NCBI Conserved Domain Search

Pleckstrin homology domain;

Pssm-ID: 465218 Cd Length: 143 Bit Score: 278.51 E-value: 1.65e-86

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1804876928 1433 VQCDGLAEQLIFNSLTNCLGPRKLLHSGKLYKTKSNKELHGFLFNDFLLLTYMVKQFAvSSGSEKLFSSKSNAQFKMYKT 1512
Cdd:pfam16652    1 VQCEGLSEQLVFNSLTNCLGPRKLLHSGKLYKVKSNKELVGFLFNDFLLLTQPVKPLS-SAGTDKLFSSKSNIQYKMYKT 79

                           90       100       110       120       130       140
                   ....*....|....*....|....*....|....*....|....*....|....*....|....
gi 1804876928 1513 PIFLNEVLVKLPTDPSSDEPVFHISHIDRVYTLRTDNINERTAWVQKIKAASEQYIDTEKKKRE 1576
Cdd:pfam16652   80 PIFLNEVMVKLPTDPSSSEPTFQLSHIDRVYTLKAESPNERTAWVKKIKEASELYIETEKKKRE 143

Intersectin Pleckstrin homology (PH) domain; ITSNs, an adaptor protein family, play a role in endo- and exocytosis, actin cytoskeleton rearrangement and signal transduction. There are two human ITSN genes: ITSN1 and ITSN2. They share significant sequence identity and a similar domain structure having both short and long isoforms produced by alternative splicing. The short isoform (ITSN-S) consists of two Eps15 homology domains (EH1 and EH2), a coiled-coil region (CCR) and five Src homology 3 domains (SH3A-E). The EH domains bind to Asn-Pro-Phe motifs and are implicated in endocytosis and vesicle transport. The SH3 domains bind to proline-rich sequences and are commonly found in proteins implicated in cell signalling pathways, cytoskeletal organization and membrane traffic. The long isoform (ITSN-L) contains three additional C-terminal domains, a Dbl homology domain (DH), a Pleckstrin homology domain (PH) and a C2 domain. The tandem DH-PH domains are present in all Dbl family of GEFs. ITSN acts specifically on Cdc42 through its DH domain with no portion of the PH domain making contact with Cdc42. This is in contrast to Dbs which requires the PH domain for full catalytic activity. The ITSN PH domain binds phosphoinositides. C2 domains are usually involved in Ca2+-dependent and Ca2+-independent phospholipid binding. There are more than 30 proteins that interact with ITSNs. ITSN-S is present in mammals, frogs, flies and nematodes, while ITSN-L is present only in vertebrates. PH domains have diverse functions, but in general are involved in targeting proteins to the appropriate cellular location or in the interaction with a binding partner. They share little sequence conservation, but all have a common fold, which is electrostatically polarized. Less than 10% of PH domains bind phosphoinositide phosphates (PIPs) with high affinity and specificity. PH domains are distinguished from other PIP-binding domains by their specific high-affinity binding to PIPs with two vicinal phosphate groups: PtdIns(3,4)P2, PtdIns(4,5)P2 or PtdIns(3,4,5)P3 which results in targeting some PH domain proteins to the plasma membrane. A few display strong specificity in lipid binding. Any specificity is usually determined by loop regions or insertions in the N-terminus of the domain, which are not conserved across all PH domains. PH domains are found in cellular signaling proteins such as serine/threonine kinase, tyrosine kinases, regulators of G-proteins, endocytotic GTPases, adaptors, as well as cytoskeletal associated molecules and in lipid associated enzymes.

Pssm-ID: 270084 Cd Length: 132 Bit Score: 243.90 E-value: 1.43e-74

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1804876928 1441 QLIFNSLTNCLGPRKLLHSGKLYKTKSNKELHGFLFNDFLLLTYMVKQFAvSSGSEKLFSSKSNAQFKMYKTPIFLNEVL 1520
Cdd:cd13264      1 QLIFNSVTNCLGPRKFLHSGKLYKAKSNKELYGFLFNDFLLLTQPIKPLG-SSGNDFVFDNKANIQYKMYKTPIFLNEVL 79

                           90       100       110       120       130
                   ....*....|....*....|....*....|....*....|....*....|...
gi 1804876928 1521 VKLPTDPSSDEPVFHISHIDRVYTLRTDNINERTAWVQKIKAASEQYIDTEKK 1573
Cdd:cd13264     80 VKLPTDPSGDEPIFHISHIDRVYTLRAESINERTAWVQKIKAASELYIETEKK 132

Guanine nucleotide exchange factor for Rho/Rac/Cdc42-like GTPases; Also called Dbl-homologous (DH) domain. It appears that PH domains invariably occur C-terminal to RhoGEF/DH domains.

Pssm-ID: 238091 [Multi-domain] Cd Length: 181 Bit Score: 164.78 E-value: 2.73e-46

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1804876928 1231 RQGYIHELIRTEERYVDDLQLVVEVFQKRMVESG-FLTEGEMALIFVNWKELIMCNTKLLKALRVRKKTGGekMPVQTIG 1309
Cdd:cd00160      1 RQEVIKELLQTERNYVRDLKLLVEVFLKPLDKELlPLSPEEVELLFGNIEEIYEFHRIFLKSLEERVEEWD--KSGPRIG 78

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1804876928 1310 DILAAELSHMQAYIRFCSCQLNGAALLQQKTDEDTEFKEFLKKLasDPRCKGMPLSSFLLKPMQRITRYPLLIRSILENT 1389
Cdd:cd00160     79 DVFLKLAPFFKIYSEYCSNHPDALELLKKLKKFNKFFQEFLEKA--ESECGRLKLESLLLKPVQRLTKYPLLLKELLKHT 156

                          170       180
                   ....*....|....*....|....*
gi 1804876928 1390 LENHVDHSSLKLALERAEELCSQVN 1414
Cdd:cd00160    157 PDGHEDREDLKKALEAIKEVASQVN 181

Guanine nucleotide exchange factor for Rho/Rac/Cdc42-like GTPases; Guanine nucleotide exchange factor for Rho/Rac/Cdc42-like GTPases Also called Dbl-homologous (DH) domain. It appears that PH domains invariably occur C-terminal to RhoGEF/DH domains. Improved coverage.

Pssm-ID: 214619 [Multi-domain] Cd Length: 180 Bit Score: 163.63 E-value: 6.43e-46

                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1804876928  1235 IHELIRTEERYVDDLQLVVEVFQKRMVESG-FLTEGEMALIFVNWKELIMCNTKLLKALRVRKKTggEKMPVQTIGDILA 1313
Cdd:smart00325    2 LKELLQTERNYVRDLKLLVEVFLKPLKKELkLLSPNELETLFGNIEEIYEFHRDFLDELEERIEE--WDDSVERIGDVFL 79

                            90       100       110       120       130       140       150       160
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1804876928  1314 AELSHMQAYIRFCSCQLNGAALLQQKtDEDTEFKEFLKKLASDPRCKGMPLSSFLLKPMQRITRYPLLIRSILENTLENH 1393
Cdd:smart00325   80 KLEEFFKIYSEYCSNHPDALELLKKL-KKNPRFQKFLKEIESSPQCRRLTLESLLLKPVQRLTKYPLLLKELLKHTPEDH 158

                           170       180
                    ....*....|....*....|..
gi 1804876928  1394 VDHSSLKLALERAEELCSQVNE 1415
Cdd:smart00325  159 EDREDLKKALKAIKELANQVNE 180

RhoGEF domain; Guanine nucleotide exchange factor for Rho/Rac/Cdc42-like GTPases Also called Dbl-homologous (DH) domain. It appears that pfam00169 domains invariably occur C-terminal to RhoGEF/DH domains.

Pssm-ID: 459876 [Multi-domain] Cd Length: 176 Bit Score: 160.54 E-value: 6.12e-45

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1804876928 1235 IHELIRTEERYVDDLQLVVEVFQKRMVESGFLTEGEMALIFVNWKELIMCNTKLLkaLRVRKKtggEKMPVQTIGDILAA 1314
Cdd:pfam00621    2 IKELLQTERSYVRDLEILVEVFLPPNSKPLSESEEEIKTIFSNIEEIYELHRQLL--LEELLK---EWISIQRIGDIFLK 76

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1804876928 1315 ELSHMQAYIRFCSCQLNGAALLQQKTDEDTEFKEFLKKLASDPRCKGMPLSSFLLKPMQRITRYPLLIRSILENTLENHV 1394
Cdd:pfam00621   77 FAPGFKVYSTYCSNYPKALKLLKKLLKKNPKFRAFLEELEANPECRGLDLNSFLIKPVQRIPRYPLLLKELLKHTPPDHP 156

                          170       180
                   ....*....|....*....|
gi 1804876928 1395 DHSSLKLALERAEELCSQVN 1414
Cdd:pfam00621  157 DYEDLKKALEAIKEVAKQIN 176

Eps15 homology domain; Pair of EF hand motifs that recognise proteins containing Asn-Pro-Phe (NPF) sequences.

Pssm-ID: 197477 [Multi-domain] Cd Length: 96 Bit Score: 132.40 E-value: 4.35e-36

                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1804876928    49 MWAITSEERTKHDKQFDSLKPSG-GYITGDQARTFFLQSGLPAPVLAEIWALSDLNKDGKMDQQEFSIAMKLIKLKLQGQ 127
Cdd:smart00027    1 PWAISPEDKAKYEQIFRSLDKNQdGTVTGAQAKPILLKSGLPQTLLAKIWNLADIDNDGELDKDEFALAMHLIYRKLNGY 80

                            90
                    ....*....|....
gi 1804876928   128 QLPVVLPPIMKQPP 141
Cdd:smart00027   81 PIPASLPPSLIPPS 94

Second Src homology 3 domain (or SH3B) of Intersectin-2; Intersectin-2 (ITSN2) is an adaptor protein that functions in exo- and endocytosis, actin cytoskeletal reorganization, and signal transduction. It plays a role in clathrin-coated pit (CCP) formation. It binds to many proteins through its multidomain structure and facilitate the assembly of multimeric complexes. ITSN2 also functions as a specific GEF for Cdc42 activation in epithelial morphogenesis, and is required in mitotic spindle orientation. It exists in alternatively spliced short and long isoforms. The short isoform contains two Eps15 homology domains (EH1 and EH2), a coiled-coil region and five SH3 domains (SH3A-E), while the long isoform, in addition, contains RhoGEF (also called Dbl-homologous or DH), Pleckstrin homology (PH) and C2 domains. The second SH3 domain (or SH3B) of ITSN2 is expected to bind protein partners, similar to ITSN1 which has been shown to bind WNK and CdGAP. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212923 [Multi-domain] Cd Length: 52 Bit Score: 127.08 E-value: 8.54e-35

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|..
gi 1804876928  923 KAQALCSWTAKKDNHLNFSKHDIITVLEQQENWWFGEVHGGRGWFPKSYVKI 974
Cdd:cd11990      1 KAQALCSWTAKKDNHLNFSKNDIITVLEQQENWWFGEVHGGRGWFPKSYVKL 52

Fourth Src homology 3 domain (or SH3D) of Intersectin-2; Intersectin-2 (ITSN2) is an adaptor protein that functions in exo- and endocytosis, actin cytoskeletal reorganization, and signal transduction. It plays a role in clathrin-coated pit (CCP) formation. It binds to many proteins through its multidomain structure and facilitate the assembly of multimeric complexes. ITSN2 also functions as a specific GEF for Cdc42 activation in epithelial morphogenesis, and is required in mitotic spindle orientation. It exists in alternatively spliced short and long isoforms. The short isoform contains two Eps15 homology domains (EH1 and EH2), a coiled-coil region and five SH3 domains (SH3A-E), while the long isoform, in addition, contains RhoGEF (also called Dbl-homologous or DH), Pleckstrin homology (PH) and C2 domains. The fourth SH3 domain (or SH3D) of ITSN2 is expected to bind protein partners, similar to ITSN1 which has been shown to bind SHIP2, Numb, CdGAP, and N-WASP. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212927 Cd Length: 59 Bit Score: 127.36 E-value: 8.68e-35

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....*....
gi 1804876928 1078 IAQVTSAYVASGSEQLSLAPGQLILILKKNSSGWWQGELQARGKKRQKGWFPASHVKLL 1136
Cdd:cd11994      1 IAQVTTAYVASGVEQLSLSPGQLILILKKNSSGWWLGELQARGKKRQKGWFPASHVKLL 59

Fifth Src homology 3 domain (or SH3E) of Intersectin-2; Intersectin-2 (ITSN2) is an adaptor protein that functions in exo- and endocytosis, actin cytoskeletal reorganization, and signal transduction. It plays a role in clathrin-coated pit (CCP) formation. It binds to many proteins through its multidomain structure and facilitate the assembly of multimeric complexes. ITSN2 also functions as a specific GEF for Cdc42 activation in epithelial morphogenesis, and is required in mitotic spindle orientation. It exists in alternatively spliced short and long isoforms. The short isoform contains two Eps15 homology domains (EH1 and EH2), a coiled-coil region and five SH3 domains (SH3A-E), while the long isoform, in addition, contains RhoGEF (also called Dbl-homologous or DH), Pleckstrin homology (PH) and C2 domains. The fifth SH3 domain (or SH3E) of ITSN2 is expected to bind protein partners, similar to ITSN1 which has been shown to bind many protein partners including SGIP1, Sos1, dynamin1/2, CIN85, c-Cbl, SHIP2, N-WASP, and synaptojanin-1, among others. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212929 [Multi-domain] Cd Length: 54 Bit Score: 126.63 E-value: 1.09e-34

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....
gi 1804876928 1151 CQVIAMYDYVANNEDELNFSKGQLINVLNKDDPDWWQGEINGVTGLFPSNYVKM 1204
Cdd:cd11996      1 CQVIAMYDYTANNEDELSFSKGQLINVLNKDDPDWWQGEINGVTGLFPSNYVKM 54

First Src homology 3 domain (or SH3A) of Intersectin-2; Intersectin-2 (ITSN2) is an adaptor protein that functions in exo- and endocytosis, actin cytoskeletal reorganization, and signal transduction. It plays a role in clathrin-coated pit (CCP) formation. It binds to many proteins through its multidomain structure and facilitate the assembly of multimeric complexes. ITSN2 also functions as a specific GEF for Cdc42 activation in epithelial morphogenesis, and is required in mitotic spindle orientation. It exists in alternatively spliced short and long isoforms. The short isoform contains two Eps15 homology domains (EH1 and EH2), a coiled-coil region and five SH3 domains (SH3A-E), while the long isoform, in addition, contains RhoGEF (also called Dbl-homologous or DH), Pleckstrin homology (PH) and C2 domains. The first SH3 domain (or SH3A) of ITSN2 is expected to bind many protein partners, similar to ITSN1 which has been shown to bind Sos1, dynamin1/2, CIN85, c-Cbl, PI3K-C2, SHIP2, N-WASP, and CdGAP, among others. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212921 [Multi-domain] Cd Length: 57 Bit Score: 125.76 E-value: 2.64e-34

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....*..
gi 1804876928  782 LVNYKALYRFEARSHDEMSFNSGDIIQVDEKTIGEPGWLYGSFQGNFGWFPCNYVEK 838
Cdd:cd11988      1 LVNYRALYPFEARNHDEMSFNAGDIIQVDEKTVGEPGWLYGSFQGNFGWFPCNYVEK 57

Third Src homology 3 domain (or SH3C) of Intersectin-2; Intersectin-2 (ITSN2) is an adaptor protein that functions in exo- and endocytosis, actin cytoskeletal reorganization, and signal transduction. It plays a role in clathrin-coated pit (CCP) formation. It binds to many proteins through its multidomain structure and facilitate the assembly of multimeric complexes. ITSN2 also functions as a specific GEF for Cdc42 activation in epithelial morphogenesis, and is required in mitotic spindle orientation. It exists in alternatively spliced short and long isoforms. The short isoform contains two Eps15 homology domains (EH1 and EH2), a coiled-coil region and five SH3 domains (SH3A-E), while the long isoform, in addition, contains RhoGEF (also called Dbl-homologous or DH), Pleckstrin homology (PH) and C2 domains. The third SH3 domain (SH3C) of ITSN2 has been shown to bind the K15 protein of Kaposi's sarcoma-associated herpesvirus. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212925 Cd Length: 52 Bit Score: 122.04 E-value: 4.78e-33

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|..
gi 1804876928 1006 EYIALYSYSSVEPGDLTFIEGEEILVTQKDGEWWTGSIGDRTGIFPSNYVKP 1057
Cdd:cd11992      1 EYIALYPYSSSEPGDLTFNEGEEILVTQKDGEWWTGSIEDRTGIFPSNYVRP 52

Fourth Src homology 3 domain (or SH3D) of Intersectin; Intersectins (ITSNs) are adaptor proteins that function in exo- and endocytosis, actin cytoskeletal reorganization, and signal transduction. They are essential for initiating clathrin-coated pit formation. They bind to many proteins through their multidomain structure and facilitate the assembly of multimeric complexes. Vertebrates contain two ITSN proteins, ITSN1 and ITSN2, which exist in alternatively spliced short and long isoforms. The short isoforms contain two Eps15 homology domains (EH1 and EH2), a coiled-coil region and five SH3 domains (SH3A-E), while the long isoforms, in addition, contain RhoGEF (also called Dbl-homologous or DH), Pleckstrin homology (PH) and C2 domains. ITSN1 and ITSN2 are both widely expressed, with variations depending on tissue type and stage of development. The fourth SH3 domain (or SH3D) of ITSN1 has been shown to bind SHIP2, Numb, CdGAP, and N-WASP. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212773 [Multi-domain] Cd Length: 58 Bit Score: 115.13 E-value: 1.61e-30

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....*...
gi 1804876928 1078 IAQVTSAYVASGSEQLSLAPGQLILILKKNSSGWWQGELQARGKKRQKGWFPASHVKL 1135
Cdd:cd11839      1 IAQVIAPFTATAENQLSLAVGQLVLVRKKSPSGWWEGELQARGKKRQIGWFPANYVKL 58

Fifth Src homology 3 domain (or SH3E) of Intersectin; Intersectins (ITSNs) are adaptor proteins that function in exo- and endocytosis, actin cytoskeletal reorganization, and signal transduction. They are essential for initiating clathrin-coated pit formation. They bind to many proteins through their multidomain structure and facilitate the assembly of multimeric complexes. Vertebrates contain two ITSN proteins, ITSN1 and ITSN2, which exist in alternatively spliced short and long isoforms. The short isoforms contain two Eps15 homology domains (EH1 and EH2), a coiled-coil region and five SH3 domains (SH3A-E), while the long isoforms, in addition, contain RhoGEF (also called Dbl-homologous or DH), Pleckstrin homology (PH) and C2 domains. ITSN1 and ITSN2 are both widely expressed, with variations depending on tissue type and stage of development. The fifth SH3 domain (or SH3E) of ITSN1 has been shown to bind many protein partners including SGIP1, Sos1, dynamin1/2, CIN85, c-Cbl, SHIP2, N-WASP, and synaptojanin-1, among others. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212774 [Multi-domain] Cd Length: 53 Bit Score: 114.82 E-value: 1.61e-30

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|...
gi 1804876928 1152 QVIAMYDYVANNEDELNFSKGQLINVLNKDDPDWWQGEINGVTGLFPSNYVKM 1204
Cdd:cd11840      1 QVIALFPYTAQNEDELSFQKGDIINVLSKDDPDWWRGELNGQTGLFPSNYVEP 53

Third Src homology 3 domain (or SH3C) of Intersectin; Intersectins (ITSNs) are adaptor proteins that function in exo- and endocytosis, actin cytoskeletal reorganization, and signal transduction. They are essential for initiating clathrin-coated pit formation. They bind to many proteins through their multidomain structure and facilitate the assembly of multimeric complexes. Vertebrates contain two ITSN proteins, ITSN1 and ITSN2, which exist in alternatively spliced short and long isoforms. The short isoforms contain two Eps15 homology domains (EH1 and EH2), a coiled-coil region and five SH3 domains (SH3A-E), while the long isoforms, in addition, contain RhoGEF (also called Dbl-homologous or DH), Pleckstrin homology (PH) and C2 domains. ITSN1 and ITSN2 are both widely expressed, with variations depending on tissue type and stage of development. The third SH3 domain (or SH3C) of ITSN1 has been shown to bind many proteins including dynamin1/2, CIN85, c-Cbl, SHIP2, Reps1, synaptojanin-1, and WNK, among others. The SH3C of ITSN2 has been shown to bind the K15 protein of Kaposi's sarcoma-associated herpesvirus. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212772 [Multi-domain] Cd Length: 52 Bit Score: 114.05 E-value: 2.93e-30

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|..
gi 1804876928 1006 EYIALYSYSSVEPGDLTFIEGEEILVTQKDGEWWTGSIGDRTGIFPSNYVKP 1057
Cdd:cd11838      1 EYIALYPYESNEPGDLTFNAGDVILVTKKDGEWWTGTIGDRTGIFPSNYVRP 52

Fourth Src homology 3 domain (or SH3D) of Intersectin-1; Intersectin-1 (ITSN1) is an adaptor protein that functions in exo- and endocytosis, actin cytoskeletal reorganization, and signal transduction. It plays a role in clathrin-coated pit (CCP) formation. It binds to many proteins through its multidomain structure and facilitate the assembly of multimeric complexes. ITSN1 localizes in membranous organelles, CCPs, the Golgi complex, and may be involved in the cell membrane trafficking system. It exists in alternatively spliced short and long isoforms. The short isoform contains two Eps15 homology domains (EH1 and EH2), a coiled-coil region and five SH3 domains (SH3A-E), while the long isoform, in addition, contains RhoGEF (also called Dbl-homologous or DH), Pleckstrin homology (PH) and C2 domains. The fourth SH3 domain (or SH3D) of ITSN1 has been shown to bind SHIP2, Numb, CdGAP, and N-WASP. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212926 Cd Length: 65 Bit Score: 112.90 E-value: 1.18e-29

                           10        20        30        40        50        60
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 1804876928 1074 KKPEIAQVTSAYVASGSEQLSLAPGQLILILKKNSSGWWQGELQARGKKRQKGWFPASHVKLLGP 1138
Cdd:cd11993      1 KKPEIAQVIASYTATGPEQLTLAPGQLILIRKKNPGGWWEGELQARGKKRQIGWFPANYVKLLSP 65

Eps15 homology domain; Pair of EF hand motifs that recognise proteins containing Asn-Pro-Phe (NPF) sequences.

Pssm-ID: 197477 [Multi-domain] Cd Length: 96 Bit Score: 112.76 E-value: 2.79e-29

                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1804876928   273 EWAVPQPSRLKYRQKFNSLDKSMSGYLSGFQARNALLQSNLSQTQLATIWTLADIDGDGQLRAEEFILAMHLTDMAKAGQ 352
Cdd:smart00027    1 PWAISPEDKAKYEQIFRSLDKNQDGTVTGAQAKPILLKSGLPQTLLAKIWNLADIDNDGELDKDEFALAMHLIYRKLNGY 80

First Src homology 3 domain (or SH3A) of Intersectin; Intersectins (ITSNs) are adaptor proteins that function in exo- and endocytosis, actin cytoskeletal reorganization, and signal transduction. They are essential for initiating clathrin-coated pit formation. They bind to many proteins through their multidomain structure and facilitate the assembly of multimeric complexes. Vertebrates contain two ITSN proteins, ITSN1 and ITSN2, which exist in alternatively spliced short and long isoforms. The short isoforms contain two Eps15 homology domains (EH1 and EH2), a coiled-coil region and five SH3 domains (SH3A-E), while the long isoforms, in addition, contain RhoGEF (also called Dbl-homologous or DH), Pleckstrin homology (PH) and C2 domains. ITSN1 and ITSN2 are both widely expressed, with variations depending on tissue type and stage of development. The first SH3 domain (or SH3A) of ITSN1 has been shown to bind many proteins including Sos1, dynamin1/2, CIN85, c-Cbl, PI3K-C2, SHIP2, N-WASP, and CdGAP, among others. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212770 [Multi-domain] Cd Length: 55 Bit Score: 110.91 E-value: 4.59e-29

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....
gi 1804876928  785 YKALYRFEARSHDEMSFNSGDIIQVDEKTIGEPGWLYGSFQGNFGWFPCNYVEK 838
Cdd:cd11836      2 YRALYAFEARNPDEISFQPGDIIQVDESQVAEPGWLAGELKGKTGWFPANYVEK 55

Fifth Src homology 3 domain (or SH3E) of Intersectin-1; Intersectin-1 (ITSN1) is an adaptor protein that functions in exo- and endocytosis, actin cytoskeletal reorganization, and signal transduction. It plays a role in clathrin-coated pit (CCP) formation. It binds to many proteins through its multidomain structure and facilitate the assembly of multimeric complexes. ITSN1 localizes in membranous organelles, CCPs, the Golgi complex, and may be involved in the cell membrane trafficking system. It exists in alternatively spliced short and long isoforms. The short isoform contains two Eps15 homology domains (EH1 and EH2), a coiled-coil region and five SH3 domains (SH3A-E), while the long isoform, in addition, contains RhoGEF (also called Dbl-homologous or DH), Pleckstrin homology (PH) and C2 domains. The fifth SH3 domain (or SH3E) of ITSN1 has been shown to bind many protein partners including SGIP1, Sos1, dynamin1/2, CIN85, c-Cbl, SHIP2, N-WASP, and synaptojanin-1, among others. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212928 [Multi-domain] Cd Length: 54 Bit Score: 106.58 E-value: 1.45e-27

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....
gi 1804876928 1151 CQVIAMYDYVANNEDELNFSKGQLINVLNKDDPDWWQGEINGVTGLFPSNYVKM 1204
Cdd:cd11995      1 CQVIGMYDYTAQNDDELAFSKGQIINVLNKEDPDWWKGELNGQVGLFPSNYVKL 54

Second Src homology 3 domain (or SH3B) of Intersectin; Intersectins (ITSNs) are adaptor proteins that function in exo- and endocytosis, actin cytoskeletal reorganization, and signal transduction. They are essential for initiating clathrin-coated pit formation. They bind to many proteins through their multidomain structure and facilitate the assembly of multimeric complexes. Vertebrates contain two ITSN proteins, ITSN1 and ITSN2, which exist in alternatively spliced short and long isoforms. The short isoforms contain two Eps15 homology domains (EH1 and EH2), a coiled-coil region and five SH3 domains (SH3A-E), while the long isoforms, in addition, contain RhoGEF (also called Dbl-homologous or DH), Pleckstrin homology (PH) and C2 domains. ITSN1 and ITSN2 are both widely expressed, with variations depending on tissue type and stage of development. The second SH3 domain (or SH3B) of ITSN1 has been shown to bind WNK and CdGAP. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212771 [Multi-domain] Cd Length: 53 Bit Score: 103.98 E-value: 1.08e-26

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|...
gi 1804876928  923 KAQALCSWTAKKDNHLNFSKHDIITVLEQQENWWFGEVHGGR-GWFPKSYVKI 974
Cdd:cd11837      1 TATALYPWRAKKENHLSFAKGDIITVLEQQEMWWFGELEGGEeGWFPKSYVKE 53

Eps15 homology domain; found in proteins implicated in endocytosis, vesicle transport, and signal transduction. The alignment contains a pair of EF-hand motifs, typically one of them is canonical and binds to Ca2+, while the other may not bind to Ca2+. A hydrophobic binding pocket is formed by residues from both EF-hand motifs. The EH domain binds to proteins containing NPF (class I), [WF]W or SWG (class II), or H[TS]F (class III) sequence motifs.

Pssm-ID: 238009 [Multi-domain] Cd Length: 67 Bit Score: 98.45 E-value: 1.40e-24

                           10        20        30        40        50        60
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 1804876928   61 DKQFDSLKPSG-GYITGDQARTFFLQSGLPAPVLAEIWALSDLNKDGKMDQQEFSIAMKLIKLKLQ 125
Cdd:cd00052      2 DQIFRSLDPDGdGLISGDEARPFLGKSGLPRSVLAQIWDLADTDKDGKLDKEEFAIAMHLIALALN 67

Eps15 homology domain; found in proteins implicated in endocytosis, vesicle transport, and signal transduction. The alignment contains a pair of EF-hand motifs, typically one of them is canonical and binds to Ca2+, while the other may not bind to Ca2+. A hydrophobic binding pocket is formed by residues from both EF-hand motifs. The EH domain binds to proteins containing NPF (class I), [WF]W or SWG (class II), or H[TS]F (class III) sequence motifs.

Pssm-ID: 238009 [Multi-domain] Cd Length: 67 Bit Score: 97.29 E-value: 3.08e-24

                           10        20        30        40        50        60
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 1804876928  284 YRQKFNSLDKSMSGYLSGFQARNALLQSNLSQTQLATIWTLADIDGDGQLRAEEFILAMHLTDMAKA 350
Cdd:cd00052      1 YDQIFRSLDPDGDGLISGDEARPFLGKSGLPRSVLAQIWDLADTDKDGKLDKEEFAIAMHLIALALN 67

Third Src homology 3 domain (or SH3C) of Intersectin-1; Intersectin-1 (ITSN1) is an adaptor protein that functions in exo- and endocytosis, actin cytoskeletal reorganization, and signal transduction. It plays a role in clathrin-coated pit (CCP) formation. It binds to many proteins through its multidomain structure and facilitate the assembly of multimeric complexes. ITSN1 localizes in membranous organelles, CCPs, the Golgi complex, and may be involved in the cell membrane trafficking system. It exists in alternatively spliced short and long isoforms. The short isoform contains two Eps15 homology domains (EH1 and EH2), a coiled-coil region and five SH3 domains (SH3A-E), while the long isoform, in addition, contains RhoGEF (also called Dbl-homologous or DH), Pleckstrin homology (PH) and C2 domains. The third SH3 domain (or SH3C) of ITSN1 has been shown to bind many proteins including dynamin1/2, CIN85, c-Cbl, SHIP2, Reps1, synaptojanin-1, and WNK, among others. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212924 Cd Length: 52 Bit Score: 94.28 E-value: 2.62e-23

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|..
gi 1804876928 1006 EYIALYSYSSVEPGDLTFIEGEEILVTQKDGEWWTGSIGDRTGIFPSNYVKP 1057
Cdd:cd11991      1 EYVAMYTYESNEQGDLTFQQGDVILVTKKDGDWWTGTVGDKTGVFPSNYVRP 52

Second Src homology 3 domain (or SH3B) of Intersectin-1; Intersectin-1 (ITSN1) is an adaptor protein that functions in exo- and endocytosis, actin cytoskeletal reorganization, and signal transduction. It plays a role in clathrin-coated pit (CCP) formation. It binds to many proteins through its multidomain structure and facilitate the assembly of multimeric complexes. ITSN1 localizes in membranous organelles, CCPs, the Golgi complex, and may be involved in the cell membrane trafficking system. It exists in alternatively spliced short and long isoforms. The short isoform contains two Eps15 homology domains (EH1 and EH2), a coiled-coil region and five SH3 domains (SH3A-E), while the long isoform, in addition, contains RhoGEF (also called Dbl-homologous or DH), Pleckstrin homology (PH) and C2 domains. The second SH3 domain (or SH3B) of ITSN1 has been shown to bind WNK and CdGAP. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212922 [Multi-domain] Cd Length: 52 Bit Score: 92.47 E-value: 1.07e-22

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|..
gi 1804876928  923 KAQALCSWTAKKDNHLNFSKHDIITVLEQQENWWFGEVHGGRGWFPKSYVKI 974
Cdd:cd11989      1 QAQALYPWRAKKDNHLNFNKNDVITVLEQQDMWWFGEVQGQKGWFPKSYVKL 52

First Src homology 3 domain (or SH3A) of Intersectin-1; Intersectin-1 (ITSN1) is an adaptor protein that functions in exo- and endocytosis, actin cytoskeletal reorganization, and signal transduction. It plays a role in clathrin-coated pit (CCP) formation. It binds to many proteins through its multidomain structure and facilitate the assembly of multimeric complexes. ITSN1 localizes in membranous organelles, CCPs, the Golgi complex, and may be involved in the cell membrane trafficking system. It exists in alternatively spliced short and long isoforms. The short isoform contains two Eps15 homology domains (EH1 and EH2), a coiled-coil region and five SH3 domains (SH3A-E), while the long isoform, in addition, contains RhoGEF (also called Dbl-homologous or DH), Pleckstrin homology (PH) and C2 domains. The first SH3 domain (or SH3A) of ITSN1 has been shown to bind many proteins including Sos1, dynamin1/2, CIN85, c-Cbl, PI3K-C2, SHIP2, N-WASP, and CdGAP, among others. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212920 [Multi-domain] Cd Length: 55 Bit Score: 88.13 E-value: 4.13e-21

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....
gi 1804876928  785 YKALYRFEARSHDEMSFNSGDIIQVDEKTIGEPGWLYGSFQGNFGWFPCNYVEK 838
Cdd:cd11987      2 YRALYPFEARSHDEITIQPGDIVMVDESQTGEPGWLGGELKGKTGWFPANYAEK 55

Src homology 3 domains; Src homology 3 (SH3) domains bind to target proteins through sequences containing proline and hydrophobic amino acids. Pro-containing polypeptides may bind to SH3 domains in 2 different binding orientations.

Pssm-ID: 214620 [Multi-domain] Cd Length: 56 Bit Score: 86.44 E-value: 1.65e-20

                            10        20        30        40        50
                    ....*....|....*....|....*....|....*....|....*....|....*.
gi 1804876928  1149 PVCQVIAMYDYVANNEDELNFSKGQLINVLNKDDPDWWQGEIN-GVTGLFPSNYVK 1203
Cdd:smart00326    1 EGPQVRALYDYTAQDPDELSFKKGDIITVLEKSDDGWWKGRLGrGKEGLFPSNYVE 56

Src Homology 3 domain superfamily; Src Homology 3 (SH3) domains are protein interaction domains that bind proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. Thus, they are referred to as proline-recognition domains (PRDs). SH3 domains are less selective and show more diverse specificity compared to other PRDs. They have been shown to bind peptide sequences that lack the PxxP motif; examples include the PxxDY motif of Eps8 and the RKxxYxxY sequence in SKAP55. SH3 domain containing proteins play versatile and diverse roles in the cell, including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies, among others. Many members of this superfamily are adaptor proteins that associate with a number of protein partners, facilitating complex formation and signal transduction.

Pssm-ID: 212690 [Multi-domain] Cd Length: 51 Bit Score: 83.28 E-value: 2.08e-19

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|.
gi 1804876928 1152 QVIAMYDYVANNEDELNFSKGQLINVLNKDDPDWWQGEIN-GVTGLFPSNY 1201
Cdd:cd00174      1 YARALYDYEAQDDDELSFKKGDIITVLEKDDDGWWEGELNgGREGLFPANY 51

Src homology 3 domain of Abl Interactor proteins; Abl interactor (Abi) proteins are adaptor proteins serving as binding partners and substrates of Abl tyrosine kinases. They are involved in regulating actin cytoskeletal reorganization and play important roles in membrane-ruffling, endocytosis, cell motility, and cell migration. They localize to sites of actin polymerization in epithelial adherens junction and immune synapses, as well as to the leading edge of lamellipodia. Vertebrates contain two Abi proteins, Abi1 and Abi2. Abi1 displays a wide expression pattern while Abi2 is highly expressed in the eye and brain. Abi proteins contain a homeobox homology domain, a proline-rich region, and a SH3 domain. The SH3 domain of Abi binds to a PxxP motif in Abl. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212760 [Multi-domain] Cd Length: 52 Bit Score: 81.98 E-value: 5.10e-19

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|
gi 1804876928 1153 VIAMYDYVANNEDELNFSKGQLINVLNKDDPDWWQGEINGVTGLFPSNYV 1202
Cdd:cd11826      2 VVALYDYTADKDDELSFQEGDIIYVTKKNDDGWYEGVLNGVTGLFPGNYV 51

C-terminal Src homology 3 domain of Growth factor receptor-bound protein 2 (GRB2) and related proteins; This family includes the adaptor protein GRB2 and related proteins including Drosophila melanogaster Downstream of receptor kinase (DRK), Caenorhabditis elegans Sex muscle abnormal protein 5 (Sem-5), GRB2-related adaptor protein (GRAP), GRAP2, and similar proteins. Family members contain an N-terminal SH3 domain, a central SH2 domain, and a C-terminal SH3 domain. GRB2/Sem-5/DRK is a critical signaling molecule that regulates the Ras pathway by linking tyrosine kinases to the Ras guanine nucleotide releasing protein Sos (son of sevenless), which converts Ras to the active GTP-bound state. GRAP2 plays an important role in T cell receptor (TCR) signaling by promoting the formation of the SLP-76:LAT complex, which couples the TCR to the Ras pathway. GRAP acts as a negative regulator of T cell receptor (TCR)-induced lymphocyte proliferation by downregulating the signaling to the Ras/ERK pathway. The C-terminal SH3 domains (SH3c) of GRB2 and GRAP2 have been shown to bind to classical PxxP motif ligands, as well as to non-classical motifs. GRB2 SH3c binds Gab2 (Grb2-associated binder 2) through epitopes containing RxxK motifs, while the SH3c of GRAP2 binds to the phosphatase-like protein HD-PTP via a RxxxxK motif. SH3 domains are protein interaction domains that typically bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212739 [Multi-domain] Cd Length: 53 Bit Score: 80.36 E-value: 2.16e-18

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|..
gi 1804876928 1152 QVIAMYDYVANNEDELNFSKGQLINVLNKDDPDWWQGEINGVTGLFPSNYVK 1203
Cdd:cd11805      1 RVQALYDFNPQEPGELEFRRGDIITVLDSSDPDWWKGELRGRVGIFPANYVQ 52

Src homology 3 domain of Nitric Oxide Synthase TRaffic INducer; Nostrin is expressed in endothelial and epithelial cells and is involved in the regulation, trafficking and targeting of endothelial NOS (eNOS). It facilitates the endocytosis of eNOS by coordinating the functions of dynamin and the Wiskott-Aldrich syndrome protein (WASP). Increased expression of Nostrin may be correlated to preeclampsia. Nostrin contains an N-terminal F-BAR domain and a C-terminal SH3 domain. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212757 [Multi-domain] Cd Length: 53 Bit Score: 77.00 E-value: 3.15e-17

                           10        20        30        40
                   ....*....|....*....|....*....|....*....|....*...
gi 1804876928 1155 AMYDYVANNEDELNFSKGQLINVLNKDDPDWWQGEINGVTGLFPSNYV 1202
Cdd:cd11823      4 ALYSYTANREDELSLQPGDIIEVHEKQDDGWWLGELNGKKGIFPATYV 51

Src Homology 3 domain of Pak Interactive eXchange factors; PIX proteins are Rho guanine nucleotide exchange factors (GEFs), which activate small GTPases by exchanging bound GDP for free GTP. They act as GEFs for both Cdc42 and Rac 1, and have been implicated in cell motility, adhesion, neurite outgrowth, and cell polarity. Vertebrates contain two proteins from the PIX subfamily, alpha-PIX and beta-PIX. Alpha-PIX, also called ARHGEF6, is localized in dendritic spines where it regulates spine morphogenesis. Mutations in the ARHGEF6 gene cause X-linked intellectual disability in humans. Beta-PIX play roles in regulating neuroendocrine exocytosis, focal adhesion maturation, cell migration, synaptic vesicle localization, and insulin secretion. PIX proteins contain an N-terminal SH3 domain followed by RhoGEF (also called Dbl-homologous or DH) and Pleckstrin Homology (PH) domains, and a C-terminal leucine-zipper domain for dimerization. The SH3 domain of PIX binds to an atypical PxxxPR motif in p21-activated kinases (PAKs) with high affinity. The binding of PAKs to PIX facilitate the localization of PAKs to focal complexes and also localizes PAKs to PIX targets Cdc43 and Rac, leading to the activation of PAKs. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212810 [Multi-domain] Cd Length: 53 Bit Score: 73.89 E-value: 4.35e-16

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|..
gi 1804876928 1152 QVIAMYDYVANNEDELNFSKGQLINVLNKDDPDWWQGEINGVTGLFPSNYVK 1203
Cdd:cd11877      1 LVRAKFNFEGTNEDELSFDKGDIITVTQVVEGGWWEGTLNGKTGWFPSNYVK 52

Variant SH3 domain;

Pssm-ID: 434066 [Multi-domain] Cd Length: 49 Bit Score: 72.26 E-value: 1.27e-15

                           10        20        30        40
                   ....*....|....*....|....*....|....*....|....*....
gi 1804876928 1155 AMYDYVANNEDELNFSKGQLINVLNKDDPDWWQGEINGVTGLFPSNYVK 1203
Cdd:pfam14604    1 ALYPYEPKDDDELSLQRGDVITVIEESEDGWWEGINTGRTGLVPANYVE 49

N-terminal Src homology 3 domain of Growth factor receptor-bound protein 2 (GRB2) and related proteins; This family includes the adaptor protein GRB2 and related proteins including Drosophila melanogaster Downstream of receptor kinase (DRK), Caenorhabditis elegans Sex muscle abnormal protein 5 (Sem-5), GRB2-related adaptor protein (GRAP), GRAP2, and similar proteins. Family members contain an N-terminal SH3 domain, a central SH2 domain, and a C-terminal SH3 domain. GRB2/Sem-5/DRK is a critical signaling molecule that regulates the Ras pathway by linking tyrosine kinases to the Ras guanine nucleotide releasing protein Sos (son of sevenless), which converts Ras to the active GTP-bound state. GRAP2 plays an important role in T cell receptor (TCR) signaling by promoting the formation of the SLP-76:LAT complex, which couples the TCR to the Ras pathway. GRAP acts as a negative regulator of T cell receptor (TCR)-induced lymphocyte proliferation by downregulating the signaling to the Ras/ERK pathway. The N-terminal SH3 domain of GRB2 binds to Sos and Sos-derived proline-rich peptides. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212738 [Multi-domain] Cd Length: 52 Bit Score: 72.39 E-value: 1.33e-15

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|
gi 1804876928 1154 IAMYDYVANNEDELNFSKGQLINVLNKD-DPDWWQGEINGVTGLFPSNYV 1202
Cdd:cd11804      3 VAKHDFKATAEDELSFKKGSILKVLNMEdDPNWYKAELDGKEGLIPKNYI 52

Third Src Homology 3 domain (SH3C) of CD2-associated protein and similar proteins; This subfamily is composed of the third SH3 domain (SH3C) of CD2AP, CIN85 (Cbl-interacting protein of 85 kDa), and similar domains. CD2AP and CIN85 are adaptor proteins that bind to protein partners and assemble complexes that have been implicated in T cell activation, kidney function, and apoptosis of neuronal cells. They also associate with endocytic proteins, actin cytoskeleton components, and other adaptor proteins involved in receptor tyrosine kinase (RTK) signaling. CD2AP and the main isoform of CIN85 contain three SH3 domains, a proline-rich region, and a C-terminal coiled-coil domain. All of these domains enable CD2AP and CIN85 to bind various protein partners and assemble complexes that have been implicated in many different functions. SH3C of both proteins have been shown to bind to ubiquitin. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212808 [Multi-domain] Cd Length: 55 Bit Score: 71.61 E-value: 2.58e-15

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|.
gi 1804876928 1155 AMYDYVANNEDELNFSKGQLINVLNKD--DPDWWQGEINGVTGLFPSNYVK 1203
Cdd:cd11875      4 VLFDYEAENEDELTLREGDIVTILSKDceDKGWWKGELNGKRGVFPDNFVE 54

Src homology 3 domains; Src homology 3 (SH3) domains bind to target proteins through sequences containing proline and hydrophobic amino acids. Pro-containing polypeptides may bind to SH3 domains in 2 different binding orientations.

Pssm-ID: 214620 [Multi-domain] Cd Length: 56 Bit Score: 71.42 E-value: 2.90e-15

                            10        20        30        40        50
                    ....*....|....*....|....*....|....*....|....*....|....
gi 1804876928   785 YKALYRFEARSHDEMSFNSGDIIQVDEKTigEPGWLYGSFQ-GNFGWFPCNYVE 837
Cdd:smart00326    5 VRALYDYTAQDPDELSFKKGDIITVLEKS--DDGWWKGRLGrGKEGLFPSNYVE 56

Src Homology 3 domain of SH3 domain-containing protein 21 (SH3D21) and similar proteins; N-terminal SH3 domain of the uncharacterized protein SH3 domain-containing protein 21, and similar uncharacterized domains, it belongs to the CD2AP-like_3 subfamily of proteins. The CD2AP-like_3 subfamily is composed of the third SH3 domain (SH3C) of CD2AP, CIN85 (Cbl-interacting protein of 85 kDa), and similar domains. CD2AP and CIN85 are adaptor proteins that bind to protein partners and assemble complexes that have been implicated in T cell activation, kidney function, and apoptosis of neuronal cells. They also associate with endocytic proteins, actin cytoskeleton components, and other adaptor proteins involved in receptor tyrosine kinase (RTK) signaling. CD2AP and the main isoform of CIN85 contain three SH3 domains, a proline-rich region, and a C-terminal coiled-coil domain. All of these domains enable CD2AP and CIN85 to bind various protein partners and assemble complexes that have been implicated in many different functions. SH3C of both proteins have been shown to bind to ubiquitin. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 213018 [Multi-domain] Cd Length: 55 Bit Score: 71.34 E-value: 3.36e-15

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....*..
gi 1804876928 1150 VCQViaMYDYVANNEDELNFSKGQLINVLNKDDPD--WWQGEINGVTGLFPSNYVKM 1204
Cdd:cd12142      1 YCRV--LFDYNPVAPDELALKKGDVIEVISKETEDegWWEGELNGRRGFFPDNFVMP 55

Src homology 3 domain of Abl Interactor 2; Abi2 is highly expressed in the brain and eye. It regulates actin cytoskeletal reorganization at adherens junctions and dendritic spines, which is important in cell morphogenesis, migration, and cognitive function. Mice deficient with Abi2 show defects in orientation and migration of lens fibers, neuronal migration, dendritic spine morphology, as well as deficits in learning and memory. Abi proteins are adaptor proteins serving as binding partners and substrates of Abl tyrosine kinases. They are involved in regulating actin cytoskeletal reorganization and play important roles in membrane-ruffling, endocytosis, cell motility, and cell migration. Abi proteins contain a homeobox homology domain, a proline-rich region, and a SH3 domain. The SH3 domain of Abi binds to a PxxP motif in Abl. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212905 [Multi-domain] Cd Length: 61 Bit Score: 71.19 E-value: 4.75e-15

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|..
gi 1804876928 1152 QVIAMYDYVANNEDELNFSKGQLINVLNKDDPDWWQGEINGVTGLFPSNYVK 1203
Cdd:cd11972      4 KVVAIYDYTKDKEDELSFQEGAIIYVIKKNDDGWYEGVMNGVTGLFPGNYVE 55

Src Homology 3 domain of Abelson helper integration site-1 (AHI-1); AHI-1, also called Jouberin, is expressed in high levels in the brain, gonad tissues, and skeletal muscle. It is an adaptor protein that interacts with the small GTPase Rab8a and regulates it distribution and function, affecting cilium formation and vesicle transport. Mutations in the AHI-1 gene can cause Joubert syndrome, a disorder characterized by brainstem malformations, cerebellar aplasia/hypoplasia, and retinal dystrophy. AHI-1 variation is also associated with susceptibility to schizophrenia and type 2 diabetes mellitus progression. AHI-1 contains WD40 and SH3 domains. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212746 [Multi-domain] Cd Length: 52 Bit Score: 70.62 E-value: 4.90e-15

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|.
gi 1804876928 1153 VIAMYDYVANNEDELNFSKGQLINVLNKDDPDWWQGEI-NGVTGLFPSNYV 1202
Cdd:cd11812      2 VVALYDYTANRSDELTIHRGDIIRVLYKDNDNWWFGSLvNGQQGYFPANYV 52

Src homology 3 domain of Ysc84p and similar fungal proteins; This family is composed of the Saccharomyces cerevisiae proteins, Ysc84p (also called LAS17-binding protein 4, Lsb4p) and Lsb3p, and similar fungal proteins. They contain an N-terminal SYLF domain (also called DUF500) and a C-terminal SH3 domain. Ysc84p localizes to actin patches and plays an important in actin polymerization during endocytosis. The N-terminal domain of both Ysc84p and Lsb3p can bind and bundle actin filaments. A study of the yeast SH3 domain interactome predicts that the SH3 domains of Lsb3p and Lsb4p may function as molecular hubs for the assembly of endocytic complexes. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212776 [Multi-domain] Cd Length: 55 Bit Score: 70.15 E-value: 8.73e-15

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|..
gi 1804876928 1008 IALYSYSSVEPGDLTFIEGEEILVTQKDG---EWWTGSIGDRTGIFPSNYVK 1056
Cdd:cd11842      3 VALYDFAGEQPGDLAFQKGDIITILKKSDsqnDWWTGRIGGREGIFPANYVE 54

SH3 domain; SH3 (Src homology 3) domains are often indicative of a protein involved in signal transduction related to cytoskeletal organization. First described in the Src cytoplasmic tyrosine kinase. The structure is a partly opened beta barrel.

Pssm-ID: 394975 [Multi-domain] Cd Length: 47 Bit Score: 69.54 E-value: 1.08e-14

                           10        20        30        40
                   ....*....|....*....|....*....|....*....|....*..
gi 1804876928 1154 IAMYDYVANNEDELNFSKGQLINVLNKDDPDWWQGE-INGVTGLFPS 1199
Cdd:pfam00018    1 VALYDYTAQEPDELSFKKGDIIIVLEKSEDGWWKGRnKGGKEGLIPS 47

Src homology 3 domain of Signal Transducing Adaptor Molecule 1; STAM1 is part of the endosomal sorting complex required for transport (ESCRT-0) and is involved in sorting ubiquitinated cargo proteins from the endosome. It may also be involved in the regulation of IL2 and GM-CSF mediated signaling, and has been implicated in neural cell survival. STAMs were discovered as proteins that are highly phosphorylated following cytokine and growth factor stimulation. They function in cytokine signaling and surface receptor degradation, as well as regulate Golgi morphology. They associate with many proteins including Jak2 and Jak3 tyrosine kinases, Hrs, AMSH, and UBPY. STAM adaptor proteins contain VHS (Vps27, Hrs, STAM homology), ubiquitin interacting (UIM), and SH3 domains. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212897 [Multi-domain] Cd Length: 55 Bit Score: 69.98 E-value: 1.14e-14

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....*.
gi 1804876928 1152 QVIAMYDYVANNEDELNFSKGQLINVLNKDDPDWWQGEINGVTGLFPSNYVkmTTD 1207
Cdd:cd11964      2 KVRAIYDFEAAEDNELTFKAGDIITILDDSDPNWWKGETPQGTGLFPSNFV--TAD 55

MAEBL; Provisional

Pssm-ID: 173412 [Multi-domain] Cd Length: 2084 Bit Score: 80.19 E-value: 1.19e-14

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1804876928  382 SYQKIQEEEPQKKLpvtfEDKRKANYERGNVELEKRRQALMEQQQREAERKAQKEKEEWERKQRELQEQEWKKQLELEKR 461
Cdd:PTZ00121  1298 AEEKKKADEAKKKA----EEAKKADEAKKKAEEAKKKADAAKKKAEEAKKAAEAAKAEAEAAADEAEAAEEKAEAAEKKK 1373

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1804876928  462 LEKQRELERQREEERRKEIERREAAKQELERQR-----RLEWERIRRQELlnqrNREQEEIVRLNSKKKSLHLELEALNG 536
Cdd:PTZ00121  1374 EEAKKKADAAKKKAEEKKKADEAKKKAEEDKKKadelkKAAAAKKKADEA----KKKAEEKKKADEAKKKAEEAKKADEA 1449

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1804876928  537 KHQQISGRLQDVRLRKQTQKTEIEVLDKQCD--LEIMEIKQLQQELQDYQNKLIYLVPEKQLLNERIKNMQLGNTPDLGI 614
Cdd:PTZ00121  1450 KKKAEEAKKAEEAKKKAEEAKKADEAKKKAEeaKKADEAKKKAEEAKKKADEAKKAAEAKKKADEAKKAEEAKKADEAKK 1529

                          250       260       270       280       290       300       310       320
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1804876928  615 DLLHKKS--LEKEELCQRLKEQLDALEKETASKLSEMDSFNNQLKCGNMDDSVLQCLLSLLSCLNNLFLLLKELRESYNT 692
Cdd:PTZ00121  1530 AEEAKKAdeAKKAEEKKKADELKKAEELKKAEEKKKAEEAKKAEEDKNMALRKAEEAKKAEEARIEEVMKLYEEEKKMKA 1609

                          330       340       350       360       370       380       390       400
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1804876928  693 QQLALEQLHKIKRDKLKEIERKRSELIQKKKLEDEAIRKAKQGKENLWRESLRKEEEEKQKRLQEEKTQE--KVQEEERK 770
Cdd:PTZ00121  1610 EEAKKAEEAKIKAEELKKAEEEKKKVEQLKKKEAEEKKKAEELKKAEEENKIKAAEEAKKAEEDKKKAEEakKAEEDEKK 1689


                   ....
gi 1804876928  771 VEEK 774
Cdd:PTZ00121  1690 AAEA 1693

chromosome segregation protein SMC, common bacterial type; SMC (structural maintenance of chromosomes) proteins bind DNA and act in organizing and segregating chromosomes for partition. SMC proteins are found in bacteria, archaea, and eukaryotes. This family represents the SMC protein of most bacteria. The smc gene is often associated with scpB (TIGR00281) and scpA genes, where scp stands for segregation and condensation protein. SMC was shown (in Caulobacter crescentus) to be induced early in S phase but present and bound to DNA throughout the cell cycle. [Cellular processes, Cell division, DNA metabolism, Chromosome-associated proteins]

Pssm-ID: 274008 [Multi-domain] Cd Length: 1179 Bit Score: 80.10 E-value: 1.22e-14

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1804876928  488 QELERQrrleWERIRRQ-----ELLNQRNREQE--------EIVRLNSKKKSLHLELEALNGKHQQISGRLQDVRLRKQT 554
Cdd:TIGR02168  196 NELERQ----LKSLERQaekaeRYKELKAELRElelallvlRLEELREELEELQEELKEAEEELEELTAELQELEEKLEE 271

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1804876928  555 QKTEIEVLDKqcdleimEIKQLQQELQDYQNKLIYLVPEKQLLNERIKNMQLGNTP-DLGIDLLHKKSLEKEELCQRLKE 633
Cdd:TIGR02168  272 LRLEVSELEE-------EIEELQKELYALANEISRLEQQKQILRERLANLERQLEElEAQLEELESKLDELAEELAELEE 344

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1804876928  634 QLDALEKETASKLSEMDSFNNQLKcgNMDDSVLQCLLSLLSCLNNLFLLLKELRESYNTQQLALEQLHKIKRDKLKEIER 713
Cdd:TIGR02168  345 KLEELKEELESLEAELEELEAELE--ELESRLEELEEQLETLRSKVAQLELQIASLNNEIERLEARLERLEDRRERLQQE 422

                          250       260       270       280       290       300       310
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|.
gi 1804876928  714 KRSELIQKKKLEDEAIRKA----KQGKENLWRESLRKEEEEKQKRLQEEKTQEKVQEEERKVEEKQCEPAS 780
Cdd:TIGR02168  423 IEELLKKLEEAELKELQAEleelEEELEELQEELERLEEALEELREELEEAEQALDAAERELAQLQARLDS 493

Src homology 3 domains; Src homology 3 (SH3) domains bind to target proteins through sequences containing proline and hydrophobic amino acids. Pro-containing polypeptides may bind to SH3 domains in 2 different binding orientations.

Pssm-ID: 214620 [Multi-domain] Cd Length: 56 Bit Score: 69.87 E-value: 1.23e-14

                            10        20        30        40        50
                    ....*....|....*....|....*....|....*....|....*....|...
gi 1804876928   923 KAQALCSWTAKKDNHLNFSKHDIITVLEQQE-NWWFGEVHGGR-GWFPKSYVK 973
Cdd:smart00326    4 QVRALYDYTAQDPDELSFKKGDIITVLEKSDdGWWKGRLGRGKeGLFPSNYVE 56

Src homology 3 domains; Src homology 3 (SH3) domains bind to target proteins through sequences containing proline and hydrophobic amino acids. Pro-containing polypeptides may bind to SH3 domains in 2 different binding orientations.

Pssm-ID: 214620 [Multi-domain] Cd Length: 56 Bit Score: 69.49 E-value: 1.41e-14

                            10        20        30        40        50
                    ....*....|....*....|....*....|....*....|....*....|....*.
gi 1804876928  1003 VGDEYIALYSYSSVEPGDLTFIEGEEILVTQK-DGEWWTGSIGD-RTGIFPSNYVK 1056
Cdd:smart00326    1 EGPQVRALYDYTAQDPDELSFKKGDIITVLEKsDDGWWKGRLGRgKEGLFPSNYVE 56

C-terminal Src homology 3 domain of GRB2-related adaptor protein; GRAP is a GRB-2 like adaptor protein that is highly expressed in lymphoid tissues. It acts as a negative regulator of T cell receptor (TCR)-induced lymphocyte proliferation by downregulating the signaling to the Ras/ERK pathway. It has been identified as a regulator of TGFbeta signaling in diabetic kidney tubules and may have a role in the pathogenesis of the disease. GRAP contains an N-terminal SH3 domain, a central SH2 domain, and a C-terminal SH3 domain. The C-terminal SH3 domains (SH3c) of the related proteins, GRB2 and GRAP2, have been shown to bind to classical PxxP motif ligands, as well as to non-classical motifs. GRB2 SH3c binds Gab2 (Grb2-associated binder 2) through epitopes containing RxxK motifs, while the SH3c of GRAP2 binds to the phosphatase-like protein HD-PTP via a RxxxxK motif. SH3 domains are protein interaction domains that typically bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212884 Cd Length: 53 Bit Score: 69.06 E-value: 1.87e-14

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|
gi 1804876928 1153 VIAMYDYVANNEDELNFSKGQLINVLNKDDPDWWQGEINGVTGLFPSNYV 1202
Cdd:cd11951      2 VQAQYDFSAEDPSQLSFRRGDIIEVLDCPDPNWWRGRISGRVGFFPRNYV 51

Chromosome segregation ATPase Smc [Cell cycle control, cell division, chromosome partitioning];

Pssm-ID: 440809 [Multi-domain] Cd Length: 983 Bit Score: 78.83 E-value: 2.18e-14

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1804876928  413 ELEKRRQALmeqqQREAErKAqkekeeweRKQRELQEQEwkKQLELEKRLekqrelerqreeerrkeierreaakqeler 492
Cdd:COG1196    197 ELERQLEPL----ERQAE-KA--------ERYRELKEEL--KELEAELLL------------------------------ 231

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1804876928  493 qRRLEWERIRRQELLNQRNREQEEIVRLNSKKKSLHLELEALNGKHQQISGRLQDVRLRKQTQKTEIEVLDKQCDLEIME 572
Cdd:COG1196    232 -LKLRELEAELEELEAELEELEAELEELEAELAELEAELEELRLELEELELELEEAQAEEYELLAELARLEQDIARLEER 310

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1804876928  573 IKQLQQELQDYQNKLIYLVPEKQLLNERIKNMQlgntpdLGIDLLHKKSLEKEELCQRLKEQLDALEKETASKLSEMDSF 652
Cdd:COG1196    311 RRELEERLEELEEELAELEEELEELEEELEELE------EELEEAEEELEEAEAELAEAEEALLEAEAELAEAEEELEEL 384

                          250       260       270       280       290       300       310       320
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1804876928  653 NNQlkcgnmddsvlqcllsllsclnnlflLLKELRESYNTQQlALEQLHKIKRDKLKEIERKRSELIQkkklEDEAIRKA 732
Cdd:COG1196    385 AEE--------------------------LLEALRAAAELAA-QLEELEEAEEALLERLERLEEELEE----LEEALAEL 433

                          330       340       350       360
                   ....*....|....*....|....*....|....*....|...
gi 1804876928  733 KQGKENLwRESLRKEEEEKQKRLQEEKTQEKVQEEERKVEEKQ 775
Cdd:COG1196    434 EEEEEEE-EEALEEAAEEEAELEEEEEALLELLAELLEEAALL 475

Src homology 3 domain of Signal Transducing Adaptor Molecules; STAMs were discovered as proteins that are highly phosphorylated following cytokine and growth factor stimulation. They function in cytokine signaling and surface receptor degradation, as well as regulate Golgi morphology. They associate with many proteins including Jak2 and Jak3 tyrosine kinases, Hrs, AMSH, and UBPY. STAM adaptor proteins contain VHS (Vps27, Hrs, STAM homology), ubiquitin interacting (UIM), and SH3 domains. There are two vertebrate STAMs, STAM1 and STAM2, which may be functionally redundant; vertebrate STAMs contain ITAM motifs. They are part of the endosomal sorting complex required for transport (ESCRT-0). STAM2 deficiency in mice did not cause any obvious abnormality, while STAM1 deficiency resulted in growth retardation. Loss of both STAM1 and STAM2 in mice proved lethal, indicating that STAMs are important for embryonic development. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212754 [Multi-domain] Cd Length: 54 Bit Score: 69.03 E-value: 2.19e-14

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|..
gi 1804876928 1152 QVIAMYDYVANNEDELNFSKGQLINVLNKDDPDWWQGEINGVTGLFPSNYVK 1203
Cdd:cd11820      2 KVRALYDFEAAEDNELTFKAGEIITVLDDSDPNWWKGSNHRGEGLFPANFVT 53

Variant SH3 domain; SH3 (Src homology 3) domains are often indicative of a protein involved in signal transduction related to cytoskeletal organization. First described in the Src cytoplasmic tyrosine kinase. The structure is a partly opened beta barrel.

Pssm-ID: 429575 [Multi-domain] Cd Length: 54 Bit Score: 68.78 E-value: 2.40e-14

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|.
gi 1804876928 1153 VIAMYDYVANNEDELNFSKGQLINVLNKDDPDWWQGEINGVTGLFPSNYVK 1203
Cdd:pfam07653    2 GRVIFDYVGTDKNGLTLKKGDVVKVLGKDNDGWWEGETGGRVGLVPSTAVE 52

C-terminal Src homology 3 domain of GRB2-related adaptor protein 2; GRAP2 is also called GADS (GRB2-related adapter downstream of Shc), GrpL, GRB2L, Mona, or GRID (Grb2-related protein with insert domain). It is expressed specifically in the hematopoietic system. It plays an important role in T cell receptor (TCR) signaling by promoting the formation of the SLP-76:LAT complex, which couples the TCR to the Ras pathway. It also has roles in antigen-receptor and tyrosine kinase mediated signaling. GRAP2 is unique from other GRB2-like adaptor proteins in that it can be regulated by caspase cleavage. It contains an N-terminal SH3 domain, a central SH2 domain, and a C-terminal SH3 domain. The C-terminal SH3 domain of GRAP2 binds to different motifs found in substrate peptides including the typical PxxP motif in hematopoietic progenitor kinase 1 (HPK1), the RxxK motif in SLP-76 and HPK1, and the RxxxxK motif in phosphatase-like protein HD-PTP. SH3 domains are protein interaction domains that typically bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212883 [Multi-domain] Cd Length: 53 Bit Score: 68.31 E-value: 3.14e-14

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|..
gi 1804876928 1152 QVIAMYDYVANNEDELNFSKGQLINVLNKDDPDWWQGEINGVTGLFPSNYVK 1203
Cdd:cd11950      1 QVRALYDFEALEDDELGFNSGDVIEVLDSSNPSWWKGRLHGKLGLFPANYVA 52

Second Src Homology 3 domain (SH3B) of CD2-associated protein and similar proteins; This subfamily is composed of the second SH3 domain (SH3B) of CD2AP, CIN85 (Cbl-interacting protein of 85 kDa), and similar domains. CD2AP and CIN85 are adaptor proteins that bind to protein partners and assemble complexes that have been implicated in T cell activation, kidney function, and apoptosis of neuronal cells. They also associate with endocytic proteins, actin cytoskeleton components, and other adaptor proteins involved in receptor tyrosine kinase (RTK) signaling. CD2AP and the main isoform of CIN85 contain three SH3 domains, a proline-rich region, and a C-terminal coiled-coil domain. All of these domains enable CD2AP and CIN85 to bind various protein partners and assemble complexes that have been implicated in many different functions. SH3B of both proteins have been shown to bind to Cbl. In the case of CD2AP, its SH3B binds to Cbl at a site distinct from the c-Cbl/SH3A binding site. The CIN85 SH3B also binds ubiquitin. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212807 [Multi-domain] Cd Length: 53 Bit Score: 68.51 E-value: 3.43e-14

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....
gi 1804876928 1151 CQVIamYDYVANNEDELNFSKGQLINVLNKDDPDWWQGEINGVTGLFPSNYVKM 1204
Cdd:cd11874      2 CKVL--FSYTPQNEDELELKVGDTIEVLGEVEEGWWEGKLNGKVGVFPSNFVKE 53

Second Src Homology 3 domain of Nck adaptor proteins; Nck adaptor proteins regulate actin cytoskeleton dynamics by linking proline-rich effector molecules to protein tyrosine kinases and phosphorylated signaling intermediates. They contain three SH3 domains and a C-terminal SH2 domain. They function downstream of the PDGFbeta receptor and are involved in Rho GTPase signaling and actin dynamics. Vertebrates contain two Nck adaptor proteins: Nck1 (also called Nckalpha) and Nck2 (also called Nckbeta or Growth factor receptor-bound protein 4, Grb4), which show partly overlapping functions but also bind distinct targets. Their SH3 domains are involved in recruiting downstream effector molecules, such as the N-WASP/Arp2/3 complex, which when activated induces actin polymerization that results in the production of pedestals, or protrusions of the plasma membrane. The second SH3 domain of Nck appears to prefer ligands containing the APxxPxR motif. SH3 domains are protein interaction domains that usually bind to proline-rich ligands with moderate affinity and selectivity, preferentially a PxxP motif. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212700 [Multi-domain] Cd Length: 53 Bit Score: 68.45 E-value: 3.63e-14

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|.
gi 1804876928 1152 QVIAMYDYVANNEDELNFSKGQLINVLNKDDPDWWQGEINGVTGLFPSNYV 1202
Cdd:cd11766      1 PAVVKFNYEAQREDELSLRKGDRVLVLEKSSDGWWRGECNGQVGWFPSNYV 51

Src Homology 3 domain of metazoan osteoclast stimulating factor 1; OSTF1, also named OSF or SH3P2, is a signaling protein containing SH3 and ankyrin-repeat domains. It acts through a Src-related pathway to enhance the formation of osteoclasts and bone resorption. It also acts as a negative regulator of cell motility. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212706 [Multi-domain] Cd Length: 53 Bit Score: 68.10 E-value: 4.06e-14

                           10        20        30        40
                   ....*....|....*....|....*....|....*....|....*...
gi 1804876928 1155 AMYDYVANNEDELNFSKGQLINVLNKDDPDWWQGEINGVTGLFPSNYV 1202
Cdd:cd11772      4 ALYDYEAQHPDELSFEEGDLLYISDKSDPNWWKATCGGKTGLIPSNYV 51

RecF/RecN/SMC N terminal domain; This domain is found at the N terminus of SMC proteins. The SMC (structural maintenance of chromosomes) superfamily proteins have ATP-binding domains at the N- and C-termini, and two extended coiled-coil domains separated by a hinge in the middle. The eukaryotic SMC proteins form two kind of heterodimers: the SMC1/SMC3 and the SMC2/SMC4 types. These heterodimers constitute an essential part of higher order complexes, which are involved in chromatin and DNA dynamics. This family also includes the RecF and RecN proteins that are involved in DNA metabolism and recombination.

Pssm-ID: 426784 [Multi-domain] Cd Length: 1161 Bit Score: 78.09 E-value: 4.42e-14

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1804876928  384 QKIQEEEPQKKLPVTFEDKRKANYErgNVELEKRRQALMEQqqreaERKAQKEKEEWERKQRELQEQEWKKQLELEKRLE 463
Cdd:pfam02463  167 LKRKKKEALKKLIEETENLAELIID--LEELKLQELKLKEQ-----AKKALEYYQLKEKLELEEEYLLYLDYLKLNEERI 239

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1804876928  464 KQRELERQREEERRKEIERREAAKQELERQrrlewerirrqellNQRNREQEEIVRLNSKKKSLHLELEALNGKHQQISG 543
Cdd:pfam02463  240 DLLQELLRDEQEEIESSKQEIEKEEEKLAQ--------------VLKENKEEEKEKKLQEEELKLLAKEEEELKSELLKL 305

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1804876928  544 RLQDVRLRKQTQ--KTEIEVLDKQCDLEIMEIKQLQQELQDYQNKliylvpeKQLLNERIKNMqlgntpdlgidllhkkS 621
Cdd:pfam02463  306 ERRKVDDEEKLKesEKEKKKAEKELKKEKEEIEELEKELKELEIK-------REAEEEEEEEL----------------E 362

                          250       260       270       280       290       300       310       320
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1804876928  622 LEKEELCQRLKEQLDALEKETASKLSEMDSFNNQLKCGNMDDSVLQcllsllsclnnlflLLKELREsynTQQLALEQLH 701
Cdd:pfam02463  363 KLQEKLEQLEEELLAKKKLESERLSSAAKLKEEELELKSEEEKEAQ--------------LLLELAR---QLEDLLKEEK 425

                          330       340       350       360       370       380       390
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|...
gi 1804876928  702 KIKRDKLKEIErKRSELIQKKKLEDEAIRKAKQGKENLWRESLRKEEEEKQKRLQEEKTQEKVQEEERKVEEK 774
Cdd:pfam02463  426 KEELEILEEEE-ESIELKQGKLTEEKEELEKQELKLLKDELELKKSEDLLKETQLVKLQEQLELLLSRQKLEE 497

C-terminal Src homology 3 domain of Growth factor receptor-bound protein 2; GRB2 is a critical signaling molecule that regulates the Ras pathway by linking tyrosine kinases to the Ras guanine nucleotide releasing protein Sos (son of sevenless), which converts Ras to the active GTP-bound state. It is ubiquitously expressed in all tissues throughout development and is important in cell cycle progression, motility, morphogenesis, and angiogenesis. In lymphocytes, GRB2 is associated with antigen receptor signaling components. GRB2 contains an N-terminal SH3 domain, a central SH2 domain, and a C-terminal SH3 domain. The C-terminal SH3 domain of GRB2 binds to Gab2 (Grb2-associated binder 2) through epitopes containing RxxK motifs, as well as to the proline-rich C-terminus of FGRF2. SH3 domains are protein interaction domains that typically bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212882 [Multi-domain] Cd Length: 53 Bit Score: 67.94 E-value: 4.92e-14

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|.
gi 1804876928 1153 VIAMYDYVANNEDELNFSKGQLINVLNKDDPDWWQGEINGVTGLFPSNYVK 1203
Cdd:cd11949      2 VQALFDFDPQEDGELGFRRGDFIEVMDNSDPNWWKGACHGQTGMFPRNYVT 52

Src Homology 3 domain of Pak Interactive eXchange factors; PIX proteins are Rho guanine nucleotide exchange factors (GEFs), which activate small GTPases by exchanging bound GDP for free GTP. They act as GEFs for both Cdc42 and Rac 1, and have been implicated in cell motility, adhesion, neurite outgrowth, and cell polarity. Vertebrates contain two proteins from the PIX subfamily, alpha-PIX and beta-PIX. Alpha-PIX, also called ARHGEF6, is localized in dendritic spines where it regulates spine morphogenesis. Mutations in the ARHGEF6 gene cause X-linked intellectual disability in humans. Beta-PIX play roles in regulating neuroendocrine exocytosis, focal adhesion maturation, cell migration, synaptic vesicle localization, and insulin secretion. PIX proteins contain an N-terminal SH3 domain followed by RhoGEF (also called Dbl-homologous or DH) and Pleckstrin Homology (PH) domains, and a C-terminal leucine-zipper domain for dimerization. The SH3 domain of PIX binds to an atypical PxxxPR motif in p21-activated kinases (PAKs) with high affinity. The binding of PAKs to PIX facilitate the localization of PAKs to focal complexes and also localizes PAKs to PIX targets Cdc43 and Rac, leading to the activation of PAKs. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212810 [Multi-domain] Cd Length: 53 Bit Score: 67.72 E-value: 6.36e-14

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|...
gi 1804876928  785 YKALYRFEARSHDEMSFNSGDIIQVDEKTIGepGWLYGSFQGNFGWFPCNYVE 837
Cdd:cd11877      2 VRAKFNFEGTNEDELSFDKGDIITVTQVVEG--GWWEGTLNGKTGWFPSNYVK 52

Cytoskeletal-regulatory complex EF hand; This is an efhand family from the N-terminal of actin cytoskeleton-regulatory complex END3 and similar proteins from fungi and closely related species.

Pssm-ID: 289529 Cd Length: 104 Bit Score: 69.32 E-value: 6.67e-14

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....*..
gi 1804876928   64 FDSLKPSGGYITGDQARTFFLQSGLPAPVLAEIWALSDLNKDGKMDQQEFSIAMKLI 120
Cdd:pfam12763   16 FSGLKPENNKLTGDQVSPVLKNSRLPDDQLAKIWDLADIDSDGKLDFEEFCIAMRLI 72

Src Homology 3 domain superfamily; Src Homology 3 (SH3) domains are protein interaction domains that bind proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. Thus, they are referred to as proline-recognition domains (PRDs). SH3 domains are less selective and show more diverse specificity compared to other PRDs. They have been shown to bind peptide sequences that lack the PxxP motif; examples include the PxxDY motif of Eps8 and the RKxxYxxY sequence in SKAP55. SH3 domain containing proteins play versatile and diverse roles in the cell, including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies, among others. Many members of this superfamily are adaptor proteins that associate with a number of protein partners, facilitating complex formation and signal transduction.

Pssm-ID: 212690 [Multi-domain] Cd Length: 51 Bit Score: 67.10 E-value: 8.09e-14

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|
gi 1804876928 1007 YIALYSYSSVEPGDLTFIEGEEILVTQK-DGEWWTGSIGD-RTGIFPSNY 1054
Cdd:cd00174      2 ARALYDYEAQDDDELSFKKGDIITVLEKdDDGWWEGELNGgREGLFPANY 51

C-terminal Src homology 3 domain of Growth factor receptor-bound protein 2 (GRB2) and related proteins; This family includes the adaptor protein GRB2 and related proteins including Drosophila melanogaster Downstream of receptor kinase (DRK), Caenorhabditis elegans Sex muscle abnormal protein 5 (Sem-5), GRB2-related adaptor protein (GRAP), GRAP2, and similar proteins. Family members contain an N-terminal SH3 domain, a central SH2 domain, and a C-terminal SH3 domain. GRB2/Sem-5/DRK is a critical signaling molecule that regulates the Ras pathway by linking tyrosine kinases to the Ras guanine nucleotide releasing protein Sos (son of sevenless), which converts Ras to the active GTP-bound state. GRAP2 plays an important role in T cell receptor (TCR) signaling by promoting the formation of the SLP-76:LAT complex, which couples the TCR to the Ras pathway. GRAP acts as a negative regulator of T cell receptor (TCR)-induced lymphocyte proliferation by downregulating the signaling to the Ras/ERK pathway. The C-terminal SH3 domains (SH3c) of GRB2 and GRAP2 have been shown to bind to classical PxxP motif ligands, as well as to non-classical motifs. GRB2 SH3c binds Gab2 (Grb2-associated binder 2) through epitopes containing RxxK motifs, while the SH3c of GRAP2 binds to the phosphatase-like protein HD-PTP via a RxxxxK motif. SH3 domains are protein interaction domains that typically bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212739 [Multi-domain] Cd Length: 53 Bit Score: 67.27 E-value: 9.59e-14

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|
gi 1804876928 1009 ALYSYSSVEPGDLTFIEGEEILVTQK-DGEWWTGSIGDRTGIFPSNYVKP 1057
Cdd:cd11805      4 ALYDFNPQEPGELEFRRGDIITVLDSsDPDWWKGELRGRVGIFPANYVQP 53

Third Src Homology 3 domain (SH3C) of Cbl-interacting protein of 85 kDa; CIN85, also called SH3 domain-containing kinase-binding protein 1 (SH3KBP1) or CD2-binding protein 3 (CD2BP3) or Ruk, is an adaptor protein that is involved in the downregulation of receptor tyrosine kinases by facilitating endocytosis through interaction with endophilin-associated ubiquitin ligase Cbl proteins. It is also important in many other cellular processes including vesicle-mediated transport, cytoskeletal remodelling, apoptosis, cell adhesion and migration, and viral infection, among others. CIN85 exists as multiple variants from alternative splicing; the main variant contains three SH3 domains, a proline-rich region, and a C-terminal coiled-coil domain. All of these domains enable CIN85 to bind various protein partners and assemble complexes that have been implicated in many different functions. This alignment model represents the third SH3 domain (SH3C) of CIN85. SH3C has been shown to bind ubiquitin. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212990 [Multi-domain] Cd Length: 56 Bit Score: 67.23 E-value: 1.01e-13

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....*.
gi 1804876928 1151 CQVIamYDYVANNEDELNFSKGQLINVLNKD--DPDWWQGEINGVTGLFPSNYVKM 1204
Cdd:cd12057      2 CKVL--FPYEAQNEDELTIKEGDIVTLISKDciDAGWWEGELNGRRGVFPDNFVKL 55

Src homology 3 domain of Abl Interactor 1; Abi1, also called e3B1, is a central regulator of actin cytoskeletal reorganization through interactions with many protein complexes. It is part of WAVE, a nucleation-promoting factor complex, that links Rac 1 activation to actin polymerization causing lamellipodia protrusion at the plasma membrane. Abi1 interact with formins to promote protrusions at the leading edge of motile cells. It also is a target of alpha4 integrin, regulating membrane protrusions at sites of integrin engagement. Abi proteins are adaptor proteins serving as binding partners and substrates of Abl tyrosine kinases. They are involved in regulating actin cytoskeletal reorganization and play important roles in membrane-ruffling, endocytosis, cell motility, and cell migration. Abi proteins contain a homeobox homology domain, a proline-rich region, and a SH3 domain. The SH3 domain of Abi binds to a PxxP motif in Abl. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212904 [Multi-domain] Cd Length: 59 Bit Score: 67.35 E-value: 1.01e-13

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|..
gi 1804876928 1152 QVIAMYDYVANNEDELNFSKGQLINVLNKDDPDWWQGEINGVTGLFPSNYVK 1203
Cdd:cd11971      1 KVVAIYDYSKDKDDELSFMEGAIIYVIKKNDDGWYEGVCNGVTGLFPGNYVE 52

Src homology 3 domain of Myosins Ie, If, and similar proteins; Myosins Ie (MyoIe) and If (MyoIf) are nonmuscle, unconventional, long tailed, class I myosins containing an N-terminal motor domain and a myosin tail with TH1, TH2, and SH3 domains. MyoIe interacts with the endocytic proteins, dynamin and synaptojanin-1, through its SH3 domain; it may play a role in clathrin-dependent endocytosis. In the kidney, MyoIe is critical for podocyte function and normal glomerular filtration. Mutations in MyoIe is associated with focal segmental glomerulosclerosis, a disease characterized by massive proteinuria and progression to end-stage kidney disease. MyoIf is predominantly expressed in the immune system; it plays a role in immune cell motility and innate immunity. Mutations in MyoIf may be associated with the loss of hearing. The MyoIf gene has also been found to be fused to the MLL (Mixed lineage leukemia) gene in infant acute myeloid leukemias (AML). SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212761 [Multi-domain] Cd Length: 53 Bit Score: 67.05 E-value: 1.13e-13

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|.
gi 1804876928 1152 QVIAMYDYVANNEDELNFSKGQLINVLNKDDPDWWQGEINGVTGLFPSNYV 1202
Cdd:cd11827      1 QCKALYAYDAQDTDELSFNEGDIIEILKEDPSGWWTGRLRGKEGLFPGNYV 51

Src homology 3 domain of Endophilin-A; Endophilins play roles in synaptic vesicle formation, virus budding, mitochondrial morphology maintenance, receptor-mediated endocytosis inhibition, and endosomal sorting. They are classified into two types, A and B. Vertebrates contain three endophilin-A isoforms (A1, A2, and A3). Endophilin-A proteins are enriched in the brain and play multiple roles in receptor-mediated endocytosis. They tubulate membranes and regulate calcium influx into neurons to trigger the activation of the endocytic machinery. They are also involved in the sorting of plasma membrane proteins, actin filament assembly, and the uncoating of clathrin-coated vesicles for fusion with endosomes. Endophilins contain an N-terminal N-BAR domain (BAR domain with an additional N-terminal amphipathic helix), followed by a variable region containing proline clusters, and a C-terminal SH3 domain. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212737 [Multi-domain] Cd Length: 55 Bit Score: 66.90 E-value: 1.23e-13

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....
gi 1804876928 1149 PVCQviAMYDYVANNEDELNFSKGQLINVLNKDDPDWWQGEINGVTGLFPSNYV 1202
Cdd:cd11803      1 PCCR--ALYDFEPENEGELGFKEGDIITLTNQIDENWYEGMVNGQSGFFPVNYV 52

MAEBL; Provisional

Pssm-ID: 173412 [Multi-domain] Cd Length: 2084 Bit Score: 76.33 E-value: 1.60e-13

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1804876928  385 KIQEEEPQKK---LPVTFEDKRKAnyERGNVELEKRRQALMEQQQREAERKAQ--KEKEEWERKQRELQE--QEWKKQLE 457
Cdd:PTZ00121  1397 KKKAEEDKKKadeLKKAAAAKKKA--DEAKKKAEEKKKADEAKKKAEEAKKADeaKKKAEEAKKAEEAKKkaEEAKKADE 1474

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1804876928  458 LEKRLEKQRELERQREEERRKEIERREAAKQELERQRRlewERIRRQEllnqRNREQEEIVRLNSKKKSLHLELEALNGK 537
Cdd:PTZ00121  1475 AKKKAEEAKKADEAKKKAEEAKKKADEAKKAAEAKKKA---DEAKKAE----EAKKADEAKKAEEAKKADEAKKAEEKKK 1547

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1804876928  538 HQQISgrlQDVRLRKQTQKTEIEVLDKQCDLEIMEIKQlQQELQDYQNKLIYLVPEKQLLNERIKNMQLGNTPDLGIDll 617
Cdd:PTZ00121  1548 ADELK---KAEELKKAEEKKKAEEAKKAEEDKNMALRK-AEEAKKAEEARIEEVMKLYEEEKKMKAEEAKKAEEAKIK-- 1621

                          250       260       270       280       290       300       310       320
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1804876928  618 hKKSLEKEELCQRLKEQLDALEKETASKLSEMDSFNNQLKCGNMDDSVLQCLLSLLSclnnlflllKELRESYNTQQLAL 697
Cdd:PTZ00121  1622 -AEELKKAEEEKKKVEQLKKKEAEEKKKAEELKKAEEENKIKAAEEAKKAEEDKKKA---------EEAKKAEEDEKKAA 1691

                          330       340       350       360       370       380       390       400
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1804876928  698 EQLHKIKRDKLK--EIERKRSELIQK----KKLEDEAIRKAKQGK-----ENLWRESLRKEEEEKQKRLQEEKTQEKVQE 766
Cdd:PTZ00121  1692 EALKKEAEEAKKaeELKKKEAEEKKKaeelKKAEEENKIKAEEAKkeaeeDKKKAEEAKKDEEEKKKIAHLKKEEEKKAE 1771

                          410       420       430       440
                   ....*....|....*....|....*....|....*....|....*.
gi 1804876928  767 EERKVEEKQCEPASALVNYKALYRFEARSHDEMSfNSGDIIQVDEK 812
Cdd:PTZ00121  1772 EIRKEKEAVIEEELDEEDEKRRMEVDKKIKDIFD-NFANIIEGGKE 1816

Src Homology 3 domain superfamily; Src Homology 3 (SH3) domains are protein interaction domains that bind proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. Thus, they are referred to as proline-recognition domains (PRDs). SH3 domains are less selective and show more diverse specificity compared to other PRDs. They have been shown to bind peptide sequences that lack the PxxP motif; examples include the PxxDY motif of Eps8 and the RKxxYxxY sequence in SKAP55. SH3 domain containing proteins play versatile and diverse roles in the cell, including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies, among others. Many members of this superfamily are adaptor proteins that associate with a number of protein partners, facilitating complex formation and signal transduction.

Pssm-ID: 212690 [Multi-domain] Cd Length: 51 Bit Score: 66.33 E-value: 1.87e-13

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|.
gi 1804876928  923 KAQALCSWTAKKDNHLNFSKHDIITVLEQQ-ENWWFGEVHGGR-GWFPKSY 971
Cdd:cd00174      1 YARALYDYEAQDDDELSFKKGDIITVLEKDdDGWWEGELNGGReGLFPANY 51

Src homology 3 domain of Ysc84p and similar fungal proteins; This family is composed of the Saccharomyces cerevisiae proteins, Ysc84p (also called LAS17-binding protein 4, Lsb4p) and Lsb3p, and similar fungal proteins. They contain an N-terminal SYLF domain (also called DUF500) and a C-terminal SH3 domain. Ysc84p localizes to actin patches and plays an important in actin polymerization during endocytosis. The N-terminal domain of both Ysc84p and Lsb3p can bind and bundle actin filaments. A study of the yeast SH3 domain interactome predicts that the SH3 domains of Lsb3p and Lsb4p may function as molecular hubs for the assembly of endocytic complexes. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212776 [Multi-domain] Cd Length: 55 Bit Score: 66.29 E-value: 2.23e-13

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....
gi 1804876928 1152 QVIAMYDYVANNEDELNFSKGQLINVLNKDDP--DWWQGEINGVTGLFPSNYVK 1203
Cdd:cd11842      1 KAVALYDFAGEQPGDLAFQKGDIITILKKSDSqnDWWTGRIGGREGIFPANYVE 54

Src Homology 3 domain of beta-Pak Interactive eXchange factor; Beta-PIX, also called Rho guanine nucleotide exchange factor 7 (ARHGEF7) or Cool (Cloned out of Library)-1, activates small GTPases by exchanging bound GDP for free GTP. It acts as a GEF for both Cdc42 and Rac 1, and plays important roles in regulating neuroendocrine exocytosis, focal adhesion maturation, cell migration, synaptic vesicle localization, and insulin secretion. PIX proteins contain an N-terminal SH3 domain followed by RhoGEF (also called Dbl-homologous or DH) and Pleckstrin Homology (PH) domains, and a C-terminal leucine-zipper domain for dimerization. The SH3 domain of PIX binds to an atypical PxxxPR motif in p21-activated kinases (PAKs) with high affinity. The binding of PAKs to PIX facilitate the localization of PAKs to focal complexes and also localizes PAKs to PIX targets Cdc43 and Rac, leading to the activation of PAKs. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212994 [Multi-domain] Cd Length: 54 Bit Score: 66.25 E-value: 2.24e-13

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|.
gi 1804876928 1153 VIAMYDYVANNEDELNFSKGQLINVLNKDDPDWWQGEINGVTGLFPSNYVK 1203
Cdd:cd12061      2 VRAKFNFQQTNEDELSFSKGDVIHVTRVEEGGWWEGTHNGRTGWFPSNYVR 52

Second C-terminal Src homology 3 domain of Fungal Actin-binding protein 1; Abp1 is an adaptor protein that functions in receptor-mediated endocytosis and vesicle trafficking. It contains an N-terminal actin-binding module, the actin-depolymerizing factor (ADF) homology domain, a central proline-rich region, and a C-terminal SH3 domain (many yeast Abp1 proteins contain two C-terminal SH3 domains). Yeast Abp1 also contains two acidic domains that bind directly to the Arp2/3 complex, which is required to initiate actin polymerization. The SH3 domain of yeast Abp1 binds and localizes the kinases, Ark1p and Prk1p, which facilitate actin patch disassembly following vesicle internalization. It also mediates the localization to the actin patch of the synaptojanin-like protein, Sjl2p, which plays a key role in endocytosis. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212894 [Multi-domain] Cd Length: 53 Bit Score: 66.01 E-value: 2.67e-13

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|..
gi 1804876928 1153 VIAMYDYVANNEDELNFSKGQLINVLNKDDPDWWQGEINGVTGLFPSNYVKM 1204
Cdd:cd11961      2 AKALYDYDAAEDNELSFFENDKIINIEFVDDDWWLGECHGSRGLFPSNYVEL 53

First Src Homology 3 domain (SH3A) of CD2-associated protein and similar proteins; This subfamily is composed of the first SH3 domain (SH3A) of CD2AP, CIN85 (Cbl-interacting protein of 85 kDa), and similar domains. CD2AP and CIN85 are adaptor proteins that bind to protein partners and assemble complexes that have been implicated in T cell activation, kidney function, and apoptosis of neuronal cells. They also associate with endocytic proteins, actin cytoskeleton components, and other adaptor proteins involved in receptor tyrosine kinase (RTK) signaling. CD2AP and the main isoform of CIN85 contain three SH3 domains, a proline-rich region, and a C-terminal coiled-coil domain. All of these domains enable CD2AP and CIN85 to bind various protein partners and assemble complexes that have been implicated in many different functions. SH3A of both proteins bind to an atypical PXXXPR motif at the C-terminus of Cbl and the cytoplasmic domain of the cell adhesion protein CD2. CIN85 SH3A binds to internal proline-rich motifs within the proline-rich region; this intramolecular interaction serves as a regulatory mechanism to keep CIN85 in a closed conformation, preventing the recruitment of other proteins. CIN85 SH3A has also been shown to bind ubiquitin. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212806 [Multi-domain] Cd Length: 53 Bit Score: 65.37 E-value: 3.36e-13

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|.
gi 1804876928 1153 VIAMYDYVANNEDELNFSKGQLINVLNKDDPDWWQGEINGVTGLFPSNYVK 1203
Cdd:cd11873      2 VIVEFDYDAEEPDELTLKVGDIITNVKKMEEGWWEGTLNGKRGMFPDNFVK 52

Variant SH3 domain; SH3 (Src homology 3) domains are often indicative of a protein involved in signal transduction related to cytoskeletal organization. First described in the Src cytoplasmic tyrosine kinase. The structure is a partly opened beta barrel.

Pssm-ID: 429575 [Multi-domain] Cd Length: 54 Bit Score: 65.31 E-value: 3.58e-13

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....
gi 1804876928  923 KAQALCSWTAKKDNHLNFSKHDIITVLEQ-QENWWFGEVHGGRGWFPKSYVKII 975
Cdd:pfam07653    1 YGRVIFDYVGTDKNGLTLKKGDVVKVLGKdNDGWWEGETGGRVGLVPSTAVEEI 54

Src homology 3 domain of Cortactin and related proteins; This subfamily includes cortactin, Abp1 (actin-binding protein 1), hematopoietic lineage cell-specific protein 1 (HS1), and similar proteins. These proteins are involved in regulating actin dynamics through direct or indirect interaction with the Arp2/3 complex, which is required to initiate actin polymerization. They all contain at least one C-terminal SH3 domain. Cortactin and HS1 bind Arp2/3 and actin through an N-terminal region that contains an acidic domain and several copies of a repeat domain found in cortactin and HS1. Abp1 binds actin via an N-terminal actin-depolymerizing factor (ADF) homology domain. Yeast Abp1 binds Arp2/3 directly through two acidic domains. Mammalian Abp1 does not directly interact with Arp2/3; instead, it regulates actin dynamics indirectly by interacting with dynamin and WASP family proteins. The C-terminal region of these proteins acts as an adaptor or scaffold that can connect membrane trafficking and signaling proteins that bind the SH3 domain within the actin network. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212753 [Multi-domain] Cd Length: 54 Bit Score: 65.41 E-value: 3.86e-13

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|..
gi 1804876928 1154 IAMYDYVANNEDELNFSKGQLINVLNKDDPDWWQGEIN-GVTGLFPSNYVKM 1204
Cdd:cd11819      3 KALYDYQAAEDNEISFVEGDIITQIEQIDEGWWLGVNAkGQKGLFPANYVEL 54

Src homology 3 domain of Signal Transducing Adaptor Molecule 2; STAM2, also called EAST (Epidermal growth factor receptor-associated protein with SH3 and TAM domain) or Hbp (Hrs binding protein), is part of the endosomal sorting complex required for transport (ESCRT-0). It plays a role in sorting mono-ubiquinated endosomal cargo for trafficking to the lysosome for degradation. It is also involved in the regulation of exocytosis. STAMs were discovered as proteins that are highly phosphorylated following cytokine and growth factor stimulation. They function in cytokine signaling and surface receptor degradation, as well as regulate Golgi morphology. They associate with many proteins including Jak2 and Jak3 tyrosine kinases, Hrs, AMSH, and UBPY. STAM adaptor proteins contain VHS (Vps27, Hrs, STAM homology), ubiquitin interacting (UIM), and SH3 domains. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212896 [Multi-domain] Cd Length: 57 Bit Score: 65.43 E-value: 3.89e-13

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....*.
gi 1804876928 1152 QVIAMYDYVANNEDELNFSKGQLINVLNKDDPDWWQGEINGVTGLFPSNYVkmTTD 1207
Cdd:cd11963      3 KVRALYDFEAVEDNELTFKHGEIIIVLDDSDANWWKGENHRGVGLFPSNFV--TTD 56

Src homology 3 domain of SH3 domain containing Ysc84-like 1 (SH3YL1) protein; SH3YL1 localizes to the plasma membrane and is required for dorsal ruffle formation. It binds phosphoinositides (PIs) with high affinity through its N-terminal SYLF domain (also called DUF500). In addition, SH3YL1 contains a C-terminal SH3 domain which has been reported to bind to N-WASP, dynamin 2, and SHIP2 (a PI 5-phosphatase). SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212775 Cd Length: 54 Bit Score: 65.49 E-value: 4.15e-13

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|.
gi 1804876928 1009 ALYSYSSVEPGDLTFIEGEEILV---TQKDGEWWTGSIGDRTGIFPSNYVK 1056
Cdd:cd11841      4 ALYSFEGQQPCDLSFQAGDRITVltrTDSQFDWWEGRLRGRVGIFPANYVS 54

Src homology 3 domain of Src kinase-like Protein Tyrosine Kinases; Src subfamily members include Src, Lck, Hck, Blk, Lyn, Fgr, Fyn, Yrk, Yes, and Brk. Src (or c-Src) proteins are cytoplasmic (or non-receptor) PTKs which are anchored to the plasma membrane. They contain an N-terminal SH4 domain with a myristoylation site, followed by SH3 and SH2 domains, a tyr kinase domain, and a regulatory C-terminal region containing a conserved tyr. They are activated by autophosphorylation at the tyr kinase domain, but are negatively regulated by phosphorylation at the C-terminal tyr by Csk (C-terminal Src Kinase). However, Brk lacks the N-terminal myristoylation sites. Src proteins are involved in signaling pathways that regulate cytokine and growth factor responses, cytoskeleton dynamics, cell proliferation, survival, and differentiation. They were identified as the first proto-oncogene products, and they regulate cell adhesion, invasion, and motility in cancer cells, and tumor vasculature, contributing to cancer progression and metastasis. Src kinases are overexpressed in a variety of human cancers, making them attractive targets for therapy. They are also implicated in acute inflammatory responses and osteoclast function. Src, Fyn, Yes, and Yrk are widely expressed, while Blk, Lck, Hck, Fgr, Lyn, and Brk show a limited expression pattern. This subfamily also includes Drosophila Src42A, Src oncogene at 42A (also known as Dsrc41) which accumulates at sites of cell-cell or cell-matrix adhesion, and participates in Drosphila development and wound healing. It has been shown to promote tube elongation in the tracheal system, is essential for proper cell-cell matching during dorsal closure, and regulates cell-cell contacts in developing Drosophila eyes. The SH3 domain of Src kinases contributes to substrate recruitment by binding adaptor proteins/substrates, and regulation of kinase activity through an intramolecular interaction. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212779 [Multi-domain] Cd Length: 52 Bit Score: 64.91 E-value: 5.03e-13

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|..
gi 1804876928 1152 QVIAMYDYVANNEDELNFSKGQLINVLNKDDPDWWQGE--INGVTGLFPSNY 1201
Cdd:cd11845      1 IYVALYDYEARTDDDLSFKKGDRLQILDDSDGDWWLARhlSTGKEGYIPSNY 52

Second Src Homology 3 domain of FCH and double SH3 domains proteins; This group is composed of FCH and double SH3 domains protein 1 (FCHSD1) and FCHSD2. These proteins have a common domain structure consisting of an N-terminal F-BAR (FES-CIP4 Homology and Bin/Amphiphysin/Rvs), two SH3, and C-terminal proline-rich domains. They have only been characterized in silico and their functions remain unknown. This group also includes the insect protein, nervous wreck, which acts as a regulator of synaptic growth signaling. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212696 [Multi-domain] Cd Length: 57 Bit Score: 65.11 E-value: 5.08e-13

                           10        20        30        40
                   ....*....|....*....|....*....|....*....|....*....
gi 1804876928 1155 AMYDYVANNEDELNFSKGQLINVLNKDDPD----WWQGEINGVTGLFPS 1199
Cdd:cd11762      4 ALYDYEAQSDEELSFPEGAIIRILRKDDNGvddgWWEGEFNGRVGVFPS 52

Src Homology 3 domain of Mixed Lineage Kinases 1, 2, and 3; MLKs 1, 2, and 3 are Serine/Threonine Kinases (STKs), catalyzing the transfer of the gamma-phosphoryl group from ATP to S/T residues on protein substrates. MLKs act as mitogen-activated protein kinase kinase kinases (MAP3Ks, MKKKs, MAPKKKs), which phosphorylate and activate MAPK kinases (MAPKKs or MKKs or MAP2Ks), which in turn phosphorylate and activate MAPKs during signaling cascades that are important in mediating cellular responses to extracellular signals. MLKs play roles in immunity and inflammation, as well as in cell death, proliferation, and cell cycle regulation. Little is known about the specific function of MLK1, also called MAP3K9. It is capable of activating the c-Jun N-terminal kinase pathway. Mice lacking both MLK1 and MLK2 are viable, fertile, and have normal life spans. MLK2, also called MAP3K10, is abundant in brain, skeletal muscle, and testis. It functions upstream of the MAPK, c-Jun N-terminal kinase. It binds hippocalcin, a calcium-sensor protein that protects neurons against calcium-induced cell death. Both MLK2 and hippocalcin may be associated with the pathogenesis of Parkinson's disease. MLK3, also called MAP3K11, is highly expressed in breast cancer cells and its signaling through c-Jun N-terminal kinase has been implicated in the migration, invasion, and malignancy of cancer cells. It also functions as a negative regulator of Inhibitor of Nuclear Factor-KappaB Kinase (IKK) and thus, impacts inflammation and immunity. MLKs contain an SH3 domain, a catalytic kinase domain, a leucine zipper, a proline-rich region, and a CRIB domain that mediates binding to GTP-bound Cdc42 and Rac. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212992 [Multi-domain] Cd Length: 58 Bit Score: 64.79 E-value: 6.90e-13

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....*
gi 1804876928 1155 AMYDYVANNEDELNFSKGQLINVLNKD-----DPDWWQGEINGVTGLFPSNYVKM 1204
Cdd:cd12059      4 AVFDYEASAEDELTLRRGDRVEVLSKDsavsgDEGWWTGKINDRVGIFPSNYVTS 58

Chromosome segregation ATPase Smc [Cell cycle control, cell division, chromosome partitioning];

Pssm-ID: 440809 [Multi-domain] Cd Length: 983 Bit Score: 73.82 E-value: 7.58e-13

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1804876928  384 QKIQEEEpqkklpVTFEDKRKANYERGN--VELEKRRQALMEQQQREAERKAQ--KEKEEWERKQRELQEQ--EWKKQLE 457
Cdd:COG1196    274 LELEELE------LELEEAQAEEYELLAelARLEQDIARLEERRRELEERLEEleEELAELEEELEELEEEleELEEELE 347

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1804876928  458 ---------LEKRLEKQRELERQREEERRKEIERREAAKQELERQRRLEWERIRRQELLNQRNREQEEIVRLNSKKKSLH 528
Cdd:COG1196    348 eaeeeleeaEAELAEAEEALLEAEAELAEAEEELEELAEELLEALRAAAELAAQLEELEEAEEALLERLERLEEELEELE 427

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1804876928  529 LELEALNGKHQQISGRLQDVRLRKQTQKTEIEVLDKQCDLEIMEIKQLQQELQDYQNKLIYLVPEKQLLNERIKNMQL-- 606
Cdd:COG1196    428 EALAELEEEEEEEEEALEEAAEEEAELEEEEEALLELLAELLEEAALLEAALAELLEELAEAAARLLLLLEAEADYEGfl 507

                          250       260       270       280       290       300       310       320
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1804876928  607 -------------GNTPDLGIDLLHKKSLEK---------------------EELCQRLKEQLDA------LEKETASKL 646
Cdd:COG1196    508 egvkaalllaglrGLAGAVAVLIGVEAAYEAaleaalaaalqnivveddevaAAAIEYLKAAKAGratflpLDKIRARAA 587

                          330       340       350       360       370       380       390       400
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1804876928  647 SEMDSFNNQLKCGNMDDSVLQCLLSLLSCLNNLFLLLKEL----RESYNTQQLALEQLHKIKRDKLKEIERKRSELIQKK 722
Cdd:COG1196    588 LAAALARGAIGAAVDLVASDLREADARYYVLGDTLLGRTLvaarLEAALRRAVTLAGRLREVTLEGEGGSAGGSLTGGSR 667

                          410       420       430       440       450
                   ....*....|....*....|....*....|....*....|....*....|...
gi 1804876928  723 KLEDEAIRKAKQGKENLWRESLRKEEEEKQKRLQEEKTQEKVQEEERKVEEKQ 775
Cdd:COG1196    668 RELLAALLEAEAELEELAERLAEEELELEEALLAEEEEERELAEAEEERLEEE 720

Src homology 3 domain of Proline-Serine-Threonine Phosphatase-Interacting Protein 1; PSTPIP1, also called CD2 Binding Protein 1 (CD2BP1), is mainly expressed in hematopoietic cells. It is a binding partner of the cell surface receptor CD2 and PTP-PEST, a tyrosine phosphatase which functions in cell motility and Rac1 regulation. It also plays a role in the activation of the Wiskott-Aldrich syndrome protein (WASP), which couples actin rearrangement and T cell activation. Mutations in the gene encoding PSTPIP1 cause the autoinflammatory disorder known as PAPA (pyogenic sterile arthritis, pyoderma gangrenosum, and acne) syndrome. PSTPIP1 contains an N-terminal F-BAR domain, PEST motifs, and a C-terminal SH3 domain. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212758 [Multi-domain] Cd Length: 53 Bit Score: 64.32 E-value: 8.28e-13

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|
gi 1804876928 1154 IAMYDYVANNEDELNFSKGQLINVLNKDDPDWWQGEINGVTGLFPSNYVK 1203
Cdd:cd11824      3 SVLYDYTAQEDDELSISKGDVVAVIEKGEDGWWTVERNGQKGLVPGTYLE 52

Src Homology 3 domain of GTPase Regulator Associated with Focal adhesion kinase and similar proteins; This subfamily is composed of Rho GTPase activating proteins (GAPs) with similarity to GRAF. Members contain an N-terminal BAR domain, followed by a Pleckstrin homology (PH) domain, a Rho GAP domain, and a C-terminal SH3 domain. Although vertebrates harbor four Rho GAPs in the GRAF subfamily including GRAF, GRAF2, GRAF3, and Oligophrenin-1 (OPHN1), only three are included in this model. OPHN1 contains the BAR, PH and GAP domains, but not the C-terminal SH3 domain. GRAF and GRAF2 show GAP activity towards RhoA and Cdc42. GRAF influences Rho-mediated cytoskeletal rearrangements and binds focal adhesion kinase. GRAF2 regulates caspase-activated p21-activated protein kinase-2. The SH3 domain of GRAF and GRAF2 binds PKNbeta, a target of the small GTPase Rho. SH3 domains bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs; they play a role in the regulation of enzymes by intramolecular interactions, changing the subcellular localization of signal pathway components and mediate multiprotein complex assemblies.

Pssm-ID: 212815 [Multi-domain] Cd Length: 54 Bit Score: 64.24 E-value: 1.04e-12

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|...
gi 1804876928 1152 QVIAMYDYVANNEDELNFSKGQLI-NVLNKDDPDWWQGEINGVTGLFPSNYVK 1203
Cdd:cd11882      1 RARALYACKAEDESELSFEPGQIItNVQPSDEPGWLEGTLNGRTGLIPENYVE 53

First Src Homology 3 domain (SH3A) of Cbl-interacting protein of 85 kDa; CIN85, also called SH3 domain-containing kinase-binding protein 1 (SH3KBP1) or CD2-binding protein 3 (CD2BP3) or Ruk, is an adaptor protein that is involved in the downregulation of receptor tyrosine kinases by facilitating endocytosis through interaction with endophilin-associated ubiquitin ligase Cbl proteins. It is also important in many other cellular processes including vesicle-mediated transport, cytoskeletal remodelling, apoptosis, cell adhesion and migration, and viral infection, among others. CIN85 exists as multiple variants from alternative splicing; the main variant contains three SH3 domains, a proline-rich region, and a C-terminal coiled-coil domain. All of these domains enable CIN85 to bind various protein partners and assemble complexes that have been implicated in many different functions. This alignment model represents the first SH3 domain (SH3A) of CIN85; SH3A binds to internal proline-rich motifs within the proline-rich region. This intramolecular interaction serves as a regulatory mechanism to keep CIN85 in a closed conformation, preventing the recruitment of other proteins. SH3A has also been shown to bind ubiquitin and to an atypical PXXXPR motif at the C-terminus of Cbl and the cytoplasmic end of the cell adhesion protein CD2. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212985 [Multi-domain] Cd Length: 53 Bit Score: 64.15 E-value: 1.19e-12

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|..
gi 1804876928 1152 QVIAMYDYVANNEDELNFSKGQLINVLNKDDPDWWQGEINGVTGLFPSNYVK 1203
Cdd:cd12052      1 EAIVEFDYKAQHEDELTITVGDIITKIKKDDGGWWEGEIKGRRGLFPDNFVR 52

Src homology 3 domain of ArfGAP with SH3 domain, ankyrin repeat and PH domain containing proteins; ASAPs are Arf GTPase activating proteins (GAPs) and they function in regulating cell growth, migration, and invasion. They contain an N-terminal BAR domain, followed by a Pleckstrin homology (PH) domain, an Arf GAP domain, ankyrin (ANK) repeats, and a C-terminal SH3 domain. Vertebrates contain at least three members, ASAP1, ASAP2, and ASAP3, but some ASAP3 proteins do not seem to harbor a C-terminal SH3 domain. ASAP1 and ASAP2 show GTPase activating protein (GAP) activity towards Arf1 and Arf5. They do not show GAP activity towards Arf6, but are able to mediate Arf6 signaling by binding stably to GTP-Arf6. ASAP3 is an Arf6-specific GAP. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212755 [Multi-domain] Cd Length: 53 Bit Score: 63.87 E-value: 1.21e-12

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|..
gi 1804876928 1153 VIAMYDYVANNEDELNFSKGQLINVLNKDDPDWWQGEING---VTGLFPSNY 1201
Cdd:cd11821      2 VRALYDCQADNDDELTFSEGEIIVVTGEEDDEWWEGHIEGdpsRRGVFPVSF 53

Chromosome segregation ATPase Smc [Cell cycle control, cell division, chromosome partitioning];

Pssm-ID: 440809 [Multi-domain] Cd Length: 983 Bit Score: 73.05 E-value: 1.33e-12

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1804876928  413 ELEKRRQALMEQQQREAERKAQKEKEEWERKQRELQEQEwKKQLELEKRLEKQRELERQREEERRKEIERREAAKQELER 492
Cdd:COG1196    221 ELKELEAELLLLKLRELEAELEELEAELEELEAELEELE-AELAELEAELEELRLELEELELELEEAQAEEYELLAELAR 299

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1804876928  493 -QRRLEWERIRRQELLNQRNREQEEIVRLNSKKKSLHLELEALNGKHQQISGRLQDVRLRKQTQKTEIEVLDKQCDLEIM 571
Cdd:COG1196    300 lEQDIARLEERRRELEERLEELEEELAELEEELEELEEELEELEEELEEAEEELEEAEAELAEAEEALLEAEAELAEAEE 379

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1804876928  572 EIKQLQQELQDYQNKLiylvpekqllneriknmqlgntpdlgidllhkksLEKEELCQRLKEQLDALEKETASKLSEmds 651
Cdd:COG1196    380 ELEELAEELLEALRAA----------------------------------AELAAQLEELEEAEEALLERLERLEEE--- 422

                          250       260       270       280       290       300       310       320
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1804876928  652 fnnqlkcgnmddsvlqcllsllsclnnlfllLKELRESYNTQQLALEQLHKIKRDKLKEIERKRSELIQKKKLEDEAIRK 731
Cdd:COG1196    423 -------------------------------LEELEEALAELEEEEEEEEEALEEAAEEEAELEEEEEALLELLAELLEE 471

                          330       340       350       360       370
                   ....*....|....*....|....*....|....*....|....*....|..
gi 1804876928  732 AKQGKENLwRESLRKEEEEKQKRLQEEKTQEKVQEEERKVEEKQCEPASALV 783
Cdd:COG1196    472 AALLEAAL-AELLEELAEAAARLLLLLEAEADYEGFLEGVKAALLLAGLRGL 522

Src homology 3 domain of Cortactin; Cortactin was originally identified as a substrate of Src kinase. It is an actin regulatory protein that binds to the Arp2/3 complex and stabilizes branched actin filaments. It is involved in cellular processes that affect cell motility, adhesion, migration, endocytosis, and invasion. It is expressed ubiquitously except in hematopoietic cells, where the homolog hematopoietic lineage cell-specific 1 (HS1) is expressed instead. Cortactin contains an N-terminal acidic domain, several copies of a repeat domain found in cortactin and HS1, a proline-rich region, and a C-terminal SH3 domain. The N-terminal region interacts with the Arp2/3 complex and F-actin, and is crucial in regulating branched actin assembly. Cortactin also serves as a scaffold and provides a bridge to the actin cytoskeleton for membrane trafficking and signaling proteins that bind to its SH3 domain. Binding partners for the SH3 domain of cortactin include dynamin2, N-WASp, MIM, FGD1, among others. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212892 [Multi-domain] Cd Length: 53 Bit Score: 63.98 E-value: 1.36e-12

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|.
gi 1804876928 1154 IAMYDYVANNEDELNFSKGQLINVLNKDDPDWWQGEINGVTGLFPSNYVKM 1204
Cdd:cd11959      3 VALYDYQAADDDEISFDPDDIITNIEMIDEGWWRGVCRGKYGLFPANYVEL 53

Cytoskeletal-regulatory complex EF hand; This is an efhand family from the N-terminal of actin cytoskeleton-regulatory complex END3 and similar proteins from fungi and closely related species.

Pssm-ID: 289529 Cd Length: 104 Bit Score: 65.47 E-value: 1.37e-12

                           10        20        30        40        50        60
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 1804876928  283 KYRQKFNSLdKSMSGYLSGFQARNALLQSNLSQTQLATIWTLADIDGDGQLRAEEFILAMHLT-DM 347
Cdd:pfam12763   11 KYWEIFSGL-KPENNKLTGDQVSPVLKNSRLPDDQLAKIWDLADIDSDGKLDFEEFCIAMRLIfDL 75

Src homology 3 domain of Protein arginine N-methyltransferase 2; PRMT2, also called HRMT1L1, belongs to the arginine methyltransferase protein family. It functions as a coactivator to both estrogen receptor alpha (ER-alpha) and androgen receptor (AR), presumably through arginine methylation. The ER-alpha transcription factor is involved in cell proliferation, differentiation, morphogenesis, and apoptosis, and is also implicated in the development and progression of breast cancer. PRMT2 and its variants are upregulated in breast cancer cells and may be involved in modulating the ER-alpha signaling pathway during formation of breast cancer. PRMT2 also plays a role in regulating the function of E2F transcription factors, which are critical cell cycle regulators, by binding to the retinoblastoma gene product (RB). It contains an N-terminal SH3 domain and an AdoMet binding domain. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212740 [Multi-domain] Cd Length: 53 Bit Score: 63.56 E-value: 1.60e-12

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|
gi 1804876928 1153 VIAMYDYVANNEDELNFSKGQLINVLNKDDPDWWQGEINGVTGLFPSNYV 1202
Cdd:cd11806      2 YVAIADFVATDDSQLSFESGDKLLVLRKPSVDWWWAEHNGCCGYIPASHL 51

Src homology 3 domain of Phospholipase C (PLC) gamma; PLC catalyzes the hydrolysis of phosphatidylinositol (4,5)-bisphosphate [PtdIns(4,5)P2] to produce Ins(1,4,5)P3 and diacylglycerol (DAG) in response to various receptors. Ins(1,4,5)P3 initiates the calcium signaling cascade while DAG functions as an activator of PKC. PLCgamma catalyzes this reaction in tyrosine kinase-dependent signaling pathways. It is activated and recruited to its substrate at the membrane. Vertebrates contain two forms of PLCgamma, PLCgamma1, which is widely expressed, and PLCgamma2, which is primarily found in haematopoietic cells. PLCgamma contains a Pleckstrin homology (PH) domain followed by an elongation factor (EF) domain, two catalytic regions of PLC domains that flank two tandem SH2 domains, followed by a SH3 domain and C2 domain. The SH3 domain of PLCgamma1 directly interacts with dynamin-1 and can serve as a guanine nucleotide exchange factor (GEF). It also interacts with Cbl, inhibiting its phosphorylation and activity. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212759 [Multi-domain] Cd Length: 54 Bit Score: 63.51 E-value: 1.72e-12

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|..
gi 1804876928 1153 VIAMYDYVANNEDELNFSKGQLINVLNKDDPDWWQGEING-VTGLFPSNYVK 1203
Cdd:cd11825      2 VKALYDYRAQRPDELSFCKHAIITNVEKEDGGWWRGDYGGkKQKWFPANYVE 53

Src homology 3 domain of Nitric Oxide Synthase TRaffic INducer; Nostrin is expressed in endothelial and epithelial cells and is involved in the regulation, trafficking and targeting of endothelial NOS (eNOS). It facilitates the endocytosis of eNOS by coordinating the functions of dynamin and the Wiskott-Aldrich syndrome protein (WASP). Increased expression of Nostrin may be correlated to preeclampsia. Nostrin contains an N-terminal F-BAR domain and a C-terminal SH3 domain. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212757 [Multi-domain] Cd Length: 53 Bit Score: 63.52 E-value: 1.78e-12

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|..
gi 1804876928  786 KALYRFEARSHDEMSFNSGDIIQVDEKtiGEPGWLYGSFQGNFGWFPCNYVE 837
Cdd:cd11823      3 KALYSYTANREDELSLQPGDIIEVHEK--QDDGWWLGELNGKKGIFPATYVE 52

Src homology 3 domain of Slit-Robo GTPase Activating Protein 4; srGAP4, also called ARHGAP4, is highly expressed in hematopoietic cells and may play a role in lymphocyte differentiation. It is able to stimulate the GTPase activity of Rac1, Cdc42, and RhoA. In the nervous system, srGAP4 has been detected in differentiating neurites and may be involved in axon and dendritic growth. srGAPs are Rho GAPs that interact with Robo1, the transmembrane receptor of Slit proteins. Slit proteins are secreted proteins that control axon guidance and the migration of neurons and leukocytes. srGAPs contain an N-terminal F-BAR domain, a Rho GAP domain, and a C-terminal SH3 domain. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212889 [Multi-domain] Cd Length: 55 Bit Score: 63.32 E-value: 1.92e-12

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|...
gi 1804876928 1150 VCQVIAMYDYVANNEDELNFSKGQLINVLNKDDPDWWQGEINGVTGLFPSNYV 1202
Cdd:cd11956      1 EVEAVACFDYTGRTAQELSFKRGDVLLLHSKASSDWWRGEHNGMRGLIPHKYI 53

Src Homology 3 domain superfamily; Src Homology 3 (SH3) domains are protein interaction domains that bind proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. Thus, they are referred to as proline-recognition domains (PRDs). SH3 domains are less selective and show more diverse specificity compared to other PRDs. They have been shown to bind peptide sequences that lack the PxxP motif; examples include the PxxDY motif of Eps8 and the RKxxYxxY sequence in SKAP55. SH3 domain containing proteins play versatile and diverse roles in the cell, including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies, among others. Many members of this superfamily are adaptor proteins that associate with a number of protein partners, facilitating complex formation and signal transduction.

Pssm-ID: 212690 [Multi-domain] Cd Length: 51 Bit Score: 63.25 E-value: 1.95e-12

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|..
gi 1804876928  785 YKALYRFEARSHDEMSFNSGDIIQVDEKTigEPGWLYGSFQGN-FGWFPCNY 835
Cdd:cd00174      2 ARALYDYEAQDDDELSFKKGDIITVLEKD--DDGWWEGELNGGrEGLFPANY 51

Third Src homology 3 domain (or SH3C) of Intersectin; Intersectins (ITSNs) are adaptor proteins that function in exo- and endocytosis, actin cytoskeletal reorganization, and signal transduction. They are essential for initiating clathrin-coated pit formation. They bind to many proteins through their multidomain structure and facilitate the assembly of multimeric complexes. Vertebrates contain two ITSN proteins, ITSN1 and ITSN2, which exist in alternatively spliced short and long isoforms. The short isoforms contain two Eps15 homology domains (EH1 and EH2), a coiled-coil region and five SH3 domains (SH3A-E), while the long isoforms, in addition, contain RhoGEF (also called Dbl-homologous or DH), Pleckstrin homology (PH) and C2 domains. ITSN1 and ITSN2 are both widely expressed, with variations depending on tissue type and stage of development. The third SH3 domain (or SH3C) of ITSN1 has been shown to bind many proteins including dynamin1/2, CIN85, c-Cbl, SHIP2, Reps1, synaptojanin-1, and WNK, among others. The SH3C of ITSN2 has been shown to bind the K15 protein of Kaposi's sarcoma-associated herpesvirus. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212772 [Multi-domain] Cd Length: 52 Bit Score: 63.20 E-value: 2.06e-12

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|
gi 1804876928 1154 IAMYDYVANNEDELNFSKGQLINVlNKDDPDWWQGEINGVTGLFPSNYVK 1203
Cdd:cd11838      3 IALYPYESNEPGDLTFNAGDVILV-TKKDGEWWTGTIGDRTGIFPSNYVR 51

Variant SH3 domain;

Pssm-ID: 434066 [Multi-domain] Cd Length: 49 Bit Score: 63.02 E-value: 2.09e-12

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|.
gi 1804876928  787 ALYRFEARSHDEMSFNSGDIIQVDEKTigEPGWLYGSFQGNFGWFPCNYVE 837
Cdd:pfam14604    1 ALYPYEPKDDDELSLQRGDVITVIEES--EDGWWEGINTGRTGLVPANYVE 49

Src Homology 3 domain of metazoan osteoclast stimulating factor 1; OSTF1, also named OSF or SH3P2, is a signaling protein containing SH3 and ankyrin-repeat domains. It acts through a Src-related pathway to enhance the formation of osteoclasts and bone resorption. It also acts as a negative regulator of cell motility. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212706 [Multi-domain] Cd Length: 53 Bit Score: 63.09 E-value: 2.31e-12

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|..
gi 1804876928 1007 YIALYSYSSVEPGDLTFIEGEEILVT-QKDGEWWTGSIGDRTGIFPSNYVKP 1057
Cdd:cd11772      2 FRALYDYEAQHPDELSFEEGDLLYISdKSDPNWWKATCGGKTGLIPSNYVEE 53

Src Homology 3 domain of Mixed Lineage Kinases; MLKs are Serine/Threonine Kinases (STKs), catalyzing the transfer of the gamma-phosphoryl group from ATP to S/T residues on protein substrates. MLKs act as mitogen-activated protein kinase kinase kinases (MAP3Ks, MKKKs, MAPKKKs), which phosphorylate and activate MAPK kinases (MAPKKs or MKKs or MAP2Ks), which in turn phosphorylate and activate MAPKs during signaling cascades that are important in mediating cellular responses to extracellular signals. MLKs play roles in immunity and inflammation, as well as in cell death, proliferation, and cell cycle regulation. Mammals have four MLKs (MLK1-4), mostly conserved in vertebrates, which contain an SH3 domain, a catalytic kinase domain, a leucine zipper, a proline-rich region, and a CRIB domain that mediates binding to GTP-bound Cdc42 and Rac. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212809 [Multi-domain] Cd Length: 58 Bit Score: 63.30 E-value: 2.41e-12

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|...
gi 1804876928 1155 AMYDYVANNEDELNFSKGQLINVLNKD-----DPDWWQGEINGVTGLFPSNYV 1202
Cdd:cd11876      4 ALFDYDARGEDELTLRRGQPVEVLSKDaavsgDEGWWTGKIGDKVGIFPSNYV 56

Src Homology 3 domain of Sdc25/Cdc25 guanine nucleotide exchange factors; This subfamily is composed of the Saccharomyces cerevisiae guanine nucleotide exchange factors (GEFs) Sdc25 and Cdc25, and similar proteins. These GEFs regulate Ras by stimulating the GDP/GTP exchange on Ras. Cdc25 is involved in the Ras/PKA pathway that plays an important role in the regulation of metabolism, stress responses, and proliferation, depending on available nutrients and conditions. Proteins in this subfamily contain an N-terminal SH3 domain as well as REM (Ras exchanger motif) and RasGEF domains at the C-terminus. SH3 domains bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs; they play a role in the regulation of enzymes by intramolecular interactions, changing the subcellular localization of signal pathway components and mediate multiprotein complex assemblies.

Pssm-ID: 212816 Cd Length: 55 Bit Score: 62.68 E-value: 3.51e-12

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....
gi 1804876928 1153 VIAMYDYVANNEDELNFSKGQLINVLNKDDPDWWQGEING-----VTGLFPSNY 1201
Cdd:cd11883      2 VVALYDFTPKSKNQLSFKAGDIIYVLNKDPSGWWDGVIISssgkvKRGWFPSNY 55

chromosome segregation protein SMC, common bacterial type; SMC (structural maintenance of chromosomes) proteins bind DNA and act in organizing and segregating chromosomes for partition. SMC proteins are found in bacteria, archaea, and eukaryotes. This family represents the SMC protein of most bacteria. The smc gene is often associated with scpB (TIGR00281) and scpA genes, where scp stands for segregation and condensation protein. SMC was shown (in Caulobacter crescentus) to be induced early in S phase but present and bound to DNA throughout the cell cycle. [Cellular processes, Cell division, DNA metabolism, Chromosome-associated proteins]

Pssm-ID: 274008 [Multi-domain] Cd Length: 1179 Bit Score: 71.63 E-value: 3.88e-12

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1804876928  383 YQKIQEEEPQKKLPVTFEDKRKANYERGNVELEKRRqalMEQQQREAERKAQKEKEEWERKQRELQEQEwKKQLELEKRL 462
Cdd:TIGR02168  215 YKELKAELRELELALLVLRLEELREELEELQEELKE---AEEELEELTAELQELEEKLEELRLEVSELE-EEIEELQKEL 290

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1804876928  463 EkqrelerqreeerrkeieRREAAKQELERQRRLEWERIRR------------QELLNQRNREQEEIVRLNSKKKSLHLE 530
Cdd:TIGR02168  291 Y------------------ALANEISRLEQQKQILRERLANlerqleeleaqlEELESKLDELAEELAELEEKLEELKEE 352

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1804876928  531 LEALNGKHQQISGRLQDVRLRKQTQKTEIEVLDKqcdleimEIKQLQQELQDYQNKLIYLVPEKQLLNERIKNMQLGNTp 610
Cdd:TIGR02168  353 LESLEAELEELEAELEELESRLEELEEQLETLRS-------KVAQLELQIASLNNEIERLEARLERLEDRRERLQQEIE- 424

                          250       260       270       280
                   ....*....|....*....|....*....|....*....|....*..
gi 1804876928  611 dlgidlLHKKSLEKEELcQRLKEQLDALEKETASKLSEMDSFNNQLK 657
Cdd:TIGR02168  425 ------ELLKKLEEAEL-KELQAELEELEEELEELQEELERLEEALE 464

Src Homology 3 domain of Mixed Lineage Kinase 4; MLK4 is a Serine/Threonine Kinase (STK), catalyzing the transfer of the gamma-phosphoryl group from ATP to S/T residues on protein substrates. MLKs act as mitogen-activated protein kinase kinase kinases (MAP3Ks, MKKKs, MAPKKKs), which phosphorylate and activate MAPK kinases (MAPKKs or MKKs or MAP2Ks), which in turn phosphorylate and activate MAPKs during signaling cascades that are important in mediating cellular responses to extracellular signals. MLKs play roles in immunity and inflammation, as well as in cell death, proliferation, and cell cycle regulation. The specific function of MLK4 is yet to be determined. Mutations in the kinase domain of MLK4 have been detected in colorectal cancers. MLK4 contains an SH3 domain, a catalytic kinase domain, a leucine zipper, a proline-rich region, and a CRIB domain that mediates binding to GTP-bound Cdc42 and Rac. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212991 [Multi-domain] Cd Length: 58 Bit Score: 62.65 E-value: 3.91e-12

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|...
gi 1804876928 1155 AMYDYVANNEDELNFSKGQLINVLNKD-----DPDWWQGEINGVTGLFPSNYV 1202
Cdd:cd12058      4 ALYDYEASGEDELSLRRGDVVEVLSQDaavsgDDGWWAGKIRHRLGIFPANYV 56

chromosome segregation protein SMC, primarily archaeal type; SMC (structural maintenance of chromosomes) proteins bind DNA and act in organizing and segregating chromosomes for partition. SMC proteins are found in bacteria, archaea, and eukaryotes. It is found in a single copy and is homodimeric in prokaryotes, but six paralogs (excluded from this family) are found in eukarotes, where SMC proteins are heterodimeric. This family represents the SMC protein of archaea and a few bacteria (Aquifex, Synechocystis, etc); the SMC of other bacteria is described by TIGR02168. The N- and C-terminal domains of this protein are well conserved, but the central hinge region is skewed in composition and highly divergent. [Cellular processes, Cell division, DNA metabolism, Chromosome-associated proteins]

Pssm-ID: 274009 [Multi-domain] Cd Length: 1164 Bit Score: 71.64 E-value: 3.99e-12

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1804876928  371 KQIDSINGTLPSYQKIQEEEPQKKLPVTFEDKRKANYERGNVELE----KRRQALMEQQQREAERKAQKEKEEWERKQRE 446
Cdd:TIGR02169  258 EEISELEKRLEEIEQLLEELNKKIKDLGEEEQLRVKEKIGELEAEiaslERSIAEKERELEDAEERLAKLEAEIDKLLAE 337

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1804876928  447 LQE-----QEWKKQLE-LEKRLEKQRELERQREEERRKEIERREAAKQEL-ERQRRLEWERIRRQELLNQRNREQEEIVR 519
Cdd:TIGR02169  338 IEElereiEEERKRRDkLTEEYAELKEELEDLRAELEEVDKEFAETRDELkDYREKLEKLKREINELKRELDRLQEELQR 417

                          170       180       190       200       210       220
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 1804876928  520 LNSKKKSLHLELEALNGKHQQISGRLQDVRLRKQTQKTEIEVLDKQCDLEIMEIKQLQQELQDYQNKL 587
Cdd:TIGR02169  418 LSEELADLNAAIAGIEAKINELEEEKEDKALEIKKQEWKLEQLAADLSKYEQELYDLKEEYDRVEKEL 485

Third Src homology 3 domain (or SH3C) of Intersectin-1; Intersectin-1 (ITSN1) is an adaptor protein that functions in exo- and endocytosis, actin cytoskeletal reorganization, and signal transduction. It plays a role in clathrin-coated pit (CCP) formation. It binds to many proteins through its multidomain structure and facilitate the assembly of multimeric complexes. ITSN1 localizes in membranous organelles, CCPs, the Golgi complex, and may be involved in the cell membrane trafficking system. It exists in alternatively spliced short and long isoforms. The short isoform contains two Eps15 homology domains (EH1 and EH2), a coiled-coil region and five SH3 domains (SH3A-E), while the long isoform, in addition, contains RhoGEF (also called Dbl-homologous or DH), Pleckstrin homology (PH) and C2 domains. The third SH3 domain (or SH3C) of ITSN1 has been shown to bind many proteins including dynamin1/2, CIN85, c-Cbl, SHIP2, Reps1, synaptojanin-1, and WNK, among others. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212924 Cd Length: 52 Bit Score: 62.31 E-value: 4.15e-12

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|...
gi 1804876928 1152 QVIAMYDYVANNEDELNFSKGQLINVLNKDDpDWWQGEINGVTGLFPSNYVKM 1204
Cdd:cd11991      1 EYVAMYTYESNEQGDLTFQQGDVILVTKKDG-DWWTGTVGDKTGVFPSNYVRP 52

Third Src Homology 3 domain of Nck adaptor proteins; This group contains the third SH3 domain of Nck, the first SH3 domain of Caenorhabditis elegans Ced-2 (Cell death abnormality protein 2), and similar domains. Nck adaptor proteins regulate actin cytoskeleton dynamics by linking proline-rich effector molecules to protein tyrosine kinases and phosphorylated signaling intermediates. They contain three SH3 domains and a C-terminal SH2 domain. They function downstream of the PDGFbeta receptor and are involved in Rho GTPase signaling and actin dynamics. Vertebrates contain two Nck adaptor proteins: Nck1 (also called Nckalpha) and Nck2 (also called Nckbeta or Growth factor receptor-bound protein 4, Grb4), which show partly overlapping functions but also bind distinct targets. Their SH3 domains are involved in recruiting downstream effector molecules, such as the N-WASP/Arp2/3 complex, which when activated induces actin polymerization that results in the production of pedestals, or protrusions of the plasma membrane. The third SH3 domain of Nck appears to prefer ligands with a PxAPxR motif. SH3 domains are protein interaction domains that usually bind to proline-rich ligands with moderate affinity and selectivity, preferentially a PxxP motif. Ced-2 is a cell corpse engulfment protein that interacts with Ced-5 in a pathway that regulates the activation of Ced-10, a Rac small GTPase.

Pssm-ID: 212701 [Multi-domain] Cd Length: 56 Bit Score: 62.33 E-value: 4.96e-12

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....
gi 1804876928 1153 VIAMYDYVANNEDELNFSKGQLINVLNK--DDPDWWQGE-INGVTGLFPSNYVK 1203
Cdd:cd11767      2 VVALYPFTGENDEELSFEKGERLEIIEKpeDDPDWWKARnALGTTGLVPRNYVE 55

Third Src Homology 3 domain (SH3C) of CD2-associated protein; CD2AP, also called CMS (Cas ligand with Multiple SH3 domains) or METS1 (Mesenchyme-to-Epithelium Transition protein with SH3 domains), is a cytosolic adaptor protein that plays a role in regulating the cytoskeleton. It is critical in cell-to-cell union necessary for kidney function. It also stabilizes the contact between a T cell and antigen-presenting cells. It is primarily expressed in podocytes at the cytoplasmic face of the slit diaphragm and serves as a linker anchoring podocin and nephrin to the actin cytoskeleton. CD2AP contains three SH3 domains, a proline-rich region, and a C-terminal coiled-coil domain. All of these domains enable CD2AP to bind various protein partners and assemble complexes that have been implicated in many different functions. This alignment model represents the third SH3 domain (SH3C) of CD2AP. SH3C has been shown to bind ubiquitin. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212989 [Multi-domain] Cd Length: 57 Bit Score: 62.15 E-value: 5.59e-12

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|
gi 1804876928 1155 AMYDYVANNEDELNFSKGQLINVLNKD--DPDWWQGEINGVTGLFPSNYV 1202
Cdd:cd12056      6 ALFHYEGTNEDELDFKEGEIILIISKDtgEPGWWKGELNGKEGVFPDNFV 55

Src Homology 3 domain of alpha-Pak Interactive eXchange factor; Alpha-PIX, also called Rho guanine nucleotide exchange factor 6 (ARHGEF6) or Cool (Cloned out of Library)-2, activates small GTPases by exchanging bound GDP for free GTP. It acts as a GEF for both Cdc42 and Rac 1, and is localized in dendritic spines where it regulates spine morphogenesis. It controls dendritic length and spine density in the hippocampus. Mutations in the ARHGEF6 gene cause X-linked intellectual disability in humans. PIX proteins contain an N-terminal SH3 domain followed by RhoGEF (also called Dbl-homologous or DH) and Pleckstrin Homology (PH) domains, and a C-terminal leucine-zipper domain for dimerization. The SH3 domain of PIX binds to an atypical PxxxPR motif in p21-activated kinases (PAKs) with high affinity. The binding of PAKs to PIX facilitate the localization of PAKs to focal complexes and also localizes PAKs to PIX targets Cdc43 and Rac, leading to the activation of PAKs. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212993 Cd Length: 58 Bit Score: 62.33 E-value: 6.35e-12

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|.
gi 1804876928 1153 VIAMYDYVANNEDELNFSKGQLINVLNKDDPDWWQGEINGVTGLFPSNYVK 1203
Cdd:cd12060      4 VKARFNFKQTNEDELSVCKGDIIYVTRVEEGGWWEGTLNGKTGWFPSNYVR 54

chromosome segregation protein SMC, primarily archaeal type; SMC (structural maintenance of chromosomes) proteins bind DNA and act in organizing and segregating chromosomes for partition. SMC proteins are found in bacteria, archaea, and eukaryotes. It is found in a single copy and is homodimeric in prokaryotes, but six paralogs (excluded from this family) are found in eukarotes, where SMC proteins are heterodimeric. This family represents the SMC protein of archaea and a few bacteria (Aquifex, Synechocystis, etc); the SMC of other bacteria is described by TIGR02168. The N- and C-terminal domains of this protein are well conserved, but the central hinge region is skewed in composition and highly divergent. [Cellular processes, Cell division, DNA metabolism, Chromosome-associated proteins]

Pssm-ID: 274009 [Multi-domain] Cd Length: 1164 Bit Score: 70.87 E-value: 6.58e-12

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1804876928  408 ERGNVELEKRRQALMEQQQREAERKAQKEkEEWERKQRELQEQEWKKQlELEKRLEKQRELERQREeerrkeierreAAK 487
Cdd:TIGR02169  715 SRKIGEIEKEIEQLEQEEEKLKERLEELE-EDLSSLEQEIENVKSELK-ELEARIEELEEDLHKLE-----------EAL 781

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1804876928  488 QELERQ-RRLEWERIRRQ-ELLNQRNREQEEIVR-LNSKKKSLHLELEALNGKHQQISGRLQDVRLRKQTQKTEIEVLDK 564
Cdd:TIGR02169  782 NDLEARlSHSRIPEIQAElSKLEEEVSRIEARLReIEQKLNRLTLEKEYLEKEIQELQEQRIDLKEQIKSIEKEIENLNG 861

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1804876928  565 QCDLEIMEIKQLQQELQDYQNKLIYLVPEKQLLNERIKNMQLG-NTPDLGIDLLHKKSLEKEELCQRLKEQLDALEKETA 643
Cdd:TIGR02169  862 KKEELEEELEELEAALRDLESRLGDLKKERDELEAQLRELERKiEELEAQIEKKRKRLSELKAKLEALEEELSEIEDPKG 941


                   ....*
gi 1804876928  644 SKLSE 648
Cdd:TIGR02169  942 EDEEI 946

N-terminal Src homology 3 domain of Growth factor receptor-bound protein 2; GRB2 is a critical signaling molecule that regulates the Ras pathway by linking tyrosine kinases to the Ras guanine nucleotide releasing protein Sos (son of sevenless), which converts Ras to the active GTP-bound state. It is ubiquitously expressed in all tissues throughout development and is important in cell cycle progression, motility, morphogenesis, and angiogenesis. In lymphocytes, GRB2 is associated with antigen receptor signaling components. GRB2 contains an N-terminal SH3 domain, a central SH2 domain, and a C-terminal SH3 domain. Its N-terminal SH3 domain binds to Sos and Sos-derived proline-rich peptides. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212879 [Multi-domain] Cd Length: 56 Bit Score: 61.97 E-value: 7.28e-12

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....
gi 1804876928 1152 QVIAMYDYVANNEDELNFSKGQLINVLNKD-DPDWWQGEINGVTGLFPSNYVKM 1204
Cdd:cd11946      2 EAIAKYDFKATADDELSFKRGDILKVLNEEcDQNWYKAELNGKDGFIPKNYIEM 55

Third Src Homology 3 domain of Nck1 adaptor protein; Nck1 (also called Nckalpha) plays a crucial role in connecting signaling pathways of tyrosine kinase receptors and important effectors in actin dynamics and cytoskeletal remodeling. It binds and activates RasGAP, resulting in the downregulation of Ras. It is also involved in the signaling of endothilin-mediated inhibition of cell migration. Nck adaptor proteins regulate actin cytoskeleton dynamics by linking proline-rich effector molecules to protein tyrosine kinases and phosphorylated signaling intermediates. They contain three SH3 domains and a C-terminal SH2 domain. They function downstream of the PDGFbeta receptor and are involved in Rho GTPase signaling and actin dynamics. Vertebrates contain two Nck adaptor proteins: Nck1 (also called Nckalpha) and Nck2, which show partly overlapping functions but also bind distinct targets. The third SH3 domain of Nck appears to prefer ligands with a PxAPxR motif. SH3 domains are protein interaction domains that usually bind to proline-rich ligands with moderate affinity and selectivity, preferentially a PxxP motif. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212837 [Multi-domain] Cd Length: 57 Bit Score: 61.97 E-value: 7.75e-12

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|...
gi 1804876928 1153 VIAMYDYVANNEDELNFSKGQLINVLNK--DDPDWWQ-GEINGVTGLFPSNYV 1202
Cdd:cd11904      3 VQALYPFSSSNDEELNFEKGEVMDVIEKpeNDPEWWKcRKANGQVGLVPKNYV 55

Second Src Homology 3 domain (SH3B) of CD2-associated protein; CD2AP, also called CMS (Cas ligand with Multiple SH3 domains) or METS1 (Mesenchyme-to-Epithelium Transition protein with SH3 domains), is a cytosolic adaptor protein that plays a role in regulating the cytoskeleton. It is critical in cell-to-cell union necessary for kidney function. It also stabilizes the contact between a T cell and antigen-presenting cells. It is primarily expressed in podocytes at the cytoplasmic face of the slit diaphragm and serves as a linker anchoring podocin and nephrin to the actin cytoskeleton. CD2AP contains three SH3 domains, a proline-rich region, and a C-terminal coiled-coil domain. All of these domains enable CD2AP to bind various protein partners and assemble complexes that have been implicated in many different functions. This alignment model represents the second SH3 domain (SH3B) of CD2AP. SH3B binds to c-Cbl in a site (TPSSRPLR is the core binding motif) distinct from the c-Cbl/SH3A binding site. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212987 [Multi-domain] Cd Length: 55 Bit Score: 61.91 E-value: 7.83e-12

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|...
gi 1804876928 1151 CQViaMYDYVANNEDELNFSKGQLINVLNKDDPDWWQGEINGVTGLFPSNYVK 1203
Cdd:cd12054      3 CKV--LFEYVPQNEDELELKVGDIIDINEEVEEGWWSGTLNGKSGLFPSNFVK 53

MAEBL; Provisional

Pssm-ID: 173412 [Multi-domain] Cd Length: 2084 Bit Score: 70.94 E-value: 8.62e-12

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1804876928  385 KIQEEEPQKK---LPVTFEDKRKANYERGNVElEKRRQALMEQQQREAERKAQ--KEKEEWERKQRELQE--QEWKKQLE 457
Cdd:PTZ00121  1370 EKKKEEAKKKadaAKKKAEEKKKADEAKKKAE-EDKKKADELKKAAAAKKKADeaKKKAEEKKKADEAKKkaEEAKKADE 1448

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1804876928  458 LEKRLEKQRELERqreeerrkeierreaAKQELERQRRLEWERIRRQEllnQRNREQEEIVRLNSKKKSLHLELEALNGK 537
Cdd:PTZ00121  1449 AKKKAEEAKKAEE---------------AKKKAEEAKKADEAKKKAEE---AKKADEAKKKAEEAKKKADEAKKAAEAKK 1510

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1804876928  538 HQQISGRLQDVR----LRKQTQKTEIEVLDKQCDLEIMEIKQLQQELQDYQNKliYLVPEKQLLNERiKNMQLGNTpdlg 613
Cdd:PTZ00121  1511 KADEAKKAEEAKkadeAKKAEEAKKADEAKKAEEKKKADELKKAEELKKAEEK--KKAEEAKKAEED-KNMALRKA---- 1583

                          250       260       270       280       290       300       310       320
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1804876928  614 iDLLHKKSLEKEELCQRLKEQLDALEKETASKLSEMDSFNNQLKcgnMDDSVLQCLLSLLSCLNNLFLLLKELRESYNTQ 693
Cdd:PTZ00121  1584 -EEAKKAEEARIEEVMKLYEEEKKMKAEEAKKAEEAKIKAEELK---KAEEEKKKVEQLKKKEAEEKKKAEELKKAEEEN 1659

                          330       340       350       360       370       380       390       400
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1804876928  694 QLALEQLHKIKRDKLKEIERKRSELIQKKKLEDEAIRKAKQGKEnlwRESLRKEEEEKQKRLQEEKTQE-----KVQEEE 768
Cdd:PTZ00121  1660 KIKAAEEAKKAEEDKKKAEEAKKAEEDEKKAAEALKKEAEEAKK---AEELKKKEAEEKKKAEELKKAEeenkiKAEEAK 1736


                   ....*..
gi 1804876928  769 RKVEEKQ 775
Cdd:PTZ00121  1737 KEAEEDK 1743

Src homology 3 domains; Src homology 3 (SH3) domains bind to target proteins through sequences containing proline and hydrophobic amino acids. Pro-containing polypeptides may bind to SH3 domains in 2 different binding orientations.

Pssm-ID: 214620 [Multi-domain] Cd Length: 56 Bit Score: 61.40 E-value: 9.77e-12

                            10        20        30        40        50        60
                    ....*....|....*....|....*....|....*....|....*....|....*....|
gi 1804876928  1075 KPEIAQVTSAYVASGSEQLSLAPGQLILILKKNSSGWWQGELqargKKRQKGWFPASHVK 1134
Cdd:smart00326    1 EGPQVRALYDYTAQDPDELSFKKGDIITVLEKSDDGWWKGRL----GRGKEGLFPSNYVE 56

Second Src Homology 3 domain (SH3B) of Cbl-interacting protein of 85 kDa; CIN85, also called SH3 domain-containing kinase-binding protein 1 (SH3KBP1) or CD2-binding protein 3 (CD2BP3) or Ruk, is an adaptor protein that is involved in the downregulation of receptor tyrosine kinases by facilitating endocytosis through interaction with endophilin-associated ubiquitin ligase Cbl proteins. It is also important in many other cellular processes including vesicle-mediated transport, cytoskeletal remodelling, apoptosis, cell adhesion and migration, and viral infection, among others. CIN85 exists as multiple variants from alternative splicing; the main variant contains three SH3 domains, a proline-rich region, and a C-terminal coiled-coil domain. All of these domains enable CIN85 to bind various protein partners and assemble complexes that have been implicated in many different functions. This alignment model represents the second SH3 domain (SH3B) of CIN85. SH3B has been shown to bind Cbl proline-rich peptides and ubiquitin. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212988 [Multi-domain] Cd Length: 53 Bit Score: 61.17 E-value: 1.16e-11

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|...
gi 1804876928 1151 CQViaMYDYVANNEDELNFSKGQLINVLNKDDPDWWQGEINGVTGLFPSNYVK 1203
Cdd:cd12055      2 CQV--AFSYLPQNEDELELKVGDIIEVVGEVEEGWWEGVLNGKTGMFPSNFIK 52

RhoGEF, Guanine nucleotide exchange factor for Rho/Rac/Cdc42-like GTPases [Signal transduction mechanisms];

Pssm-ID: 227709 [Multi-domain] Cd Length: 1175 Bit Score: 70.31 E-value: 1.17e-11

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1804876928 1228 ERKRQGYIHELIRTEERYVDDLQLVVEVFQKRMVESGFLTEGE----MALIFVNWKELIMCNTKLLKALRVRKKTggeKM 1303
Cdd:COG5422    482 EIKRQEAIYEVIYTERDFVKDLEYLRDTWIKPLEESNIIPENArrnfIKHVFANINEIYAVNSKLLKALTNRQCL---SP 558

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1804876928 1304 PVQTIGDILAAELSHMQAYIRFCSCQLNGAALLQQKTDEDTEFKEF--LKKLASDPRCKGmpLSSFLLKPMQRITRYPLL 1381
Cdd:COG5422    559 IVNGIADIFLDYVPKFEPFIKYGASQPYAKYEFEREKSVNPNFARFdhEVERLDESRKLE--LDGYLTKPTTRLARYPLL 636

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1804876928 1382 IRSILENTLENHVDHSSLKLALERAEELCSQVNEGVREKENsdRLEWIQahvqcdgLAEQLIFNSLTNCLG----PRKLL 1457
Cdd:COG5422    637 LEEVLKFTDPDNPDTEDIPKVIDMLREFLSRLNFESGKAEN--RGDLFH-------LNQQLLFKPEYVNLGlndeYRKII 707

                          250       260       270
                   ....*....|....*....|....*....|..
gi 1804876928 1458 HSGKLYKTKSNK-------ELHGFLFNDFLLL 1482
Cdd:COG5422    708 FKGVLKRKAKSKtdgslrgDIQFFLLDNMLLF 739

Src Homology 3 domain of metazoan osteoclast stimulating factor 1; OSTF1, also named OSF or SH3P2, is a signaling protein containing SH3 and ankyrin-repeat domains. It acts through a Src-related pathway to enhance the formation of osteoclasts and bone resorption. It also acts as a negative regulator of cell motility. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212706 [Multi-domain] Cd Length: 53 Bit Score: 60.78 E-value: 1.47e-11

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|...
gi 1804876928  785 YKALYRFEARSHDEMSFNSGDIIQVDEKTigEPGWLYGSFQGNFGWFPCNYVE 837
Cdd:cd11772      2 FRALYDYEAQHPDELSFEEGDLLYISDKS--DPNWWKATCGGKTGLIPSNYVE 52

C-terminal (or second) Src Homology 3 domain of the p67phox subunit of NADPH oxidase; p67phox, also called Neutrophil cytosol factor 2 (NCF-2), is a cytosolic subunit of the phagocytic NADPH oxidase complex (also called Nox2 or gp91phox) which plays a crucial role in the cellular response to bacterial infection. NADPH oxidase catalyzes the transfer of electrons from NADPH to oxygen during phagocytosis forming superoxide and reactive oxygen species. p67phox plays a regulatory role and contains N-terminal TPR, first SH3 (or N-terminal or central SH3), PB1, and C-terminal SH3 domains. It binds, via its C-terminal SH3 domain, to a proline-rich region of p47phox and upon activation, this complex assembles with flavocytochrome b558, the Nox2-p22phox heterodimer. Concurrently, RacGTP translocates to the membrane and interacts with the TPR domain of p67phox, which leads to the activation of NADPH oxidase. The PB1 domain of p67phox binds to its partner PB1 domain in p40phox, and this facilitates the assembly of p47phox-p67phox at the membrane. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212979 [Multi-domain] Cd Length: 53 Bit Score: 60.97 E-value: 1.51e-11

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|..
gi 1804876928 1152 QVIAMYDYVANNEDELNFSKGQLINVLNKDDPDWWQGEINGVTGLFPSNYVK 1203
Cdd:cd12046      1 QVVALFSYEASQPEDLEFQKGDVILVLSKVNEDWLEGQCKGKIGIFPSAFVE 52

Src Homology 3 domain superfamily; Src Homology 3 (SH3) domains are protein interaction domains that bind proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. Thus, they are referred to as proline-recognition domains (PRDs). SH3 domains are less selective and show more diverse specificity compared to other PRDs. They have been shown to bind peptide sequences that lack the PxxP motif; examples include the PxxDY motif of Eps8 and the RKxxYxxY sequence in SKAP55. SH3 domain containing proteins play versatile and diverse roles in the cell, including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies, among others. Many members of this superfamily are adaptor proteins that associate with a number of protein partners, facilitating complex formation and signal transduction.

Pssm-ID: 212690 [Multi-domain] Cd Length: 51 Bit Score: 60.55 E-value: 1.59e-11

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....*
gi 1804876928 1078 IAQVTSAYVASGSEQLSLAPGQLILILKKNSSGWWQGELQargkKRQKGWFPASH 1132
Cdd:cd00174      1 YARALYDYEAQDDDELSFKKGDIITVLEKDDDGWWEGELN----GGREGLFPANY 51

Fifth Src homology 3 domain (or SH3E) of Intersectin; Intersectins (ITSNs) are adaptor proteins that function in exo- and endocytosis, actin cytoskeletal reorganization, and signal transduction. They are essential for initiating clathrin-coated pit formation. They bind to many proteins through their multidomain structure and facilitate the assembly of multimeric complexes. Vertebrates contain two ITSN proteins, ITSN1 and ITSN2, which exist in alternatively spliced short and long isoforms. The short isoforms contain two Eps15 homology domains (EH1 and EH2), a coiled-coil region and five SH3 domains (SH3A-E), while the long isoforms, in addition, contain RhoGEF (also called Dbl-homologous or DH), Pleckstrin homology (PH) and C2 domains. ITSN1 and ITSN2 are both widely expressed, with variations depending on tissue type and stage of development. The fifth SH3 domain (or SH3E) of ITSN1 has been shown to bind many protein partners including SGIP1, Sos1, dynamin1/2, CIN85, c-Cbl, SHIP2, N-WASP, and synaptojanin-1, among others. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212774 [Multi-domain] Cd Length: 53 Bit Score: 60.51 E-value: 1.94e-11

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|.
gi 1804876928 1008 IALYSYSSVEPGDLTFIEGEEILVTQKD-GEWWTGSIGDRTGIFPSNYVKP 1057
Cdd:cd11840      3 IALFPYTAQNEDELSFQKGDIINVLSKDdPDWWRGELNGQTGLFPSNYVEP 53

Second Src Homology 3 domain of Bzz1 and similar domains; Bzz1 (or Bzz1p) is a WASP/Las17-interacting protein involved in endocytosis and trafficking to the vacuole. It physically interacts with type I myosins and functions in the early steps of endocytosis. Together with other proteins, it induces membrane scission in yeast. Bzz1 contains an N-terminal F-BAR (FES-CIP4 Homology and Bin/Amphiphysin/Rvs), a central coiled-coil, and two C-terminal SH3 domains. This model represents the second C-terminal SH3 domain. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212712 [Multi-domain] Cd Length: 51 Bit Score: 60.59 E-value: 2.06e-11

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|
gi 1804876928 1153 VIAMYDYVANNEDELNFSKGQLINVLNKDDPD-WWQGEINGVTGLFPSNY 1201
Cdd:cd11778      2 VEALYDYEAQGDDEISIRVGDRIAVIRGDDGSgWTYGEINGVKGLFPTSY 51

Src Homology 3 domain of Sdc25/Cdc25 guanine nucleotide exchange factors; This subfamily is composed of the Saccharomyces cerevisiae guanine nucleotide exchange factors (GEFs) Sdc25 and Cdc25, and similar proteins. These GEFs regulate Ras by stimulating the GDP/GTP exchange on Ras. Cdc25 is involved in the Ras/PKA pathway that plays an important role in the regulation of metabolism, stress responses, and proliferation, depending on available nutrients and conditions. Proteins in this subfamily contain an N-terminal SH3 domain as well as REM (Ras exchanger motif) and RasGEF domains at the C-terminus. SH3 domains bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs; they play a role in the regulation of enzymes by intramolecular interactions, changing the subcellular localization of signal pathway components and mediate multiprotein complex assemblies.

Pssm-ID: 212816 Cd Length: 55 Bit Score: 60.37 E-value: 2.43e-11

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....*
gi 1804876928 1078 IAQVTSAYVASGSEQLSLAPGQLILILKKNSSGWWQGELQARGKKRQKGWFPASH 1132
Cdd:cd11883      1 VVVALYDFTPKSKNQLSFKAGDIIYVLNKDPSGWWDGVIISSSGKVKRGWFPSNY 55

Second Src homology 3 domain (or SH3B) of Intersectin; Intersectins (ITSNs) are adaptor proteins that function in exo- and endocytosis, actin cytoskeletal reorganization, and signal transduction. They are essential for initiating clathrin-coated pit formation. They bind to many proteins through their multidomain structure and facilitate the assembly of multimeric complexes. Vertebrates contain two ITSN proteins, ITSN1 and ITSN2, which exist in alternatively spliced short and long isoforms. The short isoforms contain two Eps15 homology domains (EH1 and EH2), a coiled-coil region and five SH3 domains (SH3A-E), while the long isoforms, in addition, contain RhoGEF (also called Dbl-homologous or DH), Pleckstrin homology (PH) and C2 domains. ITSN1 and ITSN2 are both widely expressed, with variations depending on tissue type and stage of development. The second SH3 domain (or SH3B) of ITSN1 has been shown to bind WNK and CdGAP. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212771 [Multi-domain] Cd Length: 53 Bit Score: 60.07 E-value: 3.00e-11

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....
gi 1804876928 1152 QVIAMYDYVANNEDELNFSKGQLINVLNKDDpDWWQGEINGVT-GLFPSNYVKM 1204
Cdd:cd11837      1 TATALYPWRAKKENHLSFAKGDIITVLEQQE-MWWFGELEGGEeGWFPKSYVKE 53

helix-rich Mycoplasma protein; Members of this family occur strictly within a subset of Mycoplasma species. Members average 750 amino acids in length, including signal peptide. Sequences are predicted (Jpred 3) to be almost entirely alpha-helical. These sequences show strong periodicity (consistent with long alpha helical structures) and low complexity rich in D,E,N,Q, and K. Genes encoding these proteins are often found in tandem. The function is unknown.

Pssm-ID: 275316 [Multi-domain] Cd Length: 745 Bit Score: 68.51 E-value: 3.13e-11

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1804876928  402 KRKANYERGNVELEKrrqalmeqQQREAERKAQKEKEEWERKQRELQEQEWKKQlELEKRLEKQRELERQREEERrkeie 481
Cdd:TIGR04523  349 KELTNSESENSEKQR--------ELEEKQNEIEKLKKENQSYKQEIKNLESQIN-DLESKIQNQEKLNQQKDEQI----- 414

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1804876928  482 rreaakQELERQRRLEWERIrrQELLNQRNREQEEIVRLNSKKKSLHLELEALNGKhqqisgrlqdvrlrKQTQKTEIEV 561
Cdd:TIGR04523  415 ------KKLQQEKELLEKEI--ERLKETIIKNNSEIKDLTNQDSVKELIIKNLDNT--------------RESLETQLKV 472

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1804876928  562 LDKQCDLEIMEIKQLQQELQDYQNKLIYLVPEKQLLNERIKNmqlgntpdlgidlLHKKSLEKEELCQRLKEQLDALEKE 641
Cdd:TIGR04523  473 LSRSINKIKQNLEQKQKELKSKEKELKKLNEEKKELEEKVKD-------------LTKKISSLKEKIEKLESEKKEKESK 539

                          250       260       270       280       290       300       310       320
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1804876928  642 TASKLSEMDSFNNQLKCGNMDDSVLQCLLSLLSclnnlfllLKELRESYNTQQLALEQLHKIKRDKLKEIERKRSELIQK 721
Cdd:TIGR04523  540 ISDLEDELNKDDFELKKENLEKEIDEKNKEIEE--------LKQTQKSLKKKQEEKQELIDQKEKEKKDLIKEIEEKEKK 611

                          330       340       350       360       370
                   ....*....|....*....|....*....|....*....|....*....|....
gi 1804876928  722 K-KLEDEaIRKAKQGKENLwrESLRKEEEEKQKRLQEEKTQekVQEEERKVEEK 774
Cdd:TIGR04523  612 IsSLEKE-LEKAKKENEKL--SSIIKNIKSKKNKLKQEVKQ--IKETIKEIRNK 660

Src Homology 3 domain of Bbc1 and similar domains; This subfamily is composed of Saccharomyces cerevisiae Bbc1p, also called Mti1p (Myosin tail region-interacting protein), and similar proteins. Bbc1p interacts with and regulates type I myosins in yeast, Myo3p and Myo5p, which are involved in actin cytoskeletal reorganization. It also binds and inhibits Las17, a WASp family protein that functions as an activator of the Arp2/3 complex. Bbc1p contains an N-terminal SH3 domain. SH3 domains bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs; they play a role in the regulation of enzymes by intramolecular interactions, changing the subcellular localization of signal pathway components and mediate multiprotein complex assemblies.

Pssm-ID: 212820 [Multi-domain] Cd Length: 60 Bit Score: 60.05 E-value: 3.56e-11

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....*
gi 1804876928 1153 VIAMYDYVANNEDELNFSKGQLINVLNKDDPDWWQGEI---NGVT--GLFPSNYV 1202
Cdd:cd11887      4 VKALYPYESDHEDDLNFDVGQLITVTEEEDADWYFGEYvdsNGNTkeGIFPKNFV 58

chromosome segregation protein SMC, common bacterial type; SMC (structural maintenance of chromosomes) proteins bind DNA and act in organizing and segregating chromosomes for partition. SMC proteins are found in bacteria, archaea, and eukaryotes. This family represents the SMC protein of most bacteria. The smc gene is often associated with scpB (TIGR00281) and scpA genes, where scp stands for segregation and condensation protein. SMC was shown (in Caulobacter crescentus) to be induced early in S phase but present and bound to DNA throughout the cell cycle. [Cellular processes, Cell division, DNA metabolism, Chromosome-associated proteins]

Pssm-ID: 274008 [Multi-domain] Cd Length: 1179 Bit Score: 68.54 E-value: 3.93e-11

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1804876928  413 ELEKRRQALMEQQQREAErkAQKEKEEWERKQRELQEQEWKKQLELEkRLEKQRElerqreeerrkeierreAAKQELER 492
Cdd:TIGR02168  678 EIEELEEKIEELEEKIAE--LEKALAELRKELEELEEELEQLRKELE-ELSRQIS-----------------ALRKDLAR 737

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1804876928  493 QRRleweriRRQELLNQRNREQEEIVRLNSKKKSLHLELEALNGKHQQISGRLQDVRLRKQTQKTEIEVLDKQCDLEIME 572
Cdd:TIGR02168  738 LEA------EVEQLEERIAQLSKELTELEAEIEELEERLEEAEEELAEAEAEIEELEAQIEQLKEELKALREALDELRAE 811

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1804876928  573 IKQLQQELQDYQNKLIYLVPEKQLLNERIKNM--QLGNTPDLGIDLlhKKSLEK-EELCQRLKEQLDALEKETASKLSEM 649
Cdd:TIGR02168  812 LTLLNEEAANLRERLESLERRIAATERRLEDLeeQIEELSEDIESL--AAEIEElEELIEELESELEALLNERASLEEAL 889

                          250       260       270       280       290       300       310       320
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1804876928  650 DSFNNQLkcGNMDDSVLQCLLSLLSCLNnlflLLKELRESYNTQQLALEQLhKIKRDKLKEIERKR----SELIQKKKLE 725
Cdd:TIGR02168  890 ALLRSEL--EELSEELRELESKRSELRR----ELEELREKLAQLELRLEGL-EVRIDNLQERLSEEysltLEEAEALENK 962

                          330       340       350       360       370
                   ....*....|....*....|....*....|....*....|....*....|....*....
gi 1804876928  726 DEA--------IRKAKQGKENLWRESLRKEEE--EKQKRLQEEKTQ-EKVQEEERKVEE 773
Cdd:TIGR02168  963 IEDdeeearrrLKRLENKIKELGPVNLAAIEEyeELKERYDFLTAQkEDLTEAKETLEE 1021

Src homology 3 domain of Slit-Robo GTPase Activating Proteins; Slit-Robo GTPase Activating Proteins (srGAPs) are Rho GAPs that interact with Robo1, the transmembrane receptor of Slit proteins. Slit proteins are secreted proteins that control axon guidance and the migration of neurons and leukocytes. Vertebrates contain three isoforms of srGAPs (srGAP1-3), all of which are expressed during embryonic and early development in the nervous system but with different localization and timing. A fourth member has also been reported (srGAP4, also called ARHGAP4). srGAPs contain an N-terminal F-BAR domain, a Rho GAP domain, and a C-terminal SH3 domain. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212743 [Multi-domain] Cd Length: 53 Bit Score: 59.72 E-value: 3.93e-11

                           10        20        30        40
                   ....*....|....*....|....*....|....*....|....*....
gi 1804876928 1154 IAMYDYVANNEDELNFSKGQLINVLNKDDPDWWQGEINGVTGLFPSNYV 1202
Cdd:cd11809      3 TAQFDYTGRSERELSFKKGDSLTLYRQVSDDWWRGQLNGQDGLVPHKYI 51

C-terminal Src Homology 3 domain of the Nebulin family of proteins; Nebulin family proteins contain multiple nebulin repeats, and may contain an N-terminal LIM domain and/or a C-terminal SH3 domain. They have molecular weights ranging from 34 to 900 kD, depending on the number of nebulin repeats, and they all bind actin. They are involved in the regulation of actin filament architecture and function as stabilizers and scaffolds for cytoskeletal structures with which they associate, such as long actin filaments or focal adhesions. Nebulin family proteins that contain a C-terminal SH3 domain include the giant filamentous protein nebulin, nebulette, Lasp1, and Lasp2. Lasp2, also called LIM-nebulette, is an alternatively spliced variant of nebulette. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212723 [Multi-domain] Cd Length: 55 Bit Score: 59.64 E-value: 4.56e-11

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....*.
gi 1804876928  785 YKALYRFEARSHDEMSFNSGDIIqVDEKTIGEpGWLYGSFQ--GNFGWFPCNYVEK 838
Cdd:cd11789      2 YRAMYDYAAADDDEVSFQEGDVI-INVEIIDD-GWMEGTVQrtGQSGMLPANYVEL 55

Fourth Src homology 3 domain of ADAM-binding protein Eve-1; Eve-1, also called SH3 domain-containing protein 19 (SH3D19) or EEN-binding protein (EBP), exists in multiple alternatively spliced isoforms. The longest isoform contains five SH3 domain in the C-terminal region and seven proline-rich motifs in the N-terminal region. It is abundantly expressed in skeletal muscle and heart, and may be involved in regulating the activity of ADAMs (A disintegrin and metalloproteases). Eve-1 interacts with EEN, an endophilin involved in endocytosis and may be the target of the MLL-EEN fusion protein that is implicated in leukemogenesis. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212751 [Multi-domain] Cd Length: 50 Bit Score: 59.41 E-value: 4.91e-11

                           10        20        30        40
                   ....*....|....*....|....*....|....*....|....*....
gi 1804876928 1153 VIAMYDYVANNEDELNFSKGQLINVLNKDDPDWWQGEINGVTGLFPSNY 1201
Cdd:cd11817      2 AVALYDFTGETEEDLSFQRGDRILVTEHLDAEWSRGRLNGREGIFPRAF 50

RecF/RecN/SMC N terminal domain; This domain is found at the N terminus of SMC proteins. The SMC (structural maintenance of chromosomes) superfamily proteins have ATP-binding domains at the N- and C-termini, and two extended coiled-coil domains separated by a hinge in the middle. The eukaryotic SMC proteins form two kind of heterodimers: the SMC1/SMC3 and the SMC2/SMC4 types. These heterodimers constitute an essential part of higher order complexes, which are involved in chromatin and DNA dynamics. This family also includes the RecF and RecN proteins that are involved in DNA metabolism and recombination.

Pssm-ID: 426784 [Multi-domain] Cd Length: 1161 Bit Score: 68.07 E-value: 4.96e-11

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1804876928  417 RRQALMEQQQREAERKAQKEKEEWERKQREL----QEQEWKKQLELEKRLEKQRELERQREeerrkeierreaAKQELER 492
Cdd:pfam02463  145 EIIAMMKPERRLEIEEEAAGSRLKRKKKEALkkliEETENLAELIIDLEELKLQELKLKEQ------------AKKALEY 212

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1804876928  493 QRRLEWERIRRQELL--NQRNREQEEIVRLNskkkslhlELEALNGKHQQISGRLQDVRLRKQTQKTEIEVLDKQCD-LE 569
Cdd:pfam02463  213 YQLKEKLELEEEYLLylDYLKLNEERIDLLQ--------ELLRDEQEEIESSKQEIEKEEEKLAQVLKENKEEEKEKkLQ 284

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1804876928  570 IMEIKQLQQELQDYQNKLIYLVPEKQLLNERIKNMQLGNT-PDLGIDLLHKKSLEKEELCQRLKEQLDALEKETASKLSE 648
Cdd:pfam02463  285 EEELKLLAKEEEELKSELLKLERRKVDDEEKLKESEKEKKkAEKELKKEKEEIEELEKELKELEIKREAEEEEEEELEKL 364

                          250       260       270       280       290       300       310       320
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1804876928  649 MDSFNNQLKcgNMDDSVLQCLLSLLSCLNNLFLLLKELRESYNTQQLALEQLHKIKRDKLKEIERKRSELIQKKKLEDea 728
Cdd:pfam02463  365 QEKLEQLEE--ELLAKKKLESERLSSAAKLKEEELELKSEEEKEAQLLLELARQLEDLLKEEKKEELEILEEEEESIE-- 440

                          330       340       350       360
                   ....*....|....*....|....*....|....*....|....*..
gi 1804876928  729 irkAKQGKENLWRESLRKEEEEKQKRLQEEKTQEKVQEEERKVEEKQ 775
Cdd:pfam02463  441 ---LKQGKLTEEKEELEKQELKLLKDELELKKSEDLLKETQLVKLQE 484

Src homology 3 domain of Hematopoietic lineage cell-specific protein 1; HS1, also called HCLS1 (hematopoietic cell-specific Lyn substrate 1), is a cortactin homolog expressed specifically in hematopoietic cells. It is an actin regulatory protein that binds the Arp2/3 complex and stabilizes branched actin filaments. It is required for cell spreading and signaling in lymphocytes. It regulates cytoskeletal remodeling that controls lymphocyte trafficking, and it also affects tissue invasion and infiltration of leukemic B cells. Like cortactin, HS1 contains an N-terminal acidic domain, several copies of a repeat domain found in cortactin and HS1, a proline-rich region, and a C-terminal SH3 domain. The N-terminal region binds the Arp2/3 complex and F-actin, while the C-terminal region acts as an adaptor or scaffold that can connect varied proteins that bind the SH3 domain within the actin network. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 213006 [Multi-domain] Cd Length: 55 Bit Score: 59.46 E-value: 5.25e-11

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....*.
gi 1804876928 1150 VCQViAMYDYVANNEDELNFSKGQLINVLNKDDPDWWQGEINGVTGLFPSNYVKMT 1205
Cdd:cd12073      1 ICAV-ALYDYQGEGDDEISFDPQETITDIEMVDEGWWKGTCHGHRGLFPANYVELL 55

Src homology 3 domain of SH3 domain containing Ysc84-like 1 (SH3YL1) protein; SH3YL1 localizes to the plasma membrane and is required for dorsal ruffle formation. It binds phosphoinositides (PIs) with high affinity through its N-terminal SYLF domain (also called DUF500). In addition, SH3YL1 contains a C-terminal SH3 domain which has been reported to bind to N-WASP, dynamin 2, and SHIP2 (a PI 5-phosphatase). SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212775 Cd Length: 54 Bit Score: 58.94 E-value: 7.37e-11

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....
gi 1804876928 1152 QVIAMYDYVANNEDELNFSKGQLINVLNKDDP--DWWQGEINGVTGLFPSNYVK 1203
Cdd:cd11841      1 EVTALYSFEGQQPCDLSFQAGDRITVLTRTDSqfDWWEGRLRGRVGIFPANYVS 54

Src homology 3 domains of the p47phox subunit of NADPH oxidase and similar domains; This family is composed of the tandem SH3 domains of p47phox subunit of NADPH oxidase and Nox Organizing protein 1 (NoxO1), the four SH3 domains of Tks4 (Tyr kinase substrate with four SH3 domains), the five SH3 domains of Tks5, the SH3 domain of obscurin, Myosin-I, and similar domains. Most members of this group also contain Phox homology (PX) domains, except for obscurin and Myosin-I. p47phox and NoxO1 are regulators of the phagocytic NADPH oxidase complex (also called Nox2 or gp91phox) and nonphagocytic NADPH oxidase Nox1, respectively. They play roles in the activation of their respective NADPH oxidase, which catalyzes the transfer of electrons from NADPH to molecular oxygen to form superoxide. Tks proteins are Src substrates and scaffolding proteins that play important roles in the formation of podosomes and invadopodia, the dynamic actin-rich structures that are related to cell migration and cancer cell invasion. Obscurin is a giant muscle protein that plays important roles in the organization and assembly of the myofibril and the sarcoplasmic reticulum. Type I myosins (Myosin-I) are actin-dependent motors in endocytic actin structures and actin patches. They play roles in membrane traffic in endocytic and secretory pathways, cell motility, and mechanosensing. Myosin-I contains an N-terminal actin-activated ATPase, a phospholipid-binding TH1 (tail homology 1) domain, and a C-terminal extension which includes an F-actin-binding TH2 domain, an SH3 domain, and an acidic peptide that participates in activating the Arp2/3complex. The SH3 domain of myosin-I is required for myosin-I-induced actin polymerization. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212790 [Multi-domain] Cd Length: 53 Bit Score: 58.80 E-value: 7.84e-11

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|..
gi 1804876928 1152 QVIAMYDYVANNEDELNFSKGQLINVLNKDDPDWWQGEINGVTGLFPSNYVK 1203
Cdd:cd11856      1 SYVAIADYEAQGDDEISLQEGEVVEVLEKNDSGWWYVRKGDKEGWVPASYLE 52

First Src Homology 3 domain of SH3 domain containing ring finger proteins; This model represents the first SH3 domain of SH3RF1 (or POSH), SH3RF2 (or POSHER), SH3RF3 (POSH2), and similar domains. Members of this family are scaffold proteins that function as E3 ubiquitin-protein ligases. They all contain an N-terminal RING finger domain and multiple SH3 domains; SH3RF1 and SH3RF3 have four SH3 domains while SH3RF2 has three. SH3RF1 plays a role in calcium homeostasis through the control of the ubiquitin domain protein Herp. It may also have a role in regulating death receptor mediated and JNK mediated apoptosis. SH3RF3 interacts with p21-activated kinase 2 (PAK2) and GTP-loaded Rac1. It may play a role in regulating JNK mediated apoptosis in certain conditions. SH3RF2 acts as an anti-apoptotic regulator of the JNK pathway by binding to and promoting the degradation of SH3RF1. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212720 [Multi-domain] Cd Length: 53 Bit Score: 58.91 E-value: 8.01e-11

                           10        20        30        40
                   ....*....|....*....|....*....|....*....|....*....
gi 1804876928 1155 AMYDYVANNEDELNFSKGQLINVLNKDDPDWWQGEINGVTGLFPSNYVK 1203
Cdd:cd11786      4 ALYNYEGKEPGDLSFKKGDIILLRKRIDENWYHGECNGKQGFFPASYVQ 52

Src Homology 3 domain of GTPase Regulator Associated with Focal adhesion kinase and similar proteins; This subfamily is composed of Rho GTPase activating proteins (GAPs) with similarity to GRAF. Members contain an N-terminal BAR domain, followed by a Pleckstrin homology (PH) domain, a Rho GAP domain, and a C-terminal SH3 domain. Although vertebrates harbor four Rho GAPs in the GRAF subfamily including GRAF, GRAF2, GRAF3, and Oligophrenin-1 (OPHN1), only three are included in this model. OPHN1 contains the BAR, PH and GAP domains, but not the C-terminal SH3 domain. GRAF and GRAF2 show GAP activity towards RhoA and Cdc42. GRAF influences Rho-mediated cytoskeletal rearrangements and binds focal adhesion kinase. GRAF2 regulates caspase-activated p21-activated protein kinase-2. The SH3 domain of GRAF and GRAF2 binds PKNbeta, a target of the small GTPase Rho. SH3 domains bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs; they play a role in the regulation of enzymes by intramolecular interactions, changing the subcellular localization of signal pathway components and mediate multiprotein complex assemblies.

Pssm-ID: 212815 [Multi-domain] Cd Length: 54 Bit Score: 58.46 E-value: 1.01e-10

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|..
gi 1804876928  786 KALYRFEARSHDEMSFNSGDIIqVDEKTIGEPGWLYGSFQGNFGWFPCNYVE 837
Cdd:cd11882      3 RALYACKAEDESELSFEPGQII-TNVQPSDEPGWLEGTLNGRTGLIPENYVE 53

Src homology 3 domain of Phospholipase C (PLC) gamma 2; PLCgamma2 is primarily expressed in haematopoietic cells, specifically in B cells. It is activated by tyrosine phosphorylation by B cell receptor (BCR) kinases and is recruited to the plasma membrane where its substrate is located. It is required in pre-BCR signaling and in the maturation of B cells. PLCs catalyze the hydrolysis of phosphatidylinositol (4,5)-bisphosphate [PtdIns(4,5)P2] to produce Ins(1,4,5)P3 and diacylglycerol (DAG). Ins(1,4,5)P3 initiates the calcium signaling cascade while DAG functions as an activator of PKC. PLCgamma contains a Pleckstrin homology (PH) domain followed by an elongation factor (EF) domain, two catalytic regions of PLC domains that flank two tandem SH2 domains, followed by a SH3 domain and C2 domain. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212902 Cd Length: 55 Bit Score: 58.31 E-value: 1.11e-10

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|..
gi 1804876928 1153 VIAMYDYVANNEDELNFSKGQLINVLNKDDPDWWQGEING-VTGLFPSNYVK 1203
Cdd:cd11969      2 VKALYDYRAKRSDELSFCKGALIHNVSKETGGWWKGDYGGkVQHYFPSNYVE 53

Src Homology 3 domain of Pak Interactive eXchange factors; PIX proteins are Rho guanine nucleotide exchange factors (GEFs), which activate small GTPases by exchanging bound GDP for free GTP. They act as GEFs for both Cdc42 and Rac 1, and have been implicated in cell motility, adhesion, neurite outgrowth, and cell polarity. Vertebrates contain two proteins from the PIX subfamily, alpha-PIX and beta-PIX. Alpha-PIX, also called ARHGEF6, is localized in dendritic spines where it regulates spine morphogenesis. Mutations in the ARHGEF6 gene cause X-linked intellectual disability in humans. Beta-PIX play roles in regulating neuroendocrine exocytosis, focal adhesion maturation, cell migration, synaptic vesicle localization, and insulin secretion. PIX proteins contain an N-terminal SH3 domain followed by RhoGEF (also called Dbl-homologous or DH) and Pleckstrin Homology (PH) domains, and a C-terminal leucine-zipper domain for dimerization. The SH3 domain of PIX binds to an atypical PxxxPR motif in p21-activated kinases (PAKs) with high affinity. The binding of PAKs to PIX facilitate the localization of PAKs to focal complexes and also localizes PAKs to PIX targets Cdc43 and Rac, leading to the activation of PAKs. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212810 [Multi-domain] Cd Length: 53 Bit Score: 58.48 E-value: 1.11e-10

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|...
gi 1804876928  923 KAQALCSWTAKKDNHLNFSKHDIITVLEQQE-NWWFGEVHGGRGWFPKSYVKI 974
Cdd:cd11877      1 LVRAKFNFEGTNEDELSFDKGDIITVTQVVEgGWWEGTLNGKTGWFPSNYVKE 53

Src homology 3 domain of Fyn and Yrk Protein Tyrosine Kinases; Fyn and Yrk (Yes-related kinase) are members of the Src subfamily of proteins, which are cytoplasmic (or non-receptor) PTKs. Fyn, together with Lck, plays a critical role in T-cell signal transduction by phosphorylating ITAM (immunoreceptor tyr activation motif) sequences on T-cell receptors, ultimately leading to the proliferation and differentiation of T-cells. In addition, Fyn is involved in the myelination of neurons, and is implicated in Alzheimer's and Parkinson's diseases. Yrk has been detected only in chickens. It is primarily found in neuronal and epithelial cells and in macrophages. It may play a role in inflammation and in response to injury. Src kinases contain an N-terminal SH4 domain with a myristoylation site, followed by SH3 and SH2 domains, a tyr kinase domain, and a regulatory C-terminal region containing a conserved tyr. They are activated by autophosphorylation at the tyr kinase domain, but are negatively regulated by phosphorylation at the C-terminal tyr by Csk (C-terminal Src Kinase). The SH3 domain of Src kinases contributes to substrate recruitment by binding adaptor proteins/substrates, and regulation of kinase activity through an intramolecular interaction. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212939 [Multi-domain] Cd Length: 56 Bit Score: 58.52 E-value: 1.16e-10

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|.
gi 1804876928 1154 IAMYDYVANNEDELNFSKGQLINVLNKDDPDWWQGE--INGVTGLFPSNYV 1202
Cdd:cd12006      4 VALYDYEARTEDDLSFHKGEKFQILNSSEGDWWEARslTTGETGYIPSNYV 54

Second Src Homology 3 domain of Nck adaptor proteins; Nck adaptor proteins regulate actin cytoskeleton dynamics by linking proline-rich effector molecules to protein tyrosine kinases and phosphorylated signaling intermediates. They contain three SH3 domains and a C-terminal SH2 domain. They function downstream of the PDGFbeta receptor and are involved in Rho GTPase signaling and actin dynamics. Vertebrates contain two Nck adaptor proteins: Nck1 (also called Nckalpha) and Nck2 (also called Nckbeta or Growth factor receptor-bound protein 4, Grb4), which show partly overlapping functions but also bind distinct targets. Their SH3 domains are involved in recruiting downstream effector molecules, such as the N-WASP/Arp2/3 complex, which when activated induces actin polymerization that results in the production of pedestals, or protrusions of the plasma membrane. The second SH3 domain of Nck appears to prefer ligands containing the APxxPxR motif. SH3 domains are protein interaction domains that usually bind to proline-rich ligands with moderate affinity and selectivity, preferentially a PxxP motif. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212700 [Multi-domain] Cd Length: 53 Bit Score: 58.05 E-value: 1.29e-10

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|
gi 1804876928  789 YRFEARSHDEMSFNSGDIIQVDEKTigEPGWLYGSFQGNFGWFPCNYVEK 838
Cdd:cd11766      6 FNYEAQREDELSLRKGDRVLVLEKS--SDGWWRGECNGQVGWFPSNYVTE 53

SH3 domain; SH3 (Src homology 3) domains are often indicative of a protein involved in signal transduction related to cytoskeletal organization. First described in the Src cytoplasmic tyrosine kinase. The structure is a partly opened beta barrel.

Pssm-ID: 394975 [Multi-domain] Cd Length: 47 Bit Score: 57.98 E-value: 1.45e-10

                           10        20        30        40
                   ....*....|....*....|....*....|....*....|....*..
gi 1804876928 1008 IALYSYSSVEPGDLTFIEGEEILVTQK-DGEWWTG-SIGDRTGIFPS 1052
Cdd:pfam00018    1 VALYDYTAQEPDELSFKKGDIIIVLEKsEDGWWKGrNKGGKEGLIPS 47

Second Src Homology 3 domain of FCH and double SH3 domains protein 2; FCHSD2 has a domain structure consisting of an N-terminal F-BAR (FES-CIP4 Homology and Bin/Amphiphysin/Rvs), two SH3, and C-terminal proline-rich domains. It has only been characterized in silico and its function is unknown. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212827 Cd Length: 56 Bit Score: 58.03 E-value: 1.65e-10

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....
gi 1804876928 1153 VIAMYDYVANNEDELNFSKGQLINVLNKDDPD---WWQGEINGVTGLFPSNYVK 1203
Cdd:cd11894      2 VKALYDYEGQTDDELSFPEGAIIRILNKENQDddgFWEGEFNGRIGVFPSVLVE 55

N-terminal Src homology 3 domain of GRB2-related adaptor protein; GRAP is a GRB-2 like adaptor protein that is highly expressed in lymphoid tissues. It acts as a negative regulator of T cell receptor (TCR)-induced lymphocyte proliferation by downregulating the signaling to the Ras/ERK pathway. It has been identified as a regulator of TGFbeta signaling in diabetic kidney tubules and may have a role in the pathogenesis of the disease. GRAP contains an N-terminal SH3 domain, a central SH2 domain, and a C-terminal SH3 domain. The N-terminal SH3 domain of the related protein GRB2 binds to Sos and Sos-derived proline-rich peptides. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212881 [Multi-domain] Cd Length: 54 Bit Score: 57.90 E-value: 1.65e-10

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....
gi 1804876928 1152 QVIAMYDYVANNEDELNFSKGQLINVLN-KDDPDWWQGEINGVTGLFPSNYVKM 1204
Cdd:cd11948      1 EAVALYSFQATESDELPFQKGDILKILNmEDDQNWYKAELQGREGYIPKNYIKV 54

MAEBL; Provisional

Pssm-ID: 173412 [Multi-domain] Cd Length: 2084 Bit Score: 66.32 E-value: 1.81e-10

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1804876928  388 EEEPQKKLPVTFEDKRKANYER--GNVELEKRRQAlMEQQQREAERKAQK-EKEEWERKQRELQE--QEWKKQLELEKRL 462
Cdd:PTZ00121  1246 EEERNNEEIRKFEEARMAHFARrqAAIKAEEARKA-DELKKAEEKKKADEaKKAEEKKKADEAKKkaEEAKKADEAKKKA 1324

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1804876928  463 EKQRELERQREEERRKEIERREAAKQELERQRRlEWERIRRQELLNQRNREQEEIVRLNSKKKSLHL-ELEALNGKHQQI 541
Cdd:PTZ00121  1325 EEAKKKADAAKKKAEEAKKAAEAAKAEAEAAAD-EAEAAEEKAEAAEKKKEEAKKKADAAKKKAEEKkKADEAKKKAEED 1403

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1804876928  542 SGRLQDVRlRKQTQKTEIEVLDKQCDlEIMEIKQLQQELQDYQ--NKLIYLVPEKQLLNERIKNMQLGNTPD-------- 611
Cdd:PTZ00121  1404 KKKADELK-KAAAAKKKADEAKKKAE-EKKKADEAKKKAEEAKkaDEAKKKAEEAKKAEEAKKKAEEAKKADeakkkaee 1481

                          250       260       270       280       290       300       310       320
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1804876928  612 -LGIDLLHKKSLEKEELCQRLKEQLDALEKETASKLSEMDSFNNQLKCGNMDDSVLQCLLSLLSCLNNLFLLLKELRESY 690
Cdd:PTZ00121  1482 aKKADEAKKKAEEAKKKADEAKKAAEAKKKADEAKKAEEAKKADEAKKAEEAKKADEAKKAEEKKKADELKKAEELKKAE 1561

                          330       340       350       360       370       380       390       400
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1804876928  691 NTQQlaLEQLHKIKRDK---------LKEIERKRSELIQK-----KKLEDEAIRKAKQGKENlwRESLRKEEEEKQKRLQ 756
Cdd:PTZ00121  1562 EKKK--AEEAKKAEEDKnmalrkaeeAKKAEEARIEEVMKlyeeeKKMKAEEAKKAEEAKIK--AEELKKAEEEKKKVEQ 1637

                          410
                   ....*....|....*..
gi 1804876928  757 EEKTQEkvqEEERKVEE 773
Cdd:PTZ00121  1638 LKKKEA---EEKKKAEE 1651

Fifth Src homology 3 domain of ADAM-binding protein Eve-1; Eve-1, also called SH3 domain-containing protein 19 (SH3D19) or EEN-binding protein (EBP), exists in multiple alternatively spliced isoforms. The longest isoform contains five SH3 domain in the C-terminal region and seven proline-rich motifs in the N-terminal region. It is abundantly expressed in skeletal muscle and heart, and may be involved in regulating the activity of ADAMs (A disintegrin and metalloproteases). Eve-1 interacts with EEN, an endophilin involved in endocytosis and may be the target of the MLL-EEN fusion protein that is implicated in leukemogenesis. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212752 [Multi-domain] Cd Length: 50 Bit Score: 57.49 E-value: 1.94e-10

                           10        20        30        40
                   ....*....|....*....|....*....|....*....|....*..
gi 1804876928 1155 AMYDYVANNEDELNFSKGQLINVLNKDDPDWWQGEINGVTGLFPSNY 1201
Cdd:cd11818      4 ALYDFTGENEDELSFKAGDIITELESIDEEWMSGELRGKSGIFPKNF 50

C-terminal (or second) Src homology 3 domain of VAV proteins; VAV proteins function both as cytoplasmic guanine nucleotide exchange factors (GEFs) for Rho GTPases and scaffold proteins and they play important roles in cell signaling by coupling cell surface receptors to various effector functions. They play key roles in processes that require cytoskeletal reorganization including immune synapse formation, phagocytosis, cell spreading, and platelet aggregation, among others. Vertebrates have three VAV proteins (VAV1, VAV2, and VAV3). VAV proteins contain several domains that enable their function: N-terminal calponin homology (CH), acidic, RhoGEF (also called Dbl-homologous or DH), Pleckstrin Homology (PH), C1 (zinc finger), SH2, and two SH3 domains. The SH3 domain of VAV is involved in the localization of proteins to specific sites within the cell, by interacting with proline-rich sequences within target proteins. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212764 [Multi-domain] Cd Length: 54 Bit Score: 57.64 E-value: 2.02e-10

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|.
gi 1804876928 1154 IAMYDYVANNEDELNFSKGQLINVLNK-DDPDWWQGEINGVTGLFPSNYVK 1203
Cdd:cd11830      3 KARYDFCARDMRELSLKEGDVVKIYNKkGQQGWWRGEINGRIGWFPSTYVE 53

DNA double-strand break repair ATPase Rad50;

Pssm-ID: 235175 [Multi-domain] Cd Length: 880 Bit Score: 65.86 E-value: 2.17e-10

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1804876928  371 KQIDSINGTLPSYQKIQE--EEPQKKLPVTFEDKRKANYERGNVELEKRRQALMEQQQREAERKAQKEKEEWERKQRELQ 448
Cdd:PRK03918   207 REINEISSELPELREELEklEKEVKELEELKEEIEELEKELESLEGSKRKLEEKIRELEERIEELKKEIEELEEKVKELK 286

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1804876928  449 EQEWKKQ--LELEKRLEKQRElerqreeerrkeierreaAKQELE-RQRRLEWERIRRQELLNQRNREQEEIVRLNSKKK 525
Cdd:PRK03918   287 ELKEKAEeyIKLSEFYEEYLD------------------ELREIEkRLSRLEEEINGIEERIKELEEKEERLEELKKKLK 348

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1804876928  526 SLHLELEALNGKHQ------QISGRLQdvRLRKQTQKTEIEVLDKqcdlEIMEIKQLQQELQDYQNKLIYLVPE-KQLLN 598
Cdd:PRK03918   349 ELEKRLEELEERHElyeeakAKKEELE--RLKKRLTGLTPEKLEK----ELEELEKAKEEIEEEISKITARIGElKKEIK 422

                          250       260       270       280       290       300       310       320
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1804876928  599 ERIKNMQ-----LGNTPDLG--IDLLHKKSL----------------EKEELCQRLKEQLDALEKETA--SKLSEMDSFN 653
Cdd:PRK03918   423 ELKKAIEelkkaKGKCPVCGreLTEEHRKELleeytaelkriekelkEIEEKERKLRKELRELEKVLKkeSELIKLKELA 502

                          330       340       350       360       370       380       390       400
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1804876928  654 NQLKcgNMDDSVLQCLLSLLSCLNNLFLLLKELRESYNTQQLALE-QLHKIK---------RDKLKEIERKRSELiqKKK 723
Cdd:PRK03918   503 EQLK--ELEEKLKKYNLEELEKKAEEYEKLKEKLIKLKGEIKSLKkELEKLEelkkklaelEKKLDELEEELAEL--LKE 578

                          410       420       430       440       450       460       470
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 1804876928  724 LEDEAIRKAKQGKENL------WRESLR--------KEEEEKQKRLQEE--KTQEKVQEEERKVEEKQCEPASALVNY 785
Cdd:PRK03918   579 LEELGFESVEELEERLkelepfYNEYLElkdaekelEREEKELKKLEEEldKAFEELAETEKRLEELRKELEELEKKY 656

Src homology 3 domain of Abl Interactor proteins; Abl interactor (Abi) proteins are adaptor proteins serving as binding partners and substrates of Abl tyrosine kinases. They are involved in regulating actin cytoskeletal reorganization and play important roles in membrane-ruffling, endocytosis, cell motility, and cell migration. They localize to sites of actin polymerization in epithelial adherens junction and immune synapses, as well as to the leading edge of lamellipodia. Vertebrates contain two Abi proteins, Abi1 and Abi2. Abi1 displays a wide expression pattern while Abi2 is highly expressed in the eye and brain. Abi proteins contain a homeobox homology domain, a proline-rich region, and a SH3 domain. The SH3 domain of Abi binds to a PxxP motif in Abl. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212760 [Multi-domain] Cd Length: 52 Bit Score: 57.72 E-value: 2.20e-10

                           10        20        30        40
                   ....*....|....*....|....*....|....*....|....*....
gi 1804876928 1008 IALYSYSSVEPGDLTFIEGEEILVTQKDGE-WWTGSIGDRTGIFPSNYV 1055
Cdd:cd11826      3 VALYDYTADKDDELSFQEGDIIYVTKKNDDgWYEGVLNGVTGLFPGNYV 51

chromosome segregation protein SMC, primarily archaeal type; SMC (structural maintenance of chromosomes) proteins bind DNA and act in organizing and segregating chromosomes for partition. SMC proteins are found in bacteria, archaea, and eukaryotes. It is found in a single copy and is homodimeric in prokaryotes, but six paralogs (excluded from this family) are found in eukarotes, where SMC proteins are heterodimeric. This family represents the SMC protein of archaea and a few bacteria (Aquifex, Synechocystis, etc); the SMC of other bacteria is described by TIGR02168. The N- and C-terminal domains of this protein are well conserved, but the central hinge region is skewed in composition and highly divergent. [Cellular processes, Cell division, DNA metabolism, Chromosome-associated proteins]

Pssm-ID: 274009 [Multi-domain] Cd Length: 1164 Bit Score: 65.86 E-value: 2.37e-10

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1804876928  400 EDKRKANYERGNVELEKRRQALMEQQQREAERKAQKEKEEWERKQ---RELQEQEWKKQLELEKRLEKQRELERQREEER 476
Cdd:TIGR02169  170 RKKEKALEELEEVEENIERLDLIIDEKRQQLERLRREREKAERYQallKEKREYEGYELLKEKEALERQKEAIERQLASL 249

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1804876928  477 RKEierrEAAKQELERQRRLEWERIRRqeLLNQRNRE-----QEEIVRLNSKKKSLHLELEALNGKHQQISGRLQDvrLR 551
Cdd:TIGR02169  250 EEE----LEKLTEEISELEKRLEEIEQ--LLEELNKKikdlgEEEQLRVKEKIGELEAEIASLERSIAEKERELED--AE 321

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1804876928  552 KQTQKTEIEvLDKQcdleIMEIKQLQQELQDYQNKLIYLVPEKQLLNERiknmqlgntpdlgIDLLHKKSLEKEELCQRL 631
Cdd:TIGR02169  322 ERLAKLEAE-IDKL----LAEIEELEREIEEERKRRDKLTEEYAELKEE-------------LEDLRAELEEVDKEFAET 383

                          250       260       270       280       290       300       310       320
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1804876928  632 KEQLDALEKETASKLSEMDSFNNQLkcgnmdDSVLQCLLSLLSCLNNLFLLLKELREsyntQQLALEQLHKIKRDKLKEI 711
Cdd:TIGR02169  384 RDELKDYREKLEKLKREINELKREL------DRLQEELQRLSEELADLNAAIAGIEA----KINELEEEKEDKALEIKKQ 453

                          330       340       350       360       370
                   ....*....|....*....|....*....|....*....|....*....|....*..
gi 1804876928  712 ERKRSELIQKKKLEDEAIRKAKQGKenlwrESLRKEEEEKQKRLQEEKTQEKVQEEE 768
Cdd:TIGR02169  454 EWKLEQLAADLSKYEQELYDLKEEY-----DRVEKELSKLQRELAEAEAQARASEER 505

First Src Homology 3 domain of the fungal endocytic adaptor protein Sla1p; Sla1p facilitates endocytosis by playing a role as an adaptor protein in coupling components of the actin cytoskeleton to the endocytic machinery. It interacts with Abp1p, Las17p and Pan1p, which are activator proteins of actin-related protein 2/3 (Arp2/3). Sla1p contains multiple domains including three SH3 domains, a SAM (sterile alpha motif) domain, and a Sla1 homology domain 1 (SHD1), which binds to the NPFXD motif that is found in many integral membrane proteins such as the Golgi-localized Arf-binding protein Lsb5p and the P4-ATPases, Drs2p and Dnf1p. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212707 [Multi-domain] Cd Length: 57 Bit Score: 57.43 E-value: 2.40e-10

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....
gi 1804876928 1155 AMYDYVANNEDELNFSKGQLINVLNKDDPDWWQGEINGVT-------GLFPSNY 1201
Cdd:cd11773      4 ALYDYEPQTEDELTIQEDDILYLLEKSDDDWWKVKLKVNSsdddepvGLVPATY 57

First Src homology 3 domain (or SH3A) of Intersectin; Intersectins (ITSNs) are adaptor proteins that function in exo- and endocytosis, actin cytoskeletal reorganization, and signal transduction. They are essential for initiating clathrin-coated pit formation. They bind to many proteins through their multidomain structure and facilitate the assembly of multimeric complexes. Vertebrates contain two ITSN proteins, ITSN1 and ITSN2, which exist in alternatively spliced short and long isoforms. The short isoforms contain two Eps15 homology domains (EH1 and EH2), a coiled-coil region and five SH3 domains (SH3A-E), while the long isoforms, in addition, contain RhoGEF (also called Dbl-homologous or DH), Pleckstrin homology (PH) and C2 domains. ITSN1 and ITSN2 are both widely expressed, with variations depending on tissue type and stage of development. The first SH3 domain (or SH3A) of ITSN1 has been shown to bind many proteins including Sos1, dynamin1/2, CIN85, c-Cbl, PI3K-C2, SHIP2, N-WASP, and CdGAP, among others. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212770 [Multi-domain] Cd Length: 55 Bit Score: 57.37 E-value: 2.45e-10

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|
gi 1804876928 1155 AMYDYVANNEDELNFSKGQLINVLNKDD--PDWWQGEINGVTGLFPSNYV 1202
Cdd:cd11836      4 ALYAFEARNPDEISFQPGDIIQVDESQVaePGWLAGELKGKTGWFPANYV 53

Src homology 3 domain of ARHGEF9-like Rho guanine nucleotide exchange factors; Members of this family contain a SH3 domain followed by RhoGEF (also called Dbl-homologous or DH) and Pleckstrin Homology (PH) domains. They include the Rho guanine nucleotide exchange factors ARHGEF9, ASEF (also called ARHGEF4), ASEF2, and similar proteins. GEFs activate small GTPases by exchanging bound GDP for free GTP. ARHGEF9 specifically activates Cdc42, while both ASEF and ASEF2 can activate Rac1 and Cdc42. ARHGEF9 is highly expressed in the brain and it interacts with gephyrin, a postsynaptic protein associated with GABA and glycine receptors. ASEF plays a role in angiogenesis and cell migration. ASEF2 is important in cell migration and adhesion dynamics. ASEF exists in an autoinhibited form and is activated upon binding of the tumor suppressor APC (adenomatous polyposis coli), leading to the activation of Rac1 or Cdc42. In its autoinhibited form, the SH3 domain of ASEF forms an extensive interface with the DH and PH domains, blocking the Rac binding site. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212762 [Multi-domain] Cd Length: 53 Bit Score: 57.39 E-value: 2.60e-10

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|..
gi 1804876928 1153 VIAMYDYVANNEDELNFSKGQLINVLNKDDPDWWQGEINGVTGLFPSNYVKM 1204
Cdd:cd11828      2 AEALWDHVTMDPEELGFKAGDVIEVLDMSDKDWWWGSIRDEEGWFPASFVRL 53

First C-terminal Src homology 3 domain of SH3 and cysteine-rich domain-containing (Stac) proteins; Stac proteins are putative adaptor proteins that contain a cysteine-rich C1 domain and one or two SH3 domains at the C-terminus. There are three mammalian members (Stac1, Stac2, and Stac3) of this family. Stac1 and Stac3 contain two SH3 domains while Stac2 contains a single SH3 domain at the C-terminus. This model represents the first C-terminal SH3 domain of Stac1 and Stac3, and the single C-terminal SH3 domain of Stac2. Stac1 and Stac2 have been found to be expressed differently in mature dorsal root ganglia (DRG) neurons. Stac1 is mainly expressed in peptidergic neurons while Stac2 is found in a subset of nonpeptidergic and all trkB+ neurons. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212767 [Multi-domain] Cd Length: 53 Bit Score: 57.51 E-value: 2.62e-10

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|
gi 1804876928 1007 YIALYSYSSVEPGDLTFIEGEEILVTQ-KDGEWWTGSIGDRTGIFPSNYV 1055
Cdd:cd11833      2 YVALYKFKPQENEDLEMRPGDKITLLDdSNEDWWKGKIEDRVGFFPANFV 51

Src homology 3 domain of Protein kinase C and Casein kinase Substrate in Neurons (PACSIN) proteins; PACSINs, also called Synaptic dynamin-associated proteins (Syndapins), act as regulators of cytoskeletal and membrane dynamics. They bind both dynamin and Wiskott-Aldrich syndrome protein (WASP), and may provide direct links between the actin cytoskeletal machinery through WASP and dynamin-dependent endocytosis. Vetebrates harbor three isoforms with distinct expression patterns and specific functions. PACSINs contain an N-terminal F-BAR domain and a C-terminal SH3 domain. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212777 [Multi-domain] Cd Length: 53 Bit Score: 57.43 E-value: 2.64e-10

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|.
gi 1804876928 1153 VIAMYDYVANNEDELNFSKGQLINVL-NKDDPDWWQGEINGVTGLFPSNYV 1202
Cdd:cd11843      2 VRALYDYEGQESDELSFKAGDILTKLeEEDEQGWCKGRLDGRVGLYPANYV 52

First Src Homology 3 domain of SH3 domain containing ring finger proteins; This model represents the first SH3 domain of SH3RF1 (or POSH), SH3RF2 (or POSHER), SH3RF3 (POSH2), and similar domains. Members of this family are scaffold proteins that function as E3 ubiquitin-protein ligases. They all contain an N-terminal RING finger domain and multiple SH3 domains; SH3RF1 and SH3RF3 have four SH3 domains while SH3RF2 has three. SH3RF1 plays a role in calcium homeostasis through the control of the ubiquitin domain protein Herp. It may also have a role in regulating death receptor mediated and JNK mediated apoptosis. SH3RF3 interacts with p21-activated kinase 2 (PAK2) and GTP-loaded Rac1. It may play a role in regulating JNK mediated apoptosis in certain conditions. SH3RF2 acts as an anti-apoptotic regulator of the JNK pathway by binding to and promoting the degradation of SH3RF1. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212720 [Multi-domain] Cd Length: 53 Bit Score: 57.37 E-value: 2.72e-10

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|..
gi 1804876928  924 AQALCSWTAKKDNHLNFSKHDIITVLEQ-QENWWFGEVHGGRGWFPKSYVKI 974
Cdd:cd11786      2 AKALYNYEGKEPGDLSFKKGDIILLRKRiDENWYHGECNGKQGFFPASYVQV 53

Src Homology 3 domain of Mixed Lineage Kinases; MLKs are Serine/Threonine Kinases (STKs), catalyzing the transfer of the gamma-phosphoryl group from ATP to S/T residues on protein substrates. MLKs act as mitogen-activated protein kinase kinase kinases (MAP3Ks, MKKKs, MAPKKKs), which phosphorylate and activate MAPK kinases (MAPKKs or MKKs or MAP2Ks), which in turn phosphorylate and activate MAPKs during signaling cascades that are important in mediating cellular responses to extracellular signals. MLKs play roles in immunity and inflammation, as well as in cell death, proliferation, and cell cycle regulation. Mammals have four MLKs (MLK1-4), mostly conserved in vertebrates, which contain an SH3 domain, a catalytic kinase domain, a leucine zipper, a proline-rich region, and a CRIB domain that mediates binding to GTP-bound Cdc42 and Rac. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212809 [Multi-domain] Cd Length: 58 Bit Score: 57.14 E-value: 3.33e-10

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....*..
gi 1804876928 1007 YIALYSYSSVEPGDLTFIEGEEILVTQKDGE------WWTGSIGDRTGIFPSNYVKP 1057
Cdd:cd11876      2 WTALFDYDARGEDELTLRRGQPVEVLSKDAAvsgdegWWTGKIGDKVGIFPSNYVAP 58

MAEBL; Provisional

Pssm-ID: 173412 [Multi-domain] Cd Length: 2084 Bit Score: 65.55 E-value: 3.35e-10

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1804876928  400 EDKRKANYERGNVELEKRRQALMEQQQREAERkaQKEKEEWERKQRELQ---EQEWKKQLELEKRLEKQRELERQREEER 476
Cdd:PTZ00121  1275 EEARKADELKKAEEKKKADEAKKAEEKKKADE--AKKKAEEAKKADEAKkkaEEAKKKADAAKKKAEEAKKAAEAAKAEA 1352

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1804876928  477 RKEIERREAAKQELERQRRLEWERIRRQELLNQRNREQEEIVRLnsKKKSLHLELEALNGKHQQISGRLQDVRLRKQTQK 556
Cdd:PTZ00121  1353 EAAADEAEAAEEKAEAAEKKKEEAKKKADAAKKKAEEKKKADEA--KKKAEEDKKKADELKKAAAAKKKADEAKKKAEEK 1430

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1804876928  557 TEIEVLDKQCD--LEIMEIKQLQQELQDYQNkLIYLVPEKQLLNERIKNMQLGNTPDLgidlLHKKSLEKEELCQRLKEQ 634
Cdd:PTZ00121  1431 KKADEAKKKAEeaKKADEAKKKAEEAKKAEE-AKKKAEEAKKADEAKKKAEEAKKADE----AKKKAEEAKKKADEAKKA 1505

                          250       260       270       280       290       300       310       320
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1804876928  635 LDALEKETASKLSEMDSFNNQLKCGNMDDSVLQCLLSLLSCLNNLFLLLKELRESYNTQQLalEQLHKIKRDK------- 707
Cdd:PTZ00121  1506 AEAKKKADEAKKAEEAKKADEAKKAEEAKKADEAKKAEEKKKADELKKAEELKKAEEKKKA--EEAKKAEEDKnmalrka 1583

                          330       340       350       360       370       380       390       400
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1804876928  708 --LKEIERKRSELIQK-----KKLEDEAIRKAKQGKENlwRESLRKEEEEKQKRLQ-------EEKTQEKVQ--EEERKV 771
Cdd:PTZ00121  1584 eeAKKAEEARIEEVMKlyeeeKKMKAEEAKKAEEAKIK--AEELKKAEEEKKKVEQlkkkeaeEKKKAEELKkaEEENKI 1661


                   ....
gi 1804876928  772 EEKQ 775
Cdd:PTZ00121  1662 KAAE 1665

DNA double-strand break repair ATPase Rad50;

Pssm-ID: 235175 [Multi-domain] Cd Length: 880 Bit Score: 65.09 E-value: 3.64e-10

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1804876928  402 KRKANYERGNV-----ELEKRRQALMEQQQREAERKAQKEKEEWERKQ--RELQEQEWK-----KQLELEKRLEKQRELE 469
Cdd:PRK03918   379 KRLTGLTPEKLekeleELEKAKEEIEEEISKITARIGELKKEIKELKKaiEELKKAKGKcpvcgRELTEEHRKELLEEYT 458

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1804876928  470 RQREEERRKEIERREAAKQELERQRRLEWERIRRQELLNQRnREQEEIVRLNSKKKSLHLE-LEALNGKHQQISGRLQDV 548
Cdd:PRK03918   459 AELKRIEKELKEIEEKERKLRKELRELEKVLKKESELIKLK-ELAEQLKELEEKLKKYNLEeLEKKAEEYEKLKEKLIKL 537

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1804876928  549 rlrkqtqKTEIEVLDKqcdlEIMEIKQLQQELQDYQNKLIYLVPEKQLLNERIKNMQLGNTPDLGIDL-----LHKKSLE 623
Cdd:PRK03918   538 -------KGEIKSLKK----ELEKLEELKKKLAELEKKLDELEEELAELLKELEELGFESVEELEERLkelepFYNEYLE 606

                          250       260       270       280       290       300       310       320
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1804876928  624 ----------KEELCQRLKEQLDALEKETASKLSEMDSFNNQLKcgnmddsvlqcllsllsclnnlflllkELRESYNtq 693
Cdd:PRK03918   607 lkdaekelerEEKELKKLEEELDKAFEELAETEKRLEELRKELE---------------------------ELEKKYS-- 657

                          330       340       350       360       370       380       390       400
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1804876928  694 qlalEQLHKIKRDKL----KEIERKRSELIQKKKLEDEAIRKAKQGKENLwreslrKEEEEKQKRLQE-EKTQEKVQEEE 768
Cdd:PRK03918   658 ----EEEYEELREEYlelsRELAGLRAELEELEKRREEIKKTLEKLKEEL------EEREKAKKELEKlEKALERVEELR 727


                   ....*
gi 1804876928  769 RKVEE 773
Cdd:PRK03918   728 EKVKK 732

Trichohyalin-plectin-homology domain; This family is a mixtrue of two different families of eukaryotic proteins. Trichoplein or mitostatin, was first defined as a meiosis-specific nuclear structural protein. It has since been linked with mitochondrial movement. It is associated with the mitochondrial outer membrane, and over-expression leads to reduction in mitochondrial motility whereas lack of it enhances mitochondrial movement. The activity appears to be mediated through binding the mitochondria to the actin intermediate filaments (IFs). The family is in the trichohyalin-plectin-homology domain.

Pssm-ID: 464007 [Multi-domain] Cd Length: 341 Bit Score: 63.40 E-value: 3.89e-10

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1804876928  415 EKRRQALMEQQQREAERKAQKEKEEWERKQRELQEQEWKKQLElEKRLEKQrelerqreeerrkeierREAAKQELERQR 494
Cdd:pfam13868   41 EERRLDEMMEEERERALEEEEEKEEERKEERKRYRQELEEQIE-EREQKRQ-----------------EEYEEKLQEREQ 102

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1804876928  495 RLE-WERIRRQELLNQRNREQeeivrlnsKKKSLHLELEALNgkhqqisgRLQDVRLRKQTQKTEIEvldkqcDLEIME- 572
Cdd:pfam13868  103 MDEiVERIQEEDQAEAEEKLE--------KQRQLREEIDEFN--------EEQAEWKELEKEEEREE------DERILEy 160

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1804876928  573 IKQLQQELQDYQNKLIYLVPEKQLLNERIKNMQLgntpdlgiDLLHKKSlEKEELCQRL-----KEQLDALEKETASKLS 647
Cdd:pfam13868  161 LKEKAEREEEREAEREEIEEEKEREIARLRAQQE--------KAQDEKA-ERDELRAKLyqeeqERKERQKEREEAEKKA 231

                          250       260       270       280       290       300       310       320
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1804876928  648 EMdsfnnqlkcgnmddsvlqcllsllsclnnlfllLKELRESYnTQQLALEQLHK---IKRDKL--KEIERKRSELIQKK 722
Cdd:pfam13868  232 RQ---------------------------------RQELQQAR-EEQIELKERRLaeeAEREEEefERMLRKQAEDEEIE 277

                          330       340       350       360       370
                   ....*....|....*....|....*....|....*....|....*....|....*....
gi 1804876928  723 KLEDEAIRKAKQGK----ENLWRESLRKEEEEKQKRLQEEKTQEKVQEEERKV--EEKQ 775
Cdd:pfam13868  278 QEEAEKRRMKRLEHrrelEKQIEEREEQRAAEREEELEEGERLREEEAERRERieEERQ 336

Src homology 3 domain of Phospholipase C (PLC) gamma 1; PLCgamma1 is widely expressed and is essential in growth and development. It is activated by the TrkA receptor tyrosine kinase and functions as a key regulator of cell differentiation. It is also the predominant PLCgamma in T cells and is required for T cell and NK cell function. PLCs catalyze the hydrolysis of phosphatidylinositol (4,5)-bisphosphate [PtdIns(4,5)P2] to produce Ins(1,4,5)P3 and diacylglycerol (DAG). Ins(1,4,5)P3 initiates the calcium signaling cascade while DAG functions as an activator of PKC. PLCgamma contains a Pleckstrin homology (PH) domain followed by an elongation factor (EF) domain, two catalytic regions of PLC domains that flank two tandem SH2 domains, followed by a SH3 domain and C2 domain. The SH3 domain of PLCgamma1 directly interacts with dynamin-1 and can serve as a guanine nucleotide exchange factor (GEF). It also interacts with Cbl, inhibiting its phosphorylation and activity. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212903 Cd Length: 60 Bit Score: 57.31 E-value: 3.95e-10

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....
gi 1804876928 1151 CQVIAMYDYVANNEDELNFSKGQLINVLNKDDPDWWQGEINGVTGL-FPSNYVK 1203
Cdd:cd11970      4 CAVKALFDYKAQREDELTFTKNAIIQNVEKQEGGWWRGDYGGKKQLwFPSNYVE 57

Src Homology 3 domain of Sorting Nexin 9 and similar proteins; Sorting nexins (SNXs) are Phox homology (PX) domain containing proteins that are involved in regulating membrane traffic and protein sorting in the endosomal system. SNXs differ from each other in their lipid-binding specificity, subcellular localization and specific function in the endocytic pathway. This subfamily consists of SH3 domain containing SNXs including SNX9, SNX18, SNX33, and similar proteins. SNX9 is localized to plasma membrane endocytic sites and acts primarily in clathrin-mediated endocytosis, while SNX18 is localized to peripheral endosomal structures, and acts in a trafficking pathway that is clathrin-independent but relies on AP-1 and PACS1. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212697 [Multi-domain] Cd Length: 55 Bit Score: 56.95 E-value: 4.38e-10

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|...
gi 1804876928 1152 QVIAMYDYVANNEDELNFSKGQLINVLNKDDPD-WWQGE-INGVTGLFPSNYV 1202
Cdd:cd11763      1 KVRALYDFDSQPSGELSLRAGEVLTITRQDVGDgWLEGRnSRGEVGLFPSSYV 53

RecF/RecN/SMC N terminal domain; This domain is found at the N terminus of SMC proteins. The SMC (structural maintenance of chromosomes) superfamily proteins have ATP-binding domains at the N- and C-termini, and two extended coiled-coil domains separated by a hinge in the middle. The eukaryotic SMC proteins form two kind of heterodimers: the SMC1/SMC3 and the SMC2/SMC4 types. These heterodimers constitute an essential part of higher order complexes, which are involved in chromatin and DNA dynamics. This family also includes the RecF and RecN proteins that are involved in DNA metabolism and recombination.

Pssm-ID: 426784 [Multi-domain] Cd Length: 1161 Bit Score: 64.61 E-value: 5.07e-10

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1804876928  411 NVELEKRRQALMEQQQREAERKAQKEKEEWERKQRELQEQEwKKQLELEKRLEKQRELERQREEERRKEIERREAAKQEl 490
Cdd:pfam02463  667 SLSELTKELLEIQELQEKAESELAKEEILRRQLEIKKKEQR-EKEELKKLKLEAEELLADRVQEAQDKINEELKLLKQK- 744

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1804876928  491 ERQRRLEWERIRRQELLNQRNREQEEIVRLNSKKKSLHLELEALNGKHQQISGRLQDVRLRKQTQKTEIEVLDKQCDLEI 570
Cdd:pfam02463  745 IDEEEEEEEKSRLKKEEKEEEKSELSLKEKELAEEREKTEKLKVEEEKEEKLKAQEEELRALEEELKEEAELLEEEQLLI 824

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1804876928  571 MEIKQLQQELQDYQNKLIYLVPEKQLLNERIKNMQLGNTpdLGIDLLHKKSLEKEELCQRLKEQLDALEKETASKLSEMD 650
Cdd:pfam02463  825 EQEEKIKEEELEELALELKEEQKLEKLAEEELERLEEEI--TKEELLQELLLKEEELEEQKLKDELESKEEKEKEEKKEL 902

                          250       260       270       280       290       300       310       320
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1804876928  651 SFNNQLKCgnmddsvlqcllsllsclnnlfllLKELRESYNTQQLALEQLhkikrDKLKEIERKRSELIQKKKLEDEAIR 730
Cdd:pfam02463  903 EEESQKLN------------------------LLEEKENEIEERIKEEAE-----ILLKYEEEPEELLLEEADEKEKEEN 953

                          330       340       350       360
                   ....*....|....*....|....*....|....*....|....*
gi 1804876928  731 KAKQGKENLWRESLRKEEEEKQKRLQEEKTQEKVQEEERKVEEKQ 775
Cdd:pfam02463  954 NKEEEEERNKRLLLAKEELGKVNLMAIEEFEEKEERYNKDELEKE 998

Uncharacterized conserved protein YhaN, contains AAA domain [Function unknown];

Pssm-ID: 443752 [Multi-domain] Cd Length: 641 Bit Score: 64.40 E-value: 5.10e-10

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1804876928  413 ELEKRRQALMEQQQREAE-RKAQKEKEEWERKQRELQEQEWKKQLELEkRLEKQRELERQREEERrkeierreAAKQELE 491
Cdd:COG4717     72 ELKELEEELKEAEEKEEEyAELQEELEELEEELEELEAELEELREELE-KLEKLLQLLPLYQELE--------ALEAELA 142

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1804876928  492 R-QRRLEWERIRRQELLNQRNREQEEIVRLNSKKKSLHLELEALNGKH----QQISGRLQDVRLRKQTQKTEIEVLDKqc 566
Cdd:COG4717    143 ElPERLEELEERLEELRELEEELEELEAELAELQEELEELLEQLSLATeeelQDLAEELEELQQRLAELEEELEEAQE-- 220

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1804876928  567 dleimEIKQLQQELQDYQNKLIYLVPEKQLlnERIKNMQLGNTPDLGIDLLHKKSLEKEE--------LCQRLKEQLDAL 638
Cdd:COG4717    221 -----ELEELEEELEQLENELEAAALEERL--KEARLLLLIAAALLALLGLGGSLLSLILtiagvlflVLGLLALLFLLL 293

                          250       260       270       280       290       300       310       320
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1804876928  639 EKETASKLSEMDSFNNQLKCGNMDD-SVLQCLLSLLSCLNNLFLLLKELRESYNTQQLALEQLHKIKRD-KLKEIERKRS 716
Cdd:COG4717    294 AREKASLGKEAEELQALPALEELEEeELEELLAALGLPPDLSPEELLELLDRIEELQELLREAEELEEElQLEELEQEIA 373

                          330       340       350       360       370       380       390
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 1804876928  717 ELIQKKKLEDEA--IRKAKQGKEnlwRESLRKEEEEKQKRLQ--------------EEKTQEKVQEEERKVEEKQ 775
Cdd:COG4717    374 ALLAEAGVEDEEelRAALEQAEE---YQELKEELEELEEQLEellgeleellealdEEELEEELEELEEELEELE 445

Fourth Src homology 3 domain (or SH3D) of Intersectin; Intersectins (ITSNs) are adaptor proteins that function in exo- and endocytosis, actin cytoskeletal reorganization, and signal transduction. They are essential for initiating clathrin-coated pit formation. They bind to many proteins through their multidomain structure and facilitate the assembly of multimeric complexes. Vertebrates contain two ITSN proteins, ITSN1 and ITSN2, which exist in alternatively spliced short and long isoforms. The short isoforms contain two Eps15 homology domains (EH1 and EH2), a coiled-coil region and five SH3 domains (SH3A-E), while the long isoforms, in addition, contain RhoGEF (also called Dbl-homologous or DH), Pleckstrin homology (PH) and C2 domains. ITSN1 and ITSN2 are both widely expressed, with variations depending on tissue type and stage of development. The fourth SH3 domain (or SH3D) of ITSN1 has been shown to bind SHIP2, Numb, CdGAP, and N-WASP. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212773 [Multi-domain] Cd Length: 58 Bit Score: 56.58 E-value: 5.44e-10

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....*...
gi 1804876928 1152 QVIAmyDYVANNEDELNFSKGQLINVLNKDDPDWWQGEING-----VTGLFPSNYVKM 1204
Cdd:cd11839      3 QVIA--PFTATAENQLSLAVGQLVLVRKKSPSGWWEGELQArgkkrQIGWFPANYVKL 58

Domain of unknown function (DUF4670); This family of proteins is found in eukaryotes. Proteins in this family are typically between 373 and 763 amino acids in length.

Pssm-ID: 464815 [Multi-domain] Cd Length: 522 Bit Score: 64.20 E-value: 5.49e-10

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1804876928  372 QIDSINGTLPSYQKIQEEEPQKKLPVTFEdKRKANYERGNVELEKRRQALMEQQQREAE--RKAQKEKEEWERKQRELQE 449
Cdd:pfam15709  301 QTFVVTGNMESEEERSEEDPSKALLEKRE-QEKASRDRLRAERAEMRRLEVERKRREQEeqRRLQQEQLERAEKMREELE 379

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1804876928  450 QEWKKQLElEKRLEKQREL-ERQREEERRKEIERREAAKQELERQRRLEWERiRRQELlnQRNREQEEIVRLNSKKKSLH 528
Cdd:pfam15709  380 LEQQRRFE-EIRLRKQRLEeERQRQEEEERKQRLQLQAAQERARQQQEEFRR-KLQEL--QRKKQQEEAERAEAEKQRQK 455

                          170       180       190       200       210
                   ....*....|....*....|....*....|....*....|....*....|.
gi 1804876928  529 LELEALNGKHQQISGRLQDVRLRKQTQKTEIEvldKQCDLEIMEIKQLQQE 579
Cdd:pfam15709  456 ELEMQLAEEQKRLMEMAEEERLEYQRQKQEAE---EKARLEAEERRQKEEE 503

Family of unknown function (DUF5401); This is a family of unknown function found in Chromadorea.

Pssm-ID: 375164 [Multi-domain] Cd Length: 722 Bit Score: 64.37 E-value: 5.56e-10

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1804876928  487 KQELERQRRLEWERIRRQEllNQRNREQEEIVRLNSKKKSLHLELE---ALNGKHQQIS-GRLQDV-RLRKQTQKTEIE- 560
Cdd:pfam17380  287 RQQQEKFEKMEQERLRQEK--EEKAREVERRRKLEEAEKARQAEMDrqaAIYAEQERMAmERERELeRIRQEERKRELEr 364

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1804876928  561 VLDKQCDLEIMEIKQLQQelqdyqnkliyLVPEKQLLNERIKNMqlgntpdlgIDLLHKKSLEKEELCQRLKEQLDALEK 640
Cdd:pfam17380  365 IRQEEIAMEISRMRELER-----------LQMERQQKNERVRQE---------LEAARKVKILEEERQRKIQQQKVEMEQ 424

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1804876928  641 etasklsemdsfnnqlkcgnmddsvLQCLLSLLSCLNNLFLLLKELRESYNTQQLALEQLHKIKRDKLKEIERKRseliq 720
Cdd:pfam17380  425 -------------------------IRAEQEEARQREVRRLEEERAREMERVRLEEQERQQQVERLRQQEEERKR----- 474

                          250       260       270       280       290       300       310
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 1804876928  721 kKKLEDEAIRKAKQGKENLWRESLRKEEEEKQKRLQEEKTQEKVQEEErkVEEKQcepasalvnyKALYRFEARSHDE 798
Cdd:pfam17380  475 -KKLELEKEKRDRKRAEEQRRKILEKELEERKQAMIEEERKRKLLEKE--MEERQ----------KAIYEEERRREAE 539

chromosome segregation protein SMC, common bacterial type; SMC (structural maintenance of chromosomes) proteins bind DNA and act in organizing and segregating chromosomes for partition. SMC proteins are found in bacteria, archaea, and eukaryotes. This family represents the SMC protein of most bacteria. The smc gene is often associated with scpB (TIGR00281) and scpA genes, where scp stands for segregation and condensation protein. SMC was shown (in Caulobacter crescentus) to be induced early in S phase but present and bound to DNA throughout the cell cycle. [Cellular processes, Cell division, DNA metabolism, Chromosome-associated proteins]

Pssm-ID: 274008 [Multi-domain] Cd Length: 1179 Bit Score: 64.69 E-value: 5.67e-10

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1804876928  385 KIQEEEPQKKLpvtfeDKRKANYERGNV---ELEKRRQALmeQQQREAERKAQKEKEEWERKQRELQEQEWKkqlELEKR 461
Cdd:TIGR02168  171 KERRKETERKL-----ERTRENLDRLEDilnELERQLKSL--ERQAEKAERYKELKAELRELELALLVLRLE---ELREE 240

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1804876928  462 LEKQRELERQREEERRKEIERREAAKQEL--------ERQRRLEWERIRRQELLNQRNREQEEIVRLNSKKKSLHLELEA 533
Cdd:TIGR02168  241 LEELQEELKEAEEELEELTAELQELEEKLeelrlevsELEEEIEELQKELYALANEISRLEQQKQILRERLANLERQLEE 320

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1804876928  534 LNGKHQQISGRLQDVRLRKQTQKTEIEVLDKQCDLEIMEIKQLQQELQDYQNKLIYLvpEKQLLNERiknmqlgntpDLG 613
Cdd:TIGR02168  321 LEAQLEELESKLDELAEELAELEEKLEELKEELESLEAELEELEAELEELESRLEEL--EEQLETLR----------SKV 388

                          250       260       270       280       290       300       310       320
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1804876928  614 IDLLHKKSLEKEELcQRLKEQLDALEKETASKLSEMDSFNNQLKCGNMddsvlqcllsllsclnnlflllKELRESYNTQ 693
Cdd:TIGR02168  389 AQLELQIASLNNEI-ERLEARLERLEDRRERLQQEIEELLKKLEEAEL----------------------KELQAELEEL 445

                          330       340       350       360       370       380       390
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 1804876928  694 QLALEQLHKIKRDKLKEIERKRSELIQKKKLEDEAIRKAKQGKENLwrESLRKEEEEKQKRLQEEKTQEKVQEE 767
Cdd:TIGR02168  446 EEELEELQEELERLEEALEELREELEEAEQALDAAERELAQLQARL--DSLERLQENLEGFSEGVKALLKNQSG 517

Src homology 3 domain of Myosins Ie, If, and similar proteins; Myosins Ie (MyoIe) and If (MyoIf) are nonmuscle, unconventional, long tailed, class I myosins containing an N-terminal motor domain and a myosin tail with TH1, TH2, and SH3 domains. MyoIe interacts with the endocytic proteins, dynamin and synaptojanin-1, through its SH3 domain; it may play a role in clathrin-dependent endocytosis. In the kidney, MyoIe is critical for podocyte function and normal glomerular filtration. Mutations in MyoIe is associated with focal segmental glomerulosclerosis, a disease characterized by massive proteinuria and progression to end-stage kidney disease. MyoIf is predominantly expressed in the immune system; it plays a role in immune cell motility and innate immunity. Mutations in MyoIf may be associated with the loss of hearing. The MyoIf gene has also been found to be fused to the MLL (Mixed lineage leukemia) gene in infant acute myeloid leukemias (AML). SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212761 [Multi-domain] Cd Length: 53 Bit Score: 56.27 E-value: 6.02e-10

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|...
gi 1804876928  786 KALYRFEARSHDEMSFNSGDIIQVDEKTIGepGWLYGSFQGNFGWFPCNYVEK 838
Cdd:cd11827      3 KALYAYDAQDTDELSFNEGDIIEILKEDPS--GWWTGRLRGKEGLFPGNYVEK 53

Src homology 3 domain of Nitric Oxide Synthase TRaffic INducer; Nostrin is expressed in endothelial and epithelial cells and is involved in the regulation, trafficking and targeting of endothelial NOS (eNOS). It facilitates the endocytosis of eNOS by coordinating the functions of dynamin and the Wiskott-Aldrich syndrome protein (WASP). Increased expression of Nostrin may be correlated to preeclampsia. Nostrin contains an N-terminal F-BAR domain and a C-terminal SH3 domain. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212757 [Multi-domain] Cd Length: 53 Bit Score: 56.20 E-value: 6.08e-10

                           10        20        30        40
                   ....*....|....*....|....*....|....*....|....*...
gi 1804876928  926 ALCSWTAKKDNHLNFSKHDIITVLEQQEN-WWFGEVHGGRGWFPKSYV 972
Cdd:cd11823      4 ALYSYTANREDELSLQPGDIIEVHEKQDDgWWLGELNGKKGIFPATYV 51

First Src Homology 3 domain of Sorbin and SH3 domain containing (Sorbs) proteins and similar domains; This family, also called the vinexin family, is composed predominantly of adaptor proteins containing one sorbin homology (SoHo) and three SH3 domains. Members include the first SH3 domains of Sorbs1 (or ponsin), Sorbs2 (or ArgBP2), Vinexin (or Sorbs3), and similar domains. They are involved in the regulation of cytoskeletal organization, cell adhesion, and growth factor signaling. Members of this family bind multiple partners including signaling molecules like c-Abl, c-Arg, Sos, and c-Cbl, as well as cytoskeletal molecules such as vinculin and afadin. They may have overlapping functions. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212715 [Multi-domain] Cd Length: 53 Bit Score: 56.19 E-value: 6.16e-10

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|.
gi 1804876928 1154 IAMYDYVANNEDELNFSKGQLINVLNKDDPDWWQGEINGVTGLFPSNYVKM 1204
Cdd:cd11781      3 RALYPFKAQSAKELSLKKGDIIYIRRQIDKNWYEGEHNGRVGIFPASYVEI 53

Src Homology 3 domain of beta-Pak Interactive eXchange factor; Beta-PIX, also called Rho guanine nucleotide exchange factor 7 (ARHGEF7) or Cool (Cloned out of Library)-1, activates small GTPases by exchanging bound GDP for free GTP. It acts as a GEF for both Cdc42 and Rac 1, and plays important roles in regulating neuroendocrine exocytosis, focal adhesion maturation, cell migration, synaptic vesicle localization, and insulin secretion. PIX proteins contain an N-terminal SH3 domain followed by RhoGEF (also called Dbl-homologous or DH) and Pleckstrin Homology (PH) domains, and a C-terminal leucine-zipper domain for dimerization. The SH3 domain of PIX binds to an atypical PxxxPR motif in p21-activated kinases (PAKs) with high affinity. The binding of PAKs to PIX facilitate the localization of PAKs to focal complexes and also localizes PAKs to PIX targets Cdc43 and Rac, leading to the activation of PAKs. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212994 [Multi-domain] Cd Length: 54 Bit Score: 56.23 E-value: 6.97e-10

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....
gi 1804876928  786 KALYRFEARSHDEMSFNSGDIIQVDEKTIGepGWLYGSFQGNFGWFPCNYVEKM 839
Cdd:cd12061      3 RAKFNFQQTNEDELSFSKGDVIHVTRVEEG--GWWEGTHNGRTGWFPSNYVREI 54

Third Src homology 3 domain of ADAM-binding protein Eve-1; Eve-1, also called SH3 domain-containing protein 19 (SH3D19) or EEN-binding protein (EBP), exists in multiple alternatively spliced isoforms. The longest isoform contains five SH3 domain in the C-terminal region and seven proline-rich motifs in the N-terminal region. It is abundantly expressed in skeletal muscle and heart, and may be involved in regulating the activity of ADAMs (A disintegrin and metalloproteases). Eve-1 interacts with EEN, an endophilin involved in endocytosis and may be the target of the MLL-EEN fusion protein that is implicated in leukemogenesis. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212750 [Multi-domain] Cd Length: 51 Bit Score: 55.88 E-value: 7.79e-10

                           10        20        30        40
                   ....*....|....*....|....*....|....*....|....*....
gi 1804876928 1154 IAMYDYVANNEDELNFSKGQLINVLNKDDPDWWQGEINGVTGLFPSNYV 1202
Cdd:cd11816      3 VARFDFEGEQEDELSFSEGDVITLKEYVGEEWAKGELNGKIGIFPLNFV 51

First Src Homology 3 domain of SH3 domain containing ring finger 2; SH3RF2 is also called POSHER (POSH-eliminating RING protein) or HEPP1 (heart protein phosphatase 1-binding protein). It acts as an anti-apoptotic regulator of the JNK pathway by binding to and promoting the degradation of SH3RF1 (or POSH), a scaffold protein that is required for pro-apoptotic JNK activation. It may also play a role in cardiac functions together with protein phosphatase 1. SH3RF2 contains an N-terminal RING finger domain and three SH3 domains. This model represents the first SH3 domain, located at the N-terminal half, of SH3RF2. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212862 Cd Length: 54 Bit Score: 56.10 E-value: 8.17e-10

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|
gi 1804876928 1155 AMYDYVANNEDELNFSKGQLINVLNKDDPDWWQGEINGVTGLFPSNYVKM 1204
Cdd:cd11929      5 ALCNYRGHNPGDLKFNKGDVILLRRQLDENWYLGEINGVSGIFPASSVEV 54

First C-terminal Src homology 3 domain of Fungal Actin-binding protein 1; Abp1 is an adaptor protein that functions in receptor-mediated endocytosis and vesicle trafficking. It contains an N-terminal actin-binding module, the actin-depolymerizing factor (ADF) homology domain, a central proline-rich region, and a C-terminal SH3 domain (many yeast Abp1 proteins contain two C-terminal SH3 domains). Yeast Abp1 also contains two acidic domains that bind directly to the Arp2/3 complex, which is required to initiate actin polymerization. The SH3 domain of yeast Abp1 binds and localizes the kinases, Ark1p and Prk1p, which facilitate actin patch disassembly following vesicle internalization. It also mediates the localization to the actin patch of the synaptojanin-like protein, Sjl2p, which plays a key role in endocytosis. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212895 [Multi-domain] Cd Length: 54 Bit Score: 55.96 E-value: 8.59e-10

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|..
gi 1804876928 1154 IAMYDYVANNEDELNFSKGQLINVLNKDDPDWWQGE-INGVTGLFPSNYVKM 1204
Cdd:cd11962      3 VVLYDYEKDEDNEIELVEGEIVTNIEMVDEDWWMGTnSKGESGLFPSNYVEL 54

C-terminal (or second) Src homology 3 domain of VAV1 protein; VAV1 is expressed predominantly in the hematopoietic system and it plays an important role in the development and activation of B and T cells. It is activated by tyrosine phosphorylation to function as a guanine nucleotide exchange factor (GEF) for Rho GTPases following cell surface receptor activation, triggering various effects such as cytoskeletal reorganization, transcription regulation, cell cycle progression, and calcium mobilization. It also serves as a scaffold protein and has been shown to interact with Ku70, Socs1, Janus kinase 2, SIAH2, S100B, Abl gene, ZAP-70, SLP76, and Syk, among others. VAV proteins contain several domains that enable their function: N-terminal calponin homology (CH), acidic, RhoGEF (also called Dbl-homologous or DH), Pleckstrin Homology (PH), C1 (zinc finger), SH2, and two SH3 domains. The C-terminal SH3 domain of Vav1 interacts with a wide variety of proteins including cytoskeletal regulators (zyxin), RNA-binding proteins (Sam68), transcriptional regulators, viral proteins, and dynamin 2. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212909 [Multi-domain] Cd Length: 54 Bit Score: 55.72 E-value: 9.16e-10

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|...
gi 1804876928  786 KALYRFEARSHDEMSFNSGDIIQVDEKTiGEPGWLYGSFQGNFGWFPCNYVEK 838
Cdd:cd11976      3 KARYDFCARDRSELSLKEGDIIKILNKK-GQQGWWRGEIYGRVGWFPANYVEE 54

C-terminal (or second) Src homology 3 domain of VAV proteins; VAV proteins function both as cytoplasmic guanine nucleotide exchange factors (GEFs) for Rho GTPases and scaffold proteins and they play important roles in cell signaling by coupling cell surface receptors to various effector functions. They play key roles in processes that require cytoskeletal reorganization including immune synapse formation, phagocytosis, cell spreading, and platelet aggregation, among others. Vertebrates have three VAV proteins (VAV1, VAV2, and VAV3). VAV proteins contain several domains that enable their function: N-terminal calponin homology (CH), acidic, RhoGEF (also called Dbl-homologous or DH), Pleckstrin Homology (PH), C1 (zinc finger), SH2, and two SH3 domains. The SH3 domain of VAV is involved in the localization of proteins to specific sites within the cell, by interacting with proline-rich sequences within target proteins. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212764 [Multi-domain] Cd Length: 54 Bit Score: 55.71 E-value: 9.95e-10

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|...
gi 1804876928  786 KALYRFEARSHDEMSFNSGDIIQVDEKtIGEPGWLYGSFQGNFGWFPCNYVEK 838
Cdd:cd11830      3 KARYDFCARDMRELSLKEGDVVKIYNK-KGQQGWWRGEINGRIGWFPSTYVEE 54

Src homology 3 domain of Endophilin-A; Endophilins play roles in synaptic vesicle formation, virus budding, mitochondrial morphology maintenance, receptor-mediated endocytosis inhibition, and endosomal sorting. They are classified into two types, A and B. Vertebrates contain three endophilin-A isoforms (A1, A2, and A3). Endophilin-A proteins are enriched in the brain and play multiple roles in receptor-mediated endocytosis. They tubulate membranes and regulate calcium influx into neurons to trigger the activation of the endocytic machinery. They are also involved in the sorting of plasma membrane proteins, actin filament assembly, and the uncoating of clathrin-coated vesicles for fusion with endosomes. Endophilins contain an N-terminal N-BAR domain (BAR domain with an additional N-terminal amphipathic helix), followed by a variable region containing proline clusters, and a C-terminal SH3 domain. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212737 [Multi-domain] Cd Length: 55 Bit Score: 55.34 E-value: 1.21e-09

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....*..
gi 1804876928  785 YKALYRFEARSHDEMSFNSGDII----QVDEKtigepgWLYGSFQGNFGWFPCNYVE 837
Cdd:cd11803      3 CRALYDFEPENEGELGFKEGDIItltnQIDEN------WYEGMVNGQSGFFPVNYVE 53

Src Homology 3 domain of SH3 domain-containing protein 21 (SH3D21) and similar proteins; N-terminal SH3 domain of the uncharacterized protein SH3 domain-containing protein 21, and similar uncharacterized domains, it belongs to the CD2AP-like_3 subfamily of proteins. The CD2AP-like_3 subfamily is composed of the third SH3 domain (SH3C) of CD2AP, CIN85 (Cbl-interacting protein of 85 kDa), and similar domains. CD2AP and CIN85 are adaptor proteins that bind to protein partners and assemble complexes that have been implicated in T cell activation, kidney function, and apoptosis of neuronal cells. They also associate with endocytic proteins, actin cytoskeleton components, and other adaptor proteins involved in receptor tyrosine kinase (RTK) signaling. CD2AP and the main isoform of CIN85 contain three SH3 domains, a proline-rich region, and a C-terminal coiled-coil domain. All of these domains enable CD2AP and CIN85 to bind various protein partners and assemble complexes that have been implicated in many different functions. SH3C of both proteins have been shown to bind to ubiquitin. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 213018 [Multi-domain] Cd Length: 55 Bit Score: 55.55 E-value: 1.21e-09

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|...
gi 1804876928  785 YKALYRFEARSHDEMSFNSGDIIQVDEKTIGEPGWLYGSFQGNFGWFPCNYVE 837
Cdd:cd12142      2 CRVLFDYNPVAPDELALKKGDVIEVISKETEDEGWWEGELNGRRGFFPDNFVM 54

Fourth Src homology 3 domain of ADAM-binding protein Eve-1; Eve-1, also called SH3 domain-containing protein 19 (SH3D19) or EEN-binding protein (EBP), exists in multiple alternatively spliced isoforms. The longest isoform contains five SH3 domain in the C-terminal region and seven proline-rich motifs in the N-terminal region. It is abundantly expressed in skeletal muscle and heart, and may be involved in regulating the activity of ADAMs (A disintegrin and metalloproteases). Eve-1 interacts with EEN, an endophilin involved in endocytosis and may be the target of the MLL-EEN fusion protein that is implicated in leukemogenesis. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212751 [Multi-domain] Cd Length: 50 Bit Score: 55.18 E-value: 1.42e-09

                           10        20        30        40
                   ....*....|....*....|....*....|....*....|....*...
gi 1804876928 1008 IALYSYSSVEPGDLTFIEGEEILVTQK-DGEWWTGSIGDRTGIFPSNY 1054
Cdd:cd11817      3 VALYDFTGETEEDLSFQRGDRILVTEHlDAEWSRGRLNGREGIFPRAF 50

Src Homology 3 domain of Pak Interactive eXchange factors; PIX proteins are Rho guanine nucleotide exchange factors (GEFs), which activate small GTPases by exchanging bound GDP for free GTP. They act as GEFs for both Cdc42 and Rac 1, and have been implicated in cell motility, adhesion, neurite outgrowth, and cell polarity. Vertebrates contain two proteins from the PIX subfamily, alpha-PIX and beta-PIX. Alpha-PIX, also called ARHGEF6, is localized in dendritic spines where it regulates spine morphogenesis. Mutations in the ARHGEF6 gene cause X-linked intellectual disability in humans. Beta-PIX play roles in regulating neuroendocrine exocytosis, focal adhesion maturation, cell migration, synaptic vesicle localization, and insulin secretion. PIX proteins contain an N-terminal SH3 domain followed by RhoGEF (also called Dbl-homologous or DH) and Pleckstrin Homology (PH) domains, and a C-terminal leucine-zipper domain for dimerization. The SH3 domain of PIX binds to an atypical PxxxPR motif in p21-activated kinases (PAKs) with high affinity. The binding of PAKs to PIX facilitate the localization of PAKs to focal complexes and also localizes PAKs to PIX targets Cdc43 and Rac, leading to the activation of PAKs. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212810 [Multi-domain] Cd Length: 53 Bit Score: 55.40 E-value: 1.48e-09

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|
gi 1804876928 1009 ALYSYSSVEPGDLTFIEGEEILVTQK-DGEWWTGSIGDRTGIFPSNYVKP 1057
Cdd:cd11877      4 AKFNFEGTNEDELSFDKGDIITVTQVvEGGWWEGTLNGKTGWFPSNYVKE 53

Third Src Homology 3 domain (SH3C) of CD2-associated protein; CD2AP, also called CMS (Cas ligand with Multiple SH3 domains) or METS1 (Mesenchyme-to-Epithelium Transition protein with SH3 domains), is a cytosolic adaptor protein that plays a role in regulating the cytoskeleton. It is critical in cell-to-cell union necessary for kidney function. It also stabilizes the contact between a T cell and antigen-presenting cells. It is primarily expressed in podocytes at the cytoplasmic face of the slit diaphragm and serves as a linker anchoring podocin and nephrin to the actin cytoskeleton. CD2AP contains three SH3 domains, a proline-rich region, and a C-terminal coiled-coil domain. All of these domains enable CD2AP to bind various protein partners and assemble complexes that have been implicated in many different functions. This alignment model represents the third SH3 domain (SH3C) of CD2AP. SH3C has been shown to bind ubiquitin. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212989 [Multi-domain] Cd Length: 57 Bit Score: 55.22 E-value: 1.54e-09

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|.
gi 1804876928  786 KALYRFEARSHDEMSFNSGDIIQVDEKTIGEPGWLYGSFQGNFGWFPCNYV 836
Cdd:cd12056      5 KALFHYEGTNEDELDFKEGEIILIISKDTGEPGWWKGELNGKEGVFPDNFV 55

Second Src Homology 3 domain of Nck1 adaptor protein; Nck1 (also called Nckalpha) plays a crucial role in connecting signaling pathways of tyrosine kinase receptors and important effectors in actin dynamics and cytoskeletal remodeling. It binds and activates RasGAP, resulting in the downregulation of Ras. It is also involved in the signaling of endothilin-mediated inhibition of cell migration. Nck adaptor proteins regulate actin cytoskeleton dynamics by linking proline-rich effector molecules to protein tyrosine kinases and phosphorylated signaling intermediates. They contain three SH3 domains and a C-terminal SH2 domain. They function downstream of the PDGFbeta receptor and are involved in Rho GTPase signaling and actin dynamics. Vertebrates contain two Nck adaptor proteins: Nck1 (also called Nckalpha) and Nck2, which show partly overlapping functions but also bind distinct targets. The second SH3 domain of Nck appears to prefer ligands containing the APxxPxR motif. SH3 domains are protein interaction domains that usually bind to proline-rich ligands with moderate affinity and selectivity, preferentially a PxxP motif. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212834 [Multi-domain] Cd Length: 55 Bit Score: 55.43 E-value: 1.56e-09

                           10        20        30        40
                   ....*....|....*....|....*....|....*....|....*.
gi 1804876928 1157 YDYVANNEDELNFSKGQLINVLNKDDPDWWQGEINGVTGLFPSNYV 1202
Cdd:cd11901      8 FNYTAEREDELSLVKGTKVIVMEKCSDGWWRGSYNGQVGWFPSNYV 53

exonuclease SbcC; All proteins in this family for which functions are known are part of an exonuclease complex with sbcD homologs. This complex is involved in the initiation of recombination to regulate the levels of palindromic sequences in DNA. This family is based on the phylogenomic analysis of JA Eisen (1999, Ph.D. Thesis, Stanford University). [DNA metabolism, DNA replication, recombination, and repair]

Pssm-ID: 129705 [Multi-domain] Cd Length: 1042 Bit Score: 63.06 E-value: 1.60e-09

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1804876928  398 TFEDKRKAnyeRGNVELEKRRQALM-----EQQQREAERKAQKEKE--EWERKQRELQEQEWKKQLELEKrlekqreler 470
Cdd:TIGR00618  185 EFAKKKSL---HGKAELLTLRSQLLtlctpCMPDTYHERKQVLEKElkHLREALQQTQQSHAYLTQKREA---------- 251

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1804876928  471 qreeerrkeierreaAKQELERQRRLEWERIRRQELLNQRNREQEEIVRLNSKKKSLHLELEAlngKH-QQISGRLQDVR 549
Cdd:TIGR00618  252 ---------------QEEQLKKQQLLKQLRARIEELRAQEAVLEETQERINRARKAAPLAAHI---KAvTQIEQQAQRIH 313

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1804876928  550 LRKQTQKTEIEVldkqcdlEIMEIKQLQQELQDYQNKLIYLvpeKQLLNERIKNMQLGNTPDLGIDLLHKKSLEKEEL-- 627
Cdd:TIGR00618  314 TELQSKMRSRAK-------LLMKRAAHVKQQSSIEEQRRLL---QTLHSQEIHIRDAHEVATSIREISCQQHTLTQHIht 383

                          250       260       270       280       290       300       310       320
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1804876928  628 CQRLKEQLDALEKETASKLSEMDSFNNQLKCGNMDDSVLQCLlsllsclnnlfLLLKELRESYNTQQLALEQLHkikrdk 707
Cdd:TIGR00618  384 LQQQKTTLTQKLQSLCKELDILQREQATIDTRTSAFRDLQGQ-----------LAHAKKQQELQQRYAELCAAA------ 446

                          330       340       350       360       370       380       390
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 1804876928  708 lkeIERKRSELIQKKKLEDEAIRKAKQGKENLW-RESLRKEEEEKQKrlQEEKTQEKVQEEERKVEEKQCEPASALV 783
Cdd:TIGR00618  447 ---ITCTAQCEKLEKIHLQESAQSLKEREQQLQtKEQIHLQETRKKA--VVLARLLELQEEPCPLCGSCIHPNPARQ 518

Calcium binding and coiled-coil domain (CALCOCO1) like; Proteins found in this family are similar to the coiled-coil transcriptional coactivator protein coexpressed by Mus musculus (CoCoA/CALCOCO1). This protein binds to a highly conserved N-terminal domain of p160 coactivators, such as GRIP1, and thus enhances transcriptional activation by a number of nuclear receptors. CALCOCO1 has a central coiled-coil region with three leucine zipper motifs, which is required for its interaction with GRIP1 and may regulate the autonomous transcriptional activation activity of the C-terminal region.

Pssm-ID: 462303 [Multi-domain] Cd Length: 488 Bit Score: 62.22 E-value: 1.75e-09

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1804876928  408 ERGnvELEKRRQALMEQQQREAERKaQKEKEEWERKQRELQEQEWKKQLELEKRLEKQrELERQREEERRKEIERREAAK 487
Cdd:pfam07888   42 ERA--ELLQAQEAANRQREKEKERY-KRDREQWERQRRELESRVAELKEELRQSREKH-EELEEKYKELSASSEELSEEK 117

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1804876928  488 QELERQRRLEWERIRRQEllnqrnreqEEIVRLNSKKKSLHLELEALNGKHQQISGRLQDVRLRKQTQKTEIEVLDKqcd 567
Cdd:pfam07888  118 DALLAQRAAHEARIRELE---------EDIKTLTQRVLERETELERMKERAKKAGAQRKEEEAERKQLQAKLQQTEE--- 185

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1804876928  568 leimEIKQLQQELQDYQNKLIYLVPEKQLLNERIKNMQlgntpdLGIDLLHKKSLEKEELCQRLK---EQLDALEKETA- 643
Cdd:pfam07888  186 ----ELRSLSKEFQELRNSLAQRDTQVLQLQDTITTLT------QKLTTAHRKEAENEALLEELRslqERLNASERKVEg 255

                          250       260       270       280       290       300       310       320
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1804876928  644 --SKLSEMDSFNNQLKcGNMDDSVLQCLLSLLSCLNNLfLLLKELRESYNTQQLALEQLHKIKRDKLKEIER---KRSEL 718
Cdd:pfam07888  256 lgEELSSMAAQRDRTQ-AELHQARLQAAQLTLQLADAS-LALREGRARWAQERETLQQSAEADKDRIEKLSAelqRLEER 333

                          330       340       350       360       370
                   ....*....|....*....|....*....|....*....|....*....|....*....
gi 1804876928  719 IQKKKLEDEAIrKAKQGKEnlwRESLRKEEEEKQKRLQEEKTQEKV--QEEERKVEEKQ 775
Cdd:pfam07888  334 LQEERMEREKL-EVELGRE---KDCNRVQLSESRRELQELKASLRVaqKEKEQLQAEKQ 388

Src homology 3 domain of Signal Transducing Adaptor Molecule 1; STAM1 is part of the endosomal sorting complex required for transport (ESCRT-0) and is involved in sorting ubiquitinated cargo proteins from the endosome. It may also be involved in the regulation of IL2 and GM-CSF mediated signaling, and has been implicated in neural cell survival. STAMs were discovered as proteins that are highly phosphorylated following cytokine and growth factor stimulation. They function in cytokine signaling and surface receptor degradation, as well as regulate Golgi morphology. They associate with many proteins including Jak2 and Jak3 tyrosine kinases, Hrs, AMSH, and UBPY. STAM adaptor proteins contain VHS (Vps27, Hrs, STAM homology), ubiquitin interacting (UIM), and SH3 domains. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212897 [Multi-domain] Cd Length: 55 Bit Score: 54.95 E-value: 1.75e-09

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|.
gi 1804876928  923 KAQALCSWTAKKDNHLNFSKHDIITVLEQQE-NWWFGEVHGGRGWFPKSYV 972
Cdd:cd11964      2 KVRAIYDFEAAEDNELTFKAGDIITILDDSDpNWWKGETPQGTGLFPSNFV 52

C-terminal Src homology 3 domain of SH3 and cysteine-rich domain-containing protein 2 (Stac2); Stac proteins are putative adaptor proteins that contain a cysteine-rich C1 domain and one or two SH3 domains at the C-terminus. There are three mammalian members (Stac1, Stac2, and Stac3) of this family. Stac2 contains a single SH3 domain at the C-terminus unlike Stac1 and Stac3, which contain two C-terminal SH3 domains. Stac1 and Stac2 have been found to be expressed differently in mature dorsal root ganglia (DRG) neurons. Stac1 is mainly expressed in peptidergic neurons while Stac2 is found in a subset of nonpeptidergic and all trkB+ neurons. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212918 Cd Length: 53 Bit Score: 54.95 E-value: 1.87e-09

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|.
gi 1804876928 1007 YIALYSYSSVEPGDLTFIEGEEILVTQKDGE-WWTGSIGDRTGIFPSNYVK 1056
Cdd:cd11985      2 YVALYKFLPQENNDLPLQPGDRVMVVDDSNEdWWKGKSGDRVGFFPANFVQ 52

Src Homology 3 domain of fungal peroxisomal membrane protein Pex13p; Pex13p, located in the peroxisomal membrane, contains two transmembrane regions and a C-terminal SH3 domain. It binds to the peroxisomal targeting type I (PTS1) receptor Pex5p and the docking factor Pex14p through its SH3 domain. It is essential for both PTS1 and PTS2 protein import pathways into the peroxisomal matrix. Pex13p binds Pex14p, which contains a PxxP motif, in a classical fashion to the proline-rich ligand binding site of its SH3 domain. It binds the WxxxF/Y motif of Pex5p in a novel site that does not compete with Pex14p binding. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212705 [Multi-domain] Cd Length: 60 Bit Score: 54.97 E-value: 1.88e-09

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....*
gi 1804876928 1155 AMYDYV-ANNEDELNFSKGQLINVLNKDDP-----DWWQGEI-NGVTGLFPSNYV 1202
Cdd:cd11771      4 ALYDFTpENPEMELSLKKGDIVAVLSKTDPlgrdsEWWKGRTrDGRIGWFPSNYV 58

Second Src homology 3 domain of Rab3-interacting molecules (RIMs) binding proteins; RIMs binding proteins (RBPs, RIM-BPs) associate with calcium channels present in photoreceptors, neurons, and hair cells; they interact simultaneously with specific calcium channel subunits, and active zone proteins, RIM1 and RIM2. RIMs are part of the matrix at the presynaptic active zone and are associated with synaptic vesicles through their interaction with the small GTPase Rab3. RIM-BPs play a role in regulating synaptic transmission by serving as adaptors and linking calcium channels with the synaptic vesicle release machinery. RIM-BPs contain three SH3 domains and two to three fibronectin III repeats. Invertebrates contain one, while vertebrates contain at least two RIM-BPs, RIM-BP1 and RIM-BP2. RIM-BP1 is also called peripheral-type benzodiazapine receptor associated protein 1 (PRAX-1). Mammals contain a third protein, RIM-BP3. RIM-BP1 and RIM-BP2 are predominantly expressed in the brain where they display overlapping but distinct expression patterns, while RIM-BP3 is almost exclusively expressed in the testis and is essential in spermiogenesis. The SH3 domains of RIM-BPs bind to the PxxP motifs of RIM1, RIM2, and L-type (alpha1D) and N-type (alpha1B) calcium channel subunits. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212945 Cd Length: 62 Bit Score: 55.38 E-value: 1.89e-09

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....*....
gi 1804876928 1154 IAMYDYVANN--------EDELNFSKGQLINVLNKDDPD-WWQGEINGVTGLFPSNYVK 1203
Cdd:cd12012      3 VALFDYDPLTmspnpdaaEEELPFKEGQLIKVYGDKDADgFYLGEINGRRGLVPCNMVS 61

Third Src Homology 3 domain (SH3C) of CD2-associated protein and similar proteins; This subfamily is composed of the third SH3 domain (SH3C) of CD2AP, CIN85 (Cbl-interacting protein of 85 kDa), and similar domains. CD2AP and CIN85 are adaptor proteins that bind to protein partners and assemble complexes that have been implicated in T cell activation, kidney function, and apoptosis of neuronal cells. They also associate with endocytic proteins, actin cytoskeleton components, and other adaptor proteins involved in receptor tyrosine kinase (RTK) signaling. CD2AP and the main isoform of CIN85 contain three SH3 domains, a proline-rich region, and a C-terminal coiled-coil domain. All of these domains enable CD2AP and CIN85 to bind various protein partners and assemble complexes that have been implicated in many different functions. SH3C of both proteins have been shown to bind to ubiquitin. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212808 [Multi-domain] Cd Length: 55 Bit Score: 55.05 E-value: 1.98e-09

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|...
gi 1804876928  785 YKALYRFEARSHDEMSFNSGDIIQVDEKTIGEPGWLYGSFQGNFGWFPCNYVE 837
Cdd:cd11875      2 ARVLFDYEAENEDELTLREGDIVTILSKDCEDKGWWKGELNGKRGVFPDNFVE 54

Src homology 3 domain of ephexin-1-like SH3 domain containing Rho guanine nucleotide exchange factors; Members of this family contain RhoGEF (also called Dbl-homologous or DH), Pleckstrin Homology (PH), and C-terminal SH3 domains. They include the Rho guanine nucleotide exchange factors ARHGEF5, ARHGEF16, ARHGEF19, ARHGEF26, ARHGEF27 (also called ephexin-1), and similar proteins, and are also called ephexins because they interact directly with ephrin A receptors. GEFs interact with Rho GTPases via their DH domains to catalyze nucleotide exchange by stabilizing the nucleotide-free GTPase intermediate. They play important roles in neuronal development. The SH3 domains of ARHGEFs play an autoinhibitory role through intramolecular interactions with a proline-rich region N-terminal to the DH domain. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212727 [Multi-domain] Cd Length: 55 Bit Score: 55.03 E-value: 2.04e-09

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....*
gi 1804876928 1079 AQVTSAYVASGSEQLSLAPGQLILILKKNSSGWWQGElqaRGKKRQKGWFPASHV 1133
Cdd:cd11793      2 VQCVHAYTAQQPDELTLEEGDVVNVLRKMPDGWYEGE---RLRDGERGWFPSSYT 53

Src Homology 3 domain of Bbc1 and similar domains; This subfamily is composed of Saccharomyces cerevisiae Bbc1p, also called Mti1p (Myosin tail region-interacting protein), and similar proteins. Bbc1p interacts with and regulates type I myosins in yeast, Myo3p and Myo5p, which are involved in actin cytoskeletal reorganization. It also binds and inhibits Las17, a WASp family protein that functions as an activator of the Arp2/3 complex. Bbc1p contains an N-terminal SH3 domain. SH3 domains bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs; they play a role in the regulation of enzymes by intramolecular interactions, changing the subcellular localization of signal pathway components and mediate multiprotein complex assemblies.

Pssm-ID: 212820 [Multi-domain] Cd Length: 60 Bit Score: 55.04 E-value: 2.10e-09

                           10        20        30        40        50        60
                   ....*....|....*....|....*....|....*....|....*....|....*....|....
gi 1804876928 1000 AYTVgdeyIALYSYSSVEPGDLTFIEGEEILVTQK-DGEWWTG----SIGDR-TGIFPSNYVKP 1057
Cdd:cd11887      1 PFKV----KALYPYESDHEDDLNFDVGQLITVTEEeDADWYFGeyvdSNGNTkEGIFPKNFVEV 60

MAEBL; Provisional

Pssm-ID: 173412 [Multi-domain] Cd Length: 2084 Bit Score: 62.85 E-value: 2.15e-09

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1804876928  400 EDKRKANYERGNVELEKRRQALMEQQQREAE--RKAQKEKE-EWERKQRELQEQEWKKQLELEKRLEKQRELERQREEER 476
Cdd:PTZ00121  1173 EDAKKAEAARKAEEVRKAEELRKAEDARKAEaaRKAEEERKaEEARKAEDAKKAEAVKKAEEAKKDAEEAKKAEEERNNE 1252

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1804876928  477 RKEIERREAAKQELERQRRLEWERIRRQELLN--QRNREQEEIVRLNSKKKSLHLELEALNG-KHQQISGRLQDVRLRKQ 553
Cdd:PTZ00121  1253 EIRKFEEARMAHFARRQAAIKAEEARKADELKkaEEKKKADEAKKAEEKKKADEAKKKAEEAkKADEAKKKAEEAKKKAD 1332

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1804876928  554 TQKTEIEVLDKQCDLEIMEIKQLQQELQDYQNKliYLVPEKQLLNERIKNMQLGNTPD--LGIDLLHKKSLEKEELCQRL 631
Cdd:PTZ00121  1333 AAKKKAEEAKKAAEAAKAEAEAAADEAEAAEEK--AEAAEKKKEEAKKKADAAKKKAEekKKADEAKKKAEEDKKKADEL 1410

                          250       260       270       280       290       300       310       320
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1804876928  632 KEQLDALEK-ETASKLSEMDSFNNQLKcgnmddsvlqcllsllsclnnlflllKELRESYNTQQLA--LEQLHKIKRDKL 708
Cdd:PTZ00121  1411 KKAAAAKKKaDEAKKKAEEKKKADEAK--------------------------KKAEEAKKADEAKkkAEEAKKAEEAKK 1464

                          330       340       350       360       370       380       390
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|..
gi 1804876928  709 KEIERKRSELIQKKKLE----DEAIRKAKQGKENlwRESLRKEEEEKQKRLQEEKTQEKVQEEE-RKVEEKQ 775
Cdd:PTZ00121  1465 KAEEAKKADEAKKKAEEakkaDEAKKKAEEAKKK--ADEAKKAAEAKKKADEAKKAEEAKKADEaKKAEEAK 1534

Src homology 3 domain of eumetazoan Actin-binding protein 1; Abp1, also called drebrin-like protein, is an adaptor protein that functions in receptor-mediated endocytosis and vesicle trafficking. It contains an N-terminal actin-binding module, the actin-depolymerizing factor (ADF) homology domain, a helical domain, and a C-terminal SH3 domain. Mammalian Abp1, unlike yeast Abp1, does not contain an acidic domain that interacts with the Arp2/3 complex. It regulates actin dynamics indirectly by interacting with dynamin and WASP family proteins. Abp1 deficiency causes abnormal organ structure and function of the spleen, heart, and lung of mice. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212893 [Multi-domain] Cd Length: 54 Bit Score: 54.71 E-value: 2.21e-09

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|...
gi 1804876928 1153 VIAMYDYVANNEDELNFSKGQLINVLNKDDPDWWQG-EINGVTGLFPSNYVKM 1204
Cdd:cd11960      2 ARALYDYQAADDTEISFDPGDIITDIEQIDEGWWRGtGPDGTYGLFPANYVEL 54

Src homology 3 domain of Abl Interactor proteins; Abl interactor (Abi) proteins are adaptor proteins serving as binding partners and substrates of Abl tyrosine kinases. They are involved in regulating actin cytoskeletal reorganization and play important roles in membrane-ruffling, endocytosis, cell motility, and cell migration. They localize to sites of actin polymerization in epithelial adherens junction and immune synapses, as well as to the leading edge of lamellipodia. Vertebrates contain two Abi proteins, Abi1 and Abi2. Abi1 displays a wide expression pattern while Abi2 is highly expressed in the eye and brain. Abi proteins contain a homeobox homology domain, a proline-rich region, and a SH3 domain. The SH3 domain of Abi binds to a PxxP motif in Abl. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212760 [Multi-domain] Cd Length: 52 Bit Score: 54.63 E-value: 2.32e-09

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|..
gi 1804876928  786 KALYRFEARSHDEMSFNSGDIIQVDEKTigEPGWLYGSFQGNFGWFPCNYVE 837
Cdd:cd11826      3 VALYDYTADKDDELSFQEGDIIYVTKKN--DDGWYEGVLNGVTGLFPGNYVE 52

Second C-terminal Src homology 3 domain of Dynamin Binding Protein, also called Tuba, and similar domains; DNMBP or Tuba is a cdc42-specific guanine nucleotide exchange factor (GEF) that contains four N-terminal SH3 domains, a central RhoGEF [or Dbl homology (DH)] domain followed by a Bin/Amphiphysin/Rvs (BAR) domain, and two C-terminal SH3 domains. It provides a functional link between dynamin, Rho GTPase signaling, and actin dynamics. It plays an important role in regulating cell junction configuration. The C-terminal SH3 domains of DNMBP bind to N-WASP and Ena/VASP proteins, which are key regulatory proteins of the actin cytoskeleton. Also included in this subfamily is the second C-terminal SH3 domain of Rho guanine nucleotide exchange factor 37 (ARHGEF37), whose function is still unknown. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212734 [Multi-domain] Cd Length: 57 Bit Score: 54.69 E-value: 2.58e-09

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....
gi 1804876928 1152 QVIAMYDYVANNEDELNFSKGQLINVLNKDD----PDWWQGEINGVTGLFPSNY 1201
Cdd:cd11800      1 YYYALYTFEARSPGELSVTEGQVVTVLEKHDlkgnPEWWLVEDRGKQGYVPSNY 54

First C-terminal Src homology 3 domain of SH3 and cysteine-rich domain-containing protein 3 (Stac3); Stac proteins are putative adaptor proteins that contain a cysteine-rich C1 domain and one or two SH3 domains at the C-terminus. There are three mammalian members (Stac1, Stac2, and Stac3) of this family. Stac1 and Stac3 contain two SH3 domains while Stac2 contains a single SH3 domain at the C-terminus. Stac1 and Stac2 have been found to be expressed differently in mature dorsal root ganglia (DRG) neurons. Stac1 is mainly expressed in peptidergic neurons while Stac2 is found in a subset of nonpeptidergic and all trkB+ neurons. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212919 [Multi-domain] Cd Length: 53 Bit Score: 54.53 E-value: 2.63e-09

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|
gi 1804876928 1007 YIALYSYSSVEPGDLTFIEGEEILVTQ-KDGEWWTGSIGDRTGIFPSNYV 1055
Cdd:cd11986      2 FVALYRFKALEKDDLDFHPGERITVIDdSNEEWWRGKIGEKTGYFPMNFI 51

C-terminal (or second) Src homology 3 domain of VAV1 protein; VAV1 is expressed predominantly in the hematopoietic system and it plays an important role in the development and activation of B and T cells. It is activated by tyrosine phosphorylation to function as a guanine nucleotide exchange factor (GEF) for Rho GTPases following cell surface receptor activation, triggering various effects such as cytoskeletal reorganization, transcription regulation, cell cycle progression, and calcium mobilization. It also serves as a scaffold protein and has been shown to interact with Ku70, Socs1, Janus kinase 2, SIAH2, S100B, Abl gene, ZAP-70, SLP76, and Syk, among others. VAV proteins contain several domains that enable their function: N-terminal calponin homology (CH), acidic, RhoGEF (also called Dbl-homologous or DH), Pleckstrin Homology (PH), C1 (zinc finger), SH2, and two SH3 domains. The C-terminal SH3 domain of Vav1 interacts with a wide variety of proteins including cytoskeletal regulators (zyxin), RNA-binding proteins (Sam68), transcriptional regulators, viral proteins, and dynamin 2. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212909 [Multi-domain] Cd Length: 54 Bit Score: 54.56 E-value: 2.91e-09

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|
gi 1804876928 1155 AMYDYVANNEDELNFSKGQLINVLNKDDPD-WWQGEINGVTGLFPSNYVK 1203
Cdd:cd11976      4 ARYDFCARDRSELSLKEGDIIKILNKKGQQgWWRGEIYGRVGWFPANYVE 53

Src homology 3 domain of Signal Transducing Adaptor Molecules; STAMs were discovered as proteins that are highly phosphorylated following cytokine and growth factor stimulation. They function in cytokine signaling and surface receptor degradation, as well as regulate Golgi morphology. They associate with many proteins including Jak2 and Jak3 tyrosine kinases, Hrs, AMSH, and UBPY. STAM adaptor proteins contain VHS (Vps27, Hrs, STAM homology), ubiquitin interacting (UIM), and SH3 domains. There are two vertebrate STAMs, STAM1 and STAM2, which may be functionally redundant; vertebrate STAMs contain ITAM motifs. They are part of the endosomal sorting complex required for transport (ESCRT-0). STAM2 deficiency in mice did not cause any obvious abnormality, while STAM1 deficiency resulted in growth retardation. Loss of both STAM1 and STAM2 in mice proved lethal, indicating that STAMs are important for embryonic development. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212754 [Multi-domain] Cd Length: 54 Bit Score: 54.39 E-value: 3.06e-09

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|...
gi 1804876928  923 KAQALCSWTAKKDNHLNFSKHDIITVLEQQ-ENWWFGEVHGGRGWFPKSYVKI 974
Cdd:cd11820      2 KVRALYDFEAAEDNELTFKAGEIITVLDDSdPNWWKGSNHRGEGLFPANFVTA 54

First Src Homology 3 domain of SH3 domain containing ring finger proteins; This model represents the first SH3 domain of SH3RF1 (or POSH), SH3RF2 (or POSHER), SH3RF3 (POSH2), and similar domains. Members of this family are scaffold proteins that function as E3 ubiquitin-protein ligases. They all contain an N-terminal RING finger domain and multiple SH3 domains; SH3RF1 and SH3RF3 have four SH3 domains while SH3RF2 has three. SH3RF1 plays a role in calcium homeostasis through the control of the ubiquitin domain protein Herp. It may also have a role in regulating death receptor mediated and JNK mediated apoptosis. SH3RF3 interacts with p21-activated kinase 2 (PAK2) and GTP-loaded Rac1. It may play a role in regulating JNK mediated apoptosis in certain conditions. SH3RF2 acts as an anti-apoptotic regulator of the JNK pathway by binding to and promoting the degradation of SH3RF1. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212720 [Multi-domain] Cd Length: 53 Bit Score: 54.29 E-value: 3.23e-09

                           10        20        30        40
                   ....*....|....*....|....*....|....*....|....*....
gi 1804876928 1009 ALYSYSSVEPGDLTFIEGEEILVTQK-DGEWWTGSIGDRTGIFPSNYVK 1056
Cdd:cd11786      4 ALYNYEGKEPGDLSFKKGDIILLRKRiDENWYHGECNGKQGFFPASYVQ 52

Src homology 3 domain of Apoptosis Stimulating of p53 proteins (ASPP); The ASPP family of proteins bind to important regulators of apoptosis (p53, Bcl-2, and RelA) and cell growth (APCL, PP1). They share similarity at their C-termini, where they harbor a proline-rich region, four ankyrin (ANK) repeats, and an SH3 domain. Vertebrates contain three members of the family: ASPP1, ASPP2, and iASPP. ASPP1 and ASPP2 activate the apoptotic function of the p53 family of tumor suppressors (p53, p63, and p73), while iASPP is an oncoprotein that specifically inhibits p53-induced apoptosis. The expression of ASPP proteins is altered in tumors; ASPP1 and ASPP2 are downregulated whereas iASPP is upregulated is some cancer types. ASPP proteins also bind and regulate protein phosphatase 1 (PP1), and this binding is competitive with p53 binding. The SH3 domain and the ANK repeats of ASPP contribute to the p53 binding site; they bind to the DNA binding domain of p53. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212741 [Multi-domain] Cd Length: 57 Bit Score: 54.31 E-value: 3.27e-09

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....*.
gi 1804876928 1152 QVIAMYDYVANNEDELNFSKGQLINVLNKDDPD---WWQGEINGVTGLFPSNYVKM 1204
Cdd:cd11807      2 VVYALFDYEAENGDELSFREGDELTVLRKGDDDeteWWWARLNDKEGYVPRNLLGL 57

Second Src Homology 3 domain of Nck2 adaptor protein; Nck2 (also called Nckbeta or Growth factor receptor-bound protein 4, Grb4) plays a crucial role in connecting signaling pathways of tyrosine kinase receptors and important effectors in actin dynamics and cytoskeletal remodeling. It binds neuronal signaling proteins such as ephrinB and Disabled-1 (Dab-1) exclusively. Nck adaptor proteins regulate actin cytoskeleton dynamics by linking proline-rich effector molecules to protein tyrosine kinases and phosphorylated signaling intermediates. They contain three SH3 domains and a C-terminal SH2 domain. They function downstream of the PDGFbeta receptor and are involved in Rho GTPase signaling and actin dynamics. Vertebrates contain two Nck adaptor proteins: Nck1 (also called Nckalpha) and Nck2, which show partly overlapping functions but also bind distinct targets. The second SH3 domain of Nck appears to prefer ligands containing the APxxPxR motif. SH3 domains are protein interaction domains that usually bind to proline-rich ligands with moderate affinity and selectivity, preferentially a PxxP motif. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212835 [Multi-domain] Cd Length: 55 Bit Score: 54.24 E-value: 3.31e-09

                           10        20        30        40
                   ....*....|....*....|....*....|....*....|....*.
gi 1804876928 1157 YDYVANNEDELNFSKGQLINVLNKDDPDWWQGEINGVTGLFPSNYV 1202
Cdd:cd11902      7 FAYVAEREDELSLVKGSRVTVMEKCSDGWWRGSYNGQIGWFPSNYV 52

C-terminal Src homology 3 domain of Growth factor receptor-bound protein 2; GRB2 is a critical signaling molecule that regulates the Ras pathway by linking tyrosine kinases to the Ras guanine nucleotide releasing protein Sos (son of sevenless), which converts Ras to the active GTP-bound state. It is ubiquitously expressed in all tissues throughout development and is important in cell cycle progression, motility, morphogenesis, and angiogenesis. In lymphocytes, GRB2 is associated with antigen receptor signaling components. GRB2 contains an N-terminal SH3 domain, a central SH2 domain, and a C-terminal SH3 domain. The C-terminal SH3 domain of GRB2 binds to Gab2 (Grb2-associated binder 2) through epitopes containing RxxK motifs, as well as to the proline-rich C-terminus of FGRF2. SH3 domains are protein interaction domains that typically bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212882 [Multi-domain] Cd Length: 53 Bit Score: 54.07 E-value: 3.33e-09

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|.
gi 1804876928  924 AQALCSWTAKKDNHLNFSKHDIITVLEQQE-NWWFGEVHGGRGWFPKSYVK 973
Cdd:cd11949      2 VQALFDFDPQEDGELGFRRGDFIEVMDNSDpNWWKGACHGQTGMFPRNYVT 52

Fifth Src homology 3 domain (or SH3E) of Intersectin; Intersectins (ITSNs) are adaptor proteins that function in exo- and endocytosis, actin cytoskeletal reorganization, and signal transduction. They are essential for initiating clathrin-coated pit formation. They bind to many proteins through their multidomain structure and facilitate the assembly of multimeric complexes. Vertebrates contain two ITSN proteins, ITSN1 and ITSN2, which exist in alternatively spliced short and long isoforms. The short isoforms contain two Eps15 homology domains (EH1 and EH2), a coiled-coil region and five SH3 domains (SH3A-E), while the long isoforms, in addition, contain RhoGEF (also called Dbl-homologous or DH), Pleckstrin homology (PH) and C2 domains. ITSN1 and ITSN2 are both widely expressed, with variations depending on tissue type and stage of development. The fifth SH3 domain (or SH3E) of ITSN1 has been shown to bind many protein partners including SGIP1, Sos1, dynamin1/2, CIN85, c-Cbl, SHIP2, N-WASP, and synaptojanin-1, among others. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212774 [Multi-domain] Cd Length: 53 Bit Score: 54.34 E-value: 3.43e-09

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|.
gi 1804876928  787 ALYRFEARSHDEMSFNSGDIIQVDEKTigEPGWLYGSFQGNFGWFPCNYVE 837
Cdd:cd11840      4 ALFPYTAQNEDELSFQKGDIINVLSKD--DPDWWRGELNGQTGLFPSNYVE 52

Src Homology 3 domain of Small G protein Signaling Modulator 3; SGSM3 is also called Merlin-associated protein (MAP), RUN and SH3 domain-containing protein (RUSC3), RUN and TBC1 domain-containing protein 3 (RUTBC3), Rab GTPase-activating protein 5 (RabGAP5), or Rab GAP-like protein (RabGAPLP). It is expressed ubiquitously and functions as a regulator of small G protein RAP- and RAB-mediated neuronal signaling. It is involved in modulating NGF-mediated neurite outgrowth and differentiation. It also interacts with the tumor suppressor merlin and may play a role in the merlin-associated suppression of cell growth. SGSM3 contains TBC, SH3, and RUN domains. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212747 Cd Length: 53 Bit Score: 54.04 E-value: 3.44e-09

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|...
gi 1804876928  923 KAQALCSWTAKKDNHLNFSKHDIITVLEQQ-ENWWFGEVHGGRGWFPKSYVKI 974
Cdd:cd11813      1 RAKALLDFERHDDDELGFRKNDIITIISQKdEHCWVGELNGLRGWFPAKFVEL 53

C-terminal Src Homology 3 domain of Nebulette and LIM-nebulette (or Lasp2); Nebulette is a cardiac-specific protein that localizes to the Z-disc. It interacts with tropomyosin and is important in stabilizing actin thin filaments in cardiac muscles. Polymorphisms in the nebulette gene are associated with dilated cardiomyopathy, with some mutations resulting in severe heart failure. Nebulette is a 107kD protein that contains an N-terminal acidic region, multiple nebulin repeats, and a C-terminal SH3 domain. LIM-nebulette, also called Lasp2 (LIM and SH3 domain protein 2), is an alternatively spliced variant of nebulette. Although it shares a gene with nebulette, Lasp2 is not transcribed from a muscle-specific promoter, giving rise to its multiple tissue expression pattern with highest amounts in the brain. It can crosslink actin filaments and it affects cell spreading. Lasp2 is a 34kD protein containing an N-terminal LIM domain, three nebulin repeats, and a C-terminal SH3 domain. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212868 [Multi-domain] Cd Length: 58 Bit Score: 54.24 E-value: 3.62e-09

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....*
gi 1804876928  785 YKALYRFEARSHDEMSFNSGDIIqVDEKTIGEpGWLYGSFQ--GNFGWFPCNYVE 837
Cdd:cd11935      3 YRAMYDYSAQDEDEVSFRDGDYI-VNVQPIDE-GWMYGTVQrtGRTGMLPANYIE 55

Src Homology 3 domain of Sdc25/Cdc25 guanine nucleotide exchange factors; This subfamily is composed of the Saccharomyces cerevisiae guanine nucleotide exchange factors (GEFs) Sdc25 and Cdc25, and similar proteins. These GEFs regulate Ras by stimulating the GDP/GTP exchange on Ras. Cdc25 is involved in the Ras/PKA pathway that plays an important role in the regulation of metabolism, stress responses, and proliferation, depending on available nutrients and conditions. Proteins in this subfamily contain an N-terminal SH3 domain as well as REM (Ras exchanger motif) and RasGEF domains at the C-terminus. SH3 domains bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs; they play a role in the regulation of enzymes by intramolecular interactions, changing the subcellular localization of signal pathway components and mediate multiprotein complex assemblies.

Pssm-ID: 212816 Cd Length: 55 Bit Score: 54.21 E-value: 3.63e-09

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|...
gi 1804876928  925 QALCSWTAKKDNHLNFSKHDIITVLEQQEN-WWFGEVHGG-----RGWFPKSY 971
Cdd:cd11883      3 VALYDFTPKSKNQLSFKAGDIIYVLNKDPSgWWDGVIISSsgkvkRGWFPSNY 55

Src homology 3 domain of Yes Protein Tyrosine Kinase; Yes (or c-Yes) is a member of the Src subfamily of proteins, which are cytoplasmic (or non-receptor) PTKs. c-Yes kinase is the cellular homolog of the oncogenic protein (v-Yes) encoded by the Yamaguchi 73 and Esh sarcoma viruses. It displays functional overlap with other Src subfamily members, particularly Src. It also shows some unique functions such as binding to occludins, transmembrane proteins that regulate extracellular interactions in tight junctions. Yes also associates with a number of proteins in different cell types that Src does not interact with, like JAK2 and gp130 in pre-adipocytes, and Pyk2 in treated pulmonary vein endothelial cells. Although the biological function of Yes remains unclear, it appears to have a role in regulating cell-cell interactions and vesicle trafficking in polarized cells. Src kinases contain an N-terminal SH4 domain with a myristoylation site, followed by SH3 and SH2 domains, a tyr kinase domain, and a regulatory C-terminal region containing a conserved tyr. They are activated by autophosphorylation at the tyr kinase domain, but are negatively regulated by phosphorylation at the C-terminal tyr by Csk (C-terminal Src Kinase). The SH3 domain of Src kinases contributes to substrate recruitment by binding adaptor proteins/substrates, and regulation of kinase activity through an intramolecular interaction. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212940 [Multi-domain] Cd Length: 58 Bit Score: 54.27 E-value: 3.72e-09

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|.
gi 1804876928 1154 IAMYDYVANNEDELNFSKGQLINVLNKDDPDWWQGE--INGVTGLFPSNYV 1202
Cdd:cd12007      4 VALYDYEARTTEDLSFKKGERFQIINNTEGDWWEARsiATGKNGYIPSNYV 54

C-terminal Src homology 3 domain of Growth factor receptor-bound protein 2 (GRB2) and related proteins; This family includes the adaptor protein GRB2 and related proteins including Drosophila melanogaster Downstream of receptor kinase (DRK), Caenorhabditis elegans Sex muscle abnormal protein 5 (Sem-5), GRB2-related adaptor protein (GRAP), GRAP2, and similar proteins. Family members contain an N-terminal SH3 domain, a central SH2 domain, and a C-terminal SH3 domain. GRB2/Sem-5/DRK is a critical signaling molecule that regulates the Ras pathway by linking tyrosine kinases to the Ras guanine nucleotide releasing protein Sos (son of sevenless), which converts Ras to the active GTP-bound state. GRAP2 plays an important role in T cell receptor (TCR) signaling by promoting the formation of the SLP-76:LAT complex, which couples the TCR to the Ras pathway. GRAP acts as a negative regulator of T cell receptor (TCR)-induced lymphocyte proliferation by downregulating the signaling to the Ras/ERK pathway. The C-terminal SH3 domains (SH3c) of GRB2 and GRAP2 have been shown to bind to classical PxxP motif ligands, as well as to non-classical motifs. GRB2 SH3c binds Gab2 (Grb2-associated binder 2) through epitopes containing RxxK motifs, while the SH3c of GRAP2 binds to the phosphatase-like protein HD-PTP via a RxxxxK motif. SH3 domains are protein interaction domains that typically bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212739 [Multi-domain] Cd Length: 53 Bit Score: 54.17 E-value: 3.91e-09

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|..
gi 1804876928  923 KAQALCSWTAKKDNHLNFSKHDIITVLEQ-QENWWFGEVHGGRGWFPKSYVK 973
Cdd:cd11805      1 RVQALYDFNPQEPGELEFRRGDIITVLDSsDPDWWKGELRGRVGIFPANYVQ 52

First Src Homology 3 domain of Sorbin and SH3 domain containing (Sorbs) proteins and similar domains; This family, also called the vinexin family, is composed predominantly of adaptor proteins containing one sorbin homology (SoHo) and three SH3 domains. Members include the first SH3 domains of Sorbs1 (or ponsin), Sorbs2 (or ArgBP2), Vinexin (or Sorbs3), and similar domains. They are involved in the regulation of cytoskeletal organization, cell adhesion, and growth factor signaling. Members of this family bind multiple partners including signaling molecules like c-Abl, c-Arg, Sos, and c-Cbl, as well as cytoskeletal molecules such as vinculin and afadin. They may have overlapping functions. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212715 [Multi-domain] Cd Length: 53 Bit Score: 53.88 E-value: 3.91e-09

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....*.
gi 1804876928  786 KALYRFEARSHDEMSFNSGDII----QVDEKtigepgWLYGSFQGNFGWFPCNYVE 837
Cdd:cd11781      3 RALYPFKAQSAKELSLKKGDIIyirrQIDKN------WYEGEHNGRVGIFPASYVE 52

Src Homology 3 domain of alpha-Pak Interactive eXchange factor; Alpha-PIX, also called Rho guanine nucleotide exchange factor 6 (ARHGEF6) or Cool (Cloned out of Library)-2, activates small GTPases by exchanging bound GDP for free GTP. It acts as a GEF for both Cdc42 and Rac 1, and is localized in dendritic spines where it regulates spine morphogenesis. It controls dendritic length and spine density in the hippocampus. Mutations in the ARHGEF6 gene cause X-linked intellectual disability in humans. PIX proteins contain an N-terminal SH3 domain followed by RhoGEF (also called Dbl-homologous or DH) and Pleckstrin Homology (PH) domains, and a C-terminal leucine-zipper domain for dimerization. The SH3 domain of PIX binds to an atypical PxxxPR motif in p21-activated kinases (PAKs) with high affinity. The binding of PAKs to PIX facilitate the localization of PAKs to focal complexes and also localizes PAKs to PIX targets Cdc43 and Rac, leading to the activation of PAKs. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212993 Cd Length: 58 Bit Score: 54.24 E-value: 4.32e-09

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....*.
gi 1804876928  786 KALYRFEARSHDEMSFNSGDIIQVDEktIGEPGWLYGSFQGNFGWFPCNYVEKMPS 841
Cdd:cd12060      5 KARFNFKQTNEDELSVCKGDIIYVTR--VEEGGWWEGTLNGKTGWFPSNYVREIKS 58

C-terminal Src Homology 3 domain of LIM and SH3 domain protein 1; Lasp1 is a cytoplasmic protein that binds focal adhesion proteins and is involved in cell signaling, migration, and proliferation. It is overexpressed in several cancer cells including breast, ovarian, bladder, and liver. In cancer cells, it can be found in the nucleus; its degree of nuclear localization correlates with tumor size and poor prognosis. Lasp1 is a 36kD protein containing an N-terminal LIM domain, two nebulin repeats, and a C-terminal SH3 domain. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212867 [Multi-domain] Cd Length: 59 Bit Score: 54.23 E-value: 4.54e-09

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....*..
gi 1804876928  785 YKALYRFEARSHDEMSFNSGDIIqVDEKTIGEpGWLYGSFQ--GNFGWFPCNYVEKM 839
Cdd:cd11934      5 YRAVYDYNAADEDEVSFQDGDTI-VNVQQIDD-GWMYGTVErtGDTGMLPANYVEAI 59

Src Homology 3 domain of Tec-like Protein Tyrosine Kinases; The Tec (Tyrosine kinase expressed in hepatocellular carcinoma) subfamily is composed of Tec, Btk, Bmx (Etk), Itk (Tsk, Emt), Rlk (Txk), and similar proteins. They are cytoplasmic (or nonreceptor) tyr kinases containing Src homology protein interaction domains (SH3, SH2) N-terminal to the catalytic tyr kinase domain. Most Tec subfamily members (except Rlk) also contain an N-terminal pleckstrin homology (PH) domain, which binds the products of PI3K and allows membrane recruitment and activation. In addition, some members contain the Tec homology (TH) domain, which contains proline-rich and zinc-binding regions. Tec kinases are expressed mainly by haematopoietic cells, although Tec and Bmx are also found in endothelial cells. B-cells express Btk and Tec, while T-cells express Itk, Txk, and Tec. Collectively, Tec kinases are expressed in a variety of myeloid cells such as mast cells, platelets, macrophages, and dendritic cells. Each Tec kinase shows a distinct cell-type pattern of expression. The function of Tec kinases in lymphoid cells have been studied extensively. They play important roles in the development, differentiation, maturation, regulation, survival, and function of B-cells and T-cells. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212702 [Multi-domain] Cd Length: 54 Bit Score: 53.82 E-value: 4.55e-09

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|...
gi 1804876928 1152 QVIAMYDYVANNEDELNFSKGQLINVLNKDDPDWWQG-EINGVTGLFPSNYVK 1203
Cdd:cd11768      1 IVVALYDFQPIEPGDLPLEKGEEYVVLDDSNEHWWRArDKNGNEGYIPSNYVT 53

Family of unknown function (DUF5401); This is a family of unknown function found in Chromadorea.

Pssm-ID: 375164 [Multi-domain] Cd Length: 722 Bit Score: 61.29 E-value: 4.63e-09

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                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1804876928  415 EKRRQALMEQQQREAERKAQKEKEEWERKQRELQEQEWKKQLELEKR-----------LEKQRELERQREEERrkeierr 483
Cdd:pfam17380  286 ERQQQEKFEKMEQERLRQEKEEKAREVERRRKLEEAEKARQAEMDRQaaiyaeqermaMERERELERIRQEER------- 358

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1804876928  484 eaaKQELERQRR----LEWERIRRQELLNQRNREQEEIVR--LNSKKKSLHLELEALNGKHQQISGRLQDVRLRKQTQKT 557
Cdd:pfam17380  359 ---KRELERIRQeeiaMEISRMRELERLQMERQQKNERVRqeLEAARKVKILEEERQRKIQQQKVEMEQIRAEQEEARQR 435

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1804876928  558 EIEVLDKQCDLEIMEIKQLQQELQDYQNKLiylvpeKQLLNERIKNmqlgntpdlgidllhKKSLEKEELCQRLKEQLD- 636
Cdd:pfam17380  436 EVRRLEEERAREMERVRLEEQERQQQVERL------RQQEEERKRK---------------KLELEKEKRDRKRAEEQRr 494

                          250       260       270       280       290       300       310       320
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1804876928  637 -ALEKETASKLSEMDSFNNQLKcgnmddsvlqcllsllsclnnlfLLLKELRESYNTqqLALEQlhkiKRDKLKEIERKR 715
Cdd:pfam17380  495 kILEKELEERKQAMIEEERKRK-----------------------LLEKEMEERQKA--IYEEE----RRREAEEERRKQ 545

                          330       340       350       360       370       380       390
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 1804876928  716 SELIQKKKLEdEAIRKAKQGKENLwrESLRKEEEEKQKRLQEEKTQekvqeeerkveeKQCEPASALVNYKALYR 790
Cdd:pfam17380  546 QEMEERRRIQ-EQMRKATEERSRL--EAMEREREMMRQIVESEKAR------------AEYEATTPITTIKPIYR 605

Src Homology 3 domain of Myosin XV; This subfamily is composed of proteins with similarity to Myosin XVa. Myosin XVa is an unconventional myosin that is critical for the normal growth of mechanosensory stereocilia of inner ear hair cells. Mutations in the myosin XVa gene are associated with nonsyndromic hearing loss. Myosin XVa contains a unique N-terminal extension followed by a motor domain, light chain-binding IQ motifs, and a tail consisting of a pair of MyTH4-FERM tandems separated by a SH3 domain, and a PDZ domain. SH3 domains bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs; they play a role in the regulation of enzymes by intramolecular interactions, changing the subcellular localization of signal pathway components and mediate multiprotein complex assemblies.

Pssm-ID: 212817 [Multi-domain] Cd Length: 56 Bit Score: 53.87 E-value: 4.80e-09

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|...
gi 1804876928  786 KALYRFEARSHDEMSFNSGDIIQV-DEKTIGEPGWLYGSFQGNFGWFPCNYVE 837
Cdd:cd11884      3 VAVRAYITRDQTLLSFHKGDVIKLlPKEGPLDPGWLFGTLDGRSGAFPKEYVQ 55

Third N-terminal Src homology 3 domain of Dynamin Binding Protein, also called Tuba; DNMBP or Tuba is a cdc42-specific guanine nucleotide exchange factor (GEF) that contains four N-terminal SH3 domains, a central RhoGEF [or Dbl homology (DH)] domain followed by a Bin/Amphiphysin/Rvs (BAR) domain, and two C-terminal SH3 domains. It provides a functional link between dynamin and key regulatory proteins of the actin cytoskeleton. It plays an important role in regulating cell junction configuration. The four N-terminal SH3 domains of DNMBP binds the GTPase dynamin, which plays an important role in the fission of endocytic vesicles. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212730 Cd Length: 51 Bit Score: 53.51 E-value: 4.94e-09

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|.
gi 1804876928 1152 QVIAMYDYVANNEDELNFSKGQLINVLNKDDPDWWQGEINGVTGLFPSNYV 1202
Cdd:cd11796      1 QARVLQDLSAQLDEELDLREGDVVTITGILDKGWFRGELNGRRGIFPEGFV 51

Second C-terminal Src homology 3 domain of Fungal Actin-binding protein 1; Abp1 is an adaptor protein that functions in receptor-mediated endocytosis and vesicle trafficking. It contains an N-terminal actin-binding module, the actin-depolymerizing factor (ADF) homology domain, a central proline-rich region, and a C-terminal SH3 domain (many yeast Abp1 proteins contain two C-terminal SH3 domains). Yeast Abp1 also contains two acidic domains that bind directly to the Arp2/3 complex, which is required to initiate actin polymerization. The SH3 domain of yeast Abp1 binds and localizes the kinases, Ark1p and Prk1p, which facilitate actin patch disassembly following vesicle internalization. It also mediates the localization to the actin patch of the synaptojanin-like protein, Sjl2p, which plays a key role in endocytosis. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212894 [Multi-domain] Cd Length: 53 Bit Score: 53.68 E-value: 5.30e-09

                           10        20        30        40
                   ....*....|....*....|....*....|....*....|....*....
gi 1804876928 1009 ALYSYSSVEPGDLTFIEGEEIL-VTQKDGEWWTGSIGDRTGIFPSNYVK 1056
Cdd:cd11961      4 ALYDYDAAEDNELSFFENDKIInIEFVDDDWWLGECHGSRGLFPSNYVE 52

Src homology 3 domain of Protein kinase C and Casein kinase Substrate in Neurons (PACSIN) proteins; PACSINs, also called Synaptic dynamin-associated proteins (Syndapins), act as regulators of cytoskeletal and membrane dynamics. They bind both dynamin and Wiskott-Aldrich syndrome protein (WASP), and may provide direct links between the actin cytoskeletal machinery through WASP and dynamin-dependent endocytosis. Vetebrates harbor three isoforms with distinct expression patterns and specific functions. PACSINs contain an N-terminal F-BAR domain and a C-terminal SH3 domain. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212777 [Multi-domain] Cd Length: 53 Bit Score: 53.58 E-value: 5.70e-09

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....
gi 1804876928  786 KALYRFEARSHDEMSFNSGDIIQ--VDEKtigEPGWLYGSFQGNFGWFPCNYVE 837
Cdd:cd11843      3 RALYDYEGQESDELSFKAGDILTklEEED---EQGWCKGRLDGRVGLYPANYVE 53

First Src Homology 3 domain of SH3 domain containing ring finger protein 1, an E3 ubiquitin-protein ligase; SH3RF1 is also called POSH (Plenty of SH3s) or SH3MD2 (SH3 multiple domains protein 2). It is a scaffold protein that acts as an E3 ubiquitin-protein ligase. It plays a role in calcium homeostasis through the control of the ubiquitin domain protein Herp. It may also have a role in regulating death receptor mediated and JNK mediated apoptosis. SH3RF1 also enhances the ubiquitination of ROMK1 potassium channel resulting in its increased endocytosis. It contains an N-terminal RING finger domain and four SH3 domains. This model represents the first SH3 domain, located at the N-terminal half, of SH3RF1. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212860 Cd Length: 54 Bit Score: 53.42 E-value: 5.91e-09

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|
gi 1804876928 1155 AMYDYVANNEDELNFSKGQLINVLNKDDPDWWQGEINGVTGLFPSNYVKM 1204
Cdd:cd11927      5 ALYNYEGKEPGDLKFSKGDIIILRRQVDENWYHGEVNGIHGFFPTNFVQI 54

First Src Homology 3 domain of Sorbin and SH3 domain containing 2 (Sorbs2), also called Arg-binding protein 2 (ArgBP2); Sorbs2 or ArgBP2 is an adaptor protein containing one sorbin homology (SoHo) and three SH3 domains. It regulates actin-dependent processes including cell adhesion, morphology, and migration. It is expressed in many tissues and is abundant in the heart. Like vinexin, it is found in focal adhesion where it interacts with vinculin and afadin. It also localizes in epithelial cell stress fibers and in cardiac muscle cell Z-discs. Sorbs2 has been implicated to play roles in the signaling of c-Arg, Akt, and Pyk2. Other interaction partners of Sorbs2 include c-Abl, flotillin, spectrin, dynamin 1/2, synaptojanin, PTP-PEST, among others. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212853 [Multi-domain] Cd Length: 55 Bit Score: 53.48 E-value: 6.68e-09

                           10        20        30        40
                   ....*....|....*....|....*....|....*....|....*....
gi 1804876928 1155 AMYDYVANNEDELNFSKGQLINVLNKDDPDWWQGEINGVTGLFPSNYVK 1203
Cdd:cd11920      5 AVYDFKAQTSKELSFKKGDTVYILRKIDQNWYEGEHHGRVGIFPISYVE 53

Src homology 3 domain of Myosins Ie, If, and similar proteins; Myosins Ie (MyoIe) and If (MyoIf) are nonmuscle, unconventional, long tailed, class I myosins containing an N-terminal motor domain and a myosin tail with TH1, TH2, and SH3 domains. MyoIe interacts with the endocytic proteins, dynamin and synaptojanin-1, through its SH3 domain; it may play a role in clathrin-dependent endocytosis. In the kidney, MyoIe is critical for podocyte function and normal glomerular filtration. Mutations in MyoIe is associated with focal segmental glomerulosclerosis, a disease characterized by massive proteinuria and progression to end-stage kidney disease. MyoIf is predominantly expressed in the immune system; it plays a role in immune cell motility and innate immunity. Mutations in MyoIf may be associated with the loss of hearing. The MyoIf gene has also been found to be fused to the MLL (Mixed lineage leukemia) gene in infant acute myeloid leukemias (AML). SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212761 [Multi-domain] Cd Length: 53 Bit Score: 53.19 E-value: 6.68e-09

                           10        20        30        40
                   ....*....|....*....|....*....|....*....|....*...
gi 1804876928 1009 ALYSYSSVEPGDLTFIEGEEILVTQKDGE-WWTGSIGDRTGIFPSNYV 1055
Cdd:cd11827      4 ALYAYDAQDTDELSFNEGDIIEILKEDPSgWWTGRLRGKEGLFPGNYV 51

N-terminal Src homology 3 domain of GRB2-related adaptor protein 2; GRAP2 is also called GADS (GRB2-related adapter downstream of Shc), GrpL, GRB2L, Mona, or GRID (Grb2-related protein with insert domain). It is expressed specifically in the hematopoietic system. It plays an important role in T cell receptor (TCR) signaling by promoting the formation of the SLP-76:LAT complex, which couples the TCR to the Ras pathway. It also have roles in antigen-receptor and tyrosine kinase mediated signaling. GRAP2 is unique from other GRB2-like adaptor proteins in that it can be regulated by caspase cleavage. It contains an N-terminal SH3 domain, a central SH2 domain, and a C-terminal SH3 domain. The N-terminal SH3 domain of the related protein GRB2 binds to Sos and Sos-derived proline-rich peptides. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212880 [Multi-domain] Cd Length: 52 Bit Score: 53.26 E-value: 6.83e-09

                           10        20        30        40
                   ....*....|....*....|....*....|....*....|....*...
gi 1804876928 1155 AMYDYVANNEDELNFSKGQLINVLNKDDpDWWQGEINGVTGLFPSNYV 1202
Cdd:cd11947      4 GKFDFTASGEDELSFKKGDVLKILSSDD-IWFKAELNGEEGYVPKNFV 50

RecF/RecN/SMC N terminal domain; This domain is found at the N terminus of SMC proteins. The SMC (structural maintenance of chromosomes) superfamily proteins have ATP-binding domains at the N- and C-termini, and two extended coiled-coil domains separated by a hinge in the middle. The eukaryotic SMC proteins form two kind of heterodimers: the SMC1/SMC3 and the SMC2/SMC4 types. These heterodimers constitute an essential part of higher order complexes, which are involved in chromatin and DNA dynamics. This family also includes the RecF and RecN proteins that are involved in DNA metabolism and recombination.

Pssm-ID: 426784 [Multi-domain] Cd Length: 1161 Bit Score: 61.14 E-value: 6.96e-09

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1804876928  384 QKIQEEEPQKKLPVTFEDKRKANYERGNVELEKRRQALMEQQQREAERK---AQKEKEEWERKQRELQEQEWKKQLELEK 460
Cdd:pfam02463  324 KKAEKELKKEKEEIEELEKELKELEIKREAEEEEEEELEKLQEKLEQLEeelLAKKKLESERLSSAAKLKEEELELKSEE 403

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1804876928  461 RLEKQRELERQREEERRKEIERREAAKQELERQRRLE---------WERIRRQELLNQRNREQEEIVRLNSKKKSLHLEL 531
Cdd:pfam02463  404 EKEAQLLLELARQLEDLLKEEKKEELEILEEEEESIElkqgklteeKEELEKQELKLLKDELELKKSEDLLKETQLVKLQ 483

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1804876928  532 EAL---------------------------NGKHQQISGRLQDVRLRKQTQKTEIEVLD-KQCDLEIMEIKQLQQELQDY 583
Cdd:pfam02463  484 EQLelllsrqkleersqkeskarsglkvllALIKDGVGGRIISAHGRLGDLGVAVENYKvAISTAVIVEVSATADEVEER 563

                          250       260       270       280       290       300       310       320
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1804876928  584 QNKLIYLVPEKQLLNERIKNMQLGNTPDLGIDLL-----------HKKSLEKEE-------LCQRLKEQLDALEKETASK 645
Cdd:pfam02463  564 QKLVRALTELPLGARKLRLLIPKLKLPLKSIAVLeidpilnlaqlDKATLEADEddkrakvVEGILKDTELTKLKESAKA 643

                          330       340       350       360       370       380       390       400
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1804876928  646 LSEMDSFNNQLKCGNMDDSVLQCLLSLLSCLNNLFLLLKELRES--------YNTQQLALEQLHKIKRDK-----LKEIE 712
Cdd:pfam02463  644 KESGLRKGVSLEEGLAEKSEVKASLSELTKELLEIQELQEKAESelakeeilRRQLEIKKKEQREKEELKklkleAEELL 723

                          410       420       430       440       450       460
                   ....*....|....*....|....*....|....*....|....*....|....*....|...
gi 1804876928  713 RKRSELIQKKKLEDEAIRKAKQGKENLWRESLRKEEEEKQKRLQEEKTQEKVQEEERKVEEKQ 775
Cdd:pfam02463  724 ADRVQEAQDKINEELKLLKQKIDEEEEEEEKSRLKKEEKEEEKSELSLKEKELAEEREKTEKL 786

chromosome segregation protein SMC, common bacterial type; SMC (structural maintenance of chromosomes) proteins bind DNA and act in organizing and segregating chromosomes for partition. SMC proteins are found in bacteria, archaea, and eukaryotes. This family represents the SMC protein of most bacteria. The smc gene is often associated with scpB (TIGR00281) and scpA genes, where scp stands for segregation and condensation protein. SMC was shown (in Caulobacter crescentus) to be induced early in S phase but present and bound to DNA throughout the cell cycle. [Cellular processes, Cell division, DNA metabolism, Chromosome-associated proteins]

Pssm-ID: 274008 [Multi-domain] Cd Length: 1179 Bit Score: 61.23 E-value: 7.08e-09

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1804876928  413 ELEKRRQALMEQQQ--REAERKAQKEKEEWERKQRELQEQewkkQLELEKRLEKqrelerqrEEERRKEIER--REAAKQ 488
Cdd:TIGR02168  695 ELEKALAELRKELEelEEELEQLRKELEELSRQISALRKD----LARLEAEVEQ--------LEERIAQLSKelTELEAE 762

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1804876928  489 ELERQRRLEWERIRRQELLNQRNREQEEIVRLNSKKKSLHLELEALNGKHQQISGRLQDVRLRKQTQKTEIEVLDKqcdl 568
Cdd:TIGR02168  763 IEELEERLEEAEEELAEAEAEIEELEAQIEQLKEELKALREALDELRAELTLLNEEAANLRERLESLERRIAATER---- 838

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1804876928  569 eimEIKQLQQELQDYQNKLIYLVPEKQLLNERIKNMQlgntpdLGIDLLHKKSLEKEELCQRLKEQLDALEKETASKLSE 648
Cdd:TIGR02168  839 ---RLEDLEEQIEELSEDIESLAAEIEELEELIEELE------SELEALLNERASLEEALALLRSELEELSEELRELESK 909

                          250       260       270       280       290       300       310       320
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1804876928  649 MDSFNNQLKcgNMDDSVLQCLLSLLSCLNNLFLLLKELRESYNTQQLALEQLHKIKRDKLKEIERKRSELiqKKKLED-- 726
Cdd:TIGR02168  910 RSELRRELE--ELREKLAQLELRLEGLEVRIDNLQERLSEEYSLTLEEAEALENKIEDDEEEARRRLKRL--ENKIKElg 985

                          330       340       350       360
                   ....*....|....*....|....*....|....*....|....*..
gi 1804876928  727 ----EAIRKAKQGKEnlwreslRKEEEEKQKR-LQEEKTQ-EKVQEE 767
Cdd:TIGR02168  986 pvnlAAIEEYEELKE-------RYDFLTAQKEdLTEAKETlEEAIEE 1025

chromosome segregation protein SMC, common bacterial type; SMC (structural maintenance of chromosomes) proteins bind DNA and act in organizing and segregating chromosomes for partition. SMC proteins are found in bacteria, archaea, and eukaryotes. This family represents the SMC protein of most bacteria. The smc gene is often associated with scpB (TIGR00281) and scpA genes, where scp stands for segregation and condensation protein. SMC was shown (in Caulobacter crescentus) to be induced early in S phase but present and bound to DNA throughout the cell cycle. [Cellular processes, Cell division, DNA metabolism, Chromosome-associated proteins]

Pssm-ID: 274008 [Multi-domain] Cd Length: 1179 Bit Score: 60.84 E-value: 7.27e-09

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1804876928  434 QKEKEEWERKQRELQEQEWKKQLELeKRLEKQrelerqreeerrkeIErreaAKQELERQRRLEWERIRRQ--ELLNQRN 511
Cdd:TIGR02168  676 RREIEELEEKIEELEEKIAELEKAL-AELRKE--------------LE----ELEEELEQLRKELEELSRQisALRKDLA 736

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1804876928  512 REQEEIVRLNSKKKSLHLELEALNGKHQQISGRLQDVRLRKQTQKTEIEVLDKQcdleimeIKQLQQELQDYQNKLIYLV 591
Cdd:TIGR02168  737 RLEAEVEQLEERIAQLSKELTELEAEIEELEERLEEAEEELAEAEAEIEELEAQ-------IEQLKEELKALREALDELR 809

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1804876928  592 PEKQLLNERIKNMQlgntpdLGIDLLHKKSLEKEELCQRLKEQLDALEKETASKLSEMDSFNNQLkcgnmddSVLQCLls 671
Cdd:TIGR02168  810 AELTLLNEEAANLR------ERLESLERRIAATERRLEDLEEQIEELSEDIESLAAEIEELEELI-------EELESE-- 874

                          250       260       270       280       290       300       310       320
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1804876928  672 llsclnnlfllLKELRESYNTQQLALEQLHK---IKRDKLKEIERKRSELIQKKKLedeaiRKAKQGKENLWRESLRKEE 748
Cdd:TIGR02168  875 -----------LEALLNERASLEEALALLRSeleELSEELRELESKRSELRRELEE-----LREKLAQLELRLEGLEVRI 938

                          330       340
                   ....*....|....*....|....*....
gi 1804876928  749 EEKQKRLQEE--KTQEKVQEEERKVEEKQ 775
Cdd:TIGR02168  939 DNLQERLSEEysLTLEEAEALENKIEDDE 967

C-terminal Src homology 3 domain of GRB2-related adaptor protein 2; GRAP2 is also called GADS (GRB2-related adapter downstream of Shc), GrpL, GRB2L, Mona, or GRID (Grb2-related protein with insert domain). It is expressed specifically in the hematopoietic system. It plays an important role in T cell receptor (TCR) signaling by promoting the formation of the SLP-76:LAT complex, which couples the TCR to the Ras pathway. It also has roles in antigen-receptor and tyrosine kinase mediated signaling. GRAP2 is unique from other GRB2-like adaptor proteins in that it can be regulated by caspase cleavage. It contains an N-terminal SH3 domain, a central SH2 domain, and a C-terminal SH3 domain. The C-terminal SH3 domain of GRAP2 binds to different motifs found in substrate peptides including the typical PxxP motif in hematopoietic progenitor kinase 1 (HPK1), the RxxK motif in SLP-76 and HPK1, and the RxxxxK motif in phosphatase-like protein HD-PTP. SH3 domains are protein interaction domains that typically bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212883 [Multi-domain] Cd Length: 53 Bit Score: 53.29 E-value: 7.35e-09

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|..
gi 1804876928  786 KALYRFEARSHDEMSFNSGDIIQVDEKTigEPGWLYGSFQGNFGWFPCNYVE 837
Cdd:cd11950      3 RALYDFEALEDDELGFNSGDVIEVLDSS--NPSWWKGRLHGKLGLFPANYVA 52

Fifth Src homology 3 domain (or SH3E) of Intersectin; Intersectins (ITSNs) are adaptor proteins that function in exo- and endocytosis, actin cytoskeletal reorganization, and signal transduction. They are essential for initiating clathrin-coated pit formation. They bind to many proteins through their multidomain structure and facilitate the assembly of multimeric complexes. Vertebrates contain two ITSN proteins, ITSN1 and ITSN2, which exist in alternatively spliced short and long isoforms. The short isoforms contain two Eps15 homology domains (EH1 and EH2), a coiled-coil region and five SH3 domains (SH3A-E), while the long isoforms, in addition, contain RhoGEF (also called Dbl-homologous or DH), Pleckstrin homology (PH) and C2 domains. ITSN1 and ITSN2 are both widely expressed, with variations depending on tissue type and stage of development. The fifth SH3 domain (or SH3E) of ITSN1 has been shown to bind many protein partners including SGIP1, Sos1, dynamin1/2, CIN85, c-Cbl, SHIP2, N-WASP, and synaptojanin-1, among others. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212774 [Multi-domain] Cd Length: 53 Bit Score: 53.19 E-value: 7.44e-09

                           10        20        30        40
                   ....*....|....*....|....*....|....*....|....*....
gi 1804876928  926 ALCSWTAKKDNHLNFSKHDIITVLEQQE-NWWFGEVHGGRGWFPKSYVK 973
Cdd:cd11840      4 ALFPYTAQNEDELSFQKGDIINVLSKDDpDWWRGELNGQTGLFPSNYVE 52

Second Src Homology 3 domain of Sorbin and SH3 domain containing (Sorbs) proteins and similar domains; This family, also called the vinexin family, is composed predominantly of adaptor proteins containing one sorbin homology (SoHo) and three SH3 domains. Members include the second SH3 domains of Sorbs1 (or ponsin), Sorbs2 (or ArgBP2), Vinexin (or Sorbs3), and similar domains. They are involved in the regulation of cytoskeletal organization, cell adhesion, and growth factor signaling. Members of this family bind multiple partners including signaling molecules like c-Abl, c-Arg, Sos, and c-Cbl, as well as cytoskeletal molecules such as vinculin and afadin. They may have overlapping functions. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212716 [Multi-domain] Cd Length: 53 Bit Score: 53.12 E-value: 7.71e-09

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|..
gi 1804876928 1152 QVIAMYDYVANNEDELNFSKGQLINVLNKDDPDWWQGEINGVTGLFPSNYVK 1203
Cdd:cd11782      1 EARAKYNFNADTGVELSFRKGDVITLTRRVDENWYEGRIGGRQGIFPVSYVQ 52

DNA double-strand break repair ATPase Rad50;

Pssm-ID: 235175 [Multi-domain] Cd Length: 880 Bit Score: 60.85 E-value: 7.98e-09

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1804876928  429 AERKAQKEKEEWERKQRELqEQEWKKQLELEKRLEKQrelerqreeerrkeierreaaKQELERQRR----LEWERIRRQ 504
Cdd:PRK03918   163 AYKNLGEVIKEIKRRIERL-EKFIKRTENIEELIKEK---------------------EKELEEVLReineISSELPELR 220

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1804876928  505 ELLNQRNREQEEIVRLNSKKKSLHLELEALNGKHQQISGRLQDVRLRKQTQKTEIEVLDKQCDlEIMEIK-------QLQ 577
Cdd:PRK03918   221 EELEKLEKEVKELEELKEEIEELEKELESLEGSKRKLEEKIRELEERIEELKKEIEELEEKVK-ELKELKekaeeyiKLS 299

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1804876928  578 QELQDYQNKLIYLVPEKQLLNERIKNMQlgntpdLGIDLLHKKSLEKEELCQRLKEQLDALEK---------ETASKLSE 648
Cdd:PRK03918   300 EFYEEYLDELREIEKRLSRLEEEINGIE------ERIKELEEKEERLEELKKKLKELEKRLEEleerhelyeEAKAKKEE 373

                          250       260       270       280       290       300       310       320
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1804876928  649 MDSFNNQLKCGNMDDSV--LQCLLSLLSCLNNLFLLLK----ELRESYNTQQLALEQLHKIKRD------KLKEIERKrs 716
Cdd:PRK03918   374 LERLKKRLTGLTPEKLEkeLEELEKAKEEIEEEISKITarigELKKEIKELKKAIEELKKAKGKcpvcgrELTEEHRK-- 451

                          330       340       350       360       370       380
                   ....*....|....*....|....*....|....*....|....*....|....*....|.
gi 1804876928  717 ELIQKKKLEDEAIRKAKQGKENLWREsLRKEEEEKQKRLQEEKT---QEKVQEEERKVEEK 774
Cdd:PRK03918   452 ELLEEYTAELKRIEKELKEIEEKERK-LRKELRELEKVLKKESElikLKELAEQLKELEEK 511

C-terminal Src Homology 3 domain of Nebulin; Nebulin is a giant filamentous protein (600-900 kD) that is expressed abundantly in skeletal muscle. It binds to actin thin filaments and regulates its assembly and function. Nebulin was thought to be part of a molecular ruler complex that is critical in determining the lengths of actin thin filaments in skeletal muscle since its length, which varies due to alternative splicing, correlates with the length of thin filaments in various muscle types. Recent studies indicate that nebulin regulates thin filament length by stabilizing the filaments and preventing depolymerization. Mutations in nebulin can cause nemaline myopathy, characterized by muscle weakness which can be severe and can lead to neonatal lethality. Nebulin contains an N-terminal LIM domain, many nebulin repeats/super repeats, and a C-terminal SH3 domain. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212866 [Multi-domain] Cd Length: 58 Bit Score: 53.47 E-value: 8.38e-09

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....*..
gi 1804876928  785 YKALYRFEARSHDEMSFNSGDIIqVDEKTIGEpGWLYGSFQ--GNFGWFPCNYVEKM 839
Cdd:cd11933      4 FRAMYDYRAADDDEVSFKDGDTI-VNVQTIDE-GWMYGTVQrtGKTGMLPANYVEAI 58

Src homology 3 domain of Cortactin and related proteins; This subfamily includes cortactin, Abp1 (actin-binding protein 1), hematopoietic lineage cell-specific protein 1 (HS1), and similar proteins. These proteins are involved in regulating actin dynamics through direct or indirect interaction with the Arp2/3 complex, which is required to initiate actin polymerization. They all contain at least one C-terminal SH3 domain. Cortactin and HS1 bind Arp2/3 and actin through an N-terminal region that contains an acidic domain and several copies of a repeat domain found in cortactin and HS1. Abp1 binds actin via an N-terminal actin-depolymerizing factor (ADF) homology domain. Yeast Abp1 binds Arp2/3 directly through two acidic domains. Mammalian Abp1 does not directly interact with Arp2/3; instead, it regulates actin dynamics indirectly by interacting with dynamin and WASP family proteins. The C-terminal region of these proteins acts as an adaptor or scaffold that can connect membrane trafficking and signaling proteins that bind the SH3 domain within the actin network. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212753 [Multi-domain] Cd Length: 54 Bit Score: 53.09 E-value: 8.61e-09

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....*..
gi 1804876928  786 KALYRFEARSHDEMSFNSGDII----QVDEktigepGWLYGSF-QGNFGWFPCNYVE 837
Cdd:cd11819      3 KALYDYQAAEDNEISFVEGDIItqieQIDE------GWWLGVNaKGQKGLFPANYVE 53

Src homology 3 domain of Slit-Robo GTPase Activating Proteins 1, 2, and 3; srGAP1, also called Rho GTPase-Activating Protein 13 (ARHGAP13), is a Cdc42- and RhoA-specific GAP and is expressed later in the development of central nervous system tissues. srGAP2 is expressed in zones of neuronal differentiation. It plays a role in the regeneration of neurons and axons. srGAP3, also called MEGAP (MEntal disorder associated GTPase-Activating Protein), is a Rho GAP with activity towards Rac1 and Cdc42. It impacts cell migration by regulating actin and microtubule cytoskeletal dynamics. The association between srGAP3 haploinsufficiency and mental retardation is under debate. srGAPs are Rho GAPs that interact with Robo1, the transmembrane receptor of Slit proteins. Slit proteins are secreted proteins that control axon guidance and the migration of neurons and leukocytes. srGAPs contain an N-terminal F-BAR domain, a Rho GAP domain, and a C-terminal SH3 domain. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212888 [Multi-domain] Cd Length: 53 Bit Score: 53.02 E-value: 8.65e-09

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|.
gi 1804876928 1152 QVIAMYDYVANNEDELNFSKGQLINVLNKDDPDWWQGEINGVTGLFPSNYV 1202
Cdd:cd11955      1 EAIAKFDYVGRSARELSFKKGASLLLYHRASDDWWEGRHNGIDGLVPHQYI 51

Chromosome segregation ATPase Smc [Cell cycle control, cell division, chromosome partitioning];

Pssm-ID: 440809 [Multi-domain] Cd Length: 983 Bit Score: 60.72 E-value: 8.85e-09

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1804876928  401 DKRKANYERGNVELEKRRQALMEQQQR--EAERKAQKEKEEWERKQRELQEQEWKKQLELEKRLEKQRELERQREEERRK 478
Cdd:COG1196    270 EELRLELEELELELEEAQAEEYELLAElaRLEQDIARLEERRRELEERLEELEEELAELEEELEELEEELEELEEELEEA 349

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1804876928  479 EIERREAAKQELERQRRLEWERIRRQELLNQRNREQEEIVRLNSKKKSLHLELEALNGKHQQISGRLQDVRLRKQTQKTE 558
Cdd:COG1196    350 EEELEEAEAELAEAEEALLEAEAELAEAEEELEELAEELLEALRAAAELAAQLEELEEAEEALLERLERLEEELEELEEA 429

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1804876928  559 IEVLDKQCDLEIMEIKQLQQELQDYQNKLIYLVPEKQLLNERIKNMQlgntpDLGIDLLHKKSLEKEELcQRLKEQLDAL 638
Cdd:COG1196    430 LAELEEEEEEEEEALEEAAEEEAELEEEEEALLELLAELLEEAALLE-----AALAELLEELAEAAARL-LLLLEAEADY 503

                          250       260       270       280       290       300       310       320
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1804876928  639 EKETASKLSEMDSFNNQLKCGnmDDSVLQCLLSLLSCLNNLFLLLKELRESYNTQQLALEQLHKIKRDKLKEIERKRSEL 718
Cdd:COG1196    504 EGFLEGVKAALLLAGLRGLAG--AVAVLIGVEAAYEAALEAALAAALQNIVVEDDEVAAAAIEYLKAAKAGRATFLPLDK 581

                          330       340       350       360
                   ....*....|....*....|....*....|....*....|
gi 1804876928  719 IQKKKLEDEAIRKAKQGKENLWRESLRKEEEEKQKRLQEE 758
Cdd:COG1196    582 IRARAALAAALARGAIGAAVDLVASDLREADARYYVLGDT 621

Src Homology 3 domain of Mixed Lineage Kinase 4; MLK4 is a Serine/Threonine Kinase (STK), catalyzing the transfer of the gamma-phosphoryl group from ATP to S/T residues on protein substrates. MLKs act as mitogen-activated protein kinase kinase kinases (MAP3Ks, MKKKs, MAPKKKs), which phosphorylate and activate MAPK kinases (MAPKKs or MKKs or MAP2Ks), which in turn phosphorylate and activate MAPKs during signaling cascades that are important in mediating cellular responses to extracellular signals. MLKs play roles in immunity and inflammation, as well as in cell death, proliferation, and cell cycle regulation. The specific function of MLK4 is yet to be determined. Mutations in the kinase domain of MLK4 have been detected in colorectal cancers. MLK4 contains an SH3 domain, a catalytic kinase domain, a leucine zipper, a proline-rich region, and a CRIB domain that mediates binding to GTP-bound Cdc42 and Rac. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212991 [Multi-domain] Cd Length: 58 Bit Score: 53.02 E-value: 9.12e-09

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....*
gi 1804876928  785 YKALYRFEARSHDEMSFNSGDIIQV---DEKTIGEPGWLYGSFQGNFGWFPCNYV 836
Cdd:cd12058      2 WTALYDYEASGEDELSLRRGDVVEVlsqDAAVSGDDGWWAGKIRHRLGIFPANYV 56

C-terminal Src homology 3 domain of GRB2-related adaptor protein 2; GRAP2 is also called GADS (GRB2-related adapter downstream of Shc), GrpL, GRB2L, Mona, or GRID (Grb2-related protein with insert domain). It is expressed specifically in the hematopoietic system. It plays an important role in T cell receptor (TCR) signaling by promoting the formation of the SLP-76:LAT complex, which couples the TCR to the Ras pathway. It also has roles in antigen-receptor and tyrosine kinase mediated signaling. GRAP2 is unique from other GRB2-like adaptor proteins in that it can be regulated by caspase cleavage. It contains an N-terminal SH3 domain, a central SH2 domain, and a C-terminal SH3 domain. The C-terminal SH3 domain of GRAP2 binds to different motifs found in substrate peptides including the typical PxxP motif in hematopoietic progenitor kinase 1 (HPK1), the RxxK motif in SLP-76 and HPK1, and the RxxxxK motif in phosphatase-like protein HD-PTP. SH3 domains are protein interaction domains that typically bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212883 [Multi-domain] Cd Length: 53 Bit Score: 52.91 E-value: 9.48e-09

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|
gi 1804876928 1009 ALYSYSSVEPGDLTFIEGEEILVTQK-DGEWWTGSIGDRTGIFPSNYVKP 1057
Cdd:cd11950      4 ALYDFEALEDDELGFNSGDVIEVLDSsNPSWWKGRLHGKLGLFPANYVAP 53

C-terminal Src Homology 3 domain of NADPH oxidase activator 1; Noxa1 is a homolog of p67phox and is a cytosolic subunit of the nonphagocytic NADPH oxidase complex Nox1, which catalyzes the transfer of electrons from NADPH to molecular oxygen to form superoxide. Noxa1 is co-expressed with Nox1 in colon, stomach, uterus, prostate, and vascular smooth muscle cells, consistent with its regulatory role. It does not interact with p40phox, unlike p67phox, making Nox1 activity independent of p40phox, unlike Nox2. Noxa1 contains TPR, PB1, and C-terminal SH3 domains, but lacks the central SH3 domain that is present in p67phox. The TPR domain binds activated GTP-bound Rac. The C-terminal SH3 domain binds the polyproline motif found at the C-terminus of Noxo1, a homolog of p47phox. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212980 Cd Length: 53 Bit Score: 52.90 E-value: 9.91e-09

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|.
gi 1804876928 1152 QVIAMYDYVANNEDELNFSKGQLINVLNKDDPDWWQGEINGVTGLFPSNYV 1202
Cdd:cd12047      1 RMVAQHDYSAQGPEDLEFSQGDTIDILSEVNQEWLEGHCDGRIGIFPKCFA 51

Src homology 3 domain of Nitric Oxide Synthase TRaffic INducer; Nostrin is expressed in endothelial and epithelial cells and is involved in the regulation, trafficking and targeting of endothelial NOS (eNOS). It facilitates the endocytosis of eNOS by coordinating the functions of dynamin and the Wiskott-Aldrich syndrome protein (WASP). Increased expression of Nostrin may be correlated to preeclampsia. Nostrin contains an N-terminal F-BAR domain and a C-terminal SH3 domain. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212757 [Multi-domain] Cd Length: 53 Bit Score: 52.73 E-value: 1.04e-08

                           10        20        30        40
                   ....*....|....*....|....*....|....*....|....*...
gi 1804876928 1009 ALYSYSSVEPGDLTFIEGEEILVTQKDGE-WWTGSIGDRTGIFPSNYV 1055
Cdd:cd11823      4 ALYSYTANREDELSLQPGDIIEVHEKQDDgWWLGELNGKKGIFPATYV 51

Src Homology 3 domain of eumetazoan Peroxisomal biogenesis factor 13; PEX13 is a peroxin and is required for protein import into the peroxisomal matrix and membrane. It is an integral membrane protein that is essential for the localization of PEX14 and the import of proteins containing the peroxisome matrix targeting signals, PTS1 and PTS2. Mutations of the PEX13 gene in humans lead to a wide range of peroxisome biogenesis disorders (PBDs), the most severe of which is known as Zellweger syndrome (ZS), a severe multisystem disorder characterized by hypotonia, psychomotor retardation, and neuronal migration defects. PEX13 contains two transmembrane regions and a C-terminal SH3 domain. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212798 Cd Length: 58 Bit Score: 53.02 E-value: 1.10e-08

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....*
gi 1804876928 1154 IAMYDYVANNEDELNFSKGQLINVLNKD----DPDWWQGEINGVT-GLFPSNYVK 1203
Cdd:cd11864      3 RAEYDFVAESEDELSFRAGDKLRLAPKElqprVRGWLLATVDGQKiGLVPANYVK 57

Src homology 3 domain of ArfGAP with SH3 domain, ankyrin repeat and PH domain containing proteins; ASAPs are Arf GTPase activating proteins (GAPs) and they function in regulating cell growth, migration, and invasion. They contain an N-terminal BAR domain, followed by a Pleckstrin homology (PH) domain, an Arf GAP domain, ankyrin (ANK) repeats, and a C-terminal SH3 domain. Vertebrates contain at least three members, ASAP1, ASAP2, and ASAP3, but some ASAP3 proteins do not seem to harbor a C-terminal SH3 domain. ASAP1 and ASAP2 show GTPase activating protein (GAP) activity towards Arf1 and Arf5. They do not show GAP activity towards Arf6, but are able to mediate Arf6 signaling by binding stably to GTP-Arf6. ASAP3 is an Arf6-specific GAP. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212755 [Multi-domain] Cd Length: 53 Bit Score: 52.70 E-value: 1.11e-08

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|
gi 1804876928 1009 ALYSYSSVEPGDLTFIEGEEILVT-QKDGEWWTGSI---GDRTGIFPSNY 1054
Cdd:cd11821      4 ALYDCQADNDDELTFSEGEIIVVTgEEDDEWWEGHIegdPSRRGVFPVSF 53

Second Src homology 3 domain of ADAM-binding protein Eve-1; Eve-1, also called SH3 domain-containing protein 19 (SH3D19) or EEN-binding protein (EBP), exists in multiple alternatively spliced isoforms. The longest isoform contains five SH3 domain in the C-terminal region and seven proline-rich motifs in the N-terminal region. It is abundantly expressed in skeletal muscle and heart, and may be involved in regulating the activity of ADAMs (A disintegrin and metalloproteases). Eve-1 interacts with EEN, an endophilin involved in endocytosis and may be the target of the MLL-EEN fusion protein that is implicated in leukemogenesis. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212749 [Multi-domain] Cd Length: 52 Bit Score: 52.57 E-value: 1.16e-08

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|
gi 1804876928 1154 IAMYDYVANNEDELNFSKGQLINVLNKDDPDWWQGEINGVTGLFPSNYVK 1203
Cdd:cd11815      3 VVLHDFPAEHSDDLSLNSGEIVYLLEKIDTEWYRGKCKNTTGIFPANHVK 52

Src homology 3 domain of ephexin-1-like SH3 domain containing Rho guanine nucleotide exchange factors; Members of this family contain RhoGEF (also called Dbl-homologous or DH), Pleckstrin Homology (PH), and C-terminal SH3 domains. They include the Rho guanine nucleotide exchange factors ARHGEF5, ARHGEF16, ARHGEF19, ARHGEF26, ARHGEF27 (also called ephexin-1), and similar proteins, and are also called ephexins because they interact directly with ephrin A receptors. GEFs interact with Rho GTPases via their DH domains to catalyze nucleotide exchange by stabilizing the nucleotide-free GTPase intermediate. They play important roles in neuronal development. The SH3 domains of ARHGEFs play an autoinhibitory role through intramolecular interactions with a proline-rich region N-terminal to the DH domain. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212727 [Multi-domain] Cd Length: 55 Bit Score: 52.72 E-value: 1.18e-08

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|...
gi 1804876928 1152 QVIAMYDYVANNEDELNFSKGQLINVLNKDDPDWWQGE--INGVTGLFPSNYV 1202
Cdd:cd11793      1 QVQCVHAYTAQQPDELTLEEGDVVNVLRKMPDGWYEGErlRDGERGWFPSSYT 53

Src homology 3 domain of ArfGAP with SH3 domain, ankyrin repeat and PH domain containing protein 2; ASAP2 is also called DDEF2 (Development and Differentiation Enhancing Factor 2), AMAP2, centaurin beta-3, or PAG3. It mediates the functions of Arf GTPases vial dual mechanisms: it exhibits GTPase activating protein (GAP) activity towards class I (Arf1) and II (Arf5) Arfs; and it binds class III Arfs (GTP-Arf6) stably without GAP activity. It binds paxillin and is implicated in Fcgamma receptor-mediated phagocytosis in macrophages and in cell migration. ASAP2 contains an N-terminal BAR domain, followed by a Pleckstrin homology (PH) domain, an Arf GAP domain, ankyrin (ANK) repeats, and a C-terminal SH3 domain. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212899 Cd Length: 56 Bit Score: 52.65 E-value: 1.23e-08

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....
gi 1804876928 1152 QVIAMYDYVANNEDELNFSKGQLINVLNKDDPDWWQGEING---VTGLFPSNYV 1202
Cdd:cd11966      1 RVKALYNCVADNPDELTFSEGEIIIVDGEEDKEWWIGHIDGeptRRGAFPVSFV 54

Src homology 3 domain of Endophilin-A; Endophilins play roles in synaptic vesicle formation, virus budding, mitochondrial morphology maintenance, receptor-mediated endocytosis inhibition, and endosomal sorting. They are classified into two types, A and B. Vertebrates contain three endophilin-A isoforms (A1, A2, and A3). Endophilin-A proteins are enriched in the brain and play multiple roles in receptor-mediated endocytosis. They tubulate membranes and regulate calcium influx into neurons to trigger the activation of the endocytic machinery. They are also involved in the sorting of plasma membrane proteins, actin filament assembly, and the uncoating of clathrin-coated vesicles for fusion with endosomes. Endophilins contain an N-terminal N-BAR domain (BAR domain with an additional N-terminal amphipathic helix), followed by a variable region containing proline clusters, and a C-terminal SH3 domain. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212737 [Multi-domain] Cd Length: 55 Bit Score: 52.65 E-value: 1.25e-08

                           10        20        30        40
                   ....*....|....*....|....*....|....*....|....*...
gi 1804876928 1009 ALYSYSSVEPGDLTFIEGEEI-LVTQKDGEWWTGSIGDRTGIFPSNYV 1055
Cdd:cd11803      5 ALYDFEPENEGELGFKEGDIItLTNQIDENWYEGMVNGQSGFFPVNYV 52

C-terminal (or second) Src Homology 3 domain of the p67phox subunit of NADPH oxidase; p67phox, also called Neutrophil cytosol factor 2 (NCF-2), is a cytosolic subunit of the phagocytic NADPH oxidase complex (also called Nox2 or gp91phox) which plays a crucial role in the cellular response to bacterial infection. NADPH oxidase catalyzes the transfer of electrons from NADPH to oxygen during phagocytosis forming superoxide and reactive oxygen species. p67phox plays a regulatory role and contains N-terminal TPR, first SH3 (or N-terminal or central SH3), PB1, and C-terminal SH3 domains. It binds, via its C-terminal SH3 domain, to a proline-rich region of p47phox and upon activation, this complex assembles with flavocytochrome b558, the Nox2-p22phox heterodimer. Concurrently, RacGTP translocates to the membrane and interacts with the TPR domain of p67phox, which leads to the activation of NADPH oxidase. The PB1 domain of p67phox binds to its partner PB1 domain in p40phox, and this facilitates the assembly of p47phox-p67phox at the membrane. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212979 [Multi-domain] Cd Length: 53 Bit Score: 52.50 E-value: 1.27e-08

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|.
gi 1804876928 1008 IALYSYSSVEPGDLTFIEGEEILVTQK-DGEWWTGSIGDRTGIFPSNYVKP 1057
Cdd:cd12046      3 VALFSYEASQPEDLEFQKGDVILVLSKvNEDWLEGQCKGKIGIFPSAFVED 53

Fifth Src homology 3 domain (or SH3E) of Intersectin-2; Intersectin-2 (ITSN2) is an adaptor protein that functions in exo- and endocytosis, actin cytoskeletal reorganization, and signal transduction. It plays a role in clathrin-coated pit (CCP) formation. It binds to many proteins through its multidomain structure and facilitate the assembly of multimeric complexes. ITSN2 also functions as a specific GEF for Cdc42 activation in epithelial morphogenesis, and is required in mitotic spindle orientation. It exists in alternatively spliced short and long isoforms. The short isoform contains two Eps15 homology domains (EH1 and EH2), a coiled-coil region and five SH3 domains (SH3A-E), while the long isoform, in addition, contains RhoGEF (also called Dbl-homologous or DH), Pleckstrin homology (PH) and C2 domains. The fifth SH3 domain (or SH3E) of ITSN2 is expected to bind protein partners, similar to ITSN1 which has been shown to bind many protein partners including SGIP1, Sos1, dynamin1/2, CIN85, c-Cbl, SHIP2, N-WASP, and synaptojanin-1, among others. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212929 [Multi-domain] Cd Length: 54 Bit Score: 52.68 E-value: 1.29e-08

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|..
gi 1804876928 1006 EYIALYSYSSVEPGDLTFIEGEEILVTQKDG-EWWTGSIGDRTGIFPSNYVK 1056
Cdd:cd11996      2 QVIAMYDYTANNEDELSFSKGQLINVLNKDDpDWWQGEINGVTGLFPSNYVK 53

C-terminal Src Homology 3 domain of the Nebulin family of proteins; Nebulin family proteins contain multiple nebulin repeats, and may contain an N-terminal LIM domain and/or a C-terminal SH3 domain. They have molecular weights ranging from 34 to 900 kD, depending on the number of nebulin repeats, and they all bind actin. They are involved in the regulation of actin filament architecture and function as stabilizers and scaffolds for cytoskeletal structures with which they associate, such as long actin filaments or focal adhesions. Nebulin family proteins that contain a C-terminal SH3 domain include the giant filamentous protein nebulin, nebulette, Lasp1, and Lasp2. Lasp2, also called LIM-nebulette, is an alternatively spliced variant of nebulette. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212723 [Multi-domain] Cd Length: 55 Bit Score: 52.32 E-value: 1.51e-08

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....*
gi 1804876928 1152 QVIAMYDYVANNEDELNFSKGQLINVLNKDDPDWWQG--EINGVTGLFPSNYVKM 1204
Cdd:cd11789      1 RYRAMYDYAAADDDEVSFQEGDVIINVEIIDDGWMEGtvQRTGQSGMLPANYVEL 55

First Src Homology 3 domain (SH3A) of CD2-associated protein; CD2AP, also called CMS (Cas ligand with Multiple SH3 domains) or METS1 (Mesenchyme-to-Epithelium Transition protein with SH3 domains), is a cytosolic adaptor protein that plays a role in regulating the cytoskeleton. It is critical in cell-to-cell union necessary for kidney function. It also stabilizes the contact between a T cell and antigen-presenting cells. It is primarily expressed in podocytes at the cytoplasmic face of the slit diaphragm and serves as a linker anchoring podocin and nephrin to the actin cytoskeleton. CD2AP contains three SH3 domains, a proline-rich region, and a C-terminal coiled-coil domain. All of these domains enable CD2AP to bind various protein partners and assemble complexes that have been implicated in many different functions. This alignment model represents the first SH3 domain (SH3A) of CD2AP. SH3A binds to the PXXXPR motif present in c-Cbl and the cytoplasmic domain of cell adhesion protein CD2. Its interaction with CD2 anchors CD2 at sites of cell contact. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212986 Cd Length: 56 Bit Score: 52.54 E-value: 1.62e-08

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|...
gi 1804876928 1152 QVIAMYDYVANNEDELNFSKGQLI-NVLNKDDPDWWQGEINGVTGLFPSNYVK 1203
Cdd:cd12053      1 EYIVEYDYDAVHEDELTIRVGEIIrNVKKLEEEGWLEGELNGRRGMFPDNFVK 53

First Src Homology 3 domain (SH3A) of CD2-associated protein and similar proteins; This subfamily is composed of the first SH3 domain (SH3A) of CD2AP, CIN85 (Cbl-interacting protein of 85 kDa), and similar domains. CD2AP and CIN85 are adaptor proteins that bind to protein partners and assemble complexes that have been implicated in T cell activation, kidney function, and apoptosis of neuronal cells. They also associate with endocytic proteins, actin cytoskeleton components, and other adaptor proteins involved in receptor tyrosine kinase (RTK) signaling. CD2AP and the main isoform of CIN85 contain three SH3 domains, a proline-rich region, and a C-terminal coiled-coil domain. All of these domains enable CD2AP and CIN85 to bind various protein partners and assemble complexes that have been implicated in many different functions. SH3A of both proteins bind to an atypical PXXXPR motif at the C-terminus of Cbl and the cytoplasmic domain of the cell adhesion protein CD2. CIN85 SH3A binds to internal proline-rich motifs within the proline-rich region; this intramolecular interaction serves as a regulatory mechanism to keep CIN85 in a closed conformation, preventing the recruitment of other proteins. CIN85 SH3A has also been shown to bind ubiquitin. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212806 [Multi-domain] Cd Length: 53 Bit Score: 52.27 E-value: 1.69e-08

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|..
gi 1804876928 1006 EYIALYSYSSVEPGDLTFIEGEEIL-VTQKDGEWWTGSIGDRTGIFPSNYVK 1056
Cdd:cd11873      1 EVIVEFDYDAEEPDELTLKVGDIITnVKKMEEGWWEGTLNGKRGMFPDNFVK 52

Src homology 3 domain of Blk Protein Tyrosine Kinase; Blk is a member of the Src subfamily of proteins, which are cytoplasmic (or non-receptor) PTKs. It is expressed specifically in B-cells and is involved in pre-BCR (B-cell receptor) signaling. Src kinases contain an N-terminal SH4 domain with a myristoylation site, followed by SH3 and SH2 domains, a tyr kinase domain, and a regulatory C-terminal region containing a conserved tyr. They are activated by autophosphorylation at the tyr kinase domain, but are negatively regulated by phosphorylation at the C-terminal tyr by Csk (C-terminal Src Kinase). The SH3 domain of Src kinases contributes to substrate recruitment by binding adaptor proteins/substrates, and regulation of kinase activity through an intramolecular interaction. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212942 [Multi-domain] Cd Length: 54 Bit Score: 52.13 E-value: 1.76e-08

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|..
gi 1804876928 1153 VIAMYDYVANNEDELNFSKGQLINVLnKDDPDWWQGE--INGVTGLFPSNYV 1202
Cdd:cd12009      2 VIAQYDFVPSNERDLQLKKGEKLQVL-KSDGEWWLAKslTTGKEGYIPSNYV 52

Src Homology 3 domain of Mixed Lineage Kinases 1, 2, and 3; MLKs 1, 2, and 3 are Serine/Threonine Kinases (STKs), catalyzing the transfer of the gamma-phosphoryl group from ATP to S/T residues on protein substrates. MLKs act as mitogen-activated protein kinase kinase kinases (MAP3Ks, MKKKs, MAPKKKs), which phosphorylate and activate MAPK kinases (MAPKKs or MKKs or MAP2Ks), which in turn phosphorylate and activate MAPKs during signaling cascades that are important in mediating cellular responses to extracellular signals. MLKs play roles in immunity and inflammation, as well as in cell death, proliferation, and cell cycle regulation. Little is known about the specific function of MLK1, also called MAP3K9. It is capable of activating the c-Jun N-terminal kinase pathway. Mice lacking both MLK1 and MLK2 are viable, fertile, and have normal life spans. MLK2, also called MAP3K10, is abundant in brain, skeletal muscle, and testis. It functions upstream of the MAPK, c-Jun N-terminal kinase. It binds hippocalcin, a calcium-sensor protein that protects neurons against calcium-induced cell death. Both MLK2 and hippocalcin may be associated with the pathogenesis of Parkinson's disease. MLK3, also called MAP3K11, is highly expressed in breast cancer cells and its signaling through c-Jun N-terminal kinase has been implicated in the migration, invasion, and malignancy of cancer cells. It also functions as a negative regulator of Inhibitor of Nuclear Factor-KappaB Kinase (IKK) and thus, impacts inflammation and immunity. MLKs contain an SH3 domain, a catalytic kinase domain, a leucine zipper, a proline-rich region, and a CRIB domain that mediates binding to GTP-bound Cdc42 and Rac. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212992 [Multi-domain] Cd Length: 58 Bit Score: 52.46 E-value: 1.76e-08

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....*..
gi 1804876928 1007 YIALYSYSSVEPGDLTFIEGEEILVTQKDGE------WWTGSIGDRTGIFPSNYVKP 1057
Cdd:cd12059      2 WTAVFDYEASAEDELTLRRGDRVEVLSKDSAvsgdegWWTGKINDRVGIFPSNYVTS 58

C-terminal Src homology 3 domain of GRB2-related adaptor protein; GRAP is a GRB-2 like adaptor protein that is highly expressed in lymphoid tissues. It acts as a negative regulator of T cell receptor (TCR)-induced lymphocyte proliferation by downregulating the signaling to the Ras/ERK pathway. It has been identified as a regulator of TGFbeta signaling in diabetic kidney tubules and may have a role in the pathogenesis of the disease. GRAP contains an N-terminal SH3 domain, a central SH2 domain, and a C-terminal SH3 domain. The C-terminal SH3 domains (SH3c) of the related proteins, GRB2 and GRAP2, have been shown to bind to classical PxxP motif ligands, as well as to non-classical motifs. GRB2 SH3c binds Gab2 (Grb2-associated binder 2) through epitopes containing RxxK motifs, while the SH3c of GRAP2 binds to the phosphatase-like protein HD-PTP via a RxxxxK motif. SH3 domains are protein interaction domains that typically bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212884 Cd Length: 53 Bit Score: 52.11 E-value: 1.80e-08

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|
gi 1804876928 1009 ALYSYSSVEPGDLTFIEGEEILVTQK-DGEWWTGSIGDRTGIFPSNYVKP 1057
Cdd:cd11951      4 AQYDFSAEDPSQLSFRRGDIIEVLDCpDPNWWRGRISGRVGFFPRNYVHP 53

C-terminal (or second) Src homology 3 domain of VAV2 protein; VAV2 is widely expressed and functions as a guanine nucleotide exchange factor (GEF) for RhoA, RhoB and RhoG and also activates Rac1 and Cdc42. It is implicated in many cellular and physiological functions including blood pressure control, eye development, neurite outgrowth and branching, EGFR endocytosis and degradation, and cell cluster morphology, among others. It has been reported to associate with Nek3. VAV proteins contain several domains that enable their function: N-terminal calponin homology (CH), acidic, RhoGEF (also called Dbl-homologous or DH), Pleckstrin Homology (PH), C1 (zinc finger), SH2, and two SH3 domains. The SH3 domain of VAV is involved in the localization of proteins to specific sites within the cell, by interacting with proline-rich sequences within target proteins. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212910 [Multi-domain] Cd Length: 58 Bit Score: 52.32 E-value: 1.81e-08

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|..
gi 1804876928  787 ALYRFEARSHDEMSFNSGDIIQVDEKTIGEPGWLYGSFQGNFGWFPCNYVEK 838
Cdd:cd11977      5 ARYNFAARDMRELSLREGDVVRIYSRIGGDQGWWKGETNGRIGWFPSTYVEE 56

helix-rich Mycoplasma protein; Members of this family occur strictly within a subset of Mycoplasma species. Members average 750 amino acids in length, including signal peptide. Sequences are predicted (Jpred 3) to be almost entirely alpha-helical. These sequences show strong periodicity (consistent with long alpha helical structures) and low complexity rich in D,E,N,Q, and K. Genes encoding these proteins are often found in tandem. The function is unknown.

Pssm-ID: 275316 [Multi-domain] Cd Length: 745 Bit Score: 59.26 E-value: 1.85e-08

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1804876928  435 KEKEEWERKQRELQEQEWKKQLELEKRLEKQRELERQREEERRKEIERREAAKQ--ELERQRrlewerirrQELLNQRNR 512
Cdd:TIGR04523  166 KQKEELENELNLLEKEKLNIQKNIDKIKNKLLKLELLLSNLKKKIQKNKSLESQisELKKQN---------NQLKDNIEK 236

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1804876928  513 EQEEIVRLNSKKKSLHLELEALNGKHQQISGRLQD------------VRLRKQTQ--KTEIEVLDKQCDLEIMeiKQLQQ 578
Cdd:TIGR04523  237 KQQEINEKTTEISNTQTQLNQLKDEQNKIKKQLSEkqkeleqnnkkiKELEKQLNqlKSEISDLNNQKEQDWN--KELKS 314

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1804876928  579 ELQDYQNKLIYLvpEKQLLNERIKNMQLGNT-PDLGIDLLHKKSlEKEELCQRLKE---QLDALEKETASKLSEMDS--- 651
Cdd:TIGR04523  315 ELKNQEKKLEEI--QNQISQNNKIISQLNEQiSQLKKELTNSES-ENSEKQRELEEkqnEIEKLKKENQSYKQEIKNles 391

                          250       260       270       280       290       300       310       320
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1804876928  652 --------FNNQLKCGNMDDSVLQCLLSLLSCLNNLFLLLKELRESYNTQQLALEQLHKIKRDKLKEIERKRSELIQK-K 722
Cdd:TIGR04523  392 qindleskIQNQEKLNQQKDEQIKKLQQEKELLEKEIERLKETIIKNNSEIKDLTNQDSVKELIIKNLDNTRESLETQlK 471

                          330       340       350       360       370
                   ....*....|....*....|....*....|....*....|....*....|...
gi 1804876928  723 KLEDEaIRKAKQGKENLWRESLRKEEEEKQkrLQEEKTQ--EKVQEEERKVEE 773
Cdd:TIGR04523  472 VLSRS-INKIKQNLEQKQKELKSKEKELKK--LNEEKKEleEKVKDLTKKISS 521

C-terminal Src homology 3 domain of Growth factor receptor-bound protein 2; GRB2 is a critical signaling molecule that regulates the Ras pathway by linking tyrosine kinases to the Ras guanine nucleotide releasing protein Sos (son of sevenless), which converts Ras to the active GTP-bound state. It is ubiquitously expressed in all tissues throughout development and is important in cell cycle progression, motility, morphogenesis, and angiogenesis. In lymphocytes, GRB2 is associated with antigen receptor signaling components. GRB2 contains an N-terminal SH3 domain, a central SH2 domain, and a C-terminal SH3 domain. The C-terminal SH3 domain of GRB2 binds to Gab2 (Grb2-associated binder 2) through epitopes containing RxxK motifs, as well as to the proline-rich C-terminus of FGRF2. SH3 domains are protein interaction domains that typically bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212882 [Multi-domain] Cd Length: 53 Bit Score: 52.15 E-value: 1.96e-08

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|
gi 1804876928 1009 ALYSYSSVEPGDLTFIEGEEI-LVTQKDGEWWTGSIGDRTGIFPSNYVKP 1057
Cdd:cd11949      4 ALFDFDPQEDGELGFRRGDFIeVMDNSDPNWWKGACHGQTGMFPRNYVTP 53

Third Src Homology 3 domain (SH3C) of CD2-associated protein and similar proteins; This subfamily is composed of the third SH3 domain (SH3C) of CD2AP, CIN85 (Cbl-interacting protein of 85 kDa), and similar domains. CD2AP and CIN85 are adaptor proteins that bind to protein partners and assemble complexes that have been implicated in T cell activation, kidney function, and apoptosis of neuronal cells. They also associate with endocytic proteins, actin cytoskeleton components, and other adaptor proteins involved in receptor tyrosine kinase (RTK) signaling. CD2AP and the main isoform of CIN85 contain three SH3 domains, a proline-rich region, and a C-terminal coiled-coil domain. All of these domains enable CD2AP and CIN85 to bind various protein partners and assemble complexes that have been implicated in many different functions. SH3C of both proteins have been shown to bind to ubiquitin. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212808 [Multi-domain] Cd Length: 55 Bit Score: 51.97 E-value: 1.98e-08

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|..
gi 1804876928 1009 ALYSYSSVEPGDLTFIEGEEILVTQKDGE---WWTGSIGDRTGIFPSNYVKP 1057
Cdd:cd11875      4 VLFDYEAENEDELTLREGDIVTILSKDCEdkgWWKGELNGKRGVFPDNFVEP 55

Src homology 3 domain of Blk Protein Tyrosine Kinase; Blk is a member of the Src subfamily of proteins, which are cytoplasmic (or non-receptor) PTKs. It is expressed specifically in B-cells and is involved in pre-BCR (B-cell receptor) signaling. Src kinases contain an N-terminal SH4 domain with a myristoylation site, followed by SH3 and SH2 domains, a tyr kinase domain, and a regulatory C-terminal region containing a conserved tyr. They are activated by autophosphorylation at the tyr kinase domain, but are negatively regulated by phosphorylation at the C-terminal tyr by Csk (C-terminal Src Kinase). The SH3 domain of Src kinases contributes to substrate recruitment by binding adaptor proteins/substrates, and regulation of kinase activity through an intramolecular interaction. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212942 [Multi-domain] Cd Length: 54 Bit Score: 52.13 E-value: 1.98e-08

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....*..
gi 1804876928 1007 YIALYSYSSVEPGDLTFIEGEEILVTQKDGEWW------TGsigdRTGIFPSNYVKP 1057
Cdd:cd12009      2 VIAQYDFVPSNERDLQLKKGEKLQVLKSDGEWWlaksltTG----KEGYIPSNYVAR 54

C-terminal (or second) Src homology 3 domain of VAV3 protein; VAV3 is ubiquitously expressed and functions as a phosphorylation-dependent guanine nucleotide exchange factor (GEF) for RhoA, RhoG, and Rac1. It has been implicated to function in the hematopoietic, bone, cerebellar, and cardiovascular systems. VAV3 is essential in axon guidance in neurons that control blood pressure and respiration. It is overexpressed in prostate cancer cells and it plays a role in regulating androgen receptor transcriptional activity. VAV proteins contain several domains that enable their function: N-terminal calponin homology (CH), acidic, RhoGEF (also called Dbl-homologous or DH), Pleckstrin Homology (PH), C1 (zinc finger), SH2, and two SH3 domains. The SH3 domain of VAV is involved in the localization of proteins to specific sites within the cell, by interacting with proline-rich sequences within target proteins. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212911 [Multi-domain] Cd Length: 56 Bit Score: 51.95 E-value: 2.05e-08

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|.
gi 1804876928 1154 IAMYDYVANNEDELNFSKGQLINVLNKDDPD-WWQGEINGVTGLFPSNYVK 1203
Cdd:cd11978      4 IARYDFCARDMRELSLLKGDVVKIYTKMSTNgWWRGEVNGRVGWFPSTYVE 54

Src homology 3 domain of High osmolarity signaling protein Sho1p; Sho1p (or Sho1), also called SSU81 (Suppressor of SUA8-1 mutation), is a yeast membrane protein that regulates adaptation to high salt conditions by activating the HOG (high-osmolarity glycerol) pathway. High salt concentrations lead to the localization to the membrane of the MAPKK Pbs2, which is then activated by the MAPKK Ste11 and in turn, activates the MAPK Hog1. Pbs2 is localized to the membrane though the interaction of its PxxP motif with the SH3 domain of Sho1p. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212789 [Multi-domain] Cd Length: 55 Bit Score: 52.04 E-value: 2.08e-08

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....
gi 1804876928 1155 AMYDYVANNED--ELNFSKGQLINVlnKDDP-DWWQGEI-NGVTGLFPSNYVKM 1204
Cdd:cd11855      4 ALYPYDASPDDpnELSFEKGEILEV--SDTSgKWWQARKsNGETGICPSNYLQL 55

Src homology 3 domain of Protein arginine N-methyltransferase 2; PRMT2, also called HRMT1L1, belongs to the arginine methyltransferase protein family. It functions as a coactivator to both estrogen receptor alpha (ER-alpha) and androgen receptor (AR), presumably through arginine methylation. The ER-alpha transcription factor is involved in cell proliferation, differentiation, morphogenesis, and apoptosis, and is also implicated in the development and progression of breast cancer. PRMT2 and its variants are upregulated in breast cancer cells and may be involved in modulating the ER-alpha signaling pathway during formation of breast cancer. PRMT2 also plays a role in regulating the function of E2F transcription factors, which are critical cell cycle regulators, by binding to the retinoblastoma gene product (RB). It contains an N-terminal SH3 domain and an AdoMet binding domain. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212740 [Multi-domain] Cd Length: 53 Bit Score: 52.01 E-value: 2.10e-08

                           10        20        30        40
                   ....*....|....*....|....*....|....*....|....*....
gi 1804876928 1085 YVASGSEQLSLAPGQLILILKKNSSGWWQGELQArgkkrQKGWFPASHV 1133
Cdd:cd11806      8 FVATDDSQLSFESGDKLLVLRKPSVDWWWAEHNG-----CCGYIPASHL 51

Src Homology 3 domain of Myosin XV; This subfamily is composed of proteins with similarity to Myosin XVa. Myosin XVa is an unconventional myosin that is critical for the normal growth of mechanosensory stereocilia of inner ear hair cells. Mutations in the myosin XVa gene are associated with nonsyndromic hearing loss. Myosin XVa contains a unique N-terminal extension followed by a motor domain, light chain-binding IQ motifs, and a tail consisting of a pair of MyTH4-FERM tandems separated by a SH3 domain, and a PDZ domain. SH3 domains bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs; they play a role in the regulation of enzymes by intramolecular interactions, changing the subcellular localization of signal pathway components and mediate multiprotein complex assemblies.

Pssm-ID: 212817 [Multi-domain] Cd Length: 56 Bit Score: 51.94 E-value: 2.35e-08

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|...
gi 1804876928 1153 VIAMYDYVANNEDELNFSKGQLINVLNK---DDPDWWQGEINGVTGLFPSNYV 1202
Cdd:cd11884      2 VVAVRAYITRDQTLLSFHKGDVIKLLPKegpLDPGWLFGTLDGRSGAFPKEYV 54

Src homology 3 domain of Signal Transducing Adaptor Molecule 2; STAM2, also called EAST (Epidermal growth factor receptor-associated protein with SH3 and TAM domain) or Hbp (Hrs binding protein), is part of the endosomal sorting complex required for transport (ESCRT-0). It plays a role in sorting mono-ubiquinated endosomal cargo for trafficking to the lysosome for degradation. It is also involved in the regulation of exocytosis. STAMs were discovered as proteins that are highly phosphorylated following cytokine and growth factor stimulation. They function in cytokine signaling and surface receptor degradation, as well as regulate Golgi morphology. They associate with many proteins including Jak2 and Jak3 tyrosine kinases, Hrs, AMSH, and UBPY. STAM adaptor proteins contain VHS (Vps27, Hrs, STAM homology), ubiquitin interacting (UIM), and SH3 domains. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212896 [Multi-domain] Cd Length: 57 Bit Score: 51.94 E-value: 2.50e-08

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|.
gi 1804876928  923 KAQALCSWTAKKDNHLNFSKHDIITVLEQQE-NWWFGEVHGGRGWFPKSYV 972
Cdd:cd11963      3 KVRALYDFEAVEDNELTFKHGEIIIVLDDSDaNWWKGENHRGVGLFPSNFV 53

SH3 domain; SH3 (Src homology 3) domains are often indicative of a protein involved in signal transduction related to cytoskeletal organization. First described in the Src cytoplasmic tyrosine kinase. The structure is a partly opened beta barrel.

Pssm-ID: 394975 [Multi-domain] Cd Length: 47 Bit Score: 51.44 E-value: 2.60e-08

                           10        20        30        40
                   ....*....|....*....|....*....|....*....|....*....
gi 1804876928  786 KALYRFEARSHDEMSFNSGDIIQVDEKTigEPGWLYG-SFQGNFGWFPC 833
Cdd:pfam00018    1 VALYDYTAQEPDELSFKKGDIIIVLEKS--EDGWWKGrNKGGKEGLIPS 47

Third Src Homology 3 domain of Nck2 adaptor protein; Nck2 (also called Nckbeta or Growth factor receptor-bound protein 4, Grb4) plays a crucial role in connecting signaling pathways of tyrosine kinase receptors and important effectors in actin dynamics and cytoskeletal remodeling. It binds neuronal signaling proteins such as ephrinB and Disabled-1 (Dab-1) exclusively. Nck adaptor proteins regulate actin cytoskeleton dynamics by linking proline-rich effector molecules to protein tyrosine kinases and phosphorylated signaling intermediates. They contain three SH3 domains and a C-terminal SH2 domain. They function downstream of the PDGFbeta receptor and are involved in Rho GTPase signaling and actin dynamics. Vertebrates contain two Nck adaptor proteins: Nck1 (also called Nckalpha) and Nck2, which show partly overlapping functions but also bind distinct targets. The third SH3 domain of Nck appears to prefer ligands with a PxAPxR motif. SH3 domains are protein interaction domains that usually bind to proline-rich ligands with moderate affinity and selectivity, preferentially a PxxP motif. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212836 [Multi-domain] Cd Length: 59 Bit Score: 51.98 E-value: 2.61e-08

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|...
gi 1804876928 1153 VIAMYDYVANNEDELNFSKGQLINVLNK--DDPDWWQGE-INGVTGLFPSNYV 1202
Cdd:cd11903      3 VQTLYPFSSVTEEELNFEKGETMEVIEKpeNDPEWWKCKnSRGQVGLVPKNYV 55

Src homology 3 domain of Alpha Spectrin; Spectrin is a major structural component of the red blood cell membrane skeleton and is important in erythropoiesis and membrane biogenesis. It is a flexible, rope-like molecule composed of two subunits, alpha and beta, which consist of many spectrin-type repeats. Alpha and beta spectrin associate to form heterodimers and tetramers; spectrin tetramer formation is critical for red cell shape and deformability. Defects in alpha spectrin have been associated with inherited hemolytic anemias including hereditary spherocytosis (HSp), hereditary elliptocytosis (HE), and hereditary pyropoikilocytosis (HPP). Alpha spectrin contains a middle SH3 domain and a C-terminal EF-hand binding motif in addition to multiple spectrin repeats. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212742 [Multi-domain] Cd Length: 53 Bit Score: 51.72 E-value: 2.66e-08

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|.
gi 1804876928 1153 VIAMYDYVANNEDELNFSKGQLINVLNKDDPDWWQGEINGVTGLFPSNYVK 1203
Cdd:cd11808      2 VVALYDYQEKSPREVSMKKGDILTLLNSSNKDWWKVEVNDRQGFVPAAYVK 52

Src Homology 3 domain of Cytokinesis protein 3 and similar proteins; Cytokinesis protein 3 (Cyk3 or Cyk3p) is a component of the actomyosin ring independent cytokinesis pathway in yeast. It interacts with Inn1 and facilitates its recruitment to the bud neck, thereby promoting cytokinesis. Cyk3p contains an N-terminal SH3 domain and a C-terminal transglutaminase-like domain. The Cyk3p SH3 domain binds to the C-terminal proline-rich region of Inn1. SH3 domains bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs; they play a role in the regulation of enzymes by intramolecular interactions, changing the subcellular localization of signal pathway components and mediate multiprotein complex assemblies.

Pssm-ID: 212822 Cd Length: 53 Bit Score: 51.73 E-value: 2.69e-08

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|
gi 1804876928 1009 ALYSYSSVEPGDLTFIEGEEILVTQ-KDGEWWTGS-IGDRT-GIFPSNYV 1055
Cdd:cd11889      4 AVYSWAGETEGDLGFLEGDLIEVLSiGDGSWWSGKlRRNGAeGIFPSNFV 53

Second C-terminal Src homology 3 domain of Fungal Actin-binding protein 1; Abp1 is an adaptor protein that functions in receptor-mediated endocytosis and vesicle trafficking. It contains an N-terminal actin-binding module, the actin-depolymerizing factor (ADF) homology domain, a central proline-rich region, and a C-terminal SH3 domain (many yeast Abp1 proteins contain two C-terminal SH3 domains). Yeast Abp1 also contains two acidic domains that bind directly to the Arp2/3 complex, which is required to initiate actin polymerization. The SH3 domain of yeast Abp1 binds and localizes the kinases, Ark1p and Prk1p, which facilitate actin patch disassembly following vesicle internalization. It also mediates the localization to the actin patch of the synaptojanin-like protein, Sjl2p, which plays a key role in endocytosis. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212894 [Multi-domain] Cd Length: 53 Bit Score: 51.76 E-value: 2.80e-08

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|.
gi 1804876928  924 AQALCSWTAKKDNHLNFSKHDIITVLE-QQENWWFGEVHGGRGWFPKSYVK 973
Cdd:cd11961      2 AKALYDYDAAEDNELSFFENDKIINIEfVDDDWWLGECHGSRGLFPSNYVE 52

Src Homology 3 domain of SH3 domain-containing protein 21 (SH3D21) and similar proteins; N-terminal SH3 domain of the uncharacterized protein SH3 domain-containing protein 21, and similar uncharacterized domains, it belongs to the CD2AP-like_3 subfamily of proteins. The CD2AP-like_3 subfamily is composed of the third SH3 domain (SH3C) of CD2AP, CIN85 (Cbl-interacting protein of 85 kDa), and similar domains. CD2AP and CIN85 are adaptor proteins that bind to protein partners and assemble complexes that have been implicated in T cell activation, kidney function, and apoptosis of neuronal cells. They also associate with endocytic proteins, actin cytoskeleton components, and other adaptor proteins involved in receptor tyrosine kinase (RTK) signaling. CD2AP and the main isoform of CIN85 contain three SH3 domains, a proline-rich region, and a C-terminal coiled-coil domain. All of these domains enable CD2AP and CIN85 to bind various protein partners and assemble complexes that have been implicated in many different functions. SH3C of both proteins have been shown to bind to ubiquitin. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 213018 [Multi-domain] Cd Length: 55 Bit Score: 51.70 E-value: 3.07e-08

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....*.
gi 1804876928 1080 QVTSAYVASGSEQLSLAPGQLILILKKNSS--GWWQGELQARgkkrqKGWFPASHV 1133
Cdd:cd12142      3 RVLFDYNPVAPDELALKKGDVIEVISKETEdeGWWEGELNGR-----RGFFPDNFV 53

Domain of unknown function (DUF4659); This family of proteins is found in eukaryotes. Proteins in this family are typically between 427 and 674 amino acids in length. There are two completely conserved residues (D and I) that may be functionally important.

Pssm-ID: 464768 [Multi-domain] Cd Length: 374 Bit Score: 57.74 E-value: 3.31e-08

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1804876928  415 EKRRQA-LMEQQQREAERKaQKEKEEWERKQRELQEQE-WKKQLELEKRL----EKQRELERQREEERRKEIERREAAKQ 488
Cdd:pfam15558   25 ELQQQAaLAWEELRRRDQK-RQETLERERRLLLQQSQEqWQAEKEQRKARlgreERRRADRREKQVIEKESRWREQAEDQ 103

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1804876928  489 ELERQRRLEWERI------RRQEllnQRNREQEEIvrLNSKKKSLHLEL-----EALNGKHQQISGRLQDVRLRKQTQKT 557
Cdd:pfam15558  104 ENQRQEKLERARQeaeqrkQCQE---QRLKEKEEE--LQALREQNSLQLqerleEACHKRQLKEREEQKKVQENNLSELL 178

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1804876928  558 EIEVLDKQCDL-----EIMEIKQLQQELQDYQNklIYlvpeKQLLNERIKNMQlgntpdlgidllhKKSLEKEELCQRLK 632
Cdd:pfam15558  179 NHQARKVLVDCqakaeELLRRLSLEQSLQRSQE--NY----EQLVEERHRELR-------------EKAQKEEEQFQRAK 239

                          250       260       270       280       290       300       310       320
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1804876928  633 EQLDALEKETASKLsemdsfnnqlkcgnmddSVLQcllsllsclnnlflLLKELResynTQQlALEQLHKIKRDK---LK 709
Cdd:pfam15558  240 WRAEEKEEERQEHK-----------------EALA--------------ELADRK----IQQ-ARQVAHKTVQDKaqrAR 283

                          330       340       350       360       370       380       390       400
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1804876928  710 E--IERKRSELIQKKKLEDEairkakqgkENLWRESLR---KEEEEKQKRLQEEKtqEKVQEEERKVEEkqcepASALVN 784
Cdd:pfam15558  284 ElnLEREKNHHILKLKVEKE---------EKCHREGIKeaiKKKEQRSEQISREK--EATLEEARKTAR-----ASFHMR 347

                          410
                   ....*....|....*..
gi 1804876928  785 YKALYRFEARSHDEMSF 801
Cdd:pfam15558  348 EKVREETNNRTFDKMAL 364

Src Homology 3 domain of the p40phox subunit of NADPH oxidase; p40phox, also called Neutrophil cytosol factor 4 (NCF-4), is a cytosolic subunit of the phagocytic NADPH oxidase complex (also called Nox2 or gp91phox) which plays a crucial role in the cellular response to bacterial infection. NADPH oxidase catalyzes the transfer of electrons from NADPH to oxygen during phagocytosis forming superoxide and reactive oxygen species. p40phox positively regulates NADPH oxidase in both phosphatidylinositol-3-phosphate (PI3P)-dependent and PI3P-independent manner. It contains an N-terminal PX domain, a central SH3 domain, and a C-terminal PB1 domain that interacts with p67phox. The SH3 domain of p40phox binds to canonical polyproline and noncanonical motifs at the C-terminus of p47phox. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212802 Cd Length: 54 Bit Score: 51.34 E-value: 3.86e-08

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|
gi 1804876928 1155 AMYDYVANNEDELNFSKGQLINVLNKDDPDWWQGEINGVTGLFPSNYVKM 1204
Cdd:cd11869      4 ALFDFTGNSKLELNFKAGDVIFLLSRVNKDWLEGTVRGATGIFPLSFVKI 53

Src homology 3 domain of Endophilin-A; Endophilins play roles in synaptic vesicle formation, virus budding, mitochondrial morphology maintenance, receptor-mediated endocytosis inhibition, and endosomal sorting. They are classified into two types, A and B. Vertebrates contain three endophilin-A isoforms (A1, A2, and A3). Endophilin-A proteins are enriched in the brain and play multiple roles in receptor-mediated endocytosis. They tubulate membranes and regulate calcium influx into neurons to trigger the activation of the endocytic machinery. They are also involved in the sorting of plasma membrane proteins, actin filament assembly, and the uncoating of clathrin-coated vesicles for fusion with endosomes. Endophilins contain an N-terminal N-BAR domain (BAR domain with an additional N-terminal amphipathic helix), followed by a variable region containing proline clusters, and a C-terminal SH3 domain. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212737 [Multi-domain] Cd Length: 55 Bit Score: 51.11 E-value: 4.14e-08

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|...
gi 1804876928  924 AQALCSWTAKKDNHLNFSKHDIITVLEQ-QENWWFGEVHGGRGWFPKSYVKII 975
Cdd:cd11803      3 CRALYDFEPENEGELGFKEGDIITLTNQiDENWYEGMVNGQSGFFPVNYVEVL 55

MAEBL; Provisional

Pssm-ID: 173412 [Multi-domain] Cd Length: 2084 Bit Score: 58.61 E-value: 4.24e-08

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1804876928  389 EEPQKKLpvtfEDKRKANYERGNVELEKRRQALMEQQQReaeRKAQKEKEEwERKQRELQE-QEWKKQLELEKRLEKQRE 467
Cdd:PTZ00121  1233 EEAKKDA----EEAKKAEEERNNEEIRKFEEARMAHFAR---RQAAIKAEE-ARKADELKKaEEKKKADEAKKAEEKKKA 1304

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1804876928  468 LErqreeerrkeierreaAKQELERQRRLEWERIRRQELLNQRNREQEEIVRLNSKKKSLHLELEALNGKHQQISGRLQD 547
Cdd:PTZ00121  1305 DE----------------AKKKAEEAKKADEAKKKAEEAKKKADAAKKKAEEAKKAAEAAKAEAEAAADEAEAAEEKAEA 1368

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1804876928  548 VRLRKQTQKTEIEVLDKQCD--LEIMEIKQLQQELQDYQNKLIYLVPEKQLLNERIKNMQLGNTPdlgiDLLHKKSLEKE 625
Cdd:PTZ00121  1369 AEKKKEEAKKKADAAKKKAEekKKADEAKKKAEEDKKKADELKKAAAAKKKADEAKKKAEEKKKA----DEAKKKAEEAK 1444

                          250       260       270       280       290       300       310       320
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1804876928  626 ELCQRLKEQLDALEKETASKLSEMDSFNNQLKCGNMDDSVLQCLLSLLSCLNNLFLLLKELRESYNTQQLALEQLHKIKR 705
Cdd:PTZ00121  1445 KADEAKKKAEEAKKAEEAKKKAEEAKKADEAKKKAEEAKKADEAKKKAEEAKKKADEAKKAAEAKKKADEAKKAEEAKKA 1524

                          330       340       350       360       370       380       390       400
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1804876928  706 DKLKEIERKRSELIQKKKledEAIRKAKQGKEnlwRESLRKEEEEK---QKRLQEEKTQEKVQ--EEERKVEEKQCEPAS 780
Cdd:PTZ00121  1525 DEAKKAEEAKKADEAKKA---EEKKKADELKK---AEELKKAEEKKkaeEAKKAEEDKNMALRkaEEAKKAEEARIEEVM 1598

                          410       420       430
                   ....*....|....*....|....*....|..
gi 1804876928  781 ALVNYKALYRFE-ARSHDEMSFNSGDIIQVDE 811
Cdd:PTZ00121  1599 KLYEEEKKMKAEeAKKAEEAKIKAEELKKAEE 1630

N-terminal Src Homology 3 domain of Ct10 Regulator of Kinase adaptor proteins; CRK adaptor proteins consists of SH2 and SH3 domains, which bind tyrosine-phosphorylated peptides and proline-rich motifs, respectively. They function downstream of protein tyrosine kinases in many signaling pathways started by various extracellular signals, including growth and differentiation factors. Cellular CRK (c-CRK) contains a single SH2 domain, followed by N-terminal and C-terminal SH3 domains. It is involved in the regulation of many cellular processes including cell growth, motility, adhesion, and apoptosis. CRK has been implicated in the malignancy of various human cancers. The N-terminal SH3 domain of CRK binds a number of target proteins including DOCK180, C3G, SOS, and cABL. The CRK family includes two alternatively spliced protein forms, CRKI and CRKII, that are expressed by the CRK gene, and the CRK-like (CRKL) protein, which is expressed by a distinct gene (CRKL). SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212692 [Multi-domain] Cd Length: 55 Bit Score: 51.21 E-value: 4.56e-08

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|.
gi 1804876928 1153 VIAMYDYVANNEDELNFSKGQLINVLNKDDPDWWQGE-INGVTGLFPSNYV 1202
Cdd:cd11758      3 VRALFDFPGNDDEDLPFKKGEILTVIRKPEEQWWNARnSEGKTGMIPVPYV 53

Variant SH3 domain; SH3 (Src homology 3) domains are often indicative of a protein involved in signal transduction related to cytoskeletal organization. First described in the Src cytoplasmic tyrosine kinase. The structure is a partly opened beta barrel.

Pssm-ID: 429575 [Multi-domain] Cd Length: 54 Bit Score: 51.06 E-value: 4.83e-08

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|..
gi 1804876928 1007 YIALYSYSSVEPGDLTFIEGEEILVTQKD-GEWWTGSIGDRTGIFPSNYVKP 1057
Cdd:pfam07653    2 GRVIFDYVGTDKNGLTLKKGDVVKVLGKDnDGWWEGETGGRVGLVPSTAVEE 53

C-terminal Src Homology 3 domain of the p67phox subunit of NADPH oxidase and similar proteins; This subfamily is composed of p67phox, NADPH oxidase activator 1 (Noxa1), and similar proteins. p67phox, also called Neutrophil cytosol factor 2 (NCF-2), and Noxa1 are homologs and are the cytosolic subunits of the phagocytic (Nox2) and nonphagocytic (Nox1) NADPH oxidase complexes, respectively. NADPH oxidase catalyzes the transfer of electrons from NADPH to oxygen during phagocytosis forming superoxide and reactive oxygen species. p67phox and Noxa1 play regulatory roles. p67phox contains N-terminal TPR, first SH3 (or N-terminal or central SH3), PB1, and C-terminal SH3 domains. Noxa1 has a similar domain architecture except it is lacking the N-terminal SH3 domain. The TPR domain of both binds activated GTP-bound Rac, while the C-terminal SH3 domain of p67phox and Noxa1 binds the polyproline motif found at the C-terminus of p47phox and Noxo1, respectively. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212803 [Multi-domain] Cd Length: 53 Bit Score: 50.99 E-value: 5.02e-08

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|.
gi 1804876928 1008 IALYSYSSVEPGDLTFIEGEEILV-TQKDGEWWTGSIGDRTGIFPSNYVKP 1057
Cdd:cd11870      3 VALHRYEAQGPEDLGFREGDTIDVlSEVNEAWLEGHSDGRVGIFPKCFVVP 53

Src homology 3 domain of Signal Transducing Adaptor Molecule 2; STAM2, also called EAST (Epidermal growth factor receptor-associated protein with SH3 and TAM domain) or Hbp (Hrs binding protein), is part of the endosomal sorting complex required for transport (ESCRT-0). It plays a role in sorting mono-ubiquinated endosomal cargo for trafficking to the lysosome for degradation. It is also involved in the regulation of exocytosis. STAMs were discovered as proteins that are highly phosphorylated following cytokine and growth factor stimulation. They function in cytokine signaling and surface receptor degradation, as well as regulate Golgi morphology. They associate with many proteins including Jak2 and Jak3 tyrosine kinases, Hrs, AMSH, and UBPY. STAM adaptor proteins contain VHS (Vps27, Hrs, STAM homology), ubiquitin interacting (UIM), and SH3 domains. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212896 [Multi-domain] Cd Length: 57 Bit Score: 51.17 E-value: 5.10e-08

                           10        20        30        40
                   ....*....|....*....|....*....|....*....|....*...
gi 1804876928 1009 ALYSYSSVEPGDLTFIEGEEILV-TQKDGEWWTGSIGDRTGIFPSNYV 1055
Cdd:cd11963      6 ALYDFEAVEDNELTFKHGEIIIVlDDSDANWWKGENHRGVGLFPSNFV 53

Src Homology 3 domain of Amphiphysin and related domains; Amphiphysins function primarily in endocytosis and other membrane remodeling events. They exist in several isoforms and mammals possess two amphiphysin proteins from distinct genes. Amphiphysin I proteins, enriched in the brain and nervous system, contain domains that bind clathrin, Adaptor Protein complex 2 (AP2), dynamin, and synaptojanin. They function in synaptic vesicle endocytosis. Human autoantibodies to amphiphysin I hinder GABAergic signaling and contribute to the pathogenesis of paraneoplastic stiff-person syndrome. Some amphiphysin II isoforms, also called Bridging integrator 1 (Bin1), are localized in many different tissues and may function in intracellular vesicle trafficking. In skeletal muscle, Bin1 plays a role in the organization and maintenance of the T-tubule network. Mutations in Bin1 are associated with autosomal recessive centronuclear myopathy. Amphiphysins contain an N-terminal BAR domain with an additional N-terminal amphipathic helix (an N-BAR), a variable central domain, and a C-terminal SH3 domain. The SH3 domain of amphiphysins bind proline-rich motifs present in binding partners such as dynamin, synaptojanin, and nsP3. It also belongs to a subset of SH3 domains that bind ubiquitin in a site that overlaps with the peptide binding site. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212724 [Multi-domain] Cd Length: 64 Bit Score: 51.17 E-value: 5.37e-08

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....*...
gi 1804876928 1153 VIAMYDYVANNEDELNFSKGQLINVLNKDDPD-----WWQG--EINGVTGLFPSNYVK 1203
Cdd:cd11790      5 VRATHDYTAEDTDELTFEKGDVILVIPFDDPEeqdegWLMGvkESTGCRGVFPENFTE 62

Second Src Homology 3 domain of the fungal endocytic adaptor protein Sla1p; Sla1p facilitates endocytosis by playing a role as an adaptor protein in coupling components of the actin cytoskeleton to the endocytic machinery. It interacts with Abp1p, Las17p and Pan1p, which are activator proteins of actin-related protein 2/3 (Arp2/3). Sla1p contains multiple domains including three SH3 domains, a SAM (sterile alpha motif) domain, and a Sla1 homology domain 1 (SHD1), which binds to the NPFXD motif that is found in many integral membrane proteins such as the Golgi-localized Arf-binding protein Lsb5p and the P4-ATPases, Drs2p and Dnf1p. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212708 [Multi-domain] Cd Length: 52 Bit Score: 50.54 E-value: 5.64e-08

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|..
gi 1804876928 1152 QVIAMYDYVANNEDELNFSKGQLINVLNKDDPDWWQGEINGVT-GLFPSNYV 1202
Cdd:cd11774      1 QAKALYDYDKQTEEELSFNEGDTLDVYDDSDSDWILVGFNGTQfGFVPANYI 52

Src Homology 3 domain of Small G protein Signaling Modulator 3; SGSM3 is also called Merlin-associated protein (MAP), RUN and SH3 domain-containing protein (RUSC3), RUN and TBC1 domain-containing protein 3 (RUTBC3), Rab GTPase-activating protein 5 (RabGAP5), or Rab GAP-like protein (RabGAPLP). It is expressed ubiquitously and functions as a regulator of small G protein RAP- and RAB-mediated neuronal signaling. It is involved in modulating NGF-mediated neurite outgrowth and differentiation. It also interacts with the tumor suppressor merlin and may play a role in the merlin-associated suppression of cell growth. SGSM3 contains TBC, SH3, and RUN domains. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212747 Cd Length: 53 Bit Score: 50.58 E-value: 5.94e-08

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|
gi 1804876928 1155 AMYDYVANNEDELNFSKGQLINVLNKDDPDWWQGEINGVTGLFPSNYVKM 1204
Cdd:cd11813      4 ALLDFERHDDDELGFRKNDIITIISQKDEHCWVGELNGLRGWFPAKFVEL 53

Src homology 3 domain of Cortactin and related proteins; This subfamily includes cortactin, Abp1 (actin-binding protein 1), hematopoietic lineage cell-specific protein 1 (HS1), and similar proteins. These proteins are involved in regulating actin dynamics through direct or indirect interaction with the Arp2/3 complex, which is required to initiate actin polymerization. They all contain at least one C-terminal SH3 domain. Cortactin and HS1 bind Arp2/3 and actin through an N-terminal region that contains an acidic domain and several copies of a repeat domain found in cortactin and HS1. Abp1 binds actin via an N-terminal actin-depolymerizing factor (ADF) homology domain. Yeast Abp1 binds Arp2/3 directly through two acidic domains. Mammalian Abp1 does not directly interact with Arp2/3; instead, it regulates actin dynamics indirectly by interacting with dynamin and WASP family proteins. The C-terminal region of these proteins acts as an adaptor or scaffold that can connect membrane trafficking and signaling proteins that bind the SH3 domain within the actin network. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212753 [Multi-domain] Cd Length: 54 Bit Score: 50.77 E-value: 6.22e-08

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|.
gi 1804876928 1008 IALYSYSSVEPGDLTFIEGEEIL-VTQKDGEWWTGSIGD-RTGIFPSNYVK 1056
Cdd:cd11819      3 KALYDYQAAEDNEISFVEGDIITqIEQIDEGWWLGVNAKgQKGLFPANYVE 53

Myosin tail; The myosin molecule is a multi-subunit complex made up of two heavy chains and four light chains it is a fundamental contractile protein found in all eukaryote cell types. This family consists of the coiled-coil myosin heavy chain tail region. The coiled-coil is composed of the tail from two molecules of myosin. These can then assemble into the macromolecular thick filament. The coiled-coil region provides the structural backbone the thick filament.

Pssm-ID: 460256 [Multi-domain] Cd Length: 1081 Bit Score: 57.88 E-value: 6.29e-08

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1804876928  385 KIQEEEPQKKLPVTfEDKR----------KANYER---GNVEL--EKRRQALmeQQQREAErkaqKEKEEwERKQRElQE 449
Cdd:pfam01576  698 KTQLEELEDELQAT-EDAKlrlevnmqalKAQFERdlqARDEQgeEKRRQLV--KQVRELE----AELED-ERKQRA-QA 768

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1804876928  450 QEWKKQLELE-KRLEKQRELERQREEERRKEIERREAAKQELerQRRLEWERIRRQELLNQrNREQEeivrlnskKKSLH 528
Cdd:pfam01576  769 VAAKKKLELDlKELEAQIDAANKGREEAVKQLKKLQAQMKDL--QRELEEARASRDEILAQ-SKESE--------KKLKN 837

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1804876928  529 LELEALngkhqQISGRLQDV-RLRKQTQKTEIE--------------VLDKQCDLEiMEIKQLQQELQDYQNKLiylvpe 593
Cdd:pfam01576  838 LEAELL-----QLQEDLAASeRARRQAQQERDEladeiasgasgksaLQDEKRRLE-ARIAQLEEELEEEQSNT------ 905

                          250       260       270       280       290       300       310       320
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1804876928  594 kQLLNERIKNMQLgNTPDLGIDLLHKKSLekeelCQRL---KEQLDALEKETASKLSEMDSfnnqlkcgnmddSVLQCLL 670
Cdd:pfam01576  906 -ELLNDRLRKSTL-QVEQLTTELAAERST-----SQKSesaRQQLERQNKELKAKLQEMEG------------TVKSKFK 966

                          330       340       350       360       370       380       390       400
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1804876928  671 SLLSCLNNLFLLLKELRESYNTQQLALEQLHKIKRDKLKEIerkrseLIQkkkLEDEAiRKAKQGKENLWRESLRKeeee 750
Cdd:pfam01576  967 SSIAALEAKIAQLEEQLEQESRERQAANKLVRRTEKKLKEV------LLQ---VEDER-RHADQYKDQAEKGNSRM---- 1032

                          410
                   ....*....|....*
gi 1804876928  751 KQKRLQEEKTQEKVQ 765
Cdd:pfam01576 1033 KQLKRQLEEAEEEAS 1047

Src homology 3 domain of CAS (Crk-Associated Substrate) scaffolding proteins; CAS proteins function as molecular scaffolds to regulate protein complexes that are involved in many cellular processes including migration, chemotaxis, apoptosis, differentiation, and progenitor cell function. They mediate the signaling of integrins at focal adhesions where they localize, and thus, regulate cell invasion and survival. Over-expression of these proteins is implicated in poor prognosis, increased metastasis, and resistance to chemotherapeutics in many cancers such as breast, lung, melanoma, and glioblastoma. CAS proteins have also been linked to the pathogenesis of inflammatory disorders, Alzheimer's, Parkinson's, and developmental defects. They share a common domain structure that includes an N-terminal SH3 domain, an unstructured substrate domain that contains many YxxP motifs, a serine-rich four-helix bundle, and a FAT-like C-terminal domain. Vertebrates contain four CAS proteins: BCAR1 (or p130Cas), NEDD9 (or HEF1), EFS (or SIN), and CASS4 (or HEPL). The SH3 domain of CAS proteins binds to diverse partners including FAK, FRNK, Pyk2, PTP-PEST, DOCK180, among others. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212778 Cd Length: 56 Bit Score: 50.81 E-value: 6.60e-08

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|...
gi 1804876928 1155 AMYDYVANNEDELNFSKGQLINVLNKDDPD---WWQGEINGVTGLFPSNYVKM 1204
Cdd:cd11844      4 ALYDNVAESPDELAFRRGDILTVLEQNTAGlegWWLCSLRGRQGIAPGNRLKL 56

Src homology 3 domain of SH3 protein interacting with Nck, 90 kDa (SPIN90); SPIN90 is also called NCK interacting protein with SH3 domain (NCKIPSD), Dia-interacting protein (DIP), 54 kDa vimentin-interacting protein (VIP54), or WASP-interacting SH3-domain protein (WISH). It is an F-actin binding protein that regulates actin polymerization and endocytosis. It associates with the Arp2/3 complex near actin filaments and determines filament localization at the leading edge of lamellipodia. SPIN90 is expressed in the early stages of neuronal differentiation and plays a role in regulating growth cone dynamics and neurite outgrowth. It also interacts with IRSp53 and regulates cell motility by playing a role in the formation of membrane protrusions. SPIN90 contains an N-terminal SH3 domain, a proline-rich domain, and a C-terminal VCA (verprolin-homology and cofilin-like acidic) domain. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212783 [Multi-domain] Cd Length: 53 Bit Score: 50.39 E-value: 6.88e-08

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|..
gi 1804876928 1007 YIALYSYSSVEPGDLTFIEGEEILVTQK-DGEWW-TGSIGDRTGIFPSNYVK 1056
Cdd:cd11849      2 YRALYDFKSAEPNTLSFSEGETFLLLERsNAHWWlVTNHSGETGYVPANYVK 53

DNA double-strand break repair Rad50 ATPase;

Pssm-ID: 179385 [Multi-domain] Cd Length: 880 Bit Score: 57.74 E-value: 7.04e-08

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1804876928  400 EDKRKANYERGNVEL-----EKRRQALMEQQQ-----REAERKAQKEKEEWERKQRELQEQewkkQLELEKRLEKQRELE 469
Cdd:PRK02224   227 EQREQARETRDEADEvleehEERREELETLEAeiedlRETIAETEREREELAEEVRDLRER----LEELEEERDDLLAEA 302

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1804876928  470 RQREEERRKEIERREA-AKQELERQRRLEWERIRRQELLNQRNREQEEIVRLNSKKKSLHLELEALNGKhqqisgrLQDV 548
Cdd:PRK02224   303 GLDDADAEAVEARREElEDRDEELRDRLEECRVAAQAHNEEAESLREDADDLEERAEELREEAAELESE-------LEEA 375

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1804876928  549 RLRKQTQKTEIEVLDKQCDlEIME---------------IKQLQQELQDYQNKLIYLVPEKQLLNERI-KNMQL---GNT 609
Cdd:PRK02224   376 REAVEDRREEIEELEEEIE-ELRErfgdapvdlgnaedfLEELREERDELREREAELEATLRTARERVeEAEALleaGKC 454

                          250       260       270       280       290       300       310       320
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1804876928  610 PDLG--------IDLLHKKSLEKEELCQRL---KEQLDALEK--ETASKLSEMDSFNNQLKcGNMDDSVLqcllsllscl 676
Cdd:PRK02224   455 PECGqpvegsphVETIEEDRERVEELEAELedlEEEVEEVEErlERAEDLVEAEDRIERLE-ERREDLEE---------- 523

                          330       340       350       360       370       380       390       400
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1804876928  677 nnlflLLKELRESYNTQQLALEQLHKIK------------------------RDKLKEIERKRSELIQK----KKLED-- 726
Cdd:PRK02224   524 -----LIAERRETIEEKRERAEELRERAaeleaeaeekreaaaeaeeeaeeaREEVAELNSKLAELKERieslERIRTll 598

                          410       420       430       440       450       460       470
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 1804876928  727 EAI-------------RKAKQGKENLWRESL-----RKE-----------EEEKQKRLQEEKTQEKVQEEERKVEEK 774
Cdd:PRK02224   599 AAIadaedeierlrekREALAELNDERRERLaekreRKReleaefdeariEEAREDKERAEEYLEQVEEKLDELREE 675

Src Homology 3 domain of Abelson helper integration site-1 (AHI-1); AHI-1, also called Jouberin, is expressed in high levels in the brain, gonad tissues, and skeletal muscle. It is an adaptor protein that interacts with the small GTPase Rab8a and regulates it distribution and function, affecting cilium formation and vesicle transport. Mutations in the AHI-1 gene can cause Joubert syndrome, a disorder characterized by brainstem malformations, cerebellar aplasia/hypoplasia, and retinal dystrophy. AHI-1 variation is also associated with susceptibility to schizophrenia and type 2 diabetes mellitus progression. AHI-1 contains WD40 and SH3 domains. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212746 [Multi-domain] Cd Length: 52 Bit Score: 50.59 E-value: 7.05e-08

                           10        20        30        40
                   ....*....|....*....|....*....|....*....|....*....
gi 1804876928  926 ALCSWTAKKDNHLNFSKHDIITVLEQ-QENWWFGE-VHGGRGWFPKSYV 972
Cdd:cd11812      4 ALYDYTANRSDELTIHRGDIIRVLYKdNDNWWFGSlVNGQQGYFPANYV 52

Src homology 3 domains of the p47phox subunit of NADPH oxidase and similar domains; This family is composed of the tandem SH3 domains of p47phox subunit of NADPH oxidase and Nox Organizing protein 1 (NoxO1), the four SH3 domains of Tks4 (Tyr kinase substrate with four SH3 domains), the five SH3 domains of Tks5, the SH3 domain of obscurin, Myosin-I, and similar domains. Most members of this group also contain Phox homology (PX) domains, except for obscurin and Myosin-I. p47phox and NoxO1 are regulators of the phagocytic NADPH oxidase complex (also called Nox2 or gp91phox) and nonphagocytic NADPH oxidase Nox1, respectively. They play roles in the activation of their respective NADPH oxidase, which catalyzes the transfer of electrons from NADPH to molecular oxygen to form superoxide. Tks proteins are Src substrates and scaffolding proteins that play important roles in the formation of podosomes and invadopodia, the dynamic actin-rich structures that are related to cell migration and cancer cell invasion. Obscurin is a giant muscle protein that plays important roles in the organization and assembly of the myofibril and the sarcoplasmic reticulum. Type I myosins (Myosin-I) are actin-dependent motors in endocytic actin structures and actin patches. They play roles in membrane traffic in endocytic and secretory pathways, cell motility, and mechanosensing. Myosin-I contains an N-terminal actin-activated ATPase, a phospholipid-binding TH1 (tail homology 1) domain, and a C-terminal extension which includes an F-actin-binding TH2 domain, an SH3 domain, and an acidic peptide that participates in activating the Arp2/3complex. The SH3 domain of myosin-I is required for myosin-I-induced actin polymerization. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212790 [Multi-domain] Cd Length: 53 Bit Score: 50.33 E-value: 7.12e-08

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|...
gi 1804876928 1006 EYIALYSYSSVEPGDLTFIEGEEILVTQK-DGEWWTGSIGDRTGIFPSNYVKP 1057
Cdd:cd11856      1 SYVAIADYEAQGDDEISLQEGEVVEVLEKnDSGWWYVRKGDKEGWVPASYLEP 53

Src Homology 3 domain of Mixed Lineage Kinases; MLKs are Serine/Threonine Kinases (STKs), catalyzing the transfer of the gamma-phosphoryl group from ATP to S/T residues on protein substrates. MLKs act as mitogen-activated protein kinase kinase kinases (MAP3Ks, MKKKs, MAPKKKs), which phosphorylate and activate MAPK kinases (MAPKKs or MKKs or MAP2Ks), which in turn phosphorylate and activate MAPKs during signaling cascades that are important in mediating cellular responses to extracellular signals. MLKs play roles in immunity and inflammation, as well as in cell death, proliferation, and cell cycle regulation. Mammals have four MLKs (MLK1-4), mostly conserved in vertebrates, which contain an SH3 domain, a catalytic kinase domain, a leucine zipper, a proline-rich region, and a CRIB domain that mediates binding to GTP-bound Cdc42 and Rac. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212809 [Multi-domain] Cd Length: 58 Bit Score: 50.59 E-value: 7.17e-08

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|...
gi 1804876928  787 ALYRFEARSHDEMSFNSGDIIQV---DEKTIGEPGWLYGSFQGNFGWFPCNYV 836
Cdd:cd11876      4 ALFDYDARGEDELTLRRGQPVEVlskDAAVSGDEGWWTGKIGDKVGIFPSNYV 56

First C-terminal Src homology 3 domain of SH3 and cysteine-rich domain-containing (Stac) proteins; Stac proteins are putative adaptor proteins that contain a cysteine-rich C1 domain and one or two SH3 domains at the C-terminus. There are three mammalian members (Stac1, Stac2, and Stac3) of this family. Stac1 and Stac3 contain two SH3 domains while Stac2 contains a single SH3 domain at the C-terminus. This model represents the first C-terminal SH3 domain of Stac1 and Stac3, and the single C-terminal SH3 domain of Stac2. Stac1 and Stac2 have been found to be expressed differently in mature dorsal root ganglia (DRG) neurons. Stac1 is mainly expressed in peptidergic neurons while Stac2 is found in a subset of nonpeptidergic and all trkB+ neurons. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212767 [Multi-domain] Cd Length: 53 Bit Score: 50.58 E-value: 7.35e-08

                           10        20        30        40
                   ....*....|....*....|....*....|....*....|....*....
gi 1804876928 1154 IAMYDYVANNEDELNFSKGQLINVLNKDDPDWWQGEINGVTGLFPSNYV 1202
Cdd:cd11833      3 VALYKFKPQENEDLEMRPGDKITLLDDSNEDWWKGKIEDRVGFFPANFV 51

Src homology 3 domain of Signal Transducing Adaptor Molecules; STAMs were discovered as proteins that are highly phosphorylated following cytokine and growth factor stimulation. They function in cytokine signaling and surface receptor degradation, as well as regulate Golgi morphology. They associate with many proteins including Jak2 and Jak3 tyrosine kinases, Hrs, AMSH, and UBPY. STAM adaptor proteins contain VHS (Vps27, Hrs, STAM homology), ubiquitin interacting (UIM), and SH3 domains. There are two vertebrate STAMs, STAM1 and STAM2, which may be functionally redundant; vertebrate STAMs contain ITAM motifs. They are part of the endosomal sorting complex required for transport (ESCRT-0). STAM2 deficiency in mice did not cause any obvious abnormality, while STAM1 deficiency resulted in growth retardation. Loss of both STAM1 and STAM2 in mice proved lethal, indicating that STAMs are important for embryonic development. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212754 [Multi-domain] Cd Length: 54 Bit Score: 50.54 E-value: 7.44e-08

                           10        20        30        40
                   ....*....|....*....|....*....|....*....|....*....
gi 1804876928 1009 ALYSYSSVEPGDLTFIEGEEILVTQ-KDGEWWTGSIGDRTGIFPSNYVK 1056
Cdd:cd11820      5 ALYDFEAAEDNELTFKAGEIITVLDdSDPNWWKGSNHRGEGLFPANFVT 53

First Src Homology 3 domain of SH3 domain containing ring finger 3, an E3 ubiquitin-protein ligase; SH3RF3 is also called POSH2 (Plenty of SH3s 2) or SH3MD4 (SH3 multiple domains protein 4). It is a scaffold protein with E3 ubiquitin-protein ligase activity. It was identified in the screen for interacting partners of p21-activated kinase 2 (PAK2). It may play a role in regulating JNK mediated apoptosis in certain conditions. It also interacts with GTP-loaded Rac1. SH3RF3 is highly homologous to SH3RF1; it also contains an N-terminal RING finger domain and four SH3 domains. This model represents the first SH3 domain, located at the N-terminal half, of SH3RF3. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212861 Cd Length: 54 Bit Score: 50.31 E-value: 7.92e-08

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|
gi 1804876928  925 QALCSWTAKKDNHLNFSKHDIITVLEQ-QENWWFGEVHGGRGWFPKSYVK 973
Cdd:cd11928      4 KALYSYEGKEPGDLKFNKGDIIILRRKvDENWYHGELNGCHGFLPASYIQ 53

Src homology 3 domain of Ysc84p and similar fungal proteins; This family is composed of the Saccharomyces cerevisiae proteins, Ysc84p (also called LAS17-binding protein 4, Lsb4p) and Lsb3p, and similar fungal proteins. They contain an N-terminal SYLF domain (also called DUF500) and a C-terminal SH3 domain. Ysc84p localizes to actin patches and plays an important in actin polymerization during endocytosis. The N-terminal domain of both Ysc84p and Lsb3p can bind and bundle actin filaments. A study of the yeast SH3 domain interactome predicts that the SH3 domains of Lsb3p and Lsb4p may function as molecular hubs for the assembly of endocytic complexes. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212776 [Multi-domain] Cd Length: 55 Bit Score: 50.50 E-value: 7.94e-08

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|.
gi 1804876928  787 ALYRFEARSHDEMSFNSGDIIQVDEKTIGEPGWLYGSFQGNFGWFPCNYVE 837
Cdd:cd11842      4 ALYDFAGEQPGDLAFQKGDIITILKKSDSQNDWWTGRIGGREGIFPANYVE 54

Fifth Src homology 3 domain (or SH3E) of Intersectin-1; Intersectin-1 (ITSN1) is an adaptor protein that functions in exo- and endocytosis, actin cytoskeletal reorganization, and signal transduction. It plays a role in clathrin-coated pit (CCP) formation. It binds to many proteins through its multidomain structure and facilitate the assembly of multimeric complexes. ITSN1 localizes in membranous organelles, CCPs, the Golgi complex, and may be involved in the cell membrane trafficking system. It exists in alternatively spliced short and long isoforms. The short isoform contains two Eps15 homology domains (EH1 and EH2), a coiled-coil region and five SH3 domains (SH3A-E), while the long isoform, in addition, contains RhoGEF (also called Dbl-homologous or DH), Pleckstrin homology (PH) and C2 domains. The fifth SH3 domain (or SH3E) of ITSN1 has been shown to bind many protein partners including SGIP1, Sos1, dynamin1/2, CIN85, c-Cbl, SHIP2, N-WASP, and synaptojanin-1, among others. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212928 [Multi-domain] Cd Length: 54 Bit Score: 50.34 E-value: 7.98e-08

                           10        20        30        40
                   ....*....|....*....|....*....|....*....|....*.
gi 1804876928  930 WTAKKDNHLNFSKHDIITVLEQQE-NWWFGEVHGGRGWFPKSYVKI 974
Cdd:cd11995      9 YTAQNDDELAFSKGQIINVLNKEDpDWWKGELNGQVGLFPSNYVKL 54

C-terminal Src homology 3 domain of Growth factor receptor-bound protein 2 (GRB2) and related proteins; This family includes the adaptor protein GRB2 and related proteins including Drosophila melanogaster Downstream of receptor kinase (DRK), Caenorhabditis elegans Sex muscle abnormal protein 5 (Sem-5), GRB2-related adaptor protein (GRAP), GRAP2, and similar proteins. Family members contain an N-terminal SH3 domain, a central SH2 domain, and a C-terminal SH3 domain. GRB2/Sem-5/DRK is a critical signaling molecule that regulates the Ras pathway by linking tyrosine kinases to the Ras guanine nucleotide releasing protein Sos (son of sevenless), which converts Ras to the active GTP-bound state. GRAP2 plays an important role in T cell receptor (TCR) signaling by promoting the formation of the SLP-76:LAT complex, which couples the TCR to the Ras pathway. GRAP acts as a negative regulator of T cell receptor (TCR)-induced lymphocyte proliferation by downregulating the signaling to the Ras/ERK pathway. The C-terminal SH3 domains (SH3c) of GRB2 and GRAP2 have been shown to bind to classical PxxP motif ligands, as well as to non-classical motifs. GRB2 SH3c binds Gab2 (Grb2-associated binder 2) through epitopes containing RxxK motifs, while the SH3c of GRAP2 binds to the phosphatase-like protein HD-PTP via a RxxxxK motif. SH3 domains are protein interaction domains that typically bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212739 [Multi-domain] Cd Length: 53 Bit Score: 50.32 E-value: 8.14e-08

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|..
gi 1804876928  787 ALYRFEARSHDEMSFNSGDIIQVDEKTigEPGWLYGSFQGNFGWFPCNYVEK 838
Cdd:cd11805      4 ALYDFNPQEPGELEFRRGDIITVLDSS--DPDWWKGELRGRVGIFPANYVQP 53

Src homology 3 domains of the p47phox subunit of NADPH oxidase and similar domains; This family is composed of the tandem SH3 domains of p47phox subunit of NADPH oxidase and Nox Organizing protein 1 (NoxO1), the four SH3 domains of Tks4 (Tyr kinase substrate with four SH3 domains), the five SH3 domains of Tks5, the SH3 domain of obscurin, Myosin-I, and similar domains. Most members of this group also contain Phox homology (PX) domains, except for obscurin and Myosin-I. p47phox and NoxO1 are regulators of the phagocytic NADPH oxidase complex (also called Nox2 or gp91phox) and nonphagocytic NADPH oxidase Nox1, respectively. They play roles in the activation of their respective NADPH oxidase, which catalyzes the transfer of electrons from NADPH to molecular oxygen to form superoxide. Tks proteins are Src substrates and scaffolding proteins that play important roles in the formation of podosomes and invadopodia, the dynamic actin-rich structures that are related to cell migration and cancer cell invasion. Obscurin is a giant muscle protein that plays important roles in the organization and assembly of the myofibril and the sarcoplasmic reticulum. Type I myosins (Myosin-I) are actin-dependent motors in endocytic actin structures and actin patches. They play roles in membrane traffic in endocytic and secretory pathways, cell motility, and mechanosensing. Myosin-I contains an N-terminal actin-activated ATPase, a phospholipid-binding TH1 (tail homology 1) domain, and a C-terminal extension which includes an F-actin-binding TH2 domain, an SH3 domain, and an acidic peptide that participates in activating the Arp2/3complex. The SH3 domain of myosin-I is required for myosin-I-induced actin polymerization. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212790 [Multi-domain] Cd Length: 53 Bit Score: 50.33 E-value: 8.58e-08

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....
gi 1804876928  785 YKALYRFEARSHDEMSFNSGDIIQVDEKtiGEPGWLYGSFQGNFGWFPCNYVEK 838
Cdd:cd11856      2 YVAIADYEAQGDDEISLQEGEVVEVLEK--NDSGWWYVRKGDKEGWVPASYLEP 53

Src homology 3 domain of Lyn Protein Tyrosine Kinase; Lyn is a member of the Src subfamily of proteins, which are cytoplasmic (or non-receptor) PTKs. Lyn is expressed in B lymphocytes and myeloid cells. It exhibits both positive and negative regulatory roles in B cell receptor (BCR) signaling. Lyn, as well as Fyn and Blk, promotes B cell activation by phosphorylating ITAMs (immunoreceptor tyr activation motifs) in CD19 and in Ig components of BCR. It negatively regulates signaling by its unique ability to phosphorylate ITIMs (immunoreceptor tyr inhibition motifs) in cell surface receptors like CD22 and CD5. Lyn also plays an important role in G-CSF receptor signaling by phosphorylating a variety of adaptor molecules. Src kinases contain an N-terminal SH4 domain with a myristoylation site, followed by SH3 and SH2 domains, a tyr kinase domain, and a regulatory C-terminal region containing a conserved tyr. They are activated by autophosphorylation at the tyr kinase domain, but are negatively regulated by phosphorylation at the C-terminal tyr by Csk (C-terminal Src Kinase). The SH3 domain of Src kinases contributes to substrate recruitment by binding adaptor proteins/substrates, and regulation of kinase activity through an intramolecular interaction. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212937 [Multi-domain] Cd Length: 56 Bit Score: 50.38 E-value: 8.68e-08

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|
gi 1804876928 1008 IALYSYSSVEPGDLTFIEGEEILVTQKDGEWWTGS--IGDRTGIFPSNYV 1055
Cdd:cd12004      3 VALYPYDGIHEDDLSFKKGEKLKVIEEHGEWWKARslTTKKEGFIPSNYV 52

Src homology 3 domain of Nitric Oxide Synthase TRaffic INducer; Nostrin is expressed in endothelial and epithelial cells and is involved in the regulation, trafficking and targeting of endothelial NOS (eNOS). It facilitates the endocytosis of eNOS by coordinating the functions of dynamin and the Wiskott-Aldrich syndrome protein (WASP). Increased expression of Nostrin may be correlated to preeclampsia. Nostrin contains an N-terminal F-BAR domain and a C-terminal SH3 domain. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212757 [Multi-domain] Cd Length: 53 Bit Score: 50.03 E-value: 8.79e-08

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|
gi 1804876928 1084 AYVASGSEQLSLAPGQLILILKKNSSGWWQGELqaRGKkrqKGWFPASHV 1133
Cdd:cd11823      7 SYTANREDELSLQPGDIIEVHEKQDDGWWLGEL--NGK---KGIFPATYV 51

Src homology 3 domain of APC-Stimulated guanine nucleotide Exchange Factor 2; ASEF2, also called Spermatogenesis-associated protein 13 (SPATA13), is a GEF that localizes with actin at the leading edge of cells and is important in cell migration and adhesion dynamics. GEFs activate small GTPases by exchanging bound GDP for free GTP. ASEF2 can activate both Rac 1 and Cdc42, but only Rac1 activation is necessary for increased cell migration and adhesion turnover. Together with APC (adenomatous polyposis coli) and Neurabin2, a scaffold protein that binds F-actin, it is involved in regulating HGF-induced cell migration. ASEF2 contains a SH3 domain followed by RhoGEF (also called Dbl-homologous or DH) and Pleckstrin Homology (PH) domains. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212907 Cd Length: 54 Bit Score: 50.45 E-value: 8.82e-08

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|
gi 1804876928 1155 AMYDYVANNEDELNFSKGQLINVLNKDDPDWWQGEINGVTGLFPSNYVKM 1204
Cdd:cd11974      5 ALWDHVTMDDQELAFKAGDVIRVLEASNKDWWWGRNEDREAWFPASFVRL 54

Src Homology 3 domain of C-terminal Src kinase; CSK is a cytoplasmic (or nonreceptor) tyr kinase containing the Src homology domains, SH3 and SH2, N-terminal to the catalytic tyr kinase domain. They negatively regulate the activity of Src kinases that are anchored to the plasma membrane. To inhibit Src kinases, CSK is translocated to the membrane via binding to specific transmembrane proteins, G-proteins, or adaptor proteins near the membrane. CSK catalyzes the tyr phosphorylation of the regulatory C-terminal tail of Src kinases, resulting in their inactivation. It is expressed in a wide variety of tissues and plays a role, as a regulator of Src, in cell proliferation, survival, and differentiation, and consequently, in cancer development and progression. In addition, CSK also shows Src-independent functions. It is a critical component in G-protein signaling, and plays a role in cytoskeletal reorganization and cell migration. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212703 [Multi-domain] Cd Length: 57 Bit Score: 50.38 E-value: 9.54e-08

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....
gi 1804876928 1152 QVIAMYDYVANNEDELNFSKGQLINVLN-KDDPDWWQGE-INGVTGLFPSNYVK 1203
Cdd:cd11769      3 ECIAKYNFNGASEEDLPFKKGDILTIVAvTKDPNWYKAKnKDGREGMIPANYVQ 56

Second Src homology 3 domain (or SH3B) of Intersectin; Intersectins (ITSNs) are adaptor proteins that function in exo- and endocytosis, actin cytoskeletal reorganization, and signal transduction. They are essential for initiating clathrin-coated pit formation. They bind to many proteins through their multidomain structure and facilitate the assembly of multimeric complexes. Vertebrates contain two ITSN proteins, ITSN1 and ITSN2, which exist in alternatively spliced short and long isoforms. The short isoforms contain two Eps15 homology domains (EH1 and EH2), a coiled-coil region and five SH3 domains (SH3A-E), while the long isoforms, in addition, contain RhoGEF (also called Dbl-homologous or DH), Pleckstrin homology (PH) and C2 domains. ITSN1 and ITSN2 are both widely expressed, with variations depending on tissue type and stage of development. The second SH3 domain (or SH3B) of ITSN1 has been shown to bind WNK and CdGAP. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212771 [Multi-domain] Cd Length: 53 Bit Score: 50.06 E-value: 9.83e-08

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|..
gi 1804876928 1007 YIALYSYSSVEPGDLTFIEGEEILVTQKDGEWWTGSI-GDRTGIFPSNYVKP 1057
Cdd:cd11837      2 ATALYPWRAKKENHLSFAKGDIITVLEQQEMWWFGELeGGEEGWFPKSYVKE 53

Src homology 3 domain of ArfGAP with SH3 domain, ankyrin repeat and PH domain containing protein 1; ASAP1 is also called DDEF1 (Development and Differentiation Enhancing Factor 1), AMAP1, centaurin beta-4, or PAG2. an Arf GTPase activating protein (GAP) with activity towards Arf1 and Arf5 but not Arf6. However, it has been shown to bind GTP-Arf6 stably without GAP activity. It has been implicated in cell growth, migration, and survival, as well as in tumor invasion and malignancy. It binds paxillin and cortactin, two components of invadopodia which are essential for tumor invasiveness. It also binds focal adhesion kinase (FAK) and the SH2/SH3 adaptor CrkL. ASAP1 contains an N-terminal BAR domain, followed by a Pleckstrin homology (PH) domain, an Arf GAP domain, ankyrin (ANK) repeats, and a C-terminal SH3 domain. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212898 [Multi-domain] Cd Length: 57 Bit Score: 50.39 E-value: 9.92e-08

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....*.
gi 1804876928 1152 QVIAMYDYVANNEDELNFSKGQLINVLNKDDPDWWQGEINGV---TGLFPSNYVKM 1204
Cdd:cd11965      1 RVKTIYDCQADNDDELTFVEGEVIIVTGEEDQEWWIGHIEGQperKGVFPVSFVHI 56

First Src Homology 3 domain of SH3 domain containing ring finger 3, an E3 ubiquitin-protein ligase; SH3RF3 is also called POSH2 (Plenty of SH3s 2) or SH3MD4 (SH3 multiple domains protein 4). It is a scaffold protein with E3 ubiquitin-protein ligase activity. It was identified in the screen for interacting partners of p21-activated kinase 2 (PAK2). It may play a role in regulating JNK mediated apoptosis in certain conditions. It also interacts with GTP-loaded Rac1. SH3RF3 is highly homologous to SH3RF1; it also contains an N-terminal RING finger domain and four SH3 domains. This model represents the first SH3 domain, located at the N-terminal half, of SH3RF3. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212861 Cd Length: 54 Bit Score: 49.92 E-value: 1.00e-07

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|
gi 1804876928 1155 AMYDYVANNEDELNFSKGQLINVLNKDDPDWWQGEINGVTGLFPSNYVKM 1204
Cdd:cd11928      5 ALYSYEGKEPGDLKFNKGDIIILRRKVDENWYHGELNGCHGFLPASYIQC 54

SH3 domain; SH3 (Src homology 3) domains are often indicative of a protein involved in signal transduction related to cytoskeletal organization. First described in the Src cytoplasmic tyrosine kinase. The structure is a partly opened beta barrel.

Pssm-ID: 394975 [Multi-domain] Cd Length: 47 Bit Score: 49.89 E-value: 1.03e-07

                           10        20        30        40
                   ....*....|....*....|....*....|....*....|....*..
gi 1804876928 1084 AYVASGSEQLSLAPGQLILILKKNSSGWWQGELqargKKRQKGWFPA 1130
Cdd:pfam00018    5 DYTAQEPDELSFKKGDIIIVLEKSEDGWWKGRN----KGGKEGLIPS 47

RecF/RecN/SMC N terminal domain; This domain is found at the N terminus of SMC proteins. The SMC (structural maintenance of chromosomes) superfamily proteins have ATP-binding domains at the N- and C-termini, and two extended coiled-coil domains separated by a hinge in the middle. The eukaryotic SMC proteins form two kind of heterodimers: the SMC1/SMC3 and the SMC2/SMC4 types. These heterodimers constitute an essential part of higher order complexes, which are involved in chromatin and DNA dynamics. This family also includes the RecF and RecN proteins that are involved in DNA metabolism and recombination.

Pssm-ID: 426784 [Multi-domain] Cd Length: 1161 Bit Score: 57.29 E-value: 1.06e-07

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1804876928  384 QKIQEEEPQKKLPVTFEDKRKANYERGNVELEKRRQALMEQQQREAERK----------AQKEKEEWERKQRELQEQEWK 453
Cdd:pfam02463  281 KKLQEEELKLLAKEEEELKSELLKLERRKVDDEEKLKESEKEKKKAEKElkkekeeieeLEKELKELEIKREAEEEEEEE 360

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1804876928  454 KQLELEKRLEKQrelerqreeeRRKEIERREAAKQELERQRRLEWERIRRQELLNQRNREQEEIVRLNSKKKSLHLELEA 533
Cdd:pfam02463  361 LEKLQEKLEQLE----------EELLAKKKLESERLSSAAKLKEEELELKSEEEKEAQLLLELARQLEDLLKEEKKEELE 430

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1804876928  534 LNGKHQQisgRLQDVRLRKQTQKTEIEVLDKQCDLEIMEIKQLQQELQDYQNKLIYLVPEKQL---LNERIKNMQLGNTP 610
Cdd:pfam02463  431 ILEEEEE---SIELKQGKLTEEKEELEKQELKLLKDELELKKSEDLLKETQLVKLQEQLELLLsrqKLEERSQKESKARS 507

                          250       260       270       280       290       300       310       320
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1804876928  611 DLGIDLLHKKSLEKEELCQ---RLKEQLDALEKETASKLSEMDSFNNQL--------KCGNMDDSVLQCLLSLLSCLNNL 679
Cdd:pfam02463  508 GLKVLLALIKDGVGGRIISahgRLGDLGVAVENYKVAISTAVIVEVSATadeveerqKLVRALTELPLGARKLRLLIPKL 587

                          330       340       350       360       370       380       390       400
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1804876928  680 FLLLKELRESYNTQQLALEQLHKI-----------KRDKLKEIERKRSELIQKKKLEDEAIRKAKQGKENLWRESLRK-- 746
Cdd:pfam02463  588 KLPLKSIAVLEIDPILNLAQLDKAtleadeddkraKVVEGILKDTELTKLKESAKAKESGLRKGVSLEEGLAEKSEVKas 667

                          410       420       430
                   ....*....|....*....|....*....|.
gi 1804876928  747 EEEEKQKRLQEEKTQEKVQEEERKVEEKQCE 777
Cdd:pfam02463  668 LSELTKELLEIQELQEKAESELAKEEILRRQ 698

Src homology 3 domains of the p47phox subunit of NADPH oxidase and similar domains; This family is composed of the tandem SH3 domains of p47phox subunit of NADPH oxidase and Nox Organizing protein 1 (NoxO1), the four SH3 domains of Tks4 (Tyr kinase substrate with four SH3 domains), the five SH3 domains of Tks5, the SH3 domain of obscurin, Myosin-I, and similar domains. Most members of this group also contain Phox homology (PX) domains, except for obscurin and Myosin-I. p47phox and NoxO1 are regulators of the phagocytic NADPH oxidase complex (also called Nox2 or gp91phox) and nonphagocytic NADPH oxidase Nox1, respectively. They play roles in the activation of their respective NADPH oxidase, which catalyzes the transfer of electrons from NADPH to molecular oxygen to form superoxide. Tks proteins are Src substrates and scaffolding proteins that play important roles in the formation of podosomes and invadopodia, the dynamic actin-rich structures that are related to cell migration and cancer cell invasion. Obscurin is a giant muscle protein that plays important roles in the organization and assembly of the myofibril and the sarcoplasmic reticulum. Type I myosins (Myosin-I) are actin-dependent motors in endocytic actin structures and actin patches. They play roles in membrane traffic in endocytic and secretory pathways, cell motility, and mechanosensing. Myosin-I contains an N-terminal actin-activated ATPase, a phospholipid-binding TH1 (tail homology 1) domain, and a C-terminal extension which includes an F-actin-binding TH2 domain, an SH3 domain, and an acidic peptide that participates in activating the Arp2/3complex. The SH3 domain of myosin-I is required for myosin-I-induced actin polymerization. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212790 [Multi-domain] Cd Length: 53 Bit Score: 49.94 E-value: 1.13e-07

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....
gi 1804876928 1081 VTSAYVASGSEQLSLAPGQLILILKKNSSGWWQGElqargKKRQKGWFPASHVK 1134
Cdd:cd11856      4 AIADYEAQGDDEISLQEGEVVEVLEKNDSGWWYVR-----KGDKEGWVPASYLE 52

First Src Homology 3 domain of SH3 domain containing ring finger proteins; This model represents the first SH3 domain of SH3RF1 (or POSH), SH3RF2 (or POSHER), SH3RF3 (POSH2), and similar domains. Members of this family are scaffold proteins that function as E3 ubiquitin-protein ligases. They all contain an N-terminal RING finger domain and multiple SH3 domains; SH3RF1 and SH3RF3 have four SH3 domains while SH3RF2 has three. SH3RF1 plays a role in calcium homeostasis through the control of the ubiquitin domain protein Herp. It may also have a role in regulating death receptor mediated and JNK mediated apoptosis. SH3RF3 interacts with p21-activated kinase 2 (PAK2) and GTP-loaded Rac1. It may play a role in regulating JNK mediated apoptosis in certain conditions. SH3RF2 acts as an anti-apoptotic regulator of the JNK pathway by binding to and promoting the degradation of SH3RF1. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212720 [Multi-domain] Cd Length: 53 Bit Score: 50.05 E-value: 1.14e-07

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....*.
gi 1804876928  786 KALYRFEARSHDEMSFNSGDII----QVDEKtigepgWLYGSFQGNFGWFPCNYVE 837
Cdd:cd11786      3 KALYNYEGKEPGDLSFKKGDIIllrkRIDEN------WYHGECNGKQGFFPASYVQ 52

MAEBL; Provisional

Pssm-ID: 173412 [Multi-domain] Cd Length: 2084 Bit Score: 57.07 E-value: 1.21e-07

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1804876928  372 QIDSINGTLPSY--------QKIQEEEPQKKLPVTFEDKRKAnyERGNVELEKRRQALMEQQQrEAERKAQKEKEEWERK 443
Cdd:PTZ00121  1065 HVGQDEGLKPSYkdfdfdakEDNRADEATEEAFGKAEEAKKT--ETGKAEEARKAEEAKKKAE-DARKAEEARKAEDARK 1141

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1804876928  444 QRELQEQEWKKQLELEKRLEKqreLERQREEERRKEIERREAAKQELERQRRLEW---ERIRRQELLN--QRNREQEEIV 518
Cdd:PTZ00121  1142 AEEARKAEDAKRVEIARKAED---ARKAEEARKAEDAKKAEAARKAEEVRKAEELrkaEDARKAEAARkaEEERKAEEAR 1218

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1804876928  519 RLNSKKKSLHLELEALNGKHQQISGRLQDVRLRKQTQKTEiEVLDKQCDLEIMEIKQLQQELQDYQNKliylVPEKQLLN 598
Cdd:PTZ00121  1219 KAEDAKKAEAVKKAEEAKKDAEEAKKAEEERNNEEIRKFE-EARMAHFARRQAAIKAEEARKADELKK----AEEKKKAD 1293

                          250       260       270       280       290       300       310       320
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1804876928  599 ERIKNMQLGNTPDLG--------IDLLHKKSLEKEELCQRLKEQLDALEKETASKLSEMDSFNNQLKCGNMDDSVLQCLL 670
Cdd:PTZ00121  1294 EAKKAEEKKKADEAKkkaeeakkADEAKKKAEEAKKKADAAKKKAEEAKKAAEAAKAEAEAAADEAEAAEEKAEAAEKKK 1373

                          330       340       350       360       370       380       390       400
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1804876928  671 SLLSCLNNLFLL-LKELRESYNTQQLALEQLHKIKRDKLKEIERKRSELIQKKKLE----DEAIRKAKQGKEnlwRESLR 745
Cdd:PTZ00121  1374 EEAKKKADAAKKkAEEKKKADEAKKKAEEDKKKADELKKAAAAKKKADEAKKKAEEkkkaDEAKKKAEEAKK---ADEAK 1450

                          410       420       430
                   ....*....|....*....|....*....|...
gi 1804876928  746 KEEEEKQKRLQEEKTQE---KVQEEERKVEEKQ 775
Cdd:PTZ00121  1451 KKAEEAKKAEEAKKKAEeakKADEAKKKAEEAK 1483

First C-terminal Src homology 3 domain of SH3 and cysteine-rich domain-containing protein 3 (Stac3); Stac proteins are putative adaptor proteins that contain a cysteine-rich C1 domain and one or two SH3 domains at the C-terminus. There are three mammalian members (Stac1, Stac2, and Stac3) of this family. Stac1 and Stac3 contain two SH3 domains while Stac2 contains a single SH3 domain at the C-terminus. Stac1 and Stac2 have been found to be expressed differently in mature dorsal root ganglia (DRG) neurons. Stac1 is mainly expressed in peptidergic neurons while Stac2 is found in a subset of nonpeptidergic and all trkB+ neurons. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212919 [Multi-domain] Cd Length: 53 Bit Score: 49.91 E-value: 1.25e-07

                           10        20        30        40
                   ....*....|....*....|....*....|....*....|....*....
gi 1804876928 1154 IAMYDYVANNEDELNFSKGQLINVLNKDDPDWWQGEINGVTGLFPSNYV 1202
Cdd:cd11986      3 VALYRFKALEKDDLDFHPGERITVIDDSNEEWWRGKIGEKTGYFPMNFI 51

Src Homology 3 domain of Membrane Protein, Palmitoylated (or MAGUK p55 subfamily member) proteins; The MPP/p55 subfamily of MAGUK (membrane-associated guanylate kinase) proteins includes at least eight vertebrate members (MPP1-7 and CASK), four Drosophila proteins (Stardust, Varicose, CASK and Skiff), and other similar proteins; they all contain one each of the core of three domains characteristic of MAGUK proteins: PDZ, SH3, and guanylate kinase (GuK). In addition, most members except for MPP1 contain N-terminal L27 domains and some also contain a Hook (Protein 4.1 Binding) motif in between the SH3 and GuK domains. CASK has an additional calmodulin-dependent kinase (CaMK)-like domain at the N-terminus. Members of this subfamily are scaffolding proteins that play important roles in regulating and establishing cell polarity, cell adhesion, and synaptic targeting and transmission, among others. The GuK domain in MAGUK proteins is enzymatically inactive; instead, the domain mediates protein-protein interactions and associates intramolecularly with the SH3 domain. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212796 Cd Length: 61 Bit Score: 49.89 E-value: 1.27e-07

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....*.
gi 1804876928 1155 AMYDYVANNEDE-------LNFSKGQLINVLNKDDPDWWQ----GEINGVTGLFPS 1199
Cdd:cd11862      4 ALFDYDPEEDPLipckeagLSFKKGDILQIVNQDDPNWWQarkvGDPNGRAGLIPS 59

Arginine and glutamate-rich 1; ARGLU, arginine and glutamate-rich 1 protein family, is required for the oestrogen-dependent expression of ESR1 target genes. It functions in cooperation with MED1. The family of proteins is found in eukaryotes.

Pssm-ID: 405931 [Multi-domain] Cd Length: 151 Bit Score: 52.75 E-value: 1.29e-07

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1804876928  384 QKIQEEEPQKKLPVTFEDKRKAnyERGNVELEKRRQALMEQQqREAERKAQKEKEEWERKQRE----LQEQEWKKQLELE 459
Cdd:pfam15346   22 KRVEEELEKRKDEIEAEVERRV--EEARKIMEKQVLEELERE-REAELEEERRKEEEERKKREelerILEENNRKIEEAQ 98

                           90       100       110       120       130       140
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 1804876928  460 KRLEKQRELerqreeerrkeierreaakqELERQRRLEWERIRRQELLNQRNREQEEIVrLNSKK 524
Cdd:pfam15346   99 RKEAEERLA--------------------MLEEQRRMKEERQRREKEEEEREKREQQKI-LNKKN 142

Second Src homology 3 domain (or SH3B) of Intersectin-2; Intersectin-2 (ITSN2) is an adaptor protein that functions in exo- and endocytosis, actin cytoskeletal reorganization, and signal transduction. It plays a role in clathrin-coated pit (CCP) formation. It binds to many proteins through its multidomain structure and facilitate the assembly of multimeric complexes. ITSN2 also functions as a specific GEF for Cdc42 activation in epithelial morphogenesis, and is required in mitotic spindle orientation. It exists in alternatively spliced short and long isoforms. The short isoform contains two Eps15 homology domains (EH1 and EH2), a coiled-coil region and five SH3 domains (SH3A-E), while the long isoform, in addition, contains RhoGEF (also called Dbl-homologous or DH), Pleckstrin homology (PH) and C2 domains. The second SH3 domain (or SH3B) of ITSN2 is expected to bind protein partners, similar to ITSN1 which has been shown to bind WNK and CdGAP. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212923 [Multi-domain] Cd Length: 52 Bit Score: 49.65 E-value: 1.30e-07

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|
gi 1804876928 1155 AMYDYVANNEDELNFSKGQLINVLNKDDpDWWQGEINGVTGLFPSNYVKM 1204
Cdd:cd11990      4 ALCSWTAKKDNHLNFSKNDIITVLEQQE-NWWFGEVHGGRGWFPKSYVKL 52

Src homology 3 domain of Cortactin; Cortactin was originally identified as a substrate of Src kinase. It is an actin regulatory protein that binds to the Arp2/3 complex and stabilizes branched actin filaments. It is involved in cellular processes that affect cell motility, adhesion, migration, endocytosis, and invasion. It is expressed ubiquitously except in hematopoietic cells, where the homolog hematopoietic lineage cell-specific 1 (HS1) is expressed instead. Cortactin contains an N-terminal acidic domain, several copies of a repeat domain found in cortactin and HS1, a proline-rich region, and a C-terminal SH3 domain. The N-terminal region interacts with the Arp2/3 complex and F-actin, and is crucial in regulating branched actin assembly. Cortactin also serves as a scaffold and provides a bridge to the actin cytoskeleton for membrane trafficking and signaling proteins that bind to its SH3 domain. Binding partners for the SH3 domain of cortactin include dynamin2, N-WASp, MIM, FGD1, among others. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212892 [Multi-domain] Cd Length: 53 Bit Score: 49.72 E-value: 1.35e-07

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|..
gi 1804876928  786 KALYRFEARSHDEMSFNSGDIIqVDEKTIGEpGWLYGSFQGNFGWFPCNYVE 837
Cdd:cd11959      3 VALYDYQAADDDEISFDPDDII-TNIEMIDE-GWWRGVCRGKYGLFPANYVE 52

C-terminal Src Homology 3 domain of the p67phox subunit of NADPH oxidase and similar proteins; This subfamily is composed of p67phox, NADPH oxidase activator 1 (Noxa1), and similar proteins. p67phox, also called Neutrophil cytosol factor 2 (NCF-2), and Noxa1 are homologs and are the cytosolic subunits of the phagocytic (Nox2) and nonphagocytic (Nox1) NADPH oxidase complexes, respectively. NADPH oxidase catalyzes the transfer of electrons from NADPH to oxygen during phagocytosis forming superoxide and reactive oxygen species. p67phox and Noxa1 play regulatory roles. p67phox contains N-terminal TPR, first SH3 (or N-terminal or central SH3), PB1, and C-terminal SH3 domains. Noxa1 has a similar domain architecture except it is lacking the N-terminal SH3 domain. The TPR domain of both binds activated GTP-bound Rac, while the C-terminal SH3 domain of p67phox and Noxa1 binds the polyproline motif found at the C-terminus of p47phox and Noxo1, respectively. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212803 [Multi-domain] Cd Length: 53 Bit Score: 49.83 E-value: 1.35e-07

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|..
gi 1804876928 1152 QVIAMYDYVANNEDELNFSKGQLINVLNKDDPDWWQGEINGVTGLFPSNYVK 1203
Cdd:cd11870      1 QVVALHRYEAQGPEDLGFREGDTIDVLSEVNEAWLEGHSDGRVGIFPKCFVV 52

Src homology 3 domain of Protein kinase C and Casein kinase Substrate in Neurons 3 (PACSIN3); PACSIN 3 or Syndapin III (Synaptic dynamin-associated protein III) is expressed ubiquitously and regulates glucose uptake in adipocytes through its role in GLUT1 trafficking. It also modulates the subcellular localization and stimulus-specific function of the cation channel TRPV4. PACSINs act as regulators of cytoskeletal and membrane dynamics. Vetebrates harbor three isoforms with distinct expression patterns and specific functions. PACSINs contain an N-terminal F-BAR domain and a C-terminal SH3 domain. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212930 [Multi-domain] Cd Length: 56 Bit Score: 49.96 E-value: 1.38e-07

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....
gi 1804876928 1152 QVIAMYDYVANNEDELNFSKG-QLINVLNKDDPDWWQGEI-NGVTGLFPSNYVK 1203
Cdd:cd11997      3 RVRALYDYTGQEADELSFKAGeELLKIGEEDEQGWCKGRLlSGRIGLYPANYVE 56

First Src homology 3 domain (or SH3A) of Intersectin; Intersectins (ITSNs) are adaptor proteins that function in exo- and endocytosis, actin cytoskeletal reorganization, and signal transduction. They are essential for initiating clathrin-coated pit formation. They bind to many proteins through their multidomain structure and facilitate the assembly of multimeric complexes. Vertebrates contain two ITSN proteins, ITSN1 and ITSN2, which exist in alternatively spliced short and long isoforms. The short isoforms contain two Eps15 homology domains (EH1 and EH2), a coiled-coil region and five SH3 domains (SH3A-E), while the long isoforms, in addition, contain RhoGEF (also called Dbl-homologous or DH), Pleckstrin homology (PH) and C2 domains. ITSN1 and ITSN2 are both widely expressed, with variations depending on tissue type and stage of development. The first SH3 domain (or SH3A) of ITSN1 has been shown to bind many proteins including Sos1, dynamin1/2, CIN85, c-Cbl, PI3K-C2, SHIP2, N-WASP, and CdGAP, among others. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212770 [Multi-domain] Cd Length: 55 Bit Score: 49.66 E-value: 1.38e-07

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|...
gi 1804876928  923 KAQALCSWTAKKDNHLNFSKHDIITVLEQQEN---WWFGEVHGGRGWFPKSYV 972
Cdd:cd11836      1 KYRALYAFEARNPDEISFQPGDIIQVDESQVAepgWLAGELKGKTGWFPANYV 53

Second Src Homology 3 domain of Nck adaptor proteins; Nck adaptor proteins regulate actin cytoskeleton dynamics by linking proline-rich effector molecules to protein tyrosine kinases and phosphorylated signaling intermediates. They contain three SH3 domains and a C-terminal SH2 domain. They function downstream of the PDGFbeta receptor and are involved in Rho GTPase signaling and actin dynamics. Vertebrates contain two Nck adaptor proteins: Nck1 (also called Nckalpha) and Nck2 (also called Nckbeta or Growth factor receptor-bound protein 4, Grb4), which show partly overlapping functions but also bind distinct targets. Their SH3 domains are involved in recruiting downstream effector molecules, such as the N-WASP/Arp2/3 complex, which when activated induces actin polymerization that results in the production of pedestals, or protrusions of the plasma membrane. The second SH3 domain of Nck appears to prefer ligands containing the APxxPxR motif. SH3 domains are protein interaction domains that usually bind to proline-rich ligands with moderate affinity and selectivity, preferentially a PxxP motif. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212700 [Multi-domain] Cd Length: 53 Bit Score: 49.57 E-value: 1.41e-07

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|.
gi 1804876928  923 KAQALCSWTAKKDNHLNFSKHDIITVLEQQEN-WWFGEVHGGRGWFPKSYV 972
Cdd:cd11766      1 PAVVKFNYEAQREDELSLRKGDRVLVLEKSSDgWWRGECNGQVGWFPSNYV 51

Src Homology 3 domain of beta-Pak Interactive eXchange factor; Beta-PIX, also called Rho guanine nucleotide exchange factor 7 (ARHGEF7) or Cool (Cloned out of Library)-1, activates small GTPases by exchanging bound GDP for free GTP. It acts as a GEF for both Cdc42 and Rac 1, and plays important roles in regulating neuroendocrine exocytosis, focal adhesion maturation, cell migration, synaptic vesicle localization, and insulin secretion. PIX proteins contain an N-terminal SH3 domain followed by RhoGEF (also called Dbl-homologous or DH) and Pleckstrin Homology (PH) domains, and a C-terminal leucine-zipper domain for dimerization. The SH3 domain of PIX binds to an atypical PxxxPR motif in p21-activated kinases (PAKs) with high affinity. The binding of PAKs to PIX facilitate the localization of PAKs to focal complexes and also localizes PAKs to PIX targets Cdc43 and Rac, leading to the activation of PAKs. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212994 [Multi-domain] Cd Length: 54 Bit Score: 49.68 E-value: 1.42e-07

                           10        20        30        40
                   ....*....|....*....|....*....|....*....|....*....
gi 1804876928 1009 ALYSYSSVEPGDLTFIEGEEILVT-QKDGEWWTGSIGDRTGIFPSNYVK 1056
Cdd:cd12061      4 AKFNFQQTNEDELSFSKGDVIHVTrVEEGGWWEGTHNGRTGWFPSNYVR 52

Family of unknown function (DUF5401); This is a family of unknown function found in Chromadorea.

Pssm-ID: 375164 [Multi-domain] Cd Length: 722 Bit Score: 56.67 E-value: 1.44e-07

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1804876928  380 LPSYQKIQEEEPQKKLPVTFEDKRKAnYERgNVELEKRRQalmEQQQREAERKAQKE-------KEEWERKQRELQEQEW 452
Cdd:pfam17380  318 LEEAEKARQAEMDRQAAIYAEQERMA-MER-ERELERIRQ---EERKRELERIRQEEiameisrMRELERLQMERQQKNE 392

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1804876928  453 KKQLELE-----KRLEKQRELERQREEERRKE-IERREAAKQE----LERQRRLEWERIRRQELLNQ----RNREQEEiv 518
Cdd:pfam17380  393 RVRQELEaarkvKILEEERQRKIQQQKVEMEQiRAEQEEARQRevrrLEEERAREMERVRLEEQERQqqveRLRQQEE-- 470

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1804876928  519 rlNSKKKSLHLElealngKHQQISGRLQDvrLRKQTQKTEIEVLDKQCDLEIMEIKQLQQELQDYQNKLIYLVPEKQLLN 598
Cdd:pfam17380  471 --ERKRKKLELE------KEKRDRKRAEE--QRRKILEKELEERKQAMIEEERKRKLLEKEMEERQKAIYEEERRREAEE 540

                          250       260       270       280
                   ....*....|....*....|....*....|....*....|...
gi 1804876928  599 ERIKNMQLGNtpdlgidllHKKSLEKEELCQRLKEQLDALEKE 641
Cdd:pfam17380  541 ERRKQQEMEE---------RRRIQEQMRKATEERSRLEAMERE 574

Src homology 3 domain of Src Protein Tyrosine Kinase; Src (or c-Src) is a cytoplasmic (or non-receptor) PTK and is the vertebrate homolog of the oncogenic protein (v-Src) from Rous sarcoma virus. Together with other Src subfamily proteins, it is involved in signaling pathways that regulate cytokine and growth factor responses, cytoskeleton dynamics, cell proliferation, survival, and differentiation. Src also play a role in regulating cell adhesion, invasion, and motility in cancer cells, and tumor vasculature, contributing to cancer progression and metastasis. Elevated levels of Src kinase activity have been reported in a variety of human cancers. Several inhibitors of Src have been developed as anti-cancer drugs. Src is also implicated in acute inflammatory responses and osteoclast function. Src kinases contain an N-terminal SH4 domain with a myristoylation site, followed by SH3 and SH2 domains, a tyr kinase domain, and a regulatory C-terminal region containing a conserved tyr. They are activated by autophosphorylation at the tyr kinase domain, but are negatively regulated by phosphorylation at the C-terminal tyr by Csk (C-terminal Src Kinase). The SH3 domain of Src kinases contributes to substrate recruitment by binding adaptor proteins/substrates, and regulation of kinase activity through an intramolecular interaction. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212941 [Multi-domain] Cd Length: 56 Bit Score: 49.72 E-value: 1.44e-07

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|.
gi 1804876928 1154 IAMYDYVANNEDELNFSKGQLINVLNKDDPDWWQGE--INGVTGLFPSNYV 1202
Cdd:cd12008      3 VALYDYESRTETDLSFKKGERLQIVNNTEGDWWLAHslTTGQTGYIPSNYV 53

First Src Homology 3 domain of SH3 domain containing ring finger 2; SH3RF2 is also called POSHER (POSH-eliminating RING protein) or HEPP1 (heart protein phosphatase 1-binding protein). It acts as an anti-apoptotic regulator of the JNK pathway by binding to and promoting the degradation of SH3RF1 (or POSH), a scaffold protein that is required for pro-apoptotic JNK activation. It may also play a role in cardiac functions together with protein phosphatase 1. SH3RF2 contains an N-terminal RING finger domain and three SH3 domains. This model represents the first SH3 domain, located at the N-terminal half, of SH3RF2. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212862 Cd Length: 54 Bit Score: 49.55 E-value: 1.57e-07

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|...
gi 1804876928  923 KAQALCSWTAKKDNHLNFSKHDIITVLEQ-QENWWFGEVHGGRGWFPKSYVKI 974
Cdd:cd11929      2 RAKALCNYRGHNPGDLKFNKGDVILLRRQlDENWYLGEINGVSGIFPASSVEV 54

Src Homology 3 domain of Mixed Lineage Kinases 1, 2, and 3; MLKs 1, 2, and 3 are Serine/Threonine Kinases (STKs), catalyzing the transfer of the gamma-phosphoryl group from ATP to S/T residues on protein substrates. MLKs act as mitogen-activated protein kinase kinase kinases (MAP3Ks, MKKKs, MAPKKKs), which phosphorylate and activate MAPK kinases (MAPKKs or MKKs or MAP2Ks), which in turn phosphorylate and activate MAPKs during signaling cascades that are important in mediating cellular responses to extracellular signals. MLKs play roles in immunity and inflammation, as well as in cell death, proliferation, and cell cycle regulation. Little is known about the specific function of MLK1, also called MAP3K9. It is capable of activating the c-Jun N-terminal kinase pathway. Mice lacking both MLK1 and MLK2 are viable, fertile, and have normal life spans. MLK2, also called MAP3K10, is abundant in brain, skeletal muscle, and testis. It functions upstream of the MAPK, c-Jun N-terminal kinase. It binds hippocalcin, a calcium-sensor protein that protects neurons against calcium-induced cell death. Both MLK2 and hippocalcin may be associated with the pathogenesis of Parkinson's disease. MLK3, also called MAP3K11, is highly expressed in breast cancer cells and its signaling through c-Jun N-terminal kinase has been implicated in the migration, invasion, and malignancy of cancer cells. It also functions as a negative regulator of Inhibitor of Nuclear Factor-KappaB Kinase (IKK) and thus, impacts inflammation and immunity. MLKs contain an SH3 domain, a catalytic kinase domain, a leucine zipper, a proline-rich region, and a CRIB domain that mediates binding to GTP-bound Cdc42 and Rac. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212992 [Multi-domain] Cd Length: 58 Bit Score: 49.76 E-value: 1.58e-07

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|...
gi 1804876928  787 ALYRFEARSHDEMSFNSGDIIQV---DEKTIGEPGWLYGSFQGNFGWFPCNYV 836
Cdd:cd12059      4 AVFDYEASAEDELTLRRGDRVEVlskDSAVSGDEGWWTGKINDRVGIFPSNYV 56

Second Src homology 3 domain (or SH3B) of Intersectin; Intersectins (ITSNs) are adaptor proteins that function in exo- and endocytosis, actin cytoskeletal reorganization, and signal transduction. They are essential for initiating clathrin-coated pit formation. They bind to many proteins through their multidomain structure and facilitate the assembly of multimeric complexes. Vertebrates contain two ITSN proteins, ITSN1 and ITSN2, which exist in alternatively spliced short and long isoforms. The short isoforms contain two Eps15 homology domains (EH1 and EH2), a coiled-coil region and five SH3 domains (SH3A-E), while the long isoforms, in addition, contain RhoGEF (also called Dbl-homologous or DH), Pleckstrin homology (PH) and C2 domains. ITSN1 and ITSN2 are both widely expressed, with variations depending on tissue type and stage of development. The second SH3 domain (or SH3B) of ITSN1 has been shown to bind WNK and CdGAP. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212771 [Multi-domain] Cd Length: 53 Bit Score: 49.29 E-value: 1.65e-07

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|.
gi 1804876928  787 ALYRFEARSHDEMSFNSGDIIQVDEKtigEPGWLYGSFQ-GNFGWFPCNYV 836
Cdd:cd11837      4 ALYPWRAKKENHLSFAKGDIITVLEQ---QEMWWFGELEgGEEGWFPKSYV 51

Second Src Homology 3 domain of FCH and double SH3 domains proteins; This group is composed of FCH and double SH3 domains protein 1 (FCHSD1) and FCHSD2. These proteins have a common domain structure consisting of an N-terminal F-BAR (FES-CIP4 Homology and Bin/Amphiphysin/Rvs), two SH3, and C-terminal proline-rich domains. They have only been characterized in silico and their functions remain unknown. This group also includes the insect protein, nervous wreck, which acts as a regulator of synaptic growth signaling. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212696 [Multi-domain] Cd Length: 57 Bit Score: 49.70 E-value: 1.69e-07

                           10        20        30        40
                   ....*....|....*....|....*....|....*....|....*....
gi 1804876928 1009 ALYSYSSVEPGDLTFIEGEEILVTQKDGE-----WWTGSIGDRTGIFPS 1052
Cdd:cd11762      4 ALYDYEAQSDEELSFPEGAIIRILRKDDNgvddgWWEGEFNGRVGVFPS 52

Src homology 3 domain of eumetazoan Actin-binding protein 1; Abp1, also called drebrin-like protein, is an adaptor protein that functions in receptor-mediated endocytosis and vesicle trafficking. It contains an N-terminal actin-binding module, the actin-depolymerizing factor (ADF) homology domain, a helical domain, and a C-terminal SH3 domain. Mammalian Abp1, unlike yeast Abp1, does not contain an acidic domain that interacts with the Arp2/3 complex. It regulates actin dynamics indirectly by interacting with dynamin and WASP family proteins. Abp1 deficiency causes abnormal organ structure and function of the spleen, heart, and lung of mice. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212893 [Multi-domain] Cd Length: 54 Bit Score: 49.32 E-value: 1.79e-07

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....*..
gi 1804876928  786 KALYRFEARSHDEMSFNSGDII----QVDEktigepGWLYGSFQ-GNFGWFPCNYVE 837
Cdd:cd11960      3 RALYDYQAADDTEISFDPGDIItdieQIDE------GWWRGTGPdGTYGLFPANYVE 53

Third Src Homology 3 domain of SH3 domain containing ring finger 2; SH3RF2 is also called POSHER (POSH-eliminating RING protein) or HEPP1 (heart protein phosphatase 1-binding protein). It acts as an anti-apoptotic regulator of the JNK pathway by binding to and promoting the degradation of SH3RF1 (or POSH), a scaffold protein that is required for pro-apoptotic JNK activation. It may also play a role in cardiac functions together with protein phosphatase 1. SH3RF2 contains an N-terminal RING finger domain and three SH3 domains. This model represents the third SH3 domain, located in the middle, of SH3RF2. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212718 Cd Length: 55 Bit Score: 49.39 E-value: 1.88e-07

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|.
gi 1804876928 1154 IAMYDYVANNEDELNFSKGQLINVLNKDDPDWWQGE--INGVTGLFPSNYV 1202
Cdd:cd11784      3 VALHSYSAHRPEELELQKGEGVRVLGKFQEGWLRGLslVTGRVGIFPSNYV 53

Src homology 3 domain of Growth Arrest Specific protein 7; GAS7 is mainly expressed in the brain and is required for neurite outgrowth. It may also play a role in the protection and migration of embryonic stem cells. Treatment-related acute myeloid leukemia (AML) has been reported resulting from mixed-lineage leukemia (MLL)-GAS7 translocations as a complication of primary cancer treatment. GAS7 contains an N-terminal SH3 domain, followed by a WW domain, and a central F-BAR domain. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212763 [Multi-domain] Cd Length: 52 Bit Score: 49.05 E-value: 1.93e-07

                           10        20        30        40
                   ....*....|....*....|....*....|....*....|....*
gi 1804876928 1089 GSEQLSLAPGQLILILKKNSSGWWQGElqargKKRQKGWFPASHV 1133
Cdd:cd11829     13 HQQGLSFEAGELIRVLQAPDGGWWEGE-----KDGLRGWFPASYV 52

Third (or C-terminal) Src Homology 3 domain of Sorbin and SH3 domain containing (Sorbs) proteins and similar domains; This family, also called the vinexin family, is composed predominantly of adaptor proteins containing one sorbin homology (SoHo) and three SH3 domains. Members include the third SH3 domains of Sorbs1 (or ponsin), Sorbs2 (or ArgBP2), Vinexin (or Sorbs3), and similar domains. They are involved in the regulation of cytoskeletal organization, cell adhesion, and growth factor signaling. Members of this family bind multiple partners including signaling molecules like c-Abl, c-Arg, Sos, and c-Cbl, as well as cytoskeletal molecules such as vinculin and afadin. They may have overlapping functions. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212714 [Multi-domain] Cd Length: 55 Bit Score: 49.22 E-value: 1.95e-07

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|.
gi 1804876928 1155 AMYDYVANNEDELNFSKGQLINVLNKDDPDWWQG--EINGVTGLFPSNYVK 1203
Cdd:cd11780      4 ALYSYTPQNEDELELREGDIVYVMEKCDDGWFVGtsERTGLFGTFPGNYVA 54

Second Src Homology 3 domain of Nck adaptor proteins; Nck adaptor proteins regulate actin cytoskeleton dynamics by linking proline-rich effector molecules to protein tyrosine kinases and phosphorylated signaling intermediates. They contain three SH3 domains and a C-terminal SH2 domain. They function downstream of the PDGFbeta receptor and are involved in Rho GTPase signaling and actin dynamics. Vertebrates contain two Nck adaptor proteins: Nck1 (also called Nckalpha) and Nck2 (also called Nckbeta or Growth factor receptor-bound protein 4, Grb4), which show partly overlapping functions but also bind distinct targets. Their SH3 domains are involved in recruiting downstream effector molecules, such as the N-WASP/Arp2/3 complex, which when activated induces actin polymerization that results in the production of pedestals, or protrusions of the plasma membrane. The second SH3 domain of Nck appears to prefer ligands containing the APxxPxR motif. SH3 domains are protein interaction domains that usually bind to proline-rich ligands with moderate affinity and selectivity, preferentially a PxxP motif. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212700 [Multi-domain] Cd Length: 53 Bit Score: 49.19 E-value: 1.97e-07

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....*.
gi 1804876928 1078 IAQVTSAYVASGSEQLSLAPGQLILILKKNSSGWWQGELQArgkkrQKGWFPASHV 1133
Cdd:cd11766      1 PAVVKFNYEAQREDELSLRKGDRVLVLEKSSDGWWRGECNG-----QVGWFPSNYV 51

Third (or C-terminal) Src Homology 3 domain of Sorbin and SH3 domain containing (Sorbs) proteins and similar domains; This family, also called the vinexin family, is composed predominantly of adaptor proteins containing one sorbin homology (SoHo) and three SH3 domains. Members include the third SH3 domains of Sorbs1 (or ponsin), Sorbs2 (or ArgBP2), Vinexin (or Sorbs3), and similar domains. They are involved in the regulation of cytoskeletal organization, cell adhesion, and growth factor signaling. Members of this family bind multiple partners including signaling molecules like c-Abl, c-Arg, Sos, and c-Cbl, as well as cytoskeletal molecules such as vinculin and afadin. They may have overlapping functions. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212714 [Multi-domain] Cd Length: 55 Bit Score: 49.22 E-value: 1.99e-07

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....*.
gi 1804876928  785 YKALYRFEARSHDEMSFNSGDIIQVDEKTigEPGWLYGSFQ--GNFGWFPCNYVEK 838
Cdd:cd11780      2 YRALYSYTPQNEDELELREGDIVYVMEKC--DDGWFVGTSErtGLFGTFPGNYVAR 55

Protein of unknown function (DUF3584); This protein is found in bacteria and eukaryotes. Proteins in this family are typically between 943 to 1234 amino acids in length. This family contains a P-loop motif suggesting it is a nucleotide binding protein. It may be involved in replication.

Pssm-ID: 432349 [Multi-domain] Cd Length: 1191 Bit Score: 56.39 E-value: 2.03e-07

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1804876928  380 LPSYQKIQEEEPQKKLPVTFEDKRKANYE--RGNVE--LEKRRQALMEQQQREAERKAQKEKEEWERKQREL-------- 447
Cdd:pfam12128  339 IETAAADQEQLPSWQSELENLEERLKALTgkHQDVTakYNRRRSKIKEQNNRDIAGIKDKLAKIREARDRQLavaeddlq 418

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1804876928  448 -QEQEWKKQLELEKRlekqrelerqreeerrkeierrEAAKQELERQRRLEWERIR-------RQELLNQR------NRE 513
Cdd:pfam12128  419 aLESELREQLEAGKL----------------------EFNEEEYRLKSRLGELKLRlnqatatPELLLQLEnfderiERA 476

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1804876928  514 QEEIVRLNSKKKSLHLELEALNGKHQQISGRLQDVRLRKQTQKTEIEVLDKQCDLEIME-IKQLQQELQDYQNKLIYLVP 592
Cdd:pfam12128  477 REEQEAANAEVERLQSELRQARKRRDQASEALRQASRRLEERQSALDELELQLFPQAGTlLHFLRKEAPDWEQSIGKVIS 556

                          250       260       270       280       290       300       310       320
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1804876928  593 EKQL----LNERIKNMQLGNTPDLGIDLLHKKSLEKEE---LCQRLKEQLDALEKETASKLSEMDSFNNQLKCGNMDDSV 665
Cdd:pfam12128  557 PELLhrtdLDPEVWDGSVGGELNLYGVKLDLKRIDVPEwaaSEEELRERLDKAEEALQSAREKQAAAEEQLVQANGELEK 636

                          330       340       350       360       370       380       390       400
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1804876928  666 LQCLlsllsclnnlfllLKELRESYNTQQLALEQLHKIKRDKLKEIERKRSEliQKKKLEDEAIRKAKQGKENLWRESLR 745
Cdd:pfam12128  637 ASRE-------------ETFARTALKNARLDLRRLFDEKQSEKDKKNKALAE--RKDSANERLNSLEAQLKQLDKKHQAW 701

                          410       420       430       440
                   ....*....|....*....|....*....|....*....|....*.
gi 1804876928  746 KEEEEKQKRLQEEKTQEKVQ--EEERKVEEKQC--EPASALVNYKA 787
Cdd:pfam12128  702 LEEQKEQKREARTEKQAYWQvvEGALDAQLALLkaAIAARRSGAKA 747

Myosin tail; The myosin molecule is a multi-subunit complex made up of two heavy chains and four light chains it is a fundamental contractile protein found in all eukaryote cell types. This family consists of the coiled-coil myosin heavy chain tail region. The coiled-coil is composed of the tail from two molecules of myosin. These can then assemble into the macromolecular thick filament. The coiled-coil region provides the structural backbone the thick filament.

Pssm-ID: 460256 [Multi-domain] Cd Length: 1081 Bit Score: 56.34 E-value: 2.07e-07

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1804876928  400 EDKRKANyERGNVELEKRRQAL-----------MEQQQREAERKAQKEKEEWE-------------------RKQRELQE 449
Cdd:pfam01576  193 EERLKKE-EKGRQELEKAKRKLegestdlqeqiAELQAQIAELRAQLAKKEEElqaalarleeetaqknnalKKIRELEA 271

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1804876928  450 Q--EWKKQLELEK----RLEKQRELERQREEerrkeierreAAKQELERQRRlewERIRRQELLNQRNREQEEIVR-LNS 522
Cdd:pfam01576  272 QisELQEDLESERaarnKAEKQRRDLGEELE----------ALKTELEDTLD---TTAAQQELRSKREQEVTELKKaLEE 338

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1804876928  523 KKKSLHLELEALNGKHQQISGRLQD---------VRLRKQTQKTEIEVLDKQCDLEIMEI---------KQLQQELQDYQ 584
Cdd:pfam01576  339 ETRSHEAQLQEMRQKHTQALEELTEqleqakrnkANLEKAKQALESENAELQAELRTLQQakqdsehkrKKLEGQLQELQ 418

                          250       260       270       280       290       300       310       320
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1804876928  585 NKLIYLVPEKQLLNERiknmqlgntpdlgidlLHKKSLEKEELCQRLKEqldaLEKETASKLSEMDSFNNQLKcgnmD-D 663
Cdd:pfam01576  419 ARLSESERQRAELAEK----------------LSKLQSELESVSSLLNE----AEGKNIKLSKDVSSLESQLQ----DtQ 474

                          330       340       350       360       370       380       390       400
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1804876928  664 SVLQCLLSLLSCLNNLfllLKELRESYNTQQLALEQLHKIKRDKLKEIERKRSELIQ-KKKLEDEA--IRKAKQGKENLW 740
Cdd:pfam01576  475 ELLQEETRQKLNLSTR---LRQLEDERNSLQEQLEEEEEAKRNVERQLSTLQAQLSDmKKKLEEDAgtLEALEEGKKRLQ 551

                          410       420       430
                   ....*....|....*....|....*....|
gi 1804876928  741 R--ESLRKEEEEKQKRLQE-EKTQEKVQEE 767
Cdd:pfam01576  552 RelEALTQQLEEKAAAYDKlEKTKNRLQQE 581

Src homology 3 domain of Src kinase-like Protein Tyrosine Kinases; Src subfamily members include Src, Lck, Hck, Blk, Lyn, Fgr, Fyn, Yrk, Yes, and Brk. Src (or c-Src) proteins are cytoplasmic (or non-receptor) PTKs which are anchored to the plasma membrane. They contain an N-terminal SH4 domain with a myristoylation site, followed by SH3 and SH2 domains, a tyr kinase domain, and a regulatory C-terminal region containing a conserved tyr. They are activated by autophosphorylation at the tyr kinase domain, but are negatively regulated by phosphorylation at the C-terminal tyr by Csk (C-terminal Src Kinase). However, Brk lacks the N-terminal myristoylation sites. Src proteins are involved in signaling pathways that regulate cytokine and growth factor responses, cytoskeleton dynamics, cell proliferation, survival, and differentiation. They were identified as the first proto-oncogene products, and they regulate cell adhesion, invasion, and motility in cancer cells, and tumor vasculature, contributing to cancer progression and metastasis. Src kinases are overexpressed in a variety of human cancers, making them attractive targets for therapy. They are also implicated in acute inflammatory responses and osteoclast function. Src, Fyn, Yes, and Yrk are widely expressed, while Blk, Lck, Hck, Fgr, Lyn, and Brk show a limited expression pattern. This subfamily also includes Drosophila Src42A, Src oncogene at 42A (also known as Dsrc41) which accumulates at sites of cell-cell or cell-matrix adhesion, and participates in Drosphila development and wound healing. It has been shown to promote tube elongation in the tracheal system, is essential for proper cell-cell matching during dorsal closure, and regulates cell-cell contacts in developing Drosophila eyes. The SH3 domain of Src kinases contributes to substrate recruitment by binding adaptor proteins/substrates, and regulation of kinase activity through an intramolecular interaction. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212779 [Multi-domain] Cd Length: 52 Bit Score: 49.12 E-value: 2.18e-07

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....*
gi 1804876928 1007 YIALYSYSSVEPGDLTFIEGEEILVTQK-DGEWW------TGsigdRTGIFPSNY 1054
Cdd:cd11845      2 YVALYDYEARTDDDLSFKKGDRLQILDDsDGDWWlarhlsTG----KEGYIPSNY 52

Second Src Homology 3 domain of FCH and double SH3 domains proteins; This group is composed of FCH and double SH3 domains protein 1 (FCHSD1) and FCHSD2. These proteins have a common domain structure consisting of an N-terminal F-BAR (FES-CIP4 Homology and Bin/Amphiphysin/Rvs), two SH3, and C-terminal proline-rich domains. They have only been characterized in silico and their functions remain unknown. This group also includes the insect protein, nervous wreck, which acts as a regulator of synaptic growth signaling. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212696 [Multi-domain] Cd Length: 57 Bit Score: 49.32 E-value: 2.18e-07

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....
gi 1804876928  786 KALYRFEARSHDEMSFNSGDIIQVDEKTIG--EPGWLYGSFQGNFGWFPCNYVE 837
Cdd:cd11762      3 RALYDYEAQSDEELSFPEGAIIRILRKDDNgvDDGWWEGEFNGRVGVFPSLVVE 56

Src homology 3 domain of Phospholipase C (PLC) gamma; PLC catalyzes the hydrolysis of phosphatidylinositol (4,5)-bisphosphate [PtdIns(4,5)P2] to produce Ins(1,4,5)P3 and diacylglycerol (DAG) in response to various receptors. Ins(1,4,5)P3 initiates the calcium signaling cascade while DAG functions as an activator of PKC. PLCgamma catalyzes this reaction in tyrosine kinase-dependent signaling pathways. It is activated and recruited to its substrate at the membrane. Vertebrates contain two forms of PLCgamma, PLCgamma1, which is widely expressed, and PLCgamma2, which is primarily found in haematopoietic cells. PLCgamma contains a Pleckstrin homology (PH) domain followed by an elongation factor (EF) domain, two catalytic regions of PLC domains that flank two tandem SH2 domains, followed by a SH3 domain and C2 domain. The SH3 domain of PLCgamma1 directly interacts with dynamin-1 and can serve as a guanine nucleotide exchange factor (GEF). It also interacts with Cbl, inhibiting its phosphorylation and activity. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212759 [Multi-domain] Cd Length: 54 Bit Score: 49.25 E-value: 2.24e-07

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|..
gi 1804876928  924 AQALCSWTAKKDNHLNFSKHDIIT-VLEQQENWWFGEVHGGR-GWFPKSYVK 973
Cdd:cd11825      2 VKALYDYRAQRPDELSFCKHAIITnVEKEDGGWWRGDYGGKKqKWFPANYVE 53

Src Homology 3 domain of alpha-Pak Interactive eXchange factor; Alpha-PIX, also called Rho guanine nucleotide exchange factor 6 (ARHGEF6) or Cool (Cloned out of Library)-2, activates small GTPases by exchanging bound GDP for free GTP. It acts as a GEF for both Cdc42 and Rac 1, and is localized in dendritic spines where it regulates spine morphogenesis. It controls dendritic length and spine density in the hippocampus. Mutations in the ARHGEF6 gene cause X-linked intellectual disability in humans. PIX proteins contain an N-terminal SH3 domain followed by RhoGEF (also called Dbl-homologous or DH) and Pleckstrin Homology (PH) domains, and a C-terminal leucine-zipper domain for dimerization. The SH3 domain of PIX binds to an atypical PxxxPR motif in p21-activated kinases (PAKs) with high affinity. The binding of PAKs to PIX facilitate the localization of PAKs to focal complexes and also localizes PAKs to PIX targets Cdc43 and Rac, leading to the activation of PAKs. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212993 Cd Length: 58 Bit Score: 49.23 E-value: 2.35e-07

                           10        20        30        40
                   ....*....|....*....|....*....|....*....|....*....
gi 1804876928 1009 ALYSYSSVEPGDLTFIEGEEILVTQ-KDGEWWTGSIGDRTGIFPSNYVK 1056
Cdd:cd12060      6 ARFNFKQTNEDELSVCKGDIIYVTRvEEGGWWEGTLNGKTGWFPSNYVR 54

Chromosome segregation ATPase Smc [Cell cycle control, cell division, chromosome partitioning];

Pssm-ID: 440809 [Multi-domain] Cd Length: 983 Bit Score: 56.10 E-value: 2.42e-07

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1804876928  383 YQKIQEEEPQKKLPVTF-----EDKRKANYERGNVELEKRRQALmEQQQREAERKAQKEKEEWERKQRELQEQEWKKQLE 457
Cdd:COG1196    215 YRELKEELKELEAELLLlklreLEAELEELEAELEELEAELEEL-EAELAELEAELEELRLELEELELELEEAQAEEYEL 293

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1804876928  458 LEKRLEKQRELERQReeerrkeierrEAAKQELERQRRLEWErirRQELLNQRNREQEEIVRLNSKKKSLHLELEALNGK 537
Cdd:COG1196    294 LAELARLEQDIARLE-----------ERRRELEERLEELEEE---LAELEEELEELEEELEELEEELEEAEEELEEAEAE 359

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1804876928  538 HQQISGRLQDVRLRKQTQKTEIEVLDKQCDLEIMEIKQLQQELQDYQNKLIYLVPEKQLLNERIKNMQLGNtpdlgIDLL 617
Cdd:COG1196    360 LAEAEEALLEAEAELAEAEEELEELAEELLEALRAAAELAAQLEELEEAEEALLERLERLEEELEELEEAL-----AELE 434

                          250       260       270       280       290       300       310       320
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1804876928  618 HKKSLEKEELCQRLKEQLDALEKETASKLSEMDSFNNQLKcgnmDDSVLQCLLSLLSCLNNLFLLLKELRESYntQQLAL 697
Cdd:COG1196    435 EEEEEEEEALEEAAEEEAELEEEEEALLELLAELLEEAAL----LEAALAELLEELAEAAARLLLLLEAEADY--EGFLE 508

                          330       340       350       360       370       380       390       400
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1804876928  698 EQLHKIKRDKLKEIERKRSELIQKKKLEDEAIRKA-----KQGKENLWRESLRKEEEEKQKRLQEEKTQEKVQEEERKVE 772
Cdd:COG1196    509 GVKAALLLAGLRGLAGAVAVLIGVEAAYEAALEAAlaaalQNIVVEDDEVAAAAIEYLKAAKAGRATFLPLDKIRARAAL 588

                          410       420       430
                   ....*....|....*....|....*....|....*...
gi 1804876928  773 EKQCEPASALVNYkALYRFEARSHDEMSFNSGDIIQVD 810
Cdd:COG1196    589 AAALARGAIGAAV-DLVASDLREADARYYVLGDTLLGR 625

First Src Homology 3 domain of SH3 domain containing ring finger protein 1, an E3 ubiquitin-protein ligase; SH3RF1 is also called POSH (Plenty of SH3s) or SH3MD2 (SH3 multiple domains protein 2). It is a scaffold protein that acts as an E3 ubiquitin-protein ligase. It plays a role in calcium homeostasis through the control of the ubiquitin domain protein Herp. It may also have a role in regulating death receptor mediated and JNK mediated apoptosis. SH3RF1 also enhances the ubiquitination of ROMK1 potassium channel resulting in its increased endocytosis. It contains an N-terminal RING finger domain and four SH3 domains. This model represents the first SH3 domain, located at the N-terminal half, of SH3RF1. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212860 Cd Length: 54 Bit Score: 49.18 E-value: 2.42e-07

                           10        20        30        40
                   ....*....|....*....|....*....|....*....|....*....
gi 1804876928 1009 ALYSYSSVEPGDLTFIEGEEILV-TQKDGEWWTGSIGDRTGIFPSNYVK 1056
Cdd:cd11927      5 ALYNYEGKEPGDLKFSKGDIIILrRQVDENWYHGEVNGIHGFFPTNFVQ 53

SH3 domain; SH3 (Src homology 3) domains are often indicative of a protein involved in signal transduction related to cytoskeletal organization. First described in the Src cytoplasmic tyrosine kinase. The structure is a partly opened beta barrel.

Pssm-ID: 394975 [Multi-domain] Cd Length: 47 Bit Score: 48.74 E-value: 2.42e-07

                           10        20        30        40
                   ....*....|....*....|....*....|....*....|....*.
gi 1804876928  925 QALCSWTAKKDNHLNFSKHDIITVLEQQE-NWWFGEVHGGR-GWFP 968
Cdd:pfam00018    1 VALYDYTAQEPDELSFKKGDIIIVLEKSEdGWWKGRNKGGKeGLIP 46

Fifth Src homology 3 domain of ADAM-binding protein Eve-1; Eve-1, also called SH3 domain-containing protein 19 (SH3D19) or EEN-binding protein (EBP), exists in multiple alternatively spliced isoforms. The longest isoform contains five SH3 domain in the C-terminal region and seven proline-rich motifs in the N-terminal region. It is abundantly expressed in skeletal muscle and heart, and may be involved in regulating the activity of ADAMs (A disintegrin and metalloproteases). Eve-1 interacts with EEN, an endophilin involved in endocytosis and may be the target of the MLL-EEN fusion protein that is implicated in leukemogenesis. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212752 [Multi-domain] Cd Length: 50 Bit Score: 49.02 E-value: 2.47e-07

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|
gi 1804876928  923 KAQALCSWTAKKDNHLNFSKHDIITVLEQ-QENWWFGEVHGGRGWFPKSY 971
Cdd:cd11818      1 KARALYDFTGENEDELSFKAGDIITELESiDEEWMSGELRGKSGIFPKNF 50

Variant SH3 domain; SH3 (Src homology 3) domains are often indicative of a protein involved in signal transduction related to cytoskeletal organization. First described in the Src cytoplasmic tyrosine kinase. The structure is a partly opened beta barrel.

Pssm-ID: 429575 [Multi-domain] Cd Length: 54 Bit Score: 48.75 E-value: 2.53e-07

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....*...
gi 1804876928 1079 AQVTSAYVASGSEQLSLAPGQLILILKKNSSGWWQGELqargkKRQKGWFPASHVKLL 1136
Cdd:pfam07653    2 GRVIFDYVGTDKNGLTLKKGDVVKVLGKDNDGWWEGET-----GGRVGLVPSTAVEEI 54

Second Src Homology 3 domain of Sorbin and SH3 domain containing (Sorbs) proteins and similar domains; This family, also called the vinexin family, is composed predominantly of adaptor proteins containing one sorbin homology (SoHo) and three SH3 domains. Members include the second SH3 domains of Sorbs1 (or ponsin), Sorbs2 (or ArgBP2), Vinexin (or Sorbs3), and similar domains. They are involved in the regulation of cytoskeletal organization, cell adhesion, and growth factor signaling. Members of this family bind multiple partners including signaling molecules like c-Abl, c-Arg, Sos, and c-Cbl, as well as cytoskeletal molecules such as vinculin and afadin. They may have overlapping functions. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212716 [Multi-domain] Cd Length: 53 Bit Score: 48.89 E-value: 2.65e-07

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|..
gi 1804876928 1006 EYIALYSYSSVEPGDLTFIEGEEILVTQK-DGEWWTGSIGDRTGIFPSNYVK 1056
Cdd:cd11782      1 EARAKYNFNADTGVELSFRKGDVITLTRRvDENWYEGRIGGRQGIFPVSYVQ 52

Septal ring factor EnvC, activator of murein hydrolases AmiA and AmiB [Cell cycle control, cell division, chromosome partitioning];

Pssm-ID: 443969 [Multi-domain] Cd Length: 377 Bit Score: 54.77 E-value: 2.66e-07

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1804876928  502 RRQELLNQRNREQEEIVRLNSKKKSLHLELEALNGKHQQISGRLQDVRLRKQTQKTEIEVLDKQcdleimeIKQLQQELQ 581
Cdd:COG4942     28 ELEQLQQEIAELEKELAALKKEEKALLKQLAALERRIAALARRIRALEQELAALEAELAELEKE-------IAELRAELE 100

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1804876928  582 DyqnkliylvpEKQLLNERIKNMQ-LGNTPDLGIdLLHKKSLEK--------EELCQRLKEQLDALEKETASKLSEMDSF 652
Cdd:COG4942    101 A----------QKEELAELLRALYrLGRQPPLAL-LLSPEDFLDavrrlqylKYLAPARREQAEELRADLAELAALRAEL 169

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1804876928  653 NNQLKcgnmddsvlqcllsllsclnnlflLLKELRESYNTQQLALEQLHKIKRDKLKEIErkrseliQKKKLEDEAIRKA 732
Cdd:COG4942    170 EAERA------------------------ELEALLAELEEERAALEALKAERQKLLARLE-------KELAELAAELAEL 218

                          250       260
                   ....*....|....*....|....
gi 1804876928  733 KQGKENLWR--ESLRKEEEEKQKR 754
Cdd:COG4942    219 QQEAEELEAliARLEAEAAAAAER 242

Src homology 3 domain of Signal Transducing Adaptor Molecules; STAMs were discovered as proteins that are highly phosphorylated following cytokine and growth factor stimulation. They function in cytokine signaling and surface receptor degradation, as well as regulate Golgi morphology. They associate with many proteins including Jak2 and Jak3 tyrosine kinases, Hrs, AMSH, and UBPY. STAM adaptor proteins contain VHS (Vps27, Hrs, STAM homology), ubiquitin interacting (UIM), and SH3 domains. There are two vertebrate STAMs, STAM1 and STAM2, which may be functionally redundant; vertebrate STAMs contain ITAM motifs. They are part of the endosomal sorting complex required for transport (ESCRT-0). STAM2 deficiency in mice did not cause any obvious abnormality, while STAM1 deficiency resulted in growth retardation. Loss of both STAM1 and STAM2 in mice proved lethal, indicating that STAMs are important for embryonic development. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212754 [Multi-domain] Cd Length: 54 Bit Score: 49.00 E-value: 2.74e-07

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|...
gi 1804876928  786 KALYRFEARSHDEMSFNSGDIIQVDEKTigEPGWLYGSFQGNFGWFPCNYVEK 838
Cdd:cd11820      4 RALYDFEAAEDNELTFKAGEIITVLDDS--DPNWWKGSNHRGEGLFPANFVTA 54

Src homology 3 domain of ARHGEF9-like Rho guanine nucleotide exchange factors; Members of this family contain a SH3 domain followed by RhoGEF (also called Dbl-homologous or DH) and Pleckstrin Homology (PH) domains. They include the Rho guanine nucleotide exchange factors ARHGEF9, ASEF (also called ARHGEF4), ASEF2, and similar proteins. GEFs activate small GTPases by exchanging bound GDP for free GTP. ARHGEF9 specifically activates Cdc42, while both ASEF and ASEF2 can activate Rac1 and Cdc42. ARHGEF9 is highly expressed in the brain and it interacts with gephyrin, a postsynaptic protein associated with GABA and glycine receptors. ASEF plays a role in angiogenesis and cell migration. ASEF2 is important in cell migration and adhesion dynamics. ASEF exists in an autoinhibited form and is activated upon binding of the tumor suppressor APC (adenomatous polyposis coli), leading to the activation of Rac1 or Cdc42. In its autoinhibited form, the SH3 domain of ASEF forms an extensive interface with the DH and PH domains, blocking the Rac binding site. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212762 [Multi-domain] Cd Length: 53 Bit Score: 48.92 E-value: 2.80e-07

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|
gi 1804876928 1008 IALYSYSSVEPGDLTFIEGEEILVTQ-KDGEWWTGSIGDRTGIFPSNYVK 1056
Cdd:cd11828      3 EALWDHVTMDPEELGFKAGDVIEVLDmSDKDWWWGSIRDEEGWFPASFVR 52

Variant SH3 domain;

Pssm-ID: 434066 [Multi-domain] Cd Length: 49 Bit Score: 48.77 E-value: 2.87e-07

                           10        20        30        40
                   ....*....|....*....|....*....|....*....|....*....
gi 1804876928 1009 ALYSYSSVEPGDLTFIEGEEILVTQKDGE-WWTGSIGDRTGIFPSNYVK 1056
Cdd:pfam14604    1 ALYPYEPKDDDELSLQRGDVITVIEESEDgWWEGINTGRTGLVPANYVE 49

Src Homology 3 (SH3) domain of Inhibitor of ASPP protein (iASPP); iASPP, also called RelA-associated inhibitor (RAI), is an oncoprotein that inhibits the apoptotic transactivation potential of p53. It is upregulated in human breast cancers expressing wild-type p53, in acute leukemias regardless of the p53 mutation status, as well as in ovarian cancer where it is associated with poor patient outcome and chemoresistance. iASPP is also a binding partner and negative regulator of p65RelA, which promotes cell proliferation and inhibits apoptosis; p65RelA has the opposite effect on cell growth compared to the p53 family. It contains a proline-rich region, four ankyrin (ANK) repeats, and an SH3 domain at its C-terminal half. The SH3 domain and the ANK repeats of iASPP contribute to the p53 binding site; they bind to the DNA binding domain of p53. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212885 [Multi-domain] Cd Length: 56 Bit Score: 48.77 E-value: 3.12e-07

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|.
gi 1804876928 1153 VIAMYDYVANNEDELNFSKGQLINVLNKD--DPDWWQGEINGVTGLFPSNY 1201
Cdd:cd11952      3 VYALWDYSAEFPDELSFKEGDMVTVLRKDgeGTDWWWASLCGREGYVPRNY 53

Variant SH3 domain;

Pssm-ID: 434066 [Multi-domain] Cd Length: 49 Bit Score: 48.38 E-value: 3.16e-07

                           10        20        30        40
                   ....*....|....*....|....*....|....*....|....*....
gi 1804876928  926 ALCSWTAKKDNHLNFSKHDIITVLEQQEN-WWFGEVHGGRGWFPKSYVK 973
Cdd:pfam14604    1 ALYPYEPKDDDELSLQRGDVITVIEESEDgWWEGINTGRTGLVPANYVE 49

Second Src homology 3 domain (or SH3B) of Intersectin-1; Intersectin-1 (ITSN1) is an adaptor protein that functions in exo- and endocytosis, actin cytoskeletal reorganization, and signal transduction. It plays a role in clathrin-coated pit (CCP) formation. It binds to many proteins through its multidomain structure and facilitate the assembly of multimeric complexes. ITSN1 localizes in membranous organelles, CCPs, the Golgi complex, and may be involved in the cell membrane trafficking system. It exists in alternatively spliced short and long isoforms. The short isoform contains two Eps15 homology domains (EH1 and EH2), a coiled-coil region and five SH3 domains (SH3A-E), while the long isoform, in addition, contains RhoGEF (also called Dbl-homologous or DH), Pleckstrin homology (PH) and C2 domains. The second SH3 domain (or SH3B) of ITSN1 has been shown to bind WNK and CdGAP. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212922 [Multi-domain] Cd Length: 52 Bit Score: 48.56 E-value: 3.19e-07

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|...
gi 1804876928 1152 QVIAMYDYVANNEDELNFSKGQLINVLNKDDPdWWQGEINGVTGLFPSNYVKM 1204
Cdd:cd11989      1 QAQALYPWRAKKDNHLNFNKNDVITVLEQQDM-WWFGEVQGQKGWFPKSYVKL 52

Second Src Homology 3 domain of Nck2 adaptor protein; Nck2 (also called Nckbeta or Growth factor receptor-bound protein 4, Grb4) plays a crucial role in connecting signaling pathways of tyrosine kinase receptors and important effectors in actin dynamics and cytoskeletal remodeling. It binds neuronal signaling proteins such as ephrinB and Disabled-1 (Dab-1) exclusively. Nck adaptor proteins regulate actin cytoskeleton dynamics by linking proline-rich effector molecules to protein tyrosine kinases and phosphorylated signaling intermediates. They contain three SH3 domains and a C-terminal SH2 domain. They function downstream of the PDGFbeta receptor and are involved in Rho GTPase signaling and actin dynamics. Vertebrates contain two Nck adaptor proteins: Nck1 (also called Nckalpha) and Nck2, which show partly overlapping functions but also bind distinct targets. The second SH3 domain of Nck appears to prefer ligands containing the APxxPxR motif. SH3 domains are protein interaction domains that usually bind to proline-rich ligands with moderate affinity and selectivity, preferentially a PxxP motif. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212835 [Multi-domain] Cd Length: 55 Bit Score: 48.85 E-value: 3.28e-07

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....*
gi 1804876928 1079 AQVTSAYVASGSEQLSLAPGQLILILKKNSSGWWQGELQArgkkrQKGWFPASHV 1133
Cdd:cd11902      3 AFVKFAYVAEREDELSLVKGSRVTVMEKCSDGWWRGSYNG-----QIGWFPSNYV 52

Src Homology 3 domain of Src Kinase-Associated Phosphoprotein 1 and similar proteins; This subfamily is composed of SKAP1, SKAP2, and similar proteins. SKAP1 and SKAP2 are immune cell-specific adaptor proteins that play roles in T- and B-cell adhesion, respectively, and are thus important in the migration of T- and B-cells to sites of inflammation and for movement during T-cell conjugation with antigen-presenting cells. Both SKAP1 and SKAP2 bind to ADAP (adhesion and degranulation-promoting adaptor protein), among many other binding partners. They contain a pleckstrin homology (PH) domain, a C-terminal SH3 domain, and several tyrosine phosphorylation sites. The SH3 domain of SKAP1 is necessary for its ability to regulate T-cell conjugation with antigen-presenting cells and the formation of LFA-1 clusters. SKAP1 binds primarily to a proline-rich region of ADAP through its SH3 domain; its degradation is regulated by ADAP. A secondary interaction occurs via the ADAP SH3 domain and the RKxxYxxY motif in SKAP1. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212800 Cd Length: 53 Bit Score: 48.58 E-value: 3.33e-07

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|
gi 1804876928 1155 AMYDYVANNEDELNFSKGQLINVLNK--DDPDWWQGEINGVTGLFPSNYV 1202
Cdd:cd11866      4 GLWDCSGNEPDELSFKRGDLIYIISKeyDSFGWWVGELNGKVGLVPKDYL 53

Src Homology 3 domain of Bruton's tyrosine kinase; BTK is a cytoplasmic (or nonreceptor) tyr kinase containing Src homology protein interaction domains (SH3, SH2) N-terminal to the catalytic tyr kinase domain. It also contains an N-terminal pleckstrin homology (PH) domain, which binds the products of PI3K and allows membrane recruitment and activation, and the Tec homology (TH) domain with proline-rich and zinc-binding regions. Btk is expressed in B-cells, and a variety of myeloid cells including mast cells, platelets, neutrophils, and dendrictic cells. It interacts with a variety of partners, from cytosolic proteins to nuclear transcription factors, suggesting a diversity of functions. Stimulation of a diverse array of cell surface receptors, including antigen engagement of the B-cell receptor (BCR), leads to PH-mediated membrane translocation of Btk and subsequent phosphorylation by Src kinase and activation. Btk plays an important role in the life cycle of B-cells including their development, differentiation, proliferation, survival, and apoptosis. Mutations in Btk cause the primary immunodeficiency disease, X-linked agammaglobulinaemia (XLA) in humans. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212839 [Multi-domain] Cd Length: 55 Bit Score: 48.67 E-value: 3.40e-07

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|.
gi 1804876928 1153 VIAMYDYVANNEDELNFSKGQLINVLNKDDPDWWQG-EINGVTGLFPSNYV 1202
Cdd:cd11906      3 VVALYDYTPMNAQDLQLRKGEEYVILEESNLPWWRArDKNGREGYIPSNYV 53

Third Src Homology 3 domain of SH3 domain containing ring finger 1 (SH3RF1), SH3RF3, and similar domains; SH3RF1 (or POSH) and SH3RF3 (or POSH2) are scaffold proteins that function as E3 ubiquitin-protein ligases. They contain an N-terminal RING finger domain and four SH3 domains. This model represents the third SH3 domain, located in the middle of SH3RF1 and SH3RF3, and similar domains. SH3RF1 plays a role in calcium homeostasis through the control of the ubiquitin domain protein Herp. It may also have a role in regulating death receptor mediated and JNK mediated apoptosis. SH3RF3 interacts with p21-activated kinase 2 (PAK2) and GTP-loaded Rac1. It may play a role in regulating JNK mediated apoptosis in certain conditions. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212717 [Multi-domain] Cd Length: 55 Bit Score: 48.54 E-value: 3.52e-07

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....*
gi 1804876928 1007 YIALYSYSSVEPGDLTFIEGEEILVTQK--DGeWWTGS--IGDRTGIFPSNYVKP 1057
Cdd:cd11783      2 YVALYPYKPQKPDELELRKGEMYTVTEKcqDG-WFKGTslRTGQSGVFPGNYVQP 55

First Src Homology 3 domain of SH3 domain containing ring finger 3, an E3 ubiquitin-protein ligase; SH3RF3 is also called POSH2 (Plenty of SH3s 2) or SH3MD4 (SH3 multiple domains protein 4). It is a scaffold protein with E3 ubiquitin-protein ligase activity. It was identified in the screen for interacting partners of p21-activated kinase 2 (PAK2). It may play a role in regulating JNK mediated apoptosis in certain conditions. It also interacts with GTP-loaded Rac1. SH3RF3 is highly homologous to SH3RF1; it also contains an N-terminal RING finger domain and four SH3 domains. This model represents the first SH3 domain, located at the N-terminal half, of SH3RF3. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212861 Cd Length: 54 Bit Score: 48.38 E-value: 3.62e-07

                           10        20        30        40
                   ....*....|....*....|....*....|....*....|....*....
gi 1804876928 1009 ALYSYSSVEPGDLTFIEGEEILVTQK-DGEWWTGSIGDRTGIFPSNYVK 1056
Cdd:cd11928      5 ALYSYEGKEPGDLKFNKGDIIILRRKvDENWYHGELNGCHGFLPASYIQ 53

Src Homology 3 domain of Abelson helper integration site-1 (AHI-1); AHI-1, also called Jouberin, is expressed in high levels in the brain, gonad tissues, and skeletal muscle. It is an adaptor protein that interacts with the small GTPase Rab8a and regulates it distribution and function, affecting cilium formation and vesicle transport. Mutations in the AHI-1 gene can cause Joubert syndrome, a disorder characterized by brainstem malformations, cerebellar aplasia/hypoplasia, and retinal dystrophy. AHI-1 variation is also associated with susceptibility to schizophrenia and type 2 diabetes mellitus progression. AHI-1 contains WD40 and SH3 domains. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212746 [Multi-domain] Cd Length: 52 Bit Score: 48.28 E-value: 3.62e-07

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|
gi 1804876928 1008 IALYSYSSVEPGDLTFIEGEEILVTQKDGE-WWTGSIGD-RTGIFPSNYV 1055
Cdd:cd11812      3 VALYDYTANRSDELTIHRGDIIRVLYKDNDnWWFGSLVNgQQGYFPANYV 52

First Src Homology 3 domain of Sorbin and SH3 domain containing (Sorbs) proteins and similar domains; This family, also called the vinexin family, is composed predominantly of adaptor proteins containing one sorbin homology (SoHo) and three SH3 domains. Members include the first SH3 domains of Sorbs1 (or ponsin), Sorbs2 (or ArgBP2), Vinexin (or Sorbs3), and similar domains. They are involved in the regulation of cytoskeletal organization, cell adhesion, and growth factor signaling. Members of this family bind multiple partners including signaling molecules like c-Abl, c-Arg, Sos, and c-Cbl, as well as cytoskeletal molecules such as vinculin and afadin. They may have overlapping functions. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212715 [Multi-domain] Cd Length: 53 Bit Score: 48.49 E-value: 3.65e-07

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|...
gi 1804876928  923 KAQALCSWTAKKDNHLNFSKHDIITVLEQ-QENWWFGEVHGGRGWFPKSYVKI 974
Cdd:cd11781      1 KARALYPFKAQSAKELSLKKGDIIYIRRQiDKNWYEGEHNGRVGIFPASYVEI 53

Pleckstrin homology domain-containing family G member 7 pleckstrin homology (PH) domain; PLEKHG7 has a RhoGEF DH/double-homology domain in tandem with a PH domain which is involved in phospholipid binding. PLEKHG7 is proposed to functions as a guanine nucleotide exchange factor (GEF) and is involved in the regulation of Rho protein signal transduction. PH domains have diverse functions, but in general are involved in targeting proteins to the appropriate cellular location or in the interaction with a binding partner. They share little sequence conservation, but all have a common fold, which is electrostatically polarized. Less than 10% of PH domains bind phosphoinositide phosphates (PIPs) with high affinity and specificity. PH domains are distinguished from other PIP-binding domains by their specific high-affinity binding to PIPs with two vicinal phosphate groups: PtdIns(3,4)P2, PtdIns(4,5)P2 or PtdIns(3,4,5)P3 which results in targeting some PH domain proteins to the plasma membrane. A few display strong specificity in lipid binding. Any specificity is usually determined by loop regions or insertions in the N-terminus of the domain, which are not conserved across all PH domains. PH domains are found in cellular signaling proteins such as serine/threonine kinase, tyrosine kinases, regulators of G-proteins, endocytotic GTPases, adaptors, as well as cytoskeletal associated molecules and in lipid associated enzymes.

Pssm-ID: 270065 Cd Length: 128 Bit Score: 50.74 E-value: 3.75e-07

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                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1804876928 1455 KLLHSGKLYKTKSNK--ELHGFLFNDFLLLTYMVKQFAVSSGSEKLFS---------SKSNAQFKMYKTPIFLNEVLVK- 1522
Cdd:cd13245      1 QLLHEGPLTLIESGKtlDVYLFLFDDMLLITKMKKNLKKKKSSDSENSmpsleltplIKEGGSYTVYKQPIPLDRLCLHd 80

                           90       100       110       120
                   ....*....|....*....|....*....|....*....|....*...
gi 1804876928 1523 -LPTDPSSD--EPVFHISHIDR------VYTLRTDNINERTAWVQKIK 1561
Cdd:cd13245     81 vDPNEATANglKHAFVLVHLNRyqqvigVYTLQASSENTKQTWMSKLR 128

Src homology 3 domain of Protein kinase C and Casein kinase Substrate in Neurons 1 (PACSIN1) and PACSIN 2; PACSIN 1 or Syndapin I (Synaptic dynamin-associated protein I) is expressed specifically in the brain and is localized in neurites and synaptic boutons. It binds the brain-specific proteins dynamin I, synaptojanin, synapsin I, and neural Wiskott-Aldrich syndrome protein (nWASP), and functions as a link between the cytoskeletal machinery and synaptic vesicle endocytosis. PACSIN 1 interacts with huntingtin and may be implicated in the neuropathology of Huntington's disease. PACSIN 2 or Syndapin II is expressed ubiquitously and is involved in the regulation of tubulin polymerization. It associates with Golgi membranes and forms a complex with dynamin II which is crucial in promoting vesicle formation from the trans-Golgi network. PACSINs act as regulators of cytoskeletal and membrane dynamics. Vetebrates harbor three isoforms with distinct expression patterns and specific functions. PACSINs contain an N-terminal F-BAR domain and a C-terminal SH3 domain. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212931 [Multi-domain] Cd Length: 56 Bit Score: 48.41 E-value: 3.81e-07

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                   ....*....|....*....|....*....|....*....|....*....|....
gi 1804876928 1152 QVIAMYDYVANNEDELNFSKG-QLINVLNKDDPDWWQGEI-NGVTGLFPSNYVK 1203
Cdd:cd11998      2 RVRALYDYDGQEQDELSFKAGdELTKLEDEDEQGWCKGRLdSGQVGLYPANYVE 55

Src Homology 3 (SH3) domain of Inhibitor of ASPP protein (iASPP); iASPP, also called RelA-associated inhibitor (RAI), is an oncoprotein that inhibits the apoptotic transactivation potential of p53. It is upregulated in human breast cancers expressing wild-type p53, in acute leukemias regardless of the p53 mutation status, as well as in ovarian cancer where it is associated with poor patient outcome and chemoresistance. iASPP is also a binding partner and negative regulator of p65RelA, which promotes cell proliferation and inhibits apoptosis; p65RelA has the opposite effect on cell growth compared to the p53 family. It contains a proline-rich region, four ankyrin (ANK) repeats, and an SH3 domain at its C-terminal half. The SH3 domain and the ANK repeats of iASPP contribute to the p53 binding site; they bind to the DNA binding domain of p53. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212885 [Multi-domain] Cd Length: 56 Bit Score: 48.39 E-value: 3.87e-07

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                   ....*....|....*....|....*....|....*....|....*....
gi 1804876928 1009 ALYSYSSVEPGDLTFIEGEEILVTQKDGE---WWTGSIGDRTGIFPSNY 1054
Cdd:cd11952      5 ALWDYSAEFPDELSFKEGDMVTVLRKDGEgtdWWWASLCGREGYVPRNY 53

Src Homology 3 domain of Insulin Receptor tyrosine kinase Substrate p53, Brain-specific Angiogenesis Inhibitor 1-Associated Protein 2 (BAIAP2)-Like proteins, and similar proteins; Proteins in this family include IRSp53, BAIAP2L1, BAIAP2L2, and similar proteins. They all contain an Inverse-Bin/Amphiphysin/Rvs (I-BAR) or IMD domain in addition to the SH3 domain. IRSp53, also known as BAIAP2, is a scaffolding protein that takes part in many signaling pathways including Cdc42-induced filopodia formation, Rac-mediated lamellipodia extension, and spine morphogenesis. IRSp53 exists as multiple splicing variants that differ mainly at the C-termini. BAIAP2L1, also called IRTKS (Insulin Receptor Tyrosine Kinase Substrate), serves as a substrate for the insulin receptor and binds the small GTPase Rac. It plays a role in regulating the actin cytoskeleton and colocalizes with F-actin, cortactin, VASP, and vinculin. IRSp53 and IRTKS also mediate the recruitment of effector proteins Tir and EspFu, which regulate host cell actin reorganization, to bacterial attachment sites. BAIAP2L2 co-localizes with clathrin plaques but its function has not been determined. The SH3 domains of IRSp53 and IRTKS have been shown to bind the proline-rich C-terminus of EspFu. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212713 [Multi-domain] Cd Length: 57 Bit Score: 48.47 E-value: 4.02e-07

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                   ....*....|....*....|....*....|....*....|....*....|....*..
gi 1804876928  786 KALYRFEARSHDEMSFNSGDIIQVdekTIGEP--GWLYGSFQGN--FGWFPCNYVEK 838
Cdd:cd11779      4 KALYPHAAGGETQLSFEEGDVITL---LGPEPrdGWHYGENERSgrRGWFPIAYTEP 57

Fifth Src homology 3 domain (or SH3E) of Intersectin-2; Intersectin-2 (ITSN2) is an adaptor protein that functions in exo- and endocytosis, actin cytoskeletal reorganization, and signal transduction. It plays a role in clathrin-coated pit (CCP) formation. It binds to many proteins through its multidomain structure and facilitate the assembly of multimeric complexes. ITSN2 also functions as a specific GEF for Cdc42 activation in epithelial morphogenesis, and is required in mitotic spindle orientation. It exists in alternatively spliced short and long isoforms. The short isoform contains two Eps15 homology domains (EH1 and EH2), a coiled-coil region and five SH3 domains (SH3A-E), while the long isoform, in addition, contains RhoGEF (also called Dbl-homologous or DH), Pleckstrin homology (PH) and C2 domains. The fifth SH3 domain (or SH3E) of ITSN2 is expected to bind protein partners, similar to ITSN1 which has been shown to bind many protein partners including SGIP1, Sos1, dynamin1/2, CIN85, c-Cbl, SHIP2, N-WASP, and synaptojanin-1, among others. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212929 [Multi-domain] Cd Length: 54 Bit Score: 48.44 E-value: 4.07e-07

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                   ....*....|....*....|....*....|....*....|....*....|....*....|
gi 1804876928  916 GQVVenlkaqALCSWTAKKDNHLNFSKHDIITVLEQQE-NWWFGEVHGGRGWFPKSYVKI 974
Cdd:cd11996      1 CQVI------AMYDYTANNEDELSFSKGQLINVLNKDDpDWWQGEINGVTGLFPSNYVKM 54

Src homology 3 domain of Apoptosis Stimulating of p53 proteins (ASPP); The ASPP family of proteins bind to important regulators of apoptosis (p53, Bcl-2, and RelA) and cell growth (APCL, PP1). They share similarity at their C-termini, where they harbor a proline-rich region, four ankyrin (ANK) repeats, and an SH3 domain. Vertebrates contain three members of the family: ASPP1, ASPP2, and iASPP. ASPP1 and ASPP2 activate the apoptotic function of the p53 family of tumor suppressors (p53, p63, and p73), while iASPP is an oncoprotein that specifically inhibits p53-induced apoptosis. The expression of ASPP proteins is altered in tumors; ASPP1 and ASPP2 are downregulated whereas iASPP is upregulated is some cancer types. ASPP proteins also bind and regulate protein phosphatase 1 (PP1), and this binding is competitive with p53 binding. The SH3 domain and the ANK repeats of ASPP contribute to the p53 binding site; they bind to the DNA binding domain of p53. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212741 [Multi-domain] Cd Length: 57 Bit Score: 48.53 E-value: 4.26e-07

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                   ....*....|....*....|....*....|....*....|....*....|
gi 1804876928 1009 ALYSYSSVEPGDLTFIEGEEILVTQKDG----EWWTGSIGDRTGIFPSNY 1054
Cdd:cd11807      5 ALFDYEAENGDELSFREGDELTVLRKGDddetEWWWARLNDKEGYVPRNL 54

Third (or C-terminal) Src Homology 3 domain of Sorbin and SH3 domain containing 1 (Sorbs1), also called ponsin; Sorbs1 is also called ponsin, SH3P12, or CAP (c-Cbl associated protein). It is an adaptor protein containing one sorbin homology (SoHo) and three SH3 domains. It binds Cbl and plays a major role in regulating the insulin signaling pathway by enhancing insulin-induced phosphorylation of Cbl. Sorbs1, like vinexin, localizes at cell-ECM and cell-cell adhesion sites where it binds vinculin, paxillin, and afadin. It may function in the control of cell motility. Other interaction partners of Sorbs1 include c-Abl, Sos, flotillin, Grb4, ataxin-7, filamin C, among others. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212849 [Multi-domain] Cd Length: 59 Bit Score: 48.45 E-value: 4.42e-07

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                   ....*....|....*....|....*....|....*....|....*....|....*...
gi 1804876928  782 LVNYKALYRFEARSHDEMSFNSGDIIQVDEKTigEPGWLYGSFQGN--FGWFPCNYVE 837
Cdd:cd11916      1 AYSYQALYSYAPQNDDELELRDGDIVDVMEKC--DDGWFVGTSRRTkqFGTFPGNYVK 56

Src Homology 3 domain of GTPase Regulator Associated with Focal adhesion kinase 2; GRAF2, also called Rho GTPase activating protein 10 (ARHGAP10) or PS-GAP, is a GAP with activity towards Cdc42 and RhoA. It regulates caspase-activated p21-activated protein kinase-2 (PAK-2p34). GRAF2 interacts with PAK-2p34, leading to its stabilization and decrease of cell death. It is highly expressed in skeletal muscle, and is involved in alpha-catenin recruitment at cell-cell junctions. GRAF2 contains an N-terminal BAR domain, followed by a Pleckstrin homology (PH) domain, a Rho GAP domain, and a C-terminal SH3 domain. The SH3 domain of GRAF binds PKNbeta, a target of the small GTPase Rho. SH3 domains bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs; they play a role in the regulation of enzymes by intramolecular interactions, changing the subcellular localization of signal pathway components and mediate multiprotein complex assemblies.

Pssm-ID: 212998 [Multi-domain] Cd Length: 54 Bit Score: 48.06 E-value: 4.60e-07

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                   ....*....|....*....|....*....|....*....|....*....|..
gi 1804876928  786 KALYRFEARSHDEMSFNSGDIIQvDEKTIGEPGWLYGSFQGNFGWFPCNYVE 837
Cdd:cd12065      3 KAVYPCEAEHSSELSFEVGAIFE-DVTLSREPGWLEGTLNGKRGLIPENYVE 53

First Src Homology 3 domain of Sorbin and SH3 domain containing 2 (Sorbs2), also called Arg-binding protein 2 (ArgBP2); Sorbs2 or ArgBP2 is an adaptor protein containing one sorbin homology (SoHo) and three SH3 domains. It regulates actin-dependent processes including cell adhesion, morphology, and migration. It is expressed in many tissues and is abundant in the heart. Like vinexin, it is found in focal adhesion where it interacts with vinculin and afadin. It also localizes in epithelial cell stress fibers and in cardiac muscle cell Z-discs. Sorbs2 has been implicated to play roles in the signaling of c-Arg, Akt, and Pyk2. Other interaction partners of Sorbs2 include c-Abl, flotillin, spectrin, dynamin 1/2, synaptojanin, PTP-PEST, among others. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212853 [Multi-domain] Cd Length: 55 Bit Score: 48.08 E-value: 4.64e-07

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....
gi 1804876928  786 KALYRFEARSHDEMSFNSGDIIQVDEKTigEPGWLYGSFQGNFGWFPCNYVEKM 839
Cdd:cd11920      4 RAVYDFKAQTSKELSFKKGDTVYILRKI--DQNWYEGEHHGRVGIFPISYVEKL 55

Src Homology 3 domain of Nephrocystin (or Nephrocystin-1); Nephrocystin contains an SH3 domain involved in signaling pathways that regulate cell adhesion and cytoskeletal organization. It is a protein that in humans is associated with juvenile nephronophthisis, an inherited kidney disease characterized by renal fibrosis that lead to chronic renal failure in children. It is localized in cell-cell junctions in renal duct cells, and is known to interact with Ack1, an activated Cdc42-associated kinase. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212704 [Multi-domain] Cd Length: 54 Bit Score: 48.08 E-value: 4.69e-07

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                   ....*....|....*....|....*....|....*....|....*....|....*.
gi 1804876928 1006 EYIALYSYSSVEPGDLTFIEGE--EILVTQKDGeWWTG--SIGDRtGIFPSNYVKP 1057
Cdd:cd11770      1 LYEALSDFQAEQEGDLSFKKGEvlRIISKRADG-WWLAenSKGNR-GLVPKTYLKV 54

C-terminal Src Homology 3 domain of Nebulette and LIM-nebulette (or Lasp2); Nebulette is a cardiac-specific protein that localizes to the Z-disc. It interacts with tropomyosin and is important in stabilizing actin thin filaments in cardiac muscles. Polymorphisms in the nebulette gene are associated with dilated cardiomyopathy, with some mutations resulting in severe heart failure. Nebulette is a 107kD protein that contains an N-terminal acidic region, multiple nebulin repeats, and a C-terminal SH3 domain. LIM-nebulette, also called Lasp2 (LIM and SH3 domain protein 2), is an alternatively spliced variant of nebulette. Although it shares a gene with nebulette, Lasp2 is not transcribed from a muscle-specific promoter, giving rise to its multiple tissue expression pattern with highest amounts in the brain. It can crosslink actin filaments and it affects cell spreading. Lasp2 is a 34kD protein containing an N-terminal LIM domain, three nebulin repeats, and a C-terminal SH3 domain. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212868 [Multi-domain] Cd Length: 58 Bit Score: 48.46 E-value: 4.71e-07

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                   ....*....|....*....|....*....|....*....|....*....|..
gi 1804876928 1155 AMYDYVANNEDELNFSKGQLINVLNKDDPDWWQGEI--NGVTGLFPSNYVKM 1204
Cdd:cd11935      5 AMYDYSAQDEDEVSFRDGDYIVNVQPIDEGWMYGTVqrTGRTGMLPANYIEF 56

Second Src Homology 3 domain of Bzz1 and similar domains; Bzz1 (or Bzz1p) is a WASP/Las17-interacting protein involved in endocytosis and trafficking to the vacuole. It physically interacts with type I myosins and functions in the early steps of endocytosis. Together with other proteins, it induces membrane scission in yeast. Bzz1 contains an N-terminal F-BAR (FES-CIP4 Homology and Bin/Amphiphysin/Rvs), a central coiled-coil, and two C-terminal SH3 domains. This model represents the second C-terminal SH3 domain. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212712 [Multi-domain] Cd Length: 51 Bit Score: 48.26 E-value: 4.74e-07

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|
gi 1804876928  786 KALYRFEARSHDEMSFNSGDIIQVDEKTIGEpGWLYGSFQGNFGWFPCNY 835
Cdd:cd11778      3 EALYDYEAQGDDEISIRVGDRIAVIRGDDGS-GWTYGEINGVKGLFPTSY 51

chromosome segregation protein SMC, primarily archaeal type; SMC (structural maintenance of chromosomes) proteins bind DNA and act in organizing and segregating chromosomes for partition. SMC proteins are found in bacteria, archaea, and eukaryotes. It is found in a single copy and is homodimeric in prokaryotes, but six paralogs (excluded from this family) are found in eukarotes, where SMC proteins are heterodimeric. This family represents the SMC protein of archaea and a few bacteria (Aquifex, Synechocystis, etc); the SMC of other bacteria is described by TIGR02168. The N- and C-terminal domains of this protein are well conserved, but the central hinge region is skewed in composition and highly divergent. [Cellular processes, Cell division, DNA metabolism, Chromosome-associated proteins]

Pssm-ID: 274009 [Multi-domain] Cd Length: 1164 Bit Score: 55.07 E-value: 4.78e-07

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1804876928  427 REAERKAQKEKEEWERKQRELQEqewkkqleLEKRLEkqreleRQReEERRKEIERREAAKQELER-QRRLEWERIRRQE 505
Cdd:TIGR02169  663 RGGILFSRSEPAELQRLRERLEG--------LKRELS------SLQ-SELRRIENRLDELSQELSDaSRKIGEIEKEIEQ 727

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1804876928  506 LLNQRNREQEEIVRLNSKKKSLHLELEALNGKHQQISGRLQDVRLRKQTQKTEIEVLDKQCDLEimEIKQLQQE------ 579
Cdd:TIGR02169  728 LEQEEEKLKERLEELEEDLSSLEQEIENVKSELKELEARIEELEEDLHKLEEALNDLEARLSHS--RIPEIQAElsklee 805

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1804876928  580 --------LQDYQNKLIYLVPEKQLLNERIKNMQlgntpDLGIDL-LHKKSLEKE-ELCQRLKEQLDALEKETASKLSEM 649
Cdd:TIGR02169  806 evsriearLREIEQKLNRLTLEKEYLEKEIQELQ-----EQRIDLkEQIKSIEKEiENLNGKKEELEEELEELEAALRDL 880

                          250       260       270       280       290       300       310       320
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1804876928  650 DSFNNQLKcGNMDDSVLQcllsllsclnnlfllLKELRESYNTQQLALEQlhkiKRDKLKEIERKRSEL------IQKKK 723
Cdd:TIGR02169  881 ESRLGDLK-KERDELEAQ---------------LRELERKIEELEAQIEK----KRKRLSELKAKLEALeeelseIEDPK 940

                          330       340       350       360       370       380
                   ....*....|....*....|....*....|....*....|....*....|....*....|...
gi 1804876928  724 LEDEAIRKAKQGKENLWRESLRKEE----------------EEKQKRLQEEKTQEKVQEEERK 770
Cdd:TIGR02169  941 GEDEEIPEEELSLEDVQAELQRVEEeiralepvnmlaiqeyEEVLKRLDELKEKRAKLEEERK 1003

phosphodiesterase; Provisional

Pssm-ID: 237177 [Multi-domain] Cd Length: 520 Bit Score: 54.40 E-value: 4.82e-07

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1804876928  687 RESYNTQQLAL----EQLHKIKRDKLKEIERKRSELiqkKKLEdeaiRKAKQGKENLWR--ESLRKEEEEKQKRLQE-EK 759
Cdd:PRK12704    49 KEAEAIKKEALleakEEIHKLRNEFEKELRERRNEL---QKLE----KRLLQKEENLDRklELLEKREEELEKKEKElEQ 121

                           90       100       110
                   ....*....|....*....|....*....|....*.
gi 1804876928  760 TQEKVQEEERKVEEKQCEPASALVNYKALYRFEARS 795
Cdd:PRK12704   122 KQQELEKKEEELEELIEEQLQELERISGLTAEEAKE 157

Src homology 3 domain of Cortactin and related proteins; This subfamily includes cortactin, Abp1 (actin-binding protein 1), hematopoietic lineage cell-specific protein 1 (HS1), and similar proteins. These proteins are involved in regulating actin dynamics through direct or indirect interaction with the Arp2/3 complex, which is required to initiate actin polymerization. They all contain at least one C-terminal SH3 domain. Cortactin and HS1 bind Arp2/3 and actin through an N-terminal region that contains an acidic domain and several copies of a repeat domain found in cortactin and HS1. Abp1 binds actin via an N-terminal actin-depolymerizing factor (ADF) homology domain. Yeast Abp1 binds Arp2/3 directly through two acidic domains. Mammalian Abp1 does not directly interact with Arp2/3; instead, it regulates actin dynamics indirectly by interacting with dynamin and WASP family proteins. The C-terminal region of these proteins acts as an adaptor or scaffold that can connect membrane trafficking and signaling proteins that bind the SH3 domain within the actin network. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212753 [Multi-domain] Cd Length: 54 Bit Score: 48.08 E-value: 5.02e-07

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|...
gi 1804876928  924 AQALCSWTAKKDNHLNFSKHDIITVLEQ-QENWWFGEVHGG-RGWFPKSYVKI 974
Cdd:cd11819      2 AKALYDYQAAEDNEISFVEGDIITQIEQiDEGWWLGVNAKGqKGLFPANYVEL 54

Src Homology 3 domain of Insulin Receptor tyrosine kinase Substrate p53, Brain-specific Angiogenesis Inhibitor 1-Associated Protein 2 (BAIAP2)-Like proteins, and similar proteins; Proteins in this family include IRSp53, BAIAP2L1, BAIAP2L2, and similar proteins. They all contain an Inverse-Bin/Amphiphysin/Rvs (I-BAR) or IMD domain in addition to the SH3 domain. IRSp53, also known as BAIAP2, is a scaffolding protein that takes part in many signaling pathways including Cdc42-induced filopodia formation, Rac-mediated lamellipodia extension, and spine morphogenesis. IRSp53 exists as multiple splicing variants that differ mainly at the C-termini. BAIAP2L1, also called IRTKS (Insulin Receptor Tyrosine Kinase Substrate), serves as a substrate for the insulin receptor and binds the small GTPase Rac. It plays a role in regulating the actin cytoskeleton and colocalizes with F-actin, cortactin, VASP, and vinculin. IRSp53 and IRTKS also mediate the recruitment of effector proteins Tir and EspFu, which regulate host cell actin reorganization, to bacterial attachment sites. BAIAP2L2 co-localizes with clathrin plaques but its function has not been determined. The SH3 domains of IRSp53 and IRTKS have been shown to bind the proline-rich C-terminus of EspFu. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212713 [Multi-domain] Cd Length: 57 Bit Score: 48.09 E-value: 5.24e-07

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....*
gi 1804876928  923 KAQALCSWTAKKDNHLNFSKHDIITVL--EQQENWWFGE--VHGGRGWFPKSYVK 973
Cdd:cd11779      2 RVKALYPHAAGGETQLSFEEGDVITLLgpEPRDGWHYGEneRSGRRGWFPIAYTE 56

C-terminal Src Homology 3 domain of NADPH oxidase activator 1; Noxa1 is a homolog of p67phox and is a cytosolic subunit of the nonphagocytic NADPH oxidase complex Nox1, which catalyzes the transfer of electrons from NADPH to molecular oxygen to form superoxide. Noxa1 is co-expressed with Nox1 in colon, stomach, uterus, prostate, and vascular smooth muscle cells, consistent with its regulatory role. It does not interact with p40phox, unlike p67phox, making Nox1 activity independent of p40phox, unlike Nox2. Noxa1 contains TPR, PB1, and C-terminal SH3 domains, but lacks the central SH3 domain that is present in p67phox. The TPR domain binds activated GTP-bound Rac. The C-terminal SH3 domain binds the polyproline motif found at the C-terminus of Noxo1, a homolog of p47phox. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212980 Cd Length: 53 Bit Score: 47.89 E-value: 5.24e-07

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|.
gi 1804876928 1008 IALYSYSSVEPGDLTFIEGEEI-LVTQKDGEWWTGSIGDRTGIFPSNYVKP 1057
Cdd:cd12047      3 VAQHDYSAQGPEDLEFSQGDTIdILSEVNQEWLEGHCDGRIGIFPKCFAVR 53

C-terminal Src Homology 3 domain of LIM and SH3 domain protein 1; Lasp1 is a cytoplasmic protein that binds focal adhesion proteins and is involved in cell signaling, migration, and proliferation. It is overexpressed in several cancer cells including breast, ovarian, bladder, and liver. In cancer cells, it can be found in the nucleus; its degree of nuclear localization correlates with tumor size and poor prognosis. Lasp1 is a 36kD protein containing an N-terminal LIM domain, two nebulin repeats, and a C-terminal SH3 domain. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212867 [Multi-domain] Cd Length: 59 Bit Score: 48.07 E-value: 5.52e-07

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|.
gi 1804876928 1155 AMYDYVANNEDELNFSKGQLINVLNKDDPDWWQG--EINGVTGLFPSNYVK 1203
Cdd:cd11934      7 AVYDYNAADEDEVSFQDGDTIVNVQQIDDGWMYGtvERTGDTGMLPANYVE 57

C-terminal Src homology 3 domain of GRB2-related adaptor protein; GRAP is a GRB-2 like adaptor protein that is highly expressed in lymphoid tissues. It acts as a negative regulator of T cell receptor (TCR)-induced lymphocyte proliferation by downregulating the signaling to the Ras/ERK pathway. It has been identified as a regulator of TGFbeta signaling in diabetic kidney tubules and may have a role in the pathogenesis of the disease. GRAP contains an N-terminal SH3 domain, a central SH2 domain, and a C-terminal SH3 domain. The C-terminal SH3 domains (SH3c) of the related proteins, GRB2 and GRAP2, have been shown to bind to classical PxxP motif ligands, as well as to non-classical motifs. GRB2 SH3c binds Gab2 (Grb2-associated binder 2) through epitopes containing RxxK motifs, while the SH3c of GRAP2 binds to the phosphatase-like protein HD-PTP via a RxxxxK motif. SH3 domains are protein interaction domains that typically bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212884 Cd Length: 53 Bit Score: 47.87 E-value: 5.52e-07

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|
gi 1804876928  924 AQALCSWTAKKDNHLNFSKHDIITVLEQQE-NWWFGEVHGGRGWFPKSYV 972
Cdd:cd11951      2 VQAQYDFSAEDPSQLSFRRGDIIEVLDCPDpNWWRGRISGRVGFFPRNYV 51

First Src Homology 3 domain of SH3 domain containing ring finger protein 1, an E3 ubiquitin-protein ligase; SH3RF1 is also called POSH (Plenty of SH3s) or SH3MD2 (SH3 multiple domains protein 2). It is a scaffold protein that acts as an E3 ubiquitin-protein ligase. It plays a role in calcium homeostasis through the control of the ubiquitin domain protein Herp. It may also have a role in regulating death receptor mediated and JNK mediated apoptosis. SH3RF1 also enhances the ubiquitination of ROMK1 potassium channel resulting in its increased endocytosis. It contains an N-terminal RING finger domain and four SH3 domains. This model represents the first SH3 domain, located at the N-terminal half, of SH3RF1. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212860 Cd Length: 54 Bit Score: 48.02 E-value: 5.85e-07

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|..
gi 1804876928  924 AQALCSWTAKKDNHLNFSKHDIITVLEQ-QENWWFGEVHGGRGWFPKSYVKI 974
Cdd:cd11927      3 AKALYNYEGKEPGDLKFSKGDIIILRRQvDENWYHGEVNGIHGFFPTNFVQI 54

Src homology 3 domain of ephexin-1-like SH3 domain containing Rho guanine nucleotide exchange factors; Members of this family contain RhoGEF (also called Dbl-homologous or DH), Pleckstrin Homology (PH), and C-terminal SH3 domains. They include the Rho guanine nucleotide exchange factors ARHGEF5, ARHGEF16, ARHGEF19, ARHGEF26, ARHGEF27 (also called ephexin-1), and similar proteins, and are also called ephexins because they interact directly with ephrin A receptors. GEFs interact with Rho GTPases via their DH domains to catalyze nucleotide exchange by stabilizing the nucleotide-free GTPase intermediate. They play important roles in neuronal development. The SH3 domains of ARHGEFs play an autoinhibitory role through intramolecular interactions with a proline-rich region N-terminal to the DH domain. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212727 [Multi-domain] Cd Length: 55 Bit Score: 48.10 E-value: 5.93e-07

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|...
gi 1804876928  787 ALYRFEARSHDEMSFNSGDIIQVDEKTigEPGWLYGS--FQGNFGWFPCNYVE 837
Cdd:cd11793      4 CVHAYTAQQPDELTLEEGDVVNVLRKM--PDGWYEGErlRDGERGWFPSSYTE 54

Src homology 3 domain of Yes Protein Tyrosine Kinase; Yes (or c-Yes) is a member of the Src subfamily of proteins, which are cytoplasmic (or non-receptor) PTKs. c-Yes kinase is the cellular homolog of the oncogenic protein (v-Yes) encoded by the Yamaguchi 73 and Esh sarcoma viruses. It displays functional overlap with other Src subfamily members, particularly Src. It also shows some unique functions such as binding to occludins, transmembrane proteins that regulate extracellular interactions in tight junctions. Yes also associates with a number of proteins in different cell types that Src does not interact with, like JAK2 and gp130 in pre-adipocytes, and Pyk2 in treated pulmonary vein endothelial cells. Although the biological function of Yes remains unclear, it appears to have a role in regulating cell-cell interactions and vesicle trafficking in polarized cells. Src kinases contain an N-terminal SH4 domain with a myristoylation site, followed by SH3 and SH2 domains, a tyr kinase domain, and a regulatory C-terminal region containing a conserved tyr. They are activated by autophosphorylation at the tyr kinase domain, but are negatively regulated by phosphorylation at the C-terminal tyr by Csk (C-terminal Src Kinase). The SH3 domain of Src kinases contributes to substrate recruitment by binding adaptor proteins/substrates, and regulation of kinase activity through an intramolecular interaction. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212940 [Multi-domain] Cd Length: 58 Bit Score: 48.11 E-value: 6.37e-07

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....*.
gi 1804876928 1007 YIALYSYSSVEPGDLTFIEGEEI-LVTQKDGEWWTG-SIGD-RTGIFPSNYVKPKD 1059
Cdd:cd12007      3 FVALYDYEARTTEDLSFKKGERFqIINNTEGDWWEArSIATgKNGYIPSNYVAPAD 58

Src homology 3 domain of Ysc84p and similar fungal proteins; This family is composed of the Saccharomyces cerevisiae proteins, Ysc84p (also called LAS17-binding protein 4, Lsb4p) and Lsb3p, and similar fungal proteins. They contain an N-terminal SYLF domain (also called DUF500) and a C-terminal SH3 domain. Ysc84p localizes to actin patches and plays an important in actin polymerization during endocytosis. The N-terminal domain of both Ysc84p and Lsb3p can bind and bundle actin filaments. A study of the yeast SH3 domain interactome predicts that the SH3 domains of Lsb3p and Lsb4p may function as molecular hubs for the assembly of endocytic complexes. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212776 [Multi-domain] Cd Length: 55 Bit Score: 47.80 E-value: 6.53e-07

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....*
gi 1804876928  923 KAQALCSWTAKKDNHLNFSKHDIITVLEQ---QENWWFGEVHGGRGWFPKSYVKI 974
Cdd:cd11842      1 KAVALYDFAGEQPGDLAFQKGDIITILKKsdsQNDWWTGRIGGREGIFPANYVEL 55

Second Src Homology 3 domain (SH3B) of CD2-associated protein; CD2AP, also called CMS (Cas ligand with Multiple SH3 domains) or METS1 (Mesenchyme-to-Epithelium Transition protein with SH3 domains), is a cytosolic adaptor protein that plays a role in regulating the cytoskeleton. It is critical in cell-to-cell union necessary for kidney function. It also stabilizes the contact between a T cell and antigen-presenting cells. It is primarily expressed in podocytes at the cytoplasmic face of the slit diaphragm and serves as a linker anchoring podocin and nephrin to the actin cytoskeleton. CD2AP contains three SH3 domains, a proline-rich region, and a C-terminal coiled-coil domain. All of these domains enable CD2AP to bind various protein partners and assemble complexes that have been implicated in many different functions. This alignment model represents the second SH3 domain (SH3B) of CD2AP. SH3B binds to c-Cbl in a site (TPSSRPLR is the core binding motif) distinct from the c-Cbl/SH3A binding site. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212987 [Multi-domain] Cd Length: 55 Bit Score: 47.65 E-value: 6.55e-07

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....
gi 1804876928  786 KALYRFEARSHDEMSFNSGDIIQVDEKTigEPGWLYGSFQGNFGWFPCNYVEKM 839
Cdd:cd12054      4 KVLFEYVPQNEDELELKVGDIIDINEEV--EEGWWSGTLNGKSGLFPSNFVKEL 55

Src homology 3 domain of Phospholipase C (PLC) gamma 1; PLCgamma1 is widely expressed and is essential in growth and development. It is activated by the TrkA receptor tyrosine kinase and functions as a key regulator of cell differentiation. It is also the predominant PLCgamma in T cells and is required for T cell and NK cell function. PLCs catalyze the hydrolysis of phosphatidylinositol (4,5)-bisphosphate [PtdIns(4,5)P2] to produce Ins(1,4,5)P3 and diacylglycerol (DAG). Ins(1,4,5)P3 initiates the calcium signaling cascade while DAG functions as an activator of PKC. PLCgamma contains a Pleckstrin homology (PH) domain followed by an elongation factor (EF) domain, two catalytic regions of PLC domains that flank two tandem SH2 domains, followed by a SH3 domain and C2 domain. The SH3 domain of PLCgamma1 directly interacts with dynamin-1 and can serve as a guanine nucleotide exchange factor (GEF). It also interacts with Cbl, inhibiting its phosphorylation and activity. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212903 Cd Length: 60 Bit Score: 48.06 E-value: 7.21e-07

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....*
gi 1804876928  786 KALYRFEARSHDEMSFNSGDIIQVDEKTIGepGWLYGSFQGNFG-WFPCNYVEKM 839
Cdd:cd11970      7 KALFDYKAQREDELTFTKNAIIQNVEKQEG--GWWRGDYGGKKQlWFPSNYVEEI 59

Src homology 3 domain of Signal Transducing Adaptor Molecule 1; STAM1 is part of the endosomal sorting complex required for transport (ESCRT-0) and is involved in sorting ubiquitinated cargo proteins from the endosome. It may also be involved in the regulation of IL2 and GM-CSF mediated signaling, and has been implicated in neural cell survival. STAMs were discovered as proteins that are highly phosphorylated following cytokine and growth factor stimulation. They function in cytokine signaling and surface receptor degradation, as well as regulate Golgi morphology. They associate with many proteins including Jak2 and Jak3 tyrosine kinases, Hrs, AMSH, and UBPY. STAM adaptor proteins contain VHS (Vps27, Hrs, STAM homology), ubiquitin interacting (UIM), and SH3 domains. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212897 [Multi-domain] Cd Length: 55 Bit Score: 47.64 E-value: 7.39e-07

                           10        20        30        40
                   ....*....|....*....|....*....|....*....|....*...
gi 1804876928 1009 ALYSYSSVEPGDLTFIEGEEI-LVTQKDGEWWTGSIGDRTGIFPSNYV 1055
Cdd:cd11964      5 AIYDFEAAEDNELTFKAGDIItILDDSDPNWWKGETPQGTGLFPSNFV 52

Caldesmon;

Pssm-ID: 460421 [Multi-domain] Cd Length: 495 Bit Score: 53.72 E-value: 7.43e-07

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1804876928  412 VELEKRRQAlmeqqqREaERKAQKEKEEWERKQRELQEQEWKKQLELEKRLEKQRELERQREEERRKEIerreaAKQELE 491
Cdd:pfam02029    7 AARERRRRA------RE-ERRRQKEEEEPSGQVTESVEPNEHNSYEEDSELKPSGQGGLDEEEAFLDRT-----AKREER 74

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1804876928  492 RQRRLEwERIRRQELLNQRNreQEEIVRLNSKKKSLHLELEALNGKHQQISGRLQDVrlrkQTQKTEIEVLDKQCDLEIM 571
Cdd:pfam02029   75 RQKRLQ-EALERQKEFDPTI--ADEKESVAERKENNEEEENSSWEKEEKRDSRLGRY----KEEETEIREKEYQENKWST 147

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1804876928  572 EIKQLQQELQDyqnkliylVPEKQLLNERIKnmqlgntpdlgidllhKKSLEKEELCQRLKEQLDALEKETASKLSEMDS 651
Cdd:pfam02029  148 EVRQAEEEGEE--------EEDKSEEAEEVP----------------TENFAKEEVKDEKIKKEKKVKYESKVFLDQKRG 203

                          250       260       270       280       290       300       310       320
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1804876928  652 FNNQlKCGNMDDSVLQCLLSLLSCLNNlfLLLKELRESYNTQQLALEQ-LHKIKRdKLKEIERKRSELIQKKKLEDEA-I 729
Cdd:pfam02029  204 HPEV-KSQNGEEEVTKLKVTTKRRQGG--LSQSQEREEEAEVFLEAEQkLEELRR-RRQEKESEEFEKLRQKQQEAELeL 279

                          330       340       350       360       370
                   ....*....|....*....|....*....|....*....|....*....|....*
gi 1804876928  730 RKAKQGKEnlWRESLRkeEEEKQKRLQEEKTQEKVQEEERK-----VEEKQCEPA 779
Cdd:pfam02029  280 EELKKKRE--ERRKLL--EEEEQRRKQEEAERKLREEEEKRrmkeeIERRRAEAA 330

Fifth Src homology 3 domain (or SH3E) of Intersectin-1; Intersectin-1 (ITSN1) is an adaptor protein that functions in exo- and endocytosis, actin cytoskeletal reorganization, and signal transduction. It plays a role in clathrin-coated pit (CCP) formation. It binds to many proteins through its multidomain structure and facilitate the assembly of multimeric complexes. ITSN1 localizes in membranous organelles, CCPs, the Golgi complex, and may be involved in the cell membrane trafficking system. It exists in alternatively spliced short and long isoforms. The short isoform contains two Eps15 homology domains (EH1 and EH2), a coiled-coil region and five SH3 domains (SH3A-E), while the long isoform, in addition, contains RhoGEF (also called Dbl-homologous or DH), Pleckstrin homology (PH) and C2 domains. The fifth SH3 domain (or SH3E) of ITSN1 has been shown to bind many protein partners including SGIP1, Sos1, dynamin1/2, CIN85, c-Cbl, SHIP2, N-WASP, and synaptojanin-1, among others. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212928 [Multi-domain] Cd Length: 54 Bit Score: 47.64 E-value: 7.46e-07

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|..
gi 1804876928 1006 EYIALYSYSSVEPGDLTFIEGEEI-LVTQKDGEWWTGSIGDRTGIFPSNYVK 1056
Cdd:cd11995      2 QVIGMYDYTAQNDDELAFSKGQIInVLNKEDPDWWKGELNGQVGLFPSNYVK 53

Src homology 3 domain of Growth Arrest Specific protein 7; GAS7 is mainly expressed in the brain and is required for neurite outgrowth. It may also play a role in the protection and migration of embryonic stem cells. Treatment-related acute myeloid leukemia (AML) has been reported resulting from mixed-lineage leukemia (MLL)-GAS7 translocations as a complication of primary cancer treatment. GAS7 contains an N-terminal SH3 domain, followed by a WW domain, and a central F-BAR domain. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212763 [Multi-domain] Cd Length: 52 Bit Score: 47.51 E-value: 7.93e-07

                           10        20        30
                   ....*....|....*....|....*....|....*.
gi 1804876928  938 LNFSKHDIITVLEQQEN-WWFGEVHGGRGWFPKSYV 972
Cdd:cd11829     17 LSFEAGELIRVLQAPDGgWWEGEKDGLRGWFPASYV 52

Src Homology 3 domain of Mixed Lineage Kinase 4; MLK4 is a Serine/Threonine Kinase (STK), catalyzing the transfer of the gamma-phosphoryl group from ATP to S/T residues on protein substrates. MLKs act as mitogen-activated protein kinase kinase kinases (MAP3Ks, MKKKs, MAPKKKs), which phosphorylate and activate MAPK kinases (MAPKKs or MKKs or MAP2Ks), which in turn phosphorylate and activate MAPKs during signaling cascades that are important in mediating cellular responses to extracellular signals. MLKs play roles in immunity and inflammation, as well as in cell death, proliferation, and cell cycle regulation. The specific function of MLK4 is yet to be determined. Mutations in the kinase domain of MLK4 have been detected in colorectal cancers. MLK4 contains an SH3 domain, a catalytic kinase domain, a leucine zipper, a proline-rich region, and a CRIB domain that mediates binding to GTP-bound Cdc42 and Rac. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212991 [Multi-domain] Cd Length: 58 Bit Score: 47.63 E-value: 7.96e-07

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....*..
gi 1804876928 1007 YIALYSYSSVEPGDLTFIEGEEILVTQKDGE------WWTGSIGDRTGIFPSNYVKP 1057
Cdd:cd12058      2 WTALYDYEASGEDELSLRRGDVVEVLSQDAAvsgddgWWAGKIRHRLGIFPANYVTR 58

Second Src homology 3 domain of Tyrosine kinase substrate (Tks) proteins; Tks proteins are Src substrates and scaffolding proteins that play important roles in the formation of podosomes and invadopodia, the dynamic actin-rich structures that are related to cell migration and cancer cell invasion. Vertebrates contain two Tks proteins, Tks4 (Tyr kinase substrate with four SH3 domains) and Tks5 (Tyr kinase substrate with five SH3 domains), which display partially overlapping but non-redundant functions. Both associate with the ADAMs family of transmembrane metalloproteases, which function as sheddases and mediators of cell and matrix interactions. Tks5 interacts with N-WASP and Nck, while Tks4 is essential for the localization of MT1-MMP (membrane-type 1 matrix metalloproteinase) to invadopodia. Tks proteins contain an N-terminal Phox homology (PX) domain and four or five SH3 domains. This model characterizes the second SH3 domain of Tks proteins. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212949 Cd Length: 54 Bit Score: 47.45 E-value: 8.02e-07

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....
gi 1804876928  785 YKALYRFEARSHDEMSFNSGDIIQVDEKTIgePGWLYGSFQGNFGWFPCNYVEK 838
Cdd:cd12016      3 YITTQAYKAENEDEIGFETGVVVEVIQKNL--DGWWKIRYQGKEGWAPATYLKK 54

Second Src homology 3 domain of Tyrosine kinase substrate with four SH3 domains; Tks4, also called SH3 and PX domain-containing protein 2B (SH3PXD2B) or HOFI, is a Src substrate and scaffolding protein that plays an important role in the formation of podosomes and invadopodia, the dynamic actin-rich structures that are related to cell migration and cancer cell invasion. It is required in the formation of functional podosomes, EGF-induced membrane ruffling, and lamellipodia generation. It plays an important role in cellular attachment and cell spreading. Tks4 is essential for the localization of MT1-MMP (membrane-type 1 matrix metalloproteinase) to invadopodia. It contains an N-terminal Phox homology (PX) domain and four SH3 domains. This model characterizes the second SH3 domain of Tks4. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 213009 [Multi-domain] Cd Length: 54 Bit Score: 47.72 E-value: 8.19e-07

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....
gi 1804876928  785 YKALYRFEARSHDEMSFNSGDIIQVDEKTIgePGWLYGSFQGNFGWFPCNYVEK 838
Cdd:cd12076      3 YTVIYPYTARDQDEINLEKGAVVEVIQKNL--EGWWKIRYQGKEGWAPASYLKK 54

Third (or C-terminal) Src Homology 3 domain of Sorbin and SH3 domain containing 1 (Sorbs1), also called ponsin; Sorbs1 is also called ponsin, SH3P12, or CAP (c-Cbl associated protein). It is an adaptor protein containing one sorbin homology (SoHo) and three SH3 domains. It binds Cbl and plays a major role in regulating the insulin signaling pathway by enhancing insulin-induced phosphorylation of Cbl. Sorbs1, like vinexin, localizes at cell-ECM and cell-cell adhesion sites where it binds vinculin, paxillin, and afadin. It may function in the control of cell motility. Other interaction partners of Sorbs1 include c-Abl, Sos, flotillin, Grb4, ataxin-7, filamin C, among others. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212849 [Multi-domain] Cd Length: 59 Bit Score: 47.68 E-value: 8.36e-07

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|..
gi 1804876928 1155 AMYDYVANNEDELNFSKGQLINVLNKDDPDWWQGEINGVT--GLFPSNYVKM 1204
Cdd:cd11916      6 ALYSYAPQNDDELELRDGDIVDVMEKCDDGWFVGTSRRTKqfGTFPGNYVKL 57

Family of unknown function (DUF5401); This is a family of unknown function found in Chromadorea.

Pssm-ID: 375164 [Multi-domain] Cd Length: 722 Bit Score: 53.97 E-value: 8.86e-07

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1804876928  384 QKIQEEEPQKKLPVTFEDKRKANYERGNVElEKRRQALMEQQQREAERKAQKEKEEWERKQRELQEQEWKKQleleKRLE 463
Cdd:pfam17380  404 VKILEEERQRKIQQQKVEMEQIRAEQEEAR-QREVRRLEEERAREMERVRLEEQERQQQVERLRQQEEERKR----KKLE 478

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1804876928  464 KQreleRQREEERRKEIERREAAKQELERQRRLEWERIRRQELLNQRNREQEEIVRLNSKKKslhlELEALNGKHQQISG 543
Cdd:pfam17380  479 LE----KEKRDRKRAEEQRRKILEKELEERKQAMIEEERKRKLLEKEMEERQKAIYEEERRR----EAEEERRKQQEMEE 550

                          170       180       190       200
                   ....*....|....*....|....*....|....*....|..
gi 1804876928  544 RLQ-DVRLRKQT-QKTEIEVLDKQCDL--EIMEIKQLQQELQ 581
Cdd:pfam17380  551 RRRiQEQMRKATeERSRLEAMEREREMmrQIVESEKARAEYE 592

Third Src Homology 3 domain of the fungal endocytic adaptor protein Sla1p; Sla1p facilitates endocytosis by playing a role as an adaptor protein in coupling components of the actin cytoskeleton to the endocytic machinery. It interacts with Abp1p, Las17p and Pan1p, which are activator proteins of actin-related protein 2/3 (Arp2/3). Sla1p contains multiple domains including three SH3 domains, a SAM (sterile alpha motif) domain, and a Sla1 homology domain 1 (SHD1), which binds to the NPFXD motif that is found in many integral membrane proteins such as the Golgi-localized Arf-binding protein Lsb5p and the P4-ATPases, Drs2p and Dnf1p. The third SH3 domain of Sla1p can bind ubiquitin while retaining the ability to bind proline-rich ligands; monoubiquitination of target proteins signals internalization and sorting through the endocytic pathway. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212709 [Multi-domain] Cd Length: 57 Bit Score: 47.31 E-value: 8.91e-07

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....*
gi 1804876928 1152 QVIAMYDYVANNEDELNFSKGQLINVLN-KDDPDWWQGEI--NGVTGLFPSNYVK 1203
Cdd:cd11775      2 RGKVLYDFDAQSDDELTVKEGDVVYILDdKKSKDWWMVENvsTGKEGVVPASYIE 56

Src homology 3 domain of Growth Arrest Specific protein 7; GAS7 is mainly expressed in the brain and is required for neurite outgrowth. It may also play a role in the protection and migration of embryonic stem cells. Treatment-related acute myeloid leukemia (AML) has been reported resulting from mixed-lineage leukemia (MLL)-GAS7 translocations as a complication of primary cancer treatment. GAS7 contains an N-terminal SH3 domain, followed by a WW domain, and a central F-BAR domain. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212763 [Multi-domain] Cd Length: 52 Bit Score: 47.51 E-value: 9.09e-07

                           10        20        30        40
                   ....*....|....*....|....*....|....*....|....*....
gi 1804876928 1155 AMYDYVANNEDE-LNFSKGQLINVLNKDDPDWWQGEINGVTGLFPSNYV 1202
Cdd:cd11829      4 TLYAFTGEQHQQgLSFEAGELIRVLQAPDGGWWEGEKDGLRGWFPASYV 52

Src homology 3 domain of Hematopoietic lineage cell-specific protein 1; HS1, also called HCLS1 (hematopoietic cell-specific Lyn substrate 1), is a cortactin homolog expressed specifically in hematopoietic cells. It is an actin regulatory protein that binds the Arp2/3 complex and stabilizes branched actin filaments. It is required for cell spreading and signaling in lymphocytes. It regulates cytoskeletal remodeling that controls lymphocyte trafficking, and it also affects tissue invasion and infiltration of leukemic B cells. Like cortactin, HS1 contains an N-terminal acidic domain, several copies of a repeat domain found in cortactin and HS1, a proline-rich region, and a C-terminal SH3 domain. The N-terminal region binds the Arp2/3 complex and F-actin, while the C-terminal region acts as an adaptor or scaffold that can connect varied proteins that bind the SH3 domain within the actin network. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 213006 [Multi-domain] Cd Length: 55 Bit Score: 47.52 E-value: 9.19e-07

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....*
gi 1804876928  787 ALYRFEARSHDEMSFNSGDII----QVDEktigepGWLYGSFQGNFGWFPCNYVE 837
Cdd:cd12073      5 ALYDYQGEGDDEISFDPQETItdieMVDE------GWWKGTCHGHRGLFPANYVE 53

Src homology 3 domain of Protein kinase C and Casein kinase Substrate in Neurons 1 (PACSIN1) and PACSIN 2; PACSIN 1 or Syndapin I (Synaptic dynamin-associated protein I) is expressed specifically in the brain and is localized in neurites and synaptic boutons. It binds the brain-specific proteins dynamin I, synaptojanin, synapsin I, and neural Wiskott-Aldrich syndrome protein (nWASP), and functions as a link between the cytoskeletal machinery and synaptic vesicle endocytosis. PACSIN 1 interacts with huntingtin and may be implicated in the neuropathology of Huntington's disease. PACSIN 2 or Syndapin II is expressed ubiquitously and is involved in the regulation of tubulin polymerization. It associates with Golgi membranes and forms a complex with dynamin II which is crucial in promoting vesicle formation from the trans-Golgi network. PACSINs act as regulators of cytoskeletal and membrane dynamics. Vetebrates harbor three isoforms with distinct expression patterns and specific functions. PACSINs contain an N-terminal F-BAR domain and a C-terminal SH3 domain. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212931 [Multi-domain] Cd Length: 56 Bit Score: 47.64 E-value: 9.22e-07

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....*..
gi 1804876928  783 VNYKALYRFEARSHDEMSFNSGD-IIQVDEKTigEPGWLYGSFQ-GNFGWFPCNYVE 837
Cdd:cd11998      1 VRVRALYDYDGQEQDELSFKAGDeLTKLEDED--EQGWCKGRLDsGQVGLYPANYVE 55

Src homology 3 domain of Phospholipase C (PLC) gamma; PLC catalyzes the hydrolysis of phosphatidylinositol (4,5)-bisphosphate [PtdIns(4,5)P2] to produce Ins(1,4,5)P3 and diacylglycerol (DAG) in response to various receptors. Ins(1,4,5)P3 initiates the calcium signaling cascade while DAG functions as an activator of PKC. PLCgamma catalyzes this reaction in tyrosine kinase-dependent signaling pathways. It is activated and recruited to its substrate at the membrane. Vertebrates contain two forms of PLCgamma, PLCgamma1, which is widely expressed, and PLCgamma2, which is primarily found in haematopoietic cells. PLCgamma contains a Pleckstrin homology (PH) domain followed by an elongation factor (EF) domain, two catalytic regions of PLC domains that flank two tandem SH2 domains, followed by a SH3 domain and C2 domain. The SH3 domain of PLCgamma1 directly interacts with dynamin-1 and can serve as a guanine nucleotide exchange factor (GEF). It also interacts with Cbl, inhibiting its phosphorylation and activity. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212759 [Multi-domain] Cd Length: 54 Bit Score: 47.33 E-value: 1.00e-06

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....
gi 1804876928  786 KALYRFEARSHDEMSFNSGDIIQVDEKTIGepGWLYGSFQG-NFGWFPCNYVEK 838
Cdd:cd11825      3 KALYDYRAQRPDELSFCKHAIITNVEKEDG--GWWRGDYGGkKQKWFPANYVEE 54

rad50; All proteins in this family for which functions are known are involvedin recombination, recombinational repair, and/or non-homologous end joining.They are components of an exonuclease complex with MRE11 homologs. This family is distantly related to the SbcC family of bacterial proteins.This family is based on the phylogenomic analysis of JA Eisen (1999, Ph.D. Thesis, Stanford University).

Pssm-ID: 129694 [Multi-domain] Cd Length: 1311 Bit Score: 53.90 E-value: 1.02e-06

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1804876928  384 QKIQEEEPQKKLPVTFEDKrkanyergnvELEKRRQALMEQQQREAERKAQKEKE----EWERKQRELQEQEwKKQLELE 459
Cdd:TIGR00606  200 QKVQEHQMELKYLKQYKEK----------ACEIRDQITSKEAQLESSREIVKSYEneldPLKNRLKEIEHNL-SKIMKLD 268

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1804876928  460 KRLEKQRELERQREEERRKEIERREAAKQELERQ------------RRLEWERIRRQELLNQRNREQEEivrLNSKKKSL 527
Cdd:TIGR00606  269 NEIKALKSRKKQMEKDNSELELKMEKVFQGTDEQlndlyhnhqrtvREKERELVDCQRELEKLNKERRL---LNQEKTEL 345

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1804876928  528 HLELEALNGK---HQQISGRLQDVRLRKQTQkTEIEVLDKQCDLEIM--------------EIKQLQQELQDYQNKLiyL 590
Cdd:TIGR00606  346 LVEQGRLQLQadrHQEHIRARDSLIQSLATR-LELDGFERGPFSERQiknfhtlvierqedEAKTAAQLCADLQSKE--R 422

                          250       260       270       280       290       300       310       320
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1804876928  591 VPEKQLLNERIKNMQLGNTPDLGIDLLHKKSLE----KEELCQRLKEQLDALEKETASKLSEMD----SFNNQLKCGNMD 662
Cdd:TIGR00606  423 LKQEQADEIRDEKKGLGRTIELKKEILEKKQEElkfvIKELQQLEGSSDRILELDQELRKAERElskaEKNSLTETLKKE 502

                          330       340       350       360       370       380       390       400
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1804876928  663 DSVLQCLLSLLSCLNNLfllLKELRESYNTQQLALEQLHKIKRDKLKEIERKR-------SELI-------QKKKLEDEA 728
Cdd:TIGR00606  503 VKSLQNEKADLDRKLRK---LDQEMEQLNHHTTTRTQMEMLTKDKMDKDEQIRkiksrhsDELTsllgyfpNKKQLEDWL 579

                          410       420       430       440       450
                   ....*....|....*....|....*....|....*....|....*....|
gi 1804876928  729 IRKAKQgkENLWRESLRKEEEEKQKRLQEE----KTQEKVQEEERKVEEK 774
Cdd:TIGR00606  580 HSKSKE--INQTRDRLAKLNKELASLEQNKnhinNELESKEEQLSSYEDK 627

Src Homology 3 domain of Sorting Nexin 9 and similar proteins; Sorting nexins (SNXs) are Phox homology (PX) domain containing proteins that are involved in regulating membrane traffic and protein sorting in the endosomal system. SNXs differ from each other in their lipid-binding specificity, subcellular localization and specific function in the endocytic pathway. This subfamily consists of SH3 domain containing SNXs including SNX9, SNX18, SNX33, and similar proteins. SNX9 is localized to plasma membrane endocytic sites and acts primarily in clathrin-mediated endocytosis, while SNX18 is localized to peripheral endosomal structures, and acts in a trafficking pathway that is clathrin-independent but relies on AP-1 and PACS1. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212697 [Multi-domain] Cd Length: 55 Bit Score: 47.32 E-value: 1.03e-06

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|...
gi 1804876928 1009 ALYSYSSVEPGDLTFIEGEEILVTQKDGE--WWTG--SIGDRtGIFPSNYVKP 1057
Cdd:cd11763      4 ALYDFDSQPSGELSLRAGEVLTITRQDVGdgWLEGrnSRGEV-GLFPSSYVEI 55

C-terminal (or second) Src homology 3 domain of VAV3 protein; VAV3 is ubiquitously expressed and functions as a phosphorylation-dependent guanine nucleotide exchange factor (GEF) for RhoA, RhoG, and Rac1. It has been implicated to function in the hematopoietic, bone, cerebellar, and cardiovascular systems. VAV3 is essential in axon guidance in neurons that control blood pressure and respiration. It is overexpressed in prostate cancer cells and it plays a role in regulating androgen receptor transcriptional activity. VAV proteins contain several domains that enable their function: N-terminal calponin homology (CH), acidic, RhoGEF (also called Dbl-homologous or DH), Pleckstrin Homology (PH), C1 (zinc finger), SH2, and two SH3 domains. The SH3 domain of VAV is involved in the localization of proteins to specific sites within the cell, by interacting with proline-rich sequences within target proteins. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212911 [Multi-domain] Cd Length: 56 Bit Score: 47.33 E-value: 1.03e-06

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|..
gi 1804876928  787 ALYRFEARSHDEMSFNSGDIIQVDEKTiGEPGWLYGSFQGNFGWFPCNYVEK 838
Cdd:cd11978      5 ARYDFCARDMRELSLLKGDVVKIYTKM-STNGWWRGEVNGRVGWFPSTYVEE 55

First Src Homology 3 domain of Bzz1 and similar domains; Bzz1 (or Bzz1p) is a WASP/Las17-interacting protein involved in endocytosis and trafficking to the vacuole. It physically interacts with type I myosins and functions in the early steps of endocytosis. Together with other proteins, it induces membrane scission in yeast. Bzz1 contains an N-terminal F-BAR (FES-CIP4 Homology and Bin/Amphiphysin/Rvs), a central coiled-coil, and two C-terminal SH3 domains. This model represents the first C-terminal SH3 domain. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212845 [Multi-domain] Cd Length: 55 Bit Score: 47.22 E-value: 1.06e-06

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|...
gi 1804876928 1155 AMYDYVANNEDELNFSKGQLINVLNKDDPDWWQgEI---NGVTGLFPSNYVKM 1204
Cdd:cd11912      4 VLYDYTASGDDEVSISEGEEVTVLEPDDGSGWT-KVrngSGEEGLVPTSYIEI 55

Src Homology 3 domain of Apoptosis Stimulating of p53 protein 1; ASPP1, like ASPP2, activates the apoptotic function of the p53 family of tumor suppressors (p53, p63, and p73). In addition, it functions in the cytoplasm to regulate the nuclear localization of the transcriptional cofactors YAP and TAZ by inihibiting their phosphorylation; YAP and TAZ are important regulators of cell expansion, differentiation, migration, and invasion. ASPP1 is downregulated in breast tumors expressing wild-type p53. It contains a proline-rich region, four ankyrin (ANK) repeats, and an SH3 domain at its C-terminal half. The SH3 domain and the ANK repeats of ASPP1 contribute to the p53 binding site; they bind to the DNA binding domain of p53. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212887 [Multi-domain] Cd Length: 57 Bit Score: 47.32 E-value: 1.06e-06

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|.
gi 1804876928 1153 VIAMYDYVANNEDELNFSKGQLINVLNKDD---PDWWQGEINGVTGLFPSN 1200
Cdd:cd11954      3 VYALWDYEAQNADELSFQEGDAITILRRKDdseTEWWWARLNDKEGYVPKN 53

exonuclease SbcC; All proteins in this family for which functions are known are part of an exonuclease complex with sbcD homologs. This complex is involved in the initiation of recombination to regulate the levels of palindromic sequences in DNA. This family is based on the phylogenomic analysis of JA Eisen (1999, Ph.D. Thesis, Stanford University). [DNA metabolism, DNA replication, recombination, and repair]

Pssm-ID: 129705 [Multi-domain] Cd Length: 1042 Bit Score: 53.82 E-value: 1.08e-06

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1804876928  384 QKIQEEEPQKKLPVTFEDKRKANYERGNVELEKRRQALMEQQQR-----EAERKAQKEKEEwERKQRELQEQEWKKQLEL 458
Cdd:TIGR00618  249 REAQEEQLKKQQLLKQLRARIEELRAQEAVLEETQERINRARKAaplaaHIKAVTQIEQQA-QRIHTELQSKMRSRAKLL 327

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1804876928  459 EKR--LEKQRELERQREEERRKEIERREAAKQELERQRRLEWERIRRQELLNQRNREQEEIVRLNSKKKSLHLELEALNG 536
Cdd:TIGR00618  328 MKRaaHVKQQSSIEEQRRLLQTLHSQEIHIRDAHEVATSIREISCQQHTLTQHIHTLQQQKTTLTQKLQSLCKELDILQR 407

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1804876928  537 KHQQISGRLQDVRLRKQtqktEIEVLDKQCDLEIMEIKQLQQ----ELQDYQNKLIYLVPEKQLLNERIKnmQLGNtpdl 612
Cdd:TIGR00618  408 EQATIDTRTSAFRDLQG----QLAHAKKQQELQQRYAELCAAaitcTAQCEKLEKIHLQESAQSLKEREQ--QLQT---- 477

                          250       260       270       280       290       300       310       320
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1804876928  613 gIDLLHKKSLEKEELCQRLKEQLDALEKETASKLSEMDSFNNQLKCGNMDDSVLQCLLSLLSClnnlflLLKELRESYNT 692
Cdd:TIGR00618  478 -KEQIHLQETRKKAVVLARLLELQEEPCPLCGSCIHPNPARQDIDNPGPLTRRMQRGEQTYAQ------LETSEEDVYHQ 550

                          330       340       350       360       370       380       390       400
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1804876928  693 QQLALEQLhKIKRDKLKEIERKRSELIQKKKLEDEAIRKAKQGKENLWRESLRKEEEEKQKRL----QEEKTQEKVQEEE 768
Cdd:TIGR00618  551 LTSERKQR-ASLKEQMQEIQQSFSILTQCDNRSKEDIPNLQNITVRLQDLTEKLSEAEDMLACeqhaLLRKLQPEQDLQD 629

                          410
                   ....*....|....
gi 1804876928  769 RKVEEKQCEPASAL 782
Cdd:TIGR00618  630 VRLHLQQCSQELAL 643

Synaptonemal complex protein 1 (SCP-1); Synaptonemal complex protein 1 (SCP-1) is the major component of the transverse filaments of the synaptonemal complex. Synaptonemal complexes are structures that are formed between homologous chromosomes during meiotic prophase.

Pssm-ID: 114219 [Multi-domain] Cd Length: 787 Bit Score: 53.57 E-value: 1.08e-06

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1804876928  384 QKIQEEEPQKKLPVTFEDKR-KANyergnvELEKRRQALMEQQQREAERKAQKEKEEWERK---QRELQEQE-------- 451
Cdd:pfam05483  248 QITEKENKMKDLTFLLEESRdKAN------QLEEKTKLQDENLKELIEKKDHLTKELEDIKmslQRSMSTQKaleedlqi 321

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1804876928  452 -WKKQLELEKRLEKQRELERQREEERRKEIERREAAKQELERQRRLEWERIrrqellnQRNREQEEIVRLNSKKKSLHLE 530
Cdd:pfam05483  322 aTKTICQLTEEKEAQMEELNKAKAAHSFVVTEFEATTCSLEELLRTEQQRL-------EKNEDQLKIITMELQKKSSELE 394

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1804876928  531 --LEALNGKHQQISgRLQDVRLRKQTqkteieVLDkqcdlEIMEIKQLQQELQDYQNKLIYLvpekqlLNERIKNMQlgn 608
Cdd:pfam05483  395 emTKFKNNKEVELE-ELKKILAEDEK------LLD-----EKKQFEKIAEELKGKEQELIFL------LQAREKEIH--- 453

                          250       260       270       280       290       300       310       320
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1804876928  609 tpDLGIDLLHKKSLEkEELCQRLKEQLDALEKETAsKLSEMDSFNNQLKCGNmddsvlqclLSLLSCLNNLFLLLKELRE 688
Cdd:pfam05483  454 --DLEIQLTAIKTSE-EHYLKEVEDLKTELEKEKL-KNIELTAHCDKLLLEN---------KELTQEASDMTLELKKHQE 520

                          330       340       350       360       370       380       390       400
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1804876928  689 SYNT----QQLALEQLHKIKRDKLK---EIERKRSELIQK---------------KKLEDEAIRKAKQGKENLWR-ESLR 745
Cdd:pfam05483  521 DIINckkqEERMLKQIENLEEKEMNlrdELESVREEFIQKgdevkckldkseenaRSIEYEVLKKEKQMKILENKcNNLK 600

                          410       420       430
                   ....*....|....*....|....*....|....*....
gi 1804876928  746 KEEEEKQKRLQEEKTQEKVQEEERKVEEKQCEPASALVN 784
Cdd:pfam05483  601 KQIENKNKNIEELHQENKALKKKGSAENKQLNAYEIKVN 639

Src homology 3 domain of SH3 domain containing Ysc84-like 1 (SH3YL1) protein; SH3YL1 localizes to the plasma membrane and is required for dorsal ruffle formation. It binds phosphoinositides (PIs) with high affinity through its N-terminal SYLF domain (also called DUF500). In addition, SH3YL1 contains a C-terminal SH3 domain which has been reported to bind to N-WASP, dynamin 2, and SHIP2 (a PI 5-phosphatase). SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212775 Cd Length: 54 Bit Score: 47.00 E-value: 1.19e-06

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|...
gi 1804876928  924 AQALCSWTAKKDNHLNFSKHDIITVL---EQQENWWFGEVHGGRGWFPKSYVK 973
Cdd:cd11841      2 VTALYSFEGQQPCDLSFQAGDRITVLtrtDSQFDWWEGRLRGRVGIFPANYVS 54

Second Src Homology 3 domain (SH3B) of CD2-associated protein and similar proteins; This subfamily is composed of the second SH3 domain (SH3B) of CD2AP, CIN85 (Cbl-interacting protein of 85 kDa), and similar domains. CD2AP and CIN85 are adaptor proteins that bind to protein partners and assemble complexes that have been implicated in T cell activation, kidney function, and apoptosis of neuronal cells. They also associate with endocytic proteins, actin cytoskeleton components, and other adaptor proteins involved in receptor tyrosine kinase (RTK) signaling. CD2AP and the main isoform of CIN85 contain three SH3 domains, a proline-rich region, and a C-terminal coiled-coil domain. All of these domains enable CD2AP and CIN85 to bind various protein partners and assemble complexes that have been implicated in many different functions. SH3B of both proteins have been shown to bind to Cbl. In the case of CD2AP, its SH3B binds to Cbl at a site distinct from the c-Cbl/SH3A binding site. The CIN85 SH3B also binds ubiquitin. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212807 [Multi-domain] Cd Length: 53 Bit Score: 46.94 E-value: 1.22e-06

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|
gi 1804876928 1009 ALYSYSSVEPGDLTFIEGE--EILVTQKDGeWWTGSIGDRTGIFPSNYVK 1056
Cdd:cd11874      4 VLFSYTPQNEDELELKVGDtiEVLGEVEEG-WWEGKLNGKVGVFPSNFVK 52

Src homology 3 domain of Myosins Ie, If, and similar proteins; Myosins Ie (MyoIe) and If (MyoIf) are nonmuscle, unconventional, long tailed, class I myosins containing an N-terminal motor domain and a myosin tail with TH1, TH2, and SH3 domains. MyoIe interacts with the endocytic proteins, dynamin and synaptojanin-1, through its SH3 domain; it may play a role in clathrin-dependent endocytosis. In the kidney, MyoIe is critical for podocyte function and normal glomerular filtration. Mutations in MyoIe is associated with focal segmental glomerulosclerosis, a disease characterized by massive proteinuria and progression to end-stage kidney disease. MyoIf is predominantly expressed in the immune system; it plays a role in immune cell motility and innate immunity. Mutations in MyoIf may be associated with the loss of hearing. The MyoIf gene has also been found to be fused to the MLL (Mixed lineage leukemia) gene in infant acute myeloid leukemias (AML). SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212761 [Multi-domain] Cd Length: 53 Bit Score: 47.02 E-value: 1.23e-06

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|
gi 1804876928 1084 AYVASGSEQLSLAPGQLILILKKNSSGWWQGELqaRGKkrqKGWFPASHV 1133
Cdd:cd11827      7 AYDAQDTDELSFNEGDIIEILKEDPSGWWTGRL--RGK---EGLFPGNYV 51

Src Homology 3 domain of Cytokinesis protein 3 and similar proteins; Cytokinesis protein 3 (Cyk3 or Cyk3p) is a component of the actomyosin ring independent cytokinesis pathway in yeast. It interacts with Inn1 and facilitates its recruitment to the bud neck, thereby promoting cytokinesis. Cyk3p contains an N-terminal SH3 domain and a C-terminal transglutaminase-like domain. The Cyk3p SH3 domain binds to the C-terminal proline-rich region of Inn1. SH3 domains bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs; they play a role in the regulation of enzymes by intramolecular interactions, changing the subcellular localization of signal pathway components and mediate multiprotein complex assemblies.

Pssm-ID: 212822 Cd Length: 53 Bit Score: 47.11 E-value: 1.23e-06

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|..
gi 1804876928 1153 VIAMYDYVANNEDELNFSKGQLINVLNKDDPDWWQGEI--NGVTGLFPSNYV 1202
Cdd:cd11889      2 VKAVYSWAGETEGDLGFLEGDLIEVLSIGDGSWWSGKLrrNGAEGIFPSNFV 53

C-terminal Src Homology 3 domain of Nebulin; Nebulin is a giant filamentous protein (600-900 kD) that is expressed abundantly in skeletal muscle. It binds to actin thin filaments and regulates its assembly and function. Nebulin was thought to be part of a molecular ruler complex that is critical in determining the lengths of actin thin filaments in skeletal muscle since its length, which varies due to alternative splicing, correlates with the length of thin filaments in various muscle types. Recent studies indicate that nebulin regulates thin filament length by stabilizing the filaments and preventing depolymerization. Mutations in nebulin can cause nemaline myopathy, characterized by muscle weakness which can be severe and can lead to neonatal lethality. Nebulin contains an N-terminal LIM domain, many nebulin repeats/super repeats, and a C-terminal SH3 domain. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212866 [Multi-domain] Cd Length: 58 Bit Score: 46.92 E-value: 1.33e-06

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|.
gi 1804876928 1155 AMYDYVANNEDELNFSKGQLINVLNKDDPDWWQGEIN--GVTGLFPSNYVK 1203
Cdd:cd11933      6 AMYDYRAADDDEVSFKDGDTIVNVQTIDEGWMYGTVQrtGKTGMLPANYVE 56

Src homology 3 domain of ARHGEF9-like Rho guanine nucleotide exchange factors; Members of this family contain a SH3 domain followed by RhoGEF (also called Dbl-homologous or DH) and Pleckstrin Homology (PH) domains. They include the Rho guanine nucleotide exchange factors ARHGEF9, ASEF (also called ARHGEF4), ASEF2, and similar proteins. GEFs activate small GTPases by exchanging bound GDP for free GTP. ARHGEF9 specifically activates Cdc42, while both ASEF and ASEF2 can activate Rac1 and Cdc42. ARHGEF9 is highly expressed in the brain and it interacts with gephyrin, a postsynaptic protein associated with GABA and glycine receptors. ASEF plays a role in angiogenesis and cell migration. ASEF2 is important in cell migration and adhesion dynamics. ASEF exists in an autoinhibited form and is activated upon binding of the tumor suppressor APC (adenomatous polyposis coli), leading to the activation of Rac1 or Cdc42. In its autoinhibited form, the SH3 domain of ASEF forms an extensive interface with the DH and PH domains, blocking the Rac binding site. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212762 [Multi-domain] Cd Length: 53 Bit Score: 46.99 E-value: 1.33e-06

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|...
gi 1804876928  923 KAQALCSWTAKKDNHLNFSKHDIITVLEQQE-NWWFGEVHGGRGWFPKSYVKI 974
Cdd:cd11828      1 LAEALWDHVTMDPEELGFKAGDVIEVLDMSDkDWWWGSIRDEEGWFPASFVRL 53

Src homology 3 domains of Rab3-interacting molecules (RIMs) binding proteins; RIMs binding proteins (RBPs, RIM-BPs) associate with calcium channels present in photoreceptors, neurons, and hair cells; they interact simultaneously with specific calcium channel subunits, and active zone proteins, RIM1 and RIM2. RIMs are part of the matrix at the presynaptic active zone and are associated with synaptic vesicles through their interaction with the small GTPase Rab3. RIM-BPs play a role in regulating synaptic transmission by serving as adaptors and linking calcium channels with the synaptic vesicle release machinery. RIM-BPs contain three SH3 domains and two to three fibronectin III repeats. Invertebrates contain one, while vertebrates contain at least two RIM-BPs, RIM-BP1 and RIM-BP2. RIM-BP1 is also called peripheral-type benzodiazapine receptor associated protein 1 (PRAX-1). Mammals contain a third protein, RIM-BP3. RIM-BP1 and RIM-BP2 are predominantly expressed in the brain where they display overlapping but distinct expression patterns, while RIM-BP3 is almost exclusively expressed in the testis and is essential in spermiogenesis. The SH3 domains of RIM-BPs bind to the PxxP motifs of RIM1, RIM2, and L-type (alpha1D) and N-type (alpha1B) calcium channel subunits. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212785 Cd Length: 62 Bit Score: 46.93 E-value: 1.38e-06

                           10        20        30        40        50        60
                   ....*....|....*....|....*....|....*....|....*....|....*....|
gi 1804876928 1153 VIAMYDY-------VANNEDELNFSKGQLINVL-NKDDPDWWQGEINGV-TGLFPSNYVK 1203
Cdd:cd11851      2 MVALYDYnpetmspNDDPEEELSFHAGDVVRVYgPMDEDGFYYGELEGGrKGLVPSNFVQ 61

Second Src homology 3 domain of Tyrosine kinase substrate with four SH3 domains; Tks4, also called SH3 and PX domain-containing protein 2B (SH3PXD2B) or HOFI, is a Src substrate and scaffolding protein that plays an important role in the formation of podosomes and invadopodia, the dynamic actin-rich structures that are related to cell migration and cancer cell invasion. It is required in the formation of functional podosomes, EGF-induced membrane ruffling, and lamellipodia generation. It plays an important role in cellular attachment and cell spreading. Tks4 is essential for the localization of MT1-MMP (membrane-type 1 matrix metalloproteinase) to invadopodia. It contains an N-terminal Phox homology (PX) domain and four SH3 domains. This model characterizes the second SH3 domain of Tks4. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 213009 [Multi-domain] Cd Length: 54 Bit Score: 46.95 E-value: 1.40e-06

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|
gi 1804876928 1154 IAMYDYVANNEDELNFSKGQLINVLNKDDPDWWQGEINGVTGLFPSNYVK 1203
Cdd:cd12076      4 TVIYPYTARDQDEINLEKGAVVEVIQKNLEGWWKIRYQGKEGWAPASYLK 53

chromosome segregation protein SMC, primarily archaeal type; SMC (structural maintenance of chromosomes) proteins bind DNA and act in organizing and segregating chromosomes for partition. SMC proteins are found in bacteria, archaea, and eukaryotes. It is found in a single copy and is homodimeric in prokaryotes, but six paralogs (excluded from this family) are found in eukarotes, where SMC proteins are heterodimeric. This family represents the SMC protein of archaea and a few bacteria (Aquifex, Synechocystis, etc); the SMC of other bacteria is described by TIGR02168. The N- and C-terminal domains of this protein are well conserved, but the central hinge region is skewed in composition and highly divergent. [Cellular processes, Cell division, DNA metabolism, Chromosome-associated proteins]

Pssm-ID: 274009 [Multi-domain] Cd Length: 1164 Bit Score: 53.53 E-value: 1.44e-06

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1804876928  486 AKQELERQRRLeweRIRRQELLNQRNREQEEIVRLNSKKKSLHLELEALNGKHQQISGRLQDVRLRKQTQKTEIEVLDKQ 565
Cdd:TIGR02169  669 SRSEPAELQRL---RERLEGLKRELSSLQSELRRIENRLDELSQELSDASRKIGEIEKEIEQLEQEEEKLKERLEELEED 745

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1804876928  566 cdleimeIKQLQQELQDYQNKLIYLVPEKQLLNERIKNMQLgNTPDLGIDLLHKKSLEKEELCQRLKEQLDALEKetask 645
Cdd:TIGR02169  746 -------LSSLEQEIENVKSELKELEARIEELEEDLHKLEE-ALNDLEARLSHSRIPEIQAELSKLEEEVSRIEA----- 812

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1804876928  646 lsemdsfnnqlkcgnmddsvlqcllsllsclnnlflLLKELRESYNTQQLALEQLhkikRDKLKEIERKRSELIQKKKLe 725
Cdd:TIGR02169  813 ------------------------------------RLREIEQKLNRLTLEKEYL----EKEIQELQEQRIDLKEQIKS- 851

                          250       260       270       280       290       300
                   ....*....|....*....|....*....|....*....|....*....|....*....|
gi 1804876928  726 deaiRKAKQGKENLWRESLRKEEEEKQKRLQE--------EKTQEKVQEEERKVEEKQCE 777
Cdd:TIGR02169  852 ----IEKEIENLNGKKEELEEELEELEAALRDlesrlgdlKKERDELEAQLRELERKIEE 907

Src Homology 3 domain of beta-Pak Interactive eXchange factor; Beta-PIX, also called Rho guanine nucleotide exchange factor 7 (ARHGEF7) or Cool (Cloned out of Library)-1, activates small GTPases by exchanging bound GDP for free GTP. It acts as a GEF for both Cdc42 and Rac 1, and plays important roles in regulating neuroendocrine exocytosis, focal adhesion maturation, cell migration, synaptic vesicle localization, and insulin secretion. PIX proteins contain an N-terminal SH3 domain followed by RhoGEF (also called Dbl-homologous or DH) and Pleckstrin Homology (PH) domains, and a C-terminal leucine-zipper domain for dimerization. The SH3 domain of PIX binds to an atypical PxxxPR motif in p21-activated kinases (PAKs) with high affinity. The binding of PAKs to PIX facilitate the localization of PAKs to focal complexes and also localizes PAKs to PIX targets Cdc43 and Rac, leading to the activation of PAKs. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212994 [Multi-domain] Cd Length: 54 Bit Score: 46.99 E-value: 1.48e-06

                           10        20        30        40
                   ....*....|....*....|....*....|....*....|
gi 1804876928  935 DNHLNFSKHDIITVLEQQEN-WWFGEVHGGRGWFPKSYVK 973
Cdd:cd12061     13 EDELSFSKGDVIHVTRVEEGgWWEGTHNGRTGWFPSNYVR 52

Src homology 3 domain of ArfGAP with SH3 domain, ankyrin repeat and PH domain containing protein 2; ASAP2 is also called DDEF2 (Development and Differentiation Enhancing Factor 2), AMAP2, centaurin beta-3, or PAG3. It mediates the functions of Arf GTPases vial dual mechanisms: it exhibits GTPase activating protein (GAP) activity towards class I (Arf1) and II (Arf5) Arfs; and it binds class III Arfs (GTP-Arf6) stably without GAP activity. It binds paxillin and is implicated in Fcgamma receptor-mediated phagocytosis in macrophages and in cell migration. ASAP2 contains an N-terminal BAR domain, followed by a Pleckstrin homology (PH) domain, an Arf GAP domain, ankyrin (ANK) repeats, and a C-terminal SH3 domain. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212899 Cd Length: 56 Bit Score: 46.87 E-value: 1.56e-06

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|.
gi 1804876928 1009 ALYSYSSVEPGDLTFIEGEEILVT-QKDGEWWTGSI-GD--RTGIFPSNYV 1055
Cdd:cd11966      4 ALYNCVADNPDELTFSEGEIIIVDgEEDKEWWIGHIdGEptRRGAFPVSFV 54

Src homology 3 domain of Brk (Breast tumor kinase) Protein Tyrosine Kinase (PTK), also called PTK6; Brk is a cytoplasmic (or non-receptor) PTK with limited homology to Src kinases. It has been found to be overexpressed in a majority of breast tumors. It plays roles in normal cell differentiation, proliferation, survival, migration, and cell cycle progression. Brk substrates include RNA-binding proteins (SLM-1/2, Sam68), transcription factors (STAT3/5), and signaling molecules (Akt, paxillin, IRS-4). Src kinases in general contain an N-terminal SH4 domain with a myristoylation site, followed by SH3 and SH2 domains, a tyr kinase domain, and a regulatory C-terminal region containing a conserved tyr; they are activated by autophosphorylation at the tyr kinase domain, but are negatively regulated by phosphorylation at the C-terminal tyr by Csk (C-terminal Src Kinase). However, Brk lacks the N-terminal myristoylation site. The SH3 domain of Src kinases contributes to substrate recruitment by binding adaptor proteins/substrates, and regulation of kinase activity through an intramolecular interaction. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212781 [Multi-domain] Cd Length: 58 Bit Score: 46.78 E-value: 1.73e-06

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....*
gi 1804876928 1007 YIALYSYSSVEPGDLTFIEGEEILVTQKDGEWWTGSIGDR------TGIFPSNYV 1055
Cdd:cd11847      2 YKALWDFKARGDEELSFQAGDQFRIAERSGDWWTALKLDRaggvvaQGFVPNNYL 56

Src Homology 3 domain of SH3 domain-containing protein 21 (SH3D21) and similar proteins; N-terminal SH3 domain of the uncharacterized protein SH3 domain-containing protein 21, and similar uncharacterized domains, it belongs to the CD2AP-like_3 subfamily of proteins. The CD2AP-like_3 subfamily is composed of the third SH3 domain (SH3C) of CD2AP, CIN85 (Cbl-interacting protein of 85 kDa), and similar domains. CD2AP and CIN85 are adaptor proteins that bind to protein partners and assemble complexes that have been implicated in T cell activation, kidney function, and apoptosis of neuronal cells. They also associate with endocytic proteins, actin cytoskeleton components, and other adaptor proteins involved in receptor tyrosine kinase (RTK) signaling. CD2AP and the main isoform of CIN85 contain three SH3 domains, a proline-rich region, and a C-terminal coiled-coil domain. All of these domains enable CD2AP and CIN85 to bind various protein partners and assemble complexes that have been implicated in many different functions. SH3C of both proteins have been shown to bind to ubiquitin. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 213018 [Multi-domain] Cd Length: 55 Bit Score: 46.69 E-value: 1.78e-06

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|...
gi 1804876928  923 KAQALCSWTAKKDNHLNFSKHDIITVLEQQ---ENWWFGEVHGGRGWFPKSYV 972
Cdd:cd12142      1 YCRVLFDYNPVAPDELALKKGDVIEVISKEtedEGWWEGELNGRRGFFPDNFV 53

C-terminal Src homology 3 domain of Growth factor receptor-bound protein 2; GRB2 is a critical signaling molecule that regulates the Ras pathway by linking tyrosine kinases to the Ras guanine nucleotide releasing protein Sos (son of sevenless), which converts Ras to the active GTP-bound state. It is ubiquitously expressed in all tissues throughout development and is important in cell cycle progression, motility, morphogenesis, and angiogenesis. In lymphocytes, GRB2 is associated with antigen receptor signaling components. GRB2 contains an N-terminal SH3 domain, a central SH2 domain, and a C-terminal SH3 domain. The C-terminal SH3 domain of GRB2 binds to Gab2 (Grb2-associated binder 2) through epitopes containing RxxK motifs, as well as to the proline-rich C-terminus of FGRF2. SH3 domains are protein interaction domains that typically bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212882 [Multi-domain] Cd Length: 53 Bit Score: 46.37 E-value: 1.78e-06

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|..
gi 1804876928  786 KALYRFEARSHDEMSFNSGDIIQVDEKTigEPGWLYGSFQGNFGWFPCNYVE 837
Cdd:cd11949      3 QALFDFDPQEDGELGFRRGDFIEVMDNS--DPNWWKGACHGQTGMFPRNYVT 52

Src homology 3 domain of ARHGEF9-like Rho guanine nucleotide exchange factors; Members of this family contain a SH3 domain followed by RhoGEF (also called Dbl-homologous or DH) and Pleckstrin Homology (PH) domains. They include the Rho guanine nucleotide exchange factors ARHGEF9, ASEF (also called ARHGEF4), ASEF2, and similar proteins. GEFs activate small GTPases by exchanging bound GDP for free GTP. ARHGEF9 specifically activates Cdc42, while both ASEF and ASEF2 can activate Rac1 and Cdc42. ARHGEF9 is highly expressed in the brain and it interacts with gephyrin, a postsynaptic protein associated with GABA and glycine receptors. ASEF plays a role in angiogenesis and cell migration. ASEF2 is important in cell migration and adhesion dynamics. ASEF exists in an autoinhibited form and is activated upon binding of the tumor suppressor APC (adenomatous polyposis coli), leading to the activation of Rac1 or Cdc42. In its autoinhibited form, the SH3 domain of ASEF forms an extensive interface with the DH and PH domains, blocking the Rac binding site. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212762 [Multi-domain] Cd Length: 53 Bit Score: 46.61 E-value: 1.79e-06

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|.
gi 1804876928 1085 YVASGSEQLSLAPGQLILILKKNSSGWWQGELQARgkkrqKGWFPASHVKL 1135
Cdd:cd11828      8 HVTMDPEELGFKAGDVIEVLDMSDKDWWWGSIRDE-----EGWFPASFVRL 53

First Src Homology 3 domain of SH3 domain containing ring finger 3, an E3 ubiquitin-protein ligase; SH3RF3 is also called POSH2 (Plenty of SH3s 2) or SH3MD4 (SH3 multiple domains protein 4). It is a scaffold protein with E3 ubiquitin-protein ligase activity. It was identified in the screen for interacting partners of p21-activated kinase 2 (PAK2). It may play a role in regulating JNK mediated apoptosis in certain conditions. It also interacts with GTP-loaded Rac1. SH3RF3 is highly homologous to SH3RF1; it also contains an N-terminal RING finger domain and four SH3 domains. This model represents the first SH3 domain, located at the N-terminal half, of SH3RF3. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212861 Cd Length: 54 Bit Score: 46.45 E-value: 1.79e-06

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|..
gi 1804876928  786 KALYRFEARSHDEMSFNSGDIIQVDEKTigEPGWLYGSFQGNFGWFPCNYVE 837
Cdd:cd11928      4 KALYSYEGKEPGDLKFNKGDIIILRRKV--DENWYHGELNGCHGFLPASYIQ 53

Src homology 3 domain of Abl Interactor proteins; Abl interactor (Abi) proteins are adaptor proteins serving as binding partners and substrates of Abl tyrosine kinases. They are involved in regulating actin cytoskeletal reorganization and play important roles in membrane-ruffling, endocytosis, cell motility, and cell migration. They localize to sites of actin polymerization in epithelial adherens junction and immune synapses, as well as to the leading edge of lamellipodia. Vertebrates contain two Abi proteins, Abi1 and Abi2. Abi1 displays a wide expression pattern while Abi2 is highly expressed in the eye and brain. Abi proteins contain a homeobox homology domain, a proline-rich region, and a SH3 domain. The SH3 domain of Abi binds to a PxxP motif in Abl. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212760 [Multi-domain] Cd Length: 52 Bit Score: 46.55 E-value: 1.82e-06

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|.
gi 1804876928  923 KAQALCSWTAKKDNHLNFSKHDIITVLEQQEN-WWFGEVHGGRGWFPKSYV 972
Cdd:cd11826      1 KVVALYDYTADKDDELSFQEGDIIYVTKKNDDgWYEGVLNGVTGLFPGNYV 51

Src Homology 3 domain of Src Kinase-Associated Phosphoprotein 1; SKAP1, also called SKAP55 (Src kinase-associated protein of 55kDa), is an immune cell-specific adaptor protein that plays an important role in T-cell adhesion, migration, and integrin clustering. It is expressed exclusively in T-lymphocytes, mast cells, and macrophages. Binding partners include ADAP (adhesion and degranulation-promoting adaptor protein), Fyn, Riam, RapL, and RasGRP. It contains a pleckstrin homology (PH) domain, a C-terminal SH3 domain, and several tyrosine phosphorylation sites. The SH3 domain of SKAP1 is necessary for its ability to regulate T-cell conjugation with antigen-presenting cells and the formation of LFA-1 clusters. SKAP1 binds primarily to a proline-rich region of ADAP through its SH3 domain; its degradation is regulated by ADAP. A secondary interaction occurs via the ADAP SH3 domain and the RKxxYxxY motif in SKAP1. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212977 Cd Length: 53 Bit Score: 46.39 E-value: 1.84e-06

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|
gi 1804876928 1155 AMYDYVANNEDELNFSKGQLINVLNKDDP--DWWQGEINGVTGLFPSNYV 1202
Cdd:cd12044      4 GLWDCFGDNPDELSFQRGDLIYILSKEYNmyGWWVGELNGIVGIVPKDYL 53

Src homology 3 domain of Phospholipase C (PLC) gamma 2; PLCgamma2 is primarily expressed in haematopoietic cells, specifically in B cells. It is activated by tyrosine phosphorylation by B cell receptor (BCR) kinases and is recruited to the plasma membrane where its substrate is located. It is required in pre-BCR signaling and in the maturation of B cells. PLCs catalyze the hydrolysis of phosphatidylinositol (4,5)-bisphosphate [PtdIns(4,5)P2] to produce Ins(1,4,5)P3 and diacylglycerol (DAG). Ins(1,4,5)P3 initiates the calcium signaling cascade while DAG functions as an activator of PKC. PLCgamma contains a Pleckstrin homology (PH) domain followed by an elongation factor (EF) domain, two catalytic regions of PLC domains that flank two tandem SH2 domains, followed by a SH3 domain and C2 domain. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212902 Cd Length: 55 Bit Score: 46.37 E-value: 1.87e-06

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|
gi 1804876928 1009 ALYSYSSVEPGDLTFIEGEEIL-VTQKDGEWWTGSIGDRTG-IFPSNYVK 1056
Cdd:cd11969      4 ALYDYRAKRSDELSFCKGALIHnVSKETGGWWKGDYGGKVQhYFPSNYVE 53

Fifth Src homology 3 domain (or SH3E) of Intersectin-2; Intersectin-2 (ITSN2) is an adaptor protein that functions in exo- and endocytosis, actin cytoskeletal reorganization, and signal transduction. It plays a role in clathrin-coated pit (CCP) formation. It binds to many proteins through its multidomain structure and facilitate the assembly of multimeric complexes. ITSN2 also functions as a specific GEF for Cdc42 activation in epithelial morphogenesis, and is required in mitotic spindle orientation. It exists in alternatively spliced short and long isoforms. The short isoform contains two Eps15 homology domains (EH1 and EH2), a coiled-coil region and five SH3 domains (SH3A-E), while the long isoform, in addition, contains RhoGEF (also called Dbl-homologous or DH), Pleckstrin homology (PH) and C2 domains. The fifth SH3 domain (or SH3E) of ITSN2 is expected to bind protein partners, similar to ITSN1 which has been shown to bind many protein partners including SGIP1, Sos1, dynamin1/2, CIN85, c-Cbl, SHIP2, N-WASP, and synaptojanin-1, among others. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212929 [Multi-domain] Cd Length: 54 Bit Score: 46.51 E-value: 1.90e-06

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|.
gi 1804876928 1085 YVASGSEQLSLAPGQLILILKKNSSGWWQGELQArgkkrQKGWFPASHVKL 1135
Cdd:cd11996      9 YTANNEDELSFSKGQLINVLNKDDPDWWQGEING-----VTGLFPSNYVKM 54

C-terminal Src homology 3 domain of SH3 and cysteine-rich domain-containing protein 2 (Stac2); Stac proteins are putative adaptor proteins that contain a cysteine-rich C1 domain and one or two SH3 domains at the C-terminus. There are three mammalian members (Stac1, Stac2, and Stac3) of this family. Stac2 contains a single SH3 domain at the C-terminus unlike Stac1 and Stac3, which contain two C-terminal SH3 domains. Stac1 and Stac2 have been found to be expressed differently in mature dorsal root ganglia (DRG) neurons. Stac1 is mainly expressed in peptidergic neurons while Stac2 is found in a subset of nonpeptidergic and all trkB+ neurons. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212918 Cd Length: 53 Bit Score: 46.48 E-value: 1.91e-06

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|
gi 1804876928 1154 IAMYDYVANNEDELNFSKGQLINVLNKDDPDWWQGEINGVTGLFPSNYVK 1203
Cdd:cd11985      3 VALYKFLPQENNDLPLQPGDRVMVVDDSNEDWWKGKSGDRVGFFPANFVQ 52

Src Homology 3 domain of SH3 domain-binding protein 4; SH3 domain-binding protein 4 (SH3BP4) is also called transferrin receptor trafficking protein (TTP). SH3BP4 is an endocytic accessory protein that interacts with endocytic proteins including clathrin and dynamin, and regulates the internalization of the transferrin receptor (TfR). SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212691 Cd Length: 52 Bit Score: 46.55 E-value: 1.91e-06

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|..
gi 1804876928 1152 QVIAMYDYVANNEDELNFSKGQLINVLNKDDPDWWQGEINGVTGLFPSNYVK 1203
Cdd:cd11757      1 EVVAIKDYCPTNFTTLKFSKGDHLYVLDTSGGEWWYAHNTTEMGYIPSSYVQ 52

Src homology 3 domain of the Rho guanine nucleotide exchange factor ARHGEF9; ARHGEF9, also called PEM2 or collybistin, selectively activates Cdc42 by exchanging bound GDP for free GTP. It is highly expressed in the brain and it interacts with gephyrin, a postsynaptic protein associated with GABA and glycine receptors. Mutations in the ARHGEF9 gene cause X-linked mental retardation with associated features like seizures, hyper-anxiety, aggressive behavior, and sensory hyperarousal. ARHGEF9 contains a SH3 domain followed by RhoGEF (also called Dbl-homologous or DH) and Pleckstrin Homology (PH) domains. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212908 Cd Length: 62 Bit Score: 46.63 E-value: 1.92e-06

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|
gi 1804876928 1155 AMYDYVANNEDELNFSKGQLINVLNKDDPDWWQGEINGVTGLFPSNYVKM 1204
Cdd:cd11975      9 AVWDHVTMANRELAFKAGDVIKVLDASNKDWWWGQIDDEEGWFPASFVRL 58

First Src Homology 3 domain of SH3 domain containing ring finger 2; SH3RF2 is also called POSHER (POSH-eliminating RING protein) or HEPP1 (heart protein phosphatase 1-binding protein). It acts as an anti-apoptotic regulator of the JNK pathway by binding to and promoting the degradation of SH3RF1 (or POSH), a scaffold protein that is required for pro-apoptotic JNK activation. It may also play a role in cardiac functions together with protein phosphatase 1. SH3RF2 contains an N-terminal RING finger domain and three SH3 domains. This model represents the first SH3 domain, located at the N-terminal half, of SH3RF2. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212862 Cd Length: 54 Bit Score: 46.47 E-value: 1.93e-06

                           10        20        30        40
                   ....*....|....*....|....*....|....*....|....*....
gi 1804876928 1009 ALYSYSSVEPGDLTFIEGEEILV-TQKDGEWWTGSIGDRTGIFPSNYVK 1056
Cdd:cd11929      5 ALCNYRGHNPGDLKFNKGDVILLrRQLDENWYLGEINGVSGIFPASSVE 53

C-terminal (or second) Src homology 3 domain of VAV2 protein; VAV2 is widely expressed and functions as a guanine nucleotide exchange factor (GEF) for RhoA, RhoB and RhoG and also activates Rac1 and Cdc42. It is implicated in many cellular and physiological functions including blood pressure control, eye development, neurite outgrowth and branching, EGFR endocytosis and degradation, and cell cluster morphology, among others. It has been reported to associate with Nek3. VAV proteins contain several domains that enable their function: N-terminal calponin homology (CH), acidic, RhoGEF (also called Dbl-homologous or DH), Pleckstrin Homology (PH), C1 (zinc finger), SH2, and two SH3 domains. The SH3 domain of VAV is involved in the localization of proteins to specific sites within the cell, by interacting with proline-rich sequences within target proteins. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212910 [Multi-domain] Cd Length: 58 Bit Score: 46.54 E-value: 1.98e-06

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|..
gi 1804876928 1154 IAMYDYVANNEDELNFSKGQLINVLNK--DDPDWWQGEINGVTGLFPSNYVK 1203
Cdd:cd11977      4 VARYNFAARDMRELSLREGDVVRIYSRigGDQGWWKGETNGRIGWFPSTYVE 55

Third Src Homology 3 domain (SH3C) of Cbl-interacting protein of 85 kDa; CIN85, also called SH3 domain-containing kinase-binding protein 1 (SH3KBP1) or CD2-binding protein 3 (CD2BP3) or Ruk, is an adaptor protein that is involved in the downregulation of receptor tyrosine kinases by facilitating endocytosis through interaction with endophilin-associated ubiquitin ligase Cbl proteins. It is also important in many other cellular processes including vesicle-mediated transport, cytoskeletal remodelling, apoptosis, cell adhesion and migration, and viral infection, among others. CIN85 exists as multiple variants from alternative splicing; the main variant contains three SH3 domains, a proline-rich region, and a C-terminal coiled-coil domain. All of these domains enable CIN85 to bind various protein partners and assemble complexes that have been implicated in many different functions. This alignment model represents the third SH3 domain (SH3C) of CIN85. SH3C has been shown to bind ubiquitin. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212990 [Multi-domain] Cd Length: 56 Bit Score: 46.43 E-value: 2.01e-06

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|..
gi 1804876928  786 KALYRFEARSHDEMSFNSGDIIQVDEKTIGEPGWLYGSFQGNFGWFPCNYVE 837
Cdd:cd12057      3 KVLFPYEAQNEDELTIKEGDIVTLISKDCIDAGWWEGELNGRRGVFPDNFVK 54

Third (or C-terminal) Src Homology 3 domain of Sorbin and SH3 domain containing 2 (Sorbs2), also called Arg-binding protein 2 (ArgBP2); Sorbs2 or ArgBP2 is an adaptor protein containing one sorbin homology (SoHo) and three SH3 domains. It regulates actin-dependent processes including cell adhesion, morphology, and migration. It is expressed in many tissues and is abundant in the heart. Like vinexin, it is found in focal adhesion where it interacts with vinculin and afadin. It also localizes in epithelial cell stress fibers and in cardiac muscle cell Z-discs. Sorbs2 has been implicated to play roles in the signaling of c-Arg, Akt, and Pyk2. Other interaction partners of Sorbs2 include c-Abl, flotillin, spectrin, dynamin 1/2, synaptojanin, PTP-PEST, among others. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212850 [Multi-domain] Cd Length: 61 Bit Score: 46.52 E-value: 2.03e-06

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....*..
gi 1804876928  785 YKALYRFEARSHDEMSFNSGDIIQVDEKTigEPGWLYGSFQGN--FGWFPCNYVEKM 839
Cdd:cd11917      7 FQALYNYMPRNEDELELREGDVIDVMEKC--DDGWFVGTSRRTkfFGTFPGNYVKRL 61

Second Src Homology 3 domain of Nck1 adaptor protein; Nck1 (also called Nckalpha) plays a crucial role in connecting signaling pathways of tyrosine kinase receptors and important effectors in actin dynamics and cytoskeletal remodeling. It binds and activates RasGAP, resulting in the downregulation of Ras. It is also involved in the signaling of endothilin-mediated inhibition of cell migration. Nck adaptor proteins regulate actin cytoskeleton dynamics by linking proline-rich effector molecules to protein tyrosine kinases and phosphorylated signaling intermediates. They contain three SH3 domains and a C-terminal SH2 domain. They function downstream of the PDGFbeta receptor and are involved in Rho GTPase signaling and actin dynamics. Vertebrates contain two Nck adaptor proteins: Nck1 (also called Nckalpha) and Nck2, which show partly overlapping functions but also bind distinct targets. The second SH3 domain of Nck appears to prefer ligands containing the APxxPxR motif. SH3 domains are protein interaction domains that usually bind to proline-rich ligands with moderate affinity and selectivity, preferentially a PxxP motif. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212834 [Multi-domain] Cd Length: 55 Bit Score: 46.57 E-value: 2.05e-06

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....*
gi 1804876928 1079 AQVTSAYVASGSEQLSLAPGQLILILKKNSSGWWQGELQARgkkrqKGWFPASHV 1133
Cdd:cd11901      4 AYVKFNYTAEREDELSLVKGTKVIVMEKCSDGWWRGSYNGQ-----VGWFPSNYV 53

Second Src Homology 3 domain of Vinexin, also called Sorbin and SH3 domain containing 3 (Sorbs3); Vinexin is also called Sorbs3, SH3P3, and SH3-containing adapter molecule 1 (SCAM-1). It is an adaptor protein containing one sorbin homology (SoHo) and three SH3 domains. Vinexin was first identified as a vinculin binding protein; it is co-localized with vinculin at cell-ECM and cell-cell adhesion sites. There are several splice variants of vinexin: alpha, which contains the SoHo and three SH3 domains and displays tissue-specific expression; and beta, which contains only the three SH3 domains and is widely expressed. Vinexin alpha stimulates the accumulation of F-actin at focal contact sites. Vinexin also promotes keratinocyte migration and wound healing. The SH3 domains of vinexin have been reported to bind a number of ligands including vinculin, WAVE2, DLG5, Abl, and Cbl. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212857 Cd Length: 56 Bit Score: 46.50 E-value: 2.08e-06

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....*
gi 1804876928 1152 QVIAMYDYVANNEDELNFSKGQLINVLNKDDPDWWQGEINGVT--GLFPSNYVKM 1204
Cdd:cd11924      2 EAVAQYTFKGDLEVELSFRKGEHICLIRKVNENWYEGRITGTGrqGIFPASYVQV 56

Coiled-coil domain-containing protein 158; CCDC158 is a family of proteins found in eukaryotes. The function is not known.

Pssm-ID: 464943 [Multi-domain] Cd Length: 1112 Bit Score: 52.81 E-value: 2.09e-06

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1804876928  385 KIQEEEPQ-----KKLPVTFEDKRKANYERGNVElEKRRQALMEQQQREAERKAQKE--KEEWERK----------QREL 447
Cdd:pfam15921  343 KIEELEKQlvlanSELTEARTERDQFSQESGNLD-DQLQKLLADLHKREKELSLEKEqnKRLWDRDtgnsitidhlRREL 421

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1804876928  448 QEQEWKKQlelekRLEKQRELERQREEERRKEIERREAAKQE-LERQRRLEWERIRRQELLNQRNREqeeivrLNSKKks 526
Cdd:pfam15921  422 DDRNMEVQ-----RLEALLKAMKSECQGQMERQMAAIQGKNEsLEKVSSLTAQLESTKEMLRKVVEE------LTAKK-- 488

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1804876928  527 lhLELEALNGKHQQISGRLQDVRLRKQTQKTEIEVLDKQCDLEIMEIKQLQQE---LQDYQNK---LIYLVPEK----QL 596
Cdd:pfam15921  489 --MTLESSERTVSDLTASLQEKERAIEATNAEITKLRSRVDLKLQELQHLKNEgdhLRNVQTEceaLKLQMAEKdkviEI 566

                          250       260       270       280       290       300       310       320
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1804876928  597 LNERIKNM-----QLGNTPdlGIDLLHKKSLEKEELCQR--------LKEQLDALEKETASKLSEMDSfnNQLKCGNMDD 663
Cdd:pfam15921  567 LRQQIENMtqlvgQHGRTA--GAMQVEKAQLEKEINDRRlelqefkiLKDKKDAKIRELEARVSDLEL--EKVKLVNAGS 642

                          330       340       350       360       370       380       390       400
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1804876928  664 SVLQCLLSLLSCLNNLFLLLKELRESYNTQQLALEQLHKIKRDKLKEIERKRSEL---IQKKKLEDEAIR---KAKQGKE 737
Cdd:pfam15921  643 ERLRAVKDIKQERDQLLNEVKTSRNELNSLSEDYEVLKRNFRNKSEEMETTTNKLkmqLKSAQSELEQTRntlKSMEGSD 722

                          410       420
                   ....*....|....*....|....*....
gi 1804876928  738 -NLWRESLRKEEEEKQKRLQEEKTQEKVQ 765
Cdd:pfam15921  723 gHAMKVAMGMQKQITAKRGQIDALQSKIQ 751

Second Src Homology 3 domain of Nck adaptor proteins; Nck adaptor proteins regulate actin cytoskeleton dynamics by linking proline-rich effector molecules to protein tyrosine kinases and phosphorylated signaling intermediates. They contain three SH3 domains and a C-terminal SH2 domain. They function downstream of the PDGFbeta receptor and are involved in Rho GTPase signaling and actin dynamics. Vertebrates contain two Nck adaptor proteins: Nck1 (also called Nckalpha) and Nck2 (also called Nckbeta or Growth factor receptor-bound protein 4, Grb4), which show partly overlapping functions but also bind distinct targets. Their SH3 domains are involved in recruiting downstream effector molecules, such as the N-WASP/Arp2/3 complex, which when activated induces actin polymerization that results in the production of pedestals, or protrusions of the plasma membrane. The second SH3 domain of Nck appears to prefer ligands containing the APxxPxR motif. SH3 domains are protein interaction domains that usually bind to proline-rich ligands with moderate affinity and selectivity, preferentially a PxxP motif. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212700 [Multi-domain] Cd Length: 53 Bit Score: 46.10 E-value: 2.12e-06

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|..
gi 1804876928 1006 EYIALYSYSSVEPGDLTFIEGEEILVTQK--DGeWWTGSIGDRTGIFPSNYV 1055
Cdd:cd11766      1 PAVVKFNYEAQREDELSLRKGDRVLVLEKssDG-WWRGECNGQVGWFPSNYV 51

Src Homology 3 domain of Amphiphysin and related domains; Amphiphysins function primarily in endocytosis and other membrane remodeling events. They exist in several isoforms and mammals possess two amphiphysin proteins from distinct genes. Amphiphysin I proteins, enriched in the brain and nervous system, contain domains that bind clathrin, Adaptor Protein complex 2 (AP2), dynamin, and synaptojanin. They function in synaptic vesicle endocytosis. Human autoantibodies to amphiphysin I hinder GABAergic signaling and contribute to the pathogenesis of paraneoplastic stiff-person syndrome. Some amphiphysin II isoforms, also called Bridging integrator 1 (Bin1), are localized in many different tissues and may function in intracellular vesicle trafficking. In skeletal muscle, Bin1 plays a role in the organization and maintenance of the T-tubule network. Mutations in Bin1 are associated with autosomal recessive centronuclear myopathy. Amphiphysins contain an N-terminal BAR domain with an additional N-terminal amphipathic helix (an N-BAR), a variable central domain, and a C-terminal SH3 domain. The SH3 domain of amphiphysins bind proline-rich motifs present in binding partners such as dynamin, synaptojanin, and nsP3. It also belongs to a subset of SH3 domains that bind ubiquitin in a site that overlaps with the peptide binding site. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212724 [Multi-domain] Cd Length: 64 Bit Score: 46.55 E-value: 2.24e-06

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....*....
gi 1804876928  786 KALYRFEARSHDEMSFNSGDIIQV---DEKTIGEPGWLYGSFQGN--FGWFPCNYVEKM 839
Cdd:cd11790      6 RATHDYTAEDTDELTFEKGDVILVipfDDPEEQDEGWLMGVKESTgcRGVFPENFTERI 64

FYVE, RhoGEF and PH domain containing/faciogenital dysplasia proteins 5 and 6, N-terminal Pleckstrin Homology (PH) domain; FGD5 regulates promotes angiogenesis of vascular endothelial growth factor (VEGF) in vascular endothelial cells, including network formation, permeability, directional movement, and proliferation. The specific function of FGD6 is unknown. In general, FGDs have a RhoGEF (DH) domain, followed by a PH domain, a FYVE domain and a C-terminal PH domain. All FGDs are guanine nucleotide exchange factors that activate the Rho GTPase Cdc42, an important regulator of membrane trafficking. The RhoGEF domain is responsible for GEF catalytic activity, while the PH domain is involved in intracellular targeting of the DH domain. PH domains have diverse functions, but in general are involved in targeting proteins to the appropriate cellular location or in the interaction with a binding partner. They share little sequence conservation, but all have a common fold, which is electrostatically polarized. Less than 10% of PH domains bind phosphoinositide phosphates (PIPs) with high affinity and specificity. PH domains are distinguished from other PIP-binding domains by their specific high-affinity binding to PIPs with two vicinal phosphate groups: PtdIns(3,4)P2, PtdIns(4,5)P2 or PtdIns(3,4,5)P3 which results in targeting some PH domain proteins to the plasma membrane. A few display strong specificity in lipid binding. Any specificity is usually determined by loop regions or insertions in the N-terminus of the domain, which are not conserved across all PH domains. PH domains are found in cellular signaling proteins such as serine/threonine kinase, tyrosine kinases, regulators of G-proteins, endocytotic GTPases, adaptors, as well as cytoskeletal associated molecules and in lipid associated enzymes.

Pssm-ID: 275424 Cd Length: 124 Bit Score: 48.42 E-value: 2.26e-06

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1804876928 1454 RKLLHSGKLYKTkSNKEL---HGFLFNDFLLLTYMVKqfavssgseklfsskSNAQFKMYKTPIFLNeVLVKLPTDPS-S 1529
Cdd:cd13389     12 RKLIKEGELMKV-SRKEMqprYFFLFNDCLLYTTPVQ---------------SSGMLKLNNELPLSG-MKVKLPEDEEyS 74

                           90       100       110       120
                   ....*....|....*....|....*....|....*....|....*.
gi 1804876928 1530 DEpvFHISHIDRVYTLRTDNINERTAWVQKIKAASEQYidteKKKR 1575
Cdd:cd13389     75 NE--FQIISTKRSFTLIASSEEERDEWVKALSRAIEEH----TKKQ 114

Src homology 3 domains of the p47phox subunit of NADPH oxidase and similar domains; This family is composed of the tandem SH3 domains of p47phox subunit of NADPH oxidase and Nox Organizing protein 1 (NoxO1), the four SH3 domains of Tks4 (Tyr kinase substrate with four SH3 domains), the five SH3 domains of Tks5, the SH3 domain of obscurin, Myosin-I, and similar domains. Most members of this group also contain Phox homology (PX) domains, except for obscurin and Myosin-I. p47phox and NoxO1 are regulators of the phagocytic NADPH oxidase complex (also called Nox2 or gp91phox) and nonphagocytic NADPH oxidase Nox1, respectively. They play roles in the activation of their respective NADPH oxidase, which catalyzes the transfer of electrons from NADPH to molecular oxygen to form superoxide. Tks proteins are Src substrates and scaffolding proteins that play important roles in the formation of podosomes and invadopodia, the dynamic actin-rich structures that are related to cell migration and cancer cell invasion. Obscurin is a giant muscle protein that plays important roles in the organization and assembly of the myofibril and the sarcoplasmic reticulum. Type I myosins (Myosin-I) are actin-dependent motors in endocytic actin structures and actin patches. They play roles in membrane traffic in endocytic and secretory pathways, cell motility, and mechanosensing. Myosin-I contains an N-terminal actin-activated ATPase, a phospholipid-binding TH1 (tail homology 1) domain, and a C-terminal extension which includes an F-actin-binding TH2 domain, an SH3 domain, and an acidic peptide that participates in activating the Arp2/3complex. The SH3 domain of myosin-I is required for myosin-I-induced actin polymerization. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212790 [Multi-domain] Cd Length: 53 Bit Score: 46.09 E-value: 2.29e-06

                           10        20        30        40
                   ....*....|....*....|....*....|....*....|....*....
gi 1804876928  926 ALCSWTAKKDNHLNFSKHDIITVLEQQEN-WWFGEVHGGRGWFPKSYVK 973
Cdd:cd11856      4 AIADYEAQGDDEISLQEGEVVEVLEKNDSgWWYVRKGDKEGWVPASYLE 52

Third (or C-terminal) Src Homology 3 domain of Vinexin, also called Sorbin and SH3 domain containing 3 (Sorbs3); Vinexin is also called Sorbs3, SH3P3, and SH3-containing adapter molecule 1 (SCAM-1). It is an adaptor protein containing one sorbin homology (SoHo) and three SH3 domains. Vinexin was first identified as a vinculin binding protein; it is co-localized with vinculin at cell-ECM and cell-cell adhesion sites. There are several splice variants of vinexin: alpha, which contains the SoHo and three SH3 domains and displays tissue-specific expression; and beta, which contains only the three SH3 domains and is widely expressed. Vinexin alpha stimulates the accumulation of F-actin at focal contact sites. Vinexin also promotes keratinocyte migration and wound healing. The SH3 domains of vinexin have been reported to bind a number of ligands including vinculin, WAVE2, DLG5, Abl, and Cbl. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212851 [Multi-domain] Cd Length: 58 Bit Score: 46.49 E-value: 2.38e-06

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....
gi 1804876928  785 YKALYRFEARSHDEMSFNSGDIIQVDEKTigEPGWLYGSFQGN--FGWFPCNYV 836
Cdd:cd11918      4 YKAVYQYRPQNEDELELREGDRVDVMQQC--DDGWFVGVSRRTqkFGTFPGNYV 55

Second C-terminal Src homology 3 domain of Fungal Actin-binding protein 1; Abp1 is an adaptor protein that functions in receptor-mediated endocytosis and vesicle trafficking. It contains an N-terminal actin-binding module, the actin-depolymerizing factor (ADF) homology domain, a central proline-rich region, and a C-terminal SH3 domain (many yeast Abp1 proteins contain two C-terminal SH3 domains). Yeast Abp1 also contains two acidic domains that bind directly to the Arp2/3 complex, which is required to initiate actin polymerization. The SH3 domain of yeast Abp1 binds and localizes the kinases, Ark1p and Prk1p, which facilitate actin patch disassembly following vesicle internalization. It also mediates the localization to the actin patch of the synaptojanin-like protein, Sjl2p, which plays a key role in endocytosis. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212894 [Multi-domain] Cd Length: 53 Bit Score: 45.98 E-value: 2.52e-06

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|...
gi 1804876928  786 KALYRFEARSHDEMSFNSGD-IIQVDektIGEPGWLYGSFQGNFGWFPCNYVE 837
Cdd:cd11961      3 KALYDYDAAEDNELSFFENDkIINIE---FVDDDWWLGECHGSRGLFPSNYVE 52

Src homology 3 domain of Signal Transducing Adaptor Molecule 1; STAM1 is part of the endosomal sorting complex required for transport (ESCRT-0) and is involved in sorting ubiquitinated cargo proteins from the endosome. It may also be involved in the regulation of IL2 and GM-CSF mediated signaling, and has been implicated in neural cell survival. STAMs were discovered as proteins that are highly phosphorylated following cytokine and growth factor stimulation. They function in cytokine signaling and surface receptor degradation, as well as regulate Golgi morphology. They associate with many proteins including Jak2 and Jak3 tyrosine kinases, Hrs, AMSH, and UBPY. STAM adaptor proteins contain VHS (Vps27, Hrs, STAM homology), ubiquitin interacting (UIM), and SH3 domains. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212897 [Multi-domain] Cd Length: 55 Bit Score: 46.10 E-value: 2.59e-06

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|.
gi 1804876928  786 KALYRFEARSHDEMSFNSGDIIQVDEKTigEPGWLYGSFQGNFGWFPCNYV 836
Cdd:cd11964      4 RAIYDFEAAEDNELTFKAGDIITILDDS--DPNWWKGETPQGTGLFPSNFV 52

Src Homology 3 domain of Membrane Protein, Palmitoylated 1 (or MAGUK p55 subfamily member 1); MPP1, also called 55 kDa erythrocyte membrane protein (p55), is a ubiquitously-expressed scaffolding protein that plays roles in regulating neutrophil polarity, cell shape, hair cell development, and neural development and patterning of the retina. It was originally identified as an erythrocyte protein that stabilizes the actin cytoskeleton to the plasma membrane by forming a complex with 4.1R protein and glycophorin C. MPP1 is one of seven vertebrate homologs of the Drosophila Stardust protein, which is required in establishing cell polarity, and it contains the three domains characteristic of MAGUK (membrane-associated guanylate kinase) proteins: PDZ, SH3, and guanylate kinase (GuK). In addition, it also contains the Hook (Protein 4.1 Binding) motif in between the SH3 and GuK domains. The GuK domain in MAGUK proteins is enzymatically inactive; instead, the domain mediates protein-protein interactions and associates intramolecularly with the SH3 domain. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 213013 Cd Length: 62 Bit Score: 46.49 E-value: 2.63e-06

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....*.
gi 1804876928 1155 AMYDY-------VANNEDELNFSKGQLINVLNKDDPDWWQGEINGV----TGLFPS 1199
Cdd:cd12080      4 AQFDYdpkkdnlIPCKEAGLKFQTGDIIQIINKDDSNWWQGRVEGSgeesAGLIPS 59

Src homology 3 domain of an unknown subfamily of proteins with similarity to Protein kinase C and Casein kinase Substrate in Neurons (PACSIN) proteins; PACSINs, also called Synaptic dynamin-associated proteins (Syndapins), act as regulators of cytoskeletal and membrane dynamics. They bind both dynamin and Wiskott-Aldrich syndrome protein (WASP), and may provide direct links between the actin cytoskeletal machinery through WASP and dynamin-dependent endocytosis. Vetebrates harbor three isoforms with distinct expression patterns and specific functions. PACSINs contain an N-terminal F-BAR domain and a C-terminal SH3 domain. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212932 [Multi-domain] Cd Length: 56 Bit Score: 46.09 E-value: 2.63e-06

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|...
gi 1804876928 1152 QVIAMYDYVANNEDELNFSKGQ-LINVLNKDDPDWWQGEIN-GVTGLFPSNYV 1202
Cdd:cd11999      3 RVRAVYDYTGQEPDELSFKAGEeLLKVEDEDEQGWCKGVTDgGAVGLYPANYV 55

C-terminal (or second) Src homology 3 domain of VAV1 protein; VAV1 is expressed predominantly in the hematopoietic system and it plays an important role in the development and activation of B and T cells. It is activated by tyrosine phosphorylation to function as a guanine nucleotide exchange factor (GEF) for Rho GTPases following cell surface receptor activation, triggering various effects such as cytoskeletal reorganization, transcription regulation, cell cycle progression, and calcium mobilization. It also serves as a scaffold protein and has been shown to interact with Ku70, Socs1, Janus kinase 2, SIAH2, S100B, Abl gene, ZAP-70, SLP76, and Syk, among others. VAV proteins contain several domains that enable their function: N-terminal calponin homology (CH), acidic, RhoGEF (also called Dbl-homologous or DH), Pleckstrin Homology (PH), C1 (zinc finger), SH2, and two SH3 domains. The C-terminal SH3 domain of Vav1 interacts with a wide variety of proteins including cytoskeletal regulators (zyxin), RNA-binding proteins (Sam68), transcriptional regulators, viral proteins, and dynamin 2. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212909 [Multi-domain] Cd Length: 54 Bit Score: 46.09 E-value: 2.69e-06

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|..
gi 1804876928  924 AQALCSWTAKKDNHLNFSKHDIITVLEQ--QENWWFGEVHGGRGWFPKSYVK 973
Cdd:cd11976      2 AKARYDFCARDRSELSLKEGDIIKILNKkgQQGWWRGEIYGRVGWFPANYVE 53

Src homology 3 domain of Phospholipase C (PLC) gamma; PLC catalyzes the hydrolysis of phosphatidylinositol (4,5)-bisphosphate [PtdIns(4,5)P2] to produce Ins(1,4,5)P3 and diacylglycerol (DAG) in response to various receptors. Ins(1,4,5)P3 initiates the calcium signaling cascade while DAG functions as an activator of PKC. PLCgamma catalyzes this reaction in tyrosine kinase-dependent signaling pathways. It is activated and recruited to its substrate at the membrane. Vertebrates contain two forms of PLCgamma, PLCgamma1, which is widely expressed, and PLCgamma2, which is primarily found in haematopoietic cells. PLCgamma contains a Pleckstrin homology (PH) domain followed by an elongation factor (EF) domain, two catalytic regions of PLC domains that flank two tandem SH2 domains, followed by a SH3 domain and C2 domain. The SH3 domain of PLCgamma1 directly interacts with dynamin-1 and can serve as a guanine nucleotide exchange factor (GEF). It also interacts with Cbl, inhibiting its phosphorylation and activity. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212759 [Multi-domain] Cd Length: 54 Bit Score: 46.17 E-value: 2.78e-06

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|
gi 1804876928 1009 ALYSYSSVEPGDLTFIEGEEIL-VTQKDGEWWTGSIGDR-TGIFPSNYVK 1056
Cdd:cd11825      4 ALYDYRAQRPDELSFCKHAIITnVEKEDGGWWRGDYGGKkQKWFPANYVE 53

Fifth Src homology 3 domain of ADAM-binding protein Eve-1; Eve-1, also called SH3 domain-containing protein 19 (SH3D19) or EEN-binding protein (EBP), exists in multiple alternatively spliced isoforms. The longest isoform contains five SH3 domain in the C-terminal region and seven proline-rich motifs in the N-terminal region. It is abundantly expressed in skeletal muscle and heart, and may be involved in regulating the activity of ADAMs (A disintegrin and metalloproteases). Eve-1 interacts with EEN, an endophilin involved in endocytosis and may be the target of the MLL-EEN fusion protein that is implicated in leukemogenesis. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212752 [Multi-domain] Cd Length: 50 Bit Score: 45.94 E-value: 2.87e-06

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....
gi 1804876928  786 KALYRFEARSHDEMSFNSGDII----QVDEKtigepgWLYGSFQGNFGWFPCNY 835
Cdd:cd11818      3 RALYDFTGENEDELSFKAGDIIteleSIDEE------WMSGELRGKSGIFPKNF 50

Src Homology 3 domain of Pak Interactive eXchange factors; PIX proteins are Rho guanine nucleotide exchange factors (GEFs), which activate small GTPases by exchanging bound GDP for free GTP. They act as GEFs for both Cdc42 and Rac 1, and have been implicated in cell motility, adhesion, neurite outgrowth, and cell polarity. Vertebrates contain two proteins from the PIX subfamily, alpha-PIX and beta-PIX. Alpha-PIX, also called ARHGEF6, is localized in dendritic spines where it regulates spine morphogenesis. Mutations in the ARHGEF6 gene cause X-linked intellectual disability in humans. Beta-PIX play roles in regulating neuroendocrine exocytosis, focal adhesion maturation, cell migration, synaptic vesicle localization, and insulin secretion. PIX proteins contain an N-terminal SH3 domain followed by RhoGEF (also called Dbl-homologous or DH) and Pleckstrin Homology (PH) domains, and a C-terminal leucine-zipper domain for dimerization. The SH3 domain of PIX binds to an atypical PxxxPR motif in p21-activated kinases (PAKs) with high affinity. The binding of PAKs to PIX facilitate the localization of PAKs to focal complexes and also localizes PAKs to PIX targets Cdc43 and Rac, leading to the activation of PAKs. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212810 [Multi-domain] Cd Length: 53 Bit Score: 45.77 E-value: 2.89e-06

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....*...
gi 1804876928 1078 IAQVTSAYVASGSEQLSLAPGQLILILKKNSSGWWQGELQARgkkrqKGWFPASHVKL 1135
Cdd:cd11877      1 LVRAKFNFEGTNEDELSFDKGDIITVTQVVEGGWWEGTLNGK-----TGWFPSNYVKE 53

Domain of unknown function (DUF4670); This family of proteins is found in eukaryotes. Proteins in this family are typically between 373 and 763 amino acids in length.

Pssm-ID: 464815 [Multi-domain] Cd Length: 522 Bit Score: 51.88 E-value: 2.90e-06

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1804876928  388 EEEPQKKLPVTFEDKRKANYERGNVELEKRRQALMEQQQREaerKAQKEKEEWERKQRELQEQewKKQLELEK-RLEKQR 466
Cdd:pfam15709  379 ELEQQRRFEEIRLRKQRLEEERQRQEEEERKQRLQLQAAQE---RARQQQEEFRRKLQELQRK--KQQEEAERaEAEKQR 453

                           90       100       110       120       130
                   ....*....|....*....|....*....|....*....|....*....|....
gi 1804876928  467 ELERQREEERRKEIERREAAKQELERQRRLEWERIRRQELLNQRNREQEEIVRL 520
Cdd:pfam15709  454 QKELEMQLAEEQKRLMEMAEEERLEYQRQKQEAEEKARLEAEERRQKEEEAARL 507

Src Homology 3 domain of Nephrocystin (or Nephrocystin-1); Nephrocystin contains an SH3 domain involved in signaling pathways that regulate cell adhesion and cytoskeletal organization. It is a protein that in humans is associated with juvenile nephronophthisis, an inherited kidney disease characterized by renal fibrosis that lead to chronic renal failure in children. It is localized in cell-cell junctions in renal duct cells, and is known to interact with Ack1, an activated Cdc42-associated kinase. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212704 [Multi-domain] Cd Length: 54 Bit Score: 45.77 E-value: 3.27e-06

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|...
gi 1804876928 1153 VIAMYDYVANNEDELNFSKGQLINVLNKDDPDWWQGE-INGVTGLFPSNYVKM 1204
Cdd:cd11770      2 YEALSDFQAEQEGDLSFKKGEVLRIISKRADGWWLAEnSKGNRGLVPKTYLKV 54

Third Src Homology 3 domain of SH3 domain containing ring finger 2; SH3RF2 is also called POSHER (POSH-eliminating RING protein) or HEPP1 (heart protein phosphatase 1-binding protein). It acts as an anti-apoptotic regulator of the JNK pathway by binding to and promoting the degradation of SH3RF1 (or POSH), a scaffold protein that is required for pro-apoptotic JNK activation. It may also play a role in cardiac functions together with protein phosphatase 1. SH3RF2 contains an N-terminal RING finger domain and three SH3 domains. This model represents the third SH3 domain, located in the middle, of SH3RF2. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212718 Cd Length: 55 Bit Score: 45.92 E-value: 3.29e-06

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....*...
gi 1804876928 1007 YIALYSYSSVEPGDLTFIEGEEILVTQKDGEWW-------TGsigdRTGIFPSNYVKP 1057
Cdd:cd11784      2 CVALHSYSAHRPEELELQKGEGVRVLGKFQEGWlrglslvTG----RVGIFPSNYVSP 55

First Src homology 3 domain (or SH3A) of Intersectin; Intersectins (ITSNs) are adaptor proteins that function in exo- and endocytosis, actin cytoskeletal reorganization, and signal transduction. They are essential for initiating clathrin-coated pit formation. They bind to many proteins through their multidomain structure and facilitate the assembly of multimeric complexes. Vertebrates contain two ITSN proteins, ITSN1 and ITSN2, which exist in alternatively spliced short and long isoforms. The short isoforms contain two Eps15 homology domains (EH1 and EH2), a coiled-coil region and five SH3 domains (SH3A-E), while the long isoforms, in addition, contain RhoGEF (also called Dbl-homologous or DH), Pleckstrin homology (PH) and C2 domains. ITSN1 and ITSN2 are both widely expressed, with variations depending on tissue type and stage of development. The first SH3 domain (or SH3A) of ITSN1 has been shown to bind many proteins including Sos1, dynamin1/2, CIN85, c-Cbl, PI3K-C2, SHIP2, N-WASP, and CdGAP, among others. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212770 [Multi-domain] Cd Length: 55 Bit Score: 45.81 E-value: 3.35e-06

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|..
gi 1804876928 1007 YIALYSYSSVEPGDLTFIEGEEILVTQKD-GE--WWTGSIGDRTGIFPSNYV 1055
Cdd:cd11836      2 YRALYAFEARNPDEISFQPGDIIQVDESQvAEpgWLAGELKGKTGWFPANYV 53

Second Src Homology 3 domain of FCH and double SH3 domains protein 1; FCHSD1 has a domain structure consisting of an N-terminal F-BAR (FES-CIP4 Homology and Bin/Amphiphysin/Rvs), two SH3, and C-terminal proline-rich domains. It has only been characterized in silico and its function is unknown. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212828 Cd Length: 58 Bit Score: 46.11 E-value: 3.37e-06

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|...
gi 1804876928 1155 AMYDYVANNEDELNFSKGQLINVLNKD----DPDWWQGEINGVTGLFPSNYVK 1203
Cdd:cd11895      4 ALYSYTGQSPEELSFPEGALIRLLPRAqdgvDDGFWRGEFGGRVGVFPSLLVE 56

Src homology 3 domain of Cortactin; Cortactin was originally identified as a substrate of Src kinase. It is an actin regulatory protein that binds to the Arp2/3 complex and stabilizes branched actin filaments. It is involved in cellular processes that affect cell motility, adhesion, migration, endocytosis, and invasion. It is expressed ubiquitously except in hematopoietic cells, where the homolog hematopoietic lineage cell-specific 1 (HS1) is expressed instead. Cortactin contains an N-terminal acidic domain, several copies of a repeat domain found in cortactin and HS1, a proline-rich region, and a C-terminal SH3 domain. The N-terminal region interacts with the Arp2/3 complex and F-actin, and is crucial in regulating branched actin assembly. Cortactin also serves as a scaffold and provides a bridge to the actin cytoskeleton for membrane trafficking and signaling proteins that bind to its SH3 domain. Binding partners for the SH3 domain of cortactin include dynamin2, N-WASp, MIM, FGD1, among others. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212892 [Multi-domain] Cd Length: 53 Bit Score: 45.87 E-value: 3.40e-06

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|..
gi 1804876928  924 AQALCSWTAKKDNHLNFSKHDIITVLEQ-QENWWFGEVHGGRGWFPKSYVKI 974
Cdd:cd11959      2 AVALYDYQAADDDEISFDPDDIITNIEMiDEGWWRGVCRGKYGLFPANYVEL 53

Myosin tail; The myosin molecule is a multi-subunit complex made up of two heavy chains and four light chains it is a fundamental contractile protein found in all eukaryote cell types. This family consists of the coiled-coil myosin heavy chain tail region. The coiled-coil is composed of the tail from two molecules of myosin. These can then assemble into the macromolecular thick filament. The coiled-coil region provides the structural backbone the thick filament.

Pssm-ID: 460256 [Multi-domain] Cd Length: 1081 Bit Score: 52.10 E-value: 3.54e-06

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1804876928  415 EKRRQALMEQQQREAERKAQKEKE--EWERKQRELQEQewkkqlelEKRLEKQRELERQREEERRKEIERREAAKQELER 492
Cdd:pfam01576    4 EEEMQAKEEELQKVKERQQKAESElkELEKKHQQLCEE--------KNALQEQLQAETELCAEAEEMRARLAARKQELEE 75

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1804876928  493 -----QRRLEWERIRRQELLNQRNREQEEIVRLNSkkkslHLELEalngkhqqisgrlQDVRLRKQTQKTEIEVLDKQCD 567
Cdd:pfam01576   76 ilhelESRLEEEEERSQQLQNEKKKMQQHIQDLEE-----QLDEE-------------EAARQKLQLEKVTTEAKIKKLE 137

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1804876928  568 LEIMeikqlqqELQDYQNKLIylvPEKQLLNERIKNMqlgnTPDLGIDLLHKKSLEK---------EELCQRL-KEQLDA 637
Cdd:pfam01576  138 EDIL-------LLEDQNSKLS---KERKLLEERISEF----TSNLAEEEEKAKSLSKlknkheamiSDLEERLkKEEKGR 203

                          250       260       270       280       290       300       310       320
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1804876928  638 LEKETASKLSEMDSFNNQLKCGNMDDSVLQCLLSLLSCLNNLFLLLKELRESYNTQQLALEqlhkikrdKLKEIERKRSE 717
Cdd:pfam01576  204 QELEKAKRKLEGESTDLQEQIAELQAQIAELRAQLAKKEEELQAALARLEEETAQKNNALK--------KIRELEAQISE 275

                          330       340       350       360       370       380       390
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|.
gi 1804876928  718 LIQKKKLEDEAIRKAKQGKENLWRE--SLRKE-----------EEEKQKRLQEEKTQEKVQEEERKVEEKQ 775
Cdd:pfam01576  276 LQEDLESERAARNKAEKQRRDLGEEleALKTEledtldttaaqQELRSKREQEVTELKKALEEETRSHEAQ 346

Third Src Homology 3 domain (SH3C) of CD2-associated protein; CD2AP, also called CMS (Cas ligand with Multiple SH3 domains) or METS1 (Mesenchyme-to-Epithelium Transition protein with SH3 domains), is a cytosolic adaptor protein that plays a role in regulating the cytoskeleton. It is critical in cell-to-cell union necessary for kidney function. It also stabilizes the contact between a T cell and antigen-presenting cells. It is primarily expressed in podocytes at the cytoplasmic face of the slit diaphragm and serves as a linker anchoring podocin and nephrin to the actin cytoskeleton. CD2AP contains three SH3 domains, a proline-rich region, and a C-terminal coiled-coil domain. All of these domains enable CD2AP to bind various protein partners and assemble complexes that have been implicated in many different functions. This alignment model represents the third SH3 domain (SH3C) of CD2AP. SH3C has been shown to bind ubiquitin. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212989 [Multi-domain] Cd Length: 57 Bit Score: 45.97 E-value: 3.55e-06

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|
gi 1804876928 1009 ALYSYSSVEPGDLTFIEGEEILVTQKD-GE--WWTGSIGDRTGIFPSNYV 1055
Cdd:cd12056      6 ALFHYEGTNEDELDFKEGEIILIISKDtGEpgWWKGELNGKEGVFPDNFV 55

First Src Homology 3 domain of SH3 domain containing ring finger protein 1, an E3 ubiquitin-protein ligase; SH3RF1 is also called POSH (Plenty of SH3s) or SH3MD2 (SH3 multiple domains protein 2). It is a scaffold protein that acts as an E3 ubiquitin-protein ligase. It plays a role in calcium homeostasis through the control of the ubiquitin domain protein Herp. It may also have a role in regulating death receptor mediated and JNK mediated apoptosis. SH3RF1 also enhances the ubiquitination of ROMK1 potassium channel resulting in its increased endocytosis. It contains an N-terminal RING finger domain and four SH3 domains. This model represents the first SH3 domain, located at the N-terminal half, of SH3RF1. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212860 Cd Length: 54 Bit Score: 45.71 E-value: 3.56e-06

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....*.
gi 1804876928  786 KALYRFEARSHDEMSFNSGDII----QVDEKtigepgWLYGSFQGNFGWFPCNYVE 837
Cdd:cd11927      4 KALYNYEGKEPGDLKFSKGDIIilrrQVDEN------WYHGEVNGIHGFFPTNFVQ 53

Third (or C-terminal) Src Homology 3 domain of Sorbin and SH3 domain containing 2 (Sorbs2), also called Arg-binding protein 2 (ArgBP2); Sorbs2 or ArgBP2 is an adaptor protein containing one sorbin homology (SoHo) and three SH3 domains. It regulates actin-dependent processes including cell adhesion, morphology, and migration. It is expressed in many tissues and is abundant in the heart. Like vinexin, it is found in focal adhesion where it interacts with vinculin and afadin. It also localizes in epithelial cell stress fibers and in cardiac muscle cell Z-discs. Sorbs2 has been implicated to play roles in the signaling of c-Arg, Akt, and Pyk2. Other interaction partners of Sorbs2 include c-Abl, flotillin, spectrin, dynamin 1/2, synaptojanin, PTP-PEST, among others. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212850 [Multi-domain] Cd Length: 61 Bit Score: 45.75 E-value: 3.69e-06

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|.
gi 1804876928 1155 AMYDYVANNEDELNFSKGQLINVLNKDDPDWWQGEINGVT--GLFPSNYVK 1203
Cdd:cd11917      9 ALYNYMPRNEDELELREGDVIDVMEKCDDGWFVGTSRRTKffGTFPGNYVK 59

Src Homology 3 domain of Class A and B Dedicator of Cytokinesis proteins; DOCK proteins are atypical guanine nucleotide exchange factors (GEFs) that lack the conventional Dbl homology (DH) domain. They are divided into four classes (A-D) based on sequence similarity and domain architecture: class A includes Dock1, 2 and 5; class B includes Dock3 and 4; class C includes Dock6, 7, and 8; and class D includes Dock9, 10 and 11. All DOCKs contain two homology domains: the DHR-1 (Dock homology region-1), also called CZH1 (CED-5, Dock180, and MBC-zizimin homology 1), and DHR-2 (also called CZH2 or Docker). The DHR-1 domain binds phosphatidylinositol-3,4,5-triphosphate while DHR-2 contains the catalytic activity for Rac and/or Cdc42. This subfamily includes only Class A and B DOCKs, which also contain an SH3 domain at the N-terminal region and a PxxP motif at the C-terminus. Class A/B DOCKs are mostly specific GEFs for Rac, except Dock4 which activates the Ras family GTPase Rap1, probably indirectly through interaction with Rap regulatory proteins. The SH3 domain of class A/B DOCKs have been shown to bind Elmo, a scaffold protein that promotes GEF activity of DOCKs by releasing DHR-2 autoinhibition by the intramolecular SH3 domain. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212805 [Multi-domain] Cd Length: 56 Bit Score: 45.65 E-value: 3.69e-06

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|..
gi 1804876928  926 ALCSWTAKKDNHLNFSKHDIITVLEQQENWWFGEV---HGGRGWFPKSYVKI 974
Cdd:cd11872      4 AIYNFQGDGEHQLSLQVGDTVQILEECEGWYRGFSlrnKSLKGIFPKSYVHI 55

N-terminal Src homology 3 domain of GRB2-related adaptor protein 2; GRAP2 is also called GADS (GRB2-related adapter downstream of Shc), GrpL, GRB2L, Mona, or GRID (Grb2-related protein with insert domain). It is expressed specifically in the hematopoietic system. It plays an important role in T cell receptor (TCR) signaling by promoting the formation of the SLP-76:LAT complex, which couples the TCR to the Ras pathway. It also have roles in antigen-receptor and tyrosine kinase mediated signaling. GRAP2 is unique from other GRB2-like adaptor proteins in that it can be regulated by caspase cleavage. It contains an N-terminal SH3 domain, a central SH2 domain, and a C-terminal SH3 domain. The N-terminal SH3 domain of the related protein GRB2 binds to Sos and Sos-derived proline-rich peptides. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212880 [Multi-domain] Cd Length: 52 Bit Score: 45.56 E-value: 3.69e-06

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|..
gi 1804876928  923 KAQALCSWTAKKDNHLNFSKHDIITVLEQQENWWFGEVHGGRGWFPKSYVKI 974
Cdd:cd11947      1 EARGKFDFTASGEDELSFKKGDVLKILSSDDIWFKAELNGEEGYVPKNFVDI 52

Src homology 3 domain of Hematopoietic lineage cell-specific protein 1; HS1, also called HCLS1 (hematopoietic cell-specific Lyn substrate 1), is a cortactin homolog expressed specifically in hematopoietic cells. It is an actin regulatory protein that binds the Arp2/3 complex and stabilizes branched actin filaments. It is required for cell spreading and signaling in lymphocytes. It regulates cytoskeletal remodeling that controls lymphocyte trafficking, and it also affects tissue invasion and infiltration of leukemic B cells. Like cortactin, HS1 contains an N-terminal acidic domain, several copies of a repeat domain found in cortactin and HS1, a proline-rich region, and a C-terminal SH3 domain. The N-terminal region binds the Arp2/3 complex and F-actin, while the C-terminal region acts as an adaptor or scaffold that can connect varied proteins that bind the SH3 domain within the actin network. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 213006 [Multi-domain] Cd Length: 55 Bit Score: 45.59 E-value: 4.04e-06

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|..
gi 1804876928  924 AQALCSWTAKKDNHLNFSKHDIITVLEQ-QENWWFGEVHGGRGWFPKSYVKI 974
Cdd:cd12073      3 AVALYDYQGEGDDEISFDPQETITDIEMvDEGWWKGTCHGHRGLFPANYVEL 54

Src homology 3 domain of Proline-Serine-Threonine Phosphatase-Interacting Protein 1; PSTPIP1, also called CD2 Binding Protein 1 (CD2BP1), is mainly expressed in hematopoietic cells. It is a binding partner of the cell surface receptor CD2 and PTP-PEST, a tyrosine phosphatase which functions in cell motility and Rac1 regulation. It also plays a role in the activation of the Wiskott-Aldrich syndrome protein (WASP), which couples actin rearrangement and T cell activation. Mutations in the gene encoding PSTPIP1 cause the autoinflammatory disorder known as PAPA (pyogenic sterile arthritis, pyoderma gangrenosum, and acne) syndrome. PSTPIP1 contains an N-terminal F-BAR domain, PEST motifs, and a C-terminal SH3 domain. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212758 [Multi-domain] Cd Length: 53 Bit Score: 45.44 E-value: 4.35e-06

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|...
gi 1804876928  923 KAQALCSWTAKKDNHLNFSKHDIITVLEQQEN-WWFGEVHGGRGWFPKSYVKI 974
Cdd:cd11824      1 KYSVLYDYTAQEDDELSISKGDVVAVIEKGEDgWWTVERNGQKGLVPGTYLEK 53

Src Homology 3 domain of fungal peroxisomal membrane protein Pex13p; Pex13p, located in the peroxisomal membrane, contains two transmembrane regions and a C-terminal SH3 domain. It binds to the peroxisomal targeting type I (PTS1) receptor Pex5p and the docking factor Pex14p through its SH3 domain. It is essential for both PTS1 and PTS2 protein import pathways into the peroxisomal matrix. Pex13p binds Pex14p, which contains a PxxP motif, in a classical fashion to the proline-rich ligand binding site of its SH3 domain. It binds the WxxxF/Y motif of Pex5p in a novel site that does not compete with Pex14p binding. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212705 [Multi-domain] Cd Length: 60 Bit Score: 45.73 E-value: 4.41e-06

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....*..
gi 1804876928  786 KALYRFEARSHD-EMSFNSGDIIQVDEKT--IGEP-GWLYGSFQ-GNFGWFPCNYVE 837
Cdd:cd11771      3 RALYDFTPENPEmELSLKKGDIVAVLSKTdpLGRDsEWWKGRTRdGRIGWFPSNYVE 59

Src homology 3 domain of APC-Stimulated guanine nucleotide Exchange Factor 2; ASEF2, also called Spermatogenesis-associated protein 13 (SPATA13), is a GEF that localizes with actin at the leading edge of cells and is important in cell migration and adhesion dynamics. GEFs activate small GTPases by exchanging bound GDP for free GTP. ASEF2 can activate both Rac 1 and Cdc42, but only Rac1 activation is necessary for increased cell migration and adhesion turnover. Together with APC (adenomatous polyposis coli) and Neurabin2, a scaffold protein that binds F-actin, it is involved in regulating HGF-induced cell migration. ASEF2 contains a SH3 domain followed by RhoGEF (also called Dbl-homologous or DH) and Pleckstrin Homology (PH) domains. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212907 Cd Length: 54 Bit Score: 45.44 E-value: 4.64e-06

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|..
gi 1804876928  924 AQALCSWTAKKDNHLNFSKHDIITVLE-QQENWWFGEVHGGRGWFPKSYVKI 974
Cdd:cd11974      3 AEALWDHVTMDDQELAFKAGDVIRVLEaSNKDWWWGRNEDREAWFPASFVRL 54

Src Homology 3 domain of TXK, also called Resting lymphocyte kinase (Rlk); TXK is a cytoplasmic (or nonreceptor) tyr kinase containing Src homology protein interaction domains (SH3, SH2) N-terminal to the catalytic tyr kinase domain. It also contains an N-terminal cysteine-rich region. Rlk is expressed in T-cells and mast cell lines, and is a key component of T-cell receptor (TCR) signaling. It is important in TCR-stimulated proliferation, IL-2 production and phospholipase C-gamma1 activation. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212840 [Multi-domain] Cd Length: 55 Bit Score: 45.33 E-value: 4.66e-06

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|..
gi 1804876928 1152 QVIAMYDYVANNEDELNFSKGQLINVLNKDDPDWWQGEIN-GVTGLFPSNYV 1202
Cdd:cd11907      2 QVKALYDFLPREPSNLALKRAEEYLILEQYDPHWWKARDRyGNEGLIPSNYV 53

Third Src Homology 3 domain of SH3 domain containing ring finger 1 (SH3RF1), SH3RF3, and similar domains; SH3RF1 (or POSH) and SH3RF3 (or POSH2) are scaffold proteins that function as E3 ubiquitin-protein ligases. They contain an N-terminal RING finger domain and four SH3 domains. This model represents the third SH3 domain, located in the middle of SH3RF1 and SH3RF3, and similar domains. SH3RF1 plays a role in calcium homeostasis through the control of the ubiquitin domain protein Herp. It may also have a role in regulating death receptor mediated and JNK mediated apoptosis. SH3RF3 interacts with p21-activated kinase 2 (PAK2) and GTP-loaded Rac1. It may play a role in regulating JNK mediated apoptosis in certain conditions. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212717 [Multi-domain] Cd Length: 55 Bit Score: 45.46 E-value: 4.79e-06

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|...
gi 1804876928 1153 VIAMYDYVANNEDELNFSKGQLINVLNKDDPDWWQGE--INGVTGLFPSNYVK 1203
Cdd:cd11783      2 YVALYPYKPQKPDELELRKGEMYTVTEKCQDGWFKGTslRTGQSGVFPGNYVQ 54

Third Src homology 3 domain of Rab3-interacting molecules (RIMs) binding proteins; RIMs binding proteins (RBPs, RIM-BPs) associate with calcium channels present in photoreceptors, neurons, and hair cells; they interact simultaneously with specific calcium channel subunits, and active zone proteins, RIM1 and RIM2. RIMs are part of the matrix at the presynaptic active zone and are associated with synaptic vesicles through their interaction with the small GTPase Rab3. RIM-BPs play a role in regulating synaptic transmission by serving as adaptors and linking calcium channels with the synaptic vesicle release machinery. RIM-BPs contain three SH3 domains and two to three fibronectin III repeats. Invertebrates contain one, while vertebrates contain at least two RIM-BPs, RIM-BP1 and RIM-BP2. RIM-BP1 is also called peripheral-type benzodiazapine receptor associated protein 1 (PRAX-1). Mammals contain a third protein, RIM-BP3. RIM-BP1 and RIM-BP2 are predominantly expressed in the brain where they display overlapping but distinct expression patterns, while RIM-BP3 is almost exclusively expressed in the testis and is essential in spermiogenesis. The SH3 domains of RIM-BPs bind to the PxxP motifs of RIM1, RIM2, and L-type (alpha1D) and N-type (alpha1B) calcium channel subunits. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212946 Cd Length: 61 Bit Score: 45.45 E-value: 4.84e-06

                           10        20        30        40        50        60
                   ....*....|....*....|....*....|....*....|....*....|....*....|
gi 1804876928 1152 QVIAMYDYVAN----NED---ELNFSKGQLINVLNKDDPD-WWQGEINGVTGLFPSNYVK 1203
Cdd:cd12013      1 RMVALFDYDPResspNVDaevELSFRAGDIITVFGEMDEDgFYYGELNGQRGLVPSNFLE 60

Src homology 3 domain of ArfGAP with SH3 domain, ankyrin repeat and PH domain containing protein 1; ASAP1 is also called DDEF1 (Development and Differentiation Enhancing Factor 1), AMAP1, centaurin beta-4, or PAG2. an Arf GTPase activating protein (GAP) with activity towards Arf1 and Arf5 but not Arf6. However, it has been shown to bind GTP-Arf6 stably without GAP activity. It has been implicated in cell growth, migration, and survival, as well as in tumor invasion and malignancy. It binds paxillin and cortactin, two components of invadopodia which are essential for tumor invasiveness. It also binds focal adhesion kinase (FAK) and the SH2/SH3 adaptor CrkL. ASAP1 contains an N-terminal BAR domain, followed by a Pleckstrin homology (PH) domain, an Arf GAP domain, ankyrin (ANK) repeats, and a C-terminal SH3 domain. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212898 [Multi-domain] Cd Length: 57 Bit Score: 45.38 E-value: 4.91e-06

                           10        20        30        40
                   ....*....|....*....|....*....|....*....|
gi 1804876928 1020 DLTFIEGEEILVT-QKDGEWWTGSIG---DRTGIFPSNYV 1055
Cdd:cd11965     15 ELTFVEGEVIIVTgEEDQEWWIGHIEgqpERKGVFPVSFV 54

C-terminal Src homology 3 domain of GRB2-related adaptor protein 2; GRAP2 is also called GADS (GRB2-related adapter downstream of Shc), GrpL, GRB2L, Mona, or GRID (Grb2-related protein with insert domain). It is expressed specifically in the hematopoietic system. It plays an important role in T cell receptor (TCR) signaling by promoting the formation of the SLP-76:LAT complex, which couples the TCR to the Ras pathway. It also has roles in antigen-receptor and tyrosine kinase mediated signaling. GRAP2 is unique from other GRB2-like adaptor proteins in that it can be regulated by caspase cleavage. It contains an N-terminal SH3 domain, a central SH2 domain, and a C-terminal SH3 domain. The C-terminal SH3 domain of GRAP2 binds to different motifs found in substrate peptides including the typical PxxP motif in hematopoietic progenitor kinase 1 (HPK1), the RxxK motif in SLP-76 and HPK1, and the RxxxxK motif in phosphatase-like protein HD-PTP. SH3 domains are protein interaction domains that typically bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212883 [Multi-domain] Cd Length: 53 Bit Score: 45.20 E-value: 4.93e-06

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|.
gi 1804876928  924 AQALCSWTAKKDNHLNFSKHDIITVLEQQE-NWWFGEVHGGRGWFPKSYVK 973
Cdd:cd11950      2 VRALYDFEALEDDELGFNSGDVIEVLDSSNpSWWKGRLHGKLGLFPANYVA 52

Src homology 3 domain of Cortactin and related proteins; This subfamily includes cortactin, Abp1 (actin-binding protein 1), hematopoietic lineage cell-specific protein 1 (HS1), and similar proteins. These proteins are involved in regulating actin dynamics through direct or indirect interaction with the Arp2/3 complex, which is required to initiate actin polymerization. They all contain at least one C-terminal SH3 domain. Cortactin and HS1 bind Arp2/3 and actin through an N-terminal region that contains an acidic domain and several copies of a repeat domain found in cortactin and HS1. Abp1 binds actin via an N-terminal actin-depolymerizing factor (ADF) homology domain. Yeast Abp1 binds Arp2/3 directly through two acidic domains. Mammalian Abp1 does not directly interact with Arp2/3; instead, it regulates actin dynamics indirectly by interacting with dynamin and WASP family proteins. The C-terminal region of these proteins acts as an adaptor or scaffold that can connect membrane trafficking and signaling proteins that bind the SH3 domain within the actin network. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212753 [Multi-domain] Cd Length: 54 Bit Score: 45.38 E-value: 4.94e-06

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|.
gi 1804876928 1085 YVASGSEQLSLAPGQLILILKKNSSGWWQGElqarGKKRQKGWFPASHVKL 1135
Cdd:cd11819      8 YQAAEDNEISFVEGDIITQIEQIDEGWWLGV----NAKGQKGLFPANYVEL 54

Family of unknown function (DUF5401); This is a family of unknown function found in Chromadorea.

Pssm-ID: 375164 [Multi-domain] Cd Length: 722 Bit Score: 51.66 E-value: 4.97e-06

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1804876928  402 KRKANYERGNVELEKRRQALMEQQQREAERKAQK------EKEEWERKQRELQEQEWKKQLELEK-RLEKQRELERQREE 474
Cdd:pfam17380  386 ERQQKNERVRQELEAARKVKILEEERQRKIQQQKvemeqiRAEQEEARQREVRRLEEERAREMERvRLEEQERQQQVERL 465

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1804876928  475 ERRKEIERREAAKQELERQRRLEWERIRRQELLNQRNREQEEIVRLNSKKKSLHLELEalngKHQQISGRLQDVRLRKQT 554
Cdd:pfam17380  466 RQQEEERKRKKLELEKEKRDRKRAEEQRRKILEKELEERKQAMIEEERKRKLLEKEME----ERQKAIYEEERRREAEEE 541

                          170       180       190       200       210
                   ....*....|....*....|....*....|....*....|....*....|..
gi 1804876928  555 QKTEIevldkqcdlEIMEIKQLQQELQ---DYQNKLIYLVPEKQLLNERIKN 603
Cdd:pfam17380  542 RRKQQ---------EMEERRRIQEQMRkatEERSRLEAMEREREMMRQIVES 584

Src Homology 3 domain of SH3 domain-containing protein 21 (SH3D21) and similar proteins; N-terminal SH3 domain of the uncharacterized protein SH3 domain-containing protein 21, and similar uncharacterized domains, it belongs to the CD2AP-like_3 subfamily of proteins. The CD2AP-like_3 subfamily is composed of the third SH3 domain (SH3C) of CD2AP, CIN85 (Cbl-interacting protein of 85 kDa), and similar domains. CD2AP and CIN85 are adaptor proteins that bind to protein partners and assemble complexes that have been implicated in T cell activation, kidney function, and apoptosis of neuronal cells. They also associate with endocytic proteins, actin cytoskeleton components, and other adaptor proteins involved in receptor tyrosine kinase (RTK) signaling. CD2AP and the main isoform of CIN85 contain three SH3 domains, a proline-rich region, and a C-terminal coiled-coil domain. All of these domains enable CD2AP and CIN85 to bind various protein partners and assemble complexes that have been implicated in many different functions. SH3C of both proteins have been shown to bind to ubiquitin. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 213018 [Multi-domain] Cd Length: 55 Bit Score: 45.15 E-value: 5.03e-06

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|.
gi 1804876928 1010 LYSYSSVEPGDLTFIEGEEILVTQKDGE---WWTGSIGDRTGIFPSNYVKP 1057
Cdd:cd12142      5 LFDYNPVAPDELALKKGDVIEVISKETEdegWWEGELNGRRGFFPDNFVMP 55

N-terminal Src homology 3 domain of GRB2-related adaptor protein; GRAP is a GRB-2 like adaptor protein that is highly expressed in lymphoid tissues. It acts as a negative regulator of T cell receptor (TCR)-induced lymphocyte proliferation by downregulating the signaling to the Ras/ERK pathway. It has been identified as a regulator of TGFbeta signaling in diabetic kidney tubules and may have a role in the pathogenesis of the disease. GRAP contains an N-terminal SH3 domain, a central SH2 domain, and a C-terminal SH3 domain. The N-terminal SH3 domain of the related protein GRB2 binds to Sos and Sos-derived proline-rich peptides. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212881 [Multi-domain] Cd Length: 54 Bit Score: 45.19 E-value: 5.40e-06

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|.
gi 1804876928  787 ALYRFEARSHDEMSFNSGDIIQVDEKTiGEPGWLYGSFQGNFGWFPCNYVE 837
Cdd:cd11948      4 ALYSFQATESDELPFQKGDILKILNME-DDQNWYKAELQGREGYIPKNYIK 53

Src Homology 3 domain of Tec-like Protein Tyrosine Kinases; The Tec (Tyrosine kinase expressed in hepatocellular carcinoma) subfamily is composed of Tec, Btk, Bmx (Etk), Itk (Tsk, Emt), Rlk (Txk), and similar proteins. They are cytoplasmic (or nonreceptor) tyr kinases containing Src homology protein interaction domains (SH3, SH2) N-terminal to the catalytic tyr kinase domain. Most Tec subfamily members (except Rlk) also contain an N-terminal pleckstrin homology (PH) domain, which binds the products of PI3K and allows membrane recruitment and activation. In addition, some members contain the Tec homology (TH) domain, which contains proline-rich and zinc-binding regions. Tec kinases are expressed mainly by haematopoietic cells, although Tec and Bmx are also found in endothelial cells. B-cells express Btk and Tec, while T-cells express Itk, Txk, and Tec. Collectively, Tec kinases are expressed in a variety of myeloid cells such as mast cells, platelets, macrophages, and dendritic cells. Each Tec kinase shows a distinct cell-type pattern of expression. The function of Tec kinases in lymphoid cells have been studied extensively. They play important roles in the development, differentiation, maturation, regulation, survival, and function of B-cells and T-cells. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212702 [Multi-domain] Cd Length: 54 Bit Score: 44.96 E-value: 5.65e-06

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|..
gi 1804876928 1008 IALYSYSSVEPGDLTFIEGEEILVTQKDGE-WWTGSIGD-RTGIFPSNYVKP 1057
Cdd:cd11768      3 VALYDFQPIEPGDLPLEKGEEYVVLDDSNEhWWRARDKNgNEGYIPSNYVTE 54

First Src Homology 3 domain of Sorbin and SH3 domain containing 1 (Sorbs1), also called ponsin; Sorbs1 is also called ponsin, SH3P12, or CAP (c-Cbl associated protein). It is an adaptor protein containing one sorbin homology (SoHo) and three SH3 domains. It binds Cbl and plays a major role in regulating the insulin signaling pathway by enhancing insulin-induced phosphorylation of Cbl. Sorbs1, like vinexin, localizes at cell-ECM and cell-cell adhesion sites where it binds vinculin, paxillin, and afadin. It may function in the control of cell motility. Other interaction partners of Sorbs1 include c-Abl, Sos, flotillin, Grb4, ataxin-7, filamin C, among others. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212852 [Multi-domain] Cd Length: 55 Bit Score: 44.95 E-value: 5.97e-06

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|...
gi 1804876928 1152 QVIAMYDYVANNEDELNFSKGQLINVLNKDDPDWWQGEINGVTGLFPSNYVKM 1204
Cdd:cd11919      2 PARAKFDFKAQTLKELPLQKGDIVYIYKQIDQNWYEGEHHGRVGIFPRSYIEL 54

First Src Homology 3 domain (SH3A) of CD2-associated protein and similar proteins; This subfamily is composed of the first SH3 domain (SH3A) of CD2AP, CIN85 (Cbl-interacting protein of 85 kDa), and similar domains. CD2AP and CIN85 are adaptor proteins that bind to protein partners and assemble complexes that have been implicated in T cell activation, kidney function, and apoptosis of neuronal cells. They also associate with endocytic proteins, actin cytoskeleton components, and other adaptor proteins involved in receptor tyrosine kinase (RTK) signaling. CD2AP and the main isoform of CIN85 contain three SH3 domains, a proline-rich region, and a C-terminal coiled-coil domain. All of these domains enable CD2AP and CIN85 to bind various protein partners and assemble complexes that have been implicated in many different functions. SH3A of both proteins bind to an atypical PXXXPR motif at the C-terminus of Cbl and the cytoplasmic domain of the cell adhesion protein CD2. CIN85 SH3A binds to internal proline-rich motifs within the proline-rich region; this intramolecular interaction serves as a regulatory mechanism to keep CIN85 in a closed conformation, preventing the recruitment of other proteins. CIN85 SH3A has also been shown to bind ubiquitin. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212806 [Multi-domain] Cd Length: 53 Bit Score: 44.95 E-value: 6.41e-06

                           10        20        30        40
                   ....*....|....*....|....*....|....*....|....*.
gi 1804876928  930 WTAKKDNHLNFSKHDIIT-VLEQQENWWFGEVHGGRGWFPKSYVKI 974
Cdd:cd11873      8 YDAEEPDELTLKVGDIITnVKKMEEGWWEGTLNGKRGMFPDNFVKV 53

Second or C-terminal Src homology 3 domain of NADPH oxidase (Nox) Organizing protein 1; Nox Organizing protein 1 (NoxO1) is a critical regulator of enzyme kinetics of the nonphagocytic NADPH oxidase Nox1, which catalyzes the transfer of electrons from NADPH to molecular oxygen to form superoxide. Nox1 is expressed in colon, stomach, uterus, prostate, and vascular smooth muscle cells. NoxO1 is involved in targeting activator subunits (such as NoxA1) to Nox1. It is co-localized with Nox1 in the membranes of resting cells and directs the subcellular localization of Nox1. NoxO1 contains an N-terminal Phox homology (PX) domain, tandem SH3 domains (N-SH3 and C-SH3), and a C-terminal proline-rich region (PRR). This model characterizes the second SH3 domain (or C-SH3) of NoxO1. The tandem SH3 domains of NoxO1 interact with the PRR of p22phox, which also complexes with Nox1. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212957 Cd Length: 53 Bit Score: 45.02 E-value: 6.54e-06

                           10        20        30        40
                   ....*....|....*....|....*....|....*....|....*....
gi 1804876928 1155 AMYDYVANNEDELNFSKGQLINVLNKDDPDWWQGEINGVTGLFPSNYVK 1203
Cdd:cd12024      4 ATRAYEAQKEDELSVPAGVVVEVLQKSDNGWWLIRYNGRAGYVPSMYLQ 52

Second Src Homology 3 domain of Sorbin and SH3 domain containing (Sorbs) proteins and similar domains; This family, also called the vinexin family, is composed predominantly of adaptor proteins containing one sorbin homology (SoHo) and three SH3 domains. Members include the second SH3 domains of Sorbs1 (or ponsin), Sorbs2 (or ArgBP2), Vinexin (or Sorbs3), and similar domains. They are involved in the regulation of cytoskeletal organization, cell adhesion, and growth factor signaling. Members of this family bind multiple partners including signaling molecules like c-Abl, c-Arg, Sos, and c-Cbl, as well as cytoskeletal molecules such as vinculin and afadin. They may have overlapping functions. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212716 [Multi-domain] Cd Length: 53 Bit Score: 45.03 E-value: 6.55e-06

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....*.
gi 1804876928  786 KALYRFEARSHDEMSFNSGDII----QVDEKtigepgWLYGSFQGNFGWFPCNYVE 837
Cdd:cd11782      3 RAKYNFNADTGVELSFRKGDVItltrRVDEN------WYEGRIGGRQGIFPVSYVQ 52

Src Homology 3 domain of GTPase Regulator Associated with Focal adhesion kinase; GRAF, also called Rho GTPase activating protein 26 (ARHGAP26), Oligophrenin-1-like (OPHN1L) or GRAF1, is a GAP with activity towards RhoA and Cdc42 and is only weakly active towards Rac1. It influences Rho-mediated cytoskeletal rearrangements and binds focal adhesion kinase (FAK), which is a critical component of integrin signaling. It is essential for the major clathrin-independent endocytic pathway mediated by pleiomorphic membranes. GRAF contains an N-terminal BAR domain, followed by a Pleckstrin homology (PH) domain, a Rho GAP domain, and a C-terminal SH3 domain. The SH3 domain of GRAF binds PKNbeta, a target of the small GTPase Rho. SH3 domains bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs; they play a role in the regulation of enzymes by intramolecular interactions, changing the subcellular localization of signal pathway components and mediate multiprotein complex assemblies.

Pssm-ID: 212997 Cd Length: 56 Bit Score: 45.11 E-value: 6.72e-06

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|
gi 1804876928 1155 AMYDYVANNEDELNFSKGQLI-NVLNKDDPDWWQGEINGVTGLFPSNYVK 1203
Cdd:cd12064      5 ALYACKAEHDSELSFTAGTVFdNVHPSQEPGWLEGTLNGKTGLIPENYVE 54

exonuclease SbcC; All proteins in this family for which functions are known are part of an exonuclease complex with sbcD homologs. This complex is involved in the initiation of recombination to regulate the levels of palindromic sequences in DNA. This family is based on the phylogenomic analysis of JA Eisen (1999, Ph.D. Thesis, Stanford University). [DNA metabolism, DNA replication, recombination, and repair]

Pssm-ID: 129705 [Multi-domain] Cd Length: 1042 Bit Score: 51.12 E-value: 7.10e-06

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1804876928  371 KQIDSINGTLPSYQKIQEEEPQKKLPVTFEDKRKANYERGNVELEKRRQalMEQQQREAERKAQKEKEEWERKQRELQEQ 450
Cdd:TIGR00618  335 KQQSSIEEQRRLLQTLHSQEIHIRDAHEVATSIREISCQQHTLTQHIHT--LQQQKTTLTQKLQSLCKELDILQREQATI 412

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1804876928  451 EWKKQ---------LELEKRLEKQRELERQREEERRKEIERREAAKQELERQRRLEWERIRRQELLNQRNREQEEIVRLN 521
Cdd:TIGR00618  413 DTRTSafrdlqgqlAHAKKQQELQQRYAELCAAAITCTAQCEKLEKIHLQESAQSLKEREQQLQTKEQIHLQETRKKAVV 492

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1804876928  522 SKKKSLHLELEA--------LNGKHQQI------SGRLQDVRLRKQTQKTEIEVLDKQCDLEIMEIKQLQQELQDYQNKL 587
Cdd:TIGR00618  493 LARLLELQEEPCplcgscihPNPARQDIdnpgplTRRMQRGEQTYAQLETSEEDVYHQLTSERKQRASLKEQMQEIQQSF 572

                          250       260       270       280       290       300       310       320
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1804876928  588 IYLVPEKQLLNERIKNMQlgntpdlgidllhkkslekeELCQRLKEQLDALEKETASKLSEMDSfnnqlkcgnmddsvlq 667
Cdd:TIGR00618  573 SILTQCDNRSKEDIPNLQ--------------------NITVRLQDLTEKLSEAEDMLACEQHA---------------- 616

                          330       340       350       360       370       380       390       400
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1804876928  668 cllsllsclnnlflLLKELRESYNTQQLALEQLHKIKRDKLKEIERKRSELIQKKKLEDEAIRKAKQGKENLWRESLRKE 747
Cdd:TIGR00618  617 --------------LLRKLQPEQDLQDVRLHLQQCSQELALKLTALHALQLTLTQERVREHALSIRVLPKELLASRQLAL 682

                          410       420       430
                   ....*....|....*....|....*....|...
gi 1804876928  748 EEEKQKRLQE-------EKTQEKVQEEERKVEE 773
Cdd:TIGR00618  683 QKMQSEKEQLtywkemlAQCQTLLRELETHIEE 715

C-terminal Src Homology 3 domain of the Nebulin family of proteins; Nebulin family proteins contain multiple nebulin repeats, and may contain an N-terminal LIM domain and/or a C-terminal SH3 domain. They have molecular weights ranging from 34 to 900 kD, depending on the number of nebulin repeats, and they all bind actin. They are involved in the regulation of actin filament architecture and function as stabilizers and scaffolds for cytoskeletal structures with which they associate, such as long actin filaments or focal adhesions. Nebulin family proteins that contain a C-terminal SH3 domain include the giant filamentous protein nebulin, nebulette, Lasp1, and Lasp2. Lasp2, also called LIM-nebulette, is an alternatively spliced variant of nebulette. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212723 [Multi-domain] Cd Length: 55 Bit Score: 44.62 E-value: 7.55e-06

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....*
gi 1804876928 1007 YIALYSYSSVEPGDLTFIEGEEIL-VTQKDGEWWTGSIgDRT---GIFPSNYVKP 1057
Cdd:cd11789      2 YRAMYDYAAADDDEVSFQEGDVIInVEIIDDGWMEGTV-QRTgqsGMLPANYVEL 55

First Src Homology 3 domain (SH3A) of CD2-associated protein and similar proteins; This subfamily is composed of the first SH3 domain (SH3A) of CD2AP, CIN85 (Cbl-interacting protein of 85 kDa), and similar domains. CD2AP and CIN85 are adaptor proteins that bind to protein partners and assemble complexes that have been implicated in T cell activation, kidney function, and apoptosis of neuronal cells. They also associate with endocytic proteins, actin cytoskeleton components, and other adaptor proteins involved in receptor tyrosine kinase (RTK) signaling. CD2AP and the main isoform of CIN85 contain three SH3 domains, a proline-rich region, and a C-terminal coiled-coil domain. All of these domains enable CD2AP and CIN85 to bind various protein partners and assemble complexes that have been implicated in many different functions. SH3A of both proteins bind to an atypical PXXXPR motif at the C-terminus of Cbl and the cytoplasmic domain of the cell adhesion protein CD2. CIN85 SH3A binds to internal proline-rich motifs within the proline-rich region; this intramolecular interaction serves as a regulatory mechanism to keep CIN85 in a closed conformation, preventing the recruitment of other proteins. CIN85 SH3A has also been shown to bind ubiquitin. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212806 [Multi-domain] Cd Length: 53 Bit Score: 44.56 E-value: 7.58e-06

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....
gi 1804876928  785 YKALYRFEARSHDEMSFNSGDIIQVDEKTigEPGWLYGSFQGNFGWFPCNYVEK 838
Cdd:cd11873      2 VIVEFDYDAEEPDELTLKVGDIITNVKKM--EEGWWEGTLNGKRGMFPDNFVKV 53

Fifth Src homology 3 domain (or SH3E) of Intersectin-2; Intersectin-2 (ITSN2) is an adaptor protein that functions in exo- and endocytosis, actin cytoskeletal reorganization, and signal transduction. It plays a role in clathrin-coated pit (CCP) formation. It binds to many proteins through its multidomain structure and facilitate the assembly of multimeric complexes. ITSN2 also functions as a specific GEF for Cdc42 activation in epithelial morphogenesis, and is required in mitotic spindle orientation. It exists in alternatively spliced short and long isoforms. The short isoform contains two Eps15 homology domains (EH1 and EH2), a coiled-coil region and five SH3 domains (SH3A-E), while the long isoform, in addition, contains RhoGEF (also called Dbl-homologous or DH), Pleckstrin homology (PH) and C2 domains. The fifth SH3 domain (or SH3E) of ITSN2 is expected to bind protein partners, similar to ITSN1 which has been shown to bind many protein partners including SGIP1, Sos1, dynamin1/2, CIN85, c-Cbl, SHIP2, N-WASP, and synaptojanin-1, among others. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212929 [Multi-domain] Cd Length: 54 Bit Score: 44.97 E-value: 7.64e-06

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|.
gi 1804876928  787 ALYRFEARSHDEMSFNSGDIIQVDEKTigEPGWLYGSFQGNFGWFPCNYVE 837
Cdd:cd11996      5 AMYDYTANNEDELSFSKGQLINVLNKD--DPDWWQGEINGVTGLFPSNYVK 53

First Src Homology 3 domain of Nck adaptor proteins; Nck adaptor proteins regulate actin cytoskeleton dynamics by linking proline-rich effector molecules to protein tyrosine kinases and phosphorylated signaling intermediates. They contain three SH3 domains and a C-terminal SH2 domain. They function downstream of the PDGFbeta receptor and are involved in Rho GTPase signaling and actin dynamics. Vertebrates contain two Nck adaptor proteins: Nck1 (also called Nckalpha) and Nck2 (also called Nckbeta or Growth factor receptor-bound protein 4, Grb4), which show partly overlapping functions but also bind distinct targets. Their SH3 domains are involved in recruiting downstream effector molecules, such as the N-WASP/Arp2/3 complex, which when activated induces actin polymerization that results in the production of pedestals, or protrusions of the plasma membrane. The first SH3 domain of Nck proteins preferentially binds the PxxDY sequence, which is present in the CD3e cytoplasmic tail. This binding inhibits phosphorylation by Src kinases, resulting in the downregulation of TCR surface expression. SH3 domains are protein interaction domains that usually bind to proline-rich ligands with moderate affinity and selectivity, preferentially a PxxP motif. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212699 [Multi-domain] Cd Length: 51 Bit Score: 44.72 E-value: 7.81e-06

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|.
gi 1804876928 1153 VIAMYDYVANNEDELNFSKGQLINVLNkDDPDWWQGE-INGVTGLFPSNYV 1202
Cdd:cd11765      2 VVAKYDYTAQGDQELSIKKNEKLTLLD-DSKHWWKVQnSSNQTGYVPSNYV 51

Src homology 3 domain of APC-Stimulated guanine nucleotide Exchange Factor; ASEF, also called ARHGEF4, exists in an autoinhibited form and is activated upon binding of the tumor suppressor APC (adenomatous polyposis coli). GEFs activate small GTPases by exchanging bound GDP for free GTP. ASEF can activate Rac1 or Cdc42. Truncated ASEF, which is found in colorectal cancers, is constitutively active and has been shown to promote angiogenesis and cancer cell migration. ASEF contains a SH3 domain followed by RhoGEF (also called Dbl-homologous or DH) and Pleckstrin Homology (PH) domains. In its autoinhibited form, the SH3 domain of ASEF forms an extensive interface with the DH and PH domains, blocking the Rac binding site. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212906 [Multi-domain] Cd Length: 73 Bit Score: 45.39 E-value: 7.81e-06

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|
gi 1804876928 1155 AMYDYVANNEDELNFSKGQLINVLNKDDPDWWQGEINGVTGLFPSNYVKM 1204
Cdd:cd11973     22 ALWDHVTMDDQELGFKAGDVIEVMDATNKEWWWGRVLDSEGWFPASFVRL 71

Src Homology 3 domain of GTPase Regulator Associated with Focal adhesion kinase 3; GRAF3 is also called Rho GTPase activating protein 42 (ARHGAP42) or ARHGAP10-like. Though its function has not been characterized, it may be a GAP with activity towards RhoA and Cdc42, based on its similarity to GRAF and GRAF2. It contains an N-terminal BAR domain, followed by a Pleckstrin homology (PH) domain, a Rho GAP domain, and a C-terminal SH3 domain. The SH3 domain of GRAF and GRAF2 binds PKNbeta, a target of the small GTPase Rho. SH3 domains bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs; they play a role in the regulation of enzymes by intramolecular interactions, changing the subcellular localization of signal pathway components and mediate multiprotein complex assemblies.

Pssm-ID: 212999 Cd Length: 55 Bit Score: 44.67 E-value: 7.86e-06

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|..
gi 1804876928 1152 QVIAMYDYVANNEDELNFSKGQLI-NVLNKDDPDWWQGEINGVTGLFPSNYV 1202
Cdd:cd12066      1 QAKAMYSCKAEHSHELSFPQGAIFsNVYPSVEPGWLKATYEGKTGLVPENYV 52

Src Homology 3 domain of Tec (Tyrosine kinase expressed in hepatocellular carcinoma); Tec is a cytoplasmic (or nonreceptor) tyr kinase containing Src homology protein interaction domains (SH3, SH2) N-terminal to the catalytic tyr kinase domain. It also contains an N-terminal pleckstrin homology (PH) domain, which binds the products of PI3K and allows membrane recruitment and activation, and the Tec homology (TH) domain, which contains proline-rich and zinc-binding regions. It is more widely-expressed than other Tec subfamily kinases. Tec is found in endothelial cells, both B- and T-cells, and a variety of myeloid cells including mast cells, erythroid cells, platelets, macrophages and neutrophils. Tec is a key component of T-cell receptor (TCR) signaling, and is important in TCR-stimulated proliferation, IL-2 production and phospholipase C-gamma1 activation. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212838 [Multi-domain] Cd Length: 56 Bit Score: 44.81 E-value: 7.87e-06

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|.
gi 1804876928 1153 VIAMYDYVANNEDELNFSKGQLINVLNKDDPDWWQG-EINGVTGLFPSNYV 1202
Cdd:cd11905      3 VVAMYDFQPTEPHDLRLETGEEYVILEKNDVHWWKArDKYGKEGYIPSNYV 53

Src Homology 3 domain of GTPase Regulator Associated with Focal adhesion kinase 3; GRAF3 is also called Rho GTPase activating protein 42 (ARHGAP42) or ARHGAP10-like. Though its function has not been characterized, it may be a GAP with activity towards RhoA and Cdc42, based on its similarity to GRAF and GRAF2. It contains an N-terminal BAR domain, followed by a Pleckstrin homology (PH) domain, a Rho GAP domain, and a C-terminal SH3 domain. The SH3 domain of GRAF and GRAF2 binds PKNbeta, a target of the small GTPase Rho. SH3 domains bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs; they play a role in the regulation of enzymes by intramolecular interactions, changing the subcellular localization of signal pathway components and mediate multiprotein complex assemblies.

Pssm-ID: 212999 Cd Length: 55 Bit Score: 44.67 E-value: 7.94e-06

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|..
gi 1804876928  786 KALYRFEARSHDEMSFNSGDIIQVDEKTIgEPGWLYGSFQGNFGWFPCNYVE 837
Cdd:cd12066      3 KAMYSCKAEHSHELSFPQGAIFSNVYPSV-EPGWLKATYEGKTGLVPENYVV 53

Third Src homology 3 domain of ADAM-binding protein Eve-1; Eve-1, also called SH3 domain-containing protein 19 (SH3D19) or EEN-binding protein (EBP), exists in multiple alternatively spliced isoforms. The longest isoform contains five SH3 domain in the C-terminal region and seven proline-rich motifs in the N-terminal region. It is abundantly expressed in skeletal muscle and heart, and may be involved in regulating the activity of ADAMs (A disintegrin and metalloproteases). Eve-1 interacts with EEN, an endophilin involved in endocytosis and may be the target of the MLL-EEN fusion protein that is implicated in leukemogenesis. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212750 [Multi-domain] Cd Length: 51 Bit Score: 44.71 E-value: 7.95e-06

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|.
gi 1804876928  786 KALYRFEARSHDEMSFNSGDIIQVDEKtIGEPgWLYGSFQGNFGWFPCNYV 836
Cdd:cd11816      3 VARFDFEGEQEDELSFSEGDVITLKEY-VGEE-WAKGELNGKIGIFPLNFV 51

Second or C-terminal Src homology 3 domain of the p47phox subunit of NADPH oxidase, also called Neutrophil Cytosolic Factor 1; p47phox, or NCF1, is a cytosolic subunit of the phagocytic NADPH oxidase complex (also called Nox2 or gp91phox), which plays a key role in the ability of phagocytes to defend against bacterial infections. NADPH oxidase catalyzes the transfer of electrons from NADPH to oxygen during phagocytosis forming superoxide and reactive oxygen species. p47phox is required for activation of NADH oxidase and plays a role in translocation. It contains an N-terminal Phox homology (PX) domain, tandem SH3 domains (N-SH3 and C-SH3), a polybasic/autoinhibitory region, and a C-terminal proline-rich region (PRR). This model characterizes the second SH3 domain (or C-SH3) of p47phox. In its inactive state, the tandem SH3 domains interact intramolecularly with the autoinhibitory region; upon activation, the tandem SH3 domains are exposed through a conformational change, resulting in their binding to the PRR of p22phox and the activation of NADPH oxidase. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212955 [Multi-domain] Cd Length: 53 Bit Score: 44.83 E-value: 8.14e-06

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|..
gi 1804876928 1007 YIALYSYSSVEPGDLTFIEGEEILVTQK--DGeWWTGSIGDRTGIFPSNYVK 1056
Cdd:cd12022      2 YITIKAYTAVEEDELTLLEGEAIEVIHKllDG-WWVVRKGEVTGYFPSMYLQ 52

Third (or C-terminal) Src Homology 3 domain of Vinexin, also called Sorbin and SH3 domain containing 3 (Sorbs3); Vinexin is also called Sorbs3, SH3P3, and SH3-containing adapter molecule 1 (SCAM-1). It is an adaptor protein containing one sorbin homology (SoHo) and three SH3 domains. Vinexin was first identified as a vinculin binding protein; it is co-localized with vinculin at cell-ECM and cell-cell adhesion sites. There are several splice variants of vinexin: alpha, which contains the SoHo and three SH3 domains and displays tissue-specific expression; and beta, which contains only the three SH3 domains and is widely expressed. Vinexin alpha stimulates the accumulation of F-actin at focal contact sites. Vinexin also promotes keratinocyte migration and wound healing. The SH3 domains of vinexin have been reported to bind a number of ligands including vinculin, WAVE2, DLG5, Abl, and Cbl. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212851 [Multi-domain] Cd Length: 58 Bit Score: 44.56 E-value: 8.87e-06

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|
gi 1804876928 1155 AMYDYVANNEDELNFSKGQLINVLNKDDPDWWQG--EINGVTGLFPSNYV 1202
Cdd:cd11918      6 AVYQYRPQNEDELELREGDRVDVMQQCDDGWFVGvsRRTQKFGTFPGNYV 55

First Src Homology 3 domain (SH3A) of Cbl-interacting protein of 85 kDa; CIN85, also called SH3 domain-containing kinase-binding protein 1 (SH3KBP1) or CD2-binding protein 3 (CD2BP3) or Ruk, is an adaptor protein that is involved in the downregulation of receptor tyrosine kinases by facilitating endocytosis through interaction with endophilin-associated ubiquitin ligase Cbl proteins. It is also important in many other cellular processes including vesicle-mediated transport, cytoskeletal remodelling, apoptosis, cell adhesion and migration, and viral infection, among others. CIN85 exists as multiple variants from alternative splicing; the main variant contains three SH3 domains, a proline-rich region, and a C-terminal coiled-coil domain. All of these domains enable CIN85 to bind various protein partners and assemble complexes that have been implicated in many different functions. This alignment model represents the first SH3 domain (SH3A) of CIN85; SH3A binds to internal proline-rich motifs within the proline-rich region. This intramolecular interaction serves as a regulatory mechanism to keep CIN85 in a closed conformation, preventing the recruitment of other proteins. SH3A has also been shown to bind ubiquitin and to an atypical PXXXPR motif at the C-terminus of Cbl and the cytoplasmic end of the cell adhesion protein CD2. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212985 [Multi-domain] Cd Length: 53 Bit Score: 44.50 E-value: 9.17e-06

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|..
gi 1804876928 1006 EYIALYSYSSVEPGDLTFIEGEEIL-VTQKDGEWWTGSIGDRTGIFPSNYVK 1056
Cdd:cd12052      1 EAIVEFDYKAQHEDELTITVGDIITkIKKDDGGWWEGEIKGRRGLFPDNFVR 52

Second Src Homology 3 domain of Nck1 adaptor protein; Nck1 (also called Nckalpha) plays a crucial role in connecting signaling pathways of tyrosine kinase receptors and important effectors in actin dynamics and cytoskeletal remodeling. It binds and activates RasGAP, resulting in the downregulation of Ras. It is also involved in the signaling of endothilin-mediated inhibition of cell migration. Nck adaptor proteins regulate actin cytoskeleton dynamics by linking proline-rich effector molecules to protein tyrosine kinases and phosphorylated signaling intermediates. They contain three SH3 domains and a C-terminal SH2 domain. They function downstream of the PDGFbeta receptor and are involved in Rho GTPase signaling and actin dynamics. Vertebrates contain two Nck adaptor proteins: Nck1 (also called Nckalpha) and Nck2, which show partly overlapping functions but also bind distinct targets. The second SH3 domain of Nck appears to prefer ligands containing the APxxPxR motif. SH3 domains are protein interaction domains that usually bind to proline-rich ligands with moderate affinity and selectivity, preferentially a PxxP motif. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212834 [Multi-domain] Cd Length: 55 Bit Score: 44.64 E-value: 9.20e-06

                           10        20        30        40
                   ....*....|....*....|....*....|....*....|....*..
gi 1804876928 1011 YSYSSVEPGDLTFIEGEEILVTQK--DGeWWTGSIGDRTGIFPSNYV 1055
Cdd:cd11901      8 FNYTAEREDELSLVKGTKVIVMEKcsDG-WWRGSYNGQVGWFPSNYV 53

Src Homology 3 domain of Brain-specific Angiogenesis Inhibitor 1-Associated Protein 2-Like 2; BAIAP2L2 co-localizes with clathrin plaques but its function has not been determined. It contains an N-terminal IMD or Inverse-Bin/Amphiphysin/Rvs (I-BAR) domain, an SH3 domain, and a WASP homology 2 (WH2) actin-binding motif at the C-terminus. The related proteins, BAIAP2L1 and IRSp53, function as regulators of membrane dynamics and the actin cytoskeleton. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212847 [Multi-domain] Cd Length: 59 Bit Score: 44.81 E-value: 9.21e-06

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....*
gi 1804876928  925 QALCSWTAKKdNH--LNFSKHDIITVL--EQQENWWFGEVHGG--RGWFPKSYVK 973
Cdd:cd11914      4 RAIVSHPAGS-NPtlLRFNRGDIITVLvpEARNGWLYGKLEGSsrQGWFPEAYVK 57

Second Src Homology 3 domain (SH3B) of CD2-associated protein and similar proteins; This subfamily is composed of the second SH3 domain (SH3B) of CD2AP, CIN85 (Cbl-interacting protein of 85 kDa), and similar domains. CD2AP and CIN85 are adaptor proteins that bind to protein partners and assemble complexes that have been implicated in T cell activation, kidney function, and apoptosis of neuronal cells. They also associate with endocytic proteins, actin cytoskeleton components, and other adaptor proteins involved in receptor tyrosine kinase (RTK) signaling. CD2AP and the main isoform of CIN85 contain three SH3 domains, a proline-rich region, and a C-terminal coiled-coil domain. All of these domains enable CD2AP and CIN85 to bind various protein partners and assemble complexes that have been implicated in many different functions. SH3B of both proteins have been shown to bind to Cbl. In the case of CD2AP, its SH3B binds to Cbl at a site distinct from the c-Cbl/SH3A binding site. The CIN85 SH3B also binds ubiquitin. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212807 [Multi-domain] Cd Length: 53 Bit Score: 44.63 E-value: 9.25e-06

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|..
gi 1804876928  786 KALYRFEARSHDEMSFNSGDIIQVDEKTigEPGWLYGSFQGNFGWFPCNYVE 837
Cdd:cd11874      3 KVLFSYTPQNEDELELKVGDTIEVLGEV--EEGWWEGKLNGKVGVFPSNFVK 52

Second Src Homology 3 domain of Sorbin and SH3 domain containing (Sorbs) proteins and similar domains; This family, also called the vinexin family, is composed predominantly of adaptor proteins containing one sorbin homology (SoHo) and three SH3 domains. Members include the second SH3 domains of Sorbs1 (or ponsin), Sorbs2 (or ArgBP2), Vinexin (or Sorbs3), and similar domains. They are involved in the regulation of cytoskeletal organization, cell adhesion, and growth factor signaling. Members of this family bind multiple partners including signaling molecules like c-Abl, c-Arg, Sos, and c-Cbl, as well as cytoskeletal molecules such as vinculin and afadin. They may have overlapping functions. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212716 [Multi-domain] Cd Length: 53 Bit Score: 44.65 E-value: 9.32e-06

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|...
gi 1804876928  923 KAQALCSWTAKKDNHLNFSKHDIITVLEQ-QENWWFGEVHGGRGWFPKSYVKI 974
Cdd:cd11782      1 EARAKYNFNADTGVELSFRKGDVITLTRRvDENWYEGRIGGRQGIFPVSYVQV 53

Src Homology 3 domain of eumetazoan Peroxisomal biogenesis factor 13; PEX13 is a peroxin and is required for protein import into the peroxisomal matrix and membrane. It is an integral membrane protein that is essential for the localization of PEX14 and the import of proteins containing the peroxisome matrix targeting signals, PTS1 and PTS2. Mutations of the PEX13 gene in humans lead to a wide range of peroxisome biogenesis disorders (PBDs), the most severe of which is known as Zellweger syndrome (ZS), a severe multisystem disorder characterized by hypotonia, psychomotor retardation, and neuronal migration defects. PEX13 contains two transmembrane regions and a C-terminal SH3 domain. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212798 Cd Length: 58 Bit Score: 44.54 E-value: 9.38e-06

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....*
gi 1804876928  786 KALYRFEARSHDEMSFNSGDIIQVDEKTIGE--PGWLYGSFQG-NFGWFPCNYVE 837
Cdd:cd11864      3 RAEYDFVAESEDELSFRAGDKLRLAPKELQPrvRGWLLATVDGqKIGLVPANYVK 57

Src Homology 3 domain of Abelson helper integration site-1 (AHI-1); AHI-1, also called Jouberin, is expressed in high levels in the brain, gonad tissues, and skeletal muscle. It is an adaptor protein that interacts with the small GTPase Rab8a and regulates it distribution and function, affecting cilium formation and vesicle transport. Mutations in the AHI-1 gene can cause Joubert syndrome, a disorder characterized by brainstem malformations, cerebellar aplasia/hypoplasia, and retinal dystrophy. AHI-1 variation is also associated with susceptibility to schizophrenia and type 2 diabetes mellitus progression. AHI-1 contains WD40 and SH3 domains. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212746 [Multi-domain] Cd Length: 52 Bit Score: 44.42 E-value: 9.51e-06

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|.
gi 1804876928  787 ALYRFEARSHDEMSFNSGDIIQVDEKTigEPGWLYGSF-QGNFGWFPCNYV 836
Cdd:cd11812      4 ALYDYTANRSDELTIHRGDIIRVLYKD--NDNWWFGSLvNGQQGYFPANYV 52

N-terminal Src homology 3 domain of GRB2-related adaptor protein; GRAP is a GRB-2 like adaptor protein that is highly expressed in lymphoid tissues. It acts as a negative regulator of T cell receptor (TCR)-induced lymphocyte proliferation by downregulating the signaling to the Ras/ERK pathway. It has been identified as a regulator of TGFbeta signaling in diabetic kidney tubules and may have a role in the pathogenesis of the disease. GRAP contains an N-terminal SH3 domain, a central SH2 domain, and a C-terminal SH3 domain. The N-terminal SH3 domain of the related protein GRB2 binds to Sos and Sos-derived proline-rich peptides. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212881 [Multi-domain] Cd Length: 54 Bit Score: 44.42 E-value: 1.00e-05

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....
gi 1804876928  923 KAQALCSWTAKKDNHLNFSKHDIITVL--EQQENWWFGEVHGGRGWFPKSYVKI 974
Cdd:cd11948      1 EAVALYSFQATESDELPFQKGDILKILnmEDDQNWYKAELQGREGYIPKNYIKV 54

Src homology 3 domain of Src Protein Tyrosine Kinase; Src (or c-Src) is a cytoplasmic (or non-receptor) PTK and is the vertebrate homolog of the oncogenic protein (v-Src) from Rous sarcoma virus. Together with other Src subfamily proteins, it is involved in signaling pathways that regulate cytokine and growth factor responses, cytoskeleton dynamics, cell proliferation, survival, and differentiation. Src also play a role in regulating cell adhesion, invasion, and motility in cancer cells, and tumor vasculature, contributing to cancer progression and metastasis. Elevated levels of Src kinase activity have been reported in a variety of human cancers. Several inhibitors of Src have been developed as anti-cancer drugs. Src is also implicated in acute inflammatory responses and osteoclast function. Src kinases contain an N-terminal SH4 domain with a myristoylation site, followed by SH3 and SH2 domains, a tyr kinase domain, and a regulatory C-terminal region containing a conserved tyr. They are activated by autophosphorylation at the tyr kinase domain, but are negatively regulated by phosphorylation at the C-terminal tyr by Csk (C-terminal Src Kinase). The SH3 domain of Src kinases contributes to substrate recruitment by binding adaptor proteins/substrates, and regulation of kinase activity through an intramolecular interaction. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212941 [Multi-domain] Cd Length: 56 Bit Score: 44.72 E-value: 1.02e-05

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....*
gi 1804876928 1007 YIALYSYSSVEPGDLTFIEGEEI-LVTQKDGEWWTG---SIGdRTGIFPSNYVKP 1057
Cdd:cd12008      2 FVALYDYESRTETDLSFKKGERLqIVNNTEGDWWLAhslTTG-QTGYIPSNYVAP 55

Second Src Homology 3 domain of Nck1 adaptor protein; Nck1 (also called Nckalpha) plays a crucial role in connecting signaling pathways of tyrosine kinase receptors and important effectors in actin dynamics and cytoskeletal remodeling. It binds and activates RasGAP, resulting in the downregulation of Ras. It is also involved in the signaling of endothilin-mediated inhibition of cell migration. Nck adaptor proteins regulate actin cytoskeleton dynamics by linking proline-rich effector molecules to protein tyrosine kinases and phosphorylated signaling intermediates. They contain three SH3 domains and a C-terminal SH2 domain. They function downstream of the PDGFbeta receptor and are involved in Rho GTPase signaling and actin dynamics. Vertebrates contain two Nck adaptor proteins: Nck1 (also called Nckalpha) and Nck2, which show partly overlapping functions but also bind distinct targets. The second SH3 domain of Nck appears to prefer ligands containing the APxxPxR motif. SH3 domains are protein interaction domains that usually bind to proline-rich ligands with moderate affinity and selectivity, preferentially a PxxP motif. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212834 [Multi-domain] Cd Length: 55 Bit Score: 44.64 E-value: 1.02e-05

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....*
gi 1804876928  784 NYKALYRFE--ARSHDEMSFNSGDIIQVDEKTigEPGWLYGSFQGNFGWFPCNYV 836
Cdd:cd11901      1 NLPAYVKFNytAEREDELSLVKGTKVIVMEKC--SDGWWRGSYNGQVGWFPSNYV 53

Src homology 3 domain of APC-Stimulated guanine nucleotide Exchange Factor; ASEF, also called ARHGEF4, exists in an autoinhibited form and is activated upon binding of the tumor suppressor APC (adenomatous polyposis coli). GEFs activate small GTPases by exchanging bound GDP for free GTP. ASEF can activate Rac1 or Cdc42. Truncated ASEF, which is found in colorectal cancers, is constitutively active and has been shown to promote angiogenesis and cancer cell migration. ASEF contains a SH3 domain followed by RhoGEF (also called Dbl-homologous or DH) and Pleckstrin Homology (PH) domains. In its autoinhibited form, the SH3 domain of ASEF forms an extensive interface with the DH and PH domains, blocking the Rac binding site. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212906 [Multi-domain] Cd Length: 73 Bit Score: 45.01 E-value: 1.04e-05

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|..
gi 1804876928  924 AQALCSWTAKKDNHLNFSKHDIITVLE-QQENWWFGEVHGGRGWFPKSYVKI 974
Cdd:cd11973     20 AEALWDHVTMDDQELGFKAGDVIEVMDaTNKEWWWGRVLDSEGWFPASFVRL 71

Second C-terminal Src homology 3 domain of Dynamin Binding Protein, also called Tuba, and similar domains; DNMBP or Tuba is a cdc42-specific guanine nucleotide exchange factor (GEF) that contains four N-terminal SH3 domains, a central RhoGEF [or Dbl homology (DH)] domain followed by a Bin/Amphiphysin/Rvs (BAR) domain, and two C-terminal SH3 domains. It provides a functional link between dynamin, Rho GTPase signaling, and actin dynamics. It plays an important role in regulating cell junction configuration. The C-terminal SH3 domains of DNMBP bind to N-WASP and Ena/VASP proteins, which are key regulatory proteins of the actin cytoskeleton. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 213017 [Multi-domain] Cd Length: 57 Bit Score: 44.41 E-value: 1.05e-05

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|...
gi 1804876928 1155 AMYDYVANNEDELNFSKGQLINVLNKDD----PDWWQGEINGVTGLFPSNYVK 1203
Cdd:cd12141      4 AVYTFKARSPNELSVSANQRVRILEFSDltgnKEWWLAEANGQKGYVPSNYIR 56

Third Src Homology 3 domain (SH3C) of Cbl-interacting protein of 85 kDa; CIN85, also called SH3 domain-containing kinase-binding protein 1 (SH3KBP1) or CD2-binding protein 3 (CD2BP3) or Ruk, is an adaptor protein that is involved in the downregulation of receptor tyrosine kinases by facilitating endocytosis through interaction with endophilin-associated ubiquitin ligase Cbl proteins. It is also important in many other cellular processes including vesicle-mediated transport, cytoskeletal remodelling, apoptosis, cell adhesion and migration, and viral infection, among others. CIN85 exists as multiple variants from alternative splicing; the main variant contains three SH3 domains, a proline-rich region, and a C-terminal coiled-coil domain. All of these domains enable CIN85 to bind various protein partners and assemble complexes that have been implicated in many different functions. This alignment model represents the third SH3 domain (SH3C) of CIN85. SH3C has been shown to bind ubiquitin. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212990 [Multi-domain] Cd Length: 56 Bit Score: 44.50 E-value: 1.09e-05

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|
gi 1804876928 1010 LYSYSSVEPGDLTFIEGEEILVTQK---DGEWWTGSIGDRTGIFPSNYVK 1056
Cdd:cd12057      5 LFPYEAQNEDELTIKEGDIVTLISKdciDAGWWEGELNGRRGVFPDNFVK 54

Uncharacterized N-terminal coiled-coil domain of peptidoglycan hydrolase CwlO [Function unknown];

Pssm-ID: 443091 [Multi-domain] Cd Length: 379 Bit Score: 49.83 E-value: 1.11e-05

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1804876928  509 QRNREQEEIVRLNSKKKSLHLELEALNGKHQQISGRLQDVRLRKQTQKTEIEVLDKqcdleimEIKQLQQELQDYQNKLi 588
Cdd:COG3883     17 QIQAKQKELSELQAELEAAQAELDALQAELEELNEEYNELQAELEALQAEIDKLQA-------EIAEAEAEIEERREEL- 88

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1804876928  589 ylvpekqllNERIKNMQLGNTPDLGID-LLHKKSLEkeelcqrlkeqlDALEKETA-SKLSEMDsfnnqlkcgnmddsvl 666
Cdd:COG3883     89 ---------GERARALYRSGGSVSYLDvLLGSESFS------------DFLDRLSAlSKIADAD---------------- 131

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1804876928  667 qcllsllsclnnlflllKELRESYNTQQLALEQLHKIKRDKLKEIERKRSELIQKKKLEDEAIRKAKQGKENLwrESLRK 746
Cdd:COG3883    132 -----------------ADLLEELKADKAELEAKKAELEAKLAELEALKAELEAAKAELEAQQAEQEALLAQL--SAEEA 192

                          250       260       270
                   ....*....|....*....|....*....|....*
gi 1804876928  747 EEEEKQKRLQEEKTQEKVQEEERKVEEKQCEPASA 781
Cdd:COG3883    193 AAEAQLAELEAELAAAEAAAAAAAAAAAAAAAAAA 227

Fifth Src homology 3 domain (or SH3E) of Intersectin-1; Intersectin-1 (ITSN1) is an adaptor protein that functions in exo- and endocytosis, actin cytoskeletal reorganization, and signal transduction. It plays a role in clathrin-coated pit (CCP) formation. It binds to many proteins through its multidomain structure and facilitate the assembly of multimeric complexes. ITSN1 localizes in membranous organelles, CCPs, the Golgi complex, and may be involved in the cell membrane trafficking system. It exists in alternatively spliced short and long isoforms. The short isoform contains two Eps15 homology domains (EH1 and EH2), a coiled-coil region and five SH3 domains (SH3A-E), while the long isoform, in addition, contains RhoGEF (also called Dbl-homologous or DH), Pleckstrin homology (PH) and C2 domains. The fifth SH3 domain (or SH3E) of ITSN1 has been shown to bind many protein partners including SGIP1, Sos1, dynamin1/2, CIN85, c-Cbl, SHIP2, N-WASP, and synaptojanin-1, among others. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212928 [Multi-domain] Cd Length: 54 Bit Score: 44.17 E-value: 1.13e-05

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|.
gi 1804876928  787 ALYRFEARSHDEMSFNSGDIIQVDEKTigEPGWLYGSFQGNFGWFPCNYVE 837
Cdd:cd11995      5 GMYDYTAQNDDELAFSKGQIINVLNKE--DPDWWKGELNGQVGLFPSNYVK 53

MAP7 (E-MAP-115) family; The organization of microtubules varies with the cell type and is presumably controlled by tissue-specific microtubule-associated proteins (MAPs). The 115-kDa epithelial MAP (E-MAP-115/MAP7) has been identified as a microtubule-stabilising protein predominantly expressed in cell lines of epithelial origin. The binding of this microtubule associated protein is nucleotide independent.

Pssm-ID: 461709 [Multi-domain] Cd Length: 153 Bit Score: 46.96 E-value: 1.14e-05

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1804876928  415 EKRRQALMEQQQREAERKAQKEKEEWERKQRELQEQEWKKQLELEKRLEKQRELERQREEERRKEIERREAAKQELERQR 494
Cdd:pfam05672   18 EKRRQAREQREREEQERLEKEEEERLRKEELRRRAEEERARREEEARRLEEERRREEEERQRKAEEEAEEREQREQEEQE 97

                           90       100
                   ....*....|....*....|....*..
gi 1804876928  495 RLEWER----IRRQELLNQRNREQEEI 517
Cdd:pfam05672   98 RLQKQKeeaeAKAREEAERQRQEREKI 124

First Src Homology 3 domain of Sorbin and SH3 domain containing 2 (Sorbs2), also called Arg-binding protein 2 (ArgBP2); Sorbs2 or ArgBP2 is an adaptor protein containing one sorbin homology (SoHo) and three SH3 domains. It regulates actin-dependent processes including cell adhesion, morphology, and migration. It is expressed in many tissues and is abundant in the heart. Like vinexin, it is found in focal adhesion where it interacts with vinculin and afadin. It also localizes in epithelial cell stress fibers and in cardiac muscle cell Z-discs. Sorbs2 has been implicated to play roles in the signaling of c-Arg, Akt, and Pyk2. Other interaction partners of Sorbs2 include c-Abl, flotillin, spectrin, dynamin 1/2, synaptojanin, PTP-PEST, among others. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212853 [Multi-domain] Cd Length: 55 Bit Score: 44.23 E-value: 1.15e-05

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|...
gi 1804876928  922 LKAQALCSWTAKKDNHLNFSKHDIITVLEQ-QENWWFGEVHGGRGWFPKSYVK 973
Cdd:cd11920      1 LPARAVYDFKAQTSKELSFKKGDTVYILRKiDQNWYEGEHHGRVGIFPISYVE 53

Src homology 3 domain of SH3 and multiple ankyrin repeat domains protein 1; Shank1, also called SSTRIP (Somatostatin receptor-interacting protein), is a brain-specific protein that plays a role in the construction of postsynaptic density (PSD) and the maturation of dendritic spines. Mice deficient in Shank1 show altered PSD composition, thinner PSDs, smaller dendritic spines, and weaker basal synaptic transmission, although synaptic plasticity is normal. They show increased anxiety and impaired fear memory, but also show better spatial learning. Shank proteins carry scaffolding functions through multiple sites of protein-protein interaction in its domain architecture, including ankyrin (ANK) repeats, a long proline rich region, as well as SH3, PDZ, and SAM domains. The SH3 domain of Shank binds GRIP, a scaffold protein that binds AMPA receptors and Eph receptors/ligands. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212915 [Multi-domain] Cd Length: 52 Bit Score: 44.23 E-value: 1.16e-05

                           10        20        30        40
                   ....*....|....*....|....*....|....*....|....*....
gi 1804876928 1154 IAMYDYVANNEDELNFSKGQLINVLNKDDPDWWQGEINGVTGLFPSNYV 1202
Cdd:cd11982      4 MAVKPYQSQAEGEISLSKGEKIKVLSVGEGGFWEGQVKGRVGWFPSDCV 52

Src homology 3 domain of Lck Protein Tyrosine Kinase; Lck is a member of the Src subfamily of proteins, which are cytoplasmic (or non-receptor) PTKs. Lck is expressed in T-cells and natural killer cells. It plays a critical role in T-cell maturation, activation, and T-cell receptor (TCR) signaling. Lck phosphorylates ITAM (immunoreceptor tyr activation motif) sequences on several subunits of TCRs, leading to the activation of different second messenger cascades. Phosphorylated ITAMs serve as binding sites for other signaling factor such as Syk and ZAP-70, leading to their activation and propagation of downstream events. In addition, Lck regulates drug-induced apoptosis by interfering with the mitochondrial death pathway. The apototic role of Lck is independent of its primary function in T-cell signaling. Src kinases contain an N-terminal SH4 domain with a myristoylation site, followed by SH3 and SH2 domains, a tyr kinase domain, and a regulatory C-terminal region containing a conserved tyr. They are activated by autophosphorylation at the tyr kinase domain, but are negatively regulated by phosphorylation at the C-terminal tyr by Csk (C-terminal Src Kinase). The SH3 domain of Src kinases contributes to substrate recruitment by binding adaptor proteins/substrates, and regulation of kinase activity through an intramolecular interaction. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212938 [Multi-domain] Cd Length: 54 Bit Score: 44.04 E-value: 1.20e-05

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....*
gi 1804876928 1152 QVIAMYDYVANNEDELNFSKGQLINVLNKdDPDWWQGE--INGVTGLFPSNYVKM 1204
Cdd:cd12005      1 LVVALYSYEPSHDGDLGFEKGEKLRILEQ-SGEWWKAQslTTGQEGFIPFNFVAK 54

Fifth Src homology 3 domain (or SH3E) of Intersectin-1; Intersectin-1 (ITSN1) is an adaptor protein that functions in exo- and endocytosis, actin cytoskeletal reorganization, and signal transduction. It plays a role in clathrin-coated pit (CCP) formation. It binds to many proteins through its multidomain structure and facilitate the assembly of multimeric complexes. ITSN1 localizes in membranous organelles, CCPs, the Golgi complex, and may be involved in the cell membrane trafficking system. It exists in alternatively spliced short and long isoforms. The short isoform contains two Eps15 homology domains (EH1 and EH2), a coiled-coil region and five SH3 domains (SH3A-E), while the long isoform, in addition, contains RhoGEF (also called Dbl-homologous or DH), Pleckstrin homology (PH) and C2 domains. The fifth SH3 domain (or SH3E) of ITSN1 has been shown to bind many protein partners including SGIP1, Sos1, dynamin1/2, CIN85, c-Cbl, SHIP2, N-WASP, and synaptojanin-1, among others. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212928 [Multi-domain] Cd Length: 54 Bit Score: 44.17 E-value: 1.25e-05

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|.
gi 1804876928 1085 YVASGSEQLSLAPGQLILILKKNSSGWWQGELQArgkkrQKGWFPASHVKL 1135
Cdd:cd11995      9 YTAQNDDELAFSKGQIINVLNKEDPDWWKGELNG-----QVGLFPSNYVKL 54

Src homology 3 domain of the CAS (Crk-Associated Substrate) scaffolding protein family member, Breast Cancer Anti-estrogen Resistance 1; BCAR1, also called p130cas or CASS1, is the founding member of the CAS family of scaffolding proteins and was originally identified through its ability to associate with Crk. The name BCAR1 was designated because the human gene was identified in a screen for genes that promote resistance to tamoxifen. It is widely expressed and its deletion is lethal in mice. It plays a role in regulating cell motility, survival, proliferation, transformation, cancer progression, and bacterial pathogenesis. CAS proteins function as molecular scaffolds to regulate protein complexes that are involved in many cellular processes. They share a common domain structure that includes an N-terminal SH3 domain, an unstructured substrate domain that contains many YxxP motifs, a serine-rich four-helix bundle, and a FAT-like C-terminal domain. The SH3 domain of CAS proteins binds to diverse partners including FAK, FRNK, Pyk2, PTP-PEST, DOCK180, among others. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212934 Cd Length: 68 Bit Score: 44.65 E-value: 1.26e-05

                           10        20        30        40        50        60
                   ....*....|....*....|....*....|....*....|....*....|....*....|.
gi 1804876928  921 NLKAQALCSWTAKKDNHLNFSKHDIITVLEQQ----ENWWFGEVHGGRGWFPKSYVKIIPG 977
Cdd:cd12001      2 NVLAKALYDNVAESPDELSFRKGDIMTVLERDtqglDGWWLCSLHGRQGIVPGNRLKILVG 62

Src Homology 3 domain of GTPase Regulator Associated with Focal adhesion kinase and similar proteins; This subfamily is composed of Rho GTPase activating proteins (GAPs) with similarity to GRAF. Members contain an N-terminal BAR domain, followed by a Pleckstrin homology (PH) domain, a Rho GAP domain, and a C-terminal SH3 domain. Although vertebrates harbor four Rho GAPs in the GRAF subfamily including GRAF, GRAF2, GRAF3, and Oligophrenin-1 (OPHN1), only three are included in this model. OPHN1 contains the BAR, PH and GAP domains, but not the C-terminal SH3 domain. GRAF and GRAF2 show GAP activity towards RhoA and Cdc42. GRAF influences Rho-mediated cytoskeletal rearrangements and binds focal adhesion kinase. GRAF2 regulates caspase-activated p21-activated protein kinase-2. The SH3 domain of GRAF and GRAF2 binds PKNbeta, a target of the small GTPase Rho. SH3 domains bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs; they play a role in the regulation of enzymes by intramolecular interactions, changing the subcellular localization of signal pathway components and mediate multiprotein complex assemblies.

Pssm-ID: 212815 [Multi-domain] Cd Length: 54 Bit Score: 44.21 E-value: 1.27e-05

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|.
gi 1804876928 1009 ALYSYSSVEPGDLTFIEGEEILVTQKDGE--WWTGSIGDRTGIFPSNYVKP 1057
Cdd:cd11882      4 ALYACKAEDESELSFEPGQIITNVQPSDEpgWLEGTLNGRTGLIPENYVEF 54

Src Homology 3 domain of Insulin Receptor tyrosine kinase Substrate p53, Brain-specific Angiogenesis Inhibitor 1-Associated Protein 2 (BAIAP2)-Like proteins, and similar proteins; Proteins in this family include IRSp53, BAIAP2L1, BAIAP2L2, and similar proteins. They all contain an Inverse-Bin/Amphiphysin/Rvs (I-BAR) or IMD domain in addition to the SH3 domain. IRSp53, also known as BAIAP2, is a scaffolding protein that takes part in many signaling pathways including Cdc42-induced filopodia formation, Rac-mediated lamellipodia extension, and spine morphogenesis. IRSp53 exists as multiple splicing variants that differ mainly at the C-termini. BAIAP2L1, also called IRTKS (Insulin Receptor Tyrosine Kinase Substrate), serves as a substrate for the insulin receptor and binds the small GTPase Rac. It plays a role in regulating the actin cytoskeleton and colocalizes with F-actin, cortactin, VASP, and vinculin. IRSp53 and IRTKS also mediate the recruitment of effector proteins Tir and EspFu, which regulate host cell actin reorganization, to bacterial attachment sites. BAIAP2L2 co-localizes with clathrin plaques but its function has not been determined. The SH3 domains of IRSp53 and IRTKS have been shown to bind the proline-rich C-terminus of EspFu. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212713 [Multi-domain] Cd Length: 57 Bit Score: 44.24 E-value: 1.31e-05

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|..
gi 1804876928 1084 AYVASGSEQLSLAPGQLI-LILKKNSSGWWQGELQargKKRQKGWFPASHVK 1134
Cdd:cd11779      8 PHAAGGETQLSFEEGDVItLLGPEPRDGWHYGENE---RSGRRGWFPIAYTE 56

Src Homology 3 domain of Src Kinase-Associated Phosphoprotein 2; SKAP2, also called SKAP55-Related (SKAP55R) or SKAP55 homolog (SKAP-HOM or SKAP55-HOM), is an immune cell-specific adaptor protein that plays an important role in adhesion and migration of B-cells and macrophages. Binding partners include ADAP (adhesion and degranulation-promoting adaptor protein), YopH, SHPS1, and HPK1. SKAP2 has also been identified as a substrate for lymphoid-specific tyrosine phosphatase (Lyp), which has been implicated in a wide variety of autoimmune diseases. It contains a pleckstrin homology (PH) domain, a C-terminal SH3 domain, and several tyrosine phosphorylation sites. Like SKAP1, SKAP2 is expected to bind primarily to a proline-rich region of ADAP through its SH3 domain; its degradation may be regulated by ADAP. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212978 Cd Length: 53 Bit Score: 44.12 E-value: 1.31e-05

                           10        20        30        40
                   ....*....|....*....|....*....|....*....|....*....
gi 1804876928 1156 MYDYVANNEDELNFSKGQLINVLNK--DDPDWWQGEINGVTGLFPSNYV 1202
Cdd:cd12045      5 LWDCTGDQPDELSFKRGDTIYILSKeyNRFGWWVGEMKGTIGLVPKAYI 53

N-terminal Src homology 3 domain of Growth factor receptor-bound protein 2 (GRB2) and related proteins; This family includes the adaptor protein GRB2 and related proteins including Drosophila melanogaster Downstream of receptor kinase (DRK), Caenorhabditis elegans Sex muscle abnormal protein 5 (Sem-5), GRB2-related adaptor protein (GRAP), GRAP2, and similar proteins. Family members contain an N-terminal SH3 domain, a central SH2 domain, and a C-terminal SH3 domain. GRB2/Sem-5/DRK is a critical signaling molecule that regulates the Ras pathway by linking tyrosine kinases to the Ras guanine nucleotide releasing protein Sos (son of sevenless), which converts Ras to the active GTP-bound state. GRAP2 plays an important role in T cell receptor (TCR) signaling by promoting the formation of the SLP-76:LAT complex, which couples the TCR to the Ras pathway. GRAP acts as a negative regulator of T cell receptor (TCR)-induced lymphocyte proliferation by downregulating the signaling to the Ras/ERK pathway. The N-terminal SH3 domain of GRB2 binds to Sos and Sos-derived proline-rich peptides. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212738 [Multi-domain] Cd Length: 52 Bit Score: 43.88 E-value: 1.34e-05

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                   ....*....|....*....|....*....|....*....|....*....|...
gi 1804876928  787 ALYRFEARSHDEMSFNSGDIIQV---DEktigEPGWLYGSFQGNFGWFPCNYV 836
Cdd:cd11804      4 AKHDFKATAEDELSFKKGSILKVlnmED----DPNWYKAELDGKEGLIPKNYI 52

Src Homology 3 domain of Tec (Tyrosine kinase expressed in hepatocellular carcinoma); Tec is a cytoplasmic (or nonreceptor) tyr kinase containing Src homology protein interaction domains (SH3, SH2) N-terminal to the catalytic tyr kinase domain. It also contains an N-terminal pleckstrin homology (PH) domain, which binds the products of PI3K and allows membrane recruitment and activation, and the Tec homology (TH) domain, which contains proline-rich and zinc-binding regions. It is more widely-expressed than other Tec subfamily kinases. Tec is found in endothelial cells, both B- and T-cells, and a variety of myeloid cells including mast cells, erythroid cells, platelets, macrophages and neutrophils. Tec is a key component of T-cell receptor (TCR) signaling, and is important in TCR-stimulated proliferation, IL-2 production and phospholipase C-gamma1 activation. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212838 [Multi-domain] Cd Length: 56 Bit Score: 44.03 E-value: 1.35e-05

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                   ....*....|....*....|....*....|....*....|....*....|....*
gi 1804876928 1008 IALYSYSSVEPGDLTFIEGEEILVTQK-DGEWWTGSigDR---TGIFPSNYVKPK 1058
Cdd:cd11905      4 VAMYDFQPTEPHDLRLETGEEYVILEKnDVHWWKAR--DKygkEGYIPSNYVTGK 56

Third Src homology 3 domain (or SH3C) of Intersectin; Intersectins (ITSNs) are adaptor proteins that function in exo- and endocytosis, actin cytoskeletal reorganization, and signal transduction. They are essential for initiating clathrin-coated pit formation. They bind to many proteins through their multidomain structure and facilitate the assembly of multimeric complexes. Vertebrates contain two ITSN proteins, ITSN1 and ITSN2, which exist in alternatively spliced short and long isoforms. The short isoforms contain two Eps15 homology domains (EH1 and EH2), a coiled-coil region and five SH3 domains (SH3A-E), while the long isoforms, in addition, contain RhoGEF (also called Dbl-homologous or DH), Pleckstrin homology (PH) and C2 domains. ITSN1 and ITSN2 are both widely expressed, with variations depending on tissue type and stage of development. The third SH3 domain (or SH3C) of ITSN1 has been shown to bind many proteins including dynamin1/2, CIN85, c-Cbl, SHIP2, Reps1, synaptojanin-1, and WNK, among others. The SH3C of ITSN2 has been shown to bind the K15 protein of Kaposi's sarcoma-associated herpesvirus. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212772 [Multi-domain] Cd Length: 52 Bit Score: 43.94 E-value: 1.35e-05

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                   ....*....|....*....|....*....|....*....|....*....|....*
gi 1804876928  784 NYKALYRFEARSHDEMSFNSGDIIQVDEKTiGEpgWLYGSFQGNFGWFPCNYVEK 838
Cdd:cd11838      1 EYIALYPYESNEPGDLTFNAGDVILVTKKD-GE--WWTGTIGDRTGIFPSNYVRP 52

Src Homology 3 domain of Abelson helper integration site-1 (AHI-1); AHI-1, also called Jouberin, is expressed in high levels in the brain, gonad tissues, and skeletal muscle. It is an adaptor protein that interacts with the small GTPase Rab8a and regulates it distribution and function, affecting cilium formation and vesicle transport. Mutations in the AHI-1 gene can cause Joubert syndrome, a disorder characterized by brainstem malformations, cerebellar aplasia/hypoplasia, and retinal dystrophy. AHI-1 variation is also associated with susceptibility to schizophrenia and type 2 diabetes mellitus progression. AHI-1 contains WD40 and SH3 domains. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212746 [Multi-domain] Cd Length: 52 Bit Score: 44.04 E-value: 1.35e-05

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                   ....*....|....*....|....*....|....*....|....*....
gi 1804876928 1085 YVASGSEQLSLAPGQLILILKKNSSGWWQGELqARGkkrQKGWFPASHV 1133
Cdd:cd11812      8 YTANRSDELTIHRGDIIRVLYKDNDNWWFGSL-VNG---QQGYFPANYV 52

Src homology 3 domain of eumetazoan Actin-binding protein 1; Abp1, also called drebrin-like protein, is an adaptor protein that functions in receptor-mediated endocytosis and vesicle trafficking. It contains an N-terminal actin-binding module, the actin-depolymerizing factor (ADF) homology domain, a helical domain, and a C-terminal SH3 domain. Mammalian Abp1, unlike yeast Abp1, does not contain an acidic domain that interacts with the Arp2/3 complex. It regulates actin dynamics indirectly by interacting with dynamin and WASP family proteins. Abp1 deficiency causes abnormal organ structure and function of the spleen, heart, and lung of mice. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212893 [Multi-domain] Cd Length: 54 Bit Score: 43.93 E-value: 1.37e-05

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                   ....*....|....*....|....*....|....*....|....*....|
gi 1804876928 1009 ALYSYSSVEPGDLTFIEGEEIL-VTQKDGEWWTGSIGD-RTGIFPSNYVK 1056
Cdd:cd11960      4 ALYDYQAADDTEISFDPGDIITdIEQIDEGWWRGTGPDgTYGLFPANYVE 53

Second Src homology 3 domain of ADAM-binding protein Eve-1; Eve-1, also called SH3 domain-containing protein 19 (SH3D19) or EEN-binding protein (EBP), exists in multiple alternatively spliced isoforms. The longest isoform contains five SH3 domain in the C-terminal region and seven proline-rich motifs in the N-terminal region. It is abundantly expressed in skeletal muscle and heart, and may be involved in regulating the activity of ADAMs (A disintegrin and metalloproteases). Eve-1 interacts with EEN, an endophilin involved in endocytosis and may be the target of the MLL-EEN fusion protein that is implicated in leukemogenesis. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212749 [Multi-domain] Cd Length: 52 Bit Score: 44.09 E-value: 1.41e-05

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                   ....*....|....*....|....*....|....*....|....*....|
gi 1804876928 1008 IALYSYSSVEPGDLTFIEGEEILVTQK-DGEWWTGSIGDRTGIFPSNYVK 1056
Cdd:cd11815      3 VVLHDFPAEHSDDLSLNSGEIVYLLEKiDTEWYRGKCKNTTGIFPANHVK 52

C-terminal (or second) Src homology 3 domain of VAV proteins; VAV proteins function both as cytoplasmic guanine nucleotide exchange factors (GEFs) for Rho GTPases and scaffold proteins and they play important roles in cell signaling by coupling cell surface receptors to various effector functions. They play key roles in processes that require cytoskeletal reorganization including immune synapse formation, phagocytosis, cell spreading, and platelet aggregation, among others. Vertebrates have three VAV proteins (VAV1, VAV2, and VAV3). VAV proteins contain several domains that enable their function: N-terminal calponin homology (CH), acidic, RhoGEF (also called Dbl-homologous or DH), Pleckstrin Homology (PH), C1 (zinc finger), SH2, and two SH3 domains. The SH3 domain of VAV is involved in the localization of proteins to specific sites within the cell, by interacting with proline-rich sequences within target proteins. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212764 [Multi-domain] Cd Length: 54 Bit Score: 44.16 E-value: 1.43e-05

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                   ....*....|....*....|....*....|....*....|....*....|..
gi 1804876928  924 AQALCSWTAKKDNHLNFSKHDIITVLEQ--QENWWFGEVHGGRGWFPKSYVK 973
Cdd:cd11830      2 AKARYDFCARDMRELSLKEGDVVKIYNKkgQQGWWRGEINGRIGWFPSTYVE 53

Third Src Homology 3 domain (SH3C) of CD2-associated protein and similar proteins; This subfamily is composed of the third SH3 domain (SH3C) of CD2AP, CIN85 (Cbl-interacting protein of 85 kDa), and similar domains. CD2AP and CIN85 are adaptor proteins that bind to protein partners and assemble complexes that have been implicated in T cell activation, kidney function, and apoptosis of neuronal cells. They also associate with endocytic proteins, actin cytoskeleton components, and other adaptor proteins involved in receptor tyrosine kinase (RTK) signaling. CD2AP and the main isoform of CIN85 contain three SH3 domains, a proline-rich region, and a C-terminal coiled-coil domain. All of these domains enable CD2AP and CIN85 to bind various protein partners and assemble complexes that have been implicated in many different functions. SH3C of both proteins have been shown to bind to ubiquitin. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212808 [Multi-domain] Cd Length: 55 Bit Score: 43.88 E-value: 1.45e-05

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                   ....*....|....*....|....*....|....*....|....*....|....*
gi 1804876928  923 KAQALCSWTAKKDNHLNFSKHDIITVLE---QQENWWFGEVHGGRGWFPKSYVKI 974
Cdd:cd11875      1 KARVLFDYEAENEDELTLREGDIVTILSkdcEDKGWWKGELNGKRGVFPDNFVEP 55

C-terminal (or second) Src homology 3 domain of VAV1 protein; VAV1 is expressed predominantly in the hematopoietic system and it plays an important role in the development and activation of B and T cells. It is activated by tyrosine phosphorylation to function as a guanine nucleotide exchange factor (GEF) for Rho GTPases following cell surface receptor activation, triggering various effects such as cytoskeletal reorganization, transcription regulation, cell cycle progression, and calcium mobilization. It also serves as a scaffold protein and has been shown to interact with Ku70, Socs1, Janus kinase 2, SIAH2, S100B, Abl gene, ZAP-70, SLP76, and Syk, among others. VAV proteins contain several domains that enable their function: N-terminal calponin homology (CH), acidic, RhoGEF (also called Dbl-homologous or DH), Pleckstrin Homology (PH), C1 (zinc finger), SH2, and two SH3 domains. The C-terminal SH3 domain of Vav1 interacts with a wide variety of proteins including cytoskeletal regulators (zyxin), RNA-binding proteins (Sam68), transcriptional regulators, viral proteins, and dynamin 2. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212909 [Multi-domain] Cd Length: 54 Bit Score: 44.16 E-value: 1.46e-05

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                   ....*....|....*....|....*....|....*....|....*....|.
gi 1804876928 1085 YVASGSEQLSLAPGQLILIL-KKNSSGWWQGELQARgkkrqKGWFPASHVK 1134
Cdd:cd11976      8 FCARDRSELSLKEGDIIKILnKKGQQGWWRGEIYGR-----VGWFPANYVE 53

Src homology 3 domain of Type I fungal Myosins; Type I myosins (myosin-I) are actin-dependent motors in endocytic actin structures and actin patches. They play roles in membrane traffic in endocytic and secretory pathways, cell motility, and mechanosensing. Saccharomyces cerevisiae has two myosins-I, Myo3 and Myo5, which are involved in endocytosis and the polarization of the actin cytoskeleton. Myosin-I contains an N-terminal actin-activated ATPase, a phospholipid-binding TH1 (tail homology 1) domain, and a C-terminal extension which includes an F-actin-binding TH2 domain, an SH3 domain, and an acidic peptide that participates in activating the Arp2/3complex. The SH3 domain of myosin-I is required for myosin-I-induced actin polymerization. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212792 [Multi-domain] Cd Length: 55 Bit Score: 43.91 E-value: 1.46e-05

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                   ....*....|....*....|....*....|....*....|....*....|....*...
gi 1804876928  785 YKALYRFEARSHDEMSFNSGDIIQVDEKTIGepGW-----LYGSFQgnfGWFPCNYVE 837
Cdd:cd11858      2 YKALYDFAGSVANELSLKKDDIVYIVQKEDN--GWwlakkLDESKE---GWVPAAYLE 54

Src homology 3 domain of CAS (Crk-Associated Substrate) scaffolding protein family member, Embryonal Fyn-associated Substrate; EFS is also called HEFS, CASS3 (Cas scaffolding protein family member 3) or SIN (Src-interacting protein). It was identified based on interactions with the Src kinases, Fyn and Yes. It plays a role in thymocyte development and acts as a negative regulator of T cell proliferation. CAS proteins function as molecular scaffolds to regulate protein complexes that are involved in many cellular processes. They share a common domain structure that includes an N-terminal SH3 domain, an unstructured substrate domain that contains many YxxP motifs, a serine-rich four-helix bundle, and a FAT-like C-terminal domain. The SH3 domain of CAS proteins binds to diverse partners including FAK, FRNK, Pyk2, PTP-PEST, DOCK180, among others. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212936 Cd Length: 62 Bit Score: 44.11 E-value: 1.47e-05

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                   ....*....|....*....|....*....|....*....|....*....|...
gi 1804876928 1155 AMYDYVANNEDELNFSKGQLINVLNKDDPD---WWQGEINGVTGLFPSNYVKM 1204
Cdd:cd12003      5 ALYDNAAESPEELSFRRGDVLMVLKREHGSlpgWWLCSLHGQQGIAPANRLRL 57

Src Homology 3 domain of Sorting Nexin 9 and similar proteins; Sorting nexins (SNXs) are Phox homology (PX) domain containing proteins that are involved in regulating membrane traffic and protein sorting in the endosomal system. SNXs differ from each other in their lipid-binding specificity, subcellular localization and specific function in the endocytic pathway. This subfamily consists of SH3 domain containing SNXs including SNX9, SNX18, SNX33, and similar proteins. SNX9 is localized to plasma membrane endocytic sites and acts primarily in clathrin-mediated endocytosis, while SNX18 is localized to peripheral endosomal structures, and acts in a trafficking pathway that is clathrin-independent but relies on AP-1 and PACS1. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212697 [Multi-domain] Cd Length: 55 Bit Score: 43.85 E-value: 1.55e-05

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                   ....*....|....*....|....*....|....*....|....*....|....
gi 1804876928  785 YKALYRFEARSHDEMSFNSGDIIQVDEKTIGEpGWLYG-SFQGNFGWFPCNYVE 837
Cdd:cd11763      2 VRALYDFDSQPSGELSLRAGEVLTITRQDVGD-GWLEGrNSRGEVGLFPSSYVE 54

First Src homology 3 domain (or SH3A) of Intersectin-1; Intersectin-1 (ITSN1) is an adaptor protein that functions in exo- and endocytosis, actin cytoskeletal reorganization, and signal transduction. It plays a role in clathrin-coated pit (CCP) formation. It binds to many proteins through its multidomain structure and facilitate the assembly of multimeric complexes. ITSN1 localizes in membranous organelles, CCPs, the Golgi complex, and may be involved in the cell membrane trafficking system. It exists in alternatively spliced short and long isoforms. The short isoform contains two Eps15 homology domains (EH1 and EH2), a coiled-coil region and five SH3 domains (SH3A-E), while the long isoform, in addition, contains RhoGEF (also called Dbl-homologous or DH), Pleckstrin homology (PH) and C2 domains. The first SH3 domain (or SH3A) of ITSN1 has been shown to bind many proteins including Sos1, dynamin1/2, CIN85, c-Cbl, PI3K-C2, SHIP2, N-WASP, and CdGAP, among others. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212920 [Multi-domain] Cd Length: 55 Bit Score: 43.83 E-value: 1.62e-05

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|.
gi 1804876928 1155 AMYDYVANNEDELNFSKGQLINVLNKD--DPDWWQGEINGVTGLFPSNYVK 1203
Cdd:cd11987      4 ALYPFEARSHDEITIQPGDIVMVDESQtgEPGWLGGELKGKTGWFPANYAE 54

Src homology 3 domain of SH3 domain containing Ysc84-like 1 (SH3YL1) protein; SH3YL1 localizes to the plasma membrane and is required for dorsal ruffle formation. It binds phosphoinositides (PIs) with high affinity through its N-terminal SYLF domain (also called DUF500). In addition, SH3YL1 contains a C-terminal SH3 domain which has been reported to bind to N-WASP, dynamin 2, and SHIP2 (a PI 5-phosphatase). SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212775 Cd Length: 54 Bit Score: 43.92 E-value: 1.63e-05

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|.
gi 1804876928  786 KALYRFEARSHDEMSFNSGDIIQVDEKTIGEPGWLYGSFQGNFGWFPCNYV 836
Cdd:cd11841      3 TALYSFEGQQPCDLSFQAGDRITVLTRTDSQFDWWEGRLRGRVGIFPANYV 53

Src homology 3 domain of Abl Interactor 1; Abi1, also called e3B1, is a central regulator of actin cytoskeletal reorganization through interactions with many protein complexes. It is part of WAVE, a nucleation-promoting factor complex, that links Rac 1 activation to actin polymerization causing lamellipodia protrusion at the plasma membrane. Abi1 interact with formins to promote protrusions at the leading edge of motile cells. It also is a target of alpha4 integrin, regulating membrane protrusions at sites of integrin engagement. Abi proteins are adaptor proteins serving as binding partners and substrates of Abl tyrosine kinases. They are involved in regulating actin cytoskeletal reorganization and play important roles in membrane-ruffling, endocytosis, cell motility, and cell migration. Abi proteins contain a homeobox homology domain, a proline-rich region, and a SH3 domain. The SH3 domain of Abi binds to a PxxP motif in Abl. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212904 [Multi-domain] Cd Length: 59 Bit Score: 43.86 E-value: 1.63e-05

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|
gi 1804876928 1008 IALYSYSSVEPGDLTFIEGEEILVTQK-DGEWWTGSIGDRTGIFPSNYVK 1056
Cdd:cd11971      3 VAIYDYSKDKDDELSFMEGAIIYVIKKnDDGWYEGVCNGVTGLFPGNYVE 52

First C-terminal Src homology 3 domain of Fungal Actin-binding protein 1; Abp1 is an adaptor protein that functions in receptor-mediated endocytosis and vesicle trafficking. It contains an N-terminal actin-binding module, the actin-depolymerizing factor (ADF) homology domain, a central proline-rich region, and a C-terminal SH3 domain (many yeast Abp1 proteins contain two C-terminal SH3 domains). Yeast Abp1 also contains two acidic domains that bind directly to the Arp2/3 complex, which is required to initiate actin polymerization. The SH3 domain of yeast Abp1 binds and localizes the kinases, Ark1p and Prk1p, which facilitate actin patch disassembly following vesicle internalization. It also mediates the localization to the actin patch of the synaptojanin-like protein, Sjl2p, which plays a key role in endocytosis. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212895 [Multi-domain] Cd Length: 54 Bit Score: 44.02 E-value: 1.65e-05

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....
gi 1804876928  923 KAQALCSWTAKKDNHLNFSKHDIITVLEQ-QENWWFGE-VHGGRGWFPKSYVKI 974
Cdd:cd11962      1 RAVVLYDYEKDEDNEIELVEGEIVTNIEMvDEDWWMGTnSKGESGLFPSNYVEL 54

Second Src Homology 3 domain of Nck1 adaptor protein; Nck1 (also called Nckalpha) plays a crucial role in connecting signaling pathways of tyrosine kinase receptors and important effectors in actin dynamics and cytoskeletal remodeling. It binds and activates RasGAP, resulting in the downregulation of Ras. It is also involved in the signaling of endothilin-mediated inhibition of cell migration. Nck adaptor proteins regulate actin cytoskeleton dynamics by linking proline-rich effector molecules to protein tyrosine kinases and phosphorylated signaling intermediates. They contain three SH3 domains and a C-terminal SH2 domain. They function downstream of the PDGFbeta receptor and are involved in Rho GTPase signaling and actin dynamics. Vertebrates contain two Nck adaptor proteins: Nck1 (also called Nckalpha) and Nck2, which show partly overlapping functions but also bind distinct targets. The second SH3 domain of Nck appears to prefer ligands containing the APxxPxR motif. SH3 domains are protein interaction domains that usually bind to proline-rich ligands with moderate affinity and selectivity, preferentially a PxxP motif. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212834 [Multi-domain] Cd Length: 55 Bit Score: 43.87 E-value: 1.67e-05

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|...
gi 1804876928  921 NLKAQALCSWTAKKDNHLNFSKHDIITVLEQ-QENWWFGEVHGGRGWFPKSYV 972
Cdd:cd11901      1 NLPAYVKFNYTAEREDELSLVKGTKVIVMEKcSDGWWRGSYNGQVGWFPSNYV 53

C-terminal (or second) Src homology 3 domain of VAV1 protein; VAV1 is expressed predominantly in the hematopoietic system and it plays an important role in the development and activation of B and T cells. It is activated by tyrosine phosphorylation to function as a guanine nucleotide exchange factor (GEF) for Rho GTPases following cell surface receptor activation, triggering various effects such as cytoskeletal reorganization, transcription regulation, cell cycle progression, and calcium mobilization. It also serves as a scaffold protein and has been shown to interact with Ku70, Socs1, Janus kinase 2, SIAH2, S100B, Abl gene, ZAP-70, SLP76, and Syk, among others. VAV proteins contain several domains that enable their function: N-terminal calponin homology (CH), acidic, RhoGEF (also called Dbl-homologous or DH), Pleckstrin Homology (PH), C1 (zinc finger), SH2, and two SH3 domains. The C-terminal SH3 domain of Vav1 interacts with a wide variety of proteins including cytoskeletal regulators (zyxin), RNA-binding proteins (Sam68), transcriptional regulators, viral proteins, and dynamin 2. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212909 [Multi-domain] Cd Length: 54 Bit Score: 43.78 E-value: 1.70e-05

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|
gi 1804876928 1009 ALYSYSSVEPGDLTFIEGEEILVTQKDGE--WWTGSIGDRTGIFPSNYVK 1056
Cdd:cd11976      4 ARYDFCARDRSELSLKEGDIIKILNKKGQqgWWRGEIYGRVGWFPANYVE 53

Src Homology 3 domain of Mixed Lineage Kinase 4; MLK4 is a Serine/Threonine Kinase (STK), catalyzing the transfer of the gamma-phosphoryl group from ATP to S/T residues on protein substrates. MLKs act as mitogen-activated protein kinase kinase kinases (MAP3Ks, MKKKs, MAPKKKs), which phosphorylate and activate MAPK kinases (MAPKKs or MKKs or MAP2Ks), which in turn phosphorylate and activate MAPKs during signaling cascades that are important in mediating cellular responses to extracellular signals. MLKs play roles in immunity and inflammation, as well as in cell death, proliferation, and cell cycle regulation. The specific function of MLK4 is yet to be determined. Mutations in the kinase domain of MLK4 have been detected in colorectal cancers. MLK4 contains an SH3 domain, a catalytic kinase domain, a leucine zipper, a proline-rich region, and a CRIB domain that mediates binding to GTP-bound Cdc42 and Rac. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212991 [Multi-domain] Cd Length: 58 Bit Score: 43.78 E-value: 1.73e-05

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....
gi 1804876928 1085 YVASGSEQLSLAPGQLILILKKNSS-----GWWQGELQARgkkrqKGWFPASHV 1133
Cdd:cd12058      8 YEASGEDELSLRRGDVVEVLSQDAAvsgddGWWAGKIRHR-----LGIFPANYV 56

Src homology 3 domain of CAS (Crk-Associated Substrate) scaffolding protein family member 4; CASS4, also called HEPL (HEF1-EFS-p130Cas-like), localizes to focal adhesions and plays a role in regulating FAK activity, focal adhesion integrity, and cell spreading. It is most abundant in blood cells and lung tissue, and is also found in high levels in leukemia and ovarian cell lines. CAS proteins function as molecular scaffolds to regulate protein complexes that are involved in many cellular processes. They share a common domain structure that includes an N-terminal SH3 domain, an unstructured substrate domain that contains many YxxP motifs, a serine-rich four-helix bundle, and a FAT-like C-terminal domain. The SH3 domain of CAS proteins binds to diverse partners including FAK, FRNK, Pyk2, PTP-PEST, DOCK180, among others. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212933 Cd Length: 57 Bit Score: 43.71 E-value: 1.78e-05

                           10        20        30        40
                   ....*....|....*....|....*....|....*....|....*....
gi 1804876928 1155 AMYDYVANNEDELNFSKGQLINVLNKDDPD---WWQGEINGVTGLFPSN 1200
Cdd:cd12000      5 ALYDNKADCSDELAFRRGDILTVLEQNVPGsegWWKCLLHGRQGLAPAN 53

Src Homology 3 domain of Sorting Nexin 9 and similar proteins; Sorting nexins (SNXs) are Phox homology (PX) domain containing proteins that are involved in regulating membrane traffic and protein sorting in the endosomal system. SNXs differ from each other in their lipid-binding specificity, subcellular localization and specific function in the endocytic pathway. This subfamily consists of SH3 domain containing SNXs including SNX9, SNX18, SNX33, and similar proteins. SNX9 is localized to plasma membrane endocytic sites and acts primarily in clathrin-mediated endocytosis, while SNX18 is localized to peripheral endosomal structures, and acts in a trafficking pathway that is clathrin-independent but relies on AP-1 and PACS1. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212697 [Multi-domain] Cd Length: 55 Bit Score: 43.85 E-value: 1.78e-05

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....*
gi 1804876928  923 KAQALCSWTAKKDNHLNFSKHDIITVLEQQ--ENWWFGE-VHGGRGWFPKSYVKI 974
Cdd:cd11763      1 KVRALYDFDSQPSGELSLRAGEVLTITRQDvgDGWLEGRnSRGEVGLFPSSYVEI 55

Src homology 3 domain of the CAS (Crk-Associated Substrate) scaffolding protein family member, Breast Cancer Anti-estrogen Resistance 1; BCAR1, also called p130cas or CASS1, is the founding member of the CAS family of scaffolding proteins and was originally identified through its ability to associate with Crk. The name BCAR1 was designated because the human gene was identified in a screen for genes that promote resistance to tamoxifen. It is widely expressed and its deletion is lethal in mice. It plays a role in regulating cell motility, survival, proliferation, transformation, cancer progression, and bacterial pathogenesis. CAS proteins function as molecular scaffolds to regulate protein complexes that are involved in many cellular processes. They share a common domain structure that includes an N-terminal SH3 domain, an unstructured substrate domain that contains many YxxP motifs, a serine-rich four-helix bundle, and a FAT-like C-terminal domain. The SH3 domain of CAS proteins binds to diverse partners including FAK, FRNK, Pyk2, PTP-PEST, DOCK180, among others. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212934 Cd Length: 68 Bit Score: 44.26 E-value: 1.85e-05

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|...
gi 1804876928 1155 AMYDYVANNEDELNFSKGQLINVLNKDDP---DWWQGEINGVTGLFPSNYVKM 1204
Cdd:cd12001      7 ALYDNVAESPDELSFRKGDIMTVLERDTQgldGWWLCSLHGRQGIVPGNRLKI 59

Second Src Homology 3 domain of SH3 domain containing ring finger proteins; This model represents the second SH3 domain of SH3RF1 (or POSH), SH3RF2 (or POSHER), SH3RF3 (POSH2), and similar domains. Members of this family are scaffold proteins that function as E3 ubiquitin-protein ligases. They all contain an N-terminal RING finger domain and multiple SH3 domains; SH3RF1 and SH3RF3 have four SH3 domains while SH3RF2 has three. SH3RF1 plays a role in calcium homeostasis through the control of the ubiquitin domain protein Herp. It may also have a role in regulating death receptor mediated and JNK mediated apoptosis. SH3RF3 interacts with p21-activated kinase 2 (PAK2) and GTP-loaded Rac1. It may play a role in regulating JNK mediated apoptosis in certain conditions. SH3RF2 acts as an anti-apoptotic regulator of the JNK pathway by binding to and promoting the degradation of SH3RF1. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212721 [Multi-domain] Cd Length: 53 Bit Score: 43.48 E-value: 1.86e-05

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|...
gi 1804876928 1152 QVIAMYDYVANNEDE---LNFSKGQLINVLNKDDPDWWQGEINGVTGLFPSNY 1201
Cdd:cd11787      1 QCKALYDFEMKDEDEkdcLTFKKGDVITVIRRVDENWAEGRLGDKIGIFPISF 53

Second Src homology 3 domain (or SH3B) of Intersectin-2; Intersectin-2 (ITSN2) is an adaptor protein that functions in exo- and endocytosis, actin cytoskeletal reorganization, and signal transduction. It plays a role in clathrin-coated pit (CCP) formation. It binds to many proteins through its multidomain structure and facilitate the assembly of multimeric complexes. ITSN2 also functions as a specific GEF for Cdc42 activation in epithelial morphogenesis, and is required in mitotic spindle orientation. It exists in alternatively spliced short and long isoforms. The short isoform contains two Eps15 homology domains (EH1 and EH2), a coiled-coil region and five SH3 domains (SH3A-E), while the long isoform, in addition, contains RhoGEF (also called Dbl-homologous or DH), Pleckstrin homology (PH) and C2 domains. The second SH3 domain (or SH3B) of ITSN2 is expected to bind protein partners, similar to ITSN1 which has been shown to bind WNK and CdGAP. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212923 [Multi-domain] Cd Length: 52 Bit Score: 43.49 E-value: 1.88e-05

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|..
gi 1804876928  786 KALYRFEARSHDEMSFNSGDIIQVDEKtigEPGWLYGSFQGNFGWFPCNYVE 837
Cdd:cd11990      3 QALCSWTAKKDNHLNFSKNDIITVLEQ---QENWWFGEVHGGRGWFPKSYVK 51

First Src homology 3 domain (or SH3A) of Intersectin-2; Intersectin-2 (ITSN2) is an adaptor protein that functions in exo- and endocytosis, actin cytoskeletal reorganization, and signal transduction. It plays a role in clathrin-coated pit (CCP) formation. It binds to many proteins through its multidomain structure and facilitate the assembly of multimeric complexes. ITSN2 also functions as a specific GEF for Cdc42 activation in epithelial morphogenesis, and is required in mitotic spindle orientation. It exists in alternatively spliced short and long isoforms. The short isoform contains two Eps15 homology domains (EH1 and EH2), a coiled-coil region and five SH3 domains (SH3A-E), while the long isoform, in addition, contains RhoGEF (also called Dbl-homologous or DH), Pleckstrin homology (PH) and C2 domains. The first SH3 domain (or SH3A) of ITSN2 is expected to bind many protein partners, similar to ITSN1 which has been shown to bind Sos1, dynamin1/2, CIN85, c-Cbl, PI3K-C2, SHIP2, N-WASP, and CdGAP, among others. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212921 [Multi-domain] Cd Length: 57 Bit Score: 43.71 E-value: 1.90e-05

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|.
gi 1804876928 1155 AMYDYVANNEDELNFSKGQLINVLNKD--DPDWWQGEINGVTGLFPSNYVK 1203
Cdd:cd11988      6 ALYPFEARNHDEMSFNAGDIIQVDEKTvgEPGWLYGSFQGNFGWFPCNYVE 56

Src homology 3 domain of Protein kinase C and Casein kinase Substrate in Neurons (PACSIN) proteins; PACSINs, also called Synaptic dynamin-associated proteins (Syndapins), act as regulators of cytoskeletal and membrane dynamics. They bind both dynamin and Wiskott-Aldrich syndrome protein (WASP), and may provide direct links between the actin cytoskeletal machinery through WASP and dynamin-dependent endocytosis. Vetebrates harbor three isoforms with distinct expression patterns and specific functions. PACSINs contain an N-terminal F-BAR domain and a C-terminal SH3 domain. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212777 [Multi-domain] Cd Length: 53 Bit Score: 43.56 E-value: 1.93e-05

                           10        20        30        40
                   ....*....|....*....|....*....|....*....|....*....
gi 1804876928 1009 ALYSYSSVEPGDLTFIEGEEIL-VTQKDGE-WWTGSIGDRTGIFPSNYV 1055
Cdd:cd11843      4 ALYDYEGQESDELSFKAGDILTkLEEEDEQgWCKGRLDGRVGLYPANYV 52

Pleckstrin homology (PH) domain; PH domains have diverse functions, but in general are involved in targeting proteins to the appropriate cellular location or in the interaction with a binding partner. They share little sequence conservation, but all have a common fold, which is electrostatically polarized. Less than 10% of PH domains bind phosphoinositide phosphates (PIPs) with high affinity and specificity. PH domains are distinguished from other PIP-binding domains by their specific high-affinity binding to PIPs with two vicinal phosphate groups: PtdIns(3,4)P2, PtdIns(4,5)P2 or PtdIns(3,4,5)P3 which results in targeting some PH domain proteins to the plasma membrane. A few display strong specificity in lipid binding. Any specificity is usually determined by loop regions or insertions in the N-terminus of the domain, which are not conserved across all PH domains. PH domains are found in cellular signaling proteins such as serine/threonine kinase, tyrosine kinases, regulators of G-proteins, endocytotic GTPases, adaptors, as well as cytoskeletal associated molecules and in lipid associated enzymes.

Pssm-ID: 275388 [Multi-domain] Cd Length: 92 Bit Score: 44.84 E-value: 2.00e-05

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1804876928 1458 HSGKLYKT-----KSNKELHGFLFNDFLLltymvkqfavssgseklFSSKSNAQFKMYKTPIFLNEVLVKLPTDPSSDEP 1532
Cdd:cd00821      1 KEGYLLKRgggglKSWKKRWFVLFEGVLL-----------------YYKSKKDSSYKPKGSIPLSGILEVEEVSPKERPH 63

                           90       100
                   ....*....|....*....|....*....
gi 1804876928 1533 VFHISH-IDRVYTLRTDNINERTAWVQKI 1560
Cdd:cd00821     64 CFELVTpDGRTYYLQADSEEERQEWLKAL 92

Src homology 3 domain of Fyn and Yrk Protein Tyrosine Kinases; Fyn and Yrk (Yes-related kinase) are members of the Src subfamily of proteins, which are cytoplasmic (or non-receptor) PTKs. Fyn, together with Lck, plays a critical role in T-cell signal transduction by phosphorylating ITAM (immunoreceptor tyr activation motif) sequences on T-cell receptors, ultimately leading to the proliferation and differentiation of T-cells. In addition, Fyn is involved in the myelination of neurons, and is implicated in Alzheimer's and Parkinson's diseases. Yrk has been detected only in chickens. It is primarily found in neuronal and epithelial cells and in macrophages. It may play a role in inflammation and in response to injury. Src kinases contain an N-terminal SH4 domain with a myristoylation site, followed by SH3 and SH2 domains, a tyr kinase domain, and a regulatory C-terminal region containing a conserved tyr. They are activated by autophosphorylation at the tyr kinase domain, but are negatively regulated by phosphorylation at the C-terminal tyr by Csk (C-terminal Src Kinase). The SH3 domain of Src kinases contributes to substrate recruitment by binding adaptor proteins/substrates, and regulation of kinase activity through an intramolecular interaction. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212939 [Multi-domain] Cd Length: 56 Bit Score: 43.50 E-value: 2.03e-05

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....*
gi 1804876928 1007 YIALYSYSSVEPGDLTFIEGEEI-LVTQKDGEWWTG---SIGDrTGIFPSNYVKP 1057
Cdd:cd12006      3 FVALYDYEARTEDDLSFHKGEKFqILNSSEGDWWEArslTTGE-TGYIPSNYVAP 56

exonuclease SbcC; All proteins in this family for which functions are known are part of an exonuclease complex with sbcD homologs. This complex is involved in the initiation of recombination to regulate the levels of palindromic sequences in DNA. This family is based on the phylogenomic analysis of JA Eisen (1999, Ph.D. Thesis, Stanford University). [DNA metabolism, DNA replication, recombination, and repair]

Pssm-ID: 129705 [Multi-domain] Cd Length: 1042 Bit Score: 49.58 E-value: 2.04e-05

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1804876928  411 NVELEKRRQALMEQQQREA------ERKAQKEKEEWERKQrELQEQEW---KKQLELEKRLEKQRELERQREEERRKEIE 481
Cdd:TIGR00618  458 KIHLQESAQSLKEREQQLQtkeqihLQETRKKAVVLARLL-ELQEEPCplcGSCIHPNPARQDIDNPGPLTRRMQRGEQT 536

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1804876928  482 RREAAKQELERQRRLEWERIRRQELLNQRNREQEEIVRLNSKKKSLHLELEALngkhQQISGRLQD---------VRLRK 552
Cdd:TIGR00618  537 YAQLETSEEDVYHQLTSERKQRASLKEQMQEIQQSFSILTQCDNRSKEDIPNL----QNITVRLQDlteklseaeDMLAC 612

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1804876928  553 QTQKTEIEVLDKQCDLEI-MEIKQLQQELQ-------DYQNKLIYLVPEKQLLNERIKNMQLGN---------------- 608
Cdd:TIGR00618  613 EQHALLRKLQPEQDLQDVrLHLQQCSQELAlkltalhALQLTLTQERVREHALSIRVLPKELLAsrqlalqkmqsekeql 692

                          250       260       270       280       290       300       310       320
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1804876928  609 TPDLG----IDLLHKKSLEKEELCQRLKEQLDALEKETASKLSEMDSFNNQL--KCGNMDDSVLQCLLSLLSCLNNLFLL 682
Cdd:TIGR00618  693 TYWKEmlaqCQTLLRELETHIEEYDREFNEIENASSSLGSDLAAREDALNQSlkELMHQARTVLKARTEAHFNNNEEVTA 772

                          330       340       350       360       370       380       390       400
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1804876928  683 -------LKELRESYNTQQLALEQLHKIKRDKLKEIERKRSELIQKKKLEDEAIRKAKQGKENLWRES----------LR 745
Cdd:TIGR00618  773 alqtgaeLSHLAAEIQFFNRLREEDTHLLKTLEAEIGQEIPSDEDILNLQCETLVQEEEQFLSRLEEKsatlgeithqLL 852

                          410       420
                   ....*....|....*....|....*..
gi 1804876928  746 KEEEEKQKRLQEEKTQEKVQEEERKVE 772
Cdd:TIGR00618  853 KYEECSKQLAQLTQEQAKIIQLSDKLN 879

Coiled-coil domain-containing protein 3; This family is found in eukaryotes; it has several conserved tryptophan residues. The function is not known.

Pssm-ID: 464032 [Multi-domain] Cd Length: 221 Bit Score: 47.78 E-value: 2.07e-05

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1804876928  416 KRRQALMEQQQREAERKAQKEKEEWERKQRELQE--QEW---KKQLELEKRLEKQRELERQREEERRKEIERREAA---- 486
Cdd:pfam13904   62 AAKQRQRQKELQAQKEEREKEEQEAELRKRLAKEkyQEWlqrKARQQTKKREESHKQKAAESASKSLAKPERKVSQeeak 141

                           90       100       110       120
                   ....*....|....*....|....*....|....*....|.
gi 1804876928  487 ---------KQELERQRRLEWER--IRRQELLNQRNREQEE 516
Cdd:pfam13904  142 evlqewerkKLEQQQRKREEEQReqLKKEEEEQERKQLAEK 182

Src Homology 3 domain of Membrane Protein, Palmitoylated 6 (or MAGUK p55 subfamily member 6); MPP6, also called Veli-associated MAGUK 1 (VAM-1) or PALS2, is a scaffolding protein that binds to Veli-1, a homolog of Caenorhabditis Lin-7. It is one of seven vertebrate homologs of the Drosophila Stardust protein, which is required in establishing cell polarity, and it contains two L27 domains followed by the core of three domains characteristic of MAGUK (membrane-associated guanylate kinase) proteins: PDZ, SH3, and guanylate kinase (GuK). In addition, it also contains the Hook (Protein 4.1 Binding) motif in between the SH3 and GuK domains. The GuK domain in MAGUK proteins is enzymatically inactive; instead, the domain mediates protein-protein interactions and associates intramolecularly with the SH3 domain. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212971 Cd Length: 61 Bit Score: 43.90 E-value: 2.10e-05

                           10        20        30        40
                   ....*....|....*....|....*....|....*....|..
gi 1804876928 1164 EDELNFSKGQLINVLNKDDPDWWQG---EINGVTGLFPSNYV 1202
Cdd:cd12038     20 EAGLKFSKGEILQIVNREDPNWWQAshvKEGGSAGLIPSQFL 61

Src homology 3 domain of Src-Like Adaptor Proteins; SLAPs are adaptor proteins with limited similarity to Src family tyrosine kinases. They contain an N-terminal SH3 domain followed by an SH2 domain, and a unique C-terminal sequence. They function in regulating the signaling, ubiquitination, and trafficking of T-cell receptor (TCR) and B-cell receptor (BCR) components. Vertebrates contain two SLAPs, named SLAP (or SLA1) and SLAP2 (or SLA2). SLAP has been shown to interact with the EphA receptor, EpoR, Lck, PDGFR, Syk, CD79a, among others, while SLAP2 interacts with CSF1R. Both SLAPs interact with c-Cbl, LAT, CD247, and Zap70. SLAP modulates TCR surface expression levels as well as surface and total BCR levels. As an adaptor to c-Cbl, SLAP increases the ubiquitination, intracellular retention, and targeted degradation of the BCR complex components. SLAP2 plays a role in c-Cbl-dependent regulation of CSF1R, a tyrosine kinase important for myeloid cell growth and differentiation. The SH3 domain of SLAP forms a complex with v-Abl. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212782 Cd Length: 55 Bit Score: 43.72 E-value: 2.11e-05

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|
gi 1804876928 1008 IALYSYSSVEPGDLTFIEGEEILVTQKDGEWWT--GSIGDRTGIFPSNYV 1055
Cdd:cd11848      3 VALGDYPSGGPAELSLRLGEPLTIVSDEGDWWKvlSEVTGRESYIPSVHV 52

Second Src homology 3 domain (or SH3B) of Intersectin-1; Intersectin-1 (ITSN1) is an adaptor protein that functions in exo- and endocytosis, actin cytoskeletal reorganization, and signal transduction. It plays a role in clathrin-coated pit (CCP) formation. It binds to many proteins through its multidomain structure and facilitate the assembly of multimeric complexes. ITSN1 localizes in membranous organelles, CCPs, the Golgi complex, and may be involved in the cell membrane trafficking system. It exists in alternatively spliced short and long isoforms. The short isoform contains two Eps15 homology domains (EH1 and EH2), a coiled-coil region and five SH3 domains (SH3A-E), while the long isoform, in addition, contains RhoGEF (also called Dbl-homologous or DH), Pleckstrin homology (PH) and C2 domains. The second SH3 domain (or SH3B) of ITSN1 has been shown to bind WNK and CdGAP. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212922 [Multi-domain] Cd Length: 52 Bit Score: 43.55 E-value: 2.15e-05

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|..
gi 1804876928  786 KALYRFEARSHDEMSFNSGDIIQVDEKtigEPGWLYGSFQGNFGWFPCNYVE 837
Cdd:cd11989      3 QALYPWRAKKDNHLNFNKNDVITVLEQ---QDMWWFGEVQGQKGWFPKSYVK 51

Second Src Homology 3 domain of FCH and double SH3 domains protein 1; FCHSD1 has a domain structure consisting of an N-terminal F-BAR (FES-CIP4 Homology and Bin/Amphiphysin/Rvs), two SH3, and C-terminal proline-rich domains. It has only been characterized in silico and its function is unknown. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212828 Cd Length: 58 Bit Score: 43.80 E-value: 2.20e-05

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|...
gi 1804876928 1009 ALYSYSSVEPGDLTFIEGEEILVTQK-----DGEWWTGSIGDRTGIFPSNYVK 1056
Cdd:cd11895      4 ALYSYTGQSPEELSFPEGALIRLLPRaqdgvDDGFWRGEFGGRVGVFPSLLVE 56

Fourth Src homology 3 domain (or SH3D) of Intersectin; Intersectins (ITSNs) are adaptor proteins that function in exo- and endocytosis, actin cytoskeletal reorganization, and signal transduction. They are essential for initiating clathrin-coated pit formation. They bind to many proteins through their multidomain structure and facilitate the assembly of multimeric complexes. Vertebrates contain two ITSN proteins, ITSN1 and ITSN2, which exist in alternatively spliced short and long isoforms. The short isoforms contain two Eps15 homology domains (EH1 and EH2), a coiled-coil region and five SH3 domains (SH3A-E), while the long isoforms, in addition, contain RhoGEF (also called Dbl-homologous or DH), Pleckstrin homology (PH) and C2 domains. ITSN1 and ITSN2 are both widely expressed, with variations depending on tissue type and stage of development. The fourth SH3 domain (or SH3D) of ITSN1 has been shown to bind SHIP2, Numb, CdGAP, and N-WASP. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212773 [Multi-domain] Cd Length: 58 Bit Score: 43.48 E-value: 2.21e-05

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|...
gi 1804876928  791 FEARSHDEMSFNSGDIIQVDEKTigEPGWLYGSFQGN-----FGWFPCNYVEK 838
Cdd:cd11839      8 FTATAENQLSLAVGQLVLVRKKS--PSGWWEGELQARgkkrqIGWFPANYVKL 58

Atrophin-1 family; Atrophin-1 is the protein product of the dentatorubral-pallidoluysian atrophy (DRPLA) gene. DRPLA OMIM:125370 is a progressive neurodegenerative disorder. It is caused by the expansion of a CAG repeat in the DRPLA gene on chromosome 12p. This results in an extended polyglutamine region in atrophin-1, that is thought to confer toxicity to the protein, possibly through altering its interactions with other proteins. The expansion of a CAG repeat is also the underlying defect in six other neurodegenerative disorders, including Huntington's disease. One interaction of expanded polyglutamine repeats that is thought to be pathogenic is that with the short glutamine repeat in the transcriptional coactivator CREB binding protein, CBP. This interaction draws CBP away from its usual nuclear location to the expanded polyglutamine repeat protein aggregates that are characteriztic of the polyglutamine neurodegenerative disorders. This interferes with CBP-mediated transcription and causes cytotoxicity.

Pssm-ID: 460830 [Multi-domain] Cd Length: 991 Bit Score: 49.38 E-value: 2.21e-05

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1804876928  120 IKLKLQGQQLPVvlPPImkQPPMFSPLISARFGMGSMPNLSIPHSLPPVAPMAT-PLSSATSGTTLPPLMMPAplvpsvs 198
Cdd:pfam03154  415 LQLMPQSQQLPP--PPA--QPPVLTQSQSLPPPAASHPPTSGLHQVPSQSPFPQhPFVPGGPPPITPPSGPPT------- 483

                           90       100       110
                   ....*....|....*....|....*....|
gi 1804876928  199 tsSLPNGTAGLIQPLSIPYSSS-TLPHTSS 227
Cdd:pfam03154  484 --STSSAMPGIQPPSSASVSSSgPVPAAVS 511

Second C-terminal Src homology 3 domain of Rho guanine nucleotide exchange factor 37; ARHGEF37 contains a RhoGEF [or Dbl homology (DH)] domain followed by a Bin/Amphiphysin/Rvs (BAR) domain, and two C-terminal SH3 domains. Its specific function is unknown. Its domain architecture is similar to the C-terminal half of DNMBP or Tuba, a cdc42-specific GEF that provides a functional link between dynamin, Rho GTPase signaling, and actin dynamics, and plays an important role in regulating cell junction configuration. GEFs activate small GTPases by exchanging bound GDP for free GTP. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212874 Cd Length: 57 Bit Score: 43.75 E-value: 2.25e-05

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....*
gi 1804876928 1152 QVIAMYDYVANNEDELNFSKGQLINVLNKDD----PDWWQGEINGVTGLFPSNYV 1202
Cdd:cd11941      1 QVVAAYPFTARSKHEVSLQAGQPVTVLEPHDkkgsPEWSLVEVNGQRGYVPSSYL 55

Third N-terminal Src homology 3 domain of Dynamin Binding Protein, also called Tuba; DNMBP or Tuba is a cdc42-specific guanine nucleotide exchange factor (GEF) that contains four N-terminal SH3 domains, a central RhoGEF [or Dbl homology (DH)] domain followed by a Bin/Amphiphysin/Rvs (BAR) domain, and two C-terminal SH3 domains. It provides a functional link between dynamin and key regulatory proteins of the actin cytoskeleton. It plays an important role in regulating cell junction configuration. The four N-terminal SH3 domains of DNMBP binds the GTPase dynamin, which plays an important role in the fission of endocytic vesicles. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212730 Cd Length: 51 Bit Score: 43.50 E-value: 2.29e-05

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|.
gi 1804876928  923 KAQALCSWTAKKDNHLNFSKHDIITVLEQQENWWF-GEVHGGRGWFPKSYV 972
Cdd:cd11796      1 QARVLQDLSAQLDEELDLREGDVVTITGILDKGWFrGELNGRRGIFPEGFV 51

Src homology 3 domain of ARHGEF9-like Rho guanine nucleotide exchange factors; Members of this family contain a SH3 domain followed by RhoGEF (also called Dbl-homologous or DH) and Pleckstrin Homology (PH) domains. They include the Rho guanine nucleotide exchange factors ARHGEF9, ASEF (also called ARHGEF4), ASEF2, and similar proteins. GEFs activate small GTPases by exchanging bound GDP for free GTP. ARHGEF9 specifically activates Cdc42, while both ASEF and ASEF2 can activate Rac1 and Cdc42. ARHGEF9 is highly expressed in the brain and it interacts with gephyrin, a postsynaptic protein associated with GABA and glycine receptors. ASEF plays a role in angiogenesis and cell migration. ASEF2 is important in cell migration and adhesion dynamics. ASEF exists in an autoinhibited form and is activated upon binding of the tumor suppressor APC (adenomatous polyposis coli), leading to the activation of Rac1 or Cdc42. In its autoinhibited form, the SH3 domain of ASEF forms an extensive interface with the DH and PH domains, blocking the Rac binding site. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212762 [Multi-domain] Cd Length: 53 Bit Score: 43.52 E-value: 2.30e-05

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|
gi 1804876928  787 ALYRFEARSHDEMSFNSGDIIQVDEKTigEPGWLYGSFQGNFGWFPCNYV 836
Cdd:cd11828      4 ALWDHVTMDPEELGFKAGDVIEVLDMS--DKDWWWGSIRDEEGWFPASFV 51

Second Src Homology 3 domain of Sorbin and SH3 domain containing 1 (Sorbs1), also called ponsin; Sorbs1 is also called ponsin, SH3P12, or CAP (c-Cbl associated protein). It is an adaptor protein containing one sorbin homology (SoHo) and three SH3 domains. It binds Cbl and plays a major role in regulating the insulin signaling pathway by enhancing insulin-induced phosphorylation of Cbl. Sorbs1, like vinexin, localizes at cell-ECM and cell-cell adhesion sites where it binds vinculin, paxillin, and afadin. It may function in the control of cell motility. Other interaction partners of Sorbs1 include c-Abl, Sos, flotillin, Grb4, ataxin-7, filamin C, among others. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212855 [Multi-domain] Cd Length: 58 Bit Score: 43.44 E-value: 2.34e-05

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....*
gi 1804876928 1152 QVIAMYDYVANNEDELNFSKGQLINVLNKDDPDWWQGEINGVT--GLFPSNYVKM 1204
Cdd:cd11922      2 EAIAKFNFNGDTQVEMSFRKGERITLLRQVDENWYEGRIPGTSrqGIFPITYVDV 56

PAT complex subunit CCDC47; This family represents CCDC47 proteins which are a component of the PAT complex, an endoplasmic reticulum (ER)-resident membrane multiprotein complex that facilitates multi-pass membrane proteins insertion into membranes. The PAT complex, formed by CCDC47 and Asterix proteins, acts as an intramembrane chaperone by directly interacting with nascent transmembrane domains (TMDs), releasing its substrates upon correct folding, and is needed for optimal biogenesis of multi-pass membrane proteins. CCDC47 is required to maintain the stability of Asterix. CCDC47 is associated with various membrane-associated processes and is component of a ribosome-associated ER translocon complex involved in multi-pass membrane protein transport into the ER membrane and biogenesis. It is also involved in the regulation of calcium ion homeostasis in the ER, being also required for proper protein degradation via the ERAD (ER-associated degradation) pathway.

Pssm-ID: 462322 Cd Length: 323 Bit Score: 48.33 E-value: 2.60e-05

                           10        20        30        40        50        60
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 1804876928  400 EDKRKANYERGNVELEKRRQALMEQQQREAERKAQKEKEEWERKQRELQEQEWKKQLELEKrlEKQ 465
Cdd:pfam07946  257 EALKKAKKTREEEIEKIKKAAEEERAEEAQEKKEEAKKKEREEKLAKLSPEEQRKYEEKER--KKE 320

Second Src Homology 3 domain of Vinexin, also called Sorbin and SH3 domain containing 3 (Sorbs3); Vinexin is also called Sorbs3, SH3P3, and SH3-containing adapter molecule 1 (SCAM-1). It is an adaptor protein containing one sorbin homology (SoHo) and three SH3 domains. Vinexin was first identified as a vinculin binding protein; it is co-localized with vinculin at cell-ECM and cell-cell adhesion sites. There are several splice variants of vinexin: alpha, which contains the SoHo and three SH3 domains and displays tissue-specific expression; and beta, which contains only the three SH3 domains and is widely expressed. Vinexin alpha stimulates the accumulation of F-actin at focal contact sites. Vinexin also promotes keratinocyte migration and wound healing. The SH3 domains of vinexin have been reported to bind a number of ligands including vinculin, WAVE2, DLG5, Abl, and Cbl. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212857 Cd Length: 56 Bit Score: 43.41 E-value: 2.62e-05

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....
gi 1804876928 1006 EYIALYSYSSVEPGDLTFIEGEEI-LVTQKDGEWWTGSIG--DRTGIFPSNYVK 1056
Cdd:cd11924      2 EAVAQYTFKGDLEVELSFRKGEHIcLIRKVNENWYEGRITgtGRQGIFPASYVQ 55

RIM-binding protein of the cytomatrix active zone; This is a family of proteins that form part of the CAZ (cytomatrix at the active zone) complex which is involved in determining the site of synaptic vesicle fusion. The C-terminus is a PDZ-binding motif that binds directly to RIM (a small G protein Rab-3A effector). The family also contains four coiled-coil domains.

Pssm-ID: 431111 [Multi-domain] Cd Length: 766 Bit Score: 49.05 E-value: 2.70e-05

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1804876928  520 LNSKKKSLHLELEA----LNGKHQQisgrLQDVRLRKQTQKTEIEVLDKQCDLEIMEIKQLQQELQDYQNKLiyLVPEKQ 595
Cdd:pfam10174  343 LQTEVDALRLRLEEkesfLNKKTKQ----LQDLTEEKSTLAGEIRDLKDMLDVKERKINVLQKKIENLQEQL--RDKDKQ 416

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1804876928  596 L--LNERIKNMQL-GNTPDLGIDLLHKKSLEKEELCQRLKEQLDALEKEtasKLSEMDSFNNQLKCGNMDDSVLQCLLSL 672
Cdd:pfam10174  417 LagLKERVKSLQTdSSNTDTALTTLEEALSEKERIIERLKEQREREDRE---RLEELESLKKENKDLKEKVSALQPELTE 493

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1804876928  673 LSCLnnlfllLKELREsyNTQQLALEQLHKIKRDKLKEIErkrselIQKKKleDEAIRKAKQGK--ENLWRESLRKEEEE 750
Cdd:pfam10174  494 KESS------LIDLKE--HASSLASSGLKKDSKLKSLEIA------VEQKK--EECSKLENQLKkaHNAEEAVRTNPEIN 557

                          250
                   ....*....|....*....
gi 1804876928  751 KQKRLQEEKTQEKVQEEER 769
Cdd:pfam10174  558 DRIRLLEQEVARYKEESGK 576

Third Src Homology 3 domain of SH3 domain containing ring finger 1, an E3 ubiquitin-protein ligase; SH3RF1 is also called POSH (Plenty of SH3s) or SH3MD2 (SH3 multiple domains protein 2). It is a scaffold protein that acts as an E3 ubiquitin-protein ligase. It plays a role in calcium homeostasis through the control of the ubiquitin domain protein Herp. It may also have a role in regulating death receptor mediated and JNK mediated apoptosis. SH3RF1 also enhances the ubiquitination of ROMK1 potassium channel resulting in its increased endocytosis. It contains an N-terminal RING finger domain and four SH3 domains. This model represents the third SH3 domain, located in the middle, of SH3RF1. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212859 [Multi-domain] Cd Length: 55 Bit Score: 43.42 E-value: 2.75e-05

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|.
gi 1804876928 1154 IAMYDYVANNEDELNFSKGQLINVLNKDDPDWWQGEI--NGVTGLFPSNYV 1202
Cdd:cd11926      3 VAIYPYTPRKEDELELRKGEMFLVFERCQDGWFKGTSmhTSKIGVFPGNYV 53

Src homology 3 domain of High osmolarity signaling protein Sho1p; Sho1p (or Sho1), also called SSU81 (Suppressor of SUA8-1 mutation), is a yeast membrane protein that regulates adaptation to high salt conditions by activating the HOG (high-osmolarity glycerol) pathway. High salt concentrations lead to the localization to the membrane of the MAPKK Pbs2, which is then activated by the MAPKK Ste11 and in turn, activates the MAPK Hog1. Pbs2 is localized to the membrane though the interaction of its PxxP motif with the SH3 domain of Sho1p. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212789 [Multi-domain] Cd Length: 55 Bit Score: 43.18 E-value: 2.78e-05

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|
gi 1804876928 1009 ALYSY--SSVEPGDLTFIEGEEILVTQKDGEWWTGSIGD-RTGIFPSNYV 1055
Cdd:cd11855      4 ALYPYdaSPDDPNELSFEKGEILEVSDTSGKWWQARKSNgETGICPSNYL 53

Domain of unknown function (DUF4670); This family of proteins is found in eukaryotes. Proteins in this family are typically between 373 and 763 amino acids in length.

Pssm-ID: 464815 [Multi-domain] Cd Length: 522 Bit Score: 48.79 E-value: 2.80e-05

                           10        20        30        40        50        60
                   ....*....|....*....|....*....|....*....|....*....|....*....|....
gi 1804876928  707 KLKEIERKRSELIQKKKLEDEAIRKAKQGKENLWRESLRKEEEEKQKRLQEEKTQEKVQEEERK 770
Cdd:pfam15709  346 RRLEVERKRREQEEQRRLQQEQLERAEKMREELELEQQRRFEEIRLRKQRLEEERQRQEEEERK 409

C-terminal Src Homology 3 domain of LIM and SH3 domain protein 1; Lasp1 is a cytoplasmic protein that binds focal adhesion proteins and is involved in cell signaling, migration, and proliferation. It is overexpressed in several cancer cells including breast, ovarian, bladder, and liver. In cancer cells, it can be found in the nucleus; its degree of nuclear localization correlates with tumor size and poor prognosis. Lasp1 is a 36kD protein containing an N-terminal LIM domain, two nebulin repeats, and a C-terminal SH3 domain. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212867 [Multi-domain] Cd Length: 59 Bit Score: 43.45 E-value: 2.85e-05

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....*..
gi 1804876928 1004 GDEYIALYSYSSVEPGDLTFIEGEEIL-VTQKDGEWWTGSI---GDrTGIFPSNYVK 1056
Cdd:cd11934      2 GKRYRAVYDYNAADEDEVSFQDGDTIVnVQQIDDGWMYGTVertGD-TGMLPANYVE 57

Src Homology 3 (SH3) domain of Apoptosis Stimulating of p53 protein 2; ASPP2 is the full length form of the previously-identified tumor supressor, p53-binding protein 2 (p53BP2). ASPP2 activates the apoptotic function of the p53 family of tumor suppressors (p53, p63, and p73). It plays a central role in regulating apoptosis and cell growth; ASPP2-deficient mice show postnatal death. Downregulated expression of ASPP2 is frequently found in breast tumors, lung cancer, and diffuse large B-cell lymphoma where it is correlated with a poor clinical outcome. ASPP2 contains a proline-rich region, four ankyrin (ANK) repeats, and an SH3 domain at its C-terminal half. The SH3 domain and the ANK repeats of ASPP2 contribute to the p53 binding site; they bind to the DNA binding domain of p53. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212886 [Multi-domain] Cd Length: 57 Bit Score: 43.40 E-value: 2.88e-05

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|.
gi 1804876928 1153 VIAMYDYVANNEDELNFSKGQLINVLNKDDPD---WWQGEINGVTGLFPSN 1200
Cdd:cd11953      3 VYALWDYEGESDDELSFKEGDCMTILRREDEDeteWWWARLNDKEGYVPRN 53

Src Homology 3 domain of fungal peroxisomal membrane protein Pex13p; Pex13p, located in the peroxisomal membrane, contains two transmembrane regions and a C-terminal SH3 domain. It binds to the peroxisomal targeting type I (PTS1) receptor Pex5p and the docking factor Pex14p through its SH3 domain. It is essential for both PTS1 and PTS2 protein import pathways into the peroxisomal matrix. Pex13p binds Pex14p, which contains a PxxP motif, in a classical fashion to the proline-rich ligand binding site of its SH3 domain. It binds the WxxxF/Y motif of Pex5p in a novel site that does not compete with Pex14p binding. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212705 [Multi-domain] Cd Length: 60 Bit Score: 43.42 E-value: 2.90e-05

                           10        20        30        40
                   ....*....|....*....|....*....|....*....|....*.
gi 1804876928  936 NHLNFSKHDIITVL------EQQENWWFGEVHGGR-GWFPKSYVKI 974
Cdd:cd11771     15 MELSLKKGDIVAVLsktdplGRDSEWWKGRTRDGRiGWFPSNYVEV 60

Src Homology 3 domain of alpha-Pak Interactive eXchange factor; Alpha-PIX, also called Rho guanine nucleotide exchange factor 6 (ARHGEF6) or Cool (Cloned out of Library)-2, activates small GTPases by exchanging bound GDP for free GTP. It acts as a GEF for both Cdc42 and Rac 1, and is localized in dendritic spines where it regulates spine morphogenesis. It controls dendritic length and spine density in the hippocampus. Mutations in the ARHGEF6 gene cause X-linked intellectual disability in humans. PIX proteins contain an N-terminal SH3 domain followed by RhoGEF (also called Dbl-homologous or DH) and Pleckstrin Homology (PH) domains, and a C-terminal leucine-zipper domain for dimerization. The SH3 domain of PIX binds to an atypical PxxxPR motif in p21-activated kinases (PAKs) with high affinity. The binding of PAKs to PIX facilitate the localization of PAKs to focal complexes and also localizes PAKs to PIX targets Cdc43 and Rac, leading to the activation of PAKs. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212993 Cd Length: 58 Bit Score: 43.45 E-value: 2.91e-05

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|...
gi 1804876928  922 LKAQALCSWTAKKDNHLNFSKHDIITVLEQQEN-WWFGEVHGGRGWFPKSYVK 973
Cdd:cd12060      2 LVVKARFNFKQTNEDELSVCKGDIIYVTRVEEGgWWEGTLNGKTGWFPSNYVR 54

Src homology 3 domain of Proline-Serine-Threonine Phosphatase-Interacting Protein 1; PSTPIP1, also called CD2 Binding Protein 1 (CD2BP1), is mainly expressed in hematopoietic cells. It is a binding partner of the cell surface receptor CD2 and PTP-PEST, a tyrosine phosphatase which functions in cell motility and Rac1 regulation. It also plays a role in the activation of the Wiskott-Aldrich syndrome protein (WASP), which couples actin rearrangement and T cell activation. Mutations in the gene encoding PSTPIP1 cause the autoinflammatory disorder known as PAPA (pyogenic sterile arthritis, pyoderma gangrenosum, and acne) syndrome. PSTPIP1 contains an N-terminal F-BAR domain, PEST motifs, and a C-terminal SH3 domain. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212758 [Multi-domain] Cd Length: 53 Bit Score: 43.13 E-value: 2.92e-05

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....
gi 1804876928  785 YKALYRFEARSHDEMSFNSGDIIQVDEKtiGEPGWLYGSFQGNFGWFPCNYVEK 838
Cdd:cd11824      2 YSVLYDYTAQEDDELSISKGDVVAVIEK--GEDGWWTVERNGQKGLVPGTYLEK 53

chromosome segregation protein SMC, common bacterial type; SMC (structural maintenance of chromosomes) proteins bind DNA and act in organizing and segregating chromosomes for partition. SMC proteins are found in bacteria, archaea, and eukaryotes. This family represents the SMC protein of most bacteria. The smc gene is often associated with scpB (TIGR00281) and scpA genes, where scp stands for segregation and condensation protein. SMC was shown (in Caulobacter crescentus) to be induced early in S phase but present and bound to DNA throughout the cell cycle. [Cellular processes, Cell division, DNA metabolism, Chromosome-associated proteins]

Pssm-ID: 274008 [Multi-domain] Cd Length: 1179 Bit Score: 49.28 E-value: 2.97e-05

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1804876928  555 QKTEIEVLDKQCDLEIMEIKQLQQELQDYQNKLiylvpeKQLLNERIKNMQLGNTPDLGIDLLHKKSLEKEELCQRLKEQ 634
Cdd:TIGR02168  675 RRREIEELEEKIEELEEKIAELEKALAELRKEL------EELEEELEQLRKELEELSRQISALRKDLARLEAEVEQLEER 748

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1804876928  635 LDALEKETASKLSEMDSFNNQL------------KCGNMDDSVLQCLLSLLSCLNNLFLL---LKELRESYNTQQLALEQ 699
Cdd:TIGR02168  749 IAQLSKELTELEAEIEELEERLeeaeeelaeaeaEIEELEAQIEQLKEELKALREALDELraeLTLLNEEAANLRERLES 828

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1804876928  700 LHKIKRDKLKEIERKRSeliQKKKLEDEAIRKAKQgkenlwRESLRKEEEEKQKRLQEEKTQEKVQEEERKVEEKQCEPA 779
Cdd:TIGR02168  829 LERRIAATERRLEDLEE---QIEELSEDIESLAAE------IEELEELIEELESELEALLNERASLEEALALLRSELEEL 899


                   ....*
gi 1804876928  780 SALVN 784
Cdd:TIGR02168  900 SEELR 904

Src homology 3 domain of Phospholipase C (PLC) gamma 1; PLCgamma1 is widely expressed and is essential in growth and development. It is activated by the TrkA receptor tyrosine kinase and functions as a key regulator of cell differentiation. It is also the predominant PLCgamma in T cells and is required for T cell and NK cell function. PLCs catalyze the hydrolysis of phosphatidylinositol (4,5)-bisphosphate [PtdIns(4,5)P2] to produce Ins(1,4,5)P3 and diacylglycerol (DAG). Ins(1,4,5)P3 initiates the calcium signaling cascade while DAG functions as an activator of PKC. PLCgamma contains a Pleckstrin homology (PH) domain followed by an elongation factor (EF) domain, two catalytic regions of PLC domains that flank two tandem SH2 domains, followed by a SH3 domain and C2 domain. The SH3 domain of PLCgamma1 directly interacts with dynamin-1 and can serve as a guanine nucleotide exchange factor (GEF). It also interacts with Cbl, inhibiting its phosphorylation and activity. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212903 Cd Length: 60 Bit Score: 43.44 E-value: 3.12e-05

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|...
gi 1804876928  925 QALCSWTAKKDNHLNFSKHDIITVLEQQE-NWWFGEVHGGRG-WFPKSYVKII 975
Cdd:cd11970      7 KALFDYKAQREDELTFTKNAIIQNVEKQEgGWWRGDYGGKKQlWFPSNYVEEI 59

Fourth Src homology 3 domain of ADAM-binding protein Eve-1; Eve-1, also called SH3 domain-containing protein 19 (SH3D19) or EEN-binding protein (EBP), exists in multiple alternatively spliced isoforms. The longest isoform contains five SH3 domain in the C-terminal region and seven proline-rich motifs in the N-terminal region. It is abundantly expressed in skeletal muscle and heart, and may be involved in regulating the activity of ADAMs (A disintegrin and metalloproteases). Eve-1 interacts with EEN, an endophilin involved in endocytosis and may be the target of the MLL-EEN fusion protein that is implicated in leukemogenesis. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212751 [Multi-domain] Cd Length: 50 Bit Score: 42.85 E-value: 3.25e-05

                           10        20        30        40
                   ....*....|....*....|....*....|....*....|....*....
gi 1804876928  787 ALYRFEARSHDEMSFNSGDIIQVDEKTIGEpgWLYGSFQGNFGWFPCNY 835
Cdd:cd11817      4 ALYDFTGETEEDLSFQRGDRILVTEHLDAE--WSRGRLNGREGIFPRAF 50

First Src homology 3 domain of Tyrosine kinase substrate with five SH3 domains; Tks5, also called SH3 and PX domain-containing protein 2A (SH3PXD2A) or Five SH (FISH), is a scaffolding protein and Src substrate that is localized in podosomes, which are electron-dense structures found in Src-transformed fibroblasts, osteoclasts, macrophages, and some invasive cancer cells. It binds and regulates some members of the ADAMs family of transmembrane metalloproteases, which function as sheddases and mediators of cell and matrix interactions. It is required for podosome formation, degradation of the extracellular matrix, and cancer cell invasion. Tks5 contains an N-terminal Phox homology (PX) domain and five SH3 domains. This model characterizes the first SH3 domain of Tks5. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 213007 [Multi-domain] Cd Length: 53 Bit Score: 43.16 E-value: 3.31e-05

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|...
gi 1804876928 1081 VTSAYVASGSEQLSLAPGQLILILKKNSSGWWqgelqARGKKRQKGWFPASHV 1133
Cdd:cd12074      4 VVSNYEKQENSEISLQAGEVVDVIEKNESGWW-----FVSTAEEQGWVPATYL 51

Src homology 3 domain of SH3 and multiple ankyrin repeat domains (Shank) proteins; Shank proteins carry scaffolding functions through multiple sites of protein-protein interaction in its domain architecture, including ankyrin (ANK) repeats, a long proline rich region, as well as SH3, PDZ, and SAM domains. They bind a variety of membrane and cytosolic proteins, and exist in alternatively spliced isoforms. They are highly enriched in postsynaptic density (PSD) where they interact with the cytoskeleton and with postsynaptic membrane receptors including NMDA and glutamate receptors. They are crucial in the construction and organization of the PSD and dendritic spines of excitatory synapses. There are three members of this family (Shank1, Shank2, Shank3) which show distinct and cell-type specific patterns of expression. Shank1 is brain-specific; Shank2 is found in neurons, glia, endocrine cells, liver, and kidney; Shank3 is widely expressed. The SH3 domain of Shank binds GRIP, a scaffold protein that binds AMPA receptors and Eph receptors/ligands. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212766 Cd Length: 50 Bit Score: 42.81 E-value: 3.32e-05

                           10        20        30        40
                   ....*....|....*....|....*....|....*....|....*...
gi 1804876928 1152 QVIAMYDYVANNEDELNFSKGQLINVLNKDDPDWWQGEINGVTGLFPS 1199
Cdd:cd11832      1 YFIAVKSYSPQEEGEISLHKGDRVKVLSIGEGGFWEGSVRGRTGWFPS 48

Trichohyalin-plectin-homology domain; This family is a mixtrue of two different families of eukaryotic proteins. Trichoplein or mitostatin, was first defined as a meiosis-specific nuclear structural protein. It has since been linked with mitochondrial movement. It is associated with the mitochondrial outer membrane, and over-expression leads to reduction in mitochondrial motility whereas lack of it enhances mitochondrial movement. The activity appears to be mediated through binding the mitochondria to the actin intermediate filaments (IFs). The family is in the trichohyalin-plectin-homology domain.

Pssm-ID: 464007 [Multi-domain] Cd Length: 341 Bit Score: 47.99 E-value: 3.32e-05

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1804876928  450 QEWKKQLElEKRLEKQRELERQREEERRKEIERREAAKQELERQRRLEWERIRRQELLnqrnREQEEIVRLNSKKKSLHL 529
Cdd:pfam13868   22 KERDAQIA-EKKRIKAEEKEEERRLDEMMEEERERALEEEEEKEEERKEERKRYRQEL----EEQIEEREQKRQEEYEEK 96

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1804876928  530 ELEALNGKHQQISGRLQDVRLRKQTQKTEIEVLD--KQCDLEIMEIKQLQQELQDYQNKLI--YLVpEKQLLNERIKNMQ 605
Cdd:pfam13868   97 LQEREQMDEIVERIQEEDQAEAEEKLEKQRQLREeiDEFNEEQAEWKELEKEEEREEDERIleYLK-EKAEREEEREAER 175

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1804876928  606 LgntpdlgidllhKKSLEKEELCQRLKEQLDALEKETAsklsEMDSFNNQLkcgnmddsvLQCLLSLLSCLNNLFLLLKE 685
Cdd:pfam13868  176 E------------EIEEEKEREIARLRAQQEKAQDEKA----ERDELRAKL---------YQEEQERKERQKEREEAEKK 230

                          250       260       270       280       290       300       310       320
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1804876928  686 LRESYNTQQLALEQLHKIKRDKLKEIERKRSELIQKKKLEDEAIRKAKQGKENlwRESLRKEEEEKQKRLQEEKTQEKVQ 765
Cdd:pfam13868  231 ARQRQELQQAREEQIELKERRLAEEAEREEEEFERMLRKQAEDEEIEQEEAEK--RRMKRLEHRRELEKQIEEREEQRAA 308

                          330
                   ....*....|
gi 1804876928  766 EEERKVEEKQ 775
Cdd:pfam13868  309 EREEELEEGE 318

Second Src Homology 3 domain of Sorbin and SH3 domain containing 2 (Sorbs2), also called Arg-binding protein 2 (ArgBP2); Sorbs2 or ArgBP2 is an adaptor protein containing one sorbin homology (SoHo) and three SH3 domains. It regulates actin-dependent processes including cell adhesion, morphology, and migration. It is expressed in many tissues and is abundant in the heart. Like vinexin, it is found in focal adhesion where it interacts with vinculin and afadin. It also localizes in epithelial cell stress fibers and in cardiac muscle cell Z-discs. Sorbs2 has been implicated to play roles in the signaling of c-Arg, Akt, and Pyk2. Other interaction partners of Sorbs2 include c-Abl, flotillin, spectrin, dynamin 1/2, synaptojanin, PTP-PEST, among others. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212856 [Multi-domain] Cd Length: 57 Bit Score: 42.98 E-value: 3.35e-05

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....*
gi 1804876928 1152 QVIAMYDYVANNEDELNFSKGQLINVLNKDDPDWWQGEINGVT--GLFPSNYVKM 1204
Cdd:cd11923      2 EAVAKYNFNADTNVELSLRKGDRVVLLKQVDQNWYEGKIPGTNrqGIFPVSYVEV 56

Src Homology 3 domain of Membrane Protein, Palmitoylated 7 (or MAGUK p55 subfamily member 7); MPP7 is a scaffolding protein that binds to DLG1 and promotes tight junction formation and epithelial cell polarity. Mutations in the MPP7 gene may be associated with the pathogenesis of diabetes and extreme bone mineral density. It is one of seven vertebrate homologs of the Drosophila Stardust protein, which is required in establishing cell polarity, and it contains two L27 domains followed by the core of three domains characteristic of MAGUK (membrane-associated guanylate kinase) proteins: PDZ, SH3, and guanylate kinase (GuK). The GuK domain in MAGUK proteins is enzymatically inactive; instead, the domain mediates protein-protein interactions and associates intramolecularly with the SH3 domain. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212966 Cd Length: 61 Bit Score: 43.09 E-value: 3.36e-05

                           10        20        30        40        50        60
                   ....*....|....*....|....*....|....*....|....*....|....*....|
gi 1804876928 1153 VIAMYDYVAN-------NEDELNFSKGQLINVLNKDDPDWWQ----GEINGVTGLFPSNY 1201
Cdd:cd12033      2 IKALFDYNPNedkaipcKEAGLSFKKGDILQIMSQDDATWWQakheGDANPRAGLIPSKH 61

Src homology 3 domain of Phospholipase C (PLC) gamma; PLC catalyzes the hydrolysis of phosphatidylinositol (4,5)-bisphosphate [PtdIns(4,5)P2] to produce Ins(1,4,5)P3 and diacylglycerol (DAG) in response to various receptors. Ins(1,4,5)P3 initiates the calcium signaling cascade while DAG functions as an activator of PKC. PLCgamma catalyzes this reaction in tyrosine kinase-dependent signaling pathways. It is activated and recruited to its substrate at the membrane. Vertebrates contain two forms of PLCgamma, PLCgamma1, which is widely expressed, and PLCgamma2, which is primarily found in haematopoietic cells. PLCgamma contains a Pleckstrin homology (PH) domain followed by an elongation factor (EF) domain, two catalytic regions of PLC domains that flank two tandem SH2 domains, followed by a SH3 domain and C2 domain. The SH3 domain of PLCgamma1 directly interacts with dynamin-1 and can serve as a guanine nucleotide exchange factor (GEF). It also interacts with Cbl, inhibiting its phosphorylation and activity. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212759 [Multi-domain] Cd Length: 54 Bit Score: 42.70 E-value: 3.61e-05

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|
gi 1804876928 1085 YVASGSEQLSLAPGQLILILKKNSSGWWQGELqarGKKRQKgWFPASHVK 1134
Cdd:cd11825      8 YRAQRPDELSFCKHAIITNVEKEDGGWWRGDY---GGKKQK-WFPANYVE 53

First C-terminal Src homology 3 domain of SH3 and cysteine-rich domain-containing (Stac) proteins; Stac proteins are putative adaptor proteins that contain a cysteine-rich C1 domain and one or two SH3 domains at the C-terminus. There are three mammalian members (Stac1, Stac2, and Stac3) of this family. Stac1 and Stac3 contain two SH3 domains while Stac2 contains a single SH3 domain at the C-terminus. This model represents the first C-terminal SH3 domain of Stac1 and Stac3, and the single C-terminal SH3 domain of Stac2. Stac1 and Stac2 have been found to be expressed differently in mature dorsal root ganglia (DRG) neurons. Stac1 is mainly expressed in peptidergic neurons while Stac2 is found in a subset of nonpeptidergic and all trkB+ neurons. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212767 [Multi-domain] Cd Length: 53 Bit Score: 42.87 E-value: 3.63e-05

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....
gi 1804876928  785 YKALYRFEARSHDEMSFNSGDIIQVDEKTIGEpgWLYGSFQGNFGWFPCNYVEK 838
Cdd:cd11833      2 YVALYKFKPQENEDLEMRPGDKITLLDDSNED--WWKGKIEDRVGFFPANFVQR 53

Second Src Homology 3 domain of Nck2 adaptor protein; Nck2 (also called Nckbeta or Growth factor receptor-bound protein 4, Grb4) plays a crucial role in connecting signaling pathways of tyrosine kinase receptors and important effectors in actin dynamics and cytoskeletal remodeling. It binds neuronal signaling proteins such as ephrinB and Disabled-1 (Dab-1) exclusively. Nck adaptor proteins regulate actin cytoskeleton dynamics by linking proline-rich effector molecules to protein tyrosine kinases and phosphorylated signaling intermediates. They contain three SH3 domains and a C-terminal SH2 domain. They function downstream of the PDGFbeta receptor and are involved in Rho GTPase signaling and actin dynamics. Vertebrates contain two Nck adaptor proteins: Nck1 (also called Nckalpha) and Nck2, which show partly overlapping functions but also bind distinct targets. The second SH3 domain of Nck appears to prefer ligands containing the APxxPxR motif. SH3 domains are protein interaction domains that usually bind to proline-rich ligands with moderate affinity and selectivity, preferentially a PxxP motif. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212835 [Multi-domain] Cd Length: 55 Bit Score: 43.07 E-value: 3.75e-05

                           10        20        30        40
                   ....*....|....*....|....*....|....*....|....*...
gi 1804876928  789 YRFEARSHDEMSFNSGDIIQVDEKTigEPGWLYGSFQGNFGWFPCNYV 836
Cdd:cd11902      7 FAYVAEREDELSLVKGSRVTVMEKC--SDGWWRGSYNGQIGWFPSNYV 52

N-terminal Src homology 3 domain of Growth factor receptor-bound protein 2; GRB2 is a critical signaling molecule that regulates the Ras pathway by linking tyrosine kinases to the Ras guanine nucleotide releasing protein Sos (son of sevenless), which converts Ras to the active GTP-bound state. It is ubiquitously expressed in all tissues throughout development and is important in cell cycle progression, motility, morphogenesis, and angiogenesis. In lymphocytes, GRB2 is associated with antigen receptor signaling components. GRB2 contains an N-terminal SH3 domain, a central SH2 domain, and a C-terminal SH3 domain. Its N-terminal SH3 domain binds to Sos and Sos-derived proline-rich peptides. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212879 [Multi-domain] Cd Length: 56 Bit Score: 43.09 E-value: 3.76e-05

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....*
gi 1804876928  922 LKAQALCSWTAKKDNHLNFSKHDIITVL--EQQENWWFGEVHGGRGWFPKSYVKI 974
Cdd:cd11946      1 MEAIAKYDFKATADDELSFKRGDILKVLneECDQNWYKAELNGKDGFIPKNYIEM 55

Second Src homology 3 domain of Tyrosine kinase substrate with four SH3 domains; Tks4, also called SH3 and PX domain-containing protein 2B (SH3PXD2B) or HOFI, is a Src substrate and scaffolding protein that plays an important role in the formation of podosomes and invadopodia, the dynamic actin-rich structures that are related to cell migration and cancer cell invasion. It is required in the formation of functional podosomes, EGF-induced membrane ruffling, and lamellipodia generation. It plays an important role in cellular attachment and cell spreading. Tks4 is essential for the localization of MT1-MMP (membrane-type 1 matrix metalloproteinase) to invadopodia. It contains an N-terminal Phox homology (PX) domain and four SH3 domains. This model characterizes the second SH3 domain of Tks4. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 213009 [Multi-domain] Cd Length: 54 Bit Score: 42.71 E-value: 3.80e-05

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....
gi 1804876928 1081 VTSAYVASGSEQLSLAPGQLILILKKNSSGWWQGELQArgkkrQKGWFPASHVK 1134
Cdd:cd12076      5 VIYPYTARDQDEINLEKGAVVEVIQKNLEGWWKIRYQG-----KEGWAPASYLK 53

Src homology 3 domain of Protein kinase C and Casein kinase Substrate in Neurons 3 (PACSIN3); PACSIN 3 or Syndapin III (Synaptic dynamin-associated protein III) is expressed ubiquitously and regulates glucose uptake in adipocytes through its role in GLUT1 trafficking. It also modulates the subcellular localization and stimulus-specific function of the cation channel TRPV4. PACSINs act as regulators of cytoskeletal and membrane dynamics. Vetebrates harbor three isoforms with distinct expression patterns and specific functions. PACSINs contain an N-terminal F-BAR domain and a C-terminal SH3 domain. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212930 [Multi-domain] Cd Length: 56 Bit Score: 43.02 E-value: 3.82e-05

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....*..
gi 1804876928  783 VNYKALYRFEARSHDEMSFNSG-DIIQVDEKTigEPGWLYGSFQ-GNFGWFPCNYVE 837
Cdd:cd11997      2 VRVRALYDYTGQEADELSFKAGeELLKIGEED--EQGWCKGRLLsGRIGLYPANYVE 56

Third Src Homology 3 domain of SH3 domain containing ring finger 3, an E3 ubiquitin-protein ligase; SH3RF3 is also called POSH2 (Plenty of SH3s 2) or SH3MD4 (SH3 multiple domains protein 4). It is a scaffold protein with E3 ubiquitin-protein ligase activity. It was identified in the screen for interacting partners of p21-activated kinase 2 (PAK2). It may play a role in regulating JNK mediated apoptosis in certain conditions. It also interacts with GTP-loaded Rac1. SH3RF3 is highly homologous to SH3RF1; it also contains an N-terminal RING finger domain and four SH3 domains. This model represents the third SH3 domain, located in the middle, of SH3RF3. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212858 Cd Length: 57 Bit Score: 43.06 E-value: 3.82e-05

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|.
gi 1804876928 1154 IAMYDYVANNEDELNFSKGQLINVLNKDDPDWWQGEI--NGVTGLFPSNYV 1202
Cdd:cd11925      4 LALYAYKPQKNDELELRKGEMYRVIEKCQDGWFKGTSlrTGVSGVFPGNYV 54

Src Homology 3 domain of Membrane Protein, Palmitoylated 1 (or MAGUK p55 subfamily member 1)-like proteins; This subfamily includes MPP1, CASK (Calcium/calmodulin-dependent Serine protein Kinase), Caenorhabditis elegans lin-2, and similar proteins. MPP1 and CASK are scaffolding proteins from the MAGUK (membrane-associated guanylate kinase) protein family, which is characterized by the presence of a core of three domains: PDZ, SH3, and guanylate kinase (GuK). In addition, they also have the Hook (Protein 4.1 Binding) motif in between the SH3 and GuK domains. The GuK domain in MAGUK proteins is enzymatically inactive; instead, the domain mediates protein-protein interactions and associates intramolecularly with the SH3 domain. CASK and lin-2 also contain an N-terminal calmodulin-dependent kinase (CaMK)-like domain and two L27 domains. MPP1 is ubiquitously-expressed and plays roles in regulating neutrophil polarity, cell shape, hair cell development, and neural development and patterning of the retina. CASK is highly expressed in the mammalian nervous system and plays roles in synaptic protein targeting, neural development, and gene expression regulation. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212968 Cd Length: 62 Bit Score: 43.19 E-value: 3.83e-05

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....*...
gi 1804876928 1153 VIAMYDYVANNED-------ELNFSKGQLINVLNKDDPDWWQ----GEINGVTGLFPS 1199
Cdd:cd12035      2 VRAQFDYDPSKDDlipcqqaGIAFKTGDILQIISKDDHNWWQarkpGASKEPAGLIPS 59

Src Homology 3 domain of TXK, also called Resting lymphocyte kinase (Rlk); TXK is a cytoplasmic (or nonreceptor) tyr kinase containing Src homology protein interaction domains (SH3, SH2) N-terminal to the catalytic tyr kinase domain. It also contains an N-terminal cysteine-rich region. Rlk is expressed in T-cells and mast cell lines, and is a key component of T-cell receptor (TCR) signaling. It is important in TCR-stimulated proliferation, IL-2 production and phospholipase C-gamma1 activation. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212840 [Multi-domain] Cd Length: 55 Bit Score: 43.02 E-value: 3.85e-05

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|..
gi 1804876928 1008 IALYSYSSVEPGDLTFIEGEEILVTQK-DGEWWTGSigDR---TGIFPSNYV 1055
Cdd:cd11907      4 KALYDFLPREPSNLALKRAEEYLILEQyDPHWWKAR--DRygnEGLIPSNYV 53

Ezrin/radixin/moesin, alpha-helical domain; The ERM family consists of three closely-related proteins, ezrin, radixin and moesin. Ezrin was first identified as a constituent of microvilli, radixin as a barbed, end-capping actin-modulating protein from isolated junctional fractions, and moesin as a heparin binding protein. A tumour suppressor molecule responsible for neurofibromatosis type 2 (NF2) is highly similar to ERM proteins and has been designated merlin (moesin-ezrin-radixin-like protein). ERM molecules contain 3 domains, an N-terminal globular domain, an extended alpha-helical domain and a charged C-terminal domain (pfam00769). Ezrin, radixin and merlin also contain a polyproline linker region between the helical and C-terminal domains. The N-terminal domain is highly conserved and is also found in merlin, band 4.1 proteins and members of the band 4.1 superfamily, designated the FERM domain. ERM proteins crosslink actin filaments with plasma membranes. They co-localize with CD44 at actin filament plasma membrane interaction sites, associating with CD44 via their N-terminal domains and with actin filaments via their C-terminal domains. This is the alpha-helical domain, which is involved in intramolecular masking of protein-protein interaction sites, regulating the activity of this proteins.

Pssm-ID: 466641 [Multi-domain] Cd Length: 120 Bit Score: 44.91 E-value: 3.92e-05

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1804876928  412 VELEKRRQALMEQ-QQREAE-RKAQKEKEEWERKQRELQEQewKKQLELEK-RLEKQRELERQREEERRKEIERREAAKQ 488
Cdd:pfam20492    2 EEAEREKQELEERlKQYEEEtKKAQEELEESEETAEELEEE--RRQAEEEAeRLEQKRQEAEEEKERLEESAEMEAEEKE 79

                           90       100       110
                   ....*....|....*....|....*....|..
gi 1804876928  489 ELERQRRLEWERIRRQEllNQRNREQEEIVRL 520
Cdd:pfam20492   80 QLEAELAEAQEEIARLE--EEVERKEEEARRL 109

Src Homology 3 domain of Bbc1 and similar domains; This subfamily is composed of Saccharomyces cerevisiae Bbc1p, also called Mti1p (Myosin tail region-interacting protein), and similar proteins. Bbc1p interacts with and regulates type I myosins in yeast, Myo3p and Myo5p, which are involved in actin cytoskeletal reorganization. It also binds and inhibits Las17, a WASp family protein that functions as an activator of the Arp2/3 complex. Bbc1p contains an N-terminal SH3 domain. SH3 domains bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs; they play a role in the regulation of enzymes by intramolecular interactions, changing the subcellular localization of signal pathway components and mediate multiprotein complex assemblies.

Pssm-ID: 212820 [Multi-domain] Cd Length: 60 Bit Score: 42.72 E-value: 4.07e-05

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....*...
gi 1804876928  786 KALYRFEARSHDEMSFNSGDIIQVDEKTIGEpgWLYGSFQGNFG-----WFPCNYVEK 838
Cdd:cd11887      5 KALYPYESDHEDDLNFDVGQLITVTEEEDAD--WYFGEYVDSNGntkegIFPKNFVEV 60

Fourth Src homology 3 domain (or SH3D) of Intersectin; Intersectins (ITSNs) are adaptor proteins that function in exo- and endocytosis, actin cytoskeletal reorganization, and signal transduction. They are essential for initiating clathrin-coated pit formation. They bind to many proteins through their multidomain structure and facilitate the assembly of multimeric complexes. Vertebrates contain two ITSN proteins, ITSN1 and ITSN2, which exist in alternatively spliced short and long isoforms. The short isoforms contain two Eps15 homology domains (EH1 and EH2), a coiled-coil region and five SH3 domains (SH3A-E), while the long isoforms, in addition, contain RhoGEF (also called Dbl-homologous or DH), Pleckstrin homology (PH) and C2 domains. ITSN1 and ITSN2 are both widely expressed, with variations depending on tissue type and stage of development. The fourth SH3 domain (or SH3D) of ITSN1 has been shown to bind SHIP2, Numb, CdGAP, and N-WASP. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212773 [Multi-domain] Cd Length: 58 Bit Score: 42.71 E-value: 4.07e-05

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....*..
gi 1804876928  924 AQALCSWTAKKDNHLNFSKHDIITVLEQQEN-WWFGEVHG-GR----GWFPKSYVKI 974
Cdd:cd11839      2 AQVIAPFTATAENQLSLAVGQLVLVRKKSPSgWWEGELQArGKkrqiGWFPANYVKL 58

Third Src Homology 3 domain of Nck1 adaptor protein; Nck1 (also called Nckalpha) plays a crucial role in connecting signaling pathways of tyrosine kinase receptors and important effectors in actin dynamics and cytoskeletal remodeling. It binds and activates RasGAP, resulting in the downregulation of Ras. It is also involved in the signaling of endothilin-mediated inhibition of cell migration. Nck adaptor proteins regulate actin cytoskeleton dynamics by linking proline-rich effector molecules to protein tyrosine kinases and phosphorylated signaling intermediates. They contain three SH3 domains and a C-terminal SH2 domain. They function downstream of the PDGFbeta receptor and are involved in Rho GTPase signaling and actin dynamics. Vertebrates contain two Nck adaptor proteins: Nck1 (also called Nckalpha) and Nck2, which show partly overlapping functions but also bind distinct targets. The third SH3 domain of Nck appears to prefer ligands with a PxAPxR motif. SH3 domains are protein interaction domains that usually bind to proline-rich ligands with moderate affinity and selectivity, preferentially a PxxP motif. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212837 [Multi-domain] Cd Length: 57 Bit Score: 42.71 E-value: 4.08e-05

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....
gi 1804876928  925 QALCSWTAKKDNHLNFSKHDIITVLEQQEN---WW-FGEVHGGRGWFPKSYVKI 974
Cdd:cd11904      4 QALYPFSSSNDEELNFEKGEVMDVIEKPENdpeWWkCRKANGQVGLVPKNYVTV 57

Src homology 3 domain of Abl Interactor proteins; Abl interactor (Abi) proteins are adaptor proteins serving as binding partners and substrates of Abl tyrosine kinases. They are involved in regulating actin cytoskeletal reorganization and play important roles in membrane-ruffling, endocytosis, cell motility, and cell migration. They localize to sites of actin polymerization in epithelial adherens junction and immune synapses, as well as to the leading edge of lamellipodia. Vertebrates contain two Abi proteins, Abi1 and Abi2. Abi1 displays a wide expression pattern while Abi2 is highly expressed in the eye and brain. Abi proteins contain a homeobox homology domain, a proline-rich region, and a SH3 domain. The SH3 domain of Abi binds to a PxxP motif in Abl. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212760 [Multi-domain] Cd Length: 52 Bit Score: 42.69 E-value: 4.13e-05

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|
gi 1804876928 1084 AYVASGSEQLSLAPGQLILILKKNSSGWWQGELQARgkkrqKGWFPASHV 1133
Cdd:cd11826      7 DYTADKDDELSFQEGDIIYVTKKNDDGWYEGVLNGV-----TGLFPGNYV 51

Src homology 3 domain of Ubiquitin-associated and SH3 domain-containing proteins, also called TULA (T cell Ubiquitin LigAnd) family of proteins; UBASH3 or TULA proteins are also referred to as Suppressor of T cell receptor Signaling (STS) proteins. They contain an N-terminal UBA domain, a central SH3 domain, and a C-terminal histidine phosphatase domain. They bind c-Cbl through the SH3 domain and to ubiquitin via UBA. In some vertebrates, there are two TULA family proteins, called UBASH3A (also called TULA or STS-2) and UBASH3B (also called TULA-2 or STS-1), which show partly overlapping as well as distinct functions. UBASH3B is widely expressed while UBASH3A is only found in lymphoid cells. UBASH3A facilitates apoptosis induced in T cells through its interaction with the apoptosis-inducing factor AIF. UBASH3B is an active phosphatase while UBASH3A is not. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212725 [Multi-domain] Cd Length: 59 Bit Score: 42.67 E-value: 4.24e-05

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....*....
gi 1804876928 1150 VCQVIamYDYVANNEDELNFSKGQLINV----LNKDDPDWWQG--EINGVTGLFPSNYV 1202
Cdd:cd11791      1 VLRVL--YPYTPQEEDELELVPGDYIYVspeeLDSSSDGWVEGtsWLTGCSGLLPENYT 57

N-terminal Src homology 3 domain of GRB2-related adaptor protein; GRAP is a GRB-2 like adaptor protein that is highly expressed in lymphoid tissues. It acts as a negative regulator of T cell receptor (TCR)-induced lymphocyte proliferation by downregulating the signaling to the Ras/ERK pathway. It has been identified as a regulator of TGFbeta signaling in diabetic kidney tubules and may have a role in the pathogenesis of the disease. GRAP contains an N-terminal SH3 domain, a central SH2 domain, and a C-terminal SH3 domain. The N-terminal SH3 domain of the related protein GRB2 binds to Sos and Sos-derived proline-rich peptides. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212881 [Multi-domain] Cd Length: 54 Bit Score: 42.50 E-value: 4.25e-05

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|...
gi 1804876928 1006 EYIALYSYSSVEPGDLTFIEGEEILVT--QKDGEWWTGSIGDRTGIFPSNYVK 1056
Cdd:cd11948      1 EAVALYSFQATESDELPFQKGDILKILnmEDDQNWYKAELQGREGYIPKNYIK 53

Src homology 3 domain of Abl Interactor 2; Abi2 is highly expressed in the brain and eye. It regulates actin cytoskeletal reorganization at adherens junctions and dendritic spines, which is important in cell morphogenesis, migration, and cognitive function. Mice deficient with Abi2 show defects in orientation and migration of lens fibers, neuronal migration, dendritic spine morphology, as well as deficits in learning and memory. Abi proteins are adaptor proteins serving as binding partners and substrates of Abl tyrosine kinases. They are involved in regulating actin cytoskeletal reorganization and play important roles in membrane-ruffling, endocytosis, cell motility, and cell migration. Abi proteins contain a homeobox homology domain, a proline-rich region, and a SH3 domain. The SH3 domain of Abi binds to a PxxP motif in Abl. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212905 [Multi-domain] Cd Length: 61 Bit Score: 43.07 E-value: 4.28e-05

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|...
gi 1804876928 1005 DEYIALYSYSSVEPGDLTFIEGEEILVTQK-DGEWWTGSIGDRTGIFPSNYVK 1056
Cdd:cd11972      3 EKVVAIYDYTKDKEDELSFQEGAIIYVIKKnDDGWYEGVMNGVTGLFPGNYVE 55

phosphodiesterase; Provisional

Pssm-ID: 237177 [Multi-domain] Cd Length: 520 Bit Score: 48.24 E-value: 4.29e-05

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1804876928  418 RQALMEQQQREAERKAQKEKEEwerKQRELQEQewKKQLELEkrlekqrelerqreeerrkeierreaAKQELERQRRlE 497
Cdd:PRK12704    25 RKKIAEAKIKEAEEEAKRILEE---AKKEAEAI--KKEALLE--------------------------AKEEIHKLRN-E 72

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1804876928  498 WE---RIRRQELLNQRNREQEEIVRLNSKKKSLHLELEALNGKHQQISGRLQDVrlrkQTQKTEIEVLDKQCDLEIMEIK 574
Cdd:PRK12704    73 FEkelRERRNELQKLEKRLLQKEENLDRKLELLEKREEELEKKEKELEQKQQEL----EKKEEELEELIEEQLQELERIS 148


                   ....*
gi 1804876928  575 QLQQE 579
Cdd:PRK12704   149 GLTAE 153

C-terminal Src homology 3 domain of GRB2-related adaptor protein; GRAP is a GRB-2 like adaptor protein that is highly expressed in lymphoid tissues. It acts as a negative regulator of T cell receptor (TCR)-induced lymphocyte proliferation by downregulating the signaling to the Ras/ERK pathway. It has been identified as a regulator of TGFbeta signaling in diabetic kidney tubules and may have a role in the pathogenesis of the disease. GRAP contains an N-terminal SH3 domain, a central SH2 domain, and a C-terminal SH3 domain. The C-terminal SH3 domains (SH3c) of the related proteins, GRB2 and GRAP2, have been shown to bind to classical PxxP motif ligands, as well as to non-classical motifs. GRB2 SH3c binds Gab2 (Grb2-associated binder 2) through epitopes containing RxxK motifs, while the SH3c of GRAP2 binds to the phosphatase-like protein HD-PTP via a RxxxxK motif. SH3 domains are protein interaction domains that typically bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212884 Cd Length: 53 Bit Score: 42.48 E-value: 4.35e-05

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|.
gi 1804876928  786 KALYRFEARSHDEMSFNSGDIIQVDEKTigEPGWLYGSFQGNFGWFPCNYV 836
Cdd:cd11951      3 QAQYDFSAEDPSQLSFRRGDIIEVLDCP--DPNWWRGRISGRVGFFPRNYV 51

Second Src homology 3 domain of Tyrosine kinase substrate with five SH3 domains; Tks5, also called SH3 and PX domain-containing protein 2A (SH3PXD2A) or Five SH (FISH), is a scaffolding protein and Src substrate that is localized in podosomes, which are electron-dense structures found in Src-transformed fibroblasts, osteoclasts, macrophages, and some invasive cancer cells. It binds and regulates some members of the ADAMs family of transmembrane metalloproteases, which function as sheddases and mediators of cell and matrix interactions. It is required for podosome formation, degradation of the extracellular matrix, and cancer cell invasion. Tks5 contains an N-terminal Phox homology (PX) domain and five SH3 domains. This model characterizes the second SH3 domain of Tks5. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 213010 Cd Length: 54 Bit Score: 42.71 E-value: 4.41e-05

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....
gi 1804876928  785 YKALYRFEARSHDEMSFNSGDIIQVDEKTIgePGWLYGSFQGNFGWFPCNYVEK 838
Cdd:cd12077      3 YVTVQPYTSQGKDEIGFEKGVTVEVIQKNL--EGWWYIRYLGKEGWAPASYLKK 54

Src Homology 3 domain of Myosin XV; This subfamily is composed of proteins with similarity to Myosin XVa. Myosin XVa is an unconventional myosin that is critical for the normal growth of mechanosensory stereocilia of inner ear hair cells. Mutations in the myosin XVa gene are associated with nonsyndromic hearing loss. Myosin XVa contains a unique N-terminal extension followed by a motor domain, light chain-binding IQ motifs, and a tail consisting of a pair of MyTH4-FERM tandems separated by a SH3 domain, and a PDZ domain. SH3 domains bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs; they play a role in the regulation of enzymes by intramolecular interactions, changing the subcellular localization of signal pathway components and mediate multiprotein complex assemblies.

Pssm-ID: 212817 [Multi-domain] Cd Length: 56 Bit Score: 42.70 E-value: 4.60e-05

                           10        20        30
                   ....*....|....*....|....*....|....*....
gi 1804876928  938 LNFSKHDIITVL----EQQENWWFGEVHGGRGWFPKSYV 972
Cdd:cd11884     16 LSFHKGDVIKLLpkegPLDPGWLFGTLDGRSGAFPKEYV 54

Src Homology 3 domain of Membrane Protein, Palmitoylated 5 (or MAGUK p55 subfamily member 5); MPP5, also called PALS1 (Protein associated with Lin7) or Nagie oko protein in zebrafish or Stardust in Drosophila, is a scaffolding protein which associates with Crumbs homolog 1 (CRB1), CRB2, or CRB3 through its PDZ domain and with PALS1-associated tight junction protein (PATJ) or multi-PDZ domain protein 1 (MUPP1) through its L27 domain. The resulting tri-protein complexes are core proteins of the Crumb complex, which localizes at tight junctions or subapical regions, and is involved in the maintenance of apical-basal polarity in epithelial cells and the morphogenesis and function of photoreceptor cells. MPP5 is critical for the proper stratification of the retina and is also expressed in T lymphocytes where it is important for TCR-mediated activation of NFkB. Drosophila Stardust exists in several isoforms, some of which show opposing functions in photoreceptor cells, which suggests that the relative ratio of different Crumbs complexes regulates photoreceptor homeostasis. MPP5 contains two L27 domains followed by the core of three domains characteristic of MAGUK (membrane-associated guanylate kinase) proteins: PDZ, SH3, and guanylate kinase (GuK). In addition, it also contains the Hook (Protein 4.1 Binding) motif in between the SH3 and GuK domains. The GuK domain in MAGUK proteins is enzymatically inactive; instead, the domain mediates protein-protein interactions and associates intramolecularly with the SH3 domain. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212969 Cd Length: 63 Bit Score: 42.79 E-value: 4.62e-05

                           10        20        30        40
                   ....*....|....*....|....*....|....*....|....*..
gi 1804876928 1159 YVANNEDELNFSKGQLINVLNKDDPDWWQGEING------VTGLFPS 1199
Cdd:cd12036     15 YIPCRELGLSFQKGDILHVISQEDPNWWQAYREGeednqsLAGLIPS 61

Src homology 3 domain of Protein arginine N-methyltransferase 2; PRMT2, also called HRMT1L1, belongs to the arginine methyltransferase protein family. It functions as a coactivator to both estrogen receptor alpha (ER-alpha) and androgen receptor (AR), presumably through arginine methylation. The ER-alpha transcription factor is involved in cell proliferation, differentiation, morphogenesis, and apoptosis, and is also implicated in the development and progression of breast cancer. PRMT2 and its variants are upregulated in breast cancer cells and may be involved in modulating the ER-alpha signaling pathway during formation of breast cancer. PRMT2 also plays a role in regulating the function of E2F transcription factors, which are critical cell cycle regulators, by binding to the retinoblastoma gene product (RB). It contains an N-terminal SH3 domain and an AdoMet binding domain. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212740 [Multi-domain] Cd Length: 53 Bit Score: 42.38 E-value: 4.77e-05

                           10        20        30        40
                   ....*....|....*....|....*....|....*....|....*...
gi 1804876928  926 ALCSWTAKKDNHLNFSKHDIITVLEQ-QENWWFGEVHGGRGWFPKSYV 972
Cdd:cd11806      4 AIADFVATDDSQLSFESGDKLLVLRKpSVDWWWAEHNGCCGYIPASHL 51

Fifth Src homology 3 domain (or SH3E) of Intersectin; Intersectins (ITSNs) are adaptor proteins that function in exo- and endocytosis, actin cytoskeletal reorganization, and signal transduction. They are essential for initiating clathrin-coated pit formation. They bind to many proteins through their multidomain structure and facilitate the assembly of multimeric complexes. Vertebrates contain two ITSN proteins, ITSN1 and ITSN2, which exist in alternatively spliced short and long isoforms. The short isoforms contain two Eps15 homology domains (EH1 and EH2), a coiled-coil region and five SH3 domains (SH3A-E), while the long isoforms, in addition, contain RhoGEF (also called Dbl-homologous or DH), Pleckstrin homology (PH) and C2 domains. ITSN1 and ITSN2 are both widely expressed, with variations depending on tissue type and stage of development. The fifth SH3 domain (or SH3E) of ITSN1 has been shown to bind many protein partners including SGIP1, Sos1, dynamin1/2, CIN85, c-Cbl, SHIP2, N-WASP, and synaptojanin-1, among others. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212774 [Multi-domain] Cd Length: 53 Bit Score: 42.40 E-value: 4.78e-05

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|.
gi 1804876928 1085 YVASGSEQLSLAPGQLILILKKNSSGWWQGELQArgkkrQKGWFPASHVKL 1135
Cdd:cd11840      8 YTAQNEDELSFQKGDIINVLSKDDPDWWRGELNG-----QTGLFPSNYVEP 53

Src Homology 3 domain of Myosin XV; This subfamily is composed of proteins with similarity to Myosin XVa. Myosin XVa is an unconventional myosin that is critical for the normal growth of mechanosensory stereocilia of inner ear hair cells. Mutations in the myosin XVa gene are associated with nonsyndromic hearing loss. Myosin XVa contains a unique N-terminal extension followed by a motor domain, light chain-binding IQ motifs, and a tail consisting of a pair of MyTH4-FERM tandems separated by a SH3 domain, and a PDZ domain. SH3 domains bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs; they play a role in the regulation of enzymes by intramolecular interactions, changing the subcellular localization of signal pathway components and mediate multiprotein complex assemblies.

Pssm-ID: 212817 [Multi-domain] Cd Length: 56 Bit Score: 42.70 E-value: 4.88e-05

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....
gi 1804876928 1008 IALYSYSSVEPGDLTFIEGEEILVTQKDGE----WWTGSIGDRTGIFPSNYVKP 1057
Cdd:cd11884      3 VAVRAYITRDQTLLSFHKGDVIKLLPKEGPldpgWLFGTLDGRSGAFPKEYVQP 56

Arginine and glutamate-rich 1; ARGLU, arginine and glutamate-rich 1 protein family, is required for the oestrogen-dependent expression of ESR1 target genes. It functions in cooperation with MED1. The family of proteins is found in eukaryotes.

Pssm-ID: 405931 [Multi-domain] Cd Length: 151 Bit Score: 45.43 E-value: 4.94e-05

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1804876928  698 EQLHKIKRDKLKEIERKRSELIQKKKLEDEAIRKAKQGKENLWR-------ESLRKEEEEKQKRLQEEKTQEKVQEEERK 770
Cdd:pfam15346   45 EARKIMEKQVLEELEREREAELEEERRKEEEERKKREELERILEennrkieEAQRKEAEERLAMLEEQRRMKEERQRREK 124


                   ....*
gi 1804876928  771 VEEKQ 775
Cdd:pfam15346  125 EEEER 129

Src homology 3 domain of Myosins Ie, If, and similar proteins; Myosins Ie (MyoIe) and If (MyoIf) are nonmuscle, unconventional, long tailed, class I myosins containing an N-terminal motor domain and a myosin tail with TH1, TH2, and SH3 domains. MyoIe interacts with the endocytic proteins, dynamin and synaptojanin-1, through its SH3 domain; it may play a role in clathrin-dependent endocytosis. In the kidney, MyoIe is critical for podocyte function and normal glomerular filtration. Mutations in MyoIe is associated with focal segmental glomerulosclerosis, a disease characterized by massive proteinuria and progression to end-stage kidney disease. MyoIf is predominantly expressed in the immune system; it plays a role in immune cell motility and innate immunity. Mutations in MyoIf may be associated with the loss of hearing. The MyoIf gene has also been found to be fused to the MLL (Mixed lineage leukemia) gene in infant acute myeloid leukemias (AML). SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212761 [Multi-domain] Cd Length: 53 Bit Score: 42.40 E-value: 4.97e-05

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gi 1804876928  923 KAQALCSWTAKKDNHLNFSKHDIITVL-EQQENWWFGEVHGGRGWFPKSYV 972
Cdd:cd11827      1 QCKALYAYDAQDTDELSFNEGDIIEILkEDPSGWWTGRLRGKEGLFPGNYV 51

Src Homology 3 domain of Brain-specific Angiogenesis Inhibitor 1-Associated Protein 2-Like 2; BAIAP2L2 co-localizes with clathrin plaques but its function has not been determined. It contains an N-terminal IMD or Inverse-Bin/Amphiphysin/Rvs (I-BAR) domain, an SH3 domain, and a WASP homology 2 (WH2) actin-binding motif at the C-terminus. The related proteins, BAIAP2L1 and IRSp53, function as regulators of membrane dynamics and the actin cytoskeleton. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212847 [Multi-domain] Cd Length: 59 Bit Score: 42.49 E-value: 4.99e-05

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gi 1804876928  799 MSFNSGDIIQVdekTIGEP--GWLYGSFQGNF--GWFPCNYVEKM 839
Cdd:cd11914     18 LRFNRGDIITV---LVPEArnGWLYGKLEGSSrqGWFPEAYVKAL 59

First Src homology 3 domain of Tyrosine kinase substrate with four SH3 domains; Tks4, also called SH3 and PX domain-containing protein 2B (SH3PXD2B) or HOFI, is a Src substrate and scaffolding protein that plays an important role in the formation of podosomes and invadopodia, the dynamic actin-rich structures that are related to cell migration and cancer cell invasion. It is required in the formation of functional podosomes, EGF-induced membrane ruffling, and lamellipodia generation. It plays an important role in cellular attachment and cell spreading. Tks4 is essential for the localization of MT1-MMP (membrane-type 1 matrix metalloproteinase) to invadopodia. It contains an N-terminal Phox homology (PX) domain and four SH3 domains. This model characterizes the first SH3 domain of Tks4. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 213008 Cd Length: 55 Bit Score: 42.37 E-value: 4.99e-05

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gi 1804876928 1081 VTSAYVASGSEQLSLAPGQLILILKKNSSGWWqgelqARGKKRQKGWFPAS 1131
Cdd:cd12075      5 VVANYQKQESSEISLYVGQVVDIIEKNESGWW-----FVSTADEQGWVPAT 50

Third Src Homology 3 domain (SH3C) of Cbl-interacting protein of 85 kDa; CIN85, also called SH3 domain-containing kinase-binding protein 1 (SH3KBP1) or CD2-binding protein 3 (CD2BP3) or Ruk, is an adaptor protein that is involved in the downregulation of receptor tyrosine kinases by facilitating endocytosis through interaction with endophilin-associated ubiquitin ligase Cbl proteins. It is also important in many other cellular processes including vesicle-mediated transport, cytoskeletal remodelling, apoptosis, cell adhesion and migration, and viral infection, among others. CIN85 exists as multiple variants from alternative splicing; the main variant contains three SH3 domains, a proline-rich region, and a C-terminal coiled-coil domain. All of these domains enable CIN85 to bind various protein partners and assemble complexes that have been implicated in many different functions. This alignment model represents the third SH3 domain (SH3C) of CIN85. SH3C has been shown to bind ubiquitin. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212990 [Multi-domain] Cd Length: 56 Bit Score: 42.58 E-value: 5.14e-05

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gi 1804876928  925 QALCSWTAKKDNHLNFSKHDIITVLEQQ---ENWWFGEVHGGRGWFPKSYVKII 975
Cdd:cd12057      3 KVLFPYEAQNEDELTIKEGDIVTLISKDcidAGWWEGELNGRRGVFPDNFVKLL 56

C-terminal (or second) Src homology 3 domain of VAV proteins; VAV proteins function both as cytoplasmic guanine nucleotide exchange factors (GEFs) for Rho GTPases and scaffold proteins and they play important roles in cell signaling by coupling cell surface receptors to various effector functions. They play key roles in processes that require cytoskeletal reorganization including immune synapse formation, phagocytosis, cell spreading, and platelet aggregation, among others. Vertebrates have three VAV proteins (VAV1, VAV2, and VAV3). VAV proteins contain several domains that enable their function: N-terminal calponin homology (CH), acidic, RhoGEF (also called Dbl-homologous or DH), Pleckstrin Homology (PH), C1 (zinc finger), SH2, and two SH3 domains. The SH3 domain of VAV is involved in the localization of proteins to specific sites within the cell, by interacting with proline-rich sequences within target proteins. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212764 [Multi-domain] Cd Length: 54 Bit Score: 42.62 E-value: 5.19e-05

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gi 1804876928 1078 IAQVTSAYVASGSEQLSLAPGQLILIL-KKNSSGWWQGELQARgkkrqKGWFPASHVK 1134
Cdd:cd11830      1 TAKARYDFCARDMRELSLKEGDVVKIYnKKGQQGWWRGEINGR-----IGWFPSTYVE 53

Third Src Homology 3 domain of Nck adaptor proteins; This group contains the third SH3 domain of Nck, the first SH3 domain of Caenorhabditis elegans Ced-2 (Cell death abnormality protein 2), and similar domains. Nck adaptor proteins regulate actin cytoskeleton dynamics by linking proline-rich effector molecules to protein tyrosine kinases and phosphorylated signaling intermediates. They contain three SH3 domains and a C-terminal SH2 domain. They function downstream of the PDGFbeta receptor and are involved in Rho GTPase signaling and actin dynamics. Vertebrates contain two Nck adaptor proteins: Nck1 (also called Nckalpha) and Nck2 (also called Nckbeta or Growth factor receptor-bound protein 4, Grb4), which show partly overlapping functions but also bind distinct targets. Their SH3 domains are involved in recruiting downstream effector molecules, such as the N-WASP/Arp2/3 complex, which when activated induces actin polymerization that results in the production of pedestals, or protrusions of the plasma membrane. The third SH3 domain of Nck appears to prefer ligands with a PxAPxR motif. SH3 domains are protein interaction domains that usually bind to proline-rich ligands with moderate affinity and selectivity, preferentially a PxxP motif. Ced-2 is a cell corpse engulfment protein that interacts with Ced-5 in a pathway that regulates the activation of Ced-10, a Rac small GTPase.

Pssm-ID: 212701 [Multi-domain] Cd Length: 56 Bit Score: 42.30 E-value: 5.33e-05

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gi 1804876928 1008 IALYSYSSVEPGDLTFIEGEEILVTQK---DGEWWTG--SIGDrTGIFPSNYVK 1056
Cdd:cd11767      3 VALYPFTGENDEELSFEKGERLEIIEKpedDPDWWKArnALGT-TGLVPRNYVE 55

Third Src Homology 3 domain (SH3C) of Cbl-interacting protein of 85 kDa; CIN85, also called SH3 domain-containing kinase-binding protein 1 (SH3KBP1) or CD2-binding protein 3 (CD2BP3) or Ruk, is an adaptor protein that is involved in the downregulation of receptor tyrosine kinases by facilitating endocytosis through interaction with endophilin-associated ubiquitin ligase Cbl proteins. It is also important in many other cellular processes including vesicle-mediated transport, cytoskeletal remodelling, apoptosis, cell adhesion and migration, and viral infection, among others. CIN85 exists as multiple variants from alternative splicing; the main variant contains three SH3 domains, a proline-rich region, and a C-terminal coiled-coil domain. All of these domains enable CIN85 to bind various protein partners and assemble complexes that have been implicated in many different functions. This alignment model represents the third SH3 domain (SH3C) of CIN85. SH3C has been shown to bind ubiquitin. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212990 [Multi-domain] Cd Length: 56 Bit Score: 42.58 E-value: 5.45e-05

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gi 1804876928 1080 QVTSAYVASGSEQLSLAPGQLILILKKN--SSGWWQGELQARgkkrqKGWFPASHVKLL 1136
Cdd:cd12057      3 KVLFPYEAQNEDELTIKEGDIVTLISKDciDAGWWEGELNGR-----RGVFPDNFVKLL 56

Src homology 3 domain of Ubiquitin-associated and SH3 domain-containing proteins, also called TULA (T cell Ubiquitin LigAnd) family of proteins; UBASH3 or TULA proteins are also referred to as Suppressor of T cell receptor Signaling (STS) proteins. They contain an N-terminal UBA domain, a central SH3 domain, and a C-terminal histidine phosphatase domain. They bind c-Cbl through the SH3 domain and to ubiquitin via UBA. In some vertebrates, there are two TULA family proteins, called UBASH3A (also called TULA or STS-2) and UBASH3B (also called TULA-2 or STS-1), which show partly overlapping as well as distinct functions. UBASH3B is widely expressed while UBASH3A is only found in lymphoid cells. UBASH3A facilitates apoptosis induced in T cells through its interaction with the apoptosis-inducing factor AIF. UBASH3B is an active phosphatase while UBASH3A is not. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212725 [Multi-domain] Cd Length: 59 Bit Score: 42.29 E-value: 5.59e-05

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gi 1804876928  785 YKALYRFEARSHDEMSFNSGDIIQVDEKTIGEP--GWLYGSFQ--GNFGWFPCNYVEK 838
Cdd:cd11791      2 LRVLYPYTPQEEDELELVPGDYIYVSPEELDSSsdGWVEGTSWltGCSGLLPENYTEK 59

First Src Homology 3 domain (SH3A) of Cbl-interacting protein of 85 kDa; CIN85, also called SH3 domain-containing kinase-binding protein 1 (SH3KBP1) or CD2-binding protein 3 (CD2BP3) or Ruk, is an adaptor protein that is involved in the downregulation of receptor tyrosine kinases by facilitating endocytosis through interaction with endophilin-associated ubiquitin ligase Cbl proteins. It is also important in many other cellular processes including vesicle-mediated transport, cytoskeletal remodelling, apoptosis, cell adhesion and migration, and viral infection, among others. CIN85 exists as multiple variants from alternative splicing; the main variant contains three SH3 domains, a proline-rich region, and a C-terminal coiled-coil domain. All of these domains enable CIN85 to bind various protein partners and assemble complexes that have been implicated in many different functions. This alignment model represents the first SH3 domain (SH3A) of CIN85; SH3A binds to internal proline-rich motifs within the proline-rich region. This intramolecular interaction serves as a regulatory mechanism to keep CIN85 in a closed conformation, preventing the recruitment of other proteins. SH3A has also been shown to bind ubiquitin and to an atypical PXXXPR motif at the C-terminus of Cbl and the cytoplasmic end of the cell adhesion protein CD2. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212985 [Multi-domain] Cd Length: 53 Bit Score: 42.19 E-value: 5.59e-05

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gi 1804876928 1079 AQVTSAYVASGSEQLSLAPGQLILILKKNSSGWWQGELQARgkkrqKGWFPASHVK 1134
Cdd:cd12052      2 AIVEFDYKAQHEDELTITVGDIITKIKKDDGGWWEGEIKGR-----RGLFPDNFVR 52

First Src Homology 3 domain (SH3A) of CD2-associated protein; CD2AP, also called CMS (Cas ligand with Multiple SH3 domains) or METS1 (Mesenchyme-to-Epithelium Transition protein with SH3 domains), is a cytosolic adaptor protein that plays a role in regulating the cytoskeleton. It is critical in cell-to-cell union necessary for kidney function. It also stabilizes the contact between a T cell and antigen-presenting cells. It is primarily expressed in podocytes at the cytoplasmic face of the slit diaphragm and serves as a linker anchoring podocin and nephrin to the actin cytoskeleton. CD2AP contains three SH3 domains, a proline-rich region, and a C-terminal coiled-coil domain. All of these domains enable CD2AP to bind various protein partners and assemble complexes that have been implicated in many different functions. This alignment model represents the first SH3 domain (SH3A) of CD2AP. SH3A binds to the PXXXPR motif present in c-Cbl and the cytoplasmic domain of cell adhesion protein CD2. Its interaction with CD2 anchors CD2 at sites of cell contact. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212986 Cd Length: 56 Bit Score: 42.52 E-value: 5.73e-05

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gi 1804876928  789 YRFEARSHDEMSFNSGDIIQvDEKTIGEPGWLYGSFQGNFGWFPCNYVEKM 839
Cdd:cd12053      6 YDYDAVHEDELTIRVGEIIR-NVKKLEEEGWLEGELNGRRGMFPDNFVKEI 55

Src homology 3 domain of Abl Interactor 2; Abi2 is highly expressed in the brain and eye. It regulates actin cytoskeletal reorganization at adherens junctions and dendritic spines, which is important in cell morphogenesis, migration, and cognitive function. Mice deficient with Abi2 show defects in orientation and migration of lens fibers, neuronal migration, dendritic spine morphology, as well as deficits in learning and memory. Abi proteins are adaptor proteins serving as binding partners and substrates of Abl tyrosine kinases. They are involved in regulating actin cytoskeletal reorganization and play important roles in membrane-ruffling, endocytosis, cell motility, and cell migration. Abi proteins contain a homeobox homology domain, a proline-rich region, and a SH3 domain. The SH3 domain of Abi binds to a PxxP motif in Abl. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212905 [Multi-domain] Cd Length: 61 Bit Score: 42.69 E-value: 5.75e-05

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gi 1804876928  787 ALYRFEARSHDEMSFNSGDIIQVDEKTigEPGWLYGSFQGNFGWFPCNYVEKM 839
Cdd:cd11972      7 AIYDYTKDKEDELSFQEGAIIYVIKKN--DDGWYEGVMNGVTGLFPGNYVESI 57

Arginine and glutamate-rich 1; ARGLU, arginine and glutamate-rich 1 protein family, is required for the oestrogen-dependent expression of ESR1 target genes. It functions in cooperation with MED1. The family of proteins is found in eukaryotes.

Pssm-ID: 405931 [Multi-domain] Cd Length: 151 Bit Score: 45.04 E-value: 5.92e-05

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gi 1804876928  698 EQLHKIKRDKLKEIERKRSEliQKKKLEDEAIRKAKQGKENLWRESLRKEEEEKQKRLQEEKTQEkvqEEERKVEEKQ 775
Cdd:pfam15346   26 EELEKRKDEIEAEVERRVEE--ARKIMEKQVLEELEREREAELEEERRKEEEERKKREELERILE---ENNRKIEEAQ 98

Third (or C-terminal) Src Homology 3 domain of Sorbin and SH3 domain containing (Sorbs) proteins and similar domains; This family, also called the vinexin family, is composed predominantly of adaptor proteins containing one sorbin homology (SoHo) and three SH3 domains. Members include the third SH3 domains of Sorbs1 (or ponsin), Sorbs2 (or ArgBP2), Vinexin (or Sorbs3), and similar domains. They are involved in the regulation of cytoskeletal organization, cell adhesion, and growth factor signaling. Members of this family bind multiple partners including signaling molecules like c-Abl, c-Arg, Sos, and c-Cbl, as well as cytoskeletal molecules such as vinculin and afadin. They may have overlapping functions. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212714 [Multi-domain] Cd Length: 55 Bit Score: 42.29 E-value: 5.95e-05

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gi 1804876928 1007 YIALYSYSSVEPGDLTFIEGEEILVTQK--DGeWWTGSIGdRT---GIFPSNYVKP 1057
Cdd:cd11780      2 YRALYSYTPQNEDELELREGDIVYVMEKcdDG-WFVGTSE-RTglfGTFPGNYVAR 55

Src homology 3 domain of Type I fungal Myosins; Type I myosins (myosin-I) are actin-dependent motors in endocytic actin structures and actin patches. They play roles in membrane traffic in endocytic and secretory pathways, cell motility, and mechanosensing. Saccharomyces cerevisiae has two myosins-I, Myo3 and Myo5, which are involved in endocytosis and the polarization of the actin cytoskeleton. Myosin-I contains an N-terminal actin-activated ATPase, a phospholipid-binding TH1 (tail homology 1) domain, and a C-terminal extension which includes an F-actin-binding TH2 domain, an SH3 domain, and an acidic peptide that participates in activating the Arp2/3complex. The SH3 domain of myosin-I is required for myosin-I-induced actin polymerization. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212792 [Multi-domain] Cd Length: 55 Bit Score: 42.37 E-value: 5.95e-05

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gi 1804876928 1155 AMYDYVANNEDELNFSKGQLINVLNKDDPDWWQGEINGVT--GLFPSNYVK 1203
Cdd:cd11858      4 ALYDFAGSVANELSLKKDDIVYIVQKEDNGWWLAKKLDESkeGWVPAAYLE 54

Src homology 3 domain of Lck Protein Tyrosine Kinase; Lck is a member of the Src subfamily of proteins, which are cytoplasmic (or non-receptor) PTKs. Lck is expressed in T-cells and natural killer cells. It plays a critical role in T-cell maturation, activation, and T-cell receptor (TCR) signaling. Lck phosphorylates ITAM (immunoreceptor tyr activation motif) sequences on several subunits of TCRs, leading to the activation of different second messenger cascades. Phosphorylated ITAMs serve as binding sites for other signaling factor such as Syk and ZAP-70, leading to their activation and propagation of downstream events. In addition, Lck regulates drug-induced apoptosis by interfering with the mitochondrial death pathway. The apototic role of Lck is independent of its primary function in T-cell signaling. Src kinases contain an N-terminal SH4 domain with a myristoylation site, followed by SH3 and SH2 domains, a tyr kinase domain, and a regulatory C-terminal region containing a conserved tyr. They are activated by autophosphorylation at the tyr kinase domain, but are negatively regulated by phosphorylation at the C-terminal tyr by Csk (C-terminal Src Kinase). The SH3 domain of Src kinases contributes to substrate recruitment by binding adaptor proteins/substrates, and regulation of kinase activity through an intramolecular interaction. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212938 [Multi-domain] Cd Length: 54 Bit Score: 42.12 E-value: 6.02e-05

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gi 1804876928 1008 IALYSYSSVEPGDLTFIEGEEILVTQKDGEWWTG---SIGDRtGIFPSNYV 1055
Cdd:cd12005      3 VALYSYEPSHDGDLGFEKGEKLRILEQSGEWWKAqslTTGQE-GFIPFNFV 52

Src Homology 3 domain of Sdc25/Cdc25 guanine nucleotide exchange factors; This subfamily is composed of the Saccharomyces cerevisiae guanine nucleotide exchange factors (GEFs) Sdc25 and Cdc25, and similar proteins. These GEFs regulate Ras by stimulating the GDP/GTP exchange on Ras. Cdc25 is involved in the Ras/PKA pathway that plays an important role in the regulation of metabolism, stress responses, and proliferation, depending on available nutrients and conditions. Proteins in this subfamily contain an N-terminal SH3 domain as well as REM (Ras exchanger motif) and RasGEF domains at the C-terminus. SH3 domains bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs; they play a role in the regulation of enzymes by intramolecular interactions, changing the subcellular localization of signal pathway components and mediate multiprotein complex assemblies.

Pssm-ID: 212816 Cd Length: 55 Bit Score: 42.27 E-value: 6.21e-05

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gi 1804876928 1008 IALYSYSSVEPGDLTFIEGEEILVTQKD--GeWWTGSIGDRTGI-----FPSNY 1054
Cdd:cd11883      3 VALYDFTPKSKNQLSFKAGDIIYVLNKDpsG-WWDGVIISSSGKvkrgwFPSNY 55

N-terminal Src homology 3 domain of Growth factor receptor-bound protein 2 (GRB2) and related proteins; This family includes the adaptor protein GRB2 and related proteins including Drosophila melanogaster Downstream of receptor kinase (DRK), Caenorhabditis elegans Sex muscle abnormal protein 5 (Sem-5), GRB2-related adaptor protein (GRAP), GRAP2, and similar proteins. Family members contain an N-terminal SH3 domain, a central SH2 domain, and a C-terminal SH3 domain. GRB2/Sem-5/DRK is a critical signaling molecule that regulates the Ras pathway by linking tyrosine kinases to the Ras guanine nucleotide releasing protein Sos (son of sevenless), which converts Ras to the active GTP-bound state. GRAP2 plays an important role in T cell receptor (TCR) signaling by promoting the formation of the SLP-76:LAT complex, which couples the TCR to the Ras pathway. GRAP acts as a negative regulator of T cell receptor (TCR)-induced lymphocyte proliferation by downregulating the signaling to the Ras/ERK pathway. The N-terminal SH3 domain of GRB2 binds to Sos and Sos-derived proline-rich peptides. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212738 [Multi-domain] Cd Length: 52 Bit Score: 41.96 E-value: 6.33e-05

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gi 1804876928  924 AQALCSWTAKKDNHLNFSKHDIITVL--EQQENWWFGEVHGGRGWFPKSYV 972
Cdd:cd11804      2 AVAKHDFKATAEDELSFKKGSILKVLnmEDDPNWYKAELDGKEGLIPKNYI 52

Src homology 3 domain of the Rho guanine nucleotide exchange factors ARHGEF16 and ARHGEF26; ARHGEF16, also called ephexin-4, acts as a GEF for RhoG, activating it by exchanging bound GDP for free GTP. RhoG is a small GTPase that is a crucial regulator of Rac in migrating cells. ARHGEF16 interacts directly with the ephrin receptor EphA2 and mediates cell migration and invasion in breast cancer cells by activating RhoG. ARHGEF26, also called SGEF (SH3 domain-containing guanine exchange factor), also activates RhoG. It is highly expressed in liver and may play a role in regulating membrane dynamics. ARHGEF16 and ARHGEF26 contain RhoGEF (also called Dbl-homologous or DH), Pleckstrin Homology (PH), and SH3 domains. The SH3 domains of ARHGEFs play an autoinhibitory role through intramolecular interactions with a proline-rich region N-terminal to the DH domain. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212871 Cd Length: 55 Bit Score: 42.14 E-value: 6.34e-05

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gi 1804876928 1080 QVTSAYVASGSEQLSLAPGQLILILKKNSSGWWQGElqaRGKKRQKGWFPASHVK 1134
Cdd:cd11938      3 EIIKAYTAKQPDELSLQQADVVLVLQTESDGWYYGE---RLRDGERGWFPSSCAK 54

Pleckstrin homology domain-containing family G member 5 and 6 pleckstrin homology (PH) domain; PLEKHG5 has a RhoGEF DH/double-homology domain in tandem with a PH domain which is involved in phospholipid binding. PLEKHG5 activates the nuclear factor kappa B (NFKB1) signaling pathway. Mutations in PLEKHG5 are associated with autosomal recessive distal spinal muscular atrophy. PLEKHG6 (also called MyoGEF) has no known function to date. PH domains have diverse functions, but in general are involved in targeting proteins to the appropriate cellular location or in the interaction with a binding partner. They share little sequence conservation, but all have a common fold, which is electrostatically polarized. Less than 10% of PH domains bind phosphoinositide phosphates (PIPs) with high affinity and specificity. PH domains are distinguished from other PIP-binding domains by their specific high-affinity binding to PIPs with two vicinal phosphate groups: PtdIns(3,4)P2, PtdIns(4,5)P2 or PtdIns(3,4,5)P3 which results in targeting some PH domain proteins to the plasma membrane. A few display strong specificity in lipid binding. Any specificity is usually determined by loop regions or insertions in the N-terminus of the domain, which are not conserved across all PH domains. PH domains are found in cellular signaling proteins such as serine/threonine kinase, tyrosine kinases, regulators of G-proteins, endocytotic GTPases, adaptors, as well as cytoskeletal associated molecules and in lipid associated enzymes.

Pssm-ID: 270064 Cd Length: 100 Bit Score: 43.75 E-value: 6.35e-05

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1804876928 1454 RKLLHSG--KLYKTKSNK-ELHGFLFNDFLLLTymvKQfaVSSGSEKLfssksnaqfKMYKTPIFLNEVLVKLPTDPSSd 1530
Cdd:cd13244      1 RRLLLEGdlRLKEGKGSKvDVHCFLFTDMLLIC---KP--VKRKKDRL---------KVIRPPYLVDKLVVQELKDPGG- 65

                           90       100       110
                   ....*....|....*....|....*....|....*..
gi 1804876928 1531 epvFHISHIDR------VYTLRTDNINERTAWVQKIK 1561
Cdd:cd13244     66 ---FLLVYLNEfhtavaAYTFQTSSQEDTRRWLDAIR 99

Third Src homology 3 domain (or SH3C) of Intersectin-1; Intersectin-1 (ITSN1) is an adaptor protein that functions in exo- and endocytosis, actin cytoskeletal reorganization, and signal transduction. It plays a role in clathrin-coated pit (CCP) formation. It binds to many proteins through its multidomain structure and facilitate the assembly of multimeric complexes. ITSN1 localizes in membranous organelles, CCPs, the Golgi complex, and may be involved in the cell membrane trafficking system. It exists in alternatively spliced short and long isoforms. The short isoform contains two Eps15 homology domains (EH1 and EH2), a coiled-coil region and five SH3 domains (SH3A-E), while the long isoform, in addition, contains RhoGEF (also called Dbl-homologous or DH), Pleckstrin homology (PH) and C2 domains. The third SH3 domain (or SH3C) of ITSN1 has been shown to bind many proteins including dynamin1/2, CIN85, c-Cbl, SHIP2, Reps1, synaptojanin-1, and WNK, among others. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212924 Cd Length: 52 Bit Score: 42.28 E-value: 6.42e-05

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|..
gi 1804876928  785 YKALYRFEARSHDEMSFNSGDIIQVDEKtigEPGWLYGSFQGNFGWFPCNYV 836
Cdd:cd11991      2 YVAMYTYESNEQGDLTFQQGDVILVTKK---DGDWWTGTVGDKTGVFPSNYV 50

Src homology 3 domain of Lyn Protein Tyrosine Kinase; Lyn is a member of the Src subfamily of proteins, which are cytoplasmic (or non-receptor) PTKs. Lyn is expressed in B lymphocytes and myeloid cells. It exhibits both positive and negative regulatory roles in B cell receptor (BCR) signaling. Lyn, as well as Fyn and Blk, promotes B cell activation by phosphorylating ITAMs (immunoreceptor tyr activation motifs) in CD19 and in Ig components of BCR. It negatively regulates signaling by its unique ability to phosphorylate ITIMs (immunoreceptor tyr inhibition motifs) in cell surface receptors like CD22 and CD5. Lyn also plays an important role in G-CSF receptor signaling by phosphorylating a variety of adaptor molecules. Src kinases contain an N-terminal SH4 domain with a myristoylation site, followed by SH3 and SH2 domains, a tyr kinase domain, and a regulatory C-terminal region containing a conserved tyr. They are activated by autophosphorylation at the tyr kinase domain, but are negatively regulated by phosphorylation at the C-terminal tyr by Csk (C-terminal Src Kinase). The SH3 domain of Src kinases contributes to substrate recruitment by binding adaptor proteins/substrates, and regulation of kinase activity through an intramolecular interaction. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212937 [Multi-domain] Cd Length: 56 Bit Score: 42.29 E-value: 6.53e-05

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|..
gi 1804876928 1153 VIAMYDYVANNEDELNFSKGQLINVLnKDDPDWWQGE--INGVTGLFPSNYV 1202
Cdd:cd12004      2 VVALYPYDGIHEDDLSFKKGEKLKVI-EEHGEWWKARslTTKKEGFIPSNYV 52

Src Homology 3 domain of Interleukin-2-inducible T-cell Kinase; ITK (also known as Tsk or Emt) is a cytoplasmic (or nonreceptor) tyr kinase containing Src homology protein interaction domains (SH3, SH2) N-terminal to the catalytic tyr kinase domain. It also contains an N-terminal pleckstrin homology (PH) domain, which binds the products of PI3K and allows membrane recruitment and activation, and the Tec homology (TH) domain, which contains proline-rich and zinc-binding regions. ITK is expressed in T-cells and mast cells, and is important in their development and differentiation. Of the three Tec kinases expressed in T-cells, ITK plays the predominant role in T-cell receptor (TCR) signaling. It is activated by phosphorylation upon TCR crosslinking and is involved in the pathway resulting in phospholipase C-gamma1 activation and actin polymerization. It also plays a role in the downstream signaling of the T-cell costimulatory receptor CD28, the T-cell surface receptor CD2, and the chemokine receptor CXCR4. In addition, ITK is crucial for the development of T-helper(Th)2 effector responses. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212841 [Multi-domain] Cd Length: 56 Bit Score: 42.31 E-value: 6.69e-05

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|.
gi 1804876928 1153 VIAMYDYVANNEDELNFSKGQLINVLNKDDPDWWQ-GEINGVTGLFPSNYV 1202
Cdd:cd11908      3 VIALYDYQTNDPQELALRYNEEYHLLDSSEIHWWRvQDKNGHEGYVPSSYL 53

Second Src Homology 3 domain of Nck2 adaptor protein; Nck2 (also called Nckbeta or Growth factor receptor-bound protein 4, Grb4) plays a crucial role in connecting signaling pathways of tyrosine kinase receptors and important effectors in actin dynamics and cytoskeletal remodeling. It binds neuronal signaling proteins such as ephrinB and Disabled-1 (Dab-1) exclusively. Nck adaptor proteins regulate actin cytoskeleton dynamics by linking proline-rich effector molecules to protein tyrosine kinases and phosphorylated signaling intermediates. They contain three SH3 domains and a C-terminal SH2 domain. They function downstream of the PDGFbeta receptor and are involved in Rho GTPase signaling and actin dynamics. Vertebrates contain two Nck adaptor proteins: Nck1 (also called Nckalpha) and Nck2, which show partly overlapping functions but also bind distinct targets. The second SH3 domain of Nck appears to prefer ligands containing the APxxPxR motif. SH3 domains are protein interaction domains that usually bind to proline-rich ligands with moderate affinity and selectivity, preferentially a PxxP motif. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212835 [Multi-domain] Cd Length: 55 Bit Score: 42.30 E-value: 7.04e-05

                           10        20        30        40
                   ....*....|....*....|....*....|....*....|....*
gi 1804876928  929 SWTAKKDNHLNFSKHDIITVLEQ-QENWWFGEVHGGRGWFPKSYV 972
Cdd:cd11902      8 AYVAEREDELSLVKGSRVTVMEKcSDGWWRGSYNGQIGWFPSNYV 52

Third Src homology 3 domain of Tyrosine kinase substrate (Tks) proteins; Tks proteins are Src substrates and scaffolding proteins that play important roles in the formation of podosomes and invadopodia, the dynamic actin-rich structures that are related to cell migration and cancer cell invasion. Vertebrates contain two Tks proteins, Tks4 (Tyr kinase substrate with four SH3 domains) and Tks5 (Tyr kinase substrate with five SH3 domains), which display partially overlapping but non-redundant functions. Both associate with the ADAMs family of transmembrane metalloproteases, which function as sheddases and mediators of cell and matrix interactions. Tks5 interacts with N-WASP and Nck, while Tks4 is essential for the localization of MT1-MMP (membrane-type 1 matrix metalloproteinase) to invadopodia. Tks proteins contain an N-terminal Phox homology (PX) domain and four or five SH3 domains. This model characterizes the third SH3 domain of Tks proteins. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212950 Cd Length: 53 Bit Score: 42.05 E-value: 7.10e-05

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....
gi 1804876928  785 YKALYRFEARSHDEMSFNSGDIIQVDEKTIGepGWLYGSFQGNFGWFPCNYVEK 838
Cdd:cd12017      2 YFTIGEFQATIQDGISFQKGQKVEVIDKNPS--GWWYVKIDGKEGWAPSSYIEK 53

Src homology 3 domain of an unknown subfamily of proteins with similarity to Protein kinase C and Casein kinase Substrate in Neurons (PACSIN) proteins; PACSINs, also called Synaptic dynamin-associated proteins (Syndapins), act as regulators of cytoskeletal and membrane dynamics. They bind both dynamin and Wiskott-Aldrich syndrome protein (WASP), and may provide direct links between the actin cytoskeletal machinery through WASP and dynamin-dependent endocytosis. Vetebrates harbor three isoforms with distinct expression patterns and specific functions. PACSINs contain an N-terminal F-BAR domain and a C-terminal SH3 domain. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212932 [Multi-domain] Cd Length: 56 Bit Score: 42.23 E-value: 7.19e-05

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|
gi 1804876928 1009 ALYSYSSVEPGDLTFIEGEEIL-VTQKDGEWWTGSIGD--RTGIFPSNYV 1055
Cdd:cd11999      6 AVYDYTGQEPDELSFKAGEELLkVEDEDEQGWCKGVTDggAVGLYPANYV 55

C-terminal (or second) Src homology 3 domain of VAV proteins; VAV proteins function both as cytoplasmic guanine nucleotide exchange factors (GEFs) for Rho GTPases and scaffold proteins and they play important roles in cell signaling by coupling cell surface receptors to various effector functions. They play key roles in processes that require cytoskeletal reorganization including immune synapse formation, phagocytosis, cell spreading, and platelet aggregation, among others. Vertebrates have three VAV proteins (VAV1, VAV2, and VAV3). VAV proteins contain several domains that enable their function: N-terminal calponin homology (CH), acidic, RhoGEF (also called Dbl-homologous or DH), Pleckstrin Homology (PH), C1 (zinc finger), SH2, and two SH3 domains. The SH3 domain of VAV is involved in the localization of proteins to specific sites within the cell, by interacting with proline-rich sequences within target proteins. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212764 [Multi-domain] Cd Length: 54 Bit Score: 41.85 E-value: 7.33e-05

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|.
gi 1804876928 1008 IALYSYSSVEPGDLTFIEGEEILVTQKDGE--WWTGSIGDRTGIFPSNYVK 1056
Cdd:cd11830      3 KARYDFCARDMRELSLKEGDVVKIYNKKGQqgWWRGEINGRIGWFPSTYVE 53

Src Homology 3 domain of GTPase Regulator Associated with Focal adhesion kinase; GRAF, also called Rho GTPase activating protein 26 (ARHGAP26), Oligophrenin-1-like (OPHN1L) or GRAF1, is a GAP with activity towards RhoA and Cdc42 and is only weakly active towards Rac1. It influences Rho-mediated cytoskeletal rearrangements and binds focal adhesion kinase (FAK), which is a critical component of integrin signaling. It is essential for the major clathrin-independent endocytic pathway mediated by pleiomorphic membranes. GRAF contains an N-terminal BAR domain, followed by a Pleckstrin homology (PH) domain, a Rho GAP domain, and a C-terminal SH3 domain. The SH3 domain of GRAF binds PKNbeta, a target of the small GTPase Rho. SH3 domains bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs; they play a role in the regulation of enzymes by intramolecular interactions, changing the subcellular localization of signal pathway components and mediate multiprotein complex assemblies.

Pssm-ID: 212997 Cd Length: 56 Bit Score: 42.02 E-value: 7.46e-05

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|..
gi 1804876928  786 KALYRFEARSHDEMSFNSGDIIQvDEKTIGEPGWLYGSFQGNFGWFPCNYVE 837
Cdd:cd12064      4 KALYACKAEHDSELSFTAGTVFD-NVHPSQEPGWLEGTLNGKTGLIPENYVE 54

Second Src Homology 3 domain of FCH and double SH3 domains protein 2; FCHSD2 has a domain structure consisting of an N-terminal F-BAR (FES-CIP4 Homology and Bin/Amphiphysin/Rvs), two SH3, and C-terminal proline-rich domains. It has only been characterized in silico and its function is unknown. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212827 Cd Length: 56 Bit Score: 42.23 E-value: 7.48e-05

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|...
gi 1804876928  786 KALYRFEARSHDEMSFNSGDIIQV-DEKTIGEPGWLYGSFQGNFGWFPCNYVE 837
Cdd:cd11894      3 KALYDYEGQTDDELSFPEGAIIRIlNKENQDDDGFWEGEFNGRIGVFPSVLVE 55

First C-terminal Src homology 3 domain of Fungal Actin-binding protein 1; Abp1 is an adaptor protein that functions in receptor-mediated endocytosis and vesicle trafficking. It contains an N-terminal actin-binding module, the actin-depolymerizing factor (ADF) homology domain, a central proline-rich region, and a C-terminal SH3 domain (many yeast Abp1 proteins contain two C-terminal SH3 domains). Yeast Abp1 also contains two acidic domains that bind directly to the Arp2/3 complex, which is required to initiate actin polymerization. The SH3 domain of yeast Abp1 binds and localizes the kinases, Ark1p and Prk1p, which facilitate actin patch disassembly following vesicle internalization. It also mediates the localization to the actin patch of the synaptojanin-like protein, Sjl2p, which plays a key role in endocytosis. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212895 [Multi-domain] Cd Length: 54 Bit Score: 42.09 E-value: 7.93e-05

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|..
gi 1804876928 1008 IALYSYSSVEPGDLTFIEGEEIL-VTQKDGEWWTG--SIGDRtGIFPSNYVK 1056
Cdd:cd11962      3 VVLYDYEKDEDNEIELVEGEIVTnIEMVDEDWWMGtnSKGES-GLFPSNYVE 53

Trichohyalin-plectin-homology domain; This family is a mixtrue of two different families of eukaryotic proteins. Trichoplein or mitostatin, was first defined as a meiosis-specific nuclear structural protein. It has since been linked with mitochondrial movement. It is associated with the mitochondrial outer membrane, and over-expression leads to reduction in mitochondrial motility whereas lack of it enhances mitochondrial movement. The activity appears to be mediated through binding the mitochondria to the actin intermediate filaments (IFs). The family is in the trichohyalin-plectin-homology domain.

Pssm-ID: 464007 [Multi-domain] Cd Length: 341 Bit Score: 46.84 E-value: 8.25e-05

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1804876928  384 QKIQEEEPQKKLPVtfEDKRKANYE---RGNVELEKRRQaLMEQQQREAERKA---QKEKEEWERK-QRELQEQEWKKQL 456
Cdd:pfam13868  108 ERIQEEDQAEAEEK--LEKQRQLREeidEFNEEQAEWKE-LEKEEEREEDERIleyLKEKAEREEErEAEREEIEEEKER 184

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1804876928  457 ELEKRLEKQRELERQREEERRKEIERREAAKQELERQRRLEWE--RIRRQELLNQRNREQEEIvrlnskkKSLHLELEAl 534
Cdd:pfam13868  185 EIARLRAQQEKAQDEKAERDELRAKLYQEEQERKERQKEREEAekKARQRQELQQAREEQIEL-------KERRLAEEA- 256

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1804876928  535 nGKHQQISGRLqdvrLRKQTQKTEIEVLDKQcdleimEIKQLQQELQDYQNKLIYLVpEKQLLNERIKNMQlgntpdlgi 614
Cdd:pfam13868  257 -EREEEEFERM----LRKQAEDEEIEQEEAE------KRRMKRLEHRRELEKQIEER-EEQRAAEREEELE--------- 315

                          250       260       270
                   ....*....|....*....|....*....|....
gi 1804876928  615 dllhkkslEKEELCQRLKEQLDALEKETASKLSE 648
Cdd:pfam13868  316 --------EGERLREEEAERRERIEEERQKKLKE 341

Src homology 3 domain of Phospholipase C (PLC) gamma 2; PLCgamma2 is primarily expressed in haematopoietic cells, specifically in B cells. It is activated by tyrosine phosphorylation by B cell receptor (BCR) kinases and is recruited to the plasma membrane where its substrate is located. It is required in pre-BCR signaling and in the maturation of B cells. PLCs catalyze the hydrolysis of phosphatidylinositol (4,5)-bisphosphate [PtdIns(4,5)P2] to produce Ins(1,4,5)P3 and diacylglycerol (DAG). Ins(1,4,5)P3 initiates the calcium signaling cascade while DAG functions as an activator of PKC. PLCgamma contains a Pleckstrin homology (PH) domain followed by an elongation factor (EF) domain, two catalytic regions of PLC domains that flank two tandem SH2 domains, followed by a SH3 domain and C2 domain. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212902 Cd Length: 55 Bit Score: 41.75 E-value: 8.71e-05

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....*
gi 1804876928  786 KALYRFEARSHDEMSFNSGDIIQVDEKTIGepGWLYGSFQGNFG-WFPCNYVEKM 839
Cdd:cd11969      3 KALYDYRAKRSDELSFCKGALIHNVSKETG--GWWKGDYGGKVQhYFPSNYVEDV 55

Third Src homology 3 domain (or SH3C) of Intersectin-1; Intersectin-1 (ITSN1) is an adaptor protein that functions in exo- and endocytosis, actin cytoskeletal reorganization, and signal transduction. It plays a role in clathrin-coated pit (CCP) formation. It binds to many proteins through its multidomain structure and facilitate the assembly of multimeric complexes. ITSN1 localizes in membranous organelles, CCPs, the Golgi complex, and may be involved in the cell membrane trafficking system. It exists in alternatively spliced short and long isoforms. The short isoform contains two Eps15 homology domains (EH1 and EH2), a coiled-coil region and five SH3 domains (SH3A-E), while the long isoform, in addition, contains RhoGEF (also called Dbl-homologous or DH), Pleckstrin homology (PH) and C2 domains. The third SH3 domain (or SH3C) of ITSN1 has been shown to bind many proteins including dynamin1/2, CIN85, c-Cbl, SHIP2, Reps1, synaptojanin-1, and WNK, among others. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212924 Cd Length: 52 Bit Score: 41.89 E-value: 8.71e-05

                           10        20        30        40
                   ....*....|....*....|....*....|....*....|....*...
gi 1804876928  926 ALCSWTAKKDNHLNFSKHDIITVLEQQENWWFGEVHGGRGWFPKSYVK 973
Cdd:cd11991      4 AMYTYESNEQGDLTFQQGDVILVTKKDGDWWTGTVGDKTGVFPSNYVR 51

chromosome segregation protein SMC, common bacterial type; SMC (structural maintenance of chromosomes) proteins bind DNA and act in organizing and segregating chromosomes for partition. SMC proteins are found in bacteria, archaea, and eukaryotes. This family represents the SMC protein of most bacteria. The smc gene is often associated with scpB (TIGR00281) and scpA genes, where scp stands for segregation and condensation protein. SMC was shown (in Caulobacter crescentus) to be induced early in S phase but present and bound to DNA throughout the cell cycle. [Cellular processes, Cell division, DNA metabolism, Chromosome-associated proteins]

Pssm-ID: 274008 [Multi-domain] Cd Length: 1179 Bit Score: 47.74 E-value: 8.91e-05

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1804876928  401 DKRKANYERGNVELEKRRQALMEQQQREAERKAQKEKEEWE-RKQRELQEQEWKKQLELEKRLEKQRELERQREEERRKE 479
Cdd:TIGR02168  718 RKELEELSRQISALRKDLARLEAEVEQLEERIAQLSKELTElEAEIEELEERLEEAEEELAEAEAEIEELEAQIEQLKEE 797

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1804876928  480 IERREAAKQELERQRRLEWERI-----RRQELLNQRNREQEEIVRLNSKKKSLHLELEALNGKHQQ-------ISGRLQD 547
Cdd:TIGR02168  798 LKALREALDELRAELTLLNEEAanlreRLESLERRIAATERRLEDLEEQIEELSEDIESLAAEIEEleelieeLESELEA 877

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1804876928  548 VRLRKQTQKTEIEVLDKQCDLEIMEIKQLQQELQDYQNKLiylvpekQLLNERIKNMQlgntpdlgidllhkksLEKEEL 627
Cdd:TIGR02168  878 LLNERASLEEALALLRSELEELSEELRELESKRSELRREL-------EELREKLAQLE----------------LRLEGL 934

                          250
                   ....*....|.
gi 1804876928  628 CQRLKEQLDAL 638
Cdd:TIGR02168  935 EVRIDNLQERL 945

Src Homology 3 domain of fungal peroxisomal membrane protein Pex13p; Pex13p, located in the peroxisomal membrane, contains two transmembrane regions and a C-terminal SH3 domain. It binds to the peroxisomal targeting type I (PTS1) receptor Pex5p and the docking factor Pex14p through its SH3 domain. It is essential for both PTS1 and PTS2 protein import pathways into the peroxisomal matrix. Pex13p binds Pex14p, which contains a PxxP motif, in a classical fashion to the proline-rich ligand binding site of its SH3 domain. It binds the WxxxF/Y motif of Pex5p in a novel site that does not compete with Pex14p binding. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212705 [Multi-domain] Cd Length: 60 Bit Score: 41.88 E-value: 8.99e-05

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....*
gi 1804876928 1009 ALYSYSSVEPG-DLTFIEGEEILVTQK------DGEWWTGSIGD-RTGIFPSNYV 1055
Cdd:cd11771      4 ALYDFTPENPEmELSLKKGDIVAVLSKtdplgrDSEWWKGRTRDgRIGWFPSNYV 58

First or N-terminal Src homology 3 domain of the p47phox subunit of NADPH oxidase, also called Neutrophil Cytosolic Factor 1; p47phox, or NCF1, is a cytosolic subunit of the phagocytic NADPH oxidase complex (also called Nox2 or gp91phox), which plays a key role in the ability of phagocytes to defend against bacterial infections. NADPH oxidase catalyzes the transfer of electrons from NADPH to oxygen during phagocytosis forming superoxide and reactive oxygen species. p47phox is required for activation of NADH oxidase and plays a role in translocation. It contains an N-terminal Phox homology (PX) domain, tandem SH3 domains (N-SH3 and C-SH3), a polybasic/autoinhibitory region, and a C-terminal proline-rich region (PRR). This model characterizes the first SH3 domain (or N-SH3) of p47phox. In its inactive state, the tandem SH3 domains interact intramolecularly with the autoinhibitory region; upon activation, the tandem SH3 domains are exposed through a conformational change, resulting in their binding to the PRR of p22phox and the activation of NADPH oxidase. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212954 [Multi-domain] Cd Length: 53 Bit Score: 41.87 E-value: 9.28e-05

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|...
gi 1804876928  785 YKALYRFEARSHDEMSFNSGDIIQVDEKTigEPGWLYGSFQGNFGWFPCNYVE 837
Cdd:cd12021      2 YRAIADYEKSSKSEMALKTGDVVEVVEKS--ENGWWFCQLKAKRGWVPASYLE 52

Src Homology 3 domain of GTPase Regulator Associated with Focal adhesion kinase 2; GRAF2, also called Rho GTPase activating protein 10 (ARHGAP10) or PS-GAP, is a GAP with activity towards Cdc42 and RhoA. It regulates caspase-activated p21-activated protein kinase-2 (PAK-2p34). GRAF2 interacts with PAK-2p34, leading to its stabilization and decrease of cell death. It is highly expressed in skeletal muscle, and is involved in alpha-catenin recruitment at cell-cell junctions. GRAF2 contains an N-terminal BAR domain, followed by a Pleckstrin homology (PH) domain, a Rho GAP domain, and a C-terminal SH3 domain. The SH3 domain of GRAF binds PKNbeta, a target of the small GTPase Rho. SH3 domains bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs; they play a role in the regulation of enzymes by intramolecular interactions, changing the subcellular localization of signal pathway components and mediate multiprotein complex assemblies.

Pssm-ID: 212998 [Multi-domain] Cd Length: 54 Bit Score: 41.90 E-value: 9.42e-05

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|.
gi 1804876928 1155 AMYDYVANNEDELNFSKGQLI-NVLNKDDPDWWQGEINGVTGLFPSNYVKM 1204
Cdd:cd12065      4 AVYPCEAEHSSELSFEVGAIFeDVTLSREPGWLEGTLNGKRGLIPENYVEI 54

Src homology 3 domain of Growth Arrest Specific protein 7; GAS7 is mainly expressed in the brain and is required for neurite outgrowth. It may also play a role in the protection and migration of embryonic stem cells. Treatment-related acute myeloid leukemia (AML) has been reported resulting from mixed-lineage leukemia (MLL)-GAS7 translocations as a complication of primary cancer treatment. GAS7 contains an N-terminal SH3 domain, followed by a WW domain, and a central F-BAR domain. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212763 [Multi-domain] Cd Length: 52 Bit Score: 41.73 E-value: 9.46e-05

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|..
gi 1804876928  786 KALYRFEARSHDE-MSFNSGDIIQVDEktIGEPGWLYGSFQGNFGWFPCNYV 836
Cdd:cd11829      3 RTLYAFTGEQHQQgLSFEAGELIRVLQ--APDGGWWEGEKDGLRGWFPASYV 52

Src Homology 3 domain of Sdc25/Cdc25 guanine nucleotide exchange factors; This subfamily is composed of the Saccharomyces cerevisiae guanine nucleotide exchange factors (GEFs) Sdc25 and Cdc25, and similar proteins. These GEFs regulate Ras by stimulating the GDP/GTP exchange on Ras. Cdc25 is involved in the Ras/PKA pathway that plays an important role in the regulation of metabolism, stress responses, and proliferation, depending on available nutrients and conditions. Proteins in this subfamily contain an N-terminal SH3 domain as well as REM (Ras exchanger motif) and RasGEF domains at the C-terminus. SH3 domains bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs; they play a role in the regulation of enzymes by intramolecular interactions, changing the subcellular localization of signal pathway components and mediate multiprotein complex assemblies.

Pssm-ID: 212816 Cd Length: 55 Bit Score: 41.50 E-value: 9.57e-05

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....
gi 1804876928  787 ALYRFEARSHDEMSFNSGDIIQVDEKtiGEPGW-----LYGSFQGNFGWFPCNY 835
Cdd:cd11883      4 ALYDFTPKSKNQLSFKAGDIIYVLNK--DPSGWwdgviISSSGKVKRGWFPSNY 55

Second C-terminal Src homology 3 domain of Dynamin Binding Protein, also called Tuba, and similar domains; DNMBP or Tuba is a cdc42-specific guanine nucleotide exchange factor (GEF) that contains four N-terminal SH3 domains, a central RhoGEF [or Dbl homology (DH)] domain followed by a Bin/Amphiphysin/Rvs (BAR) domain, and two C-terminal SH3 domains. It provides a functional link between dynamin, Rho GTPase signaling, and actin dynamics. It plays an important role in regulating cell junction configuration. The C-terminal SH3 domains of DNMBP bind to N-WASP and Ena/VASP proteins, which are key regulatory proteins of the actin cytoskeleton. Also included in this subfamily is the second C-terminal SH3 domain of Rho guanine nucleotide exchange factor 37 (ARHGEF37), whose function is still unknown. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212734 [Multi-domain] Cd Length: 57 Bit Score: 41.59 E-value: 9.66e-05

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....*.
gi 1804876928  785 YKALYRFEARSHDEMSFNSGDIIQVDEK--TIGEPGWLYGSFQGNFGWFPCNYVEK 838
Cdd:cd11800      2 YYALYTFEARSPGELSVTEGQVVTVLEKhdLKGNPEWWLVEDRGKQGYVPSNYLAK 57

Uncharacterized conserved protein, contains a C-terminal ATPase domain [Function unknown];

Pssm-ID: 443941 [Multi-domain] Cd Length: 1089 Bit Score: 47.60 E-value: 9.67e-05

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1804876928  429 AERKAQKEKEEwERKQRELQE-QEWKKQLELE-KRLEKQrelerqreeerrkeierreaaKQELERQRRLEWERIRRQEL 506
Cdd:COG4913    609 RAKLAALEAEL-AELEEELAEaEERLEALEAElDALQER---------------------REALQRLAEYSWDEIDVASA 666

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1804876928  507 lnqrnreQEEIVRLNSKKKslhlELEALNGKHQQISGRLQDVRLRKQTQKTEIEVLDKQCDLEIMEIKQLQQELQDYQNK 586
Cdd:COG4913    667 -------EREIAELEAELE----RLDASSDDLAALEEQLEELEAELEELEEELDELKGEIGRLEKELEQAEEELDELQDR 735

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1804876928  587 L-----IYLVPEKQLLNERIKNmqlgntpdLGIDLLHKkslekeELCQRLKEQLDALEKETASKLSE----MDSFNNQLK 657
Cdd:COG4913    736 LeaaedLARLELRALLEERFAA--------ALGDAVER------ELRENLEERIDALRARLNRAEEEleraMRAFNREWP 801

                          250       260       270       280       290       300       310       320
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1804876928  658 C--GNMDDSVlqcllsllsclnnlflllkELRESYntqqlaLEQLHKIKRDKLKEIERKRSELIQkkkledeaiRKAKQG 735
Cdd:COG4913    802 AetADLDADL-------------------ESLPEY------LALLDRLEEDGLPEYEERFKELLN---------ENSIEF 847

                          330       340
                   ....*....|....*....|..
gi 1804876928  736 KENLwRESLRKEEEEKQKRLQE 757
Cdd:COG4913    848 VADL-LSKLRRAIREIKERIDP 868

EF-hand domain pair;

Pssm-ID: 463900 [Multi-domain] Cd Length: 67 Bit Score: 41.86 E-value: 9.74e-05

                           10        20        30        40        50        60
                   ....*....|....*....|....*....|....*....|....*....|....*....|....
gi 1804876928  283 KYRQKFNSLDKSMSGYLSG--FQA--RNALLQSNLSQTQLATIWTLADIDGDGQLRAEEFILAM 342
Cdd:pfam13499    3 KLKEAFKLLDSDGDGYLDVeeLKKllRKLEEGEPLSDEEVEELFKEFDLDKDGRISFEEFLELY 66

Src homology 3 domain of the Rho guanine nucleotide exchange factors ARHGEF5 and ARHGEF19; ARHGEF5, also called ephexin-3 or TIM (Transforming immortalized mammary oncogene), is a potent activator of RhoA and it plays roles in regulating cell shape, adhesion, and migration. It binds to the SH3 domain of Src and is involved in regulating Src-induced podosome formation. ARHGEF19, also called ephexin-2 or WGEF (weak-similarity GEF), is highly expressed in the intestine, liver, heart and kidney. It activates RhoA, Cdc42, and Rac 1, and has been shown to activate RhoA in the Wnt-PCP (planar cell polarity) pathway. It is involved in the regulation of cell polarity and cytoskeletal reorganization. ARHGEF5 and ARHGEF19 contain RhoGEF (also called Dbl-homologous or DH), Pleckstrin Homology (PH), and SH3 domains. The SH3 domains of ARHGEFs play an autoinhibitory role through intramolecular interactions with a proline-rich region N-terminal to the DH domain. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212873 Cd Length: 55 Bit Score: 41.70 E-value: 1.01e-04

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....*.
gi 1804876928 1080 QVTSAYVASGSEQLSLAPGQLILILKKNSSGWWQGelqARGKKRQKGWFPASHVKL 1135
Cdd:cd11940      3 QCIRSYKAQENDELTLEKADIIMVRQQSSDGWLEG---VRLSDGERGWFPQSHVEE 55

Septal ring factor EnvC, activator of murein hydrolases AmiA and AmiB [Cell cycle control, cell division, chromosome partitioning];

Pssm-ID: 443969 [Multi-domain] Cd Length: 377 Bit Score: 46.68 E-value: 1.02e-04

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1804876928  413 ELEKRRQALmEQQQREAERKAQKEKEEWERKQRELQEQEWK--------KQLELE--------KRLEKQRELERQREEER 476
Cdd:COG4942     24 EAEAELEQL-QQEIAELEKELAALKKEEKALLKQLAALERRiaalarriRALEQElaaleaelAELEKEIAELRAELEAQ 102

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1804876928  477 RKEIERREAAKQELERQRRLEW--------ERIRRQELLNQRNREQEEIVRlnskkkSLHLELEALNGKHQQISGRLQDV 548
Cdd:COG4942    103 KEELAELLRALYRLGRQPPLALllspedflDAVRRLQYLKYLAPARREQAE------ELRADLAELAALRAELEAERAEL 176

                          170       180       190       200       210
                   ....*....|....*....|....*....|....*....|....*....|....*..
gi 1804876928  549 RLRKQTQKTEIEVLDKQCDLEIMEIKQLQQELQDYQNKLIYLVPEKQLLNERIKNMQ 605
Cdd:COG4942    177 EALLAELEEERAALEALKAERQKLLARLEKELAELAAELAELQQEAEELEALIARLE 233

Src homology 3 domain of Src-Like Adaptor Protein 2; SLAP2 plays a role in c-Cbl-dependent regulation of CSF1R, a tyrosine kinase important for myeloid cell growth and differentiation. It has been shown to interact with CSF1R, c-Cbl, LAT, CD247, and Zap70. SLAPs are adaptor proteins with limited similarity to Src family tyrosine kinases. They contain an N-terminal SH3 domain followed by an SH2 domain, and a unique C-terminal sequence. They function in regulating the signaling, ubiquitination, and trafficking of T-cell receptor (TCR) and B-cell receptor (BCR) components. The SH3 domain of SLAP forms a complex with v-Abl. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212944 Cd Length: 55 Bit Score: 41.65 E-value: 1.05e-04

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|
gi 1804876928 1008 IALYSYSSVEPGDLTFIEGEEILVTQKDGEWWT--GSIGDRTGIFPSNYV 1055
Cdd:cd12011      3 VALCNFPSGGPTELSIRMGEQLTILSEDGDWWKvsSAVTGRECYIPSNYV 52

Src Homology 3 (SH3) domain of Inhibitor of ASPP protein (iASPP); iASPP, also called RelA-associated inhibitor (RAI), is an oncoprotein that inhibits the apoptotic transactivation potential of p53. It is upregulated in human breast cancers expressing wild-type p53, in acute leukemias regardless of the p53 mutation status, as well as in ovarian cancer where it is associated with poor patient outcome and chemoresistance. iASPP is also a binding partner and negative regulator of p65RelA, which promotes cell proliferation and inhibits apoptosis; p65RelA has the opposite effect on cell growth compared to the p53 family. It contains a proline-rich region, four ankyrin (ANK) repeats, and an SH3 domain at its C-terminal half. The SH3 domain and the ANK repeats of iASPP contribute to the p53 binding site; they bind to the DNA binding domain of p53. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212885 [Multi-domain] Cd Length: 56 Bit Score: 41.45 E-value: 1.06e-04

                           10        20        30        40
                   ....*....|....*....|....*....|....*....|....*....
gi 1804876928  787 ALYRFEARSHDEMSFNSGDIIQVDEKTIGEPGWLYGSFQGNFGWFPCNY 835
Cdd:cd11952      5 ALWDYSAEFPDELSFKEGDMVTVLRKDGEGTDWWWASLCGREGYVPRNY 53

Third Src homology 3 domain of ADAM-binding protein Eve-1; Eve-1, also called SH3 domain-containing protein 19 (SH3D19) or EEN-binding protein (EBP), exists in multiple alternatively spliced isoforms. The longest isoform contains five SH3 domain in the C-terminal region and seven proline-rich motifs in the N-terminal region. It is abundantly expressed in skeletal muscle and heart, and may be involved in regulating the activity of ADAMs (A disintegrin and metalloproteases). Eve-1 interacts with EEN, an endophilin involved in endocytosis and may be the target of the MLL-EEN fusion protein that is implicated in leukemogenesis. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212750 [Multi-domain] Cd Length: 51 Bit Score: 41.24 E-value: 1.08e-04

                           10        20        30        40
                   ....*....|....*....|....*....|....*....|....*....
gi 1804876928 1008 IALYSYSSVEPGDLTFIEGEEI-LVTQKDGEWWTGSIGDRTGIFPSNYV 1055
Cdd:cd11816      3 VARFDFEGEQEDELSFSEGDVItLKEYVGEEWAKGELNGKIGIFPLNFV 51

Second Src Homology 3 domain of FCH and double SH3 domains proteins; This group is composed of FCH and double SH3 domains protein 1 (FCHSD1) and FCHSD2. These proteins have a common domain structure consisting of an N-terminal F-BAR (FES-CIP4 Homology and Bin/Amphiphysin/Rvs), two SH3, and C-terminal proline-rich domains. They have only been characterized in silico and their functions remain unknown. This group also includes the insect protein, nervous wreck, which acts as a regulator of synaptic growth signaling. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212696 [Multi-domain] Cd Length: 57 Bit Score: 41.61 E-value: 1.09e-04

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|
gi 1804876928  924 AQALCSWTAKKDNHLNFSKHDIITVLEQQEN-----WWFGEVHGGRGWFP 968
Cdd:cd11762      2 VRALYDYEAQSDEELSFPEGAIIRILRKDDNgvddgWWEGEFNGRVGVFP 51

Src homology 3 domain of Hematopoietic lineage cell-specific protein 1; HS1, also called HCLS1 (hematopoietic cell-specific Lyn substrate 1), is a cortactin homolog expressed specifically in hematopoietic cells. It is an actin regulatory protein that binds the Arp2/3 complex and stabilizes branched actin filaments. It is required for cell spreading and signaling in lymphocytes. It regulates cytoskeletal remodeling that controls lymphocyte trafficking, and it also affects tissue invasion and infiltration of leukemic B cells. Like cortactin, HS1 contains an N-terminal acidic domain, several copies of a repeat domain found in cortactin and HS1, a proline-rich region, and a C-terminal SH3 domain. The N-terminal region binds the Arp2/3 complex and F-actin, while the C-terminal region acts as an adaptor or scaffold that can connect varied proteins that bind the SH3 domain within the actin network. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 213006 [Multi-domain] Cd Length: 55 Bit Score: 41.36 E-value: 1.10e-04

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|
gi 1804876928 1008 IALYSYSSVEPGDLTFIEGEEIL-VTQKDGEWWTGSIGDRTGIFPSNYVK 1056
Cdd:cd12073      4 VALYDYQGEGDDEISFDPQETITdIEMVDEGWWKGTCHGHRGLFPANYVE 53

Second Src homology 3 domain of Tyrosine kinase substrate (Tks) proteins; Tks proteins are Src substrates and scaffolding proteins that play important roles in the formation of podosomes and invadopodia, the dynamic actin-rich structures that are related to cell migration and cancer cell invasion. Vertebrates contain two Tks proteins, Tks4 (Tyr kinase substrate with four SH3 domains) and Tks5 (Tyr kinase substrate with five SH3 domains), which display partially overlapping but non-redundant functions. Both associate with the ADAMs family of transmembrane metalloproteases, which function as sheddases and mediators of cell and matrix interactions. Tks5 interacts with N-WASP and Nck, while Tks4 is essential for the localization of MT1-MMP (membrane-type 1 matrix metalloproteinase) to invadopodia. Tks proteins contain an N-terminal Phox homology (PX) domain and four or five SH3 domains. This model characterizes the second SH3 domain of Tks proteins. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212949 Cd Length: 54 Bit Score: 41.67 E-value: 1.11e-04

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|..
gi 1804876928 1152 QVIAMYDYVANNEDELNFSKGQLINVLNKDDPDWWQGEINGVTGLFPSNYVK 1203
Cdd:cd12016      2 KYITTQAYKAENEDEIGFETGVVVEVIQKNLDGWWKIRYQGKEGWAPATYLK 53

Src homology 3 domain of SH3 and multiple ankyrin repeat domains (Shank) proteins; Shank proteins carry scaffolding functions through multiple sites of protein-protein interaction in its domain architecture, including ankyrin (ANK) repeats, a long proline rich region, as well as SH3, PDZ, and SAM domains. They bind a variety of membrane and cytosolic proteins, and exist in alternatively spliced isoforms. They are highly enriched in postsynaptic density (PSD) where they interact with the cytoskeleton and with postsynaptic membrane receptors including NMDA and glutamate receptors. They are crucial in the construction and organization of the PSD and dendritic spines of excitatory synapses. There are three members of this family (Shank1, Shank2, Shank3) which show distinct and cell-type specific patterns of expression. Shank1 is brain-specific; Shank2 is found in neurons, glia, endocrine cells, liver, and kidney; Shank3 is widely expressed. The SH3 domain of Shank binds GRIP, a scaffold protein that binds AMPA receptors and Eph receptors/ligands. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212766 Cd Length: 50 Bit Score: 41.27 E-value: 1.20e-04

                           10        20        30        40
                   ....*....|....*....|....*....|....*....|....*...
gi 1804876928  785 YKALYRFEARSHDEMSFNSGDIIQVdeKTIGEPGWLYGSFQGNFGWFP 832
Cdd:cd11832      2 FIAVKSYSPQEEGEISLHKGDRVKV--LSIGEGGFWEGSVRGRTGWFP 47

Second Src homology 3 domain (or SH3B) of Intersectin; Intersectins (ITSNs) are adaptor proteins that function in exo- and endocytosis, actin cytoskeletal reorganization, and signal transduction. They are essential for initiating clathrin-coated pit formation. They bind to many proteins through their multidomain structure and facilitate the assembly of multimeric complexes. Vertebrates contain two ITSN proteins, ITSN1 and ITSN2, which exist in alternatively spliced short and long isoforms. The short isoforms contain two Eps15 homology domains (EH1 and EH2), a coiled-coil region and five SH3 domains (SH3A-E), while the long isoforms, in addition, contain RhoGEF (also called Dbl-homologous or DH), Pleckstrin homology (PH) and C2 domains. ITSN1 and ITSN2 are both widely expressed, with variations depending on tissue type and stage of development. The second SH3 domain (or SH3B) of ITSN1 has been shown to bind WNK and CdGAP. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212771 [Multi-domain] Cd Length: 53 Bit Score: 41.20 E-value: 1.21e-04

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....*...
gi 1804876928 1080 QVTSAYV--ASGSEQLSLAPGQLILILKKNSSgWWQGELQargkKRQKGWFPASHVKL 1135
Cdd:cd11837      1 TATALYPwrAKKENHLSFAKGDIITVLEQQEM-WWFGELE----GGEEGWFPKSYVKE 53

Src homology 3 domain of Cortactin; Cortactin was originally identified as a substrate of Src kinase. It is an actin regulatory protein that binds to the Arp2/3 complex and stabilizes branched actin filaments. It is involved in cellular processes that affect cell motility, adhesion, migration, endocytosis, and invasion. It is expressed ubiquitously except in hematopoietic cells, where the homolog hematopoietic lineage cell-specific 1 (HS1) is expressed instead. Cortactin contains an N-terminal acidic domain, several copies of a repeat domain found in cortactin and HS1, a proline-rich region, and a C-terminal SH3 domain. The N-terminal region interacts with the Arp2/3 complex and F-actin, and is crucial in regulating branched actin assembly. Cortactin also serves as a scaffold and provides a bridge to the actin cytoskeleton for membrane trafficking and signaling proteins that bind to its SH3 domain. Binding partners for the SH3 domain of cortactin include dynamin2, N-WASp, MIM, FGD1, among others. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212892 [Multi-domain] Cd Length: 53 Bit Score: 41.25 E-value: 1.23e-04

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|
gi 1804876928 1008 IALYSYSSVEPGDLTFIEGEEIL-VTQKDGEWWTGSIGDRTGIFPSNYVK 1056
Cdd:cd11959      3 VALYDYQAADDDEISFDPDDIITnIEMIDEGWWRGVCRGKYGLFPANYVE 52

Src homology 3 domain of CAS (Crk-Associated Substrate) scaffolding protein family member, Neural precursor cell Expressed, Developmentally Down-regulated 9; NEDD9 is also called human enhancer of filamentation 1 (HEF1) or CAS-L (Crk-associated substrate in lymphocyte). It was first described as a gene predominantly expressed in early embryonic brain, and was also isolated from a screen of human proteins that regulate filamentous budding in yeast, and as a tyrosine phosphorylated protein in lymphocytes. It promotes metastasis in different solid tumors. NEDD9 localizes in focal adhesions and associates with FAK and Abl kinase. It also interacts with SMAD3 and the proteasomal machinery which allows its rapid turnover; these interactions are not shared by other CAS proteins. CAS proteins function as molecular scaffolds to regulate protein complexes that are involved in many cellular processes. They share a common domain structure that includes an N-terminal SH3 domain, an unstructured substrate domain that contains many YxxP motifs, a serine-rich four-helix bundle, and a FAT-like C-terminal domain. The SH3 domain of CAS proteins binds to diverse partners including FAK, FRNK, Pyk2, PTP-PEST, DOCK180, among others. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212935 Cd Length: 57 Bit Score: 41.51 E-value: 1.23e-04

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....*.
gi 1804876928  924 AQALCSWTAKKDNHLNFSKHDIITVLEQQ----ENWWFGEVHGGRGWFPKSYVKII 975
Cdd:cd12002      2 ARALYDNVPECAEELAFRKGDILTVIEQNtgglEGWWLCSLHGRQGIAPGNRLKLL 57

recombination and DNA strand exchange inhibitor protein; Reviewed

Pssm-ID: 234750 [Multi-domain] Cd Length: 782 Bit Score: 46.74 E-value: 1.28e-04

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1804876928  404 KANYERGNVELEKRRQALmEQQQREAE---RKAQKEKEEWERKQRELQEQEWKKQLELEKRLEKQrelerqreeeRRKEI 480
Cdd:PRK00409   508 KKLIGEDKEKLNELIASL-EELERELEqkaEEAEALLKEAEKLKEELEEKKEKLQEEEDKLLEEA----------EKEAQ 576

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1804876928  481 ERREAAKQELERQRRlEWERIRRQELLNQRNREQEEivrlnsKKKSLHLELEALNgKHQQISGRLQD-------VRLRKQ 553
Cdd:PRK00409   577 QAIKEAKKEADEIIK-ELRQLQKGGYASVKAHELIE------ARKRLNKANEKKE-KKKKKQKEKQEelkvgdeVKYLSL 648

                          170       180
                   ....*....|....*....|....*
gi 1804876928  554 TQKTEI-EVLDK---QCDLEIMEIK 574
Cdd:PRK00409   649 GQKGEVlSIPDDkeaIVQAGIMKMK 673

Src Homology 3 domain of Brain-specific Angiogenesis Inhibitor 1-Associated Protein 2-Like 1, also called Insulin Receptor Tyrosine Kinase Substrate (IRTKS); BAIAP2L1 or IRTKS is widely expressed, serves as a substrate for the insulin receptor, and binds the small GTPase Rac. It plays a role in regulating the actin cytoskeleton and colocalizes with F-actin, cortactin, VASP, and vinculin. BAIAP2L1 expression leads to the formation of short actin bundles, distinct from filopodia-like protrusions induced by the expression of the related protein IRSp53. IRTKS mediates the recruitment of effector proteins Tir and EspFu, which regulate host cell actin reorganization, to bacterial attachment sites. It contains an N-terminal IMD or Inverse-Bin/Amphiphysin/Rvs (I-BAR) domain, an SH3 domain, and a WASP homology 2 (WH2) actin-binding motif at the C-terminus. The SH3 domain of IRTKS has been shown to bind the proline-rich C-terminus of EspFu. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212846 Cd Length: 58 Bit Score: 41.44 E-value: 1.31e-04

                           10        20        30        40
                   ....*....|....*....|....*....|....*....|
gi 1804876928  938 LNFSKHDIITVL--EQQENWWFGE--VHGGRGWFPKSYVK 973
Cdd:cd11913     18 LSFAQGDVITLLipEEKDGWLYGEhdTTKARGWFPSSYTR 57

Variant SH3 domain;

Pssm-ID: 434066 [Multi-domain] Cd Length: 49 Bit Score: 41.06 E-value: 1.31e-04

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|.
gi 1804876928 1084 AYVASGSEQLSLAPGQLILILKKNSSGWWQGELQARgkkrqKGWFPASHVK 1134
Cdd:pfam14604    4 PYEPKDDDELSLQRGDVITVIEESEDGWWEGINTGR-----TGLVPANYVE 49

Membrane protein TolA involved in colicin uptake [Cell wall/membrane/envelope biogenesis];

Pssm-ID: 442298 [Multi-domain] Cd Length: 485 Bit Score: 46.57 E-value: 1.33e-04

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1804876928  384 QKIQEEEPQKKLPVtfEDKRKANYERgnvelEKRRQALMEQQqREAERKAQKEKEEWERKQRELQEQEWKKQLELEKRLE 463
Cdd:COG3064     16 ERLEQAEAEKRAAA--EAEQKAKEEA-----EEERLAELEAK-RQAEEEAREAKAEAEQRAAELAAEAAKKLAEAEKAAA 87

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1804876928  464 KqrelerqreeerRKEIERREAAKQELERQRRLEWERIR---RQELLNQRNREQEEIVRLNSKKKSLHLELEALNGKHQQ 540
Cdd:COG3064     88 E------------AEKKAAAEKAKAAKEAEAAAAAEKAAaaaEKEKAEEAKRKAEEEAKRKAEEERKAAEAEAAAKAEAE 155

                          170
                   ....*....|....*...
gi 1804876928  541 ISGRLQDVRLRKQTQKTE 558
Cdd:COG3064    156 AARAAAAAAAAAAAAAAR 173

Second Src Homology 3 domain of Bzz1 and similar domains; Bzz1 (or Bzz1p) is a WASP/Las17-interacting protein involved in endocytosis and trafficking to the vacuole. It physically interacts with type I myosins and functions in the early steps of endocytosis. Together with other proteins, it induces membrane scission in yeast. Bzz1 contains an N-terminal F-BAR (FES-CIP4 Homology and Bin/Amphiphysin/Rvs), a central coiled-coil, and two C-terminal SH3 domains. This model represents the second C-terminal SH3 domain. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212712 [Multi-domain] Cd Length: 51 Bit Score: 41.33 E-value: 1.34e-04

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|.
gi 1804876928  923 KAQALCSWTAKKDNHLNFSKHDIITVLEQQEN--WWFGEVHGGRGWFPKSY 971
Cdd:cd11778      1 YVEALYDYEAQGDDEISIRVGDRIAVIRGDDGsgWTYGEINGVKGLFPTSY 51

Src homology 3 domain of Proline-Serine-Threonine Phosphatase-Interacting Protein 1; PSTPIP1, also called CD2 Binding Protein 1 (CD2BP1), is mainly expressed in hematopoietic cells. It is a binding partner of the cell surface receptor CD2 and PTP-PEST, a tyrosine phosphatase which functions in cell motility and Rac1 regulation. It also plays a role in the activation of the Wiskott-Aldrich syndrome protein (WASP), which couples actin rearrangement and T cell activation. Mutations in the gene encoding PSTPIP1 cause the autoinflammatory disorder known as PAPA (pyogenic sterile arthritis, pyoderma gangrenosum, and acne) syndrome. PSTPIP1 contains an N-terminal F-BAR domain, PEST motifs, and a C-terminal SH3 domain. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212758 [Multi-domain] Cd Length: 53 Bit Score: 41.20 E-value: 1.34e-04

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|..
gi 1804876928 1006 EYIALYSYSSVEPGDLTFIEGEEILVTQKDGE-WWTGSIGDRTGIFPSNYVK 1056
Cdd:cd11824      1 KYSVLYDYTAQEDDELSISKGDVVAVIEKGEDgWWTVERNGQKGLVPGTYLE 52

Src homology 3 domain of Signal Transducing Adaptor Molecule 2; STAM2, also called EAST (Epidermal growth factor receptor-associated protein with SH3 and TAM domain) or Hbp (Hrs binding protein), is part of the endosomal sorting complex required for transport (ESCRT-0). It plays a role in sorting mono-ubiquinated endosomal cargo for trafficking to the lysosome for degradation. It is also involved in the regulation of exocytosis. STAMs were discovered as proteins that are highly phosphorylated following cytokine and growth factor stimulation. They function in cytokine signaling and surface receptor degradation, as well as regulate Golgi morphology. They associate with many proteins including Jak2 and Jak3 tyrosine kinases, Hrs, AMSH, and UBPY. STAM adaptor proteins contain VHS (Vps27, Hrs, STAM homology), ubiquitin interacting (UIM), and SH3 domains. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212896 [Multi-domain] Cd Length: 57 Bit Score: 41.54 E-value: 1.38e-04

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|.
gi 1804876928  786 KALYRFEARSHDEMSFNSGDIIQVDEKTigEPGWLYGSFQGNFGWFPCNYV 836
Cdd:cd11963      5 RALYDFEAVEDNELTFKHGEIIIVLDDS--DANWWKGENHRGVGLFPSNFV 53

Src homology 3 domain of Proline-Serine-Threonine Phosphatase-Interacting Protein 1; PSTPIP1, also called CD2 Binding Protein 1 (CD2BP1), is mainly expressed in hematopoietic cells. It is a binding partner of the cell surface receptor CD2 and PTP-PEST, a tyrosine phosphatase which functions in cell motility and Rac1 regulation. It also plays a role in the activation of the Wiskott-Aldrich syndrome protein (WASP), which couples actin rearrangement and T cell activation. Mutations in the gene encoding PSTPIP1 cause the autoinflammatory disorder known as PAPA (pyogenic sterile arthritis, pyoderma gangrenosum, and acne) syndrome. PSTPIP1 contains an N-terminal F-BAR domain, PEST motifs, and a C-terminal SH3 domain. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212758 [Multi-domain] Cd Length: 53 Bit Score: 41.20 E-value: 1.38e-04

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....*..
gi 1804876928 1079 AQVTSAYVASGSEQLSLAPGQLILILKKNSSGWWQGElqargKKRQKGWFPASHVKL 1135
Cdd:cd11824      2 YSVLYDYTAQEDDELSISKGDVVAVIEKGEDGWWTVE-----RNGQKGLVPGTYLEK 53

Ca2+-binding protein, EF-hand superfamily [Signal transduction mechanisms];

Pssm-ID: 444056 [Multi-domain] Cd Length: 137 Bit Score: 43.63 E-value: 1.38e-04

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....*....
gi 1804876928  285 RQKFNSLDKSMSGYLSGFQARNALLQSNLSQTQLATIWTLADIDGDGQLRAEEFILAMH 343
Cdd:COG5126     72 RAAFDLLDTDGDGKISADEFRRLLTALGVSEEEADELFARLDTDGDGKISFEEFVAAVR 130

Third N-terminal Src homology 3 domain of Dynamin Binding Protein, also called Tuba; DNMBP or Tuba is a cdc42-specific guanine nucleotide exchange factor (GEF) that contains four N-terminal SH3 domains, a central RhoGEF [or Dbl homology (DH)] domain followed by a Bin/Amphiphysin/Rvs (BAR) domain, and two C-terminal SH3 domains. It provides a functional link between dynamin and key regulatory proteins of the actin cytoskeleton. It plays an important role in regulating cell junction configuration. The four N-terminal SH3 domains of DNMBP binds the GTPase dynamin, which plays an important role in the fission of endocytic vesicles. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212730 Cd Length: 51 Bit Score: 41.19 E-value: 1.38e-04

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|.
gi 1804876928  786 KALYRFEARSHDEMSFNSGDIIQVDEktIGEPGWLYGSFQGNFGWFPCNYV 836
Cdd:cd11796      3 RVLQDLSAQLDEELDLREGDVVTITG--ILDKGWFRGELNGRRGIFPEGFV 51

Src homology 3 domain of Slit-Robo GTPase Activating Protein 4; srGAP4, also called ARHGAP4, is highly expressed in hematopoietic cells and may play a role in lymphocyte differentiation. It is able to stimulate the GTPase activity of Rac1, Cdc42, and RhoA. In the nervous system, srGAP4 has been detected in differentiating neurites and may be involved in axon and dendritic growth. srGAPs are Rho GAPs that interact with Robo1, the transmembrane receptor of Slit proteins. Slit proteins are secreted proteins that control axon guidance and the migration of neurons and leukocytes. srGAPs contain an N-terminal F-BAR domain, a Rho GAP domain, and a C-terminal SH3 domain. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212889 [Multi-domain] Cd Length: 55 Bit Score: 41.36 E-value: 1.40e-04

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|.
gi 1804876928 1006 EYIALYSYSSVEPGDLTFIEGEEILVTQK-DGEWWTGSIGDRTGIFPSNYV 1055
Cdd:cd11956      3 EAVACFDYTGRTAQELSFKRGDVLLLHSKaSSDWWRGEHNGMRGLIPHKYI 53

Src homology 3 domain of ArfGAP with SH3 domain, ankyrin repeat and PH domain containing proteins; ASAPs are Arf GTPase activating proteins (GAPs) and they function in regulating cell growth, migration, and invasion. They contain an N-terminal BAR domain, followed by a Pleckstrin homology (PH) domain, an Arf GAP domain, ankyrin (ANK) repeats, and a C-terminal SH3 domain. Vertebrates contain at least three members, ASAP1, ASAP2, and ASAP3, but some ASAP3 proteins do not seem to harbor a C-terminal SH3 domain. ASAP1 and ASAP2 show GTPase activating protein (GAP) activity towards Arf1 and Arf5. They do not show GAP activity towards Arf6, but are able to mediate Arf6 signaling by binding stably to GTP-Arf6. ASAP3 is an Arf6-specific GAP. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212755 [Multi-domain] Cd Length: 53 Bit Score: 41.15 E-value: 1.42e-04

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|...
gi 1804876928  923 KAQALCSWTAKKDNHLNFSKHDIITVL-EQQENWWFGEVHGG---RGWFPKSY 971
Cdd:cd11821      1 RVRALYDCQADNDDELTFSEGEIIVVTgEEDDEWWEGHIEGDpsrRGVFPVSF 53

First Src Homology 3 domain of Sorbin and SH3 domain containing 1 (Sorbs1), also called ponsin; Sorbs1 is also called ponsin, SH3P12, or CAP (c-Cbl associated protein). It is an adaptor protein containing one sorbin homology (SoHo) and three SH3 domains. It binds Cbl and plays a major role in regulating the insulin signaling pathway by enhancing insulin-induced phosphorylation of Cbl. Sorbs1, like vinexin, localizes at cell-ECM and cell-cell adhesion sites where it binds vinculin, paxillin, and afadin. It may function in the control of cell motility. Other interaction partners of Sorbs1 include c-Abl, Sos, flotillin, Grb4, ataxin-7, filamin C, among others. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212852 [Multi-domain] Cd Length: 55 Bit Score: 41.10 E-value: 1.47e-04

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....
gi 1804876928  923 KAQALCSWTAKKDNHLNFSKHDIITVLEQ-QENWWFGEVHGGRGWFPKSYVKII 975
Cdd:cd11919      2 PARAKFDFKAQTLKELPLQKGDIVYIYKQiDQNWYEGEHHGRVGIFPRSYIELL 55

Src homology 3 domain of Hematopoietic lineage cell-specific protein 1; HS1, also called HCLS1 (hematopoietic cell-specific Lyn substrate 1), is a cortactin homolog expressed specifically in hematopoietic cells. It is an actin regulatory protein that binds the Arp2/3 complex and stabilizes branched actin filaments. It is required for cell spreading and signaling in lymphocytes. It regulates cytoskeletal remodeling that controls lymphocyte trafficking, and it also affects tissue invasion and infiltration of leukemic B cells. Like cortactin, HS1 contains an N-terminal acidic domain, several copies of a repeat domain found in cortactin and HS1, a proline-rich region, and a C-terminal SH3 domain. The N-terminal region binds the Arp2/3 complex and F-actin, while the C-terminal region acts as an adaptor or scaffold that can connect varied proteins that bind the SH3 domain within the actin network. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 213006 [Multi-domain] Cd Length: 55 Bit Score: 41.36 E-value: 1.47e-04

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|..
gi 1804876928 1085 YVASGSEQLSLAPGQLILILKKNSSGWWQGelQARGKkrqKGWFPASHVKLL 1136
Cdd:cd12073      9 YQGEGDDEISFDPQETITDIEMVDEGWWKG--TCHGH---RGLFPANYVELL 55

Fourth N-terminal Src homology 3 domain of Dynamin Binding Protein, also called Tuba; DNMBP or Tuba is a cdc42-specific guanine nucleotide exchange factor (GEF) that contains four N-terminal SH3 domains, a central RhoGEF [or Dbl homology (DH)] domain followed by a Bin/Amphiphysin/Rvs (BAR) domain, and two C-terminal SH3 domains. It provides a functional link between dynamin and key regulatory proteins of the actin cytoskeleton. It plays an important role in regulating cell junction configuration. The four N-terminal SH3 domains of DNMBP bind the GTPase dynamin, which plays an important role in the fission of endocytic vesicles. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212731 Cd Length: 50 Bit Score: 40.87 E-value: 1.49e-04

                           10        20        30        40
                   ....*....|....*....|....*....|....*....|....*.
gi 1804876928  787 ALYRFEARSHDEMSFNSGDIIQVdeKTIGEPGWLYGSFQGNFGWFP 832
Cdd:cd11797      4 ALYRFQALEPNELDFEVGDRIRI--IATLEDGWLEGELKGRRGIFP 47

Src homology 3 domain of Protein kinase C and Casein kinase Substrate in Neurons 3 (PACSIN3); PACSIN 3 or Syndapin III (Synaptic dynamin-associated protein III) is expressed ubiquitously and regulates glucose uptake in adipocytes through its role in GLUT1 trafficking. It also modulates the subcellular localization and stimulus-specific function of the cation channel TRPV4. PACSINs act as regulators of cytoskeletal and membrane dynamics. Vetebrates harbor three isoforms with distinct expression patterns and specific functions. PACSINs contain an N-terminal F-BAR domain and a C-terminal SH3 domain. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212930 [Multi-domain] Cd Length: 56 Bit Score: 41.10 E-value: 1.51e-04

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|.
gi 1804876928 1009 ALYSYSSVEPGDLTFIEGEEILVTQKDGE--WWTGSI-GDRTGIFPSNYVK 1056
Cdd:cd11997      6 ALYDYTGQEADELSFKAGEELLKIGEEDEqgWCKGRLlSGRIGLYPANYVE 56

First Src Homology 3 domain of FCH and double SH3 domains proteins; This group is composed of FCH and double SH3 domains protein 1 (FCHSD1) and FCHSD2. These proteins have a common domain structure consisting of an N-terminal F-BAR (FES-CIP4 Homology and Bin/Amphiphysin/Rvs), two SH3, and C-terminal proline-rich domains. They have only been characterized in silico and their functions remain unknown. This group also includes the insect protein, nervous wreck, which acts as a regulator of synaptic growth signaling. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212695 [Multi-domain] Cd Length: 57 Bit Score: 41.19 E-value: 1.54e-04

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....
gi 1804876928 1151 CQVIamYDYVANNEDELNFSKGQLINVLNKDDPDWWQGEIN--GVTGLFPSNYV 1202
Cdd:cd11761      4 CKVL--YSYEAQRPDELTITEGEELEVIEDGDGDGWVKARNksGEVGYVPENYL 55

Second Src Homology 3 domain (SH3B) of CD2-associated protein and similar proteins; This subfamily is composed of the second SH3 domain (SH3B) of CD2AP, CIN85 (Cbl-interacting protein of 85 kDa), and similar domains. CD2AP and CIN85 are adaptor proteins that bind to protein partners and assemble complexes that have been implicated in T cell activation, kidney function, and apoptosis of neuronal cells. They also associate with endocytic proteins, actin cytoskeleton components, and other adaptor proteins involved in receptor tyrosine kinase (RTK) signaling. CD2AP and the main isoform of CIN85 contain three SH3 domains, a proline-rich region, and a C-terminal coiled-coil domain. All of these domains enable CD2AP and CIN85 to bind various protein partners and assemble complexes that have been implicated in many different functions. SH3B of both proteins have been shown to bind to Cbl. In the case of CD2AP, its SH3B binds to Cbl at a site distinct from the c-Cbl/SH3A binding site. The CIN85 SH3B also binds ubiquitin. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212807 [Multi-domain] Cd Length: 53 Bit Score: 41.17 E-value: 1.57e-04

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|...
gi 1804876928  923 KAQALCSWTAKKDNHLNFSKHDIITVLEQ-QENWWFGEVHGGRGWFPKSYVKI 974
Cdd:cd11874      1 RCKVLFSYTPQNEDELELKVGDTIEVLGEvEEGWWEGKLNGKVGVFPSNFVKE 53

Src Homology 3 domain of beta-Pak Interactive eXchange factor; Beta-PIX, also called Rho guanine nucleotide exchange factor 7 (ARHGEF7) or Cool (Cloned out of Library)-1, activates small GTPases by exchanging bound GDP for free GTP. It acts as a GEF for both Cdc42 and Rac 1, and plays important roles in regulating neuroendocrine exocytosis, focal adhesion maturation, cell migration, synaptic vesicle localization, and insulin secretion. PIX proteins contain an N-terminal SH3 domain followed by RhoGEF (also called Dbl-homologous or DH) and Pleckstrin Homology (PH) domains, and a C-terminal leucine-zipper domain for dimerization. The SH3 domain of PIX binds to an atypical PxxxPR motif in p21-activated kinases (PAKs) with high affinity. The binding of PAKs to PIX facilitate the localization of PAKs to focal complexes and also localizes PAKs to PIX targets Cdc43 and Rac, leading to the activation of PAKs. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212994 [Multi-domain] Cd Length: 54 Bit Score: 41.21 E-value: 1.60e-04

                           10        20        30        40
                   ....*....|....*....|....*....|....*....|....*..
gi 1804876928 1088 SGSEQLSLAPGQLILILKKNSSGWWQGELQARgkkrqKGWFPASHVK 1134
Cdd:cd12061     11 TNEDELSFSKGDVIHVTRVEEGGWWEGTHNGR-----TGWFPSNYVR 52

First Src Homology 3 domain (SH3A) of Cbl-interacting protein of 85 kDa; CIN85, also called SH3 domain-containing kinase-binding protein 1 (SH3KBP1) or CD2-binding protein 3 (CD2BP3) or Ruk, is an adaptor protein that is involved in the downregulation of receptor tyrosine kinases by facilitating endocytosis through interaction with endophilin-associated ubiquitin ligase Cbl proteins. It is also important in many other cellular processes including vesicle-mediated transport, cytoskeletal remodelling, apoptosis, cell adhesion and migration, and viral infection, among others. CIN85 exists as multiple variants from alternative splicing; the main variant contains three SH3 domains, a proline-rich region, and a C-terminal coiled-coil domain. All of these domains enable CIN85 to bind various protein partners and assemble complexes that have been implicated in many different functions. This alignment model represents the first SH3 domain (SH3A) of CIN85; SH3A binds to internal proline-rich motifs within the proline-rich region. This intramolecular interaction serves as a regulatory mechanism to keep CIN85 in a closed conformation, preventing the recruitment of other proteins. SH3A has also been shown to bind ubiquitin and to an atypical PXXXPR motif at the C-terminus of Cbl and the cytoplasmic end of the cell adhesion protein CD2. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212985 [Multi-domain] Cd Length: 53 Bit Score: 41.03 E-value: 1.62e-04

                           10        20        30        40
                   ....*....|....*....|....*....|....*....|....*
gi 1804876928  930 WTAKKDNHLNFSKHDIITVLEQQEN-WWFGEVHGGRGWFPKSYVK 973
Cdd:cd12052      8 YKAQHEDELTITVGDIITKIKKDDGgWWEGEIKGRRGLFPDNFVR 52

First Src Homology 3 domain of Vinexin, also called Sorbin and SH3 domain containing 3 (Sorbs3); Vinexin is also called Sorbs3, SH3P3, and SH3-containing adapter molecule 1 (SCAM-1). It is an adaptor protein containing one sorbin homology (SoHo) and three SH3 domains. Vinexin was first identified as a vinculin binding protein; it is co-localized with vinculin at cell-ECM and cell-cell adhesion sites. There are several splice variants of vinexin: alpha, which contains the SoHo and three SH3 domains and displays tissue-specific expression; and beta, which contains only the three SH3 domains and is widely expressed. Vinexin alpha stimulates the accumulation of F-actin at focal contact sites. Vinexin also promotes keratinocyte migration and wound healing. The SH3 domains of vinexin have been reported to bind a number of ligands including vinculin, WAVE2, DLG5, Abl, and Cbl. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212854 Cd Length: 55 Bit Score: 41.06 E-value: 1.64e-04

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|
gi 1804876928 1155 AMYDYVANNEDELNFSKGQLINVLNKDDPDWWQGEINGVTGLFPSNYVKM 1204
Cdd:cd11921      5 LKFDFQAQSPKELTLQKGDIVYIHKEVDKNWLEGEHHGRVGIFPANYVEV 54

Src Homology 3 domain of fungal peroxisomal membrane protein Pex13p; Pex13p, located in the peroxisomal membrane, contains two transmembrane regions and a C-terminal SH3 domain. It binds to the peroxisomal targeting type I (PTS1) receptor Pex5p and the docking factor Pex14p through its SH3 domain. It is essential for both PTS1 and PTS2 protein import pathways into the peroxisomal matrix. Pex13p binds Pex14p, which contains a PxxP motif, in a classical fashion to the proline-rich ligand binding site of its SH3 domain. It binds the WxxxF/Y motif of Pex5p in a novel site that does not compete with Pex14p binding. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212705 [Multi-domain] Cd Length: 60 Bit Score: 41.11 E-value: 1.64e-04

                           10        20        30        40
                   ....*....|....*....|....*....|....*....|....*...
gi 1804876928 1091 EQLSLAPGQLILILKK-----NSSGWWQGelqaRGKKRQKGWFPASHV 1133
Cdd:cd11771     15 MELSLKKGDIVAVLSKtdplgRDSEWWKG----RTRDGRIGWFPSNYV 58

First Src Homology 3 domain of Sorbin and SH3 domain containing (Sorbs) proteins and similar domains; This family, also called the vinexin family, is composed predominantly of adaptor proteins containing one sorbin homology (SoHo) and three SH3 domains. Members include the first SH3 domains of Sorbs1 (or ponsin), Sorbs2 (or ArgBP2), Vinexin (or Sorbs3), and similar domains. They are involved in the regulation of cytoskeletal organization, cell adhesion, and growth factor signaling. Members of this family bind multiple partners including signaling molecules like c-Abl, c-Arg, Sos, and c-Cbl, as well as cytoskeletal molecules such as vinculin and afadin. They may have overlapping functions. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212715 [Multi-domain] Cd Length: 53 Bit Score: 40.79 E-value: 1.65e-04

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|.
gi 1804876928 1008 IALYSYSSVEPGDLTFIEGEEILVTQK-DGEWWTGSIGDRTGIFPSNYVKP 1057
Cdd:cd11781      3 RALYPFKAQSAKELSLKKGDIIYIRRQiDKNWYEGEHNGRVGIFPASYVEI 53

Third Src Homology 3 domain of Nck adaptor proteins; This group contains the third SH3 domain of Nck, the first SH3 domain of Caenorhabditis elegans Ced-2 (Cell death abnormality protein 2), and similar domains. Nck adaptor proteins regulate actin cytoskeleton dynamics by linking proline-rich effector molecules to protein tyrosine kinases and phosphorylated signaling intermediates. They contain three SH3 domains and a C-terminal SH2 domain. They function downstream of the PDGFbeta receptor and are involved in Rho GTPase signaling and actin dynamics. Vertebrates contain two Nck adaptor proteins: Nck1 (also called Nckalpha) and Nck2 (also called Nckbeta or Growth factor receptor-bound protein 4, Grb4), which show partly overlapping functions but also bind distinct targets. Their SH3 domains are involved in recruiting downstream effector molecules, such as the N-WASP/Arp2/3 complex, which when activated induces actin polymerization that results in the production of pedestals, or protrusions of the plasma membrane. The third SH3 domain of Nck appears to prefer ligands with a PxAPxR motif. SH3 domains are protein interaction domains that usually bind to proline-rich ligands with moderate affinity and selectivity, preferentially a PxxP motif. Ced-2 is a cell corpse engulfment protein that interacts with Ced-5 in a pathway that regulates the activation of Ced-10, a Rac small GTPase.

Pssm-ID: 212701 [Multi-domain] Cd Length: 56 Bit Score: 41.14 E-value: 1.77e-04

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|..
gi 1804876928  787 ALYRFEARSHDEMSFNSGDIIQVDEKTIGEPGWLYG-SFQGNFGWFPCNYVE 837
Cdd:cd11767      4 ALYPFTGENDEELSFEKGERLEIIEKPEDDPDWWKArNALGTTGLVPRNYVE 55

Src Homology 3 domain of Mixed Lineage Kinases 1, 2, and 3; MLKs 1, 2, and 3 are Serine/Threonine Kinases (STKs), catalyzing the transfer of the gamma-phosphoryl group from ATP to S/T residues on protein substrates. MLKs act as mitogen-activated protein kinase kinase kinases (MAP3Ks, MKKKs, MAPKKKs), which phosphorylate and activate MAPK kinases (MAPKKs or MKKs or MAP2Ks), which in turn phosphorylate and activate MAPKs during signaling cascades that are important in mediating cellular responses to extracellular signals. MLKs play roles in immunity and inflammation, as well as in cell death, proliferation, and cell cycle regulation. Little is known about the specific function of MLK1, also called MAP3K9. It is capable of activating the c-Jun N-terminal kinase pathway. Mice lacking both MLK1 and MLK2 are viable, fertile, and have normal life spans. MLK2, also called MAP3K10, is abundant in brain, skeletal muscle, and testis. It functions upstream of the MAPK, c-Jun N-terminal kinase. It binds hippocalcin, a calcium-sensor protein that protects neurons against calcium-induced cell death. Both MLK2 and hippocalcin may be associated with the pathogenesis of Parkinson's disease. MLK3, also called MAP3K11, is highly expressed in breast cancer cells and its signaling through c-Jun N-terminal kinase has been implicated in the migration, invasion, and malignancy of cancer cells. It also functions as a negative regulator of Inhibitor of Nuclear Factor-KappaB Kinase (IKK) and thus, impacts inflammation and immunity. MLKs contain an SH3 domain, a catalytic kinase domain, a leucine zipper, a proline-rich region, and a CRIB domain that mediates binding to GTP-bound Cdc42 and Rac. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212992 [Multi-domain] Cd Length: 58 Bit Score: 40.91 E-value: 1.78e-04

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....
gi 1804876928 1085 YVASGSEQLSLAPGQLILILKKNSS-----GWWQGELQARgkkrqKGWFPASHV 1133
Cdd:cd12059      8 YEASAEDELTLRRGDRVEVLSKDSAvsgdeGWWTGKINDR-----VGIFPSNYV 56

First Src Homology 3 domain of the fungal endocytic adaptor protein Sla1p; Sla1p facilitates endocytosis by playing a role as an adaptor protein in coupling components of the actin cytoskeleton to the endocytic machinery. It interacts with Abp1p, Las17p and Pan1p, which are activator proteins of actin-related protein 2/3 (Arp2/3). Sla1p contains multiple domains including three SH3 domains, a SAM (sterile alpha motif) domain, and a Sla1 homology domain 1 (SHD1), which binds to the NPFXD motif that is found in many integral membrane proteins such as the Golgi-localized Arf-binding protein Lsb5p and the P4-ATPases, Drs2p and Dnf1p. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212707 [Multi-domain] Cd Length: 57 Bit Score: 40.87 E-value: 1.82e-04

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....*.
gi 1804876928 1007 YIALYSYSSVEPGDLTFIEGEEILVTQK-DGEWWT----GSIGDRT---GIFPSNY 1054
Cdd:cd11773      2 YKALYDYEPQTEDELTIQEDDILYLLEKsDDDWWKvklkVNSSDDDepvGLVPATY 57

Src homology 3 domain of an unknown subfamily of proteins with similarity to Protein kinase C and Casein kinase Substrate in Neurons (PACSIN) proteins; PACSINs, also called Synaptic dynamin-associated proteins (Syndapins), act as regulators of cytoskeletal and membrane dynamics. They bind both dynamin and Wiskott-Aldrich syndrome protein (WASP), and may provide direct links between the actin cytoskeletal machinery through WASP and dynamin-dependent endocytosis. Vetebrates harbor three isoforms with distinct expression patterns and specific functions. PACSINs contain an N-terminal F-BAR domain and a C-terminal SH3 domain. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212932 [Multi-domain] Cd Length: 56 Bit Score: 41.08 E-value: 1.83e-04

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....*..
gi 1804876928  783 VNYKALYRFEARSHDEMSFNSGD-IIQVDEKTigEPGWLYG-SFQGNFGWFPCNYVE 837
Cdd:cd11999      2 VRVRAVYDYTGQEPDELSFKAGEeLLKVEDED--EQGWCKGvTDGGAVGLYPANYVE 56

Src homology 3 domain of the Rho guanine nucleotide exchange factor ARHGEF9; ARHGEF9, also called PEM2 or collybistin, selectively activates Cdc42 by exchanging bound GDP for free GTP. It is highly expressed in the brain and it interacts with gephyrin, a postsynaptic protein associated with GABA and glycine receptors. Mutations in the ARHGEF9 gene cause X-linked mental retardation with associated features like seizures, hyper-anxiety, aggressive behavior, and sensory hyperarousal. ARHGEF9 contains a SH3 domain followed by RhoGEF (also called Dbl-homologous or DH) and Pleckstrin Homology (PH) domains. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212908 Cd Length: 62 Bit Score: 41.23 E-value: 1.86e-04

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....
gi 1804876928  922 LKAQALCSWTAKKDNHLNFSKHDIITVLE-QQENWWFGEVHGGRGWFPKSYVKI 974
Cdd:cd11975      5 VSAEAVWDHVTMANRELAFKAGDVIKVLDaSNKDWWWGQIDDEEGWFPASFVRL 58

Src homology 3 domain of SH3 protein interacting with Nck, 90 kDa (SPIN90); SPIN90 is also called NCK interacting protein with SH3 domain (NCKIPSD), Dia-interacting protein (DIP), 54 kDa vimentin-interacting protein (VIP54), or WASP-interacting SH3-domain protein (WISH). It is an F-actin binding protein that regulates actin polymerization and endocytosis. It associates with the Arp2/3 complex near actin filaments and determines filament localization at the leading edge of lamellipodia. SPIN90 is expressed in the early stages of neuronal differentiation and plays a role in regulating growth cone dynamics and neurite outgrowth. It also interacts with IRSp53 and regulates cell motility by playing a role in the formation of membrane protrusions. SPIN90 contains an N-terminal SH3 domain, a proline-rich domain, and a C-terminal VCA (verprolin-homology and cofilin-like acidic) domain. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212783 [Multi-domain] Cd Length: 53 Bit Score: 40.76 E-value: 1.88e-04

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|
gi 1804876928 1155 AMYDYVANNEDELNFSKGQLINVLNKDDPDWWQ-GEINGVTGLFPSNYVK 1203
Cdd:cd11849      4 ALYDFKSAEPNTLSFSEGETFLLLERSNAHWWLvTNHSGETGYVPANYVK 53

Src Homology 3 domain of C-terminal Src kinase; CSK is a cytoplasmic (or nonreceptor) tyr kinase containing the Src homology domains, SH3 and SH2, N-terminal to the catalytic tyr kinase domain. They negatively regulate the activity of Src kinases that are anchored to the plasma membrane. To inhibit Src kinases, CSK is translocated to the membrane via binding to specific transmembrane proteins, G-proteins, or adaptor proteins near the membrane. CSK catalyzes the tyr phosphorylation of the regulatory C-terminal tail of Src kinases, resulting in their inactivation. It is expressed in a wide variety of tissues and plays a role, as a regulator of Src, in cell proliferation, survival, and differentiation, and consequently, in cancer development and progression. In addition, CSK also shows Src-independent functions. It is a critical component in G-protein signaling, and plays a role in cytoskeletal reorganization and cell migration. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212703 [Multi-domain] Cd Length: 57 Bit Score: 40.75 E-value: 1.92e-04

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....*.
gi 1804876928 1004 GDEYIALYSYSSVEPGDLTFIEGEEILVTQ--KDGEWWTGSIGD-RTGIFPSNYVK 1056
Cdd:cd11769      1 GTECIAKYNFNGASEEDLPFKKGDILTIVAvtKDPNWYKAKNKDgREGMIPANYVQ 56

Predicted nucleic acid-binding protein DR0291, contains C4-type Zn-ribbon domain [General function prediction only];

Pssm-ID: 441187 [Multi-domain] Cd Length: 236 Bit Score: 44.92 E-value: 1.93e-04

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1804876928  491 ERQRRLewerIRRQELLNQRNREQEEIVRLNSKKKSLHLELEALNGKHQQISGRLQDVRLRKQTQKTEIEVLDKQcdlei 570
Cdd:COG1579      4 EDLRAL----LDLQELDSELDRLEHRLKELPAELAELEDELAALEARLEAAKTELEDLEKEIKRLELEIEEVEAR----- 74

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1804876928  571 meIKQLQQ---------ELQDYQNKLIYLVPEKQLLNERIknmqlgntpdlgIDLLHKKSlEKEELCQRLKEQLDALEKE 641
Cdd:COG1579     75 --IKKYEEqlgnvrnnkEYEALQKEIESLKRRISDLEDEI------------LELMERIE-ELEEELAELEAELAELEAE 139

                          170
                   ....*....|....*.
gi 1804876928  642 TASKLSEMDSFNNQLK 657
Cdd:COG1579    140 LEEKKAELDEELAELE 155

Microtubule associated protein (MAP65/ASE1 family);

Pssm-ID: 427641 [Multi-domain] Cd Length: 477 Bit Score: 46.15 E-value: 1.94e-04

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1804876928  513 EQEEIVRLNSKKKSLH----LELEALNGKHQQISGRLQDVRlrkqtqkTEIEVLDKQCDLEIMEIKQLQQElqdyQNKLI 588
Cdd:pfam03999   18 EDKRLQILSRLKDHIKefytDALSEENDKEQRILQSIADLR-------AEAAILCLYMRNRLLHEERDPFE----PKKGM 86

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1804876928  589 YLVPEKQLLNERIKNMQLGNTPDLgidLLHKKSLEK-EELCQRLKEQLDALEKETASKLSEMDSFNNQLkcGNMDDSVLQ 667
Cdd:pfam03999   87 SLLQKEKKLDTQLEHLRKEKAPRL---AEIKELLEQlQQLCEELGEEPLPLLIDPLPSLEELESFRKHL--ENLRNEKER 161

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1804876928  668 CLLSLLSCLNNLFLLLKELR-------------ESYNTQQLALEQLHKIKRdKLKEIERKRSELIQKKKLEDEAIRkakq 734
Cdd:pfam03999  162 RLEEVNELKKQIKLLMEELDlvpgtdfeedllcESEDNFCLSRENIDKLRK-LIKQLEEQKAEREEKIDDLREKIL---- 236

                          250       260       270       280
                   ....*....|....*....|....*....|....*....|....
gi 1804876928  735 gkeNLWrESLRKEEEEKQKRLQE-----EKTQEKVQEEERKVEE 773
Cdd:pfam03999  237 ---ELW-NRLQVPQEEQESFVREnnslsQDTIDALREELQRLEE 276

C-terminal (or second) Src Homology 3 domain of the p67phox subunit of NADPH oxidase; p67phox, also called Neutrophil cytosol factor 2 (NCF-2), is a cytosolic subunit of the phagocytic NADPH oxidase complex (also called Nox2 or gp91phox) which plays a crucial role in the cellular response to bacterial infection. NADPH oxidase catalyzes the transfer of electrons from NADPH to oxygen during phagocytosis forming superoxide and reactive oxygen species. p67phox plays a regulatory role and contains N-terminal TPR, first SH3 (or N-terminal or central SH3), PB1, and C-terminal SH3 domains. It binds, via its C-terminal SH3 domain, to a proline-rich region of p47phox and upon activation, this complex assembles with flavocytochrome b558, the Nox2-p22phox heterodimer. Concurrently, RacGTP translocates to the membrane and interacts with the TPR domain of p67phox, which leads to the activation of NADPH oxidase. The PB1 domain of p67phox binds to its partner PB1 domain in p40phox, and this facilitates the assembly of p47phox-p67phox at the membrane. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212979 [Multi-domain] Cd Length: 53 Bit Score: 40.94 E-value: 1.96e-04

                           10        20        30        40
                   ....*....|....*....|....*....|....*....|....*....
gi 1804876928  926 ALCSWTAKKDNHLNFSKHDIITVLEQ-QENWWFGEVHGGRGWFPKSYVK 973
Cdd:cd12046      4 ALFSYEASQPEDLEFQKGDVILVLSKvNEDWLEGQCKGKIGIFPSAFVE 52

Second C-terminal Src homology 3 domain of Dynamin Binding Protein, also called Tuba, and similar domains; DNMBP or Tuba is a cdc42-specific guanine nucleotide exchange factor (GEF) that contains four N-terminal SH3 domains, a central RhoGEF [or Dbl homology (DH)] domain followed by a Bin/Amphiphysin/Rvs (BAR) domain, and two C-terminal SH3 domains. It provides a functional link between dynamin, Rho GTPase signaling, and actin dynamics. It plays an important role in regulating cell junction configuration. The C-terminal SH3 domains of DNMBP bind to N-WASP and Ena/VASP proteins, which are key regulatory proteins of the actin cytoskeleton. Also included in this subfamily is the second C-terminal SH3 domain of Rho guanine nucleotide exchange factor 37 (ARHGEF37), whose function is still unknown. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212734 [Multi-domain] Cd Length: 57 Bit Score: 40.82 E-value: 1.96e-04

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|.
gi 1804876928  926 ALCSWTAKKDNHLNFSKHDIITVLEQQE-----NWWFGEVHGGRGWFPKSY 971
Cdd:cd11800      4 ALYTFEARSPGELSVTEGQVVTVLEKHDlkgnpEWWLVEDRGKQGYVPSNY 54

Uncharacterized protein, contains DUF3084 domain [Function unknown];

Pssm-ID: 443500 [Multi-domain] Cd Length: 370 Bit Score: 45.66 E-value: 1.96e-04

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1804876928  401 DKRKANYERGNVELEKRRQ------ALMEQQQREAERKAQKEKEEWERKQRELQEQEWKKQLELEKRLEKQRELErqree 474
Cdd:COG4372      2 DRLGEKVGKARLSLFGLRPktgiliAALSEQLRKALFELDKLQEELEQLREELEQAREELEQLEEELEQARSELE----- 76

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1804876928  475 errkeierreAAKQEL-ERQRRLewerirrQELLNQRNREQEEIVRLNSKKKSLHLELEALNGKHQQISGRLQDVrlrkq 553
Cdd:COG4372     77 ----------QLEEELeELNEQL-------QAAQAELAQAQEELESLQEEAEELQEELEELQKERQDLEQQRKQL----- 134

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1804876928  554 tqKTEIEVLDKQCDLEIMEIKQLQQELQDYQNKLIYLVPEKQLLNEriknmqlgntpdlgidllhkkslekeelcQRLKE 633
Cdd:COG4372    135 --EAQIAELQSEIAEREEELKELEEQLESLQEELAALEQELQALSE-----------------------------AEAEQ 183

                          250       260       270       280       290       300       310       320
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1804876928  634 QLDALEKEtASKLSEMDSFNNQLKCGNMDDSVLQCLLSLLSCLNNLFLLLKELRESYNTQQLALEQLHKIKRDKLKEIER 713
Cdd:COG4372    184 ALDELLKE-ANRNAEKEEELAEAEKLIESLPRELAEELLEAKDSLEAKLGLALSALLDALELEEDKEELLEEVILKEIEE 262

                          330       340       350       360       370       380       390       400
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1804876928  714 KRSELIQKKKLEDEAIRKAKQGKENLWRESLRKEEEEKQKRLQEEKTQEKVQEEERKVEEKQcepASALVNYKALYRFEA 793
Cdd:COG4372    263 LELAILVEKDTEEEELEIAALELEALEEAALELKLLALLLNLAALSLIGALEDALLAALLEL---AKKLELALAILLAEL 339

                          410       420
                   ....*....|....*....|...
gi 1804876928  794 RSHDEMSFNSGDIIQVDEKTIGE 816
Cdd:COG4372    340 ADLLQLLLVGLLDNDVLELLSKG 362

Src Homology 3 domain of alpha-Pak Interactive eXchange factor; Alpha-PIX, also called Rho guanine nucleotide exchange factor 6 (ARHGEF6) or Cool (Cloned out of Library)-2, activates small GTPases by exchanging bound GDP for free GTP. It acts as a GEF for both Cdc42 and Rac 1, and is localized in dendritic spines where it regulates spine morphogenesis. It controls dendritic length and spine density in the hippocampus. Mutations in the ARHGEF6 gene cause X-linked intellectual disability in humans. PIX proteins contain an N-terminal SH3 domain followed by RhoGEF (also called Dbl-homologous or DH) and Pleckstrin Homology (PH) domains, and a C-terminal leucine-zipper domain for dimerization. The SH3 domain of PIX binds to an atypical PxxxPR motif in p21-activated kinases (PAKs) with high affinity. The binding of PAKs to PIX facilitate the localization of PAKs to focal complexes and also localizes PAKs to PIX targets Cdc43 and Rac, leading to the activation of PAKs. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212993 Cd Length: 58 Bit Score: 40.76 E-value: 1.98e-04

                           10        20        30        40
                   ....*....|....*....|....*....|....*....|....
gi 1804876928 1091 EQLSLAPGQLILILKKNSSGWWQGELQARgkkrqKGWFPASHVK 1134
Cdd:cd12060     16 DELSVCKGDIIYVTRVEEGGWWEGTLNGK-----TGWFPSNYVR 54

Coiled-coil domain-containing protein 66; This protein family, named Coiled-coil domain-containing protein 66 (CCDC) refers to a protein domain found in eukaryotes, and is approximately 160 amino acids in length. CCDC66 protein is detected mainly in the inner segments of photoreceptors in many vertebrates including mice and humans. It has been found in dogs, that a mutation in the CCDC66 gene causes generalized progressive retinal atrophy (gPRA). This shows that the protein encoded for by this gene is vital for healthy vision and guards against photoreceptor cell degeneration. The structure of CCDC66 proteins includes a heptad repeat pattern which contains at least one coiled-coil domain. There are at least two or more alpha-helices which form a cable-like structure.

Pssm-ID: 434558 [Multi-domain] Cd Length: 154 Bit Score: 43.63 E-value: 1.98e-04

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1804876928  384 QKIQEEEPQKKLpvtfEDKRKANyERGNVELEKRRQALMEQQQREAERKAQKEKEE-WERKQRELQE-----QEWKKQLE 457
Cdd:pfam15236   63 KQLEEKERQKKL----EEERRRQ-EEQEEEERLRREREEEQKQFEEERRKQKEKEEaMTRKTQALLQamqkaQELAQRLK 137


                   ....
gi 1804876928  458 LEKR 461
Cdd:pfam15236  138 QEQR 141

Src homology 3 domain of CAS (Crk-Associated Substrate) scaffolding protein family member, Neural precursor cell Expressed, Developmentally Down-regulated 9; NEDD9 is also called human enhancer of filamentation 1 (HEF1) or CAS-L (Crk-associated substrate in lymphocyte). It was first described as a gene predominantly expressed in early embryonic brain, and was also isolated from a screen of human proteins that regulate filamentous budding in yeast, and as a tyrosine phosphorylated protein in lymphocytes. It promotes metastasis in different solid tumors. NEDD9 localizes in focal adhesions and associates with FAK and Abl kinase. It also interacts with SMAD3 and the proteasomal machinery which allows its rapid turnover; these interactions are not shared by other CAS proteins. CAS proteins function as molecular scaffolds to regulate protein complexes that are involved in many cellular processes. They share a common domain structure that includes an N-terminal SH3 domain, an unstructured substrate domain that contains many YxxP motifs, a serine-rich four-helix bundle, and a FAT-like C-terminal domain. The SH3 domain of CAS proteins binds to diverse partners including FAK, FRNK, Pyk2, PTP-PEST, DOCK180, among others. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212935 Cd Length: 57 Bit Score: 40.74 E-value: 2.01e-04

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|...
gi 1804876928 1155 AMYDYVANNEDELNFSKGQLINVLNKDD---PDWWQGEINGVTGLFPSNYVKM 1204
Cdd:cd12002      4 ALYDNVPECAEELAFRKGDILTVIEQNTgglEGWWLCSLHGRQGIAPGNRLKL 56

Src homology 3 domain of Yes Protein Tyrosine Kinase; Yes (or c-Yes) is a member of the Src subfamily of proteins, which are cytoplasmic (or non-receptor) PTKs. c-Yes kinase is the cellular homolog of the oncogenic protein (v-Yes) encoded by the Yamaguchi 73 and Esh sarcoma viruses. It displays functional overlap with other Src subfamily members, particularly Src. It also shows some unique functions such as binding to occludins, transmembrane proteins that regulate extracellular interactions in tight junctions. Yes also associates with a number of proteins in different cell types that Src does not interact with, like JAK2 and gp130 in pre-adipocytes, and Pyk2 in treated pulmonary vein endothelial cells. Although the biological function of Yes remains unclear, it appears to have a role in regulating cell-cell interactions and vesicle trafficking in polarized cells. Src kinases contain an N-terminal SH4 domain with a myristoylation site, followed by SH3 and SH2 domains, a tyr kinase domain, and a regulatory C-terminal region containing a conserved tyr. They are activated by autophosphorylation at the tyr kinase domain, but are negatively regulated by phosphorylation at the C-terminal tyr by Csk (C-terminal Src Kinase). The SH3 domain of Src kinases contributes to substrate recruitment by binding adaptor proteins/substrates, and regulation of kinase activity through an intramolecular interaction. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212940 [Multi-domain] Cd Length: 58 Bit Score: 40.79 E-value: 2.01e-04

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|...
gi 1804876928  785 YKALYRFEARSHDEMSFNSGDIIQVDEKTIGEpGWLYGSFQ-GNFGWFPCNYV 836
Cdd:cd12007      3 FVALYDYEARTTEDLSFKKGERFQIINNTEGD-WWEARSIAtGKNGYIPSNYV 54

Second Src Homology 3 domain of the fungal endocytic adaptor protein Sla1p; Sla1p facilitates endocytosis by playing a role as an adaptor protein in coupling components of the actin cytoskeleton to the endocytic machinery. It interacts with Abp1p, Las17p and Pan1p, which are activator proteins of actin-related protein 2/3 (Arp2/3). Sla1p contains multiple domains including three SH3 domains, a SAM (sterile alpha motif) domain, and a Sla1 homology domain 1 (SHD1), which binds to the NPFXD motif that is found in many integral membrane proteins such as the Golgi-localized Arf-binding protein Lsb5p and the P4-ATPases, Drs2p and Dnf1p. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212708 [Multi-domain] Cd Length: 52 Bit Score: 40.53 E-value: 2.03e-04

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                   ....*....|....*....|....*....|....*....|....*....|..
gi 1804876928  786 KALYRFEARSHDEMSFNSGDIIQVDEKTigEPGW-LYGSFQGNFGWFPCNYV 836
Cdd:cd11774      3 KALYDYDKQTEEELSFNEGDTLDVYDDS--DSDWiLVGFNGTQFGFVPANYI 52

Src homology 3 domain of Protein kinase C and Casein kinase Substrate in Neurons 1 (PACSIN1) and PACSIN 2; PACSIN 1 or Syndapin I (Synaptic dynamin-associated protein I) is expressed specifically in the brain and is localized in neurites and synaptic boutons. It binds the brain-specific proteins dynamin I, synaptojanin, synapsin I, and neural Wiskott-Aldrich syndrome protein (nWASP), and functions as a link between the cytoskeletal machinery and synaptic vesicle endocytosis. PACSIN 1 interacts with huntingtin and may be implicated in the neuropathology of Huntington's disease. PACSIN 2 or Syndapin II is expressed ubiquitously and is involved in the regulation of tubulin polymerization. It associates with Golgi membranes and forms a complex with dynamin II which is crucial in promoting vesicle formation from the trans-Golgi network. PACSINs act as regulators of cytoskeletal and membrane dynamics. Vetebrates harbor three isoforms with distinct expression patterns and specific functions. PACSINs contain an N-terminal F-BAR domain and a C-terminal SH3 domain. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212931 [Multi-domain] Cd Length: 56 Bit Score: 40.70 E-value: 2.06e-04

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                   ....*....|....*....|....*....|....*....|....*....|..
gi 1804876928 1009 ALYSYSSVEPGDLTFIEGEEILVTQKDGE--WWTGSI-GDRTGIFPSNYVKP 1057
Cdd:cd11998      5 ALYDYDGQEQDELSFKAGDELTKLEDEDEqgWCKGRLdSGQVGLYPANYVEP 56

Src homology 3 domain of CAS (Crk-Associated Substrate) scaffolding protein family member, Embryonal Fyn-associated Substrate; EFS is also called HEFS, CASS3 (Cas scaffolding protein family member 3) or SIN (Src-interacting protein). It was identified based on interactions with the Src kinases, Fyn and Yes. It plays a role in thymocyte development and acts as a negative regulator of T cell proliferation. CAS proteins function as molecular scaffolds to regulate protein complexes that are involved in many cellular processes. They share a common domain structure that includes an N-terminal SH3 domain, an unstructured substrate domain that contains many YxxP motifs, a serine-rich four-helix bundle, and a FAT-like C-terminal domain. The SH3 domain of CAS proteins binds to diverse partners including FAK, FRNK, Pyk2, PTP-PEST, DOCK180, among others. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212936 Cd Length: 62 Bit Score: 41.03 E-value: 2.09e-04

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....*...
gi 1804876928  786 KALYRFEARSHDEMSFNSGDIIQVDEKTIGE-PGWLYGSFQGNFGWFPCNYVEKMPSG 842
Cdd:cd12003      4 KALYDNAAESPEELSFRRGDVLMVLKREHGSlPGWWLCSLHGQQGIAPANRLRLLPTA 61

Second Src Homology 3 domain of Nck2 adaptor protein; Nck2 (also called Nckbeta or Growth factor receptor-bound protein 4, Grb4) plays a crucial role in connecting signaling pathways of tyrosine kinase receptors and important effectors in actin dynamics and cytoskeletal remodeling. It binds neuronal signaling proteins such as ephrinB and Disabled-1 (Dab-1) exclusively. Nck adaptor proteins regulate actin cytoskeleton dynamics by linking proline-rich effector molecules to protein tyrosine kinases and phosphorylated signaling intermediates. They contain three SH3 domains and a C-terminal SH2 domain. They function downstream of the PDGFbeta receptor and are involved in Rho GTPase signaling and actin dynamics. Vertebrates contain two Nck adaptor proteins: Nck1 (also called Nckalpha) and Nck2, which show partly overlapping functions but also bind distinct targets. The second SH3 domain of Nck appears to prefer ligands containing the APxxPxR motif. SH3 domains are protein interaction domains that usually bind to proline-rich ligands with moderate affinity and selectivity, preferentially a PxxP motif. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212835 [Multi-domain] Cd Length: 55 Bit Score: 40.76 E-value: 2.14e-04

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                   ....*....|....*....|....*....|....*....|....*..
gi 1804876928 1011 YSYSSVEPGDLTFIEGEEILVTQK--DGeWWTGSIGDRTGIFPSNYV 1055
Cdd:cd11902      7 FAYVAEREDELSLVKGSRVTVMEKcsDG-WWRGSYNGQIGWFPSNYV 52

Third Src Homology 3 domain (SH3C) of CD2-associated protein and similar proteins; This subfamily is composed of the third SH3 domain (SH3C) of CD2AP, CIN85 (Cbl-interacting protein of 85 kDa), and similar domains. CD2AP and CIN85 are adaptor proteins that bind to protein partners and assemble complexes that have been implicated in T cell activation, kidney function, and apoptosis of neuronal cells. They also associate with endocytic proteins, actin cytoskeleton components, and other adaptor proteins involved in receptor tyrosine kinase (RTK) signaling. CD2AP and the main isoform of CIN85 contain three SH3 domains, a proline-rich region, and a C-terminal coiled-coil domain. All of these domains enable CD2AP and CIN85 to bind various protein partners and assemble complexes that have been implicated in many different functions. SH3C of both proteins have been shown to bind to ubiquitin. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212808 [Multi-domain] Cd Length: 55 Bit Score: 40.80 E-value: 2.25e-04

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                   ....*....|....*....|....*....|....*....|....*....|....*....
gi 1804876928 1079 AQVTSAYVASGSEQLSLAPGQLILILKKNS--SGWWQGELQARgkkrqKGWFPASHVKL 1135
Cdd:cd11875      2 ARVLFDYEAENEDELTLREGDIVTILSKDCedKGWWKGELNGK-----RGVFPDNFVEP 55

Src homology 3 domain of Slit-Robo GTPase Activating Protein 4; srGAP4, also called ARHGAP4, is highly expressed in hematopoietic cells and may play a role in lymphocyte differentiation. It is able to stimulate the GTPase activity of Rac1, Cdc42, and RhoA. In the nervous system, srGAP4 has been detected in differentiating neurites and may be involved in axon and dendritic growth. srGAPs are Rho GAPs that interact with Robo1, the transmembrane receptor of Slit proteins. Slit proteins are secreted proteins that control axon guidance and the migration of neurons and leukocytes. srGAPs contain an N-terminal F-BAR domain, a Rho GAP domain, and a C-terminal SH3 domain. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212889 [Multi-domain] Cd Length: 55 Bit Score: 40.59 E-value: 2.35e-04

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                   ....*....|....*....|....*....|....*....|....*....|....
gi 1804876928  922 LKAQALCSWTAKKDNHLNFSKHDIITVLEQ-QENWWFGEVHGGRGWFPKSYVKI 974
Cdd:cd11956      2 VEAVACFDYTGRTAQELSFKRGDVLLLHSKaSSDWWRGEHNGMRGLIPHKYISV 55

Src homology 3 domain of Type I fungal Myosins; Type I myosins (myosin-I) are actin-dependent motors in endocytic actin structures and actin patches. They play roles in membrane traffic in endocytic and secretory pathways, cell motility, and mechanosensing. Saccharomyces cerevisiae has two myosins-I, Myo3 and Myo5, which are involved in endocytosis and the polarization of the actin cytoskeleton. Myosin-I contains an N-terminal actin-activated ATPase, a phospholipid-binding TH1 (tail homology 1) domain, and a C-terminal extension which includes an F-actin-binding TH2 domain, an SH3 domain, and an acidic peptide that participates in activating the Arp2/3complex. The SH3 domain of myosin-I is required for myosin-I-induced actin polymerization. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212792 [Multi-domain] Cd Length: 55 Bit Score: 40.45 E-value: 2.36e-04

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                   ....*....|....*....|....*....|....*....|....*....|.
gi 1804876928 1085 YVASGSEQLSLAPGQLILILKKNSSGWWqgeLQARGKKRQKGWFPASHVKL 1135
Cdd:cd11858      8 FAGSVANELSLKKDDIVYIVQKEDNGWW---LAKKLDESKEGWVPAAYLEE 55

C-terminal (or second) Src homology 3 domain of VAV3 protein; VAV3 is ubiquitously expressed and functions as a phosphorylation-dependent guanine nucleotide exchange factor (GEF) for RhoA, RhoG, and Rac1. It has been implicated to function in the hematopoietic, bone, cerebellar, and cardiovascular systems. VAV3 is essential in axon guidance in neurons that control blood pressure and respiration. It is overexpressed in prostate cancer cells and it plays a role in regulating androgen receptor transcriptional activity. VAV proteins contain several domains that enable their function: N-terminal calponin homology (CH), acidic, RhoGEF (also called Dbl-homologous or DH), Pleckstrin Homology (PH), C1 (zinc finger), SH2, and two SH3 domains. The SH3 domain of VAV is involved in the localization of proteins to specific sites within the cell, by interacting with proline-rich sequences within target proteins. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212911 [Multi-domain] Cd Length: 56 Bit Score: 40.78 E-value: 2.39e-04

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                   ....*....|....*....|....*....|....*....|....*....|....*...
gi 1804876928 1078 IAQVTSAYVASGSEQLSLAPGQLILI-LKKNSSGWWQGELQARgkkrqKGWFPASHVK 1134
Cdd:cd11978      2 IAIARYDFCARDMRELSLLKGDVVKIyTKMSTNGWWRGEVNGR-----VGWFPSTYVE 54

N-terminal Src homology 3 domain of Growth factor receptor-bound protein 2 (GRB2) and related proteins; This family includes the adaptor protein GRB2 and related proteins including Drosophila melanogaster Downstream of receptor kinase (DRK), Caenorhabditis elegans Sex muscle abnormal protein 5 (Sem-5), GRB2-related adaptor protein (GRAP), GRAP2, and similar proteins. Family members contain an N-terminal SH3 domain, a central SH2 domain, and a C-terminal SH3 domain. GRB2/Sem-5/DRK is a critical signaling molecule that regulates the Ras pathway by linking tyrosine kinases to the Ras guanine nucleotide releasing protein Sos (son of sevenless), which converts Ras to the active GTP-bound state. GRAP2 plays an important role in T cell receptor (TCR) signaling by promoting the formation of the SLP-76:LAT complex, which couples the TCR to the Ras pathway. GRAP acts as a negative regulator of T cell receptor (TCR)-induced lymphocyte proliferation by downregulating the signaling to the Ras/ERK pathway. The N-terminal SH3 domain of GRB2 binds to Sos and Sos-derived proline-rich peptides. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212738 [Multi-domain] Cd Length: 52 Bit Score: 40.42 E-value: 2.43e-04

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gi 1804876928 1006 EYIALYSYSSVEPGDLTFIEGE--EILVTQKDGEWWTGSIGDRTGIFPSNYV 1055
Cdd:cd11804      1 EAVAKHDFKATAEDELSFKKGSilKVLNMEDDPNWYKAELDGKEGLIPKNYI 52

Src Homology 3 domain of Mixed Lineage Kinases; MLKs are Serine/Threonine Kinases (STKs), catalyzing the transfer of the gamma-phosphoryl group from ATP to S/T residues on protein substrates. MLKs act as mitogen-activated protein kinase kinase kinases (MAP3Ks, MKKKs, MAPKKKs), which phosphorylate and activate MAPK kinases (MAPKKs or MKKs or MAP2Ks), which in turn phosphorylate and activate MAPKs during signaling cascades that are important in mediating cellular responses to extracellular signals. MLKs play roles in immunity and inflammation, as well as in cell death, proliferation, and cell cycle regulation. Mammals have four MLKs (MLK1-4), mostly conserved in vertebrates, which contain an SH3 domain, a catalytic kinase domain, a leucine zipper, a proline-rich region, and a CRIB domain that mediates binding to GTP-bound Cdc42 and Rac. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212809 [Multi-domain] Cd Length: 58 Bit Score: 40.57 E-value: 2.50e-04

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                   ....*....|....*....|....*....|....*....|....*....|....
gi 1804876928 1085 YVASGSEQLSLAPGQLILILKKNSS-----GWWQGELQARgkkrqKGWFPASHV 1133
Cdd:cd11876      8 YDARGEDELTLRRGQPVEVLSKDAAvsgdeGWWTGKIGDK-----VGIFPSNYV 56

Src Homology 3 domain of Melanoma Inhibitory Activity protein and similar proteins; MIA is a single domain protein that adopts a SH3 domain-like fold; it contains an additional antiparallel beta sheet and two disulfide bonds compared to classical SH3 domains. MIA is secreted from malignant melanoma cells and it plays an important role in melanoma development and invasion. MIA is expressed by chondrocytes in normal tissues and may be important in the cartilage cell phenotype. Unlike classical SH3 domains, MIA does not bind proline-rich ligands. MIA is a member of the recently identified family that also includes MIA-like (MIAL), MIA2, and MIA3 (also called TANGO); the biological functions of this family are not yet fully understood.

Pssm-ID: 212694 Cd Length: 76 Bit Score: 41.31 E-value: 2.64e-04

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                   ....*....|....*....|....*....|....*....|....*....|....*....|..
gi 1804876928 1148 HPVCQVIAMYDYVANNEDELNFSKGQLINVLNK---DDPDWWQGEINGVTGL---FPSNYVK 1203
Cdd:cd11760      9 NPISRARALEDYHGPDCRFLNFKKGDTIYVYSKlagERQDLWAGSVGGDAGLfgyFPKNLVQ 70

Src Homology 3 domain of SH3 domain and tetratricopeptide repeat-containing (SH3TC) proteins and similar domains; This subfamily is composed of vertebrate SH3TC proteins and hypothetical fungal proteins containing BAR and SH3 domains. Mammals contain two SH3TC proteins, SH3TC1 and SH3TC2. The function of SH3TC1 is unknown. SH3TC2 is localized in Schwann cells in the peripheral nervous system, where it interacts with Rab11 and plays a role in peripheral nerve myelination. Mutations in SH3TC2 are associated with Charcot-Marie-Tooth disease type 4C, a severe hereditary peripheral neuropathy with symptoms that include progressive scoliosis, delayed age of walking, muscular atrophy, distal weakness, and reduced nerve conduction velocity. SH3 domains bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs; they play a role in the regulation of enzymes by intramolecular interactions, changing the subcellular localization of signal pathway components and mediate multiprotein complex assemblies.

Pssm-ID: 212818 Cd Length: 55 Bit Score: 40.38 E-value: 2.76e-04

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gi 1804876928 1009 ALYSYSSVEPGDLTFIEGEEILVT---QKDGEWWTGSIGD--RTGIFPSNYV 1055
Cdd:cd11885      4 AKMDFEGVEPGELSFRQGDSIEIIgdlIPGLQWFVGRSKSsgRVGFVPTNHF 55

Second Src Homology 3 domain (SH3B) of CD2-associated protein; CD2AP, also called CMS (Cas ligand with Multiple SH3 domains) or METS1 (Mesenchyme-to-Epithelium Transition protein with SH3 domains), is a cytosolic adaptor protein that plays a role in regulating the cytoskeleton. It is critical in cell-to-cell union necessary for kidney function. It also stabilizes the contact between a T cell and antigen-presenting cells. It is primarily expressed in podocytes at the cytoplasmic face of the slit diaphragm and serves as a linker anchoring podocin and nephrin to the actin cytoskeleton. CD2AP contains three SH3 domains, a proline-rich region, and a C-terminal coiled-coil domain. All of these domains enable CD2AP to bind various protein partners and assemble complexes that have been implicated in many different functions. This alignment model represents the second SH3 domain (SH3B) of CD2AP. SH3B binds to c-Cbl in a site (TPSSRPLR is the core binding motif) distinct from the c-Cbl/SH3A binding site. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212987 [Multi-domain] Cd Length: 55 Bit Score: 40.34 E-value: 2.78e-04

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gi 1804876928 1010 LYSYSSVEPGDLTFIEGEEILVTQKDGE-WWTGSIGDRTGIFPSNYVK 1056
Cdd:cd12054      6 LFEYVPQNEDELELKVGDIIDINEEVEEgWWSGTLNGKSGLFPSNFVK 53

Second Src Homology 3 domain (SH3B) of CD2-associated protein and similar proteins; This subfamily is composed of the second SH3 domain (SH3B) of CD2AP, CIN85 (Cbl-interacting protein of 85 kDa), and similar domains. CD2AP and CIN85 are adaptor proteins that bind to protein partners and assemble complexes that have been implicated in T cell activation, kidney function, and apoptosis of neuronal cells. They also associate with endocytic proteins, actin cytoskeleton components, and other adaptor proteins involved in receptor tyrosine kinase (RTK) signaling. CD2AP and the main isoform of CIN85 contain three SH3 domains, a proline-rich region, and a C-terminal coiled-coil domain. All of these domains enable CD2AP and CIN85 to bind various protein partners and assemble complexes that have been implicated in many different functions. SH3B of both proteins have been shown to bind to Cbl. In the case of CD2AP, its SH3B binds to Cbl at a site distinct from the c-Cbl/SH3A binding site. The CIN85 SH3B also binds ubiquitin. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212807 [Multi-domain] Cd Length: 53 Bit Score: 40.39 E-value: 2.80e-04

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gi 1804876928 1079 AQVTSAYVASGSEQLSLAPGQLILILKKNSSGWWqgelqaRGKKRQK-GWFPASHVKL 1135
Cdd:cd11874      2 CKVLFSYTPQNEDELELKVGDTIEVLGEVEEGWW------EGKLNGKvGVFPSNFVKE 53

Src Homology 3 domain of Membrane Protein, Palmitoylated 2 (or MAGUK p55 subfamily member 2); MPP2 is a scaffolding protein that interacts with the non-receptor tyrosine kinase c-Src in epithelial cells to negatively regulate its activity and morphological function. It is one of seven vertebrate homologs of the Drosophila Stardust protein, which is required in establishing cell polarity, and it contains two L27 domains followed by the core of three domains characteristic of MAGUK (membrane-associated guanylate kinase) proteins: PDZ, SH3, and guanylate kinase (GuK). In addition, it also contains the Hook (Protein 4.1 Binding) motif in between the SH3 and GuK domains. The GuK domain in MAGUK proteins is enzymatically inactive; instead, the domain mediates protein-protein interactions and associates intramolecularly with the SH3 domain. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212970 Cd Length: 59 Bit Score: 40.71 E-value: 2.82e-04

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gi 1804876928 1164 EDELNFSKGQLINVLNKDDPDWWQGEI--NGVTGLFPS 1199
Cdd:cd12037     20 EAGLKFRAGDLLQIVNQEDPNWWQACHveGGSAGLIPS 57

Second C-terminal Src homology 3 domain of Dynamin Binding Protein, also called Tuba, and similar domains; DNMBP or Tuba is a cdc42-specific guanine nucleotide exchange factor (GEF) that contains four N-terminal SH3 domains, a central RhoGEF [or Dbl homology (DH)] domain followed by a Bin/Amphiphysin/Rvs (BAR) domain, and two C-terminal SH3 domains. It provides a functional link between dynamin, Rho GTPase signaling, and actin dynamics. It plays an important role in regulating cell junction configuration. The C-terminal SH3 domains of DNMBP bind to N-WASP and Ena/VASP proteins, which are key regulatory proteins of the actin cytoskeleton. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 213017 [Multi-domain] Cd Length: 57 Bit Score: 40.56 E-value: 2.88e-04

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                   ....*....|....*....|....*....|....*....|....*....|...
gi 1804876928  926 ALCSWTAKKDNHLNFSKHDIITVLEQQE-----NWWFGEVHGGRGWFPKSYVK 973
Cdd:cd12141      4 AVYTFKARSPNELSVSANQRVRILEFSDltgnkEWWLAEANGQKGYVPSNYIR 56

Src homology 3 domain of Fyn and Yrk Protein Tyrosine Kinases; Fyn and Yrk (Yes-related kinase) are members of the Src subfamily of proteins, which are cytoplasmic (or non-receptor) PTKs. Fyn, together with Lck, plays a critical role in T-cell signal transduction by phosphorylating ITAM (immunoreceptor tyr activation motif) sequences on T-cell receptors, ultimately leading to the proliferation and differentiation of T-cells. In addition, Fyn is involved in the myelination of neurons, and is implicated in Alzheimer's and Parkinson's diseases. Yrk has been detected only in chickens. It is primarily found in neuronal and epithelial cells and in macrophages. It may play a role in inflammation and in response to injury. Src kinases contain an N-terminal SH4 domain with a myristoylation site, followed by SH3 and SH2 domains, a tyr kinase domain, and a regulatory C-terminal region containing a conserved tyr. They are activated by autophosphorylation at the tyr kinase domain, but are negatively regulated by phosphorylation at the C-terminal tyr by Csk (C-terminal Src Kinase). The SH3 domain of Src kinases contributes to substrate recruitment by binding adaptor proteins/substrates, and regulation of kinase activity through an intramolecular interaction. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212939 [Multi-domain] Cd Length: 56 Bit Score: 40.42 E-value: 2.91e-04

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gi 1804876928  785 YKALYRFEARSHDEMSFNSGDIIQVDEKTIGEpGWLYGSF-QGNFGWFPCNYV 836
Cdd:cd12006      3 FVALYDYEARTEDDLSFHKGEKFQILNSSEGD-WWEARSLtTGETGYIPSNYV 54

First Src homology 3 domain of Tyrosine kinase substrate (Tks) proteins; Tks proteins are Src substrates and scaffolding proteins that play important roles in the formation of podosomes and invadopodia, the dynamic actin-rich structures that are related to cell migration and cancer cell invasion. Vertebrates contain two Tks proteins, Tks4 (Tyr kinase substrate with four SH3 domains) and Tks5 (Tyr kinase substrate with five SH3 domains), which display partially overlapping but non-redundant functions. Both associate with the ADAMs family of transmembrane metalloproteases, which function as sheddases and mediators of cell and matrix interactions. Tks5 interacts with N-WASP and Nck, while Tks4 is essential for the localization of MT1-MMP (membrane-type 1 matrix metalloproteinase) to invadopodia. Tks proteins contain an N-terminal Phox homology (PX) domain and four or five SH3 domains. This model characterizes the first SH3 domain of Tks proteins. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212948 Cd Length: 53 Bit Score: 40.10 E-value: 2.94e-04

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gi 1804876928  918 VVENLKAQalcswtakKDNHLNFSKHDIITVLEQQEN-WWFGEVHGGRGWFPKSY 971
Cdd:cd12015      4 VVADYKKQ--------QPNEISLRAGDVVDVIEKNENgWWFVSLEDEQGWVPATY 50

Third Src homology 3 domain (or SH3C) of Intersectin-2; Intersectin-2 (ITSN2) is an adaptor protein that functions in exo- and endocytosis, actin cytoskeletal reorganization, and signal transduction. It plays a role in clathrin-coated pit (CCP) formation. It binds to many proteins through its multidomain structure and facilitate the assembly of multimeric complexes. ITSN2 also functions as a specific GEF for Cdc42 activation in epithelial morphogenesis, and is required in mitotic spindle orientation. It exists in alternatively spliced short and long isoforms. The short isoform contains two Eps15 homology domains (EH1 and EH2), a coiled-coil region and five SH3 domains (SH3A-E), while the long isoform, in addition, contains RhoGEF (also called Dbl-homologous or DH), Pleckstrin homology (PH) and C2 domains. The third SH3 domain (SH3C) of ITSN2 has been shown to bind the K15 protein of Kaposi's sarcoma-associated herpesvirus. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212925 Cd Length: 52 Bit Score: 40.38 E-value: 3.01e-04

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                   ....*....|....*....|....*....|....*....|....*....|..
gi 1804876928  785 YKALYRFEARSHDEMSFNSGDIIQVDEKTiGEpgWLYGSFQGNFGWFPCNYV 836
Cdd:cd11992      2 YIALYPYSSSEPGDLTFNEGEEILVTQKD-GE--WWTGSIEDRTGIFPSNYV 50

Src Homology 3 domain of Membrane Protein, Palmitoylated 3 (or MAGUK p55 subfamily member 3); MPP3 is a scaffolding protein that colocalizes with MPP5 and CRB1 at the subdpical region adjacent to adherens junctions and may function in photoreceptor polarity. It interacts with some nectins and regulates their trafficking and processing. Nectins are cell-cell adhesion proteins involved in the establishment apical-basal polarity at cell adhesion sites. It is one of seven vertebrate homologs of the Drosophila Stardust protein, which is required in establishing cell polarity, and it contains two L27 domains followed by the core of three domains characteristic of MAGUK (membrane-associated guanylate kinase) proteins: PDZ, SH3, and guanylate kinase (GuK). The GuK domain in MAGUK proteins is enzymatically inactive; instead, the domain mediates protein-protein interactions and associates intramolecularly with the SH3 domain. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212972 Cd Length: 62 Bit Score: 40.71 E-value: 3.04e-04

                           10        20        30        40        50        60
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 1804876928 1138 PSSERTTPafhpvCQviamydyvannEDELNFSKGQLINVLNKDDPDWWQ----GEINGVTGLFPS 1199
Cdd:cd12039     10 PYEDRAIP-----CQ-----------EAGLPFKRRDILEVVSQDDPTWWQakrvGDTNLRAGLIPS 59

Src Homology 3 domain of metazoan osteoclast stimulating factor 1; OSTF1, also named OSF or SH3P2, is a signaling protein containing SH3 and ankyrin-repeat domains. It acts through a Src-related pathway to enhance the formation of osteoclasts and bone resorption. It also acts as a negative regulator of cell motility. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212706 [Multi-domain] Cd Length: 53 Bit Score: 40.36 E-value: 3.10e-04

                           10        20        30        40
                   ....*....|....*....|....*....|....*....|....*...
gi 1804876928  926 ALCSWTAKKDNHLNFSKHDIITVLEQQE-NWWFGEVHGGRGWFPKSYV 972
Cdd:cd11772      4 ALYDYEAQHPDELSFEEGDLLYISDKSDpNWWKATCGGKTGLIPSNYV 51

Second Src Homology 3 domain of SH3 domain containing ring finger proteins; This model represents the second SH3 domain of SH3RF1 (or POSH), SH3RF2 (or POSHER), SH3RF3 (POSH2), and similar domains. Members of this family are scaffold proteins that function as E3 ubiquitin-protein ligases. They all contain an N-terminal RING finger domain and multiple SH3 domains; SH3RF1 and SH3RF3 have four SH3 domains while SH3RF2 has three. SH3RF1 plays a role in calcium homeostasis through the control of the ubiquitin domain protein Herp. It may also have a role in regulating death receptor mediated and JNK mediated apoptosis. SH3RF3 interacts with p21-activated kinase 2 (PAK2) and GTP-loaded Rac1. It may play a role in regulating JNK mediated apoptosis in certain conditions. SH3RF2 acts as an anti-apoptotic regulator of the JNK pathway by binding to and promoting the degradation of SH3RF1. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212721 [Multi-domain] Cd Length: 53 Bit Score: 40.01 E-value: 3.15e-04

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....
gi 1804876928 1008 IALYSYssvEPGD------LTFIEGEEILVTQK-DGEWWTGSIGDRTGIFPSNY 1054
Cdd:cd11787      3 KALYDF---EMKDedekdcLTFKKGDVITVIRRvDENWAEGRLGDKIGIFPISF 53

First C-terminal Src homology 3 domain of SH3 and cysteine-rich domain-containing (Stac) proteins; Stac proteins are putative adaptor proteins that contain a cysteine-rich C1 domain and one or two SH3 domains at the C-terminus. There are three mammalian members (Stac1, Stac2, and Stac3) of this family. Stac1 and Stac3 contain two SH3 domains while Stac2 contains a single SH3 domain at the C-terminus. This model represents the first C-terminal SH3 domain of Stac1 and Stac3, and the single C-terminal SH3 domain of Stac2. Stac1 and Stac2 have been found to be expressed differently in mature dorsal root ganglia (DRG) neurons. Stac1 is mainly expressed in peptidergic neurons while Stac2 is found in a subset of nonpeptidergic and all trkB+ neurons. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212767 [Multi-domain] Cd Length: 53 Bit Score: 40.18 E-value: 3.28e-04

                           10        20        30        40
                   ....*....|....*....|....*....|....*....|....*...
gi 1804876928  926 ALCSWTAKKDNHLNFSKHDIITVLE-QQENWWFGEVHGGRGWFPKSYV 972
Cdd:cd11833      4 ALYKFKPQENEDLEMRPGDKITLLDdSNEDWWKGKIEDRVGFFPANFV 51

First Src Homology 3 domain of Sorbin and SH3 domain containing 2 (Sorbs2), also called Arg-binding protein 2 (ArgBP2); Sorbs2 or ArgBP2 is an adaptor protein containing one sorbin homology (SoHo) and three SH3 domains. It regulates actin-dependent processes including cell adhesion, morphology, and migration. It is expressed in many tissues and is abundant in the heart. Like vinexin, it is found in focal adhesion where it interacts with vinculin and afadin. It also localizes in epithelial cell stress fibers and in cardiac muscle cell Z-discs. Sorbs2 has been implicated to play roles in the signaling of c-Arg, Akt, and Pyk2. Other interaction partners of Sorbs2 include c-Abl, flotillin, spectrin, dynamin 1/2, synaptojanin, PTP-PEST, among others. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212853 [Multi-domain] Cd Length: 55 Bit Score: 40.38 E-value: 3.28e-04

                           10        20        30        40
                   ....*....|....*....|....*....|....*....|....*....
gi 1804876928 1009 ALYSYSSVEPGDLTFIEGEEILVTQK-DGEWWTGSIGDRTGIFPSNYVK 1056
Cdd:cd11920      5 AVYDFKAQTSKELSFKKGDTVYILRKiDQNWYEGEHHGRVGIFPISYVE 53

Third N-terminal Src homology 3 domain of Dynamin Binding Protein, also called Tuba; DNMBP or Tuba is a cdc42-specific guanine nucleotide exchange factor (GEF) that contains four N-terminal SH3 domains, a central RhoGEF [or Dbl homology (DH)] domain followed by a Bin/Amphiphysin/Rvs (BAR) domain, and two C-terminal SH3 domains. It provides a functional link between dynamin and key regulatory proteins of the actin cytoskeleton. It plays an important role in regulating cell junction configuration. The four N-terminal SH3 domains of DNMBP binds the GTPase dynamin, which plays an important role in the fission of endocytic vesicles. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212730 Cd Length: 51 Bit Score: 40.03 E-value: 3.35e-04

                           10        20        30        40
                   ....*....|....*....|....*....|....*....|....*...
gi 1804876928 1009 ALYSYSSVEPGDLTFIEGEEILVTQ-KDGEWWTGSIGDRTGIFPSNYV 1055
Cdd:cd11796      4 VLQDLSAQLDEELDLREGDVVTITGiLDKGWFRGELNGRRGIFPEGFV 51

Src Homology 3 domain of the p40phox subunit of NADPH oxidase; p40phox, also called Neutrophil cytosol factor 4 (NCF-4), is a cytosolic subunit of the phagocytic NADPH oxidase complex (also called Nox2 or gp91phox) which plays a crucial role in the cellular response to bacterial infection. NADPH oxidase catalyzes the transfer of electrons from NADPH to oxygen during phagocytosis forming superoxide and reactive oxygen species. p40phox positively regulates NADPH oxidase in both phosphatidylinositol-3-phosphate (PI3P)-dependent and PI3P-independent manner. It contains an N-terminal PX domain, a central SH3 domain, and a C-terminal PB1 domain that interacts with p67phox. The SH3 domain of p40phox binds to canonical polyproline and noncanonical motifs at the C-terminus of p47phox. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212802 Cd Length: 54 Bit Score: 40.17 E-value: 3.42e-04

                           10        20        30        40
                   ....*....|....*....|....*....|....*....|....*....
gi 1804876928 1009 ALYSYSSVEPGDLTFIEGEEI-LVTQKDGEWWTGSIGDRTGIFPSNYVK 1056
Cdd:cd11869      4 ALFDFTGNSKLELNFKAGDVIfLLSRVNKDWLEGTVRGATGIFPLSFVK 52

Uncharacterized coiled-coil protein, contains DUF342 domain [Function unknown];

Pssm-ID: 440951 [Multi-domain] Cd Length: 297 Bit Score: 44.52 E-value: 3.58e-04

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1804876928  398 TFEDKRKANYERGNvELEKRRQALMEQ---------QQREAERKAQKEKEEWERKQRELQEQEWKKQ-----LELEKRLe 463
Cdd:COG1340     61 ELREKRDELNEKVK-ELKEERDELNEKlnelreeldELRKELAELNKAGGSIDKLRKEIERLEWRQQtevlsPEEEKEL- 138

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1804876928  464 kqrelerqreeerrkeierreaakqeLERQRRLEwERIRRQEllnQRNREQEEIVRLNSKKKSLHLELEALNGKHQQISG 543
Cdd:COG1340    139 --------------------------VEKIKELE-KELEKAK---KALEKNEKLKELRAELKELRKEAEEIHKKIKELAE 188

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1804876928  544 RLQDVRLRKQTQKTEIEVLDKQCDLEIMEIKQLQQELQDYQNKLIYLVPEKQLLNERIKNMQLGNTPDlgidllhKKSLE 623
Cdd:COG1340    189 EAQELHEEMIELYKEADELRKEADELHKEIVEAQEKADELHEEIIELQKELRELRKELKKLRKKQRAL-------KREKE 261

                          250
                   ....*....|....*..
gi 1804876928  624 KEELCQRLKEQLDALEK 640
Cdd:COG1340    262 KEELEEKAEEIFEKLKK 278

Src Homology 3 domain of Class A and B Dedicator of Cytokinesis proteins; DOCK proteins are atypical guanine nucleotide exchange factors (GEFs) that lack the conventional Dbl homology (DH) domain. They are divided into four classes (A-D) based on sequence similarity and domain architecture: class A includes Dock1, 2 and 5; class B includes Dock3 and 4; class C includes Dock6, 7, and 8; and class D includes Dock9, 10 and 11. All DOCKs contain two homology domains: the DHR-1 (Dock homology region-1), also called CZH1 (CED-5, Dock180, and MBC-zizimin homology 1), and DHR-2 (also called CZH2 or Docker). The DHR-1 domain binds phosphatidylinositol-3,4,5-triphosphate while DHR-2 contains the catalytic activity for Rac and/or Cdc42. This subfamily includes only Class A and B DOCKs, which also contain an SH3 domain at the N-terminal region and a PxxP motif at the C-terminus. Class A/B DOCKs are mostly specific GEFs for Rac, except Dock4 which activates the Ras family GTPase Rap1, probably indirectly through interaction with Rap regulatory proteins. The SH3 domain of class A/B DOCKs have been shown to bind Elmo, a scaffold protein that promotes GEF activity of DOCKs by releasing DHR-2 autoinhibition by the intramolecular SH3 domain. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212805 [Multi-domain] Cd Length: 56 Bit Score: 39.87 E-value: 3.85e-04

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|.
gi 1804876928 1085 YVASGSEQLSLAPGQLILILKKNSsGWWQGELQarGKKRQKGWFPASHVKL 1135
Cdd:cd11872      8 FQGDGEHQLSLQVGDTVQILEECE-GWYRGFSL--RNKSLKGIFPKSYVHI 55

Fourth Src homology 3 domain (or SH3D) of Intersectin-2; Intersectin-2 (ITSN2) is an adaptor protein that functions in exo- and endocytosis, actin cytoskeletal reorganization, and signal transduction. It plays a role in clathrin-coated pit (CCP) formation. It binds to many proteins through its multidomain structure and facilitate the assembly of multimeric complexes. ITSN2 also functions as a specific GEF for Cdc42 activation in epithelial morphogenesis, and is required in mitotic spindle orientation. It exists in alternatively spliced short and long isoforms. The short isoform contains two Eps15 homology domains (EH1 and EH2), a coiled-coil region and five SH3 domains (SH3A-E), while the long isoform, in addition, contains RhoGEF (also called Dbl-homologous or DH), Pleckstrin homology (PH) and C2 domains. The fourth SH3 domain (or SH3D) of ITSN2 is expected to bind protein partners, similar to ITSN1 which has been shown to bind SHIP2, Numb, CdGAP, and N-WASP. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212927 Cd Length: 59 Bit Score: 40.30 E-value: 3.96e-04

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....*...
gi 1804876928  924 AQALCSWTAKKDNHLNFSKHDIITVLEQQEN-WWFGEVHG-----GRGWFPKSYVKII 975
Cdd:cd11994      2 AQVTTAYVASGVEQLSLSPGQLILILKKNSSgWWLGELQArgkkrQKGWFPASHVKLL 59

Uncharacterized conserved protein, contains a C-terminal ATPase domain [Function unknown];

Pssm-ID: 443941 [Multi-domain] Cd Length: 1089 Bit Score: 45.29 E-value: 4.00e-04

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1804876928  417 RRQALMEQQQREAERKAQKEKEEWERKQRELQEQEwkkqlELEKRLEKQrelerqreeerrkeierreaakqelERQRRL 496
Cdd:COG4913    241 HEALEDAREQIELLEPIRELAERYAAARERLAELE-----YLRAALRLW-------------------------FAQRRL 290

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1804876928  497 EWERIRRQELLNQRNREQEEIVRLNSKKKSLHLELEALNGKHQQISGRlqdvrlRKQTQKTEIEVLDKqcdleimEIKQL 576
Cdd:COG4913    291 ELLEAELEELRAELARLEAELERLEARLDALREELDELEAQIRGNGGD------RLEQLEREIERLER-------ELEER 357

                          170       180       190       200       210       220       230
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|...
gi 1804876928  577 QQELQDYQNKLIYL---VP--EKQLLNERIKNMQLGNTPDLGIDLLHKKSLEKEELCQRLKEQLDALEKETAS 644
Cdd:COG4913    358 ERRRARLEALLAALglpLPasAEEFAALRAEAAALLEALEEELEALEEALAEAEAALRDLRRELRELEAEIAS 430

Src homology 3 domain of ArfGAP with SH3 domain, ankyrin repeat and PH domain containing proteins; ASAPs are Arf GTPase activating proteins (GAPs) and they function in regulating cell growth, migration, and invasion. They contain an N-terminal BAR domain, followed by a Pleckstrin homology (PH) domain, an Arf GAP domain, ankyrin (ANK) repeats, and a C-terminal SH3 domain. Vertebrates contain at least three members, ASAP1, ASAP2, and ASAP3, but some ASAP3 proteins do not seem to harbor a C-terminal SH3 domain. ASAP1 and ASAP2 show GTPase activating protein (GAP) activity towards Arf1 and Arf5. They do not show GAP activity towards Arf6, but are able to mediate Arf6 signaling by binding stably to GTP-Arf6. ASAP3 is an Arf6-specific GAP. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212755 [Multi-domain] Cd Length: 53 Bit Score: 39.99 E-value: 4.08e-04

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|...
gi 1804876928  786 KALYRFEARSHDEMSFNSGDIIQVDEKtiGEPGWLYGSFQG---NFGWFPCNY 835
Cdd:cd11821      3 RALYDCQADNDDELTFSEGEIIVVTGE--EDDEWWEGHIEGdpsRRGVFPVSF 53

Third (or C-terminal) Src Homology 3 domain of Vinexin, also called Sorbin and SH3 domain containing 3 (Sorbs3); Vinexin is also called Sorbs3, SH3P3, and SH3-containing adapter molecule 1 (SCAM-1). It is an adaptor protein containing one sorbin homology (SoHo) and three SH3 domains. Vinexin was first identified as a vinculin binding protein; it is co-localized with vinculin at cell-ECM and cell-cell adhesion sites. There are several splice variants of vinexin: alpha, which contains the SoHo and three SH3 domains and displays tissue-specific expression; and beta, which contains only the three SH3 domains and is widely expressed. Vinexin alpha stimulates the accumulation of F-actin at focal contact sites. Vinexin also promotes keratinocyte migration and wound healing. The SH3 domains of vinexin have been reported to bind a number of ligands including vinculin, WAVE2, DLG5, Abl, and Cbl. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212851 [Multi-domain] Cd Length: 58 Bit Score: 39.94 E-value: 4.18e-04

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....*...
gi 1804876928 1004 GDEYIALYSYSSVEPGDLTFIEGEEILVTQK-DGEWWTGsIGDRT---GIFPSNYVKP 1057
Cdd:cd11918      1 RTPYKAVYQYRPQNEDELELREGDRVDVMQQcDDGWFVG-VSRRTqkfGTFPGNYVAP 57

Fourth Src homology 3 domain (or SH3D) of Intersectin; Intersectins (ITSNs) are adaptor proteins that function in exo- and endocytosis, actin cytoskeletal reorganization, and signal transduction. They are essential for initiating clathrin-coated pit formation. They bind to many proteins through their multidomain structure and facilitate the assembly of multimeric complexes. Vertebrates contain two ITSN proteins, ITSN1 and ITSN2, which exist in alternatively spliced short and long isoforms. The short isoforms contain two Eps15 homology domains (EH1 and EH2), a coiled-coil region and five SH3 domains (SH3A-E), while the long isoforms, in addition, contain RhoGEF (also called Dbl-homologous or DH), Pleckstrin homology (PH) and C2 domains. ITSN1 and ITSN2 are both widely expressed, with variations depending on tissue type and stage of development. The fourth SH3 domain (or SH3D) of ITSN1 has been shown to bind SHIP2, Numb, CdGAP, and N-WASP. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212773 [Multi-domain] Cd Length: 58 Bit Score: 40.01 E-value: 4.22e-04

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|.
gi 1804876928 1012 SYSSVEPGDLTFIEGEEILVTQKDGE-WWTGSIGDR-----TGIFPSNYVK 1056
Cdd:cd11839      7 PFTATAENQLSLAVGQLVLVRKKSPSgWWEGELQARgkkrqIGWFPANYVK 57

Src homology 3 domain of Abl Interactor 1; Abi1, also called e3B1, is a central regulator of actin cytoskeletal reorganization through interactions with many protein complexes. It is part of WAVE, a nucleation-promoting factor complex, that links Rac 1 activation to actin polymerization causing lamellipodia protrusion at the plasma membrane. Abi1 interact with formins to promote protrusions at the leading edge of motile cells. It also is a target of alpha4 integrin, regulating membrane protrusions at sites of integrin engagement. Abi proteins are adaptor proteins serving as binding partners and substrates of Abl tyrosine kinases. They are involved in regulating actin cytoskeletal reorganization and play important roles in membrane-ruffling, endocytosis, cell motility, and cell migration. Abi proteins contain a homeobox homology domain, a proline-rich region, and a SH3 domain. The SH3 domain of Abi binds to a PxxP motif in Abl. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212904 [Multi-domain] Cd Length: 59 Bit Score: 40.00 E-value: 4.27e-04

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|...
gi 1804876928  787 ALYRFEARSHDEMSFNSGDIIQVDEKTigEPGWLYGSFQGNFGWFPCNYVEKM 839
Cdd:cd11971      4 AIYDYSKDKDDELSFMEGAIIYVIKKN--DDGWYEGVCNGVTGLFPGNYVESI 54

Variant SH3 domain; SH3 (Src homology 3) domains are often indicative of a protein involved in signal transduction related to cytoskeletal organization. First described in the Src cytoplasmic tyrosine kinase. The structure is a partly opened beta barrel.

Pssm-ID: 429575 [Multi-domain] Cd Length: 54 Bit Score: 39.89 E-value: 4.28e-04

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....
gi 1804876928  785 YKALYRFEARSHDEMSFNSGDIIQVDEKtiGEPGWLYGSFQGNFGWFPCNYVEK 838
Cdd:pfam07653    2 GRVIFDYVGTDKNGLTLKKGDVVKVLGK--DNDGWWEGETGGRVGLVPSTAVEE 53

Third (or C-terminal) Src Homology 3 domain of Sorbin and SH3 domain containing 1 (Sorbs1), also called ponsin; Sorbs1 is also called ponsin, SH3P12, or CAP (c-Cbl associated protein). It is an adaptor protein containing one sorbin homology (SoHo) and three SH3 domains. It binds Cbl and plays a major role in regulating the insulin signaling pathway by enhancing insulin-induced phosphorylation of Cbl. Sorbs1, like vinexin, localizes at cell-ECM and cell-cell adhesion sites where it binds vinculin, paxillin, and afadin. It may function in the control of cell motility. Other interaction partners of Sorbs1 include c-Abl, Sos, flotillin, Grb4, ataxin-7, filamin C, among others. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212849 [Multi-domain] Cd Length: 59 Bit Score: 39.98 E-value: 4.31e-04

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....*
gi 1804876928 1007 YIALYSYSSVEPGDLTFIEGEEILVTQK-DGEWWTGSiGDRT---GIFPSNYVKP 1057
Cdd:cd11916      4 YQALYSYAPQNDDELELRDGDIVDVMEKcDDGWFVGT-SRRTkqfGTFPGNYVKL 57

Src homology 3 domain of RUN and SH3 domain-containing protein 2; RUSC2, also called Iporin or Interacting protein of Rab1, is expressed ubiquitously with highest amounts in the brain and testis. It interacts with the small GTPase Rab1 and the Golgi matrix protein GM130, and may function in linking GTPases to certain intracellular signaling pathways. RUSC proteins are adaptor proteins consisting of RUN, leucine zipper, and SH3 domains. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212890 Cd Length: 52 Bit Score: 39.90 E-value: 4.41e-04

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|.
gi 1804876928 1152 QVIAMYDYVANNEDELNFSKGQLINVLNKDDPDWWQGEINGVTGLFPSNYV 1202
Cdd:cd11957      1 EVKALCHHIATEPGQLSFNKGDILQVLSRADGDWLRCSLGPDSGLVPIAYV 51

C-terminal (or second) Src Homology 3 domain of the p67phox subunit of NADPH oxidase; p67phox, also called Neutrophil cytosol factor 2 (NCF-2), is a cytosolic subunit of the phagocytic NADPH oxidase complex (also called Nox2 or gp91phox) which plays a crucial role in the cellular response to bacterial infection. NADPH oxidase catalyzes the transfer of electrons from NADPH to oxygen during phagocytosis forming superoxide and reactive oxygen species. p67phox plays a regulatory role and contains N-terminal TPR, first SH3 (or N-terminal or central SH3), PB1, and C-terminal SH3 domains. It binds, via its C-terminal SH3 domain, to a proline-rich region of p47phox and upon activation, this complex assembles with flavocytochrome b558, the Nox2-p22phox heterodimer. Concurrently, RacGTP translocates to the membrane and interacts with the TPR domain of p67phox, which leads to the activation of NADPH oxidase. The PB1 domain of p67phox binds to its partner PB1 domain in p40phox, and this facilitates the assembly of p47phox-p67phox at the membrane. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212979 [Multi-domain] Cd Length: 53 Bit Score: 39.79 E-value: 4.43e-04

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|.
gi 1804876928  787 ALYRFEARSHDEMSFNSGDIIQVDEKTIGEpgWLYGSFQGNFGWFPCNYVE 837
Cdd:cd12046      4 ALFSYEASQPEDLEFQKGDVILVLSKVNED--WLEGQCKGKIGIFPSAFVE 52

DNA double-strand break repair Rad50 ATPase;

Pssm-ID: 179385 [Multi-domain] Cd Length: 880 Bit Score: 45.03 E-value: 4.51e-04

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1804876928  400 EDKRKANYERGNVE--LEKRRQALmEQQQREAERKAQKEKEE----WERKQRELQEqewkkqlELEkRLEKQRelerqre 473
Cdd:PRK02224   166 EYRERASDARLGVErvLSDQRGSL-DQLKAQIEEKEEKDLHErlngLESELAELDE-------EIE-RYEEQR------- 229

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1804876928  474 eerrkeierREAAKQELERQRRLEWERIRRQELlnqrNREQEEIVRLNSKKKSLHLELEALngkhqqiSGRLQDVRLRKQ 553
Cdd:PRK02224   230 ---------EQARETRDEADEVLEEHEERREEL----ETLEAEIEDLRETIAETEREREEL-------AEEVRDLRERLE 289

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1804876928  554 TQKTEIEVLDKQCDLEIMEIKQLQQELQDYQNKLIYLvpEKQLLNERIKNMQLGNTpdlgIDLLHKKSLEKEELCQRLKE 633
Cdd:PRK02224   290 ELEEERDDLLAEAGLDDADAEAVEARREELEDRDEEL--RDRLEECRVAAQAHNEE----AESLREDADDLEERAEELRE 363

                          250       260       270       280       290       300       310       320
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1804876928  634 QLDALEKETASKLSEMDSFNNQLKcgNMDDSvlqcllsllsclnnlfllLKELRESYN---TQQLALEQLHKIKRDKLKE 710
Cdd:PRK02224   364 EAAELESELEEAREAVEDRREEIE--ELEEE------------------IEELRERFGdapVDLGNAEDFLEELREERDE 423

                          330       340       350       360       370       380       390       400
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1804876928  711 IERKRSELIQKKKLEDEAIRKAKQ----GK--------ENLWRESLRKEEEEKQKRLQEEKTQEKVQEEERkveEKQCEP 778
Cdd:PRK02224   424 LREREAELEATLRTARERVEEAEAlleaGKcpecgqpvEGSPHVETIEEDRERVEELEAELEDLEEEVEEV---EERLER 500


                   ....*
gi 1804876928  779 ASALV 783
Cdd:PRK02224   501 AEDLV 505

Src homology 3 domain of RUN and SH3 domain-containing proteins 1 and 2; RUSC1 and RUSC2, that were originally characterized in silico. They are adaptor proteins consisting of RUN, leucine zipper, and SH3 domains. RUSC1, also called NESCA (New molecule containing SH3 at the carboxy-terminus), is highly expressed in the brain and is translocated to the nuclear membrane from the cytoplasm upon stimulation with neurotrophin. It plays a role in facilitating neurotrophin-dependent neurite outgrowth. It also interacts with NEMO (or IKKgamma) and may function in NEMO-mediated activation of NF-kB. RUSC2, also called Iporin, is expressed ubiquitously with highest amounts in the brain and testis. It interacts with the small GTPase Rab1 and the Golgi matrix protein GM130, and may function in linking GTPases to certain intracellular signaling pathways. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212744 Cd Length: 50 Bit Score: 39.73 E-value: 4.60e-04

                           10        20        30        40
                   ....*....|....*....|....*....|....*....|....*....
gi 1804876928 1153 VIAMYDYVANNEDELNFSKGQLINVLNKDDPDWWQGEINGVTGLFPSNY 1201
Cdd:cd11810      2 VRALCHHVATDSGQLSFRKGDILRVIARVDDDWLLCTRGSTKGLVPLSY 50

Src homology 3 domain of ArfGAP with SH3 domain, ankyrin repeat and PH domain containing proteins; ASAPs are Arf GTPase activating proteins (GAPs) and they function in regulating cell growth, migration, and invasion. They contain an N-terminal BAR domain, followed by a Pleckstrin homology (PH) domain, an Arf GAP domain, ankyrin (ANK) repeats, and a C-terminal SH3 domain. Vertebrates contain at least three members, ASAP1, ASAP2, and ASAP3, but some ASAP3 proteins do not seem to harbor a C-terminal SH3 domain. ASAP1 and ASAP2 show GTPase activating protein (GAP) activity towards Arf1 and Arf5. They do not show GAP activity towards Arf6, but are able to mediate Arf6 signaling by binding stably to GTP-Arf6. ASAP3 is an Arf6-specific GAP. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212755 [Multi-domain] Cd Length: 53 Bit Score: 39.61 E-value: 4.73e-04

                           10        20        30        40
                   ....*....|....*....|....*....|....*....|....*.
gi 1804876928 1086 VASGSEQLSLAPGQLILILKKNSSGWWQGELQarGKKRQKGWFPAS 1131
Cdd:cd11821      9 QADNDDELTFSEGEIIVVTGEEDDEWWEGHIE--GDPSRRGVFPVS 52

Src Homology 3 (SH3) domain of Inhibitor of ASPP protein (iASPP); iASPP, also called RelA-associated inhibitor (RAI), is an oncoprotein that inhibits the apoptotic transactivation potential of p53. It is upregulated in human breast cancers expressing wild-type p53, in acute leukemias regardless of the p53 mutation status, as well as in ovarian cancer where it is associated with poor patient outcome and chemoresistance. iASPP is also a binding partner and negative regulator of p65RelA, which promotes cell proliferation and inhibits apoptosis; p65RelA has the opposite effect on cell growth compared to the p53 family. It contains a proline-rich region, four ankyrin (ANK) repeats, and an SH3 domain at its C-terminal half. The SH3 domain and the ANK repeats of iASPP contribute to the p53 binding site; they bind to the DNA binding domain of p53. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212885 [Multi-domain] Cd Length: 56 Bit Score: 39.91 E-value: 4.83e-04

                           10        20        30        40
                   ....*....|....*....|....*....|....*....|....*....
gi 1804876928  926 ALCSWTAKKDNHLNFSKHDIITVLE---QQENWWFGEVHGGRGWFPKSY 971
Cdd:cd11952      5 ALWDYSAEFPDELSFKEGDMVTVLRkdgEGTDWWWASLCGREGYVPRNY 53

Second Src homology 3 domain of Tyrosine kinase substrate (Tks) proteins; Tks proteins are Src substrates and scaffolding proteins that play important roles in the formation of podosomes and invadopodia, the dynamic actin-rich structures that are related to cell migration and cancer cell invasion. Vertebrates contain two Tks proteins, Tks4 (Tyr kinase substrate with four SH3 domains) and Tks5 (Tyr kinase substrate with five SH3 domains), which display partially overlapping but non-redundant functions. Both associate with the ADAMs family of transmembrane metalloproteases, which function as sheddases and mediators of cell and matrix interactions. Tks5 interacts with N-WASP and Nck, while Tks4 is essential for the localization of MT1-MMP (membrane-type 1 matrix metalloproteinase) to invadopodia. Tks proteins contain an N-terminal Phox homology (PX) domain and four or five SH3 domains. This model characterizes the second SH3 domain of Tks proteins. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212949 Cd Length: 54 Bit Score: 39.75 E-value: 4.85e-04

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....
gi 1804876928 1081 VTSAYVASGSEQLSLAPGQLILILKKNSSGWWQGELQARgkkrqKGWFPASHVK 1134
Cdd:cd12016      5 TTQAYKAENEDEIGFETGVVVEVIQKNLDGWWKIRYQGK-----EGWAPATYLK 53

Mitotic checkpoint protein; This family consists of several eukaryotic mitotic checkpoint (Mitotic arrest deficient or MAD) proteins. The mitotic spindle checkpoint monitors proper attachment of the bipolar spindle to the kinetochores of aligned sister chromatids and causes a cell cycle arrest in prometaphase when failures occur. Multiple components of the mitotic spindle checkpoint have been identified in yeast and higher eukaryotes. In S.cerevisiae, the existence of a Mad1-dependent complex containing Mad2, Mad3, Bub3 and Cdc20 has been demonstrated.

Pssm-ID: 461677 [Multi-domain] Cd Length: 660 Bit Score: 44.73 E-value: 4.98e-04

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1804876928  411 NVELEKRRQALMEQQQR-EAERKAQKEKEEWERKQRELQEQEWKKQLeLEKRLEKQRELERQREEERRKEIERREAAKQE 489
Cdd:pfam05557   13 QLQNEKKQMELEHKRARiELEKKASALKRQLDRESDRNQELQKRIRL-LEKREAEAEEALREQAELNRLKKKYLEALNKK 91

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1804876928  490 LERQRRLEWERIRRQELLNQRNRE-QEEIVRLNSKKKSLHLELEALNGKHQQISGRLQDV-RLRKQTQKTEIEVLDKQcd 567
Cdd:pfam05557   92 LNEKESQLADAREVISCLKNELSElRRQIQRAELELQSTNSELEELQERLDLLKAKASEAeQLRQNLEKQQSSLAEAE-- 169

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1804876928  568 leiMEIKQLQQELQDY-QNKLIY--------LVPEKQLLNERIK--NMQLgNTPDLGIDLLH------KKSLEKEElcqR 630
Cdd:pfam05557  170 ---QRIKELEFEIQSQeQDSEIVknskselaRIPELEKELERLRehNKHL-NENIENKLLLKeevedlKRKLEREE---K 242

                          250       260       270       280       290       300       310       320
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1804876928  631 LKEQLDALEKETASKLSEMDSFNN--QLKCGNMDDSVLQCLLSLLSCLNNlfLLLKELRESYNTQqlaLEQLHKIKRDKL 708
Cdd:pfam05557  243 YREEAATLELEKEKLEQELQSWVKlaQDTGLNLRSPEDLSRRIEQLQQRE--IVLKEENSSLTSS---ARQLEKARRELE 317

                          330       340       350       360       370
                   ....*....|....*....|....*....|....*....|....*....|....*...
gi 1804876928  709 KEIerkrseLIQKKKLEDEAIRkakqgkenlwreslRKEEEEKQKRLQEEK---TQEK 763
Cdd:pfam05557  318 QEL------AQYLKKIEDLNKK--------------LKRHKALVRRLQRRVlllTKER 355

Uncharacterized conserved protein YhaN, contains AAA domain [Function unknown];

Pssm-ID: 443752 [Multi-domain] Cd Length: 641 Bit Score: 44.76 E-value: 5.18e-04

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1804876928  413 ELEKRRQALMEQQQ--REAERKAQKEKEEWERKQRELQEQEWKKQLELEKRLEKQRELERQREEERRKEIERREAAKQEL 490
Cdd:COG4717    143 ELPERLEELEERLEelRELEEELEELEAELAELQEELEELLEQLSLATEEELQDLAEELEELQQRLAELEEELEEAQEEL 222

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1804876928  491 ERQRRlEWERIRRQELLNQRNREQEE------------------------------------------IVRLNSKKKSLH 528
Cdd:COG4717    223 EELEE-ELEQLENELEAAALEERLKEarlllliaaallallglggsllsliltiagvlflvlgllallFLLLAREKASLG 301

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1804876928  529 LELEALNG-------KHQQISGRLQDVRLRKQTQKTEIEVLDKQCDleimEIKQLQQELQDYQNKLiylvPEKQLLNERI 601
Cdd:COG4717    302 KEAEELQAlpaleelEEEELEELLAALGLPPDLSPEELLELLDRIE----ELQELLREAEELEEEL----QLEELEQEIA 373

                          250       260       270       280       290       300       310       320
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1804876928  602 KNMQLGNTPDLGiDLLHKksLEKEELCQRLKEQLDALEKETASKLSEMdsfNNQLKCGNMDDsvlqcllsllsclnnlfl 681
Cdd:COG4717    374 ALLAEAGVEDEE-ELRAA--LEQAEEYQELKEELEELEEQLEELLGEL---EELLEALDEEE------------------ 429

                          330       340       350       360       370       380       390       400
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1804876928  682 lLKELRESYNTQQLALEQLHKIKRDKLKEIERKRSELiqkkkLEDEAIRKAKQGKENLWRESLRKEEEEKQKRLQE---E 758
Cdd:COG4717    430 -LEEELEELEEELEELEEELEELREELAELEAELEQL-----EEDGELAELLQELEELKAELRELAEEWAALKLALellE 503


                   ....*....
gi 1804876928  759 KTQEKVQEE 767
Cdd:COG4717    504 EAREEYREE 512

First Src homology 3 domain of Tyrosine kinase substrate (Tks) proteins; Tks proteins are Src substrates and scaffolding proteins that play important roles in the formation of podosomes and invadopodia, the dynamic actin-rich structures that are related to cell migration and cancer cell invasion. Vertebrates contain two Tks proteins, Tks4 (Tyr kinase substrate with four SH3 domains) and Tks5 (Tyr kinase substrate with five SH3 domains), which display partially overlapping but non-redundant functions. Both associate with the ADAMs family of transmembrane metalloproteases, which function as sheddases and mediators of cell and matrix interactions. Tks5 interacts with N-WASP and Nck, while Tks4 is essential for the localization of MT1-MMP (membrane-type 1 matrix metalloproteinase) to invadopodia. Tks proteins contain an N-terminal Phox homology (PX) domain and four or five SH3 domains. This model characterizes the first SH3 domain of Tks proteins. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212948 Cd Length: 53 Bit Score: 39.71 E-value: 5.20e-04

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|..
gi 1804876928 1081 VTSAYVASGSEQLSLAPGQLILILKKNSSGWWQGELQargkkRQKGWFPASH 1132
Cdd:cd12015      4 VVADYKKQQPNEISLRAGDVVDVIEKNENGWWFVSLE-----DEQGWVPATY 50

Chromosome segregation protein NDC80, interacts with SMC proteins [Cell cycle control, cell division, chromosome partitioning];

Pssm-ID: 444066 [Multi-domain] Cd Length: 594 Bit Score: 44.95 E-value: 5.23e-04

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1804876928  491 ERQRRLEWERIRRQELLNQRNREQEEIVRLNSKKKSLHLELEALNGKHQQISgRLQDVRLRKQTQKTEIEVLDkqcdlEI 570
Cdd:COG5185    155 EVETGIIKDIFGKLTQELNQNLKKLEIFGLTLGLLKGISELKKAEPSGTVNS-IKESETGNLGSESTLLEKAK-----EI 228

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1804876928  571 MEIKQLQQELQDYQNKLIYLvpekQLLNERIKNMQLGNTpdlgiDLLHKKSLEKEELCQRLKEQLDALEKE---TASKLS 647
Cdd:COG5185    229 INIEEALKGFQDPESELEDL----AQTSDKLEKLVEQNT-----DLRLEKLGENAESSKRLNENANNLIKQfenTKEKIA 299

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1804876928  648 EmdsfnnqlkcgNMDDSVLQCLLSLLSCLNNLFLLLKEL----RESYNTQQLALEQLHKIKRDKLKEIERKRSELIQKKK 723
Cdd:COG5185    300 E-----------YTKSIDIKKATESLEEQLAAAEAEQELeeskRETETGIQNLTAEIEQGQESLTENLEAIKEEIENIVG 368

                          250       260       270       280       290       300       310
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|.
gi 1804876928  724 LEDEAIRKAKQGKENLWRESLRKEEEEKQKRlQEEKTQEKVQ-------EEERKVEEKQCEPASALVNYKA 787
Cdd:COG5185    369 EVELSKSSEELDSFKDTIESTKESLDEIPQN-QRGYAQEILAtledtlkAADRQIEELQRQIEQATSSNEE 438

Second Src Homology 3 domain (SH3B) of Cbl-interacting protein of 85 kDa; CIN85, also called SH3 domain-containing kinase-binding protein 1 (SH3KBP1) or CD2-binding protein 3 (CD2BP3) or Ruk, is an adaptor protein that is involved in the downregulation of receptor tyrosine kinases by facilitating endocytosis through interaction with endophilin-associated ubiquitin ligase Cbl proteins. It is also important in many other cellular processes including vesicle-mediated transport, cytoskeletal remodelling, apoptosis, cell adhesion and migration, and viral infection, among others. CIN85 exists as multiple variants from alternative splicing; the main variant contains three SH3 domains, a proline-rich region, and a C-terminal coiled-coil domain. All of these domains enable CIN85 to bind various protein partners and assemble complexes that have been implicated in many different functions. This alignment model represents the second SH3 domain (SH3B) of CIN85. SH3B has been shown to bind Cbl proline-rich peptides and ubiquitin. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212988 [Multi-domain] Cd Length: 53 Bit Score: 39.59 E-value: 5.25e-04

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|..
gi 1804876928  923 KAQALCSWTAKKDNHLNFSKHDIITVL-EQQENWWFGEVHGGRGWFPKSYVK 973
Cdd:cd12055      1 RCQVAFSYLPQNEDELELKVGDIIEVVgEVEEGWWEGVLNGKTGMFPSNFIK 52

Second Src homology 3 domain of Tyrosine kinase substrate with five SH3 domains; Tks5, also called SH3 and PX domain-containing protein 2A (SH3PXD2A) or Five SH (FISH), is a scaffolding protein and Src substrate that is localized in podosomes, which are electron-dense structures found in Src-transformed fibroblasts, osteoclasts, macrophages, and some invasive cancer cells. It binds and regulates some members of the ADAMs family of transmembrane metalloproteases, which function as sheddases and mediators of cell and matrix interactions. It is required for podosome formation, degradation of the extracellular matrix, and cancer cell invasion. Tks5 contains an N-terminal Phox homology (PX) domain and five SH3 domains. This model characterizes the second SH3 domain of Tks5. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 213010 Cd Length: 54 Bit Score: 39.63 E-value: 5.26e-04

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|.
gi 1804876928 1084 AYVASGSEQLSLAPGQLILILKKNSSGWWQgeLQARGKkrqKGWFPASHVK 1134
Cdd:cd12077      8 PYTSQGKDEIGFEKGVTVEVIQKNLEGWWY--IRYLGK---EGWAPASYLK 53

C-terminal Src Homology 3 domain of Ct10 Regulator of Kinase adaptor proteins; CRK adaptor proteins consists of SH2 and SH3 domains, which bind tyrosine-phosphorylated peptides and proline-rich motifs, respectively. They function downstream of protein tyrosine kinases in many signaling pathways started by various extracellular signals, including growth and differentiation factors. Cellular CRK (c-CRK) contains a single SH2 domain, followed by N-terminal and C-terminal SH3 domains. It is involved in the regulation of many cellular processes including cell growth, motility, adhesion, and apoptosis. CRK has been implicated in the malignancy of various human cancers. The C-terminal SH3 domain of CRK has not been shown to bind any target protein; it acts as a negative regulator of CRK function by stabilizing a structure that inhibits the access by target proteins to the N-terminal SH3 domain. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes by intramolecular interactions, changing the subcellular localization of signal pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212693 [Multi-domain] Cd Length: 57 Bit Score: 39.78 E-value: 5.39e-04

                           10        20        30        40        50        60
                   ....*....|....*....|....*....|....*....|....*....|....*....|..
gi 1804876928 1076 PEIAQVTSAYV--ASGSEQLSLAPGQLILILKKNSSGWWQGELqaRGKkrqKGWFPASHVKL 1135
Cdd:cd11759      1 PAYARVIQKRVpnAYDKTALALEVGDLVKVTKINVSGQWEGEL--NGK---VGHFPFTHVEL 57

Second Src homology 3 domain of Tyrosine kinase substrate with five SH3 domains; Tks5, also called SH3 and PX domain-containing protein 2A (SH3PXD2A) or Five SH (FISH), is a scaffolding protein and Src substrate that is localized in podosomes, which are electron-dense structures found in Src-transformed fibroblasts, osteoclasts, macrophages, and some invasive cancer cells. It binds and regulates some members of the ADAMs family of transmembrane metalloproteases, which function as sheddases and mediators of cell and matrix interactions. It is required for podosome formation, degradation of the extracellular matrix, and cancer cell invasion. Tks5 contains an N-terminal Phox homology (PX) domain and five SH3 domains. This model characterizes the second SH3 domain of Tks5. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 213010 Cd Length: 54 Bit Score: 39.63 E-value: 5.52e-04

                           10        20        30        40
                   ....*....|....*....|....*....|....*....|....*
gi 1804876928  930 WTAKKDNHLNFSKHDIITVLEQQ-ENWWFGEVHGGRGWFPKSYVK 973
Cdd:cd12077      9 YTSQGKDEIGFEKGVTVEVIQKNlEGWWYIRYLGKEGWAPASYLK 53

Uncharacterized coiled-coil protein, contains DUF342 domain [Function unknown];

Pssm-ID: 440951 [Multi-domain] Cd Length: 297 Bit Score: 44.13 E-value: 5.62e-04

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1804876928  522 SKKKSLHLELEALNGKHQQISGRLQDVRLRKQTQKTEIEVLDKQCDLEIMEIKQLQQELQDYQNKliylvpeKQLLNERI 601
Cdd:COG1340      1 SKTDELSSSLEELEEKIEELREEIEELKEKRDELNEELKELAEKRDELNAQVKELREEAQELREK-------RDELNEKV 73

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1804876928  602 KnmqlgntpdlgidllhkkslekeelcqRLKEQLDALEKETASKLSEMDSFNNQLKCGNMD----DSV----------LQ 667
Cdd:COG1340     74 K---------------------------ELKEERDELNEKLNELREELDELRKELAELNKAggsiDKLrkeierlewrQQ 126

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1804876928  668 CLLSLLSCLNNLFLLLKELRESYNTQQLALEQLHKIK--RDKLKEIERKRSELIQKKKledEAIRKAKQGKENLW----- 740
Cdd:COG1340    127 TEVLSPEEEKELVEKIKELEKELEKAKKALEKNEKLKelRAELKELRKEAEEIHKKIK---ELAEEAQELHEEMIelyke 203

                          250       260       270
                   ....*....|....*....|....*....|....*
gi 1804876928  741 RESLRKEEEEKQKRLQEekTQEKVQEEERKVEEKQ 775
Cdd:COG1340    204 ADELRKEADELHKEIVE--AQEKADELHEEIIELQ 236

Src homology 3 domain of Endophilin-B; Endophilins play roles in synaptic vesicle formation, virus budding, mitochondrial morphology maintenance, receptor-mediated endocytosis inhibition, and endosomal sorting. They are classified into two types, A and B. Vertebrates contain two endophilin-B isoforms. Endophilin-B proteins are cytoplasmic proteins expressed mainly in the heart, placenta, and skeletal muscle. Endophilins contain an N-terminal N-BAR domain (BAR domain with an additional N-terminal amphipathic helix), followed by a variable region containing proline clusters, and a C-terminal SH3 domain. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212736 [Multi-domain] Cd Length: 52 Bit Score: 39.58 E-value: 5.66e-04

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|..
gi 1804876928  923 KAQALCSWTAKKDNHLNFSKHDIITVLE---QQENWWFGEVHGGRGWFPKSY 971
Cdd:cd11802      1 KARVLYDYDAEDSTELSLLADEVITVYElpgMDEDYMMGERGSQRGKVPVAY 52

Src homology 3 domain of APC-Stimulated guanine nucleotide Exchange Factor 2; ASEF2, also called Spermatogenesis-associated protein 13 (SPATA13), is a GEF that localizes with actin at the leading edge of cells and is important in cell migration and adhesion dynamics. GEFs activate small GTPases by exchanging bound GDP for free GTP. ASEF2 can activate both Rac 1 and Cdc42, but only Rac1 activation is necessary for increased cell migration and adhesion turnover. Together with APC (adenomatous polyposis coli) and Neurabin2, a scaffold protein that binds F-actin, it is involved in regulating HGF-induced cell migration. ASEF2 contains a SH3 domain followed by RhoGEF (also called Dbl-homologous or DH) and Pleckstrin Homology (PH) domains. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212907 Cd Length: 54 Bit Score: 39.28 E-value: 6.20e-04

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|.
gi 1804876928 1085 YVASGSEQLSLAPGQLILILKKNSSGWWQGelqaRGKKRQkGWFPASHVKL 1135
Cdd:cd11974      9 HVTMDDQELAFKAGDVIRVLEASNKDWWWG----RNEDRE-AWFPASFVRL 54

C-terminal (or second) Src homology 3 domain of VAV3 protein; VAV3 is ubiquitously expressed and functions as a phosphorylation-dependent guanine nucleotide exchange factor (GEF) for RhoA, RhoG, and Rac1. It has been implicated to function in the hematopoietic, bone, cerebellar, and cardiovascular systems. VAV3 is essential in axon guidance in neurons that control blood pressure and respiration. It is overexpressed in prostate cancer cells and it plays a role in regulating androgen receptor transcriptional activity. VAV proteins contain several domains that enable their function: N-terminal calponin homology (CH), acidic, RhoGEF (also called Dbl-homologous or DH), Pleckstrin Homology (PH), C1 (zinc finger), SH2, and two SH3 domains. The SH3 domain of VAV is involved in the localization of proteins to specific sites within the cell, by interacting with proline-rich sequences within target proteins. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212911 [Multi-domain] Cd Length: 56 Bit Score: 39.62 E-value: 6.32e-04

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|..
gi 1804876928  924 AQALCSWTAKKDNHLNFSKHDIITVLEQQ--ENWWFGEVHGGRGWFPKSYVK 973
Cdd:cd11978      3 AIARYDFCARDMRELSLLKGDVVKIYTKMstNGWWRGEVNGRVGWFPSTYVE 54

Src homology 3 domain of SH3 and multiple ankyrin repeat domains (Shank) proteins; Shank proteins carry scaffolding functions through multiple sites of protein-protein interaction in its domain architecture, including ankyrin (ANK) repeats, a long proline rich region, as well as SH3, PDZ, and SAM domains. They bind a variety of membrane and cytosolic proteins, and exist in alternatively spliced isoforms. They are highly enriched in postsynaptic density (PSD) where they interact with the cytoskeleton and with postsynaptic membrane receptors including NMDA and glutamate receptors. They are crucial in the construction and organization of the PSD and dendritic spines of excitatory synapses. There are three members of this family (Shank1, Shank2, Shank3) which show distinct and cell-type specific patterns of expression. Shank1 is brain-specific; Shank2 is found in neurons, glia, endocrine cells, liver, and kidney; Shank3 is widely expressed. The SH3 domain of Shank binds GRIP, a scaffold protein that binds AMPA receptors and Eph receptors/ligands. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212766 Cd Length: 50 Bit Score: 39.34 E-value: 6.40e-04

                           10        20        30        40
                   ....*....|....*....|....*....|....*....|....*..
gi 1804876928 1007 YIALYSYSSVEPGDLTFIEGEEILVTQ-KDGEWWTGSIGDRTGIFPS 1052
Cdd:cd11832      2 FIAVKSYSPQEEGEISLHKGDRVKVLSiGEGGFWEGSVRGRTGWFPS 48

Src Homology 3 domain of Insulin Receptor tyrosine kinase Substrate p53; IRSp53 is also known as BAIAP2 (Brain-specific Angiogenesis Inhibitor 1-Associated Protein 2). It is a scaffolding protein that takes part in many signaling pathways including Cdc42-induced filopodia formation, Rac-mediated lamellipodia extension, and spine morphogenesis. IRSp53 exists as multiple splicing variants that differ mainly at the C-termini. One variant (T-form) is expressed exclusively in human breast cancer cells. The gene encoding IRSp53 is a putative susceptibility gene for Gilles de la Tourette syndrome. IRSp53 can also mediate the recruitment of effector proteins Tir and EspFu, which regulate host cell actin reorganization, to bacterial attachment sites. It contains an N-terminal IMD, a CRIB (Cdc42 and Rac interactive binding motif), an SH3 domain, and a WASP homology 2 (WH2) actin-binding motif at the C-terminus. The SH3 domain of IRSp53 has been shown to bind the proline-rich C-terminus of EspFu. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212848 Cd Length: 59 Bit Score: 39.61 E-value: 6.42e-04

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....*....
gi 1804876928  923 KAQALCSWTAKkDNH--LNFSKHDIITVL--EQQENWWFGEVHGG--RGWFPKSYVKII 975
Cdd:cd11915      2 RVQAIFSHAAG-DNStlLSFKEGDYITLLvpEARDGWHYGECEKTkmRGWFPFSYTRVL 59

Src homology 3 domain of Src kinase-like Protein Tyrosine Kinases; Src subfamily members include Src, Lck, Hck, Blk, Lyn, Fgr, Fyn, Yrk, Yes, and Brk. Src (or c-Src) proteins are cytoplasmic (or non-receptor) PTKs which are anchored to the plasma membrane. They contain an N-terminal SH4 domain with a myristoylation site, followed by SH3 and SH2 domains, a tyr kinase domain, and a regulatory C-terminal region containing a conserved tyr. They are activated by autophosphorylation at the tyr kinase domain, but are negatively regulated by phosphorylation at the C-terminal tyr by Csk (C-terminal Src Kinase). However, Brk lacks the N-terminal myristoylation sites. Src proteins are involved in signaling pathways that regulate cytokine and growth factor responses, cytoskeleton dynamics, cell proliferation, survival, and differentiation. They were identified as the first proto-oncogene products, and they regulate cell adhesion, invasion, and motility in cancer cells, and tumor vasculature, contributing to cancer progression and metastasis. Src kinases are overexpressed in a variety of human cancers, making them attractive targets for therapy. They are also implicated in acute inflammatory responses and osteoclast function. Src, Fyn, Yes, and Yrk are widely expressed, while Blk, Lck, Hck, Fgr, Lyn, and Brk show a limited expression pattern. This subfamily also includes Drosophila Src42A, Src oncogene at 42A (also known as Dsrc41) which accumulates at sites of cell-cell or cell-matrix adhesion, and participates in Drosphila development and wound healing. It has been shown to promote tube elongation in the tracheal system, is essential for proper cell-cell matching during dorsal closure, and regulates cell-cell contacts in developing Drosophila eyes. The SH3 domain of Src kinases contributes to substrate recruitment by binding adaptor proteins/substrates, and regulation of kinase activity through an intramolecular interaction. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212779 [Multi-domain] Cd Length: 52 Bit Score: 39.10 E-value: 6.52e-04

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....
gi 1804876928  784 NYKALYRFEARSHDEMSFNSGDIIQVDEKTIGEpgWLYGSFQ--GNFGWFPCNY 835
Cdd:cd11845      1 IYVALYDYEARTDDDLSFKKGDRLQILDDSDGD--WWLARHLstGKEGYIPSNY 52

Second Src Homology 3 domain of FCH and double SH3 domains protein 1; FCHSD1 has a domain structure consisting of an N-terminal F-BAR (FES-CIP4 Homology and Bin/Amphiphysin/Rvs), two SH3, and C-terminal proline-rich domains. It has only been characterized in silico and its function is unknown. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212828 Cd Length: 58 Bit Score: 39.56 E-value: 6.86e-04

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....*.
gi 1804876928  786 KALYRFEARSHDEMSFNSGDIIQVDEKTIGE--PGWLYGSFQGNFGWFPCNYVEKM 839
Cdd:cd11895      3 RALYSYTGQSPEELSFPEGALIRLLPRAQDGvdDGFWRGEFGGRVGVFPSLLVEEL 58

First Src Homology 3 domain of SH3 domain containing ring finger 2; SH3RF2 is also called POSHER (POSH-eliminating RING protein) or HEPP1 (heart protein phosphatase 1-binding protein). It acts as an anti-apoptotic regulator of the JNK pathway by binding to and promoting the degradation of SH3RF1 (or POSH), a scaffold protein that is required for pro-apoptotic JNK activation. It may also play a role in cardiac functions together with protein phosphatase 1. SH3RF2 contains an N-terminal RING finger domain and three SH3 domains. This model represents the first SH3 domain, located at the N-terminal half, of SH3RF2. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212862 Cd Length: 54 Bit Score: 39.15 E-value: 7.10e-04

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....*.
gi 1804876928  786 KALYRFEARSHDEMSFNSGDII----QVDEKtigepgWLYGSFQGNFGWFPCNYVE 837
Cdd:cd11929      4 KALCNYRGHNPGDLKFNKGDVIllrrQLDEN------WYLGEINGVSGIFPASSVE 53

recombination and DNA strand exchange inhibitor protein; Reviewed

Pssm-ID: 234750 [Multi-domain] Cd Length: 782 Bit Score: 44.43 E-value: 7.11e-04

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1804876928  682 LLKELRESYNTQQLALEQLHKIKRDKLKEIERKRSELIQKKKLE-DEAIRKAKQGKENLWRESLRKEEEEKQKRLQE--E 758
Cdd:PRK00409   542 LLKEAEKLKEELEEKKEKLQEEEDKLLEEAEKEAQQAIKEAKKEaDEIIKELRQLQKGGYASVKAHELIEARKRLNKanE 621

                           90
                   ....*....|....*..
gi 1804876928  759 KTQEKVQEEERKVEEKQ 775
Cdd:PRK00409   622 KKEKKKKKQKEKQEELK 638

First C-terminal Src homology 3 domain of SH3 and cysteine-rich domain-containing protein 3 (Stac3); Stac proteins are putative adaptor proteins that contain a cysteine-rich C1 domain and one or two SH3 domains at the C-terminus. There are three mammalian members (Stac1, Stac2, and Stac3) of this family. Stac1 and Stac3 contain two SH3 domains while Stac2 contains a single SH3 domain at the C-terminus. Stac1 and Stac2 have been found to be expressed differently in mature dorsal root ganglia (DRG) neurons. Stac1 is mainly expressed in peptidergic neurons while Stac2 is found in a subset of nonpeptidergic and all trkB+ neurons. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212919 [Multi-domain] Cd Length: 53 Bit Score: 39.12 E-value: 7.28e-04

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|..
gi 1804876928  785 YKALYRFEARSHDEMSFNSGDIIQVDEKTIGEpgWLYGSFQGNFGWFPCNYV 836
Cdd:cd11986      2 FVALYRFKALEKDDLDFHPGERITVIDDSNEE--WWRGKIGEKTGYFPMNFI 51

Src Homology 3 domain of Src Kinase-Associated Phosphoprotein 1 and similar proteins; This subfamily is composed of SKAP1, SKAP2, and similar proteins. SKAP1 and SKAP2 are immune cell-specific adaptor proteins that play roles in T- and B-cell adhesion, respectively, and are thus important in the migration of T- and B-cells to sites of inflammation and for movement during T-cell conjugation with antigen-presenting cells. Both SKAP1 and SKAP2 bind to ADAP (adhesion and degranulation-promoting adaptor protein), among many other binding partners. They contain a pleckstrin homology (PH) domain, a C-terminal SH3 domain, and several tyrosine phosphorylation sites. The SH3 domain of SKAP1 is necessary for its ability to regulate T-cell conjugation with antigen-presenting cells and the formation of LFA-1 clusters. SKAP1 binds primarily to a proline-rich region of ADAP through its SH3 domain; its degradation is regulated by ADAP. A secondary interaction occurs via the ADAP SH3 domain and the RKxxYxxY motif in SKAP1. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212800 Cd Length: 53 Bit Score: 38.95 E-value: 7.35e-04

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|.
gi 1804876928  925 QALCSWTAKKDNHLNFSKHDIITVLEQQEN---WWFGEVHGGRGWFPKSYV 972
Cdd:cd11866      3 MGLWDCSGNEPDELSFKRGDLIYIISKEYDsfgWWVGELNGKVGLVPKDYL 53

Src Homology 3 domain of Sorting nexin 18; SNX18 is localized to peripheral endosomal structures, and acts in a trafficking pathway that is clathrin-independent but relies on AP-1 and PACS1. It binds FIP5 and is required for apical lumen formation. It may also play a role in axonal elongation. SNXs are Phox homology (PX) domain containing proteins that are involved in regulating membrane traffic and protein sorting in the endosomal system. SNX18 also contains BAR and SH3 domains. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212830 [Multi-domain] Cd Length: 55 Bit Score: 39.20 E-value: 7.38e-04

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|..
gi 1804876928 1009 ALYSYSSVEPGDLTFIEGEEI-LVTQKDGEWW---TGSIGDRtGIFPSNYVK 1056
Cdd:cd11897      4 ALYDFRSENPGEISLREHEVLsLCSEQDIEGWlegVNSRGDR-GLFPASYVE 54

Src homology 3 domain of Protein arginine N-methyltransferase 2; PRMT2, also called HRMT1L1, belongs to the arginine methyltransferase protein family. It functions as a coactivator to both estrogen receptor alpha (ER-alpha) and androgen receptor (AR), presumably through arginine methylation. The ER-alpha transcription factor is involved in cell proliferation, differentiation, morphogenesis, and apoptosis, and is also implicated in the development and progression of breast cancer. PRMT2 and its variants are upregulated in breast cancer cells and may be involved in modulating the ER-alpha signaling pathway during formation of breast cancer. PRMT2 also plays a role in regulating the function of E2F transcription factors, which are critical cell cycle regulators, by binding to the retinoblastoma gene product (RB). It contains an N-terminal SH3 domain and an AdoMet binding domain. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212740 [Multi-domain] Cd Length: 53 Bit Score: 39.30 E-value: 7.41e-04

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|..
gi 1804876928  785 YKALYRFEARSHDEMSFNSGDIIQVDEKTIGEpgWLYGSFQGNFGWFPCNYV 836
Cdd:cd11806      2 YVAIADFVATDDSQLSFESGDKLLVLRKPSVD--WWWAEHNGCCGYIPASHL 51

Src homology 3 domain of CAS (Crk-Associated Substrate) scaffolding protein family member, Embryonal Fyn-associated Substrate; EFS is also called HEFS, CASS3 (Cas scaffolding protein family member 3) or SIN (Src-interacting protein). It was identified based on interactions with the Src kinases, Fyn and Yes. It plays a role in thymocyte development and acts as a negative regulator of T cell proliferation. CAS proteins function as molecular scaffolds to regulate protein complexes that are involved in many cellular processes. They share a common domain structure that includes an N-terminal SH3 domain, an unstructured substrate domain that contains many YxxP motifs, a serine-rich four-helix bundle, and a FAT-like C-terminal domain. The SH3 domain of CAS proteins binds to diverse partners including FAK, FRNK, Pyk2, PTP-PEST, DOCK180, among others. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212936 Cd Length: 62 Bit Score: 39.49 E-value: 7.57e-04

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....*..
gi 1804876928  924 AQALCSWTAKKDNHLNFSKHDIITVLEQQE----NWWFGEVHGGRGWFPKSYVKIIP 976
Cdd:cd12003      3 AKALYDNAAESPEELSFRRGDVLMVLKREHgslpGWWLCSLHGQQGIAPANRLRLLP 59

First Src Homology 3 domain of FCH and double SH3 domains proteins; This group is composed of FCH and double SH3 domains protein 1 (FCHSD1) and FCHSD2. These proteins have a common domain structure consisting of an N-terminal F-BAR (FES-CIP4 Homology and Bin/Amphiphysin/Rvs), two SH3, and C-terminal proline-rich domains. They have only been characterized in silico and their functions remain unknown. This group also includes the insect protein, nervous wreck, which acts as a regulator of synaptic growth signaling. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212695 [Multi-domain] Cd Length: 57 Bit Score: 39.27 E-value: 7.74e-04

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....
gi 1804876928  786 KALYRFEARSHDEMSFNSGDIIQVDEKTIGEpGWLYG-SFQGNFGWFPCNYVEK 838
Cdd:cd11761      5 KVLYSYEAQRPDELTITEGEELEVIEDGDGD-GWVKArNKSGEVGYVPENYLQF 57

Third Src Homology 3 domain of Nck1 adaptor protein; Nck1 (also called Nckalpha) plays a crucial role in connecting signaling pathways of tyrosine kinase receptors and important effectors in actin dynamics and cytoskeletal remodeling. It binds and activates RasGAP, resulting in the downregulation of Ras. It is also involved in the signaling of endothilin-mediated inhibition of cell migration. Nck adaptor proteins regulate actin cytoskeleton dynamics by linking proline-rich effector molecules to protein tyrosine kinases and phosphorylated signaling intermediates. They contain three SH3 domains and a C-terminal SH2 domain. They function downstream of the PDGFbeta receptor and are involved in Rho GTPase signaling and actin dynamics. Vertebrates contain two Nck adaptor proteins: Nck1 (also called Nckalpha) and Nck2, which show partly overlapping functions but also bind distinct targets. The third SH3 domain of Nck appears to prefer ligands with a PxAPxR motif. SH3 domains are protein interaction domains that usually bind to proline-rich ligands with moderate affinity and selectivity, preferentially a PxxP motif. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212837 [Multi-domain] Cd Length: 57 Bit Score: 39.24 E-value: 8.03e-04

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|..
gi 1804876928  786 KALYRFEARSHDEMSFNSGDIIQVDEKTIGEPGWLY-GSFQGNFGWFPCNYV 836
Cdd:cd11904      4 QALYPFSSSNDEELNFEKGEVMDVIEKPENDPEWWKcRKANGQVGLVPKNYV 55

Src homology 3 domain of Phospholipase C (PLC) gamma 1; PLCgamma1 is widely expressed and is essential in growth and development. It is activated by the TrkA receptor tyrosine kinase and functions as a key regulator of cell differentiation. It is also the predominant PLCgamma in T cells and is required for T cell and NK cell function. PLCs catalyze the hydrolysis of phosphatidylinositol (4,5)-bisphosphate [PtdIns(4,5)P2] to produce Ins(1,4,5)P3 and diacylglycerol (DAG). Ins(1,4,5)P3 initiates the calcium signaling cascade while DAG functions as an activator of PKC. PLCgamma contains a Pleckstrin homology (PH) domain followed by an elongation factor (EF) domain, two catalytic regions of PLC domains that flank two tandem SH2 domains, followed by a SH3 domain and C2 domain. The SH3 domain of PLCgamma1 directly interacts with dynamin-1 and can serve as a guanine nucleotide exchange factor (GEF). It also interacts with Cbl, inhibiting its phosphorylation and activity. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212903 Cd Length: 60 Bit Score: 39.20 E-value: 8.17e-04

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|
gi 1804876928 1009 ALYSYSSVEPGDLTFIEGEEIL-VTQKDGEWWTGSIGDRTGI-FPSNYVK 1056
Cdd:cd11970      8 ALFDYKAQREDELTFTKNAIIQnVEKQEGGWWRGDYGGKKQLwFPSNYVE 57

Src homology 3 domain of the Rho guanine nucleotide exchange factor, ephexin-1 (also called NGEF or ARHGEF27); Ephexin-1, also called NGEF (neuronal GEF) or ARHGEF27, activates RhoA, Tac1, and Cdc42 by exchanging bound GDP for free GTP. It is expressed mainly in the brain in a region associated with movement control. It regulates the stability of postsynaptic acetylcholine receptor (AChR) clusters and thus, plays a critical role in the maturation and neurotransmission of neuromuscular junctions. Ephexin-1 directly interacts with the ephrin receptor EphA4 and their coexpression enhances the ability of ephexin-1 to activate RhoA. It is required for normal axon growth and EphA-induced growth cone collapse. Ephexin-1 contains RhoGEF (also called Dbl-homologous or DH), Pleckstrin Homology (PH), and SH3 domains. The SH3 domains of ARHGEFs play an autoinhibitory role through intramolecular interactions with a proline-rich region N-terminal to the DH domain. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212872 [Multi-domain] Cd Length: 55 Bit Score: 39.16 E-value: 8.25e-04

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....*
gi 1804876928 1080 QVTSAYVASGSEQLSLAPGQLILILKKNSSGWWQGElqaRGKKRQKGWFPASHVK 1134
Cdd:cd11939      3 QCVHPYVSQEPDELSLELADVLNILDKTDDGWIFGE---RLHDQERGWFPSSVVE 54

MAEBL; Provisional

Pssm-ID: 173412 [Multi-domain] Cd Length: 2084 Bit Score: 44.36 E-value: 8.39e-04

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1804876928  384 QKIQEEEPQKKLPVTFEDKRKANYERGN-----VELEKRRQALMEQQQREAERKAQK-EKEEWERKQREL----QEQEWK 453
Cdd:PTZ00121  1568 EAKKAEEDKNMALRKAEEAKKAEEARIEevmklYEEEKKMKAEEAKKAEEAKIKAEElKKAEEEKKKVEQlkkkEAEEKK 1647

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1804876928  454 KQLELEKRLE----KQRELERQREEErrkeierreaaKQELERQRRLEWERIRRQEllnQRNREQEEivrlnsKKKSlhl 529
Cdd:PTZ00121  1648 KAEELKKAEEenkiKAAEEAKKAEED-----------KKKAEEAKKAEEDEKKAAE---ALKKEAEE------AKKA--- 1704

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1804876928  530 elEALNGKHQQISGRLQDVRLRKQTQKTEIEVLDKQCDLEIMEIKQLQQElQDYQNKLIYLVPEKQLLNERIKNmqlgnt 609
Cdd:PTZ00121  1705 --EELKKKEAEEKKKAEELKKAEEENKIKAEEAKKEAEEDKKKAEEAKKD-EEEKKKIAHLKKEEEKKAEEIRK------ 1775

                          250       260       270       280       290       300       310       320
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1804876928  610 pdlgidllHKKSLEKEELCQRLKEQLDALEKETASKlseMDSFNNQLKCGNMDDSVLQCLLSLLSCLnnlfllLKELRES 689
Cdd:PTZ00121  1776 --------EKEAVIEEELDEEDEKRRMEVDKKIKDI---FDNFANIIEGGKEGNLVINDSKEMEDSA------IKEVADS 1838

                          330       340       350       360       370       380       390       400
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1804876928  690 YNTQQ---LALEQLHKIKRDKLKEIERKRSELIQKKKLEDEAIRKAKQGKENlwrESLRKEEEEKQ------KRLQEEKT 760
Cdd:PTZ00121  1839 KNMQLeeaDAFEKHKFNKNNENGEDGNKEADFNKEKDLKEDDEEEIEEADEI---EKIDKDDIEREipnnnmAGKNNDII 1915

                          410       420
                   ....*....|....*....|
gi 1804876928  761 QEKVQEEE---RKVEEKQCE 777
Cdd:PTZ00121  1916 DDKLDKDEyikRDAEETREE 1935

First Src Homology 3 domain of Bud emergence protein 1 and similar domains; Members of this subfamily bear similarity to Saccharomyces cerevisiae Bem1p, containing two Src Homology 3 (SH3) domains at the N-terminus, a central PX domain, and a C-terminal PB1 domain. Bem1p is a scaffolding protein that is critical for proper Cdc42p activation during bud formation in yeast. During budding and mating, Bem1p migrates to the plasma membrane where it can serve as an adaptor for Cdc42p and some other proteins. Bem1p also functions as an effector of the G1 cyclin Cln3p and the cyclin-dependent kinase Cdc28p in promoting vacuolar fusion. SH3 domains bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs; they play a role in the regulation of enzymes by intramolecular interactions, changing the subcellular localization of signal pathway components and mediate multiprotein complex assemblies.

Pssm-ID: 212811 [Multi-domain] Cd Length: 54 Bit Score: 38.81 E-value: 8.66e-04

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|...
gi 1804876928 1153 VI-AMYDYVANNEDELNFSKGQLINVLNKDDPD-WWQGE--INGVTGLFPSNY 1201
Cdd:cd11878      1 VIrALYDYRAQTPGELSFSKGDFFHVIGEEDQGeWYEATnpVTGKRGLVPKSY 53

Src homology 3 domain of CAS (Crk-Associated Substrate) scaffolding proteins; CAS proteins function as molecular scaffolds to regulate protein complexes that are involved in many cellular processes including migration, chemotaxis, apoptosis, differentiation, and progenitor cell function. They mediate the signaling of integrins at focal adhesions where they localize, and thus, regulate cell invasion and survival. Over-expression of these proteins is implicated in poor prognosis, increased metastasis, and resistance to chemotherapeutics in many cancers such as breast, lung, melanoma, and glioblastoma. CAS proteins have also been linked to the pathogenesis of inflammatory disorders, Alzheimer's, Parkinson's, and developmental defects. They share a common domain structure that includes an N-terminal SH3 domain, an unstructured substrate domain that contains many YxxP motifs, a serine-rich four-helix bundle, and a FAT-like C-terminal domain. Vertebrates contain four CAS proteins: BCAR1 (or p130Cas), NEDD9 (or HEF1), EFS (or SIN), and CASS4 (or HEPL). The SH3 domain of CAS proteins binds to diverse partners including FAK, FRNK, Pyk2, PTP-PEST, DOCK180, among others. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212778 Cd Length: 56 Bit Score: 38.87 E-value: 8.67e-04

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....*
gi 1804876928  924 AQALCSWTAKKDNHLNFSKHDIITVLEQQ----ENWWFGEVHGGRGWFPKSYVKI 974
Cdd:cd11844      2 ARALYDNVAESPDELAFRRGDILTVLEQNtaglEGWWLCSLRGRQGIAPGNRLKL 56

Src Homology 3 domain of Apoptosis Stimulating of p53 protein 1; ASPP1, like ASPP2, activates the apoptotic function of the p53 family of tumor suppressors (p53, p63, and p73). In addition, it functions in the cytoplasm to regulate the nuclear localization of the transcriptional cofactors YAP and TAZ by inihibiting their phosphorylation; YAP and TAZ are important regulators of cell expansion, differentiation, migration, and invasion. ASPP1 is downregulated in breast tumors expressing wild-type p53. It contains a proline-rich region, four ankyrin (ANK) repeats, and an SH3 domain at its C-terminal half. The SH3 domain and the ANK repeats of ASPP1 contribute to the p53 binding site; they bind to the DNA binding domain of p53. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212887 [Multi-domain] Cd Length: 57 Bit Score: 39.23 E-value: 8.74e-04

                           10        20        30        40
                   ....*....|....*....|....*....|....*....|....*....
gi 1804876928 1009 ALYSYSSVEPGDLTFIEGEEI-LVTQKDG---EWWTGSIGDRTGIFPSN 1053
Cdd:cd11954      5 ALWDYEAQNADELSFQEGDAItILRRKDDsetEWWWARLNDKEGYVPKN 53

Src homology 3 domain of Type I fungal Myosins; Type I myosins (myosin-I) are actin-dependent motors in endocytic actin structures and actin patches. They play roles in membrane traffic in endocytic and secretory pathways, cell motility, and mechanosensing. Saccharomyces cerevisiae has two myosins-I, Myo3 and Myo5, which are involved in endocytosis and the polarization of the actin cytoskeleton. Myosin-I contains an N-terminal actin-activated ATPase, a phospholipid-binding TH1 (tail homology 1) domain, and a C-terminal extension which includes an F-actin-binding TH2 domain, an SH3 domain, and an acidic peptide that participates in activating the Arp2/3complex. The SH3 domain of myosin-I is required for myosin-I-induced actin polymerization. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212792 [Multi-domain] Cd Length: 55 Bit Score: 38.91 E-value: 9.26e-04

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....
gi 1804876928 1007 YIALYSYSSVEPGDLTFIEGEEILVTQK-DGEWWTGSIGDRT--GIFPSNYVKP 1057
Cdd:cd11858      2 YKALYDFAGSVANELSLKKDDIVYIVQKeDNGWWLAKKLDESkeGWVPAAYLEE 55

Uncharacterized conserved protein YhaN, contains AAA domain [Function unknown];

Pssm-ID: 443752 [Multi-domain] Cd Length: 641 Bit Score: 43.99 E-value: 9.32e-04

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1804876928  549 RLRKQTQKTEIEVLDKQCDLEImEIKQLQQELQDYQNkliyLVPEKQLLNERIKNMQLGNTpDLGIDLlhkKSLEKEELC 628
Cdd:COG4717     57 ELFKPQGRKPELNLKELKELEE-ELKEAEEKEEEYAE----LQEELEELEEELEELEAELE-ELREEL---EKLEKLLQL 127

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1804876928  629 QRLKEQLDALEKETASKLSEMDSFNNQLKcgnmddsvlqcllsllsclnnlflLLKELRESYNTQQLALEQLHK------ 702
Cdd:COG4717    128 LPLYQELEALEAELAELPERLEELEERLE------------------------ELRELEEELEELEAELAELQEeleell 183

                          170       180       190       200       210       220       230
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|..
gi 1804876928  703 -----IKRDKLKEIERKRSELIQKKKLEDEAIRKAKQgkenlWRESLRKEEEEKQKRLQEEKTQEKVQEEER 769
Cdd:COG4717    184 eqlslATEEELQDLAEELEELQQRLAELEEELEEAQE-----ELEELEEELEQLENELEAAALEERLKEARL 250

Third Src homology 3 domain (or SH3C) of Intersectin-2; Intersectin-2 (ITSN2) is an adaptor protein that functions in exo- and endocytosis, actin cytoskeletal reorganization, and signal transduction. It plays a role in clathrin-coated pit (CCP) formation. It binds to many proteins through its multidomain structure and facilitate the assembly of multimeric complexes. ITSN2 also functions as a specific GEF for Cdc42 activation in epithelial morphogenesis, and is required in mitotic spindle orientation. It exists in alternatively spliced short and long isoforms. The short isoform contains two Eps15 homology domains (EH1 and EH2), a coiled-coil region and five SH3 domains (SH3A-E), while the long isoform, in addition, contains RhoGEF (also called Dbl-homologous or DH), Pleckstrin homology (PH) and C2 domains. The third SH3 domain (SH3C) of ITSN2 has been shown to bind the K15 protein of Kaposi's sarcoma-associated herpesvirus. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212925 Cd Length: 52 Bit Score: 38.84 E-value: 9.71e-04

                           10        20        30        40
                   ....*....|....*....|....*....|....*....|....*...
gi 1804876928  926 ALCSWTAKKDNHLNFSKHDIITVLEQQENWWFGEVHGGRGWFPKSYVK 973
Cdd:cd11992      4 ALYPYSSSEPGDLTFNEGEEILVTQKDGEWWTGSIEDRTGIFPSNYVR 51

Chromatin assembly factor 1 complex p150 subunit, N-terminal; CAF-1_p150 is a polypeptide subunit of CAF-1, which functions in depositing newly synthesized and acetylated histones H3/H4 into chromatin during DNA replication and repair. CAF-1_p150 includes the HP1 interaction site, the PEST, KER and ED interacting sites. CAF-1_p150 interacts directly with newly synthesized and acetylated histones through the acidic KER and ED domains. The PEST domain is associated with proteins that undergo rapid proteolysis.

Pssm-ID: 402959 [Multi-domain] Cd Length: 164 Bit Score: 41.60 E-value: 9.84e-04

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1804876928  685 ELRESYNTQQLALEQLHKIKRDKLKEIERKRSELIQKKKlEDEAIRKAKQGKENlwRESLRKEEEEKQkRLQEEKTQEKV 764
Cdd:pfam11600   22 KERLRRQLKLEAEKEEKERLKEEAKAEKERAKEEARRKK-EEEKELKEKERREK--KEKDEKEKAEKL-RLKEEKRKEKQ 97

                           90
                   ....*....|.
gi 1804876928  765 QEEERKVEEKQ 775
Cdd:pfam11600   98 EALEAKLEEKR 108

Src homology 3 domain of Rho GTPase-activating proteins 32 and 33, and similar proteins; Members of this family contain N-terminal PX and Src Homology 3 (SH3) domains, a central Rho GAP domain, and C-terminal extensions. RhoGAPs (or ARHGAPs) bind to Rho proteins and enhance the hydrolysis rates of bound GTP. ARHGAP32 is also called RICS, PX-RICS, p250GAP, or p200RhoGAP. It is a Rho GTPase-activating protein for Cdc42 and Rac1, and is implicated in the regulation of postsynaptic signaling and neurite outgrowth. PX-RICS, a variant of RICS that contain PX and SH3 domains, is the main isoform expressed during neural development. It is involved in neural functions including axon and dendrite extension, postnatal remodeling, and fine-tuning of neural circuits during early brain development. ARHGAP33, also called sorting nexin 26 or TCGAP (Tc10/CDC42 GTPase-activating protein), is widely expressed in the brain where it is involved in regulating the outgrowth of axons and dendrites and is regulated by the protein tyrosine kinase Fyn. It is translocated to the plasma membrane in adipocytes in response to insulin and may be involved in the regulation of insulin-stimulated glucose transport. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212769 [Multi-domain] Cd Length: 54 Bit Score: 38.97 E-value: 9.90e-04

                           10        20        30        40
                   ....*....|....*....|....*....|....*....|....*..
gi 1804876928 1159 YVANNEDELNFSKGQLINVLN---KDDPDWWQGEINGVTGLFPSNYV 1202
Cdd:cd11835      8 YTAQAPDELSLEVGDIVSVIDmppPEESTWWRGKKGFQVGFFPSECV 54

Second C-terminal Src homology 3 domain of Dynamin Binding Protein, also called Tuba, and similar domains; DNMBP or Tuba is a cdc42-specific guanine nucleotide exchange factor (GEF) that contains four N-terminal SH3 domains, a central RhoGEF [or Dbl homology (DH)] domain followed by a Bin/Amphiphysin/Rvs (BAR) domain, and two C-terminal SH3 domains. It provides a functional link between dynamin, Rho GTPase signaling, and actin dynamics. It plays an important role in regulating cell junction configuration. The C-terminal SH3 domains of DNMBP bind to N-WASP and Ena/VASP proteins, which are key regulatory proteins of the actin cytoskeleton. Also included in this subfamily is the second C-terminal SH3 domain of Rho guanine nucleotide exchange factor 37 (ARHGEF37), whose function is still unknown. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212734 [Multi-domain] Cd Length: 57 Bit Score: 38.89 E-value: 9.94e-04

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....*.
gi 1804876928 1007 YIALYSYSSVEPGDLTFIEGEEILVTQK-----DGEWWTGSIGDRTGIFPSNYVKP 1057
Cdd:cd11800      2 YYALYTFEARSPGELSVTEGQVVTVLEKhdlkgNPEWWLVEDRGKQGYVPSNYLAK 57

MAP7 (E-MAP-115) family; The organization of microtubules varies with the cell type and is presumably controlled by tissue-specific microtubule-associated proteins (MAPs). The 115-kDa epithelial MAP (E-MAP-115/MAP7) has been identified as a microtubule-stabilising protein predominantly expressed in cell lines of epithelial origin. The binding of this microtubule associated protein is nucleotide independent.

Pssm-ID: 461709 [Multi-domain] Cd Length: 153 Bit Score: 41.56 E-value: 1.00e-03

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1804876928  387 QEEEPQKKLPvtfEDKRKANYERGNVELEKRRQAlMEQQQREAERKAQKEKEEWERKQRELQEQEwkkqlelekRLEKqr 466
Cdd:pfam05672   37 KEEEERLRKE---ELRRRAEEERARREEEARRLE-EERRREEEERQRKAEEEAEEREQREQEEQE---------RLQK-- 101

                           90       100       110       120       130       140
                   ....*....|....*....|....*....|....*....|....*....|....*....|
gi 1804876928  467 elerQreeerrkeierreaaKQELERQRRLEWERIRR-QELLNQRNrEQEeivRLNSKKK 525
Cdd:pfam05672  102 ----Q---------------KEEAEAKAREEAERQRQeREKIMQQE-EQE---RLERKKR 138

Src Homology 3 domain of Myosin XVb; Myosin XVb, also called KIAA1783, was named based on its similarity with myosin XVa. It is a transcribed and unprocessed pseudogene whose predicted amino acid sequence contains mutated or deleted amino acid residues that are normally conserved and important for myosin function. The related myosin XVa is important for normal growth of mechanosensory stereocilia of inner ear hair cells. Myosin XVa contains a unique N-terminal extension followed by a motor domain, light chain-binding IQ motifs, and a tail consisting of a pair of MyTH4-FERM tandems separated by a SH3 domain, and a PDZ domain. SH3 domains bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs; they play a role in the regulation of enzymes by intramolecular interactions, changing the subcellular localization of signal pathway components and mediate multiprotein complex assemblies.

Pssm-ID: 213001 Cd Length: 55 Bit Score: 38.70 E-value: 1.02e-03

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|.
gi 1804876928  787 ALYRFEARSHDEMSFNSGDIIQVDEKTIGEPGWLYGSFQGNFGWFPCNYVE 837
Cdd:cd12068      4 ALRSYITDDKSLLSFHRGDLIKLLPMAGLEPGWQFGSTGGRSGLFPADIVQ 54

Septal ring factor EnvC, activator of murein hydrolases AmiA and AmiB [Cell cycle control, cell division, chromosome partitioning];

Pssm-ID: 443969 [Multi-domain] Cd Length: 377 Bit Score: 43.60 E-value: 1.07e-03

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1804876928  423 EQQQREAERKA-QKEKEEWERKQRELQEQEWKKQLELEKrLEKQRELERQREEERRKEIERREAAKQELERQR-RLEWER 500
Cdd:COG4942     21 AAAEAEAELEQlQQEIAELEKELAALKKEEKALLKQLAA-LERRIAALARRIRALEQELAALEAELAELEKEIaELRAEL 99

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1804876928  501 IRRQELLNQRNREQEEIVRLNSKKKSLH----LELEALNGKHQQISGRLQDVRLRKQTQKTEIEVLDKQCDLEIMEIKQL 576
Cdd:COG4942    100 EAQKEELAELLRALYRLGRQPPLALLLSpedfLDAVRRLQYLKYLAPARREQAEELRADLAELAALRAELEAERAELEAL 179

                          170       180       190       200       210       220       230
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 1804876928  577 QQELQDYQNKLIYLVPEKQLLNERIKNMqlgntpdlgIDLLHKKSLEKEELCQRLKEQLDALEKETASKLSEMDS 651
Cdd:COG4942    180 LAELEEERAALEALKAERQKLLARLEKE---------LAELAAELAELQQEAEELEALIARLEAEAAAAAERTPA 245

Second Src homology 3 domain of Tyrosine kinase substrate with five SH3 domains; Tks5, also called SH3 and PX domain-containing protein 2A (SH3PXD2A) or Five SH (FISH), is a scaffolding protein and Src substrate that is localized in podosomes, which are electron-dense structures found in Src-transformed fibroblasts, osteoclasts, macrophages, and some invasive cancer cells. It binds and regulates some members of the ADAMs family of transmembrane metalloproteases, which function as sheddases and mediators of cell and matrix interactions. It is required for podosome formation, degradation of the extracellular matrix, and cancer cell invasion. Tks5 contains an N-terminal Phox homology (PX) domain and five SH3 domains. This model characterizes the second SH3 domain of Tks5. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 213010 Cd Length: 54 Bit Score: 38.86 E-value: 1.09e-03

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|
gi 1804876928 1154 IAMYDYVANNEDELNFSKGQLINVLNKDDPDWWQGEINGVTGLFPSNYVK 1203
Cdd:cd12077      4 VTVQPYTSQGKDEIGFEKGVTVEVIQKNLEGWWYIRYLGKEGWAPASYLK 53

Uncharacterized coiled-coil protein, contains DUF342 domain [Function unknown];

Pssm-ID: 440951 [Multi-domain] Cd Length: 297 Bit Score: 42.98 E-value: 1.11e-03

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1804876928  413 ELEKRRQALMEQQQ--REAERKAQKEKEEWERKQRELQEQewKKQLelekrlekqrelerqreeerrkeierreaaKQEL 490
Cdd:COG1340     12 ELEEKIEELREEIEelKEKRDELNEELKELAEKRDELNAQ--VKEL------------------------------REEA 59

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1804876928  491 ERQRRleweriRRQELLNQRNREQEEIVRLNSKKKSLHLELEALNGKHQQISGRLQDV-RLRKQTQKTE----IEVLDKQ 565
Cdd:COG1340     60 QELRE------KRDELNEKVKELKEERDELNEKLNELREELDELRKELAELNKAGGSIdKLRKEIERLEwrqqTEVLSPE 133

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1804876928  566 CDLEIME-IKQLQQELQ------DYQNKLIYLvpEKQLLNERIKNMQLgntpdlgidllHKKSLEKEELCQRLKEQLDAL 638
Cdd:COG1340    134 EEKELVEkIKELEKELEkakkalEKNEKLKEL--RAELKELRKEAEEI-----------HKKIKELAEEAQELHEEMIEL 200

                          250       260       270       280       290       300       310       320
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1804876928  639 eKETASKLS-EMDSFNNQlkcgnmddsvlqcllsllsclnnlFLLLKELRESYNTQQLAL-EQLHKIkRDKLKEIeRKRS 716
Cdd:COG1340    201 -YKEADELRkEADELHKE------------------------IVEAQEKADELHEEIIELqKELREL-RKELKKL-RKKQ 253

                          330       340
                   ....*....|....*....|...
gi 1804876928  717 ELIQKKKLEDEAIRKAKQGKENL 739
Cdd:COG1340    254 RALKREKEKEELEEKAEEIFEKL 276

Third (or C-terminal) Src Homology 3 domain of Sorbin and SH3 domain containing 1 (Sorbs1), also called ponsin; Sorbs1 is also called ponsin, SH3P12, or CAP (c-Cbl associated protein). It is an adaptor protein containing one sorbin homology (SoHo) and three SH3 domains. It binds Cbl and plays a major role in regulating the insulin signaling pathway by enhancing insulin-induced phosphorylation of Cbl. Sorbs1, like vinexin, localizes at cell-ECM and cell-cell adhesion sites where it binds vinculin, paxillin, and afadin. It may function in the control of cell motility. Other interaction partners of Sorbs1 include c-Abl, Sos, flotillin, Grb4, ataxin-7, filamin C, among others. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212849 [Multi-domain] Cd Length: 59 Bit Score: 38.82 E-value: 1.12e-03

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....
gi 1804876928  925 QALCSWTAKKDNHLNFSKHDIITVLEQQENWWF-GEVHGGR--GWFPKSYVKII 975
Cdd:cd11916      5 QALYSYAPQNDDELELRDGDIVDVMEKCDDGWFvGTSRRTKqfGTFPGNYVKLL 58

Src Homology 3 domain of Src Kinase-Associated Phosphoprotein 2; SKAP2, also called SKAP55-Related (SKAP55R) or SKAP55 homolog (SKAP-HOM or SKAP55-HOM), is an immune cell-specific adaptor protein that plays an important role in adhesion and migration of B-cells and macrophages. Binding partners include ADAP (adhesion and degranulation-promoting adaptor protein), YopH, SHPS1, and HPK1. SKAP2 has also been identified as a substrate for lymphoid-specific tyrosine phosphatase (Lyp), which has been implicated in a wide variety of autoimmune diseases. It contains a pleckstrin homology (PH) domain, a C-terminal SH3 domain, and several tyrosine phosphorylation sites. Like SKAP1, SKAP2 is expected to bind primarily to a proline-rich region of ADAP through its SH3 domain; its degradation may be regulated by ADAP. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212978 Cd Length: 53 Bit Score: 38.73 E-value: 1.13e-03

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|.
gi 1804876928  925 QALCSWTAKKDNHLNFSKHDIITVLEQQEN---WWFGEVHGGRGWFPKSYV 972
Cdd:cd12045      3 QGLWDCTGDQPDELSFKRGDTIYILSKEYNrfgWWVGEMKGTIGLVPKAYI 53

C-terminal Src Homology 3 domain of the p67phox subunit of NADPH oxidase and similar proteins; This subfamily is composed of p67phox, NADPH oxidase activator 1 (Noxa1), and similar proteins. p67phox, also called Neutrophil cytosol factor 2 (NCF-2), and Noxa1 are homologs and are the cytosolic subunits of the phagocytic (Nox2) and nonphagocytic (Nox1) NADPH oxidase complexes, respectively. NADPH oxidase catalyzes the transfer of electrons from NADPH to oxygen during phagocytosis forming superoxide and reactive oxygen species. p67phox and Noxa1 play regulatory roles. p67phox contains N-terminal TPR, first SH3 (or N-terminal or central SH3), PB1, and C-terminal SH3 domains. Noxa1 has a similar domain architecture except it is lacking the N-terminal SH3 domain. The TPR domain of both binds activated GTP-bound Rac, while the C-terminal SH3 domain of p67phox and Noxa1 binds the polyproline motif found at the C-terminus of p47phox and Noxo1, respectively. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212803 [Multi-domain] Cd Length: 53 Bit Score: 38.66 E-value: 1.16e-03

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|..
gi 1804876928  923 KAQALCSWTAKKDNHLNFSKHDIITVLEQ-QENWWFGEVHGGRGWFPKSYVK 973
Cdd:cd11870      1 QVVALHRYEAQGPEDLGFREGDTIDVLSEvNEAWLEGHSDGRVGIFPKCFVV 52

RNase Y N-terminal region;

Pssm-ID: 463456 [Multi-domain] Cd Length: 201 Bit Score: 42.18 E-value: 1.16e-03

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1804876928  696 ALEQLHKIKRDKLKEIERKRSELiqkKKLEDEAIRKakqgKENLWR--ESLRKEEEEKQKRLQE-EKTQEKVQEEERKVE 772
Cdd:pfam12072   58 AKEEIHKLRAEAERELKERRNEL---QRQERRLLQK----EETLDRkdESLEKKEESLEKKEKElEAQQQQLEEKEEELE 130

                           90       100
                   ....*....|....*....|...
gi 1804876928  773 EKQCEPASALVNYKALYRFEARS 795
Cdd:pfam12072  131 ELIEEQRQELERISGLTSEEAKE 153

Src homology 3 domain of APC-Stimulated guanine nucleotide Exchange Factor 2; ASEF2, also called Spermatogenesis-associated protein 13 (SPATA13), is a GEF that localizes with actin at the leading edge of cells and is important in cell migration and adhesion dynamics. GEFs activate small GTPases by exchanging bound GDP for free GTP. ASEF2 can activate both Rac 1 and Cdc42, but only Rac1 activation is necessary for increased cell migration and adhesion turnover. Together with APC (adenomatous polyposis coli) and Neurabin2, a scaffold protein that binds F-actin, it is involved in regulating HGF-induced cell migration. ASEF2 contains a SH3 domain followed by RhoGEF (also called Dbl-homologous or DH) and Pleckstrin Homology (PH) domains. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212907 Cd Length: 54 Bit Score: 38.51 E-value: 1.16e-03

                           10        20        30        40
                   ....*....|....*....|....*....|....*....|....*....
gi 1804876928 1009 ALYSYSSVEPGDLTFIEGEEILVTQ-KDGEWWTGSIGDRTGIFPSNYVK 1056
Cdd:cd11974      5 ALWDHVTMDDQELAFKAGDVIRVLEaSNKDWWWGRNEDREAWFPASFVR 53

Fourth Src homology 3 domain of ADAM-binding protein Eve-1; Eve-1, also called SH3 domain-containing protein 19 (SH3D19) or EEN-binding protein (EBP), exists in multiple alternatively spliced isoforms. The longest isoform contains five SH3 domain in the C-terminal region and seven proline-rich motifs in the N-terminal region. It is abundantly expressed in skeletal muscle and heart, and may be involved in regulating the activity of ADAMs (A disintegrin and metalloproteases). Eve-1 interacts with EEN, an endophilin involved in endocytosis and may be the target of the MLL-EEN fusion protein that is implicated in leukemogenesis. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212751 [Multi-domain] Cd Length: 50 Bit Score: 38.61 E-value: 1.18e-03

                           10        20        30        40
                   ....*....|....*....|....*....|....*....|....*....
gi 1804876928  924 AQALCSWTAKKDNHLNFSKHDIITVLEQQE-NWWFGEVHGGRGWFPKSY 971
Cdd:cd11817      2 AVALYDFTGETEEDLSFQRGDRILVTEHLDaEWSRGRLNGREGIFPRAF 50

Src homology 3 domain of CAS (Crk-Associated Substrate) scaffolding protein family member 4; CASS4, also called HEPL (HEF1-EFS-p130Cas-like), localizes to focal adhesions and plays a role in regulating FAK activity, focal adhesion integrity, and cell spreading. It is most abundant in blood cells and lung tissue, and is also found in high levels in leukemia and ovarian cell lines. CAS proteins function as molecular scaffolds to regulate protein complexes that are involved in many cellular processes. They share a common domain structure that includes an N-terminal SH3 domain, an unstructured substrate domain that contains many YxxP motifs, a serine-rich four-helix bundle, and a FAT-like C-terminal domain. The SH3 domain of CAS proteins binds to diverse partners including FAK, FRNK, Pyk2, PTP-PEST, DOCK180, among others. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212933 Cd Length: 57 Bit Score: 38.71 E-value: 1.20e-03

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....*..
gi 1804876928  922 LKAQALCSWTAKKDNHLNFSKHDIITVLEQQ----ENWWFGEVHGGRGWFPKSYVKI 974
Cdd:cd12000      1 LLARALYDNKADCSDELAFRRGDILTVLEQNvpgsEGWWKCLLHGRQGLAPANRLQL 57

Src homology 3 domain of Protein arginine N-methyltransferase 2; PRMT2, also called HRMT1L1, belongs to the arginine methyltransferase protein family. It functions as a coactivator to both estrogen receptor alpha (ER-alpha) and androgen receptor (AR), presumably through arginine methylation. The ER-alpha transcription factor is involved in cell proliferation, differentiation, morphogenesis, and apoptosis, and is also implicated in the development and progression of breast cancer. PRMT2 and its variants are upregulated in breast cancer cells and may be involved in modulating the ER-alpha signaling pathway during formation of breast cancer. PRMT2 also plays a role in regulating the function of E2F transcription factors, which are critical cell cycle regulators, by binding to the retinoblastoma gene product (RB). It contains an N-terminal SH3 domain and an AdoMet binding domain. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212740 [Multi-domain] Cd Length: 53 Bit Score: 38.53 E-value: 1.21e-03

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|...
gi 1804876928 1006 EYIALYSYSSVEPGDLTFIEGEEILVTQKDG-EWWTGSIGDRTGIFPSNYVKP 1057
Cdd:cd11806      1 EYVAIADFVATDDSQLSFESGDKLLVLRKPSvDWWWAEHNGCCGYIPASHLHQ 53

Src Homology 3 domain of Myosin XVb; Myosin XVb, also called KIAA1783, was named based on its similarity with myosin XVa. It is a transcribed and unprocessed pseudogene whose predicted amino acid sequence contains mutated or deleted amino acid residues that are normally conserved and important for myosin function. The related myosin XVa is important for normal growth of mechanosensory stereocilia of inner ear hair cells. Myosin XVa contains a unique N-terminal extension followed by a motor domain, light chain-binding IQ motifs, and a tail consisting of a pair of MyTH4-FERM tandems separated by a SH3 domain, and a PDZ domain. SH3 domains bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs; they play a role in the regulation of enzymes by intramolecular interactions, changing the subcellular localization of signal pathway components and mediate multiprotein complex assemblies.

Pssm-ID: 213001 Cd Length: 55 Bit Score: 38.70 E-value: 1.23e-03

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|...
gi 1804876928 1153 VIAMYDYVANNEDELNFSKGQLINVLNKD--DPDWWQGEINGVTGLFPSNYVK 1203
Cdd:cd12068      2 VVALRSYITDDKSLLSFHRGDLIKLLPMAglEPGWQFGSTGGRSGLFPADIVQ 54

Src homology 3 domain of the Rho guanine nucleotide exchange factors ARHGEF5 and ARHGEF19; ARHGEF5, also called ephexin-3 or TIM (Transforming immortalized mammary oncogene), is a potent activator of RhoA and it plays roles in regulating cell shape, adhesion, and migration. It binds to the SH3 domain of Src and is involved in regulating Src-induced podosome formation. ARHGEF19, also called ephexin-2 or WGEF (weak-similarity GEF), is highly expressed in the intestine, liver, heart and kidney. It activates RhoA, Cdc42, and Rac 1, and has been shown to activate RhoA in the Wnt-PCP (planar cell polarity) pathway. It is involved in the regulation of cell polarity and cytoskeletal reorganization. ARHGEF5 and ARHGEF19 contain RhoGEF (also called Dbl-homologous or DH), Pleckstrin Homology (PH), and SH3 domains. The SH3 domains of ARHGEFs play an autoinhibitory role through intramolecular interactions with a proline-rich region N-terminal to the DH domain. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212873 Cd Length: 55 Bit Score: 38.62 E-value: 1.24e-03

                           10        20        30        40
                   ....*....|....*....|....*....|....*....|....*....
gi 1804876928  791 FEARSHDEMSFNSGDIIQVdeKTIGEPGWLYGS--FQGNFGWFPCNYVE 837
Cdd:cd11940      8 YKAQENDELTLEKADIIMV--RQQSSDGWLEGVrlSDGERGWFPQSHVE 54

Domain of unknown function (DUF4670); This family of proteins is found in eukaryotes. Proteins in this family are typically between 373 and 763 amino acids in length.

Pssm-ID: 464815 [Multi-domain] Cd Length: 522 Bit Score: 43.40 E-value: 1.25e-03

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1804876928  684 KELRESYNTQQLALEQLHKIkRDKLKEIERKRSELIQ--KKKLEDEAIRKAKQGK-----ENLWRESLRKEEEEKQKRLQ 756
Cdd:pfam15709  355 REQEEQRRLQQEQLERAEKM-REELELEQQRRFEEIRlrKQRLEEERQRQEEEERkqrlqLQAAQERARQQQEEFRRKLQ 433

                           90
                   ....*....|....*....
gi 1804876928  757 EEKTQEKVQEEERKVEEKQ 775
Cdd:pfam15709  434 ELQRKKQQEEAERAEAEKQ 452

Exopolysaccharide export protein/domain GumC/Wzc1 [Cell wall/membrane/envelope biogenesis];

Pssm-ID: 442439 [Multi-domain] Cd Length: 687 Bit Score: 43.47 E-value: 1.25e-03

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1804876928  546 QDVRLRKQTQKTEIEVLDKQcdleimeIKQLQQELQDYQNKLiylvpekQLLNERIKNMQLGNTPDLGIDLLhkksleke 625
Cdd:COG3206    164 QNLELRREEARKALEFLEEQ-------LPELRKELEEAEAAL-------EEFRQKNGLVDLSEEAKLLLQQL-------- 221

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1804876928  626 elcQRLKEQLDALEKETASKLSEMDSFNNQLKCGNMDDSVLQCLLsllsclnnlflLLKELRESYNTQQLALEQL----- 700
Cdd:COG3206    222 ---SELESQLAEARAELAEAEARLAALRAQLGSGPDALPELLQSP-----------VIQQLRAQLAELEAELAELsaryt 287

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1804876928  701 --H-KIK--RDKLKEIERKRSELIQKKKLEDEAIRKAKQGKEnlwrESLRKEEEEKQKRLQEEKTQEKVQEE-ERKVEEK 774
Cdd:COG3206    288 pnHpDVIalRAQIAALRAQLQQEAQRILASLEAELEALQARE----ASLQAQLAQLEARLAELPELEAELRRlEREVEVA 363


                   .
gi 1804876928  775 Q 775
Cdd:COG3206    364 R 364

Src Homology 3 domain of Sorting Nexin 9 and similar proteins; Sorting nexins (SNXs) are Phox homology (PX) domain containing proteins that are involved in regulating membrane traffic and protein sorting in the endosomal system. SNXs differ from each other in their lipid-binding specificity, subcellular localization and specific function in the endocytic pathway. This subfamily consists of SH3 domain containing SNXs including SNX9, SNX18, SNX33, and similar proteins. SNX9 is localized to plasma membrane endocytic sites and acts primarily in clathrin-mediated endocytosis, while SNX18 is localized to peripheral endosomal structures, and acts in a trafficking pathway that is clathrin-independent but relies on AP-1 and PACS1. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212697 [Multi-domain] Cd Length: 55 Bit Score: 38.46 E-value: 1.26e-03

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|
gi 1804876928 1085 YVASGSEQLSLAPGQLILILKKNS-SGWWQGElQARGKkrqKGWFPASHV 1133
Cdd:cd11763      8 FDSQPSGELSLRAGEVLTITRQDVgDGWLEGR-NSRGE---VGLFPSSYV 53

Src Homology 3 domain of Saccharomyces cerevisiae Nap1-binding protein 2 and similar fungal proteins; This subfamily includes Saccharomyces cerevisiae Nbp2 (Nucleosome assembly protein 1 (Nap1)-binding protein 2), Schizosaccharomyces pombe Skb5, and similar proteins. Nbp2 interacts with Nap1, which is essential for maintaining proper nucleosome structures in transcription and replication. It is also the binding partner of the yeast type II protein phosphatase Ptc1p and serves as a scaffolding protein that brings seven kinases in close contact to Ptc1p. Nbp2 plays a role many cell processes including organelle inheritance, mating hormone response, cell wall stress, mitotic cell growth at elevated temperatures, and high osmolarity. Skb5 interacts with the p21-activated kinase (PAK) homolog Shk1, which is critical for fission yeast cell viability. Skb5 activates Shk1 and plays a role in regulating cell morphology and growth under hypertonic conditions. Nbp2 and Skb5 contain an SH3 domain. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212799 Cd Length: 55 Bit Score: 38.65 E-value: 1.27e-03

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....*
gi 1804876928 1152 QVIAMYDYVANNEDELNFSKGQLINVLNKDDPDWW--QGEINGVTGLFPSNYVKM 1204
Cdd:cd11865      1 RAVALYDFEPEHDNELGFAEGQILFILYKHGQGWLiaEDESGGKTGLVPEEFVSY 55

Second Src homology 3 domain of Tyrosine kinase substrate with four SH3 domains; Tks4, also called SH3 and PX domain-containing protein 2B (SH3PXD2B) or HOFI, is a Src substrate and scaffolding protein that plays an important role in the formation of podosomes and invadopodia, the dynamic actin-rich structures that are related to cell migration and cancer cell invasion. It is required in the formation of functional podosomes, EGF-induced membrane ruffling, and lamellipodia generation. It plays an important role in cellular attachment and cell spreading. Tks4 is essential for the localization of MT1-MMP (membrane-type 1 matrix metalloproteinase) to invadopodia. It contains an N-terminal Phox homology (PX) domain and four SH3 domains. This model characterizes the second SH3 domain of Tks4. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 213009 [Multi-domain] Cd Length: 54 Bit Score: 38.47 E-value: 1.27e-03

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|..
gi 1804876928  923 KAQALCSWTAKKDNHLNFSKHDIITVLEQQ-ENWWFGEVHGGRGWFPKSYVK 973
Cdd:cd12076      2 KYTVIYPYTARDQDEINLEKGAVVEVIQKNlEGWWKIRYQGKEGWAPASYLK 53

EF-hand, calcium binding motif; A diverse superfamily of calcium sensors and calcium signal modulators; most examples in this alignment model have 2 active canonical EF hands. Ca2+ binding induces a conformational change in the EF-hand motif, leading to the activation or inactivation of target proteins. EF-hands tend to occur in pairs or higher copy numbers.

Pssm-ID: 238008 [Multi-domain] Cd Length: 63 Bit Score: 38.68 E-value: 1.28e-03

                           10        20        30        40        50        60
                   ....*....|....*....|....*....|....*....|....*....|....*....|...
gi 1804876928  283 KYRQKFNSLDKSMSGYLSGFQARNAL--LQSNLSQTQLATIWTLADIDGDGQLRAEEFILAMH 343
Cdd:cd00051      1 ELREAFRLFDKDGDGTISADELKAALksLGEGLSEEEIDEMIREVDKDGDGKIDFEEFLELMA 63

N-terminal Src homology 3 domain of Growth factor receptor-bound protein 2; GRB2 is a critical signaling molecule that regulates the Ras pathway by linking tyrosine kinases to the Ras guanine nucleotide releasing protein Sos (son of sevenless), which converts Ras to the active GTP-bound state. It is ubiquitously expressed in all tissues throughout development and is important in cell cycle progression, motility, morphogenesis, and angiogenesis. In lymphocytes, GRB2 is associated with antigen receptor signaling components. GRB2 contains an N-terminal SH3 domain, a central SH2 domain, and a C-terminal SH3 domain. Its N-terminal SH3 domain binds to Sos and Sos-derived proline-rich peptides. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212879 [Multi-domain] Cd Length: 56 Bit Score: 38.47 E-value: 1.28e-03

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|..
gi 1804876928  787 ALYRFEARSHDEMSFNSGDIIQV-DEKTigEPGWLYGSFQGNFGWFPCNYVE 837
Cdd:cd11946      5 AKYDFKATADDELSFKRGDILKVlNEEC--DQNWYKAELNGKDGFIPKNYIE 54

N-terminal Src Homology 3 domain of Ct10 Regulator of Kinase adaptor proteins; CRK adaptor proteins consists of SH2 and SH3 domains, which bind tyrosine-phosphorylated peptides and proline-rich motifs, respectively. They function downstream of protein tyrosine kinases in many signaling pathways started by various extracellular signals, including growth and differentiation factors. Cellular CRK (c-CRK) contains a single SH2 domain, followed by N-terminal and C-terminal SH3 domains. It is involved in the regulation of many cellular processes including cell growth, motility, adhesion, and apoptosis. CRK has been implicated in the malignancy of various human cancers. The N-terminal SH3 domain of CRK binds a number of target proteins including DOCK180, C3G, SOS, and cABL. The CRK family includes two alternatively spliced protein forms, CRKI and CRKII, that are expressed by the CRK gene, and the CRK-like (CRKL) protein, which is expressed by a distinct gene (CRKL). SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212692 [Multi-domain] Cd Length: 55 Bit Score: 38.50 E-value: 1.34e-03

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....
gi 1804876928 1006 EYI-ALYSYSSVEPGDLTFIEGEEILVTQKDGE-WWTG--SIGdRTGIFPSNYV 1055
Cdd:cd11758      1 EYVrALFDFPGNDDEDLPFKKGEILTVIRKPEEqWWNArnSEG-KTGMIPVPYV 53

Third Src Homology 3 domain of SH3 domain containing ring finger 3, an E3 ubiquitin-protein ligase; SH3RF3 is also called POSH2 (Plenty of SH3s 2) or SH3MD4 (SH3 multiple domains protein 4). It is a scaffold protein with E3 ubiquitin-protein ligase activity. It was identified in the screen for interacting partners of p21-activated kinase 2 (PAK2). It may play a role in regulating JNK mediated apoptosis in certain conditions. It also interacts with GTP-loaded Rac1. SH3RF3 is highly homologous to SH3RF1; it also contains an N-terminal RING finger domain and four SH3 domains. This model represents the third SH3 domain, located in the middle, of SH3RF3. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212858 Cd Length: 57 Bit Score: 38.44 E-value: 1.37e-03

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....
gi 1804876928 1007 YIALYSYSSVEPGDLTFIEGEEILVTQKDGEWWTGSIGDRT---GIFPSNYVKP 1057
Cdd:cd11925      3 YLALYAYKPQKNDELELRKGEMYRVIEKCQDGWFKGTSLRTgvsGVFPGNYVTP 56

Fourth N-terminal Src homology 3 domain of Dynamin Binding Protein, also called Tuba; DNMBP or Tuba is a cdc42-specific guanine nucleotide exchange factor (GEF) that contains four N-terminal SH3 domains, a central RhoGEF [or Dbl homology (DH)] domain followed by a Bin/Amphiphysin/Rvs (BAR) domain, and two C-terminal SH3 domains. It provides a functional link between dynamin and key regulatory proteins of the actin cytoskeleton. It plays an important role in regulating cell junction configuration. The four N-terminal SH3 domains of DNMBP bind the GTPase dynamin, which plays an important role in the fission of endocytic vesicles. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212731 Cd Length: 50 Bit Score: 38.17 E-value: 1.40e-03

                           10        20        30        40
                   ....*....|....*....|....*....|....*....|....*....
gi 1804876928 1008 IALYSYSSVEPGDLTFIEGEEILV--TQKDGeWWTGSIGDRTGIFPSNY 1054
Cdd:cd11797      3 VALYRFQALEPNELDFEVGDRIRIiaTLEDG-WLEGELKGRRGIFPHRF 50

Guanylate-binding protein, C-terminal domain; Guanylate-binding protein (GBP), C-terminal domain. Guanylate-binding proteins (GBPs) are synthesized after activation of the cell by interferons. The biochemical properties of GBPs are clearly different from those of Ras-like and heterotrimeric GTP-binding proteins. They bind guanine nucleotides with low affinity (micromolar range), are stable in their absence, and have a high turnover GTPase. In addition to binding GDP/GTP, they have the unique ability to bind GMP with equal affinity and hydrolyze GTP not only to GDP, but also to GMP. This C-terminal domain has been shown to mediate inhibition of endothelial cell proliferation by inflammatory cytokines.

Pssm-ID: 293879 [Multi-domain] Cd Length: 291 Bit Score: 42.56 E-value: 1.42e-03

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1804876928  415 EKRRQALMEQQQREAERKAQKEKEEWERKQRELQEQEWKKQLELEKRLEKqrelerqreeerrkeierreaaKQELERQR 494
Cdd:cd16269    195 EKEKEIEAERAKAEAAEQERKLLEEQQRELEQKLEDQERSYEEHLRQLKE----------------------KMEEEREN 252

                           90       100       110
                   ....*....|....*....|....*....|....*...
gi 1804876928  495 RL-EWERIRRQELLNQRNREQE----EIVRLNSKKKSL 527
Cdd:cd16269    253 LLkEQERALESKLKEQEALLEEgfkeQAELLQEEIRSL 290

Src homology 3 domain of ephexin-1-like SH3 domain containing Rho guanine nucleotide exchange factors; Members of this family contain RhoGEF (also called Dbl-homologous or DH), Pleckstrin Homology (PH), and C-terminal SH3 domains. They include the Rho guanine nucleotide exchange factors ARHGEF5, ARHGEF16, ARHGEF19, ARHGEF26, ARHGEF27 (also called ephexin-1), and similar proteins, and are also called ephexins because they interact directly with ephrin A receptors. GEFs interact with Rho GTPases via their DH domains to catalyze nucleotide exchange by stabilizing the nucleotide-free GTPase intermediate. They play important roles in neuronal development. The SH3 domains of ARHGEFs play an autoinhibitory role through intramolecular interactions with a proline-rich region N-terminal to the DH domain. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212727 [Multi-domain] Cd Length: 55 Bit Score: 38.47 E-value: 1.43e-03

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|..
gi 1804876928  924 AQALCSWTAKKDNHLNFSKHDIITVLEQQ-ENWWFGE--VHGGRGWFPKSYV 972
Cdd:cd11793      2 VQCVHAYTAQQPDELTLEEGDVVNVLRKMpDGWYEGErlRDGERGWFPSSYT 53

MAP7 (E-MAP-115) family; The organization of microtubules varies with the cell type and is presumably controlled by tissue-specific microtubule-associated proteins (MAPs). The 115-kDa epithelial MAP (E-MAP-115/MAP7) has been identified as a microtubule-stabilising protein predominantly expressed in cell lines of epithelial origin. The binding of this microtubule associated protein is nucleotide independent.

Pssm-ID: 461709 [Multi-domain] Cd Length: 153 Bit Score: 41.18 E-value: 1.45e-03

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1804876928  681 LLLKELResyntQQLALEQLHKIKRDKLKEIERKRSELIQKKKLEDEAIRKAKQGKENLwrESLRKEEEEKQKRLQEEKT 760
Cdd:pfam05672   43 LRKEELR-----RRAEEERARREEEARRLEEERRREEEERQRKAEEEAEEREQREQEEQ--ERLQKQKEEAEAKAREEAE 115

                           90
                   ....*....|....*
gi 1804876928  761 QEKVQEEERKVEEKQ 775
Cdd:pfam05672  116 RQRQEREKIMQQEEQ 130

Second Src Homology 3 domain of FCH and double SH3 domains protein 2; FCHSD2 has a domain structure consisting of an N-terminal F-BAR (FES-CIP4 Homology and Bin/Amphiphysin/Rvs), two SH3, and C-terminal proline-rich domains. It has only been characterized in silico and its function is unknown. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212827 Cd Length: 56 Bit Score: 38.38 E-value: 1.50e-03

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|..
gi 1804876928 1009 ALYSYSSVEPGDLTFIEGEEILV----TQKDGEWWTGSIGDRTGIFPSNYVK 1056
Cdd:cd11894      4 ALYDYEGQTDDELSFPEGAIIRIlnkeNQDDDGFWEGEFNGRIGVFPSVLVE 55

chromosome segregation protein SMC, common bacterial type; SMC (structural maintenance of chromosomes) proteins bind DNA and act in organizing and segregating chromosomes for partition. SMC proteins are found in bacteria, archaea, and eukaryotes. This family represents the SMC protein of most bacteria. The smc gene is often associated with scpB (TIGR00281) and scpA genes, where scp stands for segregation and condensation protein. SMC was shown (in Caulobacter crescentus) to be induced early in S phase but present and bound to DNA throughout the cell cycle. [Cellular processes, Cell division, DNA metabolism, Chromosome-associated proteins]

Pssm-ID: 274008 [Multi-domain] Cd Length: 1179 Bit Score: 43.51 E-value: 1.53e-03

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1804876928  404 KANYERGNVELEKRRQALMEQQQREAERKAQKEKEEWERKQRELQEQEWKKQLE-LEKRLEK-QRELERQREEERRKEIE 481
Cdd:TIGR02168  350 KEELESLEAELEELEAELEELESRLEELEEQLETLRSKVAQLELQIASLNNEIErLEARLERlEDRRERLQQEIEELLKK 429

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1804876928  482 RREAAKQELerQRRLEWERIRRQELLNQRNREQEEIVRLNSKKKSLHLELEALNGKHQQISGR---LQDVRLRKQT-QKT 557
Cdd:TIGR02168  430 LEEAELKEL--QAELEELEEELEELQEELERLEEALEELREELEEAEQALDAAERELAQLQARldsLERLQENLEGfSEG 507

                          170
                   ....*....|.
gi 1804876928  558 EIEVLDKQCDL 568
Cdd:TIGR02168  508 VKALLKNQSGL 518

Third Src homology 3 domain of Tyrosine kinase substrate (Tks) proteins; Tks proteins are Src substrates and scaffolding proteins that play important roles in the formation of podosomes and invadopodia, the dynamic actin-rich structures that are related to cell migration and cancer cell invasion. Vertebrates contain two Tks proteins, Tks4 (Tyr kinase substrate with four SH3 domains) and Tks5 (Tyr kinase substrate with five SH3 domains), which display partially overlapping but non-redundant functions. Both associate with the ADAMs family of transmembrane metalloproteases, which function as sheddases and mediators of cell and matrix interactions. Tks5 interacts with N-WASP and Nck, while Tks4 is essential for the localization of MT1-MMP (membrane-type 1 matrix metalloproteinase) to invadopodia. Tks proteins contain an N-terminal Phox homology (PX) domain and four or five SH3 domains. This model characterizes the third SH3 domain of Tks proteins. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212950 Cd Length: 53 Bit Score: 38.20 E-value: 1.55e-03

                           10        20        30        40
                   ....*....|....*....|....*....|....*....|....*
gi 1804876928 1158 DYVANNEDELNFSKGQLINVLNKDDPDWWQGEINGVTGLFPSNYV 1202
Cdd:cd12017      7 EFQATIQDGISFQKGQKVEVIDKNPSGWWYVKIDGKEGWAPSSYI 51

First Src Homology 3 domain (SH3A) of Cbl-interacting protein of 85 kDa; CIN85, also called SH3 domain-containing kinase-binding protein 1 (SH3KBP1) or CD2-binding protein 3 (CD2BP3) or Ruk, is an adaptor protein that is involved in the downregulation of receptor tyrosine kinases by facilitating endocytosis through interaction with endophilin-associated ubiquitin ligase Cbl proteins. It is also important in many other cellular processes including vesicle-mediated transport, cytoskeletal remodelling, apoptosis, cell adhesion and migration, and viral infection, among others. CIN85 exists as multiple variants from alternative splicing; the main variant contains three SH3 domains, a proline-rich region, and a C-terminal coiled-coil domain. All of these domains enable CIN85 to bind various protein partners and assemble complexes that have been implicated in many different functions. This alignment model represents the first SH3 domain (SH3A) of CIN85; SH3A binds to internal proline-rich motifs within the proline-rich region. This intramolecular interaction serves as a regulatory mechanism to keep CIN85 in a closed conformation, preventing the recruitment of other proteins. SH3A has also been shown to bind ubiquitin and to an atypical PXXXPR motif at the C-terminus of Cbl and the cytoplasmic end of the cell adhesion protein CD2. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212985 [Multi-domain] Cd Length: 53 Bit Score: 38.34 E-value: 1.57e-03

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|
gi 1804876928  789 YRFEARSHDEMSFNSGDIIQVDEKTIGepGWLYGSFQGNFGWFPCNYVEK 838
Cdd:cd12052      6 FDYKAQHEDELTITVGDIITKIKKDDG--GWWEGEIKGRRGLFPDNFVRE 53

phosphodiesterase; Provisional

Pssm-ID: 237177 [Multi-domain] Cd Length: 520 Bit Score: 43.23 E-value: 1.59e-03

                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 1804876928  702 KIKRDKLKEIERKRSELIQKKKLEDEAIRKAK--QGKENLWRESLRKEEEEKQKRLQEEKTQEKVQEEERKVEEKQ 775
Cdd:PRK12704    27 KIAEAKIKEAEEEAKRILEEAKKEAEAIKKEAllEAKEEIHKLRNEFEKELRERRNELQKLEKRLLQKEENLDRKL 102

Membrane protein TolA involved in colicin uptake [Cell wall/membrane/envelope biogenesis];

Pssm-ID: 442298 [Multi-domain] Cd Length: 485 Bit Score: 43.10 E-value: 1.63e-03

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1804876928  384 QKIQEEEPQKKLPVTFED-KRKANYERGNVELEKRRQALMEQQQREAERKAQKEKEEWERKQRELQEQEWKKQLELEKRL 462
Cdd:COG3064     58 REAKAEAEQRAAELAAEAaKKLAEAEKAAAEAEKKAAAEKAKAAKEAEAAAAAEKAAAAAEKEKAEEAKRKAEEEAKRKA 137

                           90       100       110       120       130
                   ....*....|....*....|....*....|....*....|....*....|....*.
gi 1804876928  463 EKQRELERQREEERRKEIERREAAKQELERQRRLEWERIRRQELLNQRNREQEEIV 518
Cdd:COG3064    138 EEERKAAEAEAAAKAEAEAARAAAAAAAAAAAAAARAAAGAAAALVAAAAAAVEAA 193

C-terminal (or second) Src homology 3 domain of VAV3 protein; VAV3 is ubiquitously expressed and functions as a phosphorylation-dependent guanine nucleotide exchange factor (GEF) for RhoA, RhoG, and Rac1. It has been implicated to function in the hematopoietic, bone, cerebellar, and cardiovascular systems. VAV3 is essential in axon guidance in neurons that control blood pressure and respiration. It is overexpressed in prostate cancer cells and it plays a role in regulating androgen receptor transcriptional activity. VAV proteins contain several domains that enable their function: N-terminal calponin homology (CH), acidic, RhoGEF (also called Dbl-homologous or DH), Pleckstrin Homology (PH), C1 (zinc finger), SH2, and two SH3 domains. The SH3 domain of VAV is involved in the localization of proteins to specific sites within the cell, by interacting with proline-rich sequences within target proteins. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212911 [Multi-domain] Cd Length: 56 Bit Score: 38.47 E-value: 1.66e-03

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|.
gi 1804876928 1008 IALYSYSSVEPGDLTFIEGEEILVTQKDGE--WWTGSIGDRTGIFPSNYVK 1056
Cdd:cd11978      4 IARYDFCARDMRELSLLKGDVVKIYTKMSTngWWRGEVNGRVGWFPSTYVE 54

Second Src homology 3 domain of ADAM-binding protein Eve-1; Eve-1, also called SH3 domain-containing protein 19 (SH3D19) or EEN-binding protein (EBP), exists in multiple alternatively spliced isoforms. The longest isoform contains five SH3 domain in the C-terminal region and seven proline-rich motifs in the N-terminal region. It is abundantly expressed in skeletal muscle and heart, and may be involved in regulating the activity of ADAMs (A disintegrin and metalloproteases). Eve-1 interacts with EEN, an endophilin involved in endocytosis and may be the target of the MLL-EEN fusion protein that is implicated in leukemogenesis. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212749 [Multi-domain] Cd Length: 52 Bit Score: 37.93 E-value: 1.71e-03

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|
gi 1804876928  788 LYRFEARSHDEMSFNSGDIIQVDEKTIGEpgWLYGSFQGNFGWFPCNYVE 837
Cdd:cd11815      5 LHDFPAEHSDDLSLNSGEIVYLLEKIDTE--WYRGKCKNTTGIFPANHVK 52

Src Homology 3 domain of metazoan osteoclast stimulating factor 1; OSTF1, also named OSF or SH3P2, is a signaling protein containing SH3 and ankyrin-repeat domains. It acts through a Src-related pathway to enhance the formation of osteoclasts and bone resorption. It also acts as a negative regulator of cell motility. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212706 [Multi-domain] Cd Length: 53 Bit Score: 38.05 E-value: 1.74e-03

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|
gi 1804876928 1084 AYVASGSEQLSLAPGQLILILKKNSSGWWQGELqargkKRQKGWFPASHV 1133
Cdd:cd11772      7 DYEAQHPDELSFEEGDLLYISDKSDPNWWKATC-----GGKTGLIPSNYV 51

Src homology 3 domain of the Rho guanine nucleotide exchange factors ARHGEF5 and ARHGEF19; ARHGEF5, also called ephexin-3 or TIM (Transforming immortalized mammary oncogene), is a potent activator of RhoA and it plays roles in regulating cell shape, adhesion, and migration. It binds to the SH3 domain of Src and is involved in regulating Src-induced podosome formation. ARHGEF19, also called ephexin-2 or WGEF (weak-similarity GEF), is highly expressed in the intestine, liver, heart and kidney. It activates RhoA, Cdc42, and Rac 1, and has been shown to activate RhoA in the Wnt-PCP (planar cell polarity) pathway. It is involved in the regulation of cell polarity and cytoskeletal reorganization. ARHGEF5 and ARHGEF19 contain RhoGEF (also called Dbl-homologous or DH), Pleckstrin Homology (PH), and SH3 domains. The SH3 domains of ARHGEFs play an autoinhibitory role through intramolecular interactions with a proline-rich region N-terminal to the DH domain. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212873 Cd Length: 55 Bit Score: 38.23 E-value: 1.74e-03

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|..
gi 1804876928  925 QALCSWTAKKDNHLNFSKHDIITVLEQQENWWFGEVH---GGRGWFPKSYVK 973
Cdd:cd11940      3 QCIRSYKAQENDELTLEKADIIMVRQQSSDGWLEGVRlsdGERGWFPQSHVE 54

Src homology 3 domain of Src Protein Tyrosine Kinase; Src (or c-Src) is a cytoplasmic (or non-receptor) PTK and is the vertebrate homolog of the oncogenic protein (v-Src) from Rous sarcoma virus. Together with other Src subfamily proteins, it is involved in signaling pathways that regulate cytokine and growth factor responses, cytoskeleton dynamics, cell proliferation, survival, and differentiation. Src also play a role in regulating cell adhesion, invasion, and motility in cancer cells, and tumor vasculature, contributing to cancer progression and metastasis. Elevated levels of Src kinase activity have been reported in a variety of human cancers. Several inhibitors of Src have been developed as anti-cancer drugs. Src is also implicated in acute inflammatory responses and osteoclast function. Src kinases contain an N-terminal SH4 domain with a myristoylation site, followed by SH3 and SH2 domains, a tyr kinase domain, and a regulatory C-terminal region containing a conserved tyr. They are activated by autophosphorylation at the tyr kinase domain, but are negatively regulated by phosphorylation at the C-terminal tyr by Csk (C-terminal Src Kinase). The SH3 domain of Src kinases contributes to substrate recruitment by binding adaptor proteins/substrates, and regulation of kinase activity through an intramolecular interaction. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212941 [Multi-domain] Cd Length: 56 Bit Score: 38.17 E-value: 1.76e-03

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|...
gi 1804876928  785 YKALYRFEARSHDEMSFNSGDIIQVDEKTIGEpGWLYGSFQ-GNFGWFPCNYV 836
Cdd:cd12008      2 FVALYDYESRTETDLSFKKGERLQIVNNTEGD-WWLAHSLTtGQTGYIPSNYV 53

First C-terminal Src homology 3 domain of Fungal Actin-binding protein 1; Abp1 is an adaptor protein that functions in receptor-mediated endocytosis and vesicle trafficking. It contains an N-terminal actin-binding module, the actin-depolymerizing factor (ADF) homology domain, a central proline-rich region, and a C-terminal SH3 domain (many yeast Abp1 proteins contain two C-terminal SH3 domains). Yeast Abp1 also contains two acidic domains that bind directly to the Arp2/3 complex, which is required to initiate actin polymerization. The SH3 domain of yeast Abp1 binds and localizes the kinases, Ark1p and Prk1p, which facilitate actin patch disassembly following vesicle internalization. It also mediates the localization to the actin patch of the synaptojanin-like protein, Sjl2p, which plays a key role in endocytosis. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212895 [Multi-domain] Cd Length: 54 Bit Score: 38.24 E-value: 1.81e-03

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....*..
gi 1804876928 1079 AQVTSAYVASGSEQLSLAPGQLILILKKNSSGWWQGElqarGKKRQKGWFPASHVKL 1135
Cdd:cd11962      2 AVVLYDYEKDEDNEIELVEGEIVTNIEMVDEDWWMGT----NSKGESGLFPSNYVEL 54

N-terminal Src Homology 3 domain of Ct10 Regulator of Kinase adaptor proteins; CRK adaptor proteins consists of SH2 and SH3 domains, which bind tyrosine-phosphorylated peptides and proline-rich motifs, respectively. They function downstream of protein tyrosine kinases in many signaling pathways started by various extracellular signals, including growth and differentiation factors. Cellular CRK (c-CRK) contains a single SH2 domain, followed by N-terminal and C-terminal SH3 domains. It is involved in the regulation of many cellular processes including cell growth, motility, adhesion, and apoptosis. CRK has been implicated in the malignancy of various human cancers. The N-terminal SH3 domain of CRK binds a number of target proteins including DOCK180, C3G, SOS, and cABL. The CRK family includes two alternatively spliced protein forms, CRKI and CRKII, that are expressed by the CRK gene, and the CRK-like (CRKL) protein, which is expressed by a distinct gene (CRKL). SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212692 [Multi-domain] Cd Length: 55 Bit Score: 38.11 E-value: 1.82e-03

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|...
gi 1804876928  786 KALYRFEARSHDEMSFNSGDIIQVDEKTiGEPGWLYGSFQGNFGWFPCNYVEK 838
Cdd:cd11758      4 RALFDFPGNDDEDLPFKKGEILTVIRKP-EEQWWNARNSEGKTGMIPVPYVEK 55

Src homology 3 domain of SH3 and multiple ankyrin repeat domains protein 1; Shank1, also called SSTRIP (Somatostatin receptor-interacting protein), is a brain-specific protein that plays a role in the construction of postsynaptic density (PSD) and the maturation of dendritic spines. Mice deficient in Shank1 show altered PSD composition, thinner PSDs, smaller dendritic spines, and weaker basal synaptic transmission, although synaptic plasticity is normal. They show increased anxiety and impaired fear memory, but also show better spatial learning. Shank proteins carry scaffolding functions through multiple sites of protein-protein interaction in its domain architecture, including ankyrin (ANK) repeats, a long proline rich region, as well as SH3, PDZ, and SAM domains. The SH3 domain of Shank binds GRIP, a scaffold protein that binds AMPA receptors and Eph receptors/ligands. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212915 [Multi-domain] Cd Length: 52 Bit Score: 38.07 E-value: 1.82e-03

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|
gi 1804876928 1007 YIALYSYSSVEPGDLTFIEGEEILV-TQKDGEWWTGSIGDRTGIFPSNYV 1055
Cdd:cd11982      3 FMAVKPYQSQAEGEISLSKGEKIKVlSVGEGGFWEGQVKGRVGWFPSDCV 52

Second Src homology 3 domain of Tyrosine kinase substrate (Tks) proteins; Tks proteins are Src substrates and scaffolding proteins that play important roles in the formation of podosomes and invadopodia, the dynamic actin-rich structures that are related to cell migration and cancer cell invasion. Vertebrates contain two Tks proteins, Tks4 (Tyr kinase substrate with four SH3 domains) and Tks5 (Tyr kinase substrate with five SH3 domains), which display partially overlapping but non-redundant functions. Both associate with the ADAMs family of transmembrane metalloproteases, which function as sheddases and mediators of cell and matrix interactions. Tks5 interacts with N-WASP and Nck, while Tks4 is essential for the localization of MT1-MMP (membrane-type 1 matrix metalloproteinase) to invadopodia. Tks proteins contain an N-terminal Phox homology (PX) domain and four or five SH3 domains. This model characterizes the second SH3 domain of Tks proteins. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212949 Cd Length: 54 Bit Score: 38.21 E-value: 1.87e-03

                           10        20        30        40
                   ....*....|....*....|....*....|....*....|....*..
gi 1804876928  929 SWTAKKDNHLNFSKHDIITVLEQQ-ENWWFGEVHGGRGWFPKSYVKI 974
Cdd:cd12016      8 AYKAENEDEIGFETGVVVEVIQKNlDGWWKIRYQGKEGWAPATYLKK 54

Src homology 3 domain of Phospholipase C (PLC) gamma 2; PLCgamma2 is primarily expressed in haematopoietic cells, specifically in B cells. It is activated by tyrosine phosphorylation by B cell receptor (BCR) kinases and is recruited to the plasma membrane where its substrate is located. It is required in pre-BCR signaling and in the maturation of B cells. PLCs catalyze the hydrolysis of phosphatidylinositol (4,5)-bisphosphate [PtdIns(4,5)P2] to produce Ins(1,4,5)P3 and diacylglycerol (DAG). Ins(1,4,5)P3 initiates the calcium signaling cascade while DAG functions as an activator of PKC. PLCgamma contains a Pleckstrin homology (PH) domain followed by an elongation factor (EF) domain, two catalytic regions of PLC domains that flank two tandem SH2 domains, followed by a SH3 domain and C2 domain. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212902 Cd Length: 55 Bit Score: 37.90 E-value: 1.88e-03

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|
gi 1804876928 1085 YVASGSEQLSLAPGQLILILKKNSSGWWQGELqarGKKRQKgWFPASHVK 1134
Cdd:cd11969      8 YRAKRSDELSFCKGALIHNVSKETGGWWKGDY---GGKVQH-YFPSNYVE 53

Third Src Homology 3 domain of the fungal endocytic adaptor protein Sla1p; Sla1p facilitates endocytosis by playing a role as an adaptor protein in coupling components of the actin cytoskeleton to the endocytic machinery. It interacts with Abp1p, Las17p and Pan1p, which are activator proteins of actin-related protein 2/3 (Arp2/3). Sla1p contains multiple domains including three SH3 domains, a SAM (sterile alpha motif) domain, and a Sla1 homology domain 1 (SHD1), which binds to the NPFXD motif that is found in many integral membrane proteins such as the Golgi-localized Arf-binding protein Lsb5p and the P4-ATPases, Drs2p and Dnf1p. The third SH3 domain of Sla1p can bind ubiquitin while retaining the ability to bind proline-rich ligands; monoubiquitination of target proteins signals internalization and sorting through the endocytic pathway. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212709 [Multi-domain] Cd Length: 57 Bit Score: 38.07 E-value: 1.88e-03

                           10        20        30        40        50        60
                   ....*....|....*....|....*....|....*....|....*....|....*....|
gi 1804876928 1077 EIAQVTSAYVASGSEQLSLAPGQLILIL-KKNSSGWWQGELQARGkkrQKGWFPASHVKL 1135
Cdd:cd11775      1 KRGKVLYDFDAQSDDELTVKEGDVVYILdDKKSKDWWMVENVSTG---KEGVVPASYIEI 57

Src Homology 3 domain of CASK interacting protein 2; Caskin2 is a multidomain adaptor protein that contains six ankyrin repeats, a single SH3 domain, tandem sterile alpha motif (SAM) domains, and a long disordered proline-rich region. It shares a domain architecture with Caskin1, but does not bind CASK. The function of Caskin2 is still unknown. SH3 domains bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs; they play a role in the regulation of enzymes by intramolecular interactions, changing the subcellular localization of signal pathway components and mediate multiprotein complex assemblies.

Pssm-ID: 212996 Cd Length: 62 Bit Score: 38.41 E-value: 1.97e-03

                           10        20        30        40        50        60
                   ....*....|....*....|....*....|....*....|....*....|....*....|..
gi 1804876928  922 LKAQALCS-WTAKKDNHLNFSKHDIITVLEQQ-ENWWFGEVHGGR------GWFPKSYVKII 975
Cdd:cd12063      1 LKVRALKDfWNLHDPTALNVRAGDVITVLEQHpDGRWKGHIHDSQrgtdrvGYFPPSIVEVI 62

NIMA-related protein kinase; Provisional

Pssm-ID: 173502 [Multi-domain] Cd Length: 1021 Bit Score: 43.19 E-value: 1.97e-03

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1804876928  404 KANYERGNVELEKRRQALMEQQQREAERKAQKEKEEWERKQRELQEQEWKKQLELEkRLEKQrelerqreeerrkeierr 483
Cdd:PTZ00266   432 KDHAERARIEKENAHRKALEMKILEKKRIERLEREERERLERERMERIERERLERE-RLERE------------------ 492

                           90       100       110       120
                   ....*....|....*....|....*....|....*....|.
gi 1804876928  484 EAAKQELERQR--RLEWERIRRQEllnqrnREQEEIVRLNS 522
Cdd:PTZ00266   493 RLERDRLERDRldRLERERVDRLE------RDRLEKARRNS 527

First Src Homology 3 domain (SH3A) of CD2-associated protein and similar proteins; This subfamily is composed of the first SH3 domain (SH3A) of CD2AP, CIN85 (Cbl-interacting protein of 85 kDa), and similar domains. CD2AP and CIN85 are adaptor proteins that bind to protein partners and assemble complexes that have been implicated in T cell activation, kidney function, and apoptosis of neuronal cells. They also associate with endocytic proteins, actin cytoskeleton components, and other adaptor proteins involved in receptor tyrosine kinase (RTK) signaling. CD2AP and the main isoform of CIN85 contain three SH3 domains, a proline-rich region, and a C-terminal coiled-coil domain. All of these domains enable CD2AP and CIN85 to bind various protein partners and assemble complexes that have been implicated in many different functions. SH3A of both proteins bind to an atypical PXXXPR motif at the C-terminus of Cbl and the cytoplasmic domain of the cell adhesion protein CD2. CIN85 SH3A binds to internal proline-rich motifs within the proline-rich region; this intramolecular interaction serves as a regulatory mechanism to keep CIN85 in a closed conformation, preventing the recruitment of other proteins. CIN85 SH3A has also been shown to bind ubiquitin. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212806 [Multi-domain] Cd Length: 53 Bit Score: 38.02 E-value: 2.04e-03

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|
gi 1804876928 1085 YVASGSEQLSLAPGQLILILKKNSSGWWQGELQARgkkrqKGWFPASHVK 1134
Cdd:cd11873      8 YDAEEPDELTLKVGDIITNVKKMEEGWWEGTLNGK-----RGMFPDNFVK 52

C-terminal Src Homology 3 domain of the p67phox subunit of NADPH oxidase and similar proteins; This subfamily is composed of p67phox, NADPH oxidase activator 1 (Noxa1), and similar proteins. p67phox, also called Neutrophil cytosol factor 2 (NCF-2), and Noxa1 are homologs and are the cytosolic subunits of the phagocytic (Nox2) and nonphagocytic (Nox1) NADPH oxidase complexes, respectively. NADPH oxidase catalyzes the transfer of electrons from NADPH to oxygen during phagocytosis forming superoxide and reactive oxygen species. p67phox and Noxa1 play regulatory roles. p67phox contains N-terminal TPR, first SH3 (or N-terminal or central SH3), PB1, and C-terminal SH3 domains. Noxa1 has a similar domain architecture except it is lacking the N-terminal SH3 domain. The TPR domain of both binds activated GTP-bound Rac, while the C-terminal SH3 domain of p67phox and Noxa1 binds the polyproline motif found at the C-terminus of p47phox and Noxo1, respectively. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212803 [Multi-domain] Cd Length: 53 Bit Score: 37.89 E-value: 2.05e-03

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....*
gi 1804876928  787 ALYRFEARSHDEMSFNSGDII----QVDEKtigepgWLYGSFQGNFGWFPCNYVE 837
Cdd:cd11870      4 ALHRYEAQGPEDLGFREGDTIdvlsEVNEA------WLEGHSDGRVGIFPKCFVV 52

Src homology 3 domain of the Rho guanine nucleotide exchange factor, ephexin-1 (also called NGEF or ARHGEF27); Ephexin-1, also called NGEF (neuronal GEF) or ARHGEF27, activates RhoA, Tac1, and Cdc42 by exchanging bound GDP for free GTP. It is expressed mainly in the brain in a region associated with movement control. It regulates the stability of postsynaptic acetylcholine receptor (AChR) clusters and thus, plays a critical role in the maturation and neurotransmission of neuromuscular junctions. Ephexin-1 directly interacts with the ephrin receptor EphA4 and their coexpression enhances the ability of ephexin-1 to activate RhoA. It is required for normal axon growth and EphA-induced growth cone collapse. Ephexin-1 contains RhoGEF (also called Dbl-homologous or DH), Pleckstrin Homology (PH), and SH3 domains. The SH3 domains of ARHGEFs play an autoinhibitory role through intramolecular interactions with a proline-rich region N-terminal to the DH domain. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212872 [Multi-domain] Cd Length: 55 Bit Score: 38.00 E-value: 2.06e-03

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....
gi 1804876928  923 KAQALCSWTAKKDNHLNFSKHDIITVLEQQEN-WWFGE-VHGG-RGWFPKSYVK 973
Cdd:cd11939      1 QVQCVHPYVSQEPDELSLELADVLNILDKTDDgWIFGErLHDQeRGWFPSSVVE 54

First Src Homology 3 domain of SH3 domain containing ring finger proteins; This model represents the first SH3 domain of SH3RF1 (or POSH), SH3RF2 (or POSHER), SH3RF3 (POSH2), and similar domains. Members of this family are scaffold proteins that function as E3 ubiquitin-protein ligases. They all contain an N-terminal RING finger domain and multiple SH3 domains; SH3RF1 and SH3RF3 have four SH3 domains while SH3RF2 has three. SH3RF1 plays a role in calcium homeostasis through the control of the ubiquitin domain protein Herp. It may also have a role in regulating death receptor mediated and JNK mediated apoptosis. SH3RF3 interacts with p21-activated kinase 2 (PAK2) and GTP-loaded Rac1. It may play a role in regulating JNK mediated apoptosis in certain conditions. SH3RF2 acts as an anti-apoptotic regulator of the JNK pathway by binding to and promoting the degradation of SH3RF1. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212720 [Multi-domain] Cd Length: 53 Bit Score: 37.73 E-value: 2.09e-03

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|.
gi 1804876928 1084 AYVASGSEQLSLAPGQLILILKKNSSGWWQGELQArgkkrQKGWFPASHVK 1134
Cdd:cd11786      7 NYEGKEPGDLSFKKGDIILLRKRIDENWYHGECNG-----KQGFFPASYVQ 52

Src Homology 3 domain of Sorting Nexin 33; SNX33 interacts with Wiskott-Aldrich syndrome protein (WASP) and plays a role in the maintenance of cell shape and cell cycle progression. It modulates the shedding and endocytosis of cellular prion protein (PrP(c)) and amyloid precursor protein (APP). SNXs are Phox homology (PX) domain containing proteins that are involved in regulating membrane traffic and protein sorting in the endosomal system. SNX33 also contains BAR and SH3 domains. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212829 [Multi-domain] Cd Length: 55 Bit Score: 38.02 E-value: 2.10e-03

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|..
gi 1804876928 1155 AMYDYVANNEDELNFSKGQLINVLNKDDPD-WWQGEIN-GVTGLFPSNYVKM 1204
Cdd:cd11896      4 ALYSFQSENKEEINIQENEELVIFSENSLDgWLQGQNSrGETGLFPASYVEI 55

Src homology 3 domain of SH3 and multiple ankyrin repeat domains protein 3; Shank3, also called ProSAP2 (Proline-rich synapse-associated protein 2), is widely expressed. It plays a role in the formation of dendritic spines and synapses. Haploinsufficiency of the Shank3 gene causes the 22q13 deletion/Phelan-McDermid syndrome, and variants of Shank3 have been implicated in autism spectrum disorder, schizophrenia, and intellectual disability. Shank proteins carry scaffolding functions through multiple sites of protein-protein interaction in its domain architecture, including ankyrin (ANK) repeats, a long proline rich region, as well as SH3, PDZ, and SAM domains. The SH3 domain of Shank binds GRIP, a scaffold protein that binds AMPA receptors and Eph receptors/ligands. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212917 Cd Length: 52 Bit Score: 38.01 E-value: 2.16e-03

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|
gi 1804876928 1007 YIALYSYSSVEPGDLTFIEGEEILVTQ-KDGEWWTGSIGDRTGIFPSNYV 1055
Cdd:cd11984      3 FIAVKAYSPQGEGEIQLNRGERVKVLSiGEGGFWEGTVKGRTGWFPADCV 52

Src Homology 3 domain of Calcium/calmodulin-dependent Serine protein Kinase; CASK is a scaffolding protein that is highly expressed in the mammalian nervous system and plays roles in synaptic protein targeting, neural development, and gene expression regulation. CASK interacts with many different binding partners including parkin, neurexin, syndecans, calcium channel proteins, caskin, among others, to perform specific functions in different subcellular locations. Disruption of the CASK gene in mice results in neonatal lethality while mutations in the human gene have been associated with X-linked mental retardation. Drosophila CASK is associated with both pre- and postsynaptic membranes and is crucial in synaptic transmission and vesicle cycling. CASK contains an N-terminal calmodulin-dependent kinase (CaMK)-like domain, two L27 domains, followed by the core of three domains characteristic of MAGUK (membrane-associated guanylate kinase) proteins: PDZ, SH3, and guanylate kinase (GuK). In addition, it also contains the Hook (Protein 4.1 Binding) motif in between the SH3 and GuK domains. The GuK domain in MAGUK proteins is enzymatically inactive; instead, the domain mediates protein-protein interactions and associates intramolecularly with the SH3 domain. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 213014 Cd Length: 62 Bit Score: 37.96 E-value: 2.17e-03

                           10        20        30
                   ....*....|....*....|....*....|....*..
gi 1804876928 1167 LNFSKGQLINVLNKDDPDWWQGE----INGVTGLFPS 1199
Cdd:cd12081     23 IRFRVGDILQIISKDDHNWWQAKlensKNGTAGLIPS 59

Second or C-terminal Src homology 3 domain of the p47phox subunit of NADPH oxidase, also called Neutrophil Cytosolic Factor 1; p47phox, or NCF1, is a cytosolic subunit of the phagocytic NADPH oxidase complex (also called Nox2 or gp91phox), which plays a key role in the ability of phagocytes to defend against bacterial infections. NADPH oxidase catalyzes the transfer of electrons from NADPH to oxygen during phagocytosis forming superoxide and reactive oxygen species. p47phox is required for activation of NADH oxidase and plays a role in translocation. It contains an N-terminal Phox homology (PX) domain, tandem SH3 domains (N-SH3 and C-SH3), a polybasic/autoinhibitory region, and a C-terminal proline-rich region (PRR). This model characterizes the second SH3 domain (or C-SH3) of p47phox. In its inactive state, the tandem SH3 domains interact intramolecularly with the autoinhibitory region; upon activation, the tandem SH3 domains are exposed through a conformational change, resulting in their binding to the PRR of p22phox and the activation of NADPH oxidase. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212955 [Multi-domain] Cd Length: 53 Bit Score: 37.90 E-value: 2.19e-03

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|
gi 1804876928 1154 IAMYDYVANNEDELNFSKGQLINVLNKDDPDWWQGEINGVTGLFPSNYVK 1203
Cdd:cd12022      3 ITIKAYTAVEEDELTLLEGEAIEVIHKLLDGWWVVRKGEVTGYFPSMYLQ 52

Src homology 3 domain of RUN and SH3 domain-containing protein 1; RUSC1, also called NESCA (New molecule containing SH3 at the carboxy-terminus), is highly expressed in the brain and is translocated to the nuclear membrane from the cytoplasm upon stimulation with neurotrophin. It plays a role in facilitating neurotrophin-dependent neurite outgrowth. It also interacts with NEMO (or IKKgamma) and may function in NEMO-mediated activation of NF-kB. RUSC proteins are adaptor proteins consisting of RUN, leucine zipper, and SH3 domains. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212891 [Multi-domain] Cd Length: 51 Bit Score: 37.89 E-value: 2.20e-03

                           10        20        30        40
                   ....*....|....*....|....*....|....*....|....*....
gi 1804876928 1153 VIAMYDYVANnEDELNFSKGQLINVLNKDDPDWWQGEINGVTGLFPSNY 1201
Cdd:cd11958      2 VRALCDHAGS-ESQLSFRKGEELQVLGTVDEDWIRCRRGDREGLVPVGY 49

Src homology 3 domain of the CAS (Crk-Associated Substrate) scaffolding protein family member, Breast Cancer Anti-estrogen Resistance 1; BCAR1, also called p130cas or CASS1, is the founding member of the CAS family of scaffolding proteins and was originally identified through its ability to associate with Crk. The name BCAR1 was designated because the human gene was identified in a screen for genes that promote resistance to tamoxifen. It is widely expressed and its deletion is lethal in mice. It plays a role in regulating cell motility, survival, proliferation, transformation, cancer progression, and bacterial pathogenesis. CAS proteins function as molecular scaffolds to regulate protein complexes that are involved in many cellular processes. They share a common domain structure that includes an N-terminal SH3 domain, an unstructured substrate domain that contains many YxxP motifs, a serine-rich four-helix bundle, and a FAT-like C-terminal domain. The SH3 domain of CAS proteins binds to diverse partners including FAK, FRNK, Pyk2, PTP-PEST, DOCK180, among others. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212934 Cd Length: 68 Bit Score: 38.48 E-value: 2.21e-03

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|
gi 1804876928  786 KALYRFEARSHDEMSFNSGDIIQV-DEKTIGEPGWLYGSFQGNFGWFPCN 834
Cdd:cd12001      6 KALYDNVAESPDELSFRKGDIMTVlERDTQGLDGWWLCSLHGRQGIVPGN 55

Second Src Homology 3 domain (SH3B) of Cbl-interacting protein of 85 kDa; CIN85, also called SH3 domain-containing kinase-binding protein 1 (SH3KBP1) or CD2-binding protein 3 (CD2BP3) or Ruk, is an adaptor protein that is involved in the downregulation of receptor tyrosine kinases by facilitating endocytosis through interaction with endophilin-associated ubiquitin ligase Cbl proteins. It is also important in many other cellular processes including vesicle-mediated transport, cytoskeletal remodelling, apoptosis, cell adhesion and migration, and viral infection, among others. CIN85 exists as multiple variants from alternative splicing; the main variant contains three SH3 domains, a proline-rich region, and a C-terminal coiled-coil domain. All of these domains enable CIN85 to bind various protein partners and assemble complexes that have been implicated in many different functions. This alignment model represents the second SH3 domain (SH3B) of CIN85. SH3B has been shown to bind Cbl proline-rich peptides and ubiquitin. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212988 [Multi-domain] Cd Length: 53 Bit Score: 37.67 E-value: 2.32e-03

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....*
gi 1804876928 1080 QVTSAYVASGSEQLSLAPGQLILILKKNSSGWWQGELQARgkkrqKGWFPASHVK 1134
Cdd:cd12055      3 QVAFSYLPQNEDELELKVGDIIEVVGEVEEGWWEGVLNGK-----TGMFPSNFIK 52

Hyaluronan mediated motility receptor N-terminal; HMMR_N is the N-terminal region of eukaryotic hyaluronan-mediated motility receptor proteins. The protein is functionally associated with BRCA1 and thus predicted to be a common, low-penetrance breast cancer candidate.

Pssm-ID: 464932 [Multi-domain] Cd Length: 329 Bit Score: 42.11 E-value: 2.34e-03

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1804876928  423 EQQQREAERKAQKEKEEWERKQ-RELQEQEwKKQLELEKRLEKqrelERQREEERRKEIERREAAKQELERQRRlewERI 501
Cdd:pfam15905   64 KSQKNLKESKDQKELEKEIRALvQERGEQD-KRLQALEEELEK----VEAKLNAAVREKTSLSASVASLEKQLL---ELT 135

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1804876928  502 RRQELL------------------------NQRNREQEEIV----RLNSKKKSLHLELEALNGKHQQISGRLQDVRLRKQ 553
Cdd:pfam15905  136 RVNELLkakfsedgtqkkmsslsmelmklrNKLEAKMKEVMakqeGMEGKLQVTQKNLEHSKGKVAQLEEKLVSTEKEKI 215

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1804876928  554 TQKTEIEVLDKqcdlEIMEIKQLQQELQDYQNKLIYLvpeKQLLNERIKNMQ-LGNTPDLGIDLLHKKSLEKEELCQRLK 632
Cdd:pfam15905  216 EEKSETEKLLE----YITELSCVSEQVEKYKLDIAQL---EELLKEKNDEIEsLKQSLEEKEQELSKQIKDLNEKCKLLE 288

                          250       260
                   ....*....|....*....|....*...
gi 1804876928  633 EQLDALEKETASK----LSEMDSFNNQL 656
Cdd:pfam15905  289 SEKEELLREYEEKeqtlNAELEELKEKL 316

Second Src Homology 3 domain of FCH and double SH3 domains proteins; This group is composed of FCH and double SH3 domains protein 1 (FCHSD1) and FCHSD2. These proteins have a common domain structure consisting of an N-terminal F-BAR (FES-CIP4 Homology and Bin/Amphiphysin/Rvs), two SH3, and C-terminal proline-rich domains. They have only been characterized in silico and their functions remain unknown. This group also includes the insect protein, nervous wreck, which acts as a regulator of synaptic growth signaling. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212696 [Multi-domain] Cd Length: 57 Bit Score: 37.76 E-value: 2.37e-03

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|
gi 1804876928 1085 YVASGSEQLSLAPGQLILILKKNSS----GWWQGELQARgkkrqKGWFPA 1130
Cdd:cd11762      8 YEAQSDEELSFPEGAIIRILRKDDNgvddGWWEGEFNGR-----VGVFPS 52

First Src Homology 3 domain of Nck1 adaptor protein; Nck1 (also called Nckalpha) plays a crucial role in connecting signaling pathways of tyrosine kinase receptors and important effectors in actin dynamics and cytoskeletal remodeling. It binds and activates RasGAP, resulting in the downregulation of Ras. It is also involved in the signaling of endothilin-mediated inhibition of cell migration. Nck adaptor proteins regulate actin cytoskeleton dynamics by linking proline-rich effector molecules to protein tyrosine kinases and phosphorylated signaling intermediates. They contain three SH3 domains and a C-terminal SH2 domain. They function downstream of the PDGFbeta receptor and are involved in Rho GTPase signaling and actin dynamics. Vertebrates contain two Nck adaptor proteins: Nck1 (also called Nckalpha) and Nck2, which show partly overlapping functions but also bind distinct targets. The first SH3 domain of Nck1 binds the PxxDY sequence in the CD3e cytoplasmic tail; this binding inhibits phosphorylation by Src kinases, resulting in the downregulation of TCR surface expression. SH3 domains are protein interaction domains that usually bind to proline-rich ligands with moderate affinity and selectivity, preferentially a PxxP motif. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212833 [Multi-domain] Cd Length: 59 Bit Score: 37.78 E-value: 2.39e-03

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|..
gi 1804876928 1153 VIAMYDYVANNEDELNFSKGQLINVLNkDDPDWWQ-GEINGVTGLFPSNYVK 1203
Cdd:cd11900      5 VVAKFDYVAQQDQELDIKKNERLWLLD-DSKSWWRvRNAMNKTGFVPSNYVE 55

Borrelia P83/100 protein; This family consists of several Borrelia P83/P100 antigen proteins.

Pssm-ID: 114011 [Multi-domain] Cd Length: 489 Bit Score: 42.68 E-value: 2.44e-03

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1804876928  411 NVELEKRRQALMEQQQREAERKAQKEKEEWERKQRELQEQEWKKQLElEKRLEKQreLERQREEERRKEIERREAAKQEL 490
Cdd:pfam05262  193 GVNFRRDMTDLKERESQEDAKRAQQLKEELDKKQIDADKAQQKADFA-QDNADKQ--RDEVRQKQQEAKNLPKPADTSSP 269

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1804876928  491 ERQRRLEWERIRRQELLNQRNREQEEIVRLNSKKKSLHLELEA-------------LNGKHQQISGRLQDVRLRKQTQKT 557
Cdd:pfam05262  270 KEDKQVAENQKREIEKAQIEIKKNDEEALKAKDHKAFDLKQESkasekeaedkeleAQKKREPVAEDLQKTKPQVEAQPT 349

                          170       180       190       200       210
                   ....*....|....*....|....*....|....*....|....*....|....*..
gi 1804876928  558 E--------------IEVLDKQCDLEIMEIKQLQQE-------LQDYQNKLIYLVPE 593
Cdd:pfam05262  350 SlnedaidssnpvygLKVVDPITNLSELVLIDLKTEvrlresaQQTIRRRGLYEREK 406

First Src Homology 3 domain of Vinexin, also called Sorbin and SH3 domain containing 3 (Sorbs3); Vinexin is also called Sorbs3, SH3P3, and SH3-containing adapter molecule 1 (SCAM-1). It is an adaptor protein containing one sorbin homology (SoHo) and three SH3 domains. Vinexin was first identified as a vinculin binding protein; it is co-localized with vinculin at cell-ECM and cell-cell adhesion sites. There are several splice variants of vinexin: alpha, which contains the SoHo and three SH3 domains and displays tissue-specific expression; and beta, which contains only the three SH3 domains and is widely expressed. Vinexin alpha stimulates the accumulation of F-actin at focal contact sites. Vinexin also promotes keratinocyte migration and wound healing. The SH3 domains of vinexin have been reported to bind a number of ligands including vinculin, WAVE2, DLG5, Abl, and Cbl. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212854 Cd Length: 55 Bit Score: 37.59 E-value: 2.52e-03

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|..
gi 1804876928  786 KALYRFEARSHDEMSFNSGDIIQVDEKTigEPGWLYGSFQGNFGWFPCNYVE 837
Cdd:cd11921      4 RLKFDFQAQSPKELTLQKGDIVYIHKEV--DKNWLEGEHHGRVGIFPANYVE 53

First Src Homology 3 domain of Sorbin and SH3 domain containing 1 (Sorbs1), also called ponsin; Sorbs1 is also called ponsin, SH3P12, or CAP (c-Cbl associated protein). It is an adaptor protein containing one sorbin homology (SoHo) and three SH3 domains. It binds Cbl and plays a major role in regulating the insulin signaling pathway by enhancing insulin-induced phosphorylation of Cbl. Sorbs1, like vinexin, localizes at cell-ECM and cell-cell adhesion sites where it binds vinculin, paxillin, and afadin. It may function in the control of cell motility. Other interaction partners of Sorbs1 include c-Abl, Sos, flotillin, Grb4, ataxin-7, filamin C, among others. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212852 [Multi-domain] Cd Length: 55 Bit Score: 37.64 E-value: 2.53e-03

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....*.
gi 1804876928  786 KALYRFEARSHDEMSFNSGDII----QVDEKtigepgWLYGSFQGNFGWFPCNYVE 837
Cdd:cd11919      4 RAKFDFKAQTLKELPLQKGDIVyiykQIDQN------WYEGEHHGRVGIFPRSYIE 53

Third Src Homology 3 domain (SH3C) of CD2-associated protein; CD2AP, also called CMS (Cas ligand with Multiple SH3 domains) or METS1 (Mesenchyme-to-Epithelium Transition protein with SH3 domains), is a cytosolic adaptor protein that plays a role in regulating the cytoskeleton. It is critical in cell-to-cell union necessary for kidney function. It also stabilizes the contact between a T cell and antigen-presenting cells. It is primarily expressed in podocytes at the cytoplasmic face of the slit diaphragm and serves as a linker anchoring podocin and nephrin to the actin cytoskeleton. CD2AP contains three SH3 domains, a proline-rich region, and a C-terminal coiled-coil domain. All of these domains enable CD2AP to bind various protein partners and assemble complexes that have been implicated in many different functions. This alignment model represents the third SH3 domain (SH3C) of CD2AP. SH3C has been shown to bind ubiquitin. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212989 [Multi-domain] Cd Length: 57 Bit Score: 37.88 E-value: 2.55e-03

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....*
gi 1804876928 1077 EIAQVTSAYVASGSEQLSLAPGQLILILKKNS--SGWWQGELQARgkkrqKGWFP 1129
Cdd:cd12056      2 EYCKALFHYEGTNEDELDFKEGEIILIISKDTgePGWWKGELNGK-----EGVFP 51

Uncharacterized conserved protein, contains a C-terminal ATPase domain [Function unknown];

Pssm-ID: 443941 [Multi-domain] Cd Length: 1089 Bit Score: 42.59 E-value: 2.61e-03

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1804876928  572 EIKQLQQELQDYQNKLIYLVPEKQLLNERIKNMQ-LGNTPDLGIDLlhkKSLEKEelCQRLKEQLDALEKeTASKLSEMD 650
Cdd:COG4913    618 ELAELEEELAEAEERLEALEAELDALQERREALQrLAEYSWDEIDV---ASAERE--IAELEAELERLDA-SSDDLAALE 691

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1804876928  651 SfnnqlkcgnmddsvlqcllsllsclnnlflLLKELRESYNTQQLALEQLHKIKRDKLKEIERKRSELIQKKKLEDEAIR 730
Cdd:COG4913    692 E------------------------------QLEELEAELEELEEELDELKGEIGRLEKELEQAEEELDELQDRLEAAED 741

                          170       180       190       200       210       220       230
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 1804876928  731 KAKQGK----ENLWRESLRKE-EEEKQKRLQEE--KTQEKVQEEERKVEEkqcepasALVNYKALYRFEARSHD 797
Cdd:COG4913    742 LARLELrallEERFAAALGDAvERELRENLEERidALRARLNRAEEELER-------AMRAFNREWPAETADLD 808

Src homology 3 domain of Growth Arrest Specific protein 7; GAS7 is mainly expressed in the brain and is required for neurite outgrowth. It may also play a role in the protection and migration of embryonic stem cells. Treatment-related acute myeloid leukemia (AML) has been reported resulting from mixed-lineage leukemia (MLL)-GAS7 translocations as a complication of primary cancer treatment. GAS7 contains an N-terminal SH3 domain, followed by a WW domain, and a central F-BAR domain. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212763 [Multi-domain] Cd Length: 52 Bit Score: 37.49 E-value: 2.63e-03

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|
gi 1804876928 1009 ALYSYSSvEPGD--LTFIEGEEILVTQK-DGEWWTGSIGDRTGIFPSNYV 1055
Cdd:cd11829      4 TLYAFTG-EQHQqgLSFEAGELIRVLQApDGGWWEGEKDGLRGWFPASYV 52

Src homology 3 domain of CAS (Crk-Associated Substrate) scaffolding protein family member, Embryonal Fyn-associated Substrate; EFS is also called HEFS, CASS3 (Cas scaffolding protein family member 3) or SIN (Src-interacting protein). It was identified based on interactions with the Src kinases, Fyn and Yes. It plays a role in thymocyte development and acts as a negative regulator of T cell proliferation. CAS proteins function as molecular scaffolds to regulate protein complexes that are involved in many cellular processes. They share a common domain structure that includes an N-terminal SH3 domain, an unstructured substrate domain that contains many YxxP motifs, a serine-rich four-helix bundle, and a FAT-like C-terminal domain. The SH3 domain of CAS proteins binds to diverse partners including FAK, FRNK, Pyk2, PTP-PEST, DOCK180, among others. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212936 Cd Length: 62 Bit Score: 37.95 E-value: 2.64e-03

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|..
gi 1804876928 1009 ALYSYSSVEPGDLTFIEGEEILVTQKDGE----WWTGSIGDRTGIFPSNYVK 1056
Cdd:cd12003      5 ALYDNAAESPEELSFRRGDVLMVLKREHGslpgWWLCSLHGQQGIAPANRLR 56

First Src Homology 3 domain (SH3A) of CD2-associated protein; CD2AP, also called CMS (Cas ligand with Multiple SH3 domains) or METS1 (Mesenchyme-to-Epithelium Transition protein with SH3 domains), is a cytosolic adaptor protein that plays a role in regulating the cytoskeleton. It is critical in cell-to-cell union necessary for kidney function. It also stabilizes the contact between a T cell and antigen-presenting cells. It is primarily expressed in podocytes at the cytoplasmic face of the slit diaphragm and serves as a linker anchoring podocin and nephrin to the actin cytoskeleton. CD2AP contains three SH3 domains, a proline-rich region, and a C-terminal coiled-coil domain. All of these domains enable CD2AP to bind various protein partners and assemble complexes that have been implicated in many different functions. This alignment model represents the first SH3 domain (SH3A) of CD2AP. SH3A binds to the PXXXPR motif present in c-Cbl and the cytoplasmic domain of cell adhesion protein CD2. Its interaction with CD2 anchors CD2 at sites of cell contact. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212986 Cd Length: 56 Bit Score: 37.51 E-value: 2.66e-03

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|...
gi 1804876928 1006 EYIALYSYSSVEPGDLTFIEGEEILVTQKDGE--WWTGSIGDRTGIFPSNYVK 1056
Cdd:cd12053      1 EYIVEYDYDAVHEDELTIRVGEIIRNVKKLEEegWLEGELNGRRGMFPDNFVK 53

Src Homology 3 domain of Bruton's tyrosine kinase; BTK is a cytoplasmic (or nonreceptor) tyr kinase containing Src homology protein interaction domains (SH3, SH2) N-terminal to the catalytic tyr kinase domain. It also contains an N-terminal pleckstrin homology (PH) domain, which binds the products of PI3K and allows membrane recruitment and activation, and the Tec homology (TH) domain with proline-rich and zinc-binding regions. Btk is expressed in B-cells, and a variety of myeloid cells including mast cells, platelets, neutrophils, and dendrictic cells. It interacts with a variety of partners, from cytosolic proteins to nuclear transcription factors, suggesting a diversity of functions. Stimulation of a diverse array of cell surface receptors, including antigen engagement of the B-cell receptor (BCR), leads to PH-mediated membrane translocation of Btk and subsequent phosphorylation by Src kinase and activation. Btk plays an important role in the life cycle of B-cells including their development, differentiation, proliferation, survival, and apoptosis. Mutations in Btk cause the primary immunodeficiency disease, X-linked agammaglobulinaemia (XLA) in humans. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212839 [Multi-domain] Cd Length: 55 Bit Score: 37.50 E-value: 2.67e-03

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|
gi 1804876928 1008 IALYSYSSVEPGDLTFIEGEE-ILVTQKDGEWWTGSIGD-RTGIFPSNYV 1055
Cdd:cd11906      4 VALYDYTPMNAQDLQLRKGEEyVILEESNLPWWRARDKNgREGYIPSNYV 53

Third Src Homology 3 domain of SH3 domain containing ring finger 1, an E3 ubiquitin-protein ligase; SH3RF1 is also called POSH (Plenty of SH3s) or SH3MD2 (SH3 multiple domains protein 2). It is a scaffold protein that acts as an E3 ubiquitin-protein ligase. It plays a role in calcium homeostasis through the control of the ubiquitin domain protein Herp. It may also have a role in regulating death receptor mediated and JNK mediated apoptosis. SH3RF1 also enhances the ubiquitination of ROMK1 potassium channel resulting in its increased endocytosis. It contains an N-terminal RING finger domain and four SH3 domains. This model represents the third SH3 domain, located in the middle, of SH3RF1. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212859 [Multi-domain] Cd Length: 55 Bit Score: 37.64 E-value: 2.72e-03

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....*
gi 1804876928 1007 YIALYSYSSVEPGDLTFIEGEEILVTQK--DGeWWTGSI--GDRTGIFPSNYVKP 1057
Cdd:cd11926      2 YVAIYPYTPRKEDELELRKGEMFLVFERcqDG-WFKGTSmhTSKIGVFPGNYVAP 55

Centrosomal protein of 63 kDa; CEP63 is a family of eukaryotic proteins involved in centriole activity.

Pssm-ID: 465338 [Multi-domain] Cd Length: 264 Bit Score: 41.73 E-value: 2.88e-03

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1804876928  414 LEKRRQ--ALMEQQQREAERKAQKEKEEWERKQRELQEQEWKKQLELEKRLEKQRELERQREEERRKEIERREAAKQELE 491
Cdd:pfam17045   51 LERKHKeiGLLRQQLEELEKGKQELVAKYEQQLQKLQEELSKLKRSYEKLQRKQLKEAREEAKSREEDRSELSRLNGKLE 130

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1804876928  492 --RQRRLEWERirrqellnQRNREQEEIVRLNSKKKSLHLELEAL--NGKHQQISGRLQDVRLRKQTQKTEIEVLDKQCD 567
Cdd:pfam17045  131 efRQKSLEWEQ--------QRLQYQQQVASLEAQRKALAEQSSLIqsAAYQVQLEGRKQCLEASQSEIQRLRSKLERAQD 202

                          170       180       190       200       210       220       230
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|...
gi 1804876928  568 ------LEIMEIKQLQQELQDYQNKLIylvPEKQLLNERIKNMQLgntpdlgidLLHKKSLEKEELCQRLKEQ 634
Cdd:pfam17045  203 slcaqeLELERLRMRVSELGDSNRKLL---EEQQRLLEELRMSQR---------QLQVLQNELMELKATLQSQ 263

Uncharacterized conserved protein YhaN, contains AAA domain [Function unknown];

Pssm-ID: 443752 [Multi-domain] Cd Length: 641 Bit Score: 42.45 E-value: 2.94e-03

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1804876928  400 EDKRKANYERGNVELEKRRQALMEQQQ---REAERKAQKEKEEWERKQRELQeqewkkqlELEKRLEKQrelerqreeer 476
Cdd:COG4717    354 REAEELEEELQLEELEQEIAALLAEAGvedEEELRAALEQAEEYQELKEELE--------ELEEQLEEL----------- 414

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1804876928  477 rkeierREAAKQELERQRRLEWERiRRQELLNQRNREQEEIVRLNSKKKSLHLELEALngkhqQISGRLQDVRLRKQTQK 556
Cdd:COG4717    415 ------LGELEELLEALDEEELEE-ELEELEEELEELEEELEELREELAELEAELEQL-----EEDGELAELLQELEELK 482

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1804876928  557 TEIEVLDKQ---CDLEIMEIKQLQQELQD-YQNKLIYLVPE--KQLLNERIKNMQLGNTPDLGIDLLHKKSLEKEELCQR 630
Cdd:COG4717    483 AELRELAEEwaaLKLALELLEEAREEYREeRLPPVLERASEyfSRLTDGRYRLIRIDEDLSLKVDTEDGRTRPVEELSRG 562


                   ....*
gi 1804876928  631 LKEQL 635
Cdd:COG4717    563 TREQL 567

cell envelope integrity inner membrane protein TolA; Provisional

Pssm-ID: 236545 [Multi-domain] Cd Length: 387 Bit Score: 42.10 E-value: 2.97e-03

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1804876928  403 RKANYERGNVELEKRRQALMEQQQREAERKAQKEKEEW-ERKQRELQEQEWKKQLELEKRLEKQRelerQREEERRKEIE 481
Cdd:PRK09510    66 RQQQQQKSAKRAEEQRKKKEQQQAEELQQKQAAEQERLkQLEKERLAAQEQKKQAEEAAKQAALK----QKQAEEAAAKA 141

                           90
                   ....*....|....*.
gi 1804876928  482 RREAAKQELERQRRLE 497
Cdd:PRK09510   142 AAAAKAKAEAEAKRAA 157

Src homology 3 domain of SH3 and multiple ankyrin repeat domains protein 3; Shank3, also called ProSAP2 (Proline-rich synapse-associated protein 2), is widely expressed. It plays a role in the formation of dendritic spines and synapses. Haploinsufficiency of the Shank3 gene causes the 22q13 deletion/Phelan-McDermid syndrome, and variants of Shank3 have been implicated in autism spectrum disorder, schizophrenia, and intellectual disability. Shank proteins carry scaffolding functions through multiple sites of protein-protein interaction in its domain architecture, including ankyrin (ANK) repeats, a long proline rich region, as well as SH3, PDZ, and SAM domains. The SH3 domain of Shank binds GRIP, a scaffold protein that binds AMPA receptors and Eph receptors/ligands. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212917 Cd Length: 52 Bit Score: 37.24 E-value: 3.02e-03

                           10        20        30        40
                   ....*....|....*....|....*....|....*....|....*....
gi 1804876928 1154 IAMYDYVANNEDELNFSKGQLINVLNKDDPDWWQGEINGVTGLFPSNYV 1202
Cdd:cd11984      4 IAVKAYSPQGEGEIQLNRGERVKVLSIGEGGFWEGTVKGRTGWFPADCV 52

Src homology 3 domain of Brk (Breast tumor kinase) Protein Tyrosine Kinase (PTK), also called PTK6; Brk is a cytoplasmic (or non-receptor) PTK with limited homology to Src kinases. It has been found to be overexpressed in a majority of breast tumors. It plays roles in normal cell differentiation, proliferation, survival, migration, and cell cycle progression. Brk substrates include RNA-binding proteins (SLM-1/2, Sam68), transcription factors (STAT3/5), and signaling molecules (Akt, paxillin, IRS-4). Src kinases in general contain an N-terminal SH4 domain with a myristoylation site, followed by SH3 and SH2 domains, a tyr kinase domain, and a regulatory C-terminal region containing a conserved tyr; they are activated by autophosphorylation at the tyr kinase domain, but are negatively regulated by phosphorylation at the C-terminal tyr by Csk (C-terminal Src Kinase). However, Brk lacks the N-terminal myristoylation site. The SH3 domain of Src kinases contributes to substrate recruitment by binding adaptor proteins/substrates, and regulation of kinase activity through an intramolecular interaction. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212781 [Multi-domain] Cd Length: 58 Bit Score: 37.54 E-value: 3.04e-03

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....*
gi 1804876928 1154 IAMYDYVANNEDELNFSKGQLINVLNKDDpDWW----QGEINGVT--GLFPSNYV 1202
Cdd:cd11847      3 KALWDFKARGDEELSFQAGDQFRIAERSG-DWWtalkLDRAGGVVaqGFVPNNYL 56

Third Src Homology 3 domain (SH3C) of CD2-associated protein; CD2AP, also called CMS (Cas ligand with Multiple SH3 domains) or METS1 (Mesenchyme-to-Epithelium Transition protein with SH3 domains), is a cytosolic adaptor protein that plays a role in regulating the cytoskeleton. It is critical in cell-to-cell union necessary for kidney function. It also stabilizes the contact between a T cell and antigen-presenting cells. It is primarily expressed in podocytes at the cytoplasmic face of the slit diaphragm and serves as a linker anchoring podocin and nephrin to the actin cytoskeleton. CD2AP contains three SH3 domains, a proline-rich region, and a C-terminal coiled-coil domain. All of these domains enable CD2AP to bind various protein partners and assemble complexes that have been implicated in many different functions. This alignment model represents the third SH3 domain (SH3C) of CD2AP. SH3C has been shown to bind ubiquitin. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212989 [Multi-domain] Cd Length: 57 Bit Score: 37.50 E-value: 3.11e-03

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|...
gi 1804876928  925 QALCSWTAKKDNHLNFSKHDIITVLEQ---QENWWFGEVHGGRGWFPKSYVKI 974
Cdd:cd12056      5 KALFHYEGTNEDELDFKEGEIILIISKdtgEPGWWKGELNGKEGVFPDNFVSQ 57

N-terminal domain of Kruppel-like factor 3; Kruppel-like factor 3 (KLF3; also called Krueppel-like factor 3 and originally called Basic Kruppel-like Factor/BKLF), was the third member of the KLF family of zinc finger transcription factors to be discovered. KLF3 possesses a wide range of biological impacts on regulating apoptosis, differentiation, and proliferation in various tissues during the entire progression process. It has been proposed as a tumor suppressor in colorectal cancer. It appears to function predominantly as a repressor of transcription, turning genes off by recruiting the C-terminal Binding Protein co-repressors CtBP1 and CtBP2. CtBP docks onto a short motif (residues 61-65) in the N-terminus of KLF3, through the Proline-X-Aspartate-Leucine-Serine (PXDLS) motif. CtBP in turn recruits histone modifying enzymes to alter chromatin and repress gene expression. KLF3 belongs to a family of proteins, called the Specificity Protein (SP)/KLF family, characterized by a C-terminal DNA-binding domain of 81 amino acids consisting of three Kruppel-like C2H2 zinc fingers. These factors bind to a loose consensus motif, namely NNRCRCCYY (where N is any nucleotide; R is A/G, and Y is C/T), such as the recurring motifs in GC and GT boxes (5'-GGGGCGGGG-3' and 5-GGTGTGGGG-3') that are present in promoters and more distal regulatory elements of mammalian genes. Members of the KLF family can act as activators or repressors of transcription depending on cell and promoter context. KLFs regulate various cellular functions, such as proliferation, differentiation, and apoptosis, as well as the development and homeostasis of several types of tissue. In addition to the C-terminal DNA-binding domain, each KLF also has a unique N-terminal activation/repression domain that confers specificity and allows it to bind specifically to a certain partner, leading to distinct activities in vivo. This model represents the N-terminal domain of KLF3.

Pssm-ID: 410554 [Multi-domain] Cd Length: 214 Bit Score: 40.79 E-value: 3.30e-03

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1804876928  140 PPMFSPLISARFGMGSMPNLSIPHSLPPVAPMATPLssatsgtTLPPLMMPAPLVPSVSTSSLPNGTAGLIQPLSIPYSS 219
Cdd:cd21577     42 SSSSSSSPSSRASPPSPYSKSSPPSPPQQRPLSPPL-------SLPPPVAPPPLSPGSVPGGLPVISPVMVQPVPVLYPP 114


                   ....*..
gi 1804876928  220 STLPHTS 226
Cdd:cd21577    115 HLHQPIM 121

Src homology 3 domain of High osmolarity signaling protein Sho1p; Sho1p (or Sho1), also called SSU81 (Suppressor of SUA8-1 mutation), is a yeast membrane protein that regulates adaptation to high salt conditions by activating the HOG (high-osmolarity glycerol) pathway. High salt concentrations lead to the localization to the membrane of the MAPKK Pbs2, which is then activated by the MAPKK Ste11 and in turn, activates the MAPK Hog1. Pbs2 is localized to the membrane though the interaction of its PxxP motif with the SH3 domain of Sho1p. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212789 [Multi-domain] Cd Length: 55 Bit Score: 37.40 E-value: 3.32e-03

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....*
gi 1804876928  923 KAQALCSWTAKKD--NHLNFSKHDIITVLEQQENWWFGEVHGGR-GWFPKSYVKI 974
Cdd:cd11855      1 RARALYPYDASPDdpNELSFEKGEILEVSDTSGKWWQARKSNGEtGICPSNYLQL 55

Fourth N-terminal Src homology 3 domain of Dynamin Binding Protein, also called Tuba; DNMBP or Tuba is a cdc42-specific guanine nucleotide exchange factor (GEF) that contains four N-terminal SH3 domains, a central RhoGEF [or Dbl homology (DH)] domain followed by a Bin/Amphiphysin/Rvs (BAR) domain, and two C-terminal SH3 domains. It provides a functional link between dynamin and key regulatory proteins of the actin cytoskeleton. It plays an important role in regulating cell junction configuration. The four N-terminal SH3 domains of DNMBP bind the GTPase dynamin, which plays an important role in the fission of endocytic vesicles. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212731 Cd Length: 50 Bit Score: 37.02 E-value: 3.34e-03

                           10        20        30        40
                   ....*....|....*....|....*....|....*....|....*....
gi 1804876928 1153 VIAMYDYVANNEDELNFSKGQLINVLNKDDPDWWQGEINGVTGLFPSNY 1201
Cdd:cd11797      2 GVALYRFQALEPNELDFEVGDRIRIIATLEDGWLEGELKGRRGIFPHRF 50

Chromatin assembly factor 1 complex p150 subunit, N-terminal; CAF-1_p150 is a polypeptide subunit of CAF-1, which functions in depositing newly synthesized and acetylated histones H3/H4 into chromatin during DNA replication and repair. CAF-1_p150 includes the HP1 interaction site, the PEST, KER and ED interacting sites. CAF-1_p150 interacts directly with newly synthesized and acetylated histones through the acidic KER and ED domains. The PEST domain is associated with proteins that undergo rapid proteolysis.

Pssm-ID: 402959 [Multi-domain] Cd Length: 164 Bit Score: 40.06 E-value: 3.38e-03

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1804876928  387 QEEEPQKKLpvtfEDKRKANYERGNVELEKRRQAlmEQQQREAERKAQKEKEEWER--KQRELQEQEWKKQLELEKRLEK 464
Cdd:pfam11600   33 AEKEEKERL----KEEAKAEKERAKEEARRKKEE--EKELKEKERREKKEKDEKEKaeKLRLKEEKRKEKQEALEAKLEE 106


                   .
gi 1804876928  465 Q 465
Cdd:pfam11600  107 K 107

Src homology 3 domain of the Rho guanine nucleotide exchange factor ARHGEF9; ARHGEF9, also called PEM2 or collybistin, selectively activates Cdc42 by exchanging bound GDP for free GTP. It is highly expressed in the brain and it interacts with gephyrin, a postsynaptic protein associated with GABA and glycine receptors. Mutations in the ARHGEF9 gene cause X-linked mental retardation with associated features like seizures, hyper-anxiety, aggressive behavior, and sensory hyperarousal. ARHGEF9 contains a SH3 domain followed by RhoGEF (also called Dbl-homologous or DH) and Pleckstrin Homology (PH) domains. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212908 Cd Length: 62 Bit Score: 37.77 E-value: 3.40e-03

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....*..
gi 1804876928 1079 AQVTSAYVASGSEQLSLAPGQLILILKKNSSGWWQGELQargkkRQKGWFPASHVKL 1135
Cdd:cd11975      7 AEAVWDHVTMANRELAFKAGDVIKVLDASNKDWWWGQID-----DEEGWFPASFVRL 58

Third Src homology 3 domain of Tyrosine kinase substrate (Tks) proteins; Tks proteins are Src substrates and scaffolding proteins that play important roles in the formation of podosomes and invadopodia, the dynamic actin-rich structures that are related to cell migration and cancer cell invasion. Vertebrates contain two Tks proteins, Tks4 (Tyr kinase substrate with four SH3 domains) and Tks5 (Tyr kinase substrate with five SH3 domains), which display partially overlapping but non-redundant functions. Both associate with the ADAMs family of transmembrane metalloproteases, which function as sheddases and mediators of cell and matrix interactions. Tks5 interacts with N-WASP and Nck, while Tks4 is essential for the localization of MT1-MMP (membrane-type 1 matrix metalloproteinase) to invadopodia. Tks proteins contain an N-terminal Phox homology (PX) domain and four or five SH3 domains. This model characterizes the third SH3 domain of Tks proteins. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212950 Cd Length: 53 Bit Score: 37.43 E-value: 3.40e-03

                           10        20        30        40
                   ....*....|....*....|....*....|....*....|....*..
gi 1804876928 1087 ASGSEQLSLAPGQLILILKKNSSGWWQGELQArgkkrQKGWFPASHV 1133
Cdd:cd12017     10 ATIQDGISFQKGQKVEVIDKNPSGWWYVKIDG-----KEGWAPSSYI 51

Src homology 3 domain of CAS (Crk-Associated Substrate) scaffolding protein family member 4; CASS4, also called HEPL (HEF1-EFS-p130Cas-like), localizes to focal adhesions and plays a role in regulating FAK activity, focal adhesion integrity, and cell spreading. It is most abundant in blood cells and lung tissue, and is also found in high levels in leukemia and ovarian cell lines. CAS proteins function as molecular scaffolds to regulate protein complexes that are involved in many cellular processes. They share a common domain structure that includes an N-terminal SH3 domain, an unstructured substrate domain that contains many YxxP motifs, a serine-rich four-helix bundle, and a FAT-like C-terminal domain. The SH3 domain of CAS proteins binds to diverse partners including FAK, FRNK, Pyk2, PTP-PEST, DOCK180, among others. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212933 Cd Length: 57 Bit Score: 37.55 E-value: 3.47e-03

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|
gi 1804876928  786 KALYRFEARSHDEMSFNSGDIIQVDEKTI-GEPGWLYGSFQGNFGWFPCN 834
Cdd:cd12000      4 RALYDNKADCSDELAFRRGDILTVLEQNVpGSEGWWKCLLHGRQGLAPAN 53

Src homology 3 domain of ArfGAP with SH3 domain, ankyrin repeat and PH domain containing protein 2; ASAP2 is also called DDEF2 (Development and Differentiation Enhancing Factor 2), AMAP2, centaurin beta-3, or PAG3. It mediates the functions of Arf GTPases vial dual mechanisms: it exhibits GTPase activating protein (GAP) activity towards class I (Arf1) and II (Arf5) Arfs; and it binds class III Arfs (GTP-Arf6) stably without GAP activity. It binds paxillin and is implicated in Fcgamma receptor-mediated phagocytosis in macrophages and in cell migration. ASAP2 contains an N-terminal BAR domain, followed by a Pleckstrin homology (PH) domain, an Arf GAP domain, ankyrin (ANK) repeats, and a C-terminal SH3 domain. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212899 Cd Length: 56 Bit Score: 37.24 E-value: 3.50e-03

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....
gi 1804876928  923 KAQALCSWTAKKDNHLNFSKHDIITV-LEQQENWWFGEVHGG---RGWFPKSYV 972
Cdd:cd11966      1 RVKALYNCVADNPDELTFSEGEIIIVdGEEDKEWWIGHIDGEptrRGAFPVSFV 54

Src Homology 3 domain of Cytokinesis protein 3 and similar proteins; Cytokinesis protein 3 (Cyk3 or Cyk3p) is a component of the actomyosin ring independent cytokinesis pathway in yeast. It interacts with Inn1 and facilitates its recruitment to the bud neck, thereby promoting cytokinesis. Cyk3p contains an N-terminal SH3 domain and a C-terminal transglutaminase-like domain. The Cyk3p SH3 domain binds to the C-terminal proline-rich region of Inn1. SH3 domains bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs; they play a role in the regulation of enzymes by intramolecular interactions, changing the subcellular localization of signal pathway components and mediate multiprotein complex assemblies.

Pssm-ID: 212822 Cd Length: 53 Bit Score: 37.09 E-value: 3.53e-03

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|...
gi 1804876928  923 KAQALCSWTAKKDNHLNFSKHDIITVLE-QQENWWFGEV--HGGRGWFPKSYV 972
Cdd:cd11889      1 KVKAVYSWAGETEGDLGFLEGDLIEVLSiGDGSWWSGKLrrNGAEGIFPSNFV 53

Synaptonemal complex protein 1 (SCP-1); Synaptonemal complex protein 1 (SCP-1) is the major component of the transverse filaments of the synaptonemal complex. Synaptonemal complexes are structures that are formed between homologous chromosomes during meiotic prophase.

Pssm-ID: 114219 [Multi-domain] Cd Length: 787 Bit Score: 42.02 E-value: 3.64e-03

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1804876928  421 LMEQQQREAERKAQKEKEEWERKQ----------------RELQEQEWKKQLELEKRLEKQRELERQREEERRKEIERRE 484
Cdd:pfam05483  160 LKETCARSAEKTKKYEYEREETRQvymdlnnniekmilafEELRVQAENARLEMHFKLKEDHEKIQHLEEEYKKEINDKE 239

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1804876928  485 AAK-----QELERQRR-------LEWERIRRQELLNQRNREQEEIVRLNSKKKSLHLELEALNGKHQQ-ISGRL---QDV 548
Cdd:pfam05483  240 KQVsllliQITEKENKmkdltflLEESRDKANQLEEKTKLQDENLKELIEKKDHLTKELEDIKMSLQRsMSTQKaleEDL 319

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1804876928  549 RLRKQT-------QKTEIEVLDKQ---------------CDLEIMeIKQLQQELQDYQNKLIYLVPEKQLLNERIKNM-Q 605
Cdd:pfam05483  320 QIATKTicqlteeKEAQMEELNKAkaahsfvvtefeattCSLEEL-LRTEQQRLEKNEDQLKIITMELQKKSSELEEMtK 398

                          250       260       270       280       290       300       310       320
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1804876928  606 LGNTPDLGIDLLHKKSLEKEELCQRlKEQLDALEKETASKLSEMdSFNNQLKCGNMDDSVLQCLLSLLSCLNnlflLLKE 685
Cdd:pfam05483  399 FKNNKEVELEELKKILAEDEKLLDE-KKQFEKIAEELKGKEQEL-IFLLQAREKEIHDLEIQLTAIKTSEEH----YLKE 472

                          330       340       350       360       370       380       390       400
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1804876928  686 LRESynTQQLALEQLHKIK----RDKL----KEIERKRSELIQKKKLEDEAIRKAKQGKENLWRESLRKEEEEKQKRLQE 757
Cdd:pfam05483  473 VEDL--KTELEKEKLKNIEltahCDKLllenKELTQEASDMTLELKKHQEDIINCKKQEERMLKQIENLEEKEMNLRDEL 550

                          410       420       430       440
                   ....*....|....*....|....*....|....*....|....*...
gi 1804876928  758 EKTQE--KVQEEERKVEEKQCEPASALVNYKALYRFEARSHDEMSFNS 803
Cdd:pfam05483  551 ESVREefIQKGDEVKCKLDKSEENARSIEYEVLKKEKQMKILENKCNN 598

Src homology 3 domain of the Rho guanine nucleotide exchange factor, ephexin-1 (also called NGEF or ARHGEF27); Ephexin-1, also called NGEF (neuronal GEF) or ARHGEF27, activates RhoA, Tac1, and Cdc42 by exchanging bound GDP for free GTP. It is expressed mainly in the brain in a region associated with movement control. It regulates the stability of postsynaptic acetylcholine receptor (AChR) clusters and thus, plays a critical role in the maturation and neurotransmission of neuromuscular junctions. Ephexin-1 directly interacts with the ephrin receptor EphA4 and their coexpression enhances the ability of ephexin-1 to activate RhoA. It is required for normal axon growth and EphA-induced growth cone collapse. Ephexin-1 contains RhoGEF (also called Dbl-homologous or DH), Pleckstrin Homology (PH), and SH3 domains. The SH3 domains of ARHGEFs play an autoinhibitory role through intramolecular interactions with a proline-rich region N-terminal to the DH domain. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212872 [Multi-domain] Cd Length: 55 Bit Score: 37.23 E-value: 3.65e-03

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....
gi 1804876928 1152 QVIAMYDYVANNEDELNFSKGQLINVLNKDDPDWWQGEI--NGVTGLFPSNYVK 1203
Cdd:cd11939      1 QVQCVHPYVSQEPDELSLELADVLNILDKTDDGWIFGERlhDQERGWFPSSVVE 54

Third (or C-terminal) Src Homology 3 domain of Sorbin and SH3 domain containing 2 (Sorbs2), also called Arg-binding protein 2 (ArgBP2); Sorbs2 or ArgBP2 is an adaptor protein containing one sorbin homology (SoHo) and three SH3 domains. It regulates actin-dependent processes including cell adhesion, morphology, and migration. It is expressed in many tissues and is abundant in the heart. Like vinexin, it is found in focal adhesion where it interacts with vinculin and afadin. It also localizes in epithelial cell stress fibers and in cardiac muscle cell Z-discs. Sorbs2 has been implicated to play roles in the signaling of c-Arg, Akt, and Pyk2. Other interaction partners of Sorbs2 include c-Abl, flotillin, spectrin, dynamin 1/2, synaptojanin, PTP-PEST, among others. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212850 [Multi-domain] Cd Length: 61 Bit Score: 37.28 E-value: 3.69e-03

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....*....
gi 1804876928 1002 TVGDEYIALYSYSSVEPGDLTFIEGEEILVTQK-DGEWWTGSiGDRT---GIFPSNYVK 1056
Cdd:cd11917      2 GGGEPFQALYNYMPRNEDELELREGDVIDVMEKcDDGWFVGT-SRRTkffGTFPGNYVK 59

Src homology 3 domain of eumetazoan Actin-binding protein 1; Abp1, also called drebrin-like protein, is an adaptor protein that functions in receptor-mediated endocytosis and vesicle trafficking. It contains an N-terminal actin-binding module, the actin-depolymerizing factor (ADF) homology domain, a helical domain, and a C-terminal SH3 domain. Mammalian Abp1, unlike yeast Abp1, does not contain an acidic domain that interacts with the Arp2/3 complex. It regulates actin dynamics indirectly by interacting with dynamin and WASP family proteins. Abp1 deficiency causes abnormal organ structure and function of the spleen, heart, and lung of mice. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212893 [Multi-domain] Cd Length: 54 Bit Score: 36.99 E-value: 3.73e-03

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|.
gi 1804876928 1085 YVASGSEQLSLAPGQLILILKKNSSGWWQGelqaRGKKRQKGWFPASHVKL 1135
Cdd:cd11960      8 YQAADDTEISFDPGDIITDIEQIDEGWWRG----TGPDGTYGLFPANYVEL 54

Src Homology 3 domain of the p40phox subunit of NADPH oxidase; p40phox, also called Neutrophil cytosol factor 4 (NCF-4), is a cytosolic subunit of the phagocytic NADPH oxidase complex (also called Nox2 or gp91phox) which plays a crucial role in the cellular response to bacterial infection. NADPH oxidase catalyzes the transfer of electrons from NADPH to oxygen during phagocytosis forming superoxide and reactive oxygen species. p40phox positively regulates NADPH oxidase in both phosphatidylinositol-3-phosphate (PI3P)-dependent and PI3P-independent manner. It contains an N-terminal PX domain, a central SH3 domain, and a C-terminal PB1 domain that interacts with p67phox. The SH3 domain of p40phox binds to canonical polyproline and noncanonical motifs at the C-terminus of p47phox. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212802 Cd Length: 54 Bit Score: 37.09 E-value: 3.82e-03

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....
gi 1804876928  923 KAQALCSWTAKKDNHLNFSKHDIITVLEQ-QENWWFGEVHGGRGWFPKSYVKII 975
Cdd:cd11869      1 RAEALFDFTGNSKLELNFKAGDVIFLLSRvNKDWLEGTVRGATGIFPLSFVKII 54

First or N-terminal Src homology 3 domain of the p47phox subunit of NADPH oxidase, also called Neutrophil Cytosolic Factor 1; p47phox, or NCF1, is a cytosolic subunit of the phagocytic NADPH oxidase complex (also called Nox2 or gp91phox), which plays a key role in the ability of phagocytes to defend against bacterial infections. NADPH oxidase catalyzes the transfer of electrons from NADPH to oxygen during phagocytosis forming superoxide and reactive oxygen species. p47phox is required for activation of NADH oxidase and plays a role in translocation. It contains an N-terminal Phox homology (PX) domain, tandem SH3 domains (N-SH3 and C-SH3), a polybasic/autoinhibitory region, and a C-terminal proline-rich region (PRR). This model characterizes the first SH3 domain (or N-SH3) of p47phox. In its inactive state, the tandem SH3 domains interact intramolecularly with the autoinhibitory region; upon activation, the tandem SH3 domains are exposed through a conformational change, resulting in their binding to the PRR of p22phox and the activation of NADPH oxidase. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212954 [Multi-domain] Cd Length: 53 Bit Score: 36.86 E-value: 4.19e-03

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|
gi 1804876928  925 QALCSWTAKKDNHLNFSKHDIITVLEQQEN-WWFGEVHGGRGWFPKSYVK 973
Cdd:cd12021      3 RAIADYEKSSKSEMALKTGDVVEVVEKSENgWWFCQLKAKRGWVPASYLE 52

Src homology 3 domain of CAS (Crk-Associated Substrate) scaffolding proteins; CAS proteins function as molecular scaffolds to regulate protein complexes that are involved in many cellular processes including migration, chemotaxis, apoptosis, differentiation, and progenitor cell function. They mediate the signaling of integrins at focal adhesions where they localize, and thus, regulate cell invasion and survival. Over-expression of these proteins is implicated in poor prognosis, increased metastasis, and resistance to chemotherapeutics in many cancers such as breast, lung, melanoma, and glioblastoma. CAS proteins have also been linked to the pathogenesis of inflammatory disorders, Alzheimer's, Parkinson's, and developmental defects. They share a common domain structure that includes an N-terminal SH3 domain, an unstructured substrate domain that contains many YxxP motifs, a serine-rich four-helix bundle, and a FAT-like C-terminal domain. Vertebrates contain four CAS proteins: BCAR1 (or p130Cas), NEDD9 (or HEF1), EFS (or SIN), and CASS4 (or HEPL). The SH3 domain of CAS proteins binds to diverse partners including FAK, FRNK, Pyk2, PTP-PEST, DOCK180, among others. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212778 Cd Length: 56 Bit Score: 36.94 E-value: 4.54e-03

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|...
gi 1804876928  786 KALYRFEARSHDEMSFNSGDIIQVDEK-TIGEPGWLYGSFQGNFGWFPCNYVE 837
Cdd:cd11844      3 RALYDNVAESPDELAFRRGDILTVLEQnTAGLEGWWLCSLRGRQGIAPGNRLK 55

Laminin Domain I; coiled-coil structure. It has been suggested that the domains I and II from laminin A, B1 and B2 may come together to form a triple helical coiled-coil structure.

Pssm-ID: 310534 [Multi-domain] Cd Length: 258 Bit Score: 40.86 E-value: 4.62e-03

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1804876928  503 RQELLNQRNREQEEIVRLNSKKK---SLHLELEALNGKHQQISGRLQDVRLRKQTQKTEIEVLDkqcdleiMEIKQLQQE 579
Cdd:pfam06008   25 TKQLQEYLSPENAHKIQIEILEKelsSLAQETEELQKKATQTLAKAQQVNAESERTLGHAKELA-------EAIKNLIDN 97

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1804876928  580 LQDYQNKLIYL------VPEKQLLNE-----------RIKN---MQLGNTPDL--GIDLLHkkslEKEELCQRLKEQLDA 637
Cdd:pfam06008   98 IKEINEKVATLgendfaLPSSDLSRMlaeaqrmlgeiRSRDfgtQLQNAEAELkaAQDLLS----RIQTWFQSPQEENKA 173

                          170       180
                   ....*....|....*....|
gi 1804876928  638 LEKETASKLSEmdsFNNQLK 657
Cdd:pfam06008  174 LANALRDSLAE---YEAKLS 190

Chromosome segregation ATPase Smc [Cell cycle control, cell division, chromosome partitioning];

Pssm-ID: 440809 [Multi-domain] Cd Length: 983 Bit Score: 41.85 E-value: 4.67e-03

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1804876928  392 QKKLPVTFEDKRKANYERGNVELEKRRQALMEQQQREAERKAQKEKEEWERKQRELQEQEwkkQLELEKRLEKQRELERQ 471
Cdd:COG1196    584 ARAALAAALARGAIGAAVDLVASDLREADARYYVLGDTLLGRTLVAARLEAALRRAVTLA---GRLREVTLEGEGGSAGG 660

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1804876928  472 REEERRKEIERREAAKQELERQRRLEWERIRRQELLNQRNREQEEIVRLNSKKKSLHLELEALNGKHQQISGRLQDVRLR 551
Cdd:COG1196    661 SLTGGSRRELLAALLEAEAELEELAERLAEEELELEEALLAEEEEERELAEAEEERLEEELEEEALEEQLEAEREELLEE 740

                          170       180       190
                   ....*....|....*....|....*....|....*.
gi 1804876928  552 KQTQKTEIEVLDKQCDLEIMEIKQLQQELQDYQNKL 587
Cdd:COG1196    741 LLEEEELLEEEALEELPEPPDLEELERELERLEREI 776

TolA protein; TolA couples the inner membrane complex of itself with TolQ and TolR to the outer membrane complex of TolB and OprL (also called Pal). Most of the length of the protein consists of low-complexity sequence that may differ in both length and composition from one species to another, complicating efforts to discriminate TolA (the most divergent gene in the tol-pal system) from paralogs such as TonB. Selection of members of the seed alignment and criteria for setting scoring cutoffs are based largely conserved operon struction. //The Tol-Pal complex is required for maintaining outer membrane integrity. Also involved in transport (uptake) of colicins and filamentous DNA, and implicated in pathogenesis. Transport is energized by the proton motive force. TolA is an inner membrane protein that interacts with periplasmic TolB and with outer membrane porins ompC, phoE and lamB. [Transport and binding proteins, Other, Cellular processes, Pathogenesis]

Pssm-ID: 274303 [Multi-domain] Cd Length: 346 Bit Score: 41.37 E-value: 4.74e-03

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1804876928  683 LKELRESYNTQQLA--LEQLHKIKRDKLKEIE--RKRSELIQKKKLEDEAIRKAKQgkenlwrESLRKEEEEKQKRLQEE 758
Cdd:TIGR02794   91 QKELEQRAAAEKAAkqAEQAAKQAEEKQKQAEeaKAKQAAEAKAKAEAEAERKAKE-------EAAKQAEEEAKAKAAAE 163

                           90
                   ....*....|....*.
gi 1804876928  759 KtQEKVQEEERKVEEK 774
Cdd:TIGR02794  164 A-KKKAEEAKKKAEAE 178

Chromosome condensin MukBEF, ATPase and DNA-binding subunit MukB [Cell cycle control, cell division, chromosome partitioning];

Pssm-ID: 442330 [Multi-domain] Cd Length: 1470 Bit Score: 41.86 E-value: 4.75e-03

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1804876928  500 RIRRQELLNQRNREQEEIVRLNSKKKSLHLELEALNGKHQQISgrlqdvRLRKQTQKTEIEVLDKQCDleimEIKQLQQE 579
Cdd:COG3096    842 RQRRSELERELAQHRAQEQQLRQQLDQLKEQLQLLNKLLPQAN------LLADETLADRLEELREELD----AAQEAQAF 911

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1804876928  580 LQDYQNKLIYLVPEKQLLneriknmqlgNTPDLGIDLLHKKSLEKEELCQRLKEQLDALE-----------KETASKLSE 648
Cdd:COG3096    912 IQQHGKALAQLEPLVAVL----------QSDPEQFEQLQADYLQAKEQQRRLKQQIFALSevvqrrphfsyEDAVGLLGE 981

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1804876928  649 MDSFNNQLKcgnmddsvlQCLLSLLSCLNNLFLLLKELRESYN--TQQLA-LEQLHKIKRDKLKEIERKRSEL-IQkkkL 724
Cdd:COG3096    982 NSDLNEKLR---------ARLEQAEEARREAREQLRQAQAQYSqyNQVLAsLKSSRDAKQQTLQELEQELEELgVQ---A 1049

                          250       260       270       280       290       300       310       320
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1804876928  725 EDEAIRKAKQGKENLWRE----SLRKEEEEKQKRLQE---EKTQEKVQEEERKVEEKQCEPASALVNYKALYRFeARSHD 797
Cdd:COG3096   1050 DAEAEERARIRRDELHEElsqnRSRRSQLEKQLTRCEaemDSLQKRLRKAERDYKQEREQVVQAKAGWCAVLRL-ARDND 1128

C-terminal (Fourth) Src Homology 3 domain of SH3 domain containing ring finger 1 (SH3RF1), SH3RF3, and similar domains; SH3RF1 (or POSH) and SH3RF3 (or POSH2) are scaffold proteins that function as E3 ubiquitin-protein ligases. They contain an N-terminal RING finger domain and four SH3 domains. This model represents the fourth SH3 domain, located at the C-terminus of SH3RF1 and SH3RF3, and similar domains. SH3RF1 plays a role in calcium homeostasis through the control of the ubiquitin domain protein Herp. It may also have a role in regulating death receptor mediated and JNK mediated apoptosis. SH3RF3 interacts with p21-activated kinase 2 (PAK2) and GTP-loaded Rac1. It may play a role in regulating JNK mediated apoptosis in certain conditions. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212719 Cd Length: 55 Bit Score: 37.06 E-value: 4.76e-03

                           10        20        30        40
                   ....*....|....*....|....*....|....*....|....*..
gi 1804876928 1159 YVANNEDELNFSKGQLINVLNKDDPDWWQGEI--NGVTGLFPSNYVK 1203
Cdd:cd11785      8 YPPQSEAELELKEGDIVFVHKKREDGWFKGTLqrTGKTGLFPGSFVE 54

Second Src Homology 3 domain of SH3 domain containing ring finger proteins; This model represents the second SH3 domain of SH3RF1 (or POSH), SH3RF2 (or POSHER), SH3RF3 (POSH2), and similar domains. Members of this family are scaffold proteins that function as E3 ubiquitin-protein ligases. They all contain an N-terminal RING finger domain and multiple SH3 domains; SH3RF1 and SH3RF3 have four SH3 domains while SH3RF2 has three. SH3RF1 plays a role in calcium homeostasis through the control of the ubiquitin domain protein Herp. It may also have a role in regulating death receptor mediated and JNK mediated apoptosis. SH3RF3 interacts with p21-activated kinase 2 (PAK2) and GTP-loaded Rac1. It may play a role in regulating JNK mediated apoptosis in certain conditions. SH3RF2 acts as an anti-apoptotic regulator of the JNK pathway by binding to and promoting the degradation of SH3RF1. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212721 [Multi-domain] Cd Length: 53 Bit Score: 36.93 E-value: 4.77e-03

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....*..
gi 1804876928  786 KALYRFEARSHDE---MSFNSGDIIQV----DEKtigepgWLYGSFQGNFGWFPCNY 835
Cdd:cd11787      3 KALYDFEMKDEDEkdcLTFKKGDVITVirrvDEN------WAEGRLGDKIGIFPISF 53

Src homology 3 domain of Cortactin; Cortactin was originally identified as a substrate of Src kinase. It is an actin regulatory protein that binds to the Arp2/3 complex and stabilizes branched actin filaments. It is involved in cellular processes that affect cell motility, adhesion, migration, endocytosis, and invasion. It is expressed ubiquitously except in hematopoietic cells, where the homolog hematopoietic lineage cell-specific 1 (HS1) is expressed instead. Cortactin contains an N-terminal acidic domain, several copies of a repeat domain found in cortactin and HS1, a proline-rich region, and a C-terminal SH3 domain. The N-terminal region interacts with the Arp2/3 complex and F-actin, and is crucial in regulating branched actin assembly. Cortactin also serves as a scaffold and provides a bridge to the actin cytoskeleton for membrane trafficking and signaling proteins that bind to its SH3 domain. Binding partners for the SH3 domain of cortactin include dynamin2, N-WASp, MIM, FGD1, among others. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212892 [Multi-domain] Cd Length: 53 Bit Score: 37.01 E-value: 4.77e-03

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|.
gi 1804876928 1085 YVASGSEQLSLAPGQLILILKKNSSGWWQGElqARGkkrQKGWFPASHVKL 1135
Cdd:cd11959      8 YQAADDDEISFDPDDIITNIEMIDEGWWRGV--CRG---KYGLFPANYVEL 53

Src homology 3 domain of SH3 protein interacting with Nck, 90 kDa (SPIN90); SPIN90 is also called NCK interacting protein with SH3 domain (NCKIPSD), Dia-interacting protein (DIP), 54 kDa vimentin-interacting protein (VIP54), or WASP-interacting SH3-domain protein (WISH). It is an F-actin binding protein that regulates actin polymerization and endocytosis. It associates with the Arp2/3 complex near actin filaments and determines filament localization at the leading edge of lamellipodia. SPIN90 is expressed in the early stages of neuronal differentiation and plays a role in regulating growth cone dynamics and neurite outgrowth. It also interacts with IRSp53 and regulates cell motility by playing a role in the formation of membrane protrusions. SPIN90 contains an N-terminal SH3 domain, a proline-rich domain, and a C-terminal VCA (verprolin-homology and cofilin-like acidic) domain. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212783 [Multi-domain] Cd Length: 53 Bit Score: 36.91 E-value: 4.78e-03

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|.
gi 1804876928  925 QALCSWTAKKDNHLNFSKHDIITVLEQ-QENWWFGEVHGGR-GWFPKSYVK 973
Cdd:cd11849      3 RALYDFKSAEPNTLSFSEGETFLLLERsNAHWWLVTNHSGEtGYVPANYVK 53

Src Homology 3 domain of fungal BOI-like proteins; This subfamily includes the Saccharomyces cerevisiae proteins BOI1 and BOI2, and similar proteins. They contain an N-terminal SH3 domain, a Sterile alpha motif (SAM), and a Pleckstrin homology (PH) domain at the C-terminus. BOI1 and BOI2 interact with the SH3 domain of Bem1p, a protein involved in bud formation. They promote polarized cell growth and participates in the NoCut signaling pathway, which is involved in the control of cytokinesis. SH3 domains bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs; they play a role in the regulation of enzymes by intramolecular interactions, changing the subcellular localization of signal pathway components and mediate multiprotein complex assemblies.

Pssm-ID: 212819 Cd Length: 55 Bit Score: 36.93 E-value: 4.98e-03

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....*
gi 1804876928  785 YKALYRFEARSHDEMSFNSGDIIQV--DEKTIGEpGWLYGS--FQGNFGWFPCNY 835
Cdd:cd11886      2 LIVIHDFNARSEDELTLKPGDKIELieDDEEFGD-GWYLGRnlRTGETGLFPVVF 55

Third Src Homology 3 domain of SH3 domain containing ring finger 1 (SH3RF1), SH3RF3, and similar domains; SH3RF1 (or POSH) and SH3RF3 (or POSH2) are scaffold proteins that function as E3 ubiquitin-protein ligases. They contain an N-terminal RING finger domain and four SH3 domains. This model represents the third SH3 domain, located in the middle of SH3RF1 and SH3RF3, and similar domains. SH3RF1 plays a role in calcium homeostasis through the control of the ubiquitin domain protein Herp. It may also have a role in regulating death receptor mediated and JNK mediated apoptosis. SH3RF3 interacts with p21-activated kinase 2 (PAK2) and GTP-loaded Rac1. It may play a role in regulating JNK mediated apoptosis in certain conditions. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212717 [Multi-domain] Cd Length: 55 Bit Score: 36.99 E-value: 5.06e-03

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....
gi 1804876928  785 YKALYRFEARSHDEMSFNSGDIIQVDEKTigEPGWLYGS--FQGNFGWFPCNYV 836
Cdd:cd11783      2 YVALYPYKPQKPDELELRKGEMYTVTEKC--QDGWFKGTslRTGQSGVFPGNYV 53

Coiled-coil domain-containing protein 3; This family is found in eukaryotes; it has several conserved tryptophan residues. The function is not known.

Pssm-ID: 464032 [Multi-domain] Cd Length: 221 Bit Score: 40.46 E-value: 5.17e-03

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1804876928  683 LKELResyntQQLALEQLHKIKRDKLKEIERKRSELIQKKKLEDEAIRKAKQGKENL----------WRESLRKEEEEKQ 752
Cdd:pfam13904   85 EAELR-----KRLAKEKYQEWLQRKARQQTKKREESHKQKAAESASKSLAKPERKVSqeeakevlqeWERKKLEQQQRKR 159

                           90
                   ....*....|....*...
gi 1804876928  753 KRLQEEKTQEKVQEEERK 770
Cdd:pfam13904  160 EEEQREQLKKEEEEQERK 177

Src Homology 3 domain of Brain-specific Angiogenesis Inhibitor 1-Associated Protein 2-Like 1, also called Insulin Receptor Tyrosine Kinase Substrate (IRTKS); BAIAP2L1 or IRTKS is widely expressed, serves as a substrate for the insulin receptor, and binds the small GTPase Rac. It plays a role in regulating the actin cytoskeleton and colocalizes with F-actin, cortactin, VASP, and vinculin. BAIAP2L1 expression leads to the formation of short actin bundles, distinct from filopodia-like protrusions induced by the expression of the related protein IRSp53. IRTKS mediates the recruitment of effector proteins Tir and EspFu, which regulate host cell actin reorganization, to bacterial attachment sites. It contains an N-terminal IMD or Inverse-Bin/Amphiphysin/Rvs (I-BAR) domain, an SH3 domain, and a WASP homology 2 (WH2) actin-binding motif at the C-terminus. The SH3 domain of IRTKS has been shown to bind the proline-rich C-terminus of EspFu. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212846 Cd Length: 58 Bit Score: 36.82 E-value: 5.68e-03

                           10        20        30        40
                   ....*....|....*....|....*....|....*....|....*....
gi 1804876928 1088 SGSEQLSLAPGQ-LILILKKNSSGWWQGELQARGkkrQKGWFPASHVKL 1135
Cdd:cd11913     13 NNKTLLSFAQGDvITLLIPEEKDGWLYGEHDTTK---ARGWFPSSYTRP 58

Src Homology 3 domain of Small G protein Signaling Modulator 3; SGSM3 is also called Merlin-associated protein (MAP), RUN and SH3 domain-containing protein (RUSC3), RUN and TBC1 domain-containing protein 3 (RUTBC3), Rab GTPase-activating protein 5 (RabGAP5), or Rab GAP-like protein (RabGAPLP). It is expressed ubiquitously and functions as a regulator of small G protein RAP- and RAB-mediated neuronal signaling. It is involved in modulating NGF-mediated neurite outgrowth and differentiation. It also interacts with the tumor suppressor merlin and may play a role in the merlin-associated suppression of cell growth. SGSM3 contains TBC, SH3, and RUN domains. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212747 Cd Length: 53 Bit Score: 36.71 E-value: 5.72e-03

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|..
gi 1804876928  786 KALYRFEARSHDEMSFNSGDIIQVDEKTiGEPGWLyGSFQGNFGWFPCNYVE 837
Cdd:cd11813      3 KALLDFERHDDDELGFRKNDIITIISQK-DEHCWV-GELNGLRGWFPAKFVE 52

cell envelope integrity inner membrane protein TolA; Provisional

Pssm-ID: 236545 [Multi-domain] Cd Length: 387 Bit Score: 40.95 E-value: 5.72e-03

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1804876928  693 QQLALEQLHKI--KRDKLKEIERKRSELIQKKKLEDEAIRKA----KQGKENLWR-----------------ESLRKEEE 749
Cdd:PRK09510    86 QQQAEELQQKQaaEQERLKQLEKERLAAQEQKKQAEEAAKQAalkqKQAEEAAAKaaaaakakaeaeakraaAAAKKAAA 165

                           90       100       110
                   ....*....|....*....|....*....|....*...
gi 1804876928  750 EKQKRLQEEKTQEKVQEEERKVEEKQCEPASALVNYKA 787
Cdd:PRK09510   166 EAKKKAEAEAAKKAAAEAKKKAEAEAAAKAAAEAKKKA 203

Third Src homology 3 domain of ADAM-binding protein Eve-1; Eve-1, also called SH3 domain-containing protein 19 (SH3D19) or EEN-binding protein (EBP), exists in multiple alternatively spliced isoforms. The longest isoform contains five SH3 domain in the C-terminal region and seven proline-rich motifs in the N-terminal region. It is abundantly expressed in skeletal muscle and heart, and may be involved in regulating the activity of ADAMs (A disintegrin and metalloproteases). Eve-1 interacts with EEN, an endophilin involved in endocytosis and may be the target of the MLL-EEN fusion protein that is implicated in leukemogenesis. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212750 [Multi-domain] Cd Length: 51 Bit Score: 36.62 E-value: 5.73e-03

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|.
gi 1804876928  923 KAQALCSWTAKKDNHLNFSKHDIITVLEQ-QENWWFGEVHGGRGWFPKSYV 972
Cdd:cd11816      1 RCVARFDFEGEQEDELSFSEGDVITLKEYvGEEWAKGELNGKIGIFPLNFV 51

YscO-like protein; This family of proteins is similar to the type III secretion protein YscO. The family includes Chlamydia trachomatis CT670 which is found in a type III secretion gene cluster. CT670 interacts with CT671, a putative YscP homolog and CT670 and CT671 may form a chaperone-effector pair.

Pssm-ID: 435583 [Multi-domain] Cd Length: 160 Bit Score: 39.43 E-value: 5.86e-03

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1804876928  619 KKSLEKEElcQRLKEQLDALEKETASKLSEMDSFNNQLKCGNMDDSVLQCLLsllsclnnlflLLKELRESYNTQQLALE 698
Cdd:pfam16789   27 KRALEKEK--EKLAELEAERDKVRKHKKAKMQQLRDEMDRGTTSDKILQMKR-----------YIKVVKERLKQEEKKVQ 93

                           90       100       110       120       130       140       150
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|..
gi 1804876928  699 QLHKIKRDKLKEIERKRSELIQKKKlEDEAIRKAKQGkenlWRESLRKEEEEKQKRLQEEKTQEKVQEEERK 770
Cdd:pfam16789   94 DQKEQVRTAARNLEIAREELKKKRQ-EVEKLEKHKKE----WVKEMKKEEEDQEEREQDEIGSALHLANQRK 160

Membrane protein TolA involved in colicin uptake [Cell wall/membrane/envelope biogenesis];

Pssm-ID: 442298 [Multi-domain] Cd Length: 485 Bit Score: 41.18 E-value: 6.09e-03

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1804876928  384 QKIQEEEPQKKLPVTFEDKRKANYERGNVElEKRRQALMEQQQREAERKAQKEKEEWERKQRELQEQEwKKQLELEKRLE 463
Cdd:COG3064     25 KRAAAEAEQKAKEEAEEERLAELEAKRQAE-EEAREAKAEAEQRAAELAAEAAKKLAEAEKAAAEAEK-KAAAEKAKAAK 102

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1804876928  464 KQRELERQREEERRKEIERREAAKQELERQRRLEWERiRRQELLNQRNREQEEIVRLNSKKKSLHLELEALNGKHQQISG 543
Cdd:COG3064    103 EAEAAAAAEKAAAAAEKEKAEEAKRKAEEEAKRKAEE-ERKAAEAEAAAKAEAEAARAAAAAAAAAAAAAARAAAGAAAA 181

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1804876928  544 RLQDVRLRKQTQKTEIEVLDKQCDLEIMEIKQLQQELQDYQNKLIYLVPEKQLLNERIKNMQLGNTPDLGIDLLHKKSLE 623
Cdd:COG3064    182 LVAAAAAAVEAADTAAAAAAALAAAAAAAAADAALLALAVAARAAAASREAALAAVEATEEAALGGAEEAADLAAVGVLG 261


                   ...
gi 1804876928  624 KEE 626
Cdd:COG3064    262 AAL 264

Src Homology 3 domain of Amphiphysin and related domains; Amphiphysins function primarily in endocytosis and other membrane remodeling events. They exist in several isoforms and mammals possess two amphiphysin proteins from distinct genes. Amphiphysin I proteins, enriched in the brain and nervous system, contain domains that bind clathrin, Adaptor Protein complex 2 (AP2), dynamin, and synaptojanin. They function in synaptic vesicle endocytosis. Human autoantibodies to amphiphysin I hinder GABAergic signaling and contribute to the pathogenesis of paraneoplastic stiff-person syndrome. Some amphiphysin II isoforms, also called Bridging integrator 1 (Bin1), are localized in many different tissues and may function in intracellular vesicle trafficking. In skeletal muscle, Bin1 plays a role in the organization and maintenance of the T-tubule network. Mutations in Bin1 are associated with autosomal recessive centronuclear myopathy. Amphiphysins contain an N-terminal BAR domain with an additional N-terminal amphipathic helix (an N-BAR), a variable central domain, and a C-terminal SH3 domain. The SH3 domain of amphiphysins bind proline-rich motifs present in binding partners such as dynamin, synaptojanin, and nsP3. It also belongs to a subset of SH3 domains that bind ubiquitin in a site that overlaps with the peptide binding site. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212724 [Multi-domain] Cd Length: 64 Bit Score: 36.92 E-value: 6.17e-03

                           10        20        30        40        50        60
                   ....*....|....*....|....*....|....*....|....*....|....*....|.
gi 1804876928  923 KAQALCSWTAKKDNHLNFSKHDIITVL------EQQENWWFG--EVHGGRGWFPKSYVKII 975
Cdd:cd11790      4 KVRATHDYTAEDTDELTFEKGDVILVIpfddpeEQDEGWLMGvkESTGCRGVFPENFTERI 64

Second Src Homology 3 domain (SH3B) of CD2-associated protein; CD2AP, also called CMS (Cas ligand with Multiple SH3 domains) or METS1 (Mesenchyme-to-Epithelium Transition protein with SH3 domains), is a cytosolic adaptor protein that plays a role in regulating the cytoskeleton. It is critical in cell-to-cell union necessary for kidney function. It also stabilizes the contact between a T cell and antigen-presenting cells. It is primarily expressed in podocytes at the cytoplasmic face of the slit diaphragm and serves as a linker anchoring podocin and nephrin to the actin cytoskeleton. CD2AP contains three SH3 domains, a proline-rich region, and a C-terminal coiled-coil domain. All of these domains enable CD2AP to bind various protein partners and assemble complexes that have been implicated in many different functions. This alignment model represents the second SH3 domain (SH3B) of CD2AP. SH3B binds to c-Cbl in a site (TPSSRPLR is the core binding motif) distinct from the c-Cbl/SH3A binding site. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212987 [Multi-domain] Cd Length: 55 Bit Score: 36.48 E-value: 6.18e-03

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|..
gi 1804876928  923 KAQALCSWTAKKDNHLNFSKHDIITVLEQ-QENWWFGEVHGGRGWFPKSYVK 973
Cdd:cd12054      2 QCKVLFEYVPQNEDELELKVGDIIDINEEvEEGWWSGTLNGKSGLFPSNFVK 53

Src homology 3 domain of Endophilin-B; Endophilins play roles in synaptic vesicle formation, virus budding, mitochondrial morphology maintenance, receptor-mediated endocytosis inhibition, and endosomal sorting. They are classified into two types, A and B. Vertebrates contain two endophilin-B isoforms. Endophilin-B proteins are cytoplasmic proteins expressed mainly in the heart, placenta, and skeletal muscle. Endophilins contain an N-terminal N-BAR domain (BAR domain with an additional N-terminal amphipathic helix), followed by a variable region containing proline clusters, and a C-terminal SH3 domain. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212736 [Multi-domain] Cd Length: 52 Bit Score: 36.50 E-value: 6.20e-03

                           10        20        30        40
                   ....*....|....*....|....*....|....*....|....*....
gi 1804876928 1155 AMYDYVANNEDELNFSKGQLINVLNKD--DPDWWQGEINGVTGLFPSNY 1201
Cdd:cd11802      4 VLYDYDAEDSTELSLLADEVITVYELPgmDEDYMMGERGSQRGKVPVAY 52

Polo kinase kinase; This domain family is found in eukaryotes, and is approximately 140 amino acids in length. The family is found in association with pfam00069. Polo-like kinase 1 (Plx1) is essential during mitosis for the activation of Cdc25C, for spindle assembly, and for cyclin B degradation. This family is Polo kinase kinase (PKK) which phosphorylates Polo kinase and Polo-like kinase to activate them. PKK is a serine/threonine kinase.

Pssm-ID: 463600 [Multi-domain] Cd Length: 139 Bit Score: 38.70 E-value: 6.35e-03

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1804876928  433 AQKEKEEWERKQrELQEQEWKKQLELEK-RLEKQrelerqreeerrkeierreaAKQELER------QRRLEWERIRRQE 505
Cdd:pfam12474    1 HQLQKEQQKDRF-EQERQQLKKRYEKELeQLERQ--------------------QKQQIEKleqrqtQELRRLPKRIRAE 59

                           90       100       110       120       130       140       150
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 1804876928  506 llnQRNREQEEIVRLNSKKKSLHLELEALNGKHQQISGRLQDVRLRKQTQKTEIEVLDKQCDLEIMEIKQLQQE 579
Cdd:pfam12474   60 ---QKKRLKMFRESLKQEKKELKQEVEKLPKFQRKEAKRQRKEELELEQKHEELEFLQAQSEALERELQQLQNE 130

Tektin family; Tektins are cytoskeletal proteins. They have been demonstrated in such cellular sites as centrioles, basal bodies, and along ciliary and flagellar doublet microtubules. Tektins form unique protofilaments, organized as longitudinal polymers of tektin heterodimers with axial periodicity matching tubulin. Tektin polypeptides consist of several alpha-helical regions that are predicted to form coiled coils. Indeed, tektins share considerable structural similarities with intermediate filament proteins. Possible functional roles for tektins are: stabilization of tubulin protofilaments; attachment of A and B-tubules in ciliary/flagellar microtubule doublets and C-tubules in centrioles; binding of axonemal components.

Pssm-ID: 460827 [Multi-domain] Cd Length: 383 Bit Score: 40.99 E-value: 6.35e-03

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1804876928  498 WeRIRRQELLNQ--RNREQEEIVRLNSKKksLHLELEALNGKHQQISG-----RLQDVRLRKQTQKTEIEVLDKQCDLEI 570
Cdd:pfam03148    1 W-RANNQELYREaeAQRNDAERLRQESRR--LRNETDAKTKWDQYDSNrrlgeRIQDITFWKSELEKELEELDEEIELLL 77

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1804876928  571 MEIKQLQQELQDYQNKL---------------IYLV---PEKQLLNER--IKNMQlgntpdlgiDLLhKKSLEK--EELC 628
Cdd:pfam03148   78 EEKRRLEKALEALEEPLhiaqecltlrekrqgIDLVhdeVEKELLKEVelIEGIQ---------ELL-QRTLEQawEQLR 147

                          170       180       190
                   ....*....|....*....|....*....|.
gi 1804876928  629 qRLKEQLDALEKETASKLS--EMDSFNNQLK 657
Cdd:pfam03148  148 -LLRAARHKLEKDLSDKKEalEIDEKCLSLN 177

RecF/RecN/SMC N terminal domain; This domain is found at the N terminus of SMC proteins. The SMC (structural maintenance of chromosomes) superfamily proteins have ATP-binding domains at the N- and C-termini, and two extended coiled-coil domains separated by a hinge in the middle. The eukaryotic SMC proteins form two kind of heterodimers: the SMC1/SMC3 and the SMC2/SMC4 types. These heterodimers constitute an essential part of higher order complexes, which are involved in chromatin and DNA dynamics. This family also includes the RecF and RecN proteins that are involved in DNA metabolism and recombination.

Pssm-ID: 426784 [Multi-domain] Cd Length: 1161 Bit Score: 41.50 E-value: 6.38e-03

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1804876928  368 RGGKQIDSINGTLPSYQKIQEEEPQKKLPVTFEDKRKANYERGNVELEK---RRQALMEQQQR----EAERKAQKEKEEW 440
Cdd:pfam02463  402 EEEKEAQLLLELARQLEDLLKEEKKEELEILEEEEESIELKQGKLTEEKeelEKQELKLLKDElelkKSEDLLKETQLVK 481

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1804876928  441 ERKQRELQEQEWKKQLELEKRLEKQRELERQREEERRKEIERREAAKQELERQ--------------RRLEWERIRRQEL 506
Cdd:pfam02463  482 LQEQLELLLSRQKLEERSQKESKARSGLKVLLALIKDGVGGRIISAHGRLGDLgvavenykvaistaVIVEVSATADEVE 561

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1804876928  507 LNQRNREQEEIVRLNSKKKSLHLELEALNGKHQQISGRLQDVRLRKQTQKTEIEVLD------KQCDLEIMEIKQLQQEL 580
Cdd:pfam02463  562 ERQKLVRALTELPLGARKLRLLIPKLKLPLKSIAVLEIDPILNLAQLDKATLEADEDdkrakvVEGILKDTELTKLKESA 641

                          250       260       270       280       290       300       310       320
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1804876928  581 QDYQNKLIYLVPEKQLLNERIKNMQLGNTPDLGIDLLHKKSLEKEELCQRLKEQLDALEKETASKLSEMDSFNNQLKCGN 660
Cdd:pfam02463  642 KAKESGLRKGVSLEEGLAEKSEVKASLSELTKELLEIQELQEKAESELAKEEILRRQLEIKKKEQREKEELKKLKLEAEE 721

                          330       340       350       360       370       380       390       400
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1804876928  661 MDDSVLQCLL----SLLSCLNNLFLLLKELRESYNTQQLALEQLHKIKRDKLKEIERKRSELIQKKKLEDEAIRKAKQGK 736
Cdd:pfam02463  722 LLADRVQEAQdkinEELKLLKQKIDEEEEEEEKSRLKKEEKEEEKSELSLKEKELAEEREKTEKLKVEEEKEEKLKAQEE 801

                          410       420       430       440
                   ....*....|....*....|....*....|....*....|....*....
gi 1804876928  737 ENLWRESLRKEEEEKQKRLQEEKTQ----------EKVQEEERKVEEKQ 775
Cdd:pfam02463  802 ELRALEEELKEEAELLEEEQLLIEQeekikeeeleELALELKEEQKLEK 850

Src homology 3 domain of RUN and SH3 domain-containing protein 2; RUSC2, also called Iporin or Interacting protein of Rab1, is expressed ubiquitously with highest amounts in the brain and testis. It interacts with the small GTPase Rab1 and the Golgi matrix protein GM130, and may function in linking GTPases to certain intracellular signaling pathways. RUSC proteins are adaptor proteins consisting of RUN, leucine zipper, and SH3 domains. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212890 Cd Length: 52 Bit Score: 36.43 E-value: 7.02e-03

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|.
gi 1804876928 1006 EYIALYSYSSVEPGDLTFIEGEEILVTQK-DGEWWTGSIGDRTGIFPSNYV 1055
Cdd:cd11957      1 EVKALCHHIATEPGQLSFNKGDILQVLSRaDGDWLRCSLGPDSGLVPIAYV 51

hypothetical protein; Provisional

Pssm-ID: 237178 [Multi-domain] Cd Length: 508 Bit Score: 40.85 E-value: 7.02e-03

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1804876928  489 ELERQRRLEWERIR-RQELLNQRNREQEEIVRLNSKKKSLHLELEALNGKHQQISGRLQDVRlrkqTQKTEIEVLDKQCD 567
Cdd:PRK12705    54 LLEAKELLLRERNQqRQEARREREELQREEERLVQKEEQLDARAEKLDNLENQLEEREKALS----ARELELEELEKQLD 129

                           90       100       110       120
                   ....*....|....*....|....*....|....*....|..
gi 1804876928  568 LEIMEIKQLQQE------LQDYQNKLIYlvpEKQLLNERIKN 603
Cdd:PRK12705   130 NELYRVAGLTPEqarkllLKLLDAELEE---EKAQRVKKIEE 168

C-terminal (or second) Src homology 3 domain of VAV2 protein; VAV2 is widely expressed and functions as a guanine nucleotide exchange factor (GEF) for RhoA, RhoB and RhoG and also activates Rac1 and Cdc42. It is implicated in many cellular and physiological functions including blood pressure control, eye development, neurite outgrowth and branching, EGFR endocytosis and degradation, and cell cluster morphology, among others. It has been reported to associate with Nek3. VAV proteins contain several domains that enable their function: N-terminal calponin homology (CH), acidic, RhoGEF (also called Dbl-homologous or DH), Pleckstrin Homology (PH), C1 (zinc finger), SH2, and two SH3 domains. The SH3 domain of VAV is involved in the localization of proteins to specific sites within the cell, by interacting with proline-rich sequences within target proteins. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212910 [Multi-domain] Cd Length: 58 Bit Score: 36.53 E-value: 7.07e-03

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|...
gi 1804876928  924 AQALCSWTAKKDNHLNFSKHDIITVLEQ---QENWWFGEVHGGRGWFPKSYVK 973
Cdd:cd11977      3 AVARYNFAARDMRELSLREGDVVRIYSRiggDQGWWKGETNGRIGWFPSTYVE 55

Src homology 3 domain of Brk (Breast tumor kinase) Protein Tyrosine Kinase (PTK), also called PTK6; Brk is a cytoplasmic (or non-receptor) PTK with limited homology to Src kinases. It has been found to be overexpressed in a majority of breast tumors. It plays roles in normal cell differentiation, proliferation, survival, migration, and cell cycle progression. Brk substrates include RNA-binding proteins (SLM-1/2, Sam68), transcription factors (STAT3/5), and signaling molecules (Akt, paxillin, IRS-4). Src kinases in general contain an N-terminal SH4 domain with a myristoylation site, followed by SH3 and SH2 domains, a tyr kinase domain, and a regulatory C-terminal region containing a conserved tyr; they are activated by autophosphorylation at the tyr kinase domain, but are negatively regulated by phosphorylation at the C-terminal tyr by Csk (C-terminal Src Kinase). However, Brk lacks the N-terminal myristoylation site. The SH3 domain of Src kinases contributes to substrate recruitment by binding adaptor proteins/substrates, and regulation of kinase activity through an intramolecular interaction. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212781 [Multi-domain] Cd Length: 58 Bit Score: 36.38 E-value: 7.30e-03

                           10        20
                   ....*....|....*....|....*...
gi 1804876928  785 YKALYRFEARSHDEMSFNSGDIIQVDEK 812
Cdd:cd11847      2 YKALWDFKARGDEELSFQAGDQFRIAER 29

EF-hand, calcium binding motif, found in homologs of mammalian apoptosis-linked gene 2 protein (ALG-2); The family includes some homologs of mammalian apoptosis-linked gene 2 protein (ALG-2) mainly found in lower eukaryotes, such as a parasitic protist Leishmarua major and a cellular slime mold Dictyostelium discoideum. These homologs contains five EF-hand motifs. Due to the presence of unfavorable residues at the Ca2+-coordinating positions, their non-canonical EF4 and EF5 hands may not bind Ca2+. Two Dictyostelium PEF proteins are the prototypes of this family. They may bind to cytoskeletal proteins and/or signal-transducing proteins localized to detergent-resistant membranes named lipid rafts, and occur as monomers or weak homo- or heterodimers like ALG-2. They can serve as a mediator for Ca2+ signaling-related Dictyostehum programmed cell death (PCD).

Pssm-ID: 320060 [Multi-domain] Cd Length: 163 Bit Score: 39.12 E-value: 7.38e-03

                           10        20        30        40        50        60
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 1804876928  285 RQKFNSLDKSMSGYLSGFQARNALLQSNL--SQTQLATIWTLADIDGDGQLRAEEFiLAMH--LTDM 347
Cdd:cd16185      3 RQWFRAVDRDRSGSIDVNELQKALAGGGLlfSLATAEKLIRMFDRDGNGTIDFEEF-AALHqfLSNM 68

Src Homology 3 domain of Src Kinase-Associated Phosphoprotein 1; SKAP1, also called SKAP55 (Src kinase-associated protein of 55kDa), is an immune cell-specific adaptor protein that plays an important role in T-cell adhesion, migration, and integrin clustering. It is expressed exclusively in T-lymphocytes, mast cells, and macrophages. Binding partners include ADAP (adhesion and degranulation-promoting adaptor protein), Fyn, Riam, RapL, and RasGRP. It contains a pleckstrin homology (PH) domain, a C-terminal SH3 domain, and several tyrosine phosphorylation sites. The SH3 domain of SKAP1 is necessary for its ability to regulate T-cell conjugation with antigen-presenting cells and the formation of LFA-1 clusters. SKAP1 binds primarily to a proline-rich region of ADAP through its SH3 domain; its degradation is regulated by ADAP. A secondary interaction occurs via the ADAP SH3 domain and the RKxxYxxY motif in SKAP1. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212977 Cd Length: 53 Bit Score: 36.37 E-value: 7.49e-03

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|.
gi 1804876928  925 QALCSWTAKKDNHLNFSKHDIITVLEQQEN---WWFGEVHGGRGWFPKSYV 972
Cdd:cd12044      3 QGLWDCFGDNPDELSFQRGDLIYILSKEYNmygWWVGELNGIVGIVPKDYL 53

Src Homology 3 domain of Class A Dedicator of Cytokinesis proteins 1 and 5; Dock1, also called Dock180, and Dock5 are class A DOCKs and are atypical guanine nucleotide exchange factors (GEFs) that lack the conventional Dbl homology (DH) domain. Dock1 interacts with the scaffold protein Elmo and the resulting complex functions upstream of Rac in many biological events including phagocytosis of apoptotic cells, cell migration and invasion. Dock5 functions upstream of Rac1 to regulate osteoclast function. All DOCKs contain two homology domains: the DHR-1 (Dock homology region-1), also called CZH1 (CED-5, Dock180, and MBC-zizimin homology 1), and DHR-2 (also called CZH2 or Docker). The DHR-1 domain binds phosphatidylinositol-3,4,5-triphosphate while DHR-2 contains the catalytic activity for Rac and/or Cdc42. Class A DOCKs also contain an SH3 domain at the N-terminal region and a PxxP motif at the C-terminus; they are specific GEFs for Rac. The SH3 domain of Dock1 binds to DHR-2 in an autoinhibitory manner; binding of Elmo to the SH3 domain of Dock1 exposes the DHR-2 domain and promotes GEF activity. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212984 [Multi-domain] Cd Length: 56 Bit Score: 36.34 E-value: 7.60e-03

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|.
gi 1804876928 1085 YVASGSEQLSLAPGQLILILKkNSSGWWQGelQARGKKRQKGWFPASHVKL 1135
Cdd:cd12051      8 YDARGPDELSLQIGDTVHILE-TYEGWYRG--YTLRKKSKKGIFPASYIHL 55

Uncharacterized conserved protein, contains a C-terminal ATPase domain [Function unknown];

Pssm-ID: 443941 [Multi-domain] Cd Length: 1089 Bit Score: 41.05 E-value: 7.61e-03

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1804876928  413 ELEKRRQALMEQQQREAERK--AQKEKEEWERKQRELQEQEWKKQLELEKRLEKQRELERqreeerrkeierreAAKQEL 490
Cdd:COG4913    292 LLEAELEELRAELARLEAELerLEARLDALREELDELEAQIRGNGGDRLEQLEREIERLE--------------RELEER 357

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1804876928  491 ERQR-----------------RLEWERIRRQ-------------ELLNQRNREQEEIVRLNSKKKSLHLELEALNGKHQQ 540
Cdd:COG4913    358 ERRRarleallaalglplpasAEEFAALRAEaaallealeeeleALEEALAEAEAALRDLRRELRELEAEIASLERRKSN 437

                          170       180
                   ....*....|....*....|...
gi 1804876928  541 ISGRLQDVR--LRKQTQKTEIEV 561
Cdd:COG4913    438 IPARLLALRdaLAEALGLDEAEL 460

Src homology 3 domain of Abl Interactor 2; Abi2 is highly expressed in the brain and eye. It regulates actin cytoskeletal reorganization at adherens junctions and dendritic spines, which is important in cell morphogenesis, migration, and cognitive function. Mice deficient with Abi2 show defects in orientation and migration of lens fibers, neuronal migration, dendritic spine morphology, as well as deficits in learning and memory. Abi proteins are adaptor proteins serving as binding partners and substrates of Abl tyrosine kinases. They are involved in regulating actin cytoskeletal reorganization and play important roles in membrane-ruffling, endocytosis, cell motility, and cell migration. Abi proteins contain a homeobox homology domain, a proline-rich region, and a SH3 domain. The SH3 domain of Abi binds to a PxxP motif in Abl. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212905 [Multi-domain] Cd Length: 61 Bit Score: 36.53 E-value: 7.64e-03

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....*.
gi 1804876928 1085 YVASGSEQLSLAPGQLILILKKNSSGWWQGELQArgkkrQKGWFPASHVK-LLGPS 1139
Cdd:cd11972     11 YTKDKEDELSFQEGAIIYVIKKNDDGWYEGVMNG-----VTGLFPGNYVEsIMHYS 61

Src homology 3 domain of Abl Interactor 2; Abi2 is highly expressed in the brain and eye. It regulates actin cytoskeletal reorganization at adherens junctions and dendritic spines, which is important in cell morphogenesis, migration, and cognitive function. Mice deficient with Abi2 show defects in orientation and migration of lens fibers, neuronal migration, dendritic spine morphology, as well as deficits in learning and memory. Abi proteins are adaptor proteins serving as binding partners and substrates of Abl tyrosine kinases. They are involved in regulating actin cytoskeletal reorganization and play important roles in membrane-ruffling, endocytosis, cell motility, and cell migration. Abi proteins contain a homeobox homology domain, a proline-rich region, and a SH3 domain. The SH3 domain of Abi binds to a PxxP motif in Abl. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212905 [Multi-domain] Cd Length: 61 Bit Score: 36.53 E-value: 7.72e-03

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....*.
gi 1804876928  923 KAQALCSWTAKKDNHLNFSKHDIITVLEQQENWWF-GEVHGGRGWFPKSYVKIIPG 977
Cdd:cd11972      4 KVVAIYDYTKDKEDELSFQEGAIIYVIKKNDDGWYeGVMNGVTGLFPGNYVESIMH 59

First Src Homology 3 domain of Vinexin, also called Sorbin and SH3 domain containing 3 (Sorbs3); Vinexin is also called Sorbs3, SH3P3, and SH3-containing adapter molecule 1 (SCAM-1). It is an adaptor protein containing one sorbin homology (SoHo) and three SH3 domains. Vinexin was first identified as a vinculin binding protein; it is co-localized with vinculin at cell-ECM and cell-cell adhesion sites. There are several splice variants of vinexin: alpha, which contains the SoHo and three SH3 domains and displays tissue-specific expression; and beta, which contains only the three SH3 domains and is widely expressed. Vinexin alpha stimulates the accumulation of F-actin at focal contact sites. Vinexin also promotes keratinocyte migration and wound healing. The SH3 domains of vinexin have been reported to bind a number of ligands including vinculin, WAVE2, DLG5, Abl, and Cbl. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212854 Cd Length: 55 Bit Score: 36.44 E-value: 7.99e-03

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....
gi 1804876928  923 KAQALCSWTAKKDNHLNFSKHDIITVLEQ-QENWWFGEVHGGRGWFPKSYVKII 975
Cdd:cd11921      2 AARLKFDFQAQSPKELTLQKGDIVYIHKEvDKNWLEGEHHGRVGIFPANYVEVL 55

Src Homology 3 domain of Epidermal growth factor receptor kinase substrate 8 and similar proteins; This group is composed of Eps8 and Eps8-like proteins including Eps8-like 1-3, among others. These proteins contain N-terminal Phosphotyrosine-binding (PTB), central SH3, and C-terminal effector domains. Eps8 binds either Abi1 (also called E3b1) or Rab5 GTPase activating protein RN-tre through its SH3 domain. With Abi1 and Sos1, it becomes part of a trimeric complex that is required to activate Rac. Together with RN-tre, it inhibits the internalization of EGFR. The SH3 domains of Eps8 and similar proteins recognize peptides containing a PxxDY motif, instead of the classical PxxP motif. SH3 domains are protein interaction domains that usually bind to proline-rich ligands with moderate affinity and selectivity. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212698 [Multi-domain] Cd Length: 54 Bit Score: 36.09 E-value: 8.02e-03

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....
gi 1804876928 1153 VIAMYDYVANNEDELNFSKGQLINVLNkDDPDWWQGE-INGVTGLFPSNYVKMT 1205
Cdd:cd11764      2 VRVLYDFTARNSKELSVLKGEYLEVLD-DSRQWWKVRnSRGQVGYVPHNILEPY 54

V-type ATP synthase subunit H; Validated

Pssm-ID: 169428 [Multi-domain] Cd Length: 103 Bit Score: 37.85 E-value: 8.07e-03

                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 1804876928  706 DKLKEI---ERKRSELIQKKKLEDEAI-RKAKQGKENLWRESLRKEEEEKQKrLQEEKTQEKVQEEERKVEEKQCE 777
Cdd:PRK08404     3 DVIKEIvkaEKEAEERIEKAKEEAKKIiRKAKEEAKKIEEEIIKKAEEEAQK-LIEKKKKEGEEEAKKILEEGEKE 77

Ezrin/radixin/moesin, alpha-helical domain; The ERM family consists of three closely-related proteins, ezrin, radixin and moesin. Ezrin was first identified as a constituent of microvilli, radixin as a barbed, end-capping actin-modulating protein from isolated junctional fractions, and moesin as a heparin binding protein. A tumour suppressor molecule responsible for neurofibromatosis type 2 (NF2) is highly similar to ERM proteins and has been designated merlin (moesin-ezrin-radixin-like protein). ERM molecules contain 3 domains, an N-terminal globular domain, an extended alpha-helical domain and a charged C-terminal domain (pfam00769). Ezrin, radixin and merlin also contain a polyproline linker region between the helical and C-terminal domains. The N-terminal domain is highly conserved and is also found in merlin, band 4.1 proteins and members of the band 4.1 superfamily, designated the FERM domain. ERM proteins crosslink actin filaments with plasma membranes. They co-localize with CD44 at actin filament plasma membrane interaction sites, associating with CD44 via their N-terminal domains and with actin filaments via their C-terminal domains. This is the alpha-helical domain, which is involved in intramolecular masking of protein-protein interaction sites, regulating the activity of this proteins.

Pssm-ID: 466641 [Multi-domain] Cd Length: 120 Bit Score: 37.98 E-value: 8.10e-03

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1804876928  684 KELRESYNTQQLALEQLHKIKRDKlKEIERKRSELIQ-KKKLEDEAIRKAKQgKENLWREslRKEEEEKQKRLQEEKT-- 760
Cdd:pfam20492   27 EELEESEETAEELEEERRQAEEEA-ERLEQKRQEAEEeKERLEESAEMEAEE-KEQLEAE--LAEAQEEIARLEEEVErk 102

                           90
                   ....*....|....*..
gi 1804876928  761 -------QEKVQEEERK 770
Cdd:pfam20492  103 eeearrlQEELEEAREE 119

Second Src homology 3 domain (or SH3B) of Intersectin-1; Intersectin-1 (ITSN1) is an adaptor protein that functions in exo- and endocytosis, actin cytoskeletal reorganization, and signal transduction. It plays a role in clathrin-coated pit (CCP) formation. It binds to many proteins through its multidomain structure and facilitate the assembly of multimeric complexes. ITSN1 localizes in membranous organelles, CCPs, the Golgi complex, and may be involved in the cell membrane trafficking system. It exists in alternatively spliced short and long isoforms. The short isoform contains two Eps15 homology domains (EH1 and EH2), a coiled-coil region and five SH3 domains (SH3A-E), while the long isoform, in addition, contains RhoGEF (also called Dbl-homologous or DH), Pleckstrin homology (PH) and C2 domains. The second SH3 domain (or SH3B) of ITSN1 has been shown to bind WNK and CdGAP. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212922 [Multi-domain] Cd Length: 52 Bit Score: 36.23 E-value: 8.72e-03

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....*..
gi 1804876928 1079 AQVTSAYVASGSEQLSLAPGQLILILKKNSSgWWQGELQArgkkrQKGWFPASHVKL 1135
Cdd:cd11989      2 AQALYPWRAKKDNHLNFNKNDVITVLEQQDM-WWFGEVQG-----QKGWFPKSYVKL 52

recombination and DNA strand exchange inhibitor protein; Reviewed

Pssm-ID: 234750 [Multi-domain] Cd Length: 782 Bit Score: 40.97 E-value: 8.74e-03

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1804876928  683 LKELRESYNTQQLALEQLHKIKRDKLKEIERKRSELIQKKKLEDEAIRKAKQGKENLWRE---SLRKEEEEKQKRLQEEK 759
Cdd:PRK00409   518 LNELIASLEELERELEQKAEEAEALLKEAEKLKEELEEKKEKLQEEEDKLLEEAEKEAQQaikEAKKEADEIIKELRQLQ 597

                           90
                   ....*....|....*.
gi 1804876928  760 TQEKVQEEERKVEEKQ 775
Cdd:PRK00409   598 KGGYASVKAHELIEAR 613

C-terminal Src Homology 3 domain of NADPH oxidase activator 1; Noxa1 is a homolog of p67phox and is a cytosolic subunit of the nonphagocytic NADPH oxidase complex Nox1, which catalyzes the transfer of electrons from NADPH to molecular oxygen to form superoxide. Noxa1 is co-expressed with Nox1 in colon, stomach, uterus, prostate, and vascular smooth muscle cells, consistent with its regulatory role. It does not interact with p40phox, unlike p67phox, making Nox1 activity independent of p40phox, unlike Nox2. Noxa1 contains TPR, PB1, and C-terminal SH3 domains, but lacks the central SH3 domain that is present in p67phox. The TPR domain binds activated GTP-bound Rac. The C-terminal SH3 domain binds the polyproline motif found at the C-terminus of Noxo1, a homolog of p47phox. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212980 Cd Length: 53 Bit Score: 35.95 E-value: 9.01e-03

                           10        20        30        40
                   ....*....|....*....|....*....|....*....|....*...
gi 1804876928  926 ALCSWTAKKDNHLNFSKHDIITVL-EQQENWWFGEVHGGRGWFPKSYV 972
Cdd:cd12047      4 AQHDYSAQGPEDLEFSQGDTIDILsEVNQEWLEGHCDGRIGIFPKCFA 51

Src homology 3 domain of CAS (Crk-Associated Substrate) scaffolding proteins; CAS proteins function as molecular scaffolds to regulate protein complexes that are involved in many cellular processes including migration, chemotaxis, apoptosis, differentiation, and progenitor cell function. They mediate the signaling of integrins at focal adhesions where they localize, and thus, regulate cell invasion and survival. Over-expression of these proteins is implicated in poor prognosis, increased metastasis, and resistance to chemotherapeutics in many cancers such as breast, lung, melanoma, and glioblastoma. CAS proteins have also been linked to the pathogenesis of inflammatory disorders, Alzheimer's, Parkinson's, and developmental defects. They share a common domain structure that includes an N-terminal SH3 domain, an unstructured substrate domain that contains many YxxP motifs, a serine-rich four-helix bundle, and a FAT-like C-terminal domain. Vertebrates contain four CAS proteins: BCAR1 (or p130Cas), NEDD9 (or HEF1), EFS (or SIN), and CASS4 (or HEPL). The SH3 domain of CAS proteins binds to diverse partners including FAK, FRNK, Pyk2, PTP-PEST, DOCK180, among others. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212778 Cd Length: 56 Bit Score: 36.17 E-value: 9.13e-03

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|..
gi 1804876928 1009 ALYSYSSVEPGDLTFIEGEEILVTQKDGE----WWTGSIGDRTGIFPSNYVK 1056
Cdd:cd11844      4 ALYDNVAESPDELAFRRGDILTVLEQNTAglegWWLCSLRGRQGIAPGNRLK 55

Spc7 kinetochore protein; This domain is found in cell division proteins which are required for kinetochore-spindle association.

Pssm-ID: 197874 [Multi-domain] Cd Length: 312 Bit Score: 40.00 E-value: 9.49e-03

                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1804876928   497 EWeriRRQELLNQRNREQEEIVRLNSKKKSLHLELEALNGKHQQISGRLQDVR-----LRKQT-------------QKTE 558
Cdd:smart00787  136 EW---RMKLLEGLKEGLDENLEGLKEDYKLLMKELELLNSIKPKLRDRKDALEeelrqLKQLEdeledcdpteldrAKEK 212

                            90       100       110       120       130       140       150       160
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1804876928   559 IEVLDKQCDLEIMEIKQLQQELQDYQNKLIYLVPEKQLLNERIKNMQlgntpdlgidllhkKSLEKEELC-----QRLKE 633
Cdd:smart00787  213 LKKLLQEIMIKVKKLEELEEELQELESKIEDLTNKKSELNTEIAEAE--------------KKLEQCRGFtfkeiEKLKE 278


                    ....*....
gi 1804876928   634 QLDALEKET 642
Cdd:smart00787  279 QLKLLQSLT 287

calmodulin; Provisional

Pssm-ID: 185504 [Multi-domain] Cd Length: 149 Bit Score: 38.59 E-value: 9.61e-03

                           10        20        30        40        50        60
                   ....*....|....*....|....*....|....*....|....*....|....*....|..
gi 1804876928  283 KYRQKFNSLDKSMSGYLSGFQARNAL--LQSNLSQTQLATIWTLADIDGDGQLRAEEFILAM 342
Cdd:PTZ00184    85 EIKEAFKVFDRDGNGFISAAELRHVMtnLGEKLTDEEVDEMIREADVDGDGQINYEEFVKMM 146