Src homology 3 domain of Ubiquitin-associated and SH3 domain-containing protein B; UBASH3B, also called Suppressor of T cell receptor Signaling (STS)-1 or T cell Ubiquitin LigAnd (TULA)-2 is an active phosphatase that is expressed ubiquitously. The phosphatase activity of UBASH3B is essential for its roles in the suppression of TCR signaling and the regulation of EGFR. It also interacts with Syk and functions as a negative regulator of platelet glycoprotein VI signaling. TULA proteins 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. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|..
gi 1720432874 123 HETLQVIYPYSPQNDDELELVPGDFIFMSPMEQTSTSEGWIYGTSLTTGCSGLLPENYITKA 184
Cdd:cd11936     1 HETLQVIYPYTPQNDDELELVPGDYIFMSPMEQTSTSEGWIYGTSLTTGCSGLLPENYITKA 62

Src homology 3 domain of Ubiquitin-associated and SH3 domain-containing protein B; UBASH3B, also called Suppressor of T cell receptor Signaling (STS)-1 or T cell Ubiquitin LigAnd (TULA)-2 is an active phosphatase that is expressed ubiquitously. The phosphatase activity of UBASH3B is essential for its roles in the suppression of TCR signaling and the regulation of EGFR. It also interacts with Syk and functions as a negative regulator of platelet glycoprotein VI signaling. TULA proteins 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. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|..
gi 1720432874 123 HETLQVIYPYSPQNDDELELVPGDFIFMSPMEQTSTSEGWIYGTSLTTGCSGLLPENYITKA 184
Cdd:cd11936     1 HETLQVIYPYTPQNDDELELVPGDYIFMSPMEQTSTSEGWIYGTSLTTGCSGLLPENYITKA 62

Histidine phosphatase superfamily (branch 1); The histidine phosphatase superfamily is so named because catalysis centres on a conserved His residue that is transiently phosphorylated during the catalytic cycle. Other conserved residues contribute to a 'phosphate pocket' and interact with the phospho group of substrate before, during and after its transfer to the His residue. Structure and sequence analyses show that different families contribute different additional residues to the 'phosphate pocket' and, more surprisingly, differ in the position, in sequence and in three dimensions, of a catalytically essential acidic residue. The superfamily may be divided into two main branches. The larger branch 1 contains a wide variety of catalytic functions, the best known being fructose 2,6-bisphosphatase (found in a bifunctional protein with 2-phosphofructokinase) and cofactor-dependent phosphoglycerate mutase. The latter is an unusual example of a mutase activity in the superfamily: the vast majority of members appear to be phosphatases. The bacterial regulatory protein phosphatase SixA is also in branch 1 and has a minimal, and possible ancestral-like structure, lacking the large domain insertions that contribute to binding of small molecules in branch 1 members.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1720432874 305 DAPITVFGCMQARLVGEALLESNtvIDHVYCSPSLRCVQTAHNILKGLQqdnhLKIRVEPGLFEW--------TKWVAGS 376
Cdd:pfam00300  22 DSPLTELGREQAEALAERLAGEP--FDAIYSSPLKRARQTAEIIAEALG----LPVEIDPRLREIdfgdweglTFEEIAE 95

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1720432874 377 TLPAWippselAAANLSVDTTYRPHIPvsklaisESYDTYINRSFQVTKEIISecKSKGNNILIVAHASSLEACTCQLQG 456
Cdd:pfam00300  96 RYPEE------YDAWLADPADYRPPGG-------ESLADVRARVRAALEELAA--RHPGKTVLVVSHGGVIRALLAHLLG 160

                         170
                  ....*....|.
gi 1720432874 457 LSPQNSKDFVQ 467
Cdd:pfam00300 161 LPLEALRRFPL 171

Phosphoglycerate mutase family; Phosphoglycerate mutase (PGAM) and bisphosphoglycerate mutase (BPGM) are structurally related enzymes that catalyse reactions involving the transfer of phospho groups between the three carbon atoms of phosphoglycerate... Both enzymes can catalyse three different reactions with different specificities, the isomerization of 2-phosphoglycerate (2-PGA) to 3-phosphoglycerate (3-PGA) with 2,3-diphosphoglycerate (2,3-DPG) as the primer of the reaction, the synthesis of 2,3-DPG from 1,3-DPG with 3-PGA as a primer and the degradation of 2,3-DPG to 3-PGA (phosphatase activity). In mammals, PGAM is a dimeric protein with two isoforms, the M (muscle) and B (brain) forms. In yeast, PGAM is a tetrameric protein.

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1720432874  305 DAPITVFGCMQARLVGEALLE-SNTVIDHVYCSPSLRCVQTAHNILKGLQQDnHLKIRvEPGLFEwtkwvaGSTLPAWI- 382
Cdd:smart00855  23 DVPLTELGRAQAEALGRLLASlLLPRFDVVYSSPLKRARQTAEALAIALGLP-GLRER-DFGAWE------GLTWDEIAa 94

                           90       100       110       120       130       140
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 1720432874  383 -PPSELAAANLSVDTTYRPHIPVsklaiSESYDTYINRSFQVTKEIISECKSKGNNILIVAHASSL 447
Cdd:smart00855  95 kYPEEYLAAWRDPYDPAPPAPPG-----GESLADLVERVEPALDELIATADASGQNVLIVSHGGVI 155

alpha-ribazole phosphatase; Members of this protein family include the known CobC protein of Salmonella and Eschichia coli species, and homologous proteins found in cobalamin biosynthesis regions in other bacteria. This protein is alpha-ribazole phosphatase (EC 3.1.3.73) and, like many phosphatases, can be closely related in sequence to other phosphatases with different functions. Close homologs excluded from this model include proteins with duplications, so this model is built in -g mode to suppress hits to those proteins. [Biosynthesis of cofactors, prosthetic groups, and carriers, Heme, porphyrin, and cobalamin]

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1720432874 305 DAPITVFGCMQARLVGEALleSNTVIDHVYCSPSLRCVQTAHNILKGLqqdnHLKIRVEPGLFE--WTKWvAGstlpawI 382
Cdd:TIGR03162  21 DVPLAESGEEQAAALREKL--ADVPFDAVYSSPLSRCRELAEILAERR----GLPIIKDDRLREmdFGDW-EG------R 87

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1720432874 383 PPSELAAANLSVDTTYR--PHIPVSKlaiSESYDTYINRSFQVTKEIISEckSKGNNILIVAHASSLEACTCQLQGLSPQ 460
Cdd:TIGR03162  88 SWDEIPEAYPELDAWAAdwQHARPPG---GESFADFYQRVSEFLEELLKA--HEGDNVLIVTHGGVIRALLAHLLGLPLE 162

phosphoglycerate mutase like-protein; Provisional

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1720432874 305 DAPITVFGCMQARLVGEALLESNTVIDHVYCSPSLRCVQTAHNILKGLqqdNHLKIRVE-------------PGL--FEW 369
Cdd:PTZ00123   12 DVPLSEKGVQEAREAGKLLKEKGFRFDVVYTSVLKRAIKTAWIVLEEL---GQLHVPVIkswrlnerhygalQGLnkSET 88

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1720432874 370 TKWVAGSTLPAW-----IPPSELAAANL---SVDTTYRpHIPVSKLAISESYDTYINRSFQVTKEIISECKSKGNNILIV 441
Cdd:PTZ00123   89 AEKHGEEQVKIWrrsydIPPPPLEKSDErypGNDPVYK-DIPKDALPNTECLKDTVERVLPYWEDHIAPDILAGKKVLVA 167

                         170
                  ....*....|....*....
gi 1720432874 442 AHASSLEACTCQLQGLSPQ 460
Cdd:PTZ00123  168 AHGNSLRALVKYLDKMSEE 186

Src homology 3 domain of Ubiquitin-associated and SH3 domain-containing protein B; UBASH3B, also called Suppressor of T cell receptor Signaling (STS)-1 or T cell Ubiquitin LigAnd (TULA)-2 is an active phosphatase that is expressed ubiquitously. The phosphatase activity of UBASH3B is essential for its roles in the suppression of TCR signaling and the regulation of EGFR. It also interacts with Syk and functions as a negative regulator of platelet glycoprotein VI signaling. TULA proteins 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. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|..
gi 1720432874 123 HETLQVIYPYSPQNDDELELVPGDFIFMSPMEQTSTSEGWIYGTSLTTGCSGLLPENYITKA 184
Cdd:cd11936     1 HETLQVIYPYTPQNDDELELVPGDYIFMSPMEQTSTSEGWIYGTSLTTGCSGLLPENYITKA 62

Src homology 3 domain of Ubiquitin-associated and SH3 domain-containing protein A; UBASH3A is also called Cbl-Interacting Protein 4 (CLIP4), T cell Ubiquitin LigAnd (TULA), or T cell receptor Signaling (STS)-2. It is only found in lymphoid cells and exhibits weak phosphatase activity. UBASH3A facilitates T cell-induced apoptosis through interaction with the apoptosis-inducing factor AIF. It is involved in regulating the level of phosphorylation of the zeta-associated protein (ZAP)-70 tyrosine kinase. TULA proteins 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. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....*..
gi 1720432874 124 ETLQVIYPYSPQNDDELELVPGDFIFMSPMEQTSTSEGWIYGTSLTTGCSGLLPENY 180
Cdd:cd11937     1 QTLRALFQYKPQNIDELMLSPGDYIFVDPTQQSEASEGWVIGISHRTGCRGFLPENY 57

Histidine phosphatase superfamily (branch 1); The histidine phosphatase superfamily is so named because catalysis centres on a conserved His residue that is transiently phosphorylated during the catalytic cycle. Other conserved residues contribute to a 'phosphate pocket' and interact with the phospho group of substrate before, during and after its transfer to the His residue. Structure and sequence analyses show that different families contribute different additional residues to the 'phosphate pocket' and, more surprisingly, differ in the position, in sequence and in three dimensions, of a catalytically essential acidic residue. The superfamily may be divided into two main branches. The larger branch 1 contains a wide variety of catalytic functions, the best known being fructose 2,6-bisphosphatase (found in a bifunctional protein with 2-phosphofructokinase) and cofactor-dependent phosphoglycerate mutase. The latter is an unusual example of a mutase activity in the superfamily: the vast majority of members appear to be phosphatases. The bacterial regulatory protein phosphatase SixA is also in branch 1 and has a minimal, and possible ancestral-like structure, lacking the large domain insertions that contribute to binding of small molecules in branch 1 members.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1720432874 305 DAPITVFGCMQARLVGEALLESNtvIDHVYCSPSLRCVQTAHNILKGLQqdnhLKIRVEPGLFEW--------TKWVAGS 376
Cdd:pfam00300  22 DSPLTELGREQAEALAERLAGEP--FDAIYSSPLKRARQTAEIIAEALG----LPVEIDPRLREIdfgdweglTFEEIAE 95

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1720432874 377 TLPAWippselAAANLSVDTTYRPHIPvsklaisESYDTYINRSFQVTKEIISecKSKGNNILIVAHASSLEACTCQLQG 456
Cdd:pfam00300  96 RYPEE------YDAWLADPADYRPPGG-------ESLADVRARVRAALEELAA--RHPGKTVLVVSHGGVIRALLAHLLG 160

                         170
                  ....*....|.
gi 1720432874 457 LSPQNSKDFVQ 467
Cdd:pfam00300 161 LPLEALRRFPL 171

Broad specificity phosphatase PhoE [Carbohydrate transport and metabolism];

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1720432874 305 DAPITVFGCMQARLVGEALleSNTVIDHVYCSPSLRCVQTAHNILKGLqqdnHLKIRVEPGLFEWtkwvagsTLPAW--I 382
Cdd:COG0406    25 DVPLTELGRAQARALAERL--ADIPFDAVYSSPLQRARQTAEALAEAL----GLPVEVDPRLREI-------DFGDWegL 91

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1720432874 383 PPSELAAANLSVDTTYRPHIPVSKLAISESYDTYINRSFQVTKEIISecKSKGNNILIVAHASSLEACTCQLQGLSPQNS 462
Cdd:COG0406    92 TFAELEARYPEALAAWLADPAEFRPPGGESLADVQARVRAALEELLA--RHPGGTVLVVTHGGVIRALLAHLLGLPLEAF 169

                  ...
gi 1720432874 463 KDF 465
Cdd:COG0406   170 WRL 172

Phosphoglycerate mutase family; Phosphoglycerate mutase (PGAM) and bisphosphoglycerate mutase (BPGM) are structurally related enzymes that catalyse reactions involving the transfer of phospho groups between the three carbon atoms of phosphoglycerate... Both enzymes can catalyse three different reactions with different specificities, the isomerization of 2-phosphoglycerate (2-PGA) to 3-phosphoglycerate (3-PGA) with 2,3-diphosphoglycerate (2,3-DPG) as the primer of the reaction, the synthesis of 2,3-DPG from 1,3-DPG with 3-PGA as a primer and the degradation of 2,3-DPG to 3-PGA (phosphatase activity). In mammals, PGAM is a dimeric protein with two isoforms, the M (muscle) and B (brain) forms. In yeast, PGAM is a tetrameric protein.

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1720432874  305 DAPITVFGCMQARLVGEALLE-SNTVIDHVYCSPSLRCVQTAHNILKGLQQDnHLKIRvEPGLFEwtkwvaGSTLPAWI- 382
Cdd:smart00855  23 DVPLTELGRAQAEALGRLLASlLLPRFDVVYSSPLKRARQTAEALAIALGLP-GLRER-DFGAWE------GLTWDEIAa 94

                           90       100       110       120       130       140
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 1720432874  383 -PPSELAAANLSVDTTYRPHIPVsklaiSESYDTYINRSFQVTKEIISECKSKGNNILIVAHASSL 447
Cdd:smart00855  95 kYPEEYLAAWRDPYDPAPPAPPG-----GESLADLVERVEPALDELIATADASGQNVLIVSHGGVI 155

alpha-ribazole phosphatase; Members of this protein family include the known CobC protein of Salmonella and Eschichia coli species, and homologous proteins found in cobalamin biosynthesis regions in other bacteria. This protein is alpha-ribazole phosphatase (EC 3.1.3.73) and, like many phosphatases, can be closely related in sequence to other phosphatases with different functions. Close homologs excluded from this model include proteins with duplications, so this model is built in -g mode to suppress hits to those proteins. [Biosynthesis of cofactors, prosthetic groups, and carriers, Heme, porphyrin, and cobalamin]

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1720432874 305 DAPITVFGCMQARLVGEALleSNTVIDHVYCSPSLRCVQTAHNILKGLqqdnHLKIRVEPGLFE--WTKWvAGstlpawI 382
Cdd:TIGR03162  21 DVPLAESGEEQAAALREKL--ADVPFDAVYSSPLSRCRELAEILAERR----GLPIIKDDRLREmdFGDW-EG------R 87

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1720432874 383 PPSELAAANLSVDTTYR--PHIPVSKlaiSESYDTYINRSFQVTKEIISEckSKGNNILIVAHASSLEACTCQLQGLSPQ 460
Cdd:TIGR03162  88 SWDEIPEAYPELDAWAAdwQHARPPG---GESFADFYQRVSEFLEELLKA--HEGDNVLIVTHGGVIRALLAHLLGLPLE 162

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.

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....*..
gi 1720432874 125 TLQVIYPYSPQNDDELELVPGDFIfmSPMEQtsTSEGWIYGTSLTTGCSGLLPENYI 181
Cdd:cd11916     3 SYQALYSYAPQNDDELELRDGDIV--DVMEK--CDDGWFVGTSRRTKQFGTFPGNYV 55

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.

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|
gi 1720432874 125 TLQVIYPYSPQNDDELELVPGDFI----FMSPMEQtstSEGWIYGTSLTTGCSGLLPENY 180
Cdd:cd11790     4 KVRATHDYTAEDTDELTFEKGDVIlvipFDDPEEQ---DEGWLMGVKESTGCRGVFPENF 60

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.

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....*
gi 1720432874 129 IYPYSPQNDDELELVPGDFIFmspmEQTSTSEGWIYGTSLTTGCSGLLPENYITK 183
Cdd:cd11789     5 MYDYAAADDDEVSFQEGDVII----NVEIIDDGWMEGTVQRTGQSGMLPANYVEL 55

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.

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|
gi 1720432874 124 ETLQVIYPYSPQNDDELELVPGDFIfmSPMEQtsTSEGWIYGTSLTTGCSGLLPENYITK 183
Cdd:cd11917     5 EPFQALYNYMPRNEDELELREGDVI--DVMEK--CDDGWFVGTSRRTKFFGTFPGNYVKR 60

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.

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....*...
gi 1720432874 124 ETLQVIYPYSPQNDDELELVPGDFIfmspMEQTSTSEGWIYGTSLTTGCSGLLPENYI 181
Cdd:cd11933     2 KSFRAMYDYRAADDDEVSFKDGDTI----VNVQTIDEGWMYGTVQRTGKTGMLPANYV 55

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.

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....*
gi 1720432874 127 QVIYPYSPQNDDELELVPGDFIFMSPMEQtstsEGWIYGTSLTTGCSGLLPENYI 181
Cdd:cd11785     3 RVIVPYPPQSEAELELKEGDIVFVHKKRE----DGWFKGTLQRTGKTGLFPGSFV 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.

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|...
gi 1720432874 129 IYPYSPQNDDELELVPGDFIfmSPMEQtsTSEGWIYGTSLTTGCSGLLPENYI 181
Cdd:cd11918     7 VYQYRPQNEDELELREGDRV--DVMQQ--CDDGWFVGVSRRTQKFGTFPGNYV 55

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.

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gi 1720432874 127 QVIYPYSPQNDDELELVPGDFIfmspMEQTSTSEGWIYGTSLTTGCSGLLPENYI 181
Cdd:cd11934     6 RAVYDYNAADEDEVSFQDGDTI----VNVQQIDDGWMYGTVERTGDTGMLPANYV 56

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.

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gi 1720432874 127 QVIYPYSPQNDDELELVPGDFI-FMSPMEqtstsEGWIYGTslTTGCSGLLPENYIT 182
Cdd:cd11874     3 KVLFSYTPQNEDELELKVGDTIeVLGEVE-----EGWWEGK--LNGKVGVFPSNFVK 52

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.

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gi 1720432874  124 ETLQVIYPYSPQNDDELELVPGDFIFMspMEQtsTSEGWIYGTsLTTGCSGLLPENYIT 182
Cdd:smart00326   3 PQVRALYDYTAQDPDELSFKKGDIITV--LEK--SDDGWWKGR-LGRGKEGLFPSNYVE 56

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.

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gi 1720432874 127 QVIYPYSPQNDDELELVPGDFIFMSpmeqTSTSEGWIYGTSLTTGCSGLLPENY 180
Cdd:cd11793     3 QCVHAYTAQQPDELTLEEGDVVNVL----RKMPDGWYEGERLRDGERGWFPSSY 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.

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gi 1720432874 129 IYPYSPQNDDELELVPGDFIFMSPMeqtsTSEGWIYGTslTTGCSGLLPENYIT 182
Cdd:cd11772     5 LYDYEAQHPDELSFEEGDLLYISDK----SDPNWWKAT--CGGKTGLIPSNYVE 52

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.

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gi 1720432874 127 QVIYPYSPQNDDELELVPGDFI-FMSPMEqtstsEGWIYGtsLTTGCSGLLPENYI 181
Cdd:cd12055     3 QVAFSYLPQNEDELELKVGDIIeVVGEVE-----EGWWEG--VLNGKTGMFPSNFI 51

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.

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gi 1720432874 125 TLQVIYPYSPQNDDELELVPGDfiFMSPMEQTSTSEGWiYGTSLTTGCSGLLPENYIT 182
Cdd:cd11904     2 VVQALYPFSSSNDEELNFEKGE--VMDVIEKPENDPEW-WKCRKANGQVGLVPKNYVT 56

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.

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gi 1720432874 127 QVIYPYSPQNDDELELVPGDFIfmspMEQTSTSEGWIYGTSlTTGCSGLLPENYI 181
Cdd:cd11962     3 VVLYDYEKDEDNEIELVEGEIV----TNIEMVDEDWWMGTN-SKGESGLFPSNYV 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.

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gi 1720432874 129 IYPYSPQNDDELELVPGDFIFMSPMEqtstSEGWIYGtSLtTGCSGLLPENYI 181
Cdd:cd11823     5 LYSYTANREDELSLQPGDIIEVHEKQ----DDGWWLG-EL-NGKKGIFPATYV 51

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.

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gi 1720432874 125 TLQVIYPYSPQNDDELELVPGDFIfmspmEQTSTSE----GWIYGTSLTTGCSGLLPENY 180
Cdd:cd11886     1 LLIVIHDFNARSEDELTLKPGDKI-----ELIEDDEefgdGWYLGRNLRTGETGLFPVVF 55

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.

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gi 1720432874 129 IYPYSPQNDDELELVPGDFIFMSPMEqtsTSEGWIYGTSLTTGCSGLLPENY 180
Cdd:cd11878     5 LYDYRAQTPGELSFSKGDFFHVIGEE---DQGEWYEATNPVTGKRGLVPKSY 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.

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gi 1720432874 130 YPYSPQNDDELELVPGDFIFMSPMEQTstseGWIYGTslTTGCSGLLPENYI 181
Cdd:cd12060     8 FNFKQTNEDELSVCKGDIIYVTRVEEG----GWWEGT--LNGKTGWFPSNYV 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.

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gi 1720432874 127 QVIYPYSPQNDDELELVPGDFIFMSpMEQTStseGWIYGTslTTGCSGLLPENYITK 183
Cdd:cd11827     3 KALYAYDAQDTDELSFNEGDIIEIL-KEDPS---GWWTGR--LRGKEGLFPGNYVEK 53

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.

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gi 1720432874 127 QVI--YPYSPQNDDELELVPGDFI-FMSPMEQTstsegWIYGTslTTGCSGLLPENYIT 182
Cdd:cd11840     1 QVIalFPYTAQNEDELSFQKGDIInVLSKDDPD-----WWRGE--LNGQTGLFPSNYVE 52

Src Homology 3 domain of Bridging integrator 1 (Bin1), also called Amphiphysin-2; Bin1 isoforms are localized in many different tissues and may function in intracellular vesicle trafficking. It plays a role in the organization and maintenance of the T-tubule network in skeletal muscle. Mutations in Bin1 are associated with autosomal recessive centronuclear myopathy. Bin1 contains an N-terminal BAR domain with an additional N-terminal amphipathic helix (an N-BAR) and a C-terminal SH3 domain. The SH3 domain of Bin1 forms transient complexes with actin, myosin filaments, and CDK5, to facilitate sarcomere organization and myofiber maturation. It also binds dynamin and prevents its self-assembly. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

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gi 1720432874 126 LQVIYPYSPQNDDELELVPGDFIFMSPMEQTSTS-EGWIYGTSLT--------TGCSGLLPENYITK 183
Cdd:cd12139     5 VQAQHDYTATDTDELQLKAGDVVLVIPFQNPEEQdEGWLMGVKESdwnqhkklEKCRGVFPENFTER 71

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.

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gi 1720432874 129 IYPYSPQNDDELELVPGDFIfmSPMEQtsTSEGWIYGTSlTTGCSGLLPENYIT 182
Cdd:cd11960     5 LYDYQAADDTEISFDPGDII--TDIEQ--IDEGWWRGTG-PDGTYGLFPANYVE 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.

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gi 1720432874 129 IYPYSPQNDDELELVPGDFIFMSpmeqTSTSEGWIYGTSltTGCSGLLPENYI 181
Cdd:cd11971     5 IYDYSKDKDDELSFMEGAIIYVI----KKNDDGWYEGVC--NGVTGLFPGNYV 51