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Conserved domains on  [gi|32455248|ref|NP_852664|]
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phosphatidylinositol 3-kinase regulatory subunit alpha isoform 1 [Homo sapiens]

Protein Classification

SH3 domain-containing protein( domain architecture ID 10186046)

Src Homology 3 (SH3) domain-containing protein plays versatile and diverse roles 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

Graphical summary

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List of domain hits

Name Accession Description Interval E-value
RhoGAP_p85 cd04388
RhoGAP_p85: RhoGAP (GTPase-activator protein [GAP] for Rho-like small GTPases) domain present ...
114-302 2.38e-122

RhoGAP_p85: RhoGAP (GTPase-activator protein [GAP] for Rho-like small GTPases) domain present in the p85 isoforms of the regulatory subunit of the class IA PI3K (phosphatidylinositol 3'-kinase). This domain is also called Bcr (breakpoint cluster region protein) homology (BH) domain. Class IA PI3Ks are heterodimers, containing a regulatory subunit (p85) and a catalytic subunit (p110) and are activated by growth factor receptor tyrosine kinases (RTKs); this activation is mediated by the p85 subunit. p85 isoforms, alpha and beta, contain a C-terminal p110-binding domain flanked by two SH2 domains, an N-terminal SH3 domain, and a RhoGAP domain flanked by two proline-rich regions. Small GTPases cluster into distinct families, and all act as molecular switches, active in their GTP-bound form but inactive when GDP-bound. The Rho family of GTPases activates effectors involved in a wide variety of developmental processes, including regulation of cytoskeleton formation, cell proliferation and the JNK signaling pathway. GTPases generally have a low intrinsic GTPase hydrolytic activity but there are family-specific groups of GAPs that enhance the rate of GTP hydrolysis by several orders of magnitude.


:

Pssm-ID: 239853  Cd Length: 200  Bit Score: 363.42  E-value: 2.38e-122
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 32455248 114 TLPDLAEQFAPPDIAPPLLIKLVEAIEKKGLECSTLYRTQSSSNLAELRQLLDCDTPSVDLEMIDVHVLADAFKRYLLDL 193
Cdd:cd04388   1 TLPDLTEQFSPPDVAPPLLIKLVEAIEKKGLESSTLYRTQSSSSLTELRQILDCDAASVDLEQFDVAALADALKRYLLDL 80
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 32455248 194 PNPVIPAAVYSEMISLAPEVQSSEEYIQLLKKLIRSPSIPHQYWLTLQYLLKHFFKLSQTSSKNLLNARVLSEIFSPMLF 273
Cdd:cd04388  81 PNPVIPAPVYSEMISRAQEVQSSDEYAQLLRKLIRSPNLPHQYWLTLQYLLKHFFRLCQSSSKNLLSARALAEIFSPLLF 160
                       170       180
                ....*....|....*....|....*....
gi 32455248 274 RFSAASSDNTENLIKVIEILISTEWNERQ 302
Cdd:cd04388 161 RFQPASSDSPEFHIRIIEVLITSEWNERQ 189
iSH2_PIK3R1 cd12924
Inter-Src homology 2 (iSH2) helical domain of Class IA Phosphoinositide 3-kinase Regulatory ...
440-600 6.99e-107

Inter-Src homology 2 (iSH2) helical domain of Class IA Phosphoinositide 3-kinase Regulatory subunit 1, PIK3R1, also called p85alpha; PI3Ks catalyze the transfer of the gamma-phosphoryl group from ATP to the 3-hydroxyl of the inositol ring of D-myo-phosphatidylinositol (PtdIns) or its derivatives. They play an important role in a variety of fundamental cellular processes, including cell motility, the Ras pathway, vesicle trafficking and secretion, immune cell activation and apoptosis. They are classified according to their substrate specificity, regulation, and domain structure. Class IA PI3Ks are heterodimers of a p110 catalytic (C) subunit and a p85-related regulatory (R) subunit. The R subunit down-regulates PI3K basal activity, stabilizes the C subunit, and plays a role in the activation downstream of tyrosine kinases. All R subunits contain two SH2 domains that flank an intervening helical domain (iSH2), which binds to the N-terminal adaptor-binding domain (ABD) of the catalytic subunit. In addition, p85alpha, also called PIK3R1, contains N-terminal SH3 and GAP domains. p85alpha carry functions independent of its PI3K regulatory role. It can independently stimulate signaling pathways involved in cytoskeletal rearrangements. Insulin-sensitive tissues express splice variants of the PIK3R1 gene, p50alpha and p55alpha, which may play important roles in insulin signaling during lipid and glucose metabolism. Mice deficient with PIK3R1 die perinatally, indicating its importance in development.


:

Pssm-ID: 214017 [Multi-domain]  Cd Length: 161  Bit Score: 322.03  E-value: 6.99e-107
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 32455248 440 DNIEAVGKKLHEYNTQFQEKSREYDRLYEEYTRTSQEIQMKRTAIEAFNETIKIFEEQCQTQERYSKEYIEKFKREGNEK 519
Cdd:cd12924   1 DNIEAVGKKLHEYNTQFQEKSREYDRLYEEYTRTSQEIQMKRTAIEAFNETIKIFEEQCQTQERYSKEYIEKFKREGNEK 80
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 32455248 520 EIQRIMHNYDKLKSRISEIIDSRRRLEEDLKKQAAEYREIDKRMNSIKPDLIQLRKTRDQYLMWLTQKGVRQKKLNEWLG 599
Cdd:cd12924  81 EIQRIMHNYEKLKSRISEIVDSRRRLEEDLKKQAAEYREIDKRMNSIKPDLIQLRKTRDQYLMWLTQKGVRQKKLNEWLG 160

                .
gi 32455248 600 N 600
Cdd:cd12924 161 N 161
SH2_cSH2_p85_like cd09930
C-terminal Src homology 2 (cSH2) domain found in p85; Phosphoinositide 3-kinases (PI3Ks) are ...
617-720 5.68e-73

C-terminal Src homology 2 (cSH2) domain found in p85; Phosphoinositide 3-kinases (PI3Ks) are essential for cell growth, migration, and survival. p110, the catalytic subunit, is composed of an adaptor-binding domain, a Ras-binding domain, a C2 domain, a helical domain, and a kinase domain. The regulatory unit is called p85 and is composed of an SH3 domain, a RhoGap domain, a N-terminal SH2 (nSH2) domain, a inter SH2 (iSH2) domain, and C-terminal (cSH2) domain. There are 2 inhibitory interactions between p110alpha and p85 of P13K: 1) p85 nSH2 domain with the C2, helical, and kinase domains of p110alpha and 2) p85 iSH2 domain with C2 domain of p110alpha. There are 3 inhibitory interactions between p110beta and p85 of P13K: 1) p85 nSH2 domain with the C2, helical, and kinase domains of p110beta, 2) p85 iSH2 domain with C2 domain of p110alpha, and 3) p85 cSH2 domain with the kinase domain of p110alpha. It is interesting to note that p110beta is oncogenic as a wild type protein while p110alpha lacks this ability. One explanation is the idea that the regulation of p110beta by p85 is unique because of the addition of inhibitory contacts from the cSH2 domain and the loss of contacts in the iSH2 domain. In general SH2 domains are involved in signal transduction. They typically bind pTyr-containing ligands via two surface pockets, a pTyr and hydrophobic binding pocket, allowing proteins with SH2 domains to localize to tyrosine phosphorylated sites.


:

Pssm-ID: 198184  Cd Length: 104  Bit Score: 231.53  E-value: 5.68e-73
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 32455248 617 PHHDEKTWNVGSSNRNKAENLLRGKRDGTFLVRESSKQGCYACSVVVDGEVKHCVINKTATGYGFAEPYNLYSSLKELVL 696
Cdd:cd09930   1 PHHDERTWLVGDINRTQAEELLRGKPDGTFLIRESSTQGCYACSVVCNGEVKHCVIYKTETGYGFAEPYNLYESLKELVL 80
                        90       100
                ....*....|....*....|....
gi 32455248 697 HYQHTSLVQHNDSLNVTLAYPVYA 720
Cdd:cd09930  81 HYAHNSLEQHNDSLTVTLAYPVLA 104
SH2_nSH2_p85_like cd09942
N-terminal Src homology 2 (nSH2) domain found in p85; Phosphoinositide 3-kinases (PI3Ks) are ...
325-435 7.79e-72

N-terminal Src homology 2 (nSH2) domain found in p85; Phosphoinositide 3-kinases (PI3Ks) are essential for cell growth, migration, and survival. p110, the catalytic subunit, is composed of an adaptor-binding domain, a Ras-binding domain, a C2 domain, a helical domain, and a kinase domain. The regulatory unit is called p85 and is composed of an SH3 domain, a RhoGap domain, a N-terminal SH2 (nSH2) domain, an internal SH2 (iSH2) domain, and C-terminal (cSH2) domain. There are 2 inhibitory interactions between p110alpha and p85 of P13K: (1) p85 nSH2 domain with the C2, helical, and kinase domains of p110alpha and (2) p85 iSH2 domain with C2 domain of p110alpha. There are 3 inhibitory interactions between p110beta and p85 of P13K: (1) p85 nSH2 domain with the C2, helical, and kinase domains of p110beta, (2) p85 iSH2 domain with C2 domain of p110alpha, and (3) p85 cSH2 domain with the kinase domain of p110alpha. It is interesting to note that p110beta is oncogenic as a wild type protein while p110alpha lacks this ability. One explanation is the idea that the regulation of p110beta by p85 is unique because of the addition of inhibitory contacts from the cSH2 domain and the loss of contacts in the iSH2 domain. In general SH2 domains are involved in signal transduction. They typically bind pTyr-containing ligands via two surface pockets, a pTyr and hydrophobic binding pocket, allowing proteins with SH2 domains to localize to tyrosine phosphorylated sites.


:

Pssm-ID: 198195  Cd Length: 110  Bit Score: 228.75  E-value: 7.79e-72
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 32455248 325 NMSLQDAEWYWGDISREEVNEKLRDTADGTFLVRDASTkMHGDYTLTLRKGGNNKLIKIFHRDGKYGFSDPLTFSSVVEL 404
Cdd:cd09942   1 PHSLQEAEWYWGDISREEVNEKMRDTPDGTFLVRDAST-MKGDYTLTLRKGGNNKLIKIFHRDGKYGFSDPLTFNSVVEL 79
                        90       100       110
                ....*....|....*....|....*....|.
gi 32455248 405 INHYRNESLAQYNPKLDVKLLYPVSKYQQDQ 435
Cdd:cd09942  80 INYYRNNSLAEYNRKLDVKLLYPVSRFQQDQ 110
SH3_PI3K_p85alpha cd11910
Src Homology 3 domain of the p85alpha regulatory subunit of Class IA Phosphatidylinositol ...
5-79 4.67e-49

Src Homology 3 domain of the p85alpha regulatory subunit of Class IA Phosphatidylinositol 3-kinases; Class I PI3Ks convert PtdIns(4,5)P2 to the critical second messenger PtdIns(3,4,5)P3. They are heterodimers and exist in multiple isoforms consisting of one catalytic subunit (out of four isoforms) and one of several regulatory subunits. Class IA PI3Ks associate with the p85 regulatory subunit family, which contains SH3, RhoGAP, and SH2 domains. The p85 subunits recruit the PI3K p110 catalytic subunit to the membrane, where p110 phosphorylates inositol lipids. Vertebrates harbor two p85 isoforms, called alpha and beta. In addition to regulating the p110 subunit, p85alpha interacts with activated FGFR3. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


:

Pssm-ID: 212843  Cd Length: 75  Bit Score: 166.23  E-value: 4.67e-49
                        10        20        30        40        50        60        70
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 32455248   5 GYQYRALYDYKKEREEDIDLHLGDILTVNKGSLVALGFSDGQEARPEEIGWLNGYNETTGERGDFPGTYVEYIGR 79
Cdd:cd11910   1 GYQYRALYDYKKEREEDIDLHLGDILTVNKGSLLALGFSEGQEARPEEIGWLNGYNETTGERGDFPGTYVEYIGR 75
 
Name Accession Description Interval E-value
RhoGAP_p85 cd04388
RhoGAP_p85: RhoGAP (GTPase-activator protein [GAP] for Rho-like small GTPases) domain present ...
114-302 2.38e-122

RhoGAP_p85: RhoGAP (GTPase-activator protein [GAP] for Rho-like small GTPases) domain present in the p85 isoforms of the regulatory subunit of the class IA PI3K (phosphatidylinositol 3'-kinase). This domain is also called Bcr (breakpoint cluster region protein) homology (BH) domain. Class IA PI3Ks are heterodimers, containing a regulatory subunit (p85) and a catalytic subunit (p110) and are activated by growth factor receptor tyrosine kinases (RTKs); this activation is mediated by the p85 subunit. p85 isoforms, alpha and beta, contain a C-terminal p110-binding domain flanked by two SH2 domains, an N-terminal SH3 domain, and a RhoGAP domain flanked by two proline-rich regions. Small GTPases cluster into distinct families, and all act as molecular switches, active in their GTP-bound form but inactive when GDP-bound. The Rho family of GTPases activates effectors involved in a wide variety of developmental processes, including regulation of cytoskeleton formation, cell proliferation and the JNK signaling pathway. GTPases generally have a low intrinsic GTPase hydrolytic activity but there are family-specific groups of GAPs that enhance the rate of GTP hydrolysis by several orders of magnitude.


Pssm-ID: 239853  Cd Length: 200  Bit Score: 363.42  E-value: 2.38e-122
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 32455248 114 TLPDLAEQFAPPDIAPPLLIKLVEAIEKKGLECSTLYRTQSSSNLAELRQLLDCDTPSVDLEMIDVHVLADAFKRYLLDL 193
Cdd:cd04388   1 TLPDLTEQFSPPDVAPPLLIKLVEAIEKKGLESSTLYRTQSSSSLTELRQILDCDAASVDLEQFDVAALADALKRYLLDL 80
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 32455248 194 PNPVIPAAVYSEMISLAPEVQSSEEYIQLLKKLIRSPSIPHQYWLTLQYLLKHFFKLSQTSSKNLLNARVLSEIFSPMLF 273
Cdd:cd04388  81 PNPVIPAPVYSEMISRAQEVQSSDEYAQLLRKLIRSPNLPHQYWLTLQYLLKHFFRLCQSSSKNLLSARALAEIFSPLLF 160
                       170       180
                ....*....|....*....|....*....
gi 32455248 274 RFSAASSDNTENLIKVIEILISTEWNERQ 302
Cdd:cd04388 161 RFQPASSDSPEFHIRIIEVLITSEWNERQ 189
iSH2_PIK3R1 cd12924
Inter-Src homology 2 (iSH2) helical domain of Class IA Phosphoinositide 3-kinase Regulatory ...
440-600 6.99e-107

Inter-Src homology 2 (iSH2) helical domain of Class IA Phosphoinositide 3-kinase Regulatory subunit 1, PIK3R1, also called p85alpha; PI3Ks catalyze the transfer of the gamma-phosphoryl group from ATP to the 3-hydroxyl of the inositol ring of D-myo-phosphatidylinositol (PtdIns) or its derivatives. They play an important role in a variety of fundamental cellular processes, including cell motility, the Ras pathway, vesicle trafficking and secretion, immune cell activation and apoptosis. They are classified according to their substrate specificity, regulation, and domain structure. Class IA PI3Ks are heterodimers of a p110 catalytic (C) subunit and a p85-related regulatory (R) subunit. The R subunit down-regulates PI3K basal activity, stabilizes the C subunit, and plays a role in the activation downstream of tyrosine kinases. All R subunits contain two SH2 domains that flank an intervening helical domain (iSH2), which binds to the N-terminal adaptor-binding domain (ABD) of the catalytic subunit. In addition, p85alpha, also called PIK3R1, contains N-terminal SH3 and GAP domains. p85alpha carry functions independent of its PI3K regulatory role. It can independently stimulate signaling pathways involved in cytoskeletal rearrangements. Insulin-sensitive tissues express splice variants of the PIK3R1 gene, p50alpha and p55alpha, which may play important roles in insulin signaling during lipid and glucose metabolism. Mice deficient with PIK3R1 die perinatally, indicating its importance in development.


Pssm-ID: 214017 [Multi-domain]  Cd Length: 161  Bit Score: 322.03  E-value: 6.99e-107
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 32455248 440 DNIEAVGKKLHEYNTQFQEKSREYDRLYEEYTRTSQEIQMKRTAIEAFNETIKIFEEQCQTQERYSKEYIEKFKREGNEK 519
Cdd:cd12924   1 DNIEAVGKKLHEYNTQFQEKSREYDRLYEEYTRTSQEIQMKRTAIEAFNETIKIFEEQCQTQERYSKEYIEKFKREGNEK 80
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 32455248 520 EIQRIMHNYDKLKSRISEIIDSRRRLEEDLKKQAAEYREIDKRMNSIKPDLIQLRKTRDQYLMWLTQKGVRQKKLNEWLG 599
Cdd:cd12924  81 EIQRIMHNYEKLKSRISEIVDSRRRLEEDLKKQAAEYREIDKRMNSIKPDLIQLRKTRDQYLMWLTQKGVRQKKLNEWLG 160

                .
gi 32455248 600 N 600
Cdd:cd12924 161 N 161
PI3K_P85_iSH2 pfam16454
Phosphatidylinositol 3-kinase regulatory subunit P85 inter-SH2 domain; This domain is found ...
431-599 8.11e-79

Phosphatidylinositol 3-kinase regulatory subunit P85 inter-SH2 domain; This domain is found between the two SH2 domains in phosphatidylinositol 3-kinase regulatory subunit P85. It forms a complex with the adaptor-binding domain of phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha.


Pssm-ID: 465121 [Multi-domain]  Cd Length: 161  Bit Score: 249.11  E-value: 8.11e-79
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 32455248   431 YQQDQVVKEDNIEAVGKKLHEYNTQFQEKSREYDRLYEEYTRTSQEIQMKRTAIEAFNETIKIFEEQCQTQERYSKEYie 510
Cdd:pfam16454   1 QQEDEVVKEDDIEAVGKKLIEIHKQYLEKSREYDRLYEEYNKTSQEIQMKRQALEAFNEAIKMFEEQIKLQERFSKEA-- 78
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 32455248   511 kfkregNEKEIQRIMHNYDKLKSRISEIIDSRRRLEEDLKKQAAEYREIDKRMNSIKPDLIQLRKTRDQYLMWLTQKGVR 590
Cdd:pfam16454  79 ------QPHEIERLLENYELLKSRLKELHDSKEQLEEDLKTQKEYNRELEREMNSLKPELIQLRKQKDQYLEWLKRKGVT 152

                  ....*....
gi 32455248   591 QKKLNEWLG 599
Cdd:pfam16454 153 QEQINAWLG 161
SH2_cSH2_p85_like cd09930
C-terminal Src homology 2 (cSH2) domain found in p85; Phosphoinositide 3-kinases (PI3Ks) are ...
617-720 5.68e-73

C-terminal Src homology 2 (cSH2) domain found in p85; Phosphoinositide 3-kinases (PI3Ks) are essential for cell growth, migration, and survival. p110, the catalytic subunit, is composed of an adaptor-binding domain, a Ras-binding domain, a C2 domain, a helical domain, and a kinase domain. The regulatory unit is called p85 and is composed of an SH3 domain, a RhoGap domain, a N-terminal SH2 (nSH2) domain, a inter SH2 (iSH2) domain, and C-terminal (cSH2) domain. There are 2 inhibitory interactions between p110alpha and p85 of P13K: 1) p85 nSH2 domain with the C2, helical, and kinase domains of p110alpha and 2) p85 iSH2 domain with C2 domain of p110alpha. There are 3 inhibitory interactions between p110beta and p85 of P13K: 1) p85 nSH2 domain with the C2, helical, and kinase domains of p110beta, 2) p85 iSH2 domain with C2 domain of p110alpha, and 3) p85 cSH2 domain with the kinase domain of p110alpha. It is interesting to note that p110beta is oncogenic as a wild type protein while p110alpha lacks this ability. One explanation is the idea that the regulation of p110beta by p85 is unique because of the addition of inhibitory contacts from the cSH2 domain and the loss of contacts in the iSH2 domain. In general SH2 domains are involved in signal transduction. They typically bind pTyr-containing ligands via two surface pockets, a pTyr and hydrophobic binding pocket, allowing proteins with SH2 domains to localize to tyrosine phosphorylated sites.


Pssm-ID: 198184  Cd Length: 104  Bit Score: 231.53  E-value: 5.68e-73
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 32455248 617 PHHDEKTWNVGSSNRNKAENLLRGKRDGTFLVRESSKQGCYACSVVVDGEVKHCVINKTATGYGFAEPYNLYSSLKELVL 696
Cdd:cd09930   1 PHHDERTWLVGDINRTQAEELLRGKPDGTFLIRESSTQGCYACSVVCNGEVKHCVIYKTETGYGFAEPYNLYESLKELVL 80
                        90       100
                ....*....|....*....|....
gi 32455248 697 HYQHTSLVQHNDSLNVTLAYPVYA 720
Cdd:cd09930  81 HYAHNSLEQHNDSLTVTLAYPVLA 104
SH2_nSH2_p85_like cd09942
N-terminal Src homology 2 (nSH2) domain found in p85; Phosphoinositide 3-kinases (PI3Ks) are ...
325-435 7.79e-72

N-terminal Src homology 2 (nSH2) domain found in p85; Phosphoinositide 3-kinases (PI3Ks) are essential for cell growth, migration, and survival. p110, the catalytic subunit, is composed of an adaptor-binding domain, a Ras-binding domain, a C2 domain, a helical domain, and a kinase domain. The regulatory unit is called p85 and is composed of an SH3 domain, a RhoGap domain, a N-terminal SH2 (nSH2) domain, an internal SH2 (iSH2) domain, and C-terminal (cSH2) domain. There are 2 inhibitory interactions between p110alpha and p85 of P13K: (1) p85 nSH2 domain with the C2, helical, and kinase domains of p110alpha and (2) p85 iSH2 domain with C2 domain of p110alpha. There are 3 inhibitory interactions between p110beta and p85 of P13K: (1) p85 nSH2 domain with the C2, helical, and kinase domains of p110beta, (2) p85 iSH2 domain with C2 domain of p110alpha, and (3) p85 cSH2 domain with the kinase domain of p110alpha. It is interesting to note that p110beta is oncogenic as a wild type protein while p110alpha lacks this ability. One explanation is the idea that the regulation of p110beta by p85 is unique because of the addition of inhibitory contacts from the cSH2 domain and the loss of contacts in the iSH2 domain. In general SH2 domains are involved in signal transduction. They typically bind pTyr-containing ligands via two surface pockets, a pTyr and hydrophobic binding pocket, allowing proteins with SH2 domains to localize to tyrosine phosphorylated sites.


Pssm-ID: 198195  Cd Length: 110  Bit Score: 228.75  E-value: 7.79e-72
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 32455248 325 NMSLQDAEWYWGDISREEVNEKLRDTADGTFLVRDASTkMHGDYTLTLRKGGNNKLIKIFHRDGKYGFSDPLTFSSVVEL 404
Cdd:cd09942   1 PHSLQEAEWYWGDISREEVNEKMRDTPDGTFLVRDAST-MKGDYTLTLRKGGNNKLIKIFHRDGKYGFSDPLTFNSVVEL 79
                        90       100       110
                ....*....|....*....|....*....|.
gi 32455248 405 INHYRNESLAQYNPKLDVKLLYPVSKYQQDQ 435
Cdd:cd09942  80 INYYRNNSLAEYNRKLDVKLLYPVSRFQQDQ 110
SH3_PI3K_p85alpha cd11910
Src Homology 3 domain of the p85alpha regulatory subunit of Class IA Phosphatidylinositol ...
5-79 4.67e-49

Src Homology 3 domain of the p85alpha regulatory subunit of Class IA Phosphatidylinositol 3-kinases; Class I PI3Ks convert PtdIns(4,5)P2 to the critical second messenger PtdIns(3,4,5)P3. They are heterodimers and exist in multiple isoforms consisting of one catalytic subunit (out of four isoforms) and one of several regulatory subunits. Class IA PI3Ks associate with the p85 regulatory subunit family, which contains SH3, RhoGAP, and SH2 domains. The p85 subunits recruit the PI3K p110 catalytic subunit to the membrane, where p110 phosphorylates inositol lipids. Vertebrates harbor two p85 isoforms, called alpha and beta. In addition to regulating the p110 subunit, p85alpha interacts with activated FGFR3. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 212843  Cd Length: 75  Bit Score: 166.23  E-value: 4.67e-49
                        10        20        30        40        50        60        70
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 32455248   5 GYQYRALYDYKKEREEDIDLHLGDILTVNKGSLVALGFSDGQEARPEEIGWLNGYNETTGERGDFPGTYVEYIGR 79
Cdd:cd11910   1 GYQYRALYDYKKEREEDIDLHLGDILTVNKGSLLALGFSEGQEARPEEIGWLNGYNETTGERGDFPGTYVEYIGR 75
RhoGAP smart00324
GTPase-activator protein for Rho-like GTPases; GTPase activator proteins towards Rho/Rac ...
129-295 1.77e-41

GTPase-activator protein for Rho-like GTPases; GTPase activator proteins towards Rho/Rac/Cdc42-like small GTPases. etter domain limits and outliers.


Pssm-ID: 214618  Cd Length: 174  Bit Score: 148.95  E-value: 1.77e-41
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 32455248    129 PPLLIKLVEAIEKKGLECSTLYRTQ-SSSNLAELRQLLDCDT-PSVDLEMIDVHVLADAFKRYLLDLPNPVIPAAVYSEM 206
Cdd:smart00324   4 PIIVEKCIEYLEKRGLDTEGIYRVSgSKSRVKELRDAFDSGPdPDLDLSEYDVHDVAGLLKLFLRELPEPLITYELYEEF 83
                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 32455248    207 ISLApEVQSSEEYIQLLKKLIRSpsIPHQYWLTLQYLLKHFFKLSQTSSKNLLNARVLSEIFSPMLFRFSA---ASSDNT 283
Cdd:smart00324  84 IEAA-KLEDETERLRALRELLSL--LPPANRATLRYLLAHLNRVAEHSEENKMTARNLAIVFGPTLLRPPDgevASLKDI 160
                          170
                   ....*....|..
gi 32455248    284 ENLIKVIEILIS 295
Cdd:smart00324 161 RHQNTVIEFLIE 172
RhoGAP pfam00620
RhoGAP domain; GTPase activator proteins towards Rho/Rac/Cdc42-like small GTPases.
129-274 1.28e-35

RhoGAP domain; GTPase activator proteins towards Rho/Rac/Cdc42-like small GTPases.


Pssm-ID: 459875  Cd Length: 148  Bit Score: 131.51  E-value: 1.28e-35
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 32455248   129 PPLLIKLVEAIEKKGLECSTLYRTQ-SSSNLAELRQLLDCD-TPSVDLEMIDVHVLADAFKRYLLDLPNPVIPAAVYSEM 206
Cdd:pfam00620   1 PLIVRKCVEYLEKRGLDTEGIFRVSgSASRIKELREAFDRGpDVDLDLEEEDVHVVASLLKLFLRELPEPLLTFELYEEF 80
                          90       100       110       120       130       140
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 32455248   207 ISLApEVQSSEEYIQLLKKLIRspSIPHQYWLTLQYLLKHFFKLSQTSSKNLLNARVLSEIFSPMLFR 274
Cdd:pfam00620  81 IEAA-KLPDEEERLEALRELLR--KLPPANRDTLRYLLAHLNRVAQNSDVNKMNAHNLAIVFGPTLLR 145
SH2 smart00252
Src homology 2 domains; Src homology 2 domains bind phosphotyrosine-containing polypeptides ...
332-413 1.93e-24

Src homology 2 domains; Src homology 2 domains bind phosphotyrosine-containing polypeptides via 2 surface pockets. Specificity is provided via interaction with residues that are distinct from the phosphotyrosine. Only a single occurrence of a SH2 domain has been found in S. cerevisiae.


Pssm-ID: 214585 [Multi-domain]  Cd Length: 84  Bit Score: 97.30  E-value: 1.93e-24
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 32455248    332 EWYWGDISREEVNEKLRDTADGTFLVRDaSTKMHGDYTLTLRKGGNNKLIKIFH-RDGKYGFSDPLTFSSVVELINHYRN 410
Cdd:smart00252   2 PWYHGFISREEAEKLLKNEGDGDFLVRD-SESSPGDYVLSVRVKGKVKHYRIRRnEDGKFYLEGGRKFPSLVELVEHYQK 80

                   ...
gi 32455248    411 ESL 413
Cdd:smart00252  81 NSL 83
SH2 pfam00017
SH2 domain;
624-698 1.54e-22

SH2 domain;


Pssm-ID: 425423 [Multi-domain]  Cd Length: 77  Bit Score: 91.89  E-value: 1.54e-22
                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 32455248   624 WNVGSSNRNKAENLLR-GKRDGTFLVRES-SKQGCYACSVVVDGEVKHCVINKTATG--YGFAEPYnlYSSLKELVLHY 698
Cdd:pfam00017   1 WYHGKISRQEAERLLLnGKPDGTFLVRESeSTPGGYTLSVRDDGKVKHYKIQSTDNGgyYISGGVK--FSSLAELVEHY 77
SH2 smart00252
Src homology 2 domains; Src homology 2 domains bind phosphotyrosine-containing polypeptides ...
624-704 9.41e-21

Src homology 2 domains; Src homology 2 domains bind phosphotyrosine-containing polypeptides via 2 surface pockets. Specificity is provided via interaction with residues that are distinct from the phosphotyrosine. Only a single occurrence of a SH2 domain has been found in S. cerevisiae.


Pssm-ID: 214585 [Multi-domain]  Cd Length: 84  Bit Score: 86.90  E-value: 9.41e-21
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 32455248    624 WNVGSSNRNKAENLLRGKRDGTFLVRES-SKQGCYACSVVVDGEVKHCVINKTATGYGFAEPYNLYSSLKELVLHYQHTS 702
Cdd:smart00252   3 WYHGFISREEAEKLLKNEGDGDFLVRDSeSSPGDYVLSVRVKGKVKHYRIRRNEDGKFYLEGGRKFPSLVELVEHYQKNS 82

                   ..
gi 32455248    703 LV 704
Cdd:smart00252  83 LG 84
SH2 pfam00017
SH2 domain;
333-408 1.08e-19

SH2 domain;


Pssm-ID: 425423 [Multi-domain]  Cd Length: 77  Bit Score: 83.80  E-value: 1.08e-19
                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 32455248   333 WYWGDISREEVNEKLRDT-ADGTFLVRDASTKMhGDYTLTLRKGGNNKLIKI-FHRDGKYGFSDPLTFSSVVELINHY 408
Cdd:pfam00017   1 WYHGKISRQEAERLLLNGkPDGTFLVRESESTP-GGYTLSVRDDGKVKHYKIqSTDNGGYYISGGVKFSSLAELVEHY 77
SH3 smart00326
Src homology 3 domains; Src homology 3 (SH3) domains bind to target proteins through sequences ...
4-75 4.83e-09

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: 52.54  E-value: 4.83e-09
                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|..
gi 32455248      4 EGYQYRALYDYKKEREEDIDLHLGDILTVnkgslvaLGFSDGqearpeeiGWLNGYNEtTGERGDFPGTYVE 75
Cdd:smart00326   1 EGPQVRALYDYTAQDPDELSFKKGDIITV-------LEKSDD--------GWWKGRLG-RGKEGLFPSNYVE 56
SMC_prok_B TIGR02168
chromosome segregation protein SMC, common bacterial type; SMC (structural maintenance of ...
428-576 3.26e-05

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: 47.36  E-value: 3.26e-05
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 32455248    428 VSKYQQDQVVKEDNIEAVGKKLHEYNTQFQEKSREYDRLYEEYTRTSQEI-------QMKRTAIEAFNETIKIFEEQCQT 500
Cdd:TIGR02168  248 LKEAEEELEELTAELQELEEKLEELRLEVSELEEEIEELQKELYALANEIsrleqqkQILRERLANLERQLEELEAQLEE 327
                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 32455248    501 QERYSKEYIEKFKRegNEKEIQRIMHNYDKLKSRISE----IIDSRRR---LEEDLKKQAAEYREIDKRMNSIKPDLIQL 573
Cdd:TIGR02168  328 LESKLDELAEELAE--LEEKLEELKEELESLEAELEEleaeLEELESRleeLEEQLETLRSKVAQLELQIASLNNEIERL 405

                   ...
gi 32455248    574 RKT 576
Cdd:TIGR02168  406 EAR 408
DR0291 COG1579
Predicted nucleic acid-binding protein DR0291, contains C4-type Zn-ribbon domain [General ...
448-579 3.34e-05

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: 46.07  E-value: 3.34e-05
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 32455248 448 KLHEYNTQFQEKSREYDRLYEEYTRTSQEIQMKRTAIEAFNETIKIFEEQCQTQERYSKEY---IEKFKRE----GNEKE 520
Cdd:COG1579  11 DLQELDSELDRLEHRLKELPAELAELEDELAALEARLEAAKTELEDLEKEIKRLELEIEEVearIKKYEEQlgnvRNNKE 90
                        90       100       110       120       130
                ....*....|....*....|....*....|....*....|....*....|....*....
gi 32455248 521 IQRIMHNYDKLKSRISEIIDSRRRLEEDLKKQAAEYREIDKRMNSIKPDLIQLRKTRDQ 579
Cdd:COG1579  91 YEALQKEIESLKRRISDLEDEILELMERIEELEEELAELEAELAELEAELEEKKAELDE 149
PRK03918 PRK03918
DNA double-strand break repair ATPase Rad50;
430-580 9.71e-04

DNA double-strand break repair ATPase Rad50;


Pssm-ID: 235175 [Multi-domain]  Cd Length: 880  Bit Score: 42.74  E-value: 9.71e-04
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 32455248  430 KYQQDQVVKEDNIEavgKKLHEYNTQFQEKSREYDRLYEEYTRTSQEIQMKRTAIEAFNETIKIFEEQcqtqeRYSKEYI 509
Cdd:PRK03918 179 ERLEKFIKRTENIE---ELIKEKEKELEEVLREINEISSELPELREELEKLEKEVKELEELKEEIEEL-----EKELESL 250
                         90       100       110       120       130       140       150
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|.
gi 32455248  510 EKFKREGNEKeIQRIMHNYDKLKSRISEIIDSRRRLEEdLKKQAAEYREIDKRMNSIKPDLIQLRKTRDQY 580
Cdd:PRK03918 251 EGSKRKLEEK-IRELEERIEELKKEIEELEEKVKELKE-LKEKAEEYIKLSEFYEEYLDELREIEKRLSRL 319
SH3_1 pfam00018
SH3 domain; SH3 (Src homology 3) domains are often indicative of a protein involved in signal ...
9-70 3.06e-03

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: 36.03  E-value: 3.06e-03
                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|..
gi 32455248     9 RALYDYKKEREEDIDLHLGDILTVnkgslvaLGFSDGqearpeeiGWLNGYNeTTGERGDFP 70
Cdd:pfam00018   1 VALYDYTAQEPDELSFKKGDIIIV-------LEKSED--------GWWKGRN-KGGKEGLIP 46
 
Name Accession Description Interval E-value
RhoGAP_p85 cd04388
RhoGAP_p85: RhoGAP (GTPase-activator protein [GAP] for Rho-like small GTPases) domain present ...
114-302 2.38e-122

RhoGAP_p85: RhoGAP (GTPase-activator protein [GAP] for Rho-like small GTPases) domain present in the p85 isoforms of the regulatory subunit of the class IA PI3K (phosphatidylinositol 3'-kinase). This domain is also called Bcr (breakpoint cluster region protein) homology (BH) domain. Class IA PI3Ks are heterodimers, containing a regulatory subunit (p85) and a catalytic subunit (p110) and are activated by growth factor receptor tyrosine kinases (RTKs); this activation is mediated by the p85 subunit. p85 isoforms, alpha and beta, contain a C-terminal p110-binding domain flanked by two SH2 domains, an N-terminal SH3 domain, and a RhoGAP domain flanked by two proline-rich regions. Small GTPases cluster into distinct families, and all act as molecular switches, active in their GTP-bound form but inactive when GDP-bound. The Rho family of GTPases activates effectors involved in a wide variety of developmental processes, including regulation of cytoskeleton formation, cell proliferation and the JNK signaling pathway. GTPases generally have a low intrinsic GTPase hydrolytic activity but there are family-specific groups of GAPs that enhance the rate of GTP hydrolysis by several orders of magnitude.


Pssm-ID: 239853  Cd Length: 200  Bit Score: 363.42  E-value: 2.38e-122
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 32455248 114 TLPDLAEQFAPPDIAPPLLIKLVEAIEKKGLECSTLYRTQSSSNLAELRQLLDCDTPSVDLEMIDVHVLADAFKRYLLDL 193
Cdd:cd04388   1 TLPDLTEQFSPPDVAPPLLIKLVEAIEKKGLESSTLYRTQSSSSLTELRQILDCDAASVDLEQFDVAALADALKRYLLDL 80
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 32455248 194 PNPVIPAAVYSEMISLAPEVQSSEEYIQLLKKLIRSPSIPHQYWLTLQYLLKHFFKLSQTSSKNLLNARVLSEIFSPMLF 273
Cdd:cd04388  81 PNPVIPAPVYSEMISRAQEVQSSDEYAQLLRKLIRSPNLPHQYWLTLQYLLKHFFRLCQSSSKNLLSARALAEIFSPLLF 160
                       170       180
                ....*....|....*....|....*....
gi 32455248 274 RFSAASSDNTENLIKVIEILISTEWNERQ 302
Cdd:cd04388 161 RFQPASSDSPEFHIRIIEVLITSEWNERQ 189
iSH2_PIK3R1 cd12924
Inter-Src homology 2 (iSH2) helical domain of Class IA Phosphoinositide 3-kinase Regulatory ...
440-600 6.99e-107

Inter-Src homology 2 (iSH2) helical domain of Class IA Phosphoinositide 3-kinase Regulatory subunit 1, PIK3R1, also called p85alpha; PI3Ks catalyze the transfer of the gamma-phosphoryl group from ATP to the 3-hydroxyl of the inositol ring of D-myo-phosphatidylinositol (PtdIns) or its derivatives. They play an important role in a variety of fundamental cellular processes, including cell motility, the Ras pathway, vesicle trafficking and secretion, immune cell activation and apoptosis. They are classified according to their substrate specificity, regulation, and domain structure. Class IA PI3Ks are heterodimers of a p110 catalytic (C) subunit and a p85-related regulatory (R) subunit. The R subunit down-regulates PI3K basal activity, stabilizes the C subunit, and plays a role in the activation downstream of tyrosine kinases. All R subunits contain two SH2 domains that flank an intervening helical domain (iSH2), which binds to the N-terminal adaptor-binding domain (ABD) of the catalytic subunit. In addition, p85alpha, also called PIK3R1, contains N-terminal SH3 and GAP domains. p85alpha carry functions independent of its PI3K regulatory role. It can independently stimulate signaling pathways involved in cytoskeletal rearrangements. Insulin-sensitive tissues express splice variants of the PIK3R1 gene, p50alpha and p55alpha, which may play important roles in insulin signaling during lipid and glucose metabolism. Mice deficient with PIK3R1 die perinatally, indicating its importance in development.


Pssm-ID: 214017 [Multi-domain]  Cd Length: 161  Bit Score: 322.03  E-value: 6.99e-107
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 32455248 440 DNIEAVGKKLHEYNTQFQEKSREYDRLYEEYTRTSQEIQMKRTAIEAFNETIKIFEEQCQTQERYSKEYIEKFKREGNEK 519
Cdd:cd12924   1 DNIEAVGKKLHEYNTQFQEKSREYDRLYEEYTRTSQEIQMKRTAIEAFNETIKIFEEQCQTQERYSKEYIEKFKREGNEK 80
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 32455248 520 EIQRIMHNYDKLKSRISEIIDSRRRLEEDLKKQAAEYREIDKRMNSIKPDLIQLRKTRDQYLMWLTQKGVRQKKLNEWLG 599
Cdd:cd12924  81 EIQRIMHNYEKLKSRISEIVDSRRRLEEDLKKQAAEYREIDKRMNSIKPDLIQLRKTRDQYLMWLTQKGVRQKKLNEWLG 160

                .
gi 32455248 600 N 600
Cdd:cd12924 161 N 161
iSH2_PIK3R3 cd12925
Inter-Src homology 2 (iSH2) helical domain of Class IA Phosphoinositide 3-kinase Regulatory ...
440-599 8.56e-92

Inter-Src homology 2 (iSH2) helical domain of Class IA Phosphoinositide 3-kinase Regulatory subunit 3, PIK3R3, also called p55gamma; PI3Ks catalyze the transfer of the gamma-phosphoryl group from ATP to the 3-hydroxyl of the inositol ring of D-myo-phosphatidylinositol (PtdIns) or its derivatives. They play an important role in a variety of fundamental cellular processes, including cell motility, the Ras pathway, vesicle trafficking and secretion, immune cell activation, and apoptosis. They are classified according to their substrate specificity, regulation, and domain structure. Class IA PI3Ks are heterodimers of a p110 catalytic (C) subunit and a p85-related regulatory (R) subunit. The R subunit down-regulates PI3K basal activity, stabilizes the C subunit, and plays a role in the activation downstream of tyrosine kinases. All R subunits contain two SH2 domains that flank an intervening helical domain (iSH2), which binds to the N-terminal adaptor-binding domain (ABD) of the catalytic subunit. p55gamma, also called PIK3R3 or p55PIK, also contains a unique N-terminal 24-amino acid residue (N24) that interacts with cell cycle modulators to promote cell cycle progression.


Pssm-ID: 214018 [Multi-domain]  Cd Length: 161  Bit Score: 283.10  E-value: 8.56e-92
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 32455248 440 DNIEAVGKKLHEYNTQFQEKSREYDRLYEEYTRTSQEIQMKRTAIEAFNETIKIFEEQCQTQERYSKEYIEKFKREGNEK 519
Cdd:cd12925   1 DNIDAVGRKLQEYHSQYQEKSKEYDRLYEEYTKTSQEIQMKRTAIEAFNETIKIFEEQCHTQERYSKEYIERFRREGNEK 80
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 32455248 520 EIQRIMHNYDKLKSRISEIIDSRRRLEEDLKKQAAEYREIDKRMNSIKPDLIQLRKTRDQYLMWLTQKGVRQKKLNEWLG 599
Cdd:cd12925  81 EIERIMMNYEKLKSRLGEIHDSKMRLEQDLKTQALDNREIDKKMNSIKPDLIQLRKIRDQYLVWLNHKGVRQKRINDWLG 160
iSH2_PIK3R2 cd12926
Inter-Src homology 2 (iSH2) helical domain of Class IA Phosphoinositide 3-kinase Regulatory ...
440-599 1.75e-90

Inter-Src homology 2 (iSH2) helical domain of Class IA Phosphoinositide 3-kinase Regulatory subunit 2, PIK3R2, also called p85beta; PI3Ks catalyze the transfer of the gamma-phosphoryl group from ATP to the 3-hydroxyl of the inositol ring of D-myo-phosphatidylinositol (PtdIns) or its derivatives. They play an important role in a variety of fundamental cellular processes, including cell motility, the Ras pathway, vesicle trafficking and secretion, immune cell activation, and apoptosis. They are classified according to their substrate specificity, regulation, and domain structure. Class IA PI3Ks are heterodimers of a p110 catalytic (C) subunit and a p85-related regulatory (R) subunit. The R subunit down-regulates PI3K basal activity, stabilizes the C subunit, and plays a role in the activation downstream of tyrosine kinases. All R subunits contain two SH2 domains that flank an intervening helical domain (iSH2), which binds to the N-terminal adaptor-binding domain (ABD) of the catalytic subunit. p85beta, also called PIK3R2, contains N-terminal SH3 and GAP domains. It is expressed ubiquitously but at lower levels than p85alpha. Its expression is increased in breast and colon cancer, correlates with tumor progression, and enhanced invasion. During viral infection, the viral nonstructural (NS1) protein binds p85beta specifically, which leads to PI3K activation and the promotion of viral replication. Mice deficient with PIK3R2 develop normally and exhibit moderate metabolic and immunological defects.


Pssm-ID: 214019 [Multi-domain]  Cd Length: 161  Bit Score: 279.66  E-value: 1.75e-90
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 32455248 440 DNIEAVGKKLHEYNTQFQEKSREYDRLYEEYTRTSQEIQMKRTAIEAFNETIKIFEEQCQTQERYSKEYIEKFKREGNEK 519
Cdd:cd12926   1 DSVEAVGAQLKVYHQQYQDKSREYDQLYEEYTRTSQELQMKRTAIEAFNETIKIFEEQGQTQEKCSKEYLERFRREGNEK 80
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 32455248 520 EIQRIMHNYDKLKSRISEIIDSRRRLEEDLKKQAAEYREIDKRMNSIKPDLIQLRKTRDQYLMWLTQKGVRQKKLNEWLG 599
Cdd:cd12926  81 EMQRILLNSERLKSRIAEIHESRTKLEQDLRAQASDNREIDKRMNSLKPDLMQLRKIRDQYLVWLTQKGARQKKINEWLG 160
PI3K_P85_iSH2 pfam16454
Phosphatidylinositol 3-kinase regulatory subunit P85 inter-SH2 domain; This domain is found ...
431-599 8.11e-79

Phosphatidylinositol 3-kinase regulatory subunit P85 inter-SH2 domain; This domain is found between the two SH2 domains in phosphatidylinositol 3-kinase regulatory subunit P85. It forms a complex with the adaptor-binding domain of phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha.


Pssm-ID: 465121 [Multi-domain]  Cd Length: 161  Bit Score: 249.11  E-value: 8.11e-79
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 32455248   431 YQQDQVVKEDNIEAVGKKLHEYNTQFQEKSREYDRLYEEYTRTSQEIQMKRTAIEAFNETIKIFEEQCQTQERYSKEYie 510
Cdd:pfam16454   1 QQEDEVVKEDDIEAVGKKLIEIHKQYLEKSREYDRLYEEYNKTSQEIQMKRQALEAFNEAIKMFEEQIKLQERFSKEA-- 78
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 32455248   511 kfkregNEKEIQRIMHNYDKLKSRISEIIDSRRRLEEDLKKQAAEYREIDKRMNSIKPDLIQLRKTRDQYLMWLTQKGVR 590
Cdd:pfam16454  79 ------QPHEIERLLENYELLKSRLKELHDSKEQLEEDLKTQKEYNRELEREMNSLKPELIQLRKQKDQYLEWLKRKGVT 152

                  ....*....
gi 32455248   591 QKKLNEWLG 599
Cdd:pfam16454 153 QEQINAWLG 161
SH2_cSH2_p85_like cd09930
C-terminal Src homology 2 (cSH2) domain found in p85; Phosphoinositide 3-kinases (PI3Ks) are ...
617-720 5.68e-73

C-terminal Src homology 2 (cSH2) domain found in p85; Phosphoinositide 3-kinases (PI3Ks) are essential for cell growth, migration, and survival. p110, the catalytic subunit, is composed of an adaptor-binding domain, a Ras-binding domain, a C2 domain, a helical domain, and a kinase domain. The regulatory unit is called p85 and is composed of an SH3 domain, a RhoGap domain, a N-terminal SH2 (nSH2) domain, a inter SH2 (iSH2) domain, and C-terminal (cSH2) domain. There are 2 inhibitory interactions between p110alpha and p85 of P13K: 1) p85 nSH2 domain with the C2, helical, and kinase domains of p110alpha and 2) p85 iSH2 domain with C2 domain of p110alpha. There are 3 inhibitory interactions between p110beta and p85 of P13K: 1) p85 nSH2 domain with the C2, helical, and kinase domains of p110beta, 2) p85 iSH2 domain with C2 domain of p110alpha, and 3) p85 cSH2 domain with the kinase domain of p110alpha. It is interesting to note that p110beta is oncogenic as a wild type protein while p110alpha lacks this ability. One explanation is the idea that the regulation of p110beta by p85 is unique because of the addition of inhibitory contacts from the cSH2 domain and the loss of contacts in the iSH2 domain. In general SH2 domains are involved in signal transduction. They typically bind pTyr-containing ligands via two surface pockets, a pTyr and hydrophobic binding pocket, allowing proteins with SH2 domains to localize to tyrosine phosphorylated sites.


Pssm-ID: 198184  Cd Length: 104  Bit Score: 231.53  E-value: 5.68e-73
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 32455248 617 PHHDEKTWNVGSSNRNKAENLLRGKRDGTFLVRESSKQGCYACSVVVDGEVKHCVINKTATGYGFAEPYNLYSSLKELVL 696
Cdd:cd09930   1 PHHDERTWLVGDINRTQAEELLRGKPDGTFLIRESSTQGCYACSVVCNGEVKHCVIYKTETGYGFAEPYNLYESLKELVL 80
                        90       100
                ....*....|....*....|....
gi 32455248 697 HYQHTSLVQHNDSLNVTLAYPVYA 720
Cdd:cd09930  81 HYAHNSLEQHNDSLTVTLAYPVLA 104
SH2_nSH2_p85_like cd09942
N-terminal Src homology 2 (nSH2) domain found in p85; Phosphoinositide 3-kinases (PI3Ks) are ...
325-435 7.79e-72

N-terminal Src homology 2 (nSH2) domain found in p85; Phosphoinositide 3-kinases (PI3Ks) are essential for cell growth, migration, and survival. p110, the catalytic subunit, is composed of an adaptor-binding domain, a Ras-binding domain, a C2 domain, a helical domain, and a kinase domain. The regulatory unit is called p85 and is composed of an SH3 domain, a RhoGap domain, a N-terminal SH2 (nSH2) domain, an internal SH2 (iSH2) domain, and C-terminal (cSH2) domain. There are 2 inhibitory interactions between p110alpha and p85 of P13K: (1) p85 nSH2 domain with the C2, helical, and kinase domains of p110alpha and (2) p85 iSH2 domain with C2 domain of p110alpha. There are 3 inhibitory interactions between p110beta and p85 of P13K: (1) p85 nSH2 domain with the C2, helical, and kinase domains of p110beta, (2) p85 iSH2 domain with C2 domain of p110alpha, and (3) p85 cSH2 domain with the kinase domain of p110alpha. It is interesting to note that p110beta is oncogenic as a wild type protein while p110alpha lacks this ability. One explanation is the idea that the regulation of p110beta by p85 is unique because of the addition of inhibitory contacts from the cSH2 domain and the loss of contacts in the iSH2 domain. In general SH2 domains are involved in signal transduction. They typically bind pTyr-containing ligands via two surface pockets, a pTyr and hydrophobic binding pocket, allowing proteins with SH2 domains to localize to tyrosine phosphorylated sites.


Pssm-ID: 198195  Cd Length: 110  Bit Score: 228.75  E-value: 7.79e-72
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 32455248 325 NMSLQDAEWYWGDISREEVNEKLRDTADGTFLVRDASTkMHGDYTLTLRKGGNNKLIKIFHRDGKYGFSDPLTFSSVVEL 404
Cdd:cd09942   1 PHSLQEAEWYWGDISREEVNEKMRDTPDGTFLVRDAST-MKGDYTLTLRKGGNNKLIKIFHRDGKYGFSDPLTFNSVVEL 79
                        90       100       110
                ....*....|....*....|....*....|.
gi 32455248 405 INHYRNESLAQYNPKLDVKLLYPVSKYQQDQ 435
Cdd:cd09942  80 INYYRNNSLAEYNRKLDVKLLYPVSRFQQDQ 110
iSH2_PI3K_IA_R cd12923
Inter-Src homology 2 (iSH2) helical domain of Class IA Phosphoinositide 3-kinase Regulatory ...
440-599 8.62e-68

Inter-Src homology 2 (iSH2) helical domain of Class IA Phosphoinositide 3-kinase Regulatory subunits; PI3Ks catalyze the transfer of the gamma-phosphoryl group from ATP to the 3-hydroxyl of the inositol ring of D-myo-phosphatidylinositol (PtdIns) or its derivatives. They play an important role in a variety of fundamental cellular processes, including cell motility, the Ras pathway, vesicle trafficking and secretion, immune cell activation, and apoptosis. They are classified according to their substrate specificity, regulation, and domain structure. Class IA PI3Ks are heterodimers of a p110 catalytic (C) subunit and a p85-related regulatory (R) subunit. The R subunit down-regulates PI3K basal activity, stabilizes the C subunit, and plays a role in the activation downstream of tyrosine kinases. All R subunits contain two SH2 domains that flank an intervening helical domain (iSH2), which binds to the N-terminal adaptor-binding domain (ABD) of the catalytic subunit. In vertebrates, there are three genes (PIK3R1, PIK3R2, and PIK3R3) that encode for different Class IA PI3K R subunits.


Pssm-ID: 214016 [Multi-domain]  Cd Length: 152  Bit Score: 219.79  E-value: 8.62e-68
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 32455248 440 DNIEAVGKKLHEYNTQFQEKSREYDRLYEEYTRTSQEIQMKRTAIEAFNETIKIFEEQCQTQERYSKEYiekfkregNEK 519
Cdd:cd12923   1 DDVEKLAKKLKEINKEYLDKSREYDELYEKYNKLSQEIQLKRQALEAFEEAVKMFEEQLRTQEKFQKEA--------QPH 72
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 32455248 520 EIQRIMHNYDKLKSRISEIIDSRRRLEEDLKKQAAEYREIDKRMNSIKPDLIQLRKTRDQYLMWLTQKGVRQKKLNEWLG 599
Cdd:cd12923  73 EKQRLMENNELLKSRLKELEESKEQLEEDLRKQVAYNRELEREMNSLKPELMQLRKQKDQYLRWLKRKGVSQEEINQLLK 152
SH3_PI3K_p85alpha cd11910
Src Homology 3 domain of the p85alpha regulatory subunit of Class IA Phosphatidylinositol ...
5-79 4.67e-49

Src Homology 3 domain of the p85alpha regulatory subunit of Class IA Phosphatidylinositol 3-kinases; Class I PI3Ks convert PtdIns(4,5)P2 to the critical second messenger PtdIns(3,4,5)P3. They are heterodimers and exist in multiple isoforms consisting of one catalytic subunit (out of four isoforms) and one of several regulatory subunits. Class IA PI3Ks associate with the p85 regulatory subunit family, which contains SH3, RhoGAP, and SH2 domains. The p85 subunits recruit the PI3K p110 catalytic subunit to the membrane, where p110 phosphorylates inositol lipids. Vertebrates harbor two p85 isoforms, called alpha and beta. In addition to regulating the p110 subunit, p85alpha interacts with activated FGFR3. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 212843  Cd Length: 75  Bit Score: 166.23  E-value: 4.67e-49
                        10        20        30        40        50        60        70
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 32455248   5 GYQYRALYDYKKEREEDIDLHLGDILTVNKGSLVALGFSDGQEARPEEIGWLNGYNETTGERGDFPGTYVEYIGR 79
Cdd:cd11910   1 GYQYRALYDYKKEREEDIDLHLGDILTVNKGSLLALGFSEGQEARPEEIGWLNGYNETTGERGDFPGTYVEYIGR 75
RhoGAP smart00324
GTPase-activator protein for Rho-like GTPases; GTPase activator proteins towards Rho/Rac ...
129-295 1.77e-41

GTPase-activator protein for Rho-like GTPases; GTPase activator proteins towards Rho/Rac/Cdc42-like small GTPases. etter domain limits and outliers.


Pssm-ID: 214618  Cd Length: 174  Bit Score: 148.95  E-value: 1.77e-41
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 32455248    129 PPLLIKLVEAIEKKGLECSTLYRTQ-SSSNLAELRQLLDCDT-PSVDLEMIDVHVLADAFKRYLLDLPNPVIPAAVYSEM 206
Cdd:smart00324   4 PIIVEKCIEYLEKRGLDTEGIYRVSgSKSRVKELRDAFDSGPdPDLDLSEYDVHDVAGLLKLFLRELPEPLITYELYEEF 83
                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 32455248    207 ISLApEVQSSEEYIQLLKKLIRSpsIPHQYWLTLQYLLKHFFKLSQTSSKNLLNARVLSEIFSPMLFRFSA---ASSDNT 283
Cdd:smart00324  84 IEAA-KLEDETERLRALRELLSL--LPPANRATLRYLLAHLNRVAEHSEENKMTARNLAIVFGPTLLRPPDgevASLKDI 160
                          170
                   ....*....|..
gi 32455248    284 ENLIKVIEILIS 295
Cdd:smart00324 161 RHQNTVIEFLIE 172
SH3_PI3K_p85 cd11776
Src Homology 3 domain of the p85 regulatory subunit of Class IA Phosphatidylinositol 3-kinases; ...
6-77 1.68e-39

Src Homology 3 domain of the p85 regulatory subunit of Class IA Phosphatidylinositol 3-kinases; Class I PI3Ks convert PtdIns(4,5)P2 to the critical second messenger PtdIns(3,4,5)P3. They are heterodimers and exist in multiple isoforms consisting of one catalytic subunit (out of four isoforms) and one of several regulatory subunits. Class IA PI3Ks associate with the p85 regulatory subunit family, which contains SH3, RhoGAP, and SH2 domains. The p85 subunits recruit the PI3K p110 catalytic subunit to the membrane, where p110 phosphorylates inositol lipids. Vertebrates harbor two p85 isoforms, called alpha and beta. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 212710  Cd Length: 72  Bit Score: 139.57  E-value: 1.68e-39
                        10        20        30        40        50        60        70
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|..
gi 32455248   6 YQYRALYDYKKEREEDIDLHLGDILTVNKGSLVALGFSDGQEARPEEIGWLNGYNETTGERGDFPGTYVEYI 77
Cdd:cd11776   1 VQYRALYDYEKERDEDIILKTGDVLVVENPELLALGVPDGKETVPKPEGWLEGKNERTGERGDFPGTYVEFY 72
RhoGAP cd00159
RhoGAP: GTPase-activator protein (GAP) for Rho-like GTPases; GAPs towards Rho/Rac/Cdc42-like ...
129-295 7.02e-38

RhoGAP: GTPase-activator protein (GAP) for Rho-like GTPases; GAPs towards Rho/Rac/Cdc42-like small GTPases. Small GTPases (G proteins) cluster into distinct families, and all act as molecular switches, active in their GTP-bound form but inactive when bound to GDP. The Rho family of small G proteins, which includes Cdc42Hs, activates effectors involved in a wide variety of developmental processes, including regulation of cytoskeleton formation, cell proliferation and the JNK signaling pathway. G proteins generally have a low intrinsic GTPase hydrolytic activity but there are family-specific groups of GAPs that enhance the rate of GTP hydrolysis by several orders of magnitude. The RhoGAPs are one of the major classes of regulators of Rho G proteins.


Pssm-ID: 238090 [Multi-domain]  Cd Length: 169  Bit Score: 138.59  E-value: 7.02e-38
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 32455248 129 PPLLIKLVEAIEKKGLECSTLYRTQ-SSSNLAELRQLLDCDTPSVDLEMIDVHVLADAFKRYLLDLPNPVIPAAVYSEMI 207
Cdd:cd00159   1 PLIIEKCIEYLEKNGLNTEGIFRVSgSASKIEELKKKFDRGEDIDDLEDYDVHDVASLLKLYLRELPEPLIPFELYDEFI 80
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 32455248 208 SLApEVQSSEEYIQLLKKLIRspSIPHQYWLTLQYLLKHFFKLSQTSSKNLLNARVLSEIFSPMLFR---FSAASSDNTE 284
Cdd:cd00159  81 ELA-KIEDEEERIEALKELLK--SLPPENRDLLKYLLKLLHKISQNSEVNKMTASNLAIVFAPTLLRppdSDDELLEDIK 157
                       170
                ....*....|.
gi 32455248 285 NLIKVIEILIS 295
Cdd:cd00159 158 KLNEIVEFLIE 168
RhoGAP pfam00620
RhoGAP domain; GTPase activator proteins towards Rho/Rac/Cdc42-like small GTPases.
129-274 1.28e-35

RhoGAP domain; GTPase activator proteins towards Rho/Rac/Cdc42-like small GTPases.


Pssm-ID: 459875  Cd Length: 148  Bit Score: 131.51  E-value: 1.28e-35
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 32455248   129 PPLLIKLVEAIEKKGLECSTLYRTQ-SSSNLAELRQLLDCD-TPSVDLEMIDVHVLADAFKRYLLDLPNPVIPAAVYSEM 206
Cdd:pfam00620   1 PLIVRKCVEYLEKRGLDTEGIFRVSgSASRIKELREAFDRGpDVDLDLEEEDVHVVASLLKLFLRELPEPLLTFELYEEF 80
                          90       100       110       120       130       140
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 32455248   207 ISLApEVQSSEEYIQLLKKLIRspSIPHQYWLTLQYLLKHFFKLSQTSSKNLLNARVLSEIFSPMLFR 274
Cdd:pfam00620  81 IEAA-KLPDEEERLEALRELLR--KLPPANRDTLRYLLAHLNRVAQNSDVNKMNAHNLAIVFGPTLLR 145
SH3_PI3K_p85beta cd11909
Src Homology 3 domain of the p85beta regulatory subunit of Class IA Phosphatidylinositol ...
6-78 1.17e-31

Src Homology 3 domain of the p85beta regulatory subunit of Class IA Phosphatidylinositol 3-kinases; Class I PI3Ks convert PtdIns(4,5)P2 to the critical second messenger PtdIns(3,4,5)P3. They are heterodimers and exist in multiple isoforms consisting of one catalytic subunit (out of four isoforms) and one of several regulatory subunits. Class IA PI3Ks associate with the p85 regulatory subunit family, which contains SH3, RhoGAP, and SH2 domains. The p85 subunits recruit the PI3K p110 catalytic subunit to the membrane, where p110 phosphorylates inositol lipids. Vertebrates harbor two p85 isoforms, called alpha and beta. In addition to regulating the p110 subunit, p85beta binds CD28 and may be involved in the activation and differentiation of antigen-stimulated 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: 212842  Cd Length: 74  Bit Score: 117.63  E-value: 1.17e-31
                        10        20        30        40        50        60        70
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|...
gi 32455248   6 YQYRALYDYKKEREEDIDLHLGDILTVNKGSLVALGFSDGQEARPEEIGWLNGYNETTGERGDFPGTYVEYIG 78
Cdd:cd11909   1 FQYRALYPYRKEREEDIDLLPGDVLTVSRAALQALGVKEGGEQCPQSIGWILGLNERTKQRGDFPGTYVEFLG 73
SH2 smart00252
Src homology 2 domains; Src homology 2 domains bind phosphotyrosine-containing polypeptides ...
332-413 1.93e-24

Src homology 2 domains; Src homology 2 domains bind phosphotyrosine-containing polypeptides via 2 surface pockets. Specificity is provided via interaction with residues that are distinct from the phosphotyrosine. Only a single occurrence of a SH2 domain has been found in S. cerevisiae.


Pssm-ID: 214585 [Multi-domain]  Cd Length: 84  Bit Score: 97.30  E-value: 1.93e-24
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 32455248    332 EWYWGDISREEVNEKLRDTADGTFLVRDaSTKMHGDYTLTLRKGGNNKLIKIFH-RDGKYGFSDPLTFSSVVELINHYRN 410
Cdd:smart00252   2 PWYHGFISREEAEKLLKNEGDGDFLVRD-SESSPGDYVLSVRVKGKVKHYRIRRnEDGKFYLEGGRKFPSLVELVEHYQK 80

                   ...
gi 32455248    411 ESL 413
Cdd:smart00252  81 NSL 83
SH2 pfam00017
SH2 domain;
624-698 1.54e-22

SH2 domain;


Pssm-ID: 425423 [Multi-domain]  Cd Length: 77  Bit Score: 91.89  E-value: 1.54e-22
                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 32455248   624 WNVGSSNRNKAENLLR-GKRDGTFLVRES-SKQGCYACSVVVDGEVKHCVINKTATG--YGFAEPYnlYSSLKELVLHY 698
Cdd:pfam00017   1 WYHGKISRQEAERLLLnGKPDGTFLVRESeSTPGGYTLSVRDDGKVKHYKIQSTDNGgyYISGGVK--FSSLAELVEHY 77
SH2 smart00252
Src homology 2 domains; Src homology 2 domains bind phosphotyrosine-containing polypeptides ...
624-704 9.41e-21

Src homology 2 domains; Src homology 2 domains bind phosphotyrosine-containing polypeptides via 2 surface pockets. Specificity is provided via interaction with residues that are distinct from the phosphotyrosine. Only a single occurrence of a SH2 domain has been found in S. cerevisiae.


Pssm-ID: 214585 [Multi-domain]  Cd Length: 84  Bit Score: 86.90  E-value: 9.41e-21
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 32455248    624 WNVGSSNRNKAENLLRGKRDGTFLVRES-SKQGCYACSVVVDGEVKHCVINKTATGYGFAEPYNLYSSLKELVLHYQHTS 702
Cdd:smart00252   3 WYHGFISREEAEKLLKNEGDGDFLVRDSeSSPGDYVLSVRVKGKVKHYRIRRNEDGKFYLEGGRKFPSLVELVEHYQKNS 82

                   ..
gi 32455248    703 LV 704
Cdd:smart00252  83 LG 84
SH2 pfam00017
SH2 domain;
333-408 1.08e-19

SH2 domain;


Pssm-ID: 425423 [Multi-domain]  Cd Length: 77  Bit Score: 83.80  E-value: 1.08e-19
                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 32455248   333 WYWGDISREEVNEKLRDT-ADGTFLVRDASTKMhGDYTLTLRKGGNNKLIKI-FHRDGKYGFSDPLTFSSVVELINHY 408
Cdd:pfam00017   1 WYHGKISRQEAERLLLNGkPDGTFLVRESESTP-GGYTLSVRDDGKVKHYKIqSTDNGGYYISGGVKFSSLAELVEHY 77
RhoGAP_myosin_IX cd04377
RhoGAP_myosin_IX: RhoGAP (GTPase-activator protein [GAP] for Rho-like small GTPases) domain ...
129-274 4.08e-19

RhoGAP_myosin_IX: RhoGAP (GTPase-activator protein [GAP] for Rho-like small GTPases) domain present in class IX myosins. Class IX myosins contain a characteristic head domain, a neck domain, a tail domain which contains a C6H2-zinc binding motif and a RhoGAP domain. Class IX myosins are single-headed, processive myosins that are partly cytoplasmic, and partly associated with membranes and the actin cytoskeleton. Class IX myosins are implicated in the regulation of neuronal morphogenesis and function of sensory systems, like the inner ear. There are two major isoforms, myosin IXA and IXB with several splice variants, which are both expressed in developing neurons. Small GTPases cluster into distinct families, and all act as molecular switches, active in their GTP-bound form but inactive when GDP-bound. The Rho family of GTPases activates effectors involved in a wide variety of developmental processes, including regulation of cytoskeleton formation, cell proliferation and the JNK signaling pathway. GTPases generally have a low intrinsic GTPase hydrolytic activity but there are family-specific groups of GAPs that enhance the rate of GTP hydrolysis by several orders of magnitude.


Pssm-ID: 239842  Cd Length: 186  Bit Score: 85.57  E-value: 4.08e-19
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 32455248 129 PPLLIKLVEAIEKKGLECSTLYRTQSSSN-LAELRQLLDCDTPSVDLEMIDVHVLADAFKRYLLDLPNPVIPAAVYSEMI 207
Cdd:cd04377  16 PLVLEKLLEHIEMHGLYTEGIYRKSGSANkIKELRQGLDTDPDSVNLEDYPIHVITSVLKQWLRELPEPLMTFELYENFL 95
                        90       100       110       120       130       140
                ....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 32455248 208 SlAPEVQSSEEYIQLLKKLIRSPSIPHQYwlTLQYLLKHFFKLSQTSSKNLLNARVLSEIFSPMLFR 274
Cdd:cd04377  96 R-AMELEEKQERVRALYSVLEQLPRANLN--TLERLIFHLVRVALQEEVNRMSANALAIVFAPCILR 159
SH2 cd00173
Src homology 2 (SH2) domain; In general, SH2 domains are involved in signal transduction; they ...
332-408 8.90e-19

Src homology 2 (SH2) domain; In general, SH2 domains are involved in signal transduction; they bind pTyr-containing polypeptide ligands via two surface pockets, a pTyr and hydrophobic binding pocket, allowing proteins with SH2 domains to localize to tyrosine phosphorylated sites. They are present in a wide array of proteins including: adaptor proteins (Nck1, Crk, Grb2), scaffolds (Slp76, Shc, Dapp1), kinases (Src, Syk, Fps, Tec), phosphatases (Shp-1, Shp-2), transcription factors (STAT1), Ras signaling molecules (Ras-Gap), ubiquitination factors (c-Cbl), cytoskeleton regulators (Tensin), signal regulators (SAP), and phospholipid second messengers (PLCgamma), amongst others.


Pssm-ID: 198173 [Multi-domain]  Cd Length: 79  Bit Score: 81.35  E-value: 8.90e-19
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 32455248 332 EWYWGDISREEVNEKLRDTADGTFLVRDaSTKMHGDYTLTLRKGGNN-KLIKIFHRDGKYGF--SDPLTFSSVVELINHY 408
Cdd:cd00173   1 PWFHGSISREEAERLLRGKPDGTFLVRE-SSSEPGDYVLSVRSGDGKvKHYLIERNEGGYYLlgGSGRTFPSLPELVEHY 79
SH2 cd00173
Src homology 2 (SH2) domain; In general, SH2 domains are involved in signal transduction; they ...
624-698 1.14e-18

Src homology 2 (SH2) domain; In general, SH2 domains are involved in signal transduction; they bind pTyr-containing polypeptide ligands via two surface pockets, a pTyr and hydrophobic binding pocket, allowing proteins with SH2 domains to localize to tyrosine phosphorylated sites. They are present in a wide array of proteins including: adaptor proteins (Nck1, Crk, Grb2), scaffolds (Slp76, Shc, Dapp1), kinases (Src, Syk, Fps, Tec), phosphatases (Shp-1, Shp-2), transcription factors (STAT1), Ras signaling molecules (Ras-Gap), ubiquitination factors (c-Cbl), cytoskeleton regulators (Tensin), signal regulators (SAP), and phospholipid second messengers (PLCgamma), amongst others.


Pssm-ID: 198173 [Multi-domain]  Cd Length: 79  Bit Score: 80.96  E-value: 1.14e-18
                        10        20        30        40        50        60        70
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 32455248 624 WNVGSSNRNKAENLLRGKRDGTFLVRESSKQ-GCYACSVVVD-GEVKHCVINKTATGYGFAEPYNL-YSSLKELVLHY 698
Cdd:cd00173   2 WFHGSISREEAERLLRGKPDGTFLVRESSSEpGDYVLSVRSGdGKVKHYLIERNEGGYYLLGGSGRtFPSLPELVEHY 79
RhoGAP_ARAP cd04385
RhoGAP_ARAP: RhoGAP (GTPase-activator protein [GAP] for Rho-like small GTPases) domain present ...
106-294 2.29e-18

RhoGAP_ARAP: RhoGAP (GTPase-activator protein [GAP] for Rho-like small GTPases) domain present in ARAPs. ARAPs (also known as centaurin deltas) contain, besides the RhoGAP domain, an Arf GAP, ankyrin repeat ras-associating, and PH domains. Since their ArfGAP activity is PIP3-dependent, ARAPs are considered integration points for phosphoinositide, Arf and Rho signaling. Small GTPases cluster into distinct families, and all act as molecular switches, active in their GTP-bound form but inactive when GDP-bound. The Rho family of GTPases activates effectors involved in a wide variety of developmental processes, including regulation of cytoskeleton formation, cell proliferation and the JNK signaling pathway. GTPases generally have a low intrinsic GTPase hydrolytic activity but there are family-specific groups of GAPs that enhance the rate of GTP hydrolysis by several orders of magnitude.


Pssm-ID: 239850  Cd Length: 184  Bit Score: 83.51  E-value: 2.29e-18
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 32455248 106 ADVEQQALTlpdlaeqfappDIAPPLLI-KLVEAIEKKGLECSTLYR---TQSSSN--LAELRQlldcDTPSVDLEMID- 178
Cdd:cd04385   3 PALEDQQLT-----------DNDIPVIVdKCIDFITQHGLMSEGIYRkngKNSSVKklLEAFRK----DARSVQLREGEy 67
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 32455248 179 -VHVLADAFKRYLLDLPNPVIPAAVYSEMISLApEVQSSEEYIQLLKKLIRS-PSIPHQywlTLQYLLKHFFKLSQTSSK 256
Cdd:cd04385  68 tVHDVADVLKRFLRDLPDPLLTSELHAEWIEAA-ELENKDERIARYKELIRRlPPINRA---TLKVLIGHLYRVQKHSDE 143
                       170       180       190
                ....*....|....*....|....*....|....*...
gi 32455248 257 NLLNARVLSEIFSPMLFRFSAASSDNTENLIKVIEILI 294
Cdd:cd04385 144 NQMSVHNLALVFGPTLFQTDEHSVGQTSHEVKVIEDLI 181
RhoGAP_fRGD1 cd04398
RhoGAP_fRGD1: RhoGAP (GTPase-activator protein [GAP] for Rho-like small GTPases) domain of ...
126-294 2.44e-18

RhoGAP_fRGD1: RhoGAP (GTPase-activator protein [GAP] for Rho-like small GTPases) domain of fungal RGD1-like proteins. Yeast Rgd1 is a GAP protein for Rho3 and Rho4 and plays a role in low-pH response. Small GTPases cluster into distinct families, and all act as molecular switches, active in their GTP-bound form but inactive when GDP-bound. The Rho family of GTPases activates effectors involved in a wide variety of developmental processes, including regulation of cytoskeleton formation, cell proliferation and the JNK signaling pathway. GTPases generally have a low intrinsic GTPase hydrolytic activity but there are family-specific groups of GAPs that enhance the rate of GTP hydrolysis by several orders of magnitude.


Pssm-ID: 239863  Cd Length: 192  Bit Score: 83.61  E-value: 2.44e-18
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 32455248 126 DIAPPLLIKLVEAIEKKGLECSTLYRTQSS-SNLAELRQLLDCDTPSVDLEM-----IDVHVLADAFKRYLLDLPNPVIP 199
Cdd:cd04398  14 DNVPNIVYQCIQAIENFGLNLEGIYRLSGNvSRVNKLKELFDKDPLNVLLISpedyeSDIHSVASLLKLFFRELPEPLLT 93
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 32455248 200 AAVYSEMIslapEVQSSEEYIQLLKKLIRS-PSIPH-QYWlTLQYLLKHFFKLSQTSSKNLLNARVLSEIFSPMLFRfsa 277
Cdd:cd04398  94 KALSREFI----EAAKIEDESRRRDALHGLiNDLPDaNYA-TLRALMFHLARIKEHESVNRMSVNNLAIIWGPTLMN--- 165
                       170       180
                ....*....|....*....|
gi 32455248 278 ASSDNTENL---IKVIEILI 294
Cdd:cd04398 166 AAPDNAADMsfqSRVIETLL 185
SH2_Vav_family cd09940
Src homology 2 (SH2) domain found in the Vav family; Vav proteins are involved in several ...
621-718 3.22e-18

Src homology 2 (SH2) domain found in the Vav family; Vav proteins are involved in several processes that require cytoskeletal reorganization, such as the formation of the immunological synapse (IS), phagocytosis, platelet aggregation, spreading, and transformation. Vavs function as guanine nucleotide exchange factors (GEFs) for the Rho/Rac family of GTPases. Vav family members have several conserved motifs/domains including: a leucine-rich region, a leucine-zipper, a calponin homology (CH) domain, an acidic domain, a Dbl-homology (DH) domain, a pleckstrin homology (PH) domain, a cysteine-rich domain, 2 SH3 domains, a proline-rich region, and a SH2 domain. Vavs are the only known Rho GEFs that have both the DH/PH motifs and SH2/SH3 domains in the same protein. The leucine-rich helix-loop-helix (HLH) domain is thought to be involved in protein heterodimerization with other HLH proteins and it may function as a negative regulator by forming inactive heterodimers. The CH domain is usually involved in the association with filamentous actin, but in Vav it controls NFAT stimulation, Ca2+ mobilization, and its transforming activity. Acidic domains are involved in protein-protein interactions and contain regulatory tyrosines. The DH domain is a GDP-GTP exchange factor on Rho/Rac GTPases. The PH domain in involved in interactions with GTP-binding proteins, lipids and/or phosphorylated serine/threonine residues. The SH3 domain is involved in localization of proteins to specific sites within the cell interacting with protein with proline-rich sequences. The SH2 domain mediates a high affinity interaction with tyrosine phosphorylated proteins. There are three Vav mammalian family members: Vav1 which is expressed in the hematopoietic system, Vav2 and Vav3 are more ubiquitously expressed. The members here include insect and amphibian Vavs. In general SH2 domains are involved in signal transduction. They typically bind pTyr-containing ligands via two surface pockets, a pTyr and hydrophobic binding pocket, allowing proteins with SH2 domains to localize to tyrosine phosphorylated sites.


Pssm-ID: 198193  Cd Length: 102  Bit Score: 80.42  E-value: 3.22e-18
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 32455248 621 EKTWNVGSSNRNKAENLLRGKRDGTFLVRESSKQ-GCYACSVVVDGEVKHCVINKTATG-YGFAEPYnLYSSLKELVLHY 698
Cdd:cd09940   4 EFLWFVGEMERDTAENRLENRPDGTYLVRVRPQGeTQYALSIKYNGDVKHMKIEQRSDGlYYLSESR-HFKSLVELVNYY 82
                        90       100
                ....*....|....*....|
gi 32455248 699 QHTSLVQHNDSLNVTLAYPV 718
Cdd:cd09940  83 ERNSLGENFAGLDTTLKWPY 102
RhoGAP_ARHGAP27_15_12_9 cd04403
RhoGAP_ARHGAP27_15_12_9: GTPase-activator protein (GAP) domain for Rho-like GTPases found in ...
130-274 5.14e-18

RhoGAP_ARHGAP27_15_12_9: GTPase-activator protein (GAP) domain for Rho-like GTPases found in ARHGAP27 (also called CAMGAP1), ARHGAP15, 12 and 9-like proteins; This subgroup of ARHGAPs are multidomain proteins that contain RhoGAP, PH, SH3 and WW domains. Most members that are studied show GAP activity towards Rac1, some additionally show activity towards Cdc42. Small GTPases cluster into distinct families, and all act as molecular switches, active in their GTP-bound form but inactive when GDP-bound. The Rho family of GTPases activates effectors involved in a wide variety of developmental processes, including regulation of cytoskeleton formation, cell proliferation and the JNK signaling pathway. GTPases generally have a low intrinsic GTPase hydrolytic activity but there are family-specific groups of GAPs that enhance the rate of GTP hydrolysis by several orders of magnitude.


Pssm-ID: 239868 [Multi-domain]  Cd Length: 187  Bit Score: 82.44  E-value: 5.14e-18
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 32455248 130 PLLIKL-VEAIEKKGLECSTLYRTqsSSNLA---ELRQLLDCDTpSVDLEMI---DVHVLADAFKRYLLDLPNPVIPAAV 202
Cdd:cd04403  17 PKFVRLcIEAVEKRGLDVDGIYRV--SGNLAviqKLRFAVDHDE-KLDLDDSkweDIHVITGALKLFFRELPEPLFPYSL 93
                        90       100       110       120       130       140       150
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|..
gi 32455248 203 YSEMISlAPEVQSSEEYIQLLKKLIRSPSIPHQYwlTLQYLLKHFFKLSQTSSKNLLNARVLSEIFSPMLFR 274
Cdd:cd04403  94 FNDFVA-AIKLSDYEQRVSAVKDLIKSLPKPNHD--TLKMLFRHLCRVIEHGEKNRMTTQNLAIVFGPTLLR 162
RhoGAP_p190 cd04373
RhoGAP_p190: RhoGAP (GTPase-activator protein [GAP] for Rho-like small GTPases) domain of ...
118-294 3.77e-17

RhoGAP_p190: RhoGAP (GTPase-activator protein [GAP] for Rho-like small GTPases) domain of p190-like proteins. p190, also named RhoGAP5, plays a role in neuritogenesis and axon branch stability. p190 shows a preference for Rho, over Rac and Cdc42, and consists of an N-terminal GTPase domain and a C-terminal GAP domain. The central portion of p190 contains important regulatory phosphorylation sites. Small GTPases cluster into distinct families, and all act as molecular switches, active in their GTP-bound form but inactive when GDP-bound. The Rho family of GTPases activates effectors involved in a wide variety of developmental processes, including regulation of cytoskeleton formation, cell proliferation and the JNK signaling pathway. GTPases generally have a low intrinsic GTPase hydrolytic activity but there are family-specific groups of GAPs that enhance the rate of GTP hydrolysis by several orders of magnitude.


Pssm-ID: 239838  Cd Length: 185  Bit Score: 80.19  E-value: 3.77e-17
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 32455248 118 LAEQFAPPDIAPPLLIKLVEAIEKKGLECSTLYRTQSS-SNLAELRQLLDCDTpSVDLEMID--VHVLADAFKRYLLDLP 194
Cdd:cd04373   5 LANVVTSEKPIPIFLEKCVEFIEATGLETEGIYRVSGNkTHLDSLQKQFDQDH-NLDLVSKDftVNAVAGALKSFFSELP 83
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 32455248 195 NPVIPAAVYSEMISLApEVQSSEEYIQLLKKLIRSpsIPHQYWLTLQYLLKHFFKLSQTSSKNLLNARVLSEIFSPMLFR 274
Cdd:cd04373  84 DPLIPYSMHLELVEAA-KINDREQRLHALKELLKK--FPPENFDVFKYVITHLNKVSQNSKVNLMTSENLSICFWPTLMR 160
                       170       180
                ....*....|....*....|...
gi 32455248 275 FSAASSDNTENLI---KVIEILI 294
Cdd:cd04373 161 PDFTSMEALSATRiyqTIIETFI 183
RhoGAP_GMIP_PARG1 cd04378
RhoGAP_GMIP_PARG1: RhoGAP (GTPase-activator protein [GAP] for Rho-like small GTPases) domain ...
125-295 4.76e-17

RhoGAP_GMIP_PARG1: RhoGAP (GTPase-activator protein [GAP] for Rho-like small GTPases) domain of GMIP (Gem interacting protein) and PARG1 (PTPL1-associated RhoGAP1). GMIP plays important roles in neurite growth and axonal guidance, and interacts with Gem, a member of the RGK subfamily of the Ras small GTPase superfamily, through the N-terminal half of the protein. GMIP contains a C-terminal RhoGAP domain. GMIP inhibits RhoA function, but is inactive towards Rac1 and Cdc41. PARG1 interacts with Rap2, also a member of the Ras small GTPase superfamily whose exact function is unknown, and shows strong preference for Rho. Small GTPases cluster into distinct families, and all act as molecular switches, active in their GTP-bound form but inactive when GDP-bound. The Rho family of GTPases activates effectors involved in a wide variety of developmental processes, including regulation of cytoskeleton formation, cell proliferation and the JNK signaling pathway. GTPases generally have a low intrinsic GTPase hydrolytic activity but there are family-specific groups of GAPs that enhance the rate of GTP hydrolysis by several orders of magnitude.


Pssm-ID: 239843  Cd Length: 203  Bit Score: 80.16  E-value: 4.76e-17
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 32455248 125 PDIAPPLLIKLVEAIEKKGLECSTLYRTQSSSNLAE-LRQLLDCDTPSVDLEMIDVHVLADAFKRYLLDLPNPVIPAAVY 203
Cdd:cd04378  13 PDEVPFIIKKCTSEIENRALGVQGIYRVSGSKARVEkLCQAFENGKDLVELSELSPHDISSVLKLFLRQLPEPLILFRLY 92
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 32455248 204 SEMISLAPEVQS-------------SEEYIQLLKKLIRspSIPHQYWLTLQYLLKHFFKLSQTSSKNLLNARVLSEIFSP 270
Cdd:cd04378  93 NDFIALAKEIQRdteedkapntpieVNRIIRKLKDLLR--QLPASNYNTLQHLIAHLYRVAEQFEENKMSPNNLGIVFGP 170
                       170       180       190
                ....*....|....*....|....*....|..
gi 32455248 271 MLFRFSAASSD-------NTENLIKVIEILIS 295
Cdd:cd04378 171 TLIRPRPGDADvslsslvDYGYQARLVEFLIT 202
RhoGAP_chimaerin cd04372
RhoGAP_chimaerin: RhoGAP (GTPase-activator protein [GAP] for Rho-like small GTPases) domain of ...
129-297 6.19e-17

RhoGAP_chimaerin: RhoGAP (GTPase-activator protein [GAP] for Rho-like small GTPases) domain of chimaerins. Chimaerins are a family of phorbolester- and diacylglycerol-responsive GAPs specific for the Rho-like GTPase Rac. Chimaerins exist in two alternative splice forms that each contain a C-terminal GAP domain, and a central C1 domain which binds phorbol esters, inducing a conformational change that activates the protein; one splice form is lacking the N-terminal Src homology-2 (SH2) domain. Small GTPases cluster into distinct families, and all act as molecular switches, active in their GTP-bound form but inactive when GDP-bound. The Rho family of GTPases activates effectors involved in a wide variety of developmental processes, including regulation of cytoskeleton formation, cell proliferation and the JNK signaling pathway. GTPases generally have a low intrinsic GTPase hydrolytic activity but there are family-specific groups of GAPs that enhance the rate of GTP hydrolysis by several orders of magnitude.


Pssm-ID: 239837 [Multi-domain]  Cd Length: 194  Bit Score: 79.48  E-value: 6.19e-17
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 32455248 129 PPLLIKLVEAIEKKGLECSTLYRTQSSSNLAE-LRQLLDCDTPSVDLEMI---DVHVLADAFKRYLLDLPNPVIPAAVYS 204
Cdd:cd04372  17 PMVVDMCIREIEARGLQSEGLYRVSGFAEEIEdVKMAFDRDGEKADISATvypDINVITGALKLYFRDLPIPVITYDTYP 96
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 32455248 205 EMISlAPEVQSSEEYIQLLKKLIRSpsIPHQYWLTLQYLLKHFFKLSQTSSKNLLNARVLSEIFSPMLFRFSAASSDNTE 284
Cdd:cd04372  97 KFID-AAKISNPDERLEAVHEALML--LPPAHYETLRYLMEHLKRVTLHEKDNKMNAENLGIVFGPTLMRPPEDSALTTL 173
                       170
                ....*....|....*..
gi 32455248 285 N----LIKVIEILISTE 297
Cdd:cd04372 174 NdmryQILIVQLLITNE 190
RhoGAP_myosin_IXA cd04406
RhoGAP_myosin_IXA: RhoGAP (GTPase-activator protein [GAP] for Rho-like small GTPases) domain ...
126-296 6.52e-17

RhoGAP_myosin_IXA: RhoGAP (GTPase-activator protein [GAP] for Rho-like small GTPases) domain present in myosins IXA. Class IX myosins contain a characteristic head domain, a neck domain and a tail domain which contains a C6H2-zinc binding motif and a Rho-GAP domain. Class IX myosins are single-headed, processive myosins that are partly cytoplasmic, and partly associated with membranes and the actin cytoskeleton. Class IX myosins are implicated in the regulation of neuronal morphogenesis and function of sensory systems, like the inner ear. There are two major isoforms, myosin IXA and IXB with several splice variants, which are both expressed in developing neurons. Small GTPases cluster into distinct families, and all act as molecular switches, active in their GTP-bound form but inactive when GDP-bound. The Rho family of GTPases activates effectors involved in a wide variety of developmental processes, including regulation of cytoskeleton formation, cell proliferation and the JNK signaling pathway. GTPases generally have a low intrinsic GTPase hydrolytic activity but there are family-specific groups of GAPs that enhance the rate of GTP hydrolysis by several orders of magnitude.


Pssm-ID: 239871  Cd Length: 186  Bit Score: 79.27  E-value: 6.52e-17
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 32455248 126 DIAPPLLI-KLVEAIEKKGLECSTLYRTQSSSN-LAELRQLLDCDTPSVDLEMIDVHVLADAFKRYLLDLPNPVIPAAVY 203
Cdd:cd04406  12 DRSVPLVVeKLINYIEMHGLYTEGIYRKSGSTNkIKELRQGLDTDANSVNLDDYNIHVIASVFKQWLRDLPNPLMTFELY 91
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 32455248 204 SEMISlAPEVQSSEEYIQLLKKLIRSPSIPHQYwlTLQYLLKHFFKLSQTSSKNLLNARVLSEIFSPMLFRfsaaSSDNT 283
Cdd:cd04406  92 EEFLR-AMGLQERRETVRGVYSVIDQLSRTHLN--TLERLIFHLVRIALQEETNRMSANALAIVFAPCILR----CPDTT 164
                       170
                ....*....|...
gi 32455248 284 ENLIKVIEILIST 296
Cdd:cd04406 165 DPLQSVQDISKTT 177
SH2_cSH2_p85_like cd09930
C-terminal Src homology 2 (cSH2) domain found in p85; Phosphoinositide 3-kinases (PI3Ks) are ...
333-428 1.12e-16

C-terminal Src homology 2 (cSH2) domain found in p85; Phosphoinositide 3-kinases (PI3Ks) are essential for cell growth, migration, and survival. p110, the catalytic subunit, is composed of an adaptor-binding domain, a Ras-binding domain, a C2 domain, a helical domain, and a kinase domain. The regulatory unit is called p85 and is composed of an SH3 domain, a RhoGap domain, a N-terminal SH2 (nSH2) domain, a inter SH2 (iSH2) domain, and C-terminal (cSH2) domain. There are 2 inhibitory interactions between p110alpha and p85 of P13K: 1) p85 nSH2 domain with the C2, helical, and kinase domains of p110alpha and 2) p85 iSH2 domain with C2 domain of p110alpha. There are 3 inhibitory interactions between p110beta and p85 of P13K: 1) p85 nSH2 domain with the C2, helical, and kinase domains of p110beta, 2) p85 iSH2 domain with C2 domain of p110alpha, and 3) p85 cSH2 domain with the kinase domain of p110alpha. It is interesting to note that p110beta is oncogenic as a wild type protein while p110alpha lacks this ability. One explanation is the idea that the regulation of p110beta by p85 is unique because of the addition of inhibitory contacts from the cSH2 domain and the loss of contacts in the iSH2 domain. In general SH2 domains are involved in signal transduction. They typically bind pTyr-containing ligands via two surface pockets, a pTyr and hydrophobic binding pocket, allowing proteins with SH2 domains to localize to tyrosine phosphorylated sites.


Pssm-ID: 198184  Cd Length: 104  Bit Score: 75.91  E-value: 1.12e-16
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 32455248 333 WYWGDISREEVNEKLRDTADGTFLVRDASTKmhGDYTLTLRKGGNNKLIKIFHRDGKYGFSDPLT-FSSVVELINHYRNE 411
Cdd:cd09930   8 WLVGDINRTQAEELLRGKPDGTFLIRESSTQ--GCYACSVVCNGEVKHCVIYKTETGYGFAEPYNlYESLKELVLHYAHN 85
                        90
                ....*....|....*..
gi 32455248 412 SLAQYNPKLDVKLLYPV 428
Cdd:cd09930  86 SLEQHNDSLTVTLAYPV 102
RhoGAP_ARHGAP21 cd04395
RhoGAP_ARHGAP21: RhoGAP (GTPase-activator protein [GAP] for Rho-like small GTPases) domain of ...
124-294 1.28e-16

RhoGAP_ARHGAP21: RhoGAP (GTPase-activator protein [GAP] for Rho-like small GTPases) domain of ArhGAP21-like proteins. ArhGAP21 is a multi-domain protein, containing RhoGAP, PH and PDZ domains, and is believed to play a role in the organization of the cell-cell junction complex. It has been shown to function as a GAP of Cdc42 and RhoA, and to interact with alpha-catenin and Arf6. Small GTPases cluster into distinct families, and all act as molecular switches, active in their GTP-bound form but inactive when GDP-bound. The Rho family of GTPases activates effectors involved in a wide variety of developmental processes, including regulation of cytoskeleton formation, cell proliferation and the JNK signaling pathway. GTPases generally have a low intrinsic GTPase hydrolytic activity but there are family-specific groups of GAPs that enhance the rate of GTP hydrolysis by several orders of magnitude.


Pssm-ID: 239860  Cd Length: 196  Bit Score: 78.60  E-value: 1.28e-16
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 32455248 124 PPDIAPPLLIKLVEA----IEKKGLECSTLYR----TQSSSNLAELRQLLDCDTPSVDLEMIDVHVLADAFKRYLLDLPN 195
Cdd:cd04395  10 PPSSENPYVPLIVEVccniVEARGLETVGIYRvpgnNAAISALQEELNRGGFDIDLQDPRWRDVNVVSSLLKSFFRKLPE 89
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 32455248 196 PVIPAAVYSEMISlAPEVQSSEEYIQLLKKLIRSpsIPHQYWLTLQYLLKHFFKLSQTSSKNLLNARVLSEIFSPMLFRf 275
Cdd:cd04395  90 PLFTNELYPDFIE-ANRIEDPVERLKELRRLIHS--LPDHHYETLKHLIRHLKTVADNSEVNKMEPRNLAIVFGPTLVR- 165
                       170       180
                ....*....|....*....|....*.
gi 32455248 276 saASSDNTENLI-------KVIEILI 294
Cdd:cd04395 166 --TSDDNMETMVthmpdqcKIVETLI 189
SH2_SOCS_family cd09923
Src homology 2 (SH2) domain found in suppressor of cytokine signaling (SOCS) family; SH2 ...
332-408 1.49e-16

Src homology 2 (SH2) domain found in suppressor of cytokine signaling (SOCS) family; SH2 domain found in SOCS proteins. SOCS was first recognized as a group of cytokine-inducible SH2 (CIS) domain proteins comprising eight family members in human (CIS and SOCS1-SOCS7). In addition to the SH2 domain, SOCS proteins have a variable N-terminal domain and a conserved SOCS box in the C-terminal domain. SOCS proteins bind to a substrate via their SH2 domain. The prototypical members, CIS and SOCS1-SOCS3, have been shown to regulate growth hormone signaling in vitro and in a classic negative feedback response compete for binding at phosphotyrosine sites in JAK kinase and receptor pathways to displace effector proteins and target bound receptors for proteasomal degradation. Loss of SOCS activity results in excessive cytokine signaling associated with a variety of hematopoietic, autoimmune, and inflammatory diseases and certain cancers. Members (SOCS4-SOCS7) were identified by their conserved SOCS box, an adapter motif of 3 helices that associates substrate binding domains, such as the SOCS SH2 domain, ankryin, and WD40 with ubiquitin ligase components. These show limited cytokine induction. In general SH2 domains are involved in signal transduction. They typically bind pTyr-containing ligands via two surface pockets, a pTyr and hydrophobic binding pocket, allowing proteins with SH2 domains to localize to tyrosine phosphorylated sites.


Pssm-ID: 198178  Cd Length: 81  Bit Score: 74.93  E-value: 1.49e-16
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 32455248 332 EWYWGDISREEVNEKLRDTADGTFLVRDASTKMHgDYTLTLRKGGNNKLIKIFHRDGKYGF--SDPL--TFSSVVELINH 407
Cdd:cd09923   1 GWYWGGITRYEAEELLAGKPEGTFLVRDSSDSRY-LFSVSFRTYGRTLHARIEYSNGRFSFdsSDPSvpRFPCVVELIEH 79

                .
gi 32455248 408 Y 408
Cdd:cd09923  80 Y 80
SH2_nSH2_p85_like cd09942
N-terminal Src homology 2 (nSH2) domain found in p85; Phosphoinositide 3-kinases (PI3Ks) are ...
621-718 2.04e-16

N-terminal Src homology 2 (nSH2) domain found in p85; Phosphoinositide 3-kinases (PI3Ks) are essential for cell growth, migration, and survival. p110, the catalytic subunit, is composed of an adaptor-binding domain, a Ras-binding domain, a C2 domain, a helical domain, and a kinase domain. The regulatory unit is called p85 and is composed of an SH3 domain, a RhoGap domain, a N-terminal SH2 (nSH2) domain, an internal SH2 (iSH2) domain, and C-terminal (cSH2) domain. There are 2 inhibitory interactions between p110alpha and p85 of P13K: (1) p85 nSH2 domain with the C2, helical, and kinase domains of p110alpha and (2) p85 iSH2 domain with C2 domain of p110alpha. There are 3 inhibitory interactions between p110beta and p85 of P13K: (1) p85 nSH2 domain with the C2, helical, and kinase domains of p110beta, (2) p85 iSH2 domain with C2 domain of p110alpha, and (3) p85 cSH2 domain with the kinase domain of p110alpha. It is interesting to note that p110beta is oncogenic as a wild type protein while p110alpha lacks this ability. One explanation is the idea that the regulation of p110beta by p85 is unique because of the addition of inhibitory contacts from the cSH2 domain and the loss of contacts in the iSH2 domain. In general SH2 domains are involved in signal transduction. They typically bind pTyr-containing ligands via two surface pockets, a pTyr and hydrophobic binding pocket, allowing proteins with SH2 domains to localize to tyrosine phosphorylated sites.


Pssm-ID: 198195  Cd Length: 110  Bit Score: 75.44  E-value: 2.04e-16
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 32455248 621 EKTWNVGSSNRNKAENLLRGKRDGTFLVRE-SSKQGCYACSVVVDGEVKHCVINKTATGYGFAEPYNlYSSLKELVLHYQ 699
Cdd:cd09942   6 EAEWYWGDISREEVNEKMRDTPDGTFLVRDaSTMKGDYTLTLRKGGNNKLIKIFHRDGKYGFSDPLT-FNSVVELINYYR 84
                        90
                ....*....|....*....
gi 32455248 700 HTSLVQHNDSLNVTLAYPV 718
Cdd:cd09942  85 NNSLAEYNRKLDVKLLYPV 103
RhoGAP_myosin_IXB cd04407
RhoGAP_myosin_IXB: RhoGAP (GTPase-activator protein [GAP] for Rho-like small GTPases) domain ...
129-296 2.93e-16

RhoGAP_myosin_IXB: RhoGAP (GTPase-activator protein [GAP] for Rho-like small GTPases) domain present in myosins IXB. Class IX myosins contain a characteristic head domain, a neck domain and a tail domain which contains a C6H2-zinc binding motif and a Rho-GAP domain. Class IX myosins are single-headed, processive myosins that are partly cytoplasmic, and partly associated with membranes and the actin cytoskeleton. Class IX myosins are implicated in the regulation of neuronal morphogenesis and function of sensory systems, like the inner ear. There are two major isoforms, myosin IXA and IXB with several splice variants, which are both expressed in developing neurons Small GTPases cluster into distinct families, and all act as molecular switches, active in their GTP-bound form but inactive when GDP-bound. The Rho family of GTPases activates effectors involved in a wide variety of developmental processes, including regulation of cytoskeleton formation, cell proliferation and the JNK signaling pathway. GTPases generally have a low intrinsic GTPase hydrolytic activity but there are family-specific groups of GAPs that enhance the rate of GTP hydrolysis by several orders of magnitude.


Pssm-ID: 239872 [Multi-domain]  Cd Length: 186  Bit Score: 77.34  E-value: 2.93e-16
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 32455248 129 PPLLIKLVEAIEKKGLECSTLYRTQSSSN-LAELRQLLDCDTPSVDLEMIDVHVLADAFKRYLLDLPNPVIPAAVYSEMI 207
Cdd:cd04407  16 PIVLEKLLEHVEMHGLYTEGIYRKSGSANrMKELHQLLQADPENVKLENYPIHAITGLLKQWLRELPEPLMTFAQYNDFL 95
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 32455248 208 SlAPEVQSSEEYIQLLKKLIRspSIPHQYWLTLQYLLKHFFKLSQTSSKNLLNARVLSEIFSPMLFRfsaaSSDNTENLI 287
Cdd:cd04407  96 R-AVELPEKQEQLQAIYRVLE--QLPTANHNTLERLIFHLVKVALEEDVNRMSPNALAIVFAPCLLR----CPDSSDPLT 168

                ....*....
gi 32455248 288 KVIEILIST 296
Cdd:cd04407 169 SMKDVAKTT 177
SH2_Vav_family cd09940
Src homology 2 (SH2) domain found in the Vav family; Vav proteins are involved in several ...
332-428 6.91e-16

Src homology 2 (SH2) domain found in the Vav family; Vav proteins are involved in several processes that require cytoskeletal reorganization, such as the formation of the immunological synapse (IS), phagocytosis, platelet aggregation, spreading, and transformation. Vavs function as guanine nucleotide exchange factors (GEFs) for the Rho/Rac family of GTPases. Vav family members have several conserved motifs/domains including: a leucine-rich region, a leucine-zipper, a calponin homology (CH) domain, an acidic domain, a Dbl-homology (DH) domain, a pleckstrin homology (PH) domain, a cysteine-rich domain, 2 SH3 domains, a proline-rich region, and a SH2 domain. Vavs are the only known Rho GEFs that have both the DH/PH motifs and SH2/SH3 domains in the same protein. The leucine-rich helix-loop-helix (HLH) domain is thought to be involved in protein heterodimerization with other HLH proteins and it may function as a negative regulator by forming inactive heterodimers. The CH domain is usually involved in the association with filamentous actin, but in Vav it controls NFAT stimulation, Ca2+ mobilization, and its transforming activity. Acidic domains are involved in protein-protein interactions and contain regulatory tyrosines. The DH domain is a GDP-GTP exchange factor on Rho/Rac GTPases. The PH domain in involved in interactions with GTP-binding proteins, lipids and/or phosphorylated serine/threonine residues. The SH3 domain is involved in localization of proteins to specific sites within the cell interacting with protein with proline-rich sequences. The SH2 domain mediates a high affinity interaction with tyrosine phosphorylated proteins. There are three Vav mammalian family members: Vav1 which is expressed in the hematopoietic system, Vav2 and Vav3 are more ubiquitously expressed. The members here include insect and amphibian Vavs. In general SH2 domains are involved in signal transduction. They typically bind pTyr-containing ligands via two surface pockets, a pTyr and hydrophobic binding pocket, allowing proteins with SH2 domains to localize to tyrosine phosphorylated sites.


Pssm-ID: 198193  Cd Length: 102  Bit Score: 73.87  E-value: 6.91e-16
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 32455248 332 EWYWGDISREEVNEKLRDTADGTFLVRdASTKMHGDYTLTLRKGGNNKLIKIFHR-DGKYGFSDPLTFSSVVELINHYRN 410
Cdd:cd09940   6 LWFVGEMERDTAENRLENRPDGTYLVR-VRPQGETQYALSIKYNGDVKHMKIEQRsDGLYYLSESRHFKSLVELVNYYER 84
                        90
                ....*....|....*...
gi 32455248 411 ESLAQYNPKLDVKLLYPV 428
Cdd:cd09940  85 NSLGENFAGLDTTLKWPY 102
RhoGAP_MgcRacGAP cd04382
RhoGAP_MgcRacGAP: RhoGAP (GTPase-activator protein [GAP] for Rho-like small GTPases) domain ...
123-295 7.38e-16

RhoGAP_MgcRacGAP: RhoGAP (GTPase-activator protein [GAP] for Rho-like small GTPases) domain present in MgcRacGAP proteins. MgcRacGAP plays an important dual role in cytokinesis: i) it is part of centralspindlin-complex, together with the mitotic kinesin MKLP1, which is critical for the structure of the central spindle by promoting microtuble bundling. ii) after phosphorylation by aurora B MgcRacGAP becomes an effective regulator of RhoA and plays an important role in the assembly of the contractile ring and the initiation of cytokinesis. MgcRacGAP-like proteins contain a N-terminal C1-like domain, and a C-terminal RhoGAP domain. Small GTPases cluster into distinct families, and all act as molecular switches, active in their GTP-bound form but inactive when GDP-bound. The Rho family of GTPases activates effectors involved in a wide variety of developmental processes, including regulation of cytoskeleton formation, cell proliferation and the JNK signaling pathway. GTPases generally have a low intrinsic GTPase hydrolytic activity but there are family-specific groups of GAPs that enhance the rate of GTP hydrolysis by several orders of magnitude.


Pssm-ID: 239847  Cd Length: 193  Bit Score: 76.56  E-value: 7.38e-16
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 32455248 123 APPDIaPPLLIKLVEAIEKKGLECSTLYRTQSSSNLAE--LRQLLDCDTPSvDLEMIDVHVLADAFKRYLLDLPNPVIPA 200
Cdd:cd04382  13 TSPMI-PALIVHCVNEIEARGLTEEGLYRVSGSEREVKalKEKFLRGKTVP-NLSKVDIHVICGCLKDFLRSLKEPLITF 90
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 32455248 201 AVYSEMIsLAPEVQSSEEYIQLLKKLIRSPSIPHQYwlTLQYLLKHFFKLSQtSSKNLLNARVLSEIFSPMLFRFSAASS 280
Cdd:cd04382  91 ALWKEFM-EAAEILDEDNSRAALYQAISELPQPNRD--TLAFLILHLQRVAQ-SPECKMDINNLARVFGPTIVGYSVPNP 166
                       170       180
                ....*....|....*....|.
gi 32455248 281 D------NTENLIKVIEILIS 295
Cdd:cd04382 167 DpmtilqDTVRQPRVVERLLE 187
SH2_SOCS6 cd10387
Src homology 2 (SH2) domain found in suppressor of cytokine signaling (SOCS) proteins; SH2 ...
333-412 1.16e-14

Src homology 2 (SH2) domain found in suppressor of cytokine signaling (SOCS) proteins; SH2 domain found in SOCS proteins. SOCS was first recognized as a group of cytokine-inducible SH2 (CIS) domain proteins comprising eight family members in human (CIS and SOCS1-SOCS7). In addition to the SH2 domain, SOCS proteins have a variable N-terminal domain and a conserved SOCS box in the C-terminal domain. SOCS proteins bind to a substrate via their SH2 domain. The prototypical members, CIS and SOCS1-SOCS3, have been shown to regulate growth hormone signaling in vitro and in a classic negative feedback response compete for binding at phosphotyrosine sites in JAK kinase and receptor pathways to displace effector proteins and target bound receptors for proteasomal degradation. Loss of SOCS activity results in excessive cytokine signaling associated with a variety of hematopoietic, autoimmune, and inflammatory diseases and certain cancers. Members (SOCS4-SOCS7) were identified by their conserved SOCS box, an adapter motif of 3 helices that associates substrate binding domains, such as the SOCS SH2 domain, ankryin, and WD40 with ubiquitin ligase components. These show limited cytokine induction. In general SH2 domains are involved in signal transduction. They typically bind pTyr-containing ligands via two surface pockets, a pTyr and hydrophobic binding pocket, allowing proteins with SH2 domains to localize to tyrosine phosphorylated sites.


Pssm-ID: 198250  Cd Length: 100  Bit Score: 70.25  E-value: 1.16e-14
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 32455248 333 WYWGDISREEVNEKLRDTADGTFLVRDASTKMHgDYTLTLRKGGNNKLIKIFHRDGKYGF---SDPLTFSSVVELINHYR 409
Cdd:cd10387  12 WYWGPITRWEAEGKLANVPDGSFLVRDSSDDRY-LLSLSFRSHGKTLHTRIEHSNGRFSFyeqPDVEGHTSIVDLIEHSI 90

                ...
gi 32455248 410 NES 412
Cdd:cd10387  91 RDS 93
RhoGAP_nadrin cd04386
RhoGAP_nadrin: RhoGAP (GTPase-activator protein [GAP] for Rho-like small GTPases) domain of ...
141-295 1.66e-14

RhoGAP_nadrin: RhoGAP (GTPase-activator protein [GAP] for Rho-like small GTPases) domain of Nadrin-like proteins. Nadrin, also named Rich-1, has been shown to be involved in the regulation of Ca2+-dependent exocytosis in neurons and recently has been implicated in tight junction maintenance in mammalian epithelium. Small GTPases cluster into distinct families, and all act as molecular switches, active in their GTP-bound form but inactive when GDP-bound. The Rho family of GTPases activates effectors involved in a wide variety of developmental processes, including regulation of cytoskeleton formation, cell proliferation and the JNK signaling pathway. GTPases generally have a low intrinsic GTPase hydrolytic activity but there are family-specific groups of GAPs that enhance the rate of GTP hydrolysis by several orders of magnitude.


Pssm-ID: 239851  Cd Length: 203  Bit Score: 72.87  E-value: 1.66e-14
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 32455248 141 KKGLECSTLYRTQ-SSSNLAELRQLLDCDT--PSVDLEMIDVHVLADAFKRYLLDLPNPVIPAAVYSEMISLApEVQSSE 217
Cdd:cd04386  33 ETGMNEEGLFRVGgGASKLKRLKAALDAGTfsLPLDEFYSDPHAVASALKSYLRELPDPLLTYNLYEDWVQAA-NKPDED 111
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 32455248 218 EYIQLLKKLIRspSIPHQYWLTLQYLLKHFFKLSQTSSKNLLNARVLSEIFSPMLF-----RFSAASSDNTE-NLIKVIE 291
Cdd:cd04386 112 ERLQAIWRILN--KLPRENRDNLRYLIKFLSKLAQKSDENKMSPSNIAIVLAPNLLwakneGSLAEMAAGTSvHVVAIVE 189

                ....
gi 32455248 292 ILIS 295
Cdd:cd04386 190 LIIS 193
RhoGAP_GMIP cd04408
RhoGAP_GMIP: RhoGAP (GTPase-activator protein [GAP] for Rho-like small GTPases) domain of GMIP ...
125-274 1.99e-14

RhoGAP_GMIP: RhoGAP (GTPase-activator protein [GAP] for Rho-like small GTPases) domain of GMIP (Gem interacting protein). GMIP plays important roles in neurite growth and axonal guidance, and interacts with Gem, a member of the RGK subfamily of the Ras small GTPase superfamily, through the N-terminal half of the protein. GMIP contains a C-terminal RhoGAP domain. GMIP inhibits RhoA function, but is inactive towards Rac1 and Cdc41. Small GTPases cluster into distinct families, and all act as molecular switches, active in their GTP-bound form but inactive when GDP-bound. The Rho family of GTPases activates effectors involved in a wide variety of developmental processes, including regulation of cytoskeleton formation, cell proliferation and the JNK signaling pathway. GTPases generally have a low intrinsic GTPase hydrolytic activity but there are family-specific groups of GAPs that enhance the rate of GTP hydrolysis by several orders of magnitude.


Pssm-ID: 239873  Cd Length: 200  Bit Score: 72.54  E-value: 1.99e-14
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 32455248 125 PDIAPPLLIKLVEAIEKKGLECSTLYRTQSSSNLAE-LRQLLDCDTPSVDLEMIDVHVLADAFKRYLLDLPNPVIPAAVY 203
Cdd:cd04408  13 PEEVPFVVVRCTAEIENRALGVQGIYRISGSKARVEkLCQAFENGRDLVDLSGHSPHDITSVLKHFLKELPEPVLPFQLY 92
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 32455248 204 SEMISLAPEVQS-----------SEEYIQLLKKLIrsPSIPHQYWLTLQYLLKHFFKLSQTSSKNLLNARVLSEIFSPML 272
Cdd:cd04408  93 DDFIALAKELQRdsekaaespsiVENIIRSLKELL--GRLPVSNYNTLRHLMAHLYRVAERFEDNKMSPNNLGIVFGPTL 170

                ..
gi 32455248 273 FR 274
Cdd:cd04408 171 LR 172
RhoGAP_FAM13A1a cd04393
RhoGAP_FAM13A1a: RhoGAP (GTPase-activator protein [GAP] for Rho-like small GTPases) domain of ...
115-273 4.17e-14

RhoGAP_FAM13A1a: RhoGAP (GTPase-activator protein [GAP] for Rho-like small GTPases) domain of FAM13A1, isoform a-like proteins. The function of FAM13A1a is unknown. Small GTPases cluster into distinct families, and all act as molecular switches, active in their GTP-bound form but inactive when GDP-bound. The Rho family of GTPases activates effectors involved in a wide variety of developmental processes, including regulation of cytoskeleton formation, cell proliferation and the JNK signaling pathway. GTPases generally have a low intrinsic GTPase hydrolytic activity but there are family-specific groups of GAPs that enhance the rate of GTP hydrolysis by up several orders of magnitude.


Pssm-ID: 239858 [Multi-domain]  Cd Length: 189  Bit Score: 71.34  E-value: 4.17e-14
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 32455248 115 LPDLAEQFAPPDIAPPLLIKLVEAIEKKGLECSTLYRTQSSSNLAE-LRQLLDCDTPsVDL-EMIDVHVLADAFKRYLLD 192
Cdd:cd04393   7 LQELQQAGQPENGVPAVVRHIVEYLEQHGLEQEGLFRVNGNAETVEwLRQRLDSGEE-VDLsKEADVCSAASLLRLFLQE 85
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 32455248 193 LPNPVIPAAVYSEMISLAPEVQSSEEYIQLLKKLIRspSIPHQYWLTLQYLLKHFFKLSQTSSKNLLNARVLSEIFSPML 272
Cdd:cd04393  86 LPEGLIPASLQIRLMQLYQDYNGEDEFGRKLRDLLQ--QLPPVNYSLLKFLCHFLSNVASQHHENRMTAENLAAVFGPDV 163

                .
gi 32455248 273 F 273
Cdd:cd04393 164 F 164
RhoGAP_PARG1 cd04409
RhoGAP_PARG1: RhoGAP (GTPase-activator protein [GAP] for Rho-like small GTPases) domain of ...
125-294 8.98e-14

RhoGAP_PARG1: RhoGAP (GTPase-activator protein [GAP] for Rho-like small GTPases) domain of PARG1 (PTPL1-associated RhoGAP1). PARG1 was originally cloned as an interaction partner of PTPL1, an intracellular protein-tyrosine phosphatase. PARG1 interacts with Rap2, also a member of the Ras small GTPase superfamily whose exact function is unknown, and shows strong preference for Rho. Small GTPases cluster into distinct families, and all act as molecular switches, active in their GTP-bound form but inactive when GDP-bound. The Rho family of GTPases activates effectors involved in a wide variety of developmental processes, including regulation of cytoskeleton formation, cell proliferation and the JNK signaling pathway. GTPases generally have a low intrinsic GTPase hydrolytic activity but there are family-specific groups of GAPs that enhance the rate of GTP hydrolysis by several orders of magnitude.


Pssm-ID: 239874  Cd Length: 211  Bit Score: 70.99  E-value: 8.98e-14
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 32455248 125 PDIAPPLLIKLVEAIEKKGLECSTLYRTQ-SSSNLAELRQLLDCDTPSVDLEMIDVHVLADAFKRYLLDLPNPVIPAAVY 203
Cdd:cd04409  13 PDGIPFIIKKCTSEIESRALCLKGIYRVNgAKSRVEKLCQAFENGKDLVELSELSPHDISNVLKLYLRQLPEPLILFRLY 92
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 32455248 204 SEMISLAPEVQSSEEY---------------IQLLKKLIRSP----SIPHQYWLTLQYLLKHFFKLSQTSSKNLLNARVL 264
Cdd:cd04409  93 NEFIGLAKESQHVNETqeakknsdkkwpnmcTELNRILLKSKdllrQLPAPNYNTLQFLIVHLHRVSEQAEENKMSASNL 172
                       170       180       190
                ....*....|....*....|....*....|....*..
gi 32455248 265 SEIFSPMLFR-------FSAASSDNTENLIKVIEILI 294
Cdd:cd04409 173 GIIFGPTLIRprptdatVSLSSLVDYPHQARLVELLI 209
RhoGAP_ARHGAP22_24_25 cd04390
RhoGAP_ARHGAP22_24_25: GTPase-activator protein (GAP) domain for Rho-like GTPases found in ...
125-274 9.75e-14

RhoGAP_ARHGAP22_24_25: GTPase-activator protein (GAP) domain for Rho-like GTPases found in ARHGAP22, 24 and 25-like proteins; longer isoforms of these proteins contain an additional N-terminal pleckstrin homology (PH) domain. ARHGAP25 (KIA0053) has been identified as a GAP for Rac1 and Cdc42. Short isoforms (without the PH domain) of ARHGAP24, called RC-GAP72 and p73RhoGAP, and of ARHGAP22, called p68RacGAP, has been shown to be involved in angiogenesis and endothelial cell capillary formation. Small GTPases cluster into distinct families, and all act as molecular switches, active in their GTP-bound form but inactive when GDP-bound. The Rho family of GTPases activates effectors involved in a wide variety of developmental processes, including regulation of cytoskeleton formation, cell proliferation and the JNK signaling pathway. GTPases generally have a low intrinsic GTPase hydrolytic activity but there are family-specific groups of GAPs that enhance the rate of GTP hydrolysis by several orders of magnitude.


Pssm-ID: 239855 [Multi-domain]  Cd Length: 199  Bit Score: 70.55  E-value: 9.75e-14
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 32455248 125 PDIAPPLLIKLVEAIEKKGLECSTLYRTQSSSNLA-ELRQLLDC-DTPSVDLEMiDVHVLADAFKRYLLDLPNPVIPAAV 202
Cdd:cd04390  19 PRLVPILVEQCVDFIREHGLKEEGLFRLPGQANLVkQLQDAFDAgERPSFDSDT-DVHTVASLLKLYLRELPEPVIPWAQ 97
                        90       100       110       120       130       140       150
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 32455248 203 YSEMISLAPEVQSSEE--YIQLLKKLirsPSIPHQYWLTLQYLLKHFFKLSQTSSKNLLNARVLSEIFSPMLFR 274
Cdd:cd04390  98 YEDFLSCAQLLSKDEEkgLGELMKQV---SILPKVNYNLLSYICRFLDEVQSNSSVNKMSVQNLATVFGPNILR 168
SH2_csk_like cd09937
Src homology 2 (SH2) domain found in Carboxyl-Terminal Src Kinase (Csk); Both the C-terminal ...
333-412 1.42e-13

Src homology 2 (SH2) domain found in Carboxyl-Terminal Src Kinase (Csk); Both the C-terminal Src kinase (CSK) and CSK-homologous kinase (CHK) are members of the CSK-family of protein tyrosine kinases. These proteins suppress activity of Src-family kinases (SFK) by selectively phosphorylating the conserved C-terminal tail regulatory tyrosine by a similar mechanism. CHK is also capable of inhibiting SFKs by a non-catalytic mechanism that involves binding of CHK to SFKs to form stable protein complexes. The unphosphorylated form of SFKs is inhibited by CSK and CHK by a two-step mechanism. The first step involves the formation of a complex of SFKs with CSK/CHK with the SFKs in the complex are inactive. The second step, involves the phosphorylation of the C-terminal tail tyrosine of SFKs, which then dissociates and adopt an inactive conformation. The structural basis of how the phosphorylated SFKs dissociate from CSK/CHK to adopt the inactive conformation is not known. The inactive conformation of SFKs is stabilized by two intramolecular inhibitory interactions: (a) the pYT:SH2 interaction in which the phosphorylated C-terminal tail tyrosine (YT) binds to the SH2 domain, and (b) the linker:SH3 interaction of which the SH2-kinase domain linker binds to the SH3 domain. SFKs are activated by multiple mechanisms including binding of the ligands to the SH2 and SH3 domains to displace the two inhibitory intramolecular interactions, autophosphorylation, and dephosphorylation of YT. By selective phosphorylation and the non-catalytic inhibitory mechanism CSK and CHK are able to inhibit the active forms of SFKs. CSK and CHK are regulated by phosphorylation and inter-domain interactions. They both contain SH3, SH2, and kinase domains separated by the SH3-SH2 connector and SH2 kinase linker, intervening segments separating the three domains. They lack a conserved tyrosine phosphorylation site in the kinase domain and the C-terminal tail regulatory tyrosine phosphorylation site. The CSK SH2 domain is crucial for stabilizing the kinase domain in the active conformation. A disulfide bond here regulates CSK kinase activity. The subcellular localization and activity of CSK are regulated by its SH2 domain. In general SH2 domains are involved in signal transduction. They typically bind pTyr-containing ligands via two surface pockets, a pTyr and hydrophobic binding pocket, allowing proteins with SH2 domains to localize to tyrosine phosphorylated sites.


Pssm-ID: 198190  Cd Length: 98  Bit Score: 66.93  E-value: 1.42e-13
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 32455248 333 WYWGDISREEVNEKLRDTADGTFLVRDaSTKMHGDYTLTLRKGGNNKLIKIFHRDGKYGFSDPLTFSSVVELINHYRNES 412
Cdd:cd09937   5 WFHGKISREEAERLLQPPEDGLFLVRE-STNYPGDYTLCVSFEGKVEHYRVIYRNGKLTIDEEEYFENLIQLVEHYTKDA 83
RhoGAP_SYD1 cd04379
RhoGAP_SYD1: RhoGAP (GTPase-activator protein [GAP] for Rho-like small GTPases) domain present ...
113-280 3.38e-13

RhoGAP_SYD1: RhoGAP (GTPase-activator protein [GAP] for Rho-like small GTPases) domain present in SYD-1_like proteins. Syd-1, first identified and best studied in C.elegans, has been shown to play an important role in neuronal development by specifying axonal properties. Small GTPases cluster into distinct families, and all act as molecular switches, active in their GTP-bound form but inactive when GDP-bound. The Rho family of GTPases activates effectors involved in a wide variety of developmental processes, including regulation of cytoskeleton formation, cell proliferation and the JNK signaling pathway. GTPases generally have a low intrinsic GTPase hydrolytic activity but there are family-specific groups of GAPs that enhance the rate of GTP hydrolysis by several orders of magnitude.


Pssm-ID: 239844  Cd Length: 207  Bit Score: 69.03  E-value: 3.38e-13
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 32455248 113 LTLPDLAEQFAPPDIAPPLLIKLVEAIEKKGLECSTLYR-TQSSSNLAELRQLLDCDTPSVDL--EMI-DVHVLADAFKR 188
Cdd:cd04379   3 VPLSRLVEREGESRDVPIVLQKCVQEIERRGLDVIGLYRlCGSAAKKKELRDAFERNSAAVELseELYpDINVITGVLKD 82
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 32455248 189 YLLDLPNPVIPAAVYsEMISLAPEVQSSEEyIQLLKKLIRS--PSIPHQYWLTLQYLLKHFFKLSQTSSKNLLNARVLSE 266
Cdd:cd04379  83 YLRELPEPLITPQLY-EMVLEALAVALPND-VQTNTHLTLSiiDCLPLSAKATLLLLLDHLSLVLSNSERNKMTPQNLAV 160
                       170
                ....*....|....
gi 32455248 267 IFSPMLFRFSAASS 280
Cdd:cd04379 161 CFGPVLMFCSQEFS 174
SH2_Tec_family cd09934
Src homology 2 (SH2) domain found in Tec-like proteins; The Tec protein tyrosine kinase is the ...
624-702 8.98e-13

Src homology 2 (SH2) domain found in Tec-like proteins; The Tec protein tyrosine kinase is the founding member of a family that includes Btk, Itk, Bmx, and Txk. The members have a PH domain, a zinc-binding motif, a SH3 domain, a SH2 domain, and a protein kinase catalytic domain. Btk is involved in B-cell receptor signaling with mutations in Btk responsible for X-linked agammaglobulinemia (XLA) in humans and X-linked immunodeficiency (xid) in mice. Itk is involved in T-cell receptor signaling. Tec is expressed in both T and B cells, and is thought to function in activated and effector T lymphocytes to induce the expression of genes regulated by NFAT transcription factors. In general SH2 domains are involved in signal transduction. They typically bind pTyr-containing ligands via two surface pockets, a pTyr and hydrophobic binding pocket, allowing proteins with SH2 domains to localize to tyrosine phosphorylated sites.


Pssm-ID: 198188  Cd Length: 104  Bit Score: 65.11  E-value: 8.98e-13
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 32455248 624 WNVGSSNRNKAENLLRGK-RDGTFLVRESSKQGCYACSV----VVDGEVKHCVINKTATG-YGFAEPYnLYSSLKELVLH 697
Cdd:cd09934   8 WYVGDMSRQRAESLLKQEdKEGCFVVRNSSTKGLYTVSLftkvPGSPHVKHYHIKQNARSeFYLAEKH-CFETIPELINY 86

                ....*
gi 32455248 698 YQHTS 702
Cdd:cd09934  87 HQHNS 91
SH2_SOCS2 cd10383
Src homology 2 (SH2) domain found in suppressor of cytokine signaling (SOCS) proteins; SH2 ...
327-408 1.17e-12

Src homology 2 (SH2) domain found in suppressor of cytokine signaling (SOCS) proteins; SH2 domain found in SOCS proteins. SOCS was first recognized as a group of cytokine-inducible SH2 (CIS) domain proteins comprising eight family members in human (CIS and SOCS1-SOCS7). In addition to the SH2 domain, SOCS proteins have a variable N-terminal domain and a conserved SOCS box in the C-terminal domain. SOCS proteins bind to a substrate via their SH2 domain. The prototypical members, CIS and SOCS1-SOCS3, have been shown to regulate growth hormone signaling in vitro and in a classic negative feedback response compete for binding at phosphotyrosine sites in JAK kinase and receptor pathways to displace effector proteins and target bound receptors for proteasomal degradation. Loss of SOCS activity results in excessive cytokine signaling associated with a variety of hematopoietic, autoimmune, and inflammatory diseases and certain cancers. Members (SOCS4-SOCS7) were identified by their conserved SOCS box, an adapter motif of 3 helices that associates substrate binding domains, such as the SOCS SH2 domain, ankryin, and WD40 with ubiquitin ligase components. These show limited cytokine induction. In general SH2 domains are involved in signal transduction. They typically bind pTyr-containing ligands via two surface pockets, a pTyr and hydrophobic binding pocket, allowing proteins with SH2 domains to localize to tyrosine phosphorylated sites.


Pssm-ID: 198246  Cd Length: 103  Bit Score: 64.52  E-value: 1.17e-12
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 32455248 327 SLQDAEWYWGDISREEVNEKLRDTADGTFLVRDAStkmHGDYTLTL----RKGGNNklIKIFHRDGKYGFsDPLT----- 397
Cdd:cd10383   3 ELSQTGWYWGSMTVNEAKEKLQDAPEGTFLVRDSS---HSDYLLTIsvktSAGPTN--LRIEYQDGKFRL-DSIIcvksk 76
                        90
                ....*....|....
gi 32455248 398 ---FSSVVELINHY 408
Cdd:cd10383  77 lkqFDSVVHLIEYY 90
SH2_CIS cd10718
Src homology 2 (SH2) domain found in cytokine-inducible SH2-containing protein (CIS); CIS ...
328-408 1.78e-12

Src homology 2 (SH2) domain found in cytokine-inducible SH2-containing protein (CIS); CIS family members are known to be cytokine-inducible negative regulators of cytokine signaling. The expression of the CIS gene can be induced by IL2, IL3, GM-CSF and EPO in hematopoietic cells. Proteasome-mediated degradation of this protein has been shown to be involved in the inactivation of the erythropoietin receptor. Suppressor of cytokine signalling (SOCS) was first recognized as a group of cytokine-inducible SH2 (CIS) domain proteins comprising eight family members in human (CIS and SOCS1-SOCS7). In addition to the SH2 domain, SOCS proteins have a variable N-terminal domain and a conserved SOCS box in the C-terminal domain. SOCS proteins bind to a substrate via their SH2 domain. The prototypical members, CIS and SOCS1-SOCS3, have been shown to regulate growth hormone signaling in vitro and in a classic negative feedback response compete for binding at phosphotyrosine sites in JAK kinase and receptor pathways to displace effector proteins and target bound receptors for proteasomal degradation. Loss of SOCS activity results in excessive cytokine signaling associated with a variety of hematopoietic, autoimmune, and inflammatory diseases and certain cancers. In general SH2 domains are involved in signal transduction. They typically bind pTyr-containing ligands via two surface pockets, a pTyr and hydrophobic binding pocket, allowing proteins with SH2 domains to localize to tyrosine phosphorylated sites.


Pssm-ID: 198285  Cd Length: 88  Bit Score: 63.62  E-value: 1.78e-12
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 32455248 328 LQDAEWYWGDISREEVNEKLRDTADGTFLVRDAStkmHGDYTLTL----RKGGNNklIKIFHRDGKY-------GFSDPL 396
Cdd:cd10718   1 LRESGWYWGSITASEAHQALQKAPEGTFLVRDSS---HPSYMLTLsvktTRGPTN--VRIEYSDGSFrldssslARPRLL 75
                        90
                ....*....|..
gi 32455248 397 TFSSVVELINHY 408
Cdd:cd10718  76 SFPDVVSLVQHY 87
SH2_ABL cd09935
Src homology 2 (SH2) domain found in Abelson murine lymphosarcoma virus (ABL) proteins; ...
620-717 3.04e-12

Src homology 2 (SH2) domain found in Abelson murine lymphosarcoma virus (ABL) proteins; ABL-family proteins are highly conserved tyrosine kinases. Each ABL protein contains an SH3-SH2-TK (Src homology 3-Src homology 2-tyrosine kinase) domain cassette, which confers autoregulated kinase activity and is common among nonreceptor tyrosine kinases. Several types of posttranslational modifications control ABL catalytic activity, subcellular localization, and stability, with consequences for both cytoplasmic and nuclear ABL functions. Binding partners provide additional regulation of ABL catalytic activity, substrate specificity, and downstream signaling. By combining this cassette with actin-binding and -bundling domain, ABL proteins are capable of connecting phosphoregulation with actin-filament reorganization. Vertebrate paralogs, ABL1 and ABL2, have evolved to perform specialized functions. ABL1 includes nuclear localization signals and a DNA binding domain which is used to mediate DNA damage-repair functions, while ABL2 has additional binding capacity for actin and for microtubules to enhance its cytoskeletal remodeling functions. SH2 is involved in several autoinhibitory mechanism that constrain the enzymatic activity of the ABL-family kinases. In one mechanism SH2 and SH3 cradle the kinase domain while a cap sequence stabilizes the inactive conformation resulting in a locked inactive state. Another involves phosphatidylinositol 4,5-bisphosphate (PIP2) which binds the SH2 domain through residues normally required for phosphotyrosine binding in the linker segment between the SH2 and kinase domains. The SH2 domain contributes to ABL catalytic activity and target site specificity. It is thought that the ABL catalytic site and SH2 pocket have coevolved to recognize the same sequences. Recent work now supports a hierarchical processivity model in which the substrate target site most compatible with ABL kinase domain preferences is phosphorylated with greatest efficiency. If this site is compatible with the ABL SH2 domain specificity, it will then reposition and dock in the SH2 pocket. This mechanism also explains how ABL kinases phosphorylates poor targets on the same substrate if they are properly positioned and how relatively poor substrate proteins might be recruited to ABL through a complex with strong substrates that can also dock with the SH2 pocket. In general SH2 domains are involved in signal transduction. They typically bind pTyr-containing ligands via two surface pockets, a pTyr and hydrophobic binding pocket, allowing proteins with SH2 domains to localize to tyrosine phosphorylated sites.


Pssm-ID: 198189  Cd Length: 94  Bit Score: 63.18  E-value: 3.04e-12
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 32455248 620 DEKTWNVGSSNRNKAENLLRGKRDGTFLVRES-SKQGCYACSVVVDGEVKHCVINKTATGYGFAEPYNLYSSLKELVLHY 698
Cdd:cd09935   1 EKHSWYHGPISRNAAEYLLSSGINGSFLVRESeSSPGQYSISLRYDGRVYHYRISEDSDGKVYVTQEHRFNTLAELVHHH 80
                        90
                ....*....|....*....
gi 32455248 699 QhtslvQHNDSLNVTLAYP 717
Cdd:cd09935  81 S-----KNADGLITTLRYP 94
RhoGAP_ARHGAP20 cd04402
RhoGAP_ARHGAP20: RhoGAP (GTPase-activator protein [GAP] for Rho-like small GTPases) domain of ...
115-295 4.08e-12

RhoGAP_ARHGAP20: RhoGAP (GTPase-activator protein [GAP] for Rho-like small GTPases) domain of ArhGAP20-like proteins. ArhGAP20, also known as KIAA1391 and RA-RhoGAP, contains a RhoGAP, a RA, and a PH domain, and ANXL repeats. ArhGAP20 is activated by Rap1 and induces inactivation of Rho, which in turn leads to neurite outgrowth. Small GTPases cluster into distinct families, and all act as molecular switches, active in their GTP-bound form but inactive when GDP-bound. The Rho family of GTPases activates effectors involved in a wide variety of developmental processes, including regulation of cytoskeleton formation, cell proliferation and the JNK signaling pathway. GTPases generally have a low intrinsic GTPase hydrolytic activity but there are family-specific groups of GAPs that enhance the rate of GTP hydrolysis by several orders of magnitude.


Pssm-ID: 239867  Cd Length: 192  Bit Score: 65.40  E-value: 4.08e-12
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 32455248 115 LPDLAEQFAPPdiaPPLLIKLVeAIEKKGLECSTLYRTQSS-SNLAELRQLLDCDTpSVDLEMIDVHVLADAFKRYLLDL 193
Cdd:cd04402   6 LSNICEDDNLP---KPILDMLS-LLYQKGPSTEGIFRRSANaKACKELKEKLNSGV-EVDLKAEPVLLLASVLKDFLRNI 80
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 32455248 194 PNPVIPAAVYSEMISlAPEVQSSEEYIQLLKKLIRspSIPHQYWLTLQYLLKHFFKLSQTSSKNLLNARVLSEIFSPMLF 273
Cdd:cd04402  81 PGSLLSSDLYEEWMS-ALDQENEEEKIAELQRLLD--KLPRPNVLLLKHLICVLHNISQNSETNKMDAFNLAVCIAPSLL 157
                       170       180
                ....*....|....*....|....*
gi 32455248 274 RFSAASS---DNTENLIKVIEILIS 295
Cdd:cd04402 158 WPPASSElqnEDLKKVTSLVQFLIE 182
RhoGAP_CdGAP cd04384
RhoGAP_CdGAP: RhoGAP (GTPase-activator protein [GAP] for Rho-like small GTPases) domain of ...
129-274 2.04e-11

RhoGAP_CdGAP: RhoGAP (GTPase-activator protein [GAP] for Rho-like small GTPases) domain of CdGAP-like proteins; CdGAP contains an N-terminal RhoGAP domain and a C-terminal proline-rich region, and it is active on both Cdc42 and Rac1 but not RhoA. CdGAP is recruited to focal adhesions via the interaction with the scaffold protein actopaxin (alpha-parvin). Small GTPases cluster into distinct families, and all act as molecular switches, active in their GTP-bound form but inactive when GDP-bound. The Rho family of GTPases activates effectors involved in a wide variety of developmental processes, including regulation of cytoskeleton formation, cell proliferation and the JNK signaling pathway. GTPases generally have a low intrinsic GTPase hydrolytic activity but there are family-specific groups of GAPs that enhance the rate of GTP hydrolysis by several orders of magnitude.


Pssm-ID: 239849 [Multi-domain]  Cd Length: 195  Bit Score: 63.68  E-value: 2.04e-11
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 32455248 129 PPLLIKLVEAIEKKGLeCSTLYRTQS-SSNLAELRQLLDCD-TPSV--DLEMIDVHVLADAFKRYLLDLPNPVIPAAVYs 204
Cdd:cd04384  19 PQVLKSCTEFIEKHGI-VDGIYRLSGiASNIQRLRHEFDSEqIPDLtkDVYIQDIHSVSSLCKLYFRELPNPLLTYQLY- 96
                        90       100       110       120       130       140       150
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 32455248 205 EMISLAPEVQSSEEYIQLLKKLIRSPSIPHqyWLTLQYLLKHFFKLSQTSSKNLLNARVLSEIFSPMLFR 274
Cdd:cd04384  97 EKFSEAVSAASDEERLEKIHDVIQQLPPPH--YRTLEFLMRHLSRLAKYCSITNMHAKNLAIVWAPNLLR 164
SH2_SOCS7 cd10388
Src homology 2 (SH2) domain found in suppressor of cytokine signaling (SOCS) proteins; SH2 ...
327-405 2.08e-11

Src homology 2 (SH2) domain found in suppressor of cytokine signaling (SOCS) proteins; SH2 domain found in SOCS proteins. SOCS was first recognized as a group of cytokine-inducible SH2 (CIS) domain proteins comprising eight family members in human (CIS and SOCS1-SOCS7). In addition to the SH2 domain, SOCS proteins have a variable N-terminal domain and a conserved SOCS box in the C-terminal domain. SOCS proteins bind to a substrate via their SH2 domain. The prototypical members, CIS and SOCS1-SOCS3, have been shown to regulate growth hormone signaling in vitro and in a classic negative feedback response compete for binding at phosphotyrosine sites in JAK kinase and receptor pathways to displace effector proteins and target bound receptors for proteasomal degradation. Loss of SOCS activity results in excessive cytokine signaling associated with a variety of hematopoietic, autoimmune, and inflammatory diseases and certain cancers. Members (SOCS4-SOCS7) were identified by their conserved SOCS box, an adapter motif of 3 helices that associates substrate binding domains, such as the SOCS SH2 domain, ankryin, and WD40 with ubiquitin ligase components. These show limited cytokine induction. In general SH2 domains are involved in signal transduction. They typically bind pTyr-containing ligands via two surface pockets, a pTyr and hydrophobic binding pocket, allowing proteins with SH2 domains to localize to tyrosine phosphorylated sites.


Pssm-ID: 198251  Cd Length: 101  Bit Score: 60.83  E-value: 2.08e-11
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 32455248 327 SLQDAEWYWGDISREEVNEKLRDTADGTFLVRDASTKMHgDYTLTLRKGGNNKLIKIFHRDGKYGFSDPLTFS----SVV 402
Cdd:cd10388   6 ELKDCGWYWGPMSWEDAEKVLSNKPDGSFLVRDSSDDRY-IFSLSFRSQGSVHHTRIEQYQGTFSLGSRNKFVdrsqSLV 84

                ...
gi 32455248 403 ELI 405
Cdd:cd10388  85 EFI 87
SH2_BLNK_SLP-76 cd09929
Src homology 2 (SH2) domain found in B-cell linker (BLNK) protein and SH2 domain-containing ...
327-428 2.95e-11

Src homology 2 (SH2) domain found in B-cell linker (BLNK) protein and SH2 domain-containing leukocyte protein of 76 kDa (SLP-76); BLNK (also known as SLP-65 or BASH) is an important adaptor protein expressed in B-lineage cells. BLNK consists of a N-terminal sterile alpha motif (SAM) domain and a C-terminal SH2 domain. BLNK is a cytoplasmic protein, but a part of it is bound to the plasma membrane through an N-terminal leucine zipper motif and transiently bound to a cytoplasmic domain of Iga through its C-terminal SH2 domain upon B cell antigen receptor (BCR)-stimulation. A non-ITAM phosphotyrosine in Iga is necessary for the binding with the BLNK SH2 domain and/or for normal BLNK function in signaling and B cell activation. Upon phosphorylation BLNK binds Btk and PLCgamma2 through their SH2 domains and mediates PLCgamma2 activation by Btk. BLNK also binds other signaling molecules such as Vav, Grb2, Syk, and HPK1. BLNK has been shown to be necessary for BCR-mediated Ca2+ mobilization, for the activation of mitogen-activated protein kinases such as ERK, JNK, and p38 in a chicken B cell line DT40, and for activation of transcription factors such as NF-AT and NF-kappaB in human or mouse B cells. BLNK is involved in B cell development, B cell survival, activation, proliferation, and T-independent immune responses. BLNK is structurally homologous to SLP-76. SLP-76 and (linker for activation of T cells) LAT are adaptor/linker proteins in T cell antigen receptor activation and T cell development. BLNK interacts with many downstream signaling proteins that interact directly with both SLP-76 and LAT. New data suggest functional complementation of SLP-76 and LAT in T cell antigen receptor function with BLNK in BCR function. In general SH2 domains are involved in signal transduction. They typically bind pTyr-containing ligands via two surface pockets, a pTyr and hydrophobic binding pocket, allowing proteins with SH2 domains to localize to tyrosine phosphorylated sites.


Pssm-ID: 198183  Cd Length: 121  Bit Score: 61.18  E-value: 2.95e-11
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 32455248 327 SLQDAEWYWGDISREEVNEKLRDTA-DGTFLVRDASTKmHGDYTLTLRKGGNNKL--IKIFHRDGKYGFSdpL------- 396
Cdd:cd09929   7 DLLPKEWYAGNIDRKEAEEALRRSNkDGTFLVRDSSGK-DSSQPYTLMVLYNDKVynIQIRFLENTRQYA--Lgtglrge 83
                        90       100       110
                ....*....|....*....|....*....|....*..
gi 32455248 397 -TFSSVVELINHYRNESL----AQYNPKLDVKLLYPV 428
Cdd:cd09929  84 eTFSSVAEIIEHHQKTPLllidGKDNTKDSTCLLYAA 120
SH2_Vav3 cd10407
Src homology 2 (SH2) domain found in the Vav3 proteins; Proto-oncogene vav is a member of the ...
333-427 4.24e-11

Src homology 2 (SH2) domain found in the Vav3 proteins; Proto-oncogene vav is a member of the Dbl family of guanine nucleotide exchange factors (GEF) for the Rho family of GTP binding proteins. All vavs are activated by tyrosine phosphorylation leading to their activation. There are three Vav mammalian family members: Vav1 which is expressed in the hematopoietic system, and Vav2 and Vav3 are more ubiquitously expressed. Vav3 preferentially activates RhoA, RhoG and, to a lesser extent, Rac1. Alternatively spliced transcript variants encoding different isoforms have been described for this gene. VAV3 has been shown to interact with Grb2. Vav proteins are involved in several processes that require cytoskeletal reorganization, such as the formation of the immunological synapse (IS), phagocytosis, platelet aggregation, spreading, and transformation. Vavs function as guanine nucleotide exchange factors (GEFs) for the Rho/Rac family of GTPases. Vav family members have several conserved motifs/domains including: a leucine-rich region, a leucine-zipper, a calponin homology (CH) domain, an acidic domain, a Dbl-homology (DH) domain, a pleckstrin homology (PH) domain, a cysteine-rich domain, 2 SH3 domains, a proline-rich region, and a SH2 domain. Vavs are the only known Rho GEFs that have both the DH/PH motifs and SH2/SH3 domains in the same protein. The leucine-rich helix-loop-helix (HLH) domain is thought to be involved in protein heterodimerization with other HLH proteins and it may function as a negative regulator by forming inactive heterodimers. The CH domain is usually involved in the association with filamentous actin, but in Vav it controls NFAT stimulation, Ca2+ mobilization, and its transforming activity. Acidic domains are involved in protein-protein interactions and contain regulatory tyrosines. The DH domain is a GDP-GTP exchange factor on Rho/Rac GTPases. The PH domain in involved in interactions with GTP-binding proteins, lipids and/or phosphorylated serine/threonine residues. The SH3 domain is involved in localization of proteins to specific sites within the cell interacting with protein with proline-rich sequences. The SH2 domain mediates a high affinity interaction with tyrosine phosphorylated proteins. In general SH2 domains are involved in signal transduction. They typically bind pTyr-containing ligands via two surface pockets, a pTyr and hydrophobic binding pocket, allowing proteins with SH2 domains to localize to tyrosine phosphorylated sites.


Pssm-ID: 198270  Cd Length: 103  Bit Score: 60.02  E-value: 4.24e-11
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 32455248 333 WYWGDISREEVNEKLRDTADGTFLVRDaSTKMHGDYTLTLRKGGNNKLIKIFHRDGKYGFSDPLTFSSVVELINHYRNES 412
Cdd:cd10407   7 WYAGAMERLQAETELINRVNSTYLVRH-RTKESGEYAISIKYNNEVKHIKILTRDGFFHIAENRKFKSLMELVEYYKHHS 85
                        90
                ....*....|....*
gi 32455248 413 LAQYNPKLDVKLLYP 427
Cdd:cd10407  86 LKEGFRSLDTTLQFP 100
SH2_C-SH2_PLC_gamma_like cd09932
C-terminal Src homology 2 (C-SH2) domain in Phospholipase C gamma; Phospholipase C gamma is a ...
619-718 4.78e-11

C-terminal Src homology 2 (C-SH2) domain in Phospholipase C gamma; Phospholipase C gamma is a signaling molecule that is recruited to the C-terminal tail of the receptor upon autophosphorylation of a highly conserved tyrosine. PLCgamma is composed of a Pleckstrin homology (PH) domain followed by an elongation factor (EF) domain, 2 catalytic regions of PLC domains that flank 2 tandem SH2 domains (N-SH2, C-SH2), and ending with a SH3 domain and C2 domain. N-SH2 SH2 domain-mediated interactions represent a crucial step in transmembrane signaling by receptor tyrosine kinases. SH2 domains recognize phosphotyrosine (pY) in the context of particular sequence motifs in receptor phosphorylation sites. Both N-SH2 and C-SH2 have a very similar binding affinity to pY. But in growth factor stimulated cells these domains bind to different target proteins. N-SH2 binds to pY containing sites in the C-terminal tails of tyrosine kinases and other receptors. Recently it has been shown that this interaction is mediated by phosphorylation-independent interactions between a secondary binding site found exclusively on the N-SH2 domain and a region of the FGFR1 tyrosine kinase domain. This secondary site on the SH2 cooperates with the canonical pY site to regulate selectivity in mediating a specific cellular process. C-SH2 binds to an intramolecular site on PLCgamma itself which allows it to hydrolyze phosphatidylinositol-4,5-bisphosphate into diacylglycerol and inositol triphosphate. These then activate protein kinase C and release calcium. In general SH2 domains are involved in signal transduction. They typically bind pTyr-containing ligands via two surface pockets, a pTyr and hydrophobic binding pocket, allowing proteins with SH2 domains to localize to tyrosine phosphorylated sites.


Pssm-ID: 198186  Cd Length: 104  Bit Score: 59.97  E-value: 4.78e-11
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 32455248 619 HDEKTWNVGSSNRNKAENLL-RGKRDGTFLVRESSK-QGCYACSVVVDGEVKHCVINKTATGY--GFAEpynlYSSLKEL 694
Cdd:cd09932   1 HESKEWFHANLTREQAEEMLmRVPRDGAFLVRPSETdPNSFAISFRAEGKIKHCRIKQEGRLFviGTSQ----FESLVEL 76
                        90       100
                ....*....|....*....|....
gi 32455248 695 VLHYQHTSLVQhndslNVTLAYPV 718
Cdd:cd09932  77 VSYYEKHPLYR-----KIKLRYPV 95
SH2_Tec_family cd09934
Src homology 2 (SH2) domain found in Tec-like proteins; The Tec protein tyrosine kinase is the ...
327-429 5.45e-11

Src homology 2 (SH2) domain found in Tec-like proteins; The Tec protein tyrosine kinase is the founding member of a family that includes Btk, Itk, Bmx, and Txk. The members have a PH domain, a zinc-binding motif, a SH3 domain, a SH2 domain, and a protein kinase catalytic domain. Btk is involved in B-cell receptor signaling with mutations in Btk responsible for X-linked agammaglobulinemia (XLA) in humans and X-linked immunodeficiency (xid) in mice. Itk is involved in T-cell receptor signaling. Tec is expressed in both T and B cells, and is thought to function in activated and effector T lymphocytes to induce the expression of genes regulated by NFAT transcription factors. In general SH2 domains are involved in signal transduction. They typically bind pTyr-containing ligands via two surface pockets, a pTyr and hydrophobic binding pocket, allowing proteins with SH2 domains to localize to tyrosine phosphorylated sites.


Pssm-ID: 198188  Cd Length: 104  Bit Score: 59.72  E-value: 5.45e-11
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 32455248 327 SLQDAEWYWGDISREEVNEKLRDTA-DGTFLVRDASTKmhGDYTLTL-RKGGNNKLIKIFH----RDGKYGFSDPLTFSS 400
Cdd:cd09934   2 NLEKYEWYVGDMSRQRAESLLKQEDkEGCFVVRNSSTK--GLYTVSLfTKVPGSPHVKHYHikqnARSEFYLAEKHCFET 79
                        90       100       110
                ....*....|....*....|....*....|
gi 32455248 401 VVELINHYrneslaQYNPK-LDVKLLYPVS 429
Cdd:cd09934  80 IPELINYH------QHNSGgLATRLKYPVC 103
SH2_Src_family cd09933
Src homology 2 (SH2) domain found in the Src family of non-receptor tyrosine kinases; The Src ...
332-412 5.80e-11

Src homology 2 (SH2) domain found in the Src family of non-receptor tyrosine kinases; The Src family kinases are nonreceptor tyrosine kinases that have been implicated in pathways regulating proliferation, angiogenesis, invasion and metastasis, and bone metabolism. It is thought that transforming ability of Src is linked to its ability to activate key signaling molecules in these pathways, rather than through direct activity. As such blocking Src activation has been a target for drug companies. Src family members can be divided into 3 groups based on their expression pattern: 1) Src, Fyn, and Yes; 2) Blk, Fgr, Hck, Lck, and Lyn; and 3) Frk-related kinases Frk/Rak and Iyk/Bsk Of these, cellular c-Src is the best studied and most frequently implicated in oncogenesis. The c-Src contains five distinct regions: a unique N-terminal domain, an SH3 domain, an SH2 domain, a kinase domain and a regulatory tail, as do the other members of the family. Src exists in both active and inactive conformations. Negative regulation occurs through phosphorylation of Tyr, resulting in an intramolecular association between phosphorylated Tyr and the SH2 domain of SRC, which locks the protein in a closed conformation. Further stabilization of the inactive state occurs through interactions between the SH3 domain and a proline-rich stretch of residues within the kinase domain. Conversely, dephosphorylation of Tyr allows SRC to assume an open conformation. Full activity requires additional autophosphorylation of a Tyr residue within the catalytic domain. Loss of the negative-regulatory C-terminal segment has been shown to result in increased activity and transforming potential. Phosphorylation of the C-terminal Tyr residue by C-terminal Src kinase (Csk) and Csk homology kinase results in increased intramolecular interactions and consequent Src inactivation. Specific phosphatases, protein tyrosine phosphatase a (PTPa) and the SH-containing phosphatases SHP1/SHP2, have also been shown to take a part in Src activation. Src is also activated by direct binding of focal adhesion kinase (Fak) and Crk-associated substrate (Cas) to the SH2 domain. SRC activity can also be regulated by numerous receptor tyrosine kinases (RTKs), such as Her2, epidermal growth factor receptor (EGFR), fibroblast growth factor receptor, platelet-derived growth factor receptor (PDGFR), and vascular endothelial growth factor receptor (VEGFR). In general SH2 domains are involved in signal transduction. They typically bind pTyr-containing ligands via two surface pockets, a pTyr and hydrophobic binding pocket, allowing proteins with SH2 domains to localize to tyrosine phosphorylated sites.


Pssm-ID: 199827  Cd Length: 101  Bit Score: 59.52  E-value: 5.80e-11
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 32455248 332 EWYWGDISREEVNEKL--RDTADGTFLVRDASTKmHGDYTLTLR-----KGGNNKLIKIFHRD-GKYGFSDPLTFSSVVE 403
Cdd:cd09933   4 EWFFGKIKRKDAEKLLlaPGNPRGTFLIRESETT-PGAYSLSVRdgddaRGDTVKHYRIRKLDnGGYYITTRATFPTLQE 82

                ....*....
gi 32455248 404 LINHYRNES 412
Cdd:cd09933  83 LVQHYSKDA 91
RhoGAP_Bcr cd04387
RhoGAP_Bcr: RhoGAP (GTPase-activator protein [GAP] for Rho-like small GTPases) domain of Bcr ...
129-290 9.43e-11

RhoGAP_Bcr: RhoGAP (GTPase-activator protein [GAP] for Rho-like small GTPases) domain of Bcr (breakpoint cluster region protein)-like proteins. Bcr is a multidomain protein with a variety of enzymatic functions. It contains a RhoGAP and a Rho GEF domain, a Ser/Thr kinase domain, an N-terminal oligomerization domain, and a C-terminal PDZ binding domain, in addition to PH and C2 domains. Bcr is a negative regulator of: i) RacGTPase, via the Rho GAP domain, ii) the Ras-Raf-MEK-ERK pathway, via phosphorylation of the Ras binding protein AF-6, and iii) the Wnt signaling pathway through binding beta-catenin. Bcr can form a complex with beta-catenin and Tcf1. The Wnt signaling pathway is involved in cell proliferation, differentiation, and cell renewal. Bcr was discovered as a fusion partner of Abl. The Bcr-Abl fusion is characteristic for a large majority of chronic myelogenous leukemias (CML). Small GTPases cluster into distinct families, and all act as molecular switches, active in their GTP-bound form but inactive when GDP-bound. The Rho family of GTPases activates effectors involved in a wide variety of developmental processes, including regulation of cytoskeleton formation, cell proliferation and the JNK signaling pathway. GTPases generally have a low intrinsic GTPase hydrolytic activity but there are family-specific groups of GAPs that enhance the rate of GTP hydrolysis by several orders of magnitude.


Pssm-ID: 239852 [Multi-domain]  Cd Length: 196  Bit Score: 61.87  E-value: 9.43e-11
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 32455248 129 PPLLIKLVEAIEKKGLECSTLYRTQS-SSNLAELRQLLDCDTPSVDLEM--IDVHVLADAFKRYLLDLPNPVIPAAVYSE 205
Cdd:cd04387  17 PYIVRQCVEEVERRGMEEVGIYRISGvATDIQALKAAFDTNNKDVSVMLseMDVNAIAGTLKLYFRELPEPLFTDELYPN 96
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 32455248 206 M---ISLAPEVQSSEEYIQLLKklirspSIPHQYWLTLQYLLKHFFKLSQTSSKNLLNARVLSEIFSPMLFRFSAASSDN 282
Cdd:cd04387  97 FaegIALSDPVAKESCMLNLLL------SLPDPNLVTFLFLLHHLKRVAEREEVNKMSLHNLATVFGPTLLRPSEKESKI 170

                ....*...
gi 32455248 283 TENLIKVI 290
Cdd:cd04387 171 PTNTMTDS 178
SH2_Nck_family cd09943
Src homology 2 (SH2) domain found in the Nck family; Nck proteins are adaptors that modulate ...
332-409 1.08e-10

Src homology 2 (SH2) domain found in the Nck family; Nck proteins are adaptors that modulate actin cytoskeleton dynamics by linking proline-rich effector molecules to tyrosine kinases or phosphorylated signaling intermediates. There are two members known in this family: Nck1 (Nckalpha) and Nck2 (Nckbeta and Growth factor receptor-bound protein 4 (Grb4)). They are characterized by having 3 SH3 domains and a C-terminal SH2 domain. Nck1 and Nck2 have overlapping functions as determined by gene knockouts. Both bind receptor tyrosine kinases and other tyrosine-phosphorylated proteins through their SH2 domains. In addition they also bind distinct targets. Neuronal signaling proteins: EphrinB1, EphrinB2, and Disabled-1 (Dab-1) all bind to Nck-2 exclusively. And in the case of PDGFR, Tyr(P)751 binds to Nck1 while Tyr(P)1009 binds to Nck2. Nck1 and Nck2 have a role in the infection process of enteropathogenic Escherichia coli (EPEC). Their SH3 domains are involved in recruiting and activating the N-WASP/Arp2/3 complex inducing actin polymerization resulting in the production of pedestals, dynamic bacteria-presenting protrusions of the plasma membrane. A similar thing occurs in the vaccinia virus where motile plasma membrane projections are formed beneath the virus. Recently it has been shown that the SH2 domains of both Nck1 and Nck2 bind the G-protein coupled receptor kinase-interacting protein 1 (GIT1) in a phosphorylation-dependent manner. In general SH2 domains are involved in signal transduction. They typically bind pTyr-containing ligands via two surface pockets, a pTyr and hydrophobic binding pocket, allowing proteins with SH2 domains to localize to tyrosine phosphorylated sites.


Pssm-ID: 198196  Cd Length: 93  Bit Score: 58.68  E-value: 1.08e-10
                        10        20        30        40        50        60        70
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 32455248 332 EWYWGDISREEVNEKLRDTA-DGTFLVRDASTKMhGDYTLTLRKGGNNKLIKIFHRDGKYGFSDPlTFSSVVELINHYR 409
Cdd:cd09943   2 PWYYGRITRHQAETLLNEHGhEGDFLIRDSESNP-GDYSVSLKAPGRNKHFKVQVVDNVYCIGQR-KFHTMDELVEHYK 78
SH2_N-SH2_PLC_gamma_like cd10341
N-terminal Src homology 2 (N-SH2) domain in Phospholipase C gamma; Phospholipase C gamma is a ...
332-413 9.93e-10

N-terminal Src homology 2 (N-SH2) domain in Phospholipase C gamma; Phospholipase C gamma is a signaling molecule that is recruited to the C-terminal tail of the receptor upon autophosphorylation of a highly conserved tyrosine. PLCgamma is composed of a Pleckstrin homology (PH) domain followed by an elongation factor (EF) domain, 2 catalytic regions of PLC domains that flank 2 tandem SH2 domains (N-SH2, C-SH2), and ending with a SH3 domain and C2 domain. N-SH2 SH2 domain-mediated interactions represent a crucial step in transmembrane signaling by receptor tyrosine kinases. SH2 domains recognize phosphotyrosine (pY) in the context of particular sequence motifs in receptor phosphorylation sites. Both N-SH2 and C-SH2 have a very similar binding affinity to pY. But in growth factor stimulated cells these domains bind to different target proteins. N-SH2 binds to pY containing sites in the C-terminal tails of tyrosine kinases and other receptors. Recently it has been shown that this interaction is mediated by phosphorylation-independent interactions between a secondary binding site found exclusively on the N-SH2 domain and a region of the FGFR1 tyrosine kinase domain. This secondary site on the SH2 cooperates with the canonical pY site to regulate selectivity in mediating a specific cellular process. C-SH2 binds to an intramolecular site on PLCgamma itself which allows it to hydrolyze phosphatidylinositol-4,5-bisphosphate into diacylglycerol and inositol triphosphate. These then activate protein kinase C and release calcium. In general SH2 domains are involved in signal transduction. They typically bind pTyr-containing ligands via two surface pockets, a pTyr and hydrophobic binding pocket, allowing proteins with SH2 domains to localize to tyrosine phosphorylated sites.


Pssm-ID: 199829  Cd Length: 99  Bit Score: 56.21  E-value: 9.93e-10
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 32455248 332 EWYWGDIS--REEVNEKLRDTA---DGTFLVRDaSTKMHGDYTLTLRKGGNNKLIKIFHRDG----KYGFSDPLTFSSVV 402
Cdd:cd10341   5 PWFHGKLGdgRDEAEKLLLEYCeggDGTFLVRE-SETFVGDYTLSFWRNGKVQHCRIRSRQEngekKYYLTDNLVFDSLY 83
                        90
                ....*....|.
gi 32455248 403 ELINHYRNESL 413
Cdd:cd10341  84 ELIDYYRQNPL 94
SH2_CRK_like cd09926
Src homology 2 domain found in cancer-related signaling adaptor protein CRK; SH2 domain in the ...
333-373 1.43e-09

Src homology 2 domain found in cancer-related signaling adaptor protein CRK; SH2 domain in the CRK proteins. CRKI (SH2-SH3) and CRKII (SH2-SH3-SH3) are splicing isoforms of the oncoprotein CRK. CRKs regulate transcription and cytoskeletal reorganization for cell growth and motility by linking tyrosine kinases to small G proteins. The SH2 domain of CRK associates with tyrosine-phosphorylated receptors or components of focal adhesions, such as p130Cas and paxillin. CRK transmits signals to small G proteins through effectors that bind its SH3 domain, such as C3G, the guanine-nucleotide exchange factor (GEF) for Rap1 and R-Ras, and DOCK180, the GEF for Rac6. The binding of p130Cas to the CRK-C3G complex activates Rap1, leading to regulation of cell adhesion, and activates R-Ras, leading to JNK-mediated activation of cell proliferation, whereas the binding of CRK DOCK180 induces Rac1-mediated activation of cellular migration. The activity of the different splicing isoforms varies greatly with CRKI displaying substantial transforming activity, CRKII less so, and phosphorylated CRKII with no biological activity whatsoever. CRKII has a linker region with a phosphorylated Tyr and an additional C-terminal SH3 domain. The phosphorylated Tyr creates a binding site for its SH2 domain which disrupts the association between CRK and its SH2 target proteins. In general SH2 domains are involved in signal transduction. They typically bind pTyr-containing ligands via two surface pockets, a pTyr and hydrophobic binding pocket, allowing proteins with SH2 domains to localize to tyrosine phosphorylated sites.


Pssm-ID: 198180 [Multi-domain]  Cd Length: 106  Bit Score: 55.94  E-value: 1.43e-09
                        10        20        30        40
                ....*....|....*....|....*....|....*....|.
gi 32455248 333 WYWGDISREEVNEKLRDTADGTFLVRDASTkMHGDYTLTLR 373
Cdd:cd09926   9 WYFGPMSRQEAQELLQGQRHGVFLVRDSST-IPGDYVLSVS 48
SH2_Src_Src42 cd10370
Src homology 2 (SH2) domain found in the Src oncogene at 42A (Src42); Src42 is a member of the ...
333-412 1.59e-09

Src homology 2 (SH2) domain found in the Src oncogene at 42A (Src42); Src42 is a member of the Src non-receptor type tyrosine kinase family of proteins. The integration of receptor tyrosine kinase-induced RAS and Src42 signals by Connector eNhancer of KSR (CNK) as a two-component input is essential for RAF activation in Drosophila. Src42 is present in a wide variety of organisms including: California sea hare, pea aphid, yellow fever mosquito, honey bee, Panamanian leafcutter ant, and sea urchin. Src42 has a unique N-terminal domain, an SH3 domain, an SH2 domain, a kinase domain and a regulatory tail, as do the other members of the family. Like the other members of the Src family the SH2 domain in addition to binding the target, also plays an autoinhibitory role by binding to its C-terminal tail. In general SH2 domains are involved in signal transduction. They typically bind pTyr-containing ligands via two surface pockets, a pTyr and hydrophobic binding pocket, allowing proteins with SH2 domains to localize to tyrosine phosphorylated sites.


Pssm-ID: 198233  Cd Length: 96  Bit Score: 55.59  E-value: 1.59e-09
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 32455248 333 WYWGDISREEVNEKLRDTAD--GTFLVRDASTKmHGDYTLTLRKGGNNKLIKIFHRD-GKYGFSDPLTFSSVVELINHYR 409
Cdd:cd10370   5 WYFGKIKRIEAEKKLLLPENehGAFLIRDSESR-HNDYSLSVRDGDTVKHYRIRQLDeGGFFIARRTTFRTLQELVEHYS 83

                ...
gi 32455248 410 NES 412
Cdd:cd10370  84 KDS 86
SH2_C-SH2_SHP_like cd09931
C-terminal Src homology 2 (C-SH2) domain found in SH2 domain Phosphatases (SHP) proteins; The ...
333-409 1.99e-09

C-terminal Src homology 2 (C-SH2) domain found in SH2 domain Phosphatases (SHP) proteins; The SH2 domain phosphatases (SHP-1, SHP-2/Syp, Drosophila corkscrew (csw), and Caenorhabditis elegans Protein Tyrosine Phosphatase (Ptp-2)) are cytoplasmic signaling enzymes. They are both targeted and regulated by interactions of their SH2 domains with phosphotyrosine docking sites. These proteins contain two SH2 domains (N-SH2, C-SH2) followed by a tyrosine phosphatase (PTP) domain, and a C-terminal extension. Shp1 and Shp2 have two tyrosyl phosphorylation sites in their C-tails, which are phosphorylated differentially by receptor and nonreceptor PTKs. Csw retains the proximal tyrosine and Ptp-2 lacks both sites. Shp-binding proteins include receptors, scaffolding adapters, and inhibitory receptors. Some of these bind both Shp1 and Shp2 while others bind only one. Most proteins that bind a Shp SH2 domain contain one or more immuno-receptor tyrosine-based inhibitory motifs (ITIMs): [SIVL]xpYxx[IVL]. Shp1 N-SH2 domain blocks the catalytic domain and keeps the enzyme in the inactive conformation, and is thus believed to regulate the phosphatase activity of SHP-1. Its C-SH2 domain is thought to be involved in searching for phosphotyrosine activators. The SHP2 N-SH2 domain is a conformational switch; it either binds and inhibits the phosphatase, or it binds phosphoproteins and activates the enzyme. The C-SH2 domain contributes binding energy and specificity, but it does not have a direct role in activation. Csw SH2 domain function is essential, but either SH2 domain can fulfill this requirement. The role of the csw SH2 domains during Sevenless receptor tyrosine kinase (SEV) signaling is to bind Daughter of Sevenless rather than activated SEV. Ptp-2 acts in oocytes downstream of sheath/oocyte gap junctions to promote major sperm protein (MSP)-induced MAP Kinase (MPK-1) phosphorylation. Ptp-2 functions in the oocyte cytoplasm, not at the cell surface to inhibit multiple RasGAPs, resulting in sustained Ras activation. It is thought that MSP triggers PTP-2/Ras activation and ROS production to stimulate MPK-1 activity essential for oocyte maturation and that secreted MSP domains and Cu/Zn superoxide dismutases function antagonistically to control ROS and MAPK signaling. In general SH2 domains are involved in signal transduction. They typically bind pTyr-containing ligands via two surface pockets, a pTyr and hydrophobic binding pocket, allowing proteins with SH2 domains to localize to tyrosine phosphorylated sites.


Pssm-ID: 198185  Cd Length: 99  Bit Score: 55.36  E-value: 1.99e-09
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 32455248 333 WYWGDISREEVNEKLRDTA-DGTFLVRDASTKMhGDYTLTLRKGgNNKL--IKIFHRDGKYGFSDPLTFSSVVELINHYR 409
Cdd:cd09931   2 WFHGHLSGKEAEKLLLEKGkPGSFLVRESQSKP-GDFVLSVRTD-DDKVthIMIRCQGGKYDVGGGEEFDSLTDLVEHYK 79
SH2_Vav2 cd10406
Src homology 2 (SH2) domain found in the Vav2 proteins; Proto-oncogene vav is a member of the ...
624-717 2.35e-09

Src homology 2 (SH2) domain found in the Vav2 proteins; Proto-oncogene vav is a member of the Dbl family of guanine nucleotide exchange factors (GEF) for the Rho family of GTP binding proteins. All vavs are activated by tyrosine phosphorylation leading to their activation. There are three Vav mammalian family members: Vav1 which is expressed in the hematopoietic system, and Vav2 and Vav3 are more ubiquitously expressed. Vav2 is a GEF for RhoA, RhoB and RhoG and may activate Rac1 and Cdc42. Vav2 has been shown to interact with CD19 and Grb2. Alternatively spliced transcript variants encoding different isoforms have been found for Vav2. Vav proteins are involved in several processes that require cytoskeletal reorganization, such as the formation of the immunological synapse (IS), phagocytosis, platelet aggregation, spreading, and transformation. Vavs function as guanine nucleotide exchange factors (GEFs) for the Rho/Rac family of GTPases. Vav family members have several conserved motifs/domains including: a leucine-rich region, a leucine-zipper, a calponin homology (CH) domain, an acidic domain, a Dbl-homology (DH) domain, a pleckstrin homology (PH) domain, a cysteine-rich domain, 2 SH3 domains, a proline-rich region, and a SH2 domain. Vavs are the only known Rho GEFs that have both the DH/PH motifs and SH2/SH3 domains in the same protein. The leucine-rich helix-loop-helix (HLH) domain is thought to be involved in protein heterodimerization with other HLH proteins and it may function as a negative regulator by forming inactive heterodimers. The CH domain is usually involved in the association with filamentous actin, but in Vav it controls NFAT stimulation, Ca2+ mobilization, and its transforming activity. Acidic domains are involved in protein-protein interactions and contain regulatory tyrosines. The DH domain is a GDP-GTP exchange factor on Rho/Rac GTPases. The PH domain in involved in interactions with GTP-binding proteins, lipids and/or phosphorylated serine/threonine residues. The SH3 domain is involved in localization of proteins to specific sites within the cell interacting with protein with proline-rich sequences. The SH2 domain mediates a high affinity interaction with tyrosine phosphorylated proteins. In general SH2 domains are involved in signal transduction. They typically bind pTyr-containing ligands via two surface pockets, a pTyr and hydrophobic binding pocket, allowing proteins with SH2 domains to localize to tyrosine phosphorylated sites.


Pssm-ID: 198269  Cd Length: 103  Bit Score: 55.07  E-value: 2.35e-09
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 32455248 624 WNVGSSNRNKAENLLRGKRDGTFLVRESSKQG-CYACSVVVDGEVKHCVINKTATGYGFAEPYNlYSSLKELVLHYQHTS 702
Cdd:cd10406   7 WFAGNMERQQTDNLLKSHASGTYLIRERPAEAeRFAISIKFNDEVKHIKVVEKDNWIHITEAKK-FESLLELVEYYQCHS 85
                        90
                ....*....|....*
gi 32455248 703 LVQHNDSLNVTLAYP 717
Cdd:cd10406  86 LKESFKQLDTTLKYP 100
SH2_Vav1 cd10405
Src homology 2 (SH2) domain found in the Vav1 proteins; Proto-oncogene vav is a member of the ...
615-717 2.39e-09

Src homology 2 (SH2) domain found in the Vav1 proteins; Proto-oncogene vav is a member of the Dbl family of guanine nucleotide exchange factors (GEF) for the Rho family of GTP binding proteins. All vavs are activated by tyrosine phosphorylation leading to their activation. There are three Vav mammalian family members: Vav1 which is expressed in the hematopoietic system, and Vav2 and Vav3 are more ubiquitously expressed. Vav1 plays a role in T-cell and B-cell development and activation. It has been identified as the specific binding partner of Nef proteins from HIV-1, resulting in morphological changes, cytoskeletal rearrangements, and the JNK/SAPK signaling cascade, leading to increased levels of viral transcription and replication. Vav1 has been shown to interact with Ku70, PLCG1, Lymphocyte cytosolic protein 2, Janus kinase 2, SIAH2, S100B, Abl gene, ARHGDIB, SHB, PIK3R1, PRKCQ, Grb2, MAPK1, Syk, Linker of activated T cells, Cbl gene and EZH2. Vav proteins are involved in several processes that require cytoskeletal reorganization, such as the formation of the immunological synapse (IS), phagocytosis, platelet aggregation, spreading, and transformation. Vavs function as guanine nucleotide exchange factors (GEFs) for the Rho/Rac family of GTPases. Vav family members have several conserved motifs/domains including: a leucine-rich region, a leucine-zipper, a calponin homology (CH) domain, an acidic domain, a Dbl-homology (DH) domain, a pleckstrin homology (PH) domain, a cysteine-rich domain, 2 SH3 domains, a proline-rich region, and a SH2 domain. Vavs are the only known Rho GEFs that have both the DH/PH motifs and SH2/SH3 domains in the same protein. The leucine-rich helix-loop-helix (HLH) domain is thought to be involved in protein heterodimerization with other HLH proteins and it may function as a negative regulator by forming inactive heterodimers. The CH domain is usually involved in the association with filamentous actin, but in Vav it controls NFAT stimulation, Ca2+ mobilization, and its transforming activity. Acidic domains are involved in protein-protein interactions and contain regulatory tyrosines. The DH domain is a GDP-GTP exchange factor on Rho/Rac GTPases. The PH domain in involved in interactions with GTP-binding proteins, lipids and/or phosphorylated serine/threonine residues. The SH3 domain is involved in localization of proteins to specific sites within the cell interacting with protein with proline-rich sequences. The SH2 domain mediates a high affinity interaction with tyrosine phosphorylated proteins. In general SH2 domains are involved in signal transduction. They typically bind pTyr-containing ligands via two surface pockets, a pTyr and hydrophobic binding pocket, allowing proteins with SH2 domains to localize to tyrosine phosphorylated sites.


Pssm-ID: 198268  Cd Length: 103  Bit Score: 55.02  E-value: 2.39e-09
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 32455248 615 DLPHHdekTWNVGSSNRNKAENLLRGKRDGTFLVRESSKQ-GCYACSVVVDGEVKHCVINKTATGYGFAEPyNLYSSLKE 693
Cdd:cd10405   1 DLSVH---LWYAGPMERAGAESILANRSDGTYLVRQRVKDaAEFAISIKYNVEVKHIKIMTAEGLYRITEK-KAFRGLTE 76
                        90       100
                ....*....|....*....|....
gi 32455248 694 LVLHYQHTSLVQHNDSLNVTLAYP 717
Cdd:cd10405  77 LVEFYQQNSLKDCFKSLDTTLQFP 100
SH2_Src_family cd09933
Src homology 2 (SH2) domain found in the Src family of non-receptor tyrosine kinases; The Src ...
624-717 2.88e-09

Src homology 2 (SH2) domain found in the Src family of non-receptor tyrosine kinases; The Src family kinases are nonreceptor tyrosine kinases that have been implicated in pathways regulating proliferation, angiogenesis, invasion and metastasis, and bone metabolism. It is thought that transforming ability of Src is linked to its ability to activate key signaling molecules in these pathways, rather than through direct activity. As such blocking Src activation has been a target for drug companies. Src family members can be divided into 3 groups based on their expression pattern: 1) Src, Fyn, and Yes; 2) Blk, Fgr, Hck, Lck, and Lyn; and 3) Frk-related kinases Frk/Rak and Iyk/Bsk Of these, cellular c-Src is the best studied and most frequently implicated in oncogenesis. The c-Src contains five distinct regions: a unique N-terminal domain, an SH3 domain, an SH2 domain, a kinase domain and a regulatory tail, as do the other members of the family. Src exists in both active and inactive conformations. Negative regulation occurs through phosphorylation of Tyr, resulting in an intramolecular association between phosphorylated Tyr and the SH2 domain of SRC, which locks the protein in a closed conformation. Further stabilization of the inactive state occurs through interactions between the SH3 domain and a proline-rich stretch of residues within the kinase domain. Conversely, dephosphorylation of Tyr allows SRC to assume an open conformation. Full activity requires additional autophosphorylation of a Tyr residue within the catalytic domain. Loss of the negative-regulatory C-terminal segment has been shown to result in increased activity and transforming potential. Phosphorylation of the C-terminal Tyr residue by C-terminal Src kinase (Csk) and Csk homology kinase results in increased intramolecular interactions and consequent Src inactivation. Specific phosphatases, protein tyrosine phosphatase a (PTPa) and the SH-containing phosphatases SHP1/SHP2, have also been shown to take a part in Src activation. Src is also activated by direct binding of focal adhesion kinase (Fak) and Crk-associated substrate (Cas) to the SH2 domain. SRC activity can also be regulated by numerous receptor tyrosine kinases (RTKs), such as Her2, epidermal growth factor receptor (EGFR), fibroblast growth factor receptor, platelet-derived growth factor receptor (PDGFR), and vascular endothelial growth factor receptor (VEGFR). In general SH2 domains are involved in signal transduction. They typically bind pTyr-containing ligands via two surface pockets, a pTyr and hydrophobic binding pocket, allowing proteins with SH2 domains to localize to tyrosine phosphorylated sites.


Pssm-ID: 199827  Cd Length: 101  Bit Score: 54.90  E-value: 2.88e-09
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 32455248 624 WNVGSSNRNKAENLL---RGKRdGTFLVRES-SKQGCYACSVVvDGE------VKHCVINKTATGYGFAEPYNLYSSLKE 693
Cdd:cd09933   5 WFFGKIKRKDAEKLLlapGNPR-GTFLIRESeTTPGAYSLSVR-DGDdargdtVKHYRIRKLDNGGYYITTRATFPTLQE 82
                        90       100
                ....*....|....*....|....
gi 32455248 694 LVLHYQhtslvQHNDSLNVTLAYP 717
Cdd:cd09933  83 LVQHYS-----KDADGLCCRLTVP 101
SH2_Fps_family cd10361
Src homology 2 (SH2) domain found in feline sarcoma, Fujinami poultry sarcoma, and fes-related ...
326-408 3.49e-09

Src homology 2 (SH2) domain found in feline sarcoma, Fujinami poultry sarcoma, and fes-related (Fes/Fps/Fer) proteins; The Fps family consists of members Fps/Fes and Fer/Flk/Tyk3. They are cytoplasmic protein-tyrosine kinases implicated in signaling downstream from cytokines, growth factors and immune receptors. Fes/Fps/Fer contains three coiled-coil regions, an SH2 (Src-homology-2) and a TK (tyrosine kinase catalytic) domain signature. Members here include: Fps/Fes, Fer, Kin-31, and In general SH2 domains are involved in signal transduction. They typically bind pTyr-containing ligands via two surface pockets, a pTyr and hydrophobic binding pocket, allowing proteins with SH2 domains to localize to tyrosine phosphorylated sites.


Pssm-ID: 198224  Cd Length: 90  Bit Score: 54.07  E-value: 3.49e-09
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 32455248 326 MSLQDAEWYWGDISREEVNEKLRDtaDGTFLVRDASTKMHG--DYTLTLRKGGNNKLIkIFHRD--GKYGFsDPLTFSSV 401
Cdd:cd10361   1 KDLENEPYYHGLLPREDAEELLKN--DGDFLVRKTEPKGGGkrKLVLSVRWDGKIRHF-VINRDdgGKYYI-EGKSFKSI 76

                ....*..
gi 32455248 402 VELINHY 408
Cdd:cd10361  77 SELINYY 83
SH2_Tec_Bmx cd10399
Src homology 2 (SH2) domain found in Tec protein, Bmx; A member of the Tec protein tyrosine ...
620-702 3.63e-09

Src homology 2 (SH2) domain found in Tec protein, Bmx; A member of the Tec protein tyrosine kinase Bmx is expressed in the endothelium of large arteries, fetal endocardium, adult endocardium of the left ventricle, bone marrow, lung, testis, granulocytes, myeloid cell lines, and prostate cell lines. Bmx is involved in the regulation of Rho and serum response factor (SRF). Bmx has been shown to interact with PAK1, PTK2, PTPN21, and RUFY1. Most of the Tec family members have a PH domain (Txk and the short (type 1) splice variant of Drosophila Btk29A are exceptions), a Tec homology (TH) domain, a SH3 domain, a SH2 domain, and a protein kinase catalytic domain. The TH domain consists of a Zn2+-binding Btk motif and a proline-rich region. The Btk motif is found in Tec kinases, Ras GAP, and IGBP. It is crucial for the function of Tec PH domains. It is not present in Txk and the type 1 splice form of the Drosophila homolog. The proline-rich regions are highly conserved for the most part with the exception of Bmx whose residues surrounding the PXXP motif are not conserved (TH-like) and Btk29A which is entirely unique with large numbers of glycine residues (TH-extended). Tec family members all lack a C-terminal tyrosine having an autoinhibitory function in its phosphorylated state. In general SH2 domains are involved in signal transduction. They typically bind pTyr-containing ligands via two surface pockets, a pTyr and hydrophobic binding pocket, allowing proteins with SH2 domains to localize to tyrosine phosphorylated sites.


Pssm-ID: 198262  Cd Length: 106  Bit Score: 54.58  E-value: 3.63e-09
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 32455248 620 DEKTWNVGSSNRNKAENLLRGK-RDGTFLVRESSKQGCYACSVVV------DGEVKHCVINKTATG-YGFAEPYnLYSSL 691
Cdd:cd10399   4 DAYDWFAGNISRSQSEQLLRQKgKEGAFMVRNSSQVGMYTVSLFSkavndkKGTVKHYHVHTNAENkLYLAENY-CFDSI 82
                        90
                ....*....|.
gi 32455248 692 KELVLHYQHTS 702
Cdd:cd10399  83 PKLIHYHQHNS 93
SH2_Tec_Btk cd10397
Src homology 2 (SH2) domain found in Tec protein, Bruton's tyrosine kinase (Btk); A member of ...
624-718 4.75e-09

Src homology 2 (SH2) domain found in Tec protein, Bruton's tyrosine kinase (Btk); A member of the Tec protein tyrosine kinase Btk is expressed in bone marrow, spleen, all hematopoietic cells except T lymphocytes and plasma cells where it plays a crucial role in B cell maturation and mast cell activation. Btk has been shown to interact with GNAQ, PLCG2, protein kinase D1, B-cell linker, SH3BP5, caveolin 1, ARID3A, and GTF2I. Most of the Tec family members have a PH domain (Txk and the short (type 1) splice variant of Drosophila Btk29A are exceptions), a Tec homology (TH) domain, a SH3 domain, a SH2 domain, and a protein kinase catalytic domain. Btk is implicated in the primary immunodeficiency disease X-linked agammaglobulinemia (Bruton's agammaglobulinemia). The TH domain consists of a Zn2+-binding Btk motif and a proline-rich region. The Btk motif is found in Tec kinases, Ras GAP, and IGBP. It is crucial for the function of Tec PH domains and it's lack of presence in Txk is not surprising since it lacks a PH domain. The type 1 splice form of the Drosophila homolog also lacks both the PH domain and the Btk motif. The proline-rich regions are highly conserved for the most part with the exception of Bmx whose residues surrounding the PXXP motif are not conserved (TH-like) and Btk29A which is entirely unique with large numbers of glycine residues (TH-extended). Tec family members all lack a C-terminal tyrosine having an autoinhibitory function in its phosphorylated state. Two tyrosine phosphorylation (pY) sites have been identified in Btk: one located in the activation loop of the catalytic domain which regulates the transition between open (active) and closed (inactive) states and the other in its SH3 domain. In general SH2 domains are involved in signal transduction. They typically bind pTyr-containing ligands via two surface pockets, a pTyr and hydrophobic binding pocket, allowing proteins with SH2 domains to localize to tyrosine phosphorylated sites.


Pssm-ID: 198260 [Multi-domain]  Cd Length: 106  Bit Score: 54.46  E-value: 4.75e-09
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 32455248 624 WNVGSSNRNKAENLLRGK-RDGTFLVRESSKQGCYACSVVV------DGEVKHCVINKTATGYGFAEPYNLYSSLKELVL 696
Cdd:cd10397   8 WYSKNMTRSQAEQLLKQEgKEGGFIVRDSSKAGKYTVSVFAksagdpQGVIRHYVVCSTPQSQYYLAEKHLFSTIPELIN 87
                        90       100
                ....*....|....*....|..
gi 32455248 697 HYQHTSLvqhndSLNVTLAYPV 718
Cdd:cd10397  88 YHQHNAA-----GLISRLKYPV 104
SH3 smart00326
Src homology 3 domains; Src homology 3 (SH3) domains bind to target proteins through sequences ...
4-75 4.83e-09

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: 52.54  E-value: 4.83e-09
                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|..
gi 32455248      4 EGYQYRALYDYKKEREEDIDLHLGDILTVnkgslvaLGFSDGqearpeeiGWLNGYNEtTGERGDFPGTYVE 75
Cdd:smart00326   1 EGPQVRALYDYTAQDPDELSFKKGDIITV-------LEKSDD--------GWWKGRLG-RGKEGLFPSNYVE 56
SH2_C-SH2_SHP_like cd09931
C-terminal Src homology 2 (C-SH2) domain found in SH2 domain Phosphatases (SHP) proteins; The ...
624-720 5.21e-09

C-terminal Src homology 2 (C-SH2) domain found in SH2 domain Phosphatases (SHP) proteins; The SH2 domain phosphatases (SHP-1, SHP-2/Syp, Drosophila corkscrew (csw), and Caenorhabditis elegans Protein Tyrosine Phosphatase (Ptp-2)) are cytoplasmic signaling enzymes. They are both targeted and regulated by interactions of their SH2 domains with phosphotyrosine docking sites. These proteins contain two SH2 domains (N-SH2, C-SH2) followed by a tyrosine phosphatase (PTP) domain, and a C-terminal extension. Shp1 and Shp2 have two tyrosyl phosphorylation sites in their C-tails, which are phosphorylated differentially by receptor and nonreceptor PTKs. Csw retains the proximal tyrosine and Ptp-2 lacks both sites. Shp-binding proteins include receptors, scaffolding adapters, and inhibitory receptors. Some of these bind both Shp1 and Shp2 while others bind only one. Most proteins that bind a Shp SH2 domain contain one or more immuno-receptor tyrosine-based inhibitory motifs (ITIMs): [SIVL]xpYxx[IVL]. Shp1 N-SH2 domain blocks the catalytic domain and keeps the enzyme in the inactive conformation, and is thus believed to regulate the phosphatase activity of SHP-1. Its C-SH2 domain is thought to be involved in searching for phosphotyrosine activators. The SHP2 N-SH2 domain is a conformational switch; it either binds and inhibits the phosphatase, or it binds phosphoproteins and activates the enzyme. The C-SH2 domain contributes binding energy and specificity, but it does not have a direct role in activation. Csw SH2 domain function is essential, but either SH2 domain can fulfill this requirement. The role of the csw SH2 domains during Sevenless receptor tyrosine kinase (SEV) signaling is to bind Daughter of Sevenless rather than activated SEV. Ptp-2 acts in oocytes downstream of sheath/oocyte gap junctions to promote major sperm protein (MSP)-induced MAP Kinase (MPK-1) phosphorylation. Ptp-2 functions in the oocyte cytoplasm, not at the cell surface to inhibit multiple RasGAPs, resulting in sustained Ras activation. It is thought that MSP triggers PTP-2/Ras activation and ROS production to stimulate MPK-1 activity essential for oocyte maturation and that secreted MSP domains and Cu/Zn superoxide dismutases function antagonistically to control ROS and MAPK signaling. In general SH2 domains are involved in signal transduction. They typically bind pTyr-containing ligands via two surface pockets, a pTyr and hydrophobic binding pocket, allowing proteins with SH2 domains to localize to tyrosine phosphorylated sites.


Pssm-ID: 198185  Cd Length: 99  Bit Score: 54.21  E-value: 5.21e-09
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 32455248 624 WNVGSSNRNKAENLLRGK-RDGTFLVRES-SKQGCYACSVVV-DGEVKHCVINKTATGYGFAePYNLYSSLKELVLHYQH 700
Cdd:cd09931   2 WFHGHLSGKEAEKLLLEKgKPGSFLVRESqSKPGDFVLSVRTdDDKVTHIMIRCQGGKYDVG-GGEEFDSLTDLVEHYKK 80
                        90       100
                ....*....|....*....|
gi 32455248 701 TSLVQHNDSLnVTLAYPVYA 720
Cdd:cd09931  81 NPMVETSGTV-VHLKQPLNA 99
SH2_Tec_Txk cd10398
Src homology 2 (SH2) domain found in Tec protein, Txk; A member of the Tec protein tyrosine ...
624-718 6.30e-09

Src homology 2 (SH2) domain found in Tec protein, Txk; A member of the Tec protein tyrosine kinase Txk is expressed in thymus, spleen, lymph node, T lymphocytes, NK cells, mast cell lines, and myeloid cell line. Txk plays a role in TCR signal transduction, T cell development, and selection which is analogous to the function of Itk. Txk has been shown to interact with IFN-gamma. Unlike most of the Tec family members Txk lacks a PH domain. Instead Txk has a unique region containing a palmitoylated cysteine string which has a similar membrane tethering function as the PH domain. Txk also has a zinc-binding motif, a SH3 domain, a SH2 domain, and a protein kinase catalytic domain. The TH domain consists of a Zn2+-binding Btk motif and a proline-rich region. The Btk motif is found in Tec kinases, Ras GAP, and IGBP and crucial to the function of the PH domain. It is not present in Txk which is not surprising since it lacks a PH domain. The type 1 splice form of the Drosophila homolog also lacks both the PH domain and the Btk motif. The proline-rich regions are highly conserved for the most part with the exception of Bmx whose residues surrounding the PXXP motif are not conserved (TH-like) and Btk29A which is entirely unique with large numbers of glycine residues (TH-extended). Tec family members all lack a C-terminal tyrosine having an autoinhibitory function in its phosphorylated state. In general SH2 domains are involved in signal transduction. They typically bind pTyr-containing ligands via two surface pockets, a pTyr and hydrophobic binding pocket, allowing proteins with SH2 domains to localize to tyrosine phosphorylated sites.


Pssm-ID: 198261  Cd Length: 106  Bit Score: 54.18  E-value: 6.30e-09
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 32455248 624 WNVGSSNRNKAENLLRGK-RDGTFLVRESSKQGCYACSVVV------DGEVKHCVINKTATGYGFAEPYNLYSSLKELVL 696
Cdd:cd10398   8 WYHKNITRNQAERLLRQEsKEGAFIVRDSRHLGSYTISVFTrarrstEASIKHYQIKKNDSGQWYVAERHLFQSIPELIQ 87
                        90       100
                ....*....|....*....|..
gi 32455248 697 HYQHTSLvqhndSLNVTLAYPV 718
Cdd:cd10398  88 YHQHNAA-----GLMSRLRYPV 104
SH2_SOCS1 cd10382
Src homology 2 (SH2) domain found in suppressor of cytokine signaling (SOCS) proteins; SH2 ...
328-408 6.81e-09

Src homology 2 (SH2) domain found in suppressor of cytokine signaling (SOCS) proteins; SH2 domain found in SOCS proteins. SOCS was first recognized as a group of cytokine-inducible SH2 (CIS) domain proteins comprising eight family members in human (CIS and SOCS1-SOCS7). In addition to the SH2 domain, SOCS proteins have a variable N-terminal domain and a conserved SOCS box in the C-terminal domain. SOCS proteins bind to a substrate via their SH2 domain. The prototypical members, CIS and SOCS1-SOCS3, have been shown to regulate growth hormone signaling in vitro and in a classic negative feedback response compete for binding at phosphotyrosine sites in JAK kinase and receptor pathways to displace effector proteins and target bound receptors for proteasomal degradation. Loss of SOCS activity results in excessive cytokine signaling associated with a variety of hematopoietic, autoimmune, and inflammatory diseases and certain cancers. Members (SOCS4-SOCS7) were identified by their conserved SOCS box, an adapter motif of 3 helices that associates substrate binding domains, such as the SOCS SH2 domain, ankryin, and WD40 with ubiquitin ligase components. These show limited cytokine induction. In general SH2 domains are involved in signal transduction. They typically bind pTyr-containing ligands via two surface pockets, a pTyr and hydrophobic binding pocket, allowing proteins with SH2 domains to localize to tyrosine phosphorylated sites.


Pssm-ID: 198245  Cd Length: 98  Bit Score: 53.52  E-value: 6.81e-09
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 32455248 328 LQDAEWYWGDISREEVNEKLRDTADGTFLVRDASTKMHGdYTLTLRKGGNNKLIKIFHRDGKYGFSD-PLTFSSVVELIN 406
Cdd:cd10382   7 LDASGFYWGPLSVEEAHAKLKREPVGTFLIRDSRQKNCF-FALSVKMASGPVSIRILFKAGKFSLDGsKESFDCLFKLLE 85

                ..
gi 32455248 407 HY 408
Cdd:cd10382  86 HY 87
SH2_Vav3 cd10407
Src homology 2 (SH2) domain found in the Vav3 proteins; Proto-oncogene vav is a member of the ...
624-717 8.53e-09

Src homology 2 (SH2) domain found in the Vav3 proteins; Proto-oncogene vav is a member of the Dbl family of guanine nucleotide exchange factors (GEF) for the Rho family of GTP binding proteins. All vavs are activated by tyrosine phosphorylation leading to their activation. There are three Vav mammalian family members: Vav1 which is expressed in the hematopoietic system, and Vav2 and Vav3 are more ubiquitously expressed. Vav3 preferentially activates RhoA, RhoG and, to a lesser extent, Rac1. Alternatively spliced transcript variants encoding different isoforms have been described for this gene. VAV3 has been shown to interact with Grb2. Vav proteins are involved in several processes that require cytoskeletal reorganization, such as the formation of the immunological synapse (IS), phagocytosis, platelet aggregation, spreading, and transformation. Vavs function as guanine nucleotide exchange factors (GEFs) for the Rho/Rac family of GTPases. Vav family members have several conserved motifs/domains including: a leucine-rich region, a leucine-zipper, a calponin homology (CH) domain, an acidic domain, a Dbl-homology (DH) domain, a pleckstrin homology (PH) domain, a cysteine-rich domain, 2 SH3 domains, a proline-rich region, and a SH2 domain. Vavs are the only known Rho GEFs that have both the DH/PH motifs and SH2/SH3 domains in the same protein. The leucine-rich helix-loop-helix (HLH) domain is thought to be involved in protein heterodimerization with other HLH proteins and it may function as a negative regulator by forming inactive heterodimers. The CH domain is usually involved in the association with filamentous actin, but in Vav it controls NFAT stimulation, Ca2+ mobilization, and its transforming activity. Acidic domains are involved in protein-protein interactions and contain regulatory tyrosines. The DH domain is a GDP-GTP exchange factor on Rho/Rac GTPases. The PH domain in involved in interactions with GTP-binding proteins, lipids and/or phosphorylated serine/threonine residues. The SH3 domain is involved in localization of proteins to specific sites within the cell interacting with protein with proline-rich sequences. The SH2 domain mediates a high affinity interaction with tyrosine phosphorylated proteins. In general SH2 domains are involved in signal transduction. They typically bind pTyr-containing ligands via two surface pockets, a pTyr and hydrophobic binding pocket, allowing proteins with SH2 domains to localize to tyrosine phosphorylated sites.


Pssm-ID: 198270  Cd Length: 103  Bit Score: 53.47  E-value: 8.53e-09
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 32455248 624 WNVGSSNRNKAENLLRGKRDGTFLVRESSKQ-GCYACSVVVDGEVKHCVInKTATGYGFAEPYNLYSSLKELVLHYQHTS 702
Cdd:cd10407   7 WYAGAMERLQAETELINRVNSTYLVRHRTKEsGEYAISIKYNNEVKHIKI-LTRDGFFHIAENRKFKSLMELVEYYKHHS 85
                        90
                ....*....|....*
gi 32455248 703 LVQHNDSLNVTLAYP 717
Cdd:cd10407  86 LKEGFRSLDTTLQFP 100
SH2_ABL cd09935
Src homology 2 (SH2) domain found in Abelson murine lymphosarcoma virus (ABL) proteins; ...
333-409 1.15e-08

Src homology 2 (SH2) domain found in Abelson murine lymphosarcoma virus (ABL) proteins; ABL-family proteins are highly conserved tyrosine kinases. Each ABL protein contains an SH3-SH2-TK (Src homology 3-Src homology 2-tyrosine kinase) domain cassette, which confers autoregulated kinase activity and is common among nonreceptor tyrosine kinases. Several types of posttranslational modifications control ABL catalytic activity, subcellular localization, and stability, with consequences for both cytoplasmic and nuclear ABL functions. Binding partners provide additional regulation of ABL catalytic activity, substrate specificity, and downstream signaling. By combining this cassette with actin-binding and -bundling domain, ABL proteins are capable of connecting phosphoregulation with actin-filament reorganization. Vertebrate paralogs, ABL1 and ABL2, have evolved to perform specialized functions. ABL1 includes nuclear localization signals and a DNA binding domain which is used to mediate DNA damage-repair functions, while ABL2 has additional binding capacity for actin and for microtubules to enhance its cytoskeletal remodeling functions. SH2 is involved in several autoinhibitory mechanism that constrain the enzymatic activity of the ABL-family kinases. In one mechanism SH2 and SH3 cradle the kinase domain while a cap sequence stabilizes the inactive conformation resulting in a locked inactive state. Another involves phosphatidylinositol 4,5-bisphosphate (PIP2) which binds the SH2 domain through residues normally required for phosphotyrosine binding in the linker segment between the SH2 and kinase domains. The SH2 domain contributes to ABL catalytic activity and target site specificity. It is thought that the ABL catalytic site and SH2 pocket have coevolved to recognize the same sequences. Recent work now supports a hierarchical processivity model in which the substrate target site most compatible with ABL kinase domain preferences is phosphorylated with greatest efficiency. If this site is compatible with the ABL SH2 domain specificity, it will then reposition and dock in the SH2 pocket. This mechanism also explains how ABL kinases phosphorylates poor targets on the same substrate if they are properly positioned and how relatively poor substrate proteins might be recruited to ABL through a complex with strong substrates that can also dock with the SH2 pocket. In general SH2 domains are involved in signal transduction. They typically bind pTyr-containing ligands via two surface pockets, a pTyr and hydrophobic binding pocket, allowing proteins with SH2 domains to localize to tyrosine phosphorylated sites.


Pssm-ID: 198189  Cd Length: 94  Bit Score: 52.78  E-value: 1.15e-08
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 32455248 333 WYWGDISREEVNEKLRDTADGTFLVRDASTKMhGDYTLTLRKGGnnkliKIFH------RDGKYGFSDPLTFSSVVELIN 406
Cdd:cd09935   5 WYHGPISRNAAEYLLSSGINGSFLVRESESSP-GQYSISLRYDG-----RVYHyrisedSDGKVYVTQEHRFNTLAELVH 78

                ...
gi 32455248 407 HYR 409
Cdd:cd09935  79 HHS 81
RhoGAP_OCRL1 cd04380
RhoGAP_OCRL1: RhoGAP (GTPase-activator protein [GAP] for Rho-like small GTPases) domain ...
128-274 1.18e-08

RhoGAP_OCRL1: RhoGAP (GTPase-activator protein [GAP] for Rho-like small GTPases) domain present in OCRL1-like proteins. OCRL1 (oculocerebrorenal syndrome of Lowe 1)-like proteins contain two conserved domains: a central inositol polyphosphate 5-phosphatase domain and a C-terminal Rho GAP domain, this GAP domain lacks the catalytic residue and therefore maybe inactive. OCRL-like proteins are type II inositol polyphosphate 5-phosphatases that can hydrolyze lipid PI(4,5)P2 and PI(3,4,5)P3 and soluble Ins(1,4,5)P3 and Ins(1,3,4,5)P4, but their individual specificities vary. The functionality of the RhoGAP domain is still unclear. Small GTPases cluster into distinct families, and all act as molecular switches, active in their GTP-bound form but inactive when GDP-bound. The Rho family of GTPases activates effectors involved in a wide variety of developmental processes, including regulation of cytoskeleton formation, cell proliferation and the JNK signaling pathway. GTPases generally have a low intrinsic GTPase hydrolytic activity but there are family-specific groups of GAPs that enhance the rate of GTP hydrolysis by several orders of magnitude.


Pssm-ID: 239845  Cd Length: 220  Bit Score: 56.20  E-value: 1.18e-08
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 32455248 128 APPLLIKLVEAIEKKGLECSTLYRTQS--SSNLAELRQLLDC-DTPSVDLEMIDVHVLADAFKRYLLDLPNPVIPAAVYS 204
Cdd:cd04380  50 IPKEIWRLVDYLYTRGLAQEGLFEEPGlpSEPGELLAEIRDAlDTGSPFNSPGSAESVAEALLLFLESLPDPIIPYSLYE 129
                        90       100       110       120       130       140       150
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 32455248 205 EMIslapevQSSEEYIQLLKKLIRSpSIPHQYWLTLQYLLKHFFKLSQTSSKNLLNARVLSEIFSPMLFR 274
Cdd:cd04380 130 RLL------EAVANNEEDKRQVIRI-SLPPVHRNVFVYLCSFLRELLSESADRGLDENTLATIFGRVLLR 192
SH2_Vav2 cd10406
Src homology 2 (SH2) domain found in the Vav2 proteins; Proto-oncogene vav is a member of the ...
333-429 1.34e-08

Src homology 2 (SH2) domain found in the Vav2 proteins; Proto-oncogene vav is a member of the Dbl family of guanine nucleotide exchange factors (GEF) for the Rho family of GTP binding proteins. All vavs are activated by tyrosine phosphorylation leading to their activation. There are three Vav mammalian family members: Vav1 which is expressed in the hematopoietic system, and Vav2 and Vav3 are more ubiquitously expressed. Vav2 is a GEF for RhoA, RhoB and RhoG and may activate Rac1 and Cdc42. Vav2 has been shown to interact with CD19 and Grb2. Alternatively spliced transcript variants encoding different isoforms have been found for Vav2. Vav proteins are involved in several processes that require cytoskeletal reorganization, such as the formation of the immunological synapse (IS), phagocytosis, platelet aggregation, spreading, and transformation. Vavs function as guanine nucleotide exchange factors (GEFs) for the Rho/Rac family of GTPases. Vav family members have several conserved motifs/domains including: a leucine-rich region, a leucine-zipper, a calponin homology (CH) domain, an acidic domain, a Dbl-homology (DH) domain, a pleckstrin homology (PH) domain, a cysteine-rich domain, 2 SH3 domains, a proline-rich region, and a SH2 domain. Vavs are the only known Rho GEFs that have both the DH/PH motifs and SH2/SH3 domains in the same protein. The leucine-rich helix-loop-helix (HLH) domain is thought to be involved in protein heterodimerization with other HLH proteins and it may function as a negative regulator by forming inactive heterodimers. The CH domain is usually involved in the association with filamentous actin, but in Vav it controls NFAT stimulation, Ca2+ mobilization, and its transforming activity. Acidic domains are involved in protein-protein interactions and contain regulatory tyrosines. The DH domain is a GDP-GTP exchange factor on Rho/Rac GTPases. The PH domain in involved in interactions with GTP-binding proteins, lipids and/or phosphorylated serine/threonine residues. The SH3 domain is involved in localization of proteins to specific sites within the cell interacting with protein with proline-rich sequences. The SH2 domain mediates a high affinity interaction with tyrosine phosphorylated proteins. In general SH2 domains are involved in signal transduction. They typically bind pTyr-containing ligands via two surface pockets, a pTyr and hydrophobic binding pocket, allowing proteins with SH2 domains to localize to tyrosine phosphorylated sites.


Pssm-ID: 198269  Cd Length: 103  Bit Score: 53.15  E-value: 1.34e-08
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 32455248 333 WYWGDISREEVNEKLRDTADGTFLVRDASTKMHgDYTLTLRKGGNNKLIKIFHRDGKYGFSDPLTFSSVVELINHYRNES 412
Cdd:cd10406   7 WFAGNMERQQTDNLLKSHASGTYLIRERPAEAE-RFAISIKFNDEVKHIKVVEKDNWIHITEAKKFESLLELVEYYQCHS 85
                        90
                ....*....|....*..
gi 32455248 413 LAQYNPKLDVKLLYPVS 429
Cdd:cd10406  86 LKESFKQLDTTLKYPYK 102
SH2_Nterm_shark_like cd10347
N-terminal Src homology 2 (SH2) domain found in SH2 domains, ANK, and kinase domain (shark) ...
333-408 1.40e-08

N-terminal Src homology 2 (SH2) domain found in SH2 domains, ANK, and kinase domain (shark) proteins; These non-receptor protein-tyrosine kinases contain two SH2 domains, five ankyrin (ANK)-like repeats, and a potential tyrosine phosphorylation site in the carboxyl-terminal tail which resembles the phosphorylation site in members of the src family. Like, mammalian non-receptor protein-tyrosine kinases, ZAP-70 and syk proteins, they do not have SH3 domains. However, the presence of ANK makes these unique among protein-tyrosine kinases. Both tyrosine kinases and ANK repeats have been shown to transduce developmental signals, and SH2 domains are known to participate intimately in tyrosine kinase signaling. These tyrosine kinases are believed to be involved in epithelial cell polarity. The members of this family include the shark (SH2 domains, ANK, and kinase domain) gene in Drosophila and yellow fever mosquitos, as well as the hydra protein HTK16. Drosophila Shark is proposed to transduce intracellularly the Crumbs, a protein necessary for proper organization of ectodermal epithelia, intercellular signal. In general SH2 domains are involved in signal transduction. They typically bind pTyr-containing ligands via two surface pockets, a pTyr and hydrophobic binding pocket, allowing proteins with SH2 domains to localize to tyrosine phosphorylated sites.


Pssm-ID: 198210  Cd Length: 81  Bit Score: 52.38  E-value: 1.40e-08
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 32455248 333 WYWGDISREEVNEKL--RDTADGTFLVRDaSTKMHGDYTLTLRKGGNNKLIKIF-HRDGKYGFS-DPLTFSSVVELINHY 408
Cdd:cd10347   3 WYHGKISREVAEALLlrEGGRDGLFLVRE-STSAPGDYVLSLLAQGEVLHYQIRrHGEDAFFSDdGPLIFHGLDTLIEHY 81
SH2_Nck2 cd10409
Src homology 2 (SH2) domain found in Nck; Nck proteins are adaptors that modulate actin ...
332-409 1.88e-08

Src homology 2 (SH2) domain found in Nck; Nck proteins are adaptors that modulate actin cytoskeleton dynamics by linking proline-rich effector molecules to tyrosine kinases or phosphorylated signaling intermediates. There are two members known in this family: Nck1 (Nckalpha) and Nck2 (Nckbeta and Growth factor receptor-bound protein 4 (Grb4)). They are characterized by having 3 SH3 domains and a C-terminal SH2 domain. Nck1 and Nck2 have overlapping functions as determined by gene knockouts. Both bind receptor tyrosine kinases and other tyrosine-phosphorylated proteins through their SH2 domains. In addition they also bind distinct targets. Neuronal signaling proteins: EphrinB1, EphrinB2, and Disabled-1 (Dab-1) all bind to Nck-2 exclusively. And in the case of PDGFR, Tyr(P)751 binds to Nck1 while Tyr(P)1009 binds to Nck2. Nck1 and Nck2 have a role in the infection process of enteropathogenic Escherichia coli (EPEC). Their SH3 domains are involved in recruiting and activating the N-WASP/Arp2/3 complex inducing actin polymerization resulting in the production of pedestals, dynamic bacteria-presenting protrusions of the plasma membrane. A similar thing occurs in the vaccinia virus where motile plasma membrane projections are formed beneath the virus. Recently it has been shown that the SH2 domains of both Nck1 and Nck2 bind the G-protein coupled receptor kinase-interacting protein 1 (GIT1) in a phosphorylation-dependent manner. In general SH2 domains are involved in signal transduction. They typically bind pTyr-containing ligands via two surface pockets, a pTyr and hydrophobic binding pocket, allowing proteins with SH2 domains to localize to tyrosine phosphorylated sites.


Pssm-ID: 198272  Cd Length: 98  Bit Score: 52.35  E-value: 1.88e-08
                        10        20        30        40        50        60        70
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 32455248 332 EWYWGDISREEVNEKLRDTA-DGTFLVRDASTKmHGDYTLTLRKGGNNKLIKIFHRDGKYGFSDPlTFSSVVELINHYR 409
Cdd:cd10409   2 EWYYGNVTRHQAECALNERGvEGDFLIRDSESS-PSDFSVSLKAVGKNKHFKVQLVDNVYCIGQR-RFNSMDELVEHYK 78
RhoGAP_ARHGAP6 cd04376
RhoGAP_ARHGAP6: RhoGAP (GTPase-activator protein [GAP] for Rho-like small GTPases) domain of ...
134-295 2.10e-08

RhoGAP_ARHGAP6: RhoGAP (GTPase-activator protein [GAP] for Rho-like small GTPases) domain of ArhGAP6-like proteins. ArhGAP6 shows GAP activity towards RhoA, but not towards Cdc42 and Rac1. ArhGAP6 is often deleted in microphthalmia with linear skin defects syndrome (MLS); MLS is a severe X-linked developmental disorder. Small GTPases cluster into distinct families, and all act as molecular switches, active in their GTP-bound form but inactive when GDP-bound. The Rho family of GTPases activates effectors involved in a wide variety of developmental processes, including regulation of cytoskeleton formation, cell proliferation and the JNK signaling pathway. GTPases generally have a low intrinsic GTPase hydrolytic activity but there are family-specific groups of GAPs that enhance the rate of GTP hydrolysis by several orders of magnitude.


Pssm-ID: 239841  Cd Length: 206  Bit Score: 55.14  E-value: 2.10e-08
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 32455248 134 KLVEA----IEKKGLECSTLYRTQSSSN-LAELRQLLDCDTPSVDLEMIDVHVLADAFKRYLLDLPNPVIPAAVYSEMI- 207
Cdd:cd04376  11 RLVESccqhLEKHGLQTVGIFRVGSSKKrVRQLREEFDRGIDVVLDENHSVHDVAALLKEFFRDMPDPLLPRELYTAFIg 90
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 32455248 208 --SLAPEVQSseEYIQLLKKLIRSPSIPhqywlTLQYLLKHFFKLSQTS-----------SKNLLNARVLSEIFSPML-- 272
Cdd:cd04376  91 taLLEPDEQL--EALQLLIYLLPPCNCD-----TLHRLLKFLHTVAEHAadsidedgqevSGNKMTSLNLATIFGPNLlh 163
                       170       180       190
                ....*....|....*....|....*....|.
gi 32455248 273 --------FRFSAASSDNTENLIKVIEILIS 295
Cdd:cd04376 164 kqksgereFVQASLRIEESTAIINVVQTMID 194
RhoGAP_Graf cd04374
RhoGAP_Graf: GTPase-activator protein (GAP) domain for Rho-like GTPases found in GRAF (GTPase ...
134-295 3.60e-08

RhoGAP_Graf: GTPase-activator protein (GAP) domain for Rho-like GTPases found in GRAF (GTPase regulator associated with focal adhesion kinase); Graf is a multi-domain protein, containing SH3 and PH domains, that binds focal adhesion kinase and influences cytoskeletal changes mediated by Rho proteins. Graf exhibits GAP activity toward RhoA and Cdc42, but only weakly activates Rac1. Small GTPases cluster into distinct families, and all act as molecular switches, active in their GTP-bound form but inactive when GDP-bound. The Rho family of GTPases activates effectors involved in a wide variety of developmental processes, including regulation of cytoskeleton formation, cell proliferation and the JNK signaling pathway. GTPases generally have a low intrinsic GTPase hydrolytic activity but there are family-specific groups of GAPs that enhance the rate of GTP hydrolysis by several orders of magnitude.


Pssm-ID: 239839  Cd Length: 203  Bit Score: 54.32  E-value: 3.60e-08
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 32455248 134 KLVEAIEKKGLECSTLYRT-QSSSNLAELRQLL----DCDTPSVDLE--MIDVHVLADAFKRYLLDLPNPVIPAAVYSEM 206
Cdd:cd04374  34 KCIEAVETRGINEQGLYRVvGVNSKVQKLLSLGldpkTSTPGDVDLDnsEWEIKTITSALKTYLRNLPEPLMTYELHNDF 113
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 32455248 207 ISLApEVQSSEEYIQLLKKLIRSpsIPHQYWLTLQYLLKHFFKLSQTSSKNLLNARVLSEIFSPMLFRFS----AASSDn 282
Cdd:cd04374 114 INAA-KSENLESRVNAIHSLVHK--LPEKNREMLELLIKHLTNVSDHSKKNLMTVSNLGVVFGPTLLRPQeetvAAIMD- 189
                       170
                ....*....|....*..
gi 32455248 283 tenlIK----VIEILIS 295
Cdd:cd04374 190 ----IKfqniVVEILIE 202
SH2_SOCS3 cd10384
Src homology 2 (SH2) domain found in suppressor of cytokine signaling (SOCS) proteins; SH2 ...
328-408 3.96e-08

Src homology 2 (SH2) domain found in suppressor of cytokine signaling (SOCS) proteins; SH2 domain found in SOCS proteins. SOCS was first recognized as a group of cytokine-inducible SH2 (CIS) domain proteins comprising eight family members in human (CIS and SOCS1-SOCS7). In addition to the SH2 domain, SOCS proteins have a variable N-terminal domain and a conserved SOCS box in the C-terminal domain. SOCS proteins bind to a substrate via their SH2 domain. The prototypical members, CIS and SOCS1-SOCS3, have been shown to regulate growth hormone signaling in vitro and in a classic negative feedback response compete for binding at phosphotyrosine sites in JAK kinase and receptor pathways to displace effector proteins and target bound receptors for proteasomal degradation. Loss of SOCS activity results in excessive cytokine signaling associated with a variety of hematopoietic, autoimmune, and inflammatory diseases and certain cancers. Members (SOCS4-SOCS7) were identified by their conserved SOCS box, an adapter motif of 3 helices that associates substrate binding domains, such as the SOCS SH2 domain, ankryin, and WD40 with ubiquitin ligase components. These show limited cytokine induction. In general SH2 domains are involved in signal transduction. They typically bind pTyr-containing ligands via two surface pockets, a pTyr and hydrophobic binding pocket, allowing proteins with SH2 domains to localize to tyrosine phosphorylated sites.


Pssm-ID: 198247  Cd Length: 101  Bit Score: 51.66  E-value: 3.96e-08
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 32455248 328 LQDAEWYWGDISREEVNEKLRDTADGTFLVRDASTKMHGdYTLTLRKGGNNKLIKIfHRDGKYGF--SDPL------TFS 399
Cdd:cd10384   7 LQESGFYWSTVSGKEANLLLSAEPAGTFLIRDSSDQRHF-FTLSVKTESGTKNLRI-QCEGGSFSlqTDPRstqpvpRFD 84

                ....*....
gi 32455248 400 SVVELINHY 408
Cdd:cd10384  85 CVLKLVHHY 93
SH2_SHF cd10392
Src homology 2 domain found in SH2 domain-containing adapter protein F (SHF); SHF is thought ...
333-428 4.00e-08

Src homology 2 domain found in SH2 domain-containing adapter protein F (SHF); SHF is thought to play a role in PDGF-receptor signaling and regulation of apoptosis. SHF is mainly expressed in skeletal muscle, brain, liver, prostate, testis, ovary, small intestine, and colon. SHF contains four putative tyrosine phosphorylation sites and an SH2 domain. In general SH2 domains are involved in signal transduction. They typically bind pTyr-containing ligands via two surface pockets, a pTyr and hydrophobic binding pocket, allowing proteins with SH2 domains to localize to tyrosine phosphorylated sites.


Pssm-ID: 198255  Cd Length: 98  Bit Score: 51.61  E-value: 4.00e-08
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 32455248 333 WYWGDISREEVNEKLRDTADGTFLVRDASTKMHgDYTLTLRKGGNNKLIKIFH-RDGKY--GFSDPLtFSSVVELINHYR 409
Cdd:cd10392   3 WYHGAISRTDAENLLRLCKEASYLVRNSETSKN-DFSLSLKSSQGFMHMKLSRtKEHKYvlGQNSPP-FSSVPEIIHHYA 80
                        90
                ....*....|....*....
gi 32455248 410 NESLAQYNPKlDVKLLYPV 428
Cdd:cd10392  81 SRKLPIKGAE-HMSLLYPV 98
SH2_SHB_SHD_SHE_SHF_like cd09945
Src homology 2 domain found in SH2 domain-containing adapter proteins B, D, E, and F (SHB, SHD, ...
333-428 5.72e-08

Src homology 2 domain found in SH2 domain-containing adapter proteins B, D, E, and F (SHB, SHD, SHE, SHF); SHB, SHD, SHE, and SHF are SH2 domain-containing proteins that play various roles throughout the cell. SHB functions in generating signaling compounds in response to tyrosine kinase activation. SHB contains proline-rich motifs, a phosphotyrosine binding (PTB) domain, tyrosine phosphorylation sites, and a SH2 domain. SHB mediates certain aspects of platelet-derived growth factor (PDGF) receptor-, fibroblast growth factor (FGF) receptor-, neural growth factor (NGF) receptor TRKA-, T cell receptor-, interleukin-2 (IL-2) receptor- and focal adhesion kinase- (FAK) signaling. SRC-like FYN-Related Kinase FRK/RAK (also named BSK/IYK or GTK) and SHB regulate apoptosis, proliferation and differentiation. SHB promotes apoptosis and is also required for proper mitogenicity, spreading and tubular morphogenesis in endothelial cells. SHB also plays a role in preventing early cavitation of embryoid bodies and reduces differentiation to cells expressing albumin, amylase, insulin and glucagon. SHB is a multifunctional protein that has difference responses in different cells under various conditions. SHE is expressed in heart, lung, brain, and skeletal muscle, while expression of SHD is restricted to the brain. SHF is mainly expressed in skeletal muscle, brain, liver, prostate, testis, ovary, small intestine, and colon. SHD may be a physiological substrate of c-Abl and may function as an adapter protein in the central nervous system. It is also thought to be involved in apoptotic regulation. SHD contains five YXXP motifs, a substrate sequence preferred by Abl tyrosine kinases, in addition to a poly-proline rich region and a C-terminal SH2 domain. SHE contains two pTry protein binding domains, protein interaction domain (PID) and a SH2 domain, followed by a glycine-proline rich region, all of which are N-terminal to the phosphotyrosine binding (PTB) domain. SHF contains four putative tyrosine phosphorylation sites and an SH2 domain. In general SH2 domains are involved in signal transduction. They typically bind pTyr-containing ligands via two surface pockets, a pTyr and hydrophobic binding pocket, allowing proteins with SH2 domains to localize to tyrosine phosphorylated sites.


Pssm-ID: 198198  Cd Length: 98  Bit Score: 50.89  E-value: 5.72e-08
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 32455248 333 WYWGDISREEVNEKLRDTADGTFLVRDASTKmHGDYTLTLRKGGNNKLIKIFH-RDGKY---GFSDPltFSSVVELINHY 408
Cdd:cd09945   3 WYHGAITRIEAESLLRPCKEGSYLVRNSEST-KQDYSLSLKSAKGFMHMRIQRnETGQYilgQFSRP--FETIPEMIRHY 79
                        90       100
                ....*....|....*....|....*.
gi 32455248 409 RNEslaqynpKLDVK------LLYPV 428
Cdd:cd09945  80 CLN-------KLPVRgaehmcLLEPV 98
SH2_BLNK_SLP-76 cd09929
Src homology 2 (SH2) domain found in B-cell linker (BLNK) protein and SH2 domain-containing ...
611-718 5.84e-08

Src homology 2 (SH2) domain found in B-cell linker (BLNK) protein and SH2 domain-containing leukocyte protein of 76 kDa (SLP-76); BLNK (also known as SLP-65 or BASH) is an important adaptor protein expressed in B-lineage cells. BLNK consists of a N-terminal sterile alpha motif (SAM) domain and a C-terminal SH2 domain. BLNK is a cytoplasmic protein, but a part of it is bound to the plasma membrane through an N-terminal leucine zipper motif and transiently bound to a cytoplasmic domain of Iga through its C-terminal SH2 domain upon B cell antigen receptor (BCR)-stimulation. A non-ITAM phosphotyrosine in Iga is necessary for the binding with the BLNK SH2 domain and/or for normal BLNK function in signaling and B cell activation. Upon phosphorylation BLNK binds Btk and PLCgamma2 through their SH2 domains and mediates PLCgamma2 activation by Btk. BLNK also binds other signaling molecules such as Vav, Grb2, Syk, and HPK1. BLNK has been shown to be necessary for BCR-mediated Ca2+ mobilization, for the activation of mitogen-activated protein kinases such as ERK, JNK, and p38 in a chicken B cell line DT40, and for activation of transcription factors such as NF-AT and NF-kappaB in human or mouse B cells. BLNK is involved in B cell development, B cell survival, activation, proliferation, and T-independent immune responses. BLNK is structurally homologous to SLP-76. SLP-76 and (linker for activation of T cells) LAT are adaptor/linker proteins in T cell antigen receptor activation and T cell development. BLNK interacts with many downstream signaling proteins that interact directly with both SLP-76 and LAT. New data suggest functional complementation of SLP-76 and LAT in T cell antigen receptor function with BLNK in BCR function. In general SH2 domains are involved in signal transduction. They typically bind pTyr-containing ligands via two surface pockets, a pTyr and hydrophobic binding pocket, allowing proteins with SH2 domains to localize to tyrosine phosphorylated sites.


Pssm-ID: 198183  Cd Length: 121  Bit Score: 51.55  E-value: 5.84e-08
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 32455248 611 EDDEDLphhDEKTWNVGSSNRNKAEN-LLRGKRDGTFLVRESSKQGC---YACSVVVDGEVKHCVINKTATGYGFAEPYN 686
Cdd:cd09929   3 EEEADL---LPKEWYAGNIDRKEAEEaLRRSNKDGTFLVRDSSGKDSsqpYTLMVLYNDKVYNIQIRFLENTRQYALGTG 79
                        90       100       110       120
                ....*....|....*....|....*....|....*....|.
gi 32455248 687 L-----YSSLKELVLHYQHTSLV----QHNDSLNVTLAYPV 718
Cdd:cd09929  80 LrgeetFSSVAEIIEHHQKTPLLlidgKDNTKDSTCLLYAA 120
SH2_Src_Lyn cd10364
Src homology 2 (SH2) domain found in Lyn; Lyn is a member of the Src non-receptor type ...
332-412 7.58e-08

Src homology 2 (SH2) domain found in Lyn; Lyn is a member of the Src non-receptor type tyrosine kinase family of proteins and is expressed in the hematopoietic cells, in neural tissues, liver, and adipose tissue. There are two alternatively spliced forms of Lyn. Lyn plays an inhibitory role in myeloid lineage proliferation. Following engagement of the B cell receptors, Lyn undergoes rapid phosphorylation and activation, triggering a cascade of signaling events mediated by Lyn phosphorylation of tyrosine residues within the immunoreceptor tyrosine-based activation motifs (ITAM) of the receptor proteins, and subsequent recruitment and activation of other kinases including Syk, phospholipase C2 (PLC2) and phosphatidyl inositol-3 kinase. These kinases play critical roles in proliferation, Ca2+ mobilization and cell differentiation. Lyn plays an essential role in the transmission of inhibitory signals through phosphorylation of tyrosine residues within the immunoreceptor tyrosine-based inhibitory motifs (ITIM) in regulatory proteins such as CD22, PIR-B and FC RIIb1. Their ITIM phosphorylation subsequently leads to recruitment and activation of phosphatases such as SHIP-1 and SHP-1 which further down modulate signaling pathways, attenuate cell activation and can mediate tolerance. Lyn also plays a role in the insulin signaling pathway. Activated Lyn phosphorylates insulin receptor substrate 1 (IRS1) leading to an increase in translocation of Glut-4 to the cell membrane and increased glucose utilization. It is the primary Src family member involved in signaling downstream of the B cell receptor. Lyn plays an unusual, 2-fold role in B cell receptor signaling; it is essential for initiation of signaling but is also later involved in negative regulation of the signal. Lyn has a unique N-terminal domain, an SH3 domain, an SH2 domain, a kinase domain and a regulatory tail, as do the other members of the family. In general SH2 domains are involved in signal transduction. They typically bind pTyr-containing ligands via two surface pockets, a pTyr and hydrophobic binding pocket, allowing proteins with SH2 domains to localize to tyrosine phosphorylated sites.


Pssm-ID: 198227  Cd Length: 101  Bit Score: 50.75  E-value: 7.58e-08
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 32455248 332 EWYWGDISREEVNEKLRDTAD--GTFLVRDASTkMHGDYTLTLR----KGGNN-KLIKIFHRD-GKYGFSDPLTFSSVVE 403
Cdd:cd10364   4 EWFFKDITRKDAERQLLAPGNsaGAFLIRESET-LKGSYSLSVRdydpQHGDViKHYKIRSLDnGGYYISPRITFPCISD 82

                ....*....
gi 32455248 404 LINHYRNES 412
Cdd:cd10364  83 MIKHYQKQS 91
SH2_DAPP1_BAM32_like cd10355
Src homology 2 domain found in dual adaptor for phosphotyrosine and 3-phosphoinositides ( ...
624-698 8.52e-08

Src homology 2 domain found in dual adaptor for phosphotyrosine and 3-phosphoinositides ( DAPP1)/B lymphocyte adaptor molecule of 32 kDa (Bam32)-like proteins; DAPP1/Bam32 contains a putative myristoylation site at its N-terminus, followed by a SH2 domain, and a pleckstrin homology (PH) domain at its C-terminus. DAPP1 could potentially be recruited to the cell membrane by any of these domains. Its putative myristoylation site could facilitate the interaction of DAPP1 with the lipid bilayer. Its SH2 domain may also interact with phosphotyrosine residues on membrane-associated proteins such as activated tyrosine kinase receptors. And finally its PH domain exhibits a high-affinity interaction with the PtdIns(3,4,5)P(3) PtdIns(3,4)P(2) second messengers produced at the cell membrane following the activation of PI 3-kinases. DAPP1 is thought to interact with both tyrosine phosphorylated proteins and 3-phosphoinositides and therefore may play a role in regulating the location and/or activity of such proteins(s) in response to agonists that elevate PtdIns(3,4,5)P(3) and PtdIns(3,4)P(2). This protein is likely to play an important role in triggering signal transduction pathways that lie downstream from receptor tyrosine kinases and PI 3-kinase. It is likely that DAPP1 functions as an adaptor to recruit other proteins to the plasma membrane in response to extracellular signals. In general SH2 domains are involved in signal transduction. They typically bind pTyr-containing ligands via two surface pockets, a pTyr and hydrophobic binding pocket, allowing proteins with SH2 domains to localize to tyrosine phosphorylated sites.


Pssm-ID: 198218  Cd Length: 92  Bit Score: 50.55  E-value: 8.52e-08
                        10        20        30        40        50        60        70
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 32455248 624 WNVGSSNRNKAEN-LLRGKRDGTFLVRES-SKQGCYACSVVVDGEVKHCVInkTATGYGFAEPYNLYSSLKELVLHY 698
Cdd:cd10355   8 WYHGNLTRHAAEAlLLSNGVDGSYLLRNSnEGTGLFSLSVRAKDSVKHFHV--EYTGYSFKFGFNEFSSLQDFVKHF 82
SH2_Cterm_shark_like cd10348
C-terminal Src homology 2 (SH2) domain found in SH2 domains, ANK, and kinase domain (shark) ...
332-408 1.02e-07

C-terminal Src homology 2 (SH2) domain found in SH2 domains, ANK, and kinase domain (shark) proteins; These non-receptor protein-tyrosine kinases contain two SH2 domains, five ankyrin (ANK)-like repeats, and a potential tyrosine phosphorylation site in its carboxyl-terminal tail which resembles the phosphorylation site in members of the src family. Like, mammalian non-receptor protein-tyrosine kinases, ZAP-70 and syk proteins, they do not have SH3 domains. However, the presence of ANK makes these unique among protein-tyrosine kinases. Both tyrosine kinases and ANK repeats have been shown to transduce developmental signals, and SH2 domains are known to participate intimately in tyrosine kinase signaling. These tyrosine kinases are believed to be involved in epithelial cell polarity. The members of this family include the shark (SH2 domains, ANK, and kinase domain) gene in Drosophila and yellow fever mosquitos, as well as the hydra protein HTK16. Drosophila Shark is proposed to transduce intracellularly the Crumbs, a protein necessary for proper organization of ectodermal epithelia, intercellular signal. In general SH2 domains are involved in signal transduction. They typically bind pTyr-containing ligands via two surface pockets, a pTyr and hydrophobic binding pocket, allowing proteins with SH2 domains to localize to tyrosine phosphorylated sites.


Pssm-ID: 198211  Cd Length: 86  Bit Score: 50.11  E-value: 1.02e-07
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 32455248 332 EWYWGDISREEVNEKLRD--TADGTFLVRdASTKMHGDYTLTLRKGGNNKLIKIFHRDGKYGFSD--PLtFSSVVELINH 407
Cdd:cd10348   1 QWLHGALDRNEAVEILKQkaDADGSFLVR-YSRRRPGGYVLTLVYENHVYHFEIQNRDDKWFYIDdgPY-FESLEHLIEH 78

                .
gi 32455248 408 Y 408
Cdd:cd10348  79 Y 79
SH2_Vav1 cd10405
Src homology 2 (SH2) domain found in the Vav1 proteins; Proto-oncogene vav is a member of the ...
333-427 1.64e-07

Src homology 2 (SH2) domain found in the Vav1 proteins; Proto-oncogene vav is a member of the Dbl family of guanine nucleotide exchange factors (GEF) for the Rho family of GTP binding proteins. All vavs are activated by tyrosine phosphorylation leading to their activation. There are three Vav mammalian family members: Vav1 which is expressed in the hematopoietic system, and Vav2 and Vav3 are more ubiquitously expressed. Vav1 plays a role in T-cell and B-cell development and activation. It has been identified as the specific binding partner of Nef proteins from HIV-1, resulting in morphological changes, cytoskeletal rearrangements, and the JNK/SAPK signaling cascade, leading to increased levels of viral transcription and replication. Vav1 has been shown to interact with Ku70, PLCG1, Lymphocyte cytosolic protein 2, Janus kinase 2, SIAH2, S100B, Abl gene, ARHGDIB, SHB, PIK3R1, PRKCQ, Grb2, MAPK1, Syk, Linker of activated T cells, Cbl gene and EZH2. Vav proteins are involved in several processes that require cytoskeletal reorganization, such as the formation of the immunological synapse (IS), phagocytosis, platelet aggregation, spreading, and transformation. Vavs function as guanine nucleotide exchange factors (GEFs) for the Rho/Rac family of GTPases. Vav family members have several conserved motifs/domains including: a leucine-rich region, a leucine-zipper, a calponin homology (CH) domain, an acidic domain, a Dbl-homology (DH) domain, a pleckstrin homology (PH) domain, a cysteine-rich domain, 2 SH3 domains, a proline-rich region, and a SH2 domain. Vavs are the only known Rho GEFs that have both the DH/PH motifs and SH2/SH3 domains in the same protein. The leucine-rich helix-loop-helix (HLH) domain is thought to be involved in protein heterodimerization with other HLH proteins and it may function as a negative regulator by forming inactive heterodimers. The CH domain is usually involved in the association with filamentous actin, but in Vav it controls NFAT stimulation, Ca2+ mobilization, and its transforming activity. Acidic domains are involved in protein-protein interactions and contain regulatory tyrosines. The DH domain is a GDP-GTP exchange factor on Rho/Rac GTPases. The PH domain in involved in interactions with GTP-binding proteins, lipids and/or phosphorylated serine/threonine residues. The SH3 domain is involved in localization of proteins to specific sites within the cell interacting with protein with proline-rich sequences. The SH2 domain mediates a high affinity interaction with tyrosine phosphorylated proteins. In general SH2 domains are involved in signal transduction. They typically bind pTyr-containing ligands via two surface pockets, a pTyr and hydrophobic binding pocket, allowing proteins with SH2 domains to localize to tyrosine phosphorylated sites.


Pssm-ID: 198268  Cd Length: 103  Bit Score: 50.01  E-value: 1.64e-07
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 32455248 333 WYWGDISREEVNEKLRDTADGTFLVRDaSTKMHGDYTLTLRKGGNNKLIKIFHRDGKYGFSDPLTFSSVVELINHYRNES 412
Cdd:cd10405   7 WYAGPMERAGAESILANRSDGTYLVRQ-RVKDAAEFAISIKYNVEVKHIKIMTAEGLYRITEKKAFRGLTELVEFYQQNS 85
                        90
                ....*....|....*
gi 32455248 413 LAQYNPKLDVKLLYP 427
Cdd:cd10405  86 LKDCFKSLDTTLQFP 100
SH2_Nterm_shark_like cd10347
N-terminal Src homology 2 (SH2) domain found in SH2 domains, ANK, and kinase domain (shark) ...
624-698 1.71e-07

N-terminal Src homology 2 (SH2) domain found in SH2 domains, ANK, and kinase domain (shark) proteins; These non-receptor protein-tyrosine kinases contain two SH2 domains, five ankyrin (ANK)-like repeats, and a potential tyrosine phosphorylation site in the carboxyl-terminal tail which resembles the phosphorylation site in members of the src family. Like, mammalian non-receptor protein-tyrosine kinases, ZAP-70 and syk proteins, they do not have SH3 domains. However, the presence of ANK makes these unique among protein-tyrosine kinases. Both tyrosine kinases and ANK repeats have been shown to transduce developmental signals, and SH2 domains are known to participate intimately in tyrosine kinase signaling. These tyrosine kinases are believed to be involved in epithelial cell polarity. The members of this family include the shark (SH2 domains, ANK, and kinase domain) gene in Drosophila and yellow fever mosquitos, as well as the hydra protein HTK16. Drosophila Shark is proposed to transduce intracellularly the Crumbs, a protein necessary for proper organization of ectodermal epithelia, intercellular signal. In general SH2 domains are involved in signal transduction. They typically bind pTyr-containing ligands via two surface pockets, a pTyr and hydrophobic binding pocket, allowing proteins with SH2 domains to localize to tyrosine phosphorylated sites.


Pssm-ID: 198210  Cd Length: 81  Bit Score: 49.30  E-value: 1.71e-07
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 32455248 624 WNVGSSNRNKAENLL--RGKRDGTFLVRES-SKQGCYACSVVVDGEVKHCVINKTATGYGFA--EPYNLYsSLKELVLHY 698
Cdd:cd10347   3 WYHGKISREVAEALLlrEGGRDGLFLVREStSAPGDYVLSLLAQGEVLHYQIRRHGEDAFFSddGPLIFH-GLDTLIEHY 81
SH2_C-SH2_PLC_gamma_like cd09932
C-terminal Src homology 2 (C-SH2) domain in Phospholipase C gamma; Phospholipase C gamma is a ...
332-430 2.08e-07

C-terminal Src homology 2 (C-SH2) domain in Phospholipase C gamma; Phospholipase C gamma is a signaling molecule that is recruited to the C-terminal tail of the receptor upon autophosphorylation of a highly conserved tyrosine. PLCgamma is composed of a Pleckstrin homology (PH) domain followed by an elongation factor (EF) domain, 2 catalytic regions of PLC domains that flank 2 tandem SH2 domains (N-SH2, C-SH2), and ending with a SH3 domain and C2 domain. N-SH2 SH2 domain-mediated interactions represent a crucial step in transmembrane signaling by receptor tyrosine kinases. SH2 domains recognize phosphotyrosine (pY) in the context of particular sequence motifs in receptor phosphorylation sites. Both N-SH2 and C-SH2 have a very similar binding affinity to pY. But in growth factor stimulated cells these domains bind to different target proteins. N-SH2 binds to pY containing sites in the C-terminal tails of tyrosine kinases and other receptors. Recently it has been shown that this interaction is mediated by phosphorylation-independent interactions between a secondary binding site found exclusively on the N-SH2 domain and a region of the FGFR1 tyrosine kinase domain. This secondary site on the SH2 cooperates with the canonical pY site to regulate selectivity in mediating a specific cellular process. C-SH2 binds to an intramolecular site on PLCgamma itself which allows it to hydrolyze phosphatidylinositol-4,5-bisphosphate into diacylglycerol and inositol triphosphate. These then activate protein kinase C and release calcium. In general SH2 domains are involved in signal transduction. They typically bind pTyr-containing ligands via two surface pockets, a pTyr and hydrophobic binding pocket, allowing proteins with SH2 domains to localize to tyrosine phosphorylated sites.


Pssm-ID: 198186  Cd Length: 104  Bit Score: 49.57  E-value: 2.08e-07
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 32455248 332 EWYWGDISREEVNEKL-RDTADGTFLVRDASTKMHGdYTLTLRKGGNNKLIKIfHRDGKYGFSDPLTFSSVVELINHYRN 410
Cdd:cd09932   5 EWFHANLTREQAEEMLmRVPRDGAFLVRPSETDPNS-FAISFRAEGKIKHCRI-KQEGRLFVIGTSQFESLVELVSYYEK 82
                        90       100
                ....*....|....*....|
gi 32455248 411 ESLAQynpklDVKLLYPVSK 430
Cdd:cd09932  83 HPLYR-----KIKLRYPVNE 97
SH2_CRK_like cd09926
Src homology 2 domain found in cancer-related signaling adaptor protein CRK; SH2 domain in the ...
620-674 2.69e-07

Src homology 2 domain found in cancer-related signaling adaptor protein CRK; SH2 domain in the CRK proteins. CRKI (SH2-SH3) and CRKII (SH2-SH3-SH3) are splicing isoforms of the oncoprotein CRK. CRKs regulate transcription and cytoskeletal reorganization for cell growth and motility by linking tyrosine kinases to small G proteins. The SH2 domain of CRK associates with tyrosine-phosphorylated receptors or components of focal adhesions, such as p130Cas and paxillin. CRK transmits signals to small G proteins through effectors that bind its SH3 domain, such as C3G, the guanine-nucleotide exchange factor (GEF) for Rap1 and R-Ras, and DOCK180, the GEF for Rac6. The binding of p130Cas to the CRK-C3G complex activates Rap1, leading to regulation of cell adhesion, and activates R-Ras, leading to JNK-mediated activation of cell proliferation, whereas the binding of CRK DOCK180 induces Rac1-mediated activation of cellular migration. The activity of the different splicing isoforms varies greatly with CRKI displaying substantial transforming activity, CRKII less so, and phosphorylated CRKII with no biological activity whatsoever. CRKII has a linker region with a phosphorylated Tyr and an additional C-terminal SH3 domain. The phosphorylated Tyr creates a binding site for its SH2 domain which disrupts the association between CRK and its SH2 target proteins. In general SH2 domains are involved in signal transduction. They typically bind pTyr-containing ligands via two surface pockets, a pTyr and hydrophobic binding pocket, allowing proteins with SH2 domains to localize to tyrosine phosphorylated sites.


Pssm-ID: 198180 [Multi-domain]  Cd Length: 106  Bit Score: 49.39  E-value: 2.69e-07
                        10        20        30        40        50
                ....*....|....*....|....*....|....*....|....*....|....*.
gi 32455248 620 DEKTWNVGSSNRNKAENLLRGKRDGTFLVRESSK-QGCYACSVVVDGEVKHCVINK 674
Cdd:cd09926   5 DRSSWYFGPMSRQEAQELLQGQRHGVFLVRDSSTiPGDYVLSVSENSRVSHYIINS 60
RhoGAP-ARHGAP11A cd04394
RhoGAP-ARHGAP11A: RhoGAP (GTPase-activator protein [GAP] for Rho-like small GTPases) domain of ...
129-294 2.75e-07

RhoGAP-ARHGAP11A: RhoGAP (GTPase-activator protein [GAP] for Rho-like small GTPases) domain of ArhGAP11A-like proteins. The mouse homolog of human ArhGAP11A has been detected as a gene exclusively expressed in immature ganglion cells, potentially playing a role in retinal development. The exact function of ArhGAP11A is unknown. Small GTPases cluster into distinct families, and all act as molecular switches, active in their GTP-bound form but inactive when GDP-bound. The Rho family of GTPases activates effectors involved in a wide variety of developmental processes, including regulation of cytoskeleton formation, cell proliferation and the JNK signaling pathway. GTPases generally have a low intrinsic GTPase hydrolytic activity but there are family-specific groups of GAPs that enhance the rate of GTP hydrolysis by several orders of magnitude.


Pssm-ID: 239859 [Multi-domain]  Cd Length: 202  Bit Score: 51.70  E-value: 2.75e-07
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 32455248 129 PPLLIKLVEAIEKKgLECSTLYRTQSS-SNLAELRQLLD----CDTPSvdlEMIDVhvlADAFKRYLLDLPNPVIPAAvY 203
Cdd:cd04394  21 PKFLVDACTFLLDH-LSTEGLFRKSGSvVRQKELKAKLEggeaCLSSA---LPCDV---AGLLKQFFRELPEPLLPYD-L 92
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 32455248 204 SEMISLAPEVQSSEEYIQLLkkLIRSPSIPHQYWLTLQYLLKHFFKLSQTSSKNLLNARVLSEIFSPMLFRFS---AASS 280
Cdd:cd04394  93 HEALLKAQELPTDEERKSAT--LLLTCLLPDEHVNTLRYFFSFLYDVAQRCSENKMDSSNLAVIFAPNLFQSEeggEKMS 170
                       170
                ....*....|....*...
gi 32455248 281 DNTENLIK----VIEILI 294
Cdd:cd04394 171 SSTEKRLRlqaaVVQTLI 188
SH2_Cterm_RasGAP cd10354
C-terminal Src homology 2 (SH2) domain found in Ras GTPase-activating protein 1 (GAP); RasGAP ...
332-408 2.77e-07

C-terminal Src homology 2 (SH2) domain found in Ras GTPase-activating protein 1 (GAP); RasGAP is part of the GAP1 family of GTPase-activating proteins. The protein is located in the cytoplasm and stimulates the GTPase activity of normal RAS p21, but not its oncogenic counterpart. Acting as a suppressor of RAS function, the protein enhances the weak intrinsic GTPase activity of RAS proteins resulting in RAS inactivation, thereby allowing control of cellular proliferation and differentiation. Mutations leading to changes in the binding sites of either protein are associated with basal cell carcinomas. Alternative splicing results in two isoforms. The shorter isoform which lacks the N-terminal hydrophobic region, has the same activity, and is expressed in placental tissues. In general longer isoform contains 2 SH2 domains, a SH3 domain, a pleckstrin homology (PH) domain, and a calcium-dependent phospholipid-binding C2 domain. The C-terminus contains the catalytic domain of RasGap which catalyzes the activation of Ras by hydrolyzing GTP-bound active Ras into an inactive GDP-bound form of Ras. This model contains the C-terminal SH2 domain. In general SH2 domains are involved in signal transduction. They typically bind pTyr-containing ligands via two surface pockets, a pTyr and hydrophobic binding pocket, allowing proteins with SH2 domains to localize to tyrosine phosphorylated sites.


Pssm-ID: 198217  Cd Length: 77  Bit Score: 48.57  E-value: 2.77e-07
                        10        20        30        40        50        60        70
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 32455248 332 EWYWGDISREEVNEKLRDTA-DGTFLVRDaSTKMHGDYTLTLRKGGNNKLIKIFHRDGKYGFSDPLTFSSVVELINHY 408
Cdd:cd10354   1 IWFHGKISREEAYNMLVKVGgPGSFLVRE-SDNTPGDYSLSFRVNEGIKHFKIIPTGNNQFMMGGRYFSSLDDVIDRY 77
RhoGAP-p50rhoGAP cd04404
RhoGAP-p50rhoGAP: RhoGAP (GTPase-activator protein [GAP] for Rho-like small GTPases) domain of ...
109-279 2.86e-07

RhoGAP-p50rhoGAP: RhoGAP (GTPase-activator protein [GAP] for Rho-like small GTPases) domain of p50RhoGAP-like proteins; p50RhoGAP, also known as RhoGAP-1, contains a C-terminal RhoGAP domain and an N-terminal Sec14 domain which binds phosphatidylinositol 3,4,5-trisphosphate (PtdIns(3,4,5)P3). It is ubiquitously expressed and preferentially active on Cdc42. This subgroup also contains closely related ARHGAP8. Small GTPases cluster into distinct families, and all act as molecular switches, active in their GTP-bound form but inactive when GDP-bound. The Rho family of GTPases activates effectors involved in a wide variety of developmental processes, including regulation of cytoskeleton formation, cell proliferation and the JNK signaling pathway. GTPases generally have a low intrinsic GTPase hydrolytic activity but there are family-specific groups of GAPs that enhance the rate of GTP hydrolysis by several orders of magnitude.


Pssm-ID: 239869 [Multi-domain]  Cd Length: 195  Bit Score: 51.57  E-value: 2.86e-07
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 32455248 109 EQQALTLPDLAEQFAPPDIAPPLLIKLVEAIEKKGLECSTLYR-TQSSSNLAELRQLLDCDTPsVDLE-MIDVHVLADAF 186
Cdd:cd04404   4 QQFGVSLQFLKEKNPEQEPIPPVVRETVEYLQAHALTTEGIFRrSANTQVVKEVQQKYNMGEP-VDFDqYEDVHLPAVIL 82
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 32455248 187 KRYLLDLPNPVIPAAVYSEMISLA--PEVQSSEEYIQLLKKLirspsiPHQYWLTLQYLLKHFFKLSQTSSKNLLNARVL 264
Cdd:cd04404  83 KTFLRELPEPLLTFDLYDDIVGFLnvDKEERVERVKQLLQTL------PEENYQVLKYLIKFLVQVSAHSDQNKMTNSNL 156
                       170
                ....*....|....*
gi 32455248 265 SEIFSPMLFRFSAAS 279
Cdd:cd04404 157 AVVFGPNLLWAKDAS 171
SH2_Grb2_like cd09941
Src homology 2 domain found in Growth factor receptor-bound protein 2 (Grb2) and similar ...
620-702 2.96e-07

Src homology 2 domain found in Growth factor receptor-bound protein 2 (Grb2) and similar proteins; The adaptor proteins here include homologs Grb2 in humans, Sex muscle abnormal protein 5 (Sem-5) in Caenorhabditis elegans, and Downstream of receptor kinase (drk) in Drosophila melanogaster. They are composed of one SH2 and two SH3 domains. Grb2/Sem-5/drk regulates the Ras pathway by linking the tyrosine kinases to the Ras guanine nucleotide releasing protein Sos, which converts Ras to the active GTP-bound state. The SH2 domain of Grb2/Sem-5/drk binds class II phosphotyrosyl peptides while its SH3 domain binds to Sos and Sos-derived, proline-rich peptides. Besides it function in Ras signaling, Grb2 is also thought to play a role in apoptosis. Unlike most SH2 structures in which the peptide binds in an extended conformation (such that the +3 peptide residue occupies a hydrophobic pocket in the protein, conferring a modest degree of selectivity), Grb2 forms several hydrogen bonds via main chain atoms with the side chain of +2 Asn. In general SH2 domains are involved in signal transduction. They typically bind pTyr-containing ligands via two surface pockets, a pTyr and hydrophobic binding pocket, allowing proteins with SH2 domains to localize to tyrosine phosphorylated sites.


Pssm-ID: 199828  Cd Length: 95  Bit Score: 48.81  E-value: 2.96e-07
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 32455248 620 DEKTWNVGSSNRNKAENLLRG-KRDGTFLVRES-SKQGCYACSVVVDGEVKHCVINKTATGYgfaepYNLY----SSLKE 693
Cdd:cd09941   1 KPHPWFHGKISRAEAEEILMNqRPDGAFLIRESeSSPGDFSLSVKFGNDVQHFKVLRDGAGK-----YFLWvvkfNSLNE 75

                ....*....
gi 32455248 694 LVLHYQHTS 702
Cdd:cd09941  76 LVDYHRTTS 84
SH3_UBASH3 cd11791
Src homology 3 domain of Ubiquitin-associated and SH3 domain-containing proteins, also called ...
8-75 3.24e-07

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: 47.68  E-value: 3.24e-07
                        10        20        30        40        50        60
                ....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 32455248   8 YRALYDYKKEREEDIDLHLGDILTVNkgslvalgfSDGQEARPEeiGWLNGYNETTGERGDFPGTYVE 75
Cdd:cd11791   2 LRVLYPYTPQEEDELELVPGDYIYVS---------PEELDSSSD--GWVEGTSWLTGCSGLLPENYTE 58
SH2_N-SH2_Zap70_Syk_like cd09938
N-terminal Src homology 2 (SH2) domain found in Zeta-chain-associated protein kinase 70 ...
333-412 3.28e-07

N-terminal Src homology 2 (SH2) domain found in Zeta-chain-associated protein kinase 70 (ZAP-70) and Spleen tyrosine kinase (Syk) proteins; ZAP-70 and Syk comprise a family of hematopoietic cell specific protein tyrosine kinases (PTKs) that are required for antigen and antibody receptor function. ZAP-70 is expressed in T and natural killer (NK) cells and Syk is expressed in B cells, mast cells, polymorphonuclear leukocytes, platelets, macrophages, and immature T cells. They are required for the proper development of T and B cells, immune receptors, and activating NK cells. They consist of two N-terminal Src homology 2 (SH2) domains and a C-terminal kinase domain separated from the SH2 domains by a linker or hinge region. Phosphorylation of both tyrosine residues within the Immunoreceptor Tyrosine-based Activation Motifs (ITAM; consensus sequence Yxx[LI]x(7,8)Yxx[LI]) by the Src-family PTKs is required for efficient interaction of ZAP-70 and Syk with the receptor subunits and for receptor function. ZAP-70 forms two phosphotyrosine binding pockets, one of which is shared by both SH2 domains. In Syk the two SH2 domains do not form such a phosphotyrosine-binding site. The SH2 domains here are believed to function independently. In addition, the two SH2 domains of Syk display flexibility in their relative orientation, allowing Syk to accommodate a greater variety of spacing sequences between the ITAM phosphotyrosines and singly phosphorylated non-classical ITAM ligands. This model contains the N-terminus SH2 domains of both Syk and Zap70. In general SH2 domains are involved in signal transduction. They typically bind pTyr-containing ligands via two surface pockets, a pTyr and hydrophobic binding pocket, allowing proteins with SH2 domains to localize to tyrosine phosphorylated sites.


Pssm-ID: 198191  Cd Length: 104  Bit Score: 48.93  E-value: 3.28e-07
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 32455248 333 WYWGDISREEVNEKLRDT--ADGTFLVRDaSTKMHGDYTLTLRKGGnnkliKIFHR------DGKYGFSDPLTFSSVVEL 404
Cdd:cd09938   3 FFYGSITREEAEEYLKLAgmSDGLFLLRQ-SLRSLGGYVLSVCHGR-----KFHHYtierqlNGTYAIAGGKAHCGPAEL 76

                ....*...
gi 32455248 405 INHYRNES 412
Cdd:cd09938  77 CEYHSTDL 84
SH2_Grb2_like cd09941
Src homology 2 domain found in Growth factor receptor-bound protein 2 (Grb2) and similar ...
333-412 3.49e-07

Src homology 2 domain found in Growth factor receptor-bound protein 2 (Grb2) and similar proteins; The adaptor proteins here include homologs Grb2 in humans, Sex muscle abnormal protein 5 (Sem-5) in Caenorhabditis elegans, and Downstream of receptor kinase (drk) in Drosophila melanogaster. They are composed of one SH2 and two SH3 domains. Grb2/Sem-5/drk regulates the Ras pathway by linking the tyrosine kinases to the Ras guanine nucleotide releasing protein Sos, which converts Ras to the active GTP-bound state. The SH2 domain of Grb2/Sem-5/drk binds class II phosphotyrosyl peptides while its SH3 domain binds to Sos and Sos-derived, proline-rich peptides. Besides it function in Ras signaling, Grb2 is also thought to play a role in apoptosis. Unlike most SH2 structures in which the peptide binds in an extended conformation (such that the +3 peptide residue occupies a hydrophobic pocket in the protein, conferring a modest degree of selectivity), Grb2 forms several hydrogen bonds via main chain atoms with the side chain of +2 Asn. In general SH2 domains are involved in signal transduction. They typically bind pTyr-containing ligands via two surface pockets, a pTyr and hydrophobic binding pocket, allowing proteins with SH2 domains to localize to tyrosine phosphorylated sites.


Pssm-ID: 199828  Cd Length: 95  Bit Score: 48.81  E-value: 3.49e-07
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 32455248 333 WYWGDISREEVNEKLRDTA-DGTFLVRDASTKmHGDYTLTLRKGGNNKLIKIFhRD--GKYGFSDpLTFSSVVELINHYR 409
Cdd:cd09941   5 WFHGKISRAEAEEILMNQRpDGAFLIRESESS-PGDFSLSVKFGNDVQHFKVL-RDgaGKYFLWV-VKFNSLNELVDYHR 81

                ...
gi 32455248 410 NES 412
Cdd:cd09941  82 TTS 84
SH2_SLAP cd10344
Src homology 2 domain found in Src-like adaptor proteins; SLAP belongs to the subfamily of ...
630-698 4.81e-07

Src homology 2 domain found in Src-like adaptor proteins; SLAP belongs to the subfamily of adapter proteins that negatively regulate cellular signaling initiated by tyrosine kinases. It has a myristylated N-terminus, SH3 and SH2 domains with high homology to Src family tyrosine kinases, and a unique C-terminal tail, which is important for c-Cbl binding. SLAP negatively regulates platelet-derived growth factor (PDGF)-induced mitogenesis in fibroblasts and regulates F-actin assembly for dorsal ruffles formation. c-Cbl mediated SLAP inhibition towards actin remodeling. Moreover, SLAP enhanced PDGF-induced c-Cbl phosphorylation by SFK. In contrast, SLAP mitogenic inhibition was not mediated by c-Cbl, but it rather involved a competitive mechanism with SFK for PDGF-receptor (PDGFR) association and mitogenic signaling. Accordingly, phosphorylation of the Src mitogenic substrates Stat3 and Shc were reduced by SLAP. Thus, we concluded that SLAP regulates PDGFR signaling by two independent mechanisms: a competitive mechanism for PDGF-induced Src mitogenic signaling and a non-competitive mechanism for dorsal ruffles formation mediated by c-Cbl. SLAP is a hematopoietic adaptor containing Src homology (SH)3 and SH2 motifs and a unique carboxy terminus. Unlike c-Src, SLAP lacks a tyrosine kinase domain. Unlike c-Src, SLAP does not impact resorptive function of mature osteoclasts but induces their early apoptosis. SLAP negatively regulates differentiation of osteoclasts and proliferation of their precursors. Conversely, SLAP decreases osteoclast death by inhibiting activation of caspase 3. In general SH2 domains are involved in signal transduction. They typically bind pTyr-containing ligands via two surface pockets, a pTyr and hydrophobic binding pocket, allowing proteins with SH2 domains to localize to tyrosine phosphorylated sites.


Pssm-ID: 198207  Cd Length: 104  Bit Score: 48.64  E-value: 4.81e-07
                        10        20        30        40        50        60        70
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 32455248 630 NRNKAENLLR--GKRDGTFLVRES-SKQGCYACSV-----VVDGEVKHCVINKTATGYGFAEPYNLYSSLKELVLHY 698
Cdd:cd10344  18 SREKAEELLMlpGNQVGSFLIRESeTRRGCYSLSVrhrgsQSRDSVKHYRIFRLDNGWFYISPRLTFQCLEDMVNHY 94
SH2_Src_HCK cd10363
Src homology 2 (SH2) domain found in HCK; HCK is a member of the Src non-receptor type ...
332-429 5.00e-07

Src homology 2 (SH2) domain found in HCK; HCK is a member of the Src non-receptor type tyrosine kinase family of proteins and is expressed in hemopoietic cells. HCK is proposed to couple the Fc receptor to the activation of the respiratory burst. It may also play a role in neutrophil migration and in the degranulation of neutrophils. It has two different translational starts that have different subcellular localization. HCK has been shown to interact with BCR gene, ELMO1 Cbl gene, RAS p21 protein activator 1, RASA3, Granulocyte colony-stimulating factor receptor, ADAM15 and RAPGEF1. Like the other members of the Src family the SH2 domain in addition to binding the target, also plays an autoinhibitory role by binding to its C-terminal tail. In general SH2 domains are involved in signal transduction. HCK has a unique N-terminal domain, an SH3 domain, an SH2 domain, a kinase domain and a regulatory tail, as do the other members of the family. They typically bind pTyr-containing ligands via two surface pockets, a pTyr and hydrophobic binding pocket, allowing proteins with SH2 domains to localize to tyrosine phosphorylated sites.


Pssm-ID: 198226  Cd Length: 104  Bit Score: 48.42  E-value: 5.00e-07
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 32455248 332 EWYWGDISREEVNEKLRDTAD--GTFLVRDASTKmHGDYTLTLR-----KGGNNKLIKIFHRD-GKYGFSDPLTFSSVVE 403
Cdd:cd10363   4 EWFFKGISRKDAERQLLAPGNmlGSFMIRDSETT-KGSYSLSVRdydpqHGDTVKHYKIRTLDnGGFYISPRSTFSTLQE 82
                        90       100
                ....*....|....*....|....*...
gi 32455248 404 LINHYR--NESLAQynpkldvKLLYPVS 429
Cdd:cd10363  83 LVDHYKkgNDGLCQ-------KLSVPCM 103
SH2_Src_Frk cd10369
Src homology 2 (SH2) domain found in the Fyn-related kinase (Frk); Frk is a member of the Src ...
624-717 5.11e-07

Src homology 2 (SH2) domain found in the Fyn-related kinase (Frk); Frk is a member of the Src non-receptor type tyrosine kinase family of proteins. The Frk subfamily is composed of Frk/Rak and Iyk/Bsk/Gst. It is expressed primarily epithelial cells. Frk is a nuclear protein and may function during G1 and S phase of the cell cycle and suppress growth. Unlike the other Src members it lacks a glycine at position 2 of SH4 which is important for addition of a myristic acid moiety that is involved in targeting Src PTKs to cellular membranes. FRK and SHB exert similar effects when overexpressed in rat phaeochromocytoma (PC12) and beta-cells, where both induce PC12 cell differentiation and beta-cell proliferation. Under conditions that cause beta-cell degeneration these proteins augment beta-cell apoptosis. The FRK-SHB responses involve FAK and insulin receptor substrates (IRS) -1 and -2. Frk has been demonstrated to interact with retinoblastoma protein. Frk regulates PTEN protein stability by phosphorylating PTEN, which in turn prevents PTEN degradation. Frk also plays a role in regulation of embryonal pancreatic beta cell formation. Frk has a unique N-terminal domain, an SH3 domain, an SH2 domain, a kinase domain and a regulatory tail, as do the other members of the family. Like the other members of the Src family the SH2 domain in addition to binding the target, also plays an autoinhibitory role by binding to its activation loop. The tryosine involved is at the same site as the tyrosine involved in the autophosphorylation of Src. In general SH2 domains are involved in signal transduction. They typically bind pTyr-containing ligands via two surface pockets, a pTyr and hydrophobic binding pocket, allowing proteins with SH2 domains to localize to tyrosine phosphorylated sites.


Pssm-ID: 199831  Cd Length: 96  Bit Score: 48.34  E-value: 5.11e-07
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 32455248 624 WNVGSSNRNKAEN--LLRGKRDGTFLVRES-SKQGCYACSVVVDGEVKHCVINKTATGYGFAEPYNLYSSLKELVLHYQH 700
Cdd:cd10369   5 WFFGAIKRADAEKqlLYSENQTGAFLIRESeSQKGEFSLSVLDGGVVKHYRIRRLDEGGFFLTRRKTFSTLNEFVNYYTT 84
                        90
                ....*....|....*..
gi 32455248 701 TSlvqhnDSLNVTLAYP 717
Cdd:cd10369  85 TS-----DGLCVKLGKP 96
SH2_Src_Src cd10365
Src homology 2 (SH2) domain found in tyrosine kinase sarcoma (Src); Src is a member of the Src ...
329-412 5.71e-07

Src homology 2 (SH2) domain found in tyrosine kinase sarcoma (Src); Src is a member of the Src non-receptor type tyrosine kinase family of proteins. Src is thought to play a role in the regulation of embryonic development and cell growth. Members here include v-Src and c-Src. v-Src lacks the C-terminal inhibitory phosphorylation site and is therefore constitutively active as opposed to normal cellular src (c-Src) which is only activated under certain circumstances where it is required (e.g. growth factor signaling). v-Src is an oncogene whereas c-Src is a proto-oncogene. c-Src consists of three domains, an N-terminal SH3 domain, a central SH2 domain and a tyrosine kinase domain. The SH2 and SH3 domains work together in the auto-inhibition of the kinase domain. The phosphorylation of an inhibitory tyrosine near the c-terminus of the protein produces a binding site for the SH2 domain which then facilitates binding of the SH3 domain to a polyproline site within the linker between the SH2 domain and the kinase domain. Binding of the SH3 domain inactivates the enzyme. This allows for multiple mechanisms for c-Src activation: dephosphorylation of the C-terminal tyrosine by a protein tyrosine phosphatase, binding of the SH2 domain by a competitive phospho-tyrosine residue, or competitive binding of a polyproline binding site to the SH3 domain. Unlike most other Src members Src lacks cysteine residues in the SH4 domain that undergo palmitylation. Serine and threonine phosphorylation sites have also been identified in the unique domains of Src and are believed to modulate protein-protein interactions or regulate catalytic activity. Alternatively spliced forms of Src, which contain 6- or 11-amino acid insertions in the SH3 domain, are expressed in CNS neurons. c-Src has a unique N-terminal domain, an SH3 domain, an SH2 domain, a kinase domain and a regulatory tail, as do the other members of the family. In general SH2 domains are involved in signal transduction. They typically bind pTyr-containing ligands via two surface pockets, a pTyr and hydrophobic binding pocket, allowing proteins with SH2 domains to localize to tyrosine phosphorylated sites.


Pssm-ID: 198228  Cd Length: 101  Bit Score: 48.51  E-value: 5.71e-07
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 32455248 329 QDAEWYWGDISREEVNEKLRDTAD--GTFLVRDASTkMHGDYTLTL-----RKGGNNKLIKIFHRD-GKYGFSDPLTFSS 400
Cdd:cd10365   1 QAEEWYFGKITRRESERLLLNAENprGTFLVRESET-TKGAYCLSVsdfdnAKGLNVKHYKIRKLDsGGFYITSRTQFNS 79
                        90
                ....*....|..
gi 32455248 401 VVELINHYRNES 412
Cdd:cd10365  80 LQQLVAYYSKHA 91
SH2_Src_Src cd10365
Src homology 2 (SH2) domain found in tyrosine kinase sarcoma (Src); Src is a member of the Src ...
624-710 7.57e-07

Src homology 2 (SH2) domain found in tyrosine kinase sarcoma (Src); Src is a member of the Src non-receptor type tyrosine kinase family of proteins. Src is thought to play a role in the regulation of embryonic development and cell growth. Members here include v-Src and c-Src. v-Src lacks the C-terminal inhibitory phosphorylation site and is therefore constitutively active as opposed to normal cellular src (c-Src) which is only activated under certain circumstances where it is required (e.g. growth factor signaling). v-Src is an oncogene whereas c-Src is a proto-oncogene. c-Src consists of three domains, an N-terminal SH3 domain, a central SH2 domain and a tyrosine kinase domain. The SH2 and SH3 domains work together in the auto-inhibition of the kinase domain. The phosphorylation of an inhibitory tyrosine near the c-terminus of the protein produces a binding site for the SH2 domain which then facilitates binding of the SH3 domain to a polyproline site within the linker between the SH2 domain and the kinase domain. Binding of the SH3 domain inactivates the enzyme. This allows for multiple mechanisms for c-Src activation: dephosphorylation of the C-terminal tyrosine by a protein tyrosine phosphatase, binding of the SH2 domain by a competitive phospho-tyrosine residue, or competitive binding of a polyproline binding site to the SH3 domain. Unlike most other Src members Src lacks cysteine residues in the SH4 domain that undergo palmitylation. Serine and threonine phosphorylation sites have also been identified in the unique domains of Src and are believed to modulate protein-protein interactions or regulate catalytic activity. Alternatively spliced forms of Src, which contain 6- or 11-amino acid insertions in the SH3 domain, are expressed in CNS neurons. c-Src has a unique N-terminal domain, an SH3 domain, an SH2 domain, a kinase domain and a regulatory tail, as do the other members of the family. In general SH2 domains are involved in signal transduction. They typically bind pTyr-containing ligands via two surface pockets, a pTyr and hydrophobic binding pocket, allowing proteins with SH2 domains to localize to tyrosine phosphorylated sites.


Pssm-ID: 198228  Cd Length: 101  Bit Score: 48.12  E-value: 7.57e-07
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 32455248 624 WNVGSSNRNKAENLLRG--KRDGTFLVRES-SKQGCYACSVV----VDG-EVKHCVINKTATGYGFAEPYNLYSSLKELV 695
Cdd:cd10365   5 WYFGKITRRESERLLLNaeNPRGTFLVRESeTTKGAYCLSVSdfdnAKGlNVKHYKIRKLDSGGFYITSRTQFNSLQQLV 84
                        90
                ....*....|....*
gi 32455248 696 LHYQhtslvQHNDSL 710
Cdd:cd10365  85 AYYS-----KHADGL 94
SH2_SHC cd09925
Src homology 2 (SH2) domain found in SH2 adaptor protein C (SHC); SHC is involved in a wide ...
333-414 7.69e-07

Src homology 2 (SH2) domain found in SH2 adaptor protein C (SHC); SHC is involved in a wide variety of pathways including regulating proliferation, angiogenesis, invasion and metastasis, and bone metabolism. An adapter protein, SHC has been implicated in Ras activation following the stimulation of a number of different receptors, including growth factors [insulin, epidermal growth factor (EGF), nerve growth factor, and platelet derived growth factor (PDGF)], cytokines [interleukins 2, 3, and 5], erythropoietin, and granulocyte/macrophage colony-stimulating factor, and antigens [T-cell and B-cell receptors]. SHC has been shown to bind to tyrosine-phosphorylated receptors, and receptor stimulation leads to tyrosine phosphorylation of SHC. Upon phosphorylation, SHC interacts with another adapter protein, Grb2, which binds to the Ras GTP/GDP exchange factor mSOS which leads to Ras activation. SHC is composed of an N-terminal domain that interacts with proteins containing phosphorylated tyrosines, a (glycine/proline)-rich collagen-homology domain that contains the phosphorylated binding site, and a C-terminal SH2 domain. SH2 has been shown to interact with the tyrosine-phosphorylated receptors of EGF and PDGF and with the tyrosine-phosphorylated C chain of the T-cell receptor, providing one of the mechanisms of T-cell-mediated Ras activation. In general SH2 domains are involved in signal transduction. They typically bind pTyr-containing ligands via two surface pockets, a pTyr and hydrophobic binding pocket, allowing proteins with SH2 domains to localize to tyrosine phosphorylated sites.


Pssm-ID: 198179  Cd Length: 104  Bit Score: 48.11  E-value: 7.69e-07
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 32455248 333 WYWGDISREEVNEKLRdtADGTFLVRDaSTKMHGDYTLTLRKGGNNKLIKIFHRDGKYGFSDpLTFSSVVELINHYRNES 412
Cdd:cd09925   9 WYHGKMSRRDAESLLQ--TDGDFLVRE-STTTPGQYVLTGMQNGQPKHLLLVDPEGVVRTKD-RVFESISHLINYHVTNG 84

                ..
gi 32455248 413 LA 414
Cdd:cd09925  85 LP 86
SH3_SNX9_like cd11763
Src Homology 3 domain of Sorting Nexin 9 and similar proteins; Sorting nexins (SNXs) are Phox ...
7-76 7.89e-07

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: 46.55  E-value: 7.89e-07
                        10        20        30        40        50        60        70
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 32455248   7 QYRALYDYKKEREEDIDLHLGDILTVNKgslvalgfSDGQEarpeeiGWLNGYNeTTGERGDFPGTYVEY 76
Cdd:cd11763   1 KVRALYDFDSQPSGELSLRAGEVLTITR--------QDVGD------GWLEGRN-SRGEVGLFPSSYVEI 55
SH2_N-SH2_PLC_gamma_like cd10341
N-terminal Src homology 2 (N-SH2) domain in Phospholipase C gamma; Phospholipase C gamma is a ...
631-703 9.10e-07

N-terminal Src homology 2 (N-SH2) domain in Phospholipase C gamma; Phospholipase C gamma is a signaling molecule that is recruited to the C-terminal tail of the receptor upon autophosphorylation of a highly conserved tyrosine. PLCgamma is composed of a Pleckstrin homology (PH) domain followed by an elongation factor (EF) domain, 2 catalytic regions of PLC domains that flank 2 tandem SH2 domains (N-SH2, C-SH2), and ending with a SH3 domain and C2 domain. N-SH2 SH2 domain-mediated interactions represent a crucial step in transmembrane signaling by receptor tyrosine kinases. SH2 domains recognize phosphotyrosine (pY) in the context of particular sequence motifs in receptor phosphorylation sites. Both N-SH2 and C-SH2 have a very similar binding affinity to pY. But in growth factor stimulated cells these domains bind to different target proteins. N-SH2 binds to pY containing sites in the C-terminal tails of tyrosine kinases and other receptors. Recently it has been shown that this interaction is mediated by phosphorylation-independent interactions between a secondary binding site found exclusively on the N-SH2 domain and a region of the FGFR1 tyrosine kinase domain. This secondary site on the SH2 cooperates with the canonical pY site to regulate selectivity in mediating a specific cellular process. C-SH2 binds to an intramolecular site on PLCgamma itself which allows it to hydrolyze phosphatidylinositol-4,5-bisphosphate into diacylglycerol and inositol triphosphate. These then activate protein kinase C and release calcium. In general SH2 domains are involved in signal transduction. They typically bind pTyr-containing ligands via two surface pockets, a pTyr and hydrophobic binding pocket, allowing proteins with SH2 domains to localize to tyrosine phosphorylated sites.


Pssm-ID: 199829  Cd Length: 99  Bit Score: 47.73  E-value: 9.10e-07
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 32455248 631 RNKAENLLR---GKRDGTFLVRESSK-QGCYACSVVVDGEVKHCVINKT----ATGYGFAEpYNLYSSLKELVLHYQHTS 702
Cdd:cd10341  15 RDEAEKLLLeycEGGDGTFLVRESETfVGDYTLSFWRNGKVQHCRIRSRqengEKKYYLTD-NLVFDSLYELIDYYRQNP 93

                .
gi 32455248 703 L 703
Cdd:cd10341  94 L 94
SH2_PTK6_Brk cd10358
Src homology 2 domain found in protein-tyrosine kinase-6 (PTK6) which is also known as breast ...
333-415 1.07e-06

Src homology 2 domain found in protein-tyrosine kinase-6 (PTK6) which is also known as breast tumor kinase (Brk); Human protein-tyrosine kinase-6 (PTK6, also known as breast tumor kinase (Brk)) is a member of the non-receptor protein-tyrosine kinase family and is expressed in two-thirds of all breast tumors. PTK6 (9). PTK6 contains a SH3 domain, a SH2 domain, and catalytic domains. For the case of the non-receptor protein-tyrosine kinases, the SH2 domain is typically involved in negative regulation of kinase activity by binding to a phosphorylated tyrosine residue near to the C terminus. The C-terminal sequence of PTK6 (PTSpYENPT where pY is phosphotyrosine) is thought to be a self-ligand for the SH2 domain. The structure of the SH2 domain resembles other SH2 domains except for a centrally located four-stranded antiparallel beta-sheet (strands betaA, betaB, betaC, and betaD). There are also differences in the loop length which might be responsible for PTK6 ligand specificity. There are two possible means of regulation of PTK6: autoinhibitory with the phosphorylation of Tyr playing a role in its negative regulation and autophosphorylation at this site, though it has been shown that PTK6 might phosphorylate signal transduction-associated proteins Sam68 and signal transducing adaptor family member 2 (STAP/BKS) in vivo. In general SH2 domains are involved in signal transduction. They typically bind pTyr-containing ligands via two surface pockets, a pTyr and hydrophobic binding pocket, allowing proteins with SH2 domains to localize to tyrosine phosphorylated sites.


Pssm-ID: 198221  Cd Length: 100  Bit Score: 47.43  E-value: 1.07e-06
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 32455248 333 WYWGDISREEVNEKLR--DTADGTFLVRdASTKMHGDYTLTLRKGGNNKLIKIF-HRDGKYGFSDPLTFSSVVELINHYR 409
Cdd:cd10358   4 WFFGCISRSEAVRRLQaeGNATGAFLIR-VSEKPSADYVLSVRDTQAVRHYKIWrRAGGRLHLNEAVSFLSLPELVNYHR 82

                ....*.
gi 32455248 410 NESLAQ 415
Cdd:cd10358  83 AQSLSH 88
SH2_a2chimerin_b2chimerin cd10352
Src homology 2 (SH2) domain found in alpha2-chimerin and beta2-chimerin proteins; Chimerins ...
334-405 1.36e-06

Src homology 2 (SH2) domain found in alpha2-chimerin and beta2-chimerin proteins; Chimerins are a family of phorbol ester- and diacylglycerol-responsive GTPase-activating proteins. Alpha1-chimerin (formerly known as n-chimerin) and alpha2-chimerin are alternatively spliced products of a single gene, as are beta1- and beta2-chimerin. alpha1- and beta1-chimerin have a relatively short N-terminal region that does not encode any recognizable domains, whereas alpha2- and beta2-chimerin both include a functional SH2 domain that can bind to phosphotyrosine motifs within receptors. All of the isoforms contain a GAP domain with specificity in vitro for Rac1 and a diacylglycerol (DAG)-binding C1 domain which allows them to translocate to membranes in response to DAG signaling and anchors them in close proximity to activated Rac. Other C1 domain-containing diacylglycerol receptors including: PKC, Munc-13 proteins, phorbol ester binding scaffolding proteins involved in Ca2+-stimulated exocytosis, and RasGRPs, diacylglycerol-activated guanine-nucleotide exchange factors (GEFs) for Ras and Rap1. In general SH2 domains are involved in signal transduction. They typically bind pTyr-containing ligands via two surface pockets, a pTyr and hydrophobic binding pocket, allowing proteins with SH2 domains to localize to tyrosine phosphorylated sites.


Pssm-ID: 198215  Cd Length: 91  Bit Score: 46.97  E-value: 1.36e-06
                        10        20        30        40        50        60        70
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 32455248 334 YWGDISREEVNEKLRDTADGTFLVRDASTKmHGDYTLTLRKGGNNKLIKIFHrDGK--YGFSDPLTFSSVVELI 405
Cdd:cd10352   9 YHGLISREEAEQLLSGASDGSYLIRESSRD-DGYYTLSLRFNGKVKNYKLYY-DGKnhYHYVGEKRFDTIHDLV 80
SH2_SLAP cd10344
Src homology 2 domain found in Src-like adaptor proteins; SLAP belongs to the subfamily of ...
333-408 1.42e-06

Src homology 2 domain found in Src-like adaptor proteins; SLAP belongs to the subfamily of adapter proteins that negatively regulate cellular signaling initiated by tyrosine kinases. It has a myristylated N-terminus, SH3 and SH2 domains with high homology to Src family tyrosine kinases, and a unique C-terminal tail, which is important for c-Cbl binding. SLAP negatively regulates platelet-derived growth factor (PDGF)-induced mitogenesis in fibroblasts and regulates F-actin assembly for dorsal ruffles formation. c-Cbl mediated SLAP inhibition towards actin remodeling. Moreover, SLAP enhanced PDGF-induced c-Cbl phosphorylation by SFK. In contrast, SLAP mitogenic inhibition was not mediated by c-Cbl, but it rather involved a competitive mechanism with SFK for PDGF-receptor (PDGFR) association and mitogenic signaling. Accordingly, phosphorylation of the Src mitogenic substrates Stat3 and Shc were reduced by SLAP. Thus, we concluded that SLAP regulates PDGFR signaling by two independent mechanisms: a competitive mechanism for PDGF-induced Src mitogenic signaling and a non-competitive mechanism for dorsal ruffles formation mediated by c-Cbl. SLAP is a hematopoietic adaptor containing Src homology (SH)3 and SH2 motifs and a unique carboxy terminus. Unlike c-Src, SLAP lacks a tyrosine kinase domain. Unlike c-Src, SLAP does not impact resorptive function of mature osteoclasts but induces their early apoptosis. SLAP negatively regulates differentiation of osteoclasts and proliferation of their precursors. Conversely, SLAP decreases osteoclast death by inhibiting activation of caspase 3. In general SH2 domains are involved in signal transduction. They typically bind pTyr-containing ligands via two surface pockets, a pTyr and hydrophobic binding pocket, allowing proteins with SH2 domains to localize to tyrosine phosphorylated sites.


Pssm-ID: 198207  Cd Length: 104  Bit Score: 47.10  E-value: 1.42e-06
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 32455248 333 WYWGDISREEVNEKLR--DTADGTFLVRDASTKmHGDYTLTLRKGGNNKLIKIFH------RDGKYGFSDPLTFSSVVEL 404
Cdd:cd10344  12 WLFEGLSREKAEELLMlpGNQVGSFLIRESETR-RGCYSLSVRHRGSQSRDSVKHyrifrlDNGWFYISPRLTFQCLEDM 90

                ....
gi 32455248 405 INHY 408
Cdd:cd10344  91 VNHY 94
SH2_Src_Fgr cd10367
Src homology 2 (SH2) domain found in Gardner-Rasheed feline sarcoma viral (v-fgr) oncogene ...
329-408 1.58e-06

Src homology 2 (SH2) domain found in Gardner-Rasheed feline sarcoma viral (v-fgr) oncogene homolog, Fgr; Fgr is a member of the Src non-receptor type tyrosine kinase family of proteins. The protein contains N-terminal sites for myristoylation and palmitoylation, a PTK domain, and SH2 and SH3 domains which are involved in mediating protein-protein interactions with phosphotyrosine-containing and proline-rich motifs, respectively. Fgr is expressed in B-cells and myeloid cells, localizes to plasma membrane ruffles, and functions as a negative regulator of cell migration and adhesion triggered by the beta-2 integrin signal transduction pathway. Multiple alternatively spliced variants, encoding the same protein, have been identified Fgr has been shown to interact with Wiskott-Aldrich syndrome protein. Fgr has a unique N-terminal domain, an SH3 domain, an SH2 domain, a kinase domain and a regulatory tail, as do the other members of the family. In general SH2 domains are involved in signal transduction. They typically bind pTyr-containing ligands via two surface pockets, a pTyr and hydrophobic binding pocket, allowing proteins with SH2 domains to localize to tyrosine phosphorylated sites.


Pssm-ID: 198230  Cd Length: 101  Bit Score: 47.21  E-value: 1.58e-06
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 32455248 329 QDAEWYWGDISREEVNEKLRDTAD--GTFLVRDASTkMHGDYTLTLR-----KGGNNKLIKIFHRD-GKYGFSDPLTFSS 400
Cdd:cd10367   1 QAEEWYFGKIGRKDAERQLLSPGNprGAFLIRESET-TKGAYSLSIRdwdqnRGDHVKHYKIRKLDtGGYYITTRAQFDT 79

                ....*...
gi 32455248 401 VVELINHY 408
Cdd:cd10367  80 VQELVQHY 87
SH2_SHIP cd10343
Src homology 2 (SH2) domain found in SH2-containing inositol-5'-phosphatase (SHIP) and ...
624-718 1.64e-06

Src homology 2 (SH2) domain found in SH2-containing inositol-5'-phosphatase (SHIP) and SLAM-associated protein (SAP); The SH2-containing inositol-5'-phosphatase, SHIP (also called SHIP1/SHIP1a), is a hematopoietic-restricted phosphatidylinositide phosphatase that translocates to the plasma membrane after extracellular stimulation and hydrolyzes the phosphatidylinositol-3-kinase (PI3K)-generated second messenger PI-3,4,5-P3 (PIP3) to PI-3,4-P2. As a result, SHIP dampens down PIP3 mediated signaling and represses the proliferation, differentiation, survival, activation, and migration of hematopoietic cells. PIP3 recruits lipid-binding pleckstrin homology(PH) domain-containing proteins to the inner wall of the plasma membrane and activates them. PH domain-containing downstream effectors include the survival/proliferation enhancing serine/threonine kinase, Akt (protein kinase B), the tyrosine kinase, Btk, the regulator of protein translation, S6K, and the Rac and cdc42 guanine nucleotide exchange factor, Vav. SHIP is believed to act as a tumor suppressor during leukemogenesis and lymphomagenesis, and may play a role in activating the immune system to combat cancer. SHIP contains an N-terminal SH2 domain, a centrally located phosphatase domain that specifically hydrolyzes the 5'-phosphate from PIP3, PI-4,5-P2 and inositol-1,3,4,5- tetrakisphosphate (IP4), a C2 domain, that is an allosteric activating site when bound by SHIP's enzymatic product, PI-3,4-P2; 2 NPXY motifs that bind proteins with a phosphotyrosine binding (Shc, Dok 1, Dok 2) or an SH2 (p85a, SHIP2) domain; and a proline-rich domain consisting of four PxxP motifs that bind a subset of SH3-containing proteins including Grb2, Src, Lyn, Hck, Abl, PLCg1, and PIAS1. The SH2 domain of SHIP binds to the tyrosine phosphorylated forms of Shc, SHP-2, Doks, Gabs, CD150, platelet-endothelial cell adhesion molecule, Cas, c-Cbl, immunoreceptor tyrosine-based inhibitory motifs (ITIMs), and immunoreceptor tyrosine-based activation motifs (ITAMs). The X-linked lymphoproliferative syndrome (XLP) gene encodes SAP (also called SH2D1A/DSHP) a protein that consists of a 5 residue N-terminus, a single SH2 domain, and a short 25 residue C-terminal tail. XLP is characterized by an extreme sensitivity to Epstein-Barr virus. Both T and natural killer (NK) cell dysfunctions have been seen in XLP patients. SAP binds the cytoplasmic tail of Signaling lymphocytic activation molecule (SLAM), 2B4, Ly-9, and CD84. SAP is believed to function as a signaling inhibitor, by blocking or regulating binding of other signaling proteins. SAP and the SAP-like protein EAT-2 recognize the sequence motif TIpYXX(V/I), which is found in the cytoplasmic domains of a restricted number of T, B, and NK cell surface receptors and are proposed to be natural inhibitors or regulators of the physiological role of a small family of receptors on the surface of these cells. In general SH2 domains are involved in signal transduction. They typically bind pTyr-containing ligands via two surface pockets, a pTyr and hydrophobic binding pocket, allowing proteins with SH2 domains to localize to tyrosine phosphorylated sites.


Pssm-ID: 198206  Cd Length: 103  Bit Score: 47.05  E-value: 1.64e-06
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 32455248 624 WNVGSSNRNKAENLL-RGKRDGTFLVRES-SKQGCYACSVVV-----------DGEVKHCVinKTATGYgfaePYNLYSS 690
Cdd:cd10343   5 WYHGNITRSKAEELLsKAGKDGSFLVRDSeSVSGAYALCVLYqncvhtyrilpNAEDKLSV--QASEGV----PVRFFTT 78
                        90       100
                ....*....|....*....|....*...
gi 32455248 691 LKELVLHYQhtslvQHNDSLNVTLAYPV 718
Cdd:cd10343  79 LPELIEFYQ-----KENMGLVTHLLYPV 101
SH2_Src_Fyn_isoform_a_like cd10418
Src homology 2 (SH2) domain found in Fyn isoform a like proteins; Fyn is a member of the Src ...
329-408 1.74e-06

Src homology 2 (SH2) domain found in Fyn isoform a like proteins; Fyn is a member of the Src non-receptor type tyrosine kinase family of proteins. This cd contains the SH2 domain found in Fyn isoform a type proteins. Fyn is involved in the control of cell growth and is required in the following pathways: T and B cell receptor signaling, integrin-mediated signaling, growth factor and cytokine receptor signaling, platelet activation, ion channel function, cell adhesion, axon guidance, fertilization, entry into mitosis, and differentiation of natural killer cells, oligodendrocytes and keratinocytes. The protein associates with the p85 subunit of phosphatidylinositol 3-kinase and interacts with the Fyn-binding protein. Alternatively spliced transcript variants encoding distinct isoforms exist. Fyn is primarily localized to the cytoplasmic leaflet of the plasma membrane. Tyrosine phosphorylation of target proteins by Fyn serves to either regulate target protein activity, and/or to generate a binding site on the target protein that recruits other signaling molecules. FYN has been shown to interact with a number of proteins including: BCAR1, Cbl, Janus kinase, nephrin, Sky, tyrosine kinase, Wiskott-Aldrich syndrome protein, and Zap-70. Fyn has a unique N-terminal domain, an SH3 domain, an SH2 domain, a kinase domain and a regulatory tail, as do the other members of the family. In general SH2 domains are involved in signal transduction. They typically bind pTyr-containing ligands via two surface pockets, a pTyr and hydrophobic binding pocket, allowing proteins with SH2 domains to localize to tyrosine phosphorylated sites.


Pssm-ID: 198281  Cd Length: 101  Bit Score: 46.92  E-value: 1.74e-06
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 32455248 329 QDAEWYWGDISREEVNEKLRDTAD--GTFLVRDASTkMHGDYTLTLR-----KGGNNKLIKIFHRD-GKYGFSDPLTFSS 400
Cdd:cd10418   1 QAEEWYFGKLGRKDAERQLLSFGNprGTFLIRESET-TKGAYSLSIRdwddmKGDHVKHYKIRKLDnGGYYITTRAQFET 79

                ....*...
gi 32455248 401 VVELINHY 408
Cdd:cd10418  80 LQQLVQHY 87
SH2_ShkD_ShkE cd10357
Src homology 2 (SH2) domain found in SH2 domain-bearing protein kinases D and E (ShkD and ShkE) ...
322-396 1.88e-06

Src homology 2 (SH2) domain found in SH2 domain-bearing protein kinases D and E (ShkD and ShkE); SH2-bearing genes cloned from Dictyostelium include two transcription factors, STATa and STATc, and a signaling factor, SHK1 (shkA). A database search of the Dictyostelium discoideum genome revealed two additional putative STAT sequences, dd-STATb and dd-STATd, and four additional putative SHK genes, dd-SHK2 (shkB), dd-SHK3 (shkC), dd-SHK4 (shkD), and dd-SHK5 (shkE). This model contains members of shkD and shkE. All of the SHK members are most closely related to the protein kinases found in plants. However these kinases in plants are not conjugated to any SH2 or SH2-like sequences. Alignment data indicates that the SHK SH2 domains carry some features of the STAT SH2 domains in Dictyostelium. When STATc's linker domain was used for a BLAST search, the sequence between the protein kinase domain and the SH2 domain (the linker) of SHK was recovered, suggesting a close relationship among these molecules within this region. SHK's linker domain is predicted to contain an alpha-helix which is indeed homologous to that of STAT. Based on the phylogenetic alignment, SH2 domains can be grouped into two categories, STAT-type and Src-type. SHK family members are in between, but are closer to the STAT-type which indicates a close relationship between SHK and STAT families in their SH2 domains and further supports the notion that SHKs linker-SH2 domain evolved from STAT or STATL (STAT-like Linker-SH2) domain found in plants. In SHK, STAT, and SPT6, the linker-SH2 domains all reside exclusively in the C-terminal regions. In general SH2 domains are involved in signal transduction. They typically bind pTyr-containing ligands via two surface pockets, a pTyr and hydrophobic binding pocket, allowing proteins with SH2 domains to localize to tyrosine phosphorylated sites.


Pssm-ID: 198220  Cd Length: 87  Bit Score: 46.35  E-value: 1.88e-06
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 32455248 322 MNNNMSLQDAEWYWGDISREEVNEKLRDTADGTFLVRDASTK-MHGDYTLTLRKGGNNKLIKIFHRD----------GKY 390
Cdd:cd10357   1 IMNINILLAKSWFHGDISRDEAEKRLRGRPEGTFLIRLSSTDpKKTPFTISKKKKSKPVHKRISRIDvnnytsfkipGGY 80

                ....*.
gi 32455248 391 GFSDPL 396
Cdd:cd10357  81 AVSVPL 86
SH2_ShkA_ShkC cd10356
Src homology 2 (SH2) domain found in SH2 domain-bearing protein kinases A and C (ShkA and ShkC) ...
621-695 2.24e-06

Src homology 2 (SH2) domain found in SH2 domain-bearing protein kinases A and C (ShkA and ShkC); SH2-bearing genes cloned from Dictyostelium include two transcription factors, STATa and STATc, and a signaling factor, SHK1 (shkA). A database search of the Dictyostelium discoideum genome revealed two additional putative STAT sequences, dd-STATb and dd-STATd, and four additional putative SHK genes, dd-SHK2 (shkB), dd-SHK3 (shkC), dd-SHK4 (shkD), and dd-SHK5 (shkE). This model contains members of shkA and shkC. All of the SHK members are most closely related to the protein kinases found in plants. However these kinases in plants are not conjugated to any SH2 or SH2-like sequences. Alignment data indicates that the SHK SH2 domains carry some features of the STAT SH2 domains in Dictyostelium. When STATc's linker domain was used for a BLAST search, the sequence between the protein kinase domain and the SH2 domain (the linker) of SHK was recovered, suggesting a close relationship among these molecules within this region. SHK's linker domain is predicted to contain an alpha-helix which is indeed homologous to that of STAT. Based on the phylogenetic alignment, SH2 domains can be grouped into two categories, STAT-type and Src-type. SHK family members are in between, but are closer to the STAT-type which indicates a close relationship between SHK and STAT families in their SH2 domains and further supports the notion that SHKs linker-SH2 domain evolved from STAT or STATL (STAT-like Linker-SH2) domain found in plants. In SHK, STAT, and SPT6, the linker-SH2 domains all reside exclusively in the C-terminal regions. In general SH2 domains are involved in signal transduction. They typically bind pTyr-containing ligands via two surface pockets, a pTyr and hydrophobic binding pocket, allowing proteins with SH2 domains to localize to tyrosine phosphorylated sites.


Pssm-ID: 198219  Cd Length: 113  Bit Score: 46.83  E-value: 2.24e-06
                        10        20        30        40        50        60        70
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 32455248 621 EKTWNVGSSNRNKAENLLRGKRDGTFLVR-ESSKQGCYACSVVVD-GEVKHCVINKtaTGYGFAEPYNLYSSLKELV 695
Cdd:cd10356   9 ECAWFHGDISTSESENRLNGKPEGTFLVRfSTSEPGAYTISKVSKnGGISHQRIHR--PGGKFQVNNSKYLSVKELI 83
RhoGap_RalBP1 cd04381
RhoGap_RalBP1: RhoGAP (GTPase-activator protein [GAP] for Rho-like small GTPases) domain ...
130-272 2.37e-06

RhoGap_RalBP1: RhoGAP (GTPase-activator protein [GAP] for Rho-like small GTPases) domain present in RalBP1 proteins, also known as RLIP, RLIP76 or cytocentrin. RalBP1 plays an important role in endocytosis during interphase. During mitosis, RalBP1 transiently associates with the centromere and has been shown to play an essential role in the proper assembly of the mitotic apparatus. RalBP1 is an effector of the Ral GTPase which itself is an effector of Ras. RalBP1 contains a RhoGAP domain, which shows weak activity towards Rac1 and Cdc42, but not towards Ral, and a Ral effector domain binding motif. Small GTPases cluster into distinct families, and all act as molecular switches, active in their GTP-bound form but inactive when GDP-bound. The Rho family of GTPases activates effectors involved in a wide variety of developmental processes, including regulation of cytoskeleton formation, cell proliferation and the JNK signaling pathway. GTPases generally have a low intrinsic GTPase hydrolytic activity but there are family-specific groups of GAPs that enhance the rate of GTP hydrolysis by several orders of magnitude.


Pssm-ID: 239846 [Multi-domain]  Cd Length: 182  Bit Score: 48.59  E-value: 2.37e-06
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 32455248 130 PLLIK-LVEAIEKKGLECSTLYRTQS-SSNLAELRQLLDcDTPSVDLEMIDVHVLADAFKRYLLDLPNPVIPA---AVYS 204
Cdd:cd04381  21 PLVFReCIDYVEKHGMKCEGIYKVSGiKSKVDELKAAYN-RRESPNLEEYEPPTVASLLKQYLRELPEPLLTKelmPRFE 99
                        90       100       110       120       130       140
                ....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 32455248 205 EMISLAPEVQSSEEYIQLLKKLirspsiPHQYWLTLQYLLKHFFKLSQTSSKNLLNARVLSEIFSPML 272
Cdd:cd04381 100 EACGRPTEAEREQELQRLLKEL------PECNRLLLAWLIVHMDHVIAQELETKMNIQNISIVLSPTV 161
SH2_Tec_Itk cd10396
Src homology 2 (SH2) domain found in Tec protein, IL2-inducible T-cell kinase (Itk); A member ...
624-718 2.37e-06

Src homology 2 (SH2) domain found in Tec protein, IL2-inducible T-cell kinase (Itk); A member of the Tec protein tyrosine kinase Itk is expressed thymus, spleen, lymph node, T lymphocytes, NK and mast cells. It plays a role in T-cell proliferation and differentiation, analogous to Tec family kinases Txk. Itk has been shown to interact with Fyn, Wiskott-Aldrich syndrome protein, KHDRBS1, PLCG1, Lymphocyte cytosolic protein 2, Linker of activated T cells, Karyopherin alpha 2, Grb2, and Peptidylprolyl isomerase A. Most of the Tec family members have a PH domain (Txk and the short (type 1) splice variant of Drosophila Btk29A are exceptions), a Tec homology (TH) domain, a SH3 domain, a SH2 domain, and a protein kinase catalytic domain. The TH domain consists of a Zn2+-binding Btk motif and a proline-rich region. The Btk motif is found in Tec kinases, Ras GAP, and IGBP. It is crucial for the function of Tec PH domains and it's lack of presence in Txk is not surprising since it lacks a PH domain. The type 1 splice form of the Drosophila homolog also lacks both the PH domain and the Btk motif. The proline-rich regions are highly conserved for the most part with the exception of Bmx whose residues surrounding the PXXP motif are not conserved (TH-like) and Btk29A which is entirely unique with large numbers of glycine residues (TH-extended). Tec family members all lack a C-terminal tyrosine having an autoinhibitory function in its phosphorylated state. In general SH2 domains are involved in signal transduction. They typically bind pTyr-containing ligands via two surface pockets, a pTyr and hydrophobic binding pocket, allowing proteins with SH2 domains to localize to tyrosine phosphorylated sites.


Pssm-ID: 198259  Cd Length: 108  Bit Score: 46.71  E-value: 2.37e-06
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 32455248 624 WNVGSSNRNKAENLLRGK-RDGTFLVRESSKQGCYACSV----VVDGE--VKHCVINKTATG---YGFAEPYnLYSSLKE 693
Cdd:cd10396   8 WYNKNINRSKAEKLLRDEgKEGGFMVRDSSQPGLYTVSLytkaGGEGNpcIRHYHIKETNDSpkkYYLAEKH-VFNSIPE 86
                        90       100
                ....*....|....*....|....*
gi 32455248 694 LVLHYQHTSLVqhndsLNVTLAYPV 718
Cdd:cd10396  87 LIEYHKHNAAG-----LVTRLRYPV 106
SH2_a2chimerin_b2chimerin cd10352
Src homology 2 (SH2) domain found in alpha2-chimerin and beta2-chimerin proteins; Chimerins ...
627-669 2.61e-06

Src homology 2 (SH2) domain found in alpha2-chimerin and beta2-chimerin proteins; Chimerins are a family of phorbol ester- and diacylglycerol-responsive GTPase-activating proteins. Alpha1-chimerin (formerly known as n-chimerin) and alpha2-chimerin are alternatively spliced products of a single gene, as are beta1- and beta2-chimerin. alpha1- and beta1-chimerin have a relatively short N-terminal region that does not encode any recognizable domains, whereas alpha2- and beta2-chimerin both include a functional SH2 domain that can bind to phosphotyrosine motifs within receptors. All of the isoforms contain a GAP domain with specificity in vitro for Rac1 and a diacylglycerol (DAG)-binding C1 domain which allows them to translocate to membranes in response to DAG signaling and anchors them in close proximity to activated Rac. Other C1 domain-containing diacylglycerol receptors including: PKC, Munc-13 proteins, phorbol ester binding scaffolding proteins involved in Ca2+-stimulated exocytosis, and RasGRPs, diacylglycerol-activated guanine-nucleotide exchange factors (GEFs) for Ras and Rap1. In general SH2 domains are involved in signal transduction. They typically bind pTyr-containing ligands via two surface pockets, a pTyr and hydrophobic binding pocket, allowing proteins with SH2 domains to localize to tyrosine phosphorylated sites.


Pssm-ID: 198215  Cd Length: 91  Bit Score: 46.20  E-value: 2.61e-06
                        10        20        30        40
                ....*....|....*....|....*....|....*....|....
gi 32455248 627 GSSNRNKAENLLRGKRDGTFLVRESSKQ-GCYACSVVVDGEVKH 669
Cdd:cd10352  11 GLISREEAEQLLSGASDGSYLIRESSRDdGYYTLSLRFNGKVKN 54
SH3_Sorbs_3 cd11780
Third (or C-terminal) Src Homology 3 domain of Sorbin and SH3 domain containing (Sorbs) ...
8-75 2.87e-06

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: 44.98  E-value: 2.87e-06
                        10        20        30        40        50        60        70
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|.
gi 32455248   8 YRALYDYKKEREEDIDLHLGDILTVnkgslvalgfsdgqearpEEI---GWLNGYNETTGERGDFPGTYVE 75
Cdd:cd11780   2 YRALYSYTPQNEDELELREGDIVYV------------------MEKcddGWFVGTSERTGLFGTFPGNYVA 54
SH3 cd00174
Src Homology 3 domain superfamily; Src Homology 3 (SH3) domains are protein interaction ...
7-73 3.56e-06

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: 44.38  E-value: 3.56e-06
                        10        20        30        40        50        60
                ....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 32455248   7 QYRALYDYKKEREEDIDLHLGDILTVnkgslvaLGFSDGqearpeeiGWLNGYNEtTGERGDFPGTY 73
Cdd:cd00174   1 YARALYDYEAQDDDELSFKKGDIITV-------LEKDDD--------GWWEGELN-GGREGLFPANY 51
SH3_Nebulin_family_C cd11789
C-terminal Src Homology 3 domain of the Nebulin family of proteins; Nebulin family proteins ...
7-75 3.74e-06

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: 3.74e-06
                        10        20        30        40        50        60        70
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|.
gi 32455248   7 QYRALYDYKKEREEDIDLHLGDILTvnkgslvalgfsdgqeaRPEEI--GWLNGYNETTGERGDFPGTYVE 75
Cdd:cd11789   1 RYRAMYDYAAADDDEVSFQEGDVII-----------------NVEIIddGWMEGTVQRTGQSGMLPANYVE 54
RhoGAP_fSAC7_BAG7 cd04396
RhoGAP_fSAC7_BAG7: RhoGAP (GTPase-activator protein [GAP] for Rho-like small GTPases) domain ...
142-294 3.84e-06

RhoGAP_fSAC7_BAG7: RhoGAP (GTPase-activator protein [GAP] for Rho-like small GTPases) domain of fungal SAC7 and BAG7-like proteins. Both proteins are GTPase activating proteins of Rho1, but differ functionally in vivo: SAC7, but not BAG7, is involved in the control of Rho1-mediated activation of the PKC-MPK1 pathway. Small GTPases cluster into distinct families, and all act as molecular switches, active in their GTP-bound form but inactive when GDP-bound. The Rho family of GTPases activates effectors involved in a wide variety of developmental processes, including regulation of cytoskeleton formation, cell proliferation and the JNK signaling pathway. GTPases generally have a low intrinsic GTPase hydrolytic activity but there are family-specific groups of GAPs that enhance the rate of GTP hydrolysis by several orders of magnitude.


Pssm-ID: 239861  Cd Length: 225  Bit Score: 48.56  E-value: 3.84e-06
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 32455248 142 KGLECSTLYRTQSSSN-LAELRQLLDcdTP-----SVDLEMIDVHVLADAFKRYLLDLPNPVIPAAVYSEM--------- 206
Cdd:cd04396  46 NATEVEGIFRVAGSSKrIRELQLIFS--TPpdygkSFDWDGYTVHDAASVLRRYLNNLPEPLVPLDLYEEFrnplrkrpr 123
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 32455248 207 -------ISLAPEVQSSEEYIQLLKKLIRSPSIPHQYwLTLqYLLKHFFKLSQTSSKNLLNARVLSEIFSP-MLFRFS-A 277
Cdd:cd04396 124 ilqymkgRINEPLNTDIDQAIKEYRDLITRLPNLNRQ-LLL-YLLDLLAVFARNSDKNLMTASNLAAIFQPgILSHPDhE 201
                       170
                ....*....|....*..
gi 32455248 278 ASSDNTENLIKVIEILI 294
Cdd:cd04396 202 MDPKEYKLSRLVVEFLI 218
SH3_Vinexin_3 cd11918
Third (or C-terminal) Src Homology 3 domain of Vinexin, also called Sorbin and SH3 domain ...
8-74 3.90e-06

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: 3.90e-06
                        10        20        30        40        50        60
                ....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 32455248   8 YRALYDYKKEREEDIDLHLGDILTVNKGSlvalgfsdgqearpeEIGWLNGYNETTGERGDFPGTYV 74
Cdd:cd11918   4 YKAVYQYRPQNEDELELREGDRVDVMQQC---------------DDGWFVGVSRRTQKFGTFPGNYV 55
SH3_Nostrin cd11823
Src homology 3 domain of Nitric Oxide Synthase TRaffic INducer; Nostrin is expressed in ...
7-75 4.17e-06

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: 44.26  E-value: 4.17e-06
                        10        20        30        40        50        60
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 32455248   7 QYRALYDYKKEREEDIDLHLGDILTVNkgslvalgfsdgqeaRPEEIGWLNGynETTGERGDFPGTYVE 75
Cdd:cd11823   1 RCKALYSYTANREDELSLQPGDIIEVH---------------EKQDDGWWLG--ELNGKKGIFPATYVE 52
SH2_Src_Src42 cd10370
Src homology 2 (SH2) domain found in the Src oncogene at 42A (Src42); Src42 is a member of the ...
620-717 4.40e-06

Src homology 2 (SH2) domain found in the Src oncogene at 42A (Src42); Src42 is a member of the Src non-receptor type tyrosine kinase family of proteins. The integration of receptor tyrosine kinase-induced RAS and Src42 signals by Connector eNhancer of KSR (CNK) as a two-component input is essential for RAF activation in Drosophila. Src42 is present in a wide variety of organisms including: California sea hare, pea aphid, yellow fever mosquito, honey bee, Panamanian leafcutter ant, and sea urchin. Src42 has a unique N-terminal domain, an SH3 domain, an SH2 domain, a kinase domain and a regulatory tail, as do the other members of the family. Like the other members of the Src family the SH2 domain in addition to binding the target, also plays an autoinhibitory role by binding to its C-terminal tail. In general SH2 domains are involved in signal transduction. They typically bind pTyr-containing ligands via two surface pockets, a pTyr and hydrophobic binding pocket, allowing proteins with SH2 domains to localize to tyrosine phosphorylated sites.


Pssm-ID: 198233  Cd Length: 96  Bit Score: 45.57  E-value: 4.40e-06
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 32455248 620 DEKTWNVGSSNRNKAEN--LLRGKRDGTFLVRES-SKQGCYACSVVVDGEVKHCVINKTATGYGFAEPYNLYSSLKELVL 696
Cdd:cd10370   1 EAEPWYFGKIKRIEAEKklLLPENEHGAFLIRDSeSRHNDYSLSVRDGDTVKHYRIRQLDEGGFFIARRTTFRTLQELVE 80
                        90       100
                ....*....|....*....|.
gi 32455248 697 HYQHTSlvqhnDSLNVTLAYP 717
Cdd:cd10370  81 HYSKDS-----DGLCVNLRKP 96
SH2_Src_HCK cd10363
Src homology 2 (SH2) domain found in HCK; HCK is a member of the Src non-receptor type ...
624-717 4.51e-06

Src homology 2 (SH2) domain found in HCK; HCK is a member of the Src non-receptor type tyrosine kinase family of proteins and is expressed in hemopoietic cells. HCK is proposed to couple the Fc receptor to the activation of the respiratory burst. It may also play a role in neutrophil migration and in the degranulation of neutrophils. It has two different translational starts that have different subcellular localization. HCK has been shown to interact with BCR gene, ELMO1 Cbl gene, RAS p21 protein activator 1, RASA3, Granulocyte colony-stimulating factor receptor, ADAM15 and RAPGEF1. Like the other members of the Src family the SH2 domain in addition to binding the target, also plays an autoinhibitory role by binding to its C-terminal tail. In general SH2 domains are involved in signal transduction. HCK has a unique N-terminal domain, an SH3 domain, an SH2 domain, a kinase domain and a regulatory tail, as do the other members of the family. They typically bind pTyr-containing ligands via two surface pockets, a pTyr and hydrophobic binding pocket, allowing proteins with SH2 domains to localize to tyrosine phosphorylated sites.


Pssm-ID: 198226  Cd Length: 104  Bit Score: 45.73  E-value: 4.51e-06
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 32455248 624 WNVGSSNRNKAEN--LLRGKRDGTFLVRES-SKQGCYACSV-----VVDGEVKHCVINKTATGYGFAEPYNLYSSLKELV 695
Cdd:cd10363   5 WFFKGISRKDAERqlLAPGNMLGSFMIRDSeTTKGSYSLSVrdydpQHGDTVKHYKIRTLDNGGFYISPRSTFSTLQELV 84
                        90       100
                ....*....|....*....|..
gi 32455248 696 LHYQhtslvQHNDSLNVTLAYP 717
Cdd:cd10363  85 DHYK-----KGNDGLCQKLSVP 101
RhoGAP_fBEM3 cd04400
RhoGAP_fBEM3: RhoGAP (GTPase-activator [GAP] protein for Rho-like small GTPases) domain of ...
172-272 4.52e-06

RhoGAP_fBEM3: RhoGAP (GTPase-activator [GAP] protein for Rho-like small GTPases) domain of fungal BEM3-like proteins. Bem3 is a GAP protein of Cdc42, and is specifically involved in the control of the initial assembly of the septin ring in yeast bud formation. Small GTPases cluster into distinct families, and all act as molecular switches, active in their GTP-bound form but inactive when GDP-bound. The Rho family of GTPases activates effectors involved in a wide variety of developmental processes, including regulation of cytoskeleton formation, cell proliferation and the JNK signaling pathway. GTPases generally have a low intrinsic GTPase hydrolytic activity but there are family-specific groups of GAPs that enhance the rate of GTP hydrolysis by several orders of magnitude.


Pssm-ID: 239865 [Multi-domain]  Cd Length: 190  Bit Score: 47.74  E-value: 4.52e-06
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 32455248 172 VDL----EMIDVHVLADAFKRYLLDLPNPVIPAAVYSEMISLAPEVQSSEEYIQLLKKLIRspSIPHQYWLTLQYLLKHF 247
Cdd:cd04400  67 VDLfsssLYPDVHTVAGLLKLYLRELPTLILGGELHNDFKRLVEENHDRSQRALELKDLVS--QLPQANYDLLYVLFSFL 144
                        90       100
                ....*....|....*....|....*
gi 32455248 248 FKLSQTSSKNLLNARVLSEIFSPML 272
Cdd:cd04400 145 RKIIEHSDVNKMNLRNVCIVFSPTL 169
SH3_Nebulette_C cd11935
C-terminal Src Homology 3 domain of Nebulette and LIM-nebulette (or Lasp2); Nebulette is a ...
8-77 5.88e-06

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: 44.22  E-value: 5.88e-06
                        10        20        30        40        50        60        70
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 32455248   8 YRALYDYKKEREEDIDLHLGDILtvnkgslvalgfsdgQEARPEEIGWLNGYNETTGERGDFPGTYVEYI 77
Cdd:cd11935   3 YRAMYDYSAQDEDEVSFRDGDYI---------------VNVQPIDEGWMYGTVQRTGRTGMLPANYIEFV 57
SH3_Lasp1_C cd11934
C-terminal Src Homology 3 domain of LIM and SH3 domain protein 1; Lasp1 is a cytoplasmic ...
5-77 7.59e-06

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: 43.83  E-value: 7.59e-06
                        10        20        30        40        50        60        70
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|...
gi 32455248   5 GYQYRALYDYKKEREEDIDLHLGDILTvnkgslvalgfsDGQEArpeEIGWLNGYNETTGERGDFPGTYVEYI 77
Cdd:cd11934   2 GKRYRAVYDYNAADEDEVSFQDGDTIV------------NVQQI---DDGWMYGTVERTGDTGMLPANYVEAI 59
SH3_SH3RF_C cd11785
C-terminal (Fourth) Src Homology 3 domain of SH3 domain containing ring finger 1 (SH3RF1), ...
7-75 7.93e-06

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: 43.61  E-value: 7.93e-06
                        10        20        30        40        50        60
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 32455248   7 QYRALYDYKKEREEDIDLHLGDILTVNKgslvalgfsdgqearPEEIGWLNGYNETTGERGDFPGTYVE 75
Cdd:cd11785   1 RYRVIVPYPPQSEAELELKEGDIVFVHK---------------KREDGWFKGTLQRTGKTGLFPGSFVE 54
SH2_Src_Fyn cd10368
Src homology 2 (SH2) domain found in Fyn; Fyn is a member of the Src non-receptor type ...
329-408 9.03e-06

Src homology 2 (SH2) domain found in Fyn; Fyn is a member of the Src non-receptor type tyrosine kinase family of proteins. Fyn is involved in the control of cell growth and is required in the following pathways: T and B cell receptor signaling, integrin-mediated signaling, growth factor and cytokine receptor signaling, platelet activation, ion channel function, cell adhesion, axon guidance, fertilization, entry into mitosis, and differentiation of natural killer cells, oligodendrocytes and keratinocytes. The protein associates with the p85 subunit of phosphatidylinositol 3-kinase and interacts with the Fyn-binding protein. Alternatively spliced transcript variants encoding distinct isoforms exist. Fyn is primarily localized to the cytoplasmic leaflet of the plasma membrane. Tyrosine phosphorylation of target proteins by Fyn serves to either regulate target protein activity, and/or to generate a binding site on the target protein that recruits other signaling molecules. FYN has been shown to interact with a number of proteins including: BCAR1, Cbl, Janus kinase, nephrin, Sky, tyrosine kinase, Wiskott-Aldrich syndrome protein, and Zap-70. Fyn has a unique N-terminal domain, an SH3 domain, an SH2 domain, a kinase domain and a regulatory tail, as do the other members of the family. In general SH2 domains are involved in signal transduction. They typically bind pTyr-containing ligands via two surface pockets, a pTyr and hydrophobic binding pocket, allowing proteins with SH2 domains to localize to tyrosine phosphorylated sites.


Pssm-ID: 198231 [Multi-domain]  Cd Length: 101  Bit Score: 45.02  E-value: 9.03e-06
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 32455248 329 QDAEWYWGDISREEVNEKLRDTAD--GTFLVRDASTkMHGDYTLTLR-----KGGNNKLIKIFHRD-GKYGFSDPLTFSS 400
Cdd:cd10368   1 QAEEWYFGKLGRKDAERQLLSFGNprGTFLIRESET-TKGAYSLSIRdwddmKGDHVKHYKIRKLDnGGYYITTRAQFET 79

                ....*...
gi 32455248 401 VVELINHY 408
Cdd:cd10368  80 LQQLVQHY 87
SH2_SH2D7 cd10417
Src homology 2 domain found in the SH2 domain containing protein 7 (SH2D7); SH2D7 contains a ...
624-710 9.03e-06

Src homology 2 domain found in the SH2 domain containing protein 7 (SH2D7); SH2D7 contains a single SH2 domain. In general SH2 domains are involved in signal transduction. They typically bind pTyr-containing ligands via two surface pockets, a pTyr and hydrophobic binding pocket, allowing proteins with SH2 domains to localize to tyrosine phosphorylated sites.


Pssm-ID: 199832  Cd Length: 102  Bit Score: 44.88  E-value: 9.03e-06
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 32455248 624 WNVGSSNRNKAENLLRGKRDGTFLVRESSKQGCYACSVVVDGEVKHCVINKTATG-YGFAEPYNLYSSLKELVLHYQHTS 702
Cdd:cd10417   9 WFHGFITRKQTEQLLRDKALGSFLIRLSDRATGYILSYRGSDRCRHFVINQLRNRrYLISGDTSSHSTLAELVRHYQEVQ 88

                ....*...
gi 32455248 703 LVQHNDSL 710
Cdd:cd10417  89 LEPFGETL 96
SH2_BCAR3 cd10337
Src homology 2 (SH2) domain in the Breast Cancer Anti-estrogen Resistance protein 3; BCAR3 is ...
614-699 9.17e-06

Src homology 2 (SH2) domain in the Breast Cancer Anti-estrogen Resistance protein 3; BCAR3 is part of a growing family of guanine nucleotide exchange factors is responsible for activation of Ras-family GTPases, including Sos1 and 2, GRF1 and 2, CalDAG-GEF/GRP1-4, C3G, cAMP-GEF/Epac 1 and 2, PDZ-GEFs, MR-GEF, RalGDS family members, RalGPS, RasGEF, Smg GDS, and phospholipase C(epsilon). 12102558 21262352 BCAR3 binds to the carboxy-terminus of BCAR1/p130Cas, a focal adhesion adapter protein. Over expression of BCAR1 (p130Cas) and BCAR3 induces estrogen independent growth in normally estrogen-dependent cell lines. They have been linked to resistance to anti-estrogens in breast cancer, Rac activation, and cell motility, though the BCAR3/p130Cas complex is not required for this activity in BCAR3. Many BCAR3-mediated signaling events in epithelial and mesenchymal cells are independent of p130Cas association. Structurally these proteins contain a single SH2 domain upstream of their RasGEF domain, which is responsible for the ability of BCAR3 to enhance p130Cas over-expression-induced migration. In general SH2 domains are involved in signal transduction. They typically bind pTyr-containing ligands via two surface pockets, a pTyr and hydrophobic binding pocket, allowing proteins with SH2 domains to localize to tyrosine phosphorylated sites.


Pssm-ID: 198200 [Multi-domain]  Cd Length: 136  Bit Score: 45.79  E-value: 9.17e-06
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 32455248 614 EDLPHHdekTWNVGSSNRNKAENLLRgkRDGTFLVRES-SKQGCYACSVVVDGEVKHCVINKTATGYGFAEPYNLY---- 688
Cdd:cd10337   1 EDLRSH---AWYHGRIPRQVAESLVQ--REGDFLVRDSlSSPGDYVLTCRWKGQPLHFKINRVVLRPSEAYTRVQYqfed 75
                        90
                ....*....|....
gi 32455248 689 ---SSLKELVLHYQ 699
Cdd:cd10337  76 eqfDSIPALVHFYV 89
SH2_Fps_family cd10361
Src homology 2 (SH2) domain found in feline sarcoma, Fujinami poultry sarcoma, and fes-related ...
631-703 1.09e-05

Src homology 2 (SH2) domain found in feline sarcoma, Fujinami poultry sarcoma, and fes-related (Fes/Fps/Fer) proteins; The Fps family consists of members Fps/Fes and Fer/Flk/Tyk3. They are cytoplasmic protein-tyrosine kinases implicated in signaling downstream from cytokines, growth factors and immune receptors. Fes/Fps/Fer contains three coiled-coil regions, an SH2 (Src-homology-2) and a TK (tyrosine kinase catalytic) domain signature. Members here include: Fps/Fes, Fer, Kin-31, and In general SH2 domains are involved in signal transduction. They typically bind pTyr-containing ligands via two surface pockets, a pTyr and hydrophobic binding pocket, allowing proteins with SH2 domains to localize to tyrosine phosphorylated sites.


Pssm-ID: 198224  Cd Length: 90  Bit Score: 44.44  E-value: 1.09e-05
                        10        20        30        40        50        60        70
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 32455248 631 RNKAENLLrgKRDGTFLVRESSKQGC----YACSVVVDGEVKHCVINKTATG-YGFAEpyNLYSSLKELVLHYQHTSL 703
Cdd:cd10361  15 REDAEELL--KNDGDFLVRKTEPKGGgkrkLVLSVRWDGKIRHFVINRDDGGkYYIEG--KSFKSISELINYYQKTKE 88
SH2_BCAR3 cd10337
Src homology 2 (SH2) domain in the Breast Cancer Anti-estrogen Resistance protein 3; BCAR3 is ...
328-408 1.18e-05

Src homology 2 (SH2) domain in the Breast Cancer Anti-estrogen Resistance protein 3; BCAR3 is part of a growing family of guanine nucleotide exchange factors is responsible for activation of Ras-family GTPases, including Sos1 and 2, GRF1 and 2, CalDAG-GEF/GRP1-4, C3G, cAMP-GEF/Epac 1 and 2, PDZ-GEFs, MR-GEF, RalGDS family members, RalGPS, RasGEF, Smg GDS, and phospholipase C(epsilon). 12102558 21262352 BCAR3 binds to the carboxy-terminus of BCAR1/p130Cas, a focal adhesion adapter protein. Over expression of BCAR1 (p130Cas) and BCAR3 induces estrogen independent growth in normally estrogen-dependent cell lines. They have been linked to resistance to anti-estrogens in breast cancer, Rac activation, and cell motility, though the BCAR3/p130Cas complex is not required for this activity in BCAR3. Many BCAR3-mediated signaling events in epithelial and mesenchymal cells are independent of p130Cas association. Structurally these proteins contain a single SH2 domain upstream of their RasGEF domain, which is responsible for the ability of BCAR3 to enhance p130Cas over-expression-induced migration. In general SH2 domains are involved in signal transduction. They typically bind pTyr-containing ligands via two surface pockets, a pTyr and hydrophobic binding pocket, allowing proteins with SH2 domains to localize to tyrosine phosphorylated sites.


Pssm-ID: 198200 [Multi-domain]  Cd Length: 136  Bit Score: 45.40  E-value: 1.18e-05
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 32455248 328 LQDAEWYWGDISREEVNEKLRdtADGTFLVRDASTKMhGDYTLTLRKGGNN---KLIKIFHRDGK------YGFSDPlTF 398
Cdd:cd10337   3 LRSHAWYHGRIPRQVAESLVQ--REGDFLVRDSLSSP-GDYVLTCRWKGQPlhfKINRVVLRPSEaytrvqYQFEDE-QF 78
                        90
                ....*....|
gi 32455248 399 SSVVELINHY 408
Cdd:cd10337  79 DSIPALVHFY 88
SH3_Amphiphysin cd11790
Src Homology 3 domain of Amphiphysin and related domains; Amphiphysins function primarily in ...
6-77 1.20e-05

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: 43.47  E-value: 1.20e-05
                        10        20        30        40        50        60        70
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|..
gi 32455248   6 YQYRALYDYKKEREEDIDLHLGDILTVnkgslvaLGFSDGQEarpEEIGWLNGYNETTGERGDFPGTYVEYI 77
Cdd:cd11790   3 YKVRATHDYTAEDTDELTFEKGDVILV-------IPFDDPEE---QDEGWLMGVKESTGCRGVFPENFTERI 64
SH3_Intersectin1_1 cd11987
First Src homology 3 domain (or SH3A) of Intersectin-1; Intersectin-1 (ITSN1) is an adaptor ...
8-75 1.20e-05

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: 43.06  E-value: 1.20e-05
                        10        20        30        40        50        60
                ....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 32455248   8 YRALYDYKKEREEDIDLHLGDILTVNkgslvalgfsdgqEARPEEIGWLNGynETTGERGDFPGTYVE 75
Cdd:cd11987   2 YRALYPFEARSHDEITIQPGDIVMVD-------------ESQTGEPGWLGG--ELKGKTGWFPANYAE 54
SH2_csk_like cd09937
Src homology 2 (SH2) domain found in Carboxyl-Terminal Src Kinase (Csk); Both the C-terminal ...
624-699 1.36e-05

Src homology 2 (SH2) domain found in Carboxyl-Terminal Src Kinase (Csk); Both the C-terminal Src kinase (CSK) and CSK-homologous kinase (CHK) are members of the CSK-family of protein tyrosine kinases. These proteins suppress activity of Src-family kinases (SFK) by selectively phosphorylating the conserved C-terminal tail regulatory tyrosine by a similar mechanism. CHK is also capable of inhibiting SFKs by a non-catalytic mechanism that involves binding of CHK to SFKs to form stable protein complexes. The unphosphorylated form of SFKs is inhibited by CSK and CHK by a two-step mechanism. The first step involves the formation of a complex of SFKs with CSK/CHK with the SFKs in the complex are inactive. The second step, involves the phosphorylation of the C-terminal tail tyrosine of SFKs, which then dissociates and adopt an inactive conformation. The structural basis of how the phosphorylated SFKs dissociate from CSK/CHK to adopt the inactive conformation is not known. The inactive conformation of SFKs is stabilized by two intramolecular inhibitory interactions: (a) the pYT:SH2 interaction in which the phosphorylated C-terminal tail tyrosine (YT) binds to the SH2 domain, and (b) the linker:SH3 interaction of which the SH2-kinase domain linker binds to the SH3 domain. SFKs are activated by multiple mechanisms including binding of the ligands to the SH2 and SH3 domains to displace the two inhibitory intramolecular interactions, autophosphorylation, and dephosphorylation of YT. By selective phosphorylation and the non-catalytic inhibitory mechanism CSK and CHK are able to inhibit the active forms of SFKs. CSK and CHK are regulated by phosphorylation and inter-domain interactions. They both contain SH3, SH2, and kinase domains separated by the SH3-SH2 connector and SH2 kinase linker, intervening segments separating the three domains. They lack a conserved tyrosine phosphorylation site in the kinase domain and the C-terminal tail regulatory tyrosine phosphorylation site. The CSK SH2 domain is crucial for stabilizing the kinase domain in the active conformation. A disulfide bond here regulates CSK kinase activity. The subcellular localization and activity of CSK are regulated by its SH2 domain. In general SH2 domains are involved in signal transduction. They typically bind pTyr-containing ligands via two surface pockets, a pTyr and hydrophobic binding pocket, allowing proteins with SH2 domains to localize to tyrosine phosphorylated sites.


Pssm-ID: 198190  Cd Length: 98  Bit Score: 44.20  E-value: 1.36e-05
                        10        20        30        40        50        60        70
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 32455248 624 WNVGSSNRNKAENLLRGKRDGTFLVRESSKQ-GCYACSVVVDGEVKHCVINKTATGYGF-AEPYnlYSSLKELVLHYQ 699
Cdd:cd09937   5 WFHGKISREEAERLLQPPEDGLFLVRESTNYpGDYTLCVSFEGKVEHYRVIYRNGKLTIdEEEY--FENLIQLVEHYT 80
SH2_Src_Lck cd10362
Src homology 2 (SH2) domain in lymphocyte cell kinase (Lck); Lck is a member of the Src ...
623-717 1.39e-05

Src homology 2 (SH2) domain in lymphocyte cell kinase (Lck); Lck is a member of the Src non-receptor type tyrosine kinase family of proteins. It is expressed in the brain, T-cells, and NK cells. The unique domain of Lck mediates its interaction with two T-cell surface molecules, CD4 and CD8. It associates with their cytoplasmic tails on CD4 T helper cells and CD8 cytotoxic T cells to assist signaling from the T cell receptor (TCR) complex. When the T cell receptor is engaged by the specific antigen presented by MHC, Lck phosphorylase the intracellular chains of the CD3 and zeta-chains of the TCR complex, allowing ZAP-70 to bind them. Lck then phosphorylates and activates ZAP-70, which in turn phosphorylates Linker of Activated T cells (LAT), a transmembrane protein that serves as a docking site for proteins including: Shc-Grb2-SOS, PI3K, and phospholipase C (PLC). The tyrosine phosphorylation cascade culminates in the intracellular mobilization of a calcium ions and activation of important signaling cascades within the lymphocyte, including the Ras-MEK-ERK pathway, which goes on to activate certain transcription factors such as NFAT, NF-kappaB, and AP-1. These transcription factors regulate the production cytokines such as Interleukin-2 that promote long-term proliferation and differentiation of the activated lymphocytes. The N-terminal tail of Lck is myristoylated and palmitoylated and it tethers the protein to the plasma membrane of the cell. Lck also contains a SH3 domain, a SH2 domain, and a C-terminal tyrosine kinase domain. Lck has 2 phosphorylation sites, the first an autophosphorylation site that is linked to activation of the protein and the second which is phosphorylated by Csk, which inhibits it. Lck is also inhibited by SHP-1 dephosphorylation and by Cbl ubiquitin ligase, which is part of the ubiquitin-mediated pathway. In general SH2 domains are involved in signal transduction. They typically bind pTyr-containing ligands via two surface pockets, a pTyr and hydrophobic binding pocket, allowing proteins with SH2 domains to localize to tyrosine phosphorylated sites.


Pssm-ID: 198225  Cd Length: 101  Bit Score: 44.48  E-value: 1.39e-05
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 32455248 623 TWNVGSSNRNKAE--NLLRGKRDGTFLVRES-SKQGCYACSV----VVDGE-VKHCVINKTATGYGFAEPYNLYSSLKEL 694
Cdd:cd10362   4 PWFFKNLSRNDAErqLLAPGNTHGSFLIRESeTTAGSFSLSVrdfdQNQGEvVKHYKIRNLDNGGFYISPRITFPGLHEL 83
                        90       100
                ....*....|....*....|...
gi 32455248 695 VLHYQHTSlvqhnDSLNVTLAYP 717
Cdd:cd10362  84 VRHYTNAS-----DGLCTRLSRP 101
SH2_N-SH2_Zap70_Syk_like cd09938
N-terminal Src homology 2 (SH2) domain found in Zeta-chain-associated protein kinase 70 ...
624-717 1.63e-05

N-terminal Src homology 2 (SH2) domain found in Zeta-chain-associated protein kinase 70 (ZAP-70) and Spleen tyrosine kinase (Syk) proteins; ZAP-70 and Syk comprise a family of hematopoietic cell specific protein tyrosine kinases (PTKs) that are required for antigen and antibody receptor function. ZAP-70 is expressed in T and natural killer (NK) cells and Syk is expressed in B cells, mast cells, polymorphonuclear leukocytes, platelets, macrophages, and immature T cells. They are required for the proper development of T and B cells, immune receptors, and activating NK cells. They consist of two N-terminal Src homology 2 (SH2) domains and a C-terminal kinase domain separated from the SH2 domains by a linker or hinge region. Phosphorylation of both tyrosine residues within the Immunoreceptor Tyrosine-based Activation Motifs (ITAM; consensus sequence Yxx[LI]x(7,8)Yxx[LI]) by the Src-family PTKs is required for efficient interaction of ZAP-70 and Syk with the receptor subunits and for receptor function. ZAP-70 forms two phosphotyrosine binding pockets, one of which is shared by both SH2 domains. In Syk the two SH2 domains do not form such a phosphotyrosine-binding site. The SH2 domains here are believed to function independently. In addition, the two SH2 domains of Syk display flexibility in their relative orientation, allowing Syk to accommodate a greater variety of spacing sequences between the ITAM phosphotyrosines and singly phosphorylated non-classical ITAM ligands. This model contains the N-terminus SH2 domains of both Syk and Zap70. In general SH2 domains are involved in signal transduction. They typically bind pTyr-containing ligands via two surface pockets, a pTyr and hydrophobic binding pocket, allowing proteins with SH2 domains to localize to tyrosine phosphorylated sites.


Pssm-ID: 198191  Cd Length: 104  Bit Score: 44.31  E-value: 1.63e-05
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 32455248 624 WNVGSSNRNKAENLLR--GKRDGTFLVRES-SKQGCYACSVVVDGEVKHCVINK-------TATGYGFAEPynlysslKE 693
Cdd:cd09938   3 FFYGSITREEAEEYLKlaGMSDGLFLLRQSlRSLGGYVLSVCHGRKFHHYTIERqlngtyaIAGGKAHCGP-------AE 75
                        90       100
                ....*....|....*....|....
gi 32455248 694 LVLHYQHTSlvqhnDSLNVTLAYP 717
Cdd:cd09938  76 LCEYHSTDL-----DGLVCLLRKP 94
SH3_GRAF-like cd11882
Src Homology 3 domain of GTPase Regulator Associated with Focal adhesion kinase and similar ...
9-76 1.63e-05

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: 42.67  E-value: 1.63e-05
                        10        20        30        40        50        60
                ....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 32455248   9 RALYDYKKEREEDIDLHLGDIltvnkgslvalgFSDGQEArpEEIGWLNGYNEttGERGDFPGTYVEY 76
Cdd:cd11882   3 RALYACKAEDESELSFEPGQI------------ITNVQPS--DEPGWLEGTLN--GRTGLIPENYVEF 54
SH2_Tec_Btk cd10397
Src homology 2 (SH2) domain found in Tec protein, Bruton's tyrosine kinase (Btk); A member of ...
327-429 1.92e-05

Src homology 2 (SH2) domain found in Tec protein, Bruton's tyrosine kinase (Btk); A member of the Tec protein tyrosine kinase Btk is expressed in bone marrow, spleen, all hematopoietic cells except T lymphocytes and plasma cells where it plays a crucial role in B cell maturation and mast cell activation. Btk has been shown to interact with GNAQ, PLCG2, protein kinase D1, B-cell linker, SH3BP5, caveolin 1, ARID3A, and GTF2I. Most of the Tec family members have a PH domain (Txk and the short (type 1) splice variant of Drosophila Btk29A are exceptions), a Tec homology (TH) domain, a SH3 domain, a SH2 domain, and a protein kinase catalytic domain. Btk is implicated in the primary immunodeficiency disease X-linked agammaglobulinemia (Bruton's agammaglobulinemia). The TH domain consists of a Zn2+-binding Btk motif and a proline-rich region. The Btk motif is found in Tec kinases, Ras GAP, and IGBP. It is crucial for the function of Tec PH domains and it's lack of presence in Txk is not surprising since it lacks a PH domain. The type 1 splice form of the Drosophila homolog also lacks both the PH domain and the Btk motif. The proline-rich regions are highly conserved for the most part with the exception of Bmx whose residues surrounding the PXXP motif are not conserved (TH-like) and Btk29A which is entirely unique with large numbers of glycine residues (TH-extended). Tec family members all lack a C-terminal tyrosine having an autoinhibitory function in its phosphorylated state. Two tyrosine phosphorylation (pY) sites have been identified in Btk: one located in the activation loop of the catalytic domain which regulates the transition between open (active) and closed (inactive) states and the other in its SH3 domain. In general SH2 domains are involved in signal transduction. They typically bind pTyr-containing ligands via two surface pockets, a pTyr and hydrophobic binding pocket, allowing proteins with SH2 domains to localize to tyrosine phosphorylated sites.


Pssm-ID: 198260 [Multi-domain]  Cd Length: 106  Bit Score: 44.05  E-value: 1.92e-05
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 32455248 327 SLQDAEWYWGDISREEVNEKLR-DTADGTFLVRDASTKmhGDYTLT-LRKGGNNKLIKIFH------RDGKYGFSDPLTF 398
Cdd:cd10397   2 SLEMYEWYSKNMTRSQAEQLLKqEGKEGGFIVRDSSKA--GKYTVSvFAKSAGDPQGVIRHyvvcstPQSQYYLAEKHLF 79
                        90       100       110
                ....*....|....*....|....*....|.
gi 32455248 399 SSVVELINHYRNESLAqynpkLDVKLLYPVS 429
Cdd:cd10397  80 STIPELINYHQHNAAG-----LISRLKYPVS 105
RhoGAP_ARHGAP18 cd04391
RhoGAP_ARHGAP18: RhoGAP (GTPase-activator protein [GAP] for Rho-like small GTPases) domain of ...
124-285 1.92e-05

RhoGAP_ARHGAP18: RhoGAP (GTPase-activator protein [GAP] for Rho-like small GTPases) domain of ArhGAP18-like proteins. The function of ArhGAP18 is unknown. Small GTPases cluster into distinct families, and all act as molecular switches, active in their GTP-bound form but inactive when GDP-bound. The Rho family of GTPases activates effectors involved in a wide variety of developmental processes, including regulation of cytoskeleton formation, cell proliferation and the JNK signaling pathway. GTPases generally have a low intrinsic GTPase hydrolytic activity but there are family-specific groups of GAPs that enhance the rate of GTP hydrolysis by several orders of magnitude.


Pssm-ID: 239856  Cd Length: 216  Bit Score: 46.19  E-value: 1.92e-05
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 32455248 124 PPDIAPPLLI-KLVEAIEKKGLECSTLYRTQ-SSSNLAELRQLLD--CDTPSVDLEMIDVHVLADAFKRYLLDLPNPV-- 197
Cdd:cd04391  17 VPGSKVPLIFqKLINKLEERGLETEGILRIPgSAQRVKFLCQELEakFYEGTFLWDQVKQHDAASLLKLFIRELPQPLlt 96
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 32455248 198 ---IPAAVYSEMISlapevqSSEEYIQLLKKLIRSPSIPHQYwlTLQYLLKHFFKLSQTSSKNLLNARVLSEIFSPMLFR 274
Cdd:cd04391  97 veyLPAFYSVQGLP------SKKDQLQALNLLVLLLPEANRD--TLKALLEFLQKVVDHEEKNKMNLWNVAMIMAPNLFP 168
                       170
                ....*....|..
gi 32455248 275 F-SAASSDNTEN 285
Cdd:cd04391 169 PrGKHSKDNESL 180
SH2_SHE cd10391
Src homology 2 domain found in SH2 domain-containing adapter protein E (SHE); SHE is expressed ...
333-428 2.15e-05

Src homology 2 domain found in SH2 domain-containing adapter protein E (SHE); SHE is expressed in heart, lung, brain, and skeletal muscle. SHE contains two pTry protein binding domains, protein interaction domain (PID) and a SH2 domain, followed by a glycine-proline rich region, all of which are N-terminal to the phosphotyrosine binding (PTB) domain. In general SH2 domains are involved in signal transduction. They typically bind pTyr-containing ligands via two surface pockets, a pTyr and hydrophobic binding pocket, allowing proteins with SH2 domains to localize to tyrosine phosphorylated sites.


Pssm-ID: 198254  Cd Length: 98  Bit Score: 43.79  E-value: 2.15e-05
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 32455248 333 WYWGDISREEVNEKLRDTADGTFLVRDaSTKMHGDYTLTLRKG-GNNKLIKIFHRDGKYGFSD-PLTFSSVVELINHYRN 410
Cdd:cd10391   3 WYHGSISRAEAESRLQPCKEASYLVRN-SESGNSKYSIALKTSqGCVHIIVAQTKDNKYTLNQtSAVFDSIPEVVHYYSN 81
                        90
                ....*....|....*...
gi 32455248 411 ESLAqYNPKLDVKLLYPV 428
Cdd:cd10391  82 EKLP-FKGAEHMTLLHPV 98
SH2_Src_Frk cd10369
Src homology 2 (SH2) domain found in the Fyn-related kinase (Frk); Frk is a member of the Src ...
333-412 2.50e-05

Src homology 2 (SH2) domain found in the Fyn-related kinase (Frk); Frk is a member of the Src non-receptor type tyrosine kinase family of proteins. The Frk subfamily is composed of Frk/Rak and Iyk/Bsk/Gst. It is expressed primarily epithelial cells. Frk is a nuclear protein and may function during G1 and S phase of the cell cycle and suppress growth. Unlike the other Src members it lacks a glycine at position 2 of SH4 which is important for addition of a myristic acid moiety that is involved in targeting Src PTKs to cellular membranes. FRK and SHB exert similar effects when overexpressed in rat phaeochromocytoma (PC12) and beta-cells, where both induce PC12 cell differentiation and beta-cell proliferation. Under conditions that cause beta-cell degeneration these proteins augment beta-cell apoptosis. The FRK-SHB responses involve FAK and insulin receptor substrates (IRS) -1 and -2. Frk has been demonstrated to interact with retinoblastoma protein. Frk regulates PTEN protein stability by phosphorylating PTEN, which in turn prevents PTEN degradation. Frk also plays a role in regulation of embryonal pancreatic beta cell formation. Frk has a unique N-terminal domain, an SH3 domain, an SH2 domain, a kinase domain and a regulatory tail, as do the other members of the family. Like the other members of the Src family the SH2 domain in addition to binding the target, also plays an autoinhibitory role by binding to its activation loop. The tryosine involved is at the same site as the tyrosine involved in the autophosphorylation of Src. In general SH2 domains are involved in signal transduction. They typically bind pTyr-containing ligands via two surface pockets, a pTyr and hydrophobic binding pocket, allowing proteins with SH2 domains to localize to tyrosine phosphorylated sites.


Pssm-ID: 199831  Cd Length: 96  Bit Score: 43.33  E-value: 2.50e-05
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 32455248 333 WYWGDISREEVNEKL--RDTADGTFLVRDaSTKMHGDYTLTLRKGGNNKLIKIFHRD-GKYGFSDPLTFSSVVELINHYR 409
Cdd:cd10369   5 WFFGAIKRADAEKQLlySENQTGAFLIRE-SESQKGEFSLSVLDGGVVKHYRIRRLDeGGFFLTRRKTFSTLNEFVNYYT 83

                ...
gi 32455248 410 NES 412
Cdd:cd10369  84 TTS 86
RhoGAP_fRGD2 cd04399
RhoGAP_fRGD2: RhoGAP (GTPase-activator protein [GAP] for Rho-like small GTPases) domain of ...
161-250 2.62e-05

RhoGAP_fRGD2: RhoGAP (GTPase-activator protein [GAP] for Rho-like small GTPases) domain of fungal RGD2-like proteins. Yeast Rgd2 is a GAP protein for Cdc42 and Rho5. Small GTPases cluster into distinct families, and all act as molecular switches, active in their GTP-bound form but inactive when GDP-bound. The Rho family of GTPases activates effectors involved in a wide variety of developmental processes, including regulation of cytoskeleton formation, cell proliferation and the JNK signaling pathway. GTPases generally have a low intrinsic GTPase hydrolytic activity but there are family-specific groups of GAPs that enhance the rate of GTP hydrolysis by several orders of magnitude.


Pssm-ID: 239864  Cd Length: 212  Bit Score: 45.79  E-value: 2.62e-05
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 32455248 161 LRQLLDcDTPSVDLEMI-----DVHVLADAFKRYLLDLPNPVIPAAVYSEMISLAPEVQSSEE-----YIQLLKKLIRSP 230
Cdd:cd04399  56 LRNLLN-KPKKPDKEVIilkkfEPSTVASVLKLYLLELPDSLIPHDIYDLIRSLYSAYPPSQEdsdtaRIQGLQSTLSQL 134
                        90       100
                ....*....|....*....|
gi 32455248 231 SIPHQYwlTLQYLLKHFFKL 250
Cdd:cd04399 135 PKSHIA--TLDAIITHFYRL 152
SH2_SHB cd10389
Src homology 2 domain found in SH2 domain-containing adapter protein B (SHB); SHB functions in ...
333-428 3.05e-05

Src homology 2 domain found in SH2 domain-containing adapter protein B (SHB); SHB functions in generating signaling compounds in response to tyrosine kinase activation. SHB contains proline-rich motifs, a phosphotyrosine binding (PTB) domain, tyrosine phosphorylation sites, and a SH2 domain. SHB mediates certain aspects of platelet-derived growth factor (PDGF) receptor-, fibroblast growth factor (FGF) receptor-, neural growth factor (NGF) receptor TRKA-, T cell receptor-, interleukin-2 (IL-2) receptor- and focal adhesion kinase- (FAK) signaling. SRC-like FYN-Related Kinase FRK/RAK (also named BSK/IYK or GTK) and SHB regulate apoptosis, proliferation and differentiation. SHB promotes apoptosis and is also required for proper mitogenicity, spreading and tubular morphogenesis in endothelial cells. SHB also plays a role in preventing early cavitation of embryoid bodies and reduces differentiation to cells expressing albumin, amylase, insulin and glucagon. SHB is a multifunctional protein that has difference responses in different cells under various conditions. In general SH2 domains are involved in signal transduction. They typically bind pTyr-containing ligands via two surface pockets, a pTyr and hydrophobic binding pocket, allowing proteins with SH2 domains to localize to tyrosine phosphorylated sites.


Pssm-ID: 198252  Cd Length: 97  Bit Score: 43.16  E-value: 3.05e-05
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 32455248 333 WYWGDISREEVNEKLRDTADGTFLVRDASTKMHgDYTLTLRKGGNNKLIKIFHRDGKY--GFSDPlTFSSVVELINHYRN 410
Cdd:cd10389   3 WYHGAISRGDAENLLRLCKECSYLVRNSQTSKH-DYSLSLKSNQGFMHMKLAKTKEKYvlGQNSP-PFDSVPEVIHYYTT 80
                        90
                ....*....|....*...
gi 32455248 411 ESLAQYNPKlDVKLLYPV 428
Cdd:cd10389  81 RKLPIKGAE-HLSLLYPV 97
SH2_Cterm_shark_like cd10348
C-terminal Src homology 2 (SH2) domain found in SH2 domains, ANK, and kinase domain (shark) ...
624-698 3.13e-05

C-terminal Src homology 2 (SH2) domain found in SH2 domains, ANK, and kinase domain (shark) proteins; These non-receptor protein-tyrosine kinases contain two SH2 domains, five ankyrin (ANK)-like repeats, and a potential tyrosine phosphorylation site in its carboxyl-terminal tail which resembles the phosphorylation site in members of the src family. Like, mammalian non-receptor protein-tyrosine kinases, ZAP-70 and syk proteins, they do not have SH3 domains. However, the presence of ANK makes these unique among protein-tyrosine kinases. Both tyrosine kinases and ANK repeats have been shown to transduce developmental signals, and SH2 domains are known to participate intimately in tyrosine kinase signaling. These tyrosine kinases are believed to be involved in epithelial cell polarity. The members of this family include the shark (SH2 domains, ANK, and kinase domain) gene in Drosophila and yellow fever mosquitos, as well as the hydra protein HTK16. Drosophila Shark is proposed to transduce intracellularly the Crumbs, a protein necessary for proper organization of ectodermal epithelia, intercellular signal. In general SH2 domains are involved in signal transduction. They typically bind pTyr-containing ligands via two surface pockets, a pTyr and hydrophobic binding pocket, allowing proteins with SH2 domains to localize to tyrosine phosphorylated sites.


Pssm-ID: 198211  Cd Length: 86  Bit Score: 42.79  E-value: 3.13e-05
                        10        20        30        40        50        60        70
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 32455248 624 WNVGSSNRNKAENLLRGKR--DGTFLVRESSKQ-GCYACSVVVDGEVKHCVINKTATGYGFAEPYNLYSSLKELVLHY 698
Cdd:cd10348   2 WLHGALDRNEAVEILKQKAdaDGSFLVRYSRRRpGGYVLTLVYENHVYHFEIQNRDDKWFYIDDGPYFESLEHLIEHY 79
SMC_prok_B TIGR02168
chromosome segregation protein SMC, common bacterial type; SMC (structural maintenance of ...
428-576 3.26e-05

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: 47.36  E-value: 3.26e-05
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 32455248    428 VSKYQQDQVVKEDNIEAVGKKLHEYNTQFQEKSREYDRLYEEYTRTSQEI-------QMKRTAIEAFNETIKIFEEQCQT 500
Cdd:TIGR02168  248 LKEAEEELEELTAELQELEEKLEELRLEVSELEEEIEELQKELYALANEIsrleqqkQILRERLANLERQLEELEAQLEE 327
                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 32455248    501 QERYSKEYIEKFKRegNEKEIQRIMHNYDKLKSRISE----IIDSRRR---LEEDLKKQAAEYREIDKRMNSIKPDLIQL 573
Cdd:TIGR02168  328 LESKLDELAEELAE--LEEKLEELKEELESLEAELEEleaeLEELESRleeLEEQLETLRSKVAQLELQIASLNNEIERL 405

                   ...
gi 32455248    574 RKT 576
Cdd:TIGR02168  406 EAR 408
SH2_Cterm_RasGAP cd10354
C-terminal Src homology 2 (SH2) domain found in Ras GTPase-activating protein 1 (GAP); RasGAP ...
624-698 3.32e-05

C-terminal Src homology 2 (SH2) domain found in Ras GTPase-activating protein 1 (GAP); RasGAP is part of the GAP1 family of GTPase-activating proteins. The protein is located in the cytoplasm and stimulates the GTPase activity of normal RAS p21, but not its oncogenic counterpart. Acting as a suppressor of RAS function, the protein enhances the weak intrinsic GTPase activity of RAS proteins resulting in RAS inactivation, thereby allowing control of cellular proliferation and differentiation. Mutations leading to changes in the binding sites of either protein are associated with basal cell carcinomas. Alternative splicing results in two isoforms. The shorter isoform which lacks the N-terminal hydrophobic region, has the same activity, and is expressed in placental tissues. In general longer isoform contains 2 SH2 domains, a SH3 domain, a pleckstrin homology (PH) domain, and a calcium-dependent phospholipid-binding C2 domain. The C-terminus contains the catalytic domain of RasGap which catalyzes the activation of Ras by hydrolyzing GTP-bound active Ras into an inactive GDP-bound form of Ras. This model contains the C-terminal SH2 domain. In general SH2 domains are involved in signal transduction. They typically bind pTyr-containing ligands via two surface pockets, a pTyr and hydrophobic binding pocket, allowing proteins with SH2 domains to localize to tyrosine phosphorylated sites.


Pssm-ID: 198217  Cd Length: 77  Bit Score: 42.41  E-value: 3.32e-05
                        10        20        30        40        50        60        70
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 32455248 624 WNVGSSNRNKAENLL-RGKRDGTFLVRESSKQ-GCYACSVVVDGEVKHCVINKTATG-YGFAEPYnlYSSLKELVLHY 698
Cdd:cd10354   2 WFHGKISREEAYNMLvKVGGPGSFLVRESDNTpGDYSLSFRVNEGIKHFKIIPTGNNqFMMGGRY--FSSLDDVIDRY 77
DR0291 COG1579
Predicted nucleic acid-binding protein DR0291, contains C4-type Zn-ribbon domain [General ...
448-579 3.34e-05

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: 46.07  E-value: 3.34e-05
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 32455248 448 KLHEYNTQFQEKSREYDRLYEEYTRTSQEIQMKRTAIEAFNETIKIFEEQCQTQERYSKEY---IEKFKRE----GNEKE 520
Cdd:COG1579  11 DLQELDSELDRLEHRLKELPAELAELEDELAALEARLEAAKTELEDLEKEIKRLELEIEEVearIKKYEEQlgnvRNNKE 90
                        90       100       110       120       130
                ....*....|....*....|....*....|....*....|....*....|....*....
gi 32455248 521 IQRIMHNYDKLKSRISEIIDSRRRLEEDLKKQAAEYREIDKRMNSIKPDLIQLRKTRDQ 579
Cdd:COG1579  91 YEALQKEIESLKRRISDLEDEILELMERIEELEEELAELEAELAELEAELEEKKAELDE 149
SH2_ShkA_ShkC cd10356
Src homology 2 (SH2) domain found in SH2 domain-bearing protein kinases A and C (ShkA and ShkC) ...
322-433 3.62e-05

Src homology 2 (SH2) domain found in SH2 domain-bearing protein kinases A and C (ShkA and ShkC); SH2-bearing genes cloned from Dictyostelium include two transcription factors, STATa and STATc, and a signaling factor, SHK1 (shkA). A database search of the Dictyostelium discoideum genome revealed two additional putative STAT sequences, dd-STATb and dd-STATd, and four additional putative SHK genes, dd-SHK2 (shkB), dd-SHK3 (shkC), dd-SHK4 (shkD), and dd-SHK5 (shkE). This model contains members of shkA and shkC. All of the SHK members are most closely related to the protein kinases found in plants. However these kinases in plants are not conjugated to any SH2 or SH2-like sequences. Alignment data indicates that the SHK SH2 domains carry some features of the STAT SH2 domains in Dictyostelium. When STATc's linker domain was used for a BLAST search, the sequence between the protein kinase domain and the SH2 domain (the linker) of SHK was recovered, suggesting a close relationship among these molecules within this region. SHK's linker domain is predicted to contain an alpha-helix which is indeed homologous to that of STAT. Based on the phylogenetic alignment, SH2 domains can be grouped into two categories, STAT-type and Src-type. SHK family members are in between, but are closer to the STAT-type which indicates a close relationship between SHK and STAT families in their SH2 domains and further supports the notion that SHKs linker-SH2 domain evolved from STAT or STATL (STAT-like Linker-SH2) domain found in plants. In SHK, STAT, and SPT6, the linker-SH2 domains all reside exclusively in the C-terminal regions. In general SH2 domains are involved in signal transduction. They typically bind pTyr-containing ligands via two surface pockets, a pTyr and hydrophobic binding pocket, allowing proteins with SH2 domains to localize to tyrosine phosphorylated sites.


Pssm-ID: 198219  Cd Length: 113  Bit Score: 43.36  E-value: 3.62e-05
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 32455248 322 MNNNMSLQDAEWYWGDISREEVNEKLRDTADGTFLVRDASTKmHGDYTLT-LRKGGNNKLIKIFHRDGKYGFSDPLtFSS 400
Cdd:cd10356   1 LDKIRELMECAWFHGDISTSESENRLNGKPEGTFLVRFSTSE-PGAYTISkVSKNGGISHQRIHRPGGKFQVNNSK-YLS 78
                        90       100       110
                ....*....|....*....|....*....|...
gi 32455248 401 VVELINhyRNESLAQYNPKLDVKLLYPVSKYQQ 433
Cdd:cd10356  79 VKELIA--GEAQALGIDTPCLGSRFLPLIYKMQ 109
SH2_SOCS_family cd09923
Src homology 2 (SH2) domain found in suppressor of cytokine signaling (SOCS) family; SH2 ...
624-657 4.68e-05

Src homology 2 (SH2) domain found in suppressor of cytokine signaling (SOCS) family; SH2 domain found in SOCS proteins. SOCS was first recognized as a group of cytokine-inducible SH2 (CIS) domain proteins comprising eight family members in human (CIS and SOCS1-SOCS7). In addition to the SH2 domain, SOCS proteins have a variable N-terminal domain and a conserved SOCS box in the C-terminal domain. SOCS proteins bind to a substrate via their SH2 domain. The prototypical members, CIS and SOCS1-SOCS3, have been shown to regulate growth hormone signaling in vitro and in a classic negative feedback response compete for binding at phosphotyrosine sites in JAK kinase and receptor pathways to displace effector proteins and target bound receptors for proteasomal degradation. Loss of SOCS activity results in excessive cytokine signaling associated with a variety of hematopoietic, autoimmune, and inflammatory diseases and certain cancers. Members (SOCS4-SOCS7) were identified by their conserved SOCS box, an adapter motif of 3 helices that associates substrate binding domains, such as the SOCS SH2 domain, ankryin, and WD40 with ubiquitin ligase components. These show limited cytokine induction. In general SH2 domains are involved in signal transduction. They typically bind pTyr-containing ligands via two surface pockets, a pTyr and hydrophobic binding pocket, allowing proteins with SH2 domains to localize to tyrosine phosphorylated sites.


Pssm-ID: 198178  Cd Length: 81  Bit Score: 42.19  E-value: 4.68e-05
                        10        20        30
                ....*....|....*....|....*....|....
gi 32455248 624 WNVGSSNRNKAENLLRGKRDGTFLVRESSKQGCY 657
Cdd:cd09923   2 WYWGGITRYEAEELLAGKPEGTFLVRDSSDSRYL 35
SH3_Sorbs1_3 cd11916
Third (or C-terminal) Src Homology 3 domain of Sorbin and SH3 domain containing 1 (Sorbs1), ...
6-77 4.78e-05

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: 41.52  E-value: 4.78e-05
                        10        20        30        40        50        60        70
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|..
gi 32455248   6 YQYRALYDYKKEREEDIDLHLGDILTVNKGSlvalgfsdgqearpeEIGWLNGYNETTGERGDFPGTYVEYI 77
Cdd:cd11916   2 YSYQALYSYAPQNDDELELRDGDIVDVMEKC---------------DDGWFVGTSRRTKQFGTFPGNYVKLL 58
SH2_SH2D4B cd10351
Src homology 2 domain found in the SH2 domain containing protein 4B (SH2D4B); SH2D4B contains ...
331-411 5.66e-05

Src homology 2 domain found in the SH2 domain containing protein 4B (SH2D4B); SH2D4B contains a single SH2 domain. In general SH2 domains are involved in signal transduction. They typically bind pTyr-containing ligands via two surface pockets, a pTyr and hydrophobic binding pocket, allowing proteins with SH2 domains to localize to tyrosine phosphorylated sites.


Pssm-ID: 198214  Cd Length: 103  Bit Score: 42.57  E-value: 5.66e-05
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 32455248 331 AEWYWGDISREEVNEKLRDTADGTFLVRdASTKMHGdYTLTLRKGGNNKLIKIFHRDGKYGF--SDPLTFSSVVELINHY 408
Cdd:cd10351   7 APWFHGIISREEAEALLMNATEGSFLVR-VSEKIWG-YTLSYRLQSGFKHFLVDASGDFYSFlgVDPNRHATLTDLIDFH 84

                ...
gi 32455248 409 RNE 411
Cdd:cd10351  85 KEE 87
SH2_Tec_Itk cd10396
Src homology 2 (SH2) domain found in Tec protein, IL2-inducible T-cell kinase (Itk); A member ...
328-429 5.80e-05

Src homology 2 (SH2) domain found in Tec protein, IL2-inducible T-cell kinase (Itk); A member of the Tec protein tyrosine kinase Itk is expressed thymus, spleen, lymph node, T lymphocytes, NK and mast cells. It plays a role in T-cell proliferation and differentiation, analogous to Tec family kinases Txk. Itk has been shown to interact with Fyn, Wiskott-Aldrich syndrome protein, KHDRBS1, PLCG1, Lymphocyte cytosolic protein 2, Linker of activated T cells, Karyopherin alpha 2, Grb2, and Peptidylprolyl isomerase A. Most of the Tec family members have a PH domain (Txk and the short (type 1) splice variant of Drosophila Btk29A are exceptions), a Tec homology (TH) domain, a SH3 domain, a SH2 domain, and a protein kinase catalytic domain. The TH domain consists of a Zn2+-binding Btk motif and a proline-rich region. The Btk motif is found in Tec kinases, Ras GAP, and IGBP. It is crucial for the function of Tec PH domains and it's lack of presence in Txk is not surprising since it lacks a PH domain. The type 1 splice form of the Drosophila homolog also lacks both the PH domain and the Btk motif. The proline-rich regions are highly conserved for the most part with the exception of Bmx whose residues surrounding the PXXP motif are not conserved (TH-like) and Btk29A which is entirely unique with large numbers of glycine residues (TH-extended). Tec family members all lack a C-terminal tyrosine having an autoinhibitory function in its phosphorylated state. In general SH2 domains are involved in signal transduction. They typically bind pTyr-containing ligands via two surface pockets, a pTyr and hydrophobic binding pocket, allowing proteins with SH2 domains to localize to tyrosine phosphorylated sites.


Pssm-ID: 198259  Cd Length: 108  Bit Score: 42.86  E-value: 5.80e-05
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 32455248 328 LQDAEWYWGDISREEVNEKLRDTA-DGTFLVRDASTKmhGDYTLTLRK---GGNNKLIKIFH------RDGKYGFSDPLT 397
Cdd:cd10396   3 LDQYEWYNKNINRSKAEKLLRDEGkEGGFMVRDSSQP--GLYTVSLYTkagGEGNPCIRHYHiketndSPKKYYLAEKHV 80
                        90       100       110
                ....*....|....*....|....*....|...
gi 32455248 398 FSSVVELINHYrneslaQYNPK-LDVKLLYPVS 429
Cdd:cd10396  81 FNSIPELIEYH------KHNAAgLVTRLRYPVS 107
SH2_SHB_SHD_SHE_SHF_like cd09945
Src homology 2 domain found in SH2 domain-containing adapter proteins B, D, E, and F (SHB, SHD, ...
624-718 5.90e-05

Src homology 2 domain found in SH2 domain-containing adapter proteins B, D, E, and F (SHB, SHD, SHE, SHF); SHB, SHD, SHE, and SHF are SH2 domain-containing proteins that play various roles throughout the cell. SHB functions in generating signaling compounds in response to tyrosine kinase activation. SHB contains proline-rich motifs, a phosphotyrosine binding (PTB) domain, tyrosine phosphorylation sites, and a SH2 domain. SHB mediates certain aspects of platelet-derived growth factor (PDGF) receptor-, fibroblast growth factor (FGF) receptor-, neural growth factor (NGF) receptor TRKA-, T cell receptor-, interleukin-2 (IL-2) receptor- and focal adhesion kinase- (FAK) signaling. SRC-like FYN-Related Kinase FRK/RAK (also named BSK/IYK or GTK) and SHB regulate apoptosis, proliferation and differentiation. SHB promotes apoptosis and is also required for proper mitogenicity, spreading and tubular morphogenesis in endothelial cells. SHB also plays a role in preventing early cavitation of embryoid bodies and reduces differentiation to cells expressing albumin, amylase, insulin and glucagon. SHB is a multifunctional protein that has difference responses in different cells under various conditions. SHE is expressed in heart, lung, brain, and skeletal muscle, while expression of SHD is restricted to the brain. SHF is mainly expressed in skeletal muscle, brain, liver, prostate, testis, ovary, small intestine, and colon. SHD may be a physiological substrate of c-Abl and may function as an adapter protein in the central nervous system. It is also thought to be involved in apoptotic regulation. SHD contains five YXXP motifs, a substrate sequence preferred by Abl tyrosine kinases, in addition to a poly-proline rich region and a C-terminal SH2 domain. SHE contains two pTry protein binding domains, protein interaction domain (PID) and a SH2 domain, followed by a glycine-proline rich region, all of which are N-terminal to the phosphotyrosine binding (PTB) domain. SHF contains four putative tyrosine phosphorylation sites and an SH2 domain. In general SH2 domains are involved in signal transduction. They typically bind pTyr-containing ligands via two surface pockets, a pTyr and hydrophobic binding pocket, allowing proteins with SH2 domains to localize to tyrosine phosphorylated sites.


Pssm-ID: 198198  Cd Length: 98  Bit Score: 42.41  E-value: 5.90e-05
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 32455248 624 WNVGSSNRNKAENLLRGKRDGTFLVR--ESSKQGcYACSVVVDGEVKHCVINKTATG-YGFAEPYNLYSSLKELVLHYQH 700
Cdd:cd09945   3 WYHGAITRIEAESLLRPCKEGSYLVRnsESTKQD-YSLSLKSAKGFMHMRIQRNETGqYILGQFSRPFETIPEMIRHYCL 81
                        90       100
                ....*....|....*....|..
gi 32455248 701 TSL----VQHndslnVTLAYPV 718
Cdd:cd09945  82 NKLpvrgAEH-----MCLLEPV 98
RhoGAP_DLC1 cd04375
RhoGAP_DLC1: RhoGAP (GTPase-activator protein [GAP] for Rho-like small GTPases) domain of ...
156-283 5.96e-05

RhoGAP_DLC1: RhoGAP (GTPase-activator protein [GAP] for Rho-like small GTPases) domain of DLC1-like proteins. DLC1 shows in vitro GAP activity towards RhoA and CDC42. Beside its C-terminal GAP domain, DLC1 also contains a SAM (sterile alpha motif) and a START (StAR-related lipid transfer action) domain. DLC1 has tumor suppressor activity in cell culture. Small GTPases cluster into distinct families, and all act as molecular switches, active in their GTP-bound form but inactive when GDP-bound. The Rho family of GTPases activates effectors involved in a wide variety of developmental processes, including regulation of cytoskeleton formation, cell proliferation and the JNK signaling pathway. GTPases generally have a low intrinsic GTPase hydrolytic activity but there are family-specific groups of GAPs that enhance the rate of GTP hydrolysis by several orders of magnitude.


Pssm-ID: 239840  Cd Length: 220  Bit Score: 45.10  E-value: 5.96e-05
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 32455248 156 SNLAELRQLLDCDTPSVDLEMIDVHVLADAFKRYLLDLPNPVIPAAVySEMISLAPEVQSSEEYIQLLKKLIRspSIPHQ 235
Cdd:cd04375  49 SRIQKLRSMIESSTDNVNYDGQQAYDVADMLKQYFRDLPEPLLTNKL-SETFIAIFQYVPKEQRLEAVQCAIL--LLPDE 125
                        90       100       110       120
                ....*....|....*....|....*....|....*....|....*...
gi 32455248 236 YWLTLQYLLKHFFKLSQTSSKNLLNARVLSEIFSPMLFRFSAASSDNT 283
Cdd:cd04375 126 NREVLQTLLYFLSDVAANSQENQMTATNLAVCLAPSLFHLNTSRRENS 173
SH3_MYO7A cd11881
Src Homology 3 domain of Myosin VIIa and similar proteins; Myo7A is an uncoventional myosin ...
10-74 6.12e-05

Src Homology 3 domain of Myosin VIIa and similar proteins; Myo7A is an uncoventional myosin that is involved in organelle transport. It is required for sensory function in both Drosophila and mammals. Mutations in the Myo7A gene cause both syndromic deaf-blindness [Usher syndrome I (USH1)] and nonsyndromic (DFNB2 and DFNA11) deafness in humans. It contains an N-terminal motor domain, light chain-binding IQ motifs, a coiled-coil region for heavy chain dimerization, and a tail consisting of a pair of MyTH4-FERM tandems separated by a 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: 212814  Cd Length: 64  Bit Score: 41.34  E-value: 6.12e-05
                        10        20        30        40        50        60
                ....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 32455248  10 ALYDYKKEREEDidlhlgDILTVNKGSLVALGFSDGQEARPEeiGWLNGYNETTGERGDFPGTYV 74
Cdd:cd11881   6 ALQDYPNPSDGS------SFLSFAKGDLIILDQDTGEQVMNS--GWCNGRNDRTGQRGDFPADCV 62
SH2_Src_Lck cd10362
Src homology 2 (SH2) domain in lymphocyte cell kinase (Lck); Lck is a member of the Src ...
329-412 6.67e-05

Src homology 2 (SH2) domain in lymphocyte cell kinase (Lck); Lck is a member of the Src non-receptor type tyrosine kinase family of proteins. It is expressed in the brain, T-cells, and NK cells. The unique domain of Lck mediates its interaction with two T-cell surface molecules, CD4 and CD8. It associates with their cytoplasmic tails on CD4 T helper cells and CD8 cytotoxic T cells to assist signaling from the T cell receptor (TCR) complex. When the T cell receptor is engaged by the specific antigen presented by MHC, Lck phosphorylase the intracellular chains of the CD3 and zeta-chains of the TCR complex, allowing ZAP-70 to bind them. Lck then phosphorylates and activates ZAP-70, which in turn phosphorylates Linker of Activated T cells (LAT), a transmembrane protein that serves as a docking site for proteins including: Shc-Grb2-SOS, PI3K, and phospholipase C (PLC). The tyrosine phosphorylation cascade culminates in the intracellular mobilization of a calcium ions and activation of important signaling cascades within the lymphocyte, including the Ras-MEK-ERK pathway, which goes on to activate certain transcription factors such as NFAT, NF-kappaB, and AP-1. These transcription factors regulate the production cytokines such as Interleukin-2 that promote long-term proliferation and differentiation of the activated lymphocytes. The N-terminal tail of Lck is myristoylated and palmitoylated and it tethers the protein to the plasma membrane of the cell. Lck also contains a SH3 domain, a SH2 domain, and a C-terminal tyrosine kinase domain. Lck has 2 phosphorylation sites, the first an autophosphorylation site that is linked to activation of the protein and the second which is phosphorylated by Csk, which inhibits it. Lck is also inhibited by SHP-1 dephosphorylation and by Cbl ubiquitin ligase, which is part of the ubiquitin-mediated pathway. In general SH2 domains are involved in signal transduction. They typically bind pTyr-containing ligands via two surface pockets, a pTyr and hydrophobic binding pocket, allowing proteins with SH2 domains to localize to tyrosine phosphorylated sites.


Pssm-ID: 198225  Cd Length: 101  Bit Score: 42.55  E-value: 6.67e-05
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 32455248 329 QDAEWYWGDISREEVNEKLRDTAD--GTFLVRDASTKmHGDYTLTLR-----KGGNNKLIKIFHRD-GKYGFSDPLTFSS 400
Cdd:cd10362   1 EPEPWFFKNLSRNDAERQLLAPGNthGSFLIRESETT-AGSFSLSVRdfdqnQGEVVKHYKIRNLDnGGFYISPRITFPG 79
                        90
                ....*....|..
gi 32455248 401 VVELINHYRNES 412
Cdd:cd10362  80 LHELVRHYTNAS 91
AAA_13 pfam13166
AAA domain; This family of domains contain a P-loop motif that is characteriztic of the AAA ...
411-568 9.08e-05

AAA domain; This family of domains contain a P-loop motif that is characteriztic of the AAA superfamily. Many of the proteins in this family are conjugative transfer proteins. This family includes the PrrC protein that is thought to be the active component of the anticodon nuclease.


Pssm-ID: 463796 [Multi-domain]  Cd Length: 712  Bit Score: 45.82  E-value: 9.08e-05
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 32455248   411 ESLAQYNPKLDVKLLYPVSKYQQDQVvkEDNIEAVGKKLHEYNTQFQEK------SREYDRLYEEYTRTSQEIQMKRTAI 484
Cdd:pfam13166 301 SLLAQLPAVSDLASLLSAFELDVEDI--ESEAEVLNSQLDGLRRALEAKrkdpfkSIELDSVDAKIESINDLVASINELI 378
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 32455248   485 EAFNETIKIFEEQCQTqerySKEYIEKFKREGNEKEIQRIMHNYDKLKSRISEIIDSRRRLEEDLKKQAAEYREIDKRMN 564
Cdd:pfam13166 379 AKHNEITDNFEEEKNK----AKKKLRLHLVEEFKSEIDEYKDKYAGLEKAINSLEKEIKNLEAEIKKLREEIKELEAQLR 454

                  ....
gi 32455248   565 SIKP 568
Cdd:pfam13166 455 DHKP 458
SH3_SNX18 cd11897
Src Homology 3 domain of Sorting nexin 18; SNX18 is localized to peripheral endosomal ...
9-75 9.88e-05

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: 40.74  E-value: 9.88e-05
                        10        20        30        40        50        60
                ....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 32455248   9 RALYDYKKEREEDIDLHLGDILTVnkgslvalgfsdgqeARPEEI-GWLNGYNeTTGERGDFPGTYVE 75
Cdd:cd11897   3 RALYDFRSENPGEISLREHEVLSL---------------CSEQDIeGWLEGVN-SRGDRGLFPASYVE 54
DR0291 COG1579
Predicted nucleic acid-binding protein DR0291, contains C4-type Zn-ribbon domain [General ...
447-580 1.15e-04

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: 44.15  E-value: 1.15e-04
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 32455248 447 KKLHEYNTQFQEKSREYDRLYEEYTRTSQEIQMKRTAIEAFNETIKIFEEQcQTQERYSKEY------IEKFKRE--GNE 518
Cdd:COG1579  31 AELAELEDELAALEARLEAAKTELEDLEKEIKRLELEIEEVEARIKKYEEQ-LGNVRNNKEYealqkeIESLKRRisDLE 109
                        90       100       110       120       130       140
                ....*....|....*....|....*....|....*....|....*....|....*....|..
gi 32455248 519 KEIQRIMHNYDKLKSRISEIIDSRRRLEEDLKKQAAeyrEIDKRMNSIKPDLIQLRKTRDQY 580
Cdd:COG1579 110 DEILELMERIEELEEELAELEAELAELEAELEEKKA---ELDEELAELEAELEELEAEREEL 168
SH2_SH2D4A cd10350
Src homology 2 domain found in the SH2 domain containing protein 4A (SH2D4A); SH2D4A contains ...
624-699 1.44e-04

Src homology 2 domain found in the SH2 domain containing protein 4A (SH2D4A); SH2D4A contains a single SH2 domain. In general SH2 domains are involved in signal transduction. They typically bind pTyr-containing ligands via two surface pockets, a pTyr and hydrophobic binding pocket, allowing proteins with SH2 domains to localize to tyrosine phosphorylated sites.


Pssm-ID: 198213  Cd Length: 103  Bit Score: 41.45  E-value: 1.44e-04
                        10        20        30        40        50        60        70
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 32455248 624 WNVGSSNRNKAENLLRGKRDGTFLVRESSKQGCYACSVVVDGEVKHCVINKTATGYGFAEPYNL-YSSLKELVLHYQ 699
Cdd:cd10350   9 WFHGILTLKKANELLLSTMPGSFLIRVSEKIKGYALSYLSEEGCKHFLIDASADSYSFLGVDQLqHATLADLVEYHK 85
SH2_Tensin_like cd09927
Src homology 2 domain found in Tensin-like proteins; SH2 domain found in Tensin-like proteins. ...
333-373 1.48e-04

Src homology 2 domain found in Tensin-like proteins; SH2 domain found in Tensin-like proteins. The Tensins are a family of intracellular proteins that interact with receptor tyrosine kinases (RTKs), integrins, and actin. They are thought act as signaling bridges between the extracellular space and the cytoskeleton. There are four homologues: Tensin1, Tensin2 (TENC1, C1-TEN), Tensin3 and Tensin4 (cten), all of which contain a C-terminal tandem SH2-PTB domain pairing, as well as actin-binding regions that may localize them to focal adhesions. The isoforms of Tensin2 and Tensin3 contain N-terminal C1 domains, which are atypical and not expected to bind to phorbol esters. Tensins 1-3 contain a phosphatase (PTPase) and C2 domain pairing which resembles PTEN (phosphatase and tensin homologue deleted on chromosome 10) protein. PTEN is a lipid phosphatase that dephosphorylates phosphatidylinositol 3,4,5-trisphosphate (PtdIns(3,4,5)P3) to yield phosphatidylinositol 4,5-bisphosphate (PtdIns(4,5)P2). As PtdIns(3,4,5)P3 is the product of phosphatidylinositol 3-kinase (PI3K) activity, PTEN is therefore a key negative regulator of the PI3K pathway. Because of their PTEN-like domains, the Tensins may also possess phosphoinositide-binding or phosphatase capabilities. However, only Tensin2 and Tensin3 have the potential to be phosphatases since only their PTPase domains contain a cysteine residue that is essential for catalytic activity. In general SH2 domains are involved in signal transduction. They typically bind pTyr-containing ligands via two surface pockets, a pTyr and hydrophobic binding pocket, allowing proteins with SH2 domains to localize to tyrosine phosphorylated sites.


Pssm-ID: 198181 [Multi-domain]  Cd Length: 116  Bit Score: 42.03  E-value: 1.48e-04
                        10        20        30        40
                ....*....|....*....|....*....|....*....|.
gi 32455248 333 WYWGDISREEVNEKLRDTADGTFLVRDaSTKMHGDYTLTLR 373
Cdd:cd09927   5 WYKPNISRDQAIALLKDKPPGTFLVRD-STTYKGAYGLAVK 44
RhoGAP_KIAA1688 cd04389
RhoGAP_KIAA1688: GTPase-activator protein (GAP) domain for Rho-like GTPases found in ...
156-294 1.50e-04

RhoGAP_KIAA1688: GTPase-activator protein (GAP) domain for Rho-like GTPases found in KIAA1688-like proteins; KIAA1688 is a protein of unknown function that contains a RhoGAP domain and a myosin tail homology 4 (MyTH4) domain. Small GTPases cluster into distinct families, and all act as molecular switches, active in their GTP-bound form but inactive when GDP-bound. The Rho family of GTPases activates effectors involved in a wide variety of developmental processes, including regulation of cytoskeleton formation, cell proliferation and the JNK signaling pathway. GTPases generally have a low intrinsic GTPase hydrolytic activity but there are family-specific groups of GAPs that enhance the rate of GTP hydrolysis by several orders of magnitude.


Pssm-ID: 239854  Cd Length: 187  Bit Score: 43.15  E-value: 1.50e-04
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 32455248 156 SNLAELRQLLD-CDTPSVDLEmiDVHVLADAFKRYLLDLPNPVIPAAVYSEMISLAPEVQSSEEYIQLLKKLIRspsiph 234
Cdd:cd04389  51 DEVNELKLRVDqWDYPLSGLE--DPHVPASLLKLWLRELEEPLIPDALYQQCISASEDPDKAVEIVQKLPIINR------ 122
                        90       100       110       120       130       140
                ....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 32455248 235 qywLTLQYLLkHF---FKLSQTSSKNLLNARVLSEIFSPMLFRFSAASS----DNTENLIKVIEILI 294
Cdd:cd04389 123 ---LVLCYLI-NFlqvFAQPENVAHTKMDVSNLAMVFAPNILRCTSDDPrvifENTRKEMSFLRTLI 185
SH2_Srm cd10360
Src homology 2 (SH2) domain found in Src-related kinase lacking C-terminal regulatory tyrosine ...
624-698 1.80e-04

Src homology 2 (SH2) domain found in Src-related kinase lacking C-terminal regulatory tyrosine and N-terminal myristoylation sites (srm); Srm is a nonreceptor protein kinase that has two SH2 domains, a SH3 domain, and a kinase domain with a tyrosine residue for autophosphorylation. However it lacks an N-terminal glycine for myristoylation and a C-terminal tyrosine which suppresses kinase activity when phosphorylated. Srm is most similar to members of the Tec family who other members include: Tec, Btk/Emb, and Itk/Tsk/Emt. However Srm differs in its N-terminal unique domain it being much smaller than in the Tec family and is closer to Src. Srm is thought to be a new family of nonreceptor tyrosine kinases that may be redundant in function. In general SH2 domains are involved in signal transduction. They typically bind pTyr-containing ligands via two surface pockets, a pTyr and hydrophobic binding pocket, allowing proteins with SH2 domains to localize to tyrosine phosphorylated sites.


Pssm-ID: 198223  Cd Length: 79  Bit Score: 40.71  E-value: 1.80e-04
                        10        20        30        40        50        60        70
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 32455248 624 WNVGSSNRNKAENLLRG--KRDGTFLVRES-SKQGCYACSVVVDGEVKHCVINKTATGYGFAEPYNLYSSLKELVLHY 698
Cdd:cd10360   2 WYFSGISRTQAQQLLLSppNEPGAFLIRPSeSSLGGYSLSVRAQAKVCHYRICMAPSGSLYLQKGRLFPGLEELLAYY 79
SH2_N-SH2_SHP_like cd10340
N-terminal Src homology 2 (N-SH2) domain found in SH2 domain Phosphatases (SHP) proteins; The ...
333-428 1.82e-04

N-terminal Src homology 2 (N-SH2) domain found in SH2 domain Phosphatases (SHP) proteins; The SH2 domain phosphatases (SHP-1, SHP-2/Syp, Drosophila corkscrew (csw), and Caenorhabditis elegans Protein Tyrosine Phosphatase (Ptp-2)) are cytoplasmic signaling enzymes. They are both targeted and regulated by interactions of their SH2 domains with phosphotyrosine docking sites. These proteins contain two SH2 domains (N-SH2, C-SH2) followed by a tyrosine phosphatase (PTP) domain, and a C-terminal extension. Shp1 and Shp2 have two tyrosyl phosphorylation sites in their C-tails, which are phosphorylated differentially by receptor and nonreceptor PTKs. Csw retains the proximal tyrosine and Ptp-2 lacks both sites. Shp-binding proteins include receptors, scaffolding adapters, and inhibitory receptors. Some of these bind both Shp1 and Shp2 while others bind only one. Most proteins that bind a Shp SH2 domain contain one or more immuno-receptor tyrosine-based inhibitory motifs (ITIMs): [IVL]xpYxx[IVL]. Shp1 N-SH2 domain blocks the catalytic domain and keeps the enzyme in the inactive conformation, and is thus believed to regulate the phosphatase activity of SHP-1. Its C-SH2 domain is thought to be involved in searching for phosphotyrosine activators. The SHP2 N-SH2 domain is a conformational switch; it either binds and inhibits the phosphatase, or it binds phosphoproteins and activates the enzyme. The C-SH2 domain contributes binding energy and specificity, but it does not have a direct role in activation. Csw SH2 domain function is essential, but either SH2 domain can fulfill this requirement. The role of the csw SH2 domains during Sevenless receptor tyrosine kinase (SEV) signaling is to bind Daughter of Sevenless rather than activated SEV. Ptp-2 acts in oocytes downstream of sheath/oocyte gap junctions to promote major sperm protein (MSP)-induced MAP Kinase (MPK-1) phosphorylation. Ptp-2 functions in the oocyte cytoplasm, not at the cell surface to inhibit multiple RasGAPs, resulting in sustained Ras activation. It is thought that MSP triggers PTP-2/Ras activation and ROS production to stimulate MPK-1 activity essential for oocyte maturation and that secreted MSP domains and Cu/Zn superoxide dismutases function antagonistically to control ROS and MAPK signaling. In general SH2 domains are involved in signal transduction. They typically bind pTyr-containing ligands via two surface pockets, a pTyr and hydrophobic binding pocket, allowing proteins with SH2 domains to localize to tyrosine phosphorylated sites.


Pssm-ID: 198203  Cd Length: 99  Bit Score: 41.23  E-value: 1.82e-04
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 32455248 333 WYWGDISREEVNEKLRDTA-DGTFLVRdASTKMHGDYTLTLRKGGNNKLIKIFHRDGKYGFSDPLTFSSVVELINHY-RN 410
Cdd:cd10340   2 WFHPVISGIEAENLLKTRGvDGSFLAR-PSKSNPGDFTLSVRRGDEVTHIKIQNTGDYYDLYGGEKFATLSELVQYYmEQ 80
                        90
                ....*....|....*...
gi 32455248 411 ESLAQYNPKLDVKLLYPV 428
Cdd:cd10340  81 HGQLREKNGDVIELKYPL 98
SH2_SHIP cd10343
Src homology 2 (SH2) domain found in SH2-containing inositol-5'-phosphatase (SHIP) and ...
329-430 2.15e-04

Src homology 2 (SH2) domain found in SH2-containing inositol-5'-phosphatase (SHIP) and SLAM-associated protein (SAP); The SH2-containing inositol-5'-phosphatase, SHIP (also called SHIP1/SHIP1a), is a hematopoietic-restricted phosphatidylinositide phosphatase that translocates to the plasma membrane after extracellular stimulation and hydrolyzes the phosphatidylinositol-3-kinase (PI3K)-generated second messenger PI-3,4,5-P3 (PIP3) to PI-3,4-P2. As a result, SHIP dampens down PIP3 mediated signaling and represses the proliferation, differentiation, survival, activation, and migration of hematopoietic cells. PIP3 recruits lipid-binding pleckstrin homology(PH) domain-containing proteins to the inner wall of the plasma membrane and activates them. PH domain-containing downstream effectors include the survival/proliferation enhancing serine/threonine kinase, Akt (protein kinase B), the tyrosine kinase, Btk, the regulator of protein translation, S6K, and the Rac and cdc42 guanine nucleotide exchange factor, Vav. SHIP is believed to act as a tumor suppressor during leukemogenesis and lymphomagenesis, and may play a role in activating the immune system to combat cancer. SHIP contains an N-terminal SH2 domain, a centrally located phosphatase domain that specifically hydrolyzes the 5'-phosphate from PIP3, PI-4,5-P2 and inositol-1,3,4,5- tetrakisphosphate (IP4), a C2 domain, that is an allosteric activating site when bound by SHIP's enzymatic product, PI-3,4-P2; 2 NPXY motifs that bind proteins with a phosphotyrosine binding (Shc, Dok 1, Dok 2) or an SH2 (p85a, SHIP2) domain; and a proline-rich domain consisting of four PxxP motifs that bind a subset of SH3-containing proteins including Grb2, Src, Lyn, Hck, Abl, PLCg1, and PIAS1. The SH2 domain of SHIP binds to the tyrosine phosphorylated forms of Shc, SHP-2, Doks, Gabs, CD150, platelet-endothelial cell adhesion molecule, Cas, c-Cbl, immunoreceptor tyrosine-based inhibitory motifs (ITIMs), and immunoreceptor tyrosine-based activation motifs (ITAMs). The X-linked lymphoproliferative syndrome (XLP) gene encodes SAP (also called SH2D1A/DSHP) a protein that consists of a 5 residue N-terminus, a single SH2 domain, and a short 25 residue C-terminal tail. XLP is characterized by an extreme sensitivity to Epstein-Barr virus. Both T and natural killer (NK) cell dysfunctions have been seen in XLP patients. SAP binds the cytoplasmic tail of Signaling lymphocytic activation molecule (SLAM), 2B4, Ly-9, and CD84. SAP is believed to function as a signaling inhibitor, by blocking or regulating binding of other signaling proteins. SAP and the SAP-like protein EAT-2 recognize the sequence motif TIpYXX(V/I), which is found in the cytoplasmic domains of a restricted number of T, B, and NK cell surface receptors and are proposed to be natural inhibitors or regulators of the physiological role of a small family of receptors on the surface of these cells. In general SH2 domains are involved in signal transduction. They typically bind pTyr-containing ligands via two surface pockets, a pTyr and hydrophobic binding pocket, allowing proteins with SH2 domains to localize to tyrosine phosphorylated sites.


Pssm-ID: 198206  Cd Length: 103  Bit Score: 40.89  E-value: 2.15e-04
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 32455248 329 QDAEWYWGDISREEVNEKL-RDTADGTFLVRDaSTKMHGDYTLTLRKGGNNKLIKIF-HRDGKYGFS-----DPLTFSSV 401
Cdd:cd10343   1 MAPPWYHGNITRSKAEELLsKAGKDGSFLVRD-SESVSGAYALCVLYQNCVHTYRILpNAEDKLSVQasegvPVRFFTTL 79
                        90       100
                ....*....|....*....|....*....
gi 32455248 402 VELINHYRNEslaqyNPKLDVKLLYPVSK 430
Cdd:cd10343  80 PELIEFYQKE-----NMGLVTHLLYPVER 103
SH2_SH2D2A_SH2D7 cd10349
Src homology 2 domain found in the SH2 domain containing protein 2A and 7 (SH2D2A and SH2D7); ...
624-698 2.43e-04

Src homology 2 domain found in the SH2 domain containing protein 2A and 7 (SH2D2A and SH2D7); SH2D2A and SH7 both contain a single SH2 domain. In general SH2 domains are involved in signal transduction. They typically bind pTyr-containing ligands via two surface pockets, a pTyr and hydrophobic binding pocket, allowing proteins with SH2 domains to localize to tyrosine phosphorylated sites.


Pssm-ID: 199830  Cd Length: 77  Bit Score: 40.20  E-value: 2.43e-04
                        10        20        30        40        50        60        70
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 32455248 624 WNVGSSNRNKAENLLRGKRDGTFLVRESSKQGCYACSVVVDGEVKHCVINKTATG-YGFAEPYNLYSSLKELVLHY 698
Cdd:cd10349   2 WFHGFITRREAERLLEPKPQGCYLVRFSESAVTFVLSYRSRTCCRHFLLAQLRDGrHVVLGEDSAHARLQDLLLHY 77
SH2_C-SH2_Zap70 cd10402
C-terminal Src homology 2 (SH2) domain found in Zeta-chain-associated protein kinase 70 ...
619-678 2.64e-04

C-terminal Src homology 2 (SH2) domain found in Zeta-chain-associated protein kinase 70 (ZAP-70); ZAP-70 and Syk comprise a family of hematopoietic cell specific protein tyrosine kinases (PTKs) that are required for antigen and antibody receptor function. ZAP-70 is expressed in T and natural killer (NK) cells and Syk is expressed in B cells, mast cells, polymorphonuclear leukocytes, platelets, macrophages, and immature T cells. They are required for the proper development of T and B cells, immune receptors, and activating NK cells. They consist of two N-terminal Src homology 2 (SH2) domains and a C-terminal kinase domain separated from the SH2 domains by a linker or hinge region. Phosphorylation of both tyrosine residues within the Immunoreceptor Tyrosine-based Activation Motifs (ITAM; consensus sequence Yxx[LI]x(7,8)Yxx[LI]) by the Src-family PTKs is required for efficient interaction of ZAP-70 and Syk with the receptor subunits and for receptor function. ZAP-70 forms two phosphotyrosine binding pockets, one of which is shared by both SH2 domains. In Syk the two SH2 domains do not form such a phosphotyrosine-binding site. The SH2 domains here are believed to function independently. In addition, the two SH2 domains of Syk display flexibility in their relative orientation, allowing Syk to accommodate a greater variety of spacing sequences between the ITAM phosphotyrosines and singly phosphorylated non-classical ITAM ligands. This model contains the C-terminus SH2 domains of Zap70. In general SH2 domains are involved in signal transduction. They typically bind pTyr-containing ligands via two surface pockets, a pTyr and hydrophobic binding pocket, allowing proteins with SH2 domains to localize to tyrosine phosphorylated sites.


Pssm-ID: 198265  Cd Length: 105  Bit Score: 40.67  E-value: 2.64e-04
                        10        20        30        40        50        60
                ....*....|....*....|....*....|....*....|....*....|....*....|..
gi 32455248 619 HDEKTWNVGSSNRNKAENLLR--GKRDGTFLVRESSKQGCYACSVVVDGEVKHCVINKTATG 678
Cdd:cd10402   7 HERMPWYHGSIARDEAERRLYsgAQPDGKFLLRERKESGTYALSLVYGKTVYHYRIDQDKSG 68
SH3_Bzz1_2 cd11778
Second Src Homology 3 domain of Bzz1 and similar domains; Bzz1 (or Bzz1p) is a WASP ...
10-73 2.89e-04

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: 39.02  E-value: 2.89e-04
                        10        20        30        40        50        60
                ....*....|....*....|....*....|....*....|....*....|....*....|....
gi 32455248  10 ALYDYKKEREEDIDLHLGDILTVNKGslvalgfSDGQearpeeiGWLngYNETTGERGDFPGTY 73
Cdd:cd11778   4 ALYDYEAQGDDEISIRVGDRIAVIRG-------DDGS-------GWT--YGEINGVKGLFPTSY 51
SH2_Tec_Bmx cd10399
Src homology 2 (SH2) domain found in Tec protein, Bmx; A member of the Tec protein tyrosine ...
327-412 3.33e-04

Src homology 2 (SH2) domain found in Tec protein, Bmx; A member of the Tec protein tyrosine kinase Bmx is expressed in the endothelium of large arteries, fetal endocardium, adult endocardium of the left ventricle, bone marrow, lung, testis, granulocytes, myeloid cell lines, and prostate cell lines. Bmx is involved in the regulation of Rho and serum response factor (SRF). Bmx has been shown to interact with PAK1, PTK2, PTPN21, and RUFY1. Most of the Tec family members have a PH domain (Txk and the short (type 1) splice variant of Drosophila Btk29A are exceptions), a Tec homology (TH) domain, a SH3 domain, a SH2 domain, and a protein kinase catalytic domain. The TH domain consists of a Zn2+-binding Btk motif and a proline-rich region. The Btk motif is found in Tec kinases, Ras GAP, and IGBP. It is crucial for the function of Tec PH domains. It is not present in Txk and the type 1 splice form of the Drosophila homolog. The proline-rich regions are highly conserved for the most part with the exception of Bmx whose residues surrounding the PXXP motif are not conserved (TH-like) and Btk29A which is entirely unique with large numbers of glycine residues (TH-extended). Tec family members all lack a C-terminal tyrosine having an autoinhibitory function in its phosphorylated state. In general SH2 domains are involved in signal transduction. They typically bind pTyr-containing ligands via two surface pockets, a pTyr and hydrophobic binding pocket, allowing proteins with SH2 domains to localize to tyrosine phosphorylated sites.


Pssm-ID: 198262  Cd Length: 106  Bit Score: 40.71  E-value: 3.33e-04
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 32455248 327 SLQDAEWYWGDISREEVNEKLRDTA-DGTFLVRDASTKmhGDYTLT-LRKGGNNK--LIKIFH----RDGKYGFSDPLTF 398
Cdd:cd10399   2 NLDAYDWFAGNISRSQSEQLLRQKGkEGAFMVRNSSQV--GMYTVSlFSKAVNDKkgTVKHYHvhtnAENKLYLAENYCF 79
                        90
                ....*....|....
gi 32455248 399 SSVVELINHYRNES 412
Cdd:cd10399  80 DSIPKLIHYHQHNS 93
SH3_Endophilin_A cd11803
Src homology 3 domain of Endophilin-A; Endophilins play roles in synaptic vesicle formation, ...
7-77 3.48e-04

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: 39.17  E-value: 3.48e-04
                        10        20        30        40        50        60        70
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|.
gi 32455248   7 QYRALYDYKKEREEDIDLHLGDILTVnkgslvalgfsdgqEARPEEiGWLNGynETTGERGDFPGTYVEYI 77
Cdd:cd11803   2 CCRALYDFEPENEGELGFKEGDIITL--------------TNQIDE-NWYEG--MVNGQSGFFPVNYVEVL 55
SH3_Intersectin_1 cd11836
First Src homology 3 domain (or SH3A) of Intersectin; Intersectins (ITSNs) are adaptor ...
8-75 3.73e-04

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: 38.88  E-value: 3.73e-04
                        10        20        30        40        50        60
                ....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 32455248   8 YRALYDYKKEREEDIDLHLGDILTVNkgslvalgfsDGQEARPeeiGWLNGynETTGERGDFPGTYVE 75
Cdd:cd11836   2 YRALYAFEARNPDEISFQPGDIIQVD----------ESQVAEP---GWLAG--ELKGKTGWFPANYVE 54
SH2_Src_Fgr cd10367
Src homology 2 (SH2) domain found in Gardner-Rasheed feline sarcoma viral (v-fgr) oncogene ...
622-717 4.43e-04

Src homology 2 (SH2) domain found in Gardner-Rasheed feline sarcoma viral (v-fgr) oncogene homolog, Fgr; Fgr is a member of the Src non-receptor type tyrosine kinase family of proteins. The protein contains N-terminal sites for myristoylation and palmitoylation, a PTK domain, and SH2 and SH3 domains which are involved in mediating protein-protein interactions with phosphotyrosine-containing and proline-rich motifs, respectively. Fgr is expressed in B-cells and myeloid cells, localizes to plasma membrane ruffles, and functions as a negative regulator of cell migration and adhesion triggered by the beta-2 integrin signal transduction pathway. Multiple alternatively spliced variants, encoding the same protein, have been identified Fgr has been shown to interact with Wiskott-Aldrich syndrome protein. Fgr has a unique N-terminal domain, an SH3 domain, an SH2 domain, a kinase domain and a regulatory tail, as do the other members of the family. In general SH2 domains are involved in signal transduction. They typically bind pTyr-containing ligands via two surface pockets, a pTyr and hydrophobic binding pocket, allowing proteins with SH2 domains to localize to tyrosine phosphorylated sites.


Pssm-ID: 198230  Cd Length: 101  Bit Score: 40.27  E-value: 4.43e-04
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 32455248 622 KTWNVGSSNRNKAENLL--RGKRDGTFLVRES-SKQGCYACSV-----VVDGEVKHCVINKTATGYGFAEPYNLYSSLKE 693
Cdd:cd10367   3 EEWYFGKIGRKDAERQLlsPGNPRGAFLIRESeTTKGAYSLSIrdwdqNRGDHVKHYKIRKLDTGGYYITTRAQFDTVQE 82
                        90       100
                ....*....|....*....|....
gi 32455248 694 LVLHYqhtslVQHNDSLNVTLAYP 717
Cdd:cd10367  83 LVQHY-----MEVNDGLCYLLTAP 101
SH2_Grb7_family cd09944
Src homology 2 (SH2) domain found in the growth factor receptor bound, subclass 7 (Grb7) ...
619-672 4.44e-04

Src homology 2 (SH2) domain found in the growth factor receptor bound, subclass 7 (Grb7) proteins; The Grb family binds to the epidermal growth factor receptor (EGFR, erbB1) via their SH2 domains. There are 3 members of the Grb7 family of proteins: Grb7, Grb10, and Grb14. They are composed of an N-terminal Proline-rich domain, a Ras Associating-like (RA) domain, a Pleckstrin Homology (PH) domain, a phosphotyrosine interaction region (PIR, BPS) and a C-terminal SH2 domain. The SH2 domains of Grb7, Grb10 and Grb14 preferentially bind to a different RTK. Grb7 binds strongly to the erbB2 receptor, unlike Grb10 and Grb14 which bind weakly to it. Grb14 binds to Fibroblast Growth Factor Receptor (FGFR). Grb10 has been shown to interact with many different proteins, including the insulin and IGF1 receptors, platelet-derived growth factor (PDGF) receptor-beta, Ret, Kit, Raf1 and MEK1, and Nedd4. Grb7 family proteins are phosphorylated on serine/threonine as well as tyrosine residues. In general SH2 domains are involved in signal transduction. They typically bind pTyr-containing ligands via two surface pockets, a pTyr and hydrophobic binding pocket, allowing proteins with SH2 domains to localize to tyrosine phosphorylated sites.


Pssm-ID: 198197 [Multi-domain]  Cd Length: 108  Bit Score: 40.10  E-value: 4.44e-04
                        10        20        30        40        50
                ....*....|....*....|....*....|....*....|....*....|....*..
gi 32455248 619 HDEKTWNVGSSNRNKAENLLR--GKRDGTFLVRES-SKQGCYACSVVVDGEVKHCVI 672
Cdd:cd09944   2 HRSQPWFHGGISRDEAARLIRqqGLVDGVFLVRESqSNPGAFVLSLKHGQKIKHYQI 58
SH2_SH2B3 cd10412
Src homology 2 (SH2) domain found in SH2B adapter proteins (SH2B1, SH2B2, SH2B3); SH2B3 (Lnk), ...
333-410 4.45e-04

Src homology 2 (SH2) domain found in SH2B adapter proteins (SH2B1, SH2B2, SH2B3); SH2B3 (Lnk), like other members of the SH2B adapter protein family, contains a pleckstrin homology domain, at least one dimerization domain, and a C-terminal SH2 domain which binds to phosphorylated tyrosines in a variety of tyrosine kinases. SH2B3 negatively regulates lymphopoiesis and early hematopoiesis. The lnk-deficiency results in enhanced production of B cells, and expansion as well as enhanced function of hematopoietic stem cells (HSCs), demonstrating negative regulatory functions of Sh2b3/Lnk in cytokine signaling. Sh2b3/Lnk also functions in responses controlled by cell adhesion and in crosstalk between integrin- and cytokine-mediated signaling. In general SH2 domains are involved in signal transduction. They typically bind pTyr-containing ligands via two surface pockets, a pTyr and hydrophobic binding pocket, allowing proteins with SH2 domains to localize to tyrosine phosphorylated sites.


Pssm-ID: 198275  Cd Length: 97  Bit Score: 39.88  E-value: 4.45e-04
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 32455248 333 WYWGDISREEVNEKLRD---TADGTFLVRDASTKmHGDYTLTLRKGGNNKLIKIFHRDGKYGFSDPLTFSSVVELINHYR 409
Cdd:cd10412  10 WFHGPISRVKAAQLVQLqgpDAHGVFLVRQSETR-RGEYVLTFNFQGRAKHLRLSLTERGQCRVQHLHFPSVVDMLHHFQ 88

                .
gi 32455248 410 N 410
Cdd:cd10412  89 R 89
SH3_SH3RF_3 cd11783
Third Src Homology 3 domain of SH3 domain containing ring finger 1 (SH3RF1), SH3RF3, and ...
8-74 5.33e-04

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: 38.53  E-value: 5.33e-04
                        10        20        30        40        50        60
                ....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 32455248   8 YRALYDYKKEREEDIDLHLGDILTVnkgslvalgFSDGQEarpeeiGWLNGYNETTGERGDFPGTYV 74
Cdd:cd11783   2 YVALYPYKPQKPDELELRKGEMYTV---------TEKCQD------GWFKGTSLRTGQSGVFPGNYV 53
SH2_C-SH2_Zap70 cd10402
C-terminal Src homology 2 (SH2) domain found in Zeta-chain-associated protein kinase 70 ...
333-409 5.42e-04

C-terminal Src homology 2 (SH2) domain found in Zeta-chain-associated protein kinase 70 (ZAP-70); ZAP-70 and Syk comprise a family of hematopoietic cell specific protein tyrosine kinases (PTKs) that are required for antigen and antibody receptor function. ZAP-70 is expressed in T and natural killer (NK) cells and Syk is expressed in B cells, mast cells, polymorphonuclear leukocytes, platelets, macrophages, and immature T cells. They are required for the proper development of T and B cells, immune receptors, and activating NK cells. They consist of two N-terminal Src homology 2 (SH2) domains and a C-terminal kinase domain separated from the SH2 domains by a linker or hinge region. Phosphorylation of both tyrosine residues within the Immunoreceptor Tyrosine-based Activation Motifs (ITAM; consensus sequence Yxx[LI]x(7,8)Yxx[LI]) by the Src-family PTKs is required for efficient interaction of ZAP-70 and Syk with the receptor subunits and for receptor function. ZAP-70 forms two phosphotyrosine binding pockets, one of which is shared by both SH2 domains. In Syk the two SH2 domains do not form such a phosphotyrosine-binding site. The SH2 domains here are believed to function independently. In addition, the two SH2 domains of Syk display flexibility in their relative orientation, allowing Syk to accommodate a greater variety of spacing sequences between the ITAM phosphotyrosines and singly phosphorylated non-classical ITAM ligands. This model contains the C-terminus SH2 domains of Zap70. In general SH2 domains are involved in signal transduction. They typically bind pTyr-containing ligands via two surface pockets, a pTyr and hydrophobic binding pocket, allowing proteins with SH2 domains to localize to tyrosine phosphorylated sites.


Pssm-ID: 198265  Cd Length: 105  Bit Score: 39.90  E-value: 5.42e-04
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 32455248 333 WYWGDISREEVNEKLRDTA--DGTFLVRDasTKMHGDYTLTLRKGGNNKLIKIFH-RDGKYGFSDPLTFSSVVELINHYR 409
Cdd:cd10402  12 WYHGSIARDEAERRLYSGAqpDGKFLLRE--RKESGTYALSLVYGKTVYHYRIDQdKSGKYSIPEGTKFDTLWQLVEYLK 89
SH2_Src_Fyn cd10368
Src homology 2 (SH2) domain found in Fyn; Fyn is a member of the Src non-receptor type ...
622-702 5.49e-04

Src homology 2 (SH2) domain found in Fyn; Fyn is a member of the Src non-receptor type tyrosine kinase family of proteins. Fyn is involved in the control of cell growth and is required in the following pathways: T and B cell receptor signaling, integrin-mediated signaling, growth factor and cytokine receptor signaling, platelet activation, ion channel function, cell adhesion, axon guidance, fertilization, entry into mitosis, and differentiation of natural killer cells, oligodendrocytes and keratinocytes. The protein associates with the p85 subunit of phosphatidylinositol 3-kinase and interacts with the Fyn-binding protein. Alternatively spliced transcript variants encoding distinct isoforms exist. Fyn is primarily localized to the cytoplasmic leaflet of the plasma membrane. Tyrosine phosphorylation of target proteins by Fyn serves to either regulate target protein activity, and/or to generate a binding site on the target protein that recruits other signaling molecules. FYN has been shown to interact with a number of proteins including: BCAR1, Cbl, Janus kinase, nephrin, Sky, tyrosine kinase, Wiskott-Aldrich syndrome protein, and Zap-70. Fyn has a unique N-terminal domain, an SH3 domain, an SH2 domain, a kinase domain and a regulatory tail, as do the other members of the family. In general SH2 domains are involved in signal transduction. They typically bind pTyr-containing ligands via two surface pockets, a pTyr and hydrophobic binding pocket, allowing proteins with SH2 domains to localize to tyrosine phosphorylated sites.


Pssm-ID: 198231 [Multi-domain]  Cd Length: 101  Bit Score: 40.01  E-value: 5.49e-04
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 32455248 622 KTWNVGSSNRNKAENLLR--GKRDGTFLVRES-SKQGCYACSV-----VVDGEVKHCVINKTATGYGFAEPYNLYSSLKE 693
Cdd:cd10368   3 EEWYFGKLGRKDAERQLLsfGNPRGTFLIRESeTTKGAYSLSIrdwddMKGDHVKHYKIRKLDNGGYYITTRAQFETLQQ 82

                ....*....
gi 32455248 694 LVLHYQHTS 702
Cdd:cd10368  83 LVQHYSETA 91
SH2_Src_Blk cd10371
Src homology 2 (SH2) domain found in B lymphoid kinase (Blk); Blk is a member of the Src ...
624-717 7.17e-04

Src homology 2 (SH2) domain found in B lymphoid kinase (Blk); Blk is a member of the Src non-receptor type tyrosine kinase family of proteins. Blk is expressed in the B-cells. Unlike most other Src members Blk lacks cysteine residues in the SH4 domain that undergo palmitylation. Blk is required for the development of IL-17-producing gamma-delta T cells. Furthermore, Blk is expressed in lymphoid precursors and, in this capacity, plays a role in regulating thymus cellularity during ontogeny. Blk has a unique N-terminal domain, an SH3 domain, an SH2 domain, a kinase domain and a regulatory tail, as do the other members of the family. In general SH2 domains are involved in signal transduction. They typically bind pTyr-containing ligands via two surface pockets, a pTyr and hydrophobic binding pocket, allowing proteins with SH2 domains to localize to tyrosine phosphorylated sites.


Pssm-ID: 198234 [Multi-domain]  Cd Length: 100  Bit Score: 39.62  E-value: 7.17e-04
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 32455248 624 WNVGSSNRNKAENLLRG--KRDGTFLVRES-SKQGCYACSV---VVDGEV-KHCVINKTATGYGFAEPYNLYSSLKELVL 696
Cdd:cd10371   5 WFFRTISRKDAERQLLApmNKAGSFLIRESeSNKGAFSLSVkdvTTQGEVvKHYKIRSLDNGGYYISPRITFPTLQALVQ 84
                        90       100
                ....*....|....*....|.
gi 32455248 697 HYQhtslvQHNDSLNVTLAYP 717
Cdd:cd10371  85 HYS-----KKGDGLCQKLTLP 100
SH2_Nck_family cd09943
Src homology 2 (SH2) domain found in the Nck family; Nck proteins are adaptors that modulate ...
622-699 7.53e-04

Src homology 2 (SH2) domain found in the Nck family; Nck proteins are adaptors that modulate actin cytoskeleton dynamics by linking proline-rich effector molecules to tyrosine kinases or phosphorylated signaling intermediates. There are two members known in this family: Nck1 (Nckalpha) and Nck2 (Nckbeta and Growth factor receptor-bound protein 4 (Grb4)). They are characterized by having 3 SH3 domains and a C-terminal SH2 domain. Nck1 and Nck2 have overlapping functions as determined by gene knockouts. Both bind receptor tyrosine kinases and other tyrosine-phosphorylated proteins through their SH2 domains. In addition they also bind distinct targets. Neuronal signaling proteins: EphrinB1, EphrinB2, and Disabled-1 (Dab-1) all bind to Nck-2 exclusively. And in the case of PDGFR, Tyr(P)751 binds to Nck1 while Tyr(P)1009 binds to Nck2. Nck1 and Nck2 have a role in the infection process of enteropathogenic Escherichia coli (EPEC). Their SH3 domains are involved in recruiting and activating the N-WASP/Arp2/3 complex inducing actin polymerization resulting in the production of pedestals, dynamic bacteria-presenting protrusions of the plasma membrane. A similar thing occurs in the vaccinia virus where motile plasma membrane projections are formed beneath the virus. Recently it has been shown that the SH2 domains of both Nck1 and Nck2 bind the G-protein coupled receptor kinase-interacting protein 1 (GIT1) in a phosphorylation-dependent manner. In general SH2 domains are involved in signal transduction. They typically bind pTyr-containing ligands via two surface pockets, a pTyr and hydrophobic binding pocket, allowing proteins with SH2 domains to localize to tyrosine phosphorylated sites.


Pssm-ID: 198196  Cd Length: 93  Bit Score: 39.04  E-value: 7.53e-04
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 32455248 622 KTWNVGSSNRNKAENLLRGK-RDGTFLVRES-SKQGCYACSVVVDGEVKHCVINKTATGYGFAEpyNLYSSLKELVLHYQ 699
Cdd:cd09943   1 QPWYYGRITRHQAETLLNEHgHEGDFLIRDSeSNPGDYSVSLKAPGRNKHFKVQVVDNVYCIGQ--RKFHTMDELVEHYK 78
SH2_Src_Fyn_isoform_a_like cd10418
Src homology 2 (SH2) domain found in Fyn isoform a like proteins; Fyn is a member of the Src ...
622-698 7.57e-04

Src homology 2 (SH2) domain found in Fyn isoform a like proteins; Fyn is a member of the Src non-receptor type tyrosine kinase family of proteins. This cd contains the SH2 domain found in Fyn isoform a type proteins. Fyn is involved in the control of cell growth and is required in the following pathways: T and B cell receptor signaling, integrin-mediated signaling, growth factor and cytokine receptor signaling, platelet activation, ion channel function, cell adhesion, axon guidance, fertilization, entry into mitosis, and differentiation of natural killer cells, oligodendrocytes and keratinocytes. The protein associates with the p85 subunit of phosphatidylinositol 3-kinase and interacts with the Fyn-binding protein. Alternatively spliced transcript variants encoding distinct isoforms exist. Fyn is primarily localized to the cytoplasmic leaflet of the plasma membrane. Tyrosine phosphorylation of target proteins by Fyn serves to either regulate target protein activity, and/or to generate a binding site on the target protein that recruits other signaling molecules. FYN has been shown to interact with a number of proteins including: BCAR1, Cbl, Janus kinase, nephrin, Sky, tyrosine kinase, Wiskott-Aldrich syndrome protein, and Zap-70. Fyn has a unique N-terminal domain, an SH3 domain, an SH2 domain, a kinase domain and a regulatory tail, as do the other members of the family. In general SH2 domains are involved in signal transduction. They typically bind pTyr-containing ligands via two surface pockets, a pTyr and hydrophobic binding pocket, allowing proteins with SH2 domains to localize to tyrosine phosphorylated sites.


Pssm-ID: 198281  Cd Length: 101  Bit Score: 39.60  E-value: 7.57e-04
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 32455248 622 KTWNVGSSNRNKAEN--LLRGKRDGTFLVRES-SKQGCYACSV-----VVDGEVKHCVINKTATGYGFAEPYNLYSSLKE 693
Cdd:cd10418   3 EEWYFGKLGRKDAERqlLSFGNPRGTFLIRESeTTKGAYSLSIrdwddMKGDHVKHYKIRKLDNGGYYITTRAQFETLQQ 82

                ....*
gi 32455248 694 LVLHY 698
Cdd:cd10418  83 LVQHY 87
SH2_Tensin_like cd09927
Src homology 2 domain found in Tensin-like proteins; SH2 domain found in Tensin-like proteins. ...
621-701 7.90e-04

Src homology 2 domain found in Tensin-like proteins; SH2 domain found in Tensin-like proteins. The Tensins are a family of intracellular proteins that interact with receptor tyrosine kinases (RTKs), integrins, and actin. They are thought act as signaling bridges between the extracellular space and the cytoskeleton. There are four homologues: Tensin1, Tensin2 (TENC1, C1-TEN), Tensin3 and Tensin4 (cten), all of which contain a C-terminal tandem SH2-PTB domain pairing, as well as actin-binding regions that may localize them to focal adhesions. The isoforms of Tensin2 and Tensin3 contain N-terminal C1 domains, which are atypical and not expected to bind to phorbol esters. Tensins 1-3 contain a phosphatase (PTPase) and C2 domain pairing which resembles PTEN (phosphatase and tensin homologue deleted on chromosome 10) protein. PTEN is a lipid phosphatase that dephosphorylates phosphatidylinositol 3,4,5-trisphosphate (PtdIns(3,4,5)P3) to yield phosphatidylinositol 4,5-bisphosphate (PtdIns(4,5)P2). As PtdIns(3,4,5)P3 is the product of phosphatidylinositol 3-kinase (PI3K) activity, PTEN is therefore a key negative regulator of the PI3K pathway. Because of their PTEN-like domains, the Tensins may also possess phosphoinositide-binding or phosphatase capabilities. However, only Tensin2 and Tensin3 have the potential to be phosphatases since only their PTPase domains contain a cysteine residue that is essential for catalytic activity. In general SH2 domains are involved in signal transduction. They typically bind pTyr-containing ligands via two surface pockets, a pTyr and hydrophobic binding pocket, allowing proteins with SH2 domains to localize to tyrosine phosphorylated sites.


Pssm-ID: 198181 [Multi-domain]  Cd Length: 116  Bit Score: 39.72  E-value: 7.90e-04
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 32455248 621 EKTWNVGSSNRNKAENLLRGKRDGTFLVRES-SKQGCYACSVVVDGE-----------------VKHCVINKTATGY--- 679
Cdd:cd09927   2 SKYWYKPNISRDQAIALLKDKPPGTFLVRDStTYKGAYGLAVKVATPppgvnpfeakgdpeselVRHFLIEPSPKGVklk 81
                        90       100
                ....*....|....*....|...
gi 32455248 680 GFA-EPYnlYSSLKELVlhYQHT 701
Cdd:cd09927  82 GCPnEPV--FGSLSALV--YQHS 100
SH2_C-SH2_Syk_like cd10401
C-terminal Src homology 2 (SH2) domain found in Spleen tyrosine kinase (Syk) proteins; ZAP-70 ...
624-700 9.14e-04

C-terminal Src homology 2 (SH2) domain found in Spleen tyrosine kinase (Syk) proteins; ZAP-70 and Syk comprise a family of hematopoietic cell specific protein tyrosine kinases (PTKs) that are required for antigen and antibody receptor function. ZAP-70 is expressed in T and natural killer (NK) cells and Syk is expressed in B cells, mast cells, polymorphonuclear leukocytes, platelets, macrophages, and immature T cells. They are required for the proper development of T and B cells, immune receptors, and activating NK cells. They consist of two N-terminal Src homology 2 (SH2) domains and a C-terminal kinase domain separated from the SH2 domains by a linker or hinge region. Phosphorylation of both tyrosine residues within the Immunoreceptor Tyrosine-based Activation Motifs (ITAM; consensus sequence Yxx[LI]x(7,8)Yxx[LI]) by the Src-family PTKs is required for efficient interaction of ZAP-70 and Syk with the receptor subunits and for receptor function. ZAP-70 forms two phosphotyrosine binding pockets, one of which is shared by both SH2 domains. In Syk the two SH2 domains do not form such a phosphotyrosine-binding site. The SH2 domains here are believed to function independently. In addition, the two SH2 domains of Syk display flexibility in their relative orientation, allowing Syk to accommodate a greater variety of spacing sequences between the ITAM phosphotyrosines and singly phosphorylated non-classical ITAM ligands. This model contains the C-terminus SH2 domains of Syk. In general SH2 domains are involved in signal transduction. They typically bind pTyr-containing ligands via two surface pockets, a pTyr and hydrophobic binding pocket, allowing proteins with SH2 domains to localize to tyrosine phosphorylated sites.


Pssm-ID: 198264  Cd Length: 99  Bit Score: 39.10  E-value: 9.14e-04
                        10        20        30        40        50        60        70
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 32455248 624 WNVGSSNRNKAEN-LLRGKR-DGTFLVRESSKQGCYACSVVVDGEVKHCVINKTATGYGFAEPYNLYSSLKELVLHYQH 700
Cdd:cd10401   5 WFHGKISREESEQiLLIGSKtNGKFLIRERDNNGSYALCLLHDGKVLHYRIDKDKTGKLSIPDGKKFDTLWQLVEHYSY 83
SH2_Src_Yes cd10366
Src homology 2 (SH2) domain found in Yes; Yes is a member of the Src non-receptor type ...
329-408 9.36e-04

Src homology 2 (SH2) domain found in Yes; Yes is a member of the Src non-receptor type tyrosine kinase family of proteins. Yes is the cellular homolog of the Yamaguchi sarcoma virus oncogene. In humans it is encoded by the YES1 gene which maps to chromosome 18 and is in close proximity to thymidylate synthase. A corresponding Yes pseudogene has been found on chromosome 22. YES1 has been shown to interact with Janus kinase 2, CTNND1,RPL10, and Occludin. Yes1 has a unique N-terminal domain, an SH3 domain, an SH2 domain, a kinase domain and a regulatory tail, as do the other members of the family. In general SH2 domains are involved in signal transduction. They typically bind pTyr-containing ligands via two surface pockets, a pTyr and hydrophobic binding pocket, allowing proteins with SH2 domains to localize to tyrosine phosphorylated sites.


Pssm-ID: 198229  Cd Length: 101  Bit Score: 39.23  E-value: 9.36e-04
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 32455248 329 QDAEWYWGDISREEVNEKLRDTAD--GTFLVRDASTkMHGDYTLTLR-----KGGNNKLIKIFHRD-GKYGFSDPLTFSS 400
Cdd:cd10366   1 QAEEWYFGKMGRKDAERLLLNPGNqrGIFLVRESET-TKGAYSLSIRdwdevRGDNVKHYKIRKLDnGGYYITTRAQFDT 79

                ....*...
gi 32455248 401 VVELINHY 408
Cdd:cd10366  80 LQKLVKHY 87
PRK03918 PRK03918
DNA double-strand break repair ATPase Rad50;
430-580 9.71e-04

DNA double-strand break repair ATPase Rad50;


Pssm-ID: 235175 [Multi-domain]  Cd Length: 880  Bit Score: 42.74  E-value: 9.71e-04
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 32455248  430 KYQQDQVVKEDNIEavgKKLHEYNTQFQEKSREYDRLYEEYTRTSQEIQMKRTAIEAFNETIKIFEEQcqtqeRYSKEYI 509
Cdd:PRK03918 179 ERLEKFIKRTENIE---ELIKEKEKELEEVLREINEISSELPELREELEKLEKEVKELEELKEEIEEL-----EKELESL 250
                         90       100       110       120       130       140       150
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|.
gi 32455248  510 EKFKREGNEKeIQRIMHNYDKLKSRISEIIDSRRRLEEdLKKQAAEYREIDKRMNSIKPDLIQLRKTRDQY 580
Cdd:PRK03918 251 EGSKRKLEEK-IRELEERIEELKKEIEELEEKVKELKE-LKEKAEEYIKLSEFYEEYLDELREIEKRLSRL 319
SH2_SHD cd10390
Src homology 2 domain found in SH2 domain-containing adapter proteins D (SHD); The expression ...
624-718 1.06e-03

Src homology 2 domain found in SH2 domain-containing adapter proteins D (SHD); The expression of SHD is restricted to the brain. SHD may be a physiological substrate of c-Abl and may function as an adapter protein in the central nervous system. It is also thought to be involved in apoptotic regulation. SHD contains five YXXP motifs, a substrate sequence preferred by Abl tyrosine kinases, in addition to a poly-proline rich region and a C-terminal SH2 domain. In general SH2 domains are involved in signal transduction. They typically bind pTyr-containing ligands via two surface pockets, a pTyr and hydrophobic binding pocket, allowing proteins with SH2 domains to localize to tyrosine phosphorylated sites.


Pssm-ID: 198253  Cd Length: 98  Bit Score: 38.91  E-value: 1.06e-03
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 32455248 624 WNVGSSNRNKAENLLRGKRDGTFLVR--ESSKQGCyACSVVVDGEVKHCVINKT-ATGYGFAEPYNLYSSLKELVLHYQH 700
Cdd:cd10390   3 WFHGPLSRADAENLLSLCKEGSYLVRlsETRPQDC-SLSLRSSQGFLHLKFARTrENQVVLGQHSGPFPSVPELVLHYSS 81
                        90
                ....*....|....*....
gi 32455248 701 TSL-VQHNDSLnvTLAYPV 718
Cdd:cd10390  82 RPLpVQGAEHL--ALLYPV 98
SH3_PIX cd11877
Src Homology 3 domain of Pak Interactive eXchange factors; PIX proteins are Rho guanine ...
7-76 1.11e-03

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: 37.68  E-value: 1.11e-03
                        10        20        30        40        50        60        70
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 32455248   7 QYRALYDYKKEREEDIDLHLGDILTVNKgslvalgfsdgqearPEEIGWLNGYNEttGERGDFPGTYVEY 76
Cdd:cd11877   1 LVRAKFNFEGTNEDELSFDKGDIITVTQ---------------VVEGGWWEGTLN--GKTGWFPSNYVKE 53
SH2_HSH2_like cd09946
Src homology 2 domain found in hematopoietic SH2 (HSH2) protein; HSH2 is thought to function ...
624-712 1.21e-03

Src homology 2 domain found in hematopoietic SH2 (HSH2) protein; HSH2 is thought to function as an adapter protein involved in tyrosine kinase signaling. It may also be involved in regulating cytokine signaling and cytoskeletal reorganization in hematopoietic cells. HSH2 contains several putative protein-binding motifs, SH3-binding proline-rich regions, and phosphotyrosine sites, but lacks enzymatic motifs. HSH2 was found to interact with cytokine-regulated tyrosine kinase c-FES and an activated Cdc42-associated tyrosine kinase ACK1. HSH2 binds c-FES through both its C-terminal region and its N-terminal region including the SH2 domain and binds ACK1 via its N-terminal proline-rich region. Both kinases bound and tyrosine-phosphorylated HSH2 in mammalian cells. In general SH2 domains are involved in signal transduction. They typically bind pTyr-containing ligands via two surface pockets, a pTyr and hydrophobic binding pocket, allowing proteins with SH2 domains to localize to tyrosine phosphorylated sites.


Pssm-ID: 198199  Cd Length: 102  Bit Score: 38.72  E-value: 1.21e-03
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 32455248 624 WNVGSSNRNKAENLLRGKRDGTFLVRESSKQGCYACSVVVDGEVKHCVINKTATG-YGFAEPYNLYSSLKELVLHYQHTS 702
Cdd:cd09946   9 WFHGAISREAAENMLESQPLGSFLIRVSHSHVGYTLSYKAQSSCRHFMVKLLDDGtFMIPGEKVAHTSLHALVTFHQQKP 88
                        90
                ....*....|
gi 32455248 703 LVQHNDSLNV 712
Cdd:cd09946  89 IEPRRELLTQ 98
SH2_SHE cd10391
Src homology 2 domain found in SH2 domain-containing adapter protein E (SHE); SHE is expressed ...
622-718 1.24e-03

Src homology 2 domain found in SH2 domain-containing adapter protein E (SHE); SHE is expressed in heart, lung, brain, and skeletal muscle. SHE contains two pTry protein binding domains, protein interaction domain (PID) and a SH2 domain, followed by a glycine-proline rich region, all of which are N-terminal to the phosphotyrosine binding (PTB) domain. In general SH2 domains are involved in signal transduction. They typically bind pTyr-containing ligands via two surface pockets, a pTyr and hydrophobic binding pocket, allowing proteins with SH2 domains to localize to tyrosine phosphorylated sites.


Pssm-ID: 198254  Cd Length: 98  Bit Score: 38.78  E-value: 1.24e-03
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 32455248 622 KTWNVGSSNRNKAENLLRGKRDGTFLVRES-SKQGCYACSVVVDGEVKHCVINKTA-TGYGFAEPYNLYSSLKElVLHYQ 699
Cdd:cd10391   1 QPWYHGSISRAEAESRLQPCKEASYLVRNSeSGNSKYSIALKTSQGCVHIIVAQTKdNKYTLNQTSAVFDSIPE-VVHYY 79
                        90
                ....*....|....*....
gi 32455248 700 HTSLVQHNDSLNVTLAYPV 718
Cdd:cd10391  80 SNEKLPFKGAEHMTLLHPV 98
SH3_CD2AP-like_1 cd11873
First Src Homology 3 domain (SH3A) of CD2-associated protein and similar proteins; This ...
8-75 1.31e-03

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: 37.25  E-value: 1.31e-03
                        10        20        30        40        50        60
                ....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 32455248   8 YRALYDYKKEREEDIDLHLGDILTvnkgslvalgfsdgqEARPEEIGWLNGynETTGERGDFPGTYVE 75
Cdd:cd11873   2 VIVEFDYDAEEPDELTLKVGDIIT---------------NVKKMEEGWWEG--TLNGKRGMFPDNFVK 52
PRK03918 PRK03918
DNA double-strand break repair ATPase Rad50;
440-575 1.43e-03

DNA double-strand break repair ATPase Rad50;


Pssm-ID: 235175 [Multi-domain]  Cd Length: 880  Bit Score: 41.97  E-value: 1.43e-03
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 32455248  440 DNIEAVGKKLHEYNTQ-FQEKSREYDRLYEEYTRTSQEIQMKRTAIEAFNETIK---IFEEQCQTQERYSKEYIEKFKRE 515
Cdd:PRK03918 503 EQLKELEEKLKKYNLEeLEKKAEEYEKLKEKLIKLKGEIKSLKKELEKLEELKKklaELEKKLDELEEELAELLKELEEL 582
                         90       100       110       120       130       140       150
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|..
gi 32455248  516 GNE---------KEIQRIMHNYDKLK---SRISEIIDSRRRLEEDLKKQAAEYREIDKRMNSIKPDLIQLRK 575
Cdd:PRK03918 583 GFEsveeleerlKELEPFYNEYLELKdaeKELEREEKELKKLEEELDKAFEELAETEKRLEELRKELEELEK 654
SH2_Jak3 cd10380
Src homology 2 (SH2) domain in the Janus kinase 3 (Jak3) proteins; Jak3 is a member of the ...
640-699 1.44e-03

Src homology 2 (SH2) domain in the Janus kinase 3 (Jak3) proteins; Jak3 is a member of the Janus kinase (JAK) family of tyrosine kinases involved in cytokine receptor-mediated intracellular signal transduction. It is predominantly expressed in immune cells and transduces a signal in response to its activation via tyrosine phosphorylation by interleukin receptors. Mutations in this gene are associated with autosomal SCID (severe combined immunodeficiency disease). In general SH2 domains are involved in signal transduction. They typically bind pTyr-containing ligands via two surface pockets, a pTyr and hydrophobic binding pocket, allowing proteins with SH2 domains to localize to tyrosine phosphorylated sites.


Pssm-ID: 198243  Cd Length: 96  Bit Score: 38.61  E-value: 1.44e-03
                        10        20        30        40        50        60
                ....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 32455248 640 GKRDGTFLVRESSKQ-GCYACSVVVDG----EVKHCVINKTATGYGFAEPYNLYSSLKELVLHYQ 699
Cdd:cd10380  32 GSEPGSFVLRRSPQDfDKFLLTVCVQTtlglDYKDCLIRKNEGHFSLAGVSRSFSSLKELLVTYQ 96
SH3_Nebulin_C cd11933
C-terminal Src Homology 3 domain of Nebulin; Nebulin is a giant filamentous protein (600-900 ...
5-77 1.47e-03

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: 37.29  E-value: 1.47e-03
                        10        20        30        40        50        60        70
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|...
gi 32455248   5 GYQYRALYDYKKEREEDIDLHLGDILtVNKGSLvalgfsdgqearpeEIGWLNGYNETTGERGDFPGTYVEYI 77
Cdd:cd11933   1 GKSFRAMYDYRAADDDEVSFKDGDTI-VNVQTI--------------DEGWMYGTVQRTGKTGMLPANYVEAI 58
SH3_SNX33 cd11896
Src Homology 3 domain of Sorting Nexin 33; SNX33 interacts with Wiskott-Aldrich syndrome ...
9-75 1.48e-03

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: 37.25  E-value: 1.48e-03
                        10        20        30        40        50        60
                ....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 32455248   9 RALYDYKKEREEDIDLHLGDILTVnkgslvalgFSDGQEArpeeiGWLNGYNeTTGERGDFPGTYVE 75
Cdd:cd11896   3 RALYSFQSENKEEINIQENEELVI---------FSENSLD-----GWLQGQN-SRGETGLFPASYVE 54
SH2_Tec_Txk cd10398
Src homology 2 (SH2) domain found in Tec protein, Txk; A member of the Tec protein tyrosine ...
327-428 1.63e-03

Src homology 2 (SH2) domain found in Tec protein, Txk; A member of the Tec protein tyrosine kinase Txk is expressed in thymus, spleen, lymph node, T lymphocytes, NK cells, mast cell lines, and myeloid cell line. Txk plays a role in TCR signal transduction, T cell development, and selection which is analogous to the function of Itk. Txk has been shown to interact with IFN-gamma. Unlike most of the Tec family members Txk lacks a PH domain. Instead Txk has a unique region containing a palmitoylated cysteine string which has a similar membrane tethering function as the PH domain. Txk also has a zinc-binding motif, a SH3 domain, a SH2 domain, and a protein kinase catalytic domain. The TH domain consists of a Zn2+-binding Btk motif and a proline-rich region. The Btk motif is found in Tec kinases, Ras GAP, and IGBP and crucial to the function of the PH domain. It is not present in Txk which is not surprising since it lacks a PH domain. The type 1 splice form of the Drosophila homolog also lacks both the PH domain and the Btk motif. The proline-rich regions are highly conserved for the most part with the exception of Bmx whose residues surrounding the PXXP motif are not conserved (TH-like) and Btk29A which is entirely unique with large numbers of glycine residues (TH-extended). Tec family members all lack a C-terminal tyrosine having an autoinhibitory function in its phosphorylated state. In general SH2 domains are involved in signal transduction. They typically bind pTyr-containing ligands via two surface pockets, a pTyr and hydrophobic binding pocket, allowing proteins with SH2 domains to localize to tyrosine phosphorylated sites.


Pssm-ID: 198261  Cd Length: 106  Bit Score: 38.77  E-value: 1.63e-03
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 32455248 327 SLQDAEWYWGDISREEVNEKLRDTA-DGTFLVRDASTKmhGDYTLTL------RKGGNNKLIKIFHRD-GKYGFSDPLTF 398
Cdd:cd10398   2 NLEIYEWYHKNITRNQAERLLRQESkEGAFIVRDSRHL--GSYTISVftrarrSTEASIKHYQIKKNDsGQWYVAERHLF 79
                        90       100       110
                ....*....|....*....|....*....|.
gi 32455248 399 SSVVELINHYrneslaQYNPK-LDVKLLYPV 428
Cdd:cd10398  80 QSIPELIQYH------QHNAAgLMSRLRYPV 104
SH3_CD2AP-like_3 cd11875
Third Src Homology 3 domain (SH3C) of CD2-associated protein and similar proteins; This ...
7-75 1.66e-03

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: 36.94  E-value: 1.66e-03
                        10        20        30        40        50        60        70
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 32455248   7 QYRALYDYKKEREEDIDLHLGDILTV-NKGSlvalgfsdgqearpEEIGWLNGynETTGERGDFPGTYVE 75
Cdd:cd11875   1 KARVLFDYEAENEDELTLREGDIVTIlSKDC--------------EDKGWWKG--ELNGKRGVFPDNFVE 54
SH3_SH3RF3_3 cd11925
Third Src Homology 3 domain of SH3 domain containing ring finger 3, an E3 ubiquitin-protein ...
8-74 2.02e-03

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: 36.90  E-value: 2.02e-03
                        10        20        30        40        50        60
                ....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 32455248   8 YRALYDYKKEREEDIDLHLGDILTVNKGSlvalgfsdgqearpeEIGWLNGYNETTGERGDFPGTYV 74
Cdd:cd11925   3 YLALYAYKPQKNDELELRKGEMYRVIEKC---------------QDGWFKGTSLRTGVSGVFPGNYV 54
SH2_SH2D7 cd10417
Src homology 2 domain found in the SH2 domain containing protein 7 (SH2D7); SH2D7 contains a ...
333-420 2.27e-03

Src homology 2 domain found in the SH2 domain containing protein 7 (SH2D7); SH2D7 contains a single SH2 domain. In general SH2 domains are involved in signal transduction. They typically bind pTyr-containing ligands via two surface pockets, a pTyr and hydrophobic binding pocket, allowing proteins with SH2 domains to localize to tyrosine phosphorylated sites.


Pssm-ID: 199832  Cd Length: 102  Bit Score: 37.95  E-value: 2.27e-03
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 32455248 333 WYWGDISREEVNEKLRDTADGTFLVRDASTKMhgDYTLTLRKGGNNKLIKIFH-RDGKYGFS-DPLTFSSVVELINHYRN 410
Cdd:cd10417   9 WFHGFITRKQTEQLLRDKALGSFLIRLSDRAT--GYILSYRGSDRCRHFVINQlRNRRYLISgDTSSHSTLAELVRHYQE 86
                        90
                ....*....|
gi 32455248 411 ESLAQYNPKL 420
Cdd:cd10417  87 VQLEPFGETL 96
SH3_1 pfam00018
SH3 domain; SH3 (Src homology 3) domains are often indicative of a protein involved in signal ...
9-70 3.06e-03

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: 36.03  E-value: 3.06e-03
                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|..
gi 32455248     9 RALYDYKKEREEDIDLHLGDILTVnkgslvaLGFSDGqearpeeiGWLNGYNeTTGERGDFP 70
Cdd:pfam00018   1 VALYDYTAQEPDELSFKKGDIIIV-------LEKSED--------GWWKGRN-KGGKEGLIP 46
PRK03918 PRK03918
DNA double-strand break repair ATPase Rad50;
438-577 3.10e-03

DNA double-strand break repair ATPase Rad50;


Pssm-ID: 235175 [Multi-domain]  Cd Length: 880  Bit Score: 40.82  E-value: 3.10e-03
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 32455248  438 KEDNIEAVGKKLHEYNTQFQEKSREYDRL---YEEYTRTSQEIQMKRTAIEAFNETIKIFEEQCQTQERYSKEYIEKFK- 513
Cdd:PRK03918 198 KEKELEEVLREINEISSELPELREELEKLekeVKELEELKEEIEELEKELESLEGSKRKLEEKIRELEERIEELKKEIEe 277
                         90       100       110       120       130       140
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 32455248  514 ---REGNEKEIQRIMHNYDKLKSRISEIIDSRRRLEEDLKKQAAEYREIDKRMNSIKPDLIQLRKTR 577
Cdd:PRK03918 278 leeKVKELKELKEKAEEYIKLSEFYEEYLDELREIEKRLSRLEEEINGIEERIKELEEKEERLEELK 344
SH2_SH3BP2 cd10359
Src homology 2 domain found in c-Abl SH3 domain-binding protein-2 (SH3BP2); The adaptor ...
351-408 3.15e-03

Src homology 2 domain found in c-Abl SH3 domain-binding protein-2 (SH3BP2); The adaptor protein 3BP2/SH3BP2 plays a regulatory role in signaling from immunoreceptors. The protein-tyrosine kinase Syk phosphorylates 3BP2 which results in the activation of Rac1 through the interaction with the SH2 domain of Vav1 and induces the binding to the SH2 domain of the upstream protein-tyrosine kinase Lyn and enhances its kinase activity. 3BP2 has a positive regulatory role in IgE-mediated mast cell activation. In lymphocytes, engagement of T cell or B cell receptors triggers tyrosine phosphorylation of 3BP2. Suppression of the 3BP2 expression by siRNA results in the inhibition of T cell or B cell receptor-mediated activation of NFAT. 3BP2 is required for the proliferation of B cells and B cell receptor signaling. Mutations in the 3BP2 gene are responsible for cherubism resulting in excessive bone resorption in the jaw. In general SH2 domains are involved in signal transduction. They typically bind pTyr-containing ligands via two surface pockets, a pTyr and hydrophobic binding pocket, allowing proteins with SH2 domains to localize to tyrosine phosphorylated sites.


Pssm-ID: 198222  Cd Length: 101  Bit Score: 37.65  E-value: 3.15e-03
                        10        20        30        40        50        60
                ....*....|....*....|....*....|....*....|....*....|....*....|
gi 32455248 351 ADGTFLVRDASTKmhGDYTLTLRKGGNNKLIK--IFHRDGKYGFSDPLTFSSVVELINHY 408
Cdd:cd10359  26 QDGLYCIRNSSTK--GGKVLVVWDGGAEKVRNyrIFEKDCKFYLHEREVFSSLGSLVEHY 83
SH2_Src_Yes cd10366
Src homology 2 (SH2) domain found in Yes; Yes is a member of the Src non-receptor type ...
624-710 3.41e-03

Src homology 2 (SH2) domain found in Yes; Yes is a member of the Src non-receptor type tyrosine kinase family of proteins. Yes is the cellular homolog of the Yamaguchi sarcoma virus oncogene. In humans it is encoded by the YES1 gene which maps to chromosome 18 and is in close proximity to thymidylate synthase. A corresponding Yes pseudogene has been found on chromosome 22. YES1 has been shown to interact with Janus kinase 2, CTNND1,RPL10, and Occludin. Yes1 has a unique N-terminal domain, an SH3 domain, an SH2 domain, a kinase domain and a regulatory tail, as do the other members of the family. In general SH2 domains are involved in signal transduction. They typically bind pTyr-containing ligands via two surface pockets, a pTyr and hydrophobic binding pocket, allowing proteins with SH2 domains to localize to tyrosine phosphorylated sites.


Pssm-ID: 198229  Cd Length: 101  Bit Score: 37.69  E-value: 3.41e-03
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 32455248 624 WNVGSSNRNKAENLL--RGKRDGTFLVRES-SKQGCYACSV-----VVDGEVKHCVINKTATGYGFAEPYNLYSSLKELV 695
Cdd:cd10366   5 WYFGKMGRKDAERLLlnPGNQRGIFLVRESeTTKGAYSLSIrdwdeVRGDNVKHYKIRKLDNGGYYITTRAQFDTLQKLV 84
                        90
                ....*....|....*
gi 32455248 696 LHYqhtslVQHNDSL 710
Cdd:cd10366  85 KHY-----TEHADGL 94
SH2_SH2D4A cd10350
Src homology 2 domain found in the SH2 domain containing protein 4A (SH2D4A); SH2D4A contains ...
331-427 4.05e-03

Src homology 2 domain found in the SH2 domain containing protein 4A (SH2D4A); SH2D4A contains a single SH2 domain. In general SH2 domains are involved in signal transduction. They typically bind pTyr-containing ligands via two surface pockets, a pTyr and hydrophobic binding pocket, allowing proteins with SH2 domains to localize to tyrosine phosphorylated sites.


Pssm-ID: 198213  Cd Length: 103  Bit Score: 37.60  E-value: 4.05e-03
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 32455248 331 AEWYWGDISREEVNEKLRDTADGTFLVRdASTKMHGdYTLTLRKGGNNKLIKIFHRDGKYGF--SDPLTFSSVVELINHY 408
Cdd:cd10350   7 APWFHGILTLKKANELLLSTMPGSFLIR-VSEKIKG-YALSYLSEEGCKHFLIDASADSYSFlgVDQLQHATLADLVEYH 84
                        90
                ....*....|....*....
gi 32455248 409 RNESLAQYNPKLdvkLLYP 427
Cdd:cd10350  85 KEEPITSLGKEL---LLYP 100
SH2_SHB cd10389
Src homology 2 domain found in SH2 domain-containing adapter protein B (SHB); SHB functions in ...
622-718 4.19e-03

Src homology 2 domain found in SH2 domain-containing adapter protein B (SHB); SHB functions in generating signaling compounds in response to tyrosine kinase activation. SHB contains proline-rich motifs, a phosphotyrosine binding (PTB) domain, tyrosine phosphorylation sites, and a SH2 domain. SHB mediates certain aspects of platelet-derived growth factor (PDGF) receptor-, fibroblast growth factor (FGF) receptor-, neural growth factor (NGF) receptor TRKA-, T cell receptor-, interleukin-2 (IL-2) receptor- and focal adhesion kinase- (FAK) signaling. SRC-like FYN-Related Kinase FRK/RAK (also named BSK/IYK or GTK) and SHB regulate apoptosis, proliferation and differentiation. SHB promotes apoptosis and is also required for proper mitogenicity, spreading and tubular morphogenesis in endothelial cells. SHB also plays a role in preventing early cavitation of embryoid bodies and reduces differentiation to cells expressing albumin, amylase, insulin and glucagon. SHB is a multifunctional protein that has difference responses in different cells under various conditions. In general SH2 domains are involved in signal transduction. They typically bind pTyr-containing ligands via two surface pockets, a pTyr and hydrophobic binding pocket, allowing proteins with SH2 domains to localize to tyrosine phosphorylated sites.


Pssm-ID: 198252  Cd Length: 97  Bit Score: 37.38  E-value: 4.19e-03
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 32455248 622 KTWNVGSSNRNKAENLLRGKRDGTFLVRES-SKQGCYACSVVVDGEVKHCVINKTATGYGFAEPYNLYSSLKElVLHYQH 700
Cdd:cd10389   1 QIWYHGAISRGDAENLLRLCKECSYLVRNSqTSKHDYSLSLKSNQGFMHMKLAKTKEKYVLGQNSPPFDSVPE-VIHYYT 79
                        90
                ....*....|....*...
gi 32455248 701 TSLVQHNDSLNVTLAYPV 718
Cdd:cd10389  80 TRKLPIKGAEHLSLLYPV 97
RhoGAP_srGAP cd04383
RhoGAP_srGAP: RhoGAP (GTPase-activator protein [GAP] for Rho-like small GTPases) domain ...
178-274 4.21e-03

RhoGAP_srGAP: RhoGAP (GTPase-activator protein [GAP] for Rho-like small GTPases) domain present in srGAPs. srGAPs are components of the intracellular part of Slit-Robo signalling pathway that is important for axon guidance and cell migration. srGAPs contain an N-terminal FCH domain, a central RhoGAP domain and a C-terminal SH3 domain; this SH3 domain interacts with the intracellular proline-rich-tail of the Roundabout receptor (Robo). This interaction with Robo then activates the rhoGAP domain which in turn inhibits Cdc42 activity. Small GTPases cluster into distinct families, and all act as molecular switches, active in their GTP-bound form but inactive when GDP-bound. The Rho family of GTPases activates effectors involved in a wide variety of developmental processes, including regulation of cytoskeleton formation, cell proliferation and the JNK signaling pathway. GTPases generally have a low intrinsic GTPase hydrolytic activity but there are family-specific groups of GAPs that enhance the rate of GTP hydrolysis by several orders of magnitude.


Pssm-ID: 239848  Cd Length: 188  Bit Score: 38.94  E-value: 4.21e-03
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 32455248 178 DVHVLADAFKRYLLDLPNPVIPAAVYSEMISLApEVQSSEEYIQLLKKLIRSpsIPHQYWLTLQYLLKHFFKLSQTSSKN 257
Cdd:cd04383  71 DINSVAGVLKLYFRGLENPLFPKERFEDLMSCV-KLENPTERVHQIREILST--LPRSVIIVMRYLFAFLNHLSQFSDEN 147
                        90
                ....*....|....*..
gi 32455248 258 LLNARVLSEIFSPMLFR 274
Cdd:cd04383 148 MMDPYNLAICFGPTLMP 164
SH3_Irsp53_BAIAP2L cd11779
Src Homology 3 domain of Insulin Receptor tyrosine kinase Substrate p53, Brain-specific ...
9-75 4.44e-03

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: 35.76  E-value: 4.44e-03
                        10        20        30        40        50        60
                ....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 32455248   9 RALYDYKKEREEDIDLHLGDILTVnkgslvaLGfsdgqearPEEI-GWLNGYNETTGERGDFPGTYVE 75
Cdd:cd11779   4 KALYPHAAGGETQLSFEEGDVITL-------LG--------PEPRdGWHYGENERSGRRGWFPIAYTE 56
YhaN COG4717
Uncharacterized conserved protein YhaN, contains AAA domain [Function unknown];
440-597 4.49e-03

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


Pssm-ID: 443752 [Multi-domain]  Cd Length: 641  Bit Score: 40.52  E-value: 4.49e-03
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 32455248 440 DNIEAVGKKLHEYntqfQEKSREYDRLYEEYTRTSQEIQMKRTAIEAFNETIKIFEEQCQTQERYSKeyiekfkREGNEK 519
Cdd:COG4717  71 KELKELEEELKEA----EEKEEEYAELQEELEELEEELEELEAELEELREELEKLEKLLQLLPLYQE-------LEALEA 139
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 32455248 520 EIQRIMHNYDKLKSRISEIIDSRRRLEEdLKKQAAEYR-EIDKRMNSIKPDLI-QLRKTRDQYLMWLTQKGVRQKKLNEW 597
Cdd:COG4717 140 ELAELPERLEELEERLEELRELEEELEE-LEAELAELQeELEELLEQLSLATEeELQDLAEELEELQQRLAELEEELEEA 218
SH3_Intersectin2_1 cd11988
First Src homology 3 domain (or SH3A) of Intersectin-2; Intersectin-2 (ITSN2) is an adaptor ...
8-75 4.76e-03

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: 36.00  E-value: 4.76e-03
                        10        20        30        40        50        60
                ....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 32455248   8 YRALYDYKKEREEDIDLHLGDILTVNkgslvalgfsdgqEARPEEIGWLngYNETTGERGDFPGTYVE 75
Cdd:cd11988   4 YRALYPFEARNHDEMSFNAGDIIQVD-------------EKTVGEPGWL--YGSFQGNFGWFPCNYVE 56
SH3_PSTPIP1 cd11824
Src homology 3 domain of Proline-Serine-Threonine Phosphatase-Interacting Protein 1; PSTPIP1, ...
8-75 4.92e-03

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: 35.81  E-value: 4.92e-03
                        10        20        30        40        50        60
                ....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 32455248   8 YRALYDYKKEREEDIDLHLGDILTVnkgslvalgfsdgqeARPEEIGWLNGynETTGERGDFPGTYVE 75
Cdd:cd11824   2 YSVLYDYTAQEDDELSISKGDVVAV---------------IEKGEDGWWTV--ERNGQKGLVPGTYLE 52
SH2_SH2D4B cd10351
Src homology 2 domain found in the SH2 domain containing protein 4B (SH2D4B); SH2D4B contains ...
624-695 4.92e-03

Src homology 2 domain found in the SH2 domain containing protein 4B (SH2D4B); SH2D4B contains a single SH2 domain. In general SH2 domains are involved in signal transduction. They typically bind pTyr-containing ligands via two surface pockets, a pTyr and hydrophobic binding pocket, allowing proteins with SH2 domains to localize to tyrosine phosphorylated sites.


Pssm-ID: 198214  Cd Length: 103  Bit Score: 37.18  E-value: 4.92e-03
                        10        20        30        40        50        60        70
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 32455248 624 WNVGSSNRNKAENLLRGKRDGTFLVRESSKQGCYACSVVVDGEVKHCVINKTATGYGF--AEPyNLYSSLKELV 695
Cdd:cd10351   9 WFHGIISREEAEALLMNATEGSFLVRVSEKIWGYTLSYRLQSGFKHFLVDASGDFYSFlgVDP-NRHATLTDLI 81
CCDC22 pfam05667
Coiled-coil domain-containing protein 22; Human coiled-coil domain-containing protein 22 ...
442-567 5.41e-03

Coiled-coil domain-containing protein 22; Human coiled-coil domain-containing protein 22 (CCDC22) is involved in regulation of NF-kappa-B signalling; the function may involve association with COMMD8 and a CUL1-dependent E3 ubiquitin ligase complex. It is part of the OMMD/CCDC22/CCDC93 (CCC) complex, which interacts with the multisubunit WASH complex required for endosomal deposition of F-actin and cargo trafficking in conjunction with the retromer. This entry also includes CCDC22 homologs from animals and plants.


Pssm-ID: 461708 [Multi-domain]  Cd Length: 600  Bit Score: 40.01  E-value: 5.41e-03
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 32455248   442 IEAVGKKLHEYNTQFQEKSR----EYDRLYEEYTRTSQEIQMKRTAIEAFNETIKIFEEQCQTQERYSKEYIEKFKREGn 517
Cdd:pfam05667 410 VDASAQRLVELAGQWEKHRVplieEYRALKEAKSNKEDESQRKLEEIKELREKIKEVAEEAKQKEELYKQLVAEYERLP- 488
                          90       100       110       120       130
                  ....*....|....*....|....*....|....*....|....*....|
gi 32455248   518 eKEIQRIMHNydklkSRISEIIDSRRRLEEDLKKQAAEYREIDKRMNSIK 567
Cdd:pfam05667 489 -KDVSRSAYT-----RRILEIVKNIKKQKEEITKILSDTKSLQKEINSLT 532
SMC_prok_A TIGR02169
chromosome segregation protein SMC, primarily archaeal type; SMC (structural maintenance of ...
458-596 5.45e-03

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: 40.05  E-value: 5.45e-03
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 32455248    458 EKSREYDRLYEEYTRTSQEIQMKRTAIEAFNETIKIFEEQCQTQERYSKEYIEKFKRegNEKEI---QRIMHNYDK---- 530
Cdd:TIGR02169  706 ELSQELSDASRKIGEIEKEIEQLEQEEEKLKERLEELEEDLSSLEQEIENVKSELKE--LEARIeelEEDLHKLEEalnd 783
                           90       100       110       120       130       140       150
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 32455248    531 -----LKSRISEIIDSRRRLEEDLKKQAAEYREIDKRMNSIKPDLIQLRKTR----DQYLMWLTQKGVRQKKLNE 596
Cdd:TIGR02169  784 learlSHSRIPEIQAELSKLEEEVSRIEARLREIEQKLNRLTLEKEYLEKEIqelqEQRIDLKEQIKSIEKEIEN 858
SH3_PACSIN cd11843
Src homology 3 domain of Protein kinase C and Casein kinase Substrate in Neurons (PACSIN) ...
9-75 7.20e-03

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: 35.09  E-value: 7.20e-03
                        10        20        30        40        50        60
                ....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 32455248   9 RALYDYKKEREEDIDLHLGDILTvnkgslvALGFSDGQearpeeiGWLNGynETTGERGDFPGTYVE 75
Cdd:cd11843   3 RALYDYEGQESDELSFKAGDILT-------KLEEEDEQ-------GWCKG--RLDGRVGLYPANYVE 53
RhoGAP_ARHGAP19 cd04392
RhoGAP_ARHGAP19: RhoGAP (GTPase-activator protein [GAP] for Rho-like small GTPases) domain of ...
132-272 7.39e-03

RhoGAP_ARHGAP19: RhoGAP (GTPase-activator protein [GAP] for Rho-like small GTPases) domain of ArhGAP19-like proteins. The function of ArhGAP19 is unknown. Small GTPases cluster into distinct families, and all act as molecular switches, active in their GTP-bound form but inactive when GDP-bound. The Rho family of GTPases activates effectors involved in a wide variety of developmental processes, including regulation of cytoskeleton formation, cell proliferation and the JNK signaling pathway. GTPases generally have a low intrinsic GTPase hydrolytic activity but there are family-specific groups of GAPs that enhance the rate of GTP hydrolysis by several orders of magnitude.


Pssm-ID: 239857  Cd Length: 208  Bit Score: 38.60  E-value: 7.39e-03
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 32455248 132 LIKLVEAIEKKgLECSTLYR-TQSSSNLAELRQLLDCDTPsVDLEMIDVHV--LADAFKRYLLDLPNPVIPAAVYSEMIS 208
Cdd:cd04392  13 IYQLIEYLEKN-LRVEGLFRkPGNSARQQELRDLLNSGTD-LDLESGGFHAhdCATVLKGFLGELPEPLLTHAHYPAHLQ 90
                        90       100       110       120       130       140       150
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 32455248 209 LAPEVQSSE--------------EYIQLLKKLIrspsiPHQYWLTLQYLLKHFFKLSQTSSKNLLNARVLSEIFSPML 272
Cdd:cd04392  91 IADLCQFDEkgnktsapdkerllEALQLLLLLL-----PEENRNLLKLILDLLYQTAKHEDKNKMSADNLALLFTPHL 163
Mitofilin pfam09731
Mitochondrial inner membrane protein; Mitofilin controls mitochondrial cristae morphology. ...
464-600 7.68e-03

Mitochondrial inner membrane protein; Mitofilin controls mitochondrial cristae morphology. Mitofilin is enriched in the narrow space between the inner boundary and the outer membranes, where it forms a homotypic interaction and assembles into a large multimeric protein complex. The first 78 amino acids contain a typical amino-terminal-cleavable mitochondrial presequence rich in positive-charged and hydroxylated residues and a membrane anchor domain. In addition, it has three centrally located coiled coil domains.


Pssm-ID: 430783 [Multi-domain]  Cd Length: 618  Bit Score: 39.74  E-value: 7.68e-03
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 32455248   464 DRLYEEYTRTSQEIQMKRT--------AIEAFNETIKIFEEQCQTQERYSKEYIEKFKREGNEKEIQRIMHNYD-KLKS- 533
Cdd:pfam09731 290 AHAHREIDQLSKKLAELKKreekhierALEKQKEELDKLAEELSARLEEVRAADEAQLRLEFEREREEIRESYEeKLRTe 369
                          90       100       110       120       130       140
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 32455248   534 --RISEIIDsrRRLEEDLKKQAAEYREidKRMNSIKPDLiqlrktrdqylmwLTQKGVRQKKLNEWLGN 600
Cdd:pfam09731 370 leRQAEAHE--EHLKDVLVEQEIELQR--EFLQDIKEKV-------------EEERAGRLLKLNELLAN 421
SH2_Src_Fyn_isoform_b_like cd10419
Src homology 2 (SH2) domain found in Fyn isoform b like proteins; Fyn is a member of the Src ...
622-702 7.97e-03

Src homology 2 (SH2) domain found in Fyn isoform b like proteins; Fyn is a member of the Src non-receptor type tyrosine kinase family of proteins. This cd contains the SH2 domain found in Fyn isoform b type proteins. Fyn is involved in the control of cell growth and is required in the following pathways: T and B cell receptor signaling, integrin-mediated signaling, growth factor and cytokine receptor signaling, platelet activation, ion channel function, cell adhesion, axon guidance, fertilization, entry into mitosis, and differentiation of natural killer cells, oligodendrocytes and keratinocytes. The protein associates with the p85 subunit of phosphatidylinositol 3-kinase and interacts with the Fyn-binding protein. Alternatively spliced transcript variants encoding distinct isoforms exist. Fyn is primarily localized to the cytoplasmic leaflet of the plasma membrane. Tyrosine phosphorylation of target proteins by Fyn serves to either regulate target protein activity, and/or to generate a binding site on the target protein that recruits other signaling molecules. FYN has been shown to interact with a number of proteins including: BCAR1, Cbl, Janus kinase, nephrin, Sky, tyrosine kinase, Wiskott-Aldrich syndrome protein, and Zap-70. Fyn has a unique N-terminal domain, an SH3 domain, an SH2 domain, a kinase domain and a regulatory tail, as do the other members of the family. In general SH2 domains are involved in signal transduction. They typically bind pTyr-containing ligands via two surface pockets, a pTyr and hydrophobic binding pocket, allowing proteins with SH2 domains to localize to tyrosine phosphorylated sites.


Pssm-ID: 198282  Cd Length: 101  Bit Score: 36.58  E-value: 7.97e-03
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 32455248 622 KTWNVGSSNRNKAENLLR--GKRDGTFLVRES-SKQGCYACSV-----VVDGEVKHCVINKTATGYGFAEPYNLYSSLKE 693
Cdd:cd10419   3 EEWYFGKLGRKDAERQLLsfGNPRGTFLIRESeTTKGAYSLSIrdwddMKGDHVKHYKIRKLDNGGYYITTRAQFETLQQ 82

                ....*....
gi 32455248 694 LVLHYQHTS 702
Cdd:cd10419  83 LVQHYSEKA 91
SH2_SH2D2A_SH2D7 cd10349
Src homology 2 domain found in the SH2 domain containing protein 2A and 7 (SH2D2A and SH2D7); ...
333-408 8.32e-03

Src homology 2 domain found in the SH2 domain containing protein 2A and 7 (SH2D2A and SH2D7); SH2D2A and SH7 both contain a single SH2 domain. In general SH2 domains are involved in signal transduction. They typically bind pTyr-containing ligands via two surface pockets, a pTyr and hydrophobic binding pocket, allowing proteins with SH2 domains to localize to tyrosine phosphorylated sites.


Pssm-ID: 199830  Cd Length: 77  Bit Score: 35.96  E-value: 8.32e-03
                        10        20        30        40        50        60        70
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 32455248 333 WYWGDISREEVNEKLRDTADGTFLVRDASTKMhgDYTLTLRKGGNNKLIKIFH-RDGKYGFS-DPLTFSSVVELINHY 408
Cdd:cd10349   2 WFHGFITRREAERLLEPKPQGCYLVRFSESAV--TFVLSYRSRTCCRHFLLAQlRDGRHVVLgEDSAHARLQDLLLHY 77
 
Blast search parameters
Data Source: Precalculated data, version = cdd.v.3.21
Preset Options:Database: CDSEARCH/cdd   Low complexity filter: no  Composition Based Adjustment: yes   E-value threshold: 0.01

References:

  • Wang J et al. (2023), "The conserved domain database in 2023", Nucleic Acids Res.51(D)384-8.
  • Lu S et al. (2020), "The conserved domain database in 2020", Nucleic Acids Res.48(D)265-8.
  • Marchler-Bauer A et al. (2017), "CDD/SPARCLE: functional classification of proteins via subfamily domain architectures.", Nucleic Acids Res.45(D)200-3.
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