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Conserved domains on  [gi|115527076|ref|NP_001068567|]
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src kinase-associated phosphoprotein 1 isoform 2 [Homo sapiens]

Protein Classification

PH_Skap1 and SH3_SKAP1 domain-containing protein( domain architecture ID 10194040)

PH_Skap1 and SH3_SKAP1 domain-containing protein

Graphical summary

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List of domain hits

Name Accession Description Interval E-value
PH_Skap1 cd13380
Src kinase-associated phosphoprotein 1 Pleckstrin homology (PH) domain; Adaptor protein Skap1 ...
108-213 7.58e-70

Src kinase-associated phosphoprotein 1 Pleckstrin homology (PH) domain; Adaptor protein Skap1 (also called Skap55/Src kinase-associated phosphoprotein of 55 kDa) and its partner, ADAP (adhesion and degranulation promoting adapter protein) help reorganize the cytoskeleton and/or promote integrin-mediated adhesion upon immunoreceptor activation. Skap1 is also involved in T Cell Receptor (TCR)-induced RapL-Rap1 complex formation and LFA-1 activation. Skap1 has an N-terminal coiled-coil conformation which is proposed to be involved in homodimer formation, a central PH domain and a C-terminal SH3 domain that associates with ADAP. The Skap1 PH domain plays a role in controlling integrin function via recruitment of ADAP-SKAP complexes to integrins as well as in controlling the ability of ADAP to interact with the CBM signalosome and regulate NF-kappaB. SKAP1 is necessary for RapL binding to membranes in a PH domain-dependent manner and the PI3K pathway. Skap adaptor proteins couple receptors to cytoskeletal rearrangements. Skap55/Skap1, Skap2, and Skap-homology (Skap-hom) have an N-terminal coiled-coil conformation, a central PH domain and a C-terminal SH3 domain. Their PH domains bind 3'-phosphoinositides as well as directly affecting targets such as in Skap55 where it directly affecting integrin regulation by ADAP and NF-kappaB activation or in Skap-hom where the dimerization and PH domains comprise a 3'-phosphoinositide-gated molecular switch that controls ruffle formation. PH domains have diverse functions, but in general are involved in targeting proteins to the appropriate cellular location or in the interaction with a binding partner. They share little sequence conservation, but all have a common fold, which is electrostatically polarized. Less than 10% of PH domains bind phosphoinositide phosphates (PIPs) with high affinity and specificity. PH domains are distinguished from other PIP-binding domains by their specific high-affinity binding to PIPs with two vicinal phosphate groups: PtdIns(3,4)P2, PtdIns(4,5)P2 or PtdIns(3,4,5)P3 which results in targeting some PH domain proteins to the plasma membrane. A few display strong specificity in lipid binding. Any specificity is usually determined by loop regions or insertions in the N-terminus of the domain, which are not conserved across all PH domains. PH domains are found in cellular signaling proteins such as serine/threonine kinase, tyrosine kinases, regulators of G-proteins, endocytotic GTPases, adaptors, as well as cytoskeletal associated molecules and in lipid associated enzymes.


:

Pssm-ID: 270180  Cd Length: 106  Bit Score: 213.56  E-value: 7.58e-70
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 115527076 108 VIKQGYLEKKSKDHSFFGSEWQKRWCVVSRGLFYYYANEKSKQPKGTFLIKGYGVRMAPHLRRDSKKESCFELTSQDRRS 187
Cdd:cd13380    1 ILKQGYLEKRSKDHSFFGSEWQKRWCVLTNRAFYYYASEKSKQPKGGFLIKGYSAQMAPHLRKDSRRDSCFELTTPGRRT 80
                         90       100
                 ....*....|....*....|....*.
gi 115527076 188 YEFTATSPAEARDWVDQISFLLKDLS 213
Cdd:cd13380   81 YQFTAASPSEARDWVDQIQFLLKDTQ 106
SH3_SKAP1 cd12044
Src Homology 3 domain of Src Kinase-Associated Phosphoprotein 1; SKAP1, also called SKAP55 ...
297-349 5.81e-33

Src Homology 3 domain of Src Kinase-Associated Phosphoprotein 1; SKAP1, also called SKAP55 (Src kinase-associated protein of 55kDa), is an immune cell-specific adaptor protein that plays an important role in T-cell adhesion, migration, and integrin clustering. It is expressed exclusively in T-lymphocytes, mast cells, and macrophages. Binding partners include ADAP (adhesion and degranulation-promoting adaptor protein), Fyn, Riam, RapL, and RasGRP. It contains a pleckstrin homology (PH) domain, a C-terminal SH3 domain, and several tyrosine phosphorylation sites. The SH3 domain of SKAP1 is necessary for its ability to regulate T-cell conjugation with antigen-presenting cells and the formation of LFA-1 clusters. SKAP1 binds primarily to a proline-rich region of ADAP through its SH3 domain; its degradation is regulated by ADAP. A secondary interaction occurs via the ADAP SH3 domain and the RKxxYxxY motif in SKAP1. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


:

Pssm-ID: 212977  Cd Length: 53  Bit Score: 116.88  E-value: 5.81e-33
                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|...
gi 115527076 297 YYQGLWDCHGDQPDELSFQRGDLIRILSKEYNMYGWWVGELNSLVGIVPKEYL 349
Cdd:cd12044    1 YYQGLWDCFGDNPDELSFQRGDLIYILSKEYNMYGWWVGELNGIVGIVPKDYL 53
 
Name Accession Description Interval E-value
PH_Skap1 cd13380
Src kinase-associated phosphoprotein 1 Pleckstrin homology (PH) domain; Adaptor protein Skap1 ...
108-213 7.58e-70

Src kinase-associated phosphoprotein 1 Pleckstrin homology (PH) domain; Adaptor protein Skap1 (also called Skap55/Src kinase-associated phosphoprotein of 55 kDa) and its partner, ADAP (adhesion and degranulation promoting adapter protein) help reorganize the cytoskeleton and/or promote integrin-mediated adhesion upon immunoreceptor activation. Skap1 is also involved in T Cell Receptor (TCR)-induced RapL-Rap1 complex formation and LFA-1 activation. Skap1 has an N-terminal coiled-coil conformation which is proposed to be involved in homodimer formation, a central PH domain and a C-terminal SH3 domain that associates with ADAP. The Skap1 PH domain plays a role in controlling integrin function via recruitment of ADAP-SKAP complexes to integrins as well as in controlling the ability of ADAP to interact with the CBM signalosome and regulate NF-kappaB. SKAP1 is necessary for RapL binding to membranes in a PH domain-dependent manner and the PI3K pathway. Skap adaptor proteins couple receptors to cytoskeletal rearrangements. Skap55/Skap1, Skap2, and Skap-homology (Skap-hom) have an N-terminal coiled-coil conformation, a central PH domain and a C-terminal SH3 domain. Their PH domains bind 3'-phosphoinositides as well as directly affecting targets such as in Skap55 where it directly affecting integrin regulation by ADAP and NF-kappaB activation or in Skap-hom where the dimerization and PH domains comprise a 3'-phosphoinositide-gated molecular switch that controls ruffle formation. PH domains have diverse functions, but in general are involved in targeting proteins to the appropriate cellular location or in the interaction with a binding partner. They share little sequence conservation, but all have a common fold, which is electrostatically polarized. Less than 10% of PH domains bind phosphoinositide phosphates (PIPs) with high affinity and specificity. PH domains are distinguished from other PIP-binding domains by their specific high-affinity binding to PIPs with two vicinal phosphate groups: PtdIns(3,4)P2, PtdIns(4,5)P2 or PtdIns(3,4,5)P3 which results in targeting some PH domain proteins to the plasma membrane. A few display strong specificity in lipid binding. Any specificity is usually determined by loop regions or insertions in the N-terminus of the domain, which are not conserved across all PH domains. PH domains are found in cellular signaling proteins such as serine/threonine kinase, tyrosine kinases, regulators of G-proteins, endocytotic GTPases, adaptors, as well as cytoskeletal associated molecules and in lipid associated enzymes.


Pssm-ID: 270180  Cd Length: 106  Bit Score: 213.56  E-value: 7.58e-70
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 115527076 108 VIKQGYLEKKSKDHSFFGSEWQKRWCVVSRGLFYYYANEKSKQPKGTFLIKGYGVRMAPHLRRDSKKESCFELTSQDRRS 187
Cdd:cd13380    1 ILKQGYLEKRSKDHSFFGSEWQKRWCVLTNRAFYYYASEKSKQPKGGFLIKGYSAQMAPHLRKDSRRDSCFELTTPGRRT 80
                         90       100
                 ....*....|....*....|....*.
gi 115527076 188 YEFTATSPAEARDWVDQISFLLKDLS 213
Cdd:cd13380   81 YQFTAASPSEARDWVDQIQFLLKDTQ 106
SH3_SKAP1 cd12044
Src Homology 3 domain of Src Kinase-Associated Phosphoprotein 1; SKAP1, also called SKAP55 ...
297-349 5.81e-33

Src Homology 3 domain of Src Kinase-Associated Phosphoprotein 1; SKAP1, also called SKAP55 (Src kinase-associated protein of 55kDa), is an immune cell-specific adaptor protein that plays an important role in T-cell adhesion, migration, and integrin clustering. It is expressed exclusively in T-lymphocytes, mast cells, and macrophages. Binding partners include ADAP (adhesion and degranulation-promoting adaptor protein), Fyn, Riam, RapL, and RasGRP. It contains a pleckstrin homology (PH) domain, a C-terminal SH3 domain, and several tyrosine phosphorylation sites. The SH3 domain of SKAP1 is necessary for its ability to regulate T-cell conjugation with antigen-presenting cells and the formation of LFA-1 clusters. SKAP1 binds primarily to a proline-rich region of ADAP through its SH3 domain; its degradation is regulated by ADAP. A secondary interaction occurs via the ADAP SH3 domain and the RKxxYxxY motif in SKAP1. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 212977  Cd Length: 53  Bit Score: 116.88  E-value: 5.81e-33
                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|...
gi 115527076 297 YYQGLWDCHGDQPDELSFQRGDLIRILSKEYNMYGWWVGELNSLVGIVPKEYL 349
Cdd:cd12044    1 YYQGLWDCFGDNPDELSFQRGDLIYILSKEYNMYGWWVGELNGIVGIVPKDYL 53
PH smart00233
Pleckstrin homology domain; Domain commonly found in eukaryotic signalling proteins. The ...
108-210 6.36e-22

Pleckstrin homology domain; Domain commonly found in eukaryotic signalling proteins. The domain family possesses multiple functions including the abilities to bind inositol phosphates, and various proteins. PH domains have been found to possess inserted domains (such as in PLC gamma, syntrophins) and to be inserted within other domains. Mutations in Brutons tyrosine kinase (Btk) within its PH domain cause X-linked agammaglobulinaemia (XLA) in patients. Point mutations cluster into the positively charged end of the molecule around the predicted binding site for phosphatidylinositol lipids.


Pssm-ID: 214574 [Multi-domain]  Cd Length: 102  Bit Score: 89.14  E-value: 6.36e-22
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 115527076   108 VIKQGYLEKKSKDhsfFGSEWQKRWCVVSRGLFYYYANEKSKQ---PKGTFLIKGYGVRMAPHlRRDSKKESCFELTSQD 184
Cdd:smart00233   1 VIKEGWLYKKSGG---GKKSWKKRYFVLFNSTLLYYKSKKDKKsykPKGSIDLSGCTVREAPD-PDSSKKPHCFEIKTSD 76
                           90       100
                   ....*....|....*....|....*.
gi 115527076   185 RRSYEFTATSPAEARDWVDQISFLLK 210
Cdd:smart00233  77 RKTLLLQAESEEEREKWVEALRKAIA 102
PH pfam00169
PH domain; PH stands for pleckstrin homology.
108-210 7.82e-16

PH domain; PH stands for pleckstrin homology.


Pssm-ID: 459697 [Multi-domain]  Cd Length: 105  Bit Score: 72.60  E-value: 7.82e-16
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 115527076  108 VIKQGYLEKKSKDhsfFGSEWQKRWCVVSRGLFYYYANE---KSKQPKGTFLIKGYGVRMAPHLrRDSKKESCFELTSQD 184
Cdd:pfam00169   1 VVKEGWLLKKGGG---KKKSWKKRYFVLFDGSLLYYKDDksgKSKEPKGSISLSGCEVVEVVAS-DSPKRKFCFELRTGE 76
                          90       100
                  ....*....|....*....|....*....
gi 115527076  185 R---RSYEFTATSPAEARDWVDQISFLLK 210
Cdd:pfam00169  77 RtgkRTYLLQAESEEERKDWIKAIQSAIR 105
SH3 smart00326
Src homology 3 domains; Src homology 3 (SH3) domains bind to target proteins through sequences ...
297-350 3.32e-12

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: 60.63  E-value: 3.32e-12
                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....*
gi 115527076   297 YYQGLWDCHGDQPDELSFQRGDLIRILSKEYNmyGWWVGELNSL-VGIVPKEYLT 350
Cdd:smart00326   4 QVRALYDYTAQDPDELSFKKGDIITVLEKSDD--GWWKGRLGRGkEGLFPSNYVE 56
SH3_2 pfam07653
Variant SH3 domain; SH3 (Src homology 3) domains are often indicative of a protein involved in ...
297-349 1.38e-07

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


Pssm-ID: 429575 [Multi-domain]  Cd Length: 54  Bit Score: 47.59  E-value: 1.38e-07
                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|...
gi 115527076  297 YYQGLWDCHGDQPDELSFQRGDLIRILSKEYNmyGWWVGELNSLVGIVPKEYL 349
Cdd:pfam07653   1 YGRVIFDYVGTDKNGLTLKKGDVVKVLGKDND--GWWEGETGGRVGLVPSTAV 51
 
Name Accession Description Interval E-value
PH_Skap1 cd13380
Src kinase-associated phosphoprotein 1 Pleckstrin homology (PH) domain; Adaptor protein Skap1 ...
108-213 7.58e-70

Src kinase-associated phosphoprotein 1 Pleckstrin homology (PH) domain; Adaptor protein Skap1 (also called Skap55/Src kinase-associated phosphoprotein of 55 kDa) and its partner, ADAP (adhesion and degranulation promoting adapter protein) help reorganize the cytoskeleton and/or promote integrin-mediated adhesion upon immunoreceptor activation. Skap1 is also involved in T Cell Receptor (TCR)-induced RapL-Rap1 complex formation and LFA-1 activation. Skap1 has an N-terminal coiled-coil conformation which is proposed to be involved in homodimer formation, a central PH domain and a C-terminal SH3 domain that associates with ADAP. The Skap1 PH domain plays a role in controlling integrin function via recruitment of ADAP-SKAP complexes to integrins as well as in controlling the ability of ADAP to interact with the CBM signalosome and regulate NF-kappaB. SKAP1 is necessary for RapL binding to membranes in a PH domain-dependent manner and the PI3K pathway. Skap adaptor proteins couple receptors to cytoskeletal rearrangements. Skap55/Skap1, Skap2, and Skap-homology (Skap-hom) have an N-terminal coiled-coil conformation, a central PH domain and a C-terminal SH3 domain. Their PH domains bind 3'-phosphoinositides as well as directly affecting targets such as in Skap55 where it directly affecting integrin regulation by ADAP and NF-kappaB activation or in Skap-hom where the dimerization and PH domains comprise a 3'-phosphoinositide-gated molecular switch that controls ruffle formation. PH domains have diverse functions, but in general are involved in targeting proteins to the appropriate cellular location or in the interaction with a binding partner. They share little sequence conservation, but all have a common fold, which is electrostatically polarized. Less than 10% of PH domains bind phosphoinositide phosphates (PIPs) with high affinity and specificity. PH domains are distinguished from other PIP-binding domains by their specific high-affinity binding to PIPs with two vicinal phosphate groups: PtdIns(3,4)P2, PtdIns(4,5)P2 or PtdIns(3,4,5)P3 which results in targeting some PH domain proteins to the plasma membrane. A few display strong specificity in lipid binding. Any specificity is usually determined by loop regions or insertions in the N-terminus of the domain, which are not conserved across all PH domains. PH domains are found in cellular signaling proteins such as serine/threonine kinase, tyrosine kinases, regulators of G-proteins, endocytotic GTPases, adaptors, as well as cytoskeletal associated molecules and in lipid associated enzymes.


Pssm-ID: 270180  Cd Length: 106  Bit Score: 213.56  E-value: 7.58e-70
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 115527076 108 VIKQGYLEKKSKDHSFFGSEWQKRWCVVSRGLFYYYANEKSKQPKGTFLIKGYGVRMAPHLRRDSKKESCFELTSQDRRS 187
Cdd:cd13380    1 ILKQGYLEKRSKDHSFFGSEWQKRWCVLTNRAFYYYASEKSKQPKGGFLIKGYSAQMAPHLRKDSRRDSCFELTTPGRRT 80
                         90       100
                 ....*....|....*....|....*.
gi 115527076 188 YEFTATSPAEARDWVDQISFLLKDLS 213
Cdd:cd13380   81 YQFTAASPSEARDWVDQIQFLLKDTQ 106
PH_Skap_family cd13266
Src kinase-associated phosphoprotein family Pleckstrin homology (PH) domain; Skap adaptor ...
108-213 5.95e-64

Src kinase-associated phosphoprotein family Pleckstrin homology (PH) domain; Skap adaptor proteins couple receptors to cytoskeletal rearrangements. Src kinase-associated phosphoprotein of 55 kDa (Skap55)/Src kinase-associated phosphoprotein 1 (Skap1), Skap2, and Skap-homology (Skap-hom) have an N-terminal coiled-coil conformation, a central PH domain and a C-terminal SH3 domain. Their PH domains bind 3'-phosphoinositides as well as directly affecting targets such as in Skap55 where it directly affecting integrin regulation by ADAP and NF-kappaB activation or in Skap-hom where the dimerization and PH domains comprise a 3'-phosphoinositide-gated molecular switch that controls ruffle formation. PH domains are only found in eukaryotes. They share little sequence conservation, but all have a common fold, which is electrostatically polarized. PH domains have diverse functions, but in general are involved in targeting proteins to the appropriate cellular location or in the interaction with a binding partner. They share little sequence conservation, but all have a common fold, which is electrostatically polarized. Less than 10% of PH domains bind phosphoinositide phosphates (PIPs) with high affinity and specificity. PH domains are distinguished from other PIP-binding domains by their specific high-affinity binding to PIPs with two vicinal phosphate groups: PtdIns(3,4)P2, PtdIns(4,5)P2 or PtdIns(3,4,5)P3 which results in targeting some PH domain proteins to the plasma membrane. A few display strong specificity in lipid binding. Any specificity is usually determined by loop regions or insertions in the N-terminus of the domain, which are not conserved across all PH domains. PH domains are found in cellular signaling proteins such as serine/threonine kinase, tyrosine kinases, regulators of G-proteins, endocytotic GTPases, adaptors, as well as cytoskeletal associated molecules and in lipid associated enzymes.


Pssm-ID: 270086  Cd Length: 106  Bit Score: 198.52  E-value: 5.95e-64
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 115527076 108 VIKQGYLEKKSKDHSFFGSEWQKRWCVVSRGLFYYYANEKSKQPKGTFLIKGYGVRMAPHLRRDSKKESCFELTSQDRRS 187
Cdd:cd13266    1 VIKAGYLEKRRKDHSFFGSEWQKRWCAISKNVFYYYGSDKDKQQKGEFAINGYDVRMNPTLRKDGKKDCCFELVCPDKRT 80
                         90       100
                 ....*....|....*....|....*.
gi 115527076 188 YEFTATSPAEARDWVDQISFLLKDLS 213
Cdd:cd13266   81 YQFTAASPEDAEDWVDQISFILQDLS 106
PH_Skap-hom_Skap2 cd13381
Src kinase-associated phosphoprotein homolog and Skap 2 Pleckstrin homology (PH) domain; ...
108-212 3.41e-49

Src kinase-associated phosphoprotein homolog and Skap 2 Pleckstrin homology (PH) domain; Adaptor protein Skap-hom, a homolog of Skap55, which interacts with actin and with ADAP (adhesion and degranulation promoting adapter protein) undergoes tyrosine phosphorylation in response to plating of bone marrow-derived macrophages on fibronectin. Skap-hom has an N-terminal coiled-coil conformation that is involved in homodimer formation, a central PH domain and a C-terminal SH3 domain that associates with ADAP. The Skap-hom PH domain regulates intracellular targeting; its interaction with the DM domain inhibits Skap-hom actin-based ruffles in macrophages and its binding to 3'-phosphoinositides reverses this autoinhibition. The Skap-hom PH domain binds PI[3,4]P2 and PI[3,4,5]P3, but not to PI[3]P, PI[5]P, or PI[4,5]P2. Skap2 is a downstream target of Heat shock transcription factor 4 (HSF4) and functions in the regulation of actin reorganization during lens differentiation. It is thought that SKAP2 anchors the complex of tyrosine kinase adaptor protein 2 (NCK20/focal adhesion to fibroblast growth factor receptors at the lamellipodium in lens epithelial cells. Skap2 has an N-terminal coiled-coil conformation which interacts with the SH2 domain of NCK2, a central PH domain and a C-terminal SH3 domain that associates with ADAP (adhesion and degranulation promoting adapter protein)/FYB (the Fyn binding protein). Skap2 PH domain binds to membrane lipids. Skap adaptor proteins couple receptors to cytoskeletal rearrangements. Src kinase-associated phosphoprotein of 55 kDa (Skap55)/Src kinase-associated phosphoprotein 1 (Skap1), Skap2, and Skap-hom have an N-terminal coiled-coil conformation, a central PH domain and a C-terminal SH3 domain. Their PH domains bind 3'-phosphoinositides as well as directly affecting targets such as in Skap55 where it directly affecting integrin regulation by ADAP and NF-kappaB activation or in Skap-hom where the dimerization and PH domains comprise a 3'-phosphoinositide-gated molecular switch that controls ruffle formation. PH domains have diverse functions, but in general are involved in targeting proteins to the appropriate cellular location or in the interaction with a binding partner. They share little sequence conservation, but all have a common fold, which is electrostatically polarized. Less than 10% of PH domains bind phosphoinositide phosphates (PIPs) with high affinity and specificity. PH domains are distinguished from other PIP-binding domains by their specific high-affinity binding to PIPs with two vicinal phosphate groups: PtdIns(3,4)P2, PtdIns(4,5)P2 or PtdIns(3,4,5)P3 which results in targeting some PH domain proteins to the plasma membrane. A few display strong specificity in lipid binding. Any specificity is usually determined by loop regions or insertions in the N-terminus of the domain, which are not conserved across all PH domains. PH domains are found in cellular signaling proteins such as serine/threonine kinase, tyrosine kinases, regulators of G-proteins, endocytotic GTPases, adaptors, as well as cytoskeletal associated molecules and in lipid associated enzymes.


Pssm-ID: 270181  Cd Length: 106  Bit Score: 160.89  E-value: 3.41e-49
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 115527076 108 VIKQGYLEKKSKDHSFFGSEWQKRWCVVSRGLFYYYANEKSKQPKGTFLIKGYGVRMAPHLRRDSKKESCFELTSQDRRS 187
Cdd:cd13381    1 VLKAGYLEKRRKDHSFFGFEWQKRWCALSNSVFYYYGSDKDKQQKGEFAIDGYDVKMNNTLRKDAKKDCCFEICAPDKRV 80
                         90       100
                 ....*....|....*....|....*
gi 115527076 188 YEFTATSPAEARDWVDQISFLLKDL 212
Cdd:cd13381   81 YQFTAASPKEAEEWVQQIKFILQDL 105
SH3_SKAP1 cd12044
Src Homology 3 domain of Src Kinase-Associated Phosphoprotein 1; SKAP1, also called SKAP55 ...
297-349 5.81e-33

Src Homology 3 domain of Src Kinase-Associated Phosphoprotein 1; SKAP1, also called SKAP55 (Src kinase-associated protein of 55kDa), is an immune cell-specific adaptor protein that plays an important role in T-cell adhesion, migration, and integrin clustering. It is expressed exclusively in T-lymphocytes, mast cells, and macrophages. Binding partners include ADAP (adhesion and degranulation-promoting adaptor protein), Fyn, Riam, RapL, and RasGRP. It contains a pleckstrin homology (PH) domain, a C-terminal SH3 domain, and several tyrosine phosphorylation sites. The SH3 domain of SKAP1 is necessary for its ability to regulate T-cell conjugation with antigen-presenting cells and the formation of LFA-1 clusters. SKAP1 binds primarily to a proline-rich region of ADAP through its SH3 domain; its degradation is regulated by ADAP. A secondary interaction occurs via the ADAP SH3 domain and the RKxxYxxY motif in SKAP1. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 212977  Cd Length: 53  Bit Score: 116.88  E-value: 5.81e-33
                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|...
gi 115527076 297 YYQGLWDCHGDQPDELSFQRGDLIRILSKEYNMYGWWVGELNSLVGIVPKEYL 349
Cdd:cd12044    1 YYQGLWDCFGDNPDELSFQRGDLIYILSKEYNMYGWWVGELNGIVGIVPKDYL 53
SH3_SKAP2 cd12045
Src Homology 3 domain of Src Kinase-Associated Phosphoprotein 2; SKAP2, also called ...
297-349 8.99e-28

Src Homology 3 domain of Src Kinase-Associated Phosphoprotein 2; SKAP2, also called SKAP55-Related (SKAP55R) or SKAP55 homolog (SKAP-HOM or SKAP55-HOM), is an immune cell-specific adaptor protein that plays an important role in adhesion and migration of B-cells and macrophages. Binding partners include ADAP (adhesion and degranulation-promoting adaptor protein), YopH, SHPS1, and HPK1. SKAP2 has also been identified as a substrate for lymphoid-specific tyrosine phosphatase (Lyp), which has been implicated in a wide variety of autoimmune diseases. It contains a pleckstrin homology (PH) domain, a C-terminal SH3 domain, and several tyrosine phosphorylation sites. Like SKAP1, SKAP2 is expected to bind primarily to a proline-rich region of ADAP through its SH3 domain; its degradation may be regulated by ADAP. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 212978  Cd Length: 53  Bit Score: 103.06  E-value: 8.99e-28
                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|...
gi 115527076 297 YYQGLWDCHGDQPDELSFQRGDLIRILSKEYNMYGWWVGELNSLVGIVPKEYL 349
Cdd:cd12045    1 FYQGLWDCTGDQPDELSFKRGDTIYILSKEYNRFGWWVGEMKGTIGLVPKAYI 53
SH3_SKAP1-like cd11866
Src Homology 3 domain of Src Kinase-Associated Phosphoprotein 1 and similar proteins; This ...
297-349 1.64e-26

Src Homology 3 domain of Src Kinase-Associated Phosphoprotein 1 and similar proteins; This subfamily is composed of SKAP1, SKAP2, and similar proteins. SKAP1 and SKAP2 are immune cell-specific adaptor proteins that play roles in T- and B-cell adhesion, respectively, and are thus important in the migration of T- and B-cells to sites of inflammation and for movement during T-cell conjugation with antigen-presenting cells. Both SKAP1 and SKAP2 bind to ADAP (adhesion and degranulation-promoting adaptor protein), among many other binding partners. They contain a pleckstrin homology (PH) domain, a C-terminal SH3 domain, and several tyrosine phosphorylation sites. The SH3 domain of SKAP1 is necessary for its ability to regulate T-cell conjugation with antigen-presenting cells and the formation of LFA-1 clusters. SKAP1 binds primarily to a proline-rich region of ADAP through its SH3 domain; its degradation is regulated by ADAP. A secondary interaction occurs via the ADAP SH3 domain and the RKxxYxxY motif in SKAP1. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 212800  Cd Length: 53  Bit Score: 99.81  E-value: 1.64e-26
                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|...
gi 115527076 297 YYQGLWDCHGDQPDELSFQRGDLIRILSKEYNMYGWWVGELNSLVGIVPKEYL 349
Cdd:cd11866    1 WYMGLWDCSGNEPDELSFKRGDLIYIISKEYDSFGWWVGELNGKVGLVPKDYL 53
PH smart00233
Pleckstrin homology domain; Domain commonly found in eukaryotic signalling proteins. The ...
108-210 6.36e-22

Pleckstrin homology domain; Domain commonly found in eukaryotic signalling proteins. The domain family possesses multiple functions including the abilities to bind inositol phosphates, and various proteins. PH domains have been found to possess inserted domains (such as in PLC gamma, syntrophins) and to be inserted within other domains. Mutations in Brutons tyrosine kinase (Btk) within its PH domain cause X-linked agammaglobulinaemia (XLA) in patients. Point mutations cluster into the positively charged end of the molecule around the predicted binding site for phosphatidylinositol lipids.


Pssm-ID: 214574 [Multi-domain]  Cd Length: 102  Bit Score: 89.14  E-value: 6.36e-22
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 115527076   108 VIKQGYLEKKSKDhsfFGSEWQKRWCVVSRGLFYYYANEKSKQ---PKGTFLIKGYGVRMAPHlRRDSKKESCFELTSQD 184
Cdd:smart00233   1 VIKEGWLYKKSGG---GKKSWKKRYFVLFNSTLLYYKSKKDKKsykPKGSIDLSGCTVREAPD-PDSSKKPHCFEIKTSD 76
                           90       100
                   ....*....|....*....|....*.
gi 115527076   185 RRSYEFTATSPAEARDWVDQISFLLK 210
Cdd:smart00233  77 RKTLLLQAESEEEREKWVEALRKAIA 102
PH_3BP2 cd13308
SH3 domain-binding protein 2 Pleckstrin homology (PH) domain; SH3BP2 (the gene that encodes ...
108-205 4.24e-16

SH3 domain-binding protein 2 Pleckstrin homology (PH) domain; SH3BP2 (the gene that encodes the adaptor protein 3BP2), HD, ITU, IT10C3, and ADD1 are located near the Huntington's Disease Gene on Human Chromosome 4pl6.3. SH3BP2 lies in a region that is often missing in individuals with Wolf-Hirschhorn syndrome (WHS). Gain of function mutations in SH3BP2 causes enhanced B-cell antigen receptor (BCR)-mediated activation of nuclear factor of activated T cells (NFAT), resulting in a rare, genetic disorder called cherubism. This results in an increase in the signaling complex formation with Syk, phospholipase C-gamma2 (PLC-gamma2), and Vav1. It was recently discovered that Tankyrase regulates 3BP2 stability through ADP-ribosylation and ubiquitylation by the E3-ubiquitin ligase. Cherubism mutations uncouple 3BP2 from Tankyrase-mediated protein destruction, which results in its stabilization and subsequent hyperactivation of the Src, Syk, and Vav signaling pathways. SH3BP2 is also a potential negative regulator of the abl oncogene. PH domains have diverse functions, but in general are involved in targeting proteins to the appropriate cellular location or in the interaction with a binding partner. They share little sequence conservation, but all have a common fold, which is electrostatically polarized. Less than 10% of PH domains bind phosphoinositide phosphates (PIPs) with high affinity and specificity. PH domains are distinguished from other PIP-binding domains by their specific high-affinity binding to PIPs with two vicinal phosphate groups: PtdIns(3,4)P2, PtdIns(4,5)P2 or PtdIns(3,4,5)P3 which results in targeting some PH domain proteins to the plasma membrane. A few display strong specificity in lipid binding. Any specificity is usually determined by loop regions or insertions in the N-terminus of the domain, which are not conserved across all PH domains. PH domains are found in cellular signaling proteins such as serine/threonine kinase, tyrosine kinases, regulators of G-proteins, endocytotic GTPases, adaptors, as well as cytoskeletal associated molecules and in lipid associated enzymes.


Pssm-ID: 270118  Cd Length: 113  Bit Score: 73.59  E-value: 4.24e-16
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 115527076 108 VIKQGYLEKKSKDHsFFGSEWQKRWCVVSRGLFYYYANEKSKQPKGTFLIKGYGVRMAPHLRrdSKKESCFEL--TSQDR 185
Cdd:cd13308    9 VIHSGTLTKKGGSQ-KTLQNWQLRYVIIHQGCVYYYKNDQSAKPKGVFSLNGYNRRAAEERT--SKLKFVFKIihLSPDH 85
                         90       100
                 ....*....|....*....|
gi 115527076 186 RSYEFTATSPAEARDWVDQI 205
Cdd:cd13308   86 RTWYFAAKSEDEMSEWMEYI 105
PH pfam00169
PH domain; PH stands for pleckstrin homology.
108-210 7.82e-16

PH domain; PH stands for pleckstrin homology.


Pssm-ID: 459697 [Multi-domain]  Cd Length: 105  Bit Score: 72.60  E-value: 7.82e-16
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 115527076  108 VIKQGYLEKKSKDhsfFGSEWQKRWCVVSRGLFYYYANE---KSKQPKGTFLIKGYGVRMAPHLrRDSKKESCFELTSQD 184
Cdd:pfam00169   1 VVKEGWLLKKGGG---KKKSWKKRYFVLFDGSLLYYKDDksgKSKEPKGSISLSGCEVVEVVAS-DSPKRKFCFELRTGE 76
                          90       100
                  ....*....|....*....|....*....
gi 115527076  185 R---RSYEFTATSPAEARDWVDQISFLLK 210
Cdd:pfam00169  77 RtgkRTYLLQAESEEERKDWIKAIQSAIR 105
PH cd00821
Pleckstrin homology (PH) domain; PH domains have diverse functions, but in general are ...
110-205 2.60e-15

Pleckstrin homology (PH) domain; PH domains have diverse functions, but in general are involved in targeting proteins to the appropriate cellular location or in the interaction with a binding partner. They share little sequence conservation, but all have a common fold, which is electrostatically polarized. Less than 10% of PH domains bind phosphoinositide phosphates (PIPs) with high affinity and specificity. PH domains are distinguished from other PIP-binding domains by their specific high-affinity binding to PIPs with two vicinal phosphate groups: PtdIns(3,4)P2, PtdIns(4,5)P2 or PtdIns(3,4,5)P3 which results in targeting some PH domain proteins to the plasma membrane. A few display strong specificity in lipid binding. Any specificity is usually determined by loop regions or insertions in the N-terminus of the domain, which are not conserved across all PH domains. PH domains are found in cellular signaling proteins such as serine/threonine kinase, tyrosine kinases, regulators of G-proteins, endocytotic GTPases, adaptors, as well as cytoskeletal associated molecules and in lipid associated enzymes.


Pssm-ID: 275388 [Multi-domain]  Cd Length: 92  Bit Score: 70.65  E-value: 2.60e-15
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 115527076 110 KQGYLEKKSKDHSFfgsEWQKRWCVVSRGLFYYYANEK--SKQPKGTF-LIKGYGVRMAPhlrrDSKKESCFELTSQDRR 186
Cdd:cd00821    1 KEGYLLKRGGGGLK---SWKKRWFVLFEGVLLYYKSKKdsSYKPKGSIpLSGILEVEEVS----PKERPHCFELVTPDGR 73
                         90
                 ....*....|....*....
gi 115527076 187 SYEFTATSPAEARDWVDQI 205
Cdd:cd00821   74 TYYLQADSEEERQEWLKAL 92
PH_PEPP1_2_3 cd13248
Phosphoinositol 3-phosphate binding proteins 1, 2, and 3 pleckstrin homology (PH) domain; ...
105-206 6.87e-13

Phosphoinositol 3-phosphate binding proteins 1, 2, and 3 pleckstrin homology (PH) domain; PEPP1 (also called PLEKHA4/PH domain-containing family A member 4 and RHOXF1/Rhox homeobox family member 1), and related homologs PEPP2 (also called PLEKHA5/PH domain-containing family A member 5) and PEPP3 (also called PLEKHA6/PH domain-containing family A member 6), have PH domains that interact specifically with PtdIns(3,4)P3. Other proteins that bind PtdIns(3,4)P3 specifically are: TAPP1 (tandem PH-domain-containing protein-1) and TAPP2], PtdIns3P AtPH1, and Ptd- Ins(3,5)P2 (centaurin-beta2). All of these proteins contain at least 5 of the 6 conserved amino acids that make up the putative phosphatidylinositol 3,4,5- trisphosphate-binding motif (PPBM) located at their N-terminus. PH domains have diverse functions, but in general are involved in targeting proteins to the appropriate cellular location or in the interaction with a binding partner. They share little sequence conservation, but all have a common fold, which is electrostatically polarized. Less than 10% of PH domains bind phosphoinositide phosphates (PIPs) with high affinity and specificity. PH domains are distinguished from other PIP-binding domains by their specific high-affinity binding to PIPs with two vicinal phosphate groups: PtdIns(3,4)P2, PtdIns(4,5)P2 or PtdIns(3,4,5)P3 which results in targeting some PH domain proteins to the plasma membrane. A few display strong specificity in lipid binding. Any specificity is usually determined by loop regions or insertions in the N-terminus of the domain, which are not conserved across all PH domains. PH domains are found in cellular signaling proteins such as serine/threonine kinase, tyrosine kinases, regulators of G-proteins, endocytotic GTPases, adaptors, as well as cytoskeletal associated molecules and in lipid associated enzymes.


Pssm-ID: 270068  Cd Length: 104  Bit Score: 64.22  E-value: 6.87e-13
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 115527076 105 LDNVIKQGYLEKKSkdhsffGS---EWQKRWCVVSRGLFYYYANEKSKQPKGTFLIKGYGVRMAPHLRRDSKKEScFELT 181
Cdd:cd13248    4 NAPVVMSGWLHKQG------GSglkNWRKRWFVLKDNCLYYYKDPEEEKALGSILLPSYTISPAPPSDEISRKFA-FKAE 76
                         90       100
                 ....*....|....*....|....*
gi 115527076 182 SQDRRSYEFTATSPAEARDWVDQIS 206
Cdd:cd13248   77 HANMRTYYFAADTAEEMEQWMNAMS 101
SH3 smart00326
Src homology 3 domains; Src homology 3 (SH3) domains bind to target proteins through sequences ...
297-350 3.32e-12

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: 60.63  E-value: 3.32e-12
                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....*
gi 115527076   297 YYQGLWDCHGDQPDELSFQRGDLIRILSKEYNmyGWWVGELNSL-VGIVPKEYLT 350
Cdd:smart00326   4 QVRALYDYTAQDPDELSFKKGDIITVLEKSDD--GWWKGRLGRGkEGLFPSNYVE 56
PH_RasGRF1_2 cd13261
Ras-specific guanine nucleotide-releasing factors 1 and 2 Pleckstrin homology (PH) domain; ...
110-206 8.67e-12

Ras-specific guanine nucleotide-releasing factors 1 and 2 Pleckstrin homology (PH) domain; RasGRF1 (also called GRF1; CDC25Mm/Ras-specific nucleotide exchange factor CDC25; GNRP/Guanine nucleotide-releasing protein) and RasGRF2 (also called GRF2; Ras guanine nucleotide exchange factor 2) are a family of guanine nucleotide exchange factors (GEFs). They both promote the exchange of Ras-bound GDP by GTP, thereby regulating the RAS signaling pathway. RasGRF1 and RasGRF2 form homooligomers and heterooligomers. GRF1 has 3 isoforms and GRF2 has 2 isoforms. The longest isoforms of RasGRF1 and RasGRF2 contain the following domains: a Rho-GEF domain sandwiched between 2 PH domains, IQ domains, a REM (Ras exchanger motif) domain, and a Ras-GEF domainwhich gives them the capacity to activate both Ras and Rac GTPases in response to signals from a variety of neurotransmitter receptors. Their IQ domains allow them to act as calcium sensors to mediate the actions of NMDA-type and calcium-permeable AMPA-type glutamate receptors. GRF1 also mediates the action of dopamine receptors that signal through cAMP. GRF1 and GRF2 play strikingly different roles in regulating MAP kinase family members, neuronal synaptic plasticity, specific forms of learning and memory, and behavioral responses to psychoactive drugs. PH domains have diverse functions, but in general are involved in targeting proteins to the appropriate cellular location or in the interaction with a binding partner. They share little sequence conservation, but all have a common fold, which is electrostatically polarized. Less than 10% of PH domains bind phosphoinositide phosphates (PIPs) with high affinity and specificity. PH domains are distinguished from other PIP-binding domains by their specific high-affinity binding to PIPs with two vicinal phosphate groups: PtdIns(3,4)P2, PtdIns(4,5)P2 or PtdIns(3,4,5)P3 which results in targeting some PH domain proteins to the plasma membrane. A few display strong specificity in lipid binding. Any specificity is usually determined by loop regions or insertions in the N-terminus of the domain, which are not conserved across all PH domains. PH domains are found in cellular signaling proteins such as serine/threonine kinase, tyrosine kinases, regulators of G-proteins, endocytotic GTPases, adaptors, as well as cytoskeletal associated molecules and in lipid associated enzymes.


Pssm-ID: 270081  Cd Length: 136  Bit Score: 62.06  E-value: 8.67e-12
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 115527076 110 KQGYLEKKSKDhsffGSEWQKRWCVVSRGLFYYYANEKSKQPKGTFLIKGYGVRMAPHLRRDSK------KESCFELT-- 181
Cdd:cd13261    7 KRGYLSKKTSD----SGKWHERWFALYQNLLFYFENESSSRPSGLYLLEGCYCERLPTPKGALKgkdhleKQHYFTISfr 82
                         90       100
                 ....*....|....*....|....*
gi 115527076 182 SQDRRSYEFTATSPAEARDWVDQIS 206
Cdd:cd13261   83 HENQRQYELRAETESDCDEWVEAIK 107
SH3 cd00174
Src Homology 3 domain superfamily; Src Homology 3 (SH3) domains are protein interaction ...
297-348 1.57e-10

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: 55.93  E-value: 1.57e-10
                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|...
gi 115527076 297 YYQGLWDCHGDQPDELSFQRGDLIRILSKEYNmyGWWVGELNSL-VGIVPKEY 348
Cdd:cd00174    1 YARALYDYEAQDDDELSFKKGDIITVLEKDDD--GWWEGELNGGrEGLFPANY 51
PH_RhoGap25-like cd13263
Rho GTPase activating protein 25 and related proteins Pleckstrin homology (PH) domain; ...
107-205 6.72e-10

Rho GTPase activating protein 25 and related proteins Pleckstrin homology (PH) domain; RhoGAP25 (also called ArhGap25) like other RhoGaps are involved in cell polarity, cell morphology and cytoskeletal organization. They act as GTPase activators for the Rac-type GTPases by converting them to an inactive GDP-bound state and control actin remodeling by inactivating Rac downstream of Rho leading to suppress leading edge protrusion and promotes cell retraction to achieve cellular polarity and are able to suppress RAC1 and CDC42 activity in vitro. Overexpression of these proteins induces cell rounding with partial or complete disruption of actin stress fibers and formation of membrane ruffles, lamellipodia, and filopodia. This hierarchy contains RhoGAP22, RhoGAP24, and RhoGAP25. Members here contain an N-terminal PH domain followed by a RhoGAP domain and either a BAR or TATA Binding Protein (TBP) Associated Factor 4 (TAF4) domain. PH domains have diverse functions, but in general are involved in targeting proteins to the appropriate cellular location or in the interaction with a binding partner. They share little sequence conservation, but all have a common fold, which is electrostatically polarized. Less than 10% of PH domains bind phosphoinositide phosphates (PIPs) with high affinity and specificity. PH domains are distinguished from other PIP-binding domains by their specific high-affinity binding to PIPs with two vicinal phosphate groups: PtdIns(3,4)P2, PtdIns(4,5)P2 or PtdIns(3,4,5)P3 which results in targeting some PH domain proteins to the plasma membrane. A few display strong specificity in lipid binding. Any specificity is usually determined by loop regions or insertions in the N-terminus of the domain, which are not conserved across all PH domains. PH domains are found in cellular signaling proteins such as serine/threonine kinase, tyrosine kinases, regulators of G-proteins, endocytotic GTPases, adaptors, as well as cytoskeletal associated molecules and in lipid associated enzymes.


Pssm-ID: 270083  Cd Length: 114  Bit Score: 55.85  E-value: 6.72e-10
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 115527076 107 NVIKQGYLEKKSkdhSFFGSeWQKRWCVVSRGLFYYYANEKSKQPKGTFLIKGYGVRMAPHLRRDSKKeSCFELT---SQ 183
Cdd:cd13263    2 RPIKSGWLKKQG---SIVKN-WQQRWFVLRGDQLYYYKDEDDTKPQGTIPLPGNKVKEVPFNPEEPGK-FLFEIIpggGG 76
                         90       100
                 ....*....|....*....|....*..
gi 115527076 184 DRR-----SYEFTATSPAEARDWVDQI 205
Cdd:cd13263   77 DRMtsnhdSYLLMANSQAEMEEWVKVI 103
PH_GRP1-like cd01252
General Receptor for Phosphoinositides-1-like Pleckstrin homology (PH) domain; GRP1/cytohesin3 ...
107-206 7.84e-10

General Receptor for Phosphoinositides-1-like Pleckstrin homology (PH) domain; GRP1/cytohesin3 and the related proteins ARNO (ARF nucleotide-binding site opener)/cytohesin-2 and cytohesin-1 are ARF exchange factors that contain a pleckstrin homology (PH) domain thought to target these proteins to cell membranes through binding polyphosphoinositides. The PH domains of all three proteins exhibit relatively high affinity for PtdIns(3,4,5)P3. Within the Grp1 family, diglycine (2G) and triglycine (3G) splice variants, differing only in the number of glycine residues in the PH domain, strongly influence the affinity and specificity for phosphoinositides. The 2G variants selectively bind PtdIns(3,4,5)P3 with high affinity,the 3G variants bind PtdIns(3,4,5)P3 with about 30-fold lower affinity and require the polybasic region for plasma membrane targeting. These ARF-GEFs share a common, tripartite structure consisting of an N-terminal coiled-coil domain, a central domain with homology to the yeast protein Sec7, a PH domain, and a C-terminal polybasic region. The Sec7 domain is autoinhibited by conserved elements proximal to the PH domain. GRP1 binds to the DNA binding domain of certain nuclear receptors (TRalpha, TRbeta, AR, ER, but not RXR), and can repress thyroid hormone receptor (TR)-mediated transactivation by decreasing TR-complex formation on thyroid hormone response elements. ARNO promotes sequential activation of Arf6, Cdc42 and Rac1 and insulin secretion. Cytohesin acts as a PI 3-kinase effector mediating biological responses including cell spreading and adhesion, chemotaxis, protein trafficking, and cytoskeletal rearrangements, only some of which appear to depend on their ability to activate ARFs. PH domains have diverse functions, but in general are involved in targeting proteins to the appropriate cellular location or in the interaction with a binding partner. They share little sequence conservation, but all have a common fold, which is electrostatically polarized. Less than 10% of PH domains bind phosphoinositide phosphates (PIPs) with high affinity and specificity. PH domains are distinguished from other PIP-binding domains by their specific high-affinity binding to PIPs with two vicinal phosphate groups: PtdIns(3,4)P2, PtdIns(4,5)P2 or PtdIns(3,4,5)P3 which results in targeting some PH domain proteins to the plasma membrane. A few display strong specificity in lipid binding. Any specificity is usually determined by loop regions or insertions in the N-terminus of the domain, which are not conserved across all PH domains. PH domains are found in cellular signaling proteins such as serine/threonine kinase, tyrosine kinases, regulators of G-proteins, endocytotic GTPases, adaptors, as well as cytoskeletal associated molecules and in lipid associated enzymes.


Pssm-ID: 269954  Cd Length: 119  Bit Score: 56.17  E-value: 7.84e-10
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 115527076 107 NVIKQGYLEKKSKDHSffgsEWQKRWCVVSRGLFYYYANEKSKQPKGTFLIKGYGVRMAPhlrrDSKKESCFEL------ 180
Cdd:cd01252    2 NPDREGWLLKLGGRVK----SWKRRWFILTDNCLYYFEYTTDKEPRGIIPLENLSVREVE----DKKKPFCFELyspsng 73
                         90       100       110       120
                 ....*....|....*....|....*....|....*....|
gi 115527076 181 -------TSQDRR-------SYEFTATSPAEARDWVDQIS 206
Cdd:cd01252   74 qvikackTDSDGKvvegnhtVYRISAASEEERDEWIKSIK 113
PH_CNK_mammalian-like cd01260
Connector enhancer of KSR (Kinase suppressor of ras) (CNK) pleckstrin homology (PH) domain; ...
103-205 1.56e-09

Connector enhancer of KSR (Kinase suppressor of ras) (CNK) pleckstrin homology (PH) domain; CNK family members function as protein scaffolds, regulating the activity and the subcellular localization of RAS activated RAF. There is a single CNK protein present in Drosophila and Caenorhabditis elegans in contrast to mammals which have 3 CNK proteins (CNK1, CNK2, and CNK3). All of the CNK members contain a sterile a motif (SAM), a conserved region in CNK (CRIC) domain, and a PSD-95/DLG-1/ZO-1 (PDZ) domain, and, with the exception of CNK3, a PH domain. A CNK2 splice variant CNK2A also has a PDZ domain-binding motif at its C terminus and Drosophila CNK (D-CNK) also has a domain known as the Raf-interacting region (RIR) that mediates binding of the Drosophila Raf kinase. This cd contains CNKs from mammals, chickens, amphibians, fish, and crustacea. PH domains have diverse functions, but in general are involved in targeting proteins to the appropriate cellular location or in the interaction with a binding partner. They share little sequence conservation, but all have a common fold, which is electrostatically polarized. Less than 10% of PH domains bind phosphoinositide phosphates (PIPs) with high affinity and specificity. PH domains are distinguished from other PIP-binding domains by their specific high-affinity binding to PIPs with two vicinal phosphate groups: PtdIns(3,4)P2, PtdIns(4,5)P2 or PtdIns(3,4,5)P3 which results in targeting some PH domain proteins to the plasma membrane. A few display strong specificity in lipid binding. Any specificity is usually determined by loop regions or insertions in the N-terminus of the domain, which are not conserved across all PH domains. PH domains are found in cellular signaling proteins such as serine/threonine kinase, tyrosine kinases, regulators of G-proteins, endocytotic GTPases, adaptors, as well as cytoskeletal associated molecules and in lipid associated enzymes.


Pssm-ID: 269962  Cd Length: 114  Bit Score: 55.11  E-value: 1.56e-09
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 115527076 103 QELDNVIKQGYLEKKSKDHSFFGSEWQKRWCVVSRGLFYYYANEKSKQPKGTFLIKGYGVRMAphlrRDSKKESCFELTS 182
Cdd:cd01260    8 KDLGRGDCQGWLWKKKEAKSFFGQKWKKYWFVLKGSSLYWYSNQQDEKAEGFINLPDFKIERA----SECKKKYAFKACH 83
                         90       100
                 ....*....|....*....|...
gi 115527076 183 QDRRSYEFTATSPAEARDWVDQI 205
Cdd:cd01260   84 PKIKTFYFAAENLDDMNKWLSKL 106
PH_Ses cd13288
Sesquipedalian family Pleckstrin homology (PH) domain; The sesquipedalian family has 2 ...
110-206 2.47e-09

Sesquipedalian family Pleckstrin homology (PH) domain; The sesquipedalian family has 2 mammalian members: Ses1 and Ses2, which are also callled 7 kDa inositol polyphosphate phosphatase-interacting protein 1 and 2. They play a role in endocytic trafficking and are required for receptor recycling from endosomes, both to the trans-Golgi network and the plasma membrane. Members of this family form homodimers and heterodimers. Sesquipedalian interacts with inositol polyphosphate 5-phosphatase OCRL-1 (INPP5F) also known as Lowe oculocerebrorenal syndrome protein, a phosphatase enzyme that is involved in actin polymerization and is found in the trans-Golgi network and INPP5B. Sesquipedalian contains a single PH domain. PH domains have diverse functions, but in general are involved in targeting proteins to the appropriate cellular location or in the interaction with a binding partner. They share little sequence conservation, but all have a common fold, which is electrostatically polarized. Less than 10% of PH domains bind phosphoinositide phosphates (PIPs) with high affinity and specificity. PH domains are distinguished from other PIP-binding domains by their specific high-affinity binding to PIPs with two vicinal phosphate groups: PtdIns(3,4)P2, PtdIns(4,5)P2 or PtdIns(3,4,5)P3 which results in targeting some PH domain proteins to the plasma membrane. A few display strong specificity in lipid binding. Any specificity is usually determined by loop regions or insertions in the N-terminus of the domain, which are not conserved across all PH domains. PH domains are found in cellular signaling proteins such as serine/threonine kinase, tyrosine kinases, regulators of G-proteins, endocytotic GTPases, adaptors, as well as cytoskeletal associated molecules and in lipid associated enzymes.


Pssm-ID: 270105 [Multi-domain]  Cd Length: 120  Bit Score: 54.55  E-value: 2.47e-09
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 115527076 110 KQGYLEKKSKDHSFFgsewQKRWCVVSRGLFYYYANEKSKQPKGTFLIKGYGVRMAphlrrDSKKESCFELT--SQDRRS 187
Cdd:cd13288   10 KEGYLWKKGERNTSY----QKRWFVLKGNLLFYFEKKGDREPLGVIVLEGCTVELA-----EDAEPYAFAIRfdGPGARS 80
                         90
                 ....*....|....*....
gi 115527076 188 YEFTATSPAEARDWVDQIS 206
Cdd:cd13288   81 YVLAAENQEDMESWMKALS 99
SH3_D21-like cd12142
Src Homology 3 domain of SH3 domain-containing protein 21 (SH3D21) and similar proteins; ...
297-349 4.22e-09

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


Pssm-ID: 213018 [Multi-domain]  Cd Length: 55  Bit Score: 52.08  E-value: 4.22e-09
                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|...
gi 115527076 297 YYQGLWDCHGDQPDELSFQRGDLIRILSKEYNMYGWWVGELNSLVGIVPKEYL 349
Cdd:cd12142    1 YCRVLFDYNPVAPDELALKKGDVIEVISKETEDEGWWEGELNGRRGFFPDNFV 53
SH3_Ysc84p_like cd11842
Src homology 3 domain of Ysc84p and similar fungal proteins; This family is composed of the ...
301-349 4.66e-09

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


Pssm-ID: 212776 [Multi-domain]  Cd Length: 55  Bit Score: 52.04  E-value: 4.66e-09
                         10        20        30        40
                 ....*....|....*....|....*....|....*....|....*....
gi 115527076 301 LWDCHGDQPDELSFQRGDLIRILSKEYNMYGWWVGELNSLVGIVPKEYL 349
Cdd:cd11842    5 LYDFAGEQPGDLAFQKGDIITILKKSDSQNDWWTGRIGGREGIFPANYV 53
SH3_CD2AP-like_3 cd11875
Third Src Homology 3 domain (SH3C) of CD2-associated protein and similar proteins; This ...
297-345 5.73e-09

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


Pssm-ID: 212808 [Multi-domain]  Cd Length: 55  Bit Score: 51.58  E-value: 5.73e-09
                         10        20        30        40
                 ....*....|....*....|....*....|....*....|....*....
gi 115527076 297 YYQGLWDCHGDQPDELSFQRGDLIRILSKEYNMYGWWVGELNSLVGIVP 345
Cdd:cd11875    1 KARVLFDYEAENEDELTLREGDIVTILSKDCEDKGWWKGELNGKRGVFP 49
SH3_SH3YL1_like cd11841
Src homology 3 domain of SH3 domain containing Ysc84-like 1 (SH3YL1) protein; SH3YL1 localizes ...
299-350 8.21e-09

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


Pssm-ID: 212775  Cd Length: 54  Bit Score: 51.24  E-value: 8.21e-09
                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|..
gi 115527076 299 QGLWDCHGDQPDELSFQRGDLIRILSKEYNMYGWWVGELNSLVGIVPKEYLT 350
Cdd:cd11841    3 TALYSFEGQQPCDLSFQAGDRITVLTRTDSQFDWWEGRLRGRVGIFPANYVS 54
PH1_PH_fungal cd13298
Fungal proteins Pleckstrin homology (PH) domain, repeat 1; The functions of these fungal ...
104-205 1.82e-08

Fungal proteins Pleckstrin homology (PH) domain, repeat 1; The functions of these fungal proteins are unknown, but they all contain 2 PH domains. This cd represents the first PH repeat. PH domains have diverse functions, but in general are involved in targeting proteins to the appropriate cellular location or in the interaction with a binding partner. They share little sequence conservation, but all have a common fold, which is electrostatically polarized. Less than 10% of PH domains bind phosphoinositide phosphates (PIPs) with high affinity and specificity. PH domains are distinguished from other PIP-binding domains by their specific high-affinity binding to PIPs with two vicinal phosphate groups: PtdIns(3,4)P2, PtdIns(4,5)P2 or PtdIns(3,4,5)P3 which results in targeting some PH domain proteins to the plasma membrane. A few display strong specificity in lipid binding. Any specificity is usually determined by loop regions or insertions in the N-terminus of the domain, which are not conserved across all PH domains. PH domains are found in cellular signaling proteins such as serine/threonine kinase, tyrosine kinases, regulators of G-proteins, endocytotic GTPases, adaptors, as well as cytoskeletal associated molecules and in lipid associated enzymes.


Pssm-ID: 270110  Cd Length: 106  Bit Score: 51.86  E-value: 1.82e-08
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 115527076 104 ELDNVIKQGYLEKKSKDHSFfgseWQKRWCVVSRGLFYYYANEKSKQPKGTFLIKGYgVRMAPHlrRDSKKESCFELTSQ 183
Cdd:cd13298    2 EFDRVLKSGYLLKRSRKTKN----WKKRWVVLRPCQLSYYKDEKEYKLRRVINLSEL-LAVAPL--KDKKRKNVFGIYTP 74
                         90       100
                 ....*....|....*....|..
gi 115527076 184 DrRSYEFTATSPAEARDWVDQI 205
Cdd:cd13298   75 S-KNLHFRATSEKDANEWVEAL 95
PH1_PLEKHH1_PLEKHH2 cd13282
Pleckstrin homology (PH) domain containing, family H (with MyTH4 domain) members 1 and 2 ...
110-214 2.56e-08

Pleckstrin homology (PH) domain containing, family H (with MyTH4 domain) members 1 and 2 (PLEKHH1) PH domain, repeat 1; PLEKHH1 and PLEKHH2 (also called PLEKHH1L) are thought to function in phospholipid binding and signal transduction. There are 3 Human PLEKHH genes: PLEKHH1, PLEKHH2, and PLEKHH3. There are many isoforms, the longest of which contain a FERM domain, a MyTH4 domain, two PH domains, a peroximal domain, a vacuolar domain, and a coiled coil stretch. The FERM domain has a cloverleaf tripart structure (FERM_N, FERM_M, FERM_C/N, alpha-, and C-lobe/A-lobe, B-lobe, C-lobe/F1, F2, F3). The C-lobe/F3 within the FERM domain is part of the PH domain family. PH domains have diverse functions, but in general are involved in targeting proteins to the appropriate cellular location or in the interaction with a binding partner. They share little sequence conservation, but all have a common fold, which is electrostatically polarized. Less than 10% of PH domains bind phosphoinositide phosphates (PIPs) with high affinity and specificity. PH domains are distinguished from other PIP-binding domains by their specific high-affinity binding to PIPs with two vicinal phosphate groups: PtdIns(3,4)P2, PtdIns(4,5)P2 or PtdIns(3,4,5)P3 which results in targeting some PH domain proteins to the plasma membrane. A few display strong specificity in lipid binding. Any specificity is usually determined by loop regions or insertions in the N-terminus of the domain, which are not conserved across all PH domains. PH domains are found in cellular signaling proteins such as serine/threonine kinase, tyrosine kinases, regulators of G-proteins, endocytotic GTPases, adaptors, as well as cytoskeletal associated molecules and in lipid associated enzymes.


Pssm-ID: 241436  Cd Length: 96  Bit Score: 51.14  E-value: 2.56e-08
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 115527076 110 KQGYLEK---KSKDhsffgseWQKRWCVVSRGLFYYYA--NEKSKQPKGTFLIKGYGvRMAPhlrrdSKKESCFELTSqD 184
Cdd:cd13282    1 KAGYLTKlggKVKT-------WKRRWFVLKNGELFYYKspNDVIRKPQGQIALDGSC-EIAR-----AEGAQTFEIVT-E 66
                         90       100       110
                 ....*....|....*....|....*....|
gi 115527076 185 RRSYEFTATSPAEARDWVDQISFLLKDLSS 214
Cdd:cd13282   67 KRTYYLTADSENDLDEWIRVIQNVLRRQAS 96
PH3_ARAP cd13256
ArfGAP with RhoGAP domain, ankyrin repeat and PH domain Pleckstrin homology (PH) domain, ...
114-205 3.56e-08

ArfGAP with RhoGAP domain, ankyrin repeat and PH domain Pleckstrin homology (PH) domain, repeat 3; ARAP proteins (also called centaurin delta) are phosphatidylinositol 3,4,5-trisphosphate-dependent GTPase-activating proteins that modulate actin cytoskeleton remodeling by regulating ARF and RHO family members. They bind phosphatidylinositol 3,4,5-trisphosphate (PtdIns(3,4,5)P3) and phosphatidylinositol 3,4-bisphosphate (PtdIns(3,4,5)P2) binding. There are 3 mammalian ARAP proteins: ARAP1, ARAP2, and ARAP3. All ARAP proteins contain a N-terminal SAM (sterile alpha motif) domain, 5 PH domains, an ArfGAP domain, 2 ankyrin domain, A RhoGap domain, and a Ras-associating domain. This hierarchy contains the third PH domain in ARAP. PH domains have diverse functions, but in general are involved in targeting proteins to the appropriate cellular location or in the interaction with a binding partner. They share little sequence conservation, but all have a common fold, which is electrostatically polarized. Less than 10% of PH domains bind phosphoinositide phosphates (PIPs) with high affinity and specificity. PH domains are distinguished from other PIP-binding domains by their specific high-affinity binding to PIPs with two vicinal phosphate groups: PtdIns(3,4)P2, PtdIns(4,5)P2 or PtdIns(3,4,5)P3 which results in targeting some PH domain proteins to the plasma membrane. A few display strong specificity in lipid binding. Any specificity is usually determined by loop regions or insertions in the N-terminus of the domain, which are not conserved across all PH domains. PH domains are found in cellular signaling proteins such as serine/threonine kinase, tyrosine kinases, regulators of G-proteins, endocytotic GTPases, adaptors, as well as cytoskeletal associated molecules and in lipid associated enzymes.


Pssm-ID: 270076  Cd Length: 110  Bit Score: 50.92  E-value: 3.56e-08
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 115527076 114 LEKKSKDhsffgsEWQKRWCVVSRGLFYYYANEKSKQPKGTFLIKGYgVRMA---PHLRRDSKKESCFELTSQDRRSYEF 190
Cdd:cd13256   19 LERRARE------EFSRRWCVLEDGFLSYYESERSPEPNGEIDVSEI-VCLAvspPDTHPGDGFPFTFELYLESERLYLF 91
                         90
                 ....*....|....*
gi 115527076 191 TATSPAEARDWVDQI 205
Cdd:cd13256   92 GLETAEALHEWVKAI 106
SH3_Intersectin_5 cd11840
Fifth Src homology 3 domain (or SH3E) of Intersectin; Intersectins (ITSNs) are adaptor ...
310-350 3.61e-08

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


Pssm-ID: 212774 [Multi-domain]  Cd Length: 53  Bit Score: 49.34  E-value: 3.61e-08
                         10        20        30        40
                 ....*....|....*....|....*....|....*....|.
gi 115527076 310 DELSFQRGDLIRILSKEYNmyGWWVGELNSLVGIVPKEYLT 350
Cdd:cd11840   14 DELSFQKGDIINVLSKDDP--DWWRGELNGQTGLFPSNYVE 52
PH-GRAM1_AGT26 cd13215
Autophagy-related protein 26/Sterol 3-beta-glucosyltransferase Pleckstrin homology (PH) domain, ...
106-205 4.34e-08

Autophagy-related protein 26/Sterol 3-beta-glucosyltransferase Pleckstrin homology (PH) domain, repeat 1; ATG26 (also called UGT51/UDP-glycosyltransferase 51), a member of the glycosyltransferase 28 family, resulting in the biosynthesis of sterol glucoside. ATG26 in decane metabolism and autophagy. There are 32 known autophagy-related (ATG) proteins, 17 are components of the core autophagic machinery essential for all autophagy-related pathways and 15 are the additional components required only for certain pathways or species. The core autophagic machinery includes 1) the ATG9 cycling system (ATG1, ATG2, ATG9, ATG13, ATG18, and ATG27), 2) the phosphatidylinositol 3-kinase complex (ATG6/VPS30, ATG14, VPS15, and ATG34), and 3) the ubiquitin-like protein system (ATG3, ATG4, ATG5, ATG7, ATG8, ATG10, ATG12, and ATG16). Less is known about how the core machinery is adapted or modulated with additional components to accommodate the nonselective sequestration of bulk cytosol (autophagosome formation) or selective sequestration of specific cargos (Cvt vesicle, pexophagosome, or bacteria-containing autophagosome formation). The pexophagosome-specific additions include the ATG30-ATG11-ATG17 receptor-adaptors complex, the coiled-coil protein ATG25, and the sterol glucosyltransferase ATG26. ATG26 is necessary for the degradation of medium peroxisomes. It contains 2 GRAM domains and a single PH domain. PH domains are only found in eukaryotes. They share little sequence conservation, but all have a common fold, which is electrostatically polarized. PH domains also have diverse functions. They are often involved in targeting proteins to the plasma membrane, but few display strong specificity in lipid binding. Any specificity is usually determined by loop regions or insertions in the N-terminus of the domain, which are not conserved across all PH domains. PH domains are found in cellular signaling proteins such as serine/threonine kinase, tyrosine kinases, regulators of G-proteins, endocytotic GTPases, adaptors, as well as cytoskeletal associated molecules and in lipid associated enzymes.


Pssm-ID: 275402  Cd Length: 116  Bit Score: 51.08  E-value: 4.34e-08
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 115527076 106 DNVIKQGYLEKKSKDHSFfgseWQKRWCVVSRGLFYYYANekSKQ---PKGTF-LIKGYGVRMAPHlrrDSKKESCFELT 181
Cdd:cd13215   19 GAVIKSGYLSKRSKRTLR----YTRYWFVLKGDTLSWYNS--STDlyfPAGTIdLRYATSIELSKS---NGEATTSFKIV 89
                         90       100
                 ....*....|....*....|....
gi 115527076 182 SQDRRsYEFTATSPAEARDWVDQI 205
Cdd:cd13215   90 TNSRT-YKFKADSETSADEWVKAL 112
SH3_MLK1-3 cd12059
Src Homology 3 domain of Mixed Lineage Kinases 1, 2, and 3; MLKs 1, 2, and 3 are Serine ...
297-351 4.80e-08

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


Pssm-ID: 212992 [Multi-domain]  Cd Length: 58  Bit Score: 48.99  E-value: 4.80e-08
                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|....*...
gi 115527076 297 YYQGLWDCHGDQPDELSFQRGDLIRILSKEYNMYG---WWVGELNSLVGIVPKEYLTT 351
Cdd:cd12059    1 VWTAVFDYEASAEDELTLRRGDRVEVLSKDSAVSGdegWWTGKINDRVGIFPSNYVTS 58
SH3_GRB2_like_C cd11805
C-terminal Src homology 3 domain of Growth factor receptor-bound protein 2 (GRB2) and related ...
299-350 5.20e-08

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


Pssm-ID: 212739 [Multi-domain]  Cd Length: 53  Bit Score: 48.78  E-value: 5.20e-08
                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|..
gi 115527076 299 QGLWDCHGDQPDELSFQRGDLIRILSKEYNmyGWWVGELNSLVGIVPKEYLT 350
Cdd:cd11805    3 QALYDFNPQEPGELEFRRGDIITVLDSSDP--DWWKGELRGRVGIFPANYVQ 52
PH_SKIP cd13309
SifA and kinesin-interacting protein Pleckstrin homology (PH) domain; SKIP (also called ...
110-201 5.63e-08

SifA and kinesin-interacting protein Pleckstrin homology (PH) domain; SKIP (also called PLEKHM2/Pleckstrin homology domain-containing family M member 2) is a soluble cytosolic protein that contains a RUN domain and a PH domain separated by a unstructured linker region. SKIP is a target of the Salmonella effector protein SifA and the SifA-SKIP complex regulates kinesin-1 on the bacterial vacuole. The PH domain of SKIP binds to the N-terminal region of SifA while the N-terminus of SKIP is proposed to bind the TPR domain of the kinesin light chain. The opposite side of the SKIP PH domain is proposed to bind phosphoinositides. TSifA, SKIP, SseJ, and RhoA family GTPases are also thought to promote host membrane tubulation. Recently, it was shown that the lysosomal GTPase Arl8 binds to the kinesin-1 linker SKIP and that both are required for the normal intracellular distribution of lysosomes. Interestingly, two kinesin light chain binding motifs (WD) in SKIP have now been identified to match a consensus sequence for a kinesin light chain binding site found in several proteins including calsyntenin-1/alcadein, caytaxin, and vaccinia virus A36. SKIP has also been shown to interact with Rab1A. PH domains have diverse functions, but in general are involved in targeting proteins to the appropriate cellular location or in the interaction with a binding partner. They share little sequence conservation, but all have a common fold, which is electrostatically polarized. Less than 10% of PH domains bind phosphoinositide phosphates (PIPs) with high affinity and specificity. PH domains are distinguished from other PIP-binding domains by their specific high-affinity binding to PIPs with two vicinal phosphate groups: PtdIns(3,4)P2, PtdIns(4,5)P2 or PtdIns(3,4,5)P3 which results in targeting some PH domain proteins to the plasma membrane. A few display strong specificity in lipid binding. Any specificity is usually determined by loop regions or insertions in the N-terminus of the domain, which are not conserved across all PH domains. PH domains are found in cellular signaling proteins such as serine/threonine kinase, tyrosine kinases, regulators of G-proteins, endocytotic GTPases, adaptors, as well as cytoskeletal associated molecules and in lipid associated enzymes.


Pssm-ID: 270119  Cd Length: 103  Bit Score: 50.07  E-value: 5.63e-08
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 115527076 110 KQGYLEKKSKDHSFFGSEWQKRWCVVSRGLFYYYANEKSKQPKGTFLIKGY---GVRMAPHLRRdskkESCFELTSQDRR 186
Cdd:cd13309    2 KEGMLMYKTGTSYLGGETWKPGYFLLKNGVLYQYPDRSDRLPLLSISLGGEqcgGCRRINNTER----PHTFELILTDRS 77
                         90
                 ....*....|....*
gi 115527076 187 SYEFTATSPAEARDW 201
Cdd:cd13309   78 SLELAAPDEYEASEW 92
PH_SWAP-70 cd13273
Switch-associated protein-70 Pleckstrin homology (PH) domain; SWAP-70 (also called ...
107-205 7.57e-08

Switch-associated protein-70 Pleckstrin homology (PH) domain; SWAP-70 (also called Differentially expressed in FDCP 6/DEF-6 or IRF4-binding protein) functions in cellular signal transduction pathways (in conjunction with Rac), regulates cell motility through actin rearrangement, and contributes to the transformation and invasion activity of mouse embryo fibroblasts. Metazoan SWAP-70 is found in B lymphocytes, mast cells, and in a variety of organs. Metazoan SWAP-70 contains an N-terminal EF-hand motif, a centrally located PH domain, and a C-terminal coiled-coil domain. The PH domain of Metazoan SWAP-70 contains a phosphoinositide-binding site and a nuclear localization signal (NLS), which localize SWAP-70 to the plasma membrane and nucleus, respectively. The NLS is a sequence of four Lys residues located at the N-terminus of the C-terminal a-helix; this is a unique characteristic of the Metazoan SWAP-70 PH domain. The SWAP-70 PH domain binds PtdIns(3,4,5)P3 and PtdIns(4,5)P2 embedded in lipid bilayer vesicles. There are additional plant SWAP70 proteins, but these are not included in this hierarchy. Rice SWAP70 (OsSWAP70) exhibits GEF activity toward the its Rho GTPase, OsRac1, and regulates chitin-induced production of reactive oxygen species and defense gene expression in rice. Arabidopsis SWAP70 (AtSWAP70) plays a role in both PAMP- and effector-triggered immunity. Plant SWAP70 contains both DH and PH domains, but their arrangement is the reverse of that in typical DH-PH-type Rho GEFs, wherein the DH domain is flanked by a C-terminal PH domain. PH domains have diverse functions, but in general are involved in targeting proteins to the appropriate cellular location or in the interaction with a binding partner. They share little sequence conservation, but all have a common fold, which is electrostatically polarized. Less than 10% of PH domains bind phosphoinositide phosphates (PIPs) with high affinity and specificity. PH domains are distinguished from other PIP-binding domains by their specific high-affinity binding to PIPs with two vicinal phosphate groups: PtdIns(3,4)P2, PtdIns(4,5)P2 or PtdIns(3,4,5)P3 which results in targeting some PH domain proteins to the plasma membrane. A few display strong specificity in lipid binding. Any specificity is usually determined by loop regions or insertions in the N-terminus of the domain, which are not conserved across all PH domains. PH domains are found in cellular signaling proteins such as serine/threonine kinase, tyrosine kinases, regulators of G-proteins, endocytotic GTPases, adaptors, as well as cytoskeletal associated molecules and in lipid associated enzymes.


Pssm-ID: 270092  Cd Length: 110  Bit Score: 49.99  E-value: 7.57e-08
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 115527076 107 NVIKQGYLEKKSkdHSFfgSEWQKRWCVVSRGLFYYYANEKSKQPKGTFLIKGYGvRMAPHLRRDSKKesCFELTSQDRR 186
Cdd:cd13273    7 DVIKKGYLWKKG--HLL--PTWTERWFVLKPNSLSYYKSEDLKEKKGEIALDSNC-CVESLPDREGKK--CRFLVKTPDK 79
                         90
                 ....*....|....*....
gi 115527076 187 SYEFTATSPAEARDWVDQI 205
Cdd:cd13273   80 TYELSASDHKTRQEWIAAI 98
SH3_Nostrin cd11823
Src homology 3 domain of Nitric Oxide Synthase TRaffic INducer; Nostrin is expressed in ...
301-357 8.00e-08

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: 48.49  E-value: 8.00e-08
                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|....*..
gi 115527076 301 LWDCHGDQPDELSFQRGDLIRILSKEYNmyGWWVGELNSLVGIVPKEYlttafeVEE 357
Cdd:cd11823    5 LYSYTANREDELSLQPGDIIEVHEKQDD--GWWLGELNGKKGIFPATY------VEE 53
PH2_MyoX cd13296
Myosin X Pleckstrin homology (PH) domain, repeat 2; MyoX, a MyTH-FERM myosin, is a molecular ...
110-206 9.43e-08

Myosin X Pleckstrin homology (PH) domain, repeat 2; MyoX, a MyTH-FERM myosin, is a molecular motor that has crucial functions in the transport and/or tethering of integrins in the actin-based extensions known as filopodia, microtubule binding, and in netrin-mediated axon guidance. It functions as a dimer. MyoX walks on bundles of actin, rather than single filaments, unlike the other unconventional myosins. MyoX is present in organisms ranging from humans to choanoflagellates, but not in Drosophila and Caenorhabditis elegans.MyoX consists of a N-terminal motor/head region, a neck made of 3 IQ motifs, and a tail consisting of a coiled-coil domain, a PEST region, 3 PH domains, a myosin tail homology 4 (MyTH4), and a FERM domain at its very C-terminus. The first PH domain in the MyoX tail is a split-PH domain, interupted by the second PH domain such that PH 1a and PH 1b flanks PH 2. The third PH domain (PH 3) follows the PH 1b domain. This cd contains the second PH repeat. PH domains have diverse functions, but in general are involved in targeting proteins to the appropriate cellular location or in the interaction with a binding partner. They share little sequence conservation, but all have a common fold, which is electrostatically polarized. Less than 10% of PH domains bind phosphoinositide phosphates (PIPs) with high affinity and specificity. PH domains are distinguished from other PIP-binding domains by their specific high-affinity binding to PIPs with two vicinal phosphate groups: PtdIns(3,4)P2, PtdIns(4,5)P2 or PtdIns(3,4,5)P3 which results in targeting some PH domain proteins to the plasma membrane. A few display strong specificity in lipid binding. Any specificity is usually determined by loop regions or insertions in the N-terminus of the domain, which are not conserved across all PH domains. PH domains are found in cellular signaling proteins such as serine/threonine kinase, tyrosine kinases, regulators of G-proteins, endocytotic GTPases, adaptors, as well as cytoskeletal associated molecules and in lipid associated enzymes.


Pssm-ID: 270108  Cd Length: 103  Bit Score: 49.77  E-value: 9.43e-08
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 115527076 110 KQGYLEKKSKDHSFFG-SEWQKRWCVVSRGLFYYYAN-EKSKQPKGTFlikgyGVRMAPHLRRDSKKESCFELTSQDRrS 187
Cdd:cd13296    1 KSGWLTKKGGGSSTLSrRNWKSRWFVLRDTVLKYYENdQEGEKLLGTI-----DIRSAKEIVDNDPKENRLSITTEER-T 74
                         90
                 ....*....|....*....
gi 115527076 188 YEFTATSPAEARDWVDQIS 206
Cdd:cd13296   75 YHLVAESPEDASQWVNVLT 93
SH3_Nephrocystin cd11770
Src Homology 3 domain of Nephrocystin (or Nephrocystin-1); Nephrocystin contains an SH3 domain ...
297-349 9.68e-08

Src Homology 3 domain of Nephrocystin (or Nephrocystin-1); Nephrocystin contains an SH3 domain involved in signaling pathways that regulate cell adhesion and cytoskeletal organization. It is a protein that in humans is associated with juvenile nephronophthisis, an inherited kidney disease characterized by renal fibrosis that lead to chronic renal failure in children. It is localized in cell-cell junctions in renal duct cells, and is known to interact with Ack1, an activated Cdc42-associated kinase. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 212704 [Multi-domain]  Cd Length: 54  Bit Score: 48.08  E-value: 9.68e-08
                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|....*
gi 115527076 297 YYQGLWDCHGDQPDELSFQRGDLIRILSKEYNmyGWWVGElNSL--VGIVPKEYL 349
Cdd:cd11770    1 LYEALSDFQAEQEGDLSFKKGEVLRIISKRAD--GWWLAE-NSKgnRGLVPKTYL 52
SH3_FCHSD_2 cd11762
Second Src Homology 3 domain of FCH and double SH3 domains proteins; This group is composed of ...
297-345 1.13e-07

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


Pssm-ID: 212696 [Multi-domain]  Cd Length: 57  Bit Score: 48.16  E-value: 1.13e-07
                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|.
gi 115527076 297 YYQGLWDCHGDQPDELSFQRGDLIRILSKEYNMY--GWWVGELNSLVGIVP 345
Cdd:cd11762    1 LVRALYDYEAQSDEELSFPEGAIIRILRKDDNGVddGWWEGEFNGRVGVFP 51
SH3_2 pfam07653
Variant SH3 domain; SH3 (Src homology 3) domains are often indicative of a protein involved in ...
297-349 1.38e-07

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


Pssm-ID: 429575 [Multi-domain]  Cd Length: 54  Bit Score: 47.59  E-value: 1.38e-07
                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|...
gi 115527076  297 YYQGLWDCHGDQPDELSFQRGDLIRILSKEYNmyGWWVGELNSLVGIVPKEYL 349
Cdd:pfam07653   1 YGRVIFDYVGTDKNGLTLKKGDVVKVLGKDND--GWWEGETGGRVGLVPSTAV 51
SH3_EFS cd12003
Src homology 3 domain of CAS (Crk-Associated Substrate) scaffolding protein family member, ...
299-345 1.55e-07

Src homology 3 domain of CAS (Crk-Associated Substrate) scaffolding protein family member, Embryonal Fyn-associated Substrate; EFS is also called HEFS, CASS3 (Cas scaffolding protein family member 3) or SIN (Src-interacting protein). It was identified based on interactions with the Src kinases, Fyn and Yes. It plays a role in thymocyte development and acts as a negative regulator of T cell proliferation. CAS proteins function as molecular scaffolds to regulate protein complexes that are involved in many cellular processes. They share a common domain structure that includes an N-terminal SH3 domain, an unstructured substrate domain that contains many YxxP motifs, a serine-rich four-helix bundle, and a FAT-like C-terminal domain. The SH3 domain of CAS proteins binds to diverse partners including FAK, FRNK, Pyk2, PTP-PEST, DOCK180, among others. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 212936  Cd Length: 62  Bit Score: 47.96  E-value: 1.55e-07
                         10        20        30        40
                 ....*....|....*....|....*....|....*....|....*...
gi 115527076 299 QGLWDCHGDQPDELSFQRGDLIRILSKEY-NMYGWWVGELNSLVGIVP 345
Cdd:cd12003    4 KALYDNAAESPEELSFRRGDVLMVLKREHgSLPGWWLCSLHGQQGIAP 51
SH3_MLK4 cd12058
Src Homology 3 domain of Mixed Lineage Kinase 4; MLK4 is a Serine/Threonine Kinase (STK), ...
298-350 1.91e-07

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


Pssm-ID: 212991 [Multi-domain]  Cd Length: 58  Bit Score: 47.63  E-value: 1.91e-07
                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|....*.
gi 115527076 298 YQGLWDCHGDQPDELSFQRGDLIRILSKEYNMY---GWWVGELNSLVGIVPKEYLT 350
Cdd:cd12058    2 WTALYDYEASGEDELSLRRGDVVEVLSQDAAVSgddGWWAGKIRHRLGIFPANYVT 57
PH_DOCK-D cd13267
Dedicator of cytokinesis-D subfamily Pleckstrin homology (PH) domain; DOCK-D subfamily (also ...
108-202 1.93e-07

Dedicator of cytokinesis-D subfamily Pleckstrin homology (PH) domain; DOCK-D subfamily (also called Zizimin subfamily) consists of Dock9/Zizimin1, Dock10/Zizimin3, and Dock11/Zizimin2. DOCK-D has a N-terminal DUF3398 domain, a PH-like domain, a Dock Homology Region 1, DHR1 (also called CZH1), a C2 domain, and a C-terminal DHR2 domain (also called CZH2). Zizimin1 is enriched in the brain, lung, and kidney; zizimin2 is found in B and T lymphocytes, and zizimin3 is enriched in brain, lung, spleen and thymus. Zizimin1 functions in autoinhibition and membrane targeting. Zizimin2 is an immune-related and age-regulated guanine nucleotide exchange factor, which facilitates filopodial formation through activation of Cdc42, which results in activation of cell migration. No function has been determined for Zizimin3 to date. The N-terminal half of zizimin1 binds to the GEF domain through three distinct areas, including CZH1, to inhibit the interaction with Cdc42. In addition its PH domain binds phosphoinositides and mediates zizimin1 membrane targeting. DOCK is a family of proteins involved in intracellular signalling networks. They act as guanine nucleotide exchange factors for small G proteins of the Rho family, such as Rac and Cdc42. There are 4 subfamilies of DOCK family proteins based on their sequence homology: A-D. PH domains have diverse functions, but in general are involved in targeting proteins to the appropriate cellular location or in the interaction with a binding partner. They share little sequence conservation, but all have a common fold, which is electrostatically polarized. Less than 10% of PH domains bind phosphoinositide phosphates (PIPs) with high affinity and specificity. PH domains are distinguished from other PIP-binding domains by their specific high-affinity binding to PIPs with two vicinal phosphate groups: PtdIns(3,4)P2, PtdIns(4,5)P2 or PtdIns(3,4,5)P3 which results in targeting some PH domain proteins to the plasma membrane. A few display strong specificity in lipid binding. Any specificity is usually determined by loop regions or insertions in the N-terminus of the domain, which are not conserved across all PH domains. PH domains are found in cellular signaling proteins such as serine/threonine kinase, tyrosine kinases, regulators of G-proteins, endocytotic GTPases, adaptors, as well as cytoskeletal associated molecules and in lipid associated enzymes.


Pssm-ID: 270087  Cd Length: 126  Bit Score: 49.25  E-value: 1.93e-07
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 115527076 108 VIKQGYLEKKSKDHSFFGS-----EWQKRWCVVSR---GLFY--YYANEKSKQPKGT-FLIKGYGVRMAPHLRRdskkeS 176
Cdd:cd13267    6 ITKEGYLYKGPENSSDSFIslamkSFKRRFFHLKQlvdGSYIleFYKDEKKKEAKGTiFLDSCTGVVQNSKRRK-----F 80
                         90       100
                 ....*....|....*....|....*.
gi 115527076 177 CFELTSQDRRSYEFTATSPAEARDWV 202
Cdd:cd13267   81 CFELRMQDKKSYVLAAESEAEMDEWI 106
PH1_ARAP cd13253
ArfGAP with RhoGAP domain, ankyrin repeat and PH domain Pleckstrin homology (PH) domain, ...
109-202 2.12e-07

ArfGAP with RhoGAP domain, ankyrin repeat and PH domain Pleckstrin homology (PH) domain, repeat 1; ARAP proteins (also called centaurin delta) are phosphatidylinositol 3,4,5-trisphosphate-dependent GTPase-activating proteins that modulate actin cytoskeleton remodeling by regulating ARF and RHO family members. They bind phosphatidylinositol 3,4,5-trisphosphate (PtdIns(3,4,5)P3) and phosphatidylinositol 3,4-bisphosphate (PtdIns(3,4,5)P2) binding. There are 3 mammalian ARAP proteins: ARAP1, ARAP2, and ARAP3. All ARAP proteins contain a N-terminal SAM (sterile alpha motif) domain, 5 PH domains, an ArfGAP domain, 2 ankyrin domain, A RhoGap domain, and a Ras-associating domain. This hierarchy contains the first PH domain in ARAP. PH domains have diverse functions, but in general are involved in targeting proteins to the appropriate cellular location or in the interaction with a binding partner. They share little sequence conservation, but all have a common fold, which is electrostatically polarized. Less than 10% of PH domains bind phosphoinositide phosphates (PIPs) with high affinity and specificity. PH domains are distinguished from other PIP-binding domains by their specific high-affinity binding to PIPs with two vicinal phosphate groups: PtdIns(3,4)P2, PtdIns(4,5)P2 or PtdIns(3,4,5)P3 which results in targeting some PH domain proteins to the plasma membrane. A few display strong specificity in lipid binding. Any specificity is usually determined by loop regions or insertions in the N-terminus of the domain, which are not conserved across all PH domains. PH domains are found in cellular signaling proteins such as serine/threonine kinase, tyrosine kinases, regulators of G-proteins, endocytotic GTPases, adaptors, as well as cytoskeletal associated molecules and in lipid associated enzymes.


Pssm-ID: 270073  Cd Length: 94  Bit Score: 48.54  E-value: 2.12e-07
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 115527076 109 IKQGYLEKKSKDHSFFGseWQKRWCVVSRGLFYYYANEKSKQPKGtfLIKGYGVRMAPhlrrdSKKESCFEL-TSQdrRS 187
Cdd:cd13253    1 IKSGYLDKQGGQGNNKG--FQKRWVVFDGLSLRYFDSEKDAYSKR--IIPLSAISTVR-----AVGDNKFELvTTN--RT 69
                         90
                 ....*....|....*
gi 115527076 188 YEFTATSPAEARDWV 202
Cdd:cd13253   70 FVFRAESDDERNLWC 84
SH3_GRB2_N cd11946
N-terminal Src homology 3 domain of Growth factor receptor-bound protein 2; GRB2 is a critical ...
310-349 2.39e-07

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


Pssm-ID: 212879 [Multi-domain]  Cd Length: 56  Bit Score: 46.94  E-value: 2.39e-07
                         10        20        30        40
                 ....*....|....*....|....*....|....*....|
gi 115527076 310 DELSFQRGDLIRILSKEYNMyGWWVGELNSLVGIVPKEYL 349
Cdd:cd11946   15 DELSFKRGDILKVLNEECDQ-NWYKAELNGKDGFIPKNYI 53
PH_DAPP1 cd10573
Dual Adaptor for Phosphotyrosine and 3-Phosphoinositides Pleckstrin homology (PH) domain; ...
110-209 2.44e-07

Dual Adaptor for Phosphotyrosine and 3-Phosphoinositides Pleckstrin homology (PH) domain; DAPP1 (also known as PHISH/3' phosphoinositide-interacting SH2 domain-containing protein or Bam32) plays a role in B-cell activation and has potential roles in T-cell and mast cell function. DAPP1 promotes B cell receptor (BCR) induced activation of Rho GTPases Rac1 and Cdc42, which feed into mitogen-activated protein kinases (MAPK) activation pathways and affect cytoskeletal rearrangement. DAPP1can also regulate BCR-induced activation of extracellular signal-regulated kinase (ERK), and c-jun NH2-terminal kinase (JNK). DAPP1 contains an N-terminal SH2 domain and a C-terminal pleckstrin homology (PH) domain with a single tyrosine phosphorylation site located centrally. DAPP1 binds strongly to both PtdIns(3,4,5)P3 and PtdIns(3,4)P2. The PH domain is essential for plasma membrane recruitment of PI3K upon cell activation. PH domains have diverse functions, but in general are involved in targeting proteins to the appropriate cellular location or in the interaction with a binding partner. They share little sequence conservation, but all have a common fold, which is electrostatically polarized. Less than 10% of PH domains bind phosphoinositide phosphates (PIPs) with high affinity and specificity. PH domains are distinguished from other PIP-binding domains by their specific high-affinity binding to PIPs with two vicinal phosphate groups: PtdIns(3,4)P2, PtdIns(4,5)P2 or PtdIns(3,4,5)P3 which results in targeting some PH domain proteins to the plasma membrane. A few display strong specificity in lipid binding. Any specificity is usually determined by loop regions or insertions in the N-terminus of the domain, which are not conserved across all PH domains. PH domains are found in cellular signaling proteins such as serine/threonine kinase, tyrosine kinases, regulators of G-proteins, endocytotic GTPases, adaptors, as well as cytoskeletal associated molecules and in lipid associated enzymes.


Pssm-ID: 269977 [Multi-domain]  Cd Length: 96  Bit Score: 48.09  E-value: 2.44e-07
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 115527076 110 KQGYLEKKSKdhsfFGSEWQKRWCVVSRGLFYYYANEKSKQPkgtflIKGYGVRMAPHLRRD--SKKESCFELTSQDRRS 187
Cdd:cd10573    5 KEGYLTKLGG----IVKNWKTRWFVLRRNELKYFKTRGDTKP-----IRVLDLRECSSVQRDysQGKVNCFCLVFPERTF 75
                         90       100
                 ....*....|....*....|..
gi 115527076 188 YEFtATSPAEARDWVDQISFLL 209
Cdd:cd10573   76 YMY-ANTEEEADEWVKLLKWKL 96
PH_ACAP cd13250
ArfGAP with coiled-coil, ankyrin repeat and PH domains Pleckstrin homology (PH) domain; ACAP ...
110-205 3.06e-07

ArfGAP with coiled-coil, ankyrin repeat and PH domains Pleckstrin homology (PH) domain; ACAP (also called centaurin beta) functions both as a Rab35 effector and as an Arf6-GTPase-activating protein (GAP) by which it controls actin remodeling and membrane trafficking. ACAP contain an NH2-terminal bin/amphiphysin/Rvs (BAR) domain, a phospholipid-binding domain, a PH domain, a GAP domain, and four ankyrin repeats. The AZAPs constitute a family of Arf GAPs that are characterized by an NH2-terminal pleckstrin homology (PH) domain and a central Arf GAP domain followed by two or more ankyrin repeats. On the basis of sequence and domain organization, the AZAP family is further subdivided into four subfamilies: 1) the ACAPs contain an NH2-terminal bin/amphiphysin/Rvs (BAR) domain (a phospholipid-binding domain that is thought to sense membrane curvature), a single PH domain followed by the GAP domain, and four ankyrin repeats; 2) the ASAPs also contain an NH2-terminal BAR domain, the tandem PH domain/GAP domain, three ankyrin repeats, two proline-rich regions, and a COOH-terminal Src homology 3 domain; 3) the AGAPs contain an NH2-terminal GTPase-like domain (GLD), a split PH domain, and the GAP domain followed by four ankyrin repeats; and 4) the ARAPs contain both an Arf GAP domain and a Rho GAP domain, as well as an NH2-terminal sterile-a motif (SAM), a proline-rich region, a GTPase-binding domain, and five PH domains. PMID 18003747 and 19055940 Centaurin can bind to phosphatidlyinositol (3,4,5)P3. PH domains have diverse functions, but in general are involved in targeting proteins to the appropriate cellular location or in the interaction with a binding partner. They share little sequence conservation, but all have a common fold, which is electrostatically polarized. Less than 10% of PH domains bind phosphoinositide phosphates (PIPs) with high affinity and specificity. PH domains are distinguished from other PIP-binding domains by their specific high-affinity binding to PIPs with two vicinal phosphate groups: PtdIns(3,4)P2, PtdIns(4,5)P2 or PtdIns(3,4,5)P3 which results in targeting some PH domain proteins to the plasma membrane. A few display strong specificity in lipid binding. Any specificity is usually determined by loop regions or insertions in the N-terminus of the domain, which are not conserved across all PH domains. PH domains are found in cellular signaling proteins such as serine/threonine kinase, tyrosine kinases, regulators of G-proteins, endocytotic GTPases, adaptors, as well as cytoskeletal associated molecules and in lipid associated enzymes.


Pssm-ID: 270070  Cd Length: 98  Bit Score: 47.98  E-value: 3.06e-07
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 115527076 110 KQGYLEKKSkdHSFFGSeWQKRWCVVSRGLFYYYANEKSKQPKgtflikgygvRMAPHLRRDSKKES-------CFELTS 182
Cdd:cd13250    1 KEGYLFKRS--SNAFKT-WKRRWFSLQNGQLYYQKRDKKDEPT----------VMVEDLRLCTVKPTedsdrrfCFEVIS 67
                         90       100
                 ....*....|....*....|...
gi 115527076 183 QDrRSYEFTATSPAEARDWVDQI 205
Cdd:cd13250   68 PT-KSYMLQAESEEDRQAWIQAI 89
SH3_OSTF1 cd11772
Src Homology 3 domain of metazoan osteoclast stimulating factor 1; OSTF1, also named OSF or ...
298-351 3.16e-07

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


Pssm-ID: 212706 [Multi-domain]  Cd Length: 53  Bit Score: 46.52  E-value: 3.16e-07
                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|....
gi 115527076 298 YQGLWDCHGDQPDELSFQRGDLIRILSKEYNmyGWWVGELNSLVGIVPKEYLTT 351
Cdd:cd11772    2 FRALYDYEAQHPDELSFEEGDLLYISDKSDP--NWWKATCGGKTGLIPSNYVEE 53
SH3_MLK cd11876
Src Homology 3 domain of Mixed Lineage Kinases; MLKs are Serine/Threonine Kinases (STKs), ...
302-350 3.29e-07

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


Pssm-ID: 212809 [Multi-domain]  Cd Length: 58  Bit Score: 46.74  E-value: 3.29e-07
                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|..
gi 115527076 302 WDCHGDqpDELSFQRGDLIRILSKEYNMYG---WWVGELNSLVGIVPKEYLT 350
Cdd:cd11876    8 YDARGE--DELTLRRGQPVEVLSKDAAVSGdegWWTGKIGDKVGIFPSNYVA 57
PH_AGAP cd01250
Arf-GAP with GTPase, ANK repeat and PH domain-containing protein Pleckstrin homology (PH) ...
109-205 3.67e-07

Arf-GAP with GTPase, ANK repeat and PH domain-containing protein Pleckstrin homology (PH) domain; AGAP (also called centaurin gamma; PIKE/Phosphatidylinositol-3-kinase enhancer) reside mainly in the nucleus and are known to activate phosphoinositide 3-kinase, a key regulator of cell proliferation, motility and vesicular trafficking. There are 3 isoforms of AGAP (PIKE-A, PIKE-L, and PIKE-S) the longest of which PIKE-L consists of N-terminal proline rich domains (PRDs), followed by a GTPase domain, a split PH domain (PHN and PHC), an ArfGAP domain and two ankyrin repeats. PIKE-S terminates after the PHN domain and PIKE-A is missing the PRD region. Centaurin binds phosphatidlyinositol (3,4,5)P3. PH domains have diverse functions, but in general are involved in targeting proteins to the appropriate cellular location or in the interaction with a binding partner. They share little sequence conservation, but all have a common fold, which is electrostatically polarized. Less than 10% of PH domains bind phosphoinositide phosphates (PIPs) with high affinity and specificity. PH domains are distinguished from other PIP-binding domains by their specific high-affinity binding to PIPs with two vicinal phosphate groups: PtdIns(3,4)P2, PtdIns(4,5)P2 or PtdIns(3,4,5)P3 which results in targeting some PH domain proteins to the plasma membrane. A few display strong specificity in lipid binding. Any specificity is usually determined by loop regions or insertions in the N-terminus of the domain, which are not conserved across all PH domains. PH domains are found in cellular signaling proteins such as serine/threonine kinase, tyrosine kinases, regulators of G-proteins, endocytotic GTPases, adaptors, as well as cytoskeletal associated molecules and in lipid associated enzymes.


Pssm-ID: 241281  Cd Length: 114  Bit Score: 48.09  E-value: 3.67e-07
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 115527076 109 IKQGYLEKKSKDHsfFGSEWQ-KRWCVVSRGLFYYYANEK----SKQPKGTFLIKgYGVRMA-PHLRRDSKKESC-FELT 181
Cdd:cd01250    5 IKQGYLYKRSSKS--LNKEWKkKYVTLCDDGRLTYHPSLHdymeNVHGKEIDLLR-TTVKVPgKRPPRASSKSAFeFIIV 81
                         90       100
                 ....*....|....*....|....*
gi 115527076 182 SQDRRSYEFTATSpAEARD-WVDQI 205
Cdd:cd01250   82 SLDGKQWHFEAAS-SEERDeWVQAI 105
SH3_FCHSD2_2 cd11894
Second Src Homology 3 domain of FCH and double SH3 domains protein 2; FCHSD2 has a domain ...
297-345 4.54e-07

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


Pssm-ID: 212827  Cd Length: 56  Bit Score: 46.47  E-value: 4.54e-07
                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|
gi 115527076 297 YYQGLWDCHGDQPDELSFQRGDLIRILSKEYNM-YGWWVGELNSLVGIVP 345
Cdd:cd11894    1 FVKALYDYEGQTDDELSFPEGAIIRILNKENQDdDGFWEGEFNGRIGVFP 50
SH3_1 pfam00018
SH3 domain; SH3 (Src homology 3) domains are often indicative of a protein involved in signal ...
301-345 5.67e-07

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: 45.66  E-value: 5.67e-07
                          10        20        30        40
                  ....*....|....*....|....*....|....*....|....*.
gi 115527076  301 LWDCHGDQPDELSFQRGDLIRILSKEYNmyGWWVGELNSL-VGIVP 345
Cdd:pfam00018   3 LYDYTAQEPDELSFKKGDIIIVLEKSED--GWWKGRNKGGkEGLIP 46
PH_ASAP cd13251
ArfGAP with SH3 domain, ankyrin repeat and PH domain Pleckstrin homology (PH) domain; ASAPs ...
110-202 6.48e-07

ArfGAP with SH3 domain, ankyrin repeat and PH domain Pleckstrin homology (PH) domain; ASAPs (ASAP1, ASAP2, and ASAP3) function as an Arf-specific GAPs, participates in rhodopsin trafficking, is associated with tumor cell metastasis, modulates phagocytosis, promotes cell proliferation, facilitates vesicle budding, Golgi exocytosis, and regulates vesicle coat assembly via a Bin/Amphiphysin/Rvs domain. ASAPs contain an NH2-terminal BAR domain, a tandem PH domain/GAP domain, three ankyrin repeats, two proline-rich regions, and a COOH-terminal Src homology 3 (SH3) domain. PH domains have diverse functions, but in general are involved in targeting proteins to the appropriate cellular location or in the interaction with a binding partner. They share little sequence conservation, but all have a common fold, which is electrostatically polarized. Less than 10% of PH domains bind phosphoinositide phosphates (PIPs) with high affinity and specificity. PH domains are distinguished from other PIP-binding domains by their specific high-affinity binding to PIPs with two vicinal phosphate groups: PtdIns(3,4)P2, PtdIns(4,5)P2 or PtdIns(3,4,5)P3 which results in targeting some PH domain proteins to the plasma membrane. A few display strong specificity in lipid binding. Any specificity is usually determined by loop regions or insertions in the N-terminus of the domain, which are not conserved across all PH domains. PH domains are found in cellular signaling proteins such as serine/threonine kinase, tyrosine kinases, regulators of G-proteins, endocytotic GTPases, adaptors, as well as cytoskeletal associated molecules and in lipid associated enzymes.


Pssm-ID: 270071  Cd Length: 108  Bit Score: 47.36  E-value: 6.48e-07
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 115527076 110 KQGYLEKKSKdhSFFGSEWQKRWCVVSRGLFYYYANEKSKQPKGTFLIKgygvrMAPHLRRDSKKesCFELTSQDrRSYE 189
Cdd:cd13251   12 KSGYLLKKSE--GKIRKVWQKRRCSIKDGFLTISHADENKPPAKLNLLT-----CQVKLVPEDKK--CFDLISHN-RTYH 81
                         90
                 ....*....|...
gi 115527076 190 FTATSPAEARDWV 202
Cdd:cd13251   82 FQAEDENDANAWM 94
SH3_CD2AP_3 cd12056
Third Src Homology 3 domain (SH3C) of CD2-associated protein; CD2AP, also called CMS (Cas ...
297-348 6.75e-07

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


Pssm-ID: 212989 [Multi-domain]  Cd Length: 57  Bit Score: 45.97  E-value: 6.75e-07
                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|..
gi 115527076 297 YYQGLWDCHGDQPDELSFQRGDLIRILSKEYNMYGWWVGELNSLVGIVPKEY 348
Cdd:cd12056    3 YCKALFHYEGTNEDELDFKEGEIILIISKDTGEPGWWKGELNGKEGVFPDNF 54
SH3_9 pfam14604
Variant SH3 domain;
309-350 8.29e-07

Variant SH3 domain;


Pssm-ID: 434066 [Multi-domain]  Cd Length: 49  Bit Score: 45.30  E-value: 8.29e-07
                          10        20        30        40
                  ....*....|....*....|....*....|....*....|..
gi 115527076  309 PDELSFQRGDLIRILSKEYNmyGWWVGELNSLVGIVPKEYLT 350
Cdd:pfam14604  10 DDELSLQRGDVITVIEESED--GWWEGINTGRTGLVPANYVE 49
PH1_Pleckstrin_2 cd13301
Pleckstrin 2 Pleckstrin homology (PH) domain, repeat 1; Pleckstrin is a protein found in ...
108-214 8.45e-07

Pleckstrin 2 Pleckstrin homology (PH) domain, repeat 1; Pleckstrin is a protein found in platelets. This name is derived from platelet and leukocyte C kinase substrate and the KSTR string of amino acids. Pleckstrin 2 contains two PH domains and a DEP (dishvelled, egl-10, and pleckstrin) domain. Unlike pleckstrin 1, pleckstrin 2 does not contain obvious sites of PKC phosphorylation. Pleckstrin 2 plays a role in actin rearrangement, large lamellipodia and peripheral ruffle formation, and may help orchestrate cytoskeletal arrangement. The PH domains of pleckstrin 2 are thought to contribute to lamellipodia formation. This cd contains the first PH domain repeat. PH domains have diverse functions, but in general are involved in targeting proteins to the appropriate cellular location or in the interaction with a binding partner. They share little sequence conservation, but all have a common fold, which is electrostatically polarized. Less than 10% of PH domains bind phosphoinositide phosphates (PIPs) with high affinity and specificity. PH domains are distinguished from other PIP-binding domains by their specific high-affinity binding to PIPs with two vicinal phosphate groups: PtdIns(3,4)P2, PtdIns(4,5)P2 or PtdIns(3,4,5)P3 which results in targeting some PH domain proteins to the plasma membrane. A few display strong specificity in lipid binding. Any specificity is usually determined by loop regions or insertions in the N-terminus of the domain, which are not conserved across all PH domains. PH domains are found in cellular signaling proteins such as serine/threonine kinase, tyrosine kinases, regulators of G-proteins, endocytotic GTPases, adaptors, as well as cytoskeletal associated molecules and in lipid associated enzymes.


Pssm-ID: 270113  Cd Length: 108  Bit Score: 46.98  E-value: 8.45e-07
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 115527076 108 VIKQGYLEKK-SKDHSffgseWQKRWCVVSRGLFYYYANEKSKQPKGTFLIKGYGVrMAPHLRRDsKKESCFELTSQDRR 186
Cdd:cd13301    3 IIKEGYLVKKgHVVNN-----WKARWFVLKEDGLEYYKKKTDSSPKGMIPLKGCTI-TSPCLEYG-KRPLVFKLTTAKGQ 75
                         90       100
                 ....*....|....*....|....*...
gi 115527076 187 SYEFTATSPAEARDWVDQISFLLKDLSS 214
Cdd:cd13301   76 EHFFQACSREERDAWAKDITKAITCLEG 103
SH3_CAS cd11844
Src homology 3 domain of CAS (Crk-Associated Substrate) scaffolding proteins; CAS proteins ...
301-345 9.11e-07

Src homology 3 domain of CAS (Crk-Associated Substrate) scaffolding proteins; CAS proteins function as molecular scaffolds to regulate protein complexes that are involved in many cellular processes including migration, chemotaxis, apoptosis, differentiation, and progenitor cell function. They mediate the signaling of integrins at focal adhesions where they localize, and thus, regulate cell invasion and survival. Over-expression of these proteins is implicated in poor prognosis, increased metastasis, and resistance to chemotherapeutics in many cancers such as breast, lung, melanoma, and glioblastoma. CAS proteins have also been linked to the pathogenesis of inflammatory disorders, Alzheimer's, Parkinson's, and developmental defects. They share a common domain structure that includes an N-terminal SH3 domain, an unstructured substrate domain that contains many YxxP motifs, a serine-rich four-helix bundle, and a FAT-like C-terminal domain. Vertebrates contain four CAS proteins: BCAR1 (or p130Cas), NEDD9 (or HEF1), EFS (or SIN), and CASS4 (or HEPL). The SH3 domain of CAS proteins binds to diverse partners including FAK, FRNK, Pyk2, PTP-PEST, DOCK180, among others. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 212778  Cd Length: 56  Bit Score: 45.41  E-value: 9.11e-07
                         10        20        30        40
                 ....*....|....*....|....*....|....*....|....*.
gi 115527076 301 LWDCHGDQPDELSFQRGDLIRILSKEYNMY-GWWVGELNSLVGIVP 345
Cdd:cd11844    5 LYDNVAESPDELAFRRGDILTVLEQNTAGLeGWWLCSLRGRQGIAP 50
PH_AtPH1 cd13276
Arabidopsis thaliana Pleckstrin homolog (PH) 1 (AtPH1) PH domain; AtPH1 is expressed in all ...
110-205 9.26e-07

Arabidopsis thaliana Pleckstrin homolog (PH) 1 (AtPH1) PH domain; AtPH1 is expressed in all plant tissue and is proposed to be the plant homolog of human pleckstrin. Pleckstrin consists of two PH domains separated by a linker region, while AtPH has a single PH domain with a short N-terminal extension. AtPH1 binds PtdIns3P specifically and is thought to be an adaptor molecule since it has no obvious catalytic functions. PH domains have diverse functions, but in general are involved in targeting proteins to the appropriate cellular location or in the interaction with a binding partner. They share little sequence conservation, but all have a common fold, which is electrostatically polarized. Less than 10% of PH domains bind phosphoinositide phosphates (PIPs) with high affinity and specificity. PH domains are distinguished from other PIP-binding domains by their specific high-affinity binding to PIPs with two vicinal phosphate groups: PtdIns(3,4)P2, PtdIns(4,5)P2 or PtdIns(3,4,5)P3 which results in targeting some PH domain proteins to the plasma membrane. A few display strong specificity in lipid binding. Any specificity is usually determined by loop regions or insertions in the N-terminus of the domain, which are not conserved across all PH domains. PH domains are found in cellular signaling proteins such as serine/threonine kinase, tyrosine kinases, regulators of G-proteins, endocytotic GTPases, adaptors, as well as cytoskeletal associated molecules and in lipid associated enzymes.


Pssm-ID: 270095  Cd Length: 106  Bit Score: 46.93  E-value: 9.26e-07
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 115527076 110 KQGYLEKKSKdhsfFGSEWQKRWCVVSRGLFYYYANEK---SKQPKGT-FLIKGYGVRMAphlRRDSKKESCFELTSQDR 185
Cdd:cd13276    1 KAGWLEKQGE----FIKTWRRRWFVLKQGKLFWFKEPDvtpYSKPRGViDLSKCLTVKSA---EDATNKENAFELSTPEE 73
                         90       100
                 ....*....|....*....|
gi 115527076 186 RSYeFTATSPAEARDWVDQI 205
Cdd:cd13276   74 TFY-FIADNEKEKEEWIGAI 92
SH3_iASPP cd11952
Src Homology 3 (SH3) domain of Inhibitor of ASPP protein (iASPP); iASPP, also called ...
301-349 9.82e-07

Src Homology 3 (SH3) domain of Inhibitor of ASPP protein (iASPP); iASPP, also called RelA-associated inhibitor (RAI), is an oncoprotein that inhibits the apoptotic transactivation potential of p53. It is upregulated in human breast cancers expressing wild-type p53, in acute leukemias regardless of the p53 mutation status, as well as in ovarian cancer where it is associated with poor patient outcome and chemoresistance. iASPP is also a binding partner and negative regulator of p65RelA, which promotes cell proliferation and inhibits apoptosis; p65RelA has the opposite effect on cell growth compared to the p53 family. It contains a proline-rich region, four ankyrin (ANK) repeats, and an SH3 domain at its C-terminal half. The SH3 domain and the ANK repeats of iASPP contribute to the p53 binding site; they bind to the DNA binding domain of p53. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 212885 [Multi-domain]  Cd Length: 56  Bit Score: 45.30  E-value: 9.82e-07
                         10        20        30        40
                 ....*....|....*....|....*....|....*....|....*....
gi 115527076 301 LWDCHGDQPDELSFQRGDLIRILSKEYNMYGWWVGELNSLVGIVPKEYL 349
Cdd:cd11952    6 LWDYSAEFPDELSFKEGDMVTVLRKDGEGTDWWWASLCGREGYVPRNYF 54
SH3_GRAF-like cd11882
Src Homology 3 domain of GTPase Regulator Associated with Focal adhesion kinase and similar ...
301-348 1.04e-06

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: 45.36  E-value: 1.04e-06
                         10        20        30        40
                 ....*....|....*....|....*....|....*....|....*...
gi 115527076 301 LWDCHGDQPDELSFQRGDLIrILSKEYNMYGWWVGELNSLVGIVPKEY 348
Cdd:cd11882    5 LYACKAEDESELSFEPGQII-TNVQPSDEPGWLEGTLNGRTGLIPENY 51
SH3_PSTPIP1 cd11824
Src homology 3 domain of Proline-Serine-Threonine Phosphatase-Interacting Protein 1; PSTPIP1, ...
298-350 1.10e-06

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


Pssm-ID: 212758 [Multi-domain]  Cd Length: 53  Bit Score: 45.06  E-value: 1.10e-06
                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|...
gi 115527076 298 YQGLWDCHGDQPDELSFQRGDLIRILSKEYNmyGWWVGELNSLVGIVPKEYLT 350
Cdd:cd11824    2 YSVLYDYTAQEDDELSISKGDVVAVIEKGED--GWWTVERNGQKGLVPGTYLE 52
SH3_srGAP4 cd11956
Src homology 3 domain of Slit-Robo GTPase Activating Protein 4; srGAP4, also called ARHGAP4, ...
301-350 1.11e-06

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


Pssm-ID: 212889 [Multi-domain]  Cd Length: 55  Bit Score: 45.22  E-value: 1.11e-06
                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|
gi 115527076 301 LWDCHGDQPDELSFQRGDLIRILSKEYNmyGWWVGELNSLVGIVPKEYLT 350
Cdd:cd11956    7 CFDYTGRTAQELSFKRGDVLLLHSKASS--DWWRGEHNGMRGLIPHKYIS 54
SH3_Intersectin1_5 cd11995
Fifth Src homology 3 domain (or SH3E) of Intersectin-1; Intersectin-1 (ITSN1) is an adaptor ...
300-349 1.81e-06

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


Pssm-ID: 212928 [Multi-domain]  Cd Length: 54  Bit Score: 44.56  E-value: 1.81e-06
                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|
gi 115527076 300 GLWDCHGDQPDELSFQRGDLIRILSKEYNmyGWWVGELNSLVGIVPKEYL 349
Cdd:cd11995    5 GMYDYTAQNDDELAFSKGQIINVLNKEDP--DWWKGELNGQVGLFPSNYV 52
PH_CNK_insect-like cd13326
Connector enhancer of KSR (Kinase suppressor of ras) (CNK) pleckstrin homology (PH) domain; ...
111-205 2.15e-06

Connector enhancer of KSR (Kinase suppressor of ras) (CNK) pleckstrin homology (PH) domain; CNK family members function as protein scaffolds, regulating the activity and the subcellular localization of RAS activated RAF. There is a single CNK protein present in Drosophila and Caenorhabditis elegans in contrast to mammals which have 3 CNK proteins (CNK1, CNK2, and CNK3). All of the CNK members contain a sterile a motif (SAM), a conserved region in CNK (CRIC) domain, and a PSD-95/DLG-1/ZO-1 (PDZ) domain, and a PH domain. A CNK2 splice variant CNK2A also has a PDZ domain-binding motif at its C terminus and Drosophila CNK (D-CNK) also has a domain known as the Raf-interacting region (RIR) that mediates binding of the Drosophila Raf kinase. This cd contains CNKs from insects, spiders, mollusks, and nematodes. PH domains have diverse functions, but in general are involved in targeting proteins to the appropriate cellular location or in the interaction with a binding partner. They share little sequence conservation, but all have a common fold, which is electrostatically polarized. Less than 10% of PH domains bind phosphoinositide phosphates (PIPs) with high affinity and specificity. PH domains are distinguished from other PIP-binding domains by their specific high-affinity binding to PIPs with two vicinal phosphate groups: PtdIns(3,4)P2, PtdIns(4,5)P2 or PtdIns(3,4,5)P3 which results in targeting some PH domain proteins to the plasma membrane. A few display strong specificity in lipid binding. Any specificity is usually determined by loop regions or insertions in the N-terminus of the domain, which are not conserved across all PH domains. PH domains are found in cellular signaling proteins such as serine/threonine kinase, tyrosine kinases, regulators of G-proteins, endocytotic GTPases, adaptors, as well as cytoskeletal associated molecules and in lipid associated enzymes.


Pssm-ID: 270135  Cd Length: 91  Bit Score: 45.41  E-value: 2.15e-06
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 115527076 111 QGYLEKKSKDHsFFGSEWQKRWCVVSRGLFYYYANEKSKQPKGTFLIKGYGVRMAPHLRrdSKKEScFEL--TSQdrrSY 188
Cdd:cd13326    2 QGWLYQRRRKG-KGGGKWAKRWFVLKGSNLYGFRSQESTKADCVIFLPGFTVSPAPEVK--SRKYA-FKVyhTGT---VF 74
                         90
                 ....*....|....*..
gi 115527076 189 EFTATSPAEARDWVDQI 205
Cdd:cd13326   75 YFAAESQEDMKKWLDLL 91
SH3_GRB2_like_N cd11804
N-terminal Src homology 3 domain of Growth factor receptor-bound protein 2 (GRB2) and related ...
300-349 2.20e-06

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


Pssm-ID: 212738 [Multi-domain]  Cd Length: 52  Bit Score: 44.27  E-value: 2.20e-06
                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|
gi 115527076 300 GLWDCHGDQPDELSFQRGDLIRILSKEYNMyGWWVGELNSLVGIVPKEYL 349
Cdd:cd11804    4 AKHDFKATAEDELSFKKGSILKVLNMEDDP-NWYKAELDGKEGLIPKNYI 52
SH3_CIN85_3 cd12057
Third Src Homology 3 domain (SH3C) of Cbl-interacting protein of 85 kDa; CIN85, also called ...
310-349 2.22e-06

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


Pssm-ID: 212990 [Multi-domain]  Cd Length: 56  Bit Score: 44.50  E-value: 2.22e-06
                         10        20        30        40
                 ....*....|....*....|....*....|....*....|
gi 115527076 310 DELSFQRGDLIRILSKEYNMYGWWVGELNSLVGIVPKEYL 349
Cdd:cd12057   14 DELTIKEGDIVTLISKDCIDAGWWEGELNGRRGVFPDNFV 53
SH3_Intersectin2_5 cd11996
Fifth Src homology 3 domain (or SH3E) of Intersectin-2; Intersectin-2 (ITSN2) is an adaptor ...
301-349 2.27e-06

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


Pssm-ID: 212929 [Multi-domain]  Cd Length: 54  Bit Score: 44.20  E-value: 2.27e-06
                         10        20        30        40
                 ....*....|....*....|....*....|....*....|....*....
gi 115527076 301 LWDCHGDQPDELSFQRGDLIRILSKEYNmyGWWVGELNSLVGIVPKEYL 349
Cdd:cd11996    6 MYDYTANNEDELSFSKGQLINVLNKDDP--DWWQGEINGVTGLFPSNYV 52
SH3_Abi cd11826
Src homology 3 domain of Abl Interactor proteins; Abl interactor (Abi) proteins are adaptor ...
301-350 2.29e-06

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


Pssm-ID: 212760 [Multi-domain]  Cd Length: 52  Bit Score: 44.23  E-value: 2.29e-06
                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|
gi 115527076 301 LWDCHGDQPDELSFQRGDLIRILSKeyNMYGWWVGELNSLVGIVPKEYLT 350
Cdd:cd11826    5 LYDYTADKDDELSFQEGDIIYVTKK--NDDGWYEGVLNGVTGLFPGNYVE 52
SH3_Nck1_3 cd11904
Third Src Homology 3 domain of Nck1 adaptor protein; Nck1 (also called Nckalpha) plays a ...
299-350 2.53e-06

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


Pssm-ID: 212837 [Multi-domain]  Cd Length: 57  Bit Score: 44.25  E-value: 2.53e-06
                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|...
gi 115527076 299 QGLWDCHGDQPDELSFQRGDLIRILSKEYNMYGWW-VGELNSLVGIVPKEYLT 350
Cdd:cd11904    4 QALYPFSSSNDEELNFEKGEVMDVIEKPENDPEWWkCRKANGQVGLVPKNYVT 56
SH3_SH3TC cd11885
Src Homology 3 domain of SH3 domain and tetratricopeptide repeat-containing (SH3TC) proteins ...
301-348 2.75e-06

Src Homology 3 domain of SH3 domain and tetratricopeptide repeat-containing (SH3TC) proteins and similar domains; This subfamily is composed of vertebrate SH3TC proteins and hypothetical fungal proteins containing BAR and SH3 domains. Mammals contain two SH3TC proteins, SH3TC1 and SH3TC2. The function of SH3TC1 is unknown. SH3TC2 is localized in Schwann cells in the peripheral nervous system, where it interacts with Rab11 and plays a role in peripheral nerve myelination. Mutations in SH3TC2 are associated with Charcot-Marie-Tooth disease type 4C, a severe hereditary peripheral neuropathy with symptoms that include progressive scoliosis, delayed age of walking, muscular atrophy, distal weakness, and reduced nerve conduction velocity. SH3 domains bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs; they play a role in the regulation of enzymes by intramolecular interactions, changing the subcellular localization of signal pathway components and mediate multiprotein complex assemblies.


Pssm-ID: 212818  Cd Length: 55  Bit Score: 44.23  E-value: 2.75e-06
                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|
gi 115527076 301 LWDCHGDQPDELSFQRGDLIRILSKEYNMYGWWVG--ELNSLVGIVPKEY 348
Cdd:cd11885    5 KMDFEGVEPGELSFRQGDSIEIIGDLIPGLQWFVGrsKSSGRVGFVPTNH 54
PH2_ADAP cd01251
ArfGAP with dual PH domains Pleckstrin homology (PH) domain, repeat 2; ADAP (also called ...
107-205 3.09e-06

ArfGAP with dual PH domains Pleckstrin homology (PH) domain, repeat 2; ADAP (also called centaurin alpha) is a phophatidlyinositide binding protein consisting of an N-terminal ArfGAP domain and two PH domains. In response to growth factor activation, PI3K phosphorylates phosphatidylinositol 4,5-bisphosphate to phosphatidylinositol 3,4,5-trisphosphate. Centaurin alpha 1 is recruited to the plasma membrane following growth factor stimulation by specific binding of its PH domain to phosphatidylinositol 3,4,5-trisphosphate. Centaurin alpha 2 is constitutively bound to the plasma membrane since it binds phosphatidylinositol 4,5-bisphosphate and phosphatidylinositol 3,4,5-trisphosphate with equal affinity. This cd contains the second PH domain repeat. PH domains have diverse functions, but in general are involved in targeting proteins to the appropriate cellular location or in the interaction with a binding partner. They share little sequence conservation, but all have a common fold, which is electrostatically polarized. Less than 10% of PH domains bind phosphoinositide phosphates (PIPs) with high affinity and specificity. PH domains are distinguished from other PIP-binding domains by their specific high-affinity binding to PIPs with two vicinal phosphate groups: PtdIns(3,4)P2, PtdIns(4,5)P2 or PtdIns(3,4,5)P3 which results in targeting some PH domain proteins to the plasma membrane. A few display strong specificity in lipid binding. Any specificity is usually determined by loop regions or insertions in the N-terminus of the domain, which are not conserved across all PH domains. PH domains are found in cellular signaling proteins such as serine/threonine kinase, tyrosine kinases, regulators of G-proteins, endocytotic GTPases, adaptors, as well as cytoskeletal associated molecules and in lipid associated enzymes.


Pssm-ID: 241282  Cd Length: 105  Bit Score: 45.27  E-value: 3.09e-06
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 115527076 107 NVIKQGYLEK---KSKDhsffgsEWQKRWCVVSRGLFYYYANEKSKQPKGTFLI----KGYGVRM-APHLRRDsKKESCF 178
Cdd:cd01251    1 DFLKEGYLEKtgpKQTD------GFRKRWFTLDDRRLMYFKDPLDAFPKGEIFIgskeEGYSVREgLPPGIKG-HWGFGF 73
                         90       100
                 ....*....|....*....|....*..
gi 115527076 179 ELTSQDrRSYEFTATSPAEARDWVDQI 205
Cdd:cd01251   74 TLVTPD-RTFLLSAETEEERREWITAI 99
SH3_p67phox_C cd12046
C-terminal (or second) Src Homology 3 domain of the p67phox subunit of NADPH oxidase; p67phox, ...
297-350 3.61e-06

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


Pssm-ID: 212979 [Multi-domain]  Cd Length: 53  Bit Score: 43.64  E-value: 3.61e-06
                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|....
gi 115527076 297 YYQGLWDCHGDQPDELSFQRGDLIRILSKEYNmyGWWVGELNSLVGIVPKEYLT 350
Cdd:cd12046    1 QVVALFSYEASQPEDLEFQKGDVILVLSKVNE--DWLEGQCKGKIGIFPSAFVE 52
PH_Cla4_Ste20 cd13279
Pleckstrin homology (PH) domain; Budding yeast contain two main p21-activated kinases (PAKs), ...
108-205 3.79e-06

Pleckstrin homology (PH) domain; Budding yeast contain two main p21-activated kinases (PAKs), Cla4 and Ste20. The yeast Ste20 protein kinase is involved in pheromone response, though the function of Ste20 mammalian homologs is unknown. Cla4 is involved in budding and cytokinesis and interacts with Cdc42, a GTPase required for polarized cell growth as is Pak. Cla4 and Ste20 kinases share a function in localizing cell growth with respect to the septin ring. They both contain a PH domain, a Cdc42/Rac interactive binding (CRIB) domain, and a C-terminal Protein Kinase catalytic (PKc) domain. PH domains have diverse functions, but in general are involved in targeting proteins to the appropriate cellular location or in the interaction with a binding partner. They share little sequence conservation, but all have a common fold, which is electrostatically polarized. Less than 10% of PH domains bind phosphoinositide phosphates (PIPs) with high affinity and specificity. PH domains are distinguished from other PIP-binding domains by their specific high-affinity binding to PIPs with two vicinal phosphate groups: PtdIns(3,4)P2, PtdIns(4,5)P2 or PtdIns(3,4,5)P3 which results in targeting some PH domain proteins to the plasma membrane. A few display strong specificity in lipid binding. Any specificity is usually determined by loop regions or insertions in the N-terminus of the domain, which are not conserved across all PH domains. PH domains are found in cellular signaling proteins such as serine/threonine kinase, tyrosine kinases, regulators of G-proteins, endocytotic GTPases, adaptors, as well as cytoskeletal associated molecules and in lipid associated enzymes.


Pssm-ID: 270097  Cd Length: 92  Bit Score: 44.54  E-value: 3.79e-06
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 115527076 108 VIKQGYLekKSKDHSFFGSEWQKRWCVVSRGLFYYYANEKSKQPKGTFLIKgygvrMAPHLRRDSKKESCFEL-TSQDRR 186
Cdd:cd13279    1 VVKSGWV--SVKEDGLLSFRWSKRYLVLREQSLDFYKNESSSSASLSIPLK-----DISNVSRTDLKPYCFEIvRKSSTK 73
                         90
                 ....*....|....*....
gi 115527076 187 SYEFTATSPAEARDWVDQI 205
Cdd:cd13279   74 SIYISVKSDDELYDWMDDI 92
SH3_ASPP1 cd11954
Src Homology 3 domain of Apoptosis Stimulating of p53 protein 1; ASPP1, like ASPP2, activates ...
301-349 4.04e-06

Src Homology 3 domain of Apoptosis Stimulating of p53 protein 1; ASPP1, like ASPP2, activates the apoptotic function of the p53 family of tumor suppressors (p53, p63, and p73). In addition, it functions in the cytoplasm to regulate the nuclear localization of the transcriptional cofactors YAP and TAZ by inihibiting their phosphorylation; YAP and TAZ are important regulators of cell expansion, differentiation, migration, and invasion. ASPP1 is downregulated in breast tumors expressing wild-type p53. It contains a proline-rich region, four ankyrin (ANK) repeats, and an SH3 domain at its C-terminal half. The SH3 domain and the ANK repeats of ASPP1 contribute to the p53 binding site; they bind to the DNA binding domain of p53. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 212887 [Multi-domain]  Cd Length: 57  Bit Score: 43.86  E-value: 4.04e-06
                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|
gi 115527076 301 LWDCHGDQPDELSFQRGDLIRILS-KEYNMYGWWVGELNSLVGIVPKEYL 349
Cdd:cd11954    6 LWDYEAQNADELSFQEGDAITILRrKDDSETEWWWARLNDKEGYVPKNLL 55
SH3_FCHSD1_2 cd11895
Second Src Homology 3 domain of FCH and double SH3 domains protein 1; FCHSD1 has a domain ...
299-345 5.02e-06

Second Src Homology 3 domain of FCH and double SH3 domains protein 1; FCHSD1 has a domain structure consisting of an N-terminal F-BAR (FES-CIP4 Homology and Bin/Amphiphysin/Rvs), two SH3, and C-terminal proline-rich domains. It has only been characterized in silico and its function is unknown. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 212828  Cd Length: 58  Bit Score: 43.42  E-value: 5.02e-06
                         10        20        30        40
                 ....*....|....*....|....*....|....*....|....*....
gi 115527076 299 QGLWDCHGDQPDELSFQRGDLIRILSKEYNMY--GWWVGELNSLVGIVP 345
Cdd:cd11895    3 RALYSYTGQSPEELSFPEGALIRLLPRAQDGVddGFWRGEFGGRVGVFP 51
SH3_GRAP2_N cd11947
N-terminal Src homology 3 domain of GRB2-related adaptor protein 2; GRAP2 is also called GADS ...
299-349 6.45e-06

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


Pssm-ID: 212880 [Multi-domain]  Cd Length: 52  Bit Score: 42.86  E-value: 6.45e-06
                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|.
gi 115527076 299 QGLWDCHGDQPDELSFQRGDLIRILSKEYNmygWWVGELNSLVGIVPKEYL 349
Cdd:cd11947    3 RGKFDFTASGEDELSFKKGDVLKILSSDDI---WFKAELNGEEGYVPKNFV 50
SH3_BCAR1 cd12001
Src homology 3 domain of the CAS (Crk-Associated Substrate) scaffolding protein family member, ...
299-349 7.18e-06

Src homology 3 domain of the CAS (Crk-Associated Substrate) scaffolding protein family member, Breast Cancer Anti-estrogen Resistance 1; BCAR1, also called p130cas or CASS1, is the founding member of the CAS family of scaffolding proteins and was originally identified through its ability to associate with Crk. The name BCAR1 was designated because the human gene was identified in a screen for genes that promote resistance to tamoxifen. It is widely expressed and its deletion is lethal in mice. It plays a role in regulating cell motility, survival, proliferation, transformation, cancer progression, and bacterial pathogenesis. CAS proteins function as molecular scaffolds to regulate protein complexes that are involved in many cellular processes. They share a common domain structure that includes an N-terminal SH3 domain, an unstructured substrate domain that contains many YxxP motifs, a serine-rich four-helix bundle, and a FAT-like C-terminal domain. The SH3 domain of CAS proteins binds to diverse partners including FAK, FRNK, Pyk2, PTP-PEST, DOCK180, among others. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 212934  Cd Length: 68  Bit Score: 43.49  E-value: 7.18e-06
                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|..
gi 115527076 299 QGLWDCHGDQPDELSFQRGDLIRILSKEYN-MYGWWVGELNSLVGIVPKEYL 349
Cdd:cd12001    6 KALYDNVAESPDELSFRKGDIMTVLERDTQgLDGWWLCSLHGRQGIVPGNRL 57
PH_RhoGAP2 cd13378
Rho GTPase activating protein 2 Pleckstrin homology (PH) domain; RhoGAP2 (also called RhoGap22 ...
108-205 7.25e-06

Rho GTPase activating protein 2 Pleckstrin homology (PH) domain; RhoGAP2 (also called RhoGap22 or ArhGap22) are involved in cell polarity, cell morphology and cytoskeletal organization. They activate a GTPase belonging to the RAS superfamily of small GTP-binding proteins. The encoded protein is insulin-responsive, is dependent on the kinase Akt, and requires the Akt-dependent 14-3-3 binding protein which binds sequentially to two serine residues resulting in regulation of cell motility. Members here contain an N-terminal PH domain followed by a RhoGAP domain and either a BAR or TATA Binding Protein (TBP) Associated Factor 4 (TAF4) domain. PH domains have diverse functions, but in general are involved in targeting proteins to the appropriate cellular location or in the interaction with a binding partner. They share little sequence conservation, but all have a common fold, which is electrostatically polarized. Less than 10% of PH domains bind phosphoinositide phosphates (PIPs) with high affinity and specificity. PH domains are distinguished from other PIP-binding domains by their specific high-affinity binding to PIPs with two vicinal phosphate groups: PtdIns(3,4)P2, PtdIns(4,5)P2 or PtdIns(3,4,5)P3 which results in targeting some PH domain proteins to the plasma membrane. A few display strong specificity in lipid binding. Any specificity is usually determined by loop regions or insertions in the N-terminus of the domain, which are not conserved across all PH domains. PH domains are found in cellular signaling proteins such as serine/threonine kinase, tyrosine kinases, regulators of G-proteins, endocytotic GTPases, adaptors, as well as cytoskeletal associated molecules and in lipid associated enzymes.


Pssm-ID: 241529  Cd Length: 116  Bit Score: 44.55  E-value: 7.25e-06
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 115527076 108 VIKQGYLEKKSKdhsfFGSEWQKRWCVVSRGLFYYYANEKSKQPKGTFLIKGYGVRMAPHLRRDSKKEsCFELT---SQD 184
Cdd:cd13378    3 VLKAGWLKKQRS----IMKNWQQRWFVLRGDQLFYYKDEEETKPQGCISLQGSQVNELPPNPEEPGKH-LFEILpggAGD 77
                         90       100
                 ....*....|....*....|....*...
gi 115527076 185 R-------RSYEFTATSPAEARDWVDQI 205
Cdd:cd13378   78 RekvpmnhEAFLLMANSQSDMEDWVKAI 105
SH3_ASAP cd11821
Src homology 3 domain of ArfGAP with SH3 domain, ankyrin repeat and PH domain containing ...
299-337 8.62e-06

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


Pssm-ID: 212755 [Multi-domain]  Cd Length: 53  Bit Score: 42.69  E-value: 8.62e-06
                         10        20        30
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gi 115527076 299 QGLWDCHGDQPDELSFQRGDLIRILSKEYNmyGWWVGEL 337
Cdd:cd11821    3 RALYDCQADNDDELTFSEGEIIVVTGEEDD--EWWEGHI 39
PH_TAAP2-like cd13255
Tandem PH-domain-containing protein 2 Pleckstrin homology (PH) domain; The binding of TAPP2 ...
106-205 9.74e-06

Tandem PH-domain-containing protein 2 Pleckstrin homology (PH) domain; The binding of TAPP2 (also called PLEKHA2) adaptors to PtdIns(3,4)P(2), but not PI(3,4, 5)P3, function as negative regulators of insulin and PI3K signalling pathways (i.e. TAPP/utrophin/syntrophin complex). TAPP2 contains two sequential PH domains in which the C-terminal PH domain specifically binds PtdIns(3,4)P2 with high affinity. The N-terminal PH domain does not interact with any phosphoinositide tested. They also contain a C-terminal PDZ-binding motif that interacts with several PDZ-binding proteins, including PTPN13 (known previously as PTPL1 or FAP-1) as well as the scaffolding proteins MUPP1 (multiple PDZ-domain-containing protein 1), syntrophin and utrophin. The members here are most sequence similar to TAPP2 proteins, but may not be actual TAPP2 proteins. PH domains have diverse functions, but in general are involved in targeting proteins to the appropriate cellular location or in the interaction with a binding partner. They share little sequence conservation, but all have a common fold, which is electrostatically polarized. Less than 10% of PH domains bind phosphoinositide phosphates (PIPs) with high affinity and specificity. PH domains are distinguished from other PIP-binding domains by their specific high-affinity binding to PIPs with two vicinal phosphate groups: PtdIns(3,4)P2, PtdIns(4,5)P2 or PtdIns(3,4,5)P3 which results in targeting some PH domain proteins to the plasma membrane. A few display strong specificity in lipid binding. Any specificity is usually determined by loop regions or insertions in the N-terminus of the domain, which are not conserved across all PH domains. PH domains are found in cellular signaling proteins such as serine/threonine kinase, tyrosine kinases, regulators of G-proteins, endocytotic GTPases, adaptors, as well as cytoskeletal associated molecules and in lipid associated enzymes.


Pssm-ID: 270075  Cd Length: 110  Bit Score: 43.94  E-value: 9.74e-06
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 115527076 106 DNVIKQGYLEKKSKDHSffgsEWQKRWCVVSRGLFYYYANEKSKQPkgtflikgygVRMAP----------HLRrdsKKE 175
Cdd:cd13255    4 EAVLKAGYLEKKGERRK----TWKKRWFVLRPTKLAYYKNDKEYRL----------LRLIDltdihtctevQLK---KHD 66
                         90       100       110
                 ....*....|....*....|....*....|
gi 115527076 176 SCFELTSQDRRSYeFTATSPAEARDWVDQI 205
Cdd:cd13255   67 NTFGIVTPARTFY-VQADSKAEMESWISAI 95
SH3_Nck_3 cd11767
Third Src Homology 3 domain of Nck adaptor proteins; This group contains the third SH3 domain ...
299-350 1.13e-05

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


Pssm-ID: 212701 [Multi-domain]  Cd Length: 56  Bit Score: 42.30  E-value: 1.13e-05
                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|...
gi 115527076 299 QGLWDCHGDQPDELSFQRGDLIRILSKEYNMYGWWVGE-LNSLVGIVPKEYLT 350
Cdd:cd11767    3 VALYPFTGENDEELSFEKGERLEIIEKPEDDPDWWKARnALGTTGLVPRNYVE 55
SH3_srGAP cd11809
Src homology 3 domain of Slit-Robo GTPase Activating Proteins; Slit-Robo GTPase Activating ...
306-350 1.29e-05

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


Pssm-ID: 212743 [Multi-domain]  Cd Length: 53  Bit Score: 42.00  E-value: 1.29e-05
                         10        20        30        40
                 ....*....|....*....|....*....|....*....|....*
gi 115527076 306 GDQPDELSFQRGDLIRILSKEYNmyGWWVGELNSLVGIVPKEYLT 350
Cdd:cd11809   10 GRSERELSFKKGDSLTLYRQVSD--DWWRGQLNGQDGLVPHKYIT 52
SH3_GRAP_C cd11951
C-terminal Src homology 3 domain of GRB2-related adaptor protein; GRAP is a GRB-2 like adaptor ...
297-349 1.43e-05

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


Pssm-ID: 212884  Cd Length: 53  Bit Score: 42.09  E-value: 1.43e-05
                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|....
gi 115527076 297 YYQGLWDCHGDQPDELSFQRGDLIRIL-SKEYNmygWWVGELNSLVGIVPKEYL 349
Cdd:cd11951    1 FVQAQYDFSAEDPSQLSFRRGDIIEVLdCPDPN---WWRGRISGRVGFFPRNYV 51
SH3_Pex13p_fungal cd11771
Src Homology 3 domain of fungal peroxisomal membrane protein Pex13p; Pex13p, located in the ...
301-350 1.48e-05

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


Pssm-ID: 212705 [Multi-domain]  Cd Length: 60  Bit Score: 42.26  E-value: 1.48e-05
                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|....*
gi 115527076 301 LWDCHGDQPD-ELSFQRGDLIRILSK---EYNMYGWWVGEL-NSLVGIVPKEYLT 350
Cdd:cd11771    5 LYDFTPENPEmELSLKKGDIVAVLSKtdpLGRDSEWWKGRTrDGRIGWFPSNYVE 59
PH_RhoGap24 cd13379
Rho GTPase activating protein 24 Pleckstrin homology (PH) domain; RhoGap24 (also called ...
107-205 1.75e-05

Rho GTPase activating protein 24 Pleckstrin homology (PH) domain; RhoGap24 (also called ARHGAP24, p73RhoGAp, and Filamin-A-associated RhoGAP) like other RhoGAPs are involved in cell polarity, cell morphology and cytoskeletal organization. They act as GTPase activators for the Rac-type GTPases by converting them to an inactive GDP-bound state and control actin remodeling by inactivating Rac downstream of Rho leading to suppress leading edge protrusion and promotes cell retraction to achieve cellular polarity and are able to suppress RAC1 and CDC42 activity in vitro. Overexpression of these proteins induces cell rounding with partial or complete disruption of actin stress fibers and formation of membrane ruffles, lamellipodia, and filopodia. Members here contain an N-terminal PH domain followed by a RhoGAP domain and either a BAR or TATA Binding Protein (TBP) Associated Factor 4 (TAF4) domain. PH domains have diverse functions, but in general are involved in targeting proteins to the appropriate cellular location or in the interaction with a binding partner. They share little sequence conservation, but all have a common fold, which is electrostatically polarized. Less than 10% of PH domains bind phosphoinositide phosphates (PIPs) with high affinity and specificity. PH domains are distinguished from other PIP-binding domains by their specific high-affinity binding to PIPs with two vicinal phosphate groups: PtdIns(3,4)P2, PtdIns(4,5)P2 or PtdIns(3,4,5)P3 which results in targeting some PH domain proteins to the plasma membrane. A few display strong specificity in lipid binding. Any specificity is usually determined by loop regions or insertions in the N-terminus of the domain, which are not conserved across all PH domains. PH domains are found in cellular signaling proteins such as serine/threonine kinase, tyrosine kinases, regulators of G-proteins, endocytotic GTPases, adaptors, as well as cytoskeletal associated molecules and in lipid associated enzymes.


Pssm-ID: 241530  Cd Length: 114  Bit Score: 43.42  E-value: 1.75e-05
                         10        20        30        40        50        60        70        80
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gi 115527076 107 NVIKQGYLEKKSKdhsfFGSEWQKRWCVVSRGLFYYYANEKSKQPKGTFLIKGYGVRMAPhLRRDSKKESCFELT----- 181
Cdd:cd13379    2 EVIKCGWLRKQGG----FVKTWHTRWFVLKGDQLYYFKDEDETKPLGTIFLPGNRVTEHP-CNEEEPGKFLFEVVpggdr 76
                         90       100
                 ....*....|....*....|....*..
gi 115527076 182 ---SQDRRSYEFTATSPAEARDWVDQI 205
Cdd:cd13379   77 ermTANHETYLLMASTQNDMEDWVKSI 103
SH3_ASPP2 cd11953
Src Homology 3 (SH3) domain of Apoptosis Stimulating of p53 protein 2; ASPP2 is the full ...
301-349 1.81e-05

Src Homology 3 (SH3) domain of Apoptosis Stimulating of p53 protein 2; ASPP2 is the full length form of the previously-identified tumor supressor, p53-binding protein 2 (p53BP2). ASPP2 activates the apoptotic function of the p53 family of tumor suppressors (p53, p63, and p73). It plays a central role in regulating apoptosis and cell growth; ASPP2-deficient mice show postnatal death. Downregulated expression of ASPP2 is frequently found in breast tumors, lung cancer, and diffuse large B-cell lymphoma where it is correlated with a poor clinical outcome. ASPP2 contains a proline-rich region, four ankyrin (ANK) repeats, and an SH3 domain at its C-terminal half. The SH3 domain and the ANK repeats of ASPP2 contribute to the p53 binding site; they bind to the DNA binding domain of p53. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 212886 [Multi-domain]  Cd Length: 57  Bit Score: 41.86  E-value: 1.81e-05
                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|
gi 115527076 301 LWDCHGDQPDELSFQRGDLIRILSKE-YNMYGWWVGELNSLVGIVPKEYL 349
Cdd:cd11953    6 LWDYEGESDDELSFKEGDCMTILRREdEDETEWWWARLNDKEGYVPRNLL 55
SH3_GRAP_N cd11948
N-terminal Src homology 3 domain of GRB2-related adaptor protein; GRAP is a GRB-2 like adaptor ...
301-349 2.21e-05

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


Pssm-ID: 212881 [Multi-domain]  Cd Length: 54  Bit Score: 41.34  E-value: 2.21e-05
                         10        20        30        40
                 ....*....|....*....|....*....|....*....|....*....
gi 115527076 301 LWDCHGDQPDELSFQRGDLIRILSKEYNMyGWWVGELNSLVGIVPKEYL 349
Cdd:cd11948    5 LYSFQATESDELPFQKGDILKILNMEDDQ-NWYKAELQGREGYIPKNYI 52
SH3_VAV1_2 cd11976
C-terminal (or second) Src homology 3 domain of VAV1 protein; VAV1 is expressed predominantly ...
311-349 3.79e-05

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


Pssm-ID: 212909 [Multi-domain]  Cd Length: 54  Bit Score: 40.70  E-value: 3.79e-05
                         10        20        30
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gi 115527076 311 ELSFQRGDLIRILSKEyNMYGWWVGELNSLVGIVPKEYL 349
Cdd:cd11976   15 ELSLKEGDIIKILNKK-GQQGWWRGEIYGRVGWFPANYV 52
SH3_PACSIN cd11843
Src homology 3 domain of Protein kinase C and Casein kinase Substrate in Neurons (PACSIN) ...
301-348 4.39e-05

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: 40.48  E-value: 4.39e-05
                         10        20        30        40
                 ....*....|....*....|....*....|....*....|....*...
gi 115527076 301 LWDCHGDQPDELSFQRGDLIRILSKEyNMYGWWVGELNSLVGIVPKEY 348
Cdd:cd11843    5 LYDYEGQESDELSFKAGDILTKLEEE-DEQGWCKGRLDGRVGLYPANY 51
SH3_Sorbs_1 cd11781
First Src Homology 3 domain of Sorbin and SH3 domain containing (Sorbs) proteins and similar ...
300-348 4.59e-05

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


Pssm-ID: 212715 [Multi-domain]  Cd Length: 53  Bit Score: 40.40  E-value: 4.59e-05
                         10        20        30        40
                 ....*....|....*....|....*....|....*....|....*....
gi 115527076 300 GLWDCHGDQPDELSFQRGDLIRILsKEYNMYgWWVGELNSLVGIVPKEY 348
Cdd:cd11781    4 ALYPFKAQSAKELSLKKGDIIYIR-RQIDKN-WYEGEHNGRVGIFPASY 50
SH3_Brk cd11847
Src homology 3 domain of Brk (Breast tumor kinase) Protein Tyrosine Kinase (PTK), also called ...
298-349 4.96e-05

Src homology 3 domain of Brk (Breast tumor kinase) Protein Tyrosine Kinase (PTK), also called PTK6; Brk is a cytoplasmic (or non-receptor) PTK with limited homology to Src kinases. It has been found to be overexpressed in a majority of breast tumors. It plays roles in normal cell differentiation, proliferation, survival, migration, and cell cycle progression. Brk substrates include RNA-binding proteins (SLM-1/2, Sam68), transcription factors (STAT3/5), and signaling molecules (Akt, paxillin, IRS-4). Src kinases in general contain an N-terminal SH4 domain with a myristoylation site, followed by SH3 and SH2 domains, a tyr kinase domain, and a regulatory C-terminal region containing a conserved tyr; they are activated by autophosphorylation at the tyr kinase domain, but are negatively regulated by phosphorylation at the C-terminal tyr by Csk (C-terminal Src Kinase). However, Brk lacks the N-terminal myristoylation site. The SH3 domain of Src kinases contributes to substrate recruitment by binding adaptor proteins/substrates, and regulation of kinase activity through an intramolecular interaction. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 212781 [Multi-domain]  Cd Length: 58  Bit Score: 40.62  E-value: 4.96e-05
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                 ....*....|....*....|....*....|....*....|....*....|....*...
gi 115527076 298 YQGLWDCHGDQPDELSFQRGDLIRILSKEYNmygWW----VGELNSLV--GIVPKEYL 349
Cdd:cd11847    2 YKALWDFKARGDEELSFQAGDQFRIAERSGD---WWtalkLDRAGGVVaqGFVPNNYL 56
SH3_VAV_2 cd11830
C-terminal (or second) Src homology 3 domain of VAV proteins; VAV proteins function both as ...
311-349 5.93e-05

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


Pssm-ID: 212764 [Multi-domain]  Cd Length: 54  Bit Score: 40.31  E-value: 5.93e-05
                         10        20        30
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gi 115527076 311 ELSFQRGDLIRILSKEyNMYGWWVGELNSLVGIVPKEYL 349
Cdd:cd11830   15 ELSLKEGDVVKIYNKK-GQQGWWRGEINGRIGWFPSTYV 52
SH3_CD2AP-like_1 cd11873
First Src Homology 3 domain (SH3A) of CD2-associated protein and similar proteins; This ...
301-345 6.06e-05

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: 40.33  E-value: 6.06e-05
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gi 115527076 301 LWDCHGDQPDELSFQRGDLIRILSKEYNmyGWWVGELNSLVGIVP 345
Cdd:cd11873    5 EFDYDAEEPDELTLKVGDIITNVKKMEE--GWWEGTLNGKRGMFP 47
SH3_Eve1_5 cd11818
Fifth Src homology 3 domain of ADAM-binding protein Eve-1; Eve-1, also called SH3 ...
299-348 6.15e-05

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


Pssm-ID: 212752 [Multi-domain]  Cd Length: 50  Bit Score: 40.16  E-value: 6.15e-05
                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|
gi 115527076 299 QGLWDCHGDQPDELSFQRGDLIRILskEYNMYGWWVGELNSLVGIVPKEY 348
Cdd:cd11818    3 RALYDFTGENEDELSFKAGDIITEL--ESIDEEWMSGELRGKSGIFPKNF 50
PH_RASA1 cd13260
RAS p21 protein activator (GTPase activating protein) 1 Pleckstrin homology (PH) domain; RASA1 ...
107-203 6.47e-05

RAS p21 protein activator (GTPase activating protein) 1 Pleckstrin homology (PH) domain; RASA1 (also called RasGap1 or p120) is a member of the RasGAP family of GTPase-activating proteins. RASA1 contains N-terminal SH2-SH3-SH2 domains, followed by two C2 domains, a PH domain, a RasGAP domain, and a BTK domain. Splice variants lack the N-terminal domains. It is a cytosolic vertebrate protein that acts as a suppressor of RAS via its C-terminal GAP domain function, enhancing the weak intrinsic GTPase activity of RAS proteins resulting in the inactive GDP-bound form of RAS, allowing control of cellular proliferation and differentiation. Additionally, it is involved in mitogenic signal transmission towards downstream interacting partners through its N-terminal SH2-SH3-SH2 domains. RASA1 interacts with a number of proteins including: G3BP1, SOCS3, ANXA6, Huntingtin, KHDRBS1, Src, EPHB3, EPH receptor B2, Insulin-like growth factor 1 receptor, PTK2B, DOK1, PDGFRB, HCK, Caveolin 2, DNAJA3, HRAS, GNB2L1 and NCK1. PH domains have diverse functions, but in general are involved in targeting proteins to the appropriate cellular location or in the interaction with a binding partner. They share little sequence conservation, but all have a common fold, which is electrostatically polarized. Less than 10% of PH domains bind phosphoinositide phosphates (PIPs) with high affinity and specificity. PH domains are distinguished from other PIP-binding domains by their specific high-affinity binding to PIPs with two vicinal phosphate groups: PtdIns(3,4)P2, PtdIns(4,5)P2 or PtdIns(3,4,5)P3 which results in targeting some PH domain proteins to the plasma membrane. A few display strong specificity in lipid binding. Any specificity is usually determined by loop regions or insertions in the N-terminus of the domain, which are not conserved across all PH domains. PH domains are found in cellular signaling proteins such as serine/threonine kinase, tyrosine kinases, regulators of G-proteins, endocytotic GTPases, adaptors, as well as cytoskeletal associated molecules and in lipid associated enzymes.


Pssm-ID: 270080  Cd Length: 103  Bit Score: 41.56  E-value: 6.47e-05
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 115527076 107 NVIKQGYLEKKSKDHSffgsEWQKRWCVV--SRGLFYYYANEKSKQPKGTFLIKGYGVrmapHLRRDS--KKESCFELTS 182
Cdd:cd13260    2 GIDKKGYLLKKGGKNK----KWKNLYFVLegKEQHLYFFDNEKRTKPKGLIDLSYCSL----YPVHDSlfGRPNCFQIVV 73
                         90       100
                 ....*....|....*....|....
gi 115527076 183 Q---DRRSYEFTATSPAEARDWVD 203
Cdd:cd13260   74 RalnESTITYLCADTAELAQEWMR 97
SH3_NEDD9 cd12002
Src homology 3 domain of CAS (Crk-Associated Substrate) scaffolding protein family member, ...
299-345 7.07e-05

Src homology 3 domain of CAS (Crk-Associated Substrate) scaffolding protein family member, Neural precursor cell Expressed, Developmentally Down-regulated 9; NEDD9 is also called human enhancer of filamentation 1 (HEF1) or CAS-L (Crk-associated substrate in lymphocyte). It was first described as a gene predominantly expressed in early embryonic brain, and was also isolated from a screen of human proteins that regulate filamentous budding in yeast, and as a tyrosine phosphorylated protein in lymphocytes. It promotes metastasis in different solid tumors. NEDD9 localizes in focal adhesions and associates with FAK and Abl kinase. It also interacts with SMAD3 and the proteasomal machinery which allows its rapid turnover; these interactions are not shared by other CAS proteins. CAS proteins function as molecular scaffolds to regulate protein complexes that are involved in many cellular processes. They share a common domain structure that includes an N-terminal SH3 domain, an unstructured substrate domain that contains many YxxP motifs, a serine-rich four-helix bundle, and a FAT-like C-terminal domain. The SH3 domain of CAS proteins binds to diverse partners including FAK, FRNK, Pyk2, PTP-PEST, DOCK180, among others. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 212935  Cd Length: 57  Bit Score: 40.35  E-value: 7.07e-05
                         10        20        30        40
                 ....*....|....*....|....*....|....*....|....*...
gi 115527076 299 QGLWDCHGDQPDELSFQRGDLIRILSKEYN-MYGWWVGELNSLVGIVP 345
Cdd:cd12002    3 RALYDNVPECAEELAFRKGDILTVIEQNTGgLEGWWLCSLHGRQGIAP 50
SH3_Intersectin_3 cd11838
Third Src homology 3 domain (or SH3C) of Intersectin; Intersectins (ITSNs) are adaptor ...
297-350 7.32e-05

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


Pssm-ID: 212772 [Multi-domain]  Cd Length: 52  Bit Score: 40.09  E-value: 7.32e-05
                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|....
gi 115527076 297 YYQGLWDCHGDQPDELSFQRGDLIRILSKEYNmygWWVGELNSLVGIVPKEYLT 350
Cdd:cd11838    1 EYIALYPYESNEPGDLTFNAGDVILVTKKDGE---WWTGTIGDRTGIFPSNYVR 51
SH3_ASPP cd11807
Src homology 3 domain of Apoptosis Stimulating of p53 proteins (ASPP); The ASPP family of ...
300-349 8.04e-05

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


Pssm-ID: 212741 [Multi-domain]  Cd Length: 57  Bit Score: 40.05  E-value: 8.04e-05
                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|.
gi 115527076 300 GLWDCHGDQPDELSFQRGDLIRILSKEYNM-YGWWVGELNSLVGIVPKEYL 349
Cdd:cd11807    5 ALFDYEAENGDELSFREGDELTVLRKGDDDeTEWWWARLNDKEGYVPRNLL 55
SH3_PIX cd11877
Src Homology 3 domain of Pak Interactive eXchange factors; PIX proteins are Rho guanine ...
298-350 8.19e-05

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: 39.99  E-value: 8.19e-05
                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|...
gi 115527076 298 YQGLWDCHGDQPDELSFQRGDLIRILSKEYNmyGWWVGELNSLVGIVPKEYLT 350
Cdd:cd11877    2 VRAKFNFEGTNEDELSFDKGDIITVTQVVEG--GWWEGTLNGKTGWFPSNYVK 52
SH3_Sdc25 cd11883
Src Homology 3 domain of Sdc25/Cdc25 guanine nucleotide exchange factors; This subfamily is ...
301-344 9.05e-05

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


Pssm-ID: 212816  Cd Length: 55  Bit Score: 39.57  E-value: 9.05e-05
                         10        20        30        40
                 ....*....|....*....|....*....|....*....|....
gi 115527076 301 LWDCHGDQPDELSFQRGDLIRILSKEYNmyGWWVGELNSLVGIV 344
Cdd:cd11883    5 LYDFTPKSKNQLSFKAGDIIYVLNKDPS--GWWDGVIISSSGKV 46
PH_SIP3 cd13280
Snf1p-interacting protein 3 Pleckstrin homology (PH) domain; SIP3 interacts with SNF1 protein ...
110-202 9.59e-05

Snf1p-interacting protein 3 Pleckstrin homology (PH) domain; SIP3 interacts with SNF1 protein kinase and activates transcription when anchored to DNA. It may function in the SNF1 pathway. SIP3 contain an N-terminal Bin/Amphiphysin/Rvs (BAR) domain followed by a PH domain. BAR domains form dimers that bind to membranes, induce membrane bending and curvature, and may also be involved in protein-protein interactions. PH domains have diverse functions, but in general are involved in targeting proteins to the appropriate cellular location or in the interaction with a binding partner. They share little sequence conservation, but all have a common fold, which is electrostatically polarized. Less than 10% of PH domains bind phosphoinositide phosphates (PIPs) with high affinity and specificity. PH domains are distinguished from other PIP-binding domains by their specific high-affinity binding to PIPs with two vicinal phosphate groups: PtdIns(3,4)P2, PtdIns(4,5)P2 or PtdIns(3,4,5)P3 which results in targeting some PH domain proteins to the plasma membrane. A few display strong specificity in lipid binding. Any specificity is usually determined by loop regions or insertions in the N-terminus of the domain, which are not conserved across all PH domains. PH domains are found in cellular signaling proteins such as serine/threonine kinase, tyrosine kinases, regulators of G-proteins, endocytotic GTPases, adaptors, as well as cytoskeletal associated molecules and in lipid associated enzymes.


Pssm-ID: 270098  Cd Length: 105  Bit Score: 41.09  E-value: 9.59e-05
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 115527076 110 KQGYLEKKSKDHSFFGSEWQKRWCVVSRGLFYYYANEKSKQ-----PK-GTFLIKgygVRMAPhlrrDSKKESCFELTSQ 183
Cdd:cd13280    2 KSGWLYMKTSVGKPNRTIWVRRWCFVKNGVFGMLSLSPSKTyveetDKfGVLLCS---VRYAP----EEDRRFCFEVKIF 74
                         90
                 ....*....|....*....
gi 115527076 184 DRRSYEFTATSPAEARDWV 202
Cdd:cd13280   75 KDISIILQAETLKELKSWL 93
SH3_PEX13_eumet cd11864
Src Homology 3 domain of eumetazoan Peroxisomal biogenesis factor 13; PEX13 is a peroxin and ...
299-348 9.59e-05

Src Homology 3 domain of eumetazoan Peroxisomal biogenesis factor 13; PEX13 is a peroxin and is required for protein import into the peroxisomal matrix and membrane. It is an integral membrane protein that is essential for the localization of PEX14 and the import of proteins containing the peroxisome matrix targeting signals, PTS1 and PTS2. Mutations of the PEX13 gene in humans lead to a wide range of peroxisome biogenesis disorders (PBDs), the most severe of which is known as Zellweger syndrome (ZS), a severe multisystem disorder characterized by hypotonia, psychomotor retardation, and neuronal migration defects. PEX13 contains two transmembrane regions and a C-terminal SH3 domain. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 212798  Cd Length: 58  Bit Score: 39.92  E-value: 9.59e-05
                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|...
gi 115527076 299 QGLWDCHGDQPDELSFQRGDLIRILSKEY--NMYGWWVGELN-SLVGIVPKEY 348
Cdd:cd11864    3 RAEYDFVAESEDELSFRAGDKLRLAPKELqpRVRGWLLATVDgQKIGLVPANY 55
SH3_Intersectin_1 cd11836
First Src homology 3 domain (or SH3A) of Intersectin; Intersectins (ITSNs) are adaptor ...
297-348 1.03e-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: 39.65  E-value: 1.03e-04
                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|..
gi 115527076 297 YYQGLWDCHGDQPDELSFQRGDLIRILSKEYNMYGWWVGELNSLVGIVPKEY 348
Cdd:cd11836    1 KYRALYAFEARNPDEISFQPGDIIQVDESQVAEPGWLAGELKGKTGWFPANY 52
SH3_GRB2_C cd11949
C-terminal Src homology 3 domain of Growth factor receptor-bound protein 2; GRB2 is a critical ...
297-350 1.06e-04

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


Pssm-ID: 212882 [Multi-domain]  Cd Length: 53  Bit Score: 39.44  E-value: 1.06e-04
                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|....*
gi 115527076 297 YYQGLWDCHGDQPDELSFQRGDLIRIL-SKEYNmygWWVGELNSLVGIVPKEYLT 350
Cdd:cd11949    1 YVQALFDFDPQEDGELGFRRGDFIEVMdNSDPN---WWKGACHGQTGMFPRNYVT 52
SH3_Nck_2 cd11766
Second Src Homology 3 domain of Nck adaptor proteins; Nck adaptor proteins regulate actin ...
308-350 1.11e-04

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


Pssm-ID: 212700 [Multi-domain]  Cd Length: 53  Bit Score: 39.56  E-value: 1.11e-04
                         10        20        30        40
                 ....*....|....*....|....*....|....*....|...
gi 115527076 308 QPDELSFQRGDLIRILSKEYNmyGWWVGELNSLVGIVPKEYLT 350
Cdd:cd11766   12 REDELSLRKGDRVLVLEKSSD--GWWRGECNGQVGWFPSNYVT 52
SH3_VAV3_2 cd11978
C-terminal (or second) Src homology 3 domain of VAV3 protein; VAV3 is ubiquitously expressed ...
311-349 1.11e-04

C-terminal (or second) Src homology 3 domain of VAV3 protein; VAV3 is ubiquitously expressed and functions as a phosphorylation-dependent guanine nucleotide exchange factor (GEF) for RhoA, RhoG, and Rac1. It has been implicated to function in the hematopoietic, bone, cerebellar, and cardiovascular systems. VAV3 is essential in axon guidance in neurons that control blood pressure and respiration. It is overexpressed in prostate cancer cells and it plays a role in regulating androgen receptor transcriptional activity. VAV proteins contain several domains that enable their function: N-terminal calponin homology (CH), acidic, RhoGEF (also called Dbl-homologous or DH), Pleckstrin Homology (PH), C1 (zinc finger), SH2, and two SH3 domains. The SH3 domain of VAV is involved in the localization of proteins to specific sites within the cell, by interacting with proline-rich sequences within target proteins. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 212911 [Multi-domain]  Cd Length: 56  Bit Score: 39.62  E-value: 1.11e-04
                         10        20        30
                 ....*....|....*....|....*....|....*....
gi 115527076 311 ELSFQRGDLIRILSKEyNMYGWWVGELNSLVGIVPKEYL 349
Cdd:cd11978   16 ELSLLKGDVVKIYTKM-STNGWWRGEVNGRVGWFPSTYV 53
PH2_Pleckstrin_2 cd13302
Pleckstrin 2 Pleckstrin homology (PH) domain, repeat 2; Pleckstrin is a protein found in ...
107-205 1.16e-04

Pleckstrin 2 Pleckstrin homology (PH) domain, repeat 2; Pleckstrin is a protein found in platelets. This name is derived from platelet and leukocyte C kinase substrate and the KSTR string of amino acids. Pleckstrin 2 contains two PH domains and a DEP (dishvelled, egl-10, and pleckstrin) domain. Unlike pleckstrin 1, pleckstrin 2 does not contain obvious sites of PKC phosphorylation. Pleckstrin 2 plays a role in actin rearrangement, large lamellipodia and peripheral ruffle formation, and may help orchestrate cytoskeletal arrangement. The PH domains of pleckstrin 2 are thought to contribute to lamellipodia formation. This cd contains the second PH domain repeat. PH domains have diverse functions, but in general are involved in targeting proteins to the appropriate cellular location or in the interaction with a binding partner. They share little sequence conservation, but all have a common fold, which is electrostatically polarized. Less than 10% of PH domains bind phosphoinositide phosphates (PIPs) with high affinity and specificity. PH domains are distinguished from other PIP-binding domains by their specific high-affinity binding to PIPs with two vicinal phosphate groups: PtdIns(3,4)P2, PtdIns(4,5)P2 or PtdIns(3,4,5)P3 which results in targeting some PH domain proteins to the plasma membrane. A few display strong specificity in lipid binding. Any specificity is usually determined by loop regions or insertions in the N-terminus of the domain, which are not conserved across all PH domains. PH domains are found in cellular signaling proteins such as serine/threonine kinase, tyrosine kinases, regulators of G-proteins, endocytotic GTPases, adaptors, as well as cytoskeletal associated molecules and in lipid associated enzymes.


Pssm-ID: 270114  Cd Length: 109  Bit Score: 40.96  E-value: 1.16e-04
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 115527076 107 NVIKQGYLEKKSKDHsffgsEWQKRWCVVSR---GLFYYYANEKSKQPKGTFLIKG---YGVRMAPHLRRDSKKESCFEL 180
Cdd:cd13302    6 IIVKQGCLLKQGHRR-----KNWKVRKFVLRddpAYLHYYDPAKGEDPLGAIHLRGcvvTAVEDNSNPRKGSVEGNLFEI 80
                         90       100
                 ....*....|....*....|....*
gi 115527076 181 TSQDRRSYEFTATSPAEARDWVDQI 205
Cdd:cd13302   81 ITADEVHYYLQAATPAERTEWIKAI 105
PH_Osh1p_Osh2p_yeast cd13292
Yeast oxysterol binding protein homologs 1 and 2 Pleckstrin homology (PH) domain; Yeast Osh1p ...
112-206 1.30e-04

Yeast oxysterol binding protein homologs 1 and 2 Pleckstrin homology (PH) domain; Yeast Osh1p is proposed to function in postsynthetic sterol regulation, piecemeal microautophagy of the nucleus, and cell polarity establishment. Yeast Osh2p is proposed to function in sterol metabolism and cell polarity establishment. Both Osh1p and Osh2p contain 3 N-terminal ankyrin repeats, a PH domain, a FFAT motif (two phenylalanines in an acidic tract), and a C-terminal OSBP-related domain. OSBP andOsh1p PH domains specifically localize to the Golgi apparatus in a PtdIns4P-dependent manner. Oxysterol binding proteins are a multigene family that is conserved in yeast, flies, worms, mammals and plants. In general OSBPs and ORPs have been found to be involved in the transport and metabolism of cholesterol and related lipids in eukaryotes. They all contain a C-terminal oxysterol binding domain, and most contain an N-terminal PH domain. OSBP PH domains bind to membrane phosphoinositides and thus likely play an important role in intracellular targeting. They are members of the oxysterol binding protein (OSBP) family which includes OSBP, OSBP-related proteins (ORP), Goodpasture antigen binding protein (GPBP), and Four phosphate adaptor protein 1 (FAPP1). They have a wide range of purported functions including sterol transport, cell cycle control, pollen development and vessicle transport from Golgi recognize both PI lipids and ARF proteins. PH domains have diverse functions, but in general are involved in targeting proteins to the appropriate cellular location or in the interaction with a binding partner. They share little sequence conservation, but all have a common fold, which is electrostatically polarized. Less than 10% of PH domains bind phosphoinositide phosphates (PIPs) with high affinity and specificity. PH domains are distinguished from other PIP-binding domains by their specific high-affinity binding to PIPs with two vicinal phosphate groups: PtdIns(3,4)P2, PtdIns(4,5)P2 or PtdIns(3,4,5)P3 which results in targeting some PH domain proteins to the plasma membrane. A few display strong specificity in lipid binding. Any specificity is usually determined by loop regions or insertions in the N-terminus of the domain, which are not conserved across all PH domains. PH domains are found in cellular signaling proteins such as serine/threonine kinase, tyrosine kinases, regulators of G-proteins, endocytotic GTPases, adaptors, as well as cytoskeletal associated molecules and in lipid associated enzymes.


Pssm-ID: 241446  Cd Length: 103  Bit Score: 40.75  E-value: 1.30e-04
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 115527076 112 GYLEKKSKdhsfFGSEWQKRWCVVSRGLFYYYANEK--SKQPKGTFLIKGYGVRMaphlrrDSKKESCFELTSQDRRSYE 189
Cdd:cd13292    6 GYLKKWTN----YAKGYKTRWFVLEDGVLSYYRHQDdeGSACRGSINMKNARLVS------DPSEKLRFEVSSKTSGSPK 75
                         90
                 ....*....|....*....
gi 115527076 190 FT--ATSPAEARDWVDQIS 206
Cdd:cd13292   76 WYlkANHPVEAARWIQALQ 94
SH3_Eve1_4 cd11817
Fourth Src homology 3 domain of ADAM-binding protein Eve-1; Eve-1, also called SH3 ...
301-348 1.30e-04

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


Pssm-ID: 212751 [Multi-domain]  Cd Length: 50  Bit Score: 39.38  E-value: 1.30e-04
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                 ....*....|....*....|....*....|....*....|....*...
gi 115527076 301 LWDCHGDQPDELSFQRGDLIRILskEYNMYGWWVGELNSLVGIVPKEY 348
Cdd:cd11817    5 LYDFTGETEEDLSFQRGDRILVT--EHLDAEWSRGRLNGREGIFPRAF 50
SH3_Eve1_3 cd11816
Third Src homology 3 domain of ADAM-binding protein Eve-1; Eve-1, also called SH3 ...
301-348 1.42e-04

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


Pssm-ID: 212750 [Multi-domain]  Cd Length: 51  Bit Score: 38.93  E-value: 1.42e-04
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gi 115527076 301 LWDCHGDQPDELSFQRGDLIRIlsKEYNMYGWWVGELNSLVGIVPKEY 348
Cdd:cd11816    5 RFDFEGEQEDELSFSEGDVITL--KEYVGEEWAKGELNGKIGIFPLNF 50
SH3_MYO15 cd11884
Src Homology 3 domain of Myosin XV; This subfamily is composed of proteins with similarity to ...
312-348 1.46e-04

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


Pssm-ID: 212817 [Multi-domain]  Cd Length: 56  Bit Score: 39.23  E-value: 1.46e-04
                         10        20        30
                 ....*....|....*....|....*....|....*...
gi 115527076 312 LSFQRGDLIRILSKE-YNMYGWWVGELNSLVGIVPKEY 348
Cdd:cd11884   16 LSFHKGDVIKLLPKEgPLDPGWLFGTLDGRSGAFPKEY 53
SH3_CASS4 cd12000
Src homology 3 domain of CAS (Crk-Associated Substrate) scaffolding protein family member 4; ...
299-349 1.59e-04

Src homology 3 domain of CAS (Crk-Associated Substrate) scaffolding protein family member 4; CASS4, also called HEPL (HEF1-EFS-p130Cas-like), localizes to focal adhesions and plays a role in regulating FAK activity, focal adhesion integrity, and cell spreading. It is most abundant in blood cells and lung tissue, and is also found in high levels in leukemia and ovarian cell lines. CAS proteins function as molecular scaffolds to regulate protein complexes that are involved in many cellular processes. They share a common domain structure that includes an N-terminal SH3 domain, an unstructured substrate domain that contains many YxxP motifs, a serine-rich four-helix bundle, and a FAT-like C-terminal domain. The SH3 domain of CAS proteins binds to diverse partners including FAK, FRNK, Pyk2, PTP-PEST, DOCK180, among others. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 212933  Cd Length: 57  Bit Score: 39.09  E-value: 1.59e-04
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gi 115527076 299 QGLWDCHGDQPDELSFQRGDLIRILSKEY-NMYGWWVGELNSLVGIVPKEYL 349
Cdd:cd12000    4 RALYDNKADCSDELAFRRGDILTVLEQNVpGSEGWWKCLLHGRQGLAPANRL 55
SH3_Intersectin_4 cd11839
Fourth Src homology 3 domain (or SH3D) of Intersectin; Intersectins (ITSNs) are adaptor ...
309-348 1.81e-04

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


Pssm-ID: 212773 [Multi-domain]  Cd Length: 58  Bit Score: 38.86  E-value: 1.81e-04
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gi 115527076 309 PDELSFQRGDLIRILSKEYNmyGWWVGELNS-----LVGIVPKEY 348
Cdd:cd11839   13 ENQLSLAVGQLVLVRKKSPS--GWWEGELQArgkkrQIGWFPANY 55
PH_OPR5_ORP8 cd13286
Human Oxysterol binding protein related proteins 5 and 8 Pleckstrin homology (PH) domain; ...
128-180 1.98e-04

Human Oxysterol binding protein related proteins 5 and 8 Pleckstrin homology (PH) domain; Human ORP5 is proposed to function in efficient nonvesicular transfer of low-density lipoproteins-derived cholesterol (LDL-C) from late endosomes/lysosomes to the endoplasmic reticulum (ER). Human ORP8 is proposed to modulate lipid homeostasis and sterol regulatory element binding proteins (SREBP) activity. Both ORP5 and ORP8 contain a N-terminal PH domain, a C-terminal OSBP-related domain, followed by a transmembrane domain that localizes ORP5 to the ER. Unlike all the other human OSBP/ORPs they lack a FFAT motif (two phenylalanines in an acidic tract). Oxysterol binding proteins are a multigene family that is conserved in yeast, flies, worms, mammals and plants. In general OSBPs and ORPs have been found to be involved in the transport and metabolism of cholesterol and related lipids in eukaryotes. They all contain a C-terminal oxysterol binding domain, and most contain an N-terminal PH domain. OSBP PH domains bind to membrane phosphoinositides and thus likely play an important role in intracellular targeting. They are members of the oxysterol binding protein (OSBP) family which includes OSBP, OSBP-related proteins (ORP), Goodpasture antigen binding protein (GPBP), and Four phosphate adaptor protein 1 (FAPP1). They have a wide range of purported functions including sterol transport, cell cycle control, pollen development and vessicle transport from Golgi recognize both PI lipids and ARF proteins. PH domains have diverse functions, but in general are involved in targeting proteins to the appropriate cellular location or in the interaction with a binding partner. They share little sequence conservation, but all have a common fold, which is electrostatically polarized. Less than 10% of PH domains bind phosphoinositide phosphates (PIPs) with high affinity and specificity. PH domains are distinguished from other PIP-binding domains by their specific high-affinity binding to PIPs with two vicinal phosphate groups: PtdIns(3,4)P2, PtdIns(4,5)P2 or PtdIns(3,4,5)P3 which results in targeting some PH domain proteins to the plasma membrane. A few display strong specificity in lipid binding. Any specificity is usually determined by loop regions or insertions in the N-terminus of the domain, which are not conserved across all PH domains. PH domains are found in cellular signaling proteins such as serine/threonine kinase, tyrosine kinases, regulators of G-proteins, endocytotic GTPases, adaptors, as well as cytoskeletal associated molecules and in lipid associated enzymes.


Pssm-ID: 270103  Cd Length: 130  Bit Score: 40.80  E-value: 1.98e-04
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gi 115527076 128 WQKRWCVVSRGLFYYYANEKSKQPKGTFLIKGYGVrmaphLRRDSKKES-CFEL 180
Cdd:cd13286   23 WTKLWCVLKPGVLLLYKSPKHGQWVGTVLLNACEV-----IERPSKKDGfCFKL 71
SH3_Abi2 cd11972
Src homology 3 domain of Abl Interactor 2; Abi2 is highly expressed in the brain and eye. It ...
300-351 2.11e-04

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


Pssm-ID: 212905 [Multi-domain]  Cd Length: 61  Bit Score: 38.84  E-value: 2.11e-04
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gi 115527076 300 GLWDCHGDQPDELSFQRGDLIRILSKeyNMYGWWVGELNSLVGIVPKEYLTT 351
Cdd:cd11972    7 AIYDYTKDKEDELSFQEGAIIYVIKK--NDDGWYEGVMNGVTGLFPGNYVES 56
SH3_betaPIX cd12061
Src Homology 3 domain of beta-Pak Interactive eXchange factor; Beta-PIX, also called Rho ...
310-349 2.14e-04

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


Pssm-ID: 212994 [Multi-domain]  Cd Length: 54  Bit Score: 38.90  E-value: 2.14e-04
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gi 115527076 310 DELSFQRGDLIRILSKEYNmyGWWVGELNSLVGIVPKEYL 349
Cdd:cd12061   14 DELSFSKGDVIHVTRVEEG--GWWEGTHNGRTGWFPSNYV 51
PH_Gab2_2 cd13384
Grb2-associated binding protein family pleckstrin homology (PH) domain; The Gab subfamily ...
106-205 2.44e-04

Grb2-associated binding protein family pleckstrin homology (PH) domain; The Gab subfamily includes several Gab proteins, Drosophila DOS and C. elegans SOC-1. They are scaffolding adaptor proteins, which possess N-terminal PH domains and a C-terminus with proline-rich regions and multiple phosphorylation sites. Following activation of growth factor receptors, Gab proteins are tyrosine phosphorylated and activate PI3K, which generates 3-phosphoinositide lipids. By binding to these lipids via the PH domain, Gab proteins remain in proximity to the receptor, leading to further signaling. While not all Gab proteins depend on the PH domain for recruitment, it is required for Gab activity. Members here include insect, nematodes, and crustacean Gab2s. PH domains have diverse functions, but in general are involved in targeting proteins to the appropriate cellular location or in the interaction with a binding partner. They share little sequence conservation, but all have a common fold, which is electrostatically polarized. Less than 10% of PH domains bind phosphoinositide phosphates (PIPs) with high affinity and specificity. PH domains are distinguished from other PIP-binding domains by their specific high-affinity binding to PIPs with two vicinal phosphate groups: PtdIns(3,4)P2, PtdIns(4,5)P2 or PtdIns(3,4,5)P3 which results in targeting some PH domain proteins to the plasma membrane. A few display strong specificity in lipid binding. Any specificity is usually determined by loop regions or insertions in the N-terminus of the domain, which are not conserved across all PH domains. PH domains are found in cellular signaling proteins such as serine/threonine kinase, tyrosine kinases, regulators of G-proteins, endocytotic GTPases, adaptors, as well as cytoskeletal associated molecules and in lipid associated enzymes.


Pssm-ID: 241535  Cd Length: 115  Bit Score: 40.12  E-value: 2.44e-04
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gi 115527076 106 DNVIKQGYLEKKSKDHSFFGSEWQKRWCVVSRG------LFYYYANEKSKQPKGTF-LIKGYGVRMAPHLRRDSKKESCF 178
Cdd:cd13384    1 TEVVYEGWLTKSPPEKRIWRAKWRRRYFVLRQSeipgqyFLEYYTDRTCRKLKGSIdLDQCEQVDAGLTFETKNKLKDQH 80
                         90       100
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gi 115527076 179 ELTSQ-DRRSYEFTATSPAEARDWVDQI 205
Cdd:cd13384   81 IFDIRtPKRTYYLVADTEDEMNKWVNCI 108
SH3_MyoIe_If_like cd11827
Src homology 3 domain of Myosins Ie, If, and similar proteins; Myosins Ie (MyoIe) and If ...
299-350 2.67e-04

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


Pssm-ID: 212761 [Multi-domain]  Cd Length: 53  Bit Score: 38.55  E-value: 2.67e-04
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gi 115527076 299 QGLWDCHGDQPDELSFQRGDLIRILSKEYNmyGWWVGELNSLVGIVPKEYLT 350
Cdd:cd11827    3 KALYAYDAQDTDELSFNEGDIIEILKEDPS--GWWTGRLRGKEGLFPGNYVE 52
SH3_STAM1 cd11964
Src homology 3 domain of Signal Transducing Adaptor Molecule 1; STAM1 is part of the endosomal ...
299-351 3.12e-04

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


Pssm-ID: 212897 [Multi-domain]  Cd Length: 55  Bit Score: 38.39  E-value: 3.12e-04
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gi 115527076 299 QGLWDCHGDQPDELSFQRGDLIRILSKeyNMYGWWVGELNSLVGIVPKEYLTT 351
Cdd:cd11964    4 RAIYDFEAAEDNELTFKAGDIITILDD--SDPNWWKGETPQGTGLFPSNFVTA 54
SH3_ARHGEF9_like cd11828
Src homology 3 domain of ARHGEF9-like Rho guanine nucleotide exchange factors; Members of this ...
301-349 3.39e-04

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


Pssm-ID: 212762 [Multi-domain]  Cd Length: 53  Bit Score: 38.13  E-value: 3.39e-04
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gi 115527076 301 LWDCHGDQPDELSFQRGDLIRILskEYNMYGWWVGELNSLVGIVPKEYL 349
Cdd:cd11828    5 LWDHVTMDPEELGFKAGDVIEVL--DMSDKDWWWGSIRDEEGWFPASFV 51
SH3_VAV2_2 cd11977
C-terminal (or second) Src homology 3 domain of VAV2 protein; VAV2 is widely expressed and ...
311-349 3.71e-04

C-terminal (or second) Src homology 3 domain of VAV2 protein; VAV2 is widely expressed and functions as a guanine nucleotide exchange factor (GEF) for RhoA, RhoB and RhoG and also activates Rac1 and Cdc42. It is implicated in many cellular and physiological functions including blood pressure control, eye development, neurite outgrowth and branching, EGFR endocytosis and degradation, and cell cluster morphology, among others. It has been reported to associate with Nek3. VAV proteins contain several domains that enable their function: N-terminal calponin homology (CH), acidic, RhoGEF (also called Dbl-homologous or DH), Pleckstrin Homology (PH), C1 (zinc finger), SH2, and two SH3 domains. The SH3 domain of VAV is involved in the localization of proteins to specific sites within the cell, by interacting with proline-rich sequences within target proteins. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 212910 [Multi-domain]  Cd Length: 58  Bit Score: 38.07  E-value: 3.71e-04
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gi 115527076 311 ELSFQRGDLIRILSKEYNMYGWWVGELNSLVGIVPKEYL 349
Cdd:cd11977   16 ELSLREGDVVRIYSRIGGDQGWWKGETNGRIGWFPSTYV 54
SH3_ASAP2 cd11966
Src homology 3 domain of ArfGAP with SH3 domain, ankyrin repeat and PH domain containing ...
299-338 7.04e-04

Src homology 3 domain of ArfGAP with SH3 domain, ankyrin repeat and PH domain containing protein 2; ASAP2 is also called DDEF2 (Development and Differentiation Enhancing Factor 2), AMAP2, centaurin beta-3, or PAG3. It mediates the functions of Arf GTPases vial dual mechanisms: it exhibits GTPase activating protein (GAP) activity towards class I (Arf1) and II (Arf5) Arfs; and it binds class III Arfs (GTP-Arf6) stably without GAP activity. It binds paxillin and is implicated in Fcgamma receptor-mediated phagocytosis in macrophages and in cell migration. ASAP2 contains an N-terminal BAR domain, followed by a Pleckstrin homology (PH) domain, an Arf GAP domain, ankyrin (ANK) repeats, and a C-terminal SH3 domain. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 212899  Cd Length: 56  Bit Score: 37.24  E-value: 7.04e-04
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gi 115527076 299 QGLWDCHGDQPDELSFQRGDLIRILSKEYNMygWWVGELN 338
Cdd:cd11966    3 KALYNCVADNPDELTFSEGEIIIVDGEEDKE--WWIGHID 40
SH3_SNX9_like cd11763
Src Homology 3 domain of Sorting Nexin 9 and similar proteins; Sorting nexins (SNXs) are Phox ...
297-351 7.06e-04

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: 37.31  E-value: 7.06e-04
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gi 115527076 297 YYQGLWDCHGDQPDELSFQRGDLIRILSkEYNMYGWWVGE-LNSLVGIVPKEYLTT 351
Cdd:cd11763    1 KVRALYDFDSQPSGELSLRAGEVLTITR-QDVGDGWLEGRnSRGEVGLFPSSYVEI 55
SH3_Intersectin2_3 cd11992
Third Src homology 3 domain (or SH3C) of Intersectin-2; Intersectin-2 (ITSN2) is an adaptor ...
298-351 7.37e-04

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


Pssm-ID: 212925  Cd Length: 52  Bit Score: 37.30  E-value: 7.37e-04
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gi 115527076 298 YQGLWDCHGDQPDELSFQRGDLIRILSKEYNmygWWVGELNSLVGIVPKEYLTT 351
Cdd:cd11992    2 YIALYPYSSSEPGDLTFNEGEEILVTQKDGE---WWTGSIEDRTGIFPSNYVRP 52
PH_Gab-like cd13324
Grb2-associated binding protein family Pleckstrin homology (PH) domain; Gab proteins are ...
108-206 7.61e-04

Grb2-associated binding protein family Pleckstrin homology (PH) domain; Gab proteins are scaffolding adaptor proteins, which possess N-terminal PH domains and a C-terminus with proline-rich regions and multiple phosphorylation sites. Following activation of growth factor receptors, Gab proteins are tyrosine phosphorylated and activate PI3K, which generates 3-phosphoinositide lipids. By binding to these lipids via the PH domain, Gab proteins remain in proximity to the receptor, leading to further signaling. While not all Gab proteins depend on the PH domain for recruitment, it is required for Gab activity. There are 3 families: Gab1, Gab2, and Gab3. PH domains have diverse functions, but in general are involved in targeting proteins to the appropriate cellular location or in the interaction with a binding partner. They share little sequence conservation, but all have a common fold, which is electrostatically polarized. Less than 10% of PH domains bind phosphoinositide phosphates (PIPs) with high affinity and specificity. PH domains are distinguished from other PIP-binding domains by their specific high-affinity binding to PIPs with two vicinal phosphate groups: PtdIns(3,4)P2, PtdIns(4,5)P2 or PtdIns(3,4,5)P3 which results in targeting some PH domain proteins to the plasma membrane. A few display strong specificity in lipid binding. Any specificity is usually determined by loop regions or insertions in the N-terminus of the domain, which are not conserved across all PH domains. PH domains are found in cellular signaling proteins such as serine/threonine kinase, tyrosine kinases, regulators of G-proteins, endocytotic GTPases, adaptors, as well as cytoskeletal associated molecules and in lipid associated enzymes.


Pssm-ID: 270133  Cd Length: 112  Bit Score: 38.55  E-value: 7.61e-04
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gi 115527076 108 VIKQGYLEKKSKDHSFFGSEWQKRWCVVSRG-------LFYYYANEKSKQPKGTF------LIKGYGvrmaPHLRRDSKK 174
Cdd:cd13324    1 VVYEGWLTKSPPEKKIWRAAWRRRWFVLRSGrlsggqdVLEYYTDDHCKKLKGIIdldqceQVDAGL----TFEKKKFKN 76
                         90       100       110
                 ....*....|....*....|....*....|..
gi 115527076 175 ESCFELTSQDRRSYeFTATSPAEARDWVDQIS 206
Cdd:cd13324   77 QFIFDIRTPKRTYY-LVAETEEEMNKWVRCIC 107
SH3_STAM2 cd11963
Src homology 3 domain of Signal Transducing Adaptor Molecule 2; STAM2, also called EAST ...
299-351 7.70e-04

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


Pssm-ID: 212896 [Multi-domain]  Cd Length: 57  Bit Score: 37.31  E-value: 7.70e-04
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                 ....*....|....*....|....*....|....*....|....*....|...
gi 115527076 299 QGLWDCHGDQPDELSFQRGDLIRILSKeyNMYGWWVGELNSLVGIVPKEYLTT 351
Cdd:cd11963    5 RALYDFEAVEDNELTFKHGEIIIVLDD--SDANWWKGENHRGVGLFPSNFVTT 55
SH3_GRAP2_C cd11950
C-terminal Src homology 3 domain of GRB2-related adaptor protein 2; GRAP2 is also called GADS ...
301-348 7.85e-04

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


Pssm-ID: 212883 [Multi-domain]  Cd Length: 53  Bit Score: 37.11  E-value: 7.85e-04
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gi 115527076 301 LWDCHGDQPDELSFQRGDLIRILSKEYNmyGWWVGELNSLVGIVPKEY 348
Cdd:cd11950    5 LYDFEALEDDELGFNSGDVIEVLDSSNP--SWWKGRLHGKLGLFPANY 50
SH3_SH3RF_1 cd11786
First Src Homology 3 domain of SH3 domain containing ring finger proteins; This model ...
297-348 7.85e-04

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


Pssm-ID: 212720 [Multi-domain]  Cd Length: 53  Bit Score: 36.96  E-value: 7.85e-04
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gi 115527076 297 YYQGLWDCHGDQPDELSFQRGDLIrILSKEYNMyGWWVGELNSLVGIVPKEY 348
Cdd:cd11786    1 CAKALYNYEGKEPGDLSFKKGDII-LLRKRIDE-NWYHGECNGKQGFFPASY 50
SH3_SH3RF2_1 cd11929
First Src Homology 3 domain of SH3 domain containing ring finger 2; SH3RF2 is also called ...
299-345 8.03e-04

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


Pssm-ID: 212862  Cd Length: 54  Bit Score: 37.23  E-value: 8.03e-04
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gi 115527076 299 QGLWDCHGDQPDELSFQRGDLIrILSKEYNMyGWWVGELNSLVGIVP 345
Cdd:cd11929    4 KALCNYRGHNPGDLKFNKGDVI-LLRRQLDE-NWYLGEINGVSGIFP 48
SH3_p47phox_like cd11856
Src homology 3 domains of the p47phox subunit of NADPH oxidase and similar domains; This ...
306-349 8.23e-04

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


Pssm-ID: 212790 [Multi-domain]  Cd Length: 53  Bit Score: 36.85  E-value: 8.23e-04
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gi 115527076 306 GDQPDELSFQRGDLIRILSKeyNMYGWWVGELNSLVGIVPKEYL 349
Cdd:cd11856   10 AQGDDEISLQEGEVVEVLEK--NDSGWWYVRKGDKEGWVPASYL 51
SH3_Bzz1_2 cd11778
Second Src Homology 3 domain of Bzz1 and similar domains; Bzz1 (or Bzz1p) is a WASP ...
297-348 8.38e-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: 37.09  E-value: 8.38e-04
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gi 115527076 297 YYQGLWDCHGDQPDELSFQRGDLIRILsKEYNMYGWWVGELNSLVGIVPKEY 348
Cdd:cd11778    1 YVEALYDYEAQGDDEISIRVGDRIAVI-RGDDGSGWTYGEINGVKGLFPTSY 51
SH3_HS1 cd12073
Src homology 3 domain of Hematopoietic lineage cell-specific protein 1; HS1, also called HCLS1 ...
301-349 9.04e-04

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


Pssm-ID: 213006 [Multi-domain]  Cd Length: 55  Bit Score: 37.12  E-value: 9.04e-04
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gi 115527076 301 LWDCHGDQPDELSFQRGDLIRILskEYNMYGWWVGELNSLVGIVPKEYL 349
Cdd:cd12073    6 LYDYQGEGDDEISFDPQETITDI--EMVDEGWWKGTCHGHRGLFPANYV 52
SH3_CRK_N cd11758
N-terminal Src Homology 3 domain of Ct10 Regulator of Kinase adaptor proteins; CRK adaptor ...
297-350 9.08e-04

N-terminal Src Homology 3 domain of Ct10 Regulator of Kinase adaptor proteins; CRK adaptor proteins consists of SH2 and SH3 domains, which bind tyrosine-phosphorylated peptides and proline-rich motifs, respectively. They function downstream of protein tyrosine kinases in many signaling pathways started by various extracellular signals, including growth and differentiation factors. Cellular CRK (c-CRK) contains a single SH2 domain, followed by N-terminal and C-terminal SH3 domains. It is involved in the regulation of many cellular processes including cell growth, motility, adhesion, and apoptosis. CRK has been implicated in the malignancy of various human cancers. The N-terminal SH3 domain of CRK binds a number of target proteins including DOCK180, C3G, SOS, and cABL. The CRK family includes two alternatively spliced protein forms, CRKI and CRKII, that are expressed by the CRK gene, and the CRK-like (CRKL) protein, which is expressed by a distinct gene (CRKL). SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 212692 [Multi-domain]  Cd Length: 55  Bit Score: 36.96  E-value: 9.08e-04
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gi 115527076 297 YYQGLWDCHGDQPDELSFQRGDLIRILSKEYNMygWWVGElNSL--VGIVPKEYLT 350
Cdd:cd11758    2 YVRALFDFPGNDDEDLPFKKGEILTVIRKPEEQ--WWNAR-NSEgkTGMIPVPYVE 54
SH3_AHI-1 cd11812
Src Homology 3 domain of Abelson helper integration site-1 (AHI-1); AHI-1, also called ...
301-349 1.01e-03

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


Pssm-ID: 212746 [Multi-domain]  Cd Length: 52  Bit Score: 36.72  E-value: 1.01e-03
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gi 115527076 301 LWDCHGDQPDELSFQRGDLIRILSKEYNmyGWWVGEL-NSLVGIVPKEYL 349
Cdd:cd11812    5 LYDYTANRSDELTIHRGDIIRVLYKDND--NWWFGSLvNGQQGYFPANYV 52
SH3_Myosin-I_fungi cd11858
Src homology 3 domain of Type I fungal Myosins; Type I myosins (myosin-I) are actin-dependent ...
298-350 1.05e-03

Src homology 3 domain of Type I fungal Myosins; Type I myosins (myosin-I) are actin-dependent motors in endocytic actin structures and actin patches. They play roles in membrane traffic in endocytic and secretory pathways, cell motility, and mechanosensing. Saccharomyces cerevisiae has two myosins-I, Myo3 and Myo5, which are involved in endocytosis and the polarization of the actin cytoskeleton. Myosin-I contains an N-terminal actin-activated ATPase, a phospholipid-binding TH1 (tail homology 1) domain, and a C-terminal extension which includes an F-actin-binding TH2 domain, an SH3 domain, and an acidic peptide that participates in activating the Arp2/3complex. The SH3 domain of myosin-I is required for myosin-I-induced actin polymerization. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 212792 [Multi-domain]  Cd Length: 55  Bit Score: 36.59  E-value: 1.05e-03
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gi 115527076 298 YQGLWDCHGDQPDELSFQRGDLIRILSKEYNmyGWWVGELN--SLVGIVPKEYLT 350
Cdd:cd11858    2 YKALYDFAGSVANELSLKKDDIVYIVQKEDN--GWWLAKKLdeSKEGWVPAAYLE 54
SH3_Intersectin_2 cd11837
Second Src homology 3 domain (or SH3B) of Intersectin; Intersectins (ITSNs) are adaptor ...
306-351 1.16e-03

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


Pssm-ID: 212771 [Multi-domain]  Cd Length: 53  Bit Score: 36.57  E-value: 1.16e-03
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gi 115527076 306 GDQPDELSFQRGDLIRILSKEYNmygWWVGELNSL-VGIVPKEYLTT 351
Cdd:cd11837   10 AKKENHLSFAKGDIITVLEQQEM---WWFGELEGGeEGWFPKSYVKE 53
PH_GAP1_mammal-like cd13371
GAP1(IP4BP) pleckstrin homology (PH) domain; GAP1 (also called IP4BP, RASA3/Ras ...
108-203 1.25e-03

GAP1(IP4BP) pleckstrin homology (PH) domain; GAP1 (also called IP4BP, RASA3/Ras GTPase-activating protein 3, and RAS p21 protein activator (GTPase activating protein) 3/GAPIII/MGC46517/MGC47588)) is a member of the GAP1 family of GTPase-activating proteins, along with RASAL1, GAP1(m), and CAPRI. With the notable exception of GAP1(m), they all possess an arginine finger-dependent GAP activity on the Ras-related protein Rap1. GAP1(IP4BP) contains two C2 domains, a PH domain, a RasGAP domain, and a BTK domain. Its C2 domains, like those of GAP1M, do not contain the C2 motif that is known to be required for calcium-dependent phospholipid binding. GAP1(IP4BP) is regulated by the binding of its PH domains to phophoinositides, PIP3 (phosphatidylinositol 3,4,5-trisphosphate) and PIP2 (phosphatidylinositol 4,5-bisphosphate). It suppresses RAS, enhancing the weak intrinsic GTPase activity of RAS proteins resulting in the inactive GDP-bound form of RAS, allowing control of cellular proliferation and differentiation. GAP1(IP4BP) binds tyrosine-protein kinase, HCK. Members here include humans, chickens, frogs, and fish. PH domains have diverse functions, but in general are involved in targeting proteins to the appropriate cellular location or in the interaction with a binding partner. They share little sequence conservation, but all have a common fold, which is electrostatically polarized. Less than 10% of PH domains bind phosphoinositide phosphates (PIPs) with high affinity and specificity. PH domains are distinguished from other PIP-binding domains by their specific high-affinity binding to PIPs with two vicinal phosphate groups: PtdIns(3,4)P2, PtdIns(4,5)P2 or PtdIns(3,4,5)P3 which results in targeting some PH domain proteins to the plasma membrane. A few display strong specificity in lipid binding. Any specificity is usually determined by loop regions or insertions in the N-terminus of the domain, which are not conserved across all PH domains. PH domains are found in cellular signaling proteins such as serine/threonine kinase, tyrosine kinases, regulators of G-proteins, endocytotic GTPases, adaptors, as well as cytoskeletal associated molecules and in lipid associated enzymes.


Pssm-ID: 241522  Cd Length: 125  Bit Score: 38.48  E-value: 1.25e-03
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gi 115527076 108 VIKQGYLEKKSKDHSFFG-SEWQKRWCVVSRGLFYYYaneKSKQPKGTFLIKGYGVRMAPHLRRDS-KKESCFELTSQDR 185
Cdd:cd13371   16 LLKEGFMIKRAQGRKRFGmKNFKKRWFRLTNHEFTYH---KSKGDHPLCSIPIENILAVERLEEESfKMKNMFQVIQPER 92
                         90
                 ....*....|....*...
gi 115527076 186 RSYeFTATSPAEARDWVD 203
Cdd:cd13371   93 ALY-IQANNCVEAKDWID 109
SH3_PLCgamma2 cd11969
Src homology 3 domain of Phospholipase C (PLC) gamma 2; PLCgamma2 is primarily expressed in ...
299-336 1.42e-03

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


Pssm-ID: 212902  Cd Length: 55  Bit Score: 36.36  E-value: 1.42e-03
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gi 115527076 299 QGLWDCHGDQPDELSFQRGDLIRILSKEYNmyGWWVGE 336
Cdd:cd11969    3 KALYDYRAKRSDELSFCKGALIHNVSKETG--GWWKGD 38
SH3_Sorbs2_1 cd11920
First Src Homology 3 domain of Sorbin and SH3 domain containing 2 (Sorbs2), also called ...
299-349 1.43e-03

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


Pssm-ID: 212853 [Multi-domain]  Cd Length: 55  Bit Score: 36.53  E-value: 1.43e-03
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gi 115527076 299 QGLWDCHGDQPDELSFQRGDLIRILSKEYNmyGWWVGELNSLVGIVPKEYL 349
Cdd:cd11920    4 RAVYDFKAQTSKELSFKKGDTVYILRKIDQ--NWYEGEHHGRVGIFPISYV 52
Niban-like cd23949
Niban-like protein; Niban-like proteins contain an N-terminal Pleckstrin-Homology (PH) domain ...
104-206 1.50e-03

Niban-like protein; Niban-like proteins contain an N-terminal Pleckstrin-Homology (PH) domain that may be involved in binding to specific ligands. Phosphatidylinositol (3)-phosphate (PI3P) was recognized as the innate ligand of the PH domain of MINERVA (melanoma invasion by ERK, also known as FAM129B) PH. Niban family proteins have been found to regulate phosphorylation of a number of proteins involved in the regularion of translation, such as EIF2A, EIF4EBP1 and RPS6KB1. They may also be involved in the endoplasmic reticulum stress response (FAM129A, Niban-like protein 1), suggested to play a role in apoptosis suppression in cancer cells, while Niban-like protein 2 (FAM129C) is a B-cell membrane protein that is overexpressed in chronic lymphocytic leukemia.


Pssm-ID: 469558 [Multi-domain]  Cd Length: 550  Bit Score: 40.36  E-value: 1.50e-03
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                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 115527076 104 ELDNVIKQGYLEKKSKDhsffGSEWQKRWCVV--SRGLFYY---YANEKSKQPKGTFLIKGYGV------------RMAP 166
Cdd:cd23949   58 EDRKVIFSGKLSKYGED----SKKWKERFCVVrgDYNLEYYeskEAYERGKKPKGSINLAGYKVltspeeylelvdRKFP 133
                         90       100       110       120       130
                 ....*....|....*....|....*....|....*....|....*....|
gi 115527076 167 HLRRDSKKESC----------FELTSQDRRSYEFTATSPAEARDWVDQIS 206
Cdd:cd23949  134 DLAGKSEKASVpfperpppftLELYHPYRRHYYFCFETEKEQEEWVAVLQ 183
PH_PLD cd01254
Phospholipase D pleckstrin homology (PH) domain; PLD hydrolyzes phosphatidylcholine to ...
110-205 1.57e-03

Phospholipase D pleckstrin homology (PH) domain; PLD hydrolyzes phosphatidylcholine to phosphatidic acid (PtdOH), which can bind target proteins. PLD contains a PH domain, a PX domain and four conserved PLD signature domains. The PLD PH domain is specific for bisphosphorylated inositides. PH domains have diverse functions, but in general are involved in targeting proteins to the appropriate cellular location or in the interaction with a binding partner. They share little sequence conservation, but all have a common fold, which is electrostatically polarized. Less than 10% of PH domains bind phosphoinositide phosphates (PIPs) with high affinity and specificity. PH domains are distinguished from other PIP-binding domains by their specific high-affinity binding to PIPs with two vicinal phosphate groups: PtdIns(3,4)P2, PtdIns(4,5)P2 or PtdIns(3,4,5)P3 which results in targeting some PH domain proteins to the plasma membrane. A few display strong specificity in lipid binding. Any specificity is usually determined by loop regions or insertions in the N-terminus of the domain, which are not conserved across all PH domains. PH domains are found in cellular signaling proteins such as serine/threonine kinase, tyrosine kinases, regulators of G-proteins, endocytotic GTPases, adaptors, as well as cytoskeletal associated molecules and in lipid associated enzymes.


Pssm-ID: 269956  Cd Length: 136  Bit Score: 38.40  E-value: 1.57e-03
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 115527076 110 KQGYLEKKSKDHS-------------FFGSEWQKRWCVVSRGLFYYYANEKSKQPKGTFLI-KGYGVRMAPHLRRDSKKE 175
Cdd:cd01254   26 KEGYLKKRSGGHRqgwrvchfyccckAMCGRWSKRWFIVKDSFLAYVKDPDSGAILDVFLFdQEFKVSRGGKETKYGSRH 105
                         90       100       110
                 ....*....|....*....|....*....|
gi 115527076 176 ScFELTSQDRRsYEFTATSPAEARDWVDQI 205
Cdd:cd01254  106 G-LKITNLSRK-LKLKCKSERKAKQWVESI 133
SH3_Intersectin1_3 cd11991
Third Src homology 3 domain (or SH3C) of Intersectin-1; Intersectin-1 (ITSN1) is an adaptor ...
298-349 1.82e-03

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


Pssm-ID: 212924  Cd Length: 52  Bit Score: 36.11  E-value: 1.82e-03
                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|..
gi 115527076 298 YQGLWDCHGDQPDELSFQRGDLIRILSKEYNmygWWVGELNSLVGIVPKEYL 349
Cdd:cd11991    2 YVAMYTYESNEQGDLTFQQGDVILVTKKDGD---WWTGTVGDKTGVFPSNYV 50
SH3_Intersectin2_2 cd11990
Second Src homology 3 domain (or SH3B) of Intersectin-2; Intersectin-2 (ITSN2) is an adaptor ...
302-350 1.99e-03

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


Pssm-ID: 212923 [Multi-domain]  Cd Length: 52  Bit Score: 35.79  E-value: 1.99e-03
                         10        20        30        40
                 ....*....|....*....|....*....|....*....|....*....
gi 115527076 302 WDCHGDqpDELSFQRGDLIRILSKEYNmygWWVGELNSLVGIVPKEYLT 350
Cdd:cd11990    8 WTAKKD--NHLNFSKNDIITVLEQQEN---WWFGEVHGGRGWFPKSYVK 51
SH3_PRMT2 cd11806
Src homology 3 domain of Protein arginine N-methyltransferase 2; PRMT2, also called HRMT1L1, ...
310-351 2.06e-03

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


Pssm-ID: 212740 [Multi-domain]  Cd Length: 53  Bit Score: 35.83  E-value: 2.06e-03
                         10        20        30        40
                 ....*....|....*....|....*....|....*....|..
gi 115527076 310 DELSFQRGDLIRILSKEYNmyGWWVGELNSLVGIVPKEYLTT 351
Cdd:cd11806   14 SQLSFESGDKLLVLRKPSV--DWWWAEHNGCCGYIPASHLHQ 53
SH3_CD2AP-like_2 cd11874
Second Src Homology 3 domain (SH3B) of CD2-associated protein and similar proteins; This ...
308-345 2.14e-03

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


Pssm-ID: 212807 [Multi-domain]  Cd Length: 53  Bit Score: 35.77  E-value: 2.14e-03
                         10        20        30
                 ....*....|....*....|....*....|....*...
gi 115527076 308 QPDELSFQRGDLIRILSKEYNmyGWWVGELNSLVGIVP 345
Cdd:cd11874   12 NEDELELKVGDTIEVLGEVEE--GWWEGKLNGKVGVFP 47
SH3_RIM-BP_2 cd12012
Second Src homology 3 domain of Rab3-interacting molecules (RIMs) binding proteins; RIMs ...
310-345 2.24e-03

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


Pssm-ID: 212945  Cd Length: 62  Bit Score: 36.12  E-value: 2.24e-03
                         10        20        30
                 ....*....|....*....|....*....|....*.
gi 115527076 310 DELSFQRGDLIRILSkEYNMYGWWVGELNSLVGIVP 345
Cdd:cd12012   22 EELPFKEGQLIKVYG-DKDADGFYLGEINGRRGLVP 56
SH3_DNMBP_C2_like cd11800
Second C-terminal Src homology 3 domain of Dynamin Binding Protein, also called Tuba, and ...
297-349 2.34e-03

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


Pssm-ID: 212734 [Multi-domain]  Cd Length: 57  Bit Score: 35.81  E-value: 2.34e-03
                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|....*.
gi 115527076 297 YYQGLWDCHGDQPDELSFQRGDLIRILSKeYNMYG---WWVGELNSLVGIVPKEYL 349
Cdd:cd11800    1 YYYALYTFEARSPGELSVTEGQVVTVLEK-HDLKGnpeWWLVEDRGKQGYVPSNYL 55
PH_TBC1D2A cd01265
TBC1 domain family member 2A pleckstrin homology (PH) domain; TBC1D2A (also called PARIS-1 ...
112-204 2.45e-03

TBC1 domain family member 2A pleckstrin homology (PH) domain; TBC1D2A (also called PARIS-1/Prostate antigen recognized and identified by SEREX 1 and ARMUS) contains a PH domain and a TBC-type GTPase catalytic domain. TBC1D2A integrates signaling between Arf6, Rac1, and Rab7 during junction disassembly. Activated Rac1 recruits TBC1D2A to locally inactivate Rab7 via its C-terminal TBC/RabGAP domain and facilitate E-cadherin degradation in lysosomes. The TBC1D2A PH domain mediates localization at cell-cell contacts and coprecipitates with cadherin complexes. PH domains have diverse functions, but in general are involved in targeting proteins to the appropriate cellular location or in the interaction with a binding partner. They share little sequence conservation, but all have a common fold, which is electrostatically polarized. Less than 10% of PH domains bind phosphoinositide phosphates (PIPs) with high affinity and specificity. PH domains are distinguished from other PIP-binding domains by their specific high-affinity binding to PIPs with two vicinal phosphate groups: PtdIns(3,4)P2, PtdIns(4,5)P2 or PtdIns(3,4,5)P3 which results in targeting some PH domain proteins to the plasma membrane. A few display strong specificity in lipid binding. Any specificity is usually determined by loop regions or insertions in the N-terminus of the domain, which are not conserved across all PH domains. PH domains are found in cellular signaling proteins such as serine/threonine kinase, tyrosine kinases, regulators of G-proteins, endocytotic GTPases, adaptors, as well as cytoskeletal associated molecules and in lipid associated enzymes.


Pssm-ID: 269966  Cd Length: 102  Bit Score: 36.92  E-value: 2.45e-03
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 115527076 112 GYLEKKSKdHSFFGSEWQKRWCVV--SRGLFYYYANEKSKQPKGTFLIKGYGVRMAPhlrrdSKKESCFELTSQDrRSYE 189
Cdd:cd01265    4 GYLNKLET-RGLGLKGWKRRWFVLdeSKCQLYYYRSPQDATPLGSIDLSGAAFSYDP-----EAEPGQFEIHTPG-RVHI 76
                         90
                 ....*....|....*
gi 115527076 190 FTATSPAEARDWVDQ 204
Cdd:cd01265   77 LKASTRQAMLYWLQA 91
SH3_alphaPIX cd12060
Src Homology 3 domain of alpha-Pak Interactive eXchange factor; Alpha-PIX, also called Rho ...
310-349 3.14e-03

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


Pssm-ID: 212993  Cd Length: 58  Bit Score: 35.75  E-value: 3.14e-03
                         10        20        30        40
                 ....*....|....*....|....*....|....*....|
gi 115527076 310 DELSFQRGDLIRILSKEYNmyGWWVGELNSLVGIVPKEYL 349
Cdd:cd12060   16 DELSVCKGDIIYVTRVEEG--GWWEGTLNGKTGWFPSNYV 53
SH3_ARHGAP32_33 cd11835
Src homology 3 domain of Rho GTPase-activating proteins 32 and 33, and similar proteins; ...
305-347 3.38e-03

Src homology 3 domain of Rho GTPase-activating proteins 32 and 33, and similar proteins; Members of this family contain N-terminal PX and Src Homology 3 (SH3) domains, a central Rho GAP domain, and C-terminal extensions. RhoGAPs (or ARHGAPs) bind to Rho proteins and enhance the hydrolysis rates of bound GTP. ARHGAP32 is also called RICS, PX-RICS, p250GAP, or p200RhoGAP. It is a Rho GTPase-activating protein for Cdc42 and Rac1, and is implicated in the regulation of postsynaptic signaling and neurite outgrowth. PX-RICS, a variant of RICS that contain PX and SH3 domains, is the main isoform expressed during neural development. It is involved in neural functions including axon and dendrite extension, postnatal remodeling, and fine-tuning of neural circuits during early brain development. ARHGAP33, also called sorting nexin 26 or TCGAP (Tc10/CDC42 GTPase-activating protein), is widely expressed in the brain where it is involved in regulating the outgrowth of axons and dendrites and is regulated by the protein tyrosine kinase Fyn. It is translocated to the plasma membrane in adipocytes in response to insulin and may be involved in the regulation of insulin-stimulated glucose transport. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 212769 [Multi-domain]  Cd Length: 54  Bit Score: 35.50  E-value: 3.38e-03
                         10        20        30        40
                 ....*....|....*....|....*....|....*....|....*.
gi 115527076 305 HGDQPDELSFQRGDLIRIL---SKEYNMygWWVGELNSLVGIVPKE 347
Cdd:cd11835    9 TAQAPDELSLEVGDIVSVIdmpPPEEST--WWRGKKGFQVGFFPSE 52
SH3_MPP cd11862
Src Homology 3 domain of Membrane Protein, Palmitoylated (or MAGUK p55 subfamily member) ...
312-345 3.54e-03

Src Homology 3 domain of Membrane Protein, Palmitoylated (or MAGUK p55 subfamily member) proteins; The MPP/p55 subfamily of MAGUK (membrane-associated guanylate kinase) proteins includes at least eight vertebrate members (MPP1-7 and CASK), four Drosophila proteins (Stardust, Varicose, CASK and Skiff), and other similar proteins; they all contain one each of the core of three domains characteristic of MAGUK proteins: PDZ, SH3, and guanylate kinase (GuK). In addition, most members except for MPP1 contain N-terminal L27 domains and some also contain a Hook (Protein 4.1 Binding) motif in between the SH3 and GuK domains. CASK has an additional calmodulin-dependent kinase (CaMK)-like domain at the N-terminus. Members of this subfamily are scaffolding proteins that play important roles in regulating and establishing cell polarity, cell adhesion, and synaptic targeting and transmission, among others. The GuK domain in MAGUK proteins is enzymatically inactive; instead, the domain mediates protein-protein interactions and associates intramolecularly with the SH3 domain. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 212796  Cd Length: 61  Bit Score: 35.25  E-value: 3.54e-03
                         10        20        30
                 ....*....|....*....|....*....|....*...
gi 115527076 312 LSFQRGDLIRILSKEyNMYgWW----VGELNSLVGIVP 345
Cdd:cd11862   23 LSFKKGDILQIVNQD-DPN-WWqarkVGDPNGRAGLIP 58
PH_ARHGAP9-like cd13233
Beta-spectrin pleckstrin homology (PH) domain; ARHGAP family genes encode Rho/Rac/Cdc42-like ...
109-206 3.75e-03

Beta-spectrin pleckstrin homology (PH) domain; ARHGAP family genes encode Rho/Rac/Cdc42-like GTPase activating proteins with RhoGAP domain. The ARHGAP members here all have a PH domain upstream of their C-terminal RhoGAP domain. Some have additional N-terminal SH3 and WW domains. The members here include: ARHGAP9, ARHGAP12, ARHGAP15, and ARHGAP27. ARHGAP27 and ARHGAP12 shared the common-domain structure, consisting of SH3, WW, PH, and RhoGAP domains. The PH domain of ArhGAP9 employs a non-canonical phosphoinositide binding mechanism, a variation of the spectrin- Ins(4,5)P2-binding mode, that gives rise to a unique PI binding profile, namely a preference for both PI(4,5)P2 and the PI 3-kinase products PI(3,4,5)P3 and PI(3,4)P2. This lipid binding mechanism is also employed by the PH domain of Tiam1 and Slm1. PH domains have diverse functions, but in general are involved in targeting proteins to the appropriate cellular location or in the interaction with a binding partner. They share little sequence conservation, but all have a common fold, which is electrostatically polarized. Less than 10% of PH domains bind phosphoinositide phosphates (PIPs) with high affinity and specificity. PH domains are distinguished from other PIP-binding domains by their specific high-affinity binding to PIPs with two vicinal phosphate groups: PtdIns(3,4)P2, PtdIns(4,5)P2 or PtdIns(3,4,5)P3 which results in targeting some PH domain proteins to the plasma membrane. A few display strong specificity in lipid binding. Any specificity is usually determined by loop regions or insertions in the N-terminus of the domain, which are not conserved across all PH domains. PH domains are found in cellular signaling proteins such as serine/threonine kinase, tyrosine kinases, regulators of G-proteins, endocytotic GTPases, adaptors, as well as cytoskeletal associated molecules and in lipid associated enzymes.


Pssm-ID: 270053  Cd Length: 110  Bit Score: 36.49  E-value: 3.75e-03
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 115527076 109 IKQGYLE--------KKSKDHsffgseWQKRWCVVSRGLFYYYANEKSKQ--------PKGTFLIKGYGVRMAPHLrrdS 172
Cdd:cd13233    1 EKQGLLNktkiaengKKLRKN------WSTSWVVLTSSHLLFYKDAKSAAksgnpyskPESSVDLRGASIEWAKEK---S 71
                         90       100       110
                 ....*....|....*....|....*....|....
gi 115527076 173 KKESCFELTSQDRRSYEFTATSPAEARDWVDQIS 206
Cdd:cd13233   72 SRKNVFQISTVTGTEFLLQSDNDTEIREWFDAIK 105
SH3_Nck1_2 cd11901
Second Src Homology 3 domain of Nck1 adaptor protein; Nck1 (also called Nckalpha) plays a ...
306-350 3.92e-03

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


Pssm-ID: 212834 [Multi-domain]  Cd Length: 55  Bit Score: 35.40  E-value: 3.92e-03
                         10        20        30        40
                 ....*....|....*....|....*....|....*....|....*
gi 115527076 306 GDQPDELSFQRGDLIRILSKEYNmyGWWVGELNSLVGIVPKEYLT 350
Cdd:cd11901   12 AEREDELSLVKGTKVIVMEKCSD--GWWRGSYNGQVGWFPSNYVT 54
SH3_SH3RF3_1 cd11928
First Src Homology 3 domain of SH3 domain containing ring finger 3, an E3 ubiquitin-protein ...
297-349 4.79e-03

First Src Homology 3 domain of SH3 domain containing ring finger 3, an E3 ubiquitin-protein ligase; SH3RF3 is also called POSH2 (Plenty of SH3s 2) or SH3MD4 (SH3 multiple domains protein 4). It is a scaffold protein with E3 ubiquitin-protein ligase activity. It was identified in the screen for interacting partners of p21-activated kinase 2 (PAK2). It may play a role in regulating JNK mediated apoptosis in certain conditions. It also interacts with GTP-loaded Rac1. SH3RF3 is highly homologous to SH3RF1; it also contains an N-terminal RING finger domain and four SH3 domains. This model represents the first SH3 domain, located at the N-terminal half, of SH3RF3. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 212861  Cd Length: 54  Bit Score: 34.90  E-value: 4.79e-03
                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|...
gi 115527076 297 YYQGLWDCHGDQPDELSFQRGDLIrILSKEYNMyGWWVGELNSLVGIVPKEYL 349
Cdd:cd11928    2 CGKALYSYEGKEPGDLKFNKGDII-ILRRKVDE-NWYHGELNGCHGFLPASYI 52
SH3_RIM-BP_3 cd12013
Third Src homology 3 domain of Rab3-interacting molecules (RIMs) binding proteins; RIMs ...
311-350 5.16e-03

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


Pssm-ID: 212946  Cd Length: 61  Bit Score: 35.05  E-value: 5.16e-03
                         10        20        30        40
                 ....*....|....*....|....*....|....*....|
gi 115527076 311 ELSFQRGDLIRILSkEYNMYGWWVGELNSLVGIVPKEYLT 350
Cdd:cd12013   22 ELSFRAGDIITVFG-EMDEDGFYYGELNGQRGLVPSNFLE 60
SH3_CIN85_1 cd12052
First Src Homology 3 domain (SH3A) of Cbl-interacting protein of 85 kDa; CIN85, also called ...
302-349 7.15e-03

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


Pssm-ID: 212985 [Multi-domain]  Cd Length: 53  Bit Score: 34.48  E-value: 7.15e-03
                         10        20        30        40
                 ....*....|....*....|....*....|....*....|....*...
gi 115527076 302 WDCHGDQPDELSFQRGDLIRILSKEYNmyGWWVGELNSLVGIVPKEYL 349
Cdd:cd12052    6 FDYKAQHEDELTITVGDIITKIKKDDG--GWWEGEIKGRRGLFPDNFV 51
SH3_GAS7 cd11829
Src homology 3 domain of Growth Arrest Specific protein 7; GAS7 is mainly expressed in the ...
299-349 8.03e-03

Src homology 3 domain of Growth Arrest Specific protein 7; GAS7 is mainly expressed in the brain and is required for neurite outgrowth. It may also play a role in the protection and migration of embryonic stem cells. Treatment-related acute myeloid leukemia (AML) has been reported resulting from mixed-lineage leukemia (MLL)-GAS7 translocations as a complication of primary cancer treatment. GAS7 contains an N-terminal SH3 domain, followed by a WW domain, and a central F-BAR domain. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 212763 [Multi-domain]  Cd Length: 52  Bit Score: 34.41  E-value: 8.03e-03
                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|..
gi 115527076 299 QGLWDCHGDQPDE-LSFQRGDLIRILSKEYNmyGWWVGELNSLVGIVPKEYL 349
Cdd:cd11829    3 RTLYAFTGEQHQQgLSFEAGELIRVLQAPDG--GWWEGEKDGLRGWFPASYV 52
SH3_RUSC2 cd11957
Src homology 3 domain of RUN and SH3 domain-containing protein 2; RUSC2, also called Iporin or ...
304-350 8.39e-03

Src homology 3 domain of RUN and SH3 domain-containing protein 2; RUSC2, also called Iporin or Interacting protein of Rab1, is expressed ubiquitously with highest amounts in the brain and testis. It interacts with the small GTPase Rab1 and the Golgi matrix protein GM130, and may function in linking GTPases to certain intracellular signaling pathways. RUSC proteins are adaptor proteins consisting of RUN, leucine zipper, and SH3 domains. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 212890  Cd Length: 52  Bit Score: 34.12  E-value: 8.39e-03
                         10        20        30        40
                 ....*....|....*....|....*....|....*....|....*....
gi 115527076 304 CH--GDQPDELSFQRGDLIRILSKEYNmyGWWVGELNSLVGIVPKEYLT 350
Cdd:cd11957    6 CHhiATEPGQLSFNKGDILQVLSRADG--DWLRCSLGPDSGLVPIAYVT 52
PH_Sbf1_hMTMR5 cd01235
Set binding factor 1 (also called Human MTMR5) Pleckstrin Homology (PH) domain; Sbf1 is a ...
128-210 9.12e-03

Set binding factor 1 (also called Human MTMR5) Pleckstrin Homology (PH) domain; Sbf1 is a myotubularin-related pseudo-phosphatase. Both Sbf1 and myotubularin interact with the SET domains of Hrx and other epigenetic regulatory proteins, but Sbf1 lacks phosphatase activity due to several amino acid changes in its structurally preserved catalytic pocket. It contains pleckstrin (PH), GEF, and myotubularin homology domains that are thought to be responsible for signaling and growth control. Sbf1 functions as an inhibitor of cellular growth. The N-terminal GEF homology domain serves to inhibit the transforming effects of Sbf1. PH domains have diverse functions, but in general are involved in targeting proteins to the appropriate cellular location or in the interaction with a binding partner. They share little sequence conservation, but all have a common fold, which is electrostatically polarized. Less than 10% of PH domains bind phosphoinositide phosphates (PIPs) with high affinity and specificity. PH domains are distinguished from other PIP-binding domains by their specific high-affinity binding to PIPs with two vicinal phosphate groups: PtdIns(3,4)P2, PtdIns(4,5)P2 or PtdIns(3,4,5)P3 which results in targeting some PH domain proteins to the plasma membrane. A few display strong specificity in lipid binding. Any specificity is usually determined by loop regions or insertions in the N-terminus of the domain, which are not conserved across all PH domains. PH domains are found in cellular signaling proteins such as serine/threonine kinase, tyrosine kinases, regulators of G-proteins, endocytotic GTPases, adaptors, as well as cytoskeletal associated molecules and in lipid associated enzymes.


Pssm-ID: 269941  Cd Length: 106  Bit Score: 35.38  E-value: 9.12e-03
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 115527076 128 WQKRWCV--VSRGLFYYYANEKSKQPKGTF-LIKGYGVRMA----PHLRRDSKKeSCFELTSqDRRSYEFTATSPAEARD 200
Cdd:cd01235   19 WKQRWFVldSTKHQLRYYESREDTKCKGFIdLAEVESVTPAtpiiGAPKRADEG-AFFDLKT-NKRVYNFCAFDAESAQQ 96
                         90
                 ....*....|
gi 115527076 201 WVDQISFLLK 210
Cdd:cd01235   97 WIEKIQSCLS 106
SH3_Sho1p cd11855
Src homology 3 domain of High osmolarity signaling protein Sho1p; Sho1p (or Sho1), also called ...
302-349 9.96e-03

Src homology 3 domain of High osmolarity signaling protein Sho1p; Sho1p (or Sho1), also called SSU81 (Suppressor of SUA8-1 mutation), is a yeast membrane protein that regulates adaptation to high salt conditions by activating the HOG (high-osmolarity glycerol) pathway. High salt concentrations lead to the localization to the membrane of the MAPKK Pbs2, which is then activated by the MAPKK Ste11 and in turn, activates the MAPK Hog1. Pbs2 is localized to the membrane though the interaction of its PxxP motif with the SH3 domain of Sho1p. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 212789 [Multi-domain]  Cd Length: 55  Bit Score: 33.93  E-value: 9.96e-03
                         10        20        30        40
                 ....*....|....*....|....*....|....*....|....*....
gi 115527076 302 WDCHGDQPDELSFQRGDLIRILSKEYNmygWWVGEL-NSLVGIVPKEYL 349
Cdd:cd11855    8 YDASPDDPNELSFEKGEILEVSDTSGK---WWQARKsNGETGICPSNYL 53
 
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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