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Conserved domains on  [gi|409264659|ref|NP_001258524|]
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epidermal growth factor receptor kinase substrate 8 isoform 1 [Mus musculus]

Protein Classification

epidermal growth factor receptor kinase substrate 8 family protein( domain architecture ID 10100538)

epidermal growth factor receptor kinase substrate 8 (EPS8) family protein similar to human EPS8, a signaling adapter that controls various cellular protrusions by regulating actin cytoskeleton dynamics and architecture

Graphical summary

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List of domain hits

Name Accession Description Interval E-value
PTB_EPS8 cd01210
Epidermal growth factor receptor kinase substrate (EPS8)-like Phosphotyrosine-binding (PTB) ...
64-191 1.88e-68

Epidermal growth factor receptor kinase substrate (EPS8)-like Phosphotyrosine-binding (PTB) domain; EPS8 is a regulator of Rac signaling. It consists of a PTB and an SH3 domain. PTB domains have a common PH-like fold and are found in various eukaryotic signaling molecules. This domain was initially shown to binds peptides with a NPXY motif with differing requirements for phosphorylation of the tyrosine, although more recent studies have found that some types of PTB domains can bind to peptides lack tyrosine residues altogether. In contrast to SH2 domains, which recognize phosphotyrosine and adjacent carboxy-terminal residues, PTB-domain binding specificity is conferred by residues amino-terminal to the phosphotyrosine. PTB domains are classified into three groups: phosphotyrosine-dependent Shc-like, phosphotyrosine-dependent IRS-like, and phosphotyrosine-independent Dab-like PTB domains. This cd is part of the Dab-like subgroup.


:

Pssm-ID: 269921  Cd Length: 131  Bit Score: 222.04  E-value: 1.88e-68
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 409264659  64 QYRVEHLTTFVLDRKDAMITVEDGIRKLKLLDAKGKVWTQDMILQVDDRAVSLIDLESKNELENFPLNTISHCQAVVHAC 143
Cdd:cd01210    4 QYRVEHLATFTLGREEGVQTVEDALRKLKELDAKGRIWSQEMLLQVNDGWVLLLDIETKEELESFPLSSIQECTAVLSTC 83
                         90       100       110       120
                 ....*....|....*....|....*....|....*....|....*...
gi 409264659 144 SYDSILALVCKEPTQSKPDLHLFQCDEVKANLISEDIESAISDSKGGK 191
Cdd:cd01210   84 SYNSILLLVVQEPDQPKPEMHLFQCDEVGAELLVEDLQKALSGKRSGR 131
SAM_EPS8-like cd09540
SAM domain of EPS8-like subfamily; SAM (sterile alpha motif) domain of EPS8-like subfamily is ...
719-783 5.58e-37

SAM domain of EPS8-like subfamily; SAM (sterile alpha motif) domain of EPS8-like subfamily is a putative protein-protein interaction domain. This subfamily includes epidermal growth factor receptor kinase substrate 8 proteins (EPS8) and epidermal growth factor receptor kinase substrate 8-like (EPSL8) 1, 2, 3 proteins with the SAM domain located in the C-terminal effector region. This region is responsible for intracellular protein localization and is involved in small GTPases (such as Rac and Rab5) activation/inhibition. Proteins belonging to this group participate in coordination and integration of multiple signaling pathways; in particular, they play a role in the control of actin dynamics and in receptor endocytosis. They can form complexes with other proteins; for example, in the actin signaling network they interact with SOS1 and E3b1 (Abl1) proteins as well as with CRIB (via SH3 domains) during the actin filament formation, and in the receptor endocytosis their partner is RN-tre protein.


:

Pssm-ID: 188939  Cd Length: 66  Bit Score: 132.84  E-value: 5.58e-37
                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 409264659 719 NITYDSSPEEVKTWLQSKGFNPVTVNSLGVLNGAQLFSLNKDELRSVCP-EGARVFNQITVQKAAL 783
Cdd:cd09540    1 PLTYDSSPEEVKAWLQAKGFSKITVRSLGVLTGAQLFSLNKEELKTVCPeEGARVYSQLTVQKSAL 66
SH3_Eps8 cd11764
Src Homology 3 domain of Epidermal growth factor receptor kinase substrate 8 and similar ...
534-587 8.05e-29

Src Homology 3 domain of Epidermal growth factor receptor kinase substrate 8 and similar proteins; This group is composed of Eps8 and Eps8-like proteins including Eps8-like 1-3, among others. These proteins contain N-terminal Phosphotyrosine-binding (PTB), central SH3, and C-terminal effector domains. Eps8 binds either Abi1 (also called E3b1) or Rab5 GTPase activating protein RN-tre through its SH3 domain. With Abi1 and Sos1, it becomes part of a trimeric complex that is required to activate Rac. Together with RN-tre, it inhibits the internalization of EGFR. The SH3 domains of Eps8 and similar proteins recognize peptides containing a PxxDY motif, instead of the classical PxxP motif. SH3 domains are protein interaction domains that usually bind to proline-rich ligands with moderate affinity and selectivity. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


:

Pssm-ID: 212698 [Multi-domain]  Cd Length: 54  Bit Score: 108.89  E-value: 8.05e-29
                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|....
gi 409264659 534 YAKSKYDFVARNSSELSVMKDDVLEILDDRRQWWKVRNASGDSGFVPNNILDIM 587
Cdd:cd11764    1 YVRVLYDFTARNSKELSVLKGEYLEVLDDSRQWWKVRNSRGQVGYVPHNILEPY 54
 
Name Accession Description Interval E-value
PTB_EPS8 cd01210
Epidermal growth factor receptor kinase substrate (EPS8)-like Phosphotyrosine-binding (PTB) ...
64-191 1.88e-68

Epidermal growth factor receptor kinase substrate (EPS8)-like Phosphotyrosine-binding (PTB) domain; EPS8 is a regulator of Rac signaling. It consists of a PTB and an SH3 domain. PTB domains have a common PH-like fold and are found in various eukaryotic signaling molecules. This domain was initially shown to binds peptides with a NPXY motif with differing requirements for phosphorylation of the tyrosine, although more recent studies have found that some types of PTB domains can bind to peptides lack tyrosine residues altogether. In contrast to SH2 domains, which recognize phosphotyrosine and adjacent carboxy-terminal residues, PTB-domain binding specificity is conferred by residues amino-terminal to the phosphotyrosine. PTB domains are classified into three groups: phosphotyrosine-dependent Shc-like, phosphotyrosine-dependent IRS-like, and phosphotyrosine-independent Dab-like PTB domains. This cd is part of the Dab-like subgroup.


Pssm-ID: 269921  Cd Length: 131  Bit Score: 222.04  E-value: 1.88e-68
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 409264659  64 QYRVEHLTTFVLDRKDAMITVEDGIRKLKLLDAKGKVWTQDMILQVDDRAVSLIDLESKNELENFPLNTISHCQAVVHAC 143
Cdd:cd01210    4 QYRVEHLATFTLGREEGVQTVEDALRKLKELDAKGRIWSQEMLLQVNDGWVLLLDIETKEELESFPLSSIQECTAVLSTC 83
                         90       100       110       120
                 ....*....|....*....|....*....|....*....|....*...
gi 409264659 144 SYDSILALVCKEPTQSKPDLHLFQCDEVKANLISEDIESAISDSKGGK 191
Cdd:cd01210   84 SYNSILLLVVQEPDQPKPEMHLFQCDEVGAELLVEDLQKALSGKRSGR 131
PTB pfam08416
Phosphotyrosine-binding domain; The phosphotyrosine-binding domain (PTB, also ...
64-194 7.75e-68

Phosphotyrosine-binding domain; The phosphotyrosine-binding domain (PTB, also phosphotyrosine-interaction or PI domain) in the protein tensin tends to be found at the C-terminus. Tensin is a multi-domain protein that binds to actin filaments and functions as a focal-adhesion molecule (focal adhesions are regions of plasma membrane through which cells attach to the extracellular matrix). Human tensin has actin-binding sites, an SH2 (pfam00017) domain and a region similar to the tumour suppressor PTEN. The PTB domain interacts with the cytoplasmic tails of beta integrin by binding to an NPXY motif.


Pssm-ID: 429984  Cd Length: 131  Bit Score: 220.68  E-value: 7.75e-68
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 409264659   64 QYRVEHLTTFVLDRKDAMITVEDGIRKLKLLDAKGKVWTQDMILQVDDRAVSLIDLESKNELENFPLNTISHCQAVVHAC 143
Cdd:pfam08416   1 QYRVEHLTTFELDSLTGLQAVEDAIRKLQLLDAQGRVWTQEMLLQVSDQGITLTDNETKEELESYPLDSISHCQAVLNDG 80
                          90       100       110       120       130
                  ....*....|....*....|....*....|....*....|....*....|.
gi 409264659  144 SYDSILALVCKEPTQSKPDLHLFQCDEVKANLISEDIESAISDSKGGKQKR 194
Cdd:pfam08416  81 RYNSILALVCQEPGQSKPDVHLFQCDELGAELIAEDIESALSDVRLGKPKK 131
SAM_EPS8-like cd09540
SAM domain of EPS8-like subfamily; SAM (sterile alpha motif) domain of EPS8-like subfamily is ...
719-783 5.58e-37

SAM domain of EPS8-like subfamily; SAM (sterile alpha motif) domain of EPS8-like subfamily is a putative protein-protein interaction domain. This subfamily includes epidermal growth factor receptor kinase substrate 8 proteins (EPS8) and epidermal growth factor receptor kinase substrate 8-like (EPSL8) 1, 2, 3 proteins with the SAM domain located in the C-terminal effector region. This region is responsible for intracellular protein localization and is involved in small GTPases (such as Rac and Rab5) activation/inhibition. Proteins belonging to this group participate in coordination and integration of multiple signaling pathways; in particular, they play a role in the control of actin dynamics and in receptor endocytosis. They can form complexes with other proteins; for example, in the actin signaling network they interact with SOS1 and E3b1 (Abl1) proteins as well as with CRIB (via SH3 domains) during the actin filament formation, and in the receptor endocytosis their partner is RN-tre protein.


Pssm-ID: 188939  Cd Length: 66  Bit Score: 132.84  E-value: 5.58e-37
                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 409264659 719 NITYDSSPEEVKTWLQSKGFNPVTVNSLGVLNGAQLFSLNKDELRSVCP-EGARVFNQITVQKAAL 783
Cdd:cd09540    1 PLTYDSSPEEVKAWLQAKGFSKITVRSLGVLTGAQLFSLNKEELKTVCPeEGARVYSQLTVQKSAL 66
SH3_Eps8 cd11764
Src Homology 3 domain of Epidermal growth factor receptor kinase substrate 8 and similar ...
534-587 8.05e-29

Src Homology 3 domain of Epidermal growth factor receptor kinase substrate 8 and similar proteins; This group is composed of Eps8 and Eps8-like proteins including Eps8-like 1-3, among others. These proteins contain N-terminal Phosphotyrosine-binding (PTB), central SH3, and C-terminal effector domains. Eps8 binds either Abi1 (also called E3b1) or Rab5 GTPase activating protein RN-tre through its SH3 domain. With Abi1 and Sos1, it becomes part of a trimeric complex that is required to activate Rac. Together with RN-tre, it inhibits the internalization of EGFR. The SH3 domains of Eps8 and similar proteins recognize peptides containing a PxxDY motif, instead of the classical PxxP motif. SH3 domains are protein interaction domains that usually bind to proline-rich ligands with moderate affinity and selectivity. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 212698 [Multi-domain]  Cd Length: 54  Bit Score: 108.89  E-value: 8.05e-29
                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|....
gi 409264659 534 YAKSKYDFVARNSSELSVMKDDVLEILDDRRQWWKVRNASGDSGFVPNNILDIM 587
Cdd:cd11764    1 YVRVLYDFTARNSKELSVLKGEYLEVLDDSRQWWKVRNSRGQVGYVPHNILEPY 54
PTB smart00462
Phosphotyrosine-binding domain, phosphotyrosine-interaction (PI) domain; PTB/PI domain ...
64-197 7.52e-26

Phosphotyrosine-binding domain, phosphotyrosine-interaction (PI) domain; PTB/PI domain structure similar to those of pleckstrin homology (PH) and IRS-1-like PTB domains.


Pssm-ID: 214675  Cd Length: 134  Bit Score: 103.55  E-value: 7.52e-26
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 409264659    64 QYRVEHLTTFVLDRKDAMITVEDGIRKLKLLDAKGKVWTQDMILQVDDRAVSLIDLESKNELENFPLNTISHCQAVVHac 143
Cdd:smart00462   5 SFRVKYLGSVEVPEARGLQVVQEAIRKLRAAQGSEKKEPQKVILSISSRGVKLIDEDTKAVLHEHPLRRISFCAVGPD-- 82
                           90       100       110       120       130
                   ....*....|....*....|....*....|....*....|....*....|....
gi 409264659   144 sYDSILALVCKEPTQSKPDLHLFQCDEVkANLISEDIESAISDSKGGKQKRRPE 197
Cdd:smart00462  83 -DLDVFGYIARDPGSSRFACHVFRCEKA-AEDIALAIGQAFQLAYELKLKARSE 134
SAM_3 pfam18016
SAM domain (Sterile alpha motif);
718-777 9.44e-21

SAM domain (Sterile alpha motif);


Pssm-ID: 436214  Cd Length: 65  Bit Score: 86.55  E-value: 9.44e-21
                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|..
gi 409264659  718 INITYDSSPEEVKTWLQSKGFNPVTVNSLGVLNGAQLFSLNKDELRSVCP--EGARVFNQIT 777
Cdd:pfam18016   4 INITPKSTPEEVQAWLTAKGFSKKTVKSLGTLSGAQLFSLSKEELKQICGpaEGIRLYSQLL 65
SH3 smart00326
Src homology 3 domains; Src homology 3 (SH3) domains bind to target proteins through sequences ...
531-584 5.87e-13

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: 64.10  E-value: 5.87e-13
                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....*
gi 409264659   531 PKKYAKSKYDFVARNSSELSVMKDDVLEILDDRRQ-WWKVRNASGDSGFVPNNIL 584
Cdd:smart00326   1 EGPQVRALYDYTAQDPDELSFKKGDIITVLEKSDDgWWKGRLGRGKEGLFPSNYV 55
SH3_1 pfam00018
SH3 domain; SH3 (Src homology 3) domains are often indicative of a protein involved in signal ...
536-580 2.16e-10

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: 56.44  E-value: 2.16e-10
                          10        20        30        40
                  ....*....|....*....|....*....|....*....|....*.
gi 409264659  536 KSKYDFVARNSSELSVMKDDVLEILDD-RRQWWKVRNASGDSGFVP 580
Cdd:pfam00018   1 VALYDYTAQEPDELSFKKGDIIIVLEKsEDGWWKGRNKGGKEGLIP 46
 
Name Accession Description Interval E-value
PTB_EPS8 cd01210
Epidermal growth factor receptor kinase substrate (EPS8)-like Phosphotyrosine-binding (PTB) ...
64-191 1.88e-68

Epidermal growth factor receptor kinase substrate (EPS8)-like Phosphotyrosine-binding (PTB) domain; EPS8 is a regulator of Rac signaling. It consists of a PTB and an SH3 domain. PTB domains have a common PH-like fold and are found in various eukaryotic signaling molecules. This domain was initially shown to binds peptides with a NPXY motif with differing requirements for phosphorylation of the tyrosine, although more recent studies have found that some types of PTB domains can bind to peptides lack tyrosine residues altogether. In contrast to SH2 domains, which recognize phosphotyrosine and adjacent carboxy-terminal residues, PTB-domain binding specificity is conferred by residues amino-terminal to the phosphotyrosine. PTB domains are classified into three groups: phosphotyrosine-dependent Shc-like, phosphotyrosine-dependent IRS-like, and phosphotyrosine-independent Dab-like PTB domains. This cd is part of the Dab-like subgroup.


Pssm-ID: 269921  Cd Length: 131  Bit Score: 222.04  E-value: 1.88e-68
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 409264659  64 QYRVEHLTTFVLDRKDAMITVEDGIRKLKLLDAKGKVWTQDMILQVDDRAVSLIDLESKNELENFPLNTISHCQAVVHAC 143
Cdd:cd01210    4 QYRVEHLATFTLGREEGVQTVEDALRKLKELDAKGRIWSQEMLLQVNDGWVLLLDIETKEELESFPLSSIQECTAVLSTC 83
                         90       100       110       120
                 ....*....|....*....|....*....|....*....|....*...
gi 409264659 144 SYDSILALVCKEPTQSKPDLHLFQCDEVKANLISEDIESAISDSKGGK 191
Cdd:cd01210   84 SYNSILLLVVQEPDQPKPEMHLFQCDEVGAELLVEDLQKALSGKRSGR 131
PTB pfam08416
Phosphotyrosine-binding domain; The phosphotyrosine-binding domain (PTB, also ...
64-194 7.75e-68

Phosphotyrosine-binding domain; The phosphotyrosine-binding domain (PTB, also phosphotyrosine-interaction or PI domain) in the protein tensin tends to be found at the C-terminus. Tensin is a multi-domain protein that binds to actin filaments and functions as a focal-adhesion molecule (focal adhesions are regions of plasma membrane through which cells attach to the extracellular matrix). Human tensin has actin-binding sites, an SH2 (pfam00017) domain and a region similar to the tumour suppressor PTEN. The PTB domain interacts with the cytoplasmic tails of beta integrin by binding to an NPXY motif.


Pssm-ID: 429984  Cd Length: 131  Bit Score: 220.68  E-value: 7.75e-68
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 409264659   64 QYRVEHLTTFVLDRKDAMITVEDGIRKLKLLDAKGKVWTQDMILQVDDRAVSLIDLESKNELENFPLNTISHCQAVVHAC 143
Cdd:pfam08416   1 QYRVEHLTTFELDSLTGLQAVEDAIRKLQLLDAQGRVWTQEMLLQVSDQGITLTDNETKEELESYPLDSISHCQAVLNDG 80
                          90       100       110       120       130
                  ....*....|....*....|....*....|....*....|....*....|.
gi 409264659  144 SYDSILALVCKEPTQSKPDLHLFQCDEVKANLISEDIESAISDSKGGKQKR 194
Cdd:pfam08416  81 RYNSILALVCQEPGQSKPDVHLFQCDELGAELIAEDIESALSDVRLGKPKK 131
SAM_EPS8-like cd09540
SAM domain of EPS8-like subfamily; SAM (sterile alpha motif) domain of EPS8-like subfamily is ...
719-783 5.58e-37

SAM domain of EPS8-like subfamily; SAM (sterile alpha motif) domain of EPS8-like subfamily is a putative protein-protein interaction domain. This subfamily includes epidermal growth factor receptor kinase substrate 8 proteins (EPS8) and epidermal growth factor receptor kinase substrate 8-like (EPSL8) 1, 2, 3 proteins with the SAM domain located in the C-terminal effector region. This region is responsible for intracellular protein localization and is involved in small GTPases (such as Rac and Rab5) activation/inhibition. Proteins belonging to this group participate in coordination and integration of multiple signaling pathways; in particular, they play a role in the control of actin dynamics and in receptor endocytosis. They can form complexes with other proteins; for example, in the actin signaling network they interact with SOS1 and E3b1 (Abl1) proteins as well as with CRIB (via SH3 domains) during the actin filament formation, and in the receptor endocytosis their partner is RN-tre protein.


Pssm-ID: 188939  Cd Length: 66  Bit Score: 132.84  E-value: 5.58e-37
                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 409264659 719 NITYDSSPEEVKTWLQSKGFNPVTVNSLGVLNGAQLFSLNKDELRSVCP-EGARVFNQITVQKAAL 783
Cdd:cd09540    1 PLTYDSSPEEVKAWLQAKGFSKITVRSLGVLTGAQLFSLNKEELKTVCPeEGARVYSQLTVQKSAL 66
SH3_Eps8 cd11764
Src Homology 3 domain of Epidermal growth factor receptor kinase substrate 8 and similar ...
534-587 8.05e-29

Src Homology 3 domain of Epidermal growth factor receptor kinase substrate 8 and similar proteins; This group is composed of Eps8 and Eps8-like proteins including Eps8-like 1-3, among others. These proteins contain N-terminal Phosphotyrosine-binding (PTB), central SH3, and C-terminal effector domains. Eps8 binds either Abi1 (also called E3b1) or Rab5 GTPase activating protein RN-tre through its SH3 domain. With Abi1 and Sos1, it becomes part of a trimeric complex that is required to activate Rac. Together with RN-tre, it inhibits the internalization of EGFR. The SH3 domains of Eps8 and similar proteins recognize peptides containing a PxxDY motif, instead of the classical PxxP motif. SH3 domains are protein interaction domains that usually bind to proline-rich ligands with moderate affinity and selectivity. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 212698 [Multi-domain]  Cd Length: 54  Bit Score: 108.89  E-value: 8.05e-29
                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|....
gi 409264659 534 YAKSKYDFVARNSSELSVMKDDVLEILDDRRQWWKVRNASGDSGFVPNNILDIM 587
Cdd:cd11764    1 YVRVLYDFTARNSKELSVLKGEYLEVLDDSRQWWKVRNSRGQVGYVPHNILEPY 54
PTB smart00462
Phosphotyrosine-binding domain, phosphotyrosine-interaction (PI) domain; PTB/PI domain ...
64-197 7.52e-26

Phosphotyrosine-binding domain, phosphotyrosine-interaction (PI) domain; PTB/PI domain structure similar to those of pleckstrin homology (PH) and IRS-1-like PTB domains.


Pssm-ID: 214675  Cd Length: 134  Bit Score: 103.55  E-value: 7.52e-26
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 409264659    64 QYRVEHLTTFVLDRKDAMITVEDGIRKLKLLDAKGKVWTQDMILQVDDRAVSLIDLESKNELENFPLNTISHCQAVVHac 143
Cdd:smart00462   5 SFRVKYLGSVEVPEARGLQVVQEAIRKLRAAQGSEKKEPQKVILSISSRGVKLIDEDTKAVLHEHPLRRISFCAVGPD-- 82
                           90       100       110       120       130
                   ....*....|....*....|....*....|....*....|....*....|....
gi 409264659   144 sYDSILALVCKEPTQSKPDLHLFQCDEVkANLISEDIESAISDSKGGKQKRRPE 197
Cdd:smart00462  83 -DLDVFGYIARDPGSSRFACHVFRCEKA-AEDIALAIGQAFQLAYELKLKARSE 134
SAM_3 pfam18016
SAM domain (Sterile alpha motif);
718-777 9.44e-21

SAM domain (Sterile alpha motif);


Pssm-ID: 436214  Cd Length: 65  Bit Score: 86.55  E-value: 9.44e-21
                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|..
gi 409264659  718 INITYDSSPEEVKTWLQSKGFNPVTVNSLGVLNGAQLFSLNKDELRSVCP--EGARVFNQIT 777
Cdd:pfam18016   4 INITPKSTPEEVQAWLTAKGFSKKTVKSLGTLSGAQLFSLSKEELKQICGpaEGIRLYSQLL 65
PTB cd00934
Phosphotyrosine-binding (PTB) PH-like fold; PTB domains have a common PH-like fold and are ...
65-183 1.19e-14

Phosphotyrosine-binding (PTB) PH-like fold; PTB domains have a common PH-like fold and are found in various eukaryotic signaling molecules. This domain was initially shown to bind peptides with a NPXY motif with differing requirements for phosphorylation of the tyrosine, although more recent studies have found that some types of PTB domains can bind to peptides lack tyrosine residues altogether. In contrast to SH2 domains, which recognize phosphotyrosine and adjacent carboxy-terminal residues, PTB-domain binding specificity is conferred by residues amino-terminal to the phosphotyrosine. PTB domains are classified into three groups: phosphotyrosine-dependent Shc-like, phosphotyrosine-dependent IRS-like, and phosphotyrosine-independent Dab-like PTB domains.


Pssm-ID: 269911  Cd Length: 120  Bit Score: 71.00  E-value: 1.19e-14
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 409264659  65 YRVEHLTTFVLDRKDAMITVEDGIRKLKLLDAKGKVWTQDMILQVDDRAVSLIDLESKNELENFPLNTISHCQAVVhacS 144
Cdd:cd00934    3 FQVKYLGSVEVGSSRGVDVVEEALKALAAALKSSKRKPGPVLLEVSSKGVKLLDLDTKELLLRHPLHRISYCGRDP---D 79
                         90       100       110       120
                 ....*....|....*....|....*....|....*....|
gi 409264659 145 YDSILALVCKEPTQSKPDLHLFQC-DEVKANLISEDIESA 183
Cdd:cd00934   80 NPNVFAFIAGEEGGSGFRCHVFQCeDEEEAEEILQAIGQA 119
SH3_Nck_1 cd11765
First Src Homology 3 domain of Nck adaptor proteins; Nck adaptor proteins regulate actin ...
534-582 1.01e-13

First Src Homology 3 domain of Nck adaptor proteins; Nck adaptor proteins regulate actin cytoskeleton dynamics by linking proline-rich effector molecules to protein tyrosine kinases and phosphorylated signaling intermediates. They contain three SH3 domains and a C-terminal SH2 domain. They function downstream of the PDGFbeta receptor and are involved in Rho GTPase signaling and actin dynamics. Vertebrates contain two Nck adaptor proteins: Nck1 (also called Nckalpha) and Nck2 (also called Nckbeta or Growth factor receptor-bound protein 4, Grb4), which show partly overlapping functions but also bind distinct targets. Their SH3 domains are involved in recruiting downstream effector molecules, such as the N-WASP/Arp2/3 complex, which when activated induces actin polymerization that results in the production of pedestals, or protrusions of the plasma membrane. The first SH3 domain of Nck proteins preferentially binds the PxxDY sequence, which is present in the CD3e cytoplasmic tail. This binding inhibits phosphorylation by Src kinases, resulting in the downregulation of TCR surface expression. SH3 domains are protein interaction domains that usually bind to proline-rich ligands with moderate affinity and selectivity, preferentially a PxxP motif. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 212699 [Multi-domain]  Cd Length: 51  Bit Score: 65.90  E-value: 1.01e-13
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gi 409264659 534 YAKSKYDFVARNSSELSVMKDDVLEILDDRRQWWKVRNASGDSGFVPNN 582
Cdd:cd11765    1 YVVAKYDYTAQGDQELSIKKNEKLTLLDDSKHWWKVQNSSNQTGYVPSN 49
SH3 smart00326
Src homology 3 domains; Src homology 3 (SH3) domains bind to target proteins through sequences ...
531-584 5.87e-13

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: 64.10  E-value: 5.87e-13
                           10        20        30        40        50
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gi 409264659   531 PKKYAKSKYDFVARNSSELSVMKDDVLEILDDRRQ-WWKVRNASGDSGFVPNNIL 584
Cdd:smart00326   1 EGPQVRALYDYTAQDPDELSFKKGDIITVLEKSDDgWWKGRLGRGKEGLFPSNYV 55
SH3 cd00174
Src Homology 3 domain superfamily; Src Homology 3 (SH3) domains are protein interaction ...
534-582 1.12e-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: 57.47  E-value: 1.12e-10
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gi 409264659 534 YAKSKYDFVARNSSELSVMKDDVLEILDDRRQ-WWKVRNASGDSGFVPNN 582
Cdd:cd00174    1 YARALYDYEAQDDDELSFKKGDIITVLEKDDDgWWEGELNGGREGLFPAN 50
SH3_1 pfam00018
SH3 domain; SH3 (Src homology 3) domains are often indicative of a protein involved in signal ...
536-580 2.16e-10

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: 56.44  E-value: 2.16e-10
                          10        20        30        40
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gi 409264659  536 KSKYDFVARNSSELSVMKDDVLEILDD-RRQWWKVRNASGDSGFVP 580
Cdd:pfam00018   1 VALYDYTAQEPDELSFKKGDIIIVLEKsEDGWWKGRNKGGKEGLIP 46
SH3_Tec_like cd11768
Src Homology 3 domain of Tec-like Protein Tyrosine Kinases; The Tec (Tyrosine kinase expressed ...
537-582 3.01e-10

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


Pssm-ID: 212702 [Multi-domain]  Cd Length: 54  Bit Score: 56.13  E-value: 3.01e-10
                         10        20        30        40
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gi 409264659 537 SKYDFVARNSSELSVMKDDVLEILDDRRQ-WWKVRNASGDSGFVPNN 582
Cdd:cd11768    4 ALYDFQPIEPGDLPLEKGEEYVVLDDSNEhWWRARDKNGNEGYIPSN 50
SH3_Nck1_1 cd11900
First Src Homology 3 domain of Nck1 adaptor protein; Nck1 (also called Nckalpha) plays a ...
537-585 9.51e-10

First Src Homology 3 domain of Nck1 adaptor protein; Nck1 (also called Nckalpha) plays a crucial role in connecting signaling pathways of tyrosine kinase receptors and important effectors in actin dynamics and cytoskeletal remodeling. It binds and activates RasGAP, resulting in the downregulation of Ras. It is also involved in the signaling of endothilin-mediated inhibition of cell migration. Nck adaptor proteins regulate actin cytoskeleton dynamics by linking proline-rich effector molecules to protein tyrosine kinases and phosphorylated signaling intermediates. They contain three SH3 domains and a C-terminal SH2 domain. They function downstream of the PDGFbeta receptor and are involved in Rho GTPase signaling and actin dynamics. Vertebrates contain two Nck adaptor proteins: Nck1 (also called Nckalpha) and Nck2, which show partly overlapping functions but also bind distinct targets. The first SH3 domain of Nck1 binds the PxxDY sequence in the CD3e cytoplasmic tail; this binding inhibits phosphorylation by Src kinases, resulting in the downregulation of TCR surface expression. SH3 domains are protein interaction domains that usually bind to proline-rich ligands with moderate affinity and selectivity, preferentially a PxxP motif. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 212833 [Multi-domain]  Cd Length: 59  Bit Score: 55.11  E-value: 9.51e-10
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gi 409264659 537 SKYDFVARNSSELSVMKDDVLEILDDRRQWWKVRNASGDSGFVPNNILD 585
Cdd:cd11900    7 AKFDYVAQQDQELDIKKNERLWLLDDSKSWWRVRNAMNKTGFVPSNYVE 55
SH3_Sla1p_3 cd11775
Third Src Homology 3 domain of the fungal endocytic adaptor protein Sla1p; Sla1p facilitates ...
533-586 2.73e-09

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


Pssm-ID: 212709 [Multi-domain]  Cd Length: 57  Bit Score: 53.48  E-value: 2.73e-09
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gi 409264659 533 KYAKSKYDFVARNSSELSVMKDDVLEILDDR--RQWWKVRNAS-GDSGFVPNNILDI 586
Cdd:cd11775    1 KRGKVLYDFDAQSDDELTVKEGDVVYILDDKksKDWWMVENVStGKEGVVPASYIEI 57
SH3_Nck2_1 cd11899
First Src Homology 3 domain of Nck2 adaptor protein; Nck2 (also called Nckbeta or Growth ...
537-585 3.62e-09

First Src Homology 3 domain of Nck2 adaptor protein; Nck2 (also called Nckbeta or Growth factor receptor-bound protein 4, Grb4) plays a crucial role in connecting signaling pathways of tyrosine kinase receptors and important effectors in actin dynamics and cytoskeletal remodeling. It binds neuronal signaling proteins such as ephrinB and Disabled-1 (Dab-1) exclusively. Nck adaptor proteins regulate actin cytoskeleton dynamics by linking proline-rich effector molecules to protein tyrosine kinases and phosphorylated signaling intermediates. They contain three SH3 domains and a C-terminal SH2 domain. They function downstream of the PDGFbeta receptor and are involved in Rho GTPase signaling and actin dynamics. Vertebrates contain two Nck adaptor proteins: Nck1 (also called Nckalpha) and Nck2, which show partly overlapping functions but also bind distinct targets. The first SH3 domain of Nck2 binds the PxxDY sequence in the CD3e cytoplasmic tail; this binding inhibits phosphorylation by Src kinases, resulting in the downregulation of TCR surface expression. SH3 domains are protein interaction domains that usually bind to proline-rich ligands with moderate affinity and selectivity, preferentially a PxxP motif. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 212832 [Multi-domain]  Cd Length: 58  Bit Score: 53.21  E-value: 3.62e-09
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gi 409264659 537 SKYDFVARNSSELSVMKDDVLEILDDRRQWWKVRNASGDSGFVPNNILD 585
Cdd:cd11899    8 AKWDYTAQQDQELDIKKNERLWLLDDSKTWWRVRNAANRTGYVPSNYVE 56
SH3_Nck_3 cd11767
Third Src Homology 3 domain of Nck adaptor proteins; This group contains the third SH3 domain ...
539-582 3.63e-09

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: 53.08  E-value: 3.63e-09
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gi 409264659 539 YDFVARNSSELSVMKDDVLEILD---DRRQWWKVRNASGDSGFVPNN 582
Cdd:cd11767    6 YPFTGENDEELSFEKGERLEIIEkpeDDPDWWKARNALGTTGLVPRN 52
SH3_Src_like cd11845
Src homology 3 domain of Src kinase-like Protein Tyrosine Kinases; Src subfamily members ...
539-582 4.03e-09

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


Pssm-ID: 212779 [Multi-domain]  Cd Length: 52  Bit Score: 52.97  E-value: 4.03e-09
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gi 409264659 539 YDFVARNSSELSVMKDDVLEILDDRR-QWWKVRN-ASGDSGFVPNN 582
Cdd:cd11845    6 YDYEARTDDDLSFKKGDRLQILDDSDgDWWLARHlSTGKEGYIPSN 51
SH3_FCHSD_1 cd11761
First Src Homology 3 domain of FCH and double SH3 domains proteins; This group is composed of ...
539-586 1.29e-08

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


Pssm-ID: 212695 [Multi-domain]  Cd Length: 57  Bit Score: 51.60  E-value: 1.29e-08
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gi 409264659 539 YDFVARNSSELSVMKDDVLEIL--DDRRQWWKVRNASGDSGFVPNNILDI 586
Cdd:cd11761    8 YSYEAQRPDELTITEGEELEVIedGDGDGWVKARNKSGEVGYVPENYLQF 57
SH3_SNX9_like cd11763
Src Homology 3 domain of Sorting Nexin 9 and similar proteins; Sorting nexins (SNXs) are Phox ...
534-580 2.34e-07

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


Pssm-ID: 212697 [Multi-domain]  Cd Length: 55  Bit Score: 48.09  E-value: 2.34e-07
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gi 409264659 534 YAKSKYDFVARNSSELSVMKDDVLEIL--DDRRQWWKVRNASGDSGFVP 580
Cdd:cd11763    1 KVRALYDFDSQPSGELSLRAGEVLTITrqDVGDGWLEGRNSRGEVGLFP 49
SH3_CSK cd11769
Src Homology 3 domain of C-terminal Src kinase; CSK is a cytoplasmic (or nonreceptor) tyr ...
538-582 2.48e-07

Src Homology 3 domain of C-terminal Src kinase; CSK is a cytoplasmic (or nonreceptor) tyr kinase containing the Src homology domains, SH3 and SH2, N-terminal to the catalytic tyr kinase domain. They negatively regulate the activity of Src kinases that are anchored to the plasma membrane. To inhibit Src kinases, CSK is translocated to the membrane via binding to specific transmembrane proteins, G-proteins, or adaptor proteins near the membrane. CSK catalyzes the tyr phosphorylation of the regulatory C-terminal tail of Src kinases, resulting in their inactivation. It is expressed in a wide variety of tissues and plays a role, as a regulator of Src, in cell proliferation, survival, and differentiation, and consequently, in cancer development and progression. In addition, CSK also shows Src-independent functions. It is a critical component in G-protein signaling, and plays a role in cytoskeletal reorganization and cell migration. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 212703 [Multi-domain]  Cd Length: 57  Bit Score: 48.07  E-value: 2.48e-07
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gi 409264659 538 KYDFVARNSSELSVMKDDVLEILDDRR--QWWKVRNASGDSGFVPNN 582
Cdd:cd11769    7 KYNFNGASEEDLPFKKGDILTIVAVTKdpNWYKAKNKDGREGMIPAN 53
SH3_Pex13p_fungal cd11771
Src Homology 3 domain of fungal peroxisomal membrane protein Pex13p; Pex13p, located in the ...
534-586 2.49e-07

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: 48.04  E-value: 2.49e-07
                         10        20        30        40        50        60
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gi 409264659 534 YAKSKYDFVARNSS-ELSVMKDDVLEIL---DDRRQ---WWKVRNASGDSGFVPNNILDI 586
Cdd:cd11771    1 FCRALYDFTPENPEmELSLKKGDIVAVLsktDPLGRdseWWKGRTRDGRIGWFPSNYVEV 60
SH3_Sho1p cd11855
Src homology 3 domain of High osmolarity signaling protein Sho1p; Sho1p (or Sho1), also called ...
539-584 4.57e-07

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: 47.41  E-value: 4.57e-07
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gi 409264659 539 YDFVARNSSELSVMKDDVLEILDDRRQWWKVRNASGDSGFVPNNIL 584
Cdd:cd11855    8 YDASPDDPNELSFEKGEILEVSDTSGKWWQARKSNGETGICPSNYL 53
SH3_Kalirin_1 cd11852
First Src homology 3 domain of the RhoGEF kinase, Kalirin; Kalirin, also called Duo, Duet, or ...
540-586 1.26e-06

First Src homology 3 domain of the RhoGEF kinase, Kalirin; Kalirin, also called Duo, Duet, or TRAD, is a large neuronal dual Rho guanine nucleotide exchange factor (RhoGEF) that activates Rac1, RhoA, and RhoG using two RhoGEF domains. Kalirin exists in many isoforms generated by alternative splicing and the use of multiple promoters; the major isoforms are kalirin-7, -9, and -12, which differ at their C-terminal ends. Kalirin-12, the longest isoform, contains an N-terminal Sec14p domain, spectrin-like repeats, two RhoGEF domains, two SH3 domains, as well as Ig, FNIII, and kinase domains at the C-terminal end. Kalirin-7 contains only a single RhoGEF domain and does not contain an SH3 domain. Kalirin, through its many isoforms, interacts with many different proteins and is able to localize to different locations within the cell. It influences neurite initiation, axon growth, dendritic morphogenesis, vesicle trafficking, neuronal maintenance, and neurodegeneration. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 212786  Cd Length: 62  Bit Score: 46.23  E-value: 1.26e-06
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gi 409264659 540 DFVARNSSELSVMKDDVLEILD---DRRQWWKVR-----NASGDSGFVPNNILDI 586
Cdd:cd11852    8 DFEATSSQELTVSKGQTVEVLErpsSRPDWCLVRtleqdNSPPQEGLVPSSILCI 62
SH3_PSTPIP1 cd11824
Src homology 3 domain of Proline-Serine-Threonine Phosphatase-Interacting Protein 1; PSTPIP1, ...
539-584 1.39e-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: 45.83  E-value: 1.39e-06
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gi 409264659 539 YDFVARNSSELSVMKDDVLEILD-DRRQWWKV-RNasGDSGFVPNNIL 584
Cdd:cd11824    6 YDYTAQEDDELSISKGDVVAVIEkGEDGWWTVeRN--GQKGLVPGTYL 51
SH3_GRAP2_N cd11947
N-terminal Src homology 3 domain of GRB2-related adaptor protein 2; GRAP2 is also called GADS ...
535-586 1.54e-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: 45.56  E-value: 1.54e-06
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gi 409264659 535 AKSKYDFVARNSSELSVMKDDVLEILDDRRQWWKVRnASGDSGFVPNNILDI 586
Cdd:cd11947    2 ARGKFDFTASGEDELSFKKGDVLKILSSDDIWFKAE-LNGEEGYVPKNFVDI 52
SH3_VAV1_2 cd11976
C-terminal (or second) Src homology 3 domain of VAV1 protein; VAV1 is expressed predominantly ...
535-585 1.74e-06

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: 45.71  E-value: 1.74e-06
                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|...
gi 409264659 535 AKSKYDFVARNSSELSVMKDDVLEILDDRRQ--WWKvRNASGDSGFVPNNILD 585
Cdd:cd11976    2 AKARYDFCARDRSELSLKEGDIIKILNKKGQqgWWR-GEIYGRVGWFPANYVE 53
SH3_Bzz1_1 cd11912
First Src Homology 3 domain of Bzz1 and similar domains; Bzz1 (or Bzz1p) is a WASP ...
535-586 1.82e-06

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


Pssm-ID: 212845 [Multi-domain]  Cd Length: 55  Bit Score: 45.68  E-value: 1.82e-06
                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|....
gi 409264659 535 AKSKYDFVARNSSELSVMKDDVLEIL--DDRRQWWKVRNASGDSGFVPNNILDI 586
Cdd:cd11912    2 AKVLYDYTASGDDEVSISEGEEVTVLepDDGSGWTKVRNGSGEEGLVPTSYIEI 55
SH3_CRK_N cd11758
N-terminal Src Homology 3 domain of Ct10 Regulator of Kinase adaptor proteins; CRK adaptor ...
534-580 2.20e-06

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: 45.43  E-value: 2.20e-06
                         10        20        30        40
                 ....*....|....*....|....*....|....*....|....*...
gi 409264659 534 YAKSKYDFVARNSSELSVMKDDVLEILD-DRRQWWKVRNASGDSGFVP 580
Cdd:cd11758    2 YVRALFDFPGNDDEDLPFKKGEILTVIRkPEEQWWNARNSEGKTGMIP 49
PID pfam00640
Phosphotyrosine interaction domain (PTB/PID);
67-185 3.93e-06

Phosphotyrosine interaction domain (PTB/PID);


Pssm-ID: 395515  Cd Length: 133  Bit Score: 46.97  E-value: 3.93e-06
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 409264659   67 VEHLTTFVLDRKDAMITVEDGIRKLKLLDAKGKVWT-------QDMILQVDDRAVSLIDLESKNELENFPLNTISHCqAV 139
Cdd:pfam00640   9 VEVPEERAPDKNTRMQQAREAIRRVKAAKINKIRGLsgetgpgTKVDLFISTDGLKLLNPDTQELIHDHPLVSISFC-AD 87
                          90       100       110       120
                  ....*....|....*....|....*....|....*....|....*.
gi 409264659  140 VHAcSYDSILALVCKEPTQSKPDLHLFQCDEvKANLISEDIESAIS 185
Cdd:pfam00640  88 GDP-DLMRYFAYIARDKATNKFACHVFESED-GAQDIAQSIGQAFA 131
SH3_Myosin-I_fungi cd11858
Src homology 3 domain of Type I fungal Myosins; Type I myosins (myosin-I) are actin-dependent ...
535-584 4.47e-06

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: 44.68  E-value: 4.47e-06
                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|..
gi 409264659 535 AKSKYDFVARNSSELSVMKDDVLEIL-DDRRQWWKVRNASGD-SGFVPNNIL 584
Cdd:cd11858    2 YKALYDFAGSVANELSLKKDDIVYIVqKEDNGWWLAKKLDESkEGWVPAAYL 53
PTB_LDLRAP-mammal-like cd13159
Low Density Lipoprotein Receptor Adaptor Protein 1 (LDLRAP1) in mammals and similar proteins ...
64-168 4.89e-06

Low Density Lipoprotein Receptor Adaptor Protein 1 (LDLRAP1) in mammals and similar proteins Phosphotyrosine-binding (PTB) PH-like fold; The null mutations in the LDL receptor adaptor protein 1 (LDLRAP1) gene, which serves as an adaptor for LDLR endocytosis in the liver, causes autosomal recessive hypercholesterolemia (ARH). LDLRAP1 contains a single PTB domain. PTB domains have a common PH-like fold and are found in various eukaryotic signaling molecules. This domain was initially shown to binds peptides with a NPXY motif with differing requirements for phosphorylation of the tyrosine, although more recent studies have found that some types of PTB domains can bind to peptides lack tyrosine residues altogether. In contrast to SH2 domains, which recognize phosphotyrosine and adjacent carboxy-terminal residues, PTB-domain binding specificity is conferred by residues amino-terminal to the phosphotyrosine. PTB domains are classified into three groups: phosphotyrosine-dependent Shc-like, phosphotyrosine-dependent IRS-like, and phosphotyrosine-independent Dab-like PTB domains. This cd contains mammals, insects, and sponges.


Pssm-ID: 269981  Cd Length: 123  Bit Score: 46.56  E-value: 4.89e-06
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 409264659  64 QYRVEHL-TTFVLDRKDAMITVEDGIRKLKLLDAKGKVWtQDMILQVDDRAVSLIDLESKNELENFPLNTISHCQAvvhA 142
Cdd:cd13159    4 TFYLKYLgSTLVEKPKGEGATAEAVKTIIAMAKASGKKL-QKVTLTVSPKGIKVTDSATNETILEVSIYRISYCTA---D 79
                         90       100
                 ....*....|....*....|....*.
gi 409264659 143 CSYDSILALVCKEPTQSKPDLHLFQC 168
Cdd:cd13159   80 ANHDKVFAFIATNQDNEKLECHAFLC 105
SH3_Nephrocystin cd11770
Src Homology 3 domain of Nephrocystin (or Nephrocystin-1); Nephrocystin contains an SH3 domain ...
539-584 6.53e-06

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: 43.84  E-value: 6.53e-06
                         10        20        30        40
                 ....*....|....*....|....*....|....*....|....*..
gi 409264659 539 YDFVARNSSELSVMKDDVLEILDDRRQ-WWKVRNASGDSGFVPNNIL 584
Cdd:cd11770    6 SDFQAEQEGDLSFKKGEVLRIISKRADgWWLAENSKGNRGLVPKTYL 52
SH3_Nck1_3 cd11904
Third Src Homology 3 domain of Nck1 adaptor protein; Nck1 (also called Nckalpha) plays a ...
539-586 1.19e-05

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: 43.48  E-value: 1.19e-05
                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|.
gi 409264659 539 YDFVARNSSELSVMKDDVLEILD---DRRQWWKVRNASGDSGFVPNNILDI 586
Cdd:cd11904    7 YPFSSSNDEELNFEKGEVMDVIEkpeNDPEWWKCRKANGQVGLVPKNYVTV 57
SH3_VAV_2 cd11830
C-terminal (or second) Src homology 3 domain of VAV proteins; VAV proteins function both as ...
535-585 1.90e-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: 42.62  E-value: 1.90e-05
                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|...
gi 409264659 535 AKSKYDFVARNSSELSVMKDDVLEILDDRRQ--WWKvRNASGDSGFVPNNILD 585
Cdd:cd11830    2 AKARYDFCARDMRELSLKEGDVVKIYNKKGQqgWWR-GEINGRIGWFPSTYVE 53
SH3_GRAP_C cd11951
C-terminal Src homology 3 domain of GRB2-related adaptor protein; GRAP is a GRB-2 like adaptor ...
534-582 2.55e-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: 42.48  E-value: 2.55e-05
                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|
gi 409264659 534 YAKSKYDFVARNSSELSVMKDDVLEILD-DRRQWWKVRnASGDSGFVPNN 582
Cdd:cd11951    1 FVQAQYDFSAEDPSQLSFRRGDIIEVLDcPDPNWWRGR-ISGRVGFFPRN 49
SH3_Blk cd12009
Src homology 3 domain of Blk Protein Tyrosine Kinase; Blk is a member of the Src subfamily of ...
539-582 2.83e-05

Src homology 3 domain of Blk Protein Tyrosine Kinase; Blk is a member of the Src subfamily of proteins, which are cytoplasmic (or non-receptor) PTKs. It is expressed specifically in B-cells and is involved in pre-BCR (B-cell receptor) signaling. Src kinases contain an N-terminal SH4 domain with a myristoylation site, followed by SH3 and SH2 domains, a tyr kinase domain, and a regulatory C-terminal region containing a conserved tyr. They are activated by autophosphorylation at the tyr kinase domain, but are negatively regulated by phosphorylation at the C-terminal tyr by Csk (C-terminal Src Kinase). The SH3 domain of Src kinases contributes to substrate recruitment by binding adaptor proteins/substrates, and regulation of kinase activity through an intramolecular interaction. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 212942 [Multi-domain]  Cd Length: 54  Bit Score: 42.11  E-value: 2.83e-05
                         10        20        30        40
                 ....*....|....*....|....*....|....*....|....*
gi 409264659 539 YDFVARNSSELSVMKDDVLEILDDRRQWWKVRN-ASGDSGFVPNN 582
Cdd:cd12009    6 YDFVPSNERDLQLKKGEKLQVLKSDGEWWLAKSlTTGKEGYIPSN 50
SH3_Nck2_3 cd11903
Third Src Homology 3 domain of Nck2 adaptor protein; Nck2 (also called Nckbeta or Growth ...
536-587 3.31e-05

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


Pssm-ID: 212836 [Multi-domain]  Cd Length: 59  Bit Score: 42.35  E-value: 3.31e-05
                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|....*
gi 409264659 536 KSKYDFVARNSSELSVMKDDVLEIL---DDRRQWWKVRNASGDSGFVPNNILDIM 587
Cdd:cd11903    4 QTLYPFSSVTEEELNFEKGETMEVIekpENDPEWWKCKNSRGQVGLVPKNYVVVL 58
SH3_GRB2_N cd11946
N-terminal Src homology 3 domain of Growth factor receptor-bound protein 2; GRB2 is a critical ...
535-586 3.74e-05

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: 41.93  E-value: 3.74e-05
                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|....
gi 409264659 535 AKSKYDFVARNSSELSVMKDDVLEILDDR--RQWWKVRnASGDSGFVPNNILDI 586
Cdd:cd11946    3 AIAKYDFKATADDELSFKRGDILKVLNEEcdQNWYKAE-LNGKDGFIPKNYIEM 55
SH3_2 pfam07653
Variant SH3 domain; SH3 (Src homology 3) domains are often indicative of a protein involved in ...
534-584 3.80e-05

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: 41.81  E-value: 3.80e-05
                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|..
gi 409264659  534 YAKSKYDFVARNSSELSVMKDDVLEILDDRR-QWWKVRNaSGDSGFVPNNIL 584
Cdd:pfam07653   1 YGRVIFDYVGTDKNGLTLKKGDVVKVLGKDNdGWWEGET-GGRVGLVPSTAV 51
SH3_GRB2_like_N cd11804
N-terminal Src homology 3 domain of Growth factor receptor-bound protein 2 (GRB2) and related ...
535-582 4.05e-05

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


Pssm-ID: 212738 [Multi-domain]  Cd Length: 52  Bit Score: 41.57  E-value: 4.05e-05
                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|
gi 409264659 535 AKSKYDFVARNSSELSVMKDDVLEIL--DDRRQWWKVRnASGDSGFVPNN 582
Cdd:cd11804    2 AVAKHDFKATAEDELSFKKGSILKVLnmEDDPNWYKAE-LDGKEGLIPKN 50
SH3_Brk cd11847
Src homology 3 domain of Brk (Breast tumor kinase) Protein Tyrosine Kinase (PTK), also called ...
539-584 5.73e-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: 41.39  E-value: 5.73e-05
                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|.
gi 409264659 539 YDFVARNSSELSVMKDDVLEILDDRRQWWKVRNASGD-----SGFVPNNIL 584
Cdd:cd11847    6 WDFKARGDEELSFQAGDQFRIAERSGDWWTALKLDRAggvvaQGFVPNNYL 56
SH3_Alpha_Spectrin cd11808
Src homology 3 domain of Alpha Spectrin; Spectrin is a major structural component of the red ...
534-584 9.48e-05

Src homology 3 domain of Alpha Spectrin; Spectrin is a major structural component of the red blood cell membrane skeleton and is important in erythropoiesis and membrane biogenesis. It is a flexible, rope-like molecule composed of two subunits, alpha and beta, which consist of many spectrin-type repeats. Alpha and beta spectrin associate to form heterodimers and tetramers; spectrin tetramer formation is critical for red cell shape and deformability. Defects in alpha spectrin have been associated with inherited hemolytic anemias including hereditary spherocytosis (HSp), hereditary elliptocytosis (HE), and hereditary pyropoikilocytosis (HPP). Alpha spectrin contains a middle SH3 domain and a C-terminal EF-hand binding motif in addition to multiple spectrin repeats. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 212742 [Multi-domain]  Cd Length: 53  Bit Score: 40.55  E-value: 9.48e-05
                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|..
gi 409264659 534 YAKSKYDFVARNSSELSVMKDDVLEILD-DRRQWWKVRNaSGDSGFVPNNIL 584
Cdd:cd11808    1 CVVALYDYQEKSPREVSMKKGDILTLLNsSNKDWWKVEV-NDRQGFVPAAYV 51
SH3_DNMBP_C2_like cd11800
Second C-terminal Src homology 3 domain of Dynamin Binding Protein, also called Tuba, and ...
539-585 1.10e-04

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


Pssm-ID: 212734 [Multi-domain]  Cd Length: 57  Bit Score: 40.82  E-value: 1.10e-04
                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|....
gi 409264659 539 YDFVARNSSELSVMKDDVLEILddRRQ-------WWKVRNaSGDSGFVPNNILD 585
Cdd:cd11800    6 YTFEARSPGELSVTEGQVVTVL--EKHdlkgnpeWWLVED-RGKQGYVPSNYLA 56
SH3_9 pfam14604
Variant SH3 domain;
538-585 1.40e-04

Variant SH3 domain;


Pssm-ID: 434066 [Multi-domain]  Cd Length: 49  Bit Score: 39.91  E-value: 1.40e-04
                          10        20        30        40
                  ....*....|....*....|....*....|....*....|....*....
gi 409264659  538 KYDFVARNSSELSVMKDDVLEILDDRRQ-WWKVRNaSGDSGFVPNNILD 585
Cdd:pfam14604   2 LYPYEPKDDDELSLQRGDVITVIEESEDgWWEGIN-TGRTGLVPANYVE 49
SH3_ITK cd11908
Src Homology 3 domain of Interleukin-2-inducible T-cell Kinase; ITK (also known as Tsk or Emt) ...
539-584 1.61e-04

Src Homology 3 domain of Interleukin-2-inducible T-cell Kinase; ITK (also known as Tsk or Emt) is a cytoplasmic (or nonreceptor) tyr kinase containing Src homology protein interaction domains (SH3, SH2) N-terminal to the catalytic tyr kinase domain. It also contains an N-terminal pleckstrin homology (PH) domain, which binds the products of PI3K and allows membrane recruitment and activation, and the Tec homology (TH) domain, which contains proline-rich and zinc-binding regions. ITK is expressed in T-cells and mast cells, and is important in their development and differentiation. Of the three Tec kinases expressed in T-cells, ITK plays the predominant role in T-cell receptor (TCR) signaling. It is activated by phosphorylation upon TCR crosslinking and is involved in the pathway resulting in phospholipase C-gamma1 activation and actin polymerization. It also plays a role in the downstream signaling of the T-cell costimulatory receptor CD28, the T-cell surface receptor CD2, and the chemokine receptor CXCR4. In addition, ITK is crucial for the development of T-helper(Th)2 effector responses. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 212841 [Multi-domain]  Cd Length: 56  Bit Score: 40.00  E-value: 1.61e-04
                         10        20        30        40
                 ....*....|....*....|....*....|....*....|....*..
gi 409264659 539 YDFVARNSSELSVMKDDVLEILDDRR-QWWKVRNASGDSGFVPNNIL 584
Cdd:cd11908    7 YDYQTNDPQELALRYNEEYHLLDSSEiHWWRVQDKNGHEGYVPSSYL 53
SH3_Fyn_Yrk cd12006
Src homology 3 domain of Fyn and Yrk Protein Tyrosine Kinases; Fyn and Yrk (Yes-related kinase) ...
539-584 1.88e-04

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


Pssm-ID: 212939 [Multi-domain]  Cd Length: 56  Bit Score: 40.03  E-value: 1.88e-04
                         10        20        30        40
                 ....*....|....*....|....*....|....*....|....*...
gi 409264659 539 YDFVARNSSELSVMKDDVLEILDDRR-QWWKVRN-ASGDSGFVPNNIL 584
Cdd:cd12006    7 YDYEARTEDDLSFHKGEKFQILNSSEgDWWEARSlTTGETGYIPSNYV 54
SH3_TXK cd11907
Src Homology 3 domain of TXK, also called Resting lymphocyte kinase (Rlk); TXK is a ...
536-582 1.96e-04

Src Homology 3 domain of TXK, also called Resting lymphocyte kinase (Rlk); TXK is a cytoplasmic (or nonreceptor) tyr kinase containing Src homology protein interaction domains (SH3, SH2) N-terminal to the catalytic tyr kinase domain. It also contains an N-terminal cysteine-rich region. Rlk is expressed in T-cells and mast cell lines, and is a key component of T-cell receptor (TCR) signaling. It is important in TCR-stimulated proliferation, IL-2 production and phospholipase C-gamma1 activation. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 212840 [Multi-domain]  Cd Length: 55  Bit Score: 39.94  E-value: 1.96e-04
                         10        20        30        40
                 ....*....|....*....|....*....|....*....|....*...
gi 409264659 536 KSKYDFVARNSSELSVMKDDVLEILDDRR-QWWKVRNASGDSGFVPNN 582
Cdd:cd11907    4 KALYDFLPREPSNLALKRAEEYLILEQYDpHWWKARDRYGNEGLIPSN 51
SH3_CIP4-like cd11911
Src Homology 3 domain of Cdc42-Interacting Protein 4; This subfamily is composed of ...
539-580 2.30e-04

Src Homology 3 domain of Cdc42-Interacting Protein 4; This subfamily is composed of Cdc42-Interacting Protein 4 (CIP4), Formin Binding Protein 17 (FBP17), FormiN Binding Protein 1-Like (FNBP1L), and similar proteins. CIP4 and FNBP1L are Cdc42 effectors that bind Wiskott-Aldrich syndrome protein (WASP) and function in endocytosis. CIP4 and FBP17 bind to the Fas ligand and may be implicated in the inflammatory response. CIP4 may also play a role in phagocytosis. It functions downstream of Cdc42 in PDGF-dependent actin reorganization and cell migration, and also regulates the activity of PDGFRbeta. It uses Src as a substrate in regulating the invasiveness of breast tumor cells. CIP4 may also play a role in the pathogenesis of Huntington's disease. Members of this subfamily typically contain an N-terminal F-BAR (FES-CIP4 Homology and Bin/Amphiphysin/Rvs) domain, a central Cdc42-binding HR1 domain, and a C-terminal SH3 domain. The SH3 domain of CIP4 associates with Gapex-5, a Rab31 GEF. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 212844 [Multi-domain]  Cd Length: 55  Bit Score: 39.55  E-value: 2.30e-04
                         10        20        30        40
                 ....*....|....*....|....*....|....*....|....
gi 409264659 539 YDFVARNSSELSVMKDDVLEIL--DDRRQWWKVRNASGDSGFVP 580
Cdd:cd11911    6 YDFDGTSEGTLSMEEGEILLVLeeDGGDGWTRVRKNNGDEGYVP 49
SH3_Sla1p_1 cd11773
First Src Homology 3 domain of the fungal endocytic adaptor protein Sla1p; Sla1p facilitates ...
535-582 2.47e-04

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


Pssm-ID: 212707 [Multi-domain]  Cd Length: 57  Bit Score: 39.72  E-value: 2.47e-04
                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|....*
gi 409264659 535 AKSKYDFVARNSSELSVMKDDVLEILD-DRRQWWKVR---NASGDS---GFVPNN 582
Cdd:cd11773    2 YKALYDYEPQTEDELTIQEDDILYLLEkSDDDWWKVKlkvNSSDDDepvGLVPAT 56
SH3_Cortactin_like cd11819
Src homology 3 domain of Cortactin and related proteins; This subfamily includes cortactin, ...
535-582 3.11e-04

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


Pssm-ID: 212753 [Multi-domain]  Cd Length: 54  Bit Score: 39.22  E-value: 3.11e-04
                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|.
gi 409264659 535 AKSKYDFVARNSSELSVMKDDV---LEILDDrrQWWKVRNASGDSGFVPNN 582
Cdd:cd11819    2 AKALYDYQAAEDNEISFVEGDIitqIEQIDE--GWWLGVNAKGQKGLFPAN 50
SH3_BTK cd11906
Src Homology 3 domain of Bruton's tyrosine kinase; BTK is a cytoplasmic (or nonreceptor) tyr ...
539-582 3.72e-04

Src Homology 3 domain of Bruton's tyrosine kinase; BTK is a cytoplasmic (or nonreceptor) tyr kinase containing Src homology protein interaction domains (SH3, SH2) N-terminal to the catalytic tyr kinase domain. It also contains an N-terminal pleckstrin homology (PH) domain, which binds the products of PI3K and allows membrane recruitment and activation, and the Tec homology (TH) domain with proline-rich and zinc-binding regions. Btk is expressed in B-cells, and a variety of myeloid cells including mast cells, platelets, neutrophils, and dendrictic cells. It interacts with a variety of partners, from cytosolic proteins to nuclear transcription factors, suggesting a diversity of functions. Stimulation of a diverse array of cell surface receptors, including antigen engagement of the B-cell receptor (BCR), leads to PH-mediated membrane translocation of Btk and subsequent phosphorylation by Src kinase and activation. Btk plays an important role in the life cycle of B-cells including their development, differentiation, proliferation, survival, and apoptosis. Mutations in Btk cause the primary immunodeficiency disease, X-linked agammaglobulinaemia (XLA) in humans. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 212839 [Multi-domain]  Cd Length: 55  Bit Score: 39.04  E-value: 3.72e-04
                         10        20        30        40
                 ....*....|....*....|....*....|....*....|....*
gi 409264659 539 YDFVARNSSELSVMKDDVLEILDD-RRQWWKVRNASGDSGFVPNN 582
Cdd:cd11906    7 YDYTPMNAQDLQLRKGEEYVILEEsNLPWWRARDKNGREGYIPSN 51
SH3_Intersectin_5 cd11840
Fifth Src homology 3 domain (or SH3E) of Intersectin; Intersectins (ITSNs) are adaptor ...
539-582 3.95e-04

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: 38.94  E-value: 3.95e-04
                         10        20        30        40
                 ....*....|....*....|....*....|....*....|....*
gi 409264659 539 YDFVARNSSELSVMKDDVLEILD-DRRQWWKvRNASGDSGFVPNN 582
Cdd:cd11840    6 FPYTAQNEDELSFQKGDIINVLSkDDPDWWR-GELNGQTGLFPSN 49
SH3_p47phox_like cd11856
Src homology 3 domains of the p47phox subunit of NADPH oxidase and similar domains; This ...
539-585 4.29e-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: 38.77  E-value: 4.29e-04
                         10        20        30        40
                 ....*....|....*....|....*....|....*....|....*...
gi 409264659 539 YDFVARNSSELSVMKDDVLEILD-DRRQWWKVRNaSGDSGFVPNNILD 585
Cdd:cd11856    6 ADYEAQGDDEISLQEGEVVEVLEkNDSGWWYVRK-GDKEGWVPASYLE 52
SH3_ASPP cd11807
Src homology 3 domain of Apoptosis Stimulating of p53 proteins (ASPP); The ASPP family of ...
539-584 4.79e-04

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: 38.90  E-value: 4.79e-04
                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|
gi 409264659 539 YDFVARNSSELSVMKDDVLEIL----DDRRQWWKVRNaSGDSGFVPNNIL 584
Cdd:cd11807    7 FDYEAENGDELSFREGDELTVLrkgdDDETEWWWARL-NDKEGYVPRNLL 55
SH3_Intersectin_2 cd11837
Second Src homology 3 domain (or SH3B) of Intersectin; Intersectins (ITSNs) are adaptor ...
539-582 6.00e-04

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: 38.50  E-value: 6.00e-04
                         10        20        30        40
                 ....*....|....*....|....*....|....*....|....
gi 409264659 539 YDFVARNSSELSVMKDDVLEILDDRRQWWKVRNASGDSGFVPNN 582
Cdd:cd11837    6 YPWRAKKENHLSFAKGDIITVLEQQEMWWFGELEGGEEGWFPKS 49
SH3_AHI-1 cd11812
Src Homology 3 domain of Abelson helper integration site-1 (AHI-1); AHI-1, also called ...
537-582 6.31e-04

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: 38.26  E-value: 6.31e-04
                         10        20        30        40
                 ....*....|....*....|....*....|....*....|....*..
gi 409264659 537 SKYDFVARNSSELSVMKDDVLEIL-DDRRQWWKVRNASGDSGFVPNN 582
Cdd:cd11812    4 ALYDYTANRSDELTIHRGDIIRVLyKDNDNWWFGSLVNGQQGYFPAN 50
SH3_PEX13_eumet cd11864
Src Homology 3 domain of eumetazoan Peroxisomal biogenesis factor 13; PEX13 is a peroxin and ...
535-582 6.32e-04

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: 38.38  E-value: 6.32e-04
                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|...
gi 409264659 535 AKSKYDFVARNSSELSVMKDDVLEILDDRRQ-----WWKVRNASGDSGFVPNN 582
Cdd:cd11864    2 ARAEYDFVAESEDELSFRAGDKLRLAPKELQprvrgWLLATVDGQKIGLVPAN 54
SH3_FNBP1L cd12072
Src Homology 3 domain of Formin Binding Protein 1-Like; FormiN Binding Protein 1-Like (FNBP1L), ...
534-586 1.04e-03

Src Homology 3 domain of Formin Binding Protein 1-Like; FormiN Binding Protein 1-Like (FNBP1L), also known as Toca-1 (Transducer of Cdc42-dependent actin assembly), forms a complex with neural Wiskott-Aldrich syndrome protein (N-WASP). The FNBP1L/N-WASP complex induces the formation of filopodia and endocytic vesicles. FNBP1L is required for Cdc42-induced actin assembly and is essential for autophagy of intracellular pathogens. It contains an N-terminal F-BAR domain, a central Cdc42-binding HR1 domain, and a C-terminal SH3 domain. The SH3 domain of the related protein, CIP4, associates with Gapex-5, a Rab31 GEF. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 213005 [Multi-domain]  Cd Length: 57  Bit Score: 38.05  E-value: 1.04e-03
                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|....*
gi 409264659 534 YAKSKYDFVARNSSELSVMKDDVLEILDDRRQ--WWKVRNASGDSGFVPNNILDI 586
Cdd:cd12072    2 HCKALYPFDGSNEGTLAMKEGEVLYIIEEDKGdgWTRARKQNGEEGYVPTSYIEI 56
SH3_SPIN90 cd11849
Src homology 3 domain of SH3 protein interacting with Nck, 90 kDa (SPIN90); SPIN90 is also ...
536-584 1.19e-03

Src homology 3 domain of SH3 protein interacting with Nck, 90 kDa (SPIN90); SPIN90 is also called NCK interacting protein with SH3 domain (NCKIPSD), Dia-interacting protein (DIP), 54 kDa vimentin-interacting protein (VIP54), or WASP-interacting SH3-domain protein (WISH). It is an F-actin binding protein that regulates actin polymerization and endocytosis. It associates with the Arp2/3 complex near actin filaments and determines filament localization at the leading edge of lamellipodia. SPIN90 is expressed in the early stages of neuronal differentiation and plays a role in regulating growth cone dynamics and neurite outgrowth. It also interacts with IRSp53 and regulates cell motility by playing a role in the formation of membrane protrusions. SPIN90 contains an N-terminal SH3 domain, a proline-rich domain, and a C-terminal VCA (verprolin-homology and cofilin-like acidic) domain. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 212783 [Multi-domain]  Cd Length: 53  Bit Score: 37.68  E-value: 1.19e-03
                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|
gi 409264659 536 KSKYDFVARNSSELSVMKDDVLEILDDRRQ-WWKVRNASGDSGFVPNNIL 584
Cdd:cd11849    3 RALYDFKSAEPNTLSFSEGETFLLLERSNAhWWLVTNHSGETGYVPANYV 52
SH3_MyoIe_If_like cd11827
Src homology 3 domain of Myosins Ie, If, and similar proteins; Myosins Ie (MyoIe) and If ...
535-582 1.19e-03

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: 37.78  E-value: 1.19e-03
                         10        20        30        40
                 ....*....|....*....|....*....|....*....|....*....
gi 409264659 535 AKSKYDFVARNSSELSVMKDDVLEIL-DDRRQWWKVRnASGDSGFVPNN 582
Cdd:cd11827    2 CKALYAYDAQDTDELSFNEGDIIEILkEDPSGWWTGR-LRGKEGLFPGN 49
SH3_DNMBP_C2 cd12141
Second C-terminal Src homology 3 domain of Dynamin Binding Protein, also called Tuba, and ...
539-584 1.29e-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. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 213017 [Multi-domain]  Cd Length: 57  Bit Score: 37.48  E-value: 1.29e-03
                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|.
gi 409264659 539 YDFVARNSSELSVMKDDVLEILDDR-----RQWWkVRNASGDSGFVPNNIL 584
Cdd:cd12141    6 YTFKARSPNELSVSANQRVRILEFSdltgnKEWW-LAEANGQKGYVPSNYI 55
SH3_OSTF1 cd11772
Src Homology 3 domain of metazoan osteoclast stimulating factor 1; OSTF1, also named OSF or ...
539-582 1.44e-03

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: 37.28  E-value: 1.44e-03
                         10        20        30        40
                 ....*....|....*....|....*....|....*....|....*
gi 409264659 539 YDFVARNSSELSVMKDDVLEILD-DRRQWWKVRnASGDSGFVPNN 582
Cdd:cd11772    6 YDYEAQHPDELSFEEGDLLYISDkSDPNWWKAT-CGGKTGLIPSN 49
SH3_GRAP_N cd11948
N-terminal Src homology 3 domain of GRB2-related adaptor protein; GRAP is a GRB-2 like adaptor ...
539-586 2.77e-03

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: 36.72  E-value: 2.77e-03
                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|
gi 409264659 539 YDFVARNSSELSVMKDDVLEIL--DDRRQWWKVRnASGDSGFVPNNILDI 586
Cdd:cd11948    6 YSFQATESDELPFQKGDILKILnmEDDQNWYKAE-LQGREGYIPKNYIKV 54
SH3_Bem1p_1 cd11878
First Src Homology 3 domain of Bud emergence protein 1 and similar domains; Members of this ...
536-580 3.11e-03

First Src Homology 3 domain of Bud emergence protein 1 and similar domains; Members of this subfamily bear similarity to Saccharomyces cerevisiae Bem1p, containing two Src Homology 3 (SH3) domains at the N-terminus, a central PX domain, and a C-terminal PB1 domain. Bem1p is a scaffolding protein that is critical for proper Cdc42p activation during bud formation in yeast. During budding and mating, Bem1p migrates to the plasma membrane where it can serve as an adaptor for Cdc42p and some other proteins. Bem1p also functions as an effector of the G1 cyclin Cln3p and the cyclin-dependent kinase Cdc28p in promoting vacuolar fusion. SH3 domains bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs; they play a role in the regulation of enzymes by intramolecular interactions, changing the subcellular localization of signal pathway components and mediate multiprotein complex assemblies.


Pssm-ID: 212811 [Multi-domain]  Cd Length: 54  Bit Score: 36.50  E-value: 3.11e-03
                         10        20        30        40
                 ....*....|....*....|....*....|....*....|....*...
gi 409264659 536 KSKYDFVARNSSELSVMKDDVLEILDDRRQ--WWKVRN-ASGDSGFVP 580
Cdd:cd11878    3 RALYDYRAQTPGELSFSKGDFFHVIGEEDQgeWYEATNpVTGKRGLVP 50
SH3_SNX33 cd11896
Src Homology 3 domain of Sorting Nexin 33; SNX33 interacts with Wiskott-Aldrich syndrome ...
535-586 3.16e-03

Src Homology 3 domain of Sorting Nexin 33; SNX33 interacts with Wiskott-Aldrich syndrome protein (WASP) and plays a role in the maintenance of cell shape and cell cycle progression. It modulates the shedding and endocytosis of cellular prion protein (PrP(c)) and amyloid precursor protein (APP). SNXs are Phox homology (PX) domain containing proteins that are involved in regulating membrane traffic and protein sorting in the endosomal system. SNX33 also contains BAR and SH3 domains. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 212829 [Multi-domain]  Cd Length: 55  Bit Score: 36.48  E-value: 3.16e-03
                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|....
gi 409264659 535 AKSKYDFVARNSSELSVMKDDVLEILDDRR--QWWKVRNASGDSGFVPNNILDI 586
Cdd:cd11896    2 ARALYSFQSENKEEINIQENEELVIFSENSldGWLQGQNSRGETGLFPASYVEI 55
SH3_Intersectin2_5 cd11996
Fifth Src homology 3 domain (or SH3E) of Intersectin-2; Intersectin-2 (ITSN2) is an adaptor ...
539-582 3.29e-03

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: 36.50  E-value: 3.29e-03
                         10        20        30        40
                 ....*....|....*....|....*....|....*....|....*
gi 409264659 539 YDFVARNSSELSVMKDDVLEILD-DRRQWWKvRNASGDSGFVPNN 582
Cdd:cd11996    7 YDYTANNEDELSFSKGQLINVLNkDDPDWWQ-GEINGVTGLFPSN 50
SH3_Srms cd11846
Src homology 3 domain of Srms Protein Tyrosine Kinase; Src-related kinase lacking C-terminal ...
539-582 4.56e-03

Src homology 3 domain of Srms Protein Tyrosine Kinase; Src-related kinase lacking C-terminal regulatory tyrosine and N-terminal myristoylation sites (Srms) is a cytoplasmic (or non-receptor) PTK with limited homology to Src kinases. 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, Srms lacks the N-terminal myristoylation sites. Src proteins are involved in signaling pathways that regulate cytokine and growth factor responses, cytoskeleton dynamics, cell proliferation, survival, and differentiation. 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: 212780  Cd Length: 55  Bit Score: 35.91  E-value: 4.56e-03
                         10        20        30        40
                 ....*....|....*....|....*....|....*....|....*.
gi 409264659 539 YDFVARNSSELSVMKDDVLEILDDRRQWWKVRNASGD--SGFVPNN 582
Cdd:cd11846    6 YDFTARSTHELSVEQGDKLCVIEEEGDYIFARKLTGNpeSGLVPAS 51
SH3_Sorbs_2 cd11782
Second Src Homology 3 domain of Sorbin and SH3 domain containing (Sorbs) proteins and similar ...
535-586 4.57e-03

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


Pssm-ID: 212716 [Multi-domain]  Cd Length: 53  Bit Score: 35.79  E-value: 4.57e-03
                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|....*
gi 409264659 535 AKSKYDFVARNSSELSVMKDDVLEILddRR---QWWKVRNAsGDSGFVPNNILDI 586
Cdd:cd11782    2 ARAKYNFNADTGVELSFRKGDVITLT--RRvdeNWYEGRIG-GRQGIFPVSYVQV 53
SH3_STAM cd11820
Src homology 3 domain of Signal Transducing Adaptor Molecules; STAMs were discovered as ...
536-582 4.68e-03

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


Pssm-ID: 212754 [Multi-domain]  Cd Length: 54  Bit Score: 35.90  E-value: 4.68e-03
                         10        20        30        40
                 ....*....|....*....|....*....|....*....|....*...
gi 409264659 536 KSKYDFVARNSSELSVMKDDVLEILDDRR-QWWKVRNASGdSGFVPNN 582
Cdd:cd11820    4 RALYDFEAAEDNELTFKAGEIITVLDDSDpNWWKGSNHRG-EGLFPAN 50
SH3_VAV3_2 cd11978
C-terminal (or second) Src homology 3 domain of VAV3 protein; VAV3 is ubiquitously expressed ...
535-585 4.89e-03

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: 36.16  E-value: 4.89e-03
                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|...
gi 409264659 535 AKSKYDFVARNSSELSVMKDDVLEILDDR--RQWWKvRNASGDSGFVPNNILD 585
Cdd:cd11978    3 AIARYDFCARDMRELSLLKGDVVKIYTKMstNGWWR-GEVNGRVGWFPSTYVE 54
 
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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