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Conserved domains on  [gi|1946280069|emb|CAD7441585|]
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unnamed protein product [Timema bartmani]

Protein Classification

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List of domain hits

 Name Accession Description Interval E-value
PH_Vav cd01223
Vav pleckstrin homology (PH) domain; Vav acts as a guanosine nucleotide exchange factor (GEF) ...
 568-694 1.33e-67

Vav pleckstrin homology (PH) domain; Vav acts as a guanosine nucleotide exchange factor (GEF) for Rho/Rac proteins. They control processes including T cell activation, phagocytosis, and migration of cells. The Vav subgroup of Dbl GEFs consists of three family members (Vav1, Vav2, and Vav3) in mammals. Vav1 is preferentially expressed in the hematopoietic system, while Vav2 and Vav3 are described by broader expression patterns. Mammalian Vav proteins consist of a calponin homology (CH) domain, an acidic region, a catalytic Dbl homology (DH) domain, a PH domain, a zinc finger cysteine rich domain (C1/CRD), and an SH2 domain, flanked by two SH3 domains. In invertebrates such as Drosophila and C. elegans, Vav is missing the N-terminal SH3 domain. The DH domain is involved in RhoGTPase recognition and selectivity and stimulates the reorganization of the switch regions for GDP/GTP exchange. The PH domain is implicated in directing membrane localization, allosteric regulation of guanine nucleotide exchange activity, and as a phospholipid- dependent regulator of GEF activity. Vavs bind RhoGTPases including Rac1, RhoA, RhoG, and Cdc42, while other members of the GEF family are specific for a single RhoGTPase. This promiscuity is thought to be a result of its CRD. PH domains have diverse functions, but in general are involved in targeting proteins to the appropriate cellular location or in the interaction with a binding partner. They share little sequence conservation, but all have a common fold, which is electrostatically polarized. Less than 10% of PH domains bind phosphoinositide phosphates (PIPs) with high affinity and specificity. PH domains are distinguished from other PIP-binding domains by their specific high-affinity binding to PIPs with two vicinal phosphate groups: PtdIns(3,4)P2, PtdIns(4,5)P2 or PtdIns(3,4,5)P3 which results in targeting some PH domain proteins to the plasma membrane. A few display strong specificity in lipid binding. Any specificity is usually determined by loop regions or insertions in the N-terminus of the domain, which are not conserved across all PH domains. PH domains are found in cellular signaling proteins such as serine/threonine kinase, tyrosine kinases, regulators of G-proteins, endocytotic GTPases, adaptors, as well as cytoskeletal associated molecules and in lipid associated enzymes.polarized. PH domains also have diverse functions. They are often involved in targeting proteins to the plasma membrane, but only a few (less than 10%) display strong specificity in binding inositol phosphates. Any specificity is usually determined by loop regions or insertions in the N-terminus of the domain, which are not conserved across all PH domains. PH domains are found in cellular signaling proteins such as serine/threonine kinases, tyrosine kinases, regulators of G-proteins, endocytotic GTPases, adaptors, cytoskeletal associated molecules, and in lipid associated enzymes.


:

Pssm-ID: 269930  Cd Length: 127  Bit Score: 222.51  E-value: 1.33e-67
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1946280069  568 SISDLDMPENTELKDYGRLLKDGELKIKAHDDQKIKTRYIFVFDQVIIMCKSLRGETYSYRESLRLQEYKIEDVHTRRTL 647
Cdd:cd01223      1 SIQDLIENLNESLADYGRLQIDGELKIKSHEDQKKKDRYAFLFDKVLLICKSLRGDQYEYKEIINLSEYRIEDDPSRRTL 80

                           90       100       110       120
                   ....*....|....*....|....*....|....*....|....*..
gi 1946280069  648 RTDARWSYQFYLVRKSERTAYTLYARTEDNKRKWMKAIHDAMDNLEP 694
Cdd:cd01223     81 KRDKRWSYQFLLVHKQGKTAYTLYAKTEELKKKWMEAIEMALSNIEP 127
CH_VAV cd21201
calponin homology (CH) domain found in VAV proteins; VAV proteins function both as cytoplasmic ...
 16-132 4.47e-49

calponin homology (CH) domain found in VAV proteins; VAV proteins function both as cytoplasmic guanine nucleotide exchange factors (GEFs) for Rho GTPases and as 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. This model corresponds to the CH domain, an actin-binding domain which is present as a single copy in VAV proteins.


:

Pssm-ID: 409050  Cd Length: 117  Bit Score: 169.74  E-value: 4.47e-49
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1946280069   16 ESWKECVEWLTRCDVLRRDHKTNWPEASVIDLANTLRDGVLLCNLLNVLDPGCIDLKDVNQKPQLAQFLCLRNIKTFLQT 95
Cdd:cd21201      1 ELWRQCADWLIRCGVLPPDHRATQPNATVFDLAQALRDGVLLCQLLNRLSPGSVDDREINLRPQMSQFLCLKNIRTFLQA 80

                           90       100       110
                   ....*....|....*....|....*....|....*..
gi 1946280069   96 CHDIFGLKENDLFEPSMLFELNDFFKVLNTLSKLSNC 132
Cdd:cd21201     81 CRTVFGLRSADLFEPEDLYDVTNFGKVIRTLSKLSHT 117
SH2 super family cl15255
Src homology 2 (SH2) domain; In general, SH2 domains are involved in signal transduction; they ...
 826-934 7.41e-42

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


The actual alignment was detected with superfamily member cd09940:

Pssm-ID: 472789  Cd Length: 102  Bit Score: 148.21  E-value: 7.41e-42
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1946280069  826 LKDHLWFVGEMGRDRASALLERHMDGTYLLRVRPQGathpnETIYALSLKTDDRVKHMKVYERTMEGvphYFLSESRFFR 905
Cdd:cd09940      2 LSEFLWFVGEMERDTAENRLENRPDGTYLVRVRPQG-----ETQYALSIKYNGDVKHMKIEQRSDGL---YYLSESRHFK 73

                           90       100
                   ....*....|....*....|....*....
gi 1946280069  906 SITDLIGCYEHSSLGENFVGLDVTLKWPF 934
Cdd:cd09940     74 SLVELVNYYERNSLGENFAGLDTTLKWPY 102
RhoGEF pfam00621
RhoGEF domain; Guanine nucleotide exchange factor for Rho/Rac/Cdc42-like GTPases Also called ...
 333-536 4.90e-38

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


:

Pssm-ID: 459876 [Multi-domain]  Cd Length: 176  Bit Score: 140.13  E-value: 4.90e-38
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1946280069  333 VIKELIETEKNYVDVLATVQRSFMRPLSSFIR--EEDMKAIFSGMKELSEIH-SGFHSHLRKAvaPNSSTRLSDVFINWR 409
Cdd:pfam00621    1 VIKELLQTERSYVRDLEILVEVFLPPNSKPLSesEEEIKTIFSNIEEIYELHrQLLLEELLKE--WISIQRIGDIFLKFA 78

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1946280069  410 EKFLIYGEYCAHLTSAQELIQDLCSRNEVVNQQVIKCQEEANGGKFKLRDILSVPMQRILKYHLLLDKLIQETQPsqehq 489
Cdd:pfam00621   79 PGFKVYSTYCSNYPKALKLLKKLLKKNPKFRAFLEELEANPECRGLDLNSFLIKPVQRIPRYPLLLKELLKHTPP----- 153

                          170       180       190       200
                   ....*....|....*....|....*....|....*....|....*..
gi 1946280069  490 gaslelqgvpfrvkitkelvwsyrSHEDYRGLERAKEAMVDVAQYIN 536
Cdd:pfam00621  154 ------------------------DHPDYEDLKKALEAIKEVAKQIN 176
C1_VAV cd20810
protein kinase C conserved region 1 (C1 domain) found in VAV proteins; VAV proteins function ...
 760-799 3.00e-15

protein kinase C conserved region 1 (C1 domain) found in VAV proteins; VAV proteins function both as cytoplasmic guanine nucleotide exchange factors (GEFs) for Rho GTPases and as 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. This model corresponds to the C1 domain. The C1 domain is a cysteine-rich zinc binding domain that does not bind DNA nor possess structural similarity to conventional zinc finger domains; it contains two separate Zn(2+)-binding sites.


:

Pssm-ID: 410360  Cd Length: 52  Bit Score: 70.75  E-value: 3.00e-15
                           10        20        30        40
                   ....*....|....*....|....*....|....*....|
gi 1946280069  760 ATTCHHCSKFLKGIILQGYLCGECSIAVHKQCIEFSGRCH 799
Cdd:cd20810     13 PTTCSVCKKLLKGLFFQGYKCSVCGAAVHKECIAKVKRCG 52
SH3 super family cl17036
Src Homology 3 domain superfamily; Src Homology 3 (SH3) domains are protein interaction ...
 938-992 6.52e-13

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.


The actual alignment was detected with superfamily member cd11766:

Pssm-ID: 473055 [Multi-domain]  Cd Length: 53  Bit Score: 64.21  E-value: 6.52e-13
                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....*
gi 1946280069  938 IAIAEFDFNPSESNQLPLRKGCQVIVLSKEGDykGWWKGKVQDRVGFFPKDYVRE 992
Cdd:cd11766      1 PAVVKFNYEAQREDELSLRKGDRVLVLEKSSD--GWWRGECNGQVGWFPSNYVTE 53
C1 super family cl00040
protein kinase C conserved region 1 (C1 domain) superfamily; The C1 domain is a cysteine-rich ...
 702-735 7.92e-04

protein kinase C conserved region 1 (C1 domain) superfamily; The C1 domain is a cysteine-rich zinc binding domain that does not bind DNA nor possess structural similarity to conventional zinc finger domains. It contains the motif HX12CX2CXnCX2CX4HX2CX7C, where C and H are cysteine and histidine, respectively; X represents other residues; and n is either 13 or 14. C1 has a globular fold with two separate Zn(2+)-binding sites. It was originally discovered as lipid-binding modules in protein kinase C (PKC) isoforms. C1 domains that bind and respond to phorbol esters (PE) and diacylglycerol (DAG) are referred to as typical, and those that do not respond to PE and DAG are deemed atypical. A C1 domain may also be referred to as PKC or non-PKC C1, based on the parent protein's activity. Most C1 domain-containing non-PKC proteins act as lipid kinases and scaffolds, except PKD which acts as a protein kinase. PKC C1 domains play roles in membrane translocation and activation of the enzyme.


The actual alignment was detected with superfamily member cd20803:

Pssm-ID: 412127  Cd Length: 56  Bit Score: 38.44  E-value: 7.92e-04
                           10        20        30
                   ....*....|....*....|....*....|....*..
gi 1946280069  702 HTFKMNTFEQATTCHHCSKFLKGIILQ--VCT-CRYV 735
Cdd:cd20803      2 HSFRKKTFHKPTYCHHCTDLLWGLLNQgyQCEvCNFV 38
 
Name Accession Description Interval E-value
PH_Vav cd01223
Vav pleckstrin homology (PH) domain; Vav acts as a guanosine nucleotide exchange factor (GEF) ...
 568-694 1.33e-67

Vav pleckstrin homology (PH) domain; Vav acts as a guanosine nucleotide exchange factor (GEF) for Rho/Rac proteins. They control processes including T cell activation, phagocytosis, and migration of cells. The Vav subgroup of Dbl GEFs consists of three family members (Vav1, Vav2, and Vav3) in mammals. Vav1 is preferentially expressed in the hematopoietic system, while Vav2 and Vav3 are described by broader expression patterns. Mammalian Vav proteins consist of a calponin homology (CH) domain, an acidic region, a catalytic Dbl homology (DH) domain, a PH domain, a zinc finger cysteine rich domain (C1/CRD), and an SH2 domain, flanked by two SH3 domains. In invertebrates such as Drosophila and C. elegans, Vav is missing the N-terminal SH3 domain. The DH domain is involved in RhoGTPase recognition and selectivity and stimulates the reorganization of the switch regions for GDP/GTP exchange. The PH domain is implicated in directing membrane localization, allosteric regulation of guanine nucleotide exchange activity, and as a phospholipid- dependent regulator of GEF activity. Vavs bind RhoGTPases including Rac1, RhoA, RhoG, and Cdc42, while other members of the GEF family are specific for a single RhoGTPase. This promiscuity is thought to be a result of its CRD. PH domains have diverse functions, but in general are involved in targeting proteins to the appropriate cellular location or in the interaction with a binding partner. They share little sequence conservation, but all have a common fold, which is electrostatically polarized. Less than 10% of PH domains bind phosphoinositide phosphates (PIPs) with high affinity and specificity. PH domains are distinguished from other PIP-binding domains by their specific high-affinity binding to PIPs with two vicinal phosphate groups: PtdIns(3,4)P2, PtdIns(4,5)P2 or PtdIns(3,4,5)P3 which results in targeting some PH domain proteins to the plasma membrane. A few display strong specificity in lipid binding. Any specificity is usually determined by loop regions or insertions in the N-terminus of the domain, which are not conserved across all PH domains. PH domains are found in cellular signaling proteins such as serine/threonine kinase, tyrosine kinases, regulators of G-proteins, endocytotic GTPases, adaptors, as well as cytoskeletal associated molecules and in lipid associated enzymes.polarized. PH domains also have diverse functions. They are often involved in targeting proteins to the plasma membrane, but only a few (less than 10%) display strong specificity in binding inositol phosphates. Any specificity is usually determined by loop regions or insertions in the N-terminus of the domain, which are not conserved across all PH domains. PH domains are found in cellular signaling proteins such as serine/threonine kinases, tyrosine kinases, regulators of G-proteins, endocytotic GTPases, adaptors, cytoskeletal associated molecules, and in lipid associated enzymes.


Pssm-ID: 269930  Cd Length: 127  Bit Score: 222.51  E-value: 1.33e-67
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1946280069  568 SISDLDMPENTELKDYGRLLKDGELKIKAHDDQKIKTRYIFVFDQVIIMCKSLRGETYSYRESLRLQEYKIEDVHTRRTL 647
Cdd:cd01223      1 SIQDLIENLNESLADYGRLQIDGELKIKSHEDQKKKDRYAFLFDKVLLICKSLRGDQYEYKEIINLSEYRIEDDPSRRTL 80

                           90       100       110       120
                   ....*....|....*....|....*....|....*....|....*..
gi 1946280069  648 RTDARWSYQFYLVRKSERTAYTLYARTEDNKRKWMKAIHDAMDNLEP 694
Cdd:cd01223     81 KRDKRWSYQFLLVHKQGKTAYTLYAKTEELKKKWMEAIEMALSNIEP 127
CH_VAV cd21201
calponin homology (CH) domain found in VAV proteins; VAV proteins function both as cytoplasmic ...
 16-132 4.47e-49

calponin homology (CH) domain found in VAV proteins; VAV proteins function both as cytoplasmic guanine nucleotide exchange factors (GEFs) for Rho GTPases and as 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. This model corresponds to the CH domain, an actin-binding domain which is present as a single copy in VAV proteins.


Pssm-ID: 409050  Cd Length: 117  Bit Score: 169.74  E-value: 4.47e-49
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1946280069   16 ESWKECVEWLTRCDVLRRDHKTNWPEASVIDLANTLRDGVLLCNLLNVLDPGCIDLKDVNQKPQLAQFLCLRNIKTFLQT 95
Cdd:cd21201      1 ELWRQCADWLIRCGVLPPDHRATQPNATVFDLAQALRDGVLLCQLLNRLSPGSVDDREINLRPQMSQFLCLKNIRTFLQA 80

                           90       100       110
                   ....*....|....*....|....*....|....*..
gi 1946280069   96 CHDIFGLKENDLFEPSMLFELNDFFKVLNTLSKLSNC 132
Cdd:cd21201     81 CRTVFGLRSADLFEPEDLYDVTNFGKVIRTLSKLSHT 117
SH2_Vav_family cd09940
Src homology 2 (SH2) domain found in the Vav family; Vav proteins are involved in several ...
 826-934 7.41e-42

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


Pssm-ID: 198193  Cd Length: 102  Bit Score: 148.21  E-value: 7.41e-42
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1946280069  826 LKDHLWFVGEMGRDRASALLERHMDGTYLLRVRPQGathpnETIYALSLKTDDRVKHMKVYERTMEGvphYFLSESRFFR 905
Cdd:cd09940      2 LSEFLWFVGEMERDTAENRLENRPDGTYLVRVRPQG-----ETQYALSIKYNGDVKHMKIEQRSDGL---YYLSESRHFK 73

                           90       100
                   ....*....|....*....|....*....
gi 1946280069  906 SITDLIGCYEHSSLGENFVGLDVTLKWPF 934
Cdd:cd09940     74 SLVELVNYYERNSLGENFAGLDTTLKWPY 102
RhoGEF pfam00621
RhoGEF domain; Guanine nucleotide exchange factor for Rho/Rac/Cdc42-like GTPases Also called ...
 333-536 4.90e-38

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


Pssm-ID: 459876 [Multi-domain]  Cd Length: 176  Bit Score: 140.13  E-value: 4.90e-38
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1946280069  333 VIKELIETEKNYVDVLATVQRSFMRPLSSFIR--EEDMKAIFSGMKELSEIH-SGFHSHLRKAvaPNSSTRLSDVFINWR 409
Cdd:pfam00621    1 VIKELLQTERSYVRDLEILVEVFLPPNSKPLSesEEEIKTIFSNIEEIYELHrQLLLEELLKE--WISIQRIGDIFLKFA 78

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1946280069  410 EKFLIYGEYCAHLTSAQELIQDLCSRNEVVNQQVIKCQEEANGGKFKLRDILSVPMQRILKYHLLLDKLIQETQPsqehq 489
Cdd:pfam00621   79 PGFKVYSTYCSNYPKALKLLKKLLKKNPKFRAFLEELEANPECRGLDLNSFLIKPVQRIPRYPLLLKELLKHTPP----- 153

                          170       180       190       200
                   ....*....|....*....|....*....|....*....|....*..
gi 1946280069  490 gaslelqgvpfrvkitkelvwsyrSHEDYRGLERAKEAMVDVAQYIN 536
Cdd:pfam00621  154 ------------------------DHPDYEDLKKALEAIKEVAKQIN 176
RhoGEF smart00325
Guanine nucleotide exchange factor for Rho/Rac/Cdc42-like GTPases; Guanine nucleotide exchange ...
 333-537 3.74e-36

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


Pssm-ID: 214619 [Multi-domain]  Cd Length: 180  Bit Score: 135.12  E-value: 3.74e-36
                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1946280069   333 VIKELIETEKNYVDVLATVQRSFMRPL---SSFIREEDMKAIFSGMKELSEIHSGFHSHLRKAVA--PNSSTRLSDVFIN 407
Cdd:smart00325    1 VLKELLQTERNYVRDLKLLVEVFLKPLkkeLKLLSPNELETLFGNIEEIYEFHRDFLDELEERIEewDDSVERIGDVFLK 80

                            90       100       110       120       130       140       150       160
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1946280069   408 WREKFLIYGEYCAHLTSAQELIQDLCSRNEVvnQQVIK-CQEEANGGKFKLRDILSVPMQRILKYHLLLDKLIQETQPsq 486
Cdd:smart00325   81 LEEFFKIYSEYCSNHPDALELLKKLKKNPRF--QKFLKeIESSPQCRRLTLESLLLKPVQRLTKYPLLLKELLKHTPE-- 156

                           170       180       190       200       210
                    ....*....|....*....|....*....|....*....|....*....|.
gi 1946280069   487 ehqgaslelqgvpfrvkitkelvwsyrSHEDYRGLERAKEAMVDVAQYINE 537
Cdd:smart00325  157 ---------------------------DHEDREDLKKALKAIKELANQVNE 180
RhoGEF cd00160
Guanine nucleotide exchange factor for Rho/Rac/Cdc42-like GTPases; Also called Dbl-homologous ...
 330-536 6.06e-35

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


Pssm-ID: 238091 [Multi-domain]  Cd Length: 181  Bit Score: 131.65  E-value: 6.06e-35
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1946280069  330 RDYVIKELIETEKNYVDVLATVQRSFMRPLSSFIR---EEDMKAIFSGMKELSEIHSGFHSHLRKAVA--PNSSTRLSDV 404
Cdd:cd00160      1 RQEVIKELLQTERNYVRDLKLLVEVFLKPLDKELLplsPEEVELLFGNIEEIYEFHRIFLKSLEERVEewDKSGPRIGDV 80

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1946280069  405 FINWREKFLIYGEYCAHLTSAQELIQDLCSRNEVVnQQVIKCQEEANGgKFKLRDILSVPMQRILKYHLLLDKLIQETQP 484
Cdd:cd00160     81 FLKLAPFFKIYSEYCSNHPDALELLKKLKKFNKFF-QEFLEKAESECG-RLKLESLLLKPVQRLTKYPLLLKELLKHTPD 158

                          170       180       190       200       210
                   ....*....|....*....|....*....|....*....|....*....|..
gi 1946280069  485 SqehqgaslelqgvpfrvkitkelvwsyrsHEDYRGLERAKEAMVDVAQYIN 536
Cdd:cd00160    159 G-----------------------------HEDREDLKKALEAIKEVASQVN 181
SH2 smart00252
Src homology 2 domains; Src homology 2 domains bind phosphotyrosine-containing polypeptides ...
 829-920 1.06e-15

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


Pssm-ID: 214585 [Multi-domain]  Cd Length: 84  Bit Score: 73.03  E-value: 1.06e-15
                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1946280069   829 HLWFVGEMGRDRASALLERHMDGTYLLRVRPQgatHPNEtiYALSLKTDDRVKHMKVyERTMEGVphYFLSESRFFRSIT 908
Cdd:smart00252    1 QPWYHGFISREEAEKLLKNEGDGDFLVRDSES---SPGD--YVLSVRVKGKVKHYRI-RRNEDGK--FYLEGGRKFPSLV 72

                            90
                    ....*....|..
gi 1946280069   909 DLIGCYEHSSLG 920
Cdd:smart00252   73 ELVEHYQKNSLG 84
C1_VAV cd20810
protein kinase C conserved region 1 (C1 domain) found in VAV proteins; VAV proteins function ...
 760-799 3.00e-15

protein kinase C conserved region 1 (C1 domain) found in VAV proteins; VAV proteins function both as cytoplasmic guanine nucleotide exchange factors (GEFs) for Rho GTPases and as 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. This model corresponds to the C1 domain. The C1 domain is a cysteine-rich zinc binding domain that does not bind DNA nor possess structural similarity to conventional zinc finger domains; it contains two separate Zn(2+)-binding sites.


Pssm-ID: 410360  Cd Length: 52  Bit Score: 70.75  E-value: 3.00e-15
                           10        20        30        40
                   ....*....|....*....|....*....|....*....|
gi 1946280069  760 ATTCHHCSKFLKGIILQGYLCGECSIAVHKQCIEFSGRCH 799
Cdd:cd20810     13 PTTCSVCKKLLKGLFFQGYKCSVCGAAVHKECIAKVKRCG 52
SH2 pfam00017
SH2 domain;
831-911 4.89e-13

SH2 domain;


Pssm-ID: 425423 [Multi-domain]  Cd Length: 77  Bit Score: 65.31  E-value: 4.89e-13
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1946280069  831 WFVGEMGRDRA-SALLERHMDGTYLLRvrpQGATHPNEtiYALSLKTDDRVKHMKVyERTMEGvpHYFLSESRFFRSITD 909
Cdd:pfam00017    1 WYHGKISRQEAeRLLLNGKPDGTFLVR---ESESTPGG--YTLSVRDDGKVKHYKI-QSTDNG--GYYISGGVKFSSLAE 72


                   ..
gi 1946280069  910 LI 911
Cdd:pfam00017   73 LV 74
SH3_Nck_2 cd11766
Second Src Homology 3 domain of Nck adaptor proteins; Nck adaptor proteins regulate actin ...
 938-992 6.52e-13

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


Pssm-ID: 212700 [Multi-domain]  Cd Length: 53  Bit Score: 64.21  E-value: 6.52e-13
                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....*
gi 1946280069  938 IAIAEFDFNPSESNQLPLRKGCQVIVLSKEGDykGWWKGKVQDRVGFFPKDYVRE 992
Cdd:cd11766      1 PAVVKFNYEAQREDELSLRKGDRVLVLEKSSD--GWWRGECNGQVGWFPSNYVTE 53
SH3 smart00326
Src homology 3 domains; Src homology 3 (SH3) domains bind to target proteins through sequences ...
 939-991 4.66e-11

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: 59.09  E-value: 4.66e-11
                            10        20        30        40        50
                    ....*....|....*....|....*....|....*....|....*....|....
gi 1946280069   939 AIAEFDFNPSESNQLPLRKGCQVIVLSKEGDykGWWKGKVQD-RVGFFPKDYVR 991
Cdd:smart00326    5 VRALYDYTAQDPDELSFKKGDIITVLEKSDD--GWWKGRLGRgKEGLFPSNYVE 56
PH pfam00169
PH domain; PH stands for pleckstrin homology.
 586-689 8.05e-11

PH domain; PH stands for pleckstrin homology.


Pssm-ID: 459697 [Multi-domain]  Cd Length: 105  Bit Score: 59.88  E-value: 8.05e-11
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1946280069  586 LLKDGELKIKAHDDQKI-KTRYIFVFDQVIIMCK-SLRGETYSYRESLRLQeyKIEDVHTRRTLRTDARWSYQFYLVRKS 663
Cdd:pfam00169    1 VVKEGWLLKKGGGKKKSwKKRYFVLFDGSLLYYKdDKSGKSKEPKGSISLS--GCEVVEVVASDSPKRKFCFELRTGERT 78

                           90       100
                   ....*....|....*....|....*.
gi 1946280069  664 ERTAYTLYARTEDNKRKWMKAIHDAM 689
Cdd:pfam00169   79 GKRTYLLQAESEEERKDWIKAIQSAI 104
CH pfam00307
Calponin homology (CH) domain; The CH domain is found in both cytoskeletal proteins and signal ...
 15-131 1.57e-10

Calponin homology (CH) domain; The CH domain is found in both cytoskeletal proteins and signal transduction proteins. The CH domain is involved in actin binding in some members of the family. However in calponins there is evidence that the CH domain is not involved in its actin binding activity. Most member proteins have from two to four copies of the CH domain, however some proteins such as calponin have only a single copy.


Pssm-ID: 425596 [Multi-domain]  Cd Length: 109  Bit Score: 59.22  E-value: 1.57e-10
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1946280069   15 NESWKECVEWLTRCDVLRRDHKtnwpeaSVIDLANTLRDGVLLCNLLNVLDPGCIDLKDVNQKPqlaqFLCLRNIKTFLQ 94
Cdd:pfam00307    1 LELEKELLRWINSHLAEYGPGV------RVTNFTTDLRDGLALCALLNKLAPGLVDKKKLNKSE----FDKLENINLALD 70

                           90       100       110
                   ....*....|....*....|....*....|....*..
gi 1946280069   95 TCHDIFGLKEnDLFEPSMLFELNDfFKVLNTLSKLSN 131
Cdd:pfam00307   71 VAEKKLGVPK-VLIEPEDLVEGDN-KSVLTYLASLFR 105
SH3_1 pfam00018
SH3 domain; SH3 (Src homology 3) domains are often indicative of a protein involved in signal ...
 940-986 3.02e-09

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: 53.75  E-value: 3.02e-09
                           10        20        30        40
                   ....*....|....*....|....*....|....*....|....*...
gi 1946280069  940 IAEFDFNPSESNQLPLRKGCQVIVLSKEGDykGWWKGKVQ-DRVGFFP 986
Cdd:pfam00018    1 VALYDYTAQEPDELSFKKGDIIIVLEKSED--GWWKGRNKgGKEGLIP 46
PH smart00233
Pleckstrin homology domain; Domain commonly found in eukaryotic signalling proteins. The ...
 586-690 7.08e-09

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


Pssm-ID: 214574 [Multi-domain]  Cd Length: 102  Bit Score: 54.48  E-value: 7.08e-09
                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1946280069   586 LLKDGELKIK-AHDDQKIKTRYIFVFDQVIIMCKS-LRGETYSYRESLRLQEYKIEDVHTRrtlrTDARWSYQFYLVRKS 663
Cdd:smart00233    1 VIKEGWLYKKsGGGKKSWKKRYFVLFNSTLLYYKSkKDKKSYKPKGSIDLSGCTVREAPDP----DSSKKPHCFEIKTSD 76

                            90       100
                    ....*....|....*....|....*..
gi 1946280069   664 ERTaYTLYARTEDNKRKWMKAIHDAMD 690
Cdd:smart00233   77 RKT-LLLQAESEEEREKWVEALRKAIA 102
C1 smart00109
Protein kinase C conserved region 1 (C1) domains (Cysteine-rich domains); Some bind phorbol ...
 752-794 2.57e-07

Protein kinase C conserved region 1 (C1) domains (Cysteine-rich domains); Some bind phorbol esters and diacylglycerol. Some bind RasGTP. Zinc-binding domains.


Pssm-ID: 197519  Cd Length: 50  Bit Score: 48.23  E-value: 2.57e-07
                            10        20        30        40
                    ....*....|....*....|....*....|....*....|...
gi 1946280069   752 YTPGMYLQATTCHHCSKFLKGIILQGYLCGECSIAVHKQCIEF 794
Cdd:smart00109    3 HVFRTFTKPTFCCVCRKSIWGSFKQGLRCSECKVKCHKKCADK 45
C1_1 pfam00130
Phorbol esters/diacylglycerol binding domain (C1 domain); This domain is also known as the ...
 757-794 6.00e-07

Phorbol esters/diacylglycerol binding domain (C1 domain); This domain is also known as the Protein kinase C conserved region 1 (C1) domain.


Pssm-ID: 395079  Cd Length: 53  Bit Score: 47.44  E-value: 6.00e-07
                           10        20        30
                   ....*....|....*....|....*....|....*...
gi 1946280069  757 YLQATTCHHCSKFLKGIILQGYLCGECSIAVHKQCIEF 794
Cdd:pfam00130    8 FKQPTFCDHCGEFLWGLGKQGLKCSWCKLNVHKRCHEK 45
CH smart00033
Calponin homology domain; Actin binding domains present in duplicate at the N-termini of ...
 19-129 5.09e-05

Calponin homology domain; Actin binding domains present in duplicate at the N-termini of spectrin-like proteins (including dystrophin, alpha-actinin). These domains cross-link actin filaments into bundles and networks. A calponin homology domain is predicted in yeasst Cdc24p.


Pssm-ID: 214479 [Multi-domain]  Cd Length: 101  Bit Score: 43.46  E-value: 5.09e-05
                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1946280069    19 KECVEWLtrcdvlrRDHKTNWPEASVIDLANTLRDGVLLCNLLNVLDPGCIDLKDVNqkPQLAQFLCLRNIKTFLQTCHD 98
Cdd:smart00033    1 KTLLRWV-------NSLLAEYDKPPVTNFSSDLKDGVALCALLNSLSPGLVDKKKVA--ASLSRFKKIENINLALSFAEK 71

                            90       100       110
                    ....*....|....*....|....*....|..
gi 1946280069    99 IFGlkENDLFEPSMLFE-LNDFFKVLNTLSKL 129
Cdd:smart00033   72 LGG--KVVLFEPEDLVEgPKLILGVIWTLISL 101
C1_DGKtheta_typeV_rpt1 cd20803
first protein kinase C conserved region 1 (C1 domain) found in type V diacylglycerol kinase, ...
 702-735 7.92e-04

first protein kinase C conserved region 1 (C1 domain) found in type V diacylglycerol kinase, DAG kinase theta, and similar proteins; Diacylglycerol (DAG) kinase (EC 2.7.1.107) is a lipid kinase that phosphorylates diacylglycerol to form phosphatidic acid. DAG kinase theta, also called diglyceride kinase theta (DGK-theta), is the only isoform classified as type V; it contains a pleckstrin homology (PH)-like domain and an additional C1 domain, compared to other DGKs. It may regulate the activity of protein kinase C by controlling the balance between the two signaling lipids, diacylglycerol and phosphatidic acid. DAG kinase theta contains three copies of the C1 domain. This model corresponds to the first one. The C1 domain is a cysteine-rich zinc binding domain that does not bind DNA nor possess structural similarity to conventional zinc finger domains; it contains two separate Zn(2+)-binding sites.


Pssm-ID: 410353  Cd Length: 56  Bit Score: 38.44  E-value: 7.92e-04
                           10        20        30
                   ....*....|....*....|....*....|....*..
gi 1946280069  702 HTFKMNTFEQATTCHHCSKFLKGIILQ--VCT-CRYV 735
Cdd:cd20803      2 HSFRKKTFHKPTYCHHCTDLLWGLLNQgyQCEvCNFV 38
 
Name Accession Description Interval E-value
PH_Vav cd01223
Vav pleckstrin homology (PH) domain; Vav acts as a guanosine nucleotide exchange factor (GEF) ...
 568-694 1.33e-67

Vav pleckstrin homology (PH) domain; Vav acts as a guanosine nucleotide exchange factor (GEF) for Rho/Rac proteins. They control processes including T cell activation, phagocytosis, and migration of cells. The Vav subgroup of Dbl GEFs consists of three family members (Vav1, Vav2, and Vav3) in mammals. Vav1 is preferentially expressed in the hematopoietic system, while Vav2 and Vav3 are described by broader expression patterns. Mammalian Vav proteins consist of a calponin homology (CH) domain, an acidic region, a catalytic Dbl homology (DH) domain, a PH domain, a zinc finger cysteine rich domain (C1/CRD), and an SH2 domain, flanked by two SH3 domains. In invertebrates such as Drosophila and C. elegans, Vav is missing the N-terminal SH3 domain. The DH domain is involved in RhoGTPase recognition and selectivity and stimulates the reorganization of the switch regions for GDP/GTP exchange. The PH domain is implicated in directing membrane localization, allosteric regulation of guanine nucleotide exchange activity, and as a phospholipid- dependent regulator of GEF activity. Vavs bind RhoGTPases including Rac1, RhoA, RhoG, and Cdc42, while other members of the GEF family are specific for a single RhoGTPase. This promiscuity is thought to be a result of its CRD. PH domains have diverse functions, but in general are involved in targeting proteins to the appropriate cellular location or in the interaction with a binding partner. They share little sequence conservation, but all have a common fold, which is electrostatically polarized. Less than 10% of PH domains bind phosphoinositide phosphates (PIPs) with high affinity and specificity. PH domains are distinguished from other PIP-binding domains by their specific high-affinity binding to PIPs with two vicinal phosphate groups: PtdIns(3,4)P2, PtdIns(4,5)P2 or PtdIns(3,4,5)P3 which results in targeting some PH domain proteins to the plasma membrane. A few display strong specificity in lipid binding. Any specificity is usually determined by loop regions or insertions in the N-terminus of the domain, which are not conserved across all PH domains. PH domains are found in cellular signaling proteins such as serine/threonine kinase, tyrosine kinases, regulators of G-proteins, endocytotic GTPases, adaptors, as well as cytoskeletal associated molecules and in lipid associated enzymes.polarized. PH domains also have diverse functions. They are often involved in targeting proteins to the plasma membrane, but only a few (less than 10%) display strong specificity in binding inositol phosphates. Any specificity is usually determined by loop regions or insertions in the N-terminus of the domain, which are not conserved across all PH domains. PH domains are found in cellular signaling proteins such as serine/threonine kinases, tyrosine kinases, regulators of G-proteins, endocytotic GTPases, adaptors, cytoskeletal associated molecules, and in lipid associated enzymes.


Pssm-ID: 269930  Cd Length: 127  Bit Score: 222.51  E-value: 1.33e-67
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1946280069  568 SISDLDMPENTELKDYGRLLKDGELKIKAHDDQKIKTRYIFVFDQVIIMCKSLRGETYSYRESLRLQEYKIEDVHTRRTL 647
Cdd:cd01223      1 SIQDLIENLNESLADYGRLQIDGELKIKSHEDQKKKDRYAFLFDKVLLICKSLRGDQYEYKEIINLSEYRIEDDPSRRTL 80

                           90       100       110       120
                   ....*....|....*....|....*....|....*....|....*..
gi 1946280069  648 RTDARWSYQFYLVRKSERTAYTLYARTEDNKRKWMKAIHDAMDNLEP 694
Cdd:cd01223     81 KRDKRWSYQFLLVHKQGKTAYTLYAKTEELKKKWMEAIEMALSNIEP 127
CH_VAV cd21201
calponin homology (CH) domain found in VAV proteins; VAV proteins function both as cytoplasmic ...
 16-132 4.47e-49

calponin homology (CH) domain found in VAV proteins; VAV proteins function both as cytoplasmic guanine nucleotide exchange factors (GEFs) for Rho GTPases and as 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. This model corresponds to the CH domain, an actin-binding domain which is present as a single copy in VAV proteins.


Pssm-ID: 409050  Cd Length: 117  Bit Score: 169.74  E-value: 4.47e-49
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1946280069   16 ESWKECVEWLTRCDVLRRDHKTNWPEASVIDLANTLRDGVLLCNLLNVLDPGCIDLKDVNQKPQLAQFLCLRNIKTFLQT 95
Cdd:cd21201      1 ELWRQCADWLIRCGVLPPDHRATQPNATVFDLAQALRDGVLLCQLLNRLSPGSVDDREINLRPQMSQFLCLKNIRTFLQA 80

                           90       100       110
                   ....*....|....*....|....*....|....*..
gi 1946280069   96 CHDIFGLKENDLFEPSMLFELNDFFKVLNTLSKLSNC 132
Cdd:cd21201     81 CRTVFGLRSADLFEPEDLYDVTNFGKVIRTLSKLSHT 117
SH2_Vav_family cd09940
Src homology 2 (SH2) domain found in the Vav family; Vav proteins are involved in several ...
 826-934 7.41e-42

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


Pssm-ID: 198193  Cd Length: 102  Bit Score: 148.21  E-value: 7.41e-42
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1946280069  826 LKDHLWFVGEMGRDRASALLERHMDGTYLLRVRPQGathpnETIYALSLKTDDRVKHMKVYERTMEGvphYFLSESRFFR 905
Cdd:cd09940      2 LSEFLWFVGEMERDTAENRLENRPDGTYLVRVRPQG-----ETQYALSIKYNGDVKHMKIEQRSDGL---YYLSESRHFK 73

                           90       100
                   ....*....|....*....|....*....
gi 1946280069  906 SITDLIGCYEHSSLGENFVGLDVTLKWPF 934
Cdd:cd09940     74 SLVELVNYYERNSLGENFAGLDTTLKWPY 102
RhoGEF pfam00621
RhoGEF domain; Guanine nucleotide exchange factor for Rho/Rac/Cdc42-like GTPases Also called ...
 333-536 4.90e-38

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


Pssm-ID: 459876 [Multi-domain]  Cd Length: 176  Bit Score: 140.13  E-value: 4.90e-38
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1946280069  333 VIKELIETEKNYVDVLATVQRSFMRPLSSFIR--EEDMKAIFSGMKELSEIH-SGFHSHLRKAvaPNSSTRLSDVFINWR 409
Cdd:pfam00621    1 VIKELLQTERSYVRDLEILVEVFLPPNSKPLSesEEEIKTIFSNIEEIYELHrQLLLEELLKE--WISIQRIGDIFLKFA 78

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1946280069  410 EKFLIYGEYCAHLTSAQELIQDLCSRNEVVNQQVIKCQEEANGGKFKLRDILSVPMQRILKYHLLLDKLIQETQPsqehq 489
Cdd:pfam00621   79 PGFKVYSTYCSNYPKALKLLKKLLKKNPKFRAFLEELEANPECRGLDLNSFLIKPVQRIPRYPLLLKELLKHTPP----- 153

                          170       180       190       200
                   ....*....|....*....|....*....|....*....|....*..
gi 1946280069  490 gaslelqgvpfrvkitkelvwsyrSHEDYRGLERAKEAMVDVAQYIN 536
Cdd:pfam00621  154 ------------------------DHPDYEDLKKALEAIKEVAKQIN 176
CH_VAV3 cd21264
calponin homology (CH) domain found in VAV3 protein and similar proteins; VAV3 is ubiquitously ...
 16-130 1.22e-37

calponin homology (CH) domain found in VAV3 protein and similar proteins; VAV3 is ubiquitously expressed and functions as a phosphorylation-dependent guanine nucleotide exchange factor (GEF) for RhoA, RhoG, and Rac1. Its function has been implicated 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 model corresponds to CH domain, an actin-binding domain which is present as a single copy in VAV3 protein.


Pssm-ID: 409113  Cd Length: 117  Bit Score: 137.02  E-value: 1.22e-37
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1946280069   16 ESWKECVEWLTRCDVLRRDHKTNWPEASVIDLANTLRDGVLLCNLLNVLDPGCIDLKDVNQKPQLAQFLCLRNIKTFLQT 95
Cdd:cd21264      1 EPWKQCAQWLIHCKVLPPNHRVTWDTAQVFDLAQTLRDGVLLCQLLNNLRPHSINLKEINLRPQMSQFLCLKNIRTFLSA 80

                           90       100       110
                   ....*....|....*....|....*....|....*
gi 1946280069   96 CHDIFGLKENDLFEPSMLFELNDFFKVLNTLSKLS 130
Cdd:cd21264     81 CCETFGMRKSELFEAFDLFDVRDFGKVIETLSKLS 115
RhoGEF smart00325
Guanine nucleotide exchange factor for Rho/Rac/Cdc42-like GTPases; Guanine nucleotide exchange ...
 333-537 3.74e-36

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


Pssm-ID: 214619 [Multi-domain]  Cd Length: 180  Bit Score: 135.12  E-value: 3.74e-36
                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1946280069   333 VIKELIETEKNYVDVLATVQRSFMRPL---SSFIREEDMKAIFSGMKELSEIHSGFHSHLRKAVA--PNSSTRLSDVFIN 407
Cdd:smart00325    1 VLKELLQTERNYVRDLKLLVEVFLKPLkkeLKLLSPNELETLFGNIEEIYEFHRDFLDELEERIEewDDSVERIGDVFLK 80

                            90       100       110       120       130       140       150       160
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1946280069   408 WREKFLIYGEYCAHLTSAQELIQDLCSRNEVvnQQVIK-CQEEANGGKFKLRDILSVPMQRILKYHLLLDKLIQETQPsq 486
Cdd:smart00325   81 LEEFFKIYSEYCSNHPDALELLKKLKKNPRF--QKFLKeIESSPQCRRLTLESLLLKPVQRLTKYPLLLKELLKHTPE-- 156

                           170       180       190       200       210
                    ....*....|....*....|....*....|....*....|....*....|.
gi 1946280069   487 ehqgaslelqgvpfrvkitkelvwsyrSHEDYRGLERAKEAMVDVAQYINE 537
Cdd:smart00325  157 ---------------------------DHEDREDLKKALKAIKELANQVNE 180
CH_VAV2 cd21263
calponin homology (CH) domain found in VAV2 protein and similar proteins; VAV2 is widely ...
 16-130 1.16e-35

calponin homology (CH) domain found in VAV2 protein and similar proteins; VAV2 is widely expressed and functions as a guanine nucleotide exchange factor (GEF) for RhoA, RhoB and RhoG and also activates Rac1 and Cdc42. It is implicated in many cellular and physiological functions including blood pressure control, eye development, neurite outgrowth and branching, EGFR endocytosis and degradation, and cell cluster morphology, among others. It has been reported to associate with Nek3. VAV proteins contain several domains that enable their function: N-terminal calponin homology (CH), acidic, RhoGEF (also called Dbl-homologous or DH), Pleckstrin Homology (PH), C1 (zinc finger), SH2, and two SH3 domains. The model corresponds to CH domain, an actin-binding domain which is present as a single copy in VAV2 protein.


Pssm-ID: 409112  Cd Length: 119  Bit Score: 131.23  E-value: 1.16e-35
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1946280069   16 ESWKECVEWLTRCDVLRRDHKTNWPEASVIDLANTLRDGVLLCNLLNVLDPGCIDLKDVNQKPQLAQFLCLRNIKTFLQT 95
Cdd:cd21263      1 EEWRQCGRWLIDCKVLPPNHRVVWPSAVVFDLAQALRDGVLLCQLLHNLSPGSIDLKDINFRPQMSQFLCLKNIRTFLKV 80

                           90       100       110
                   ....*....|....*....|....*....|....*
gi 1946280069   96 CHDIFGLKENDLFEPSMLFELNDFFKVLNTLSKLS 130
Cdd:cd21263     81 CHDKFGLRNSELFDPFDLFDVRDFGKVISALSRLS 115
RhoGEF cd00160
Guanine nucleotide exchange factor for Rho/Rac/Cdc42-like GTPases; Also called Dbl-homologous ...
 330-536 6.06e-35

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


Pssm-ID: 238091 [Multi-domain]  Cd Length: 181  Bit Score: 131.65  E-value: 6.06e-35
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1946280069  330 RDYVIKELIETEKNYVDVLATVQRSFMRPLSSFIR---EEDMKAIFSGMKELSEIHSGFHSHLRKAVA--PNSSTRLSDV 404
Cdd:cd00160      1 RQEVIKELLQTERNYVRDLKLLVEVFLKPLDKELLplsPEEVELLFGNIEEIYEFHRIFLKSLEERVEewDKSGPRIGDV 80

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1946280069  405 FINWREKFLIYGEYCAHLTSAQELIQDLCSRNEVVnQQVIKCQEEANGgKFKLRDILSVPMQRILKYHLLLDKLIQETQP 484
Cdd:cd00160     81 FLKLAPFFKIYSEYCSNHPDALELLKKLKKFNKFF-QEFLEKAESECG-RLKLESLLLKPVQRLTKYPLLLKELLKHTPD 158

                          170       180       190       200       210
                   ....*....|....*....|....*....|....*....|....*....|..
gi 1946280069  485 SqehqgaslelqgvpfrvkitkelvwsyrsHEDYRGLERAKEAMVDVAQYIN 536
Cdd:cd00160    159 G-----------------------------HEDREDLKKALEAIKEVASQVN 181
CH_VAV1 cd21262
calponin homology (CH) domain found in VAV1 protein; VAV1 is expressed predominantly in the ...
 16-130 9.17e-35

calponin homology (CH) domain found in 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. This model corresponds to the CH domain, an actin-binding domain which is present as a single copy in VAV1 protein.


Pssm-ID: 409111  Cd Length: 120  Bit Score: 128.91  E-value: 9.17e-35
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1946280069   16 ESWKECVEWLTRCDVLRRDHKTNWPEASVIDLANTLRDGVLLCNLLNVLDPGCIDLKDVNQKPQLAQFLCLRNIKTFLQT 95
Cdd:cd21262      1 ELWRQCAHWLIQCRVLPPNHRVTWDSAQVCDLAQALRDGVLLCQLLNNLLPHAVNLREINLRPQMSQFLCLKNIRTFLST 80

                           90       100       110
                   ....*....|....*....|....*....|....*
gi 1946280069   96 CHDIFGLKENDLFEPSMLFELNDFFKVLNTLSKLS 130
Cdd:cd21262     81 CCEKFGLRKSELFEAFDLFDVRDFGKVIDTLSILS 115
SH2_Vav2 cd10406
Src homology 2 (SH2) domain found in the Vav2 proteins; Proto-oncogene vav is a member of the ...
 831-935 7.09e-20

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


Pssm-ID: 198269  Cd Length: 103  Bit Score: 85.89  E-value: 7.09e-20
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1946280069  831 WFVGEMGRDRASALLERHMDGTYLLRVRPQGATHpnetiYALSLKTDDRVKHMKVYERtmEGVPHyfLSESRFFRSITDL 910
Cdd:cd10406      7 WFAGNMERQQTDNLLKSHASGTYLIRERPAEAER-----FAISIKFNDEVKHIKVVEK--DNWIH--ITEAKKFESLLEL 77

                           90       100
                   ....*....|....*....|....*
gi 1946280069  911 IGCYEHSSLGENFVGLDVTLKWPFR 935
Cdd:cd10406     78 VEYYQCHSLKESFKQLDTTLKYPYK 102
SH2_Vav1 cd10405
Src homology 2 (SH2) domain found in the Vav1 proteins; Proto-oncogene vav is a member of the ...
 826-935 9.20e-20

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


Pssm-ID: 198268  Cd Length: 103  Bit Score: 85.45  E-value: 9.20e-20
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1946280069  826 LKDHLWFVGEMGRDRASALLERHMDGTYLLRVRPQGATHpnetiYALSLKTDDRVKHMKVYerTMEGVphYFLSESRFFR 905
Cdd:cd10405      2 LSVHLWYAGPMERAGAESILANRSDGTYLVRQRVKDAAE-----FAISIKYNVEVKHIKIM--TAEGL--YRITEKKAFR 72

                           90       100       110
                   ....*....|....*....|....*....|
gi 1946280069  906 SITDLIGCYEHSSLGENFVGLDVTLKWPFR 935
Cdd:cd10405     73 GLTELVEFYQQNSLKDCFKSLDTTLQFPFK 102
SH2_Vav3 cd10407
Src homology 2 (SH2) domain found in the Vav3 proteins; Proto-oncogene vav is a member of the ...
 829-935 4.67e-17

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


Pssm-ID: 198270  Cd Length: 103  Bit Score: 77.74  E-value: 4.67e-17
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1946280069  829 HLWFVGEMGRDRASALLERHMDGTYLLRVRPQGATHpnetiYALSLKTDDRVKHMKVYERtmEGVPHyfLSESRFFRSIT 908
Cdd:cd10407      5 QPWYAGAMERLQAETELINRVNSTYLVRHRTKESGE-----YAISIKYNNEVKHIKILTR--DGFFH--IAENRKFKSLM 75

                           90       100
                   ....*....|....*....|....*..
gi 1946280069  909 DLIGCYEHSSLGENFVGLDVTLKWPFR 935
Cdd:cd10407     76 ELVEYYKHHSLKEGFRSLDTTLQFPYK 102
SH2 smart00252
Src homology 2 domains; Src homology 2 domains bind phosphotyrosine-containing polypeptides ...
 829-920 1.06e-15

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


Pssm-ID: 214585 [Multi-domain]  Cd Length: 84  Bit Score: 73.03  E-value: 1.06e-15
                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1946280069   829 HLWFVGEMGRDRASALLERHMDGTYLLRVRPQgatHPNEtiYALSLKTDDRVKHMKVyERTMEGVphYFLSESRFFRSIT 908
Cdd:smart00252    1 QPWYHGFISREEAEKLLKNEGDGDFLVRDSES---SPGD--YVLSVRVKGKVKHYRI-RRNEDGK--FYLEGGRKFPSLV 72

                            90
                    ....*....|..
gi 1946280069   909 DLIGCYEHSSLG 920
Cdd:smart00252   73 ELVEHYQKNSLG 84
C1_VAV cd20810
protein kinase C conserved region 1 (C1 domain) found in VAV proteins; VAV proteins function ...
 760-799 3.00e-15

protein kinase C conserved region 1 (C1 domain) found in VAV proteins; VAV proteins function both as cytoplasmic guanine nucleotide exchange factors (GEFs) for Rho GTPases and as 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. This model corresponds to the C1 domain. The C1 domain is a cysteine-rich zinc binding domain that does not bind DNA nor possess structural similarity to conventional zinc finger domains; it contains two separate Zn(2+)-binding sites.


Pssm-ID: 410360  Cd Length: 52  Bit Score: 70.75  E-value: 3.00e-15
                           10        20        30        40
                   ....*....|....*....|....*....|....*....|
gi 1946280069  760 ATTCHHCSKFLKGIILQGYLCGECSIAVHKQCIEFSGRCH 799
Cdd:cd20810     13 PTTCSVCKKLLKGLFFQGYKCSVCGAAVHKECIAKVKRCG 52
SH2 pfam00017
SH2 domain;
831-911 4.89e-13

SH2 domain;


Pssm-ID: 425423 [Multi-domain]  Cd Length: 77  Bit Score: 65.31  E-value: 4.89e-13
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1946280069  831 WFVGEMGRDRA-SALLERHMDGTYLLRvrpQGATHPNEtiYALSLKTDDRVKHMKVyERTMEGvpHYFLSESRFFRSITD 909
Cdd:pfam00017    1 WYHGKISRQEAeRLLLNGKPDGTFLVR---ESESTPGG--YTLSVRDDGKVKHYKI-QSTDNG--GYYISGGVKFSSLAE 72


                   ..
gi 1946280069  910 LI 911
Cdd:pfam00017   73 LV 74
SH3_Nck_2 cd11766
Second Src Homology 3 domain of Nck adaptor proteins; Nck adaptor proteins regulate actin ...
 938-992 6.52e-13

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


Pssm-ID: 212700 [Multi-domain]  Cd Length: 53  Bit Score: 64.21  E-value: 6.52e-13
                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....*
gi 1946280069  938 IAIAEFDFNPSESNQLPLRKGCQVIVLSKEGDykGWWKGKVQDRVGFFPKDYVRE 992
Cdd:cd11766      1 PAVVKFNYEAQREDELSLRKGDRVLVLEKSSD--GWWRGECNGQVGWFPSNYVTE 53
SH3_MLK1-3 cd12059
Src Homology 3 domain of Mixed Lineage Kinases 1, 2, and 3; MLKs 1, 2, and 3 are Serine ...
 941-991 1.30e-12

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


Pssm-ID: 212992 [Multi-domain]  Cd Length: 58  Bit Score: 63.63  E-value: 1.30e-12
                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....*
gi 1946280069  941 AEFDFNPSESNQLPLRKGCQVIVLSKE----GDyKGWWKGKVQDRVGFFPKDYVR 991
Cdd:cd12059      4 AVFDYEASAEDELTLRRGDRVEVLSKDsavsGD-EGWWTGKINDRVGIFPSNYVT 57
SH3_MLK cd11876
Src Homology 3 domain of Mixed Lineage Kinases; MLKs are Serine/Threonine Kinases (STKs), ...
 941-992 9.45e-12

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


Pssm-ID: 212809 [Multi-domain]  Cd Length: 58  Bit Score: 60.99  E-value: 9.45e-12
                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....*.
gi 1946280069  941 AEFDFNPSESNQLPLRKGCQVIVLSKE----GDyKGWWKGKVQDRVGFFPKDYVRE 992
Cdd:cd11876      4 ALFDYDARGEDELTLRRGQPVEVLSKDaavsGD-EGWWTGKIGDKVGIFPSNYVAP 58
SH3 cd00174
Src Homology 3 domain superfamily; Src Homology 3 (SH3) domains are protein interaction ...
 938-989 1.98e-11

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: 59.78  E-value: 1.98e-11
                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|...
gi 1946280069  938 IAIAEFDFNPSESNQLPLRKGCQVIVLSKEGDykGWWKGKVQD-RVGFFPKDY 989
Cdd:cd00174      1 YARALYDYEAQDDDELSFKKGDIITVLEKDDD--GWWEGELNGgREGLFPANY 51
SH3_VAV_2 cd11830
C-terminal (or second) Src homology 3 domain of VAV proteins; VAV proteins function both as ...
 938-992 2.17e-11

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: 59.95  E-value: 2.17e-11
                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....*
gi 1946280069  938 IAIAEFDFNPSESNQLPLRKGCQVIVLSKEGDyKGWWKGKVQDRVGFFPKDYVRE 992
Cdd:cd11830      1 TAKARYDFCARDMRELSLKEGDVVKIYNKKGQ-QGWWRGEINGRIGWFPSTYVEE 54
SH3 smart00326
Src homology 3 domains; Src homology 3 (SH3) domains bind to target proteins through sequences ...
 939-991 4.66e-11

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: 59.09  E-value: 4.66e-11
                            10        20        30        40        50
                    ....*....|....*....|....*....|....*....|....*....|....
gi 1946280069   939 AIAEFDFNPSESNQLPLRKGCQVIVLSKEGDykGWWKGKVQD-RVGFFPKDYVR 991
Cdd:smart00326    5 VRALYDYTAQDPDELSFKKGDIITVLEKSDD--GWWKGRLGRgKEGLFPSNYVE 56
PH pfam00169
PH domain; PH stands for pleckstrin homology.
 586-689 8.05e-11

PH domain; PH stands for pleckstrin homology.


Pssm-ID: 459697 [Multi-domain]  Cd Length: 105  Bit Score: 59.88  E-value: 8.05e-11
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1946280069  586 LLKDGELKIKAHDDQKI-KTRYIFVFDQVIIMCK-SLRGETYSYRESLRLQeyKIEDVHTRRTLRTDARWSYQFYLVRKS 663
Cdd:pfam00169    1 VVKEGWLLKKGGGKKKSwKKRYFVLFDGSLLYYKdDKSGKSKEPKGSISLS--GCEVVEVVASDSPKRKFCFELRTGERT 78

                           90       100
                   ....*....|....*....|....*.
gi 1946280069  664 ERTAYTLYARTEDNKRKWMKAIHDAM 689
Cdd:pfam00169   79 GKRTYLLQAESEEERKDWIKAIQSAI 104
SH3_Ysc84p_like cd11842
Src homology 3 domain of Ysc84p and similar fungal proteins; This family is composed of the ...
 939-992 1.19e-10

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


Pssm-ID: 212776 [Multi-domain]  Cd Length: 55  Bit Score: 57.82  E-value: 1.19e-10
                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....
gi 1946280069  939 AIAEFDFNPSESNQLPLRKGCQVIVLSKEGDYKGWWKGKVQDRVGFFPKDYVRE 992
Cdd:cd11842      2 AVALYDFAGEQPGDLAFQKGDIITILKKSDSQNDWWTGRIGGREGIFPANYVEL 55
SH3_CD2AP-like_3 cd11875
Third Src Homology 3 domain (SH3C) of CD2-associated protein and similar proteins; This ...
 943-990 1.22e-10

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


Pssm-ID: 212808 [Multi-domain]  Cd Length: 55  Bit Score: 57.75  E-value: 1.22e-10
                           10        20        30        40
                   ....*....|....*....|....*....|....*....|....*...
gi 1946280069  943 FDFNPSESNQLPLRKGCQVIVLSKEGDYKGWWKGKVQDRVGFFPKDYV 990
Cdd:cd11875      6 FDYEAENEDELTLREGDIVTILSKDCEDKGWWKGELNGKRGVFPDNFV 53
SH2 cd00173
Src homology 2 (SH2) domain; In general, SH2 domains are involved in signal transduction; they ...
 831-911 1.51e-10

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


Pssm-ID: 198173 [Multi-domain]  Cd Length: 79  Bit Score: 58.24  E-value: 1.51e-10
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1946280069  831 WFVGEMGRDRASALLERHMDGTYLLRVRPqgaTHPNEtiYALSLKTD-DRVKHMKVyeRTMEGVPHYFLSESRFFRSITD 909
Cdd:cd00173      2 WFHGSISREEAERLLRGKPDGTFLVRESS---SEPGD--YVLSVRSGdGKVKHYLI--ERNEGGYYLLGGSGRTFPSLPE 74


                   ..
gi 1946280069  910 LI 911
Cdd:cd00173     75 LV 76
SH3_GRB2_like_C cd11805
C-terminal Src homology 3 domain of Growth factor receptor-bound protein 2 (GRB2) and related ...
 941-990 1.56e-10

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


Pssm-ID: 212739 [Multi-domain]  Cd Length: 53  Bit Score: 57.25  E-value: 1.56e-10
                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|
gi 1946280069  941 AEFDFNPSESNQLPLRKGCQVIVLSKegDYKGWWKGKVQDRVGFFPKDYV 990
Cdd:cd11805      4 ALYDFNPQEPGELEFRRGDIITVLDS--SDPDWWKGELRGRVGIFPANYV 51
CH pfam00307
Calponin homology (CH) domain; The CH domain is found in both cytoskeletal proteins and signal ...
 15-131 1.57e-10

Calponin homology (CH) domain; The CH domain is found in both cytoskeletal proteins and signal transduction proteins. The CH domain is involved in actin binding in some members of the family. However in calponins there is evidence that the CH domain is not involved in its actin binding activity. Most member proteins have from two to four copies of the CH domain, however some proteins such as calponin have only a single copy.


Pssm-ID: 425596 [Multi-domain]  Cd Length: 109  Bit Score: 59.22  E-value: 1.57e-10
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1946280069   15 NESWKECVEWLTRCDVLRRDHKtnwpeaSVIDLANTLRDGVLLCNLLNVLDPGCIDLKDVNQKPqlaqFLCLRNIKTFLQ 94
Cdd:pfam00307    1 LELEKELLRWINSHLAEYGPGV------RVTNFTTDLRDGLALCALLNKLAPGLVDKKKLNKSE----FDKLENINLALD 70

                           90       100       110
                   ....*....|....*....|....*....|....*..
gi 1946280069   95 TCHDIFGLKEnDLFEPSMLFELNDfFKVLNTLSKLSN 131
Cdd:pfam00307   71 VAEKKLGVPK-VLIEPEDLVEGDN-KSVLTYLASLFR 105
SH3_D21-like cd12142
Src Homology 3 domain of SH3 domain-containing protein 21 (SH3D21) and similar proteins; ...
 943-990 2.02e-10

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


Pssm-ID: 213018 [Multi-domain]  Cd Length: 55  Bit Score: 57.09  E-value: 2.02e-10
                           10        20        30        40
                   ....*....|....*....|....*....|....*....|....*...
gi 1946280069  943 FDFNPSESNQLPLRKGCQVIVLSKEGDYKGWWKGKVQDRVGFFPKDYV 990
Cdd:cd12142      6 FDYNPVAPDELALKKGDVIEVISKETEDEGWWEGELNGRRGFFPDNFV 53
SH3_Stac2_C cd11985
C-terminal Src homology 3 domain of SH3 and cysteine-rich domain-containing protein 2 (Stac2); ...
 940-991 3.25e-10

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


Pssm-ID: 212918  Cd Length: 53  Bit Score: 56.49  E-value: 3.25e-10
                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|..
gi 1946280069  940 IAEFDFNPSESNQLPLRKGCQVIVLSKEGDykGWWKGKVQDRVGFFPKDYVR 991
Cdd:cd11985      3 VALYKFLPQENNDLPLQPGDRVMVVDDSNE--DWWKGKSGDRVGFFPANFVQ 52
SH3_VAV1_2 cd11976
C-terminal (or second) Src homology 3 domain of VAV1 protein; VAV1 is expressed predominantly ...
 938-992 4.89e-10

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: 56.11  E-value: 4.89e-10
                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....*
gi 1946280069  938 IAIAEFDFNPSESNQLPLRKGCQVIVLSKEGdYKGWWKGKVQDRVGFFPKDYVRE 992
Cdd:cd11976      1 TAKARYDFCARDRSELSLKEGDIIKILNKKG-QQGWWRGEIYGRVGWFPANYVEE 54
SH3_VAV3_2 cd11978
C-terminal (or second) Src homology 3 domain of VAV3 protein; VAV3 is ubiquitously expressed ...
 938-992 6.28e-10

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: 55.80  E-value: 6.28e-10
                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....*
gi 1946280069  938 IAIAEFDFNPSESNQLPLRKGCQVIVLSKEGDyKGWWKGKVQDRVGFFPKDYVRE 992
Cdd:cd11978      2 IAIARYDFCARDMRELSLLKGDVVKIYTKMST-NGWWRGEVNGRVGWFPSTYVEE 55
SH3_GRAP_C cd11951
C-terminal Src homology 3 domain of GRB2-related adaptor protein; GRAP is a GRB-2 like adaptor ...
 941-990 6.66e-10

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: 55.58  E-value: 6.66e-10
                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|
gi 1946280069  941 AEFDFNPSESNQLPLRKGCQVIVLSKEGDYkgWWKGKVQDRVGFFPKDYV 990
Cdd:cd11951      4 AQYDFSAEDPSQLSFRRGDIIEVLDCPDPN--WWRGRISGRVGFFPRNYV 51
CH_SF cd00014
calponin homology (CH) domain superfamily; CH domains are actin filament (F-actin) binding ...
 19-131 7.30e-10

calponin homology (CH) domain superfamily; CH domains are actin filament (F-actin) binding motifs, which may be present as a single copy or in tandem repeats (which increase binding affinity). They either function as autonomous actin binding motifs or serve a regulatory function. CH domains are found in cytoskeletal and signal transduction proteins, including actin-binding proteins like spectrin, alpha-actinin, dystrophin, utrophin, and fimbrin, as well as proteins essential for regulation of cell shape (cortexillins), and signaling proteins (Vav).


Pssm-ID: 409031 [Multi-domain]  Cd Length: 103  Bit Score: 56.96  E-value: 7.30e-10
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1946280069   19 KECVEWLtrCDVLRRDhktnwPEASVIDLANTLRDGVLLCNLLNVLDPGCIDLKdvnQKPQLAQFLCLRNIKTFLQTCHD 98
Cdd:cd00014      2 EELLKWI--NEVLGEE-----LPVSITDLFESLRDGVLLCKLINKLSPGSIPKI---NKKPKSPFKKRENINLFLNACKK 71

                           90       100       110
                   ....*....|....*....|....*....|...
gi 1946280069   99 IfGLKENDLFEPSMLFELNDFFKVLNTLSKLSN 131
Cdd:cd00014     72 L-GLPELDLFEPEDLYEKGNLKKVLGTLWALAL 103
C1_RASGRP cd20808
protein kinase C conserved region 1 (C1 domain) found in the RAS guanyl-releasing protein ...
 757-791 8.46e-10

protein kinase C conserved region 1 (C1 domain) found in the RAS guanyl-releasing protein (RASGRP) family; The RASGRP family includes RASGRP1-4. They function as cation-, usually calcium-, and diacylglycerol (DAG)-regulated nucleotide exchange factor activating Ras through the exchange of bound GDP for GTP. RASGRP1, also called calcium and DAG-regulated guanine nucleotide exchange factor II (CalDAG-GEFII) or Ras guanyl-releasing protein, activates the Erk/MAP kinase cascade and regulates T-cell/B-cell development, homeostasis and differentiation by coupling T-lymphocyte/B-lymphocyte antigen receptors to Ras. RASGRP1 also regulates NK cell cytotoxicity and ITAM-dependent cytokine production by activation of Ras-mediated ERK and JNK pathways. RASGRP2, also called calcium and DAG-regulated guanine nucleotide exchange factor I (CalDAG-GEFI), Cdc25-like protein (CDC25L), or F25B3.3 kinase-like protein, specifically activates Rap and may also activate other GTPases such as RRAS, RRAS2, NRAS, KRAS but not HRAS. RASGRP2 is involved in aggregation of platelets and adhesion of T-lymphocytes and neutrophils probably through inside-out integrin activation, as well as in the muscarinic acetylcholine receptor M1/CHRM1 signaling pathway. RASGRP3, also called calcium and DAG-regulated guanine nucleotide exchange factor III (CalDAG-GEFIII), or guanine nucleotide exchange factor for Rap1, is a guanine nucleotide-exchange factor activating H-Ras, R-Ras and Ras-associated protein-1/2. It functions as an important mediator of signaling downstream from receptor coupled phosphoinositide turnover in B and T cells. RASGRP4 may function in mast cell differentiation. The C1 domain is a cysteine-rich zinc binding domain that does not bind DNA nor possess structural similarity to conventional zinc finger domains; it contains two separate Zn(2+)-binding sites.


Pssm-ID: 410358  Cd Length: 52  Bit Score: 55.42  E-value: 8.46e-10
                           10        20        30
                   ....*....|....*....|....*....|....*
gi 1946280069  757 YLQATTCHHCSKFLKGIILQGYLCGECSIAVHKQC 791
Cdd:cd20808      9 YFKPTFCDHCTGLLWGLIKQGYKCKDCGINCHKHC 43
SH3_Stac_1 cd11833
First C-terminal Src homology 3 domain of SH3 and cysteine-rich domain-containing (Stac) ...
 940-990 1.19e-09

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


Pssm-ID: 212767 [Multi-domain]  Cd Length: 53  Bit Score: 54.82  E-value: 1.19e-09
                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|.
gi 1946280069  940 IAEFDFNPSESNQLPLRKGCQVIVLSKEGDykGWWKGKVQDRVGFFPKDYV 990
Cdd:cd11833      3 VALYKFKPQENEDLEMRPGDKITLLDDSNE--DWWKGKIEDRVGFFPANFV 51
SH2_cSH2_p85_like cd09930
C-terminal Src homology 2 (cSH2) domain found in p85; Phosphoinositide 3-kinases (PI3Ks) are ...
 824-933 2.00e-09

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


Pssm-ID: 198184  Cd Length: 104  Bit Score: 55.88  E-value: 2.00e-09
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1946280069  824 PSLKDHLWFVGEMGRDRASALLERHMDGTYLLRVRPQGAThpnetiYALSLKTDDRVKHMKVYErTMEGvpHYFLSESRF 903
Cdd:cd09930      1 PHHDERTWLVGDINRTQAEELLRGKPDGTFLIRESSTQGC------YACSVVCNGEVKHCVIYK-TETG--YGFAEPYNL 71

                           90       100       110
                   ....*....|....*....|....*....|
gi 1946280069  904 FRSITDLIGCYEHSSLGENFVGLDVTLKWP 933
Cdd:cd09930     72 YESLKELVLHYAHNSLEQHNDSLTVTLAYP 101
SH3_VAV2_2 cd11977
C-terminal (or second) Src homology 3 domain of VAV2 protein; VAV2 is widely expressed and ...
 939-992 2.14e-09

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


Pssm-ID: 212910 [Multi-domain]  Cd Length: 58  Bit Score: 54.25  E-value: 2.14e-09
                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....
gi 1946280069  939 AIAEFDFNPSESNQLPLRKGCQVIVLSKEGDYKGWWKGKVQDRVGFFPKDYVRE 992
Cdd:cd11977      3 AVARYNFAARDMRELSLREGDVVRIYSRIGGDQGWWKGETNGRIGWFPSTYVEE 56
SH3_1 pfam00018
SH3 domain; SH3 (Src homology 3) domains are often indicative of a protein involved in signal ...
 940-986 3.02e-09

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: 53.75  E-value: 3.02e-09
                           10        20        30        40
                   ....*....|....*....|....*....|....*....|....*...
gi 1946280069  940 IAEFDFNPSESNQLPLRKGCQVIVLSKEGDykGWWKGKVQ-DRVGFFP 986
Cdd:pfam00018    1 VALYDYTAQEPDELSFKKGDIIIVLEKSED--GWWKGRNKgGKEGLIP 46
SH3_MLK4 cd12058
Src Homology 3 domain of Mixed Lineage Kinase 4; MLK4 is a Serine/Threonine Kinase (STK), ...
 941-990 3.19e-09

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


Pssm-ID: 212991 [Multi-domain]  Cd Length: 58  Bit Score: 53.79  E-value: 3.19e-09
                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....
gi 1946280069  941 AEFDFNPSESNQLPLRKGCQVIVLSKE----GDyKGWWKGKVQDRVGFFPKDYV 990
Cdd:cd12058      4 ALYDYEASGEDELSLRRGDVVEVLSQDaavsGD-DGWWAGKIRHRLGIFPANYV 56
SH3_SH3YL1_like cd11841
Src homology 3 domain of SH3 domain containing Ysc84-like 1 (SH3YL1) protein; SH3YL1 localizes ...
 938-990 4.66e-09

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


Pssm-ID: 212775  Cd Length: 54  Bit Score: 53.16  E-value: 4.66e-09
                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|...
gi 1946280069  938 IAIAEFDFNPSESNQLPLRKGCQVIVLSKEGDYKGWWKGKVQDRVGFFPKDYV 990
Cdd:cd11841      1 EVTALYSFEGQQPCDLSFQAGDRITVLTRTDSQFDWWEGRLRGRVGIFPANYV 53
SH3_Pex13p_fungal cd11771
Src Homology 3 domain of fungal peroxisomal membrane protein Pex13p; Pex13p, located in the ...
 941-990 6.38e-09

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: 53.05  E-value: 6.38e-09
                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....*
gi 1946280069  941 AEFDFNPSE-SNQLPLRKGCQVIVLSK---EGDYKGWWKGKVQD-RVGFFPKDYV 990
Cdd:cd11771      4 ALYDFTPENpEMELSLKKGDIVAVLSKtdpLGRDSEWWKGRTRDgRIGWFPSNYV 58
PH smart00233
Pleckstrin homology domain; Domain commonly found in eukaryotic signalling proteins. The ...
 586-690 7.08e-09

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


Pssm-ID: 214574 [Multi-domain]  Cd Length: 102  Bit Score: 54.48  E-value: 7.08e-09
                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1946280069   586 LLKDGELKIK-AHDDQKIKTRYIFVFDQVIIMCKS-LRGETYSYRESLRLQEYKIEDVHTRrtlrTDARWSYQFYLVRKS 663
Cdd:smart00233    1 VIKEGWLYKKsGGGKKSWKKRYFVLFNSTLLYYKSkKDKKSYKPKGSIDLSGCTVREAPDP----DSSKKPHCFEIKTSD 76

                            90       100
                    ....*....|....*....|....*..
gi 1946280069   664 ERTaYTLYARTEDNKRKWMKAIHDAMD 690
Cdd:smart00233   77 RKT-LLLQAESEEEREKWVEALRKAIA 102
SH3_Nck1_2 cd11901
Second Src Homology 3 domain of Nck1 adaptor protein; Nck1 (also called Nckalpha) plays a ...
 939-992 7.52e-09

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


Pssm-ID: 212834 [Multi-domain]  Cd Length: 55  Bit Score: 52.73  E-value: 7.52e-09
                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....
gi 1946280069  939 AIAEFDFNPSESNQLPLRKGCQVIVLSKEGDykGWWKGKVQDRVGFFPKDYVRE 992
Cdd:cd11901      4 AYVKFNYTAEREDELSLVKGTKVIVMEKCSD--GWWRGSYNGQVGWFPSNYVTE 55
C1_ARHGEF-like cd20832
protein kinase C conserved region 1 (C1 domain) found in uncharacterized Rho guanine ...
 757-793 1.51e-08

protein kinase C conserved region 1 (C1 domain) found in uncharacterized Rho guanine nucleotide exchange factor (ARHGEF)-like proteins; The family includes a group of uncharacterized proteins that show high sequence similarity to vertebrate Rho guanine nucleotide exchange factors ARHGEF11 and ARHGEF12, which may play a role in the regulation of RhoA GTPase by guanine nucleotide-binding alpha-12 (GNA12) and alpha-13 (GNA13). Unlike typical ARHGEF11 and ARHGEF12, members of this family contain a C1 domain. This model corresponds to the C1 domain. The C1 domain is a cysteine-rich zinc binding domain that does not bind DNA nor possess structural similarity to conventional zinc finger domains; it contains two separate Zn(2+)-binding sites.


Pssm-ID: 410382  Cd Length: 53  Bit Score: 51.60  E-value: 1.51e-08
                           10        20        30
                   ....*....|....*....|....*....|....*..
gi 1946280069  757 YLQATTCHHCSKFLKGIILQGYLCGECSIAVHKQCIE 793
Cdd:cd20832      9 YYQVTFCNHCSGLLWGIGYQGYQCSDCEFNIHKQCIE 45
SH3_Sorbs_2 cd11782
Second Src Homology 3 domain of Sorbin and SH3 domain containing (Sorbs) proteins and similar ...
 939-990 1.90e-08

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: 51.58  E-value: 1.90e-08
                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|..
gi 1946280069  939 AIAEFDFNPSESNQLPLRKGcQVIVLSKEGDyKGWWKGKVQDRVGFFPKDYV 990
Cdd:cd11782      2 ARAKYNFNADTGVELSFRKG-DVITLTRRVD-ENWYEGRIGGRQGIFPVSYV 51
PH_Collybistin_ASEF cd01224
Collybistin/APC-stimulated guanine nucleotide exchange factor pleckstrin homology (PH) domain; ...
 586-687 2.50e-08

Collybistin/APC-stimulated guanine nucleotide exchange factor pleckstrin homology (PH) domain; Collybistin (also called PEM2) is homologous to the Dbl proteins ASEF (also called ARHGEF4/RhoGEF4) and SPATA13 (Spermatogenesis-associated protein 13; also called ASEF2). It activates CDC42 specifically and not any other Rho-family GTPases. Collybistin consists of an SH3 domain, followed by a RhoGEF/DH and PH domain. In Dbl proteins, the DH and PH domains catalyze the exchange of GDP for GTP in Rho GTPases, allowing them to signal to downstream effectors. It induces submembrane clustering of the receptor-associated peripheral membrane protein gephyrin, which is thought to form a scaffold underneath the postsynaptic membrane linking receptors to the cytoskeleton. It also acts as a tumor suppressor that links adenomatous polyposis coli (APC) protein, a negative regulator of the Wnt signaling pathway and promotes the phosphorylation and degradation of beta-catenin, to Cdc42. Autoinhibition of collybistin is accomplished by the binding of its SH3 domain with both the RhoGEF and PH domains to block access of Cdc42 to the GTPase-binding site. Inactivation promotes cancer progression. PH domains have diverse functions, but in general are involved in targeting proteins to the appropriate cellular location or in the interaction with a binding partner. They share little sequence conservation, but all have a common fold, which is electrostatically polarized. Less than 10% of PH domains bind phosphoinositide phosphates (PIPs) with high affinity and specificity. PH domains are distinguished from other PIP-binding domains by their specific high-affinity binding to PIPs with two vicinal phosphate groups: PtdIns(3,4)P2, PtdIns(4,5)P2 or PtdIns(3,4,5)P3 which results in targeting some PH domain proteins to the plasma membrane. A few display strong specificity in lipid binding. Any specificity is usually determined by loop regions or insertions in the N-terminus of the domain, which are not conserved across all PH domains. PH domains are found in cellular signaling proteins such as serine/threonine kinase, tyrosine kinases, regulators of G-proteins, endocytotic GTPases, adaptors, as well as cytoskeletal associated molecules and in lipid associated enzymes.


Pssm-ID: 269931  Cd Length: 138  Bit Score: 53.80  E-value: 2.50e-08
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1946280069  586 LLKDGEL-KIKAHddqKIKTRYIFVFDQVIIMCK--SLRGETYSYRESLRLQEYKIEDVhtrrtlrTDARWSYQFYLVR- 661
Cdd:cd01224     29 LIHSGELtKISAG---RAQERTFFLFDHQLVYCKkdLLRRKNYIYKGRIDTDNMEIEDL-------PDGKDDESGVTVKn 98

                           90       100       110
                   ....*....|....*....|....*....|..
gi 1946280069  662 ------KSERTAYTLYARTEDNKRKWMKAIHD 687
Cdd:cd01224     99 awkiynASKNKWYVLCAKSAEEKQRWLEAFAE 130
SH3_Intersectin2_3 cd11992
Third Src homology 3 domain (or SH3C) of Intersectin-2; Intersectin-2 (ITSN2) is an adaptor ...
 940-991 2.87e-08

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


Pssm-ID: 212925  Cd Length: 52  Bit Score: 51.16  E-value: 2.87e-08
                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|..
gi 1946280069  940 IAEFDFNPSESNQLPLRKGCQVIVLSKEGDykgWWKGKVQDRVGFFPKDYVR 991
Cdd:cd11992      3 IALYPYSSSEPGDLTFNEGEEILVTQKDGE---WWTGSIEDRTGIFPSNYVR 51
SH3_SKAP1-like cd11866
Src Homology 3 domain of Src Kinase-Associated Phosphoprotein 1 and similar proteins; This ...
 943-990 3.46e-08

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


Pssm-ID: 212800  Cd Length: 53  Bit Score: 50.89  E-value: 3.46e-08
                           10        20        30        40
                   ....*....|....*....|....*....|....*....|....*...
gi 1946280069  943 FDFNPSESNQLPLRKGCQVIVLSKEGDYKGWWKGKVQDRVGFFPKDYV 990
Cdd:cd11866      6 WDCSGNEPDELSFKRGDLIYIISKEYDSFGWWVGELNGKVGLVPKDYL 53
SH3_2 pfam07653
Variant SH3 domain; SH3 (Src homology 3) domains are often indicative of a protein involved in ...
 939-992 3.53e-08

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: 50.67  E-value: 3.53e-08
                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....
gi 1946280069  939 AIAEFDFNPSESNQLPLRKGCQVIVLSKEGDykGWWKGKVQDRVGFFPKDYVRE 992
Cdd:pfam07653    2 GRVIFDYVGTDKNGLTLKKGDVVKVLGKDND--GWWEGETGGRVGLVPSTAVEE 53
SH3_CIN85_1 cd12052
First Src Homology 3 domain (SH3A) of Cbl-interacting protein of 85 kDa; CIN85, also called ...
 939-992 3.96e-08

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


Pssm-ID: 212985 [Multi-domain]  Cd Length: 53  Bit Score: 50.66  E-value: 3.96e-08
                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....
gi 1946280069  939 AIAEFDFNPSESNQLPLRKGcQVIVLSKEGDyKGWWKGKVQDRVGFFPKDYVRE 992
Cdd:cd12052      2 AIVEFDYKAQHEDELTITVG-DIITKIKKDD-GGWWEGEIKGRRGLFPDNFVRE 53
SH2_N-SH2_PLC_gamma_like cd10341
N-terminal Src homology 2 (N-SH2) domain in Phospholipase C gamma; Phospholipase C gamma is a ...
 831-919 4.83e-08

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


Pssm-ID: 199829  Cd Length: 99  Bit Score: 51.97  E-value: 4.83e-08
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1946280069  831 WFVGEM--GRDRASALLERHM---DGTYLLRvrpQGATHPNEtiYALSLKTDDRVKHMKVYERTMEGVPHYFLSESRFFR 905
Cdd:cd10341      6 WFHGKLgdGRDEAEKLLLEYCeggDGTFLVR---ESETFVGD--YTLSFWRNGKVQHCRIRSRQENGEKKYYLTDNLVFD 80

                           90
                   ....*....|....
gi 1946280069  906 SITDLIGCYEHSSL 919
Cdd:cd10341     81 SLYELIDYYRQNPL 94
SH2_nSH2_p85_like cd09942
N-terminal Src homology 2 (nSH2) domain found in p85; Phosphoinositide 3-kinases (PI3Ks) are ...
 825-936 5.77e-08

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


Pssm-ID: 198195  Cd Length: 110  Bit Score: 51.94  E-value: 5.77e-08
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1946280069  825 SLKDHLWFVGEMGRDRASALLERHMDGTYLLRvrpQGATHPNEtiYALSLKTDDRVKHMKVYERtmEGvpHYFLSESRFF 904
Cdd:cd09942      3 SLQEAEWYWGDISREEVNEKMRDTPDGTFLVR---DASTMKGD--YTLTLRKGGNNKLIKIFHR--DG--KYGFSDPLTF 73

                           90       100       110
                   ....*....|....*....|....*....|..
gi 1946280069  905 RSITDLIGCYEHSSLGENFVGLDVTLKWPFRR 936
Cdd:cd09942     74 NSVVELINYYRNNSLAEYNRKLDVKLLYPVSR 105
C1_cPKC_nPKC_rpt1 cd20792
first protein kinase C conserved region 1 (C1 domain) found in classical (or conventional) ...
 759-794 6.74e-08

first protein kinase C conserved region 1 (C1 domain) found in classical (or conventional) protein kinase C (cPKC), novel protein kinase C (nPKC), and similar proteins; PKCs are classified into three groups (classical, atypical, and novel) depending on their mode of activation and the structural characteristics of their regulatory domains. PKCs undergo three phosphorylations in order to take mature forms. In addition, cPKCs depend on calcium, DAG (1,2-diacylglycerol), and in most cases, phosphatidylserine (PS) for activation. nPKCs are calcium-independent, but require DAG and PS for activity, while atypical PKCs (aPKCs) only require PS. PKCs phosphorylate and modify the activities of a wide variety of cellular proteins including receptors, enzymes, cytoskeletal proteins, transcription factors, and other kinases. They play a central role in signal transduction pathways that regulate cell migration and polarity, proliferation, differentiation, and apoptosis. This family includes classical PKCs (cPKCs) and novel PKCs (nPKCs). There are four cPKC isoforms (named alpha, betaI, betaII, and gamma) and four nPKC isoforms (delta, epsilon, eta, and theta). Members of this family contain two copies of the C1 domain. This model corresponds to the first one. The C1 domain is a cysteine-rich zinc binding domain that does not bind DNA nor possess structural similarity to conventional zinc finger domains; it contains two separate Zn(2+)-binding sites.


Pssm-ID: 410342  Cd Length: 53  Bit Score: 49.94  E-value: 6.74e-08
                           10        20        30
                   ....*....|....*....|....*....|....*.
gi 1946280069  759 QATTCHHCSKFLKGIILQGYLCGECSIAVHKQCIEF 794
Cdd:cd20792     11 QPTFCSHCKDFIWGLGKQGYQCQVCRFVVHKRCHEY 46
SH3_PIX cd11877
Src Homology 3 domain of Pak Interactive eXchange factors; PIX proteins are Rho guanine ...
 941-992 6.88e-08

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


Pssm-ID: 212810 [Multi-domain]  Cd Length: 53  Bit Score: 50.01  E-value: 6.88e-08
                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....
gi 1946280069  941 AEFDFNPSESNQLPLRKGcQVIVLSK--EGdykGWWKGKVQDRVGFFPKDYVRE 992
Cdd:cd11877      4 AKFNFEGTNEDELSFDKG-DIITVTQvvEG---GWWEGTLNGKTGWFPSNYVKE 53
SH3_CD2AP-like_1 cd11873
First Src Homology 3 domain (SH3A) of CD2-associated protein and similar proteins; This ...
 939-992 7.25e-08

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


Pssm-ID: 212806 [Multi-domain]  Cd Length: 53  Bit Score: 49.96  E-value: 7.25e-08
                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....*.
gi 1946280069  939 AIAEFDFNPSESNQLPLRKGcQVI--VLSKEGdykGWWKGKVQDRVGFFPKDYVRE 992
Cdd:cd11873      2 VIVEFDYDAEEPDELTLKVG-DIItnVKKMEE---GWWEGTLNGKRGMFPDNFVKV 53
PH_PLEKHG1_G2_G3 cd13243
Pleckstrin homology domain-containing family G members 1, 2, and 3 pleckstrin homology (PH) ...
 521-685 7.67e-08

Pleckstrin homology domain-containing family G members 1, 2, and 3 pleckstrin homology (PH) domain; PLEKHG1 (also called ARHGEF41), PLEKHG2 (also called ARHGEF42 or CLG/common-site lymphoma/leukemia guanine nucleotide exchange factor2), and PLEKHG3 (also called ARHGEF43) have RhoGEF DH/double-homology domains in tandem with a PH domain which is involved in phospholipid binding. They function as a guanine nucleotide exchange factor (GEF) and are involved in the regulation of Rho protein signal transduction. Mutations in PLEKHG1 have been associated panic disorder (PD), an anxiety disorder characterized by panic attacks and anticipatory anxiety. PH domains have diverse functions, but in general are involved in targeting proteins to the appropriate cellular location or in the interaction with a binding partner. They share little sequence conservation, but all have a common fold, which is electrostatically polarized. Less than 10% of PH domains bind phosphoinositide phosphates (PIPs) with high affinity and specificity. PH domains are distinguished from other PIP-binding domains by their specific high-affinity binding to PIPs with two vicinal phosphate groups: PtdIns(3,4)P2, PtdIns(4,5)P2 or PtdIns(3,4,5)P3 which results in targeting some PH domain proteins to the plasma membrane. A few display strong specificity in lipid binding. Any specificity is usually determined by loop regions or insertions in the N-terminus of the domain, which are not conserved across all PH domains. PH domains are found in cellular signaling proteins such as serine/threonine kinase, tyrosine kinases, regulators of G-proteins, endocytotic GTPases, adaptors, as well as cytoskeletal associated molecules and in lipid associated enzymes.


Pssm-ID: 270063 [Multi-domain]  Cd Length: 147  Bit Score: 52.74  E-value: 7.67e-08
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1946280069  521 LERAKEAMVDVAQYINEVKRDSDTLAIMSSIQvtvvrgslhlylrtdsiSDLDMPENTELKDYGRLLKDGELKIKAHDDQ 600
Cdd:cd13243      4 VEEALDTMTQVAWHINDMKRKHEHAVRVQEIQ-----------------SLLDGWEGPELTTYGDLVLEGTFRMAGAKNE 66

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1946280069  601 kiktRYIFVFDQVIIMCKSLRGETYSYRE-----SLRLQEYKIEDvhtrrtlrtdarwSYQFYLVRKSE-RTAYTLYART 674
Cdd:cd13243     67 ----RLLFLFDKMLLITKKREDGILQYKThimcsNLMLSESIPKE-------------PLSFQVLPFDNpKLQYTLQAKN 129

                          170
                   ....*....|.
gi 1946280069  675 EDNKRKWMKAI 685
Cdd:cd13243    130 QEQKRLWTQEI 140
SH3_Tec_like cd11768
Src Homology 3 domain of Tec-like Protein Tyrosine Kinases; The Tec (Tyrosine kinase expressed ...
 938-992 7.85e-08

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: 49.96  E-value: 7.85e-08
                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....*...
gi 1946280069  938 IAIAEFDFNPSESNQLPLRKGCQVIVLSKEGDYkgWWkgKVQDR---VGFFPKDYVRE 992
Cdd:cd11768      1 IVVALYDFQPIEPGDLPLEKGEEYVVLDDSNEH--WW--RARDKngnEGYIPSNYVTE 54
SH3_Intersectin1_3 cd11991
Third Src homology 3 domain (or SH3C) of Intersectin-1; Intersectin-1 (ITSN1) is an adaptor ...
 940-991 1.11e-07

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


Pssm-ID: 212924  Cd Length: 52  Bit Score: 49.21  E-value: 1.11e-07
                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|..
gi 1946280069  940 IAEFDFNPSESNQLPLRKGCQVIVLSKEGDykgWWKGKVQDRVGFFPKDYVR 991
Cdd:cd11991      3 VAMYTYESNEQGDLTFQQGDVILVTKKDGD---WWTGTVGDKTGVFPSNYVR 51
SH3_Sdc25 cd11883
Src Homology 3 domain of Sdc25/Cdc25 guanine nucleotide exchange factors; This subfamily is ...
 938-989 1.92e-07

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


Pssm-ID: 212816  Cd Length: 55  Bit Score: 48.82  E-value: 1.92e-07
                           10        20        30        40        50
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gi 1946280069  938 IAIAEFDFNPSESNQLPLRKGCQVIVLSKegDYKGWWKGKVQDRV-----GFFPKDY 989
Cdd:cd11883      1 VVVALYDFTPKSKNQLSFKAGDIIYVLNK--DPSGWWDGVIISSSgkvkrGWFPSNY 55
C1_VAV2 cd20868
protein kinase C conserved region 1 (C1 domain) found in VAV2 protein; VAV2 is widely ...
 761-802 2.31e-07

protein kinase C conserved region 1 (C1 domain) found in VAV2 protein; VAV2 is widely expressed and functions as a guanine nucleotide exchange factor (GEF) for RhoA, RhoB and RhoG and also activates Rac1 and Cdc42. It is implicated in many cellular and physiological functions including blood pressure control, eye development, neurite outgrowth and branching, EGFR endocytosis and degradation, and cell cluster morphology, among others. It has been reported to associate with Nek3. VAV proteins contain several domains that enable their function: N-terminal calponin homology (CH), acidic, RhoGEF (also called Dbl-homologous or DH), Pleckstrin Homology (PH), C1 (zinc finger), SH2, and two SH3 domains. This model corresponds to the C1 domain. The C1 domain is a cysteine-rich zinc binding domain that does not bind DNA nor possess structural similarity to conventional zinc finger domains; it contains two separate Zn(2+)-binding sites.


Pssm-ID: 410418  Cd Length: 58  Bit Score: 48.73  E-value: 2.31e-07
                           10        20        30        40
                   ....*....|....*....|....*....|....*....|..
gi 1946280069  761 TTCHHCSKFLKGIILQGYLCGECSIAVHKQCIEFSGRCHRSG 802
Cdd:cd20868     17 TNCKACKMLLRGTFYQGYYCSKCGAGAHKECLEVIPPCKIGS 58
SH3_GRAP_N cd11948
N-terminal Src homology 3 domain of GRB2-related adaptor protein; GRAP is a GRB-2 like adaptor ...
 939-991 2.41e-07

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: 48.27  E-value: 2.41e-07
                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|...
gi 1946280069  939 AIAEFDFNPSESNQLPLRKGCQVIVLSKEGDyKGWWKGKVQDRVGFFPKDYVR 991
Cdd:cd11948      2 AVALYSFQATESDELPFQKGDILKILNMEDD-QNWYKAELQGREGYIPKNYIK 53
C1 smart00109
Protein kinase C conserved region 1 (C1) domains (Cysteine-rich domains); Some bind phorbol ...
 752-794 2.57e-07

Protein kinase C conserved region 1 (C1) domains (Cysteine-rich domains); Some bind phorbol esters and diacylglycerol. Some bind RasGTP. Zinc-binding domains.


Pssm-ID: 197519  Cd Length: 50  Bit Score: 48.23  E-value: 2.57e-07
                            10        20        30        40
                    ....*....|....*....|....*....|....*....|...
gi 1946280069   752 YTPGMYLQATTCHHCSKFLKGIILQGYLCGECSIAVHKQCIEF 794
Cdd:smart00109    3 HVFRTFTKPTFCCVCRKSIWGSFKQGLRCSECKVKCHKKCADK 45
C1_cPKC_rpt1 cd20833
first protein kinase C conserved region 1 (C1 domain) found in the classical (or conventional) ...
 752-794 2.78e-07

first protein kinase C conserved region 1 (C1 domain) found in the classical (or conventional) protein kinase C (cPKC) family; PKCs are classified into three groups (classical, atypical, and novel) depending on their mode of activation and the structural characteristics of their regulatory domains. cPKCs are potent kinases for histones, myelin basic protein, and protamine. They depend on calcium, DAG (1,2-diacylglycerol), and in most cases, phosphatidylserine (PS) for activation. There are four cPKC isoforms, named alpha, betaI, betaII, and gamma. PKC-alpha is expressed in many tissues and is associated with cell proliferation, apoptosis, and cell motility. It plays a role in the signaling of the growth factors PDGF, VEGF, EGF, and FGF. Abnormal levels of PKC-alpha have been detected in many transformed cell lines and several human tumors. In addition, PKC-alpha is required for HER2 dependent breast cancer invasion. The PKC beta isoforms (I and II), generated by alternative splicing of a single gene, are preferentially activated by hyperglycemia-induced DAG (1,2-diacylglycerol) in retinal tissues. This is implicated in diabetic microangiopathy such as ischemia, neovascularization, and abnormal vasodilator function. PKC-beta also plays an important role in VEGF signaling. In addition, glucose regulates proliferation in retinal endothelial cells via PKC-betaI. PKC-beta is also being explored as a therapeutic target in cancer. It contributes to tumor formation and is involved in the tumor host mechanisms of inflammation and angiogenesis. PKC-gamma is mainly expressed in neuronal tissues. It plays a role in protection from ischemia. Members of this family contain two copies of the C1 domain. This model corresponds to the first one. The C1 domain is a cysteine-rich zinc binding domain that does not bind DNA nor possess structural similarity to conventional zinc finger domains; it contains two separate Zn(2+)-binding sites.


Pssm-ID: 410383  Cd Length: 58  Bit Score: 48.56  E-value: 2.78e-07
                           10        20        30        40
                   ....*....|....*....|....*....|....*....|...
gi 1946280069  752 YTPGMYLQATTCHHCSKFLKGIILQGYLCGECSIAVHKQCIEF 794
Cdd:cd20833      5 FIARFFKQPTFCSHCTDFIWGFGKQGFQCQVCSFVVHKRCHEF 47
SH3_Nck2_2 cd11902
Second Src Homology 3 domain of Nck2 adaptor protein; Nck2 (also called Nckbeta or Growth ...
 937-992 2.91e-07

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


Pssm-ID: 212835 [Multi-domain]  Cd Length: 55  Bit Score: 48.08  E-value: 2.91e-07
                           10        20        30        40        50
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gi 1946280069  937 IIAIAEFDFNPSESNQLPLRKGCQVIVLSKEGDykGWWKGKVQDRVGFFPKDYVRE 992
Cdd:cd11902      1 IPAFVKFAYVAEREDELSLVKGSRVTVMEKCSD--GWWRGSYNGQIGWFPSNYVVE 54
SH3_Intersectin_3 cd11838
Third Src homology 3 domain (or SH3C) of Intersectin; Intersectins (ITSNs) are adaptor ...
 940-992 2.94e-07

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


Pssm-ID: 212772 [Multi-domain]  Cd Length: 52  Bit Score: 48.18  E-value: 2.94e-07
                           10        20        30        40        50
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gi 1946280069  940 IAEFDFNPSESNQLPLRKGCQVIVLSKEGDykgWWKGKVQDRVGFFPKDYVRE 992
Cdd:cd11838      3 IALYPYESNEPGDLTFNAGDVILVTKKDGE---WWTGTIGDRTGIFPSNYVRP 52
C1 cd00029
protein kinase C conserved region 1 (C1 domain) superfamily; The C1 domain is a cysteine-rich ...
 754-794 3.05e-07

protein kinase C conserved region 1 (C1 domain) superfamily; The C1 domain is a cysteine-rich zinc binding domain that does not bind DNA nor possess structural similarity to conventional zinc finger domains. It contains the motif HX12CX2CXnCX2CX4HX2CX7C, where C and H are cysteine and histidine, respectively; X represents other residues; and n is either 13 or 14. C1 has a globular fold with two separate Zn(2+)-binding sites. It was originally discovered as lipid-binding modules in protein kinase C (PKC) isoforms. C1 domains that bind and respond to phorbol esters (PE) and diacylglycerol (DAG) are referred to as typical, and those that do not respond to PE and DAG are deemed atypical. A C1 domain may also be referred to as PKC or non-PKC C1, based on the parent protein's activity. Most C1 domain-containing non-PKC proteins act as lipid kinases and scaffolds, except PKD which acts as a protein kinase. PKC C1 domains play roles in membrane translocation and activation of the enzyme.


Pssm-ID: 410341  Cd Length: 50  Bit Score: 47.90  E-value: 3.05e-07
                           10        20        30        40
                   ....*....|....*....|....*....|....*....|.
gi 1946280069  754 PGMYLQATTCHHCSKFLKGIILQGYLCGECSIAVHKQCIEF 794
Cdd:cd00029      5 PTTFSSPTFCDVCGKLIWGLFKQGLKCSDCGLVCHKKCLDK 45
SH3_GRB2_like_N cd11804
N-terminal Src homology 3 domain of Growth factor receptor-bound protein 2 (GRB2) and related ...
 939-990 3.62e-07

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: 47.74  E-value: 3.62e-07
                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|..
gi 1946280069  939 AIAEFDFNPSESNQLPLRKGCQVIVLSKEGDyKGWWKGKVQDRVGFFPKDYV 990
Cdd:cd11804      2 AVAKHDFKATAEDELSFKKGSILKVLNMEDD-PNWYKAELDGKEGLIPKNYI 52
C1_PKD_rpt2 cd20796
second protein kinase C conserved region 1 (C1 domain) found in the family of protein kinase D ...
 757-794 4.63e-07

second protein kinase C conserved region 1 (C1 domain) found in the family of protein kinase D (PKD); PKDs are important regulators of many intracellular signaling pathways such as ERK and JNK, and cellular processes including the organization of the trans-Golgi network, membrane trafficking, cell proliferation, migration, and apoptosis. They are activated in a PKC-dependent manner by many agents including diacylglycerol (DAG), PDGF, neuropeptides, oxidative stress, and tumor-promoting phorbol esters, among others. Mammals harbor three types of PKDs: PKD1 (or PKCmu), PKD2, and PKD3 (or PKCnu). PKDs contain N-terminal tandem cysteine-rich zinc binding C1 (PKC conserved region 1), central PH (Pleckstrin Homology), and C-terminal catalytic kinase domains. This model corresponds to the second C1 domain. The C1 domain is a cysteine-rich zinc binding domain that does not bind DNA nor possess structural similarity to conventional zinc finger domains; it contains two separate Zn(2+)-binding sites.


Pssm-ID: 410346  Cd Length: 54  Bit Score: 47.67  E-value: 4.63e-07
                           10        20        30
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gi 1946280069  757 YLQATTCHHCSKFLKGIILQGYLCGECSIAVHKQCIEF 794
Cdd:cd20796      9 YTKPTVCQHCKKLLKGLFRQGLQCKDCKFNCHKKCAEK 46
SH3_Blk cd12009
Src homology 3 domain of Blk Protein Tyrosine Kinase; Blk is a member of the Src subfamily of ...
 940-990 6.00e-07

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: 47.50  E-value: 6.00e-07
                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|...
gi 1946280069  940 IAEFDFNPSESNQLPLRKGCQVIVLSKEGDykgWWKGK--VQDRVGFFPKDYV 990
Cdd:cd12009      3 IAQYDFVPSNERDLQLKKGEKLQVLKSDGE---WWLAKslTTGKEGYIPSNYV 52
C1_1 pfam00130
Phorbol esters/diacylglycerol binding domain (C1 domain); This domain is also known as the ...
 757-794 6.00e-07

Phorbol esters/diacylglycerol binding domain (C1 domain); This domain is also known as the Protein kinase C conserved region 1 (C1) domain.


Pssm-ID: 395079  Cd Length: 53  Bit Score: 47.44  E-value: 6.00e-07
                           10        20        30
                   ....*....|....*....|....*....|....*...
gi 1946280069  757 YLQATTCHHCSKFLKGIILQGYLCGECSIAVHKQCIEF 794
Cdd:pfam00130    8 FKQPTFCDHCGEFLWGLGKQGLKCSWCKLNVHKRCHEK 45
C1_nPKC_theta-like_rpt1 cd20834
first protein kinase C conserved region 1 (C1 domain) found in novel protein kinase C (nPKC) ...
 759-802 7.05e-07

first protein kinase C conserved region 1 (C1 domain) found in novel protein kinase C (nPKC) theta, delta, and similar proteins; PKCs are classified into three groups (classical, atypical, and novel) depending on their mode of activation and the structural characteristics of their regulatory domains. nPKCs are calcium-independent, but require DAG (1,2-diacylglycerol) and phosphatidylserine (PS) for activity. PKC-theta is selectively expressed in T-cells and plays an important and non-redundant role in several aspects of T-cell biology. PKC-delta plays a role in cell cycle regulation and programmed cell death in many cell types. Members of this family contain two copies of the C1 domain. This model corresponds to the first one. The C1 domain is a cysteine-rich zinc binding domain that does not bind DNA nor possess structural similarity to conventional zinc finger domains; it contains two separate Zn(2+)-binding sites.


Pssm-ID: 410384  Cd Length: 61  Bit Score: 47.32  E-value: 7.05e-07
                           10        20        30        40
                   ....*....|....*....|....*....|....*....|....*
gi 1946280069  759 QATTCHHCSKFLKGIILQGYLCGECSIAVHKQCIE-FSGRCHRSG 802
Cdd:cd20834     17 QPTFCSVCKEFLWGFNKQGYQCRQCNAAVHKKCHDkILGKCPGSA 61
SH3_alphaPIX cd12060
Src Homology 3 domain of alpha-Pak Interactive eXchange factor; Alpha-PIX, also called Rho ...
 936-992 7.92e-07

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


Pssm-ID: 212993  Cd Length: 58  Bit Score: 47.30  E-value: 7.92e-07
                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....*..
gi 1946280069  936 RIIAIAEFDFNPSESNQLPLRKGcQVIVLSKEGDyKGWWKGKVQDRVGFFPKDYVRE 992
Cdd:cd12060      1 QLVVKARFNFKQTNEDELSVCKG-DIIYVTRVEE-GGWWEGTLNGKTGWFPSNYVRE 55
SH3_betaPIX cd12061
Src Homology 3 domain of beta-Pak Interactive eXchange factor; Beta-PIX, also called Rho ...
 941-992 8.37e-07

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


Pssm-ID: 212994 [Multi-domain]  Cd Length: 54  Bit Score: 46.99  E-value: 8.37e-07
                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|..
gi 1946280069  941 AEFDFNPSESNQLPLRKGcQVIVLSKEGDyKGWWKGKVQDRVGFFPKDYVRE 992
Cdd:cd12061      4 AKFNFQQTNEDELSFSKG-DVIHVTRVEE-GGWWEGTHNGRTGWFPSNYVRE 53
SH3_Intersectin1_5 cd11995
Fifth Src homology 3 domain (or SH3E) of Intersectin-1; Intersectin-1 (ITSN1) is an adaptor ...
 940-991 1.19e-06

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


Pssm-ID: 212928 [Multi-domain]  Cd Length: 54  Bit Score: 46.49  E-value: 1.19e-06
                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|..
gi 1946280069  940 IAEFDFNPSESNQLPLRKGCQVIVLSKEGdyKGWWKGKVQDRVGFFPKDYVR 991
Cdd:cd11995      4 IGMYDYTAQNDDELAFSKGQIINVLNKED--PDWWKGELNGQVGLFPSNYVK 53
C1_CeDKF1-like_rpt2 cd20798
second protein kinase C conserved region 1 (C1 domain) found in Caenorhabditis elegans serine ...
 757-791 1.20e-06

second protein kinase C conserved region 1 (C1 domain) found in Caenorhabditis elegans serine/threonine-protein kinase DKF-1 and similar proteins; DKF-1 converts transient diacylglycerol (DAG) signals into prolonged physiological effects, independently of PKC. It plays a role in the regulation of growth and neuromuscular control of movement. It is involved in immune response to Staphylococcus aureus bacterium by activating transcription factor hlh-30 downstream of phospholipase plc-1. Members of this group contain two copies of the C1 domain. This model corresponds to the second one. The C1 domain is a cysteine-rich zinc binding domain that does not bind DNA nor possess structural similarity to conventional zinc finger domains; it contains two separate Zn(2+)-binding sites.


Pssm-ID: 410348  Cd Length: 54  Bit Score: 46.34  E-value: 1.20e-06
                           10        20        30
                   ....*....|....*....|....*....|....*
gi 1946280069  757 YLQATTCHHCSKFLKGIILQGYLCGECSIAVHKQC 791
Cdd:cd20798      9 YKKPTVCKVCDKLLVGLVRQGLKCRDCGVNVHKKC 43
SH3_9 pfam14604
Variant SH3 domain;
941-991 1.22e-06

Variant SH3 domain;


Pssm-ID: 434066 [Multi-domain]  Cd Length: 49  Bit Score: 46.07  E-value: 1.22e-06
                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|.
gi 1946280069  941 AEFDFNPSESNQLPLRKGCQVIVLSKEGDykGWWKGKVQDRVGFFPKDYVR 991
Cdd:pfam14604    1 ALYPYEPKDDDELSLQRGDVITVIEESED--GWWEGINTGRTGLVPANYVE 49
SH3_Intersectin_5 cd11840
Fifth Src homology 3 domain (or SH3E) of Intersectin; Intersectins (ITSNs) are adaptor ...
 940-992 1.25e-06

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: 46.25  E-value: 1.25e-06
                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|...
gi 1946280069  940 IAEFDFNPSESNQLPLRKGCQVIVLSKegDYKGWWKGKVQDRVGFFPKDYVRE 992
Cdd:cd11840      3 IALFPYTAQNEDELSFQKGDIINVLSK--DDPDWWRGELNGQTGLFPSNYVEP 53
SH3_GRB2_C cd11949
C-terminal Src homology 3 domain of Growth factor receptor-bound protein 2; GRB2 is a critical ...
 941-991 1.48e-06

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


Pssm-ID: 212882 [Multi-domain]  Cd Length: 53  Bit Score: 46.37  E-value: 1.48e-06
                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|.
gi 1946280069  941 AEFDFNPSESNQLPLRKGcQVIVLSKEGDyKGWWKGKVQDRVGFFPKDYVR 991
Cdd:cd11949      4 ALFDFDPQEDGELGFRRG-DFIEVMDNSD-PNWWKGACHGQTGMFPRNYVT 52
C1_DGKtheta_typeV_rpt1 cd20803
first protein kinase C conserved region 1 (C1 domain) found in type V diacylglycerol kinase, ...
 761-796 1.53e-06

first protein kinase C conserved region 1 (C1 domain) found in type V diacylglycerol kinase, DAG kinase theta, and similar proteins; Diacylglycerol (DAG) kinase (EC 2.7.1.107) is a lipid kinase that phosphorylates diacylglycerol to form phosphatidic acid. DAG kinase theta, also called diglyceride kinase theta (DGK-theta), is the only isoform classified as type V; it contains a pleckstrin homology (PH)-like domain and an additional C1 domain, compared to other DGKs. It may regulate the activity of protein kinase C by controlling the balance between the two signaling lipids, diacylglycerol and phosphatidic acid. DAG kinase theta contains three copies of the C1 domain. This model corresponds to the first one. The C1 domain is a cysteine-rich zinc binding domain that does not bind DNA nor possess structural similarity to conventional zinc finger domains; it contains two separate Zn(2+)-binding sites.


Pssm-ID: 410353  Cd Length: 56  Bit Score: 46.15  E-value: 1.53e-06
                           10        20        30
                   ....*....|....*....|....*....|....*.
gi 1946280069  761 TTCHHCSKFLKGIILQGYLCGECSIAVHKQCIEFSG 796
Cdd:cd20803     13 TYCHHCTDLLWGLLNQGYQCEVCNFVSHERCLKTVV 48
C1_RASGRP4 cd20863
protein kinase C conserved region 1 (C1 domain) found in RAS guanyl-releasing protein 4 ...
 757-793 1.55e-06

protein kinase C conserved region 1 (C1 domain) found in RAS guanyl-releasing protein 4 (RASGRP4) and similar proteins; RASGRP4 functions as a cation- and diacylglycerol (DAG)-regulated nucleotide exchange factor activating Ras through the exchange of bound GDP for GTP. It may function in mast cell differentiation. The C1 domain is a cysteine-rich zinc binding domain that does not bind DNA nor possess structural similarity to conventional zinc finger domains; it contains two separate Zn(2+)-binding sites.


Pssm-ID: 410413  Cd Length: 57  Bit Score: 46.31  E-value: 1.55e-06
                           10        20        30
                   ....*....|....*....|....*....|....*..
gi 1946280069  757 YLQATTCHHCSKFLKGIILQGYLCGECSIAVHKQCIE 793
Cdd:cd20863     11 FKKPTFCDSCSGFLWGVTKQGYRCQDCGINCHKHCKD 47
C1_VAV3 cd20869
protein kinase C conserved region 1 (C1 domain) found in VAV3 protein; VAV3 is ubiquitously ...
 759-800 1.79e-06

protein kinase C conserved region 1 (C1 domain) found in VAV3 protein; VAV3 is ubiquitously expressed and functions as a phosphorylation-dependent guanine nucleotide exchange factor (GEF) for RhoA, RhoG, and Rac1. Its function has been implicated 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 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. This model corresponds to the C1 domain. The C1 domain is a cysteine-rich zinc binding domain that does not bind DNA nor possess structural similarity to conventional zinc finger domains; it contains two separate Zn(2+)-binding sites.


Pssm-ID: 410419  Cd Length: 59  Bit Score: 45.97  E-value: 1.79e-06
                           10        20        30        40
                   ....*....|....*....|....*....|....*....|..
gi 1946280069  759 QATTCHHCSKFLKGIILQGYLCGECSIAVHKQCIEFSGRCHR 800
Cdd:cd20869     18 RVTSCKVCQMLLRGTFYQGYLCSKCGAGAHKECLGRLDSCGR 59
C1_RASGRP3 cd20862
protein kinase C conserved region 1 (C1 domain) found in RAS guanyl-releasing protein 3 ...
 757-791 1.87e-06

protein kinase C conserved region 1 (C1 domain) found in RAS guanyl-releasing protein 3 (RASGRP3) and similar proteins; RASGRP3, also called calcium and DAG-regulated guanine nucleotide exchange factor III (CalDAG-GEFIII), or guanine nucleotide exchange factor for Rap1, is a guanine nucleotide-exchange factor activating H-Ras, R-Ras and Ras-associated protein-1/2. It functions as an important mediator of signaling downstream from receptor coupled phosphoinositide turnover in B and T cells. The C1 domain is a cysteine-rich zinc binding domain that does not bind DNA nor possess structural similarity to conventional zinc finger domains; it contains two separate Zn(2+)-binding sites.


Pssm-ID: 410412  Cd Length: 59  Bit Score: 46.18  E-value: 1.87e-06
                           10        20        30
                   ....*....|....*....|....*....|....*
gi 1946280069  757 YLQATTCHHCSKFLKGIILQGYLCGECSIAVHKQC 791
Cdd:cd20862     15 YLKPTFCEHCAGFLWGIIKQGYKCKDCGVNCHKQC 49
SH3_Intersectin_4 cd11839
Fourth Src homology 3 domain (or SH3D) of Intersectin; Intersectins (ITSNs) are adaptor ...
 944-991 1.88e-06

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


Pssm-ID: 212773 [Multi-domain]  Cd Length: 58  Bit Score: 46.18  E-value: 1.88e-06
                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|...
gi 1946280069  944 DFNPSESNQLPLRKGCQVIVLSKEGDykGWWKGKVQDR-----VGFFPKDYVR 991
Cdd:cd11839      7 PFTATAENQLSLAVGQLVLVRKKSPS--GWWEGELQARgkkrqIGWFPANYVK 57
SH3_BTK cd11906
Src Homology 3 domain of Bruton's tyrosine kinase; BTK is a cytoplasmic (or nonreceptor) tyr ...
 940-992 1.91e-06

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: 45.97  E-value: 1.91e-06
                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....
gi 1946280069  940 IAEFDFNPSESNQLPLRKGCQVIVLsKEGDYKgWWKGK-VQDRVGFFPKDYVRE 992
Cdd:cd11906      4 VALYDYTPMNAQDLQLRKGEEYVIL-EESNLP-WWRARdKNGREGYIPSNYVTE 55
SH3_SNX9_like cd11763
Src Homology 3 domain of Sorting Nexin 9 and similar proteins; Sorting nexins (SNXs) are Phox ...
 941-990 2.36e-06

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: 45.78  E-value: 2.36e-06
                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|.
gi 1946280069  941 AEFDFNPSESNQLPLRKGcQVIVLSKEGDYKGWWKGK-VQDRVGFFPKDYV 990
Cdd:cd11763      4 ALYDFDSQPSGELSLRAG-EVLTITRQDVGDGWLEGRnSRGEVGLFPSSYV 53
SH3_Intersectin_2 cd11837
Second Src homology 3 domain (or SH3B) of Intersectin; Intersectins (ITSNs) are adaptor ...
 939-992 2.65e-06

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: 45.43  E-value: 2.65e-06
                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....*
gi 1946280069  939 AIAEFDFNPSESNQLPLRKGCQVIVLSKEGDykgWWKGKVQD-RVGFFPKDYVRE 992
Cdd:cd11837      2 ATALYPWRAKKENHLSFAKGDIITVLEQQEM---WWFGELEGgEEGWFPKSYVKE 53
SH3_Nostrin cd11823
Src homology 3 domain of Nitric Oxide Synthase TRaffic INducer; Nostrin is expressed in ...
 941-992 2.75e-06

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


Pssm-ID: 212757 [Multi-domain]  Cd Length: 53  Bit Score: 45.41  E-value: 2.75e-06
                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|..
gi 1946280069  941 AEFDFNPSESNQLPLRKGCQVIVLSKEGDykGWWKGKVQDRVGFFPKDYVRE 992
Cdd:cd11823      4 ALYSYTANREDELSLQPGDIIEVHEKQDD--GWWLGELNGKKGIFPATYVEE 53
SH3_Sorbs_1 cd11781
First Src Homology 3 domain of Sorbin and SH3 domain containing (Sorbs) proteins and similar ...
 939-990 2.84e-06

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


Pssm-ID: 212715 [Multi-domain]  Cd Length: 53  Bit Score: 45.41  E-value: 2.84e-06
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gi 1946280069  939 AIAEFDFNPSESNQLPLRKGcQVIVLSKEGDyKGWWKGKVQDRVGFFPKDYV 990
Cdd:cd11781      2 ARALYPFKAQSAKELSLKKG-DIIYIRRQID-KNWYEGEHNGRVGIFPASYV 51
SH3_p67phox_C cd12046
C-terminal (or second) Src Homology 3 domain of the p67phox subunit of NADPH oxidase; p67phox, ...
 940-992 3.56e-06

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


Pssm-ID: 212979 [Multi-domain]  Cd Length: 53  Bit Score: 45.18  E-value: 3.56e-06
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gi 1946280069  940 IAEFDFNPSESNQLPLRKGCQVIVLSKEGDykGWWKGKVQDRVGFFPKDYVRE 992
Cdd:cd12046      3 VALFSYEASQPEDLEFQKGDVILVLSKVNE--DWLEGQCKGKIGIFPSAFVED 53
C1_RASGRP1 cd20860
protein kinase C conserved region 1 (C1 domain) found in RAS guanyl-releasing protein 1 ...
 757-791 3.88e-06

protein kinase C conserved region 1 (C1 domain) found in RAS guanyl-releasing protein 1 (RASGRP1) and similar proteins; RASGRP1, also called calcium and DAG-regulated guanine nucleotide exchange factor II (CalDAG-GEFII) or Ras guanyl-releasing protein, functions as a calcium- and diacylglycerol (DAG)-regulated nucleotide exchange factor specifically activating Ras through the exchange of bound GDP for GTP. It activates the Erk/MAP kinase cascade and regulates T-cell/B-cell development, homeostasis and differentiation by coupling T-lymphocyte/B-lymphocyte antigen receptors to Ras. RASGRP1 also regulates NK cell cytotoxicity and ITAM-dependent cytokine production by activation of Ras-mediated ERK and JNK pathways. The C1 domain is a cysteine-rich zinc binding domain that does not bind DNA nor possess structural similarity to conventional zinc finger domains; it contains two separate Zn(2+)-binding sites.


Pssm-ID: 410410  Cd Length: 55  Bit Score: 44.92  E-value: 3.88e-06
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gi 1946280069  757 YLQATTCHHCSKFLKGIILQGYLCGECSIAVHKQC 791
Cdd:cd20860     10 YLKPTFCDNCAGFLWGVIKQGYRCKDCGMNCHKQC 44
SH3_Myosin-I_fungi cd11858
Src homology 3 domain of Type I fungal Myosins; Type I myosins (myosin-I) are actin-dependent ...
 941-992 4.04e-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: 45.07  E-value: 4.04e-06
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gi 1946280069  941 AEFDFNPSESNQLPLRKGCQVIVLSKEGDykGWWKGKVQDRV--GFFPKDYVRE 992
Cdd:cd11858      4 ALYDFAGSVANELSLKKDDIVYIVQKEDN--GWWLAKKLDESkeGWVPAAYLEE 55
C1_cPKC_nPKC_rpt2 cd20793
second protein kinase C conserved region 1 (C1 domain) found in classical (or conventional) ...
 751-793 5.20e-06

second protein kinase C conserved region 1 (C1 domain) found in classical (or conventional) protein kinase C (cPKC), novel protein kinase C (nPKC), and similar proteins; PKCs are classified into three groups (classical, atypical, and novel) depending on their mode of activation and the structural characteristics of their regulatory domain. PKCs undergo three phosphorylations in order to take mature forms. In addition, cPKCs depend on calcium, DAG (1,2-diacylglycerol), and in most cases, phosphatidylserine (PS) for activation. nPKCs are calcium-independent, but require DAG and PS for activity, while atypical PKCs (aPKCs) only require PS. PKCs phosphorylate and modify the activities of a wide variety of cellular proteins including receptors, enzymes, cytoskeletal proteins, transcription factors, and other kinases. They play a central role in signal transduction pathways that regulate cell migration and polarity, proliferation, differentiation, and apoptosis. This family includes classical PKCs (cPKCs) and novel PKCs (nPKCs). There are four cPKC isoforms (named alpha, betaI, betaII, and gamma) and four nPKC isoforms (delta, epsilon, eta, and theta). Members of this family contain two copies of C1 domain. This model corresponds to the second one. The C1 domain is a cysteine-rich zinc binding domain that does not bind DNA nor possess structural similarity to conventional zinc finger domains; it contains two separate Zn(2+)-binding sites.


Pssm-ID: 410343  Cd Length: 50  Bit Score: 44.58  E-value: 5.20e-06
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gi 1946280069  751 YYTPgmylqaTTCHHCSKFLKGIILQGYLCGECSIAVHKQCIE 793
Cdd:cd20793      8 YYSP------TFCDHCGSLLYGLVRQGLKCKDCGMNVHHRCKE 44
SH3_GRB2_N cd11946
N-terminal Src homology 3 domain of Growth factor receptor-bound protein 2; GRB2 is a critical ...
 939-991 5.42e-06

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: 44.63  E-value: 5.42e-06
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gi 1946280069  939 AIAEFDFNPSESNQLPLRKGCQVIVLSKEGDyKGWWKGKVQDRVGFFPKDYVR 991
Cdd:cd11946      3 AIAKYDFKATADDELSFKRGDILKVLNEECD-QNWYKAELNGKDGFIPKNYIE 54
SH3_PACSIN cd11843
Src homology 3 domain of Protein kinase C and Casein kinase Substrate in Neurons (PACSIN) ...
 941-990 7.59e-06

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


Pssm-ID: 212777 [Multi-domain]  Cd Length: 53  Bit Score: 44.33  E-value: 7.59e-06
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gi 1946280069  941 AEFDFNPSESNQLPLRKGCQVIVLSKEgDYKGWWKGKVQDRVGFFPKDYV 990
Cdd:cd11843      4 ALYDYEGQESDELSFKAGDILTKLEEE-DEQGWCKGRLDGRVGLYPANYV 52
C1_CHN cd20806
protein kinase C conserved region 1 (C1 domain) found in the chimaerin family; Chimaerins are ...
 757-793 9.59e-06

protein kinase C conserved region 1 (C1 domain) found in the chimaerin family; Chimaerins are a family of phorbolester- and diacylglycerol-responsive GTPase activating proteins (GAPs) specific for the Rho-like GTPase Rac. Alpha1-chimerin (formerly known as N-chimerin) and alpha2-chimerin are alternatively spliced products of a single gene, as are beta1- and beta2-chimerin. Alpha1- and beta1-chimerin have a relatively short N-terminal region that does not encode any recognizable domains, whereas alpha2- and beta2-chimerin both include a functional SH2 domain that can bind to phosphotyrosine motifs within receptors. All the isoforms contain a GAP domain with specificity in vitro for Rac1 and a diacylglycerol (DAG)-binding C1 domain which allows them to translocate to membranes in response to DAG signaling and anchors them in close proximity to activated Rac. This model corresponds to the C1 domain. The C1 domain is a cysteine-rich zinc binding domain that does not bind DNA nor possess structural similarity to conventional zinc finger domains; it contains two separate Zn(2+)-binding sites.


Pssm-ID: 410356  Cd Length: 53  Bit Score: 43.84  E-value: 9.59e-06
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gi 1946280069  757 YLQATTCHHCSKFLKGIILQGYLCGECSIAVHKQCIE 793
Cdd:cd20806      9 FKGPHWCDYCGNFMWGLIAQGVKCEDCGFNAHKQCSK 45
SH2_C-SH2_SHP_like cd09931
C-terminal Src homology 2 (C-SH2) domain found in SH2 domain Phosphatases (SHP) proteins; The ...
 831-934 1.01e-05

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


Pssm-ID: 198185  Cd Length: 99  Bit Score: 45.35  E-value: 1.01e-05
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gi 1946280069  831 WFVGEM-GRDRASALLERHMDGTYLLRvrpQGATHPNEtiYALSLKTDD-RVKHMKVYertMEGVPHYFLSESRfFRSIT 908
Cdd:cd09931      2 WFHGHLsGKEAEKLLLEKGKPGSFLVR---ESQSKPGD--FVLSVRTDDdKVTHIMIR---CQGGKYDVGGGEE-FDSLT 72

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gi 1946280069  909 DLIGCYEHSSLgENFVGLDVTLKWPF 934
Cdd:cd09931     73 DLVEHYKKNPM-VETSGTVVHLKQPL 97
SH3_PSTPIP1 cd11824
Src homology 3 domain of Proline-Serine-Threonine Phosphatase-Interacting Protein 1; PSTPIP1, ...
 939-990 1.13e-05

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


Pssm-ID: 212758 [Multi-domain]  Cd Length: 53  Bit Score: 43.52  E-value: 1.13e-05
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gi 1946280069  939 AIAEFDFNPSESNQLPLRKGCQVIVLSKEGDykGWWKGKVQDRVGFFPKDYV 990
Cdd:cd11824      2 YSVLYDYTAQEDDELSISKGDVVAVIEKGED--GWWTVERNGQKGLVPGTYL 51
SH2_Tec_family cd09934
Src homology 2 (SH2) domain found in Tec-like proteins; The Tec protein tyrosine kinase is the ...
 825-920 1.29e-05

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


Pssm-ID: 198188  Cd Length: 104  Bit Score: 45.08  E-value: 1.29e-05
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gi 1946280069  825 SLKDHLWFVGEMGRDRASALL-ERHMDGTYLLRVRPQGAThpnetiYALSLKT----DDRVKHMKVyERTMEGvpHYFLS 899
Cdd:cd09934      2 NLEKYEWYVGDMSRQRAESLLkQEDKEGCFVVRNSSTKGL------YTVSLFTkvpgSPHVKHYHI-KQNARS--EFYLA 72

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gi 1946280069  900 ESRFFRSITDLIGCYEHSSLG 920
Cdd:cd09934     73 EKHCFETIPELINYHQHNSGG 93
SH3_SKAP1 cd12044
Src Homology 3 domain of Src Kinase-Associated Phosphoprotein 1; SKAP1, also called SKAP55 ...
 943-990 1.43e-05

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


Pssm-ID: 212977  Cd Length: 53  Bit Score: 43.31  E-value: 1.43e-05
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gi 1946280069  943 FDFNPSESNQLPLRKGCQVIVLSKEGDYKGWWKGKVQDRVGFFPKDYV 990
Cdd:cd12044      6 WDCFGDNPDELSFQRGDLIYILSKEYNMYGWWVGELNGIVGIVPKDYL 53
SH3_CD2AP-like_2 cd11874
Second Src Homology 3 domain (SH3B) of CD2-associated protein and similar proteins; This ...
 941-992 1.57e-05

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


Pssm-ID: 212807 [Multi-domain]  Cd Length: 53  Bit Score: 43.09  E-value: 1.57e-05
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gi 1946280069  941 AEFDFNPSESNQLPLRKGCQVIVLSKEGDykGWWKGKVQDRVGFFPKDYVRE 992
Cdd:cd11874      4 VLFSYTPQNEDELELKVGDTIEVLGEVEE--GWWEGKLNGKVGVFPSNFVKE 53
SH2_a2chimerin_b2chimerin cd10352
Src homology 2 (SH2) domain found in alpha2-chimerin and beta2-chimerin proteins; Chimerins ...
 832-911 1.86e-05

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


Pssm-ID: 198215  Cd Length: 91  Bit Score: 44.28  E-value: 1.86e-05
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gi 1946280069  832 FVGEMGRDRASALLERHMDGTYLLRVRPQgathpNETIYALSLKTDDRVKHMKVYertMEGVPHYFLSESRFFRSITDLI 911
Cdd:cd10352      9 YHGLISREEAEQLLSGASDGSYLIRESSR-----DDGYYTLSLRFNGKVKNYKLY---YDGKNHYHYVGEKRFDTIHDLV 80
C1_PKD1_rpt2 cd20842
second protein kinase C conserved region 1 (C1 domain) found in protein kinase D (PKD) and ...
 757-791 1.94e-05

second protein kinase C conserved region 1 (C1 domain) found in protein kinase D (PKD) and similar proteins; PKD is also called PKD1, PRKD1, protein kinase C mu type (nPKC-mu), PRKCM, serine/threonine-protein kinase D1, or nPKC-D1. It is a serine/threonine-protein kinase that converts transient diacylglycerol (DAG) signals into prolonged physiological effects downstream of PKC, and is involved in the regulation of MAPK8/JNK1 and Ras signaling, Golgi membrane integrity and trafficking, cell survival through NF-kappa-B activation, cell migration, cell differentiation by mediating HDAC7 nuclear export, cell proliferation via MAPK1/3 (ERK1/2) signaling, and plays a role in cardiac hypertrophy, VEGFA-induced angiogenesis, genotoxic-induced apoptosis and flagellin-stimulated inflammatory response. PKD contains N-terminal tandem cysteine-rich zinc binding C1 (PKC conserved region 1), central PH (Pleckstrin Homology), and C-terminal catalytic kinase domains. This model corresponds to the second C1 domain. The C1 domain is a cysteine-rich zinc binding domain that does not bind DNA nor possess structural similarity to conventional zinc finger domains; it contains two separate Zn(2+)-binding sites.


Pssm-ID: 410392  Cd Length: 94  Bit Score: 44.23  E-value: 1.94e-05
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gi 1946280069  757 YLQATTCHHCSKFLKGIILQGYLCGECSIAVHKQC 791
Cdd:cd20842     42 YTRPTVCQYCKKLLKGLFRQGLQCKDCKFNCHKRC 76
SH3_Sorbs1_1 cd11919
First Src Homology 3 domain of Sorbin and SH3 domain containing 1 (Sorbs1), also called ponsin; ...
 939-990 2.00e-05

First Src Homology 3 domain of Sorbin and SH3 domain containing 1 (Sorbs1), also called ponsin; Sorbs1 is also called ponsin, SH3P12, or CAP (c-Cbl associated protein). It is an adaptor protein containing one sorbin homology (SoHo) and three SH3 domains. It binds Cbl and plays a major role in regulating the insulin signaling pathway by enhancing insulin-induced phosphorylation of Cbl. Sorbs1, like vinexin, localizes at cell-ECM and cell-cell adhesion sites where it binds vinculin, paxillin, and afadin. It may function in the control of cell motility. Other interaction partners of Sorbs1 include c-Abl, Sos, flotillin, Grb4, ataxin-7, filamin C, among others. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 212852 [Multi-domain]  Cd Length: 55  Bit Score: 43.03  E-value: 2.00e-05
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gi 1946280069  939 AIAEFDFNPSESNQLPLRKGcQVIVLSKEGDyKGWWKGKVQDRVGFFPKDYV 990
Cdd:cd11919      3 ARAKFDFKAQTLKELPLQKG-DIVYIYKQID-QNWYEGEHHGRVGIFPRSYI 52
SH3_STAM1 cd11964
Src homology 3 domain of Signal Transducing Adaptor Molecule 1; STAM1 is part of the endosomal ...
 935-990 2.00e-05

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


Pssm-ID: 212897 [Multi-domain]  Cd Length: 55  Bit Score: 43.01  E-value: 2.00e-05
                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....*.
gi 1946280069  935 RRIIAIaeFDFNPSESNQLPLRKGcQVIVLSKEGDyKGWWKGKVQDRVGFFPKDYV 990
Cdd:cd11964      1 RKVRAI--YDFEAAEDNELTFKAG-DIITILDDSD-PNWWKGETPQGTGLFPSNFV 52
C1_nPKC_epsilon-like_rpt1 cd20835
first protein kinase C conserved region 1 (C1 domain) found in novel protein kinase C (nPKC) ...
 759-791 2.12e-05

first protein kinase C conserved region 1 (C1 domain) found in novel protein kinase C (nPKC) epsilon, eta, and similar proteins; PKCs are classified into three groups (classical, atypical, and novel) depending on their mode of activation and the structural characteristics of their regulatory domains. nPKCs are calcium-independent, but require DAG (1,2-diacylglycerol) and phosphatidylserine (PS) for activity. PKC-epsilon has been shown to behave as an oncoprotein. Its overexpression contributes to neoplastic transformation depending on the cell type. It contributes to oncogenesis by inducing disordered cell growth and inhibiting cell death. It also plays a role in tumor invasion and metastasis. PKC-epsilon has also been found to confer cardioprotection against ischemia and reperfusion-mediated damage. Other cellular functions include the regulation of gene expression, cell adhesion, and cell motility. PKC-eta is predominantly expressed in squamous epithelia, where it plays a crucial role in the signaling of cell-type specific differentiation. It is also expressed in pro-B cells and early-stage thymocytes, and acts as a key regulator in early B-cell development. PKC-eta increases glioblastoma multiforme (GBM) proliferation and resistance to radiation, and is being developed as a therapeutic target for the management of GBM. Members of this family contain two copies of the C1 domain. This model corresponds to the first one. The C1 domain is a cysteine-rich zinc binding domain that does not bind DNA nor possess structural similarity to conventional zinc finger domains; it contains two separate Zn(2+)-binding sites.


Pssm-ID: 410385  Cd Length: 64  Bit Score: 43.22  E-value: 2.12e-05
                           10        20        30
                   ....*....|....*....|....*....|....
gi 1946280069  759 QATTCHHCSKFLKGIIL-QGYLCGECSIAVHKQC 791
Cdd:cd20835     19 QPTYCSHCKDFIWGVIGkQGYQCQVCTCVVHKRC 52
SH3_ASPP cd11807
Src homology 3 domain of Apoptosis Stimulating of p53 proteins (ASPP); The ASPP family of ...
 941-989 2.43e-05

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


Pssm-ID: 212741 [Multi-domain]  Cd Length: 57  Bit Score: 42.75  E-value: 2.43e-05
                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|
gi 1946280069  941 AEFDFNPSESNQLPLRKGCQVIVLSKEGDY-KGWWKGKVQDRVGFFPKDY 989
Cdd:cd11807      5 ALFDYEAENGDELSFREGDELTVLRKGDDDeTEWWWARLNDKEGYVPRNL 54
C1_cPKC_rpt2 cd20836
second protein kinase C conserved region 1 (C1 domain) found in the classical (or conventional) ...
 757-794 2.43e-05

second protein kinase C conserved region 1 (C1 domain) found in the classical (or conventional) protein kinase C (cPKC) family; PKCs are classified into three groups (classical, atypical, and novel) depending on their mode of activation and the structural characteristics of their regulatory domain. cPKCs are potent kinases for histones, myelin basic protein, and protamine. They depend on calcium, DAG (1,2-diacylglycerol), and in most cases, phosphatidylserine (PS) for activation. There are four cPKC isoforms, named alpha, betaI, betaII, and gamma. PKC-alpha is expressed in many tissues and is associated with cell proliferation, apoptosis, and cell motility. It plays a role in the signaling of the growth factors PDGF, VEGF, EGF, and FGF. Abnormal levels of PKC-alpha have been detected in many transformed cell lines and several human tumors. In addition, PKC-alpha is required for HER2 dependent breast cancer invasion. The PKC beta isoforms (I and II), generated by alternative splicing of a single gene, are preferentially activated by hyperglycemia-induced DAG (1,2-diacylglycerol) in retinal tissues. This is implicated in diabetic microangiopathy such as ischemia, neovascularization, and abnormal vasodilator function. PKC-beta also plays an important role in VEGF signaling. In addition, glucose regulates proliferation in retinal endothelial cells via PKC-betaI. PKC-beta is also being explored as a therapeutic target in cancer. It contributes to tumor formation and is involved in the tumor host mechanisms of inflammation and angiogenesis. PKC-gamma is mainly expressed in neuronal tissues. It plays a role in protection from ischemia. Members of this family contain two copies of C1 domain. This model corresponds to the second one. The C1 domain is a cysteine-rich zinc binding domain that does not bind DNA nor possess structural similarity to conventional zinc finger domains; it contains two separate Zn(2+)-binding sites.


Pssm-ID: 410386  Cd Length: 54  Bit Score: 42.71  E-value: 2.43e-05
                           10        20        30
                   ....*....|....*....|....*....|....*...
gi 1946280069  757 YLQATTCHHCSKFLKGIILQGYLCGECSIAVHKQCIEF 794
Cdd:cd20836      8 YSSPTFCDHCGSLLYGLIHQGMKCDTCDMNVHKRCVKN 45
PH cd00821
Pleckstrin homology (PH) domain; PH domains have diverse functions, but in general are ...
 588-685 2.44e-05

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


Pssm-ID: 275388 [Multi-domain]  Cd Length: 92  Bit Score: 44.07  E-value: 2.44e-05
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1946280069  588 KDGELKIKAHDDQKI-KTRYIFVFDQVIIMCKSLRGETYSYRESLRLQEykiedvHTRRTLRTDARWSYQFYLVRKSERT 666
Cdd:cd00821      1 KEGYLLKRGGGGLKSwKKRWFVLFEGVLLYYKSKKDSSYKPKGSIPLSG------ILEVEEVSPKERPHCFELVTPDGRT 74

                           90
                   ....*....|....*....
gi 1946280069  667 aYTLYARTEDNKRKWMKAI 685
Cdd:cd00821     75 -YYLQADSEEERQEWLKAL 92
PH2_Kalirin_Trio_p63RhoGEF cd13241
p63RhoGEF pleckstrin homology (PH) domain, repeat 2; The guanine nucleotide exchange factor ...
 584-691 3.30e-05

p63RhoGEF pleckstrin homology (PH) domain, repeat 2; The guanine nucleotide exchange factor p63RhoGEF is an effector of the heterotrimeric G protein, Galphaq and linking Galphaq-coupled receptors (GPCRs) to the activation of RhoA. The Dbl(DH) and PH domains of p63RhoGEF interact with the effector-binding site and the C-terminal region of Galphaq and appear to relieve autoinhibition of the catalytic DH domain by the PH domain. Trio, Duet, and p63RhoGEF are shown to constitute a family of Galphaq effectors that appear to activate RhoA both in vitro and in intact cells. Dbs is a guanine nucleotide exchange factor (GEF), which contains spectrin repeats, a rhoGEF (DH) domain and a PH domain. The Dbs PH domain participates in binding to both the Cdc42 and RhoA GTPases. Trio plays an essential role in regulating the actin cytoskeleton during axonal guidance and branching. Trio is a multidomain signaling protein that contains two RhoGEF(DH)-PH domains in tandem. PH domains have diverse functions, but in general are involved in targeting proteins to the appropriate cellular location or in the interaction with a binding partner. They share little sequence conservation, but all have a common fold, which is electrostatically polarized. Less than 10% of PH domains bind phosphoinositide phosphates (PIPs) with high affinity and specificity. PH domains are distinguished from other PIP-binding domains by their specific high-affinity binding to PIPs with two vicinal phosphate groups: PtdIns(3,4)P2, PtdIns(4,5)P2 or PtdIns(3,4,5)P3 which results in targeting some PH domain proteins to the plasma membrane. A few display strong specificity in lipid binding. Any specificity is usually determined by loop regions or insertions in the N-terminus of the domain, which are not conserved across all PH domains. PH domains are found in cellular signaling proteins such as serine/threonine kinase, tyrosine kinases, regulators of G-proteins, endocytotic GTPases, adaptors, as well as cytoskeletal associated molecules and in lipid associated enzymes.


Pssm-ID: 270061  Cd Length: 140  Bit Score: 44.94  E-value: 3.30e-05
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1946280069  584 GRLLKDGelKIKAHDD-----------QKIKTRYIFVFDQVIIMCKSLRGET------YSYRESLRLQEYKIEDVHTRRT 646
Cdd:cd13241      9 GKITAQG--KLLLQGTllvsepsagllQKGKERRVFLFEQIIIFSEILGKKTqfsnpgYIYKNHIKVNKMSLEENVDGDP 86

                           90       100       110       120
                   ....*....|....*....|....*....|....*....|....*...
gi 1946280069  647 LRtdarwsyqFYLV---RKSERTAYTLYARTEDNKRKWMKAIHDAMDN 691
Cdd:cd13241     87 LR--------FALKsrdPNNPSETFILQAASPEVRQEWVDTINQILDT 126
SH3_STAM2 cd11963
Src homology 3 domain of Signal Transducing Adaptor Molecule 2; STAM2, also called EAST ...
 935-994 3.51e-05

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


Pssm-ID: 212896 [Multi-domain]  Cd Length: 57  Bit Score: 42.31  E-value: 3.51e-05
                           10        20        30        40        50        60
                   ....*....|....*....|....*....|....*....|....*....|....*....|
gi 1946280069  935 RRIIAIaeFDFNPSESNQLPLRKGCQVIVLSKEGdyKGWWKGKVQDRVGFFPKDYVRETL 994
Cdd:cd11963      2 RKVRAL--YDFEAVEDNELTFKHGEIIIVLDDSD--ANWWKGENHRGVGLFPSNFVTTDL 57
PH_SOS cd01261
Son of Sevenless (SOS) Pleckstrin homology (PH) domain; SOS is a Ras guanine nucleotide ...
 586-685 3.76e-05

Son of Sevenless (SOS) Pleckstrin homology (PH) domain; SOS is a Ras guanine nucleotide exchange factor. SOS is thought to transmit signals from activated receptor tyrosine kinases to the Ras signaling pathway. SOS contains a histone domain, Dbl-homology (DH), a PH domain, Rem domain, Cdc25 domain, and a Grb2 binding domain. The SOS PH domain binds to phosphatidylinositol-4,5-bisphosphate (PIP2) and phosphatidic acid (PA). SOS is dependent on Ras binding to the allosteric site via its histone domain for both a lower level of activity (Ras GDP) and maximal activity (Ras GTP). The DH domain blocks the allosteric Ras binding site in SOS. The PH domain is closely associated with the DH domain and the action of the DH-PH unit gates a reciprocal interaction between Ras and SOS. The C-terminal proline-rich domain of SOS binds to the adapter protein Grb2 which localizes the Sos protein to the plasma membrane and diminishes the negative effect of the C-terminal domain on the guanine nucleotide exchange activity of the CDC25-homology domain of SOS. PH domains have diverse functions, but in general are involved in targeting proteins to the appropriate cellular location or in the interaction with a binding partner. They share little sequence conservation, but all have a common fold, which is electrostatically polarized. Less than 10% of PH domains bind phosphoinositide phosphates (PIPs) with high affinity and specificity. PH domains are distinguished from other PIP-binding domains by their specific high-affinity binding to PIPs with two vicinal phosphate groups: PtdIns(3,4)P2, PtdIns(4,5)P2 or PtdIns(3,4,5)P3 which results in targeting some PH domain proteins to the plasma membrane. A few display strong specificity in lipid binding. Any specificity is usually determined by loop regions or insertions in the N-terminus of the domain, which are not conserved across all PH domains. PH domains are found in cellular signaling proteins such as serine/threonine kinase, tyrosine kinases, regulators of G-proteins, endocytotic GTPases, adaptors, as well as cytoskeletal associated molecules and in lipid associated enzymes.


Pssm-ID: 269963  Cd Length: 109  Bit Score: 43.89  E-value: 3.76e-05
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1946280069  586 LLKDGELKIKAHDDQKIKtRYIFVFDQVIIMCKSLRGETysyRESLRLQEYKI-EDVHTRRTL---RTDARWSYQFYLVR 661
Cdd:cd01261      6 FIMEGTLGKVGSGKRKTE-RHAFLFDGLLLLCKSNRRRT---STGGPKPEYRLkEKFFIRKVEindLEDTEELKNAFEIV 81

                           90       100
                   ....*....|....*....|....
gi 1946280069  662 KSERTAYTLYARTEDNKRKWMKAI 685
Cdd:cd01261     82 PRDQPSVILFAKSAEEKNNWMAAL 105
PH_RhoGEF3_XPLN cd10572
Rho guanine nucleotide exchange factor 3 Pleckstrin homology (PH) domain; RhoGEF3/XPLN, a Rho ...
 585-689 4.09e-05

Rho guanine nucleotide exchange factor 3 Pleckstrin homology (PH) domain; RhoGEF3/XPLN, a Rho family GEF, preferentially stimulates guanine nucleotide exchange on RhoA and RhoB, but not RhoC, RhoG, Rac1, or Cdc42 in vitro. It also possesses transforming activity. RhoGEF3/XPLN contains a tandem Dbl homology and PH domain, but lacks homology with other known functional domains or motifs. It is expressed in the brain, skeletal muscle, heart, kidney, platelets, and macrophage and neuronal cell lines. PH domains have diverse functions, but in general are involved in targeting proteins to the appropriate cellular location or in the interaction with a binding partner. They share little sequence conservation, but all have a common fold, which is electrostatically polarized. Less than 10% of PH domains bind phosphoinositide phosphates (PIPs) with high affinity and specificity. PH domains are distinguished from other PIP-binding domains by their specific high-affinity binding to PIPs with two vicinal phosphate groups: PtdIns(3,4)P2, PtdIns(4,5)P2 or PtdIns(3,4,5)P3 which results in targeting some PH domain proteins to the plasma membrane. A few display strong specificity in lipid binding. Any specificity is usually determined by loop regions or insertions in the N-terminus of the domain, which are not conserved across all PH domains. PH domains are found in cellular signaling proteins such as serine/threonine kinase, tyrosine kinases, regulators of G-proteins, endocytotic GTPases, adaptors, as well as cytoskeletal associated molecules and in lipid associated enzymes.


Pssm-ID: 269976  Cd Length: 133  Bit Score: 44.28  E-value: 4.09e-05
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1946280069  585 RLLKDGELKIKAhdDQKIktrYIFVFDQVIIMCKSL-RGETYSY---RESLRLQEYKIEDVH--------TRRTLRTDAR 652
Cdd:cd10572     19 LLLCHGELKNNR--GTKL---HVFLFEEVLVLTRPVtRNEQLCYqvyRQPIPVADLVLEDLPdgevrlggSFRGAFSNNE 93

                           90       100       110       120
                   ....*....|....*....|....*....|....*....|
gi 1946280069  653 WSYQFYLVRKSERT---AYTLYARTEDNKRKWMKAIHDAM 689
Cdd:cd10572     94 RAKNFFRVSFTDRSlgqSHTLQANDEFDKQQWLNCIRQAV 133
SH2_Cterm_RasGAP cd10354
C-terminal Src homology 2 (SH2) domain found in Ras GTPase-activating protein 1 (GAP); RasGAP ...
 831-914 4.22e-05

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


Pssm-ID: 198217  Cd Length: 77  Bit Score: 42.80  E-value: 4.22e-05
                           10        20        30        40        50        60        70        80
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gi 1946280069  831 WFVGEMGRDRASALL-ERHMDGTYLlrVRPQgATHPNEtiYALSLKTDDRVKHMKVyerTMEGVPHYFLSeSRFFRSITD 909
Cdd:cd10354      2 WFHGKISREEAYNMLvKVGGPGSFL--VRES-DNTPGD--YSLSFRVNEGIKHFKI---IPTGNNQFMMG-GRYFSSLDD 72


                   ....*
gi 1946280069  910 LIGCY 914
Cdd:cd10354     73 VIDRY 77
SH3_Sorbs2_2 cd11923
Second Src Homology 3 domain of Sorbin and SH3 domain containing 2 (Sorbs2), also called ...
 939-990 4.28e-05

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


Pssm-ID: 212856 [Multi-domain]  Cd Length: 57  Bit Score: 42.21  E-value: 4.28e-05
                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....
gi 1946280069  939 AIAEFDFNPSESNQLPLRKGCQVIVLsKEGDyKGWWKGKV--QDRVGFFPKDYV 990
Cdd:cd11923      3 AVAKYNFNADTNVELSLRKGDRVVLL-KQVD-QNWYEGKIpgTNRQGIFPVSYV 54
C1_PKD2_rpt2 cd20843
second protein kinase C conserved region 1 (C1 domain) found in protein kinase D2 (PKD2) and ...
 757-791 4.52e-05

second protein kinase C conserved region 1 (C1 domain) found in protein kinase D2 (PKD2) and similar proteins; PKD2, also called PRKD2, HSPC187, or serine/threonine-protein kinase D2 (nPKC-D2), is a serine/threonine-protein kinase that converts transient diacylglycerol (DAG) signals into prolonged physiological effects downstream of PKC, and is involved in the regulation of cell proliferation via MAPK1/3 (ERK1/2) signaling, oxidative stress-induced NF-kappa-B activation, inhibition of HDAC7 transcriptional repression, signaling downstream of T-cell antigen receptor (TCR) and cytokine production, and plays a role in Golgi membrane trafficking, angiogenesis, secretory granule release and cell adhesion. PKD2 contains N-terminal tandem cysteine-rich zinc binding C1 (PKC conserved region 1), central PH (Pleckstrin Homology), and C-terminal catalytic kinase domains. This model corresponds to the second C1 domain. The C1 domain is a cysteine-rich zinc binding domain that does not bind DNA nor possess structural similarity to conventional zinc finger domains; it contains two separate Zn(2+)-binding sites.


Pssm-ID: 410393  Cd Length: 79  Bit Score: 42.65  E-value: 4.52e-05
                           10        20        30
                   ....*....|....*....|....*....|....*
gi 1946280069  757 YLQATTCHHCSKFLKGIILQGYLCGECSIAVHKQC 791
Cdd:cd20843     19 YTRPTVCQFCKKLLKGLFRQGLQCKDCKFNCHKRC 53
CH_betaPIX cd21266
calponin homology (CH) domain found in beta-Pak Interactive eXchange factor; Beta-Pak ...
 17-130 4.98e-05

calponin homology (CH) domain found in beta-Pak Interactive eXchange factor; Beta-Pak Interactive eXchange factor (beta-PIX), also called PAK-interacting exchange factor beta, Rho guanine nucleotide exchange factor 7 (ARHGEF7), p85, or Cool (Cloned out of Library)-1, activates small GTPases by exchanging bound GDP for free GTP. It acts as a GEF for both Cdc42 and Rac1, and plays important roles in regulating neuroendocrine exocytosis, focal adhesion maturation, cell migration, synaptic vesicle localization, and insulin secretion. Beta-PIX contains a single copy of the CH domain at its N-terminus. CH domains are actin filament (F-actin) binding motifs.


Pssm-ID: 409115  Cd Length: 112  Bit Score: 43.75  E-value: 4.98e-05
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1946280069   17 SWKECVEWLTRCDVLRRDHKT-NWPEASvidLANTLRDGVLLCNLLNVLDPGCIDlkDVNQKPQlAQFLCLRNIKTFLQT 95
Cdd:cd21266      1 SAEQTVTWLITLGVLESPKKTiSDPEGF---LQASLKDGVVLCRLLERLLPGSID--KVYPEPR-TESECLSNIREFLRG 74

                           90       100       110
                   ....*....|....*....|....*....|....*
gi 1946280069   96 ChdifGLKENDLFEPSMLFELNDFFKVLNTLSKLS 130
Cdd:cd21266     75 C----GALRLETFDANDLYQGQNFNKVLSSLVALN 105
CH smart00033
Calponin homology domain; Actin binding domains present in duplicate at the N-termini of ...
 19-129 5.09e-05

Calponin homology domain; Actin binding domains present in duplicate at the N-termini of spectrin-like proteins (including dystrophin, alpha-actinin). These domains cross-link actin filaments into bundles and networks. A calponin homology domain is predicted in yeasst Cdc24p.


Pssm-ID: 214479 [Multi-domain]  Cd Length: 101  Bit Score: 43.46  E-value: 5.09e-05
                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1946280069    19 KECVEWLtrcdvlrRDHKTNWPEASVIDLANTLRDGVLLCNLLNVLDPGCIDLKDVNqkPQLAQFLCLRNIKTFLQTCHD 98
Cdd:smart00033    1 KTLLRWV-------NSLLAEYDKPPVTNFSSDLKDGVALCALLNSLSPGLVDKKKVA--ASLSRFKKIENINLALSFAEK 71

                            90       100       110
                    ....*....|....*....|....*....|..
gi 1946280069    99 IFGlkENDLFEPSMLFE-LNDFFKVLNTLSKL 129
Cdd:smart00033   72 LGG--KVVLFEPEDLVEgPKLILGVIWTLISL 101
SH3_srGAP cd11809
Src homology 3 domain of Slit-Robo GTPase Activating Proteins; Slit-Robo GTPase Activating ...
 939-990 6.05e-05

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


Pssm-ID: 212743 [Multi-domain]  Cd Length: 53  Bit Score: 41.62  E-value: 6.05e-05
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gi 1946280069  939 AIAEFDFNPSESNQLPLRKGCQVIVLSKEGDYkgWWKGKVQDRVGFFPKDYV 990
Cdd:cd11809      2 ATAQFDYTGRSERELSFKKGDSLTLYRQVSDD--WWRGQLNGQDGLVPHKYI 51
SH3_CD2AP_2 cd12054
Second Src Homology 3 domain (SH3B) of CD2-associated protein; CD2AP, also called CMS (Cas ...
 943-992 7.36e-05

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


Pssm-ID: 212987 [Multi-domain]  Cd Length: 55  Bit Score: 41.49  E-value: 7.36e-05
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gi 1946280069  943 FDFNPSESNQLPLRKGcQVIVLSKEGDyKGWWKGKVQDRVGFFPKDYVRE 992
Cdd:cd12054      7 FEYVPQNEDELELKVG-DIIDINEEVE-EGWWSGTLNGKSGLFPSNFVKE 54
SH3_Shank cd11832
Src homology 3 domain of SH3 and multiple ankyrin repeat domains (Shank) proteins; Shank ...
 940-988 7.96e-05

Src homology 3 domain of SH3 and multiple ankyrin repeat domains (Shank) proteins; Shank proteins carry scaffolding functions through multiple sites of protein-protein interaction in its domain architecture, including ankyrin (ANK) repeats, a long proline rich region, as well as SH3, PDZ, and SAM domains. They bind a variety of membrane and cytosolic proteins, and exist in alternatively spliced isoforms. They are highly enriched in postsynaptic density (PSD) where they interact with the cytoskeleton and with postsynaptic membrane receptors including NMDA and glutamate receptors. They are crucial in the construction and organization of the PSD and dendritic spines of excitatory synapses. There are three members of this family (Shank1, Shank2, Shank3) which show distinct and cell-type specific patterns of expression. Shank1 is brain-specific; Shank2 is found in neurons, glia, endocrine cells, liver, and kidney; Shank3 is widely expressed. The SH3 domain of Shank binds GRIP, a scaffold protein that binds AMPA receptors and Eph receptors/ligands. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 212766  Cd Length: 50  Bit Score: 41.27  E-value: 7.96e-05
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gi 1946280069  940 IAEFDFNPSESNQLPLRKGCQVIVLSKeGDYkGWWKGKVQDRVGFFPKD 988
Cdd:cd11832      3 IAVKSYSPQEEGEISLHKGDRVKVLSI-GEG-GFWEGSVRGRTGWFPSD 49
C1_VAV1 cd20867
protein kinase C conserved region 1 (C1 domain) found in VAV1 protein; VAV1 is expressed ...
 759-792 8.48e-05

protein kinase C conserved region 1 (C1 domain) found in VAV1 protein; VAV1 is expressed predominantly in the hematopoietic system and 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. This model corresponds to the C1 domain. The C1 domain is a cysteine-rich zinc binding domain that does not bind DNA nor possess structural similarity to conventional zinc finger domains; it contains two separate Zn(2+)-binding sites.


Pssm-ID: 410417  Cd Length: 57  Bit Score: 41.47  E-value: 8.48e-05
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gi 1946280069  759 QATTCHHCSKFLKGIILQGYLCGECSIAVHKQCI 792
Cdd:cd20867     16 ETTSCKACQMLLRGTFYQGYRCHRCRAPAHKECL 49
SH3_SKAP2 cd12045
Src Homology 3 domain of Src Kinase-Associated Phosphoprotein 2; SKAP2, also called ...
 943-990 1.01e-04

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


Pssm-ID: 212978  Cd Length: 53  Bit Score: 41.04  E-value: 1.01e-04
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gi 1946280069  943 FDFNPSESNQLPLRKGCQVIVLSKEGDYKGWWKGKVQDRVGFFPKDYV 990
Cdd:cd12045      6 WDCTGDQPDELSFKRGDTIYILSKEYNRFGWWVGEMKGTIGLVPKAYI 53
SH3_Abl cd11850
Src homology 3 domain of the Protein Tyrosine Kinase, Abelson kinase; Abl (or c-Abl) is a ...
 940-990 1.03e-04

Src homology 3 domain of the Protein Tyrosine Kinase, Abelson kinase; Abl (or c-Abl) is a ubiquitously-expressed cytoplasmic (or nonreceptor) PTK that contains SH3, SH2, and tyr kinase domains in its N-terminal region, as well as nuclear localization motifs, a putative DNA-binding domain, and F- and G-actin binding domains in its C-terminal tail. It also contains a short autoinhibitory cap region in its N-terminus. Abl function depends on its subcellular localization. In the cytoplasm, Abl plays a role in cell proliferation and survival. In response to DNA damage or oxidative stress, Abl is transported to the nucleus where it induces apoptosis. In chronic myelogenous leukemia (CML) patients, an aberrant translocation results in the replacement of the first exon of Abl with the BCR (breakpoint cluster region) gene. The resulting BCR-Abl fusion protein is constitutively active and associates into tetramers, resulting in a hyperactive kinase sending a continuous signal. This leads to uncontrolled proliferation, morphological transformation and anti-apoptotic effects. BCR-Abl is the target of selective inhibitors, such as imatinib (Gleevec), used in the treatment of CML. Abl2, also known as ARG (Abelson-related gene), is thought to play a cooperative role with Abl in the proper development of the nervous system. The Tel-ARG fusion protein, resulting from reciprocal translocation between chromosomes 1 and 12, is associated with acute myeloid leukemia (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: 212784  Cd Length: 56  Bit Score: 41.24  E-value: 1.03e-04
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gi 1946280069  940 IAEFDFNPSESNQLPLRKGCQVIVLSKEGDykGWW---KGKVQDRVGFFPKDYV 990
Cdd:cd11850      3 VALYDFVASGENQLSIKKGEQLRVLGYNKN--GEWceaESKSTGGQGWVPSNYI 54
C1_nPKC_theta-like_rpt2 cd20837
second protein kinase C conserved region 1 (C1 domain) found in novel protein kinase C (nPKC) ...
 757-791 1.07e-04

second protein kinase C conserved region 1 (C1 domain) found in novel protein kinase C (nPKC) theta, delta, and similar proteins; PKCs are classified into three groups (classical, atypical, and novel) depending on their mode of activation and the structural characteristics of their regulatory domain. nPKCs are calcium-independent, but require DAG (1,2-diacylglycerol) and phosphatidylserine (PS) for activity. PKC-theta is selectively expressed in T-cells and plays an important and non-redundant role in several aspects of T-cell biology. PKC-delta plays a role in cell cycle regulation and programmed cell death in many cell types. Members of this family contain two copies of C1 domain. This model corresponds to the second one. The C1 domain is a cysteine-rich zinc binding domain that does not bind DNA nor possess structural similarity to conventional zinc finger domains; it contains two separate Zn(2+)-binding sites.


Pssm-ID: 410387  Cd Length: 50  Bit Score: 40.88  E-value: 1.07e-04
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gi 1946280069  757 YLQATTCHHCSKFLKGIILQGYLCGECSIAVHKQC 791
Cdd:cd20837      8 YMSPTFCDHCGSLLWGLFRQGLKCEECGMNVHHKC 42
SH3_CIN85_3 cd12057
Third Src Homology 3 domain (SH3C) of Cbl-interacting protein of 85 kDa; CIN85, also called ...
 943-991 1.16e-04

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


Pssm-ID: 212990 [Multi-domain]  Cd Length: 56  Bit Score: 41.04  E-value: 1.16e-04
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gi 1946280069  943 FDFNPSESNQLPLRKGCQVIVLSKEGDYKGWWKGKVQDRVGFFPKDYVR 991
Cdd:cd12057      6 FPYEAQNEDELTIKEGDIVTLISKDCIDAGWWEGELNGRRGVFPDNFVK 54
SH2_C-SH2_PLC_gamma_like cd09932
C-terminal Src homology 2 (C-SH2) domain in Phospholipase C gamma; Phospholipase C gamma is a ...
 831-933 1.22e-04

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


Pssm-ID: 198186  Cd Length: 104  Bit Score: 42.25  E-value: 1.22e-04
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gi 1946280069  831 WFVGEMGRDRASALLER-HMDGTYLLRVRPQGathPNetIYALSLKTDDRVKHMKVyerTMEGvPHYFLSESRFFrSITD 909
Cdd:cd09932      6 WFHANLTREQAEEMLMRvPRDGAFLVRPSETD---PN--SFAISFRAEGKIKHCRI---KQEG-RLFVIGTSQFE-SLVE 75

                           90       100
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gi 1946280069  910 LIGCYEHSSLGENfvgldVTLKWP 933
Cdd:cd09932     76 LVSYYEKHPLYRK-----IKLRYP 94
SH2_SHB_SHD_SHE_SHF_like cd09945
Src homology 2 domain found in SH2 domain-containing adapter proteins B, D, E, and F (SHB, SHD, ...
 831-919 1.22e-04

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


Pssm-ID: 198198  Cd Length: 98  Bit Score: 42.03  E-value: 1.22e-04
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gi 1946280069  831 WFVGEMGRDRASALLERHMDGTYLLRvrpQGATHPNEtiYALSLKTDDRVKHMKVyERTMEGvpHYFLSE-SRFFRSITD 909
Cdd:cd09945      3 WYHGAITRIEAESLLRPCKEGSYLVR---NSESTKQD--YSLSLKSAKGFMHMRI-QRNETG--QYILGQfSRPFETIPE 74

                           90       100
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gi 1946280069  910 LIGCY----------EHSSL 919
Cdd:cd09945     75 MIRHYclnklpvrgaEHMCL 94
SH2_Nck_family cd09943
Src homology 2 (SH2) domain found in the Nck family; Nck proteins are adaptors that modulate ...
 831-917 1.33e-04

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


Pssm-ID: 198196  Cd Length: 93  Bit Score: 41.73  E-value: 1.33e-04
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gi 1946280069  831 WFVGEMGRDRASALL-ERHMDGTYLLRvrpQGATHPNEtiYALSLKTDDRVKHMKVyeRTMEGVphyFLSESRFFRSITD 909
Cdd:cd09943      3 WYYGRITRHQAETLLnEHGHEGDFLIR---DSESNPGD--YSVSLKAPGRNKHFKV--QVVDNV---YCIGQRKFHTMDE 72


                   ....*...
gi 1946280069  910 LIGCYEHS 917
Cdd:cd09943     73 LVEHYKKA 80
C1_nPKC_epsilon-like_rpt2 cd20838
second protein kinase C conserved region 1 (C1 domain) found in novel protein kinase C (nPKC) ...
 756-791 1.44e-04

second protein kinase C conserved region 1 (C1 domain) found in novel protein kinase C (nPKC) epsilon, eta, and similar proteins; PKCs are classified into three groups (classical, atypical, and novel) depending on their mode of activation and the structural characteristics of their regulatory domain. nPKCs are calcium-independent, but require DAG (1,2-diacylglycerol) and phosphatidylserine (PS) for activity. PKC-epsilon has been shown to behave as an oncoprotein. Its overexpression contributes to neoplastic transformation depending on the cell type. It contributes to oncogenesis by inducing disordered cell growth and inhibiting cell death. It also plays a role in tumor invasion and metastasis. PKC-epsilon has also been found to confer cardioprotection against ischemia and reperfusion-mediated damage. Other cellular functions include the regulation of gene expression, cell adhesion, and cell motility. PKC-eta is predominantly expressed in squamous epithelia, where it plays a crucial role in the signaling of cell-type specific differentiation. It is also expressed in pro-B cells and early-stage thymocytes, and acts as a key regulator in early B-cell development. PKC-eta increases glioblastoma multiforme (GBM) proliferation and resistance to radiation, and is being developed as a therapeutic target for the management of GBM. Members of this family contain two copies of C1 domain. This model corresponds to the second one. The C1 domain is a cysteine-rich zinc binding domain that does not bind DNA nor possess structural similarity to conventional zinc finger domains; it contains two separate Zn(2+)-binding sites.


Pssm-ID: 410388  Cd Length: 55  Bit Score: 40.72  E-value: 1.44e-04
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gi 1946280069  756 MYLQATTCHHCSKFLKGIILQGYLCGECSIAVHKQC 791
Cdd:cd20838      9 NYKRPTFCDHCGSLLYGLYKQGLQCKVCKMNVHKRC 44
SH3_Endophilin_A cd11803
Src homology 3 domain of Endophilin-A; Endophilins play roles in synaptic vesicle formation, ...
 941-990 1.50e-04

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


Pssm-ID: 212737 [Multi-domain]  Cd Length: 55  Bit Score: 40.71  E-value: 1.50e-04
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gi 1946280069  941 AEFDFNPSESNQLPLRKGcQVIVLSKEGDyKGWWKGKVQDRVGFFPKDYV 990
Cdd:cd11803      5 ALYDFEPENEGELGFKEG-DIITLTNQID-ENWYEGMVNGQSGFFPVNYV 52
C1_Stac cd20817
protein kinase C conserved region 1 (C1 domain) found in the SH3 and cysteine-rich ...
 757-798 1.70e-04

protein kinase C conserved region 1 (C1 domain) found in the SH3 and cysteine-rich domain-containing protein (Stac) family; Stac proteins are putative adaptor proteins that are important for neuronal function. There are three mammalian members (Stac1, Stac2 and Stac3) of this family. Stac1 and Stac3 contain two SH3 domains while Stac2 contains a single SH3 domain at the C-terminus. Stac1 and Stac2 have been found to be expressed differently in mature dorsal root ganglia (DRG) neurons. Stac1 is mainly expressed in peptidergic neurons while Stac2 is found in a subset of nonpeptidergic and all trkB+ neurons. Stac proteins contain a cysteine-rich C1 domain and one or two SH3 domains at the C-terminus. This model corresponds to the C1 domain. The C1 domain is a cysteine-rich zinc binding domain that does not bind DNA nor possess structural similarity to conventional zinc finger domains; it contains two separate Zn(2+)-binding sites.


Pssm-ID: 410367  Cd Length: 51  Bit Score: 40.39  E-value: 1.70e-04
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gi 1946280069  757 YLQATTCHHCSKFLKGIILQGYLCGECSIAVHKQCIEFSGRC 798
Cdd:cd20817      8 FKKPTFCDVCKELLVGLSKQGLRCKNCKMNVHHKCQEGVPDC 49
SH3_MyoIe_If_like cd11827
Src homology 3 domain of Myosins Ie, If, and similar proteins; Myosins Ie (MyoIe) and If ...
 941-992 1.70e-04

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


Pssm-ID: 212761 [Multi-domain]  Cd Length: 53  Bit Score: 40.48  E-value: 1.70e-04
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gi 1946280069  941 AEFDFNPSESNQLPLRKGcQVIVLSKEgDYKGWWKGKVQDRVGFFPKDYVRE 992
Cdd:cd11827      4 ALYAYDAQDTDELSFNEG-DIIEILKE-DPSGWWTGRLRGKEGLFPGNYVEK 53
SH3_STAM cd11820
Src homology 3 domain of Signal Transducing Adaptor Molecules; STAMs were discovered as ...
 941-990 1.73e-04

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: 40.53  E-value: 1.73e-04
                           10        20        30        40        50
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gi 1946280069  941 AEFDFNPSESNQLPLRKGcQVIVLSKEGDyKGWWKGKVQDRVGFFPKDYV 990
Cdd:cd11820      5 ALYDFEAAEDNELTFKAG-EIITVLDDSD-PNWWKGSNHRGEGLFPANFV 52
C1_MRCK cd20809
protein kinase C conserved region 1 (C1 domain) found in the Myotonic dystrophy kinase-related ...
 761-793 1.82e-04

protein kinase C conserved region 1 (C1 domain) found in the Myotonic dystrophy kinase-related Cdc42-binding kinase (MRCK) family; MRCK is thought to be a coincidence detector of signaling by the small GTPase Cdc42 and phosphoinositides. MRCK/Cdc42 signaling mediates myosin-dependent cell motility. MRCK has been shown to promote cytoskeletal reorganization, which affects many biological processes. Three isoforms of MRCK are known, named alpha, beta and gamma. MRCKgamma is expressed in heart and skeletal muscles, unlike MRCKalpha and MRCKbeta, which are expressed ubiquitously. MRCK consists of a serine/threonine kinase domain, a cysteine rich (C1) region, a PH domain and a p21 binding motif. This model corresponds to C1 domain. The C1 domain is a cysteine-rich zinc binding domain that does not bind DNA nor possess structural similarity to conventional zinc finger domains; it contains two separate Zn(2+)-binding sites.


Pssm-ID: 410359  Cd Length: 53  Bit Score: 40.33  E-value: 1.82e-04
                           10        20        30
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gi 1946280069  761 TTCHHCSKFLKGIILQGYLCGECSIAVHKQCIE 793
Cdd:cd20809     12 TKCNHCTSLMVGLVRQGLVCEVCGYACHVSCAD 44
SH3_Shank3 cd11984
Src homology 3 domain of SH3 and multiple ankyrin repeat domains protein 3; Shank3, also ...
 935-990 1.83e-04

Src homology 3 domain of SH3 and multiple ankyrin repeat domains protein 3; Shank3, also called ProSAP2 (Proline-rich synapse-associated protein 2), is widely expressed. It plays a role in the formation of dendritic spines and synapses. Haploinsufficiency of the Shank3 gene causes the 22q13 deletion/Phelan-McDermid syndrome, and variants of Shank3 have been implicated in autism spectrum disorder, schizophrenia, and intellectual disability. Shank proteins carry scaffolding functions through multiple sites of protein-protein interaction in its domain architecture, including ankyrin (ANK) repeats, a long proline rich region, as well as SH3, PDZ, and SAM domains. The SH3 domain of Shank binds GRIP, a scaffold protein that binds AMPA receptors and Eph receptors/ligands. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 212917  Cd Length: 52  Bit Score: 40.32  E-value: 1.83e-04
                           10        20        30        40        50
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gi 1946280069  935 RRIIAIAEFDfnPSESNQLPLRKGCQVIVLS-KEGdykGWWKGKVQDRVGFFPKDYV 990
Cdd:cd11984      1 RTFIAVKAYS--PQGEGEIQLNRGERVKVLSiGEG---GFWEGTVKGRTGWFPADCV 52
PH1_FDG4 cd15791
FYVE, RhoGEF and PH domain containing/faciogenital dysplasia proteins 4, N-terminal Pleckstrin ...
 586-685 1.87e-04

FYVE, RhoGEF and PH domain containing/faciogenital dysplasia proteins 4, N-terminal Pleckstrin homology (PH) domain; In general, FGDs have a RhoGEF (DH) domain, followed by an N-terminal PH domain, a FYVE domain and a C-terminal PH domain. All FGDs are guanine nucleotide exchange factors that activates the Rho GTPase Cdc42, an important regulator of membrane trafficking. The RhoGEF domain is responsible for GEF catalytic activity, while the N-terminal PH domain is involved in intracellular targeting of the DH domain. FGD4 is one of the genes associated with Charcot-Marie-Tooth neuropathy type 4 (CMT4), a group of progressive motor and sensory axonal and demyelinating neuropathies that are distinguished from other forms of CMT by autosomal recessive inheritance. Those affected have distal muscle weakness and atrophy associated with sensory loss and, frequently, pes cavus foot deformity. PH domains have diverse functions, but in general are involved in targeting proteins to the appropriate cellular location or in the interaction with a binding partner. They share little sequence conservation, but all have a common fold, which is electrostatically polarized. Less than 10% of PH domains bind phosphoinositide phosphates (PIPs) with high affinity and specificity. PH domains are distinguished from other PIP-binding domains by their specific high-affinity binding to PIPs with two vicinal phosphate groups: PtdIns(3,4)P2, PtdIns(4,5)P2 or PtdIns(3,4,5)P3 which results in targeting some PH domain proteins to the plasma membrane. A few display strong specificity in lipid binding. Any specificity is usually determined by loop regions or insertions in the N-terminus of the domain, which are not conserved across all PH domains. PH domains are found in cellular signaling proteins such as serine/threonine kinase, tyrosine kinases, regulators of G-proteins, endocytotic GTPases, adaptors, as well as cytoskeletal associated molecules and in lipid associated enzymes.


Pssm-ID: 275434  Cd Length: 94  Bit Score: 41.52  E-value: 1.87e-04
                           10        20        30        40        50        60        70        80
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gi 1946280069  586 LLKDGELKIKAHDDQKIKTRYIFVFDQVIIMCK---SLRGETYSYRESLRLQEYKIEDvhtrrTLRTDARWSYQfylVRK 662
Cdd:cd15791      1 LIKEGQILKLAARNTSAQERYLFLFNNMLLYCVpkfSLVGSKYTVRTRIGIDGMKVVE-----TQNEDYPHTFQ---VSG 72

                           90       100
                   ....*....|....*....|...
gi 1946280069  663 SERTaYTLYARTEDNKRKWMKAI 685
Cdd:cd15791     73 KERT-LELQASSEQDKEEWIKAL 94
SH3_iASPP cd11952
Src Homology 3 (SH3) domain of Inhibitor of ASPP protein (iASPP); iASPP, also called ...
 941-989 1.96e-04

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


Pssm-ID: 212885 [Multi-domain]  Cd Length: 56  Bit Score: 40.30  E-value: 1.96e-04
                           10        20        30        40
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gi 1946280069  941 AEFDFNPSESNQLPLRKGCQVIVLSKEGDYKGWWKGKVQDRVGFFPKDY 989
Cdd:cd11952      5 ALWDYSAEFPDELSFKEGDMVTVLRKDGEGTDWWWASLCGREGYVPRNY 53
SH3_GRAP2_C cd11950
C-terminal Src homology 3 domain of GRB2-related adaptor protein 2; GRAP2 is also called GADS ...
 939-991 1.99e-04

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


Pssm-ID: 212883 [Multi-domain]  Cd Length: 53  Bit Score: 40.19  E-value: 1.99e-04
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gi 1946280069  939 AIAEFDFNPSESNQLPLRKGCQVIVLSKEGDYkgWWKGKVQDRVGFFPKDYVR 991
Cdd:cd11950      2 VRALYDFEALEDDELGFNSGDVIEVLDSSNPS--WWKGRLHGKLGLFPANYVA 52
SH2_csk_like cd09937
Src homology 2 (SH2) domain found in Carboxyl-Terminal Src Kinase (Csk); Both the C-terminal ...
 831-915 2.02e-04

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


Pssm-ID: 198190  Cd Length: 98  Bit Score: 41.51  E-value: 2.02e-04
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gi 1946280069  831 WFVGEMGRDRASALLERHMDGTYLLRvrpQGATHPNEtiYALSLKTDDRVKHMKVYERtmEGvpHYFLSESRFFRSITDL 910
Cdd:cd09937      5 WFHGKISREEAERLLQPPEDGLFLVR---ESTNYPGD--YTLCVSFEGKVEHYRVIYR--NG--KLTIDEEEYFENLIQL 75


                   ....*
gi 1946280069  911 IGCYE 915
Cdd:cd09937     76 VEHYT 80
SH3_Intersectin2_5 cd11996
Fifth Src homology 3 domain (or SH3E) of Intersectin-2; Intersectin-2 (ITSN2) is an adaptor ...
 940-991 2.29e-04

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: 39.96  E-value: 2.29e-04
                           10        20        30        40        50
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gi 1946280069  940 IAEFDFNPSESNQLPLRKGCQVIVLSKegDYKGWWKGKVQDRVGFFPKDYVR 991
Cdd:cd11996      4 IAMYDYTANNEDELSFSKGQLINVLNK--DDPDWWQGEINGVTGLFPSNYVK 53
SH3_ARHGEF9_like cd11828
Src homology 3 domain of ARHGEF9-like Rho guanine nucleotide exchange factors; Members of this ...
 939-991 2.34e-04

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


Pssm-ID: 212762 [Multi-domain]  Cd Length: 53  Bit Score: 40.06  E-value: 2.34e-04
                           10        20        30        40        50
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gi 1946280069  939 AIAEFDFNPSESNQLPLRKGCQVIVLskEGDYKGWWKGKVQDRVGFFPKDYVR 991
Cdd:cd11828      2 AEALWDHVTMDPEELGFKAGDVIEVL--DMSDKDWWWGSIRDEEGWFPASFVR 52
CH_PIX cd21202
calponin homology (CH) domain found in the Pak Interactive eXchange factor family; Pak ...
 19-131 2.40e-04

calponin homology (CH) domain found in the Pak Interactive eXchange factor family; Pak Interactive eXchange factor (PIX) proteins are Rho guanine nucleotide exchange factors (GEFs), which activate small GTPases by exchanging bound GDP for free GTP. They act as GEFs for both Cdc42 and Rac1, and have been implicated in cell motility, adhesion, neurite outgrowth, and cell polarity. Vertebrates contain two proteins from the PIX family, alpha-PIX and beta-PIX. Alpha-PIX, also called Rho guanine nucleotide exchange factor 6 (ARHGEF6), is localized in dendritic spines where it regulates spine morphogenesis. It controls dendritic length and spine density in the hippocampus. Mutations in the ARHGEF6 gene cause X-linked intellectual disability in humans. Beta-PIX, also called Rho guanine nucleotide exchange factor 7 (ARHGEF7), plays important roles in regulating neuroendocrine exocytosis, focal adhesion maturation, cell migration, synaptic vesicle localization, and insulin secretion. Both alpha-PIX and beta-PIX contain a single copy of the CH domain at the N-terminus. CH domains are actin filament (F-actin) binding motifs.


Pssm-ID: 409051 [Multi-domain]  Cd Length: 114  Bit Score: 41.75  E-value: 2.40e-04
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gi 1946280069   19 KECVEWLTRCDVLRRDHKTNWPEASVIdLANTLRDGVLLCNLLNVLDPGCIDlkDVNQKPQlAQFLCLRNIKTFLQTCHD 98
Cdd:cd21202      3 EQIVTWLISLGLLESPKKETIEDPERF-LSESLKNGVVLCRLVNRLKPGTVE--KIYDEPT-TEEECLYNFESFLKACQE 78

                           90       100       110
                   ....*....|....*....|....*....|...
gi 1946280069   99 IfGLKENDLFEPSMLFELNDFFKVLNTLSKLSN 131
Cdd:cd21202     79 L-GILAEEIFDPNDLYSGGNFQKVLSTLERLEK 110
SH3_AHI-1 cd11812
Src Homology 3 domain of Abelson helper integration site-1 (AHI-1); AHI-1, also called ...
 940-990 2.49e-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: 39.80  E-value: 2.49e-04
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gi 1946280069  940 IAEFDFNPSESNQLPLRKGCQVIVLSKEGDykGWWKGK-VQDRVGFFPKDYV 990
Cdd:cd11812      3 VALYDYTANRSDELTIHRGDIIRVLYKDND--NWWFGSlVNGQQGYFPANYV 52
PH1_FDG_family cd13328
FYVE, RhoGEF and PH domain containing/faciogenital dysplasia family proteins, N-terminal ...
 605-685 2.54e-04

FYVE, RhoGEF and PH domain containing/faciogenital dysplasia family proteins, N-terminal Pleckstrin homology (PH) domain; In general, FGDs have a RhoGEF (DH) domain, followed by an N-terminal PH domain, a FYVE domain and a C-terminal PH domain. All FGDs are guanine nucleotide exchange factors that activates the Rho GTPase Cdc42, an important regulator of membrane trafficking. The RhoGEF domain is responsible for GEF catalytic activity, while the N-terminal PH domain is involved in intracellular targeting of the DH domain. Mutations in the FGD1 gene are responsible for the X-linked disorder known as faciogenital dysplasia (FGDY). PH domains have diverse functions, but in general are involved in targeting proteins to the appropriate cellular location or in the interaction with a binding partner. They share little sequence conservation, but all have a common fold, which is electrostatically polarized. Less than 10% of PH domains bind phosphoinositide phosphates (PIPs) with high affinity and specificity. PH domains are distinguished from other PIP-binding domains by their specific high-affinity binding to PIPs with two vicinal phosphate groups: PtdIns(3,4)P2, PtdIns(4,5)P2 or PtdIns(3,4,5)P3 which results in targeting some PH domain proteins to the plasma membrane. A few display strong specificity in lipid binding. Any specificity is usually determined by loop regions or insertions in the N-terminus of the domain, which are not conserved across all PH domains. PH domains are found in cellular signaling proteins such as serine/threonine kinase, tyrosine kinases, regulators of G-proteins, endocytotic GTPases, adaptors, as well as cytoskeletal associated molecules and in lipid associated enzymes.


Pssm-ID: 275410  Cd Length: 92  Bit Score: 40.94  E-value: 2.54e-04
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gi 1946280069  605 RYIFVFDQVIIMC---KSLRGETYSYRESLRLQEYKIEDVhtrrtlrTDARWSYQFyLVRKSERTaYTLYARTEDNKRKW 681
Cdd:cd13328     18 RYLFLFNDMLLYCvpkLSLVGQKFSVRNRLDVAGMKVREP-------VNENYPHTF-KISGKERS-LELQASSAEEKDEW 88


                   ....
gi 1946280069  682 MKAI 685
Cdd:cd13328     89 IQAI 92
C1_PIK3R-like_rpt2 cd20830
second protein kinase C conserved region 1 (C1 domain) found in uncharacterized ...
 761-791 2.57e-04

second protein kinase C conserved region 1 (C1 domain) found in uncharacterized phosphatidylinositol 3-kinase regulatory subunit-like proteins; The family includes a group of uncharacterized proteins that show high sequence similarity to vertebrate phosphatidylinositol 3-kinase regulatory subunits (PIK3Rs), which bind to activated (phosphorylated) protein-tyrosine kinases through its SH2 domain and regulate their kinase activity. Unlike typical PIK3Rs, members of this family have two C1 domains. This model corresponds to the second one. The C1 domain is a cysteine-rich zinc binding domain that does not bind DNA nor possess structural similarity to conventional zinc finger domains; it contains two separate Zn(2+)-binding sites.


Pssm-ID: 410380  Cd Length: 52  Bit Score: 39.93  E-value: 2.57e-04
                           10        20        30
                   ....*....|....*....|....*....|.
gi 1946280069  761 TTCHHCSKFLKGIILQGYLCGECSIAVHKQC 791
Cdd:cd20830     12 QWCDKCGKFLFGLVHQGLQCQDCGLVCHRTC 42
CH_alphaPIX cd21265
calponin homology (CH) domain found in alpha-Pak Interactive eXchange factor; Alpha-Pak ...
 22-129 2.64e-04

calponin homology (CH) domain found in alpha-Pak Interactive eXchange factor; Alpha-Pak Interactive eXchange factor (alpha-PIX), also called PAK-interacting exchange factor alpha, Rho guanine nucleotide exchange factor 6 (ARHGEF6), Rac/Cdc42 guanine nucleotide exchange factor 6, or Cool (Cloned out of Library)-2, activates small GTPases by exchanging bound GDP for free GTP. It acts as a GEF for both Cdc42 and Rac1, and is localized in dendritic spines where it regulates spine morphogenesis. It controls dendritic length and spine density in the hippocampus. Mutations in the ARHGEF6 gene cause X-linked intellectual disability in humans. Alpha-PIX contains a single copy of the CH domain at its N-terminus. CH domains are actin filament (F-actin) binding motifs.


Pssm-ID: 409114  Cd Length: 117  Bit Score: 41.73  E-value: 2.64e-04
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gi 1946280069   22 VEWLTRCDVLrrdhktNWPEASVID----LANTLRDGVLLCNLLNVLDPGCIDlkDVNQKPQlAQFLCLRNIKTFLQTCh 97
Cdd:cd21265      8 VTWLISLGVL------NSPKKTISDpeefLKSSLKDGVVLCKLIERLLPGSVE--KYCLEPK-TEADCIGNIKEFLKGC- 77

                           90       100       110
                   ....*....|....*....|....*....|..
gi 1946280069   98 diFGLKEnDLFEPSMLFELNDFFKVLNTLSKL 129
Cdd:cd21265     78 --AALKV-ETFEPDDLYTGENFSKVLSTLLAV 106
SH3_CD2AP_3 cd12056
Third Src Homology 3 domain (SH3C) of CD2-associated protein; CD2AP, also called CMS (Cas ...
 941-990 2.84e-04

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


Pssm-ID: 212989 [Multi-domain]  Cd Length: 57  Bit Score: 39.81  E-value: 2.84e-04
                           10        20        30        40        50
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gi 1946280069  941 AEFDFNPSESNQLPLRKGCQVIVLSKEGDYKGWWKGKVQDRVGFFPKDYV 990
Cdd:cd12056      6 ALFHYEGTNEDELDFKEGEIILIISKDTGEPGWWKGELNGKEGVFPDNFV 55
PH_Dbs cd01227
DBL's big sister protein pleckstrin homology (PH) domain; Dbs (also called MCF2-transforming ...
 580-689 3.70e-04

DBL's big sister protein pleckstrin homology (PH) domain; Dbs (also called MCF2-transforming sequence-like protein 2) is a guanine nucleotide exchange factor (GEF), which contains spectrin repeats, a rhoGEF (DH) domain and a PH domain. The Dbs PH domain participates in binding to both the Cdc42 and RhoA GTPases. PH domains have diverse functions, but in general are involved in targeting proteins to the appropriate cellular location or in the interaction with a binding partner. They share little sequence conservation, but all have a common fold, which is electrostatically polarized. Less than 10% of PH domains bind phosphoinositide phosphates (PIPs) with high affinity and specificity. PH domains are distinguished from other PIP-binding domains by their specific high-affinity binding to PIPs with two vicinal phosphate groups: PtdIns(3,4)P2, PtdIns(4,5)P2 or PtdIns(3,4,5)P3 which results in targeting some PH domain proteins to the plasma membrane. A few display strong specificity in lipid binding. Any specificity is usually determined by loop regions or insertions in the N-terminus of the domain, which are not conserved across all PH domains. PH domains are found in cellular signaling proteins such as serine/threonine kinase, tyrosine kinases, regulators of G-proteins, endocytotic GTPases, adaptors, as well as cytoskeletal associated molecules and in lipid associated enzymes.


Pssm-ID: 269934 [Multi-domain]  Cd Length: 126  Bit Score: 41.41  E-value: 3.70e-04
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1946280069  580 LKDYGRLLKDGELKI-----KAHD----DQKIKTRYIFVFDQVIIMCKSlRGE-----TYSYRESLRLQEYKIEDvhtrr 645
Cdd:cd01227      9 LGDLGKLLMQGSFNVwtehkKGHTkklaRFKPMQRHIFLYEKAVLFCKK-RGEngeapSYSYKNSLNTTAVGLTE----- 82

                           90       100       110       120
                   ....*....|....*....|....*....|....*....|....
gi 1946280069  646 TLRTDARwSYQFYLVRKSErtAYTLYARTEDNKRKWMKAIHDAM 689
Cdd:cd01227     83 NVKGDTK-KFEIWLNGREE--VFIIQAPTPEIKAAWVKAIRQVL 123
PH1_FGD3 cd13387
FYVE, RhoGEF and PH domain containing/faciogenital dysplasia protein 3, N-terminal Pleckstrin ...
 586-685 4.23e-04

FYVE, RhoGEF and PH domain containing/faciogenital dysplasia protein 3, N-terminal Pleckstrin homology (PH) domain; In general, FGDs have a RhoGEF (DH) domain, followed by an N-terminal PH domain, a FYVE domain and a C-terminal PH domain. All FGDs are guanine nucleotide exchange factors that activates the Rho GTPase Cdc42, an important regulator of membrane trafficking. The RhoGEF domain is responsible for GEF catalytic activity, while the N-terminal PH domain is involved in intracellular targeting of the DH domain. Both FGD1 and FGD3 are targeted by the ubiquitin ligase SCF(FWD1/beta-TrCP) upon phosphorylation of two serine residues in its DSGIDS motif and subsequently degraded by the proteasome. However, FGD1 and FGD3 induced significantly different morphological changes in HeLa Tet-Off cells and while FGD1 induced long finger-like protrusions, FGD3 induced broad sheet-like protrusions when the level of GTP-bound Cdc42 was significantly increased by the inducible expression of FGD3. They also reciprocally regulated cell motility in inducibly expressed in HeLa Tet-Off cells, FGD1 stimulated cell migration while FGD3 inhibited it. FGD1 and FGD3 therefore play different roles to regulate cellular functions, even though their intracellular levels are tightly controlled by the same destruction pathway through SCF(FWD1/beta-TrCP). PH domains have diverse functions, but in general are involved in targeting proteins to the appropriate cellular location or in the interaction with a binding partner. They share little sequence conservation, but all have a common fold, which is electrostatically polarized. Less than 10% of PH domains bind phosphoinositide phosphates (PIPs) with high affinity and specificity. PH domains are distinguished from other PIP-binding domains by their specific high-affinity binding to PIPs with two vicinal phosphate groups: PtdIns(3,4)P2, PtdIns(4,5)P2 or PtdIns(3,4,5)P3 which results in targeting some PH domain proteins to the plasma membrane. A few display strong specificity in lipid binding. Any specificity is usually determined by loop regions or insertions in the N-terminus of the domain, which are not conserved across all PH domains. PH domains are found in cellular signaling proteins such as serine/threonine kinase, tyrosine kinases, regulators of G-proteins, endocytotic GTPases, adaptors, as well as cytoskeletal associated molecules and in lipid associated enzymes.


Pssm-ID: 275422  Cd Length: 108  Bit Score: 41.11  E-value: 4.23e-04
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1946280069  586 LLKDGELKIKAHDDQKIKTRYIFVFDQVIIMCK---SLRGETYSYRESLRLQEYKIEDVHTRRTLRTdarwsyqFYLVRK 662
Cdd:cd13387      1 LIKEGHIQKLSAKNGTAQDRYLYLFNSMVLYCVpklRLMGQKFSVREKIDIAGMQVQEIVKQNVPHT-------FTITGK 73

                           90       100
                   ....*....|....*....|...
gi 1946280069  663 seRTAYTLYARTEDNKRKWMKAI 685
Cdd:cd13387     74 --KRSLELQARTEEEKKEWIQVI 94
SH3_Eve1_4 cd11817
Fourth Src homology 3 domain of ADAM-binding protein Eve-1; Eve-1, also called SH3 ...
 939-989 4.46e-04

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


Pssm-ID: 212751 [Multi-domain]  Cd Length: 50  Bit Score: 39.00  E-value: 4.46e-04
                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|.
gi 1946280069  939 AIAEFDFNPSESNQLPLRKGCQVIVLSKEGDykGWWKGKVQDRVGFFPKDY 989
Cdd:cd11817      2 AVALYDFTGETEEDLSFQRGDRILVTEHLDA--EWSRGRLNGREGIFPRAF 50
SH2_Tec_Bmx cd10399
Src homology 2 (SH2) domain found in Tec protein, Bmx; A member of the Tec protein tyrosine ...
 825-920 4.55e-04

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


Pssm-ID: 198262  Cd Length: 106  Bit Score: 40.71  E-value: 4.55e-04
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1946280069  825 SLKDHLWFVGEMGRDRASALL-ERHMDGTYLLRVRPQGATHpneTIYALSLKTDDR---VKHMKVYERTMEgvpHYFLSE 900
Cdd:cd10399      2 NLDAYDWFAGNISRSQSEQLLrQKGKEGAFMVRNSSQVGMY---TVSLFSKAVNDKkgtVKHYHVHTNAEN---KLYLAE 75

                           90       100
                   ....*....|....*....|
gi 1946280069  901 SRFFRSITDLIGCYEHSSLG 920
Cdd:cd10399     76 NYCFDSIPKLIHYHQHNSAG 95
SH3_Abi2 cd11972
Src homology 3 domain of Abl Interactor 2; Abi2 is highly expressed in the brain and eye. It ...
 934-996 4.75e-04

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


Pssm-ID: 212905 [Multi-domain]  Cd Length: 61  Bit Score: 39.22  E-value: 4.75e-04
                           10        20        30        40        50        60
                   ....*....|....*....|....*....|....*....|....*....|....*....|...
gi 1946280069  934 FRRIIAIaeFDFNPSESNQLPLRKGCQVIVLSKEGDykGWWKGKVQDRVGFFPKDYVRETLGY 996
Cdd:cd11972      2 LEKVVAI--YDYTKDKEDELSFQEGAIIYVIKKNDD--GWYEGVMNGVTGLFPGNYVESIMHY 60
SH3_Vinexin_1 cd11921
First Src Homology 3 domain of Vinexin, also called Sorbin and SH3 domain containing 3 (Sorbs3) ...
 939-990 4.78e-04

First Src Homology 3 domain of Vinexin, also called Sorbin and SH3 domain containing 3 (Sorbs3); Vinexin is also called Sorbs3, SH3P3, and SH3-containing adapter molecule 1 (SCAM-1). It is an adaptor protein containing one sorbin homology (SoHo) and three SH3 domains. Vinexin was first identified as a vinculin binding protein; it is co-localized with vinculin at cell-ECM and cell-cell adhesion sites. There are several splice variants of vinexin: alpha, which contains the SoHo and three SH3 domains and displays tissue-specific expression; and beta, which contains only the three SH3 domains and is widely expressed. Vinexin alpha stimulates the accumulation of F-actin at focal contact sites. Vinexin also promotes keratinocyte migration and wound healing. The SH3 domains of vinexin have been reported to bind a number of ligands including vinculin, WAVE2, DLG5, Abl, and Cbl. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 212854  Cd Length: 55  Bit Score: 39.14  E-value: 4.78e-04
                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|..
gi 1946280069  939 AIAEFDFNPSESNQLPLRKGcQVIVLSKEGDyKGWWKGKVQDRVGFFPKDYV 990
Cdd:cd11921      3 ARLKFDFQAQSPKELTLQKG-DIVYIHKEVD-KNWLEGEHHGRVGIFPANYV 52
PH1_FGD1-4_like cd13388
FYVE, RhoGEF and PH domain containing/faciogenital dysplasia proteins 1-4 and similar proteins, ...
 586-685 4.96e-04

FYVE, RhoGEF and PH domain containing/faciogenital dysplasia proteins 1-4 and similar proteins, N-terminal Pleckstrin homology (PH) domain; In general, FGDs have a RhoGEF (DH) domain, followed by an N-terminal PH domain, a FYVE domain and a C-terminal PH domain. All FGDs are guanine nucleotide exchange factors that activates the Rho GTPase Cdc42, an important regulator of membrane trafficking. The RhoGEF domain is responsible for GEF catalytic activity, while the N-terminal PH domain is involved in intracellular targeting of the DH domain. Mutations in the FGD1 gene are responsible for the X-linked disorder known as faciogenital dysplasia (FGDY). Both FGD1 and FGD3 are targeted by the ubiquitin ligase SCF(FWD1/beta-TrCP) upon phosphorylation of two serine residues in its DSGIDS motif and subsequently degraded by the proteasome. They play different roles to regulate cellular functions, even though their intracellular levels are tightly controlled by the same destruction pathway. FGD4 is one of the genes associated with Charcot-Marie-Tooth neuropathy type 4 (CMT4), a group of progressive motor and sensory axonal and demyelinating neuropathies that are distinguished from other forms of CMT by autosomal recessive inheritance. Those affected have distal muscle weakness and atrophy associated with sensory loss and, frequently, pes cavus foot deformity. PH domains have diverse functions, but in general are involved in targeting proteins to the appropriate cellular location or in the interaction with a binding partner. They share little sequence conservation, but all have a common fold, which is electrostatically polarized. Less than 10% of PH domains bind phosphoinositide phosphates (PIPs) with high affinity and specificity. PH domains are distinguished from other PIP-binding domains by their specific high-affinity binding to PIPs with two vicinal phosphate groups: PtdIns(3,4)P2, PtdIns(4,5)P2 or PtdIns(3,4,5)P3 which results in targeting some PH domain proteins to the plasma membrane. A few display strong specificity in lipid binding. Any specificity is usually determined by loop regions or insertions in the N-terminus of the domain, which are not conserved across all PH domains. PH domains are found in cellular signaling proteins such as serine/threonine kinase, tyrosine kinases, regulators of G-proteins, endocytotic GTPases, adaptors, as well as cytoskeletal associated molecules and in lipid associated enzymes.


Pssm-ID: 275423  Cd Length: 94  Bit Score: 40.39  E-value: 4.96e-04
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1946280069  586 LLKDGE-LKIKAHDDqKIKTRYIFVFDQVIIMC---KSLRGETYSYRESLRLQEYKIEDVHTRRTLRTdarwsyqFYlVR 661
Cdd:cd13388      1 LIKEGKiLKISARNG-DTQERYLFLFNDMLLYCsprLRLIGQKYKVRARFDVDGMQVLEGDNLETPHT-------FY-VR 71

                           90       100
                   ....*....|....*....|....
gi 1946280069  662 KSERTAyTLYARTEDNKRKWMKAI 685
Cdd:cd13388     72 GKQRSL-ELQASTQEEKAEWVDAI 94
C1_PKD3_rpt2 cd20844
second protein kinase C conserved region 1 (C1 domain) found in protein kinase D3 (PKD3) and ...
 757-791 5.08e-04

second protein kinase C conserved region 1 (C1 domain) found in protein kinase D3 (PKD3) and similar proteins; PKD3 is also called PRKD3, PRKCN, serine/threonine-protein kinase D3 (nPKC-D3), protein kinase C nu type (nPKC-nu), or protein kinase EPK2. It converts transient diacylglycerol (DAG) signals into prolonged physiological effects, downstream of PKC. It is involved in the regulation of the cell cycle by modulating microtubule nucleation and dynamics. PKD3 acts as a key mediator in several cancer development signaling pathways. PKD3 contains N-terminal tandem cysteine-rich zinc binding C1 (PKC conserved region 1), central PH (Pleckstrin Homology), and C-terminal catalytic kinase domains. This model corresponds to the second C1 domain. The C1 domain is a cysteine-rich zinc binding domain that does not bind DNA nor possess structural similarity to conventional zinc finger domains; it contains two separate Zn(2+)-binding sites.


Pssm-ID: 410394  Cd Length: 69  Bit Score: 39.61  E-value: 5.08e-04
                           10        20        30
                   ....*....|....*....|....*....|....*
gi 1946280069  757 YLQATTCHHCSKFLKGIILQGYLCGECSIAVHKQC 791
Cdd:cd20844     13 YTRPTICQYCKRLLKGLFRQGMQCKDCRFNCHKRC 47
C1_alphaCHN cd20856
protein kinase C conserved region 1 (C1 domain) found in alpha-chimaerin and similar proteins; ...
 763-791 5.32e-04

protein kinase C conserved region 1 (C1 domain) found in alpha-chimaerin and similar proteins; Alpha-chimaerin, also called A-chimaerin, N-chimaerin (CHN), alpha-chimerin, N-chimerin (NC), or Rho GTPase-activating protein 2 (ARHGAP2), is a GTPase-activating protein (GAP) for p21-rac and a phorbol ester receptor. It is involved in the assembly of neuronal locomotor circuits as a direct effector of EPHA4 in axon guidance. Alpha-chimaerin contains a functional SH2 domain that can bind to phosphotyrosine motifs within receptors, a GAP domain with specificity in vitro for Rac1 and a diacylglycerol (DAG)-binding C1 domain which allows them to translocate to membranes in response to DAG signaling and anchors them in close proximity to activated Rac. This model corresponds to the C1 domain. The C1 domain is a cysteine-rich zinc binding domain that does not bind DNA nor possess structural similarity to conventional zinc finger domains; it contains two separate Zn(2+)-binding sites.


Pssm-ID: 410406  Cd Length: 57  Bit Score: 39.28  E-value: 5.32e-04
                           10        20
                   ....*....|....*....|....*....
gi 1946280069  763 CHHCSKFLKGIILQGYLCGECSIAVHKQC 791
Cdd:cd20856     19 CEYCANFMWGLIAQGVKCADCGLNVHKQC 47
SH3_CSK cd11769
Src Homology 3 domain of C-terminal Src kinase; CSK is a cytoplasmic (or nonreceptor) tyr ...
 940-992 5.60e-04

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: 38.82  E-value: 5.60e-04
                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....
gi 1946280069  940 IAEFDFNPSESNQLPLRKGCQVIVLSKEGDyKGWWKGKVQD-RVGFFPKDYVRE 992
Cdd:cd11769      5 IAKYNFNGASEEDLPFKKGDILTIVAVTKD-PNWYKAKNKDgREGMIPANYVQK 57
SH2_Fps_family cd10361
Src homology 2 (SH2) domain found in feline sarcoma, Fujinami poultry sarcoma, and fes-related ...
 824-919 5.64e-04

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


Pssm-ID: 198224  Cd Length: 90  Bit Score: 39.82  E-value: 5.64e-04
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1946280069  824 PSLKDHLWFVGEMGRDRASALLERhmDGTYLLRvrpqgATHPNETI---YALSLKTDDRVKHMKVyeRTMEGVPHYFlsE 900
Cdd:cd10361      1 KDLENEPYYHGLLPREDAEELLKN--DGDFLVR-----KTEPKGGGkrkLVLSVRWDGKIRHFVI--NRDDGGKYYI--E 69

                           90
                   ....*....|....*....
gi 1946280069  901 SRFFRSITDLIGCYEHSSL 919
Cdd:cd10361     70 GKSFKSISELINYYQKTKE 88
C1_betaCHN cd20857
protein kinase C conserved region 1 (C1 domain) found in beta-chimaerin and similar proteins; ...
 763-791 6.01e-04

protein kinase C conserved region 1 (C1 domain) found in beta-chimaerin and similar proteins; Beta-chimaerin, also called beta-chimerin (BCH) or Rho GTPase-activating protein 3 (ARHGAP3), is a GTPase-activating protein (GAP) for p21-rac. Insufficient expression of beta-2 chimaerin is expected to lead to higher Rac activity and could therefore play a role in the progression from low-grade to high-grade tumors. Beta-chimaerin contains a functional SH2 domain that can bind to phosphotyrosine motifs within receptors, a GAP domain with specificity in vitro for Rac1 and a diacylglycerol (DAG)-binding C1 domain which allows them to translocate to membranes in response to DAG signaling and anchors them in close proximity to activated Rac. This model corresponds to the C1 domain. The C1 domain is a cysteine-rich zinc binding domain that does not bind DNA nor possess structural similarity to conventional zinc finger domains; it contains two separate Zn(2+)-binding sites.


Pssm-ID: 410407  Cd Length: 61  Bit Score: 39.25  E-value: 6.01e-04
                           10        20
                   ....*....|....*....|....*....
gi 1946280069  763 CHHCSKFLKGIILQGYLCGECSIAVHKQC 791
Cdd:cd20857     19 CEYCANFMWGLIAQGVRCSDCGLNVHKQC 47
C1_AKAP13 cd20878
protein kinase C conserved region 1 (C1 domain) found in A-kinase anchor protein 13 (AKAP-13) ...
 759-793 6.50e-04

protein kinase C conserved region 1 (C1 domain) found in A-kinase anchor protein 13 (AKAP-13) and similar proteins; AKAP-13, also called AKAP-Lbc, breast cancer nuclear receptor-binding auxiliary protein (Brx-1), guanine nucleotide exchange factor Lbc, human thyroid-anchoring protein 31, lymphoid blast crisis oncogene (LBC oncogene), non-oncogenic Rho GTPase-specific GTP exchange factor, protein kinase A-anchoring protein 13 (PRKA13), or p47, is a scaffold protein that plays an important role in assembling signaling complexes downstream of several types of G protein-coupled receptors (GPCRs). It activates RhoA in response to GPCR signaling via its function as a Rho guanine nucleotide exchange factor. It may also activate other Rho family members. AKAP-13 plays a role in cell growth, cell development and actin fiber formation. Its Rho-GEF activity is regulated by protein kinase A (PKA), through binding and phosphorylation. Alternative splicing of this gene in humans has at least 3 transcript variants encoding different isoforms (i.e. proto-/onco-Lymphoid blast crisis, Lbc and breast cancer nuclear receptor-binding auxiliary protein, and Brx) that contain a C1 domain followed by a dbl oncogene homology (DH) domain and a PH domain which are required for full transforming activity. This model corresponds to the C1 domain. The C1 domain is a cysteine-rich zinc binding domain that does not bind DNA nor possess structural similarity to conventional zinc finger domains; it contains two separate Zn(2+)-binding sites.


Pssm-ID: 410428  Cd Length: 60  Bit Score: 38.86  E-value: 6.50e-04
                           10        20        30
                   ....*....|....*....|....*....|....*
gi 1946280069  759 QATTCHHCSKFLKgiILQGYLCGECSIAVHKQCIE 793
Cdd:cd20878     17 GPTQCYHCSKPLN--TKDAFLCANCNVQVHKGCRE 49
SH3_ASPP2 cd11953
Src Homology 3 (SH3) domain of Apoptosis Stimulating of p53 protein 2; ASPP2 is the full ...
 941-988 6.62e-04

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


Pssm-ID: 212886 [Multi-domain]  Cd Length: 57  Bit Score: 38.78  E-value: 6.62e-04
                           10        20        30        40
                   ....*....|....*....|....*....|....*....|....*....
gi 1946280069  941 AEFDFNPSESNQLPLRKG-CQVIVLSKEGDYKGWWKGKVQDRVGFFPKD 988
Cdd:cd11953      5 ALWDYEGESDDELSFKEGdCMTILRREDEDETEWWWARLNDKEGYVPRN 53
CH_LMO7-like cd21208
calponin homology (CH) domain found in LIM domain only protein 7 and similar proteins; This ...
 51-143 7.20e-04

calponin homology (CH) domain found in LIM domain only protein 7 and similar proteins; This family includes LIM domain only protein 7 (LMO-7) and LIM and calponin homology domains-containing protein 1 (LIMCH1), and similar proteins. LMO-7, also called F-box only protein 20, or LOMP, is a transcription regulator for expression of many Emery-Dreifuss muscular dystrophy (EDMD)-relevant genes. It binds to alpha-actinin and AF6/afadin at adherens junctions for epithelial cell-cell adhesion. LIMCH1 acts as an actin stress fiber-associated protein that activates the non-muscle myosin IIa complex by promoting the phosphorylation of its regulatory subunit MRLC/MYL9. It positively regulates actin stress fiber assembly and stabilizes focal adhesions, and therefore negatively regulates cell spreading and cell migration. Members of this family contain a single copy of the CH domain at the N-terminus. CH domains are actin filament (F-actin) binding motifs.


Pssm-ID: 409057 [Multi-domain]  Cd Length: 119  Bit Score: 40.40  E-value: 7.20e-04
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1946280069   51 LRDGVLLCNLLNVLDPGCIdlKDVNQKPqlAQFLCLRNIKTFLQTCHDIfGLKENDLFEPSMLFELNDffKVLNTLSKLS 130
Cdd:cd21208     26 LEDGILLCELINAIKPGSI--KKINRLP--TPIAGLDNLNLFLKACEDL-GLKDSQLFDPTDLQDLSN--RRIATHVRKK 98

                           90
                   ....*....|...
gi 1946280069  131 NCVKVQRKQIIYL 143
Cdd:cd21208     99 EDERRLKNVAITL 111
SH2_N-SH2_Zap70_Syk_like cd09938
N-terminal Src homology 2 (SH2) domain found in Zeta-chain-associated protein kinase 70 ...
 831-936 7.36e-04

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


Pssm-ID: 198191  Cd Length: 104  Bit Score: 40.07  E-value: 7.36e-04
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1946280069  831 WFVGEMGRDRASALLERH--MDGTYLLR--VRPQGAthpnetiYALSLKTDDRVKHMKVyERTMEGVphYFLSESRFFRS 906
Cdd:cd09938      3 FFYGSITREEAEEYLKLAgmSDGLFLLRqsLRSLGG-------YVLSVCHGRKFHHYTI-ERQLNGT--YAIAGGKAHCG 72

                           90       100       110
                   ....*....|....*....|....*....|
gi 1946280069  907 ITDLigCYEHSslgENFVGLDVTLKWPFRR 936
Cdd:cd09938     73 PAEL--CEYHS---TDLDGLVCLLRKPCNR 97
SH3_SH3RF1_3 cd11926
Third Src Homology 3 domain of SH3 domain containing ring finger 1, an E3 ubiquitin-protein ...
 938-990 7.42e-04

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


Pssm-ID: 212859 [Multi-domain]  Cd Length: 55  Bit Score: 38.80  E-value: 7.42e-04
                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....*
gi 1946280069  938 IAIAEFDFNPSESNQLPLRKGCQVIVLSKEGDykGWWKGKVQ--DRVGFFPKDYV 990
Cdd:cd11926      1 VYVAIYPYTPRKEDELELRKGEMFLVFERCQD--GWFKGTSMhtSKIGVFPGNYV 53
C1_MRCKbeta cd20865
protein kinase C conserved region 1 (C1 domain) found in myotonic dystrophy kinase-related ...
 757-791 7.79e-04

protein kinase C conserved region 1 (C1 domain) found in myotonic dystrophy kinase-related Cdc42-binding kinase beta (MRCK beta) and similar proteins; MRCK beta, also called Cdc42-binding protein kinase beta (Cdc42BP-beta), DMPK-like beta, or myotonic dystrophy protein kinase-like beta, is a serine/threonine-protein kinase expressed ubiquitously in many tissues. MRCK beta is an important downstream effector of Cdc42 and plays a role in the regulation of cytoskeleton reorganization and cell migration. The C1 domain is a cysteine-rich zinc binding domain that does not bind DNA nor possess structural similarity to conventional zinc finger domains; it contains two separate Zn(2+)-binding sites.


Pssm-ID: 410415  Cd Length: 53  Bit Score: 38.43  E-value: 7.79e-04
                           10        20        30
                   ....*....|....*....|....*....|....*
gi 1946280069  757 YLQATTCHHCSKFLKGIILQGYLCGECSIAVHKQC 791
Cdd:cd20865      8 FSSPTQCSHCTSLMVGLVRQGYACEVCSFACHVSC 42
SH3_PLCgamma2 cd11969
Src homology 3 domain of Phospholipase C (PLC) gamma 2; PLCgamma2 is primarily expressed in ...
 941-992 7.89e-04

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


Pssm-ID: 212902  Cd Length: 55  Bit Score: 38.67  E-value: 7.89e-04
                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|...
gi 1946280069  941 AEFDFNPSESNQLPLRKGCQVIVLSKEGDykGWWKGKVQDRVG-FFPKDYVRE 992
Cdd:cd11969      4 ALYDYRAKRSDELSFCKGALIHNVSKETG--GWWKGDYGGKVQhYFPSNYVED 54
C1_DGKtheta_typeV_rpt1 cd20803
first protein kinase C conserved region 1 (C1 domain) found in type V diacylglycerol kinase, ...
 702-735 7.92e-04

first protein kinase C conserved region 1 (C1 domain) found in type V diacylglycerol kinase, DAG kinase theta, and similar proteins; Diacylglycerol (DAG) kinase (EC 2.7.1.107) is a lipid kinase that phosphorylates diacylglycerol to form phosphatidic acid. DAG kinase theta, also called diglyceride kinase theta (DGK-theta), is the only isoform classified as type V; it contains a pleckstrin homology (PH)-like domain and an additional C1 domain, compared to other DGKs. It may regulate the activity of protein kinase C by controlling the balance between the two signaling lipids, diacylglycerol and phosphatidic acid. DAG kinase theta contains three copies of the C1 domain. This model corresponds to the first one. The C1 domain is a cysteine-rich zinc binding domain that does not bind DNA nor possess structural similarity to conventional zinc finger domains; it contains two separate Zn(2+)-binding sites.


Pssm-ID: 410353  Cd Length: 56  Bit Score: 38.44  E-value: 7.92e-04
                           10        20        30
                   ....*....|....*....|....*....|....*..
gi 1946280069  702 HTFKMNTFEQATTCHHCSKFLKGIILQ--VCT-CRYV 735
Cdd:cd20803      2 HSFRKKTFHKPTYCHHCTDLLWGLLNQgyQCEvCNFV 38
C1_PKD_rpt2 cd20796
second protein kinase C conserved region 1 (C1 domain) found in the family of protein kinase D ...
 702-733 8.01e-04

second protein kinase C conserved region 1 (C1 domain) found in the family of protein kinase D (PKD); PKDs are important regulators of many intracellular signaling pathways such as ERK and JNK, and cellular processes including the organization of the trans-Golgi network, membrane trafficking, cell proliferation, migration, and apoptosis. They are activated in a PKC-dependent manner by many agents including diacylglycerol (DAG), PDGF, neuropeptides, oxidative stress, and tumor-promoting phorbol esters, among others. Mammals harbor three types of PKDs: PKD1 (or PKCmu), PKD2, and PKD3 (or PKCnu). PKDs contain N-terminal tandem cysteine-rich zinc binding C1 (PKC conserved region 1), central PH (Pleckstrin Homology), and C-terminal catalytic kinase domains. This model corresponds to the second C1 domain. The C1 domain is a cysteine-rich zinc binding domain that does not bind DNA nor possess structural similarity to conventional zinc finger domains; it contains two separate Zn(2+)-binding sites.


Pssm-ID: 410346  Cd Length: 54  Bit Score: 38.42  E-value: 8.01e-04
                           10        20        30
                   ....*....|....*....|....*....|..
gi 1946280069  702 HTFKMNTFEQATTCHHCSKFLKGIILQVCTCR 733
Cdd:cd20796      2 HTFVVHTYTKPTVCQHCKKLLKGLFRQGLQCK 33
C1_PKD_rpt1 cd20795
first protein kinase C conserved region 1 (C1 domain) found in the protein kinase D (PKD) ...
 757-792 9.68e-04

first protein kinase C conserved region 1 (C1 domain) found in the protein kinase D (PKD) family; PKDs are important regulators of many intracellular signaling pathways such as ERK and JNK, and cellular processes including the organization of the trans-Golgi network, membrane trafficking, cell proliferation, migration, and apoptosis. They are activated in a PKC-dependent manner by many agents including diacylglycerol (DAG), PDGF, neuropeptides, oxidative stress, and tumor-promoting phorbol esters, among others. Mammals harbor three types of PKDs: PKD1 (or PKCmu), PKD2, and PKD3 (or PKCnu). PKDs contain N-terminal tandem cysteine-rich zinc binding C1 (PKC conserved region 1), central PH (Pleckstrin Homology), and C-terminal catalytic kinase domains. This model corresponds to the first C1 domain. The C1 domain is a cysteine-rich zinc binding domain that does not bind DNA nor possess structural similarity to conventional zinc finger domains; it contains two separate Zn(2+)-binding sites.


Pssm-ID: 410345  Cd Length: 56  Bit Score: 38.44  E-value: 9.68e-04
                           10        20        30
                   ....*....|....*....|....*....|....*.
gi 1946280069  757 YLQATTCHHCSKFLKGIILQGYLCGECSIAVHKQCI 792
Cdd:cd20795     11 YKSPTFCDFCGEMLFGLVRQGLKCEGCGLNFHKRCA 46
SH3_CIN85_2 cd12055
Second Src Homology 3 domain (SH3B) of Cbl-interacting protein of 85 kDa; CIN85, also called ...
 941-992 9.97e-04

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


Pssm-ID: 212988 [Multi-domain]  Cd Length: 53  Bit Score: 38.05  E-value: 9.97e-04
                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|..
gi 1946280069  941 AEFDFNPSESNQLPLRKGcQVIVLSKEGDyKGWWKGKVQDRVGFFPKDYVRE 992
Cdd:cd12055      4 VAFSYLPQNEDELELKVG-DIIEVVGEVE-EGWWEGVLNGKTGMFPSNFIKE 53
SH3_OSTF1 cd11772
Src Homology 3 domain of metazoan osteoclast stimulating factor 1; OSTF1, also named OSF or ...
 941-992 1.02e-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: 38.05  E-value: 1.02e-03
                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|..
gi 1946280069  941 AEFDFNPSESNQLPLRKGCQVIVLSKEGDykGWWKGKVQDRVGFFPKDYVRE 992
Cdd:cd11772      4 ALYDYEAQHPDELSFEEGDLLYISDKSDP--NWWKATCGGKTGLIPSNYVEE 53
C1_MRCKalpha cd20864
protein kinase C conserved region 1 (C1 domain) found in myotonic dystrophy kinase-related ...
 701-732 1.15e-03

protein kinase C conserved region 1 (C1 domain) found in myotonic dystrophy kinase-related Cdc42-binding kinase alpha (MRCK alpha) and similar proteins; MRCK alpha, also called Cdc42-binding protein kinase alpha, DMPK-like alpha, or myotonic dystrophy protein kinase-like alpha, is a serine/threonine-protein kinase expressed ubiquitously in many tissues. It plays a role in the regulation of peripheral actin reorganization and neurite outgrowth. It may also play a role in the transferrin iron uptake pathway. MRCK alpha is an important downstream effector of Cdc42 and plays a role in the regulation of cytoskeleton reorganization and cell migration. The C1 domain is a cysteine-rich zinc binding domain that does not bind DNA nor possess structural similarity to conventional zinc finger domains; it contains two separate Zn(2+)-binding sites.


Pssm-ID: 410414  Cd Length: 60  Bit Score: 38.46  E-value: 1.15e-03
                           10        20        30
                   ....*....|....*....|....*....|..
gi 1946280069  701 THTFKMNTFEQATTCHHCSKFLKGIILQVCTC 732
Cdd:cd20864      2 AHQFVVKSFTTPTKCNQCTSLMVGLIRQGCTC 33
SH3_Abi cd11826
Src homology 3 domain of Abl Interactor proteins; Abl interactor (Abi) proteins are adaptor ...
 940-990 1.21e-03

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


Pssm-ID: 212760 [Multi-domain]  Cd Length: 52  Bit Score: 38.07  E-value: 1.21e-03
                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|.
gi 1946280069  940 IAEFDFNPSESNQLPLRKGCQVIVLSKEGDykGWWKGKVQDRVGFFPKDYV 990
Cdd:cd11826      3 VALYDYTADKDDELSFQEGDIIYVTKKNDD--GWYEGVLNGVTGLFPGNYV 51
C1_CeDKF1-like_rpt1 cd20797
first protein kinase C conserved region 1 (C1 domain) found in Caenorhabditis elegans serine ...
 748-793 1.34e-03

first protein kinase C conserved region 1 (C1 domain) found in Caenorhabditis elegans serine/threonine-protein kinase DKF-1 and similar proteins; DKF-1 converts transient diacylglycerol (DAG) signals into prolonged physiological effects, independently of PKC. It plays a role in the regulation of growth and neuromuscular control of movement. It is involved in immune response to Staphylococcus aureus bacterium by activating transcription factor hlh-30 downstream of phospholipase plc-1. Members of this group contain two copies of the C1 domain. This model corresponds to the first one. The C1 domain is a cysteine-rich zinc binding domain that does not bind DNA nor possess structural similarity to conventional zinc finger domains; it contains two separate Zn(2+)-binding sites.


Pssm-ID: 410347  Cd Length: 56  Bit Score: 37.84  E-value: 1.34e-03
                           10        20        30        40
                   ....*....|....*....|....*....|....*....|....*.
gi 1946280069  748 PQGYYTPgmylqaTTCHHCSKFLKGIILQGYLCGECSIAVHKQCIE 793
Cdd:cd20797      8 VEQYMTP------TFCDYCGEMLTGLMKQGVKCKNCRCNFHKRCAN 47
C1_Sbf-like cd20827
protein kinase C conserved region 1 (C1 domain) found in the myotubularin-related protein Sbf ...
 757-793 1.42e-03

protein kinase C conserved region 1 (C1 domain) found in the myotubularin-related protein Sbf and similar proteins; This group includes Drosophila melanogaster SET domain binding factor (Sbf), the single homolog of human MTMR5/MTMR13, and similar proteins, that show high sequence similarity to vertebrate myotubularin-related proteins (MTMRs) which may function as guanine nucleotide exchange factors (GEFs). Sbf is a pseudophosphatase that coordinates both phosphatidylinositol 3-phosphate (PI(3)P) turnover and Rab21 GTPase activation in an endosomal pathway that controls macrophage remodeling. It also functions as a GEF that promotes Rab21 GTPase activation associated with PI(3)P endosomes. Vertebrate MTMR5 and MTMR13 contain an N-terminal DENN domain, a PH-GRAM domain, an inactive PTP domain, a SET interaction domain, a coiled-coil domain, and a C-terminal PH domain. Members of this family contain these domains and have an additional C1 domain. This model corresponds to the C1 domain. The C1 domain is a cysteine-rich zinc binding domain that does not bind DNA nor possess structural similarity to conventional zinc finger domains; it contains two separate Zn(2+)-binding sites.


Pssm-ID: 410377  Cd Length: 53  Bit Score: 37.78  E-value: 1.42e-03
                           10        20        30
                   ....*....|....*....|....*....|....*..
gi 1946280069  757 YLQATTCHHCSKFLKGIILQGYLCGECSIAVHKQCIE 793
Cdd:cd20827      9 FTTPTYCDYCSSLLWGLVKTGMRCADCGYSCHEKCLE 45
SH3_Stac3_1 cd11986
First C-terminal Src homology 3 domain of SH3 and cysteine-rich domain-containing protein 3 ...
 940-990 1.44e-03

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


Pssm-ID: 212919 [Multi-domain]  Cd Length: 53  Bit Score: 37.58  E-value: 1.44e-03
                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|.
gi 1946280069  940 IAEFDFNPSESNQLPLRKGCQVIVLSKEGDYkgWWKGKVQDRVGFFPKDYV 990
Cdd:cd11986      3 VALYRFKALEKDDLDFHPGERITVIDDSNEE--WWRGKIGEKTGYFPMNFI 51
C1_MTMR-like cd20828
protein kinase C conserved region 1 (C1 domain) found in uncharacterized proteins similar to ...
 752-792 1.46e-03

protein kinase C conserved region 1 (C1 domain) found in uncharacterized proteins similar to myotubularin-related proteins; The family includes a group of uncharacterized proteins that show high sequence similarity to vertebrate myotubularin-related proteins (MTMRs), such as MTMR5 and MTMR13. MTMRs may function as guanine nucleotide exchange factors (GEFs). Vertebrate MTMR5 and MTMR13 contain an N-terminal DENN domain, a PH-GRAM domain, an inactive PTP domain, a SET interaction domain, a coiled-coil domain, and a C-terminal PH domain. Members of this family contain these domains and have an additional C1 domain. This model corresponds to the C1 domain. The C1 domain is a cysteine-rich zinc binding domain that does not bind DNA nor possess structural similarity to conventional zinc finger domains; it contains two separate Zn(2+)-binding sites.


Pssm-ID: 410378  Cd Length: 57  Bit Score: 37.81  E-value: 1.46e-03
                           10        20        30        40
                   ....*....|....*....|....*....|....*....|.
gi 1946280069  752 YTPGMYLQATTCHHCSKFLKGIILQGYLCGECSIAVHKQCI 792
Cdd:cd20828      8 FEPHSFVTPTNCDYCLQILWGIVKKGMKCSECGYNCHEKCQ 48
SH3_Sorbs2_1 cd11920
First Src Homology 3 domain of Sorbin and SH3 domain containing 2 (Sorbs2), also called ...
 939-992 1.48e-03

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


Pssm-ID: 212853 [Multi-domain]  Cd Length: 55  Bit Score: 37.68  E-value: 1.48e-03
                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....
gi 1946280069  939 AIAEFDFNPSESNQLPLRKGCQVIVLSKEGdyKGWWKGKVQDRVGFFPKDYVRE 992
Cdd:cd11920      3 ARAVYDFKAQTSKELSFKKGDTVYILRKID--QNWYEGEHHGRVGIFPISYVEK 54
C1_RASGRP cd20808
protein kinase C conserved region 1 (C1 domain) found in the RAS guanyl-releasing protein ...
 702-733 1.48e-03

protein kinase C conserved region 1 (C1 domain) found in the RAS guanyl-releasing protein (RASGRP) family; The RASGRP family includes RASGRP1-4. They function as cation-, usually calcium-, and diacylglycerol (DAG)-regulated nucleotide exchange factor activating Ras through the exchange of bound GDP for GTP. RASGRP1, also called calcium and DAG-regulated guanine nucleotide exchange factor II (CalDAG-GEFII) or Ras guanyl-releasing protein, activates the Erk/MAP kinase cascade and regulates T-cell/B-cell development, homeostasis and differentiation by coupling T-lymphocyte/B-lymphocyte antigen receptors to Ras. RASGRP1 also regulates NK cell cytotoxicity and ITAM-dependent cytokine production by activation of Ras-mediated ERK and JNK pathways. RASGRP2, also called calcium and DAG-regulated guanine nucleotide exchange factor I (CalDAG-GEFI), Cdc25-like protein (CDC25L), or F25B3.3 kinase-like protein, specifically activates Rap and may also activate other GTPases such as RRAS, RRAS2, NRAS, KRAS but not HRAS. RASGRP2 is involved in aggregation of platelets and adhesion of T-lymphocytes and neutrophils probably through inside-out integrin activation, as well as in the muscarinic acetylcholine receptor M1/CHRM1 signaling pathway. RASGRP3, also called calcium and DAG-regulated guanine nucleotide exchange factor III (CalDAG-GEFIII), or guanine nucleotide exchange factor for Rap1, is a guanine nucleotide-exchange factor activating H-Ras, R-Ras and Ras-associated protein-1/2. It functions as an important mediator of signaling downstream from receptor coupled phosphoinositide turnover in B and T cells. RASGRP4 may function in mast cell differentiation. The C1 domain is a cysteine-rich zinc binding domain that does not bind DNA nor possess structural similarity to conventional zinc finger domains; it contains two separate Zn(2+)-binding sites.


Pssm-ID: 410358  Cd Length: 52  Bit Score: 37.70  E-value: 1.48e-03
                           10        20        30
                   ....*....|....*....|....*....|..
gi 1946280069  702 HTFKMNTFEQATTCHHCSKFLKGIILQVCTCR 733
Cdd:cd20808      2 HNFQETTYFKPTFCDHCTGLLWGLIKQGYKCK 33
PH1_FARP1-like cd01220
FERM, RhoGEF and pleckstrin domain-containing protein 1 and related proteins Pleckstrin ...
 605-690 1.52e-03

FERM, RhoGEF and pleckstrin domain-containing protein 1 and related proteins Pleckstrin Homology (PH) domain, repeat 1; Members here include FARP1 (also called Chondrocyte-derived ezrin-like protein; PH domain-containing family C member 2), FARP2 (also called FIR/FERM domain including RhoGEF; FGD1-related Cdc42-GEF/FRG), and FARP6 (also called Zinc finger FYVE domain-containing protein 24). They are members of the Dbl family guanine nucleotide exchange factors (GEFs) which are upstream positive regulators of Rho GTPases. Little is known about FARP1 and FARP6, though FARP1 has increased expression in differentiated chondrocytes. FARP2 is thought to regulate neurite remodeling by mediating the signaling pathways from membrane proteins to Rac. It is found in brain, lung, and testis, as well as embryonic hippocampal and cortical neurons. FARP1 and FARP2 are composed of a N-terminal FERM domain, a proline-rich (PR) domain, Dbl-homology (DH), and two C-terminal PH domains. FARP6 is composed of Dbl-homology (DH), and two C-terminal PH domains separated by a FYVE domain. This hierarchy contains the first PH repeat. PH domains have diverse functions, but in general are involved in targeting proteins to the appropriate cellular location or in the interaction with a binding partner. They share little sequence conservation, but all have a common fold, which is electrostatically polarized. Less than 10% of PH domains bind phosphoinositide phosphates (PIPs) with high affinity and specificity. PH domains are distinguished from other PIP-binding domains by their specific high-affinity binding to PIPs with two vicinal phosphate groups: PtdIns(3,4)P2, PtdIns(4,5)P2 or PtdIns(3,4,5)P3 which results in targeting some PH domain proteins to the plasma membrane. A few display strong specificity in lipid binding. Any specificity is usually determined by loop regions or insertions in the N-terminus of the domain, which are not conserved across all PH domains. PH domains are found in cellular signaling proteins such as serine/threonine kinase, tyrosine kinases, regulators of G-proteins, endocytotic GTPases, adaptors, as well as cytoskeletal associated molecules and in lipid associated enzymes.


Pssm-ID: 269928  Cd Length: 109  Bit Score: 39.22  E-value: 1.52e-03
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gi 1946280069  605 RYIFVFDQVIImckslrgetYSYRESLRLQEYKiedVHTRRTLR------TDARWSYQFYLVRKSERTAYTLYARTEDNK 678
Cdd:cd01220     25 RMFFLFSDVLL---------YTSRSPTPSLQFK---VHGQLPLRglmveeSEPEWGVAHCFTIYGGNRALTVAASSEEEK 92

                           90
                   ....*....|..
gi 1946280069  679 RKWMKAIHDAMD 690
Cdd:cd01220     93 ERWLEDLQRAID 104
SH3_p40phox cd11869
Src Homology 3 domain of the p40phox subunit of NADPH oxidase; p40phox, also called Neutrophil ...
 939-991 1.54e-03

Src Homology 3 domain of the p40phox subunit of NADPH oxidase; p40phox, also called Neutrophil cytosol factor 4 (NCF-4), is a cytosolic subunit of the phagocytic NADPH oxidase complex (also called Nox2 or gp91phox) which plays a crucial role in the cellular response to bacterial infection. NADPH oxidase catalyzes the transfer of electrons from NADPH to oxygen during phagocytosis forming superoxide and reactive oxygen species. p40phox positively regulates NADPH oxidase in both phosphatidylinositol-3-phosphate (PI3P)-dependent and PI3P-independent manner. It contains an N-terminal PX domain, a central SH3 domain, and a C-terminal PB1 domain that interacts with p67phox. The SH3 domain of p40phox binds to canonical polyproline and noncanonical motifs at the C-terminus of p47phox. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 212802  Cd Length: 54  Bit Score: 37.86  E-value: 1.54e-03
                           10        20        30        40        50
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gi 1946280069  939 AIAEFDFNPSESNQLPLRKGCQVIVLSKEGdyKGWWKGKVQDRVGFFPKDYVR 991
Cdd:cd11869      2 AEALFDFTGNSKLELNFKAGDVIFLLSRVN--KDWLEGTVRGATGIFPLSFVK 52
CH_dMP20-like cd21207
calponin homology (CH) domain found in Drosophila melanogaster muscle-specific protein 20 ...
 46-129 1.55e-03

calponin homology (CH) domain found in Drosophila melanogaster muscle-specific protein 20 (dMP20) and similar domains; This subfamily contains Drosophila melanogaster muscle-specific protein 20 (dMP20), Echinococcus granulosus myophilin, Dictyostelium discoideum Rac guanine nucleotide exchange factor B (also called Trix), and similar proteins. dMP20 is present only in the synchronous muscles of D. melanogaster. It may be involved in the system linking the nerve impulse with the contraction or the relaxation process. Trix is involved in the regulation of the late steps of the endocytic pathway. dMP20 contains a single copy of the CH domain, while Trix (triple CH-domain array exchange factor) contains three, two type 3 CH domains which are included in this model, and one type 1 CH domain that is not included in this subfamily, but is part of the superfamily. CH domains are actin filament (F-actin) binding motifs.


Pssm-ID: 409056 [Multi-domain]  Cd Length: 107  Bit Score: 39.22  E-value: 1.55e-03
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gi 1946280069   46 DLANTLRDGVLLCNLLNVLDPGCIdlKDVNQKPQlaQFLCLRNIKTFLQTCHDiFGLKENDLFEPSMLFELNDFFKVLNT 125
Cdd:cd21207     27 DYEDVLKDGVILCKLINILKPGSV--KKINTSKM--AFKLMENIENFLTACKG-YGVPKTDLFQTVDLYEKKNIPQVTNC 101


                   ....
gi 1946280069  126 LSKL 129
Cdd:cd21207    102 LFAL 105
SH3_CRK_N cd11758
N-terminal Src Homology 3 domain of Ct10 Regulator of Kinase adaptor proteins; CRK adaptor ...
 940-992 1.57e-03

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: 37.73  E-value: 1.57e-03
                           10        20        30        40        50
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gi 1946280069  940 IAEFDFNPSESNQLPLRKGCQVIVLSKEGDYkgWWKGKVQD-RVGFFPKDYVRE 992
Cdd:cd11758      4 RALFDFPGNDDEDLPFKKGEILTVIRKPEEQ--WWNARNSEgKTGMIPVPYVEK 55
SH3_FCHSD_2 cd11762
Second Src Homology 3 domain of FCH and double SH3 domains proteins; This group is composed of ...
 941-992 1.63e-03

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


Pssm-ID: 212696 [Multi-domain]  Cd Length: 57  Bit Score: 37.76  E-value: 1.63e-03
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gi 1946280069  941 AEFDFNPSESNQLPLRKGCQVIVLSKE--GDYKGWWKGKVQDRVGFFPKDYVRE 992
Cdd:cd11762      4 ALYDYEAQSDEELSFPEGAIIRILRKDdnGVDDGWWEGEFNGRVGVFPSLVVEE 57
C1_GMIP-like cd20816
protein kinase C conserved region 1 (C1 domain) found in the GEM-interacting protein (GMIP) ...
 759-793 1.64e-03

protein kinase C conserved region 1 (C1 domain) found in the GEM-interacting protein (GMIP)-like family; The GMIP-like family includes GMIP, Rho GTPase-activating protein 29 (ARHGAP29) and Rho GTPase-activating protein 45 (ARHGAP45). GMIP is a RhoA-specific GTPase-activating protein that acts as a key factor in saltatory neuronal migration. It associates with the Rab27a effector JFC1 and modulates vesicular transport and exocytosis. ARHGAP29, also called PTPL1-associated RhoGAP protein 1 (PARG1) or Rho-type GTPase-activating protein 29, is a GTPase activator for the Rho-type GTPases by converting them to an inactive GDP-bound state. It has strong activity toward RHOA, and weaker activity toward RAC1 and CDC42. ARHGAP29 may act as a specific effector of RAP2A to regulate Rho. In concert with RASIP1, ARHGAP29 suppresses RhoA signaling and dampens ROCK and MYH9 activities in endothelial cells and plays an essential role in blood vessel tubulogenesis. ARHGAP45, also called minor histocompatibility antigen HA-1 (mHag HA-1), is a Rac-GAP (GTPase-Activating Protein) in endothelial cells. It acts as a novel regulator of endothelial integrity. ARHGAP45 contains a GTPase activator for the Rho-type GTPases (RhoGAP) domain that would be able to negatively regulate the actin cytoskeleton as well as cell spreading. However, it also contains N-terminally a BAR-domin which can play an autoinhibitory effect on this RhoGAP activity. Members of this family contain a zinc-binding C1 domain. The C1 domain is a cysteine-rich zinc binding domain that does not bind DNA nor possess structural similarity to conventional zinc finger domains; it contains two separate Zn(2+)-binding sites.


Pssm-ID: 410366  Cd Length: 51  Bit Score: 37.62  E-value: 1.64e-03
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gi 1946280069  759 QATTCHHCSKFlkgIILQGYLCGECSIAVHKQCIE 793
Cdd:cd20816     10 TPSKCRECDSY---VYFNGAECEECGLACHKKCLE 41
C1 cd00029
protein kinase C conserved region 1 (C1 domain) superfamily; The C1 domain is a cysteine-rich ...
 702-733 1.76e-03

protein kinase C conserved region 1 (C1 domain) superfamily; The C1 domain is a cysteine-rich zinc binding domain that does not bind DNA nor possess structural similarity to conventional zinc finger domains. It contains the motif HX12CX2CXnCX2CX4HX2CX7C, where C and H are cysteine and histidine, respectively; X represents other residues; and n is either 13 or 14. C1 has a globular fold with two separate Zn(2+)-binding sites. It was originally discovered as lipid-binding modules in protein kinase C (PKC) isoforms. C1 domains that bind and respond to phorbol esters (PE) and diacylglycerol (DAG) are referred to as typical, and those that do not respond to PE and DAG are deemed atypical. A C1 domain may also be referred to as PKC or non-PKC C1, based on the parent protein's activity. Most C1 domain-containing non-PKC proteins act as lipid kinases and scaffolds, except PKD which acts as a protein kinase. PKC C1 domains play roles in membrane translocation and activation of the enzyme.


Pssm-ID: 410341  Cd Length: 50  Bit Score: 37.50  E-value: 1.76e-03
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gi 1946280069  702 HTFKMNTFEQATTCHHCSKFLKGIILQVCTCR 733
Cdd:cd00029      1 HRFVPTTFSSPTFCDVCGKLIWGLFKQGLKCS 32
SH3_Nck_1 cd11765
First Src Homology 3 domain of Nck adaptor proteins; Nck adaptor proteins regulate actin ...
 938-990 1.78e-03

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: 37.40  E-value: 1.78e-03
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gi 1946280069  938 IAIAEFDFNPSESNQLPLRKGCQVIVLSkegDYKGWWK-GKVQDRVGFFPKDYV 990
Cdd:cd11765      1 YVVAKYDYTAQGDQELSIKKNEKLTLLD---DSKHWWKvQNSSNQTGYVPSNYV 51
SH3_MYO15 cd11884
Src Homology 3 domain of Myosin XV; This subfamily is composed of proteins with similarity to ...
 939-990 1.93e-03

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


Pssm-ID: 212817 [Multi-domain]  Cd Length: 56  Bit Score: 37.31  E-value: 1.93e-03
                           10        20        30        40        50
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gi 1946280069  939 AIAEFDFNPSESNQLPLRKGCQVIVLSKEGDYK-GWWKGKVQDRVGFFPKDYV 990
Cdd:cd11884      2 VVAVRAYITRDQTLLSFHKGDVIKLLPKEGPLDpGWLFGTLDGRSGAFPKEYV 54
C1_dGM13116p-like cd20831
protein kinase C conserved region 1 (C1 domain) found in Drosophila melanogaster GM13116p and ...
 761-791 2.03e-03

protein kinase C conserved region 1 (C1 domain) found in Drosophila melanogaster GM13116p and similar proteins; This group contains uncharacterized proteins including Drosophila melanogaster GM13116p and Caenorhabditis elegans hypothetical protein R11G1.4, both of which contain C2 (a calcium-binding domain) and C1 domains. This model describes the C1 domain, a cysteine-rich zinc binding domain that does not bind DNA nor possess structural similarity to conventional zinc finger domains; it contains two separate Zn(2+)-binding sites.


Pssm-ID: 410381  Cd Length: 58  Bit Score: 37.32  E-value: 2.03e-03
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gi 1946280069  761 TTCHHCSKFLKGII-LQGYLCGECSIAVHKQC 791
Cdd:cd20831     17 PSCAVCNKLIPGRFgKQGYQCRDCGLICHKRC 48
SH3_SH3RF_1 cd11786
First Src Homology 3 domain of SH3 domain containing ring finger proteins; This model ...
 939-990 2.35e-03

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


Pssm-ID: 212720 [Multi-domain]  Cd Length: 53  Bit Score: 36.96  E-value: 2.35e-03
                           10        20        30        40        50
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gi 1946280069  939 AIAEFDFNPSESNQLPLRKGcQVIVLSKEGDyKGWWKGKVQDRVGFFPKDYV 990
Cdd:cd11786      2 AKALYNYEGKEPGDLSFKKG-DIILLRKRID-ENWYHGECNGKQGFFPASYV 51
SH3_MIA_like cd11760
Src Homology 3 domain of Melanoma Inhibitory Activity protein and similar proteins; MIA is a ...
 939-992 2.39e-03

Src Homology 3 domain of Melanoma Inhibitory Activity protein and similar proteins; MIA is a single domain protein that adopts a SH3 domain-like fold; it contains an additional antiparallel beta sheet and two disulfide bonds compared to classical SH3 domains. MIA is secreted from malignant melanoma cells and it plays an important role in melanoma development and invasion. MIA is expressed by chondrocytes in normal tissues and may be important in the cartilage cell phenotype. Unlike classical SH3 domains, MIA does not bind proline-rich ligands. MIA is a member of the recently identified family that also includes MIA-like (MIAL), MIA2, and MIA3 (also called TANGO); the biological functions of this family are not yet fully understood.


Pssm-ID: 212694  Cd Length: 76  Bit Score: 37.85  E-value: 2.39e-03
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gi 1946280069  939 AIAEFDFNPSESNQLPLRKGCQVIVLSK-EGDYKGWWKGKVQD---RVGFFPKDYVRE 992
Cdd:cd11760     14 ARALEDYHGPDCRFLNFKKGDTIYVYSKlAGERQDLWAGSVGGdagLFGYFPKNLVQE 71
SH3_srGAP4 cd11956
Src homology 3 domain of Slit-Robo GTPase Activating Protein 4; srGAP4, also called ARHGAP4, ...
 939-990 2.50e-03

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


Pssm-ID: 212889 [Multi-domain]  Cd Length: 55  Bit Score: 37.13  E-value: 2.50e-03
                           10        20        30        40        50
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gi 1946280069  939 AIAEFDFNPSESNQLPLRKGCQVIVLSK-EGDykgWWKGKVQDRVGFFPKDYV 990
Cdd:cd11956      4 AVACFDYTGRTAQELSFKRGDVLLLHSKaSSD---WWRGEHNGMRGLIPHKYI 53
PH1_FGD1 cd01219
FYVE, RhoGEF and PH domain containing/faciogenital dysplasia protein 1, N-terminal Pleckstrin ...
 586-696 3.35e-03

FYVE, RhoGEF and PH domain containing/faciogenital dysplasia protein 1, N-terminal Pleckstrin homology (PH) domain; In general, FGDs have a RhoGEF (DH) domain, followed by an N-terminal PH domain, a FYVE domain and a C-terminal PH domain. All FGDs are guanine nucleotide exchange factors that activates the Rho GTPase Cdc42, an important regulator of membrane trafficking. The RhoGEF domain is responsible for GEF catalytic activity, while the N-terminal PH domain is involved in intracellular targeting of the DH domain. Mutations in the FGD1 gene are responsible for the X-linked disorder known as faciogenital dysplasia (FGDY). Both FGD1 and FGD3 are targeted by the ubiquitin ligase SCF(FWD1/beta-TrCP) upon phosphorylation of two serine residues in its DSGIDS motif and subsequently degraded by the proteasome. However, FGD1 and FGD3 induced significantly different morphological changes in HeLa Tet-Off cells and while FGD1 induced long finger-like protrusions, FGD3 induced broad sheet-like protrusions when the level of GTP-bound Cdc42 was significantly increased by the inducible expression of FGD3. They also reciprocally regulated cell motility in inducibly expressed in HeLa Tet-Off cells, FGD1 stimulated cell migration while FGD3 inhibited it. FGD1 and FGD3 therefore play different roles to regulate cellular functions, even though their intracellular levels are tightly controlled by the same destruction pathway through SCF(FWD1/beta-TrCP). PH domains have diverse functions, but in general are involved in targeting proteins to the appropriate cellular location or in the interaction with a binding partner. They share little sequence conservation, but all have a common fold, which is electrostatically polarized. Less than 10% of PH domains bind phosphoinositide phosphates (PIPs) with high affinity and specificity. PH domains are distinguished from other PIP-binding domains by their specific high-affinity binding to PIPs with two vicinal phosphate groups: PtdIns(3,4)P2, PtdIns(4,5)P2 or PtdIns(3,4,5)P3 which results in targeting some PH domain proteins to the plasma membrane. A few display strong specificity in lipid binding. Any specificity is usually determined by loop regions or insertions in the N-terminus of the domain, which are not conserved across all PH domains. PH domains are found in cellular signaling proteins such as serine/threonine kinase, tyrosine kinases, regulators of G-proteins, endocytotic GTPases, adaptors, as well as cytoskeletal associated molecules and in lipid associated enzymes.


Pssm-ID: 275392  Cd Length: 108  Bit Score: 38.46  E-value: 3.35e-03
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gi 1946280069  586 LLKDGE-LKIKAHDDQKiKTRYIFVFDQVIIMC-KSLR--GETYSYRESLRLQEYKIEDVHTRRTLRTdarwsyqfYLVR 661
Cdd:cd01219      1 LIKEGHiLKLSAKNGTT-QDRYLILFNDRLLYCvPKLRliGQKFSVRARIDVEGMELKESSSLNLPRT--------FLVS 71

                           90       100       110
                   ....*....|....*....|....*....|....*
gi 1946280069  662 KSERTaYTLYARTEDNKRKWMKAIHDAMDNLEPSV 696
Cdd:cd01219     72 GKQRS-LELQARTEEEKKDWIQAIQATIQRHEQTL 105
SH3_srGAP1-3 cd11955
Src homology 3 domain of Slit-Robo GTPase Activating Proteins 1, 2, and 3; srGAP1, also called ...
 939-990 3.95e-03

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


Pssm-ID: 212888 [Multi-domain]  Cd Length: 53  Bit Score: 36.46  E-value: 3.95e-03
                           10        20        30        40        50
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gi 1946280069  939 AIAEFDFNPSESNQLPLRKGCQVIVLSKEGDykGWWKGKVQDRVGFFPKDYV 990
Cdd:cd11955      2 AIAKFDYVGRSARELSFKKGASLLLYHRASD--DWWEGRHNGIDGLVPHQYI 51
SH3_PEX13_eumet cd11864
Src Homology 3 domain of eumetazoan Peroxisomal biogenesis factor 13; PEX13 is a peroxin and ...
 938-991 4.08e-03

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: 36.45  E-value: 4.08e-03
                           10        20        30        40        50
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gi 1946280069  938 IAIAEFDFNPSESNQLPLRKGcQVIVL---SKEGDYKGWWKGKVQD-RVGFFPKDYVR 991
Cdd:cd11864      1 VARAEYDFVAESEDELSFRAG-DKLRLapkELQPRVRGWLLATVDGqKIGLVPANYVK 57
MIA cd11890
Melanoma Inhibitory Activity protein; MIA is a single domain protein that adopts a Src ...
 938-993 4.57e-03

Melanoma Inhibitory Activity protein; MIA is a single domain protein that adopts a Src Homology 3 (SH3) domain-like fold; it contains an additional antiparallel beta sheet and two disulfide bonds compared to classical SH3 domains. MIA is secreted from malignant melanoma cells and it plays an important role in melanoma development and invasion. MIA is expressed by chondrocytes in normal tissues and may be important in the cartilage cell phenotype. Unlike classical SH3 domains, MIA does not bind proline-rich ligands. It binds peptide ligands with sequence similarity to type III human fibronectin repeats.


Pssm-ID: 212823  Cd Length: 98  Bit Score: 37.55  E-value: 4.57e-03
                           10        20        30        40        50        60
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 1946280069  938 IAIAEFDFNPSESNQLPLRKGCQVIVLSK-EGDYKGWWKGKVQD--------RVGFFPKDYVRET 993
Cdd:cd11890     15 IAVALQDYMAPDCRFIPIQRGQVVYVFSKlKGRGRLFWGGSVQGdyygeqaaRLGYFPSSIVQED 79
PH_puratrophin-1 cd13242
Puratrophin-1 pleckstrin homology (PH) domain; Puratrophin-1 (also called Purkinje cell ...
 564-685 4.79e-03

Puratrophin-1 pleckstrin homology (PH) domain; Puratrophin-1 (also called Purkinje cell atrophy-associated protein 1 or PLEKHG4/Pleckstrin homology domain-containing family G member 4) contains a spectrin repeat, a RhoGEF (DH) domain, and a PH domain. It is thought to function in intracellular signaling and cytoskeleton dynamics at the Golgi. Puratrophin-1 is expressed in kidney, Leydig cells in the testis, epithelial cells in the prostate gland and Langerhans islet in the pancreas. A single nucleotide substitution in the puratrophin-1 gene were once thought to result in autosomal dominant cerebellar ataxia (ADCA), but now it has been demonstrated that this ataxia is a result of defects in the BEAN gene. Puratrophin contains a domain architecture similar to that of Dbl family members Dbs and Trio. Dbs is a guanine nucleotide exchange factor (GEF), which contains spectrin repeats, a RhoGEF (DH) domain and a PH domain. The Dbs PH domain participates in binding to both the Cdc42 and RhoA GTPases. Trio plays an essential role in regulating the actin cytoskeleton during axonal guidance and branching. Trio is a multidomain signaling protein that contains two RhoGEF(DH)-PH domains in tandem. PH domains have diverse functions, but in general are involved in targeting proteins to the appropriate cellular location or in the interaction with a binding partner. They share little sequence conservation, but all have a common fold, which is electrostatically polarized. Less than 10% of PH domains bind phosphoinositide phosphates (PIPs) with high affinity and specificity. PH domains are distinguished from other PIP-binding domains by their specific high-affinity binding to PIPs with two vicinal phosphate groups: PtdIns(3,4)P2, PtdIns(4,5)P2 or PtdIns(3,4,5)P3 which results in targeting some PH domain proteins to the plasma membrane. A few display strong specificity in lipid binding. Any specificity is usually determined by loop regions or insertions in the N-terminus of the domain, which are not conserved across all PH domains. PH domains are found in cellular signaling proteins such as serine/threonine kinase, tyrosine kinases, regulators of G-proteins, endocytotic GTPases, adaptors, as well as cytoskeletal associated molecules and in lipid associated enzymes.


Pssm-ID: 270062  Cd Length: 136  Bit Score: 38.43  E-value: 4.79e-03
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1946280069  564 LRTDSISDLDMPenteLKDYGRLLKDGELKIKAHddQKIKTRYIFVFDQVIIMCKSLRGE----TYSYRESLRLQEYKI- 638
Cdd:cd13242     11 LAMDSIRGCDVN----LKEQGQLLRQDEFLVWQG--RKKCLRHVFLFEDLILFSKPKKTPggkdVYIYKHSIKTSDIGLt 84

                           90       100       110       120
                   ....*....|....*....|....*....|....*....|....*..
gi 1946280069  639 EDVhtrrtlrTDARWSYQFYLVRKSERTAYTLYARTEDNKRKWMKAI 685
Cdd:cd13242     85 ENV-------GDSGLKFEIWFRRRKARDTYILQATSPEIKQAWTSDI 124
C1_RASGRP2 cd20861
protein kinase C conserved region 1 (C1 domain) found in RAS guanyl-releasing protein 2 ...
 757-791 5.34e-03

protein kinase C conserved region 1 (C1 domain) found in RAS guanyl-releasing protein 2 (RASGRP2) and similar proteins; RASGRP2, also called calcium and DAG-regulated guanine nucleotide exchange factor I (CalDAG-GEFI), Cdc25-like protein (CDC25L), or F25B3.3 kinase-like protein, functions as a calcium- and DAG-regulated nucleotide exchange factor specifically activating Rap through the exchange of bound GDP for GTP. It may also activate other GTPases such as RRAS, RRAS2, NRAS, KRAS but not HRAS. RASGRP2 is also involved in aggregation of platelets and adhesion of T-lymphocytes and neutrophils probably through inside-out integrin activation, as well as in the muscarinic acetylcholine receptor M1/CHRM1 signaling pathway. The C1 domain is a cysteine-rich zinc binding domain that does not bind DNA nor possess structural similarity to conventional zinc finger domains; it contains two separate Zn(2+)-binding sites.


Pssm-ID: 410411  Cd Length: 56  Bit Score: 36.40  E-value: 5.34e-03
                           10        20        30
                   ....*....|....*....|....*....|....*
gi 1946280069  757 YLQATTCHHCSKFLKGIILQGYLCGECSIAVHKQC 791
Cdd:cd20861     11 FLRPVACRHCKNLILGIYKQGLKCRACGVNCHKQC 45
SH3_GRAP2_N cd11947
N-terminal Src homology 3 domain of GRB2-related adaptor protein 2; GRAP2 is also called GADS ...
 939-990 5.85e-03

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: 35.93  E-value: 5.85e-03
                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|..
gi 1946280069  939 AIAEFDFNPSESNQLPLRKGCQVIVLSKEGDykgWWKGKVQDRVGFFPKDYV 990
Cdd:cd11947      2 ARGKFDFTASGEDELSFKKGDVLKILSSDDI---WFKAELNGEEGYVPKNFV 50
PH1_FGD2 cd13386
FYVE, RhoGEF and PH domain containing/faciogenital dysplasia protein 2, N-terminal Pleckstrin ...
 586-693 6.27e-03

FYVE, RhoGEF and PH domain containing/faciogenital dysplasia protein 2, N-terminal Pleckstrin homology (PH) domain; In general, FGDs have a RhoGEF (DH) domain, followed by an N-terminal PH domain, a FYVE domain and a C-terminal PH domain. All FGDs are guanine nucleotide exchange factors that activates the Rho GTPase Cdc42, an important regulator of membrane trafficking. The RhoGEF domain is responsible for GEF catalytic activity, while the N-terminal PH domain is involved in intracellular targeting of the DH domain. Not much is known about FGD2. FGD1 is the best characterized member of the group with mutations here leading to the X-linked disorder known as faciogenital dysplasia (FGDY). PH domains have diverse functions, but in general are involved in targeting proteins to the appropriate cellular location or in the interaction with a binding partner. They share little sequence conservation, but all have a common fold, which is electrostatically polarized. Less than 10% of PH domains bind phosphoinositide phosphates (PIPs) with high affinity and specificity. PH domains are distinguished from other PIP-binding domains by their specific high-affinity binding to PIPs with two vicinal phosphate groups: PtdIns(3,4)P2, PtdIns(4,5)P2 or PtdIns(3,4,5)P3 which results in targeting some PH domain proteins to the plasma membrane. A few display strong specificity in lipid binding. Any specificity is usually determined by loop regions or insertions in the N-terminus of the domain, which are not conserved across all PH domains. PH domains are found in cellular signaling proteins such as serine/threonine kinase, tyrosine kinases, regulators of G-proteins, endocytotic GTPases, adaptors, as well as cytoskeletal associated molecules and in lipid associated enzymes.


Pssm-ID: 275421  Cd Length: 108  Bit Score: 37.59  E-value: 6.27e-03
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1946280069  586 LLKDGE-LKIKAHDDQKiKTRYIFVFDQVIIMCK---SLRGETYSYRESLRLQEYKIEDVHtrrtlrtDARWSYQFyLVR 661
Cdd:cd13386      1 LLKEGPvLKISFRNNNP-KERYLFLFNNMLLYCVpkvIQVGAKFQVHMRIDVDGMKVRELN-------DAEFPHSF-LVS 71

                           90       100       110
                   ....*....|....*....|....*....|..
gi 1946280069  662 KSERTaYTLYARTEDNKRKWMKAIHDAMDNLE 693
Cdd:cd13386     72 GKQRT-LELQARSQEEMEAWIQAFQEAIDQNE 102
SH2_DAPP1_BAM32_like cd10355
Src homology 2 domain found in dual adaptor for phosphotyrosine and 3-phosphoinositides ( ...
 831-885 6.49e-03

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


Pssm-ID: 198218  Cd Length: 92  Bit Score: 37.07  E-value: 6.49e-03
                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....*.
gi 1946280069  831 WFVGEMGRDRASA-LLERHMDGTYLLRvrpqgATHPNETIYALSLKTDDRVKHMKV 885
Cdd:cd10355      8 WYHGNLTRHAAEAlLLSNGVDGSYLLR-----NSNEGTGLFSLSVRAKDSVKHFHV 58
SH3_Eve1_3 cd11816
Third Src homology 3 domain of ADAM-binding protein Eve-1; Eve-1, also called SH3 ...
 939-990 6.93e-03

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


Pssm-ID: 212750 [Multi-domain]  Cd Length: 51  Bit Score: 35.85  E-value: 6.93e-03
                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|..
gi 1946280069  939 AIAEFDFNPSESNQLPLRKGCQVIVLSKEGDYkgWWKGKVQDRVGFFPKDYV 990
Cdd:cd11816      2 CVARFDFEGEQEDELSFSEGDVITLKEYVGEE--WAKGELNGKIGIFPLNFV 51
SH3_HS1 cd12073
Src homology 3 domain of Hematopoietic lineage cell-specific protein 1; HS1, also called HCLS1 ...
 937-991 7.07e-03

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


Pssm-ID: 213006 [Multi-domain]  Cd Length: 55  Bit Score: 35.96  E-value: 7.07e-03
                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....*
gi 1946280069  937 IIAIAEFDFNPSESNQLPLRKGcQVIVLSKEGDyKGWWKGKVQDRVGFFPKDYVR 991
Cdd:cd12073      1 ICAVALYDYQGEGDDEISFDPQ-ETITDIEMVD-EGWWKGTCHGHRGLFPANYVE 53
SH3_CD2AP_1 cd12053
First Src Homology 3 domain (SH3A) of CD2-associated protein; CD2AP, also called CMS (Cas ...
 940-992 7.64e-03

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


Pssm-ID: 212986  Cd Length: 56  Bit Score: 35.97  E-value: 7.64e-03
                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|...
gi 1946280069  940 IAEFDFNPSESNQLPLRKGcQVIVLSKEGDYKGWWKGKVQDRVGFFPKDYVRE 992
Cdd:cd12053      3 IVEYDYDAVHEDELTIRVG-EIIRNVKKLEEEGWLEGELNGRRGMFPDNFVKE 54
C1_PKD1_rpt2 cd20842
second protein kinase C conserved region 1 (C1 domain) found in protein kinase D (PKD) and ...
 702-733 7.76e-03

second protein kinase C conserved region 1 (C1 domain) found in protein kinase D (PKD) and similar proteins; PKD is also called PKD1, PRKD1, protein kinase C mu type (nPKC-mu), PRKCM, serine/threonine-protein kinase D1, or nPKC-D1. It is a serine/threonine-protein kinase that converts transient diacylglycerol (DAG) signals into prolonged physiological effects downstream of PKC, and is involved in the regulation of MAPK8/JNK1 and Ras signaling, Golgi membrane integrity and trafficking, cell survival through NF-kappa-B activation, cell migration, cell differentiation by mediating HDAC7 nuclear export, cell proliferation via MAPK1/3 (ERK1/2) signaling, and plays a role in cardiac hypertrophy, VEGFA-induced angiogenesis, genotoxic-induced apoptosis and flagellin-stimulated inflammatory response. PKD contains N-terminal tandem cysteine-rich zinc binding C1 (PKC conserved region 1), central PH (Pleckstrin Homology), and C-terminal catalytic kinase domains. This model corresponds to the second C1 domain. The C1 domain is a cysteine-rich zinc binding domain that does not bind DNA nor possess structural similarity to conventional zinc finger domains; it contains two separate Zn(2+)-binding sites.


Pssm-ID: 410392  Cd Length: 94  Bit Score: 36.92  E-value: 7.76e-03
                           10        20        30
                   ....*....|....*....|....*....|..
gi 1946280069  702 HTFKMNTFEQATTCHHCSKFLKGIILQVCTCR 733
Cdd:cd20842     35 HTFVIHSYTRPTVCQYCKKLLKGLFRQGLQCK 66
SH2_Src_Src42 cd10370
Src homology 2 (SH2) domain found in the Src oncogene at 42A (Src42); Src42 is a member of the ...
 831-933 8.22e-03

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


Pssm-ID: 198233  Cd Length: 96  Bit Score: 36.71  E-value: 8.22e-03
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1946280069  831 WFVGEMGRDRASA--LLERHMDGTYLLRvrpqgATHPNETIYALSLKTDDRVKHMKVYERTMEGvphYFLSESRFFRSIT 908
Cdd:cd10370      5 WYFGKIKRIEAEKklLLPENEHGAFLIR-----DSESRHNDYSLSVRDGDTVKHYRIRQLDEGG---FFIARRTTFRTLQ 76

                           90       100
                   ....*....|....*....|....*
gi 1946280069  909 DLIGCYEHSSlgenfVGLDVTLKWP 933
Cdd:cd10370     77 ELVEHYSKDS-----DGLCVNLRKP 96
SH3_Abi1 cd11971
Src homology 3 domain of Abl Interactor 1; Abi1, also called e3B1, is a central regulator of ...
 936-996 8.44e-03

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


Pssm-ID: 212904 [Multi-domain]  Cd Length: 59  Bit Score: 35.77  E-value: 8.44e-03
                           10        20        30        40        50        60
                   ....*....|....*....|....*....|....*....|....*....|....*....|.
gi 1946280069  936 RIIAIaeFDFNPSESNQLPLRKGCQVIVLSKEGDykGWWKGKVQDRVGFFPKDYVRETLGY 996
Cdd:cd11971      1 KVVAI--YDYSKDKDDELSFMEGAIIYVIKKNDD--GWYEGVCNGVTGLFPGNYVESIMHY 57
 
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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