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Conserved domains on  [gi|568918593|ref|XP_006500332|]
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ras and Rab interactor 2 isoform X1 [Mus musculus]

Protein Classification

SH2_RIN2 and RA_Rin2 domain-containing protein( domain architecture ID 12970115)

protein containing domains SH2_RIN2, VPS9, and RA_Rin2

Graphical summary

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List of domain hits

 Name Accession Description Interval E-value
SH2_RIN2 cd10394
Src homology 2 (SH2) domain found in Ras and Rab interactor 2 (RIN2)-like proteins; RIN2, a ...
 86-185 1.13e-62

Src homology 2 (SH2) domain found in Ras and Rab interactor 2 (RIN2)-like proteins; RIN2, a member of the RIN (AKA Ras interaction/interference) family, have multifunctional domains including SH2 and proline-rich (PR) domains in the N-terminal region, and RIN-family homology (RH), VPS9 and Ras-association (RA) domains in the C-terminal region. RIN proteins function as Rab5-GEFs. Ras induces activation of Rab5 through RIN2, which is a direct downstream target of Ras and a direct upstream regulator of Rab5. In other words it is the binding of the GTP-bound form of Ras to the RA domain of RIN2 that enhances the GEF activity toward Rab5. It is thought that the RA domain negatively regulates the Rab5 GEF activity. In steady state, RIN2 is likely to form a closed conformation by an intramolecular interaction between the RA domain and the Vps9p-like (Rab5 GEF) domain, negatively regulating the Rab5 GEF activity. In the active state, the binding of Ras to the RA domain may reduce the intramolecular interaction and stabilize an open conformation of RIN2. 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: 198257  Cd Length: 100  Bit Score: 206.20  E-value: 1.13e-62
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568918593  86 ILDRLLHTHPIWLQLSLSEEEAAEVLQAQPPGIFLVRKSSKMQKKVLSLRLPCEFGAPLKEFTIKESTYTFSLEGSGISF 165
Cdd:cd10394    1 ILDRLLHTHPIWLQLSLSEEEAAEVLQAQPPGIFLVRKSSKMQKKVLSLRLPCEFGAPLKEFAIKESTYTFSLEGSGISF 80

                         90       100
                 ....*....|....*....|
gi 568918593 166 ADLFRLIAFYCISRDVLPFT 185
Cdd:cd10394   81 ADLFRLIAFYCISRDVLPFT 100
RA_Rin2 cd16131
Ras-associating (RA) domain found in Ras and Rab interactor 2 (Rin2); Rin2, also termed Ras ...
 796-886 2.52e-62

Ras-associating (RA) domain found in Ras and Rab interactor 2 (Rin2); Rin2, also termed Ras association domain family 4, or Ras inhibitor JC265, or Ras interaction/interference protein 2, is a Rab5 GDP/GTP exchange factor with the Vps9p-like guanine nucleotide exchange factor and Ras-association (RA) domains. Rin2 connects three GTPases, R-Ras, Rab5 and Rac1, to promote endothelial cell adhesion through the regulation of integrin internalization and Rac1 activation. Rin2 is involved in the regulation of Rab5-mediated early endocytosis. The deficiency of Rin2 can cause the RIN2 syndrome, an autosomal recessive connective tissue disorder.


:

Pssm-ID: 340548  Cd Length: 91  Bit Score: 205.09  E-value: 2.52e-62
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568918593 796 FQNYLRVAFQEVNSGCTGKTLLVRPYITTEDVCQLCAEKFKVEDPEEYSLFLFVDETWQQLAEDTYPQKIKAELHSRPQP 875
Cdd:cd16131    1 FQNYLRVAFQEVNSGCTAKTLLVRPYTTTEEVCQLCAQKFKVQDPENYSLFLLIDDTWQQLAEDTYPQKIKAELHSRPQP 80

                         90
                 ....*....|.
gi 568918593 876 HIFHFVYKRIK 886
Cdd:cd16131   81 QIFHFVYKRIP 91
VPS9 smart00167
Domain present in VPS9; Domain present in yeast vacuolar sorting protein 9 and other proteins.
 659-775 7.58e-50

Domain present in VPS9; Domain present in yeast vacuolar sorting protein 9 and other proteins.


:

Pssm-ID: 128469  Cd Length: 117  Bit Score: 171.48  E-value: 7.58e-50
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568918593   659 ELEKIKLKFMTMQKmySPEKKVMLLLRVCKLIYTVMENNSGRMYGADDFLPVLTYVIAQCDMLELDTEIEYMMELLDPSL 738
Cdd:smart00167   3 EIEQIELKFLQLYK--SPSDKIKCLLRACKLIYTLLETQSGEVAGADDFLPVLIYVIIKCDPRDLLLNAEYMEEFLEPSL 80

                           90       100       110
                   ....*....|....*....|....*....|....*..
gi 568918593   739 LHGEGGYYLTSAYGALSLIKNFQEEQAARLLSSEARD 775
Cdd:smart00167  81 LTGEGGYYLTSLSAALALIKGLTEAHALPLSPEQELE 117
 
Name Accession Description Interval E-value
SH2_RIN2 cd10394
Src homology 2 (SH2) domain found in Ras and Rab interactor 2 (RIN2)-like proteins; RIN2, a ...
 86-185 1.13e-62

Src homology 2 (SH2) domain found in Ras and Rab interactor 2 (RIN2)-like proteins; RIN2, a member of the RIN (AKA Ras interaction/interference) family, have multifunctional domains including SH2 and proline-rich (PR) domains in the N-terminal region, and RIN-family homology (RH), VPS9 and Ras-association (RA) domains in the C-terminal region. RIN proteins function as Rab5-GEFs. Ras induces activation of Rab5 through RIN2, which is a direct downstream target of Ras and a direct upstream regulator of Rab5. In other words it is the binding of the GTP-bound form of Ras to the RA domain of RIN2 that enhances the GEF activity toward Rab5. It is thought that the RA domain negatively regulates the Rab5 GEF activity. In steady state, RIN2 is likely to form a closed conformation by an intramolecular interaction between the RA domain and the Vps9p-like (Rab5 GEF) domain, negatively regulating the Rab5 GEF activity. In the active state, the binding of Ras to the RA domain may reduce the intramolecular interaction and stabilize an open conformation of RIN2. 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: 198257  Cd Length: 100  Bit Score: 206.20  E-value: 1.13e-62
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568918593  86 ILDRLLHTHPIWLQLSLSEEEAAEVLQAQPPGIFLVRKSSKMQKKVLSLRLPCEFGAPLKEFTIKESTYTFSLEGSGISF 165
Cdd:cd10394    1 ILDRLLHTHPIWLQLSLSEEEAAEVLQAQPPGIFLVRKSSKMQKKVLSLRLPCEFGAPLKEFAIKESTYTFSLEGSGISF 80

                         90       100
                 ....*....|....*....|
gi 568918593 166 ADLFRLIAFYCISRDVLPFT 185
Cdd:cd10394   81 ADLFRLIAFYCISRDVLPFT 100
RA_Rin2 cd16131
Ras-associating (RA) domain found in Ras and Rab interactor 2 (Rin2); Rin2, also termed Ras ...
 796-886 2.52e-62

Ras-associating (RA) domain found in Ras and Rab interactor 2 (Rin2); Rin2, also termed Ras association domain family 4, or Ras inhibitor JC265, or Ras interaction/interference protein 2, is a Rab5 GDP/GTP exchange factor with the Vps9p-like guanine nucleotide exchange factor and Ras-association (RA) domains. Rin2 connects three GTPases, R-Ras, Rab5 and Rac1, to promote endothelial cell adhesion through the regulation of integrin internalization and Rac1 activation. Rin2 is involved in the regulation of Rab5-mediated early endocytosis. The deficiency of Rin2 can cause the RIN2 syndrome, an autosomal recessive connective tissue disorder.


Pssm-ID: 340548  Cd Length: 91  Bit Score: 205.09  E-value: 2.52e-62
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568918593 796 FQNYLRVAFQEVNSGCTGKTLLVRPYITTEDVCQLCAEKFKVEDPEEYSLFLFVDETWQQLAEDTYPQKIKAELHSRPQP 875
Cdd:cd16131    1 FQNYLRVAFQEVNSGCTAKTLLVRPYTTTEEVCQLCAQKFKVQDPENYSLFLLIDDTWQQLAEDTYPQKIKAELHSRPQP 80

                         90
                 ....*....|.
gi 568918593 876 HIFHFVYKRIK 886
Cdd:cd16131   81 QIFHFVYKRIP 91
VPS9 smart00167
Domain present in VPS9; Domain present in yeast vacuolar sorting protein 9 and other proteins.
 659-775 7.58e-50

Domain present in VPS9; Domain present in yeast vacuolar sorting protein 9 and other proteins.


Pssm-ID: 128469  Cd Length: 117  Bit Score: 171.48  E-value: 7.58e-50
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568918593   659 ELEKIKLKFMTMQKmySPEKKVMLLLRVCKLIYTVMENNSGRMYGADDFLPVLTYVIAQCDMLELDTEIEYMMELLDPSL 738
Cdd:smart00167   3 EIEQIELKFLQLYK--SPSDKIKCLLRACKLIYTLLETQSGEVAGADDFLPVLIYVIIKCDPRDLLLNAEYMEEFLEPSL 80

                           90       100       110
                   ....*....|....*....|....*....|....*..
gi 568918593   739 LHGEGGYYLTSAYGALSLIKNFQEEQAARLLSSEARD 775
Cdd:smart00167  81 LTGEGGYYLTSLSAALALIKGLTEAHALPLSPEQELE 117
VPS9 pfam02204
Vacuolar sorting protein 9 (VPS9) domain; This domain acts as a GDP-GTP exchange factor (GEF). ...
 660-761 1.30e-25

Vacuolar sorting protein 9 (VPS9) domain; This domain acts as a GDP-GTP exchange factor (GEF). It activates Rab GTPases by stimulating the release of GDP and allowing GTP to bind.


Pssm-ID: 460489  Cd Length: 104  Bit Score: 101.90  E-value: 1.30e-25
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568918593  660 LEKIKLKFMTMQKMYSPEKKVMLLLRVCKLIYTVMEN-NSGRMYGADDFLPVLTYVIAQCDMLELDTEIEYMMELLDPSL 738
Cdd:pfam02204   1 WEQAQQELKKLNEAKSPREKLKCLLRTCKLITEALSKsNRDESLGADDLLPILIYVLIRANPPNLYSNLQFISEFRDPDL 80

                          90       100
                  ....*....|....*....|...
gi 568918593  739 LHGEGGYYLTSAYGALSLIKNFQ 761
Cdd:pfam02204  81 LSGEEGYYLTTLEAALEFIESLD 103
RA pfam00788
Ras association (RalGDS/AF-6) domain; RasGTP effectors (in cases of AF6, canoe and RalGDS); ...
 796-884 7.36e-16

Ras association (RalGDS/AF-6) domain; RasGTP effectors (in cases of AF6, canoe and RalGDS); putative RasGTP effectors in other cases. Recent evidence (not yet in MEDLINE) shows that some RA domains do NOT bind RasGTP. Predicted structure similar to that determined, and that of the RasGTP-binding domain of Raf kinase.


Pssm-ID: 425871  Cd Length: 93  Bit Score: 73.52  E-value: 7.36e-16
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568918593  796 FQNYLRVAFQEVNSGCTGKTLLVRPYITTEDVCQLCAEKFKVE-DPEEYSLFLFV--DETWQQLAEDTYPQKIKAELHSR 872
Cdd:pfam00788   1 DDGVLKVYTEDGKPGTTYKTILVSSSTTAEEVIEALLEKFGLEdDPRDYVLVEVLerGGGERRLPDDECPLQIQLQWPRD 80

                          90
                  ....*....|..
gi 568918593  873 pqPHIFHFVYKR 884
Cdd:pfam00788  81 --ASDSRFLLRK 90
RA smart00314
Ras association (RalGDS/AF-6) domain; RasGTP effectors (in cases of AF6, canoe and RalGDS); ...
 796-884 3.76e-14

Ras association (RalGDS/AF-6) domain; RasGTP effectors (in cases of AF6, canoe and RalGDS); putative RasGTP effectors in other cases. Kalhammer et al. have shown that not all RA domains bind RasGTP. Predicted structure similar to that determined, and that of the RasGTP-binding domain of Raf kinase. Predicted RA domains in PLC210 and nore1 found to bind RasGTP. Included outliers (Grb7, Grb14, adenylyl cyclases etc.)


Pssm-ID: 214612  Cd Length: 90  Bit Score: 68.48  E-value: 3.76e-14
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568918593   796 FQNYLRVAFQeVNSGCTGKTLLVRPYITTEDVCQLCAEKFKVED-PEEYSLFLFV-DETWQQLAEDTYPQKIKAELHsrP 873
Cdd:smart00314   1 DTFVLRVYVD-DLPGGTYKTLRVSSRTTARDVIQQLLEKFHLTDdPEEYVLVEVLpDGKERVLPDDENPLQLQKLWP--R 77

                           90
                   ....*....|.
gi 568918593   874 QPHIFHFVYKR 884
Cdd:smart00314  78 RGPNLRFVLRK 88
SH2 smart00252
Src homology 2 domains; Src homology 2 domains bind phosphotyrosine-containing polypeptides ...
 102-175 5.64e-05

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: 42.22  E-value: 5.64e-05
                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 568918593   102 LSEEEAAEVLQAQPPGIFLVRKSSKMQKK-VLSLRlpceFGAPLKEFTIKESTY-TFSLEGsGISFADLFRLIAFY 175
Cdd:smart00252   8 ISREEAEKLLKNEGDGDFLVRDSESSPGDyVLSVR----VKGKVKHYRIRRNEDgKFYLEG-GRKFPSLVELVEHY 78
 
Name Accession Description Interval E-value
SH2_RIN2 cd10394
Src homology 2 (SH2) domain found in Ras and Rab interactor 2 (RIN2)-like proteins; RIN2, a ...
 86-185 1.13e-62

Src homology 2 (SH2) domain found in Ras and Rab interactor 2 (RIN2)-like proteins; RIN2, a member of the RIN (AKA Ras interaction/interference) family, have multifunctional domains including SH2 and proline-rich (PR) domains in the N-terminal region, and RIN-family homology (RH), VPS9 and Ras-association (RA) domains in the C-terminal region. RIN proteins function as Rab5-GEFs. Ras induces activation of Rab5 through RIN2, which is a direct downstream target of Ras and a direct upstream regulator of Rab5. In other words it is the binding of the GTP-bound form of Ras to the RA domain of RIN2 that enhances the GEF activity toward Rab5. It is thought that the RA domain negatively regulates the Rab5 GEF activity. In steady state, RIN2 is likely to form a closed conformation by an intramolecular interaction between the RA domain and the Vps9p-like (Rab5 GEF) domain, negatively regulating the Rab5 GEF activity. In the active state, the binding of Ras to the RA domain may reduce the intramolecular interaction and stabilize an open conformation of RIN2. 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: 198257  Cd Length: 100  Bit Score: 206.20  E-value: 1.13e-62
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568918593  86 ILDRLLHTHPIWLQLSLSEEEAAEVLQAQPPGIFLVRKSSKMQKKVLSLRLPCEFGAPLKEFTIKESTYTFSLEGSGISF 165
Cdd:cd10394    1 ILDRLLHTHPIWLQLSLSEEEAAEVLQAQPPGIFLVRKSSKMQKKVLSLRLPCEFGAPLKEFAIKESTYTFSLEGSGISF 80

                         90       100
                 ....*....|....*....|
gi 568918593 166 ADLFRLIAFYCISRDVLPFT 185
Cdd:cd10394   81 ADLFRLIAFYCISRDVLPFT 100
RA_Rin2 cd16131
Ras-associating (RA) domain found in Ras and Rab interactor 2 (Rin2); Rin2, also termed Ras ...
 796-886 2.52e-62

Ras-associating (RA) domain found in Ras and Rab interactor 2 (Rin2); Rin2, also termed Ras association domain family 4, or Ras inhibitor JC265, or Ras interaction/interference protein 2, is a Rab5 GDP/GTP exchange factor with the Vps9p-like guanine nucleotide exchange factor and Ras-association (RA) domains. Rin2 connects three GTPases, R-Ras, Rab5 and Rac1, to promote endothelial cell adhesion through the regulation of integrin internalization and Rac1 activation. Rin2 is involved in the regulation of Rab5-mediated early endocytosis. The deficiency of Rin2 can cause the RIN2 syndrome, an autosomal recessive connective tissue disorder.


Pssm-ID: 340548  Cd Length: 91  Bit Score: 205.09  E-value: 2.52e-62
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568918593 796 FQNYLRVAFQEVNSGCTGKTLLVRPYITTEDVCQLCAEKFKVEDPEEYSLFLFVDETWQQLAEDTYPQKIKAELHSRPQP 875
Cdd:cd16131    1 FQNYLRVAFQEVNSGCTAKTLLVRPYTTTEEVCQLCAQKFKVQDPENYSLFLLIDDTWQQLAEDTYPQKIKAELHSRPQP 80

                         90
                 ....*....|.
gi 568918593 876 HIFHFVYKRIK 886
Cdd:cd16131   81 QIFHFVYKRIP 91
SH2_RIN_family cd10339
Src homology 2 (SH2) domain found in Ras and Rab interactor (RIN)-family; The RIN (AKA Ras ...
 86-185 5.87e-52

Src homology 2 (SH2) domain found in Ras and Rab interactor (RIN)-family; The RIN (AKA Ras interaction/interference) family is composed of RIN1, RIN2 and RIN3. These proteins have multifunctional domains including SH2 and proline-rich (PR) domains in the N-terminal region, and RIN-family homology (RH), VPS9 and Ras-association (RA) domains in the C-terminal region. RIN proteins function as Rab5-GEFs, and RIN3 specifically functions as a Rab31-GEF. 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: 198202  Cd Length: 101  Bit Score: 176.57  E-value: 5.87e-52
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568918593  86 ILDRLLHTHPIWLQLSLSEEEAAEVLQAQPPGIFLVRKSSKMQKKVLSLRLPC-EFGAPLKEFTIKESTYTFSLEGSGIS 164
Cdd:cd10339    1 LLERLLLTRPVWLQLQLNAAEAAHMLQTEPPGTFLVRKSNTRQCQVLCMRLPEaSGPAFVSEHYIKESPGGVSLEGSELM 80

                         90       100
                 ....*....|....*....|.
gi 568918593 165 FADLFRLIAFYCISRDVLPFT 185
Cdd:cd10339   81 FPDLFRLIAFYCHSRDILPFT 101
VPS9 smart00167
Domain present in VPS9; Domain present in yeast vacuolar sorting protein 9 and other proteins.
 659-775 7.58e-50

Domain present in VPS9; Domain present in yeast vacuolar sorting protein 9 and other proteins.


Pssm-ID: 128469  Cd Length: 117  Bit Score: 171.48  E-value: 7.58e-50
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568918593   659 ELEKIKLKFMTMQKmySPEKKVMLLLRVCKLIYTVMENNSGRMYGADDFLPVLTYVIAQCDMLELDTEIEYMMELLDPSL 738
Cdd:smart00167   3 EIEQIELKFLQLYK--SPSDKIKCLLRACKLIYTLLETQSGEVAGADDFLPVLIYVIIKCDPRDLLLNAEYMEEFLEPSL 80

                           90       100       110
                   ....*....|....*....|....*....|....*..
gi 568918593   739 LHGEGGYYLTSAYGALSLIKNFQEEQAARLLSSEARD 775
Cdd:smart00167  81 LTGEGGYYLTSLSAALALIKGLTEAHALPLSPEQELE 117
RA_Rin cd01776
Ras-associating (RA) domain of Ras and Rab interactor (Rin) protein family; Family of ...
 797-886 1.14e-34

Ras-associating (RA) domain of Ras and Rab interactor (Rin) protein family; Family of Ras-interaction/interference (Rin) proteins, also known as Ras and Rab interactors, is composed of Rin1, Rin2, and Rin3, which have multifunctional domains, including SH2 and proline-rich domains in the N-terminal region, and RH, VPS9, and RA domains in the C-terminal region. RA domain-containing proteins function by interacting with Ras proteins directly or indirectly and are involved in several different functions ranging from tumor suppression to being oncoproteins. Ras proteins are small GTPases that are involved in cellular signal transduction. The RA domain has the beta-grasp ubiquitin-like (Ubl) fold with low sequence similarity to ubiquitin; ubiquitin is a protein modifier in eukaryotes that is involved in various cellular processes including transcriptional regulation, cell cycle control, and DNA repair. The RA domains of Rin1, Rin2, and Rin3 are well conserved and they all have Ras binding characteristics.


Pssm-ID: 340474  Cd Length: 90  Bit Score: 127.03  E-value: 1.14e-34
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568918593 797 QNYLRVAFQEV-NSGCTGKTLLVRPYITTEDVCQLCAEKFKVEDPEEYSLFLFVDETWQQLAEDTYPQKIKAELHSRPQP 875
Cdd:cd01776    1 QGFLRVAVPDEnNGSIVSKTLPVRPSMTAREVCKMIAHKFRVTNPQDYGLFLLVDGEEIQLEDNECPQLIKGELLATSKK 80

                         90
                 ....*....|.
gi 568918593 876 HiFHFVYKRIK 886
Cdd:cd01776   81 P-CYFAYKRID 90
SH2_RIN3 cd10395
Src homology 2 (SH2) domain found in Ras and Rab interactor 3 (RIN3)-like proteins; RIN3, a ...
 86-185 1.56e-32

Src homology 2 (SH2) domain found in Ras and Rab interactor 3 (RIN3)-like proteins; RIN3, a member of the RIN (AKA Ras interaction/interference) family, have multifunctional domains including SH2 and proline-rich (PR) domains in the N-terminal region, and RIN-family homology (RH), VPS9 and Ras-association (RA) domains in the C-terminal region. RIN proteins function as Rab5-GEFs. RIN3 stimulated the formation of GTP-bound Rab31, a Rab5-subfamily GTPase, and formed enlarged vesicles and tubular structures, where it colocalized with Rab31. Transferrin appeared to be transported partly through the RIN3-positive vesicles to early endosomes. RIN3 interacts via its Pro-rich domain with amphiphysin II, which contains SH3 domain and participates in receptor-mediated endocytosis. RIN3, a Rab5 and Rab31 GEF, plays an important role in the transport pathway from plasma membrane to early endosomes. Mutations in the region between the SH2 and RH domain of RIN3 specifically abolished its GEF action on Rab31, but not Rab5. RIN3 was also found to partially translocate the cation-dependent mannose 6-phosphate receptor from the trans-Golgi network to peripheral vesicles and that this is dependent on its Rab31-GEF activity. These data indicate that RIN3 specifically acts as a GEF for Rab31. 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: 198258  Cd Length: 101  Bit Score: 121.42  E-value: 1.56e-32
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568918593  86 ILDRLLHTHPIWLQLSLSEEEAAEVLQAQPPGIFLVRKSSKMQKKVLSLRLPCEFGAP-LKEFTIKESTYTFSLEGSGIS 164
Cdd:cd10395    1 ILEKLIKTCPVWLQLGMNQAEAARILHKEVAGMFLVRRDSNSKQMVLCVHFPSNESSAeVLEYPIKEEKSILYLEGSVLV 80

                         90       100
                 ....*....|....*....|.
gi 568918593 165 FADLFRLIAFYCISRDVLPFT 185
Cdd:cd10395   81 FEDIFKLIAFYCVSRDLLPFT 101
SH2_RIN1 cd10393
Src homology 2 (SH2) domain found in Ras and Rab interactor 1 (RIN1)-like proteins; RIN1, a ...
 86-185 2.35e-30

Src homology 2 (SH2) domain found in Ras and Rab interactor 1 (RIN1)-like proteins; RIN1, a member of the RIN (AKA Ras interaction/interference) family, have multifunctional domains including SH2 and proline-rich (PR) domains in the N-terminal region, and RIN-family homology (RH), VPS9 and Ras-association (RA) domains in the C-terminal region. RIN proteins function as Rab5-GEFs. Previous studies showed that RIN1 interacts with EGF receptors via its SH2 domain and regulates trafficking and degradation of EGF receptors via its interaction with STAM, indicating a vital role for RIN1 in regulating endosomal trafficking of receptor tyrosine kinases (RTKs). RIN1 was first identified as a Ras-binding protein that suppresses the activated RAS2 allele in S. cerevisiae. RIN1 binds to the activated Ras through its carboxyl-terminal domain and this Ras-binding domain also binds to 14-3-3 proteins as Raf-1 does. The SH2 domain of RIN1 are thought to interact with the phosphotyrosine-containing proteins, but the physiological partners for this domain are unknown. The proline-rich domain in RIN1 is similar to the consensus SH3 binding regions. In general SH2 domains are involved in signal transduction. They typically bind pTyr-containing ligands via two surface pockets, a pTyr and hydrophobic binding pocket, allowing proteins with SH2 domains to localize to tyrosine phosphorylated sites.


Pssm-ID: 198256  Cd Length: 101  Bit Score: 115.34  E-value: 2.35e-30
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568918593  86 ILDRLLHTHPIWLQLSLSEEEAAEVLQAQPPGIFLVRKSSKMQKKVLSLRLPCEFGAP-LKEFTIKESTYTFSLEGSGIS 164
Cdd:cd10393    1 LRERLLLTRPVWLQLRANAAAALHVLRTEPPGTFLVRKSNTRQCQALCVRLPEASGPSfVSSHYIQESPGGVSLEGSELT 80

                         90       100
                 ....*....|....*....|.
gi 568918593 165 FADLFRLIAFYCISRDVLPFT 185
Cdd:cd10393   81 FPDLVQLICAYCHTRDILLLP 101
RA_Rin3 cd16130
Ras-associating (RA) domain found in Ras and Rab interactor 3 (Rin3); Rin3, also termed Ras ...
 797-885 9.82e-27

Ras-associating (RA) domain found in Ras and Rab interactor 3 (Rin3); Rin3, also termed Ras interaction/interference protein 3, is a RAS effector and a RAB5-activating guanine nucleotide exchange factor (GEF) specifically for GTPase Rab31. It functions as a negative regulator of mast cell responses to Stem Cell Factor (SCF). Rin3 contains the Vps9p-like guanine nucleotide exchange factor and Ras-association (RA) domains.


Pssm-ID: 340547  Cd Length: 88  Bit Score: 104.42  E-value: 9.82e-27
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568918593 797 QNYLRVAFQEVnsGCTGKTLLVRPYITTEDVCQLCAEKFKVEDPEEYSLFLFVDETWQQLAEDTYPQKIKAELHSRPQPH 876
Cdd:cd16130    1 QDFISVSFLEP--GSNTRTLAIRPDTTAEDLCKQCAEKFEVLDPENYGLFVLVDGRCLQLADDALPHHIKSDLLKSEPRK 78


                 ....*....
gi 568918593 877 IFHFVYKRI 885
Cdd:cd16130   79 DFHFLYKQL 87
VPS9 pfam02204
Vacuolar sorting protein 9 (VPS9) domain; This domain acts as a GDP-GTP exchange factor (GEF). ...
 660-761 1.30e-25

Vacuolar sorting protein 9 (VPS9) domain; This domain acts as a GDP-GTP exchange factor (GEF). It activates Rab GTPases by stimulating the release of GDP and allowing GTP to bind.


Pssm-ID: 460489  Cd Length: 104  Bit Score: 101.90  E-value: 1.30e-25
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568918593  660 LEKIKLKFMTMQKMYSPEKKVMLLLRVCKLIYTVMEN-NSGRMYGADDFLPVLTYVIAQCDMLELDTEIEYMMELLDPSL 738
Cdd:pfam02204   1 WEQAQQELKKLNEAKSPREKLKCLLRTCKLITEALSKsNRDESLGADDLLPILIYVLIRANPPNLYSNLQFISEFRDPDL 80

                          90       100
                  ....*....|....*....|...
gi 568918593  739 LHGEGGYYLTSAYGALSLIKNFQ 761
Cdd:pfam02204  81 LSGEEGYYLTTLEAALEFIESLD 103
RA_Rin1 cd17215
Ras-associating (RA) domain found in Ras and Rab interactor 1 (Rin1); Rin1, also termed Ras ...
 797-884 3.81e-24

Ras-associating (RA) domain found in Ras and Rab interactor 1 (Rin1); Rin1, also termed Ras inhibitor JC99, or Ras interaction/interference protein 1, is a downstream Ras effector that represents a unique class of Ras effector connected to two independent signaling pathways. The first effector pathway is the direct activation of RAB5-mediated endocytosis and the second pathway involves direct activation of ABL tyrosine kinase activity. Rin1 functions as a guanine nucleotide exchange factor (GEF) for RAB5 GTPases. The RAB5 GEF activity of Rin1 promotes early endosome fusion, an early event in transit to the lysosome. Rin1 binds the SH3 and SH2 domains of ABL proteins, ABL1 and ABL2, and activates their tyrosine kinase activity. Rin1 contains SH2 and proline-rich domains in the N-terminal region, and RH, VPS9, and RA domains in the C-terminal region. The RA domain has the beta-grasp ubiquitin-like (Ubl) fold with low sequence similarity to ubiquitin; ubiquitin is a protein modifier in eukaryotes that is involved in various cellular processes including transcriptional regulation, cell cycle control, and DNA repair.


Pssm-ID: 340735  Cd Length: 88  Bit Score: 96.97  E-value: 3.81e-24
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568918593 797 QNYLRVAFQEVNSGCTGKTLLVRPYITTEDVCQLCAEKFKVEDPEEYSLFLFVDETWQQLAEDTYPQKIKAELhsRPQPH 876
Cdd:cd17215    1 QNFLRVAYQDPSSGCTSKTLAVPPSATVADLNQLCATKFKVTQPETYGIFLYKEQGYQRLPPDALPQRIKAQL--KEKGS 78


                 ....*...
gi 568918593 877 IFHFVYKR 884
Cdd:cd17215   79 TFYFVYQR 86
RA cd17043
Ras-associating (RA) domain, structurally similar to a beta-grasp ubiquitin-like fold; RA ...
 799-884 3.04e-17

Ras-associating (RA) domain, structurally similar to a beta-grasp ubiquitin-like fold; RA domain-containing proteins function by interacting with Ras proteins directly or indirectly and are involved in various functions ranging from tumor suppression to being oncoproteins. Ras proteins are small GTPases that are involved in cellular signal transduction. The RA domain has the beta-grasp ubiquitin-like (Ubl) fold with low sequence similarity to ubiquitin (Ub); Ub is a protein modifier in eukaryotes that is involved in various cellular processes, including transcriptional regulation, cell cycle control, and DNA repair. RA-containing proteins include RalGDS, AF6, RIN, RASSF1, SNX27, CYR1, STE50, and phospholipase C epsilon.


Pssm-ID: 340563  Cd Length: 87  Bit Score: 77.36  E-value: 3.04e-17
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568918593 799 YLRVAFQEVNSGCTGKTLLVRPYITTEDVCQLCAEKFKV-EDPEEYSLFLFVD--ETWQQLAEDTYPQKIKAElhSRPQP 875
Cdd:cd17043    1 VLKVYDDDLAPGSAYKSILVSSTTTAREVVQLLLEKYGLeEDPEDYSLYEVSEkqETERVLHDDECPLLIQLE--WGPQG 78


                 ....*....
gi 568918593 876 HIFHFVYKR 884
Cdd:cd17043   79 TEFRFVLKR 87
RA pfam00788
Ras association (RalGDS/AF-6) domain; RasGTP effectors (in cases of AF6, canoe and RalGDS); ...
 796-884 7.36e-16

Ras association (RalGDS/AF-6) domain; RasGTP effectors (in cases of AF6, canoe and RalGDS); putative RasGTP effectors in other cases. Recent evidence (not yet in MEDLINE) shows that some RA domains do NOT bind RasGTP. Predicted structure similar to that determined, and that of the RasGTP-binding domain of Raf kinase.


Pssm-ID: 425871  Cd Length: 93  Bit Score: 73.52  E-value: 7.36e-16
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568918593  796 FQNYLRVAFQEVNSGCTGKTLLVRPYITTEDVCQLCAEKFKVE-DPEEYSLFLFV--DETWQQLAEDTYPQKIKAELHSR 872
Cdd:pfam00788   1 DDGVLKVYTEDGKPGTTYKTILVSSSTTAEEVIEALLEKFGLEdDPRDYVLVEVLerGGGERRLPDDECPLQIQLQWPRD 80

                          90
                  ....*....|..
gi 568918593  873 pqPHIFHFVYKR 884
Cdd:pfam00788  81 --ASDSRFLLRK 90
RA smart00314
Ras association (RalGDS/AF-6) domain; RasGTP effectors (in cases of AF6, canoe and RalGDS); ...
 796-884 3.76e-14

Ras association (RalGDS/AF-6) domain; RasGTP effectors (in cases of AF6, canoe and RalGDS); putative RasGTP effectors in other cases. Kalhammer et al. have shown that not all RA domains bind RasGTP. Predicted structure similar to that determined, and that of the RasGTP-binding domain of Raf kinase. Predicted RA domains in PLC210 and nore1 found to bind RasGTP. Included outliers (Grb7, Grb14, adenylyl cyclases etc.)


Pssm-ID: 214612  Cd Length: 90  Bit Score: 68.48  E-value: 3.76e-14
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568918593   796 FQNYLRVAFQeVNSGCTGKTLLVRPYITTEDVCQLCAEKFKVED-PEEYSLFLFV-DETWQQLAEDTYPQKIKAELHsrP 873
Cdd:smart00314   1 DTFVLRVYVD-DLPGGTYKTLRVSSRTTARDVIQQLLEKFHLTDdPEEYVLVEVLpDGKERVLPDDENPLQLQKLWP--R 77

                           90
                   ....*....|.
gi 568918593   874 QPHIFHFVYKR 884
Cdd:smart00314  78 RGPNLRFVLRK 88
SH2 cd00173
Src homology 2 (SH2) domain; In general, SH2 domains are involved in signal transduction; they ...
 97-175 1.21e-07

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: 49.76  E-value: 1.21e-07
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568918593  97 WLQLSLSEEEAAEVLQAQPPGIFLVRKSSKMQKK-VLSLRlpCEFGAPlKEFTIKESTYTFSLEG-SGISFADLFRLIAF 174
Cdd:cd00173    2 WFHGSISREEAERLLRGKPDGTFLVRESSSEPGDyVLSVR--SGDGKV-KHYLIERNEGGYYLLGgSGRTFPSLPELVEH 78


                 .
gi 568918593 175 Y 175
Cdd:cd00173   79 Y 79
SH2_Grb7_family cd09944
Src homology 2 (SH2) domain found in the growth factor receptor bound, subclass 7 (Grb7) ...
 91-187 1.25e-07

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


Pssm-ID: 198197 [Multi-domain]  Cd Length: 108  Bit Score: 50.88  E-value: 1.25e-07
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568918593  91 LHTHPIWLQLSLSEEEAAEVLQAQ--PPGIFLVRKS-SKMQKKVLSLRlpceFGAPLKEFTI----KESTYTFSLEGSGI 163
Cdd:cd09944    1 IHRSQPWFHGGISRDEAARLIRQQglVDGVFLVRESqSNPGAFVLSLK----HGQKIKHYQIipieDEGQWYFTLDDGVT 76

                         90       100
                 ....*....|....*....|....
gi 568918593 164 SFADLFRLIAFYCISRDVLPFTLK 187
Cdd:cd09944   77 KFYDLLQLVEFYQLNAGSLPTRLK 100
SH2_Grb14 cd10414
Src homology 2 (SH2) domain found in the growth factor receptor bound, subclass 14 (Grb14) ...
 91-187 6.94e-07

Src homology 2 (SH2) domain found in the growth factor receptor bound, subclass 14 (Grb14) proteins; The Grb family binds to the epidermal growth factor receptor (EGFR, erbB1) via their SH2 domains. Grb14 is part of the Grb7 family of proteins which also includes Grb7, and Grb14. They are composed of an N-terminal Proline-rich domain, a Ras Associating-like (RA) domain, a Pleckstrin Homology (PH) domain, a phosphotyrosine interaction region (PIR, BPS) and a C-terminal SH2 domain. The SH2 domains of Grb7, Grb10 and Grb14 preferentially bind to a different RTK. Grb14 binds to Fibroblast Growth Factor Receptor (FGFR) and weakly to the erbB2 receptor. 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: 198277  Cd Length: 108  Bit Score: 48.77  E-value: 6.94e-07
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568918593  91 LHTHPIWLQLSLSEEEAAEVLQAQPP--GIFLVRKS-SKMQKKVLSLrlpcEFGAPLKEFTI----KESTYTFSLEGSGI 163
Cdd:cd10414    1 IHRSQPWFHHKISRDEAQRLIIQQGLvdGVFLVRDSqSNPRTFVLSM----SHGQKIKHFQIipveDDGELFHTLDDGHT 76

                         90       100
                 ....*....|....*....|....
gi 568918593 164 SFADLFRLIAFYCISRDVLPFTLK 187
Cdd:cd10414   77 RFTDLIQLVEFYQLNKGVLPCKLK 100
SH2_Grb7 cd10413
Src homology 2 (SH2) domain found in the growth factor receptor bound, subclass 7 (Grb7) ...
 91-187 8.73e-06

Src homology 2 (SH2) domain found in the growth factor receptor bound, subclass 7 (Grb7) proteins; The Grb family binds to the epidermal growth factor receptor (EGFR, erbB1) via their SH2 domains. Grb7 is part of the Grb7 family of proteins which also includes Grb10, and Grb14. They are composed of an N-terminal Proline-rich domain, a Ras Associating-like (RA) domain, a Pleckstrin Homology (PH) domain, a phosphotyrosine interaction region (PIR, BPS) and a C-terminal SH2 domain. The SH2 domains of Grb7, Grb10 and Grb14 preferentially bind to a different RTK. Grb7 binds strongly to the erbB2 receptor, unlike Grb10 and Grb14 which bind weakly to it. Grb7 family proteins are phosphorylated on serine/threonine as well as tyrosine residues. In general SH2 domains are involved in signal transduction. They typically bind pTyr-containing ligands via two surface pockets, a pTyr and hydrophobic binding pocket, allowing proteins with SH2 domains to localize to tyrosine phosphorylated sites.


Pssm-ID: 198276  Cd Length: 108  Bit Score: 45.28  E-value: 8.73e-06
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568918593  91 LHTHPIWLQLSLSEEEAAEVL--QAQPPGIFLVRKSSK-----------MQKKVLSLRLPCEfgaplkeftiKESTYTFS 157
Cdd:cd10413    1 IHRTQPWFHGRISREESQRLIgqQGLVDGVFLVRESQRnpqgfvlslchLQKVKHYLILPSE----------EEGRLYFS 70

                         90       100       110
                 ....*....|....*....|....*....|
gi 568918593 158 LEGSGISFADLFRLIAFYCISRDVLPFTLK 187
Cdd:cd10413   71 MDDGQTRFTDLLQLVEFHQLNRGILPCLLR 100
SH2_Grb10 cd10415
Src homology 2 (SH2) domain found in the growth factor receptor bound, subclass 10 (Grb10) ...
 91-189 1.27e-05

Src homology 2 (SH2) domain found in the growth factor receptor bound, subclass 10 (Grb10) proteins; The Grb family binds to the epidermal growth factor receptor (EGFR, erbB1) via their SH2 domains. Grb10 is part of the Grb7 family of proteins which also includes Grb7, and Grb14. They are composed of an N-terminal Proline-rich domain, a Ras Associating-like (RA) domain, a Pleckstrin Homology (PH) domain, a phosphotyrosine interaction region (PIR, BPS) and a C-terminal SH2 domain. The SH2 domains of Grb7, Grb10 and Grb14 preferentially bind to a different RTK. Grb10 has been shown to interact with many different proteins, including the insulin and IGF1 receptors, platelet-derived growth factor (PDGF) receptor-beta, Ret, Kit, Raf1 and MEK1, and Nedd4. 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: 198278  Cd Length: 108  Bit Score: 45.01  E-value: 1.27e-05
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568918593  91 LHTHPIWLQLSLSEEEAAEVL--QAQPPGIFLVRKSSKMQKK-VLSLrlpCEFgAPLKEFTI----KESTYTFSLEGSGI 163
Cdd:cd10415    1 IHRTQHWFHGRISREESHRIIkqQGLVDGLFLLRDSQSNPKAfVLTL---CHH-QKIKNFQIlpceDDGQTFFSLDDGNT 76

                         90       100
                 ....*....|....*....|....*.
gi 568918593 164 SFADLFRLIAFYCISRDVLPFTLKLP 189
Cdd:cd10415   77 KFSDLIQLVDFYQLNKGVLPCKLKHH 102
SH2 smart00252
Src homology 2 domains; Src homology 2 domains bind phosphotyrosine-containing polypeptides ...
 102-175 5.64e-05

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: 42.22  E-value: 5.64e-05
                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 568918593   102 LSEEEAAEVLQAQPPGIFLVRKSSKMQKK-VLSLRlpceFGAPLKEFTIKESTY-TFSLEGsGISFADLFRLIAFY 175
Cdd:smart00252   8 ISREEAEKLLKNEGDGDFLVRDSESSPGDyVLSVR----VKGKVKHYRIRRNEDgKFYLEG-GRKFPSLVELVEHY 78
SH2_SOCS1 cd10382
Src homology 2 (SH2) domain found in suppressor of cytokine signaling (SOCS) proteins; SH2 ...
 102-178 1.26e-04

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


Pssm-ID: 198245  Cd Length: 98  Bit Score: 41.96  E-value: 1.26e-04
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568918593 102 LSEEEAAEVLQAQPPGIFLVRKSSkmQKKV---LSLRLPcefGAPLkEFTIKESTYTFSLEGSGISFADLFRLIAFYCIS 178
Cdd:cd10382   17 LSVEEAHAKLKREPVGTFLIRDSR--QKNCffaLSVKMA---SGPV-SIRILFKAGKFSLDGSKESFDCLFKLLEHYVAS 90
SH2_SH2D4B cd10351
Src homology 2 domain found in the SH2 domain containing protein 4B (SH2D4B); SH2D4B contains ...
 97-160 5.98e-03

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


Pssm-ID: 198214  Cd Length: 103  Bit Score: 37.18  E-value: 5.98e-03
                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|....
gi 568918593  97 WLQLSLSEEEAAEVLQAQPPGIFLVRKSSKMQKKVLSLRLPCEFgaplKEFTIKESTYTFSLEG 160
Cdd:cd10351    9 WFHGIISREEAEALLMNATEGSFLVRVSEKIWGYTLSYRLQSGF----KHFLVDASGDFYSFLG 68
 
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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