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Conserved domains on  [gi|193207473|ref|NP_001122880|]
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SH2 domain-containing protein [Caenorhabditis elegans]

Protein Classification

Graphical summary

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List of domain hits

 Name Accession Description Interval E-value
RA_Rin cd01776
Ras-associating (RA) domain of Ras and Rab interactor (Rin) protein family; Family of ...
 1791-1879 6.46e-33

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: 123.17  E-value: 6.46e-33
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 193207473 1791 DAFVKIAVPDEAVGCVRYATFPGVPMLTTSKLSRLVAHQQGITNPEEHGLYLIAEGFESCLSPSECPVLVHEQLK-KDKK 1869
Cdd:cd01776     1 QGFLRVAVPDENNGSIVSKTLPVRPSMTAREVCKMIAHKFRVTNPQDYGLFLLVDGEEIQLEDNECPQLIKGELLaTSKK 80

                          90
                  ....*....|
gi 193207473 1870 PHMFAYKRHE 1879
Cdd:cd01776    81 PCYFAYKRID 90
SH2 super family cl15255
Src homology 2 (SH2) domain; In general, SH2 domains are involved in signal transduction; they ...
 376-489 2.64e-13

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 cd10393:

Pssm-ID: 472789  Cd Length: 101  Bit Score: 67.57  E-value: 2.64e-13
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 193207473  376 LLEQIIRTHAVWYLPHMGRPEVLHLLRRMEPGNFIVRASTRENCMALSVRL--APGAHVEIDHYIIEklvvplkpttske 453
Cdd:cd10393     1 LRERLLLTRPVWLQLRANAAAALHVLRTEPPGTFLVRKSNTRQCQALCVRLpeASGPSFVSSHYIQE------------- 67

                          90       100       110
                  ....*....|....*....|....*....|....*.
gi 193207473  454 paaptTAKAVRLEGSPLTFRSLPLLIEHYCVNEDEL 489
Cdd:cd10393    68 -----SPGGVSLEGSELTFPDLVQLICAYCHTRDIL 98
VPS9 super family cl19569
Vacuolar sorting protein 9 (VPS9) domain; This domain acts as a GDP-GTP exchange factor (GEF). ...
 1624-1738 4.57e-05

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.


The actual alignment was detected with superfamily member pfam02204:

Pssm-ID: 473191  Cd Length: 104  Bit Score: 44.12  E-value: 4.57e-05
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 193207473  1624 MEQVKLLMRKMQNHYSPMKKLENLMKAVGLVLGCqVNNGNENEnptdPMSCgyrglppgDDLVRWFVYILSRTSTVGCEV 1703
Cdd:pfam02204    1 WEQAQQELKKLNEAKSPREKLKCLLRTCKLITEA-LSKSNRDE----SLGA--------DDLLPILIYVLIRANPPNLYS 67

                           90       100       110
                   ....*....|....*....|....*....|....*
gi 193207473  1704 EAWYMWELLpQPIVTQSDASYYLTSLWSAVHVLKS 1738
Cdd:pfam02204   68 NLQFISEFR-DPDLLSGEEGYYLTTLEAALEFIES 101
 
Name Accession Description Interval E-value
RA_Rin cd01776
Ras-associating (RA) domain of Ras and Rab interactor (Rin) protein family; Family of ...
 1791-1879 6.46e-33

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: 123.17  E-value: 6.46e-33
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 193207473 1791 DAFVKIAVPDEAVGCVRYATFPGVPMLTTSKLSRLVAHQQGITNPEEHGLYLIAEGFESCLSPSECPVLVHEQLK-KDKK 1869
Cdd:cd01776     1 QGFLRVAVPDENNGSIVSKTLPVRPSMTAREVCKMIAHKFRVTNPQDYGLFLLVDGEEIQLEDNECPQLIKGELLaTSKK 80

                          90
                  ....*....|
gi 193207473 1870 PHMFAYKRHE 1879
Cdd:cd01776    81 PCYFAYKRID 90
SH2_RIN1 cd10393
Src homology 2 (SH2) domain found in Ras and Rab interactor 1 (RIN1)-like proteins; RIN1, a ...
 376-489 2.64e-13

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: 67.57  E-value: 2.64e-13
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 193207473  376 LLEQIIRTHAVWYLPHMGRPEVLHLLRRMEPGNFIVRASTRENCMALSVRL--APGAHVEIDHYIIEklvvplkpttske 453
Cdd:cd10393     1 LRERLLLTRPVWLQLRANAAAALHVLRTEPPGTFLVRKSNTRQCQALCVRLpeASGPSFVSSHYIQE------------- 67

                          90       100       110
                  ....*....|....*....|....*....|....*.
gi 193207473  454 paaptTAKAVRLEGSPLTFRSLPLLIEHYCVNEDEL 489
Cdd:cd10393    68 -----SPGGVSLEGSELTFPDLVQLICAYCHTRDIL 98
SH2 smart00252
Src homology 2 domains; Src homology 2 domains bind phosphotyrosine-containing polypeptides ...
 387-487 2.02e-11

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: 61.48  E-value: 2.02e-11
                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 193207473    387 WYLPHMGRPEVLHLLRRMEPGNFIVRASTRE-NCMALSVRlapgAHVEIDHYIIEklvvplkpttskepaaPTTAKAVRL 465
Cdd:smart00252    3 WYHGFISREEAEKLLKNEGDGDFLVRDSESSpGDYVLSVR----VKGKVKHYRIR----------------RNEDGKFYL 62

                            90       100
                    ....*....|....*....|..
gi 193207473    466 EGsPLTFRSLPLLIEHYCVNED 487
Cdd:smart00252   63 EG-GRKFPSLVELVEHYQKNSL 83
SH2 pfam00017
SH2 domain;
387-482 9.36e-08

SH2 domain;


Pssm-ID: 425423 [Multi-domain]  Cd Length: 77  Bit Score: 51.06  E-value: 9.36e-08
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 193207473   387 WYLPHMGRPEVLHLLR-RMEPGNFIVRASTRE-NCMALSVRLapGAHVEidHYIIEKLvvplkpttskepaapTTAKAVR 464
Cdd:pfam00017    1 WYHGKISRQEAERLLLnGKPDGTFLVRESESTpGGYTLSVRD--DGKVK--HYKIQST---------------DNGGYYI 61

                           90
                   ....*....|....*...
gi 193207473   465 LEGspLTFRSLPLLIEHY 482
Cdd:pfam00017   62 SGG--VKFSSLAELVEHY 77
VPS9 pfam02204
Vacuolar sorting protein 9 (VPS9) domain; This domain acts as a GDP-GTP exchange factor (GEF). ...
 1624-1738 4.57e-05

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: 44.12  E-value: 4.57e-05
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 193207473  1624 MEQVKLLMRKMQNHYSPMKKLENLMKAVGLVLGCqVNNGNENEnptdPMSCgyrglppgDDLVRWFVYILSRTSTVGCEV 1703
Cdd:pfam02204    1 WEQAQQELKKLNEAKSPREKLKCLLRTCKLITEA-LSKSNRDE----SLGA--------DDLLPILIYVLIRANPPNLYS 67

                           90       100       110
                   ....*....|....*....|....*....|....*
gi 193207473  1704 EAWYMWELLpQPIVTQSDASYYLTSLWSAVHVLKS 1738
Cdd:pfam02204   68 NLQFISEFR-DPDLLSGEEGYYLTTLEAALEFIES 101
 
Name Accession Description Interval E-value
RA_Rin cd01776
Ras-associating (RA) domain of Ras and Rab interactor (Rin) protein family; Family of ...
 1791-1879 6.46e-33

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: 123.17  E-value: 6.46e-33
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 193207473 1791 DAFVKIAVPDEAVGCVRYATFPGVPMLTTSKLSRLVAHQQGITNPEEHGLYLIAEGFESCLSPSECPVLVHEQLK-KDKK 1869
Cdd:cd01776     1 QGFLRVAVPDENNGSIVSKTLPVRPSMTAREVCKMIAHKFRVTNPQDYGLFLLVDGEEIQLEDNECPQLIKGELLaTSKK 80

                          90
                  ....*....|
gi 193207473 1870 PHMFAYKRHE 1879
Cdd:cd01776    81 PCYFAYKRID 90
SH2_RIN1 cd10393
Src homology 2 (SH2) domain found in Ras and Rab interactor 1 (RIN1)-like proteins; RIN1, a ...
 376-489 2.64e-13

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: 67.57  E-value: 2.64e-13
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 193207473  376 LLEQIIRTHAVWYLPHMGRPEVLHLLRRMEPGNFIVRASTRENCMALSVRL--APGAHVEIDHYIIEklvvplkpttske 453
Cdd:cd10393     1 LRERLLLTRPVWLQLRANAAAALHVLRTEPPGTFLVRKSNTRQCQALCVRLpeASGPSFVSSHYIQE------------- 67

                          90       100       110
                  ....*....|....*....|....*....|....*.
gi 193207473  454 paaptTAKAVRLEGSPLTFRSLPLLIEHYCVNEDEL 489
Cdd:cd10393    68 -----SPGGVSLEGSELTFPDLVQLICAYCHTRDIL 98
SH2 cd00173
Src homology 2 (SH2) domain; In general, SH2 domains are involved in signal transduction; they ...
 387-482 1.46e-12

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: 64.78  E-value: 1.46e-12
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 193207473  387 WYLPHMGRPEVLHLLRRMEPGNFIVRASTRE-NCMALSVRLAPGahvEIDHYIIEKlvvplkpttskepaapTTAKAVRL 465
Cdd:cd00173     2 WFHGSISREEAERLLRGKPDGTFLVRESSSEpGDYVLSVRSGDG---KVKHYLIER----------------NEGGYYLL 62

                          90
                  ....*....|....*..
gi 193207473  466 EGSPLTFRSLPLLIEHY 482
Cdd:cd00173    63 GGSGRTFPSLPELVEHY 79
SH2_RIN_family cd10339
Src homology 2 (SH2) domain found in Ras and Rab interactor (RIN)-family; The RIN (AKA Ras ...
 376-489 8.18e-12

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: 63.32  E-value: 8.18e-12
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 193207473  376 LLEQIIRTHAVWYLPHMGRPEVLHLLRRMEPGNFIVRASTRENCMALSVRL--APGAHVEIDHYIIEklvvplkpttskE 453
Cdd:cd10339     1 LLERLLLTRPVWLQLQLNAAEAAHMLQTEPPGTFLVRKSNTRQCQVLCMRLpeASGPAFVSEHYIKE------------S 68

                          90       100       110
                  ....*....|....*....|....*....|....*.
gi 193207473  454 PAapttakAVRLEGSPLTFRSLPLLIEHYCVNEDEL 489
Cdd:cd10339    69 PG------GVSLEGSELMFPDLFRLIAFYCHSRDIL 98
SH2 smart00252
Src homology 2 domains; Src homology 2 domains bind phosphotyrosine-containing polypeptides ...
 387-487 2.02e-11

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: 61.48  E-value: 2.02e-11
                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 193207473    387 WYLPHMGRPEVLHLLRRMEPGNFIVRASTRE-NCMALSVRlapgAHVEIDHYIIEklvvplkpttskepaaPTTAKAVRL 465
Cdd:smart00252    3 WYHGFISREEAEKLLKNEGDGDFLVRDSESSpGDYVLSVR----VKGKVKHYRIR----------------RNEDGKFYL 62

                            90       100
                    ....*....|....*....|..
gi 193207473    466 EGsPLTFRSLPLLIEHYCVNED 487
Cdd:smart00252   63 EG-GRKFPSLVELVEHYQKNSL 83
SH2_RIN3 cd10395
Src homology 2 (SH2) domain found in Ras and Rab interactor 3 (RIN3)-like proteins; RIN3, a ...
 376-489 1.19e-08

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: 54.39  E-value: 1.19e-08
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 193207473  376 LLEQIIRTHAVWYLPHMGRPEVLHLLRRMEPGNFIVRASTRENCMALSVRL-APGAHVEIDHYIIeklvvplkpttsKEP 454
Cdd:cd10395     1 ILEKLIKTCPVWLQLGMNQAEAARILHKEVAGMFLVRRDSNSKQMVLCVHFpSNESSAEVLEYPI------------KEE 68

                          90       100       110
                  ....*....|....*....|....*....|....*
gi 193207473  455 AApttakAVRLEGSPLTFRSLPLLIEHYCVNEDEL 489
Cdd:cd10395    69 KS-----ILYLEGSVLVFEDIFKLIAFYCVSRDLL 98
SH2 pfam00017
SH2 domain;
387-482 9.36e-08

SH2 domain;


Pssm-ID: 425423 [Multi-domain]  Cd Length: 77  Bit Score: 51.06  E-value: 9.36e-08
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 193207473   387 WYLPHMGRPEVLHLLR-RMEPGNFIVRASTRE-NCMALSVRLapGAHVEidHYIIEKLvvplkpttskepaapTTAKAVR 464
Cdd:pfam00017    1 WYHGKISRQEAERLLLnGKPDGTFLVRESESTpGGYTLSVRD--DGKVK--HYKIQST---------------DNGGYYI 61

                           90
                   ....*....|....*...
gi 193207473   465 LEGspLTFRSLPLLIEHY 482
Cdd:pfam00017   62 SGG--VKFSSLAELVEHY 77
SH2_RIN2 cd10394
Src homology 2 (SH2) domain found in Ras and Rab interactor 2 (RIN2)-like proteins; RIN2, a ...
 376-489 1.85e-07

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: 50.97  E-value: 1.85e-07
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 193207473  376 LLEQIIRTHAVWYLPHMGRPEVLHLLRRMEPGNFIVRASTRENCMALSVRL--APGAHVeidhyiiekLVVPLKPTTSke 453
Cdd:cd10394     1 ILDRLLHTHPIWLQLSLSEEEAAEVLQAQPPGIFLVRKSSKMQKKVLSLRLpcEFGAPL---------KEFAIKESTY-- 69

                          90       100       110
                  ....*....|....*....|....*....|....*.
gi 193207473  454 paapttakAVRLEGSPLTFRSLPLLIEHYCVNEDEL 489
Cdd:cd10394    70 --------TFSLEGSGISFADLFRLIAFYCISRDVL 97
SH2_Tensin_like cd09927
Src homology 2 domain found in Tensin-like proteins; SH2 domain found in Tensin-like proteins. ...
 383-497 4.00e-07

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


Pssm-ID: 198181 [Multi-domain]  Cd Length: 116  Bit Score: 50.50  E-value: 4.00e-07
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 193207473  383 THAVWYLPHMGRPEVLHLLRRMEPGNFIVRAS-TRENCMALSVRLA---PGAHVE----------IDHYIIEklvvplkp 448
Cdd:cd09927     1 TSKYWYKPNISRDQAIALLKDKPPGTFLVRDStTYKGAYGLAVKVAtppPGVNPFeakgdpeselVRHFLIE-------- 72

                          90       100       110       120       130
                  ....*....|....*....|....*....|....*....|....*....|.
gi 193207473  449 ttskepaapTTAKAVRLEGSP--LTFRSLPLLIEHYCVNEDELEHRLQLPS 497
Cdd:cd09927    73 ---------PSPKGVKLKGCPnePVFGSLSALVYQHSITPLALPCKLRIPD 114
VPS9 pfam02204
Vacuolar sorting protein 9 (VPS9) domain; This domain acts as a GDP-GTP exchange factor (GEF). ...
 1624-1738 4.57e-05

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: 44.12  E-value: 4.57e-05
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 193207473  1624 MEQVKLLMRKMQNHYSPMKKLENLMKAVGLVLGCqVNNGNENEnptdPMSCgyrglppgDDLVRWFVYILSRTSTVGCEV 1703
Cdd:pfam02204    1 WEQAQQELKKLNEAKSPREKLKCLLRTCKLITEA-LSKSNRDE----SLGA--------DDLLPILIYVLIRANPPNLYS 67

                           90       100       110
                   ....*....|....*....|....*....|....*
gi 193207473  1704 EAWYMWELLpQPIVTQSDASYYLTSLWSAVHVLKS 1738
Cdd:pfam02204   68 NLQFISEFR-DPDLLSGEEGYYLTTLEAALEFIES 101
SH2_C-SH2_PLC_gamma_like cd09932
C-terminal Src homology 2 (C-SH2) domain in Phospholipase C gamma; Phospholipase C gamma is a ...
 387-441 2.26e-03

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: 39.56  E-value: 2.26e-03
                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....*..
gi 193207473  387 WYLPHMGRPEVLHLLRRM-EPGNFIVRASTRE-NCMALSVRlapgAHVEIDHYIIEK 441
Cdd:cd09932     6 WFHANLTREQAEEMLMRVpRDGAFLVRPSETDpNSFAISFR----AEGKIKHCRIKQ 58
RA_Rin2 cd16131
Ras-associating (RA) domain found in Ras and Rab interactor 2 (Rin2); Rin2, also termed Ras ...
 1793-1877 2.91e-03

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: 38.69  E-value: 2.91e-03
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 193207473 1793 FVKIAVPDEAVGCVRyATFPGVPMLTTSKLSRLVAHQQGITNPEEHGLYLIAEGFESCLSPSECPVLVHEQLKKDKKPHM 1872
Cdd:cd16131     4 YLRVAFQEVNSGCTA-KTLLVRPYTTTEEVCQLCAQKFKVQDPENYSLFLLIDDTWQQLAEDTYPQKIKAELHSRPQPQI 82


                  ....*..
gi 193207473 1873 --FAYKR 1877
Cdd:cd16131    83 fhFVYKR 89
 
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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