NCBI Conserved Domain Search

Conserved domains on [gi|1958643426|ref|XP_038960165|]

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ras and Rab interactor-like protein isoform X4 [Rattus norvegicus]

Protein Classification

VPS9 domain-containing protein; SH2 domain-containing protein( domain architecture ID 10332974)

VPS9 domain-containing protein similar to Homo sapiens VPS9 domain-containing protein 1 that regulates tubular endosome formation through specific activation of Rab22A| SH2 (Src homology 2) domain-containing protein may act as an intracellular signal-transducing protein

Graphical summary

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List of domain hits

Name

Accession

Description

Interval

E-value

VPS9

pfam02204

Vacuolar sorting protein 9 (VPS9) domain; This domain acts as a GDP-GTP exchange factor (GEF). ...

417-519

5.06e-27

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: 104.99 E-value: 5.06e-27

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958643426 417 RIHARLAHLHAACAPRRKVALLLAVCSDVYAGLAGGENKEPLGADAFLPALTEELIWSPhIGETQLDVEFLMELLDPGEL 496
Cdd:pfam02204   3 QAQQELKKLNEAKSPREKLKCLLRTCKLITEALSKSNRDESLGADDLLPILIYVLIRAN-PPNLYSNLQFISEFRDPDLL 81

                          90       100
                  ....*....|....*....|...
gi 1958643426 497 RGEAGYYLTTWFGALYHIAHYQP 519
Cdd:pfam02204  82 SGEEGYYLTTLEAALEFIESLDP 104

SH2 super family

cl15255

Src homology 2 (SH2) domain; In general, SH2 domains are involved in signal transduction; they ...

43-136

1.34e-09

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: 55.63 E-value: 1.34e-09

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958643426  43 RLQRTQRVWQVPELDAEHAKAFLKPWPLGSFLVIGQDPDQVLML------KTGPSSgdINTYQIQKFPGGVSLESSNLCM 116
Cdd:cd10393     4 RLLLTRPVWLQLRANAAAALHVLRTEPPGTFLVRKSNTRQCQALcvrlpeASGPSF--VSSHYIQESPGGVSLEGSELTF 81

                          90       100
                  ....*....|....*....|
gi 1958643426 117 PDFPHLLAFLSASRDVLPRT 136
Cdd:cd10393    82 PDLVQLICAYCHTRDILLLP 101

Name

Accession

Description

Interval

E-value

VPS9

pfam02204

Vacuolar sorting protein 9 (VPS9) domain; This domain acts as a GDP-GTP exchange factor (GEF). ...

417-519

5.06e-27

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: 104.99 E-value: 5.06e-27

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958643426 417 RIHARLAHLHAACAPRRKVALLLAVCSDVYAGLAGGENKEPLGADAFLPALTEELIWSPhIGETQLDVEFLMELLDPGEL 496
Cdd:pfam02204   3 QAQQELKKLNEAKSPREKLKCLLRTCKLITEALSKSNRDESLGADDLLPILIYVLIRAN-PPNLYSNLQFISEFRDPDLL 81

                          90       100
                  ....*....|....*....|...
gi 1958643426 497 RGEAGYYLTTWFGALYHIAHYQP 519
Cdd:pfam02204  82 SGEEGYYLTTLEAALEFIESLDP 104

VPS9

smart00167

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

420-514

8.47e-10

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

Pssm-ID: 128469 Cd Length: 117 Bit Score: 56.69 E-value: 8.47e-10

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958643426  420 ARLAHLHAACAPRRKVALLLAVCSDVYAGLAGGENkEPLGADAFLPALTEELIwSPHIGETQLDVEFLMELLDPGELRGE 499
Cdd:smart00167   7 IELKFLQLYKSPSDKIKCLLRACKLIYTLLETQSG-EVAGADDFLPVLIYVII-KCDPRDLLLNAEYMEEFLEPSLLTGE 84

                           90
                   ....*....|....*
gi 1958643426  500 AGYYLTTWFGALYHI 514
Cdd:smart00167  85 GGYYLTSLSAALALI 99

SH2_RIN1

cd10393

Src homology 2 (SH2) domain found in Ras and Rab interactor 1 (RIN1)-like proteins; RIN1, a ...

43-136

1.34e-09

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: 55.63 E-value: 1.34e-09

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958643426  43 RLQRTQRVWQVPELDAEHAKAFLKPWPLGSFLVIGQDPDQVLML------KTGPSSgdINTYQIQKFPGGVSLESSNLCM 116
Cdd:cd10393     4 RLLLTRPVWLQLRANAAAALHVLRTEPPGTFLVRKSNTRQCQALcvrlpeASGPSF--VSSHYIQESPGGVSLEGSELTF 81

                          90       100
                  ....*....|....*....|
gi 1958643426 117 PDFPHLLAFLSASRDVLPRT 136
Cdd:cd10393    82 PDLVQLICAYCHTRDILLLP 101

Name

Accession

Description

Interval

E-value

VPS9

pfam02204

Vacuolar sorting protein 9 (VPS9) domain; This domain acts as a GDP-GTP exchange factor (GEF). ...

417-519

5.06e-27

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: 104.99 E-value: 5.06e-27

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958643426 417 RIHARLAHLHAACAPRRKVALLLAVCSDVYAGLAGGENKEPLGADAFLPALTEELIWSPhIGETQLDVEFLMELLDPGEL 496
Cdd:pfam02204   3 QAQQELKKLNEAKSPREKLKCLLRTCKLITEALSKSNRDESLGADDLLPILIYVLIRAN-PPNLYSNLQFISEFRDPDLL 81

                          90       100
                  ....*....|....*....|...
gi 1958643426 497 RGEAGYYLTTWFGALYHIAHYQP 519
Cdd:pfam02204  82 SGEEGYYLTTLEAALEFIESLDP 104

VPS9

smart00167

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

420-514

8.47e-10

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

Pssm-ID: 128469 Cd Length: 117 Bit Score: 56.69 E-value: 8.47e-10

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958643426  420 ARLAHLHAACAPRRKVALLLAVCSDVYAGLAGGENkEPLGADAFLPALTEELIwSPHIGETQLDVEFLMELLDPGELRGE 499
Cdd:smart00167   7 IELKFLQLYKSPSDKIKCLLRACKLIYTLLETQSG-EVAGADDFLPVLIYVII-KCDPRDLLLNAEYMEEFLEPSLLTGE 84

                           90
                   ....*....|....*
gi 1958643426  500 AGYYLTTWFGALYHI 514
Cdd:smart00167  85 GGYYLTSLSAALALI 99

SH2_RIN1

cd10393

Src homology 2 (SH2) domain found in Ras and Rab interactor 1 (RIN1)-like proteins; RIN1, a ...

43-136

1.34e-09

Pssm-ID: 198256 Cd Length: 101 Bit Score: 55.63 E-value: 1.34e-09

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958643426  43 RLQRTQRVWQVPELDAEHAKAFLKPWPLGSFLVIGQDPDQVLML------KTGPSSgdINTYQIQKFPGGVSLESSNLCM 116
Cdd:cd10393     4 RLLLTRPVWLQLRANAAAALHVLRTEPPGTFLVRKSNTRQCQALcvrlpeASGPSF--VSSHYIQESPGGVSLEGSELTF 81

                          90       100
                  ....*....|....*....|
gi 1958643426 117 PDFPHLLAFLSASRDVLPRT 136
Cdd:cd10393    82 PDLVQLICAYCHTRDILLLP 101

SH2_RIN_family

cd10339

Src homology 2 (SH2) domain found in Ras and Rab interactor (RIN)-family; The RIN (AKA Ras ...

43-136

1.17e-08

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: 52.92 E-value: 1.17e-08

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958643426  43 RLQRTQRVWQVPELDAEHAKAFLKPWPLGSFLVIGQDPDQVLML----KTGPSSGDINTYQIQKFPGGVSLESSNLCMPD 118
Cdd:cd10339     4 RLLLTRPVWLQLQLNAAEAAHMLQTEPPGTFLVRKSNTRQCQVLcmrlPEASGPAFVSEHYIKESPGGVSLEGSELMFPD 83

                          90
                  ....*....|....*...
gi 1958643426 119 FPHLLAFLSASRDVLPRT 136
Cdd:cd10339    84 LFRLIAFYCHSRDILPFT 101

SH2_RIN2

cd10394

Src homology 2 (SH2) domain found in Ras and Rab interactor 2 (RIN2)-like proteins; RIN2, a ...

41-136

6.58e-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: 47.88 E-value: 6.58e-07

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958643426  41 LLRLQRTQRVWQVPELDAEHAKAFLKPWPLGSFLVIGQDPDQ--VLMLKTGPSSGDI-NTYQIQKFPGGVSLESSNLCMP 117
Cdd:cd10394     2 LDRLLHTHPIWLQLSLSEEEAAEVLQAQPPGIFLVRKSSKMQkkVLSLRLPCEFGAPlKEFAIKESTYTFSLEGSGISFA 81

                          90
                  ....*....|....*....
gi 1958643426 118 DFPHLLAFLSASRDVLPRT 136
Cdd:cd10394    82 DLFRLIAFYCISRDVLPFT 100

SH2_RIN3

cd10395

Src homology 2 (SH2) domain found in Ras and Rab interactor 3 (RIN3)-like proteins; RIN3, a ...

41-136

2.22e-03

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: 37.83 E-value: 2.22e-03

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958643426  41 LLRLQRTQRVWQVPELDAEHAKAFLKPWPLGSFLVIgQDPDQVLM-----LKTGPSSGDINTYQIQKFPGGVSLESSNLC 115
Cdd:cd10395     2 LEKLIKTCPVWLQLGMNQAEAARILHKEVAGMFLVR-RDSNSKQMvlcvhFPSNESSAEVLEYPIKEEKSILYLEGSVLV 80

                          90       100
                  ....*....|....*....|.
gi 1958643426 116 MPDFPHLLAFLSASRDVLPRT 136
Cdd:cd10395    81 FEDIFKLIAFYCVSRDLLPFT 101

SH2_Tensin_like

cd09927

Src homology 2 domain found in Tensin-like proteins; SH2 domain found in Tensin-like proteins. ...

47-141

5.87e-03

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: 37.02 E-value: 5.87e-03

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958643426  47 TQRVWQVPELDAEHAKAFLKPWPLGSFLV---------------IGQDPDQVLM--LKTGPSSGDINTYQIQKFPGGVSL 109
Cdd:cd09927     1 TSKYWYKPNISRDQAIALLKDKPPGTFLVrdsttykgayglavkVATPPPGVNPfeAKGDPESELVRHFLIEPSPKGVKL 80

                          90       100       110
                  ....*....|....*....|....*....|....*
gi 1958643426 110 ESSNlCMPDFPHLLAFL---SASRDVLPRTLLLPT 141
Cdd:cd09927    81 KGCP-NEPVFGSLSALVyqhSITPLALPCKLRIPD 114

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