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Conserved domains on  [gi|768036912|ref|XP_011529078|]
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IQ motif and SEC7 domain-containing protein 2 isoform X12 [Homo sapiens]

Protein Classification

IQ motif and SEC7 domain-containing protein( domain architecture ID 11116401)

IQ motif and SEC7 domain-containing protein (IQSEC) contains an IQ domain that may bind calmodulin, a PH domain that may mediate membrane localization by binding of phosphoinositides, and a SEC7 domain that functions as a guanine-nucleotide-exchange factor (GEF) for members of the ARF class of small GTPases

Graphical summary

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List of domain hits

Name Accession Description Interval E-value
Sec7 pfam01369
Sec7 domain; The Sec7 domain is a guanine-nucleotide-exchange-factor (GEF) for the pfam00025 ...
785-973 1.10e-88

Sec7 domain; The Sec7 domain is a guanine-nucleotide-exchange-factor (GEF) for the pfam00025 family.


:

Pssm-ID: 460178  Cd Length: 183  Bit Score: 283.20  E-value: 1.10e-88
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 768036912   785 QRRHYRIGLNLFNKKPEKGIQYLIERGFLSDTPVGVAHFILERKGLSRQMIGEFLGNRqKQFNRDVLDCVVDEMDFSSMD 864
Cdd:pfam01369    1 RKKLLREGIEKFNKKPKKGIEYLIEKGFIEDDPESIAKFLFETPGLDKKAIGEYLGKP-DEFNIEVLKAFVDLFDFKGLR 79
                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 768036912   865 LDDALRKFQSHIRVQGEAQKVERLIEAFSQRYCVCNPalvRQFRNPDTIFILAFAIILLNTDMYSPSVKaeRKMKLDDFI 944
Cdd:pfam01369   80 IDEALRLFLESFRLPGEAQKIDRIMEAFAERYYEQNP---GVFANADAAYVLAYSIIMLNTDLHNPNVK--KKMTLEDFI 154
                          170       180
                   ....*....|....*....|....*....
gi 768036912   945 KNLRGVDNGEDIPRDLLVGIYQRIQGREL 973
Cdd:pfam01369  155 RNLRGINDGKDFPDEYLEEIYDSIKKNEI 183
IQ_SEC7_PH pfam16453
PH domain; This PH domain is found in IQ motif and SEC7 domain-containing proteins.
995-1124 1.95e-69

PH domain; This PH domain is found in IQ motif and SEC7 domain-containing proteins.


:

Pssm-ID: 465120  Cd Length: 127  Bit Score: 227.93  E-value: 1.95e-69
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 768036912   995 PVLSLPHRRLVCCCQLYEVPDPNRPQRLGLHQREVFLFNDLLVVTKIFQKKKILVTYSFRQSFPLVEMHMQLFQNSYYQF 1074
Cdd:pfam16453    1 PVLALPHRRLVCYCRLFEVPDPNKKQKLGLHQREVFLFNDLLVVTKIFSKKKSSVTYSFRQSFGLLGMQVSLFENSYYPH 80
                           90       100       110       120       130
                   ....*....|....*....|....*....|....*....|....*....|
gi 768036912  1075 GIKLLSAVpggERKVLIIFNAPSLQDRLRFTSDLRESIAEVQEMEKYRVE 1124
Cdd:pfam16453   81 GIRLTSRV---DSKVLITFNARNEHDRKKFVEDLRESIAEVQEMEKLRIE 127
 
Name Accession Description Interval E-value
Sec7 pfam01369
Sec7 domain; The Sec7 domain is a guanine-nucleotide-exchange-factor (GEF) for the pfam00025 ...
785-973 1.10e-88

Sec7 domain; The Sec7 domain is a guanine-nucleotide-exchange-factor (GEF) for the pfam00025 family.


Pssm-ID: 460178  Cd Length: 183  Bit Score: 283.20  E-value: 1.10e-88
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 768036912   785 QRRHYRIGLNLFNKKPEKGIQYLIERGFLSDTPVGVAHFILERKGLSRQMIGEFLGNRqKQFNRDVLDCVVDEMDFSSMD 864
Cdd:pfam01369    1 RKKLLREGIEKFNKKPKKGIEYLIEKGFIEDDPESIAKFLFETPGLDKKAIGEYLGKP-DEFNIEVLKAFVDLFDFKGLR 79
                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 768036912   865 LDDALRKFQSHIRVQGEAQKVERLIEAFSQRYCVCNPalvRQFRNPDTIFILAFAIILLNTDMYSPSVKaeRKMKLDDFI 944
Cdd:pfam01369   80 IDEALRLFLESFRLPGEAQKIDRIMEAFAERYYEQNP---GVFANADAAYVLAYSIIMLNTDLHNPNVK--KKMTLEDFI 154
                          170       180
                   ....*....|....*....|....*....
gi 768036912   945 KNLRGVDNGEDIPRDLLVGIYQRIQGREL 973
Cdd:pfam01369  155 RNLRGINDGKDFPDEYLEEIYDSIKKNEI 183
Sec7 cd00171
Sec7 domain; Domain named after the S. cerevisiae SEC7 gene product. The Sec7 domain is the ...
787-973 3.57e-79

Sec7 domain; Domain named after the S. cerevisiae SEC7 gene product. The Sec7 domain is the central domain of the guanine-nucleotide-exchange factors (GEFs) of the ADP-ribosylation factor family of small GTPases (ARFs) . It carries the exchange factor activity.


Pssm-ID: 238100  Cd Length: 185  Bit Score: 257.15  E-value: 3.57e-79
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 768036912  787 RHYRIGLNLFNKKPEKGIQYLIERGFL-SDTPVGVAHFILERKGLSRQMIGEFLGNRQkQFNRDVLDCVVDEMDFSSMDL 865
Cdd:cd00171     3 TLLSEGRQLFNRKPKKGISFLIEKGFLeDDSPKEIAKFLYETEGLNKKAIGEYLGENN-EFNSLVLHEFVDLFDFSGLRL 81
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 768036912  866 DDALRKFQSHIRVQGEAQKVERLIEAFSQRYCVCNPALVrqFRNPDTIFILAFAIILLNTDMYSPSVKaeRKMKLDDFIK 945
Cdd:cd00171    82 DEALRKFLQSFRLPGEAQKIDRLLEKFSERYCECNPGIF--SSSADAAYTLAYSIIMLNTDLHNPNVK--KKMTLEDFIK 157
                         170       180
                  ....*....|....*....|....*...
gi 768036912  946 NLRGVDNGEDIPRDLLVGIYQRIQGREL 973
Cdd:cd00171   158 NLRGINDGEDFPREFLKELYDSIKNNEI 185
Sec7 smart00222
Sec7 domain; Domain named after the S. cerevisiae SEC7 gene product, which is required for ...
785-973 9.73e-71

Sec7 domain; Domain named after the S. cerevisiae SEC7 gene product, which is required for proper protein transport through the Golgi. The domain facilitates guanine nucleotide exchange on the small GTPases, ARFs (ADP ribosylation factors).


Pssm-ID: 214569 [Multi-domain]  Cd Length: 189  Bit Score: 234.11  E-value: 9.73e-71
                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 768036912    785 QRRHYRIGLNLFNKKPEKGIQYLIERGFL-SDTPVGVAHFILERKGLSRQMIGEFLGNRqKQFNRDVLDCVVDEMDFSSM 863
Cdd:smart00222    4 RKKLLSEGIVKFNDKPKKGIQSLQEKGFLaNEDPQDVADFLSKNEGLNKKAIGDYLGEH-DEFNRLVLHAFVDLFDFSAK 82
                            90       100       110       120       130       140       150       160
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 768036912    864 DLDDALRKFQSHIRVQGEAQKVERLIEAFSQRYCVCNPALVRqFRNPDTIFILAFAIILLNTDMYSPSVKaeRKMKLDDF 943
Cdd:smart00222   83 DLDQALREFLESFRLPGEAQKIDRLLEAFSSRYCECNPGVFS-KANADAAYTLAYSLIMLNTDLHNPNVK--KKMTLEDF 159
                           170       180       190
                    ....*....|....*....|....*....|
gi 768036912    944 IKNLRGVDNGEDIPRDLLVGIYQRIQGREL 973
Cdd:smart00222  160 IKNVRGSNDGEDLPREFLEELYDSIKNNEI 189
IQ_SEC7_PH pfam16453
PH domain; This PH domain is found in IQ motif and SEC7 domain-containing proteins.
995-1124 1.95e-69

PH domain; This PH domain is found in IQ motif and SEC7 domain-containing proteins.


Pssm-ID: 465120  Cd Length: 127  Bit Score: 227.93  E-value: 1.95e-69
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 768036912   995 PVLSLPHRRLVCCCQLYEVPDPNRPQRLGLHQREVFLFNDLLVVTKIFQKKKILVTYSFRQSFPLVEMHMQLFQNSYYQF 1074
Cdd:pfam16453    1 PVLALPHRRLVCYCRLFEVPDPNKKQKLGLHQREVFLFNDLLVVTKIFSKKKSSVTYSFRQSFGLLGMQVSLFENSYYPH 80
                           90       100       110       120       130
                   ....*....|....*....|....*....|....*....|....*....|
gi 768036912  1075 GIKLLSAVpggERKVLIIFNAPSLQDRLRFTSDLRESIAEVQEMEKYRVE 1124
Cdd:pfam16453   81 GIRLTSRV---DSKVLITFNARNEHDRKKFVEDLRESIAEVQEMEKLRIE 127
PH_IQSEC cd13318
IQ motif and SEC7 domain-containing protein family Pleckstrin homology domain; The IQSEC (also ...
1000-1124 1.09e-61

IQ motif and SEC7 domain-containing protein family Pleckstrin homology domain; The IQSEC (also called BRAG/Brefeldin A-resistant Arf-gunanine nucleotide exchange factor) family are a subset of Arf GEFs that have been shown to activate Arf6, which acts in the endocytic pathway to control the trafficking of a subset of cargo proteins including integrins and have key roles in the function and organization of distinct excitatory and inhibitory synapses in the retina. The family consists of 3 members: IQSEC1 (also called BRAG2/GEP100), IQSEC2 (also called BRAG1), and IQSEC3 (also called SynArfGEF, BRAG3, or KIAA1110). IQSEC1 interacts with clathrin and modulates cell adhesion by regulating integrin surface expression and in addition to Arf6, it also activates the class II Arfs, Arf4 and Arf5. Mutations in IQSEC2 cause non-syndromic X-linked intellectual disability as well as reduced activation of Arf substrates (Arf1, Arf6). IQSEC3 regulates Arf6 at inhibitory synapses and associates with the dystrophin-associated glycoprotein complex and S-SCAM. These members contains a IQ domain that may bind calmodulin, a PH domain that is thought to mediate membrane localization by binding of phosphoinositides, and a SEC7 domain that can promote GEF activity on ARF. PH domains have diverse functions, but in general are involved in targeting proteins to the appropriate cellular location or in the interaction with a binding partner. They share little sequence conservation, but all have a common fold, which is electrostatically polarized. Less than 10% of PH domains bind phosphoinositide phosphates (PIPs) with high affinity and specificity. PH domains are distinguished from other PIP-binding domains by their specific high-affinity binding to PIPs with two vicinal phosphate groups: PtdIns(3,4)P2, PtdIns(4,5)P2 or PtdIns(3,4,5)P3 which results in targeting some PH domain proteins to the plasma membrane. A few display strong specificity in lipid binding. Any specificity is usually determined by loop regions or insertions in the N-terminus of the domain, which are not conserved across all PH domains. PH domains are found in cellular signaling proteins such as serine/threonine kinase, tyrosine kinases, regulators of G-proteins, endocytotic GTPases, adaptors, as well as cytoskeletal associated molecules and in lipid associated enzymes.


Pssm-ID: 270128  Cd Length: 128  Bit Score: 206.01  E-value: 1.09e-61
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 768036912 1000 PHRRLVCCCQLYEVPDPNRPQRLGLHQREVFLFNDLLVVTKIFQKKKILVTYSFRQSFPLVEMHMQLFQNSYYQFGIKLL 1079
Cdd:cd13318     1 PHRRLVCYCRLYEVPDPNKREKPGLHQREVFLFNDLLVVTKIFSKKKSSVTYSFRQSFSLLGMQVLLFETSHYPFGIRLT 80
                          90       100       110       120
                  ....*....|....*....|....*....|....*....|....*
gi 768036912 1080 SAVPGgerKVLIIFNAPSLQDRLRFTSDLRESIAEVQEMEKYRVE 1124
Cdd:cd13318    81 SPLDN---KVLITFNARNESDRKKFVEDLRESILEVNEMESLRIE 122
PLN03076 PLN03076
ARF guanine nucleotide exchange factor (ARF-GEF); Provisional
756-978 1.73e-49

ARF guanine nucleotide exchange factor (ARF-GEF); Provisional


Pssm-ID: 215560 [Multi-domain]  Cd Length: 1780  Bit Score: 192.73  E-value: 1.73e-49
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 768036912  756 PPATGLCKQTYQRETRHSwDSPAFNNDVV---QRRHYRI----GLNLFNKKPEKGIQYLIERGFLSDTPVGVAHFILERK 828
Cdd:PLN03076  581 PVANGNGDENGEGSDSHS-ELSSETSDAAtieQRRAYKLelqeGISLFNRKPKKGIEFLINANKVGESPEEIAAFLKDAS 659
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 768036912  829 GLSRQMIGEFLGNRQkQFNRDVLDCVVDEMDFSSMDLDDALRKFQSHIRVQGEAQKVERLIEAFSQRYCVCNPalvRQFR 908
Cdd:PLN03076  660 GLNKTLIGDYLGERE-DLSLKVMHAYVDSFDFQGMEFDEAIRAFLQGFRLPGEAQKIDRIMEKFAERYCKCNP---KAFS 735
                         170       180       190       200       210       220       230
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 768036912  909 NPDTIFILAFAIILLNTDMYSPSVKAerKMKLDDFIKNLRGVDNGEDIPRDLLVGIYQRIQGRELRTNDD 978
Cdd:PLN03076  736 SADTAYVLAYSVIMLNTDAHNPMVKN--KMSADDFIRNNRGIDDGKDLPEEFMRSLYERISKNEIKMKED 803
PH smart00233
Pleckstrin homology domain; Domain commonly found in eukaryotic signalling proteins. The ...
1004-1113 1.80e-03

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


Pssm-ID: 214574 [Multi-domain]  Cd Length: 102  Bit Score: 39.07  E-value: 1.80e-03
                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 768036912   1004 LVCCCQLYEVPDPNRPQRlglHQREVFLFNDLLVvtkIFQKKKILVTYSFRQSFPLVEMHMQL---FQNSYYQFGIKLLS 1080
Cdd:smart00233    1 VIKEGWLYKKSGGGKKSW---KKRYFVLFNSTLL---YYKSKKDKKSYKPKGSIDLSGCTVREapdPDSSKKPHCFEIKT 74
                            90       100       110
                    ....*....|....*....|....*....|...
gi 768036912   1081 AvpggeRKVLIIFNAPSLQDRLRFTSDLRESIA 1113
Cdd:smart00233   75 S-----DRKTLLLQAESEEEREKWVEALRKAIA 102
 
Name Accession Description Interval E-value
Sec7 pfam01369
Sec7 domain; The Sec7 domain is a guanine-nucleotide-exchange-factor (GEF) for the pfam00025 ...
785-973 1.10e-88

Sec7 domain; The Sec7 domain is a guanine-nucleotide-exchange-factor (GEF) for the pfam00025 family.


Pssm-ID: 460178  Cd Length: 183  Bit Score: 283.20  E-value: 1.10e-88
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 768036912   785 QRRHYRIGLNLFNKKPEKGIQYLIERGFLSDTPVGVAHFILERKGLSRQMIGEFLGNRqKQFNRDVLDCVVDEMDFSSMD 864
Cdd:pfam01369    1 RKKLLREGIEKFNKKPKKGIEYLIEKGFIEDDPESIAKFLFETPGLDKKAIGEYLGKP-DEFNIEVLKAFVDLFDFKGLR 79
                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 768036912   865 LDDALRKFQSHIRVQGEAQKVERLIEAFSQRYCVCNPalvRQFRNPDTIFILAFAIILLNTDMYSPSVKaeRKMKLDDFI 944
Cdd:pfam01369   80 IDEALRLFLESFRLPGEAQKIDRIMEAFAERYYEQNP---GVFANADAAYVLAYSIIMLNTDLHNPNVK--KKMTLEDFI 154
                          170       180
                   ....*....|....*....|....*....
gi 768036912   945 KNLRGVDNGEDIPRDLLVGIYQRIQGREL 973
Cdd:pfam01369  155 RNLRGINDGKDFPDEYLEEIYDSIKKNEI 183
Sec7 cd00171
Sec7 domain; Domain named after the S. cerevisiae SEC7 gene product. The Sec7 domain is the ...
787-973 3.57e-79

Sec7 domain; Domain named after the S. cerevisiae SEC7 gene product. The Sec7 domain is the central domain of the guanine-nucleotide-exchange factors (GEFs) of the ADP-ribosylation factor family of small GTPases (ARFs) . It carries the exchange factor activity.


Pssm-ID: 238100  Cd Length: 185  Bit Score: 257.15  E-value: 3.57e-79
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 768036912  787 RHYRIGLNLFNKKPEKGIQYLIERGFL-SDTPVGVAHFILERKGLSRQMIGEFLGNRQkQFNRDVLDCVVDEMDFSSMDL 865
Cdd:cd00171     3 TLLSEGRQLFNRKPKKGISFLIEKGFLeDDSPKEIAKFLYETEGLNKKAIGEYLGENN-EFNSLVLHEFVDLFDFSGLRL 81
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 768036912  866 DDALRKFQSHIRVQGEAQKVERLIEAFSQRYCVCNPALVrqFRNPDTIFILAFAIILLNTDMYSPSVKaeRKMKLDDFIK 945
Cdd:cd00171    82 DEALRKFLQSFRLPGEAQKIDRLLEKFSERYCECNPGIF--SSSADAAYTLAYSIIMLNTDLHNPNVK--KKMTLEDFIK 157
                         170       180
                  ....*....|....*....|....*...
gi 768036912  946 NLRGVDNGEDIPRDLLVGIYQRIQGREL 973
Cdd:cd00171   158 NLRGINDGEDFPREFLKELYDSIKNNEI 185
Sec7 smart00222
Sec7 domain; Domain named after the S. cerevisiae SEC7 gene product, which is required for ...
785-973 9.73e-71

Sec7 domain; Domain named after the S. cerevisiae SEC7 gene product, which is required for proper protein transport through the Golgi. The domain facilitates guanine nucleotide exchange on the small GTPases, ARFs (ADP ribosylation factors).


Pssm-ID: 214569 [Multi-domain]  Cd Length: 189  Bit Score: 234.11  E-value: 9.73e-71
                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 768036912    785 QRRHYRIGLNLFNKKPEKGIQYLIERGFL-SDTPVGVAHFILERKGLSRQMIGEFLGNRqKQFNRDVLDCVVDEMDFSSM 863
Cdd:smart00222    4 RKKLLSEGIVKFNDKPKKGIQSLQEKGFLaNEDPQDVADFLSKNEGLNKKAIGDYLGEH-DEFNRLVLHAFVDLFDFSAK 82
                            90       100       110       120       130       140       150       160
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 768036912    864 DLDDALRKFQSHIRVQGEAQKVERLIEAFSQRYCVCNPALVRqFRNPDTIFILAFAIILLNTDMYSPSVKaeRKMKLDDF 943
Cdd:smart00222   83 DLDQALREFLESFRLPGEAQKIDRLLEAFSSRYCECNPGVFS-KANADAAYTLAYSLIMLNTDLHNPNVK--KKMTLEDF 159
                           170       180       190
                    ....*....|....*....|....*....|
gi 768036912    944 IKNLRGVDNGEDIPRDLLVGIYQRIQGREL 973
Cdd:smart00222  160 IKNVRGSNDGEDLPREFLEELYDSIKNNEI 189
IQ_SEC7_PH pfam16453
PH domain; This PH domain is found in IQ motif and SEC7 domain-containing proteins.
995-1124 1.95e-69

PH domain; This PH domain is found in IQ motif and SEC7 domain-containing proteins.


Pssm-ID: 465120  Cd Length: 127  Bit Score: 227.93  E-value: 1.95e-69
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 768036912   995 PVLSLPHRRLVCCCQLYEVPDPNRPQRLGLHQREVFLFNDLLVVTKIFQKKKILVTYSFRQSFPLVEMHMQLFQNSYYQF 1074
Cdd:pfam16453    1 PVLALPHRRLVCYCRLFEVPDPNKKQKLGLHQREVFLFNDLLVVTKIFSKKKSSVTYSFRQSFGLLGMQVSLFENSYYPH 80
                           90       100       110       120       130
                   ....*....|....*....|....*....|....*....|....*....|
gi 768036912  1075 GIKLLSAVpggERKVLIIFNAPSLQDRLRFTSDLRESIAEVQEMEKYRVE 1124
Cdd:pfam16453   81 GIRLTSRV---DSKVLITFNARNEHDRKKFVEDLRESIAEVQEMEKLRIE 127
PH_IQSEC cd13318
IQ motif and SEC7 domain-containing protein family Pleckstrin homology domain; The IQSEC (also ...
1000-1124 1.09e-61

IQ motif and SEC7 domain-containing protein family Pleckstrin homology domain; The IQSEC (also called BRAG/Brefeldin A-resistant Arf-gunanine nucleotide exchange factor) family are a subset of Arf GEFs that have been shown to activate Arf6, which acts in the endocytic pathway to control the trafficking of a subset of cargo proteins including integrins and have key roles in the function and organization of distinct excitatory and inhibitory synapses in the retina. The family consists of 3 members: IQSEC1 (also called BRAG2/GEP100), IQSEC2 (also called BRAG1), and IQSEC3 (also called SynArfGEF, BRAG3, or KIAA1110). IQSEC1 interacts with clathrin and modulates cell adhesion by regulating integrin surface expression and in addition to Arf6, it also activates the class II Arfs, Arf4 and Arf5. Mutations in IQSEC2 cause non-syndromic X-linked intellectual disability as well as reduced activation of Arf substrates (Arf1, Arf6). IQSEC3 regulates Arf6 at inhibitory synapses and associates with the dystrophin-associated glycoprotein complex and S-SCAM. These members contains a IQ domain that may bind calmodulin, a PH domain that is thought to mediate membrane localization by binding of phosphoinositides, and a SEC7 domain that can promote GEF activity on ARF. PH domains have diverse functions, but in general are involved in targeting proteins to the appropriate cellular location or in the interaction with a binding partner. They share little sequence conservation, but all have a common fold, which is electrostatically polarized. Less than 10% of PH domains bind phosphoinositide phosphates (PIPs) with high affinity and specificity. PH domains are distinguished from other PIP-binding domains by their specific high-affinity binding to PIPs with two vicinal phosphate groups: PtdIns(3,4)P2, PtdIns(4,5)P2 or PtdIns(3,4,5)P3 which results in targeting some PH domain proteins to the plasma membrane. A few display strong specificity in lipid binding. Any specificity is usually determined by loop regions or insertions in the N-terminus of the domain, which are not conserved across all PH domains. PH domains are found in cellular signaling proteins such as serine/threonine kinase, tyrosine kinases, regulators of G-proteins, endocytotic GTPases, adaptors, as well as cytoskeletal associated molecules and in lipid associated enzymes.


Pssm-ID: 270128  Cd Length: 128  Bit Score: 206.01  E-value: 1.09e-61
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 768036912 1000 PHRRLVCCCQLYEVPDPNRPQRLGLHQREVFLFNDLLVVTKIFQKKKILVTYSFRQSFPLVEMHMQLFQNSYYQFGIKLL 1079
Cdd:cd13318     1 PHRRLVCYCRLYEVPDPNKREKPGLHQREVFLFNDLLVVTKIFSKKKSSVTYSFRQSFSLLGMQVLLFETSHYPFGIRLT 80
                          90       100       110       120
                  ....*....|....*....|....*....|....*....|....*
gi 768036912 1080 SAVPGgerKVLIIFNAPSLQDRLRFTSDLRESIAEVQEMEKYRVE 1124
Cdd:cd13318    81 SPLDN---KVLITFNARNESDRKKFVEDLRESILEVNEMESLRIE 122
PLN03076 PLN03076
ARF guanine nucleotide exchange factor (ARF-GEF); Provisional
756-978 1.73e-49

ARF guanine nucleotide exchange factor (ARF-GEF); Provisional


Pssm-ID: 215560 [Multi-domain]  Cd Length: 1780  Bit Score: 192.73  E-value: 1.73e-49
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 768036912  756 PPATGLCKQTYQRETRHSwDSPAFNNDVV---QRRHYRI----GLNLFNKKPEKGIQYLIERGFLSDTPVGVAHFILERK 828
Cdd:PLN03076  581 PVANGNGDENGEGSDSHS-ELSSETSDAAtieQRRAYKLelqeGISLFNRKPKKGIEFLINANKVGESPEEIAAFLKDAS 659
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 768036912  829 GLSRQMIGEFLGNRQkQFNRDVLDCVVDEMDFSSMDLDDALRKFQSHIRVQGEAQKVERLIEAFSQRYCVCNPalvRQFR 908
Cdd:PLN03076  660 GLNKTLIGDYLGERE-DLSLKVMHAYVDSFDFQGMEFDEAIRAFLQGFRLPGEAQKIDRIMEKFAERYCKCNP---KAFS 735
                         170       180       190       200       210       220       230
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 768036912  909 NPDTIFILAFAIILLNTDMYSPSVKAerKMKLDDFIKNLRGVDNGEDIPRDLLVGIYQRIQGRELRTNDD 978
Cdd:PLN03076  736 SADTAYVLAYSVIMLNTDAHNPMVKN--KMSADDFIRNNRGIDDGKDLPEEFMRSLYERISKNEIKMKED 803
PH_ephexin cd01221
Ephexin Pleckstrin homology (PH) domain; Ephexin-1 (also called NGEF/ neuronal guanine ...
994-1109 1.67e-04

Ephexin Pleckstrin homology (PH) domain; Ephexin-1 (also called NGEF/ neuronal guanine nucleotide exchange factor) plays a role in the homeostatic modulation of presynaptic neurotransmitter release. Specific functions are still unknown for Ephexin-2 (also called RhoGEF19) and Ephexin-3 (also called Rho guanine nucleotide exchange factor 5/RhoGEF5, Transforming immortalized mammary oncogene/p60 TIM, and NGEF/neuronalGEF). Ephexin-4 (also called RhoGEF16) acts downstream of EphA2 to promote ligand-independent breast cancer cell migration and invasion toward epidermal growth factor through activation of RhoG. This in turn results in the activation of RhoG which recruits ELMO2 and Dock4 to form a complex with EphA2 at the tips of cortactin-rich protrusions in migrating breast cancer cells. Ephexin-5 is the specific GEF for RhoA activation and the regulation of vascular smooth muscle contractility. It interacts with EPHA4 PH domains have diverse functions, but in general are involved in targeting proteins to the appropriate cellular location or in the interaction with a binding partner. The members of the Ephexin family contains a RhoGEF (DH) followed by a PH domain and an SH3 domain. The ephexin PH domain is believed to act with the DH domain in mediating protein-protein interactions. PH domains have diverse functions, but in general are involved in targeting proteins to the appropriate cellular location or in the interaction with a binding partner. They share little sequence conservation, but all have a common fold, which is electrostatically polarized. Less than 10% of PH domains bind phosphoinositide phosphates (PIPs) with high affinity and specificity. PH domains are distinguished from other PIP-binding domains by their specific high-affinity binding to PIPs with two vicinal phosphate groups: PtdIns(3,4)P2, PtdIns(4,5)P2 or PtdIns(3,4,5)P3 which results in targeting some PH domain proteins to the plasma membrane. A few display strong specificity in lipid binding. Any specificity is usually determined by loop regions or insertions in the N-terminus of the domain, which are not conserved across all PH domains. PH domains are found in cellular signaling proteins such as serine/threonine kinase, tyrosine kinases, regulators of G-proteins, endocytotic GTPases, adaptors, as well as cytoskeletal associated molecules and in lipid associated enzymes.


Pssm-ID: 269929  Cd Length: 131  Bit Score: 42.63  E-value: 1.67e-04
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 768036912  994 KPVLSlPHRRLVCCCQL--YEVPDPNRPQRLGLHQREV--FLFNDLLVVTKIFQKKKILVT-YSFRqsfPLVEM------ 1062
Cdd:cd01221     5 FPLIS-SSRWLVKRGELteLVEDGGSLTFRKKFSKTPVylFLFNDLLLITKKKSEERYLVLdYAPR---NLVQVeevedp 80
                          90       100       110       120
                  ....*....|....*....|....*....|....*....|....*..
gi 768036912 1063 HMQLFQNSYYQFGIKLLSAVPGgeRKVLIIFNAPSLQDRLRFTSDLR 1109
Cdd:cd01221    81 LQLPQPLGKNLFLLTLLENHEG--KTVELLLSAESESDRERWLSALS 125
PH smart00233
Pleckstrin homology domain; Domain commonly found in eukaryotic signalling proteins. The ...
1004-1113 1.80e-03

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


Pssm-ID: 214574 [Multi-domain]  Cd Length: 102  Bit Score: 39.07  E-value: 1.80e-03
                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 768036912   1004 LVCCCQLYEVPDPNRPQRlglHQREVFLFNDLLVvtkIFQKKKILVTYSFRQSFPLVEMHMQL---FQNSYYQFGIKLLS 1080
Cdd:smart00233    1 VIKEGWLYKKSGGGKKSW---KKRYFVLFNSTLL---YYKSKKDKKSYKPKGSIDLSGCTVREapdPDSSKKPHCFEIKT 74
                            90       100       110
                    ....*....|....*....|....*....|...
gi 768036912   1081 AvpggeRKVLIIFNAPSLQDRLRFTSDLRESIA 1113
Cdd:smart00233   75 S-----DRKTLLLQAESEEEREKWVEALRKAIA 102
PH_Phafin2-like cd01218
Phafin2 (also called EAPF, FLJ13187, ZFYVE18 or PLEKHF2) Pleckstrin Homology (PH) domain; ...
982-1062 5.37e-03

Phafin2 (also called EAPF, FLJ13187, ZFYVE18 or PLEKHF2) Pleckstrin Homology (PH) domain; Phafin2 is differentially expressed in the liver cancer cell and regulates the structure and function of the endosomes through Rab5-dependent processes. Phafin2 modulates the cell's response to extracellular stimulation by modulating the receptor density on the cell surface. Phafin2 contains a PH domain and a FYVE domain. PH domains have diverse functions, but in general are involved in targeting proteins to the appropriate cellular location or in the interaction with a binding partner. They share little sequence conservation, but all have a common fold, which is electrostatically polarized. Less than 10% of PH domains bind phosphoinositide phosphates (PIPs) with high affinity and specificity. PH domains are distinguished from other PIP-binding domains by their specific high-affinity binding to PIPs with two vicinal phosphate groups: PtdIns(3,4)P2, PtdIns(4,5)P2 or PtdIns(3,4,5)P3 which results in targeting some PH domain proteins to the plasma membrane. A few display strong specificity in lipid binding. Any specificity is usually determined by loop regions or insertions in the N-terminus of the domain, which are not conserved across all PH domains. PH domains are found in cellular signaling proteins such as serine/threonine kinase, tyrosine kinases, regulators of G-proteins, endocytotic GTPases, adaptors, as well as cytoskeletal associated molecules and in lipid associated enzymes.


Pssm-ID: 269927 [Multi-domain]  Cd Length: 123  Bit Score: 38.01  E-value: 5.37e-03
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 768036912  982 QVQAVERMIVGKKPVLSLPHRRLV--------CccqlyevpdpnrpqRLGLHQREVFLFNDLLVVTKIFQKKKilvTYSF 1053
Cdd:cd01218     8 RIAAVESCFGGSGQPLVKPGRVLVgegvltkvC--------------RKKPKPRQFFLFNDILVYGSIVINKK---KYNK 70

                  ....*....
gi 768036912 1054 RQSFPLVEM 1062
Cdd:cd01218    71 QRIIPLEDV 79
 
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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