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

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 53832028   548 QRRHYRIGLNLFNKKPEKGIQYLIERGFLSDTPVGVAHFILERKGLSRQMIGEFLGNRqKQFNRDVLDCVVDEMDFSSMD 627
Cdd:pfam01369   1 RKKLLREGIEKFNKKPKKGIEYLIEKGFIEDDPESIAKFLFETPGLDKKAIGEYLGKP-DEFNIEVLKAFVDLFDFKGLR 79

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 53832028   628 LDDALRKFQSHIRVQGEAQKVERLIEAFSQRYCVCNPalvRQFRNPDTIFILAFAIILLNTDMYSPSVKaeRKMKLDDFI 707
Cdd:pfam01369  80 IDEALRLFLESFRLPGEAQKIDRIMEAFAERYYEQNP---GVFANADAAYVLAYSIIMLNTDLHNPNVK--KKMTLEDFI 154

                         170       180
                  ....*....|....*....|....*....
gi 53832028   708 KNLRGVDNGEDIPRDLLVGIYQRIQGREL 736
Cdd:pfam01369 155 RNLRGINDGKDFPDEYLEEIYDSIKKNEI 183

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

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 53832028   548 QRRHYRIGLNLFNKKPEKGIQYLIERGFLSDTPVGVAHFILERKGLSRQMIGEFLGNRqKQFNRDVLDCVVDEMDFSSMD 627
Cdd:pfam01369   1 RKKLLREGIEKFNKKPKKGIEYLIEKGFIEDDPESIAKFLFETPGLDKKAIGEYLGKP-DEFNIEVLKAFVDLFDFKGLR 79

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 53832028   628 LDDALRKFQSHIRVQGEAQKVERLIEAFSQRYCVCNPalvRQFRNPDTIFILAFAIILLNTDMYSPSVKaeRKMKLDDFI 707
Cdd:pfam01369  80 IDEALRLFLESFRLPGEAQKIDRIMEAFAERYYEQNP---GVFANADAAYVLAYSIIMLNTDLHNPNVK--KKMTLEDFI 154

                         170       180
                  ....*....|....*....|....*....
gi 53832028   708 KNLRGVDNGEDIPRDLLVGIYQRIQGREL 736
Cdd:pfam01369 155 RNLRGINDGKDFPDEYLEEIYDSIKKNEI 183

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).

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 53832028    548 QRRHYRIGLNLFNKKPEKGIQYLIERGFL-SDTPVGVAHFILERKGLSRQMIGEFLGNRqKQFNRDVLDCVVDEMDFSSM 626
Cdd:smart00222   4 RKKLLSEGIVKFNDKPKKGIQSLQEKGFLaNEDPQDVADFLSKNEGLNKKAIGDYLGEH-DEFNRLVLHAFVDLFDFSAK 82

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 53832028    627 DLDDALRKFQSHIRVQGEAQKVERLIEAFSQRYCVCNPALVRqFRNPDTIFILAFAIILLNTDMYSPSVKaeRKMKLDDF 706
Cdd:smart00222  83 DLDQALREFLESFRLPGEAQKIDRLLEAFSSRYCECNPGVFS-KANADAAYTLAYSLIMLNTDLHNPNVK--KKMTLEDF 159

                          170       180       190
                   ....*....|....*....|....*....|
gi 53832028    707 IKNLRGVDNGEDIPRDLLVGIYQRIQGREL 736
Cdd:smart00222 160 IKNVRGSNDGEDLPREFLEELYDSIKNNEI 189

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.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 53832028 763 PHRRLVCCCQLYEVPDPNRPQRLGLHQREVFLFNDLLVVTKIFQKKKILVTYSFRQSFPLVEMHMQLFQNSYYQFGIKLL 842
Cdd:cd13318   1 PHRRLVCYCRLYEVPDPNKREKPGLHQREVFLFNDLLVVTKIFSKKKSSVTYSFRQSFSLLGMQVLLFETSHYPFGIRLT 80

                        90       100       110       120       130
                ....*....|....*....|....*....|....*....|....*....|.
gi 53832028 843 SAVPGgerKVLIIFNAPSLQDRLRFTSDLRESIAEVQEMEKYRVESELEKQ 893
Cdd:cd13318  81 SPLDN---KVLITFNARNESDRKKFVEDLRESILEVNEMESLRIEEELEKQ 128

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.

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 53832028    767 LVCCCQLYEVPDPNRPQRlglHQREVFLFNDLLVvtkIFQKKKILVTYSFRQSFPLVEMHMQL---FQNSYYQFGIKLLS 843
Cdd:smart00233   1 VIKEGWLYKKSGGGKKSW---KKRYFVLFNSTLL---YYKSKKDKKSYKPKGSIDLSGCTVREapdPDSSKKPHCFEIKT 74

                           90       100       110
                   ....*....|....*....|....*....|...
gi 53832028    844 AvpggeRKVLIIFNAPSLQDRLRFTSDLRESIA 876
Cdd:smart00233  75 S-----DRKTLLLQAESEEEREKWVEALRKAIA 102

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

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 53832028   548 QRRHYRIGLNLFNKKPEKGIQYLIERGFLSDTPVGVAHFILERKGLSRQMIGEFLGNRqKQFNRDVLDCVVDEMDFSSMD 627
Cdd:pfam01369   1 RKKLLREGIEKFNKKPKKGIEYLIEKGFIEDDPESIAKFLFETPGLDKKAIGEYLGKP-DEFNIEVLKAFVDLFDFKGLR 79

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 53832028   628 LDDALRKFQSHIRVQGEAQKVERLIEAFSQRYCVCNPalvRQFRNPDTIFILAFAIILLNTDMYSPSVKaeRKMKLDDFI 707
Cdd:pfam01369  80 IDEALRLFLESFRLPGEAQKIDRIMEAFAERYYEQNP---GVFANADAAYVLAYSIIMLNTDLHNPNVK--KKMTLEDFI 154

                         170       180
                  ....*....|....*....|....*....
gi 53832028   708 KNLRGVDNGEDIPRDLLVGIYQRIQGREL 736
Cdd:pfam01369 155 RNLRGINDGKDFPDEYLEEIYDSIKKNEI 183

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).

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 53832028    548 QRRHYRIGLNLFNKKPEKGIQYLIERGFL-SDTPVGVAHFILERKGLSRQMIGEFLGNRqKQFNRDVLDCVVDEMDFSSM 626
Cdd:smart00222   4 RKKLLSEGIVKFNDKPKKGIQSLQEKGFLaNEDPQDVADFLSKNEGLNKKAIGDYLGEH-DEFNRLVLHAFVDLFDFSAK 82

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 53832028    627 DLDDALRKFQSHIRVQGEAQKVERLIEAFSQRYCVCNPALVRqFRNPDTIFILAFAIILLNTDMYSPSVKaeRKMKLDDF 706
Cdd:smart00222  83 DLDQALREFLESFRLPGEAQKIDRLLEAFSSRYCECNPGVFS-KANADAAYTLAYSLIMLNTDLHNPNVK--KKMTLEDF 159

                          170       180       190
                   ....*....|....*....|....*....|
gi 53832028    707 IKNLRGVDNGEDIPRDLLVGIYQRIQGREL 736
Cdd:smart00222 160 IKNVRGSNDGEDLPREFLEELYDSIKNNEI 189

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.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 53832028 763 PHRRLVCCCQLYEVPDPNRPQRLGLHQREVFLFNDLLVVTKIFQKKKILVTYSFRQSFPLVEMHMQLFQNSYYQFGIKLL 842
Cdd:cd13318   1 PHRRLVCYCRLYEVPDPNKREKPGLHQREVFLFNDLLVVTKIFSKKKSSVTYSFRQSFSLLGMQVLLFETSHYPFGIRLT 80

                        90       100       110       120       130
                ....*....|....*....|....*....|....*....|....*....|.
gi 53832028 843 SAVPGgerKVLIIFNAPSLQDRLRFTSDLRESIAEVQEMEKYRVESELEKQ 893
Cdd:cd13318  81 SPLDN---KVLITFNARNESDRKKFVEDLRESILEVNEMESLRIEEELEKQ 128

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.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 53832028 757 KPVLSlPHRRLVCCCQL--YEVPDPNRPQRLGLHQREV--FLFNDLLVVTKIFQKKKILVT-YSFRqsfPLVEM------ 825
Cdd:cd01221   5 FPLIS-SSRWLVKRGELteLVEDGGSLTFRKKFSKTPVylFLFNDLLLITKKKSEERYLVLdYAPR---NLVQVeevedp 80

                        90       100       110       120
                ....*....|....*....|....*....|....*....|....*..
gi 53832028 826 HMQLFQNSYYQFGIKLLSAVPGgeRKVLIIFNAPSLQDRLRFTSDLR 872
Cdd:cd01221  81 LQLPQPLGKNLFLLTLLENHEG--KTVELLLSAESESDRERWLSALS 125

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.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 53832028 745 QVQAVERMIVGKKPVLSLPHRRLV--------CccqlyevpdpnrpqRLGLHQREVFLFNDLLVVTKIFQKKKilvTYSF 816
Cdd:cd01218   8 RIAAVESCFGGSGQPLVKPGRVLVgegvltkvC--------------RKKPKPRQFFLFNDILVYGSIVINKK---KYNK 70

                ....*....
gi 53832028 817 RQSFPLVEM 825
Cdd:cd01218  71 QRIIPLEDV 79