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

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767924788   622 CVLSLPHRRLVCYCRLFEVPDPNKPQKLGLHQREIFLFNDLLVVTKIFQKKKNSVTYSFRQSFSLYGMQVLLFENQYYPN 701
Cdd:pfam16453    1 PVLALPHRRLVCYCRLFEVPDPNKKQKLGLHQREVFLFNDLLVVTKIFSKKKSSVTYSFRQSFGLLGMQVSLFENSYYPH 80

                           90       100       110       120       130
                   ....*....|....*....|....*....|....*....|....*....|
gi 767924788   702 GIRLTSSVpgaDIKVLINFNAPNPQDRKKFTDDLRESIAEVQEMEKHRIE 751
Cdd:pfam16453   81 GIRLTSRV---DSKVLITFNARNEHDRKKFVEDLRESIAEVQEMEKLRIE 127

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.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767924788  402 RKRHYRIGLNLFNKKPEKGVQYLIERGFV-PDTPVGVAHFLLQRKGLSRQMIGEFLGNRQkQFNRDVLDCVVDEMDFSTM 480
Cdd:cd00171     1 RKTLLSEGRQLFNRKPKKGISFLIEKGFLeDDSPKEIAKFLYETEGLNKKAIGEYLGENN-EFNSLVLHEFVDLFDFSGL 79

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767924788  481 ELDEALRKFQAHIRVQGEAQKVERLIEAFSQRYCICNPGVVrqFRNPDTIFILAFAIILLNTDMYSPNVKpeRKMKLEDF 560
Cdd:cd00171    80 RLDEALRKFLQSFRLPGEAQKIDRLLEKFSERYCECNPGIF--SSSADAAYTLAYSIIMLNTDLHNPNVK--KKMTLEDF 155

                         170       180       190
                  ....*....|....*....|....*....|
gi 767924788  561 IKNLRGVDDGEDIPREMLMGIYERIRKREL 590
Cdd:cd00171   156 IKNLRGINDGEDFPREFLKELYDSIKNNEI 185

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 767924788  627 PHRRLVCYCRLFEVPDPNKPQKLGLHQREIFLFNDLLVVTKIFQKKKNSVTYSFRQSFSLYGMQVLLFENQYYPNGIRLT 706
Cdd:cd13318     1 PHRRLVCYCRLYEVPDPNKREKPGLHQREVFLFNDLLVVTKIFSKKKSSVTYSFRQSFSLLGMQVLLFETSHYPFGIRLT 80

                          90       100       110       120       130
                  ....*....|....*....|....*....|....*....|....*....|.
gi 767924788  707 SSVpgaDIKVLINFNAPNPQDRKKFTDDLRESIAEVQEMEKHRIESELEKQ 757
Cdd:cd13318    81 SPL---DNKVLITFNARNESDRKKFVEDLRESILEVNEMESLRIEEELEKQ 128

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

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767924788  402 RKRHYRI----GLNLFNKKPEKGVQYLIERGFVPDTPVGVAHFLLQRKGLSRQMIGEFLGNRQkQFNRDVLDCVVDEMDF 477
Cdd:PLN03076  612 QRRAYKLelqeGISLFNRKPKKGIEFLINANKVGESPEEIAAFLKDASGLNKTLIGDYLGERE-DLSLKVMHAYVDSFDF 690

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767924788  478 STMELDEALRKFQAHIRVQGEAQKVERLIEAFSQRYCICNPGVvrqFRNPDTIFILAFAIILLNTDMYSPNVKpeRKMKL 557
Cdd:PLN03076  691 QGMEFDEAIRAFLQGFRLPGEAQKIDRIMEKFAERYCKCNPKA---FSSADTAYVLAYSVIMLNTDAHNPMVK--NKMSA 765

                         170       180       190       200
                  ....*....|....*....|....*....|....*....|....*
gi 767924788  558 EDFIKNLRGVDDGEDIPREMLMGIYERIRKRELKTNEDHVSQVQK 602
Cdd:PLN03076  766 DDFIRNNRGIDDGKDLPEEFMRSLYERISKNEIKMKEDDLVPQQK 810

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.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767924788  402 RKRHYRIGLNLFNKKPEKGVQYLIERGFV-PDTPVGVAHFLLQRKGLSRQMIGEFLGNRQkQFNRDVLDCVVDEMDFSTM 480
Cdd:cd00171     1 RKTLLSEGRQLFNRKPKKGISFLIEKGFLeDDSPKEIAKFLYETEGLNKKAIGEYLGENN-EFNSLVLHEFVDLFDFSGL 79

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767924788  481 ELDEALRKFQAHIRVQGEAQKVERLIEAFSQRYCICNPGVVrqFRNPDTIFILAFAIILLNTDMYSPNVKpeRKMKLEDF 560
Cdd:cd00171    80 RLDEALRKFLQSFRLPGEAQKIDRLLEKFSERYCECNPGIF--SSSADAAYTLAYSIIMLNTDLHNPNVK--KKMTLEDF 155

                         170       180       190
                  ....*....|....*....|....*....|
gi 767924788  561 IKNLRGVDDGEDIPREMLMGIYERIRKREL 590
Cdd:cd00171   156 IKNLRGINDGEDFPREFLKELYDSIKNNEI 185

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 767924788  627 PHRRLVCYCRLFEVPDPNKPQKLGLHQREIFLFNDLLVVTKIFQKKKNSVTYSFRQSFSLYGMQVLLFENQYYPNGIRLT 706
Cdd:cd13318     1 PHRRLVCYCRLYEVPDPNKREKPGLHQREVFLFNDLLVVTKIFSKKKSSVTYSFRQSFSLLGMQVLLFETSHYPFGIRLT 80

                          90       100       110       120       130
                  ....*....|....*....|....*....|....*....|....*....|.
gi 767924788  707 SSVpgaDIKVLINFNAPNPQDRKKFTDDLRESIAEVQEMEKHRIESELEKQ 757
Cdd:cd13318    81 SPL---DNKVLITFNARNESDRKKFVEDLRESILEVNEMESLRIEEELEKQ 128

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

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767924788  402 RKRHYRI----GLNLFNKKPEKGVQYLIERGFVPDTPVGVAHFLLQRKGLSRQMIGEFLGNRQkQFNRDVLDCVVDEMDF 477
Cdd:PLN03076  612 QRRAYKLelqeGISLFNRKPKKGIEFLINANKVGESPEEIAAFLKDASGLNKTLIGDYLGERE-DLSLKVMHAYVDSFDF 690

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767924788  478 STMELDEALRKFQAHIRVQGEAQKVERLIEAFSQRYCICNPGVvrqFRNPDTIFILAFAIILLNTDMYSPNVKpeRKMKL 557
Cdd:PLN03076  691 QGMEFDEAIRAFLQGFRLPGEAQKIDRIMEKFAERYCKCNPKA---FSSADTAYVLAYSVIMLNTDAHNPMVK--NKMSA 765

                         170       180       190       200
                  ....*....|....*....|....*....|....*....|....*
gi 767924788  558 EDFIKNLRGVDDGEDIPREMLMGIYERIRKRELKTNEDHVSQVQK 602
Cdd:PLN03076  766 DDFIRNNRGIDDGKDLPEEFMRSLYERISKNEIKMKEDDLVPQQK 810

FYVE, RhoGEF and PH domain containing/faciogenital dysplasia proteins 5 and 6, N-terminal Pleckstrin Homology (PH) domain; FGD5 regulates promotes angiogenesis of vascular endothelial growth factor (VEGF) in vascular endothelial cells, including network formation, permeability, directional movement, and proliferation. The specific function of FGD6 is unknown. In general, FGDs have a RhoGEF (DH) domain, followed by a PH domain, a FYVE domain and a C-terminal PH domain. All FGDs are guanine nucleotide exchange factors that activate the Rho GTPase Cdc42, an important regulator of membrane trafficking. The RhoGEF domain is responsible for GEF catalytic activity, while the PH domain is involved in intracellular targeting of the DH 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 767924788  651 LHQREIFLFNDLLVVTKIFQkkkNSVTYSFRQSFSLYGMQVLLFENQYYPNGIRLTSSVPGADIKvlinfnAPNPQDRKK 730
Cdd:cd13389    28 MQPRYFFLFNDCLLYTTPVQ---SSGMLKLNNELPLSGMKVKLPEDEEYSNEFQIISTKRSFTLI------ASSEEERDE 98

                          90
                  ....*....|.
gi 767924788  731 FTDDLRESIAE 741
Cdd:cd13389    99 WVKALSRAIEE 109