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 767971320   651 RKRLYRIGLNLFNINPDKGIQFLISRGFIPDTPIGVAHFLLQRKGLSRQMIGEFLGNsKKQFNRDVLDCVVDEMDFSSME 730
Cdd:pfam01369    1 RKKLLREGIEKFNKKPKKGIEYLIEKGFIEDDPESIAKFLFETPGLDKKAIGEYLGK-PDEFNIEVLKAFVDLFDFKGLR 79

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767971320   731 LDEALRKFQAHIRVQGEAQKVERLIEAFSQRYCMCNPEVvqqFHNPDTIFILAFAIILLNTDMYSPNIKpdRKMMLEDFI 810
Cdd:pfam01369   80 IDEALRLFLESFRLPGEAQKIDRIMEAFAERYYEQNPGV---FANADAAYVLAYSIIMLNTDLHNPNVK--KKMTLEDFI 154

                          170       180
                   ....*....|....*....|....*....
gi 767971320   811 RNLRGVDDGADIPRELVVGIYERIQQKEL 839
Cdd:pfam01369  155 RNLRGINDGKDFPDEYLEEIYDSIKKNEI 183

Prolipoprotein diacylglyceryl transferase;

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767971320  444 AGPPGLEAEGR-------APESAGPGPG-----DDAAETPGLPPAHSGTLMMAFR---DVTVQIANQNISVSSSTALSVA 508
Cdd:PRK13108  274 LAPKGREAPGAlrgseyvVDEALEREPAelaaaAVASAASAVGPVGPGEPNQPDDvaeAVKAEVAEVTDEVAAESVVQVA 353

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|....*..
gi 767971320  509 NCLGAQT--VQAPAEPAAGKAEQGETSGrEAPEAPAVGREDASAEDS 553
Cdd:PRK13108  354 DRDGESTpaVEETSEADIEREQPGDLAG-QAPAAHQVDAEAASAAPE 399

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 767971320   651 RKRLYRIGLNLFNINPDKGIQFLISRGFIPDTPIGVAHFLLQRKGLSRQMIGEFLGNsKKQFNRDVLDCVVDEMDFSSME 730
Cdd:pfam01369    1 RKKLLREGIEKFNKKPKKGIEYLIEKGFIEDDPESIAKFLFETPGLDKKAIGEYLGK-PDEFNIEVLKAFVDLFDFKGLR 79

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767971320   731 LDEALRKFQAHIRVQGEAQKVERLIEAFSQRYCMCNPEVvqqFHNPDTIFILAFAIILLNTDMYSPNIKpdRKMMLEDFI 810
Cdd:pfam01369   80 IDEALRLFLESFRLPGEAQKIDRIMEAFAERYYEQNPGV---FANADAAYVLAYSIIMLNTDLHNPNVK--KKMTLEDFI 154

                          170       180
                   ....*....|....*....|....*....
gi 767971320   811 RNLRGVDDGADIPRELVVGIYERIQQKEL 839
Cdd:pfam01369  155 RNLRGINDGKDFPDEYLEEIYDSIKKNEI 183

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

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767971320   861 TVLSVPHRRLVCCSRLFEVTDVNKLQKQAAHQREVFLFNDLLVILKLCPKKKSSSTYTFCKSVGLLGMQFQLFENEYYSH 940
Cdd:pfam16453    1 PVLALPHRRLVCYCRLFEVPDPNKKQKLGLHQREVFLFNDLLVVTKIFSKKKSSVTYSFRQSFGLLGMQVSLFENSYYPH 80

                           90       100       110       120       130
                   ....*....|....*....|....*....|....*....|....*....|
gi 767971320   941 GITLVTPLsgsEKKQVLHFCALGSDEMQKFVEDLKESIAEVTELEQIRIE 990
Cdd:pfam16453   81 GIRLTSRV---DSKVLITFNARNEHDRKKFVEDLRESIAEVQEMEKLRIE 127

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 767971320  866 PHRRLVCCSRLFEVTDVNKLQKQAAHQREVFLFNDLLVILKLCPKKKSSSTYTFCKSVGLLGMQFQLFENEYYSHGITLV 945
Cdd:cd13318     1 PHRRLVCYCRLYEVPDPNKREKPGLHQREVFLFNDLLVVTKIFSKKKSSVTYSFRQSFSLLGMQVLLFETSHYPFGIRLT 80

                          90       100       110       120       130
                  ....*....|....*....|....*....|....*....|....*....|.
gi 767971320  946 TPLSGsekKQVLHFCALGSDEMQKFVEDLKESIAEVTELEQIRIEWELEKQ 996
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 767971320    891 HQREVFLFNDLLVilkLCPKKKSSSTYTFCKSVGLLGMQFQLFENEY---YSHGITLVTPlsgseKKQVLHFCALGSDEM 967
Cdd:smart00233   19 KKRYFVLFNSTLL---YYKSKKDKKSYKPKGSIDLSGCTVREAPDPDsskKPHCFEIKTS-----DRKTLLLQAESEEER 90

                            90
                    ....*....|..
gi 767971320    968 QKFVEDLKESIA 979
Cdd:smart00233   91 EKWVEALRKAIA 102

Basic leucine zipper (bZIP) domain of bZIP transcription factors: a DNA-binding and dimerization domain; Basic leucine zipper (bZIP) factors comprise one of the most important classes of enhancer-type transcription factors. They act in networks of homo and heterodimers in the regulation of a diverse set of cellular processes including cell survival, learning and memory, lipid metabolism, and cancer progression, among others. They also play important roles in responses to stimuli or stress signals such as cytokines, genotoxic agents, or physiological stresses. The bZIP structural motif contains a basic region and a leucine zipper, composed of alpha helices with leucine residues 7 amino acids apart, which stabilize dimerization with a parallel leucine zipper domain. Dimerization of leucine zippers creates a pair of the adjacent basic regions that bind DNA and undergo conformational change. Dimerization occurs in a specific and predictable manner resulting in hundreds of dimers having unique effects on transcription.

                          10        20        30
                  ....*....|....*....|....*....|..
gi 767971320   32 QRERIDELERRLDELSAENRSLWEHQQLLQAQ 63
Cdd:cd14686    19 KKERIEELEEEVEELEEENEELKAELEELRAE 50

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 767971320   651 RKRLYRIGLNLFNINPDKGIQFLISRGFIPDTPIGVAHFLLQRKGLSRQMIGEFLGNsKKQFNRDVLDCVVDEMDFSSME 730
Cdd:pfam01369    1 RKKLLREGIEKFNKKPKKGIEYLIEKGFIEDDPESIAKFLFETPGLDKKAIGEYLGK-PDEFNIEVLKAFVDLFDFKGLR 79

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767971320   731 LDEALRKFQAHIRVQGEAQKVERLIEAFSQRYCMCNPEVvqqFHNPDTIFILAFAIILLNTDMYSPNIKpdRKMMLEDFI 810
Cdd:pfam01369   80 IDEALRLFLESFRLPGEAQKIDRIMEAFAERYYEQNPGV---FANADAAYVLAYSIIMLNTDLHNPNVK--KKMTLEDFI 154

                          170       180
                   ....*....|....*....|....*....
gi 767971320   811 RNLRGVDDGADIPRELVVGIYERIQQKEL 839
Cdd:pfam01369  155 RNLRGINDGKDFPDEYLEEIYDSIKKNEI 183

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

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767971320   861 TVLSVPHRRLVCCSRLFEVTDVNKLQKQAAHQREVFLFNDLLVILKLCPKKKSSSTYTFCKSVGLLGMQFQLFENEYYSH 940
Cdd:pfam16453    1 PVLALPHRRLVCYCRLFEVPDPNKKQKLGLHQREVFLFNDLLVVTKIFSKKKSSVTYSFRQSFGLLGMQVSLFENSYYPH 80

                           90       100       110       120       130
                   ....*....|....*....|....*....|....*....|....*....|
gi 767971320   941 GITLVTPLsgsEKKQVLHFCALGSDEMQKFVEDLKESIAEVTELEQIRIE 990
Cdd:pfam16453   81 GIRLTSRV---DSKVLITFNARNEHDRKKFVEDLRESIAEVQEMEKLRIE 127

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 767971320  866 PHRRLVCCSRLFEVTDVNKLQKQAAHQREVFLFNDLLVILKLCPKKKSSSTYTFCKSVGLLGMQFQLFENEYYSHGITLV 945
Cdd:cd13318     1 PHRRLVCYCRLYEVPDPNKREKPGLHQREVFLFNDLLVVTKIFSKKKSSVTYSFRQSFSLLGMQVLLFETSHYPFGIRLT 80

                          90       100       110       120       130
                  ....*....|....*....|....*....|....*....|....*....|.
gi 767971320  946 TPLSGsekKQVLHFCALGSDEMQKFVEDLKESIAEVTELEQIRIEWELEKQ 996
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 767971320    891 HQREVFLFNDLLVilkLCPKKKSSSTYTFCKSVGLLGMQFQLFENEY---YSHGITLVTPlsgseKKQVLHFCALGSDEM 967
Cdd:smart00233   19 KKRYFVLFNSTLL---YYKSKKDKKSYKPKGSIDLSGCTVREAPDPDsskKPHCFEIKTS-----DRKTLLLQAESEEER 90

                            90
                    ....*....|..
gi 767971320    968 QKFVEDLKESIA 979
Cdd:smart00233   91 EKWVEALRKAIA 102

Pleckstrin homology (PH) 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 767971320  891 HQREVFLFNDLLVILKlcpkKKSSSTYTFCKSVGLLG-MQFQLFENEYYSHGITLVTPlsgseKKQVLHFCALGSDEMQK 969
Cdd:cd00821    17 KKRWFVLFEGVLLYYK----SKKDSSYKPKGSIPLSGiLEVEEVSPKERPHCFELVTP-----DGRTYYLQADSEEERQE 87

                  ....*
gi 767971320  970 FVEDL 974
Cdd:cd00821    88 WLKAL 92

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 767971320  884 KLQKQAAHQREVFLFNDLLVIlklCPKKKSSSTYTFCKSVGLLGMQFQLFENEYYSHGITLVtplsgSEKKQVLhFCALG 963
Cdd:cd13389    22 KVSRKEMQPRYFFLFNDCLLY---TTPVQSSGMLKLNNELPLSGMKVKLPEDEEYSNEFQII-----STKRSFT-LIASS 92

                          90
                  ....*....|....*..
gi 767971320  964 SDEMQKFVEDLKESIAE 980
Cdd:cd13389    93 EEERDEWVKALSRAIEE 109