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 578838189   785 QRRHYRIGLNLFNKKPEKGIQYLIERGFLSDTPVGVAHFILERKGLSRQMIGEFLGNRqKQFNRDVLDCVVDEMDFSSMD 864
Cdd:pfam01369    1 RKKLLREGIEKFNKKPKKGIEYLIEKGFIEDDPESIAKFLFETPGLDKKAIGEYLGKP-DEFNIEVLKAFVDLFDFKGLR 79

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 578838189   865 LDDALRKFQSHIRVQGEAQKVERLIEAFSQRYCVCNPalvRQFRNPDTIFILAFAIILLNTDMYSPSVKaeRKMKLDDFI 944
Cdd:pfam01369   80 IDEALRLFLESFRLPGEAQKIDRIMEAFAERYYEQNP---GVFANADAAYVLAYSIIMLNTDLHNPNVK--KKMTLEDFI 154

                          170       180
                   ....*....|....*....|....*....
gi 578838189   945 KNLRGVDNGEDIPRDLLVGIYQRIQGREL 973
Cdd:pfam01369  155 RNLRGINDGKDFPDEYLEEIYDSIKKNEI 183

N-terminal domain of Kruppel-like factor (KLF) 1, KLF2, KLF4, and similar proteins; Kruppel/Krueppel-like transcription factors (KLFs) belong to a family of proteins called the Specificity Protein (SP)/KLF family, characterized by a C-terminal DNA-binding domain of 81 amino acids consisting of three Kruppel-like C2H2 zinc fingers. These factors bind to a loose consensus motif, namely NNRCRCCYY (where N is any nucleotide; R is A/G, and Y is C/T), such as the recurring motifs in GC and GT boxes (5'-GGGGCGGGG-3' and 5-GGTGTGGGG-3') that are present in promoters and more distal regulatory elements of mammalian genes. Members of the KLF family can act as activators or repressors of transcription depending on cell and promoter context. KLFs regulate various cellular functions, such as proliferation, differentiation, and apoptosis, as well as the development and homeostasis of several types of tissue. In addition to the C-terminal DNA-binding domain, each KLF also has a unique N-terminal activation/repression domain that confers specifity and allows it to bind specifically to a certain partner, leading to distinct activities in vivo. This model represents the related N-terminal domains of KLF1, KLF2, KLF4, and similar proteins.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 578838189 1350 PHRHFHAHGPVPGPQHYTLGRPGRAPRRGAGGHPQFAPHGRHPLHQPTSPLPLYSPAPQHPPAHKQGPKHF--IFSHHPQ 1427
Cdd:cd22056   209 PKHQMHSVHPQAFTHHQAAGPGALQGRGGRGGPDCHLLHSSHHHHHHHHLQYQYMNAPYPPHYAHQGAPQFhgQYSVFRE 288

                          90       100       110
                  ....*....|....*....|....*....|
gi 578838189 1428 MMPAAgaaggpgsrppggsysHPHHPQSPL 1457
Cdd:cd22056   289 PMRVH----------------HQGHPGSML 302

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 578838189   785 QRRHYRIGLNLFNKKPEKGIQYLIERGFLSDTPVGVAHFILERKGLSRQMIGEFLGNRqKQFNRDVLDCVVDEMDFSSMD 864
Cdd:pfam01369    1 RKKLLREGIEKFNKKPKKGIEYLIEKGFIEDDPESIAKFLFETPGLDKKAIGEYLGKP-DEFNIEVLKAFVDLFDFKGLR 79

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 578838189   865 LDDALRKFQSHIRVQGEAQKVERLIEAFSQRYCVCNPalvRQFRNPDTIFILAFAIILLNTDMYSPSVKaeRKMKLDDFI 944
Cdd:pfam01369   80 IDEALRLFLESFRLPGEAQKIDRIMEAFAERYYEQNP---GVFANADAAYVLAYSIIMLNTDLHNPNVK--KKMTLEDFI 154

                          170       180
                   ....*....|....*....|....*....
gi 578838189   945 KNLRGVDNGEDIPRDLLVGIYQRIQGREL 973
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 578838189    785 QRRHYRIGLNLFNKKPEKGIQYLIERGFL-SDTPVGVAHFILERKGLSRQMIGEFLGNRqKQFNRDVLDCVVDEMDFSSM 863
Cdd:smart00222    4 RKKLLSEGIVKFNDKPKKGIQSLQEKGFLaNEDPQDVADFLSKNEGLNKKAIGDYLGEH-DEFNRLVLHAFVDLFDFSAK 82

                            90       100       110       120       130       140       150       160
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 578838189    864 DLDDALRKFQSHIRVQGEAQKVERLIEAFSQRYCVCNPALVRqFRNPDTIFILAFAIILLNTDMYSPSVKaeRKMKLDDF 943
Cdd:smart00222   83 DLDQALREFLESFRLPGEAQKIDRLLEAFSSRYCECNPGVFS-KANADAAYTLAYSLIMLNTDLHNPNVK--KKMTLEDF 159

                           170       180       190
                    ....*....|....*....|....*....|
gi 578838189    944 IKNLRGVDNGEDIPRDLLVGIYQRIQGREL 973
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 578838189 1000 PHRRLVCCCQLYEVPDPNRPQRLGLHQREVFLFNDLLVVTKIFQKKKILVTYSFRQSFPLVEMHMQLFQNSYYQFGIKLL 1079
Cdd:cd13318     1 PHRRLVCYCRLYEVPDPNKREKPGLHQREVFLFNDLLVVTKIFSKKKSSVTYSFRQSFSLLGMQVLLFETSHYPFGIRLT 80

                          90       100       110       120       130
                  ....*....|....*....|....*....|....*....|....*....|.
gi 578838189 1080 SAVPGgerKVLIIFNAPSLQDRLRFTSDLRESIAEVQEMEKYRVESELEKQ 1130
Cdd:cd13318    81 SPLDN---KVLITFNARNESDRKKFVEDLRESILEVNEMESLRIEEELEKQ 128

N-terminal domain of Kruppel-like factors with similarity to the N-terminal domains of Kruppel-like factor (KLF)1, KLF2, and KLF4; Kruppel/Krueppel-like transcription factors (KLFs) belong to a family of proteins called the Specificity Protein (SP)/KLF family, characterized by a C-terminal DNA-binding domain of 81 amino acids consisting of three Kruppel-like C2H2 zinc fingers. These factors bind to a loose consensus motif, namely NNRCRCCYY (where N is any nucleotide; R is A/G, and Y is C/T), such as the recurring motifs in GC and GT boxes (5'-GGGGCGGGG-3' and 5-GGTGTGGGG-3') that are present in promoters and more distal regulatory elements of mammalian genes. Members of the KLF family can act as activators or repressors of transcription depending on cell and promoter context. KLFs regulate various cellular functions, such as proliferation, differentiation, and apoptosis, as well as the development and homeostasis of several types of tissue. In addition to the C-terminal DNA-binding domain, each KLF also has a unique N-terminal activation/repression domain that confers specifity and allows it to bind specifically to a certain partner, leading to distinct activities in vivo. This model represents the N-terminal domains of an unknown subfamily of KLFs, predominantly found in fish, related to the N-terminal domains of KLF1, KLF2, and KLF4.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 578838189 1350 PHRHFHAHGPVPGPQHYTLGRPGRAPRRGAGGHPQFAPHGRHPLHQPTSPLPLYSPAPQHPPAHKQGPKHF--IFSHHPQ 1427
Cdd:cd22056   209 PKHQMHSVHPQAFTHHQAAGPGALQGRGGRGGPDCHLLHSSHHHHHHHHLQYQYMNAPYPPHYAHQGAPQFhgQYSVFRE 288

                          90       100       110
                  ....*....|....*....|....*....|
gi 578838189 1428 MMPAAgaaggpgsrppggsysHPHHPQSPL 1457
Cdd:cd22056   289 PMRVH----------------HQGHPGSML 302

Autophagy protein 16 (ATG16); Autophagy is a ubiquitous intracellular degradation system for eukaryotic cells. During autophagy, cytoplasmic components are enclosed in autophagosomes and delivered to lysosomes/vacuoles. ATG16 (also known as Apg16) has been shown to be bind to Apg5 and is required for the function of the Apg12p-Apg5p conjugate in the yeast autophagy pathway.

                           10        20        30        40
                   ....*....|....*....|....*....|....*....|..
gi 578838189    23 LLELNNIIESQQQLLETQRRRIEELEGQLDQLTQENRDLREE 64
Cdd:pfam08614   80 LVDLNEELQELEKKLREDERRLAALEAERAQLEEKLKDREEE 121

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 578838189   785 QRRHYRIGLNLFNKKPEKGIQYLIERGFLSDTPVGVAHFILERKGLSRQMIGEFLGNRqKQFNRDVLDCVVDEMDFSSMD 864
Cdd:pfam01369    1 RKKLLREGIEKFNKKPKKGIEYLIEKGFIEDDPESIAKFLFETPGLDKKAIGEYLGKP-DEFNIEVLKAFVDLFDFKGLR 79

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 578838189   865 LDDALRKFQSHIRVQGEAQKVERLIEAFSQRYCVCNPalvRQFRNPDTIFILAFAIILLNTDMYSPSVKaeRKMKLDDFI 944
Cdd:pfam01369   80 IDEALRLFLESFRLPGEAQKIDRIMEAFAERYYEQNP---GVFANADAAYVLAYSIIMLNTDLHNPNVK--KKMTLEDFI 154

                          170       180
                   ....*....|....*....|....*....
gi 578838189   945 KNLRGVDNGEDIPRDLLVGIYQRIQGREL 973
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 578838189    785 QRRHYRIGLNLFNKKPEKGIQYLIERGFL-SDTPVGVAHFILERKGLSRQMIGEFLGNRqKQFNRDVLDCVVDEMDFSSM 863
Cdd:smart00222    4 RKKLLSEGIVKFNDKPKKGIQSLQEKGFLaNEDPQDVADFLSKNEGLNKKAIGDYLGEH-DEFNRLVLHAFVDLFDFSAK 82

                            90       100       110       120       130       140       150       160
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 578838189    864 DLDDALRKFQSHIRVQGEAQKVERLIEAFSQRYCVCNPALVRqFRNPDTIFILAFAIILLNTDMYSPSVKaeRKMKLDDF 943
Cdd:smart00222   83 DLDQALREFLESFRLPGEAQKIDRLLEAFSSRYCECNPGVFS-KANADAAYTLAYSLIMLNTDLHNPNVK--KKMTLEDF 159

                           170       180       190
                    ....*....|....*....|....*....|
gi 578838189    944 IKNLRGVDNGEDIPRDLLVGIYQRIQGREL 973
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 578838189 1000 PHRRLVCCCQLYEVPDPNRPQRLGLHQREVFLFNDLLVVTKIFQKKKILVTYSFRQSFPLVEMHMQLFQNSYYQFGIKLL 1079
Cdd:cd13318     1 PHRRLVCYCRLYEVPDPNKREKPGLHQREVFLFNDLLVVTKIFSKKKSSVTYSFRQSFSLLGMQVLLFETSHYPFGIRLT 80

                          90       100       110       120       130
                  ....*....|....*....|....*....|....*....|....*....|.
gi 578838189 1080 SAVPGgerKVLIIFNAPSLQDRLRFTSDLRESIAEVQEMEKYRVESELEKQ 1130
Cdd:cd13318    81 SPLDN---KVLITFNARNESDRKKFVEDLRESILEVNEMESLRIEEELEKQ 128

N-terminal domain of Kruppel-like factors with similarity to the N-terminal domains of Kruppel-like factor (KLF)1, KLF2, and KLF4; Kruppel/Krueppel-like transcription factors (KLFs) belong to a family of proteins called the Specificity Protein (SP)/KLF family, characterized by a C-terminal DNA-binding domain of 81 amino acids consisting of three Kruppel-like C2H2 zinc fingers. These factors bind to a loose consensus motif, namely NNRCRCCYY (where N is any nucleotide; R is A/G, and Y is C/T), such as the recurring motifs in GC and GT boxes (5'-GGGGCGGGG-3' and 5-GGTGTGGGG-3') that are present in promoters and more distal regulatory elements of mammalian genes. Members of the KLF family can act as activators or repressors of transcription depending on cell and promoter context. KLFs regulate various cellular functions, such as proliferation, differentiation, and apoptosis, as well as the development and homeostasis of several types of tissue. In addition to the C-terminal DNA-binding domain, each KLF also has a unique N-terminal activation/repression domain that confers specifity and allows it to bind specifically to a certain partner, leading to distinct activities in vivo. This model represents the N-terminal domains of an unknown subfamily of KLFs, predominantly found in fish, related to the N-terminal domains of KLF1, KLF2, and KLF4.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 578838189 1350 PHRHFHAHGPVPGPQHYTLGRPGRAPRRGAGGHPQFAPHGRHPLHQPTSPLPLYSPAPQHPPAHKQGPKHF--IFSHHPQ 1427
Cdd:cd22056   209 PKHQMHSVHPQAFTHHQAAGPGALQGRGGRGGPDCHLLHSSHHHHHHHHLQYQYMNAPYPPHYAHQGAPQFhgQYSVFRE 288

                          90       100       110
                  ....*....|....*....|....*....|
gi 578838189 1428 MMPAAgaaggpgsrppggsysHPHHPQSPL 1457
Cdd:cd22056   289 PMRVH----------------HQGHPGSML 302

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 578838189   1004 LVCCCQLYEVPDPNRPQRlglHQREVFLFNDLLVvtkIFQKKKILVTYSFRQSFPLVEMHMQL---FQNSYYQFGIKLLS 1080
Cdd:smart00233    1 VIKEGWLYKKSGGGKKSW---KKRYFVLFNSTLL---YYKSKKDKKSYKPKGSIDLSGCTVREapdPDSSKKPHCFEIKT 74

                            90       100       110
                    ....*....|....*....|....*....|...
gi 578838189   1081 AvpggeRKVLIIFNAPSLQDRLRFTSDLRESIA 1113
Cdd:smart00233   75 S-----DRKTLLLQAESEEEREKWVEALRKAIA 102

Autophagy protein 16 (ATG16); Autophagy is a ubiquitous intracellular degradation system for eukaryotic cells. During autophagy, cytoplasmic components are enclosed in autophagosomes and delivered to lysosomes/vacuoles. ATG16 (also known as Apg16) has been shown to be bind to Apg5 and is required for the function of the Apg12p-Apg5p conjugate in the yeast autophagy pathway.

                           10        20        30        40
                   ....*....|....*....|....*....|....*....|..
gi 578838189    23 LLELNNIIESQQQLLETQRRRIEELEGQLDQLTQENRDLREE 64
Cdd:pfam08614   80 LVDLNEELQELEKKLREDERRLAALEAERAQLEEKLKDREEE 121