ArfGAP domain of AGFG2 (ArfGAP domain and FG repeat-containing protein 2); The ArfGAP domain and FG repeat-containing proteins (AFGF) subfamily of Arf GTPase-activating proteins consists of the two structurally-related members: AGFG1 and AGFG2. AGFG2 is a member of the HIV-1 Rev binding protein (HRB) family and contains one Arf-GAP zinc finger domain, several Phe-Gly (FG) motifs, and four Asn-Pro-Phe (NPF) motifs. AGFG2 interacts with Eps15 homology (EH) domains and plays a role in the Rev export pathway, which mediates the nucleocytoplasmic transfer of proteins and RNAs. In humans, the presence of the FG repeat motifs (11 in AGFG1 and 7 in AGFG2) are thought to be required for these proteins to act as HIV-1 Rev cofactors. Hence, AGFG promotes movement of Rev-responsive element-containing RNAs from the nuclear periphery to the cytoplasm, which is an essential step for HIV-1 replication.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 91984781  30 CRRVRELGGCSqAGNRHCFECAQRGVTYVDITVGSFVCTTCSGLLRGLNPPHRVKSISMTTFTEPEVVFLQSRGNEVCRK 109
Cdd:cd17903   1 CRRVRELGGCS-AANRHCFECAQRGVTYVDITVGSFVCTTCSGLLRGLNPPHRVKSISMTTFTEPEVLFLQARGNEVCRK 79

                        90       100       110
                ....*....|....*....|....*....|....*..
gi 91984781 110 IWLGLFDARTSLVPDSRDPQKVKEFLQEKYEKKRWYV 146
Cdd:cd17903  80 IWLGLFDARTSLIPDSRDPQKVKEFLQEKYEKKRWYV 116

ArfGAP domain of AGFG2 (ArfGAP domain and FG repeat-containing protein 2); The ArfGAP domain and FG repeat-containing proteins (AFGF) subfamily of Arf GTPase-activating proteins consists of the two structurally-related members: AGFG1 and AGFG2. AGFG2 is a member of the HIV-1 Rev binding protein (HRB) family and contains one Arf-GAP zinc finger domain, several Phe-Gly (FG) motifs, and four Asn-Pro-Phe (NPF) motifs. AGFG2 interacts with Eps15 homology (EH) domains and plays a role in the Rev export pathway, which mediates the nucleocytoplasmic transfer of proteins and RNAs. In humans, the presence of the FG repeat motifs (11 in AGFG1 and 7 in AGFG2) are thought to be required for these proteins to act as HIV-1 Rev cofactors. Hence, AGFG promotes movement of Rev-responsive element-containing RNAs from the nuclear periphery to the cytoplasm, which is an essential step for HIV-1 replication.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 91984781  30 CRRVRELGGCSqAGNRHCFECAQRGVTYVDITVGSFVCTTCSGLLRGLNPPHRVKSISMTTFTEPEVVFLQSRGNEVCRK 109
Cdd:cd17903   1 CRRVRELGGCS-AANRHCFECAQRGVTYVDITVGSFVCTTCSGLLRGLNPPHRVKSISMTTFTEPEVLFLQARGNEVCRK 79

                        90       100       110
                ....*....|....*....|....*....|....*..
gi 91984781 110 IWLGLFDARTSLVPDSRDPQKVKEFLQEKYEKKRWYV 146
Cdd:cd17903  80 IWLGLFDARTSLIPDSRDPQKVKEFLQEKYEKKRWYV 116

Putative GTPase activating protein for Arf; Putative zinc fingers with GTPase activating proteins (GAPs) towards the small GTPase, Arf. The GAP of ARD1 stimulates GTPase hydrolysis for ARD1 but not ARFs.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 91984781    31 RRVRELggCSQAGNRHCFECAQRGVTYVDITVGSFVCTTCSGLLRGL-NPPHRVKSISMTTFTEPEVVFLQSRGNEVCRK 109
Cdd:pfam01412   2 RVLREL--LKLPGNKVCADCGAPNPTWASVNLGIFICIDCSGVHRSLgVHISKVRSLTLDTWTDEQLELMKAGGNDRANE 79

                          90       100       110
                  ....*....|....*....|....*....|....*....
gi 91984781   110 IWLGLFDARtSLVPDSRDPQKVKEFLQEKYEKKRWYVPP 148
Cdd:pfam01412  80 FWEANLPPS-YKPPPSSDREKRESFIRAKYVEKKFAKPG 117

hypothetical protein; Provisional

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 91984781   44 NRHCFECAQRGVTYVDITVGSFVCTTCSGLLRGLNppHRVKSISMTTFTEPEVVFLQSRGNEVCRKIWLGLFDARTSLVP 123
Cdd:PLN03131  23 NRRCINCNSLGPQFVCTNFWTFICMTCSGIHREFT--HRVKSVSMSKFTSQDVEALQNGGNQRAREIYLKDWDQQRQRLP 100

                         90       100
                 ....*....|....*....|.
gi 91984781  124 DSRDPQKVKEFLQEKYEKKRW 144
Cdd:PLN03131 101 DNSKVDKIREFIKDIYVDKKY 121

PPE-repeat protein [Function unknown];

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 91984781 251 GQTPSQGGFANFDAFSSGP--SSSVFGSLPPAGQASFQAQPTPAGSSQGTPFGATPLAPASQPNSLADVGSFLGPGVPAA 328
Cdd:COG5651 189 GNTSSNPGFANLGLTGLNQvgIGGLNSGSGPIGLNSGPGNTGFAGTGAAAGAAAAAAAAAAAAGAGASAALASLAATLLN 268

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 91984781 329 GVPSSLFGMAGQVPPLQSVTMGGGGGSSTGLAFGAFTNPFTAPAAQSPLPSTNPFQPNGLAPGPGFGMSSAGPGFPQAVP 408
Cdd:COG5651 269 ASSLGLAATAASSAATNLGLAGSPLGLAGGGAGAAAATGLGLGAGGAAGAAGATGAGAALGAGAAAAAAGAAAGAGAAAA 348

                       170       180       190
                ....*....|....*....|....*....|....*
gi 91984781 409 PTGAFASSFPAPLFPPQTPLVQQQNGSSFGDLGSA 443
Cdd:COG5651 349 AAAGGAGGGGGGALGAGGGGGSAGAAAGAASGGGA 383

ArfGAP domain of AGFG2 (ArfGAP domain and FG repeat-containing protein 2); The ArfGAP domain and FG repeat-containing proteins (AFGF) subfamily of Arf GTPase-activating proteins consists of the two structurally-related members: AGFG1 and AGFG2. AGFG2 is a member of the HIV-1 Rev binding protein (HRB) family and contains one Arf-GAP zinc finger domain, several Phe-Gly (FG) motifs, and four Asn-Pro-Phe (NPF) motifs. AGFG2 interacts with Eps15 homology (EH) domains and plays a role in the Rev export pathway, which mediates the nucleocytoplasmic transfer of proteins and RNAs. In humans, the presence of the FG repeat motifs (11 in AGFG1 and 7 in AGFG2) are thought to be required for these proteins to act as HIV-1 Rev cofactors. Hence, AGFG promotes movement of Rev-responsive element-containing RNAs from the nuclear periphery to the cytoplasm, which is an essential step for HIV-1 replication.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 91984781  30 CRRVRELGGCSqAGNRHCFECAQRGVTYVDITVGSFVCTTCSGLLRGLNPPHRVKSISMTTFTEPEVVFLQSRGNEVCRK 109
Cdd:cd17903   1 CRRVRELGGCS-AANRHCFECAQRGVTYVDITVGSFVCTTCSGLLRGLNPPHRVKSISMTTFTEPEVLFLQARGNEVCRK 79

                        90       100       110
                ....*....|....*....|....*....|....*..
gi 91984781 110 IWLGLFDARTSLVPDSRDPQKVKEFLQEKYEKKRWYV 146
Cdd:cd17903  80 IWLGLFDARTSLIPDSRDPQKVKEFLQEKYEKKRWYV 116

ArfGAP domain of AGFG1 (ArfGAP domain and FG repeat-containing protein 1); The ArfGAP domain and FG repeat-containing proteins (AFGF) subfamily of Arf GTPase-activating proteins consists of the two structurally-related members: AGFG1 and AGFG2. AGFG1 (alias: HIV-1 Rev binding protein, HRB; Rev interacting protein, RIP; Rev/Rex activating domain-binding protein, RAB) and AGFG2 are involved in the maintenance and spread of immunodeficiency virus type 1 (HIV-1) infection. The ArfGAP domain of AGFG1 is related to nucleoporins, which is a class of proteins that mediate nucleocytoplasmic transport. AGFG1 plays a role in the Rev export pathway, which mediates the nucleocytoplasmic transfer of proteins and RNAs, possibly together by the nuclear export receptor CRM1. In humans, the presence of the FG repeat motifs (11 in AGFG1 and 7 in AGFG2) are thought to be required for these proteins to act as HIV-1 Rev cofactors. Hence, AGFG1 promotes movement of Rev-responsive element-containing RNAs from the nuclear periphery to the cytoplasm, which is an essential step for HIV-1 replication.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 91984781  31 RRVRELggCSQAGNRHCFECAQRGVTYVDITVGSFVCTTCSGLLRGLNPPHRVKSISMTTFTEPEVVFLQSRGNEVCRKI 110
Cdd:cd08857   3 KMLREM--TSLPHNRKCFDCDQRGPTYANMTVGSFVCTSCSGILRGLNPPHRVKSISMTTFTQQEIEFLQKHGNEVCKQI 80

                        90       100       110
                ....*....|....*....|....*....|....*.
gi 91984781 111 WLGLFDARTSLVPDSRDPQKVKEFLQEKYEKKRWYV 146
Cdd:cd08857  81 WLGLFDDRSSAIPDFRDPQKVKEFLQEKYEKKRWYV 116

Putative GTPase activating protein for Arf; Putative zinc fingers with GTPase activating proteins (GAPs) towards the small GTPase, Arf. The GAP of ARD1 stimulates GTPase hydrolysis for ARD1 but not ARFs.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 91984781    31 RRVRELggCSQAGNRHCFECAQRGVTYVDITVGSFVCTTCSGLLRGL-NPPHRVKSISMTTFTEPEVVFLQSRGNEVCRK 109
Cdd:pfam01412   2 RVLREL--LKLPGNKVCADCGAPNPTWASVNLGIFICIDCSGVHRSLgVHISKVRSLTLDTWTDEQLELMKAGGNDRANE 79

                          90       100       110
                  ....*....|....*....|....*....|....*....
gi 91984781   110 IWLGLFDARtSLVPDSRDPQKVKEFLQEKYEKKRWYVPP 148
Cdd:pfam01412  80 FWEANLPPS-YKPPPSSDREKRESFIRAKYVEKKFAKPG 117

GTPase-activating protein that regulates ARFs (ADP-ribosylation factors), involved in ARF-mediated vesicular transport [Intracellular trafficking and secretion];

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 91984781  40 SQAGNRHCFECAQRGVTYVDITVGSFVCTTCSGLLRGLNpPH--RVKSISMTTFTEPEVVFLQSRGNEVCRKIWL--GLF 115
Cdd:COG5347  16 SDSSNKKCADCGAPNPTWASVNLGVFLCIDCAGVHRSLG-VHisKVKSLTLDNWTEEELRRMEVGGNSNANRFYEknLLD 94

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 91984781 116 DARTSLVPDSrDPQKVKEFLQEKYEKKRWyvppdqVKGPTYTKGSASTPVQGSIPEgKPLRTLLGDPAPSLSVAAS---- 191
Cdd:COG5347  95 QLLLPIKAKY-DSSVAKKYIRKKYELKKF------IDDSSSPSDFSSFSASSTRTV-DSVDDRLDSESQSRSSSASlgns 166

                       170       180       190
                ....*....|....*....|....*....|....*
gi 91984781 192 ---------TSSQPVSQSHARTSQARSTQPPPHSS 217
Cdd:COG5347 167 nrpddelnvESFQSTGSKPRSLTSTKSNKDNLLNS 201

putative ADP-ribosylation factor GTPase-activating protein AGD14; Provisional

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 91984781   44 NRHCFECAQRGVTYVDITVGSFVCTTCSGLLRGLNppHRVKSISMTTFTEPEVVFLQSRGNEVCRKIWLGLFDARTSLVP 123
Cdd:PLN03119  23 NRRCINCNSLGPQYVCTTFWTFVCMACSGIHREFT--HRVKSVSMSKFTSKEVEVLQNGGNQRAREIYLKNWDHQRQRLP 100

                         90       100       110       120
                 ....*....|....*....|....*....|....*....|
gi 91984781  124 DSRDPQKVKEFLQEKYEKKRWYVPPDQVKGPTYTKGSAST 163
Cdd:PLN03119 101 ENSNAERVREFIKNVYVQKKYAGANDADKPSKDSQDHVSS 140

Stromal membrane-associated protein 2; a subfamily of the ArfGAP family; The SMAP subfamily of Arf GTPase-activating proteins consists of the two structurally-related members, SMAP1 and SMAP2. Each SMAP member exhibits common and distinct functions in vesicle trafficking. They both bind to clathrin heavy chain molecules and are involved in the trafficking of clathrin-coated vesicles. SMAP1 preferentially exhibits GAP toward Arf6, while SMAP2 prefers Arf1 as a substrate. SMAP1 is involved in Arf6-dependent vesicle trafficking, but not Arf6-mediated actin cytoskeleton reorganization, and regulates clathrin-dependent endocytosis of the transferrin receptors and E-cadherin. SMAP2 regulates Arf1-dependent retrograde transport of TGN38/46 from the early endosome to the trans-Golgi network (TGN). SMAP2 has the Clathrin Assembly Lymphoid Myeloid (CALM)-binding domain, but SMAP1 does not.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 91984781  44 NRHCFECAQRGVTYVDITVGSFVCTTCSGLLRGLNPP-HRVKSISMTTFTEPEVVFLQSRGNEVCRKIWlglfdarTSLV 122
Cdd:cd08859  10 NKFCADCQSKGPRWASWNIGVFICIRCAGIHRNLGVHiSRVKSVNLDQWTQEQIQCMQEMGNGKANRLY-------EAFL 82

                        90       100
                ....*....|....*....|....*
gi 91984781 123 PDS-RDPQ---KVKEFLQEKYEKKR 143
Cdd:cd08859  83 PENfRRPQtdqAVEGFIRDKYEKKK 107

Arf1 GTPase-activating protein 1; ArfGAP (ADP Ribosylation Factor GTPase Activating Protein) domain is a part of ArfGap1-like proteins that play a crucial role in controlling of membrane trafficking, particularly in the formation of COPI (coat protein complex I)-coated vesicles on Golgi membranes. The ArfGAP1 protein subfamily consists of three members: ArfGAP1 (Gcs1p in yeast), ArfGAP2 and ArfGAP3 (both are homologs of yeast Glo3p). ArfGAP2/3 are closely related, but with little similarity to ArfGAP1, except the catalytic ArfGAP domain. They promote hydrolysis of GTP bound to the small G protein ADP-ribosylation factor 1 (Arf1), which leads to the dissociation of coat proteins from Golgi-derived membranes and vesicles. Dissociation of the coat proteins is required for the fusion of these vesicles with target compartments. Thus, the GAP catalytic activity plays a key role in the formation of COPI vesicles from Golgi membrane. In contrast to ArfGAP1, which displays membrane curvature-dependent ArfGAP activity, ArfGAP2 and ArfGAP3 activities are dependent on coatomer (the core COPI complex) which required for efficient recruitment of ArfGAP2 and ArfGAP3 to the Golgi membrane. Accordingly, ArfGAP2/3 has been implicated in coatomer-mediated protein transport between the Golgi complex and the endoplasmic reticulum. Unlike ArfGAP1, which is controlled by membrane curvature through its amphipathic lipid packing sensor (ALPS) motifs, ArfGAP2/3 do not possess ALPS motif.

                        10        20        30        40        50        60        70
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|.
gi 91984781  40 SQAGNRHCFECAQRGVTYVDITVGSFVCTTCSGLLRGLNpPHR--VKSISMTTFTEPEVVFLQSRGNEVCR 108
Cdd:cd08830  10 KLPGNNRCFDCGAPNPQWASVSYGIFICLECSGVHRGLG-VHIsfVRSITMDSWSEKQLKKMELGGNAKLR 79

ArfGAP with GTPase domain, ANK repeat and PH domain 2; The AGAP subfamily of ADP-ribosylation factor GTPase-activating proteins (Arf GAPs) includes three members: AGAP1-3. In addition to the Arf GAP domain, AGAP proteins contain GTP-binding protein-like, ANK repeat and pleckstrin homology (PH) domains. AGAP1 and AGAP2 have phosphatidylinositol 4,5-bisphosphate (PI(4,5)P2)-mediated GTPase-activating protein (GAP) activity preferentially toward Arf1, and function in the endocytic system. AGAP1 and AGAP2 independently regulate AP-3 endosomes and AP-1/Rab4 fast recycling endosomes, respectively. AGAP1, via its PH domain, directly interacts with the adapter protein 3 (AP-3), which is a coat protein involved in trafficking in the endosomal-lysosomal system, and regulates AP-3-dependent trafficking. In other hand, AGAP2 specifically binds the clathrin adaptor protein AP-1 and regulates the AP-1/Rab-4 dependent endosomal trafficking. AGAP2 is overexpressed in different human cancers including prostate carcinoma and glioblastoma, and promotes cancer cell invasion. AGAP3 exists as a component of the NMDA receptor complex that regulates Arf6 and Ras/ERK signaling pathways. Moreover, AGAP3 regulates AMPA receptor trafficking through the ArfGAP domain. Together, AGAP3 is believed to involve in linking NMDA receptor activation to AMPA receptor trafficking.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 91984781  43 GNRHCFECAQRGVTYVDITVGSFVCTTCSGLLRGLNPP-HRVKSISMTTFTEPEVVFLQSRGNEVCRKIWLGLFDARTSl 121
Cdd:cd08853  12 GNSHCVDCETQNPKWASLNLGVLMCIECSGIHRNLGTHlSRVRSLDLDDWPVELRKVMSSIGNELANSIWEGSSQGQTK- 90

                        90       100
                ....*....|....*....|
gi 91984781 122 vPDSRDPQKVKE-FLQEKYE 140
Cdd:cd08853  91 -PSSDSTREEKErWIRAKYE 109

ArfGAP domain of ACAP1 (ArfGAP with Coiled-coil, ANK repeat and PH domains 1); ACAP1 belongs to the ACAP subfamily of GAPs (GTPase-activating proteins) for the small GTPase Arf (ADP-ribosylation factor). ACAP subfamily of ArfGAPs are composed of Coiled coli (BAR, Bin-Amphiphysin-Rvs), PH, ArfGAP and ANK repeats domains. ACAP1 (centaurin beta1) and ACAP2 centaurin beta2) have a GAP (GTPase-activating protein) activity preferentially toward Arf6, which regulates endocytic recycling. Both ACAP1/2 are activated by are activated by the phosphoinositides, PI(4,5)P2 and PI(3,5)P2. ACAP1 binds specifically with recycling cargo proteins such as transferrin receptor (TfR) and cellubrevin. Thus, ACAP1 promotes cargo sorting to enhance TfR recycling from the recycling endosome. In addition, phosphorylation of ACAP by Akt, a serine/threonine protein kinase, regulates the recycling of integrin beta1 to control cell migration. In contrast, ACAP2 does not exhibit a similar interaction with the recycling cargo proteins. It has been shown that ACAP2 functions both as an effector of Ras-related protein Rab35 and as an Arf6-GTPase-activating protein (GAP) during neurite outgrowth of PC12 cells. Moreover, ACAP2, together with Rab35, regulates phagocytosis in mammalian macrophages. ACAP3 also positively regulates neurite outgrowth through its GAP activity specific to Arf6 in mouse hippocampal neurons.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 91984781  43 GNRHCFECAQRGVTYVDITVGSFVCTTCSGLLRGLNpPH--RVKSISMTTFtEPEVVFLQSR-GNEVCRKIWLGLFDART 119
Cdd:cd08852  12 GNAQCCDCREPAPEWASINLGVTLCIQCSGIHRSLG-VHfsKVRSLTLDSW-EPELVKLMCElGNVIINQIYEARIEAMA 89

                        90       100
                ....*....|....*....|....*.
gi 91984781 120 SLVPDSRDPQKVKE-FLQEKYEKKRW 144
Cdd:cd08852  90 IKKPGPSSSRQEKEaWIRAKYVEKKF 115

Arf1 GTPase-activating protein 2/3-like; ArfGAP (ADP Ribosylation Factor GTPase Activating Protein) domain is a part of ArfGap1-like proteins that play a crucial role in controlling of membrane trafficking, particularly in the formation of COPI (coat protein complex I)-coated vesicles on Golgi membranes. The ArfGAP1 protein subfamily consists of three members: ArfGAP1 (Gcs1p in yeast), ArfGAP2 and ArfGAP3 (both are homologs of yeast Glo3p). ArfGAP2/3 are closely related, but with little similarity to ArfGAP1, except the catalytic ArfGAP domain. They promote hydrolysis of GTP bound to the small G protein ADP-ribosylation factor 1 (Arf1), which leads to the dissociation of coat proteins from Golgi-derived membranes and vesicles. Dissociation of the coat proteins is required for the fusion of these vesicles with target compartments. Thus, the GAP catalytic activity plays a key role in the formation of COPI vesicles from Golgi membrane. In contrast to ArfGAP1, which displays membrane curvature-dependent ArfGAP activity, ArfGAP2 and ArfGAP3 activities are dependent on coatomer (the core COPI complex) which required for efficient recruitment of ArfGAP2 and ArfGAP3 to the Golgi membrane. Accordingly, ArfGAP2/3 has been implicated in coatomer-mediated protein transport between the Golgi complex and the endoplasmic reticulum. Unlike ArfGAP1, which is controlled by membrane curvature through its amphipathic lipid packing sensor (ALPS) motifs, ArfGAP2/3 do not possess ALPS motif.

                        10        20        30        40        50        60
                ....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 91984781  40 SQAGNRHCFECAQRGVTYVDITVGSFVCTTCSGLLRGLNpPH--RVKSISMTTFTEPEVVFLQSRGNE 105
Cdd:cd08831  11 SKPENKVCFDCGAKNPTWASVTFGVFLCLDCSGVHRSLG-VHisFVRSTNLDSWTPEQLRRMKVGGNA 77

ArfGAP with GTPase domain, ANK repeat and PH domains; The AGAP subfamily of ADP-ribosylation factor GTPase-activating proteins (Arf GAPs) includes three members: AGAP1-3. In addition to the Arf GAP domain, AGAP proteins contain GTP-binding protein-like, ANK repeat and pleckstrin homology (PH) domains. AGAP1 and AGAP2 have phosphatidylinositol 4,5-bisphosphate (PI(4,5)P2)-mediated GTPase-activating protein (GAP) activity preferentially toward Arf1, and function in the endocytic system. AGAP1 and AGAP2 independently regulate AP-3 endosomes and AP-1/Rab4 fast recycling endosomes, respectively. AGAP1, via its PH domain, directly interacts with the adapter protein 3 (AP-3), which is a coat protein involved in trafficking in the endosomal-lysosomal system, and regulates AP-3-dependent trafficking. In other hand, AGAP2 specifically binds the clathrin adaptor protein AP-1 and regulates the AP-1/Rab-4 dependent endosomal trafficking. AGAP2 is overexpressed in different human cancers including prostate carcinoma and glioblastoma, and promotes cancer cell invasion. AGAP3 exists as a component of the NMDA receptor complex that regulates Arf6 and Ras/ERK signaling pathways. Moreover, AGAP3 regulates AMPA receptor trafficking through the ArfGAP domain. Together, AGAP3 is believed to involve in linking NMDA receptor activation to AMPA receptor trafficking.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 91984781  42 AGNRHCFECAQRGVTYVDITVGSFVCTTCSGLLRGLNPpH--RVKSISMTTFTEPEVVFLQSRGNEVCRKIWLGLFDART 119
Cdd:cd08836  10 RGNDHCVDCGAPNPDWASLNLGALMCIECSGIHRNLGT-HisRVRSLDLDDWPVELLKVMSAIGNDLANSVWEGNTQGRT 88

                        90       100
                ....*....|....*....|..
gi 91984781 120 SLVPDSrdPQKVKE-FLQEKYE 140
Cdd:cd08836  89 KPTPDS--SREEKErWIRAKYE 108

ArfGAP domain of ASAP (Arf GAP, SH3, ANK repeat and PH domains) subfamily of ADP-ribosylation factor GTPase-activating proteins; The ArfGAPs are a family of multidomain proteins with a common catalytic domain that promotes the hydrolysis of GTP bound to Arf, thereby inactivating Arf signaling. ASAP-subfamily GAPs include three members: ASAP1, ASAP2, ASAP3. The ASAP subfamily comprises Arf GAP, SH3, ANK repeat and PH domains. From the N-terminus, each member has a BAR, PH, Arf GAP, ANK repeat, and proline rich domains. Unlike ASAP3, ASAP1 and ASAP2 also have an SH3 domain at the C-terminus. ASAP1 and ASAP2 show strong GTPase-activating protein (GAP) activity toward Arf1 and Arf5 and weak activity toward Arf6. ASAP1 is a target of Src and FAK signaling that regulates focal adhesions, circular dorsal ruffles (CDR), invadopodia, and podosomes. ASAP1 GAP activity is synergistically stimulated by phosphatidylinositol 4,5-bisphosphate (PIP2) and phosphatidic acid. ASAP2 is believed to function as an ArfGAP that controls ARF-mediated vesicle budding when recruited to Golgi membranes. It also functions as a substrate and downstream target for protein tyrosine kinases Pyk2 and Src, a pathway that may be involved in the regulation of vesicular transport. ASAP3 is a focal adhesion-associated ArfGAP that functions in cell migration and invasion. Similar to ASAP1, the GAP activity of ASAP3 is strongly enhanced by PIP2 via PH domain. Like ASAP1, ASAP3 associates with focal adhesions and circular dorsal ruffles. However, unlike ASAP1, ASAP3 does not localize to invadopodia or podosomes. Both ASAP 1 and 3 have been implicated in oncogenesis, as ASAP1 is highly expressed in metastatic breast cancer and ASAP3 in hepatocellular carcinoma.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 91984781  43 GNRHCFECAQRGVTYVDITVGSFVCTTCSGLLRGLNPPH-RVKSISMTTFTEPEVVFLQSRGNEVCRKIWLGLFDARTSL 121
Cdd:cd08834  14 GNDVCCDCGSPDPTWLSTNLGILTCIECSGVHRELGVHVsRIQSLTLDNLGTSELLLARNLGNEGFNEIMEANLPPGYKP 93

                        90       100
                ....*....|....*....|..
gi 91984781 122 VPDSRDPQKvKEFLQEKYEKKR 143
Cdd:cd08834  94 TPNSDMEER-KDFIRAKYVEKK 114

ArfGap with Rho-Gap domain, ANK repeat and PH domain-containing protein 3; The ARAP subfamily includes three members, ARAP1-3, and belongs to the ADP-ribosylation factor GTPase-activating proteins (Arf GAPs) family of proteins that promotes the hydrolysis of GTP bound to Arf, thereby inactivating Arf signaling. The function of Arfs is dependent on GAPs and guanine nucleotide exchange factors (GEFs), which allow Arfs to cycle between the GDP-bound and GTP-bound forms. In addition to the Arf GAP domain, ARAPs contain the SAM (sterile-alpha motif) domain, 5 pleckstrin homology (PH) domains, the Rho-GAP domain, the Ras-association domain, and ANK repeats. ARAPs show phosphatidylinositol 3,4,5-trisphosphate (PI(3,4,5)P3)-dependent GAP activity toward Arf6. ARAPs play important roles in endocytic trafficking, cytoskeleton reorganization in response to growth factors stimulation, and focal adhesion dynamics. ARAP3 possesses a unique dual-specificity GAP activity for Arf6 and RhoA regulated by PI(3,4,5)P3 and a small GTPase Rap1-GTP. The RhoGAP activity of ARAP3 is enhanced by direct binding of Rap1-GTP to the Ras-association (RA) domain. ARAP3 is involved in regulation of cell shape and adhesion.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 91984781  23 EAASEVWcrrvrelggcSQAGNRHCFECAQRGVTYVDITVGSFVCTTCSGLLRGLNPP-HRVKSISM-TTFTEPEVVFL- 99
Cdd:cd17902   2 EVAEKIW----------SNKANRFCADCHASSPDWASINLCVVICKQCAGQHRSLGSGiSKVQSLKLdTSVWSNEIVQLf 71

                        90       100       110       120
                ....*....|....*....|....*....|....*....|....*
gi 91984781 100 QSRGNEVCRKIWLGLFDARTSLVPDSrDPQKVKEFLQEKYEKKRW 144
Cdd:cd17902  72 IVLGNDRANRFWAARLPASEALHPDA-TPEQRREFISRKYREGRF 115

ArfGAP domain of ACAP2 (ArfGAP with Coiled-coil, ANK repeat and PH domains 2); ACAP2 belongs to the ACAP subfamily of GAPs (GTPase-activating proteins) for the small GTPase Arf (ADP-ribosylation factor). ACAP subfamily of ArfGAPs are composed of Coiled coli (BAR, Bin-Amphiphysin-Rvs), PH, ArfGAP and ANK repeats domains. ACAP1 (centaurin beta1) and ACAP2 centaurin beta2) have a GAP (GTPase-activating protein) activity preferentially toward Arf6, which regulates endocytic recycling. Both ACAP1/2 are activated by are activated by the phosphoinositides, PI(4,5)P2 and PI(3,5)P2. ACAP1 binds specifically with recycling cargo proteins such as transferrin receptor (TfR) and cellubrevin. Thus, ACAP1 promotes cargo sorting to enhance TfR recycling from the recycling endosome. In addition, phosphorylation of ACAP by Akt, a serine/threonine protein kinase, regulates the recycling of integrin beta1 to control cell migration. In contrast, ACAP2 does not exhibit a similar interaction with the recycling cargo proteins. It has been shown that ACAP2 functions both as an effector of Ras-related protein Rab35 and as an Arf6-GTPase-activating protein (GAP) during neurite outgrowth of PC12 cells. Moreover, ACAP2, together with Rab35, regulates phagocytosis in mammalian macrophages. ACAP3 also positively regulates neurite outgrowth through its GAP activity specific to Arf6 in mouse hippocampal neurons.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 91984781  43 GNRHCFECAQRGVTYVDITVGSFVCTTCSGLLRGLNPP-HRVKSISMTTFtEPEVVFLQSR-GNEVCRKIWLGLFDARTS 120
Cdd:cd08851  12 GNASCCDCGLADPRWASINLGITLCIECSGIHRSLGVHfSKVRSLTLDTW-EPELLKLMCElGNDVINRIYEARVEKMGA 90

                        90       100
                ....*....|....*....|....*.
gi 91984781 121 LVPDSRDPQKVKE-FLQEKY-EKKRW 144
Cdd:cd08851  91 KKPQPGGQRQEKEaYIRAKYvERKFV 116

ArfGAP domain of ASAP2 (ArfGAP2 with SH3 domain, ANK repeat and PH domain-containing protein 2); The Arf GAPs are a family of multidomain proteins with a common catalytic domain that promotes the hydrolysis of GTP bound to Arf , thereby inactivating Arf signaling. ASAP-subfamily GAPs include three members: ASAP1, ASAP2, ASAP3. The ASAP subfamily comprises Arf GAP, SH3, ANK repeat and PH domains. From the N-terminus, each member has a BAR, PH, Arf GAP, ANK repeat, and proline rich domains. Unlike ASAP3, ASAP1 and ASAP2 also have an SH3 domain at the C-terminus. ASAP1 and ASAP2 show strong GTPase-activating protein (GAP) activity toward Arf1 and Arf5 and weak activity toward Arf6. ASAP1 is a target of Src and FAK signaling that regulates focal adhesions, circular dorsal ruffles (CDR), invadopodia, and podosomes. ASAP1 GAP activity is synergistically stimulated by phosphatidylinositol 4,5-bisphosphate (PIP2) and phosphatidic acid. ASAP2 is believed to function as an ArfGAP that controls ARF-mediated vesicle budding when recruited to Golgi membranes. It also functions as a substrate and downstream target for protein tyrosine kinases Pyk2 and Src, a pathway that may be involved in the regulation of vesicular transport.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 91984781  42 AGNRHCFECAQRGVTYVDITVGSFVCTTCSGLLRGLNPPH-RVKSISMTTFTEPEVVFLQSRGNEVCRKIWLGLFDARTS 120
Cdd:cd08849  13 TGNDVCCDCGAPDPTWLSTNLGILTCIECSGIHRELGVHYsRMQSLTLDVLGTSELLLAKNIGNAGFNEIMEACLPAEDV 92

                        90       100
                ....*....|....*....|....*
gi 91984781 121 LVPD-SRDPQKVKEFLQEKYEKKRW 144
Cdd:cd08849  93 VKPNpGSDMNARKDYITAKYIERRY 117

ArfGap with Rho-Gap domain, ANK repeat and PH domain-containing protein 1; The ARAP subfamily includes three members, ARAP1-3, and belongs to the ADP-ribosylation factor GTPase-activating proteins (Arf GAPs) family of proteins that promotes the hydrolysis of GTP bound to Arf, thereby inactivating Arf signaling. The function of Arfs is dependent on GAPs and guanine nucleotide exchange factors (GEFs), which allow Arfs to cycle between the GDP-bound and GTP-bound forms. In addition to the Arf GAP domain, ARAPs contain the SAM (sterile-alpha motif) domain, 5 pleckstrin homology (PH) domains, the Rho-GAP domain, the Ras-association domain, and ANK repeats. ARAPs show phosphatidylinositol 3,4,5-trisphosphate (PI(3,4,5)P3)-dependent GAP activity toward Arf6. ARAPs play important roles in endocytic trafficking, cytoskeleton reorganization in response to growth factors stimulation, and focal adhesion dynamics. ARAP1 localizes to the plasma membrane, the Golgi complex, and endosomal compartments. It displays PI(3,4,5)P3-dependent ArfGAP activity that regulates Arf-, RhoA-, and Cdc42-dependent cellular events. For example, ARAP1 inhibits the trafficking of epidermal growth factor receptor (EGFR) to the early endosome.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 91984781  40 SQAGNRHCFECAQRGVTYVDITVGSFVCTTCSGLLRGLNPP-HRVKSISM--TTFTEPEVVFLQSRGNEVCRKIWLGLFD 116
Cdd:cd17901   9 SVESNRFCADCGSPKPDWASVNLCVVICKRCAGEHRGLGPSvSKVRSLKMdrKVWTEELIELFLLLGNGKANQFWAANVP 88

                        90       100
                ....*....|....*....|....*...
gi 91984781 117 ARTSLVPDSrDPQKVKEFLQEKYEKKRW 144
Cdd:cd17901  89 PSEALCPSS-SSEERRHFITAKYKEGKY 115

Arf1 GTPase-activating protein 2; ArfGAP (ADP Ribosylation Factor GTPase Activating Protein) domain is a part of ArfGap1-like proteins that play a crucial role in controlling of membrane trafficking, particularly in the formation of COPI (coat protein complex I)-coated vesicles on Golgi membranes. The ArfGAP1 protein subfamily consists of three members: ArfGAP1 (Gcs1p in yeast), ArfGAP2 and ArfGAP3 (both are homologs of yeast Glo3p). ArfGAP2/3 are closely related, but with little similarity to ArfGAP1, except the catalytic ArfGAP domain. They promote hydrolysis of GTP bound to the small G protein ADP-ribosylation factor 1 (Arf1), which leads to the dissociation of coat proteins from Golgi-derived membranes and vesicles. Dissociation of the coat proteins is required for the fusion of these vesicles with target compartments. Thus, the GAP catalytic activity plays a key role in the formation of COPI vesicles from Golgi membrane. In contrast to ArfGAP1, which displays membrane curvature-dependent ArfGAP activity, ArfGAP2 and ArfGAP3 activities are dependent on coatomer (the core COPI complex) which required for efficient recruitment of ArfGAP2 and ArfGAP3 to the Golgi membrane. Accordingly, ArfGAP2/3 has been implicated in coatomer-mediated protein transport between the Golgi complex and the endoplasmic reticulum. Unlike ArfGAP1, which is controlled by membrane curvature through its amphipathic lipid packing sensor (ALPS) motifs, ArfGAP2/3 do not possess ALPS motif.

                        10        20        30
                ....*....|....*....|....*....|....
gi 91984781  44 NRHCFECAQRGVTYVDITVGSFVCTTCSGLLRGL 77
Cdd:cd09029  19 NKACFDCGAKNPSWASITYGVFLCIDCSGVHRSL 52

Arf1 GTPase-activating protein 3; ArfGAP (ADP Ribosylation Factor GTPase Activating Protein) domain is a part of ArfGap1-like proteins that play a crucial role in controlling of membrane trafficking, particularly in the formation of COPI (coat protein complex I)-coated vesicles on Golgi membranes. The ArfGAP1 protein subfamily consists of three members: ArfGAP1 (Gcs1p in yeast), ArfGAP2 and ArfGAP3 (both are homologs of yeast Glo3p). ArfGAP2/3 are closely related, but with little similarity to ArfGAP1, except the catalytic ArfGAP domain. They promote hydrolysis of GTP bound to the small G protein ADP-ribosylation factor 1 (Arf1), which leads to the dissociation of coat proteins from Golgi-derived membranes and vesicles. Dissociation of the coat proteins is required for the fusion of these vesicles with target compartments. Thus, the GAP catalytic activity plays a key role in the formation of COPI vesicles from Golgi membrane. In contrast to ArfGAP1, which displays membrane curvature-dependent ArfGAP activity, ArfGAP2 and ArfGAP3 activities are dependent on coatomer (the core COPI complex) which required for efficient recruitment of ArfGAP2 and ArfGAP3 to the Golgi membrane. Accordingly, ArfGAP2/3 has been implicated in coatomer-mediated protein transport between the Golgi complex and the endoplasmic reticulum. Unlike ArfGAP1, which is controlled by membrane curvature through its amphipathic lipid packing sensor (ALPS) motifs, ArfGAP2/3 do not possess ALPS motif.

                        10        20        30        40
                ....*....|....*....|....*....|....*....|....*..
gi 91984781  31 RRVRelggcSQAGNRHCFECAQRGVTYVDITVGSFVCTTCSGLLRGL 77
Cdd:cd09028  11 KRLR-----SVPTNKVCFDCGAKNPSWASITYGVFLCIDCSGIHRSL 52

ArfGAP domain of ASAP3 (ArfGAP with ANK repeat and PH domain-containing protein 3); The ArfGAPs are a family of multidomain proteins with a common catalytic domain that promotes the hydrolysis of GTP bound to Arf, thereby inactivating Arf signaling. ASAP-subfamily GAPs include three members: ASAP1, ASAP2, ASAP3. The ASAP subfamily comprises Arf GAP, SH3, ANK repeat and PH domains. From the N-terminus, each member has a BAR, PH, Arf GAP, ANK repeat, and proline rich domains. Unlike ASAP1 and ASAP2, ASAP3 do not have an SH3 domain at the C-terminus. ASAP1 and ASAP2 show strong GTPase-activating protein (GAP) activity toward Arf1 and Arf5 and weak activity toward Arf6. ASAP1 is a target of Src and FAK signaling that regulates focal adhesions, circular dorsal ruffles (CDR), invadopodia, and podosomes. ASAP1 GAP activity is synergistically stimulated by phosphatidylinositol 4,5-bisphosphate (PIP2) and phosphatidic acid. ASAP2 is believed to function as an ArfGAP that controls ARF-mediated vesicle budding when recruited to Golgi membranes. It also functions as a substrate and downstream target for protein tyrosine kinases Pyk2 and Src, a pathway that may be involved in the regulation of vesicular transport. ASAP3 is a focal adhesion-associated ArfGAP that functions in cell migration and invasion. Similar to ASAP1, the GAP activity of ASAP3 is strongly enhanced by PIP2 via PH domain. Like ASAP1, ASAP3 associates with focal adhesions and circular dorsal ruffles. However, unlike ASAP1, ASAP3 does not localize to invadopodia or podosomes. ASAP 1 and 3 have been implicated in oncogenesis, as ASAP1 is highly expressed in metastatic breast cancer and ASAP3 in hepatocellular carcinoma.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 91984781  40 SQAGNRHCFECAQRGVTYVDITVGSFVCTTCSGLLRGLNPPH-RVKSISMTTFTEPEVVFLQSRGNEVCRKIWLGLFDAR 118
Cdd:cd17900  11 SRPGNSQCCDCGAPDPTWLSTNLGILTCIECSGIHRELGVRYsRIQSLTLDLLSTSELLLAVSMGNTRFNEVMEATLPAH 90

                        90       100
                ....*....|....*....|....*..
gi 91984781 119 TSLVPDSR-DPQKVKEFLQEKYEKKRW 144
Cdd:cd17900  91 GGPKPSAEsDMGTRKDYIMAKYVEHRF 117

The GIT subfamily of ADP-ribosylation factor GTPase-activating proteins; The GIT (G-protein coupled receptor kinase-interacting protein) subfamily includes GIT1 and GIT2, which have three ANK repeats, a Spa-homology domain (SHD), a coiled-coil domain and a C-terminal paxillin-binding site (PBS). The GIT1/2 proteins are GTPase-activating proteins that function as an inactivator of Arf signaling, and interact with the PIX/Cool family of Rac/Cdc42 guanine nucleotide exchange factors (GEFs). Unlike other ArfGAPs, GIT and PIX (Pak-interacting exchange factor) proteins are tightly associated to form an oligomeric complex that acts as a scaffold and signal integrator that can be recruited for multiple signaling pathways. The GIT/PIX complex functions as a signaling scaffold by binding to specific protein partners. As a result, the complex is transported to specific cellular locations. For instance, the GIT partners paxillin or integrin-alpha4 (to focal adhesions), piccolo and liprin-alpha (to synapses), and the beta-PIX partner Scribble (to epithelial cell-cell contacts and synapses). Moreover, the GIT/PIT complex functions to integrate signals from multiple GTP-binding protein and protein kinase pathways to regulate the actin cytoskeleton and thus cell polarity, adhesion and migration.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 91984781  44 NRHCFECAQRGVTYVDITVGSFVCTTCSGLLRGLNPP-HRVKSISMTTFTEPEVVFLQSRGNEVCRKIW-LGLFDARTSL 121
Cdd:cd08833   8 ARVCADCSAPDPEWASINRGVLICDECCSIHRSLGRHiSQVKSLRKDQWPPSLLEMVQTLGNNGANSIWeHSLLDPSQSG 87

                        90       100
                ....*....|....*....|...
gi 91984781 122 V-----PDSRDPQKvKEFLQEKY 139
Cdd:cd08833  88 KrkpipPDPVHPTK-EEFIKAKY 109