GIT2 GTPase activating protein for Arf; 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 1720413633   1 MSKRLRSSDVCADCNGPDPSWASVNRGTFICDECCSVHRSLGRHISQVRHLKHTAWPPTLLQMVETLYNNGANSIWEHSL 80
Cdd:cd08847     1 MSKRLRSSEVCADCSTSDPRWASVNRGVLICDECCSVHRSLGRHISQVRHLKHTSWPPTLLQMVQTLYNNGANSIWEHSL 80

                          90       100       110
                  ....*....|....*....|....*....|.
gi 1720413633  81 LDPASIMSGRRKANPQDKVHPNKAEFIRAKY 111
Cdd:cd08847    81 LDPASIMSGKRKANPQDKVHPNKAEFIRAKY 111

GIT coiled-coil Rho guanine nucleotide exchange factor; GIT-CC is the coiled-coil region of GIT (G protein-coupled receptor kinase-interacting) proteins. This coiled-coil region is the surface that associates with the equivalent binding-region on beta-PIX, or p21-activated kinase-interacting exchange factor proteins. Both GIT and PIX complex together to form a scaffold for the formation of multi-protein assemblies. On its own the GIT-CC region assembles into a parallel two-stranded CC in the asymmetric unit. Similarly the PIX coiled-coil region assembles into a trimer. At least in vitro the two regions associate together into a stable heteropentameric complex that consists of one PIX trimer and one GIT dimer.

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 1720413633 416 KSLDS-DLSDGPVTVQEFMEVKSALVASEAKRQQLMK---------------LQTLQSENSSLRRQ 465
Cdd:pfam16559   1 KSLDSsDLSDGPVTVQEYLELKEALAASEAKIQQLMKvntnlsdelrllqskVQTLQQENADLRDQ 66

Spa2 homology domain (SHD) of GIT; GIT proteins are signaling integrators with GTPase-activating function which may be involved in the organization of the cytoskeletal matrix assembled at active zones (CAZ). The function of the CAZ might be to define sites of neurotransmitter release. Mutations in the Spa2 homology domain (SHD) domain of GIT1 described here interfere with the association of GIT1 with Piccolo, beta-PIX, and focal adhesion kinase.

                          10        20
                  ....*....|....*....|....*....
gi 1720413633 268 AKKKLQSLSNHLFEELAMDVYDEVDRRET 296
Cdd:pfam08518   1 ARQKLARLSNQQFEELVTDVYDELDRRQT 29

GIT2 GTPase activating protein for Arf; 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 1720413633   1 MSKRLRSSDVCADCNGPDPSWASVNRGTFICDECCSVHRSLGRHISQVRHLKHTAWPPTLLQMVETLYNNGANSIWEHSL 80
Cdd:cd08847     1 MSKRLRSSEVCADCSTSDPRWASVNRGVLICDECCSVHRSLGRHISQVRHLKHTSWPPTLLQMVQTLYNNGANSIWEHSL 80

                          90       100       110
                  ....*....|....*....|....*....|.
gi 1720413633  81 LDPASIMSGRRKANPQDKVHPNKAEFIRAKY 111
Cdd:cd08847    81 LDPASIMSGKRKANPQDKVHPNKAEFIRAKY 111

G protein-coupled receptor kinase-interacting protein 1 C term; This domain family is found in eukaryotes, and is approximately 120 amino acids in length. The family is found in association with pfam01412, pfam00023, pfam08518. GIT1 plays an important role in cell adhesion, motility, cytoskeletal remodelling and membrane trafficking. To perform this function, it localizes p21-activated kinase (PAK) and PAK-interactive exchange factor to focal adhesions. Its activation is regulated by interaction between its paxillin-binding C terminal and the LD motifs of paxillin. The C terminal folds into a four helix bundle.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1720413633 598 EDVIRKTEQITKNIQELLRAAQENKHDSYIPCSERIHVAVTEMAALFPKKPKSDTVRTSLRLLTSSAYRLQSECrkalpG 677
Cdd:pfam12205   2 DNVVRQTELITKAIQELLKAAQEGRHSEFLDCAERIRSAVTEMAALFPKSPRSETVREALKALTDAADKLQAEC-----V 76

                          90       100       110
                  ....*....|....*....|....*....|....
gi 1720413633 678 DSSLPTDVQLVTQQVIQCAYDIAKAAKQLVTITT 711
Cdd:pfam12205  77 SLKASPGPDDSSQEIITAAYDIAKAAKELVTLFE 110

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 1720413633   3 KRLRSSDVCADCNGPDPSWASVNRGTFICDECCSVHRSLGRHISQVRHLKHTAWPPTLLQMVETLYNNGANSIWEHSLLD 82
Cdd:COG5347    15 KSDSSNKKCADCGAPNPTWASVNLGVFLCIDCAGVHRSLGVHISKVKSLTLDNWTEEELRRMEVGGNSNANRFYEKNLLD 94

                          90       100       110       120       130       140
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 1720413633  83 PASImsgrrkanPQDKVHPNK--AEFIRAKYQMLAFVHRLPCREDDSVTAKDlSKQLHSSVRTGN 145
Cdd:COG5347    95 QLLL--------PIKAKYDSSvaKKYIRKKYELKKFIDDSSSPSDFSSFSAS-STRTVDSVDDRL 150

Ankyrin repeat [Signal transduction mechanisms];

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1720413633 137 LHSSVRTGNLETCLRLLSLGAQANFFHPEkGSTPLHVASKAGQILQAELLAVYGADPGTQDSSGKTPVDYARQGGHHELA 216
Cdd:COG0666   157 LHLAAANGNLEIVKLLLEAGADVNARDND-GETPLHLAAENGHLEIVKLLLEAGADVNAKDNDGKTALDLAAENGNLEIV 235

                  ....*
gi 1720413633 217 ERLIE 221
Cdd:COG0666   236 KLLLE 240

Spa2 homology domain (SHD) of GIT; GIT proteins are signaling integrators with GTPase-activating function which may be involved in the organization of the cytoskeletal matrix assembled at active zones (CAZ). The function of the CAZ might be to define sites of neurotransmitter release. Mutations in the Spa2 homology domain (SHD) domain of GIT1 described here interfere with the association of GIT1 with Piccolo, beta-PIX, and focal adhesion kinase.

                          10        20
                  ....*....|....*....|....*....
gi 1720413633 268 AKKKLQSLSNHLFEELAMDVYDEVDRRET 296
Cdd:pfam08518   1 ARQKLARLSNQQFEELVTDVYDELDRRQT 29

Spa2 homology domain (SHD) of GIT; GIT proteins are signaling integrators with GTPase-activating function which may be involved in the organization of the cytoskeletal matrix assembled at active zones (CAZ). The function of the CAZ might be to define sites of neurotransmitter release. Mutations in the Spa2 homology domain (SHD) domain of GIT1 described here interfere with the association of GIT1 with Piccolo, beta-PIX, and focal adhesion kinase.

                          10        20
                  ....*....|....*....|....*....
gi 1720413633 332 GRQKLARFNAHEFATLVIDILSDAKRRQQ 360
Cdd:pfam08518   1 ARQKLARLSNQQFEELVTDVYDELDRRQT 29

6-phosphofructo-2-kinase/fructose-2,6-biphosphatase; Provisional

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1720413633 118 HRLPCRED-DSVTAKDLSKQLHSSVRTGNLETCLRLLSLGAQANF--FHpekGSTPLHVASKAGQILQAELLAVYGADPG 194
Cdd:PTZ00322   66 HNLTTEEViDPVVAHMLTVELCQLAASGDAVGARILLTGGADPNCrdYD---GRTPLHIACANGHVQVVRVLLEFGADPT 142

                          90       100
                  ....*....|....*....|....*
gi 1720413633 195 TQDSSGKTPVDYARQGGHHELAERL 219
Cdd:PTZ00322  143 LLDKDGKTPLELAEENGFREVVQLL 167

GIT2 GTPase activating protein for Arf; 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 1720413633   1 MSKRLRSSDVCADCNGPDPSWASVNRGTFICDECCSVHRSLGRHISQVRHLKHTAWPPTLLQMVETLYNNGANSIWEHSL 80
Cdd:cd08847     1 MSKRLRSSEVCADCSTSDPRWASVNRGVLICDECCSVHRSLGRHISQVRHLKHTSWPPTLLQMVQTLYNNGANSIWEHSL 80

                          90       100       110
                  ....*....|....*....|....*....|.
gi 1720413633  81 LDPASIMSGRRKANPQDKVHPNKAEFIRAKY 111
Cdd:cd08847    81 LDPASIMSGKRKANPQDKVHPNKAEFIRAKY 111

GIT1 GTPase activating protein for Arf; 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 1720413633   1 MSKRLRSSDVCADCNGPDPSWASVNRGTFICDECCSVHRSLGRHISQVRHLKHTAWPPTLLQMVETLYNNGANSIWEHSL 80
Cdd:cd08846     1 MSRKGPRAEVCADCSAPDPGWASINRGVLICDECCSVHRSLGRHISIVKHLRHSAWPPTLLQMVHTLASNGANSIWEHSL 80

                          90       100       110
                  ....*....|....*....|....*....|.
gi 1720413633  81 LDPASIMSGRRKANPQDKVHPNKAEFIRAKY 111
Cdd:cd08846    81 LDPAQVQSGRRKANPQDKVHPTKSEFIRAKY 111

G protein-coupled receptor kinase-interacting protein 1 C term; This domain family is found in eukaryotes, and is approximately 120 amino acids in length. The family is found in association with pfam01412, pfam00023, pfam08518. GIT1 plays an important role in cell adhesion, motility, cytoskeletal remodelling and membrane trafficking. To perform this function, it localizes p21-activated kinase (PAK) and PAK-interactive exchange factor to focal adhesions. Its activation is regulated by interaction between its paxillin-binding C terminal and the LD motifs of paxillin. The C terminal folds into a four helix bundle.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1720413633 598 EDVIRKTEQITKNIQELLRAAQENKHDSYIPCSERIHVAVTEMAALFPKKPKSDTVRTSLRLLTSSAYRLQSECrkalpG 677
Cdd:pfam12205   2 DNVVRQTELITKAIQELLKAAQEGRHSEFLDCAERIRSAVTEMAALFPKSPRSETVREALKALTDAADKLQAEC-----V 76

                          90       100       110
                  ....*....|....*....|....*....|....
gi 1720413633 678 DSSLPTDVQLVTQQVIQCAYDIAKAAKQLVTITT 711
Cdd:pfam12205  77 SLKASPGPDDSSQEIITAAYDIAKAAKELVTLFE 110

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 1720413633   1 MSKRLR---SSDVCADCNGPDPSWASVNRGTFICDECCSVHRSLGRHISQVRHLKHTAWPPTLLQMVETLYNNGANSIWE 77
Cdd:pfam01412   3 VLRELLklpGNKVCADCGAPNPTWASVNLGIFICIDCSGVHRSLGVHISKVRSLTLDTWTDEQLELMKAGGNDRANEFWE 82

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|..
gi 1720413633  78 HSLLDPASImsgrrkanPQDKVHPNKAEFIRAKYQMLAFVHR 119
Cdd:pfam01412  83 ANLPPSYKP--------PPSSDREKRESFIRAKYVEKKFAKP 116

ArfGAP domain of ACAP (ArfGAP with Coiled-coil, ANK repeat and PH domains) proteins; ArfGAP domain is an essential part of ACAP proteins that play important role in endocytosis, actin remodeling and receptor tyrosine kinase-dependent cell movement. ACAP subfamily of ArfGAPs are composed of coiled coils (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. In addition, 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 1720413633   9 DVCADCNGPDPSWASVNRGTFICDECCSVHRSLGRHISQVRHLKHTAWPPTLLQMVETLYNNGANSIWEHSLLDpasimS 88
Cdd:cd08835    14 AQCCDCGSPDPRWASINLGVTLCIECSGIHRSLGVHVSKVRSLTLDSWEPELLKVMLELGNDVVNRIYEANVPD-----D 88

                          90       100
                  ....*....|....*....|....*....
gi 1720413633  89 GRRKANPqDKVHPNKAEFIRAKYQMLAFV 117
Cdd:cd08835    89 GSVKPTP-DSSRQEREAWIRAKYVEKKFV 116

ArfGAP with GTPase domain, ANK repeat and PH domain 3; 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. 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. 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.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1720413633   3 KRLRSSDVCADCNGPDPSWASVNRGTFICDECCSVHRSLGRHISQVRHLKHTAWPPTLLQMVETLYNNGANSIWEHSLld 82
Cdd:cd08855     9 RNVRGNSFCIDCDAPNPDWASLNLGALMCIECSGIHRNLGTHLSRVRSLDLDDWPVELSMVMTAIGNAMANSVWEGAL-- 86

                          90       100       110
                  ....*....|....*....|....*....|
gi 1720413633  83 pasimSGRRKANPqDKVHPNKAEFIRAKYQ 112
Cdd:cd08855    87 -----DGYSKPGP-DSTREEKERWIRAKYE 110

ArfGAP with GTPase domain, ANK repeat and PH domain 1; 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 1720413633   6 RSSDVCADCNGPDPSWASVNRGTFICDECCSVHRSLGRHISQVRHLKHTAWPPTLLQMVETLYNNGANSIWEhslldpaS 85
Cdd:cd08854    11 KGNSLCVDCGAPNPTWASLNLGALICIECSGIHRNLGTHLSRVRSLDLDDWPRELTLVLTAIGNHMANSIWE-------S 83

                          90       100
                  ....*....|....*....|....*..
gi 1720413633  86 IMSGRRKANPqDKVHPNKAEFIRAKYQ 112
Cdd:cd08854    84 CTQGRTKPAP-DSSREERESWIRAKYE 109

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 1720413633   3 KRLRSSDVCADCNGPDPSWASVNRGTFICDECCSVHRSLGRHISQVRHLKHTAWPPTLLQMVETLYNNGANSIWEHSlld 82
Cdd:cd08853     8 RNMRGNSHCVDCETQNPKWASLNLGVLMCIECSGIHRNLGTHLSRVRSLDLDDWPVELRKVMSSIGNELANSIWEGS--- 84

                          90       100       110
                  ....*....|....*....|....*....|
gi 1720413633  83 pasiMSGRRKANpQDKVHPNKAEFIRAKYQ 112
Cdd:cd08853    85 ----SQGQTKPS-SDSTREEKERWIRAKYE 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 1720413633  11 CADCNGPDPSWASVNRGTFICDECCSVHRSLGRHISQVRHLKHTAWPPTLLQMVETLYNNGANSIWEhSLLDPASImsgr 90
Cdd:cd08852    16 CCDCREPAPEWASINLGVTLCIQCSGIHRSLGVHFSKVRSLTLDSWEPELVKLMCELGNVIINQIYE-ARIEAMAI---- 90

                          90       100       110
                  ....*....|....*....|....*....|.
gi 1720413633  91 RKANPQDKvHPNKAEFIRAKYQMLAFVHRLP 121
Cdd:cd08852    91 KKPGPSSS-RQEKEAWIRAKYVEKKFITKLP 120

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 1720413633  11 CADCNGPDPSWASVNRGTFICDECCSVHRSLGRHISQVRHLKHTAWPPTLLQMVETLYNNGANSIWEHSLLDpasimSGR 90
Cdd:cd08851    16 CCDCGLADPRWASINLGITLCIECSGIHRSLGVHFSKVRSLTLDTWEPELLKLMCELGNDVINRIYEARVEK-----MGA 90

                          90       100
                  ....*....|....*....|....*..
gi 1720413633  91 RKANPQDKVHPNKAeFIRAKYQMLAFV 117
Cdd:cd08851    91 KKPQPGGQRQEKEA-YIRAKYVERKFV 116

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 1720413633   3 KRLRSSDVCADCNGPDPSWASVNRGTFICDECCSVHRSLGRHISQVRHLKHTAWPPTLLQMVETLYNNGANSIWEHSLLD 82
Cdd:COG5347    15 KSDSSNKKCADCGAPNPTWASVNLGVFLCIDCAGVHRSLGVHISKVKSLTLDNWTEEELRRMEVGGNSNANRFYEKNLLD 94

                          90       100       110       120       130       140
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 1720413633  83 PASImsgrrkanPQDKVHPNK--AEFIRAKYQMLAFVHRLPCREDDSVTAKDlSKQLHSSVRTGN 145
Cdd:COG5347    95 QLLL--------PIKAKYDSSvaKKYIRKKYELKKFIDDSSSPSDFSSFSAS-STRTVDSVDDRL 150

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 1720413633  11 CADCNGPDPSWASVNRGTFICDECCSVHRSLGRHISQVRHLK--HTAWPPTLLQMVETLYNNGANSIWEHSL-----LDP 83
Cdd:cd17901    16 CADCGSPKPDWASVNLCVVICKRCAGEHRGLGPSVSKVRSLKmdRKVWTEELIELFLLLGNGKANQFWAANVppseaLCP 95

                          90       100
                  ....*....|....*....|....*...
gi 1720413633  84 ASIMSGRRkanpqdkvhpnkaEFIRAKY 111
Cdd:cd17901    96 SSSSEERR-------------HFITAKY 110

ArfGap with Rho-Gap domain, ANK repeat and PH domain-containing protein 2; 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. ARAP2 localizes to the cell periphery and on focal adhesions composed of paxillin and vinculin, and functions downstream of RhoA to regulate focal adhesion dynamics. ARAP2 is a PI(3,4,5)P3-dependent Arf6 GAP that binds RhoA-GTP, but it lacks the predicted catalytic arginine in the RhoGAP domain and does not have RhoGAP activity. ARAP2 reduces Rac1oGTP levels by reducing Arf6oGTP levels through GAP activity. AGAP2 also binds to and regulates focal adhesion kinase (FAK). Thus, ARAP2 signals through Arf6 and Rac1 to control focal adhesion morphology.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1720413633  11 CADCNGPDPSWASVNRGTFICDECCSVHRSLGRHISQVRHLKHTA--WPPTLLQMVETLYNNGANSIWEHSLLDPASIMS 88
Cdd:cd08856    21 CADCKAPDPDWASINLCVVICKKCAGQHRSLGPKDSKVRSLKMDAsiWSNELIELFIVVGNKPANLFWAANLFSEEDLHM 100

                          90       100
                  ....*....|....*....|....
gi 1720413633  89 GrrkANPQdkvhpNKAEFIRAKYQ 112
Cdd:cd08856   101 D---SDVE-----QRTPFITQKYK 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 1720413633   3 KRLRSSDVCADCNGPDPSWASVNRGTFICDECCSVHRSLGRHISQVRHLKHTAWPPTLLQMVETLYNNGANSIWEHSLLD 82
Cdd:cd08849    10 QRMTGNDVCCDCGAPDPTWLSTNLGILTCIECSGIHRELGVHYSRMQSLTLDVLGTSELLLAKNIGNAGFNEIMEACLPA 89

                          90       100
                  ....*....|....*....|....*....
gi 1720413633  83 PASImsgrrKANPQDKVHPNKaEFIRAKY 111
Cdd:cd08849    90 EDVV-----KPNPGSDMNARK-DYITAKY 112

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 1720413633  11 CADCNGPDPSWASVNRGTFICDECCSVHRSLGRHISQVRHLKHTAWPPTLLQMVETLYNNGANSIWEHSLLDpasimSGR 90
Cdd:cd08859    13 CADCQSKGPRWASWNIGVFICIRCAGIHRNLGVHISRVKSVNLDQWTQEQIQCMQEMGNGKANRLYEAFLPE-----NFR 87

                          90       100
                  ....*....|....*....|..
gi 1720413633  91 RkanPQdkVHPNKAEFIRAKYQ 112
Cdd:cd08859    88 R---PQ--TDQAVEGFIRDKYE 104

Ankyrin repeat [Signal transduction mechanisms];

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1720413633 137 LHSSVRTGNLETCLRLLSLGAQANFFHPEkGSTPLHVASKAGQILQAELLAVYGADPGTQDSSGKTPVDYARQGGHHELA 216
Cdd:COG0666   157 LHLAAANGNLEIVKLLLEAGADVNARDND-GETPLHLAAENGHLEIVKLLLEAGADVNAKDNDGKTALDLAAENGNLEIV 235

                  ....*
gi 1720413633 217 ERLIE 221
Cdd:COG0666   236 KLLLE 240

Ankyrin repeat [Signal transduction mechanisms];

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1720413633 137 LHSSVRTGNLETCLRLLSLGAQANFFHPEkGSTPLHVASKAGQILQAELLAVYGADPGTQDSSGKTPVDYARQGGHHELA 216
Cdd:COG0666   124 LHLAAYNGNLEIVKLLLEAGADVNAQDND-GNTPLHLAAANGNLEIVKLLLEAGADVNARDNDGETPLHLAAENGHLEIV 202

                  ....*
gi 1720413633 217 ERLIE 221
Cdd:COG0666   203 KLLLE 207

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        50
                  ....*....|....*....|....*....|....*....|....*....|
gi 1720413633   3 KRLRS---SDVCADCNGPDPSWASVNRGTFICDECCSVHRSLGRHISQVR 49
Cdd:cd09028    11 KRLRSvptNKVCFDCGAKNPSWASITYGVFLCIDCSGIHRSLGVHLSFIR 60

ADAP1 GTPase activating protein for Arf, with dual PH domains; The ADAP subfamily, ArfGAPs with dual pleckstrin homology (PH) domains, includes two members: ADAP1 and ADAP2. Both ADAP1 (also known as centaurin-alpha1, p42(IP4), or PIP3BP) and ADAP2 (centaurin-alpha2) display a GTPase-activating protein (GAP) activity toward Arf6 (ADP-ribosylation factor 6), which is involved in protein trafficking that regulates endocytic recycling, cytoskeleton remodeling, and neuronal differentiation. ADAP2 has high sequence similarity to the ADAP1 and they both contain a ArfGAP domain at the N-terminus, followed by two PH domains. However, ADAP1, unlike ADAP2, contains a putative N-terminal nuclear localization signal. The PH domains of ADAP1bind to the two second messenger molecules phosphatidylinositol 3,4,5-trisphosphate (PI(3,4,5)P3) and inositol 1,3,4,5-tetrakisphosphate (I(1,3,4,5)P4) with identical high affinity, whereas those of ADAP2 specifically binds phosphatidylinositol 3,4-bisphosphate (PI(3,4)P2) and PI(3,4,5)P3, which are produced by activated phosphatidylinositol 3-kinase. ADAP1 is predominantly expressed in the brain neurons, while ADAP2 is broadly expressed, including the adipocytes, heart, and skeletal muscle but not in the brain. The limited distribution and high expression of ADAP1 in the brain indicates that ADAP1 is important for neuronal functions. ADAP1 has been shown to highly expressed in the neurons and plagues of Alzheimer's disease patients. In other hand, ADAP2 gene deletion has been shown to cause circulatory deficiencies and heart shape defects in zebrafish, indicating that ADAP2 has a vital role in heart development. Taken together, the hemizygous deletion of ADAP2 gene may be contributing to the cardiovascular malformation in patients with neurofibromatosis type 1 (NF1) microdeletions.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1720413633  10 VCADCNGPDPSWASVNRGTFICDECCSVHRSLGRhISQVRHLKHTAWPPTLLQMVETLYNNGANSIWEhslldpASIMSG 89
Cdd:cd08843    19 RCADCGAPDPDWASYTLGVFICLSCSGIHRNIPQ-VSKVKSVRLDAWEEAQVEFMASHGNDAARARFE------SKVPSF 91

                          90       100
                  ....*....|....*....|..
gi 1720413633  90 RRKANPQDkVHPNKAEFIRAKY 111
Cdd:cd08843    92 YYRPTPSD-CQLLREQWIRAKY 112

ADAP2 GTPase activating protein for Arf, with dual PH domains; The ADAP subfamily, ArfGAPs with dual pleckstrin homology (PH) domains, includes two members: ADAP1 and ADAP2. Both ADAP1 (also known as centaurin-alpha1, p42(IP4), or PIP3BP) and ADAP2 (centaurin-alpha2) display a GTPase-activating protein (GAP) activity toward Arf6 (ADP-ribosylation factor 6), which is involved in protein trafficking that regulates endocytic recycling, cytoskeleton remodeling, and neuronal differentiation. ADAP2 has high sequence similarity to the ADAP1 and they both contain a ArfGAP domain at the N-terminus, followed by two PH domains. However, ADAP1, unlike ADAP2, contains a putative N-terminal nuclear localization signal. The PH domains of ADAP1bind to the two second messenger molecules phosphatidylinositol 3,4,5-trisphosphate (PI(3,4,5)P3) and inositol 1,3,4,5-tetrakisphosphate (I(1,3,4,5)P4) with identical high affinity, whereas those of ADAP2 specifically binds phosphatidylinositol 3,4-bisphosphate (PI(3,4)P2) and PI(3,4,5)P3, which are produced by activated phosphatidylinositol 3-kinase. ADAP1 is predominantly expressed in the brain neurons, while ADAP2 is broadly expressed, including the adipocytes, heart, and skeletal muscle but not in the brain. The limited distribution and high expression of ADAP1 in the brain indicates that ADAP1 is important for neuronal functions. ADAP1 has been shown to highly expressed in the neurons and plagues of Alzheimer's disease patients. In other hand, ADAP2 gene deletion has been shown to cause circulatory deficiencies and heart shape defects in zebrafish, indicating that ADAP2 has a vital role in heart development. Taken together, the hemizygous deletion of ADAP2 gene may be contributing to the cardiovascular malformation in patients with neurofibromatosis type 1 (NF1) microdeletions.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1720413633   4 RLRSSDVCADCNGPDPSWASVNRGTFICDECCSVHRSLGRhISQVRHLKHTAWPPTLLQMVETLYNNGANSIWEHSLldP 83
Cdd:cd08844    13 KLPGNSVCADCGAPDPDWASYTLGIFICLNCSGVHRNLPD-ISRVKSIRLDFWEDELVEFMKENGNLKAKAKFEAFV--P 89

                          90       100
                  ....*....|....*....|....*...
gi 1720413633  84 ASIMsgRRKANPQDKVhpnKAEFIRAKY 111
Cdd:cd08844    90 PFYY--RPQANDCDVL---KEQWIRAKY 112

ArfGAP domain of the AGFG subfamily (ArfGAP domain and FG repeat-containing proteins); 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 AGFG is related to nucleoporins, which is a class of proteins that mediate nucleocytoplasmic transport. AGFG 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, 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 1720413633  11 CADCNGPDPSWASVNRGTFICDECCSVHRSLGRHisqVRHLKHTAWPPTLLQMVETLYNNGANSIWeHSLLDPASIMsgR 90
Cdd:cd08838    16 CFDCGQRGPTYVNLTFGTFVCTTCSGIHREFNHR---VKSISMSTFTPEEVEFLQAGGNEVARKIW-LAKWDPRTDP--E 89

                          90       100
                  ....*....|....*....|..
gi 1720413633  91 RKANPQDKVHpnkaEFIRAKYQ 112
Cdd:cd08838    90 PDSGDDQKIR----EFIRLKYV 107

Ankyrin repeats (3 copies);

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1720413633 137 LHSSVRTGNLETCLRLLSLGAQANFFHPEkGSTPLHVASKAGQILQAELLAVYGAdpGTQDSSGKTPVDYARQGGHHELA 216
Cdd:pfam12796   1 LHLAAKNGNLELVKLLLENGADANLQDKN-GRTALHLAAKNGHLEIVKLLLEHAD--VNLKDNGRTALHYAARSGHLEIV 77

                          90
                  ....*....|...
gi 1720413633 217 ERLIEIQYELTDR 229
Cdd:pfam12796  78 KLLLEKGADINVK 90

Helical motif in the GIT family of ADP-ribosylation factor GTPase-activating proteins; Helical motif in the GIT family of ADP-ribosylation factor GTPase-activating proteins, and in yeast Spa2p and Sph1p (CPP; unpublished results). In p95-APP1 the N-terminal GIT motif might be involved in binding PIX.

                           10        20        30
                   ....*....|....*....|....*....|.
gi 1720413633  268 AKKKLQSLSNHLFEELAMDVYDEVDRRETDA 298
Cdd:smart00555   1 ARQKLARLSDEQFQKLLTDLNDELKRRENEA 31