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 28573879  39 RGKSRlQTEVCGDCGAGDPSWASINRGILLCADCCSVHRSLGRHISIVKSLRQGNWEPSVLNFVNSLNAHGANSVWEHHL 118
Cdd:cd08833   2 RGKSS-NARVCADCSAPDPEWASINRGVLICDECCSIHRSLGRHISQVKSLRKDQWPPSLLEMVQTLGNNGANSIWEHSL 80

                        90       100       110
                ....*....|....*....|....*....|....*..
gi 28573879 119 LDGSTNstggkhvpRWRKPTPKDALHPTKSDFIKAKH 155
Cdd:cd08833  81 LDPSQS--------GKRKPIPPDPVHPTKEEFIKAKY 109

Ankyrin repeat [Signal transduction mechanisms];

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 28573879 187 LHASVRTSNLETsLRFLVQ-GADPNYYHEDKlSTPLHMAAKFGQASQIEMLLIYGADVNALDGNGMTPLELARANNHNTI 265
Cdd:COG0666 124 LHLAAYNGNLEI-VKLLLEaGADVNAQDNDG-NTPLHLAAANGNLEIVKLLLEAGADVNARDNDGETPLHLAAENGHLEI 201

                ....*..
gi 28573879 266 AERLLDA 272
Cdd:COG0666 202 VKLLLEA 208

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 28573879   374 GRQKLARFNRAEFTGLLTDVLVDAMRRQN 402
Cdd:pfam08518   1 ARQKLARLSNQQFEELVTDVYDELDRRQT 29

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 28573879  39 RGKSRlQTEVCGDCGAGDPSWASINRGILLCADCCSVHRSLGRHISIVKSLRQGNWEPSVLNFVNSLNAHGANSVWEHHL 118
Cdd:cd08833   2 RGKSS-NARVCADCSAPDPEWASINRGVLICDECCSIHRSLGRHISQVKSLRKDQWPPSLLEMVQTLGNNGANSIWEHSL 80

                        90       100       110
                ....*....|....*....|....*....|....*..
gi 28573879 119 LDGSTNstggkhvpRWRKPTPKDALHPTKSDFIKAKH 155
Cdd:cd08833  81 LDPSQS--------GKRKPIPPDPVHPTKEEFIKAKY 109

Putative GTP-ase activating proteins for the small GTPase, 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 28573879     47 EVCGDCGAGDPSWASINRGILLCADCCSVHRSLGRHISIVKSLRQGNWEPSVLNFVNSLNAHGANSVWEHHLLDGStnst 126
Cdd:smart00105  11 KKCFDCGAPNPTWASVNLGVFLCIECSGIHRSLGVHISKVRSLTLDTWTEEELRLLQKGGNENANSIWESNLDDFS---- 86

                           90       100       110
                   ....*....|....*....|....*....|....*..
gi 28573879    127 ggkhvprwrKPTPKDALHPTKSDFIKAKHVNLTFVLK 163
Cdd:smart00105  87 ---------LKPPDDDDQQKYESFIAAKYEEKLFVPP 114

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 28573879  32 STRSKMPRGKSRLQTE----VCGDCGAGDPSWASINRGILLCADCCSVHRSLGRHISIVKSLRQGNWEPSVLNFVNSLNA 107
Cdd:COG5347   2 STKSEDRKLLKLLKSDssnkKCADCGAPNPTWASVNLGVFLCIDCAGVHRSLGVHISKVKSLTLDNWTEEELRRMEVGGN 81

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 28573879 108 HGANSVWEHHLLDGSTNSTGGKHvprwrkptpkDAlhPTKSDFIKAKhvnltFVLKPSlqDDDDGNGSAGCLEQELSRQL 187
Cdd:COG5347  82 SNANRFYEKNLLDQLLLPIKAKY----------DS--SVAKKYIRKK-----YELKKF--IDDSSSPSDFSSFSASSTRT 142

                       170       180       190       200
                ....*....|....*....|....*....|....*....|..
gi 28573879 188 HASVRTSN-LETSLRF------LVQGADPNYYHEDKLSTPLH 222
Cdd:COG5347 143 VDSVDDRLdSESQSRSssaslgNSNRPDDELNVESFQSTGSK 184

ADP-ribosylation factor GTPase-activating protein AGD10; Provisional

                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|..
gi 28573879   41 KSRLQTEVCGDCGAGDPSWASINRGILLCADCCSVHRSLGRHISIVKSLRQGNWEPSVLNFV 102
Cdd:PLN03114  17 KAKSDNKICFDCNAKNPTWASVTYGIFLCIDCSAVHRSLGVHISFVRSTNLDSWSSEQLKMM 78

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 28573879   314 ARGKLQLVPNKMFEELVMDLYDEVDRREC 342
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 28573879   374 GRQKLARFNRAEFTGLLTDVLVDAMRRQN 402
Cdd:pfam08518   1 ARQKLARLSNQQFEELVTDVYDELDRRQT 29

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 28573879    374 GRQKLARFNRAEFTGLLTDVLVDAMRRQNMA 404
Cdd:smart00555   1 ARQKLARLSDEQFQKLLTDLNDELKRRENEA 31

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 28573879  39 RGKSRlQTEVCGDCGAGDPSWASINRGILLCADCCSVHRSLGRHISIVKSLRQGNWEPSVLNFVNSLNAHGANSVWEHHL 118
Cdd:cd08833   2 RGKSS-NARVCADCSAPDPEWASINRGVLICDECCSIHRSLGRHISQVKSLRKDQWPPSLLEMVQTLGNNGANSIWEHSL 80

                        90       100       110
                ....*....|....*....|....*....|....*..
gi 28573879 119 LDGSTNstggkhvpRWRKPTPKDALHPTKSDFIKAKH 155
Cdd:cd08833  81 LDPSQS--------GKRKPIPPDPVHPTKEEFIKAKY 109

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 28573879  36 KMPRGksrlqtEVCGDCGAGDPSWASINRGILLCADCCSVHRSLGRHISIVKSLRQGNWEPSVLNFVNSLNAHGANSVWE 115
Cdd:cd08846   4 KGPRA------EVCADCSAPDPGWASINRGVLICDECCSVHRSLGRHISIVKHLRHSAWPPTLLQMVHTLASNGANSIWE 77

                        90       100       110       120
                ....*....|....*....|....*....|....*....|
gi 28573879 116 HHLLDGSTNSTGGkhvprwRKPTPKDALHPTKSDFIKAKH 155
Cdd:cd08846  78 HSLLDPAQVQSGR------RKANPQDKVHPTKSEFIRAKY 111

Putative GTP-ase activating proteins for the small GTPase, 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 28573879     47 EVCGDCGAGDPSWASINRGILLCADCCSVHRSLGRHISIVKSLRQGNWEPSVLNFVNSLNAHGANSVWEHHLLDGStnst 126
Cdd:smart00105  11 KKCFDCGAPNPTWASVNLGVFLCIECSGIHRSLGVHISKVRSLTLDTWTEEELRLLQKGGNENANSIWESNLDDFS---- 86

                           90       100       110
                   ....*....|....*....|....*....|....*..
gi 28573879    127 ggkhvprwrKPTPKDALHPTKSDFIKAKHVNLTFVLK 163
Cdd:smart00105  87 ---------LKPPDDDDQQKYESFIAAKYEEKLFVPP 114

ArfGap 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 28573879  48 VCGDCGAGDPSWASINRGILLCADCCSVHRSLGRHISIVKSLRQGNWEPSVLNFVNSLNAHGANSVWEhhlldgstnstg 127
Cdd:cd08832  19 TCADCGAPDPEWASYNLGVFICLDCSGIHRSLGTHISKVKSLRLDNWDDSQVEFMEENGNEKAKAKYE------------ 86

                        90       100
                ....*....|....*....|....*...
gi 28573879 128 gKHVPR-WRKPTPKDAlHPTKSDFIKAK 154
Cdd:cd08832  87 -AHVPAfYRRPTPTDP-QVLREQWIRAK 112

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 28573879  47 EVCGDCGAGDPSWASINRGILLCADCCSVHRSLGRHISIVKSLRQGNWEPSVLNFVNSLNAHGANSVWEHHLLDGStnst 126
Cdd:cd08834  16 DVCCDCGSPDPTWLSTNLGILTCIECSGVHRELGVHVSRIQSLTLDNLGTSELLLARNLGNEGFNEIMEANLPPGY---- 91

                        90       100       110
                ....*....|....*....|....*....|....*
gi 28573879 127 ggkhvprwrKPTPKDALhPTKSDFIKAKHVNLTFV 161
Cdd:cd08834  92 ---------KPTPNSDM-EERKDFIRAKYVEKKFV 116

ArfGAP domain of ACAP3 (ArfGAP with Coiled-coil, ANK repeat and PH domains 3); ACAP3 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. It has been shown that ACAP3 positively regulates neurite outgrowth through its GAP activity specific to Arf6 in mouse hippocampal neurons. ACAP1 (centaurin beta1) and ACAP2 centaurin beta2) also 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.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 28573879  47 EVCGDCGAGDPSWASINRGILLCADCCSVHRSLGRHISIVKSLRQGNWEPSVLNFVNSLNAHGANSVWEHHLLDGSTnst 126
Cdd:cd08850  14 DQCCDCGQPDPRWASINLGILLCIECSGIHRSLGVHCSKVRSLTLDSWEPELLKLMCELGNSTVNQIYEAQCEELGL--- 90

                        90       100       110
                ....*....|....*....|....*....|....*
gi 28573879 127 ggkhvprwRKPTPKDAlHPTKSDFIKAKHVNLTFV 161
Cdd:cd08850  91 --------KKPTASSS-RQDKEAWIKAKYVEKKFL 116

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 28573879  49 CGDCGAGDPSWASINRGILLCADCCSVHRSLGRHISIVKSLRQGNWEPSVLNFVNSLNAHGANSVWEhhlldGSTNSTGG 128
Cdd:cd08851  16 CCDCGLADPRWASINLGITLCIECSGIHRSLGVHFSKVRSLTLDTWEPELLKLMCELGNDVINRIYE-----ARVEKMGA 90

                        90       100       110
                ....*....|....*....|....*....|...
gi 28573879 129 KhvprwrKPTPKDAlHPTKSDFIKAKHVNLTFV 161
Cdd:cd08851  91 K------KPQPGGQ-RQEKEAYIRAKYVERKFV 116

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 28573879  48 VCGDCGAGDPSWASINRGILLCADCCSVHRSLGRHISIVKSLRQGNWEPSVLNFVNSLNAHGANSVWEhhlldgstNSTG 127
Cdd:cd08854  15 LCVDCGAPNPTWASLNLGALICIECSGIHRNLGTHLSRVRSLDLDDWPRELTLVLTAIGNHMANSIWE--------SCTQ 86

                        90       100
                ....*....|....*....|....*...
gi 28573879 128 GKhvprwRKPTPkDALHPTKSDFIKAKH 155
Cdd:cd08854  87 GR-----TKPAP-DSSREERESWIRAKY 108

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 28573879  32 STRSKMPRGKSRLQTE----VCGDCGAGDPSWASINRGILLCADCCSVHRSLGRHISIVKSLRQGNWEPSVLNFVNSLNA 107
Cdd:COG5347   2 STKSEDRKLLKLLKSDssnkKCADCGAPNPTWASVNLGVFLCIDCAGVHRSLGVHISKVKSLTLDNWTEEELRRMEVGGN 81

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 28573879 108 HGANSVWEHHLLDGSTNSTGGKHvprwrkptpkDAlhPTKSDFIKAKhvnltFVLKPSlqDDDDGNGSAGCLEQELSRQL 187
Cdd:COG5347  82 SNANRFYEKNLLDQLLLPIKAKY----------DS--SVAKKYIRKK-----YELKKF--IDDSSSPSDFSSFSASSTRT 142

                       170       180       190       200
                ....*....|....*....|....*....|....*....|..
gi 28573879 188 HASVRTSN-LETSLRF------LVQGADPNYYHEDKLSTPLH 222
Cdd:COG5347 143 VDSVDDRLdSESQSRSssaslgNSNRPDDELNVESFQSTGSK 184

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
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 28573879  39 RGKSRlqtevCGDCGAGDPSWASINRGILLCADCCSVHRSLGRHISIVKSLRQGNWEPSVLNFVNSLNAHGANSVWE 115
Cdd:cd08853  11 RGNSH-----CVDCETQNPKWASLNLGVLMCIECSGIHRNLGTHLSRVRSLDLDDWPVELRKVMSSIGNELANSIWE 82

ArfGap with Rho-Gap domain, ANK repeat and PH domain-containing proteins; 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.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 28573879  48 VCGDCGAGDPSWASINRGILLCADCCSVHRSLGRHISIVKSLRQGN--WEPSVLNFVNSLNAHGANSVWEHHLldgstns 125
Cdd:cd08837  15 FCADCGAPDPDWASINLCVVICKQCAGEHRSLGSNISKVRSLKMDTkvWTEELVELFLKLGNDRANRFWAANL------- 87

                        90       100       110
                ....*....|....*....|....*....|....*
gi 28573879 126 tggkhvprwrkpTPKDALHPTKS-----DFIKAKH 155
Cdd:cd08837  88 ------------PPSEALHPDADseqrrEFITAKY 110

ArfGAP domain of ASAP1 (ArfGAP with SH3 domain, ANK repeat and PH domain-containing protein 1); 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. 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 28573879  47 EVCGDCGAGDPSWASINRGILLCADCCSVHRSLGRHISIVKSLRQGNWEPSVLNFVNSLNAHGANSVWEHHLLDGSTnst 126
Cdd:cd08848  16 EVCCDCGSPDPTWLSTNLGILTCIECSGIHREMGVHISRIQSLELDKLGTSELLLAKNVGNNSFNDIMEGNLPSPSP--- 92

                        90       100       110
                ....*....|....*....|....*....|....*..
gi 28573879 127 ggkhvprwrKPTPKDALHPTKsDFIKAKHVNLTFVLK 163
Cdd:cd08848  93 ---------KPSPSSDMTARK-EYITAKYVEHRFSRK 119

Ankyrin repeat [Signal transduction mechanisms];

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 28573879 187 LHASVRTSNLETSLRFLVQGADPNYYHEDKlSTPLHMAAKFGQASQIEMLLIYGADVNALDGNGMTPLELARANNHNTIA 266
Cdd:COG0666  91 LHAAARNGDLEIVKLLLEAGADVNARDKDG-ETPLHLAAYNGNLEIVKLLLEAGADVNAQDNDGNTPLHLAAANGNLEIV 169

                ....*.
gi 28573879 267 ERLLDA 272
Cdd:COG0666 170 KLLLEA 175

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 28573879  41 KSRLQTEVCGDCGAGDPSWASINRGILLCADCCSVHRSLGRHISIVKSLRQGNWEPSVLNFVNSLNAHGANSVWEHHLLD 120
Cdd:cd17900  10 KSRPGNSQCCDCGAPDPTWLSTNLGILTCIECSGIHRELGVRYSRIQSLTLDLLSTSELLLAVSMGNTRFNEVMEATLPA 89

                        90       100       110       120
                ....*....|....*....|....*....|....*....|...
gi 28573879 121 GSTNstggkhvprwrKPTPKDALhPTKSDFIKAKHVNLTFVLK 163
Cdd:cd17900  90 HGGP-----------KPSAESDM-GTRKDYIMAKYVEHRFVRK 120

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        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 28573879  39 RGKSRLQTEVCGDCGAGDPSWASINRGILLCADCCSVHRSLGRHISIVKSLR-QGNWEPSVLNFVNSLNAHGANSVWEHH 117
Cdd:cd09028  12 RLRSVPTNKVCFDCGAKNPSWASITYGVFLCIDCSGIHRSLGVHLSFIRSTElDSNWSWFQLRCMQVGGNANASAFFHQH 91

                        90
                ....*....|....*.
gi 28573879 118 llDGSTNSTGGKHVPR 133
Cdd:cd09028  92 --GCTTNDTNAKYNSR 105

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 28573879  48 VCGDCGAGDPSWASINRGILLCADCCSVHRSLGRhISIVKSLRQGNWEPSVLNFVNSLNAHGANSVWEhhlldgstnstg 127
Cdd:cd08843  19 RCADCGAPDPDWASYTLGVFICLSCSGIHRNIPQ-VSKVKSVRLDAWEEAQVEFMASHGNDAARARFE------------ 85

                        90       100
                ....*....|....*....|....*...
gi 28573879 128 GKHVPRWRKPTPKDAlHPTKSDFIKAKH 155
Cdd:cd08843  86 SKVPSFYYRPTPSDC-QLLREQWIRAKY 112

ADP-ribosylation factor GTPase-activating protein AGD10; Provisional

                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|..
gi 28573879   41 KSRLQTEVCGDCGAGDPSWASINRGILLCADCCSVHRSLGRHISIVKSLRQGNWEPSVLNFV 102
Cdd:PLN03114  17 KAKSDNKICFDCNAKNPTWASVTYGIFLCIDCSAVHRSLGVHISFVRSTNLDSWSSEQLKMM 78

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
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 28573879  42 SRLQTEVCGDCGAGDPSWASINRGILLCADCCSVHRSLGRHISIVKSLRQGNWEPSVLNFVNSLNAHGANSVWEHHLLD 120
Cdd:cd08859   6 LEEENKFCADCQSKGPRWASWNIGVFICIRCAGIHRNLGVHISRVKSVNLDQWTQEQIQCMQEMGNGKANRLYEAFLPE 84

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 28573879  49 CGDCGAGDPSWASINRGILLCADCCSVHRSLGRHISIVKSLRQGN--WEPSVLNFVNSLNAHGANSVWEHHLldgstnst 126
Cdd:cd17902  16 CADCHASSPDWASINLCVVICKQCAGQHRSLGSGISKVQSLKLDTsvWSNEIVQLFIVLGNDRANRFWAARL-------- 87

                        90       100       110
                ....*....|....*....|....*....|....
gi 28573879 127 ggkhvprwrkpTPKDALHPTKS-----DFIKAKH 155
Cdd:cd17902  88 -----------PASEALHPDATpeqrrEFISRKY 110

Ankyrin repeat [Signal transduction mechanisms];

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 28573879 149 DFIKAKHVNLTFVLKPSLQDDDDGNGSAGCLEQELSRQLHASVRTSNLETSLRFLVQGADPNYYHEDKLSTPLHMAAKFG 228
Cdd:COG0666  19 LLLALLLLAAALLLLLLLLLLLLLALLALALADALGALLLLAAALAGDLLVALLLLAAGADINAKDDGGNTLLHAAARNG 98

                        90       100       110       120
                ....*....|....*....|....*....|....*....|....
gi 28573879 229 QASQIEMLLIYGADVNALDGNGMTPLELARANNHNTIAERLLDA 272
Cdd:COG0666  99 DLEIVKLLLEAGADVNARDKDGETPLHLAAYNGNLEIVKLLLEA 142

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 28573879   314 ARGKLQLVPNKMFEELVMDLYDEVDRREC 342
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 28573879   374 GRQKLARFNRAEFTGLLTDVLVDAMRRQN 402
Cdd:pfam08518   1 ARQKLARLSNQQFEELVTDVYDELDRRQT 29