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 1622842636   1 MSKRLRSSEVCADCSGPDPSWASVNRGTFICDECCSVHRSLGRHISQVRHLKHTPWPPTLLQMVETLYNNGANSIWEHSL 80
Cdd:cd08847     1 MSKRLRSSEVCADCSTSDPRWASVNRGVLICDECCSVHRSLGRHISQVRHLKHTSWPPTLLQMVQTLYNNGANSIWEHSL 80

                          90       100       110
                  ....*....|....*....|....*....|.
gi 1622842636  81 LDPASIMSGRRKANPQDKVHPNKAEFIRAKY 111
Cdd:cd08847    81 LDPASIMSGKRKANPQDKVHPNKAEFIRAKY 111

Ankyrin repeat [Signal transduction mechanisms];

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1622842636 123 RDDDSVTAkdlskqLHSSVRTGNLETCLRLLSLGAQANFFHPEkGNTPLHVASKAGQILQAELLAVYGADPGTQDSSGKT 202
Cdd:COG0666   149 QDNDGNTP------LHLAAANGNLEIVKLLLEAGADVNARDND-GETPLHLAAENGHLEIVKLLLEAGADVNAKDNDGKT 221

                          90       100       110       120       130       140
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 1622842636 203 PVDYARQGGHHELAERLVEIQYELTDRLAFYLCGRKPDHKNGQHFIIPQMADRRLSLDLSELAKAAK 269
Cdd:COG0666   222 ALDLAAENGNLEIVKLLLEAGADLNAKDKDGLTALLLAAAAGAALIVKLLLLALLLLAAALLDLLTL 288

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 1622842636 332 GRQKLARFNAHEFATLVIDILSDAKRRQQ 360
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 1622842636   1 MSKRLRSSEVCADCSGPDPSWASVNRGTFICDECCSVHRSLGRHISQVRHLKHTPWPPTLLQMVETLYNNGANSIWEHSL 80
Cdd:cd08847     1 MSKRLRSSEVCADCSTSDPRWASVNRGVLICDECCSVHRSLGRHISQVRHLKHTSWPPTLLQMVQTLYNNGANSIWEHSL 80

                          90       100       110
                  ....*....|....*....|....*....|.
gi 1622842636  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 1622842636 593 EDVIRKTEQITKNIQELLRAAQENKHDSYIPCSERIHVAVTEMAALFPKKPKSDMVRTSLRLLTSSAYRLQSECKKTLPg 672
Cdd:pfam12205   2 DNVVRQTELITKAIQELLKAAQEGRHSEFLDCAERIRSAVTEMAALFPKSPRSETVREALKALTDAADKLQAECVSLKA- 80

                          90       100       110
                  ....*....|....*....|....*....|....
gi 1622842636 673 DPGSPtdvqLVTQQVIQCAYDIAKAAKQLVTITT 706
Cdd:pfam12205  81 SPGPD----DSSQEIITAAYDIAKAAKELVTLFE 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 1622842636   3 KRLRSSEVCADCSGPDPSWASVNRGTFICDECCSVHRSLGRHISQVRHLKHTPWPPTLLQMVETLYNNGANSIWEHSLLD 82
Cdd:COG5347    15 KSDSSNKKCADCGAPNPTWASVNLGVFLCIDCAGVHRSLGVHISKVKSLTLDNWTEEELRRMEVGGNSNANRFYEKNLLD 94

                          90       100       110
                  ....*....|....*....|....*....|....*..
gi 1622842636  83 PASImsgrrkanPQDKVHPNK--AEFIRAKYQMLAFV 117
Cdd:COG5347    95 QLLL--------PIKAKYDSSvaKKYIRKKYELKKFI 123

ADP-ribosylation factor GTPase-activating protein AGD10; Provisional

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|...
gi 1622842636   3 KRLRS---SEVCADCSGPDPSWASVNRGTFICDECCSVHRSLGRHISQVRHLKHTPWPPTLLQMVETLYNNGA 72
Cdd:PLN03114   14 KKLKAksdNKICFDCNAKNPTWASVTYGIFLCIDCSAVHRSLGVHISFVRSTNLDSWSSEQLKMMIYGGNNRA 86

Ankyrin repeats (3 copies);

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1622842636 137 LHSSVRTGNLETCLRLLSLGAQANFFHPEkGNTPLHVASKAGQILQAELLAVYGAdpGTQDSSGKTPVDYARQGGHHELA 216
Cdd:pfam12796   1 LHLAAKNGNLELVKLLLENGADANLQDKN-GRTALHLAAKNGHLEIVKLLLEHAD--VNLKDNGRTALHYAARSGHLEIV 77

                          90
                  ....*....|...
gi 1622842636 217 ERLVEIQYELTDR 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 1622842636  268 AKKKLQSLSNHLFEELAMDVYDEVDRRETDA 298
Cdd:smart00555   1 ARQKLARLSDEQFQKLLTDLNDELKRRENEA 31

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 1622842636  332 GRQKLARFNAHEFATLVIDILSDAKRRQQGS 362
Cdd:smart00555   1 ARQKLARLSDEQFQKLLTDLNDELKRRENEA 31

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 1622842636   1 MSKRLRSSEVCADCSGPDPSWASVNRGTFICDECCSVHRSLGRHISQVRHLKHTPWPPTLLQMVETLYNNGANSIWEHSL 80
Cdd:cd08847     1 MSKRLRSSEVCADCSTSDPRWASVNRGVLICDECCSVHRSLGRHISQVRHLKHTSWPPTLLQMVQTLYNNGANSIWEHSL 80

                          90       100       110
                  ....*....|....*....|....*....|.
gi 1622842636  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 1622842636   1 MSKRLRSSEVCADCSGPDPSWASVNRGTFICDECCSVHRSLGRHISQVRHLKHTPWPPTLLQMVETLYNNGANSIWEHSL 80
Cdd:cd08846     1 MSRKGPRAEVCADCSAPDPGWASINRGVLICDECCSVHRSLGRHISIVKHLRHSAWPPTLLQMVHTLASNGANSIWEHSL 80

                          90       100       110
                  ....*....|....*....|....*....|.
gi 1622842636  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 1622842636 593 EDVIRKTEQITKNIQELLRAAQENKHDSYIPCSERIHVAVTEMAALFPKKPKSDMVRTSLRLLTSSAYRLQSECKKTLPg 672
Cdd:pfam12205   2 DNVVRQTELITKAIQELLKAAQEGRHSEFLDCAERIRSAVTEMAALFPKSPRSETVREALKALTDAADKLQAECVSLKA- 80

                          90       100       110
                  ....*....|....*....|....*....|....
gi 1622842636 673 DPGSPtdvqLVTQQVIQCAYDIAKAAKQLVTITT 706
Cdd:pfam12205  81 SPGPD----DSSQEIITAAYDIAKAAKELVTLFE 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 1622842636   1 MSKRLRSSE---VCADCSGPDPSWASVNRGTFICDECCSVHRSLGRHISQVRHLKHTPWPPTLLQMVETLYNNGANSIWE 77
Cdd:pfam01412   3 VLRELLKLPgnkVCADCGAPNPTWASVNLGIFICIDCSGVHRSLGVHISKVRSLTLDTWTDEQLELMKAGGNDRANEFWE 82

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|..
gi 1622842636  78 HSLLDPASImsgrrkanPQDKVHPNKAEFIRAKYQMLAFVHR 119
Cdd:pfam01412  83 ANLPPSYKP--------PPSSDREKRESFIRAKYVEKKFAKP 116

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 1622842636  10 VCADCSGPDPSWASVNRGTFICDECCSVHRSLGRHISQVRHLKHTPWPPTLLQMVETLYNNGANSIWEHSLldPAsimsG 89
Cdd:cd08832    19 TCADCGAPDPEWASYNLGVFICLDCSGIHRSLGTHISKVKSLRLDNWDDSQVEFMEENGNEKAKAKYEAHV--PA----F 92

                          90       100
                  ....*....|....*....|..
gi 1622842636  90 RRKANPQDkVHPNKAEFIRAKY 111
Cdd:cd08832    93 YRRPTPTD-PQVLREQWIRAKY 113

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 1622842636   9 EVCADCSGPDPSWASVNRGTFICDECCSVHRSLGRHISQVRHLKHTPWPPTLLQMVETLYNNGANSIWEHSLLDpasimS 88
Cdd:cd08835    14 AQCCDCGSPDPRWASINLGVTLCIECSGIHRSLGVHVSKVRSLTLDSWEPELLKVMLELGNDVVNRIYEANVPD-----D 88

                          90       100
                  ....*....|....*....|....*....
gi 1622842636  89 GRRKANPqDKVHPNKAEFIRAKYQMLAFV 117
Cdd:cd08835    89 GSVKPTP-DSSRQEREAWIRAKYVEKKFV 116

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 1622842636   1 MSKRLRSSEVCADCSGPDPSWASVNRGTFICDECCSVHRSLGRHISQVRHLKHTPWPPTLLQMVETLYNNGANSIWEHSL 80
Cdd:cd08834     8 EVKRLPGNDVCCDCGSPDPTWLSTNLGILTCIECSGVHRELGVHVSRIQSLTLDNLGTSELLLARNLGNEGFNEIMEANL 87

                          90       100       110
                  ....*....|....*....|....*....|....*.
gi 1622842636  81 -----LDPASIMSGRRkanpqdkvhpnkaEFIRAKY 111
Cdd:cd08834    88 ppgykPTPNSDMEERK-------------DFIRAKY 110

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 1622842636   3 KRLRSSEVCADCSGPDPSWASVNRGTFICDECCSVHRSLGRHISQVRHLKHTPWPPTLLQMVETLYNNGANSIWEHSlld 82
Cdd:cd08853     8 RNMRGNSHCVDCETQNPKWASLNLGVLMCIECSGIHRNLGTHLSRVRSLDLDDWPVELRKVMSSIGNELANSIWEGS--- 84

                          90       100       110
                  ....*....|....*....|....*....|
gi 1622842636  83 pasiMSGRRKANpQDKVHPNKAEFIRAKYQ 112
Cdd:cd08853    85 ----SQGQTKPS-SDSTREEKERWIRAKYE 109

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 1622842636   5 LRSSEVCADCSGPDPSWASVNRGTFICDECCSVHRSLGRHISQVRHLKHTPWPPTLLQMVETLYNNGANSIWEHSLLDpa 84
Cdd:cd08850    10 IAGNDQCCDCGQPDPRWASINLGILLCIECSGIHRSLGVHCSKVRSLTLDSWEPELLKLMCELGNSTVNQIYEAQCEE-- 87

                          90       100
                  ....*....|....*....|....*..
gi 1622842636  85 simSGRRKANPQDKvHPNKAEFIRAKY 111
Cdd:cd08850    88 ---LGLKKPTASSS-RQDKEAWIKAKY 110

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 1622842636  11 CADCSGPDPSWASVNRGTFICDECCSVHRSLGRHISQVRHLKHTPWPPTLLQMVETLYNNGANSIWEHSLLDpasimSGR 90
Cdd:cd08851    16 CCDCGLADPRWASINLGITLCIECSGIHRSLGVHFSKVRSLTLDTWEPELLKLMCELGNDVINRIYEARVEK-----MGA 90

                          90       100
                  ....*....|....*....|....*..
gi 1622842636  91 RKANPQDKVHPNKAeFIRAKYQMLAFV 117
Cdd:cd08851    91 KKPQPGGQRQEKEA-YIRAKYVERKFV 116

ARF1 GTPase-activating protein 1-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
                  ....*....|....*....|....*....|....*....|....*....|
gi 1622842636   3 KRLRSSE---VCADCSGPDPSWASVNRGTFICDECCSVHRSLGRHISQVR 49
Cdd:cd08959     6 KKLRSKPenkVCFDCGAKNPQWASVTYGIFICLDCSGVHRGLGVHISFVR 55

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 1622842636   7 SSEVCADCSGPDPSWASVNRGTFICDECCSVHRSLGRHISQVRHLK--HTPWPPTLLQMVETLYNNGANSIWEHSL---- 80
Cdd:cd17901    12 SNRFCADCGSPKPDWASVNLCVVICKRCAGEHRGLGPSVSKVRSLKmdRKVWTEELIELFLLLGNGKANQFWAANVppse 91

                          90       100       110
                  ....*....|....*....|....*....|..
gi 1622842636  81 -LDPASIMSGRRkanpqdkvhpnkaEFIRAKY 111
Cdd:cd17901    92 aLCPSSSSEERR-------------HFITAKY 110

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
                  ....*....|....*....|....*....|....*....|....*....|
gi 1622842636   3 KRLRSSE---VCADCSGPDPSWASVNRGTFICDECCSVHRSLGRHISQVR 49
Cdd:cd08830     6 RELQKLPgnnRCFDCGAPNPQWASVSYGIFICLECSGVHRGLGVHISFVR 55

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 1622842636   6 RSSEVCADCSGPDPSWASVNRGTFICDECCSVHRSLGRHISQVRHLK--HTPWPPTLLQMVETLYNNGANSIWEHSLldP 83
Cdd:cd17902    11 KANRFCADCHASSPDWASINLCVVICKQCAGQHRSLGSGISKVQSLKldTSVWSNEIVQLFIVLGNDRANRFWAARL--P 88

                          90       100       110
                  ....*....|....*....|....*....|....
gi 1622842636  84 ASimsgrrkanpqDKVHPN-----KAEFIRAKYQ 112
Cdd:cd17902    89 AS-----------EALHPDatpeqRREFISRKYR 111

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 1622842636   3 KRLRSSEVCADCSGPDPSWASVNRGTFICDECCSVHRSLGRHISQVRHLKHTPWPPTLLQMVETLYNNGANSIWEHSLLD 82
Cdd:cd08849    10 QRMTGNDVCCDCGAPDPTWLSTNLGILTCIECSGIHRELGVHYSRMQSLTLDVLGTSELLLAKNIGNAGFNEIMEACLPA 89

                          90       100
                  ....*....|....*....|....*....
gi 1622842636  83 PASImsgrrKANPQDKVHPNKaEFIRAKY 111
Cdd:cd08849    90 EDVV-----KPNPGSDMNARK-DYITAKY 112

Ankyrin repeat [Signal transduction mechanisms];

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1622842636 123 RDDDSVTAkdlskqLHSSVRTGNLETCLRLLSLGAQANFFHPEkGNTPLHVASKAGQILQAELLAVYGADPGTQDSSGKT 202
Cdd:COG0666   116 RDKDGETP------LHLAAYNGNLEIVKLLLEAGADVNAQDND-GNTPLHLAAANGNLEIVKLLLEAGADVNARDNDGET 188

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1622842636 203 PVDYARQGGHHELAERLVEiqyeltdrlafylCGRKPDHKNGQHFIIPQMADRRLSLDLSELAKAAKKKLQSLSNHLFEE 282
Cdd:COG0666   189 PLHLAAENGHLEIVKLLLE-------------AGADVNAKDNDGKTALDLAAENGNLEIVKLLLEAGADLNAKDKDGLTA 255

                  .
gi 1622842636 283 L 283
Cdd:COG0666   256 L 256

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 1622842636   3 KRLRS---SEVCADCSGPDPSWASVNRGTFICDECCSVHRSLGRHISQVR 49
Cdd:cd09028    11 KRLRSvptNKVCFDCGAKNPSWASITYGVFLCIDCSGIHRSLGVHLSFIR 60

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        40        50
                  ....*....|....*....|....*....|....*....|....*....|
gi 1622842636   3 KRLRS---SEVCADCSGPDPSWASVNRGTFICDECCSVHRSLGRHISQVR 49
Cdd:cd09029    11 KRLRAiptNKACFDCGAKNPSWASITYGVFLCIDCSGVHRSLGVHLSFIR 60

ADP-ribosylation factor GTPase-activating protein AGD10; Provisional

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|...
gi 1622842636   3 KRLRS---SEVCADCSGPDPSWASVNRGTFICDECCSVHRSLGRHISQVRHLKHTPWPPTLLQMVETLYNNGA 72
Cdd:PLN03114   14 KKLKAksdNKICFDCNAKNPTWASVTYGIFLCIDCSAVHRSLGVHISFVRSTNLDSWSSEQLKMMIYGGNNRA 86

Ankyrin repeat [Signal transduction mechanisms];

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1622842636  92 KANPQDKVHPNKAEFIRAKYQMLAFVHRLPCRDDDSVTAKDLSKQLHSSVRTGNLETCLRLLSLGAQANFFHPEKGNTPL 171
Cdd:COG0666    12 LAALLLLLLLALLLLAAALLLLLLLLLLLLLALLALALADALGALLLLAAALAGDLLVALLLLAAGADINAKDDGGNTLL 91

                          90       100       110       120       130
                  ....*....|....*....|....*....|....*....|....*....|
gi 1622842636 172 HVASKAGQILQAELLAVYGADPGTQDSSGKTPVDYARQGGHHELAERLVE 221
Cdd:COG0666    92 HAAARNGDLEIVKLLLEAGADVNARDKDGETPLHLAAYNGNLEIVKLLLE 141

Ankyrin repeats (3 copies);

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1622842636 137 LHSSVRTGNLETCLRLLSLGAQANFFHPEkGNTPLHVASKAGQILQAELLAVYGAdpGTQDSSGKTPVDYARQGGHHELA 216
Cdd:pfam12796   1 LHLAAKNGNLELVKLLLENGADANLQDKN-GRTALHLAAKNGHLEIVKLLLEHAD--VNLKDNGRTALHYAARSGHLEIV 77

                          90
                  ....*....|...
gi 1622842636 217 ERLVEIQYELTDR 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 1622842636  268 AKKKLQSLSNHLFEELAMDVYDEVDRRETDA 298
Cdd:smart00555   1 ARQKLARLSDEQFQKLLTDLNDELKRRENEA 31

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

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1622842636 118 HRLPCRDD-DSVTAKDLSKQLHSSVRTGNLETCLRLLSLGAQANF--FHpekGNTPLHVASKAGQILQAELLAVYGADPG 194
Cdd:PTZ00322   66 HNLTTEEViDPVVAHMLTVELCQLAASGDAVGARILLTGGADPNCrdYD---GRTPLHIACANGHVQVVRVLLEFGADPT 142

                          90       100
                  ....*....|....*....|....*
gi 1622842636 195 TQDSSGKTPVDYARQGGHHELAERL 219
Cdd:PTZ00322  143 LLDKDGKTPLELAEENGFREVVQLL 167