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Conserved domains on  [gi|25147080|ref|NP_509761|]
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Arf-GAP domain-containing protein [Caenorhabditis elegans]

Protein Classification

Graphical summary

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List of domain hits

 Name Accession Description Interval E-value
ArfGap smart00105
Putative GTP-ase activating proteins for the small GTPase, ARF; Putative zinc fingers with ...
 7-127 3.30e-45

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.


:

Pssm-ID: 214518 [Multi-domain]  Cd Length: 119  Bit Score: 156.73  E-value: 3.30e-45
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 25147080      7 LDLITSLE-QKECDDCGKKEVEWASVKKGTVICSECFCFHSYLGPSVSYLRHLRKSAWDEEHIRLVHALNTSNTNMIWES 85
Cdd:smart00105   1 LKLLRSIPgNKKCFDCGAPNPTWASVNLGVFLCIECSGIHRSLGVHISKVRSLTLDTWTEEELRLLQKGGNENANSIWES 80

                           90       100       110       120
                   ....*....|....*....|....*....|....*....|..
gi 25147080     86 ALYEGSTKFQKPMAQdpsHIKEQFVKEKYEKLTFQPKRGKDE 127
Cdd:smart00105  81 NLDDFSLKPPDDDDQ---QKYESFIAAKYEEKLFVPPESAEE 119
ANKYR COG0666
Ankyrin repeat [Signal transduction mechanisms];
122-212 4.58e-13

Ankyrin repeat [Signal transduction mechanisms];


:

Pssm-ID: 440430 [Multi-domain]  Cd Length: 289  Bit Score: 70.37  E-value: 4.58e-13
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 25147080 122 KRGKDEDLENSLNRQ-LIACARSDFAHVTLRLIALGADVNYPDPEtGDTALHVAAREGNSNQVELLFLYGADIMAPNREG 200
Cdd:COG0666 108 EAGADVNARDKDGETpLHLAAYNGNLEIVKLLLEAGADVNAQDND-GNTPLHLAAANGNLEIVKLLLEAGADVNARDNDG 186

                        90
                ....*....|..
gi 25147080 201 MLPYILARDAGH 212
Cdd:COG0666 187 ETPLHLAAENGH 198
GIT1_C super family cl20096
G protein-coupled receptor kinase-interacting protein 1 C term; This domain family is found in ...
 570-669 6.53e-07

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.


The actual alignment was detected with superfamily member pfam12205:

Pssm-ID: 463492  Cd Length: 110  Bit Score: 48.44  E-value: 6.53e-07
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 25147080   570 KTRVIQQSEKITRHIKTLLqhghngnldMNARGGAHD--------IACAINSLITILLPYVRHEK----IDTLTDAVVLL 637
Cdd:pfam12205   1 PDNVVRQTELITKAIQELL---------KAAQEGRHSefldcaerIRSAVTEMAALFPKSPRSETvreaLKALTDAADKL 71

                          90       100       110
                  ....*....|....*....|....*....|....*...
gi 25147080   638 NAKCNSPVLMPMD------IVDAAQTIAEKLRLIIMEF 669
Cdd:pfam12205  72 QAECVSLKASPGPddssqeIITAAYDIAKAAKELVTLF 109
GIT smart00555
Helical motif in the GIT family of ADP-ribosylation factor GTPase-activating proteins; Helical ...
 326-356 1.64e-06

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.


:

Pssm-ID: 128828  Cd Length: 31  Bit Score: 44.85  E-value: 1.64e-06
                           10        20        30
                   ....*....|....*....|....*....|.
gi 25147080    326 RRQKLAKFTPIQFTILLIDLIKDQKRRITGD 356
Cdd:smart00555   1 ARQKLARLSDEQFQKLLTDLNDELKRRENEA 31
GIT smart00555
Helical motif in the GIT family of ADP-ribosylation factor GTPase-activating proteins; Helical ...
 264-294 1.69e-06

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.


:

Pssm-ID: 128828  Cd Length: 31  Bit Score: 44.85  E-value: 1.69e-06
                           10        20        30
                   ....*....|....*....|....*....|.
gi 25147080    264 SRAAISVLPKGQFFDLCEDAFDETVRRENEV 294
Cdd:smart00555   1 ARQKLARLSDEQFQKLLTDLNDELKRRENEA 31
 
Name Accession Description Interval E-value
ArfGap smart00105
Putative GTP-ase activating proteins for the small GTPase, ARF; Putative zinc fingers with ...
 7-127 3.30e-45

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.


Pssm-ID: 214518 [Multi-domain]  Cd Length: 119  Bit Score: 156.73  E-value: 3.30e-45
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 25147080      7 LDLITSLE-QKECDDCGKKEVEWASVKKGTVICSECFCFHSYLGPSVSYLRHLRKSAWDEEHIRLVHALNTSNTNMIWES 85
Cdd:smart00105   1 LKLLRSIPgNKKCFDCGAPNPTWASVNLGVFLCIECSGIHRSLGVHISKVRSLTLDTWTEEELRLLQKGGNENANSIWES 80

                           90       100       110       120
                   ....*....|....*....|....*....|....*....|..
gi 25147080     86 ALYEGSTKFQKPMAQdpsHIKEQFVKEKYEKLTFQPKRGKDE 127
Cdd:smart00105  81 NLDDFSLKPPDDDDQ---QKYESFIAAKYEEKLFVPPESAEE 119
ArfGap_GIT cd08833
The GIT subfamily of ADP-ribosylation factor GTPase-activating proteins; The GIT (G-protein ...
 15-114 1.66e-42

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.


Pssm-ID: 350062 [Multi-domain]  Cd Length: 109  Bit Score: 148.99  E-value: 1.66e-42
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 25147080  15 QKECDDCGKKEVEWASVKKGTVICSECFCFHSYLGPSVSYLRHLRKSAWDEEHIRLVHALNTSNTNMIWESALYEGST-- 92
Cdd:cd08833   8 ARVCADCSAPDPEWASINRGVLICDECCSIHRSLGRHISQVKSLRKDQWPPSLLEMVQTLGNNGANSIWEHSLLDPSQsg 87

                        90       100
                ....*....|....*....|..
gi 25147080  93 KFQKPMAQDPSHIKEQFVKEKY 114
Cdd:cd08833  88 KRKPIPPDPVHPTKEEFIKAKY 109
ArfGap pfam01412
Putative GTPase activating protein for Arf; Putative zinc fingers with GTPase activating ...
 16-119 1.35e-19

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.


Pssm-ID: 460200 [Multi-domain]  Cd Length: 117  Bit Score: 84.58  E-value: 1.35e-19
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 25147080    16 KECDDCGKKEVEWASVKKGTVICSECFCFHSYLGPSVSYLRHLRKSAWDEEHIRLVHALNTSNTNMIWESALyegsTKFQ 95
Cdd:pfam01412  14 KVCADCGAPNPTWASVNLGIFICIDCSGVHRSLGVHISKVRSLTLDTWTDEQLELMKAGGNDRANEFWEANL----PPSY 89

                          90       100
                  ....*....|....*....|....
gi 25147080    96 KPMAQDPSHIKEQFVKEKYEKLTF 119
Cdd:pfam01412  90 KPPPSSDREKRESFIRAKYVEKKF 113
ANKYR COG0666
Ankyrin repeat [Signal transduction mechanisms];
122-212 4.58e-13

Ankyrin repeat [Signal transduction mechanisms];


Pssm-ID: 440430 [Multi-domain]  Cd Length: 289  Bit Score: 70.37  E-value: 4.58e-13
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 25147080 122 KRGKDEDLENSLNRQ-LIACARSDFAHVTLRLIALGADVNYPDPEtGDTALHVAAREGNSNQVELLFLYGADIMAPNREG 200
Cdd:COG0666 108 EAGADVNARDKDGETpLHLAAYNGNLEIVKLLLEAGADVNAQDND-GNTPLHLAAANGNLEIVKLLLEAGADVNARDNDG 186

                        90
                ....*....|..
gi 25147080 201 MLPYILARDAGH 212
Cdd:COG0666 187 ETPLHLAAENGH 198
COG5347 COG5347
GTPase-activating protein that regulates ARFs (ADP-ribosylation factors), involved in ...
 1-116 3.31e-12

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


Pssm-ID: 227651 [Multi-domain]  Cd Length: 319  Bit Score: 67.88  E-value: 3.31e-12
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 25147080   1 MYTAEALDLITSL-EQKECDDCGKKEVEWASVKKGTVICSECFCFHSYLGPSVSYLRHLRKSAWDEEHIRLVHALNTSNT 79
Cdd:COG5347   5 SEDRKLLKLLKSDsSNKKCADCGAPNPTWASVNLGVFLCIDCAGVHRSLGVHISKVKSLTLDNWTEEELRRMEVGGNSNA 84

                        90       100       110
                ....*....|....*....|....*....|....*..
gi 25147080  80 NMIWESALYEGSTKFQKpmAQDPSHIKEQFVKEKYEK 116
Cdd:COG5347  85 NRFYEKNLLDQLLLPIK--AKYDSSVAKKYIRKKYEL 119
GIT1_C pfam12205
G protein-coupled receptor kinase-interacting protein 1 C term; This domain family is found in ...
 570-669 6.53e-07

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.


Pssm-ID: 463492  Cd Length: 110  Bit Score: 48.44  E-value: 6.53e-07
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 25147080   570 KTRVIQQSEKITRHIKTLLqhghngnldMNARGGAHD--------IACAINSLITILLPYVRHEK----IDTLTDAVVLL 637
Cdd:pfam12205   1 PDNVVRQTELITKAIQELL---------KAAQEGRHSefldcaerIRSAVTEMAALFPKSPRSETvreaLKALTDAADKL 71

                          90       100       110
                  ....*....|....*....|....*....|....*...
gi 25147080   638 NAKCNSPVLMPMD------IVDAAQTIAEKLRLIIMEF 669
Cdd:pfam12205  72 QAECVSLKASPGPddssqeIITAAYDIAKAAKELVTLF 109
GIT smart00555
Helical motif in the GIT family of ADP-ribosylation factor GTPase-activating proteins; Helical ...
 326-356 1.64e-06

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.


Pssm-ID: 128828  Cd Length: 31  Bit Score: 44.85  E-value: 1.64e-06
                           10        20        30
                   ....*....|....*....|....*....|.
gi 25147080    326 RRQKLAKFTPIQFTILLIDLIKDQKRRITGD 356
Cdd:smart00555   1 ARQKLARLSDEQFQKLLTDLNDELKRRENEA 31
GIT smart00555
Helical motif in the GIT family of ADP-ribosylation factor GTPase-activating proteins; Helical ...
 264-294 1.69e-06

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.


Pssm-ID: 128828  Cd Length: 31  Bit Score: 44.85  E-value: 1.69e-06
                           10        20        30
                   ....*....|....*....|....*....|.
gi 25147080    264 SRAAISVLPKGQFFDLCEDAFDETVRRENEV 294
Cdd:smart00555   1 ARQKLARLSDEQFQKLLTDLNDELKRRENEA 31
Ank_5 pfam13857
Ankyrin repeats (many copies);
152-207 4.76e-06

Ankyrin repeats (many copies);


Pssm-ID: 433530 [Multi-domain]  Cd Length: 56  Bit Score: 44.26  E-value: 4.76e-06
                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....*..
gi 25147080   152 LIALG-ADVNYPDPEtGDTALHVAAREGNSNQVELLFLYGADIMAPNREGMLPYILA 207
Cdd:pfam13857   1 LLEHGpIDLNRLDGE-GYTPLHVAAKYGALEIVRVLLAYGVDLNLKDEEGLTALDLA 56
PLN03114 PLN03114
ADP-ribosylation factor GTPase-activating protein AGD10; Provisional
 14-71 1.26e-05

ADP-ribosylation factor GTPase-activating protein AGD10; Provisional


Pssm-ID: 178661 [Multi-domain]  Cd Length: 395  Bit Score: 47.93  E-value: 1.26e-05
                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|....*...
gi 25147080   14 EQKECDDCGKKEVEWASVKKGTVICSECFCFHSYLGPSVSYLRHLRKSAWDEEHIRLV 71
Cdd:PLN03114  21 DNKICFDCNAKNPTWASVTYGIFLCIDCSAVHRSLGVHISFVRSTNLDSWSSEQLKMM 78
PHA03095 PHA03095
ankyrin-like protein; Provisional
 125-206 7.21e-05

ankyrin-like protein; Provisional


Pssm-ID: 222980 [Multi-domain]  Cd Length: 471  Bit Score: 45.79  E-value: 7.21e-05
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 25147080  125 KDEDLENSLNRQLIACARSDFAHVTlRLIALGADVNYPDpETGDTALHVAAREGNSNQ---VELLFLYGADIMAPNREGM 201
Cdd:PHA03095   7 VDIIMEAALYDYLLNASNVTVEEVR-RLLAAGADVNFRG-EYGKTPLHLYLHYSSEKVkdiVRLLLEAGADVNAPERCGF 84


                 ....*
gi 25147080  202 LPYIL 206
Cdd:PHA03095  85 TPLHL 89
ANK smart00248
ankyrin repeats; Ankyrin repeats are about 33 amino acids long and occur in at least four ...
 167-193 4.68e-03

ankyrin repeats; Ankyrin repeats are about 33 amino acids long and occur in at least four consecutive copies. They are involved in protein-protein interactions. The core of the repeat seems to be an helix-loop-helix structure.


Pssm-ID: 197603 [Multi-domain]  Cd Length: 30  Bit Score: 34.87  E-value: 4.68e-03
                           10        20
                   ....*....|....*....|....*..
gi 25147080    167 GDTALHVAAREGNSNQVELLFLYGADI 193
Cdd:smart00248   2 GRTPLHLAAENGNLEVVKLLLDKGADI 28
GIT_SHD pfam08518
Spa2 homology domain (SHD) of GIT; GIT proteins are signaling integrators with ...
 327-354 6.58e-03

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.


Pssm-ID: 462506  Cd Length: 29  Bit Score: 34.68  E-value: 6.58e-03
                          10        20
                  ....*....|....*....|....*...
gi 25147080   327 RQKLAKFTPIQFTILLIDLIKDQKRRIT 354
Cdd:pfam08518   2 RQKLARLSNQQFEELVTDVYDELDRRQT 29
 
Name Accession Description Interval E-value
ArfGap smart00105
Putative GTP-ase activating proteins for the small GTPase, ARF; Putative zinc fingers with ...
 7-127 3.30e-45

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.


Pssm-ID: 214518 [Multi-domain]  Cd Length: 119  Bit Score: 156.73  E-value: 3.30e-45
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 25147080      7 LDLITSLE-QKECDDCGKKEVEWASVKKGTVICSECFCFHSYLGPSVSYLRHLRKSAWDEEHIRLVHALNTSNTNMIWES 85
Cdd:smart00105   1 LKLLRSIPgNKKCFDCGAPNPTWASVNLGVFLCIECSGIHRSLGVHISKVRSLTLDTWTEEELRLLQKGGNENANSIWES 80

                           90       100       110       120
                   ....*....|....*....|....*....|....*....|..
gi 25147080     86 ALYEGSTKFQKPMAQdpsHIKEQFVKEKYEKLTFQPKRGKDE 127
Cdd:smart00105  81 NLDDFSLKPPDDDDQ---QKYESFIAAKYEEKLFVPPESAEE 119
ArfGap_GIT cd08833
The GIT subfamily of ADP-ribosylation factor GTPase-activating proteins; The GIT (G-protein ...
 15-114 1.66e-42

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.


Pssm-ID: 350062 [Multi-domain]  Cd Length: 109  Bit Score: 148.99  E-value: 1.66e-42
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 25147080  15 QKECDDCGKKEVEWASVKKGTVICSECFCFHSYLGPSVSYLRHLRKSAWDEEHIRLVHALNTSNTNMIWESALYEGST-- 92
Cdd:cd08833   8 ARVCADCSAPDPEWASINRGVLICDECCSIHRSLGRHISQVKSLRKDQWPPSLLEMVQTLGNNGANSIWEHSLLDPSQsg 87

                        90       100
                ....*....|....*....|..
gi 25147080  93 KFQKPMAQDPSHIKEQFVKEKY 114
Cdd:cd08833  88 KRKPIPPDPVHPTKEEFIKAKY 109
ArfGap pfam01412
Putative GTPase activating protein for Arf; Putative zinc fingers with GTPase activating ...
 16-119 1.35e-19

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.


Pssm-ID: 460200 [Multi-domain]  Cd Length: 117  Bit Score: 84.58  E-value: 1.35e-19
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 25147080    16 KECDDCGKKEVEWASVKKGTVICSECFCFHSYLGPSVSYLRHLRKSAWDEEHIRLVHALNTSNTNMIWESALyegsTKFQ 95
Cdd:pfam01412  14 KVCADCGAPNPTWASVNLGIFICIDCSGVHRSLGVHISKVRSLTLDTWTDEQLELMKAGGNDRANEFWEANL----PPSY 89

                          90       100
                  ....*....|....*....|....
gi 25147080    96 KPMAQDPSHIKEQFVKEKYEKLTF 119
Cdd:pfam01412  90 KPPPSSDREKRESFIRAKYVEKKF 113
ArfGap_GIT2 cd08847
GIT2 GTPase activating protein for Arf; The GIT (G-protein coupled receptor kinase-interacting ...
 18-114 8.05e-19

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.


Pssm-ID: 350072 [Multi-domain]  Cd Length: 111  Bit Score: 82.38  E-value: 8.05e-19
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 25147080  18 CDDCGKKEVEWASVKKGTVICSECFCFHSYLGPSVSYLRHLRKSAWDEEHIRLVHALNTSNTNMIWESALYEGSTKF--- 94
Cdd:cd08847  11 CADCSTSDPRWASVNRGVLICDECCSVHRSLGRHISQVRHLKHTSWPPTLLQMVQTLYNNGANSIWEHSLLDPASIMsgk 90

                        90       100
                ....*....|....*....|.
gi 25147080  95 QKPMAQDPSHI-KEQFVKEKY 114
Cdd:cd08847  91 RKANPQDKVHPnKAEFIRAKY 111
ArfGap cd08204
GTPase-activating protein (GAP) for the ADP ribosylation factors (ARFs); ArfGAPs are a family ...
 16-114 7.78e-18

GTPase-activating protein (GAP) for the ADP ribosylation factors (ARFs); ArfGAPs are a family of proteins containing an ArfGAP catalytic domain that induces the hydrolysis of GTP bound to the small guanine nucleotide-binding protein Arf, a member of the Ras superfamily of GTPases. Like all GTP-binding proteins, Arf proteins function as molecular switches, cycling between GTP (active-membrane bound) and GDP (inactive-cytosolic) form. Conversion to the GTP-bound form requires a guanine nucleotide exchange factor (GEF), whereas conversion to the GDP-bound form is catalyzed by a GTPase activating protein (GAP). In that sense, ArfGAPs were originally proposed to function as terminators of Arf signaling, which is mediated by regulating Arf family GTP-binding proteins. However, recent studies suggest that ArfGAPs can also function as Arf effectors, independently of their GAP enzymatic activity to transduce signals in cells. The ArfGAP domain contains a C4-type zinc finger motif and a conserved arginine that is required for activity, within a specific spacing (CX2CX16CX2CX4R). ArfGAPs, which have multiple functional domains, regulate the membrane trafficking and actin cytoskeleton remodeling via specific interactions with signaling lipids such as phosphoinositides and trafficking proteins, which consequently affect cellular events such as cell growth, migration, and cancer invasion. The ArfGAP family, which includes 31 human ArfGAP-domain containing proteins, is divided into 10 subfamilies based on domain structure and sequence similarity. The ArfGAP nomenclature is mainly based on the protein domain structure. For example, ASAP1 contains ArfGAP, SH3, ANK repeat and PH domains; ARAPs contain ArfGAP, Rho GAP, ANK repeat and PH domains; ACAPs contain ArfGAP, BAR (coiled coil), ANK repeat and PH domains; and AGAPs contain Arf GAP, GTP-binding protein-like, ANK repeat and PH domains. Furthermore, the ArfGAPs can be classified into two major types of subfamilies, according to the overall domain structure: the ArfGAP1 type includes 6 subfamilies (ArfGAP1, ArfGAP2/3, ADAP, SMAP, AGFG, and GIT), which contain the ArfGAP domain at the N-terminus of the protein; and the AZAP type includes 4 subfamilies (ASAP, ACAP, AGAP, and ARAP), which contain an ArfGAP domain between the PH and ANK repeat domains.


Pssm-ID: 350058 [Multi-domain]  Cd Length: 106  Bit Score: 79.47  E-value: 7.78e-18
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 25147080  16 KECDDCGKKEVEWASVKKGTVICSECFCFHSYLGPSVSYLRHLRKSAWDEEHIRLVHALNTSNTNMIWESALyegSTKFQ 95
Cdd:cd08204  11 KVCADCGAPDPRWASINLGVFICIRCSGIHRSLGVHISKVRSLTLDSWTPEQVELMKAIGNARANAYYEANL---PPGFK 87

                        90
                ....*....|....*....
gi 25147080  96 KPMAQDPSHIKEQFVKEKY 114
Cdd:cd08204  88 KPTPDSSDEEREQFIRAKY 106
ArfGap_ADAP cd08832
ArfGap with dual PH domains; The ADAP subfamily, ArfGAPs with dual pleckstrin homology (PH) ...
 14-114 1.40e-17

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.


Pssm-ID: 350061 [Multi-domain]  Cd Length: 113  Bit Score: 78.84  E-value: 1.40e-17
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 25147080  14 EQKECDDCGKKEVEWASVKKGTVICSECFCFHSYLGPSVSYLRHLRKSAWDEEHIRLVHALNTSNTNMIWESALYEGstk 93
Cdd:cd08832  16 GNNTCADCGAPDPEWASYNLGVFICLDCSGIHRSLGTHISKVKSLRLDNWDDSQVEFMEENGNEKAKAKYEAHVPAF--- 92

                        90       100
                ....*....|....*....|.
gi 25147080  94 FQKPMAQDPSHIKEQFVKEKY 114
Cdd:cd08832  93 YRRPTPTDPQVLREQWIRAKY 113
ArfGap_GIT1 cd08846
GIT1 GTPase activating protein for Arf; The GIT (G-protein coupled receptor kinase-interacting ...
 18-114 3.53e-17

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.


Pssm-ID: 350071 [Multi-domain]  Cd Length: 111  Bit Score: 77.84  E-value: 3.53e-17
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 25147080  18 CDDCGKKEVEWASVKKGTVICSECFCFHSYLGPSVSYLRHLRKSAWDEEHIRLVHALNTSNTNMIWESALYEGS---TKF 94
Cdd:cd08846  11 CADCSAPDPGWASINRGVLICDECCSVHRSLGRHISIVKHLRHSAWPPTLLQMVHTLASNGANSIWEHSLLDPAqvqSGR 90

                        90       100
                ....*....|....*....|.
gi 25147080  95 QKPMAQDPSH-IKEQFVKEKY 114
Cdd:cd08846  91 RKANPQDKVHpTKSEFIRAKY 111
ArfGap_ACAP3 cd08850
ArfGAP domain of ACAP3 (ArfGAP with Coiled-coil, ANK repeat and PH domains 3); ACAP3 belongs ...
 17-119 1.36e-14

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.


Pssm-ID: 350075 [Multi-domain]  Cd Length: 116  Bit Score: 70.36  E-value: 1.36e-14
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 25147080  17 ECDDCGKKEVEWASVKKGTVICSECFCFHSYLGPSVSYLRHLRKSAWDEEHIRLVHALNTSNTNMIWESALYEGSTKfqK 96
Cdd:cd08850  15 QCCDCGQPDPRWASINLGILLCIECSGIHRSLGVHCSKVRSLTLDSWEPELLKLMCELGNSTVNQIYEAQCEELGLK--K 92

                        90       100
                ....*....|....*....|...
gi 25147080  97 PMAQDPSHIKEQFVKEKYEKLTF 119
Cdd:cd08850  93 PTASSSRQDKEAWIKAKYVEKKF 115
ArfGap_ACAP cd08835
ArfGAP domain of ACAP (ArfGAP with Coiled-coil, ANK repeat and PH domains) proteins; ArfGAP ...
 18-119 1.55e-14

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.


Pssm-ID: 350064 [Multi-domain]  Cd Length: 116  Bit Score: 70.37  E-value: 1.55e-14
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 25147080  18 CDDCGKKEVEWASVKKGTVICSECFCFHSYLGPSVSYLRHLRKSAWDEEHIRLVHALNTSNTNMIWESALYEGSTKfqKP 97
Cdd:cd08835  16 CCDCGSPDPRWASINLGVTLCIECSGIHRSLGVHVSKVRSLTLDSWEPELLKVMLELGNDVVNRIYEANVPDDGSV--KP 93

                        90       100
                ....*....|....*....|..
gi 25147080  98 MAQDPSHIKEQFVKEKYEKLTF 119
Cdd:cd08835  94 TPDSSRQEREAWIRAKYVEKKF 115
ArfGap_ACAP1 cd08852
ArfGAP domain of ACAP1 (ArfGAP with Coiled-coil, ANK repeat and PH domains 1); ACAP1 belongs ...
 5-122 2.26e-14

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.


Pssm-ID: 350077 [Multi-domain]  Cd Length: 120  Bit Score: 69.99  E-value: 2.26e-14
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 25147080   5 EALDLITSLE-QKECDDCGKKEVEWASVKKGTVICSECFCFHSYLGPSVSYLRHLRKSAWDEEHIRLVHALNTSNTNMIW 83
Cdd:cd08852   2 HAVAQVQSVDgNAQCCDCREPAPEWASINLGVTLCIQCSGIHRSLGVHFSKVRSLTLDSWEPELVKLMCELGNVIINQIY 81

                        90       100       110
                ....*....|....*....|....*....|....*....
gi 25147080  84 ESALYEGSTKfqKPMAQDPSHIKEQFVKEKYEKLTFQPK 122
Cdd:cd08852  82 EARIEAMAIK--KPGPSSSRQEKEAWIRAKYVEKKFITK 118
ArfGap_AGAP cd08836
ArfGAP with GTPase domain, ANK repeat and PH domains; The AGAP subfamily of ADP-ribosylation ...
 18-115 2.17e-13

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


Pssm-ID: 350065 [Multi-domain]  Cd Length: 108  Bit Score: 66.55  E-value: 2.17e-13
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 25147080  18 CDDCGKKEVEWASVKKGTVICSECFCFHSYLGPSVSYLRHLRKSAWDEEHIRLVHALNTSNTNMIWESALYEGstkfQKP 97
Cdd:cd08836  15 CVDCGAPNPDWASLNLGALMCIECSGIHRNLGTHISRVRSLDLDDWPVELLKVMSAIGNDLANSVWEGNTQGR----TKP 90

                        90
                ....*....|....*...
gi 25147080  98 MAQDPSHIKEQFVKEKYE 115
Cdd:cd08836  91 TPDSSREEKERWIRAKYE 108
ANKYR COG0666
Ankyrin repeat [Signal transduction mechanisms];
122-212 4.58e-13

Ankyrin repeat [Signal transduction mechanisms];


Pssm-ID: 440430 [Multi-domain]  Cd Length: 289  Bit Score: 70.37  E-value: 4.58e-13
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 25147080 122 KRGKDEDLENSLNRQ-LIACARSDFAHVTLRLIALGADVNYPDPEtGDTALHVAAREGNSNQVELLFLYGADIMAPNREG 200
Cdd:COG0666 108 EAGADVNARDKDGETpLHLAAYNGNLEIVKLLLEAGADVNAQDND-GNTPLHLAAANGNLEIVKLLLEAGADVNARDNDG 186

                        90
                ....*....|..
gi 25147080 201 MLPYILARDAGH 212
Cdd:COG0666 187 ETPLHLAAENGH 198
ArfGap_AGAP3 cd08855
ArfGAP with GTPase domain, ANK repeat and PH domain 3; The AGAP subfamily of ADP-ribosylation ...
 18-115 2.15e-12

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.


Pssm-ID: 350080 [Multi-domain]  Cd Length: 110  Bit Score: 63.92  E-value: 2.15e-12
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 25147080  18 CDDCGKKEVEWASVKKGTVICSECFCFHSYLGPSVSYLRHLRKSAWDEEHIRLVHALNTSNTNMIWESALyEGstkFQKP 97
Cdd:cd08855  17 CIDCDAPNPDWASLNLGALMCIECSGIHRNLGTHLSRVRSLDLDDWPVELSMVMTAIGNAMANSVWEGAL-DG---YSKP 92

                        90
                ....*....|....*...
gi 25147080  98 MAQDPSHIKEQFVKEKYE 115
Cdd:cd08855  93 GPDSTREEKERWIRAKYE 110
ArfGap_ACAP2 cd08851
ArfGAP domain of ACAP2 (ArfGAP with Coiled-coil, ANK repeat and PH domains 2); ACAP2 belongs ...
 18-119 2.80e-12

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.


Pssm-ID: 350076 [Multi-domain]  Cd Length: 116  Bit Score: 63.85  E-value: 2.80e-12
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 25147080  18 CDDCGKKEVEWASVKKGTVICSECFCFHSYLGPSVSYLRHLRKSAWDEEHIRLVHALNTSNTNMIWESALYEGSTKfqKP 97
Cdd:cd08851  16 CCDCGLADPRWASINLGITLCIECSGIHRSLGVHFSKVRSLTLDTWEPELLKLMCELGNDVINRIYEARVEKMGAK--KP 93

                        90       100
                ....*....|....*....|..
gi 25147080  98 MAQDPSHIKEQFVKEKYEKLTF 119
Cdd:cd08851  94 QPGGQRQEKEAYIRAKYVERKF 115
COG5347 COG5347
GTPase-activating protein that regulates ARFs (ADP-ribosylation factors), involved in ...
 1-116 3.31e-12

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


Pssm-ID: 227651 [Multi-domain]  Cd Length: 319  Bit Score: 67.88  E-value: 3.31e-12
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 25147080   1 MYTAEALDLITSL-EQKECDDCGKKEVEWASVKKGTVICSECFCFHSYLGPSVSYLRHLRKSAWDEEHIRLVHALNTSNT 79
Cdd:COG5347   5 SEDRKLLKLLKSDsSNKKCADCGAPNPTWASVNLGVFLCIDCAGVHRSLGVHISKVKSLTLDNWTEEELRRMEVGGNSNA 84

                        90       100       110
                ....*....|....*....|....*....|....*..
gi 25147080  80 NMIWESALYEGSTKFQKpmAQDPSHIKEQFVKEKYEK 116
Cdd:COG5347  85 NRFYEKNLLDQLLLPIK--AKYDSSVAKKYIRKKYEL 119
ANKYR COG0666
Ankyrin repeat [Signal transduction mechanisms];
137-215 6.68e-12

Ankyrin repeat [Signal transduction mechanisms];


Pssm-ID: 440430 [Multi-domain]  Cd Length: 289  Bit Score: 66.90  E-value: 6.68e-12
                        10        20        30        40        50        60        70
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 25147080 137 LIACARSDFAHVTLRLIALGADVNYPDPEtGDTALHVAAREGNSNQVELLFLYGADIMAPNREGMLPYILARDAGHGQL 215
Cdd:COG0666 157 LHLAAANGNLEIVKLLLEAGADVNARDND-GETPLHLAAENGHLEIVKLLLEAGADVNAKDNDGKTALDLAAENGNLEI 234
ArfGap_ARAP cd08837
ArfGap with Rho-Gap domain, ANK repeat and PH domain-containing proteins; The ARAP subfamily ...
 18-115 7.00e-12

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.


Pssm-ID: 350066 [Multi-domain]  Cd Length: 116  Bit Score: 62.78  E-value: 7.00e-12
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 25147080  18 CDDCGKKEVEWASVKKGTVICSECFCFHSYLGPSVSYLRHLR--KSAWDEEHIRLVHALNTSNTNMIWESALyegstkfQ 95
Cdd:cd08837  16 CADCGAPDPDWASINLCVVICKQCAGEHRSLGSNISKVRSLKmdTKVWTEELVELFLKLGNDRANRFWAANL-------P 88

                        90       100
                ....*....|....*....|...
gi 25147080  96 KPMAQDPSHIKEQ---FVKEKYE 115
Cdd:cd08837  89 PSEALHPDADSEQrreFITAKYR 111
ANKYR COG0666
Ankyrin repeat [Signal transduction mechanisms];
55-212 2.27e-11

Ankyrin repeat [Signal transduction mechanisms];


Pssm-ID: 440430 [Multi-domain]  Cd Length: 289  Bit Score: 64.98  E-value: 2.27e-11
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 25147080  55 LRHLRKSAWDEEHIRLVHALNTSNTNMIWESALYEGSTKFQKPMAQDPSHIKEQFVKEKYEKLTFQPKRGKDEDLENSLN 134
Cdd:COG0666   8 LLLLLAALLLLLLLALLLLAAALLLLLLLLLLLLLALLALALADALGALLLLAAALAGDLLVALLLLAAGADINAKDDGG 87

                        90       100       110       120       130       140       150
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 25147080 135 RQ-LIACARSDFAHVTLRLIALGADVNYPDPEtGDTALHVAAREGNSNQVELLFLYGADIMAPNREGMLPYILARDAGH 212
Cdd:COG0666  88 NTlLHAAARNGDLEIVKLLLEAGADVNARDKD-GETPLHLAAYNGNLEIVKLLLEAGADVNAQDNDGNTPLHLAAANGN 165
ArfGap_AGAP1 cd08854
ArfGAP with GTPase domain, ANK repeat and PH domain 1; The AGAP subfamily of ADP-ribosylation ...
 18-115 2.81e-11

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.


Pssm-ID: 350079 [Multi-domain]  Cd Length: 109  Bit Score: 60.79  E-value: 2.81e-11
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 25147080  18 CDDCGKKEVEWASVKKGTVICSECFCFHSYLGPSVSYLRHLRKSAWDEEHIRLVHALNTSNTNMIWESAlyegSTKFQKP 97
Cdd:cd08854  16 CVDCGAPNPTWASLNLGALICIECSGIHRNLGTHLSRVRSLDLDDWPRELTLVLTAIGNHMANSIWESC----TQGRTKP 91

                        90
                ....*....|....*...
gi 25147080  98 MAQDPSHIKEQFVKEKYE 115
Cdd:cd08854  92 APDSSREERESWIRAKYE 109
ArfGap_ARAP2 cd08856
ArfGap with Rho-Gap domain, ANK repeat and PH domain-containing protein 2; The ARAP subfamily ...
 16-120 1.43e-10

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.


Pssm-ID: 350081 [Multi-domain]  Cd Length: 121  Bit Score: 59.15  E-value: 1.43e-10
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 25147080  16 KECDDCGKKEVEWASVKKGTVICSECFCFHSYLGPSVSYLRHLR--KSAWDEEHIRLVHALNTSNTNMIWESALYEGStk 93
Cdd:cd08856  19 RSCADCKAPDPDWASINLCVVICKKCAGQHRSLGPKDSKVRSLKmdASIWSNELIELFIVVGNKPANLFWAANLFSEE-- 96

                        90       100
                ....*....|....*....|....*..
gi 25147080  94 fQKPMAQDPSHiKEQFVKEKYEKLTFQ 120
Cdd:cd08856  97 -DLHMDSDVEQ-RTPFITQKYKEGKFR 121
ArfGap_ARAP1 cd17901
ArfGap with Rho-Gap domain, ANK repeat and PH domain-containing protein 1; The ARAP subfamily ...
 18-83 2.02e-09

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.


Pssm-ID: 350088 [Multi-domain]  Cd Length: 116  Bit Score: 55.59  E-value: 2.02e-09
                        10        20        30        40        50        60
                ....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 25147080  18 CDDCGKKEVEWASVKKGTVICSECFCFHSYLGPSVSYLRHLR--KSAWDEEHIRLVHALNTSNTNMIW 83
Cdd:cd17901  16 CADCGSPKPDWASVNLCVVICKRCAGEHRGLGPSVSKVRSLKmdRKVWTEELIELFLLLGNGKANQFW 83
ArfGap_ADAP1 cd08843
ADAP1 GTPase activating protein for Arf, with dual PH domains; The ADAP subfamily, ArfGAPs ...
 18-114 3.53e-09

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.


Pssm-ID: 350069 [Multi-domain]  Cd Length: 112  Bit Score: 55.01  E-value: 3.53e-09
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 25147080  18 CDDCGKKEVEWASVKKGTVICSECFCFHSYLgPSVSYLRHLRKSAWDEEHIRLVHALNTSNTNMIWESALyegSTKFQKP 97
Cdd:cd08843  20 CADCGAPDPDWASYTLGVFICLSCSGIHRNI-PQVSKVKSVRLDAWEEAQVEFMASHGNDAARARFESKV---PSFYYRP 95

                        90
                ....*....|....*..
gi 25147080  98 MAQDPSHIKEQFVKEKY 114
Cdd:cd08843  96 TPSDCQLLREQWIRAKY 112
ArfGap_SMAP cd08839
Stromal membrane-associated proteins; a subfamily of the ArfGAP family; The SMAP subfamily of ...
 14-114 4.75e-09

Stromal membrane-associated proteins; 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.


Pssm-ID: 350068 [Multi-domain]  Cd Length: 103  Bit Score: 54.20  E-value: 4.75e-09
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 25147080  14 EQKECDDCGKKEVEWASVKKGTVICSECFCFHSYLGPSVSYLRHLRKSAWDEEHIRLVHALNTSNTNMIWESALYEGstk 93
Cdd:cd08839   9 DNKYCADCGAKGPRWASWNLGVFICIRCAGIHRNLGVHISKVKSVNLDSWTPEQVQSMQEMGNARANAYYEANLPDG--- 85

                        90       100
                ....*....|....*....|.
gi 25147080  94 FQKPmaQDPSHIkEQFVKEKY 114
Cdd:cd08839  86 FRRP--QTDSAL-ENFIRDKY 103
ArfGap_ASAP cd08834
ArfGAP domain of ASAP (Arf GAP, SH3, ANK repeat and PH domains) subfamily of ADP-ribosylation ...
 18-119 1.18e-08

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.


Pssm-ID: 350063 [Multi-domain]  Cd Length: 117  Bit Score: 53.38  E-value: 1.18e-08
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 25147080  18 CDDCGKKEVEWASVKKGTVICSECFCFHSYLGPSVSYLRHLRKSAWDEEHIRLVHALNTSNTNMIWESALYEGstkfQKP 97
Cdd:cd08834  18 CCDCGSPDPTWLSTNLGILTCIECSGVHRELGVHVSRIQSLTLDNLGTSELLLARNLGNEGFNEIMEANLPPG----YKP 93

                        90       100
                ....*....|....*....|..
gi 25147080  98 MAQDPSHIKEQFVKEKYEKLTF 119
Cdd:cd08834  94 TPNSDMEERKDFIRAKYVEKKF 115
ArfGap_ARAP3 cd17902
ArfGap with Rho-Gap domain, ANK repeat and PH domain-containing protein 3; The ARAP subfamily ...
 16-114 2.92e-08

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.


Pssm-ID: 350089 [Multi-domain]  Cd Length: 116  Bit Score: 52.22  E-value: 2.92e-08
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 25147080  16 KECDDCGKKEVEWASVKKGTVICSECFCFHSYLGPSVSYLRHLR--KSAWDEEHIRLVHALNTSNTNMIWESALYEGStk 93
Cdd:cd17902  14 RFCADCHASSPDWASINLCVVICKQCAGQHRSLGSGISKVQSLKldTSVWSNEIVQLFIVLGNDRANRFWAARLPASE-- 91

                        90       100
                ....*....|....*....|....
gi 25147080  94 fqkpmAQDPSHIKEQ---FVKEKY 114
Cdd:cd17902  92 -----ALHPDATPEQrreFISRKY 110
ArfGap_ADAP2 cd08844
ADAP2 GTPase activating protein for Arf, with dual PH domains; The ADAP subfamily, ArfGAPs ...
 7-114 8.61e-08

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.


Pssm-ID: 350070 [Multi-domain]  Cd Length: 112  Bit Score: 50.92  E-value: 8.61e-08
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 25147080   7 LDLITSLEQKECDDCGKKEVEWASVKKGTVICSECFCFHSYLgPSVSYLRHLRKSAWDEEHIRLVHALNTSNTNMIWESA 86
Cdd:cd08844   9 LELLKLPGNSVCADCGAPDPDWASYTLGIFICLNCSGVHRNL-PDISRVKSIRLDFWEDELVEFMKENGNLKAKAKFEAF 87

                        90       100
                ....*....|....*....|....*...
gi 25147080  87 LyegSTKFQKPMAQDPSHIKEQFVKEKY 114
Cdd:cd08844  88 V---PPFYYRPQANDCDVLKEQWIRAKY 112
ANKYR COG0666
Ankyrin repeat [Signal transduction mechanisms];
122-212 3.15e-07

Ankyrin repeat [Signal transduction mechanisms];


Pssm-ID: 440430 [Multi-domain]  Cd Length: 289  Bit Score: 52.65  E-value: 3.15e-07
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 25147080 122 KRGKDEDLENSLNRQ-LIACARSDFAHVTLRLIALGADVNYPDPEtGDTALHVAAREGNSNQVELLFLYGADIMAPNREG 200
Cdd:COG0666 174 EAGADVNARDNDGETpLHLAAENGHLEIVKLLLEAGADVNAKDND-GKTALDLAAENGNLEIVKLLLEAGADLNAKDKDG 252

                        90
                ....*....|..
gi 25147080 201 MLPYILARDAGH 212
Cdd:COG0666 253 LTALLLAAAAGA 264
GIT1_C pfam12205
G protein-coupled receptor kinase-interacting protein 1 C term; This domain family is found in ...
 570-669 6.53e-07

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.


Pssm-ID: 463492  Cd Length: 110  Bit Score: 48.44  E-value: 6.53e-07
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 25147080   570 KTRVIQQSEKITRHIKTLLqhghngnldMNARGGAHD--------IACAINSLITILLPYVRHEK----IDTLTDAVVLL 637
Cdd:pfam12205   1 PDNVVRQTELITKAIQELL---------KAAQEGRHSefldcaerIRSAVTEMAALFPKSPRSETvreaLKALTDAADKL 71

                          90       100       110
                  ....*....|....*....|....*....|....*...
gi 25147080   638 NAKCNSPVLMPMD------IVDAAQTIAEKLRLIIMEF 669
Cdd:pfam12205  72 QAECVSLKASPGPddssqeIITAAYDIAKAAKELVTLF 109
ArfGap_ArfGap1 cd08830
Arf1 GTPase-activating protein 1; ArfGAP (ADP Ribosylation Factor GTPase Activating Protein) ...
 18-73 1.21e-06

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.


Pssm-ID: 350059 [Multi-domain]  Cd Length: 115  Bit Score: 47.49  E-value: 1.21e-06
                        10        20        30        40        50
                ....*....|....*....|....*....|....*....|....*....|....*.
gi 25147080  18 CDDCGKKEVEWASVKKGTVICSECFCFHSYLGPSVSYLRHLRKSAWDEEHIRLVHA 73
Cdd:cd08830  17 CFDCGAPNPQWASVSYGIFICLECSGVHRGLGVHISFVRSITMDSWSEKQLKKMEL 72
GIT smart00555
Helical motif in the GIT family of ADP-ribosylation factor GTPase-activating proteins; Helical ...
 326-356 1.64e-06

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.


Pssm-ID: 128828  Cd Length: 31  Bit Score: 44.85  E-value: 1.64e-06
                           10        20        30
                   ....*....|....*....|....*....|.
gi 25147080    326 RRQKLAKFTPIQFTILLIDLIKDQKRRITGD 356
Cdd:smart00555   1 ARQKLARLSDEQFQKLLTDLNDELKRRENEA 31
GIT smart00555
Helical motif in the GIT family of ADP-ribosylation factor GTPase-activating proteins; Helical ...
 264-294 1.69e-06

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.


Pssm-ID: 128828  Cd Length: 31  Bit Score: 44.85  E-value: 1.69e-06
                           10        20        30
                   ....*....|....*....|....*....|.
gi 25147080    264 SRAAISVLPKGQFFDLCEDAFDETVRRENEV 294
Cdd:smart00555   1 ARQKLARLSDEQFQKLLTDLNDELKRRENEA 31
Ank_5 pfam13857
Ankyrin repeats (many copies);
152-207 4.76e-06

Ankyrin repeats (many copies);


Pssm-ID: 433530 [Multi-domain]  Cd Length: 56  Bit Score: 44.26  E-value: 4.76e-06
                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....*..
gi 25147080   152 LIALG-ADVNYPDPEtGDTALHVAAREGNSNQVELLFLYGADIMAPNREGMLPYILA 207
Cdd:pfam13857   1 LLEHGpIDLNRLDGE-GYTPLHVAAKYGALEIVRVLLAYGVDLNLKDEEGLTALDLA 56
ArfGap_ArfGap2 cd09029
Arf1 GTPase-activating protein 2; ArfGAP (ADP Ribosylation Factor GTPase Activating Protein) ...
 16-80 9.08e-06

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.


Pssm-ID: 350086 [Multi-domain]  Cd Length: 120  Bit Score: 45.44  E-value: 9.08e-06
                        10        20        30        40        50        60
                ....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 25147080  16 KECDDCGKKEVEWASVKKGTVICSECFCFHSYLGPSVSYLRHLR-KSAWDEEHIRLVHALNTSNTN 80
Cdd:cd09029  20 KACFDCGAKNPSWASITYGVFLCIDCSGVHRSLGVHLSFIRSTElDSNWNWFQLRCMQVGGNANAT 85
PLN03114 PLN03114
ADP-ribosylation factor GTPase-activating protein AGD10; Provisional
 14-71 1.26e-05

ADP-ribosylation factor GTPase-activating protein AGD10; Provisional


Pssm-ID: 178661 [Multi-domain]  Cd Length: 395  Bit Score: 47.93  E-value: 1.26e-05
                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|....*...
gi 25147080   14 EQKECDDCGKKEVEWASVKKGTVICSECFCFHSYLGPSVSYLRHLRKSAWDEEHIRLV 71
Cdd:PLN03114  21 DNKICFDCNAKNPTWASVTYGIFLCIDCSAVHRSLGVHISFVRSTNLDSWSSEQLKMM 78
ArfGap_ArfGap3 cd09028
Arf1 GTPase-activating protein 3; ArfGAP (ADP Ribosylation Factor GTPase Activating Protein) ...
 16-78 1.62e-05

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.


Pssm-ID: 350085 [Multi-domain]  Cd Length: 120  Bit Score: 44.67  E-value: 1.62e-05
                        10        20        30        40        50        60
                ....*....|....*....|....*....|....*....|....*....|....*....|....
gi 25147080  16 KECDDCGKKEVEWASVKKGTVICSECFCFHSYLGPSVSYLRHLR-KSAWDEEHIRLVHALNTSN 78
Cdd:cd09028  20 KVCFDCGAKNPSWASITYGVFLCIDCSGIHRSLGVHLSFIRSTElDSNWSWFQLRCMQVGGNAN 83
Ank_2 pfam12796
Ankyrin repeats (3 copies);
137-197 1.71e-05

Ankyrin repeats (3 copies);


Pssm-ID: 463710 [Multi-domain]  Cd Length: 91  Bit Score: 43.57  E-value: 1.71e-05
                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|.
gi 25147080   137 LIACARSDFAHVTLRLIALgADVNYPDpeTGDTALHVAAREGNSNQVELLFLYGADIMAPN 197
Cdd:pfam12796  34 LHLAAKNGHLEIVKLLLEH-ADVNLKD--NGRTALHYAARSGHLEIVKLLLEKGADINVKD 91
Ank_2 pfam12796
Ankyrin repeats (3 copies);
137-212 2.78e-05

Ankyrin repeats (3 copies);


Pssm-ID: 463710 [Multi-domain]  Cd Length: 91  Bit Score: 43.18  E-value: 2.78e-05
                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 25147080   137 LIACARSDFAHVTLRLIALGADVNYPDPEtGDTALHVAAREGNSNQVELLfLYGADIMAPNrEGMLPYILARDAGH 212
Cdd:pfam12796   1 LHLAAKNGNLELVKLLLENGADANLQDKN-GRTALHLAAKNGHLEIVKLL-LEHADVNLKD-NGRTALHYAARSGH 73
ArfGap_ASAP1 cd08848
ArfGAP domain of ASAP1 (ArfGAP with SH3 domain, ANK repeat and PH domain-containing protein 1); ...
 18-122 4.58e-05

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.


Pssm-ID: 350073 [Multi-domain]  Cd Length: 122  Bit Score: 43.49  E-value: 4.58e-05
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 25147080  18 CDDCGKKEVEWASVKKGTVICSECFCFHSYLGPSVSYLRHLRKSAWDEEHIRLVHALNTSNTNMIWESALYEGSTkfqKP 97
Cdd:cd08848  18 CCDCGSPDPTWLSTNLGILTCIECSGIHREMGVHISRIQSLELDKLGTSELLLAKNVGNNSFNDIMEGNLPSPSP---KP 94

                        90       100
                ....*....|....*....|....*
gi 25147080  98 MAQDPSHIKEQFVKEKYEKLTFQPK 122
Cdd:cd08848  95 SPSSDMTARKEYITAKYVEHRFSRK 119
PHA03095 PHA03095
ankyrin-like protein; Provisional
 125-206 7.21e-05

ankyrin-like protein; Provisional


Pssm-ID: 222980 [Multi-domain]  Cd Length: 471  Bit Score: 45.79  E-value: 7.21e-05
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 25147080  125 KDEDLENSLNRQLIACARSDFAHVTlRLIALGADVNYPDpETGDTALHVAAREGNSNQ---VELLFLYGADIMAPNREGM 201
Cdd:PHA03095   7 VDIIMEAALYDYLLNASNVTVEEVR-RLLAAGADVNFRG-EYGKTPLHLYLHYSSEKVkdiVRLLLEAGADVNAPERCGF 84


                 ....*
gi 25147080  202 LPYIL 206
Cdd:PHA03095  85 TPLHL 89
PHA02878 PHA02878
ankyrin repeat protein; Provisional
 146-198 1.24e-04

ankyrin repeat protein; Provisional


Pssm-ID: 222939 [Multi-domain]  Cd Length: 477  Bit Score: 44.87  E-value: 1.24e-04
                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|...
gi 25147080  146 AHVTLRLIALGADVNYPDPETGDTALHVAAREGNSNQVELLFLYGADIMAPNR 198
Cdd:PHA02878 147 AEITKLLLSYGADINMKDRHKGNTALHYATENKDQRLTELLLSYGANVNIPDK 199
ArfGap_AGFG2 cd17903
ArfGAP domain of AGFG2 (ArfGAP domain and FG repeat-containing protein 2); The ArfGAP domain ...
 11-116 2.55e-04

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


Pssm-ID: 350090 [Multi-domain]  Cd Length: 116  Bit Score: 41.13  E-value: 2.55e-04
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 25147080  11 TSLEQKECDDCGKKEVEWASVKKGTVICSECFCFHSYLGPSvSYLRHLRKSAWDEEHIRLVHALNTSNTNMIWeSALYEG 90
Cdd:cd17903  10 CSAANRHCFECAQRGVTYVDITVGSFVCTTCSGLLRGLNPP-HRVKSISMTTFTEPEVLFLQARGNEVCRKIW-LGLFDA 87

                        90       100
                ....*....|....*....|....*.
gi 25147080  91 STKFQkPMAQDPSHIKEqFVKEKYEK 116
Cdd:cd17903  88 RTSLI-PDSRDPQKVKE-FLQEKYEK 111
ArfGap_ArfGap2_3_like cd08831
Arf1 GTPase-activating protein 2/3-like; ArfGAP (ADP Ribosylation Factor GTPase Activating ...
 14-69 4.23e-04

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


Pssm-ID: 350060 [Multi-domain]  Cd Length: 116  Bit Score: 40.22  E-value: 4.23e-04
                        10        20        30        40        50
                ....*....|....*....|....*....|....*....|....*....|....*.
gi 25147080  14 EQKECDDCGKKEVEWASVKKGTVICSECFCFHSYLGPSVSYLRHLRKSAWDEEHIR 69
Cdd:cd08831  14 ENKVCFDCGAKNPTWASVTFGVFLCLDCSGVHRSLGVHISFVRSTNLDSWTPEQLR 69
ArfGap_ASAP3 cd17900
ArfGAP domain of ASAP3 (ArfGAP with ANK repeat and PH domain-containing protein 3); The ...
 16-126 4.89e-04

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.


Pssm-ID: 350087 [Multi-domain]  Cd Length: 124  Bit Score: 40.60  E-value: 4.89e-04
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 25147080  16 KECDDCGKKEVEWASVKKGTVICSECFCFHSYLGPSVSYLRHLRKSAWDEEHIRLvhALNTSNT--NMIWESALYEGSTK 93
Cdd:cd17900  16 SQCCDCGAPDPTWLSTNLGILTCIECSGIHRELGVRYSRIQSLTLDLLSTSELLL--AVSMGNTrfNEVMEATLPAHGGP 93

                        90       100       110
                ....*....|....*....|....*....|...
gi 25147080  94 fqKPMAQDPSHIKEQFVKEKYEKLTFQPKRGKD 126
Cdd:cd17900  94 --KPSAESDMGTRKDYIMAKYVEHRFVRKRCTP 124
ArfGap_ArfGap1_like cd08959
ARF1 GTPase-activating protein 1-like; ArfGAP (ADP Ribosylation Factor GTPase Activating ...
 14-70 5.10e-04

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.


Pssm-ID: 350084 [Multi-domain]  Cd Length: 115  Bit Score: 40.19  E-value: 5.10e-04
                        10        20        30        40        50
                ....*....|....*....|....*....|....*....|....*....|....*..
gi 25147080  14 EQKECDDCGKKEVEWASVKKGTVICSECFCFHSYLGPSVSYLRHLRKSAWDEEHIRL 70
Cdd:cd08959  13 ENKVCFDCGAKNPQWASVTYGIFICLDCSGVHRGLGVHISFVRSTTMDKWTEEQLRK 69
Ank_4 pfam13637
Ankyrin repeats (many copies);
139-186 7.82e-04

Ankyrin repeats (many copies);


Pssm-ID: 372654 [Multi-domain]  Cd Length: 54  Bit Score: 38.02  E-value: 7.82e-04
                          10        20        30        40
                  ....*....|....*....|....*....|....*....|....*...
gi 25147080   139 ACARSDFAhVTLRLIALGADVNYPDpETGDTALHVAAREGNSNQVELL 186
Cdd:pfam13637   8 AAASGHLE-LLRLLLEKGADINAVD-GNGETALHFAASNGNVEVLKLL 53
Ank pfam00023
Ankyrin repeat; Ankyrins are multifunctional adaptors that link specific proteins to the ...
 167-198 1.31e-03

Ankyrin repeat; Ankyrins are multifunctional adaptors that link specific proteins to the membrane-associated, spectrin- actin cytoskeleton. This repeat-domain is a 'membrane-binding' domain of up to 24 repeated units, and it mediates most of the protein's binding activities. Repeats 13-24 are especially active, with known sites of interaction for the Na/K ATPase, Cl/HCO(3) anion exchanger, voltage-gated sodium channel, clathrin heavy chain and L1 family cell adhesion molecules. The ANK repeats are found to form a contiguous spiral stack such that ion transporters like the anion exchanger associate in a large central cavity formed by the ANK repeat spiral, while clathrin and cell adhesion molecules associate with specific regions outside this cavity.


Pssm-ID: 459634 [Multi-domain]  Cd Length: 34  Bit Score: 36.50  E-value: 1.31e-03
                          10        20        30
                  ....*....|....*....|....*....|...
gi 25147080   167 GDTALHVAA-REGNSNQVELLFLYGADIMAPNR 198
Cdd:pfam00023   2 GNTPLHLAAgRRGNLEIVKLLLSKGADVNARDK 34
ArfGap_AGFG1 cd08857
ArfGAP domain of AGFG1 (ArfGAP domain and FG repeat-containing protein 1); The ArfGAP domain ...
 10-116 1.75e-03

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


Pssm-ID: 350082 [Multi-domain]  Cd Length: 116  Bit Score: 38.87  E-value: 1.75e-03
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 25147080  10 ITSL-EQKECDDCGKKEVEWASVKKGTVICSECFCFHSYLGPSvSYLRHLRKSAWDEEHIRLVHALNTSNTNMIWESALY 88
Cdd:cd08857   8 MTSLpHNRKCFDCDQRGPTYANMTVGSFVCTSCSGILRGLNPP-HRVKSISMTTFTQQEIEFLQKHGNEVCKQIWLGLFD 86

                        90       100
                ....*....|....*....|....*...
gi 25147080  89 EGSTKFqkPMAQDPSHIKEqFVKEKYEK 116
Cdd:cd08857  87 DRSSAI--PDFRDPQKVKE-FLQEKYEK 111
Ank_3 pfam13606
Ankyrin repeat; Ankyrins are multifunctional adaptors that link specific proteins to the ...
 167-193 3.29e-03

Ankyrin repeat; Ankyrins are multifunctional adaptors that link specific proteins to the membrane-associated, spectrin- actin cytoskeleton. This repeat-domain is a 'membrane-binding' domain of up to 24 repeated units, and it mediates most of the protein's binding activities.


Pssm-ID: 463933 [Multi-domain]  Cd Length: 30  Bit Score: 35.31  E-value: 3.29e-03
                          10        20
                  ....*....|....*....|....*..
gi 25147080   167 GDTALHVAAREGNSNQVELLFLYGADI 193
Cdd:pfam13606   2 GNTPLHLAARNGRLEIVKLLLENGADI 28
ArfGap_ASAP2 cd08849
ArfGAP domain of ASAP2 (ArfGAP2 with SH3 domain, ANK repeat and PH domain-containing protein 2) ...
 18-123 4.14e-03

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.


Pssm-ID: 350074 [Multi-domain]  Cd Length: 123  Bit Score: 37.65  E-value: 4.14e-03
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 25147080  18 CDDCGKKEVEWASVKKGTVICSECFCFHSYLGPSVSYLRHLRKSAWDEEHIRLVHALNTSNTNMIWESALyeGSTKFQKP 97
Cdd:cd08849  18 CCDCGAPDPTWLSTNLGILTCIECSGIHRELGVHYSRMQSLTLDVLGTSELLLAKNIGNAGFNEIMEACL--PAEDVVKP 95

                        90       100
                ....*....|....*....|....*.
gi 25147080  98 MAQDPSHIKEQFVKEKYEKLTFQPKR 123
Cdd:cd08849  96 NPGSDMNARKDYITAKYIERRYARKK 121
ANK smart00248
ankyrin repeats; Ankyrin repeats are about 33 amino acids long and occur in at least four ...
 167-193 4.68e-03

ankyrin repeats; Ankyrin repeats are about 33 amino acids long and occur in at least four consecutive copies. They are involved in protein-protein interactions. The core of the repeat seems to be an helix-loop-helix structure.


Pssm-ID: 197603 [Multi-domain]  Cd Length: 30  Bit Score: 34.87  E-value: 4.68e-03
                           10        20
                   ....*....|....*....|....*..
gi 25147080    167 GDTALHVAAREGNSNQVELLFLYGADI 193
Cdd:smart00248   2 GRTPLHLAAENGNLEVVKLLLDKGADI 28
GIT_SHD pfam08518
Spa2 homology domain (SHD) of GIT; GIT proteins are signaling integrators with ...
 327-354 6.58e-03

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.


Pssm-ID: 462506  Cd Length: 29  Bit Score: 34.68  E-value: 6.58e-03
                          10        20
                  ....*....|....*....|....*...
gi 25147080   327 RQKLAKFTPIQFTILLIDLIKDQKRRIT 354
Cdd:pfam08518   2 RQKLARLSNQQFEELVTDVYDELDRRQT 29
PHA02741 PHA02741
hypothetical protein; Provisional
 152-209 6.77e-03

hypothetical protein; Provisional


Pssm-ID: 165108 [Multi-domain]  Cd Length: 169  Bit Score: 38.10  E-value: 6.77e-03
                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|....*....
gi 25147080  152 LIALGADVNYPDPETGDTALHVAAREGNSNQVELLFLY-GADIMAPNREGMLPYILARD 209
Cdd:PHA02741  83 LIELGADINAQEMLEGDTALHLAAHRRDHDLAEWLCCQpGIDLHFCNADNKSPFELAID 141
PTZ00322 PTZ00322
6-phosphofructo-2-kinase/fructose-2,6-biphosphatase; Provisional
 152-222 6.79e-03

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


Pssm-ID: 140343 [Multi-domain]  Cd Length: 664  Bit Score: 39.50  E-value: 6.79e-03
                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 25147080  152 LIALGADVNYPDPEtGDTALHVAAREGNSNQVELLFLYGADIMAPNREGMLPYILARDAGHGQ-----LSHRIYEF 222
Cdd:PTZ00322 101 LLTGGADPNCRDYD-GRTPLHIACANGHVQVVRVLLEFGADPTLLDKDGKTPLELAEENGFREvvqllSRHSQCHF 175
Ank_4 pfam13637
Ankyrin repeats (many copies);
167-216 7.93e-03

Ankyrin repeats (many copies);


Pssm-ID: 372654 [Multi-domain]  Cd Length: 54  Bit Score: 34.94  E-value: 7.93e-03
                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|
gi 25147080   167 GDTALHVAAREGNSNQVELLFLYGADIMAPNREGMLPYILArdAGHGQLS 216
Cdd:pfam13637   1 ELTALHAAAASGHLELLRLLLEKGADINAVDGNGETALHFA--ASNGNVE 48
 
Blast search parameters
Data Source: Precalculated data, version = cdd.v.3.21
Preset Options:Database: CDSEARCH/cdd   Low complexity filter: no  Composition Based Adjustment: yes   E-value threshold: 0.01

References:

  • Wang J et al. (2023), "The conserved domain database in 2023", Nucleic Acids Res.51(D)384-8.
  • Lu S et al. (2020), "The conserved domain database in 2020", Nucleic Acids Res.48(D)265-8.
  • Marchler-Bauer A et al. (2017), "CDD/SPARCLE: functional classification of proteins via subfamily domain architectures.", Nucleic Acids Res.45(D)200-3.
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