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Conserved domains on  [gi|564359681|ref|XP_006241562|]
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arf-GAP with GTPase, ANK repeat and PH domain-containing protein 2 isoform X3 [Rattus norvegicus]

Protein Classification

arf-GAP with GTPase, ANK repeat and PH domain-containing protein( domain architecture ID 12936410)

arf-GAP with GTPase, ANK repeat and PH domain-containing protein such as Caenorhabditis elegans CNT-2, which is a GTPase-activating protein for the ADP ribosylation factor family and involved in cell autonomous neuroblast asymmetric divisions that generate one precursor cell and one apoptotic cell probably by controlling endocytosis

Graphical summary

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List of domain hits

Name Accession Description Interval E-value
Centaurin_gamma cd04103
Centaurin gamma (CENTG) GTPase; The centaurins (alpha, beta, gamma, and delta) are large, ...
71-230 1.71e-96

Centaurin gamma (CENTG) GTPase; The centaurins (alpha, beta, gamma, and delta) are large, multi-domain proteins that all contain an ArfGAP domain and ankyrin repeats, and in some cases, numerous additional domains. Centaurin gamma contains an additional GTPase domain near its N-terminus. The specific function of this GTPase domain has not been well characterized, but centaurin gamma 2 (CENTG2) may play a role in the development of autism. Centaurin gamma 1 is also called PIKE (phosphatidyl inositol (PI) 3-kinase enhancer) and centaurin gamma 2 is also known as AGAP (ArfGAP protein with a GTPase-like domain, ankyrin repeats and a Pleckstrin homology domain) or GGAP. Three isoforms of PIKE have been identified. PIKE-S (short) and PIKE-L (long) are brain-specific isoforms, with PIKE-S restricted to the nucleus and PIKE-L found in multiple cellular compartments. A third isoform, PIKE-A was identified in human glioblastoma brain cancers and has been found in various tissues. GGAP has been shown to have high GTPase activity due to a direct intramolecular interaction between the N-terminal GTPase domain and the C-terminal ArfGAP domain. In human tissue, AGAP mRNA was detected in skeletal muscle, kidney, placenta, brain, heart, colon, and lung. Reduced expression levels were also observed in the spleen, liver, and small intestine.


:

Pssm-ID: 133303  Cd Length: 158  Bit Score: 297.87  E-value: 1.71e-96
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564359681  71 LRLGVLGDVRSGKSSLIHRFLTGSYQVLEKPESEQYKKEMLVDGQTHLVLIREEAGAPDAKFSGWADAVIFVFSLEDESS 150
Cdd:cd04103    1 LKLGIVGNLRSGKSALVHRYLTGSYVQLESPEGGRFKKEVLVDGQSHLLLIRDEGGAPDAQFAGWVDAVIFVFSLEDEAS 80
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564359681 151 FQAVSHLHGQLISLRgeGRGGLALALVGTQDRISASSPRVVGDARARALCTDMKRCSYYETCATYGLNVDRVFQEVAQKV 230
Cdd:cd04103   81 FQTVYRLYHQLSSYR--NISEIPLILVGTQDAISASNPRVIDDARARQLCADMKRCSYYETCATYGLNVERVFQEAAQKI 158
ArfGap_AGAP cd08836
ArfGAP with GTPase domain, ANK repeat and PH domains; The AGAP subfamily of ADP-ribosylation ...
576-683 7.27e-76

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: 241.43  E-value: 7.27e-76
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564359681 576 VAIQAIRNAKGNSTCVDCGAPNPTWASLNLGALICIECSGIHRNLGTHLSRVRSLDLDDWPRELTLVLTAIGNDTANRVW 655
Cdd:cd08836    1 AALQAIRNVRGNDHCVDCGAPNPDWASLNLGALMCIECSGIHRNLGTHISRVRSLDLDDWPVELLKVMSAIGNDLANSVW 80
                         90       100
                 ....*....|....*....|....*...
gi 564359681 656 ESDTRGRAKPTRDSSREERESWIRAKYE 683
Cdd:cd08836   81 EGNTQGRTKPTPDSSREEKERWIRAKYE 108
PH_AGAP cd01250
Arf-GAP with GTPase, ANK repeat and PH domain-containing protein Pleckstrin homology (PH) ...
338-558 4.20e-56

Arf-GAP with GTPase, ANK repeat and PH domain-containing protein Pleckstrin homology (PH) domain; AGAP (also called centaurin gamma; PIKE/Phosphatidylinositol-3-kinase enhancer) reside mainly in the nucleus and are known to activate phosphoinositide 3-kinase, a key regulator of cell proliferation, motility and vesicular trafficking. There are 3 isoforms of AGAP (PIKE-A, PIKE-L, and PIKE-S) the longest of which PIKE-L consists of N-terminal proline rich domains (PRDs), followed by a GTPase domain, a split PH domain (PHN and PHC), an ArfGAP domain and two ankyrin repeats. PIKE-S terminates after the PHN domain and PIKE-A is missing the PRD region. Centaurin binds phosphatidlyinositol (3,4,5)P3. PH domains have diverse functions, but in general are involved in targeting proteins to the appropriate cellular location or in the interaction with a binding partner. They share little sequence conservation, but all have a common fold, which is electrostatically polarized. Less than 10% of PH domains bind phosphoinositide phosphates (PIPs) with high affinity and specificity. PH domains are distinguished from other PIP-binding domains by their specific high-affinity binding to PIPs with two vicinal phosphate groups: PtdIns(3,4)P2, PtdIns(4,5)P2 or PtdIns(3,4,5)P3 which results in targeting some PH domain proteins to the plasma membrane. A few display strong specificity in lipid binding. Any specificity is usually determined by loop regions or insertions in the N-terminus of the domain, which are not conserved across all PH domains. PH domains are found in cellular signaling proteins such as serine/threonine kinase, tyrosine kinases, regulators of G-proteins, endocytotic GTPases, adaptors, as well as cytoskeletal associated molecules and in lipid associated enzymes.


:

Pssm-ID: 241281  Cd Length: 114  Bit Score: 188.30  E-value: 4.20e-56
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564359681 338 RAIPIKQSFLLKRSGNSLNKEWKKKYVTLSSNGFLLYHPSINDYIHSTHGKEMDLLRTTVKVPGKRPPRAISAfgpsasi 417
Cdd:cd01250    1 RAIPIKQGYLYKRSSKSLNKEWKKKYVTLCDDGRLTYHPSLHDYMENVHGKEIDLLRTTVKVPGKRPPRASSK------- 73
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564359681 418 nglvkdmstvqmgegpeastpmpspspspsslqlptdqtskhllkpdrnlaralstdctpsgdlsplsrepppspmvkkq 497
Cdd:cd01250      --------------------------------------------------------------------------------
                        170       180       190       200       210       220
                 ....*....|....*....|....*....|....*....|....*....|....*....|.
gi 564359681 498 rrkklstpsktegsavqaeeENFEFLIVSSTGQTWHFEAASFEERDAWVQAIESQILASLQ 558
Cdd:cd01250   74 --------------------SAFEFIIVSLDGKQWHFEAASSEERDEWVQAIEQQILASLQ 114
ANKYR COG0666
Ankyrin repeat [Signal transduction mechanisms];
732-791 9.98e-10

Ankyrin repeat [Signal transduction mechanisms];


:

Pssm-ID: 440430 [Multi-domain]  Cd Length: 289  Bit Score: 60.74  E-value: 9.98e-10
                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|
gi 564359681 732 DPQLRSPLHLAAELAHVVITQLLLWYGADVAARDAQGRTALFYARQAGSQLCADILLQHG 791
Cdd:COG0666  150 DNDGNTPLHLAAANGNLEIVKLLLEAGADVNARDNDGETPLHLAAENGHLEIVKLLLEAG 209
 
Name Accession Description Interval E-value
Centaurin_gamma cd04103
Centaurin gamma (CENTG) GTPase; The centaurins (alpha, beta, gamma, and delta) are large, ...
71-230 1.71e-96

Centaurin gamma (CENTG) GTPase; The centaurins (alpha, beta, gamma, and delta) are large, multi-domain proteins that all contain an ArfGAP domain and ankyrin repeats, and in some cases, numerous additional domains. Centaurin gamma contains an additional GTPase domain near its N-terminus. The specific function of this GTPase domain has not been well characterized, but centaurin gamma 2 (CENTG2) may play a role in the development of autism. Centaurin gamma 1 is also called PIKE (phosphatidyl inositol (PI) 3-kinase enhancer) and centaurin gamma 2 is also known as AGAP (ArfGAP protein with a GTPase-like domain, ankyrin repeats and a Pleckstrin homology domain) or GGAP. Three isoforms of PIKE have been identified. PIKE-S (short) and PIKE-L (long) are brain-specific isoforms, with PIKE-S restricted to the nucleus and PIKE-L found in multiple cellular compartments. A third isoform, PIKE-A was identified in human glioblastoma brain cancers and has been found in various tissues. GGAP has been shown to have high GTPase activity due to a direct intramolecular interaction between the N-terminal GTPase domain and the C-terminal ArfGAP domain. In human tissue, AGAP mRNA was detected in skeletal muscle, kidney, placenta, brain, heart, colon, and lung. Reduced expression levels were also observed in the spleen, liver, and small intestine.


Pssm-ID: 133303  Cd Length: 158  Bit Score: 297.87  E-value: 1.71e-96
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564359681  71 LRLGVLGDVRSGKSSLIHRFLTGSYQVLEKPESEQYKKEMLVDGQTHLVLIREEAGAPDAKFSGWADAVIFVFSLEDESS 150
Cdd:cd04103    1 LKLGIVGNLRSGKSALVHRYLTGSYVQLESPEGGRFKKEVLVDGQSHLLLIRDEGGAPDAQFAGWVDAVIFVFSLEDEAS 80
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564359681 151 FQAVSHLHGQLISLRgeGRGGLALALVGTQDRISASSPRVVGDARARALCTDMKRCSYYETCATYGLNVDRVFQEVAQKV 230
Cdd:cd04103   81 FQTVYRLYHQLSSYR--NISEIPLILVGTQDAISASNPRVIDDARARQLCADMKRCSYYETCATYGLNVERVFQEAAQKI 158
ArfGap_AGAP cd08836
ArfGAP with GTPase domain, ANK repeat and PH domains; The AGAP subfamily of ADP-ribosylation ...
576-683 7.27e-76

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: 241.43  E-value: 7.27e-76
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564359681 576 VAIQAIRNAKGNSTCVDCGAPNPTWASLNLGALICIECSGIHRNLGTHLSRVRSLDLDDWPRELTLVLTAIGNDTANRVW 655
Cdd:cd08836    1 AALQAIRNVRGNDHCVDCGAPNPDWASLNLGALMCIECSGIHRNLGTHISRVRSLDLDDWPVELLKVMSAIGNDLANSVW 80
                         90       100
                 ....*....|....*....|....*...
gi 564359681 656 ESDTRGRAKPTRDSSREERESWIRAKYE 683
Cdd:cd08836   81 EGNTQGRTKPTPDSSREEKERWIRAKYE 108
PH_AGAP cd01250
Arf-GAP with GTPase, ANK repeat and PH domain-containing protein Pleckstrin homology (PH) ...
338-558 4.20e-56

Arf-GAP with GTPase, ANK repeat and PH domain-containing protein Pleckstrin homology (PH) domain; AGAP (also called centaurin gamma; PIKE/Phosphatidylinositol-3-kinase enhancer) reside mainly in the nucleus and are known to activate phosphoinositide 3-kinase, a key regulator of cell proliferation, motility and vesicular trafficking. There are 3 isoforms of AGAP (PIKE-A, PIKE-L, and PIKE-S) the longest of which PIKE-L consists of N-terminal proline rich domains (PRDs), followed by a GTPase domain, a split PH domain (PHN and PHC), an ArfGAP domain and two ankyrin repeats. PIKE-S terminates after the PHN domain and PIKE-A is missing the PRD region. Centaurin binds phosphatidlyinositol (3,4,5)P3. PH domains have diverse functions, but in general are involved in targeting proteins to the appropriate cellular location or in the interaction with a binding partner. They share little sequence conservation, but all have a common fold, which is electrostatically polarized. Less than 10% of PH domains bind phosphoinositide phosphates (PIPs) with high affinity and specificity. PH domains are distinguished from other PIP-binding domains by their specific high-affinity binding to PIPs with two vicinal phosphate groups: PtdIns(3,4)P2, PtdIns(4,5)P2 or PtdIns(3,4,5)P3 which results in targeting some PH domain proteins to the plasma membrane. A few display strong specificity in lipid binding. Any specificity is usually determined by loop regions or insertions in the N-terminus of the domain, which are not conserved across all PH domains. PH domains are found in cellular signaling proteins such as serine/threonine kinase, tyrosine kinases, regulators of G-proteins, endocytotic GTPases, adaptors, as well as cytoskeletal associated molecules and in lipid associated enzymes.


Pssm-ID: 241281  Cd Length: 114  Bit Score: 188.30  E-value: 4.20e-56
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564359681 338 RAIPIKQSFLLKRSGNSLNKEWKKKYVTLSSNGFLLYHPSINDYIHSTHGKEMDLLRTTVKVPGKRPPRAISAfgpsasi 417
Cdd:cd01250    1 RAIPIKQGYLYKRSSKSLNKEWKKKYVTLCDDGRLTYHPSLHDYMENVHGKEIDLLRTTVKVPGKRPPRASSK------- 73
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564359681 418 nglvkdmstvqmgegpeastpmpspspspsslqlptdqtskhllkpdrnlaralstdctpsgdlsplsrepppspmvkkq 497
Cdd:cd01250      --------------------------------------------------------------------------------
                        170       180       190       200       210       220
                 ....*....|....*....|....*....|....*....|....*....|....*....|.
gi 564359681 498 rrkklstpsktegsavqaeeENFEFLIVSSTGQTWHFEAASFEERDAWVQAIESQILASLQ 558
Cdd:cd01250   74 --------------------SAFEFIIVSLDGKQWHFEAASSEERDEWVQAIEQQILASLQ 114
ArfGap smart00105
Putative GTP-ase activating proteins for the small GTPase, ARF; Putative zinc fingers with ...
578-695 5.02e-52

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: 177.15  E-value: 5.02e-52
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564359681   578 IQAIRNAKGNSTCVDCGAPNPTWASLNLGALICIECSGIHRNLGTHLSRVRSLDLDDWPRELTLVLTAIGNDTANRVWES 657
Cdd:smart00105   1 LKLLRSIPGNKKCFDCGAPNPTWASVNLGVFLCIECSGIHRSLGVHISKVRSLTLDTWTEEELRLLQKGGNENANSIWES 80
                           90       100       110
                   ....*....|....*....|....*....|....*....
gi 564359681   658 DTRGRAKPTRDSS-REERESWIRAKYEQLLFLAPLGTTE 695
Cdd:smart00105  81 NLDDFSLKPPDDDdQQKYESFIAAKYEEKLFVPPESAEE 119
ArfGap pfam01412
Putative GTPase activating protein for Arf; Putative zinc fingers with GTPase activating ...
577-690 8.34e-51

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: 173.56  E-value: 8.34e-51
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564359681  577 AIQAIRNAKGNSTCVDCGAPNPTWASLNLGALICIECSGIHRNLGTHLSRVRSLDLDDWPRELTLVLTAIGNDTANRVWE 656
Cdd:pfam01412   3 VLRELLKLPGNKVCADCGAPNPTWASVNLGIFICIDCSGVHRSLGVHISKVRSLTLDTWTDEQLELMKAGGNDRANEFWE 82
                          90       100       110
                  ....*....|....*....|....*....|....
gi 564359681  657 SDTRGRAKPTRDSSREERESWIRAKYEQLLFLAP 690
Cdd:pfam01412  83 ANLPPSYKPPPSSDREKRESFIRAKYVEKKFAKP 116
COG5347 COG5347
GTPase-activating protein that regulates ARFs (ADP-ribosylation factors), involved in ...
570-683 3.47e-33

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: 130.67  E-value: 3.47e-33
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564359681 570 DSQSEAVAIQAIRNAKGNSTCVDCGAPNPTWASLNLGALICIECSGIHRNLGTHLSRVRSLDLDDWPRELTLVLTAIGND 649
Cdd:COG5347    3 TKSEDRKLLKLLKSDSSNKKCADCGAPNPTWASVNLGVFLCIDCAGVHRSLGVHISKVKSLTLDNWTEEELRRMEVGGNS 82
                         90       100       110
                 ....*....|....*....|....*....|....*.
gi 564359681 650 TANRVWESD-TRGRAKPTR-DSSREERESWIRAKYE 683
Cdd:COG5347   83 NANRFYEKNlLDQLLLPIKaKYDSSVAKKYIRKKYE 118
PLN03114 PLN03114
ADP-ribosylation factor GTPase-activating protein AGD10; Provisional
587-699 3.78e-15

ADP-ribosylation factor GTPase-activating protein AGD10; Provisional


Pssm-ID: 178661 [Multi-domain]  Cd Length: 395  Bit Score: 78.36  E-value: 3.78e-15
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564359681 587 NSTCVDCGAPNPTWASLNLGALICIECSGIHRNLGTHLSRVRSLDLDDWPRELTLVLTAIGNDTANRV-----WESDTRG 661
Cdd:PLN03114  22 NKICFDCNAKNPTWASVTYGIFLCIDCSAVHRSLGVHISFVRSTNLDSWSSEQLKMMIYGGNNRAQVFfkqygWSDGGKT 101
                         90       100       110       120
                 ....*....|....*....|....*....|....*....|....
gi 564359681 662 RAKPTRDSSREERE----SWIRAKYEQLLFL--APLGTTEEPLG 699
Cdd:PLN03114 102 EAKYTSRAADLYKQilakEVAKSKAEEELDLppSPPDSTQVPNG 145
small_GTPase smart00010
Small GTPase of the Ras superfamily; ill-defined subfamily; SMART predicts Ras-like small ...
69-236 5.99e-13

Small GTPase of the Ras superfamily; ill-defined subfamily; SMART predicts Ras-like small GTPases of the ARF, RAB, RAN, RAS, and SAR subfamilies. Others that could not be classified in this way are predicted to be members of the small GTPase superfamily without predictions of the subfamily.


Pssm-ID: 197466 [Multi-domain]  Cd Length: 166  Bit Score: 67.59  E-value: 5.99e-13
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564359681    69 PELRLGVLGDVRSGKSSLIHRFLTGSYqvLEK--PESE-QYKKEMLVDGQTHLVLIREEAGapDAKFSGWAD-------A 138
Cdd:smart00010   1 REYKLVVLGGGGVGKSALTIQFVQGHF--VDEydPTIEdSYRKQIEIDGEVCLLDILDTAG--QEEFSAMRDqymrtgeG 76
                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564359681   139 VIFVFSLEDESSFQAVSHLHGQLisLRGEGRGGLALALVGTQ-DRISAsspRVVGDARARALCTDMKrCSYYETCATYGL 217
Cdd:smart00010  77 FLLVYSITDRQSFEEIAKFREQI--LRVKDRDDVPIVLVGNKcDLENE---RVVSTEEGKELARQWG-CPFLETSAKERI 150
                          170
                   ....*....|....*....
gi 564359681   218 NVDRVFQEVaqkVVTLRKQ 236
Cdd:smart00010 151 NVDEAFYDL---VREIRKS 166
Ras pfam00071
Ras family; Includes sub-families Ras, Rab, Rac, Ral, Ran, Rap Ypt1 and more. Shares P-loop ...
75-230 9.40e-13

Ras family; Includes sub-families Ras, Rab, Rac, Ral, Ran, Rap Ypt1 and more. Shares P-loop motif with GTP_EFTU, arf and myosin_head. See pfam00009 pfam00025, pfam00063. As regards Rab GTPases, these are important regulators of vesicle formation, motility and fusion. They share a fold in common with all Ras GTPases: this is a six-stranded beta-sheet surrounded by five alpha-helices.


Pssm-ID: 425451 [Multi-domain]  Cd Length: 162  Bit Score: 66.77  E-value: 9.40e-13
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564359681   75 VLGDVRSGKSSLIHRFLTGSYQvlEKPES----EQYKKEMLVDGQTHLVLIREEAGA------PDAKFSGwADAVIFVFS 144
Cdd:pfam00071   4 LVGDGGVGKSSLLIRFTQNKFP--EEYIPtigvDFYTKTIEVDGKTVKLQIWDTAGQerfralRPLYYRG-ADGFLLVYD 80
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564359681  145 LEDESSFQAVSHLHGQLISLRGEgrgGLALALVGTQdrISASSPRVVGDARARALCTDMKrCSYYETCATYGLNVDRVFQ 224
Cdd:pfam00071  81 ITSRDSFENVKKWVEEILRHADE---NVPIVLVGNK--CDLEDQRVVSTEEGEALAKELG-LPFMETSAKTNENVEEAFE 154

                  ....*.
gi 564359681  225 EVAQKV 230
Cdd:pfam00071 155 ELAREI 160
ANKYR COG0666
Ankyrin repeat [Signal transduction mechanisms];
732-791 9.98e-10

Ankyrin repeat [Signal transduction mechanisms];


Pssm-ID: 440430 [Multi-domain]  Cd Length: 289  Bit Score: 60.74  E-value: 9.98e-10
                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|
gi 564359681 732 DPQLRSPLHLAAELAHVVITQLLLWYGADVAARDAQGRTALFYARQAGSQLCADILLQHG 791
Cdd:COG0666  150 DNDGNTPLHLAAANGNLEIVKLLLEAGADVNARDNDGETPLHLAAENGHLEIVKLLLEAG 209
Gem1 COG1100
GTPase SAR1 family domain [General function prediction only];
70-228 9.16e-09

GTPase SAR1 family domain [General function prediction only];


Pssm-ID: 440717 [Multi-domain]  Cd Length: 177  Bit Score: 55.76  E-value: 9.16e-09
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564359681  70 ELRLGVLGDVRSGKSSLIHRFLTGSYQvLEKPES----EQYKKEMLVDGQT-HLVLI----REEAGAPDAKFSGW---AD 137
Cdd:COG1100    3 EKKIVVVGTGGVGKTSLVNRLVGDIFS-LEKYLStngvTIDKKELKLDGLDvDLVIWdtpgQDEFRETRQFYARQltgAS 81
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564359681 138 AVIFVFSLEDESSFQAVSHLHGQLISLRGEGRgglaLALVGTQ-DRISAssPRVVGDARARALCTDMKRCSYYETCATYG 216
Cdd:COG1100   82 LYLFVVDGTREETLQSLYELLESLRRLGKKSP----IILVLNKiDLYDE--EEIEDEERLKEALSEDNIVEVVATSAKTG 155
                        170
                 ....*....|..
gi 564359681 217 LNVDRVFQEVAQ 228
Cdd:COG1100  156 EGVEELFAALAE 167
Ank_2 pfam12796
Ankyrin repeats (3 copies);
739-790 2.82e-07

Ankyrin repeats (3 copies);


Pssm-ID: 463710 [Multi-domain]  Cd Length: 91  Bit Score: 48.96  E-value: 2.82e-07
                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|..
gi 564359681  739 LHLAAELAHVVITQLLLWYGADVAARDAQGRTALFYARQAGSQLCADILLQH 790
Cdd:pfam12796   1 LHLAAKNGNLELVKLLLENGADANLQDKNGRTALHLAAKNGHLEIVKLLLEH 52
PLN03118 PLN03118
Rab family protein; Provisional
75-231 1.08e-05

Rab family protein; Provisional


Pssm-ID: 215587 [Multi-domain]  Cd Length: 211  Bit Score: 47.36  E-value: 1.08e-05
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564359681  75 VLGDVRSGKSSLIHRFLTGSYQVLEKPESEQYK-KEMLVDGQTHLVLIREEAGAP-----DAKFSGWADAVIFVFSLEDE 148
Cdd:PLN03118  19 LIGDSGVGKSSLLVSFISSSVEDLAPTIGVDFKiKQLTVGGKRLKLTIWDTAGQErfrtlTSSYYRNAQGIILVYDVTRR 98
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564359681 149 SSFQAVSHLHGQLISLRGEGRGGLALaLVGtqDRISASSPRVVGDARARALCTDMKrCSYYETCATYGLNVDRVFQEVAQ 228
Cdd:PLN03118  99 ETFTNLSDVWGKEVELYSTNQDCVKM-LVG--NKVDRESERDVSREEGMALAKEHG-CLFLECSAKTRENVEQCFEELAL 174

                 ...
gi 564359681 229 KVV 231
Cdd:PLN03118 175 KIM 177
PTZ00322 PTZ00322
6-phosphofructo-2-kinase/fructose-2,6-biphosphatase; Provisional
724-797 2.67e-05

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


Pssm-ID: 140343 [Multi-domain]  Cd Length: 664  Bit Score: 47.97  E-value: 2.67e-05
                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 564359681 724 GPLDTSVEDPQLRSPLHLAAELAHVVITQLLLWYGADVAARDAQGRTALFYARQAGSQLCADILLQHG-CPGEGG 797
Cdd:PTZ00322 104 GGADPNCRDYDGRTPLHIACANGHVQVVRVLLEFGADPTLLDKDGKTPLELAEENGFREVVQLLSRHSqCHFELG 178
PH smart00233
Pleckstrin homology domain; Domain commonly found in eukaryotic signalling proteins. The ...
516-553 6.67e-05

Pleckstrin homology domain; Domain commonly found in eukaryotic signalling proteins. The domain family possesses multiple functions including the abilities to bind inositol phosphates, and various proteins. PH domains have been found to possess inserted domains (such as in PLC gamma, syntrophins) and to be inserted within other domains. Mutations in Brutons tyrosine kinase (Btk) within its PH domain cause X-linked agammaglobulinaemia (XLA) in patients. Point mutations cluster into the positively charged end of the molecule around the predicted binding site for phosphatidylinositol lipids.


Pssm-ID: 214574 [Multi-domain]  Cd Length: 102  Bit Score: 42.54  E-value: 6.67e-05
                           10        20        30
                   ....*....|....*....|....*....|....*...
gi 564359681   516 EEENFEFLIVSSTGQTWHFEAASFEERDAWVQAIESQI 553
Cdd:smart00233  64 SKKPHCFEIKTSDRKTLLLQAESEEEREKWVEALRKAI 101
 
Name Accession Description Interval E-value
Centaurin_gamma cd04103
Centaurin gamma (CENTG) GTPase; The centaurins (alpha, beta, gamma, and delta) are large, ...
71-230 1.71e-96

Centaurin gamma (CENTG) GTPase; The centaurins (alpha, beta, gamma, and delta) are large, multi-domain proteins that all contain an ArfGAP domain and ankyrin repeats, and in some cases, numerous additional domains. Centaurin gamma contains an additional GTPase domain near its N-terminus. The specific function of this GTPase domain has not been well characterized, but centaurin gamma 2 (CENTG2) may play a role in the development of autism. Centaurin gamma 1 is also called PIKE (phosphatidyl inositol (PI) 3-kinase enhancer) and centaurin gamma 2 is also known as AGAP (ArfGAP protein with a GTPase-like domain, ankyrin repeats and a Pleckstrin homology domain) or GGAP. Three isoforms of PIKE have been identified. PIKE-S (short) and PIKE-L (long) are brain-specific isoforms, with PIKE-S restricted to the nucleus and PIKE-L found in multiple cellular compartments. A third isoform, PIKE-A was identified in human glioblastoma brain cancers and has been found in various tissues. GGAP has been shown to have high GTPase activity due to a direct intramolecular interaction between the N-terminal GTPase domain and the C-terminal ArfGAP domain. In human tissue, AGAP mRNA was detected in skeletal muscle, kidney, placenta, brain, heart, colon, and lung. Reduced expression levels were also observed in the spleen, liver, and small intestine.


Pssm-ID: 133303  Cd Length: 158  Bit Score: 297.87  E-value: 1.71e-96
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564359681  71 LRLGVLGDVRSGKSSLIHRFLTGSYQVLEKPESEQYKKEMLVDGQTHLVLIREEAGAPDAKFSGWADAVIFVFSLEDESS 150
Cdd:cd04103    1 LKLGIVGNLRSGKSALVHRYLTGSYVQLESPEGGRFKKEVLVDGQSHLLLIRDEGGAPDAQFAGWVDAVIFVFSLEDEAS 80
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564359681 151 FQAVSHLHGQLISLRgeGRGGLALALVGTQDRISASSPRVVGDARARALCTDMKRCSYYETCATYGLNVDRVFQEVAQKV 230
Cdd:cd04103   81 FQTVYRLYHQLSSYR--NISEIPLILVGTQDAISASNPRVIDDARARQLCADMKRCSYYETCATYGLNVERVFQEAAQKI 158
ArfGap_AGAP cd08836
ArfGAP with GTPase domain, ANK repeat and PH domains; The AGAP subfamily of ADP-ribosylation ...
576-683 7.27e-76

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: 241.43  E-value: 7.27e-76
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564359681 576 VAIQAIRNAKGNSTCVDCGAPNPTWASLNLGALICIECSGIHRNLGTHLSRVRSLDLDDWPRELTLVLTAIGNDTANRVW 655
Cdd:cd08836    1 AALQAIRNVRGNDHCVDCGAPNPDWASLNLGALMCIECSGIHRNLGTHISRVRSLDLDDWPVELLKVMSAIGNDLANSVW 80
                         90       100
                 ....*....|....*....|....*...
gi 564359681 656 ESDTRGRAKPTRDSSREERESWIRAKYE 683
Cdd:cd08836   81 EGNTQGRTKPTPDSSREEKERWIRAKYE 108
ArfGap_AGAP1 cd08854
ArfGAP with GTPase domain, ANK repeat and PH domain 1; The AGAP subfamily of ADP-ribosylation ...
575-683 3.69e-73

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: 234.13  E-value: 3.69e-73
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564359681 575 AVAIQAIRNAKGNSTCVDCGAPNPTWASLNLGALICIECSGIHRNLGTHLSRVRSLDLDDWPRELTLVLTAIGNDTANRV 654
Cdd:cd08854    1 AVAIQAIRNAKGNSLCVDCGAPNPTWASLNLGALICIECSGIHRNLGTHLSRVRSLDLDDWPRELTLVLTAIGNHMANSI 80
                         90       100
                 ....*....|....*....|....*....
gi 564359681 655 WESDTRGRAKPTRDSSREERESWIRAKYE 683
Cdd:cd08854   81 WESCTQGRTKPAPDSSREERESWIRAKYE 109
ArfGap_AGAP3 cd08855
ArfGAP with GTPase domain, ANK repeat and PH domain 3; The AGAP subfamily of ADP-ribosylation ...
574-683 5.18e-62

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: 204.13  E-value: 5.18e-62
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564359681 574 EAVAIQAIRNAKGNSTCVDCGAPNPTWASLNLGALICIECSGIHRNLGTHLSRVRSLDLDDWPRELTLVLTAIGNDTANR 653
Cdd:cd08855    1 DALAIQSIRNVRGNSFCIDCDAPNPDWASLNLGALMCIECSGIHRNLGTHLSRVRSLDLDDWPVELSMVMTAIGNAMANS 80
                         90       100       110
                 ....*....|....*....|....*....|
gi 564359681 654 VWESDTRGRAKPTRDSSREERESWIRAKYE 683
Cdd:cd08855   81 VWEGALDGYSKPGPDSTREEKERWIRAKYE 110
ArfGap_AGAP2 cd08853
ArfGAP with GTPase domain, ANK repeat and PH domain 2; The AGAP subfamily of ADP-ribosylation ...
575-683 6.17e-59

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


Pssm-ID: 350078 [Multi-domain]  Cd Length: 109  Bit Score: 196.00  E-value: 6.17e-59
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564359681 575 AVAIQAIRNAKGNSTCVDCGAPNPTWASLNLGALICIECSGIHRNLGTHLSRVRSLDLDDWPRELTLVLTAIGNDTANRV 654
Cdd:cd08853    1 AMALQSIRNMRGNSHCVDCETQNPKWASLNLGVLMCIECSGIHRNLGTHLSRVRSLDLDDWPVELRKVMSSIGNELANSI 80
                         90       100
                 ....*....|....*....|....*....
gi 564359681 655 WESDTRGRAKPTRDSSREERESWIRAKYE 683
Cdd:cd08853   81 WEGSSQGQTKPSSDSTREEKERWIRAKYE 109
PH_AGAP cd01250
Arf-GAP with GTPase, ANK repeat and PH domain-containing protein Pleckstrin homology (PH) ...
338-558 4.20e-56

Arf-GAP with GTPase, ANK repeat and PH domain-containing protein Pleckstrin homology (PH) domain; AGAP (also called centaurin gamma; PIKE/Phosphatidylinositol-3-kinase enhancer) reside mainly in the nucleus and are known to activate phosphoinositide 3-kinase, a key regulator of cell proliferation, motility and vesicular trafficking. There are 3 isoforms of AGAP (PIKE-A, PIKE-L, and PIKE-S) the longest of which PIKE-L consists of N-terminal proline rich domains (PRDs), followed by a GTPase domain, a split PH domain (PHN and PHC), an ArfGAP domain and two ankyrin repeats. PIKE-S terminates after the PHN domain and PIKE-A is missing the PRD region. Centaurin binds phosphatidlyinositol (3,4,5)P3. PH domains have diverse functions, but in general are involved in targeting proteins to the appropriate cellular location or in the interaction with a binding partner. They share little sequence conservation, but all have a common fold, which is electrostatically polarized. Less than 10% of PH domains bind phosphoinositide phosphates (PIPs) with high affinity and specificity. PH domains are distinguished from other PIP-binding domains by their specific high-affinity binding to PIPs with two vicinal phosphate groups: PtdIns(3,4)P2, PtdIns(4,5)P2 or PtdIns(3,4,5)P3 which results in targeting some PH domain proteins to the plasma membrane. A few display strong specificity in lipid binding. Any specificity is usually determined by loop regions or insertions in the N-terminus of the domain, which are not conserved across all PH domains. PH domains are found in cellular signaling proteins such as serine/threonine kinase, tyrosine kinases, regulators of G-proteins, endocytotic GTPases, adaptors, as well as cytoskeletal associated molecules and in lipid associated enzymes.


Pssm-ID: 241281  Cd Length: 114  Bit Score: 188.30  E-value: 4.20e-56
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564359681 338 RAIPIKQSFLLKRSGNSLNKEWKKKYVTLSSNGFLLYHPSINDYIHSTHGKEMDLLRTTVKVPGKRPPRAISAfgpsasi 417
Cdd:cd01250    1 RAIPIKQGYLYKRSSKSLNKEWKKKYVTLCDDGRLTYHPSLHDYMENVHGKEIDLLRTTVKVPGKRPPRASSK------- 73
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564359681 418 nglvkdmstvqmgegpeastpmpspspspsslqlptdqtskhllkpdrnlaralstdctpsgdlsplsrepppspmvkkq 497
Cdd:cd01250      --------------------------------------------------------------------------------
                        170       180       190       200       210       220
                 ....*....|....*....|....*....|....*....|....*....|....*....|.
gi 564359681 498 rrkklstpsktegsavqaeeENFEFLIVSSTGQTWHFEAASFEERDAWVQAIESQILASLQ 558
Cdd:cd01250   74 --------------------SAFEFIIVSLDGKQWHFEAASSEERDEWVQAIEQQILASLQ 114
ArfGap cd08204
GTPase-activating protein (GAP) for the ADP ribosylation factors (ARFs); ArfGAPs are a family ...
578-682 1.25e-52

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: 178.08  E-value: 1.25e-52
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564359681 578 IQAIRNAKGNSTCVDCGAPNPTWASLNLGALICIECSGIHRNLGTHLSRVRSLDLDDWPRELTLVLTAIGNDTANRVWES 657
Cdd:cd08204    1 LEELLKLPGNKVCADCGAPDPRWASINLGVFICIRCSGIHRSLGVHISKVRSLTLDSWTPEQVELMKAIGNARANAYYEA 80
                         90       100
                 ....*....|....*....|....*.
gi 564359681 658 D-TRGRAKPTRDSSREERESWIRAKY 682
Cdd:cd08204   81 NlPPGFKKPTPDSSDEEREQFIRAKY 106
ArfGap smart00105
Putative GTP-ase activating proteins for the small GTPase, ARF; Putative zinc fingers with ...
578-695 5.02e-52

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: 177.15  E-value: 5.02e-52
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564359681   578 IQAIRNAKGNSTCVDCGAPNPTWASLNLGALICIECSGIHRNLGTHLSRVRSLDLDDWPRELTLVLTAIGNDTANRVWES 657
Cdd:smart00105   1 LKLLRSIPGNKKCFDCGAPNPTWASVNLGVFLCIECSGIHRSLGVHISKVRSLTLDTWTEEELRLLQKGGNENANSIWES 80
                           90       100       110
                   ....*....|....*....|....*....|....*....
gi 564359681   658 DTRGRAKPTRDSS-REERESWIRAKYEQLLFLAPLGTTE 695
Cdd:smart00105  81 NLDDFSLKPPDDDdQQKYESFIAAKYEEKLFVPPESAEE 119
ArfGap pfam01412
Putative GTPase activating protein for Arf; Putative zinc fingers with GTPase activating ...
577-690 8.34e-51

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: 173.56  E-value: 8.34e-51
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564359681  577 AIQAIRNAKGNSTCVDCGAPNPTWASLNLGALICIECSGIHRNLGTHLSRVRSLDLDDWPRELTLVLTAIGNDTANRVWE 656
Cdd:pfam01412   3 VLRELLKLPGNKVCADCGAPNPTWASVNLGIFICIDCSGVHRSLGVHISKVRSLTLDTWTDEQLELMKAGGNDRANEFWE 82
                          90       100       110
                  ....*....|....*....|....*....|....
gi 564359681  657 SDTRGRAKPTRDSSREERESWIRAKYEQLLFLAP 690
Cdd:pfam01412  83 ANLPPSYKPPPSSDREKRESFIRAKYVEKKFAKP 116
ArfGap_ACAP cd08835
ArfGAP domain of ACAP (ArfGAP with Coiled-coil, ANK repeat and PH domains) proteins; ArfGAP ...
576-688 1.09e-44

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: 156.26  E-value: 1.09e-44
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564359681 576 VAIQAIRNAKGNSTCVDCGAPNPTWASLNLGALICIECSGIHRNLGTHLSRVRSLDLDDWPRELTLVLTAIGNDTANRVW 655
Cdd:cd08835    2 SALEQVLSVPGNAQCCDCGSPDPRWASINLGVTLCIECSGIHRSLGVHVSKVRSLTLDSWEPELLKVMLELGNDVVNRIY 81
                         90       100       110
                 ....*....|....*....|....*....|....*
gi 564359681 656 ES--DTRGRAKPTRDSSREERESWIRAKYEQLLFL 688
Cdd:cd08835   82 EAnvPDDGSVKPTPDSSRQEREAWIRAKYVEKKFV 116
ArfGap_ASAP cd08834
ArfGAP domain of ASAP (Arf GAP, SH3, ANK repeat and PH domains) subfamily of ADP-ribosylation ...
578-682 1.36e-41

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: 147.75  E-value: 1.36e-41
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564359681 578 IQAIRNAKGNSTCVDCGAPNPTWASLNLGALICIECSGIHRNLGTHLSRVRSLDLDDWPRELTLVLTAIGNDTANRVWES 657
Cdd:cd08834    6 IAEVKRLPGNDVCCDCGSPDPTWLSTNLGILTCIECSGVHRELGVHVSRIQSLTLDNLGTSELLLARNLGNEGFNEIMEA 85
                         90       100
                 ....*....|....*....|....*
gi 564359681 658 DTRGRAKPTRDSSREERESWIRAKY 682
Cdd:cd08834   86 NLPPGYKPTPNSDMEERKDFIRAKY 110
ArfGap_ACAP3 cd08850
ArfGAP domain of ACAP3 (ArfGAP with Coiled-coil, ANK repeat and PH domains 3); ACAP3 belongs ...
578-688 9.97e-40

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: 142.39  E-value: 9.97e-40
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564359681 578 IQAIRNAKGNSTCVDCGAPNPTWASLNLGALICIECSGIHRNLGTHLSRVRSLDLDDWPRELTLVLTAIGNDTANRVWE- 656
Cdd:cd08850    4 LQRVQSIAGNDQCCDCGQPDPRWASINLGILLCIECSGIHRSLGVHCSKVRSLTLDSWEPELLKLMCELGNSTVNQIYEa 83
                         90       100       110
                 ....*....|....*....|....*....|...
gi 564359681 657 -SDTRGRAKPTRDSSREERESWIRAKYEQLLFL 688
Cdd:cd08850   84 qCEELGLKKPTASSSRQDKEAWIKAKYVEKKFL 116
ArfGap_ACAP1 cd08852
ArfGAP domain of ACAP1 (ArfGAP with Coiled-coil, ANK repeat and PH domains 1); ACAP1 belongs ...
577-691 4.05e-37

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: 135.09  E-value: 4.05e-37
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564359681 577 AIQAIRNAKGNSTCVDCGAPNPTWASLNLGALICIECSGIHRNLGTHLSRVRSLDLDDWPRELTLVLTAIGNDTANRVWE 656
Cdd:cd08852    3 AVAQVQSVDGNAQCCDCREPAPEWASINLGVTLCIQCSGIHRSLGVHFSKVRSLTLDSWEPELVKLMCELGNVIINQIYE 82
                         90       100       110
                 ....*....|....*....|....*....|....*..
gi 564359681 657 S--DTRGRAKPTRDSSREERESWIRAKYEQLLFLAPL 691
Cdd:cd08852   83 AriEAMAIKKPGPSSSRQEKEAWIRAKYVEKKFITKL 119
ArfGap_ADAP cd08832
ArfGap with dual PH domains; The ADAP subfamily, ArfGAPs with dual pleckstrin homology (PH) ...
585-682 1.34e-36

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: 133.54  E-value: 1.34e-36
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564359681 585 KGNSTCVDCGAPNPTWASLNLGALICIECSGIHRNLGTHLSRVRSLDLDDWPRELTLVLTAIGNDTANRVWE----SDTR 660
Cdd:cd08832   15 PGNNTCADCGAPDPEWASYNLGVFICLDCSGIHRSLGTHISKVKSLRLDNWDDSQVEFMEENGNEKAKAKYEahvpAFYR 94
                         90       100
                 ....*....|....*....|..
gi 564359681 661 graKPTRDSSREERESWIRAKY 682
Cdd:cd08832   95 ---RPTPTDPQVLREQWIRAKY 113
ArfGap_ACAP2 cd08851
ArfGAP domain of ACAP2 (ArfGAP with Coiled-coil, ANK repeat and PH domains 2); ACAP2 belongs ...
577-682 9.99e-36

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: 131.26  E-value: 9.99e-36
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564359681 577 AIQAIRNAKGNSTCVDCGAPNPTWASLNLGALICIECSGIHRNLGTHLSRVRSLDLDDWPRELTLVLTAIGNDTANRVWE 656
Cdd:cd08851    3 ALQRVQCIPGNASCCDCGLADPRWASINLGITLCIECSGIHRSLGVHFSKVRSLTLDTWEPELLKLMCELGNDVINRIYE 82
                         90       100
                 ....*....|....*....|....*...
gi 564359681 657 S--DTRGRAKPTRDSSREERESWIRAKY 682
Cdd:cd08851   83 ArvEKMGAKKPQPGGQRQEKEAYIRAKY 110
ArfGap_SMAP cd08839
Stromal membrane-associated proteins; a subfamily of the ArfGAP family; The SMAP subfamily of ...
586-682 1.96e-34

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: 127.00  E-value: 1.96e-34
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564359681 586 GNSTCVDCGAPNPTWASLNLGALICIECSGIHRNLGTHLSRVRSLDLDDWPRELTLVLTAIGNDTANRVWESD-TRGRAK 664
Cdd:cd08839    9 DNKYCADCGAKGPRWASWNLGVFICIRCAGIHRNLGVHISKVKSVNLDSWTPEQVQSMQEMGNARANAYYEANlPDGFRR 88
                         90
                 ....*....|....*...
gi 564359681 665 PTRDSSreeRESWIRAKY 682
Cdd:cd08839   89 PQTDSA---LENFIRDKY 103
COG5347 COG5347
GTPase-activating protein that regulates ARFs (ADP-ribosylation factors), involved in ...
570-683 3.47e-33

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: 130.67  E-value: 3.47e-33
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564359681 570 DSQSEAVAIQAIRNAKGNSTCVDCGAPNPTWASLNLGALICIECSGIHRNLGTHLSRVRSLDLDDWPRELTLVLTAIGND 649
Cdd:COG5347    3 TKSEDRKLLKLLKSDSSNKKCADCGAPNPTWASVNLGVFLCIDCAGVHRSLGVHISKVKSLTLDNWTEEELRRMEVGGNS 82
                         90       100       110
                 ....*....|....*....|....*....|....*.
gi 564359681 650 TANRVWESD-TRGRAKPTR-DSSREERESWIRAKYE 683
Cdd:COG5347   83 NANRFYEKNlLDQLLLPIKaKYDSSVAKKYIRKKYE 118
ArfGap_GIT cd08833
The GIT subfamily of ADP-ribosylation factor GTPase-activating proteins; The GIT (G-protein ...
581-682 5.79e-32

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: 120.10  E-value: 5.79e-32
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564359681 581 IRNAKGNS-TCVDCGAPNPTWASLNLGALICIECSGIHRNLGTHLSRVRSLDLDDWPRELTLVLTAIGNDTANRVWE--- 656
Cdd:cd08833    1 IRGKSSNArVCADCSAPDPEWASINRGVLICDECCSIHRSLGRHISQVKSLRKDQWPPSLLEMVQTLGNNGANSIWEhsl 80
                         90       100
                 ....*....|....*....|....*....
gi 564359681 657 ---SDTRGRAKPTRDSSREERESWIRAKY 682
Cdd:cd08833   81 ldpSQSGKRKPIPPDPVHPTKEEFIKAKY 109
ArfGap_ArfGap1 cd08830
Arf1 GTPase-activating protein 1; ArfGAP (ADP Ribosylation Factor GTPase Activating Protein) ...
579-657 1.67e-30

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: 116.06  E-value: 1.67e-30
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564359681 579 QAIRNAKGNSTCVDCGAPNPTWASLNLGALICIECSGIHRNLGTHLSRVRSLDLDDW-PRELTLvLTAIGNDTANRVWES 657
Cdd:cd08830    6 RELQKLPGNNRCFDCGAPNPQWASVSYGIFICLECSGVHRGLGVHISFVRSITMDSWsEKQLKK-MELGGNAKLREFFES 84
ArfGap_ARAP cd08837
ArfGap with Rho-Gap domain, ANK repeat and PH domain-containing proteins; The ARAP subfamily ...
575-687 2.69e-29

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: 112.85  E-value: 2.69e-29
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564359681 575 AVAiQAIRNAKGNSTCVDCGAPNPTWASLNLGALICIECSGIHRNLGTHLSRVRSLDLDD--WPRELTLVLTAIGNDTAN 652
Cdd:cd08837    2 EVA-EKIWSNPANRFCADCGAPDPDWASINLCVVICKQCAGEHRSLGSNISKVRSLKMDTkvWTEELVELFLKLGNDRAN 80
                         90       100       110
                 ....*....|....*....|....*....|....*
gi 564359681 653 RVWESDTRGRAKPTRDSSREERESWIRAKYEQLLF 687
Cdd:cd08837   81 RFWAANLPPSEALHPDADSEQRREFITAKYREGKY 115
ArfGap_ASAP3 cd17900
ArfGAP domain of ASAP3 (ArfGAP with ANK repeat and PH domain-containing protein 3); The ...
578-682 3.88e-29

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: 112.63  E-value: 3.88e-29
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564359681 578 IQAIRNAKGNSTCVDCGAPNPTWASLNLGALICIECSGIHRNLGTHLSRVRSLDLDDW-PRELTLVLTaIGNDTANRVWE 656
Cdd:cd17900    6 IAEVKSRPGNSQCCDCGAPDPTWLSTNLGILTCIECSGIHRELGVRYSRIQSLTLDLLsTSELLLAVS-MGNTRFNEVME 84
                         90       100
                 ....*....|....*....|....*...
gi 564359681 657 SD--TRGRAKPTRDSSREERESWIRAKY 682
Cdd:cd17900   85 ATlpAHGGPKPSAESDMGTRKDYIMAKY 112
ArfGap_ArfGap2_3_like cd08831
Arf1 GTPase-activating protein 2/3-like; ArfGAP (ADP Ribosylation Factor GTPase Activating ...
582-657 1.36e-28

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: 110.71  E-value: 1.36e-28
                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 564359681 582 RNAKGNSTCVDCGAPNPTWASLNLGALICIECSGIHRNLGTHLSRVRSLDLDDWPRELTLVLTAIGNDTANRVWES 657
Cdd:cd08831   10 RSKPENKVCFDCGAKNPTWASVTFGVFLCLDCSGVHRSLGVHISFVRSTNLDSWTPEQLRRMKVGGNAKAREFFKQ 85
ArfGap_ASAP1 cd08848
ArfGAP domain of ASAP1 (ArfGAP with SH3 domain, ANK repeat and PH domain-containing protein 1); ...
578-682 3.02e-28

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: 110.12  E-value: 3.02e-28
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564359681 578 IQAIRNAKGNSTCVDCGAPNPTWASLNLGALICIECSGIHRNLGTHLSRVRSLDLDDWPRELTLVLTAIGNDTANRVWES 657
Cdd:cd08848    6 IDDVQRLPGNEVCCDCGSPDPTWLSTNLGILTCIECSGIHREMGVHISRIQSLELDKLGTSELLLAKNVGNNSFNDIMEG 85
                         90       100
                 ....*....|....*....|....*.
gi 564359681 658 DTRG-RAKPTRDSSREERESWIRAKY 682
Cdd:cd08848   86 NLPSpSPKPSPSSDMTARKEYITAKY 111
ArfGap_ArfGap1_like cd08959
ARF1 GTPase-activating protein 1-like; ArfGAP (ADP Ribosylation Factor GTPase Activating ...
578-657 3.12e-28

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: 109.52  E-value: 3.12e-28
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564359681 578 IQAIRNAKGNSTCVDCGAPNPTWASLNLGALICIECSGIHRNLGTHLSRVRSLDLDDWPRELTLVLTAIGNDTANRVWES 657
Cdd:cd08959    5 FKKLRSKPENKVCFDCGAKNPQWASVTYGIFICLDCSGVHRGLGVHISFVRSTTMDKWTEEQLRKMKVGGNANAREFFKQ 84
ArfGap_ADAP1 cd08843
ADAP1 GTPase activating protein for Arf, with dual PH domains; The ADAP subfamily, ArfGAPs ...
586-682 5.53e-26

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: 103.16  E-value: 5.53e-26
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564359681 586 GNSTCVDCGAPNPTWASLNLGALICIECSGIHRNLgTHLSRVRSLDLDDWPRELTLVLTAIGNDTANRVWESDTRG-RAK 664
Cdd:cd08843   16 GNARCADCGAPDPDWASYTLGVFICLSCSGIHRNI-PQVSKVKSVRLDAWEEAQVEFMASHGNDAARARFESKVPSfYYR 94
                         90
                 ....*....|....*...
gi 564359681 665 PTRDSSREERESWIRAKY 682
Cdd:cd08843   95 PTPSDCQLLREQWIRAKY 112
ArfGap_ASAP2 cd08849
ArfGAP domain of ASAP2 (ArfGAP2 with SH3 domain, ANK repeat and PH domain-containing protein 2) ...
578-682 1.81e-25

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: 101.98  E-value: 1.81e-25
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564359681 578 IQAIRNAKGNSTCVDCGAPNPTWASLNLGALICIECSGIHRNLGTHLSRVRSLDLDDWPRELTLVLTAIGNDTANRVWES 657
Cdd:cd08849    6 ISEVQRMTGNDVCCDCGAPDPTWLSTNLGILTCIECSGIHRELGVHYSRMQSLTLDVLGTSELLLAKNIGNAGFNEIMEA 85
                         90       100
                 ....*....|....*....|....*..
gi 564359681 658 --DTRGRAKPTRDSSREERESWIRAKY 682
Cdd:cd08849   86 clPAEDVVKPNPGSDMNARKDYITAKY 112
ArfGap_SMAP2 cd08859
Stromal membrane-associated protein 2; a subfamily of the ArfGAP family; The SMAP subfamily of ...
587-684 2.22e-25

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


Pssm-ID: 350083 [Multi-domain]  Cd Length: 107  Bit Score: 101.22  E-value: 2.22e-25
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564359681 587 NSTCVDCGAPNPTWASLNLGALICIECSGIHRNLGTHLSRVRSLDLDDWPRELTLVLTAIGNDTANRVWES---DTRGRa 663
Cdd:cd08859   10 NKFCADCQSKGPRWASWNIGVFICIRCAGIHRNLGVHISRVKSVNLDQWTQEQIQCMQEMGNGKANRLYEAflpENFRR- 88
                         90       100
                 ....*....|....*....|.
gi 564359681 664 kPTRDSSreeRESWIRAKYEQ 684
Cdd:cd08859   89 -PQTDQA---VEGFIRDKYEK 105
ArfGap_ARAP1 cd17901
ArfGap with Rho-Gap domain, ANK repeat and PH domain-containing protein 1; The ARAP subfamily ...
579-684 5.78e-25

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: 100.27  E-value: 5.78e-25
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564359681 579 QAIRNAKGNSTCVDCGAPNPTWASLNLGALICIECSGIHRNLGTHLSRVRSLDLDD--WPRELTLVLTAIGNDTANRVWE 656
Cdd:cd17901    5 EKIWSVESNRFCADCGSPKPDWASVNLCVVICKRCAGEHRGLGPSVSKVRSLKMDRkvWTEELIELFLLLGNGKANQFWA 84
                         90       100
                 ....*....|....*....|....*...
gi 564359681 657 SDTRGRAKPTRDSSREERESWIRAKYEQ 684
Cdd:cd17901   85 ANVPPSEALCPSSSSEERRHFITAKYKE 112
ArfGap_ADAP2 cd08844
ADAP2 GTPase activating protein for Arf, with dual PH domains; The ADAP subfamily, ArfGAPs ...
586-682 1.89e-23

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: 95.99  E-value: 1.89e-23
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564359681 586 GNSTCVDCGAPNPTWASLNLGALICIECSGIHRNLgTHLSRVRSLDLDDWPRELTLVLTAIGNDTANRVWESDTRG-RAK 664
Cdd:cd08844   16 GNSVCADCGAPDPDWASYTLGIFICLNCSGVHRNL-PDISRVKSIRLDFWEDELVEFMKENGNLKAKAKFEAFVPPfYYR 94
                         90
                 ....*....|....*...
gi 564359681 665 PTRDSSREERESWIRAKY 682
Cdd:cd08844   95 PQANDCDVLKEQWIRAKY 112
ArfGap_ARAP2 cd08856
ArfGap with Rho-Gap domain, ANK repeat and PH domain-containing protein 2; The ARAP subfamily ...
587-684 2.16e-23

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: 96.13  E-value: 2.16e-23
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564359681 587 NSTCVDCGAPNPTWASLNLGALICIECSGIHRNLGTHLSRVRSLDLDD--WPRELTLVLTAIGNDTANRVWESDTRGRAK 664
Cdd:cd08856   18 NRSCADCKAPDPDWASINLCVVICKKCAGQHRSLGPKDSKVRSLKMDAsiWSNELIELFIVVGNKPANLFWAANLFSEED 97
                         90       100
                 ....*....|....*....|
gi 564359681 665 PTRDSSREERESWIRAKYEQ 684
Cdd:cd08856   98 LHMDSDVEQRTPFITQKYKE 117
ArfGap_ARAP3 cd17902
ArfGap with Rho-Gap domain, ANK repeat and PH domain-containing protein 3; The ARAP subfamily ...
579-687 1.49e-22

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: 93.43  E-value: 1.49e-22
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564359681 579 QAIRNAKGNSTCVDCGAPNPTWASLNLGALICIECSGIHRNLGTHLSRVRSLDLDD--WPRELTLVLTAIGNDTANRVWE 656
Cdd:cd17902    5 EKIWSNKANRFCADCHASSPDWASINLCVVICKQCAGQHRSLGSGISKVQSLKLDTsvWSNEIVQLFIVLGNDRANRFWA 84
                         90       100       110
                 ....*....|....*....|....*....|.
gi 564359681 657 SDTRGRAKPTRDSSREERESWIRAKYEQLLF 687
Cdd:cd17902   85 ARLPASEALHPDATPEQRREFISRKYREGRF 115
ArfGap_GIT2 cd08847
GIT2 GTPase activating protein for Arf; The GIT (G-protein coupled receptor kinase-interacting ...
585-682 1.63e-22

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: 93.16  E-value: 1.63e-22
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564359681 585 KGNSTCVDCGAPNPTWASLNLGALICIECSGIHRNLGTHLSRVRSLDLDDWPRELTLVLTAIGNDTANRVWE-------S 657
Cdd:cd08847    6 RSSEVCADCSTSDPRWASVNRGVLICDECCSVHRSLGRHISQVRHLKHTSWPPTLLQMVQTLYNNGANSIWEhslldpaS 85
                         90       100
                 ....*....|....*....|....*.
gi 564359681 658 DTRGRAKPT-RDSSREERESWIRAKY 682
Cdd:cd08847   86 IMSGKRKANpQDKVHPNKAEFIRAKY 111
ArfGap_AGFG cd08838
ArfGAP domain of the AGFG subfamily (ArfGAP domain and FG repeat-containing proteins); The ...
586-684 8.82e-19

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


Pssm-ID: 350067 [Multi-domain]  Cd Length: 113  Bit Score: 82.63  E-value: 8.82e-19
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564359681 586 GNSTCVDCGAPNPTWASLNLGALICIECSGIHRNLGtHlsRVRSLDLDDWPRELTLVLTAIGNDTANRVWESDTRGRAKP 665
Cdd:cd08838   12 ENKRCFDCGQRGPTYVNLTFGTFVCTTCSGIHREFN-H--RVKSISMSTFTPEEVEFLQAGGNEVARKIWLAKWDPRTDP 88
                         90       100
                 ....*....|....*....|
gi 564359681 666 TRDSSREER-ESWIRAKYEQ 684
Cdd:cd08838   89 EPDSGDDQKiREFIRLKYVD 108
ArfGap_ArfGap2 cd09029
Arf1 GTPase-activating protein 2; ArfGAP (ADP Ribosylation Factor GTPase Activating Protein) ...
581-635 1.66e-18

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: 82.03  E-value: 1.66e-18
                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|....*.
gi 564359681 581 IRNAKGNSTCVDCGAPNPTWASLNLGALICIECSGIHRNLGTHLSRVRSLDLD-DW 635
Cdd:cd09029   13 LRAIPTNKACFDCGAKNPSWASITYGVFLCIDCSGVHRSLGVHLSFIRSTELDsNW 68
ArfGap_ArfGap3 cd09028
Arf1 GTPase-activating protein 3; ArfGAP (ADP Ribosylation Factor GTPase Activating Protein) ...
572-635 3.53e-18

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: 81.27  E-value: 3.53e-18
                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 564359681 572 QSEAVAIQAIRNAKGNSTCVDCGAPNPTWASLNLGALICIECSGIHRNLGTHLSRVRSLDLD-DW 635
Cdd:cd09028    4 QDIAAIFKRLRSVPTNKVCFDCGAKNPSWASITYGVFLCIDCSGIHRSLGVHLSFIRSTELDsNW 68
Ras cd00876
Rat sarcoma (Ras) family of small guanosine triphosphatases (GTPases); The Ras family of the ...
72-230 4.57e-18

Rat sarcoma (Ras) family of small guanosine triphosphatases (GTPases); The Ras family of the Ras superfamily includes classical N-Ras, H-Ras, and K-Ras, as well as R-Ras, Rap, Ral, Rheb, Rhes, ARHI, RERG, Rin/Rit, RSR1, RRP22, Ras2, Ras-dva, and RGK proteins. Ras proteins regulate cell growth, proliferation and differentiation. Ras is activated by guanine nucleotide exchange factors (GEFs) that release GDP and allow GTP binding. Many RasGEFs have been identified. These are sequestered in the cytosol until activation by growth factors triggers recruitment to the plasma membrane or Golgi, where the GEF colocalizes with Ras. Active GTP-bound Ras interacts with several effector proteins: among the best characterized are the Raf kinases, phosphatidylinositol 3-kinase (PI3K), RalGEFs and NORE/MST1. Most Ras proteins contain a lipid modification site at the C-terminus, with a typical sequence motif CaaX, where a = an aliphatic amino acid and X = any amino acid. Lipid binding is essential for membrane attachment, a key feature of most Ras proteins. Due to the presence of truncated sequences in this CD, the lipid modification site is not available for annotation.


Pssm-ID: 206642 [Multi-domain]  Cd Length: 160  Bit Score: 82.19  E-value: 4.57e-18
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564359681  72 RLGVLGDVRSGKSSLIHRFLTGSYQVLEKPESEQ-YKKEMLVDGQT-HLVLI----REEAGAPDAKFSGWADAVIFVFSL 145
Cdd:cd00876    1 KLVVLGAGGVGKSALTIRFVSGEFVEEYDPTIEDsYRKQIVVDGETyTLDILdtagQEEFSAMRDQYIRNGDGFILVYSI 80
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564359681 146 EDESSFQAVSHLHGQLISLRGEGRggLALALVGtqDRISASSPRVVGDARARALcTDMKRCSYYETCATYGLNVDRVFQE 225
Cdd:cd00876   81 TSRESFEEIKNIREQILRVKDKED--VPIVLVG--NKCDLENERQVSTEEGEAL-AEEWGCPFLETSAKTNINIDELFNT 155

                 ....*
gi 564359681 226 VAQKV 230
Cdd:cd00876  156 LVREI 160
ArfGap_GIT1 cd08846
GIT1 GTPase activating protein for Arf; The GIT (G-protein coupled receptor kinase-interacting ...
582-682 1.18e-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: 79.38  E-value: 1.18e-17
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564359681 582 RNAKGNSTCVDCGAPNPTWASLNLGALICIECSGIHRNLGTHLSRVRSLDLDDWPRELTLVLTAIGNDTANRVWE----- 656
Cdd:cd08846    3 RKGPRAEVCADCSAPDPGWASINRGVLICDECCSVHRSLGRHISIVKHLRHSAWPPTLLQMVHTLASNGANSIWEhslld 82
                         90       100       110
                 ....*....|....*....|....*....|
gi 564359681 657 ----SDTRGRAKPtRDSSREERESWIRAKY 682
Cdd:cd08846   83 paqvQSGRRKANP-QDKVHPTKSEFIRAKY 111
PLN03114 PLN03114
ADP-ribosylation factor GTPase-activating protein AGD10; Provisional
587-699 3.78e-15

ADP-ribosylation factor GTPase-activating protein AGD10; Provisional


Pssm-ID: 178661 [Multi-domain]  Cd Length: 395  Bit Score: 78.36  E-value: 3.78e-15
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564359681 587 NSTCVDCGAPNPTWASLNLGALICIECSGIHRNLGTHLSRVRSLDLDDWPRELTLVLTAIGNDTANRV-----WESDTRG 661
Cdd:PLN03114  22 NKICFDCNAKNPTWASVTYGIFLCIDCSAVHRSLGVHISFVRSTNLDSWSSEQLKMMIYGGNNRAQVFfkqygWSDGGKT 101
                         90       100       110       120
                 ....*....|....*....|....*....|....*....|....
gi 564359681 662 RAKPTRDSSREERE----SWIRAKYEQLLFL--APLGTTEEPLG 699
Cdd:PLN03114 102 EAKYTSRAADLYKQilakEVAKSKAEEELDLppSPPDSTQVPNG 145
Rap_like cd04136
Rap-like family consists of Rap1, Rap2 and RSR1; The Rap subfamily consists of the Rap1, Rap2, ...
70-230 6.54e-14

Rap-like family consists of Rap1, Rap2 and RSR1; The Rap subfamily consists of the Rap1, Rap2, and RSR1. Rap subfamily proteins perform different cellular functions, depending on the isoform and its subcellular localization. For example, in rat salivary gland, neutrophils, and platelets, Rap1 localizes to secretory granules and is believed to regulate exocytosis or the formation of secretory granules. Rap1 has also been shown to localize in the Golgi of rat fibroblasts, zymogen granules, plasma membrane, and microsomal membrane of the pancreatic acini, as well as in the endocytic compartment of skeletal muscle cells and fibroblasts. Rap1 localizes in the nucleus of human oropharyngeal squamous cell carcinomas (SCCs) and cell lines. Rap1 plays a role in phagocytosis by controlling the binding of adhesion receptors (typically integrins) to their ligands. In yeast, Rap1 has been implicated in multiple functions, including activation and silencing of transcription and maintenance of telomeres. Rap2 is involved in multiple functions, including activation of c-Jun N-terminal kinase (JNK) to regulate the actin cytoskeleton and activation of the Wnt/beta-catenin signaling pathway in embryonic Xenopus. A number of effector proteins for Rap2 have been identified, including isoform 3 of the human mitogen-activated protein kinase kinase kinase kinase 4 (MAP4K4) and Traf2- and Nck-interacting kinase (TNIK), and the RalGEFs RalGDS, RGL, and Rlf, which also interact with Rap1 and Ras. RSR1 is the fungal homolog of Rap1 and Rap2. In budding yeasts, it is involved in selecting a site for bud growth, which directs the establishment of cell polarization. The Rho family GTPase Cdc42 and its GEF, Cdc24, then establish an axis of polarized growth. It is believed that Cdc42 interacts directly with RSR1 in vivo. In filamentous fungi such as Ashbya gossypii, RSR1 is a key regulator of polar growth in the hypha. Most Ras proteins contain a lipid modification site at the C-terminus, with a typical sequence motif CaaX, where a = an aliphatic amino acid and X = any amino acid. Lipid binding is essential for membrane attachment, a key feature of most Ras proteins. Due to the presence of truncated sequences in this CD, the lipid modification site is not available for annotation.


Pssm-ID: 206708 [Multi-domain]  Cd Length: 164  Bit Score: 70.28  E-value: 6.54e-14
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564359681  70 ELRLGVLGDVRSGKSSLIHRFLTGSYQVLEKPESEQ-YKKEMLVDGQTHLVLIREEAGApdAKFSGWAD-------AVIF 141
Cdd:cd04136    1 EYKLVVLGSGGVGKSALTVQFVQGIFVDKYDPTIEDsYRKQIEVDCQQCMLEILDTAGT--EQFTAMRDlyikngqGFAL 78
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564359681 142 VFSLEDESSFQAVSHLHGQLISLRGEGRggLALALVGtqDRISASSPRVVGDARARALCTDMKRCSYYETCATYGLNVDR 221
Cdd:cd04136   79 VYSITAQQSFNDLQDLREQILRVKDTED--VPMILVG--NKCDLEDERVVSKEEGQNLARQWGNCPFLETSAKSKINVDE 154

                 ....*....
gi 564359681 222 VFQEVAQKV 230
Cdd:cd04136  155 IFYDLVRQI 163
RERG_RasL11_like cd04146
Ras-related and Estrogen-Regulated Growth inhibitor (RERG) and Ras-like 11 (RasL11)-like ...
73-230 1.43e-13

Ras-related and Estrogen-Regulated Growth inhibitor (RERG) and Ras-like 11 (RasL11)-like families; RERG (Ras-related and Estrogen- Regulated Growth inhibitor) and Ras-like 11 are members of a novel subfamily of Ras that were identified based on their behavior in breast and prostate tumors, respectively. RERG expression was decreased or lost in a significant fraction of primary human breast tumors that lack estrogen receptor and are correlated with poor clinical prognosis. Elevated RERG expression correlated with favorable patient outcome in a breast tumor subtype that is positive for estrogen receptor expression. In contrast to most Ras proteins, RERG overexpression inhibited the growth of breast tumor cells in vitro and in vivo. RasL11 was found to be ubiquitously expressed in human tissue, but down-regulated in prostate tumors. Both RERG and RasL11 lack the C-terminal CaaX prenylation motif, where a = an aliphatic amino acid and X = any amino acid, and are localized primarily in the cytoplasm. Both are believed to have tumor suppressor activity.


Pssm-ID: 206713 [Multi-domain]  Cd Length: 166  Bit Score: 69.23  E-value: 1.43e-13
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564359681  73 LGVLGDVRSGKSSLIHRFLT----GSYqvlEKPESEQYKKEMLVDGQTHLVLIREEAG--APDAKFS-----GWADAVIF 141
Cdd:cd04146    2 IAVLGASGVGKSALTVRFLTkrfiGEY---EPNLESLYSRQVTIDGEQVSLEIQDTPGqqQNEDPESlerslRWADGFVL 78
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564359681 142 VFSLEDESSFQAVSHLHgQLISLRGEGRGGLALALVGT-QDRISAsspRVVGDARARALCTDMkRCSYYE--TCATYgLN 218
Cdd:cd04146   79 VYSITDRSSFDVVSQLL-QLIREIKKRDGEIPVILVGNkADLLHS---RQVSTEEGQKLALEL-GCLFFEvsAAENY-LE 152
                        170
                 ....*....|..
gi 564359681 219 VDRVFQEVAQKV 230
Cdd:cd04146  153 VQNVFHELCREV 164
small_GTPase smart00010
Small GTPase of the Ras superfamily; ill-defined subfamily; SMART predicts Ras-like small ...
69-236 5.99e-13

Small GTPase of the Ras superfamily; ill-defined subfamily; SMART predicts Ras-like small GTPases of the ARF, RAB, RAN, RAS, and SAR subfamilies. Others that could not be classified in this way are predicted to be members of the small GTPase superfamily without predictions of the subfamily.


Pssm-ID: 197466 [Multi-domain]  Cd Length: 166  Bit Score: 67.59  E-value: 5.99e-13
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564359681    69 PELRLGVLGDVRSGKSSLIHRFLTGSYqvLEK--PESE-QYKKEMLVDGQTHLVLIREEAGapDAKFSGWAD-------A 138
Cdd:smart00010   1 REYKLVVLGGGGVGKSALTIQFVQGHF--VDEydPTIEdSYRKQIEIDGEVCLLDILDTAG--QEEFSAMRDqymrtgeG 76
                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564359681   139 VIFVFSLEDESSFQAVSHLHGQLisLRGEGRGGLALALVGTQ-DRISAsspRVVGDARARALCTDMKrCSYYETCATYGL 217
Cdd:smart00010  77 FLLVYSITDRQSFEEIAKFREQI--LRVKDRDDVPIVLVGNKcDLENE---RVVSTEEGKELARQWG-CPFLETSAKERI 150
                          170
                   ....*....|....*....
gi 564359681   218 NVDRVFQEVaqkVVTLRKQ 236
Cdd:smart00010 151 NVDEAFYDL---VREIRKS 166
Ras pfam00071
Ras family; Includes sub-families Ras, Rab, Rac, Ral, Ran, Rap Ypt1 and more. Shares P-loop ...
75-230 9.40e-13

Ras family; Includes sub-families Ras, Rab, Rac, Ral, Ran, Rap Ypt1 and more. Shares P-loop motif with GTP_EFTU, arf and myosin_head. See pfam00009 pfam00025, pfam00063. As regards Rab GTPases, these are important regulators of vesicle formation, motility and fusion. They share a fold in common with all Ras GTPases: this is a six-stranded beta-sheet surrounded by five alpha-helices.


Pssm-ID: 425451 [Multi-domain]  Cd Length: 162  Bit Score: 66.77  E-value: 9.40e-13
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564359681   75 VLGDVRSGKSSLIHRFLTGSYQvlEKPES----EQYKKEMLVDGQTHLVLIREEAGA------PDAKFSGwADAVIFVFS 144
Cdd:pfam00071   4 LVGDGGVGKSSLLIRFTQNKFP--EEYIPtigvDFYTKTIEVDGKTVKLQIWDTAGQerfralRPLYYRG-ADGFLLVYD 80
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564359681  145 LEDESSFQAVSHLHGQLISLRGEgrgGLALALVGTQdrISASSPRVVGDARARALCTDMKrCSYYETCATYGLNVDRVFQ 224
Cdd:pfam00071  81 ITSRDSFENVKKWVEEILRHADE---NVPIVLVGNK--CDLEDQRVVSTEEGEALAKELG-LPFMETSAKTNENVEEAFE 154

                  ....*.
gi 564359681  225 EVAQKV 230
Cdd:pfam00071 155 ELAREI 160
Rab cd00154
Ras-related in brain (Rab) family of small guanosine triphosphatases (GTPases); Rab GTPases ...
71-228 9.78e-13

Ras-related in brain (Rab) family of small guanosine triphosphatases (GTPases); Rab GTPases form the largest family within the Ras superfamily. There are at least 60 Rab genes in the human genome, and a number of Rab GTPases are conserved from yeast to humans. Rab GTPases are small, monomeric proteins that function as molecular switches to regulate vesicle trafficking pathways. The different Rab GTPases are localized to the cytosolic face of specific intracellular membranes, where they regulate distinct steps in membrane traffic pathways. In the GTP-bound form, Rab GTPases recruit specific sets of effector proteins onto membranes. Through their effectors, Rab GTPases regulate vesicle formation, actin- and tubulin-dependent vesicle movement, and membrane fusion. GTPase activating proteins (GAPs) interact with GTP-bound Rab and accelerate the hydrolysis of GTP to GDP. Guanine nucleotide exchange factors (GEFs) interact with GDP-bound Rabs to promote the formation of the GTP-bound state. Rabs are further regulated by guanine nucleotide dissociation inhibitors (GDIs), which mask C-terminal lipid binding and promote cytosolic localization. While most unicellular organisms possess 5-20 Rab members, several have been found to possess 60 or more Rabs; for many of these Rab isoforms, homologous proteins are not found in other organisms. Most Rab GTPases contain a lipid modification site at the C-terminus, with sequence motifs CC, CXC, or CCX. Lipid binding is essential for membrane attachment, a key feature of most Rab proteins. Since crystal structures often lack C-terminal residues, the lipid modification site is not available for annotation in many of the CDs in the hierarchy, but is included where possible.


Pssm-ID: 206640 [Multi-domain]  Cd Length: 159  Bit Score: 66.71  E-value: 9.78e-13
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564359681  71 LRLGVLGDVRSGKSSLIHRFLTGSYQvlEKPES----EQYKKEMLVDGQTHLVLIREEAGapDAKFS--------GwADA 138
Cdd:cd00154    1 FKIVLIGDSGVGKTSLLLRFVDNKFS--ENYKStigvDFKSKTIEVDGKKVKLQIWDTAG--QERFRsitssyyrG-AHG 75
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564359681 139 VIFVFSLEDESSFQAVSHLHGQLISlrgEGRGGLALALVGTqdRISASSPRVVGDARARALCTDMKrCSYYETCATYGLN 218
Cdd:cd00154   76 AILVYDVTNRESFENLDKWLNELKE---YAPPNIPIILVGN--KSDLEDERQVSTEEAQQFAKENG-LLFFETSAKTGEN 149
                        170
                 ....*....|
gi 564359681 219 VDRVFQEVAQ 228
Cdd:cd00154  150 VDEAFESLAR 159
Ras_like_GTPase cd00882
Rat sarcoma (Ras)-like superfamily of small guanosine triphosphatases (GTPases); Ras-like ...
74-228 1.29e-12

Rat sarcoma (Ras)-like superfamily of small guanosine triphosphatases (GTPases); Ras-like GTPase superfamily. The Ras-like superfamily of small GTPases consists of several families with an extremely high degree of structural and functional similarity. The Ras superfamily is divided into at least four families in eukaryotes: the Ras, Rho, Rab, and Sar1/Arf families. This superfamily also includes proteins like the GTP translation factors, Era-like GTPases, and G-alpha chain of the heterotrimeric G proteins. Members of the Ras superfamily regulate a wide variety of cellular functions: the Ras family regulates gene expression, the Rho family regulates cytoskeletal reorganization and gene expression, the Rab and Sar1/Arf families regulate vesicle trafficking, and the Ran family regulates nucleocytoplasmic transport and microtubule organization. The GTP translation factor family regulates initiation, elongation, termination, and release in translation, and the Era-like GTPase family regulates cell division, sporulation, and DNA replication. Members of the Ras superfamily are identified by the GTP binding site, which is made up of five characteristic sequence motifs, and the switch I and switch II regions.


Pssm-ID: 206648 [Multi-domain]  Cd Length: 161  Bit Score: 66.33  E-value: 1.29e-12
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564359681  74 GVLGDVRSGKSSLIHRFLTGSYQVLEKPES---EQYKKEMLVDGQTHLVLIREEAGAPDAKFSG----------WADAVI 140
Cdd:cd00882    1 VVVGRGGVGKSSLLNALLGGEVGEVSDVPGttrDPDVYVKELDKGKVKLVLVDTPGLDEFGGLGreelarlllrGADLIL 80
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564359681 141 FVFSLEDESSFQAVshlhgQLISLRGEGRGGLALALVGTQ-DRISASSPRVVGDARARALctdMKRCSYYETCATYGLNV 219
Cdd:cd00882   81 LVVDSTDRESEEDA-----KLLILRRLRKEGIPIILVGNKiDLLEEREVEELLRLEELAK---ILGVPVFEVSAKTGEGV 152

                 ....*....
gi 564359681 220 DRVFQEVAQ 228
Cdd:cd00882  153 DELFEKLIE 161
RAS smart00173
Ras subfamily of RAS small GTPases; Similar in fold and function to the bacterial EF-Tu GTPase. ...
72-226 1.65e-12

Ras subfamily of RAS small GTPases; Similar in fold and function to the bacterial EF-Tu GTPase. p21Ras couples receptor Tyr kinases and G protein receptors to protein kinase cascades


Pssm-ID: 214541 [Multi-domain]  Cd Length: 164  Bit Score: 66.04  E-value: 1.65e-12
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564359681    72 RLGVLGDVRSGKSSLIHRFLTGSYQVLEKPESE-QYKKEMLVDGQTHLVLIREEAGapDAKFSGWAD-------AVIFVF 143
Cdd:smart00173   2 KLVVLGSGGVGKSALTIQFIQGHFVDDYDPTIEdSYRKQIEIDGEVCLLDILDTAG--QEEFSAMRDqymrtgeGFLLVY 79
                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564359681   144 SLEDESSFQAVSHLHGQLisLRGEGRGGLALALVGTQ-DRISAsspRVVGDARARALCTDMKrCSYYETCATYGLNVDRV 222
Cdd:smart00173  80 SITDRQSFEEIKKFREQI--LRVKDRDDVPIVLVGNKcDLESE---RVVSTEEGKELARQWG-CPFLETSAKERVNVDEA 153

                   ....
gi 564359681   223 FQEV 226
Cdd:smart00173 154 FYDL 157
Rab7 cd01862
Rab GTPase family 7 (Rab7); Rab7 subfamily. Rab7 is a small Rab GTPase that regulates ...
71-236 2.84e-12

Rab GTPase family 7 (Rab7); Rab7 subfamily. Rab7 is a small Rab GTPase that regulates vesicular traffic from early to late endosomal stages of the endocytic pathway. The yeast Ypt7 and mammalian Rab7 are both involved in transport to the vacuole/lysosome, whereas Ypt7 is also required for homotypic vacuole fusion. Mammalian Rab7 is an essential participant in the autophagic pathway for sequestration and targeting of cytoplasmic components to the lytic compartment. Mammalian Rab7 is also proposed to function as a tumor suppressor. GTPase activating proteins (GAPs) interact with GTP-bound Rab and accelerate the hydrolysis of GTP to GDP. Guanine nucleotide exchange factors (GEFs) interact with GDP-bound Rabs to promote the formation of the GTP-bound state. Rabs are further regulated by guanine nucleotide dissociation inhibitors (GDIs), which facilitate Rab recycling by masking C-terminal lipid binding and promoting cytosolic localization. Most Rab GTPases contain a lipid modification site at the C-terminus, with sequence motifs CC, CXC, or CCX. Lipid binding is essential for membrane attachment, a key feature of most Rab proteins. Due to the presence of truncated sequences in this CD, the lipid modification site is not available for annotation.


Pssm-ID: 206655 [Multi-domain]  Cd Length: 172  Bit Score: 65.76  E-value: 2.84e-12
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564359681  71 LRLGVLGDVRSGKSSLIHRFLTGSYqvlekpeSEQYK---------KEMLVDGQTHLVLIREEAGAPD------AKFSGw 135
Cdd:cd01862    1 LKVIILGDSGVGKTSLMNQYVNKKF-------SNQYKatigadfltKEVTVDDRLVTLQIWDTAGQERfqslgvAFYRG- 72
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564359681 136 ADAVIFVFSLEDESSFQAVSHLHGQ-LISLRGEGRGGLALALVGtqDRISASSPRVVGDARARALCTDMKRCSYYETCAT 214
Cdd:cd01862   73 ADCCVLVYDVTNPKSFESLDSWRDEfLIQASPRDPENFPFVVLG--NKIDLEEKRQVSTKKAQQWCKSKGNIPYFETSAK 150
                        170       180
                 ....*....|....*....|..
gi 564359681 215 YGLNVDRVFQEVAQKVVTLRKQ 236
Cdd:cd01862  151 EAINVDQAFETIARLALEQEKE 172
Rap2 cd04176
Rap2 family GTPase consists of Rap2a, Rap2b, and Rap2c; The Rap2 subgroup is part of the Rap ...
70-230 6.15e-12

Rap2 family GTPase consists of Rap2a, Rap2b, and Rap2c; The Rap2 subgroup is part of the Rap subfamily of the Ras family. It consists of Rap2a, Rap2b, and Rap2c. Both isoform 3 of the human mitogen-activated protein kinase kinase kinase kinase 4 (MAP4K4) and Traf2- and Nck-interacting kinase (TNIK) are putative effectors of Rap2 in mediating the activation of c-Jun N-terminal kinase (JNK) to regulate the actin cytoskeleton. In human platelets, Rap2 was shown to interact with the cytoskeleton by binding the actin filaments. In embryonic Xenopus development, Rap2 is necessary for the Wnt/beta-catenin signaling pathway. The Rap2 interacting protein 9 (RPIP9) is highly expressed in human breast carcinomas and correlates with a poor prognosis, suggesting a role for Rap2 in breast cancer oncogenesis. Rap2b, but not Rap2a, Rap2c, Rap1a, or Rap1b, is expressed in human red blood cells, where it is believed to be involved in vesiculation. A number of additional effector proteins for Rap2 have been identified, including the RalGEFs RalGDS, RGL, and Rlf, which also interact with Rap1 and Ras. Most Ras proteins contain a lipid modification site at the C-terminus, with a typical sequence motif CaaX, where a = an aliphatic amino acid and X = any amino acid. Lipid binding is essential for membrane attachment, a key feature of most Ras proteins. Due to the presence of truncated sequences in this CD, the lipid modification site is not available for annotation.


Pssm-ID: 133376 [Multi-domain]  Cd Length: 163  Bit Score: 64.47  E-value: 6.15e-12
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564359681  70 ELRLGVLGDVRSGKSSLIHRFLTGSYqvLEK--PESEQ-YKKEMLVDGQTHLVLIREEAGApdAKFSGWAD-------AV 139
Cdd:cd04176    1 EYKVVVLGSGGVGKSALTVQFVSGTF--IEKydPTIEDfYRKEIEVDSSPSVLEILDTAGT--EQFASMRDlyikngqGF 76
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564359681 140 IFVFSLEDESSFQAVSHLHGQLIslRGEGRGGLALALVGtqDRISASSPRVVGDARARALCTDMKrCSYYETCATYGLNV 219
Cdd:cd04176   77 IVVYSLVNQQTFQDIKPMRDQIV--RVKGYEKVPIILVG--NKVDLESEREVSSAEGRALAEEWG-CPFMETSAKSKTMV 151
                        170
                 ....*....|.
gi 564359681 220 DRVFQEVAQKV 230
Cdd:cd04176  152 NELFAEIVRQM 162
RAB smart00175
Rab subfamily of small GTPases; Rab GTPases are implicated in vesicle trafficking.
71-231 1.40e-11

Rab subfamily of small GTPases; Rab GTPases are implicated in vesicle trafficking.


Pssm-ID: 197555 [Multi-domain]  Cd Length: 164  Bit Score: 63.68  E-value: 1.40e-11
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564359681    71 LRLGVLGDVRSGKSSLIHRFLTGSYqvlekpeSEQYK---------KEMLVDGQTHLVLIREEAGAP------DAKFSGw 135
Cdd:smart00175   1 FKIILIGDSGVGKSSLLSRFTDGKF-------SEQYKstigvdfktKTIEVDGKRVKLQIWDTAGQErfrsitSSYYRG- 72
                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564359681   136 ADAVIFVFSLEDESSFQAVSHLHGQLISLRGEgrgGLALALVGTqdRISASSPRVVGDARARALCTDmKRCSYYETCATY 215
Cdd:smart00175  73 AVGALLVYDITNRESFENLENWLKELREYASP---NVVIMLVGN--KSDLEEQRQVSREEAEAFAEE-HGLPFFETSAKT 146
                          170
                   ....*....|....*.
gi 564359681   216 GLNVDRVFQEVAQKVV 231
Cdd:smart00175 147 NTNVEEAFEELAREIL 162
RSR1 cd04177
RSR1/Bud1p family GTPase; RSR1/Bud1p is a member of the Rap subfamily of the Ras family that ...
70-231 1.12e-10

RSR1/Bud1p family GTPase; RSR1/Bud1p is a member of the Rap subfamily of the Ras family that is found in fungi. In budding yeasts, RSR1 is involved in selecting a site for bud growth on the cell cortex, which directs the establishment of cell polarization. The Rho family GTPase cdc42 and its GEF, cdc24, then establish an axis of polarized growth by organizing the actin cytoskeleton and secretory apparatus at the bud site. It is believed that cdc42 interacts directly with RSR1 in vivo. In filamentous fungi, polar growth occurs at the tips of hypha and at novel growth sites along the extending hypha. In Ashbya gossypii, RSR1 is a key regulator of hyphal growth, localizing at the tip region and regulating in apical polarization of the actin cytoskeleton. Most Ras proteins contain a lipid modification site at the C-terminus, with a typical sequence motif CaaX, where a = an aliphatic amino acid and X = any amino acid. Lipid binding is essential for membrane attachment, a key feature of most Ras proteins.


Pssm-ID: 133377 [Multi-domain]  Cd Length: 168  Bit Score: 60.96  E-value: 1.12e-10
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564359681  70 ELRLGVLGDVRSGKSSLIHRFLTGSYQVLEKPESE-QYKKEMLVDGQTHLVLIREEAGApdAKFSGWADAVI-------F 141
Cdd:cd04177    1 DYKIVVLGAGGVGKSALTVQFVQNVFIESYDPTIEdSYRKQVEIDGRQCDLEILDTAGT--EQFTAMRELYIksgqgflL 78
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564359681 142 VFSLEDESSFQAVSHLHGQLISLRGEGRggLALALVGTQDRISASspRVVGDARARALCTDMKRCSYYETCATYGLNVDR 221
Cdd:cd04177   79 VYSVTSEASLNELGELREQVLRIKDSDN--VPMVLVGNKADLEDD--RQVSREDGVSLSQQWGNVPFYETSARKRTNVDE 154
                        170
                 ....*....|
gi 564359681 222 VFQEVAQKVV 231
Cdd:cd04177  155 VFIDLVRQII 164
M_R_Ras_like cd04145
R-Ras2/TC21, M-Ras/R-Ras3; The M-Ras/R-Ras-like subfamily contains R-Ras2/TC21, M-Ras/R-Ras3, ...
69-230 1.38e-10

R-Ras2/TC21, M-Ras/R-Ras3; The M-Ras/R-Ras-like subfamily contains R-Ras2/TC21, M-Ras/R-Ras3, and related members of the Ras family. M-Ras is expressed in lympho-hematopoetic cells. It interacts with some of the known Ras effectors, but appears to also have its own effectors. Expression of mutated M-Ras leads to transformation of several types of cell lines, including hematopoietic cells, mammary epithelial cells, and fibroblasts. Overexpression of M-Ras is observed in carcinomas from breast, uterus, thyroid, stomach, colon, kidney, lung, and rectum. In addition, expression of a constitutively active M-Ras mutant in murine bone marrow induces a malignant mast cell leukemia that is distinct from the monocytic leukemia induced by H-Ras. TC21, along with H-Ras, has been shown to regulate the branching morphogenesis of ureteric bud cell branching in mice. Most Ras proteins contain a lipid modification site at the C-terminus, with a typical sequence motif CaaX, where a = an aliphatic amino acid and X = any amino acid. Lipid binding is essential for membrane attachment, a key feature of most Ras proteins. Due to the presence of truncated sequences in this CD, the lipid modification site is not available for annotation.


Pssm-ID: 133345 [Multi-domain]  Cd Length: 164  Bit Score: 60.50  E-value: 1.38e-10
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564359681  69 PELRLGVLGDVRSGKSSLIHRFLTgSYQVLE-KPESE-QYKKEMLVDGQ-THLVLI----REEAGAPDAKFSGWADAVIF 141
Cdd:cd04145    1 PTYKLVVVGGGGVGKSALTIQFIQ-SYFVTDyDPTIEdSYTKQCEIDGQwARLDILdtagQEEFSAMREQYMRTGEGFLL 79
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564359681 142 VFSLEDESSFQAVSHLHGQLisLRGEGRGGLALALVGtqDRISASSPRVVGDARARALCTDMKrCSYYETCATYGLNVDR 221
Cdd:cd04145   80 VFSVTDRGSFEEVDKFHTQI--LRVKDRDEFPMILVG--NKADLEHQRQVSREEGQELARQLK-IPYIETSAKDRVNVDK 154

                 ....*....
gi 564359681 222 VFQEVAQKV 230
Cdd:cd04145  155 AFHDLVRVI 163
Ras2 cd04144
Rat sarcoma (Ras) family 2 of small guanosine triphosphatases (GTPases); The Ras2 subfamily, ...
72-238 2.82e-10

Rat sarcoma (Ras) family 2 of small guanosine triphosphatases (GTPases); The Ras2 subfamily, found exclusively in fungi, was first identified in Ustilago maydis. In U. maydis, Ras2 is regulated by Sql2, a protein that is homologous to GEFs (guanine nucleotide exchange factors) of the CDC25 family. Ras2 has been shown to induce filamentous growth, but the signaling cascade through which Ras2 and Sql2 regulate cell morphology is not known. Most Ras proteins contain a lipid modification site at the C-terminus, with a typical sequence motif CaaX, where a = an aliphatic amino acid and X = any amino acid. Lipid binding is essential for membrane attachment, a key feature of most Ras proteins.


Pssm-ID: 133344 [Multi-domain]  Cd Length: 190  Bit Score: 60.25  E-value: 2.82e-10
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564359681  72 RLGVLGDVRSGKSSLIHRFLTGSYQVLEKPESEQ-YKKEMLVDGQTHLVLIREEAGAPD--AKFSGW---ADAVIFVFSL 145
Cdd:cd04144    1 KLVVLGDGGVGKTALTIQLCLNHFVETYDPTIEDsYRKQVVVDGQPCMLEVLDTAGQEEytALRDQWireGEGFILVYSI 80
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564359681 146 EDESSFQAVSHLHGQLISLRGEGRGGLALALVGTQ-DRISAsspRVVGDARARALCTDMKrCSYYETCATYGLNVDRVFQ 224
Cdd:cd04144   81 TSRSTFERVERFREQIQRVKDESAADVPIMIVGNKcDKVYE---REVSTEEGAALARRLG-CEFIEASAKTNVNVERAFY 156
                        170
                 ....*....|....
gi 564359681 225 EVAQKvvtLRKQQQ 238
Cdd:cd04144  157 TLVRA---LRQQRQ 167
Rab9 cd04116
Rab GTPase family 9 (Rab9); Rab9 is found in late endosomes, together with mannose 6-phosphate ...
71-230 8.85e-10

Rab GTPase family 9 (Rab9); Rab9 is found in late endosomes, together with mannose 6-phosphate receptors (MPRs) and the tail-interacting protein of 47 kD (TIP47). Rab9 is a key mediator of vesicular transport from late endosomes to the trans-Golgi network (TGN) by redirecting the MPRs. Rab9 has been identified as a key component for the replication of several viruses, including HIV1, Ebola, Marburg, and measles, making it a potential target for inhibiting a variety of viruses. GTPase activating proteins (GAPs) interact with GTP-bound Rab and accelerate the hydrolysis of GTP to GDP. Guanine nucleotide exchange factors (GEFs) interact with GDP-bound Rabs to promote the formation of the GTP-bound state. Rabs are further regulated by guanine nucleotide dissociation inhibitors (GDIs), which facilitate Rab recycling by masking C-terminal lipid binding and promoting cytosolic localization. Most Rab GTPases contain a lipid modification site at the C-terminus, with sequence motifs CC, CXC, or CCX. Lipid binding is essential for membrane attachment, a key feature of most Rab proteins. Due to the presence of truncated sequences in this CD, the lipid modification site is not available for annotation.


Pssm-ID: 206697 [Multi-domain]  Cd Length: 170  Bit Score: 58.35  E-value: 8.85e-10
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564359681  71 LRLGVLGDVRSGKSSLIHRFLTGSY--QVLEKPESEQYKKEMLVDGQTHLVLIREEAGAPDAK-----FSGWADAVIFVF 143
Cdd:cd04116    6 LKVILLGDGGVGKSSLMNRYVTNKFdtQLFHTIGVEFLNKDLEVDGHFVTLQIWDTAGQERFRslrtpFYRGSDCCLLTF 85
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564359681 144 SLEDESSFQAVSHLHGQLISLRG-EGRGGLALALVGTQDRISAsspRVVGDARARALCTDMKRCSYYETCATYGLNVDRV 222
Cdd:cd04116   86 SVDDSQSFQNLSNWKKEFIYYADvKEPESFPFVILGNKIDIPE---RQVSTEEAQAWCRDNGDYPYFETSAKDATNVAAA 162

                 ....*...
gi 564359681 223 FQEVAQKV 230
Cdd:cd04116  163 FEEAVRRV 170
ANKYR COG0666
Ankyrin repeat [Signal transduction mechanisms];
732-791 9.98e-10

Ankyrin repeat [Signal transduction mechanisms];


Pssm-ID: 440430 [Multi-domain]  Cd Length: 289  Bit Score: 60.74  E-value: 9.98e-10
                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|
gi 564359681 732 DPQLRSPLHLAAELAHVVITQLLLWYGADVAARDAQGRTALFYARQAGSQLCADILLQHG 791
Cdd:COG0666  150 DNDGNTPLHLAAANGNLEIVKLLLEAGADVNARDNDGETPLHLAAENGHLEIVKLLLEAG 209
Ras_dva cd04147
Ras - dorsal-ventral anterior localization (Ras-dva) family; Ras-dva subfamily. Ras-dva (Ras - ...
72-230 1.09e-09

Ras - dorsal-ventral anterior localization (Ras-dva) family; Ras-dva subfamily. Ras-dva (Ras - dorsal-ventral anterior localization) subfamily consists of a set of proteins characterized only in Xenopus leavis, to date. In Xenopus Ras-dva expression is activated by the transcription factor Otx2 and begins during gastrulation throughout the anterior ectoderm. Ras-dva expression is inhibited in the anterior neural plate by factor Xanf1. Downregulation of Ras-dva results in head development abnormalities through the inhibition of several regulators of the anterior neural plate and folds patterning, including Otx2, BF-1, Xag2, Pax6, Slug, and Sox9. Downregulation of Ras-dva also interferes with the FGF-8a signaling within the anterior ectoderm. Most Ras proteins contain a lipid modification site at the C-terminus, with a typical sequence motif CaaX, where a = an aliphatic amino acid and X = any amino acid. Lipid binding is essential for membrane attachment, a key feature of most Ras proteins.


Pssm-ID: 206714 [Multi-domain]  Cd Length: 197  Bit Score: 58.70  E-value: 1.09e-09
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564359681  72 RLGVLGDVRSGKSSLIHRFLTGSYQVLEKPESEQ-YKKEMLVDGQTHLVLIREEAGAPD----AKFS-GWADAVIFVFSL 145
Cdd:cd04147    1 RLVFMGAAGVGKTALIQRFLYDTFEPKHRRTVEElHSKEYEVAGVKVTIDILDTSGSYSfpamRKLSiQNGDAFALVYSV 80
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564359681 146 EDESSFQAVSHLHGQLISLRGEGrgglALALVGTQDRISASSPRVVGDARARALCTDMKRCSYYETCATYGLNVDRVFQE 225
Cdd:cd04147   81 DDPESFEEVKRLREEILEVKEDK----FVPIVVVGNKIDSLAERQVEAADALSTVELDWNNGFVEASAKDNENVTEVFKE 156

                 ....*
gi 564359681 226 VAQKV 230
Cdd:cd04147  157 LLQQA 161
ArfGap_AGFG1 cd08857
ArfGAP domain of AGFG1 (ArfGAP domain and FG repeat-containing protein 1); The ArfGAP domain ...
587-684 2.12e-09

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: 55.82  E-value: 2.12e-09
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564359681 587 NSTCVDCGAPNPTWASLNLGALICIECSGIHRNLGTHlSRVRSLDLDDWPRELTLVLTAIGNDTANRVWES--DTRGRAK 664
Cdd:cd08857   14 NRKCFDCDQRGPTYANMTVGSFVCTSCSGILRGLNPP-HRVKSISMTTFTQQEIEFLQKHGNEVCKQIWLGlfDDRSSAI 92
                         90       100
                 ....*....|....*....|
gi 564359681 665 PTRDSSREEREsWIRAKYEQ 684
Cdd:cd08857   93 PDFRDPQKVKE-FLQEKYEK 111
Rab23_like cd04106
Rab GTPase family 23 (Rab23)-like; Rab23-like subfamily. Rab23 is a member of the Rab family ...
75-229 2.16e-09

Rab GTPase family 23 (Rab23)-like; Rab23-like subfamily. Rab23 is a member of the Rab family of small GTPases. In mouse, Rab23 has been shown to function as a negative regulator in the sonic hedgehog (Shh) signaling pathway. Rab23 mediates the activity of Gli2 and Gli3, transcription factors that regulate Shh signaling in the spinal cord, primarily by preventing Gli2 activation in the absence of Shh ligand. Rab23 also regulates a step in the cytoplasmic signal transduction pathway that mediates the effect of Smoothened (one of two integral membrane proteins that are essential components of the Shh signaling pathway in vertebrates). In humans, Rab23 is expressed in the retina. Mice contain an isoform that shares 93% sequence identity with the human Rab23 and an alternative splicing isoform that is specific to the brain. This isoform causes the murine open brain phenotype, indicating it may have a role in the development of the central nervous system. GTPase activating proteins (GAPs) interact with GTP-bound Rab and accelerate the hydrolysis of GTP to GDP. Guanine nucleotide exchange factors (GEFs) interact with GDP-bound Rabs to promote the formation of the GTP-bound state. Rabs are further regulated by guanine nucleotide dissociation inhibitors (GDIs), which facilitate Rab recycling by masking C-terminal lipid binding and promoting cytosolic localization. Most Rab GTPases contain a lipid modification site at the C-terminus, with sequence motifs CC, CXC, or CCX. Lipid binding is essential for membrane attachment, a key feature of most Rab proteins. Due to the presence of truncated sequences in this CD, the lipid modification site is not available for annotation.


Pssm-ID: 133306 [Multi-domain]  Cd Length: 162  Bit Score: 57.07  E-value: 2.16e-09
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564359681  75 VLGDVRSGKSSLIHRFLTGSYqvlekpeSEQYKKEMLVDGQTHLVLIREEagAPDAKFSGW------------------A 136
Cdd:cd04106    5 VVGNGNVGKSSMIQRFVKGIF-------TKDYKKTIGVDFLEKQIFLRQS--DEDVRLMLWdtagqeefdaitkayyrgA 75
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564359681 137 DAVIFVFSLEDESSFQAVSHLHGQLISLRGEgrgglaLALVGTQDRISASSPRVVGDARARALCTDMKrCSYYETCATYG 216
Cdd:cd04106   76 QACILVFSTTDRESFEAIESWKEKVEAECGD------IPMVLVQTKIDLLDQAVITNEEAEALAKRLQ-LPLFRTSVKDD 148
                        170
                 ....*....|...
gi 564359681 217 LNVDRVFQEVAQK 229
Cdd:cd04106  149 FNVTELFEYLAEK 161
Rap1 cd04175
Rap1 family GTPase consists of Rap1a and Rap1b isoforms; The Rap1 subgroup is part of the Rap ...
70-230 2.76e-09

Rap1 family GTPase consists of Rap1a and Rap1b isoforms; The Rap1 subgroup is part of the Rap subfamily of the Ras family. It can be further divided into the Rap1a and Rap1b isoforms. In humans, Rap1a and Rap1b share 95% sequence homology, but are products of two different genes located on chromosomes 1 and 12, respectively. Rap1a is sometimes called smg p21 or Krev1 in the older literature. Rap1 proteins are believed to perform different cellular functions, depending on the isoform, its subcellular localization, and the effector proteins it binds. For example, in rat salivary gland, neutrophils, and platelets, Rap1 localizes to secretory granules and is believed to regulate exocytosis or the formation of secretory granules. Rap1 has also been shown to localize in the Golgi of rat fibroblasts, zymogen granules, plasma membrane, and the microsomal membrane of pancreatic acini, as well as in the endocytic compartment of skeletal muscle cells and fibroblasts. High expression of Rap1 has been observed in the nucleus of human oropharyngeal squamous cell carcinomas (SCCs) and cell lines; interestingly, in the SCCs, the active GTP-bound form localized to the nucleus, while the inactive GDP-bound form localized to the cytoplasm. Rap1 plays a role in phagocytosis by controlling the binding of adhesion receptors (typically integrins) to their ligands. In yeast, Rap1 has been implicated in multiple functions, including activation and silencing of transcription and maintenance of telomeres. Rap1a, which is stimulated by T-cell receptor (TCR) activation, is a positive regulator of T cells by directing integrin activation and augmenting lymphocyte responses. In murine hippocampal neurons, Rap1b determines which neurite will become the axon and directs the recruitment of Cdc42, which is required for formation of dendrites and axons. In murine platelets, Rap1b is required for normal homeostasis in vivo and is involved in integrin activation. Most Ras proteins contain a lipid modification site at the C-terminus, with a typical sequence motif CaaX, where a = an aliphatic amino acid and X = any amino acid. Lipid binding is essential for membrane attachment, a key feature of most Ras proteins. Due to the presence of truncated sequences in this CD, the lipid modification site is not available for annotation.


Pssm-ID: 133375 [Multi-domain]  Cd Length: 164  Bit Score: 56.76  E-value: 2.76e-09
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564359681  70 ELRLGVLGDVRSGKSSLIHRFLTGSYQVLEKPESE-QYKKEMLVDGQTHLVLIREEAGApdAKFSGWAD-------AVIF 141
Cdd:cd04175    1 EYKLVVLGSGGVGKSALTVQFVQGIFVEKYDPTIEdSYRKQVEVDGQQCMLEILDTAGT--EQFTAMRDlymkngqGFVL 78
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564359681 142 VFSLEDESSFQAVSHLHGQLisLRGEGRGGLALALVGtqDRISASSPRVVGDARARALCTDMKrCSYYETCATYGLNVDR 221
Cdd:cd04175   79 VYSITAQSTFNDLQDLREQI--LRVKDTEDVPMILVG--NKCDLEDERVVGKEQGQNLARQWG-CAFLETSAKAKINVNE 153

                 ....*....
gi 564359681 222 VFQEVAQKV 230
Cdd:cd04175  154 IFYDLVRQI 162
ANKYR COG0666
Ankyrin repeat [Signal transduction mechanisms];
732-791 3.60e-09

Ankyrin repeat [Signal transduction mechanisms];


Pssm-ID: 440430 [Multi-domain]  Cd Length: 289  Bit Score: 58.81  E-value: 3.60e-09
                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|
gi 564359681 732 DPQLRSPLHLAAELAHVVITQLLLWYGADVAARDAQGRTALFYARQAGSQLCADILLQHG 791
Cdd:COG0666  117 DKDGETPLHLAAYNGNLEIVKLLLEAGADVNAQDNDGNTPLHLAAANGNLEIVKLLLEAG 176
ANKYR COG0666
Ankyrin repeat [Signal transduction mechanisms];
702-791 5.87e-09

Ankyrin repeat [Signal transduction mechanisms];


Pssm-ID: 440430 [Multi-domain]  Cd Length: 289  Bit Score: 58.04  E-value: 5.87e-09
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564359681 702 LWAAVEAQDVAAVLLLLAHARHGPLDTSVEDPQLRSPLHLAAELAHVVITQLLLWYGADVAARDAQGRTALFYARQAGSQ 781
Cdd:COG0666   54 GALLLLAAALAGDLLVALLLLAAGADINAKDDGGNTLLHAAARNGDLEIVKLLLEAGADVNARDKDGETPLHLAAYNGNL 133
                         90
                 ....*....|
gi 564359681 782 LCADILLQHG 791
Cdd:COG0666  134 EIVKLLLEAG 143
ANKYR COG0666
Ankyrin repeat [Signal transduction mechanisms];
727-791 8.22e-09

Ankyrin repeat [Signal transduction mechanisms];


Pssm-ID: 440430 [Multi-domain]  Cd Length: 289  Bit Score: 57.66  E-value: 8.22e-09
                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 564359681 727 DTSVEDPQLRSPLHLAAELAHVVITQLLLWYGADVAARDAQGRTALFYARQAGSQLCADILLQHG 791
Cdd:COG0666  178 DVNARDNDGETPLHLAAENGHLEIVKLLLEAGADVNAKDNDGKTALDLAAENGNLEIVKLLLEAG 242
Gem1 COG1100
GTPase SAR1 family domain [General function prediction only];
70-228 9.16e-09

GTPase SAR1 family domain [General function prediction only];


Pssm-ID: 440717 [Multi-domain]  Cd Length: 177  Bit Score: 55.76  E-value: 9.16e-09
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564359681  70 ELRLGVLGDVRSGKSSLIHRFLTGSYQvLEKPES----EQYKKEMLVDGQT-HLVLI----REEAGAPDAKFSGW---AD 137
Cdd:COG1100    3 EKKIVVVGTGGVGKTSLVNRLVGDIFS-LEKYLStngvTIDKKELKLDGLDvDLVIWdtpgQDEFRETRQFYARQltgAS 81
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564359681 138 AVIFVFSLEDESSFQAVSHLHGQLISLRGEGRgglaLALVGTQ-DRISAssPRVVGDARARALCTDMKRCSYYETCATYG 216
Cdd:COG1100   82 LYLFVVDGTREETLQSLYELLESLRRLGKKSP----IILVLNKiDLYDE--EEIEDEERLKEALSEDNIVEVVATSAKTG 155
                        170
                 ....*....|..
gi 564359681 217 LNVDRVFQEVAQ 228
Cdd:COG1100  156 EGVEELFAALAE 167
ArfGap_AGFG2 cd17903
ArfGAP domain of AGFG2 (ArfGAP domain and FG repeat-containing protein 2); The ArfGAP domain ...
586-684 2.95e-08

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: 52.68  E-value: 2.95e-08
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564359681 586 GNSTCVDCGAPNPTWASLNLGALICIECSGIHRNLGTHlSRVRSLDLDDWPRELTLVLTAIGNDTANRVWESDTRGRAKP 665
Cdd:cd17903   13 ANRHCFECAQRGVTYVDITVGSFVCTTCSGLLRGLNPP-HRVKSISMTTFTEPEVLFLQARGNEVCRKIWLGLFDARTSL 91
                         90       100
                 ....*....|....*....|
gi 564359681 666 TRDSSREER-ESWIRAKYEQ 684
Cdd:cd17903   92 IPDSRDPQKvKEFLQEKYEK 111
Rhes_like cd04143
Ras homolog enriched in striatum (Rhes) and activator of G-protein signaling 1 (Dexras1/AGS1); ...
72-227 3.67e-08

Ras homolog enriched in striatum (Rhes) and activator of G-protein signaling 1 (Dexras1/AGS1); This subfamily includes Rhes (Ras homolog enriched in striatum) and Dexras1/AGS1 (activator of G-protein signaling 1). These proteins are homologous, but exhibit significant differences in tissue distribution and subcellular localization. Rhes is found primarily in the striatum of the brain, but is also expressed in other areas of the brain, such as the cerebral cortex, hippocampus, inferior colliculus, and cerebellum. Rhes expression is controlled by thyroid hormones. In rat PC12 cells, Rhes is farnesylated and localizes to the plasma membrane. Rhes binds and activates PI3K, and plays a role in coupling serpentine membrane receptors with heterotrimeric G-protein signaling. Rhes has recently been shown to be reduced under conditions of dopamine supersensitivity and may play a role in determining dopamine receptor sensitivity. Dexras1/AGS1 is a dexamethasone-induced Ras protein that is expressed primarily in the brain, with low expression levels in other tissues. Dexras1 localizes primarily to the cytoplasm, and is a critical regulator of the circadian master clock to photic and nonphotic input. Most Ras proteins contain a lipid modification site at the C-terminus, with a typical sequence motif CaaX, where a = an aliphatic amino acid and X = any amino acid. Lipid binding is essential for membrane attachment, a key feature of most Ras proteins.


Pssm-ID: 133343 [Multi-domain]  Cd Length: 247  Bit Score: 55.14  E-value: 3.67e-08
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564359681  72 RLGVLGDVRSGKSSLIHRFLTGSYQVLEKPESEQY-KKEMLVDGQTHLVLIREEAGAPD--AK-----FSGwaDAVIFVF 143
Cdd:cd04143    2 RMVVLGASKVGKTAIVSRFLGGRFEEQYTPTIEDFhRKLYSIRGEVYQLDILDTSGNHPfpAMrrlsiLTG--DVFILVF 79
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564359681 144 SLEDESSFQAVSHLHGQLIS----LRGEGRGGLALALVGTQDRISASSPRVVGDARARALCTDMKRCSYYETCATYGLNV 219
Cdd:cd04143   80 SLDNRESFEEVCRLREQILEtkscLKNKTKENVKIPMVICGNKADRDFPREVQRDEVEQLVGGDENCAYFEVSAKKNSNL 159

                 ....*...
gi 564359681 220 DRVFQEVA 227
Cdd:cd04143  160 DEMFRALF 167
RGK cd04148
Rem, Rem2, Rad, Gem/Kir (RGK) subfamily of Ras GTPases; RGK subfamily. The RGK (Rem, Rem2, Rad, ...
71-236 5.22e-08

Rem, Rem2, Rad, Gem/Kir (RGK) subfamily of Ras GTPases; RGK subfamily. The RGK (Rem, Rem2, Rad, Gem/Kir) subfamily of Ras GTPases are expressed in a tissue-specific manner and are dynamically regulated by transcriptional and posttranscriptional mechanisms in response to environmental cues. RGK proteins bind to the beta subunit of L-type calcium channels, causing functional down-regulation of these voltage-dependent calcium channels, and either termination of calcium-dependent secretion or modulation of electrical conduction and contractile function. Inhibition of L-type calcium channels by Rem2 may provide a mechanism for modulating calcium-triggered exocytosis in hormone-secreting cells, and has been proposed to influence the secretion of insulin in pancreatic beta cells. RGK proteins also interact with and inhibit the Rho/Rho kinase pathway to modulate remodeling of the cytoskeleton. Two characteristics of RGK proteins cited in the literature are N-terminal and C-terminal extensions beyond the GTPase domain typical of Ras superfamily members. The N-terminal extension is not conserved among family members; the C-terminal extension is reported to be conserved among the family and lack the CaaX prenylation motif typical of membrane-associated Ras proteins. However, a putative CaaX motif has been identified in the alignment of the C-terminal residues of this CD.


Pssm-ID: 206715 [Multi-domain]  Cd Length: 219  Bit Score: 54.33  E-value: 5.22e-08
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564359681  71 LRLGVLGDVRSGKSSLIHRFLTGSYQVLEKPES--EQYKKEMLVDGQ-THLVLIreeaGAPDAKFSGW--------ADAV 139
Cdd:cd04148    1 YRVVLLGDSGVGKSSLANIFTAGVYEDSAYEASgdDTYERTVSVDGEeATLVVY----DHWEQEDGMWledscmqvGDAY 76
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564359681 140 IFVFSLEDESSFQAVSHLhgqLISLRgEGRGGLALA--LVGTQDRISASspRVVGDARARAlCTDMKRCSYYETCATYGL 217
Cdd:cd04148   77 VIVYSVTDRSSFEKASEL---RIQLR-RARQAEDIPiiLVGNKSDLVRS--REVSVQEGRA-CAVVFDCKFIETSAALQH 149
                        170
                 ....*....|....*....
gi 564359681 218 NVDRVFqEVAQKVVTLRKQ 236
Cdd:cd04148  150 NVDELF-EGIVRQVRLRRD 167
Ank_2 pfam12796
Ankyrin repeats (3 copies);
739-790 2.82e-07

Ankyrin repeats (3 copies);


Pssm-ID: 463710 [Multi-domain]  Cd Length: 91  Bit Score: 48.96  E-value: 2.82e-07
                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|..
gi 564359681  739 LHLAAELAHVVITQLLLWYGADVAARDAQGRTALFYARQAGSQLCADILLQH 790
Cdd:pfam12796   1 LHLAAKNGNLELVKLLLENGADANLQDKNGRTALHLAAKNGHLEIVKLLLEH 52
RalA_RalB cd04139
Ral (Ras-like) family containing highly homologous RalA and RalB; The Ral (Ras-like) subfamily ...
82-230 4.51e-07

Ral (Ras-like) family containing highly homologous RalA and RalB; The Ral (Ras-like) subfamily consists of the highly homologous RalA and RalB. Ral proteins are believed to play a crucial role in tumorigenesis, metastasis, endocytosis, and actin cytoskeleton dynamics. Despite their high sequence similarity (>80% sequence identity), nonoverlapping and opposing functions have been assigned to RalA and RalBs in tumor migration. In human bladder and prostate cancer cells, RalB promotes migration while RalA inhibits it. A Ral-specific set of GEFs has been identified that are activated by Ras binding. This RalGEF activity is enhanced by Ras binding to another of its target proteins, phosphatidylinositol 3-kinase (PI3K). Ral effectors include RLIP76/RalBP1, a Rac/cdc42 GAP, and the exocyst (Sec6/8) complex, a heterooctomeric protein complex that is involved in tethering vesicles to specific sites on the plasma membrane prior to exocytosis. In rat kidney cells, RalB is required for functional assembly of the exocyst and for localizing the exocyst to the leading edge of migrating cells. In human cancer cells, RalA is required to support anchorage-independent proliferation and RalB is required to suppress apoptosis. RalA has been shown to localize to the plasma membrane while RalB is localized to the intracellular vesicles. Most Ras proteins contain a lipid modification site at the C-terminus, with a typical sequence motif CaaX, where a = an aliphatic amino acid and X = any amino acid. Lipid binding is essential for membrane attachment, a key feature of most Ras proteins. Due to the presence of truncated sequences in this CD, the lipid modification site is not available for annotation.


Pssm-ID: 206710 [Multi-domain]  Cd Length: 163  Bit Score: 50.50  E-value: 4.51e-07
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564359681  82 GKSSLIHRFLTGSYQVLEKP-ESEQYKKEMLVDGQTHLVLIREEAGAPDAK-----FSGWADAVIFVFSLEDESSFQAVS 155
Cdd:cd04139   12 GKSALTLQFMYDEFVEDYEPtKADSYRKKVVLDGEEVQLNILDTAGQEDYAairdnYFRSGEGFLLVFSITDMESFTALA 91
                         90       100       110       120       130       140       150
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 564359681 156 HLHGQLISLRGEGRggLALALVGtqDRISASSPRVVGDARARALCTDMKrCSYYETCATYGLNVDRVFQEVAQKV 230
Cdd:cd04139   92 EFREQILRVKEDDN--VPLLLVG--NKCDLEDKRQVSVEEAANLAEQWG-VNYVETSAKTRANVDKVFFDLVREI 161
H_N_K_Ras_like cd04138
Ras GTPase family containing H-Ras,N-Ras and K-Ras4A/4B; H-Ras/N-Ras/K-Ras subfamily. H-Ras, ...
70-223 7.66e-07

Ras GTPase family containing H-Ras,N-Ras and K-Ras4A/4B; H-Ras/N-Ras/K-Ras subfamily. H-Ras, N-Ras, and K-Ras4A/4B are the prototypical members of the Ras family. These isoforms generate distinct signal outputs despite interacting with a common set of activators and effectors, and are strongly associated with oncogenic progression in tumor initiation. Mutated versions of Ras that are insensitive to GAP stimulation (and are therefore constitutively active) are found in a significant fraction of human cancers. Many Ras guanine nucleotide exchange factors (GEFs) have been identified. They are sequestered in the cytosol until activation by growth factors triggers recruitment to the plasma membrane or Golgi, where the GEF colocalizes with Ras. Active (GTP-bound) Ras interacts with several effector proteins that stimulate a variety of diverse cytoplasmic signaling activities. Some are known to positively mediate the oncogenic properties of Ras, including Raf, phosphatidylinositol 3-kinase (PI3K), RalGEFs, and Tiam1. Others are proposed to play negative regulatory roles in oncogenesis, including RASSF and NORE/MST1. Most Ras proteins contain a lipid modification site at the C-terminus, with a typical sequence motif CaaX, where a = an aliphatic amino acid and X = any amino acid. Lipid binding is essential for membrane attachment, a key feature of most Ras proteins. Due to the presence of truncated sequences in this CD, the lipid modification site is not available for annotation.


Pssm-ID: 133338 [Multi-domain]  Cd Length: 162  Bit Score: 49.72  E-value: 7.66e-07
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564359681  70 ELRLGVLGDVRSGKSSLIHRFLTGSYQVLEKPESE-QYKKEMLVDGQTHLVLI-----REEAGAPDAKFSGWADAVIFVF 143
Cdd:cd04138    1 EYKLVVVGAGGVGKSALTIQLIQNHFVDEYDPTIEdSYRKQVVIDGETCLLDIldtagQEEYSAMRDQYMRTGEGFLCVF 80
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564359681 144 SLEDESSFQAVSHLHGQLisLRGEGRGGLALALVGTQDRISAsspRVVGDARARALCTDMKrCSYYETCATYGLNVDRVF 223
Cdd:cd04138   81 AINSRKSFEDIHTYREQI--KRVKDSDDVPMVLVGNKCDLAA---RTVSTRQGQDLAKSYG-IPYIETSAKTRQGVEEAF 154
Ank_2 pfam12796
Ankyrin repeats (3 copies);
727-792 7.87e-07

Ankyrin repeats (3 copies);


Pssm-ID: 463710 [Multi-domain]  Cd Length: 91  Bit Score: 47.80  E-value: 7.87e-07
                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 564359681  727 DTSVEDPQLRSPLHLAAELAHVVITQLLLWYgADVAARDaQGRTALFYARQAGSQLCADILLQHGC 792
Cdd:pfam12796  22 DANLQDKNGRTALHLAAKNGHLEIVKLLLEH-ADVNLKD-NGRTALHYAARSGHLEIVKLLLEKGA 85
Rab21 cd04123
Rab GTPase family 21 (Rab21); The localization and function of Rab21 are not clearly defined, ...
76-231 1.11e-06

Rab GTPase family 21 (Rab21); The localization and function of Rab21 are not clearly defined, with conflicting data reported. Rab21 has been reported to localize in the ER in human intestinal epithelial cells, with partial colocalization with alpha-glucosidase, a late endosomal/lysosomal marker. More recently, Rab21 was shown to colocalize with and affect the morphology of early endosomes. In Dictyostelium, GTP-bound Rab21, together with two novel LIM domain proteins, LimF and ChLim, has been shown to regulate phagocytosis. GTPase activating proteins (GAPs) interact with GTP-bound Rab and accelerate the hydrolysis of GTP to GDP. Guanine nucleotide exchange factors (GEFs) interact with GDP-bound Rabs to promote the formation of the GTP-bound state. Rabs are further regulated by guanine nucleotide dissociation inhibitors (GDIs), which facilitate Rab recycling by masking C-terminal lipid binding and promoting cytosolic localization. Most Rab GTPases contain a lipid modification site at the C-terminus, with sequence motifs CC, CXC, or CCX. Lipid binding is essential for membrane attachment, a key feature of most Rab proteins. Due to the presence of truncated sequences in this CD, the lipid modification site is not available for annotation.


Pssm-ID: 133323 [Multi-domain]  Cd Length: 162  Bit Score: 49.14  E-value: 1.11e-06
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564359681  76 LGDVRSGKSSLIHRFLTGSYQvlEKPESE-----QYKKEMLVDGQTHLVlIREEAG-------AP----DakfsgwADAV 139
Cdd:cd04123    6 LGEGRVGKTSLVLRYVENKFN--EKHESTtqasfFQKTVNIGGKRIDLA-IWDTAGqeryhalGPiyyrD------ADGA 76
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564359681 140 IFVFSLEDESSFQAVSHLHGQLISLRGEgrgGLALALVGtqDRISASSPRVVGDARARALCTDMKrCSYYETCATYGLNV 219
Cdd:cd04123   77 ILVYDITDADSFQKVKKWIKELKQMRGN---NISLVIVG--NKIDLERQRVVSKSEAEEYAKSVG-AKHFETSAKTGKGI 150
                        170
                 ....*....|..
gi 564359681 220 DRVFQEVAQKVV 231
Cdd:cd04123  151 EELFLSLAKRMI 162
Wrch_1 cd04130
Wnt-1 responsive Cdc42 homolog (Wrch-1) is a Rho family GTPase similar to Cdc42; Wrch-1 (Wnt-1 ...
76-223 1.82e-06

Wnt-1 responsive Cdc42 homolog (Wrch-1) is a Rho family GTPase similar to Cdc42; Wrch-1 (Wnt-1 responsive Cdc42 homolog) is a Rho family GTPase that shares significant sequence and functional similarity with Cdc42. Wrch-1 was first identified in mouse mammary epithelial cells, where its transcription is upregulated in Wnt-1 transformation. Wrch-1 contains N- and C-terminal extensions relative to cdc42, suggesting potential differences in cellular localization and function. The Wrch-1 N-terminal extension contains putative SH3 domain-binding motifs and has been shown to bind the SH3 domain-containing protein Grb2, which increases the level of active Wrch-1 in cells. Unlike Cdc42, which localizes to the cytosol and perinuclear membranes, Wrch-1 localizes extensively with the plasma membrane and endosomes. The membrane association, localization, and biological activity of Wrch-1 indicate an atypical model of regulation distinct from other Rho family GTPases. Most Rho proteins contain a lipid modification site at the C-terminus, with a typical sequence motif CaaX, where a = an aliphatic amino acid and X = any amino acid. Lipid binding is essential for membrane attachment, a key feature of most Rho proteins. Due to the presence of truncated sequences in this CD, the lipid modification site is not available for annotation.


Pssm-ID: 133330 [Multi-domain]  Cd Length: 173  Bit Score: 48.94  E-value: 1.82e-06
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564359681  76 LGDVRSGKSSLIHRFLTGSYQVLEKPE-SEQYKKEMLVDGQ-THLVLIrEEAGAPDakFSGW-------ADAVIFVFSLE 146
Cdd:cd04130    6 VGDGAVGKTSLIVSYTTNGYPTEYVPTaFDNFSVVVLVDGKpVRLQLC-DTAGQDE--FDKLrplcypdTDVFLLCFSVV 82
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564359681 147 DESSFQAVSHlhgQLISLRGEGRGGLALALVGTQ----------DRISASSPRVVGDARARALCTDMKRCSYYETCATYG 216
Cdd:cd04130   83 NPSSFQNISE---KWIPEIRKHNPKAPIILVGTQadlrtdvnvlIQLARYGEKPVSQSRAKALAEKIGACEYIECSALTQ 159

                 ....*..
gi 564359681 217 LNVDRVF 223
Cdd:cd04130  160 KNLKEVF 166
RRP22 cd04142
Ras-related protein on chromosome 22 (RRP22) family; RRP22 (Ras-related protein on chromosome ...
71-235 2.11e-06

Ras-related protein on chromosome 22 (RRP22) family; RRP22 (Ras-related protein on chromosome 22) subfamily consists of proteins that inhibit cell growth and promote caspase-independent cell death. Unlike most Ras proteins, RRP22 is down-regulated in many human tumor cells due to promoter methylation. RRP22 localizes to the nucleolus in a GTP-dependent manner, suggesting a novel function in modulating transport of nucleolar components. Most Ras proteins contain a lipid modification site at the C-terminus, with a typical sequence motif CaaX, where a = an aliphatic amino acid and X = any amino acid. Lipid binding is essential for membrane attachment, a key feature of most Ras proteins. Like most Ras family proteins, RRP22 is farnesylated.


Pssm-ID: 133342 [Multi-domain]  Cd Length: 198  Bit Score: 49.10  E-value: 2.11e-06
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564359681  71 LRLGVLGDVRSGKSSLIHRFLTGSYQVLEKPES--EQYKKEMLVDGQTHLVLIREEAGA-----------PDAKFSGW-- 135
Cdd:cd04142    1 VRVAVLGAPGVGKTAIVRQFLAQEFPEEYIPTEhrRLYRPAVVLSGRVYDLHILDVPNMqrypgtagqewMDPRFRGLrn 80
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564359681 136 ADAVIFVFSLEDESSFQAVSHLHGQLISLRGEGRGGLALALVGTQ-DRisaSSPRVVGDARARALCTDMKRCSYYETCAT 214
Cdd:cd04142   81 SRAFILVYDICSPDSFHYVKLLRQQILETRPAGNKEPPIVVVGNKrDQ---QRHRFAPRHVLSVLVRKSWKCGYLECSAK 157
                        170       180
                 ....*....|....*....|.
gi 564359681 215 YGLNVDRVFQEVAQKVVTLRK 235
Cdd:cd04142  158 YNWHILLLFKELLISATTRGR 178
Rab5_related cd01860
Rab-related GTPase family includes Rab5 and Rab22; regulates early endosome fusion; The ...
70-230 4.22e-06

Rab-related GTPase family includes Rab5 and Rab22; regulates early endosome fusion; The Rab5-related subfamily includes Rab5 and Rab22 of mammals, Ypt51/Ypt52/Ypt53 of yeast, and RabF of plants. The members of this subfamily are involved in endocytosis and endocytic-sorting pathways. In mammals, Rab5 GTPases localize to early endosomes and regulate fusion of clathrin-coated vesicles to early endosomes and fusion between early endosomes. In yeast, Ypt51p family members similarly regulate membrane trafficking through prevacuolar compartments. GTPase activating proteins (GAPs) interact with GTP-bound Rab and accelerate the hydrolysis of GTP to GDP. Guanine nucleotide exchange factors (GEFs) interact with GDP-bound Rabs to promote the formation of the GTP-bound state. Rabs are further regulated by guanine nucleotide dissociation inhibitors (GDIs), which facilitate Rab recycling by masking C-terminal lipid binding and promoting cytosolic localization. Most Rab GTPases contain a lipid modification site at the C-terminus, with sequence motifs CC, CXC, or CCX. Lipid binding is essential for membrane attachment, a key feature of most Rab proteins. Due to the presence of truncated sequences in this CD, the lipid modification site is not available for annotation.


Pssm-ID: 206653 [Multi-domain]  Cd Length: 163  Bit Score: 47.55  E-value: 4.22e-06
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564359681  70 ELRLGVLGDVRSGKSSLIHRFLTGSYqvLEKPESEQ----YKKEMLVDGQTHLVLIREEAG-------APdAKFSGwADA 138
Cdd:cd01860    1 QFKLVLLGDSSVGKSSIVLRFVKNEF--SENQESTIgaafLTQTVNLDDTTVKFEIWDTAGqeryrslAP-MYYRG-AAA 76
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564359681 139 VIFVFSLEDESSFQAVSHLhgqLISLRGEGRGGLALALVGtqDRISASSPRVVGDARARALCTDMKrCSYYETCATYGLN 218
Cdd:cd01860   77 AIVVYDITSEESFEKAKSW---VKELQEHGPPNIVIALAG--NKADLESKRQVSTEEAQEYADENG-LLFMETSAKTGEN 150
                        170
                 ....*....|..
gi 564359681 219 VDRVFQEVAQKV 230
Cdd:cd01860  151 VNELFTEIARKL 162
Ank_5 pfam13857
Ankyrin repeats (many copies);
722-775 5.14e-06

Ankyrin repeats (many copies);


Pssm-ID: 433530 [Multi-domain]  Cd Length: 56  Bit Score: 44.26  E-value: 5.14e-06
                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....
gi 564359681  722 RHGPLDTSVEDPQLRSPLHLAAELAHVVITQLLLWYGADVAARDAQGRTALFYA 775
Cdd:pfam13857   3 EHGPIDLNRLDGEGYTPLHVAAKYGALEIVRVLLAYGVDLNLKDEEGLTALDLA 56
PH cd00821
Pleckstrin homology (PH) domain; PH domains have diverse functions, but in general are ...
491-549 5.66e-06

Pleckstrin homology (PH) domain; PH domains have diverse functions, but in general are involved in targeting proteins to the appropriate cellular location or in the interaction with a binding partner. They share little sequence conservation, but all have a common fold, which is electrostatically polarized. Less than 10% of PH domains bind phosphoinositide phosphates (PIPs) with high affinity and specificity. PH domains are distinguished from other PIP-binding domains by their specific high-affinity binding to PIPs with two vicinal phosphate groups: PtdIns(3,4)P2, PtdIns(4,5)P2 or PtdIns(3,4,5)P3 which results in targeting some PH domain proteins to the plasma membrane. A few display strong specificity in lipid binding. Any specificity is usually determined by loop regions or insertions in the N-terminus of the domain, which are not conserved across all PH domains. PH domains are found in cellular signaling proteins such as serine/threonine kinase, tyrosine kinases, regulators of G-proteins, endocytotic GTPases, adaptors, as well as cytoskeletal associated molecules and in lipid associated enzymes.


Pssm-ID: 275388 [Multi-domain]  Cd Length: 92  Bit Score: 45.23  E-value: 5.66e-06
                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|....*....
gi 564359681 491 SPMVKKQRRKKLSTPSKTEGSAVQAEEENFEFLIVSSTGQTWHFEAASFEERDAWVQAI 549
Cdd:cd00821   34 KKDSSYKPKGSIPLSGILEVEEVSPKERPHCFELVTPDGRTYYLQADSEEERQEWLKAL 92
PLN03131 PLN03131
hypothetical protein; Provisional
568-682 7.42e-06

hypothetical protein; Provisional


Pssm-ID: 178677 [Multi-domain]  Cd Length: 705  Bit Score: 49.78  E-value: 7.42e-06
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564359681 568 RTDSQSEAVAIQAIRNAKGNSTCVDCGAPNPTWASLNLGALICIECSGIHRNLgTHlsRVRSLDLDDWPRELTLVLTAIG 647
Cdd:PLN03131   4 RKEEERNEKIIRGLMKLPPNRRCINCNSLGPQFVCTNFWTFICMTCSGIHREF-TH--RVKSVSMSKFTSQDVEALQNGG 80
                         90       100       110
                 ....*....|....*....|....*....|....*.
gi 564359681 648 NDTANRVWESDTRGRAKPTRDSSREER-ESWIRAKY 682
Cdd:PLN03131  81 NQRAREIYLKDWDQQRQRLPDNSKVDKiREFIKDIY 116
PH1_Pleckstrin_2 cd13301
Pleckstrin 2 Pleckstrin homology (PH) domain, repeat 1; Pleckstrin is a protein found in ...
520-566 8.97e-06

Pleckstrin 2 Pleckstrin homology (PH) domain, repeat 1; Pleckstrin is a protein found in platelets. This name is derived from platelet and leukocyte C kinase substrate and the KSTR string of amino acids. Pleckstrin 2 contains two PH domains and a DEP (dishvelled, egl-10, and pleckstrin) domain. Unlike pleckstrin 1, pleckstrin 2 does not contain obvious sites of PKC phosphorylation. Pleckstrin 2 plays a role in actin rearrangement, large lamellipodia and peripheral ruffle formation, and may help orchestrate cytoskeletal arrangement. The PH domains of pleckstrin 2 are thought to contribute to lamellipodia formation. This cd contains the first PH domain repeat. PH domains have diverse functions, but in general are involved in targeting proteins to the appropriate cellular location or in the interaction with a binding partner. They share little sequence conservation, but all have a common fold, which is electrostatically polarized. Less than 10% of PH domains bind phosphoinositide phosphates (PIPs) with high affinity and specificity. PH domains are distinguished from other PIP-binding domains by their specific high-affinity binding to PIPs with two vicinal phosphate groups: PtdIns(3,4)P2, PtdIns(4,5)P2 or PtdIns(3,4,5)P3 which results in targeting some PH domain proteins to the plasma membrane. A few display strong specificity in lipid binding. Any specificity is usually determined by loop regions or insertions in the N-terminus of the domain, which are not conserved across all PH domains. PH domains are found in cellular signaling proteins such as serine/threonine kinase, tyrosine kinases, regulators of G-proteins, endocytotic GTPases, adaptors, as well as cytoskeletal associated molecules and in lipid associated enzymes.


Pssm-ID: 270113  Cd Length: 108  Bit Score: 45.44  E-value: 8.97e-06
                         10        20        30        40
                 ....*....|....*....|....*....|....*....|....*..
gi 564359681 520 FEFLIVSSTGQTWHFEAASFEERDAWVQAIESQIlaslQCCESSKVK 566
Cdd:cd13301   65 LVFKLTTAKGQEHFFQACSREERDAWAKDITKAI----TCLEGGKRF 107
PLN03118 PLN03118
Rab family protein; Provisional
75-231 1.08e-05

Rab family protein; Provisional


Pssm-ID: 215587 [Multi-domain]  Cd Length: 211  Bit Score: 47.36  E-value: 1.08e-05
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564359681  75 VLGDVRSGKSSLIHRFLTGSYQVLEKPESEQYK-KEMLVDGQTHLVLIREEAGAP-----DAKFSGWADAVIFVFSLEDE 148
Cdd:PLN03118  19 LIGDSGVGKSSLLVSFISSSVEDLAPTIGVDFKiKQLTVGGKRLKLTIWDTAGQErfrtlTSSYYRNAQGIILVYDVTRR 98
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564359681 149 SSFQAVSHLHGQLISLRGEGRGGLALaLVGtqDRISASSPRVVGDARARALCTDMKrCSYYETCATYGLNVDRVFQEVAQ 228
Cdd:PLN03118  99 ETFTNLSDVWGKEVELYSTNQDCVKM-LVG--NKVDRESERDVSREEGMALAKEHG-CLFLECSAKTRENVEQCFEELAL 174

                 ...
gi 564359681 229 KVV 231
Cdd:PLN03118 175 KIM 177
RheB cd04137
Ras Homolog Enriched in Brain (RheB) is a small GTPase; Rheb (Ras Homolog Enriched in Brain) ...
75-230 1.08e-05

Ras Homolog Enriched in Brain (RheB) is a small GTPase; Rheb (Ras Homolog Enriched in Brain) subfamily. Rheb was initially identified in rat brain, where its expression is elevated by seizures or by long-term potentiation. It is expressed ubiquitously, with elevated levels in muscle and brain. Rheb functions as an important mediator between the tuberous sclerosis complex proteins, TSC1 and TSC2, and the mammalian target of rapamycin (TOR) kinase to stimulate cell growth. TOR kinase regulates cell growth by controlling nutrient availability, growth factors, and the energy status of the cell. TSC1 and TSC2 form a dimeric complex that has tumor suppressor activity, and TSC2 is a GTPase activating protein (GAP) for Rheb. The TSC1/TSC2 complex inhibits the activation of TOR kinase through Rheb. Rheb has also been shown to induce the formation of large cytoplasmic vacuoles in a process that is dependent on the GTPase cycle of Rheb, but independent of the TOR kinase, suggesting Rheb plays a role in endocytic trafficking that leads to cell growth and cell-cycle progression. Most Ras proteins contain a lipid modification site at the C-terminus, with a typical sequence motif CaaX, where a = an aliphatic amino acid and X = any amino acid. Lipid binding is essential for membrane attachment, a key feature of most Ras proteins.


Pssm-ID: 206709 [Multi-domain]  Cd Length: 180  Bit Score: 46.86  E-value: 1.08e-05
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564359681  75 VLGDVRSGKSSLIHRFLTGSYqvlekPES------EQYKKEMLVDGQTHLVLIREEAGAPD-----AKFSGWADAVIFVF 143
Cdd:cd04137    6 VLGSRSVGKSSLTVQFVEGHF-----VESyyptieNTFSKIITYKGQEYHLEIVDTAGQDEysilpQKYSIGIHGYILVY 80
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564359681 144 SLEDESSFQAVSHLHGQLisLRGEGRGGLALALVGTqdRISASSPRVVGDARARALCTDMKrCSYYETCATYGLNVDRVF 223
Cdd:cd04137   81 SVTSRKSFEVVKVIYDKI--LDMLGKESVPIVLVGN--KSDLHMERQVSAEEGKKLAESWG-AAFLESSAKENENVEEAF 155

                 ....*..
gi 564359681 224 QEVAQKV 230
Cdd:cd04137  156 ELLIEEI 162
ARHI_like cd04140
A Ras homolog member I (ARHI); ARHI (A Ras homolog member I) is a member of the Ras family ...
72-226 1.60e-05

A Ras homolog member I (ARHI); ARHI (A Ras homolog member I) is a member of the Ras family with several unique structural and functional properties. ARHI is expressed in normal human ovarian and breast tissue, but its expression is decreased or eliminated in breast and ovarian cancer. ARHI contains an N-terminal extension of 34 residues (human) that is required to retain its tumor suppressive activity. Unlike most other Ras family members, ARHI is maintained in the constitutively active (GTP-bound) state in resting cells and has modest GTPase activity. ARHI inhibits STAT3 (signal transducers and activators of transcription 3), a latent transcription factor whose abnormal activation plays a critical role in oncogenesis. Most Ras proteins contain a lipid modification site at the C-terminus, with a typical sequence motif CaaX, where a = an aliphatic amino acid and X = any amino acid. Lipid binding is essential for membrane attachment, a key feature of most Ras proteins. Due to the presence of truncated sequences in this CD, the lipid modification site is not available for annotation.


Pssm-ID: 206711 [Multi-domain]  Cd Length: 165  Bit Score: 45.97  E-value: 1.60e-05
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564359681  72 RLGVLGDVRSGKSSLIHRFLTGSYQVLEKPESEQYKKEMLVDGQTHLVL-IREEAGApdAKFSGW-------ADAVIFVF 143
Cdd:cd04140    3 RVVVFGAGGVGKSSLVLRFVKGTFRESYIPTIEDTYRQVISCSKSICTLqITDTTGS--HQFPAMqrlsiskGHAFILVY 80
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564359681 144 SLEDESSFQAVSHLHGQLISLRGEGRGGLALALVGtqDRISASSPRVVGDARARALCTDMKrCSYYETCATYGLNVDRVF 223
Cdd:cd04140   81 SITSKQSLEELKPIYELICEIKGNNLEKIPIMLVG--NKCDESPSREVSSSEGAALARTWN-CAFMETSAKTNHNVQELF 157

                 ...
gi 564359681 224 QEV 226
Cdd:cd04140  158 QEL 160
PTZ00322 PTZ00322
6-phosphofructo-2-kinase/fructose-2,6-biphosphatase; Provisional
724-797 2.67e-05

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


Pssm-ID: 140343 [Multi-domain]  Cd Length: 664  Bit Score: 47.97  E-value: 2.67e-05
                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 564359681 724 GPLDTSVEDPQLRSPLHLAAELAHVVITQLLLWYGADVAARDAQGRTALFYARQAGSQLCADILLQHG-CPGEGG 797
Cdd:PTZ00322 104 GGADPNCRDYDGRTPLHIACANGHVQVVRVLLEFGADPTLLDKDGKTPLELAEENGFREVVQLLSRHSqCHFELG 178
PLN03119 PLN03119
putative ADP-ribosylation factor GTPase-activating protein AGD14; Provisional
568-684 3.20e-05

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


Pssm-ID: 178666  Cd Length: 648  Bit Score: 47.53  E-value: 3.20e-05
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564359681 568 RTDSQSEAVaIQAIRNAKGNSTCVDCGAPNPTWASLNLGALICIECSGIHRNLgTHlsRVRSLDLDDWPRELTLVLTAIG 647
Cdd:PLN03119   5 REEERNEKI-IRGLMKLPPNRRCINCNSLGPQYVCTTFWTFVCMACSGIHREF-TH--RVKSVSMSKFTSKEVEVLQNGG 80
                         90       100       110
                 ....*....|....*....|....*....|....*...
gi 564359681 648 NDTANRVWESD-TRGRAKPTRDSSREERESWIRAKYEQ 684
Cdd:PLN03119  81 NQRAREIYLKNwDHQRQRLPENSNAERVREFIKNVYVQ 118
Ank_4 pfam13637
Ankyrin repeats (many copies);
736-775 4.16e-05

Ankyrin repeats (many copies);


Pssm-ID: 372654 [Multi-domain]  Cd Length: 54  Bit Score: 41.88  E-value: 4.16e-05
                          10        20        30        40
                  ....*....|....*....|....*....|....*....|
gi 564359681  736 RSPLHLAAELAHVVITQLLLWYGADVAARDAQGRTALFYA 775
Cdd:pfam13637   2 LTALHAAAASGHLELLRLLLEKGADINAVDGNGETALHFA 41
RJL cd04119
Rab GTPase family J-like (RabJ-like); RJLs are found in many protists and as chimeras with ...
75-224 5.85e-05

Rab GTPase family J-like (RabJ-like); RJLs are found in many protists and as chimeras with C-terminal DNAJ domains in deuterostome metazoa. They are not found in plants, fungi, and protostome metazoa, suggesting a horizontal gene transfer between protists and deuterostome metazoa. RJLs lack any known membrane targeting signal and contain a degenerate phosphate/magnesium-binding 3 (PM3) motif, suggesting an impaired ability to hydrolyze GTP. GTPase activating proteins (GAPs) interact with GTP-bound Rab and accelerate the hydrolysis of GTP to GDP. Guanine nucleotide exchange factors (GEFs) interact with GDP-bound Rabs to promote the formation of the GTP-bound state. Rabs are further regulated by guanine nucleotide dissociation inhibitors (GDIs), which facilitate Rab recycling by masking C-terminal lipid binding and promoting cytosolic localization.


Pssm-ID: 133319 [Multi-domain]  Cd Length: 168  Bit Score: 44.27  E-value: 5.85e-05
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564359681  75 VLGDVRSGKSSLIHRFLTG------------SYQVlekpeseqykKEMLVDGQTHLVLIREEAGAPD-----AKFSGWAD 137
Cdd:cd04119    5 SMGNSGVGKSCIIKRYCEGrfvskylptigiDYGV----------KKVSVRNKEVRVNFFDLSGHPEylevrNEFYKDTQ 74
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564359681 138 AVIFVFSLEDESSFQAVSHLHGQLISLRGEGRGGLALALVGTQDRISASSPRVVGDARARALCTDmKRCSYYETCATYGL 217
Cdd:cd04119   75 GVLLVYDVTDRQSFEALDSWLKEMKQEGGPHGNMENIVVVVCANKIDLTKHRAVSEDEGRLWAES-KGFKYFETSACTGE 153

                 ....*..
gi 564359681 218 NVDRVFQ 224
Cdd:cd04119  154 GVNEMFQ 160
PH smart00233
Pleckstrin homology domain; Domain commonly found in eukaryotic signalling proteins. The ...
516-553 6.67e-05

Pleckstrin homology domain; Domain commonly found in eukaryotic signalling proteins. The domain family possesses multiple functions including the abilities to bind inositol phosphates, and various proteins. PH domains have been found to possess inserted domains (such as in PLC gamma, syntrophins) and to be inserted within other domains. Mutations in Brutons tyrosine kinase (Btk) within its PH domain cause X-linked agammaglobulinaemia (XLA) in patients. Point mutations cluster into the positively charged end of the molecule around the predicted binding site for phosphatidylinositol lipids.


Pssm-ID: 214574 [Multi-domain]  Cd Length: 102  Bit Score: 42.54  E-value: 6.67e-05
                           10        20        30
                   ....*....|....*....|....*....|....*...
gi 564359681   516 EEENFEFLIVSSTGQTWHFEAASFEERDAWVQAIESQI 553
Cdd:smart00233  64 SKKPHCFEIKTSDRKTLLLQAESEEEREKWVEALRKAI 101
Rab28 cd04109
Rab GTPase family 28 (Rab28); Rab28 subfamily. First identified in maize, Rab28 has been shown ...
71-238 8.83e-05

Rab GTPase family 28 (Rab28); Rab28 subfamily. First identified in maize, Rab28 has been shown to be a late embryogenesis-abundant (Lea) protein that is regulated by the plant hormone abcisic acid (ABA). In Arabidopsis, Rab28 is expressed during embryo development and is generally restricted to provascular tissues in mature embryos. Unlike maize Rab28, it is not ABA-inducible. Characterization of the human Rab28 homolog revealed two isoforms, which differ by a 95-base pair insertion, producing an alternative sequence for the 30 amino acids at the C-terminus. The two human isoforms are presumably the result of alternative splicing. Since they differ at the C-terminus but not in the GTP-binding region, they are predicted to be targeted to different cellular locations. GTPase activating proteins (GAPs) interact with GTP-bound Rab and accelerate the hydrolysis of GTP to GDP. Guanine nucleotide exchange factors (GEFs) interact with GDP-bound Rabs to promote the formation of the GTP-bound state. Rabs are further regulated by guanine nucleotide dissociation inhibitors (GDIs), which facilitate Rab recycling by masking C-terminal lipid binding and promoting cytosolic localization. Most Rab GTPases contain a lipid modification site at the C-terminus, with sequence motifs CC, CXC, or CCX. Lipid binding is essential for membrane attachment, a key feature of most Rab proteins.


Pssm-ID: 206694 [Multi-domain]  Cd Length: 213  Bit Score: 44.40  E-value: 8.83e-05
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564359681  71 LRLGVLGDVRSGKSSLIHRFLTGSYqvlekpeSEQYKKEMLVDGQTHLVLIREE---------------AGAPDAKFSGW 135
Cdd:cd04109    1 IKIVVLGDGASGKTSLIRRFAQEGF-------GKSYKQTIGLDFFSRRITLPGSlnvtlqvwdiggqqiGGKMLDKYIYG 73
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564359681 136 ADAVIFVFSLEDESSFQAVSHLHGQLISLRGEGRGGLALALVGtqDRISASSPRVVGDARARALCTDMKRCSYYETCATy 215
Cdd:cd04109   74 AQAVCLVYDITNSQSFENLEDWLSVVKKVNEESETKPKMVLVG--NKTDLEHNRQVTAEKHARFAQENDMESIFVSAKT- 150
                        170       180
                 ....*....|....*....|...
gi 564359681 216 GLNVDRVFQEVAQKVVTLRKQQQ 238
Cdd:cd04109  151 GDRVFLCFQRIAAELLGVKLSQA 173
PH smart00233
Pleckstrin homology domain; Domain commonly found in eukaryotic signalling proteins. The ...
341-405 9.94e-05

Pleckstrin homology domain; Domain commonly found in eukaryotic signalling proteins. The domain family possesses multiple functions including the abilities to bind inositol phosphates, and various proteins. PH domains have been found to possess inserted domains (such as in PLC gamma, syntrophins) and to be inserted within other domains. Mutations in Brutons tyrosine kinase (Btk) within its PH domain cause X-linked agammaglobulinaemia (XLA) in patients. Point mutations cluster into the positively charged end of the molecule around the predicted binding site for phosphatidylinositol lipids.


Pssm-ID: 214574 [Multi-domain]  Cd Length: 102  Bit Score: 42.15  E-value: 9.94e-05
                           10        20        30        40        50        60
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 564359681   341 PIKQSFLLKRSGNSlNKEWKKKYVTLsSNGFLLYHPSINDYIHSTHGKEMDLLRTTVKVPGKRPP 405
Cdd:smart00233   1 VIKEGWLYKKSGGG-KKSWKKRYFVL-FNSTLLYYKSKKDKKSYKPKGSIDLSGCTVREAPDPDS 63
PLN03192 PLN03192
Voltage-dependent potassium channel; Provisional
726-789 3.10e-04

Voltage-dependent potassium channel; Provisional


Pssm-ID: 215625 [Multi-domain]  Cd Length: 823  Bit Score: 44.47  E-value: 3.10e-04
                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|....
gi 564359681 726 LDTSVEDPQLRSPLHLAAELAHVVITQLLLWYGADVAARDAQGRTALFYARQAGSQLCADILLQ 789
Cdd:PLN03192 549 LDPDIGDSKGRTPLHIAASKGYEDCVLVLLKHACNVHIRDANGNTALWNAISAKHHKIFRILYH 612
Ank pfam00023
Ankyrin repeat; Ankyrins are multifunctional adaptors that link specific proteins to the ...
736-765 5.15e-04

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: 38.04  E-value: 5.15e-04
                          10        20        30
                  ....*....|....*....|....*....|.
gi 564359681  736 RSPLHLAAELA-HVVITQLLLWYGADVAARD 765
Cdd:pfam00023   3 NTPLHLAAGRRgNLEIVKLLLSKGADVNARD 33
PH_ORP9 cd13290
Human Oxysterol binding protein related protein 9 Pleckstrin homology (PH) domain; Human ORP9 ...
493-558 6.22e-04

Human Oxysterol binding protein related protein 9 Pleckstrin homology (PH) domain; Human ORP9 is proposed to function in regulation of Akt phosphorylation. ORP9 has 2 forms, a long (ORP9L) and a short (ORP9S). ORP9L contains an N-terminal PH domain, a FFAT motif (two phenylalanines in an acidic tract), and a C-terminal OSBP-related domain. ORP1S is truncated and contains a FFAT motif and an OSBP-related domain. Oxysterol binding proteins are a multigene family that is conserved in yeast, flies, worms, mammals and plants. In general OSBPs and ORPs have been found to be involved in the transport and metabolism of cholesterol and related lipids in eukaryotes. They all contain a C-terminal oxysterol binding domain, and most contain an N-terminal PH domain. OSBP PH domains bind to membrane phosphoinositides and thus likely play an important role in intracellular targeting. They are members of the oxysterol binding protein (OSBP) family which includes OSBP, OSBP-related proteins (ORP), Goodpasture antigen binding protein (GPBP), and Four phosphate adaptor protein 1 (FAPP1). They have a wide range of purported functions including sterol transport, cell cycle control, pollen development and vessicle transport from Golgi recognize both PI lipids and ARF proteins. PH domains have diverse functions, but in general are involved in targeting proteins to the appropriate cellular location or in the interaction with a binding partner. They share little sequence conservation, but all have a common fold, which is electrostatically polarized. Less than 10% of PH domains bind phosphoinositide phosphates (PIPs) with high affinity and specificity. PH domains are distinguished from other PIP-binding domains by their specific high-affinity binding to PIPs with two vicinal phosphate groups: PtdIns(3,4)P2, PtdIns(4,5)P2 or PtdIns(3,4,5)P3 which results in targeting some PH domain proteins to the plasma membrane. A few display strong specificity in lipid binding. Any specificity is usually determined by loop regions or insertions in the N-terminus of the domain, which are not conserved across all PH domains. PH domains are found in cellular signaling proteins such as serine/threonine kinase, tyrosine kinases, regulators of G-proteins, endocytotic GTPases, adaptors, as well as cytoskeletal associated molecules and in lipid associated enzymes.


Pssm-ID: 241444  Cd Length: 102  Bit Score: 39.74  E-value: 6.22e-04
                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 564359681 493 MVKKQRRKKLstpsKTEGSAVQAEEENFEFLIVSSTGQTWHFEAASFEERDAWVQAIESQILASLQ 558
Cdd:cd13290   38 MMRGSRRGCV----RLKGAVVGIDDEDDSTFTITVDQKTFHFQARDAEERERWIRALEDTILRHSQ 99
Roc pfam08477
Ras of Complex, Roc, domain of DAPkinase; Roc, or Ras of Complex, proteins are mitochondrial ...
72-167 8.19e-04

Ras of Complex, Roc, domain of DAPkinase; Roc, or Ras of Complex, proteins are mitochondrial Rho proteins (Miro-1, and Miro-2) and atypical Rho GTPases. Full-length proteins have a unique domain organization, with tandem GTP-binding domains and two EF hand domains (pfam00036) that may bind calcium. They are also larger than classical small GTPases. It has been proposed that they are involved in mitochondrial homeostasis and apoptosis.


Pssm-ID: 462490 [Multi-domain]  Cd Length: 114  Bit Score: 39.80  E-value: 8.19e-04
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564359681   72 RLGVLGDVRSGKSSLIHRFLTGSYqvlekpeSEQYKKEMLVDGQTHLVLIREEAGApDAKFSGW---------------- 135
Cdd:pfam08477   1 KVVLLGDSGVGKTSLLKRFVDDTF-------DPKYKSTIGVDFKTKTVLENDDNGK-KIKLNIWdtagqerfrslhpfyy 72
                          90       100       110
                  ....*....|....*....|....*....|....
gi 564359681  136 --ADAVIFVFsleDESSFQAVSHLHGQLISLRGE 167
Cdd:pfam08477  73 rgAAAALLVY---DSRTFSNLKYWLRELKKYAGN 103
Rab6 cd01861
Rab GTPase family 6 (Rab6); Rab6 is involved in microtubule-dependent transport pathways ...
76-229 1.56e-03

Rab GTPase family 6 (Rab6); Rab6 is involved in microtubule-dependent transport pathways through the Golgi and from endosomes to the Golgi. Rab6A of mammals is implicated in retrograde transport through the Golgi stack, and is also required for a slow, COPI-independent, retrograde transport pathway from the Golgi to the endoplasmic reticulum (ER). This pathway may allow Golgi residents to be recycled through the ER for scrutiny by ER quality-control systems. Yeast Ypt6p, the homolog of the mammalian Rab6 GTPase, is not essential for cell viability. Ypt6p acts in endosome-to-Golgi, in intra-Golgi retrograde transport, and possibly also in Golgi-to-ER trafficking. GTPase activating proteins (GAPs) interact with GTP-bound Rab and accelerate the hydrolysis of GTP to GDP. Guanine nucleotide exchange factors (GEFs) interact with GDP-bound Rabs to promote the formation of the GTP-bound state. Rabs are further regulated by guanine nucleotide dissociation inhibitors (GDIs), which facilitate Rab recycling by masking C-terminal lipid binding and promoting cytosolic localization. Most Rab GTPases contain a lipid modification site at the C-terminus, with sequence motifs CC, CXC, or CCX. Lipid binding is essential for membrane attachment, a key feature of most Rab proteins. Due to the presence of truncated sequences in this CD, the lipid modification site is not available for annotation.


Pssm-ID: 206654 [Multi-domain]  Cd Length: 161  Bit Score: 39.91  E-value: 1.56e-03
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564359681  76 LGDVRSGKSSLIHRFLTGSYqvlekpeSEQYK---------KEMLVDGQTHLVLIREEAGapDAKFSGW-------ADAV 139
Cdd:cd01861    6 LGDQSVGKTSIITRFMYDTF-------DNQYQatigidflsKTMYVDDKTVRLQLWDTAG--QERFRSLipsyirdSSVA 76
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564359681 140 IFVFSLEDESSFQAVSHLHGQLISLRGEgrgGLALALVGtqDRISASSPRVVGDARARALcTDMKRCSYYETCATYGLNV 219
Cdd:cd01861   77 VVVYDITNRQSFDNTDKWIDDVRDERGN---DVIIVLVG--NKTDLSDKRQVSTEEGEKK-AKENNAMFIETSAKAGHNV 150
                        170
                 ....*....|
gi 564359681 220 DRVFQEVAQK 229
Cdd:cd01861  151 KQLFKKIAQA 160
Rab24 cd04118
Rab GTPase family 24 (Rab24); Rab24 is distinct from other Rabs in several ways. It exists ...
71-237 1.64e-03

Rab GTPase family 24 (Rab24); Rab24 is distinct from other Rabs in several ways. It exists primarily in the GTP-bound state, having a low intrinsic GTPase activity; it is not efficiently geranyl-geranylated at the C-terminus; it does not form a detectable complex with Rab GDP-dissociation inhibitors (GDIs); and it has recently been shown to undergo tyrosine phosphorylation when overexpressed in vitro. The specific function of Rab24 still remains unknown. It is found in a transport route between ER-cis-Golgi and late endocytic compartments. It is putatively involved in an autophagic pathway, possibly directing misfolded proteins in the ER to degradative pathways. GTPase activating proteins (GAPs) interact with GTP-bound Rab and accelerate the hydrolysis of GTP to GDP. Guanine nucleotide exchange factors (GEFs) interact with GDP-bound Rabs to promote the formation of the GTP-bound state. Rabs are further regulated by guanine nucleotide dissociation inhibitors (GDIs), which facilitate Rab recycling by masking C-terminal lipid binding and promoting cytosolic localization. Most Rab GTPases contain a lipid modification site at the C-terminus, with sequence motifs CC, CXC, or CCX. Lipid binding is essential for membrane attachment, a key feature of most Rab proteins.


Pssm-ID: 133318 [Multi-domain]  Cd Length: 193  Bit Score: 40.62  E-value: 1.64e-03
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564359681  71 LRLGVLGDVRSGKSSLI-----HRFLTGSYQvlEKPESEQYKKEMLVDGQTHLVLIREEAG-----APDAKFSGWADAVI 140
Cdd:cd04118    1 VKVVMLGKESVGKTSLVeryvhHRFLVGPYQ--NTIGAAFVAKRMVVGERVVTLGIWDTAGseryeAMSRIYYRGAKAAI 78
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564359681 141 FVFSLEDESSFQAVSHLHGQLISLRGEGRgglaLALVGTQ-DRISASSPRVVGDARARALCTDMKRCSYYETCATYGLNV 219
Cdd:cd04118   79 VCYDLTDSSSFERAKFWVKELQNLEEHCK----IYLCGTKsDLIEQDRSLRQVDFHDVQDFADEIKAQHFETSSKTGQNV 154
                        170
                 ....*....|....*...
gi 564359681 220 DRVFQEVAQKVVTLRKQQ 237
Cdd:cd04118  155 DELFQKVAEDFVSRANNQ 172
Rab18 cd01863
Rab GTPase family 18 (Rab18); Rab18 subfamily. Mammalian Rab18 is implicated in endocytic ...
71-230 6.20e-03

Rab GTPase family 18 (Rab18); Rab18 subfamily. Mammalian Rab18 is implicated in endocytic transport and is expressed most highly in polarized epithelial cells. However, trypanosomal Rab, TbRAB18, is upregulated in the BSF (Blood Stream Form) stage and localized predominantly to elements of the Golgi complex. In human and mouse cells, Rab18 has been identified in lipid droplets, organelles that store neutral lipids. GTPase activating proteins (GAPs) interact with GTP-bound Rab and accelerate the hydrolysis of GTP to GDP. Guanine nucleotide exchange factors (GEFs) interact with GDP-bound Rabs to promote the formation of the GTP-bound state. Rabs are further regulated by guanine nucleotide dissociation inhibitors (GDIs), which facilitate Rab recycling by masking C-terminal lipid binding and promoting cytosolic localization. Most Rab GTPases contain a lipid modification site at the C-terminus, with sequence motifs CC, CXC, or CCX. Lipid binding is essential for membrane attachment, a key feature of most Rab proteins. Due to the presence of truncated sequences in this CD, the lipid modification site is not available for annotation.


Pssm-ID: 206656 [Multi-domain]  Cd Length: 161  Bit Score: 38.45  E-value: 6.20e-03
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564359681  71 LRLGVLGDVRSGKSSLIHRFLTGSYqvlekpESEQ-------YK-KEMLVDGQTHLVLIREEAGAP-----DAKFSGWAD 137
Cdd:cd01863    1 LKILLIGDSGVGKSSLLLRFTDDTF------DEDLsstigvdFKvKTVTVDGKKVKLAIWDTAGQErfrtlTSSYYRGAQ 74
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564359681 138 AVIFVFSLEDESSFQAVSHLHGQLISLrgEGRGGLALALVGTQ-DRISASSPRVVGDARARalctdMKRCSYYETCATYG 216
Cdd:cd01863   75 GVILVYDVTRRDTFDNLDTWLNELDTY--STNPDAVKMLVGNKiDKENREVTREEGQKFAR-----KHNMLFIETSAKTR 147
                        170
                 ....*....|....
gi 564359681 217 LNVDRVFQEVAQKV 230
Cdd:cd01863  148 IGVQQAFEELVEKI 161
RabL2 cd04124
Rab GTPase-like family 2 (Rab-like2); RabL2 (Rab-like2) subfamily. RabL2s are novel Rab ...
71-231 6.21e-03

Rab GTPase-like family 2 (Rab-like2); RabL2 (Rab-like2) subfamily. RabL2s are novel Rab proteins identified recently which display features that are distinct from other Rabs, and have been termed Rab-like. RabL2 contains RabL2a and RabL2b, two very similar Rab proteins that share > 98% sequence identity in humans. RabL2b maps to the subtelomeric region of chromosome 22q13.3 and RabL2a maps to 2q13, a region that suggests it is also a subtelomeric gene. Both genes are believed to be expressed ubiquitously, suggesting that RabL2s are the first example of duplicated genes in human proximal subtelomeric regions that are both expressed actively. Like other Rab-like proteins, RabL2s lack a prenylation site at the C-terminus. The specific functions of RabL2a and RabL2b remain unknown. GTPase activating proteins (GAPs) interact with GTP-bound Rab and accelerate the hydrolysis of GTP to GDP. Guanine nucleotide exchange factors (GEFs) interact with GDP-bound Rabs to promote the formation of the GTP-bound state. Rabs are further regulated by guanine nucleotide dissociation inhibitors (GDIs), which facilitate Rab recycling by masking C-terminal lipid binding and promoting cytosolic localization.


Pssm-ID: 133324 [Multi-domain]  Cd Length: 161  Bit Score: 38.30  E-value: 6.21e-03
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564359681  71 LRLGVLGDVRSGKSSLIHRFLTGSY--QVLEKPESEQYKKEMLVDGQTHLVLIREEAGAP-----DAKFSGWADAVIFVF 143
Cdd:cd04124    1 VKIILLGDSAVGKSKLVERFLMDGYepQQLSTYALTLYKHNAKFEGKTILVDFWDTAGQErfqtmHASYYHKAHACILVF 80
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564359681 144 SLEDESSFQAVSHLHGQLISLRGEgrgglaLALVGTQDRISAsSPRVVGDARARALCTDMkrcSYYETCATYGLNVDRVF 223
Cdd:cd04124   81 DVTRKITYKNLSKWYEELREYRPE------IPCIVVANKIDL-DPSVTQKKFNFAEKHNL---PLYYVSAADGTNVVKLF 150

                 ....*...
gi 564359681 224 QEVAQKVV 231
Cdd:cd04124  151 QDAIKLAV 158
PH_OSBP_ORP4 cd13284
Human Oxysterol binding protein and OSBP-related protein 4 Pleckstrin homology (PH) domain; ...
517-550 8.13e-03

Human Oxysterol binding protein and OSBP-related protein 4 Pleckstrin homology (PH) domain; Human OSBP is proposed to function is sterol-dependent regulation of ERK dephosphorylation and sphingomyelin synthesis as well as modulation of insulin signaling and hepatic lipogenesis. It contains a N-terminal PH domain, a FFAT motif (two phenylalanines in an acidic tract), and a C-terminal OSBP-related domain. OSBPs and Osh1p PH domains specifically localize to the Golgi apparatus in a PtdIns4P-dependent manner. ORP4 is proposed to function in Vimentin-dependent sterol transport and/or signaling. Human ORP4 has 2 forms, a long (ORP4L) and a short (ORP4S). ORP4L contains a N-terminal PH domain, a FFAT motif (two phenylalanines in an acidic tract), and a C-terminal OSBP-related domain. ORP4S is truncated and contains only an OSBP-related domain. Oxysterol binding proteins are a multigene family that is conserved in yeast, flies, worms, mammals and plants. They all contain a C-terminal oxysterol binding domain, and most contain an N-terminal PH domain. OSBP PH domains bind to membrane phosphoinositides and thus likely play an important role in intracellular targeting. They are members of the oxysterol binding protein (OSBP) family which includes OSBP, OSBP-related proteins (ORP), Goodpasture antigen binding protein (GPBP), and Four phosphate adaptor protein 1 (FAPP1). They have a wide range of purported functions including sterol transport, cell cycle control, pollen development and vessicle transport from Golgi recognize both PI lipids and ARF proteins. PH domains have diverse functions, but in general are involved in targeting proteins to the appropriate cellular location or in the interaction with a binding partner. They share little sequence conservation, but all have a common fold, which is electrostatically polarized. Less than 10% of PH domains bind phosphoinositide phosphates (PIPs) with high affinity and specificity. PH domains are distinguished from other PIP-binding domains by their specific high-affinity binding to PIPs with two vicinal phosphate groups: PtdIns(3,4)P2, PtdIns(4,5)P2 or PtdIns(3,4,5)P3 which results in targeting some PH domain proteins to the plasma membrane. A few display strong specificity in lipid binding. Any specificity is usually determined by loop regions or insertions in the N-terminus of the domain, which are not conserved across all PH domains. PH domains are found in cellular signaling proteins such as serine/threonine kinase, tyrosine kinases, regulators of G-proteins, endocytotic GTPases, adaptors, as well as cytoskeletal associated molecules and in lipid associated enzymes.


Pssm-ID: 270101  Cd Length: 99  Bit Score: 36.59  E-value: 8.13e-03
                         10        20        30
                 ....*....|....*....|....*....|....
gi 564359681 517 EENFEFLIVSSTGQTWHFEAASFEERDAWVQAIE 550
Cdd:cd13284   54 EDSCNFVISNGGTQTFHLKASSEVERQRWVTALE 87
 
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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