NCBI Home Page NCBI Site Search page NCBI Guide that lists and describes the NCBI resources
Conserved domains on  [gi|2462612273|ref|XP_054213184|]
View 

arf-GAP with GTPase, ANK repeat and PH domain-containing protein 3 isoform X4 [Homo sapiens]

Protein Classification

Centaurin_gamma and ArfGap_AGAP3 domain-containing protein( domain architecture ID 12936421)

protein containing domains Centaurin_gamma, PH_AGAP, and ArfGap_AGAP3

Graphical summary

 Zoom to residue level

show extra options »

Show site features     Horizontal zoom: ×

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, ...
129-286 1.36e-110

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: 335.23  E-value: 1.36e-110
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462612273 129 LKVGIVGNLSSGKSALVHRYLTGTYVQEESPEGGRFKKEIVVDGQSYLLLIRDEGGPPELQFAAWVDAVVFVFSLEDEIS 208
Cdd:cd04103     1 LKLGIVGNLRSGKSALVHRYLTGSYVQLESPEGGRFKKEVLVDGQSHLLLIRDEGGAPDAQFAGWVDAVIFVFSLEDEAS 80
                          90       100       110       120       130       140       150
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 2462612273 209 FQTVYNYFLRLCSFRNASEVPMVLVGTQDAISAANPRVIDDSRARKLSTDLKRCTYYETCATYGLNVERVFQDVAQKV 286
Cdd:cd04103    81 FQTVYRLYHQLSSYRNISEIPLILVGTQDAISASNPRVIDDARARQLCADMKRCSYYETCATYGLNVERVFQEAAQKI 158
ArfGap_AGAP3 cd08855
ArfGAP with GTPase domain, ANK repeat and PH domain 3; The AGAP subfamily of ADP-ribosylation ...
606-714 2.12e-79

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: 251.51  E-value: 2.12e-79
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462612273 606 ALAVQAVRTVRGNSFCIDCDAPNPDWASLNLGALMCIECSGIHRHLGAHLSRVRSLDLDDWPPELLAVMTAMGNALANSV 685
Cdd:cd08855     2 ALAIQSIRNVRGNSFCIDCDAPNPDWASLNLGALMCIECSGIHRNLGTHLSRVRSLDLDDWPVELSMVMTAIGNAMANSV 81
                          90       100
                  ....*....|....*....|....*....
gi 2462612273 686 WEGALGGYSKPGPDACREEKERWIRAKYE 714
Cdd:cd08855    82 WEGALDGYSKPGPDSTREEKERWIRAKYE 110
PH_AGAP cd01250
Arf-GAP with GTPase, ANK repeat and PH domain-containing protein Pleckstrin homology (PH) ...
402-589 1.64e-59

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: 197.54  E-value: 1.64e-59
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462612273 402 RAIPIKQGILLKRSGKSLNKEWKKKYVTLCDNGLLTYHPSLHDYMQNIHGKEIDLLRTTVKVPGKRLPRATPATApgtsp 481
Cdd:cd01250     1 RAIPIKQGYLYKRSSKSLNKEWKKKYVTLCDDGRLTYHPSLHDYMENVHGKEIDLLRTTVKVPGKRPPRASSKSA----- 75
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462612273 482 ranglsversntqlgggtasgpaevlssspkldpppsphsnrkkhrrkkstgtprpdgpssateeaeesFEFVVVSLTGQ 561
Cdd:cd01250    76 ---------------------------------------------------------------------FEFIIVSLDGK 86
                         170       180
                  ....*....|....*....|....*...
gi 2462612273 562 TWHFEASTAEERELWVQSVQAQILASLQ 589
Cdd:cd01250    87 QWHFEAASSEERDEWVQAIEQQILASLQ 114
ANKYR COG0666
Ankyrin repeat [Signal transduction mechanisms];
733-822 2.33e-11

Ankyrin repeat [Signal transduction mechanisms];


:

Pssm-ID: 440430 [Multi-domain]  Cd Length: 289  Bit Score: 65.36  E-value: 2.33e-11
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462612273 733 LLRAVVEDDLRLLVMLLAHGskEEVNETygDGDGRTALHLSSAMANVVFTQLLIWYGVDVRSRDARGLTPLAYARRAGSQ 812
Cdd:COG0666    91 LHAAARNGDLEIVKLLLEAG--ADVNAR--DKDGETPLHLAAYNGNLEIVKLLLEAGADVNAQDNDGNTPLHLAAANGNL 166
                          90
                  ....*....|
gi 2462612273 813 ECADILIQHG 822
Cdd:COG0666   167 EIVKLLLEAG 176
 
Name Accession Description Interval E-value
Centaurin_gamma cd04103
Centaurin gamma (CENTG) GTPase; The centaurins (alpha, beta, gamma, and delta) are large, ...
129-286 1.36e-110

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: 335.23  E-value: 1.36e-110
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462612273 129 LKVGIVGNLSSGKSALVHRYLTGTYVQEESPEGGRFKKEIVVDGQSYLLLIRDEGGPPELQFAAWVDAVVFVFSLEDEIS 208
Cdd:cd04103     1 LKLGIVGNLRSGKSALVHRYLTGSYVQLESPEGGRFKKEVLVDGQSHLLLIRDEGGAPDAQFAGWVDAVIFVFSLEDEAS 80
                          90       100       110       120       130       140       150
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 2462612273 209 FQTVYNYFLRLCSFRNASEVPMVLVGTQDAISAANPRVIDDSRARKLSTDLKRCTYYETCATYGLNVERVFQDVAQKV 286
Cdd:cd04103    81 FQTVYRLYHQLSSYRNISEIPLILVGTQDAISASNPRVIDDARARQLCADMKRCSYYETCATYGLNVERVFQEAAQKI 158
ArfGap_AGAP3 cd08855
ArfGAP with GTPase domain, ANK repeat and PH domain 3; The AGAP subfamily of ADP-ribosylation ...
606-714 2.12e-79

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: 251.51  E-value: 2.12e-79
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462612273 606 ALAVQAVRTVRGNSFCIDCDAPNPDWASLNLGALMCIECSGIHRHLGAHLSRVRSLDLDDWPPELLAVMTAMGNALANSV 685
Cdd:cd08855     2 ALAIQSIRNVRGNSFCIDCDAPNPDWASLNLGALMCIECSGIHRNLGTHLSRVRSLDLDDWPVELSMVMTAIGNAMANSV 81
                          90       100
                  ....*....|....*....|....*....
gi 2462612273 686 WEGALGGYSKPGPDACREEKERWIRAKYE 714
Cdd:cd08855    82 WEGALDGYSKPGPDSTREEKERWIRAKYE 110
PH_AGAP cd01250
Arf-GAP with GTPase, ANK repeat and PH domain-containing protein Pleckstrin homology (PH) ...
402-589 1.64e-59

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: 197.54  E-value: 1.64e-59
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462612273 402 RAIPIKQGILLKRSGKSLNKEWKKKYVTLCDNGLLTYHPSLHDYMQNIHGKEIDLLRTTVKVPGKRLPRATPATApgtsp 481
Cdd:cd01250     1 RAIPIKQGYLYKRSSKSLNKEWKKKYVTLCDDGRLTYHPSLHDYMENVHGKEIDLLRTTVKVPGKRPPRASSKSA----- 75
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462612273 482 ranglsversntqlgggtasgpaevlssspkldpppsphsnrkkhrrkkstgtprpdgpssateeaeesFEFVVVSLTGQ 561
Cdd:cd01250    76 ---------------------------------------------------------------------FEFIIVSLDGK 86
                         170       180
                  ....*....|....*....|....*...
gi 2462612273 562 TWHFEASTAEERELWVQSVQAQILASLQ 589
Cdd:cd01250    87 QWHFEAASSEERDEWVQAIEQQILASLQ 114
ArfGap pfam01412
Putative GTPase activating protein for Arf; Putative zinc fingers with GTPase activating ...
608-721 9.67e-50

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: 170.87  E-value: 9.67e-50
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462612273 608 AVQAVRTVRGNSFCIDCDAPNPDWASLNLGALMCIECSGIHRHLGAHLSRVRSLDLDDWPPELLAVMTAMGNALANSVWE 687
Cdd:pfam01412   3 VLRELLKLPGNKVCADCGAPNPTWASVNLGIFICIDCSGVHRSLGVHISKVRSLTLDTWTDEQLELMKAGGNDRANEFWE 82
                          90       100       110
                  ....*....|....*....|....*....|....
gi 2462612273 688 GALGGYSKPGPDACREEKERWIRAKYEQKLFLAP 721
Cdd:pfam01412  83 ANLPPSYKPPPSSDREKRESFIRAKYVEKKFAKP 116
ArfGap smart00105
Putative GTP-ase activating proteins for the small GTPase, ARF; Putative zinc fingers with ...
610-726 6.10e-48

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: 165.98  E-value: 6.10e-48
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462612273  610 QAVRTVRGNSFCIDCDAPNPDWASLNLGALMCIECSGIHRHLGAHLSRVRSLDLDDWPPELLAVMTAMGNALANSVWEGA 689
Cdd:smart00105   2 KLLRSIPGNKKCFDCGAPNPTWASVNLGVFLCIECSGIHRSLGVHISKVRSLTLDTWTEEELRLLQKGGNENANSIWESN 81
                           90       100       110
                   ....*....|....*....|....*....|....*...
gi 2462612273  690 LG-GYSKPGPDACREEKERWIRAKYEQKLFLAPLPSSD 726
Cdd:smart00105  82 LDdFSLKPPDDDDQQKYESFIAAKYEEKLFVPPESAEE 119
COG5347 COG5347
GTPase-activating protein that regulates ARFs (ADP-ribosylation factors), involved in ...
601-785 6.66e-29

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: 117.96  E-value: 6.66e-29
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462612273 601 GNQNAALAVQAVRTVRGNSFCIDCDAPNPDWASLNLGALMCIECSGIHRHLGAHLSRVRSLDLDDWPPELLAVMTAMGNA 680
Cdd:COG5347     3 TKSEDRKLLKLLKSDSSNKKCADCGAPNPTWASVNLGVFLCIDCAGVHRSLGVHISKVKSLTLDNWTEEELRRMEVGGNS 82
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462612273 681 LANSVWEG----ALGGYSKPGPDAcrEEKERWIRAKYEQKLFL----APLPSSDVPLGQQLLRAVVEDDLRLL-----VM 747
Cdd:COG5347    83 NANRFYEKnlldQLLLPIKAKYDS--SVAKKYIRKKYELKKFIddssSPSDFSSFSASSTRTVDSVDDRLDSEsqsrsSS 160
                         170       180       190       200
                  ....*....|....*....|....*....|....*....|....
gi 2462612273 748 LLAHGSKEEVNETYGDGDGRTALHL------SSAMANVVFTQLL 785
Cdd:COG5347   161 ASLGNSNRPDDELNVESFQSTGSKPrsltstKSNKDNLLNSELL 204
PLN03114 PLN03114
ADP-ribosylation factor GTPase-activating protein AGD10; Provisional
602-730 1.53e-17

ADP-ribosylation factor GTPase-activating protein AGD10; Provisional


Pssm-ID: 178661 [Multi-domain]  Cd Length: 395  Bit Score: 85.68  E-value: 1.53e-17
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462612273 602 NQNAALAV-QAVRTVRGNSFCIDCDAPNPDWASLNLGALMCIECSGIHRHLGAHLSRVRSLDLDDWPPELLAVMTAMGNA 680
Cdd:PLN03114    5 NLNDKISVfKKLKAKSDNKICFDCNAKNPTWASVTYGIFLCIDCSAVHRSLGVHISFVRSTNLDSWSSEQLKMMIYGGNN 84
                          90       100       110       120       130       140
                  ....*....|....*....|....*....|....*....|....*....|....*....|.
gi 2462612273 681 LANSVWEG---ALGG-----YSKPGPDACREEKERWI-RAKYEQKLFLAPLP--SSDVPLG 730
Cdd:PLN03114   85 RAQVFFKQygwSDGGkteakYTSRAADLYKQILAKEVaKSKAEEELDLPPSPpdSTQVPNG 145
small_GTPase smart00010
Small GTPase of the Ras superfamily; ill-defined subfamily; SMART predicts Ras-like small ...
127-292 5.18e-17

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: 79.14  E-value: 5.18e-17
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462612273  127 PELKVGIVGNLSSGKSALVHRYLTGTYVQEESP--EGGrFKKEIVVDGQSYLLLIRDEGGppELQFAAWVD-------AV 197
Cdd:smart00010   1 REYKLVVLGGGGVGKSALTIQFVQGHFVDEYDPtiEDS-YRKQIEIDGEVCLLDILDTAG--QEEFSAMRDqymrtgeGF 77
                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462612273  198 VFVFSLEDEISFQTVYNYFLRLCSFRNASEVPMVLVGTQ-DAIsaaNPRVIDDSRARKLSTDLKrCTYYETCATYGLNVE 276
Cdd:smart00010  78 LLVYSITDRQSFEEIAKFREQILRVKDRDDVPIVLVGNKcDLE---NERVVSTEEGKELARQWG-CPFLETSAKERINVD 153
                          170
                   ....*....|....*.
gi 2462612273  277 RVFQDVaqkVVALRKK 292
Cdd:smart00010 154 EAFYDL---VREIRKS 166
Ras pfam00071
Ras family; Includes sub-families Ras, Rab, Rac, Ral, Ran, Rap Ypt1 and more. Shares P-loop ...
130-286 9.70e-16

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: 75.63  E-value: 9.70e-16
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462612273 130 KVGIVGNLSSGKSALVHRYLTGTYVQE-ESPEGGRFK-KEIVVDGQSYLLLIRDEGGPPElqFAA-----WVDAVVF--V 200
Cdd:pfam00071   1 KLVLVGDGGVGKSSLLIRFTQNKFPEEyIPTIGVDFYtKTIEVDGKTVKLQIWDTAGQER--FRAlrplyYRGADGFllV 78
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462612273 201 FSLEDEISFQTVYNYF---LRLCSfrnaSEVPMVLVGTQdaISAANPRVIDDSRARKLSTDLKrCTYYETCATYGLNVER 277
Cdd:pfam00071  79 YDITSRDSFENVKKWVeeiLRHAD----ENVPIVLVGNK--CDLEDQRVVSTEEGEALAKELG-LPFMETSAKTNENVEE 151

                  ....*....
gi 2462612273 278 VFQDVAQKV 286
Cdd:pfam00071 152 AFEELAREI 160
Gem1 COG1100
GTPase SAR1 family domain [General function prediction only];
128-284 8.89e-12

GTPase SAR1 family domain [General function prediction only];


Pssm-ID: 440717 [Multi-domain]  Cd Length: 177  Bit Score: 64.62  E-value: 8.89e-12
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462612273 128 ELKVGIVGNLSSGKSALVHRYLTGTYVQEE--SPEG-GRFKKEIVVDGQSYLLLIRDEGGPPEL-----QFAAWV---DA 196
Cdd:COG1100     3 EKKIVVVGTGGVGKTSLVNRLVGDIFSLEKylSTNGvTIDKKELKLDGLDVDLVIWDTPGQDEFretrqFYARQLtgaSL 82
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462612273 197 VVFVFSLEDEISFQTVYNYFLRLcsFRNASEVPMVLVGTQ-DAISaaNPRVIDDSRARKLSTDLKRCTYYETCATYGLNV 275
Cdd:COG1100    83 YLFVVDGTREETLQSLYELLESL--RRLGKKSPIILVLNKiDLYD--EEEIEDEERLKEALSEDNIVEVVATSAKTGEGV 158

                  ....*....
gi 2462612273 276 ERVFQDVAQ 284
Cdd:COG1100   159 EELFAALAE 167
ANKYR COG0666
Ankyrin repeat [Signal transduction mechanisms];
733-822 2.33e-11

Ankyrin repeat [Signal transduction mechanisms];


Pssm-ID: 440430 [Multi-domain]  Cd Length: 289  Bit Score: 65.36  E-value: 2.33e-11
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462612273 733 LLRAVVEDDLRLLVMLLAHGskEEVNETygDGDGRTALHLSSAMANVVFTQLLIWYGVDVRSRDARGLTPLAYARRAGSQ 812
Cdd:COG0666    91 LHAAARNGDLEIVKLLLEAG--ADVNAR--DKDGETPLHLAAYNGNLEIVKLLLEAGADVNAQDNDGNTPLHLAAANGNL 166
                          90
                  ....*....|
gi 2462612273 813 ECADILIQHG 822
Cdd:COG0666   167 EIVKLLLEAG 176
Ank_2 pfam12796
Ankyrin repeats (3 copies);
733-823 3.58e-09

Ankyrin repeats (3 copies);


Pssm-ID: 463710 [Multi-domain]  Cd Length: 91  Bit Score: 54.35  E-value: 3.58e-09
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462612273 733 LLRAVVEDDLRLLVMLLAHGSKEEVNetygDGDGRTALHLSSAMANVVFTQLLIWYgVDVRSRDaRGLTPLAYARRAGSQ 812
Cdd:pfam12796   1 LHLAAKNGNLELVKLLLENGADANLQ----DKNGRTALHLAAKNGHLEIVKLLLEH-ADVNLKD-NGRTALHYAARSGHL 74
                          90
                  ....*....|.
gi 2462612273 813 ECADILIQHGC 823
Cdd:pfam12796  75 EIVKLLLEKGA 85
PTZ00369 PTZ00369
Ras-like protein; Provisional
128-286 5.14e-08

Ras-like protein; Provisional


Pssm-ID: 240385 [Multi-domain]  Cd Length: 189  Bit Score: 53.71  E-value: 5.14e-08
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462612273 128 ELKVGIVGNLSSGKSALVHRYLTGTYVQEESPE-GGRFKKEIVVDGQSYLLLIRDEGGPPEL-----QFAAWVDAVVFVF 201
Cdd:PTZ00369    5 EYKLVVVGGGGVGKSALTIQFIQNHFIDEYDPTiEDSYRKQCVIDEETCLLDILDTAGQEEYsamrdQYMRTGQGFLCVY 84
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462612273 202 SLEDEISFQTVYNYFLRLCSFRNASEVPMVLVGTQDAISaaNPRVIDDSRARKLSTDLKrCTYYETCATYGLNVERVFQD 281
Cdd:PTZ00369   85 SITSRSSFEEIASFREQILRVKDKDRVPMILVGNKCDLD--SERQVSTGEGQELAKSFG-IPFLETSAKQRVNVDEAFYE 161

                  ....*
gi 2462612273 282 VAQKV 286
Cdd:PTZ00369  162 LVREI 166
PH smart00233
Pleckstrin homology domain; Domain commonly found in eukaryotic signalling proteins. The ...
405-584 2.07e-06

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: 47.16  E-value: 2.07e-06
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462612273  405 PIKQGILLKRSGKSlNKEWKKKYVTLCdNGLLTYHPSLHDYMQNIHGKEIDLLRTTVKVPgkrlpratpatapgtspran 484
Cdd:smart00233   1 VIKEGWLYKKSGGG-KKSWKKRYFVLF-NSTLLYYKSKKDKKSYKPKGSIDLSGCTVREA-------------------- 58
                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462612273  485 glsversntqlgggtasgpaevlsssPKLDPPPSPHSnrkkhrrkkstgtprpdgpssateeaeesfeFVVVSLTGQTWH 564
Cdd:smart00233  59 --------------------------PDPDSSKKPHC-------------------------------FEIKTSDRKTLL 81
                          170       180
                   ....*....|....*....|
gi 2462612273  565 FEASTAEERELWVQSVQAQI 584
Cdd:smart00233  82 LQAESEEEREKWVEALRKAI 101
PTZ00322 PTZ00322
6-phosphofructo-2-kinase/fructose-2,6-biphosphatase; Provisional
763-844 2.48e-05

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


Pssm-ID: 140343 [Multi-domain]  Cd Length: 664  Bit Score: 47.97  E-value: 2.48e-05
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462612273 763 DGDGRTALHLSSAMANVVFTQLLIWYGVDVRSRDARGLTPLAYARRAGSQECADILIQH----------GCPGEGCGLAP 832
Cdd:PTZ00322  112 DYDGRTPLHIACANGHVQVVRVLLEFGADPTLLDKDGKTPLELAEENGFREVVQLLSRHsqchfelganAKPDSFTGKPP 191
                          90
                  ....*....|..
gi 2462612273 833 TPNREPANGTNP 844
Cdd:PTZ00322  192 SLEDSPISSHHP 203
TRPV5-6 cd22192
Transient Receptor Potential channel, Vanilloid subfamily (TRPV), types 5 and 6; TRPV5 and ...
723-822 1.13e-03

Transient Receptor Potential channel, Vanilloid subfamily (TRPV), types 5 and 6; TRPV5 and TRPV6 (TRPV5/6) are two homologous members within the vanilloid subfamily of the transient receptor potential (TRP) family. TRPV5 and TRPV6 show only 30-40% homology with other members of the TRP family and have unique properties that differentiates them from other TRP channels. They mediate calcium uptake in epithelia and their expression is dramatically increased in numerous types of cancer. The structure of TRPV5/6 shows the typical topology features of all TRP family members, such as six transmembrane regions, a short hydrophobic stretch between transmembrane segments 5 and 6, which is predicted to form the Ca2+ pore, and large intracellular N- and C-terminal domains. The N-terminal domain of TRPV5/6 contains three ankyrin repeats. This structural element is present in several proteins and plays a role in protein-protein interactions. The N- and C-terminal tails of TRPV5/6 each contain an internal PDZ motif which can function as part of a molecular scaffold via interaction with PDZ-domain containing proteins. A major difference between the properties of TRPV5 and TRPV6 is in their tissue distribution: TRPV5 is predominantly expressed in the distal convoluted tubules (DCT) and connecting tubules (CNT) of the kidney, with limited expression in extrarenal tissues. In contrast, TRPV6 has a broader expression pattern such as expression in the intestine, kidney, placenta, epididymis, exocrine tissues, and a few other tissues.


Pssm-ID: 411976 [Multi-domain]  Cd Length: 609  Bit Score: 42.69  E-value: 1.13e-03
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462612273 723 PSSDV----PLGQQLLRAVVEDDLRLLVMLLAHGSKEEVNE--TYGDGDGRTALHLSSAMANVVFTQLLIWYGVDVRSRD 796
Cdd:cd22192    40 PSCDLfqrgALGETALHVAALYDNLEAAVVLMEAAPELVNEpmTSDLYQGETALHIAVVNQNLNLVRELIARGADVVSPR 119
                          90       100       110       120
                  ....*....|....*....|....*....|....*....|
gi 2462612273 797 ARGLT--------------PLAYARRAGSQECADILIQHG 822
Cdd:cd22192   120 ATGTFfrpgpknliyygehPLSFAACVGNEEIVRLLIEHG 159
PH pfam00169
PH domain; PH stands for pleckstrin homology.
405-584 2.07e-03

PH domain; PH stands for pleckstrin homology.


Pssm-ID: 459697 [Multi-domain]  Cd Length: 105  Bit Score: 38.70  E-value: 2.07e-03
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462612273 405 PIKQGILLKRSGKsLNKEWKKKYVTLCDNGLLTYHPSLHDYMQNIHGKeIDLLRTTVKvpgkrlpratpatapgtspran 484
Cdd:pfam00169   1 VVKEGWLLKKGGG-KKKSWKKRYFVLFDGSLLYYKDDKSGKSKEPKGS-ISLSGCEVV---------------------- 56
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462612273 485 glsversntqlgggtasgpaevlssspklDPPPSPHSNRKKHrrkkstgtprpdgpssateeaeesFEFVVVSLTG-QTW 563
Cdd:pfam00169  57 -----------------------------EVVASDSPKRKFC------------------------FELRTGERTGkRTY 83
                         170       180
                  ....*....|....*....|.
gi 2462612273 564 HFEASTAEERELWVQSVQAQI 584
Cdd:pfam00169  84 LLQAESEEERKDWIKAIQSAI 104
 
Name Accession Description Interval E-value
Centaurin_gamma cd04103
Centaurin gamma (CENTG) GTPase; The centaurins (alpha, beta, gamma, and delta) are large, ...
129-286 1.36e-110

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: 335.23  E-value: 1.36e-110
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462612273 129 LKVGIVGNLSSGKSALVHRYLTGTYVQEESPEGGRFKKEIVVDGQSYLLLIRDEGGPPELQFAAWVDAVVFVFSLEDEIS 208
Cdd:cd04103     1 LKLGIVGNLRSGKSALVHRYLTGSYVQLESPEGGRFKKEVLVDGQSHLLLIRDEGGAPDAQFAGWVDAVIFVFSLEDEAS 80
                          90       100       110       120       130       140       150
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 2462612273 209 FQTVYNYFLRLCSFRNASEVPMVLVGTQDAISAANPRVIDDSRARKLSTDLKRCTYYETCATYGLNVERVFQDVAQKV 286
Cdd:cd04103    81 FQTVYRLYHQLSSYRNISEIPLILVGTQDAISASNPRVIDDARARQLCADMKRCSYYETCATYGLNVERVFQEAAQKI 158
ArfGap_AGAP3 cd08855
ArfGAP with GTPase domain, ANK repeat and PH domain 3; The AGAP subfamily of ADP-ribosylation ...
606-714 2.12e-79

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: 251.51  E-value: 2.12e-79
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462612273 606 ALAVQAVRTVRGNSFCIDCDAPNPDWASLNLGALMCIECSGIHRHLGAHLSRVRSLDLDDWPPELLAVMTAMGNALANSV 685
Cdd:cd08855     2 ALAIQSIRNVRGNSFCIDCDAPNPDWASLNLGALMCIECSGIHRNLGTHLSRVRSLDLDDWPVELSMVMTAIGNAMANSV 81
                          90       100
                  ....*....|....*....|....*....
gi 2462612273 686 WEGALGGYSKPGPDACREEKERWIRAKYE 714
Cdd:cd08855    82 WEGALDGYSKPGPDSTREEKERWIRAKYE 110
ArfGap_AGAP cd08836
ArfGAP with GTPase domain, ANK repeat and PH domains; The AGAP subfamily of ADP-ribosylation ...
608-714 5.44e-78

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: 247.59  E-value: 5.44e-78
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462612273 608 AVQAVRTVRGNSFCIDCDAPNPDWASLNLGALMCIECSGIHRHLGAHLSRVRSLDLDDWPPELLAVMTAMGNALANSVWE 687
Cdd:cd08836     2 ALQAIRNVRGNDHCVDCGAPNPDWASLNLGALMCIECSGIHRNLGTHISRVRSLDLDDWPVELLKVMSAIGNDLANSVWE 81
                          90       100
                  ....*....|....*....|....*..
gi 2462612273 688 GALGGYSKPGPDACREEKERWIRAKYE 714
Cdd:cd08836    82 GNTQGRTKPTPDSSREEKERWIRAKYE 108
ArfGap_AGAP2 cd08853
ArfGAP with GTPase domain, ANK repeat and PH domain 2; The AGAP subfamily of ADP-ribosylation ...
606-714 3.62e-62

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: 204.86  E-value: 3.62e-62
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462612273 606 ALAVQAVRTVRGNSFCIDCDAPNPDWASLNLGALMCIECSGIHRHLGAHLSRVRSLDLDDWPPELLAVMTAMGNALANSV 685
Cdd:cd08853     1 AMALQSIRNMRGNSHCVDCETQNPKWASLNLGVLMCIECSGIHRNLGTHLSRVRSLDLDDWPVELRKVMSSIGNELANSI 80
                          90       100
                  ....*....|....*....|....*....
gi 2462612273 686 WEGALGGYSKPGPDACREEKERWIRAKYE 714
Cdd:cd08853    81 WEGSSQGQTKPSSDSTREEKERWIRAKYE 109
PH_AGAP cd01250
Arf-GAP with GTPase, ANK repeat and PH domain-containing protein Pleckstrin homology (PH) ...
402-589 1.64e-59

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: 197.54  E-value: 1.64e-59
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462612273 402 RAIPIKQGILLKRSGKSLNKEWKKKYVTLCDNGLLTYHPSLHDYMQNIHGKEIDLLRTTVKVPGKRLPRATPATApgtsp 481
Cdd:cd01250     1 RAIPIKQGYLYKRSSKSLNKEWKKKYVTLCDDGRLTYHPSLHDYMENVHGKEIDLLRTTVKVPGKRPPRASSKSA----- 75
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462612273 482 ranglsversntqlgggtasgpaevlssspkldpppsphsnrkkhrrkkstgtprpdgpssateeaeesFEFVVVSLTGQ 561
Cdd:cd01250    76 ---------------------------------------------------------------------FEFIIVSLDGK 86
                         170       180
                  ....*....|....*....|....*...
gi 2462612273 562 TWHFEASTAEERELWVQSVQAQILASLQ 589
Cdd:cd01250    87 QWHFEAASSEERDEWVQAIEQQILASLQ 114
ArfGap_AGAP1 cd08854
ArfGAP with GTPase domain, ANK repeat and PH domain 1; The AGAP subfamily of ADP-ribosylation ...
606-714 2.50e-58

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: 194.46  E-value: 2.50e-58
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462612273 606 ALAVQAVRTVRGNSFCIDCDAPNPDWASLNLGALMCIECSGIHRHLGAHLSRVRSLDLDDWPPELLAVMTAMGNALANSV 685
Cdd:cd08854     1 AVAIQAIRNAKGNSLCVDCGAPNPTWASLNLGALICIECSGIHRNLGTHLSRVRSLDLDDWPRELTLVLTAIGNHMANSI 80
                          90       100
                  ....*....|....*....|....*....
gi 2462612273 686 WEGALGGYSKPGPDACREEKERWIRAKYE 714
Cdd:cd08854    81 WESCTQGRTKPAPDSSREERESWIRAKYE 109
ArfGap cd08204
GTPase-activating protein (GAP) for the ADP ribosylation factors (ARFs); ArfGAPs are a family ...
609-713 2.10e-53

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: 180.39  E-value: 2.10e-53
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462612273 609 VQAVRTVRGNSFCIDCDAPNPDWASLNLGALMCIECSGIHRHLGAHLSRVRSLDLDDWPPELLAVMTAMGNALANSVWEG 688
Cdd:cd08204     1 LEELLKLPGNKVCADCGAPDPRWASINLGVFICIRCSGIHRSLGVHISKVRSLTLDSWTPEQVELMKAIGNARANAYYEA 80
                          90       100
                  ....*....|....*....|....*.
gi 2462612273 689 ALG-GYSKPGPDACREEKERWIRAKY 713
Cdd:cd08204    81 NLPpGFKKPTPDSSDEEREQFIRAKY 106
ArfGap pfam01412
Putative GTPase activating protein for Arf; Putative zinc fingers with GTPase activating ...
608-721 9.67e-50

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: 170.87  E-value: 9.67e-50
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462612273 608 AVQAVRTVRGNSFCIDCDAPNPDWASLNLGALMCIECSGIHRHLGAHLSRVRSLDLDDWPPELLAVMTAMGNALANSVWE 687
Cdd:pfam01412   3 VLRELLKLPGNKVCADCGAPNPTWASVNLGIFICIDCSGVHRSLGVHISKVRSLTLDTWTDEQLELMKAGGNDRANEFWE 82
                          90       100       110
                  ....*....|....*....|....*....|....
gi 2462612273 688 GALGGYSKPGPDACREEKERWIRAKYEQKLFLAP 721
Cdd:pfam01412  83 ANLPPSYKPPPSSDREKRESFIRAKYVEKKFAKP 116
ArfGap smart00105
Putative GTP-ase activating proteins for the small GTPase, ARF; Putative zinc fingers with ...
610-726 6.10e-48

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: 165.98  E-value: 6.10e-48
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462612273  610 QAVRTVRGNSFCIDCDAPNPDWASLNLGALMCIECSGIHRHLGAHLSRVRSLDLDDWPPELLAVMTAMGNALANSVWEGA 689
Cdd:smart00105   2 KLLRSIPGNKKCFDCGAPNPTWASVNLGVFLCIECSGIHRSLGVHISKVRSLTLDTWTEEELRLLQKGGNENANSIWESN 81
                           90       100       110
                   ....*....|....*....|....*....|....*...
gi 2462612273  690 LG-GYSKPGPDACREEKERWIRAKYEQKLFLAPLPSSD 726
Cdd:smart00105  82 LDdFSLKPPDDDDQQKYESFIAAKYEEKLFVPPESAEE 119
ArfGap_ACAP cd08835
ArfGAP domain of ACAP (ArfGAP with Coiled-coil, ANK repeat and PH domains) proteins; ArfGAP ...
608-719 1.63e-45

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: 158.96  E-value: 1.63e-45
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462612273 608 AVQAVRTVRGNSFCIDCDAPNPDWASLNLGALMCIECSGIHRHLGAHLSRVRSLDLDDWPPELLAVMTAMGNALANSVWE 687
Cdd:cd08835     3 ALEQVLSVPGNAQCCDCGSPDPRWASINLGVTLCIECSGIHRSLGVHVSKVRSLTLDSWEPELLKVMLELGNDVVNRIYE 82
                          90       100       110
                  ....*....|....*....|....*....|....
gi 2462612273 688 GALGGYS--KPGPDACREEKERWIRAKYEQKLFL 719
Cdd:cd08835    83 ANVPDDGsvKPTPDSSRQEREAWIRAKYVEKKFV 116
ArfGap_ACAP3 cd08850
ArfGAP domain of ACAP3 (ArfGAP with Coiled-coil, ANK repeat and PH domains 3); ACAP3 belongs ...
609-719 2.33e-43

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: 152.79  E-value: 2.33e-43
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462612273 609 VQAVRTVRGNSFCIDCDAPNPDWASLNLGALMCIECSGIHRHLGAHLSRVRSLDLDDWPPELLAVMTAMGNALANSVWEG 688
Cdd:cd08850     4 LQRVQSIAGNDQCCDCGQPDPRWASINLGILLCIECSGIHRSLGVHCSKVRSLTLDSWEPELLKLMCELGNSTVNQIYEA 83
                          90       100       110
                  ....*....|....*....|....*....|...
gi 2462612273 689 AL--GGYSKPGPDACREEKERWIRAKYEQKLFL 719
Cdd:cd08850    84 QCeeLGLKKPTASSSRQDKEAWIKAKYVEKKFL 116
ArfGap_ACAP1 cd08852
ArfGAP domain of ACAP1 (ArfGAP with Coiled-coil, ANK repeat and PH domains 1); ACAP1 belongs ...
608-723 2.03e-41

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: 147.41  E-value: 2.03e-41
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462612273 608 AVQAVRTVRGNSFCIDCDAPNPDWASLNLGALMCIECSGIHRHLGAHLSRVRSLDLDDWPPELLAVMTAMGNALANSVWE 687
Cdd:cd08852     3 AVAQVQSVDGNAQCCDCREPAPEWASINLGVTLCIQCSGIHRSLGVHFSKVRSLTLDSWEPELVKLMCELGNVIINQIYE 82
                          90       100       110
                  ....*....|....*....|....*....|....*...
gi 2462612273 688 GALGGYS--KPGPDACREEKERWIRAKYEQKLFLAPLP 723
Cdd:cd08852    83 ARIEAMAikKPGPSSSRQEKEAWIRAKYVEKKFITKLP 120
ArfGap_ACAP2 cd08851
ArfGAP domain of ACAP2 (ArfGAP with Coiled-coil, ANK repeat and PH domains 2); ACAP2 belongs ...
608-719 5.48e-39

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: 140.51  E-value: 5.48e-39
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462612273 608 AVQAVRTVRGNSFCIDCDAPNPDWASLNLGALMCIECSGIHRHLGAHLSRVRSLDLDDWPPELLAVMTAMGNALANSVWE 687
Cdd:cd08851     3 ALQRVQCIPGNASCCDCGLADPRWASINLGITLCIECSGIHRSLGVHFSKVRSLTLDTWEPELLKLMCELGNDVINRIYE 82
                          90       100       110
                  ....*....|....*....|....*....|....
gi 2462612273 688 GALG--GYSKPGPDACREEKERWIRAKYEQKLFL 719
Cdd:cd08851    83 ARVEkmGAKKPQPGGQRQEKEAYIRAKYVERKFV 116
ArfGap_ADAP cd08832
ArfGap with dual PH domains; The ADAP subfamily, ArfGAPs with dual pleckstrin homology (PH) ...
617-713 1.60e-38

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: 138.93  E-value: 1.60e-38
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462612273 617 GNSFCIDCDAPNPDWASLNLGALMCIECSGIHRHLGAHLSRVRSLDLDDWPPELLAVMTAMGNALANSVWEGAL-GGYSK 695
Cdd:cd08832    16 GNNTCADCGAPDPEWASYNLGVFICLDCSGIHRSLGTHISKVKSLRLDNWDDSQVEFMEENGNEKAKAKYEAHVpAFYRR 95
                          90
                  ....*....|....*...
gi 2462612273 696 PGPDACREEKERWIRAKY 713
Cdd:cd08832    96 PTPTDPQVLREQWIRAKY 113
ArfGap_ASAP cd08834
ArfGAP domain of ASAP (Arf GAP, SH3, ANK repeat and PH domains) subfamily of ADP-ribosylation ...
609-718 3.47e-38

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: 138.12  E-value: 3.47e-38
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462612273 609 VQAVRTVRGNSFCIDCDAPNPDWASLNLGALMCIECSGIHRHLGAHLSRVRSLDLDDWPPELLAVMTAMGNALANSVWEG 688
Cdd:cd08834     6 IAEVKRLPGNDVCCDCGSPDPTWLSTNLGILTCIECSGVHRELGVHVSRIQSLTLDNLGTSELLLARNLGNEGFNEIMEA 85
                          90       100       110
                  ....*....|....*....|....*....|
gi 2462612273 689 ALGGYSKPGPDACREEKERWIRAKYEQKLF 718
Cdd:cd08834    86 NLPPGYKPTPNSDMEERKDFIRAKYVEKKF 115
ArfGap_SMAP cd08839
Stromal membrane-associated proteins; a subfamily of the ArfGAP family; The SMAP subfamily of ...
617-713 3.33e-36

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: 132.01  E-value: 3.33e-36
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462612273 617 GNSFCIDCDAPNPDWASLNLGALMCIECSGIHRHLGAHLSRVRSLDLDDWPPELLAVMTAMGNALANSVWEGAL-GGYSK 695
Cdd:cd08839     9 DNKYCADCGAKGPRWASWNLGVFICIRCAGIHRNLGVHISKVKSVNLDSWTPEQVQSMQEMGNARANAYYEANLpDGFRR 88
                          90
                  ....*....|....*...
gi 2462612273 696 PGPDAcreEKERWIRAKY 713
Cdd:cd08839    89 PQTDS---ALENFIRDKY 103
ArfGap_ARAP cd08837
ArfGap with Rho-Gap domain, ANK repeat and PH domain-containing proteins; The ARAP subfamily ...
609-718 5.63e-32

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: 120.17  E-value: 5.63e-32
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462612273 609 VQAVRTVRGNSFCIDCDAPNPDWASLNLGALMCIECSGIHRHLGAHLSRVRSLDLDD--WPPELLAVMTAMGNALANSVW 686
Cdd:cd08837     4 AEKIWSNPANRFCADCGAPDPDWASINLCVVICKQCAGEHRSLGSNISKVRSLKMDTkvWTEELVELFLKLGNDRANRFW 83
                          90       100       110
                  ....*....|....*....|....*....|....*.
gi 2462612273 687 EGALggysKPG----PDACREEKERWIRAKYEQKLF 718
Cdd:cd08837    84 AANL----PPSealhPDADSEQRREFITAKYREGKY 115
ArfGap_GIT cd08833
The GIT subfamily of ADP-ribosylation factor GTPase-activating proteins; The GIT (G-protein ...
612-713 8.83e-31

The GIT subfamily of ADP-ribosylation factor GTPase-activating proteins; The GIT (G-protein coupled receptor kinase-interacting protein) subfamily includes GIT1 and GIT2, which have three ANK repeats, a Spa-homology domain (SHD), a coiled-coil domain and a C-terminal paxillin-binding site (PBS). The GIT1/2 proteins are GTPase-activating proteins that function as an inactivator of Arf signaling, and interact with the PIX/Cool family of Rac/Cdc42 guanine nucleotide exchange factors (GEFs). Unlike other ArfGAPs, GIT and PIX (Pak-interacting exchange factor) proteins are tightly associated to form an oligomeric complex that acts as a scaffold and signal integrator that can be recruited for multiple signaling pathways. The GIT/PIX complex functions as a signaling scaffold by binding to specific protein partners. As a result, the complex is transported to specific cellular locations. For instance, the GIT partners paxillin or integrin-alpha4 (to focal adhesions), piccolo and liprin-alpha (to synapses), and the beta-PIX partner Scribble (to epithelial cell-cell contacts and synapses). Moreover, the GIT/PIT complex functions to integrate signals from multiple GTP-binding protein and protein kinase pathways to regulate the actin cytoskeleton and thus cell polarity, adhesion and migration.


Pssm-ID: 350062 [Multi-domain]  Cd Length: 109  Bit Score: 116.63  E-value: 8.83e-31
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462612273 612 VRTVRGNSF-CIDCDAPNPDWASLNLGALMCIECSGIHRHLGAHLSRVRSLDLDDWPPELLAVMTAMGNALANSVWEGAL 690
Cdd:cd08833     1 IRGKSSNARvCADCSAPDPEWASINRGVLICDECCSIHRSLGRHISQVKSLRKDQWPPSLLEMVQTLGNNGANSIWEHSL 80
                          90       100
                  ....*....|....*....|....*....
gi 2462612273 691 GGYS------KPGPDACREEKERWIRAKY 713
Cdd:cd08833    81 LDPSqsgkrkPIPPDPVHPTKEEFIKAKY 109
COG5347 COG5347
GTPase-activating protein that regulates ARFs (ADP-ribosylation factors), involved in ...
601-785 6.66e-29

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: 117.96  E-value: 6.66e-29
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462612273 601 GNQNAALAVQAVRTVRGNSFCIDCDAPNPDWASLNLGALMCIECSGIHRHLGAHLSRVRSLDLDDWPPELLAVMTAMGNA 680
Cdd:COG5347     3 TKSEDRKLLKLLKSDSSNKKCADCGAPNPTWASVNLGVFLCIDCAGVHRSLGVHISKVKSLTLDNWTEEELRRMEVGGNS 82
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462612273 681 LANSVWEG----ALGGYSKPGPDAcrEEKERWIRAKYEQKLFL----APLPSSDVPLGQQLLRAVVEDDLRLL-----VM 747
Cdd:COG5347    83 NANRFYEKnlldQLLLPIKAKYDS--SVAKKYIRKKYELKKFIddssSPSDFSSFSASSTRTVDSVDDRLDSEsqsrsSS 160
                         170       180       190       200
                  ....*....|....*....|....*....|....*....|....
gi 2462612273 748 LLAHGSKEEVNETYGDGDGRTALHL------SSAMANVVFTQLL 785
Cdd:COG5347   161 ASLGNSNRPDDELNVESFQSTGSKPrsltstKSNKDNLLNSELL 204
ArfGap_ArfGap1 cd08830
Arf1 GTPase-activating protein 1; ArfGAP (ADP Ribosylation Factor GTPase Activating Protein) ...
610-687 7.04e-29

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: 111.44  E-value: 7.04e-29
                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 2462612273 610 QAVRTVRGNSFCIDCDAPNPDWASLNLGALMCIECSGIHRHLGAHLSRVRSLDLDDWPPELLAVMTAMGNALANSVWE 687
Cdd:cd08830     6 RELQKLPGNNRCFDCGAPNPQWASVSYGIFICLECSGVHRGLGVHISFVRSITMDSWSEKQLKKMELGGNAKLREFFE 83
ArfGap_ArfGap1_like cd08959
ARF1 GTPase-activating protein 1-like; ArfGAP (ADP Ribosylation Factor GTPase Activating ...
610-683 3.77e-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: 3.77e-28
                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 2462612273 610 QAVRTVRGNSFCIDCDAPNPDWASLNLGALMCIECSGIHRHLGAHLSRVRSLDLDDWPPELLAVMTAMGNALAN 683
Cdd:cd08959     6 KKLRSKPENKVCFDCGAKNPQWASVTYGIFICLDCSGVHRGLGVHISFVRSTTMDKWTEEQLRKMKVGGNANAR 79
ArfGap_SMAP2 cd08859
Stromal membrane-associated protein 2; a subfamily of the ArfGAP family; The SMAP subfamily of ...
618-716 1.29e-27

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: 107.77  E-value: 1.29e-27
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462612273 618 NSFCIDCDAPNPDWASLNLGALMCIECSGIHRHLGAHLSRVRSLDLDDWPPELLAVMTAMGNALANSVWEGAL-GGYSKP 696
Cdd:cd08859    10 NKFCADCQSKGPRWASWNIGVFICIRCAGIHRNLGVHISRVKSVNLDQWTQEQIQCMQEMGNGKANRLYEAFLpENFRRP 89
                          90       100
                  ....*....|....*....|
gi 2462612273 697 GPDacrEEKERWIRAKYEQK 716
Cdd:cd08859    90 QTD---QAVEGFIRDKYEKK 106
ArfGap_ArfGap2_3_like cd08831
Arf1 GTPase-activating protein 2/3-like; ArfGAP (ADP Ribosylation Factor GTPase Activating ...
609-687 3.75e-27

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: 106.48  E-value: 3.75e-27
                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 2462612273 609 VQAVRTVRGNSFCIDCDAPNPDWASLNLGALMCIECSGIHRHLGAHLSRVRSLDLDDWPPELLAVMTAMGNALANSVWE 687
Cdd:cd08831     6 FKKLRSKPENKVCFDCGAKNPTWASVTFGVFLCLDCSGVHRSLGVHISFVRSTNLDSWTPEQLRRMKVGGNAKAREFFK 84
ArfGap_ADAP1 cd08843
ADAP1 GTPase activating protein for Arf, with dual PH domains; The ADAP subfamily, ArfGAPs ...
617-713 6.62e-27

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: 105.86  E-value: 6.62e-27
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462612273 617 GNSFCIDCDAPNPDWASLNLGALMCIECSGIHRHLgAHLSRVRSLDLDDWPPELLAVMTAMGNALANSVWEGALGG-YSK 695
Cdd:cd08843    16 GNARCADCGAPDPDWASYTLGVFICLSCSGIHRNI-PQVSKVKSVRLDAWEEAQVEFMASHGNDAARARFESKVPSfYYR 94
                          90
                  ....*....|....*...
gi 2462612273 696 PGPDACREEKERWIRAKY 713
Cdd:cd08843    95 PTPSDCQLLREQWIRAKY 112
ArfGap_ARAP1 cd17901
ArfGap with Rho-Gap domain, ANK repeat and PH domain-containing protein 1; The ARAP subfamily ...
610-715 2.25e-26

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: 104.51  E-value: 2.25e-26
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462612273 610 QAVRTVRGNSFCIDCDAPNPDWASLNLGALMCIECSGIHRHLGAHLSRVRSLDLDD--WPPELLAVMTAMGNALANSVWE 687
Cdd:cd17901     5 EKIWSVESNRFCADCGSPKPDWASVNLCVVICKRCAGEHRGLGPSVSKVRSLKMDRkvWTEELIELFLLLGNGKANQFWA 84
                          90       100
                  ....*....|....*....|....*...
gi 2462612273 688 GALGGYSKPGPDACREEKERWIRAKYEQ 715
Cdd:cd17901    85 ANVPPSEALCPSSSSEERRHFITAKYKE 112
ArfGap_ASAP1 cd08848
ArfGAP domain of ASAP1 (ArfGAP with SH3 domain, ANK repeat and PH domain-containing protein 1); ...
609-718 3.26e-26

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: 104.35  E-value: 3.26e-26
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462612273 609 VQAVRTVRGNSFCIDCDAPNPDWASLNLGALMCIECSGIHRHLGAHLSRVRSLDLDDWPPELLAVMTAMGNALANSVWEG 688
Cdd:cd08848     6 IDDVQRLPGNEVCCDCGSPDPTWLSTNLGILTCIECSGIHREMGVHISRIQSLELDKLGTSELLLAKNVGNNSFNDIMEG 85
                          90       100       110
                  ....*....|....*....|....*....|.
gi 2462612273 689 ALGGYS-KPGPDACREEKERWIRAKYEQKLF 718
Cdd:cd08848    86 NLPSPSpKPSPSSDMTARKEYITAKYVEHRF 116
ArfGap_ASAP3 cd17900
ArfGAP domain of ASAP3 (ArfGAP with ANK repeat and PH domain-containing protein 3); The ...
607-718 1.61e-25

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: 102.23  E-value: 1.61e-25
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462612273 607 LAVQAVRTVRGNSFCIDCDAPNPDWASLNLGALMCIECSGIHRHLGAHLSRVRSLDLDDWPPELLAVMTAMGNALANSVW 686
Cdd:cd17900     4 LLIAEVKSRPGNSQCCDCGAPDPTWLSTNLGILTCIECSGIHRELGVRYSRIQSLTLDLLSTSELLLAVSMGNTRFNEVM 83
                          90       100       110
                  ....*....|....*....|....*....|....
gi 2462612273 687 EGAL--GGYSKPGPDACREEKERWIRAKYEQKLF 718
Cdd:cd17900    84 EATLpaHGGPKPSAESDMGTRKDYIMAKYVEHRF 117
ArfGap_ADAP2 cd08844
ADAP2 GTPase activating protein for Arf, with dual PH domains; The ADAP subfamily, ArfGAPs ...
617-713 1.78e-25

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: 101.77  E-value: 1.78e-25
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462612273 617 GNSFCIDCDAPNPDWASLNLGALMCIECSGIHRHLGAhLSRVRSLDLDDWPPELLAVMTAMGNALANSVWEGALGG-YSK 695
Cdd:cd08844    16 GNSVCADCGAPDPDWASYTLGIFICLNCSGVHRNLPD-ISRVKSIRLDFWEDELVEFMKENGNLKAKAKFEAFVPPfYYR 94
                          90
                  ....*....|....*...
gi 2462612273 696 PGPDACREEKERWIRAKY 713
Cdd:cd08844    95 PQANDCDVLKEQWIRAKY 112
ArfGap_GIT2 cd08847
GIT2 GTPase activating protein for Arf; The GIT (G-protein coupled receptor kinase-interacting ...
613-713 3.47e-25

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: 100.87  E-value: 3.47e-25
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462612273 613 RTVRGNSFCIDCDAPNPDWASLNLGALMCIECSGIHRHLGAHLSRVRSLDLDDWPPELLAVMTAMGNALANSVWEGAL-- 690
Cdd:cd08847     3 KRLRSSEVCADCSTSDPRWASVNRGVLICDECCSVHRSLGRHISQVRHLKHTSWPPTLLQMVQTLYNNGANSIWEHSLld 82
                          90       100
                  ....*....|....*....|....*....
gi 2462612273 691 -----GGYSKPGP-DACREEKERWIRAKY 713
Cdd:cd08847    83 pasimSGKRKANPqDKVHPNKAEFIRAKY 111
ArfGap_ASAP2 cd08849
ArfGAP domain of ASAP2 (ArfGAP2 with SH3 domain, ANK repeat and PH domain-containing protein 2) ...
612-718 1.76e-23

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: 96.58  E-value: 1.76e-23
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462612273 612 VRTVRGNSFCIDCDAPNPDWASLNLGALMCIECSGIHRHLGAHLSRVRSLDLDDWPPELLAVMTAMGNALANSVWEGALG 691
Cdd:cd08849     9 VQRMTGNDVCCDCGAPDPTWLSTNLGILTCIECSGIHRELGVHYSRMQSLTLDVLGTSELLLAKNIGNAGFNEIMEACLP 88
                          90       100
                  ....*....|....*....|....*....
gi 2462612273 692 GYS--KPGPDACREEKERWIRAKYEQKLF 718
Cdd:cd08849    89 AEDvvKPNPGSDMNARKDYITAKYIERRY 117
ArfGap_ARAP3 cd17902
ArfGap with Rho-Gap domain, ANK repeat and PH domain-containing protein 3; The ARAP subfamily ...
616-718 4.21e-23

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: 94.98  E-value: 4.21e-23
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462612273 616 RGNSFCIDCDAPNPDWASLNLGALMCIECSGIHRHLGAHLSRVRSLDLDD--WPPELLAVMTAMGNALANSVWEGALGGY 693
Cdd:cd17902    11 KANRFCADCHASSPDWASINLCVVICKQCAGQHRSLGSGISKVQSLKLDTsvWSNEIVQLFIVLGNDRANRFWAARLPAS 90
                          90       100
                  ....*....|....*....|....*
gi 2462612273 694 SKPGPDACREEKERWIRAKYEQKLF 718
Cdd:cd17902    91 EALHPDATPEQRREFISRKYREGRF 115
Ras cd00876
Rat sarcoma (Ras) family of small guanosine triphosphatases (GTPases); The Ras family of the ...
130-286 5.02e-23

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: 96.44  E-value: 5.02e-23
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462612273 130 KVGIVGNLSSGKSALVHRYLTGTYVQEESP-EGGRFKKEIVVDGQSYLLLIRDEGGPPEL-----QFAAWVDAVVFVFSL 203
Cdd:cd00876     1 KLVVLGAGGVGKSALTIRFVSGEFVEEYDPtIEDSYRKQIVVDGETYTLDILDTAGQEEFsamrdQYIRNGDGFILVYSI 80
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462612273 204 EDEISFQTVYNYFLRLCSFRNASEVPMVLVGTQdaISAANPRVIDDSRARKLSTDLKrCTYYETCATYGLNVERVFQDVA 283
Cdd:cd00876    81 TSRESFEEIKNIREQILRVKDKEDVPIVLVGNK--CDLENERQVSTEEGEALAEEWG-CPFLETSAKTNINIDELFNTLV 157

                  ...
gi 2462612273 284 QKV 286
Cdd:cd00876   158 REI 160
ArfGap_ARAP2 cd08856
ArfGap with Rho-Gap domain, ANK repeat and PH domain-containing protein 2; The ARAP subfamily ...
618-718 1.80e-21

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: 90.74  E-value: 1.80e-21
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462612273 618 NSFCIDCDAPNPDWASLNLGALMCIECSGIHRHLGAHLSRVRSLDLDD--WPPELLAVMTAMGNALANSVWEGALGGYSK 695
Cdd:cd08856    18 NRSCADCKAPDPDWASINLCVVICKKCAGQHRSLGPKDSKVRSLKMDAsiWSNELIELFIVVGNKPANLFWAANLFSEED 97
                          90       100
                  ....*....|....*....|...
gi 2462612273 696 PGPDACREEKERWIRAKYEQKLF 718
Cdd:cd08856    98 LHMDSDVEQRTPFITQKYKEGKF 120
ArfGap_GIT1 cd08846
GIT1 GTPase activating protein for Arf; The GIT (G-protein coupled receptor kinase-interacting ...
613-713 1.46e-19

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: 84.77  E-value: 1.46e-19
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462612273 613 RTVRGNSFCIDCDAPNPDWASLNLGALMCIECSGIHRHLGAHLSRVRSLDLDDWPPELLAVMTAMGNALANSVWEGAL-- 690
Cdd:cd08846     3 RKGPRAEVCADCSAPDPGWASINRGVLICDECCSVHRSLGRHISIVKHLRHSAWPPTLLQMVHTLASNGANSIWEHSLld 82
                          90       100
                  ....*....|....*....|....*....
gi 2462612273 691 -----GGYSKPGP-DACREEKERWIRAKY 713
Cdd:cd08846    83 paqvqSGRRKANPqDKVHPTKSEFIRAKY 111
ArfGap_ArfGap3 cd09028
Arf1 GTPase-activating protein 3; ArfGAP (ADP Ribosylation Factor GTPase Activating Protein) ...
603-684 1.67e-19

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: 85.12  E-value: 1.67e-19
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462612273 603 QNAALAVQAVRTVRGNSFCIDCDAPNPDWASLNLGALMCIECSGIHRHLGAHLSRVRSLDLD-DWPPELLAVMTAMGNAL 681
Cdd:cd09028     4 QDIAAIFKRLRSVPTNKVCFDCGAKNPSWASITYGVFLCIDCSGIHRSLGVHLSFIRSTELDsNWSWFQLRCMQVGGNAN 83

                  ...
gi 2462612273 682 ANS 684
Cdd:cd09028    84 ASA 86
ArfGap_ArfGap2 cd09029
Arf1 GTPase-activating protein 2; ArfGAP (ADP Ribosylation Factor GTPase Activating Protein) ...
612-684 1.54e-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: 1.54e-18
                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 2462612273 612 VRTVRGNSFCIDCDAPNPDWASLNLGALMCIECSGIHRHLGAHLSRVRSLDLD-DWPPELLAVMTAMGNALANS 684
Cdd:cd09029    13 LRAIPTNKACFDCGAKNPSWASITYGVFLCIDCSGVHRSLGVHLSFIRSTELDsNWNWFQLRCMQVGGNANATA 86
PLN03114 PLN03114
ADP-ribosylation factor GTPase-activating protein AGD10; Provisional
602-730 1.53e-17

ADP-ribosylation factor GTPase-activating protein AGD10; Provisional


Pssm-ID: 178661 [Multi-domain]  Cd Length: 395  Bit Score: 85.68  E-value: 1.53e-17
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462612273 602 NQNAALAV-QAVRTVRGNSFCIDCDAPNPDWASLNLGALMCIECSGIHRHLGAHLSRVRSLDLDDWPPELLAVMTAMGNA 680
Cdd:PLN03114    5 NLNDKISVfKKLKAKSDNKICFDCNAKNPTWASVTYGIFLCIDCSAVHRSLGVHISFVRSTNLDSWSSEQLKMMIYGGNN 84
                          90       100       110       120       130       140
                  ....*....|....*....|....*....|....*....|....*....|....*....|.
gi 2462612273 681 LANSVWEG---ALGG-----YSKPGPDACREEKERWI-RAKYEQKLFLAPLP--SSDVPLG 730
Cdd:PLN03114   85 RAQVFFKQygwSDGGkteakYTSRAADLYKQILAKEVaKSKAEEELDLPPSPpdSTQVPNG 145
ArfGap_AGFG cd08838
ArfGAP domain of the AGFG subfamily (ArfGAP domain and FG repeat-containing proteins); The ...
617-718 4.62e-17

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: 77.62  E-value: 4.62e-17
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462612273 617 GNSFCIDCDAPNPDWASLNLGALMCIECSGIHRHLGaHlsRVRSLDLDDWPPELLAVMTAMGNALANSVWegaLGGY--- 693
Cdd:cd08838    12 ENKRCFDCGQRGPTYVNLTFGTFVCTTCSGIHREFN-H--RVKSISMSTFTPEEVEFLQAGGNEVARKIW---LAKWdpr 85
                          90       100
                  ....*....|....*....|....*.
gi 2462612273 694 SKPGPDACREEKER-WIRAKYEQKLF 718
Cdd:cd08838    86 TDPEPDSGDDQKIReFIRLKYVDKRW 111
small_GTPase smart00010
Small GTPase of the Ras superfamily; ill-defined subfamily; SMART predicts Ras-like small ...
127-292 5.18e-17

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: 79.14  E-value: 5.18e-17
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462612273  127 PELKVGIVGNLSSGKSALVHRYLTGTYVQEESP--EGGrFKKEIVVDGQSYLLLIRDEGGppELQFAAWVD-------AV 197
Cdd:smart00010   1 REYKLVVLGGGGVGKSALTIQFVQGHFVDEYDPtiEDS-YRKQIEIDGEVCLLDILDTAG--QEEFSAMRDqymrtgeGF 77
                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462612273  198 VFVFSLEDEISFQTVYNYFLRLCSFRNASEVPMVLVGTQ-DAIsaaNPRVIDDSRARKLSTDLKrCTYYETCATYGLNVE 276
Cdd:smart00010  78 LLVYSITDRQSFEEIAKFREQILRVKDRDDVPIVLVGNKcDLE---NERVVSTEEGKELARQWG-CPFLETSAKERINVD 153
                          170
                   ....*....|....*.
gi 2462612273  277 RVFQDVaqkVVALRKK 292
Cdd:smart00010 154 EAFYDL---VREIRKS 166
Rap_like cd04136
Rap-like family consists of Rap1, Rap2 and RSR1; The Rap subfamily consists of the Rap1, Rap2, ...
128-286 7.86e-17

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: 78.76  E-value: 7.86e-17
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462612273 128 ELKVGIVGNLSSGKSALVHRYLTGTYVQEESPE-GGRFKKEIVVDGQSYLLLIRDEGGPPelQFAAWVD-------AVVF 199
Cdd:cd04136     1 EYKLVVLGSGGVGKSALTVQFVQGIFVDKYDPTiEDSYRKQIEVDCQQCMLEILDTAGTE--QFTAMRDlyikngqGFAL 78
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462612273 200 VFSLEDEISFQTVYNYFLRLCSFRNASEVPMVLVGTQdaISAANPRVIDDSRARKLSTDLKRCTYYETCATYGLNVERVF 279
Cdd:cd04136    79 VYSITAQQSFNDLQDLREQILRVKDTEDVPMILVGNK--CDLEDERVVSKEEGQNLARQWGNCPFLETSAKSKINVDEIF 156

                  ....*..
gi 2462612273 280 QDVAQKV 286
Cdd:cd04136   157 YDLVRQI 163
RAS smart00173
Ras subfamily of RAS small GTPases; Similar in fold and function to the bacterial EF-Tu GTPase. ...
130-292 1.07e-16

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: 78.37  E-value: 1.07e-16
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462612273  130 KVGIVGNLSSGKSALVHRYLTGTYVQEESP--EGGrFKKEIVVDGQSYLLLIRDEGGppELQFAAWVD-------AVVFV 200
Cdd:smart00173   2 KLVVLGSGGVGKSALTIQFIQGHFVDDYDPtiEDS-YRKQIEIDGEVCLLDILDTAG--QEEFSAMRDqymrtgeGFLLV 78
                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462612273  201 FSLEDEISFQTVYNYFLRLCSFRNASEVPMVLVGTQ-DAIsaaNPRVIDDSRARKLSTDLKrCTYYETCATYGLNVERVF 279
Cdd:smart00173  79 YSITDRQSFEEIKKFREQILRVKDRDDVPIVLVGNKcDLE---SERVVSTEEGKELARQWG-CPFLETSAKERVNVDEAF 154
                          170
                   ....*....|...
gi 2462612273  280 QDVaqkVVALRKK 292
Cdd:smart00173 155 YDL---VREIRKK 164
Rab7 cd01862
Rab GTPase family 7 (Rab7); Rab7 subfamily. Rab7 is a small Rab GTPase that regulates ...
129-291 1.08e-16

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: 78.48  E-value: 1.08e-16
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462612273 129 LKVGIVGNLSSGKSALVHRYLTGTYVQE-ESPEGGRF-KKEIVVDGQSYLLLIRDEGGPPELQ-----FAAWVDAVVFVF 201
Cdd:cd01862     1 LKVIILGDSGVGKTSLMNQYVNKKFSNQyKATIGADFlTKEVTVDDRLVTLQIWDTAGQERFQslgvaFYRGADCCVLVY 80
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462612273 202 SLEDEISFQTVYNY---FLRLCSFRNASEVPMVLVGTQdaISAANPRVIDDSRARKLSTDLKRCTYYETCATYGLNVERV 278
Cdd:cd01862    81 DVTNPKSFESLDSWrdeFLIQASPRDPENFPFVVLGNK--IDLEEKRQVSTKKAQQWCKSKGNIPYFETSAKEAINVDQA 158
                         170
                  ....*....|...
gi 2462612273 279 FQDVAQKVVALRK 291
Cdd:cd01862   159 FETIARLALEQEK 171
RSR1 cd04177
RSR1/Bud1p family GTPase; RSR1/Bud1p is a member of the Rap subfamily of the Ras family that ...
128-287 3.17e-16

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: 77.14  E-value: 3.17e-16
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462612273 128 ELKVGIVGNLSSGKSALVHRYLTGTYVQEESPE-GGRFKKEIVVDGQSYLLLIRDEGGPPelQFAAWVD-------AVVF 199
Cdd:cd04177     1 DYKIVVLGAGGVGKSALTVQFVQNVFIESYDPTiEDSYRKQVEIDGRQCDLEILDTAGTE--QFTAMRElyiksgqGFLL 78
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462612273 200 VFSLEDEISFQTVYNYFLRLCSFRNASEVPMVLVGTQ-DAIsaaNPRVIDDSRARKLSTDLKRCTYYETCATYGLNVERV 278
Cdd:cd04177    79 VYSVTSEASLNELGELREQVLRIKDSDNVPMVLVGNKaDLE---DDRQVSREDGVSLSQQWGNVPFYETSARKRTNVDEV 155

                  ....*....
gi 2462612273 279 FQDVAQKVV 287
Cdd:cd04177   156 FIDLVRQII 164
Rab cd00154
Ras-related in brain (Rab) family of small guanosine triphosphatases (GTPases); Rab GTPases ...
129-284 4.92e-16

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: 76.34  E-value: 4.92e-16
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462612273 129 LKVGIVGNLSSGKSALVHRYLTGTYVQEESPE-GGRFK-KEIVVDGQSYLLLIRDEGGppelQ--FAAWV-------DAV 197
Cdd:cd00154     1 FKIVLIGDSGVGKTSLLLRFVDNKFSENYKSTiGVDFKsKTIEVDGKKVKLQIWDTAG----QerFRSITssyyrgaHGA 76
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462612273 198 VFVFSLEDEISFQTVYNYFLRLCSFRNaSEVPMVLVGTQdaISAANPRVIDDSRARKLSTDLKrCTYYETCATYGLNVER 277
Cdd:cd00154    77 ILVYDVTNRESFENLDKWLNELKEYAP-PNIPIILVGNK--SDLEDERQVSTEEAQQFAKENG-LLFFETSAKTGENVDE 152

                  ....*..
gi 2462612273 278 VFQDVAQ 284
Cdd:cd00154   153 AFESLAR 159
Ras pfam00071
Ras family; Includes sub-families Ras, Rab, Rac, Ral, Ran, Rap Ypt1 and more. Shares P-loop ...
130-286 9.70e-16

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: 75.63  E-value: 9.70e-16
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462612273 130 KVGIVGNLSSGKSALVHRYLTGTYVQE-ESPEGGRFK-KEIVVDGQSYLLLIRDEGGPPElqFAA-----WVDAVVF--V 200
Cdd:pfam00071   1 KLVLVGDGGVGKSSLLIRFTQNKFPEEyIPTIGVDFYtKTIEVDGKTVKLQIWDTAGQER--FRAlrplyYRGADGFllV 78
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462612273 201 FSLEDEISFQTVYNYF---LRLCSfrnaSEVPMVLVGTQdaISAANPRVIDDSRARKLSTDLKrCTYYETCATYGLNVER 277
Cdd:pfam00071  79 YDITSRDSFENVKKWVeeiLRHAD----ENVPIVLVGNK--CDLEDQRVVSTEEGEALAKELG-LPFMETSAKTNENVEE 151

                  ....*....
gi 2462612273 278 VFQDVAQKV 286
Cdd:pfam00071 152 AFEELAREI 160
Rap1 cd04175
Rap1 family GTPase consists of Rap1a and Rap1b isoforms; The Rap1 subgroup is part of the Rap ...
128-286 1.71e-14

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: 72.16  E-value: 1.71e-14
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462612273 128 ELKVGIVGNLSSGKSALVHRYLTGTYVQEESPE-GGRFKKEIVVDGQSYLLLIRDEGGPPelQFAAWVD-------AVVF 199
Cdd:cd04175     1 EYKLVVLGSGGVGKSALTVQFVQGIFVEKYDPTiEDSYRKQVEVDGQQCMLEILDTAGTE--QFTAMRDlymkngqGFVL 78
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462612273 200 VFSLEDEISF---QTVYNYFLRLcsfRNASEVPMVLVGTQdaISAANPRVIDDSRARKLSTDLKrCTYYETCATYGLNVE 276
Cdd:cd04175    79 VYSITAQSTFndlQDLREQILRV---KDTEDVPMILVGNK--CDLEDERVVGKEQGQNLARQWG-CAFLETSAKAKINVN 152
                         170
                  ....*....|
gi 2462612273 277 RVFQDVAQKV 286
Cdd:cd04175   153 EIFYDLVRQI 162
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, ...
127-286 1.16e-13

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: 69.74  E-value: 1.16e-13
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462612273 127 PELKVGIVGNLSSGKSALVHRYLTGTYVQEESPE-GGRFKKEIVVDGQSYLLLIRDEGGPPEL-----QFAAWVDAVVFV 200
Cdd:cd04145     1 PTYKLVVVGGGGVGKSALTIQFIQSYFVTDYDPTiEDSYTKQCEIDGQWARLDILDTAGQEEFsamreQYMRTGEGFLLV 80
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462612273 201 FSLEDEISFQTVYNYFLRLCSFRNASEVPMVLVGTQdaISAANPRVIDDSRARKLSTDLKrCTYYETCATYGLNVERVFQ 280
Cdd:cd04145    81 FSVTDRGSFEEVDKFHTQILRVKDRDEFPMILVGNK--ADLEHQRQVSREEGQELARQLK-IPYIETSAKDRVNVDKAFH 157

                  ....*.
gi 2462612273 281 DVAQKV 286
Cdd:cd04145   158 DLVRVI 163
Ras_like_GTPase cd00882
Rat sarcoma (Ras)-like superfamily of small guanosine triphosphatases (GTPases); Ras-like ...
132-284 1.71e-13

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: 69.02  E-value: 1.71e-13
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462612273 132 GIVGNLSSGKSALVHRYLTGTYVQEESPEG---GRFKKEIVVDGQSYLLLIRDEGGPPE----------LQFAAWVDAVV 198
Cdd:cd00882     1 VVVGRGGVGKSSLLNALLGGEVGEVSDVPGttrDPDVYVKELDKGKVKLVLVDTPGLDEfgglgreelaRLLLRGADLIL 80
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462612273 199 FVFSLEDEISFQTVYNYFLRLcsfRNASEVPMVLVGTQ-DAISAANPRVIDDSRARKLSTDLKrctYYETCATYGLNVER 277
Cdd:cd00882    81 LVVDSTDRESEEDAKLLILRR---LRKEGIPIILVGNKiDLLEEREVEELLRLEELAKILGVP---VFEVSAKTGEGVDE 154

                  ....*..
gi 2462612273 278 VFQDVAQ 284
Cdd:cd00882   155 LFEKLIE 161
RERG_RasL11_like cd04146
Ras-related and Estrogen-Regulated Growth inhibitor (RERG) and Ras-like 11 (RasL11)-like ...
130-286 2.05e-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: 68.84  E-value: 2.05e-13
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462612273 130 KVGIVGNLSSGKSALVHRYLTGTYVQE-ESPEGGRFKKEIVVDGQSYLLLIRDEGGPPELQ-------FAAWVDAVVFVF 201
Cdd:cd04146     1 KIAVLGASGVGKSALTVRFLTKRFIGEyEPNLESLYSRQVTIDGEQVSLEIQDTPGQQQNEdpeslerSLRWADGFVLVY 80
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462612273 202 SLEDEISFQTV--YNYFLRLCSfRNASEVPMVLVGT-QDaisAANPRVIDDSRARKLSTDLkRCTYYE--TCATYgLNVE 276
Cdd:cd04146    81 SITDRSSFDVVsqLLQLIREIK-KRDGEIPVILVGNkAD---LLHSRQVSTEEGQKLALEL-GCLFFEvsAAENY-LEVQ 154
                         170
                  ....*....|
gi 2462612273 277 RVFQDVAQKV 286
Cdd:cd04146   155 NVFHELCREV 164
RheB cd04137
Ras Homolog Enriched in Brain (RheB) is a small GTPase; Rheb (Ras Homolog Enriched in Brain) ...
130-279 3.77e-13

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: 68.43  E-value: 3.77e-13
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462612273 130 KVGIVGNLSSGKSALVHRYLTGTYVQEESP--EgGRFKKEIVVDGQSYLLLIRDEGGPPEL-----QFAAWVDAVVFVFS 202
Cdd:cd04137     3 KIAVLGSRSVGKSSLTVQFVEGHFVESYYPtiE-NTFSKIITYKGQEYHLEIVDTAGQDEYsilpqKYSIGIHGYILVYS 81
                          90       100       110       120       130       140       150
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 2462612273 203 LEDEISFQTVYNYFLRLCSFRNASEVPMVLVGTQDAISaaNPRVIDDSRARKLSTDLKrCTYYETCATYGLNVERVF 279
Cdd:cd04137    82 VTSRKSFEVVKVIYDKILDMLGKESVPIVLVGNKSDLH--MERQVSAEEGKKLAESWG-AAFLESSAKENENVEEAF 155
RAB smart00175
Rab subfamily of small GTPases; Rab GTPases are implicated in vesicle trafficking.
129-289 4.48e-13

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


Pssm-ID: 197555 [Multi-domain]  Cd Length: 164  Bit Score: 67.92  E-value: 4.48e-13
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462612273  129 LKVGIVGNLSSGKSALVHRYLTGTYVQEESPEGG-RFK-KEIVVDGQSYLLLIRDEGGppelQ------FAAW---VDAV 197
Cdd:smart00175   1 FKIILIGDSGVGKSSLLSRFTDGKFSEQYKSTIGvDFKtKTIEVDGKRVKLQIWDTAG----QerfrsiTSSYyrgAVGA 76
                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462612273  198 VFVFSLEDEISFQTVYNYFLRLCSFRNaSEVPMVLVGTQdaISAANPRVIDDSRARKLSTDLKrCTYYETCATYGLNVER 277
Cdd:smart00175  77 LLVYDITNRESFENLENWLKELREYAS-PNVVIMLVGNK--SDLEEQRQVSREEAEAFAEEHG-LPFFETSAKTNTNVEE 152
                          170
                   ....*....|..
gi 2462612273  278 VFQDVAQKVVAL 289
Cdd:smart00175 153 AFEELAREILKR 164
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, ...
128-286 6.51e-13

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: 67.44  E-value: 6.51e-13
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462612273 128 ELKVGIVGNLSSGKSALVHRYLTGTYVQEESPE-GGRFKKEIVVDGQSYLLLIRDEGGPPEL-----QFAAWVDAVVFVF 201
Cdd:cd04138     1 EYKLVVVGAGGVGKSALTIQLIQNHFVDEYDPTiEDSYRKQVVIDGETCLLDILDTAGQEEYsamrdQYMRTGEGFLCVF 80
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462612273 202 SLEDEISFQTVYNYFLRLCSFRNASEVPMVLVGTQDAISAanpRVIDDSRARKLSTDLKrCTYYETCATYGLNVERVFQD 281
Cdd:cd04138    81 AINSRKSFEDIHTYREQIKRVKDSDDVPMVLVGNKCDLAA---RTVSTRQGQDLAKSYG-IPYIETSAKTRQGVEEAFYT 156

                  ....*
gi 2462612273 282 VAQKV 286
Cdd:cd04138   157 LVREI 161
Rap2 cd04176
Rap2 family GTPase consists of Rap2a, Rap2b, and Rap2c; The Rap2 subgroup is part of the Rap ...
128-286 3.79e-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: 65.24  E-value: 3.79e-12
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462612273 128 ELKVGIVGNLSSGKSALVHRYLTGTYVQEESPEGGRF-KKEIVVDGQSYLLLIRDEGGPPelQFAAWVD-------AVVF 199
Cdd:cd04176     1 EYKVVVLGSGGVGKSALTVQFVSGTFIEKYDPTIEDFyRKEIEVDSSPSVLEILDTAGTE--QFASMRDlyikngqGFIV 78
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462612273 200 VFSLEDEISFQTVYNYFLRLCSFRNASEVPMVLVGTQdaISAANPRVIDDSRARKLSTDLKrCTYYETCATYGLNVERVF 279
Cdd:cd04176    79 VYSLVNQQTFQDIKPMRDQIVRVKGYEKVPIILVGNK--VDLESEREVSSAEGRALAEEWG-CPFMETSAKSKTMVNELF 155

                  ....*..
gi 2462612273 280 QDVAQKV 286
Cdd:cd04176   156 AEIVRQM 162
Gem1 COG1100
GTPase SAR1 family domain [General function prediction only];
128-284 8.89e-12

GTPase SAR1 family domain [General function prediction only];


Pssm-ID: 440717 [Multi-domain]  Cd Length: 177  Bit Score: 64.62  E-value: 8.89e-12
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462612273 128 ELKVGIVGNLSSGKSALVHRYLTGTYVQEE--SPEG-GRFKKEIVVDGQSYLLLIRDEGGPPEL-----QFAAWV---DA 196
Cdd:COG1100     3 EKKIVVVGTGGVGKTSLVNRLVGDIFSLEKylSTNGvTIDKKELKLDGLDVDLVIWDTPGQDEFretrqFYARQLtgaSL 82
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462612273 197 VVFVFSLEDEISFQTVYNYFLRLcsFRNASEVPMVLVGTQ-DAISaaNPRVIDDSRARKLSTDLKRCTYYETCATYGLNV 275
Cdd:COG1100    83 YLFVVDGTREETLQSLYELLESL--RRLGKKSPIILVLNKiDLYD--EEEIEDEERLKEALSEDNIVEVVATSAKTGEGV 158

                  ....*....
gi 2462612273 276 ERVFQDVAQ 284
Cdd:COG1100   159 EELFAALAE 167
Rab9 cd04116
Rab GTPase family 9 (Rab9); Rab9 is found in late endosomes, together with mannose 6-phosphate ...
129-286 1.13e-11

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: 64.12  E-value: 1.13e-11
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462612273 129 LKVGIVGNLSSGKSALVHRYLTGTY-VQEESPEGGRF-KKEIVVDGQSYLLLIRDEGGPPELQ-----FAAWVDAVVFVF 201
Cdd:cd04116     6 LKVILLGDGGVGKSSLMNRYVTNKFdTQLFHTIGVEFlNKDLEVDGHFVTLQIWDTAGQERFRslrtpFYRGSDCCLLTF 85
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462612273 202 SLEDEISFQTVYNY---FLRLCSFRNASEVPMVLVGTQDAISAanpRVIDDSRARKLSTDLKRCTYYETCATYGLNVERV 278
Cdd:cd04116    86 SVDDSQSFQNLSNWkkeFIYYADVKEPESFPFVILGNKIDIPE---RQVSTEEAQAWCRDNGDYPYFETSAKDATNVAAA 162

                  ....*...
gi 2462612273 279 FQDVAQKV 286
Cdd:cd04116   163 FEEAVRRV 170
ANKYR COG0666
Ankyrin repeat [Signal transduction mechanisms];
733-822 2.33e-11

Ankyrin repeat [Signal transduction mechanisms];


Pssm-ID: 440430 [Multi-domain]  Cd Length: 289  Bit Score: 65.36  E-value: 2.33e-11
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462612273 733 LLRAVVEDDLRLLVMLLAHGskEEVNETygDGDGRTALHLSSAMANVVFTQLLIWYGVDVRSRDARGLTPLAYARRAGSQ 812
Cdd:COG0666    91 LHAAARNGDLEIVKLLLEAG--ADVNAR--DKDGETPLHLAAYNGNLEIVKLLLEAGADVNAQDNDGNTPLHLAAANGNL 166
                          90
                  ....*....|
gi 2462612273 813 ECADILIQHG 822
Cdd:COG0666   167 EIVKLLLEAG 176
ANKYR COG0666
Ankyrin repeat [Signal transduction mechanisms];
733-822 6.34e-11

Ankyrin repeat [Signal transduction mechanisms];


Pssm-ID: 440430 [Multi-domain]  Cd Length: 289  Bit Score: 64.20  E-value: 6.34e-11
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462612273 733 LLRAVVEDDLRLLVMLLAHGSkeEVNETygDGDGRTALHLSSAMANVVFTQLLIWYGVDVRSRDARGLTPLAYARRAGSQ 812
Cdd:COG0666   124 LHLAAYNGNLEIVKLLLEAGA--DVNAQ--DNDGNTPLHLAAANGNLEIVKLLLEAGADVNARDNDGETPLHLAAENGHL 199
                          90
                  ....*....|
gi 2462612273 813 ECADILIQHG 822
Cdd:COG0666   200 EIVKLLLEAG 209
Rab23_like cd04106
Rab GTPase family 23 (Rab23)-like; Rab23-like subfamily. Rab23 is a member of the Rab family ...
129-285 8.35e-11

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: 61.30  E-value: 8.35e-11
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462612273 129 LKVGIVGNLSSGKSALVHRYLTGTYVQEespeggrFKKEIVVD-----------GQSYLLLIRDEGGPPElqFAAWVD-- 195
Cdd:cd04106     1 IKVIVVGNGNVGKSSMIQRFVKGIFTKD-------YKKTIGVDflekqiflrqsDEDVRLMLWDTAGQEE--FDAITKay 71
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462612273 196 -----AVVFVFSLEDEISFQTVYNYflRLCSFRNASEVPMVLVgtQDAISAANPRVIDDSRARKLSTDLKrCTYYETCAT 270
Cdd:cd04106    72 yrgaqACILVFSTTDRESFEAIESW--KEKVEAECGDIPMVLV--QTKIDLLDQAVITNEEAEALAKRLQ-LPLFRTSVK 146
                         170
                  ....*....|....*
gi 2462612273 271 YGLNVERVFQDVAQK 285
Cdd:cd04106   147 DDFNVTELFEYLAEK 161
ArfGap_AGFG1 cd08857
ArfGAP domain of AGFG1 (ArfGAP domain and FG repeat-containing protein 1); The ArfGAP domain ...
618-716 7.68e-10

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: 57.36  E-value: 7.68e-10
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462612273 618 NSFCIDCDAPNPDWASLNLGALMCIECSGIHRHLGAHlSRVRSLDLDDWPPELLAVMTAMGNALANSVWEGALGGYSKPG 697
Cdd:cd08857    14 NRKCFDCDQRGPTYANMTVGSFVCTSCSGILRGLNPP-HRVKSISMTTFTQQEIEFLQKHGNEVCKQIWLGLFDDRSSAI 92
                          90       100
                  ....*....|....*....|
gi 2462612273 698 PDACREEK-ERWIRAKYEQK 716
Cdd:cd08857    93 PDFRDPQKvKEFLQEKYEKK 112
RalA_RalB cd04139
Ral (Ras-like) family containing highly homologous RalA and RalB; The Ral (Ras-like) subfamily ...
130-286 1.98e-09

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: 57.44  E-value: 1.98e-09
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462612273 130 KVGIVGNLSSGKSALVHRYLTGTYVQEESP-EGGRFKKEIVVDGQSYLLLIRDEGGPPE-----LQFAAWVDAVVFVFSL 203
Cdd:cd04139     2 KVIMVGSGGVGKSALTLQFMYDEFVEDYEPtKADSYRKKVVLDGEEVQLNILDTAGQEDyaairDNYFRSGEGFLLVFSI 81
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462612273 204 EDEISFQTVYNYFLRLCSFRNASEVPMVLVGTQDAISAANPRVIDDSRARKLSTDLKrctYYETCATYGLNVERVFQDVA 283
Cdd:cd04139    82 TDMESFTALAEFREQILRVKEDDNVPLLLVGNKCDLEDKRQVSVEEAANLAEQWGVN---YVETSAKTRANVDKVFFDLV 158

                  ...
gi 2462612273 284 QKV 286
Cdd:cd04139   159 REI 161
ANKYR COG0666
Ankyrin repeat [Signal transduction mechanisms];
733-822 2.27e-09

Ankyrin repeat [Signal transduction mechanisms];


Pssm-ID: 440430 [Multi-domain]  Cd Length: 289  Bit Score: 59.58  E-value: 2.27e-09
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462612273 733 LLRAVVEDDLRLLVMLLAHGSkeEVNETygDGDGRTALHLSSAMANVVFTQLLIWYGVDVRSRDARGLTPLAYARRAGSQ 812
Cdd:COG0666   157 LHLAAANGNLEIVKLLLEAGA--DVNAR--DNDGETPLHLAAENGHLEIVKLLLEAGADVNAKDNDGKTALDLAAENGNL 232
                          90
                  ....*....|
gi 2462612273 813 ECADILIQHG 822
Cdd:COG0666   233 EIVKLLLEAG 242
Ank_2 pfam12796
Ankyrin repeats (3 copies);
733-823 3.58e-09

Ankyrin repeats (3 copies);


Pssm-ID: 463710 [Multi-domain]  Cd Length: 91  Bit Score: 54.35  E-value: 3.58e-09
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462612273 733 LLRAVVEDDLRLLVMLLAHGSKEEVNetygDGDGRTALHLSSAMANVVFTQLLIWYgVDVRSRDaRGLTPLAYARRAGSQ 812
Cdd:pfam12796   1 LHLAAKNGNLELVKLLLENGADANLQ----DKNGRTALHLAAKNGHLEIVKLLLEH-ADVNLKD-NGRTALHYAARSGHL 74
                          90
                  ....*....|.
gi 2462612273 813 ECADILIQHGC 823
Cdd:pfam12796  75 EIVKLLLEKGA 85
ANKYR COG0666
Ankyrin repeat [Signal transduction mechanisms];
711-822 1.38e-08

Ankyrin repeat [Signal transduction mechanisms];


Pssm-ID: 440430 [Multi-domain]  Cd Length: 289  Bit Score: 57.27  E-value: 1.38e-08
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462612273 711 AKYEQKLFLAPLPSSDVPLGQQLLRAVVEDDLRLLVMLLAHGSkeeVNETYGDGDGRTALHLSSAMANVVFTQLLIWYGV 790
Cdd:COG0666    35 LLLLLLLLALLALALADALGALLLLAAALAGDLLVALLLLAAG---ADINAKDDGGNTLLHAAARNGDLEIVKLLLEAGA 111
                          90       100       110
                  ....*....|....*....|....*....|..
gi 2462612273 791 DVRSRDARGLTPLAYARRAGSQECADILIQHG 822
Cdd:COG0666   112 DVNARDKDGETPLHLAAYNGNLEIVKLLLEAG 143
RGK cd04148
Rem, Rem2, Rad, Gem/Kir (RGK) subfamily of Ras GTPases; RGK subfamily. The RGK (Rem, Rem2, Rad, ...
129-292 1.55e-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: 55.87  E-value: 1.55e-08
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462612273 129 LKVGIVGNLSSGKSALVHRYLTGTY----VQEESPEGGrfKKEIVVDGQSYLLLIRDeggPPELQFAAWV--------DA 196
Cdd:cd04148     1 YRVVLLGDSGVGKSSLANIFTAGVYedsaYEASGDDTY--ERTVSVDGEEATLVVYD---HWEQEDGMWLedscmqvgDA 75
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462612273 197 VVFVFSLEDEISFQTVYNYFLRLCSFRNASEVPMVLVGTQDAIsaANPRVIDDSRARKLSTDLKrCTYYETCATYGLNVE 276
Cdd:cd04148    76 YVIVYSVTDRSSFEKASELRIQLRRARQAEDIPIILVGNKSDL--VRSREVSVQEGRACAVVFD-CKFIETSAALQHNVD 152
                         170
                  ....*....|....*..
gi 2462612273 277 RVFQD-VAQkvVALRKK 292
Cdd:cd04148   153 ELFEGiVRQ--VRLRRD 167
PTZ00369 PTZ00369
Ras-like protein; Provisional
128-286 5.14e-08

Ras-like protein; Provisional


Pssm-ID: 240385 [Multi-domain]  Cd Length: 189  Bit Score: 53.71  E-value: 5.14e-08
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462612273 128 ELKVGIVGNLSSGKSALVHRYLTGTYVQEESPE-GGRFKKEIVVDGQSYLLLIRDEGGPPEL-----QFAAWVDAVVFVF 201
Cdd:PTZ00369    5 EYKLVVVGGGGVGKSALTIQFIQNHFIDEYDPTiEDSYRKQCVIDEETCLLDILDTAGQEEYsamrdQYMRTGQGFLCVY 84
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462612273 202 SLEDEISFQTVYNYFLRLCSFRNASEVPMVLVGTQDAISaaNPRVIDDSRARKLSTDLKrCTYYETCATYGLNVERVFQD 281
Cdd:PTZ00369   85 SITSRSSFEEIASFREQILRVKDKDRVPMILVGNKCDLD--SERQVSTGEGQELAKSFG-IPFLETSAKQRVNVDEAFYE 161

                  ....*
gi 2462612273 282 VAQKV 286
Cdd:PTZ00369  162 LVREI 166
RJL cd04119
Rab GTPase family J-like (RabJ-like); RJLs are found in many protists and as chimeras with ...
129-288 1.29e-07

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: 52.36  E-value: 1.29e-07
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462612273 129 LKVGIVGNLSSGKSALVHRYLTGTYVQEESPEGG---------RFKKEIVVD-----GQSYLLLIRDEggppelqFAAWV 194
Cdd:cd04119     1 IKVISMGNSGVGKSCIIKRYCEGRFVSKYLPTIGidygvkkvsVRNKEVRVNffdlsGHPEYLEVRNE-------FYKDT 73
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462612273 195 DAVVFVFSLEDEISFQTVYNYFLRLCSF----RNASEVPMVLVGTQdaISAANPRVIDDSRARKLSTDLKrCTYYETCAT 270
Cdd:cd04119    74 QGVLLVYDVTDRQSFEALDSWLKEMKQEggphGNMENIVVVVCANK--IDLTKHRAVSEDEGRLWAESKG-FKYFETSAC 150
                         170
                  ....*....|....*...
gi 2462612273 271 YGLNVERVFQDVAQKVVA 288
Cdd:cd04119   151 TGEGVNEMFQTLFSSIVD 168
Wrch_1 cd04130
Wnt-1 responsive Cdc42 homolog (Wrch-1) is a Rho family GTPase similar to Cdc42; Wrch-1 (Wnt-1 ...
129-279 2.43e-07

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: 51.63  E-value: 2.43e-07
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462612273 129 LKVGIVGNLSSGKSALVHRYLTGTYVQEESPEG-GRFKKEIVVDGQSYLLLIRDEGGPPE---LQFAAWVDAVVFV--FS 202
Cdd:cd04130     1 LKCVLVGDGAVGKTSLIVSYTTNGYPTEYVPTAfDNFSVVVLVDGKPVRLQLCDTAGQDEfdkLRPLCYPDTDVFLlcFS 80
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462612273 203 LEDEISFQTVYNYFLRLCSFRNASeVPMVLVGTQ------------DAISAANPrvIDDSRARKLSTDLKRCTYYETCAT 270
Cdd:cd04130    81 VVNPSSFQNISEKWIPEIRKHNPK-APIILVGTQadlrtdvnvliqLARYGEKP--VSQSRAKALAEKIGACEYIECSAL 157

                  ....*....
gi 2462612273 271 YGLNVERVF 279
Cdd:cd04130   158 TQKNLKEVF 166
Rho cd00157
Ras homology family (Rho) of small guanosine triphosphatases (GTPases); Members of the Rho ...
129-284 4.73e-07

Ras homology family (Rho) of small guanosine triphosphatases (GTPases); Members of the Rho (Ras homology) family include RhoA, Cdc42, Rac, Rnd, Wrch1, RhoBTB, and Rop. There are 22 human Rho family members identified currently. These proteins are all involved in the reorganization of the actin cytoskeleton in response to external stimuli. They also have roles in cell transformation by Ras in cytokinesis, in focal adhesion formation and in the stimulation of stress-activated kinase. These various functions are controlled through distinct effector proteins and mediated through a GTP-binding/GTPase cycle involving three classes of regulating proteins: GAPs (GTPase-activating proteins), GEFs (guanine nucleotide exchange factors), and GDIs (guanine nucleotide dissociation inhibitors). 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. Since crystal structures often lack C-terminal residues, this feature is not available for annotation in many of the CDs in the hierarchy.


Pssm-ID: 206641 [Multi-domain]  Cd Length: 171  Bit Score: 50.62  E-value: 4.73e-07
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462612273 129 LKVGIVGNLSSGKSALVHRYLTGTYVQEESP---EGgrFKKEIVVDGQSYLLLIRDEGGPPE------LQFAAwVDAVVF 199
Cdd:cd00157     1 IKIVVVGDGAVGKTCLLISYTTNKFPTEYVPtvfDN--YSANVTVDGKQVNLGLWDTAGQEEydrlrpLSYPQ-TDVFLL 77
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462612273 200 VFSLEDEISFQTVYNYF---LRlcsfRNASEVPMVLVGTQ-DAISAANPRV--------IDDSRARKLSTDLKRCTYYET 267
Cdd:cd00157    78 CFSVDSPSSFENVKTKWypeIK----HYCPNVPIILVGTKiDLRDDGNTLKklekkqkpITPEEGEKLAKEIGAVKYMEC 153
                         170
                  ....*....|....*..
gi 2462612273 268 CATYGLNVERVFQDVAQ 284
Cdd:cd00157   154 SALTQEGLKEVFDEAIR 170
Rit_Rin_Ric cd04141
Ras-like protein in all tissues (Rit), Ras-like protein in neurons (Rin) and Ras-related ...
128-296 7.42e-07

Ras-like protein in all tissues (Rit), Ras-like protein in neurons (Rin) and Ras-related protein which interacts with calmodulin (Ric); Rit (Ras-like protein in all tissues), Rin (Ras-like protein in neurons) and Ric (Ras-related protein which interacts with calmodulin) form a subfamily with several unique structural and functional characteristics. These proteins all lack a the C-terminal CaaX lipid-binding motif typical of Ras family proteins, and Rin and Ric contain calmodulin-binding domains. Rin, which is expressed only in neurons, induces neurite outgrowth in rat pheochromocytoma cells through its association with calmodulin and its activation of endogenous Rac/cdc42. Rit, which is ubiquitously expressed in mammals, inhibits growth-factor withdrawl-mediated apoptosis and induces neurite extension in pheochromocytoma cells. Rit and Rin are both able to form a ternary complex with PAR6, a cell polarity-regulating protein, and Rac/cdc42. This ternary complex is proposed to have physiological function in processes such as tumorigenesis. Activated Ric is likely to signal in parallel with the Ras pathway or stimulate the Ras pathway at some upstream point, and binding of calmodulin to Ric may negatively regulate Ric activity.


Pssm-ID: 206712 [Multi-domain]  Cd Length: 172  Bit Score: 50.24  E-value: 7.42e-07
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462612273 128 ELKVGIVGNLSSGKSALVHRYLTGTYVQEESPE-GGRFKKEIVVDGQSYLLLIRDEGGPPEL-----QFAAWVDAVVFVF 201
Cdd:cd04141     2 EYKIVMLGAGGVGKSAVTMQFISHSFPDYHDPTiEDAYKTQARIDNEPALLDILDTAGQAEFtamrdQYMRCGEGFIICY 81
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462612273 202 SLEDEISFQTVYNYFLRLCSFRNASEVPMVLVGTQdaISAANPRVIDDSRARKLSTDLKrCTYYETCATYGLNVERVFQD 281
Cdd:cd04141    82 SVTDRHSFQEASEFKELITRVRLTEDIPLVLVGNK--VDLEQQRQVTTEEGRNLAREFN-CPFFETSAALRFYIDDAFHG 158
                         170
                  ....*....|....*
gi 2462612273 282 VAQKVvalRKKQQLA 296
Cdd:cd04141   159 LVREI---RRKESMP 170
Rhes_like cd04143
Ras homolog enriched in striatum (Rhes) and activator of G-protein signaling 1 (Dexras1/AGS1); ...
130-372 9.62e-07

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: 50.90  E-value: 9.62e-07
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462612273 130 KVGIVGNLSSGKSALVHRYLTGTYVQEESPEGGRF-KKEIVVDGQSYLLLIRDEGGppELQFAAWV-------DAVVFVF 201
Cdd:cd04143     2 RMVVLGASKVGKTAIVSRFLGGRFEEQYTPTIEDFhRKLYSIRGEVYQLDILDTSG--NHPFPAMRrlsiltgDVFILVF 79
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462612273 202 SLEDEISFQTVynyflrlCSFRN---------------ASEVPMVLVGTQDAISAanPRVIDDSRARKLSTDLKRCTYYE 266
Cdd:cd04143    80 SLDNRESFEEV-------CRLREqiletksclknktkeNVKIPMVICGNKADRDF--PREVQRDEVEQLVGGDENCAYFE 150
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462612273 267 TCATYGLNVERVFQDVAqkvvALRKkqqlaigpcksLPN--SPS-HSAVSAASIPAVHINQATNGGGSAFSD-YSSSVPS 342
Cdd:cd04143   151 VSAKKNSNLDEMFRALF----SLAK-----------LPNemSPSlHRKISVQYGDALHKKSRGGSRKRKEGDaCGAVAPF 215
                         250       260       270
                  ....*....|....*....|....*....|..
gi 2462612273 343 T--PSISQrELRIetIAASSTPtpiRKQSKRR 372
Cdd:cd04143   216 ArrPSVHS-DLRY--IRSKSTG---GGQSKDK 241
PH smart00233
Pleckstrin homology domain; Domain commonly found in eukaryotic signalling proteins. The ...
405-584 2.07e-06

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: 47.16  E-value: 2.07e-06
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462612273  405 PIKQGILLKRSGKSlNKEWKKKYVTLCdNGLLTYHPSLHDYMQNIHGKEIDLLRTTVKVPgkrlpratpatapgtspran 484
Cdd:smart00233   1 VIKEGWLYKKSGGG-KKSWKKRYFVLF-NSTLLYYKSKKDKKSYKPKGSIDLSGCTVREA-------------------- 58
                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462612273  485 glsversntqlgggtasgpaevlsssPKLDPPPSPHSnrkkhrrkkstgtprpdgpssateeaeesfeFVVVSLTGQTWH 564
Cdd:smart00233  59 --------------------------PDPDSSKKPHC-------------------------------FEIKTSDRKTLL 81
                          170       180
                   ....*....|....*....|
gi 2462612273  565 FEASTAEERELWVQSVQAQI 584
Cdd:smart00233  82 LQAESEEEREKWVEALRKAI 101
ArfGap_AGFG2 cd17903
ArfGAP domain of AGFG2 (ArfGAP domain and FG repeat-containing protein 2); The ArfGAP domain ...
617-716 2.10e-06

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: 47.29  E-value: 2.10e-06
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462612273 617 GNSFCIDCDAPNPDWASLNLGALMCIECSGIHRHLGAHlSRVRSLDLDDWPPELLAVMTAMGNALANSVWEGALGGYSKP 696
Cdd:cd17903    13 ANRHCFECAQRGVTYVDITVGSFVCTTCSGLLRGLNPP-HRVKSISMTTFTEPEVLFLQARGNEVCRKIWLGLFDARTSL 91
                          90       100
                  ....*....|....*....|.
gi 2462612273 697 GPDACREEK-ERWIRAKYEQK 716
Cdd:cd17903    92 IPDSRDPQKvKEFLQEKYEKK 112
Spg1 cd04128
Septum-promoting GTPase (Spg1); Spg1p. Spg1p (septum-promoting GTPase) was first identified in ...
129-289 2.29e-06

Septum-promoting GTPase (Spg1); Spg1p. Spg1p (septum-promoting GTPase) was first identified in the fission yeast S. pombe, where it regulates septum formation in the septation initiation network (SIN) through the cdc7 protein kinase. Spg1p is an essential gene that localizes to the spindle pole bodies. When GTP-bound, it binds cdc7 and causes it to translocate to spindle poles. Sid4p (septation initiation defective) is required for localization of Spg1p to the spindle pole body, and the ability of Spg1p to promote septum formation from any point in the cell cycle depends on Sid4p. Spg1p is negatively regulated by Byr4 and cdc16, which form a two-component GTPase activating protein (GAP) for Spg1p. The existence of a SIN-related pathway in plants has been proposed. 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: 206701 [Multi-domain]  Cd Length: 182  Bit Score: 48.93  E-value: 2.29e-06
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462612273 129 LKVGIVGNLSSGKSALVHRYLTGTYVQEESPEGGR--FKKEIVVDGQSYLLLIRDEGGppELQFA-----AWVDAVV--F 199
Cdd:cd04128     1 LKIGLLGDAQIGKTSLMVKYVEGEFDEEYIQTLGVnfMEKTISIRGTEITFSIWDLGG--QREFInmlplVCKDAVAilF 78
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462612273 200 VFSLEDEISFQTVYNYFLRLCSFrNASEVPmVLVGTQDAISAANPRVIDD---SRARKLSTDLKrCTYYETCATYGLNVE 276
Cdd:cd04128    79 MFDLTRKSTLNSIKEWYRQARGF-NKTAIP-ILVGTKYDLFADLPPEEQEeitKQARKYAKAMK-APLIFCSTSHSINVQ 155
                         170
                  ....*....|...
gi 2462612273 277 RVFQDVAQKVVAL 289
Cdd:cd04128   156 KIFKFVLAKVFDL 168
Ran cd00877
Ras-related nuclear proteins (Ran)/TC4 family of small GTPases; Ran GTPase is involved in ...
130-287 5.40e-06

Ras-related nuclear proteins (Ran)/TC4 family of small GTPases; Ran GTPase is involved in diverse biological functions, such as nuclear transport, spindle formation during mitosis, DNA replication, and cell division. Among the Ras superfamily, Ran is a unique small G protein. It does not have a lipid modification motif at the C-terminus to bind to the membrane, which is often observed within the Ras superfamily. Ran may therefore interact with a wide range of proteins in various intracellular locations. Like other GTPases, Ran exists in GTP- and GDP-bound conformations that interact differently with effectors. Conversion between these forms and the assembly or disassembly of effector complexes requires the interaction of regulator proteins. The intrinsic GTPase activity of Ran is very low, but it is greatly stimulated by a GTPase-activating protein (RanGAP1) located in the cytoplasm. By contrast, RCC1, a guanine nucleotide exchange factor that generates RanGTP, is bound to chromatin and confined to the nucleus. Ran itself is mobile and is actively imported into the nucleus by a mechanism involving NTF-2. Together with the compartmentalization of its regulators, this is thought to produce a relatively high concentration of RanGTP in the nucleus.


Pssm-ID: 206643 [Multi-domain]  Cd Length: 166  Bit Score: 47.30  E-value: 5.40e-06
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462612273 130 KVGIVGNLSSGKSALVHRYLTGtyvqeespeggRFKKEIV--VDGQSYLLLIRDEGGPpeLQFAAW-------------- 193
Cdd:cd00877     2 KLVLVGDGGTGKTTFVKRHLTG-----------EFEKKYVatLGVEVHPLDFHTNRGK--IRFNVWdtagqekfgglrdg 68
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462612273 194 ----VDAVVFVFSLEDEISFQTVYNYFLRLCsfRNASEVPMVLVGTQDAISaanprvIDDSRARKLSTDLKRCT-YYETC 268
Cdd:cd00877    69 yyiqGQCAIIMFDVTSRVTYKNVPNWHRDLV--RVCENIPIVLCGNKVDIK------DRKVKPKQITFHRKKNLqYYEIS 140
                         170
                  ....*....|....*....
gi 2462612273 269 ATYGLNVERVFQDVAQKVV 287
Cdd:cd00877   141 AKSNYNFEKPFLWLARKLL 159
Ras_dva cd04147
Ras - dorsal-ventral anterior localization (Ras-dva) family; Ras-dva subfamily. Ras-dva (Ras - ...
140-296 6.89e-06

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: 47.53  E-value: 6.89e-06
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462612273 140 GKSALVHRYLTGTYvqeeSPEGGR-----FKKEIVVDGQSYLLLIRDEGGPPElqFAAW-------VDAVVFVFSLEDEI 207
Cdd:cd04147    11 GKTALIQRFLYDTF----EPKHRRtveelHSKEYEVAGVKVTIDILDTSGSYS--FPAMrklsiqnGDAFALVYSVDDPE 84
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462612273 208 SFQTVYNYFLRLCSFRNASEVPMVLVGTQdaISAANPRVIDDSRARKLSTDLKRCTYYETCATYGLNVERVFQDVAQKV- 286
Cdd:cd04147    85 SFEEVKRLREEILEVKEDKFVPIVVVGNK--IDSLAERQVEAADALSTVELDWNNGFVEASAKDNENVTEVFKELLQQAn 162
                         170
                  ....*....|....*.
gi 2462612273 287 ------VALRKKQQLA 296
Cdd:cd04147   163 lpswlsPALRRRRESA 178
Rab27A cd04127
Rab GTPase family 27a (Rab27a); The Rab27a subfamily consists of Rab27a and its highly ...
129-277 9.31e-06

Rab GTPase family 27a (Rab27a); The Rab27a subfamily consists of Rab27a and its highly homologous isoform, Rab27b. Unlike most Rab proteins whose functions remain poorly defined, Rab27a has many known functions. Rab27a has multiple effector proteins, and depending on which effector it binds, Rab27a has different functions as well as tissue distribution and/or cellular localization. Putative functions have been assigned to Rab27a when associated with the effector proteins Slp1, Slp2, Slp3, Slp4, Slp5, DmSlp, rabphilin, Dm/Ce-rabphilin, Slac2-a, Slac2-b, Slac2-c, Noc2, JFC1, and Munc13-4. Rab27a has been associated with several human diseases, including hemophagocytic syndrome (Griscelli syndrome or GS), Hermansky-Pudlak syndrome, and choroidermia. In the case of GS, a rare, autosomal recessive disease, a Rab27a mutation is directly responsible for the disorder. When Rab27a is localized to the secretory granules of pancreatic beta cells, it is believed to mediate glucose-stimulated insulin secretion, making it a potential target for diabetes therapy. When bound to JFC1 in prostate cells, Rab27a is believed to regulate the exocytosis of prostate- specific markers. 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: 206700 [Multi-domain]  Cd Length: 180  Bit Score: 47.11  E-value: 9.31e-06
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462612273 129 LKVGIVGNLSSGKSALVHRYLTGTY-VQEESPEGGRFKKEIVV-----------DGQSYLLLIRDEGGPPE---LQFAAW 193
Cdd:cd04127     5 IKLLALGDSGVGKTTFLYRYTDNKFnPKFITTVGIDFREKRVVynsqgpdgtsgKAFRVHLQLWDTAGQERfrsLTTAFF 84
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462612273 194 VDAVVF--VFSLEDEISFQTVYNYFLRLCSFRNASEVPMVLVGTQDAISaaNPRVIDDSRARKLSTDLkRCTYYETCATY 271
Cdd:cd04127    85 RDAMGFllMFDLTSEQSFLNVRNWMSQLQAHAYCENPDIVLIGNKADLP--DQREVSERQARELADKY-GIPYFETSAAT 161

                  ....*.
gi 2462612273 272 GLNVER 277
Cdd:cd04127   162 GQNVEK 167
ARHI_like cd04140
A Ras homolog member I (ARHI); ARHI (A Ras homolog member I) is a member of the Ras family ...
130-280 2.27e-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: 45.59  E-value: 2.27e-05
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462612273 130 KVGIVGNLSSGKSALVHRYLTGTYVQEESPE-GGRFKKEIVVDGQSYLLLIRDEGGP---PELQFAAWVD--AVVFVFSL 203
Cdd:cd04140     3 RVVVFGAGGVGKSSLVLRFVKGTFRESYIPTiEDTYRQVISCSKSICTLQITDTTGShqfPAMQRLSISKghAFILVYSI 82
                          90       100       110       120       130       140       150
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 2462612273 204 EDEISFQTVYNYFLRLCSFR--NASEVPMVLVGTQDAISAAnpRVIDDSRARKLSTDLKrCTYYETCATYGLNVERVFQ 280
Cdd:cd04140    83 TSKQSLEELKPIYELICEIKgnNLEKIPIMLVGNKCDESPS--REVSSSEGAALARTWN-CAFMETSAKTNHNVQELFQ 158
PTZ00322 PTZ00322
6-phosphofructo-2-kinase/fructose-2,6-biphosphatase; Provisional
763-844 2.48e-05

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


Pssm-ID: 140343 [Multi-domain]  Cd Length: 664  Bit Score: 47.97  E-value: 2.48e-05
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462612273 763 DGDGRTALHLSSAMANVVFTQLLIWYGVDVRSRDARGLTPLAYARRAGSQECADILIQH----------GCPGEGCGLAP 832
Cdd:PTZ00322  112 DYDGRTPLHIACANGHVQVVRVLLEFGADPTLLDKDGKTPLELAEENGFREVVQLLSRHsqchfelganAKPDSFTGKPP 191
                          90
                  ....*....|..
gi 2462612273 833 TPNREPANGTNP 844
Cdd:PTZ00322  192 SLEDSPISSHHP 203
PLN03131 PLN03131
hypothetical protein; Provisional
613-743 2.48e-05

hypothetical protein; Provisional


Pssm-ID: 178677 [Multi-domain]  Cd Length: 705  Bit Score: 47.85  E-value: 2.48e-05
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462612273 613 RTVRG------NSFCIDCDAPNPDWASLNLGALMCIECSGIHRHLgAHlsRVRSLDLDDWPPELLAVMTAMGNALANSVW 686
Cdd:PLN03131   12 KIIRGlmklppNRRCINCNSLGPQFVCTNFWTFICMTCSGIHREF-TH--RVKSVSMSKFTSQDVEALQNGGNQRAREIY 88
                          90       100       110       120       130
                  ....*....|....*....|....*....|....*....|....*....|....*...
gi 2462612273 687 EGALGGYSKPGPDACREEKER-WIRAKYEQKLFLAPLPSSDVPLGQQLLRAvVEDDLR 743
Cdd:PLN03131   89 LKDWDQQRQRLPDNSKVDKIReFIKDIYVDKKYAGGKTHDKPPRDLQRIRS-HEDETR 145
Roc pfam08477
Ras of Complex, Roc, domain of DAPkinase; Roc, or Ras of Complex, proteins are mitochondrial ...
130-235 5.57e-05

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: 43.26  E-value: 5.57e-05
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462612273 130 KVGIVGNLSSGKSALVHRYLTGTYVQEESPEGGrfkkeivVDGQSYLLLIRDEGGpPELQFAAW---------------- 193
Cdd:pfam08477   1 KVVLLGDSGVGKTSLLKRFVDDTFDPKYKSTIG-------VDFKTKTVLENDDNG-KKIKLNIWdtagqerfrslhpfyy 72
                          90       100       110       120
                  ....*....|....*....|....*....|....*....|....
gi 2462612273 194 --VDAVVFVFsleDEISFQTVYNYFLRLCsfRNASEVPMVLVGT 235
Cdd:pfam08477  73 rgAAAALLVY---DSRTFSNLKYWLRELK--KYAGNSPVILVGN 111
Rab24 cd04118
Rab GTPase family 24 (Rab24); Rab24 is distinct from other Rabs in several ways. It exists ...
129-300 1.11e-04

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: 44.09  E-value: 1.11e-04
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462612273 129 LKVGIVGNLSSGKSALVHRYLTGTYVQE--ESPEGGRF-KKEIVVDGQSYLLLIRDEGGPPELQ-----FAAWVDAVVFV 200
Cdd:cd04118     1 VKVVMLGKESVGKTSLVERYVHHRFLVGpyQNTIGAAFvAKRMVVGERVVTLGIWDTAGSERYEamsriYYRGAKAAIVC 80
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462612273 201 FSLEDEISFQTVYNYFLRLCSfrNASEVPMVLVGTQ-DAISA-ANPRVIDDSRARKLSTDLKrCTYYETCATYGLNVERV 278
Cdd:cd04118    81 YDLTDSSSFERAKFWVKELQN--LEEHCKIYLCGTKsDLIEQdRSLRQVDFHDVQDFADEIK-AQHFETSSKTGQNVDEL 157
                         170       180       190
                  ....*....|....*....|....*....|....*
gi 2462612273 279 FQDVAQ-------------KVVALRKKQQLAIGPC 300
Cdd:cd04118   158 FQKVAEdfvsrannqmnteKGVDLGQKKNSYFYSC 192
Ank_5 pfam13857
Ankyrin repeats (many copies);
748-806 1.56e-04

Ankyrin repeats (many copies);


Pssm-ID: 433530 [Multi-domain]  Cd Length: 56  Bit Score: 40.41  E-value: 1.56e-04
                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....*....
gi 2462612273 748 LLAHGSkEEVNetYGDGDGRTALHLSSAMANVVFTQLLIWYGVDVRSRDARGLTPLAYA 806
Cdd:pfam13857   1 LLEHGP-IDLN--RLDGEGYTPLHVAAKYGALEIVRVLLAYGVDLNLKDEEGLTALDLA 56
RabL2 cd04124
Rab GTPase-like family 2 (Rab-like2); RabL2 (Rab-like2) subfamily. RabL2s are novel Rab ...
129-287 1.72e-04

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: 42.92  E-value: 1.72e-04
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462612273 129 LKVGIVGNLSSGKSALVHRYLTGTY--VQEESPEGGRFKKEIVVDGQSYLLLIRDEGGPPELQ--FAAW---VDAVVFVF 201
Cdd:cd04124     1 VKIILLGDSAVGKSKLVERFLMDGYepQQLSTYALTLYKHNAKFEGKTILVDFWDTAGQERFQtmHASYyhkAHACILVF 80
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462612273 202 SLEDEISFQTVYNYFLRLCSFRnaSEVPMVLVGTQdaiSAANPRVIDDSRARKLSTDLkrcTYYETCATYGLNVERVFQD 281
Cdd:cd04124    81 DVTRKITYKNLSKWYEELREYR--PEIPCIVVANK---IDLDPSVTQKKFNFAEKHNL---PLYYVSAADGTNVVKLFQD 152

                  ....*.
gi 2462612273 282 VAQKVV 287
Cdd:cd04124   153 AIKLAV 158
Rab35 cd04110
Rab GTPase family 35 (Rab35); Rab35 is one of several Rab proteins to be found to participate ...
130-296 4.31e-04

Rab GTPase family 35 (Rab35); Rab35 is one of several Rab proteins to be found to participate in the regulation of osteoclast cells in rats. In addition, Rab35 has been identified as a protein that interacts with nucleophosmin-anaplastic lymphoma kinase (NPM-ALK) in human cells. Overexpression of NPM-ALK is a key oncogenic event in some anaplastic large-cell lymphomas; since Rab35 interacts with N|PM-ALK, it may provide a target for cancer treatments. 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: 133310 [Multi-domain]  Cd Length: 199  Bit Score: 42.53  E-value: 4.31e-04
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462612273 130 KVGIVGNLSSGKSALVHRY----LTGTYVqeeSPEGGRFK-KEIVVDGQSYLLLIRDEGGPPELQ-----FAAWVDAVVF 199
Cdd:cd04110     8 KLLIIGDSGVGKSSLLLRFadntFSGSYI---TTIGVDFKiRTVEINGERVKLQIWDTAGQERFRtitstYYRGTHGVIV 84
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462612273 200 VFSLEDEISFQTVYNYFLRLCSfrNASEVPMVLVGTQDAISAAnpRVIDDSRARKLSTDLKrCTYYETCATYGLNVERVF 279
Cdd:cd04110    85 VYDVTNGESFVNVKRWLQEIEQ--NCDDVCKVLVGNKNDDPER--KVVETEDAYKFAGQMG-ISLFETSAKENINVEEMF 159
                         170
                  ....*....|....*..
gi 2462612273 280 QDVAQKVVaLRKKQQLA 296
Cdd:cd04110   160 NCITELVL-RAKKDNLA 175
Rab6 cd01861
Rab GTPase family 6 (Rab6); Rab6 is involved in microtubule-dependent transport pathways ...
130-285 5.51e-04

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: 41.45  E-value: 5.51e-04
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462612273 130 KVGIVGNLSSGKSALVHRYLTGTYVQEESPEGGR--FKKEIVVDGQSYLLLIRDEGG--------PPELQFAAwvdAVVF 199
Cdd:cd01861     2 KLVFLGDQSVGKTSIITRFMYDTFDNQYQATIGIdfLSKTMYVDDKTVRLQLWDTAGqerfrsliPSYIRDSS---VAVV 78
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462612273 200 VFSLEDEISFQTVYNYFLRLCSFRNaSEVPMVLVGTQdaISAANPRVIDDSRARKLSTDLKrCTYYETCATYGLNVERVF 279
Cdd:cd01861    79 VYDITNRQSFDNTDKWIDDVRDERG-NDVIIVLVGNK--TDLSDKRQVSTEEGEKKAKENN-AMFIETSAKAGHNVKQLF 154

                  ....*.
gi 2462612273 280 QDVAQK 285
Cdd:cd01861   155 KKIAQA 160
PHA03095 PHA03095
ankyrin-like protein; Provisional
728-823 5.77e-04

ankyrin-like protein; Provisional


Pssm-ID: 222980 [Multi-domain]  Cd Length: 471  Bit Score: 43.47  E-value: 5.77e-04
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462612273 728 PLGQQLLRAVVEDDLRLLVmllAHGskeeVNETYGDGDGRTALH--LSSAMANVVFTQLLIWYGVDVRSRDARGLTPLA- 804
Cdd:PHA03095   86 PLHLYLYNATTLDVIKLLI---KAG----ADVNAKDKVGRTPLHvyLSGFNINPKVIRLLLRKGADVNALDLYGMTPLAv 158
                          90       100
                  ....*....|....*....|
gi 2462612273 805 YARRAG-SQECADILIQHGC 823
Cdd:PHA03095  159 LLKSRNaNVELLRLLIDAGA 178
PH_ACAP cd13250
ArfGAP with coiled-coil, ankyrin repeat and PH domains Pleckstrin homology (PH) domain; ACAP ...
407-463 5.88e-04

ArfGAP with coiled-coil, ankyrin repeat and PH domains Pleckstrin homology (PH) domain; ACAP (also called centaurin beta) functions both as a Rab35 effector and as an Arf6-GTPase-activating protein (GAP) by which it controls actin remodeling and membrane trafficking. ACAP contain an NH2-terminal bin/amphiphysin/Rvs (BAR) domain, a phospholipid-binding domain, a PH domain, a GAP domain, and four ankyrin repeats. The AZAPs constitute a family of Arf GAPs that are characterized by an NH2-terminal pleckstrin homology (PH) domain and a central Arf GAP domain followed by two or more ankyrin repeats. On the basis of sequence and domain organization, the AZAP family is further subdivided into four subfamilies: 1) the ACAPs contain an NH2-terminal bin/amphiphysin/Rvs (BAR) domain (a phospholipid-binding domain that is thought to sense membrane curvature), a single PH domain followed by the GAP domain, and four ankyrin repeats; 2) the ASAPs also contain an NH2-terminal BAR domain, the tandem PH domain/GAP domain, three ankyrin repeats, two proline-rich regions, and a COOH-terminal Src homology 3 domain; 3) the AGAPs contain an NH2-terminal GTPase-like domain (GLD), a split PH domain, and the GAP domain followed by four ankyrin repeats; and 4) the ARAPs contain both an Arf GAP domain and a Rho GAP domain, as well as an NH2-terminal sterile-a motif (SAM), a proline-rich region, a GTPase-binding domain, and five PH domains. PMID 18003747 and 19055940 Centaurin can bind to 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: 270070  Cd Length: 98  Bit Score: 39.90  E-value: 5.88e-04
                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....*..
gi 2462612273 407 KQGILLKRSGKSlNKEWKKKYVTLcDNGLLTYHPSLHDYMQNIHgkEIDLLRTTVKV 463
Cdd:cd13250     1 KEGYLFKRSSNA-FKTWKRRWFSL-QNGQLYYQKRDKKDEPTVM--VEDLRLCTVKP 53
PLN03119 PLN03119
putative ADP-ribosylation factor GTPase-activating protein AGD14; Provisional
618-743 5.97e-04

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


Pssm-ID: 178666  Cd Length: 648  Bit Score: 43.30  E-value: 5.97e-04
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462612273 618 NSFCIDCDAPNPDWASLNLGALMCIECSGIHRHLgahLSRVRSLDLDDWPPELLAVMTAMGNALANSVWEGALGGYSKPG 697
Cdd:PLN03119   23 NRRCINCNSLGPQYVCTTFWTFVCMACSGIHREF---THRVKSVSMSKFTSKEVEVLQNGGNQRAREIYLKNWDHQRQRL 99
                          90       100       110       120
                  ....*....|....*....|....*....|....*....|....*..
gi 2462612273 698 PDACREEKER-WIRAKYEQKLFlAPLPSSDVPLGQQLLRAVVEDDLR 743
Cdd:PLN03119  100 PENSNAERVReFIKNVYVQKKY-AGANDADKPSKDSQDHVSSEDMTR 145
Rab5_related cd01860
Rab-related GTPase family includes Rab5 and Rab22; regulates early endosome fusion; The ...
128-286 9.91e-04

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: 40.61  E-value: 9.91e-04
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462612273 128 ELKVGIVGNLSSGKSALVHRYLTGTYVQEESPEGGR--FKKEIVVDGQSYLLLIRDEGG--------PPELQFAAwvdAV 197
Cdd:cd01860     1 QFKLVLLGDSSVGKSSIVLRFVKNEFSENQESTIGAafLTQTVNLDDTTVKFEIWDTAGqeryrslaPMYYRGAA---AA 77
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462612273 198 VFVFSLEDEISFQTVYNYF--LRlcsfRNAS-EVPMVLVGTQdaISAANPRVIDDSRARKLSTDLKrCTYYETCATYGLN 274
Cdd:cd01860    78 IVVYDITSEESFEKAKSWVkeLQ----EHGPpNIVIALAGNK--ADLESKRQVSTEEAQEYADENG-LLFMETSAKTGEN 150
                         170
                  ....*....|..
gi 2462612273 275 VERVFQDVAQKV 286
Cdd:cd01860   151 VNELFTEIARKL 162
TRPV5-6 cd22192
Transient Receptor Potential channel, Vanilloid subfamily (TRPV), types 5 and 6; TRPV5 and ...
723-822 1.13e-03

Transient Receptor Potential channel, Vanilloid subfamily (TRPV), types 5 and 6; TRPV5 and TRPV6 (TRPV5/6) are two homologous members within the vanilloid subfamily of the transient receptor potential (TRP) family. TRPV5 and TRPV6 show only 30-40% homology with other members of the TRP family and have unique properties that differentiates them from other TRP channels. They mediate calcium uptake in epithelia and their expression is dramatically increased in numerous types of cancer. The structure of TRPV5/6 shows the typical topology features of all TRP family members, such as six transmembrane regions, a short hydrophobic stretch between transmembrane segments 5 and 6, which is predicted to form the Ca2+ pore, and large intracellular N- and C-terminal domains. The N-terminal domain of TRPV5/6 contains three ankyrin repeats. This structural element is present in several proteins and plays a role in protein-protein interactions. The N- and C-terminal tails of TRPV5/6 each contain an internal PDZ motif which can function as part of a molecular scaffold via interaction with PDZ-domain containing proteins. A major difference between the properties of TRPV5 and TRPV6 is in their tissue distribution: TRPV5 is predominantly expressed in the distal convoluted tubules (DCT) and connecting tubules (CNT) of the kidney, with limited expression in extrarenal tissues. In contrast, TRPV6 has a broader expression pattern such as expression in the intestine, kidney, placenta, epididymis, exocrine tissues, and a few other tissues.


Pssm-ID: 411976 [Multi-domain]  Cd Length: 609  Bit Score: 42.69  E-value: 1.13e-03
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462612273 723 PSSDV----PLGQQLLRAVVEDDLRLLVMLLAHGSKEEVNE--TYGDGDGRTALHLSSAMANVVFTQLLIWYGVDVRSRD 796
Cdd:cd22192    40 PSCDLfqrgALGETALHVAALYDNLEAAVVLMEAAPELVNEpmTSDLYQGETALHIAVVNQNLNLVRELIARGADVVSPR 119
                          90       100       110       120
                  ....*....|....*....|....*....|....*....|
gi 2462612273 797 ARGLT--------------PLAYARRAGSQECADILIQHG 822
Cdd:cd22192   120 ATGTFfrpgpknliyygehPLSFAACVGNEEIVRLLIEHG 159
Rab3 cd01865
Rab GTPase family 3 contains Rab3A, Rab3B, Rab3C and Rab3D; The Rab3 subfamily contains Rab3A, ...
129-280 1.18e-03

Rab GTPase family 3 contains Rab3A, Rab3B, Rab3C and Rab3D; The Rab3 subfamily contains Rab3A, Rab3B, Rab3C, and Rab3D. All four isoforms were found in mouse brain and endocrine tissues, with varying levels of expression. Rab3A, Rab3B, and Rab3C localized to synaptic and secretory vesicles; Rab3D was expressed at high levels only in adipose tissue, exocrine glands, and the endocrine pituitary, where it is localized to cytoplasmic secretory granules. Rab3 appears to control Ca2+-regulated exocytosis. The appropriate GDP/GTP exchange cycle of Rab3A is required for Ca2+-regulated exocytosis to occur, and interaction of the GTP-bound form of Rab3A with effector molecule(s) is widely believed to be essential for this process. Functionally, most studies point toward a role for Rab3 in the secretion of hormones and neurotransmitters. 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: 206657 [Multi-domain]  Cd Length: 165  Bit Score: 40.67  E-value: 1.18e-03
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462612273 129 LKVGIVGNLSSGKSALVHRY----LTGTYVqeeSPEGGRFKKEIVVDGQSYL-LLIRDEGGP---PELQFAAWVDAVVFV 200
Cdd:cd01865     2 FKLLIIGNSSVGKTSFLFRYaddsFTSAFV---STVGIDFKVKTVYRNDKRIkLQIWDTAGQeryRTITTAYYRGAMGFI 78
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462612273 201 --FSLEDEISFQTVYNYFLRL--CSFRNASevpMVLVGTQdaISAANPRVIDDSRARKLSTDLKrCTYYETCATYGLNVE 276
Cdd:cd01865    79 lmYDITNEESFNAVQDWSTQIktYSWDNAQ---VILVGNK--CDMEDERVVSAERGRQLADQLG-FEFFEASAKENINVK 152

                  ....
gi 2462612273 277 RVFQ 280
Cdd:cd01865   153 QVFE 156
Ank_4 pfam13637
Ankyrin repeats (many copies);
733-786 1.71e-03

Ankyrin repeats (many copies);


Pssm-ID: 372654 [Multi-domain]  Cd Length: 54  Bit Score: 37.25  E-value: 1.71e-03
                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....
gi 2462612273 733 LLRAVVEDDLRLLVMLLAHGSkeEVNETygDGDGRTALHLSSAMANVVFTQLLI 786
Cdd:pfam13637   5 LHAAAASGHLELLRLLLEKGA--DINAV--DGNGETALHFAASNGNVEVLKLLL 54
PH pfam00169
PH domain; PH stands for pleckstrin homology.
405-584 2.07e-03

PH domain; PH stands for pleckstrin homology.


Pssm-ID: 459697 [Multi-domain]  Cd Length: 105  Bit Score: 38.70  E-value: 2.07e-03
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462612273 405 PIKQGILLKRSGKsLNKEWKKKYVTLCDNGLLTYHPSLHDYMQNIHGKeIDLLRTTVKvpgkrlpratpatapgtspran 484
Cdd:pfam00169   1 VVKEGWLLKKGGG-KKKSWKKRYFVLFDGSLLYYKDDKSGKSKEPKGS-ISLSGCEVV---------------------- 56
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462612273 485 glsversntqlgggtasgpaevlssspklDPPPSPHSNRKKHrrkkstgtprpdgpssateeaeesFEFVVVSLTG-QTW 563
Cdd:pfam00169  57 -----------------------------EVVASDSPKRKFC------------------------FELRTGERTGkRTY 83
                         170       180
                  ....*....|....*....|.
gi 2462612273 564 HFEASTAEERELWVQSVQAQI 584
Cdd:pfam00169  84 LLQAESEEERKDWIKAIQSAI 104
RabL4 cd04101
Rab GTPase-like family 4 (Rab-like4); RabL4 (Rab-like4) subfamily. RabL4s are novel proteins ...
129-287 2.09e-03

Rab GTPase-like family 4 (Rab-like4); RabL4 (Rab-like4) subfamily. RabL4s are novel proteins that have high sequence similarity with Rab family members, but display features that are distinct from Rabs, and have been termed Rab-like. As in other Rab-like proteins, RabL4 lacks a prenylation site at the C-terminus. The specific function of RabL4 remains unknown.


Pssm-ID: 206688 [Multi-domain]  Cd Length: 167  Bit Score: 39.82  E-value: 2.09e-03
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462612273 129 LKVGIVGNLSSGKSALVHRYLT-GTYVQEES--PEGGRF-KKEIVV--DGQSYLLLIRDEGGPPELQFAA---WVDAVVF 199
Cdd:cd04101     1 AQCAVVGDPAVGKSALVQMFHSdGATFQKNYtmTTGCDLvVKTVPVpdTSDSVELFIFDSAGQELFSDMVenvWEQPAVV 80
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462612273 200 --VFSLEDEISFQTVYNYFLRLCSFRNASEVPMVLVGTQDAISaaNPRVIDDSRARKLSTDlKRCTYYETCATYGLNVER 277
Cdd:cd04101    81 cvVYDVTNEVSFNNCSRWINRVRTHSHGLHTPGVLVGNKCDLT--DRREVDAAQAQALAQA-NTLKFYETSAKEGVGYEA 157
                         170
                  ....*....|
gi 2462612273 278 VFQDVAQKVV 287
Cdd:cd04101   158 PFLSLARAFH 167
Rab8_Rab10_Rab13_like cd01867
Rab GTPase families 8, 10, 13 (Rab8, Rab10, Rab13); Rab8/Sec4/Ypt2 are known or suspected to ...
130-286 3.07e-03

Rab GTPase families 8, 10, 13 (Rab8, Rab10, Rab13); Rab8/Sec4/Ypt2 are known or suspected to be involved in post-Golgi transport to the plasma membrane. It is likely that these Rabs have functions that are specific to the mammalian lineage and have no orthologs in plants. Rab8 modulates polarized membrane transport through reorganization of actin and microtubules, induces the formation of new surface extensions, and has an important role in directed membrane transport to cell surfaces. The Ypt2 gene of the fission yeast Schizosaccharomyces pombe encodes a member of the Ypt/Rab family of small GTP-binding proteins, related in sequence to Sec4p of Saccharomyces cerevisiae but closer to mammalian Rab8. 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: 206659 [Multi-domain]  Cd Length: 167  Bit Score: 39.17  E-value: 3.07e-03
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462612273 130 KVGIVGNLSSGKSALVHRY----LTGTYVqeeSPEGGRFK-KEIVVDGQSYLLLIRDEGGppELQFAAWVDA-------V 197
Cdd:cd01867     5 KLLLIGDSGVGKSCLLLRFsedsFNPSFI---STIGIDFKiRTIELDGKKIKLQIWDTAG--QERFRTITTSyyrgamgI 79
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462612273 198 VFVFSLEDEISFQTVYNYFLRLCsfRNASE-VPMVLVGTQDAIsaANPRVIDDSRARKLSTDLkRCTYYETCATYGLNVE 276
Cdd:cd01867    80 ILVYDITDEKSFENIKNWMRNID--EHASEdVERMLVGNKCDM--EEKRVVSKEEGEALAREY-GIKFLETSAKANINVE 154
                         170
                  ....*....|
gi 2462612273 277 RVFQDVAQKV 286
Cdd:cd01867   155 EAFLTLAKDI 164
PH cd00821
Pleckstrin homology (PH) domain; PH domains have diverse functions, but in general are ...
524-580 3.09e-03

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: 37.52  E-value: 3.09e-03
                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....*....
gi 2462612273 524 KKHRRKKSTGTPRPDGPSSATEEAEESFE--FVVVSLTGQTWHFEASTAEERELWVQSV 580
Cdd:cd00821    34 KKDSSYKPKGSIPLSGILEVEEVSPKERPhcFELVTPDGRTYYLQADSEEERQEWLKAL 92
PHA02875 PHA02875
ankyrin repeat protein; Provisional
736-822 4.22e-03

ankyrin repeat protein; Provisional


Pssm-ID: 165206 [Multi-domain]  Cd Length: 413  Bit Score: 40.36  E-value: 4.22e-03
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462612273 736 AVVEDDLRLLVMLLAHGSKEEVNETygdgDGRTALHLSSAMANVVFTQLLIWYGVDVRSRDARGLTPLAYARRAGSQECA 815
Cdd:PHA02875  109 ATILKKLDIMKLLIARGADPDIPNT----DKFSPLHLAVMMGDIKGIELLIDHKACLDIEDCCGCTPLIIAMAKGDIAIC 184

                  ....*..
gi 2462612273 816 DILIQHG 822
Cdd:PHA02875  185 KMLLDSG 191
PHA02875 PHA02875
ankyrin repeat protein; Provisional
732-832 5.75e-03

ankyrin repeat protein; Provisional


Pssm-ID: 165206 [Multi-domain]  Cd Length: 413  Bit Score: 39.97  E-value: 5.75e-03
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462612273 732 QLLRAVVEDDLRLLVMLLAHGskeevneTYGDG----DGRTALHLSSAMANVVFTQLLIWYGVDVRSRDARGLTPLAYAR 807
Cdd:PHA02875   71 ELHDAVEEGDVKAVEELLDLG-------KFADDvfykDGMTPLHLATILKKLDIMKLLIARGADPDIPNTDKFSPLHLAV 143
                          90       100
                  ....*....|....*....|....*...
gi 2462612273 808 RAGSQECADILIQH-GCPG--EGCGLAP 832
Cdd:PHA02875  144 MMGDIKGIELLIDHkACLDieDCCGCTP 171
 
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.
Help | Disclaimer | Write to the Help Desk
NCBI | NLM | NIH