NCBI Home Page NCBI Site Search page NCBI Guide that lists and describes the NCBI resources
Conserved domains on  [gi|7661962|ref|NP_055585.1|]
View 

arf-GAP with GTPase, ANK repeat and PH domain-containing protein 2 isoform PIKE-A [Homo sapiens]

Protein Classification

Centaurin_gamma and PH_AGAP domain-containing protein (domain architecture ID 10134854)

protein containing domains Centaurin_gamma, PH_AGAP, ArfGap, and ANK

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, ...
71-230 3.21e-96

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


:

Pssm-ID: 133303  Cd Length: 158  Bit Score: 300.56  E-value: 3.21e-96
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 7661962   71 LRLGVLGDARSGKSSLIHRFLTGSYQVLEKTESEQYKKEMLVDGQTHLVLIREEAGAPDAKFSGWADAVIFVFSLEDENS 150
Cdd:cd04103   1 LKLGIVGNLQSGKSALVHRYLTGSYVQLESPEGGRFKKEVLVDGQSHLLLIRDEGGAPDAQFASWVDAVIFVFSLENEAS 80
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 7661962  151 FQAVSRLHGQLSSLRgeGRGGLALALVGTQDRISASSPRVVGDARARALCADMKRCSYYETCATYGLNVDRVFQEVAQKV 230
Cdd:cd04103  81 FQTVYNLYHQLSSYR--NISEIPLILVGTQDAISESNPRVIDDARARQLCADMKRCSYYETCATYGLNVERVFQEAAQKI 158
PH_AGAP cd01250
Arf-GAP with GTPase, ANK repeat and PH domain-containing protein Pleckstrin homology (PH) ...
338-558 8.25e-56

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


:

Pssm-ID: 241281  Cd Length: 114  Bit Score: 188.68  E-value: 8.25e-56
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 7661962  338 RAIPIKQSFLLKRSGNSLNKEWKKKYVTLSSNGFLLYHPSINDYIHSTHGKEMDLLRTTVKVPGKRPPRAISAfgpsasi 417
Cdd:cd01250   1 RAIPIKQGYLYKRSSKSLNKEWKKKYVTLCDDGRLTYHPSLHDYMENVHGKEIDLLRTTVKVPGKRPPRASSK------- 73
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 7661962  418 nglvkdmstvqmgegleattpmpspspspsslqpppdqtskhllkpdrnlaralstdctpsgdlsplsrepppspmvkkq 497
Cdd:cd01250     --------------------------------------------------------------------------------
                       170       180       190       200       210       220
                ....*....|....*....|....*....|....*....|....*....|....*....|.
gi 7661962  498 rrkklttpsktegsagqaeeENFEFLIVSSTGQTWHFEAASFEERDAWVQAIESQILASLQ 558
Cdd:cd01250  74 --------------------SAFEFIIVSLDGKQWHFEAASSEERDEWVQAIEQQILASLQ 114
ArfGap pfam01412
Putative GTPase activating protein for Arf; Putative zinc fingers with GTPase activating ...
577-691 5.58e-53

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: 307528  Cd Length: 117  Bit Score: 180.90  E-value: 5.58e-53
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 7661962    577 AIQAIRNAKGNSICVDCGAPNPTWASLNLGALICIECSGIHRNLGTHLSRVRSLDLDDWPRELTLVLTAIGNDTANRVWE 656
Cdd:pfam01412   3 VLRELRKLPGNKVCADCGAPNPTWASLNLGIFICIRCSGVHRSLGVHISKVRSLTLDTWTPEQLEFMKAGGNDRANEYWE 82
                          90       100       110
                  ....*....|....*....|....*....|....*
gi 7661962    657 SDTRGRAKPSRDSSREERESWIRAKYEQLLFLAPL 691
Cdd:pfam01412  83 ANLPKPLPPPPSSDQEKRESFIRAKYVEKKFAEPE 117
ANK cd00204
ankyrin repeats; ankyrin repeats mediate protein-protein interactions in very diverse ...
702-791 1.92e-13

ankyrin repeats; ankyrin repeats mediate protein-protein interactions in very diverse families of proteins. The number of ANK repeats in a protein can range from 2 to over 20 (ankyrins, for example). ANK repeats may occur in combinations with other types of domains. The structural repeat unit contains two antiparallel helices and a beta-hairpin, repeats are stacked in a superhelical arrangement; this alignment contains 4 consecutive repeats.


:

Pssm-ID: 238125  Cd Length: 126  Bit Score: 69.33  E-value: 1.92e-13
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 7661962  702 LWAAVQAQDVATVLLLLahaRHGPlDTSVEDPQLRSPLHLAAELAHVVITQLLLWYGADVAARDAQGRTALFYARQAGSQ 781
Cdd:cd00204  11 LHLAASNGHLEVVKLLL---ENGA-DVNAKDNDGRTPLHLAAKNGHLEIVKLLLEKGADVNARDKDGNTPLHLAARNGNL 86
                        90
                ....*....|
gi 7661962  782 LCADILLQHG 791
Cdd:cd00204  87 DVVKLLLKHG 96
 
Name Accession Description Interval E-value
Centaurin_gamma cd04103
Centaurin gamma (CENTG) GTPase; The centaurins (alpha, beta, gamma, and delta) are large, ...
71-230 3.21e-96

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


Pssm-ID: 133303  Cd Length: 158  Bit Score: 300.56  E-value: 3.21e-96
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 7661962   71 LRLGVLGDARSGKSSLIHRFLTGSYQVLEKTESEQYKKEMLVDGQTHLVLIREEAGAPDAKFSGWADAVIFVFSLEDENS 150
Cdd:cd04103   1 LKLGIVGNLQSGKSALVHRYLTGSYVQLESPEGGRFKKEVLVDGQSHLLLIRDEGGAPDAQFASWVDAVIFVFSLENEAS 80
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 7661962  151 FQAVSRLHGQLSSLRgeGRGGLALALVGTQDRISASSPRVVGDARARALCADMKRCSYYETCATYGLNVDRVFQEVAQKV 230
Cdd:cd04103  81 FQTVYNLYHQLSSYR--NISEIPLILVGTQDAISESNPRVIDDARARQLCADMKRCSYYETCATYGLNVERVFQEAAQKI 158
PH_AGAP cd01250
Arf-GAP with GTPase, ANK repeat and PH domain-containing protein Pleckstrin homology (PH) ...
338-558 8.25e-56

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


Pssm-ID: 241281  Cd Length: 114  Bit Score: 188.68  E-value: 8.25e-56
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 7661962  338 RAIPIKQSFLLKRSGNSLNKEWKKKYVTLSSNGFLLYHPSINDYIHSTHGKEMDLLRTTVKVPGKRPPRAISAfgpsasi 417
Cdd:cd01250   1 RAIPIKQGYLYKRSSKSLNKEWKKKYVTLCDDGRLTYHPSLHDYMENVHGKEIDLLRTTVKVPGKRPPRASSK------- 73
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 7661962  418 nglvkdmstvqmgegleattpmpspspspsslqpppdqtskhllkpdrnlaralstdctpsgdlsplsrepppspmvkkq 497
Cdd:cd01250     --------------------------------------------------------------------------------
                       170       180       190       200       210       220
                ....*....|....*....|....*....|....*....|....*....|....*....|.
gi 7661962  498 rrkklttpsktegsagqaeeENFEFLIVSSTGQTWHFEAASFEERDAWVQAIESQILASLQ 558
Cdd:cd01250  74 --------------------SAFEFIIVSLDGKQWHFEAASSEERDEWVQAIEQQILASLQ 114
ArfGap pfam01412
Putative GTPase activating protein for Arf; Putative zinc fingers with GTPase activating ...
577-691 5.58e-53

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: 307528  Cd Length: 117  Bit Score: 180.90  E-value: 5.58e-53
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 7661962    577 AIQAIRNAKGNSICVDCGAPNPTWASLNLGALICIECSGIHRNLGTHLSRVRSLDLDDWPRELTLVLTAIGNDTANRVWE 656
Cdd:pfam01412   3 VLRELRKLPGNKVCADCGAPNPTWASLNLGIFICIRCSGVHRSLGVHISKVRSLTLDTWTPEQLEFMKAGGNDRANEYWE 82
                          90       100       110
                  ....*....|....*....|....*....|....*
gi 7661962    657 SDTRGRAKPSRDSSREERESWIRAKYEQLLFLAPL 691
Cdd:pfam01412  83 ANLPKPLPPPPSSDQEKRESFIRAKYVEKKFAEPE 117
ArfGap smart00105
Putative GTP-ase activating proteins for the small GTPase, ARF; Putative zinc fingers with ...
578-695 3.64e-52

Putative GTP-ase activating proteins for the small GTPase, ARF; Putative zinc fingers with GTPase activating proteins (GAPs) towards the small GTPase, Arf. The GAP of ARD1 stimulates GTPase hydrolysis for ARD1 but not ARFs.


Pssm-ID: 214518  Cd Length: 119  Bit Score: 178.69  E-value: 3.64e-52
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 7661962     578 IQAIRNAKGNSICVDCGAPNPTWASLNLGALICIECSGIHRNLGTHLSRVRSLDLDDWPRELTLVLTAIGNDTANRVWES 657
Cdd:smart00105   1 LKLLRSIPGNKKCFDCGAPNPTWASVNLGVFLCIECSGIHRSLGVHISKVRSLTLDTWTEEELRLLQKGGNENANSIWES 80
                           90       100       110
                   ....*....|....*....|....*....|....*....
gi 7661962     658 DTRGRAKPSRDSS-REERESWIRAKYEQLLFLAPLSTSE 695
Cdd:smart00105  81 NLDDFSLKPPDDDdQQKYESFIAAKYEEKLFVPPESAEE 119
COG5347 COG5347
GTPase-activating protein that regulates ARFs (ADP-ribosylation factors), involved in ...
570-722 8.29e-33

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


Pssm-ID: 227651  Cd Length: 319  Bit Score: 130.67  E-value: 8.29e-33
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 7661962  570 DSQSEAVAIQAIRNAKGNSICVDCGAPNPTWASLNLGALICIECSGIHRNLGTHLSRVRSLDLDDWPRELTLVLTAIGND 649
Cdd:COG5347   3 TKSEDRKLLKLLKSDSSNKKCADCGAPNPTWASVNLGVFLCIDCAGVHRSLGVHISKVKSLTLDNWTEEELRRMEVGGNS 82
                        90       100       110       120       130       140       150
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 7661962  650 TANRVWESD-TRGRAKPSR-DSSREERESWIRAKYEQLLFLAPLSTSEEPLGRQLWAAVQAQDVATVLLLLAHAR 722
Cdd:COG5347  83 NANRFYEKNlLDQLLLPIKaKYDSSVAKKYIRKKYELKKFIDDSSSPSDFSSFSASSTRTVDSVDDRLDSESQSR 157
PLN03114 PLN03114
ADP-ribosylation factor GTPase-activating protein AGD10; Provisional
587-651 1.19e-15

ADP-ribosylation factor GTPase-activating protein AGD10; Provisional


Pssm-ID: 178661  Cd Length: 395  Bit Score: 79.90  E-value: 1.19e-15
                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 7661962   587 NSICVDCGAPNPTWASLNLGALICIECSGIHRNLGTHLSRVRSLDLDDWPRELTLVLTAIGNDTA 651
Cdd:PLN03114  22 NKICFDCNAKNPTWASVTYGIFLCIDCSAVHRSLGVHISFVRSTNLDSWSSEQLKMMIYGGNNRA 86
small_GTPase smart00010
Small GTPase of the Ras superfamily; ill-defined subfamily; SMART predicts Ras-like small ...
69-236 1.38e-13

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


Pssm-ID: 197466  Cd Length: 166  Bit Score: 70.67  E-value: 1.38e-13
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 7661962      69 PELRLGVLGDARSGKSSLIHRFLTGSYqvLEK---TESEQYKKEMLVDGQTHLVLIREEAGapDAKFSGWAD-------A 138
Cdd:smart00010   1 REYKLVVLGGGGVGKSALTIQFVQGHF--VDEydpTIEDSYRKQIEIDGEVCLLDILDTAG--QEEFSAMRDqymrtgeG 76
                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 7661962     139 VIFVFSLEDENSFQAVSRLHGQLssLRGEGRGGLALALVGTQ-DRISAsspRVVGDARARALCADMKrCSYYETCATYGL 217
Cdd:smart00010  77 FLLVYSITDRQSFEEIAKFREQI--LRVKDRDDVPIVLVGNKcDLENE---RVVSTEEGKELARQWG-CPFLETSAKERI 150
                          170
                   ....*....|....*....
gi 7661962     218 NVDRVFQEVaqkVVTLRKQ 236
Cdd:smart00010 151 NVDEAFYDL---VREIRKS 166
ANK cd00204
ankyrin repeats; ankyrin repeats mediate protein-protein interactions in very diverse ...
702-791 1.92e-13

ankyrin repeats; ankyrin repeats mediate protein-protein interactions in very diverse families of proteins. The number of ANK repeats in a protein can range from 2 to over 20 (ankyrins, for example). ANK repeats may occur in combinations with other types of domains. The structural repeat unit contains two antiparallel helices and a beta-hairpin, repeats are stacked in a superhelical arrangement; this alignment contains 4 consecutive repeats.


Pssm-ID: 238125  Cd Length: 126  Bit Score: 69.33  E-value: 1.92e-13
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 7661962  702 LWAAVQAQDVATVLLLLahaRHGPlDTSVEDPQLRSPLHLAAELAHVVITQLLLWYGADVAARDAQGRTALFYARQAGSQ 781
Cdd:cd00204  11 LHLAASNGHLEVVKLLL---ENGA-DVNAKDNDGRTPLHLAAKNGHLEIVKLLLEKGADVNARDKDGNTPLHLAARNGNL 86
                        90
                ....*....|
gi 7661962  782 LCADILLQHG 791
Cdd:cd00204  87 DVVKLLLKHG 96
Ras pfam00071
Ras family; Includes sub-families Ras, Rab, Rac, Ral, Ran, Rap Ypt1 and more. Shares P-loop ...
75-230 7.40e-13

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


Pssm-ID: 306559  Cd Length: 162  Bit Score: 68.30  E-value: 7.40e-13
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 7661962     75 VLGDARSGKSSLIHRFLTGSYQvlEKTES----EQYKKEMLVDGQTHLVLIREEAGA------PDAKFSGwADAVIFVFS 144
Cdd:pfam00071   4 LVGDGGVGKSSLLIRFTQNKFP--EEYIPtigvDFYTKTVEVDGKTVKLQIWDTAGQerfralRPLYYRG-ADGFLLVYD 80
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 7661962    145 LEDENSFQAVSRLHGQLSSLRGEgrgGLALALVGTQdrISASSPRVVGDARARALCADMKrCSYYETCATYGLNVDRVFQ 224
Cdd:pfam00071  81 ITSRDSFENVKKWVEEILRHADE---NVPIVLVGNK--CDLEDQRVVSTEEGEALAKELG-LPFMETSAKTNENVEEAFE 154

                  ....*.
gi 7661962    225 EVAQKV 230
Cdd:pfam00071 155 ELAREI 160
Ank_2 pfam12796
Ankyrin repeats (3 copies);
702-792 4.04e-10

Ankyrin repeats (3 copies);


Pssm-ID: 315466  Cd Length: 92  Bit Score: 58.97  E-value: 4.04e-10
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 7661962    702 LWAAVQAQDVATVLLLLAHarhgPLDTSVEDPQLRSPLHLAAELAHVVITQLLLWYgADVAARDAQGRTALFYARQAGSQ 781
Cdd:pfam12796   1 LHLAAKNGDLELVKLLLEE----GADANLQDKNGRTALHLAAKNGHLEIVKLLLEH-ADVNLKDKNGRTALHYAARSGHL 75
                          90
                  ....*....|.
gi 7661962    782 LCADILLQHGC 792
Cdd:pfam12796  76 EIVKLLLEKGA 86
PLN03118 PLN03118
Rab family protein; Provisional
75-231 2.24e-06

Rab family protein; Provisional


Pssm-ID: 215587  Cd Length: 211  Bit Score: 49.28  E-value: 2.24e-06
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 7661962    75 VLGDARSGKSSLIHRFLTGSYQVLEKTESEQYK-KEMLVDGQTHLVLIREEAGAP-----DAKFSGWADAVIFVFSLEDE 148
Cdd:PLN03118  19 LIGDSGVGKSSLLVSFISSSVEDLAPTIGVDFKiKQLTVGGKRLKLTIWDTAGQErfrtlTSSYYRNAQGIILVYDVTRR 98
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 7661962   149 NSFQAVSRLHGQLSSLRGEGRGGLALaLVGtqDRISASSPRVVGDARARALcADMKRCSYYETCATYGLNVDRVFQEVAQ 228
Cdd:PLN03118  99 ETFTNLSDVWGKEVELYSTNQDCVKM-LVG--NKVDRESERDVSREEGMAL-AKEHGCLFLECSAKTRENVEQCFEELAL 174

                 ...
gi 7661962   229 KVV 231
Cdd:PLN03118 175 KIM 177
PTZ00322 PTZ00322
6-phosphofructo-2-kinase/fructose-2,6-biphosphatase; Provisional
724-797 2.28e-05

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


Pssm-ID: 140343  Cd Length: 664  Bit Score: 47.97  E-value: 2.28e-05
                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 7661962   724 GPLDTSVEDPQLRSPLHLAAELAHVVITQLLLWYGADVAARDAQGRTALFYARQAGSQLCADILLQHG-CPGEGG 797
Cdd:PTZ00322 104 GGADPNCRDYDGRTPLHIACANGHVQVVRVLLEFGADPTLLDKDGKTPLELAEENGFREVVQLLSRHSqCHFELG 178
Gem1 COG1100
GTPase SAR1 family domain [General function prediction only];
69-239 4.35e-05

GTPase SAR1 family domain [General function prediction only];


Pssm-ID: 224025  Cd Length: 219  Bit Score: 45.34  E-value: 4.35e-05
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 7661962   69 PELRLGVLGDARSGKSSLIHRFLTGSY-QVLEKTESEQY-KKEMLVDGQTHLVLIREEAGAPDAK------FSGwADAVI 140
Cdd:COG1100   4 KEFKIVVLGDGGVGKTTLLNRLVGDEFpEGYPPTIGNLDpAKTIEPYRRNIKLQLWDTAGQEEYRslrpeyYRG-ANGIL 82
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 7661962  141 FVFSLED-ENSFQAVSRLHGQLSSLRGEgrgGLALALVGTQ----DRISASSPRVVGDARARALCADMKRC--------S 207
Cdd:COG1100  83 IVYDSTLrESSDELTEEWLEELRELAPD---DVPILLVGNKidlfDEQSSSEEILNQLNREVVLLVLAPKAvlpevanpA 159
                       170       180       190
                ....*....|....*....|....*....|....
gi 7661962  208 YYETCATY--GLNVDRVFQEVAQKVVTLRKQQQL 239
Cdd:COG1100 160 LLETSAKSltGPNVNELFKELLRKLLEEIEKLVL 193
PH smart00233
Pleckstrin homology domain; Domain commonly found in eukaryotic signalling proteins. The ...
508-553 5.22e-05

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


Pssm-ID: 214574  Cd Length: 102  Bit Score: 43.69  E-value: 5.22e-05
                           10        20        30        40
                   ....*....|....*....|....*....|....*....|....*.
gi 7661962     508 TEGSAGQAEEENFEFLIVSSTGQTWHFEAASFEERDAWVQAIESQI 553
Cdd:smart00233  56 REAPDPDSSKKPHCFEIKTSDRKTLLLQAESEEEREKWVEALRKAI 101
ANKYR COG0666
Ankyrin repeat [Signal transduction mechanisms];
703-791 3.09e-04

Ankyrin repeat [Signal transduction mechanisms];


Pssm-ID: 223738  Cd Length: 235  Bit Score: 43.27  E-value: 3.09e-04
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 7661962  703 WAAVQAQDVA----TVLLLLAHARHGPLDTsVEDPQLRSPLHLAAELAHVVITQLLLWYGADVAARDAQGRTALFYARQA 778
Cdd:COG0666 112 LAALNGNPPEgnieVAKLLLEAGADLDVNN-LRDEDGNTPLHWAALNGDADIVELLLEAGADPNSRNSYGVTALDPAAKN 190
                        90
                ....*....|...
gi 7661962  779 GSQLCADILLQHG 791
Cdd:COG0666 191 GRIELVKLLLDKG 203
 
Name Accession Description Interval E-value
Centaurin_gamma cd04103
Centaurin gamma (CENTG) GTPase; The centaurins (alpha, beta, gamma, and delta) are large, ...
71-230 3.21e-96

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


Pssm-ID: 133303  Cd Length: 158  Bit Score: 300.56  E-value: 3.21e-96
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 7661962   71 LRLGVLGDARSGKSSLIHRFLTGSYQVLEKTESEQYKKEMLVDGQTHLVLIREEAGAPDAKFSGWADAVIFVFSLEDENS 150
Cdd:cd04103   1 LKLGIVGNLQSGKSALVHRYLTGSYVQLESPEGGRFKKEVLVDGQSHLLLIRDEGGAPDAQFASWVDAVIFVFSLENEAS 80
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 7661962  151 FQAVSRLHGQLSSLRgeGRGGLALALVGTQDRISASSPRVVGDARARALCADMKRCSYYETCATYGLNVDRVFQEVAQKV 230
Cdd:cd04103  81 FQTVYNLYHQLSSYR--NISEIPLILVGTQDAISESNPRVIDDARARQLCADMKRCSYYETCATYGLNVERVFQEAAQKI 158
PH_AGAP cd01250
Arf-GAP with GTPase, ANK repeat and PH domain-containing protein Pleckstrin homology (PH) ...
338-558 8.25e-56

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


Pssm-ID: 241281  Cd Length: 114  Bit Score: 188.68  E-value: 8.25e-56
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 7661962  338 RAIPIKQSFLLKRSGNSLNKEWKKKYVTLSSNGFLLYHPSINDYIHSTHGKEMDLLRTTVKVPGKRPPRAISAfgpsasi 417
Cdd:cd01250   1 RAIPIKQGYLYKRSSKSLNKEWKKKYVTLCDDGRLTYHPSLHDYMENVHGKEIDLLRTTVKVPGKRPPRASSK------- 73
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 7661962  418 nglvkdmstvqmgegleattpmpspspspsslqpppdqtskhllkpdrnlaralstdctpsgdlsplsrepppspmvkkq 497
Cdd:cd01250     --------------------------------------------------------------------------------
                       170       180       190       200       210       220
                ....*....|....*....|....*....|....*....|....*....|....*....|.
gi 7661962  498 rrkklttpsktegsagqaeeENFEFLIVSSTGQTWHFEAASFEERDAWVQAIESQILASLQ 558
Cdd:cd01250  74 --------------------SAFEFIIVSLDGKQWHFEAASSEERDEWVQAIEQQILASLQ 114
ArfGap pfam01412
Putative GTPase activating protein for Arf; Putative zinc fingers with GTPase activating ...
577-691 5.58e-53

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: 307528  Cd Length: 117  Bit Score: 180.90  E-value: 5.58e-53
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 7661962    577 AIQAIRNAKGNSICVDCGAPNPTWASLNLGALICIECSGIHRNLGTHLSRVRSLDLDDWPRELTLVLTAIGNDTANRVWE 656
Cdd:pfam01412   3 VLRELRKLPGNKVCADCGAPNPTWASLNLGIFICIRCSGVHRSLGVHISKVRSLTLDTWTPEQLEFMKAGGNDRANEYWE 82
                          90       100       110
                  ....*....|....*....|....*....|....*
gi 7661962    657 SDTRGRAKPSRDSSREERESWIRAKYEQLLFLAPL 691
Cdd:pfam01412  83 ANLPKPLPPPPSSDQEKRESFIRAKYVEKKFAEPE 117
ArfGap smart00105
Putative GTP-ase activating proteins for the small GTPase, ARF; Putative zinc fingers with ...
578-695 3.64e-52

Putative GTP-ase activating proteins for the small GTPase, ARF; Putative zinc fingers with GTPase activating proteins (GAPs) towards the small GTPase, Arf. The GAP of ARD1 stimulates GTPase hydrolysis for ARD1 but not ARFs.


Pssm-ID: 214518  Cd Length: 119  Bit Score: 178.69  E-value: 3.64e-52
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 7661962     578 IQAIRNAKGNSICVDCGAPNPTWASLNLGALICIECSGIHRNLGTHLSRVRSLDLDDWPRELTLVLTAIGNDTANRVWES 657
Cdd:smart00105   1 LKLLRSIPGNKKCFDCGAPNPTWASVNLGVFLCIECSGIHRSLGVHISKVRSLTLDTWTEEELRLLQKGGNENANSIWES 80
                           90       100       110
                   ....*....|....*....|....*....|....*....
gi 7661962     658 DTRGRAKPSRDSS-REERESWIRAKYEQLLFLAPLSTSE 695
Cdd:smart00105  81 NLDDFSLKPPDDDdQQKYESFIAAKYEEKLFVPPESAEE 119
COG5347 COG5347
GTPase-activating protein that regulates ARFs (ADP-ribosylation factors), involved in ...
570-722 8.29e-33

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


Pssm-ID: 227651  Cd Length: 319  Bit Score: 130.67  E-value: 8.29e-33
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 7661962  570 DSQSEAVAIQAIRNAKGNSICVDCGAPNPTWASLNLGALICIECSGIHRNLGTHLSRVRSLDLDDWPRELTLVLTAIGND 649
Cdd:COG5347   3 TKSEDRKLLKLLKSDSSNKKCADCGAPNPTWASVNLGVFLCIDCAGVHRSLGVHISKVKSLTLDNWTEEELRRMEVGGNS 82
                        90       100       110       120       130       140       150
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 7661962  650 TANRVWESD-TRGRAKPSR-DSSREERESWIRAKYEQLLFLAPLSTSEEPLGRQLWAAVQAQDVATVLLLLAHAR 722
Cdd:COG5347  83 NANRFYEKNlLDQLLLPIKaKYDSSVAKKYIRKKYELKKFIDDSSSPSDFSSFSASSTRTVDSVDDRLDSESQSR 157
Ras cd00876
Rat sarcoma (Ras) family of small guanosine triphosphatases (GTPases); The Ras family of the ...
72-230 4.98e-19

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  Cd Length: 160  Bit Score: 86.81  E-value: 4.98e-19
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 7661962   72 RLGVLGDARSGKSSLIHRFLTGSYQVL-EKTESEQYKKEMLVDGQT-HLVLI----REEAGAPDAKFSGWADAVIFVFSL 145
Cdd:cd00876   1 KLVVLGAGGVGKSALTIRFVSGEFVEEyDPTIEDSYRKQIVVDGETyTLDILdtagQEEFSAMRDQYIRNGDGFILVYSI 80
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 7661962  146 EDENSFQAVSRLHGQLSSLRGEGRggLALALVGtqDRISASSPRVVGDARARALcADMKRCSYYETCATYGLNVDRVFQE 225
Cdd:cd00876  81 TSRESFEEIKNIREQILRVKDKED--VPIVLVG--NKCDLENERQVSTEEGEAL-AEEWGCPFLETSAKTNINIDELFNT 155

                ....*
gi 7661962  226 VAQKV 230
Cdd:cd00876 156 LVREI 160
PLN03114 PLN03114
ADP-ribosylation factor GTPase-activating protein AGD10; Provisional
587-651 1.19e-15

ADP-ribosylation factor GTPase-activating protein AGD10; Provisional


Pssm-ID: 178661  Cd Length: 395  Bit Score: 79.90  E-value: 1.19e-15
                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 7661962   587 NSICVDCGAPNPTWASLNLGALICIECSGIHRNLGTHLSRVRSLDLDDWPRELTLVLTAIGNDTA 651
Cdd:PLN03114  22 NKICFDCNAKNPTWASVTYGIFLCIDCSAVHRSLGVHISFVRSTNLDSWSSEQLKMMIYGGNNRA 86
RERG_RasL11_like cd04146
Ras-related and Estrogen-Regulated Growth inhibitor (RERG) and Ras-like 11 (RasL11)-like ...
73-230 1.07e-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  Cd Length: 166  Bit Score: 71.15  E-value: 1.07e-13
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 7661962   73 LGVLGDARSGKSSLIHRFLT----GSYqvlEKTESEQYKKEMLVDGQTHLVLIREEAG--APDAKFS-----GWADAVIF 141
Cdd:cd04146   2 IAVLGASGVGKSALTVRFLTkrfiGEY---EPNLESLYSRQVTIDGEQVSLEIQDTPGqqQNEDPESlerslRWADGFVL 78
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 7661962  142 VFSLEDENSFQAVSRLHGQLSSLRGEGrGGLALALVGT-QDRISAsspRVVGDARARALcADMKRCSYYE--TCATYgLN 218
Cdd:cd04146  79 VYSITDRSSFDVVSQLLQLIREIKKRD-GEIPVILVGNkADLLHS---RQVSTEEGQKL-ALELGCLFFEvsAAENY-LE 152
                       170
                ....*....|..
gi 7661962  219 VDRVFQEVAQKV 230
Cdd:cd04146 153 VQNVFHELCREV 164
small_GTPase smart00010
Small GTPase of the Ras superfamily; ill-defined subfamily; SMART predicts Ras-like small ...
69-236 1.38e-13

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


Pssm-ID: 197466  Cd Length: 166  Bit Score: 70.67  E-value: 1.38e-13
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 7661962      69 PELRLGVLGDARSGKSSLIHRFLTGSYqvLEK---TESEQYKKEMLVDGQTHLVLIREEAGapDAKFSGWAD-------A 138
Cdd:smart00010   1 REYKLVVLGGGGVGKSALTIQFVQGHF--VDEydpTIEDSYRKQIEIDGEVCLLDILDTAG--QEEFSAMRDqymrtgeG 76
                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 7661962     139 VIFVFSLEDENSFQAVSRLHGQLssLRGEGRGGLALALVGTQ-DRISAsspRVVGDARARALCADMKrCSYYETCATYGL 217
Cdd:smart00010  77 FLLVYSITDRQSFEEIAKFREQI--LRVKDRDDVPIVLVGNKcDLENE---RVVSTEEGKELARQWG-CPFLETSAKERI 150
                          170
                   ....*....|....*....
gi 7661962     218 NVDRVFQEVaqkVVTLRKQ 236
Cdd:smart00010 151 NVDEAFYDL---VREIRKS 166
ANK cd00204
ankyrin repeats; ankyrin repeats mediate protein-protein interactions in very diverse ...
702-791 1.92e-13

ankyrin repeats; ankyrin repeats mediate protein-protein interactions in very diverse families of proteins. The number of ANK repeats in a protein can range from 2 to over 20 (ankyrins, for example). ANK repeats may occur in combinations with other types of domains. The structural repeat unit contains two antiparallel helices and a beta-hairpin, repeats are stacked in a superhelical arrangement; this alignment contains 4 consecutive repeats.


Pssm-ID: 238125  Cd Length: 126  Bit Score: 69.33  E-value: 1.92e-13
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 7661962  702 LWAAVQAQDVATVLLLLahaRHGPlDTSVEDPQLRSPLHLAAELAHVVITQLLLWYGADVAARDAQGRTALFYARQAGSQ 781
Cdd:cd00204  11 LHLAASNGHLEVVKLLL---ENGA-DVNAKDNDGRTPLHLAAKNGHLEIVKLLLEKGADVNARDKDGNTPLHLAARNGNL 86
                        90
                ....*....|
gi 7661962  782 LCADILLQHG 791
Cdd:cd00204  87 DVVKLLLKHG 96
Rap_like cd04136
Rap-like family consists of Rap1, Rap2 and RSR1; The Rap subfamily consists of the Rap1, Rap2, ...
70-230 2.68e-13

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  Cd Length: 164  Bit Score: 69.90  E-value: 2.68e-13
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 7661962   70 ELRLGVLGDARSGKSSLIHRFLTGSYqvLEK---TESEQYKKEMLVDGQTHLVLIREEAGApdAKFSGWAD-------AV 139
Cdd:cd04136   1 EYKLVVLGSGGVGKSALTVQFVQGIF--VDKydpTIEDSYRKQIEVDCQQCMLEILDTAGT--EQFTAMRDlyikngqGF 76
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 7661962  140 IFVFSLEDENSFQAVSRLHGQLssLRGEGRGGLALALVGtqDRISASSPRVVGDARARALCADMKRCSYYETCATYGLNV 219
Cdd:cd04136  77 ALVYSITAQQSFNDLQDLREQI--LRVKDTEDVPMILVG--NKCDLEDERVVSKEEGQNLARQWGNCPFLETSAKSKINV 152
                       170
                ....*....|.
gi 7661962  220 DRVFQEVAQKV 230
Cdd:cd04136 153 DEIFYDLVRQI 163
ANK cd00204
ankyrin repeats; ankyrin repeats mediate protein-protein interactions in very diverse ...
702-788 4.56e-13

ankyrin repeats; ankyrin repeats mediate protein-protein interactions in very diverse families of proteins. The number of ANK repeats in a protein can range from 2 to over 20 (ankyrins, for example). ANK repeats may occur in combinations with other types of domains. The structural repeat unit contains two antiparallel helices and a beta-hairpin, repeats are stacked in a superhelical arrangement; this alignment contains 4 consecutive repeats.


Pssm-ID: 238125  Cd Length: 126  Bit Score: 68.18  E-value: 4.56e-13
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 7661962  702 LWAAVQAQDVATVLLLLahaRHGPlDTSVEDPQLRSPLHLAAELAHVVITQLLLWYGADVAARDAQGRTALFYARQAGSQ 781
Cdd:cd00204  44 LHLAAKNGHLEIVKLLL---EKGA-DVNARDKDGNTPLHLAARNGNLDVVKLLLKHGADVNARDKDGRTPLHLAAKNGHL 119

                ....*..
gi 7661962  782 LCADILL 788
Cdd:cd00204 120 EVVKLLL 126
RAS smart00173
Ras subfamily of RAS small GTPases; Similar in fold and function to the bacterial EF-Tu GTPase. ...
72-226 4.58e-13

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  Cd Length: 164  Bit Score: 69.12  E-value: 4.58e-13
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 7661962      72 RLGVLGDARSGKSSLIHRFLTGSYqvLEK---TESEQYKKEMLVDGQTHLVLIREEAGapDAKFSGWAD-------AVIF 141
Cdd:smart00173   2 KLVVLGSGGVGKSALTIQFIQGHF--VDDydpTIEDSYRKQIEIDGEVCLLDILDTAG--QEEFSAMRDqymrtgeGFLL 77
                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 7661962     142 VFSLEDENSFQAVSRLHGQLssLRGEGRGGLALALVGTQ-DRISAsspRVVGDARARALCADMKrCSYYETCATYGLNVD 220
Cdd:smart00173  78 VYSITDRQSFEEIKKFREQI--LRVKDRDDVPIVLVGNKcDLESE---RVVSTEEGKELARQWG-CPFLETSAKERVNVD 151

                   ....*.
gi 7661962     221 RVFQEV 226
Cdd:smart00173 152 EAFYDL 157
Ras pfam00071
Ras family; Includes sub-families Ras, Rab, Rac, Ral, Ran, Rap Ypt1 and more. Shares P-loop ...
75-230 7.40e-13

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


Pssm-ID: 306559  Cd Length: 162  Bit Score: 68.30  E-value: 7.40e-13
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 7661962     75 VLGDARSGKSSLIHRFLTGSYQvlEKTES----EQYKKEMLVDGQTHLVLIREEAGA------PDAKFSGwADAVIFVFS 144
Cdd:pfam00071   4 LVGDGGVGKSSLLIRFTQNKFP--EEYIPtigvDFYTKTVEVDGKTVKLQIWDTAGQerfralRPLYYRG-ADGFLLVYD 80
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 7661962    145 LEDENSFQAVSRLHGQLSSLRGEgrgGLALALVGTQdrISASSPRVVGDARARALCADMKrCSYYETCATYGLNVDRVFQ 224
Cdd:pfam00071  81 ITSRDSFENVKKWVEEILRHADE---NVPIVLVGNK--CDLEDQRVVSTEEGEALAKELG-LPFMETSAKTNENVEEAFE 154

                  ....*.
gi 7661962    225 EVAQKV 230
Cdd:pfam00071 155 ELAREI 160
Rab cd00154
Ras-related in brain (Rab) family of small guanosine triphosphatases (GTPases); Rab GTPases ...
71-228 7.59e-13

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


Pssm-ID: 206640  Cd Length: 159  Bit Score: 68.25  E-value: 7.59e-13
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 7661962   71 LRLGVLGDARSGKSSLIHRFLTGSYQvlEKTES----EQYKKEMLVDGQTHLVLIREEAGapDAKFS--------GwADA 138
Cdd:cd00154   1 FKIVLIGDSGVGKTSLLLRFVDNKFS--ENYKStigvDFKSKTIEVDGKKVKLQIWDTAG--QERFRsitssyyrG-AHG 75
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 7661962  139 VIFVFSLEDENSFQAVSRLhgqLSSLRGEGRGGLALALVGTqdRISASSPRVVGDARARALCADMKrCSYYETCATYGLN 218
Cdd:cd00154  76 AILVYDVTNRESFENLDKW---LNELKEYAPPNIPIILVGN--KSDLEDERQVSTEEAQQFAKENG-LLFFETSAKTGEN 149
                       170
                ....*....|
gi 7661962  219 VDRVFQEVAQ 228
Cdd:cd00154 150 VDEAFESLAR 159
Ras_like_GTPase cd00882
Rat sarcoma (Ras)-like superfamily of small guanosine triphosphatases (GTPases); Ras-like ...
74-228 1.00e-12

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


Pssm-ID: 206648  Cd Length: 161  Bit Score: 67.87  E-value: 1.00e-12
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 7661962   74 GVLGDARSGKSSLIHRFLTGSY----QVLEKTESEQYKKeMLVDGQTHLVLIREEAGAPDAKFSG----------WADAV 139
Cdd:cd00882   1 VVVGRGGVGKSSLLNALLGGEVgevsDVPGTTRDPDVYV-KELDKGKVKLVLVDTPGLDEFGGLGreelarlllrGADLI 79
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 7661962  140 IFVFSLEDENSFQAVsrlhgQLSSLRGEGRGGLALALVGTQ-DRISASSPRVVGDARARALcadMKRCSYYETCATYGLN 218
Cdd:cd00882  80 LLVVDSTDRESEEDA-----KLLILRRLRKEGIPIILVGNKiDLLEEREVEELLRLEELAK---ILGVPVFEVSAKTGEG 151
                       170
                ....*....|
gi 7661962  219 VDRVFQEVAQ 228
Cdd:cd00882 152 VDELFEKLIE 161
Rab7 cd01862
Rab GTPase family 7 (Rab7); Rab7 subfamily. Rab7 is a small Rab GTPase that regulates ...
71-236 1.26e-12

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


Pssm-ID: 206655  Cd Length: 172  Bit Score: 67.69  E-value: 1.26e-12
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 7661962   71 LRLGVLGDARSGKSSLIHRFLTgsyqvleKTESEQYK---------KEMLVDGQTHLVLIREEAGAPD------AKFSGw 135
Cdd:cd01862   1 LKVIILGDSGVGKTSLMNQYVN-------KKFSNQYKatigadfltKEVTVDDRLVTLQIWDTAGQERfqslgvAFYRG- 72
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 7661962  136 ADAVIFVFSLEDENSFQAVSRLHGQ-LSSLRGEGRGGLALALVGtqDRISASSPRVVGDARARALCADMKRCSYYETCAT 214
Cdd:cd01862  73 ADCCVLVYDVTNPKSFESLDSWRDEfLIQASPRDPENFPFVVLG--NKIDLEEKRQVSTKKAQQWCKSKGNIPYFETSAK 150
                       170       180
                ....*....|....*....|..
gi 7661962  215 YGLNVDRVFQEVAQKVVTLRKQ 236
Cdd:cd01862 151 EAINVDQAFETIARLALEQEKE 172
Rap2 cd04176
Rap2 family GTPase consists of Rap2a, Rap2b, and Rap2c; The Rap2 subgroup is part of the Rap ...
70-230 1.67e-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  Cd Length: 163  Bit Score: 67.17  E-value: 1.67e-12
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 7661962   70 ELRLGVLGDARSGKSSLIHRFLTGSYqvLEK---TESEQYKKEMLVDGQTHLVLIREEAGApdAKFSGWAD-------AV 139
Cdd:cd04176   1 EYKVVVLGSGGVGKSALTVQFVSGTF--IEKydpTIEDFYRKEIEVDSSPSVLEILDTAGT--EQFASMRDlyikngqGF 76
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 7661962  140 IFVFSLEDENSFQAVSRLHGQLssLRGEGRGGLALALVGtqDRISASSPRVVGDARARALcADMKRCSYYETCATYGLNV 219
Cdd:cd04176  77 IVVYSLVNQQTFQDIKPMRDQI--VRVKGYEKVPIILVG--NKVDLESEREVSSAEGRAL-AEEWGCPFMETSAKSKTMV 151
                       170
                ....*....|.
gi 7661962  220 DRVFQEVAQKV 230
Cdd:cd04176 152 NELFAEIVRQM 162
RAB smart00175
Rab subfamily of small GTPases; Rab GTPases are implicated in vesicle trafficking.
71-231 4.34e-12

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


Pssm-ID: 197555  Cd Length: 164  Bit Score: 65.99  E-value: 4.34e-12
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 7661962      71 LRLGVLGDARSGKSSLIHRFLTGSYqvlekteSEQYK---------KEMLVDGQTHLVLIREEAGAP------DAKFSGw 135
Cdd:smart00175   1 FKIILIGDSGVGKSSLLSRFTDGKF-------SEQYKstigvdfktKTIEVDGKRVKLQIWDTAGQErfrsitSSYYRG- 72
                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 7661962     136 ADAVIFVFSLEDENSFQAVSRLhgqLSSLRGEGRGGLALALVGTqdRISASSPRVVGDARARALCADmKRCSYYETCATY 215
Cdd:smart00175  73 AVGALLVYDITNRESFENLENW---LKELREYASPNVVIMLVGN--KSDLEEQRQVSREEAEAFAEE-HGLPFFETSAKT 146
                          170
                   ....*....|....*.
gi 7661962     216 GLNVDRVFQEVAQKVV 231
Cdd:smart00175 147 NTNVEEAFEELAREIL 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, ...
69-230 5.22e-12

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  Cd Length: 164  Bit Score: 65.89  E-value: 5.22e-12
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 7661962   69 PELRLGVLGDARSGKSSLIHRFLTgSYQVLE--KTESEQYKKEMLVDGQ-THLVLI----REEAGAPDAKFSGWADAVIF 141
Cdd:cd04145   1 PTYKLVVVGGGGVGKSALTIQFIQ-SYFVTDydPTIEDSYTKQCEIDGQwAILDILdtagQEEFSAMREQYMRTGEGFLL 79
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 7661962  142 VFSLEDENSFQAVSRLHGQLssLRGEGRGGLALALVGtqDRISASSPRVVGDARARALCADMKrCSYYETCATYGLNVDR 221
Cdd:cd04145  80 VFSVTDRGSFEEVDKFHTQI--LRVKDRDEFPMILVG--NKADLEHQRKVSREEGQELARKLK-IPYIETSAKDRLNVDK 154

                ....*....
gi 7661962  222 VFQEVAQKV 230
Cdd:cd04145 155 AFHDLVRVI 163
Ras2 cd04144
Rat sarcoma (Ras) family 2 of small guanosine triphosphatases (GTPases); The Ras2 subfamily, ...
72-238 1.51e-11

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


Pssm-ID: 133344  Cd Length: 190  Bit Score: 64.48  E-value: 1.51e-11
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 7661962   72 RLGVLGDARSGKSSLIHRFLTGSY-QVLEKTESEQYKKEMLVDGQTHLVLIREEAGAPD--AKFSGW---ADAVIFVFSL 145
Cdd:cd04144   1 KLVVLGDGGVGKTALTIQLCLNHFvETYDPTIEDSYRKQVVVDGQPCMLEVLDTAGQEEytALRDQWireGEGFILVYSI 80
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 7661962  146 EDENSFQAVSRLHGQLSSLRGEGRGGLALALVGTQ-DRISAsspRVVGDARARALCADMKrCSYYETCATYGLNVDRVFQ 224
Cdd:cd04144  81 TSRSTFERVERFREQIQRVKDESAADVPIMIVGNKcDKVYE---REVSTEEGAALARRLG-CEFIEASAKTNVNVERAFY 156
                       170
                ....*....|....
gi 7661962  225 EVAQKvvtLRKQQQ 238
Cdd:cd04144 157 TLVRA---LRQQRQ 167
RSR1 cd04177
RSR1/Bud1p family GTPase; RSR1/Bud1p is a member of the Rap subfamily of the Ras family that ...
70-231 9.79e-11

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  Cd Length: 168  Bit Score: 62.11  E-value: 9.79e-11
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 7661962   70 ELRLGVLGDARSGKSSLIHRFLTGSY-QVLEKTESEQYKKEMLVDGQTHLVLIREEAGApdAKFSGWADAVI-------F 141
Cdd:cd04177   1 DYKIVVLGAGGVGKSALTVQFVQNVFiESYDPTIEDSYRKQVEIDGRQCDLEILDTAGT--EQFTAMRELYIksgqgflL 78
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 7661962  142 VFSLEDENSFQAVSRLHGQLssLRGEGRGGLALALVGTQDRISASspRVVGDARARALCADMKRCSYYETCATYGLNVDR 221
Cdd:cd04177  79 VYSVTSEASLNELGELREQV--LRIKDSDNVPMVLVGNKADLEDD--RQVSREDGVSLSQQWGNVPFYETSARKRTNVDE 154
                       170
                ....*....|
gi 7661962  222 VFQEVAQKVV 231
Cdd:cd04177 155 VFIDLVRQII 164
Ras_dva cd04147
Ras - dorsal-ventral anterior localization (Ras-dva) family; Ras-dva subfamily. Ras-dva (Ras - ...
72-230 1.27e-10

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  Cd Length: 197  Bit Score: 61.78  E-value: 1.27e-10
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 7661962   72 RLGVLGDARSGKSSLIHRFLTGSYQVLEK-TESEQYKKEMLVDGQTHLVLIREEAGAPD----AKFS-GWADAVIFVFSL 145
Cdd:cd04147   1 RLVFMGAAGVGKTALIQRFLYDTFEPKHRrTVEELHSKEYEVAGVKVTIDILDTSGSYSfpamRKLSiQNGDAFALVYSV 80
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 7661962  146 EDENSFQAVSRLHGQLSSLRGEGrgglALALVGTQDRISASSPRVVGDARARALCADMKRCSYYETCATYGLNVDRVFQE 225
Cdd:cd04147  81 DDPESFEEVKRLREEILEVKEDK----FVPIVVVGNKIDSLAERQVEAADALSTVELDWNNGFVEASAKDNENVTEVFKE 156

                ....*
gi 7661962  226 VAQKV 230
Cdd:cd04147 157 LLQQA 161
ANK cd00204
ankyrin repeats; ankyrin repeats mediate protein-protein interactions in very diverse ...
732-792 1.31e-10

ankyrin repeats; ankyrin repeats mediate protein-protein interactions in very diverse families of proteins. The number of ANK repeats in a protein can range from 2 to over 20 (ankyrins, for example). ANK repeats may occur in combinations with other types of domains. The structural repeat unit contains two antiparallel helices and a beta-hairpin, repeats are stacked in a superhelical arrangement; this alignment contains 4 consecutive repeats.


Pssm-ID: 238125  Cd Length: 126  Bit Score: 60.86  E-value: 1.31e-10
                        10        20        30        40        50        60
                ....*....|....*....|....*....|....*....|....*....|....*....|.
gi 7661962  732 DPQLRSPLHLAAELAHVVITQLLLWYGADVAARDAQGRTALFYARQAGSQLCADILLQHGC 792
Cdd:cd00204   4 DEDGRTPLHLAASNGHLEVVKLLLENGADVNAKDNDGRTPLHLAAKNGHLEIVKLLLEKGA 64
Rab9 cd04116
Rab GTPase family 9 (Rab9); Rab9 is found in late endosomes, together with mannose 6-phosphate ...
71-230 3.79e-10

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


Pssm-ID: 206697  Cd Length: 170  Bit Score: 60.27  E-value: 3.79e-10
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 7661962   71 LRLGVLGDARSGKSSLIHRFLTGSY--QVLEKTESEQYKKEMLVDGQTHLVLIREEAGAPDAK-----FSGWADAVIFVF 143
Cdd:cd04116   6 LKVILLGDGGVGKSSLMNRYVTNKFdtQLFHTIGVEFLNKDLEVDGHFVTLQIWDTAGQERFRslrtpFYRGSDCCLLTF 85
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 7661962  144 SLEDENSFQAVSRLHGQL---SSLRGEGRggLALALVGTQDRISAsspRVVGDARARALCADMKRCSYYETCATYGLNVD 220
Cdd:cd04116  86 SVDDSQSFQNLSNWKKEFiyyADVKEPES--FPFVILGNKIDIPE---RQVSTEEAQAWCRDNGDYPYFETSAKDATNVA 160
                       170
                ....*....|
gi 7661962  221 RVFQEVAQKV 230
Cdd:cd04116 161 AAFEEAVRRV 170
Ank_2 pfam12796
Ankyrin repeats (3 copies);
702-792 4.04e-10

Ankyrin repeats (3 copies);


Pssm-ID: 315466  Cd Length: 92  Bit Score: 58.97  E-value: 4.04e-10
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 7661962    702 LWAAVQAQDVATVLLLLAHarhgPLDTSVEDPQLRSPLHLAAELAHVVITQLLLWYgADVAARDAQGRTALFYARQAGSQ 781
Cdd:pfam12796   1 LHLAAKNGDLELVKLLLEE----GADANLQDKNGRTALHLAAKNGHLEIVKLLLEH-ADVNLKDKNGRTALHYAARSGHL 75
                          90
                  ....*....|.
gi 7661962    782 LCADILLQHGC 792
Cdd:pfam12796  76 EIVKLLLEKGA 86
RGK cd04148
Rem, Rem2, Rad, Gem/Kir (RGK) subfamily of Ras GTPases; RGK subfamily. The RGK (Rem, Rem2, Rad, ...
71-236 4.90e-10

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  Cd Length: 219  Bit Score: 60.11  E-value: 4.90e-10
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 7661962   71 LRLGVLGDARSGKSSLIHRFLTGSYQVLEKTES--EQYKKEMLVDGQ-THLVLIreeaGAPDAKFSGW--------ADAV 139
Cdd:cd04148   1 YRVVLLGDSGVGKSSLANIFTAGVYEDSAYEASgdDTYERTVSVDGEeATLVVY----DHWEQEDGMWledscmqvGDAY 76
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 7661962  140 IFVFSLEDENSFQAVSRLHGQLSslRGEGRGGLALALVGTQDRISASspRVVGDARARAlCADMKRCSYYETCATYGLNV 219
Cdd:cd04148  77 VIVYSVTDRSSFEKASELRIQLR--RARQAEDIPIILVGNKSDLVRS--REVSVQEGRA-CAVVFDCKFIETSAALQHNV 151
                       170
                ....*....|....*..
gi 7661962  220 DRVFqEVAQKVVTLRKQ 236
Cdd:cd04148 152 DELF-EGIVRQVRLRRD 167
Rab23_like cd04106
Rab GTPase family 23 (Rab23)-like; Rab23-like subfamily. Rab23 is a member of the Rab family ...
75-229 8.24e-10

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  Cd Length: 162  Bit Score: 58.99  E-value: 8.24e-10
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 7661962   75 VLGDARSGKSSLIHRFLTGSYqvlekteSEQYKKEMLVDGQTHLVLIREEagAPDAKFSGW------------------A 136
Cdd:cd04106   5 VVGNGNVGKSSMIQRFVKGIF-------TKDYKKTIGVDFLEKQIFLRQS--DEDVRLMLWdtagqeefdaitkayyrgA 75
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 7661962  137 DAVIFVFSLEDENSFQAVSRLHGQLSSLRGEgrgglaLALVGTQDRISASSPRVVGDARARALCADMKrCSYYETCATYG 216
Cdd:cd04106  76 QACILVFSTTDRESFEAIESWKEKVEAECGD------IPMVLVQTKIDLLDQAVITNEEAEALAKRLQ-LPLFRTSVKDD 148
                       170
                ....*....|...
gi 7661962  217 LNVDRVFQEVAQK 229
Cdd:cd04106 149 FNVTELFEYLAEK 161
Rhes_like cd04143
Ras homolog enriched in striatum (Rhes) and activator of G-protein signaling 1 (Dexras1/AGS1); ...
72-227 1.00e-09

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  Cd Length: 247  Bit Score: 59.76  E-value: 1.00e-09
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 7661962   72 RLGVLGDARSGKSSLIHRFLTGSYQ-VLEKTESEQYKKEMLVDGQTHLVLIREEAGAPD--AK-----FSGwaDAVIFVF 143
Cdd:cd04143   2 RMVVLGASKVGKTAIVSRFLGGRFEeQYTPTIEDFHRKLYSIRGEVYQLDILDTSGNHPfpAMrrlsiLTG--DVFILVF 79
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 7661962  144 SLEDENSFQAVSRLHGQL----SSLRGEGRGGLALALVGTQDRISASSPRVVGDARARALCADMKRCSYYETCATYGLNV 219
Cdd:cd04143  80 SLDNRESFEEVCRLREQIletkSCLKNKTKENVKIPMVICGNKADRDFPREVQRDEVEQLVGGDENCAYFEVSAKKNSNL 159

                ....*...
gi 7661962  220 DRVFQEVA 227
Cdd:cd04143 160 DEMFRALF 167
Rap1 cd04175
Rap1 family GTPase consists of Rap1a and Rap1b isoforms; The Rap1 subgroup is part of the Rap ...
70-230 2.24e-09

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


Pssm-ID: 133375  Cd Length: 164  Bit Score: 57.53  E-value: 2.24e-09
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 7661962   70 ELRLGVLGDARSGKSSLIHRFLTGSYqvLEK---TESEQYKKEMLVDGQTHLVLIREEAGApdAKFSGWAD-------AV 139
Cdd:cd04175   1 EYKLVVLGSGGVGKSALTVQFVQGIF--VEKydpTIEDSYRKQVEVDGQQCMLEILDTAGT--EQFTAMRDlymkngqGF 76
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 7661962  140 IFVFSLEDENSFQAVSRLHGQLssLRGEGRGGLALALVGtqDRISASSPRVVGDARARALcADMKRCSYYETCATYGLNV 219
Cdd:cd04175  77 VLVYSITAQSTFNDLQDLREQI--LRVKDTEDVPMILVG--NKCDLEDERVVGKEQGQNL-ARQWGCAFLETSAKAKINV 151
                       170
                ....*....|.
gi 7661962  220 DRVFQEVAQKV 230
Cdd:cd04175 152 NEIFYDLVRQI 162
Rab21 cd04123
Rab GTPase family 21 (Rab21); The localization and function of Rab21 are not clearly defined, ...
76-231 4.42e-09

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


Pssm-ID: 133323  Cd Length: 162  Bit Score: 56.85  E-value: 4.42e-09
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 7661962   76 LGDARSGKSSLIHRFLTGSYQvlEKTESE-----QYKKEMLVDGQTHLVlIREEAG-------AP----DAkfsgwaDAV 139
Cdd:cd04123   6 LGEGRVGKTSLVLRYVENKFN--EKHESTtqasfFQKTVNIGGKRIDLA-IWDTAGqeryhalGPiyyrDA------DGA 76
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 7661962  140 IFVFSLEDENSFQAVSRLHGQLSSLRGEgrgGLALALVGtqDRISASSPRVVGDARARALCADMKrCSYYETCATYGLNV 219
Cdd:cd04123  77 ILVYDITDADSFQKVKKWIKELKQMRGN---NISLVIVG--NKIDLERQRVVSKSEAEEYAKSVG-AKHFETSAKTGKGI 150
                       170
                ....*....|..
gi 7661962  220 DRVFQEVAQKVV 231
Cdd:cd04123 151 EELFLSLAKRMI 162
Rab5_related cd01860
Rab-related GTPase family includes Rab5 and Rab22; regulates early endosome fusion; The ...
70-230 1.39e-08

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  Cd Length: 163  Bit Score: 55.25  E-value: 1.39e-08
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 7661962   70 ELRLGVLGDARSGKSSLIHRFLTGSYqvLEKTESEQ----YKKEMLVDGQTHLVLIREEAG-------APdAKFSGwADA 138
Cdd:cd01860   1 QFKLVLLGDSSVGKSSIVLRFVKNEF--SENQESTIgaafLTQTVNLDDTTVKFEIWDTAGqeryrslAP-MYYRG-AAA 76
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 7661962  139 VIFVFSLEDENSFQavsRLHGQLSSLRGEGRGGLALALVGtqDRISASSPRVVGDARARALcADMKRCSYYETCATYGLN 218
Cdd:cd01860  77 AIVVYDITSEESFE---KAKSWVKELQEHGPPNIVIALAG--NKADLESKRQVSTEEAQEY-ADENGLLFMETSAKTGEN 150
                       170
                ....*....|..
gi 7661962  219 VDRVFQEVAQKV 230
Cdd:cd01860 151 VNELFTEIARKL 162
RalA_RalB cd04139
Ral (Ras-like) family containing highly homologous RalA and RalB; The Ral (Ras-like) subfamily ...
75-230 2.26e-07

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


Pssm-ID: 206710  Cd Length: 163  Bit Score: 51.27  E-value: 2.26e-07
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 7661962   75 VLGDARSGKSSLIHRFLTGSYQV-LEKTESEQYKKEMLVDGQTHLVLIREEAGAPDAK-----FSGWADAVIFVFSLEDE 148
Cdd:cd04139   5 MVGSGGVGKSALTLQFMYDEFVEdYEPTKADSYRKKVVLDGEEVQLNILDTAGQEDYAairdnYFRSGEGFLLVFSITDM 84
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 7661962  149 NSFQAVSRLHGQLssLRGEGRGGLALALVGtqDRISASSPRVVGDARARALCADMKrCSYYETCATYGLNVDRVFQEVAQ 228
Cdd:cd04139  85 ESFTALAEFREQI--LRVKEDDNVPLLLVG--NKCDLEDKRQVSVEEAANLAEQWG-VNYVETSAKTRANVDKVFFDLVR 159

                ..
gi 7661962  229 KV 230
Cdd:cd04139 160 EI 161
H_N_K_Ras_like cd04138
Ras GTPase family containing H-Ras,N-Ras and K-Ras4A/4B; H-Ras/N-Ras/K-Ras subfamily. H-Ras, ...
70-223 1.07e-06

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  Cd Length: 162  Bit Score: 49.34  E-value: 1.07e-06
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 7661962   70 ELRLGVLGDARSGKSSLIHRfLTGSYQVLE--KTESEQYKKEMLVDGQTHLVLI-----REEAGAPDAKFSGWADAVIFV 142
Cdd:cd04138   1 EYKLVVVGAGGVGKSALTIQ-LIQNHFVDEydPTIEDSYRKQVVIDGETCLLDIldtagQEEYSAMRDQYMRTGEGFLCV 79
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 7661962  143 FSLEDENSFQAVSRLHGQLssLRGEGRGGLALALVGTQDRISAsspRVVGDARARALCADMKrCSYYETCATYGLNVDRV 222
Cdd:cd04138  80 FAINSRKSFEDIHTYREQI--KRVKDSDDVPMVLVGNKCDLAA---RTVSSRQGQDLAKSYG-IPYIETSAKTRQGVEEA 153

                .
gi 7661962  223 F 223
Cdd:cd04138 154 F 154
RheB cd04137
Ras Homolog Enriched in Brain (RheB) is a small GTPase; Rheb (Ras Homolog Enriched in Brain) ...
75-230 1.13e-06

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  Cd Length: 180  Bit Score: 49.55  E-value: 1.13e-06
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 7661962   75 VLGdARS-GKSSLIHRFLTG----SYqvlEKTESEQYKKEMLVDGQTHLVLIREEAGAPD-----AKFSGWADAVIFVFS 144
Cdd:cd04137   6 VLG-SRSvGKSSLTVQFVEGhfveSY---YPTIENTFSKIITYKGQEYHLEIVDTAGQDEysilpQKYSIGIHGYILVYS 81
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 7661962  145 LEDENSFQAVSRLHGQLssLRGEGRGGLALALVGTqdRISASSPRVVGDARARALcADMKRCSYYETCATYGLNVDRVFQ 224
Cdd:cd04137  82 VTSRKSFEVVKVIYDKI--LDMLGKESVPIVLVGN--KSDLHMERQVSAEEGKKL-AESWGAAFLESSAKENENVEEAFE 156

                ....*.
gi 7661962  225 EVAQKV 230
Cdd:cd04137 157 LLIEEI 162
PLN03118 PLN03118
Rab family protein; Provisional
75-231 2.24e-06

Rab family protein; Provisional


Pssm-ID: 215587  Cd Length: 211  Bit Score: 49.28  E-value: 2.24e-06
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 7661962    75 VLGDARSGKSSLIHRFLTGSYQVLEKTESEQYK-KEMLVDGQTHLVLIREEAGAP-----DAKFSGWADAVIFVFSLEDE 148
Cdd:PLN03118  19 LIGDSGVGKSSLLVSFISSSVEDLAPTIGVDFKiKQLTVGGKRLKLTIWDTAGQErfrtlTSSYYRNAQGIILVYDVTRR 98
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 7661962   149 NSFQAVSRLHGQLSSLRGEGRGGLALaLVGtqDRISASSPRVVGDARARALcADMKRCSYYETCATYGLNVDRVFQEVAQ 228
Cdd:PLN03118  99 ETFTNLSDVWGKEVELYSTNQDCVKM-LVG--NKVDRESERDVSREEGMAL-AKEHGCLFLECSAKTRENVEQCFEELAL 174

                 ...
gi 7661962   229 KVV 231
Cdd:PLN03118 175 KIM 177
RJL cd04119
Rab GTPase family J-like (RabJ-like); RJLs are found in many protists and as chimeras with ...
75-224 2.61e-06

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  Cd Length: 168  Bit Score: 48.12  E-value: 2.61e-06
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 7661962   75 VLGDARSGKSSLIHRFLTG------------SYQVlekteseqykKEMLVDGQTHLVLIREEAGAPD-----AKFSGWAD 137
Cdd:cd04119   5 SMGNSGVGKSCIIKRYCEGrfvskylptigiDYGV----------KKVSVRNKEVRVNFFDLSGHPEylevrNEFYKDTQ 74
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 7661962  138 AVIFVFSLEDENSFQAVSRLHGQLSSLRGEGRGGLALALVGTQDRISASSPRVVGDARARALcADMKRCSYYETCATYGL 217
Cdd:cd04119  75 GVLLVYDVTDRQSFEALDSWLKEMKQEGGPHGNMENIVVVVCANKIDLTKHRAVSEDEGRLW-AESKGFKYFETSACTGE 153

                ....*..
gi 7661962  218 NVDRVFQ 224
Cdd:cd04119 154 GVNEMFQ 160
RRP22 cd04142
Ras-related protein on chromosome 22 (RRP22) family; RRP22 (Ras-related protein on chromosome ...
71-235 2.63e-06

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


Pssm-ID: 133342  Cd Length: 198  Bit Score: 48.71  E-value: 2.63e-06
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 7661962   71 LRLGVLGDARSGKSSLIHRFLTGSY--QVLEKTESEQYKKEMLVDGQTHLVLIREEAGA-----------PDAKFSGW-- 135
Cdd:cd04142   1 VRVAVLGAPGVGKTAIVRQFLAQEFpeEYIPTEHRRLYRPAVVLSGRVYDLHILDVPNMqrypgtagqewMDPRFRGLrn 80
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 7661962  136 ADAVIFVFSLEDENSFQAVSRLHGQLSSLRGEGRGGLALALVGT---QDRISASSPRVVGdararALCADMKRCSYYETC 212
Cdd:cd04142  81 SRAFILVYDICSPDSFHYVKLLRQQILETRPAGNKEPPIVVVGNkrdQQRHRFAPRHVLS-----VLVRKSWKCGYLECS 155
                       170       180
                ....*....|....*....|...
gi 7661962  213 ATYGLNVDRVFQEVAQKVVTLRK 235
Cdd:cd04142 156 AKYNWHILLLFKELLISATTRGR 178
Wrch_1 cd04130
Wnt-1 responsive Cdc42 homolog (Wrch-1) is a Rho family GTPase similar to Cdc42; Wrch-1 (Wnt-1 ...
76-223 6.02e-06

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


Pssm-ID: 133330  Cd Length: 173  Bit Score: 47.01  E-value: 6.02e-06
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 7661962   76 LGDARSGKSSLIHRFLTGSYQV-LEKTESEQYKKEMLVDGQ-THLVLIrEEAGAPDakFSGW-------ADAVIFVFSLE 146
Cdd:cd04130   6 VGDGAVGKTSLIVSYTTNGYPTeYVPTAFDNFSVVVLVDGKpVRLQLC-DTAGQDE--FDKLrplcypdTDVFLLCFSVV 82
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 7661962  147 DENSFQAVSrlHGQLSSLRgEGRGGLALALVGTQD----------RISASSPRVVGDARARALCADMKRCSYYETCATYG 216
Cdd:cd04130  83 NPSSFQNIS--EKWIPEIR-KHNPKAPIILVGTQAdlrtdvnvliQLARYGEKPVSQSRAKALAEKIGACEYIECSALTQ 159

                ....*..
gi 7661962  217 LNVDRVF 223
Cdd:cd04130 160 KNLKEVF 166
PLN03131 PLN03131
hypothetical protein; Provisional
568-682 1.21e-05

hypothetical protein; Provisional


Pssm-ID: 178677  Cd Length: 705  Bit Score: 48.62  E-value: 1.21e-05
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 7661962   568 RTDSQSEAVAIQAIRNAKGNSICVDCGAPNPTWASLNLGALICIECSGIHRNLgTHlsRVRSLDLDDWPRELTLVLTAIG 647
Cdd:PLN03131   4 RKEEERNEKIIRGLMKLPPNRRCINCNSLGPQFVCTNFWTFICMTCSGIHREF-TH--RVKSVSMSKFTSQDVEALQNGG 80
                         90       100       110
                 ....*....|....*....|....*....|....*.
gi 7661962   648 NDTANRVWESD-TRGRAKPSRDSSREERESWIRAKY 682
Cdd:PLN03131  81 NQRAREIYLKDwDQQRQRLPDNSKVDKIREFIKDIY 116
PH1_Pleckstrin_2 cd13301
Pleckstrin 2 Pleckstrin homology (PH) domain, repeat 1; Pleckstrin is a protein found in ...
520-566 1.57e-05

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


Pssm-ID: 270113  Cd Length: 108  Bit Score: 45.44  E-value: 1.57e-05
                        10        20        30        40
                ....*....|....*....|....*....|....*....|....*..
gi 7661962  520 FEFLIVSSTGQTWHFEAASFEERDAWVQAIESQIlaslQCCESSKVK 566
Cdd:cd13301  65 LVFKLTTAKGQEHFFQACSREERDAWAKDITKAI----TCLEGGKRF 107
Rab6 cd01861
Rab GTPase family 6 (Rab6); Rab6 is involved in microtubule-dependent transport pathways ...
76-229 1.93e-05

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  Cd Length: 161  Bit Score: 45.31  E-value: 1.93e-05
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 7661962   76 LGDARSGKSSLIHRFLTGSYqvlekteSEQYK---------KEMLVDGQTHLVLIREEAGapDAKFSGW-------ADAV 139
Cdd:cd01861   6 LGDQSVGKTSIITRFMYDTF-------DNQYQatigidflsKTMYVDDKTVRLQLWDTAG--QERFRSLipsyirdSSVA 76
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 7661962  140 IFVFSLEDENSFQAVSRLhgqLSSLRGEgRGGLAL-ALVGtqDRISASSPRVVGDARARALcADMKRCSYYETCATYGLN 218
Cdd:cd01861  77 VVVYDITNRQSFDNTDKW---IDDVRDE-RGNDVIiVLVG--NKTDLSDKRQVSTEEGEKK-AKENNAMFIETSAKAGHN 149
                       170
                ....*....|.
gi 7661962  219 VDRVFQEVAQK 229
Cdd:cd01861 150 VKQLFKKIAQA 160
Rab28 cd04109
Rab GTPase family 28 (Rab28); Rab28 subfamily. First identified in maize, Rab28 has been shown ...
71-238 2.12e-05

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


Pssm-ID: 206694  Cd Length: 213  Bit Score: 46.33  E-value: 2.12e-05
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 7661962   71 LRLGVLGDARSGKSSLIHRFLTGSYqvlekteSEQYKKEMLVDGQTHLVLIREE---------------AGAPDAKFSGW 135
Cdd:cd04109   1 IKIVVLGDGASGKTSLIRRFAQEGF-------GKSYKQTIGLDFFSRRITLPGSlnvtlqvwdiggqqiGGKMLDKYIYG 73
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 7661962  136 ADAVIFVFSLEDENSFQAVSRLHGQLSSLRGEGRGGLALALVGtqDRISASSPRVVGDARARALCADMKRCSYYETCATy 215
Cdd:cd04109  74 AQAVCLVYDITNSQSFENLEDWLSVVKKVNEESETKPKMVLVG--NKTDLEHNRQVTAEKHARFAQENDMESIFVSAKT- 150
                       170       180
                ....*....|....*....|...
gi 7661962  216 GLNVDRVFQEVAQKVVTLRKQQQ 238
Cdd:cd04109 151 GDRVFLCFQRIAAELLGVKLSQA 173
Ank_5 pfam13857
Ankyrin repeats (many copies);
721-775 2.15e-05

Ankyrin repeats (many copies);


Pssm-ID: 316380  Cd Length: 56  Bit Score: 44.28  E-value: 2.15e-05
                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....*
gi 7661962    721 ARHGPLDTSVEDPQLRSPLHLAAELAHVVITQLLLWYGADVAARDAQGRTALFYA 775
Cdd:pfam13857   2 LENGPADLNRLDGEGYTPLHLAAKYGALEIVRLLLKRGADLNLKDFRGLTALDLA 56
Rab18 cd01863
Rab GTPase family 18 (Rab18); Rab18 subfamily. Mammalian Rab18 is implicated in endocytic ...
71-230 2.26e-05

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


Pssm-ID: 206656  Cd Length: 161  Bit Score: 45.38  E-value: 2.26e-05
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 7661962   71 LRLGVLGDARSGKSSLIHRFLTGSY-QVLEKTESEQYK-KEMLVDGQTHLVLIREEAGAP-----DAKFSGWADAVIFVF 143
Cdd:cd01863   1 LKILLIGDSGVGKSSLLLRFTDDTFdEDLSSTIGVDFKvKTVTVDGKKVKLAIWDTAGQErfrtlTSSYYRGAQGVILVY 80
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 7661962  144 SLEDENSFQAVSRLHGQLSSLrgEGRGGLALALVGTQ-DRISASSPRVVGDARARalcadMKRCSYYETCATYGLNVDRV 222
Cdd:cd01863  81 DVTRRDTFDNLDTWLNELDTY--STNPDAVKMLVGNKiDKENREVTREEGQKFAR-----KHNMLFIETSAKTRIGVQQA 153

                ....*...
gi 7661962  223 FQEVAQKV 230
Cdd:cd01863 154 FEELVEKI 161
PTZ00322 PTZ00322
6-phosphofructo-2-kinase/fructose-2,6-biphosphatase; Provisional
724-797 2.28e-05

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


Pssm-ID: 140343  Cd Length: 664  Bit Score: 47.97  E-value: 2.28e-05
                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 7661962   724 GPLDTSVEDPQLRSPLHLAAELAHVVITQLLLWYGADVAARDAQGRTALFYARQAGSQLCADILLQHG-CPGEGG 797
Cdd:PTZ00322 104 GGADPNCRDYDGRTPLHIACANGHVQVVRVLLEFGADPTLLDKDGKTPLELAEENGFREVVQLLSRHSqCHFELG 178
PTZ00369 PTZ00369
Ras-like protein; Provisional
70-230 3.28e-05

Ras-like protein; Provisional


Pssm-ID: 240385  Cd Length: 189  Bit Score: 45.24  E-value: 3.28e-05
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 7661962    70 ELRLGVLGDARSGKSSLIHRFLTGSY-QVLEKTESEQYKKEMLVDGQTHLVLIREEAGAPDakFSGWAD-------AVIF 141
Cdd:PTZ00369   5 EYKLVVVGGGGVGKSALTIQFIQNHFiDEYDPTIEDSYRKQCVIDEETCLLDILDTAGQEE--YSAMRDqymrtgqGFLC 82
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 7661962   142 VFSLEDENSFQAVSRLHGQLssLRGEGRGGLALALVGtqDRISASSPRVVGDARARALCADMKrCSYYETCATYGLNVDR 221
Cdd:PTZ00369  83 VYSITSRSSFEEIASFREQI--LRVKDKDRVPMILVG--NKCDLDSERQVSTGEGQELAKSFG-IPFLETSAKQRVNVDE 157

                 ....*....
gi 7661962   222 VFQEVAQKV 230
Cdd:PTZ00369 158 AFYELVREI 166
PLN03119 PLN03119
putative ADP-ribosylation factor GTPase-activating protein AGD14; Provisional
568-684 4.22e-05

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


Pssm-ID: 178666  Cd Length: 648  Bit Score: 46.76  E-value: 4.22e-05
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 7661962   568 RTDSQSEAVaIQAIRNAKGNSICVDCGAPNPTWASLNLGALICIECSGIHRNLgTHlsRVRSLDLDDWPRELTLVLTAIG 647
Cdd:PLN03119   5 REEERNEKI-IRGLMKLPPNRRCINCNSLGPQYVCTTFWTFVCMACSGIHREF-TH--RVKSVSMSKFTSKEVEVLQNGG 80
                         90       100       110
                 ....*....|....*....|....*....|....*...
gi 7661962   648 NDTANRVWESD-TRGRAKPSRDSSREERESWIRAKYEQ 684
Cdd:PLN03119  81 NQRAREIYLKNwDHQRQRLPENSNAERVREFIKNVYVQ 118
Gem1 COG1100
GTPase SAR1 family domain [General function prediction only];
69-239 4.35e-05

GTPase SAR1 family domain [General function prediction only];


Pssm-ID: 224025  Cd Length: 219  Bit Score: 45.34  E-value: 4.35e-05
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 7661962   69 PELRLGVLGDARSGKSSLIHRFLTGSY-QVLEKTESEQY-KKEMLVDGQTHLVLIREEAGAPDAK------FSGwADAVI 140
Cdd:COG1100   4 KEFKIVVLGDGGVGKTTLLNRLVGDEFpEGYPPTIGNLDpAKTIEPYRRNIKLQLWDTAGQEEYRslrpeyYRG-ANGIL 82
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 7661962  141 FVFSLED-ENSFQAVSRLHGQLSSLRGEgrgGLALALVGTQ----DRISASSPRVVGDARARALCADMKRC--------S 207
Cdd:COG1100  83 IVYDSTLrESSDELTEEWLEELRELAPD---DVPILLVGNKidlfDEQSSSEEILNQLNREVVLLVLAPKAvlpevanpA 159
                       170       180       190
                ....*....|....*....|....*....|....
gi 7661962  208 YYETCATY--GLNVDRVFQEVAQKVVTLRKQQQL 239
Cdd:COG1100 160 LLETSAKSltGPNVNELFKELLRKLLEEIEKLVL 193
PH smart00233
Pleckstrin homology domain; Domain commonly found in eukaryotic signalling proteins. The ...
508-553 5.22e-05

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


Pssm-ID: 214574  Cd Length: 102  Bit Score: 43.69  E-value: 5.22e-05
                           10        20        30        40
                   ....*....|....*....|....*....|....*....|....*.
gi 7661962     508 TEGSAGQAEEENFEFLIVSSTGQTWHFEAASFEERDAWVQAIESQI 553
Cdd:smart00233  56 REAPDPDSSKKPHCFEIKTSDRKTLLLQAESEEEREKWVEALRKAI 101
Ank pfam00023
Ankyrin repeat; Ankyrins are multifunctional adaptors that link specific proteins to the ...
736-765 7.41e-05

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


Pssm-ID: 306522  Cd Length: 33  Bit Score: 42.24  E-value: 7.41e-05
                          10        20        30
                  ....*....|....*....|....*....|
gi 7661962    736 RSPLHLAAELAHVVITQLLLWYGADVAARD 765
Cdd:pfam00023   3 NTPLHLAAREGNLEIVKLLLSKGADVNARD 32
PH cd00821
Pleckstrin homology (PH) domain; PH domains have diverse functions, but in general are ...
491-549 7.65e-05

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  Cd Length: 92  Bit Score: 42.91  E-value: 7.65e-05
                        10        20        30        40        50
                ....*....|....*....|....*....|....*....|....*....|....*....
gi 7661962  491 SPMVKKQRRKKLTTPSKTEGSAGQAEEENFEFLIVSSTGQTWHFEAASFEERDAWVQAI 549
Cdd:cd00821  34 KKDSSYKPKGSIPLSGILEVEEVSPKERPHCFELVTPDGRTYYLQADSEEERQEWLKAL 92
Rab24 cd04118
Rab GTPase family 24 (Rab24); Rab24 is distinct from other Rabs in several ways. It exists ...
71-237 9.80e-05

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  Cd Length: 193  Bit Score: 44.09  E-value: 9.80e-05
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 7661962   71 LRLGVLGDARSGKSSLI-----HRFLTGSYQvleKTESEQYKKEMLVDGQTHLVL-IREEAG-----APDAKFSGWADAV 139
Cdd:cd04118   1 VKVVMLGKESVGKTSLVeryvhHRFLVGPYQ---NTIGAAFVAKRMVVGERVVTLgIWDTAGseryeAMSRIYYRGAKAA 77
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 7661962  140 IFVFSLEDENSFQAVSRLHGQLSSLRGEGRgglaLALVGTQ-DRISASSPRVVGDARARALCADMKRCSYYETCATYGLN 218
Cdd:cd04118  78 IVCYDLTDSSSFERAKFWVKELQNLEEHCK----IYLCGTKsDLIEQDRSLRQVDFHDVQDFADEIKAQHFETSSKTGQN 153
                       170
                ....*....|....*....
gi 7661962  219 VDRVFQEVAQKVVTLRKQQ 237
Cdd:cd04118 154 VDELFQKVAEDFVSRANNQ 172
PH smart00233
Pleckstrin homology domain; Domain commonly found in eukaryotic signalling proteins. The ...
341-405 1.54e-04

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  Cd Length: 102  Bit Score: 42.15  E-value: 1.54e-04
                           10        20        30        40        50        60
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 7661962     341 PIKQSFLLKRSGNSlNKEWKKKYVTLsSNGFLLYHPSINDYIHSTHGKEMDLLRTTVKVPGKRPP 405
Cdd:smart00233   1 VIKEGWLYKKSGGG-KKSWKKRYFVL-FNSTLLYYKSKKDKKSYKPKGSIDLSGCTVREAPDPDS 63
Ank_4 pfam13637
Ankyrin repeats (many copies);
736-775 1.59e-04

Ankyrin repeats (many copies);


Pssm-ID: 316185  Cd Length: 54  Bit Score: 41.50  E-value: 1.59e-04
                          10        20        30        40
                  ....*....|....*....|....*....|....*....|
gi 7661962    736 RSPLHLAAELAHVVITQLLLWYGADVAARDAQGRTALFYA 775
Cdd:pfam13637   2 LTALHAAAASGHLELLRLLLENGADINAVDGNGETALHFA 41
Ank_2 pfam12796
Ankyrin repeats (3 copies);
702-765 1.90e-04

Ankyrin repeats (3 copies);


Pssm-ID: 315466  Cd Length: 92  Bit Score: 41.63  E-value: 1.90e-04
                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....
gi 7661962    702 LWAAVQAQDVATVLLLLAHArhgplDTSVEDPQLRSPLHLAAELAHVVITQLLLWYGADVAARD 765
Cdd:pfam12796  34 LHLAAKNGHLEIVKLLLEHA-----DVNLKDKNGRTALHYAARSGHLEIVKLLLEKGADINVKD 92
PLN03192 PLN03192
Voltage-dependent potassium channel; Provisional
726-789 2.67e-04

Voltage-dependent potassium channel; Provisional


Pssm-ID: 215625  Cd Length: 823  Bit Score: 44.47  E-value: 2.67e-04
                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|....
gi 7661962   726 LDTSVEDPQLRSPLHLAAELAHVVITQLLLWYGADVAARDAQGRTALFYARQAGSQLCADILLQ 789
Cdd:PLN03192 549 LDPDIGDSKGRTPLHIAASKGYEDCVLVLLKHACNVHIRDANGNTALWNAISAKHHKIFRILYH 612
ANKYR COG0666
Ankyrin repeat [Signal transduction mechanisms];
703-791 3.09e-04

Ankyrin repeat [Signal transduction mechanisms];


Pssm-ID: 223738  Cd Length: 235  Bit Score: 43.27  E-value: 3.09e-04
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 7661962  703 WAAVQAQDVA----TVLLLLAHARHGPLDTsVEDPQLRSPLHLAAELAHVVITQLLLWYGADVAARDAQGRTALFYARQA 778
Cdd:COG0666 112 LAALNGNPPEgnieVAKLLLEAGADLDVNN-LRDEDGNTPLHWAALNGDADIVELLLEAGADPNSRNSYGVTALDPAAKN 190
                        90
                ....*....|...
gi 7661962  779 GSQLCADILLQHG 791
Cdd:COG0666 191 GRIELVKLLLDKG 203
RabL2 cd04124
Rab GTPase-like family 2 (Rab-like2); RabL2 (Rab-like2) subfamily. RabL2s are novel Rab ...
71-231 5.05e-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  Cd Length: 161  Bit Score: 41.38  E-value: 5.05e-04
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 7661962   71 LRLGVLGDARSGKSSLIHRFLTGSY--QVLEKTESEQYKKEMLVDGQTHLVLIREEAGAP-----DAKFSGWADAVIFVF 143
Cdd:cd04124   1 VKIILLGDSAVGKSKLVERFLMDGYepQQLSTYALTLYKHNAKFEGKTILVDFWDTAGQErfqtmHASYYHKAHACILVF 80
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 7661962  144 SLEDENSFQAVSRLHGQLSSLRGEgrgglaLALVGTQDRISAsSPRVVGDARAralCADMKRCSYYETCATYGLNVDRVF 223
Cdd:cd04124  81 DVTRKITYKNLSKWYEELREYRPE------IPCIVVANKIDL-DPSVTQKKFN---FAEKHNLPLYYVSAADGTNVVKLF 150

                ....*...
gi 7661962  224 QEVAQKVV 231
Cdd:cd04124 151 QDAIKLAV 158
Roc pfam08477
Ras of Complex, Roc, domain of DAPkinase; Roc, or Ras of Complex, proteins are mitochondrial ...
72-167 5.72e-04

Ras of Complex, Roc, domain of DAPkinase; Roc, or Ras of Complex, proteins are mitochondrial Rho proteins (Miro-1, and Miro-2) and atypical Rho GTPases. Full-length proteins have a unique domain organisation, 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: 312094  Cd Length: 114  Bit Score: 40.57  E-value: 5.72e-04
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 7661962     72 RLGVLGDARSGKSSLIHRFLTGSYqvlekteSEQYKKEMLVDGQTHLVLIREEAGApDAKFSGW---------------- 135
Cdd:pfam08477   1 KIVLLGDSGVGKTSLLKRFVDDTF-------DPKYQSTIGVDFKTKTVLENDDNGK-KVKLNIWdtagqerfrslhpfyy 72
                          90       100       110
                  ....*....|....*....|....*....|....
gi 7661962    136 --ADAVIFVFsleDENSFQAVSRLHGQLSSLRGE 167
Cdd:pfam08477  73 rgAAAALLVY---DSRTFSNLKYWLRELREYAGN 103
Rit_Rin_Ric cd04141
Ras-like protein in all tissues (Rit), Ras-like protein in neurons (Rin) and Ras-related ...
70-230 9.22e-04

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  Cd Length: 172  Bit Score: 40.61  E-value: 9.22e-04
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 7661962   70 ELRLGVLGDARSGKSSLIHRFLTGSY-QVLEKTESEQYKKEMLVDGQTHLVLIREEAGapDAKFSGWAD-------AVIF 141
Cdd:cd04141   2 EYKIVMLGAGGVGKSAVTMQFISHSFpDYHDPTIEDAYKTQARIDNEPALLDILDTAG--QAEFTAMRDqymrcgeGFII 79
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 7661962  142 VFSLEDENSFQAVSRLHGQLSSLRGEGRggLALALVGtqDRISASSPRVVGDARARALcADMKRCSYYETCATYGLNVDR 221
Cdd:cd04141  80 CYSVTDRHSFQEASEFKELITRVRLTED--IPLVLVG--NKVDLEQQRQVTTEEGRNL-AREFNCPFFETSAALRFYIDD 154

                ....*....
gi 7661962  222 VFQEVAQKV 230
Cdd:cd04141 155 AFHGLVREI 163
Rab1_Ypt1 cd01869
Rab GTPase family 1 includes the yeast homolog Ypt1; Rab1/Ypt1 subfamily. Rab1 is found in ...
71-231 1.18e-03

Rab GTPase family 1 includes the yeast homolog Ypt1; Rab1/Ypt1 subfamily. Rab1 is found in every eukaryote and is a key regulatory component for the transport of vesicles from the ER to the Golgi apparatus. Studies on mutations of Ypt1, the yeast homolog of Rab1, showed that this protein is necessary for the budding of vesicles of the ER as well as for their transport to, and fusion with, the Golgi apparatus. 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: 206661  Cd Length: 166  Bit Score: 40.39  E-value: 1.18e-03
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 7661962   71 LRLGVLGDARSGKSSLIHRFLTGSYqvlekTESE------QYK-KEMLVDGQTHLVLIREEAGA------PDAKFSGwAD 137
Cdd:cd01869   3 FKLLLIGDSGVGKSCLLLRFADDTY-----TESYistigvDFKiRTIELDGKTVKLQIWDTAGQerfrtiTSSYYRG-AH 76
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 7661962  138 AVIFVFSLEDENSFQAVSRLHGQLSSLRGEGRGGLalaLVGtqDRISASSPRVVGDARARALcADMKRCSYYETCATYGL 217
Cdd:cd01869  77 GIIIVYDVTDQESFNNVKQWLQEIDRYASENVNKL---LVG--NKCDLTDKKVVDYTEAKEF-ADELGIPFLETSAKNAT 150
                       170
                ....*....|....
gi 7661962  218 NVDRVFQEVAQKVV 231
Cdd:cd01869 151 NVEEAFMTMAREIK 164
PLN03110 PLN03110
Rab GTPase; Provisional
75-241 1.60e-03

Rab GTPase; Provisional


Pssm-ID: 178657  Cd Length: 216  Bit Score: 40.68  E-value: 1.60e-03
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 7661962    75 VLGDARSGKSSLIHRFLTGSYQVLEKTE--SEQYKKEMLVDGQTHLVLIREEAGA------PDAKFSGwADAVIFVFSLE 146
Cdd:PLN03110  17 LIGDSGVGKSNILSRFTRNEFCLESKSTigVEFATRTLQVEGKTVKAQIWDTAGQeryraiTSAYYRG-AVGALLVYDIT 95
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 7661962   147 DENSFQAVSRLhgqLSSLRGEGRGGLALALVGTQDRISasSPRVVGDARARALcADMKRCSYYETCATYGLNVDRVFQEV 226
Cdd:PLN03110  96 KRQTFDNVQRW---LRELRDHADSNIVIMMAGNKSDLN--HLRSVAEEDGQAL-AEKEGLSFLETSALEATNVEKAFQTI 169
                        170
                 ....*....|....*
gi 7661962   227 AQKVVTLRKQQQLLA 241
Cdd:PLN03110 170 LLEIYHIISKKALAA 184
PH_ORP9 cd13290
Human Oxysterol binding protein related protein 9 Pleckstrin homology (PH) domain; Human ORP9 ...
493-558 2.92e-03

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


Pssm-ID: 241444  Cd Length: 102  Bit Score: 38.19  E-value: 2.92e-03
                        10        20        30        40        50        60
                ....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 7661962  493 MVKKQRRKKLTTpskTEGSAGQAEEENFEFLIvSSTGQTWHFEAASFEERDAWVQAIESQILASLQ 558
Cdd:cd13290  38 MMRGSRRGCVRL---KGAVIGIDDEDDSTFTI-TVDQKTFHFQARDAEERERWIRALEDTILRHSQ 99
Rho3 cd04134
Ras homology family 3 (Rho3) of small guanosine triphosphatases (GTPases); Rho3 is a member of ...
75-243 3.98e-03

Ras homology family 3 (Rho3) of small guanosine triphosphatases (GTPases); Rho3 is a member of the Rho family found only in fungi. Rho3 is believed to regulate cell polarity by interacting with the diaphanous/formin family protein For3 to control both the actin cytoskeleton and microtubules. Rho3 is also believed to have a direct role in exocytosis that is independent of its role in regulating actin polarity. The function in exocytosis may be two-pronged: first, in the transport of post-Golgi vesicles from the mother cell to the bud, mediated by myosin (Myo2); second, in the docking and fusion of vesicles to the plasma membrane, mediated by an exocyst (Exo70) protein. 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.


Pssm-ID: 206706  Cd Length: 185  Bit Score: 39.07  E-value: 3.98e-03
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 7661962   75 VLGDARSGKSSLIHRFLTGSY-QVLEKTESEQYKKEMLVDGQTHLVLIREEAGAPD---AKFSGWADA--VIFVFSLEDE 148
Cdd:cd04134   5 VLGDGACGKTSLLNVFTRGYFpQVYEPTVFENYIHDIFVDGLAVELSLWDTAGQEEfdrLRSLSYADThvIMLCFSVDNP 84
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 7661962  149 NSFQAV-SRLHGQLSslrgEGRGGLALALVGTQ-DRISASSPRVVGDA-----RARALCADMKRCSYYETCATYGLNVDR 221
Cdd:cd04134  85 DSLENVeSKWLAEIR----HHCPGVKLVLVALKcDLREPRNERDRGTHtisyeEGLAVAKRINACRYLECSAKLNRGVNE 160
                       170       180
                ....*....|....*....|..
gi 7661962  222 VFQEVAQKVVTLRKQQQLLAAC 243
Cdd:cd04134 161 AFTEAARVALNARPPHPHSRAC 182
PH_OSBP_ORP4 cd13284
Human Oxysterol binding protein and OSBP-related protein 4 Pleckstrin homology (PH) domain; ...
517-550 9.44e-03

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


Pssm-ID: 270101  Cd Length: 99  Bit Score: 36.59  E-value: 9.44e-03
                        10        20        30
                ....*....|....*....|....*....|....
gi 7661962  517 EENFEFLIVSSTGQTWHFEAASFEERDAWVQAIE 550
Cdd:cd13284  54 EDSCNFVISNGGTQTFHLKASSEVERQRWVTALE 87
 
Blast search parameters
Data Source: Precalculated data, version = cdd.v.3.16
Preset Options:Database: CDSEARCH/cdd   Low complexity filter: no  Composition Based Adjustment: yes   E-value threshold: 0.01

References:

  • Marchler-Bauer A et al. (2017), "CDD/SPARCLE: functional classification of proteins via subfamily domain architectures.", Nucleic Acids Res.45(D)200-3.
  • Marchler-Bauer A et al. (2015), "CDD: NCBI's conserved domain database.", Nucleic Acids Res.43(D)222-6.
  • Marchler-Bauer A et al. (2011), "CDD: a Conserved Domain Database for the functional annotation of proteins.", Nucleic Acids Res.39(D)225-9.
  • Marchler-Bauer A, Bryant SH (2004), "CD-Search: protein domain annotations on the fly.", Nucleic Acids Res.32(W)327-331.
Help | Disclaimer | Write to the Help Desk
NCBI | NLM | NIH