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Conserved domains on  [gi|158261639|dbj|BAF82997|]
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unnamed protein product, partial [Homo sapiens]

Protein Classification

Graphical summary

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List of domain hits

 Name Accession Description Interval E-value
RasGAP_DAB2IP cd05136
Ras-GTPase Activating Domain of DAB2IP and similar proteins; The DAB2IP family of Ras ...
 289-619 0e+00

Ras-GTPase Activating Domain of DAB2IP and similar proteins; The DAB2IP family of Ras GTPase-activating proteins includes DAB2IP, nGAP, and Syn GAP. Disabled 2 interactive protein, (DAB2IP; also known as ASK-interacting protein 1 (AIP1)), is a member of the GTPase-activating proteins, down-regulates Ras-mediated signal pathways, and mediates TNF-induced activation of ASK1-JNK signaling pathways. The mechanism by which TNF signaling is coupled to DAB2IP is not known.


:

Pssm-ID: 213338  Cd Length: 324  Bit Score: 610.74  E-value: 0e+00
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 158261639 289 RFQTITILPMEQYKESAEFVTSNYTMLCSVLEPVISVRNKEELACALVHILQSTGRAKDFLTDLVMSEVDRCgEHDVLIF 368
Cdd:cd05136    1 RYQSVDILPLEVYKEFLEYLTNNYLDLCEVLEPVLSVKAKEELATALVHILQSTGKAKEFLTDLVMAEVDRL-DDEHLIF 79

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 158261639 369 RENTIATKSIEEYLKLVGQQYLHDALGEFIKALYESDENCEVDPSKCSSS-ELIDHQSNLKMCCELAFCKIINSYCVFPR 447
Cdd:cd05136   80 RGNTLATKAMEAYLKLVGQKYLQETLGEFIRALYESEEDCEVDPSKCPPSaSLSRNQANLRRSVELAWCKILSSHCVFPR 159

                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 158261639 448 ELKEVFASWKQQCLNRGKQDISERLISASLFLRFLCPAIMSPSLFNLMQEYPDDRTSRTLTLIAKVIQNLANFAKFGNKE 527
Cdd:cd05136  160 ELREVFSSWRERLEERGREDIADRLISASLFLRFLCPAILSPSLFNLTQEYPSERAARNLTLIAKVIQNLANFTRFGGKE 239

                        250       260       270       280       290       300       310       320
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 158261639 528 EYMAFMNDFLEHEWGGMKRFLLEISNPDTISNTPGFDGYIDLGRELSVLHSLLWEVVSQLDkgensflQATVAKLGPLPR 607
Cdd:cd05136  240 EYMEFMNDFVEQEWPNMKQFLQEISSPSPSSNSSDFDGYIDLGRELSLLHSLLVEIISKLN-------QTTLDKLGPLPR 312

                        330
                 ....*....|..
gi 158261639 608 VLADITKSLTNP 619
Cdd:cd05136  313 ILNDITEALRNP 324
DUF3498 super family cl26404
Domain of unknown function (DUF3498); This presumed domain is functionally uncharacterized. ...
 609-990 4.22e-140

Domain of unknown function (DUF3498); This presumed domain is functionally uncharacterized. This domain is found in eukaryotes. This domain is typically between 433 to 538 amino acids in length. This domain is found associated with pfam00616, pfam00168. This domain has two conserved sequence motifs: DLQ and PLSFQNP.


The actual alignment was detected with superfamily member pfam12004:

Pssm-ID: 463427 [Multi-domain]  Cd Length: 511  Bit Score: 429.18  E-value: 4.22e-140
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 158261639  609 LADITKSLTNPTPIQQQLRRFTEHNSSPNVSG-SLSSGLQKIFEDPTD--SDLHKLKSPSQDNTDSYFRGKTLLLvQQAS 685
Cdd:pfam12004   1 LRDITTALTNPTPIQQQLRRFSEHSSSPPVPGrSISSGLQKMFEDPDDglSDFTRLPSPTPENKDLFFVTRPPLL-QPSP 79

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 158261639  686 SQSMTYSEKDERESSLPNG-RSVSLMDLQDTHAAQVEHASVMLDVPIRL--TGSQLSITQVAsIKQLRETQSTPQSAPQV 762
Cdd:pfam12004  80 ARSSSYSDANEPDQQLPNGnKSLSMVDLQDSRSLQGSPSPPLHDAPLNLsqAGSQASVGLRP-AWAARTSQGNPQSAPQV 158

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 158261639  763 RRPLHPALNQ----PGGLQPLSFQNPVYHLNN--PIPAMPKASIDSSLEnlSTASSRSQSNSEDF------KLSGPSNSS 830
Cdd:pfam12004 159 RRPLQTPVTQgtrpQQLLAPLSFQNPVYHMAAglPVSPRGLGSPDSSSE--THSSFSSHSNSEDLssaaanKKSGPSNSS 236

                         250       260       270       280       290       300       310       320
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 158261639  831 M-EDFTKRSTQSedFSRRHTVPDRHIPLALPRQNSTGQAqiRKVDQGGLGA----RAKAPPSLPHSASLRSTGSMSVVSA 905
Cdd:pfam12004 237 YsEDFARRSTEF--TRRQLSLTELQHQPAVPRQNSAGPQ--RRIDQQGLGGppltRGRTPPSLLNSASYPRPSSGSLMSS 312

                         330       340       350       360       370       380       390       400
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 158261639  906 AlvaepVQNGSRSRQQSSSSRESPVPKVRAIQRQQTQQvqSPVDSATMSPVERTAAWVLN-NGQYEEDVEETEQNLDEAK 984
Cdd:pfam12004 313 S-----PDWPPARLRQQSSSSKGDSPETKQRTQHQQVP--SPVNPSTLSPVERTAAWVLNmNGQYEEEESSGPESREELK 385


                  ....*.
gi 158261639  985 HAEKYE 990
Cdd:pfam12004 386 QAEKYE 391
PH_nGAP cd13373
Neuronal growth-associated proteins Pleckstrin homology (PH) domain; nGAP (also called RASAL2 ...
 36-173 1.30e-87

Neuronal growth-associated proteins Pleckstrin homology (PH) domain; nGAP (also called RASAL2/RAS protein activator like-3) is a member of the RasSynGAP family along with DOC-2/DAB2-interacting protein (DAB2IP) and synaptic RasGAP (SynGAP). nGAPs are growth cone markers found in multiple types of neurons. There are many nGAPs including Cap1 (Adenylate cyclase-associated protein 1), Capzb (Capping protein (actin filament) muscle Z-line, beta), Clptm1 (Cleft lip and palate associated transmembrane protein 1), Cotl1 (Coactosin-like 1), Crmp1 (Collapsin response mediator protein 1), Cyfip1 (Cytoplasmic FMR1 interacting protein 1), Fabp7 (Fatty acid binding protein 7, brain), Farp2 (FERM, RhoGEF and pleckstrin domain protein 2), Gap43 (Growth associated protein 43), Gnao1 (Guanine nucleotide binding protein (G protein), alpha activating activity polypeptide O), Gnai2 (Guanine nucleotide binding protein (G protein), alpha inhibiting 2), Pacs1 (Phosphofurin acidic cluster sorting protein 1), Rtn1 (Reticulon 1), Sept2 (Septin 2), Snap25 (Synaptosomal-associated protein 25), Strap (Serine/threonine kinase receptor associated protein), Stx7 (Syntaxin 7), and Tmod2 (Tropomodulin 2). PH domains are only found in eukaryotes. They share little sequence conservation, but all have a common fold, which is electrostatically polarized. 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: 270176  Cd Length: 138  Bit Score: 276.61  E-value: 1.30e-87
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 158261639  36 PFKVPGFFSKRLKGSIKRTKSQSKLDRNTSFRLPSPRSTDDRSRGLPKLKESRSHESLLSPCSTVECLDLGRGEPVSVKP 115
Cdd:cd13373    1 PFKVSGFFSKRLKGSIKRTKSQSKLDRNTSFRLPSLRSADDRSRGLPKLKESRSHESLLSPGSAVEALDLGREEKVSVKP 80

                         90       100       110       120       130
                 ....*....|....*....|....*....|....*....|....*....|....*...
gi 158261639 116 LHSSILGQDFCFEVTYLSGSKCFSCNSASERDKWMENLRRTVQPNKDNCRRAENVLRL 173
Cdd:cd13373   81 LHSSILGQDFCFEVTYSSGSKCFSCSSAAERDKWMENLRRTVQPNKDNCRRAENVLRL 138
C2_SynGAP_like cd04013
C2 domain present in Ras GTPase activating protein (GAP) family; SynGAP, GAP1, RasGAP, and ...
 159-298 4.39e-80

C2 domain present in Ras GTPase activating protein (GAP) family; SynGAP, GAP1, RasGAP, and neurofibromin are all members of the Ras-specific GAP (GTPase-activating protein) family. SynGAP regulates the MAP kinase signaling pathway and is critical for cognition and synapse function. Mutations in this gene causes mental retardation in humans. SynGAP contains a PH-like domain, a C2 domain, and a Ras-GAP domain. C2 domains fold into an 8-standed beta-sandwich that can adopt 2 structural arrangements: Type I and Type II, distinguished by a circular permutation involving their N- and C-terminal beta strands. Many C2 domains are Ca2+-dependent membrane-targeting modules that bind a wide variety of substances including bind phospholipids, inositol polyphosphates, and intracellular proteins. Most C2 domain proteins are either signal transduction enzymes that contain a single C2 domain, such as protein kinase C, or membrane trafficking proteins which contain at least two C2 domains, such as synaptotagmin 1. However, there are a few exceptions to this including RIM isoforms and some splice variants of piccolo/aczonin and intersectin which only have a single C2 domain. C2 domains with a calcium binding region have negatively charged residues, primarily aspartates, that serve as ligands for calcium ions.


:

Pssm-ID: 175980 [Multi-domain]  Cd Length: 146  Bit Score: 256.47  E-value: 4.39e-80
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 158261639 159 PNKDNCRRAENVLRLWIIEAKDLAPKKKYFCELCLDDTLFARTTSKTKADNIFWGEHFEFFSLPPLHSITVHIYKDVEKR 238
Cdd:cd04013    1 PNRDNSRRTENSLKLWIIEAKGLPPKKRYYCELCLDKTLYARTTSKLKTDTLFWGEHFEFSNLPPVSVITVNLYRESDKK 80

                         90       100       110       120       130       140
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 158261639 239 KKKDKNNYVGLVNIPTASVTGRQFVEKWYPVSTPTPNK------GKTGGPSIRIKSRFQTITILPM 298
Cdd:cd04013   81 KKKDKSQLIGTVNIPVTDVSSRQFVEKWYPVSTPKGNGksggkeGKGESPSIRIKARYQSTRVLPL 146
 
Name Accession Description Interval E-value
RasGAP_DAB2IP cd05136
Ras-GTPase Activating Domain of DAB2IP and similar proteins; The DAB2IP family of Ras ...
 289-619 0e+00

Ras-GTPase Activating Domain of DAB2IP and similar proteins; The DAB2IP family of Ras GTPase-activating proteins includes DAB2IP, nGAP, and Syn GAP. Disabled 2 interactive protein, (DAB2IP; also known as ASK-interacting protein 1 (AIP1)), is a member of the GTPase-activating proteins, down-regulates Ras-mediated signal pathways, and mediates TNF-induced activation of ASK1-JNK signaling pathways. The mechanism by which TNF signaling is coupled to DAB2IP is not known.


Pssm-ID: 213338  Cd Length: 324  Bit Score: 610.74  E-value: 0e+00
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 158261639 289 RFQTITILPMEQYKESAEFVTSNYTMLCSVLEPVISVRNKEELACALVHILQSTGRAKDFLTDLVMSEVDRCgEHDVLIF 368
Cdd:cd05136    1 RYQSVDILPLEVYKEFLEYLTNNYLDLCEVLEPVLSVKAKEELATALVHILQSTGKAKEFLTDLVMAEVDRL-DDEHLIF 79

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 158261639 369 RENTIATKSIEEYLKLVGQQYLHDALGEFIKALYESDENCEVDPSKCSSS-ELIDHQSNLKMCCELAFCKIINSYCVFPR 447
Cdd:cd05136   80 RGNTLATKAMEAYLKLVGQKYLQETLGEFIRALYESEEDCEVDPSKCPPSaSLSRNQANLRRSVELAWCKILSSHCVFPR 159

                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 158261639 448 ELKEVFASWKQQCLNRGKQDISERLISASLFLRFLCPAIMSPSLFNLMQEYPDDRTSRTLTLIAKVIQNLANFAKFGNKE 527
Cdd:cd05136  160 ELREVFSSWRERLEERGREDIADRLISASLFLRFLCPAILSPSLFNLTQEYPSERAARNLTLIAKVIQNLANFTRFGGKE 239

                        250       260       270       280       290       300       310       320
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 158261639 528 EYMAFMNDFLEHEWGGMKRFLLEISNPDTISNTPGFDGYIDLGRELSVLHSLLWEVVSQLDkgensflQATVAKLGPLPR 607
Cdd:cd05136  240 EYMEFMNDFVEQEWPNMKQFLQEISSPSPSSNSSDFDGYIDLGRELSLLHSLLVEIISKLN-------QTTLDKLGPLPR 312

                        330
                 ....*....|..
gi 158261639 608 VLADITKSLTNP 619
Cdd:cd05136  313 ILNDITEALRNP 324
DUF3498 pfam12004
Domain of unknown function (DUF3498); This presumed domain is functionally uncharacterized. ...
 609-990 4.22e-140

Domain of unknown function (DUF3498); This presumed domain is functionally uncharacterized. This domain is found in eukaryotes. This domain is typically between 433 to 538 amino acids in length. This domain is found associated with pfam00616, pfam00168. This domain has two conserved sequence motifs: DLQ and PLSFQNP.


Pssm-ID: 463427 [Multi-domain]  Cd Length: 511  Bit Score: 429.18  E-value: 4.22e-140
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 158261639  609 LADITKSLTNPTPIQQQLRRFTEHNSSPNVSG-SLSSGLQKIFEDPTD--SDLHKLKSPSQDNTDSYFRGKTLLLvQQAS 685
Cdd:pfam12004   1 LRDITTALTNPTPIQQQLRRFSEHSSSPPVPGrSISSGLQKMFEDPDDglSDFTRLPSPTPENKDLFFVTRPPLL-QPSP 79

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 158261639  686 SQSMTYSEKDERESSLPNG-RSVSLMDLQDTHAAQVEHASVMLDVPIRL--TGSQLSITQVAsIKQLRETQSTPQSAPQV 762
Cdd:pfam12004  80 ARSSSYSDANEPDQQLPNGnKSLSMVDLQDSRSLQGSPSPPLHDAPLNLsqAGSQASVGLRP-AWAARTSQGNPQSAPQV 158

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 158261639  763 RRPLHPALNQ----PGGLQPLSFQNPVYHLNN--PIPAMPKASIDSSLEnlSTASSRSQSNSEDF------KLSGPSNSS 830
Cdd:pfam12004 159 RRPLQTPVTQgtrpQQLLAPLSFQNPVYHMAAglPVSPRGLGSPDSSSE--THSSFSSHSNSEDLssaaanKKSGPSNSS 236

                         250       260       270       280       290       300       310       320
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 158261639  831 M-EDFTKRSTQSedFSRRHTVPDRHIPLALPRQNSTGQAqiRKVDQGGLGA----RAKAPPSLPHSASLRSTGSMSVVSA 905
Cdd:pfam12004 237 YsEDFARRSTEF--TRRQLSLTELQHQPAVPRQNSAGPQ--RRIDQQGLGGppltRGRTPPSLLNSASYPRPSSGSLMSS 312

                         330       340       350       360       370       380       390       400
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 158261639  906 AlvaepVQNGSRSRQQSSSSRESPVPKVRAIQRQQTQQvqSPVDSATMSPVERTAAWVLN-NGQYEEDVEETEQNLDEAK 984
Cdd:pfam12004 313 S-----PDWPPARLRQQSSSSKGDSPETKQRTQHQQVP--SPVNPSTLSPVERTAAWVLNmNGQYEEEESSGPESREELK 385


                  ....*.
gi 158261639  985 HAEKYE 990
Cdd:pfam12004 386 QAEKYE 391
RasGAP smart00323
GTPase-activator protein for Ras-like GTPases; All alpha-helical domain that accelerates the ...
 282-620 2.97e-128

GTPase-activator protein for Ras-like GTPases; All alpha-helical domain that accelerates the GTPase activity of Ras, thereby "switching" it into an "off" position. Improved domain limits from structure.


Pssm-ID: 214617  Cd Length: 344  Bit Score: 392.06  E-value: 2.97e-128
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 158261639   282 PSIRIKSRFQTITILPMEQYKESAEFVTSNY-TMLCSVLEPVISVRNKEELACALVHILQSTGRAKDFLTDLVMSEVDRC 360
Cdd:smart00323   7 GSLRLKTVYTTDFILPSEYYEELLELLLFSLdLSLASALSEVCSGLDKDELATKLVRLFLRRGRGHPFLRALIDPEVERT 86

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 158261639   361 GEhDVLIFRENTIATKSIEEYLKLVGQQYLHDALGEFIKALYESDENCEVDPSKCSSSELIDHQSNLKMCCELAFCKIIN 440
Cdd:smart00323  87 DD-PNTIFRGNSLATKSMEVYMKLVGNQYLHTTLKPVLKKIVESKKSCEVDPAKLEGEDLETNLENLLQYVERLFDAIIN 165

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 158261639   441 SYCVFPRELKEVFASWKQQCLNR-GKQDISERLISASLFLRFLCPAIMSPSLFNLMQEYPDDRTSRTLTLIAKVIQNLAN 519
Cdd:smart00323 166 SSDRLPYGLRDICKQLRQAAEKRfPDADVIYKAVSSFVFLRFFCPAIVSPKLFNLVDEHPDPTTRRTLTLIAKVLQNLAN 245

                          250       260       270       280       290       300       310       320
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 158261639   520 FAKFGNKEEYMAFMNDFLEHEWGGMKRFLLEISNPDTISNTPGFDGYIDLGRELSVLHSLLWEVVSQLDKGENSflQATV 599
Cdd:smart00323 246 LSEFGSKEPWMEPLNDFLLSHKDRVKDFLDELSSVPEILVDKVSDSTTISGRELSLLHSLLLENGDALKRELNN--EDPL 323

                          330       340
                   ....*....|....*....|.
gi 158261639   600 AKLGPLPRVLADITKSLTNPT 620
Cdd:smart00323 324 GKLLFKLRYFGLTTHELTYGK 344
PH_nGAP cd13373
Neuronal growth-associated proteins Pleckstrin homology (PH) domain; nGAP (also called RASAL2 ...
 36-173 1.30e-87

Neuronal growth-associated proteins Pleckstrin homology (PH) domain; nGAP (also called RASAL2/RAS protein activator like-3) is a member of the RasSynGAP family along with DOC-2/DAB2-interacting protein (DAB2IP) and synaptic RasGAP (SynGAP). nGAPs are growth cone markers found in multiple types of neurons. There are many nGAPs including Cap1 (Adenylate cyclase-associated protein 1), Capzb (Capping protein (actin filament) muscle Z-line, beta), Clptm1 (Cleft lip and palate associated transmembrane protein 1), Cotl1 (Coactosin-like 1), Crmp1 (Collapsin response mediator protein 1), Cyfip1 (Cytoplasmic FMR1 interacting protein 1), Fabp7 (Fatty acid binding protein 7, brain), Farp2 (FERM, RhoGEF and pleckstrin domain protein 2), Gap43 (Growth associated protein 43), Gnao1 (Guanine nucleotide binding protein (G protein), alpha activating activity polypeptide O), Gnai2 (Guanine nucleotide binding protein (G protein), alpha inhibiting 2), Pacs1 (Phosphofurin acidic cluster sorting protein 1), Rtn1 (Reticulon 1), Sept2 (Septin 2), Snap25 (Synaptosomal-associated protein 25), Strap (Serine/threonine kinase receptor associated protein), Stx7 (Syntaxin 7), and Tmod2 (Tropomodulin 2). PH domains are only found in eukaryotes. They share little sequence conservation, but all have a common fold, which is electrostatically polarized. 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: 270176  Cd Length: 138  Bit Score: 276.61  E-value: 1.30e-87
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 158261639  36 PFKVPGFFSKRLKGSIKRTKSQSKLDRNTSFRLPSPRSTDDRSRGLPKLKESRSHESLLSPCSTVECLDLGRGEPVSVKP 115
Cdd:cd13373    1 PFKVSGFFSKRLKGSIKRTKSQSKLDRNTSFRLPSLRSADDRSRGLPKLKESRSHESLLSPGSAVEALDLGREEKVSVKP 80

                         90       100       110       120       130
                 ....*....|....*....|....*....|....*....|....*....|....*...
gi 158261639 116 LHSSILGQDFCFEVTYLSGSKCFSCNSASERDKWMENLRRTVQPNKDNCRRAENVLRL 173
Cdd:cd13373   81 LHSSILGQDFCFEVTYSSGSKCFSCSSAAERDKWMENLRRTVQPNKDNCRRAENVLRL 138
C2_SynGAP_like cd04013
C2 domain present in Ras GTPase activating protein (GAP) family; SynGAP, GAP1, RasGAP, and ...
 159-298 4.39e-80

C2 domain present in Ras GTPase activating protein (GAP) family; SynGAP, GAP1, RasGAP, and neurofibromin are all members of the Ras-specific GAP (GTPase-activating protein) family. SynGAP regulates the MAP kinase signaling pathway and is critical for cognition and synapse function. Mutations in this gene causes mental retardation in humans. SynGAP contains a PH-like domain, a C2 domain, and a Ras-GAP domain. C2 domains fold into an 8-standed beta-sandwich that can adopt 2 structural arrangements: Type I and Type II, distinguished by a circular permutation involving their N- and C-terminal beta strands. Many C2 domains are Ca2+-dependent membrane-targeting modules that bind a wide variety of substances including bind phospholipids, inositol polyphosphates, and intracellular proteins. Most C2 domain proteins are either signal transduction enzymes that contain a single C2 domain, such as protein kinase C, or membrane trafficking proteins which contain at least two C2 domains, such as synaptotagmin 1. However, there are a few exceptions to this including RIM isoforms and some splice variants of piccolo/aczonin and intersectin which only have a single C2 domain. C2 domains with a calcium binding region have negatively charged residues, primarily aspartates, that serve as ligands for calcium ions.


Pssm-ID: 175980 [Multi-domain]  Cd Length: 146  Bit Score: 256.47  E-value: 4.39e-80
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 158261639 159 PNKDNCRRAENVLRLWIIEAKDLAPKKKYFCELCLDDTLFARTTSKTKADNIFWGEHFEFFSLPPLHSITVHIYKDVEKR 238
Cdd:cd04013    1 PNRDNSRRTENSLKLWIIEAKGLPPKKRYYCELCLDKTLYARTTSKLKTDTLFWGEHFEFSNLPPVSVITVNLYRESDKK 80

                         90       100       110       120       130       140
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 158261639 239 KKKDKNNYVGLVNIPTASVTGRQFVEKWYPVSTPTPNK------GKTGGPSIRIKSRFQTITILPM 298
Cdd:cd04013   81 KKKDKSQLIGTVNIPVTDVSSRQFVEKWYPVSTPKGNGksggkeGKGESPSIRIKARYQSTRVLPL 146
RasGAP pfam00616
GTPase-activator protein for Ras-like GTPase; All alpha-helical domain that accelerates the ...
 348-519 8.82e-30

GTPase-activator protein for Ras-like GTPase; All alpha-helical domain that accelerates the GTPase activity of Ras, thereby "switching" it into an "off" position.


Pssm-ID: 459871  Cd Length: 207  Bit Score: 117.39  E-value: 8.82e-30
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 158261639  348 FLTDLVMSEVDRCGEhDVLIFRENTIATKSIEEYLKL-VGQQYLHDALGEFIKALYESDE-NCEVDPSKC---------- 415
Cdd:pfam00616   1 LISELIEEEIESSDN-PNDLLRGNSLVSKLLETYNRRpRGQEYLKKVLGPLVRKIIEDEDlDLESDPRKIyeslinqeel 79

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 158261639  416 ---------------------SSSELIDHQSNLKMCCELAFCKIINSYCVFPREL----KEVFASWKQQCLNRGKQDISE 470
Cdd:pfam00616  80 ktgrsdlprdvspeeaiedpeVRQIFEDNLQKLRELADEFLDAIYSSLNQLPYGIryicKQLYELLEEKFPDASEEEILN 159

                         170       180       190       200
                  ....*....|....*....|....*....|....*....|....*....
gi 158261639  471 rLISASLFLRFLCPAIMSPSLFNLMQEYPDDRTSRTLTLIAKVIQNLAN 519
Cdd:pfam00616 160 -AIGGFLFLRFFCPAIVNPDLFGLVDHQISPKQRRNLTLIAKVLQNLAN 207
C2 pfam00168
C2 domain;
169-269 8.39e-10

C2 domain;


Pssm-ID: 425499 [Multi-domain]  Cd Length: 104  Bit Score: 56.94  E-value: 8.39e-10
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 158261639  169 NVLRLWIIEAKDLAPKKKY-----FCELCL-DDTLFARTTSKTKADNIFWGEHFEfFSLPPLHSITVHIYkdVEKRKKKD 242
Cdd:pfam00168   1 GRLTVTVIEAKNLPPKDGNgtsdpYVKVYLlDGKQKKKTKVVKNTLNPVWNETFT-FSVPDPENAVLEIE--VYDYDRFG 77

                          90       100
                  ....*....|....*....|....*..
gi 158261639  243 KNNYVGLVNIPTASVTGRQFVEKWYPV 269
Cdd:pfam00168  78 RDDFIGEVRIPLSELDSGEGLDGWYPL 104
C2 smart00239
Protein kinase C conserved region 2 (CalB); Ca2+-binding motif present in phospholipases, ...
 170-266 7.08e-09

Protein kinase C conserved region 2 (CalB); Ca2+-binding motif present in phospholipases, protein kinases C, and synaptotagmins (among others). Some do not appear to contain Ca2+-binding sites. Particular C2s appear to bind phospholipids, inositol polyphosphates, and intracellular proteins. Unusual occurrence in perforin. Synaptotagmin and PLC C2s are permuted in sequence with respect to N- and C-terminal beta strands. SMART detects C2 domains using one or both of two profiles.


Pssm-ID: 214577 [Multi-domain]  Cd Length: 101  Bit Score: 54.03  E-value: 7.08e-09
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 158261639   170 VLRLWIIEAKDLAPKKKY-----FCELCLD--DTLFARTTSKTKADNIFWGEHFEFFSLPP-LHSITVHIYKDvekrKKK 241
Cdd:smart00239   1 TLTVKIISARNLPPKDKGgksdpYVKVSLDgdPKEKKKTKVVKNTLNPVWNETFEFEVPPPeLAELEIEVYDK----DRF 76

                           90       100
                   ....*....|....*....|....*
gi 158261639   242 DKNNYVGLVNIPTASVTGRQFVEKW 266
Cdd:smart00239  77 GRDDFIGQVTIPLSDLLLGGRHEKL 101
PH smart00233
Pleckstrin homology domain; Domain commonly found in eukaryotic signalling proteins. The ...
 113-158 1.81e-03

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


Pssm-ID: 214574 [Multi-domain]  Cd Length: 102  Bit Score: 38.68  E-value: 1.81e-03
                           10        20        30        40
                   ....*....|....*....|....*....|....*....|....*..
gi 158261639   113 VKPLHSSILGQDFCFEVTYLSG-SKCFSCNSASERDKWMENLRRTVQ 158
Cdd:smart00233  56 REAPDPDSSKKPHCFEIKTSDRkTLLLQAESEEEREKWVEALRKAIA 102
 
Name Accession Description Interval E-value
RasGAP_DAB2IP cd05136
Ras-GTPase Activating Domain of DAB2IP and similar proteins; The DAB2IP family of Ras ...
 289-619 0e+00

Ras-GTPase Activating Domain of DAB2IP and similar proteins; The DAB2IP family of Ras GTPase-activating proteins includes DAB2IP, nGAP, and Syn GAP. Disabled 2 interactive protein, (DAB2IP; also known as ASK-interacting protein 1 (AIP1)), is a member of the GTPase-activating proteins, down-regulates Ras-mediated signal pathways, and mediates TNF-induced activation of ASK1-JNK signaling pathways. The mechanism by which TNF signaling is coupled to DAB2IP is not known.


Pssm-ID: 213338  Cd Length: 324  Bit Score: 610.74  E-value: 0e+00
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 158261639 289 RFQTITILPMEQYKESAEFVTSNYTMLCSVLEPVISVRNKEELACALVHILQSTGRAKDFLTDLVMSEVDRCgEHDVLIF 368
Cdd:cd05136    1 RYQSVDILPLEVYKEFLEYLTNNYLDLCEVLEPVLSVKAKEELATALVHILQSTGKAKEFLTDLVMAEVDRL-DDEHLIF 79

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 158261639 369 RENTIATKSIEEYLKLVGQQYLHDALGEFIKALYESDENCEVDPSKCSSS-ELIDHQSNLKMCCELAFCKIINSYCVFPR 447
Cdd:cd05136   80 RGNTLATKAMEAYLKLVGQKYLQETLGEFIRALYESEEDCEVDPSKCPPSaSLSRNQANLRRSVELAWCKILSSHCVFPR 159

                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 158261639 448 ELKEVFASWKQQCLNRGKQDISERLISASLFLRFLCPAIMSPSLFNLMQEYPDDRTSRTLTLIAKVIQNLANFAKFGNKE 527
Cdd:cd05136  160 ELREVFSSWRERLEERGREDIADRLISASLFLRFLCPAILSPSLFNLTQEYPSERAARNLTLIAKVIQNLANFTRFGGKE 239

                        250       260       270       280       290       300       310       320
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 158261639 528 EYMAFMNDFLEHEWGGMKRFLLEISNPDTISNTPGFDGYIDLGRELSVLHSLLWEVVSQLDkgensflQATVAKLGPLPR 607
Cdd:cd05136  240 EYMEFMNDFVEQEWPNMKQFLQEISSPSPSSNSSDFDGYIDLGRELSLLHSLLVEIISKLN-------QTTLDKLGPLPR 312

                        330
                 ....*....|..
gi 158261639 608 VLADITKSLTNP 619
Cdd:cd05136  313 ILNDITEALRNP 324
DUF3498 pfam12004
Domain of unknown function (DUF3498); This presumed domain is functionally uncharacterized. ...
 609-990 4.22e-140

Domain of unknown function (DUF3498); This presumed domain is functionally uncharacterized. This domain is found in eukaryotes. This domain is typically between 433 to 538 amino acids in length. This domain is found associated with pfam00616, pfam00168. This domain has two conserved sequence motifs: DLQ and PLSFQNP.


Pssm-ID: 463427 [Multi-domain]  Cd Length: 511  Bit Score: 429.18  E-value: 4.22e-140
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 158261639  609 LADITKSLTNPTPIQQQLRRFTEHNSSPNVSG-SLSSGLQKIFEDPTD--SDLHKLKSPSQDNTDSYFRGKTLLLvQQAS 685
Cdd:pfam12004   1 LRDITTALTNPTPIQQQLRRFSEHSSSPPVPGrSISSGLQKMFEDPDDglSDFTRLPSPTPENKDLFFVTRPPLL-QPSP 79

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 158261639  686 SQSMTYSEKDERESSLPNG-RSVSLMDLQDTHAAQVEHASVMLDVPIRL--TGSQLSITQVAsIKQLRETQSTPQSAPQV 762
Cdd:pfam12004  80 ARSSSYSDANEPDQQLPNGnKSLSMVDLQDSRSLQGSPSPPLHDAPLNLsqAGSQASVGLRP-AWAARTSQGNPQSAPQV 158

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 158261639  763 RRPLHPALNQ----PGGLQPLSFQNPVYHLNN--PIPAMPKASIDSSLEnlSTASSRSQSNSEDF------KLSGPSNSS 830
Cdd:pfam12004 159 RRPLQTPVTQgtrpQQLLAPLSFQNPVYHMAAglPVSPRGLGSPDSSSE--THSSFSSHSNSEDLssaaanKKSGPSNSS 236

                         250       260       270       280       290       300       310       320
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 158261639  831 M-EDFTKRSTQSedFSRRHTVPDRHIPLALPRQNSTGQAqiRKVDQGGLGA----RAKAPPSLPHSASLRSTGSMSVVSA 905
Cdd:pfam12004 237 YsEDFARRSTEF--TRRQLSLTELQHQPAVPRQNSAGPQ--RRIDQQGLGGppltRGRTPPSLLNSASYPRPSSGSLMSS 312

                         330       340       350       360       370       380       390       400
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 158261639  906 AlvaepVQNGSRSRQQSSSSRESPVPKVRAIQRQQTQQvqSPVDSATMSPVERTAAWVLN-NGQYEEDVEETEQNLDEAK 984
Cdd:pfam12004 313 S-----PDWPPARLRQQSSSSKGDSPETKQRTQHQQVP--SPVNPSTLSPVERTAAWVLNmNGQYEEEESSGPESREELK 385


                  ....*.
gi 158261639  985 HAEKYE 990
Cdd:pfam12004 386 QAEKYE 391
RasGAP smart00323
GTPase-activator protein for Ras-like GTPases; All alpha-helical domain that accelerates the ...
 282-620 2.97e-128

GTPase-activator protein for Ras-like GTPases; All alpha-helical domain that accelerates the GTPase activity of Ras, thereby "switching" it into an "off" position. Improved domain limits from structure.


Pssm-ID: 214617  Cd Length: 344  Bit Score: 392.06  E-value: 2.97e-128
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 158261639   282 PSIRIKSRFQTITILPMEQYKESAEFVTSNY-TMLCSVLEPVISVRNKEELACALVHILQSTGRAKDFLTDLVMSEVDRC 360
Cdd:smart00323   7 GSLRLKTVYTTDFILPSEYYEELLELLLFSLdLSLASALSEVCSGLDKDELATKLVRLFLRRGRGHPFLRALIDPEVERT 86

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 158261639   361 GEhDVLIFRENTIATKSIEEYLKLVGQQYLHDALGEFIKALYESDENCEVDPSKCSSSELIDHQSNLKMCCELAFCKIIN 440
Cdd:smart00323  87 DD-PNTIFRGNSLATKSMEVYMKLVGNQYLHTTLKPVLKKIVESKKSCEVDPAKLEGEDLETNLENLLQYVERLFDAIIN 165

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 158261639   441 SYCVFPRELKEVFASWKQQCLNR-GKQDISERLISASLFLRFLCPAIMSPSLFNLMQEYPDDRTSRTLTLIAKVIQNLAN 519
Cdd:smart00323 166 SSDRLPYGLRDICKQLRQAAEKRfPDADVIYKAVSSFVFLRFFCPAIVSPKLFNLVDEHPDPTTRRTLTLIAKVLQNLAN 245

                          250       260       270       280       290       300       310       320
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 158261639   520 FAKFGNKEEYMAFMNDFLEHEWGGMKRFLLEISNPDTISNTPGFDGYIDLGRELSVLHSLLWEVVSQLDKGENSflQATV 599
Cdd:smart00323 246 LSEFGSKEPWMEPLNDFLLSHKDRVKDFLDELSSVPEILVDKVSDSTTISGRELSLLHSLLLENGDALKRELNN--EDPL 323

                          330       340
                   ....*....|....*....|.
gi 158261639   600 AKLGPLPRVLADITKSLTNPT 620
Cdd:smart00323 324 GKLLFKLRYFGLTTHELTYGK 344
PH_nGAP cd13373
Neuronal growth-associated proteins Pleckstrin homology (PH) domain; nGAP (also called RASAL2 ...
 36-173 1.30e-87

Neuronal growth-associated proteins Pleckstrin homology (PH) domain; nGAP (also called RASAL2/RAS protein activator like-3) is a member of the RasSynGAP family along with DOC-2/DAB2-interacting protein (DAB2IP) and synaptic RasGAP (SynGAP). nGAPs are growth cone markers found in multiple types of neurons. There are many nGAPs including Cap1 (Adenylate cyclase-associated protein 1), Capzb (Capping protein (actin filament) muscle Z-line, beta), Clptm1 (Cleft lip and palate associated transmembrane protein 1), Cotl1 (Coactosin-like 1), Crmp1 (Collapsin response mediator protein 1), Cyfip1 (Cytoplasmic FMR1 interacting protein 1), Fabp7 (Fatty acid binding protein 7, brain), Farp2 (FERM, RhoGEF and pleckstrin domain protein 2), Gap43 (Growth associated protein 43), Gnao1 (Guanine nucleotide binding protein (G protein), alpha activating activity polypeptide O), Gnai2 (Guanine nucleotide binding protein (G protein), alpha inhibiting 2), Pacs1 (Phosphofurin acidic cluster sorting protein 1), Rtn1 (Reticulon 1), Sept2 (Septin 2), Snap25 (Synaptosomal-associated protein 25), Strap (Serine/threonine kinase receptor associated protein), Stx7 (Syntaxin 7), and Tmod2 (Tropomodulin 2). PH domains are only found in eukaryotes. They share little sequence conservation, but all have a common fold, which is electrostatically polarized. 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: 270176  Cd Length: 138  Bit Score: 276.61  E-value: 1.30e-87
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 158261639  36 PFKVPGFFSKRLKGSIKRTKSQSKLDRNTSFRLPSPRSTDDRSRGLPKLKESRSHESLLSPCSTVECLDLGRGEPVSVKP 115
Cdd:cd13373    1 PFKVSGFFSKRLKGSIKRTKSQSKLDRNTSFRLPSLRSADDRSRGLPKLKESRSHESLLSPGSAVEALDLGREEKVSVKP 80

                         90       100       110       120       130
                 ....*....|....*....|....*....|....*....|....*....|....*...
gi 158261639 116 LHSSILGQDFCFEVTYLSGSKCFSCNSASERDKWMENLRRTVQPNKDNCRRAENVLRL 173
Cdd:cd13373   81 LHSSILGQDFCFEVTYSSGSKCFSCSSAAERDKWMENLRRTVQPNKDNCRRAENVLRL 138
PH_SynGAP cd13375
Synaptic Ras-GTPase activating protein Pleckstrin homology (PH) domain; SynGAP is a member of ...
 34-217 4.17e-87

Synaptic Ras-GTPase activating protein Pleckstrin homology (PH) domain; SynGAP is a member of the RasSynGAP family along with DOC-2/DAB2-interacting protein (DAB2IP) and neuronal growth-associated protein (nGAP/RASAL2). SynGAP, a neuronal Ras-GAP, has been shown display both Ras-GAP activity and Ras-related protein (Rap)-GAP activity. Saccharomyces cerevisiae Bud2 and GAP1 members CAPRI (Ca2+-promoted Ras inactivator) and RASAL (Ras-GTPase-activating-like protein) also possess this dual activity. Human DOC-2/DAB2-interacting protein (DAB2IP) is encoded by a tumor suppressor gene and a newly recognized member of the Ras-GTPase-activating family. Members here include mammals, amphibians, and bony fish. 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: 270178  Cd Length: 189  Bit Score: 277.35  E-value: 4.17e-87
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 158261639  34 TSPFK-VPGFFSKRLKGSIKRTKSQSKLDRNTSFR--LPSPRSTD-DRSRGLPKLKESRSHESLLSPCSTVECLDLGRGE 109
Cdd:cd13375    2 TAPFRpSQGFLSRRLKSSIKRTKSQPKLDRTSSFRqiLPRFRSADhDRARLMQSFKESHSHESLLSPSSAAEALDLNLDE 81

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 158261639 110 PVSVKPLHSSILGQDFCFEVTYLSGSKCFSCNSASERDKWMENLRRTVQPNKDNCRRAENVLRLWIIEAKDLAPKKKYFC 189
Cdd:cd13375   82 DSIIKPVHSSILGQEFCFEVTTASGTKCFACRSAAERDKWIENLQRAVKPNKDNSRRVDNVLKLWIIEARELPPKKRYYC 161

                        170       180
                 ....*....|....*....|....*...
gi 158261639 190 ELCLDDTLFARTTSKTKADNIFWGEHFE 217
Cdd:cd13375  162 ELCLDDMLYARTTSKPRTDTVFWGEHFE 189
PH_DAB2IP cd13376
DOC-2/Disabled homolog 2-interacting protein Pleckstrin homology (PH) domain; DAB2IP (also ...
 39-217 3.69e-83

DOC-2/Disabled homolog 2-interacting protein Pleckstrin homology (PH) domain; DAB2IP (also called AIP1/ASK1-interacting protein-1 and DIP1/2) is a member of the RasSynGAP family along with Synaptic Ras-GTPase activating protein (SynGAP) and neuronal growth-associated protein (nGAP/RASAL2). DAB2IP is a critical component of many signal transduction pathways mediated by Ras and tumor necrosis factors including apoptosis pathways, and it is involved in the formation of many types of tumors. DAB2IP participates in regulation of gene expression and pluripotency of cells. Human DAB2IP is expressed in the adrenal gland, pancreas, endocardium, stomach, kidney, testis, small intestine, liver, trachea, skin, ovary, endometrium, lung, esophagus and bladder. No expression was observed in the cerebrum, parotid gland, thymus, thyroid gland and spleen. 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: 270179  Cd Length: 182  Bit Score: 266.57  E-value: 3.69e-83
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 158261639  39 VPGFFSKRLKGSIKRTKSQSKLDRNTSFR--LPSPRSTD-DRSRGLPKLKESRSHESLLSPCSTVECLDLGRGEPVSVKP 115
Cdd:cd13376    1 VTGFLSRRLKGSIKRTKSQPKLDRNSSFRhiLPGFRSVDnERSHLMPRLKESRSHESLLSPSSAVEALDLSMEEEVVIKP 80

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 158261639 116 LHSSILGQDFCFEVTYLSGSKCFSCNSASERDKWMENLRRTVQPNKDNCRRAENVLRLWIIEAKDLAPKKKYFCELCLDD 195
Cdd:cd13376   81 VHSSILGQDYCFEVTTSSGSKCFSCRSAAERDKWMENLRRAVHPNKDNSRRVENMLKLWIIEAKDLPAKKKYLCELCLDD 160

                        170       180
                 ....*....|....*....|..
gi 158261639 196 TLFARTTSKTKADNIFWGEHFE 217
Cdd:cd13376  161 VLYARTTCKLKTDNVFWGEHFE 182
C2_SynGAP_like cd04013
C2 domain present in Ras GTPase activating protein (GAP) family; SynGAP, GAP1, RasGAP, and ...
 159-298 4.39e-80

C2 domain present in Ras GTPase activating protein (GAP) family; SynGAP, GAP1, RasGAP, and neurofibromin are all members of the Ras-specific GAP (GTPase-activating protein) family. SynGAP regulates the MAP kinase signaling pathway and is critical for cognition and synapse function. Mutations in this gene causes mental retardation in humans. SynGAP contains a PH-like domain, a C2 domain, and a Ras-GAP domain. C2 domains fold into an 8-standed beta-sandwich that can adopt 2 structural arrangements: Type I and Type II, distinguished by a circular permutation involving their N- and C-terminal beta strands. Many C2 domains are Ca2+-dependent membrane-targeting modules that bind a wide variety of substances including bind phospholipids, inositol polyphosphates, and intracellular proteins. Most C2 domain proteins are either signal transduction enzymes that contain a single C2 domain, such as protein kinase C, or membrane trafficking proteins which contain at least two C2 domains, such as synaptotagmin 1. However, there are a few exceptions to this including RIM isoforms and some splice variants of piccolo/aczonin and intersectin which only have a single C2 domain. C2 domains with a calcium binding region have negatively charged residues, primarily aspartates, that serve as ligands for calcium ions.


Pssm-ID: 175980 [Multi-domain]  Cd Length: 146  Bit Score: 256.47  E-value: 4.39e-80
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 158261639 159 PNKDNCRRAENVLRLWIIEAKDLAPKKKYFCELCLDDTLFARTTSKTKADNIFWGEHFEFFSLPPLHSITVHIYKDVEKR 238
Cdd:cd04013    1 PNRDNSRRTENSLKLWIIEAKGLPPKKRYYCELCLDKTLYARTTSKLKTDTLFWGEHFEFSNLPPVSVITVNLYRESDKK 80

                         90       100       110       120       130       140
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 158261639 239 KKKDKNNYVGLVNIPTASVTGRQFVEKWYPVSTPTPNK------GKTGGPSIRIKSRFQTITILPM 298
Cdd:cd04013   81 KKKDKSQLIGTVNIPVTDVSSRQFVEKWYPVSTPKGNGksggkeGKGESPSIRIKARYQSTRVLPL 146
RasGAP cd04519
Ras GTPase Activating Domain; RasGAP functions as an enhancer of the hydrolysis of GTP that is ...
 299-553 1.07e-74

Ras GTPase Activating Domain; RasGAP functions as an enhancer of the hydrolysis of GTP that is bound to Ras-GTPases. Proteins having a RasGAP domain include p120GAP, IQGAP, Rab5-activating protein 6, and Neurofibromin, among others. Although the Rho (Ras homolog) GTPases are most closely related to members of the Ras family, RhoGAP and RasGAP exhibit no similarity at their amino acid sequence level. RasGTPases function as molecular switches in a large number of signaling pathways. They are in the on state when bound to GTP, and in the off state when bound to GDP. The RasGAP domain speeds up the hydrolysis of GTP in Ras-like proteins acting as a negative regulator.


Pssm-ID: 213328  Cd Length: 256  Bit Score: 246.25  E-value: 1.07e-74
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 158261639 299 EQYKESAEFVTSNYTMLCSVLEPVISVRNKEELACALVHILQSTGRAKDFLTDLVMSEVDRCgEHDVLIFRENTIATKSI 378
Cdd:cd04519    1 EEYRLLSLLLTESPLALLRELSQVLPVKDKEEVATALLRIFESRGLALEFLRYLVRSEVKNT-KNPNTLFRGNSLATKLL 79

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 158261639 379 EEYLKLVGQQYLHDALGEFIKALYESDENCEVDPSKCSSSELIDHQSNLKMCCELAFCKIINSYCVFPRELKEVFASWKQ 458
Cdd:cd04519   80 DQYMKLVGQEYLKETLSPLIREILESKESCEIDTKLPVGEDLEENLENLLELVNKLVDRILSSLDRLPPELRYVFKILRE 159

                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 158261639 459 --QCLNRGKQDISERLISASLFLRFLCPAIMSPSLFNLMQEYPDDRTSRTLTLIAKVIQNLANFAKFGNKEEYMAFMNDF 536
Cdd:cd04519  160 flAERFPEEPDEAYQAVSGFLFLRFICPAIVSPELFGLVPDEPSEQARRNLTLISKVLQSLANGVEFGDKEPFMKPLNDF 239

                        250
                 ....*....|....*..
gi 158261639 537 LEHEWGGMKRFLLEISN 553
Cdd:cd04519  240 IKSNKPKLKQFLDELSS 256
PH_RasSynGAP-like cd13262
Synaptic Ras-GTPase activating protein family Pleckstrin homology (PH) domain; The RasSynGAP ...
 39-166 2.16e-54

Synaptic Ras-GTPase activating protein family Pleckstrin homology (PH) domain; The RasSynGAP family is composed of members: DAB2IP, nGAP, and SynGAP. Neuronal growth-associated proteins (nGAPs) are growth cone markers found in multiple types of neurons. There are many nGAPs including Cap1 (Adenylate cyclase-associated protein 1), Capzb (Capping protein (actin filament) muscle Z-line, beta), Clptm1 (Cleft lip and palate associated transmembrane protein 1), Cotl1 (Coactosin-like 1), Crmp1 (Collapsin response mediator protein 1), Cyfip1 (Cytoplasmic FMR1 interacting protein 1), Fabp7 (Fatty acid binding protein 7, brain), Farp2 (FERM, RhoGEF and pleckstrin domain protein 2), Gap43 (Growth associated protein 43), Gnao1 (Guanine nucleotide binding protein (G protein), alpha activating activity polypeptide O), Gnai2 (Guanine nucleotide binding protein (G protein), alpha inhibiting 2), Pacs1 (Phosphofurin acidic cluster sorting protein 1), Rtn1 (Reticulon 1), Sept2 (Septin 2), Snap25 (Synaptosomal-associated protein 25), Strap (Serine/threonine kinase receptor associated protein), Stx7 (Syntaxin 7), and Tmod2 (Tropomodulin 2). SynGAP, a neuronal Ras-GAP, has been shown display both Ras-GAP activity and Ras-related protein (Rap)-GAP activity. Saccharomyces cerevisiae Bud2 and GAP1 members CAPRI (Ca2+-promoted Ras inactivator) and RASAL (Ras-GTPase-activating-like protein) also possess this dual activity. Human DOC-2/DAB2-interacting protein (DAB2IP) is encoded by a tumor suppressor gene and a newly recognized member of the Ras-GTPase-activating family. DAB2IP is a critical component of many signal transduction pathways mediated by Ras and tumor necrosis factors including apoptosis pathways, and it is involved in the formation of many types of tumors. DAB2IP participates in regulation of gene expression and pluripotency of cells. It has been reported that DAB2IP was expressed in different tumor tissues. Little information is available concerning the expression levels of DAB2IP in normal tissues and cells, however, and no studies of its expression patterns during the development of human embryos have been reported. DAB2IP was expressed primarily in cell cytoplasm throughout the fetal development. The expression levels varied among tissues and different gestational ages. 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: 270082  Cd Length: 125  Bit Score: 184.94  E-value: 2.16e-54
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 158261639  39 VPGFFSKRLKGSIKRTKSQSKLDRNTSFRLPSPRSTddRSRGLPKLKESRSHESLLSpcSTVECLDLGRGEPVSVKPLHS 118
Cdd:cd13262    1 ASGFFSRRLKGPLKRTKSVTKLERKSSKRLPRTRLA--RAPAGPRLRGSRSHESLLS--SSSAALDLSADEDVVIRPLHS 76

                         90       100       110       120
                 ....*....|....*....|....*....|....*....|....*...
gi 158261639 119 SILGQDFCFEVTYLSGSKCFSCNSASERDKWMENLRRTVQPNKDNCRR 166
Cdd:cd13262   77 SILGRKHCFQVTTSEGTRCFSCRSAAERDRWIEDLRRAAQPNKDNCRR 124
RasGAP_CLA2_BUD2 cd05137
Ras-GTPase Activating Domain of CLA2/BUD2; CLA2/BUD2 functions as a GTPase-activating protein ...
 295-568 7.58e-53

Ras-GTPase Activating Domain of CLA2/BUD2; CLA2/BUD2 functions as a GTPase-activating protein (GAP) for BUD1/RSR1 and is necessary for proper bud-site selection in yeast. BUD2 has sequence similarity to the catalytic domain of RasGAPs, and stimulates the hydrolysis of BUD1-GTP to BUD1-GDP. Elimination of Bud2p activity by mutation causes a random budding pattern with no growth defect. Overproduction of Bud2p also alters the budding pattern.


Pssm-ID: 213339 [Multi-domain]  Cd Length: 356  Bit Score: 188.93  E-value: 7.58e-53
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 158261639 295 ILPMEQYKESAEF---VTSNYTMLCSVLEPVISVRNkeeLACALVHILQSTGRAKDFLTDLVMSEVD------------- 358
Cdd:cd05137    9 VLPSKNYKPLEELlhnFDLGLTLQIAELVPGDKLER---LSEILLDIFQASGREDEWFMALVEDEIDgidkstsknkdmg 85

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 158261639 359 --RCGEHDvLIFRENTIATKSIEEYLKLVGQQYLHDALGEFIKALYESDENCEVDPSKCSSSELI-------DHQSNLKM 429
Cdd:cd05137   86 ksSNNEAN-LLFRGNSLLTKSLEKYMRRIGKEYLEKSIGDVIRKICEENKDCEVDPSRVKESDSIekeedleENWENLIS 164

                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 158261639 430 CCELAFCKIINSYCVFPRELKEVFaswK--QQCLNRGKQDISERL----ISASLFLRFLCPAIMSPSLFNLMQEYPDDRT 503
Cdd:cd05137  165 LTEEIWNSIYITSNDCPPELRKIL---KhiRAKVEDRYGDFLRTVtlnsVSGFLFLRFFCPAILNPKLFGLLKDHPRPRA 241

                        250       260       270       280       290       300
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 158261639 504 SRTLTLIAKVIQNLANFAKFGNKEEYMAFMNDFLEhewggmkrflleisnpdtiSNTPGFDGYID 568
Cdd:cd05137  242 QRTLTLIAKVLQNLANLTTFGQKEPWMEPMNEFLT-------------------THREELKDYID 287
RasGAP_GAP1_like cd05128
Ras-GTPase Activating Domain of GAP1 and similar proteins; The GAP1 family of Ras ...
 315-554 6.58e-50

Ras-GTPase Activating Domain of GAP1 and similar proteins; The GAP1 family of Ras GTPase-activating proteins includes GAP1(m) (or RASA2), GAP1_IP4BP (or RASA3), Ca2+ -promoted Ras inactivator (CAPRI, or RASAL4), and Ras GTPase activating-like proteins (RASAL) or RASAL1. The members are characterized by a conserved domain structure comprising N-terminal tandem C2 domains, a highly conserved central RasGAP domain, and a C-terminal pleckstrin homology domain that is associated with a Bruton's tyrosine kinase motif. While this domain structure is conserved, a small change in the function of each individual domain and the interaction between domains has a marked effect on the regulation of each protein.


Pssm-ID: 213330  Cd Length: 269  Bit Score: 177.44  E-value: 6.58e-50
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 158261639 315 LCSVLEPVISVrNKEELACALVHILQSTGRAKDFLTDLVMSEVDRCGehDV-LIFRENTIATKSIEEYLKLVGQQYLHDA 393
Cdd:cd05128   23 AVYLLEELVKV-DKDDVARPLVRIFLHHGQIVPLLRALASREISKTQ--DPnTLFRGNSLASKCMDEFMKLVGMQYLHET 99

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 158261639 394 LGEFIKALYESDENCEVDPSKCSSSELID-HQSNLKMCCELAFCKIINSYCVFPRELKEVFASWKQQCLNR--GKQDISE 470
Cdd:cd05128  100 LKPVIDEIFSEKKSCEIDPSKLKDGEVLEtNLANLRGYVERVFKAITSSARRCPTLMCEIFSDLRESAAQRfpDNEDVPY 179

                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 158261639 471 RLISASLFLRFLCPAIMSPSLFNLMQEYPDDRTSRTLTLIAKVIQNLANF----AKFGNKEEYMA-FMNDFL-EHEWGGM 544
Cdd:cd05128  180 TAVSGFIFLRFFAPAILNPKLFGLREEHPDPQTARTLTLISKTIQTLGNLgsssSGLGVKEAYMSpLYERFTdEQHVDAV 259

                        250
                 ....*....|
gi 158261639 545 KRFLLEISNP 554
Cdd:cd05128  260 KKFLDRISSV 269
RasGAP_p120GAP cd05391
Ras-GTPase Activating Domain of p120; p120GAP is a negative regulator of Ras that stimulates ...
 295-579 9.47e-43

Ras-GTPase Activating Domain of p120; p120GAP is a negative regulator of Ras that stimulates hydrolysis of bound GTP to GDP. Once the Ras regulator p120GAP, a member of the GAP protein family, is recruited to the membrane, it is transiently immobilized to interact with Ras-GTP. The down-regulation of Ras by p120GAP is a critical step in the regulation of many cellular processes, which is disrupted in approximately 30% of human cancers. p120GAP contains SH2, SH3, PH, calcium- and lipid-binding domains, suggesting its involvement in a complex network of cellular interactions in vivo.


Pssm-ID: 213340  Cd Length: 328  Bit Score: 159.19  E-value: 9.47e-43
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 158261639 295 ILPMEQYKESAEFVTSNYTMLCSVLEPVISvRNKEELACALVHILQSTGRAKDFLTDLVMSEVDRCGEHDVLiFRENTIA 374
Cdd:cd05391    4 IMPEEEYSELKELILQKELHVVYALAHVCG-QDRTLLASILLRIFRHEKLESLLLRTLNDREISMEDEATTL-FRATTLA 81

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 158261639 375 TKSIEEYLKLVGQQYLHDALGEFIKALYESDENCEVDPSKCSSSEliDHQSNLKMCCELAFC---KIINSYCVFPRELKE 451
Cdd:cd05391   82 STLMEQYMKATATPFVHHALKDTILKILESKQSCELNPSKLEKNE--DVNTNLEHLLNILSElveKIFMAAEILPPTLRY 159

                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 158261639 452 VFaSWKQQCLNR---GKQDISERLISASLFLRFLCPAIMSPSLFNLMQEYPDDRTSRTLTLIAKVIQNLANFAKFGNKEE 528
Cdd:cd05391  160 IY-GCLQKSVQQkwpTNTTVRTRVVSGFVFLRLICPAILNPRMFNIISETPSPTAARTLTLVAKSLQNLANLVEFGAKEP 238

                        250       260       270       280       290
                 ....*....|....*....|....*....|....*....|....*....|..
gi 158261639 529 YMAFMNDFLEHEWGGMKRFLLEISN-PDTISNTPGFDGyiDLGRELSVLHSL 579
Cdd:cd05391  239 YMEGVNPFIKKNKERMIMFLDELGNvPELPDTTEHSRT--DLSRDLAALHEI 288
RasGAP_Neurofibromin_like cd05392
Ras-GTPase Activating Domain of proteins similar to neurofibromin; Neurofibromin-like proteins ...
 297-580 1.36e-42

Ras-GTPase Activating Domain of proteins similar to neurofibromin; Neurofibromin-like proteins include the Saccharomyces cerevisiae RasGAP proteins Ira1 and Ira2, the closest homolog of neurofibromin, which is responsible for the human autosomal dominant disease neurofibromatosis type I (NF1). The RasGAP Ira1/2 proteins are negative regulators of the Ras-cAMP signaling pathway and conserved from yeast to human. In yeast Ras proteins are activated by GEFs, and inhibited by two GAPs, Ira1 and Ira2. Ras proteins activate the cAMP/protein kinase A (PKA) pathway, which controls metabolism, stress resistance, growth, and meiosis. Recent studies showed that the kelch proteins Gpb1 and Gpb2 inhibit Ras activity via association with Ira1 and Ira2. Gpb1/2 bind to a conserved C-terminal domain of Ira1/2, and loss of Gpb1/2 results in a destabilization of Ira1 and Ira2, leading to elevated levels of Ras2-GTP and uninhibited cAMP-PKA signaling. Since the Gpb1/2 binding domain on Ira1/2 is conserved in the human neurofibromin protein, the studies suggest that an analogous signaling mechanism may contribute to the neoplastic development of NF1.


Pssm-ID: 213341  Cd Length: 317  Bit Score: 158.22  E-value: 1.36e-42
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 158261639 297 PMEQYKESAEFVTSNYTMLCSVLEpVISVRNKEELACALVHILQSTGRAKDFLTDLVMSEVDRCgEHDVLIFRENTIATK 376
Cdd:cd05392    2 KSEAYDELLELLIEDPQLLLAIAE-VCPSSEVDLLAQSLLNLFETRNRLLPLISWLIEDEISHT-SRAADLFRRNSVATR 79

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 158261639 377 SIEEYLKLVGQQYLHDALGEFIKALYESDENCEVDPSKCSSSELIDHQSNLKMCCELAFCKIINSYCVFPRELKEVFASW 456
Cdd:cd05392   80 LLTLYAKSVGNKYLRKVLRPLLTEIVDNKDYFEVEKIKPDDENLEENADLLMKYAQMLLDSITDSVDQLPPSFRYICNTI 159

                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 158261639 457 KQQCLNRGKqDISERLISASLFLRFLCPAIMSPSLFNLMQEYPDDRTSRTLTLIAKVIQNLANFAKFGNKEEYMAFMNDF 536
Cdd:cd05392  160 YESVSKKFP-DAALIAVGGFLFLRFICPAIVSPESENLLDPPPTPEARRSLILIAKVLQNIANGVLFSLKEPYLESLNEF 238

                        250       260       270       280
                 ....*....|....*....|....*....|....*....|....
gi 158261639 537 LEHEWGGMKRFLLEISNPDTISNTPGFDGYIDLGRELSVLHSLL 580
Cdd:cd05392  239 LKKNSDRIQQFLSEVSTIPPTDPIFDESDEEPITADLRYLHKFL 282
RasGAP_RASA3 cd05134
Ras-GTPase Activating Domain of RASA3; RASA3 (or GAP1_IP4BP) is a member of the GAP1 family ...
 326-553 1.18e-38

Ras-GTPase Activating Domain of RASA3; RASA3 (or GAP1_IP4BP) is a member of the GAP1 family and has been shown to specifically bind 1,3,4,5-tetrakisphosphate (IP4). Thus, RASA3 may function as an IP4 receptor. The members of GAP1 family are characterized by a conserved domain structure comprising N-terminal tandem C2 domains, a highly conserved central RasGAP domain, and a C-terminal pleckstrin-homology domain that is associated with a Bruton's tyrosine kinase motif. Purified RASA3 stimulates GAP activity on Ras with about a five-fold lower potency than p120RasGAP, but shows no GAP-stimulating activity at all against Rac or Rab3A.


Pssm-ID: 213336  Cd Length: 269  Bit Score: 145.17  E-value: 1.18e-38
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 158261639 326 RNKEELACALVHILQSTGRAKDFLTDLVMSEVDRCGEHDVlIFRENTIATKSIEEYLKLVGQQYLHDALGEFIKALYESD 405
Cdd:cd05134   33 REKQEAAIPLVRLFLHYGKIVPFISAIASAEVNRTQDPNT-IFRGNSLTSKCIDETMKLAGMHYLQVTLKPIIDEICQEH 111

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 158261639 406 ENCEVDPSKCSSSE-LIDHQSNLKMCCELAFCKIINSYCVFPRELKEVFASWKQQCLNR--GKQDISERLISASLFLRFL 482
Cdd:cd05134  112 KPCEIDPVKLKDGEnLENNRENLRQYVDRIFRVITKSGVSCPTVMCDIFFSLRESAAKRfqVDPDVRYTAVSSFIFLRFF 191

                        170       180       190       200       210       220       230
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 158261639 483 CPAIMSPSLFNLMQEYPDDRTSRTLTLIAKVIQNLANFAKFGN---KEEYMA-FMNDFLEHEWG-GMKRFLLEISN 553
Cdd:cd05134  192 APAILSPNLFQLTPHHPDPQTSRTLTLISKTIQTLGSLSKSKSanfKESYMAaFYDYFNEQKYAdAVKNFLDLISS 267
RasGAP_RASAL cd05135
Ras-GTPase Activating Domain of RASAL1 and similar proteins; Ras GTPase activating-like ...
 290-548 2.71e-33

Ras-GTPase Activating Domain of RASAL1 and similar proteins; Ras GTPase activating-like protein (RASAL) or RASAL1 is a member of the GAP1 family, and a Ca2+ sensor responding in-phase to repetitive Ca2+ signals by associating with the plasma membrane and deactivating Ras. It contains a conserved domain structure comprising N-terminal tandem C2 domains, a highly conserved central RasGAP domain, and a C-terminal pleckstrin-homology domain that is associated with a Bruton's tyrosine kinase motif. RASAL, like Ca2+ -promoted Ras inactivator (CAPRI, or RASAL4), is a cytosolic protein that undergoes a rapid translocation to the plasma membrane in response to receptor-mediated elevation in the concentration of intracellular free Ca2+, a translocation that activates its ability to function as a RasGAP. However, unlike RASAL4, RASAL undergoes an oscillatory translocation to the plasma membrane that occurs in synchrony with repetitive Ca2+ spikes.


Pssm-ID: 213337  Cd Length: 287  Bit Score: 130.32  E-value: 2.71e-33
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 158261639 290 FQTITILPMEQYKESAEFVTSNytmLCSVLEPVISVRNKEELACALVHILQSTGRAKDFLTDLVMSEVDRCGEHDVLiFR 369
Cdd:cd05135    5 YQPLIDLLVESVQSPAEAEDST---PLAMLEEVTTGESRQDVATKLVKIFLGQGLVVPFLDYLNTREVGRTTDPNTL-FR 80

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 158261639 370 ENTIATKSIEEYLKLVGQQYLHDALGEFIKALYESDENCEVDPSK--------------CSSSELIDH-----QSNLKMC 430
Cdd:cd05135   81 SNSLASKSMEQFMKVVGMPYLHEVLKPVINRIFEEKKYVELDPCKidlnrtrrisfkgsLSEAQVRESslellQGYLGSI 160

                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 158261639 431 CElafcKIINSYCVFPRELKEVFASWKQQCLNR----GKQDISERLISASLFLRFLCPAIMSPSLFNLMQEYPDDRTSRT 506
Cdd:cd05135  161 ID----AIVGSVDQCPPVMRVAFKQLHKRVEERfpeaEHQDVKYLAISGFLFLRFFAPAILTPKLFQLREQHADPRTSRT 236

                        250       260       270       280
                 ....*....|....*....|....*....|....*....|....
gi 158261639 507 LTLIAKVIQNLANF-AKFGN-KEEYMAFMNDFLEHEWGGMKRFL 548
Cdd:cd05135  237 LLLLAKAVQSIGNLgLQLGQgKEQWMAPLHPFILQSVARVKDFL 280
RasGAP_Neurofibromin cd05130
Ras-GTPase Activating Domain of neurofibromin; Neurofibromin is the product of the ...
 322-582 1.03e-32

Ras-GTPase Activating Domain of neurofibromin; Neurofibromin is the product of the neurofibromatosis type 1 gene (NF1) and shares a region of similarity with catalytic domain of the mammalian p120RasGAP protein and an extended similarity with the Saccharomyces cerevisiae RasGAP proteins Ira1 and Ira2. Neurofibromin has been shown to function as a GAP (GTPase-activating protein) which inhibits low molecular weight G proteins such as Ras by stimulating their intrinsic GTPase activity. NF1 is a common genetic disorder characterized by various symptoms ranging from predisposition for the development of tumors to learning disability or mental retardation. Loss of neurofibromin activity can be correlated to the increase in Ras-GTP concentration in neurofibromas of NF1 of patients, supporting the notion that unregulated Ras signaling may contribute to their development.


Pssm-ID: 213332 [Multi-domain]  Cd Length: 332  Bit Score: 129.75  E-value: 1.03e-32
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 158261639 322 VISVRNKEELACALVHILQSTGRAKDFLTDLVMSEVDRCGEHDVLiFRENTIATKSIEEYLKLVGQQYLHDALGEFIKAL 401
Cdd:cd05130   33 VVPCSQMDELARVLVTLFDSKHLLYQLLWNMFSKEVELADSMQTL-FRGNSLASKIMTFCFKVYGATYLQSLLEPLLRTM 111

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 158261639 402 YESDE--NCEVDPSKCSSSELI-DHQSNLKMCCELAFCKIINSYCVFPRELKEVFaswkqQCLNrgkQDISERL------ 472
Cdd:cd05130  112 ITSSEwvSYEVDPTRLEGNENLeENQRNLLQLTEKFFHAIISSSDEFPPQLRSVC-----HCLY---QVVSHRFpnsglg 183

                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 158261639 473 -ISASLFLRFLCPAIMSPSLFNLMQEYPDDRTSRTLTLIAKVIQNLANFAKFgNKEEYMAFMNDFLEHEWGGMKRFLLEI 551
Cdd:cd05130  184 aVGSAIFLRFINPAIVSPYEYGILDREPPPRVKRGLKLMSKILQNIANHVLF-TKEAHMLPFNDFLRNHFEAGRRFFSSI 262

                        250       260       270
                 ....*....|....*....|....*....|...
gi 158261639 552 SNPDTISNTPGFDG--YIDLGRELSvLHSLLWE 582
Cdd:cd05130  263 ASDCGAVDGPSSKYlsFINDANVLA-LHRLLWN 294
PH_RASAL3 cd13374
RAS protein activator like-3 Pleckstrin homology (PH) domain; RASAL3 is thought to be a Ras ...
 9-181 1.29e-30

RAS protein activator like-3 Pleckstrin homology (PH) domain; RASAL3 is thought to be a Ras GTPase-activating protein. It is involved in positive regulation of Ras GTPase activity and of small GTPase mediated signal transduction as well as negative regulation of Ras protein signal transduction. It contains a PH domain, a C2 domain, and a Ras-GAP 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: 270177  Cd Length: 146  Bit Score: 117.81  E-value: 1.29e-30
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 158261639   9 ERSPRRRSISGTSTSEKPNsmdtantspfkvpgffskrLKGSIKRTKSQSKldrntsfrlPSPRSTDDRSRGLPKLKESR 88
Cdd:cd13374    3 DREPGKTEPEAAGPNQGHN-------------------VRGLLKRLKEKKK---------AKAESTGTGRDGPPSALGSR 54

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 158261639  89 SHESLLSPcstvecLDLGRGEPVSVKPLHSSILGQDFCFEVTYLSGSKCFSCNSASERDKWMENLRRTVQPNKDNCRRAE 168
Cdd:cd13374   55 ESLATISE------LDLGAERDVRVWPLHPSLLGEPHCFQVTWPGGSRCFSCRSAAERDRWIEDLRRSFQPHQDNVEREE 128

                        170
                 ....*....|...
gi 158261639 169 NVLRLWIIEAKDL 181
Cdd:cd13374  129 TWLSVWVHEAKGL 141
RasGAP pfam00616
GTPase-activator protein for Ras-like GTPase; All alpha-helical domain that accelerates the ...
 348-519 8.82e-30

GTPase-activator protein for Ras-like GTPase; All alpha-helical domain that accelerates the GTPase activity of Ras, thereby "switching" it into an "off" position.


Pssm-ID: 459871  Cd Length: 207  Bit Score: 117.39  E-value: 8.82e-30
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 158261639  348 FLTDLVMSEVDRCGEhDVLIFRENTIATKSIEEYLKL-VGQQYLHDALGEFIKALYESDE-NCEVDPSKC---------- 415
Cdd:pfam00616   1 LISELIEEEIESSDN-PNDLLRGNSLVSKLLETYNRRpRGQEYLKKVLGPLVRKIIEDEDlDLESDPRKIyeslinqeel 79

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 158261639  416 ---------------------SSSELIDHQSNLKMCCELAFCKIINSYCVFPREL----KEVFASWKQQCLNRGKQDISE 470
Cdd:pfam00616  80 ktgrsdlprdvspeeaiedpeVRQIFEDNLQKLRELADEFLDAIYSSLNQLPYGIryicKQLYELLEEKFPDASEEEILN 159

                         170       180       190       200
                  ....*....|....*....|....*....|....*....|....*....
gi 158261639  471 rLISASLFLRFLCPAIMSPSLFNLMQEYPDDRTSRTLTLIAKVIQNLAN 519
Cdd:pfam00616 160 -AIGGFLFLRFFCPAIVNPDLFGLVDHQISPKQRRNLTLIAKVLQNLAN 207
RasGAP_RASA4 cd05395
Ras-GTPase Activating Domain of RASA4; Ras GTPase activating-like 4 protein (RASAL4), also ...
 315-553 9.27e-30

Ras-GTPase Activating Domain of RASA4; Ras GTPase activating-like 4 protein (RASAL4), also known as Ca2+ -promoted Ras inactivator (CAPRI), is a member of the GAP1 family. Members of the GAP1 family are characterized by a conserved domain structure comprising N-terminal tandem C2 domains, a highly conserved central RasGAP domain, and a C-terminal pleckstrin-homology domain that is associated with a Bruton's tyrosine kinase motif. RASAL4, like RASAL, is a cytosolic protein that undergoes a rapid translocation to the plasma membrane in response to a receptor-mediated elevation in the concentration of intracellular free Ca2+ ([Ca2+]i). However, unlike RASAL, RASAL4 does not sense oscillations in [Ca2+]i.


Pssm-ID: 213343 [Multi-domain]  Cd Length: 287  Bit Score: 119.98  E-value: 9.27e-30
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 158261639 315 LCSVLEPVISVRNKEELACALVHILQSTGRAKDFLTDLVMSEVDRCGEHDVLiFRENTIATKSIEEYLKLVGQQYLHDAL 394
Cdd:cd05395   27 LISLIDETTTAECRQEVATNLVKLFLGQGLAKEFLDLLFQLELDKTTEPNTL-FRSNSLASKSMESFLKVAGMQYLHSVL 105

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 158261639 395 GEFIKALYESDENCEVDPSK-------CS-------SSELIDHQSN-LKMCCELAFCKIINSYCVFPRELKEVFASWKQQ 459
Cdd:cd05395  106 GPTINRVFEEKKYVELDPSKveikdvgCSglhriqtESEVIEQSAQlLQSYLGELLSAISKSVKYCPAVIRATFRQLFKR 185

                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 158261639 460 CLNR--GKQDISERLISASLFL--RFLCPAIMSPSLFNLMQEYPDDRTSRTLTLIAKVIQNLANFAKFGN--KEEYMAFM 533
Cdd:cd05395  186 VQERfpENQHQNVKFIAVTSFLclRFFSPAIMSPKLFHLREKHADARTSRTLLLLAKAVQNVGNMDTLASraKEAWMAPL 265

                        250       260
                 ....*....|....*....|
gi 158261639 534 NDFLEHEWGGMKRFLLEISN 553
Cdd:cd05395  266 QPAIQQGVAQLKDFITKLVD 285
RasGAP_RASA2 cd05394
Ras-GTPase Activating Domain of RASA2; RASA2 (or GAP1(m)) is a member of the GAP1 family of ...
 326-553 9.26e-28

Ras-GTPase Activating Domain of RASA2; RASA2 (or GAP1(m)) is a member of the GAP1 family of Ras GTPase-activating proteins that includes GAP1_IP4BP (or RASA3), CAPRI, and RASAL. In vitro, RASA2 has been shown to bind inositol 1,3,4,5-tetrakisphosphate (IP4), the water soluble inositol head group of the lipid second messenger phosphatidylinositol 3,4,5-trisphosphate (PIP3). In vivo studies also demonstrated that RASA2 binds PIP3, and it is recruited to the plasma membrane following agonist stimulation of PI 3-kinase. Furthermore, the membrane translocation is a consequence of the ability of its pleckstrin homology (PH) domain to bind PIP3.


Pssm-ID: 213342  Cd Length: 272  Bit Score: 113.84  E-value: 9.26e-28
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 158261639 326 RNKEELACALVHILQSTGRAKDFLTDLVMSEVDRCGEHDVlIFRENTIATKSIEEYLKLVGQQYLHDALGEFIKALYESD 405
Cdd:cd05394   33 RDKYDAVLPLVRLLLHHNKLVPFVAAVAALDLKDTQEANT-IFRGNSLATRCLDEMMKIVGKHYLKVTLKPVLDEICESP 111

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 158261639 406 ENCEVDPSKCSSSELID-HQSNLKMCCELAFCKIINSYCVFPRELKEVFASWKQQCLNRGKQD--ISERLISASLFLRFL 482
Cdd:cd05394  112 KPCEIDPIKLKEGDNVEnNKENLRYYVDKVFFSIVKSSMSCPTLMCDVFRSLRHLAVKRFPNDphVQYSAVSSFVFLRFF 191

                        170       180       190       200       210       220       230
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 158261639 483 CPAIMSPSLFNLMQEYPDDRTSRTLTLIAKVIQNLANFAKFGN------KEEYMA-FMNDFLEHEW-GGMKRFLLEISN 553
Cdd:cd05394  192 AVAVVSPHTFQLRPHHPDAQTSRTLTLISKTIQTLGSWGSLSKsklssfKETFMCdFFKMFQEEKYiEKVKKFLDEISS 270
RasGAP_GAPA cd05132
Ras-GTPase Activating Domain of GAPA; GAPA is an IQGAP-related protein and is predicted to ...
 369-606 1.75e-25

Ras-GTPase Activating Domain of GAPA; GAPA is an IQGAP-related protein and is predicted to bind to small GTPases, which are yet to be identified. IQGAP proteins are integral components of cytoskeletal regulation. Results from truncated GAPAs indicated that almost the entire region of GAPA homologous to IQGAP is required for cytokinesis in Dictyostelium. More members of the IQGAP family are emerging, and evidence suggests that there are both similarities and differences in their function.


Pssm-ID: 213334  Cd Length: 352  Bit Score: 108.98  E-value: 1.75e-25
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 158261639 369 RENTIATKSIEEYLKLV-GQQYLHDALGEFIKALYE-SDENCEVDPSK---------------------------CSSSE 419
Cdd:cd05132   49 RANTAVSRMMTTYTRRGpGQSYLKTVLADRINDLISlKDLNLEINPLKvyeqmindieldtglpsnlprgitpeeAAENP 128

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 158261639 420 LIDH--QSNLKMCCELA---FCKIINSYCVFP----------REL-KEVF--ASWKQQClnrgkqdiseRLISASLFLRF 481
Cdd:cd05132  129 AVQNiiEPRLEMLEEITnsfLEAIINSLDEVPygirwickqiRSLtRRKFpdASDETIC----------SLIGGFFLLRF 198

                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 158261639 482 LCPAIMSPSLFNLMQEYPDDRTSRTLTLIAKVIQNLANFAKFGnKEEYMAFMNDFLEHEWGGMKRFLLEISNPDTISNTP 561
Cdd:cd05132  199 INPAIVSPQAYMLVDGKPSDNTRRTLTLIAKLLQNLANKPSYS-KEPYMAPLQPFVEENKERLNKFLNDLCEVDDFYESL 277

                        250       260       270       280       290
                 ....*....|....*....|....*....|....*....|....*....|....*
gi 158261639 562 GFDGYIDLGR----------ELSVLHSLLWEVVSQLDKGENSFLQATVAKLGPLP 606
Cdd:cd05132  278 ELDQYIALSKkdlsinitlnEIYNTHSLLVKHLAELAPDHNDHLRLILQELGPAP 332
C2 cd00030
C2 domain; The C2 domain was first identified in PKC. C2 domains fold into an 8-standed ...
 171-268 6.19e-11

C2 domain; The C2 domain was first identified in PKC. C2 domains fold into an 8-standed beta-sandwich that can adopt 2 structural arrangements: Type I and Type II, distinguished by a circular permutation involving their N- and C-terminal beta strands. Many C2 domains are Ca2+-dependent membrane-targeting modules that bind a wide variety of substances including bind phospholipids, inositol polyphosphates, and intracellular proteins. Most C2 domain proteins are either signal transduction enzymes that contain a single C2 domain, such as protein kinase C, or membrane trafficking proteins which contain at least two C2 domains, such as synaptotagmin 1. However, there are a few exceptions to this including RIM isoforms and some splice variants of piccolo/aczonin and intersectin which only have a single C2 domain. C2 domains with a calcium binding region have negatively charged residues, primarily aspartates, that serve as ligands for calcium ions.


Pssm-ID: 175973 [Multi-domain]  Cd Length: 102  Bit Score: 60.16  E-value: 6.19e-11
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 158261639 171 LRLWIIEAKDLAPKKK-----YFCELCLDDTLFARTTSKTKADNIFWGEHFEF-FSLPPLHSITVHIYkDVEKRKKKDkn 244
Cdd:cd00030    1 LRVTVIEARNLPAKDLngksdPYVKVSLGGKQKFKTKVVKNTLNPVWNETFEFpVLDPESDTLTVEVW-DKDRFSKDD-- 77

                         90       100
                 ....*....|....*....|....*
gi 158261639 245 nYVGLVNIPTASVTGR-QFVEKWYP 268
Cdd:cd00030   78 -FLGEVEIPLSELLDSgKEGELWLP 101
C2_Ras_p21A1 cd08400
C2 domain present in RAS p21 protein activator 1 (RasA1); RasA1 is a GAP1 (GTPase activating ...
 171-290 1.74e-10

C2 domain present in RAS p21 protein activator 1 (RasA1); RasA1 is a GAP1 (GTPase activating protein 1), a Ras-specific GAP member, which suppresses Ras function by enhancing the GTPase activity of Ras proteins resulting in the inactive GDP-bound form of Ras. In this way it can control cellular proliferation and differentiation. RasA1 contains a C2 domain, a Ras-GAP domain, a pleckstrin homology (PH)-like domain, a SH3 domain, and 2 SH2 domains. C2 domains fold into an 8-standed beta-sandwich that can adopt 2 structural arrangements: Type I and Type II, distinguished by a circular permutation involving their N- and C-terminal beta strands. Many C2 domains are Ca2+-dependent membrane-targeting modules that bind a wide variety of substances including bind phospholipids, inositol polyphosphates, and intracellular proteins. Most C2 domain proteins are either signal transduction enzymes that contain a single C2 domain, such as protein kinase C, or membrane trafficking proteins which contain at least two C2 domains, such as synaptotagmin 1. However, there are a few exceptions to this including RIM isoforms and some splice variants of piccolo/aczonin and intersectin which only have a single C2 domain. C2 domains with a calcium binding region have negatively charged residues, primarily aspartates, that serve as ligands for calcium ions. Members here have a type-I topology.


Pssm-ID: 176045 [Multi-domain]  Cd Length: 126  Bit Score: 59.69  E-value: 1.74e-10
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 158261639 171 LRLWIIEAKDLAPKK--KYFCELCLDDTLFARTTSKTkADNIFWGEHFEFFSLPP-LHSITVHIYKdvekRKKKDKNNYV 247
Cdd:cd08400    6 LQLNVLEAHKLPVKHvpHPYCVISLNEVKVARTKVRE-GPNPVWSEEFVFDDLPPdVNSFTISLSN----KAKRSKDSEI 80

                         90       100       110       120
                 ....*....|....*....|....*....|....*....|...
gi 158261639 248 GLVNIPTASVTGRQFVEKWYPVSTPTPNKGKTGGpSIRIKSRF 290
Cdd:cd08400   81 AEVTVQLSKLQNGQETDEWYPLSSASPLKGGEWG-SLRIRARY 122
C2A_RasGAP cd08383
C2 domain (first repeat) of Ras GTPase activating proteins (GAPs); RasGAPs suppress Ras ...
 171-290 5.58e-10

C2 domain (first repeat) of Ras GTPase activating proteins (GAPs); RasGAPs suppress Ras function by enhancing the GTPase activity of Ras proteins resulting in the inactive GDP-bound form of Ras. In this way it can control cellular proliferation and differentiation. The proteins here all contain either a single C2 domain or two tandem C2 domains, a Ras-GAP domain, and a pleckstrin homology (PH)-like domain. C2 domains fold into an 8-standed beta-sandwich that can adopt 2 structural arrangements: Type I and Type II, distinguished by a circular permutation involving their N- and C-terminal beta strands. Many C2 domains are Ca2+-dependent membrane-targeting modules that bind a wide variety of substances including bind phospholipids, inositol polyphosphates, and intracellular proteins. Most C2 domain proteins are either signal transduction enzymes that contain a single C2 domain, such as protein kinase C, or membrane trafficking proteins which contain at least two C2 domains, such as synaptotagmin 1. However, there are a few exceptions to this including RIM isoforms and some splice variants of piccolo/aczonin and intersectin which only have a single C2 domain. C2 domains with a calcium binding region have negatively charged residues, primarily aspartates, that serve as ligands for calcium ions. Members here have a type-I topology.


Pssm-ID: 176029 [Multi-domain]  Cd Length: 117  Bit Score: 57.66  E-value: 5.58e-10
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 158261639 171 LRLWIIEAKDLAPKK--KYFCELCLDDTLFARTTSKTKAdNIFWGEHFEFFSLPPL---HSITVHIYKdvEKRKKKDknn 245
Cdd:cd08383    2 LRLRILEAKNLPSKGtrDPYCTVSLDQVEVARTKTVEKL-NPFWGEEFVFDDPPPDvtfFTLSFYNKD--KRSKDRD--- 75

                         90       100       110       120
                 ....*....|....*....|....*....|....*....|....*
gi 158261639 246 yVGLVNIPTASVTGRQFVEKWYPVSTPTPNKGKTGgpSIRIKSRF 290
Cdd:cd08383   76 -IVIGKVALSKLDLGQGKDEWFPLTPVDPDSEVQG--SVRLRARY 117
C2 pfam00168
C2 domain;
169-269 8.39e-10

C2 domain;


Pssm-ID: 425499 [Multi-domain]  Cd Length: 104  Bit Score: 56.94  E-value: 8.39e-10
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 158261639  169 NVLRLWIIEAKDLAPKKKY-----FCELCL-DDTLFARTTSKTKADNIFWGEHFEfFSLPPLHSITVHIYkdVEKRKKKD 242
Cdd:pfam00168   1 GRLTVTVIEAKNLPPKDGNgtsdpYVKVYLlDGKQKKKTKVVKNTLNPVWNETFT-FSVPDPENAVLEIE--VYDYDRFG 77

                          90       100
                  ....*....|....*....|....*..
gi 158261639  243 KNNYVGLVNIPTASVTGRQFVEKWYPV 269
Cdd:pfam00168  78 RDDFIGEVRIPLSELDSGEGLDGWYPL 104
C2 smart00239
Protein kinase C conserved region 2 (CalB); Ca2+-binding motif present in phospholipases, ...
 170-266 7.08e-09

Protein kinase C conserved region 2 (CalB); Ca2+-binding motif present in phospholipases, protein kinases C, and synaptotagmins (among others). Some do not appear to contain Ca2+-binding sites. Particular C2s appear to bind phospholipids, inositol polyphosphates, and intracellular proteins. Unusual occurrence in perforin. Synaptotagmin and PLC C2s are permuted in sequence with respect to N- and C-terminal beta strands. SMART detects C2 domains using one or both of two profiles.


Pssm-ID: 214577 [Multi-domain]  Cd Length: 101  Bit Score: 54.03  E-value: 7.08e-09
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 158261639   170 VLRLWIIEAKDLAPKKKY-----FCELCLD--DTLFARTTSKTKADNIFWGEHFEFFSLPP-LHSITVHIYKDvekrKKK 241
Cdd:smart00239   1 TLTVKIISARNLPPKDKGgksdpYVKVSLDgdPKEKKKTKVVKNTLNPVWNETFEFEVPPPeLAELEIEVYDK----DRF 76

                           90       100
                   ....*....|....*....|....*
gi 158261639   242 DKNNYVGLVNIPTASVTGRQFVEKW 266
Cdd:smart00239  77 GRDDFIGQVTIPLSDLLLGGRHEKL 101
RasGAP_IQGAP2 cd05131
Ras-GTPase Activating Domain of IQ motif containing GTPase activating protein 2; IQGAP2 is a ...
 373-608 5.93e-08

Ras-GTPase Activating Domain of IQ motif containing GTPase activating protein 2; IQGAP2 is a member of the IQGAP family that contains a calponin-homology (CH) domain which binds F-actin, IQGAP-specific repeat, a single WW domain, four IQ motifs which mediate interactions with calmodulin, and a Ras-GTPase-activating protein (GAP)-related domain that binds Rho family GTPases. IQGAP2 and IQGAP3 play important roles in the regulation of the cytoskeleton for axon outgrowth in hippocampal neurons and are thought to stay in a common regulatory pathway. The results of RNA interference studies indicated that IQGAP3 partially compensates functions of IQGAP2, but has lesser ability than IQGAP2 to promote axon outgrowth in hippocampal neuron. Moreover, IQGAP2 is required for the cadherin-mediated cell-to-cell adhesion in Xenopus laevis embryos.


Pssm-ID: 213333 [Multi-domain]  Cd Length: 359  Bit Score: 55.77  E-value: 5.93e-08
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 158261639 373 IATKSIEEYLKLVGQqyLHDALGEFIKALYE-SDENCEVDP---SKCSSSelidhQSNLKMCCELAFCKIINSYCVFPRE 448
Cdd:cd05131   85 INTNPVEVYKAWVNQ--LETATGEASKLPYDvTTEQALTHPevvNKLESS-----IQSLRSVTDKVLGSIFSSLDLIPYG 157

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 158261639 449 LKEVfASWKQQCLNRGKQDISE----RLISASLFLRFLCPAIMSPSLFNLM------QEYPDDRtsRTLTLIAKVIQNLA 518
Cdd:cd05131  158 MRYI-AKVLKNSLHEKFPDATEdellKIVGNLLYYRYMNPAIVAPDGFDIIdmtaggQIHSEQR--RNLGSVAKVLQHAA 234

                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 158261639 519 NFAKFGNKEEYMAFMNDFLEHEWGGMKRFL---LEISNPDTISNTPGFDGYIDLGR--------ELSVLHSLLWEVVSQL 587
Cdd:cd05131  235 SNKLFEGENAHLSSMNSYLSQTYQKFRKFFqaaCDVPEPEEKFNIDEYSDMVTLSKpviyisieEIINTHSLLLEHQDAI 314

                        250       260
                 ....*....|....*....|.
gi 158261639 588 DKGENSFLQATVAKLGPLPRV 608
Cdd:cd05131  315 APDQNDLLHELLKDLGEVPDV 335
C2A_C2C_Synaptotagmin_like cd08391
C2 domain first and third repeat in Synaptotagmin-like proteins; Synaptotagmin is a ...
 170-268 8.90e-08

C2 domain first and third repeat in Synaptotagmin-like proteins; Synaptotagmin is a membrane-trafficking protein characterized by a N-terminal transmembrane region, a linker, and 2 C-terminal C2 domains. Previously all synaptotagmins were thought to be calcium sensors in the regulation of neurotransmitter release and hormone secretion, but it has been shown that not all of them bind calcium. Of the 17 identified synaptotagmins only 8 bind calcium (1-3, 5-7, 9, 10). The function of the two C2 domains that bind calcium are: regulating the fusion step of synaptic vesicle exocytosis (C2A) and binding to phosphatidyl-inositol-3,4,5-triphosphate (PIP3) in the absence of calcium ions and to phosphatidylinositol bisphosphate (PIP2) in their presence (C2B). C2B also regulates also the recycling step of synaptic vesicles. C2 domains fold into an 8-standed beta-sandwich that can adopt 2 structural arrangements: Type I and Type II, distinguished by a circular permutation involving their N- and C-terminal beta strands. Many C2 domains are Ca2+-dependent membrane-targeting modules that bind a wide variety of substances including bind phospholipids, inositol polyphosphates, and intracellular proteins. Most C2 domain proteins are either signal transduction enzymes that contain a single C2 domain, such as protein kinase C, or membrane trafficking proteins which contain at least two C2 domains, such as synaptotagmin 1. However, there are a few exceptions to this including RIM isoforms and some splice variants of piccolo/aczonin and intersectin which only have a single C2 domain. C2 domains with a calcium binding region have negatively charged residues, primarily aspartates, that serve as ligands for calcium ions. This cd contains either the first or third repeat in Synaptotagmin-like proteins with a type-I topology.


Pssm-ID: 176037 [Multi-domain]  Cd Length: 121  Bit Score: 51.52  E-value: 8.90e-08
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 158261639 170 VLRLWIIEAKDLAPKKKYF-----------CELCLDDTLFartTSKTKADNI--FWGEHFEFFsLPPLH--SITVHIY-K 233
Cdd:cd08391    2 VLRIHVIEAQDLVAKDKFVgglvkgksdpyVIVRVGAQTF---KSKVIKENLnpKWNEVYEAV-VDEVPgqELEIELFdE 77

                         90       100       110
                 ....*....|....*....|....*....|....*
gi 158261639 234 DVekrkkkDKNNYVGLVNIPTASVTGRQFVEKWYP 268
Cdd:cd08391   78 DP------DKDDFLGRLSIDLGSVEKKGFIDEWLP 106
RasGAP_IQGAP_like cd05127
Ras-GTPase Activating Domain of IQ motif containing GTPase activating proteins; This family ...
 477-606 4.14e-07

Ras-GTPase Activating Domain of IQ motif containing GTPase activating proteins; This family represents IQ motif containing GTPase activating protein (IQGAP) which associated with the Ras GTP-binding protein. A primary function of IQGAP proteins is to modulate cytoskeletal architecture. There are three known IQGAP family members: IQGAP1, IQGAP2 and IQGAP3. Human IQGAP1 and IQGAP2 share 62% identity. IQGAPs are multi-domain molecules having a calponin-homology (CH) domain which binds F-actin, IQGAP-specific repeats, a single WW domain, four IQ motifs that mediate interactions with calmodulin, and a RasGAP related domain that binds active Rho family GTPases. IQGAP is an essential regulator of cytoskeletal function. IQGAP1 negatively regulates Ras family GTPases by stimulating their intrinsic GTPase activity, the protein actually lacks GAP activity. Both IQGAP1 and IQGAP2 specifically bind to Cdc42 and Rac1, but not to RhoA. Despite of their similarities to part of the sequence of RasGAP, neither IQGAP1 nor IQGAP2 interacts with Ras. IQGAP3, only present in mammals, regulates the organization of the cytoskeleton under the regulation of Rac1 and Cdc42 in neuronal cells. The depletion of IQGAP3 is shown to impair neurite or axon outgrowth in neuronal cells with disorganized cytoskeleton.


Pssm-ID: 213329 [Multi-domain]  Cd Length: 331  Bit Score: 52.97  E-value: 4.14e-07
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 158261639 477 LFLRFLCPAIMSPSLFNLMQEYPDDRTS----RTLTLIAKVIQNLANFAKFGNKEEYMAFMNDFLEHEWGGMKRFLLEIS 552
Cdd:cd05127  179 LYYRYMNPAIVAPEAFDIIDLSVGGQLSplqrRNLGSIAKVLQQAASGKLFGGENPYLSPLNPYISESHEKFKKFFLEAC 258

                         90       100       110       120       130       140
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 158261639 553 NPDTISNTPGFDGYIDLG-----------RELSVLHSLLWEVVSQLDKGENSFLQATVAKLGPLP 606
Cdd:cd05127  259 TVPEAEEHFNIDEYSDLTmltkptiyislQEIFATHKLLLEHQDEIAPDPDDPLRELLDDLGPAP 323
C2A_MCTP_PRT_plant cd04022
C2 domain first repeat found in Multiple C2 domain and Transmembrane region Proteins (MCTP); ...
 175-268 1.02e-05

C2 domain first repeat found in Multiple C2 domain and Transmembrane region Proteins (MCTP); plant subset; MCTPs are involved in Ca2+ signaling at the membrane. Plant-MCTPs are composed of a variable N-terminal sequence, four C2 domains, two transmembrane regions (TMRs), and a short C-terminal sequence. It is one of four protein classes that are anchored to membranes via a transmembrane region; the others being synaptotagmins, extended synaptotagmins, and ferlins. MCTPs are the only membrane-bound C2 domain proteins that contain two functional TMRs. MCTPs are unique in that they bind Ca2+ but not phospholipids. C2 domains fold into an 8-standed beta-sandwich that can adopt 2 structural arrangements: Type I and Type II, distinguished by a circular permutation involving their N- and C-terminal beta strands. Many C2 domains are Ca2+-dependent membrane-targeting modules that bind a wide variety of substances including bind phospholipids, inositol polyphosphates, and intracellular proteins. Most C2 domain proteins are either signal transduction enzymes that contain a single C2 domain, such as protein kinase C, or membrane trafficking proteins which contain at least two C2 domains, such as synaptotagmin 1. However, there are a few exceptions to this including RIM isoforms and some splice variants of piccolo/aczonin and intersectin which only have a single C2 domain. C2 domains with a calcium binding region have negatively charged residues, primarily aspartates, that serve as ligands for calcium ions. This cd contains the first C2 repeat, C2A, and has a type-II topology.


Pssm-ID: 175989 [Multi-domain]  Cd Length: 127  Bit Score: 45.79  E-value: 1.02e-05
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 158261639 175 IIEAKDLAPKKKY-----FCELCLDDTLFaRTTSKTKADNIFWGEHFEF-FSLPP-LHSITVHIYKDVEKRKKKdKNNYV 247
Cdd:cd04022    6 VVDAQDLMPKDGQgsssaYVELDFDGQKK-RTRTKPKDLNPVWNEKLVFnVSDPSrLSNLVLEVYVYNDRRSGR-RRSFL 83

                         90       100
                 ....*....|....*....|..
gi 158261639 248 GLVNIPTASVTGRQ-FVEKWYP 268
Cdd:cd04022   84 GRVRISGTSFVPPSeAVVQRYP 105
RasGAP_IQGAP1 cd05133
Ras-GTPase Activating Domain of IQ motif containing GTPase activating protein 1; IQGAP1 is a ...
 373-619 3.77e-05

Ras-GTPase Activating Domain of IQ motif containing GTPase activating protein 1; IQGAP1 is a homodimeric protein that is widely expressed among vertebrate cell types from early embryogenesis. Mammalian IQGAP1 protein is the best characterized member of the IQGAP family, and contains several protein-interacting domains. Human IQGAP1 is most similar to mouse Iqgap1 (94% identity) and has 62% identity to human IQGAP2. IQGAP1 binds and cross-links actin filaments in vitro and has been implicated in Ca2+/calmodulin signaling, E-cadherin-dependent cell adhesion, cell motility, and invasion. Yeast IQGAP homologs have a role in the recruitment of actin filaments, are components of the spindle pole body, and are required for actomyosin ring assembly and cytokinesis. Furthermore, IQGAP1 over-expression has also been detected in gastric and colorectal carcinomas and gastric cancer cell lines.


Pssm-ID: 213335  Cd Length: 380  Bit Score: 47.35  E-value: 3.77e-05
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 158261639 373 IATKSIEEYLKLVGQqyLHDALGEFIKALYEsdenceVDPSKCSSSELIDHQ-----SNLKMCCELAFCKIINSYCVFP- 446
Cdd:cd05133   85 IKTDPVDIYKSWVNQ--MESQTGEASKLPYD------VTPEQAMSHEEVRTRldasiKNMRMVTDKFLSAIISSVDKIPy 156

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 158261639 447 --RELKEVFASWKQQCLNRGKQDISERLISASLFLRFLCPAIMSPSLFNLM------QEYPDDRtsRTLTLIAKVIQNLA 518
Cdd:cd05133  157 gmRFIAKVLKDTLHEKFPDAGEDELLKIVGNLLYYRYMNPAIVAPDAFDIIdlsaggQLTTDQR--RNLGSIAKMLQHAA 234

                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 158261639 519 NFAKFGNKEEYMAFMNDFLEHEWGGMKRFLLEISNPDTISNTPGFDGYIDLGR-----------ELSVLHSLLWEVVSQL 587
Cdd:cd05133  235 SNKMFLGDNAHLSPINEYLSQSYQKFRRFFQAACDVPELEDKFNVDEYSDLVTltkpviyisigEIINTHTLLLDHQDAI 314

                        250       260       270
                 ....*....|....*....|....*....|..
gi 158261639 588 DKGENSFLQATVAKLGPLPRVLADITKSLTNP 619
Cdd:cd05133  315 APEHNDPIHELLDDLGEVPTIESLIGENPGPP 346
C2C_MCTP_PRT_plant cd04019
C2 domain third repeat found in Multiple C2 domain and Transmembrane region Proteins (MCTP); ...
 171-289 3.85e-05

C2 domain third repeat found in Multiple C2 domain and Transmembrane region Proteins (MCTP); plant subset; MCTPs are involved in Ca2+ signaling at the membrane. Plant-MCTPs are composed of a variable N-terminal sequence, four C2 domains, two transmembrane regions (TMRs), and a short C-terminal sequence. It is one of four protein classes that are anchored to membranes via a transmembrane region; the others being synaptotagmins, extended synaptotagmins, and ferlins. MCTPs are the only membrane-bound C2 domain proteins that contain two functional TMRs. MCTPs are unique in that they bind Ca2+ but not phospholipids. C2 domains fold into an 8-standed beta-sandwich that can adopt 2 structural arrangements: Type I and Type II, distinguished by a circular permutation involving their N- and C-terminal beta strands. Many C2 domains are Ca2+-dependent membrane-targeting modules that bind a wide variety of substances including bind phospholipids, inositol polyphosphates, and intracellular proteins. Most C2 domain proteins are either signal transduction enzymes that contain a single C2 domain, such as protein kinase C, or membrane trafficking proteins which contain at least two C2 domains, such as synaptotagmin 1. However, there are a few exceptions to this including RIM isoforms and some splice variants of piccolo/aczonin and intersectin which only have a single C2 domain. C2 domains with a calcium binding region have negatively charged residues, primarily aspartates, that serve as ligands for calcium ions. This cd contains the third C2 repeat, C2C, and has a type-II topology.


Pssm-ID: 175986 [Multi-domain]  Cd Length: 150  Bit Score: 44.58  E-value: 3.85e-05
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 158261639 171 LRLWIIEAKDLAPK-KKYFCELCLDDTL---FART-TSKTKADNIFWGEHFEFFSLPPLHSitvHIYKDVEKRKKKDKNN 245
Cdd:cd04019    2 LRVTVIEAQDLVPSdKNRVPEVFVKAQLgnqVLRTrPSQTRNGNPSWNEELMFVAAEPFED---HLILSVEDRVGPNKDE 78

                         90       100       110       120       130
                 ....*....|....*....|....*....|....*....|....*....|
gi 158261639 246 YVGLVNIPTASVT----GRQFVEKWYPVSTPT--PNKGKTGGPSIRIKSR 289
Cdd:cd04019   79 PLGRAVIPLNDIErrvdDRPVPSRWFSLERPGgaMEQKKKRKFASRIHLR 128
RasGAP_IQGAP3 cd12207
Ras-GTPase Activating Domain of IQ motif containing GTPase activating protein 3; This family ...
 477-619 6.96e-05

Ras-GTPase Activating Domain of IQ motif containing GTPase activating protein 3; This family represents the IQ motif containing GTPase activating protein 3 (IQGAP3), which associates with Ras GTP-binding proteins. A primary function of IQGAP proteins is to modulate cytoskeletal architecture. There are three known IQGAP family members: IQGAP1, IQGAP2 and IQGAP3. Human IQGAP1 and IQGAP2 share 62% identity. IQGAPs are multi-domain molecules having a calponin-homology (CH) domain which binds F-actin, IQGAP-specific repeats, a single WW domain, four IQ motifs that mediate interactions with calmodulin, and a RasGAP related domain that binds active Rho family GTPases. IQGAP is an essential regulator of cytoskeletal function. IQGAP1 negatively regulates Ras family GTPases by stimulating their intrinsic GTPase activity, the protein actually lacks GAP activity. Both IQGAP1 and IQGAP2 specifically bind to Cdc42 and Rac1, but not to RhoA. Despite of their similarities to part of the sequence of RasGAP, neither IQGAP1 nor IQGAP2 interacts with Ras. IQGAP3, only present in mammals, regulates the organization of the cytoskeleton under the regulation of Rac1 and Cdc42 in neuronal cells. The depletion of IQGAP3 is shown to impair neurite or axon outgrowth in neuronal cells with disorganized cytoskeleton.


Pssm-ID: 213346 [Multi-domain]  Cd Length: 350  Bit Score: 46.36  E-value: 6.96e-05
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 158261639 477 LFLRFLCPAIMSPSLFNLMQE------YPDDRtsRTLTLIAKVIQNLANFAKFGNKEEYMAFMNDFLEHEWGGMKRFLL- 549
Cdd:cd12207  189 LYYRFMNPAVVAPDGFDIVDCsaggalQPEQR--RMLGSVAKVLQHAAANKHFQGDSEHLQALNQYLEETHVKFRKFILq 266

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 158261639 550 --------EISNPDTIS-----NTPGFdgYIDLGrELSVLHSLLWEVVSQLDKGENSFLQATVAKLGPLPRVLADITKSL 616
Cdd:cd12207  267 accvpepeERFNVDEYSemvavAKPVI--YITVG-ELINTHKLLLEHQDSIAPDHSDPLHELLEDLGEVPTVQSLIGESW 343


                 ...
gi 158261639 617 TNP 619
Cdd:cd12207  344 ADL 346
C2A_RasA2_RasA3 cd08401
C2 domain first repeat present in RasA2 and RasA3; RasA2 and RasA3 are GAP1s (GTPase ...
 170-269 4.16e-04

C2 domain first repeat present in RasA2 and RasA3; RasA2 and RasA3 are GAP1s (GTPase activating protein 1s ), Ras-specific GAP members, which suppresses Ras function by enhancing the GTPase activity of Ras proteins resulting in the inactive GDP-bound form of Ras. In this way it can control cellular proliferation and differentiation. RasA2 and RasA3 are both inositol 1,3,4,5-tetrakisphosphate-binding proteins and contain an N-terminal C2 domain, a Ras-GAP domain, a pleckstrin-homology (PH) domain which localizes it to the plasma membrane, and Bruton's Tyrosine Kinase (BTK) a zinc binding domain. C2 domains fold into an 8-standed beta-sandwich that can adopt 2 structural arrangements: Type I and Type II, distinguished by a circular permutation involving their N- and C-terminal beta strands. Many C2 domains are Ca2+-dependent membrane-targeting modules that bind a wide variety of substances including bind phospholipids, inositol polyphosphates, and intracellular proteins. Most C2 domain proteins are either signal transduction enzymes that contain a single C2 domain, such as protein kinase C, or membrane trafficking proteins which contain at least two C2 domains, such as synaptotagmin 1. However, there are a few exceptions to this including RIM isoforms and some splice variants of piccolo/aczonin and intersectin which only have a single C2 domain. C2 domains with a calcium binding region have negatively charged residues, primarily aspartates, that serve as ligands for calcium ions. This cd contains the first C2 repeat, C2A, and has a type-I topology.


Pssm-ID: 176046 [Multi-domain]  Cd Length: 121  Bit Score: 41.27  E-value: 4.16e-04
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 158261639 170 VLRLWIIEAKDLAPKKK------YFCELCLDDTLFARTTSKTKADNIFWGEHFeFFSLP-PLHSITVHIYkdveKRKKKD 242
Cdd:cd08401    1 SLKIKIGEAKNLPPRSGpnkmrdCYCTVNLDQEEVFRTKTVEKSLCPFFGEDF-YFEIPrTFRHLSFYIY----DRDVLR 75

                         90       100
                 ....*....|....*....|....*..
gi 158261639 243 KNNYVGLVNIPTASVTGRQFVEKWYPV 269
Cdd:cd08401   76 RDSVIGKVAIKKEDLHKYYGKDTWFPL 102
C2A_Synaptotagmin-like cd04024
C2 domain first repeat present in Synaptotagmin-like proteins; Synaptotagmin is a ...
 170-291 1.62e-03

C2 domain first repeat present in Synaptotagmin-like proteins; Synaptotagmin is a membrane-trafficking protein characterized by a N-terminal transmembrane region, a linker, and 2 C-terminal C2 domains. Previously all synaptotagmins were thought to be calcium sensors in the regulation of neurotransmitter release and hormone secretion, but it has been shown that not all of them bind calcium. Of the 17 identified synaptotagmins only 8 bind calcium (1-3, 5-7, 9, 10). The function of the two C2 domains that bind calcium are: regulating the fusion step of synaptic vesicle exocytosis (C2A) and binding to phosphatidyl-inositol-3,4,5-triphosphate (PIP3) in the absence of calcium ions and to phosphatidylinositol bisphosphate (PIP2) in their presence (C2B). C2B also regulates also the recycling step of synaptic vesicles. C2 domains fold into an 8-standed beta-sandwich that can adopt 2 structural arrangements: Type I and Type II, distinguished by a circular permutation involving their N- and C-terminal beta strands. Many C2 domains are Ca2+-dependent membrane-targeting modules that bind a wide variety of substances including bind phospholipids, inositol polyphosphates, and intracellular proteins. Most C2 domain proteins are either signal transduction enzymes that contain a single C2 domain, such as protein kinase C, or membrane trafficking proteins which contain at least two C2 domains, such as synaptotagmin 1. However, there are a few exceptions to this including RIM isoforms and some splice variants of piccolo/aczonin and intersectin which only have a single C2 domain. C2 domains with a calcium binding region have negatively charged residues, primarily aspartates, that serve as ligands for calcium ions. This cd contains the first C2 repeat, C2A, and has a type-I topology.


Pssm-ID: 175990 [Multi-domain]  Cd Length: 128  Bit Score: 39.71  E-value: 1.62e-03
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 158261639 170 VLRLWIIEAKDLAPK---KKYFCE----LCLDDTLFaRTTSKTKADNIFWGEHFEFFSLPPLHSITVHIYKDVEKRKKKD 242
Cdd:cd04024    2 VLRVHVVEAKDLAAKdrsGKGKSDpyaiLSVGAQRF-KTQTIPNTLNPKWNYWCEFPIFSAQNQLLKLILWDKDRFAGKD 80

                         90       100       110       120       130
                 ....*....|....*....|....*....|....*....|....*....|..
gi 158261639 243 knnYVGLVNIPTASVTGRQFVE---KWYPVSTPTPnkGKTGGPSIRIKSRFQ 291
Cdd:cd04024   81 ---YLGEFDIALEEVFADGKTGqsdKWITLKSTRP--GKTSVVSGEIHLQFS 127
C2_Smurf-like cd08382
C2 domain present in Smad ubiquitination-related factor (Smurf)-like proteins; A single C2 ...
 171-257 1.64e-03

C2 domain present in Smad ubiquitination-related factor (Smurf)-like proteins; A single C2 domain is found in Smurf proteins, C2-WW-HECT-domain E3s, which play an important role in the downregulation of the TGF-beta signaling pathway. Smurf proteins also regulate cell shape, motility, and polarity by degrading small guanosine triphosphatases (GTPases). C2 domains fold into an 8-standed beta-sandwich that can adopt 2 structural arrangements: Type I and Type II, distinguished by a circular permutation involving their N- and C-terminal beta strands. Many C2 domains are Ca2+-dependent membrane-targeting modules that bind a wide variety of substances including bind phospholipids, inositol polyphosphates, and intracellular proteins. Most C2 domain proteins are either signal transduction enzymes that contain a single C2 domain, such as protein kinase C, or membrane trafficking proteins which contain at least two C2 domains, such as synaptotagmin 1. However, there are a few exceptions to this including RIM isoforms and some splice variants of piccolo/aczonin and intersectin which only have a single C2 domain. C2 domains with a calcium binding region have negatively charged residues, primarily aspartates, that serve as ligands for calcium ions. Members here have type-II topology.


Pssm-ID: 176028 [Multi-domain]  Cd Length: 123  Bit Score: 39.60  E-value: 1.64e-03
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 158261639 171 LRLWIIEAKDLAPKK-----KYFCELCLDDTLFARTTSKTKADNIFWGEHFEFFsLPPLHSITVHIYKdvEKRKKKDKNN 245
Cdd:cd08382    2 VRLTVLCADGLAKRDlfrlpDPFAVITVDGGQTHSTDVAKKTLDPKWNEHFDLT-VGPSSIITIQVFD--QKKFKKKDQG 78

                         90
                 ....*....|..
gi 158261639 246 YVGLVNIPTASV 257
Cdd:cd08382   79 FLGCVRIRANAV 90
PH smart00233
Pleckstrin homology domain; Domain commonly found in eukaryotic signalling proteins. The ...
 113-158 1.81e-03

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


Pssm-ID: 214574 [Multi-domain]  Cd Length: 102  Bit Score: 38.68  E-value: 1.81e-03
                           10        20        30        40
                   ....*....|....*....|....*....|....*....|....*..
gi 158261639   113 VKPLHSSILGQDFCFEVTYLSG-SKCFSCNSASERDKWMENLRRTVQ 158
Cdd:smart00233  56 REAPDPDSSKKPHCFEIKTSDRkTLLLQAESEEEREKWVEALRKAIA 102
PH_RASA1 cd13260
RAS p21 protein activator (GTPase activating protein) 1 Pleckstrin homology (PH) domain; RASA1 ...
 103-155 4.88e-03

RAS p21 protein activator (GTPase activating protein) 1 Pleckstrin homology (PH) domain; RASA1 (also called RasGap1 or p120) is a member of the RasGAP family of GTPase-activating proteins. RASA1 contains N-terminal SH2-SH3-SH2 domains, followed by two C2 domains, a PH domain, a RasGAP domain, and a BTK domain. Splice variants lack the N-terminal domains. It is a cytosolic vertebrate protein that acts as a suppressor of RAS via its C-terminal GAP domain function, enhancing the weak intrinsic GTPase activity of RAS proteins resulting in the inactive GDP-bound form of RAS, allowing control of cellular proliferation and differentiation. Additionally, it is involved in mitogenic signal transmission towards downstream interacting partners through its N-terminal SH2-SH3-SH2 domains. RASA1 interacts with a number of proteins including: G3BP1, SOCS3, ANXA6, Huntingtin, KHDRBS1, Src, EPHB3, EPH receptor B2, Insulin-like growth factor 1 receptor, PTK2B, DOK1, PDGFRB, HCK, Caveolin 2, DNAJA3, HRAS, GNB2L1 and NCK1. 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: 270080  Cd Length: 103  Bit Score: 37.71  E-value: 4.88e-03
                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|....*..
gi 158261639 103 LDLGRGepvSVKPLHSSILGQDFCFE--VTYLSGSKC--FSCNSASERDKWMENLRR 155
Cdd:cd13260   48 IDLSYC---SLYPVHDSLFGRPNCFQivVRALNESTItyLCADTAELAQEWMRALRA 101
C2_PKC_epsilon cd04014
C2 domain in Protein Kinase C (PKC) epsilon; A single C2 domain is found in PKC epsilon. The ...
 171-217 9.36e-03

C2 domain in Protein Kinase C (PKC) epsilon; A single C2 domain is found in PKC epsilon. The PKC family of serine/threonine kinases regulates apoptosis, proliferation, migration, motility, chemo-resistance, and differentiation. There are 3 groups: group 1 (alpha, betaI, beta II, gamma) which require phospholipids and calcium, group 2 (delta, epsilon, theta, eta) which do not require calcium for activation, and group 3 (xi, iota/lambda) which are atypical and can be activated in the absence of diacylglycerol and calcium. C2 domains fold into an 8-standed beta-sandwich that can adopt 2 structural arrangements: Type I and Type II, distinguished by a circular permutation involving their N- and C-terminal beta strands. Many C2 domains are Ca2+-dependent membrane-targeting modules that bind a wide variety of substances including bind phospholipids, inositol polyphosphates, and intracellular proteins. Most C2 domain proteins are either signal transduction enzymes that contain a single C2 domain, such as protein kinase C, or membrane trafficking proteins which contain at least two C2 domains, such as synaptotagmin 1. However, there are a few exceptions to this including RIM isoforms and some splice variants of piccolo/aczonin and intersectin which only have a single C2 domain. C2 domains with a calcium binding region have negatively charged residues, primarily aspartates, that serve as ligands for calcium ions. Members here have a type-II topology.


Pssm-ID: 175981 [Multi-domain]  Cd Length: 132  Bit Score: 37.25  E-value: 9.36e-03
                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|..
gi 158261639 171 LRLWIIEAKDLAP----------KKKYF-----CELCLDDTLFARTTSKTKADNIFWGEHFE 217
Cdd:cd04014    6 LKIKICEAVDLKPtdwstrhavpKKGSQlldpyVSIDVDDTHIGKTSTKPKTNSPVWNEEFT 67
 
Blast search parameters
Data Source: Precalculated data, version = cdd.v.3.21
Preset Options:Database: CDSEARCH/cdd   Low complexity filter: no  Composition Based Adjustment: yes   E-value threshold: 0.01

References:

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