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Conserved domains on  [gi|18859879|ref|NP_573240|]
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uncharacterized protein Dmel_CG42684, isoform B [Drosophila melanogaster]

Protein Classification

C2_SynGAP_like and RasGAP_DAB2IP domain-containing protein (domain architecture ID 11597429)

protein containing domains PH_RasSynGAP-like, C2_SynGAP_like, RasGAP_DAB2IP, and DUF3498

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 ...
412-739 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: 556.04  E-value: 0e+00
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18859879  412 RFQSTDILPINVYGNFLTYLKENYKRVCETLEPVIGVKAKEDIGQALVLLMHAQGLAGAFLTDVVALDLLRVGDQRLTFR 491
Cdd:cd05136    1 RYQSVDILPLEVYKEFLEYLTNNYLDLCEVLEPVLSVKAKEELATALVHILQSTGKAKEFLTDLVMAEVDRLDDEHLIFR 80
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18859879  492 GNSLATKSMEAFLKLTGEQYLQDTLSAPINELIQSERDCEVDPTKTSGSSagSLQRQQAALRGAVRGAWQCIFESHKHFP 571
Cdd:cd05136   81 GNTLATKAMEAYLKLVGQKYLQETLGEFIRALYESEEDCEVDPSKCPPSA--SLSRNQANLRRSVELAWCKILSSHCVFP 158
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18859879  572 AQLRNCFATFRERLQQLGRQDMADNLISASIFLRFLCPAILSPSLFNITSELPSARATRNLTLVAKTLQTLANFTRFQGK 651
Cdd:cd05136  159 RELREVFSSWRERLEERGREDIADRLISASLFLRFLCPAILSPSLFNLTQEYPSERAARNLTLIAKVIQNLANFTRFGGK 238
                        250       260       270       280       290       300       310       320
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18859879  652 ENFMEFLNDFLEQEAARMQQFLEIISTRPEHpapDSILDWAGYIDQGKQLSILHSLLSESLAKLPEARQHELDPLQHILD 731
Cdd:cd05136  239 EEYMEFMNDFVEQEWPNMKQFLQEISSPSPS---SNSSDFDGYIDLGRELSLLHSLLVEIISKLNQTTLDKLGPLPRILN 315

                 ....*...
gi 18859879  732 EISRAKEH 739
Cdd:cd05136  316 DITEALRN 323
C2_SynGAP_like cd04013
C2 domain present in Ras GTPase activating protein (GAP) family; SynGAP, GAP1, RasGAP, and ...
268-421 1.69e-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  Cd Length: 146  Bit Score: 263.78  E-value: 1.69e-80
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18859879  268 PNAEHTRRTDNSLKMWVYEAKNLPPKKRYFCELQLDKTLYGRTSVKLQTDLLFWGEHFDFPDIPEINVITVNVFREVDKK 347
Cdd:cd04013    1 PNRDNSRRTENSLKLWIIEAKGLPPKKRYYCELCLDKTLYARTTSKLKTDTLFWGEHFEFSNLPPVSVITVNLYRESDKK 80
                         90       100       110       120       130       140       150
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 18859879  348 KKRDKYQFVGSVKIPVHDVTSRLPCEQWYPILSDKAGDSLGRtsggggsgSKDKEQLPTLRIKCRFQSTDILPI 421
Cdd:cd04013   81 KKKDKSQLIGTVNIPVTDVSSRQFVEKWYPVSTPKGNGKSGG--------KEGKGESPSIRIKARYQSTRVLPL 146
PH_RasSynGAP-like cd13262
Synaptic Ras-GTPase activating protein family Pleckstrin homology (PH) domain; The RasSynGAP ...
162-276 1.46e-45

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: 163.37  E-value: 1.46e-45
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18859879  162 FTNFFSKKSN-PLKRTKSVTKLERTK------------RGSGGLRGSRSHESLLSSHAVMStiDLSCTGAVGVAPVHQSV 228
Cdd:cd13262    1 ASGFFSRRLKgPLKRTKSVTKLERKSskrlprtrlaraPAGPRLRGSRSHESLLSSSSAAL--DLSADEDVVIRPLHSSI 78
                         90       100       110       120
                 ....*....|....*....|....*....|....*....|....*...
gi 18859879  229 LGRRHCFQVRGGpRGERYYSCGSRQERDLWIYSLRKSIAPNAEHTRRT 276
Cdd:cd13262   79 LGRKHCFQVTTS-EGTRCFSCRSAAERDRWIEDLRRAAQPNKDNCRRT 125
DUF3498 super family cl26404
Domain of unknown function (DUF3498); This presumed domain is functionally uncharacterized. ...
1474-1528 9.45e-12

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: 314820  Cd Length: 502  Bit Score: 69.40  E-value: 9.45e-12
                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....*
gi 18859879   1474 ESTMRSIIDRLITMEEELRREQLKMSLALSHKQRVIEEQGQQIAALDAANSRLLS 1528
Cdd:pfam12004  448 DSQMKSIISRLMAVEEELKKDHAEMQAVIDAKQKIIDAQEKRIASLDAANARLMS 502
 
Name Accession Description Interval E-value
RasGAP_DAB2IP cd05136
Ras-GTPase Activating Domain of DAB2IP and similar proteins; The DAB2IP family of Ras ...
412-739 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: 556.04  E-value: 0e+00
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18859879  412 RFQSTDILPINVYGNFLTYLKENYKRVCETLEPVIGVKAKEDIGQALVLLMHAQGLAGAFLTDVVALDLLRVGDQRLTFR 491
Cdd:cd05136    1 RYQSVDILPLEVYKEFLEYLTNNYLDLCEVLEPVLSVKAKEELATALVHILQSTGKAKEFLTDLVMAEVDRLDDEHLIFR 80
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18859879  492 GNSLATKSMEAFLKLTGEQYLQDTLSAPINELIQSERDCEVDPTKTSGSSagSLQRQQAALRGAVRGAWQCIFESHKHFP 571
Cdd:cd05136   81 GNTLATKAMEAYLKLVGQKYLQETLGEFIRALYESEEDCEVDPSKCPPSA--SLSRNQANLRRSVELAWCKILSSHCVFP 158
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18859879  572 AQLRNCFATFRERLQQLGRQDMADNLISASIFLRFLCPAILSPSLFNITSELPSARATRNLTLVAKTLQTLANFTRFQGK 651
Cdd:cd05136  159 RELREVFSSWRERLEERGREDIADRLISASLFLRFLCPAILSPSLFNLTQEYPSERAARNLTLIAKVIQNLANFTRFGGK 238
                        250       260       270       280       290       300       310       320
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18859879  652 ENFMEFLNDFLEQEAARMQQFLEIISTRPEHpapDSILDWAGYIDQGKQLSILHSLLSESLAKLPEARQHELDPLQHILD 731
Cdd:cd05136  239 EEYMEFMNDFVEQEWPNMKQFLQEISSPSPS---SNSSDFDGYIDLGRELSLLHSLLVEIISKLNQTTLDKLGPLPRILN 315

                 ....*...
gi 18859879  732 EISRAKEH 739
Cdd:cd05136  316 DITEALRN 323
C2_SynGAP_like cd04013
C2 domain present in Ras GTPase activating protein (GAP) family; SynGAP, GAP1, RasGAP, and ...
268-421 1.69e-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  Cd Length: 146  Bit Score: 263.78  E-value: 1.69e-80
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18859879  268 PNAEHTRRTDNSLKMWVYEAKNLPPKKRYFCELQLDKTLYGRTSVKLQTDLLFWGEHFDFPDIPEINVITVNVFREVDKK 347
Cdd:cd04013    1 PNRDNSRRTENSLKLWIIEAKGLPPKKRYYCELCLDKTLYARTTSKLKTDTLFWGEHFEFSNLPPVSVITVNLYRESDKK 80
                         90       100       110       120       130       140       150
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 18859879  348 KKRDKYQFVGSVKIPVHDVTSRLPCEQWYPILSDKAGDSLGRtsggggsgSKDKEQLPTLRIKCRFQSTDILPI 421
Cdd:cd04013   81 KKKDKSQLIGTVNIPVTDVSSRQFVEKWYPVSTPKGNGKSGG--------KEGKGESPSIRIKARYQSTRVLPL 146
RasGAP smart00323
GTPase-activator protein for Ras-like GTPases; All alpha-helical domain that accelerates the ...
403-732 1.20e-78

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: 266.48  E-value: 1.20e-78
                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18859879     403 QLPTLRIKCRFQSTDILPINVYGNFLTYLKENYK-RVCETLEPVIGVKAKEDIGQALVLLMHAQGLAGAFLTDVVALDLL 481
Cdd:smart00323    5 DLGSLRLKTVYTTDFILPSEYYEELLELLLFSLDlSLASALSEVCSGLDKDELATKLVRLFLRRGRGHPFLRALIDPEVE 84
                            90       100       110       120       130       140       150       160
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18859879     482 RVGDQRLTFRGNSLATKSMEAFLKLTGEQYLQDTLSAPINELIQSERDCEVDPTKTSGSSagsLQRQQAALRGAVRGAWQ 561
Cdd:smart00323   85 RTDDPNTIFRGNSLATKSMEVYMKLVGNQYLHTTLKPVLKKIVESKKSCEVDPAKLEGED---LETNLENLLQYVERLFD 161
                           170       180       190       200       210       220       230       240
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18859879     562 CIFESHKHFPAQLRNCFATFRERLQQLGRQ-DMADNLISASIFLRFLCPAILSPSLFNITSELPSARATRNLTLVAKTLQ 640
Cdd:smart00323  162 AIINSSDRLPYGLRDICKQLRQAAEKRFPDaDVIYKAVSSFVFLRFFCPAIVSPKLFNLVDEHPDPTTRRTLTLIAKVLQ 241
                           250       260       270       280       290       300       310       320
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18859879     641 TLANFTRFQGKENFMEFLNDFLEQEAARMQQFLEIIStRPEHPAPDSILDwaGYIDQGKQLSILHSLLSESLAKL--PEA 718
Cdd:smart00323  242 NLANLSEFGSKEPWMEPLNDFLLSHKDRVKDFLDELS-SVPEILVDKVSD--STTISGRELSLLHSLLLENGDALkrELN 318
                           330
                    ....*....|....
gi 18859879     719 RQHELDPLQHILDE 732
Cdd:smart00323  319 NEDPLGKLLFKLRY 332
PH_RasSynGAP-like cd13262
Synaptic Ras-GTPase activating protein family Pleckstrin homology (PH) domain; The RasSynGAP ...
162-276 1.46e-45

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: 163.37  E-value: 1.46e-45
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18859879  162 FTNFFSKKSN-PLKRTKSVTKLERTK------------RGSGGLRGSRSHESLLSSHAVMStiDLSCTGAVGVAPVHQSV 228
Cdd:cd13262    1 ASGFFSRRLKgPLKRTKSVTKLERKSskrlprtrlaraPAGPRLRGSRSHESLLSSSSAAL--DLSADEDVVIRPLHSSI 78
                         90       100       110       120
                 ....*....|....*....|....*....|....*....|....*...
gi 18859879  229 LGRRHCFQVRGGpRGERYYSCGSRQERDLWIYSLRKSIAPNAEHTRRT 276
Cdd:cd13262   79 LGRKHCFQVTTS-EGTRCFSCRSAAERDRWIEDLRRAAQPNKDNCRRT 125
RasGAP pfam00616
GTPase-activator protein for Ras-like GTPase; All alpha-helical domain that accelerates the ...
471-643 3.77e-29

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: 306969  Cd Length: 206  Bit Score: 118.91  E-value: 3.77e-29
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18859879    471 FLTDVVALDLLRVGDQRLTFRGNSLATKSMEAFLKLT-GEQYLQDTLSAPINELIQSE-RDCEVDPTK-----------T 537
Cdd:pfam00616    1 LISELLKEEIESSDSPNDLLRGNSLVSKLLETYNRRTrGQEYLKKILGPLVRKILEDEdLDLESDPVKiyesiinaeelQ 80
                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18859879    538 SGSSAGS-----------------LQRQQAALRGAVRGAWQCIFESHKHFPAQLRNCFATFRERLQQLGRQDMAD---NL 597
Cdd:pfam00616   81 TGRSDLPrdvspeeairdpevrniFEDNLQKLRELADEFLDAIYSSVNRLPYGIRYICKQIYELLEEKFPDATEEeilNA 160
                          170       180       190       200
                   ....*....|....*....|....*....|....*....|....*.
gi 18859879    598 ISASIFLRFLCPAILSPSLFNITSELPSARATRNLTLVAKTLQTLA 643
Cdd:pfam00616  161 IGGFLFLRFINPAIVNPDLFGLVDKQISPKQRRNLTLIAKVLQNLA 206
DUF3498 pfam12004
Domain of unknown function (DUF3498); This presumed domain is functionally uncharacterized. ...
1474-1528 9.45e-12

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: 314820  Cd Length: 502  Bit Score: 69.40  E-value: 9.45e-12
                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....*
gi 18859879   1474 ESTMRSIIDRLITMEEELRREQLKMSLALSHKQRVIEEQGQQIAALDAANSRLLS 1528
Cdd:pfam12004  448 DSQMKSIISRLMAVEEELKKDHAEMQAVIDAKQKIIDAQEKRIASLDAANARLMS 502
C2 pfam00168
C2 domain;
280-378 8.33e-09

C2 domain;


Pssm-ID: 306639  Cd Length: 104  Bit Score: 56.17  E-value: 8.33e-09
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18859879    280 LKMWVYEAKNLPPKKRY-----FCELQLDKTLY-GRTSVKLQTDLLFWGEHFDFP-DIPEINVITVNVFrEVDKKKKRDk 352
Cdd:pfam00168    3 LRVTVIEAKNLPPKDLNgksdpYVKVYLLDGKQkKKTKVVKNTLNPVWNETFTFSvPDPENAVLEIEVY-DYDRFGRDD- 80
                           90       100
                   ....*....|....*....|....*.
gi 18859879    353 yqFVGSVKIPVHDVTSRLPCEQWYPI 378
Cdd:pfam00168   81 --FIGEVRIPLSELDSGEVLDGWYPL 104
C2 smart00239
Protein kinase C conserved region 2 (CalB); Ca2+-binding motif present in phospholipases, ...
279-375 6.39e-08

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  Cd Length: 101  Bit Score: 53.65  E-value: 6.39e-08
                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18859879     279 SLKMWVYEAKNLPPKKRY-----FCELQLDKTLY--GRTSVKLQTDLLFWGEHFDFP-DIPEINVITVNVFrevDKKKKR 350
Cdd:smart00239    1 TLTVKIISARNLPPKDKGgksdpYVKVSLDGDPKekKKTKVVKNTLNPVWNETFEFEvPPPELAELEIEVY---DKDRFG 77
                            90       100
                    ....*....|....*....|....*
gi 18859879     351 DKyQFVGSVKIPVHDVTSRLPCEQW 375
Cdd:smart00239   78 RD-DFIGQVTIPLSDLLLGGRHEKL 101
PH smart00233
Pleckstrin homology domain; Domain commonly found in eukaryotic signalling proteins. The ...
173-267 6.06e-05

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


Pssm-ID: 214574  Cd Length: 102  Bit Score: 44.46  E-value: 6.06e-05
                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18859879     173 LKRTKSVTKLERTKRG----SGGLRGSRSHESLLSSHAVMStIDLSctGAVGVAPVHQSVLGRRHCFQVRGGPRGERYYS 248
Cdd:smart00233    7 LYKKSGGGKKSWKKRYfvlfNSTLLYYKSKKDKKSYKPKGS-IDLS--GCTVREAPDPDSSKKPHCFEIKTSDRKTLLLQ 83
                            90
                    ....*....|....*....
gi 18859879     249 CGSRQERDLWIYSLRKSIA 267
Cdd:smart00233   84 AESEEEREKWVEALRKAIA 102
PH pfam00169
PH domain; PH stands for pleckstrin homology.
203-267 1.28e-03

PH domain; PH stands for pleckstrin homology.


Pssm-ID: 306640  Cd Length: 105  Bit Score: 40.24  E-value: 1.28e-03
                           10        20        30        40        50        60
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 18859879    203 SSHAVMSTIDLSctGAVGVAPVHQSVLGRRHCFQVRGGPRGER---YYSCGSRQERDLWIYSLRKSIA 267
Cdd:pfam00169   40 KSKEPKGSISLS--GCEVVEVVAPDSPKRKFCFELRTGERTGGrtyLLQAESEEERKDWIKAIQSAIR 105
 
Name Accession Description Interval E-value
RasGAP_DAB2IP cd05136
Ras-GTPase Activating Domain of DAB2IP and similar proteins; The DAB2IP family of Ras ...
412-739 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: 556.04  E-value: 0e+00
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18859879  412 RFQSTDILPINVYGNFLTYLKENYKRVCETLEPVIGVKAKEDIGQALVLLMHAQGLAGAFLTDVVALDLLRVGDQRLTFR 491
Cdd:cd05136    1 RYQSVDILPLEVYKEFLEYLTNNYLDLCEVLEPVLSVKAKEELATALVHILQSTGKAKEFLTDLVMAEVDRLDDEHLIFR 80
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18859879  492 GNSLATKSMEAFLKLTGEQYLQDTLSAPINELIQSERDCEVDPTKTSGSSagSLQRQQAALRGAVRGAWQCIFESHKHFP 571
Cdd:cd05136   81 GNTLATKAMEAYLKLVGQKYLQETLGEFIRALYESEEDCEVDPSKCPPSA--SLSRNQANLRRSVELAWCKILSSHCVFP 158
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18859879  572 AQLRNCFATFRERLQQLGRQDMADNLISASIFLRFLCPAILSPSLFNITSELPSARATRNLTLVAKTLQTLANFTRFQGK 651
Cdd:cd05136  159 RELREVFSSWRERLEERGREDIADRLISASLFLRFLCPAILSPSLFNLTQEYPSERAARNLTLIAKVIQNLANFTRFGGK 238
                        250       260       270       280       290       300       310       320
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18859879  652 ENFMEFLNDFLEQEAARMQQFLEIISTRPEHpapDSILDWAGYIDQGKQLSILHSLLSESLAKLPEARQHELDPLQHILD 731
Cdd:cd05136  239 EEYMEFMNDFVEQEWPNMKQFLQEISSPSPS---SNSSDFDGYIDLGRELSLLHSLLVEIISKLNQTTLDKLGPLPRILN 315

                 ....*...
gi 18859879  732 EISRAKEH 739
Cdd:cd05136  316 DITEALRN 323
C2_SynGAP_like cd04013
C2 domain present in Ras GTPase activating protein (GAP) family; SynGAP, GAP1, RasGAP, and ...
268-421 1.69e-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  Cd Length: 146  Bit Score: 263.78  E-value: 1.69e-80
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18859879  268 PNAEHTRRTDNSLKMWVYEAKNLPPKKRYFCELQLDKTLYGRTSVKLQTDLLFWGEHFDFPDIPEINVITVNVFREVDKK 347
Cdd:cd04013    1 PNRDNSRRTENSLKLWIIEAKGLPPKKRYYCELCLDKTLYARTTSKLKTDTLFWGEHFEFSNLPPVSVITVNLYRESDKK 80
                         90       100       110       120       130       140       150
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 18859879  348 KKRDKYQFVGSVKIPVHDVTSRLPCEQWYPILSDKAGDSLGRtsggggsgSKDKEQLPTLRIKCRFQSTDILPI 421
Cdd:cd04013   81 KKKDKSQLIGTVNIPVTDVSSRQFVEKWYPVSTPKGNGKSGG--------KEGKGESPSIRIKARYQSTRVLPL 146
RasGAP smart00323
GTPase-activator protein for Ras-like GTPases; All alpha-helical domain that accelerates the ...
403-732 1.20e-78

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: 266.48  E-value: 1.20e-78
                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18859879     403 QLPTLRIKCRFQSTDILPINVYGNFLTYLKENYK-RVCETLEPVIGVKAKEDIGQALVLLMHAQGLAGAFLTDVVALDLL 481
Cdd:smart00323    5 DLGSLRLKTVYTTDFILPSEYYEELLELLLFSLDlSLASALSEVCSGLDKDELATKLVRLFLRRGRGHPFLRALIDPEVE 84
                            90       100       110       120       130       140       150       160
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18859879     482 RVGDQRLTFRGNSLATKSMEAFLKLTGEQYLQDTLSAPINELIQSERDCEVDPTKTSGSSagsLQRQQAALRGAVRGAWQ 561
Cdd:smart00323   85 RTDDPNTIFRGNSLATKSMEVYMKLVGNQYLHTTLKPVLKKIVESKKSCEVDPAKLEGED---LETNLENLLQYVERLFD 161
                           170       180       190       200       210       220       230       240
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18859879     562 CIFESHKHFPAQLRNCFATFRERLQQLGRQ-DMADNLISASIFLRFLCPAILSPSLFNITSELPSARATRNLTLVAKTLQ 640
Cdd:smart00323  162 AIINSSDRLPYGLRDICKQLRQAAEKRFPDaDVIYKAVSSFVFLRFFCPAIVSPKLFNLVDEHPDPTTRRTLTLIAKVLQ 241
                           250       260       270       280       290       300       310       320
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18859879     641 TLANFTRFQGKENFMEFLNDFLEQEAARMQQFLEIIStRPEHPAPDSILDwaGYIDQGKQLSILHSLLSESLAKL--PEA 718
Cdd:smart00323  242 NLANLSEFGSKEPWMEPLNDFLLSHKDRVKDFLDELS-SVPEILVDKVSD--STTISGRELSLLHSLLLENGDALkrELN 318
                           330
                    ....*....|....
gi 18859879     719 RQHELDPLQHILDE 732
Cdd:smart00323  319 NEDPLGKLLFKLRY 332
RasGAP cd04519
Ras GTPase Activating Domain; RasGAP functions as an enhancer of the hydrolysis of GTP that is ...
429-677 2.68e-63

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: 219.29  E-value: 2.68e-63
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18859879  429 TYLKENYKRVCETLEPVIGVKAKEDIGQALVLLMHAQGLAGAFLTDVVALDLLRVGDQRLTFRGNSLATKSMEAFLKLTG 508
Cdd:cd04519    8 LLLTESPLALLRELSQVLPVKDKEEVATALLRIFESRGLALEFLRYLVRSEVKNTKNPNTLFRGNSLATKLLDQYMKLVG 87
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18859879  509 EQYLQDTLSAPINELIQSERDCEVDPTKTSGssaGSLQRQQAALRGAVRGAWQCIFESHKHFPAQLRNCFATFRERLQQL 588
Cdd:cd04519   88 QEYLKETLSPLIREILESKESCEIDTKLPVG---EDLEENLENLLELVNKLVDRILSSLDRLPPELRYVFKILREFLAER 164
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18859879  589 GRQDM--ADNLISASIFLRFLCPAILSPSLFNITSELPSARATRNLTLVAKTLQTLANFTRFQGKENFMEFLNDFLEQEA 666
Cdd:cd04519  165 FPEEPdeAYQAVSGFLFLRFICPAIVSPELFGLVPDEPSEQARRNLTLISKVLQSLANGVEFGDKEPFMKPLNDFIKSNK 244
                        250
                 ....*....|.
gi 18859879  667 ARMQQFLEIIS 677
Cdd:cd04519  245 PKLKQFLDELS 255
RasGAP_CLA2_BUD2 cd05137
Ras-GTPase Activating Domain of CLA2/BUD2; CLA2/BUD2 functions as a GTPase-activating protein ...
490-680 1.52e-50

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  Cd Length: 356  Bit Score: 185.85  E-value: 1.52e-50
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18859879  490 FRGNSLATKSMEAFLKLTGEQYLQDTLSAPINELIQSERDCEVDPTKTSGSSAGS----LQRQQAALRGAVRGAWQCIFE 565
Cdd:cd05137   96 FRGNSLLTKSLEKYMRRIGKEYLEKSIGDVIRKICEENKDCEVDPSRVKESDSIEkeedLEENWENLISLTEEIWNSIYI 175
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18859879  566 SHKHFPAQLRNCFATFRERLQQLGRQDMAD---NLISASIFLRFLCPAILSPSLFNITSELPSARATRNLTLVAKTLQTL 642
Cdd:cd05137  176 TSNDCPPELRKILKHIRAKVEDRYGDFLRTvtlNSVSGFLFLRFFCPAILNPKLFGLLKDHPRPRAQRTLTLIAKVLQNL 255
                        170       180       190
                 ....*....|....*....|....*....|....*...
gi 18859879  643 ANFTRFQGKENFMEFLNDFLEQEAARMQQFLEIISTRP 680
Cdd:cd05137  256 ANLTTFGQKEPWMEPMNEFLTTHREELKDYIDKITGIK 293
RasGAP_GAP1_like cd05128
Ras-GTPase Activating Domain of GAP1 and similar proteins; The GAP1 family of Ras ...
422-678 3.42e-49

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: 178.98  E-value: 3.42e-49
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18859879  422 NVYGNFLTYLKE--NYKRVCETLEPVIG--VK-AKEDIGQALVLLMHAQGLAGAFLTDVVALDLLRVGDQRLTFRGNSLA 496
Cdd:cd05128    1 QYYEPLLNLLLEslDVPPFTASAVYLLEelVKvDKDDVARPLVRIFLHHGQIVPLLRALASREISKTQDPNTLFRGNSLA 80
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18859879  497 TKSMEAFLKLTGEQYLQDTLSAPINELIQSERDCEVDPTKTsgSSAGSLQRQQAALRGAVRGAWQCIFESHKHFPAQLRN 576
Cdd:cd05128   81 SKCMDEFMKLVGMQYLHETLKPVIDEIFSEKKSCEIDPSKL--KDGEVLETNLANLRGYVERVFKAITSSARRCPTLMCE 158
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18859879  577 CFATFRERLQQlgRQDMADNL----ISASIFLRFLCPAILSPSLFNITSELPSARATRNLTLVAKTLQTLANF----TRF 648
Cdd:cd05128  159 IFSDLRESAAQ--RFPDNEDVpytaVSGFIFLRFFAPAILNPKLFGLREEHPDPQTARTLTLISKTIQTLGNLgsssSGL 236
                        250       260       270
                 ....*....|....*....|....*....|..
gi 18859879  649 QGKENFMEFLND--FLEQEAARMQQFLEIIST 678
Cdd:cd05128  237 GVKEAYMSPLYErfTDEQHVDAVKKFLDRISS 268
PH_RasSynGAP-like cd13262
Synaptic Ras-GTPase activating protein family Pleckstrin homology (PH) domain; The RasSynGAP ...
162-276 1.46e-45

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: 163.37  E-value: 1.46e-45
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18859879  162 FTNFFSKKSN-PLKRTKSVTKLERTK------------RGSGGLRGSRSHESLLSSHAVMStiDLSCTGAVGVAPVHQSV 228
Cdd:cd13262    1 ASGFFSRRLKgPLKRTKSVTKLERKSskrlprtrlaraPAGPRLRGSRSHESLLSSSSAAL--DLSADEDVVIRPLHSSI 78
                         90       100       110       120
                 ....*....|....*....|....*....|....*....|....*...
gi 18859879  229 LGRRHCFQVRGGpRGERYYSCGSRQERDLWIYSLRKSIAPNAEHTRRT 276
Cdd:cd13262   79 LGRKHCFQVTTS-EGTRCFSCRSAAERDRWIEDLRRAAQPNKDNCRRT 125
PH_SynGAP cd13375
Synaptic Ras-GTPase activating protein Pleckstrin homology (PH) domain; SynGAP is a member of ...
165-326 1.12e-42

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: 157.55  E-value: 1.12e-42
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18859879  165 FFSKK-SNPLKRTKSVTKLERTK-----------------RGSGGLRGSRSHESLLSSHAVMSTIDLSCTGAVGVAPVHQ 226
Cdd:cd13375   11 FLSRRlKSSIKRTKSQPKLDRTSsfrqilprfrsadhdraRLMQSFKESHSHESLLSPSSAAEALDLNLDEDSIIKPVHS 90
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18859879  227 SVLGRRHCFQVRGGpRGERYYSCGSRQERDLWIYSLRKSIAPNAEHTRRTDNSLKMWVYEAKNLPPKKRYFCELQLDKTL 306
Cdd:cd13375   91 SILGQEFCFEVTTA-SGTKCFACRSAAERDKWIENLQRAVKPNKDNSRRVDNVLKLWIIEARELPPKKRYYCELCLDDML 169
                        170       180
                 ....*....|....*....|
gi 18859879  307 YGRTSVKLQTDLLFWGEHFD 326
Cdd:cd13375  170 YARTTSKPRTDTVFWGEHFE 189
PH_DAB2IP cd13376
DOC-2/Disabled homolog 2-interacting protein Pleckstrin homology (PH) domain; DAB2IP (also ...
163-326 2.06e-39

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: 147.93  E-value: 2.06e-39
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18859879  163 TNFFSKK-SNPLKRTKSVTKLERTK---------RGSGG--------LRGSRSHESLLSSHAVMSTIDLSCTGAVGVAPV 224
Cdd:cd13376    2 TGFLSRRlKGSIKRTKSQPKLDRNSsfrhilpgfRSVDNershlmprLKESRSHESLLSPSSAVEALDLSMEEEVVIKPV 81
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18859879  225 HQSVLGRRHCFQVRGGPrGERYYSCGSRQERDLWIYSLRKSIAPNAEHTRRTDNSLKMWVYEAKNLPPKKRYFCELQLDK 304
Cdd:cd13376   82 HSSILGQDYCFEVTTSS-GSKCFSCRSAAERDKWMENLRRAVHPNKDNSRRVENMLKLWIIEAKDLPAKKKYLCELCLDD 160
                        170       180
                 ....*....|....*....|..
gi 18859879  305 TLYGRTSVKLQTDLLFWGEHFD 326
Cdd:cd13376  161 VLYARTTCKLKTDNVFWGEHFE 182
RasGAP_p120GAP cd05391
Ras-GTPase Activating Domain of p120; p120GAP is a negative regulator of Ras that stimulates ...
455-723 1.90e-38

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: 149.56  E-value: 1.90e-38
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18859879  455 GQALVLLmhAQGLAGAFLTDVVALDLLRVGDQR---------LTFRGNSLATKSMEAFLKLTGEQYLQDTLSAPINELIQ 525
Cdd:cd05391   33 GQDRTLL--ASILLRIFRHEKLESLLLRTLNDReismedeatTLFRATTLASTLMEQYMKATATPFVHHALKDTILKILE 110
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18859879  526 SERDCEVDPTKTSGSSAGSLQRQQaaLRGAVRGAWQCIFESHKHFPAQLRNCFATFRERLQQL--GRQDMADNLISASIF 603
Cdd:cd05391  111 SKQSCELNPSKLEKNEDVNTNLEH--LLNILSELVEKIFMAAEILPPTLRYIYGCLQKSVQQKwpTNTTVRTRVVSGFVF 188
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18859879  604 LRFLCPAILSPSLFNITSELPSARATRNLTLVAKTLQTLANFTRFQGKENFMEFLNDFLEQEAARMQQFLEIISTRP--- 680
Cdd:cd05391  189 LRLICPAILNPRMFNIISETPSPTAARTLTLVAKSLQNLANLVEFGAKEPYMEGVNPFIKKNKERMIMFLDELGNVPelp 268
                        250       260       270       280       290
                 ....*....|....*....|....*....|....*....|....*....|...
gi 18859879  681 ---EHPAPDSILDWAG-------YIDQGKQLSILHSLLSESLAKLPEARQHEL 723
Cdd:cd05391  269 dttEHSRTDLSRDLAAlheicvaHSDELRTLSNERGALKKLLAVTELLQQKQN 321
RasGAP_RASAL cd05135
Ras-GTPase Activating Domain of RASAL1 and similar proteins; Ras GTPase activating-like ...
442-674 1.26e-37

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: 146.11  E-value: 1.26e-37
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18859879  442 LEPVIGVKAKEDIGQALVLLMHAQGLAGAFLTDVVALDLLRVGDQRLTFRGNSLATKSMEAFLKLTGEQYLQDTLSAPIN 521
Cdd:cd05135   31 LEEVTTGESRQDVATKLVKIFLGQGLVVPFLDYLNTREVGRTTDPNTLFRSNSLASKSMEQFMKVVGMPYLHEVLKPVIN 110
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18859879  522 ELIQSERDCEVDPTKTS------GSSAGSLQRQQ------AALRGAVRGAWQCIFESHKHFPAQLRNCFATFR----ERL 585
Cdd:cd05135  111 RIFEEKKYVELDPCKIDlnrtrrISFKGSLSEAQvresslELLQGYLGSIIDAIVGSVDQCPPVMRVAFKQLHkrveERF 190
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18859879  586 QQLGRQDMADNLISASIFLRFLCPAILSPSLFNITSELPSARATRNLTLVAKTLQTLANFTR--FQGKENFMEFLNDFLE 663
Cdd:cd05135  191 PEAEHQDVKYLAISGFLFLRFFAPAILTPKLFQLREQHADPRTSRTLLLLAKAVQSIGNLGLqlGQGKEQWMAPLHPFIL 270
                        250
                 ....*....|.
gi 18859879  664 QEAARMQQFLE 674
Cdd:cd05135  271 QSVARVKDFLD 281
RasGAP_Neurofibromin_like cd05392
Ras-GTPase Activating Domain of proteins similar to neurofibromin; Neurofibromin-like proteins ...
424-680 4.86e-37

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: 145.12  E-value: 4.86e-37
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18859879  424 YGNFLTYLKENYKRVCETLEpVIGVKAKEDIGQALVLLMHAQGLAGAFLTDVVALDLLRVGDQRLTFRGNSLATKSMEAF 503
Cdd:cd05392    6 YDELLELLIEDPQLLLAIAE-VCPSSEVDLLAQSLLNLFETRNRLLPLISWLIEDEISHTSRAADLFRRNSVATRLLTLY 84
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18859879  504 LKLTGEQYLQDTLSAPINELIQSERDCEVDPTKTSGSSagsLQRQQAALRGAVRGAWQCIFESHKHFPAQLRNCFATFRE 583
Cdd:cd05392   85 AKSVGNKYLRKVLRPLLTEIVDNKDYFEVEKIKPDDEN---LEENADLLMKYAQMLLDSITDSVDQLPPSFRYICNTIYE 161
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18859879  584 RLQQLgRQDMADNLISASIFLRFLCPAILSPSLFNITSELPSARATRNLTLVAKTLQTLANFTRFQGKENFMEFLNDFLE 663
Cdd:cd05392  162 SVSKK-FPDAALIAVGGFLFLRFICPAIVSPESENLLDPPPTPEARRSLILIAKVLQNIANGVLFSLKEPYLESLNEFLK 240
                        250
                 ....*....|....*..
gi 18859879  664 QEAARMQQFLEIISTRP 680
Cdd:cd05392  241 KNSDRIQQFLSEVSTIP 257
RasGAP_RASA3 cd05134
Ras-GTPase Activating Domain of RASA3; RASA3 (or GAP1_IP4BP) is a member of the GAP1 family ...
449-678 7.30e-35

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: 137.46  E-value: 7.30e-35
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18859879  449 KAKEDIGQALVLLMHAQGLAGAFLTDVVALDLLRVGDQRLTFRGNSLATKSMEAFLKLTGEQYLQDTLSAPINELIQSER 528
Cdd:cd05134   33 REKQEAAIPLVRLFLHYGKIVPFISAIASAEVNRTQDPNTIFRGNSLTSKCIDETMKLAGMHYLQVTLKPIIDEICQEHK 112
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18859879  529 DCEVDPTKTSGSSagSLQRQQAALRGAVRGAWQCIFESHKHFPAQLRNCFATFRE----RLQqlGRQDMADNLISASIFL 604
Cdd:cd05134  113 PCEIDPVKLKDGE--NLENNRENLRQYVDRIFRVITKSGVSCPTVMCDIFFSLREsaakRFQ--VDPDVRYTAVSSFIFL 188
                        170       180       190       200       210       220       230
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 18859879  605 RFLCPAILSPSLFNITSELPSARATRNLTLVAKTLQTLANFTRFQG---KENFM-EFLNDFLEQE-AARMQQFLEIIST 678
Cdd:cd05134  189 RFFAPAILSPNLFQLTPHHPDPQTSRTLTLISKTIQTLGSLSKSKSanfKESYMaAFYDYFNEQKyADAVKNFLDLISS 267
RasGAP_Neurofibromin cd05130
Ras-GTPase Activating Domain of neurofibromin; Neurofibromin is the product of the ...
453-714 4.34e-31

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  Cd Length: 332  Bit Score: 127.82  E-value: 4.34e-31
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18859879  453 DIGQALVLLMHAQGLAGAFLTDVVALDLLRVGDQRLTFRGNSLATKSMEAFLKLTGEQYLQDTLSAPINELIQSER--DC 530
Cdd:cd05130   41 ELARVLVTLFDSKHLLYQLLWNMFSKEVELADSMQTLFRGNSLASKIMTFCFKVYGATYLQSLLEPLLRTMITSSEwvSY 120
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18859879  531 EVDPTKTSGSSagSLQRQQAALRGAVRGAWQCIFESHKHFPAQLRNCFATFRERLQQLGRQDMADNLISAsIFLRFLCPA 610
Cdd:cd05130  121 EVDPTRLEGNE--NLEENQRNLLQLTEKFFHAIISSSDEFPPQLRSVCHCLYQVVSHRFPNSGLGAVGSA-IFLRFINPA 197
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18859879  611 ILSPSLFNITSELPSARATRNLTLVAKTLQTLANFTRFQgKENFMEFLNDFLEQEAARMQQFLEIIST------RPEHPA 684
Cdd:cd05130  198 IVSPYEYGILDREPPPRVKRGLKLMSKILQNIANHVLFT-KEAHMLPFNDFLRNHFEAGRRFFSSIASdcgavdGPSSKY 276
                        250       260       270
                 ....*....|....*....|....*....|
gi 18859879  685 PDSILDWagyidqgkQLSILHSLLSESLAK 714
Cdd:cd05130  277 LSFINDA--------NVLALHRLLWNNQEK 298
RasGAP_RASA4 cd05395
Ras-GTPase Activating Domain of RASA4; Ras GTPase activating-like 4 protein (RASAL4), also ...
442-673 2.34e-29

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  Cd Length: 287  Bit Score: 121.52  E-value: 2.34e-29
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18859879  442 LEPVIGVKAKEDIGQALVLLMHAQGLAGAFLTDVVALDLLRVGDQRLTFRGNSLATKSMEAFLKLTGEQYLQDTLSAPIN 521
Cdd:cd05395   31 IDETTTAECRQEVATNLVKLFLGQGLAKEFLDLLFQLELDKTTEPNTLFRSNSLASKSMESFLKVAGMQYLHSVLGPTIN 110
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18859879  522 ELIQSERDCEVDPTKTSGSSAG--SLQRQQAA----------LRGAVRGAWQCIFESHKHFPAQLRNCFATFRERLQQL- 588
Cdd:cd05395  111 RVFEEKKYVELDPSKVEIKDVGcsGLHRIQTEsevieqsaqlLQSYLGELLSAISKSVKYCPAVIRATFRQLFKRVQERf 190
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18859879  589 -GRQDMADNLISASIF--LRFLCPAILSPSLFNITSELPSARATRNLTLVAKTLQTLANFTRFQG--KENFMEFLNDFLE 663
Cdd:cd05395  191 pENQHQNVKFIAVTSFlcLRFFSPAIMSPKLFHLREKHADARTSRTLLLLAKAVQNVGNMDTLASraKEAWMAPLQPAIQ 270
                        250
                 ....*....|
gi 18859879  664 QEAARMQQFL 673
Cdd:cd05395  271 QGVAQLKDFI 280
RasGAP_RASA2 cd05394
Ras-GTPase Activating Domain of RASA2; RASA2 (or GAP1(m)) is a member of the GAP1 family of ...
460-678 2.54e-29

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: 121.15  E-value: 2.54e-29
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18859879  460 LLMHAQGLAgAFLTDVVALDLLRVGDQRLTFRGNSLATKSMEAFLKLTGEQYLQDTLSAPINELIQSERDCEVDPTKTsg 539
Cdd:cd05394   45 LLLHHNKLV-PFVAAVAALDLKDTQEANTIFRGNSLATRCLDEMMKIVGKHYLKVTLKPVLDEICESPKPCEIDPIKL-- 121
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18859879  540 SSAGSLQRQQAALRGAVRGAWQCIFESHKHFPAQLRNCFATFRERLQQLGRQD--MADNLISASIFLRFLCPAILSPSLF 617
Cdd:cd05394  122 KEGDNVENNKENLRYYVDKVFFSIVKSSMSCPTLMCDVFRSLRHLAVKRFPNDphVQYSAVSSFVFLRFFAVAVVSPHTF 201
                        170       180       190       200       210       220
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 18859879  618 NITSELPSARATRNLTLVAKTLQTLANFTRFQG------KENFM-EFLNDFLEQE-AARMQQFLEIIST 678
Cdd:cd05394  202 QLRPHHPDAQTSRTLTLISKTIQTLGSWGSLSKsklssfKETFMcDFFKMFQEEKyIEKVKKFLDEISS 270
RasGAP pfam00616
GTPase-activator protein for Ras-like GTPase; All alpha-helical domain that accelerates the ...
471-643 3.77e-29

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: 306969  Cd Length: 206  Bit Score: 118.91  E-value: 3.77e-29
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18859879    471 FLTDVVALDLLRVGDQRLTFRGNSLATKSMEAFLKLT-GEQYLQDTLSAPINELIQSE-RDCEVDPTK-----------T 537
Cdd:pfam00616    1 LISELLKEEIESSDSPNDLLRGNSLVSKLLETYNRRTrGQEYLKKILGPLVRKILEDEdLDLESDPVKiyesiinaeelQ 80
                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18859879    538 SGSSAGS-----------------LQRQQAALRGAVRGAWQCIFESHKHFPAQLRNCFATFRERLQQLGRQDMAD---NL 597
Cdd:pfam00616   81 TGRSDLPrdvspeeairdpevrniFEDNLQKLRELADEFLDAIYSSVNRLPYGIRYICKQIYELLEEKFPDATEEeilNA 160
                          170       180       190       200
                   ....*....|....*....|....*....|....*....|....*.
gi 18859879    598 ISASIFLRFLCPAILSPSLFNITSELPSARATRNLTLVAKTLQTLA 643
Cdd:pfam00616  161 IGGFLFLRFINPAIVNPDLFGLVDKQISPKQRRNLTLIAKVLQNLA 206
PH_RASAL3 cd13374
RAS protein activator like-3 Pleckstrin homology (PH) domain; RASAL3 is thought to be a Ras ...
151-291 2.67e-23

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: 100.09  E-value: 2.67e-23
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18859879  151 QHQTEHNATSrfTNFFSKKSNPLKRTKSVTK--LERTKRGSGGLRGSR-SHESLlsshAVMSTIDLSCTGAVGVAPVHQS 227
Cdd:cd13374    6 PGKTEPEAAG--PNQGHNVRGLLKRLKEKKKakAESTGTGRDGPPSALgSRESL----ATISELDLGAERDVRVWPLHPS 79
                         90       100       110       120       130       140
                 ....*....|....*....|....*....|....*....|....*....|....*....|....
gi 18859879  228 VLGRRHCFQVRGgPRGERYYSCGSRQERDLWIYSLRKSIAPNAEHTRRTDNSLKMWVYEAKNLP 291
Cdd:cd13374   80 LLGEPHCFQVTW-PGGSRCFSCRSAAERDRWIEDLRRSFQPHQDNVEREETWLSVWVHEAKGLP 142
RasGAP_GAPA cd05132
Ras-GTPase Activating Domain of GAPA; GAPA is an IQGAP-related protein and is predicted to ...
508-736 1.24e-21

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: 98.96  E-value: 1.24e-21
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18859879  508 GEQYLQDTLSAPINELIQ-SERDCEVDPTK----------TSGSSAGSLQR----QQAALRGAVRGAWQ----------- 561
Cdd:cd05132   67 GQSYLKTVLADRINDLISlKDLNLEINPLKvyeqmindieLDTGLPSNLPRgitpEEAAENPAVQNIIEprlemleeitn 146
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18859879  562 ----CIFESHKHFP-------AQLRNcfaTFRERLQQLGRQDMAdNLISASIFLRFLCPAILSPSLFNITSELPSARATR 630
Cdd:cd05132  147 sfleAIINSLDEVPygirwicKQIRS---LTRRKFPDASDETIC-SLIGGFFLLRFINPAIVSPQAYMLVDGKPSDNTRR 222
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18859879  631 NLTLVAKTLQTLANFTRFQgKENFMEFLNDFLEQEAARMQQFLEIISTRP---EHpapdsiLDWAGYIDQGKQ---LSI- 703
Cdd:cd05132  223 TLTLIAKLLQNLANKPSYS-KEPYMAPLQPFVEENKERLNKFLNDLCEVDdfyES------LELDQYIALSKKdlsINIt 295
                        250       260       270       280
                 ....*....|....*....|....*....|....*....|
gi 18859879  704 ------LHSLLSESLAKL-PEarqhELDPLQHILDEISRA 736
Cdd:cd05132  296 lneiynTHSLLVKHLAELaPD----HNDHLRLILQELGPA 331
PH_nGAP cd13373
Neuronal growth-associated proteins Pleckstrin homology (PH) domain; nGAP (also called RASAL2 ...
161-282 9.24e-20

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: 89.40  E-value: 9.24e-20
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18859879  161 RFTNFFSKK-SNPLKRTKSVTKLERT--------------KRGSGGLRGSRSHESLLSSHAVMSTIDLSCTGAVGVAPVH 225
Cdd:cd13373    3 KVSGFFSKRlKGSIKRTKSQSKLDRNtsfrlpslrsaddrSRGLPKLKESRSHESLLSPGSAVEALDLGREEKVSVKPLH 82
                         90       100       110       120       130
                 ....*....|....*....|....*....|....*....|....*....|....*..
gi 18859879  226 QSVLGRRHCFQVRGGpRGERYYSCGSRQERDLWIYSLRKSIAPNAEHTRRTDNSLKM 282
Cdd:cd13373   83 SSILGQDFCFEVTYS-SGSKCFSCSSAAERDKWMENLRRTVQPNKDNCRRAENVLRL 138
DUF3498 pfam12004
Domain of unknown function (DUF3498); This presumed domain is functionally uncharacterized. ...
1474-1528 9.45e-12

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: 314820  Cd Length: 502  Bit Score: 69.40  E-value: 9.45e-12
                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....*
gi 18859879   1474 ESTMRSIIDRLITMEEELRREQLKMSLALSHKQRVIEEQGQQIAALDAANSRLLS 1528
Cdd:pfam12004  448 DSQMKSIISRLMAVEEELKKDHAEMQAVIDAKQKIIDAQEKRIASLDAANARLMS 502
C2 cd00030
C2 domain; The C2 domain was first identified in PKC. C2 domains fold into an 8-standed ...
280-378 2.61e-10

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  Cd Length: 102  Bit Score: 60.54  E-value: 2.61e-10
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18859879  280 LKMWVYEAKNLPPKKR-----YFCELQLDKTLYGRTSVKLQTDLLFWGEHFDFPDIPEIN-VITVNVFREvDKKKKRDky 353
Cdd:cd00030    1 LRVTVIEARNLPAKDLngksdPYVKVSLGGKQKFKTKVVKNTLNPVWNETFEFPVLDPESdTLTVEVWDK-DRFSKDD-- 77
                         90       100
                 ....*....|....*....|....*.
gi 18859879  354 qFVGSVKIPVHDV-TSRLPCEQWYPI 378
Cdd:cd00030   78 -FLGEVEIPLSELlDSGKEGELWLPL 102
RasGAP_RAP6 cd05129
Ras-GTPase Activating Domain of Rab5-activating protein 6; Rab5-activating protein 6 (RAP6) is ...
424-689 3.21e-09

Ras-GTPase Activating Domain of Rab5-activating protein 6; Rab5-activating protein 6 (RAP6) is an endosomal protein with a role in the regulation of receptor-mediated endocytosis. RAP6 contains a Vps9 domain, which is involved in the activation of Rab5, and a Ras GAP domain (RGD). Rab5 is a small GTPase required for the control of the endocytic route, and its activity is regulated by guanine nucleotide exchange factor, such as Rabex5, and GAPs, such as RN-tre. Human Rap6 protein is localized on the plasma membrane and on the endosome. RAP6 binds to Rab5 and Ras through the Vps9 and RGD domains, respectively.


Pssm-ID: 213331  Cd Length: 365  Bit Score: 60.43  E-value: 3.21e-09
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18859879  424 YGNFLTYLKENYKRVCETLepVIGVKAKEDIGQALVLLMhAQGLAG-AFLTD-----------VVALDLLRVGDQRLTFR 491
Cdd:cd05129   13 YGEFLRILRENPQLLAECL--ARGEKLSLEQTQNVIQTI-VTSLYGnCIMPEderlllqllreLMELQLKKSDNPRRLLR 89
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18859879  492 GNSLA-TKSMEAF--LKLTGEQYLQDTLSAPINELIQSERD-CEVDPTKTSGSSAGSLQ--------------RQQAA-- 551
Cdd:cd05129   90 KGSCAfSRVFKLFteLLFSAKLYLTAALHKPIMQVLVDDEIfLETDPQKALCRFSPAEQekrfgeegtpeqqrKLQQYra 169
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18859879  552 -----LRGAVRGAWQCIFESHKHFPAQLRNCFATFRERLQQLGRQDMAD--NLISASIFLRFLCPAILSPSLFNITSELP 624
Cdd:cd05129  170 eflsrLVALVNKFISSLRQSVYCFPQSLRWIVRQLRKILTRSGDDEEAEarALCTDLLFTNFICPAIVNPEQYGIISDAP 249
                        250       260       270       280       290       300
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 18859879  625 SARATR-NLTLVAKTLQTLA--NFTRFQgkENFMEFLNDFleqEAARMQQFLE-IISTRPEHPAPDSIL 689
Cdd:cd05129  250 ISEVARhNLMQVAQILQVLAltEFESPD--PRLKELLSKF---DKDCVSAFLDvVIVGRAVETPPPSSS 313
RasGAP_IQGAP_like cd05127
Ras-GTPase Activating Domain of IQ motif containing GTPase activating proteins; This family ...
602-738 3.66e-09

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  Cd Length: 331  Bit Score: 59.91  E-value: 3.66e-09
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18859879  602 IFLRFLCPAILSPSLFNITS----ELPSARATRNLTLVAKTLQTLANFTRFQGKENFMEFLNDFLEQEAARMQQFLEIIS 677
Cdd:cd05127  179 LYYRYMNPAIVAPEAFDIIDlsvgGQLSPLQRRNLGSIAKVLQQAASGKLFGGENPYLSPLNPYISESHEKFKKFFLEAC 258
                         90       100       110       120       130       140       150
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|.
gi 18859879  678 TRP---EHPAPDSILDWagYIDQGKQLSI-------LHSLLSESLAKLPEARQhelDPLQHILDEISRAKE 738
Cdd:cd05127  259 TVPeaeEHFNIDEYSDL--TMLTKPTIYIslqeifaTHKLLLEHQDEIAPDPD---DPLRELLDDLGPAPT 324
C2 pfam00168
C2 domain;
280-378 8.33e-09

C2 domain;


Pssm-ID: 306639  Cd Length: 104  Bit Score: 56.17  E-value: 8.33e-09
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18859879    280 LKMWVYEAKNLPPKKRY-----FCELQLDKTLY-GRTSVKLQTDLLFWGEHFDFP-DIPEINVITVNVFrEVDKKKKRDk 352
Cdd:pfam00168    3 LRVTVIEAKNLPPKDLNgksdpYVKVYLLDGKQkKKTKVVKNTLNPVWNETFTFSvPDPENAVLEIEVY-DYDRFGRDD- 80
                           90       100
                   ....*....|....*....|....*.
gi 18859879    353 yqFVGSVKIPVHDVTSRLPCEQWYPI 378
Cdd:pfam00168   81 --FIGEVRIPLSELDSGEVLDGWYPL 104
C2 smart00239
Protein kinase C conserved region 2 (CalB); Ca2+-binding motif present in phospholipases, ...
279-375 6.39e-08

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  Cd Length: 101  Bit Score: 53.65  E-value: 6.39e-08
                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18859879     279 SLKMWVYEAKNLPPKKRY-----FCELQLDKTLY--GRTSVKLQTDLLFWGEHFDFP-DIPEINVITVNVFrevDKKKKR 350
Cdd:smart00239    1 TLTVKIISARNLPPKDKGgksdpYVKVSLDGDPKekKKTKVVKNTLNPVWNETFEFEvPPPELAELEIEVY---DKDRFG 77
                            90       100
                    ....*....|....*....|....*
gi 18859879     351 DKyQFVGSVKIPVHDVTSRLPCEQW 375
Cdd:smart00239   78 RD-DFIGQVTIPLSDLLLGGRHEKL 101
C2_Ras_p21A1 cd08400
C2 domain present in RAS p21 protein activator 1 (RasA1); RasA1 is a GAP1 (GTPase activating ...
279-380 2.48e-07

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  Cd Length: 126  Bit Score: 51.98  E-value: 2.48e-07
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18859879  279 SLKMWVYEAKNLPPKK--RYFCELQLDKTLYGRTSVKLQTDLLfWGEHFDFPDIP-EINVITVnvfrEVDKKKKRDKYQF 355
Cdd:cd08400    5 SLQLNVLEAHKLPVKHvpHPYCVISLNEVKVARTKVREGPNPV-WSEEFVFDDLPpDVNSFTI----SLSNKAKRSKDSE 79
                         90       100
                 ....*....|....*....|....*
gi 18859879  356 VGSVKIPVHDVTSRLPCEQWYPILS 380
Cdd:cd08400   80 IAEVTVQLSKLQNGQETDEWYPLSS 104
C2A_RasGAP cd08383
C2 domain (first repeat) of Ras GTPase activating proteins (GAPs); RasGAPs suppress Ras ...
279-378 5.71e-07

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  Cd Length: 117  Bit Score: 50.73  E-value: 5.71e-07
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18859879  279 SLKMWVYEAKNLPPKK--RYFCELQLDKTLYGRTSVKLQTDlLFWGEHFDFPDIP-EINVITVNVFREVDKKKKRDkyqf 355
Cdd:cd08383    1 SLRLRILEAKNLPSKGtrDPYCTVSLDQVEVARTKTVEKLN-PFWGEEFVFDDPPpDVTFFTLSFYNKDKRSKDRD---- 75
                         90       100
                 ....*....|....*....|....*..
gi 18859879  356 VGSVKIPVhdvtSRLP----CEQWYPI 378
Cdd:cd08383   76 IVIGKVAL----SKLDlgqgKDEWFPL 98
C2A_RasA2_RasA3 cd08401
C2 domain first repeat present in RasA2 and RasA3; RasA2 and RasA3 are GAP1s (GTPase ...
279-378 3.76e-06

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  Cd Length: 121  Bit Score: 48.20  E-value: 3.76e-06
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18859879  279 SLKMWVYEAKNLPPKKR------YFCELQLDKTLYGRTSVKLQTDLLFWGEHFDFpDIP-EINVITVNVF-REVDKKKKR 350
Cdd:cd08401    1 SLKIKIGEAKNLPPRSGpnkmrdCYCTVNLDQEEVFRTKTVEKSLCPFFGEDFYF-EIPrTFRHLSFYIYdRDVLRRDSV 79
                         90       100
                 ....*....|....*....|....*...
gi 18859879  351 dkyqfVGSVKIPVHDVTSRLPCEQWYPI 378
Cdd:cd08401   80 -----IGKVAIKKEDLHKYYGKDTWFPL 102
RasGAP_IQGAP2 cd05131
Ras-GTPase Activating Domain of IQ motif containing GTPase activating protein 2; IQGAP2 is a ...
545-681 8.47e-06

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  Cd Length: 359  Bit Score: 49.61  E-value: 8.47e-06
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18859879  545 LQRQQAALRGAVRGAWQCIFESHKHFPAQLRNCFATFRERLQQLGRQDMADNL---ISASIFLRFLCPAILSPSLFNITS 621
Cdd:cd05131  129 LESSIQSLRSVTDKVLGSIFSSLDLIPYGMRYIAKVLKNSLHEKFPDATEDELlkiVGNLLYYRYMNPAIVAPDGFDIID 208
                         90       100       110       120       130       140
                 ....*....|....*....|....*....|....*....|....*....|....*....|....
gi 18859879  622 ELPSAR----ATRNLTLVAKTLQTLANFTRFQGKENFMEFLNDFLEQEAARMQQFLEIISTRPE 681
Cdd:cd05131  209 MTAGGQihseQRRNLGSVAKVLQHAASNKLFEGENAHLSSMNSYLSQTYQKFRKFFQAACDVPE 272
RasGAP_IQGAP1 cd05133
Ras-GTPase Activating Domain of IQ motif containing GTPase activating protein 1; IQGAP1 is a ...
580-733 3.14e-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: 48.12  E-value: 3.14e-05
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18859879  580 TFRERLQQLGRQDMAdNLISASIFLRFLCPAILSPSLFNITSELPSARAT----RNLTLVAKTLQTLANFTRFQGKENFM 655
Cdd:cd05133  168 TLHEKFPDAGEDELL-KIVGNLLYYRYMNPAIVAPDAFDIIDLSAGGQLTtdqrRNLGSIAKMLQHAASNKMFLGDNAHL 246
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18859879  656 EFLNDFLEQEAARMQQFLEIISTRPEHPAPDSILDWAG---------YIDQGKQLSILHSLLSESLAKLPEARqhelDPL 726
Cdd:cd05133  247 SPINEYLSQSYQKFRRFFQAACDVPELEDKFNVDEYSDlvtltkpviYISIGEIINTHTLLLDHQDAIAPEHN----DPI 322

                 ....*..
gi 18859879  727 QHILDEI 733
Cdd:cd05133  323 HELLDDL 329
PH_RASA1 cd13260
RAS p21 protein activator (GTPase activating protein) 1 Pleckstrin homology (PH) domain; RASA1 ...
211-264 5.77e-05

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: 44.64  E-value: 5.77e-05
                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|....*..
gi 18859879  211 IDLSCTGavgVAPVHQSVLGRRHCFQ--VRGGPRGERYYSCGSRQE-RDLWIYSLRK 264
Cdd:cd13260   48 IDLSYCS---LYPVHDSLFGRPNCFQivVRALNESTITYLCADTAElAQEWMRALRA 101
PH smart00233
Pleckstrin homology domain; Domain commonly found in eukaryotic signalling proteins. The ...
173-267 6.06e-05

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


Pssm-ID: 214574  Cd Length: 102  Bit Score: 44.46  E-value: 6.06e-05
                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18859879     173 LKRTKSVTKLERTKRG----SGGLRGSRSHESLLSSHAVMStIDLSctGAVGVAPVHQSVLGRRHCFQVRGGPRGERYYS 248
Cdd:smart00233    7 LYKKSGGGKKSWKKRYfvlfNSTLLYYKSKKDKKSYKPKGS-IDLS--GCTVREAPDPDSSKKPHCFEIKTSDRKTLLLQ 83
                            90
                    ....*....|....*....
gi 18859879     249 CGSRQERDLWIYSLRKSIA 267
Cdd:smart00233   84 AESEEEREKWVEALRKAIA 102
C2_Smurf-like cd08382
C2 domain present in Smad ubiquitination-related factor (Smurf)-like proteins; A single C2 ...
321-366 1.83e-04

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  Cd Length: 123  Bit Score: 43.06  E-value: 1.83e-04
                         10        20        30        40
                 ....*....|....*....|....*....|....*....|....*..
gi 18859879  321 WGEHFDFPDIPEiNVITVNVFrevDKKKKRDKYQ-FVGSVKIPVHDV 366
Cdd:cd08382   48 WNEHFDLTVGPS-SIITIQVF---DQKKFKKKDQgFLGCVRIRANAV 90
RasGAP_IQGAP3 cd12207
Ras-GTPase Activating Domain of IQ motif containing GTPase activating protein 3; This family ...
602-681 3.96e-04

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  Cd Length: 350  Bit Score: 44.43  E-value: 3.96e-04
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18859879  602 IFLRFLCPAILSPSLFNITSelPSARAT------RNLTLVAKTLQTLANFTRFQGKENFMEFLNDFLEQEAARMQQFLEI 675
Cdd:cd12207  189 LYYRFMNPAVVAPDGFDIVD--CSAGGAlqpeqrRMLGSVAKVLQHAAANKHFQGDSEHLQALNQYLEETHVKFRKFILQ 266

                 ....*.
gi 18859879  676 ISTRPE 681
Cdd:cd12207  267 ACCVPE 272
PH pfam00169
PH domain; PH stands for pleckstrin homology.
203-267 1.28e-03

PH domain; PH stands for pleckstrin homology.


Pssm-ID: 306640  Cd Length: 105  Bit Score: 40.24  E-value: 1.28e-03
                           10        20        30        40        50        60
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 18859879    203 SSHAVMSTIDLSctGAVGVAPVHQSVLGRRHCFQVRGGPRGER---YYSCGSRQERDLWIYSLRKSIA 267
Cdd:pfam00169   40 KSKEPKGSISLS--GCEVVEVVAPDSPKRKFCFELRTGERTGGrtyLLQAESEEERKDWIKAIQSAIR 105
 
Blast search parameters
Data Source: Precalculated data, version = cdd.v.3.16
Preset Options:Database: CDSEARCH/cdd   Low complexity filter: no  Composition Based Adjustment: yes   E-value threshold: 0.01

References:

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