NCBI Home Page NCBI Site Search page NCBI Guide that lists and describes the NCBI resources
Conserved domains on  [gi|94967023|ref|NP_115941|]
View 

disabled homolog 2-interacting protein isoform 1 [Homo sapiens]

Protein Classification

Ras GTPase-activating protein( domain architecture ID 11598912)

Ras GTPase-activating protein similar to Caenorhabditis elegans Ras GTPase-activating protein gap-2 that acts as a negative regulator of LET-60 Ras

Graphical summary

 Zoom to residue level

show extra options »

Show site features     Horizontal zoom: ×

List of domain hits

 Name Accession Description Interval E-value
DUF3498 pfam12004
Domain of unknown function (DUF3498); This presumed domain is functionally uncharacterized. ...
 618-1129 0e+00

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


:

Pssm-ID: 463427 [Multi-domain]  Cd Length: 511  Bit Score: 673.78  E-value: 0e+00
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94967023    618 LRDVHTALSTPGSGQLPG--TNDLASTPGSGSSSISAGLQKMVIENDLsGLIDFTRLPSPTPENKDLFFVTRSSGVQPSP 695
Cdd:pfam12004    1 LRDITTALTNPTPIQQQLrrFSEHSSSPPVPGRSISSGLQKMFEDPDD-GLSDFTRLPSPTPENKDLFFVTRPPLLQPSP 79

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94967023    696 ARSSSYSEANEPDLQMANGGKSLSMVDLQDARTLDGEAgSPAGPDVLPTDGQAAAAQLVAG---WPARATPVNLAGLATV 772
Cdd:pfam12004   80 ARSSSYSDANEPDQQLPNGNKSLSMVDLQDSRSLQGSP-SPPLHDAPLNLSQAGSQASVGLrpaWAARTSQGNPQSAPQV 158

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94967023    773 RRAGQTPTTPGTSEgapgrPQLLAPLSFQNPVYQMAAGLPLSPRGLG--DSGSEGHSSLSSHSNSEELAAAAK----LGS 846
Cdd:pfam12004  159 RRPLQTPVTQGTRP-----QQLLAPLSFQNPVYHMAAGLPVSPRGLGspDSSSETHSSFSSHSNSEDLSSAAAnkksGPS 233

                          250       260       270       280       290       300       310       320
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94967023    847 FSTAAEELARRPGELARRQMSLTEKGGQPTVPRQNSAGPQRRIDQPPPPPPPPPPAPRGRtppNLLSTLQYPRPSSGTLA 926
Cdd:pfam12004  234 NSSYSEDFARRSTEFTRRQLSLTELQHQPAVPRQNSAGPQRRIDQQGLGGPPLTRGRTPP---SLLNSASYPRPSSGSLM 310

                          330       340       350       360       370       380       390       400
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94967023    927 SASPDWvgPSTRLRQQSSSSKGDSPELKPRAVHKQGPSPVSPNALD---RTAAWLLTMNAQLLEDEGLGPDpphrdrlrS 1003
Cdd:pfam12004  311 SSSPDW--PPARLRQQSSSSKGDSPETKQRTQHQQVPSPVNPSTLSpveRTAAWVLNMNGQYEEEESSGPE--------S 380

                          410       420       430       440       450       460       470       480
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94967023   1004 KDELSQAEK---DLAVLQDKLRISTKKLEEYETLFKCQEETTQKLVLEYQARLEEGEERLRRQQEDKDIQMKGIISRLMS 1080
Cdd:pfam12004  381 REELKQAEKyeqEISKLKERLRVSNRKLEEYERRLLAQEEQTQKLLLEYQARLEDSEERLRRQQEEKDSQMKSIISRLMA 460

                          490       500       510       520
                   ....*....|....*....|....*....|....*....|....*....
gi 94967023   1081 VEEELKKDHAEMQAAVDSKQKIIDAQEKRIASLDAANARLMSALTQLKE 1129
Cdd:pfam12004  461 VEEELKKDHAEMQAVIDSKQKIIDAQEKRIASLDAANARLMSALTQLKE 509
RasGAP_DAB2IP cd05136
Ras-GTPase Activating Domain of DAB2IP and similar proteins; The DAB2IP family of Ras ...
 305-628 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: 613.82  E-value: 0e+00
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94967023  305 RYQTITILPMEMYKEFAEHITNHYLGLCAALEPILSAKTKEEMASALVHILQSTGKVKDFLTDLMMSEVDRCgDNEHLIF 384
Cdd:cd05136    1 RYQSVDILPLEVYKEFLEYLTNNYLDLCEVLEPVLSVKAKEELATALVHILQSTGKAKEFLTDLVMAEVDRL-DDEHLIF 79

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94967023  385 RENTLATKAIEEYLKLVGQKYLQDALGEFIKALYESDENCEVDPSKCSA-ADLPEHQGNLKMCCELAFCKIINSYCVFPR 463
Cdd:cd05136   80 RGNTLATKAMEAYLKLVGQKYLQETLGEFIRALYESEEDCEVDPSKCPPsASLSRNQANLRRSVELAWCKILSSHCVFPR 159

                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94967023  464 ELKEVFASWRQECSSRGRPDISERLISASLFLRFLCPAIMSPSLFNLLQEYPDDRTARTLTLIAKVTQNLANFAKFGSKE 543
Cdd:cd05136  160 ELREVFSSWRERLEERGREDIADRLISASLFLRFLCPAILSPSLFNLTQEYPSERAARNLTLIAKVIQNLANFTRFGGKE 239

                        250       260       270       280       290       300       310       320
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94967023  544 EYMSFMNQFLEHEWTNMQRFLLEISNPETLSNTAGFEGYIDLGRELSSLHSLLWEAVSQLEQSIVSKLGPLPRILRDVHT 623
Cdd:cd05136  240 EYMEFMNDFVEQEWPNMKQFLQEISSPSPSSNSSDFDGYIDLGRELSLLHSLLVEIISKLNQTTLDKLGPLPRILNDITE 319


                 ....*
gi 94967023  624 ALSTP 628
Cdd:cd05136  320 ALRNP 324
PH_DAB2IP cd13376
DOC-2/Disabled homolog 2-interacting protein Pleckstrin homology (PH) domain; DAB2IP (also ...
 47-233 3.14e-116

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: 357.09  E-value: 3.14e-116
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94967023   47 VTGFLSRRLKGSIKRTKSQPKLDRNHSFRHILPGFRSAaaaaaDNERSHLMPRLKESRSHESLLSPSSAVEALDLSMEEE 126
Cdd:cd13376    1 VTGFLSRRLKGSIKRTKSQPKLDRNSSFRHILPGFRSV-----DNERSHLMPRLKESRSHESLLSPSSAVEALDLSMEEE 75

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94967023  127 VVIKPVHSSILGQDYCFEVTTSSGSKCFSCRSAAERDKWMENLRRAVHPNKDNSRRVEHILKLWVIEAKDLPAKKKYLCE 206
Cdd:cd13376   76 VVIKPVHSSILGQDYCFEVTTSSGSKCFSCRSAAERDKWMENLRRAVHPNKDNSRRVENMLKLWIIEAKDLPAKKKYLCE 155

                        170       180
                 ....*....|....*....|....*..
gi 94967023  207 LCLDDVLYARTTGKLKTDNVFWGEHFE 233
Cdd:cd13376  156 LCLDDVLYARTTCKLKTDNVFWGEHFE 182
C2_SynGAP_like cd04013
C2 domain present in Ras GTPase activating protein (GAP) family; SynGAP, GAP1, RasGAP, and ...
 175-314 1.63e-78

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


:

Pssm-ID: 175980 [Multi-domain]  Cd Length: 146  Bit Score: 253.77  E-value: 1.63e-78
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94967023  175 PNKDNSRRVEHILKLWVIEAKDLPAKKKYLCELCLDDVLYARTTGKLKTDNVFWGEHFEFHNLPPLRTVTVHLYRETDKK 254
Cdd:cd04013    1 PNRDNSRRTENSLKLWIIEAKGLPPKKRYYCELCLDKTLYARTTSKLKTDTLFWGEHFEFSNLPPVSVITVNLYRESDKK 80

                         90       100       110       120       130       140
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 94967023  255 KKKERNSYLGLVSLPAASVAGRQFVEKWYPVVTPNP------KGGKGPGPMIRIKARYQTITILPM 314
Cdd:cd04013   81 KKKDKSQLIGTVNIPVTDVSSRQFVEKWYPVSTPKGngksggKEGKGESPSIRIKARYQSTRVLPL 146
 
Name Accession Description Interval E-value
DUF3498 pfam12004
Domain of unknown function (DUF3498); This presumed domain is functionally uncharacterized. ...
 618-1129 0e+00

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


Pssm-ID: 463427 [Multi-domain]  Cd Length: 511  Bit Score: 673.78  E-value: 0e+00
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94967023    618 LRDVHTALSTPGSGQLPG--TNDLASTPGSGSSSISAGLQKMVIENDLsGLIDFTRLPSPTPENKDLFFVTRSSGVQPSP 695
Cdd:pfam12004    1 LRDITTALTNPTPIQQQLrrFSEHSSSPPVPGRSISSGLQKMFEDPDD-GLSDFTRLPSPTPENKDLFFVTRPPLLQPSP 79

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94967023    696 ARSSSYSEANEPDLQMANGGKSLSMVDLQDARTLDGEAgSPAGPDVLPTDGQAAAAQLVAG---WPARATPVNLAGLATV 772
Cdd:pfam12004   80 ARSSSYSDANEPDQQLPNGNKSLSMVDLQDSRSLQGSP-SPPLHDAPLNLSQAGSQASVGLrpaWAARTSQGNPQSAPQV 158

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94967023    773 RRAGQTPTTPGTSEgapgrPQLLAPLSFQNPVYQMAAGLPLSPRGLG--DSGSEGHSSLSSHSNSEELAAAAK----LGS 846
Cdd:pfam12004  159 RRPLQTPVTQGTRP-----QQLLAPLSFQNPVYHMAAGLPVSPRGLGspDSSSETHSSFSSHSNSEDLSSAAAnkksGPS 233

                          250       260       270       280       290       300       310       320
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94967023    847 FSTAAEELARRPGELARRQMSLTEKGGQPTVPRQNSAGPQRRIDQPPPPPPPPPPAPRGRtppNLLSTLQYPRPSSGTLA 926
Cdd:pfam12004  234 NSSYSEDFARRSTEFTRRQLSLTELQHQPAVPRQNSAGPQRRIDQQGLGGPPLTRGRTPP---SLLNSASYPRPSSGSLM 310

                          330       340       350       360       370       380       390       400
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94967023    927 SASPDWvgPSTRLRQQSSSSKGDSPELKPRAVHKQGPSPVSPNALD---RTAAWLLTMNAQLLEDEGLGPDpphrdrlrS 1003
Cdd:pfam12004  311 SSSPDW--PPARLRQQSSSSKGDSPETKQRTQHQQVPSPVNPSTLSpveRTAAWVLNMNGQYEEEESSGPE--------S 380

                          410       420       430       440       450       460       470       480
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94967023   1004 KDELSQAEK---DLAVLQDKLRISTKKLEEYETLFKCQEETTQKLVLEYQARLEEGEERLRRQQEDKDIQMKGIISRLMS 1080
Cdd:pfam12004  381 REELKQAEKyeqEISKLKERLRVSNRKLEEYERRLLAQEEQTQKLLLEYQARLEDSEERLRRQQEEKDSQMKSIISRLMA 460

                          490       500       510       520
                   ....*....|....*....|....*....|....*....|....*....
gi 94967023   1081 VEEELKKDHAEMQAAVDSKQKIIDAQEKRIASLDAANARLMSALTQLKE 1129
Cdd:pfam12004  461 VEEELKKDHAEMQAVIDSKQKIIDAQEKRIASLDAANARLMSALTQLKE 509
RasGAP_DAB2IP cd05136
Ras-GTPase Activating Domain of DAB2IP and similar proteins; The DAB2IP family of Ras ...
 305-628 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: 613.82  E-value: 0e+00
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94967023  305 RYQTITILPMEMYKEFAEHITNHYLGLCAALEPILSAKTKEEMASALVHILQSTGKVKDFLTDLMMSEVDRCgDNEHLIF 384
Cdd:cd05136    1 RYQSVDILPLEVYKEFLEYLTNNYLDLCEVLEPVLSVKAKEELATALVHILQSTGKAKEFLTDLVMAEVDRL-DDEHLIF 79

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94967023  385 RENTLATKAIEEYLKLVGQKYLQDALGEFIKALYESDENCEVDPSKCSA-ADLPEHQGNLKMCCELAFCKIINSYCVFPR 463
Cdd:cd05136   80 RGNTLATKAMEAYLKLVGQKYLQETLGEFIRALYESEEDCEVDPSKCPPsASLSRNQANLRRSVELAWCKILSSHCVFPR 159

                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94967023  464 ELKEVFASWRQECSSRGRPDISERLISASLFLRFLCPAIMSPSLFNLLQEYPDDRTARTLTLIAKVTQNLANFAKFGSKE 543
Cdd:cd05136  160 ELREVFSSWRERLEERGREDIADRLISASLFLRFLCPAILSPSLFNLTQEYPSERAARNLTLIAKVIQNLANFTRFGGKE 239

                        250       260       270       280       290       300       310       320
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94967023  544 EYMSFMNQFLEHEWTNMQRFLLEISNPETLSNTAGFEGYIDLGRELSSLHSLLWEAVSQLEQSIVSKLGPLPRILRDVHT 623
Cdd:cd05136  240 EYMEFMNDFVEQEWPNMKQFLQEISSPSPSSNSSDFDGYIDLGRELSLLHSLLVEIISKLNQTTLDKLGPLPRILNDITE 319


                 ....*
gi 94967023  624 ALSTP 628
Cdd:cd05136  320 ALRNP 324
PH_DAB2IP cd13376
DOC-2/Disabled homolog 2-interacting protein Pleckstrin homology (PH) domain; DAB2IP (also ...
 47-233 3.14e-116

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: 357.09  E-value: 3.14e-116
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94967023   47 VTGFLSRRLKGSIKRTKSQPKLDRNHSFRHILPGFRSAaaaaaDNERSHLMPRLKESRSHESLLSPSSAVEALDLSMEEE 126
Cdd:cd13376    1 VTGFLSRRLKGSIKRTKSQPKLDRNSSFRHILPGFRSV-----DNERSHLMPRLKESRSHESLLSPSSAVEALDLSMEEE 75

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94967023  127 VVIKPVHSSILGQDYCFEVTTSSGSKCFSCRSAAERDKWMENLRRAVHPNKDNSRRVEHILKLWVIEAKDLPAKKKYLCE 206
Cdd:cd13376   76 VVIKPVHSSILGQDYCFEVTTSSGSKCFSCRSAAERDKWMENLRRAVHPNKDNSRRVENMLKLWIIEAKDLPAKKKYLCE 155

                        170       180
                 ....*....|....*....|....*..
gi 94967023  207 LCLDDVLYARTTGKLKTDNVFWGEHFE 233
Cdd:cd13376  156 LCLDDVLYARTTCKLKTDNVFWGEHFE 182
RasGAP smart00323
GTPase-activator protein for Ras-like GTPases; All alpha-helical domain that accelerates the ...
 300-621 2.25e-112

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: 353.15  E-value: 2.25e-112
                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94967023     300 IRIKARYQTITILPMEMYKEFAEHITNHYLG-LCAALEPILSAKTKEEMASALVHILQSTGKVKDFLTDLMMSEVDRCgD 378
Cdd:smart00323    9 LRLKTVYTTDFILPSEYYEELLELLLFSLDLsLASALSEVCSGLDKDELATKLVRLFLRRGRGHPFLRALIDPEVERT-D 87

                            90       100       110       120       130       140       150       160
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94967023     379 NEHLIFRENTLATKAIEEYLKLVGQKYLQDALGEFIKALYESDENCEVDPSKCSAADLPEHQGNLKMCCELAFCKIINSY 458
Cdd:smart00323   88 DPNTIFRGNSLATKSMEVYMKLVGNQYLHTTLKPVLKKIVESKKSCEVDPAKLEGEDLETNLENLLQYVERLFDAIINSS 167

                           170       180       190       200       210       220       230       240
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94967023     459 CVFPRELKEVFASWRQECSSR-GRPDISERLISASLFLRFLCPAIMSPSLFNLLQEYPDDRTARTLTLIAKVTQNLANFA 537
Cdd:smart00323  168 DRLPYGLRDICKQLRQAAEKRfPDADVIYKAVSSFVFLRFFCPAIVSPKLFNLVDEHPDPTTRRTLTLIAKVLQNLANLS 247

                           250       260       270       280       290       300       310       320
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94967023     538 KFGSKEEYMSFMNQFLEHEWTNMQRFLLEISNPETLSNTAGFEGYIDLGRELSSLHSLLWEAVSQL-----EQSIVSKLG 612
Cdd:smart00323  248 EFGSKEPWMEPLNDFLLSHKDRVKDFLDELSSVPEILVDKVSDSTTISGRELSLLHSLLLENGDALkrelnNEDPLGKLL 327


                    ....*....
gi 94967023     613 PLPRILRDV 621
Cdd:smart00323  328 FKLRYFGLT 336
C2_SynGAP_like cd04013
C2 domain present in Ras GTPase activating protein (GAP) family; SynGAP, GAP1, RasGAP, and ...
 175-314 1.63e-78

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


Pssm-ID: 175980 [Multi-domain]  Cd Length: 146  Bit Score: 253.77  E-value: 1.63e-78
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94967023  175 PNKDNSRRVEHILKLWVIEAKDLPAKKKYLCELCLDDVLYARTTGKLKTDNVFWGEHFEFHNLPPLRTVTVHLYRETDKK 254
Cdd:cd04013    1 PNRDNSRRTENSLKLWIIEAKGLPPKKRYYCELCLDKTLYARTTSKLKTDTLFWGEHFEFSNLPPVSVITVNLYRESDKK 80

                         90       100       110       120       130       140
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 94967023  255 KKKERNSYLGLVSLPAASVAGRQFVEKWYPVVTPNP------KGGKGPGPMIRIKARYQTITILPM 314
Cdd:cd04013   81 KKKDKSQLIGTVNIPVTDVSSRQFVEKWYPVSTPKGngksggKEGKGESPSIRIKARYQSTRVLPL 146
RasGAP pfam00616
GTPase-activator protein for Ras-like GTPase; All alpha-helical domain that accelerates the ...
 364-535 4.62e-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: 459871  Cd Length: 207  Bit Score: 115.85  E-value: 4.62e-29
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94967023    364 FLTDLMMSEVDRCgDNEHLIFRENTLATKAIEEYLKL-VGQKYLQDALGEFIKALYESDE-NCEVDPSK----------- 430
Cdd:pfam00616    1 LISELIEEEIESS-DNPNDLLRGNSLVSKLLETYNRRpRGQEYLKKVLGPLVRKIIEDEDlDLESDPRKiyeslinqeel 79

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94967023    431 -------------CSAADLPE-------HQGNLKMCCELAFCKIINSYCVFPREL----KEVFASWRQECssrgrPDISE 486
Cdd:pfam00616   80 ktgrsdlprdvspEEAIEDPEvrqifedNLQKLRELADEFLDAIYSSLNQLPYGIryicKQLYELLEEKF-----PDASE 154

                          170       180       190       200       210
                   ....*....|....*....|....*....|....*....|....*....|...
gi 94967023    487 R----LISASLFLRFLCPAIMSPSLFNLLQEYPDDRTARTLTLIAKVTQNLAN 535
Cdd:pfam00616  155 EeilnAIGGFLFLRFFCPAIVNPDLFGLVDHQISPKQRRNLTLIAKVLQNLAN 207
C2 pfam00168
C2 domain;
185-285 1.72e-08

C2 domain;


Pssm-ID: 425499 [Multi-domain]  Cd Length: 104  Bit Score: 53.48  E-value: 1.72e-08
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94967023    185 HILKLWVIEAKDLPAKKK------YlCELCLDDVLY-ARTTGKLKTDNVFWGEHFEFH-NLPPLRTVTVHLYretDKKKK 256
Cdd:pfam00168    1 GRLTVTVIEAKNLPPKDGngtsdpY-VKVYLLDGKQkKKTKVVKNTLNPVWNETFTFSvPDPENAVLEIEVY---DYDRF 76

                           90       100
                   ....*....|....*....|....*....
gi 94967023    257 KeRNSYLGLVSLPAASVAGRQFVEKWYPV 285
Cdd:pfam00168   77 G-RDDFIGEVRIPLSELDSGEGLDGWYPL 104
C2 smart00239
Protein kinase C conserved region 2 (CalB); Ca2+-binding motif present in phospholipases, ...
 186-282 1.85e-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 [Multi-domain]  Cd Length: 101  Bit Score: 53.26  E-value: 1.85e-08
                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94967023     186 ILKLWVIEAKDLPAKKKYL-----CELCLDDVLY--ARTTGKLKTDNVFWGEHFEFH-NLPPLRTVTVHLYretDKKKKK 257
Cdd:smart00239    1 TLTVKIISARNLPPKDKGGksdpyVKVSLDGDPKekKKTKVVKNTLNPVWNETFEFEvPPPELAELEIEVY---DKDRFG 77

                            90       100
                    ....*....|....*....|....*
gi 94967023     258 eRNSYLGLVSLPAASVAGRQFVEKW 282
Cdd:smart00239   78 -RDDFIGQVTIPLSDLLLGGRHEKL 101
PH smart00233
Pleckstrin homology domain; Domain commonly found in eukaryotic signalling proteins. The ...
 121-174 2.02e-06

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


Pssm-ID: 214574 [Multi-domain]  Cd Length: 102  Bit Score: 47.54  E-value: 2.02e-06
                            10        20        30        40        50
                    ....*....|....*....|....*....|....*....|....*....|....*
gi 94967023     121 LSMEEEVVIKPVHSSILGQDYCFEVTTSSG-SKCFSCRSAAERDKWMENLRRAVH 174
Cdd:smart00233   48 IDLSGCTVREAPDPDSSKKPHCFEIKTSDRkTLLLQAESEEEREKWVEALRKAIA 102
SMC_prok_B TIGR02168
chromosome segregation protein SMC, common bacterial type; SMC (structural maintenance of ...
 992-1132 1.31e-05

chromosome segregation protein SMC, common bacterial type; SMC (structural maintenance of chromosomes) proteins bind DNA and act in organizing and segregating chromosomes for partition. SMC proteins are found in bacteria, archaea, and eukaryotes. This family represents the SMC protein of most bacteria. The smc gene is often associated with scpB (TIGR00281) and scpA genes, where scp stands for segregation and condensation protein. SMC was shown (in Caulobacter crescentus) to be induced early in S phase but present and bound to DNA throughout the cell cycle. [Cellular processes, Cell division, DNA metabolism, Chromosome-associated proteins]


Pssm-ID: 274008 [Multi-domain]  Cd Length: 1179  Bit Score: 49.67  E-value: 1.31e-05
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94967023    992 GPDPPHRDRLRSKDELSQAEKDLAVLQDKLRISTKKLEEYETLF-----------KCQEETTQKLVLEYQ--ARLEEGEE 1058
Cdd:TIGR02168  664 GSAKTNSSILERRREIEELEEKIEELEEKIAELEKALAELRKELeeleeeleqlrKELEELSRQISALRKdlARLEAEVE 743

                           90       100       110       120       130       140       150
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 94967023   1059 RLRRQQEDKDIQMKGIISRLMSVEEELKKDHAEMQAAVDSKQKI---IDAQEKRIASLDAANARLMSALTQLKESMH 1132
Cdd:TIGR02168  744 QLEERIAQLSKELTELEAEIEELEERLEEAEEELAEAEAEIEELeaqIEQLKEELKALREALDELRAELTLLNEEAA 820
PRK03918 PRK03918
DNA double-strand break repair ATPase Rad50;
1004-1129 4.46e-05

DNA double-strand break repair ATPase Rad50;


Pssm-ID: 235175 [Multi-domain]  Cd Length: 880  Bit Score: 47.75  E-value: 4.46e-05
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94967023  1004 KDELSQAEKDLAVLQDKLRISTKKLEEYETLFKCQEETTQKLVlEYQARLEEGEERLRRQQEDKDI--QMKGIISRLMSV 1081
Cdd:PRK03918  306 LDELREIEKRLSRLEEEINGIEERIKELEEKEERLEELKKKLK-ELEKRLEELEERHELYEEAKAKkeELERLKKRLTGL 384

                          90       100       110       120       130
                  ....*....|....*....|....*....|....*....|....*....|..
gi 94967023  1082 E-EELKKdhaEMQAAVDSKQKIIDAQEK---RIASLDAANARLMSALTQLKE 1129
Cdd:PRK03918  385 TpEKLEK---ELEELEKAKEEIEEEISKitaRIGELKKEIKELKKAIEELKK 433
Smc COG1196
Chromosome segregation ATPase Smc [Cell cycle control, cell division, chromosome partitioning]; ...
 1004-1129 6.14e-05

Chromosome segregation ATPase Smc [Cell cycle control, cell division, chromosome partitioning];


Pssm-ID: 440809 [Multi-domain]  Cd Length: 983  Bit Score: 47.24  E-value: 6.14e-05
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94967023 1004 KDELSQAEKDLAVLQDKLRISTKKLEEYETLFKCQEETTQKLVLEyQARLEEGEERLRRQQEDKDIQMKGIISRLMSVEE 1083
Cdd:COG1196  273 RLELEELELELEEAQAEEYELLAELARLEQDIARLEERRRELEER-LEELEEELAELEEELEELEEELEELEEELEEAEE 351

                         90       100       110       120
                 ....*....|....*....|....*....|....*....|....*.
gi 94967023 1084 ELKKDHAEMQAAVDSKQKIIDAQEKRIASLDAANARLMSALTQLKE 1129
Cdd:COG1196  352 ELEEAEAELAEAEEALLEAEAELAEAEEELEELAEELLEALRAAAE 397
rad4 TIGR00605
DNA repair protein rad4; All proteins in this family for which functions are known are ...
 15-194 7.44e-03

DNA repair protein rad4; All proteins in this family for which functions are known are involved in targeting nucleotide excision repair to specific regions of the genome.This family is based on the phylogenomic analysis of JA Eisen (1999, Ph.D. Thesis, Stanford University). [DNA metabolism, DNA replication, recombination, and repair]


Pssm-ID: 273170 [Multi-domain]  Cd Length: 713  Bit Score: 40.25  E-value: 7.44e-03
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94967023     15 SPQERPGSRRSLPGSLSEKSPSmEPSAATPFRVTGFLSRRLKGSI-KRTKSQPK-LDRNHSFRH----ILPGFRSAAAaa 88
Cdd:TIGR00605  271 SILENLNVPTRLVFSDFLLSVS-KGHNDPEISSEGFVPKLSACNAnQRLIMSCEsADRTSRFRMkkdpSLPGFSAYSD-- 347

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94967023     89 aDNERSHLMPRLKESRSHESLLSPSSAVEALDLSMEEEVVIKPVHSSILGQDY-CFEVTTSSGSKCFscrsAAERDKWME 167
Cdd:TIGR00605  348 -MDKSPIFTCEEGDKFIDRWITYVDFWVEVFIEQEEKWVCVDAVHSGVVPKGVtCFEPATLMMTYVF----AYDRDGYVK 422

                          170       180
                   ....*....|....*....|....*..
gi 94967023    168 NLRRAVHPNKDNSRRVEHILKLWVIEA 194
Cdd:TIGR00605  423 DVTRRYCDQWSTKVRKRRVEKADFGET 449
 
Name Accession Description Interval E-value
DUF3498 pfam12004
Domain of unknown function (DUF3498); This presumed domain is functionally uncharacterized. ...
 618-1129 0e+00

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


Pssm-ID: 463427 [Multi-domain]  Cd Length: 511  Bit Score: 673.78  E-value: 0e+00
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94967023    618 LRDVHTALSTPGSGQLPG--TNDLASTPGSGSSSISAGLQKMVIENDLsGLIDFTRLPSPTPENKDLFFVTRSSGVQPSP 695
Cdd:pfam12004    1 LRDITTALTNPTPIQQQLrrFSEHSSSPPVPGRSISSGLQKMFEDPDD-GLSDFTRLPSPTPENKDLFFVTRPPLLQPSP 79

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94967023    696 ARSSSYSEANEPDLQMANGGKSLSMVDLQDARTLDGEAgSPAGPDVLPTDGQAAAAQLVAG---WPARATPVNLAGLATV 772
Cdd:pfam12004   80 ARSSSYSDANEPDQQLPNGNKSLSMVDLQDSRSLQGSP-SPPLHDAPLNLSQAGSQASVGLrpaWAARTSQGNPQSAPQV 158

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94967023    773 RRAGQTPTTPGTSEgapgrPQLLAPLSFQNPVYQMAAGLPLSPRGLG--DSGSEGHSSLSSHSNSEELAAAAK----LGS 846
Cdd:pfam12004  159 RRPLQTPVTQGTRP-----QQLLAPLSFQNPVYHMAAGLPVSPRGLGspDSSSETHSSFSSHSNSEDLSSAAAnkksGPS 233

                          250       260       270       280       290       300       310       320
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94967023    847 FSTAAEELARRPGELARRQMSLTEKGGQPTVPRQNSAGPQRRIDQPPPPPPPPPPAPRGRtppNLLSTLQYPRPSSGTLA 926
Cdd:pfam12004  234 NSSYSEDFARRSTEFTRRQLSLTELQHQPAVPRQNSAGPQRRIDQQGLGGPPLTRGRTPP---SLLNSASYPRPSSGSLM 310

                          330       340       350       360       370       380       390       400
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94967023    927 SASPDWvgPSTRLRQQSSSSKGDSPELKPRAVHKQGPSPVSPNALD---RTAAWLLTMNAQLLEDEGLGPDpphrdrlrS 1003
Cdd:pfam12004  311 SSSPDW--PPARLRQQSSSSKGDSPETKQRTQHQQVPSPVNPSTLSpveRTAAWVLNMNGQYEEEESSGPE--------S 380

                          410       420       430       440       450       460       470       480
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94967023   1004 KDELSQAEK---DLAVLQDKLRISTKKLEEYETLFKCQEETTQKLVLEYQARLEEGEERLRRQQEDKDIQMKGIISRLMS 1080
Cdd:pfam12004  381 REELKQAEKyeqEISKLKERLRVSNRKLEEYERRLLAQEEQTQKLLLEYQARLEDSEERLRRQQEEKDSQMKSIISRLMA 460

                          490       500       510       520
                   ....*....|....*....|....*....|....*....|....*....
gi 94967023   1081 VEEELKKDHAEMQAAVDSKQKIIDAQEKRIASLDAANARLMSALTQLKE 1129
Cdd:pfam12004  461 VEEELKKDHAEMQAVIDSKQKIIDAQEKRIASLDAANARLMSALTQLKE 509
RasGAP_DAB2IP cd05136
Ras-GTPase Activating Domain of DAB2IP and similar proteins; The DAB2IP family of Ras ...
 305-628 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: 613.82  E-value: 0e+00
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94967023  305 RYQTITILPMEMYKEFAEHITNHYLGLCAALEPILSAKTKEEMASALVHILQSTGKVKDFLTDLMMSEVDRCgDNEHLIF 384
Cdd:cd05136    1 RYQSVDILPLEVYKEFLEYLTNNYLDLCEVLEPVLSVKAKEELATALVHILQSTGKAKEFLTDLVMAEVDRL-DDEHLIF 79

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94967023  385 RENTLATKAIEEYLKLVGQKYLQDALGEFIKALYESDENCEVDPSKCSA-ADLPEHQGNLKMCCELAFCKIINSYCVFPR 463
Cdd:cd05136   80 RGNTLATKAMEAYLKLVGQKYLQETLGEFIRALYESEEDCEVDPSKCPPsASLSRNQANLRRSVELAWCKILSSHCVFPR 159

                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94967023  464 ELKEVFASWRQECSSRGRPDISERLISASLFLRFLCPAIMSPSLFNLLQEYPDDRTARTLTLIAKVTQNLANFAKFGSKE 543
Cdd:cd05136  160 ELREVFSSWRERLEERGREDIADRLISASLFLRFLCPAILSPSLFNLTQEYPSERAARNLTLIAKVIQNLANFTRFGGKE 239

                        250       260       270       280       290       300       310       320
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94967023  544 EYMSFMNQFLEHEWTNMQRFLLEISNPETLSNTAGFEGYIDLGRELSSLHSLLWEAVSQLEQSIVSKLGPLPRILRDVHT 623
Cdd:cd05136  240 EYMEFMNDFVEQEWPNMKQFLQEISSPSPSSNSSDFDGYIDLGRELSLLHSLLVEIISKLNQTTLDKLGPLPRILNDITE 319


                 ....*
gi 94967023  624 ALSTP 628
Cdd:cd05136  320 ALRNP 324
PH_DAB2IP cd13376
DOC-2/Disabled homolog 2-interacting protein Pleckstrin homology (PH) domain; DAB2IP (also ...
 47-233 3.14e-116

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: 357.09  E-value: 3.14e-116
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94967023   47 VTGFLSRRLKGSIKRTKSQPKLDRNHSFRHILPGFRSAaaaaaDNERSHLMPRLKESRSHESLLSPSSAVEALDLSMEEE 126
Cdd:cd13376    1 VTGFLSRRLKGSIKRTKSQPKLDRNSSFRHILPGFRSV-----DNERSHLMPRLKESRSHESLLSPSSAVEALDLSMEEE 75

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94967023  127 VVIKPVHSSILGQDYCFEVTTSSGSKCFSCRSAAERDKWMENLRRAVHPNKDNSRRVEHILKLWVIEAKDLPAKKKYLCE 206
Cdd:cd13376   76 VVIKPVHSSILGQDYCFEVTTSSGSKCFSCRSAAERDKWMENLRRAVHPNKDNSRRVENMLKLWIIEAKDLPAKKKYLCE 155

                        170       180
                 ....*....|....*....|....*..
gi 94967023  207 LCLDDVLYARTTGKLKTDNVFWGEHFE 233
Cdd:cd13376  156 LCLDDVLYARTTCKLKTDNVFWGEHFE 182
RasGAP smart00323
GTPase-activator protein for Ras-like GTPases; All alpha-helical domain that accelerates the ...
 300-621 2.25e-112

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: 353.15  E-value: 2.25e-112
                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94967023     300 IRIKARYQTITILPMEMYKEFAEHITNHYLG-LCAALEPILSAKTKEEMASALVHILQSTGKVKDFLTDLMMSEVDRCgD 378
Cdd:smart00323    9 LRLKTVYTTDFILPSEYYEELLELLLFSLDLsLASALSEVCSGLDKDELATKLVRLFLRRGRGHPFLRALIDPEVERT-D 87

                            90       100       110       120       130       140       150       160
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94967023     379 NEHLIFRENTLATKAIEEYLKLVGQKYLQDALGEFIKALYESDENCEVDPSKCSAADLPEHQGNLKMCCELAFCKIINSY 458
Cdd:smart00323   88 DPNTIFRGNSLATKSMEVYMKLVGNQYLHTTLKPVLKKIVESKKSCEVDPAKLEGEDLETNLENLLQYVERLFDAIINSS 167

                           170       180       190       200       210       220       230       240
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94967023     459 CVFPRELKEVFASWRQECSSR-GRPDISERLISASLFLRFLCPAIMSPSLFNLLQEYPDDRTARTLTLIAKVTQNLANFA 537
Cdd:smart00323  168 DRLPYGLRDICKQLRQAAEKRfPDADVIYKAVSSFVFLRFFCPAIVSPKLFNLVDEHPDPTTRRTLTLIAKVLQNLANLS 247

                           250       260       270       280       290       300       310       320
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94967023     538 KFGSKEEYMSFMNQFLEHEWTNMQRFLLEISNPETLSNTAGFEGYIDLGRELSSLHSLLWEAVSQL-----EQSIVSKLG 612
Cdd:smart00323  248 EFGSKEPWMEPLNDFLLSHKDRVKDFLDELSSVPEILVDKVSDSTTISGRELSLLHSLLLENGDALkrelnNEDPLGKLL 327


                    ....*....
gi 94967023     613 PLPRILRDV 621
Cdd:smart00323  328 FKLRYFGLT 336
PH_SynGAP cd13375
Synaptic Ras-GTPase activating protein Pleckstrin homology (PH) domain; SynGAP is a member of ...
 42-233 1.40e-102

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: 320.88  E-value: 1.40e-102
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94967023   42 ATPFRVT-GFLSRRLKGSIKRTKSQPKLDRNHSFRHILPGFRSAaaaaaDNERSHLMPRLKESRSHESLLSPSSAVEALD 120
Cdd:cd13375    2 TAPFRPSqGFLSRRLKSSIKRTKSQPKLDRTSSFRQILPRFRSA-----DHDRARLMQSFKESHSHESLLSPSSAAEALD 76

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94967023  121 LSMEEEVVIKPVHSSILGQDYCFEVTTSSGSKCFSCRSAAERDKWMENLRRAVHPNKDNSRRVEHILKLWVIEAKDLPAK 200
Cdd:cd13375   77 LNLDEDSIIKPVHSSILGQEFCFEVTTASGTKCFACRSAAERDKWIENLQRAVKPNKDNSRRVDNVLKLWIIEARELPPK 156

                        170       180       190
                 ....*....|....*....|....*....|...
gi 94967023  201 KKYLCELCLDDVLYARTTGKLKTDNVFWGEHFE 233
Cdd:cd13375  157 KRYYCELCLDDMLYARTTSKPRTDTVFWGEHFE 189
C2_SynGAP_like cd04013
C2 domain present in Ras GTPase activating protein (GAP) family; SynGAP, GAP1, RasGAP, and ...
 175-314 1.63e-78

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


Pssm-ID: 175980 [Multi-domain]  Cd Length: 146  Bit Score: 253.77  E-value: 1.63e-78
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94967023  175 PNKDNSRRVEHILKLWVIEAKDLPAKKKYLCELCLDDVLYARTTGKLKTDNVFWGEHFEFHNLPPLRTVTVHLYRETDKK 254
Cdd:cd04013    1 PNRDNSRRTENSLKLWIIEAKGLPPKKRYYCELCLDKTLYARTTSKLKTDTLFWGEHFEFSNLPPVSVITVNLYRESDKK 80

                         90       100       110       120       130       140
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 94967023  255 KKKERNSYLGLVSLPAASVAGRQFVEKWYPVVTPNP------KGGKGPGPMIRIKARYQTITILPM 314
Cdd:cd04013   81 KKKDKSQLIGTVNIPVTDVSSRQFVEKWYPVSTPKGngksggKEGKGESPSIRIKARYQSTRVLPL 146
RasGAP cd04519
Ras GTPase Activating Domain; RasGAP functions as an enhancer of the hydrolysis of GTP that is ...
 317-569 4.24e-74

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


Pssm-ID: 213328  Cd Length: 256  Bit Score: 245.86  E-value: 4.24e-74
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94967023  317 YKEFAEHITNHYLGLCAALEPILSAKTKEEMASALVHILQSTGKVKDFLTDLMMSEVDRCgDNEHLIFRENTLATKAIEE 396
Cdd:cd04519    3 YRLLSLLLTESPLALLRELSQVLPVKDKEEVATALLRIFESRGLALEFLRYLVRSEVKNT-KNPNTLFRGNSLATKLLDQ 81

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94967023  397 YLKLVGQKYLQDALGEFIKALYESDENCEVDPSKCSAADLPEHQGNLKMCCELAFCKIINSYCVFPRELKEVFASWRQEC 476
Cdd:cd04519   82 YMKLVGQEYLKETLSPLIREILESKESCEIDTKLPVGEDLEENLENLLELVNKLVDRILSSLDRLPPELRYVFKILREFL 161

                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94967023  477 SSR--GRPDISERLISASLFLRFLCPAIMSPSLFNLLQEYPDDRTARTLTLIAKVTQNLANFAKFGSKEEYMSFMNQFLE 554
Cdd:cd04519  162 AERfpEEPDEAYQAVSGFLFLRFICPAIVSPELFGLVPDEPSEQARRNLTLISKVLQSLANGVEFGDKEPFMKPLNDFIK 241

                        250
                 ....*....|....*
gi 94967023  555 HEWTNMQRFLLEISN 569
Cdd:cd04519  242 SNKPKLKQFLDELSS 256
PH_nGAP cd13373
Neuronal growth-associated proteins Pleckstrin homology (PH) domain; nGAP (also called RASAL2 ...
 44-189 1.50e-61

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: 206.12  E-value: 1.50e-61
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94967023   44 PFRVTGFLSRRLKGSIKRTKSQPKLDRNHSFRhiLPGFRSAaaaaadNERSHLMPRLKESRSHESLLSPSSAVEALDLSM 123
Cdd:cd13373    1 PFKVSGFFSKRLKGSIKRTKSQSKLDRNTSFR--LPSLRSA------DDRSRGLPKLKESRSHESLLSPGSAVEALDLGR 72

                         90       100       110       120       130       140
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 94967023  124 EEEVVIKPVHSSILGQDYCFEVTTSSGSKCFSCRSAAERDKWMENLRRAVHPNKDNSRRVEHILKL 189
Cdd:cd13373   73 EEKVSVKPLHSSILGQDFCFEVTYSSGSKCFSCSSAAERDKWMENLRRTVQPNKDNCRRAENVLRL 138
PH_RasSynGAP-like cd13262
Synaptic Ras-GTPase activating protein family Pleckstrin homology (PH) domain; The RasSynGAP ...
 47-183 2.64e-59

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: 199.19  E-value: 2.64e-59
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94967023   47 VTGFLSRRLKGSIKRTKSQPKLDRNHSFRhiLPGFRSAaaaaadneRSHLMPRLKESRSHESLLSPSSAveALDLSMEEE 126
Cdd:cd13262    1 ASGFFSRRLKGPLKRTKSVTKLERKSSKR--LPRTRLA--------RAPAGPRLRGSRSHESLLSSSSA--ALDLSADED 68

                         90       100       110       120       130
                 ....*....|....*....|....*....|....*....|....*....|....*..
gi 94967023  127 VVIKPVHSSILGQDYCFEVTTSSGSKCFSCRSAAERDKWMENLRRAVHPNKDNSRRV 183
Cdd:cd13262   69 VVIRPLHSSILGRKHCFQVTTSEGTRCFSCRSAAERDRWIEDLRRAAQPNKDNCRRT 125
RasGAP_CLA2_BUD2 cd05137
Ras-GTPase Activating Domain of CLA2/BUD2; CLA2/BUD2 functions as a GTPase-activating protein ...
 303-554 2.35e-55

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


Pssm-ID: 213339 [Multi-domain]  Cd Length: 356  Bit Score: 196.63  E-value: 2.35e-55
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94967023  303 KARYQTITILPMEMYKEFAEHITNHYLGLCAALEPILSAKTKEEMASALVHILQSTGKVKDFLTDLMMSEVD-------- 374
Cdd:cd05137    1 KVRLDENVVLPSKNYKPLEELLHNFDLGLTLQIAELVPGDKLERLSEILLDIFQASGREDEWFMALVEDEIDgidkstsk 80

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94967023  375 -----RCGDNEH-LIFRENTLATKAIEEYLKLVGQKYLQDALGEFIKALYESDENCEVDPSKCSAA-------DLPEHQG 441
Cdd:cd05137   81 nkdmgKSSNNEAnLLFRGNSLLTKSLEKYMRRIGKEYLEKSIGDVIRKICEENKDCEVDPSRVKESdsiekeeDLEENWE 160

                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94967023  442 NLKMCCELAFCKIINSYCVFPRELKEVFASWRQECSSRGRPDISE-RL--ISASLFLRFLCPAIMSPSLFNLLQEYPDDR 518
Cdd:cd05137  161 NLISLTEEIWNSIYITSNDCPPELRKILKHIRAKVEDRYGDFLRTvTLnsVSGFLFLRFFCPAILNPKLFGLLKDHPRPR 240

                        250       260       270
                 ....*....|....*....|....*....|....*.
gi 94967023  519 TARTLTLIAKVTQNLANFAKFGSKEEYMSFMNQFLE 554
Cdd:cd05137  241 AQRTLTLIAKVLQNLANLTTFGQKEPWMEPMNEFLT 276
RasGAP_GAP1_like cd05128
Ras-GTPase Activating Domain of GAP1 and similar proteins; The GAP1 family of Ras ...
 330-570 4.13e-50

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


Pssm-ID: 213330  Cd Length: 269  Bit Score: 178.60  E-value: 4.13e-50
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94967023  330 GLCAALEPILSAKtKEEMASALVHILQSTGKVKDFLTDLMMSEVDRCGDnEHLIFRENTLATKAIEEYLKLVGQKYLQDA 409
Cdd:cd05128   22 SAVYLLEELVKVD-KDDVARPLVRIFLHHGQIVPLLRALASREISKTQD-PNTLFRGNSLASKCMDEFMKLVGMQYLHET 99

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94967023  410 LGEFIKALYESDENCEVDPSKCSAADLPE-HQGNLKMCCELAFCKIINSYCVFPRELKEVFASWRQECSSR--GRPDISE 486
Cdd:cd05128  100 LKPVIDEIFSEKKSCEIDPSKLKDGEVLEtNLANLRGYVERVFKAITSSARRCPTLMCEIFSDLRESAAQRfpDNEDVPY 179

                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94967023  487 RLISASLFLRFLCPAIMSPSLFNLLQEYPDDRTARTLTLIAKVTQNLANFAKFGS----KEEYMS-FMNQFL-EHEWTNM 560
Cdd:cd05128  180 TAVSGFIFLRFFAPAILNPKLFGLREEHPDPQTARTLTLISKTIQTLGNLGSSSSglgvKEAYMSpLYERFTdEQHVDAV 259

                        250
                 ....*....|
gi 94967023  561 QRFLLEISNP 570
Cdd:cd05128  260 KKFLDRISSV 269
RasGAP_Neurofibromin_like cd05392
Ras-GTPase Activating Domain of proteins similar to neurofibromin; Neurofibromin-like proteins ...
 313-609 1.62e-45

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: 166.69  E-value: 1.62e-45
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94967023  313 PMEMYKEFAEHITNHYLGLCAALEpILSAKTKEEMASALVHILQSTGKVKDFLTDLMMSEVDRCgDNEHLIFRENTLATK 392
Cdd:cd05392    2 KSEAYDELLELLIEDPQLLLAIAE-VCPSSEVDLLAQSLLNLFETRNRLLPLISWLIEDEISHT-SRAADLFRRNSVATR 79

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94967023  393 AIEEYLKLVGQKYLQDALGEFIKALYESDENCEVDPSKCSAADLPEHQGNLKMCCELAFCKIINSYCVFPRELKEVFASW 472
Cdd:cd05392   80 LLTLYAKSVGNKYLRKVLRPLLTEIVDNKDYFEVEKIKPDDENLEENADLLMKYAQMLLDSITDSVDQLPPSFRYICNTI 159

                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94967023  473 RQECSSRgRPDISERLISASLFLRFLCPAIMSPSLFNLLQEYPDDRTARTLTLIAKVTQNLANFAKFGSKEEYMSFMNQF 552
Cdd:cd05392  160 YESVSKK-FPDAALIAVGGFLFLRFICPAIVSPESENLLDPPPTPEARRSLILIAKVLQNIANGVLFSLKEPYLESLNEF 238

                        250       260       270       280       290
                 ....*....|....*....|....*....|....*....|....*....|....*..
gi 94967023  553 LEHEWTNMQRFLLEISNPETLSNTAGFEGYIDLGRELSSLHSLLWEAVSQLEQSIVS 609
Cdd:cd05392  239 LKKNSDRIQQFLSEVSTIPPTDPIFDESDEEPITADLRYLHKFLYLHFLEIRKEVLK 295
RasGAP_p120GAP cd05391
Ras-GTPase Activating Domain of p120; p120GAP is a negative regulator of Ras that stimulates ...
 311-618 3.09e-43

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


Pssm-ID: 213340  Cd Length: 328  Bit Score: 160.73  E-value: 3.09e-43
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94967023  311 ILPMEMYKEFAEHITNHYLGLCAALEPiLSAKTKEEMASALVHILQSTGKVKDFLTDLMMSEVDRcGDNEHLIFRENTLA 390
Cdd:cd05391    4 IMPEEEYSELKELILQKELHVVYALAH-VCGQDRTLLASILLRIFRHEKLESLLLRTLNDREISM-EDEATTLFRATTLA 81

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94967023  391 TKAIEEYLKLVGQKYLQDALGEFIKALYESDENCEVDPSKCSAADlpEHQGNLKMCCELAFC---KIINSYCVFPRELKE 467
Cdd:cd05391   82 STLMEQYMKATATPFVHHALKDTILKILESKQSCELNPSKLEKNE--DVNTNLEHLLNILSElveKIFMAAEILPPTLRY 159

                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94967023  468 VFaSWRQECSSRGRPD---ISERLISASLFLRFLCPAIMSPSLFNLLQEYPDDRTARTLTLIAKVTQNLANFAKFGSKEE 544
Cdd:cd05391  160 IY-GCLQKSVQQKWPTnttVRTRVVSGFVFLRLICPAILNPRMFNIISETPSPTAARTLTLVAKSLQNLANLVEFGAKEP 238

                        250       260       270       280       290       300       310
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 94967023  545 YMSFMNQFLEHEWTNMQRFLLEISN-PETLSNTAGFEGyiDLGRELSSLHSLLWEAVSQLeQSIVSKLGPLPRIL 618
Cdd:cd05391  239 YMEGVNPFIKKNKERMIMFLDELGNvPELPDTTEHSRT--DLSRDLAALHEICVAHSDEL-RTLSNERGALKKLL 310
RasGAP_RASA3 cd05134
Ras-GTPase Activating Domain of RASA3; RASA3 (or GAP1_IP4BP) is a member of the GAP1 family ...
 342-569 1.19e-38

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


Pssm-ID: 213336  Cd Length: 269  Bit Score: 145.55  E-value: 1.19e-38
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94967023  342 KTKEEMASALVHILQSTGKVKDFLTDLMMSEVDRCGDnEHLIFRENTLATKAIEEYLKLVGQKYLQDALGEFIKALYESD 421
Cdd:cd05134   33 REKQEAAIPLVRLFLHYGKIVPFISAIASAEVNRTQD-PNTIFRGNSLTSKCIDETMKLAGMHYLQVTLKPIIDEICQEH 111

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94967023  422 ENCEVDPSKCS-AADLPEHQGNLKMCCELAFCKIINSYCVFPRELKEVFASWRQECSSR--GRPDISERLISASLFLRFL 498
Cdd:cd05134  112 KPCEIDPVKLKdGENLENNRENLRQYVDRIFRVITKSGVSCPTVMCDIFFSLRESAAKRfqVDPDVRYTAVSSFIFLRFF 191

                        170       180       190       200       210       220       230
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 94967023  499 CPAIMSPSLFNLLQEYPDDRTARTLTLIAKVTQNLANFAKFGS---KEEYM-SFMNQFLEHEWTN-MQRFLLEISN 569
Cdd:cd05134  192 APAILSPNLFQLTPHHPDPQTSRTLTLISKTIQTLGSLSKSKSanfKESYMaAFYDYFNEQKYADaVKNFLDLISS 267
RasGAP_Neurofibromin cd05130
Ras-GTPase Activating Domain of neurofibromin; Neurofibromin is the product of the ...
 346-598 4.40e-33

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


Pssm-ID: 213332 [Multi-domain]  Cd Length: 332  Bit Score: 131.29  E-value: 4.40e-33
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94967023  346 EMASALVHILQSTGKVKDFLTDLMMSEVDRCGDNEHLiFRENTLATKAIEEYLKLVGQKYLQDALGEFIKALYESDE--N 423
Cdd:cd05130   41 ELARVLVTLFDSKHLLYQLLWNMFSKEVELADSMQTL-FRGNSLASKIMTFCFKVYGATYLQSLLEPLLRTMITSSEwvS 119

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94967023  424 CEVDPSKC-SAADLPEHQGNLKMCCELAFCKIINSYCVFPRELKEVFASWRQECSSRGrPDISERLISASLFLRFLCPAI 502
Cdd:cd05130  120 YEVDPTRLeGNENLEENQRNLLQLTEKFFHAIISSSDEFPPQLRSVCHCLYQVVSHRF-PNSGLGAVGSAIFLRFINPAI 198

                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94967023  503 MSPSLFNLLQEYPDDRTARTLTLIAKVTQNLANFAKFgSKEEYMSFMNQFLEHEWTNMQRFLLEI-SNPETLSNTAG-FE 580
Cdd:cd05130  199 VSPYEYGILDREPPPRVKRGLKLMSKILQNIANHVLF-TKEAHMLPFNDFLRNHFEAGRRFFSSIaSDCGAVDGPSSkYL 277

                        250
                 ....*....|....*...
gi 94967023  581 GYIDLGrELSSLHSLLWE 598
Cdd:cd05130  278 SFINDA-NVLALHRLLWN 294
PH_RASAL3 cd13374
RAS protein activator like-3 Pleckstrin homology (PH) domain; RASAL3 is thought to be a Ras ...
 96-198 2.93e-31

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: 119.73  E-value: 2.93e-31
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94967023   96 LMPRLKESRSHESLL------SPSSAVEA---------LDLSMEEEVVIKPVHSSILGQDYCFEVTTSSGSKCFSCRSAA 160
Cdd:cd13374   25 LLKRLKEKKKAKAEStgtgrdGPPSALGSreslatiseLDLGAERDVRVWPLHPSLLGEPHCFQVTWPGGSRCFSCRSAA 104

                         90       100       110
                 ....*....|....*....|....*....|....*...
gi 94967023  161 ERDKWMENLRRAVHPNKDNSRRVEHILKLWVIEAKDLP 198
Cdd:cd13374  105 ERDRWIEDLRRSFQPHQDNVEREETWLSVWVHEAKGLP 142
RasGAP_RASAL cd05135
Ras-GTPase Activating Domain of RASAL1 and similar proteins; Ras GTPase activating-like ...
 333-564 7.16e-30

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: 120.69  E-value: 7.16e-30
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94967023  333 AALEPILSAKTKEEMASALVHILQSTGKVKDFLTDLMMSEVDRCGDNEHLiFRENTLATKAIEEYLKLVGQKYLQDALGE 412
Cdd:cd05135   29 AMLEEVTTGESRQDVATKLVKIFLGQGLVVPFLDYLNTREVGRTTDPNTL-FRSNSLASKSMEQFMKVVGMPYLHEVLKP 107

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94967023  413 FIKALYESDENCEVDPSK--------------CSAADLPEH-----QGNLKMCCElafcKIINSYCVFPRELKEVFASWR 473
Cdd:cd05135  108 VINRIFEEKKYVELDPCKidlnrtrrisfkgsLSEAQVRESslellQGYLGSIID----AIVGSVDQCPPVMRVAFKQLH 183

                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94967023  474 QECSSR----GRPDISERLISASLFLRFLCPAIMSPSLFNLLQEYPDDRTARTLTLIAKVTQNLANF-AKFGS-KEEYMS 547
Cdd:cd05135  184 KRVEERfpeaEHQDVKYLAISGFLFLRFFAPAILTPKLFQLREQHADPRTSRTLLLLAKAVQSIGNLgLQLGQgKEQWMA 263

                        250
                 ....*....|....*..
gi 94967023  548 FMNQFLEHEWTNMQRFL 564
Cdd:cd05135  264 PLHPFILQSVARVKDFL 280
RasGAP pfam00616
GTPase-activator protein for Ras-like GTPase; All alpha-helical domain that accelerates the ...
 364-535 4.62e-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: 459871  Cd Length: 207  Bit Score: 115.85  E-value: 4.62e-29
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94967023    364 FLTDLMMSEVDRCgDNEHLIFRENTLATKAIEEYLKL-VGQKYLQDALGEFIKALYESDE-NCEVDPSK----------- 430
Cdd:pfam00616    1 LISELIEEEIESS-DNPNDLLRGNSLVSKLLETYNRRpRGQEYLKKVLGPLVRKIIEDEDlDLESDPRKiyeslinqeel 79

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94967023    431 -------------CSAADLPE-------HQGNLKMCCELAFCKIINSYCVFPREL----KEVFASWRQECssrgrPDISE 486
Cdd:pfam00616   80 ktgrsdlprdvspEEAIEDPEvrqifedNLQKLRELADEFLDAIYSSLNQLPYGIryicKQLYELLEEKF-----PDASE 154

                          170       180       190       200       210
                   ....*....|....*....|....*....|....*....|....*....|...
gi 94967023    487 R----LISASLFLRFLCPAIMSPSLFNLLQEYPDDRTARTLTLIAKVTQNLAN 535
Cdd:pfam00616  155 EeilnAIGGFLFLRFFCPAIVNPDLFGLVDHQISPKQRRNLTLIAKVLQNLAN 207
RasGAP_RASA2 cd05394
Ras-GTPase Activating Domain of RASA2; RASA2 (or GAP1(m)) is a member of the GAP1 family of ...
 351-571 4.88e-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: 117.69  E-value: 4.88e-29
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94967023  351 LVHILQSTGKVKDFLTDLMMSEVDRCGDnEHLIFRENTLATKAIEEYLKLVGQKYLQDALGEFIKALYESDENCEVDPSK 430
Cdd:cd05394   42 LVRLLLHHNKLVPFVAAVAALDLKDTQE-ANTIFRGNSLATRCLDEMMKIVGKHYLKVTLKPVLDEICESPKPCEIDPIK 120

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94967023  431 CSAADLPE-HQGNLKMCCELAFCKIINSYCVFPRELKEVFASWRQECSSR--GRPDISERLISASLFLRFLCPAIMSPSL 507
Cdd:cd05394  121 LKEGDNVEnNKENLRYYVDKVFFSIVKSSMSCPTLMCDVFRSLRHLAVKRfpNDPHVQYSAVSSFVFLRFFAVAVVSPHT 200

                        170       180       190       200       210       220       230
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|..
gi 94967023  508 FNLLQEYPDDRTARTLTLIAKVTQNLANFAKFGS------KEEYM-SFMNQFLEHEWT-NMQRFLLEISNPE 571
Cdd:cd05394  201 FQLRPHHPDAQTSRTLTLISKTIQTLGSWGSLSKsklssfKETFMcDFFKMFQEEKYIeKVKKFLDEISSTE 272
RasGAP_RASA4 cd05395
Ras-GTPase Activating Domain of RASA4; Ras GTPase activating-like 4 protein (RASAL4), also ...
 331-571 2.76e-25

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


Pssm-ID: 213343 [Multi-domain]  Cd Length: 287  Bit Score: 107.26  E-value: 2.76e-25
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94967023  331 LCAALEPILSAKTKEEMASALVHILQSTGKVKDFLTDLMMSEVDRCGDNEHLiFRENTLATKAIEEYLKLVGQKYLQDAL 410
Cdd:cd05395   27 LISLIDETTTAECRQEVATNLVKLFLGQGLAKEFLDLLFQLELDKTTEPNTL-FRSNSLASKSMESFLKVAGMQYLHSVL 105

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94967023  411 GEFIKALYESDENCEVDPSK-------CSAADLPEHQGN--------LKMCCELAFCKIINSYCVFPRELKEVFASWRQE 475
Cdd:cd05395  106 GPTINRVFEEKKYVELDPSKveikdvgCSGLHRIQTESEvieqsaqlLQSYLGELLSAISKSVKYCPAVIRATFRQLFKR 185

                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94967023  476 CSSRgRPDISER-----LISASLFLRFLCPAIMSPSLFNLLQEYPDDRTARTLTLIAKVTQNLANFAKFGS--KEEYMSF 548
Cdd:cd05395  186 VQER-FPENQHQnvkfiAVTSFLCLRFFSPAIMSPKLFHLREKHADARTSRTLLLLAKAVQNVGNMDTLASraKEAWMAP 264

                        250       260
                 ....*....|....*....|...
gi 94967023  549 MNQFLEHEWTNMQRFLLEISNPE 571
Cdd:cd05395  265 LQPAIQQGVAQLKDFITKLVDIE 287
RasGAP_GAPA cd05132
Ras-GTPase Activating Domain of GAPA; GAPA is an IQGAP-related protein and is predicted to ...
 385-615 4.54e-25

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


Pssm-ID: 213334  Cd Length: 352  Bit Score: 108.21  E-value: 4.54e-25
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94967023  385 RENTLATKAIEEYLKLV-GQKYLQDALGEFIKALYE-SDENCEVDPSKC-------------------------SAADLP 437
Cdd:cd05132   49 RANTAVSRMMTTYTRRGpGQSYLKTVLADRINDLISlKDLNLEINPLKVyeqmindieldtglpsnlprgitpeEAAENP 128

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94967023  438 EHQG----NLKMCCELA---FCKIINSYCVFPRELKEVFASWRQECSSRgRPDISER----LISASLFLRFLCPAIMSPS 506
Cdd:cd05132  129 AVQNiiepRLEMLEEITnsfLEAIINSLDEVPYGIRWICKQIRSLTRRK-FPDASDEticsLIGGFFLLRFINPAIVSPQ 207

                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94967023  507 LFNLLQEYPDDRTARTLTLIAKVTQNLANFAKFgSKEEYMSFMNQFLEHEWTNMQRFLLEISNPETLSNTAGFEGYIDLG 586
Cdd:cd05132  208 AYMLVDGKPSDNTRRTLTLIAKLLQNLANKPSY-SKEPYMAPLQPFVEENKERLNKFLNDLCEVDDFYESLELDQYIALS 286

                        250       260       270       280
                 ....*....|....*....|....*....|....*....|....*.
gi 94967023  587 R----------ELSSLHSLLWEAVSQLEQS-------IVSKLGPLP 615
Cdd:cd05132  287 KkdlsinitlnEIYNTHSLLVKHLAELAPDhndhlrlILQELGPAP 332
C2A_RasGAP cd08383
C2 domain (first repeat) of Ras GTPase activating proteins (GAPs); RasGAPs suppress Ras ...
 187-306 3.50e-11

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


Pssm-ID: 176029 [Multi-domain]  Cd Length: 117  Bit Score: 61.51  E-value: 3.50e-11
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94967023  187 LKLWVIEAKDLPAKKK---YlCELCLDDVLYARTTGKLKTdNVFWGEHFEFHNLPPL---RTVTVHLYretdKKKKKERN 260
Cdd:cd08383    2 LRLRILEAKNLPSKGTrdpY-CTVSLDQVEVARTKTVEKL-NPFWGEEFVFDDPPPDvtfFTLSFYNK----DKRSKDRD 75

                         90       100       110       120
                 ....*....|....*....|....*....|....*....|....*.
gi 94967023  261 SYLGLVSLpaASVAGRQFVEKWYPVVTPNPKGGKgPGpMIRIKARY 306
Cdd:cd08383   76 IVIGKVAL--SKLDLGQGKDEWFPLTPVDPDSEV-QG-SVRLRARY 117
C2_Ras_p21A1 cd08400
C2 domain present in RAS p21 protein activator 1 (RasA1); RasA1 is a GAP1 (GTPase activating ...
 187-306 1.10e-10

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


Pssm-ID: 176045 [Multi-domain]  Cd Length: 126  Bit Score: 60.07  E-value: 1.10e-10
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94967023  187 LKLWVIEAKDLPAKK---KYlCELCLDDVLYARTtgKLKTD-NVFWGEHFEFHNLPP-LRTVTVHLYretdKKKKKERNS 261
Cdd:cd08400    6 LQLNVLEAHKLPVKHvphPY-CVISLNEVKVART--KVREGpNPVWSEEFVFDDLPPdVNSFTISLS----NKAKRSKDS 78

                         90       100       110       120
                 ....*....|....*....|....*....|....*....|....*
gi 94967023  262 YLGLVSLPAASVAGRQFVEKWYPVVTPNPKGGKGPGpMIRIKARY 306
Cdd:cd08400   79 EIAEVTVQLSKLQNGQETDEWYPLSSASPLKGGEWG-SLRIRARY 122
C2 cd00030
C2 domain; The C2 domain was first identified in PKC. C2 domains fold into an 8-standed ...
 187-284 1.98e-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 [Multi-domain]  Cd Length: 102  Bit Score: 58.62  E-value: 1.98e-10
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94967023  187 LKLWVIEAKDLPAKKK-----YLCELCLDDVLYARTTGKLKTDNVFWGEHFEFHNLPPL-RTVTVHLYretDKKKKKeRN 260
Cdd:cd00030    1 LRVTVIEARNLPAKDLngksdPYVKVSLGGKQKFKTKVVKNTLNPVWNETFEFPVLDPEsDTLTVEVW---DKDRFS-KD 76

                         90       100
                 ....*....|....*....|....*
gi 94967023  261 SYLGLVSLPAASVAGR-QFVEKWYP 284
Cdd:cd00030   77 DFLGEVEIPLSELLDSgKEGELWLP 101
C2 pfam00168
C2 domain;
185-285 1.72e-08

C2 domain;


Pssm-ID: 425499 [Multi-domain]  Cd Length: 104  Bit Score: 53.48  E-value: 1.72e-08
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94967023    185 HILKLWVIEAKDLPAKKK------YlCELCLDDVLY-ARTTGKLKTDNVFWGEHFEFH-NLPPLRTVTVHLYretDKKKK 256
Cdd:pfam00168    1 GRLTVTVIEAKNLPPKDGngtsdpY-VKVYLLDGKQkKKTKVVKNTLNPVWNETFTFSvPDPENAVLEIEVY---DYDRF 76

                           90       100
                   ....*....|....*....|....*....
gi 94967023    257 KeRNSYLGLVSLPAASVAGRQFVEKWYPV 285
Cdd:pfam00168   77 G-RDDFIGEVRIPLSELDSGEGLDGWYPL 104
C2 smart00239
Protein kinase C conserved region 2 (CalB); Ca2+-binding motif present in phospholipases, ...
 186-282 1.85e-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 [Multi-domain]  Cd Length: 101  Bit Score: 53.26  E-value: 1.85e-08
                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94967023     186 ILKLWVIEAKDLPAKKKYL-----CELCLDDVLY--ARTTGKLKTDNVFWGEHFEFH-NLPPLRTVTVHLYretDKKKKK 257
Cdd:smart00239    1 TLTVKIISARNLPPKDKGGksdpyVKVSLDGDPKekKKTKVVKNTLNPVWNETFEFEvPPPELAELEIEVY---DKDRFG 77

                            90       100
                    ....*....|....*....|....*
gi 94967023     258 eRNSYLGLVSLPAASVAGRQFVEKW 282
Cdd:smart00239   78 -RDDFIGQVTIPLSDLLLGGRHEKL 101
RasGAP_IQGAP2 cd05131
Ras-GTPase Activating Domain of IQ motif containing GTPase activating protein 2; IQGAP2 is a ...
 391-639 9.26e-08

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


Pssm-ID: 213333 [Multi-domain]  Cd Length: 359  Bit Score: 55.39  E-value: 9.26e-08
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94967023  391 TKAIEEYLKLVGQkyLQDALGEFIKALYE-SDENCEVDPSkcSAADLPEHQGNLKMCCELAFCKIINSYCVFPRELKEVF 469
Cdd:cd05131   87 TNPVEVYKAWVNQ--LETATGEASKLPYDvTTEQALTHPE--VVNKLESSIQSLRSVTDKVLGSIFSSLDLIPYGMRYIA 162

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94967023  470 ASWRQECSSRgRPDISE----RLISASLFLRFLCPAIMSPSLFNLL------QEYPDDRtaRTLTLIAKVTQNLANFAKF 539
Cdd:cd05131  163 KVLKNSLHEK-FPDATEdellKIVGNLLYYRYMNPAIVAPDGFDIIdmtaggQIHSEQR--RNLGSVAKVLQHAASNKLF 239

                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94967023  540 GSKEEYMSFMNQFLEHEWTNMQRFL---LEISNPETLSNTAGFEGYIDLGR--------ELSSLHSLLWE---AVSQLEQ 605
Cdd:cd05131  240 EGENAHLSSMNSYLSQTYQKFRKFFqaaCDVPEPEEKFNIDEYSDMVTLSKpviyisieEIINTHSLLLEhqdAIAPDQN 319

                        250       260       270
                 ....*....|....*....|....*....|....*...
gi 94967023  606 SIVSK----LGPLPrilrDVHTALstpGSGQLpGTNDL 639
Cdd:cd05131  320 DLLHEllkdLGEVP----DVESFL---GEGTV-DPNDP 349
PH smart00233
Pleckstrin homology domain; Domain commonly found in eukaryotic signalling proteins. The ...
 121-174 2.02e-06

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


Pssm-ID: 214574 [Multi-domain]  Cd Length: 102  Bit Score: 47.54  E-value: 2.02e-06
                            10        20        30        40        50
                    ....*....|....*....|....*....|....*....|....*....|....*
gi 94967023     121 LSMEEEVVIKPVHSSILGQDYCFEVTTSSG-SKCFSCRSAAERDKWMENLRRAVH 174
Cdd:smart00233   48 IDLSGCTVREAPDPDSSKKPHCFEIKTSDRkTLLLQAESEEEREKWVEALRKAIA 102
RasGAP_IQGAP_like cd05127
Ras-GTPase Activating Domain of IQ motif containing GTPase activating proteins; This family ...
 493-617 4.89e-06

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


Pssm-ID: 213329 [Multi-domain]  Cd Length: 331  Bit Score: 49.89  E-value: 4.89e-06
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94967023  493 LFLRFLCPAIMSPSLFNLLQEYPDDRTA----RTLTLIAKVTQNLANFAKFGSKEEYMSFMNQFLEHEWTNMQRFLLEIS 568
Cdd:cd05127  179 LYYRYMNPAIVAPEAFDIIDLSVGGQLSplqrRNLGSIAKVLQQAASGKLFGGENPYLSPLNPYISESHEKFKKFFLEAC 258

                         90       100       110       120       130       140
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 94967023  569 NPETLSNTAGFEGYIDLG-----------RELSSLHSLLWEAVSQLEQS-------IVSKLGPLPRI 617
Cdd:cd05127  259 TVPEAEEHFNIDEYSDLTmltkptiyislQEIFATHKLLLEHQDEIAPDpddplreLLDDLGPAPTI 325
SMC_prok_B TIGR02168
chromosome segregation protein SMC, common bacterial type; SMC (structural maintenance of ...
 992-1132 1.31e-05

chromosome segregation protein SMC, common bacterial type; SMC (structural maintenance of chromosomes) proteins bind DNA and act in organizing and segregating chromosomes for partition. SMC proteins are found in bacteria, archaea, and eukaryotes. This family represents the SMC protein of most bacteria. The smc gene is often associated with scpB (TIGR00281) and scpA genes, where scp stands for segregation and condensation protein. SMC was shown (in Caulobacter crescentus) to be induced early in S phase but present and bound to DNA throughout the cell cycle. [Cellular processes, Cell division, DNA metabolism, Chromosome-associated proteins]


Pssm-ID: 274008 [Multi-domain]  Cd Length: 1179  Bit Score: 49.67  E-value: 1.31e-05
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94967023    992 GPDPPHRDRLRSKDELSQAEKDLAVLQDKLRISTKKLEEYETLF-----------KCQEETTQKLVLEYQ--ARLEEGEE 1058
Cdd:TIGR02168  664 GSAKTNSSILERRREIEELEEKIEELEEKIAELEKALAELRKELeeleeeleqlrKELEELSRQISALRKdlARLEAEVE 743

                           90       100       110       120       130       140       150
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 94967023   1059 RLRRQQEDKDIQMKGIISRLMSVEEELKKDHAEMQAAVDSKQKI---IDAQEKRIASLDAANARLMSALTQLKESMH 1132
Cdd:TIGR02168  744 QLEERIAQLSKELTELEAEIEELEERLEEAEEELAEAEAEIEELeaqIEQLKEELKALREALDELRAELTLLNEEAA 820
C2A_MCTP_PRT_plant cd04022
C2 domain first repeat found in Multiple C2 domain and Transmembrane region Proteins (MCTP); ...
 191-284 3.61e-05

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


Pssm-ID: 175989 [Multi-domain]  Cd Length: 127  Bit Score: 44.64  E-value: 3.61e-05
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94967023  191 VIEAKDLPAKKKY-----LCELCLDDVLYaRTTGKLKTDNVFWGEHFEF--HNLPPLRTVTVHLYRETDKKKKKeRNSYL 263
Cdd:cd04022    6 VVDAQDLMPKDGQgsssaYVELDFDGQKK-RTRTKPKDLNPVWNEKLVFnvSDPSRLSNLVLEVYVYNDRRSGR-RRSFL 83

                         90       100
                 ....*....|....*....|..
gi 94967023  264 GLVSLPAASVAGRQ-FVEKWYP 284
Cdd:cd04022   84 GRVRISGTSFVPPSeAVVQRYP 105
RasGAP_IQGAP1 cd05133
Ras-GTPase Activating Domain of IQ motif containing GTPase activating protein 1; IQGAP1 is a ...
 482-585 3.98e-05

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


Pssm-ID: 213335  Cd Length: 380  Bit Score: 47.35  E-value: 3.98e-05
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94967023  482 PDISE----RLISASLFLRFLCPAIMSPSLFNLL------QEYPDDRtaRTLTLIAKVTQNLANFAKFGSKEEYMSFMNQ 551
Cdd:cd05133  174 PDAGEdellKIVGNLLYYRYMNPAIVAPDAFDIIdlsaggQLTTDQR--RNLGSIAKMLQHAASNKMFLGDNAHLSPINE 251

                         90       100       110
                 ....*....|....*....|....*....|....
gi 94967023  552 FLEHEWTNMQRFLLEISNPETLSNTAGFEGYIDL 585
Cdd:cd05133  252 YLSQSYQKFRRFFQAACDVPELEDKFNVDEYSDL 285
PRK03918 PRK03918
DNA double-strand break repair ATPase Rad50;
1004-1129 4.46e-05

DNA double-strand break repair ATPase Rad50;


Pssm-ID: 235175 [Multi-domain]  Cd Length: 880  Bit Score: 47.75  E-value: 4.46e-05
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94967023  1004 KDELSQAEKDLAVLQDKLRISTKKLEEYETLFKCQEETTQKLVlEYQARLEEGEERLRRQQEDKDI--QMKGIISRLMSV 1081
Cdd:PRK03918  306 LDELREIEKRLSRLEEEINGIEERIKELEEKEERLEELKKKLK-ELEKRLEELEERHELYEEAKAKkeELERLKKRLTGL 384

                          90       100       110       120       130
                  ....*....|....*....|....*....|....*....|....*....|..
gi 94967023  1082 E-EELKKdhaEMQAAVDSKQKIIDAQEK---RIASLDAANARLMSALTQLKE 1129
Cdd:PRK03918  385 TpEKLEK---ELEELEKAKEEIEEEISKitaRIGELKKEIKELKKAIEELKK 433
C2A_C2C_Synaptotagmin_like cd08391
C2 domain first and third repeat in Synaptotagmin-like proteins; Synaptotagmin is a ...
 185-284 4.65e-05

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


Pssm-ID: 176037 [Multi-domain]  Cd Length: 121  Bit Score: 43.82  E-value: 4.65e-05
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94967023  185 HILKLWVIEAKDLPAKKKYL-----------CELCLDDVLYaRTTGKLKTDNVFWGEHFEF--HNLPPLrTVTVHLYret 251
Cdd:cd08391    1 GVLRIHVIEAQDLVAKDKFVgglvkgksdpyVIVRVGAQTF-KSKVIKENLNPKWNEVYEAvvDEVPGQ-ELEIELF--- 75

                         90       100       110
                 ....*....|....*....|....*....|...
gi 94967023  252 DKKKKKErnSYLGLVSLPAASVAGRQFVEKWYP 284
Cdd:cd08391   76 DEDPDKD--DFLGRLSIDLGSVEKKGFIDEWLP 106
Smc COG1196
Chromosome segregation ATPase Smc [Cell cycle control, cell division, chromosome partitioning]; ...
 1004-1129 6.14e-05

Chromosome segregation ATPase Smc [Cell cycle control, cell division, chromosome partitioning];


Pssm-ID: 440809 [Multi-domain]  Cd Length: 983  Bit Score: 47.24  E-value: 6.14e-05
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94967023 1004 KDELSQAEKDLAVLQDKLRISTKKLEEYETLFKCQEETTQKLVLEyQARLEEGEERLRRQQEDKDIQMKGIISRLMSVEE 1083
Cdd:COG1196  273 RLELEELELELEEAQAEEYELLAELARLEQDIARLEERRRELEER-LEELEEELAELEEELEELEEELEELEEELEEAEE 351

                         90       100       110       120
                 ....*....|....*....|....*....|....*....|....*.
gi 94967023 1084 ELKKDHAEMQAAVDSKQKIIDAQEKRIASLDAANARLMSALTQLKE 1129
Cdd:COG1196  352 ELEEAEAELAEAEEALLEAEAELAEAEEELEELAEELLEALRAAAE 397
RasGAP_IQGAP3 cd12207
Ras-GTPase Activating Domain of IQ motif containing GTPase activating protein 3; This family ...
 493-640 8.01e-05

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


Pssm-ID: 213346 [Multi-domain]  Cd Length: 350  Bit Score: 46.36  E-value: 8.01e-05
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94967023  493 LFLRFLCPAIMSPSLFNLLQE------YPDDRtaRTLTLIAKVTQNLANFAKFGSKEEYMSFMNQFLEHEWTNMQRFLLE 566
Cdd:cd12207  189 LYYRFMNPAVVAPDGFDIVDCsaggalQPEQR--RMLGSVAKVLQHAAANKHFQGDSEHLQALNQYLEETHVKFRKFILQ 266

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94967023  567 ---ISNPETLSNTAGFEG---------YIDLGrELSSLHSLLWEAvsqlEQSIVSK-LGPLPRILRDVhtalstpgsGQL 633
Cdd:cd12207  267 accVPEPEERFNVDEYSEmvavakpviYITVG-ELINTHKLLLEH----QDSIAPDhSDPLHELLEDL---------GEV 332


                 ....*..
gi 94967023  634 PGTNDLA 640
Cdd:cd12207  333 PTVQSLI 339
SMC_prok_B TIGR02168
chromosome segregation protein SMC, common bacterial type; SMC (structural maintenance of ...
 999-1129 1.38e-04

chromosome segregation protein SMC, common bacterial type; SMC (structural maintenance of chromosomes) proteins bind DNA and act in organizing and segregating chromosomes for partition. SMC proteins are found in bacteria, archaea, and eukaryotes. This family represents the SMC protein of most bacteria. The smc gene is often associated with scpB (TIGR00281) and scpA genes, where scp stands for segregation and condensation protein. SMC was shown (in Caulobacter crescentus) to be induced early in S phase but present and bound to DNA throughout the cell cycle. [Cellular processes, Cell division, DNA metabolism, Chromosome-associated proteins]


Pssm-ID: 274008 [Multi-domain]  Cd Length: 1179  Bit Score: 46.20  E-value: 1.38e-04
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94967023    999 DRLRS-KDELSQAEKDLAVLQDKLRISTKKLEEYETLF----------KCQEETTQKLVLEYQARLEEGEERLRRQQE-- 1065
Cdd:TIGR02168  232 LRLEElREELEELQEELKEAEEELEELTAELQELEEKLeelrlevselEEEIEELQKELYALANEISRLEQQKQILRErl 311

                           90       100       110       120       130       140
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 94967023   1066 ---DKDIQMK-GIISRLMSVEEELKKDHAEMQAAVDSKQKIIDAQEKRIASLDAANARLMSALTQLKE 1129
Cdd:TIGR02168  312 anlERQLEELeAQLEELESKLDELAEELAELEEKLEELKEELESLEAELEELEAELEELESRLEELEE 379
COG4372 COG4372
Uncharacterized protein, contains DUF3084 domain [Function unknown];
1004-1130 1.96e-04

Uncharacterized protein, contains DUF3084 domain [Function unknown];


Pssm-ID: 443500 [Multi-domain]  Cd Length: 370  Bit Score: 45.28  E-value: 1.96e-04
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94967023 1004 KDELSQAEKDLAVLQDKLRISTKKLEEYETlfkcQEETTQKLVLEYQARLEEGEERLRRQQEDKDiQMKGIISRLMSVEE 1083
Cdd:COG4372   51 REELEQAREELEQLEEELEQARSELEQLEE----ELEELNEQLQAAQAELAQAQEELESLQEEAE-ELQEELEELQKERQ 125

                         90       100       110       120
                 ....*....|....*....|....*....|....*....|....*..
gi 94967023 1084 ELKKDHAEMQAAVDSKQKIIDAQEKRIASLDAANARLMSALTQLKES 1130
Cdd:COG4372  126 DLEQQRKQLEAQIAELQSEIAEREEELKELEEQLESLQEELAALEQE 172
COG4372 COG4372
Uncharacterized protein, contains DUF3084 domain [Function unknown];
1002-1129 5.18e-04

Uncharacterized protein, contains DUF3084 domain [Function unknown];


Pssm-ID: 443500 [Multi-domain]  Cd Length: 370  Bit Score: 43.74  E-value: 5.18e-04
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94967023 1002 RSKDELSQAEKDLAVLQDKLRISTKKLEEYETLfkcQEETTQKLvleyqARLEEGEERLRRQQEdkdiQMKGIISRLMSV 1081
Cdd:COG4372   63 QLEEELEQARSELEQLEEELEELNEQLQAAQAE---LAQAQEEL-----ESLQEEAEELQEELE----ELQKERQDLEQQ 130

                         90       100       110       120
                 ....*....|....*....|....*....|....*....|....*...
gi 94967023 1082 EEELKKDHAEMQAAVDSKQKIIDAQEKRIASLDAANARLMSALTQLKE 1129
Cdd:COG4372  131 RKQLEAQIAELQSEIAEREEELKELEEQLESLQEELAALEQELQALSE 178
C2A_Rasal1_RasA4 cd04054
C2 domain first repeat present in RasA1 and RasA4; Rasal1 and RasA4 are both members of GAP1 ...
 191-282 9.18e-04

C2 domain first repeat present in RasA1 and RasA4; Rasal1 and RasA4 are both members of GAP1 (GTPase activating protein 1). Rasal1 responds to repetitive Ca2+ signals by associating with the plasma membrane and deactivating Ras. RasA4 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. Both of these proteins contains two C2 domains, a Ras-GAP domain, a plextrin homology (PH)-like domain, and a Bruton's Tyrosine Kinase (BTK) 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: 176018 [Multi-domain]  Cd Length: 121  Bit Score: 40.19  E-value: 9.18e-04
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94967023  191 VIEAKDLPAK-----KKYLCELCLDDVLYARTTGKLKTDNVFWGEHFEFHNLPPLRTVTVHLYREtdkkKKKERNSYLGL 265
Cdd:cd04054    6 IVEGKNLPAKditgsSDPYCIVKVDNEVIIRTATVWKTLNPFWGEEYTVHLPPGFHTVSFYVLDE----DTLSRDDVIGK 81

                         90
                 ....*....|....*...
gi 94967023  266 VSLPAASVAGR-QFVEKW 282
Cdd:cd04054   82 VSLTREVISAHpRGIDGW 99
DR0291 COG1579
Predicted nucleic acid-binding protein DR0291, contains C4-type Zn-ribbon domain [General ...
 998-1131 1.23e-03

Predicted nucleic acid-binding protein DR0291, contains C4-type Zn-ribbon domain [General function prediction only];


Pssm-ID: 441187 [Multi-domain]  Cd Length: 236  Bit Score: 41.83  E-value: 1.23e-03
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94967023  998 RDRL-RSKDELSQAEKDLAVLQDKLRISTKKLEEYETlfKCQEETTQKlvlEYQARLEEgEERLRRQQEDKDIQMKGIIS 1076
Cdd:COG1579   44 EARLeAAKTELEDLEKEIKRLELEIEEVEARIKKYEE--QLGNVRNNK---EYEALQKE-IESLKRRISDLEDEILELME 117

                         90       100       110       120       130
                 ....*....|....*....|....*....|....*....|....*....|....*
gi 94967023 1077 RLMSVEEELKKDHAEMQAAVDSKQKIIDAQEKRIASLDAANARLMSALTQLKESM 1131
Cdd:COG1579  118 RIEELEEELAELEAELAELEAELEEKKAELDEELAELEAELEELEAEREELAAKI 172
PH cd00821
Pleckstrin homology (PH) domain; PH domains have diverse functions, but in general are ...
 121-169 2.20e-03

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


Pssm-ID: 275388 [Multi-domain]  Cd Length: 92  Bit Score: 38.29  E-value: 2.20e-03
                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|
gi 94967023  121 LSMEEEVVIKPVHSSilGQDYCFEVTTSSGSK-CFSCRSAAERDKWMENL 169
Cdd:cd00821   45 IPLSGILEVEEVSPK--ERPHCFELVTPDGRTyYLQADSEEERQEWLKAL 92
COG4372 COG4372
Uncharacterized protein, contains DUF3084 domain [Function unknown];
1004-1129 2.22e-03

Uncharacterized protein, contains DUF3084 domain [Function unknown];


Pssm-ID: 443500 [Multi-domain]  Cd Length: 370  Bit Score: 41.81  E-value: 2.22e-03
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94967023 1004 KDELSQAEKDLAVLQDKLRISTKKLEEYETlfkcQEETTQKLVLEYQARLEEGEERLRRQQEdkdiQMKGIISRLMSVEE 1083
Cdd:COG4372   44 QEELEQLREELEQAREELEQLEEELEQARS----ELEQLEEELEELNEQLQAAQAELAQAQE----ELESLQEEAEELQE 115

                         90       100       110       120
                 ....*....|....*....|....*....|....*....|....*.
gi 94967023 1084 ELKKDHAEMQAAVDSKQKIIDAQEKRIASLDAANARLMSALTQLKE 1129
Cdd:COG4372  116 ELEELQKERQDLEQQRKQLEAQIAELQSEIAEREEELKELEEQLES 161
Smc COG1196
Chromosome segregation ATPase Smc [Cell cycle control, cell division, chromosome partitioning]; ...
 998-1129 2.33e-03

Chromosome segregation ATPase Smc [Cell cycle control, cell division, chromosome partitioning];


Pssm-ID: 440809 [Multi-domain]  Cd Length: 983  Bit Score: 42.23  E-value: 2.33e-03
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94967023  998 RDRLRSKDELSQAEKDLAVLQDKLRISTKKLEEYETlfkcQEETTQKLVLEYQARLEEGEERLRRQQEDKDIQMKGIISR 1077
Cdd:COG1196  309 ERRRELEERLEELEEELAELEEELEELEEELEELEE----ELEEAEEELEEAEAELAEAEEALLEAEAELAEAEEELEEL 384

                         90       100       110       120       130
                 ....*....|....*....|....*....|....*....|....*....|..
gi 94967023 1078 LmSVEEELKKDHAEMQAAVDSKQKIIDAQEKRIASLDAANARLMSALTQLKE 1129
Cdd:COG1196  385 A-EELLEALRAAAELAAQLEELEEAEEALLERLERLEEELEELEEALAELEE 435
C2_plant_PLD cd04015
C2 domain present in plant phospholipase D (PLD); PLD hydrolyzes terminal phosphodiester bonds ...
 263-306 2.40e-03

C2 domain present in plant phospholipase D (PLD); PLD hydrolyzes terminal phosphodiester bonds in diester glycerophospholipids resulting in the degradation of phospholipids. In vitro PLD transfers phosphatidic acid to primary alcohols. In plants PLD plays a role in germination, seedling growth, phosphatidylinositol metabolism, and changes in phospholipid composition. There is a single Ca(2+)/phospholipid-binding C2 domain in PLD. 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: 175982 [Multi-domain]  Cd Length: 158  Bit Score: 39.98  E-value: 2.40e-03
                         10        20        30        40
                 ....*....|....*....|....*....|....*....|....
gi 94967023  263 LGLVSLPAASVAGRQFVEKWYPVVTPNPKGGKgPGPMIRIKARY 306
Cdd:cd04015  115 IGRAYIPVEDLLSGEPVEGWLPILDSNGKPPK-PGAKIRVSLQF 157
C2A_RasA2_RasA3 cd08401
C2 domain first repeat present in RasA2 and RasA3; RasA2 and RasA3 are GAP1s (GTPase ...
 189-285 2.72e-03

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


Pssm-ID: 176046 [Multi-domain]  Cd Length: 121  Bit Score: 38.96  E-value: 2.72e-03
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94967023  189 LWVI-EAKDLPAKKK------YLCELCLDDVLYARTTGKLKTDNVFWGEHFEFHNLPPLRTVTVHLYretdKKKKKERNS 261
Cdd:cd08401    3 KIKIgEAKNLPPRSGpnkmrdCYCTVNLDQEEVFRTKTVEKSLCPFFGEDFYFEIPRTFRHLSFYIY----DRDVLRRDS 78

                         90       100
                 ....*....|....*....|....
gi 94967023  262 YLGLVSLPAASVAGRQFVEKWYPV 285
Cdd:cd08401   79 VIGKVAIKKEDLHKYYGKDTWFPL 102
rad50 TIGR00606
rad50; All proteins in this family for which functions are known are involvedin recombination, ...
 1000-1131 3.47e-03

rad50; All proteins in this family for which functions are known are involvedin recombination, recombinational repair, and/or non-homologous end joining.They are components of an exonuclease complex with MRE11 homologs. This family is distantly related to the SbcC family of bacterial proteins.This family is based on the phylogenomic analysis of JA Eisen (1999, Ph.D. Thesis, Stanford University).


Pssm-ID: 129694 [Multi-domain]  Cd Length: 1311  Bit Score: 41.57  E-value: 3.47e-03
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94967023   1000 RLRSKDELSQAEKDLAVLQDKLRISTKKLEEYETLFKCQEETTQKlvleYQARLEEGEERLRRQQEDKDiQMKGIISRLM 1079
Cdd:TIGR00606  400 IERQEDEAKTAAQLCADLQSKERLKQEQADEIRDEKKGLGRTIEL----KKEILEKKQEELKFVIKELQ-QLEGSSDRIL 474

                           90       100       110       120       130
                   ....*....|....*....|....*....|....*....|....*....|..
gi 94967023   1080 SVEEELKKDHAEMQAAvdSKQKIIDAQEKRIASLDAANARLMSALTQLKESM 1131
Cdd:TIGR00606  475 ELDQELRKAERELSKA--EKNSLTETLKKEVKSLQNEKADLDRKLRKLDQEM 524
YhaN COG4717
Uncharacterized conserved protein YhaN, contains AAA domain [Function unknown];
1006-1120 3.65e-03

Uncharacterized conserved protein YhaN, contains AAA domain [Function unknown];


Pssm-ID: 443752 [Multi-domain]  Cd Length: 641  Bit Score: 41.29  E-value: 3.65e-03
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94967023 1006 ELSQAEKDLAVLQDKLRISTKKLEEYETLfkcqEETTQKLvleyQARLEEGEERLRRQQEDKDIQMKGIISRLMSVEEEL 1085
Cdd:COG4717  133 ELEALEAELAELPERLEELEERLEELREL----EEELEEL----EAELAELQEELEELLEQLSLATEEELQDLAEELEEL 204

                         90       100       110
                 ....*....|....*....|....*....|....*
gi 94967023 1086 KKDHAEMQAAVDSKQKIIDAQEKRIASLDAANARL 1120
Cdd:COG4717  205 QQRLAELEEELEEAQEELEELEEELEQLENELEAA 239
Smc COG1196
Chromosome segregation ATPase Smc [Cell cycle control, cell division, chromosome partitioning]; ...
 998-1130 3.75e-03

Chromosome segregation ATPase Smc [Cell cycle control, cell division, chromosome partitioning];


Pssm-ID: 440809 [Multi-domain]  Cd Length: 983  Bit Score: 41.46  E-value: 3.75e-03
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94967023  998 RDRLRSKD------ELSQAEKDLAVLQDKLRISTKKLEEYETlfkcQEETTQKLVLEYQARLEEGEERLRRQQED----- 1066
Cdd:COG1196  219 KEELKELEaellllKLRELEAELEELEAELEELEAELEELEA----ELAELEAELEELRLELEELELELEEAQAEeyell 294

                         90       100       110       120       130       140
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 94967023 1067 -KDIQMKGIISRLMSVEEELKKDHAEMQAAVDSKQKIIDAQEKRIASLDAANARLMSALTQLKES 1130
Cdd:COG1196  295 aELARLEQDIARLEERRRELEERLEELEEELAELEEELEELEEELEELEEELEEAEEELEEAEAE 359
RasGAP_RAP6 cd05129
Ras-GTPase Activating Domain of Rab5-activating protein 6; Rab5-activating protein 6 (RAP6) is ...
 397-552 3.87e-03

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: 40.79  E-value: 3.87e-03
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94967023  397 YLKLVGQKYLQDALGEFIKALYESDE-NCEVDPSKCSAA-------------DLPEHQGNLKMCCE------LAFCKII- 455
Cdd:cd05129  104 ELLFSAKLYLTAALHKPIMQVLVDDEiFLETDPQKALCRfspaeqekrfgeeGTPEQQRKLQQYRAeflsrlVALVNKFi 183

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94967023  456 -----NSYCvFPRELKE-VFASWRQECSSRGRPDISERLISASL-FLRFLCPAIMSPSLFNLLQEYPDDRTAR-TLTLIA 527
Cdd:cd05129  184 sslrqSVYC-FPQSLRWiVRQLRKILTRSGDDEEAEARALCTDLlFTNFICPAIVNPEQYGIISDAPISEVARhNLMQVA 262

                        170       180
                 ....*....|....*....|....*.
gi 94967023  528 KVTQNLAnFAKFGSKE-EYMSFMNQF 552
Cdd:cd05129  263 QILQVLA-LTEFESPDpRLKELLSKF 287
DR0291 COG1579
Predicted nucleic acid-binding protein DR0291, contains C4-type Zn-ribbon domain [General ...
 999-1129 4.60e-03

Predicted nucleic acid-binding protein DR0291, contains C4-type Zn-ribbon domain [General function prediction only];


Pssm-ID: 441187 [Multi-domain]  Cd Length: 236  Bit Score: 39.91  E-value: 4.60e-03
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94967023  999 DRLRSkdELSQAEKDLAVLQDKLRISTKKLEEYETLFKCQEETTQKL---VLEYQARLEEGEERLRRQQEDKDIQ----- 1070
Cdd:COG1579   20 DRLEH--RLKELPAELAELEDELAALEARLEAAKTELEDLEKEIKRLeleIEEVEARIKKYEEQLGNVRNNKEYEalqke 97

                         90       100       110       120       130       140
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 94967023 1071 ---MKGIISRLMSVEEELKKDHAEMQAAVDSKQKIIDAQEKRI----ASLDAANARLMSALTQLKE 1129
Cdd:COG1579   98 iesLKRRISDLEDEILELMERIEELEEELAELEAELAELEAELeekkAELDEELAELEAELEELEA 163
Smc COG1196
Chromosome segregation ATPase Smc [Cell cycle control, cell division, chromosome partitioning]; ...
 999-1129 5.68e-03

Chromosome segregation ATPase Smc [Cell cycle control, cell division, chromosome partitioning];


Pssm-ID: 440809 [Multi-domain]  Cd Length: 983  Bit Score: 41.08  E-value: 5.68e-03
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94967023  999 DRLRSKDELSQAEKDLAVLQDKLRISTKKLEEYETlfkcQEETTQKLVLEYQARLEEGEERLRRQQEDKDiQMKGIISRL 1078
Cdd:COG1196  289 EEYELLAELARLEQDIARLEERRRELEERLEELEE----ELAELEEELEELEEELEELEEELEEAEEELE-EAEAELAEA 363

                         90       100       110       120       130
                 ....*....|....*....|....*....|....*....|....*....|.
gi 94967023 1079 MSVEEELKKDHAEMQAAVDSKQKIIDAQEKRIASLDAANARLMSALTQLKE 1129
Cdd:COG1196  364 EEALLEAEAELAEAEEELEELAEELLEALRAAAELAAQLEELEEAEEALLE 414
PH_RASA1 cd13260
RAS p21 protein activator (GTPase activating protein) 1 Pleckstrin homology (PH) domain; RASA1 ...
 119-171 6.62e-03

RAS p21 protein activator (GTPase activating protein) 1 Pleckstrin homology (PH) domain; RASA1 (also called RasGap1 or p120) is a member of the RasGAP family of GTPase-activating proteins. RASA1 contains N-terminal SH2-SH3-SH2 domains, followed by two C2 domains, a PH domain, a RasGAP domain, and a BTK domain. Splice variants lack the N-terminal domains. It is a cytosolic vertebrate protein that acts as a suppressor of RAS via its C-terminal GAP domain function, enhancing the weak intrinsic GTPase activity of RAS proteins resulting in the inactive GDP-bound form of RAS, allowing control of cellular proliferation and differentiation. Additionally, it is involved in mitogenic signal transmission towards downstream interacting partners through its N-terminal SH2-SH3-SH2 domains. RASA1 interacts with a number of proteins including: G3BP1, SOCS3, ANXA6, Huntingtin, KHDRBS1, Src, EPHB3, EPH receptor B2, Insulin-like growth factor 1 receptor, PTK2B, DOK1, PDGFRB, HCK, Caveolin 2, DNAJA3, HRAS, GNB2L1 and NCK1. PH domains have diverse functions, but in general are involved in targeting proteins to the appropriate cellular location or in the interaction with a binding partner. They share little sequence conservation, but all have a common fold, which is electrostatically polarized. Less than 10% of PH domains bind phosphoinositide phosphates (PIPs) with high affinity and specificity. PH domains are distinguished from other PIP-binding domains by their specific high-affinity binding to PIPs with two vicinal phosphate groups: PtdIns(3,4)P2, PtdIns(4,5)P2 or PtdIns(3,4,5)P3 which results in targeting some PH domain proteins to the plasma membrane. A few display strong specificity in lipid binding. Any specificity is usually determined by loop regions or insertions in the N-terminus of the domain, which are not conserved across all PH domains. PH domains are found in cellular signaling proteins such as serine/threonine kinase, tyrosine kinases, regulators of G-proteins, endocytotic GTPases, adaptors, as well as cytoskeletal associated molecules and in lipid associated enzymes.


Pssm-ID: 270080  Cd Length: 103  Bit Score: 37.32  E-value: 6.62e-03
                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|....*..
gi 94967023  119 LDLSmeeEVVIKPVHSSILGQDYCFEVTTSSGSKC----FSCRSAAERDKWMENLRR 171
Cdd:cd13260   48 IDLS---YCSLYPVHDSLFGRPNCFQIVVRALNEStityLCADTAELAQEWMRALRA 101
COG4372 COG4372
Uncharacterized protein, contains DUF3084 domain [Function unknown];
998-1122 7.29e-03

Uncharacterized protein, contains DUF3084 domain [Function unknown];


Pssm-ID: 443500 [Multi-domain]  Cd Length: 370  Bit Score: 39.89  E-value: 7.29e-03
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94967023  998 RDRLRSKDELSQAEKDLAVLQDKLRISTKKLEEYETLFKCQEETTQKLVLEYQaRLEEGEERLRRQQEDKDIQMKGIISR 1077
Cdd:COG4372   73 SELEQLEEELEELNEQLQAAQAELAQAQEELESLQEEAEELQEELEELQKERQ-DLEQQRKQLEAQIAELQSEIAEREEE 151

                         90       100       110       120
                 ....*....|....*....|....*....|....*....|....*..
gi 94967023 1078 LMSVEEELKKDHAEMQAAVDSKQKIIDAQ-EKRIASL-DAANARLMS 1122
Cdd:COG4372  152 LKELEEQLESLQEELAALEQELQALSEAEaEQALDELlKEANRNAEK 198
rad4 TIGR00605
DNA repair protein rad4; All proteins in this family for which functions are known are ...
 15-194 7.44e-03

DNA repair protein rad4; All proteins in this family for which functions are known are involved in targeting nucleotide excision repair to specific regions of the genome.This family is based on the phylogenomic analysis of JA Eisen (1999, Ph.D. Thesis, Stanford University). [DNA metabolism, DNA replication, recombination, and repair]


Pssm-ID: 273170 [Multi-domain]  Cd Length: 713  Bit Score: 40.25  E-value: 7.44e-03
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94967023     15 SPQERPGSRRSLPGSLSEKSPSmEPSAATPFRVTGFLSRRLKGSI-KRTKSQPK-LDRNHSFRH----ILPGFRSAAAaa 88
Cdd:TIGR00605  271 SILENLNVPTRLVFSDFLLSVS-KGHNDPEISSEGFVPKLSACNAnQRLIMSCEsADRTSRFRMkkdpSLPGFSAYSD-- 347

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94967023     89 aDNERSHLMPRLKESRSHESLLSPSSAVEALDLSMEEEVVIKPVHSSILGQDY-CFEVTTSSGSKCFscrsAAERDKWME 167
Cdd:TIGR00605  348 -MDKSPIFTCEEGDKFIDRWITYVDFWVEVFIEQEEKWVCVDAVHSGVVPKGVtCFEPATLMMTYVF----AYDRDGYVK 422

                          170       180
                   ....*....|....*....|....*..
gi 94967023    168 NLRRAVHPNKDNSRRVEHILKLWVIEA 194
Cdd:TIGR00605  423 DVTRRYCDQWSTKVRKRRVEKADFGET 449
SMC_prok_A TIGR02169
chromosome segregation protein SMC, primarily archaeal type; SMC (structural maintenance of ...
 998-1129 8.49e-03

chromosome segregation protein SMC, primarily archaeal type; SMC (structural maintenance of chromosomes) proteins bind DNA and act in organizing and segregating chromosomes for partition. SMC proteins are found in bacteria, archaea, and eukaryotes. It is found in a single copy and is homodimeric in prokaryotes, but six paralogs (excluded from this family) are found in eukarotes, where SMC proteins are heterodimeric. This family represents the SMC protein of archaea and a few bacteria (Aquifex, Synechocystis, etc); the SMC of other bacteria is described by TIGR02168. The N- and C-terminal domains of this protein are well conserved, but the central hinge region is skewed in composition and highly divergent. [Cellular processes, Cell division, DNA metabolism, Chromosome-associated proteins]


Pssm-ID: 274009 [Multi-domain]  Cd Length: 1164  Bit Score: 40.44  E-value: 8.49e-03
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94967023    998 RDRLRSKDELSQAEKDLAVLQDKLRISTKKLEEYETLFKCQEETTQKL----VLEYQARLEEGE---ERLRRQQEDKDIQ 1070
Cdd:TIGR02169  237 RQKEAIERQLASLEEELEKLTEEISELEKRLEEIEQLLEELNKKIKDLgeeeQLRVKEKIGELEaeiASLERSIAEKERE 316

                           90       100       110       120       130       140       150
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 94967023   1071 MKGIISRLMSVEEELKKDHAEM-----------------QAAVDSKQKIIDAQEKRIASLDAANARLMSALTQLKE 1129
Cdd:TIGR02169  317 LEDAEERLAKLEAEIDKLLAEIeelereieeerkrrdklTEEYAELKEELEDLRAELEEVDKEFAETRDELKDYRE 392
 
Blast search parameters
Data Source: Precalculated data, version = cdd.v.3.21
Preset Options:Database: CDSEARCH/cdd   Low complexity filter: no  Composition Based Adjustment: yes   E-value threshold: 0.01

References:

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