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Conserved domains on  [gi|2131077827|ref|XP_044906530|]
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inositol polyphosphate 5-phosphatase OCRL isoform X4 [Felis catus]

Protein Classification

INPP5c_INPP5B and RhoGAP_OCRL1 domain-containing protein( domain architecture ID 10173430)

INPP5c_INPP5B and RhoGAP_OCRL1 domain-containing protein

Graphical summary

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List of domain hits

Name Accession Description Interval E-value
INPP5c_INPP5B cd09093
Catalytic inositol polyphosphate 5-phosphatase (INPP5c) domain of Type II inositol ...
83-376 0e+00

Catalytic inositol polyphosphate 5-phosphatase (INPP5c) domain of Type II inositol polyphosphate 5-phosphatase I, Oculocerebrorenal syndrome of Lowe 1, and related proteins; This subfamily contains the INPP5c domain of type II inositol polyphosphate 5-phosphatase I (INPP5B), Oculocerebrorenal syndrome of Lowe 1 (OCRL-1), and related proteins. It belongs to a family of Mg2+-dependent inositol polyphosphate 5-phosphatases, which hydrolyze the 5-phosphate from the inositol ring of various 5-position phosphorylated phosphoinositides (PIs) and inositol phosphates (IPs), and to the large EEP (exonuclease/endonuclease/phosphatase) superfamily that contains functionally diverse enzymes that share a common catalytic mechanism of cleaving phosphodiester bonds. INPP5B and OCRL1 preferentially hydrolyze the 5-phosphate of phosphatidylinositol (4,5)- bisphosphate [PI(4,5)P2] and phosphatidylinositol (3,4,5)- trisphosphate [PI(3,4,5)P3]. INPP5B can also hydrolyze soluble inositol (1,4,5)-trisphosphate [I(1,4,5)P3] and inositol (1,3,4,5)-tetrakisphosphate [I(1,3,4,5)P4]. INPP5B participates in the endocytic pathway and in the early secretory pathway. In the latter, it may function in retrograde ERGIC (ER-to-Golgi intermediate compartment)-to-ER transport; it binds specific RAB proteins within the secretory pathway. In the endocytic pathway, it binds RAB5 and during endocytosis, may function in a RAB5-controlled cascade for converting PI(3,4,5)P3 to phosphatidylinositol 3-phosphate (PI3P). This cascade may link growth factor signaling and membrane dynamics. Mutation in OCRL1 is implicated in Lowe syndrome, an X-linked recessive multisystem disorder, which includes defects in eye, brain, and kidney function, and in Type 2 Dent's disease, a disorder with only the renal symptoms. OCRL-1 may have a role in membrane trafficking within the endocytic pathway and at the trans-Golgi network, and may participate in actin dynamics or signaling from endomembranes. OCRL1 and INPP5B have overlapping functions: deletion of both 5-phosphatases in mice is embryonic lethal, deletion of OCRL1 alone has no phenotype, and deletion of Inpp5b alone has only a mild phenotype (male sterility). Several of the proteins that interact with OCRL1 also bind INPP5B, for examples, inositol polyphosphate phosphatase interacting protein of 27kDa (IPIP27)A and B (also known as Ses1 and 2), and endocytic signaling adaptor APPL1. OCRL1, but not INPP5B, binds clathrin heavy chain, the plasma membrane AP2 adaptor subunit alpha-adaptin. In addition to this INPP5c domain, most proteins in this subfamily have a C-terminal RhoGAP (GTPase-activator protein [GAP] for Rho-like small GTPases) domain.


:

Pssm-ID: 197327  Cd Length: 292  Bit Score: 602.77  E-value: 0e+00
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2131077827  83 FRFFVGTWNVNGQSPDSELEPWLNCDSNPPDIYCIGFQELDLSTEAFFYFESVKEQEWSMAVERGLHSKAKYKKVQLVRL 162
Cdd:cd09093     1 FRIFVGTWNVNGQSPDESLRPWLSCDEEPPDIYAIGFQELDLSAEAFLFNDSSREQEWVKAVERGLHPDAKYKKVKLIRL 80
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2131077827 163 VGMMLLIFARKDQWQYIRDVATETVGTGIMGKMGNKGGVAVRFVFHNTTFCIVNSHLAAHVEDFERRNQDYKDICARMSF 242
Cdd:cd09093    81 VGMMLLVFVKKEHRQHIKEVAAETVGTGIMGKMGNKGGVAVRFQFHNTTFCFVNSHLAAHMEEVERRNQDYKDICARMKF 160
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2131077827 243 VVPNQtlPQLNIMKHDVVIWLGDLNYRLCMPDANEVKSLINKNDLQRLLKFDQLNIQRTQKKAFADFTEGEIKFIPTYKY 322
Cdd:cd09093   161 EDPDG--PPLSISDHDVVFWLGDLNYRIQELPTEEVKELIEKNDLEELLKYDQLNIQRRAGKVFEGFTEGEINFIPTYKY 238
                         250       260       270       280       290
                  ....*....|....*....|....*....|....*....|....*....|....
gi 2131077827 323 DSKTDRWDSSGKCRVPAWCDRILWRGTNVNQLHYRSHMELKTSDHKPVSALFHI 376
Cdd:cd09093   239 DPGTDNWDSSEKCRAPAWCDRILWRGTNIVQLSYRSHMELKTSDHKPVSALFDI 292
RhoGAP_OCRL1 cd04380
RhoGAP_OCRL1: RhoGAP (GTPase-activator protein [GAP] for Rho-like small GTPases) domain ...
511-741 8.16e-88

RhoGAP_OCRL1: RhoGAP (GTPase-activator protein [GAP] for Rho-like small GTPases) domain present in OCRL1-like proteins. OCRL1 (oculocerebrorenal syndrome of Lowe 1)-like proteins contain two conserved domains: a central inositol polyphosphate 5-phosphatase domain and a C-terminal Rho GAP domain, this GAP domain lacks the catalytic residue and therefore maybe inactive. OCRL-like proteins are type II inositol polyphosphate 5-phosphatases that can hydrolyze lipid PI(4,5)P2 and PI(3,4,5)P3 and soluble Ins(1,4,5)P3 and Ins(1,3,4,5)P4, but their individual specificities vary. The functionality of the RhoGAP domain is still unclear. Small GTPases cluster into distinct families, and all act as molecular switches, active in their GTP-bound form but inactive when GDP-bound. The Rho family of GTPases activates effectors involved in a wide variety of developmental processes, including regulation of cytoskeleton formation, cell proliferation and the JNK signaling pathway. GTPases generally have a low intrinsic GTPase hydrolytic activity but there are family-specific groups of GAPs that enhance the rate of GTP hydrolysis by several orders of magnitude.


:

Pssm-ID: 239845  Cd Length: 220  Bit Score: 275.37  E-value: 8.16e-88
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2131077827 511 FLTISGNYLPSCFGTSLEALCRMKRPIREVPVTKLIDLEEDSflekeksllqmvpldegASERPLQVPKEIWLLVDHLFK 590
Cdd:cd04380     1 FITVTGVYLPSCFGSSLETLIRLPDPGIRNLIDQLELGDNPD-----------------YSEVPLSIPKEIWRLVDYLYT 63
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2131077827 591 YACHQEDLFQTPGMQEE----LQQIIDCLDTSIPETIPGSNHSVAEALLIFLEALPEPVICYELYQRCLDSAQ-DPQNCR 665
Cdd:cd04380    64 RGLAQEGLFEEPGLPSEpgelLAEIRDALDTGSPFNSPGSAESVAEALLLFLESLPDPIIPYSLYERLLEAVAnNEEDKR 143
                         170       180       190       200       210       220       230
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 2131077827 666 QVIS-QLPRCHRNVFHYLMAFLRELLKFSKYNNVSENMIATLFTSLLLRPPPNLMARQTPSDRQRAIQFLLGFLESD 741
Cdd:cd04380   144 QVIRiSLPPVHRNVFVYLCSFLRELLSESADRGLDENTLATIFGRVLLRDPPRAGGKERRAERDRKRAFIEQFLLND 220
 
Name Accession Description Interval E-value
INPP5c_INPP5B cd09093
Catalytic inositol polyphosphate 5-phosphatase (INPP5c) domain of Type II inositol ...
83-376 0e+00

Catalytic inositol polyphosphate 5-phosphatase (INPP5c) domain of Type II inositol polyphosphate 5-phosphatase I, Oculocerebrorenal syndrome of Lowe 1, and related proteins; This subfamily contains the INPP5c domain of type II inositol polyphosphate 5-phosphatase I (INPP5B), Oculocerebrorenal syndrome of Lowe 1 (OCRL-1), and related proteins. It belongs to a family of Mg2+-dependent inositol polyphosphate 5-phosphatases, which hydrolyze the 5-phosphate from the inositol ring of various 5-position phosphorylated phosphoinositides (PIs) and inositol phosphates (IPs), and to the large EEP (exonuclease/endonuclease/phosphatase) superfamily that contains functionally diverse enzymes that share a common catalytic mechanism of cleaving phosphodiester bonds. INPP5B and OCRL1 preferentially hydrolyze the 5-phosphate of phosphatidylinositol (4,5)- bisphosphate [PI(4,5)P2] and phosphatidylinositol (3,4,5)- trisphosphate [PI(3,4,5)P3]. INPP5B can also hydrolyze soluble inositol (1,4,5)-trisphosphate [I(1,4,5)P3] and inositol (1,3,4,5)-tetrakisphosphate [I(1,3,4,5)P4]. INPP5B participates in the endocytic pathway and in the early secretory pathway. In the latter, it may function in retrograde ERGIC (ER-to-Golgi intermediate compartment)-to-ER transport; it binds specific RAB proteins within the secretory pathway. In the endocytic pathway, it binds RAB5 and during endocytosis, may function in a RAB5-controlled cascade for converting PI(3,4,5)P3 to phosphatidylinositol 3-phosphate (PI3P). This cascade may link growth factor signaling and membrane dynamics. Mutation in OCRL1 is implicated in Lowe syndrome, an X-linked recessive multisystem disorder, which includes defects in eye, brain, and kidney function, and in Type 2 Dent's disease, a disorder with only the renal symptoms. OCRL-1 may have a role in membrane trafficking within the endocytic pathway and at the trans-Golgi network, and may participate in actin dynamics or signaling from endomembranes. OCRL1 and INPP5B have overlapping functions: deletion of both 5-phosphatases in mice is embryonic lethal, deletion of OCRL1 alone has no phenotype, and deletion of Inpp5b alone has only a mild phenotype (male sterility). Several of the proteins that interact with OCRL1 also bind INPP5B, for examples, inositol polyphosphate phosphatase interacting protein of 27kDa (IPIP27)A and B (also known as Ses1 and 2), and endocytic signaling adaptor APPL1. OCRL1, but not INPP5B, binds clathrin heavy chain, the plasma membrane AP2 adaptor subunit alpha-adaptin. In addition to this INPP5c domain, most proteins in this subfamily have a C-terminal RhoGAP (GTPase-activator protein [GAP] for Rho-like small GTPases) domain.


Pssm-ID: 197327  Cd Length: 292  Bit Score: 602.77  E-value: 0e+00
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2131077827  83 FRFFVGTWNVNGQSPDSELEPWLNCDSNPPDIYCIGFQELDLSTEAFFYFESVKEQEWSMAVERGLHSKAKYKKVQLVRL 162
Cdd:cd09093     1 FRIFVGTWNVNGQSPDESLRPWLSCDEEPPDIYAIGFQELDLSAEAFLFNDSSREQEWVKAVERGLHPDAKYKKVKLIRL 80
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2131077827 163 VGMMLLIFARKDQWQYIRDVATETVGTGIMGKMGNKGGVAVRFVFHNTTFCIVNSHLAAHVEDFERRNQDYKDICARMSF 242
Cdd:cd09093    81 VGMMLLVFVKKEHRQHIKEVAAETVGTGIMGKMGNKGGVAVRFQFHNTTFCFVNSHLAAHMEEVERRNQDYKDICARMKF 160
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2131077827 243 VVPNQtlPQLNIMKHDVVIWLGDLNYRLCMPDANEVKSLINKNDLQRLLKFDQLNIQRTQKKAFADFTEGEIKFIPTYKY 322
Cdd:cd09093   161 EDPDG--PPLSISDHDVVFWLGDLNYRIQELPTEEVKELIEKNDLEELLKYDQLNIQRRAGKVFEGFTEGEINFIPTYKY 238
                         250       260       270       280       290
                  ....*....|....*....|....*....|....*....|....*....|....
gi 2131077827 323 DSKTDRWDSSGKCRVPAWCDRILWRGTNVNQLHYRSHMELKTSDHKPVSALFHI 376
Cdd:cd09093   239 DPGTDNWDSSEKCRAPAWCDRILWRGTNIVQLSYRSHMELKTSDHKPVSALFDI 292
IPPc smart00128
Inositol polyphosphate phosphatase, catalytic domain homologues; Mg(2+)-dependent/Li(+) ...
81-379 7.60e-131

Inositol polyphosphate phosphatase, catalytic domain homologues; Mg(2+)-dependent/Li(+)-sensitive enzymes.


Pssm-ID: 214525 [Multi-domain]  Cd Length: 306  Bit Score: 390.18  E-value: 7.60e-131
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2131077827   81 QNFRFFVGTWNVNGQS-PDSELEPWLNC-----DSNPPDIYCIGFQELDLSTE-AFFYFESVKEQEWSMAVERGLHSKAK 153
Cdd:smart00128   1 RDIKVLIGTWNVGGLEsPKVDVTSWLFQkievkQSEKPDIYVIGLQEVVGLAPgVILETIAGKERLWSDLLESSLNGDGQ 80
                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2131077827  154 YKKVQLVRLVGMMLLIFARKDQWQYIRDVATETVGTGIMGKMGNKGGVAVRFVFHNTTFCIVNSHLAAHVEDFERRNQDY 233
Cdd:smart00128  81 YNVLAKVYLVGILVLVFVKANHLVYIKDVETFTVKTGMGGLWGNKGAVAVRFKLSDTSFCFVNSHLAAGASNVEQRNQDY 160
                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2131077827  234 KDICARMSFVVPnqtlPQLNIMKHDVVIWLGDLNYRLCMPDANEVKSLINKNDLQRLLKFDQLNIQRTQKKAFADFTEGE 313
Cdd:smart00128 161 KTILRALSFPER----ALLSQFDHDVVFWFGDLNFRLDSPSYEEVRRKISKKEFDDLLEKDQLNRQREAGKVFKGFQEGP 236
                          250       260       270       280       290       300       310
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2131077827  314 IKFIPTYKYDS-KTDRWDSSGKCRVPAWCDRILWR--GTNVNQL-HYRSHMELKTSDHKPVSALFHIGVK 379
Cdd:smart00128 237 ITFPPTYKYDSvGTETYDTSEKKRVPAWCDRILYRsnGPELIQLsEYHSGMEITTSDHKPVFATFRLKVT 306
RhoGAP_OCRL1 cd04380
RhoGAP_OCRL1: RhoGAP (GTPase-activator protein [GAP] for Rho-like small GTPases) domain ...
511-741 8.16e-88

RhoGAP_OCRL1: RhoGAP (GTPase-activator protein [GAP] for Rho-like small GTPases) domain present in OCRL1-like proteins. OCRL1 (oculocerebrorenal syndrome of Lowe 1)-like proteins contain two conserved domains: a central inositol polyphosphate 5-phosphatase domain and a C-terminal Rho GAP domain, this GAP domain lacks the catalytic residue and therefore maybe inactive. OCRL-like proteins are type II inositol polyphosphate 5-phosphatases that can hydrolyze lipid PI(4,5)P2 and PI(3,4,5)P3 and soluble Ins(1,4,5)P3 and Ins(1,3,4,5)P4, but their individual specificities vary. The functionality of the RhoGAP domain is still unclear. Small GTPases cluster into distinct families, and all act as molecular switches, active in their GTP-bound form but inactive when GDP-bound. The Rho family of GTPases activates effectors involved in a wide variety of developmental processes, including regulation of cytoskeleton formation, cell proliferation and the JNK signaling pathway. GTPases generally have a low intrinsic GTPase hydrolytic activity but there are family-specific groups of GAPs that enhance the rate of GTP hydrolysis by several orders of magnitude.


Pssm-ID: 239845  Cd Length: 220  Bit Score: 275.37  E-value: 8.16e-88
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2131077827 511 FLTISGNYLPSCFGTSLEALCRMKRPIREVPVTKLIDLEEDSflekeksllqmvpldegASERPLQVPKEIWLLVDHLFK 590
Cdd:cd04380     1 FITVTGVYLPSCFGSSLETLIRLPDPGIRNLIDQLELGDNPD-----------------YSEVPLSIPKEIWRLVDYLYT 63
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2131077827 591 YACHQEDLFQTPGMQEE----LQQIIDCLDTSIPETIPGSNHSVAEALLIFLEALPEPVICYELYQRCLDSAQ-DPQNCR 665
Cdd:cd04380    64 RGLAQEGLFEEPGLPSEpgelLAEIRDALDTGSPFNSPGSAESVAEALLLFLESLPDPIIPYSLYERLLEAVAnNEEDKR 143
                         170       180       190       200       210       220       230
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 2131077827 666 QVIS-QLPRCHRNVFHYLMAFLRELLKFSKYNNVSENMIATLFTSLLLRPPPNLMARQTPSDRQRAIQFLLGFLESD 741
Cdd:cd04380   144 QVIRiSLPPVHRNVFVYLCSFLRELLSESADRGLDENTLATIFGRVLLRDPPRAGGKERRAERDRKRAFIEQFLLND 220
COG5411 COG5411
Phosphatidylinositol 5-phosphate phosphatase [Signal transduction mechanisms];
66-383 8.96e-67

Phosphatidylinositol 5-phosphate phosphatase [Signal transduction mechanisms];


Pssm-ID: 227698 [Multi-domain]  Cd Length: 460  Bit Score: 228.13  E-value: 8.96e-67
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2131077827  66 IKHILAKREKEYVNIQNFRFFVGTWNVNGQSPDSELEPWL---NCDSNPPDIYCIGFQELDLSTEAFF--YFESVKEQEW 140
Cdd:COG5411    13 IVAVLRQRRSKYVIEKDVSIFVSTFNPPGKPPKASTKRWLfpeIEATELADLYVVGLQEVVELTPGSIlsADPYDRLRIW 92
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2131077827 141 SMAVERGLHSKAKYKKVQLVR---LVGMMLLIFARKDQWQYIRDVATETVGTGIMGKMGNKGGVAVRFVFHNTTFCIVNS 217
Cdd:COG5411    93 ESKVLDCLNGAQSDEKYSLLRspqLGGILLRVFSLATNLPVVKPVSGTVKKTGFGGSSSNKGAVAIRFNYERTSFCFVNS 172
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2131077827 218 HLAAHVEDFERRNQDYKDIcarMSFVVPNQTLpqlNIMKHDVVIWLGDLNYRLCM-PDANEVKSLINKNDLQRLLKFDQL 296
Cdd:COG5411   173 HLAAGVNNIEERIFDYRSI---ASNICFSRGL---RIYDHDTIFWLGDLNYRVTStNEEVRPEIASDDGRLDKLFEYDQL 246
                         250       260       270       280       290       300       310       320
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2131077827 297 NIQRTQKKAFADFTEGEIKFIPTYKYDSKTDRWDSSGKCRVPAWCDRILWRGTNVNQLHYRSHMELKTSDHKPVSALFHI 376
Cdd:COG5411   247 LWEMEVGNVFPGFKEPVITFPPTYKFDYGTDEYDTSDKGRIPSWTDRILYKSEQLTPHSYSSIPHLMISDHRPVYATFRA 326

                  ....*..
gi 2131077827 377 GVKVVDE 383
Cdd:COG5411   327 KIKVVDP 333
PLN03191 PLN03191
Type I inositol-1,4,5-trisphosphate 5-phosphatase 2; Provisional
137-388 4.14e-50

Type I inositol-1,4,5-trisphosphate 5-phosphatase 2; Provisional


Pssm-ID: 215624 [Multi-domain]  Cd Length: 621  Bit Score: 185.88  E-value: 4.14e-50
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2131077827 137 EQEWSMAVERGLHSKAKYKKVQLVRLVGMMLLIFARKDQWQYIRDVATETVGTGIMGKMGNKGGVAVRFVFHNTTFCIVN 216
Cdd:PLN03191  347 YQLPEDLIKDCRKVKQKYVRIVSKQMVGIYVSVWVRKRLRRHINNLKVSPVGVGLMGYMGNKGSVSISMSLFQSRLCFVC 426
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2131077827 217 SHLAAHVEDF--ERRNQDYKDICARMSFV-VPNQTLPQlNIMKHDVVIWLGDLNYRLCMPDAnEVKSLINKNDLQRLLKF 293
Cdd:PLN03191  427 SHLTSGHKDGaeQRRNADVYEIIRRTRFSsVLDTDQPQ-TIPSHDQIFWFGDLNYRLNMLDT-EVRKLVAQKRWDELINS 504
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2131077827 294 DQLNIQRTQKKAFADFTEGEIKFIPTYKYDSKTDRW-----DSSGKCRVPAWCDRILWRGTNVNQLHYRsHMELKTSDHK 368
Cdd:PLN03191  505 DQLIKELRSGHVFDGWKEGPIKFPPTYKYEINSDRYvgenpKEGEKKRSPAWCDRILWLGKGIKQLCYK-RSEIRLSDHR 583
                         250       260
                  ....*....|....*....|
gi 2131077827 369 PVSALFHIGVKVVDERRYRK 388
Cdd:PLN03191  584 PVSSMFLVEVEVFDHRKLQR 603
RhoGAP smart00324
GTPase-activator protein for Rho-like GTPases; GTPase activator proteins towards Rho/Rac ...
576-737 1.17e-39

GTPase-activator protein for Rho-like GTPases; GTPase activator proteins towards Rho/Rac/Cdc42-like small GTPases. etter domain limits and outliers.


Pssm-ID: 214618  Cd Length: 174  Bit Score: 143.95  E-value: 1.17e-39
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2131077827  576 QVPKEIWLLVDHLFKYACHQEDLFQTPGMQEELQQIIDCLDTSIPETIPGSN---HSVAEALLIFLEALPEPVICYELYQ 652
Cdd:smart00324   2 PIPIIVEKCIEYLEKRGLDTEGIYRVSGSKSRVKELRDAFDSGPDPDLDLSEydvHDVAGLLKLFLRELPEPLITYELYE 81
                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2131077827  653 RCLDSAQDP------QNCRQVISQLPRCHRNVFHYLMAFLRELLKFSKYNNVSENMIATLFTSLLLRPPPNLMAR-QTPS 725
Cdd:smart00324  82 EFIEAAKLEdeterlRALRELLSLLPPANRATLRYLLAHLNRVAEHSEENKMTARNLAIVFGPTLLRPPDGEVASlKDIR 161
                          170
                   ....*....|..
gi 2131077827  726 DRQRAIQFLLGF 737
Cdd:smart00324 162 HQNTVIEFLIEN 173
RhoGAP pfam00620
RhoGAP domain; GTPase activator proteins towards Rho/Rac/Cdc42-like small GTPases.
578-716 2.62e-33

RhoGAP domain; GTPase activator proteins towards Rho/Rac/Cdc42-like small GTPases.


Pssm-ID: 459875  Cd Length: 148  Bit Score: 124.96  E-value: 2.62e-33
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2131077827 578 PKEIWLLVDHLFKYACHQEDLFQTPGMQEELQQIIDCLDT--SIPETIPGSN-HSVAEALLIFLEALPEPVICYELYQRC 654
Cdd:pfam00620   1 PLIVRKCVEYLEKRGLDTEGIFRVSGSASRIKELREAFDRgpDVDLDLEEEDvHVVASLLKLFLRELPEPLLTFELYEEF 80
                          90       100       110       120       130       140
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 2131077827 655 LDSAQDP------QNCRQVISQLPRCHRNVFHYLMAFLRELLKFSKYNNVSENMIATLFTSLLLRPPP 716
Cdd:pfam00620  81 IEAAKLPdeeerlEALRELLRKLPPANRDTLRYLLAHLNRVAQNSDVNKMNAHNLAIVFGPTLLRPPD 148
 
Name Accession Description Interval E-value
INPP5c_INPP5B cd09093
Catalytic inositol polyphosphate 5-phosphatase (INPP5c) domain of Type II inositol ...
83-376 0e+00

Catalytic inositol polyphosphate 5-phosphatase (INPP5c) domain of Type II inositol polyphosphate 5-phosphatase I, Oculocerebrorenal syndrome of Lowe 1, and related proteins; This subfamily contains the INPP5c domain of type II inositol polyphosphate 5-phosphatase I (INPP5B), Oculocerebrorenal syndrome of Lowe 1 (OCRL-1), and related proteins. It belongs to a family of Mg2+-dependent inositol polyphosphate 5-phosphatases, which hydrolyze the 5-phosphate from the inositol ring of various 5-position phosphorylated phosphoinositides (PIs) and inositol phosphates (IPs), and to the large EEP (exonuclease/endonuclease/phosphatase) superfamily that contains functionally diverse enzymes that share a common catalytic mechanism of cleaving phosphodiester bonds. INPP5B and OCRL1 preferentially hydrolyze the 5-phosphate of phosphatidylinositol (4,5)- bisphosphate [PI(4,5)P2] and phosphatidylinositol (3,4,5)- trisphosphate [PI(3,4,5)P3]. INPP5B can also hydrolyze soluble inositol (1,4,5)-trisphosphate [I(1,4,5)P3] and inositol (1,3,4,5)-tetrakisphosphate [I(1,3,4,5)P4]. INPP5B participates in the endocytic pathway and in the early secretory pathway. In the latter, it may function in retrograde ERGIC (ER-to-Golgi intermediate compartment)-to-ER transport; it binds specific RAB proteins within the secretory pathway. In the endocytic pathway, it binds RAB5 and during endocytosis, may function in a RAB5-controlled cascade for converting PI(3,4,5)P3 to phosphatidylinositol 3-phosphate (PI3P). This cascade may link growth factor signaling and membrane dynamics. Mutation in OCRL1 is implicated in Lowe syndrome, an X-linked recessive multisystem disorder, which includes defects in eye, brain, and kidney function, and in Type 2 Dent's disease, a disorder with only the renal symptoms. OCRL-1 may have a role in membrane trafficking within the endocytic pathway and at the trans-Golgi network, and may participate in actin dynamics or signaling from endomembranes. OCRL1 and INPP5B have overlapping functions: deletion of both 5-phosphatases in mice is embryonic lethal, deletion of OCRL1 alone has no phenotype, and deletion of Inpp5b alone has only a mild phenotype (male sterility). Several of the proteins that interact with OCRL1 also bind INPP5B, for examples, inositol polyphosphate phosphatase interacting protein of 27kDa (IPIP27)A and B (also known as Ses1 and 2), and endocytic signaling adaptor APPL1. OCRL1, but not INPP5B, binds clathrin heavy chain, the plasma membrane AP2 adaptor subunit alpha-adaptin. In addition to this INPP5c domain, most proteins in this subfamily have a C-terminal RhoGAP (GTPase-activator protein [GAP] for Rho-like small GTPases) domain.


Pssm-ID: 197327  Cd Length: 292  Bit Score: 602.77  E-value: 0e+00
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2131077827  83 FRFFVGTWNVNGQSPDSELEPWLNCDSNPPDIYCIGFQELDLSTEAFFYFESVKEQEWSMAVERGLHSKAKYKKVQLVRL 162
Cdd:cd09093     1 FRIFVGTWNVNGQSPDESLRPWLSCDEEPPDIYAIGFQELDLSAEAFLFNDSSREQEWVKAVERGLHPDAKYKKVKLIRL 80
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2131077827 163 VGMMLLIFARKDQWQYIRDVATETVGTGIMGKMGNKGGVAVRFVFHNTTFCIVNSHLAAHVEDFERRNQDYKDICARMSF 242
Cdd:cd09093    81 VGMMLLVFVKKEHRQHIKEVAAETVGTGIMGKMGNKGGVAVRFQFHNTTFCFVNSHLAAHMEEVERRNQDYKDICARMKF 160
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2131077827 243 VVPNQtlPQLNIMKHDVVIWLGDLNYRLCMPDANEVKSLINKNDLQRLLKFDQLNIQRTQKKAFADFTEGEIKFIPTYKY 322
Cdd:cd09093   161 EDPDG--PPLSISDHDVVFWLGDLNYRIQELPTEEVKELIEKNDLEELLKYDQLNIQRRAGKVFEGFTEGEINFIPTYKY 238
                         250       260       270       280       290
                  ....*....|....*....|....*....|....*....|....*....|....
gi 2131077827 323 DSKTDRWDSSGKCRVPAWCDRILWRGTNVNQLHYRSHMELKTSDHKPVSALFHI 376
Cdd:cd09093   239 DPGTDNWDSSEKCRAPAWCDRILWRGTNIVQLSYRSHMELKTSDHKPVSALFDI 292
IPPc smart00128
Inositol polyphosphate phosphatase, catalytic domain homologues; Mg(2+)-dependent/Li(+) ...
81-379 7.60e-131

Inositol polyphosphate phosphatase, catalytic domain homologues; Mg(2+)-dependent/Li(+)-sensitive enzymes.


Pssm-ID: 214525 [Multi-domain]  Cd Length: 306  Bit Score: 390.18  E-value: 7.60e-131
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2131077827   81 QNFRFFVGTWNVNGQS-PDSELEPWLNC-----DSNPPDIYCIGFQELDLSTE-AFFYFESVKEQEWSMAVERGLHSKAK 153
Cdd:smart00128   1 RDIKVLIGTWNVGGLEsPKVDVTSWLFQkievkQSEKPDIYVIGLQEVVGLAPgVILETIAGKERLWSDLLESSLNGDGQ 80
                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2131077827  154 YKKVQLVRLVGMMLLIFARKDQWQYIRDVATETVGTGIMGKMGNKGGVAVRFVFHNTTFCIVNSHLAAHVEDFERRNQDY 233
Cdd:smart00128  81 YNVLAKVYLVGILVLVFVKANHLVYIKDVETFTVKTGMGGLWGNKGAVAVRFKLSDTSFCFVNSHLAAGASNVEQRNQDY 160
                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2131077827  234 KDICARMSFVVPnqtlPQLNIMKHDVVIWLGDLNYRLCMPDANEVKSLINKNDLQRLLKFDQLNIQRTQKKAFADFTEGE 313
Cdd:smart00128 161 KTILRALSFPER----ALLSQFDHDVVFWFGDLNFRLDSPSYEEVRRKISKKEFDDLLEKDQLNRQREAGKVFKGFQEGP 236
                          250       260       270       280       290       300       310
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2131077827  314 IKFIPTYKYDS-KTDRWDSSGKCRVPAWCDRILWR--GTNVNQL-HYRSHMELKTSDHKPVSALFHIGVK 379
Cdd:smart00128 237 ITFPPTYKYDSvGTETYDTSEKKRVPAWCDRILYRsnGPELIQLsEYHSGMEITTSDHKPVFATFRLKVT 306
INPP5c cd09074
Catalytic domain of inositol polyphosphate 5-phosphatases; Inositol polyphosphate ...
83-376 1.12e-119

Catalytic domain of inositol polyphosphate 5-phosphatases; Inositol polyphosphate 5-phosphatases (5-phosphatases) are signal-modifying enzymes, which hydrolyze the 5-phosphate from the inositol ring of specific 5-position phosphorylated phosphoinositides (PIs) and inositol phosphates (IPs), such as PI(4,5)P2, PI(3,4,5)P3, PI(3,5)P2, I(1,4,5)P3, and I(1,3,4,5)P4. These enzymes are Mg2+-dependent, and belong to the large EEP (exonuclease/endonuclease/phosphatase) superfamily that contains functionally diverse enzymes that share a common catalytic mechanism of cleaving phosphodiester bonds. In addition to this INPP5c domain, 5-phosphatases often contain additional domains and motifs, such as the SH2 domain, the Sac-1 domain, the proline-rich domain (PRD), CAAX, RhoGAP (RhoGTPase-activating protein), and SKICH [SKIP (skeletal muscle- and kidney-enriched inositol phosphatase) carboxyl homology] domains, that are important for protein-protein interactions and/or for the subcellular localization of these enzymes. 5-phosphatases incorporate into large signaling complexes, and regulate diverse cellular processes including postsynaptic vesicular trafficking, insulin signaling, cell growth and survival, and endocytosis. Loss or gain of function of 5-phosphatases is implicated in certain human diseases. This family also contains a functionally unrelated nitric oxide transport protein, Cimex lectularius (bedbug) nitrophorin, which catalyzes a heme-assisted S-nitrosation of a proximal thiolate; the heme however binds at a site distinct from the active site of the 5-phosphatases.


Pssm-ID: 197308 [Multi-domain]  Cd Length: 299  Bit Score: 361.26  E-value: 1.12e-119
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2131077827  83 FRFFVGTWNVNGQ-SPDSELEPWLNCD-SNPPDIYCIGFQELDLSTEAFFYFE-SVKEQEWSMAVERGLHSKAKYKKVQL 159
Cdd:cd09074     1 VKIFVVTWNVGGGiSPPENLENWLSPKgTEAPDIYAVGVQEVDMSVQGFVGNDdSAKAREWVDNIQEALNEKENYVLLGS 80
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2131077827 160 VRLVGMMLLIFARKDQWQYIRD--VATETVGTGIMGKMGNKGGVAVRFVFHNTTFCIVNSHLAAHVEDFERRNQDYKDIC 237
Cdd:cd09074    81 AQLVGIFLFVFVKKEHLPQIKDleVEGVTVGTGGGGKLGNKGGVAIRFQINDTSFCFVNSHLAAGQEEVERRNQDYRDIL 160
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2131077827 238 ARMSFVVPNQtlPQLNIMKHDVVIWLGDLNYRLCMpDANEVKSLINKNDLQRLLKFDQLNIQRTQKKAFADFTEGEIKFI 317
Cdd:cd09074   161 SKLKFYRGDP--AIDSIFDHDVVFWFGDLNYRIDS-TDDEVRKLISQGDLDDLLEKDQLKKQKEKGKVFDGFQELPITFP 237
                         250       260       270       280       290       300
                  ....*....|....*....|....*....|....*....|....*....|....*....|..
gi 2131077827 318 PTYKYDSKTDRWDSSGKCRVPAWCDRILWR---GTNVNQLHYRSHMELKTSDHKPVSALFHI 376
Cdd:cd09074   238 PTYKFDPGTDEYDTSDKKRIPAWCDRILYKskaGSEIQPLSYTSVPLYKTSDHKPVRATFRV 299
INPP5c_ScInp51p-like cd09090
Catalytic inositol polyphosphate 5-phosphatase (INPP5c) domain of Saccharomyces cerevisiae ...
84-374 1.11e-92

Catalytic inositol polyphosphate 5-phosphatase (INPP5c) domain of Saccharomyces cerevisiae Inp51p, Inp52p, and Inp53p, and related proteins; This subfamily contains the INPP5c domain of three Saccharomyces cerevisiae synaptojanin-like inositol polyphosphate 5-phosphatases (INP51, INP52, and INP53), Schizosaccharomyces pombe synaptojanin (SPsynaptojanin), and related proteins. It belongs to a family of Mg2+-dependent inositol polyphosphate 5-phosphatases, which hydrolyze the 5-phosphate from the inositol ring of various 5-position phosphorylated phosphoinositides (PIs) and inositol phosphates (IPs), and to the large EEP (exonuclease/endonuclease/phosphatase) superfamily that contains functionally diverse enzymes that share a common catalytic mechanism of cleaving phosphodiester bonds. In addition to this INPP5c domain, these proteins have an N-terminal catalytic Sac1-like domain (found in other proteins including the phophoinositide phosphatase Sac1p), and a C-terminal proline-rich domain (PRD). The Sac1 domain allows Inp52p and Inp53p to recognize and dephosphorylate a wider range of substrates including PI3P, PI4P, and PI(3,5)P2. The Sac1 domain of Inp51p is non-functional. Disruption of any two of INP51, INP52, and INP53, in S. cerevisiae leads to abnormal vacuolar and plasma membrane morphology. During hyperosmotic stress, Inp52p and Inp53p localize at actin patches, where they may facilitate the hydrolysis of PI(4,5)P2, and consequently promote actin rearrangement to regulate cell growth. SPsynaptojanin is also active against a range of soluble and lipid inositol phosphates, including I(1,4,5)P3, I(1,3,4,5)P4, I(1,4,5,6)P4, PI(4,5)P2, and PIP3. Transformation of S. cerevisiae with a plasmid expressing the SPsynaptojanin 5-phosphatase domain rescues inp51/inp52/inp53 triple-mutant strains.


Pssm-ID: 197324  Cd Length: 291  Bit Score: 290.78  E-value: 1.11e-92
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2131077827  84 RFFVGTWNVNGQSPDSELEPWLNCDSN--PPDIYCIGFQEL-DLSTEAFFYFESVKEQEWSMAVERGLHSKAKYKKVQL- 159
Cdd:cd09090     2 NIFVGTFNVNGKSYKDDLSSWLFPEENdeLPDIVVIGLQEVvELTAGQILNSDPSKSSFWEKKIKTTLNGRGGEKYVLLr 81
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2131077827 160 -VRLVGMMLLIFARKDQWQYIRDVATETVGTGIMGKMGNKGGVAVRFVFHNTTFCIVNSHLAAHVEDFERRNQDYKDICA 238
Cdd:cd09090    82 sEQLVGTALLFFVKESQLPKVKNVEGSTKKTGLGGMSGNKGAVAIRFDYGDTSFCFVTSHLAAGLTNYEERNNDYKTIAR 161
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2131077827 239 RMSFVvPNQTLPQlnimkHDVVIWLGDLNYRLCMPDaNEVKSLINKNDLQRLLKFDQLNIQRTQKKAFADFTEGEIKFIP 318
Cdd:cd09090   162 GLRFS-RGRTIKD-----HDHVIWLGDFNYRISLTN-EDVRRFILNGKLDKLLEYDQLNQQMNAGEVFPGFSEGPITFPP 234
                         250       260       270       280       290
                  ....*....|....*....|....*....|....*....|....*....|....*.
gi 2131077827 319 TYKYDSKTDRWDSSGKCRVPAWCDRILWRGTNVNQLHYRShMELKTSDHKPVSALF 374
Cdd:cd09090   235 TYKYDKGTDNYDTSEKQRIPAWTDRILYRGENLRQLSYNS-APLRFSDHRPVYATF 289
INPP5c_Synj cd09089
Catalytic inositol polyphosphate 5-phosphatase (INPP5c) domain of synaptojanins; This ...
84-376 3.02e-90

Catalytic inositol polyphosphate 5-phosphatase (INPP5c) domain of synaptojanins; This subfamily contains the INPP5c domains of two human synaptojanins, synaptojanin 1 (Synj1) and synaptojanin 2 (Synj2), and related proteins. It belongs to a family of Mg2+-dependent inositol polyphosphate 5-phosphatases, which hydrolyze the 5-phosphate from the inositol ring of various 5-position phosphorylated phosphoinositides (PIs) and inositol phosphates (IPs). They belong to the large EEP (exonuclease/endonuclease/phosphatase) superfamily that contains functionally diverse enzymes that share a common catalytic mechanism of cleaving phosphodiester bonds. Synj1 occurs as two main isoforms: a brain enriched 145 KDa protein (Synj1-145) and a ubiquitously expressed 170KDa protein (Synj1-170). Synj1-145 participates in clathrin-mediated endocytosis. The primary substrate of the Synj1-145 INPP5c domain is PI(4,5)P2, which it converts to PI4P. Synj1-145 may work with membrane curvature sensors/generators (such as endophilin) to remove PI(4,5)P2 from curved membranes. The recruitment of the INPP5c domain of Synj1-145 to endophilin-induced membranes leads to a fragmentation and condensation of these structures. The PI(4,5)P2 to PI4P conversion may cooperate with dynamin to produce membrane fission. In addition to this INPP5c domain, Synjs contain an N-terminal Sac1-like domain; the Sac1 domain can dephosphorylate a variety of phosphoinositides in vitro. Synj2 can hydrolyze phosphatidylinositol diphosphate (PIP2) to phosphatidylinositol phosphate (PIP). Synj2 occurs as multiple alternative splice variants in various tissues. These variants share the INPP5c domain and the Sac1 domain. Synj2A is recruited to the mitochondria via its interaction with OMP25 (a mitochondrial outer membrane protein). Synj2B is found at nerve terminals in the brain and at the spermatid manchette in testis. Synj2B undergoes further alternative splicing to give 2B1 and 2B2. In clathrin-mediated endocytosis, Synj2 participates in the formation of clathrin-coated pits, and perhaps also in vesicle decoating. Rac1 GTPase regulates the intracellular localization of Synj2 forms, but not Synj1. Synj2 may contribute to the role of Rac1 in cell migration and invasion, and is a potential target for therapeutic intervention in malignant tumors.


Pssm-ID: 197323 [Multi-domain]  Cd Length: 328  Bit Score: 285.82  E-value: 3.02e-90
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2131077827  84 RFFVGTWNVNGQS-------PDSELEPWL--NC------------DSNPPDIYCIGFQEL-DLSTEAFFYFESVKEQEWS 141
Cdd:cd09089     2 RVFVGTWNVNGGKhfrsiafKHQSMTDWLldNPklagqcsndseeDEKPVDIFAIGFEEMvDLNASNIVSASTTNQKEWG 81
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2131077827 142 MAVERGLHSKAKYKKVQLVRLVGMMLLIFARKDQWQYIRDVATETVGTGIMGKMGNKGGVAVRFVFHNTTFCIVNSHLAA 221
Cdd:cd09089    82 EELQKTISRDHKYVLLTSEQLVGVCLFVFVRPQHAPFIRDVAVDTVKTGLGGAAGNKGAVAIRFLLHSTSLCFVCSHFAA 161
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2131077827 222 HVEDFERRNQDYKDICARMSFvvPNQTlpqlNIMKHDVVIWLGDLNYRLCMPDaNEVKSLINKNDLQRLLKFDQLNIQRT 301
Cdd:cd09089   162 GQSQVKERNEDFAEIARKLSF--PMGR----TLDSHDYVFWCGDFNYRIDLPN-DEVKELVRNGDWLKLLEFDQLTKQKA 234
                         250       260       270       280       290       300       310       320
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2131077827 302 QKKAFADFTEGEIKFIPTYKYDSKTDRWDSSGKCRVPAWCDRILWR------------GTNVNQ--------LHYRsHME 361
Cdd:cd09089   235 AGNVFKGFLEGEINFAPTYKYDLFSDDYDTSEKCRTPAWTDRVLWRrrkwpsdkteesLVETNDptwnpgtlLYYG-RAE 313
                         330
                  ....*....|....*
gi 2131077827 362 LKTSDHKPVSALFHI 376
Cdd:cd09089   314 LKTSDHRPVVAIIDI 328
RhoGAP_OCRL1 cd04380
RhoGAP_OCRL1: RhoGAP (GTPase-activator protein [GAP] for Rho-like small GTPases) domain ...
511-741 8.16e-88

RhoGAP_OCRL1: RhoGAP (GTPase-activator protein [GAP] for Rho-like small GTPases) domain present in OCRL1-like proteins. OCRL1 (oculocerebrorenal syndrome of Lowe 1)-like proteins contain two conserved domains: a central inositol polyphosphate 5-phosphatase domain and a C-terminal Rho GAP domain, this GAP domain lacks the catalytic residue and therefore maybe inactive. OCRL-like proteins are type II inositol polyphosphate 5-phosphatases that can hydrolyze lipid PI(4,5)P2 and PI(3,4,5)P3 and soluble Ins(1,4,5)P3 and Ins(1,3,4,5)P4, but their individual specificities vary. The functionality of the RhoGAP domain is still unclear. Small GTPases cluster into distinct families, and all act as molecular switches, active in their GTP-bound form but inactive when GDP-bound. The Rho family of GTPases activates effectors involved in a wide variety of developmental processes, including regulation of cytoskeleton formation, cell proliferation and the JNK signaling pathway. GTPases generally have a low intrinsic GTPase hydrolytic activity but there are family-specific groups of GAPs that enhance the rate of GTP hydrolysis by several orders of magnitude.


Pssm-ID: 239845  Cd Length: 220  Bit Score: 275.37  E-value: 8.16e-88
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2131077827 511 FLTISGNYLPSCFGTSLEALCRMKRPIREVPVTKLIDLEEDSflekeksllqmvpldegASERPLQVPKEIWLLVDHLFK 590
Cdd:cd04380     1 FITVTGVYLPSCFGSSLETLIRLPDPGIRNLIDQLELGDNPD-----------------YSEVPLSIPKEIWRLVDYLYT 63
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2131077827 591 YACHQEDLFQTPGMQEE----LQQIIDCLDTSIPETIPGSNHSVAEALLIFLEALPEPVICYELYQRCLDSAQ-DPQNCR 665
Cdd:cd04380    64 RGLAQEGLFEEPGLPSEpgelLAEIRDALDTGSPFNSPGSAESVAEALLLFLESLPDPIIPYSLYERLLEAVAnNEEDKR 143
                         170       180       190       200       210       220       230
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 2131077827 666 QVIS-QLPRCHRNVFHYLMAFLRELLKFSKYNNVSENMIATLFTSLLLRPPPNLMARQTPSDRQRAIQFLLGFLESD 741
Cdd:cd04380   144 QVIRiSLPPVHRNVFVYLCSFLRELLSESADRGLDENTLATIFGRVLLRDPPRAGGKERRAERDRKRAFIEQFLLND 220
INPP5c_INPP5J-like cd09094
Catalytic inositol polyphosphate 5-phosphatase (INPP5c) domain of inositol polyphosphate ...
83-376 1.72e-86

Catalytic inositol polyphosphate 5-phosphatase (INPP5c) domain of inositol polyphosphate 5-phosphatase J and related proteins; INPP5c domain of Inositol polyphosphate-5-phosphatase J (INPP5J), also known as PIB5PA or PIPP, and related proteins. This subfamily belongs to a family of Mg2+-dependent inositol polyphosphate 5-phosphatases, which hydrolyze the 5-phosphate from the inositol ring of various 5-position phosphorylated phosphoinositides (PIs) and inositol phosphates (IPs), and to the large EEP (exonuclease/endonuclease/phosphatase) superfamily that contains functionally diverse enzymes that share a common catalytic mechanism of cleaving phosphodiester bonds. INPP5J hydrolyzes PI(4,5)P2, I(1,4,5)P3, and I(1,3,4,5)P4 at ruffling membranes. These proteins contain a C-terminal, SKIP carboxyl homology domain (SKICH), which may direct plasma membrane ruffle localization.


Pssm-ID: 197328  Cd Length: 300  Bit Score: 275.02  E-value: 1.72e-86
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2131077827  83 FRFFVGTWNVNGQSPDSELEPWLNCDSNP--PDIYCIGFQELDlSTEAFFYFESVKEQEWSMAVERGLhSKAKYKKVQLV 160
Cdd:cd09094     1 LRVYVVTWNVATAPPPIDVRSLLGLQSPEvaPDIYIIGLQEVN-SKPVQFVSDLIFDDPWSDLFMDIL-SPKGYVKVSSI 78
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2131077827 161 RLVGMMLLIFARKDQWQYIRDVATETVGTGIMGKMGNKGGVAVRFVFHNTTFCIVNSHLAAHVEDFERRNQDYKDICARM 240
Cdd:cd09094    79 RLQGLLLLVFVKIQHLPFIRDVQTNYTRTGLGGYWGNKGAVTVRFSLYGHMICFLNCHLPAHMEKWEQRIDDFETILSTQ 158
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2131077827 241 SFVVPNQTlpqlNIMKHDVVIWLGDLNYRLCMPDANEVKSLINKNDLQRLLKFDQLNIQRTQKKAFADFTEGEIKFIPTY 320
Cdd:cd09094   159 VFNECNTP----SILDHDYVFWFGDLNFRIEDVSIEFVRELVNSKKYHLLLEKDQLNMAKRKEEAFQGFQEGPLNFAPTY 234
                         250       260       270       280       290       300
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 2131077827 321 KYDSKTDRWDSSGKCRVPAWCDRILWR----------GTNVNQLHYRSHMELKTSDHKPVSALFHI 376
Cdd:cd09094   235 KFDLGTDEYDTSGKKRKPAWTDRILWKvnpdasteekFLSITQTSYKSHMEYGISDHKPVTAQFRL 300
INPP5c_Synj2 cd09099
Catalytic inositol polyphosphate 5-phosphatase (INPP5c) domain of synaptojanin 2; This ...
84-376 8.33e-76

Catalytic inositol polyphosphate 5-phosphatase (INPP5c) domain of synaptojanin 2; This subfamily contains the INPP5c domains of human synaptojanin 2 (Synj2) and related proteins. It belongs to a family of Mg2+-dependent inositol polyphosphate 5-phosphatases, which hydrolyze the 5-phosphate from the inositol ring of various 5-position phosphorylated phosphoinositides (PIs) and inositol phosphates (IPs), and to the large EEP (exonuclease/endonuclease/phosphatase) superfamily that contains functionally diverse enzymes that share a common catalytic mechanism of cleaving phosphodiester bonds. Synj2 can hydrolyze phosphatidylinositol diphosphate (PIP2) to phosphatidylinositol phosphate (PIP). In addition to this INPP5c domain, these proteins contain an N-terminal Sac1-like domain; the Sac1 domain can dephosphorylate a variety of phosphoinositides in vitro. Synj2 occurs as multiple alternative splice variants in various tissues. These variants share the INPP5c domain and the Sac1 domain. Synj2A is recruited to the mitochondria via its interaction with OMP25, a mitochondrial outer membrane protein. Synj2B is found at nerve terminals in the brain and at the spermatid manchette in testis. Synj2B undergoes further alternative splicing to give 2B1 and 2B2. In clathrin-mediated endocytosis, Synj2 participates in the formation of clathrin-coated pits, and perhaps also in vesicle decoating. Rac1 GTPase regulates the intracellular localization of Synj2 forms, but not Synj1. Synj2 may contribute to the role of Rac1 in cell migration and invasion, and is a potential target for therapeutic intervention in malignant tumors.


Pssm-ID: 197333  Cd Length: 336  Bit Score: 248.01  E-value: 8.33e-76
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2131077827  84 RFFVGTWNVNGQSP-------DSELEPWL-------------NCDSNPPDIYCIGFQEL-DLSTEAFFYFESVKEQEWSM 142
Cdd:cd09099     2 RVAMGTWNVNGGKQfrsnilgTSELTDWLldspklsgtpdfqDDESNPPDIFAVGFEEMvELSAGNIVNASTTNRKMWGE 81
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2131077827 143 AVERGLHSKAKYKKVQLVRLVGMMLLIFARKDQWQYIRDVATETVGTGIMGKMGNKGGVAVRFVFHNTTFCIVNSHLAAH 222
Cdd:cd09099    82 QLQKAISRSHRYILLTSAQLVGVCLFIFVRPYHVPFIRDVAIDTVKTGMGGKAGNKGAVAIRFQFYSTSFCFICSHLTAG 161
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2131077827 223 VEDFERRNQDYKDICARMSFVVPNqtlpqlNIMKHDVVIWLGDLNYRLCMPdANEVKSLINKNDLQRLLKFDQLNIQRTQ 302
Cdd:cd09099   162 QNQVKERNEDYKEITQKLSFPMGR------NVFSHDYVFWCGDFNYRIDLT-YEEVFYFIKRQDWKKLLEFDQLQLQKSS 234
                         250       260       270       280       290       300       310       320
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2131077827 303 KKAFADFTEGEIKFIPTYKYDSKTDRWDSSGKCRVPAWCDRILW----------------------RGTNVNQ------L 354
Cdd:cd09099   235 GKIFKDFHEGTINFGPTYKYDVGSEAYDTSDKCRTPAWTDRVLWwrkkwpfektageinlldsdldFDTKIRHtwtpgaL 314
                         330       340
                  ....*....|....*....|..
gi 2131077827 355 HYRSHMELKTSDHKPVSALFHI 376
Cdd:cd09099   315 MYYGRAELQASDHRPVLAIVEV 336
INPP5c_Synj1 cd09098
Catalytic inositol polyphosphate 5-phosphatase (INPP5c) domain of synaptojanin 1; This ...
84-376 1.66e-68

Catalytic inositol polyphosphate 5-phosphatase (INPP5c) domain of synaptojanin 1; This subfamily contains the INPP5c domains of human synaptojanin 1 (Synj1) and related proteins. It belongs to a family of Mg2+-dependent inositol polyphosphate 5-phosphatases, which hydrolyze the 5-phosphate from the inositol ring of various 5-position phosphorylated phosphoinositides (PIs) and inositol phosphates (IPs), and to the large EEP (exonuclease/endonuclease/phosphatase) superfamily that contains functionally diverse enzymes that share a common catalytic mechanism of cleaving phosphodiester bonds. Synj1 occurs as two main isoforms: a brain enriched 145 KDa protein (Synj1-145) and a ubiquitously expressed 170KDa protein (Synj1-170). Synj1-145 participates in clathrin-mediated endocytosis. The primary substrate of the Synj1-145 INPP5c domain is PI(4,5)P2, which it converts to PI4P. Synj1-145 may work with membrane curvature sensors/generators (such as endophilin) to remove PI(4,5)P2 from curved membranes. The recruitment of the INPP5c domain of Synj1-145 to endophilin-induced membranes leads to a fragmentation and condensation of these structures. The PI(4,5)P2 to PI4P conversion may cooperate with dynamin to produce membrane fission. In addition to this INPP5c domain, these proteins contain an N-terminal Sac1-like domain; the Sac1 domain can dephosphorylate a variety of phosphoinositides in vitro.


Pssm-ID: 197332  Cd Length: 336  Bit Score: 228.77  E-value: 1.66e-68
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2131077827  84 RFFVGTWNVNGQSP-------DSELEPWL-------------NCDSNPPDIYCIGFQEL-DLSTEAFFYFESVKEQEWSM 142
Cdd:cd09098     2 RVCVGTWNVNGGKQfrsiafkNQTLTDWLldapkkagipefqDVRSKPVDIFAIGFEEMvELNAGNIVSASTTNQKLWAA 81
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2131077827 143 AVERGLHSKAKYKKVQLVRLVGMMLLIFARKDQWQYIRDVATETVGTGIMGKMGNKGGVAVRFVFHNTTFCIVNSHLAAH 222
Cdd:cd09098    82 ELQKTISRDQKYVLLASEQLVGVCLFVFIRPQHAPFIRDVAVDTVKTGMGGATGNKGAVAIRMLFHTTSLCFVCSHFAAG 161
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2131077827 223 VEDFERRNQDYKDICARMSFvvPNQTLpqlnIMKHDVVIWLGDLNYRLCMPDaNEVKSLINKNDLQRLLKFDQLNIQRTQ 302
Cdd:cd09098   162 QSQVKERNEDFIEIARKLSF--PMGRM----LFSHDYVFWCGDFNYRIDIPN-EEVKELIRQQNWDSLIAGDQLINQKNA 234
                         250       260       270       280       290       300       310       320
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2131077827 303 KKAFADFTEGEIKFIPTYKYDSKTDRWDSSGKCRVPAWCDRILWR------------------GTNVNQ----------- 353
Cdd:cd09098   235 GQVFRGFLEGKLDFAPTYKYDLFSDDYDTSEKCRTPAWTDRVLWRrrkwpfdrsaedldllnaSFPDNSkeqytwspgtl 314
                         330       340
                  ....*....|....*....|...
gi 2131077827 354 LHYrSHMELKTSDHKPVSALFHI 376
Cdd:cd09098   315 LHY-GRAELKTSDHRPVVALIDI 336
COG5411 COG5411
Phosphatidylinositol 5-phosphate phosphatase [Signal transduction mechanisms];
66-383 8.96e-67

Phosphatidylinositol 5-phosphate phosphatase [Signal transduction mechanisms];


Pssm-ID: 227698 [Multi-domain]  Cd Length: 460  Bit Score: 228.13  E-value: 8.96e-67
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2131077827  66 IKHILAKREKEYVNIQNFRFFVGTWNVNGQSPDSELEPWL---NCDSNPPDIYCIGFQELDLSTEAFF--YFESVKEQEW 140
Cdd:COG5411    13 IVAVLRQRRSKYVIEKDVSIFVSTFNPPGKPPKASTKRWLfpeIEATELADLYVVGLQEVVELTPGSIlsADPYDRLRIW 92
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2131077827 141 SMAVERGLHSKAKYKKVQLVR---LVGMMLLIFARKDQWQYIRDVATETVGTGIMGKMGNKGGVAVRFVFHNTTFCIVNS 217
Cdd:COG5411    93 ESKVLDCLNGAQSDEKYSLLRspqLGGILLRVFSLATNLPVVKPVSGTVKKTGFGGSSSNKGAVAIRFNYERTSFCFVNS 172
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2131077827 218 HLAAHVEDFERRNQDYKDIcarMSFVVPNQTLpqlNIMKHDVVIWLGDLNYRLCM-PDANEVKSLINKNDLQRLLKFDQL 296
Cdd:COG5411   173 HLAAGVNNIEERIFDYRSI---ASNICFSRGL---RIYDHDTIFWLGDLNYRVTStNEEVRPEIASDDGRLDKLFEYDQL 246
                         250       260       270       280       290       300       310       320
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2131077827 297 NIQRTQKKAFADFTEGEIKFIPTYKYDSKTDRWDSSGKCRVPAWCDRILWRGTNVNQLHYRSHMELKTSDHKPVSALFHI 376
Cdd:COG5411   247 LWEMEVGNVFPGFKEPVITFPPTYKFDYGTDEYDTSDKGRIPSWTDRILYKSEQLTPHSYSSIPHLMISDHRPVYATFRA 326

                  ....*..
gi 2131077827 377 GVKVVDE 383
Cdd:COG5411   327 KIKVVDP 333
INPP5c_SHIP cd09091
Catalytic inositol polyphosphate 5-phosphatase (INPP5c) domain of SH2 domain containing ...
86-376 1.22e-54

Catalytic inositol polyphosphate 5-phosphatase (INPP5c) domain of SH2 domain containing inositol polyphosphate 5-phosphatase-1 and -2, and related proteins; This subfamily contains the INPP5c domain of SHIP1 (SH2 domain containing inositol polyphosphate 5-phosphatase-1, also known as SHIP/INPP5D), and SHIP2 (also known as INPPL1). It belongs to a family of Mg2+-dependent inositol polyphosphate 5-phosphatases, which hydrolyze the 5-phosphate from the inositol ring of various 5-position phosphorylated phosphoinositides (PIs) and inositol phosphates (IPs), and to the large EEP (exonuclease/endonuclease/phosphatase) superfamily that contains functionally diverse enzymes that share a common catalytic mechanism of cleaving phosphodiester bonds. Both SHIP1 and -2 catalyze the dephosphorylation of the PI, phosphatidylinositol 3,4,5-trisphosphate [PI(3,4,5)P3], to phosphatidylinositol 3,4-bisphosphate [PI(3,4)P2]. SHIP1 also converts inositol-1,3,4,5- polyphosphate [I(1,3,4,5)P4] to inositol-1,3,4-polyphosphate [I(1,3,4)P3]. SHIP1 and SHIP2 have little overlap in their in vivo functions. SHIP1 is a negative regulator of cell growth and plays a major part in mediating the inhibitory signaling in B cells; it is predominantly expressed in hematopoietic cells. SHIP2 is as an inhibitor of the insulin signaling pathway, and is implicated in actin structure remodeling, cell adhesion and cell spreading, receptor endocytosis and degradation, and in the JIP1-mediated JNK pathway. SHIP2 is widely expressed, most prominently in brain, heart and in skeletal muscle. In addition to this INPP5c domain, SHIP1 has an N-terminal SH2 domain, two NPXY motifs, and a C-terminal proline-rich region (PRD), while SHIP2 has an N-terminal SH2 domain, a C-terminal proline-rich domain (PRD), which includes a WW-domain binding motif (PPLP), an NPXY motif, and a sterile alpha motif (SAM) domain. The gene encoding SHIP2 is a candidate gene for conferring a predisposition for type 2 diabetes.


Pssm-ID: 197325  Cd Length: 307  Bit Score: 190.16  E-value: 1.22e-54
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2131077827  86 FVGTWNVNGQSPDSELEPWLNC-----------DSNPPDIYCIGFQEldlsteaffyfESVKEQEWSMAVERGLH--SKA 152
Cdd:cd09091     4 FIGTWNMGSAPPPKNITSWFTSkgqgktrddvaDYIPHDIYVIGTQE-----------DPLGEKEWLDLLRHSLKelTSL 72
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2131077827 153 KYKKVQLVRLVGMMLLIFARKDQWQYIRDVATETVGTGIMGKMGNKGGVAVRFVFHNTTFCIVNSHLAAHVEDFERRNQD 232
Cdd:cd09091    73 DYKPIAMQTLWNIRIVVLAKPEHENRISHVCTSSVKTGIANTLGNKGAVGVSFMFNGTSFGFVNSHLTSGSEKKLRRNQN 152
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2131077827 233 YKDICARMSfvVPNQTLPQLNI-MKHDVVIWLGDLNYRLCMP--DANEVKSLINKNDLQRLLKFDQLNIQRTQKKAFADF 309
Cdd:cd09091   153 YLNILRFLS--LGDKKLSAFNItHRFTHLFWLGDLNYRLDLPiqEAENIIQKIEQQQFEPLLRHDQLNLEREEHKVFLRF 230
                         250       260       270       280       290       300       310
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 2131077827 310 TEGEIKFIPTYKYDSKT-DRW-----DSSG-KCRVPAWCDRILWRgtNVNQLH-----YRSHMELKTSDHKPVSALFHI 376
Cdd:cd09091   231 SEEEITFPPTYRYERGSrDTYaytkqKATGvKYNLPSWCDRILWK--SYPETHiicqsYGCTDDIVTSDHSPVFGTFEV 307
INPP5c_SHIP1-INPP5D cd09100
Catalytic inositol polyphosphate 5-phosphatase (INPP5c) domain of SH2 domain containing ...
86-376 5.61e-53

Catalytic inositol polyphosphate 5-phosphatase (INPP5c) domain of SH2 domain containing inositol polyphosphate 5-phosphatase-1 and related proteins; This subfamily contains the INPP5c domain of SHIP1 (SH2 domain containing inositol polyphosphate 5-phosphatase-1, also known as SHIP/INPP5D) and related proteins. It belongs to a family of Mg2+-dependent inositol polyphosphate 5-phosphatases, which hydrolyze the 5-phosphate from the inositol ring of various 5-position phosphorylated phosphoinositides (PIs) and inositol phosphates (IPs), and to the large EEP (exonuclease/endonuclease/phosphatase) superfamily that contains functionally diverse enzymes that share a common catalytic mechanism of cleaving phosphodiester bonds. SHIP1's enzymic activity is restricted to phosphatidylinositol 3,4,5-trisphosphate [PI (3,4,5)P3] and inositol-1,3,4,5- polyphosphate [I(1,3,4,5)P4]. It converts these two phosphoinositides to phosphatidylinositol 3,4-bisphosphate [PI (3,4)P2] and inositol-1,3,4-polyphosphate [I(1,3,4)P3], respectively. SHIP1 is a negative regulator of cell growth and plays a major part in mediating the inhibitory signaling in B cells; it is predominantly expressed in hematopoietic cells. In addition to this INPP5c domain, SHIP1 has an N-terminal SH2 domain, two NPXY motifs, and a C-terminal proline-rich region (PRD). SHIP1's phosphorylated NPXY motifs interact with proteins with phosphotyrosine binding (PTB) domains, and facilitate the translocation of SHIP1 to the plasma membrane to hydrolyze PI(3,4,5)P3. SHIP1 generally acts to oppose the activity of phosphatidylinositol 3-kinase (PI3K). It acts as a negative signaling molecule, reducing the levels of PI(3,4,5)P3, thereby removing the latter as a membrane-targeting signal for PH domain-containing effector molecules. SHIP1 may also, in certain contexts, amplify PI3K signals. SHIP1 and SHIP2 have little overlap in their in vivo functions.


Pssm-ID: 197334  Cd Length: 307  Bit Score: 185.57  E-value: 5.61e-53
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2131077827  86 FVGTWNVNGQSPDSELEPWLNC-----------DSNPPDIYCIGFQELDLSteaffyfesvkEQEWSMAVERGLH--SKA 152
Cdd:cd09100     4 FIGTWNMGNAPPPKKITSWFQCkgqgktrddtaDYIPHDIYVIGTQEDPLG-----------EKEWLDTLKHSLReiTSI 72
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2131077827 153 KYKKVQLVRLVGMMLLIFARKDQWQYIRDVATETVGTGIMGKMGNKGGVAVRFVFHNTTFCIVNSHLAAHVEDFERRNQD 232
Cdd:cd09100    73 SFKVIAIQTLWNIRIVVLAKPEHENRISHICTDSVKTGIANTLGNKGAVGVSFMFNGTSFGFVNSHLTSGSEKKLRRNQN 152
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2131077827 233 YKDIcarMSF-VVPNQTLPQLNIM-KHDVVIWLGDLNYRLCMP--DANEVKSLINKNDLQRLLKFDQLNIQRTQKKAFAD 308
Cdd:cd09100   153 YFNI---LRFlVLGDKKLSPFNIThRFTHLFWLGDLNYRVELPntEAENIIQKIKQQQYQELLPHDQLLIERKESKVFLQ 229
                         250       260       270       280       290       300       310       320
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2131077827 309 FTEGEIKFIPTYKYDSKT-DRW-----DSSG-KCRVPAWCDRILWRgtNVNQLH-----YRSHMELKTSDHKPVSALFHI 376
Cdd:cd09100   230 FEEEEITFAPTYRFERGTrERYaytkqKATGmKYNLPSWCDRVLWK--SYPLVHvvcqsYGCTDDITTSDHSPVFATFEV 307
INPP5c_SHIP2-INPPL1 cd09101
Catalytic inositol polyphosphate 5-phosphatase (INPP5c) domain of SH2 domain containing ...
86-376 4.70e-52

Catalytic inositol polyphosphate 5-phosphatase (INPP5c) domain of SH2 domain containing inositol 5-phosphatase-2 and related proteins; This subfamily contains the INPP5c domain of SHIP2 (SH2 domain containing inositol 5-phosphatase-2, also called INPPL1) and related proteins. It belongs to a family of Mg2+-dependent inositol polyphosphate 5-phosphatases, which hydrolyze the 5-phosphate from the inositol ring of various 5-position phosphorylated phosphoinositides (PIs) and inositol phosphates (IPs), and to the large EEP (exonuclease/endonuclease/phosphatase) superfamily that contains functionally diverse enzymes that share a common catalytic mechanism of cleaving phosphodiester bonds. SHIP2 catalyzes the dephosphorylation of the PI, phosphatidylinositol 3,4,5-trisphosphate [PI(3,4,5)P3], to phosphatidylinositol 3,4-bisphosphate [PI(3,4)P2]. SHIP2 is widely expressed, most prominently in brain, heart and in skeletal muscle. SHIP2 is an inhibitor of the insulin signaling pathway. It is implicated in actin structure remodeling, cell adhesion and cell spreading, receptor endocytosis and degradation, and in the JIP1-mediated JNK pathway. Its interacting partners include filamin/actin, p130Cas, Shc, Vinexin, Interesectin 1, and c-Jun NH2-terminal kinase (JNK)-interacting protein 1 (JIP1). A large variety of extracellular stimuli appear to lead to the tyrosine phosphorylation of SHIP2, including epidermal growth factor (EGF), platelet-derived growth factor (PDGF), insulin, macrophage colony-stimulating factor (M-CSF) and hepatocyte growth factor (HGF). SHIP2 is localized to the cytosol in quiescent cells; following growth factor stimulation and /or cell adhesion, it relocalizes to membrane ruffles. In addition to this INPP5c domain, SHIP2 has an N-terminal SH2 domain, a C-terminal proline-rich domain (PRD), which includes a WW-domain binding motif (PPLP), an NPXY motif and a sterile alpha motif (SAM) domain. The gene encoding SHIP2 is a candidate for conferring a predisposition for type 2 diabetes; it has been suggested that suppression of SHIP2 may be of benefit in the treatment of obesity and thereby prevent type 2 diabetes. SHIP2 and SHIP1 have little overlap in their in vivo functions.


Pssm-ID: 197335  Cd Length: 304  Bit Score: 183.25  E-value: 4.70e-52
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2131077827  86 FVGTWNVNGQSPDSELEPWLNCD-----------SNPPDIYCIGFQEldlsteaffyfESVKEQEWSMAVERGL--HSKA 152
Cdd:cd09101     4 FIGTWNMGSVPPPKSLASWLTSRglgktldettvTIPHDIYVFGTQE-----------NSVGDREWVDFLRASLkeLTDI 72
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2131077827 153 KYKKVQLVRLVGMMLLIFARKDQWQYIRDVATETVGTGIMGKMGNKGGVAVRFVFHNTTFCIVNSHLAAHVEDFERRNQD 232
Cdd:cd09101    73 DYQPIALQCLWNIKMVVLVKPEHENRISHVHTSSVKTGIANTLGNKGAVGVSFMFNGTSFGFVNCHLTSGNEKTHRRNQN 152
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2131077827 233 YKDICARMSfvVPNQTLPQLNI-MKHDVVIWLGDLNYRLCMpDANEVKSLINKNDLQRLLKFDQLNIQRTQKKAFADFTE 311
Cdd:cd09101   153 YLDILRSLS--LGDKQLNAFDIsLRFTHLFWFGDLNYRLDM-DIQEILNYITRKEFDPLLAVDQLNLEREKNKVFLRFRE 229
                         250       260       270       280       290       300       310
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 2131077827 312 GEIKFIPTYKYDSKT------DRWDSSG-KCRVPAWCDRILWRG---TNVNQLHYRSHMELKTSDHKPVSALFHI 376
Cdd:cd09101   230 EEISFPPTYRYERGSrdtymwQKQKTTGmRTNVPSWCDRILWKSypeTHIVCNSYGCTDDIVTSDHSPVFGTFEV 304
INPP5c_INPP5E-like cd09095
Catalytic inositol polyphosphate 5-phosphatase (INPP5c) domain of Inositol ...
81-374 2.81e-50

Catalytic inositol polyphosphate 5-phosphatase (INPP5c) domain of Inositol polyphosphate-5-phosphatase E and related proteins; INPP5c domain of Inositol polyphosphate-5-phosphatase E (also called type IV or 72 kDa 5-phosphatase), rat pharbin, and related proteins. This subfamily belongs to a family of Mg2+-dependent inositol polyphosphate 5-phosphatases, which hydrolyze the 5-phosphate from the inositol ring of various 5-position phosphorylated phosphoinositides (PIs) and inositol phosphates (IPs), and to the large EEP (exonuclease/endonuclease/phosphatase) superfamily that contains functionally diverse enzymes that share a common catalytic mechanism of cleaving phosphodiester bonds. INPP5E hydrolyzes the 5-phosphate from PI(3,5)P2, PI(4,5)P2 and PI(3,4,5)P3, forming PI3P, PI4P, and PI(3,4)P2, respectively. It is a very potent PI(3,4,5)P3 5-phosphatase. Its intracellular localization is chiefly cytosolic, with pronounced perinuclear/Golgi localization. INPP5E also has an N-terminal proline rich domain (PRD) and a C-terminal CAAX motif. This protein is expressed in a variety of tissues, including the breast, brain, testis, and haemopoietic cells. It is differentially expressed in several cancers, for example, it is up-regulated in cervical cancer and down-regulated in stomach cancer. It is a candidate target for therapeutics of obesity and related disorders, as it is expressed in the hypothalamus, and following insulin stimulation, it undergoes tyrosine phosphorylation, associates with insulin receptor substrate-1, -2, and PI3-kinase, and become active as a 5-phosphatase. INPP5E may play a role, along with other 5-phosphatases SHIP2 and SKIP, in regulating glucose homoeostasis and energy metabolism. Mice deficient in INPPE5 develop a multi-organ disorder associated with structural defects of the primary cilium.


Pssm-ID: 197329  Cd Length: 298  Bit Score: 178.00  E-value: 2.81e-50
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2131077827  81 QNFRFFVGTWNVNGQ-SPDSELEPWLNCDSNP--PDIYCIGFQEldlsteaffyfESVKEQEWSMAVERGLhsKAKYKKV 157
Cdd:cd09095     3 RNVGIFVATWNMQGQkELPENLDDFLLPTSADfaQDIYVIGVQE-----------GCSDRREWEIRLQETL--GPSHVLL 69
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2131077827 158 QLVRLVGMMLLIFARKDQWQYIRDVATETVGTGIMGKMGNKGGVAVRFVFHNTTFCIVNSHLAAHVEDFERRNQDYKDIC 237
Cdd:cd09095    70 HSASHGVLHLAVFIRRDLIWFCSEVESATVTTRIVSQIKTKGALAISFTFFGTSFLFITSHFTSGDGKVKERVLDYNKII 149
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2131077827 238 ARMSF--VVPNQTLPQLN---IMKHDVVIWLGDLNYRLCMPdANEVKSLINKN---DLQRLLKFDQLNIQRTQKKAFADF 309
Cdd:cd09095   150 QALNLprNVPTNPYKSESgdvTTRFDEVFWFGDFNFRLSGP-RHLVDALINQGqevDVSALLQHDQLTREMSKGSIFKGF 228
                         250       260       270       280       290       300
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 2131077827 310 TEGEIKFIPTYKYDSKTDRWDSSGKCRVPAWCDRILWRG---TNVNQLHYRSHMELKTSDHKPVSALF 374
Cdd:cd09095   229 QEAPIHFPPTYKFDIGSDVYDTSSKQRVPSYTDRILYRSrqkGDVCCLKYNSCPSIKTSDHRPVFALF 296
PLN03191 PLN03191
Type I inositol-1,4,5-trisphosphate 5-phosphatase 2; Provisional
137-388 4.14e-50

Type I inositol-1,4,5-trisphosphate 5-phosphatase 2; Provisional


Pssm-ID: 215624 [Multi-domain]  Cd Length: 621  Bit Score: 185.88  E-value: 4.14e-50
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2131077827 137 EQEWSMAVERGLHSKAKYKKVQLVRLVGMMLLIFARKDQWQYIRDVATETVGTGIMGKMGNKGGVAVRFVFHNTTFCIVN 216
Cdd:PLN03191  347 YQLPEDLIKDCRKVKQKYVRIVSKQMVGIYVSVWVRKRLRRHINNLKVSPVGVGLMGYMGNKGSVSISMSLFQSRLCFVC 426
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2131077827 217 SHLAAHVEDF--ERRNQDYKDICARMSFV-VPNQTLPQlNIMKHDVVIWLGDLNYRLCMPDAnEVKSLINKNDLQRLLKF 293
Cdd:PLN03191  427 SHLTSGHKDGaeQRRNADVYEIIRRTRFSsVLDTDQPQ-TIPSHDQIFWFGDLNYRLNMLDT-EVRKLVAQKRWDELINS 504
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2131077827 294 DQLNIQRTQKKAFADFTEGEIKFIPTYKYDSKTDRW-----DSSGKCRVPAWCDRILWRGTNVNQLHYRsHMELKTSDHK 368
Cdd:PLN03191  505 DQLIKELRSGHVFDGWKEGPIKFPPTYKYEINSDRYvgenpKEGEKKRSPAWCDRILWLGKGIKQLCYK-RSEIRLSDHR 583
                         250       260
                  ....*....|....*....|
gi 2131077827 369 PVSALFHIGVKVVDERRYRK 388
Cdd:PLN03191  584 PVSSMFLVEVEVFDHRKLQR 603
RhoGAP smart00324
GTPase-activator protein for Rho-like GTPases; GTPase activator proteins towards Rho/Rac ...
576-737 1.17e-39

GTPase-activator protein for Rho-like GTPases; GTPase activator proteins towards Rho/Rac/Cdc42-like small GTPases. etter domain limits and outliers.


Pssm-ID: 214618  Cd Length: 174  Bit Score: 143.95  E-value: 1.17e-39
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2131077827  576 QVPKEIWLLVDHLFKYACHQEDLFQTPGMQEELQQIIDCLDTSIPETIPGSN---HSVAEALLIFLEALPEPVICYELYQ 652
Cdd:smart00324   2 PIPIIVEKCIEYLEKRGLDTEGIYRVSGSKSRVKELRDAFDSGPDPDLDLSEydvHDVAGLLKLFLRELPEPLITYELYE 81
                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2131077827  653 RCLDSAQDP------QNCRQVISQLPRCHRNVFHYLMAFLRELLKFSKYNNVSENMIATLFTSLLLRPPPNLMAR-QTPS 725
Cdd:smart00324  82 EFIEAAKLEdeterlRALRELLSLLPPANRATLRYLLAHLNRVAEHSEENKMTARNLAIVFGPTLLRPPDGEVASlKDIR 161
                          170
                   ....*....|..
gi 2131077827  726 DRQRAIQFLLGF 737
Cdd:smart00324 162 HQNTVIEFLIEN 173
RhoGAP pfam00620
RhoGAP domain; GTPase activator proteins towards Rho/Rac/Cdc42-like small GTPases.
578-716 2.62e-33

RhoGAP domain; GTPase activator proteins towards Rho/Rac/Cdc42-like small GTPases.


Pssm-ID: 459875  Cd Length: 148  Bit Score: 124.96  E-value: 2.62e-33
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2131077827 578 PKEIWLLVDHLFKYACHQEDLFQTPGMQEELQQIIDCLDT--SIPETIPGSN-HSVAEALLIFLEALPEPVICYELYQRC 654
Cdd:pfam00620   1 PLIVRKCVEYLEKRGLDTEGIFRVSGSASRIKELREAFDRgpDVDLDLEEEDvHVVASLLKLFLRELPEPLLTFELYEEF 80
                          90       100       110       120       130       140
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 2131077827 655 LDSAQDP------QNCRQVISQLPRCHRNVFHYLMAFLRELLKFSKYNNVSENMIATLFTSLLLRPPP 716
Cdd:pfam00620  81 IEAAKLPdeeerlEALRELLRKLPPANRDTLRYLLAHLNRVAQNSDVNKMNAHNLAIVFGPTLLRPPD 148
RhoGAP cd00159
RhoGAP: GTPase-activator protein (GAP) for Rho-like GTPases; GAPs towards Rho/Rac/Cdc42-like ...
578-735 9.87e-26

RhoGAP: GTPase-activator protein (GAP) for Rho-like GTPases; GAPs towards Rho/Rac/Cdc42-like small GTPases. Small GTPases (G proteins) cluster into distinct families, and all act as molecular switches, active in their GTP-bound form but inactive when bound to GDP. The Rho family of small G proteins, which includes Cdc42Hs, activates effectors involved in a wide variety of developmental processes, including regulation of cytoskeleton formation, cell proliferation and the JNK signaling pathway. G proteins generally have a low intrinsic GTPase hydrolytic activity but there are family-specific groups of GAPs that enhance the rate of GTP hydrolysis by several orders of magnitude. The RhoGAPs are one of the major classes of regulators of Rho G proteins.


Pssm-ID: 238090 [Multi-domain]  Cd Length: 169  Bit Score: 104.31  E-value: 9.87e-26
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2131077827 578 PKEIWLLVDHLFKYACHQEDLFQTPGMQEELQQIIDCLD--TSIPETIPGSNHSVAEALLIFLEALPEPVICYELYQRCL 655
Cdd:cd00159     1 PLIIEKCIEYLEKNGLNTEGIFRVSGSASKIEELKKKFDrgEDIDDLEDYDVHDVASLLKLYLRELPEPLIPFELYDEFI 80
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2131077827 656 DSAQDP------QNCRQVISQLPRCHRNVFHYLMAFLRELLKFSKYNNVSENMIATLFTSLLLRPPPNLMARQTPSDRQ- 728
Cdd:cd00159    81 ELAKIEdeeeriEALKELLKSLPPENRDLLKYLLKLLHKISQNSEVNKMTASNLAIVFAPTLLRPPDSDDELLEDIKKLn 160

                  ....*..
gi 2131077827 729 RAIQFLL 735
Cdd:cd00159   161 EIVEFLI 167
RhoGAP_FAM13A1a cd04393
RhoGAP_FAM13A1a: RhoGAP (GTPase-activator protein [GAP] for Rho-like small GTPases) domain of ...
564-707 1.14e-13

RhoGAP_FAM13A1a: RhoGAP (GTPase-activator protein [GAP] for Rho-like small GTPases) domain of FAM13A1, isoform a-like proteins. The function of FAM13A1a is unknown. Small GTPases cluster into distinct families, and all act as molecular switches, active in their GTP-bound form but inactive when GDP-bound. The Rho family of GTPases activates effectors involved in a wide variety of developmental processes, including regulation of cytoskeleton formation, cell proliferation and the JNK signaling pathway. GTPases generally have a low intrinsic GTPase hydrolytic activity but there are family-specific groups of GAPs that enhance the rate of GTP hydrolysis by up several orders of magnitude.


Pssm-ID: 239858 [Multi-domain]  Cd Length: 189  Bit Score: 70.18  E-value: 1.14e-13
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2131077827 564 VPLDE----GASERplQVPKEIWLLVDHLFKYACHQEDLFQTPGMQEELQQIIDCLDTSIPETI--PGSNHSVAEALLIF 637
Cdd:cd04393     5 VPLQElqqaGQPEN--GVPAVVRHIVEYLEQHGLEQEGLFRVNGNAETVEWLRQRLDSGEEVDLskEADVCSAASLLRLF 82
                          90       100       110       120       130       140       150
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 2131077827 638 LEALPEPVICYELYQRCLDSAQD-------PQNCRQVISQLPRCHRNVFHYLMAFLRELLKFSKYNNVSENMIATLF 707
Cdd:cd04393    83 LQELPEGLIPASLQIRLMQLYQDyngedefGRKLRDLLQQLPPVNYSLLKFLCHFLSNVASQHHENRMTAENLAAVF 159
RhoGAP_nadrin cd04386
RhoGAP_nadrin: RhoGAP (GTPase-activator protein [GAP] for Rho-like small GTPases) domain of ...
564-715 5.43e-13

RhoGAP_nadrin: RhoGAP (GTPase-activator protein [GAP] for Rho-like small GTPases) domain of Nadrin-like proteins. Nadrin, also named Rich-1, has been shown to be involved in the regulation of Ca2+-dependent exocytosis in neurons and recently has been implicated in tight junction maintenance in mammalian epithelium. Small GTPases cluster into distinct families, and all act as molecular switches, active in their GTP-bound form but inactive when GDP-bound. The Rho family of GTPases activates effectors involved in a wide variety of developmental processes, including regulation of cytoskeleton formation, cell proliferation and the JNK signaling pathway. GTPases generally have a low intrinsic GTPase hydrolytic activity but there are family-specific groups of GAPs that enhance the rate of GTP hydrolysis by several orders of magnitude.


Pssm-ID: 239851  Cd Length: 203  Bit Score: 68.64  E-value: 5.43e-13
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2131077827 564 VPLDE--GASERPLQVPKEiwLLVDHLFKYACHQEDLFQTPGMQEELQQIIDCLD--TSIPETIPGSN--HSVAEALLIF 637
Cdd:cd04386     7 TPLEEhlKRTGREIALPIE--ACVMCLLETGMNEEGLFRVGGGASKLKRLKAALDagTFSLPLDEFYSdpHAVASALKSY 84
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2131077827 638 LEALPEPVICYELYQRCLDSAQDP------QNCRQVISQLPRCHRNVFHYLMAFLRELLKFSKYNNVSENMIATLFTSLL 711
Cdd:cd04386    85 LRELPDPLLTYNLYEDWVQAANKPdederlQAIWRILNKLPRENRDNLRYLIKFLSKLAQKSDENKMSPSNIAIVLAPNL 164

                  ....
gi 2131077827 712 LRPP 715
Cdd:cd04386   165 LWAK 168
RhoGAP_ARHGAP22_24_25 cd04390
RhoGAP_ARHGAP22_24_25: GTPase-activator protein (GAP) domain for Rho-like GTPases found in ...
574-724 2.77e-11

RhoGAP_ARHGAP22_24_25: GTPase-activator protein (GAP) domain for Rho-like GTPases found in ARHGAP22, 24 and 25-like proteins; longer isoforms of these proteins contain an additional N-terminal pleckstrin homology (PH) domain. ARHGAP25 (KIA0053) has been identified as a GAP for Rac1 and Cdc42. Short isoforms (without the PH domain) of ARHGAP24, called RC-GAP72 and p73RhoGAP, and of ARHGAP22, called p68RacGAP, has been shown to be involved in angiogenesis and endothelial cell capillary formation. Small GTPases cluster into distinct families, and all act as molecular switches, active in their GTP-bound form but inactive when GDP-bound. The Rho family of GTPases activates effectors involved in a wide variety of developmental processes, including regulation of cytoskeleton formation, cell proliferation and the JNK signaling pathway. GTPases generally have a low intrinsic GTPase hydrolytic activity but there are family-specific groups of GAPs that enhance the rate of GTP hydrolysis by several orders of magnitude.


Pssm-ID: 239855 [Multi-domain]  Cd Length: 199  Bit Score: 63.23  E-value: 2.77e-11
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2131077827 574 PLQVPKEIWLLVDHLFKYACHQEDLFQTPGMQEELQQIIDCLDTSIPETIPGSN--HSVAEALLIFLEALPEPVICYELY 651
Cdd:cd04390    19 PRLVPILVEQCVDFIREHGLKEEGLFRLPGQANLVKQLQDAFDAGERPSFDSDTdvHTVASLLKLYLRELPEPVIPWAQY 98
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2131077827 652 QRCLDSAQ--------DPQNCRQVISQLPRCHRNVFHYLMAFLRELLKFSKYNNVSENMIATLFTSLLLRP----PPNLM 719
Cdd:cd04390    99 EDFLSCAQllskdeekGLGELMKQVSILPKVNYNLLSYICRFLDEVQSNSSVNKMSVQNLATVFGPNILRPkvedPATIM 178

                  ....*
gi 2131077827 720 ARQTP 724
Cdd:cd04390   179 EGTPQ 183
RhoGAP_KIAA1688 cd04389
RhoGAP_KIAA1688: GTPase-activator protein (GAP) domain for Rho-like GTPases found in ...
575-701 3.99e-10

RhoGAP_KIAA1688: GTPase-activator protein (GAP) domain for Rho-like GTPases found in KIAA1688-like proteins; KIAA1688 is a protein of unknown function that contains a RhoGAP domain and a myosin tail homology 4 (MyTH4) domain. Small GTPases cluster into distinct families, and all act as molecular switches, active in their GTP-bound form but inactive when GDP-bound. The Rho family of GTPases activates effectors involved in a wide variety of developmental processes, including regulation of cytoskeleton formation, cell proliferation and the JNK signaling pathway. GTPases generally have a low intrinsic GTPase hydrolytic activity but there are family-specific groups of GAPs that enhance the rate of GTP hydrolysis by several orders of magnitude.


Pssm-ID: 239854  Cd Length: 187  Bit Score: 59.71  E-value: 3.99e-10
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2131077827 575 LQVPKEIWLLVDHLFKYACHQ-EDLFQTPGMQEELQQIIDCLDT-SIPETIPGSNHSVAEALLIFLEALPEPVICYELYQ 652
Cdd:cd04389    19 LKLPWILTFLSEKVLALGGFQtEGIFRVPGDIDEVNELKLRVDQwDYPLSGLEDPHVPASLLKLWLRELEEPLIPDALYQ 98
                          90       100       110       120
                  ....*....|....*....|....*....|....*....|....*....
gi 2131077827 653 RCLDSAQDPQNCRQVISQLPRCHRNVFHYLMAFLREllkFSKYNNVSEN 701
Cdd:cd04389    99 QCISASEDPDKAVEIVQKLPIINRLVLCYLINFLQV---FAQPENVAHT 144
RhoGAP-p50rhoGAP cd04404
RhoGAP-p50rhoGAP: RhoGAP (GTPase-activator protein [GAP] for Rho-like small GTPases) domain of ...
628-719 7.81e-10

RhoGAP-p50rhoGAP: RhoGAP (GTPase-activator protein [GAP] for Rho-like small GTPases) domain of p50RhoGAP-like proteins; p50RhoGAP, also known as RhoGAP-1, contains a C-terminal RhoGAP domain and an N-terminal Sec14 domain which binds phosphatidylinositol 3,4,5-trisphosphate (PtdIns(3,4,5)P3). It is ubiquitously expressed and preferentially active on Cdc42. This subgroup also contains closely related ARHGAP8. Small GTPases cluster into distinct families, and all act as molecular switches, active in their GTP-bound form but inactive when GDP-bound. The Rho family of GTPases activates effectors involved in a wide variety of developmental processes, including regulation of cytoskeleton formation, cell proliferation and the JNK signaling pathway. GTPases generally have a low intrinsic GTPase hydrolytic activity but there are family-specific groups of GAPs that enhance the rate of GTP hydrolysis by several orders of magnitude.


Pssm-ID: 239869 [Multi-domain]  Cd Length: 195  Bit Score: 58.89  E-value: 7.81e-10
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2131077827 628 HSVAEALLIFLEALPEPVICYELYQRC-----LDSAQDPQNCRQVISQLPRCHRNVFHYLMAFLRELLKFSKYNNVSENM 702
Cdd:cd04404    76 HLPAVILKTFLRELPEPLLTFDLYDDIvgflnVDKEERVERVKQLLQTLPEENYQVLKYLIKFLVQVSAHSDQNKMTNSN 155
                          90
                  ....*....|....*..
gi 2131077827 703 IATLFTSLLLRPPPNLM 719
Cdd:cd04404   156 LAVVFGPNLLWAKDASM 172
RhoGAP_chimaerin cd04372
RhoGAP_chimaerin: RhoGAP (GTPase-activator protein [GAP] for Rho-like small GTPases) domain of ...
595-715 9.44e-10

RhoGAP_chimaerin: RhoGAP (GTPase-activator protein [GAP] for Rho-like small GTPases) domain of chimaerins. Chimaerins are a family of phorbolester- and diacylglycerol-responsive GAPs specific for the Rho-like GTPase Rac. Chimaerins exist in two alternative splice forms that each contain a C-terminal GAP domain, and a central C1 domain which binds phorbol esters, inducing a conformational change that activates the protein; one splice form is lacking the N-terminal Src homology-2 (SH2) domain. Small GTPases cluster into distinct families, and all act as molecular switches, active in their GTP-bound form but inactive when GDP-bound. The Rho family of GTPases activates effectors involved in a wide variety of developmental processes, including regulation of cytoskeleton formation, cell proliferation and the JNK signaling pathway. GTPases generally have a low intrinsic GTPase hydrolytic activity but there are family-specific groups of GAPs that enhance the rate of GTP hydrolysis by several orders of magnitude.


Pssm-ID: 239837 [Multi-domain]  Cd Length: 194  Bit Score: 58.68  E-value: 9.44e-10
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2131077827 595 QEDLFQTPGMQEELQQIIDCLD-----TSIPETIPGSNHSVAEALLIFLEALPEPVICYELYQRCLDSAQDP------QN 663
Cdd:cd04372    34 SEGLYRVSGFAEEIEDVKMAFDrdgekADISATVYPDINVITGALKLYFRDLPIPVITYDTYPKFIDAAKISnpderlEA 113
                          90       100       110       120       130
                  ....*....|....*....|....*....|....*....|....*....|..
gi 2131077827 664 CRQVISQLPRCHRNVFHYLMAFLRELLKFSKYNNVSENMIATLFTSLLLRPP 715
Cdd:cd04372   114 VHEALMLLPPAHYETLRYLMEHLKRVTLHEKDNKMNAENLGIVFGPTLMRPP 165
RhoGAP_GMIP_PARG1 cd04378
RhoGAP_GMIP_PARG1: RhoGAP (GTPase-activator protein [GAP] for Rho-like small GTPases) domain ...
626-716 1.03e-09

RhoGAP_GMIP_PARG1: RhoGAP (GTPase-activator protein [GAP] for Rho-like small GTPases) domain of GMIP (Gem interacting protein) and PARG1 (PTPL1-associated RhoGAP1). GMIP plays important roles in neurite growth and axonal guidance, and interacts with Gem, a member of the RGK subfamily of the Ras small GTPase superfamily, through the N-terminal half of the protein. GMIP contains a C-terminal RhoGAP domain. GMIP inhibits RhoA function, but is inactive towards Rac1 and Cdc41. PARG1 interacts with Rap2, also a member of the Ras small GTPase superfamily whose exact function is unknown, and shows strong preference for Rho. Small GTPases cluster into distinct families, and all act as molecular switches, active in their GTP-bound form but inactive when GDP-bound. The Rho family of GTPases activates effectors involved in a wide variety of developmental processes, including regulation of cytoskeleton formation, cell proliferation and the JNK signaling pathway. GTPases generally have a low intrinsic GTPase hydrolytic activity but there are family-specific groups of GAPs that enhance the rate of GTP hydrolysis by several orders of magnitude.


Pssm-ID: 239843  Cd Length: 203  Bit Score: 58.97  E-value: 1.03e-09
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2131077827 626 SNHSVAEALLIFLEALPEPVICYELYQRCLDSAQDPQN--------------------CRQVISQLPRCHRNVFHYLMAF 685
Cdd:cd04378    67 SPHDISSVLKLFLRQLPEPLILFRLYNDFIALAKEIQRdteedkapntpievnriirkLKDLLRQLPASNYNTLQHLIAH 146
                          90       100       110
                  ....*....|....*....|....*....|.
gi 2131077827 686 LRELLKFSKYNNVSENMIATLFTSLLLRPPP 716
Cdd:cd04378   147 LYRVAEQFEENKMSPNNLGIVFGPTLIRPRP 177
EEP cd08372
Exonuclease-Endonuclease-Phosphatase (EEP) domain superfamily; This large superfamily includes ...
87-370 4.62e-09

Exonuclease-Endonuclease-Phosphatase (EEP) domain superfamily; This large superfamily includes the catalytic domain (exonuclease/endonuclease/phosphatase or EEP domain) of a diverse set of proteins including the ExoIII family of apurinic/apyrimidinic (AP) endonucleases, inositol polyphosphate 5-phosphatases (INPP5), neutral sphingomyelinases (nSMases), deadenylases (such as the vertebrate circadian-clock regulated nocturnin), bacterial cytolethal distending toxin B (CdtB), deoxyribonuclease 1 (DNase1), the endonuclease domain of the non-LTR retrotransposon LINE-1, and related domains. These diverse enzymes share a common catalytic mechanism of cleaving phosphodiester bonds; their substrates range from nucleic acids to phospholipids and perhaps proteins.


Pssm-ID: 197306 [Multi-domain]  Cd Length: 241  Bit Score: 57.49  E-value: 4.62e-09
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2131077827  87 VGTWNVNGQSPDSELEPWL-NCDSNPPDIYCIgfQELDLSTeAFFYFESVKEQEWSMAVERGLHSKAKYKKVqlvrlvgm 165
Cdd:cd08372     1 VASYNVNGLNAATRASGIArWVRELDPDIVCL--QEVKDSQ-YSAVALNQLLPEGYHQYQSGPSRKEGYEGV-------- 69
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2131077827 166 mlLIFARKDQWqyirDVATETVGTGIMGKMGNKGGVAVRFVFHNTTFCIVNSHLAAhvedfERRNQDYKDICARMsFVvp 245
Cdd:cd08372    70 --AILSKTPKF----KIVEKHQYKFGEGDSGERRAVVVKFDVHDKELCVVNAHLQA-----GGTRADVRDAQLKE-VL-- 135
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2131077827 246 nQTLPQLNIMKHDVVIWLGDLNYRlcmpdanevKSLInknDLQRLLKFDQLNIQRTQKKAFADFTegeikFIPTYKYDSK 325
Cdd:cd08372   136 -EFLKRLRQPNSAPVVICGDFNVR---------PSEV---DSENPSSMLRLFVALNLVDSFETLP-----HAYTFDTYMH 197
                         250       260       270       280       290
                  ....*....|....*....|....*....|....*....|....*....|
gi 2131077827 326 tdrwdssgkcRVPAWCDRILWRGT---NV--NQLHYRSHMELKTSDHKPV 370
Cdd:cd08372   198 ----------NVKSRLDYIFVSKSllpSVksSKILSDAARARIPSDHYPI 237
RhoGAP_myosin_IX cd04377
RhoGAP_myosin_IX: RhoGAP (GTPase-activator protein [GAP] for Rho-like small GTPases) domain ...
564-726 1.51e-08

RhoGAP_myosin_IX: RhoGAP (GTPase-activator protein [GAP] for Rho-like small GTPases) domain present in class IX myosins. Class IX myosins contain a characteristic head domain, a neck domain, a tail domain which contains a C6H2-zinc binding motif and a RhoGAP domain. Class IX myosins are single-headed, processive myosins that are partly cytoplasmic, and partly associated with membranes and the actin cytoskeleton. Class IX myosins are implicated in the regulation of neuronal morphogenesis and function of sensory systems, like the inner ear. There are two major isoforms, myosin IXA and IXB with several splice variants, which are both expressed in developing neurons. Small GTPases cluster into distinct families, and all act as molecular switches, active in their GTP-bound form but inactive when GDP-bound. The Rho family of GTPases activates effectors involved in a wide variety of developmental processes, including regulation of cytoskeleton formation, cell proliferation and the JNK signaling pathway. GTPases generally have a low intrinsic GTPase hydrolytic activity but there are family-specific groups of GAPs that enhance the rate of GTP hydrolysis by several orders of magnitude.


Pssm-ID: 239842  Cd Length: 186  Bit Score: 55.14  E-value: 1.51e-08
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2131077827 564 VPLDEGASERPlQVPKEIWLLVDHLFKYACHQEDLFQTPGMQEELQQIIDCLDTSiPETIPGSN---HSVAEALLIFLEA 640
Cdd:cd04377     3 VSLSSLTSEDR-SVPLVLEKLLEHIEMHGLYTEGIYRKSGSANKIKELRQGLDTD-PDSVNLEDypiHVITSVLKQWLRE 80
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2131077827 641 LPEPVICYELYQRCLDSA--QDPQNCRQ----VISQLPRCHRNVFHYLMAFLRELLKFSKYNNVSENMIATLFTSLLLRP 714
Cdd:cd04377    81 LPEPLMTFELYENFLRAMelEEKQERVRalysVLEQLPRANLNTLERLIFHLVRVALQEEVNRMSANALAIVFAPCILRC 160
                         170
                  ....*....|..
gi 2131077827 715 PPNLMARQTPSD 726
Cdd:cd04377   161 PDTADPLQSLQD 172
RhoGAP_ARHGAP6 cd04376
RhoGAP_ARHGAP6: RhoGAP (GTPase-activator protein [GAP] for Rho-like small GTPases) domain of ...
575-732 1.62e-08

RhoGAP_ARHGAP6: RhoGAP (GTPase-activator protein [GAP] for Rho-like small GTPases) domain of ArhGAP6-like proteins. ArhGAP6 shows GAP activity towards RhoA, but not towards Cdc42 and Rac1. ArhGAP6 is often deleted in microphthalmia with linear skin defects syndrome (MLS); MLS is a severe X-linked developmental disorder. Small GTPases cluster into distinct families, and all act as molecular switches, active in their GTP-bound form but inactive when GDP-bound. The Rho family of GTPases activates effectors involved in a wide variety of developmental processes, including regulation of cytoskeleton formation, cell proliferation and the JNK signaling pathway. GTPases generally have a low intrinsic GTPase hydrolytic activity but there are family-specific groups of GAPs that enhance the rate of GTP hydrolysis by several orders of magnitude.


Pssm-ID: 239841  Cd Length: 206  Bit Score: 55.52  E-value: 1.62e-08
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2131077827 575 LQVPKEIWLLVDHLFKYACHQEDLFQTPGMQEELQQI---IDC-LDTSIPETIpgSNHSVAEALLIFLEALPEPVICYEL 650
Cdd:cd04376     7 RQVPRLVESCCQHLEKHGLQTVGIFRVGSSKKRVRQLreeFDRgIDVVLDENH--SVHDVAALLKEFFRDMPDPLLPREL 84
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2131077827 651 YQRCLDSA-----QDPQNCRQVISQLPRCHRNVFHYLMAFLRELLKFSKY-----------NNVSENMIATLFTslllrp 714
Cdd:cd04376    85 YTAFIGTAllepdEQLEALQLLIYLLPPCNCDTLHRLLKFLHTVAEHAADsidedgqevsgNKMTSLNLATIFG------ 158
                         170
                  ....*....|....*...
gi 2131077827 715 pPNLMARQTPSDRQRAIQ 732
Cdd:cd04376   159 -PNLLHKQKSGEREFVQA 175
RhoGAP_myosin_IXB cd04407
RhoGAP_myosin_IXB: RhoGAP (GTPase-activator protein [GAP] for Rho-like small GTPases) domain ...
577-717 2.26e-08

RhoGAP_myosin_IXB: RhoGAP (GTPase-activator protein [GAP] for Rho-like small GTPases) domain present in myosins IXB. Class IX myosins contain a characteristic head domain, a neck domain and a tail domain which contains a C6H2-zinc binding motif and a Rho-GAP domain. Class IX myosins are single-headed, processive myosins that are partly cytoplasmic, and partly associated with membranes and the actin cytoskeleton. Class IX myosins are implicated in the regulation of neuronal morphogenesis and function of sensory systems, like the inner ear. There are two major isoforms, myosin IXA and IXB with several splice variants, which are both expressed in developing neurons Small GTPases cluster into distinct families, and all act as molecular switches, active in their GTP-bound form but inactive when GDP-bound. The Rho family of GTPases activates effectors involved in a wide variety of developmental processes, including regulation of cytoskeleton formation, cell proliferation and the JNK signaling pathway. GTPases generally have a low intrinsic GTPase hydrolytic activity but there are family-specific groups of GAPs that enhance the rate of GTP hydrolysis by several orders of magnitude.


Pssm-ID: 239872 [Multi-domain]  Cd Length: 186  Bit Score: 54.61  E-value: 2.26e-08
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2131077827 577 VPKEIWLLVDHLFKYACHQEDLFQTPGMQEELQQIIDCLDTSiPETIPGSN---HSVAEALLIFLEALPEPVICYELYQR 653
Cdd:cd04407    15 VPIVLEKLLEHVEMHGLYTEGIYRKSGSANRMKELHQLLQAD-PENVKLENypiHAITGLLKQWLRELPEPLMTFAQYND 93
                          90       100       110       120       130       140       150
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2131077827 654 CLDSAQDPQNCRQ------VISQLPRCHRNVFHYLMAFLRELLKFSKYNNVSENMIATLFTSLLLRPPPN 717
Cdd:cd04407    94 FLRAVELPEKQEQlqaiyrVLEQLPTANHNTLERLIFHLVKVALEEDVNRMSPNALAIVFAPCLLRCPDS 163
RhoGAP_srGAP cd04383
RhoGAP_srGAP: RhoGAP (GTPase-activator protein [GAP] for Rho-like small GTPases) domain ...
579-717 6.27e-08

RhoGAP_srGAP: RhoGAP (GTPase-activator protein [GAP] for Rho-like small GTPases) domain present in srGAPs. srGAPs are components of the intracellular part of Slit-Robo signalling pathway that is important for axon guidance and cell migration. srGAPs contain an N-terminal FCH domain, a central RhoGAP domain and a C-terminal SH3 domain; this SH3 domain interacts with the intracellular proline-rich-tail of the Roundabout receptor (Robo). This interaction with Robo then activates the rhoGAP domain which in turn inhibits Cdc42 activity. Small GTPases cluster into distinct families, and all act as molecular switches, active in their GTP-bound form but inactive when GDP-bound. The Rho family of GTPases activates effectors involved in a wide variety of developmental processes, including regulation of cytoskeleton formation, cell proliferation and the JNK signaling pathway. GTPases generally have a low intrinsic GTPase hydrolytic activity but there are family-specific groups of GAPs that enhance the rate of GTP hydrolysis by several orders of magnitude.


Pssm-ID: 239848  Cd Length: 188  Bit Score: 53.19  E-value: 6.27e-08
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2131077827 579 KEIWLLVDHLFKYAC----HQEDLFQTPGMQEELQQIIDCLDT-SIPETIPGSNH---SVAEALLIFLEALPEPVICYEL 650
Cdd:cd04383    16 QAIPLVVESCIRFINlyglQHQGIFRVSGSQVEVNDIKNAFERgEDPLADDQNDHdinSVAGVLKLYFRGLENPLFPKER 95
                          90       100       110       120       130       140       150
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|...
gi 2131077827 651 YQRCLDSAQ--DPQ----NCRQVISQLPRCHRNVFHYLMAFLRELLKFSKYNNVSENMIATLFTSLLLRPPPN 717
Cdd:cd04383    96 FEDLMSCVKleNPTervhQIREILSTLPRSVIIVMRYLFAFLNHLSQFSDENMMDPYNLAICFGPTLMPVPEG 168
RhoGAP_GMIP cd04408
RhoGAP_GMIP: RhoGAP (GTPase-activator protein [GAP] for Rho-like small GTPases) domain of GMIP ...
626-716 7.23e-08

RhoGAP_GMIP: RhoGAP (GTPase-activator protein [GAP] for Rho-like small GTPases) domain of GMIP (Gem interacting protein). GMIP plays important roles in neurite growth and axonal guidance, and interacts with Gem, a member of the RGK subfamily of the Ras small GTPase superfamily, through the N-terminal half of the protein. GMIP contains a C-terminal RhoGAP domain. GMIP inhibits RhoA function, but is inactive towards Rac1 and Cdc41. Small GTPases cluster into distinct families, and all act as molecular switches, active in their GTP-bound form but inactive when GDP-bound. The Rho family of GTPases activates effectors involved in a wide variety of developmental processes, including regulation of cytoskeleton formation, cell proliferation and the JNK signaling pathway. GTPases generally have a low intrinsic GTPase hydrolytic activity but there are family-specific groups of GAPs that enhance the rate of GTP hydrolysis by several orders of magnitude.


Pssm-ID: 239873  Cd Length: 200  Bit Score: 53.28  E-value: 7.23e-08
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2131077827 626 SNHSVAEALLIFLEALPEPVICYELYQRCL--------DSAQDP----------QNCRQVISQLPRCHRNVFHYLMAFLR 687
Cdd:cd04408    67 SPHDITSVLKHFLKELPEPVLPFQLYDDFIalakelqrDSEKAAespsiveniiRSLKELLGRLPVSNYNTLRHLMAHLY 146
                          90       100
                  ....*....|....*....|....*....
gi 2131077827 688 ELLKFSKYNNVSENMIATLFTSLLLRPPP 716
Cdd:cd04408   147 RVAERFEDNKMSPNNLGIVFGPTLLRPLV 175
INPP5A cd09092
Type I inositol polyphosphate 5-phosphatase I; Type I inositol polyphosphate 5-phosphatase I ...
194-376 6.38e-07

Type I inositol polyphosphate 5-phosphatase I; Type I inositol polyphosphate 5-phosphatase I (INPP5A) hydrolyzes the 5-phosphate from inositol 1,3,4,5-tetrakisphosphate [I(1,3,4,5)P4] and inositol 1,4,5-trisphosphate [I(1,4,5)P3]. It belongs to a family of Mg2+-dependent inositol polyphosphate 5-phosphatases, which hydrolyze the 5-phosphate from the inositol ring of various 5-position phosphorylated phosphoinositides (PIs) and inositol phosphates (IPs), and to the large EEP (exonuclease/endonuclease/phosphatase) superfamily that contains functionally diverse enzymes that share a common catalytic mechanism of cleaving phosphodiester bonds. As the substrates of INPP5A mobilize intracellular calcium ions, INPP5A is a calcium signal-terminating enzyme. In platelets, phosphorylated pleckstrin binds and activates INPP5A in a 1:1 complex, and accelerates the degradation of the calcium ion-mobilizing I(1,4,5)P3.


Pssm-ID: 197326  Cd Length: 383  Bit Score: 52.47  E-value: 6.38e-07
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2131077827 194 KMGNKGGVAVRFVFHNTTFCIVNSHL---AAHVEDFERRNQDYKDICAR-MSFV---VPNQTLPQLNImkhdvvIWLGDL 266
Cdd:cd09092   151 KWSRKGFMRTRWKINNCVFDLVNIHLfhdASNLAACESSPSVYSQNRHRaLGYVlerLTDERFEKVPF------FVFGDF 224
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2131077827 267 NYR---------LCM---------PDANEVKSLIN---------------------------KNDLQRLLKFDQlniqrt 301
Cdd:cd09092   225 NFRldtksvvetLCAkatmqtvrkADSNIVVKLEFrekdndnkvvlqiekkkfdyfnqdvfrDNNGKALLKFDK------ 298
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2131077827 302 QKKAFAD-FTEGEIKFIPTYKYDSKTDRWDSSGKCRVPAWCDRILWrGTNVNQLH---------YRS-HMELKTSDHKPV 370
Cdd:cd09092   299 ELEVFKDvLYELDISFPPSYPYSEDPEQGTQYMNTRCPAWCDRILM-SHSARELKseneeksvtYDMiGPNVCMGDHKPV 377

                  ....*.
gi 2131077827 371 SALFHI 376
Cdd:cd09092   378 FLTFRI 383
RhoGAP_myosin_IXA cd04406
RhoGAP_myosin_IXA: RhoGAP (GTPase-activator protein [GAP] for Rho-like small GTPases) domain ...
577-726 1.62e-06

RhoGAP_myosin_IXA: RhoGAP (GTPase-activator protein [GAP] for Rho-like small GTPases) domain present in myosins IXA. Class IX myosins contain a characteristic head domain, a neck domain and a tail domain which contains a C6H2-zinc binding motif and a Rho-GAP domain. Class IX myosins are single-headed, processive myosins that are partly cytoplasmic, and partly associated with membranes and the actin cytoskeleton. Class IX myosins are implicated in the regulation of neuronal morphogenesis and function of sensory systems, like the inner ear. There are two major isoforms, myosin IXA and IXB with several splice variants, which are both expressed in developing neurons. Small GTPases cluster into distinct families, and all act as molecular switches, active in their GTP-bound form but inactive when GDP-bound. The Rho family of GTPases activates effectors involved in a wide variety of developmental processes, including regulation of cytoskeleton formation, cell proliferation and the JNK signaling pathway. GTPases generally have a low intrinsic GTPase hydrolytic activity but there are family-specific groups of GAPs that enhance the rate of GTP hydrolysis by several orders of magnitude.


Pssm-ID: 239871  Cd Length: 186  Bit Score: 49.23  E-value: 1.62e-06
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2131077827 577 VPKEIWLLVDHLFKYACHQEDLFQTPGMQEELQQIIDCLDTSIPET-IPGSN-HSVAEALLIFLEALPEPVICYELYQRC 654
Cdd:cd04406    15 VPLVVEKLINYIEMHGLYTEGIYRKSGSTNKIKELRQGLDTDANSVnLDDYNiHVIASVFKQWLRDLPNPLMTFELYEEF 94
                          90       100       110       120       130       140       150
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 2131077827 655 L------DSAQDPQNCRQVISQLPRCHRNVFHYLMAFLRELLKFSKYNNVSENMIATLFTSLLLRPPPNLMARQTPSD 726
Cdd:cd04406    95 LramglqERRETVRGVYSVIDQLSRTHLNTLERLIFHLVRIALQEETNRMSANALAIVFAPCILRCPDTTDPLQSVQD 172
RhoGAP_Bcr cd04387
RhoGAP_Bcr: RhoGAP (GTPase-activator protein [GAP] for Rho-like small GTPases) domain of Bcr ...
576-739 2.29e-06

RhoGAP_Bcr: RhoGAP (GTPase-activator protein [GAP] for Rho-like small GTPases) domain of Bcr (breakpoint cluster region protein)-like proteins. Bcr is a multidomain protein with a variety of enzymatic functions. It contains a RhoGAP and a Rho GEF domain, a Ser/Thr kinase domain, an N-terminal oligomerization domain, and a C-terminal PDZ binding domain, in addition to PH and C2 domains. Bcr is a negative regulator of: i) RacGTPase, via the Rho GAP domain, ii) the Ras-Raf-MEK-ERK pathway, via phosphorylation of the Ras binding protein AF-6, and iii) the Wnt signaling pathway through binding beta-catenin. Bcr can form a complex with beta-catenin and Tcf1. The Wnt signaling pathway is involved in cell proliferation, differentiation, and cell renewal. Bcr was discovered as a fusion partner of Abl. The Bcr-Abl fusion is characteristic for a large majority of chronic myelogenous leukemias (CML). Small GTPases cluster into distinct families, and all act as molecular switches, active in their GTP-bound form but inactive when GDP-bound. The Rho family of GTPases activates effectors involved in a wide variety of developmental processes, including regulation of cytoskeleton formation, cell proliferation and the JNK signaling pathway. GTPases generally have a low intrinsic GTPase hydrolytic activity but there are family-specific groups of GAPs that enhance the rate of GTP hydrolysis by several orders of magnitude.


Pssm-ID: 239852 [Multi-domain]  Cd Length: 196  Bit Score: 48.77  E-value: 2.29e-06
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2131077827 576 QVPKEIWLLVDHLFKYACHQEDLFQTPGMQEELQQIIDCLDTSIPETIPGSN----HSVAEALLIFLEALPEPVICYELY 651
Cdd:cd04387    15 KVPYIVRQCVEEVERRGMEEVGIYRISGVATDIQALKAAFDTNNKDVSVMLSemdvNAIAGTLKLYFRELPEPLFTDELY 94
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2131077827 652 QRCLD--SAQDP---QNCR-QVISQLPRCHRNVFHYLMAFLRELLKFSKYNNVSENMIATLFTSLLLRP-------PPNL 718
Cdd:cd04387    95 PNFAEgiALSDPvakESCMlNLLLSLPDPNLVTFLFLLHHLKRVAEREEVNKMSLHNLATVFGPTLLRPsekeskiPTNT 174
                         170       180
                  ....*....|....*....|.
gi 2131077827 719 MARQTPSDRQRAIQFLLGFLE 739
Cdd:cd04387   175 MTDSWSLEVMSQVQVLLYFLQ 195
RhoGAP_CdGAP cd04384
RhoGAP_CdGAP: RhoGAP (GTPase-activator protein [GAP] for Rho-like small GTPases) domain of ...
628-716 4.39e-06

RhoGAP_CdGAP: RhoGAP (GTPase-activator protein [GAP] for Rho-like small GTPases) domain of CdGAP-like proteins; CdGAP contains an N-terminal RhoGAP domain and a C-terminal proline-rich region, and it is active on both Cdc42 and Rac1 but not RhoA. CdGAP is recruited to focal adhesions via the interaction with the scaffold protein actopaxin (alpha-parvin). Small GTPases cluster into distinct families, and all act as molecular switches, active in their GTP-bound form but inactive when GDP-bound. The Rho family of GTPases activates effectors involved in a wide variety of developmental processes, including regulation of cytoskeleton formation, cell proliferation and the JNK signaling pathway. GTPases generally have a low intrinsic GTPase hydrolytic activity but there are family-specific groups of GAPs that enhance the rate of GTP hydrolysis by several orders of magnitude.


Pssm-ID: 239849 [Multi-domain]  Cd Length: 195  Bit Score: 47.88  E-value: 4.39e-06
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2131077827 628 HSVAEALLIFLEALPEPVICYELYQRCLDSAQ-DPQN-----CRQVISQLPRCHRNVFHYLMAFLRELLKFSKYNNVSEN 701
Cdd:cd04384    73 HSVSSLCKLYFRELPNPLLTYQLYEKFSEAVSaASDEerlekIHDVIQQLPPPHYRTLEFLMRHLSRLAKYCSITNMHAK 152
                          90
                  ....*....|....*
gi 2131077827 702 MIATLFTSLLLRPPP 716
Cdd:cd04384   153 NLAIVWAPNLLRSKQ 167
RhoGAP_p85 cd04388
RhoGAP_p85: RhoGAP (GTPase-activator protein [GAP] for Rho-like small GTPases) domain present ...
600-716 1.07e-05

RhoGAP_p85: RhoGAP (GTPase-activator protein [GAP] for Rho-like small GTPases) domain present in the p85 isoforms of the regulatory subunit of the class IA PI3K (phosphatidylinositol 3'-kinase). This domain is also called Bcr (breakpoint cluster region protein) homology (BH) domain. Class IA PI3Ks are heterodimers, containing a regulatory subunit (p85) and a catalytic subunit (p110) and are activated by growth factor receptor tyrosine kinases (RTKs); this activation is mediated by the p85 subunit. p85 isoforms, alpha and beta, contain a C-terminal p110-binding domain flanked by two SH2 domains, an N-terminal SH3 domain, and a RhoGAP domain flanked by two proline-rich regions. Small GTPases cluster into distinct families, and all act as molecular switches, active in their GTP-bound form but inactive when GDP-bound. The Rho family of GTPases activates effectors involved in a wide variety of developmental processes, including regulation of cytoskeleton formation, cell proliferation and the JNK signaling pathway. GTPases generally have a low intrinsic GTPase hydrolytic activity but there are family-specific groups of GAPs that enhance the rate of GTP hydrolysis by several orders of magnitude.


Pssm-ID: 239853  Cd Length: 200  Bit Score: 46.79  E-value: 1.07e-05
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2131077827 600 QTPGMQEELQQIIDClDTSIPETIPGSNHSVAEALLIFLEALPEPVICYELYQRCLDSAQDPQN---CRQVISQLPRCHR 676
Cdd:cd04388    40 QSSSSLTELRQILDC-DAASVDLEQFDVAALADALKRYLLDLPNPVIPAPVYSEMISRAQEVQSsdeYAQLLRKLIRSPN 118
                          90       100       110       120
                  ....*....|....*....|....*....|....*....|....*..
gi 2131077827 677 NVFHYLMAfLRELLKF-------SKYNNVSENMIATLFTSLLLRPPP 716
Cdd:cd04388   119 LPHQYWLT-LQYLLKHffrlcqsSSKNLLSARALAEIFSPLLFRFQP 164
RhoGAP_p190 cd04373
RhoGAP_p190: RhoGAP (GTPase-activator protein [GAP] for Rho-like small GTPases) domain of ...
564-714 1.15e-05

RhoGAP_p190: RhoGAP (GTPase-activator protein [GAP] for Rho-like small GTPases) domain of p190-like proteins. p190, also named RhoGAP5, plays a role in neuritogenesis and axon branch stability. p190 shows a preference for Rho, over Rac and Cdc42, and consists of an N-terminal GTPase domain and a C-terminal GAP domain. The central portion of p190 contains important regulatory phosphorylation sites. Small GTPases cluster into distinct families, and all act as molecular switches, active in their GTP-bound form but inactive when GDP-bound. The Rho family of GTPases activates effectors involved in a wide variety of developmental processes, including regulation of cytoskeleton formation, cell proliferation and the JNK signaling pathway. GTPases generally have a low intrinsic GTPase hydrolytic activity but there are family-specific groups of GAPs that enhance the rate of GTP hydrolysis by several orders of magnitude.


Pssm-ID: 239838  Cd Length: 185  Bit Score: 46.68  E-value: 1.15e-05
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2131077827 564 VPL-DEGASERPlqVPKEIWLLVDHLFKYACHQEDLFQTPGMQEELQQI-----------IDCLDTSIpetipgsnHSVA 631
Cdd:cd04373     3 VPLaNVVTSEKP--IPIFLEKCVEFIEATGLETEGIYRVSGNKTHLDSLqkqfdqdhnldLVSKDFTV--------NAVA 72
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2131077827 632 EALLIFLEALPEPVICYELYQRCL------DSAQDPQNCRQVISQLPRCHRNVFHYLMAFLRELLKFSKYNNVSENMIAT 705
Cdd:cd04373    73 GALKSFFSELPDPLIPYSMHLELVeaakinDREQRLHALKELLKKFPPENFDVFKYVITHLNKVSQNSKVNLMTSENLSI 152

                  ....*....
gi 2131077827 706 LFTSLLLRP 714
Cdd:cd04373   153 CFWPTLMRP 161
RhoGAP_ARHGAP20 cd04402
RhoGAP_ARHGAP20: RhoGAP (GTPase-activator protein [GAP] for Rho-like small GTPases) domain of ...
577-735 1.69e-05

RhoGAP_ARHGAP20: RhoGAP (GTPase-activator protein [GAP] for Rho-like small GTPases) domain of ArhGAP20-like proteins. ArhGAP20, also known as KIAA1391 and RA-RhoGAP, contains a RhoGAP, a RA, and a PH domain, and ANXL repeats. ArhGAP20 is activated by Rap1 and induces inactivation of Rho, which in turn leads to neurite outgrowth. Small GTPases cluster into distinct families, and all act as molecular switches, active in their GTP-bound form but inactive when GDP-bound. The Rho family of GTPases activates effectors involved in a wide variety of developmental processes, including regulation of cytoskeleton formation, cell proliferation and the JNK signaling pathway. GTPases generally have a low intrinsic GTPase hydrolytic activity but there are family-specific groups of GAPs that enhance the rate of GTP hydrolysis by several orders of magnitude.


Pssm-ID: 239867  Cd Length: 192  Bit Score: 46.14  E-value: 1.69e-05
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2131077827 577 VPKEIWLLVDHLFKYACHQEDLFQTPGMQEELQQIIDCLDTSI-PETIPGSNHSVAEALLIFLEALPEPVICYELYQRCL 655
Cdd:cd04402    15 LPKPILDMLSLLYQKGPSTEGIFRRSANAKACKELKEKLNSGVeVDLKAEPVLLLASVLKDFLRNIPGSLLSSDLYEEWM 94
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2131077827 656 DSAQDPQN------CRQVISQLPRCHrnvfhylMAFLRELLKFskYNNVSEN-----MIAtlfTSLLLRPPPNLMARQTP 724
Cdd:cd04402    95 SALDQENEeekiaeLQRLLDKLPRPN-------VLLLKHLICV--LHNISQNsetnkMDA---FNLAVCIAPSLLWPPAS 162
                         170
                  ....*....|....*....
gi 2131077827 725 SDRQRA--------IQFLL 735
Cdd:cd04402   163 SELQNEdlkkvtslVQFLI 181
RhoGAP_fRGD1 cd04398
RhoGAP_fRGD1: RhoGAP (GTPase-activator protein [GAP] for Rho-like small GTPases) domain of ...
564-735 4.54e-05

RhoGAP_fRGD1: RhoGAP (GTPase-activator protein [GAP] for Rho-like small GTPases) domain of fungal RGD1-like proteins. Yeast Rgd1 is a GAP protein for Rho3 and Rho4 and plays a role in low-pH response. Small GTPases cluster into distinct families, and all act as molecular switches, active in their GTP-bound form but inactive when GDP-bound. The Rho family of GTPases activates effectors involved in a wide variety of developmental processes, including regulation of cytoskeleton formation, cell proliferation and the JNK signaling pathway. GTPases generally have a low intrinsic GTPase hydrolytic activity but there are family-specific groups of GAPs that enhance the rate of GTP hydrolysis by several orders of magnitude.


Pssm-ID: 239863  Cd Length: 192  Bit Score: 45.09  E-value: 4.54e-05
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2131077827 564 VPLDEGASERPLQVPKEIWLLVDHLFKYACHQEDLFQTPGMQEELQQIIDCLDT--SIPETIPGSN-----HSVAEALLI 636
Cdd:cd04398     3 VPLEDLILREGDNVPNIVYQCIQAIENFGLNLEGIYRLSGNVSRVNKLKELFDKdpLNVLLISPEDyesdiHSVASLLKL 82
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2131077827 637 FLEALPEPVICYELYQRCLDSAQ--DPQNCR----QVISQLPRCHRNVFHYLMAFLRELLKFSKYNNVSENMIATLFTSL 710
Cdd:cd04398    83 FFRELPEPLLTKALSREFIEAAKieDESRRRdalhGLINDLPDANYATLRALMFHLARIKEHESVNRMSVNNLAIIWGPT 162
                         170       180
                  ....*....|....*....|....*...
gi 2131077827 711 LLR-PPPNL--MARQTpsdrqRAIQFLL 735
Cdd:cd04398   163 LMNaAPDNAadMSFQS-----RVIETLL 185
RhoGAP_fLRG1 cd04397
RhoGAP_fLRG1: RhoGAP (GTPase-activator protein [GAP] for Rho-like small GTPases) domain of ...
567-742 6.72e-05

RhoGAP_fLRG1: RhoGAP (GTPase-activator protein [GAP] for Rho-like small GTPases) domain of fungal LRG1-like proteins. Yeast Lrg1p is required for efficient cell fusion, and mother-daughter cell separation, possibly through acting as a RhoGAP specifically regulating 1,3-beta-glucan synthesis. Small GTPases cluster into distinct families, and all act as molecular switches, active in their GTP-bound form but inactive when GDP-bound. The Rho family of GTPases activates effectors involved in a wide variety of developmental processes, including regulation of cytoskeleton formation, cell proliferation and the JNK signaling pathway. GTPases generally have a low intrinsic GTPase hydrolytic activity but there are family-specific groups of GAPs that enhance the rate of GTP hydrolysis by several orders of magnitude.


Pssm-ID: 239862  Cd Length: 213  Bit Score: 44.66  E-value: 6.72e-05
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2131077827 567 DEGASERPLQVPKEIWLLVDHLFKYACHQEDLFQTPGMQEELQQIIDCLDTSiPETIP--GSNHSVAEALLI--FLEALP 642
Cdd:cd04397    17 TLGVGPGKLRIPALIDDIISAMRQMDMSVEGVFRKNGNIRRLKELTEEIDKN-PTEVPdlSKENPVQLAALLkkFLRELP 95
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2131077827 643 EPVICYELYQRCLDSAQ--DPQNCRQVI----SQLPRCHRNVFHYLMAFLRELLKFSKYNNVSEN-M----IATLFTSLL 711
Cdd:cd04397    96 DPLLTFKLYRLWISSQKieDEEERKRVLhlvyCLLPKYHRDTMEVLFSFLKWVSSFSHIDEETGSkMdihnLATVITPNI 175
                         170       180       190
                  ....*....|....*....|....*....|.
gi 2131077827 712 LRPPPNlmARQTPSDRQRAIQFLLGFLESDE 742
Cdd:cd04397   176 LYSKTD--NPNTGDEYFLAIEAVNYLIENNE 204
RhoGAP_ARHGAP19 cd04392
RhoGAP_ARHGAP19: RhoGAP (GTPase-activator protein [GAP] for Rho-like small GTPases) domain of ...
575-736 7.66e-05

RhoGAP_ARHGAP19: RhoGAP (GTPase-activator protein [GAP] for Rho-like small GTPases) domain of ArhGAP19-like proteins. The function of ArhGAP19 is unknown. Small GTPases cluster into distinct families, and all act as molecular switches, active in their GTP-bound form but inactive when GDP-bound. The Rho family of GTPases activates effectors involved in a wide variety of developmental processes, including regulation of cytoskeleton formation, cell proliferation and the JNK signaling pathway. GTPases generally have a low intrinsic GTPase hydrolytic activity but there are family-specific groups of GAPs that enhance the rate of GTP hydrolysis by several orders of magnitude.


Pssm-ID: 239857  Cd Length: 208  Bit Score: 44.37  E-value: 7.66e-05
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2131077827 575 LQVPKEIWLLVDHLfkyacHQEDLFQTPG---MQEELQQIIDClDTSIP-ETIPGSNHSVAEALLIFLEALPEPVICYEL 650
Cdd:cd04392    11 AQIYQLIEYLEKNL-----RVEGLFRKPGnsaRQQELRDLLNS-GTDLDlESGGFHAHDCATVLKGFLGELPEPLLTHAH 84
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2131077827 651 YQRCL------------DSAQDPQNCRQVISQ------LPRCHRNVFHYLMAFLRELLKFSKYNNVSENMIATLFTSLLL 712
Cdd:cd04392    85 YPAHLqiadlcqfdekgNKTSAPDKERLLEALqlllllLPEENRNLLKLILDLLYQTAKHEDKNKMSADNLALLFTPHLI 164
                         170       180
                  ....*....|....*....|....
gi 2131077827 713 RPppnlmARQTPSDRQRAIQFLLG 736
Cdd:cd04392   165 CP-----RNLTPEDLHENAQKLNS 183
RhoGAP_MgcRacGAP cd04382
RhoGAP_MgcRacGAP: RhoGAP (GTPase-activator protein [GAP] for Rho-like small GTPases) domain ...
594-737 1.63e-04

RhoGAP_MgcRacGAP: RhoGAP (GTPase-activator protein [GAP] for Rho-like small GTPases) domain present in MgcRacGAP proteins. MgcRacGAP plays an important dual role in cytokinesis: i) it is part of centralspindlin-complex, together with the mitotic kinesin MKLP1, which is critical for the structure of the central spindle by promoting microtuble bundling. ii) after phosphorylation by aurora B MgcRacGAP becomes an effective regulator of RhoA and plays an important role in the assembly of the contractile ring and the initiation of cytokinesis. MgcRacGAP-like proteins contain a N-terminal C1-like domain, and a C-terminal RhoGAP domain. Small GTPases cluster into distinct families, and all act as molecular switches, active in their GTP-bound form but inactive when GDP-bound. The Rho family of GTPases activates effectors involved in a wide variety of developmental processes, including regulation of cytoskeleton formation, cell proliferation and the JNK signaling pathway. GTPases generally have a low intrinsic GTPase hydrolytic activity but there are family-specific groups of GAPs that enhance the rate of GTP hydrolysis by several orders of magnitude.


Pssm-ID: 239847  Cd Length: 193  Bit Score: 43.44  E-value: 1.63e-04
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2131077827 594 HQEDLFQTPGMQEELQQIIDCLDTSipETIPGSN----HSVAEALLIFLEALPEPVICYELYQRCLDSAQ--DPQNCR-- 665
Cdd:cd04382    34 TEEGLYRVSGSEREVKALKEKFLRG--KTVPNLSkvdiHVICGCLKDFLRSLKEPLITFALWKEFMEAAEilDEDNSRaa 111
                          90       100       110       120       130       140       150
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 2131077827 666 --QVISQLPRCHRNVFHYLMAFLRELLKfSKYNNVSENMIA-----TLFTSLLLRPPPNLMARQTPsDRQRAIQFLLGF 737
Cdd:cd04382   112 lyQAISELPQPNRDTLAFLILHLQRVAQ-SPECKMDINNLArvfgpTIVGYSVPNPDPMTILQDTV-RQPRVVERLLEI 188
RhoGAP_SYD1 cd04379
RhoGAP_SYD1: RhoGAP (GTPase-activator protein [GAP] for Rho-like small GTPases) domain present ...
620-714 1.81e-04

RhoGAP_SYD1: RhoGAP (GTPase-activator protein [GAP] for Rho-like small GTPases) domain present in SYD-1_like proteins. Syd-1, first identified and best studied in C.elegans, has been shown to play an important role in neuronal development by specifying axonal properties. Small GTPases cluster into distinct families, and all act as molecular switches, active in their GTP-bound form but inactive when GDP-bound. The Rho family of GTPases activates effectors involved in a wide variety of developmental processes, including regulation of cytoskeleton formation, cell proliferation and the JNK signaling pathway. GTPases generally have a low intrinsic GTPase hydrolytic activity but there are family-specific groups of GAPs that enhance the rate of GTP hydrolysis by several orders of magnitude.


Pssm-ID: 239844  Cd Length: 207  Bit Score: 43.22  E-value: 1.81e-04
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2131077827 620 PETIPGSNhSVAEALLIFLEALPEPVICYELYQRCLDSA-----QDPQNCRQ----VISQLPRCHRNVFHYLMAFLRELL 690
Cdd:cd04379    67 EELYPDIN-VITGVLKDYLRELPEPLITPQLYEMVLEALavalpNDVQTNTHltlsIIDCLPLSAKATLLLLLDHLSLVL 145
                          90       100
                  ....*....|....*....|....
gi 2131077827 691 KFSKYNNVSENMIATLFTSLLLRP 714
Cdd:cd04379   146 SNSERNKMTPQNLAVCFGPVLMFC 169
RhoGAP_fBEM3 cd04400
RhoGAP_fBEM3: RhoGAP (GTPase-activator [GAP] protein for Rho-like small GTPases) domain of ...
628-719 2.74e-04

RhoGAP_fBEM3: RhoGAP (GTPase-activator [GAP] protein for Rho-like small GTPases) domain of fungal BEM3-like proteins. Bem3 is a GAP protein of Cdc42, and is specifically involved in the control of the initial assembly of the septin ring in yeast bud formation. Small GTPases cluster into distinct families, and all act as molecular switches, active in their GTP-bound form but inactive when GDP-bound. The Rho family of GTPases activates effectors involved in a wide variety of developmental processes, including regulation of cytoskeleton formation, cell proliferation and the JNK signaling pathway. GTPases generally have a low intrinsic GTPase hydrolytic activity but there are family-specific groups of GAPs that enhance the rate of GTP hydrolysis by several orders of magnitude.


Pssm-ID: 239865 [Multi-domain]  Cd Length: 190  Bit Score: 42.73  E-value: 2.74e-04
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2131077827 628 HSVAEALLIFLEALPEPVICYELY---QRCLDSAQDPQN----CRQVISQLPRCHRNVFHYLMAFLRELLKFSKYNNVSE 700
Cdd:cd04400    79 HTVAGLLKLYLRELPTLILGGELHndfKRLVEENHDRSQraleLKDLVSQLPQANYDLLYVLFSFLRKIIEHSDVNKMNL 158
                          90
                  ....*....|....*....
gi 2131077827 701 NMIATLFTSLLLRPPPNLM 719
Cdd:cd04400   159 RNVCIVFSPTLNIPAGIFV 177
RhoGAP_ARAP cd04385
RhoGAP_ARAP: RhoGAP (GTPase-activator protein [GAP] for Rho-like small GTPases) domain present ...
628-714 4.93e-04

RhoGAP_ARAP: RhoGAP (GTPase-activator protein [GAP] for Rho-like small GTPases) domain present in ARAPs. ARAPs (also known as centaurin deltas) contain, besides the RhoGAP domain, an Arf GAP, ankyrin repeat ras-associating, and PH domains. Since their ArfGAP activity is PIP3-dependent, ARAPs are considered integration points for phosphoinositide, Arf and Rho signaling. Small GTPases cluster into distinct families, and all act as molecular switches, active in their GTP-bound form but inactive when GDP-bound. The Rho family of GTPases activates effectors involved in a wide variety of developmental processes, including regulation of cytoskeleton formation, cell proliferation and the JNK signaling pathway. GTPases generally have a low intrinsic GTPase hydrolytic activity but there are family-specific groups of GAPs that enhance the rate of GTP hydrolysis by several orders of magnitude.


Pssm-ID: 239850  Cd Length: 184  Bit Score: 41.91  E-value: 4.93e-04
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2131077827 628 HSVAEALLIFLEALPEPVICYELYQRCLDSAQDPQNC------RQVISQLPRCHRNVFHYLMAFLRELLKFSKYNNVSEN 701
Cdd:cd04385    70 HDVADVLKRFLRDLPDPLLTSELHAEWIEAAELENKDeriaryKELIRRLPPINRATLKVLIGHLYRVQKHSDENQMSVH 149
                          90
                  ....*....|...
gi 2131077827 702 MIATLFTSLLLRP 714
Cdd:cd04385   150 NLALVFGPTLFQT 162
RhoGAP_DLC1 cd04375
RhoGAP_DLC1: RhoGAP (GTPase-activator protein [GAP] for Rho-like small GTPases) domain of ...
577-708 9.93e-04

RhoGAP_DLC1: RhoGAP (GTPase-activator protein [GAP] for Rho-like small GTPases) domain of DLC1-like proteins. DLC1 shows in vitro GAP activity towards RhoA and CDC42. Beside its C-terminal GAP domain, DLC1 also contains a SAM (sterile alpha motif) and a START (StAR-related lipid transfer action) domain. DLC1 has tumor suppressor activity in cell culture. Small GTPases cluster into distinct families, and all act as molecular switches, active in their GTP-bound form but inactive when GDP-bound. The Rho family of GTPases activates effectors involved in a wide variety of developmental processes, including regulation of cytoskeleton formation, cell proliferation and the JNK signaling pathway. GTPases generally have a low intrinsic GTPase hydrolytic activity but there are family-specific groups of GAPs that enhance the rate of GTP hydrolysis by several orders of magnitude.


Pssm-ID: 239840  Cd Length: 220  Bit Score: 41.25  E-value: 9.93e-04
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2131077827 577 VPKEIWLLVDHLFKYACHQEDLFQTPGMQEELQQIIDCLDTSIPETIPGSNHS--VAEALLIFLEALPEPVICYEL---- 650
Cdd:cd04375    20 LPRSIQQAMRWLRNNALDQVGLFRKSGVKSRIQKLRSMIESSTDNVNYDGQQAydVADMLKQYFRDLPEPLLTNKLsetf 99
                          90       100       110       120       130       140
                  ....*....|....*....|....*....|....*....|....*....|....*....|.
gi 2131077827 651 ---YQRcLDSAQDPQNCRQVISQLPRCHRNVFHYLMAFLRELLKFSKYNNVSENMIATLFT 708
Cdd:cd04375   100 iaiFQY-VPKEQRLEAVQCAILLLPDENREVLQTLLYFLSDVAANSQENQMTATNLAVCLA 159
RhoGAP_ARHGAP21 cd04395
RhoGAP_ARHGAP21: RhoGAP (GTPase-activator protein [GAP] for Rho-like small GTPases) domain of ...
628-720 1.38e-03

RhoGAP_ARHGAP21: RhoGAP (GTPase-activator protein [GAP] for Rho-like small GTPases) domain of ArhGAP21-like proteins. ArhGAP21 is a multi-domain protein, containing RhoGAP, PH and PDZ domains, and is believed to play a role in the organization of the cell-cell junction complex. It has been shown to function as a GAP of Cdc42 and RhoA, and to interact with alpha-catenin and Arf6. Small GTPases cluster into distinct families, and all act as molecular switches, active in their GTP-bound form but inactive when GDP-bound. The Rho family of GTPases activates effectors involved in a wide variety of developmental processes, including regulation of cytoskeleton formation, cell proliferation and the JNK signaling pathway. GTPases generally have a low intrinsic GTPase hydrolytic activity but there are family-specific groups of GAPs that enhance the rate of GTP hydrolysis by several orders of magnitude.


Pssm-ID: 239860  Cd Length: 196  Bit Score: 40.46  E-value: 1.38e-03
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2131077827 628 HSVAEALLIFLEALPEPVICYELYQRCLDS--AQDPQN----CRQVISQLPRCHRNVFHYLMAFLRELLKFSKYNNVSEN 701
Cdd:cd04395    74 NVVSSLLKSFFRKLPEPLFTNELYPDFIEAnrIEDPVErlkeLRRLIHSLPDHHYETLKHLIRHLKTVADNSEVNKMEPR 153
                          90
                  ....*....|....*....
gi 2131077827 702 MIATLFTSLLLRPPPNLMA 720
Cdd:cd04395   154 NLAIVFGPTLVRTSDDNME 172
RhoGap_RalBP1 cd04381
RhoGap_RalBP1: RhoGAP (GTPase-activator protein [GAP] for Rho-like small GTPases) domain ...
564-706 3.93e-03

RhoGap_RalBP1: RhoGAP (GTPase-activator protein [GAP] for Rho-like small GTPases) domain present in RalBP1 proteins, also known as RLIP, RLIP76 or cytocentrin. RalBP1 plays an important role in endocytosis during interphase. During mitosis, RalBP1 transiently associates with the centromere and has been shown to play an essential role in the proper assembly of the mitotic apparatus. RalBP1 is an effector of the Ral GTPase which itself is an effector of Ras. RalBP1 contains a RhoGAP domain, which shows weak activity towards Rac1 and Cdc42, but not towards Ral, and a Ral effector domain binding motif. Small GTPases cluster into distinct families, and all act as molecular switches, active in their GTP-bound form but inactive when GDP-bound. The Rho family of GTPases activates effectors involved in a wide variety of developmental processes, including regulation of cytoskeleton formation, cell proliferation and the JNK signaling pathway. GTPases generally have a low intrinsic GTPase hydrolytic activity but there are family-specific groups of GAPs that enhance the rate of GTP hydrolysis by several orders of magnitude.


Pssm-ID: 239846 [Multi-domain]  Cd Length: 182  Bit Score: 38.96  E-value: 3.93e-03
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2131077827 564 VPLDEgASERP-----LQVPKEIWLLVDHLFKYACHQEDLFQTPGMQEELQQIIDCLD----TSIPETIPgsnHSVAEAL 634
Cdd:cd04381     3 ASLSL-AVERSrchdgIDLPLVFRECIDYVEKHGMKCEGIYKVSGIKSKVDELKAAYNrresPNLEEYEP---PTVASLL 78
                          90       100       110       120       130       140       150
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 2131077827 635 LIFLEALPEPVICYELYQR------CLDSAQDPQNCRQVISQLPRCHRNVFHYLMAFLRELLKFSKYNNVSENMIATL 706
Cdd:cd04381    79 KQYLRELPEPLLTKELMPRfeeacgRPTEAEREQELQRLLKELPECNRLLLAWLIVHMDHVIAQELETKMNIQNISIV 156
RhoGAP-ARHGAP11A cd04394
RhoGAP-ARHGAP11A: RhoGAP (GTPase-activator protein [GAP] for Rho-like small GTPases) domain of ...
584-729 4.35e-03

RhoGAP-ARHGAP11A: RhoGAP (GTPase-activator protein [GAP] for Rho-like small GTPases) domain of ArhGAP11A-like proteins. The mouse homolog of human ArhGAP11A has been detected as a gene exclusively expressed in immature ganglion cells, potentially playing a role in retinal development. The exact function of ArhGAP11A is unknown. Small GTPases cluster into distinct families, and all act as molecular switches, active in their GTP-bound form but inactive when GDP-bound. The Rho family of GTPases activates effectors involved in a wide variety of developmental processes, including regulation of cytoskeleton formation, cell proliferation and the JNK signaling pathway. GTPases generally have a low intrinsic GTPase hydrolytic activity but there are family-specific groups of GAPs that enhance the rate of GTP hydrolysis by several orders of magnitude.


Pssm-ID: 239859 [Multi-domain]  Cd Length: 202  Bit Score: 38.99  E-value: 4.35e-03
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2131077827 584 LVDHLfkyacHQEDLFQTPG---MQEELQQIID----CLDTSIPEtipgsnhSVAEALLIFLEALPEPVICYELYQRCLD 656
Cdd:cd04394    31 LLDHL-----STEGLFRKSGsvvRQKELKAKLEggeaCLSSALPC-------DVAGLLKQFFRELPEPLLPYDLHEALLK 98
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2131077827 657 SAQDPQNcRQVISQ-------LPRCHRNVFHYLMAFLRELLKFSKYNNVSENMIATLFTSLLLrPPPNLMARQTPSDRQR 729
Cdd:cd04394    99 AQELPTD-EERKSAtllltclLPDEHVNTLRYFFSFLYDVAQRCSENKMDSSNLAVIFAPNLF-QSEEGGEKMSSSTEKR 176
RhoGAP_Graf cd04374
RhoGAP_Graf: GTPase-activator protein (GAP) domain for Rho-like GTPases found in GRAF (GTPase ...
594-714 9.05e-03

RhoGAP_Graf: GTPase-activator protein (GAP) domain for Rho-like GTPases found in GRAF (GTPase regulator associated with focal adhesion kinase); Graf is a multi-domain protein, containing SH3 and PH domains, that binds focal adhesion kinase and influences cytoskeletal changes mediated by Rho proteins. Graf exhibits GAP activity toward RhoA and Cdc42, but only weakly activates Rac1. Small GTPases cluster into distinct families, and all act as molecular switches, active in their GTP-bound form but inactive when GDP-bound. The Rho family of GTPases activates effectors involved in a wide variety of developmental processes, including regulation of cytoskeleton formation, cell proliferation and the JNK signaling pathway. GTPases generally have a low intrinsic GTPase hydrolytic activity but there are family-specific groups of GAPs that enhance the rate of GTP hydrolysis by several orders of magnitude.


Pssm-ID: 239839  Cd Length: 203  Bit Score: 38.14  E-value: 9.05e-03
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2131077827 594 HQEDLFQTPGMQEELQQII---------DCLDTSIPETIPGSNhSVAEALLIFLEALPEPVICYELYQRCLDSA-QDPQN 663
Cdd:cd04374    45 NEQGLYRVVGVNSKVQKLLslgldpktsTPGDVDLDNSEWEIK-TITSALKTYLRNLPEPLMTYELHNDFINAAkSENLE 123
                          90       100       110       120       130
                  ....*....|....*....|....*....|....*....|....*....|....*.
gi 2131077827 664 CR-----QVISQLPRCHRNVFHYLMAFLRELLKFSKYNNVSENMIATLFTSLLLRP 714
Cdd:cd04374   124 SRvnaihSLVHKLPEKNREMLELLIKHLTNVSDHSKKNLMTVSNLGVVFGPTLLRP 179
 
Blast search parameters
Data Source: Precalculated data, version = cdd.v.3.21
Preset Options:Database: CDSEARCH/cdd   Low complexity filter: no  Composition Based Adjustment: yes   E-value threshold: 0.01

References:

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