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Conserved domains on  [gi|1907204050|ref|XP_036017879|]
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inositol polyphosphate 5-phosphatase OCRL isoform X6 [Mus musculus]

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 ...
 9-300 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: 583.12  E-value: 0e+00
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907204050   9 FFVGTWNVNGQSPDSSLEPWLDCDPNPPDIYCIGFQELDLSTEAFFYFESVKEQEWSLAVERGLPSKAKYRKVQLVRLVG 88
Cdd:cd09093     3 IFVGTWNVNGQSPDESLRPWLSCDEEPPDIYAIGFQELDLSAEAFLFNDSSREQEWVKAVERGLHPDAKYKKVKLIRLVG 82

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907204050  89 MMLLIFARKDQCQYIRDVATETTGTGIMGKMGNKGGVAVRFVFHNTTFCIVNSHLAAHVEEFERRNQDYKDICARMTFSV 168
Cdd:cd09093    83 MMLLVFVKKEHRQHIKEVAAETVGTGIMGKMGNKGGVAVRFQFHNTTFCFVNSHLAAHMEEVERRNQDYKDICARMKFED 162

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907204050 169 PNQtvPQVNIMKHDVVIWLGDLNYRLCMPDASEVKSLINKNELHKLLKFDQLNIQRTQKKAFADFNEGEINFVPTYKYDS 248
Cdd:cd09093   163 PDG--PPLSISDHDVVFWLGDLNYRIQELPTEEVKELIEKNDLEELLKYDQLNIQRRAGKVFEGFTEGEINFIPTYKYDP 240

                         250       260       270       280       290
                  ....*....|....*....|....*....|....*....|....*....|..
gi 1907204050 249 KTDRWDSSGKCRVPAWCDRILWRGINVNQLHYRSHMELKTSDHKPVSALFHI 300
Cdd:cd09093   241 GTDNWDSSEKCRAPAWCDRILWRGTNIVQLSYRSHMELKTSDHKPVSALFDI 292
RhoGAP_OCRL1 cd04380
RhoGAP_OCRL1: RhoGAP (GTPase-activator protein [GAP] for Rho-like small GTPases) domain ...
 435-663 4.99e-86

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: 268.83  E-value: 4.99e-86
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907204050 435 FLTIGGNYLPSCFGTSLEALCRMKRPIREVPVTKLIDLEEDSYlekeksllqmvpldegtSERPLQVPKEIWLLVDHLFK 514
Cdd:cd04380     1 FITVTGVYLPSCFGSSLETLIRLPDPGIRNLIDQLELGDNPDY-----------------SEVPLSIPKEIWRLVDYLYT 63

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907204050 515 YACHQEDLFQTPGMQEE----LQQIIDCLDTSIPETIPGNNHSVAEALLIFLEALPEPVICYELYQRCLDS-AHDPRICK 589
Cdd:cd04380    64 RGLAQEGLFEEPGLPSEpgelLAEIRDALDTGSPFNSPGSAESVAEALLLFLESLPDPIIPYSLYERLLEAvANNEEDKR 143

                         170       180       190       200       210       220       230
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 1907204050 590 QVIS-QLPRCHRNVFRYLMAFLRELLKFSDYNNINTNMIATLFSSLLLRPPPNLMTRQTPNDRQHAIQFLLVFLL 663
Cdd:cd04380   144 QVIRiSLPPVHRNVFVYLCSFLRELLSESADRGLDENTLATIFGRVLLRDPPRAGGKERRAERDRKRAFIEQFLL 218
 
Name Accession Description Interval E-value
INPP5c_INPP5B cd09093
Catalytic inositol polyphosphate 5-phosphatase (INPP5c) domain of Type II inositol ...
 9-300 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: 583.12  E-value: 0e+00
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907204050   9 FFVGTWNVNGQSPDSSLEPWLDCDPNPPDIYCIGFQELDLSTEAFFYFESVKEQEWSLAVERGLPSKAKYRKVQLVRLVG 88
Cdd:cd09093     3 IFVGTWNVNGQSPDESLRPWLSCDEEPPDIYAIGFQELDLSAEAFLFNDSSREQEWVKAVERGLHPDAKYKKVKLIRLVG 82

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907204050  89 MMLLIFARKDQCQYIRDVATETTGTGIMGKMGNKGGVAVRFVFHNTTFCIVNSHLAAHVEEFERRNQDYKDICARMTFSV 168
Cdd:cd09093    83 MMLLVFVKKEHRQHIKEVAAETVGTGIMGKMGNKGGVAVRFQFHNTTFCFVNSHLAAHMEEVERRNQDYKDICARMKFED 162

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907204050 169 PNQtvPQVNIMKHDVVIWLGDLNYRLCMPDASEVKSLINKNELHKLLKFDQLNIQRTQKKAFADFNEGEINFVPTYKYDS 248
Cdd:cd09093   163 PDG--PPLSISDHDVVFWLGDLNYRIQELPTEEVKELIEKNDLEELLKYDQLNIQRRAGKVFEGFTEGEINFIPTYKYDP 240

                         250       260       270       280       290
                  ....*....|....*....|....*....|....*....|....*....|..
gi 1907204050 249 KTDRWDSSGKCRVPAWCDRILWRGINVNQLHYRSHMELKTSDHKPVSALFHI 300
Cdd:cd09093   241 GTDNWDSSEKCRAPAWCDRILWRGTNIVQLSYRSHMELKTSDHKPVSALFDI 292
IPPc smart00128
Inositol polyphosphate phosphatase, catalytic domain homologues; Mg(2+)-dependent/Li(+) ...
 9-303 3.63e-126

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


Pssm-ID: 214525 [Multi-domain]  Cd Length: 306  Bit Score: 375.54  E-value: 3.63e-126
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907204050    9 FFVGTWNVNGQS-PDSSLEPWLDC-----DPNPPDIYCIGFQELDLSTE-AFFYFESVKEQEWSLAVERGLPSKAKYRKV 81
Cdd:smart00128   5 VLIGTWNVGGLEsPKVDVTSWLFQkievkQSEKPDIYVIGLQEVVGLAPgVILETIAGKERLWSDLLESSLNGDGQYNVL 84

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907204050   82 QLVRLVGMMLLIFARKDQCQYIRDVATETTGTGIMGKMGNKGGVAVRFVFHNTTFCIVNSHLAAHVEEFERRNQDYKDIC 161
Cdd:smart00128  85 AKVYLVGILVLVFVKANHLVYIKDVETFTVKTGMGGLWGNKGAVAVRFKLSDTSFCFVNSHLAAGASNVEQRNQDYKTIL 164

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907204050  162 ARMTFSVPnqtvPQVNIMKHDVVIWLGDLNYRLCMPDASEVKSLINKNELHKLLKFDQLNIQRTQKKAFADFNEGEINFV 241
Cdd:smart00128 165 RALSFPER----ALLSQFDHDVVFWFGDLNFRLDSPSYEEVRRKISKKEFDDLLEKDQLNRQREAGKVFKGFQEGPITFP 240

                          250       260       270       280       290       300
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 1907204050  242 PTYKYDS-KTDRWDSSGKCRVPAWCDRILWR--GINVNQL-HYRSHMELKTSDHKPVSALFHIGVK 303
Cdd:smart00128 241 PTYKYDSvGTETYDTSEKKRVPAWCDRILYRsnGPELIQLsEYHSGMEITTSDHKPVFATFRLKVT 306
RhoGAP_OCRL1 cd04380
RhoGAP_OCRL1: RhoGAP (GTPase-activator protein [GAP] for Rho-like small GTPases) domain ...
 435-663 4.99e-86

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: 268.83  E-value: 4.99e-86
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907204050 435 FLTIGGNYLPSCFGTSLEALCRMKRPIREVPVTKLIDLEEDSYlekeksllqmvpldegtSERPLQVPKEIWLLVDHLFK 514
Cdd:cd04380     1 FITVTGVYLPSCFGSSLETLIRLPDPGIRNLIDQLELGDNPDY-----------------SEVPLSIPKEIWRLVDYLYT 63

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907204050 515 YACHQEDLFQTPGMQEE----LQQIIDCLDTSIPETIPGNNHSVAEALLIFLEALPEPVICYELYQRCLDS-AHDPRICK 589
Cdd:cd04380    64 RGLAQEGLFEEPGLPSEpgelLAEIRDALDTGSPFNSPGSAESVAEALLLFLESLPDPIIPYSLYERLLEAvANNEEDKR 143

                         170       180       190       200       210       220       230
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 1907204050 590 QVIS-QLPRCHRNVFRYLMAFLRELLKFSDYNNINTNMIATLFSSLLLRPPPNLMTRQTPNDRQHAIQFLLVFLL 663
Cdd:cd04380   144 QVIRiSLPPVHRNVFVYLCSFLRELLSESADRGLDENTLATIFGRVLLRDPPRAGGKERRAERDRKRAFIEQFLL 218
COG5411 COG5411
Phosphatidylinositol 5-phosphate phosphatase [Signal transduction mechanisms];
10-307 1.19e-61

Phosphatidylinositol 5-phosphate phosphatase [Signal transduction mechanisms];


Pssm-ID: 227698 [Multi-domain]  Cd Length: 460  Bit Score: 212.72  E-value: 1.19e-61
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907204050  10 FVGTWNVNGQSPDSSLEPWL---DCDPNPPDIYCIGFQELDLSTEAFF--YFESVKEQEWSLAVERGLPSKAKYRKVQLV 84
Cdd:COG5411    33 FVSTFNPPGKPPKASTKRWLfpeIEATELADLYVVGLQEVVELTPGSIlsADPYDRLRIWESKVLDCLNGAQSDEKYSLL 112

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907204050  85 R---LVGMMLLIFARKDQCQYIRDVATETTGTGIMGKMGNKGGVAVRFVFHNTTFCIVNSHLAAHVEEFERRNQDYKDIC 161
Cdd:COG5411   113 RspqLGGILLRVFSLATNLPVVKPVSGTVKKTGFGGSSSNKGAVAIRFNYERTSFCFVNSHLAAGVNNIEERIFDYRSIA 192

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907204050 162 ARMTFSvpnqtvPQVNIMKHDVVIWLGDLNYRLCM-PDASEVKSLINKNELHKLLKFDQLNIQRTQKKAFADFNEGEINF 240
Cdd:COG5411   193 SNICFS------RGLRIYDHDTIFWLGDLNYRVTStNEEVRPEIASDDGRLDKLFEYDQLLWEMEVGNVFPGFKEPVITF 266

                         250       260       270       280       290       300
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 1907204050 241 VPTYKYDSKTDRWDSSGKCRVPAWCDRILWRGINVNQLHYRSHMELKTSDHKPVSALFHIGVKVVDE 307
Cdd:COG5411   267 PPTYKFDYGTDEYDTSDKGRIPSWTDRILYKSEQLTPHSYSSIPHLMISDHRPVYATFRAKIKVVDP 333
PLN03191 PLN03191
Type I inositol-1,4,5-trisphosphate 5-phosphatase 2; Provisional
 74-312 1.72e-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: 1.72e-50
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907204050  74 SKAKYRKVQLVRLVGMMLLIFARKDQCQYIRDVATETTGTGIMGKMGNKGGVAVRFVFHNTTFCIVNSHLAA-HVEEFE- 151
Cdd:PLN03191  360 VKQKYVRIVSKQMVGIYVSVWVRKRLRRHINNLKVSPVGVGLMGYMGNKGSVSISMSLFQSRLCFVCSHLTSgHKDGAEq 439

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907204050 152 RRNQDYKDICARMTF-SVPNQTVPQvNIMKHDVVIWLGDLNYRLCMPDaSEVKSLINKNELHKLLKFDQLNIQRTQKKAF 230
Cdd:PLN03191  440 RRNADVYEIIRRTRFsSVLDTDQPQ-TIPSHDQIFWFGDLNYRLNMLD-TEVRKLVAQKRWDELINSDQLIKELRSGHVF 517

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907204050 231 ADFNEGEINFVPTYKYDSKTDRW-----DSSGKCRVPAWCDRILWRGINVNQLHYRsHMELKTSDHKPVSALFHIGVKVV 305
Cdd:PLN03191  518 DGWKEGPIKFPPTYKYEINSDRYvgenpKEGEKKRSPAWCDRILWLGKGIKQLCYK-RSEIRLSDHRPVSSMFLVEVEVF 596


                  ....*..
gi 1907204050 306 DERRYRK 312
Cdd:PLN03191  597 DHRKLQR 603
RhoGAP smart00324
GTPase-activator protein for Rho-like GTPases; GTPase activator proteins towards Rho/Rac ...
 500-661 1.27e-38

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: 140.48  E-value: 1.27e-38
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907204050  500 QVPKEIWLLVDHLFKYACHQEDLFQTPGMQEELQQIIDCLDTSIPETIP---GNNHSVAEALLIFLEALPEPVICYELYQ 576
Cdd:smart00324   2 PIPIIVEKCIEYLEKRGLDTEGIYRVSGSKSRVKELRDAFDSGPDPDLDlseYDVHDVAGLLKLFLRELPEPLITYELYE 81

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907204050  577 RCLDSAHDP------RICKQVISQLPRCHRNVFRYLMAFLRELLKFSDYNNINTNMIATLFSSLLLRPPPNLMTR-QTPN 649
Cdd:smart00324  82 EFIEAAKLEdeterlRALRELLSLLPPANRATLRYLLAHLNRVAEHSEENKMTARNLAIVFGPTLLRPPDGEVASlKDIR 161

                          170
                   ....*....|..
gi 1907204050  650 DRQHAIQFLLVF 661
Cdd:smart00324 162 HQNTVIEFLIEN 173
RhoGAP pfam00620
RhoGAP domain; GTPase activator proteins towards Rho/Rac/Cdc42-like small GTPases.
 502-640 3.05e-35

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


Pssm-ID: 459875  Cd Length: 148  Bit Score: 130.36  E-value: 3.05e-35
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907204050 502 PKEIWLLVDHLFKYACHQEDLFQTPGMQEELQQIIDCLD-TSIPETIPGNN--HSVAEALLIFLEALPEPVICYELYQRC 578
Cdd:pfam00620   1 PLIVRKCVEYLEKRGLDTEGIFRVSGSASRIKELREAFDrGPDVDLDLEEEdvHVVASLLKLFLRELPEPLLTFELYEEF 80

                          90       100       110       120       130       140
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 1907204050 579 LDSAHDP------RICKQVISQLPRCHRNVFRYLMAFLRELLKFSDYNNINTNMIATLFSSLLLRPPP 640
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 ...
 9-300 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: 583.12  E-value: 0e+00
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907204050   9 FFVGTWNVNGQSPDSSLEPWLDCDPNPPDIYCIGFQELDLSTEAFFYFESVKEQEWSLAVERGLPSKAKYRKVQLVRLVG 88
Cdd:cd09093     3 IFVGTWNVNGQSPDESLRPWLSCDEEPPDIYAIGFQELDLSAEAFLFNDSSREQEWVKAVERGLHPDAKYKKVKLIRLVG 82

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907204050  89 MMLLIFARKDQCQYIRDVATETTGTGIMGKMGNKGGVAVRFVFHNTTFCIVNSHLAAHVEEFERRNQDYKDICARMTFSV 168
Cdd:cd09093    83 MMLLVFVKKEHRQHIKEVAAETVGTGIMGKMGNKGGVAVRFQFHNTTFCFVNSHLAAHMEEVERRNQDYKDICARMKFED 162

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907204050 169 PNQtvPQVNIMKHDVVIWLGDLNYRLCMPDASEVKSLINKNELHKLLKFDQLNIQRTQKKAFADFNEGEINFVPTYKYDS 248
Cdd:cd09093   163 PDG--PPLSISDHDVVFWLGDLNYRIQELPTEEVKELIEKNDLEELLKYDQLNIQRRAGKVFEGFTEGEINFIPTYKYDP 240

                         250       260       270       280       290
                  ....*....|....*....|....*....|....*....|....*....|..
gi 1907204050 249 KTDRWDSSGKCRVPAWCDRILWRGINVNQLHYRSHMELKTSDHKPVSALFHI 300
Cdd:cd09093   241 GTDNWDSSEKCRAPAWCDRILWRGTNIVQLSYRSHMELKTSDHKPVSALFDI 292
IPPc smart00128
Inositol polyphosphate phosphatase, catalytic domain homologues; Mg(2+)-dependent/Li(+) ...
 9-303 3.63e-126

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


Pssm-ID: 214525 [Multi-domain]  Cd Length: 306  Bit Score: 375.54  E-value: 3.63e-126
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907204050    9 FFVGTWNVNGQS-PDSSLEPWLDC-----DPNPPDIYCIGFQELDLSTE-AFFYFESVKEQEWSLAVERGLPSKAKYRKV 81
Cdd:smart00128   5 VLIGTWNVGGLEsPKVDVTSWLFQkievkQSEKPDIYVIGLQEVVGLAPgVILETIAGKERLWSDLLESSLNGDGQYNVL 84

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907204050   82 QLVRLVGMMLLIFARKDQCQYIRDVATETTGTGIMGKMGNKGGVAVRFVFHNTTFCIVNSHLAAHVEEFERRNQDYKDIC 161
Cdd:smart00128  85 AKVYLVGILVLVFVKANHLVYIKDVETFTVKTGMGGLWGNKGAVAVRFKLSDTSFCFVNSHLAAGASNVEQRNQDYKTIL 164

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907204050  162 ARMTFSVPnqtvPQVNIMKHDVVIWLGDLNYRLCMPDASEVKSLINKNELHKLLKFDQLNIQRTQKKAFADFNEGEINFV 241
Cdd:smart00128 165 RALSFPER----ALLSQFDHDVVFWFGDLNFRLDSPSYEEVRRKISKKEFDDLLEKDQLNRQREAGKVFKGFQEGPITFP 240

                          250       260       270       280       290       300
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 1907204050  242 PTYKYDS-KTDRWDSSGKCRVPAWCDRILWR--GINVNQL-HYRSHMELKTSDHKPVSALFHIGVK 303
Cdd:smart00128 241 PTYKYDSvGTETYDTSEKKRVPAWCDRILYRsnGPELIQLsEYHSGMEITTSDHKPVFATFRLKVT 306
INPP5c cd09074
Catalytic domain of inositol polyphosphate 5-phosphatases; Inositol polyphosphate ...
 9-300 6.60e-120

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: 359.34  E-value: 6.60e-120
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907204050   9 FFVGTWNVNGQ-SPDSSLEPWLDCDPN-PPDIYCIGFQELDLSTEAFFYFE-SVKEQEWSLAVERGLPSKAKYRKVQLVR 85
Cdd:cd09074     3 IFVVTWNVGGGiSPPENLENWLSPKGTeAPDIYAVGVQEVDMSVQGFVGNDdSAKAREWVDNIQEALNEKENYVLLGSAQ 82

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907204050  86 LVGMMLLIFARKDQCQYIRD--VATETTGTGIMGKMGNKGGVAVRFVFHNTTFCIVNSHLAAHVEEFERRNQDYKDICAR 163
Cdd:cd09074    83 LVGIFLFVFVKKEHLPQIKDleVEGVTVGTGGGGKLGNKGGVAIRFQINDTSFCFVNSHLAAGQEEVERRNQDYRDILSK 162

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907204050 164 MTFSVPNQtvPQVNIMKHDVVIWLGDLNYRLCMpDASEVKSLINKNELHKLLKFDQLNIQRTQKKAFADFNEGEINFVPT 243
Cdd:cd09074   163 LKFYRGDP--AIDSIFDHDVVFWFGDLNYRIDS-TDDEVRKLISQGDLDDLLEKDQLKKQKEKGKVFDGFQELPITFPPT 239

                         250       260       270       280       290       300
                  ....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907204050 244 YKYDSKTDRWDSSGKCRVPAWCDRILWR---GINVNQLHYRSHMELKTSDHKPVSALFHI 300
Cdd:cd09074   240 YKFDPGTDEYDTSDKKRIPAWCDRILYKskaGSEIQPLSYTSVPLYKTSDHKPVRATFRV 299
INPP5c_ScInp51p-like cd09090
Catalytic inositol polyphosphate 5-phosphatase (INPP5c) domain of Saccharomyces cerevisiae ...
 10-298 4.73e-95

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: 295.02  E-value: 4.73e-95
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907204050  10 FVGTWNVNGQSPDSSLEPWL--DCDPNPPDIYCIGFQEL-DLSTEAFFYFESVKEQEWSLAVERGL--PSKAKYRKVQLV 84
Cdd:cd09090     4 FVGTFNVNGKSYKDDLSSWLfpEENDELPDIVVIGLQEVvELTAGQILNSDPSKSSFWEKKIKTTLngRGGEKYVLLRSE 83

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907204050  85 RLVGMMLLIFARKDQCQYIRDVATETTGTGIMGKMGNKGGVAVRFVFHNTTFCIVNSHLAAHVEEFERRNQDYKDICARM 164
Cdd:cd09090    84 QLVGTALLFFVKESQLPKVKNVEGSTKKTGLGGMSGNKGAVAIRFDYGDTSFCFVTSHLAAGLTNYEERNNDYKTIARGL 163

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907204050 165 TFSvPNQTVPQvnimkHDVVIWLGDLNYRLCMPDaSEVKSLINKNELHKLLKFDQLNIQRTQKKAFADFNEGEINFVPTY 244
Cdd:cd09090   164 RFS-RGRTIKD-----HDHVIWLGDFNYRISLTN-EDVRRFILNGKLDKLLEYDQLNQQMNAGEVFPGFSEGPITFPPTY 236

                         250       260       270       280       290
                  ....*....|....*....|....*....|....*....|....*....|....
gi 1907204050 245 KYDSKTDRWDSSGKCRVPAWCDRILWRGINVNQLHYRShMELKTSDHKPVSALF 298
Cdd:cd09090   237 KYDKGTDNYDTSEKQRIPAWTDRILYRGENLRQLSYNS-APLRFSDHRPVYATF 289
INPP5c_Synj cd09089
Catalytic inositol polyphosphate 5-phosphatase (INPP5c) domain of synaptojanins; This ...
 10-300 3.99e-91

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: 286.21  E-value: 3.99e-91
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907204050  10 FVGTWNVNGQS-------PDSSLEPWL--------------DCDPNPPDIYCIGFQEL-DLSTEAFFYFESVKEQEWSLA 67
Cdd:cd09089     4 FVGTWNVNGGKhfrsiafKHQSMTDWLldnpklagqcsndsEEDEKPVDIFAIGFEEMvDLNASNIVSASTTNQKEWGEE 83

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907204050  68 VERGLPSKAKYRKVQLVRLVGMMLLIFARKDQCQYIRDVATETTGTGIMGKMGNKGGVAVRFVFHNTTFCIVNSHLAAHV 147
Cdd:cd09089    84 LQKTISRDHKYVLLTSEQLVGVCLFVFVRPQHAPFIRDVAVDTVKTGLGGAAGNKGAVAIRFLLHSTSLCFVCSHFAAGQ 163

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907204050 148 EEFERRNQDYKDICARMTFsvPNQTvpqvNIMKHDVVIWLGDLNYRLCMPDaSEVKSLINKNELHKLLKFDQLNIQRTQK 227
Cdd:cd09089   164 SQVKERNEDFAEIARKLSF--PMGR----TLDSHDYVFWCGDFNYRIDLPN-DEVKELVRNGDWLKLLEFDQLTKQKAAG 236

                         250       260       270       280       290       300       310       320
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907204050 228 KAFADFNEGEINFVPTYKYDSKTDRWDSSGKCRVPAWCDRILWRGINV--------------------NQLHYRsHMELK 287
Cdd:cd09089   237 NVFKGFLEGEINFAPTYKYDLFSDDYDTSEKCRTPAWTDRVLWRRRKWpsdkteeslvetndptwnpgTLLYYG-RAELK 315

                         330
                  ....*....|...
gi 1907204050 288 TSDHKPVSALFHI 300
Cdd:cd09089   316 TSDHRPVVAIIDI 328
INPP5c_INPP5J-like cd09094
Catalytic inositol polyphosphate 5-phosphatase (INPP5c) domain of inositol polyphosphate ...
 10-300 6.91e-90

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: 281.95  E-value: 6.91e-90
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907204050  10 FVGTWNVNGQSPDSSLEPWLDCDPNP--PDIYCIGFQELDlSTEAFFYFESVKEQEWSLAVERGLpSKAKYRKVQLVRLV 87
Cdd:cd09094     4 YVVTWNVATAPPPIDVRSLLGLQSPEvaPDIYIIGLQEVN-SKPVQFVSDLIFDDPWSDLFMDIL-SPKGYVKVSSIRLQ 81

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907204050  88 GMMLLIFARKDQCQYIRDVATETTGTGIMGKMGNKGGVAVRFVFHNTTFCIVNSHLAAHVEEFERRNQDYKDICARMTFS 167
Cdd:cd09094    82 GLLLLVFVKIQHLPFIRDVQTNYTRTGLGGYWGNKGAVTVRFSLYGHMICFLNCHLPAHMEKWEQRIDDFETILSTQVFN 161

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907204050 168 VPNQTvpqvNIMKHDVVIWLGDLNYRLCMPDASEVKSLINKNELHKLLKFDQLNIQRTQKKAFADFNEGEINFVPTYKYD 247
Cdd:cd09094   162 ECNTP----SILDHDYVFWFGDLNFRIEDVSIEFVRELVNSKKYHLLLEKDQLNMAKRKEEAFQGFQEGPLNFAPTYKFD 237

                         250       260       270       280       290       300
                  ....*....|....*....|....*....|....*....|....*....|....*....|...
gi 1907204050 248 SKTDRWDSSGKCRVPAWCDRILWR----------GINVNQLHYRSHMELKTSDHKPVSALFHI 300
Cdd:cd09094   238 LGTDEYDTSGKKRKPAWTDRILWKvnpdasteekFLSITQTSYKSHMEYGISDHKPVTAQFRL 300
RhoGAP_OCRL1 cd04380
RhoGAP_OCRL1: RhoGAP (GTPase-activator protein [GAP] for Rho-like small GTPases) domain ...
 435-663 4.99e-86

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: 268.83  E-value: 4.99e-86
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907204050 435 FLTIGGNYLPSCFGTSLEALCRMKRPIREVPVTKLIDLEEDSYlekeksllqmvpldegtSERPLQVPKEIWLLVDHLFK 514
Cdd:cd04380     1 FITVTGVYLPSCFGSSLETLIRLPDPGIRNLIDQLELGDNPDY-----------------SEVPLSIPKEIWRLVDYLYT 63

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907204050 515 YACHQEDLFQTPGMQEE----LQQIIDCLDTSIPETIPGNNHSVAEALLIFLEALPEPVICYELYQRCLDS-AHDPRICK 589
Cdd:cd04380    64 RGLAQEGLFEEPGLPSEpgelLAEIRDALDTGSPFNSPGSAESVAEALLLFLESLPDPIIPYSLYERLLEAvANNEEDKR 143

                         170       180       190       200       210       220       230
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 1907204050 590 QVIS-QLPRCHRNVFRYLMAFLRELLKFSDYNNINTNMIATLFSSLLLRPPPNLMTRQTPNDRQHAIQFLLVFLL 663
Cdd:cd04380   144 QVIRiSLPPVHRNVFVYLCSFLRELLSESADRGLDENTLATIFGRVLLRDPPRAGGKERRAERDRKRAFIEQFLL 218
INPP5c_Synj2 cd09099
Catalytic inositol polyphosphate 5-phosphatase (INPP5c) domain of synaptojanin 2; This ...
 11-300 5.25e-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: 246.86  E-value: 5.25e-76
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907204050  11 VGTWNVNGQSP-------DSSLEPWL-------------DCDPNPPDIYCIGFQEL-DLSTEAFFYFESVKEQEWSLAVE 69
Cdd:cd09099     5 MGTWNVNGGKQfrsnilgTSELTDWLldspklsgtpdfqDDESNPPDIFAVGFEEMvELSAGNIVNASTTNRKMWGEQLQ 84

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907204050  70 RGLPSKAKYRKVQLVRLVGMMLLIFARKDQCQYIRDVATETTGTGIMGKMGNKGGVAVRFVFHNTTFCIVNSHLAAHVEE 149
Cdd:cd09099    85 KAISRSHRYILLTSAQLVGVCLFIFVRPYHVPFIRDVAIDTVKTGMGGKAGNKGAVAIRFQFYSTSFCFICSHLTAGQNQ 164

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907204050 150 FERRNQDYKDICARMTFSVPNqtvpqvNIMKHDVVIWLGDLNYRLCMPdASEVKSLINKNELHKLLKFDQLNIQRTQKKA 229
Cdd:cd09099   165 VKERNEDYKEITQKLSFPMGR------NVFSHDYVFWCGDFNYRIDLT-YEEVFYFIKRQDWKKLLEFDQLQLQKSSGKI 237

                         250       260       270       280       290       300       310       320
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907204050 230 FADFNEGEINFVPTYKYDSKTDRWDSSGKCRVPAWCDRILW-----------RGINV-----------------NQLHYR 281
Cdd:cd09099   238 FKDFHEGTINFGPTYKYDVGSEAYDTSDKCRTPAWTDRVLWwrkkwpfektaGEINLldsdldfdtkirhtwtpGALMYY 317

                         330
                  ....*....|....*....
gi 1907204050 282 SHMELKTSDHKPVSALFHI 300
Cdd:cd09099   318 GRAELQASDHRPVLAIVEV 336
INPP5c_Synj1 cd09098
Catalytic inositol polyphosphate 5-phosphatase (INPP5c) domain of synaptojanin 1; This ...
 11-300 5.38e-69

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: 228.39  E-value: 5.38e-69
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907204050  11 VGTWNVNGQSP-------DSSLEPWL-------------DCDPNPPDIYCIGFQEL-DLSTEAFFYFESVKEQEWSLAVE 69
Cdd:cd09098     5 VGTWNVNGGKQfrsiafkNQTLTDWLldapkkagipefqDVRSKPVDIFAIGFEEMvELNAGNIVSASTTNQKLWAAELQ 84

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907204050  70 RGLPSKAKYRKVQLVRLVGMMLLIFARKDQCQYIRDVATETTGTGIMGKMGNKGGVAVRFVFHNTTFCIVNSHLAAHVEE 149
Cdd:cd09098    85 KTISRDQKYVLLASEQLVGVCLFVFIRPQHAPFIRDVAVDTVKTGMGGATGNKGAVAIRMLFHTTSLCFVCSHFAAGQSQ 164

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907204050 150 FERRNQDYKDICARMTFSVPNQtvpqvnIMKHDVVIWLGDLNYRLCMPDaSEVKSLINKNELHKLLKFDQLNIQRTQKKA 229
Cdd:cd09098   165 VKERNEDFIEIARKLSFPMGRM------LFSHDYVFWCGDFNYRIDIPN-EEVKELIRQQNWDSLIAGDQLINQKNAGQV 237

                         250       260       270       280       290       300       310       320
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907204050 230 FADFNEGEINFVPTYKYDSKTDRWDSSGKCRVPAWCDRILWR------------------GINVNQ-----------LHY 280
Cdd:cd09098   238 FRGFLEGKLDFAPTYKYDLFSDDYDTSEKCRTPAWTDRVLWRrrkwpfdrsaedldllnaSFPDNSkeqytwspgtlLHY 317

                         330       340
                  ....*....|....*....|
gi 1907204050 281 rSHMELKTSDHKPVSALFHI 300
Cdd:cd09098   318 -GRAELKTSDHRPVVALIDI 336
COG5411 COG5411
Phosphatidylinositol 5-phosphate phosphatase [Signal transduction mechanisms];
10-307 1.19e-61

Phosphatidylinositol 5-phosphate phosphatase [Signal transduction mechanisms];


Pssm-ID: 227698 [Multi-domain]  Cd Length: 460  Bit Score: 212.72  E-value: 1.19e-61
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907204050  10 FVGTWNVNGQSPDSSLEPWL---DCDPNPPDIYCIGFQELDLSTEAFF--YFESVKEQEWSLAVERGLPSKAKYRKVQLV 84
Cdd:COG5411    33 FVSTFNPPGKPPKASTKRWLfpeIEATELADLYVVGLQEVVELTPGSIlsADPYDRLRIWESKVLDCLNGAQSDEKYSLL 112

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907204050  85 R---LVGMMLLIFARKDQCQYIRDVATETTGTGIMGKMGNKGGVAVRFVFHNTTFCIVNSHLAAHVEEFERRNQDYKDIC 161
Cdd:COG5411   113 RspqLGGILLRVFSLATNLPVVKPVSGTVKKTGFGGSSSNKGAVAIRFNYERTSFCFVNSHLAAGVNNIEERIFDYRSIA 192

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907204050 162 ARMTFSvpnqtvPQVNIMKHDVVIWLGDLNYRLCM-PDASEVKSLINKNELHKLLKFDQLNIQRTQKKAFADFNEGEINF 240
Cdd:COG5411   193 SNICFS------RGLRIYDHDTIFWLGDLNYRVTStNEEVRPEIASDDGRLDKLFEYDQLLWEMEVGNVFPGFKEPVITF 266

                         250       260       270       280       290       300
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 1907204050 241 VPTYKYDSKTDRWDSSGKCRVPAWCDRILWRGINVNQLHYRSHMELKTSDHKPVSALFHIGVKVVDE 307
Cdd:COG5411   267 PPTYKFDYGTDEYDTSDKGRIPSWTDRILYKSEQLTPHSYSSIPHLMISDHRPVYATFRAKIKVVDP 333
INPP5c_SHIP cd09091
Catalytic inositol polyphosphate 5-phosphatase (INPP5c) domain of SH2 domain containing ...
 10-300 3.62e-53

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: 185.15  E-value: 3.62e-53
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907204050  10 FVGTWNVNGQSPDSSLEPWLDC-----------DPNPPDIYCIGFQEldlsteaffyfESVKEQEWSLAVERGLP--SKA 76
Cdd:cd09091     4 FIGTWNMGSAPPPKNITSWFTSkgqgktrddvaDYIPHDIYVIGTQE-----------DPLGEKEWLDLLRHSLKelTSL 72

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907204050  77 KYRKVQLVRLVGMMLLIFARKDQCQYIRDVATETTGTGIMGKMGNKGGVAVRFVFHNTTFCIVNSHLAAHVEEFERRNQD 156
Cdd:cd09091    73 DYKPIAMQTLWNIRIVVLAKPEHENRISHVCTSSVKTGIANTLGNKGAVGVSFMFNGTSFGFVNSHLTSGSEKKLRRNQN 152

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907204050 157 YKDICARMtfSVPNQTVPQVNI-MKHDVVIWLGDLNYRLCMPDaSEVKSLINKNELHK---LLKFDQLNIQRTQKKAFAD 232
Cdd:cd09091   153 YLNILRFL--SLGDKKLSAFNItHRFTHLFWLGDLNYRLDLPI-QEAENIIQKIEQQQfepLLRHDQLNLEREEHKVFLR 229

                         250       260       270       280       290       300       310       320
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907204050 233 FNEGEINFVPTYKYDSKT-DRW-----DSSG-KCRVPAWCDRILWRgiNVNQLH-----YRSHMELKTSDHKPVSALFHI 300
Cdd:cd09091   230 FSEEEITFPPTYRYERGSrDTYaytkqKATGvKYNLPSWCDRILWK--SYPETHiicqsYGCTDDIVTSDHSPVFGTFEV 307
INPP5c_SHIP1-INPP5D cd09100
Catalytic inositol polyphosphate 5-phosphatase (INPP5c) domain of SH2 domain containing ...
 10-300 3.41e-52

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: 182.49  E-value: 3.41e-52
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907204050  10 FVGTWNVNGQSPDSSLEPWLDC-----------DPNPPDIYCIGFQELDLSteaffyfesvkEQEWSLAVERGLP--SKA 76
Cdd:cd09100     4 FIGTWNMGNAPPPKKITSWFQCkgqgktrddtaDYIPHDIYVIGTQEDPLG-----------EKEWLDTLKHSLReiTSI 72

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907204050  77 KYRKVQLVRLVGMMLLIFARKDQCQYIRDVATETTGTGIMGKMGNKGGVAVRFVFHNTTFCIVNSHLAAHVEEFERRNQD 156
Cdd:cd09100    73 SFKVIAIQTLWNIRIVVLAKPEHENRISHICTDSVKTGIANTLGNKGAVGVSFMFNGTSFGFVNSHLTSGSEKKLRRNQN 152

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907204050 157 YKDICARMTFSvpNQTVPQVNIM-KHDVVIWLGDLNYRLCMP--DASEVKSLINKNELHKLLKFDQLNIQRTQKKAFADF 233
Cdd:cd09100   153 YFNILRFLVLG--DKKLSPFNIThRFTHLFWLGDLNYRVELPntEAENIIQKIKQQQYQELLPHDQLLIERKESKVFLQF 230

                         250       260       270       280       290       300       310
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 1907204050 234 NEGEINFVPTYKYDSKT-DRW-----DSSG-KCRVPAWCDRILWRG---INVNQLHYRSHMELKTSDHKPVSALFHI 300
Cdd:cd09100   231 EEEEITFAPTYRFERGTrERYaytkqKATGmKYNLPSWCDRVLWKSyplVHVVCQSYGCTDDITTSDHSPVFATFEV 307
INPP5c_SHIP2-INPPL1 cd09101
Catalytic inositol polyphosphate 5-phosphatase (INPP5c) domain of SH2 domain containing ...
 10-300 1.38e-51

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: 180.94  E-value: 1.38e-51
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907204050  10 FVGTWNVNGQSPDSSLEPWLDCD-----------PNPPDIYCIGFQEldlsteaffyfESVKEQEWSLAVERGLP--SKA 76
Cdd:cd09101     4 FIGTWNMGSVPPPKSLASWLTSRglgktldettvTIPHDIYVFGTQE-----------NSVGDREWVDFLRASLKelTDI 72

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907204050  77 KYRKVQLVRLVGMMLLIFARKDQCQYIRDVATETTGTGIMGKMGNKGGVAVRFVFHNTTFCIVNSHLAAHVEEFERRNQD 156
Cdd:cd09101    73 DYQPIALQCLWNIKMVVLVKPEHENRISHVHTSSVKTGIANTLGNKGAVGVSFMFNGTSFGFVNCHLTSGNEKTHRRNQN 152

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907204050 157 YKDICARMtfSVPNQTVPQVNI-MKHDVVIWLGDLNYRLCMpDASEVKSLINKNELHKLLKFDQLNIQRTQKKAFADFNE 235
Cdd:cd09101   153 YLDILRSL--SLGDKQLNAFDIsLRFTHLFWFGDLNYRLDM-DIQEILNYITRKEFDPLLAVDQLNLEREKNKVFLRFRE 229

                         250       260       270       280       290       300       310
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 1907204050 236 GEINFVPTYKYDSKT------DRWDSSG-KCRVPAWCDRILWRGINVNQL---HYRSHMELKTSDHKPVSALFHI 300
Cdd:cd09101   230 EEISFPPTYRYERGSrdtymwQKQKTTGmRTNVPSWCDRILWKSYPETHIvcnSYGCTDDIVTSDHSPVFGTFEV 304
PLN03191 PLN03191
Type I inositol-1,4,5-trisphosphate 5-phosphatase 2; Provisional
 74-312 1.72e-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: 1.72e-50
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907204050  74 SKAKYRKVQLVRLVGMMLLIFARKDQCQYIRDVATETTGTGIMGKMGNKGGVAVRFVFHNTTFCIVNSHLAA-HVEEFE- 151
Cdd:PLN03191  360 VKQKYVRIVSKQMVGIYVSVWVRKRLRRHINNLKVSPVGVGLMGYMGNKGSVSISMSLFQSRLCFVCSHLTSgHKDGAEq 439

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907204050 152 RRNQDYKDICARMTF-SVPNQTVPQvNIMKHDVVIWLGDLNYRLCMPDaSEVKSLINKNELHKLLKFDQLNIQRTQKKAF 230
Cdd:PLN03191  440 RRNADVYEIIRRTRFsSVLDTDQPQ-TIPSHDQIFWFGDLNYRLNMLD-TEVRKLVAQKRWDELINSDQLIKELRSGHVF 517

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907204050 231 ADFNEGEINFVPTYKYDSKTDRW-----DSSGKCRVPAWCDRILWRGINVNQLHYRsHMELKTSDHKPVSALFHIGVKVV 305
Cdd:PLN03191  518 DGWKEGPIKFPPTYKYEINSDRYvgenpKEGEKKRSPAWCDRILWLGKGIKQLCYK-RSEIRLSDHRPVSSMFLVEVEVF 596


                  ....*..
gi 1907204050 306 DERRYRK 312
Cdd:PLN03191  597 DHRKLQR 603
INPP5c_INPP5E-like cd09095
Catalytic inositol polyphosphate 5-phosphatase (INPP5c) domain of Inositol ...
 8-298 2.95e-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: 176.84  E-value: 2.95e-50
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907204050   8 GFFVGTWNVNGQS--PDSSLEPWLDCDPN-PPDIYCIGFQEldlsteaffyfESVKEQEWSLAVERGL-PSKAKYRKVQL 83
Cdd:cd09095     6 GIFVATWNMQGQKelPENLDDFLLPTSADfAQDIYVIGVQE-----------GCSDRREWEIRLQETLgPSHVLLHSASH 74

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907204050  84 VRLvgmMLLIFARKDQCQYIRDVATETTGTGIMGKMGNKGGVAVRFVFHNTTFCIVNSHLAAHVEEFERRNQDYKDICAR 163
Cdd:cd09095    75 GVL---HLAVFIRRDLIWFCSEVESATVTTRIVSQIKTKGALAISFTFFGTSFLFITSHFTSGDGKVKERVLDYNKIIQA 151

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907204050 164 MTF--SVPNQTVPQVN---IMKHDVVIWLGDLNYRLCMPdASEVKSLINKN---ELHKLLKFDQLNIQRTQKKAFADFNE 235
Cdd:cd09095   152 LNLprNVPTNPYKSESgdvTTRFDEVFWFGDFNFRLSGP-RHLVDALINQGqevDVSALLQHDQLTREMSKGSIFKGFQE 230

                         250       260       270       280       290       300
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 1907204050 236 GEINFVPTYKYDSKTDRWDSSGKCRVPAWCDRILWRGI---NVNQLHYRSHMELKTSDHKPVSALF 298
Cdd:cd09095   231 APIHFPPTYKFDIGSDVYDTSSKQRVPSYTDRILYRSRqkgDVCCLKYNSCPSIKTSDHRPVFALF 296
RhoGAP smart00324
GTPase-activator protein for Rho-like GTPases; GTPase activator proteins towards Rho/Rac ...
 500-661 1.27e-38

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: 140.48  E-value: 1.27e-38
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907204050  500 QVPKEIWLLVDHLFKYACHQEDLFQTPGMQEELQQIIDCLDTSIPETIP---GNNHSVAEALLIFLEALPEPVICYELYQ 576
Cdd:smart00324   2 PIPIIVEKCIEYLEKRGLDTEGIYRVSGSKSRVKELRDAFDSGPDPDLDlseYDVHDVAGLLKLFLRELPEPLITYELYE 81

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907204050  577 RCLDSAHDP------RICKQVISQLPRCHRNVFRYLMAFLRELLKFSDYNNINTNMIATLFSSLLLRPPPNLMTR-QTPN 649
Cdd:smart00324  82 EFIEAAKLEdeterlRALRELLSLLPPANRATLRYLLAHLNRVAEHSEENKMTARNLAIVFGPTLLRPPDGEVASlKDIR 161

                          170
                   ....*....|..
gi 1907204050  650 DRQHAIQFLLVF 661
Cdd:smart00324 162 HQNTVIEFLIEN 173
RhoGAP pfam00620
RhoGAP domain; GTPase activator proteins towards Rho/Rac/Cdc42-like small GTPases.
 502-640 3.05e-35

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


Pssm-ID: 459875  Cd Length: 148  Bit Score: 130.36  E-value: 3.05e-35
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907204050 502 PKEIWLLVDHLFKYACHQEDLFQTPGMQEELQQIIDCLD-TSIPETIPGNN--HSVAEALLIFLEALPEPVICYELYQRC 578
Cdd:pfam00620   1 PLIVRKCVEYLEKRGLDTEGIFRVSGSASRIKELREAFDrGPDVDLDLEEEdvHVVASLLKLFLRELPEPLLTFELYEEF 80

                          90       100       110       120       130       140
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 1907204050 579 LDSAHDP------RICKQVISQLPRCHRNVFRYLMAFLRELLKFSDYNNINTNMIATLFSSLLLRPPP 640
Cdd:pfam00620  81 IEAAKLPdeeerlEALRELLRKLPPANRDTLRYLLAHLNRVAQNSDVNKMNAHNLAIVFGPTLLRPPD 148
RhoGAP cd00159
RhoGAP: GTPase-activator protein (GAP) for Rho-like GTPases; GAPs towards Rho/Rac/Cdc42-like ...
 502-644 1.02e-25

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: 103.92  E-value: 1.02e-25
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907204050 502 PKEIWLLVDHLFKYACHQEDLFQTPGMQEELQQIIDCLD--TSIPETIPGNNHSVAEALLIFLEALPEPVICYELYQRCL 579
Cdd:cd00159     1 PLIIEKCIEYLEKNGLNTEGIFRVSGSASKIEELKKKFDrgEDIDDLEDYDVHDVASLLKLYLRELPEPLIPFELYDEFI 80

                          90       100       110       120       130       140       150
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|.
gi 1907204050 580 DSAHDPRI------CKQVISQLPRCHRNVFRYLMAFLRELLKFSDYNNINTNMIATLFSSLLLRPPPNLMT 644
Cdd:cd00159    81 ELAKIEDEeerieaLKELLKSLPPENRDLLKYLLKLLHKISQNSEVNKMTASNLAIVFAPTLLRPPDSDDE 151
RhoGAP_nadrin cd04386
RhoGAP_nadrin: RhoGAP (GTPase-activator protein [GAP] for Rho-like small GTPases) domain of ...
 488-639 1.50e-15

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: 75.57  E-value: 1.50e-15
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907204050 488 VPLDEGTSERPLQVPKEIWLLVDHLFKYACHQEDLFQTPGMQEELQQIIDCLD--TSIPETIPGNN--HSVAEALLIFLE 563
Cdd:cd04386     7 TPLEEHLKRTGREIALPIEACVMCLLETGMNEEGLFRVGGGASKLKRLKAALDagTFSLPLDEFYSdpHAVASALKSYLR 86

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907204050 564 ALPEPVICYELYQRCLDSAHDP------RICKQVISQLPRCHRNVFRYLMAFLRELLKFSDYNNINTNMIATLFSSLLLR 637
Cdd:cd04386    87 ELPDPLLTYNLYEDWVQAANKPdederlQAIWRILNKLPRENRDNLRYLIKFLSKLAQKSDENKMSPSNIAIVLAPNLLW 166


                  ..
gi 1907204050 638 PP 639
Cdd:cd04386   167 AK 168
RhoGAP_FAM13A1a cd04393
RhoGAP_FAM13A1a: RhoGAP (GTPase-activator protein [GAP] for Rho-like small GTPases) domain of ...
 488-631 1.35e-14

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: 72.49  E-value: 1.35e-14
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907204050 488 VPLDE----GTSERplQVPKEIWLLVDHLFKYACHQEDLFQTPGMQEELQQIIDCLDTSIPETI--PGNNHSVAEALLIF 561
Cdd:cd04393     5 VPLQElqqaGQPEN--GVPAVVRHIVEYLEQHGLEQEGLFRVNGNAETVEWLRQRLDSGEEVDLskEADVCSAASLLRLF 82

                          90       100       110       120       130       140       150
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 1907204050 562 LEALPEPVICYELYQRCLDSAHDPRI-------CKQVISQLPRCHRNVFRYLMAFLRELLKFSDYNNINTNMIATLF 631
Cdd:cd04393    83 LQELPEGLIPASLQIRLMQLYQDYNGedefgrkLRDLLQQLPPVNYSLLKFLCHFLSNVASQHHENRMTAENLAAVF 159
RhoGAP_chimaerin cd04372
RhoGAP_chimaerin: RhoGAP (GTPase-activator protein [GAP] for Rho-like small GTPases) domain of ...
 519-667 1.17e-12

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: 67.16  E-value: 1.17e-12
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907204050 519 QEDLFQTPGMQEELQQIIDCLD-----TSIPETIPGNNHSVAEALLIFLEALPEPVICYELYQRCLDSA----HDPRI-- 587
Cdd:cd04372    34 SEGLYRVSGFAEEIEDVKMAFDrdgekADISATVYPDINVITGALKLYFRDLPIPVITYDTYPKFIDAAkisnPDERLea 113

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907204050 588 CKQVISQLPRCHRNVFRYLMAFLRELLKFSDYNNINTNMIATLFSSLLLRpPPNLMTRQTPNDRQHAIqFLLVFLLGNEE 667
Cdd:cd04372   114 VHEALMLLPPAHYETLRYLMEHLKRVTLHEKDNKMNAENLGIVFGPTLMR-PPEDSALTTLNDMRYQI-LIVQLLITNED 191
RhoGAP_KIAA1688 cd04389
RhoGAP_KIAA1688: GTPase-activator protein (GAP) domain for Rho-like GTPases found in ...
 499-651 4.23e-12

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: 65.49  E-value: 4.23e-12
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907204050 499 LQVPKEIWLLVDHLFKYACHQ-EDLFQTPGMQEELQQIIDCLDT-SIPETIPGNNHSVAEALLIFLEALPEPVICYELYQ 576
Cdd:cd04389    19 LKLPWILTFLSEKVLALGGFQtEGIFRVPGDIDEVNELKLRVDQwDYPLSGLEDPHVPASLLKLWLRELEEPLIPDALYQ 98

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907204050 577 RCLDSAHDPRICKQVISQLPRCHRNVFRYLMAFLRELLKFS--DYNNINTNMIATLFSSLLLR---PPPNLMTRQTPNDR 651
Cdd:cd04389    99 QCISASEDPDKAVEIVQKLPIINRLVLCYLINFLQVFAQPEnvAHTKMDVSNLAMVFAPNILRctsDDPRVIFENTRKEM 178
RhoGAP-p50rhoGAP cd04404
RhoGAP-p50rhoGAP: RhoGAP (GTPase-activator protein [GAP] for Rho-like small GTPases) domain of ...
 549-661 5.85e-12

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: 65.05  E-value: 5.85e-12
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907204050 549 GNNHSVAEALLIFLEALPEPVICYELYQRC-----LDSAHDPRICKQVISQLPRCHRNVFRYLMAFLRELLKFSDYNNIN 623
Cdd:cd04404    73 EDVHLPAVILKTFLRELPEPLLTFDLYDDIvgflnVDKEERVERVKQLLQTLPEENYQVLKYLIKFLVQVSAHSDQNKMT 152

                          90       100       110
                  ....*....|....*....|....*....|....*...
gi 1907204050 624 TNMIATLFSSLLLRPPPNLMTRQTPNDRQHAIQFLLVF 661
Cdd:cd04404   153 NSNLAVVFGPNLLWAKDASMSLSAINPINTFTKFLLDH 190
RhoGAP_ARHGAP22_24_25 cd04390
RhoGAP_ARHGAP22_24_25: GTPase-activator protein (GAP) domain for Rho-like GTPases found in ...
 498-668 8.91e-12

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: 64.77  E-value: 8.91e-12
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907204050 498 PLQVPKEIWLLVDHLFKYACHQEDLFQTPGMQEELQQIIDCLDTSIPETIPGNN--HSVAEALLIFLEALPEPVICYELY 575
Cdd:cd04390    19 PRLVPILVEQCVDFIREHGLKEEGLFRLPGQANLVKQLQDAFDAGERPSFDSDTdvHTVASLLKLYLRELPEPVIPWAQY 98

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907204050 576 QRCLDSAH---------DPRICKQvISQLPRCHRNVFRYLMAFLRELLKFSDYNNINTNMIATLFSSLLLRPP---PNLM 643
Cdd:cd04390    99 EDFLSCAQllskdeekgLGELMKQ-VSILPKVNYNLLSYICRFLDEVQSNSSVNKMSVQNLATVFGPNILRPKvedPATI 177

                         170       180
                  ....*....|....*....|....*
gi 1907204050 644 TRQTPndrqhAIQFLLVFLLGNEED 668
Cdd:cd04390   178 MEGTP-----QIQQLMTVMISKHEP 197
RhoGAP_GMIP_PARG1 cd04378
RhoGAP_GMIP_PARG1: RhoGAP (GTPase-activator protein [GAP] for Rho-like small GTPases) domain ...
 552-640 7.03e-11

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: 62.05  E-value: 7.03e-11
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907204050 552 HSVAEALLIFLEALPEPVICYELY----------QRCLDSAHDPRIC----------KQVISQLPRCHRNVFRYLMAFLR 611
Cdd:cd04378    69 HDISSVLKLFLRQLPEPLILFRLYndfialakeiQRDTEEDKAPNTPievnriirklKDLLRQLPASNYNTLQHLIAHLY 148

                          90       100
                  ....*....|....*....|....*....
gi 1907204050 612 ELLKFSDYNNINTNMIATLFSSLLLRPPP 640
Cdd:cd04378   149 RVAEQFEENKMSPNNLGIVFGPTLIRPRP 177
RhoGAP_GMIP cd04408
RhoGAP_GMIP: RhoGAP (GTPase-activator protein [GAP] for Rho-like small GTPases) domain of GMIP ...
 552-640 5.05e-09

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: 56.75  E-value: 5.05e-09
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907204050 552 HSVAEALLIFLEALPEPVICYELYQ-----------------RCLDSAHDP-RICKQVISQLPRCHRNVFRYLMAFL-RE 612
Cdd:cd04408    69 HDITSVLKHFLKELPEPVLPFQLYDdfialakelqrdsekaaESPSIVENIiRSLKELLGRLPVSNYNTLRHLMAHLyRV 148

                          90       100
                  ....*....|....*....|....*...
gi 1907204050 613 LLKFSDyNNINTNMIATLFSSLLLRPPP 640
Cdd:cd04408   149 AERFED-NKMSPNNLGIVFGPTLLRPLV 175
RhoGAP_srGAP cd04383
RhoGAP_srGAP: RhoGAP (GTPase-activator protein [GAP] for Rho-like small GTPases) domain ...
 503-641 7.43e-09

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: 55.89  E-value: 7.43e-09
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907204050 503 KEIWLLVDHLFKYAC----HQEDLFQTPGMQEELQQIIDCLDT-SIPETIPGNNH---SVAEALLIFLEALPEPVICYEL 574
Cdd:cd04383    16 QAIPLVVESCIRFINlyglQHQGIFRVSGSQVEVNDIKNAFERgEDPLADDQNDHdinSVAGVLKLYFRGLENPLFPKER 95

                          90       100       110       120       130       140       150
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 1907204050 575 YQRCLDSAHD-------PRIcKQVISQLPRCHRNVFRYLMAFLRELLKFSDYNNINTNMIATLFSSLLLRPPPN 641
Cdd:cd04383    96 FEDLMSCVKLenptervHQI-REILSTLPRSVIIVMRYLFAFLNHLSQFSDENMMDPYNLAICFGPTLMPVPEG 168
RhoGAP_myosin_IX cd04377
RhoGAP_myosin_IX: RhoGAP (GTPase-activator protein [GAP] for Rho-like small GTPases) domain ...
 488-650 1.57e-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: 54.75  E-value: 1.57e-08
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907204050 488 VPLDEGTSERPlQVPKEIWLLVDHLFKYACHQEDLFQTPGMQEELQQIIDCLDTSiPETIPGNN---HSVAEALLIFLEA 564
Cdd:cd04377     3 VSLSSLTSEDR-SVPLVLEKLLEHIEMHGLYTEGIYRKSGSANKIKELRQGLDTD-PDSVNLEDypiHVITSVLKQWLRE 80

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907204050 565 LPEPVICYELYQRCLDSAHDPRICKQ------VISQLPRCHRNVFRYLMAFLRELLKFSDYNNINTNMIATLFSSLLLRP 638
Cdd:cd04377    81 LPEPLMTFELYENFLRAMELEEKQERvralysVLEQLPRANLNTLERLIFHLVRVALQEEVNRMSANALAIVFAPCILRC 160

                         170
                  ....*....|..
gi 1907204050 639 PPNLMTRQTPND 650
Cdd:cd04377   161 PDTADPLQSLQD 172
RhoGAP_myosin_IXB cd04407
RhoGAP_myosin_IXB: RhoGAP (GTPase-activator protein [GAP] for Rho-like small GTPases) domain ...
 488-641 3.48e-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: 53.84  E-value: 3.48e-08
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907204050 488 VPLDEGTSERPlQVPKEIWLLVDHLFKYACHQEDLFQTPGMQEELQQIIDCLDTSiPETIPGNN---HSVAEALLIFLEA 564
Cdd:cd04407     3 VRVGSLTSNKT-SVPIVLEKLLEHVEMHGLYTEGIYRKSGSANRMKELHQLLQAD-PENVKLENypiHAITGLLKQWLRE 80

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907204050 565 LPEPVICYELYQRCLDSAHDPRICKQ------VISQLPRCHRNVFRYLMAFLRELLKFSDYNNINTNMIATLFSSLLLRP 638
Cdd:cd04407    81 LPEPLMTFAQYNDFLRAVELPEKQEQlqaiyrVLEQLPTANHNTLERLIFHLVKVALEEDVNRMSPNALAIVFAPCLLRC 160


                  ...
gi 1907204050 639 PPN 641
Cdd:cd04407   161 PDS 163
RhoGAP_fRGD1 cd04398
RhoGAP_fRGD1: RhoGAP (GTPase-activator protein [GAP] for Rho-like small GTPases) domain of ...
 488-642 8.28e-08

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: 52.79  E-value: 8.28e-08
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907204050 488 VPLDEGTSERPLQVPKEIWLLVDHLFKYACHQEDLFQTPGMQEELQQIIDCLDT--SIPETIPGNN-----HSVAEALLI 560
Cdd:cd04398     3 VPLEDLILREGDNVPNIVYQCIQAIENFGLNLEGIYRLSGNVSRVNKLKELFDKdpLNVLLISPEDyesdiHSVASLLKL 82

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907204050 561 FLEALPEPVICYELYQRCLDSAH--DPRICK----QVISQLPRCHRNVFRYLMAFLRELLKFSDYNNINTNMIATLFSSL 634
Cdd:cd04398    83 FFRELPEPLLTKALSREFIEAAKieDESRRRdalhGLINDLPDANYATLRALMFHLARIKEHESVNRMSVNNLAIIWGPT 162


                  ....*....
gi 1907204050 635 LLR-PPPNL 642
Cdd:cd04398   163 LMNaAPDNA 171
RhoGAP_ARHGAP6 cd04376
RhoGAP_ARHGAP6: RhoGAP (GTPase-activator protein [GAP] for Rho-like small GTPases) domain of ...
 499-656 9.89e-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: 52.83  E-value: 9.89e-08
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907204050 499 LQVPKEIWLLVDHLFKYACHQEDLFQTPGMQEELQQI---IDC-LDTSIPETIpgNNHSVAEALLIFLEALPEPVICYEL 574
Cdd:cd04376     7 RQVPRLVESCCQHLEKHGLQTVGIFRVGSSKKRVRQLreeFDRgIDVVLDENH--SVHDVAALLKEFFRDMPDPLLPREL 84

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907204050 575 YQRCLDSAH---DPRI--CKQVISQLPRCHRNVFRYLMAFLRELLKFSDY-----------NNINTNMIATLFSslllrp 638
Cdd:cd04376    85 YTAFIGTALlepDEQLeaLQLLIYLLPPCNCDTLHRLLKFLHTVAEHAADsidedgqevsgNKMTSLNLATIFG------ 158

                         170
                  ....*....|....*...
gi 1907204050 639 pPNLMTRQTPNDRQHAIQ 656
Cdd:cd04376   159 -PNLLHKQKSGEREFVQA 175
INPP5A cd09092
Type I inositol polyphosphate 5-phosphatase I; Type I inositol polyphosphate 5-phosphatase I ...
 118-300 1.43e-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: 54.01  E-value: 1.43e-07
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907204050 118 KMGNKGGVAVRFVFHNTTFCIVNSHL---AAHVEEFERRNQDYKDICAR----MTFSVPNQTVPQVNImkhdvvIWLGDL 190
Cdd:cd09092   151 KWSRKGFMRTRWKINNCVFDLVNIHLfhdASNLAACESSPSVYSQNRHRalgyVLERLTDERFEKVPF------FVFGDF 224

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907204050 191 NYRLcmpDA-SEVKSLINKNELHKLLK----------FDQLNIQRT-----QKKAFADFN-------------------- 234
Cdd:cd09092   225 NFRL---DTkSVVETLCAKATMQTVRKadsnivvkleFREKDNDNKvvlqiEKKKFDYFNqdvfrdnngkallkfdkele 301

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907204050 235 -------EGEINFVPTYKYDSKTDRWDSSGKCRVPAWCDRIL--------WRGINVNQLHYRS-HMELKTSDHKPVSALF 298
Cdd:cd09092   302 vfkdvlyELDISFPPSYPYSEDPEQGTQYMNTRCPAWCDRILmshsarelKSENEEKSVTYDMiGPNVCMGDHKPVFLTF 381


                  ..
gi 1907204050 299 HI 300
Cdd:cd09092   382 RI 383
EEP cd08372
Exonuclease-Endonuclease-Phosphatase (EEP) domain superfamily; This large superfamily includes ...
 11-294 1.66e-07

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: 52.87  E-value: 1.66e-07
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907204050  11 VGTWNVNGQSPDSSLEPWL----DCDPnppDIYCIgfQELDLSTeAFFYFESVKEQEWSLAVERGLPSKAKYrkvqlvrl 86
Cdd:cd08372     1 VASYNVNGLNAATRASGIArwvrELDP---DIVCL--QEVKDSQ-YSAVALNQLLPEGYHQYQSGPSRKEGY-------- 66

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907204050  87 VGMMLLIFARKdqcqyiRDVATETTGTGIMGKMGNKGGVAVRFVFHNTTFCIVNSHLAAhveefERRNQDYKDICARMTF 166
Cdd:cd08372    67 EGVAILSKTPK------FKIVEKHQYKFGEGDSGERRAVVVKFDVHDKELCVVNAHLQA-----GGTRADVRDAQLKEVL 135

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907204050 167 SVpnqtVPQVNIMKHDVVIWLGDLNYRLcmpdaSEVkslinknELHKLLKFDQLNIQRTQKKAFADFnegeiNFVPTYKY 246
Cdd:cd08372   136 EF----LKRLRQPNSAPVVICGDFNVRP-----SEV-------DSENPSSMLRLFVALNLVDSFETL-----PHAYTFDT 194

                         250       260       270       280       290
                  ....*....|....*....|....*....|....*....|....*....|...
gi 1907204050 247 DSKtdrwdssgkcRVPAWCDRILWRG---INV--NQLHYRSHMELKTSDHKPV 294
Cdd:cd08372   195 YMH----------NVKSRLDYIFVSKsllPSVksSKILSDAARARIPSDHYPI 237
RhoGAP_CdGAP cd04384
RhoGAP_CdGAP: RhoGAP (GTPase-activator protein [GAP] for Rho-like small GTPases) domain of ...
 552-640 2.05e-07

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: 51.73  E-value: 2.05e-07
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907204050 552 HSVAEALLIFLEALPEPVICYELYQRCLDS-AHDP-----RICKQVISQLPRCHRNVFRYLMAFLRELLKFSDYNNINTN 625
Cdd:cd04384    73 HSVSSLCKLYFRELPNPLLTYQLYEKFSEAvSAASdeerlEKIHDVIQQLPPPHYRTLEFLMRHLSRLAKYCSITNMHAK 152

                          90
                  ....*....|....*
gi 1907204050 626 MIATLFSSLLLRPPP 640
Cdd:cd04384   153 NLAIVWAPNLLRSKQ 167
RhoGAP_ARAP cd04385
RhoGAP_ARAP: RhoGAP (GTPase-activator protein [GAP] for Rho-like small GTPases) domain present ...
 552-638 2.64e-07

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: 51.15  E-value: 2.64e-07
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907204050 552 HSVAEALLIFLEALPEPVICYELYQRCLDSAHDPRIC------KQVISQLPRCHRNVFRYLMAFLRELLKFSDYNNINTN 625
Cdd:cd04385    70 HDVADVLKRFLRDLPDPLLTSELHAEWIEAAELENKDeriaryKELIRRLPPINRATLKVLIGHLYRVQKHSDENQMSVH 149

                          90
                  ....*....|...
gi 1907204050 626 MIATLFSSLLLRP 638
Cdd:cd04385   150 NLALVFGPTLFQT 162
RhoGAP_fBEM3 cd04400
RhoGAP_fBEM3: RhoGAP (GTPase-activator [GAP] protein for Rho-like small GTPases) domain of ...
 552-643 2.96e-07

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: 51.21  E-value: 2.96e-07
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907204050 552 HSVAEALLIFLEALPEPVICYELY---QRCLDSAHDPR----ICKQVISQLPRCHRNVFRYLMAFLRELLKFSDYNNINT 624
Cdd:cd04400    79 HTVAGLLKLYLRELPTLILGGELHndfKRLVEENHDRSqralELKDLVSQLPQANYDLLYVLFSFLRKIIEHSDVNKMNL 158

                          90
                  ....*....|....*....
gi 1907204050 625 NMIATLFSSLLLRPPPNLM 643
Cdd:cd04400   159 RNVCIVFSPTLNIPAGIFV 177
RhoGAP_ARHGAP20 cd04402
RhoGAP_ARHGAP20: RhoGAP (GTPase-activator protein [GAP] for Rho-like small GTPases) domain of ...
 501-639 1.02e-06

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: 49.60  E-value: 1.02e-06
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907204050 501 VPKEIWLLVDHLFKYACHQEDLFQTPGMQEELQQIIDCLDTSI-PETIPGNNHSVAEALLIFLEALPEPVICYELYQRCL 579
Cdd:cd04402    15 LPKPILDMLSLLYQKGPSTEGIFRRSANAKACKELKEKLNSGVeVDLKAEPVLLLASVLKDFLRNIPGSLLSSDLYEEWM 94

                          90       100       110       120       130       140
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 1907204050 580 DSAHDPRI------CKQVISQLPRCHRNVFRYLMAFLRELLKFSDYNNINTNMIATLFSSLLLRPP 639
Cdd:cd04402    95 SALDQENEeekiaeLQRLLDKLPRPNVLLLKHLICVLHNISQNSETNKMDAFNLAVCIAPSLLWPP 160
RhoGAP_p190 cd04373
RhoGAP_p190: RhoGAP (GTPase-activator protein [GAP] for Rho-like small GTPases) domain of ...
 488-638 2.10e-06

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: 48.61  E-value: 2.10e-06
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907204050 488 VPL-DEGTSERPlqVPKEIWLLVDHLFKYACHQEDLFQTPGMQEELQQI-----------IDCLDTSIpetipgnnHSVA 555
Cdd:cd04373     3 VPLaNVVTSEKP--IPIFLEKCVEFIEATGLETEGIYRVSGNKTHLDSLqkqfdqdhnldLVSKDFTV--------NAVA 72

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907204050 556 EALLIFLEALPEPVICYELYQRCLDSAHDP-RIC-----KQVISQLPRCHRNVFRYLMAFLRELLKFSDYNNINTNMIAT 629
Cdd:cd04373    73 GALKSFFSELPDPLIPYSMHLELVEAAKINdREQrlhalKELLKKFPPENFDVFKYVITHLNKVSQNSKVNLMTSENLSI 152


                  ....*....
gi 1907204050 630 LFSSLLLRP 638
Cdd:cd04373   153 CFWPTLMRP 161
RhoGAP_Bcr cd04387
RhoGAP_Bcr: RhoGAP (GTPase-activator protein [GAP] for Rho-like small GTPases) domain of Bcr ...
 493-662 2.58e-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: 48.39  E-value: 2.58e-06
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907204050 493 GTSERPLQVPKEIWLLVDHLFKYACHQEDLFQTPGMQEELQQIIDCLDTSIPETI----PGNNHSVAEALLIFLEALPEP 568
Cdd:cd04387     8 VTKRERSKVPYIVRQCVEEVERRGMEEVGIYRISGVATDIQALKAAFDTNNKDVSvmlsEMDVNAIAGTLKLYFRELPEP 87

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907204050 569 VICYELYQRCLD--SAHDPRICK----QVISQLPRCHRNVFRYLMAFLRELLKFSDYNNINTNMIATLFSSLLLRP---- 638
Cdd:cd04387    88 LFTDELYPNFAEgiALSDPVAKEscmlNLLLSLPDPNLVTFLFLLHHLKRVAEREEVNKMSLHNLATVFGPTLLRPseke 167

                         170       180
                  ....*....|....*....|....*..
gi 1907204050 639 ---PPNLMTRQTPNDRQHAIQFLLVFL 662
Cdd:cd04387   168 skiPTNTMTDSWSLEVMSQVQVLLYFL 194
RhoGAP_myosin_IXA cd04406
RhoGAP_myosin_IXA: RhoGAP (GTPase-activator protein [GAP] for Rho-like small GTPases) domain ...
 501-650 3.00e-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: 48.07  E-value: 3.00e-06
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907204050 501 VPKEIWLLVDHLFKYACHQEDLFQTPGMQEELQQIIDCLDTSIPETIPG--NNHSVAEALLIFLEALPEPVICYELYQRC 578
Cdd:cd04406    15 VPLVVEKLINYIEMHGLYTEGIYRKSGSTNKIKELRQGLDTDANSVNLDdyNIHVIASVFKQWLRDLPNPLMTFELYEEF 94

                          90       100       110       120       130       140       150
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 1907204050 579 L------DSAHDPRICKQVISQLPRCHRNVFRYLMAFLRELLKFSDYNNINTNMIATLFSSLLLRPPPNLMTRQTPND 650
Cdd:cd04406    95 LramglqERRETVRGVYSVIDQLSRTHLNTLERLIFHLVRIALQEETNRMSANALAIVFAPCILRCPDTTDPLQSVQD 172
RhoGAP_p85 cd04388
RhoGAP_p85: RhoGAP (GTPase-activator protein [GAP] for Rho-like small GTPases) domain present ...
 524-640 7.51e-06

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: 47.18  E-value: 7.51e-06
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907204050 524 QTPGMQEELQQIIDClDTSIPETIPGNNHSVAEALLIFLEALPEPVICYELYQRCLDSAHDP---RICKQVISQLPRC-- 598
Cdd:cd04388    40 QSSSSLTELRQILDC-DAASVDLEQFDVAALADALKRYLLDLPNPVIPAPVYSEMISRAQEVqssDEYAQLLRKLIRSpn 118

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|....*.
gi 1907204050 599 ---HRNV-FRYLMAFLRELLKFSDYNNINTNMIATLFSSLLLRPPP 640
Cdd:cd04388   119 lphQYWLtLQYLLKHFFRLCQSSSKNLLSARALAEIFSPLLFRFQP 164
RhoGAP_fLRG1 cd04397
RhoGAP_fLRG1: RhoGAP (GTPase-activator protein [GAP] for Rho-like small GTPases) domain of ...
 531-667 8.89e-06

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: 47.36  E-value: 8.89e-06
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907204050 531 ELQQIIDCLDTSIPETIPGNNHSVAEALLIFLEALPEPVICYELYQRCLDSAH--DPRICKQVI----SQLPRCHRNVFR 604
Cdd:cd04397    60 ELTEEIDKNPTEVPDLSKENPVQLAALLKKFLRELPDPLLTFKLYRLWISSQKieDEEERKRVLhlvyCLLPKYHRDTME 139

                          90       100       110       120       130       140
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 1907204050 605 YLMAFLRELLKFSDYNN-----INTNMIATLFSSLLLRPPPNlmTRQTPNDRQHAIQFLLVFLLGNEE 667
Cdd:cd04397   140 VLFSFLKWVSSFSHIDEetgskMDIHNLATVITPNILYSKTD--NPNTGDEYFLAIEAVNYLIENNEE 205
RhoGAP_ARHGAP27_15_12_9 cd04403
RhoGAP_ARHGAP27_15_12_9: GTPase-activator protein (GAP) domain for Rho-like GTPases found in ...
 552-638 2.01e-05

RhoGAP_ARHGAP27_15_12_9: GTPase-activator protein (GAP) domain for Rho-like GTPases found in ARHGAP27 (also called CAMGAP1), ARHGAP15, 12 and 9-like proteins; This subgroup of ARHGAPs are multidomain proteins that contain RhoGAP, PH, SH3 and WW domains. Most members that are studied show GAP activity towards Rac1, some additionally show activity towards Cdc42. 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: 239868 [Multi-domain]  Cd Length: 187  Bit Score: 45.85  E-value: 2.01e-05
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907204050 552 HSVAEALLIFLEALPEPVICYELYQ--RCLDSAHDPRIC----KQVISQLPRCHRNVFRYLMAFLRELLKFSDYNNINTN 625
Cdd:cd04403    71 HVITGALKLFFRELPEPLFPYSLFNdfVAAIKLSDYEQRvsavKDLIKSLPKPNHDTLKMLFRHLCRVIEHGEKNRMTTQ 150

                          90
                  ....*....|...
gi 1907204050 626 MIATLFSSLLLRP 638
Cdd:cd04403   151 NLAIVFGPTLLRP 163
RhoGAP_PARG1 cd04409
RhoGAP_PARG1: RhoGAP (GTPase-activator protein [GAP] for Rho-like small GTPases) domain of ...
 552-640 3.17e-05

RhoGAP_PARG1: RhoGAP (GTPase-activator protein [GAP] for Rho-like small GTPases) domain of PARG1 (PTPL1-associated RhoGAP1). PARG1 was originally cloned as an interaction partner of PTPL1, an intracellular protein-tyrosine phosphatase. 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: 239874  Cd Length: 211  Bit Score: 45.57  E-value: 3.17e-05
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907204050 552 HSVAEALLIFLEALPEPVICYELYQRCLDSAHD------------------PRIC----------KQVISQLPRCHRNVF 603
Cdd:cd04409    69 HDISNVLKLYLRQLPEPLILFRLYNEFIGLAKEsqhvnetqeakknsdkkwPNMCtelnrillksKDLLRQLPAPNYNTL 148

                          90       100       110
                  ....*....|....*....|....*....|....*..
gi 1907204050 604 RYLMAFLRELLKFSDYNNINTNMIATLFSSLLLRPPP 640
Cdd:cd04409   149 QFLIVHLHRVSEQAEENKMSASNLGIIFGPTLIRPRP 185
RhoGAP-ARHGAP11A cd04394
RhoGAP-ARHGAP11A: RhoGAP (GTPase-activator protein [GAP] for Rho-like small GTPases) domain of ...
 508-636 5.72e-05

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: 44.77  E-value: 5.72e-05
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907204050 508 LVDHLfkyacHQEDLFQTPG---MQEELQQIID----CLDTSIPEtipgnnhSVAEALLIFLEALPEPVICYELYQRCLD 580
Cdd:cd04394    31 LLDHL-----STEGLFRKSGsvvRQKELKAKLEggeaCLSSALPC-------DVAGLLKQFFRELPEPLLPYDLHEALLK 98

                          90       100       110       120       130       140
                  ....*....|....*....|....*....|....*....|....*....|....*....|..
gi 1907204050 581 SAHDP----RICKQVISQ--LPRCHRNVFRYLMAFLRELLKFSDYNNINTNMIATLFSSLLL 636
Cdd:cd04394    99 AQELPtdeeRKSATLLLTclLPDEHVNTLRYFFSFLYDVAQRCSENKMDSSNLAVIFAPNLF 160
RhoGAP_ARHGAP21 cd04395
RhoGAP_ARHGAP21: RhoGAP (GTPase-activator protein [GAP] for Rho-like small GTPases) domain of ...
 528-644 6.11e-05

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: 44.31  E-value: 6.11e-05
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907204050 528 MQEELQQIIDCLDTSIPETipgNNHSVAEALL-IFLEALPEPVICYELYQRCLD----SAHDPRI--CKQVISQLPRCHR 600
Cdd:cd04395    52 LQEELNRGGFDIDLQDPRW---RDVNVVSSLLkSFFRKLPEPLFTNELYPDFIEanriEDPVERLkeLRRLIHSLPDHHY 128

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|....
gi 1907204050 601 NVFRYLMAFLRELLKFSDYNNINTNMIATLFSSLLLRPPPNLMT 644
Cdd:cd04395   129 ETLKHLIRHLKTVADNSEVNKMEPRNLAIVFGPTLVRTSDDNME 172
RhoGAP_ARHGAP18 cd04391
RhoGAP_ARHGAP18: RhoGAP (GTPase-activator protein [GAP] for Rho-like small GTPases) domain of ...
 488-641 4.05e-04

RhoGAP_ARHGAP18: RhoGAP (GTPase-activator protein [GAP] for Rho-like small GTPases) domain of ArhGAP18-like proteins. The function of ArhGAP18 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: 239856  Cd Length: 216  Bit Score: 42.33  E-value: 4.05e-04
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907204050 488 VPLD---EGTSERP--LQVPKEIWLLVDHLFKYACHQEDLFQTPGMQEELQQIIDCLDTSIPE-TIPGNNHSVAEA---L 558
Cdd:cd04391     4 VPLStllERDQKKVpgSKVPLIFQKLINKLEERGLETEGILRIPGSAQRVKFLCQELEAKFYEgTFLWDQVKQHDAaslL 83

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907204050 559 LIFLEALPEPVICYELYQRCLDSAHDPRICKQV------ISQLPRCHRNVFRYLMAFLRELLKFSDYNNINTNMIAT--- 629
Cdd:cd04391    84 KLFIRELPQPLLTVEYLPAFYSVQGLPSKKDQLqalnllVLLLPEANRDTLKALLEFLQKVVDHEEKNKMNLWNVAMima 163

                         170
                  ....*....|....
gi 1907204050 630 --LFSSLLLRPPPN 641
Cdd:cd04391   164 pnLFPPRGKHSKDN 177
RhoGAP_SYD1 cd04379
RhoGAP_SYD1: RhoGAP (GTPase-activator protein [GAP] for Rho-like small GTPases) domain present ...
 544-638 1.26e-03

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: 40.53  E-value: 1.26e-03
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907204050 544 PETIPGNNhSVAEALLIFLEALPEPVICYELYQRCLDSA-----HDP----RICKQVISQLPRCHRNVFRYLMAFLRELL 614
Cdd:cd04379    67 EELYPDIN-VITGVLKDYLRELPEPLITPQLYEMVLEALavalpNDVqtntHLTLSIIDCLPLSAKATLLLLLDHLSLVL 145

                          90       100
                  ....*....|....*....|....
gi 1907204050 615 KFSDYNNINTNMIATLFSSLLLRP 638
Cdd:cd04379   146 SNSERNKMTPQNLAVCFGPVLMFC 169
RhoGap_RalBP1 cd04381
RhoGap_RalBP1: RhoGAP (GTPase-activator protein [GAP] for Rho-like small GTPases) domain ...
 488-632 3.51e-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: 3.51e-03
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907204050 488 VPLDEGTsERP-----LQVPKEIWLLVDHLFKYACHQEDLFQTPGMQEELQQIIDCLD----TSIPETIPgnnHSVAEAL 558
Cdd:cd04381     3 ASLSLAV-ERSrchdgIDLPLVFRECIDYVEKHGMKCEGIYKVSGIKSKVDELKAAYNrresPNLEEYEP---PTVASLL 78

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907204050 559 LIFLEALPEPVICYELYQRCLDSAHDPRI------CKQVISQLPRCHRNVFRYLMAFLRELLKFSDYNNINTNMIATLFS 632
Cdd:cd04381    79 KQYLRELPEPLLTKELMPRFEEACGRPTEaereqeLQRLLKELPECNRLLLAWLIVHMDHVIAQELETKMNIQNISIVLS 158
 
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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