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Conserved domains on  [gi|30231213|ref|NP_032411|]
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type II inositol 1,4,5-trisphosphate 5-phosphatase precursor [Mus musculus]

Protein Classification

INPP5c_INPP5B and RhoGAP_OCRL1 domain-containing protein( domain architecture ID 11245537)

protein containing domains PH_OCRL2, INPP5c_INPP5B, and RhoGAP_OCRL1

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 ...
 345-638 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: 564.63  E-value: 0e+00
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 30231213 345 FRFFVGTYNVNGQSPKECLRPWLSHSALAPDVYCVGFQELDLSKEAFFFHDTPKEEEWFKAVSESLHPDAKYAKVKFVRL 424
Cdd:cd09093   1 FRIFVGTWNVNGQSPDESLRPWLSCDEEPPDIYAIGFQELDLSAEAFLFNDSSREQEWVKAVERGLHPDAKYKKVKLIRL 80

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 30231213 425 VGIMLLLYVKQEHAAYISEVEAETVGTGIMGRMGNKGGVAIRFQLHNTSICVVNSHLAAHTEEYERRNQDYRDICSRMQF 504
Cdd:cd09093  81 VGMMLLVFVKKEHRQHIKEVAAETVGTGIMGKMGNKGGVAVRFQFHNTTFCFVNSHLAAHMEEVERRNQDYKDICARMKF 160

                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 30231213 505 PqvDPSQPPLTINKHDVILWLGDLNYRIEELDVGKVKKLVEEKAFQTLYAHDQLKIQVAARTIFDGFTEGEITFQPTYKY 584
Cdd:cd09093 161 E--DPDGPPLSISDHDVVFWLGDLNYRIQELPTEEVKELIEKNDLEELLKYDQLNIQRRAGKVFEGFTEGEINFIPTYKY 238

                       250       260       270       280       290
                ....*....|....*....|....*....|....*....|....*....|....
gi 30231213 585 DTGSDDWDTSEKCRAPAWCDRILWKGKNITQLSYQSHMALKTSDHKPVSSVFDI 638
Cdd:cd09093 239 DPGTDNWDSSEKCRAPAWCDRILWRGTNIVQLSYRSHMELKTSDHKPVSALFDI 292
RhoGAP_OCRL1 cd04380
RhoGAP_OCRL1: RhoGAP (GTPase-activator protein [GAP] for Rho-like small GTPases) domain ...
 772-990 2.19e-78

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: 254.96  E-value: 2.19e-78
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 30231213 772 FLSVSGNYLPSCFGSPIHTLCYMREPILDLPlktVSDLTLMSVQTADDRsqlenPMEIPKELWMMVDYLYRNAVQQEDLF 851
Cdd:cd04380   1 FITVTGVYLPSCFGSSLETLIRLPDPGIRNL---IDQLELGDNPDYSEV-----PLSIPKEIWRLVDYLYTRGLAQEGLF 72

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 30231213 852 QQPGLR----PEFDHIRDCLDTGMIDQLCANNHSVAEALLLFLESLPEPVICYSAYHSCLEC-SGNYAASKQII-LTLPS 925
Cdd:cd04380  73 EEPGLPsepgELLAEIRDALDTGSPFNSPGSAESVAEALLLFLESLPDPIIPYSLYERLLEAvANNEEDKRQVIrISLPP 152

                       170       180       190       200       210       220
                ....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 30231213 926 FHKNVFNYLMAFLQELLKNSANNHLDENILASIFGSLLLRNPARHQ-KLDMAEKKKAQEFIHQFLC 990
Cdd:cd04380 153 VHRNVFVYLCSFLRELLSESADRGLDENTLATIFGRVLLRDPPRAGgKERRAERDRKRAFIEQFLL 218
INPP5B_PH pfam16776
Type II inositol 1,4,5-trisphosphate 5-phosphatase PH domain;
1-146 3.10e-71

Type II inositol 1,4,5-trisphosphate 5-phosphatase PH domain;


:

Pssm-ID: 465268  Cd Length: 142  Bit Score: 232.21  E-value: 3.10e-71
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 30231213     1 MDQSVAIQETLVEGEYCVIAVQGVLCKGDSRQSRLLGLVRYrlendAQEHALFLYTHRRMAITGDDVSLDQIVPLSKDFM 80
Cdd:pfam16776   1 MDQSAAIQETLAEGENCLAAVQGVLIQGDSTQSRLLGLVES-----NNEHALFLYTHRRMAITGEDLSLEDVVPIDEDFK 75

                          90       100       110       120       130       140
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 30231213    81 LEEVSPDGELYILGSDVTVQLNTAELKLVFQLPFGSHTRTFLQEVARACPG-FDPETRDPEFEWLSR 146
Cdd:pfam16776  76 CEEVSSPAELDVIGSDTTVRLSSRERELELELPFGSHTRLFLSEVNRAWSGvALKASPPPDFLWLSK 142
 
Name Accession Description Interval E-value
INPP5c_INPP5B cd09093
Catalytic inositol polyphosphate 5-phosphatase (INPP5c) domain of Type II inositol ...
 345-638 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: 564.63  E-value: 0e+00
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 30231213 345 FRFFVGTYNVNGQSPKECLRPWLSHSALAPDVYCVGFQELDLSKEAFFFHDTPKEEEWFKAVSESLHPDAKYAKVKFVRL 424
Cdd:cd09093   1 FRIFVGTWNVNGQSPDESLRPWLSCDEEPPDIYAIGFQELDLSAEAFLFNDSSREQEWVKAVERGLHPDAKYKKVKLIRL 80

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 30231213 425 VGIMLLLYVKQEHAAYISEVEAETVGTGIMGRMGNKGGVAIRFQLHNTSICVVNSHLAAHTEEYERRNQDYRDICSRMQF 504
Cdd:cd09093  81 VGMMLLVFVKKEHRQHIKEVAAETVGTGIMGKMGNKGGVAVRFQFHNTTFCFVNSHLAAHMEEVERRNQDYKDICARMKF 160

                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 30231213 505 PqvDPSQPPLTINKHDVILWLGDLNYRIEELDVGKVKKLVEEKAFQTLYAHDQLKIQVAARTIFDGFTEGEITFQPTYKY 584
Cdd:cd09093 161 E--DPDGPPLSISDHDVVFWLGDLNYRIQELPTEEVKELIEKNDLEELLKYDQLNIQRRAGKVFEGFTEGEINFIPTYKY 238

                       250       260       270       280       290
                ....*....|....*....|....*....|....*....|....*....|....
gi 30231213 585 DTGSDDWDTSEKCRAPAWCDRILWKGKNITQLSYQSHMALKTSDHKPVSSVFDI 638
Cdd:cd09093 239 DPGTDNWDSSEKCRAPAWCDRILWRGTNIVQLSYRSHMELKTSDHKPVSALFDI 292
IPPc smart00128
Inositol polyphosphate phosphatase, catalytic domain homologues; Mg(2+)-dependent/Li(+) ...
 343-640 5.49e-112

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


Pssm-ID: 214525 [Multi-domain]  Cd Length: 306  Bit Score: 347.80  E-value: 5.49e-112
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 30231213    343 QNFRFFVGTYNVNGQS-PKECLRPWLSHSALA-----PDVYCVGFQELDLSKE-AFFFHDTPKEEEWFKAVSESLHPDAK 415
Cdd:smart00128   1 RDIKVLIGTWNVGGLEsPKVDVTSWLFQKIEVkqsekPDIYVIGLQEVVGLAPgVILETIAGKERLWSDLLESSLNGDGQ 80

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 30231213    416 YAKVKFVRLVGIMLLLYVKQEHAAYISEVEAETVGTGIMGRMGNKGGVAIRFQLHNTSICVVNSHLAAHTEEYERRNQDY 495
Cdd:smart00128  81 YNVLAKVYLVGILVLVFVKANHLVYIKDVETFTVKTGMGGLWGNKGAVAVRFKLSDTSFCFVNSHLAAGASNVEQRNQDY 160

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 30231213    496 RDICSRMQFPQVdpsqPPLTINKHDVILWLGDLNYRIEELDVGKVKKLVEEKAFQTLYAHDQLKIQVAARTIFDGFTEGE 575
Cdd:smart00128 161 KTILRALSFPER----ALLSQFDHDVVFWFGDLNFRLDSPSYEEVRRKISKKEFDDLLEKDQLNRQREAGKVFKGFQEGP 236

                          250       260       270       280       290       300
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 30231213    576 ITFQPTYKYDT-GSDDWDTSEKCRAPAWCDRILWK--GKNITQLS-YQSHMALKTSDHKPVSSVFDIGV 640
Cdd:smart00128 237 ITFPPTYKYDSvGTETYDTSEKKRVPAWCDRILYRsnGPELIQLSeYHSGMEITTSDHKPVFATFRLKV 305
RhoGAP_OCRL1 cd04380
RhoGAP_OCRL1: RhoGAP (GTPase-activator protein [GAP] for Rho-like small GTPases) domain ...
 772-990 2.19e-78

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: 254.96  E-value: 2.19e-78
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 30231213 772 FLSVSGNYLPSCFGSPIHTLCYMREPILDLPlktVSDLTLMSVQTADDRsqlenPMEIPKELWMMVDYLYRNAVQQEDLF 851
Cdd:cd04380   1 FITVTGVYLPSCFGSSLETLIRLPDPGIRNL---IDQLELGDNPDYSEV-----PLSIPKEIWRLVDYLYTRGLAQEGLF 72

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 30231213 852 QQPGLR----PEFDHIRDCLDTGMIDQLCANNHSVAEALLLFLESLPEPVICYSAYHSCLEC-SGNYAASKQII-LTLPS 925
Cdd:cd04380  73 EEPGLPsepgELLAEIRDALDTGSPFNSPGSAESVAEALLLFLESLPDPIIPYSLYERLLEAvANNEEDKRQVIrISLPP 152

                       170       180       190       200       210       220
                ....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 30231213 926 FHKNVFNYLMAFLQELLKNSANNHLDENILASIFGSLLLRNPARHQ-KLDMAEKKKAQEFIHQFLC 990
Cdd:cd04380 153 VHRNVFVYLCSFLRELLSESADRGLDENTLATIFGRVLLRDPPRAGgKERRAERDRKRAFIEQFLL 218
INPP5B_PH pfam16776
Type II inositol 1,4,5-trisphosphate 5-phosphatase PH domain;
1-146 3.10e-71

Type II inositol 1,4,5-trisphosphate 5-phosphatase PH domain;


Pssm-ID: 465268  Cd Length: 142  Bit Score: 232.21  E-value: 3.10e-71
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 30231213     1 MDQSVAIQETLVEGEYCVIAVQGVLCKGDSRQSRLLGLVRYrlendAQEHALFLYTHRRMAITGDDVSLDQIVPLSKDFM 80
Cdd:pfam16776   1 MDQSAAIQETLAEGENCLAAVQGVLIQGDSTQSRLLGLVES-----NNEHALFLYTHRRMAITGEDLSLEDVVPIDEDFK 75

                          90       100       110       120       130       140
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 30231213    81 LEEVSPDGELYILGSDVTVQLNTAELKLVFQLPFGSHTRTFLQEVARACPG-FDPETRDPEFEWLSR 146
Cdd:pfam16776  76 CEEVSSPAELDVIGSDTTVRLSSRERELELELPFGSHTRLFLSEVNRAWSGvALKASPPPDFLWLSK 142
COG5411 COG5411
Phosphatidylinositol 5-phosphate phosphatase [Signal transduction mechanisms];
332-646 3.09e-68

Phosphatidylinositol 5-phosphate phosphatase [Signal transduction mechanisms];


Pssm-ID: 227698 [Multi-domain]  Cd Length: 460  Bit Score: 235.83  E-value: 3.09e-68
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 30231213 332 LVQKEENYTYIQNFRFFVGTYNVNGQSPKECLRPWLSHSALA---PDVYCVGFQE-LDLSKEAFFFHDT-PKEEEWFKAV 406
Cdd:COG5411  17 LRQRRSKYVIEKDVSIFVSTFNPPGKPPKASTKRWLFPEIEAtelADLYVVGLQEvVELTPGSILSADPyDRLRIWESKV 96

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 30231213 407 SESLHP---DAKYAKVKFVRLVGIMLLLYVKQEHAAYISEVEAETVGTGIMGRMGNKGGVAIRFQLHNTSICVVNSHLAA 483
Cdd:COG5411  97 LDCLNGaqsDEKYSLLRSPQLGGILLRVFSLATNLPVVKPVSGTVKKTGFGGSSSNKGAVAIRFNYERTSFCFVNSHLAA 176

                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 30231213 484 HTEEYERRNQDYRDICSRMQFPQvdpsqpPLTINKHDVILWLGDLNYRIEeLDVGKVKKLVE--EKAFQTLYAHDQLKIQ 561
Cdd:COG5411 177 GVNNIEERIFDYRSIASNICFSR------GLRIYDHDTIFWLGDLNYRVT-STNEEVRPEIAsdDGRLDKLFEYDQLLWE 249

                       250       260       270       280       290       300       310       320
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 30231213 562 VAARTIFDGFTEGEITFQPTYKYDTGSDDWDTSEKCRAPAWCDRILWKGKNITQLSYQSHMALKTSDHKPVSSVFDIGVR 641
Cdd:COG5411 250 MEVGNVFPGFKEPVITFPPTYKFDYGTDEYDTSDKGRIPSWTDRILYKSEQLTPHSYSSIPHLMISDHRPVYATFRAKIK 329


                ....*
gi 30231213 642 VVNEE 646
Cdd:COG5411 330 VVDPS 334
PLN03191 PLN03191
Type I inositol-1,4,5-trisphosphate 5-phosphatase 2; Provisional
 393-652 7.19e-59

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


Pssm-ID: 215624 [Multi-domain]  Cd Length: 621  Bit Score: 213.62  E-value: 7.19e-59
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 30231213  393 FHDTPKEEEWFKAVSESLHPDAKYAKVKFVRLVGIMLLLYVKQEHAAYISEVEAETVGTGIMGRMGNKGGVAIRFQLHNT 472
Cdd:PLN03191 341 FKEVPSYQLPEDLIKDCRKVKQKYVRIVSKQMVGIYVSVWVRKRLRRHINNLKVSPVGVGLMGYMGNKGSVSISMSLFQS 420

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 30231213  473 SICVVNSHLAA-HTEEYE-RRNQDYRDICSRMQFPQVDPSQPPLTINKHDVILWLGDLNYRIEELDvGKVKKLVEEKAFQ 550
Cdd:PLN03191 421 RLCFVCSHLTSgHKDGAEqRRNADVYEIIRRTRFSSVLDTDQPQTIPSHDQIFWFGDLNYRLNMLD-TEVRKLVAQKRWD 499

                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 30231213  551 TLYAHDQLKIQVAARTIFDGFTEGEITFQPTYKYDTGSDDW-----DTSEKCRAPAWCDRILWKGKNITQLSYQsHMALK 625
Cdd:PLN03191 500 ELINSDQLIKELRSGHVFDGWKEGPIKFPPTYKYEINSDRYvgenpKEGEKKRSPAWCDRILWLGKGIKQLCYK-RSEIR 578

                        250       260
                 ....*....|....*....|....*..
gi 30231213  626 TSDHKPVSSVFDIGVRVVNEELYRKTL 652
Cdd:PLN03191 579 LSDHRPVSSMFLVEVEVFDHRKLQRAL 605
PH_OCRL2 cd13383
oculocerebrorenal syndrome of Lowe 2 Pleckstrin homology-like domain; OCRL2 ( also called ...
 17-129 2.86e-56

oculocerebrorenal syndrome of Lowe 2 Pleckstrin homology-like domain; OCRL2 ( also called IPNNB5, inositol polyphosphate-5-phosphatase, phosphoinositide 5-phosphatase, 5PTase, or type II inositol-1,4,5-trisphosphate 5-phosphatase) hydrolyzes phosphatidylinositol 4,5-bisphosphate (PtIns(4,5)P2) and the signaling molecule phosphatidylinositol 1,4,5-trisphosphate (PtIns(1,4,5)P3), and thereby modulates cellular signaling events. It interact with APPL1, FAM109A and FAM109B and several Rab GTPases which might both target them to the specific membranes and as well as stimulating the phosphatase activity. OCRL2 contains a PH domain and a Rho-GAP domain. PH domains have diverse functions, but in general are involved in targeting proteins to the appropriate cellular location or in the interaction with a binding partner. They share little sequence conservation, but all have a common fold, which is electrostatically polarized. Less than 10% of PH domains bind phosphoinositide phosphates (PIPs) with high affinity and specificity. PH domains are distinguished from other PIP-binding domains by their specific high-affinity binding to PIPs with two vicinal phosphate groups: PtdIns(3,4)P2, PtdIns(4,5)P2 or PtdIns(3,4,5)P3 which results in targeting some PH domain proteins to the plasma membrane. A few display strong specificity in lipid binding. Any specificity is usually determined by loop regions or insertions in the N-terminus of the domain, which are not conserved across all PH domains. PH domains are found in cellular signaling proteins such as serine/threonine kinase, tyrosine kinases, regulators of G-proteins, endocytotic GTPases, adaptors, as well as cytoskeletal associated molecules and in lipid associated enzymes.


Pssm-ID: 270183  Cd Length: 108  Bit Score: 189.34  E-value: 2.86e-56
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 30231213  17 CVIAVQGVLCKGDSRQSRLLGLVRYRlendaQEHALFLYTHRRMAITGDDVSLDQIVPLSKDFMLEEVSPDGELYILGSD 96
Cdd:cd13383   1 CEIAVQGSLIQGWSKASRLLGLVNKR-----TTHALVIYTHRRMAITYSDVTLERILPIDQDFKCEEVTDDSDLQQDGSD 75

                        90       100       110
                ....*....|....*....|....*....|...
gi 30231213  97 VTVQLNTAELKLVFQLPFGSHTRTFLQEVARAC 129
Cdd:cd13383  76 VTVNVTSAKLHLVFEMRPGSVTSSLVSEIFRAI 108
RhoGAP smart00324
GTPase-activator protein for Rho-like GTPases; GTPase activator proteins towards Rho/Rac ...
 828-989 7.92e-37

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: 136.63  E-value: 7.92e-37
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 30231213    828 EIPKELWMMVDYLYRNAVQQEDLFQQPGLRPEFDHIRDCLDTGMIDQLC---ANNHSVAEALLLFLESLPEPVICYSAYH 904
Cdd:smart00324   2 PIPIIVEKCIEYLEKRGLDTEGIYRVSGSKSRVKELRDAFDSGPDPDLDlseYDVHDVAGLLKLFLRELPEPLITYELYE 81

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 30231213    905 SCLECSGN------YAASKQIILTLPSFHKNVFNYLMAFLQELLKNSANNHLDENILASIFGSLLLRNPArHQKLDMAEK 978
Cdd:smart00324  82 EFIEAAKLedeterLRALRELLSLLPPANRATLRYLLAHLNRVAEHSEENKMTARNLAIVFGPTLLRPPD-GEVASLKDI 160

                          170
                   ....*....|.
gi 30231213    979 KKAQEFIHQFL 989
Cdd:smart00324 161 RHQNTVIEFLI 171
RhoGAP pfam00620
RhoGAP domain; GTPase activator proteins towards Rho/Rac/Cdc42-like small GTPases.
 830-968 1.30e-34

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


Pssm-ID: 459875  Cd Length: 148  Bit Score: 129.20  E-value: 1.30e-34
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 30231213   830 PKELWMMVDYLYRNAVQQEDLFQQPGLRPEFDHIRDCLDTG---MIDQLCANNHSVAEALLLFLESLPEPVICYSAYHSC 906
Cdd:pfam00620   1 PLIVRKCVEYLEKRGLDTEGIFRVSGSASRIKELREAFDRGpdvDLDLEEEDVHVVASLLKLFLRELPEPLLTFELYEEF 80

                          90       100       110       120       130       140
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 30231213   907 LEC------SGNYAASKQIILTLPSFHKNVFNYLMAFLQELLKNSANNHLDENILASIFGSLLLRNPA 968
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 ...
 345-638 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: 564.63  E-value: 0e+00
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 30231213 345 FRFFVGTYNVNGQSPKECLRPWLSHSALAPDVYCVGFQELDLSKEAFFFHDTPKEEEWFKAVSESLHPDAKYAKVKFVRL 424
Cdd:cd09093   1 FRIFVGTWNVNGQSPDESLRPWLSCDEEPPDIYAIGFQELDLSAEAFLFNDSSREQEWVKAVERGLHPDAKYKKVKLIRL 80

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 30231213 425 VGIMLLLYVKQEHAAYISEVEAETVGTGIMGRMGNKGGVAIRFQLHNTSICVVNSHLAAHTEEYERRNQDYRDICSRMQF 504
Cdd:cd09093  81 VGMMLLVFVKKEHRQHIKEVAAETVGTGIMGKMGNKGGVAVRFQFHNTTFCFVNSHLAAHMEEVERRNQDYKDICARMKF 160

                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 30231213 505 PqvDPSQPPLTINKHDVILWLGDLNYRIEELDVGKVKKLVEEKAFQTLYAHDQLKIQVAARTIFDGFTEGEITFQPTYKY 584
Cdd:cd09093 161 E--DPDGPPLSISDHDVVFWLGDLNYRIQELPTEEVKELIEKNDLEELLKYDQLNIQRRAGKVFEGFTEGEINFIPTYKY 238

                       250       260       270       280       290
                ....*....|....*....|....*....|....*....|....*....|....
gi 30231213 585 DTGSDDWDTSEKCRAPAWCDRILWKGKNITQLSYQSHMALKTSDHKPVSSVFDI 638
Cdd:cd09093 239 DPGTDNWDSSEKCRAPAWCDRILWRGTNIVQLSYRSHMELKTSDHKPVSALFDI 292
INPP5c cd09074
Catalytic domain of inositol polyphosphate 5-phosphatases; Inositol polyphosphate ...
 345-638 1.17e-136

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: 412.11  E-value: 1.17e-136
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 30231213 345 FRFFVGTYNVNGQ-SPKECLRPWLS-HSALAPDVYCVGFQELDLSKEAFF-FHDTPKEEEWFKAVSESLHPDAKYAKVKF 421
Cdd:cd09074   1 VKIFVVTWNVGGGiSPPENLENWLSpKGTEAPDIYAVGVQEVDMSVQGFVgNDDSAKAREWVDNIQEALNEKENYVLLGS 80

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 30231213 422 VRLVGIMLLLYVKQEHAAYIS--EVEAETVGTGIMGRMGNKGGVAIRFQLHNTSICVVNSHLAAHTEEYERRNQDYRDIC 499
Cdd:cd09074  81 AQLVGIFLFVFVKKEHLPQIKdlEVEGVTVGTGGGGKLGNKGGVAIRFQINDTSFCFVNSHLAAGQEEVERRNQDYRDIL 160

                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 30231213 500 SRMQFPQvdPSQPPLTINKHDVILWLGDLNYRIEELDVgKVKKLVEEKAFQTLYAHDQLKIQVAARTIFDGFTEGEITFQ 579
Cdd:cd09074 161 SKLKFYR--GDPAIDSIFDHDVVFWFGDLNYRIDSTDD-EVRKLISQGDLDDLLEKDQLKKQKEKGKVFDGFQELPITFP 237

                       250       260       270       280       290       300
                ....*....|....*....|....*....|....*....|....*....|....*....|..
gi 30231213 580 PTYKYDTGSDDWDTSEKCRAPAWCDRILWK---GKNITQLSYQSHMALKTSDHKPVSSVFDI 638
Cdd:cd09074 238 PTYKFDPGTDEYDTSDKKRIPAWCDRILYKskaGSEIQPLSYTSVPLYKTSDHKPVRATFRV 299
IPPc smart00128
Inositol polyphosphate phosphatase, catalytic domain homologues; Mg(2+)-dependent/Li(+) ...
 343-640 5.49e-112

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


Pssm-ID: 214525 [Multi-domain]  Cd Length: 306  Bit Score: 347.80  E-value: 5.49e-112
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 30231213    343 QNFRFFVGTYNVNGQS-PKECLRPWLSHSALA-----PDVYCVGFQELDLSKE-AFFFHDTPKEEEWFKAVSESLHPDAK 415
Cdd:smart00128   1 RDIKVLIGTWNVGGLEsPKVDVTSWLFQKIEVkqsekPDIYVIGLQEVVGLAPgVILETIAGKERLWSDLLESSLNGDGQ 80

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 30231213    416 YAKVKFVRLVGIMLLLYVKQEHAAYISEVEAETVGTGIMGRMGNKGGVAIRFQLHNTSICVVNSHLAAHTEEYERRNQDY 495
Cdd:smart00128  81 YNVLAKVYLVGILVLVFVKANHLVYIKDVETFTVKTGMGGLWGNKGAVAVRFKLSDTSFCFVNSHLAAGASNVEQRNQDY 160

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 30231213    496 RDICSRMQFPQVdpsqPPLTINKHDVILWLGDLNYRIEELDVGKVKKLVEEKAFQTLYAHDQLKIQVAARTIFDGFTEGE 575
Cdd:smart00128 161 KTILRALSFPER----ALLSQFDHDVVFWFGDLNFRLDSPSYEEVRRKISKKEFDDLLEKDQLNRQREAGKVFKGFQEGP 236

                          250       260       270       280       290       300
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 30231213    576 ITFQPTYKYDT-GSDDWDTSEKCRAPAWCDRILWK--GKNITQLS-YQSHMALKTSDHKPVSSVFDIGV 640
Cdd:smart00128 237 ITFPPTYKYDSvGTETYDTSEKKRVPAWCDRILYRsnGPELIQLSeYHSGMEITTSDHKPVFATFRLKV 305
INPP5c_ScInp51p-like cd09090
Catalytic inositol polyphosphate 5-phosphatase (INPP5c) domain of Saccharomyces cerevisiae ...
 346-636 7.68e-93

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: 296.56  E-value: 7.68e-93
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 30231213 346 RFFVGTYNVNGQSPKECLRPWLSHSAL--APDVYCVGFQEL-DLSKEAFFFHDTPKEEEWFKAVSESLhpdAKYAKVKFV 422
Cdd:cd09090   2 NIFVGTFNVNGKSYKDDLSSWLFPEENdeLPDIVVIGLQEVvELTAGQILNSDPSKSSFWEKKIKTTL---NGRGGEKYV 78

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 30231213 423 RL-----VGIMLLLYVKQEHAAYISEVEAETVGTGIMGRMGNKGGVAIRFQLHNTSICVVNSHLAAHTEEYERRNQDYRD 497
Cdd:cd09090  79 LLrseqlVGTALLFFVKESQLPKVKNVEGSTKKTGLGGMSGNKGAVAIRFDYGDTSFCFVTSHLAAGLTNYEERNNDYKT 158

                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 30231213 498 ICSRMQFPQvdpsqpPLTINKHDVILWLGDLNYRIEeLDVGKVKKLVEEKAFQTLYAHDQLKIQVAARTIFDGFTEGEIT 577
Cdd:cd09090 159 IARGLRFSR------GRTIKDHDHVIWLGDFNYRIS-LTNEDVRRFILNGKLDKLLEYDQLNQQMNAGEVFPGFSEGPIT 231

                       250       260       270       280       290
                ....*....|....*....|....*....|....*....|....*....|....*....
gi 30231213 578 FQPTYKYDTGSDDWDTSEKCRAPAWCDRILWKGKNITQLSYQSHMaLKTSDHKPVSSVF 636
Cdd:cd09090 232 FPPTYKYDKGTDNYDTSEKQRIPAWTDRILYRGENLRQLSYNSAP-LRFSDHRPVYATF 289
INPP5c_INPP5J-like cd09094
Catalytic inositol polyphosphate 5-phosphatase (INPP5c) domain of inositol polyphosphate ...
 345-638 9.74e-92

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: 293.89  E-value: 9.74e-92
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 30231213 345 FRFFVGTYNVNGQSPKECLRPWL--SHSALAPDVYCVGFQELDlSKEAFFFHDTPKEEEWFKAVSESLHPDaKYAKVKFV 422
Cdd:cd09094   1 LRVYVVTWNVATAPPPIDVRSLLglQSPEVAPDIYIIGLQEVN-SKPVQFVSDLIFDDPWSDLFMDILSPK-GYVKVSSI 78

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 30231213 423 RLVGIMLLLYVKQEHAAYISEVEAETVGTGIMGRMGNKGGVAIRFQLHNTSICVVNSHLAAHTEEYERRNQDYRDICSRM 502
Cdd:cd09094  79 RLQGLLLLVFVKIQHLPFIRDVQTNYTRTGLGGYWGNKGAVTVRFSLYGHMICFLNCHLPAHMEKWEQRIDDFETILSTQ 158

                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 30231213 503 QFPQVDPSqpplTINKHDVILWLGDLNYRIEELDVGKVKKLVEEKAFQTLYAHDQLKIQVAARTIFDGFTEGEITFQPTY 582
Cdd:cd09094 159 VFNECNTP----SILDHDYVFWFGDLNFRIEDVSIEFVRELVNSKKYHLLLEKDQLNMAKRKEEAFQGFQEGPLNFAPTY 234

                       250       260       270       280       290       300
                ....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 30231213 583 KYDTGSDDWDTSEKCRAPAWCDRILWKGK----------NITQLSYQSHMALKTSDHKPVSSVFDI 638
Cdd:cd09094 235 KFDLGTDEYDTSGKKRKPAWTDRILWKVNpdasteekflSITQTSYKSHMEYGISDHKPVTAQFRL 300
INPP5c_Synj cd09089
Catalytic inositol polyphosphate 5-phosphatase (INPP5c) domain of synaptojanins; This ...
 346-638 9.18e-89

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: 286.98  E-value: 9.18e-89
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 30231213 346 RFFVGTYNVNGQS-------PKECLRPWLSHSALA--------------PDVYCVGFQEL-DLSKEAFFFHDTPKEEEWF 403
Cdd:cd09089   2 RVFVGTWNVNGGKhfrsiafKHQSMTDWLLDNPKLagqcsndseedekpVDIFAIGFEEMvDLNASNIVSASTTNQKEWG 81

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 30231213 404 KAVSESLHPDAKYAKVKFVRLVGIMLLLYVKQEHAAYISEVEAETVGTGIMGRMGNKGGVAIRFQLHNTSICVVNSHLAA 483
Cdd:cd09089  82 EELQKTISRDHKYVLLTSEQLVGVCLFVFVRPQHAPFIRDVAVDTVKTGLGGAAGNKGAVAIRFLLHSTSLCFVCSHFAA 161

                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 30231213 484 HTEEYERRNQDYRDICSRMQFPQvdpsqpPLTINKHDVILWLGDLNYRIEeLDVGKVKKLVEEKAFQTLYAHDQLKIQVA 563
Cdd:cd09089 162 GQSQVKERNEDFAEIARKLSFPM------GRTLDSHDYVFWCGDFNYRID-LPNDEVKELVRNGDWLKLLEFDQLTKQKA 234

                       250       260       270       280       290       300       310       320
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 30231213 564 ARTIFDGFTEGEITFQPTYKYDTGSDDWDTSEKCRAPAWCDRILWKGK-------------------NITQLSYQSHMAL 624
Cdd:cd09089 235 AGNVFKGFLEGEINFAPTYKYDLFSDDYDTSEKCRTPAWTDRVLWRRRkwpsdkteeslvetndptwNPGTLLYYGRAEL 314

                       330
                ....*....|....
gi 30231213 625 KTSDHKPVSSVFDI 638
Cdd:cd09089 315 KTSDHRPVVAIIDI 328
RhoGAP_OCRL1 cd04380
RhoGAP_OCRL1: RhoGAP (GTPase-activator protein [GAP] for Rho-like small GTPases) domain ...
 772-990 2.19e-78

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: 254.96  E-value: 2.19e-78
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 30231213 772 FLSVSGNYLPSCFGSPIHTLCYMREPILDLPlktVSDLTLMSVQTADDRsqlenPMEIPKELWMMVDYLYRNAVQQEDLF 851
Cdd:cd04380   1 FITVTGVYLPSCFGSSLETLIRLPDPGIRNL---IDQLELGDNPDYSEV-----PLSIPKEIWRLVDYLYTRGLAQEGLF 72

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 30231213 852 QQPGLR----PEFDHIRDCLDTGMIDQLCANNHSVAEALLLFLESLPEPVICYSAYHSCLEC-SGNYAASKQII-LTLPS 925
Cdd:cd04380  73 EEPGLPsepgELLAEIRDALDTGSPFNSPGSAESVAEALLLFLESLPDPIIPYSLYERLLEAvANNEEDKRQVIrISLPP 152

                       170       180       190       200       210       220
                ....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 30231213 926 FHKNVFNYLMAFLQELLKNSANNHLDENILASIFGSLLLRNPARHQ-KLDMAEKKKAQEFIHQFLC 990
Cdd:cd04380 153 VHRNVFVYLCSFLRELLSESADRGLDENTLATIFGRVLLRDPPRAGgKERRAERDRKRAFIEQFLL 218
INPP5B_PH pfam16776
Type II inositol 1,4,5-trisphosphate 5-phosphatase PH domain;
1-146 3.10e-71

Type II inositol 1,4,5-trisphosphate 5-phosphatase PH domain;


Pssm-ID: 465268  Cd Length: 142  Bit Score: 232.21  E-value: 3.10e-71
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 30231213     1 MDQSVAIQETLVEGEYCVIAVQGVLCKGDSRQSRLLGLVRYrlendAQEHALFLYTHRRMAITGDDVSLDQIVPLSKDFM 80
Cdd:pfam16776   1 MDQSAAIQETLAEGENCLAAVQGVLIQGDSTQSRLLGLVES-----NNEHALFLYTHRRMAITGEDLSLEDVVPIDEDFK 75

                          90       100       110       120       130       140
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 30231213    81 LEEVSPDGELYILGSDVTVQLNTAELKLVFQLPFGSHTRTFLQEVARACPG-FDPETRDPEFEWLSR 146
Cdd:pfam16776  76 CEEVSSPAELDVIGSDTTVRLSSRERELELELPFGSHTRLFLSEVNRAWSGvALKASPPPDFLWLSK 142
COG5411 COG5411
Phosphatidylinositol 5-phosphate phosphatase [Signal transduction mechanisms];
332-646 3.09e-68

Phosphatidylinositol 5-phosphate phosphatase [Signal transduction mechanisms];


Pssm-ID: 227698 [Multi-domain]  Cd Length: 460  Bit Score: 235.83  E-value: 3.09e-68
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 30231213 332 LVQKEENYTYIQNFRFFVGTYNVNGQSPKECLRPWLSHSALA---PDVYCVGFQE-LDLSKEAFFFHDT-PKEEEWFKAV 406
Cdd:COG5411  17 LRQRRSKYVIEKDVSIFVSTFNPPGKPPKASTKRWLFPEIEAtelADLYVVGLQEvVELTPGSILSADPyDRLRIWESKV 96

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 30231213 407 SESLHP---DAKYAKVKFVRLVGIMLLLYVKQEHAAYISEVEAETVGTGIMGRMGNKGGVAIRFQLHNTSICVVNSHLAA 483
Cdd:COG5411  97 LDCLNGaqsDEKYSLLRSPQLGGILLRVFSLATNLPVVKPVSGTVKKTGFGGSSSNKGAVAIRFNYERTSFCFVNSHLAA 176

                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 30231213 484 HTEEYERRNQDYRDICSRMQFPQvdpsqpPLTINKHDVILWLGDLNYRIEeLDVGKVKKLVE--EKAFQTLYAHDQLKIQ 561
Cdd:COG5411 177 GVNNIEERIFDYRSIASNICFSR------GLRIYDHDTIFWLGDLNYRVT-STNEEVRPEIAsdDGRLDKLFEYDQLLWE 249

                       250       260       270       280       290       300       310       320
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 30231213 562 VAARTIFDGFTEGEITFQPTYKYDTGSDDWDTSEKCRAPAWCDRILWKGKNITQLSYQSHMALKTSDHKPVSSVFDIGVR 641
Cdd:COG5411 250 MEVGNVFPGFKEPVITFPPTYKFDYGTDEYDTSDKGRIPSWTDRILYKSEQLTPHSYSSIPHLMISDHRPVYATFRAKIK 329


                ....*
gi 30231213 642 VVNEE 646
Cdd:COG5411 330 VVDPS 334
INPP5c_Synj1 cd09098
Catalytic inositol polyphosphate 5-phosphatase (INPP5c) domain of synaptojanin 1; This ...
 346-638 2.49e-66

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: 226.46  E-value: 2.49e-66
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 30231213 346 RFFVGTYNVNG-------------------QSPKECLRPWLSHSALAP-DVYCVGFQEL-DLSKEAFFFHDTPKEEEWFK 404
Cdd:cd09098   2 RVCVGTWNVNGgkqfrsiafknqtltdwllDAPKKAGIPEFQDVRSKPvDIFAIGFEEMvELNAGNIVSASTTNQKLWAA 81

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 30231213 405 AVSESLHPDAKYAKVKFVRLVGIMLLLYVKQEHAAYISEVEAETVGTGIMGRMGNKGGVAIRFQLHNTSICVVNSHLAAH 484
Cdd:cd09098  82 ELQKTISRDQKYVLLASEQLVGVCLFVFIRPQHAPFIRDVAVDTVKTGMGGATGNKGAVAIRMLFHTTSLCFVCSHFAAG 161

                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 30231213 485 TEEYERRNQDYRDICSRMQFPQvdpsqpPLTINKHDVILWLGDLNYRIeELDVGKVKKLVEEKAFQTLYAHDQLKIQVAA 564
Cdd:cd09098 162 QSQVKERNEDFIEIARKLSFPM------GRMLFSHDYVFWCGDFNYRI-DIPNEEVKELIRQQNWDSLIAGDQLINQKNA 234

                       250       260       270       280       290       300       310       320
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 30231213 565 RTIFDGFTEGEITFQPTYKYDTGSDDWDTSEKCRAPAWCDRILWKGK----------------------------NITQL 616
Cdd:cd09098 235 GQVFRGFLEGKLDFAPTYKYDLFSDDYDTSEKCRTPAWTDRVLWRRRkwpfdrsaedldllnasfpdnskeqytwSPGTL 314

                       330       340
                ....*....|....*....|..
gi 30231213 617 SYQSHMALKTSDHKPVSSVFDI 638
Cdd:cd09098 315 LHYGRAELKTSDHRPVVALIDI 336
INPP5c_Synj2 cd09099
Catalytic inositol polyphosphate 5-phosphatase (INPP5c) domain of synaptojanin 2; This ...
 346-638 2.07e-62

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: 215.27  E-value: 2.07e-62
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 30231213 346 RFFVGTYNVNGQ--------SPKEcLRPWLSHS-------------ALAPDVYCVGFQEL-DLSKEAFFFHDTPKEEEWF 403
Cdd:cd09099   2 RVAMGTWNVNGGkqfrsnilGTSE-LTDWLLDSpklsgtpdfqddeSNPPDIFAVGFEEMvELSAGNIVNASTTNRKMWG 80

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 30231213 404 KAVSESLHPDAKYAKVKFVRLVGIMLLLYVKQEHAAYISEVEAETVGTGIMGRMGNKGGVAIRFQLHNTSICVVNSHLAA 483
Cdd:cd09099  81 EQLQKAISRSHRYILLTSAQLVGVCLFIFVRPYHVPFIRDVAIDTVKTGMGGKAGNKGAVAIRFQFYSTSFCFICSHLTA 160

                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 30231213 484 HTEEYERRNQDYRDICSRMQFPQVDpsqpplTINKHDVILWLGDLNYRIeELDVGKVKKLVEEKAFQTLYAHDQLKIQVA 563
Cdd:cd09099 161 GQNQVKERNEDYKEITQKLSFPMGR------NVFSHDYVFWCGDFNYRI-DLTYEEVFYFIKRQDWKKLLEFDQLQLQKS 233

                       250       260       270       280       290       300       310       320
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 30231213 564 ARTIFDGFTEGEITFQPTYKYDTGSDDWDTSEKCRAPAWCDRILWKGK----------------------NITQ------ 615
Cdd:cd09099 234 SGKIFKDFHEGTINFGPTYKYDVGSEAYDTSDKCRTPAWTDRVLWWRKkwpfektageinlldsdldfdtKIRHtwtpga 313

                       330       340
                ....*....|....*....|...
gi 30231213 616 LSYQSHMALKTSDHKPVSSVFDI 638
Cdd:cd09099 314 LMYYGRAELQASDHRPVLAIVEV 336
INPP5c_INPP5E-like cd09095
Catalytic inositol polyphosphate 5-phosphatase (INPP5c) domain of Inositol ...
 343-638 4.88e-59

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: 204.58  E-value: 4.88e-59
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 30231213 343 QNFRFFVGTYNVNGQ-SPKECLRPWL--SHSALAPDVYCVGFQEldlskeafffhDTPKEEEWFKAVSESLHPdaKYAKV 419
Cdd:cd09095   3 RNVGIFVATWNMQGQkELPENLDDFLlpTSADFAQDIYVIGVQE-----------GCSDRREWEIRLQETLGP--SHVLL 69

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 30231213 420 KFVRLVGIMLLLYVKQEHAAYISEVEAETVGTGIMGRMGNKGGVAIRFQLHNTSICVVNSHLAAHTEEYERRNQDYRDIC 499
Cdd:cd09095  70 HSASHGVLHLAVFIRRDLIWFCSEVESATVTTRIVSQIKTKGALAISFTFFGTSFLFITSHFTSGDGKVKERVLDYNKII 149

                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 30231213 500 SRMQFPQVDPSQP-------PLTinKHDVILWLGDLNYRIEElDVGKVKKLVEEKAFQT---LYAHDQLKIQVAARTIFD 569
Cdd:cd09095 150 QALNLPRNVPTNPyksesgdVTT--RFDEVFWFGDFNFRLSG-PRHLVDALINQGQEVDvsaLLQHDQLTREMSKGSIFK 226

                       250       260       270       280       290       300       310
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|..
gi 30231213 570 GFTEGEITFQPTYKYDTGSDDWDTSEKCRAPAWCDRILWKGK---NITQLSYQSHMALKTSDHKPVSSVFDI 638
Cdd:cd09095 227 GFQEAPIHFPPTYKFDIGSDVYDTSSKQRVPSYTDRILYRSRqkgDVCCLKYNSCPSIKTSDHRPVFALFRV 298
PLN03191 PLN03191
Type I inositol-1,4,5-trisphosphate 5-phosphatase 2; Provisional
 393-652 7.19e-59

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


Pssm-ID: 215624 [Multi-domain]  Cd Length: 621  Bit Score: 213.62  E-value: 7.19e-59
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 30231213  393 FHDTPKEEEWFKAVSESLHPDAKYAKVKFVRLVGIMLLLYVKQEHAAYISEVEAETVGTGIMGRMGNKGGVAIRFQLHNT 472
Cdd:PLN03191 341 FKEVPSYQLPEDLIKDCRKVKQKYVRIVSKQMVGIYVSVWVRKRLRRHINNLKVSPVGVGLMGYMGNKGSVSISMSLFQS 420

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 30231213  473 SICVVNSHLAA-HTEEYE-RRNQDYRDICSRMQFPQVDPSQPPLTINKHDVILWLGDLNYRIEELDvGKVKKLVEEKAFQ 550
Cdd:PLN03191 421 RLCFVCSHLTSgHKDGAEqRRNADVYEIIRRTRFSSVLDTDQPQTIPSHDQIFWFGDLNYRLNMLD-TEVRKLVAQKRWD 499

                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 30231213  551 TLYAHDQLKIQVAARTIFDGFTEGEITFQPTYKYDTGSDDW-----DTSEKCRAPAWCDRILWKGKNITQLSYQsHMALK 625
Cdd:PLN03191 500 ELINSDQLIKELRSGHVFDGWKEGPIKFPPTYKYEINSDRYvgenpKEGEKKRSPAWCDRILWLGKGIKQLCYK-RSEIR 578

                        250       260
                 ....*....|....*....|....*..
gi 30231213  626 TSDHKPVSSVFDIGVRVVNEELYRKTL 652
Cdd:PLN03191 579 LSDHRPVSSMFLVEVEVFDHRKLQRAL 605
PH_OCRL2 cd13383
oculocerebrorenal syndrome of Lowe 2 Pleckstrin homology-like domain; OCRL2 ( also called ...
 17-129 2.86e-56

oculocerebrorenal syndrome of Lowe 2 Pleckstrin homology-like domain; OCRL2 ( also called IPNNB5, inositol polyphosphate-5-phosphatase, phosphoinositide 5-phosphatase, 5PTase, or type II inositol-1,4,5-trisphosphate 5-phosphatase) hydrolyzes phosphatidylinositol 4,5-bisphosphate (PtIns(4,5)P2) and the signaling molecule phosphatidylinositol 1,4,5-trisphosphate (PtIns(1,4,5)P3), and thereby modulates cellular signaling events. It interact with APPL1, FAM109A and FAM109B and several Rab GTPases which might both target them to the specific membranes and as well as stimulating the phosphatase activity. OCRL2 contains a PH domain and a Rho-GAP domain. PH domains have diverse functions, but in general are involved in targeting proteins to the appropriate cellular location or in the interaction with a binding partner. They share little sequence conservation, but all have a common fold, which is electrostatically polarized. Less than 10% of PH domains bind phosphoinositide phosphates (PIPs) with high affinity and specificity. PH domains are distinguished from other PIP-binding domains by their specific high-affinity binding to PIPs with two vicinal phosphate groups: PtdIns(3,4)P2, PtdIns(4,5)P2 or PtdIns(3,4,5)P3 which results in targeting some PH domain proteins to the plasma membrane. A few display strong specificity in lipid binding. Any specificity is usually determined by loop regions or insertions in the N-terminus of the domain, which are not conserved across all PH domains. PH domains are found in cellular signaling proteins such as serine/threonine kinase, tyrosine kinases, regulators of G-proteins, endocytotic GTPases, adaptors, as well as cytoskeletal associated molecules and in lipid associated enzymes.


Pssm-ID: 270183  Cd Length: 108  Bit Score: 189.34  E-value: 2.86e-56
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 30231213  17 CVIAVQGVLCKGDSRQSRLLGLVRYRlendaQEHALFLYTHRRMAITGDDVSLDQIVPLSKDFMLEEVSPDGELYILGSD 96
Cdd:cd13383   1 CEIAVQGSLIQGWSKASRLLGLVNKR-----TTHALVIYTHRRMAITYSDVTLERILPIDQDFKCEEVTDDSDLQQDGSD 75

                        90       100       110
                ....*....|....*....|....*....|...
gi 30231213  97 VTVQLNTAELKLVFQLPFGSHTRTFLQEVARAC 129
Cdd:cd13383  76 VTVNVTSAKLHLVFEMRPGSVTSSLVSEIFRAI 108
INPP5c_SHIP cd09091
Catalytic inositol polyphosphate 5-phosphatase (INPP5c) domain of SH2 domain containing ...
 348-638 5.05e-49

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: 176.29  E-value: 5.05e-49
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 30231213 348 FVGTYNVNGQSPKECLRPWLSHSALAP-----------DVYCVGFQEldlskeafffhDTPKEEEWFKAVSESLH--PDA 414
Cdd:cd09091   4 FIGTWNMGSAPPPKNITSWFTSKGQGKtrddvadyiphDIYVIGTQE-----------DPLGEKEWLDLLRHSLKelTSL 72

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 30231213 415 KYAKVKFVRLVGIMLLLYVKQEHAAYISEVEAETVGTGIMGRMGNKGGVAIRFQLHNTSICVVNSHLAAHTEEYERRNQD 494
Cdd:cd09091  73 DYKPIAMQTLWNIRIVVLAKPEHENRISHVCTSSVKTGIANTLGNKGAVGVSFMFNGTSFGFVNSHLTSGSEKKLRRNQN 152

                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 30231213 495 YRDICSRMQFPqvDPSQPPLTIN-KHDVILWLGDLNYRIeELDVGKVKKLV---EEKAFQTLYAHDQLKIQVAARTIFDG 570
Cdd:cd09091 153 YLNILRFLSLG--DKKLSAFNIThRFTHLFWLGDLNYRL-DLPIQEAENIIqkiEQQQFEPLLRHDQLNLEREEHKVFLR 229

                       250       260       270       280       290       300       310
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 30231213 571 FTEGEITFQPTYKYDTGSDD---WD----TSEKCRAPAWCDRILWKGKNITQL---SYQSHMALKTSDHKPVSSVFDI 638
Cdd:cd09091 230 FSEEEITFPPTYRYERGSRDtyaYTkqkaTGVKYNLPSWCDRILWKSYPETHIicqSYGCTDDIVTSDHSPVFGTFEV 307
INPP5c_SHIP2-INPPL1 cd09101
Catalytic inositol polyphosphate 5-phosphatase (INPP5c) domain of SH2 domain containing ...
 348-638 1.33e-48

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: 175.16  E-value: 1.33e-48
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 30231213 348 FVGTYNVNGQSPKECLRPWLSHSALAP-----------DVYCVGFQELDLSkeafffhdtpkEEEWFKAVSESLHP--DA 414
Cdd:cd09101   4 FIGTWNMGSVPPPKSLASWLTSRGLGKtldettvtiphDIYVFGTQENSVG-----------DREWVDFLRASLKEltDI 72

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 30231213 415 KYAKVKFVRLVGIMLLLYVKQEHAAYISEVEAETVGTGIMGRMGNKGGVAIRFQLHNTSICVVNSHLAAHTEEYERRNQD 494
Cdd:cd09101  73 DYQPIALQCLWNIKMVVLVKPEHENRISHVHTSSVKTGIANTLGNKGAVGVSFMFNGTSFGFVNCHLTSGNEKTHRRNQN 152

                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 30231213 495 YRDICSRMQFPQVDPSQPPLTInKHDVILWLGDLNYRIeELDVGKVKKLVEEKAFQTLYAHDQLKIQVAARTIFDGFTEG 574
Cdd:cd09101 153 YLDILRSLSLGDKQLNAFDISL-RFTHLFWFGDLNYRL-DMDIQEILNYITRKEFDPLLAVDQLNLEREKNKVFLRFREE 230

                       250       260       270       280       290       300       310
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 30231213 575 EITFQPTYKYDTGSDD---WD----TSEKCRAPAWCDRILWKGKNITQL---SYQSHMALKTSDHKPVSSVFDI 638
Cdd:cd09101 231 EISFPPTYRYERGSRDtymWQkqktTGMRTNVPSWCDRILWKSYPETHIvcnSYGCTDDIVTSDHSPVFGTFEV 304
INPP5c_SHIP1-INPP5D cd09100
Catalytic inositol polyphosphate 5-phosphatase (INPP5c) domain of SH2 domain containing ...
 348-638 2.74e-48

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: 174.40  E-value: 2.74e-48
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 30231213 348 FVGTYNVNGQSPKECLRPWL-----------SHSALAPDVYCVGFQEldlskeafffhDTPKEEEWFKAVSESLH--PDA 414
Cdd:cd09100   4 FIGTWNMGNAPPPKKITSWFqckgqgktrddTADYIPHDIYVIGTQE-----------DPLGEKEWLDTLKHSLReiTSI 72

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 30231213 415 KYAKVKFVRLVGIMLLLYVKQEHAAYISEVEAETVGTGIMGRMGNKGGVAIRFQLHNTSICVVNSHLAAHTEEYERRNQD 494
Cdd:cd09100  73 SFKVIAIQTLWNIRIVVLAKPEHENRISHICTDSVKTGIANTLGNKGAVGVSFMFNGTSFGFVNSHLTSGSEKKLRRNQN 152

                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 30231213 495 YRDIcsrMQFPQV-DPSQPPLTI-NKHDVILWLGDLNYRIE--ELDVGKVKKLVEEKAFQTLYAHDQLKIQVAARTIFDG 570
Cdd:cd09100 153 YFNI---LRFLVLgDKKLSPFNItHRFTHLFWLGDLNYRVElpNTEAENIIQKIKQQQYQELLPHDQLLIERKESKVFLQ 229

                       250       260       270       280       290       300       310
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 30231213 571 FTEGEITFQPTYKYDTGSDDWDTSEKCRA-------PAWCDRILWKGKNITQL---SYQSHMALKTSDHKPVSSVFDI 638
Cdd:cd09100 230 FEEEEITFAPTYRFERGTRERYAYTKQKAtgmkynlPSWCDRVLWKSYPLVHVvcqSYGCTDDITTSDHSPVFATFEV 307
PH_OCRL-like cd13320
oculocerebrorenal syndrome of Lowe family Pleckstrin homology-like domain; The OCRL family has ...
 17-129 8.36e-41

oculocerebrorenal syndrome of Lowe family Pleckstrin homology-like domain; The OCRL family has two members: OCRL1 (also called INPP5F, LOCR, NPHL2, or phosphatidylinositol polyphosphate 5-phosphatase) and OCRL2 ( also called IPNNB5, inositol polyphosphate-5-phosphatase, phosphoinositide 5-phosphatase, 5PTase, or type II inositol-1,4,5-trisphosphate 5-phosphatase). The OCRL proteins hydrolyze phosphatidylinositol 4,5-bisphosphate (PtIns(4,5)P2) and the signaling molecule phosphatidylinositol 1,4,5-trisphosphate (PtIns(1,4,5)P3), and thereby modulates cellular signaling events. They interact with APPL1, FAM109A and FAM109B and several Rab GTPases which might both target them to the specific membranes and as well as stimulating the phosphatase activity. All OCRL family members contain a PH domain and a Rho-GAP domain. PH domains have diverse functions, but in general are involved in targeting proteins to the appropriate cellular location or in the interaction with a binding partner. They share little sequence conservation, but all have a common fold, which is electrostatically polarized. Less than 10% of PH domains bind phosphoinositide phosphates (PIPs) with high affinity and specificity. PH domains are distinguished from other PIP-binding domains by their specific high-affinity binding to PIPs with two vicinal phosphate groups: PtdIns(3,4)P2, PtdIns(4,5)P2 or PtdIns(3,4,5)P3 which results in targeting some PH domain proteins to the plasma membrane. A few display strong specificity in lipid binding. Any specificity is usually determined by loop regions or insertions in the N-terminus of the domain, which are not conserved across all PH domains. PH domains are found in cellular signaling proteins such as serine/threonine kinase, tyrosine kinases, regulators of G-proteins, endocytotic GTPases, adaptors, as well as cytoskeletal associated molecules and in lipid associated enzymes.


Pssm-ID: 270130  Cd Length: 105  Bit Score: 145.34  E-value: 8.36e-41
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 30231213  17 CVIAVQGVLCKGDSRQSRLLGLVRYRlendaQEHALFLYTHRRMAitgddvSLDQIVPLSKDFMLEEVSPDGEL--YILG 94
Cdd:cd13320   1 CVAAVQGVLCKGGSREPRLLSLAQRR-----GQYALIIQSHEREA------SLQDIIPINSHFRCVQEAEETLLidIASN 69

                        90       100       110
                ....*....|....*....|....*....|....*.
gi 30231213  95 SDVTVQLNTAE-LKLVFQLPFGSHTRTFLQEVARAC 129
Cdd:cd13320  70 SGCKIRLQGDEtLERLFEIPDEEHCLTFLSEVLAAQ 105
RhoGAP smart00324
GTPase-activator protein for Rho-like GTPases; GTPase activator proteins towards Rho/Rac ...
 828-989 7.92e-37

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: 136.63  E-value: 7.92e-37
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 30231213    828 EIPKELWMMVDYLYRNAVQQEDLFQQPGLRPEFDHIRDCLDTGMIDQLC---ANNHSVAEALLLFLESLPEPVICYSAYH 904
Cdd:smart00324   2 PIPIIVEKCIEYLEKRGLDTEGIYRVSGSKSRVKELRDAFDSGPDPDLDlseYDVHDVAGLLKLFLRELPEPLITYELYE 81

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 30231213    905 SCLECSGN------YAASKQIILTLPSFHKNVFNYLMAFLQELLKNSANNHLDENILASIFGSLLLRNPArHQKLDMAEK 978
Cdd:smart00324  82 EFIEAAKLedeterLRALRELLSLLPPANRATLRYLLAHLNRVAEHSEENKMTARNLAIVFGPTLLRPPD-GEVASLKDI 160

                          170
                   ....*....|.
gi 30231213    979 KKAQEFIHQFL 989
Cdd:smart00324 161 RHQNTVIEFLI 171
RhoGAP pfam00620
RhoGAP domain; GTPase activator proteins towards Rho/Rac/Cdc42-like small GTPases.
 830-968 1.30e-34

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


Pssm-ID: 459875  Cd Length: 148  Bit Score: 129.20  E-value: 1.30e-34
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 30231213   830 PKELWMMVDYLYRNAVQQEDLFQQPGLRPEFDHIRDCLDTG---MIDQLCANNHSVAEALLLFLESLPEPVICYSAYHSC 906
Cdd:pfam00620   1 PLIVRKCVEYLEKRGLDTEGIFRVSGSASRIKELREAFDRGpdvDLDLEEEDVHVVASLLKLFLRELPEPLLTFELYEEF 80

                          90       100       110       120       130       140
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 30231213   907 LEC------SGNYAASKQIILTLPSFHKNVFNYLMAFLQELLKNSANNHLDENILASIFGSLLLRNPA 968
Cdd:pfam00620  81 IEAaklpdeEERLEALRELLRKLPPANRDTLRYLLAHLNRVAQNSDVNKMNAHNLAIVFGPTLLRPPD 148
RhoGAP cd00159
RhoGAP: GTPase-activator protein (GAP) for Rho-like GTPases; GAPs towards Rho/Rac/Cdc42-like ...
 830-989 1.21e-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: 104.31  E-value: 1.21e-25
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 30231213 830 PKELWMMVDYLYRNAVQQEDLFQQPGLRPEFDHIRDCLDTGMIDQLC--ANNHSVAEALLLFLESLPEPVICYSAYHSCL 907
Cdd:cd00159   1 PLIIEKCIEYLEKNGLNTEGIFRVSGSASKIEELKKKFDRGEDIDDLedYDVHDVASLLKLYLRELPEPLIPFELYDEFI 80

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 30231213 908 ECSGNY------AASKQIILTLPSFHKNVFNYLMAFLQELLKNSANNHLDENILASIFGSLLLRNPARHQKlDMAEKKKA 981
Cdd:cd00159  81 ELAKIEdeeeriEALKELLKSLPPENRDLLKYLLKLLHKISQNSEVNKMTASNLAIVFAPTLLRPPDSDDE-LLEDIKKL 159


                ....*...
gi 30231213 982 QEFIHQFL 989
Cdd:cd00159 160 NEIVEFLI 167
RhoGAP_FAM13A1a cd04393
RhoGAP_FAM13A1a: RhoGAP (GTPase-activator protein [GAP] for Rho-like small GTPases) domain of ...
 813-960 2.08e-15

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: 75.58  E-value: 2.08e-15
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 30231213 813 SVQTADDRSQLENpmEIPKELWMMVDYLYRNAVQQEDLFQQPGLRPEFDHIRDCLDTGMIDQL--CANNHSVAEALLLFL 890
Cdd:cd04393   6 PLQELQQAGQPEN--GVPAVVRHIVEYLEQHGLEQEGLFRVNGNAETVEWLRQRLDSGEEVDLskEADVCSAASLLRLFL 83

                        90       100       110       120       130       140       150
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 30231213 891 ESLPEPVICYSAYHSCLECSGNYAAS-------KQIILTLPSFHKNVFNYLMAFLQELLKNSANNHLDENILASIFG 960
Cdd:cd04393  84 QELPEGLIPASLQIRLMQLYQDYNGEdefgrklRDLLQQLPPVNYSLLKFLCHFLSNVASQHHENRMTAENLAAVFG 160
RhoGAP_ARHGAP22_24_25 cd04390
RhoGAP_ARHGAP22_24_25: GTPase-activator protein (GAP) domain for Rho-like GTPases found in ...
 837-965 1.28e-11

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


Pssm-ID: 239855 [Multi-domain]  Cd Length: 199  Bit Score: 64.77  E-value: 1.28e-11
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 30231213 837 VDYLYRNAVQQEDLFQQPGLRPEFDHIRDCLDTGMIDQLCANN--HSVAEALLLFLESLPEPVICYSAYHSCLECS---- 910
Cdd:cd04390  30 VDFIREHGLKEEGLFRLPGQANLVKQLQDAFDAGERPSFDSDTdvHTVASLLKLYLRELPEPVIPWAQYEDFLSCAqlls 109

                        90       100       110       120       130       140
                ....*....|....*....|....*....|....*....|....*....|....*....|
gi 30231213 911 -----GNYAASKQIILtLPSFHKNVFNYLMAFLQELLKNSANNHLDENILASIFGSLLLR 965
Cdd:cd04390 110 kdeekGLGELMKQVSI-LPKVNYNLLSYICRFLDEVQSNSSVNKMSVQNLATVFGPNILR 168
RhoGAP_KIAA1688 cd04389
RhoGAP_KIAA1688: GTPase-activator protein (GAP) domain for Rho-like GTPases found in ...
 846-965 1.96e-10

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


Pssm-ID: 239854  Cd Length: 187  Bit Score: 60.87  E-value: 1.96e-10
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 30231213 846 QQEDLFQQPGLRPEFDHIRDCLDTGMI-DQLCANNHSVAEALLLFLESLPEPVICYSAYHSCLECSGNYAASKQIILTLP 924
Cdd:cd04389  39 QTEGIFRVPGDIDEVNELKLRVDQWDYpLSGLEDPHVPASLLKLWLRELEEPLIPDALYQQCISASEDPDKAVEIVQKLP 118

                        90       100       110       120
                ....*....|....*....|....*....|....*....|...
gi 30231213 925 SFHKNVFNYLMAFLQELLK--NSANNHLDENILASIFGSLLLR 965
Cdd:cd04389 119 IINRLVLCYLINFLQVFAQpeNVAHTKMDVSNLAMVFAPNILR 161
RhoGAP_srGAP cd04383
RhoGAP_srGAP: RhoGAP (GTPase-activator protein [GAP] for Rho-like small GTPases) domain ...
 828-967 3.75e-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: 57.43  E-value: 3.75e-09
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 30231213 828 EIPKELWMMVDYLYRNAVQQEDLFQQPGLRPEFDHIRDCLDTG----MIDQLCANNHSVAEALLLFLESLPEPVICYSAY 903
Cdd:cd04383  17 AIPLVVESCIRFINLYGLQHQGIFRVSGSQVEVNDIKNAFERGedplADDQNDHDINSVAGVLKLYFRGLENPLFPKERF 96

                        90       100       110       120       130       140       150
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 30231213 904 HSCLECSGNYAAS------KQIILTLPSFHKNVFNYLMAFLQELLKNSANNHLDENILASIFGSLLLRNP 967
Cdd:cd04383  97 EDLMSCVKLENPTervhqiREILSTLPRSVIIVMRYLFAFLNHLSQFSDENMMDPYNLAICFGPTLMPVP 166
EEP cd08372
Exonuclease-Endonuclease-Phosphatase (EEP) domain superfamily; This large superfamily includes ...
 349-632 1.06e-08

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


Pssm-ID: 197306 [Multi-domain]  Cd Length: 241  Bit Score: 57.11  E-value: 1.06e-08
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 30231213 349 VGTYNVNGQSPKECLRPWLSH-SALAPDVycVGFQELDLSKEAFFFHDTPKEEEWFKAVSESLHPDaKYAKVkfvrlvgi 427
Cdd:cd08372   1 VASYNVNGLNAATRASGIARWvRELDPDI--VCLQEVKDSQYSAVALNQLLPEGYHQYQSGPSRKE-GYEGV-------- 69

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 30231213 428 mlLLYVKQEHAAyISEVeaeTVGTGIMGRMGNKGGVAIRFQLHNTSICVVNSHLAAHTEEYERRNQDYRDICSRMQFpqv 507
Cdd:cd08372  70 --AILSKTPKFK-IVEK---HQYKFGEGDSGERRAVVVKFDVHDKELCVVNAHLQAGGTRADVRDAQLKEVLEFLKR--- 140

                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 30231213 508 dpsqppLTINKHDVILWLGDLNYRIEELDVGKVKKLveekafqtLYAHDQLKIQVAARTifdgftegeITFQPTykydtg 587
Cdd:cd08372 141 ------LRQPNSAPVVICGDFNVRPSEVDSENPSSM--------LRLFVALNLVDSFET---------LPHAYT------ 191

                       250       260       270       280       290
                ....*....|....*....|....*....|....*....|....*....|...
gi 30231213 588 sddWDTSEKcRAPAWCDRILW--------KGKNITQLSYQSHMAlktSDHKPV 632
Cdd:cd08372 192 ---FDTYMH-NVKSRLDYIFVsksllpsvKSSKILSDAARARIP---SDHYPI 237
RhoGAP-p50rhoGAP cd04404
RhoGAP-p50rhoGAP: RhoGAP (GTPase-activator protein [GAP] for Rho-like small GTPases) domain of ...
 813-967 1.50e-08

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: 55.81  E-value: 1.50e-08
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 30231213 813 SVQTADDRSQLENPmeIPKELWMMVDYLYRNAVQQEDLFQQPGLRPEFDHIRDCLDTGM---IDQLcANNHSVAEALLLF 889
Cdd:cd04404   9 SLQFLKEKNPEQEP--IPPVVRETVEYLQAHALTTEGIFRRSANTQVVKEVQQKYNMGEpvdFDQY-EDVHLPAVILKTF 85

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 30231213 890 LESLPEPVICYSAYH-----SCLECSGNYAASKQIILTLPSFHKNVFNYLMAFLQELLKNSANNHLDENILASIFGSLLL 964
Cdd:cd04404  86 LRELPEPLLTFDLYDdivgfLNVDKEERVERVKQLLQTLPEENYQVLKYLIKFLVQVSAHSDQNKMTNSNLAVVFGPNLL 165


                ...
gi 30231213 965 RNP 967
Cdd:cd04404 166 WAK 168
RhoGAP_chimaerin cd04372
RhoGAP_chimaerin: RhoGAP (GTPase-activator protein [GAP] for Rho-like small GTPases) domain of ...
 826-967 3.26e-08

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: 54.83  E-value: 3.26e-08
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 30231213 826 PMEIPKELWMMVDYLYRNAVQQEDLFQQPGLRPEFDHIRDCLD-----TGMIDQLCANNHSVAEALLLFLESLPEPVICY 900
Cdd:cd04372  13 NTQRPMVVDMCIREIEARGLQSEGLYRVSGFAEEIEDVKMAFDrdgekADISATVYPDINVITGALKLYFRDLPIPVITY 92

                        90       100       110       120       130       140       150
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|...
gi 30231213 901 SAYHSCLECS--GNYA----ASKQIILTLPSFHKNVFNYLMAFLQELLKNSANNHLDENILASIFGSLLLRNP 967
Cdd:cd04372  93 DTYPKFIDAAkiSNPDerleAVHEALMLLPPAHYETLRYLMEHLKRVTLHEKDNKMNAENLGIVFGPTLMRPP 165
RhoGAP_nadrin cd04386
RhoGAP_nadrin: RhoGAP (GTPase-activator protein [GAP] for Rho-like small GTPases) domain of ...
 837-964 8.77e-08

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: 53.61  E-value: 8.77e-08
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 30231213 837 VDYLYRNAVQQEDLFQQPGLRPEFDHIRDCLDTGMIDQLCA----NNHSVAEALLLFLESLPEPVICYSAYHSCLECSG- 911
Cdd:cd04386  28 VMCLLETGMNEEGLFRVGGGASKLKRLKAALDAGTFSLPLDefysDPHAVASALKSYLRELPDPLLTYNLYEDWVQAANk 107

                        90       100       110       120       130
                ....*....|....*....|....*....|....*....|....*....|....*...
gi 30231213 912 -----NYAASKQIILTLPSFHKNVFNYLMAFLQELLKNSANNHLDENILASIFGSLLL 964
Cdd:cd04386 108 pdedeRLQAIWRILNKLPRENRDNLRYLIKFLSKLAQKSDENKMSPSNIAIVLAPNLL 165
RhoGAP-ARHGAP11A cd04394
RhoGAP-ARHGAP11A: RhoGAP (GTPase-activator protein [GAP] for Rho-like small GTPases) domain of ...
 845-984 3.33e-07

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: 51.70  E-value: 3.33e-07
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 30231213 845 VQQEDLFQQPG-------LRPEFDHIRDCLDTGMIDqlcannhSVAEALLLFLESLPEPVICYSAYHSCLEC----SGNY 913
Cdd:cd04394  35 LSTEGLFRKSGsvvrqkeLKAKLEGGEACLSSALPC-------DVAGLLKQFFRELPEPLLPYDLHEALLKAqelpTDEE 107

                        90       100       110       120       130       140       150
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|...
gi 30231213 914 AASKQIILT--LPSFHKNVFNYLMAFLQELLKNSANNHLDENILASIFGSLLLRNPARHQKLDMAEKKKAQEF 984
Cdd:cd04394 108 RKSATLLLTclLPDEHVNTLRYFFSFLYDVAQRCSENKMDSSNLAVIFAPNLFQSEEGGEKMSSSTEKRLRLQ 180
RhoGAP_ARHGAP20 cd04402
RhoGAP_ARHGAP20: RhoGAP (GTPase-activator protein [GAP] for Rho-like small GTPases) domain of ...
 830-989 3.83e-07

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: 51.53  E-value: 3.83e-07
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 30231213 830 PKELWMMVDYLYRNAVQQEDLFQQPGLRPEFDHIRDCLDTGMIDQL-CANNHSVAEALLLFLESLPEPVIC---YSAYHS 905
Cdd:cd04402  16 PKPILDMLSLLYQKGPSTEGIFRRSANAKACKELKEKLNSGVEVDLkAEPVLLLASVLKDFLRNIPGSLLSsdlYEEWMS 95

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 30231213 906 CLE---CSGNYAASKQIILTLPSFHKNVFNYLMAFLQELLKNSANNHLDENILASIFGSLLLRNPARhQKLDMAEKKKAQ 982
Cdd:cd04402  96 ALDqenEEEKIAELQRLLDKLPRPNVLLLKHLICVLHNISQNSETNKMDAFNLAVCIAPSLLWPPAS-SELQNEDLKKVT 174


                ....*..
gi 30231213 983 EFIhQFL 989
Cdd:cd04402 175 SLV-QFL 180
RhoGAP_fRGD1 cd04398
RhoGAP_fRGD1: RhoGAP (GTPase-activator protein [GAP] for Rho-like small GTPases) domain of ...
 856-985 1.23e-06

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: 50.09  E-value: 1.23e-06
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 30231213 856 LRPEFDHirdclDTGMIDQLCANN-----HSVAEALLLFLESLPEPVICYSAYHSCLECSGNYAASK------QIILTLP 924
Cdd:cd04398  50 LKELFDK-----DPLNVLLISPEDyesdiHSVASLLKLFFRELPEPLLTKALSREFIEAAKIEDESRrrdalhGLINDLP 124

                        90       100       110       120       130       140
                ....*....|....*....|....*....|....*....|....*....|....*....|.
gi 30231213 925 SFHKNVFNYLMAFLQELLKNSANNHLDENILASIFGSLLLrNPARHQKLDMAEKKKAQEFI 985
Cdd:cd04398 125 DANYATLRALMFHLARIKEHESVNRMSVNNLAIIWGPTLM-NAAPDNAADMSFQSRVIETL 184
RhoGAP_ARHGAP6 cd04376
RhoGAP_ARHGAP6: RhoGAP (GTPase-activator protein [GAP] for Rho-like small GTPases) domain of ...
 825-965 4.72e-06

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: 48.59  E-value: 4.72e-06
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 30231213 825 NPME--IPKELWMMVDYLYRNAVQQEDLFQQPG-------LRPEFDHIrdcLDTGMIDQLCAnnHSVAEALLLFLESLPE 895
Cdd:cd04376   3 NPIArqVPRLVESCCQHLEKHGLQTVGIFRVGSskkrvrqLREEFDRG---IDVVLDENHSV--HDVAALLKEFFRDMPD 77

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 30231213 896 PVIC---YSAY--HSCLECSGNYAASKQIILTLPSFHKNVFNYLMAFLQELLKNSANNH-----------LDENILASIF 959
Cdd:cd04376  78 PLLPrelYTAFigTALLEPDEQLEALQLLIYLLPPCNCDTLHRLLKFLHTVAEHAADSIdedgqevsgnkMTSLNLATIF 157


                ....*.
gi 30231213 960 GSLLLR 965
Cdd:cd04376 158 GPNLLH 163
RhoGAP_ARHGAP21 cd04395
RhoGAP_ARHGAP21: RhoGAP (GTPase-activator protein [GAP] for Rho-like small GTPases) domain of ...
 880-967 6.30e-06

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: 48.17  E-value: 6.30e-06
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 30231213 880 HSVAEALLLFLESLPEPVICYSAYHSCLECSGNYAAS------KQIILTLPSFHKNVFNYLMAFLQELLKNSANNHLDEN 953
Cdd:cd04395  74 NVVSSLLKSFFRKLPEPLFTNELYPDFIEANRIEDPVerlkelRRLIHSLPDHHYETLKHLIRHLKTVADNSEVNKMEPR 153

                        90
                ....*....|....
gi 30231213 954 ILASIFGSLLLRNP 967
Cdd:cd04395 154 NLAIVFGPTLVRTS 167
RhoGAP_myosin_IX cd04377
RhoGAP_myosin_IX: RhoGAP (GTPase-activator protein [GAP] for Rho-like small GTPases) domain ...
 816-967 8.15e-06

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: 47.43  E-value: 8.15e-06
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 30231213 816 TADDRSqlenpmeIPKELWMMVDYLYRNAVQQEDLFQQPGLRPEFDHIRDCLDTGMiDQLCANN---HSVAEALLLFLES 892
Cdd:cd04377   9 TSEDRS-------VPLVLEKLLEHIEMHGLYTEGIYRKSGSANKIKELRQGLDTDP-DSVNLEDypiHVITSVLKQWLRE 80

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 30231213 893 LPEPVICYSAYHSCLECSG------NYAASKQIILTLPSFHKNVFNYLMAFLQELLKNSANNHLDENILASIFGSLLLRN 966
Cdd:cd04377  81 LPEPLMTFELYENFLRAMEleekqeRVRALYSVLEQLPRANLNTLERLIFHLVRVALQEEVNRMSANALAIVFAPCILRC 160


                .
gi 30231213 967 P 967
Cdd:cd04377 161 P 161
RhoGAP_DLC1 cd04375
RhoGAP_DLC1: RhoGAP (GTPase-activator protein [GAP] for Rho-like small GTPases) domain of ...
 829-983 1.98e-05

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


Pssm-ID: 239840  Cd Length: 220  Bit Score: 47.03  E-value: 1.98e-05
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 30231213 829 IPKELWMMVDYLYRNAVQQEDLFQQPGLRPEFDHIRDcldtgMIDQLCAN-------NHSVAEALLLFLESLPEPVIC-- 899
Cdd:cd04375  20 LPRSIQQAMRWLRNNALDQVGLFRKSGVKSRIQKLRS-----MIESSTDNvnydgqqAYDVADMLKQYFRDLPEPLLTnk 94

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 30231213 900 ----YSAYHSCLECSGNYAASKQIILTLPSFHKNVFNYLMAFLQELLKNSANNHLDENILA-----SIFGSLLLR----N 966
Cdd:cd04375  95 lsetFIAIFQYVPKEQRLEAVQCAILLLPDENREVLQTLLYFLSDVAANSQENQMTATNLAvclapSLFHLNTSRrensS 174

                       170       180
                ....*....|....*....|....*..
gi 30231213 967 PARHQKL----------DMAEKKKAQE 983
Cdd:cd04375 175 PARRMQRkkslgkpdqkELSENKAAHQ 201
INPP5A cd09092
Type I inositol polyphosphate 5-phosphatase I; Type I inositol polyphosphate 5-phosphatase I ...
 568-638 2.95e-05

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: 47.46  E-value: 2.95e-05
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 30231213 568 FDGFTEGEITFQPTYKYdtgSDDWDTSE---KCRAPAWCDRILWKgKNITQLSYQSH----------MALKTSDHKPVSS 634
Cdd:cd09092 304 KDVLYELDISFPPSYPY---SEDPEQGTqymNTRCPAWCDRILMS-HSARELKSENEeksvtydmigPNVCMGDHKPVFL 379


                ....
gi 30231213 635 VFDI 638
Cdd:cd09092 380 TFRI 383
RhoGAP_ARHGAP19 cd04392
RhoGAP_ARHGAP19: RhoGAP (GTPase-activator protein [GAP] for Rho-like small GTPases) domain of ...
 832-964 7.75e-05

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


Pssm-ID: 239857  Cd Length: 208  Bit Score: 44.76  E-value: 7.75e-05
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 30231213 832 ELWMMVDYLYRNaVQQEDLFQQPGLRPEFDHIRDCLDTGMIDQLCA---NNHSVAEALLLFLESLPEPVICYSAYHSCLE 908
Cdd:cd04392  12 QIYQLIEYLEKN-LRVEGLFRKPGNSARQQELRDLLNSGTDLDLESggfHAHDCATVLKGFLGELPEPLLTHAHYPAHLQ 90

                        90       100       110       120       130       140       150
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 30231213 909 CS--------GNYAASKQ----------IILTLPSFHKNVFNYLMAFLQELLKNSANNHLDENILASIFGSLLL 964
Cdd:cd04392  91 IAdlcqfdekGNKTSAPDkerllealqlLLLLLPEENRNLLKLILDLLYQTAKHEDKNKMSADNLALLFTPHLI 164
RhoGAP_myosin_IXB cd04407
RhoGAP_myosin_IXB: RhoGAP (GTPase-activator protein [GAP] for Rho-like small GTPases) domain ...
 821-967 9.02e-05

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: 44.60  E-value: 9.02e-05
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 30231213 821 SQLENPMEIPKELWMMVDYLYRNAVQQEDLFQQPGLRPEFDHIRDCLDTGMiDQLCANN---HSVAEALLLFLESLPEPV 897
Cdd:cd04407   7 SLTSNKTSVPIVLEKLLEHVEMHGLYTEGIYRKSGSANRMKELHQLLQADP-ENVKLENypiHAITGLLKQWLRELPEPL 85

                        90       100       110       120       130       140       150
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 30231213 898 ICYSAYHSCL------ECSGNYAASKQIILTLPSFHKNVFNYLMAFLQELLKNSANNHLDENILASIFGSLLLRNP 967
Cdd:cd04407  86 MTFAQYNDFLravelpEKQEQLQAIYRVLEQLPTANHNTLERLIFHLVKVALEEDVNRMSPNALAIVFAPCLLRCP 161
RhoGAP_GMIP_PARG1 cd04378
RhoGAP_GMIP_PARG1: RhoGAP (GTPase-activator protein [GAP] for Rho-like small GTPases) domain ...
 880-965 1.39e-04

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: 43.95  E-value: 1.39e-04
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 30231213 880 HSVAEALLLFLESLPEPVICYSAYH--------------------SCLECSGNYAASKQIILTLPSFHKNVFNYLMAFLQ 939
Cdd:cd04378  69 HDISSVLKLFLRQLPEPLILFRLYNdfialakeiqrdteedkapnTPIEVNRIIRKLKDLLRQLPASNYNTLQHLIAHLY 148

                        90       100
                ....*....|....*....|....*.
gi 30231213 940 ELLKNSANNHLDENILASIFGSLLLR 965
Cdd:cd04378 149 RVAEQFEENKMSPNNLGIVFGPTLIR 174
RhoGAP_Bcr cd04387
RhoGAP_Bcr: RhoGAP (GTPase-activator protein [GAP] for Rho-like small GTPases) domain of Bcr ...
 837-973 1.46e-04

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: 43.76  E-value: 1.46e-04
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 30231213 837 VDYLYRNAVQQEDLFQQPGLRPEFDHIRDCLDTG------MIDQLCANnhSVAEALLLFLESLPEPVIC---YSAYHSCL 907
Cdd:cd04387  24 VEEVERRGMEEVGIYRISGVATDIQALKAAFDTNnkdvsvMLSEMDVN--AIAGTLKLYFRELPEPLFTdelYPNFAEGI 101

                        90       100       110       120       130       140
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 30231213 908 ECSGNYAASK---QIILTLPSFHKNVFNYLMAFLQELLKNSANNHLDENILASIFGSLLLRNPARHQKL 973
Cdd:cd04387 102 ALSDPVAKEScmlNLLLSLPDPNLVTFLFLLHHLKRVAEREEVNKMSLHNLATVFGPTLLRPSEKESKI 170
RhoGAP_p190 cd04373
RhoGAP_p190: RhoGAP (GTPase-activator protein [GAP] for Rho-like small GTPases) domain of ...
 826-965 1.79e-04

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: 43.60  E-value: 1.79e-04
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 30231213 826 PMEIPKELWMMVDYLYRNAVQQEDLFQQPGLRPEFDHIRDCLDTGM---IDQLCANNHSVAEALLLFLESLPEPVICYSA 902
Cdd:cd04373  12 EKPIPIFLEKCVEFIEATGLETEGIYRVSGNKTHLDSLQKQFDQDHnldLVSKDFTVNAVAGALKSFFSELPDPLIPYSM 91

                        90       100       110       120       130       140
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 30231213 903 YHSCLECSG------NYAASKQIILTLPSFHKNVFNYLMAFLQELLKNSANNHLDENILASIFGSLLLR 965
Cdd:cd04373  92 HLELVEAAKindreqRLHALKELLKKFPPENFDVFKYVITHLNKVSQNSKVNLMTSENLSICFWPTLMR 160
RhoGAP_p85 cd04388
RhoGAP_p85: RhoGAP (GTPase-activator protein [GAP] for Rho-like small GTPases) domain present ...
 822-968 2.00e-04

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: 43.71  E-value: 2.00e-04
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 30231213 822 QLENPMEIPKELWMMVDYLYRNAVQQEDLF--QQPGLRPEFDHIRDClDTGMIDQLCANNHSVAEALLLFLESLPEPVIC 899
Cdd:cd04388   8 QFSPPDVAPPLLIKLVEAIEKKGLESSTLYrtQSSSSLTELRQILDC-DAASVDLEQFDVAALADALKRYLLDLPNPVIP 86

                        90       100       110       120       130       140       150
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 30231213 900 YSAYHSCLECSGNYAASKQII---------LTLPSFHKNVFNYLMAFLQELLKNSANNHLDENILASIFGSLLLRNPA 968
Cdd:cd04388  87 APVYSEMISRAQEVQSSDEYAqllrklirsPNLPHQYWLTLQYLLKHFFRLCQSSSKNLLSARALAEIFSPLLFRFQP 164
RhoGAP_CdGAP cd04384
RhoGAP_CdGAP: RhoGAP (GTPase-activator protein [GAP] for Rho-like small GTPases) domain of ...
 856-968 4.35e-04

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: 42.49  E-value: 4.35e-04
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 30231213 856 LRPEFD--HIRDCLDTGMIDQLcannHSVAEALLLFLESLPEPVICYSAYHSCLEC------SGNYAASKQIILTLPSFH 927
Cdd:cd04384  51 LRHEFDseQIPDLTKDVYIQDI----HSVSSLCKLYFRELPNPLLTYQLYEKFSEAvsaasdEERLEKIHDVIQQLPPPH 126

                        90       100       110       120
                ....*....|....*....|....*....|....*....|.
gi 30231213 928 KNVFNYLMAFLQELLKNSANNHLDENILASIFGSLLLRNPA 968
Cdd:cd04384 127 YRTLEFLMRHLSRLAKYCSITNMHAKNLAIVWAPNLLRSKQ 167
RhoGAP_GMIP cd04408
RhoGAP_GMIP: RhoGAP (GTPase-activator protein [GAP] for Rho-like small GTPases) domain of GMIP ...
 880-967 9.22e-04

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: 41.73  E-value: 9.22e-04
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 30231213 880 HSVAEALLLFLESLPEPVICYSAYHSCLECSGNYAAS------------------KQIILTLPSFHKNVFNYLMAFLQEL 941
Cdd:cd04408  69 HDITSVLKHFLKELPEPVLPFQLYDDFIALAKELQRDsekaaespsiveniirslKELLGRLPVSNYNTLRHLMAHLYRV 148

                        90       100
                ....*....|....*....|....*.
gi 30231213 942 LKNSANNHLDENILASIFGSLLLRNP 967
Cdd:cd04408 149 AERFEDNKMSPNNLGIVFGPTLLRPL 174
RhoGAP_fBEM3 cd04400
RhoGAP_fBEM3: RhoGAP (GTPase-activator [GAP] protein for Rho-like small GTPases) domain of ...
 821-964 6.02e-03

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: 38.88  E-value: 6.02e-03
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 30231213 821 SQLENPMEIPKELWMMVDYLY-RNAVQQEDLFQQPGLRPEFDHIRDCLDTGMIDQLCANN-----HSVAEALLLFLESLP 894
Cdd:cd04400  14 SHKYNGRDLPSVVYRCIEYLDkNRAIYEEGIFRLSGSASVIKQLKERFNTEYDVDLFSSSlypdvHTVAGLLKLYLRELP 93

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 30231213 895 EPVI---CYSAYHSCLECSGNYAAS----KQIILTLPSFHKNVFNYLMAFLQELLKNSANNHLDE-----------NILA 956
Cdd:cd04400  94 TLILggeLHNDFKRLVEENHDRSQRalelKDLVSQLPQANYDLLYVLFSFLRKIIEHSDVNKMNLrnvcivfsptlNIPA 173


                ....*...
gi 30231213 957 SIFGSLLL 964
Cdd:cd04400 174 GIFVLFLT 181
RhoGAP_ARHGAP27_15_12_9 cd04403
RhoGAP_ARHGAP27_15_12_9: GTPase-activator protein (GAP) domain for Rho-like GTPases found in ...
 880-966 7.26e-03

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: 38.91  E-value: 7.26e-03
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 30231213 880 HSVAEALLLFLESLPEPVICYS------------AYHSCLECSgnyaasKQIILTLPSFHKNVFNYLMAFLQELLKNSAN 947
Cdd:cd04403  71 HVITGALKLFFRELPEPLFPYSlfndfvaaiklsDYEQRVSAV------KDLIKSLPKPNHDTLKMLFRHLCRVIEHGEK 144

                        90
                ....*....|....*....
gi 30231213 948 NHLDENILASIFGSLLLRN 966
Cdd:cd04403 145 NRMTTQNLAIVFGPTLLRP 163
 
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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