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Conserved domains on  [gi|767904159|ref|XP_011539695|]
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type II inositol 1,4,5-trisphosphate 5-phosphatase isoform X2 [Homo sapiens]

Protein Classification

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

INPP5c_INPP5B and RhoGAP_OCRL1 domain-containing protein

Graphical summary

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List of domain hits

 Name Accession Description Interval E-value
INPP5c_INPP5B cd09093
Catalytic inositol polyphosphate 5-phosphatase (INPP5c) domain of Type II inositol ...
 72-365 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: 579.65  E-value: 0e+00
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767904159  72 FRFFAGTYNVNGQSPKECLRLWLSNGIQAPDVYCVGFQELDLSKEAFFFHDTPKEEEWFKAVSEGLHPDAKYAKVKLIRL 151
Cdd:cd09093    1 FRIFVGTWNVNGQSPDESLRPWLSCDEEPPDIYAIGFQELDLSAEAFLFNDSSREQEWVKAVERGLHPDAKYKKVKLIRL 80

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767904159 152 VGIMLLLYVKQEHAAYISEVEAETVGTGIMGRMGNKGGVAIRFQFHNTSICVVNSHLAAHIEEYERRNQDYKDICSRMQF 231
Cdd:cd09093   81 VGMMLLVFVKKEHRQHIKEVAAETVGTGIMGKMGNKGGVAVRFQFHNTTFCFVNSHLAAHMEEVERRNQDYKDICARMKF 160

                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767904159 232 CQPDPslPPLTISNHDVILWLGDLNYRIEELDVEKVKKLIEEKDFQMLYAYDQLKIQVAAKTVFEGFTEGELTFQPTYKY 311
Cdd:cd09093  161 EDPDG--PPLSISDHDVVFWLGDLNYRIQELPTEEVKELIEKNDLEELLKYDQLNIQRRAGKVFEGFTEGEINFIPTYKY 238

                        250       260       270       280       290
                 ....*....|....*....|....*....|....*....|....*....|....
gi 767904159 312 DTGSDDWDTSEKCRAPAWCDRILWKGKNITQLSYQSHMALKTSDHKPVSSVFDI 365
Cdd:cd09093  239 DPGTDNWDSSEKCRAPAWCDRILWRGTNIVQLSYRSHMELKTSDHKPVSALFDI 292
RhoGAP_OCRL1 cd04380
RhoGAP_OCRL1: RhoGAP (GTPase-activator protein [GAP] for Rho-like small GTPases) domain ...
 499-719 1.90e-87

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: 273.83  E-value: 1.90e-87
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767904159 499 FLSVSGNYLPSCFGSPIHTLCYMREPILDLPLETIseltlmpvWTGDDGSQLDSPMEIPKELWMMVDYLYRNAVQQEDLF 578
Cdd:cd04380    1 FITVTGVYLPSCFGSSLETLIRLPDPGIRNLIDQL--------ELGDNPDYSEVPLSIPKEIWRLVDYLYTRGLAQEGLF 72

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767904159 579 QQPGLRSE----FEHIRDCLDTGMIDNLSASNHSVAEALLLFLESLPEPVICYSTYHNCLEC-SGNYTASKQVIS-TLPI 652
Cdd:cd04380   73 EEPGLPSEpgelLAEIRDALDTGSPFNSPGSAESVAEALLLFLESLPDPIIPYSLYERLLEAvANNEEDKRQVIRiSLPP 152

                        170       180       190       200       210       220
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 767904159 653 FHKNVFHYLMAFLRELLKNSAKNHLDENILASIFGSLLLRNPAGHQ-KLDMTEKKKAQEFIHQFLCNP 719
Cdd:cd04380  153 VHRNVFVYLCSFLRELLSESADRGLDENTLATIFGRVLLRDPPRAGgKERRAERDRKRAFIEQFLLND 220
 
Name Accession Description Interval E-value
INPP5c_INPP5B cd09093
Catalytic inositol polyphosphate 5-phosphatase (INPP5c) domain of Type II inositol ...
 72-365 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: 579.65  E-value: 0e+00
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767904159  72 FRFFAGTYNVNGQSPKECLRLWLSNGIQAPDVYCVGFQELDLSKEAFFFHDTPKEEEWFKAVSEGLHPDAKYAKVKLIRL 151
Cdd:cd09093    1 FRIFVGTWNVNGQSPDESLRPWLSCDEEPPDIYAIGFQELDLSAEAFLFNDSSREQEWVKAVERGLHPDAKYKKVKLIRL 80

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767904159 152 VGIMLLLYVKQEHAAYISEVEAETVGTGIMGRMGNKGGVAIRFQFHNTSICVVNSHLAAHIEEYERRNQDYKDICSRMQF 231
Cdd:cd09093   81 VGMMLLVFVKKEHRQHIKEVAAETVGTGIMGKMGNKGGVAVRFQFHNTTFCFVNSHLAAHMEEVERRNQDYKDICARMKF 160

                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767904159 232 CQPDPslPPLTISNHDVILWLGDLNYRIEELDVEKVKKLIEEKDFQMLYAYDQLKIQVAAKTVFEGFTEGELTFQPTYKY 311
Cdd:cd09093  161 EDPDG--PPLSISDHDVVFWLGDLNYRIQELPTEEVKELIEKNDLEELLKYDQLNIQRRAGKVFEGFTEGEINFIPTYKY 238

                        250       260       270       280       290
                 ....*....|....*....|....*....|....*....|....*....|....
gi 767904159 312 DTGSDDWDTSEKCRAPAWCDRILWKGKNITQLSYQSHMALKTSDHKPVSSVFDI 365
Cdd:cd09093  239 DPGTDNWDSSEKCRAPAWCDRILWRGTNIVQLSYRSHMELKTSDHKPVSALFDI 292
IPPc smart00128
Inositol polyphosphate phosphatase, catalytic domain homologues; Mg(2+)-dependent/Li(+) ...
 70-367 6.53e-110

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


Pssm-ID: 214525 [Multi-domain]  Cd Length: 306  Bit Score: 335.48  E-value: 6.53e-110
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767904159    70 QNFRFFAGTYNVNGQS-PKECLRLWLSNGIQA-----PDVYCVGFQELDLSKE-AFFFHDTPKEEEWFKAVSEGLHPDAK 142
Cdd:smart00128   1 RDIKVLIGTWNVGGLEsPKVDVTSWLFQKIEVkqsekPDIYVIGLQEVVGLAPgVILETIAGKERLWSDLLESSLNGDGQ 80

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767904159   143 YAKVKLIRLVGIMLLLYVKQEHAAYISEVEAETVGTGIMGRMGNKGGVAIRFQFHNTSICVVNSHLAAHIEEYERRNQDY 222
Cdd:smart00128  81 YNVLAKVYLVGILVLVFVKANHLVYIKDVETFTVKTGMGGLWGNKGAVAVRFKLSDTSFCFVNSHLAAGASNVEQRNQDY 160

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767904159   223 KDICSRMQFcqpdPSLPPLTISNHDVILWLGDLNYRIEELDVEKVKKLIEEKDFQMLYAYDQLKIQVAAKTVFEGFTEGE 302
Cdd:smart00128 161 KTILRALSF----PERALLSQFDHDVVFWFGDLNFRLDSPSYEEVRRKISKKEFDDLLEKDQLNRQREAGKVFKGFQEGP 236

                          250       260       270       280       290       300
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 767904159   303 LTFQPTYKYDT-GSDDWDTSEKCRAPAWCDRILWK--GKNITQLS-YQSHMALKTSDHKPVSSVFDIGV 367
Cdd:smart00128 237 ITFPPTYKYDSvGTETYDTSEKKRVPAWCDRILYRsnGPELIQLSeYHSGMEITTSDHKPVFATFRLKV 305
RhoGAP_OCRL1 cd04380
RhoGAP_OCRL1: RhoGAP (GTPase-activator protein [GAP] for Rho-like small GTPases) domain ...
 499-719 1.90e-87

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: 273.83  E-value: 1.90e-87
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767904159 499 FLSVSGNYLPSCFGSPIHTLCYMREPILDLPLETIseltlmpvWTGDDGSQLDSPMEIPKELWMMVDYLYRNAVQQEDLF 578
Cdd:cd04380    1 FITVTGVYLPSCFGSSLETLIRLPDPGIRNLIDQL--------ELGDNPDYSEVPLSIPKEIWRLVDYLYTRGLAQEGLF 72

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767904159 579 QQPGLRSE----FEHIRDCLDTGMIDNLSASNHSVAEALLLFLESLPEPVICYSTYHNCLEC-SGNYTASKQVIS-TLPI 652
Cdd:cd04380   73 EEPGLPSEpgelLAEIRDALDTGSPFNSPGSAESVAEALLLFLESLPDPIIPYSLYERLLEAvANNEEDKRQVIRiSLPP 152

                        170       180       190       200       210       220
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 767904159 653 FHKNVFHYLMAFLRELLKNSAKNHLDENILASIFGSLLLRNPAGHQ-KLDMTEKKKAQEFIHQFLCNP 719
Cdd:cd04380  153 VHRNVFVYLCSFLRELLSESADRGLDENTLATIFGRVLLRDPPRAGgKERRAERDRKRAFIEQFLLND 220
COG5411 COG5411
Phosphatidylinositol 5-phosphate phosphatase [Signal transduction mechanisms];
59-373 1.17e-72

Phosphatidylinositol 5-phosphate phosphatase [Signal transduction mechanisms];


Pssm-ID: 227698 [Multi-domain]  Cd Length: 460  Bit Score: 243.15  E-value: 1.17e-72
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767904159  59 LLQKEEDYTYIQNFRFFAGTYNVNGQSPKECLRLWLSNGIQA---PDVYCVGFQE-LDLSKEAFFFHDT-PKEEEWF-KA 132
Cdd:COG5411   17 LRQRRSKYVIEKDVSIFVSTFNPPGKPPKASTKRWLFPEIEAtelADLYVVGLQEvVELTPGSILSADPyDRLRIWEsKV 96

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767904159 133 VSE--GLHPDAKYAKVKLIRLVGIMLLLYVKQEHAAYISEVEAETVGTGIMGRMGNKGGVAIRFQFHNTSICVVNSHLAA 210
Cdd:COG5411   97 LDClnGAQSDEKYSLLRSPQLGGILLRVFSLATNLPVVKPVSGTVKKTGFGGSSSNKGAVAIRFNYERTSFCFVNSHLAA 176

                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767904159 211 HIEEYERRNQDYKDICSRMQFCQPdpslppLTISNHDVILWLGDLNYRIEeLDVEKVKKLIEEKD--FQMLYAYDQLKIQ 288
Cdd:COG5411  177 GVNNIEERIFDYRSIASNICFSRG------LRIYDHDTIFWLGDLNYRVT-STNEEVRPEIASDDgrLDKLFEYDQLLWE 249

                        250       260       270       280       290       300       310       320
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767904159 289 VAAKTVFEGFTEGELTFQPTYKYDTGSDDWDTSEKCRAPAWCDRILWKGKNITQLSYQSHMALKTSDHKPVSSVFDIGVR 368
Cdd:COG5411  250 MEVGNVFPGFKEPVITFPPTYKFDYGTDEYDTSDKGRIPSWTDRILYKSEQLTPHSYSSIPHLMISDHRPVYATFRAKIK 329


                 ....*
gi 767904159 369 VVNDE 373
Cdd:COG5411  330 VVDPS 334
PLN03191 PLN03191
Type I inositol-1,4,5-trisphosphate 5-phosphatase 2; Provisional
 120-379 2.90e-57

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


Pssm-ID: 215624 [Multi-domain]  Cd Length: 621  Bit Score: 205.53  E-value: 2.90e-57
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767904159 120 FHDTPKEEEWFKAVSEGLHPDAKYAKVKLIRLVGIMLLLYVKQEHAAYISEVEAETVGTGIMGRMGNKGGVAIRFQFHNT 199
Cdd:PLN03191 341 FKEVPSYQLPEDLIKDCRKVKQKYVRIVSKQMVGIYVSVWVRKRLRRHINNLKVSPVGVGLMGYMGNKGSVSISMSLFQS 420

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767904159 200 SICVVNSHLAAHIEE--YERRNQDYKDICSRMQFCQPDPSLPPLTISNHDVILWLGDLNYRIEELDVEkVKKLIEEKDFQ 277
Cdd:PLN03191 421 RLCFVCSHLTSGHKDgaEQRRNADVYEIIRRTRFSSVLDTDQPQTIPSHDQIFWFGDLNYRLNMLDTE-VRKLVAQKRWD 499

                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767904159 278 MLYAYDQLKIQVAAKTVFEGFTEGELTFQPTYKYDTGSDDW-----DTSEKCRAPAWCDRILWKGKNITQLSYQsHMALK 352
Cdd:PLN03191 500 ELINSDQLIKELRSGHVFDGWKEGPIKFPPTYKYEINSDRYvgenpKEGEKKRSPAWCDRILWLGKGIKQLCYK-RSEIR 578

                        250       260
                 ....*....|....*....|....*..
gi 767904159 353 TSDHKPVSSVFDIGVRVVNDELYRKTL 379
Cdd:PLN03191 579 LSDHRPVSSMFLVEVEVFDHRKLQRAL 605
RhoGAP smart00324
GTPase-activator protein for Rho-like GTPases; GTPase activator proteins towards Rho/Rac ...
 555-719 1.16e-40

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: 146.64  E-value: 1.16e-40
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767904159   555 EIPKELWMMVDYLYRNAVQQEDLFQQPGLRSEFEHIRDCLDTGMIDNL---SASNHSVAEALLLFLESLPEPVICYSTYH 631
Cdd:smart00324   2 PIPIIVEKCIEYLEKRGLDTEGIYRVSGSKSRVKELRDAFDSGPDPDLdlsEYDVHDVAGLLKLFLRELPEPLITYELYE 81

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767904159   632 NCLECSGN------YTASKQVISTLPIFHKNVFHYLMAFLRELLKNSAKNHLDENILASIFGSLLLRNPAGHQKlDMTEK 705
Cdd:smart00324  82 EFIEAAKLedeterLRALRELLSLLPPANRATLRYLLAHLNRVAEHSEENKMTARNLAIVFGPTLLRPPDGEVA-SLKDI 160

                          170
                   ....*....|....
gi 767904159   706 KKAQEFIHQFLCNP 719
Cdd:smart00324 161 RHQNTVIEFLIENA 174
RhoGAP pfam00620
RhoGAP domain; GTPase activator proteins towards Rho/Rac/Cdc42-like small GTPases.
 557-695 9.19e-34

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


Pssm-ID: 459875  Cd Length: 148  Bit Score: 126.12  E-value: 9.19e-34
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767904159  557 PKELWMMVDYLYRNAVQQEDLFQQPGLRSEFEHIRDCLDTG---MIDNLSASNHSVAEALLLFLESLPEPVICYSTYHNC 633
Cdd:pfam00620   1 PLIVRKCVEYLEKRGLDTEGIFRVSGSASRIKELREAFDRGpdvDLDLEEEDVHVVASLLKLFLRELPEPLLTFELYEEF 80

                          90       100       110       120       130       140
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 767904159  634 LEC------SGNYTASKQVISTLPIFHKNVFHYLMAFLRELLKNSAKNHLDENILASIFGSLLLRNPA 695
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 ...
 72-365 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: 579.65  E-value: 0e+00
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767904159  72 FRFFAGTYNVNGQSPKECLRLWLSNGIQAPDVYCVGFQELDLSKEAFFFHDTPKEEEWFKAVSEGLHPDAKYAKVKLIRL 151
Cdd:cd09093    1 FRIFVGTWNVNGQSPDESLRPWLSCDEEPPDIYAIGFQELDLSAEAFLFNDSSREQEWVKAVERGLHPDAKYKKVKLIRL 80

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767904159 152 VGIMLLLYVKQEHAAYISEVEAETVGTGIMGRMGNKGGVAIRFQFHNTSICVVNSHLAAHIEEYERRNQDYKDICSRMQF 231
Cdd:cd09093   81 VGMMLLVFVKKEHRQHIKEVAAETVGTGIMGKMGNKGGVAVRFQFHNTTFCFVNSHLAAHMEEVERRNQDYKDICARMKF 160

                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767904159 232 CQPDPslPPLTISNHDVILWLGDLNYRIEELDVEKVKKLIEEKDFQMLYAYDQLKIQVAAKTVFEGFTEGELTFQPTYKY 311
Cdd:cd09093  161 EDPDG--PPLSISDHDVVFWLGDLNYRIQELPTEEVKELIEKNDLEELLKYDQLNIQRRAGKVFEGFTEGEINFIPTYKY 238

                        250       260       270       280       290
                 ....*....|....*....|....*....|....*....|....*....|....
gi 767904159 312 DTGSDDWDTSEKCRAPAWCDRILWKGKNITQLSYQSHMALKTSDHKPVSSVFDI 365
Cdd:cd09093  239 DPGTDNWDSSEKCRAPAWCDRILWRGTNIVQLSYRSHMELKTSDHKPVSALFDI 292
INPP5c cd09074
Catalytic domain of inositol polyphosphate 5-phosphatases; Inositol polyphosphate ...
 72-365 3.46e-141

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: 415.58  E-value: 3.46e-141
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767904159  72 FRFFAGTYNVNGQ-SPKECLRLWLS-NGIQAPDVYCVGFQELDLSKEAFF-FHDTPKEEEWFKAVSEGLHPDAKYAKVKL 148
Cdd:cd09074    1 VKIFVVTWNVGGGiSPPENLENWLSpKGTEAPDIYAVGVQEVDMSVQGFVgNDDSAKAREWVDNIQEALNEKENYVLLGS 80

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767904159 149 IRLVGIMLLLYVKQEHAAYIS--EVEAETVGTGIMGRMGNKGGVAIRFQFHNTSICVVNSHLAAHIEEYERRNQDYKDIC 226
Cdd:cd09074   81 AQLVGIFLFVFVKKEHLPQIKdlEVEGVTVGTGGGGKLGNKGGVAIRFQINDTSFCFVNSHLAAGQEEVERRNQDYRDIL 160

                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767904159 227 SRMQFCQPDPslPPLTISNHDVILWLGDLNYRIEELDVEkVKKLIEEKDFQMLYAYDQLKIQVAAKTVFEGFTEGELTFQ 306
Cdd:cd09074  161 SKLKFYRGDP--AIDSIFDHDVVFWFGDLNYRIDSTDDE-VRKLISQGDLDDLLEKDQLKKQKEKGKVFDGFQELPITFP 237

                        250       260       270       280       290       300
                 ....*....|....*....|....*....|....*....|....*....|....*....|..
gi 767904159 307 PTYKYDTGSDDWDTSEKCRAPAWCDRILWK---GKNITQLSYQSHMALKTSDHKPVSSVFDI 365
Cdd:cd09074  238 PTYKFDPGTDEYDTSDKKRIPAWCDRILYKskaGSEIQPLSYTSVPLYKTSDHKPVRATFRV 299
IPPc smart00128
Inositol polyphosphate phosphatase, catalytic domain homologues; Mg(2+)-dependent/Li(+) ...
 70-367 6.53e-110

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


Pssm-ID: 214525 [Multi-domain]  Cd Length: 306  Bit Score: 335.48  E-value: 6.53e-110
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767904159    70 QNFRFFAGTYNVNGQS-PKECLRLWLSNGIQA-----PDVYCVGFQELDLSKE-AFFFHDTPKEEEWFKAVSEGLHPDAK 142
Cdd:smart00128   1 RDIKVLIGTWNVGGLEsPKVDVTSWLFQKIEVkqsekPDIYVIGLQEVVGLAPgVILETIAGKERLWSDLLESSLNGDGQ 80

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767904159   143 YAKVKLIRLVGIMLLLYVKQEHAAYISEVEAETVGTGIMGRMGNKGGVAIRFQFHNTSICVVNSHLAAHIEEYERRNQDY 222
Cdd:smart00128  81 YNVLAKVYLVGILVLVFVKANHLVYIKDVETFTVKTGMGGLWGNKGAVAVRFKLSDTSFCFVNSHLAAGASNVEQRNQDY 160

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767904159   223 KDICSRMQFcqpdPSLPPLTISNHDVILWLGDLNYRIEELDVEKVKKLIEEKDFQMLYAYDQLKIQVAAKTVFEGFTEGE 302
Cdd:smart00128 161 KTILRALSF----PERALLSQFDHDVVFWFGDLNFRLDSPSYEEVRRKISKKEFDDLLEKDQLNRQREAGKVFKGFQEGP 236

                          250       260       270       280       290       300
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 767904159   303 LTFQPTYKYDT-GSDDWDTSEKCRAPAWCDRILWK--GKNITQLS-YQSHMALKTSDHKPVSSVFDIGV 367
Cdd:smart00128 237 ITFPPTYKYDSvGTETYDTSEKKRVPAWCDRILYRsnGPELIQLSeYHSGMEITTSDHKPVFATFRLKV 305
INPP5c_ScInp51p-like cd09090
Catalytic inositol polyphosphate 5-phosphatase (INPP5c) domain of Saccharomyces cerevisiae ...
 73-363 3.54e-98

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: 304.65  E-value: 3.54e-98
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767904159  73 RFFAGTYNVNGQSPKECLRLWL--SNGIQAPDVYCVGFQEL-DLSKEAFFFHDTPKEEEWFKAVSEGL--HPDAKYAKVK 147
Cdd:cd09090    2 NIFVGTFNVNGKSYKDDLSSWLfpEENDELPDIVVIGLQEVvELTAGQILNSDPSKSSFWEKKIKTTLngRGGEKYVLLR 81

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767904159 148 LIRLVGIMLLLYVKQEHAAYISEVEAETVGTGIMGRMGNKGGVAIRFQFHNTSICVVNSHLAAHIEEYERRNQDYKDICS 227
Cdd:cd09090   82 SEQLVGTALLFFVKESQLPKVKNVEGSTKKTGLGGMSGNKGAVAIRFDYGDTSFCFVTSHLAAGLTNYEERNNDYKTIAR 161

                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767904159 228 RMQFCQPdpslppLTISNHDVILWLGDLNYRIEeLDVEKVKKLIEEKDFQMLYAYDQLKIQVAAKTVFEGFTEGELTFQP 307
Cdd:cd09090  162 GLRFSRG------RTIKDHDHVIWLGDFNYRIS-LTNEDVRRFILNGKLDKLLEYDQLNQQMNAGEVFPGFSEGPITFPP 234

                        250       260       270       280       290
                 ....*....|....*....|....*....|....*....|....*....|....*.
gi 767904159 308 TYKYDTGSDDWDTSEKCRAPAWCDRILWKGKNITQLSYQSHMaLKTSDHKPVSSVF 363
Cdd:cd09090  235 TYKYDKGTDNYDTSEKQRIPAWTDRILYRGENLRQLSYNSAP-LRFSDHRPVYATF 289
INPP5c_INPP5J-like cd09094
Catalytic inositol polyphosphate 5-phosphatase (INPP5c) domain of inositol polyphosphate ...
 72-365 6.20e-93

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: 291.20  E-value: 6.20e-93
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767904159  72 FRFFAGTYNVNGQSPKECLR---LWLSNGiQAPDVYCVGFQELDlSKEAFFFHDTPKEEEWFKAVSEGLHPDaKYAKVKL 148
Cdd:cd09094    1 LRVYVVTWNVATAPPPIDVRsllGLQSPE-VAPDIYIIGLQEVN-SKPVQFVSDLIFDDPWSDLFMDILSPK-GYVKVSS 77

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767904159 149 IRLVGIMLLLYVKQEHAAYISEVEAETVGTGIMGRMGNKGGVAIRFQFHNTSICVVNSHLAAHIEEYERRNQDYKDICSR 228
Cdd:cd09094   78 IRLQGLLLLVFVKIQHLPFIRDVQTNYTRTGLGGYWGNKGAVTVRFSLYGHMICFLNCHLPAHMEKWEQRIDDFETILST 157

                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767904159 229 MQFCQPDPSlpplTISNHDVILWLGDLNYRIEELDVEKVKKLIEEKDFQMLYAYDQLKIQVAAKTVFEGFTEGELTFQPT 308
Cdd:cd09094  158 QVFNECNTP----SILDHDYVFWFGDLNFRIEDVSIEFVRELVNSKKYHLLLEKDQLNMAKRKEEAFQGFQEGPLNFAPT 233

                        250       260       270       280       290       300
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 767904159 309 YKYDTGSDDWDTSEKCRAPAWCDRILWKGK----------NITQLSYQSHMALKTSDHKPVSSVFDI 365
Cdd:cd09094  234 YKFDLGTDEYDTSGKKRKPAWTDRILWKVNpdasteekflSITQTSYKSHMEYGISDHKPVTAQFRL 300
INPP5c_Synj cd09089
Catalytic inositol polyphosphate 5-phosphatase (INPP5c) domain of synaptojanins; This ...
 73-365 7.10e-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: 281.59  E-value: 7.10e-89
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767904159  73 RFFAGTYNVNGQS-------PKECLRLWLSNGIQA--------------PDVYCVGFQEL-DLSKEAFFFHDTPKEEEWF 130
Cdd:cd09089    2 RVFVGTWNVNGGKhfrsiafKHQSMTDWLLDNPKLagqcsndseedekpVDIFAIGFEEMvDLNASNIVSASTTNQKEWG 81

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767904159 131 KAVSEGLHPDAKYAKVKLIRLVGIMLLLYVKQEHAAYISEVEAETVGTGIMGRMGNKGGVAIRFQFHNTSICVVNSHLAA 210
Cdd:cd09089   82 EELQKTISRDHKYVLLTSEQLVGVCLFVFVRPQHAPFIRDVAVDTVKTGLGGAAGNKGAVAIRFLLHSTSLCFVCSHFAA 161

                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767904159 211 HIEEYERRNQDYKDICSRMQFcqpdpslpPL--TISNHDVILWLGDLNYRIEeLDVEKVKKLIEEKDFQMLYAYDQLKIQ 288
Cdd:cd09089  162 GQSQVKERNEDFAEIARKLSF--------PMgrTLDSHDYVFWCGDFNYRID-LPNDEVKELVRNGDWLKLLEFDQLTKQ 232

                        250       260       270       280       290       300       310       320
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767904159 289 VAAKTVFEGFTEGELTFQPTYKYDTGSDDWDTSEKCRAPAWCDRILWKGK-------------------NITQLSYQSHM 349
Cdd:cd09089  233 KAAGNVFKGFLEGEINFAPTYKYDLFSDDYDTSEKCRTPAWTDRVLWRRRkwpsdkteeslvetndptwNPGTLLYYGRA 312

                        330
                 ....*....|....*.
gi 767904159 350 ALKTSDHKPVSSVFDI 365
Cdd:cd09089  313 ELKTSDHRPVVAIIDI 328
RhoGAP_OCRL1 cd04380
RhoGAP_OCRL1: RhoGAP (GTPase-activator protein [GAP] for Rho-like small GTPases) domain ...
 499-719 1.90e-87

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: 273.83  E-value: 1.90e-87
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767904159 499 FLSVSGNYLPSCFGSPIHTLCYMREPILDLPLETIseltlmpvWTGDDGSQLDSPMEIPKELWMMVDYLYRNAVQQEDLF 578
Cdd:cd04380    1 FITVTGVYLPSCFGSSLETLIRLPDPGIRNLIDQL--------ELGDNPDYSEVPLSIPKEIWRLVDYLYTRGLAQEGLF 72

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767904159 579 QQPGLRSE----FEHIRDCLDTGMIDNLSASNHSVAEALLLFLESLPEPVICYSTYHNCLEC-SGNYTASKQVIS-TLPI 652
Cdd:cd04380   73 EEPGLPSEpgelLAEIRDALDTGSPFNSPGSAESVAEALLLFLESLPDPIIPYSLYERLLEAvANNEEDKRQVIRiSLPP 152

                        170       180       190       200       210       220
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 767904159 653 FHKNVFHYLMAFLRELLKNSAKNHLDENILASIFGSLLLRNPAGHQ-KLDMTEKKKAQEFIHQFLCNP 719
Cdd:cd04380  153 VHRNVFVYLCSFLRELLSESADRGLDENTLATIFGRVLLRDPPRAGgKERRAERDRKRAFIEQFLLND 220
COG5411 COG5411
Phosphatidylinositol 5-phosphate phosphatase [Signal transduction mechanisms];
59-373 1.17e-72

Phosphatidylinositol 5-phosphate phosphatase [Signal transduction mechanisms];


Pssm-ID: 227698 [Multi-domain]  Cd Length: 460  Bit Score: 243.15  E-value: 1.17e-72
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767904159  59 LLQKEEDYTYIQNFRFFAGTYNVNGQSPKECLRLWLSNGIQA---PDVYCVGFQE-LDLSKEAFFFHDT-PKEEEWF-KA 132
Cdd:COG5411   17 LRQRRSKYVIEKDVSIFVSTFNPPGKPPKASTKRWLFPEIEAtelADLYVVGLQEvVELTPGSILSADPyDRLRIWEsKV 96

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767904159 133 VSE--GLHPDAKYAKVKLIRLVGIMLLLYVKQEHAAYISEVEAETVGTGIMGRMGNKGGVAIRFQFHNTSICVVNSHLAA 210
Cdd:COG5411   97 LDClnGAQSDEKYSLLRSPQLGGILLRVFSLATNLPVVKPVSGTVKKTGFGGSSSNKGAVAIRFNYERTSFCFVNSHLAA 176

                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767904159 211 HIEEYERRNQDYKDICSRMQFCQPdpslppLTISNHDVILWLGDLNYRIEeLDVEKVKKLIEEKD--FQMLYAYDQLKIQ 288
Cdd:COG5411  177 GVNNIEERIFDYRSIASNICFSRG------LRIYDHDTIFWLGDLNYRVT-STNEEVRPEIASDDgrLDKLFEYDQLLWE 249

                        250       260       270       280       290       300       310       320
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767904159 289 VAAKTVFEGFTEGELTFQPTYKYDTGSDDWDTSEKCRAPAWCDRILWKGKNITQLSYQSHMALKTSDHKPVSSVFDIGVR 368
Cdd:COG5411  250 MEVGNVFPGFKEPVITFPPTYKFDYGTDEYDTSDKGRIPSWTDRILYKSEQLTPHSYSSIPHLMISDHRPVYATFRAKIK 329


                 ....*
gi 767904159 369 VVNDE 373
Cdd:COG5411  330 VVDPS 334
INPP5c_Synj1 cd09098
Catalytic inositol polyphosphate 5-phosphatase (INPP5c) domain of synaptojanin 1; This ...
 73-365 1.91e-68

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


Pssm-ID: 197332  Cd Length: 336  Bit Score: 228.00  E-value: 1.91e-68
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767904159  73 RFFAGTYNVNGQSP-------KECLRLWLsngIQAP----------------DVYCVGFQEL-DLSKEAFFFHDTPKEEE 128
Cdd:cd09098    2 RVCVGTWNVNGGKQfrsiafkNQTLTDWL---LDAPkkagipefqdvrskpvDIFAIGFEEMvELNAGNIVSASTTNQKL 78

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767904159 129 WFKAVSEGLHPDAKYAKVKLIRLVGIMLLLYVKQEHAAYISEVEAETVGTGIMGRMGNKGGVAIRFQFHNTSICVVNSHL 208
Cdd:cd09098   79 WAAELQKTISRDQKYVLLASEQLVGVCLFVFIRPQHAPFIRDVAVDTVKTGMGGATGNKGAVAIRMLFHTTSLCFVCSHF 158

                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767904159 209 AAHIEEYERRNQDYKDICSRMQFcqpdpslpPL--TISNHDVILWLGDLNYRIEeLDVEKVKKLIEEKDFQMLYAYDQLK 286
Cdd:cd09098  159 AAGQSQVKERNEDFIEIARKLSF--------PMgrMLFSHDYVFWCGDFNYRID-IPNEEVKELIRQQNWDSLIAGDQLI 229

                        250       260       270       280       290       300       310       320
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767904159 287 IQVAAKTVFEGFTEGELTFQPTYKYDTGSDDWDTSEKCRAPAWCDRILWKGK---------------------------- 338
Cdd:cd09098  230 NQKNAGQVFRGFLEGKLDFAPTYKYDLFSDDYDTSEKCRTPAWTDRVLWRRRkwpfdrsaedldllnasfpdnskeqytw 309

                        330       340
                 ....*....|....*....|....*..
gi 767904159 339 NITQLSYQSHMALKTSDHKPVSSVFDI 365
Cdd:cd09098  310 SPGTLLHYGRAELKTSDHRPVVALIDI 336
INPP5c_Synj2 cd09099
Catalytic inositol polyphosphate 5-phosphatase (INPP5c) domain of synaptojanin 2; This ...
 73-365 2.96e-65

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: 219.51  E-value: 2.96e-65
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767904159  73 RFFAGTYNVNGQ--------SPKEcLRLWL-------------SNGIQAPDVYCVGFQEL-DLSKEAFFFHDTPKEEEWF 130
Cdd:cd09099    2 RVAMGTWNVNGGkqfrsnilGTSE-LTDWLldspklsgtpdfqDDESNPPDIFAVGFEEMvELSAGNIVNASTTNRKMWG 80

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767904159 131 KAVSEGLHPDAKYAKVKLIRLVGIMLLLYVKQEHAAYISEVEAETVGTGIMGRMGNKGGVAIRFQFHNTSICVVNSHLAA 210
Cdd:cd09099   81 EQLQKAISRSHRYILLTSAQLVGVCLFIFVRPYHVPFIRDVAIDTVKTGMGGKAGNKGAVAIRFQFYSTSFCFICSHLTA 160

                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767904159 211 HIEEYERRNQDYKDICSRMQFcqpdpslpPL--TISNHDVILWLGDLNYRIeELDVEKVKKLIEEKDFQMLYAYDQLKIQ 288
Cdd:cd09099  161 GQNQVKERNEDYKEITQKLSF--------PMgrNVFSHDYVFWCGDFNYRI-DLTYEEVFYFIKRQDWKKLLEFDQLQLQ 231

                        250       260       270       280       290       300       310       320
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767904159 289 VAAKTVFEGFTEGELTFQPTYKYDTGSDDWDTSEKCRAPAWCDRILWKGK----------------------NITQ---- 342
Cdd:cd09099  232 KSSGKIFKDFHEGTINFGPTYKYDVGSEAYDTSDKCRTPAWTDRVLWWRKkwpfektageinlldsdldfdtKIRHtwtp 311

                        330       340
                 ....*....|....*....|....*
gi 767904159 343 --LSYQSHMALKTSDHKPVSSVFDI 365
Cdd:cd09099  312 gaLMYYGRAELQASDHRPVLAIVEV 336
PLN03191 PLN03191
Type I inositol-1,4,5-trisphosphate 5-phosphatase 2; Provisional
 120-379 2.90e-57

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


Pssm-ID: 215624 [Multi-domain]  Cd Length: 621  Bit Score: 205.53  E-value: 2.90e-57
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767904159 120 FHDTPKEEEWFKAVSEGLHPDAKYAKVKLIRLVGIMLLLYVKQEHAAYISEVEAETVGTGIMGRMGNKGGVAIRFQFHNT 199
Cdd:PLN03191 341 FKEVPSYQLPEDLIKDCRKVKQKYVRIVSKQMVGIYVSVWVRKRLRRHINNLKVSPVGVGLMGYMGNKGSVSISMSLFQS 420

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767904159 200 SICVVNSHLAAHIEE--YERRNQDYKDICSRMQFCQPDPSLPPLTISNHDVILWLGDLNYRIEELDVEkVKKLIEEKDFQ 277
Cdd:PLN03191 421 RLCFVCSHLTSGHKDgaEQRRNADVYEIIRRTRFSSVLDTDQPQTIPSHDQIFWFGDLNYRLNMLDTE-VRKLVAQKRWD 499

                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767904159 278 MLYAYDQLKIQVAAKTVFEGFTEGELTFQPTYKYDTGSDDW-----DTSEKCRAPAWCDRILWKGKNITQLSYQsHMALK 352
Cdd:PLN03191 500 ELINSDQLIKELRSGHVFDGWKEGPIKFPPTYKYEINSDRYvgenpKEGEKKRSPAWCDRILWLGKGIKQLCYK-RSEIR 578

                        250       260
                 ....*....|....*....|....*..
gi 767904159 353 TSDHKPVSSVFDIGVRVVNDELYRKTL 379
Cdd:PLN03191 579 LSDHRPVSSMFLVEVEVFDHRKLQRAL 605
INPP5c_INPP5E-like cd09095
Catalytic inositol polyphosphate 5-phosphatase (INPP5c) domain of Inositol ...
 70-365 3.50e-54

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: 188.40  E-value: 3.50e-54
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767904159  70 QNFRFFAGTYNVNGQS--PKECLRLWLSNGIQ-APDVYCVGFQEldlskeafffhDTPKEEEWFKAVSEGLHPdaKYAKV 146
Cdd:cd09095    3 RNVGIFVATWNMQGQKelPENLDDFLLPTSADfAQDIYVIGVQE-----------GCSDRREWEIRLQETLGP--SHVLL 69

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767904159 147 KLIRLVGIMLLLYVKQEHAAYISEVEAETVGTGIMGRMGNKGGVAIRFQFHNTSICVVNSHLAAHIEEYERRNQDYKDIC 226
Cdd:cd09095   70 HSASHGVLHLAVFIRRDLIWFCSEVESATVTTRIVSQIKTKGALAISFTFFGTSFLFITSHFTSGDGKVKERVLDYNKII 149

                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767904159 227 SRMQFCQPDPSLP-------PLTisNHDVILWLGDLNYRIEElDVEKVKKLIE---EKDFQMLYAYDQLKIQVAAKTVFE 296
Cdd:cd09095  150 QALNLPRNVPTNPyksesgdVTT--RFDEVFWFGDFNFRLSG-PRHLVDALINqgqEVDVSALLQHDQLTREMSKGSIFK 226

                        250       260       270       280       290       300       310
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|..
gi 767904159 297 GFTEGELTFQPTYKYDTGSDDWDTSEKCRAPAWCDRILWKGK---NITQLSYQSHMALKTSDHKPVSSVFDI 365
Cdd:cd09095  227 GFQEAPIHFPPTYKFDIGSDVYDTSSKQRVPSYTDRILYRSRqkgDVCCLKYNSCPSIKTSDHRPVFALFRV 298
INPP5c_SHIP2-INPPL1 cd09101
Catalytic inositol polyphosphate 5-phosphatase (INPP5c) domain of SH2 domain containing ...
 75-365 5.61e-50

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: 177.09  E-value: 5.61e-50
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767904159  75 FAGTYNVNGQSPKECLRLWL-SNGIQAP----------DVYCVGFQELDLSkeafffhdtpkEEEWFKAVSEGLHP--DA 141
Cdd:cd09101    4 FIGTWNMGSVPPPKSLASWLtSRGLGKTldettvtiphDIYVFGTQENSVG-----------DREWVDFLRASLKEltDI 72

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767904159 142 KYAKVKLIRLVGIMLLLYVKQEHAAYISEVEAETVGTGIMGRMGNKGGVAIRFQFHNTSICVVNSHLAAHIEEYERRNQD 221
Cdd:cd09101   73 DYQPIALQCLWNIKMVVLVKPEHENRISHVHTSSVKTGIANTLGNKGAVGVSFMFNGTSFGFVNCHLTSGNEKTHRRNQN 152

                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767904159 222 YKDICSRMQFcqPDPSLPPLTIS---NHdvILWLGDLNYRIeELDVEKVKKLIEEKDFQMLYAYDQLKIQVAAKTVFEGF 298
Cdd:cd09101  153 YLDILRSLSL--GDKQLNAFDISlrfTH--LFWFGDLNYRL-DMDIQEILNYITRKEFDPLLAVDQLNLEREKNKVFLRF 227

                        250       260       270       280       290       300       310
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 767904159 299 TEGELTFQPTYKYDTGSDD---WD----TSEKCRAPAWCDRILWKGKNITQL---SYQSHMALKTSDHKPVSSVFDI 365
Cdd:cd09101  228 REEEISFPPTYRYERGSRDtymWQkqktTGMRTNVPSWCDRILWKSYPETHIvcnSYGCTDDIVTSDHSPVFGTFEV 304
INPP5c_SHIP cd09091
Catalytic inositol polyphosphate 5-phosphatase (INPP5c) domain of SH2 domain containing ...
 75-365 1.73e-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: 175.90  E-value: 1.73e-49
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767904159  75 FAGTYNVNGQSPKECLRLWLSNGIQAP-----------DVYCVGFQEldlskeafffhDTPKEEEWFKAVSEGLH--PDA 141
Cdd:cd09091    4 FIGTWNMGSAPPPKNITSWFTSKGQGKtrddvadyiphDIYVIGTQE-----------DPLGEKEWLDLLRHSLKelTSL 72

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767904159 142 KYAKVKLIRLVGIMLLLYVKQEHAAYISEVEAETVGTGIMGRMGNKGGVAIRFQFHNTSICVVNSHLAAHIEEYERRNQD 221
Cdd:cd09091   73 DYKPIAMQTLWNIRIVVLAKPEHENRISHVCTSSVKTGIANTLGNKGAVGVSFMFNGTSFGFVNSHLTSGSEKKLRRNQN 152

                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767904159 222 YKDICSRMQFcqPDPSLPPLTIS---NHdvILWLGDLNYRIE--ELDVEKVKKLIEEKDFQMLYAYDQLKIQVAAKTVFE 296
Cdd:cd09091  153 YLNILRFLSL--GDKKLSAFNIThrfTH--LFWLGDLNYRLDlpIQEAENIIQKIEQQQFEPLLRHDQLNLEREEHKVFL 228

                        250       260       270       280       290       300       310
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 767904159 297 GFTEGELTFQPTYKYDTGSDD---WD----TSEKCRAPAWCDRILWKGKNITQL---SYQSHMALKTSDHKPVSSVFDI 365
Cdd:cd09091  229 RFSEEEITFPPTYRYERGSRDtyaYTkqkaTGVKYNLPSWCDRILWKSYPETHIicqSYGCTDDIVTSDHSPVFGTFEV 307
INPP5c_SHIP1-INPP5D cd09100
Catalytic inositol polyphosphate 5-phosphatase (INPP5c) domain of SH2 domain containing ...
 75-365 1.15e-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: 173.63  E-value: 1.15e-48
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767904159  75 FAGTYNVNGQSPKECLRLWLSNGIQAP-----------DVYCVGFQEldlskeafffhDTPKEEEWFKAVSEGLH--PDA 141
Cdd:cd09100    4 FIGTWNMGNAPPPKKITSWFQCKGQGKtrddtadyiphDIYVIGTQE-----------DPLGEKEWLDTLKHSLReiTSI 72

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767904159 142 KYAKVKLIRLVGIMLLLYVKQEHAAYISEVEAETVGTGIMGRMGNKGGVAIRFQFHNTSICVVNSHLAAHIEEYERRNQD 221
Cdd:cd09100   73 SFKVIAIQTLWNIRIVVLAKPEHENRISHICTDSVKTGIANTLGNKGAVGVSFMFNGTSFGFVNSHLTSGSEKKLRRNQN 152

                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767904159 222 YKDICSRMQFcqPDPSLPPLTIS---NHdvILWLGDLNYRIE--ELDVEKVKKLIEEKDFQMLYAYDQLKIQVAAKTVFE 296
Cdd:cd09100  153 YFNILRFLVL--GDKKLSPFNIThrfTH--LFWLGDLNYRVElpNTEAENIIQKIKQQQYQELLPHDQLLIERKESKVFL 228

                        250       260       270       280       290       300       310
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 767904159 297 GFTEGELTFQPTYKYDTGSDDWDTSEKCRA-------PAWCDRILWKGKNITQL---SYQSHMALKTSDHKPVSSVFDI 365
Cdd:cd09100  229 QFEEEEITFAPTYRFERGTRERYAYTKQKAtgmkynlPSWCDRVLWKSYPLVHVvcqSYGCTDDITTSDHSPVFATFEV 307
RhoGAP smart00324
GTPase-activator protein for Rho-like GTPases; GTPase activator proteins towards Rho/Rac ...
 555-719 1.16e-40

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: 146.64  E-value: 1.16e-40
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767904159   555 EIPKELWMMVDYLYRNAVQQEDLFQQPGLRSEFEHIRDCLDTGMIDNL---SASNHSVAEALLLFLESLPEPVICYSTYH 631
Cdd:smart00324   2 PIPIIVEKCIEYLEKRGLDTEGIYRVSGSKSRVKELRDAFDSGPDPDLdlsEYDVHDVAGLLKLFLRELPEPLITYELYE 81

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767904159   632 NCLECSGN------YTASKQVISTLPIFHKNVFHYLMAFLRELLKNSAKNHLDENILASIFGSLLLRNPAGHQKlDMTEK 705
Cdd:smart00324  82 EFIEAAKLedeterLRALRELLSLLPPANRATLRYLLAHLNRVAEHSEENKMTARNLAIVFGPTLLRPPDGEVA-SLKDI 160

                          170
                   ....*....|....
gi 767904159   706 KKAQEFIHQFLCNP 719
Cdd:smart00324 161 RHQNTVIEFLIENA 174
RhoGAP pfam00620
RhoGAP domain; GTPase activator proteins towards Rho/Rac/Cdc42-like small GTPases.
 557-695 9.19e-34

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


Pssm-ID: 459875  Cd Length: 148  Bit Score: 126.12  E-value: 9.19e-34
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767904159  557 PKELWMMVDYLYRNAVQQEDLFQQPGLRSEFEHIRDCLDTG---MIDNLSASNHSVAEALLLFLESLPEPVICYSTYHNC 633
Cdd:pfam00620   1 PLIVRKCVEYLEKRGLDTEGIFRVSGSASRIKELREAFDRGpdvDLDLEEEDVHVVASLLKLFLRELPEPLLTFELYEEF 80

                          90       100       110       120       130       140
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 767904159  634 LEC------SGNYTASKQVISTLPIFHKNVFHYLMAFLRELLKNSAKNHLDENILASIFGSLLLRNPA 695
Cdd:pfam00620  81 IEAaklpdeEERLEALRELLRKLPPANRDTLRYLLAHLNRVAQNSDVNKMNAHNLAIVFGPTLLRPPD 148
RhoGAP cd00159
RhoGAP: GTPase-activator protein (GAP) for Rho-like GTPases; GAPs towards Rho/Rac/Cdc42-like ...
 557-718 6.03e-27

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: 107.77  E-value: 6.03e-27
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767904159 557 PKELWMMVDYLYRNAVQQEDLFQQPGLRSEFEHIRDCLDTGM-IDNLSASN-HSVAEALLLFLESLPEPVICYSTYHNCL 634
Cdd:cd00159    1 PLIIEKCIEYLEKNGLNTEGIFRVSGSASKIEELKKKFDRGEdIDDLEDYDvHDVASLLKLYLRELPEPLIPFELYDEFI 80

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767904159 635 ECSGNYTAS------KQVISTLPIFHKNVFHYLMAFLRELLKNSAKNHLDENILASIFGSLLLRNPAGHQKlDMTEKKKA 708
Cdd:cd00159   81 ELAKIEDEEeriealKELLKSLPPENRDLLKYLLKLLHKISQNSEVNKMTASNLAIVFAPTLLRPPDSDDE-LLEDIKKL 159

                        170
                 ....*....|
gi 767904159 709 QEFIHQFLCN 718
Cdd:cd00159  160 NEIVEFLIEN 169
RhoGAP_FAM13A1a cd04393
RhoGAP_FAM13A1a: RhoGAP (GTPase-activator protein [GAP] for Rho-like small GTPases) domain of ...
 555-687 1.24e-16

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: 78.66  E-value: 1.24e-16
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767904159 555 EIPKELWMMVDYLYRNAVQQEDLFQQPGLRSEFEHIRDCLDTGMIDNLS--ASNHSVAEALLLFLESLPEPVICYSTYHN 632
Cdd:cd04393   19 GVPAVVRHIVEYLEQHGLEQEGLFRVNGNAETVEWLRQRLDSGEEVDLSkeADVCSAASLLRLFLQELPEGLIPASLQIR 98

                         90       100       110       120       130       140
                 ....*....|....*....|....*....|....*....|....*....|....*....|..
gi 767904159 633 CLECSGNYTAS-------KQVISTLPIFHKNVFHYLMAFLRELLKNSAKNHLDENILASIFG 687
Cdd:cd04393   99 LMQLYQDYNGEdefgrklRDLLQQLPPVNYSLLKFLCHFLSNVASQHHENRMTAENLAAVFG 160
RhoGAP_ARHGAP22_24_25 cd04390
RhoGAP_ARHGAP22_24_25: GTPase-activator protein (GAP) domain for Rho-like GTPases found in ...
 564-692 2.63e-13

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: 69.39  E-value: 2.63e-13
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767904159 564 VDYLYRNAVQQEDLFQQPGLRSEFEHIRDCLDTGMIDNLSASN--HSVAEALLLFLESLPEPVICYSTYHNCLECSGNYT 641
Cdd:cd04390   30 VDFIREHGLKEEGLFRLPGQANLVKQLQDAFDAGERPSFDSDTdvHTVASLLKLYLRELPEPVIPWAQYEDFLSCAQLLS 109

                         90       100       110       120       130
                 ....*....|....*....|....*....|....*....|....*....|....*....
gi 767904159 642 AS--------KQVISTLPIFHKNVFHYLMAFLRELLKNSAKNHLDENILASIFGSLLLR 692
Cdd:cd04390  110 KDeekglgelMKQVSILPKVNYNLLSYICRFLDEVQSNSSVNKMSVQNLATVFGPNILR 168
RhoGAP_KIAA1688 cd04389
RhoGAP_KIAA1688: GTPase-activator protein (GAP) domain for Rho-like GTPases found in ...
 573-718 2.14e-12

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


Pssm-ID: 239854  Cd Length: 187  Bit Score: 66.26  E-value: 2.14e-12
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767904159 573 QQEDLFQQPGLRSEFEHIRDCLDTGMIDNLSASN-HSVAEALLLFLESLPEPVICYSTYHNCLECSGNYTASKQVISTLP 651
Cdd:cd04389   39 QTEGIFRVPGDIDEVNELKLRVDQWDYPLSGLEDpHVPASLLKLWLRELEEPLIPDALYQQCISASEDPDKAVEIVQKLP 118

                         90       100       110       120       130       140
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 767904159 652 IFHKNVFHYLMAFLRELLK--NSAKNHLDENILASIFGSLLLRNPAGHQKLDMTEKKKAQEFIHQFLCN 718
Cdd:cd04389  119 IINRLVLCYLINFLQVFAQpeNVAHTKMDVSNLAMVFAPNILRCTSDDPRVIFENTRKEMSFLRTLIEH 187
RhoGAP_srGAP cd04383
RhoGAP_srGAP: RhoGAP (GTPase-activator protein [GAP] for Rho-like small GTPases) domain ...
 551-697 1.24e-11

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: 63.98  E-value: 1.24e-11
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767904159 551 DSPMEIPKELWMMVDYLYRNAVQQEDLFQQPGLRSEFEHIRDCLDTG---MIDNLSASN-HSVAEALLLFLESLPEPVIC 626
Cdd:cd04383   13 DSGQAIPLVVESCIRFINLYGLQHQGIFRVSGSQVEVNDIKNAFERGedpLADDQNDHDiNSVAGVLKLYFRGLENPLFP 92

                         90       100       110       120       130       140       150
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 767904159 627 YSTYHNCLEC------SGNYTASKQVISTLPIFHKNVFHYLMAFLRELLKNSAKNHLDENILASIFGSLLLRNPAGH 697
Cdd:cd04383   93 KERFEDLMSCvklenpTERVHQIREILSTLPRSVIIVMRYLFAFLNHLSQFSDENMMDPYNLAICFGPTLMPVPEGQ 169
EEP cd08372
Exonuclease-Endonuclease-Phosphatase (EEP) domain superfamily; This large superfamily includes ...
 77-359 1.68e-11

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: 64.81  E-value: 1.68e-11
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767904159  77 GTYNVNGQSPKECLRLWLSNgIQAPDVYCVGFQELDLSKEAFFFHDTPKEEEWFKAVSEGLHPDaKYAKVklirlvgiml 156
Cdd:cd08372    2 ASYNVNGLNAATRASGIARW-VRELDPDIVCLQEVKDSQYSAVALNQLLPEGYHQYQSGPSRKE-GYEGV---------- 69

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767904159 157 LLYVKQEHAAyISEVeaeTVGTGIMGRMGNKGGVAIRFQFHNTSICVVNSHLAAHIEEYERRNQDYKDICSRMQFcqpdp 236
Cdd:cd08372   70 AILSKTPKFK-IVEK---HQYKFGEGDSGERRAVVVKFDVHDKELCVVNAHLQAGGTRADVRDAQLKEVLEFLKR----- 140

                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767904159 237 slppLTISNHDVILWLGDLNYRIEELDVEKVKKLIEekdfqmlyaydqLKIQVAAKTVFEgftegELTFQPTykydtgsd 316
Cdd:cd08372  141 ----LRQPNSAPVVICGDFNVRPSEVDSENPSSMLR------------LFVALNLVDSFE-----TLPHAYT-------- 191

                        250       260       270       280       290
                 ....*....|....*....|....*....|....*....|....*....|.
gi 767904159 317 dWDTSEKcRAPAWCDRILW--------KGKNITQLSYQSHMalkTSDHKPV 359
Cdd:cd08372  192 -FDTYMH-NVKSRLDYIFVsksllpsvKSSKILSDAARARI---PSDHYPI 237
RhoGAP-p50rhoGAP cd04404
RhoGAP-p50rhoGAP: RhoGAP (GTPase-activator protein [GAP] for Rho-like small GTPases) domain of ...
 556-692 2.30e-10

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


Pssm-ID: 239869 [Multi-domain]  Cd Length: 195  Bit Score: 60.43  E-value: 2.30e-10
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767904159 556 IPKELWMMVDYLYRNAVQQEDLFQQPGLRSEFEHIRDCLDTGMIDNLSASNHSVAEALLL--FLESLPEPVICYSTY--- 630
Cdd:cd04404   23 IPPVVRETVEYLQAHALTTEGIFRRSANTQVVKEVQQKYNMGEPVDFDQYEDVHLPAVILktFLRELPEPLLTFDLYddi 102

                         90       100       110       120       130       140
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 767904159 631 ---HNCLECSgNYTASKQVISTLPIFHKNVFHYLMAFLRELLKNSAKNHLDENILASIFGSLLLR 692
Cdd:cd04404  103 vgfLNVDKEE-RVERVKQLLQTLPEENYQVLKYLIKFLVQVSAHSDQNKMTNSNLAVVFGPNLLW 166
RhoGAP_nadrin cd04386
RhoGAP_nadrin: RhoGAP (GTPase-activator protein [GAP] for Rho-like small GTPases) domain of ...
 564-691 6.67e-09

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: 56.31  E-value: 6.67e-09
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767904159 564 VDYLYRNAVQQEDLFQQPGLRSEFEHIRDCLDTGMIDNLSASN----HSVAEALLLFLESLPEPVICYSTYHNCLECSG- 638
Cdd:cd04386   28 VMCLLETGMNEEGLFRVGGGASKLKRLKAALDAGTFSLPLDEFysdpHAVASALKSYLRELPDPLLTYNLYEDWVQAANk 107

                         90       100       110       120       130
                 ....*....|....*....|....*....|....*....|....*....|....*...
gi 767904159 639 -----NYTASKQVISTLPIFHKNVFHYLMAFLRELLKNSAKNHLDENILASIFGSLLL 691
Cdd:cd04386  108 pdedeRLQAIWRILNKLPRENRDNLRYLIKFLSKLAQKSDENKMSPSNIAIVLAPNLL 165
RhoGAP_chimaerin cd04372
RhoGAP_chimaerin: RhoGAP (GTPase-activator protein [GAP] for Rho-like small GTPases) domain of ...
 553-706 9.23e-09

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: 55.99  E-value: 9.23e-09
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767904159 553 PMEIPKELWMMVDYLYRNAVQQEDLFQQPGLRSEFEHIRDCLDT-GMIDNLSASNHS----VAEALLLFLESLPEPVICY 627
Cdd:cd04372   13 NTQRPMVVDMCIREIEARGLQSEGLYRVSGFAEEIEDVKMAFDRdGEKADISATVYPdinvITGALKLYFRDLPIPVITY 92

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767904159 628 STYHNCLECS--GNY----TASKQVISTLPIFHKNVFHYLMAFLRELLKNSAKNHLDENILASIFGSLLLRNP---AGHQ 698
Cdd:cd04372   93 DTYPKFIDAAkiSNPderlEAVHEALMLLPPAHYETLRYLMEHLKRVTLHEKDNKMNAENLGIVFGPTLMRPPedsALTT 172


                 ....*...
gi 767904159 699 KLDMTEKK 706
Cdd:cd04372  173 LNDMRYQI 180
RhoGAP_ARHGAP20 cd04402
RhoGAP_ARHGAP20: RhoGAP (GTPase-activator protein [GAP] for Rho-like small GTPases) domain of ...
 557-716 4.09e-08

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: 53.84  E-value: 4.09e-08
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767904159 557 PKELWMMVDYLYRNAVQQEDLFQQPGLRSEFEHIRDCLDTGMIDNLSASN-HSVAEALLLFLESLPEPVICYSTYHNCLE 635
Cdd:cd04402   16 PKPILDMLSLLYQKGPSTEGIFRRSANAKACKELKEKLNSGVEVDLKAEPvLLLASVLKDFLRNIPGSLLSSDLYEEWMS 95

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767904159 636 C------SGNYTASKQVISTLPIFHKNVFHYLMAFLRELLKNSAKNHLDENILASIFGSLLLRNPAGhQKLDMTEKKKAQ 709
Cdd:cd04402   96 AldqeneEEKIAELQRLLDKLPRPNVLLLKHLICVLHNISQNSETNKMDAFNLAVCIAPSLLWPPAS-SELQNEDLKKVT 174


                 ....*..
gi 767904159 710 EFIhQFL 716
Cdd:cd04402  175 SLV-QFL 180
RhoGAP_GMIP_PARG1 cd04378
RhoGAP_GMIP_PARG1: RhoGAP (GTPase-activator protein [GAP] for Rho-like small GTPases) domain ...
 544-703 5.66e-08

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: 53.58  E-value: 5.66e-08
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767904159 544 GDDGSQL--DSPMEIPKELWMMVDYLYRNAVQQEDLFQQPGLRSEFEHIRDCLDTGM--IDNLSASNHSVAEALLLFLES 619
Cdd:cd04378    2 GVDFSQVprDFPDEVPFIIKKCTSEIENRALGVQGIYRVSGSKARVEKLCQAFENGKdlVELSELSPHDISSVLKLFLRQ 81

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767904159 620 LPEPVICYSTYHN--------------------CLECSGNYTASKQVISTLPIFHKNVFHYLMAFLRELLKNSAKNHLDE 679
Cdd:cd04378   82 LPEPLILFRLYNDfialakeiqrdteedkapntPIEVNRIIRKLKDLLRQLPASNYNTLQHLIAHLYRVAEQFEENKMSP 161

                        170       180
                 ....*....|....*....|....
gi 767904159 680 NILASIFGSLLLRNPAGHQKLDMT 703
Cdd:cd04378  162 NNLGIVFGPTLIRPRPGDADVSLS 185
RhoGAP-ARHGAP11A cd04394
RhoGAP-ARHGAP11A: RhoGAP (GTPase-activator protein [GAP] for Rho-like small GTPases) domain of ...
 572-711 9.38e-08

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: 52.86  E-value: 9.38e-08
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767904159 572 VQQEDLFQQPGLRSEFEHIRDCLDTGMIDNLSASNHSVAEALLLFLESLPEPVICYSTYHNCLECSGNYTASKQVIST-- 649
Cdd:cd04394   35 LSTEGLFRKSGSVVRQKELKAKLEGGEACLSSALPCDVAGLLKQFFRELPEPLLPYDLHEALLKAQELPTDEERKSATll 114

                         90       100       110       120       130       140
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 767904159 650 ----LPIFHKNVFHYLMAFLRELLKNSAKNHLDENILASIFGSLLLRNPAGHQKLDMTEKKKAQEF 711
Cdd:cd04394  115 ltclLPDEHVNTLRYFFSFLYDVAQRCSENKMDSSNLAVIFAPNLFQSEEGGEKMSSSTEKRLRLQ 180
RhoGAP_p85 cd04388
RhoGAP_p85: RhoGAP (GTPase-activator protein [GAP] for Rho-like small GTPases) domain present ...
 552-695 5.32e-07

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: 50.64  E-value: 5.32e-07
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767904159 552 SPMEI-PKELWMMVDYLYRNAVQQEDLF--QQPGLRSEFEHIRDClDTGMIDNLSASNHSVAEALLLFLESLPEPVICYS 628
Cdd:cd04388   10 SPPDVaPPLLIKLVEAIEKKGLESSTLYrtQSSSSLTELRQILDC-DAASVDLEQFDVAALADALKRYLLDLPNPVIPAP 88

                         90       100       110       120       130       140       150
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 767904159 629 TYHNCLECSGNYTASKQVI---------STLPIFHKNVFHYLMAFLRELLKNSAKNHLDENILASIFGSLLLRNPA 695
Cdd:cd04388   89 VYSEMISRAQEVQSSDEYAqllrklirsPNLPHQYWLTLQYLLKHFFRLCQSSSKNLLSARALAEIFSPLLFRFQP 164
RhoGAP_GMIP cd04408
RhoGAP_GMIP: RhoGAP (GTPase-activator protein [GAP] for Rho-like small GTPases) domain of GMIP ...
 544-696 5.43e-07

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: 50.59  E-value: 5.43e-07
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767904159 544 GDDGSQL--DSPMEIPKELWMMVDYLYRNAVQQEDLFQQPGLRSEFEHIRDCLDTG--MIDNLSASNHSVAEALLLFLES 619
Cdd:cd04408    2 GVDFSQLprDFPEEVPFVVVRCTAEIENRALGVQGIYRISGSKARVEKLCQAFENGrdLVDLSGHSPHDITSVLKHFLKE 81

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767904159 620 LPEPVICYSTYHNCLECSGNYTAS------------------KQVISTLPIFHKNVFHYLMAFLRELLKNSAKNHLDENI 681
Cdd:cd04408   82 LPEPVLPFQLYDDFIALAKELQRDsekaaespsiveniirslKELLGRLPVSNYNTLRHLMAHLYRVAERFEDNKMSPNN 161

                        170
                 ....*....|....*
gi 767904159 682 LASIFGSLLLRNPAG 696
Cdd:cd04408  162 LGIVFGPTLLRPLVG 176
RhoGAP_ARHGAP6 cd04376
RhoGAP_ARHGAP6: RhoGAP (GTPase-activator protein [GAP] for Rho-like small GTPases) domain of ...
 583-714 6.77e-07

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: 50.52  E-value: 6.77e-07
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767904159 583 LRSEFEHIrdcLDTGMIDNLSAsnHSVAEALLLFLESLPEPVIC---YSTYHNC--LECSGNYTASKQVISTLPIFHKNV 657
Cdd:cd04376   43 LREEFDRG---IDVVLDENHSV--HDVAALLKEFFRDMPDPLLPrelYTAFIGTalLEPDEQLEALQLLIYLLPPCNCDT 117

                         90       100       110       120       130       140
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 767904159 658 FHYLMAFLRELLKNSAKNH-----------LDENILASIFGSLLLRNPAGHQKLDMTEKKKAQEFIHQ 714
Cdd:cd04376  118 LHRLLKFLHTVAEHAADSIdedgqevsgnkMTSLNLATIFGPNLLHKQKSGEREFVQASLRIEESTAI 185
RhoGAP_p190 cd04373
RhoGAP_p190: RhoGAP (GTPase-activator protein [GAP] for Rho-like small GTPases) domain of ...
 552-692 1.04e-06

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


Pssm-ID: 239838  Cd Length: 185  Bit Score: 49.76  E-value: 1.04e-06
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767904159 552 SPMEIPKELWMMVDYLYRNAVQQEDLFQQPGLRSEFEHIRDCLDTGMIDNLSASN---HSVAEALLLFLESLPEPVICYS 628
Cdd:cd04373   11 SEKPIPIFLEKCVEFIEATGLETEGIYRVSGNKTHLDSLQKQFDQDHNLDLVSKDftvNAVAGALKSFFSELPDPLIPYS 90

                         90       100       110       120       130       140       150
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767904159 629 TYHNCLECSG------NYTASKQVISTLPIFHKNVFHYLMAFLRELLKNSAKNHLDENILASIFGSLLLR 692
Cdd:cd04373   91 MHLELVEAAKindreqRLHALKELLKKFPPENFDVFKYVITHLNKVSQNSKVNLMTSENLSICFWPTLMR 160
RhoGAP_fRGD1 cd04398
RhoGAP_fRGD1: RhoGAP (GTPase-activator protein [GAP] for Rho-like small GTPases) domain of ...
 583-712 1.15e-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: 49.71  E-value: 1.15e-06
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767904159 583 LRSEFEHIRDCLDTGMIDNLSASNHSVAEALLLFLESLPEPVICYSTYHNCLECsGNYT-------ASKQVISTLPIFHK 655
Cdd:cd04398   50 LKELFDKDPLNVLLISPEDYESDIHSVASLLKLFFRELPEPLLTKALSREFIEA-AKIEdesrrrdALHGLINDLPDANY 128

                         90       100       110       120       130
                 ....*....|....*....|....*....|....*....|....*....|....*..
gi 767904159 656 NVFHYLMAFLRELLKNSAKNHLDENILASIFGSLLLrNPAGHQKLDMTEKKKAQEFI 712
Cdd:cd04398  129 ATLRALMFHLARIKEHESVNRMSVNNLAIIWGPTLM-NAAPDNAADMSFQSRVIETL 184
RhoGAP_ARHGAP21 cd04395
RhoGAP_ARHGAP21: RhoGAP (GTPase-activator protein [GAP] for Rho-like small GTPases) domain of ...
 607-694 1.98e-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: 48.94  E-value: 1.98e-06
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767904159 607 HSVAEALLLFLESLPEPVICYSTYHNCLECSGNYTAS------KQVISTLPIFHKNVFHYLMAFLRELLKNSAKNHLDEN 680
Cdd:cd04395   74 NVVSSLLKSFFRKLPEPLFTNELYPDFIEANRIEDPVerlkelRRLIHSLPDHHYETLKHLIRHLKTVADNSEVNKMEPR 153

                         90
                 ....*....|....
gi 767904159 681 ILASIFGSLLLRNP 694
Cdd:cd04395  154 NLAIVFGPTLVRTS 167
RhoGAP_DLC1 cd04375
RhoGAP_DLC1: RhoGAP (GTPase-activator protein [GAP] for Rho-like small GTPases) domain of ...
 556-710 1.00e-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: 47.41  E-value: 1.00e-05
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767904159 556 IPKELWMMVDYLYRNAVQQEDLFQQPGLRSEFEHIRDCL----DTGMIDNLSAsnHSVAEALLLFLESLPEPVICY---S 628
Cdd:cd04375   20 LPRSIQQAMRWLRNNALDQVGLFRKSGVKSRIQKLRSMIesstDNVNYDGQQA--YDVADMLKQYFRDLPEPLLTNklsE 97

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767904159 629 TYHNCLECSGNY---TASKQVISTLPIFHKNVFHYLMAFLRELLKNSAKNHLDENILA-----SIFGSLLLR----NPAG 696
Cdd:cd04375   98 TFIAIFQYVPKEqrlEAVQCAILLLPDENREVLQTLLYFLSDVAANSQENQMTATNLAvclapSLFHLNTSRrensSPAR 177

                        170       180
                 ....*....|....*....|....
gi 767904159 697 HQKL----------DMTEKKKAQE 710
Cdd:cd04375  178 RMQRkkslgkpdqkELSENKAAHQ 201
RhoGAP_myosin_IX cd04377
RhoGAP_myosin_IX: RhoGAP (GTPase-activator protein [GAP] for Rho-like small GTPases) domain ...
 556-694 1.31e-05

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: 46.28  E-value: 1.31e-05
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767904159 556 IPKELWMMVDYLYRNAVQQEDLFQQPGLRSEFEHIRDCLDTGMiDNLSASN---HSVAEALLLFLESLPEPVICYSTYHN 632
Cdd:cd04377   15 VPLVLEKLLEHIEMHGLYTEGIYRKSGSANKIKELRQGLDTDP-DSVNLEDypiHVITSVLKQWLRELPEPLMTFELYEN 93

                         90       100       110       120       130       140
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 767904159 633 CLECSGNYTASKQ------VISTLPIFHKNVFHYLMAFLRELLKNSAKNHLDENILASIFGSLLLRNP 694
Cdd:cd04377   94 FLRAMELEEKQERvralysVLEQLPRANLNTLERLIFHLVRVALQEEVNRMSANALAIVFAPCILRCP 161
RhoGAP_ARHGAP19 cd04392
RhoGAP_ARHGAP19: RhoGAP (GTPase-activator protein [GAP] for Rho-like small GTPases) domain of ...
 559-691 2.08e-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: 46.30  E-value: 2.08e-05
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767904159 559 ELWMMVDYLYRNaVQQEDLFQQPGLRSEFEHIRDCLDTGMIDNLSA---SNHSVAEALLLFLESLPEPVICYSTYHNCLE 635
Cdd:cd04392   12 QIYQLIEYLEKN-LRVEGLFRKPGNSARQQELRDLLNSGTDLDLESggfHAHDCATVLKGFLGELPEPLLTHAHYPAHLQ 90

                         90       100       110       120       130       140       150
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 767904159 636 CS--------GNYTASKQ----------VISTLPIFHKNVFHYLMAFLRELLKNSAKNHLDENILASIFGSLLL 691
Cdd:cd04392   91 IAdlcqfdekGNKTSAPDkerllealqlLLLLLPEENRNLLKLILDLLYQTAKHEDKNKMSADNLALLFTPHLI 164
RhoGAP_CdGAP cd04384
RhoGAP_CdGAP: RhoGAP (GTPase-activator protein [GAP] for Rho-like small GTPases) domain of ...
 577-695 2.31e-05

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: 45.96  E-value: 2.31e-05
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767904159 577 LFQQPGLRSEFEHIRDCLDTGMIDNLSASN-----HSVAEALLLFLESLPEPVICYSTYHNCLECSGNYTASKQ------ 645
Cdd:cd04384   38 IYRLSGIASNIQRLRHEFDSEQIPDLTKDVyiqdiHSVSSLCKLYFRELPNPLLTYQLYEKFSEAVSAASDEERlekihd 117

                         90       100       110       120       130
                 ....*....|....*....|....*....|....*....|....*....|
gi 767904159 646 VISTLPIFHKNVFHYLMAFLRELLKNSAKNHLDENILASIFGSLLLRNPA 695
Cdd:cd04384  118 VIQQLPPPHYRTLEFLMRHLSRLAKYCSITNMHAKNLAIVWAPNLLRSKQ 167
RhoGAP_myosin_IXB cd04407
RhoGAP_myosin_IXB: RhoGAP (GTPase-activator protein [GAP] for Rho-like small GTPases) domain ...
 547-694 2.75e-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: 45.37  E-value: 2.75e-05
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767904159 547 GSQLDSPMEIPKELWMMVDYLYRNAVQQEDLFQQPGLRSEFEHIRDCLDTGMiDNLSASN---HSVAEALLLFLESLPEP 623
Cdd:cd04407    6 GSLTSNKTSVPIVLEKLLEHVEMHGLYTEGIYRKSGSANRMKELHQLLQADP-ENVKLENypiHAITGLLKQWLRELPEP 84

                         90       100       110       120       130       140       150
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 767904159 624 VICYSTYHNCL------ECSGNYTASKQVISTLPIFHKNVFHYLMAFLRELLKNSAKNHLDENILASIFGSLLLRNP 694
Cdd:cd04407   85 LMTFAQYNDFLravelpEKQEQLQAIYRVLEQLPTANHNTLERLIFHLVKVALEEDVNRMSPNALAIVFAPCLLRCP 161
RhoGAP_fBEM3 cd04400
RhoGAP_fBEM3: RhoGAP (GTPase-activator [GAP] protein for Rho-like small GTPases) domain of ...
 556-691 5.51e-05

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: 44.66  E-value: 5.51e-05
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767904159 556 IPKELWMMVDYLY-RNAVQQEDLFQQPGLRSEFEHIRDCLDTGMIDNLSASN-----HSVAEALLLFLESLPEPVICYST 629
Cdd:cd04400   22 LPSVVYRCIEYLDkNRAIYEEGIFRLSGSASVIKQLKERFNTEYDVDLFSSSlypdvHTVAGLLKLYLRELPTLILGGEL 101

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767904159 630 yHNCLECSGNYTAS--------KQVISTLPIFHKNVFHYLMAFLRELLKNSAKNHLDE-----------NILASIFGSLL 690
Cdd:cd04400  102 -HNDFKRLVEENHDrsqralelKDLVSQLPQANYDLLYVLFSFLRKIIEHSDVNKMNLrnvcivfsptlNIPAGIFVLFL 180


                 .
gi 767904159 691 L 691
Cdd:cd04400  181 T 181
RhoGAP_Bcr cd04387
RhoGAP_Bcr: RhoGAP (GTPase-activator protein [GAP] for Rho-like small GTPases) domain of Bcr ...
 564-710 1.72e-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: 43.38  E-value: 1.72e-04
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767904159 564 VDYLYRNAVQQEDLFQQPGLRSEFEHIRDCLDTGMIDNLSASN----HSVAEALLLFLESLPEPVIC---YSTYHNCLEC 636
Cdd:cd04387   24 VEEVERRGMEEVGIYRISGVATDIQALKAAFDTNNKDVSVMLSemdvNAIAGTLKLYFRELPEPLFTdelYPNFAEGIAL 103

                         90       100       110       120       130       140       150
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 767904159 637 SGNYTASKQVIS---TLPIFHKNVFHYLMAFLRELLKNSAKNHLDENILASIFGSLLLRNPAGHQKLDMTEKKKAQE 710
Cdd:cd04387  104 SDPVAKESCMLNlllSLPDPNLVTFLFLLHHLKRVAEREEVNKMSLHNLATVFGPTLLRPSEKESKIPTNTMTDSWS 180
RhoGAP_ARHGAP27_15_12_9 cd04403
RhoGAP_ARHGAP27_15_12_9: GTPase-activator protein (GAP) domain for Rho-like GTPases found in ...
 607-712 2.38e-04

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: 42.76  E-value: 2.38e-04
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767904159 607 HSVAEALLLFLESLPEPVICYS---TYHNCLECSGNYTASKQV---ISTLPIFHKNVFHYLMAFLRELLKNSAKNHLDEN 680
Cdd:cd04403   71 HVITGALKLFFRELPEPLFPYSlfnDFVAAIKLSDYEQRVSAVkdlIKSLPKPNHDTLKMLFRHLCRVIEHGEKNRMTTQ 150

                         90       100       110
                 ....*....|....*....|....*....|....
gi 767904159 681 ILASIFGSLLLRNP--AGHQKLDMTEKKKAQEFI 712
Cdd:cd04403  151 NLAIVFGPTLLRPEqeTGNIAVHMVYQNQIVELI 184
INPP5A cd09092
Type I inositol polyphosphate 5-phosphatase I; Type I inositol polyphosphate 5-phosphatase I ...
 185-365 8.59e-04

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: 42.46  E-value: 8.59e-04
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767904159 185 GNKGGVAIRFQFHNTSICVVNSHL---AAHIEEYERRNQDYKDICSRMQfcqpDPSLPPLTISNHDVILWL--GDLNYRI 259
Cdd:cd09092  153 SRKGFMRTRWKINNCVFDLVNIHLfhdASNLAACESSPSVYSQNRHRAL----GYVLERLTDERFEKVPFFvfGDFNFRL 228

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767904159 260 EELDV-------------------EKVKKLIEEKDFQ---------MLYAY-DQ-----------LKIQVAAKTVFEGFT 299
Cdd:cd09092  229 DTKSVvetlcakatmqtvrkadsnIVVKLEFREKDNDnkvvlqiekKKFDYfNQdvfrdnngkalLKFDKELEVFKDVLY 308

                        170       180       190       200       210       220       230
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 767904159 300 EGELTFQPTYKYdtgSDDWDTSE---KCRAPAWCDRILWKgKNITQLSYQSH----------MALKTSDHKPVSSVFDI 365
Cdd:cd09092  309 ELDISFPPSYPY---SEDPEQGTqymNTRCPAWCDRILMS-HSARELKSENEeksvtydmigPNVCMGDHKPVFLTFRI 383
RhoGAP_ARHGAP18 cd04391
RhoGAP_ARHGAP18: RhoGAP (GTPase-activator protein [GAP] for Rho-like small GTPases) domain of ...
 548-675 3.28e-03

RhoGAP_ARHGAP18: RhoGAP (GTPase-activator protein [GAP] for Rho-like small GTPases) domain of ArhGAP18-like proteins. The function of ArhGAP18 is unknown. Small GTPases cluster into distinct families, and all act as molecular switches, active in their GTP-bound form but inactive when GDP-bound. The Rho family of GTPases activates effectors involved in a wide variety of developmental processes, including regulation of cytoskeleton formation, cell proliferation and the JNK signaling pathway. GTPases generally have a low intrinsic GTPase hydrolytic activity but there are family-specific groups of GAPs that enhance the rate of GTP hydrolysis by several orders of magnitude.


Pssm-ID: 239856  Cd Length: 216  Bit Score: 39.64  E-value: 3.28e-03
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767904159 548 SQLDSPMEIPKELWMMVDYLYRNAVQQEDLFQQPGLRSEFEHIRDCLDT----GMIDNLSASNHSVAEALLLFLESLPEP 623
Cdd:cd04391   14 QKKVPGSKVPLIFQKLINKLEERGLETEGILRIPGSAQRVKFLCQELEAkfyeGTFLWDQVKQHDAASLLKLFIRELPQP 93

                         90       100       110       120       130
                 ....*....|....*....|....*....|....*....|....*....|....*...
gi 767904159 624 VICYSTYHNCLECSGNYTASKQV------ISTLPIFHKNVFHYLMAFLRELLKNSAKN 675
Cdd:cd04391   94 LLTVEYLPAFYSVQGLPSKKDQLqalnllVLLLPEANRDTLKALLEFLQKVVDHEEKN 151
RhoGAP_MgcRacGAP cd04382
RhoGAP_MgcRacGAP: RhoGAP (GTPase-activator protein [GAP] for Rho-like small GTPases) domain ...
 552-687 7.54e-03

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


Pssm-ID: 239847  Cd Length: 193  Bit Score: 38.43  E-value: 7.54e-03
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767904159 552 SPMeIPKELWMMVDYLYRNAVQQEDLFQQPGLRSEFEHIRDCLDTG-MIDNLSASN-HSVAEALLLFLESLPEPVICYST 629
Cdd:cd04382   14 SPM-IPALIVHCVNEIEARGLTEEGLYRVSGSEREVKALKEKFLRGkTVPNLSKVDiHVICGCLKDFLRSLKEPLITFAL 92

                         90       100       110       120       130       140
                 ....*....|....*....|....*....|....*....|....*....|....*....|....
gi 767904159 630 YHNCLECSGNY------TASKQVISTLPIFHKNVFHYLMAFLRELLKNSAkNHLDENILASIFG 687
Cdd:cd04382   93 WKEFMEAAEILdednsrAALYQAISELPQPNRDTLAFLILHLQRVAQSPE-CKMDINNLARVFG 155
RhoGAP_ARAP cd04385
RhoGAP_ARAP: RhoGAP (GTPase-activator protein [GAP] for Rho-like small GTPases) domain present ...
 564-712 8.47e-03

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


Pssm-ID: 239850  Cd Length: 184  Bit Score: 38.06  E-value: 8.47e-03
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767904159 564 VDYLYRNAVQQEDLFQQPGLRS-------EFEhiRDCLDTGMIDNlSASNHSVAEALLLFLESLPEPVICYSTYHNCLEC 636
Cdd:cd04385   23 IDFITQHGLMSEGIYRKNGKNSsvkklleAFR--KDARSVQLREG-EYTVHDVADVLKRFLRDLPDPLLTSELHAEWIEA 99

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767904159 637 SGNYTAS------KQVISTLPIFHKNVFHYLMAFLRELLKNSAKNHLDENILASIFGSLLLRNPAGHQKLDMTEKKKAQE 710
Cdd:cd04385  100 AELENKDeriaryKELIRRLPPINRATLKVLIGHLYRVQKHSDENQMSVHNLALVFGPTLFQTDEHSVGQTSHEVKVIED 179


                 ..
gi 767904159 711 FI 712
Cdd:cd04385  180 LI 181
 
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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