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Conserved domains on  [gi|741922299|ref|XP_010802104|]
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type II inositol 1,4,5-trisphosphate 5-phosphatase isoform X3 [Bos taurus]

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 ...
105-398 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: 576.19  E-value: 0e+00
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 741922299 105 FRFFVGTYNVNGQSPKECLRPWLSHDTQAPDVYCVGFQELDLSKEAFFFHDTPKEEEWFKAVSEALHPDAKYAKVKLIRL 184
Cdd:cd09093    1 FRIFVGTWNVNGQSPDESLRPWLSCDEEPPDIYAIGFQELDLSAEAFLFNDSSREQEWVKAVERGLHPDAKYKKVKLIRL 80
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 741922299 185 VGIMLLLYVKQEHAAYISEVEAETVGTGIMGRMGNKGGVAIRFQFHNTSICVVNSHLAAHTEEYERRNQDYKDICSRMQF 264
Cdd:cd09093   81 VGMMLLVFVKKEHRQHIKEVAAETVGTGIMGKMGNKGGVAVRFQFHNTTFCFVNSHLAAHMEEVERRNQDYKDICARMKF 160
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 741922299 265 CqvDPSLPPLTISKHDVILWLGDLNYRIEDPDVEKVKKLIEEKAFQTLYAYDQLRAQVAAKAVFEGFSEGELTFQPTYKY 344
Cdd:cd09093  161 E--DPDGPPLSISDHDVVFWLGDLNYRIQELPTEEVKELIEKNDLEELLKYDQLNIQRRAGKVFEGFTEGEINFIPTYKY 238
                        250       260       270       280       290
                 ....*....|....*....|....*....|....*....|....*....|....
gi 741922299 345 DTGSDDWDTSEKCRAPAWCDRVLWKGKNITQLSYQSHMALKTSDHKPVSSVFDI 398
Cdd:cd09093  239 DPGTDNWDSSEKCRAPAWCDRILWRGTNIVQLSYRSHMELKTSDHKPVSALFDI 292
RhoGAP_OCRL1 cd04380
RhoGAP_OCRL1: RhoGAP (GTPase-activator protein [GAP] for Rho-like small GTPases) domain ...
532-749 1.33e-82

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: 262.28  E-value: 1.33e-82
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 741922299 532 FLSVSGNYIPSCFGSPIHTLCYMKEPILDLPLEtireltlmQLQTEDNGSQLEKPMDIPKELWILVDYLYRNAIQQEDLF 611
Cdd:cd04380    1 FITVTGVYLPSCFGSSLETLIRLPDPGIRNLID--------QLELGDNPDYSEVPLSIPKEIWRLVDYLYTRGLAQEGLF 72
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 741922299 612 QQPGLRSEFDH----IRDCLDTGMIDNLSASNHSVAEALLLFLESLPEPVICYSAYRNCLECSGNLA-ASKQVI-TALPA 685
Cdd:cd04380   73 EEPGLPSEPGEllaeIRDALDTGSPFNSPGSAESVAEALLLFLESLPDPIIPYSLYERLLEAVANNEeDKRQVIrISLPP 152
                        170       180       190       200       210       220
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 741922299 686 CHRNVFTYLMAFLQELLKNSAKNHLDDNILASIFGSLLLRNPAGHQ-KLEMAEKKKAQEFVHQFL 749
Cdd:cd04380  153 VHRNVFVYLCSFLRELLSESADRGLDENTLATIFGRVLLRDPPRAGgKERRAERDRKRAFIEQFL 217
 
Name Accession Description Interval E-value
INPP5c_INPP5B cd09093
Catalytic inositol polyphosphate 5-phosphatase (INPP5c) domain of Type II inositol ...
105-398 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: 576.19  E-value: 0e+00
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 741922299 105 FRFFVGTYNVNGQSPKECLRPWLSHDTQAPDVYCVGFQELDLSKEAFFFHDTPKEEEWFKAVSEALHPDAKYAKVKLIRL 184
Cdd:cd09093    1 FRIFVGTWNVNGQSPDESLRPWLSCDEEPPDIYAIGFQELDLSAEAFLFNDSSREQEWVKAVERGLHPDAKYKKVKLIRL 80
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 741922299 185 VGIMLLLYVKQEHAAYISEVEAETVGTGIMGRMGNKGGVAIRFQFHNTSICVVNSHLAAHTEEYERRNQDYKDICSRMQF 264
Cdd:cd09093   81 VGMMLLVFVKKEHRQHIKEVAAETVGTGIMGKMGNKGGVAVRFQFHNTTFCFVNSHLAAHMEEVERRNQDYKDICARMKF 160
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 741922299 265 CqvDPSLPPLTISKHDVILWLGDLNYRIEDPDVEKVKKLIEEKAFQTLYAYDQLRAQVAAKAVFEGFSEGELTFQPTYKY 344
Cdd:cd09093  161 E--DPDGPPLSISDHDVVFWLGDLNYRIQELPTEEVKELIEKNDLEELLKYDQLNIQRRAGKVFEGFTEGEINFIPTYKY 238
                        250       260       270       280       290
                 ....*....|....*....|....*....|....*....|....*....|....
gi 741922299 345 DTGSDDWDTSEKCRAPAWCDRVLWKGKNITQLSYQSHMALKTSDHKPVSSVFDI 398
Cdd:cd09093  239 DPGTDNWDSSEKCRAPAWCDRILWRGTNIVQLSYRSHMELKTSDHKPVSALFDI 292
IPPc smart00128
Inositol polyphosphate phosphatase, catalytic domain homologues; Mg(2+)-dependent/Li(+) ...
103-400 4.84e-113

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


Pssm-ID: 214525 [Multi-domain]  Cd Length: 306  Bit Score: 344.72  E-value: 4.84e-113
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 741922299   103 QNFRFFVGTYNVNGQS-PKECLRPWL-----SHDTQAPDVYCVGFQELDLSKE-AFFFHDTPKEEEWFKAVSEALHPDAK 175
Cdd:smart00128   1 RDIKVLIGTWNVGGLEsPKVDVTSWLfqkieVKQSEKPDIYVIGLQEVVGLAPgVILETIAGKERLWSDLLESSLNGDGQ 80
                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 741922299   176 YAKVKLIRLVGIMLLLYVKQEHAAYISEVEAETVGTGIMGRMGNKGGVAIRFQFHNTSICVVNSHLAAHTEEYERRNQDY 255
Cdd:smart00128  81 YNVLAKVYLVGILVLVFVKANHLVYIKDVETFTVKTGMGGLWGNKGAVAVRFKLSDTSFCFVNSHLAAGASNVEQRNQDY 160
                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 741922299   256 KDICSRMQFcqvdPSLPPLTISKHDVILWLGDLNYRIEDPDVEKVKKLIEEKAFQTLYAYDQLRAQVAAKAVFEGFSEGE 335
Cdd:smart00128 161 KTILRALSF----PERALLSQFDHDVVFWFGDLNFRLDSPSYEEVRRKISKKEFDDLLEKDQLNRQREAGKVFKGFQEGP 236
                          250       260       270       280       290       300
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 741922299   336 LTFQPTYKYDT-GSDDWDTSEKCRAPAWCDRVLWK--GKNITQLS-YQSHMALKTSDHKPVSSVFDIGV 400
Cdd:smart00128 237 ITFPPTYKYDSvGTETYDTSEKKRVPAWCDRILYRsnGPELIQLSeYHSGMEITTSDHKPVFATFRLKV 305
RhoGAP_OCRL1 cd04380
RhoGAP_OCRL1: RhoGAP (GTPase-activator protein [GAP] for Rho-like small GTPases) domain ...
532-749 1.33e-82

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: 262.28  E-value: 1.33e-82
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 741922299 532 FLSVSGNYIPSCFGSPIHTLCYMKEPILDLPLEtireltlmQLQTEDNGSQLEKPMDIPKELWILVDYLYRNAIQQEDLF 611
Cdd:cd04380    1 FITVTGVYLPSCFGSSLETLIRLPDPGIRNLID--------QLELGDNPDYSEVPLSIPKEIWRLVDYLYTRGLAQEGLF 72
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 741922299 612 QQPGLRSEFDH----IRDCLDTGMIDNLSASNHSVAEALLLFLESLPEPVICYSAYRNCLECSGNLA-ASKQVI-TALPA 685
Cdd:cd04380   73 EEPGLPSEPGEllaeIRDALDTGSPFNSPGSAESVAEALLLFLESLPDPIIPYSLYERLLEAVANNEeDKRQVIrISLPP 152
                        170       180       190       200       210       220
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 741922299 686 CHRNVFTYLMAFLQELLKNSAKNHLDDNILASIFGSLLLRNPAGHQ-KLEMAEKKKAQEFVHQFL 749
Cdd:cd04380  153 VHRNVFVYLCSFLRELLSESADRGLDENTLATIFGRVLLRDPPRAGgKERRAERDRKRAFIEQFL 217
COG5411 COG5411
Phosphatidylinositol 5-phosphate phosphatase [Signal transduction mechanisms];
92-406 3.07e-72

Phosphatidylinositol 5-phosphate phosphatase [Signal transduction mechanisms];


Pssm-ID: 227698 [Multi-domain]  Cd Length: 460  Bit Score: 243.15  E-value: 3.07e-72
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 741922299  92 LIQKEEDYTYIQNFRFFVGTYNVNGQSPKECLRPWLSHD---TQAPDVYCVGFQE-LDLSKEAFFFHDT-----PKEEEW 162
Cdd:COG5411   17 LRQRRSKYVIEKDVSIFVSTFNPPGKPPKASTKRWLFPEieaTELADLYVVGLQEvVELTPGSILSADPydrlrIWESKV 96
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 741922299 163 FKAVSEALHpDAKYAKVKLIRLVGIMLLLYVKQEHAAYISEVEAETVGTGIMGRMGNKGGVAIRFQFHNTSICVVNSHLA 242
Cdd:COG5411   97 LDCLNGAQS-DEKYSLLRSPQLGGILLRVFSLATNLPVVKPVSGTVKKTGFGGSSSNKGAVAIRFNYERTSFCFVNSHLA 175
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 741922299 243 AHTEEYERRNQDYKDICSrmqfCQVDPSlpPLTISKHDVILWLGDLNYRIeDPDVEKVKKLIE--EKAFQTLYAYDQLRA 320
Cdd:COG5411  176 AGVNNIEERIFDYRSIAS----NICFSR--GLRIYDHDTIFWLGDLNYRV-TSTNEEVRPEIAsdDGRLDKLFEYDQLLW 248
                        250       260       270       280       290       300       310       320
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 741922299 321 QVAAKAVFEGFSEGELTFQPTYKYDTGSDDWDTSEKCRAPAWCDRVLWKGKNITQLSYQSHMALKTSDHKPVSSVFDIGV 400
Cdd:COG5411  249 EMEVGNVFPGFKEPVITFPPTYKFDYGTDEYDTSDKGRIPSWTDRILYKSEQLTPHSYSSIPHLMISDHRPVYATFRAKI 328

                 ....*.
gi 741922299 401 RVINEE 406
Cdd:COG5411  329 KVVDPS 334
PLN03191 PLN03191
Type I inositol-1,4,5-trisphosphate 5-phosphatase 2; Provisional
153-412 3.29e-57

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


Pssm-ID: 215624 [Multi-domain]  Cd Length: 621  Bit Score: 206.30  E-value: 3.29e-57
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 741922299 153 FHDTPKEEEWFKAVSEALHPDAKYAKVKLIRLVGIMLLLYVKQEHAAYISEVEAETVGTGIMGRMGNKGGVAIRFQFHNT 232
Cdd:PLN03191 341 FKEVPSYQLPEDLIKDCRKVKQKYVRIVSKQMVGIYVSVWVRKRLRRHINNLKVSPVGVGLMGYMGNKGSVSISMSLFQS 420
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 741922299 233 SICVVNSHLAA-HTEEYE-RRNQDYKDICSRMQFCQVDPSLPPLTISKHDVILWLGDLNYRIEDPDVEkVKKLIEEKAFQ 310
Cdd:PLN03191 421 RLCFVCSHLTSgHKDGAEqRRNADVYEIIRRTRFSSVLDTDQPQTIPSHDQIFWFGDLNYRLNMLDTE-VRKLVAQKRWD 499
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 741922299 311 TLYAYDQLRAQVAAKAVFEGFSEGELTFQPTYKYDTGSDDW-----DTSEKCRAPAWCDRVLWKGKNITQLSYQsHMALK 385
Cdd:PLN03191 500 ELINSDQLIKELRSGHVFDGWKEGPIKFPPTYKYEINSDRYvgenpKEGEKKRSPAWCDRILWLGKGIKQLCYK-RSEIR 578
                        250       260
                 ....*....|....*....|....*..
gi 741922299 386 TSDHKPVSSVFDIGVRVINEELYRKTL 412
Cdd:PLN03191 579 LSDHRPVSSMFLVEVEVFDHRKLQRAL 605
RhoGAP smart00324
GTPase-activator protein for Rho-like GTPases; GTPase activator proteins towards Rho/Rac ...
588-752 1.01e-39

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


Pssm-ID: 214618  Cd Length: 174  Bit Score: 144.33  E-value: 1.01e-39
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 741922299   588 DIPKELWILVDYLYRNAIQQEDLFQQPGLRSEFDHIRDCLDTGMIDNL---SASNHSVAEALLLFLESLPEPVICYSAYR 664
Cdd:smart00324   2 PIPIIVEKCIEYLEKRGLDTEGIYRVSGSKSRVKELRDAFDSGPDPDLdlsEYDVHDVAGLLKLFLRELPEPLITYELYE 81
                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 741922299   665 NCLECSGN------LAASKQVITALPACHRNVFTYLMAFLQELLKNSAKNHLDDNILASIFGSLLLRNPAGHQKLEMaEK 738
Cdd:smart00324  82 EFIEAAKLedeterLRALRELLSLLPPANRATLRYLLAHLNRVAEHSEENKMTARNLAIVFGPTLLRPPDGEVASLK-DI 160
                          170
                   ....*....|....
gi 741922299   739 KKAQEFVHQFLTHP 752
Cdd:smart00324 161 RHQNTVIEFLIENA 174
RhoGAP pfam00620
RhoGAP domain; GTPase activator proteins towards Rho/Rac/Cdc42-like small GTPases.
590-728 9.21e-36

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


Pssm-ID: 459875  Cd Length: 148  Bit Score: 132.28  E-value: 9.21e-36
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 741922299  590 PKELWILVDYLYRNAIQQEDLFQQPGLRSEFDHIRDCLDTG---MIDNLSASNHSVAEALLLFLESLPEPVICYSAYRNC 666
Cdd:pfam00620   1 PLIVRKCVEYLEKRGLDTEGIFRVSGSASRIKELREAFDRGpdvDLDLEEEDVHVVASLLKLFLRELPEPLLTFELYEEF 80
                          90       100       110       120       130       140
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 741922299  667 LEC------SGNLAASKQVITALPACHRNVFTYLMAFLQELLKNSAKNHLDDNILASIFGSLLLRNPA 728
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 ...
105-398 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: 576.19  E-value: 0e+00
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 741922299 105 FRFFVGTYNVNGQSPKECLRPWLSHDTQAPDVYCVGFQELDLSKEAFFFHDTPKEEEWFKAVSEALHPDAKYAKVKLIRL 184
Cdd:cd09093    1 FRIFVGTWNVNGQSPDESLRPWLSCDEEPPDIYAIGFQELDLSAEAFLFNDSSREQEWVKAVERGLHPDAKYKKVKLIRL 80
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 741922299 185 VGIMLLLYVKQEHAAYISEVEAETVGTGIMGRMGNKGGVAIRFQFHNTSICVVNSHLAAHTEEYERRNQDYKDICSRMQF 264
Cdd:cd09093   81 VGMMLLVFVKKEHRQHIKEVAAETVGTGIMGKMGNKGGVAVRFQFHNTTFCFVNSHLAAHMEEVERRNQDYKDICARMKF 160
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 741922299 265 CqvDPSLPPLTISKHDVILWLGDLNYRIEDPDVEKVKKLIEEKAFQTLYAYDQLRAQVAAKAVFEGFSEGELTFQPTYKY 344
Cdd:cd09093  161 E--DPDGPPLSISDHDVVFWLGDLNYRIQELPTEEVKELIEKNDLEELLKYDQLNIQRRAGKVFEGFTEGEINFIPTYKY 238
                        250       260       270       280       290
                 ....*....|....*....|....*....|....*....|....*....|....
gi 741922299 345 DTGSDDWDTSEKCRAPAWCDRVLWKGKNITQLSYQSHMALKTSDHKPVSSVFDI 398
Cdd:cd09093  239 DPGTDNWDSSEKCRAPAWCDRILWRGTNIVQLSYRSHMELKTSDHKPVSALFDI 292
INPP5c cd09074
Catalytic domain of inositol polyphosphate 5-phosphatases; Inositol polyphosphate ...
105-398 5.68e-140

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: 414.04  E-value: 5.68e-140
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 741922299 105 FRFFVGTYNVNGQ-SPKECLRPWLS-HDTQAPDVYCVGFQELDLSKEAFF-FHDTPKEEEWFKAVSEALHPDAKYAKVKL 181
Cdd:cd09074    1 VKIFVVTWNVGGGiSPPENLENWLSpKGTEAPDIYAVGVQEVDMSVQGFVgNDDSAKAREWVDNIQEALNEKENYVLLGS 80
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 741922299 182 IRLVGIMLLLYVKQEHAAYIS--EVEAETVGTGIMGRMGNKGGVAIRFQFHNTSICVVNSHLAAHTEEYERRNQDYKDIC 259
Cdd:cd09074   81 AQLVGIFLFVFVKKEHLPQIKdlEVEGVTVGTGGGGKLGNKGGVAIRFQINDTSFCFVNSHLAAGQEEVERRNQDYRDIL 160
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 741922299 260 SRMQFCQvdPSLPPLTISKHDVILWLGDLNYRIEDPDVEkVKKLIEEKAFQTLYAYDQLRAQVAAKAVFEGFSEGELTFQ 339
Cdd:cd09074  161 SKLKFYR--GDPAIDSIFDHDVVFWFGDLNYRIDSTDDE-VRKLISQGDLDDLLEKDQLKKQKEKGKVFDGFQELPITFP 237
                        250       260       270       280       290       300
                 ....*....|....*....|....*....|....*....|....*....|....*....|..
gi 741922299 340 PTYKYDTGSDDWDTSEKCRAPAWCDRVLWK---GKNITQLSYQSHMALKTSDHKPVSSVFDI 398
Cdd:cd09074  238 PTYKFDPGTDEYDTSDKKRIPAWCDRILYKskaGSEIQPLSYTSVPLYKTSDHKPVRATFRV 299
IPPc smart00128
Inositol polyphosphate phosphatase, catalytic domain homologues; Mg(2+)-dependent/Li(+) ...
103-400 4.84e-113

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


Pssm-ID: 214525 [Multi-domain]  Cd Length: 306  Bit Score: 344.72  E-value: 4.84e-113
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 741922299   103 QNFRFFVGTYNVNGQS-PKECLRPWL-----SHDTQAPDVYCVGFQELDLSKE-AFFFHDTPKEEEWFKAVSEALHPDAK 175
Cdd:smart00128   1 RDIKVLIGTWNVGGLEsPKVDVTSWLfqkieVKQSEKPDIYVIGLQEVVGLAPgVILETIAGKERLWSDLLESSLNGDGQ 80
                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 741922299   176 YAKVKLIRLVGIMLLLYVKQEHAAYISEVEAETVGTGIMGRMGNKGGVAIRFQFHNTSICVVNSHLAAHTEEYERRNQDY 255
Cdd:smart00128  81 YNVLAKVYLVGILVLVFVKANHLVYIKDVETFTVKTGMGGLWGNKGAVAVRFKLSDTSFCFVNSHLAAGASNVEQRNQDY 160
                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 741922299   256 KDICSRMQFcqvdPSLPPLTISKHDVILWLGDLNYRIEDPDVEKVKKLIEEKAFQTLYAYDQLRAQVAAKAVFEGFSEGE 335
Cdd:smart00128 161 KTILRALSF----PERALLSQFDHDVVFWFGDLNFRLDSPSYEEVRRKISKKEFDDLLEKDQLNRQREAGKVFKGFQEGP 236
                          250       260       270       280       290       300
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 741922299   336 LTFQPTYKYDT-GSDDWDTSEKCRAPAWCDRVLWK--GKNITQLS-YQSHMALKTSDHKPVSSVFDIGV 400
Cdd:smart00128 237 ITFPPTYKYDSvGTETYDTSEKKRVPAWCDRILYRsnGPELIQLSeYHSGMEITTSDHKPVFATFRLKV 305
INPP5c_ScInp51p-like cd09090
Catalytic inositol polyphosphate 5-phosphatase (INPP5c) domain of Saccharomyces cerevisiae ...
106-396 2.00e-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: 306.19  E-value: 2.00e-98
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 741922299 106 RFFVGTYNVNGQSPKECLRPWL--SHDTQAPDVYCVGFQEL-DLSKEAFFFHDTPKEEEWFKAVSEAL--HPDAKYAKVK 180
Cdd:cd09090    2 NIFVGTFNVNGKSYKDDLSSWLfpEENDELPDIVVIGLQEVvELTAGQILNSDPSKSSFWEKKIKTTLngRGGEKYVLLR 81
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 741922299 181 LIRLVGIMLLLYVKQEHAAYISEVEAETVGTGIMGRMGNKGGVAIRFQFHNTSICVVNSHLAAHTEEYERRNQDYKDICS 260
Cdd:cd09090   82 SEQLVGTALLFFVKESQLPKVKNVEGSTKKTGLGGMSGNKGAVAIRFDYGDTSFCFVTSHLAAGLTNYEERNNDYKTIAR 161
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 741922299 261 RMQFCQvdpslpPLTISKHDVILWLGDLNYRIEDPDvEKVKKLIEEKAFQTLYAYDQLRAQVAAKAVFEGFSEGELTFQP 340
Cdd:cd09090  162 GLRFSR------GRTIKDHDHVIWLGDFNYRISLTN-EDVRRFILNGKLDKLLEYDQLNQQMNAGEVFPGFSEGPITFPP 234
                        250       260       270       280       290
                 ....*....|....*....|....*....|....*....|....*....|....*.
gi 741922299 341 TYKYDTGSDDWDTSEKCRAPAWCDRVLWKGKNITQLSYQSHMaLKTSDHKPVSSVF 396
Cdd:cd09090  235 TYKYDKGTDNYDTSEKQRIPAWTDRILYRGENLRQLSYNSAP-LRFSDHRPVYATF 289
INPP5c_INPP5J-like cd09094
Catalytic inositol polyphosphate 5-phosphatase (INPP5c) domain of inositol polyphosphate ...
105-398 1.85e-92

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


Pssm-ID: 197328  Cd Length: 300  Bit Score: 291.20  E-value: 1.85e-92
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 741922299 105 FRFFVGTYNVNGQSPKECLRPWLSHDTQ--APDVYCVGFQELDlSKEAFFFHDTPKEEEWFKAVSEALHPDaKYAKVKLI 182
Cdd:cd09094    1 LRVYVVTWNVATAPPPIDVRSLLGLQSPevAPDIYIIGLQEVN-SKPVQFVSDLIFDDPWSDLFMDILSPK-GYVKVSSI 78
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 741922299 183 RLVGIMLLLYVKQEHAAYISEVEAETVGTGIMGRMGNKGGVAIRFQFHNTSICVVNSHLAAHTEEYERRNQDYKDICSRm 262
Cdd:cd09094   79 RLQGLLLLVFVKIQHLPFIRDVQTNYTRTGLGGYWGNKGAVTVRFSLYGHMICFLNCHLPAHMEKWEQRIDDFETILST- 157
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 741922299 263 qfcQVDPSLPPLTISKHDVILWLGDLNYRIEDPDVEKVKKLIEEKAFQTLYAYDQLRAQVAAKAVFEGFSEGELTFQPTY 342
Cdd:cd09094  158 ---QVFNECNTPSILDHDYVFWFGDLNFRIEDVSIEFVRELVNSKKYHLLLEKDQLNMAKRKEEAFQGFQEGPLNFAPTY 234
                        250       260       270       280       290       300
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 741922299 343 KYDTGSDDWDTSEKCRAPAWCDRVLWKGK----------NITQLSYQSHMALKTSDHKPVSSVFDI 398
Cdd:cd09094  235 KFDLGTDEYDTSGKKRKPAWTDRILWKVNpdasteekflSITQTSYKSHMEYGISDHKPVTAQFRL 300
INPP5c_Synj cd09089
Catalytic inositol polyphosphate 5-phosphatase (INPP5c) domain of synaptojanins; This ...
106-398 2.24e-91

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


Pssm-ID: 197323 [Multi-domain]  Cd Length: 328  Bit Score: 289.29  E-value: 2.24e-91
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 741922299 106 RFFVGTYNVNGQS-------PKECLRPWLSH--------------DTQAPDVYCVGFQEL-DLSKEAFFFHDTPKEEEWF 163
Cdd:cd09089    2 RVFVGTWNVNGGKhfrsiafKHQSMTDWLLDnpklagqcsndseeDEKPVDIFAIGFEEMvDLNASNIVSASTTNQKEWG 81
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 741922299 164 KAVSEALHPDAKYAKVKLIRLVGIMLLLYVKQEHAAYISEVEAETVGTGIMGRMGNKGGVAIRFQFHNTSICVVNSHLAA 243
Cdd:cd09089   82 EELQKTISRDHKYVLLTSEQLVGVCLFVFVRPQHAPFIRDVAVDTVKTGLGGAAGNKGAVAIRFLLHSTSLCFVCSHFAA 161
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 741922299 244 HTEEYERRNQDYKDICSRMQFcqvdpslpPL--TISKHDVILWLGDLNYRIEDPDvEKVKKLIEEKAFQTLYAYDQLRAQ 321
Cdd:cd09089  162 GQSQVKERNEDFAEIARKLSF--------PMgrTLDSHDYVFWCGDFNYRIDLPN-DEVKELVRNGDWLKLLEFDQLTKQ 232
                        250       260       270       280       290       300       310       320
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 741922299 322 VAAKAVFEGFSEGELTFQPTYKYDTGSDDWDTSEKCRAPAWCDRVLWKGK-------------------NITQLSYQSHM 382
Cdd:cd09089  233 KAAGNVFKGFLEGEINFAPTYKYDLFSDDYDTSEKCRTPAWTDRVLWRRRkwpsdkteeslvetndptwNPGTLLYYGRA 312
                        330
                 ....*....|....*.
gi 741922299 383 ALKTSDHKPVSSVFDI 398
Cdd:cd09089  313 ELKTSDHRPVVAIIDI 328
RhoGAP_OCRL1 cd04380
RhoGAP_OCRL1: RhoGAP (GTPase-activator protein [GAP] for Rho-like small GTPases) domain ...
532-749 1.33e-82

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: 262.28  E-value: 1.33e-82
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 741922299 532 FLSVSGNYIPSCFGSPIHTLCYMKEPILDLPLEtireltlmQLQTEDNGSQLEKPMDIPKELWILVDYLYRNAIQQEDLF 611
Cdd:cd04380    1 FITVTGVYLPSCFGSSLETLIRLPDPGIRNLID--------QLELGDNPDYSEVPLSIPKEIWRLVDYLYTRGLAQEGLF 72
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 741922299 612 QQPGLRSEFDH----IRDCLDTGMIDNLSASNHSVAEALLLFLESLPEPVICYSAYRNCLECSGNLA-ASKQVI-TALPA 685
Cdd:cd04380   73 EEPGLPSEPGEllaeIRDALDTGSPFNSPGSAESVAEALLLFLESLPDPIIPYSLYERLLEAVANNEeDKRQVIrISLPP 152
                        170       180       190       200       210       220
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 741922299 686 CHRNVFTYLMAFLQELLKNSAKNHLDDNILASIFGSLLLRNPAGHQ-KLEMAEKKKAQEFVHQFL 749
Cdd:cd04380  153 VHRNVFVYLCSFLRELLSESADRGLDENTLATIFGRVLLRDPPRAGgKERRAERDRKRAFIEQFL 217
COG5411 COG5411
Phosphatidylinositol 5-phosphate phosphatase [Signal transduction mechanisms];
92-406 3.07e-72

Phosphatidylinositol 5-phosphate phosphatase [Signal transduction mechanisms];


Pssm-ID: 227698 [Multi-domain]  Cd Length: 460  Bit Score: 243.15  E-value: 3.07e-72
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 741922299  92 LIQKEEDYTYIQNFRFFVGTYNVNGQSPKECLRPWLSHD---TQAPDVYCVGFQE-LDLSKEAFFFHDT-----PKEEEW 162
Cdd:COG5411   17 LRQRRSKYVIEKDVSIFVSTFNPPGKPPKASTKRWLFPEieaTELADLYVVGLQEvVELTPGSILSADPydrlrIWESKV 96
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 741922299 163 FKAVSEALHpDAKYAKVKLIRLVGIMLLLYVKQEHAAYISEVEAETVGTGIMGRMGNKGGVAIRFQFHNTSICVVNSHLA 242
Cdd:COG5411   97 LDCLNGAQS-DEKYSLLRSPQLGGILLRVFSLATNLPVVKPVSGTVKKTGFGGSSSNKGAVAIRFNYERTSFCFVNSHLA 175
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 741922299 243 AHTEEYERRNQDYKDICSrmqfCQVDPSlpPLTISKHDVILWLGDLNYRIeDPDVEKVKKLIE--EKAFQTLYAYDQLRA 320
Cdd:COG5411  176 AGVNNIEERIFDYRSIAS----NICFSR--GLRIYDHDTIFWLGDLNYRV-TSTNEEVRPEIAsdDGRLDKLFEYDQLLW 248
                        250       260       270       280       290       300       310       320
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 741922299 321 QVAAKAVFEGFSEGELTFQPTYKYDTGSDDWDTSEKCRAPAWCDRVLWKGKNITQLSYQSHMALKTSDHKPVSSVFDIGV 400
Cdd:COG5411  249 EMEVGNVFPGFKEPVITFPPTYKFDYGTDEYDTSDKGRIPSWTDRILYKSEQLTPHSYSSIPHLMISDHRPVYATFRAKI 328

                 ....*.
gi 741922299 401 RVINEE 406
Cdd:COG5411  329 KVVDPS 334
INPP5c_Synj1 cd09098
Catalytic inositol polyphosphate 5-phosphatase (INPP5c) domain of synaptojanin 1; This ...
106-398 1.66e-70

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: 234.55  E-value: 1.66e-70
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 741922299 106 RFFVGTYNVNG-------------------QSPKECLRPWLSHDTQAP-DVYCVGFQEL-DLSKEAFFFHDTPKEEEWFK 164
Cdd:cd09098    2 RVCVGTWNVNGgkqfrsiafknqtltdwllDAPKKAGIPEFQDVRSKPvDIFAIGFEEMvELNAGNIVSASTTNQKLWAA 81
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 741922299 165 AVSEALHPDAKYAKVKLIRLVGIMLLLYVKQEHAAYISEVEAETVGTGIMGRMGNKGGVAIRFQFHNTSICVVNSHLAAH 244
Cdd:cd09098   82 ELQKTISRDQKYVLLASEQLVGVCLFVFIRPQHAPFIRDVAVDTVKTGMGGATGNKGAVAIRMLFHTTSLCFVCSHFAAG 161
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 741922299 245 TEEYERRNQDYKDICSRMQFcqvdpslpPL--TISKHDVILWLGDLNYRIEDPDvEKVKKLIEEKAFQTLYAYDQLRAQV 322
Cdd:cd09098  162 QSQVKERNEDFIEIARKLSF--------PMgrMLFSHDYVFWCGDFNYRIDIPN-EEVKELIRQQNWDSLIAGDQLINQK 232
                        250       260       270       280       290       300       310       320
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 741922299 323 AAKAVFEGFSEGELTFQPTYKYDTGSDDWDTSEKCRAPAWCDRVLWKGK----------------------------NIT 374
Cdd:cd09098  233 NAGQVFRGFLEGKLDFAPTYKYDLFSDDYDTSEKCRTPAWTDRVLWRRRkwpfdrsaedldllnasfpdnskeqytwSPG 312
                        330       340
                 ....*....|....*....|....
gi 741922299 375 QLSYQSHMALKTSDHKPVSSVFDI 398
Cdd:cd09098  313 TLLHYGRAELKTSDHRPVVALIDI 336
INPP5c_Synj2 cd09099
Catalytic inositol polyphosphate 5-phosphatase (INPP5c) domain of synaptojanin 2; This ...
106-398 1.39e-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: 221.05  E-value: 1.39e-65
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 741922299 106 RFFVGTYNVNG-------------------QSPKECLRPWLSHDTQAP-DVYCVGFQEL-DLSKEAFFFHDTPKEEEWFK 164
Cdd:cd09099    2 RVAMGTWNVNGgkqfrsnilgtseltdwllDSPKLSGTPDFQDDESNPpDIFAVGFEEMvELSAGNIVNASTTNRKMWGE 81
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 741922299 165 AVSEALHPDAKYAKVKLIRLVGIMLLLYVKQEHAAYISEVEAETVGTGIMGRMGNKGGVAIRFQFHNTSICVVNSHLAAH 244
Cdd:cd09099   82 QLQKAISRSHRYILLTSAQLVGVCLFIFVRPYHVPFIRDVAIDTVKTGMGGKAGNKGAVAIRFQFYSTSFCFICSHLTAG 161
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 741922299 245 TEEYERRNQDYKDICSRMQFcqvdpslpPL--TISKHDVILWLGDLNYRIEDPdVEKVKKLIEEKAFQTLYAYDQLRAQV 322
Cdd:cd09099  162 QNQVKERNEDYKEITQKLSF--------PMgrNVFSHDYVFWCGDFNYRIDLT-YEEVFYFIKRQDWKKLLEFDQLQLQK 232
                        250       260       270       280       290       300       310       320
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 741922299 323 AAKAVFEGFSEGELTFQPTYKYDTGSDDWDTSEKCRAPAWCDRVLWKGK----------------------NITQ----- 375
Cdd:cd09099  233 SSGKIFKDFHEGTINFGPTYKYDVGSEAYDTSDKCRTPAWTDRVLWWRKkwpfektageinlldsdldfdtKIRHtwtpg 312
                        330       340
                 ....*....|....*....|....
gi 741922299 376 -LSYQSHMALKTSDHKPVSSVFDI 398
Cdd:cd09099  313 aLMYYGRAELQASDHRPVLAIVEV 336
INPP5c_INPP5E-like cd09095
Catalytic inositol polyphosphate 5-phosphatase (INPP5c) domain of Inositol ...
103-398 7.32e-58

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: 198.80  E-value: 7.32e-58
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 741922299 103 QNFRFFVGTYNVNGQ-SPKECLRPWL--SHDTQAPDVYCVGFQEldlskeafffhDTPKEEEWFKAVSEALHPdaKYAKV 179
Cdd:cd09095    3 RNVGIFVATWNMQGQkELPENLDDFLlpTSADFAQDIYVIGVQE-----------GCSDRREWEIRLQETLGP--SHVLL 69
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 741922299 180 KLIRLVGIMLLLYVKQEHAAYISEVEAETVGTGIMGRMGNKGGVAIRFQFHNTSICVVNSHLAAHTEEYERRNQDYKDIC 259
Cdd:cd09095   70 HSASHGVLHLAVFIRRDLIWFCSEVESATVTTRIVSQIKTKGALAISFTFFGTSFLFITSHFTSGDGKVKERVLDYNKII 149
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 741922299 260 SRMQFCQVDPSLP-------PLTisKHDVILWLGDLNYRIEDPDvEKVKKLIEEKAFQT---LYAYDQLRAQVAAKAVFE 329
Cdd:cd09095  150 QALNLPRNVPTNPyksesgdVTT--RFDEVFWFGDFNFRLSGPR-HLVDALINQGQEVDvsaLLQHDQLTREMSKGSIFK 226
                        250       260       270       280       290       300       310
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|..
gi 741922299 330 GFSEGELTFQPTYKYDTGSDDWDTSEKCRAPAWCDRVLWKGK---NITQLSYQSHMALKTSDHKPVSSVFDI 398
Cdd:cd09095  227 GFQEAPIHFPPTYKFDIGSDVYDTSSKQRVPSYTDRILYRSRqkgDVCCLKYNSCPSIKTSDHRPVFALFRV 298
PLN03191 PLN03191
Type I inositol-1,4,5-trisphosphate 5-phosphatase 2; Provisional
153-412 3.29e-57

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


Pssm-ID: 215624 [Multi-domain]  Cd Length: 621  Bit Score: 206.30  E-value: 3.29e-57
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 741922299 153 FHDTPKEEEWFKAVSEALHPDAKYAKVKLIRLVGIMLLLYVKQEHAAYISEVEAETVGTGIMGRMGNKGGVAIRFQFHNT 232
Cdd:PLN03191 341 FKEVPSYQLPEDLIKDCRKVKQKYVRIVSKQMVGIYVSVWVRKRLRRHINNLKVSPVGVGLMGYMGNKGSVSISMSLFQS 420
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 741922299 233 SICVVNSHLAA-HTEEYE-RRNQDYKDICSRMQFCQVDPSLPPLTISKHDVILWLGDLNYRIEDPDVEkVKKLIEEKAFQ 310
Cdd:PLN03191 421 RLCFVCSHLTSgHKDGAEqRRNADVYEIIRRTRFSSVLDTDQPQTIPSHDQIFWFGDLNYRLNMLDTE-VRKLVAQKRWD 499
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 741922299 311 TLYAYDQLRAQVAAKAVFEGFSEGELTFQPTYKYDTGSDDW-----DTSEKCRAPAWCDRVLWKGKNITQLSYQsHMALK 385
Cdd:PLN03191 500 ELINSDQLIKELRSGHVFDGWKEGPIKFPPTYKYEINSDRYvgenpKEGEKKRSPAWCDRILWLGKGIKQLCYK-RSEIR 578
                        250       260
                 ....*....|....*....|....*..
gi 741922299 386 TSDHKPVSSVFDIGVRVINEELYRKTL 412
Cdd:PLN03191 579 LSDHRPVSSMFLVEVEVFDHRKLQRAL 605
INPP5c_SHIP cd09091
Catalytic inositol polyphosphate 5-phosphatase (INPP5c) domain of SH2 domain containing ...
108-398 1.03e-52

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


Pssm-ID: 197325  Cd Length: 307  Bit Score: 185.15  E-value: 1.03e-52
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 741922299 108 FVGTYNVNGQSPKECLRPWL-----------SHDTQAPDVYCVGFQEldlskeafffhDTPKEEEWFKAVSEALH--PDA 174
Cdd:cd09091    4 FIGTWNMGSAPPPKNITSWFtskgqgktrddVADYIPHDIYVIGTQE-----------DPLGEKEWLDLLRHSLKelTSL 72
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 741922299 175 KYAKVKLIRLVGIMLLLYVKQEHAAYISEVEAETVGTGIMGRMGNKGGVAIRFQFHNTSICVVNSHLAAHTEEYERRNQD 254
Cdd:cd09091   73 DYKPIAMQTLWNIRIVVLAKPEHENRISHVCTSSVKTGIANTLGNKGAVGVSFMFNGTSFGFVNSHLTSGSEKKLRRNQN 152
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 741922299 255 YKDIcsrMQFCQV-DPSLPPLTIS-KHDVILWLGDLNYRIEDP--DVEKVKKLIEEKAFQTLYAYDQLRAQVAAKAVFEG 330
Cdd:cd09091  153 YLNI---LRFLSLgDKKLSAFNIThRFTHLFWLGDLNYRLDLPiqEAENIIQKIEQQQFEPLLRHDQLNLEREEHKVFLR 229
                        250       260       270       280       290       300       310
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 741922299 331 FSEGELTFQPTYKYDTGSDD---WD----TSEKCRAPAWCDRVLWKGKNITQL---SYQSHMALKTSDHKPVSSVFDI 398
Cdd:cd09091  230 FSEEEITFPPTYRYERGSRDtyaYTkqkaTGVKYNLPSWCDRILWKSYPETHIicqSYGCTDDIVTSDHSPVFGTFEV 307
INPP5c_SHIP1-INPP5D cd09100
Catalytic inositol polyphosphate 5-phosphatase (INPP5c) domain of SH2 domain containing ...
108-398 1.26e-52

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


Pssm-ID: 197334  Cd Length: 307  Bit Score: 184.80  E-value: 1.26e-52
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 741922299 108 FVGTYNVNGQSPKECLRPWLSHDTQAP-----------DVYCVGFQEldlskeafffhDTPKEEEWFKAVSEALH--PDA 174
Cdd:cd09100    4 FIGTWNMGNAPPPKKITSWFQCKGQGKtrddtadyiphDIYVIGTQE-----------DPLGEKEWLDTLKHSLReiTSI 72
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 741922299 175 KYAKVKLIRLVGIMLLLYVKQEHAAYISEVEAETVGTGIMGRMGNKGGVAIRFQFHNTSICVVNSHLAAHTEEYERRNQD 254
Cdd:cd09100   73 SFKVIAIQTLWNIRIVVLAKPEHENRISHICTDSVKTGIANTLGNKGAVGVSFMFNGTSFGFVNSHLTSGSEKKLRRNQN 152
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 741922299 255 YKDIcsrMQFCQV-DPSLPPLTIS-KHDVILWLGDLNYRIEDP--DVEKVKKLIEEKAFQTLYAYDQLRAQVAAKAVFEG 330
Cdd:cd09100  153 YFNI---LRFLVLgDKKLSPFNIThRFTHLFWLGDLNYRVELPntEAENIIQKIKQQQYQELLPHDQLLIERKESKVFLQ 229
                        250       260       270       280       290       300       310
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 741922299 331 FSEGELTFQPTYKYDTGSDDWDTSEKCRA-------PAWCDRVLWKGKNITQL---SYQSHMALKTSDHKPVSSVFDI 398
Cdd:cd09100  230 FEEEEITFAPTYRFERGTRERYAYTKQKAtgmkynlPSWCDRVLWKSYPLVHVvcqSYGCTDDITTSDHSPVFATFEV 307
INPP5c_SHIP2-INPPL1 cd09101
Catalytic inositol polyphosphate 5-phosphatase (INPP5c) domain of SH2 domain containing ...
108-398 5.40e-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: 177.47  E-value: 5.40e-50
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 741922299 108 FVGTYNVNGQSPKECLRPWLSHD-----------TQAPDVYCVGFQELDLSkeafffhdtpkEEEWFKAVSEALHP--DA 174
Cdd:cd09101    4 FIGTWNMGSVPPPKSLASWLTSRglgktldettvTIPHDIYVFGTQENSVG-----------DREWVDFLRASLKEltDI 72
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 741922299 175 KYAKVKLIRLVGIMLLLYVKQEHAAYISEVEAETVGTGIMGRMGNKGGVAIRFQFHNTSICVVNSHLAAHTEEYERRNQD 254
Cdd:cd09101   73 DYQPIALQCLWNIKMVVLVKPEHENRISHVHTSSVKTGIANTLGNKGAVGVSFMFNGTSFGFVNCHLTSGNEKTHRRNQN 152
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 741922299 255 YKDICSRMQFCqvDPSLPPLTIS-KHDVILWLGDLNYRIeDPDVEKVKKLIEEKAFQTLYAYDQLRAQVAAKAVFEGFSE 333
Cdd:cd09101  153 YLDILRSLSLG--DKQLNAFDISlRFTHLFWFGDLNYRL-DMDIQEILNYITRKEFDPLLAVDQLNLEREKNKVFLRFRE 229
                        250       260       270       280       290       300       310
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 741922299 334 GELTFQPTYKYDTGSDD---WD----TSEKCRAPAWCDRVLWKGKNITQL---SYQSHMALKTSDHKPVSSVFDI 398
Cdd:cd09101  230 EEISFPPTYRYERGSRDtymWQkqktTGMRTNVPSWCDRILWKSYPETHIvcnSYGCTDDIVTSDHSPVFGTFEV 304
RhoGAP smart00324
GTPase-activator protein for Rho-like GTPases; GTPase activator proteins towards Rho/Rac ...
588-752 1.01e-39

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


Pssm-ID: 214618  Cd Length: 174  Bit Score: 144.33  E-value: 1.01e-39
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 741922299   588 DIPKELWILVDYLYRNAIQQEDLFQQPGLRSEFDHIRDCLDTGMIDNL---SASNHSVAEALLLFLESLPEPVICYSAYR 664
Cdd:smart00324   2 PIPIIVEKCIEYLEKRGLDTEGIYRVSGSKSRVKELRDAFDSGPDPDLdlsEYDVHDVAGLLKLFLRELPEPLITYELYE 81
                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 741922299   665 NCLECSGN------LAASKQVITALPACHRNVFTYLMAFLQELLKNSAKNHLDDNILASIFGSLLLRNPAGHQKLEMaEK 738
Cdd:smart00324  82 EFIEAAKLedeterLRALRELLSLLPPANRATLRYLLAHLNRVAEHSEENKMTARNLAIVFGPTLLRPPDGEVASLK-DI 160
                          170
                   ....*....|....
gi 741922299   739 KKAQEFVHQFLTHP 752
Cdd:smart00324 161 RHQNTVIEFLIENA 174
RhoGAP pfam00620
RhoGAP domain; GTPase activator proteins towards Rho/Rac/Cdc42-like small GTPases.
590-728 9.21e-36

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


Pssm-ID: 459875  Cd Length: 148  Bit Score: 132.28  E-value: 9.21e-36
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 741922299  590 PKELWILVDYLYRNAIQQEDLFQQPGLRSEFDHIRDCLDTG---MIDNLSASNHSVAEALLLFLESLPEPVICYSAYRNC 666
Cdd:pfam00620   1 PLIVRKCVEYLEKRGLDTEGIFRVSGSASRIKELREAFDRGpdvDLDLEEEDVHVVASLLKLFLRELPEPLLTFELYEEF 80
                          90       100       110       120       130       140
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 741922299  667 LEC------SGNLAASKQVITALPACHRNVFTYLMAFLQELLKNSAKNHLDDNILASIFGSLLLRNPA 728
Cdd:pfam00620  81 IEAaklpdeEERLEALRELLRKLPPANRDTLRYLLAHLNRVAQNSDVNKMNAHNLAIVFGPTLLRPPD 148
RhoGAP cd00159
RhoGAP: GTPase-activator protein (GAP) for Rho-like GTPases; GAPs towards Rho/Rac/Cdc42-like ...
590-751 6.86e-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: 107.39  E-value: 6.86e-27
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 741922299 590 PKELWILVDYLYRNAIQQEDLFQQPGLRSEFDHIRDCLDTGM-IDNLSASN-HSVAEALLLFLESLPEPVICYSAYRNCL 667
Cdd:cd00159    1 PLIIEKCIEYLEKNGLNTEGIFRVSGSASKIEELKKKFDRGEdIDDLEDYDvHDVASLLKLYLRELPEPLIPFELYDEFI 80
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 741922299 668 ECSGN------LAASKQVITALPACHRNVFTYLMAFLQELLKNSAKNHLDDNILASIFGSLLLRNPAGHQKlEMAEKKKA 741
Cdd:cd00159   81 ELAKIedeeerIEALKELLKSLPPENRDLLKYLLKLLHKISQNSEVNKMTASNLAIVFAPTLLRPPDSDDE-LLEDIKKL 159
                        170
                 ....*....|
gi 741922299 742 QEFVHQFLTH 751
Cdd:cd00159  160 NEIVEFLIEN 169
RhoGAP_FAM13A1a cd04393
RhoGAP_FAM13A1a: RhoGAP (GTPase-activator protein [GAP] for Rho-like small GTPases) domain of ...
557-751 2.43e-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: 77.89  E-value: 2.43e-16
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 741922299 557 PILDLPLETIRELTLMqlqteDNGsqlekpmdIPKELWILVDYLYRNAIQQEDLFQQPGLRSEFDHIRDCLDTGMIDNLS 636
Cdd:cd04393    1 KVFGVPLQELQQAGQP-----ENG--------VPAVVRHIVEYLEQHGLEQEGLFRVNGNAETVEWLRQRLDSGEEVDLS 67
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 741922299 637 --ASNHSVAEALLLFLESLPEPVI----------CYSAYRNCLEcsgNLAASKQVITALPACHRNVFTYLMAFLQELLKN 704
Cdd:cd04393   68 keADVCSAASLLRLFLQELPEGLIpaslqirlmqLYQDYNGEDE---FGRKLRDLLQQLPPVNYSLLKFLCHFLSNVASQ 144
                        170       180       190       200
                 ....*....|....*....|....*....|....*....|....*..
gi 741922299 705 SAKNHLDDNILASIFGSLLLRNPAGhqklemAEKKKAQEFVHQFLTH 751
Cdd:cd04393  145 HHENRMTAENLAAVFGPDVFHVYTD------VEDMKEQEICSRIMAK 185
RhoGAP_KIAA1688 cd04389
RhoGAP_KIAA1688: GTPase-activator protein (GAP) domain for Rho-like GTPases found in ...
580-751 9.85e-15

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: 73.19  E-value: 9.85e-15
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 741922299 580 GSQLEKPMDIPKEL-------WILV----DYLYRNAIQQEDLFQQPGLRSEFDHIRDCLDTGMIDNLSASN-HSVAEALL 647
Cdd:cd04389    2 GSSLEEIMDRQKEKypelklpWILTflseKVLALGGFQTEGIFRVPGDIDEVNELKLRVDQWDYPLSGLEDpHVPASLLK 81
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 741922299 648 LFLESLPEPVICYSAYRNCLECSGNLAASKQVITALPACHRNVFTYLMAFLQELLK--NSAKNHLDDNILASIFGSLLLR 725
Cdd:cd04389   82 LWLRELEEPLIPDALYQQCISASEDPDKAVEIVQKLPIINRLVLCYLINFLQVFAQpeNVAHTKMDVSNLAMVFAPNILR 161
                        170       180
                 ....*....|....*....|....*.
gi 741922299 726 NPAGHQKLEMAEKKKAQEFVHQFLTH 751
Cdd:cd04389  162 CTSDDPRVIFENTRKEMSFLRTLIEH 187
RhoGAP_ARHGAP22_24_25 cd04390
RhoGAP_ARHGAP22_24_25: GTPase-activator protein (GAP) domain for Rho-like GTPases found in ...
597-725 2.37e-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: 2.37e-13
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 741922299 597 VDYLYRNAIQQEDLFQQPGLRSEFDHIRDCLDTGMIDNLSASN--HSVAEALLLFLESLPEPVICYSAYRNCLECSGNLA 674
Cdd:cd04390   30 VDFIREHGLKEEGLFRLPGQANLVKQLQDAFDAGERPSFDSDTdvHTVASLLKLYLRELPEPVIPWAQYEDFLSCAQLLS 109
                         90       100       110       120       130
                 ....*....|....*....|....*....|....*....|....*....|....*....
gi 741922299 675 AS--------KQVITALPACHRNVFTYLMAFLQELLKNSAKNHLDDNILASIFGSLLLR 725
Cdd:cd04390  110 KDeekglgelMKQVSILPKVNYNLLSYICRFLDEVQSNSSVNKMSVQNLATVFGPNILR 168
RhoGAP-p50rhoGAP cd04404
RhoGAP-p50rhoGAP: RhoGAP (GTPase-activator protein [GAP] for Rho-like small GTPases) domain of ...
589-727 8.67e-11

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: 61.97  E-value: 8.67e-11
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 741922299 589 IPKELWILVDYLYRNAIQQEDLFQQPGLRSEFDHIRDCLDTGMIDNLSASNHSVAEALLL--FLESLPEPVICYSAYRNC 666
Cdd:cd04404   23 IPPVVRETVEYLQAHALTTEGIFRRSANTQVVKEVQQKYNMGEPVDFDQYEDVHLPAVILktFLRELPEPLLTFDLYDDI 102
                         90       100       110       120       130       140
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 741922299 667 -----LECSGNLAASKQVITALPACHRNVFTYLMAFLQELLKNSAKNHLDDNILASIFGSLLLRNP 727
Cdd:cd04404  103 vgflnVDKEERVERVKQLLQTLPEENYQVLKYLIKFLVQVSAHSDQNKMTNSNLAVVFGPNLLWAK 168
RhoGAP_nadrin cd04386
RhoGAP_nadrin: RhoGAP (GTPase-activator protein [GAP] for Rho-like small GTPases) domain of ...
597-736 1.84e-10

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: 60.93  E-value: 1.84e-10
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 741922299 597 VDYLYRNAIQQEDLFQQPGLRSEFDHIRDCLDTGMIDNLSASN----HSVAEALLLFLESLPEPVICYSAYRNCLECSG- 671
Cdd:cd04386   28 VMCLLETGMNEEGLFRVGGGASKLKRLKAALDAGTFSLPLDEFysdpHAVASALKSYLRELPDPLLTYNLYEDWVQAANk 107
                         90       100       110       120       130       140       150
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 741922299 672 -----NLAASKQVITALPACHRNVFTYLMAFLQELLKNSAKNHLDDNILASIFGSLLLRNPAGHQKLEMA 736
Cdd:cd04386  108 pdedeRLQAIWRILNKLPRENRDNLRYLIKFLSKLAQKSDENKMSPSNIAIVLAPNLLWAKNEGSLAEMA 177
RhoGAP_srGAP cd04383
RhoGAP_srGAP: RhoGAP (GTPase-activator protein [GAP] for Rho-like small GTPases) domain ...
579-734 5.35e-10

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: 59.36  E-value: 5.35e-10
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 741922299 579 NGSQLEKPMDIPKELWILVD----YLYRNAIQQEDLFQQPGLRSEFDHIRDCLDTG---MIDNLSASN-HSVAEALLLFL 650
Cdd:cd04383    4 NGSLEEYIQDSGQAIPLVVEscirFINLYGLQHQGIFRVSGSQVEVNDIKNAFERGedpLADDQNDHDiNSVAGVLKLYF 83
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 741922299 651 ESLPEPVICYSAYRNCLEC--SGNLAAS----KQVITALPACHRNVFTYLMAFLQELLKNSAKNHLDDNILASIFGSLLL 724
Cdd:cd04383   84 RGLENPLFPKERFEDLMSCvkLENPTERvhqiREILSTLPRSVIIVMRYLFAFLNHLSQFSDENMMDPYNLAICFGPTLM 163
                        170
                 ....*....|
gi 741922299 725 RNPAGHQKLE 734
Cdd:cd04383  164 PVPEGQDQVS 173
EEP cd08372
Exonuclease-Endonuclease-Phosphatase (EEP) domain superfamily; This large superfamily includes ...
109-392 8.47e-10

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: 59.80  E-value: 8.47e-10
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 741922299 109 VGTYNVNGQSPKECLRPWLSHD-TQAPDVycVGFQELDLSKEAFFFHDTPKEEEWFKAVSEALHPDaKYAKVklirlvgi 187
Cdd:cd08372    1 VASYNVNGLNAATRASGIARWVrELDPDI--VCLQEVKDSQYSAVALNQLLPEGYHQYQSGPSRKE-GYEGV-------- 69
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 741922299 188 mlLLYVKQEHAAyISEVeaeTVGTGIMGRMGNKGGVAIRFQFHNTSICVVNSHLAAHTEEYERRNQDYKDICSRMQFCQV 267
Cdd:cd08372   70 --AILSKTPKFK-IVEK---HQYKFGEGDSGERRAVVVKFDVHDKELCVVNAHLQAGGTRADVRDAQLKEVLEFLKRLRQ 143
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 741922299 268 DPSLPpltiskhdvILWLGDLNYRIEDPDVEKVKKLIEekafqtlyaydqLRAQVAAKAVFEgfsegELTFQPTykydtg 347
Cdd:cd08372  144 PNSAP---------VVICGDFNVRPSEVDSENPSSMLR------------LFVALNLVDSFE-----TLPHAYT------ 191
                        250       260       270       280       290
                 ....*....|....*....|....*....|....*....|....*....|...
gi 741922299 348 sddWDTSEKcRAPAWCDRVLW--------KGKNITQLSYQSHMAlktSDHKPV 392
Cdd:cd08372  192 ---FDTYMH-NVKSRLDYIFVsksllpsvKSSKILSDAARARIP---SDHYPI 237
RhoGAP_chimaerin cd04372
RhoGAP_chimaerin: RhoGAP (GTPase-activator protein [GAP] for Rho-like small GTPases) domain of ...
605-755 3.46e-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: 57.14  E-value: 3.46e-09
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 741922299 605 IQQEDLFQQPGLRSEFDHIRDCLD-TGMIDNLSASNHS----VAEALLLFLESLPEPVICYSAYRNCLECS--GN----L 673
Cdd:cd04372   32 LQSEGLYRVSGFAEEIEDVKMAFDrDGEKADISATVYPdinvITGALKLYFRDLPIPVITYDTYPKFIDAAkiSNpderL 111
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 741922299 674 AASKQVITALPACHRNVFTYLMAFLQELLKNSAKNHLDDNILASIFGSLLLRNPAGHQKLEMAEKKKAQEFVHQFLTHPE 753
Cdd:cd04372  112 EAVHEALMLLPPAHYETLRYLMEHLKRVTLHEKDNKMNAENLGIVFGPTLMRPPEDSALTTLNDMRYQILIVQLLITNED 191

                 ..
gi 741922299 754 PL 755
Cdd:cd04372  192 VL 193
RhoGAP_ARHGAP6 cd04376
RhoGAP_ARHGAP6: RhoGAP (GTPase-activator protein [GAP] for Rho-like small GTPases) domain of ...
616-747 3.53e-09

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: 57.45  E-value: 3.53e-09
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 741922299 616 LRSEFDHIrdcLDTGMIDNLSAsnHSVAEALLLFLESLPEPVIC---YSAYRNC--LECSGNLAASKQVITALPACHRNV 690
Cdd:cd04376   43 LREEFDRG---IDVVLDENHSV--HDVAALLKEFFRDMPDPLLPrelYTAFIGTalLEPDEQLEALQLLIYLLPPCNCDT 117
                         90       100       110       120       130       140
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 741922299 691 FTYLMAFLQELLKNSAKNH-----------LDDNILASIFGSLLLRNPAGHQKLEMAEKKKAQEFVHQ 747
Cdd:cd04376  118 LHRLLKFLHTVAEHAADSIdedgqevsgnkMTSLNLATIFGPNLLHKQKSGEREFVQASLRIEESTAI 185
RhoGAP-ARHGAP11A cd04394
RhoGAP-ARHGAP11A: RhoGAP (GTPase-activator protein [GAP] for Rho-like small GTPases) domain of ...
588-744 5.71e-09

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: 56.71  E-value: 5.71e-09
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 741922299 588 DIPKELWILVDYLYRNaIQQEDLFQQPG-------LRSEFDHIRDCLDTGMIDNlsasnhsVAEALLLFLESLPEPVICY 660
Cdd:cd04394   19 NVPKFLVDACTFLLDH-LSTEGLFRKSGsvvrqkeLKAKLEGGEACLSSALPCD-------VAGLLKQFFRELPEPLLPY 90
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 741922299 661 ---SAYRNCLECSGNLAASKQVITA---LPACHRNVFTYLMAFLQELLKNSAKNHLDDNILASIFGSLLLRNPAGHQKLE 734
Cdd:cd04394   91 dlhEALLKAQELPTDEERKSATLLLtclLPDEHVNTLRYFFSFLYDVAQRCSENKMDSSNLAVIFAPNLFQSEEGGEKMS 170
                        170
                 ....*....|
gi 741922299 735 MAEKKKAQEF 744
Cdd:cd04394  171 SSTEKRLRLQ 180
RhoGAP_ARHGAP20 cd04402
RhoGAP_ARHGAP20: RhoGAP (GTPase-activator protein [GAP] for Rho-like small GTPases) domain of ...
590-750 1.85e-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: 55.00  E-value: 1.85e-08
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 741922299 590 PKELWILVDYLYRNAIQQEDLFQQPGLRSEFDHIRDCLDTGMIDNLSASN-HSVAEALLLFLESLPEPVICYSAYRNCLE 668
Cdd:cd04402   16 PKPILDMLSLLYQKGPSTEGIFRRSANAKACKELKEKLNSGVEVDLKAEPvLLLASVLKDFLRNIPGSLLSSDLYEEWMS 95
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 741922299 669 C------SGNLAASKQVITALPACHRNVFTYLMAFLQELLKNSAKNHLDDNILASIFGSLLLRNPAGhQKLEMAEKKKAQ 742
Cdd:cd04402   96 AldqeneEEKIAELQRLLDKLPRPNVLLLKHLICVLHNISQNSETNKMDAFNLAVCIAPSLLWPPAS-SELQNEDLKKVT 174

                 ....*...
gi 741922299 743 EFVhQFLT 750
Cdd:cd04402  175 SLV-QFLI 181
RhoGAP_GMIP_PARG1 cd04378
RhoGAP_GMIP_PARG1: RhoGAP (GTPase-activator protein [GAP] for Rho-like small GTPases) domain ...
637-735 4.20e-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: 54.35  E-value: 4.20e-08
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 741922299 637 ASNHSVAEALLLFLESLPEPVICYSAYRN--------------------CLECSGNLAASKQVITALPACHRNVFTYLMA 696
Cdd:cd04378   66 LSPHDISSVLKLFLRQLPEPLILFRLYNDfialakeiqrdteedkapntPIEVNRIIRKLKDLLRQLPASNYNTLQHLIA 145
                         90       100       110
                 ....*....|....*....|....*....|....*....
gi 741922299 697 FLQELLKNSAKNHLDDNILASIFGSLLLRNPAGHQKLEM 735
Cdd:cd04378  146 HLYRVAEQFEENKMSPNNLGIVFGPTLIRPRPGDADVSL 184
RhoGAP_myosin_IX cd04377
RhoGAP_myosin_IX: RhoGAP (GTPase-activator protein [GAP] for Rho-like small GTPases) domain ...
589-727 7.82e-08

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


Pssm-ID: 239842  Cd Length: 186  Bit Score: 53.21  E-value: 7.82e-08
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 741922299 589 IPKELWILVDYLYRNAIQQEDLFQQPGLRSEFDHIRDCLDTGMiDNLSASN---HSVAEALLLFLESLPEPVICYSAYRN 665
Cdd:cd04377   15 VPLVLEKLLEHIEMHGLYTEGIYRKSGSANKIKELRQGLDTDP-DSVNLEDypiHVITSVLKQWLRELPEPLMTFELYEN 93
                         90       100       110       120       130       140
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 741922299 666 CLECSG------NLAASKQVITALPACHRNVFTYLMAFLQELLKNSAKNHLDDNILASIFGSLLLRNP 727
Cdd:cd04377   94 FLRAMEleekqeRVRALYSVLEQLPRANLNTLERLIFHLVRVALQEEVNRMSANALAIVFAPCILRCP 161
RhoGAP_fRGD1 cd04398
RhoGAP_fRGD1: RhoGAP (GTPase-activator protein [GAP] for Rho-like small GTPases) domain of ...
616-743 1.09e-07

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


Pssm-ID: 239863  Cd Length: 192  Bit Score: 52.79  E-value: 1.09e-07
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 741922299 616 LRSEFDHIRDCLDTGMIDNLSASNHSVAEALLLFLESLPEPVICYSAYRNCLECSGNLAASK------QVITALPACHRN 689
Cdd:cd04398   50 LKELFDKDPLNVLLISPEDYESDIHSVASLLKLFFRELPEPLLTKALSREFIEAAKIEDESRrrdalhGLINDLPDANYA 129
                         90       100       110       120       130
                 ....*....|....*....|....*....|....*....|....*....|....
gi 741922299 690 VFTYLMAFLQELLKNSAKNHLDDNILASIFGSLLLrNPAGHQKLEMAEKKKAQE 743
Cdd:cd04398  130 TLRALMFHLARIKEHESVNRMSVNNLAIIWGPTLM-NAAPDNAADMSFQSRVIE 182
RhoGAP_p190 cd04373
RhoGAP_p190: RhoGAP (GTPase-activator protein [GAP] for Rho-like small GTPases) domain of ...
584-725 3.26e-07

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: 51.30  E-value: 3.26e-07
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 741922299 584 EKPmdIPKELWILVDYLYRNAIQQEDLFQQPGLRSEFDHIRDCLDTGMIDNLSASN---HSVAEALLLFLESLPEPVICY 660
Cdd:cd04373   12 EKP--IPIFLEKCVEFIEATGLETEGIYRVSGNKTHLDSLQKQFDQDHNLDLVSKDftvNAVAGALKSFFSELPDPLIPY 89
                         90       100       110       120       130       140       150
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|.
gi 741922299 661 SAYRNCLECSG------NLAASKQVITALPACHRNVFTYLMAFLQELLKNSAKNHLDDNILASIFGSLLLR 725
Cdd:cd04373   90 SMHLELVEAAKindreqRLHALKELLKKFPPENFDVFKYVITHLNKVSQNSKVNLMTSENLSICFWPTLMR 160
RhoGAP_myosin_IXB cd04407
RhoGAP_myosin_IXB: RhoGAP (GTPase-activator protein [GAP] for Rho-like small GTPases) domain ...
589-727 8.83e-07

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: 49.99  E-value: 8.83e-07
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 741922299 589 IPKELWILVDYLYRNAIQQEDLFQQPGLRSEFDHIRDCLDTGMiDNLSASN---HSVAEALLLFLESLPEPVICYSAYRN 665
Cdd:cd04407   15 VPIVLEKLLEHVEMHGLYTEGIYRKSGSANRMKELHQLLQADP-ENVKLENypiHAITGLLKQWLRELPEPLMTFAQYND 93
                         90       100       110       120       130       140
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 741922299 666 CL------ECSGNLAASKQVITALPACHRNVFTYLMAFLQELLKNSAKNHLDDNILASIFGSLLLRNP 727
Cdd:cd04407   94 FLravelpEKQEQLQAIYRVLEQLPTANHNTLERLIFHLVKVALEEDVNRMSPNALAIVFAPCLLRCP 161
RhoGAP_CdGAP cd04384
RhoGAP_CdGAP: RhoGAP (GTPase-activator protein [GAP] for Rho-like small GTPases) domain of ...
610-728 1.24e-06

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


Pssm-ID: 239849 [Multi-domain]  Cd Length: 195  Bit Score: 49.81  E-value: 1.24e-06
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 741922299 610 LFQQPGLRSEFDHIRDCLDTGMIDNLSASN-----HSVAEALLLFLESLPEPVICYSAYRNCLEC------SGNLAASKQ 678
Cdd:cd04384   38 IYRLSGIASNIQRLRHEFDSEQIPDLTKDVyiqdiHSVSSLCKLYFRELPNPLLTYQLYEKFSEAvsaasdEERLEKIHD 117
                         90       100       110       120       130
                 ....*....|....*....|....*....|....*....|....*....|
gi 741922299 679 VITALPACHRNVFTYLMAFLQELLKNSAKNHLDDNILASIFGSLLLRNPA 728
Cdd:cd04384  118 VIQQLPPPHYRTLEFLMRHLSRLAKYCSITNMHAKNLAIVWAPNLLRSKQ 167
RhoGAP_p85 cd04388
RhoGAP_p85: RhoGAP (GTPase-activator protein [GAP] for Rho-like small GTPases) domain present ...
586-728 1.25e-06

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


Pssm-ID: 239853  Cd Length: 200  Bit Score: 49.87  E-value: 1.25e-06
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 741922299 586 PMDI-PKELWILVDYLYRNAIQQEDLF--QQPGLRSEFDHIRDClDTGMIDNLSASNHSVAEALLLFLESLPEPVICYSA 662
Cdd:cd04388   11 PPDVaPPLLIKLVEAIEKKGLESSTLYrtQSSSSLTELRQILDC-DAASVDLEQFDVAALADALKRYLLDLPNPVIPAPV 89
                         90       100       110       120       130       140       150
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 741922299 663 YRNCLECSGNLAASKQVI---------TALPACHRNVFTYLMAFLQELLKNSAKNHLDDNILASIFGSLLLRNPA 728
Cdd:cd04388   90 YSEMISRAQEVQSSDEYAqllrklirsPNLPHQYWLTLQYLLKHFFRLCQSSSKNLLSARALAEIFSPLLFRFQP 164
RhoGAP_GMIP cd04408
RhoGAP_GMIP: RhoGAP (GTPase-activator protein [GAP] for Rho-like small GTPases) domain of GMIP ...
638-729 3.56e-06

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: 48.27  E-value: 3.56e-06
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 741922299 638 SNHSVAEALLLFLESLPEPVICYSAYRNCLECSGNLAAS------------------KQVITALPACHRNVFTYLMAFLQ 699
Cdd:cd04408   67 SPHDITSVLKHFLKELPEPVLPFQLYDDFIALAKELQRDsekaaespsiveniirslKELLGRLPVSNYNTLRHLMAHLY 146
                         90       100       110
                 ....*....|....*....|....*....|
gi 741922299 700 ELLKNSAKNHLDDNILASIFGSLLLRNPAG 729
Cdd:cd04408  147 RVAERFEDNKMSPNNLGIVFGPTLLRPLVG 176
RhoGAP_fBEM3 cd04400
RhoGAP_fBEM3: RhoGAP (GTPase-activator [GAP] protein for Rho-like small GTPases) domain of ...
588-724 4.29e-06

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: 48.12  E-value: 4.29e-06
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 741922299 588 DIPKELWILVDYLY-RNAIQQEDLFQQPGLRSEFDHIRDCLDTGMIDNLSASN-----HSVAEALLLFLESLPEPVI--- 658
Cdd:cd04400   21 DLPSVVYRCIEYLDkNRAIYEEGIFRLSGSASVIKQLKERFNTEYDVDLFSSSlypdvHTVAGLLKLYLRELPTLILgge 100
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 741922299 659 CYSAYRNCLECSGN----LAASKQVITALPACHRNVFTYLMAFLQELLKNSAKNHLDD-----------NILASIFGSLL 723
Cdd:cd04400  101 LHNDFKRLVEENHDrsqrALELKDLVSQLPQANYDLLYVLFSFLRKIIEHSDVNKMNLrnvcivfsptlNIPAGIFVLFL 180

                 .
gi 741922299 724 L 724
Cdd:cd04400  181 T 181
RhoGAP_ARHGAP19 cd04392
RhoGAP_ARHGAP19: RhoGAP (GTPase-activator protein [GAP] for Rho-like small GTPases) domain of ...
596-724 4.55e-06

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: 48.23  E-value: 4.55e-06
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 741922299 596 LVDYLYRNaIQQEDLFQQPGLRSEFDHIRDCLDTGMIDNLSA---SNHSVAEALLLFLESLPEPVICYSAYRNCLECS-- 670
Cdd:cd04392   16 LIEYLEKN-LRVEGLFRKPGNSARQQELRDLLNSGTDLDLESggfHAHDCATVLKGFLGELPEPLLTHAHYPAHLQIAdl 94
                         90       100       110       120       130       140       150
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 741922299 671 ------GN----------LAASKQVITALPACHRNVFTYLMAFLQELLKNSAKNHLDDNILASIFGSLLL 724
Cdd:cd04392   95 cqfdekGNktsapdkerlLEALQLLLLLLPEENRNLLKLILDLLYQTAKHEDKNKMSADNLALLFTPHLI 164
RhoGAP_ARHGAP21 cd04395
RhoGAP_ARHGAP21: RhoGAP (GTPase-activator protein [GAP] for Rho-like small GTPases) domain of ...
640-727 4.69e-06

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


Pssm-ID: 239860  Cd Length: 196  Bit Score: 48.17  E-value: 4.69e-06
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 741922299 640 HSVAEALLLFLESLPEPVICYSAYRNCLEC------SGNLAASKQVITALPACHRNVFTYLMAFLQELLKNSAKNHLDDN 713
Cdd:cd04395   74 NVVSSLLKSFFRKLPEPLFTNELYPDFIEAnriedpVERLKELRRLIHSLPDHHYETLKHLIRHLKTVADNSEVNKMEPR 153
                         90
                 ....*....|....
gi 741922299 714 ILASIFGSLLLRNP 727
Cdd:cd04395  154 NLAIVFGPTLVRTS 167
RhoGAP_DLC1 cd04375
RhoGAP_DLC1: RhoGAP (GTPase-activator protein [GAP] for Rho-like small GTPases) domain of ...
589-751 7.35e-06

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: 47.80  E-value: 7.35e-06
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 741922299 589 IPKELWILVDYLYRNAIQQEDLFQQPGLRSEFDHIRDCL----DTGMIDNLSAsnHSVAEALLLFLESLPEPVI------ 658
Cdd:cd04375   20 LPRSIQQAMRWLRNNALDQVGLFRKSGVKSRIQKLRSMIesstDNVNYDGQQA--YDVADMLKQYFRDLPEPLLtnklse 97
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 741922299 659 CYSAYRNCLECSGNLAASKQVITALPACHRNVFTYLMAFLQELLKNSAKNHLDDNILA-----SIFGSLLLR----NPAG 729
Cdd:cd04375   98 TFIAIFQYVPKEQRLEAVQCAILLLPDENREVLQTLLYFLSDVAANSQENQMTATNLAvclapSLFHLNTSRrensSPAR 177
                        170       180       190
                 ....*....|....*....|....*....|..
gi 741922299 730 HQKL----------EMAEKKKAQEFVHQFLTH 751
Cdd:cd04375  178 RMQRkkslgkpdqkELSENKAAHQCLAYMIEE 209
RhoGAP_Bcr cd04387
RhoGAP_Bcr: RhoGAP (GTPase-activator protein [GAP] for Rho-like small GTPases) domain of Bcr ...
597-733 2.22e-05

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: 46.07  E-value: 2.22e-05
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 741922299 597 VDYLYRNAIQQEDLFQQPGLRSEFDHIRDCLDTGMIDNLSASN----HSVAEALLLFLESLPEPVIC---YSAYRNCLEC 669
Cdd:cd04387   24 VEEVERRGMEEVGIYRISGVATDIQALKAAFDTNNKDVSVMLSemdvNAIAGTLKLYFRELPEPLFTdelYPNFAEGIAL 103
                         90       100       110       120       130       140
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 741922299 670 SGNLAASK---QVITALPACHRNVFTYLMAFLQELLKNSAKNHLDDNILASIFGSLLLRNPAGHQKL 733
Cdd:cd04387  104 SDPVAKEScmlNLLLSLPDPNLVTFLFLLHHLKRVAEREEVNKMSLHNLATVFGPTLLRPSEKESKI 170
RhoGAP_MgcRacGAP cd04382
RhoGAP_MgcRacGAP: RhoGAP (GTPase-activator protein [GAP] for Rho-like small GTPases) domain ...
606-720 5.31e-05

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: 44.98  E-value: 5.31e-05
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 741922299 606 QQEDLFQQPGLRSEFDHIRDCLDTG-MIDNLSASN-HSVAEALLLFLESLPEPVICYSAYRNCLECSGNL------AASK 677
Cdd:cd04382   34 TEEGLYRVSGSEREVKALKEKFLRGkTVPNLSKVDiHVICGCLKDFLRSLKEPLITFALWKEFMEAAEILdednsrAALY 113
                         90       100       110       120
                 ....*....|....*....|....*....|....*....|...
gi 741922299 678 QVITALPACHRNVFTYLMAFLQELLKNSAkNHLDDNILASIFG 720
Cdd:cd04382  114 QAISELPQPNRDTLAFLILHLQRVAQSPE-CKMDINNLARVFG 155
RhoGAP_ARAP cd04385
RhoGAP_ARAP: RhoGAP (GTPase-activator protein [GAP] for Rho-like small GTPases) domain present ...
570-724 1.45e-04

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


Pssm-ID: 239850  Cd Length: 184  Bit Score: 43.45  E-value: 1.45e-04
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 741922299 570 TLMQLQTEDNgsqlekpmDIPkelwILVD----YLYRNAIQQEDLFQQPGLRSEFDHI-----RDCLDTGMIDNlSASNH 640
Cdd:cd04385    4 ALEDQQLTDN--------DIP----VIVDkcidFITQHGLMSEGIYRKNGKNSSVKKLleafrKDARSVQLREG-EYTVH 70
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 741922299 641 SVAEALLLFLESLPEPVICYSAYRNCLECSG------NLAASKQVITALPACHRNVFTYLMAFLQELLKNSAKNHLDDNI 714
Cdd:cd04385   71 DVADVLKRFLRDLPDPLLTSELHAEWIEAAElenkdeRIARYKELIRRLPPINRATLKVLIGHLYRVQKHSDENQMSVHN 150
                        170
                 ....*....|
gi 741922299 715 LASIFGSLLL 724
Cdd:cd04385  151 LALVFGPTLF 160
RhoGAP_ARHGAP27_15_12_9 cd04403
RhoGAP_ARHGAP27_15_12_9: GTPase-activator protein (GAP) domain for Rho-like GTPases found in ...
597-726 1.51e-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: 43.53  E-value: 1.51e-04
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 741922299 597 VDYLYR-----NAIQQedlfqqpgLRSEFDHIRdcldtgMIDNLSASN---HSVAEALLLFLESLPEPVICYSAYRNCLE 668
Cdd:cd04403   34 VDGIYRvsgnlAVIQK--------LRFAVDHDE------KLDLDDSKWediHVITGALKLFFRELPEPLFPYSLFNDFVA 99
                         90       100       110       120       130       140
                 ....*....|....*....|....*....|....*....|....*....|....*....|....
gi 741922299 669 CSGN------LAASKQVITALPACHRNVFTYLMAFLQELLKNSAKNHLDDNILASIFGSLLLRN 726
Cdd:cd04403  100 AIKLsdyeqrVSAVKDLIKSLPKPNHDTLKMLFRHLCRVIEHGEKNRMTTQNLAIVFGPTLLRP 163
RhoGAP_fSAC7_BAG7 cd04396
RhoGAP_fSAC7_BAG7: RhoGAP (GTPase-activator protein [GAP] for Rho-like small GTPases) domain ...
599-749 2.09e-04

RhoGAP_fSAC7_BAG7: RhoGAP (GTPase-activator protein [GAP] for Rho-like small GTPases) domain of fungal SAC7 and BAG7-like proteins. Both proteins are GTPase activating proteins of Rho1, but differ functionally in vivo: SAC7, but not BAG7, is involved in the control of Rho1-mediated activation of the PKC-MPK1 pathway. 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: 239861  Cd Length: 225  Bit Score: 43.55  E-value: 2.09e-04
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 741922299 599 YLYRNAIQQEDLFQQPGLRSEFDHIRDCLDTG-----MIDNLSASNHSVAEALLLFLESLPEPVI---CYSAYRNCLECS 670
Cdd:cd04396   42 YLKENATEVEGIFRVAGSSKRIRELQLIFSTPpdygkSFDWDGYTVHDAASVLRRYLNNLPEPLVpldLYEEFRNPLRKR 121
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 741922299 671 GNLAAS--------------------KQVITALPACHRNVFTYLMAFLQELLKNSAKNHLDDNILASIFGSLLLrnpaGH 730
Cdd:cd04396  122 PRILQYmkgrineplntdidqaikeyRDLITRLPNLNRQLLLYLLDLLAVFARNSDKNLMTASNLAAIFQPGIL----SH 197
                        170       180
                 ....*....|....*....|
gi 741922299 731 QKLEMAEKK-KAQEFVHQFL 749
Cdd:cd04396  198 PDHEMDPKEyKLSRLVVEFL 217
RhoGAP_ARHGAP18 cd04391
RhoGAP_ARHGAP18: RhoGAP (GTPase-activator protein [GAP] for Rho-like small GTPases) domain of ...
578-708 2.71e-04

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


Pssm-ID: 239856  Cd Length: 216  Bit Score: 43.10  E-value: 2.71e-04
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 741922299 578 DNGSQLEKPMDIPKELWILVDYLYRNAIQQEDLFQQPGLRSEFDHIRDCLDT----GMIDNLSASNHSVAEALLLFLESL 653
Cdd:cd04391   11 ERDQKKVPGSKVPLIFQKLINKLEERGLETEGILRIPGSAQRVKFLCQELEAkfyeGTFLWDQVKQHDAASLLKLFIREL 90
                         90       100       110       120       130       140
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 741922299 654 PEPVIC---YSAYRNCLecsgNLAASKQVITAL-------PACHRNVFTYLMAFLQELLKNSAKN 708
Cdd:cd04391   91 PQPLLTveyLPAFYSVQ----GLPSKKDQLQALnllvlllPEANRDTLKALLEFLQKVVDHEEKN 151
INPP5A cd09092
Type I inositol polyphosphate 5-phosphatase I; Type I inositol polyphosphate 5-phosphatase I ...
333-398 1.44e-03

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: 41.69  E-value: 1.44e-03
                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 741922299 333 EGELTFQPTYKYdtgSDDWDTSE---KCRAPAWCDRVLWKgKNITQLSYQSH----------MALKTSDHKPVSSVFDI 398
Cdd:cd09092  309 ELDISFPPSYPY---SEDPEQGTqymNTRCPAWCDRILMS-HSARELKSENEeksvtydmigPNVCMGDHKPVFLTFRI 383
RhoGAP_SYD1 cd04379
RhoGAP_SYD1: RhoGAP (GTPase-activator protein [GAP] for Rho-like small GTPases) domain present ...
649-724 9.14e-03

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


Pssm-ID: 239844  Cd Length: 207  Bit Score: 38.22  E-value: 9.14e-03
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 741922299 649 FLESLPEPVICYSAYRNCLE-----------CSGNLAASkqVITALPACHRNVFTYLMAFLQELLKNSAKNHLDDNILAS 717
Cdd:cd04379   83 YLRELPEPLITPQLYEMVLEalavalpndvqTNTHLTLS--IIDCLPLSAKATLLLLLDHLSLVLSNSERNKMTPQNLAV 160

                 ....*..
gi 741922299 718 IFGSLLL 724
Cdd:cd04379  161 CFGPVLM 167
 
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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