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Conserved domains on  [gi|1375859431|ref|XP_024456703|]
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type I inositol polyphosphate 5-phosphatase 4 isoform X1 [Populus trichocarpa]

Protein Classification

exonuclease/endonuclease/phosphatase family protein( domain architecture ID 662)

exonuclease/endonuclease/phosphatase (EEP) family protein may cleave phosphodiester bonds

Graphical summary

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List of domain hits

 Name Accession Description Interval E-value
EEP super family cl00490
Exonuclease-Endonuclease-Phosphatase (EEP) domain superfamily; This large superfamily includes ...
 50-546 9.12e-145

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.


The actual alignment was detected with superfamily member PLN03191:

Pssm-ID: 469791 [Multi-domain]  Cd Length: 621  Bit Score: 431.25  E-value: 9.12e-145
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1375859431  50 EKHAPSRKAKQVQYQT-----PPSIETSY-RRHsggvQRGKIDLDAAQVTDVNNYRIFVATWNVAGKSPPSHLNLEDWLH 123
Cdd:PLN03191   58 EDHANRRQGNQSVFGNqisdgGVSVSKGYsSKH----RRGKSETLRAQYINTKDIRVTIGTWNVAGRLPSEDLEIEDWLS 133

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1375859431 124 TSPPADIYVLGFQEIVPLNAGNVLGTEDNGPGKKWLALIRKTLN--SLPGTSWGYHT--PSPV------SDPIVE----- 188
Cdd:PLN03191  134 TEEPADIYIIGFQEVVPLNAGNVLGAEDSRPIPKWEAIIRRTLNksNKPESKHKSYSapPSPVlrtsivADELAEevdsl 213

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1375859431 189 ----LDADFEGSTRQKASSFFHR-RSFQSLSRSMRMDGDMVIPQPKLDRRFSVCDRVIFG--NRPSDYDP---------- 251
Cdd:PLN03191  214 plemMNNEFIDAATGCPSLEPERnKNIGWPEHSLDATPQVVSSNSKLRRVFSSSARLGFKwpENPSLFSPqrfalnargl 293

                         250       260       270       280       290       300       310       320
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1375859431 252 ----------NYQWGSSDDENGPGDSPlATQHSPIDYSGSLSMEDRD---------------RQTGQSR--YCLVACKQM 304
Cdd:PLN03191  294 krshrsfgnlGLSWNEIKQRSEVPEVP-EVIDSLSDVSDRSSEAEDDtfkevpsyqlpedliKDCRKVKqkYVRIVSKQM 372

                         330       340       350       360       370       380       390       400
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1375859431 305 VGVFLTVWVKSDLRDDVRNLKVSCVGRGLMGYLGNKGSISISMALHQTSFCFICSHLTSGQKEGDELRRNSDVMEILRKT 384
Cdd:PLN03191  373 VGIYVSVWVRKRLRRHINNLKVSPVGVGLMGYMGNKGSVSISMSLFQSRLCFVCSHLTSGHKDGAEQRRNADVYEIIRRT 452

                         410       420       430       440       450       460       470       480
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1375859431 385 RFPRVHsrgDKNSPQTILEHDRIIWLGDLNYRIALSYRAVKTLVEMQNWRALLENDQLRIEQGRGRVFDGWNEGKIYFPP 464
Cdd:PLN03191  453 RFSSVL---DTDQPQTIPSHDQIFWFGDLNYRLNMLDTEVRKLVAQKRWDELINSDQLIKELRSGHVFDGWKEGPIKFPP 529

                         490       500       510       520       530       540       550       560
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1375859431 465 TYKYSNNSDRYAGDDRHPKEKRRTPAWCDRILWYGRGLTQLSYVRGESRFSDHRPVCGVFLAEVESINRSRIKKSMSCSN 544
Cdd:PLN03191  530 TYKYEINSDRYVGENPKEGEKKRSPAWCDRILWLGKGIKQLCYKRSEIRLSDHRPVSSMFLVEVEVFDHRKLQRALNVNS 609


                  ..
gi 1375859431 545 SR 546
Cdd:PLN03191  610 AA 611
 
Name Accession Description Interval E-value
PLN03191 PLN03191
Type I inositol-1,4,5-trisphosphate 5-phosphatase 2; Provisional
 50-546 9.12e-145

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


Pssm-ID: 215624 [Multi-domain]  Cd Length: 621  Bit Score: 431.25  E-value: 9.12e-145
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1375859431  50 EKHAPSRKAKQVQYQT-----PPSIETSY-RRHsggvQRGKIDLDAAQVTDVNNYRIFVATWNVAGKSPPSHLNLEDWLH 123
Cdd:PLN03191   58 EDHANRRQGNQSVFGNqisdgGVSVSKGYsSKH----RRGKSETLRAQYINTKDIRVTIGTWNVAGRLPSEDLEIEDWLS 133

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1375859431 124 TSPPADIYVLGFQEIVPLNAGNVLGTEDNGPGKKWLALIRKTLN--SLPGTSWGYHT--PSPV------SDPIVE----- 188
Cdd:PLN03191  134 TEEPADIYIIGFQEVVPLNAGNVLGAEDSRPIPKWEAIIRRTLNksNKPESKHKSYSapPSPVlrtsivADELAEevdsl 213

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1375859431 189 ----LDADFEGSTRQKASSFFHR-RSFQSLSRSMRMDGDMVIPQPKLDRRFSVCDRVIFG--NRPSDYDP---------- 251
Cdd:PLN03191  214 plemMNNEFIDAATGCPSLEPERnKNIGWPEHSLDATPQVVSSNSKLRRVFSSSARLGFKwpENPSLFSPqrfalnargl 293

                         250       260       270       280       290       300       310       320
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1375859431 252 ----------NYQWGSSDDENGPGDSPlATQHSPIDYSGSLSMEDRD---------------RQTGQSR--YCLVACKQM 304
Cdd:PLN03191  294 krshrsfgnlGLSWNEIKQRSEVPEVP-EVIDSLSDVSDRSSEAEDDtfkevpsyqlpedliKDCRKVKqkYVRIVSKQM 372

                         330       340       350       360       370       380       390       400
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1375859431 305 VGVFLTVWVKSDLRDDVRNLKVSCVGRGLMGYLGNKGSISISMALHQTSFCFICSHLTSGQKEGDELRRNSDVMEILRKT 384
Cdd:PLN03191  373 VGIYVSVWVRKRLRRHINNLKVSPVGVGLMGYMGNKGSVSISMSLFQSRLCFVCSHLTSGHKDGAEQRRNADVYEIIRRT 452

                         410       420       430       440       450       460       470       480
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1375859431 385 RFPRVHsrgDKNSPQTILEHDRIIWLGDLNYRIALSYRAVKTLVEMQNWRALLENDQLRIEQGRGRVFDGWNEGKIYFPP 464
Cdd:PLN03191  453 RFSSVL---DTDQPQTIPSHDQIFWFGDLNYRLNMLDTEVRKLVAQKRWDELINSDQLIKELRSGHVFDGWKEGPIKFPP 529

                         490       500       510       520       530       540       550       560
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1375859431 465 TYKYSNNSDRYAGDDRHPKEKRRTPAWCDRILWYGRGLTQLSYVRGESRFSDHRPVCGVFLAEVESINRSRIKKSMSCSN 544
Cdd:PLN03191  530 TYKYEINSDRYVGENPKEGEKKRSPAWCDRILWLGKGIKQLCYKRSEIRLSDHRPVSSMFLVEVEVFDHRKLQRALNVNS 609


                  ..
gi 1375859431 545 SR 546
Cdd:PLN03191  610 AA 611
INPP5c_INPP5B cd09093
Catalytic inositol polyphosphate 5-phosphatase (INPP5c) domain of Type II inositol ...
 99-524 2.92e-79

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: 251.08  E-value: 2.92e-79
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1375859431  99 RIFVATWNVAGKSPPShlNLEDWLHTSP-PADIYVLGFQEIvPLNAGNVLgTEDNGPGKKWLALIRKTLNSlpgtswgyh 177
Cdd:cd09093     2 RIFVGTWNVNGQSPDE--SLRPWLSCDEePPDIYAIGFQEL-DLSAEAFL-FNDSSREQEWVKAVERGLHP--------- 68

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1375859431 178 tpspvsdpiveldadfegstrqkassffhrrsfqslsrsmrmdgdmvipqpkldrrfsvcdrvifgnrpsdydpnyqwgs 257
Cdd:cd09093       --------------------------------------------------------------------------------

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1375859431 258 sddengpgdsplatqhspidysgslsmedrdrqtgQSRYCLVACKQMVGVFLTVWVKSDLRDDVRNLKVSCVGRGLMGYL 337
Cdd:cd09093    69 -----------------------------------DAKYKKVKLIRLVGMMLLVFVKKEHRQHIKEVAAETVGTGIMGKM 113

                         250       260       270       280       290       300       310       320
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1375859431 338 GNKGSISISMALHQTSFCFICSHLTSGQkeGDELRRNSDVMEILRKTRFPRVHSrgdknSPQTILEHDRIIWLGDLNYRI 417
Cdd:cd09093   114 GNKGGVAVRFQFHNTTFCFVNSHLAAHM--EEVERRNQDYKDICARMKFEDPDG-----PPLSISDHDVVFWLGDLNYRI 186

                         330       340       350       360       370       380       390       400
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1375859431 418 A-LSYRAVKTLVEMQNWRALLENDQLRIEQGRGRVFDGWNEGKIYFPPTYKYSNNSDRYagDDRhpkEKRRTPAWCDRIL 496
Cdd:cd09093   187 QeLPTEEVKELIEKNDLEELLKYDQLNIQRRAGKVFEGFTEGEINFIPTYKYDPGTDNW--DSS---EKCRAPAWCDRIL 261

                         410       420
                  ....*....|....*....|....*....
gi 1375859431 497 WYGRGLTQLSYVRGES-RFSDHRPVCGVF 524
Cdd:cd09093   262 WRGTNIVQLSYRSHMElKTSDHKPVSALF 290
IPPc smart00128
Inositol polyphosphate phosphatase, catalytic domain homologues; Mg(2+)-dependent/Li(+) ...
 283-528 1.83e-60

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


Pssm-ID: 214525 [Multi-domain]  Cd Length: 306  Bit Score: 202.58  E-value: 1.83e-60
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1375859431  283 SMEDRDRQTGQSRYCLVACKQMVGVFLTVWVKSDLRDDVRNLKVSCVGRGLMGYLGNKGSISISMALHQTSFCFICSHLT 362
Cdd:smart00128  68 SDLLESSLNGDGQYNVLAKVYLVGILVLVFVKANHLVYIKDVETFTVKTGMGGLWGNKGAVAVRFKLSDTSFCFVNSHLA 147

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1375859431  363 SGQKEGDelRRNSDVMEILRKTRFPrvhsRGDKNSpqtILEHDRIIWLGDLNYRIAL-SYRAVKTLVEMQNWRALLENDQ 441
Cdd:smart00128 148 AGASNVE--QRNQDYKTILRALSFP----ERALLS---QFDHDVVFWFGDLNFRLDSpSYEEVRRKISKKEFDDLLEKDQ 218

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1375859431  442 LRIEQGRGRVFDGWNEGKIYFPPTYKY-SNNSDRYagddrHPKEKRRTPAWCDRILW--YGRGLTQLS--YVRGESRFSD 516
Cdd:smart00128 219 LNRQREAGKVFKGFQEGPITFPPTYKYdSVGTETY-----DTSEKKRVPAWCDRILYrsNGPELIQLSeyHSGMEITTSD 293

                          250
                   ....*....|..
gi 1375859431  517 HRPVCGVFLAEV 528
Cdd:smart00128 294 HKPVFATFRLKV 305
COG5411 COG5411
Phosphatidylinositol 5-phosphate phosphatase [Signal transduction mechanisms];
282-534 1.78e-41

Phosphatidylinositol 5-phosphate phosphatase [Signal transduction mechanisms];


Pssm-ID: 227698 [Multi-domain]  Cd Length: 460  Bit Score: 155.71  E-value: 1.78e-41
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1375859431 282 LSMEDRDRQtgqsrYCLVACKQMVGVFLTVWVKSDLRDDVRNLKVSCVGRGLMGYLGNKGSISISMALHQTSFCFICSHL 361
Cdd:COG5411   100 LNGAQSDEK-----YSLLRSPQLGGILLRVFSLATNLPVVKPVSGTVKKTGFGGSSSNKGAVAIRFNYERTSFCFVNSHL 174

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1375859431 362 TSGQKEGDElrRNSDVMEILRKTRFPRvhsrgdknsPQTILEHDRIIWLGDLNYRIALSYRAVKTLVEMQNWRA--LLEN 439
Cdd:COG5411   175 AAGVNNIEE--RIFDYRSIASNICFSR---------GLRIYDHDTIFWLGDLNYRVTSTNEEVRPEIASDDGRLdkLFEY 243

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1375859431 440 DQLRIEQGRGRVFDGWNEGKIYFPPTYKYSNNSDRYagdDRhpKEKRRTPAWCDRILWYGRGLTQLSYVRGES-RFSDHR 518
Cdd:COG5411   244 DQLLWEMEVGNVFPGFKEPVITFPPTYKFDYGTDEY---DT--SDKGRIPSWTDRILYKSEQLTPHSYSSIPHlMISDHR 318

                         250
                  ....*....|....*.
gi 1375859431 519 PVCGVFLAEVESINRS 534
Cdd:COG5411   319 PVYATFRAKIKVVDPS 334
 
Name Accession Description Interval E-value
PLN03191 PLN03191
Type I inositol-1,4,5-trisphosphate 5-phosphatase 2; Provisional
 50-546 9.12e-145

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


Pssm-ID: 215624 [Multi-domain]  Cd Length: 621  Bit Score: 431.25  E-value: 9.12e-145
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1375859431  50 EKHAPSRKAKQVQYQT-----PPSIETSY-RRHsggvQRGKIDLDAAQVTDVNNYRIFVATWNVAGKSPPSHLNLEDWLH 123
Cdd:PLN03191   58 EDHANRRQGNQSVFGNqisdgGVSVSKGYsSKH----RRGKSETLRAQYINTKDIRVTIGTWNVAGRLPSEDLEIEDWLS 133

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1375859431 124 TSPPADIYVLGFQEIVPLNAGNVLGTEDNGPGKKWLALIRKTLN--SLPGTSWGYHT--PSPV------SDPIVE----- 188
Cdd:PLN03191  134 TEEPADIYIIGFQEVVPLNAGNVLGAEDSRPIPKWEAIIRRTLNksNKPESKHKSYSapPSPVlrtsivADELAEevdsl 213

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1375859431 189 ----LDADFEGSTRQKASSFFHR-RSFQSLSRSMRMDGDMVIPQPKLDRRFSVCDRVIFG--NRPSDYDP---------- 251
Cdd:PLN03191  214 plemMNNEFIDAATGCPSLEPERnKNIGWPEHSLDATPQVVSSNSKLRRVFSSSARLGFKwpENPSLFSPqrfalnargl 293

                         250       260       270       280       290       300       310       320
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1375859431 252 ----------NYQWGSSDDENGPGDSPlATQHSPIDYSGSLSMEDRD---------------RQTGQSR--YCLVACKQM 304
Cdd:PLN03191  294 krshrsfgnlGLSWNEIKQRSEVPEVP-EVIDSLSDVSDRSSEAEDDtfkevpsyqlpedliKDCRKVKqkYVRIVSKQM 372

                         330       340       350       360       370       380       390       400
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1375859431 305 VGVFLTVWVKSDLRDDVRNLKVSCVGRGLMGYLGNKGSISISMALHQTSFCFICSHLTSGQKEGDELRRNSDVMEILRKT 384
Cdd:PLN03191  373 VGIYVSVWVRKRLRRHINNLKVSPVGVGLMGYMGNKGSVSISMSLFQSRLCFVCSHLTSGHKDGAEQRRNADVYEIIRRT 452

                         410       420       430       440       450       460       470       480
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1375859431 385 RFPRVHsrgDKNSPQTILEHDRIIWLGDLNYRIALSYRAVKTLVEMQNWRALLENDQLRIEQGRGRVFDGWNEGKIYFPP 464
Cdd:PLN03191  453 RFSSVL---DTDQPQTIPSHDQIFWFGDLNYRLNMLDTEVRKLVAQKRWDELINSDQLIKELRSGHVFDGWKEGPIKFPP 529

                         490       500       510       520       530       540       550       560
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1375859431 465 TYKYSNNSDRYAGDDRHPKEKRRTPAWCDRILWYGRGLTQLSYVRGESRFSDHRPVCGVFLAEVESINRSRIKKSMSCSN 544
Cdd:PLN03191  530 TYKYEINSDRYVGENPKEGEKKRSPAWCDRILWLGKGIKQLCYKRSEIRLSDHRPVSSMFLVEVEVFDHRKLQRALNVNS 609


                  ..
gi 1375859431 545 SR 546
Cdd:PLN03191  610 AA 611
INPP5c_INPP5B cd09093
Catalytic inositol polyphosphate 5-phosphatase (INPP5c) domain of Type II inositol ...
 99-524 2.92e-79

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: 251.08  E-value: 2.92e-79
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1375859431  99 RIFVATWNVAGKSPPShlNLEDWLHTSP-PADIYVLGFQEIvPLNAGNVLgTEDNGPGKKWLALIRKTLNSlpgtswgyh 177
Cdd:cd09093     2 RIFVGTWNVNGQSPDE--SLRPWLSCDEePPDIYAIGFQEL-DLSAEAFL-FNDSSREQEWVKAVERGLHP--------- 68

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1375859431 178 tpspvsdpiveldadfegstrqkassffhrrsfqslsrsmrmdgdmvipqpkldrrfsvcdrvifgnrpsdydpnyqwgs 257
Cdd:cd09093       --------------------------------------------------------------------------------

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1375859431 258 sddengpgdsplatqhspidysgslsmedrdrqtgQSRYCLVACKQMVGVFLTVWVKSDLRDDVRNLKVSCVGRGLMGYL 337
Cdd:cd09093    69 -----------------------------------DAKYKKVKLIRLVGMMLLVFVKKEHRQHIKEVAAETVGTGIMGKM 113

                         250       260       270       280       290       300       310       320
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1375859431 338 GNKGSISISMALHQTSFCFICSHLTSGQkeGDELRRNSDVMEILRKTRFPRVHSrgdknSPQTILEHDRIIWLGDLNYRI 417
Cdd:cd09093   114 GNKGGVAVRFQFHNTTFCFVNSHLAAHM--EEVERRNQDYKDICARMKFEDPDG-----PPLSISDHDVVFWLGDLNYRI 186

                         330       340       350       360       370       380       390       400
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1375859431 418 A-LSYRAVKTLVEMQNWRALLENDQLRIEQGRGRVFDGWNEGKIYFPPTYKYSNNSDRYagDDRhpkEKRRTPAWCDRIL 496
Cdd:cd09093   187 QeLPTEEVKELIEKNDLEELLKYDQLNIQRRAGKVFEGFTEGEINFIPTYKYDPGTDNW--DSS---EKCRAPAWCDRIL 261

                         410       420
                  ....*....|....*....|....*....
gi 1375859431 497 WYGRGLTQLSYVRGES-RFSDHRPVCGVF 524
Cdd:cd09093   262 WRGTNIVQLSYRSHMElKTSDHKPVSALF 290
INPP5c cd09074
Catalytic domain of inositol polyphosphate 5-phosphatases; Inositol polyphosphate ...
 99-524 7.71e-75

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: 239.93  E-value: 7.71e-75
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1375859431  99 RIFVATWNVAGKSPPsHLNLEDWLH--TSPPADIYVLGFQEIVPLNAGNVlGTEDNGPGKKWLALIRKTLNSLPGtswgy 176
Cdd:cd09074     2 KIFVVTWNVGGGISP-PENLENWLSpkGTEAPDIYAVGVQEVDMSVQGFV-GNDDSAKAREWVDNIQEALNEKEN----- 74

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1375859431 177 htpspvsdpiveldadfegstrqkassffhrrsfqslsrsmrmdgdmvipqpkldrrfsvcdrvifgnrpsdydpnyqwg 256
Cdd:cd09074       --------------------------------------------------------------------------------

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1375859431 257 ssddengpgdsplatqhspidysgslsmedrdrqtgqsrYCLVACKQMVGVFLTVWVKSDLRDDVRNLKVSC--VGRGLM 334
Cdd:cd09074    75 ---------------------------------------YVLLGSAQLVGIFLFVFVKKEHLPQIKDLEVEGvtVGTGGG 115

                         250       260       270       280       290       300       310       320
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1375859431 335 GYLGNKGSISISMALHQTSFCFICSHLTSGQKEGDelRRNSDVMEILRKTRFPRVHSRGDKnspqtILEHDRIIWLGDLN 414
Cdd:cd09074   116 GKLGNKGGVAIRFQINDTSFCFVNSHLAAGQEEVE--RRNQDYRDILSKLKFYRGDPAIDS-----IFDHDVVFWFGDLN 188

                         330       340       350       360       370       380       390       400
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1375859431 415 YRIALSYRAVKTLVEMQNWRALLENDQLRIEQGRGRVFDGWNEGKIYFPPTYKYSNNSDRYagDDrhpKEKRRTPAWCDR 494
Cdd:cd09074   189 YRIDSTDDEVRKLISQGDLDDLLEKDQLKKQKEKGKVFDGFQELPITFPPTYKFDPGTDEY--DT---SDKKRIPAWCDR 263

                         410       420       430
                  ....*....|....*....|....*....|....
gi 1375859431 495 ILW---YGRGLTQLSYVR-GESRFSDHRPVCGVF 524
Cdd:cd09074   264 ILYkskAGSEIQPLSYTSvPLYKTSDHKPVRATF 297
INPP5c_Synj cd09089
Catalytic inositol polyphosphate 5-phosphatase (INPP5c) domain of synaptojanins; This ...
 99-524 1.04e-72

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: 235.36  E-value: 1.04e-72
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1375859431  99 RIFVATWNV-AGKSPPS----HLNLEDWLHTSP---------------PADIYVLGFQEIVPLNAGNVLGT-EDNGpgKK 157
Cdd:cd09089     2 RVFVGTWNVnGGKHFRSiafkHQSMTDWLLDNPklagqcsndseedekPVDIFAIGFEEMVDLNASNIVSAsTTNQ--KE 79

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1375859431 158 WLALIRKTLNslpgtswgyhtpspvsdpiveldadfegstrqkassffhrrsfqslsrsmrmdgdmvipqpkldrrfsvc 237
Cdd:cd09089    80 WGEELQKTIS---------------------------------------------------------------------- 89

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1375859431 238 drvifgnrpsdydpnyqwgssddengpgdsplatqhspidysgslsmedRDrqtgqSRYCLVACKQMVGVFLTVWVKSDL 317
Cdd:cd09089    90 -------------------------------------------------RD-----HKYVLLTSEQLVGVCLFVFVRPQH 115

                         250       260       270       280       290       300       310       320
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1375859431 318 RDDVRNLKVSCVGRGLMGYLGNKGSISISMALHQTSFCFICSHLTSGQKEGDElrRNSDVMEILRKTRFPrvhsrgdknS 397
Cdd:cd09089   116 APFIRDVAVDTVKTGLGGAAGNKGAVAIRFLLHSTSLCFVCSHFAAGQSQVKE--RNEDFAEIARKLSFP---------M 184

                         330       340       350       360       370       380       390       400
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1375859431 398 PQTILEHDRIIWLGDLNYRIALSYRAVKTLVEMQNWRALLENDQLRIEQGRGRVFDGWNEGKIYFPPTYKYSNNSDRYag 477
Cdd:cd09089   185 GRTLDSHDYVFWCGDFNYRIDLPNDEVKELVRNGDWLKLLEFDQLTKQKAAGNVFKGFLEGEINFAPTYKYDLFSDDY-- 262

                         410       420       430       440       450       460
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 1375859431 478 ddrHPKEKRRTPAWCDRILWYGRGLTQ--------------------LSYVRGESRFSDHRPVCGVF 524
Cdd:cd09089   263 ---DTSEKCRTPAWTDRVLWRRRKWPSdkteeslvetndptwnpgtlLYYGRAELKTSDHRPVVAII 326
INPP5c_ScInp51p-like cd09090
Catalytic inositol polyphosphate 5-phosphatase (INPP5c) domain of Saccharomyces cerevisiae ...
 99-526 7.90e-69

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: 223.76  E-value: 7.90e-69
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1375859431  99 RIFVATWNVAGKSPpsHLNLEDWLHTS---PPADIYVLGFQEIVPLNAGNVLGTEdngPGKK--WLALIRKTLNslpgts 173
Cdd:cd09090     2 NIFVGTFNVNGKSY--KDDLSSWLFPEendELPDIVVIGLQEVVELTAGQILNSD---PSKSsfWEKKIKTTLN------ 70

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1375859431 174 wgyhtpspvsdpiveldadfegstrqkassffhrrsfqslsrsmrmdgdmvipqpkldrrfsvcdrvifgnrpsdydpny 253
Cdd:cd09090       --------------------------------------------------------------------------------

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1375859431 254 qwgssddengpgdsplatqhspidysgslsmedrdrQTGQSRYCLVACKQMVGVFLTVWVKSDLRDDVRNLKVSCVGRGL 333
Cdd:cd09090    71 ------------------------------------GRGGEKYVLLRSEQLVGTALLFFVKESQLPKVKNVEGSTKKTGL 114

                         250       260       270       280       290       300       310       320
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1375859431 334 MGYLGNKGSISISMALHQTSFCFICSHLTSGQKEGDElrRNSDVMEILRKTRFPRvhsrgdknsPQTILEHDRIIWLGDL 413
Cdd:cd09090   115 GGMSGNKGAVAIRFDYGDTSFCFVTSHLAAGLTNYEE--RNNDYKTIARGLRFSR---------GRTIKDHDHVIWLGDF 183

                         330       340       350       360       370       380       390       400
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1375859431 414 NYRIALSYRAVKTLVEMQNWRALLENDQLRIEQGRGRVFDGWNEGKIYFPPTYKYSNNSDRYagddrHPKEKRRTPAWCD 493
Cdd:cd09090   184 NYRISLTNEDVRRFILNGKLDKLLEYDQLNQQMNAGEVFPGFSEGPITFPPTYKYDKGTDNY-----DTSEKQRIPAWTD 258

                         410       420       430
                  ....*....|....*....|....*....|...
gi 1375859431 494 RILWYGRGLTQLSYVRGESRFSDHRPVCGVFLA 526
Cdd:cd09090   259 RILYRGENLRQLSYNSAPLRFSDHRPVYATFEA 291
IPPc smart00128
Inositol polyphosphate phosphatase, catalytic domain homologues; Mg(2+)-dependent/Li(+) ...
 283-528 1.83e-60

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


Pssm-ID: 214525 [Multi-domain]  Cd Length: 306  Bit Score: 202.58  E-value: 1.83e-60
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1375859431  283 SMEDRDRQTGQSRYCLVACKQMVGVFLTVWVKSDLRDDVRNLKVSCVGRGLMGYLGNKGSISISMALHQTSFCFICSHLT 362
Cdd:smart00128  68 SDLLESSLNGDGQYNVLAKVYLVGILVLVFVKANHLVYIKDVETFTVKTGMGGLWGNKGAVAVRFKLSDTSFCFVNSHLA 147

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1375859431  363 SGQKEGDelRRNSDVMEILRKTRFPrvhsRGDKNSpqtILEHDRIIWLGDLNYRIAL-SYRAVKTLVEMQNWRALLENDQ 441
Cdd:smart00128 148 AGASNVE--QRNQDYKTILRALSFP----ERALLS---QFDHDVVFWFGDLNFRLDSpSYEEVRRKISKKEFDDLLEKDQ 218

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1375859431  442 LRIEQGRGRVFDGWNEGKIYFPPTYKY-SNNSDRYagddrHPKEKRRTPAWCDRILW--YGRGLTQLS--YVRGESRFSD 516
Cdd:smart00128 219 LNRQREAGKVFKGFQEGPITFPPTYKYdSVGTETY-----DTSEKKRVPAWCDRILYrsNGPELIQLSeyHSGMEITTSD 293

                          250
                   ....*....|..
gi 1375859431  517 HRPVCGVFLAEV 528
Cdd:smart00128 294 HKPVFATFRLKV 305
INPP5c_Synj2 cd09099
Catalytic inositol polyphosphate 5-phosphatase (INPP5c) domain of synaptojanin 2; This ...
 257-529 9.24e-56

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: 191.00  E-value: 9.24e-56
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1375859431 257 SSDDENGPGDSPLATQHSPIDYSG----SLSMEDRDRQTGQ--------SRYCLVACKQMVGVFLTVWVKSDLRDDVRNL 324
Cdd:cd09099    42 FQDDESNPPDIFAVGFEEMVELSAgnivNASTTNRKMWGEQlqkaisrsHRYILLTSAQLVGVCLFIFVRPYHVPFIRDV 121

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1375859431 325 KVSCVGRGLMGYLGNKGSISISMALHQTSFCFICSHLTSGQKEGDElrRNSDVMEILRKTRFPrvhsrgdknSPQTILEH 404
Cdd:cd09099   122 AIDTVKTGMGGKAGNKGAVAIRFQFYSTSFCFICSHLTAGQNQVKE--RNEDYKEITQKLSFP---------MGRNVFSH 190

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1375859431 405 DRIIWLGDLNYRIALSYRAVKTLVEMQNWRALLENDQLRIEQGRGRVFDGWNEGKIYFPPTYKYSNNSDRYAGDDrhpke 484
Cdd:cd09099   191 DYVFWCGDFNYRIDLTYEEVFYFIKRQDWKKLLEFDQLQLQKSSGKIFKDFHEGTINFGPTYKYDVGSEAYDTSD----- 265

                         250       260       270       280       290       300       310
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 1375859431 485 KRRTPAWCDRILWYGRGL-----------------------------TQLSYVRGESRFSDHRPVcgvfLAEVE 529
Cdd:cd09099   266 KCRTPAWTDRVLWWRKKWpfektageinlldsdldfdtkirhtwtpgALMYYGRAELQASDHRPV----LAIVE 335
INPP5c_Synj1 cd09098
Catalytic inositol polyphosphate 5-phosphatase (INPP5c) domain of synaptojanin 1; This ...
 295-523 7.39e-55

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: 188.71  E-value: 7.39e-55
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1375859431 295 RYCLVACKQMVGVFLTVWVKSDLRDDVRNLKVSCVGRGLMGYLGNKGSISISMALHQTSFCFICSHLTSGQKEGDElrRN 374
Cdd:cd09098    92 KYVLLASEQLVGVCLFVFIRPQHAPFIRDVAVDTVKTGMGGATGNKGAVAIRMLFHTTSLCFVCSHFAAGQSQVKE--RN 169

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1375859431 375 SDVMEILRKTRFPRvhsrgdknsPQTILEHDRIIWLGDLNYRIALSYRAVKTLVEMQNWRALLENDQLRIEQGRGRVFDG 454
Cdd:cd09098   170 EDFIEIARKLSFPM---------GRMLFSHDYVFWCGDFNYRIDIPNEEVKELIRQQNWDSLIAGDQLINQKNAGQVFRG 240

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1375859431 455 WNEGKIYFPPTYKYSNNSDRYagddrHPKEKRRTPAWCDRILWYGRGL-----------------------------TQL 505
Cdd:cd09098   241 FLEGKLDFAPTYKYDLFSDDY-----DTSEKCRTPAWTDRVLWRRRKWpfdrsaedldllnasfpdnskeqytwspgTLL 315

                         250
                  ....*....|....*...
gi 1375859431 506 SYVRGESRFSDHRPVCGV 523
Cdd:cd09098   316 HYGRAELKTSDHRPVVAL 333
INPP5c_INPP5J-like cd09094
Catalytic inositol polyphosphate 5-phosphatase (INPP5c) domain of inositol polyphosphate ...
 296-526 3.02e-47

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: 167.16  E-value: 3.02e-47
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1375859431 296 YCLVACKQMVGVFLTVWVKSDLRDDVRNLKVSCVGRGLMGYLGNKGSISISMALHQTSFCFICSHLTSGQKEGDElrRNS 375
Cdd:cd09094    72 YVKVSSIRLQGLLLLVFVKIQHLPFIRDVQTNYTRTGLGGYWGNKGAVTVRFSLYGHMICFLNCHLPAHMEKWEQ--RID 149

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1375859431 376 DVMEILRKTRFPrvhsrgDKNSPqTILEHDRIIWLGDLNYRIA-LSYRAVKTLVEMQNWRALLENDQLRIEQGRGRVFDG 454
Cdd:cd09094   150 DFETILSTQVFN------ECNTP-SILDHDYVFWFGDLNFRIEdVSIEFVRELVNSKKYHLLLEKDQLNMAKRKEEAFQG 222

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1375859431 455 WNEGKIYFPPTYKYSNNSDRYagddrHPKEKRRTPAWCDRILW----------YGRGLTQLSYVRGES-RFSDHRPVCGV 523
Cdd:cd09094   223 FQEGPLNFAPTYKFDLGTDEY-----DTSGKKRKPAWTDRILWkvnpdasteeKFLSITQTSYKSHMEyGISDHKPVTAQ 297


                  ...
gi 1375859431 524 FLA 526
Cdd:cd09094   298 FRL 300
COG5411 COG5411
Phosphatidylinositol 5-phosphate phosphatase [Signal transduction mechanisms];
282-534 1.78e-41

Phosphatidylinositol 5-phosphate phosphatase [Signal transduction mechanisms];


Pssm-ID: 227698 [Multi-domain]  Cd Length: 460  Bit Score: 155.71  E-value: 1.78e-41
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1375859431 282 LSMEDRDRQtgqsrYCLVACKQMVGVFLTVWVKSDLRDDVRNLKVSCVGRGLMGYLGNKGSISISMALHQTSFCFICSHL 361
Cdd:COG5411   100 LNGAQSDEK-----YSLLRSPQLGGILLRVFSLATNLPVVKPVSGTVKKTGFGGSSSNKGAVAIRFNYERTSFCFVNSHL 174

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1375859431 362 TSGQKEGDElrRNSDVMEILRKTRFPRvhsrgdknsPQTILEHDRIIWLGDLNYRIALSYRAVKTLVEMQNWRA--LLEN 439
Cdd:COG5411   175 AAGVNNIEE--RIFDYRSIASNICFSR---------GLRIYDHDTIFWLGDLNYRVTSTNEEVRPEIASDDGRLdkLFEY 243

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1375859431 440 DQLRIEQGRGRVFDGWNEGKIYFPPTYKYSNNSDRYagdDRhpKEKRRTPAWCDRILWYGRGLTQLSYVRGES-RFSDHR 518
Cdd:COG5411   244 DQLLWEMEVGNVFPGFKEPVITFPPTYKFDYGTDEY---DT--SDKGRIPSWTDRILYKSEQLTPHSYSSIPHlMISDHR 318

                         250
                  ....*....|....*.
gi 1375859431 519 PVCGVFLAEVESINRS 534
Cdd:COG5411   319 PVYATFRAKIKVVDPS 334
INPP5c_SHIP cd09091
Catalytic inositol polyphosphate 5-phosphatase (INPP5c) domain of SH2 domain containing ...
 296-524 4.05e-36

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: 137.00  E-value: 4.05e-36
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1375859431 296 YCLVACKQMVGVFLTVWVKSDLRDDVRNLKVSCVGRGLMGYLGNKGSISISMALHQTSFCFICSHLTSGQKEgdELRRNS 375
Cdd:cd09091    74 YKPIAMQTLWNIRIVVLAKPEHENRISHVCTSSVKTGIANTLGNKGAVGVSFMFNGTSFGFVNSHLTSGSEK--KLRRNQ 151

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1375859431 376 DVMEILrktrfpRVHSRGDK--NSPQTILEHDRIIWLGDLNYRIALSYRAVKTLV---EMQNWRALLENDQLRIEQGRGR 450
Cdd:cd09091   152 NYLNIL------RFLSLGDKklSAFNITHRFTHLFWLGDLNYRLDLPIQEAENIIqkiEQQQFEPLLRHDQLNLEREEHK 225

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1375859431 451 VFDGWNEGKIYFPPTYKYSNNS-DRYAGDDRHPKE-KRRTPAWCDRILWYGRGLTQL---SY-VRGESRFSDHRPVCGVF 524
Cdd:cd09091   226 VFLRFSEEEITFPPTYRYERGSrDTYAYTKQKATGvKYNLPSWCDRILWKSYPETHIicqSYgCTDDIVTSDHSPVFGTF 305
INPP5c_INPP5E-like cd09095
Catalytic inositol polyphosphate 5-phosphatase (INPP5c) domain of Inositol ...
 340-524 1.83e-35

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: 134.86  E-value: 1.83e-35
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1375859431 340 KGSISISMALHQTSFCFICSHLTSGQKEGDElrRNSDVMEILRKTRFPR-VHSRGDK-NSPQTILEHDRIIWLGDLNYRI 417
Cdd:cd09095   110 KGALAISFTFFGTSFLFITSHFTSGDGKVKE--RVLDYNKIIQALNLPRnVPTNPYKsESGDVTTRFDEVFWFGDFNFRL 187

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1375859431 418 ALSYRAVKTLVEM---QNWRALLENDQLRIEQGRGRVFDGWNEGKIYFPPTYKYSNNSDRYagddrHPKEKRRTPAWCDR 494
Cdd:cd09095   188 SGPRHLVDALINQgqeVDVSALLQHDQLTREMSKGSIFKGFQEAPIHFPPTYKFDIGSDVY-----DTSSKQRVPSYTDR 262

                         170       180       190
                  ....*....|....*....|....*....|....
gi 1375859431 495 ILWYGRGLTQLSYVRGES----RFSDHRPVCGVF 524
Cdd:cd09095   263 ILYRSRQKGDVCCLKYNScpsiKTSDHRPVFALF 296
INPP5c_SHIP2-INPPL1 cd09101
Catalytic inositol polyphosphate 5-phosphatase (INPP5c) domain of SH2 domain containing ...
 296-524 9.87e-35

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: 133.17  E-value: 9.87e-35
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1375859431 296 YCLVACKQMVGVFLTVWVKSDLRDDVRNLKVSCVGRGLMGYLGNKGSISISMALHQTSFCFICSHLTSGQKEGDelRRNS 375
Cdd:cd09101    74 YQPIALQCLWNIKMVVLVKPEHENRISHVHTSSVKTGIANTLGNKGAVGVSFMFNGTSFGFVNCHLTSGNEKTH--RRNQ 151

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1375859431 376 DVMEILRKTrfprvhSRGDK--NSPQTILEHDRIIWLGDLNYRIALSYRAVKTLVEMQNWRALLENDQLRIEQGRGRVFD 453
Cdd:cd09101   152 NYLDILRSL------SLGDKqlNAFDISLRFTHLFWFGDLNYRLDMDIQEILNYITRKEFDPLLAVDQLNLEREKNKVFL 225

                         170       180       190       200       210       220       230
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 1375859431 454 GWNEGKIYFPPTYKYSNNS-DRYAGDDRHPKEKR-RTPAWCDRILWYGRGLTQL---SY-VRGESRFSDHRPVCGVF 524
Cdd:cd09101   226 RFREEEISFPPTYRYERGSrDTYMWQKQKTTGMRtNVPSWCDRILWKSYPETHIvcnSYgCTDDIVTSDHSPVFGTF 302
INPP5c_SHIP1-INPP5D cd09100
Catalytic inositol polyphosphate 5-phosphatase (INPP5c) domain of SH2 domain containing ...
 289-524 8.85e-34

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: 130.49  E-value: 8.85e-34
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1375859431 289 RQTGQSRYCLVACKQMVGVFLTVWVKSDLRDDVRNLKVSCVGRGLMGYLGNKGSISISMALHQTSFCFICSHLTSGQKEg 368
Cdd:cd09100    67 REITSISFKVIAIQTLWNIRIVVLAKPEHENRISHICTDSVKTGIANTLGNKGAVGVSFMFNGTSFGFVNSHLTSGSEK- 145

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1375859431 369 dELRRNSDVMEILRKTRFprvhsrGDKN-SPQTILEH-DRIIWLGDLNYRIALSYRAVKTLVE---MQNWRALLENDQLR 443
Cdd:cd09100   146 -KLRRNQNYFNILRFLVL------GDKKlSPFNITHRfTHLFWLGDLNYRVELPNTEAENIIQkikQQQYQELLPHDQLL 218

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1375859431 444 IEQGRGRVFDGWNEGKIYFPPTYKYSNNS-DRYA-GDDRHPKEKRRTPAWCDRILWYGRGLTQL---SY-VRGESRFSDH 517
Cdd:cd09100   219 IERKESKVFLQFEEEEITFAPTYRFERGTrERYAyTKQKATGMKYNLPSWCDRVLWKSYPLVHVvcqSYgCTDDITTSDH 298


                  ....*..
gi 1375859431 518 RPVCGVF 524
Cdd:cd09100   299 SPVFATF 305
INPP5A cd09092
Type I inositol polyphosphate 5-phosphatase I; Type I inositol polyphosphate 5-phosphatase I ...
 428-496 2.66e-04

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


Pssm-ID: 197326  Cd Length: 383  Bit Score: 43.61  E-value: 2.66e-04
                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|.
gi 1375859431 428 VEMQNWRALLENDQLRIEQGRGRVFdgwnEGKIYFPPTYKYSNnsdryagDDRHPKE--KRRTPAWCDRIL 496
Cdd:cd09092   284 VFRDNNGKALLKFDKELEVFKDVLY----ELDISFPPSYPYSE-------DPEQGTQymNTRCPAWCDRIL 343
 
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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