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Conserved domains on  [gi|1063699537|ref|NP_001323556|]
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DNAse I-like superfamily protein [Arabidopsis thaliana]

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 ...
2-375 5.58e-91

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: 286.80  E-value: 5.58e-91
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1063699537   2 WPRLVANKILRKSLGSNNFVADFPPNTDQKLIEASGLADER-------------SKSILHNQ---------------HK- 52
Cdd:PLN03191   13 WPSIVMKKWLNIKPKVYDFSEDEYDTETESEDDACSVKDVRvnvdedhanrrqgNQSVFGNQisdggvsvskgysskHRr 92
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1063699537  53 ----TTLLNY------KVFVSTWNVGGIVPDDGLDMEDLLETHKtPCDIYVLGFQEVVPLRASNVLGSDNNKVSTKWNSL 122
Cdd:PLN03191   93 gkseTLRAQYintkdiRVTIGTWNVAGRLPSEDLEIEDWLSTEE-PADIYIIGFQEVVPLNAGNVLGAEDSRPIPKWEAI 171
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1063699537 123 IRDALNKRARPHR-----------------------------------------------DED----------------- 138
Cdd:PLN03191  172 IRRTLNKSNKPESkhksysappspvlrtsivadelaeevdslplemmnnefidaatgcpsLEPernknigwpehsldatp 251
                         250       260       270       280       290       300       310       320
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1063699537 139 ---LSESK-----------GIN------------------GISQDFRC-------------------------------- 154
Cdd:PLN03191  252 qvvSSNSKlrrvfsssarlGFKwpenpslfspqrfalnarGLKRSHRSfgnlglswneikqrsevpevpevidslsdvsd 331
                         330       340       350       360       370       380       390       400
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1063699537 155 -----------------------------------IISKQMVGILITVWVRGDLWPYIRYPSVSCVGCGIMGCLGNKGSV 199
Cdd:PLN03191  332 rsseaeddtfkevpsyqlpedlikdcrkvkqkyvrIVSKQMVGIYVSVWVRKRLRRHINNLKVSPVGVGLMGYMGNKGSV 411
                         410       420       430       440       450       460       470       480
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1063699537 200 SVRFQLHETTFCFVCSHLASGGRDRDERQRNSDVNEILARSSFPRGSSLDLPKKILDHDRVIFLGDLNYRISLPEEKTRL 279
Cdd:PLN03191  412 SISMSLFQSRLCFVCSHLTSGHKDGAEQRRNADVYEIIRRTRFSSVLDTDQPQTIPSHDQIFWFGDLNYRLNMLDTEVRK 491
                         490       500       510       520       530       540       550       560
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1063699537 280 LVESKKWNILLENDQ---------IFRGWQEGIVKFAPTYKYVPNSDLYYGcITYKKDEKKRAPAWCDRIIWYGNGLKQH 350
Cdd:PLN03191  492 LVAQKRWDELINSDQlikelrsghVFDGWKEGPIKFPPTYKYEINSDRYVG-ENPKEGEKKRSPAWCDRILWLGKGIKQL 570
                         570       580
                  ....*....|....*....|....*
gi 1063699537 351 EYTRGETKISDHRPVKAIFTTEITV 375
Cdd:PLN03191  571 CYKRSEIRLSDHRPVSSMFLVEVEV 595
 
Name Accession Description Interval E-value
PLN03191 PLN03191
Type I inositol-1,4,5-trisphosphate 5-phosphatase 2; Provisional
2-375 5.58e-91

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


Pssm-ID: 215624 [Multi-domain]  Cd Length: 621  Bit Score: 286.80  E-value: 5.58e-91
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1063699537   2 WPRLVANKILRKSLGSNNFVADFPPNTDQKLIEASGLADER-------------SKSILHNQ---------------HK- 52
Cdd:PLN03191   13 WPSIVMKKWLNIKPKVYDFSEDEYDTETESEDDACSVKDVRvnvdedhanrrqgNQSVFGNQisdggvsvskgysskHRr 92
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1063699537  53 ----TTLLNY------KVFVSTWNVGGIVPDDGLDMEDLLETHKtPCDIYVLGFQEVVPLRASNVLGSDNNKVSTKWNSL 122
Cdd:PLN03191   93 gkseTLRAQYintkdiRVTIGTWNVAGRLPSEDLEIEDWLSTEE-PADIYIIGFQEVVPLNAGNVLGAEDSRPIPKWEAI 171
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1063699537 123 IRDALNKRARPHR-----------------------------------------------DED----------------- 138
Cdd:PLN03191  172 IRRTLNKSNKPESkhksysappspvlrtsivadelaeevdslplemmnnefidaatgcpsLEPernknigwpehsldatp 251
                         250       260       270       280       290       300       310       320
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1063699537 139 ---LSESK-----------GIN------------------GISQDFRC-------------------------------- 154
Cdd:PLN03191  252 qvvSSNSKlrrvfsssarlGFKwpenpslfspqrfalnarGLKRSHRSfgnlglswneikqrsevpevpevidslsdvsd 331
                         330       340       350       360       370       380       390       400
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1063699537 155 -----------------------------------IISKQMVGILITVWVRGDLWPYIRYPSVSCVGCGIMGCLGNKGSV 199
Cdd:PLN03191  332 rsseaeddtfkevpsyqlpedlikdcrkvkqkyvrIVSKQMVGIYVSVWVRKRLRRHINNLKVSPVGVGLMGYMGNKGSV 411
                         410       420       430       440       450       460       470       480
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1063699537 200 SVRFQLHETTFCFVCSHLASGGRDRDERQRNSDVNEILARSSFPRGSSLDLPKKILDHDRVIFLGDLNYRISLPEEKTRL 279
Cdd:PLN03191  412 SISMSLFQSRLCFVCSHLTSGHKDGAEQRRNADVYEIIRRTRFSSVLDTDQPQTIPSHDQIFWFGDLNYRLNMLDTEVRK 491
                         490       500       510       520       530       540       550       560
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1063699537 280 LVESKKWNILLENDQ---------IFRGWQEGIVKFAPTYKYVPNSDLYYGcITYKKDEKKRAPAWCDRIIWYGNGLKQH 350
Cdd:PLN03191  492 LVAQKRWDELINSDQlikelrsghVFDGWKEGPIKFPPTYKYEINSDRYVG-ENPKEGEKKRSPAWCDRILWLGKGIKQL 570
                         570       580
                  ....*....|....*....|....*
gi 1063699537 351 EYTRGETKISDHRPVKAIFTTEITV 375
Cdd:PLN03191  571 CYKRSEIRLSDHRPVSSMFLVEVEV 595
INPP5c_INPP5B cd09093
Catalytic inositol polyphosphate 5-phosphatase (INPP5c) domain of Type II inositol ...
59-369 1.28e-86

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: 264.95  E-value: 1.28e-86
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1063699537  59 KVFVSTWNVGGIVPDDGLDmeDLLETHKTPCDIYVLGFQEVvPLRASNVLGSDNNKvSTKWNSLIRDALNKRARphrded 138
Cdd:cd09093     2 RIFVGTWNVNGQSPDESLR--PWLSCDEEPPDIYAIGFQEL-DLSAEAFLFNDSSR-EQEWVKAVERGLHPDAK------ 71
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1063699537 139 lseskgingisqdFRCIISKQMVGILITVWVRGDLWPYIRYPSVSCVGCGIMGCLGNKGSVSVRFQLHETTFCFVCSHLA 218
Cdd:cd09093    72 -------------YKKVKLIRLVGMMLLVFVKKEHRQHIKEVAAETVGTGIMGKMGNKGGVAVRFQFHNTTFCFVNSHLA 138
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1063699537 219 SgGRDRDERqRNSDVNEILARSSFPRGSslDLPKKILDHDRVIFLGDLNYRIS-LPEEKTRLLVESKKWNILLENDQ--- 294
Cdd:cd09093   139 A-HMEEVER-RNQDYKDICARMKFEDPD--GPPLSISDHDVVFWLGDLNYRIQeLPTEEVKELIEKNDLEELLKYDQlni 214
                         250       260       270       280       290       300       310       320
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1063699537 295 ------IFRGWQEGIVKFAPTYKYVPNSDlyygciTYKKDEKKRAPAWCDRIIWYGNGLKQHEYTRG-ETKISDHRPVKA 367
Cdd:cd09093   215 qrragkVFEGFTEGEINFIPTYKYDPGTD------NWDSSEKCRAPAWCDRILWRGTNIVQLSYRSHmELKTSDHKPVSA 288

                  ..
gi 1063699537 368 IF 369
Cdd:cd09093   289 LF 290
IPPc smart00128
Inositol polyphosphate phosphatase, catalytic domain homologues; Mg(2+)-dependent/Li(+) ...
57-376 1.53e-74

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


Pssm-ID: 214525 [Multi-domain]  Cd Length: 306  Bit Score: 234.56  E-value: 1.53e-74
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1063699537   57 NYKVFVSTWNVGG------IVPDDGLDMEDLLETHKTpcDIYVLGFQEVVPLRASNVLGSDNNKVSTkWNSLIRDALNKR 130
Cdd:smart00128   2 DIKVLIGTWNVGGlespkvDVTSWLFQKIEVKQSEKP--DIYVIGLQEVVGLAPGVILETIAGKERL-WSDLLESSLNGD 78
                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1063699537  131 ArphrdedlseskgingisqDFRCIISKQMVGILITVWVRGDLWPYIRYPSVSCVGCGIMGCLGNKGSVSVRFQLHETTF 210
Cdd:smart00128  79 G-------------------QYNVLAKVYLVGILVLVFVKANHLVYIKDVETFTVKTGMGGLWGNKGAVAVRFKLSDTSF 139
                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1063699537  211 CFVCSHLASGGRDRDerQRNSDVNEILARSSFPRGSSLDlpkkILDHDRVIFLGDLNYRISLP-EEKTRLLVESKKWNIL 289
Cdd:smart00128 140 CFVNSHLAAGASNVE--QRNQDYKTILRALSFPERALLS----QFDHDVVFWFGDLNFRLDSPsYEEVRRKISKKEFDDL 213
                          250       260       270       280       290       300       310       320
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1063699537  290 LENDQ---------IFRGWQEGIVKFAPTYKYVP-NSDlyygciTYKKDEKKRAPAWCDRIIW----YGNGLKQHEYTRG 355
Cdd:smart00128 214 LEKDQlnrqreagkVFKGFQEGPITFPPTYKYDSvGTE------TYDTSEKKRVPAWCDRILYrsngPELIQLSEYHSGM 287
                          330       340
                   ....*....|....*....|.
gi 1063699537  356 ETKISDHRPVKAIFttEITVT 376
Cdd:smart00128 288 EITTSDHKPVFATF--RLKVT 306
COG5411 COG5411
Phosphatidylinositol 5-phosphate phosphatase [Signal transduction mechanisms];
38-381 1.95e-60

Phosphatidylinositol 5-phosphate phosphatase [Signal transduction mechanisms];


Pssm-ID: 227698 [Multi-domain]  Cd Length: 460  Bit Score: 202.71  E-value: 1.95e-60
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1063699537  38 LADERSKSILHNqhkttllNYKVFVSTWNVGGIVPDDglDMEDLL----ETHKTPcDIYVLGFQEVVPLRASNVLGSDNN 113
Cdd:COG5411    17 LRQRRSKYVIEK-------DVSIFVSTFNPPGKPPKA--STKRWLfpeiEATELA-DLYVVGLQEVVELTPGSILSADPY 86
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1063699537 114 KVSTKWNSLIRDALNKrarPHRDEDLSeskgingisqdfrCIISKQMVGILITVWVRGDLWPYIRYPSVSCVGCGIMGCL 193
Cdd:COG5411    87 DRLRIWESKVLDCLNG---AQSDEKYS-------------LLRSPQLGGILLRVFSLATNLPVVKPVSGTVKKTGFGGSS 150
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1063699537 194 GNKGSVSVRFQLHETTFCFVCSHLASGGRDRDERQrnSDVNEILARSSFPRGssldlpKKILDHDRVIFLGDLNYRISLP 273
Cdd:COG5411   151 SNKGAVAIRFNYERTSFCFVNSHLAAGVNNIEERI--FDYRSIASNICFSRG------LRIYDHDTIFWLGDLNYRVTST 222
                         250       260       270       280       290       300       310       320
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1063699537 274 EEKTRLLVESKKWNI--LLENDQI---------FRGWQEGIVKFAPTYKYVPNSDLYYgcitykKDEKKRAPAWCDRIIW 342
Cdd:COG5411   223 NEEVRPEIASDDGRLdkLFEYDQLlwemevgnvFPGFKEPVITFPPTYKFDYGTDEYD------TSDKGRIPSWTDRILY 296
                         330       340       350       360
                  ....*....|....*....|....*....|....*....|
gi 1063699537 343 YGNGLKQHEYTRGET-KISDHRPVKAIFTTEITVTRRGKK 381
Cdd:COG5411   297 KSEQLTPHSYSSIPHlMISDHRPVYATFRAKIKVVDPSKK 336
 
Name Accession Description Interval E-value
PLN03191 PLN03191
Type I inositol-1,4,5-trisphosphate 5-phosphatase 2; Provisional
2-375 5.58e-91

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


Pssm-ID: 215624 [Multi-domain]  Cd Length: 621  Bit Score: 286.80  E-value: 5.58e-91
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1063699537   2 WPRLVANKILRKSLGSNNFVADFPPNTDQKLIEASGLADER-------------SKSILHNQ---------------HK- 52
Cdd:PLN03191   13 WPSIVMKKWLNIKPKVYDFSEDEYDTETESEDDACSVKDVRvnvdedhanrrqgNQSVFGNQisdggvsvskgysskHRr 92
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1063699537  53 ----TTLLNY------KVFVSTWNVGGIVPDDGLDMEDLLETHKtPCDIYVLGFQEVVPLRASNVLGSDNNKVSTKWNSL 122
Cdd:PLN03191   93 gkseTLRAQYintkdiRVTIGTWNVAGRLPSEDLEIEDWLSTEE-PADIYIIGFQEVVPLNAGNVLGAEDSRPIPKWEAI 171
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1063699537 123 IRDALNKRARPHR-----------------------------------------------DED----------------- 138
Cdd:PLN03191  172 IRRTLNKSNKPESkhksysappspvlrtsivadelaeevdslplemmnnefidaatgcpsLEPernknigwpehsldatp 251
                         250       260       270       280       290       300       310       320
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1063699537 139 ---LSESK-----------GIN------------------GISQDFRC-------------------------------- 154
Cdd:PLN03191  252 qvvSSNSKlrrvfsssarlGFKwpenpslfspqrfalnarGLKRSHRSfgnlglswneikqrsevpevpevidslsdvsd 331
                         330       340       350       360       370       380       390       400
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1063699537 155 -----------------------------------IISKQMVGILITVWVRGDLWPYIRYPSVSCVGCGIMGCLGNKGSV 199
Cdd:PLN03191  332 rsseaeddtfkevpsyqlpedlikdcrkvkqkyvrIVSKQMVGIYVSVWVRKRLRRHINNLKVSPVGVGLMGYMGNKGSV 411
                         410       420       430       440       450       460       470       480
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1063699537 200 SVRFQLHETTFCFVCSHLASGGRDRDERQRNSDVNEILARSSFPRGSSLDLPKKILDHDRVIFLGDLNYRISLPEEKTRL 279
Cdd:PLN03191  412 SISMSLFQSRLCFVCSHLTSGHKDGAEQRRNADVYEIIRRTRFSSVLDTDQPQTIPSHDQIFWFGDLNYRLNMLDTEVRK 491
                         490       500       510       520       530       540       550       560
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1063699537 280 LVESKKWNILLENDQ---------IFRGWQEGIVKFAPTYKYVPNSDLYYGcITYKKDEKKRAPAWCDRIIWYGNGLKQH 350
Cdd:PLN03191  492 LVAQKRWDELINSDQlikelrsghVFDGWKEGPIKFPPTYKYEINSDRYVG-ENPKEGEKKRSPAWCDRILWLGKGIKQL 570
                         570       580
                  ....*....|....*....|....*
gi 1063699537 351 EYTRGETKISDHRPVKAIFTTEITV 375
Cdd:PLN03191  571 CYKRSEIRLSDHRPVSSMFLVEVEV 595
INPP5c_INPP5B cd09093
Catalytic inositol polyphosphate 5-phosphatase (INPP5c) domain of Type II inositol ...
59-369 1.28e-86

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: 264.95  E-value: 1.28e-86
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1063699537  59 KVFVSTWNVGGIVPDDGLDmeDLLETHKTPCDIYVLGFQEVvPLRASNVLGSDNNKvSTKWNSLIRDALNKRARphrded 138
Cdd:cd09093     2 RIFVGTWNVNGQSPDESLR--PWLSCDEEPPDIYAIGFQEL-DLSAEAFLFNDSSR-EQEWVKAVERGLHPDAK------ 71
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1063699537 139 lseskgingisqdFRCIISKQMVGILITVWVRGDLWPYIRYPSVSCVGCGIMGCLGNKGSVSVRFQLHETTFCFVCSHLA 218
Cdd:cd09093    72 -------------YKKVKLIRLVGMMLLVFVKKEHRQHIKEVAAETVGTGIMGKMGNKGGVAVRFQFHNTTFCFVNSHLA 138
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1063699537 219 SgGRDRDERqRNSDVNEILARSSFPRGSslDLPKKILDHDRVIFLGDLNYRIS-LPEEKTRLLVESKKWNILLENDQ--- 294
Cdd:cd09093   139 A-HMEEVER-RNQDYKDICARMKFEDPD--GPPLSISDHDVVFWLGDLNYRIQeLPTEEVKELIEKNDLEELLKYDQlni 214
                         250       260       270       280       290       300       310       320
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1063699537 295 ------IFRGWQEGIVKFAPTYKYVPNSDlyygciTYKKDEKKRAPAWCDRIIWYGNGLKQHEYTRG-ETKISDHRPVKA 367
Cdd:cd09093   215 qrragkVFEGFTEGEINFIPTYKYDPGTD------NWDSSEKCRAPAWCDRILWRGTNIVQLSYRSHmELKTSDHKPVSA 288

                  ..
gi 1063699537 368 IF 369
Cdd:cd09093   289 LF 290
INPP5c cd09074
Catalytic domain of inositol polyphosphate 5-phosphatases; Inositol polyphosphate ...
59-370 1.22e-78

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: 244.93  E-value: 1.22e-78
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1063699537  59 KVFVSTWNVGGIVPDDGLDMEDLLETHKTPCDIYVLGFQEVVPLRASNVlGSDNNKVSTKWNSLIRDALNKRArphrded 138
Cdd:cd09074     2 KIFVVTWNVGGGISPPENLENWLSPKGTEAPDIYAVGVQEVDMSVQGFV-GNDDSAKAREWVDNIQEALNEKE------- 73
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1063699537 139 lseskgingisqDFRCIISKQMVGILITVWVRGDLWPYIRYPSVSC--VGCGIMGCLGNKGSVSVRFQLHETTFCFVCSH 216
Cdd:cd09074    74 ------------NYVLLGSAQLVGIFLFVFVKKEHLPQIKDLEVEGvtVGTGGGGKLGNKGGVAIRFQINDTSFCFVNSH 141
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1063699537 217 LASGGRDRDerQRNSDVNEILARSSFPRGSSldLPKKILDHDRVIFLGDLNYRISLPEEKTRLLVESKKWNILLENDQ-- 294
Cdd:cd09074   142 LAAGQEEVE--RRNQDYRDILSKLKFYRGDP--AIDSIFDHDVVFWFGDLNYRIDSTDDEVRKLISQGDLDDLLEKDQlk 217
                         250       260       270       280       290       300       310       320
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1063699537 295 -------IFRGWQEGIVKFAPTYKYVPNSDLYYgcitykKDEKKRAPAWCDRIIW---YGNGLKQHEYTR-GETKISDHR 363
Cdd:cd09074   218 kqkekgkVFDGFQELPITFPPTYKFDPGTDEYD------TSDKKRIPAWCDRILYkskAGSEIQPLSYTSvPLYKTSDHK 291

                  ....*..
gi 1063699537 364 PVKAIFT 370
Cdd:cd09074   292 PVRATFR 298
INPP5c_ScInp51p-like cd09090
Catalytic inositol polyphosphate 5-phosphatase (INPP5c) domain of Saccharomyces cerevisiae ...
59-369 2.52e-78

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: 243.79  E-value: 2.52e-78
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1063699537  59 KVFVSTWNVGGIVPDDglDMEDLL--ETHKTPCDIYVLGFQEVVPLRASNVLGSDNNKVSTkWNSLIRDALNKRARPHrd 136
Cdd:cd09090     2 NIFVGTFNVNGKSYKD--DLSSWLfpEENDELPDIVVIGLQEVVELTAGQILNSDPSKSSF-WEKKIKTTLNGRGGEK-- 76
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1063699537 137 edlseskgingisqdFRCIISKQMVGILITVWVRGDLWPYIRYPSVSCVGCGIMGCLGNKGSVSVRFQLHETTFCFVCSH 216
Cdd:cd09090    77 ---------------YVLLRSEQLVGTALLFFVKESQLPKVKNVEGSTKKTGLGGMSGNKGAVAIRFDYGDTSFCFVTSH 141
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1063699537 217 LASGGRDRDERqrNSDVNEILARSSFPRGssldlpKKILDHDRVIFLGDLNYRISLPEEKTRLLVESKKWNILLENDQI- 295
Cdd:cd09090   142 LAAGLTNYEER--NNDYKTIARGLRFSRG------RTIKDHDHVIWLGDFNYRISLTNEDVRRFILNGKLDKLLEYDQLn 213
                         250       260       270       280       290       300       310       320
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1063699537 296 --------FRGWQEGIVKFAPTYKYVPNSDlyygciTYKKDEKKRAPAWCDRIIWYGNGLKQHEYTRGETKISDHRPVKA 367
Cdd:cd09090   214 qqmnagevFPGFSEGPITFPPTYKYDKGTD------NYDTSEKQRIPAWTDRILYRGENLRQLSYNSAPLRFSDHRPVYA 287

                  ..
gi 1063699537 368 IF 369
Cdd:cd09090   288 TF 289
IPPc smart00128
Inositol polyphosphate phosphatase, catalytic domain homologues; Mg(2+)-dependent/Li(+) ...
57-376 1.53e-74

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


Pssm-ID: 214525 [Multi-domain]  Cd Length: 306  Bit Score: 234.56  E-value: 1.53e-74
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1063699537   57 NYKVFVSTWNVGG------IVPDDGLDMEDLLETHKTpcDIYVLGFQEVVPLRASNVLGSDNNKVSTkWNSLIRDALNKR 130
Cdd:smart00128   2 DIKVLIGTWNVGGlespkvDVTSWLFQKIEVKQSEKP--DIYVIGLQEVVGLAPGVILETIAGKERL-WSDLLESSLNGD 78
                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1063699537  131 ArphrdedlseskgingisqDFRCIISKQMVGILITVWVRGDLWPYIRYPSVSCVGCGIMGCLGNKGSVSVRFQLHETTF 210
Cdd:smart00128  79 G-------------------QYNVLAKVYLVGILVLVFVKANHLVYIKDVETFTVKTGMGGLWGNKGAVAVRFKLSDTSF 139
                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1063699537  211 CFVCSHLASGGRDRDerQRNSDVNEILARSSFPRGSSLDlpkkILDHDRVIFLGDLNYRISLP-EEKTRLLVESKKWNIL 289
Cdd:smart00128 140 CFVNSHLAAGASNVE--QRNQDYKTILRALSFPERALLS----QFDHDVVFWFGDLNFRLDSPsYEEVRRKISKKEFDDL 213
                          250       260       270       280       290       300       310       320
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1063699537  290 LENDQ---------IFRGWQEGIVKFAPTYKYVP-NSDlyygciTYKKDEKKRAPAWCDRIIW----YGNGLKQHEYTRG 355
Cdd:smart00128 214 LEKDQlnrqreagkVFKGFQEGPITFPPTYKYDSvGTE------TYDTSEKKRVPAWCDRILYrsngPELIQLSEYHSGM 287
                          330       340
                   ....*....|....*....|.
gi 1063699537  356 ETKISDHRPVKAIFttEITVT 376
Cdd:smart00128 288 EITTSDHKPVFATF--RLKVT 306
INPP5c_Synj cd09089
Catalytic inositol polyphosphate 5-phosphatase (INPP5c) domain of synaptojanins; This ...
59-369 2.99e-74

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: 234.59  E-value: 2.99e-74
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1063699537  59 KVFVSTWNVGG------------IVPDDGLDMEDLL-------ETHKTPCDIYVLGFQEVVPLRASNVLG--SDNNKVst 117
Cdd:cd09089     2 RVFVGTWNVNGgkhfrsiafkhqSMTDWLLDNPKLAgqcsndsEEDEKPVDIFAIGFEEMVDLNASNIVSasTTNQKE-- 79
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1063699537 118 kWNSLIRDALNKrarphrdedlseskgingiSQDFRCIISKQMVGILITVWVRGDLWPYIRYPSVSCVGCGIMGCLGNKG 197
Cdd:cd09089    80 -WGEELQKTISR-------------------DHKYVLLTSEQLVGVCLFVFVRPQHAPFIRDVAVDTVKTGLGGAAGNKG 139
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1063699537 198 SVSVRFQLHETTFCFVCSHLASGGRDRDErqRNSDVNEILARSSFPRGSSLDlpkkilDHDRVIFLGDLNYRISLPEEKT 277
Cdd:cd09089   140 AVAIRFLLHSTSLCFVCSHFAAGQSQVKE--RNEDFAEIARKLSFPMGRTLD------SHDYVFWCGDFNYRIDLPNDEV 211
                         250       260       270       280       290       300       310       320
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1063699537 278 RLLVESKKWNILLENDQ---------IFRGWQEGIVKFAPTYKYvpnsDLYygCITYKKDEKKRAPAWCDRIIW------ 342
Cdd:cd09089   212 KELVRNGDWLKLLEFDQltkqkaagnVFKGFLEGEINFAPTYKY----DLF--SDDYDTSEKCRTPAWTDRVLWrrrkwp 285
                         330       340       350       360
                  ....*....|....*....|....*....|....*....|.
gi 1063699537 343 --YGNGLKQHE------------YTRGETKISDHRPVKAIF 369
Cdd:cd09089   286 sdKTEESLVETndptwnpgtllyYGRAELKTSDHRPVVAII 326
COG5411 COG5411
Phosphatidylinositol 5-phosphate phosphatase [Signal transduction mechanisms];
38-381 1.95e-60

Phosphatidylinositol 5-phosphate phosphatase [Signal transduction mechanisms];


Pssm-ID: 227698 [Multi-domain]  Cd Length: 460  Bit Score: 202.71  E-value: 1.95e-60
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1063699537  38 LADERSKSILHNqhkttllNYKVFVSTWNVGGIVPDDglDMEDLL----ETHKTPcDIYVLGFQEVVPLRASNVLGSDNN 113
Cdd:COG5411    17 LRQRRSKYVIEK-------DVSIFVSTFNPPGKPPKA--STKRWLfpeiEATELA-DLYVVGLQEVVELTPGSILSADPY 86
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1063699537 114 KVSTKWNSLIRDALNKrarPHRDEDLSeskgingisqdfrCIISKQMVGILITVWVRGDLWPYIRYPSVSCVGCGIMGCL 193
Cdd:COG5411    87 DRLRIWESKVLDCLNG---AQSDEKYS-------------LLRSPQLGGILLRVFSLATNLPVVKPVSGTVKKTGFGGSS 150
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1063699537 194 GNKGSVSVRFQLHETTFCFVCSHLASGGRDRDERQrnSDVNEILARSSFPRGssldlpKKILDHDRVIFLGDLNYRISLP 273
Cdd:COG5411   151 SNKGAVAIRFNYERTSFCFVNSHLAAGVNNIEERI--FDYRSIASNICFSRG------LRIYDHDTIFWLGDLNYRVTST 222
                         250       260       270       280       290       300       310       320
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1063699537 274 EEKTRLLVESKKWNI--LLENDQI---------FRGWQEGIVKFAPTYKYVPNSDLYYgcitykKDEKKRAPAWCDRIIW 342
Cdd:COG5411   223 NEEVRPEIASDDGRLdkLFEYDQLlwemevgnvFPGFKEPVITFPPTYKFDYGTDEYD------TSDKGRIPSWTDRILY 296
                         330       340       350       360
                  ....*....|....*....|....*....|....*....|
gi 1063699537 343 YGNGLKQHEYTRGET-KISDHRPVKAIFTTEITVTRRGKK 381
Cdd:COG5411   297 KSEQLTPHSYSSIPHlMISDHRPVYATFRAKIKVVDPSKK 336
INPP5c_Synj1 cd09098
Catalytic inositol polyphosphate 5-phosphatase (INPP5c) domain of synaptojanin 1; This ...
59-368 1.28e-58

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: 194.49  E-value: 1.28e-58
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1063699537  59 KVFVSTWNVGG------------IVPDDGLDMEDLLETHK------TPCDIYVLGFQEVVPLRASNVLGSdnnkvSTKWN 120
Cdd:cd09098     2 RVCVGTWNVNGgkqfrsiafknqTLTDWLLDAPKKAGIPEfqdvrsKPVDIFAIGFEEMVELNAGNIVSA-----STTNQ 76
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1063699537 121 SLIRDALNKRarphrdedlseskgingISQDFRCII--SKQMVGILITVWVRGDLWPYIRYPSVSCVGCGIMGCLGNKGS 198
Cdd:cd09098    77 KLWAAELQKT-----------------ISRDQKYVLlaSEQLVGVCLFVFIRPQHAPFIRDVAVDTVKTGMGGATGNKGA 139
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1063699537 199 VSVRFQLHETTFCFVCSHLASGgrDRDERQRNSDVNEILARSSFPRGssldlpKKILDHDRVIFLGDLNYRISLPEEKTR 278
Cdd:cd09098   140 VAIRMLFHTTSLCFVCSHFAAG--QSQVKERNEDFIEIARKLSFPMG------RMLFSHDYVFWCGDFNYRIDIPNEEVK 211
                         250       260       270       280       290       300       310       320
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1063699537 279 LLVESKKWNILLEND---------QIFRGWQEGIVKFAPTYKYVPNSDlyygciTYKKDEKKRAPAWCDRIIW------- 342
Cdd:cd09098   212 ELIRQQNWDSLIAGDqlinqknagQVFRGFLEGKLDFAPTYKYDLFSD------DYDTSEKCRTPAWTDRVLWrrrkwpf 285
                         330       340       350       360
                  ....*....|....*....|....*....|....*....|....*....
gi 1063699537 343 -----------------------YGNGLKQHeYTRGETKISDHRPVKAI 368
Cdd:cd09098   286 drsaedldllnasfpdnskeqytWSPGTLLH-YGRAELKTSDHRPVVAL 333
INPP5c_INPP5J-like cd09094
Catalytic inositol polyphosphate 5-phosphatase (INPP5c) domain of inositol polyphosphate ...
58-370 1.25e-57

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: 190.66  E-value: 1.25e-57
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1063699537  58 YKVFVSTWNVGGIVPDDglDMEDLL---ETHKTPcDIYVLGFQEV--VPL-RASNVLGSDnnkvstKWNSLIRDALNKra 131
Cdd:cd09094     1 LRVYVVTWNVATAPPPI--DVRSLLglqSPEVAP-DIYIIGLQEVnsKPVqFVSDLIFDD------PWSDLFMDILSP-- 69
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1063699537 132 rphrdedlseskgingisQDFRCIISKQMVGILITVWVRGDLWPYIRYPSVSCVGCGIMGCLGNKGSVSVRFQLHETTFC 211
Cdd:cd09094    70 ------------------KGYVKVSSIRLQGLLLLVFVKIQHLPFIRDVQTNYTRTGLGGYWGNKGAVTVRFSLYGHMIC 131
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1063699537 212 FVCSHLASggRDRDERQRNSDVNEILARSSFPRgsslDLPKKILDHDRVIFLGDLNYRIS-LPEEKTRLLVESKKWNILL 290
Cdd:cd09094   132 FLNCHLPA--HMEKWEQRIDDFETILSTQVFNE----CNTPSILDHDYVFWFGDLNFRIEdVSIEFVRELVNSKKYHLLL 205
                         250       260       270       280       290       300       310       320
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1063699537 291 ENDQ---------IFRGWQEGIVKFAPTYKYVPNSDlyygciTYKKDEKKRAPAWCDRIIWYGNGLKQHE---------- 351
Cdd:cd09094   206 EKDQlnmakrkeeAFQGFQEGPLNFAPTYKFDLGTD------EYDTSGKKRKPAWTDRILWKVNPDASTEekflsitqts 279
                         330       340
                  ....*....|....*....|
gi 1063699537 352 YT-RGETKISDHRPVKAIFT 370
Cdd:cd09094   280 YKsHMEYGISDHKPVTAQFR 299
INPP5c_Synj2 cd09099
Catalytic inositol polyphosphate 5-phosphatase (INPP5c) domain of synaptojanin 2; This ...
59-368 2.96e-57

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: 2.96e-57
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1063699537  59 KVFVSTWNVGG------------IVPDDGLD------MEDLLETHKTPCDIYVLGFQEVVPLRASNVLGSD--NNKVstk 118
Cdd:cd09099     2 RVAMGTWNVNGgkqfrsnilgtsELTDWLLDspklsgTPDFQDDESNPPDIFAVGFEEMVELSAGNIVNASttNRKM--- 78
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1063699537 119 WNSLIRDALnkrARPHRdedlseskgingisqdFRCIISKQMVGILITVWVRGDLWPYIRYPSVSCVGCGIMGCLGNKGS 198
Cdd:cd09099    79 WGEQLQKAI---SRSHR----------------YILLTSAQLVGVCLFIFVRPYHVPFIRDVAIDTVKTGMGGKAGNKGA 139
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1063699537 199 VSVRFQLHETTFCFVCSHLASGgrDRDERQRNSDVNEILARSSFPRGssldlpKKILDHDRVIFLGDLNYRISLPEEKTR 278
Cdd:cd09099   140 VAIRFQFYSTSFCFICSHLTAG--QNQVKERNEDYKEITQKLSFPMG------RNVFSHDYVFWCGDFNYRIDLTYEEVF 211
                         250       260       270       280       290       300       310       320
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1063699537 279 LLVESKKWNILLENDQ---------IFRGWQEGIVKFAPTYKYvpnsDLyyGCITYKKDEKKRAPAWCDRIIWY------ 343
Cdd:cd09099   212 YFIKRQDWKKLLEFDQlqlqkssgkIFKDFHEGTINFGPTYKY----DV--GSEAYDTSDKCRTPAWTDRVLWWrkkwpf 285
                         330       340       350       360
                  ....*....|....*....|....*....|....*....|....*...
gi 1063699537 344 ---------------GNGLKQHEYT--------RGETKISDHRPVKAI 368
Cdd:cd09099   286 ektageinlldsdldFDTKIRHTWTpgalmyygRAELQASDHRPVLAI 333
INPP5c_INPP5E-like cd09095
Catalytic inositol polyphosphate 5-phosphatase (INPP5c) domain of Inositol ...
57-369 1.60e-32

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: 124.46  E-value: 1.60e-32
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1063699537  57 NYKVFVSTWNVGGI--VPDDgLDmEDLLETHKTPC-DIYVLGFQEVVPLRasnvlgsdnnkvsTKWnsLIRdalnkrarp 133
Cdd:cd09095     4 NVGIFVATWNMQGQkeLPEN-LD-DFLLPTSADFAqDIYVIGVQEGCSDR-------------REW--EIR--------- 57
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1063699537 134 hrdedLSESKGINGIsqdfrcIISKQMVGIL-ITVWVRGDLWPYIRYPSVSCVGCGIMGCLGNKGSVSVRFQLHETTFCF 212
Cdd:cd09095    58 -----LQETLGPSHV------LLHSASHGVLhLAVFIRRDLIWFCSEVESATVTTRIVSQIKTKGALAISFTFFGTSFLF 126
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1063699537 213 VCSHLASGgrDRDERQRNSDVNEILARSSFPRgsslDLPKKILDH---------DRVIFLGDLNYRISLPEEKTRLLVES 283
Cdd:cd09095   127 ITSHFTSG--DGKVKERVLDYNKIIQALNLPR----NVPTNPYKSesgdvttrfDEVFWFGDFNFRLSGPRHLVDALINQ 200
                         250       260       270       280       290       300       310       320
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1063699537 284 KK---WNILLENDQ---------IFRGWQEGIVKFAPTYKYVPNSDlyygciTYKKDEKKRAPAWCDRIIW---YGNGLK 348
Cdd:cd09095   201 GQevdVSALLQHDQltremskgsIFKGFQEAPIHFPPTYKFDIGSD------VYDTSSKQRVPSYTDRILYrsrQKGDVC 274
                         330       340
                  ....*....|....*....|..
gi 1063699537 349 QHEYTRGET-KISDHRPVKAIF 369
Cdd:cd09095   275 CLKYNSCPSiKTSDHRPVFALF 296
INPP5c_SHIP cd09091
Catalytic inositol polyphosphate 5-phosphatase (INPP5c) domain of SH2 domain containing ...
60-369 1.74e-27

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: 110.81  E-value: 1.74e-27
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1063699537  60 VFVSTWNVGGIVPDD-----------GLDMEDLLEThkTPCDIYVLGFQEvvplrasnvlgsdnNKVSTK-WNSLIRDAL 127
Cdd:cd09091     3 IFIGTWNMGSAPPPKnitswftskgqGKTRDDVADY--IPHDIYVIGTQE--------------DPLGEKeWLDLLRHSL 66
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1063699537 128 NKRArphrdedlseskgingiSQDFRCIISKQMVGILITVWVRGDLWPYIRYPSVSCVGCGIMGCLGNKGSVSVRFQLHE 207
Cdd:cd09091    67 KELT-----------------SLDYKPIAMQTLWNIRIVVLAKPEHENRISHVCTSSVKTGIANTLGNKGAVGVSFMFNG 129
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1063699537 208 TTFCFVCSHLASGGRDRDERQRNS-DVNEILARSSfPRGSSLDLPKKIldhDRVIFLGDLNYRISLPEEKTRLLVESKKW 286
Cdd:cd09091   130 TSFGFVNSHLTSGSEKKLRRNQNYlNILRFLSLGD-KKLSAFNITHRF---THLFWLGDLNYRLDLPIQEAENIIQKIEQ 205
                         250       260       270       280       290       300       310       320
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1063699537 287 NI---LLENDQ---------IFRGWQEGIVKFAPTYKYVPNSDLYYgCITYKKDE--KKRAPAWCDRIIWYG----NGLK 348
Cdd:cd09091   206 QQfepLLRHDQlnlereehkVFLRFSEEEITFPPTYRYERGSRDTY-AYTKQKATgvKYNLPSWCDRILWKSypetHIIC 284
                         330       340
                  ....*....|....*....|.
gi 1063699537 349 QHEYTRGETKISDHRPVKAIF 369
Cdd:cd09091   285 QSYGCTDDIVTSDHSPVFGTF 305
INPP5c_SHIP2-INPPL1 cd09101
Catalytic inositol polyphosphate 5-phosphatase (INPP5c) domain of SH2 domain containing ...
60-369 2.64e-26

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: 107.37  E-value: 2.64e-26
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1063699537  60 VFVSTWNVGGIVPDDGLDM--------EDLLETHKT-PCDIYVLGFQEvvplrasnvlgsdNNKVSTKWNSLIRDALNKR 130
Cdd:cd09101     3 IFIGTWNMGSVPPPKSLASwltsrglgKTLDETTVTiPHDIYVFGTQE-------------NSVGDREWVDFLRASLKEL 69
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1063699537 131 arphrdedlseskgingISQDFRCIISKQMVGILITVWVRGDLWPYIRYPSVSCVGCGIMGCLGNKGSVSVRFQLHETTF 210
Cdd:cd09101    70 -----------------TDIDYQPIALQCLWNIKMVVLVKPEHENRISHVHTSSVKTGIANTLGNKGAVGVSFMFNGTSF 132
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1063699537 211 CFVCSHLASGGRDRDERQRN-SDVNEILARSSfPRGSSLDLPkkiLDHDRVIFLGDLNYRISLPEEKTRLLVESKKWNIL 289
Cdd:cd09101   133 GFVNCHLTSGNEKTHRRNQNyLDILRSLSLGD-KQLNAFDIS---LRFTHLFWFGDLNYRLDMDIQEILNYITRKEFDPL 208
                         250       260       270       280       290       300       310       320
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1063699537 290 LENDQ---------IFRGWQEGIVKFAPTYKYVPNSDLYYGCITYKKDE-KKRAPAWCDRIIWygnglKQHEYTR----- 354
Cdd:cd09101   209 LAVDQlnlereknkVFLRFREEEISFPPTYRYERGSRDTYMWQKQKTTGmRTNVPSWCDRILW-----KSYPETHivcns 283
                         330
                  ....*....|....*....
gi 1063699537 355 ----GETKISDHRPVKAIF 369
Cdd:cd09101   284 ygctDDIVTSDHSPVFGTF 302
INPP5c_SHIP1-INPP5D cd09100
Catalytic inositol polyphosphate 5-phosphatase (INPP5c) domain of SH2 domain containing ...
60-369 1.11e-24

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: 103.14  E-value: 1.11e-24
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1063699537  60 VFVSTWNVGGIVP-----------------DDGLDMedllethkTPCDIYVLGFQEvvplrasNVLGSdnnkvsTKWNSL 122
Cdd:cd09100     3 IFIGTWNMGNAPPpkkitswfqckgqgktrDDTADY--------IPHDIYVIGTQE-------DPLGE------KEWLDT 61
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1063699537 123 IRDALnkrarphrdedlsesKGINGISqdFRCIISKQMVGILITVWVRGDLWPYIRYPSVSCVGCGIMGCLGNKGSVSVR 202
Cdd:cd09100    62 LKHSL---------------REITSIS--FKVIAIQTLWNIRIVVLAKPEHENRISHICTDSVKTGIANTLGNKGAVGVS 124
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1063699537 203 FQLHETTFCFVCSHLASGGRDRDERQRN-SDVNEILARSSfPRGSSLDLPKKIldhDRVIFLGDLNYRISLPEEKTRLLV 281
Cdd:cd09100   125 FMFNGTSFGFVNSHLTSGSEKKLRRNQNyFNILRFLVLGD-KKLSPFNITHRF---THLFWLGDLNYRVELPNTEAENII 200
                         250       260       270       280       290       300       310       320
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1063699537 282 E---SKKWNILLENDQ---------IFRGWQEGIVKFAPTYKYVPNSDLYYgCITYKKDE--KKRAPAWCDRIIWYGNGL 347
Cdd:cd09100   201 QkikQQQYQELLPHDQllierkeskVFLQFEEEEITFAPTYRFERGTRERY-AYTKQKATgmKYNLPSWCDRVLWKSYPL 279
                         330       340
                  ....*....|....*....|....*.
gi 1063699537 348 K----QHEYTRGETKISDHRPVKAIF 369
Cdd:cd09100   280 VhvvcQSYGCTDDITTSDHSPVFATF 305
EEP cd08372
Exonuclease-Endonuclease-Phosphatase (EEP) domain superfamily; This large superfamily includes ...
62-367 2.26e-05

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: 45.55  E-value: 2.26e-05
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1063699537  62 VSTWNVGGivpDDGLDMEDLLETHKTPCDIYVLGFQEVVPLRASNVLGSDNNKVSTKWNSLIRDALNKRARphrdedlse 141
Cdd:cd08372     1 VASYNVNG---LNAATRASGIARWVRELDPDIVCLQEVKDSQYSAVALNQLLPEGYHQYQSGPSRKEGYEG--------- 68
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1063699537 142 skgingisqdfrciiskqmVGILItvwvrgdLWPYIRyPSVSCVGCGIMGCLGNKGSVSVRFQLHETTFCFVCSHLASGG 221
Cdd:cd08372    69 -------------------VAILS-------KTPKFK-IVEKHQYKFGEGDSGERRAVVVKFDVHDKELCVVNAHLQAGG 121
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1063699537 222 RDRDERqrnsdVNEILARSSFPRGSSLDLpkkildHDRVIFLGDLNYRISLPEEKTRllveskkwnillendqifRGWQE 301
Cdd:cd08372   122 TRADVR-----DAQLKEVLEFLKRLRQPN------SAPVVICGDFNVRPSEVDSENP------------------SSMLR 172
                         250       260       270       280       290       300       310
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 1063699537 302 GIVKFAptykyvpNSDLYYGCI---TYKKDeKKRAPAWCDRIIwYGNGLKQH--------EYTRGETkISDHRPVKA 367
Cdd:cd08372   173 LFVALN-------LVDSFETLPhayTFDTY-MHNVKSRLDYIF-VSKSLLPSvksskilsDAARARI-PSDHYPIEV 239
 
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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