NCBI Home Page NCBI Site Search page NCBI Guide that lists and describes the NCBI resources
Conserved domains on  [gi|805751813|ref|XP_012144122|]
View 

PREDICTED: 72 kDa inositol polyphosphate 5-phosphatase isoform X2 [Megachile rotundata]

Protein Classification

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

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

Graphical summary

 Zoom to residue level

show extra options »

Show site features     Horizontal zoom: ×

List of domain hits

 Name Accession Description Interval E-value
EEP super family cl00490
Exonuclease-Endonuclease-Phosphatase (EEP) domain superfamily; This large superfamily includes ...
 140-451 1.09e-154

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 cd09095:

Pssm-ID: 469791  Cd Length: 298  Bit Score: 442.25  E-value: 1.09e-154
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 805751813 140 PNRELKIFIGTWNMNGQ-SPPKELNDFMLPSDIETVPDLLAIGTQESCSERNEWEAALQETLGPSHVLLSSTSLGTLHLA 218
Cdd:cd09095    1 PDRNVGIFVATWNMQGQkELPENLDDFLLPTSADFAQDIYVIGVQEGCSDRREWEIRLQETLGPSHVLLHSASHGVLHLA 80

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 805751813 219 LFLRRDLIWFCSIAEDASFSTRTGTAFRTKGAVAIALMLFGTSFLFVTAHLTAHQDKVKERIHDIKRIVRNLDLPKDLPT 298
Cdd:cd09095   81 VFIRRDLIWFCSEVESATVTTRIVSQIKTKGALAISFTFFGTSFLFITSHFTSGDGKVKERVLDYNKIIQALNLPRNVPT 160

                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 805751813 299 ---KHKSKDVTQNFDCVFWCGDLNFRLTQPREEVIQWVADTCFPQQSPInLHKDQLRTILNEGAVLRGFEEAPITFPPTY 375
Cdd:cd09095  161 npyKSESGDVTTRFDEVFWFGDFNFRLSGPRHLVDALINQGQEVDVSAL-LQHDQLTREMSKGSIFKGFQEAPIHFPPTY 239

                        250       260       270       280       290       300       310
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 805751813 376 KYDPGTQIFDSSSKQRTPAYTDRILFKgkghtkayirrvshessSSYKDGIIeCLVYDSVPSICTSDHKPVWGVFK 451
Cdd:cd09095  240 KFDIGSDVYDTSSKQRVPSYTDRILYR-----------------SRQKGDVC-CLKYNSCPSIKTSDHRPVFALFR 297
 
Name Accession Description Interval E-value
INPP5c_INPP5E-like cd09095
Catalytic inositol polyphosphate 5-phosphatase (INPP5c) domain of Inositol ...
 140-451 1.09e-154

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: 442.25  E-value: 1.09e-154
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 805751813 140 PNRELKIFIGTWNMNGQ-SPPKELNDFMLPSDIETVPDLLAIGTQESCSERNEWEAALQETLGPSHVLLSSTSLGTLHLA 218
Cdd:cd09095    1 PDRNVGIFVATWNMQGQkELPENLDDFLLPTSADFAQDIYVIGVQEGCSDRREWEIRLQETLGPSHVLLHSASHGVLHLA 80

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 805751813 219 LFLRRDLIWFCSIAEDASFSTRTGTAFRTKGAVAIALMLFGTSFLFVTAHLTAHQDKVKERIHDIKRIVRNLDLPKDLPT 298
Cdd:cd09095   81 VFIRRDLIWFCSEVESATVTTRIVSQIKTKGALAISFTFFGTSFLFITSHFTSGDGKVKERVLDYNKIIQALNLPRNVPT 160

                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 805751813 299 ---KHKSKDVTQNFDCVFWCGDLNFRLTQPREEVIQWVADTCFPQQSPInLHKDQLRTILNEGAVLRGFEEAPITFPPTY 375
Cdd:cd09095  161 npyKSESGDVTTRFDEVFWFGDFNFRLSGPRHLVDALINQGQEVDVSAL-LQHDQLTREMSKGSIFKGFQEAPIHFPPTY 239

                        250       260       270       280       290       300       310
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 805751813 376 KYDPGTQIFDSSSKQRTPAYTDRILFKgkghtkayirrvshessSSYKDGIIeCLVYDSVPSICTSDHKPVWGVFK 451
Cdd:cd09095  240 KFDIGSDVYDTSSKQRVPSYTDRILYR-----------------SRQKGDVC-CLKYNSCPSIKTSDHRPVFALFR 297
IPPc smart00128
Inositol polyphosphate phosphatase, catalytic domain homologues; Mg(2+)-dependent/Li(+) ...
 142-454 5.28e-68

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


Pssm-ID: 214525 [Multi-domain]  Cd Length: 306  Bit Score: 220.30  E-value: 5.28e-68
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 805751813   142 RELKIFIGTWNMNGQSPPKELNDFMLPSDIETV----PDLLAIGTQE-------SCSERN-----EWEAALQETLGPS-- 203
Cdd:smart00128   1 RDIKVLIGTWNVGGLESPKVDVTSWLFQKIEVKqsekPDIYVIGLQEvvglapgVILETIagkerLWSDLLESSLNGDgq 80

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 805751813   204 HVLLSSTSLGTLHLALFLRRDLIWFcsIAEDASFSTRTGTAF--RTKGAVAIALMLFGTSFLFVTAHLTAHQDKVKERIH 281
Cdd:smart00128  81 YNVLAKVYLVGILVLVFVKANHLVY--IKDVETFTVKTGMGGlwGNKGAVAVRFKLSDTSFCFVNSHLAAGASNVEQRNQ 158

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 805751813   282 DIKRIVRNLDLPKDLPTKHKSKDVtqnfdcVFWCGDLNFRLTQPREEVIQwvaDTCFPQQSPINLHKDQLRTILNEGAVL 361
Cdd:smart00128 159 DYKTILRALSFPERALLSQFDHDV------VFWFGDLNFRLDSPSYEEVR---RKISKKEFDDLLEKDQLNRQREAGKVF 229

                          250       260       270       280       290       300       310       320
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 805751813   362 RGFEEAPITFPPTYKYDP-GTQIFDSSSKQRTPAYTDRILFKgkghtkayirrvshessSSYKDGIIEClVYDSVPSICT 440
Cdd:smart00128 230 KGFQEGPITFPPTYKYDSvGTETYDTSEKKRVPAWCDRILYR-----------------SNGPELIQLS-EYHSGMEITT 291

                          330
                   ....*....|....
gi 805751813   441 SDHKPVWGVFKTTV 454
Cdd:smart00128 292 SDHKPVFATFRLKV 305
COG5411 COG5411
Phosphatidylinositol 5-phosphate phosphatase [Signal transduction mechanisms];
132-486 2.23e-51

Phosphatidylinositol 5-phosphate phosphatase [Signal transduction mechanisms];


Pssm-ID: 227698 [Multi-domain]  Cd Length: 460  Bit Score: 181.13  E-value: 2.23e-51
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 805751813 132 PVELEKVLPNR-----ELKIFIGTWNMNGQSPPKELNDFMLPSDIETV-PDLLAIGTQE----------SCSERNEWEAA 195
Cdd:COG5411   13 IVAVLRQRRSKyviekDVSIFVSTFNPPGKPPKASTKRWLFPEIEATElADLYVVGLQEvveltpgsilSADPYDRLRIW 92

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 805751813 196 LQETL--------GPSHVLLSSTSLGTLHLALFLRRDLIwfcSIAEDASFSTR-TGTAFRT--KGAVAIALMLFGTSFLF 264
Cdd:COG5411   93 ESKVLdclngaqsDEKYSLLRSPQLGGILLRVFSLATNL---PVVKPVSGTVKkTGFGGSSsnKGAVAIRFNYERTSFCF 169

                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 805751813 265 VTAHLTAHQDKVKERIHDIKRIVRNLDLPKDLPTKHKskdvtqnfDCVFWCGDLNFRLTQPREEVIQWVA-DTCFPQQsp 343
Cdd:COG5411  170 VNSHLAAGVNNIEERIFDYRSIASNICFSRGLRIYDH--------DTIFWLGDLNYRVTSTNEEVRPEIAsDDGRLDK-- 239

                        250       260       270       280       290       300       310       320
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 805751813 344 iNLHKDQLRTILNEGAVLRGFEEAPITFPPTYKYDPGTQIFDSSSKQRTPAYTDRILFKGKghtkayirrVSHESSssyk 423
Cdd:COG5411  240 -LFEYDQLLWEMEVGNVFPGFKEPVITFPPTYKFDYGTDEYDTSDKGRIPSWTDRILYKSE---------QLTPHS---- 305

                        330       340       350       360       370       380
                 ....*....|....*....|....*....|....*....|....*....|....*....|...
gi 805751813 424 dgiieclvYDSVPSICTSDHKPVWGVFKTTVRPGiDTIPLSGglFNREVYLEGIKRRAAAMDE 486
Cdd:COG5411  306 --------YSSIPHLMISDHRPVYATFRAKIKVV-DPSKKEG--LIEKLYAEYKTELGEAGDI 357
PLN03191 PLN03191
Type I inositol-1,4,5-trisphosphate 5-phosphatase 2; Provisional
 248-454 5.43e-24

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


Pssm-ID: 215624 [Multi-domain]  Cd Length: 621  Bit Score: 105.37  E-value: 5.43e-24
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 805751813 248 KGAVAIALMLFGTSFLFVTAHLTA-HQDKVKERIH-DIKRIVR--------NLDLPKDLPTKhkskdvtqnfDCVFWCGD 317
Cdd:PLN03191 408 KGSVSISMSLFQSRLCFVCSHLTSgHKDGAEQRRNaDVYEIIRrtrfssvlDTDQPQTIPSH----------DQIFWFGD 477

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 805751813 318 LNFRLTQPREEVIQWVADTCFPQQspINlhKDQLRTILNEGAVLRGFEEAPITFPPTYKYDPGTQIF-----DSSSKQRT 392
Cdd:PLN03191 478 LNYRLNMLDTEVRKLVAQKRWDEL--IN--SDQLIKELRSGHVFDGWKEGPIKFPPTYKYEINSDRYvgenpKEGEKKRS 553

                        170       180       190       200       210       220
                 ....*....|....*....|....*....|....*....|....*....|....*....|..
gi 805751813 393 PAYTDRILFKGKGhtkayIRRVSHESSssykdgiieclvydsvpSICTSDHKPVWGVFKTTV 454
Cdd:PLN03191 554 PAWCDRILWLGKG-----IKQLCYKRS-----------------EIRLSDHRPVSSMFLVEV 593
 
Name Accession Description Interval E-value
INPP5c_INPP5E-like cd09095
Catalytic inositol polyphosphate 5-phosphatase (INPP5c) domain of Inositol ...
 140-451 1.09e-154

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: 442.25  E-value: 1.09e-154
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 805751813 140 PNRELKIFIGTWNMNGQ-SPPKELNDFMLPSDIETVPDLLAIGTQESCSERNEWEAALQETLGPSHVLLSSTSLGTLHLA 218
Cdd:cd09095    1 PDRNVGIFVATWNMQGQkELPENLDDFLLPTSADFAQDIYVIGVQEGCSDRREWEIRLQETLGPSHVLLHSASHGVLHLA 80

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 805751813 219 LFLRRDLIWFCSIAEDASFSTRTGTAFRTKGAVAIALMLFGTSFLFVTAHLTAHQDKVKERIHDIKRIVRNLDLPKDLPT 298
Cdd:cd09095   81 VFIRRDLIWFCSEVESATVTTRIVSQIKTKGALAISFTFFGTSFLFITSHFTSGDGKVKERVLDYNKIIQALNLPRNVPT 160

                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 805751813 299 ---KHKSKDVTQNFDCVFWCGDLNFRLTQPREEVIQWVADTCFPQQSPInLHKDQLRTILNEGAVLRGFEEAPITFPPTY 375
Cdd:cd09095  161 npyKSESGDVTTRFDEVFWFGDFNFRLSGPRHLVDALINQGQEVDVSAL-LQHDQLTREMSKGSIFKGFQEAPIHFPPTY 239

                        250       260       270       280       290       300       310
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 805751813 376 KYDPGTQIFDSSSKQRTPAYTDRILFKgkghtkayirrvshessSSYKDGIIeCLVYDSVPSICTSDHKPVWGVFK 451
Cdd:cd09095  240 KFDIGSDVYDTSSKQRVPSYTDRILYR-----------------SRQKGDVC-CLKYNSCPSIKTSDHRPVFALFR 297
INPP5c cd09074
Catalytic domain of inositol polyphosphate 5-phosphatases; Inositol polyphosphate ...
 144-451 1.76e-87

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: 270.36  E-value: 1.76e-87
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 805751813 144 LKIFIGTWNMNGQSPPKELNDFMLPSDIETVPDLLAIGTQESC------------SERNEWEAALQETLGPSH--VLLSS 209
Cdd:cd09074    1 VKIFVVTWNVGGGISPPENLENWLSPKGTEAPDIYAVGVQEVDmsvqgfvgnddsAKAREWVDNIQEALNEKEnyVLLGS 80

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 805751813 210 TSLGTLHLALFLRRDLIWFCSIAEDASFSTRTGTAFRT--KGAVAIALMLFGTSFLFVTAHLTAHQDKVKERIHDIKRIV 287
Cdd:cd09074   81 AQLVGIFLFVFVKKEHLPQIKDLEVEGVTVGTGGGGKLgnKGGVAIRFQINDTSFCFVNSHLAAGQEEVERRNQDYRDIL 160

                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 805751813 288 RNLDLPKDLPtkhkSKDVTQNFDCVFWCGDLNFRLTQPREEVIQWVADTCFPQQspinLHKDQLRTILNEGAVLRGFEEA 367
Cdd:cd09074  161 SKLKFYRGDP----AIDSIFDHDVVFWFGDLNYRIDSTDDEVRKLISQGDLDDL----LEKDQLKKQKEKGKVFDGFQEL 232

                        250       260       270       280       290       300       310       320
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 805751813 368 PITFPPTYKYDPGTQIFDSSSKQRTPAYTDRILFKgkghtkayirrvshesssSYKDGIIECLVYDSVPSICTSDHKPVW 447
Cdd:cd09074  233 PITFPPTYKFDPGTDEYDTSDKKRIPAWCDRILYK------------------SKAGSEIQPLSYTSVPLYKTSDHKPVR 294


                 ....
gi 805751813 448 GVFK 451
Cdd:cd09074  295 ATFR 298
INPP5c_ScInp51p-like cd09090
Catalytic inositol polyphosphate 5-phosphatase (INPP5c) domain of Saccharomyces cerevisiae ...
 144-451 8.46e-73

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: 232.23  E-value: 8.46e-73
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 805751813 144 LKIFIGTWNMNGQSPPKELNDFMLPSDIETVPDLLAIGTQE------------SCSERNEWEAALQETL----GPSHVLL 207
Cdd:cd09090    1 INIFVGTFNVNGKSYKDDLSSWLFPEENDELPDIVVIGLQEvveltagqilnsDPSKSSFWEKKIKTTLngrgGEKYVLL 80

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 805751813 208 SSTSLGTLHLALFLRRDLIWFCSIAEDASFSTRTGTAFRTKGAVAIALMLFGTSFLFVTAHLTAHQDKVKERIHDIKRIV 287
Cdd:cd09090   81 RSEQLVGTALLFFVKESQLPKVKNVEGSTKKTGLGGMSGNKGAVAIRFDYGDTSFCFVTSHLAAGLTNYEERNNDYKTIA 160

                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 805751813 288 RNLDLPKDLPTKHKskdvtqnfDCVFWCGDLNFRLTQPREEVIQWVADTCFPQQspinLHKDQLRTILNEGAVLRGFEEA 367
Cdd:cd09090  161 RGLRFSRGRTIKDH--------DHVIWLGDFNYRISLTNEDVRRFILNGKLDKL----LEYDQLNQQMNAGEVFPGFSEG 228

                        250       260       270       280       290       300       310       320
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 805751813 368 PITFPPTYKYDPGTQIFDSSSKQRTPAYTDRILFKGKghtkaYIRRVShessssykdgiieclvYDSVPSIcTSDHKPVW 447
Cdd:cd09090  229 PITFPPTYKYDKGTDNYDTSEKQRIPAWTDRILYRGE-----NLRQLS----------------YNSAPLR-FSDHRPVY 286


                 ....
gi 805751813 448 GVFK 451
Cdd:cd09090  287 ATFE 290
IPPc smart00128
Inositol polyphosphate phosphatase, catalytic domain homologues; Mg(2+)-dependent/Li(+) ...
 142-454 5.28e-68

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


Pssm-ID: 214525 [Multi-domain]  Cd Length: 306  Bit Score: 220.30  E-value: 5.28e-68
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 805751813   142 RELKIFIGTWNMNGQSPPKELNDFMLPSDIETV----PDLLAIGTQE-------SCSERN-----EWEAALQETLGPS-- 203
Cdd:smart00128   1 RDIKVLIGTWNVGGLESPKVDVTSWLFQKIEVKqsekPDIYVIGLQEvvglapgVILETIagkerLWSDLLESSLNGDgq 80

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 805751813   204 HVLLSSTSLGTLHLALFLRRDLIWFcsIAEDASFSTRTGTAF--RTKGAVAIALMLFGTSFLFVTAHLTAHQDKVKERIH 281
Cdd:smart00128  81 YNVLAKVYLVGILVLVFVKANHLVY--IKDVETFTVKTGMGGlwGNKGAVAVRFKLSDTSFCFVNSHLAAGASNVEQRNQ 158

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 805751813   282 DIKRIVRNLDLPKDLPTKHKSKDVtqnfdcVFWCGDLNFRLTQPREEVIQwvaDTCFPQQSPINLHKDQLRTILNEGAVL 361
Cdd:smart00128 159 DYKTILRALSFPERALLSQFDHDV------VFWFGDLNFRLDSPSYEEVR---RKISKKEFDDLLEKDQLNRQREAGKVF 229

                          250       260       270       280       290       300       310       320
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 805751813   362 RGFEEAPITFPPTYKYDP-GTQIFDSSSKQRTPAYTDRILFKgkghtkayirrvshessSSYKDGIIEClVYDSVPSICT 440
Cdd:smart00128 230 KGFQEGPITFPPTYKYDSvGTETYDTSEKKRVPAWCDRILYR-----------------SNGPELIQLS-EYHSGMEITT 291

                          330
                   ....*....|....
gi 805751813   441 SDHKPVWGVFKTTV 454
Cdd:smart00128 292 SDHKPVFATFRLKV 305
INPP5c_INPP5B cd09093
Catalytic inositol polyphosphate 5-phosphatase (INPP5c) domain of Type II inositol ...
 144-451 1.04e-62

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: 206.01  E-value: 1.04e-62
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 805751813 144 LKIFIGTWNMNGQSPPKELNDFMLPSdiETVPDLLAIGTQE-----------SCSERNEWEAALQETLGP--SHVLLSST 210
Cdd:cd09093    1 FRIFVGTWNVNGQSPDESLRPWLSCD--EEPPDIYAIGFQEldlsaeaflfnDSSREQEWVKAVERGLHPdaKYKKVKLI 78

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 805751813 211 SLGTLHLALFLRRDLIWFcsIAEDASFSTRTGTAFRT--KGAVAIALMLFGTSFLFVTAHLTAHQDKVKERIHDIKRIVR 288
Cdd:cd09093   79 RLVGMMLLVFVKKEHRQH--IKEVAAETVGTGIMGKMgnKGGVAVRFQFHNTTFCFVNSHLAAHMEEVERRNQDYKDICA 156

                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 805751813 289 NLDLPKDLPTKHKSKDvtqnFDCVFWCGDLNFRLTQ-PREEVIQWVADtcfpQQSPINLHKDQLRTILNEGAVLRGFEEA 367
Cdd:cd09093  157 RMKFEDPDGPPLSISD----HDVVFWLGDLNYRIQElPTEEVKELIEK----NDLEELLKYDQLNIQRRAGKVFEGFTEG 228

                        250       260       270       280       290       300       310       320
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 805751813 368 PITFPPTYKYDPGTQIFDSSSKQRTPAYTDRILFKGKGhtkayirrvshessssykdgiIECLVYDSVPSICTSDHKPVW 447
Cdd:cd09093  229 EINFIPTYKYDPGTDNWDSSEKCRAPAWCDRILWRGTN---------------------IVQLSYRSHMELKTSDHKPVS 287


                 ....
gi 805751813 448 GVFK 451
Cdd:cd09093  288 ALFD 291
INPP5c_INPP5J-like cd09094
Catalytic inositol polyphosphate 5-phosphatase (INPP5c) domain of inositol polyphosphate ...
 144-450 1.01e-59

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: 198.75  E-value: 1.01e-59
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 805751813 144 LKIFIGTWNMNGQSPPKELNDFMLPSDIETVPDLLAIGTQESCSERNE----------WEAALQETLGPSH-VLLSSTSL 212
Cdd:cd09094    1 LRVYVVTWNVATAPPPIDVRSLLGLQSPEVAPDIYIIGLQEVNSKPVQfvsdlifddpWSDLFMDILSPKGyVKVSSIRL 80

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 805751813 213 GTLHLALFLRRDLIWFCSIAeDASFsTRTGTA--FRTKGAVAIALMLFGTSFLFVTAHLTAHQDKVKERIHDIKRIVRNL 290
Cdd:cd09094   81 QGLLLLVFVKIQHLPFIRDV-QTNY-TRTGLGgyWGNKGAVTVRFSLYGHMICFLNCHLPAHMEKWEQRIDDFETILSTQ 158

                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 805751813 291 DLPKDLPTKHKSKDVtqnfdcVFWCGDLNFRLTQ-PREEVIQWVAdtcfPQQSPINLHKDQLRTILNEGAVLRGFEEAPI 369
Cdd:cd09094  159 VFNECNTPSILDHDY------VFWFGDLNFRIEDvSIEFVRELVN----SKKYHLLLEKDQLNMAKRKEEAFQGFQEGPL 228

                        250       260       270       280       290       300       310       320
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 805751813 370 TFPPTYKYDPGTQIFDSSSKQRTPAYTDRILFKgkghtkayirrVSHESSSSYKDGIIECLVYDSVPSICTSDHKPVWGV 449
Cdd:cd09094  229 NFAPTYKFDLGTDEYDTSGKKRKPAWTDRILWK-----------VNPDASTEEKFLSITQTSYKSHMEYGISDHKPVTAQ 297


                 .
gi 805751813 450 F 450
Cdd:cd09094  298 F 298
INPP5c_Synj cd09089
Catalytic inositol polyphosphate 5-phosphatase (INPP5c) domain of synaptojanins; This ...
 144-451 1.45e-59

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: 199.15  E-value: 1.45e-59
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 805751813 144 LKIFIGTWNMNGQS-------PPKELNDFML------------PSDIETVPDLLAIGTQE------------SCSERNEW 192
Cdd:cd09089    1 LRVFVGTWNVNGGKhfrsiafKHQSMTDWLLdnpklagqcsndSEEDEKPVDIFAIGFEEmvdlnasnivsaSTTNQKEW 80

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 805751813 193 EAALQETLGPSH--VLLSSTSLGTLHLALFLRRDLIWFCSIAEDASFSTRTGTAFRTKGAVAIALMLFGTSFLFVTAHLT 270
Cdd:cd09089   81 GEELQKTISRDHkyVLLTSEQLVGVCLFVFVRPQHAPFIRDVAVDTVKTGLGGAAGNKGAVAIRFLLHSTSLCFVCSHFA 160

                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 805751813 271 AHQDKVKERIHDIKRIVRNLDLPKDlpTKHKSKDVtqnfdcVFWCGDLNFRLTQPREEVIQWVADTCFPQQspinLHKDQ 350
Cdd:cd09089  161 AGQSQVKERNEDFAEIARKLSFPMG--RTLDSHDY------VFWCGDFNYRIDLPNDEVKELVRNGDWLKL----LEFDQ 228

                        250       260       270       280       290       300       310       320
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 805751813 351 LRTILNEGAVLRGFEEAPITFPPTYKYDPGTQIFDSSSKQRTPAYTDRILFKGKGHTKAYIRRV-SHESSSSYKDGIiec 429
Cdd:cd09089  229 LTKQKAAGNVFKGFLEGEINFAPTYKYDLFSDDYDTSEKCRTPAWTDRVLWRRRKWPSDKTEESlVETNDPTWNPGT--- 305

                        330       340
                 ....*....|....*....|..
gi 805751813 430 LVYDSVPSICTSDHKPVWGVFK 451
Cdd:cd09089  306 LLYYGRAELKTSDHRPVVAIID 327
COG5411 COG5411
Phosphatidylinositol 5-phosphate phosphatase [Signal transduction mechanisms];
132-486 2.23e-51

Phosphatidylinositol 5-phosphate phosphatase [Signal transduction mechanisms];


Pssm-ID: 227698 [Multi-domain]  Cd Length: 460  Bit Score: 181.13  E-value: 2.23e-51
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 805751813 132 PVELEKVLPNR-----ELKIFIGTWNMNGQSPPKELNDFMLPSDIETV-PDLLAIGTQE----------SCSERNEWEAA 195
Cdd:COG5411   13 IVAVLRQRRSKyviekDVSIFVSTFNPPGKPPKASTKRWLFPEIEATElADLYVVGLQEvveltpgsilSADPYDRLRIW 92

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 805751813 196 LQETL--------GPSHVLLSSTSLGTLHLALFLRRDLIwfcSIAEDASFSTR-TGTAFRT--KGAVAIALMLFGTSFLF 264
Cdd:COG5411   93 ESKVLdclngaqsDEKYSLLRSPQLGGILLRVFSLATNL---PVVKPVSGTVKkTGFGGSSsnKGAVAIRFNYERTSFCF 169

                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 805751813 265 VTAHLTAHQDKVKERIHDIKRIVRNLDLPKDLPTKHKskdvtqnfDCVFWCGDLNFRLTQPREEVIQWVA-DTCFPQQsp 343
Cdd:COG5411  170 VNSHLAAGVNNIEERIFDYRSIASNICFSRGLRIYDH--------DTIFWLGDLNYRVTSTNEEVRPEIAsDDGRLDK-- 239

                        250       260       270       280       290       300       310       320
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 805751813 344 iNLHKDQLRTILNEGAVLRGFEEAPITFPPTYKYDPGTQIFDSSSKQRTPAYTDRILFKGKghtkayirrVSHESSssyk 423
Cdd:COG5411  240 -LFEYDQLLWEMEVGNVFPGFKEPVITFPPTYKFDYGTDEYDTSDKGRIPSWTDRILYKSE---------QLTPHS---- 305

                        330       340       350       360       370       380
                 ....*....|....*....|....*....|....*....|....*....|....*....|...
gi 805751813 424 dgiieclvYDSVPSICTSDHKPVWGVFKTTVRPGiDTIPLSGglFNREVYLEGIKRRAAAMDE 486
Cdd:COG5411  306 --------YSSIPHLMISDHRPVYATFRAKIKVV-DPSKKEG--LIEKLYAEYKTELGEAGDI 357
INPP5c_Synj2 cd09099
Catalytic inositol polyphosphate 5-phosphatase (INPP5c) domain of synaptojanin 2; This ...
 144-449 5.34e-46

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: 163.65  E-value: 5.34e-46
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 805751813 144 LKIFIGTWNMNGQSP-------PKELNDFMLPS-----------DIETVPDLLAIGTQE------------SCSERNEWE 193
Cdd:cd09099    1 TRVAMGTWNVNGGKQfrsnilgTSELTDWLLDSpklsgtpdfqdDESNPPDIFAVGFEEmvelsagnivnaSTTNRKMWG 80

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 805751813 194 AALQETLGPSH--VLLSSTSLGTLHLALFLRRDLIWFcsIAEDASFSTRTGTAFRT--KGAVAIALMLFGTSFLFVTAHL 269
Cdd:cd09099   81 EQLQKAISRSHryILLTSAQLVGVCLFIFVRPYHVPF--IRDVAIDTVKTGMGGKAgnKGAVAIRFQFYSTSFCFICSHL 158

                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 805751813 270 TAHQDKVKERIHDIKRIVRNLDLPKdlptkhkSKDVTQNfDCVFWCGDLNFRLTQPREEVIQWVADtcfpQQSPINLHKD 349
Cdd:cd09099  159 TAGQNQVKERNEDYKEITQKLSFPM-------GRNVFSH-DYVFWCGDFNYRIDLTYEEVFYFIKR----QDWKKLLEFD 226

                        250       260       270       280       290       300       310       320
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 805751813 350 QLRTILNEGAVLRGFEEAPITFPPTYKYDPGTQIFDSSSKQRTPAYTDRILFKGKGHT-KAYIRRVSHESSSSYKDGIIE 428
Cdd:cd09099  227 QLQLQKSSGKIFKDFHEGTINFGPTYKYDVGSEAYDTSDKCRTPAWTDRVLWWRKKWPfEKTAGEINLLDSDLDFDTKIR 306

                        330       340
                 ....*....|....*....|....*..
gi 805751813 429 ------CLVYDSVPSICTSDHKPVWGV 449
Cdd:cd09099  307 htwtpgALMYYGRAELQASDHRPVLAI 333
INPP5c_Synj1 cd09098
Catalytic inositol polyphosphate 5-phosphatase (INPP5c) domain of synaptojanin 1; This ...
 144-446 4.64e-43

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: 155.58  E-value: 4.64e-43
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 805751813 144 LKIFIGTWNMNGQSPPKE-------LNDFML--PS--------DIETVP-DLLAIGTQE----------SCSERNE--WE 193
Cdd:cd09098    1 IRVCVGTWNVNGGKQFRSiafknqtLTDWLLdaPKkagipefqDVRSKPvDIFAIGFEEmvelnagnivSASTTNQklWA 80

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 805751813 194 AALQETLGPS--HVLLSSTSLGTLHLALFLRRDLIWFCSIAEDASFSTRTGTAFRTKGAVAIALMLFGTSFLFVTAHLTA 271
Cdd:cd09098   81 AELQKTISRDqkYVLLASEQLVGVCLFVFIRPQHAPFIRDVAVDTVKTGMGGATGNKGAVAIRMLFHTTSLCFVCSHFAA 160

                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 805751813 272 HQDKVKERIHDIKRIVRNLDLPKDlptkhkskDVTQNFDCVFWCGDLNFRLTQPREEVIQWVAdtcfpQQSPINL-HKDQ 350
Cdd:cd09098  161 GQSQVKERNEDFIEIARKLSFPMG--------RMLFSHDYVFWCGDFNYRIDIPNEEVKELIR-----QQNWDSLiAGDQ 227

                        250       260       270       280       290       300       310       320
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 805751813 351 LRTILNEGAVLRGFEEAPITFPPTYKYDPGTQIFDSSSKQRTPAYTDRILFKGKghtKAYIRRVSHE---SSSSYKDGII 427
Cdd:cd09098  228 LINQKNAGQVFRGFLEGKLDFAPTYKYDLFSDDYDTSEKCRTPAWTDRVLWRRR---KWPFDRSAEDldlLNASFPDNSK 304

                        330       340
                 ....*....|....*....|....*.
gi 805751813 428 E-------CLVYDSVPSICTSDHKPV 446
Cdd:cd09098  305 EqytwspgTLLHYGRAELKTSDHRPV 330
INPP5c_SHIP cd09091
Catalytic inositol polyphosphate 5-phosphatase (INPP5c) domain of SH2 domain containing ...
 144-451 3.26e-41

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: 149.71  E-value: 3.26e-41
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 805751813 144 LKIFIGTWNMNGQSPPKELNDFMLPSDI--------ETVP-DLLAIGTQESCSERNEW----EAALQETLGPSHVLLSST 210
Cdd:cd09091    1 ISIFIGTWNMGSAPPPKNITSWFTSKGQgktrddvaDYIPhDIYVIGTQEDPLGEKEWldllRHSLKELTSLDYKPIAMQ 80

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 805751813 211 SLGTLHLALFLRRDliWFCSIAEDASFSTRTGTA--FRTKGAVAIALMLFGTSFLFVTAHLTAHQDKVKERIHDIKRIVR 288
Cdd:cd09091   81 TLWNIRIVVLAKPE--HENRISHVCTSSVKTGIAntLGNKGAVGVSFMFNGTSFGFVNSHLTSGSEKKLRRNQNYLNILR 158

                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 805751813 289 NLDLPKdlpTKHKSKDVTQNFDCVFWCGDLNFRLTQPREEVIQWVADTCFPQQSPInLHKDQLRTILNEGAVLRGFEEAP 368
Cdd:cd09091  159 FLSLGD---KKLSAFNITHRFTHLFWLGDLNYRLDLPIQEAENIIQKIEQQQFEPL-LRHDQLNLEREEHKVFLRFSEEE 234

                        250       260       270       280       290       300       310       320
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 805751813 369 ITFPPTYKYDPGTQIFDSSSKQRT-------PAYTDRILFKgkghtkayirrvshesssSYKDGIIECLVYDSVPSICTS 441
Cdd:cd09091  235 ITFPPTYRYERGSRDTYAYTKQKAtgvkynlPSWCDRILWK------------------SYPETHIICQSYGCTDDIVTS 296

                        330
                 ....*....|
gi 805751813 442 DHKPVWGVFK 451
Cdd:cd09091  297 DHSPVFGTFE 306
INPP5c_SHIP1-INPP5D cd09100
Catalytic inositol polyphosphate 5-phosphatase (INPP5c) domain of SH2 domain containing ...
 144-451 1.66e-40

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: 147.82  E-value: 1.66e-40
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 805751813 144 LKIFIGTWNMNGQSPPKELNDFML--------PSDIETVP-DLLAIGTQESCSERNEW----EAALQETLGPSHVLLSST 210
Cdd:cd09100    1 ITIFIGTWNMGNAPPPKKITSWFQckgqgktrDDTADYIPhDIYVIGTQEDPLGEKEWldtlKHSLREITSISFKVIAIQ 80

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 805751813 211 SLGTLHLALFLRRDliWFCSIAEDASFSTRTGTA--FRTKGAVAIALMLFGTSFLFVTAHLTAHQDKVKERIHDIKRIVR 288
Cdd:cd09100   81 TLWNIRIVVLAKPE--HENRISHICTDSVKTGIAntLGNKGAVGVSFMFNGTSFGFVNSHLTSGSEKKLRRNQNYFNILR 158

                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 805751813 289 NLDLPKdlpTKHKSKDVTQNFDCVFWCGDLNFRLTQPR---EEVIQWVADtcfpQQSPINLHKDQLRTILNEGAVLRGFE 365
Cdd:cd09100  159 FLVLGD---KKLSPFNITHRFTHLFWLGDLNYRVELPNteaENIIQKIKQ----QQYQELLPHDQLLIERKESKVFLQFE 231

                        250       260       270       280       290       300       310       320
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 805751813 366 EAPITFPPTYKYDPGTQIFDSSSKQRT-------PAYTDRILFKgkghtkayirrvshesssSYKDGIIECLVYDSVPSI 438
Cdd:cd09100  232 EEEITFAPTYRFERGTRERYAYTKQKAtgmkynlPSWCDRVLWK------------------SYPLVHVVCQSYGCTDDI 293

                        330
                 ....*....|...
gi 805751813 439 CTSDHKPVWGVFK 451
Cdd:cd09100  294 TTSDHSPVFATFE 306
INPP5c_SHIP2-INPPL1 cd09101
Catalytic inositol polyphosphate 5-phosphatase (INPP5c) domain of SH2 domain containing ...
 144-451 1.71e-37

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: 139.72  E-value: 1.71e-37
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 805751813 144 LKIFIGTWNMNGQSPPKELNDFMLPSDI--------ETVP-DLLAIGTQESCSERNEW----EAALQETLGPSHVLLSST 210
Cdd:cd09101    1 ISIFIGTWNMGSVPPPKSLASWLTSRGLgktldettVTIPhDIYVFGTQENSVGDREWvdflRASLKELTDIDYQPIALQ 80

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 805751813 211 SLGTLHLALFLRRDLIWFCSIAEDASFSTRTGTAFRTKGAVAIALMLFGTSFLFVTAHLTAHQDKVKERIHDIKRIVRNL 290
Cdd:cd09101   81 CLWNIKMVVLVKPEHENRISHVHTSSVKTGIANTLGNKGAVGVSFMFNGTSFGFVNCHLTSGNEKTHRRNQNYLDILRSL 160

                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 805751813 291 DL-PKDLptkhKSKDVTQNFDCVFWCGDLNFRLTQPREEVIQWVADTCFpqqSPInLHKDQLRTILNEGAVLRGFEEAPI 369
Cdd:cd09101  161 SLgDKQL----NAFDISLRFTHLFWFGDLNYRLDMDIQEILNYITRKEF---DPL-LAVDQLNLEREKNKVFLRFREEEI 232

                        250       260       270       280       290       300       310       320
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 805751813 370 TFPPTYKYDPGTQIFDSSSKQRT-------PAYTDRILFKgkghtkayirrvshesssSYKDGIIECLVYDSVPSICTSD 442
Cdd:cd09101  233 SFPPTYRYERGSRDTYMWQKQKTtgmrtnvPSWCDRILWK------------------SYPETHIVCNSYGCTDDIVTSD 294


                 ....*....
gi 805751813 443 HKPVWGVFK 451
Cdd:cd09101  295 HSPVFGTFE 303
PLN03191 PLN03191
Type I inositol-1,4,5-trisphosphate 5-phosphatase 2; Provisional
 248-454 5.43e-24

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


Pssm-ID: 215624 [Multi-domain]  Cd Length: 621  Bit Score: 105.37  E-value: 5.43e-24
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 805751813 248 KGAVAIALMLFGTSFLFVTAHLTA-HQDKVKERIH-DIKRIVR--------NLDLPKDLPTKhkskdvtqnfDCVFWCGD 317
Cdd:PLN03191 408 KGSVSISMSLFQSRLCFVCSHLTSgHKDGAEQRRNaDVYEIIRrtrfssvlDTDQPQTIPSH----------DQIFWFGD 477

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 805751813 318 LNFRLTQPREEVIQWVADTCFPQQspINlhKDQLRTILNEGAVLRGFEEAPITFPPTYKYDPGTQIF-----DSSSKQRT 392
Cdd:PLN03191 478 LNYRLNMLDTEVRKLVAQKRWDEL--IN--SDQLIKELRSGHVFDGWKEGPIKFPPTYKYEINSDRYvgenpKEGEKKRS 553

                        170       180       190       200       210       220
                 ....*....|....*....|....*....|....*....|....*....|....*....|..
gi 805751813 393 PAYTDRILFKGKGhtkayIRRVSHESSssykdgiieclvydsvpSICTSDHKPVWGVFKTTV 454
Cdd:PLN03191 554 PAWCDRILWLGKG-----IKQLCYKRS-----------------EIRLSDHRPVSSMFLVEV 593
EEP cd08372
Exonuclease-Endonuclease-Phosphatase (EEP) domain superfamily; This large superfamily includes ...
 148-446 3.16e-07

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: 51.33  E-value: 3.16e-07
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 805751813 148 IGTWNMNGqsppkeLNDFMLPSDI-----ETVPDLLAIgtQESCSERNEWEAALQETLGPSHVLLS--STSLGTLHLALF 220
Cdd:cd08372    1 VASYNVNG------LNAATRASGIarwvrELDPDIVCL--QEVKDSQYSAVALNQLLPEGYHQYQSgpSRKEGYEGVAIL 72

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 805751813 221 LRRDLIwfcSIAEDASFSTRTGTAFrTKGAVAIALMLFGTSFLFVTAHLTAHQDKVKERIHDIKRI---VRNLDLPKDLP 297
Cdd:cd08372   73 SKTPKF---KIVEKHQYKFGEGDSG-ERRAVVVKFDVHDKELCVVNAHLQAGGTRADVRDAQLKEVlefLKRLRQPNSAP 148

                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 805751813 298 tkhkskdvtqnfdcVFWCGDLNFRltqpreeviqwvadtcfpqqsPINLHKDQLRTiLNEGAVLRGFEEAPITFPPTYKY 377
Cdd:cd08372  149 --------------VVICGDFNVR---------------------PSEVDSENPSS-MLRLFVALNLVDSFETLPHAYTF 192

                        250       260       270       280       290       300       310
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 805751813 378 DpgtqifdsSSKQRTPAYTDRILFKGkghtkayirrvSHESS-SSYKdgiiecLVYDSVPSICTSDHKPV 446
Cdd:cd08372  193 D--------TYMHNVKSRLDYIFVSK-----------SLLPSvKSSK------ILSDAARARIPSDHYPI 237
INPP5A cd09092
Type I inositol polyphosphate 5-phosphatase I; Type I inositol polyphosphate 5-phosphatase I ...
 366-451 1.06e-06

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: 50.93  E-value: 1.06e-06
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 805751813 366 EAPITFPPTYKY--DP--GTQIFDSsskqRTPAYTDRILFKgkgHTKAYIRRVSHESSssykdgiiecLVYDSV-PSICT 440
Cdd:cd09092  309 ELDISFPPSYPYseDPeqGTQYMNT----RCPAWCDRILMS---HSARELKSENEEKS----------VTYDMIgPNVCM 371

                         90
                 ....*....|.
gi 805751813 441 SDHKPVWGVFK 451
Cdd:cd09092  372 GDHKPVFLTFR 382
 
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.
Help | Disclaimer | Write to the Help Desk
NCBI | NLM | NIH