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Conserved domains on  [gi|1370471300|ref|XP_024306570|]
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inositol polyphosphate 5-phosphatase K isoform X1 [Homo sapiens]

Protein Classification

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 ...
 1-244 9.21e-115

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 cd09094:

Pssm-ID: 469791  Cd Length: 300  Bit Score: 335.88  E-value: 9.21e-115
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370471300   1 MDVLSPLSFIKVSHVRMQGILLLVFAKYQHLPYIQILSTKSTPTGLFGYWGNKGGVNICLKLYGYYVSIINCHLPPHISN 80
Cdd:cd09094    64 MDILSPKGYVKVSSIRLQGLLLLVFVKIQHLPFIRDVQTNYTRTGLGGYWGNKGAVTVRFSLYGHMICFLNCHLPAHMEK 143

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370471300  81 NYQRLEHFDRILEMQNCEGRDIPNILDHDLIIWFGDMNFRIEDFGLHFVRESIKNRCYGGLWEKDQLSIAKKHDPLLREF 160
Cdd:cd09094   144 WEQRIDDFETILSTQVFNECNTPSILDHDYVFWFGDLNFRIEDVSIEFVRELVNSKKYHLLLEKDQLNMAKRKEEAFQGF 223

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370471300 161 QEGRLLFPPTYKFDRNSNDYDTSEKKRKPAWTDRILWRLKrqpcagpdtpiPPASHF----SLSLRGYSSHMTYGISDHK 236
Cdd:cd09094   224 QEGPLNFAPTYKFDLGTDEYDTSGKKRKPAWTDRILWKVN-----------PDASTEekflSITQTSYKSHMEYGISDHK 292


                  ....*...
gi 1370471300 237 PVSGTFDL 244
Cdd:cd09094   293 PVTAQFRL 300
SKICH pfam17751
SKICH domain; The SKICH domains of SKIP and PIPP mediate plasma membrane localization. The ...
 255-355 2.30e-37

SKICH domain; The SKICH domains of SKIP and PIPP mediate plasma membrane localization. The functions of the SKICH domains of NDP52 and CALCOCO1 are not known.


:

Pssm-ID: 465482  Cd Length: 102  Bit Score: 130.06  E-value: 2.30e-37
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370471300 255 IVLMPEDLWTV-ENDMMVSYSSTSDFPSSPWDWIGLYKVGLRDVNDYVSYAWVGDSKVSCSDNLNQVYIDISNIP-TTED 332
Cdd:pfam17751   1 VVFQNVGEWYPpDEDIECSYTLTPDFTPSSWDWIGLFKVGWKSVNDYVTYVWAKDDEVEGSNSVRQVLFKASYLPkEPEG 80

                          90       100
                  ....*....|....*....|...
gi 1370471300 333 EFLLCYYSNSLrSVVGISRPFQI 355
Cdd:pfam17751  81 FYQFCYVSNLG-SVVGISTPFQF 102
 
Name Accession Description Interval E-value
INPP5c_INPP5J-like cd09094
Catalytic inositol polyphosphate 5-phosphatase (INPP5c) domain of inositol polyphosphate ...
 1-244 9.21e-115

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: 335.88  E-value: 9.21e-115
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370471300   1 MDVLSPLSFIKVSHVRMQGILLLVFAKYQHLPYIQILSTKSTPTGLFGYWGNKGGVNICLKLYGYYVSIINCHLPPHISN 80
Cdd:cd09094    64 MDILSPKGYVKVSSIRLQGLLLLVFVKIQHLPFIRDVQTNYTRTGLGGYWGNKGAVTVRFSLYGHMICFLNCHLPAHMEK 143

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370471300  81 NYQRLEHFDRILEMQNCEGRDIPNILDHDLIIWFGDMNFRIEDFGLHFVRESIKNRCYGGLWEKDQLSIAKKHDPLLREF 160
Cdd:cd09094   144 WEQRIDDFETILSTQVFNECNTPSILDHDYVFWFGDLNFRIEDVSIEFVRELVNSKKYHLLLEKDQLNMAKRKEEAFQGF 223

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370471300 161 QEGRLLFPPTYKFDRNSNDYDTSEKKRKPAWTDRILWRLKrqpcagpdtpiPPASHF----SLSLRGYSSHMTYGISDHK 236
Cdd:cd09094   224 QEGPLNFAPTYKFDLGTDEYDTSGKKRKPAWTDRILWKVN-----------PDASTEekflSITQTSYKSHMEYGISDHK 292


                  ....*...
gi 1370471300 237 PVSGTFDL 244
Cdd:cd09094   293 PVTAQFRL 300
IPPc smart00128
Inositol polyphosphate phosphatase, catalytic domain homologues; Mg(2+)-dependent/Li(+) ...
 9-247 5.18e-89

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


Pssm-ID: 214525 [Multi-domain]  Cd Length: 306  Bit Score: 270.38  E-value: 5.18e-89
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370471300    9 FIKVSHVRMQGILLLVFAKYQHLPYIQILSTKSTPTGLFGYWGNKGGVNICLKLYGYYVSIINCHLPPHISNNYQRLEHF 88
Cdd:smart00128  81 YNVLAKVYLVGILVLVFVKANHLVYIKDVETFTVKTGMGGLWGNKGAVAVRFKLSDTSFCFVNSHLAAGASNVEQRNQDY 160

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370471300   89 DRILEMQNCEGRDIPNILDHDLIIWFGDMNFRIEDFGLHFVRESIKNRCYGGLWEKDQLSIAKKHDPLLREFQEGRLLFP 168
Cdd:smart00128 161 KTILRALSFPERALLSQFDHDVVFWFGDLNFRLDSPSYEEVRRKISKKEFDDLLEKDQLNRQREAGKVFKGFQEGPITFP 240

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370471300  169 PTYKFDR-NSNDYDTSEKKRKPAWTDRILWRLKrqpcaGPDTpippashfsLSLRGYSSHMTYGISDHKPVSGTFDLELK 247
Cdd:smart00128 241 PTYKYDSvGTETYDTSEKKRVPAWCDRILYRSN-----GPEL---------IQLSEYHSGMEITTSDHKPVFATFRLKVT 306
SKICH pfam17751
SKICH domain; The SKICH domains of SKIP and PIPP mediate plasma membrane localization. The ...
 255-355 2.30e-37

SKICH domain; The SKICH domains of SKIP and PIPP mediate plasma membrane localization. The functions of the SKICH domains of NDP52 and CALCOCO1 are not known.


Pssm-ID: 465482  Cd Length: 102  Bit Score: 130.06  E-value: 2.30e-37
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370471300 255 IVLMPEDLWTV-ENDMMVSYSSTSDFPSSPWDWIGLYKVGLRDVNDYVSYAWVGDSKVSCSDNLNQVYIDISNIP-TTED 332
Cdd:pfam17751   1 VVFQNVGEWYPpDEDIECSYTLTPDFTPSSWDWIGLFKVGWKSVNDYVTYVWAKDDEVEGSNSVRQVLFKASYLPkEPEG 80

                          90       100
                  ....*....|....*....|...
gi 1370471300 333 EFLLCYYSNSLrSVVGISRPFQI 355
Cdd:pfam17751  81 FYQFCYVSNLG-SVVGISTPFQF 102
COG5411 COG5411
Phosphatidylinositol 5-phosphate phosphatase [Signal transduction mechanisms];
17-247 3.12e-34

Phosphatidylinositol 5-phosphate phosphatase [Signal transduction mechanisms];


Pssm-ID: 227698 [Multi-domain]  Cd Length: 460  Bit Score: 131.44  E-value: 3.12e-34
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370471300  17 MQGILLLVFAKYQHLPYIQILSTKSTPTGLFGYWGNKGGVNICLKLYGYYVSIINCHLPPHISNNYQRLEHFDRIleMQN 96
Cdd:COG5411   117 LGGILLRVFSLATNLPVVKPVSGTVKKTGFGGSSSNKGAVAIRFNYERTSFCFVNSHLAAGVNNIEERIFDYRSI--ASN 194

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370471300  97 CEGRDIPNILDHDLIIWFGDMNFRIE--DFGLHFVRESIKNRCYGgLWEKDQLSIAKKHDPLLREFQEGRLLFPPTYKFD 174
Cdd:COG5411   195 ICFSRGLRIYDHDTIFWLGDLNYRVTstNEEVRPEIASDDGRLDK-LFEYDQLLWEMEVGNVFPGFKEPVITFPPTYKFD 273

                         170       180       190       200       210       220       230
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|...
gi 1370471300 175 RNSNDYDTSEKKRKPAWTDRILWrlkRQPCAGPDTpippashfslslrgYSSHMTYGISDHKPVSGTFDLELK 247
Cdd:COG5411   274 YGTDEYDTSDKGRIPSWTDRILY---KSEQLTPHS--------------YSSIPHLMISDHRPVYATFRAKIK 329
PLN03191 PLN03191
Type I inositol-1,4,5-trisphosphate 5-phosphatase 2; Provisional
 8-247 7.71e-25

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


Pssm-ID: 215624 [Multi-domain]  Cd Length: 621  Bit Score: 106.14  E-value: 7.71e-25
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370471300   8 SFIKVSHVRMQGILLLVFAKYQHLPYIQILSTKSTPTGLFGYWGNKGGVNICLKLYGYYVSIINCHLPP-HISNNYQRLE 86
Cdd:PLN03191  363 KYVRIVSKQMVGIYVSVWVRKRLRRHINNLKVSPVGVGLMGYMGNKGSVSISMSLFQSRLCFVCSHLTSgHKDGAEQRRN 442

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370471300  87 ----------HFDRILEMQncEGRDIPNildHDLIIWFGDMNFRIEDFGLHfVRESIKNRCYGGLWEKDQLSIAKKHDPL 156
Cdd:PLN03191  443 advyeiirrtRFSSVLDTD--QPQTIPS---HDQIFWFGDLNYRLNMLDTE-VRKLVAQKRWDELINSDQLIKELRSGHV 516

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370471300 157 LREFQEGRLLFPPTYKFDRNSNDY-----DTSEKKRKPAWTDRILWRLK--RQPCagpdtpippasHFSLSLRgysshmt 229
Cdd:PLN03191  517 FDGWKEGPIKFPPTYKYEINSDRYvgenpKEGEKKRSPAWCDRILWLGKgiKQLC-----------YKRSEIR------- 578

                         250
                  ....*....|....*...
gi 1370471300 230 ygISDHKPVSGTFDLELK 247
Cdd:PLN03191  579 --LSDHRPVSSMFLVEVE 594
 
Name Accession Description Interval E-value
INPP5c_INPP5J-like cd09094
Catalytic inositol polyphosphate 5-phosphatase (INPP5c) domain of inositol polyphosphate ...
 1-244 9.21e-115

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: 335.88  E-value: 9.21e-115
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370471300   1 MDVLSPLSFIKVSHVRMQGILLLVFAKYQHLPYIQILSTKSTPTGLFGYWGNKGGVNICLKLYGYYVSIINCHLPPHISN 80
Cdd:cd09094    64 MDILSPKGYVKVSSIRLQGLLLLVFVKIQHLPFIRDVQTNYTRTGLGGYWGNKGAVTVRFSLYGHMICFLNCHLPAHMEK 143

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370471300  81 NYQRLEHFDRILEMQNCEGRDIPNILDHDLIIWFGDMNFRIEDFGLHFVRESIKNRCYGGLWEKDQLSIAKKHDPLLREF 160
Cdd:cd09094   144 WEQRIDDFETILSTQVFNECNTPSILDHDYVFWFGDLNFRIEDVSIEFVRELVNSKKYHLLLEKDQLNMAKRKEEAFQGF 223

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370471300 161 QEGRLLFPPTYKFDRNSNDYDTSEKKRKPAWTDRILWRLKrqpcagpdtpiPPASHF----SLSLRGYSSHMTYGISDHK 236
Cdd:cd09094   224 QEGPLNFAPTYKFDLGTDEYDTSGKKRKPAWTDRILWKVN-----------PDASTEekflSITQTSYKSHMEYGISDHK 292


                  ....*...
gi 1370471300 237 PVSGTFDL 244
Cdd:cd09094   293 PVTAQFRL 300
IPPc smart00128
Inositol polyphosphate phosphatase, catalytic domain homologues; Mg(2+)-dependent/Li(+) ...
 9-247 5.18e-89

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


Pssm-ID: 214525 [Multi-domain]  Cd Length: 306  Bit Score: 270.38  E-value: 5.18e-89
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370471300    9 FIKVSHVRMQGILLLVFAKYQHLPYIQILSTKSTPTGLFGYWGNKGGVNICLKLYGYYVSIINCHLPPHISNNYQRLEHF 88
Cdd:smart00128  81 YNVLAKVYLVGILVLVFVKANHLVYIKDVETFTVKTGMGGLWGNKGAVAVRFKLSDTSFCFVNSHLAAGASNVEQRNQDY 160

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370471300   89 DRILEMQNCEGRDIPNILDHDLIIWFGDMNFRIEDFGLHFVRESIKNRCYGGLWEKDQLSIAKKHDPLLREFQEGRLLFP 168
Cdd:smart00128 161 KTILRALSFPERALLSQFDHDVVFWFGDLNFRLDSPSYEEVRRKISKKEFDDLLEKDQLNRQREAGKVFKGFQEGPITFP 240

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370471300  169 PTYKFDR-NSNDYDTSEKKRKPAWTDRILWRLKrqpcaGPDTpippashfsLSLRGYSSHMTYGISDHKPVSGTFDLELK 247
Cdd:smart00128 241 PTYKYDSvGTETYDTSEKKRVPAWCDRILYRSN-----GPEL---------IQLSEYHSGMEITTSDHKPVFATFRLKVT 306
INPP5c cd09074
Catalytic domain of inositol polyphosphate 5-phosphatases; Inositol polyphosphate ...
 9-244 8.32e-73

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: 228.76  E-value: 8.32e-73
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370471300   9 FIKVSHVRMQGILLLVFAKYQHLPYIQILSTKSTP--TGLFGYWGNKGGVNICLKLYGYYVSIINCHLPPHISNNYQRLE 86
Cdd:cd09074    75 YVLLGSAQLVGIFLFVFVKKEHLPQIKDLEVEGVTvgTGGGGKLGNKGGVAIRFQINDTSFCFVNSHLAAGQEEVERRNQ 154

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370471300  87 HFDRIL-EMQNCEG-RDIPNILDHDLIIWFGDMNFRIEDFGLHfVRESIKNRCYGGLWEKDQLSIAKKHDPLLREFQEGR 164
Cdd:cd09074   155 DYRDILsKLKFYRGdPAIDSIFDHDVVFWFGDLNYRIDSTDDE-VRKLISQGDLDDLLEKDQLKKQKEKGKVFDGFQELP 233

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370471300 165 LLFPPTYKFDRNSNDYDTSEKKRKPAWTDRILWRlkrqPCAGpdTPIPPAShfslslrgYSSHMTYGISDHKPVSGTFDL 244
Cdd:cd09074   234 ITFPPTYKFDPGTDEYDTSDKKRIPAWCDRILYK----SKAG--SEIQPLS--------YTSVPLYKTSDHKPVRATFRV 299
INPP5c_INPP5B cd09093
Catalytic inositol polyphosphate 5-phosphatase (INPP5c) domain of Type II inositol ...
 8-243 7.21e-68

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: 215.64  E-value: 7.21e-68
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370471300   8 SFIKVSHVRMQGILLLVFAKYQHLPYIQILSTKSTPTGLFGYWGNKGGVNICLKLYGYYVSIINCHLPPHISNNYQRLEH 87
Cdd:cd09093    71 KYKKVKLIRLVGMMLLVFVKKEHRQHIKEVAAETVGTGIMGKMGNKGGVAVRFQFHNTTFCFVNSHLAAHMEEVERRNQD 150

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370471300  88 FDRILE-MQNCEGRDIP-NILDHDLIIWFGDMNFRIEDFGLHFVRESIKNRCYGGLWEKDQLSIAKKHDPLLREFQEGRL 165
Cdd:cd09093   151 YKDICArMKFEDPDGPPlSISDHDVVFWLGDLNYRIQELPTEEVKELIEKNDLEELLKYDQLNIQRRAGKVFEGFTEGEI 230

                         170       180       190       200       210       220       230
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 1370471300 166 LFPPTYKFDRNSNDYDTSEKKRKPAWTDRILWRLKRqpcagpdtpippashfsLSLRGYSSHMTYGISDHKPVSGTFD 243
Cdd:cd09093   231 NFIPTYKYDPGTDNWDSSEKCRAPAWCDRILWRGTN-----------------IVQLSYRSHMELKTSDHKPVSALFD 291
INPP5c_Synj cd09089
Catalytic inositol polyphosphate 5-phosphatase (INPP5c) domain of synaptojanins; This ...
 8-243 3.17e-48

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: 166.03  E-value: 3.17e-48
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370471300   8 SFIKVSHVRMQGILLLVFAKYQHLPYIQILSTKSTPTGLFGYWGNKGGVNICLKLYGYYVSIINCHLPPHISNNYQRLEH 87
Cdd:cd09089    93 KYVLLTSEQLVGVCLFVFVRPQHAPFIRDVAVDTVKTGLGGAAGNKGAVAIRFLLHSTSLCFVCSHFAAGQSQVKERNED 172

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370471300  88 FDRIlemqnCEGRDIP---NILDHDLIIWFGDMNFRIeDFGLHFVRESIKNRCYGGLWEKDQLSIAKKHDPLLREFQEGR 164
Cdd:cd09089   173 FAEI-----ARKLSFPmgrTLDSHDYVFWCGDFNYRI-DLPNDEVKELVRNGDWLKLLEFDQLTKQKAAGNVFKGFLEGE 246

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370471300 165 LLFPPTYKFDRNSNDYDTSEKKRKPAWTDRILWRLKRQP-----CAGPDTPIPPASHFSLSLRGYSSHMTygiSDHKPVS 239
Cdd:cd09089   247 INFAPTYKYDLFSDDYDTSEKCRTPAWTDRVLWRRRKWPsdkteESLVETNDPTWNPGTLLYYGRAELKT---SDHRPVV 323


                  ....
gi 1370471300 240 GTFD 243
Cdd:cd09089   324 AIID 327
INPP5c_ScInp51p-like cd09090
Catalytic inositol polyphosphate 5-phosphatase (INPP5c) domain of Saccharomyces cerevisiae ...
 17-242 3.06e-46

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: 159.81  E-value: 3.06e-46
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370471300  17 MQGILLLVFAKYQHLPYIQILSTKSTPTGLFGYWGNKGGVNICLKLYGYYVSIINCHLPPHISNNYQRLEHFDRILE-MQ 95
Cdd:cd09090    85 LVGTALLFFVKESQLPKVKNVEGSTKKTGLGGMSGNKGAVAIRFDYGDTSFCFVTSHLAAGLTNYEERNNDYKTIARgLR 164

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370471300  96 NCEGRDIPnilDHDLIIWFGDMNFRIeDFGLHFVRESIKNRCYGGLWEKDQLSIAKKHDPLLREFQEGRLLFPPTYKFDR 175
Cdd:cd09090   165 FSRGRTIK---DHDHVIWLGDFNYRI-SLTNEDVRRFILNGKLDKLLEYDQLNQQMNAGEVFPGFSEGPITFPPTYKYDK 240

                         170       180       190       200       210       220
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 1370471300 176 NSNDYDTSEKKRKPAWTDRILWRlkrqpcagpdtpippashfSLSLR--GYSSHMTYgISDHKPVSGTF 242
Cdd:cd09090   241 GTDNYDTSEKQRIPAWTDRILYR-------------------GENLRqlSYNSAPLR-FSDHRPVYATF 289
INPP5c_Synj2 cd09099
Catalytic inositol polyphosphate 5-phosphatase (INPP5c) domain of synaptojanin 2; This ...
 9-238 4.54e-38

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: 139.38  E-value: 4.54e-38
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370471300   9 FIKVSHVRMQGILLLVFAKYQHLPYIQILSTKSTPTGLFGYWGNKGGVNICLKLYGYYVSIINCHLPPHISNNYQRLEHF 88
Cdd:cd09099    93 YILLTSAQLVGVCLFIFVRPYHVPFIRDVAIDTVKTGMGGKAGNKGAVAIRFQFYSTSFCFICSHLTAGQNQVKERNEDY 172

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370471300  89 DRILE-MQNCEGRdipNILDHDLIIWFGDMNFRIeDFGLHFVRESIKNRCYGGLWEKDQLSIAKKHDPLLREFQEGRLLF 167
Cdd:cd09099   173 KEITQkLSFPMGR---NVFSHDYVFWCGDFNYRI-DLTYEEVFYFIKRQDWKKLLEFDQLQLQKSSGKIFKDFHEGTINF 248

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370471300 168 PPTYKFDRNSNDYDTSEKKRKPAWTDRILWRLKRQP---CAGPDTPIPPASHFSLSLRGY---SSHMTYG-----ISDHK 236
Cdd:cd09099   249 GPTYKYDVGSEAYDTSDKCRTPAWTDRVLWWRKKWPfekTAGEINLLDSDLDFDTKIRHTwtpGALMYYGraelqASDHR 328


                  ..
gi 1370471300 237 PV 238
Cdd:cd09099   329 PV 330
SKICH pfam17751
SKICH domain; The SKICH domains of SKIP and PIPP mediate plasma membrane localization. The ...
 255-355 2.30e-37

SKICH domain; The SKICH domains of SKIP and PIPP mediate plasma membrane localization. The functions of the SKICH domains of NDP52 and CALCOCO1 are not known.


Pssm-ID: 465482  Cd Length: 102  Bit Score: 130.06  E-value: 2.30e-37
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370471300 255 IVLMPEDLWTV-ENDMMVSYSSTSDFPSSPWDWIGLYKVGLRDVNDYVSYAWVGDSKVSCSDNLNQVYIDISNIP-TTED 332
Cdd:pfam17751   1 VVFQNVGEWYPpDEDIECSYTLTPDFTPSSWDWIGLFKVGWKSVNDYVTYVWAKDDEVEGSNSVRQVLFKASYLPkEPEG 80

                          90       100
                  ....*....|....*....|...
gi 1370471300 333 EFLLCYYSNSLrSVVGISRPFQI 355
Cdd:pfam17751  81 FYQFCYVSNLG-SVVGISTPFQF 102
INPP5c_Synj1 cd09098
Catalytic inositol polyphosphate 5-phosphatase (INPP5c) domain of synaptojanin 1; This ...
 9-244 7.37e-37

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: 136.32  E-value: 7.37e-37
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370471300   9 FIKVSHVRMQGILLLVFAKYQHLPYIQILSTKSTPTGLFGYWGNKGGVNICLKLYGYYVSIINCHLPPHISNNYQRLEHF 88
Cdd:cd09098    93 YVLLASEQLVGVCLFVFIRPQHAPFIRDVAVDTVKTGMGGATGNKGAVAIRMLFHTTSLCFVCSHFAAGQSQVKERNEDF 172

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370471300  89 DRIL-EMQNCEGRdipNILDHDLIIWFGDMNFRIeDFGLHFVRESIKNRCYGGLWEKDQLSIAKKHDPLLREFQEGRLLF 167
Cdd:cd09098   173 IEIArKLSFPMGR---MLFSHDYVFWCGDFNYRI-DIPNEEVKELIRQQNWDSLIAGDQLINQKNAGQVFRGFLEGKLDF 248

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370471300 168 PPTYKFDRNSNDYDTSEKKRKPAWTDRILWRLKRQPC--AGPDTPIPPASHFSLSLRGYS----SHMTYG-----ISDHK 236
Cdd:cd09098   249 APTYKYDLFSDDYDTSEKCRTPAWTDRVLWRRRKWPFdrSAEDLDLLNASFPDNSKEQYTwspgTLLHYGraelkTSDHR 328


                  ....*...
gi 1370471300 237 PVSGTFDL 244
Cdd:cd09098   329 PVVALIDI 336
COG5411 COG5411
Phosphatidylinositol 5-phosphate phosphatase [Signal transduction mechanisms];
17-247 3.12e-34

Phosphatidylinositol 5-phosphate phosphatase [Signal transduction mechanisms];


Pssm-ID: 227698 [Multi-domain]  Cd Length: 460  Bit Score: 131.44  E-value: 3.12e-34
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370471300  17 MQGILLLVFAKYQHLPYIQILSTKSTPTGLFGYWGNKGGVNICLKLYGYYVSIINCHLPPHISNNYQRLEHFDRIleMQN 96
Cdd:COG5411   117 LGGILLRVFSLATNLPVVKPVSGTVKKTGFGGSSSNKGAVAIRFNYERTSFCFVNSHLAAGVNNIEERIFDYRSI--ASN 194

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370471300  97 CEGRDIPNILDHDLIIWFGDMNFRIE--DFGLHFVRESIKNRCYGgLWEKDQLSIAKKHDPLLREFQEGRLLFPPTYKFD 174
Cdd:COG5411   195 ICFSRGLRIYDHDTIFWLGDLNYRVTstNEEVRPEIASDDGRLDK-LFEYDQLLWEMEVGNVFPGFKEPVITFPPTYKFD 273

                         170       180       190       200       210       220       230
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|...
gi 1370471300 175 RNSNDYDTSEKKRKPAWTDRILWrlkRQPCAGPDTpippashfslslrgYSSHMTYGISDHKPVSGTFDLELK 247
Cdd:COG5411   274 YGTDEYDTSDKGRIPSWTDRILY---KSEQLTPHS--------------YSSIPHLMISDHRPVYATFRAKIK 329
INPP5c_INPP5E-like cd09095
Catalytic inositol polyphosphate 5-phosphatase (INPP5c) domain of Inositol ...
 53-244 1.76e-31

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: 120.61  E-value: 1.76e-31
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370471300  53 KGGVNICLKLYGYYVSIINCHLPPHISNNYQRLEHFDRILEMQNCEGRDIPNILDH---------DLIIWFGDMNFRIeD 123
Cdd:cd09095   110 KGALAISFTFFGTSFLFITSHFTSGDGKVKERVLDYNKIIQALNLPRNVPTNPYKSesgdvttrfDEVFWFGDFNFRL-S 188

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370471300 124 FGLHFVRESIKNRC---YGGLWEKDQLSIAKKHDPLLREFQEGRLLFPPTYKFDRNSNDYDTSEKKRKPAWTDRILWRLK 200
Cdd:cd09095   189 GPRHLVDALINQGQevdVSALLQHDQLTREMSKGSIFKGFQEAPIHFPPTYKFDIGSDVYDTSSKQRVPSYTDRILYRSR 268

                         170       180       190       200
                  ....*....|....*....|....*....|....*....|....
gi 1370471300 201 rqpcagPDTPIPPAShfslslrgYSSHMTYGISDHKPVSGTFDL 244
Cdd:cd09095   269 ------QKGDVCCLK--------YNSCPSIKTSDHRPVFALFRV 298
INPP5c_SHIP2-INPPL1 cd09101
Catalytic inositol polyphosphate 5-phosphatase (INPP5c) domain of SH2 domain containing ...
 20-244 2.81e-25

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: 103.90  E-value: 2.81e-25
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370471300  20 ILLLVFAKYQHLPYIQILSTKSTPTGLFGYWGNKGGVNICLKLYGYYVSIINCHLPPHISNNYQRLEHFDRILEMQNCEG 99
Cdd:cd09101    85 IKMVVLVKPEHENRISHVHTSSVKTGIANTLGNKGAVGVSFMFNGTSFGFVNCHLTSGNEKTHRRNQNYLDILRSLSLGD 164

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370471300 100 RDIpNILDHDL----IIWFGDMNFRIeDFGLHFVRESIKNRCYGGLWEKDQLSIAKKHDPLLREFQEGRLLFPPTYKFDR 175
Cdd:cd09101   165 KQL-NAFDISLrfthLFWFGDLNYRL-DMDIQEILNYITRKEFDPLLAVDQLNLEREKNKVFLRFREEEISFPPTYRYER 242

                         170       180       190       200       210       220       230
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 1370471300 176 NSNDYDTSEKKRK-------PAWTDRILWRLKrqpcagpdtpipPASHFSLSLRGYSSHMTygISDHKPVSGTFDL 244
Cdd:cd09101   243 GSRDTYMWQKQKTtgmrtnvPSWCDRILWKSY------------PETHIVCNSYGCTDDIV--TSDHSPVFGTFEV 304
PLN03191 PLN03191
Type I inositol-1,4,5-trisphosphate 5-phosphatase 2; Provisional
 8-247 7.71e-25

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


Pssm-ID: 215624 [Multi-domain]  Cd Length: 621  Bit Score: 106.14  E-value: 7.71e-25
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370471300   8 SFIKVSHVRMQGILLLVFAKYQHLPYIQILSTKSTPTGLFGYWGNKGGVNICLKLYGYYVSIINCHLPP-HISNNYQRLE 86
Cdd:PLN03191  363 KYVRIVSKQMVGIYVSVWVRKRLRRHINNLKVSPVGVGLMGYMGNKGSVSISMSLFQSRLCFVCSHLTSgHKDGAEQRRN 442

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370471300  87 ----------HFDRILEMQncEGRDIPNildHDLIIWFGDMNFRIEDFGLHfVRESIKNRCYGGLWEKDQLSIAKKHDPL 156
Cdd:PLN03191  443 advyeiirrtRFSSVLDTD--QPQTIPS---HDQIFWFGDLNYRLNMLDTE-VRKLVAQKRWDELINSDQLIKELRSGHV 516

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370471300 157 LREFQEGRLLFPPTYKFDRNSNDY-----DTSEKKRKPAWTDRILWRLK--RQPCagpdtpippasHFSLSLRgysshmt 229
Cdd:PLN03191  517 FDGWKEGPIKFPPTYKYEINSDRYvgenpKEGEKKRSPAWCDRILWLGKgiKQLC-----------YKRSEIR------- 578

                         250
                  ....*....|....*...
gi 1370471300 230 ygISDHKPVSGTFDLELK 247
Cdd:PLN03191  579 --LSDHRPVSSMFLVEVE 594
INPP5c_SHIP cd09091
Catalytic inositol polyphosphate 5-phosphatase (INPP5c) domain of SH2 domain containing ...
 4-243 1.01e-24

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: 102.33  E-value: 1.01e-24
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370471300   4 LSPLSFIKVSHVRMQGILLLVFAKYQHLPYIQILSTKSTPTGLFGYWGNKGGVNICLKLYGYYVSIINCHLPPHISNNYQ 83
Cdd:cd09091    69 LTSLDYKPIAMQTLWNIRIVVLAKPEHENRISHVCTSSVKTGIANTLGNKGAVGVSFMFNGTSFGFVNSHLTSGSEKKLR 148

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370471300  84 RLEHFDRILEMQNCEGR-----DIPNILDHdlIIWFGDMNFRIE--DFGLHFVRESIKNRCYGGLWEKDQLSIAKKHDPL 156
Cdd:cd09091   149 RNQNYLNILRFLSLGDKklsafNITHRFTH--LFWLGDLNYRLDlpIQEAENIIQKIEQQQFEPLLRHDQLNLEREEHKV 226

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370471300 157 LREFQEGRLLFPPTYKFDRNSNDYDTSEKKRK-------PAWTDRILWRLKrqpcagpdtpipPASHFSLSLRGYSSHMT 229
Cdd:cd09091   227 FLRFSEEEITFPPTYRYERGSRDTYAYTKQKAtgvkynlPSWCDRILWKSY------------PETHIICQSYGCTDDIV 294

                         250
                  ....*....|....
gi 1370471300 230 ygISDHKPVSGTFD 243
Cdd:cd09091   295 --TSDHSPVFGTFE 306
INPP5c_SHIP1-INPP5D cd09100
Catalytic inositol polyphosphate 5-phosphatase (INPP5c) domain of SH2 domain containing ...
 4-244 1.11e-23

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: 99.67  E-value: 1.11e-23
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370471300   4 LSPLSFIKVSHVRMQGILLLVFAKYQHLPYIQILSTKSTPTGLFGYWGNKGGVNICLKLYGYYVSIINCHLPPHISNNYQ 83
Cdd:cd09100    69 ITSISFKVIAIQTLWNIRIVVLAKPEHENRISHICTDSVKTGIANTLGNKGAVGVSFMFNGTSFGFVNSHLTSGSEKKLR 148

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370471300  84 RLEHFDRILEMQNCEGR-----DIPNILDHdlIIWFGDMNFRIE--DFGLHFVRESIKNRCYGGLWEKDQLSIAKKHDPL 156
Cdd:cd09100   149 RNQNYFNILRFLVLGDKklspfNITHRFTH--LFWLGDLNYRVElpNTEAENIIQKIKQQQYQELLPHDQLLIERKESKV 226

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370471300 157 LREFQEGRLLFPPTYKFDRNSNDY-------DTSEKKRKPAWTDRILWRLKrqpcagpdtpipPASHFSLSLRGYSSHMT 229
Cdd:cd09100   227 FLQFEEEEITFAPTYRFERGTRERyaytkqkATGMKYNLPSWCDRVLWKSY------------PLVHVVCQSYGCTDDIT 294

                         250
                  ....*....|....*
gi 1370471300 230 ygISDHKPVSGTFDL 244
Cdd:cd09100   295 --TSDHSPVFATFEV 307
INPP5A cd09092
Type I inositol polyphosphate 5-phosphatase I; Type I inositol polyphosphate 5-phosphatase I ...
 50-244 6.20e-04

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


Pssm-ID: 197326  Cd Length: 383  Bit Score: 41.30  E-value: 6.20e-04
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370471300  50 WGNKGGVNICLKLYGYYVSIINCHL-------------PPHISNNYQR-LEH-FDRILEMQNCEgrdIPNILdhdliiwF 114
Cdd:cd09092   152 WSRKGFMRTRWKINNCVFDLVNIHLfhdasnlaacessPSVYSQNRHRaLGYvLERLTDERFEK---VPFFV-------F 221

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370471300 115 GDMNFRIEDFGL----------HFVRESIKNRCYGGLWEKDQ------LSIAKK-----HDPLLREFQEGRLL------- 166
Cdd:cd09092   222 GDFNFRLDTKSVvetlcakatmQTVRKADSNIVVKLEFREKDndnkvvLQIEKKkfdyfNQDVFRDNNGKALLkfdkele 301

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370471300 167 ------------FPPTYKFDRNSNDYDTSEKKRKPAWTDRILwrlkrqpcagpdtpIPPASHFSLSLRGYSShMTYG--- 231
Cdd:cd09092   302 vfkdvlyeldisFPPSYPYSEDPEQGTQYMNTRCPAWCDRIL--------------MSHSARELKSENEEKS-VTYDmig 366

                         250
                  ....*....|....*..
gi 1370471300 232 ----ISDHKPVSGTFDL 244
Cdd:cd09092   367 pnvcMGDHKPVFLTFRI 383
 
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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