ID   I5P1_HUMAN              Reviewed;         412 AA.
AC   Q14642; D3DXI3; Q14640; Q5JSF1;
DT   15-JUL-1998, integrated into UniProtKB/Swiss-Prot.
DT   01-NOV-1996, sequence version 1.
DT   24-JAN-2024, entry version 178.
DE   RecName: Full=Inositol polyphosphate-5-phosphatase A;
DE            EC=3.1.3.56 {ECO:0000269|PubMed:8013665, ECO:0000269|PubMed:8626616, ECO:0000269|PubMed:8769125};
DE   AltName: Full=43 kDa inositol polyphosphate 5-phosphatase {ECO:0000303|PubMed:8006039};
DE   AltName: Full=Type I inositol 1,4,5-trisphosphate 5-phosphatase {ECO:0000303|PubMed:8013665};
DE            Short=5PTase {ECO:0000303|PubMed:8013665};
DE   Flags: Precursor;
GN   Name=INPP5A {ECO:0000312|HGNC:HGNC:6076};
GN   Synonyms=5PTASE {ECO:0000303|PubMed:8013665};
OS   Homo sapiens (Human).
OC   Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC   Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC   Homo.
OX   NCBI_TaxID=9606;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, TISSUE SPECIFICITY, AND CATALYTIC
RP   ACTIVITY.
RC   TISSUE=Brain;
RX   PubMed=8013665; DOI=10.1016/0014-5793(94)00509-5;
RA   de Smedt F., Verjans B., Mailleux P., Erneux C.;
RT   "Cloning and expression of human brain type I inositol 1,4,5-trisphosphate
RT   5-phosphatase. High levels of mRNA in cerebellar Purkinje cells.";
RL   FEBS Lett. 347:69-72(1994).
RN   [2]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX   PubMed=15164054; DOI=10.1038/nature02462;
RA   Deloukas P., Earthrowl M.E., Grafham D.V., Rubenfield M., French L.,
RA   Steward C.A., Sims S.K., Jones M.C., Searle S., Scott C., Howe K.,
RA   Hunt S.E., Andrews T.D., Gilbert J.G.R., Swarbreck D., Ashurst J.L.,
RA   Taylor A., Battles J., Bird C.P., Ainscough R., Almeida J.P.,
RA   Ashwell R.I.S., Ambrose K.D., Babbage A.K., Bagguley C.L., Bailey J.,
RA   Banerjee R., Bates K., Beasley H., Bray-Allen S., Brown A.J., Brown J.Y.,
RA   Burford D.C., Burrill W., Burton J., Cahill P., Camire D., Carter N.P.,
RA   Chapman J.C., Clark S.Y., Clarke G., Clee C.M., Clegg S., Corby N.,
RA   Coulson A., Dhami P., Dutta I., Dunn M., Faulkner L., Frankish A.,
RA   Frankland J.A., Garner P., Garnett J., Gribble S., Griffiths C.,
RA   Grocock R., Gustafson E., Hammond S., Harley J.L., Hart E., Heath P.D.,
RA   Ho T.P., Hopkins B., Horne J., Howden P.J., Huckle E., Hynds C.,
RA   Johnson C., Johnson D., Kana A., Kay M., Kimberley A.M., Kershaw J.K.,
RA   Kokkinaki M., Laird G.K., Lawlor S., Lee H.M., Leongamornlert D.A.,
RA   Laird G., Lloyd C., Lloyd D.M., Loveland J., Lovell J., McLaren S.,
RA   McLay K.E., McMurray A., Mashreghi-Mohammadi M., Matthews L., Milne S.,
RA   Nickerson T., Nguyen M., Overton-Larty E., Palmer S.A., Pearce A.V.,
RA   Peck A.I., Pelan S., Phillimore B., Porter K., Rice C.M., Rogosin A.,
RA   Ross M.T., Sarafidou T., Sehra H.K., Shownkeen R., Skuce C.D., Smith M.,
RA   Standring L., Sycamore N., Tester J., Thorpe A., Torcasso W., Tracey A.,
RA   Tromans A., Tsolas J., Wall M., Walsh J., Wang H., Weinstock K., West A.P.,
RA   Willey D.L., Whitehead S.L., Wilming L., Wray P.W., Young L., Chen Y.,
RA   Lovering R.C., Moschonas N.K., Siebert R., Fechtel K., Bentley D.,
RA   Durbin R.M., Hubbard T., Doucette-Stamm L., Beck S., Smith D.R., Rogers J.;
RT   "The DNA sequence and comparative analysis of human chromosome 10.";
RL   Nature 429:375-381(2004).
RN   [3]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA   Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M.,
RA   Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J.,
RA   Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S.,
RA   Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H.,
RA   Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K.,
RA   Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D.,
RA   Hunkapiller M.W., Myers E.W., Venter J.C.;
RL   Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases.
RN   [4]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RX   PubMed=15489334; DOI=10.1101/gr.2596504;
RG   The MGC Project Team;
RT   "The status, quality, and expansion of the NIH full-length cDNA project:
RT   the Mammalian Gene Collection (MGC).";
RL   Genome Res. 14:2121-2127(2004).
RN   [5]
RP   NUCLEOTIDE SEQUENCE [MRNA] OF 49-412, TISSUE SPECIFICITY, AND SUBCELLULAR
RP   LOCATION.
RC   TISSUE=Placenta;
RX   PubMed=8006039; DOI=10.1016/s0021-9258(17)32555-3;
RA   Laxminarayan K.M., Chan B.K., Tetaz T., Bird P.I., Mitchell C.A.;
RT   "Characterization of a cDNA encoding the 43-kDa membrane-associated
RT   inositol-polyphosphate 5-phosphatase.";
RL   J. Biol. Chem. 269:17305-17310(1994).
RN   [6]
RP   CATALYTIC ACTIVITY, AND FUNCTION.
RX   PubMed=8769125; DOI=10.1006/bbrc.1996.1161;
RA   Drayer A.L., Pesesse X., De Smedt F., Woscholski R., Parker P., Erneux C.;
RT   "Cloning and expression of a human placenta inositol 1,3,4,5-
RT   tetrakisphosphate and phosphatidylinositol 3,4,5-trisphosphate 5-
RT   phosphatase.";
RL   Biochem. Biophys. Res. Commun. 225:243-249(1996).
RN   [7]
RP   FUNCTION, CATALYTIC ACTIVITY, SUBCELLULAR LOCATION, ISOPRENYLATION AT
RP   CYS-409, AND MUTAGENESIS OF 408-CYS--GLN-412 AND CYS-409.
RX   PubMed=8626616; DOI=10.1074/jbc.271.17.10419;
RA   De Smedt F., Boom A., Pesesse X., Schiffmann S.N., Erneux C.;
RT   "Post-translational modification of human brain type I inositol-1,4,5-
RT   trisphosphate 5-phosphatase by farnesylation.";
RL   J. Biol. Chem. 271:10419-10424(1996).
CC   -!- FUNCTION: Phosphatase that specifically hydrolyzes the 5-phosphate of
CC       inositol 1,4,5-trisphosphate to inositol 1,4-bisphosphate, and inositol
CC       1,3,4,5-tetrasphosphate to inositol 1,3,4-trisphosphate
CC       (PubMed:8013665, PubMed:8769125, PubMed:8626616). Plays a crucial role
CC       in the survival of cerebellar Purkinje cells (By similarity).
CC       {ECO:0000250|UniProtKB:Q7TNC9, ECO:0000269|PubMed:8013665,
CC       ECO:0000269|PubMed:8626616, ECO:0000269|PubMed:8769125}.
CC   -!- CATALYTIC ACTIVITY:
CC       Reaction=1D-myo-inositol 1,4,5-trisphosphate + H2O = 1D-myo-inositol
CC         1,4-bisphosphate + phosphate; Xref=Rhea:RHEA:19797,
CC         ChEBI:CHEBI:15377, ChEBI:CHEBI:43474, ChEBI:CHEBI:58282,
CC         ChEBI:CHEBI:203600; EC=3.1.3.56;
CC         Evidence={ECO:0000269|PubMed:8013665, ECO:0000269|PubMed:8626616,
CC         ECO:0000269|PubMed:8769125};
CC       PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:19798;
CC         Evidence={ECO:0000305|PubMed:8769125};
CC   -!- CATALYTIC ACTIVITY:
CC       Reaction=1D-myo-inositol 1,3,4,5-tetrakisphosphate + H2O = 1D-myo-
CC         inositol 1,3,4-trisphosphate + phosphate; Xref=Rhea:RHEA:11392,
CC         ChEBI:CHEBI:15377, ChEBI:CHEBI:43474, ChEBI:CHEBI:57895,
CC         ChEBI:CHEBI:58414; EC=3.1.3.56; Evidence={ECO:0000269|PubMed:8626616,
CC         ECO:0000269|PubMed:8769125};
CC       PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:11393;
CC         Evidence={ECO:0000305|PubMed:8769125};
CC   -!- SUBUNIT: Interacts with TASOR. {ECO:0000250|UniProtKB:Q7TNC9}.
CC   -!- INTERACTION:
CC       Q14642; P08567: PLEK; NbExp=4; IntAct=EBI-8670520, EBI-2565501;
CC       Q14642; Q15562-2: TEAD2; NbExp=3; IntAct=EBI-8670520, EBI-9370956;
CC   -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000269|PubMed:8626616,
CC       ECO:0000305|PubMed:8006039}; Lipid-anchor {ECO:0000269|PubMed:8626616,
CC       ECO:0000305}. Cell projection, dendrite {ECO:0000250|UniProtKB:Q7TNC9}.
CC   -!- TISSUE SPECIFICITY: Predominantly expressed in heart, brain, and
CC       skeletal muscle (PubMed:8006039). In brain; high level in Purkinje
CC       cells (PubMed:8013665). {ECO:0000269|PubMed:8006039,
CC       ECO:0000269|PubMed:8013665}.
CC   -!- PTM: Isoprenylation at Cys-409 is required for localization at the
CC       membrane. {ECO:0000269|PubMed:8626616}.
CC   -!- SIMILARITY: Belongs to the inositol 1,4,5-trisphosphate 5-phosphatase
CC       type I family. {ECO:0000305}.
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DR   EMBL; X77567; CAA54676.1; -; mRNA.
DR   EMBL; AL392043; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR   EMBL; AL451069; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR   EMBL; AL356603; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR   EMBL; CH471211; EAW61306.1; -; Genomic_DNA.
DR   EMBL; CH471211; EAW61307.1; -; Genomic_DNA.
DR   EMBL; BC096280; AAH96280.1; -; mRNA.
DR   EMBL; Z31695; CAA83500.1; -; mRNA.
DR   CCDS; CCDS7669.2; -.
DR   PIR; S45721; S45721.
DR   RefSeq; NP_001307971.1; NM_001321042.1.
DR   RefSeq; NP_005530.3; NM_005539.4.
DR   AlphaFoldDB; Q14642; -.
DR   BioGRID; 109844; 35.
DR   IntAct; Q14642; 15.
DR   MINT; Q14642; -.
DR   STRING; 9606.ENSP00000357583; -.
DR   BindingDB; Q14642; -.
DR   ChEMBL; CHEMBL4243; -.
DR   GuidetoPHARMACOLOGY; 1453; -.
DR   SwissLipids; SLP:000000952; -.
DR   DEPOD; INPP5A; -.
DR   iPTMnet; Q14642; -.
DR   PhosphoSitePlus; Q14642; -.
DR   SwissPalm; Q14642; -.
DR   BioMuta; INPP5A; -.
DR   DMDM; 3122245; -.
DR   EPD; Q14642; -.
DR   jPOST; Q14642; -.
DR   MassIVE; Q14642; -.
DR   MaxQB; Q14642; -.
DR   PaxDb; 9606-ENSP00000357583; -.
DR   PeptideAtlas; Q14642; -.
DR   ProteomicsDB; 60080; -.
DR   Pumba; Q14642; -.
DR   Antibodypedia; 1413; 185 antibodies from 25 providers.
DR   DNASU; 3632; -.
DR   Ensembl; ENST00000368594.8; ENSP00000357583.3; ENSG00000068383.19.
DR   GeneID; 3632; -.
DR   KEGG; hsa:3632; -.
DR   MANE-Select; ENST00000368594.8; ENSP00000357583.3; NM_005539.5; NP_005530.3.
DR   UCSC; uc001llp.4; human.
DR   AGR; HGNC:6076; -.
DR   CTD; 3632; -.
DR   DisGeNET; 3632; -.
DR   GeneCards; INPP5A; -.
DR   HGNC; HGNC:6076; INPP5A.
DR   HPA; ENSG00000068383; Low tissue specificity.
DR   MIM; 600106; gene.
DR   neXtProt; NX_Q14642; -.
DR   OpenTargets; ENSG00000068383; -.
DR   PharmGKB; PA29884; -.
DR   VEuPathDB; HostDB:ENSG00000068383; -.
DR   eggNOG; KOG1976; Eukaryota.
DR   GeneTree; ENSGT00390000015226; -.
DR   InParanoid; Q14642; -.
DR   OMA; GDHKPVM; -.
DR   OrthoDB; 2898734at2759; -.
DR   PhylomeDB; Q14642; -.
DR   TreeFam; TF314246; -.
DR   BioCyc; MetaCyc:HS00936-MONOMER; -.
DR   BRENDA; 3.1.3.56; 2681.
DR   PathwayCommons; Q14642; -.
DR   Reactome; R-HSA-1855183; Synthesis of IP2, IP, and Ins in the cytosol.
DR   SignaLink; Q14642; -.
DR   BioGRID-ORCS; 3632; 20 hits in 1168 CRISPR screens.
DR   ChiTaRS; INPP5A; human.
DR   GeneWiki; INPP5A; -.
DR   GenomeRNAi; 3632; -.
DR   Pharos; Q14642; Tchem.
DR   PRO; PR:Q14642; -.
DR   Proteomes; UP000005640; Chromosome 10.
DR   RNAct; Q14642; Protein.
DR   Bgee; ENSG00000068383; Expressed in lateral nuclear group of thalamus and 212 other cell types or tissues.
DR   ExpressionAtlas; Q14642; baseline and differential.
DR   GO; GO:0030425; C:dendrite; ISS:UniProtKB.
DR   GO; GO:0016020; C:membrane; IDA:MGI.
DR   GO; GO:0005886; C:plasma membrane; IDA:UniProtKB.
DR   GO; GO:0052659; F:inositol-1,3,4,5-tetrakisphosphate 5-phosphatase activity; IEA:UniProtKB-EC.
DR   GO; GO:0052658; F:inositol-1,4,5-trisphosphate 5-phosphatase activity; TAS:Reactome.
DR   GO; GO:0004445; F:inositol-polyphosphate 5-phosphatase activity; IDA:UniProtKB.
DR   GO; GO:0042731; F:PH domain binding; IPI:BHF-UCL.
DR   GO; GO:0043647; P:inositol phosphate metabolic process; TAS:Reactome.
DR   GO; GO:1900737; P:negative regulation of phospholipase C-activating G protein-coupled receptor signaling pathway; ISS:UniProtKB.
DR   GO; GO:0046856; P:phosphatidylinositol dephosphorylation; IEA:InterPro.
DR   CDD; cd09092; INPP5A; 1.
DR   Gene3D; 3.60.10.10; Endonuclease/exonuclease/phosphatase; 1.
DR   InterPro; IPR036691; Endo/exonu/phosph_ase_sf.
DR   InterPro; IPR039737; INPP5A.
DR   InterPro; IPR000300; IPPc.
DR   PANTHER; PTHR12997:SF2; INOSITOL POLYPHOSPHATE-5-PHOSPHATASE A; 1.
DR   PANTHER; PTHR12997; TYPE I INOSITOL-1,4,5-TRISPHOSPHATE 5-PHOSPHATASE; 1.
DR   SMART; SM00128; IPPc; 1.
DR   SUPFAM; SSF56219; DNase I-like; 1.
DR   Genevisible; Q14642; HS.
PE   1: Evidence at protein level;
KW   Cell membrane; Cell projection; Hydrolase; Lipoprotein; Membrane;
KW   Prenylation; Reference proteome.
FT   CHAIN           1..409
FT                   /note="Inositol polyphosphate-5-phosphatase A"
FT                   /id="PRO_0000209719"
FT   PROPEP          410..412
FT                   /note="Removed in mature form"
FT                   /evidence="ECO:0000269|PubMed:8626616"
FT                   /id="PRO_0000396780"
FT   LIPID           409
FT                   /note="S-farnesyl cysteine"
FT                   /evidence="ECO:0000269|PubMed:8626616"
FT   VARIANT         45
FT                   /note="K -> R (in dbSNP:rs1133400)"
FT                   /id="VAR_034006"
FT   MUTAGEN         408..412
FT                   /note="Missing: Loss of membrane localization. No loss of
FT                   enzyme activity."
FT                   /evidence="ECO:0000269|PubMed:8626616"
FT   MUTAGEN         409
FT                   /note="C->S: Loss of prenylation and membrane localization.
FT                   No loss of enzyme activity."
FT                   /evidence="ECO:0000269|PubMed:8626616"
FT   CONFLICT        152..172
FT                   /note="PQDYFPECKWSRKGFIRTRWC -> RRLLPRVQMVKKRLHPDEVV (in
FT                   Ref. 5; CAA83500)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        247..251
FT                   /note="CTKAT -> SAKPP (in Ref. 5; CAA83500)"
FT                   /evidence="ECO:0000305"
SQ   SEQUENCE   412 AA;  47820 MW;  F55C0DFDDA01A850 CRC64;
     MAGKAAAPGT AVLLVTANVG SLFDDPENLQ KNWLREFYQV VHTHKPHFMA LHCQEFGGKN
     YEASMSHVDK FVKELLSSDA MKEYNRARVY LDENYKSQEH FTALGSFYFL HESLKNIYQF
     DFKAKKYRKV AGKEIYSDTL ESTPMLEKEK FPQDYFPECK WSRKGFIRTR WCIADCAFDL
     VNIHLFHDAS NLVAWETSPS VYSGIRHKAL GYVLDRIIDQ RFEKVSYFVF GDFNFRLDSK
     SVVETLCTKA TMQTVRAADT NEVVKLIFRE SDNDRKVMLQ LEKKLFDYFN QEVFRDNNGT
     ALLEFDKELS VFKDRLYELD ISFPPSYPYS EDARQGEQYM NTRCPAWCDR ILMSPSAKEL
     VLRSESEEKV VTYDHIGPNV CMGDHKPVFL AFRIMPGAGK PHAHVHKCCV VQ
//