I5P1_HUMAN
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 03-AUG-2022, entry version 170.
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; 31.
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; Q14642; -.
DR PeptideAtlas; Q14642; -.
DR PRIDE; Q14642; -.
DR ProteomicsDB; 60080; -.
DR Antibodypedia; 1413; 166 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 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; 1097975at2759; -.
DR PhylomeDB; Q14642; -.
DR TreeFam; TF314246; -.
DR BioCyc; MetaCyc:HS00936-MON; -.
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 1076 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 210 other tissues.
DR ExpressionAtlas; Q14642; baseline and differential.
DR Genevisible; Q14642; HS.
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:0046855; P:inositol phosphate dephosphorylation; IDA:MGI.
DR GO; GO:0043647; P:inositol phosphate metabolic process; TAS:Reactome.
DR GO; GO:0048016; P:inositol phosphate-mediated signaling; IBA:GO_Central.
DR GO; GO:1901215; P:negative regulation of neuron death; ISS:UniProtKB.
DR GO; GO:0046856; P:phosphatidylinositol dephosphorylation; IEA:InterPro.
DR Gene3D; 3.60.10.10; -; 1.
DR InterPro; IPR036691; Endo/exonu/phosph_ase_sf.
DR InterPro; IPR005135; Endo/exonuclease/phosphatase.
DR InterPro; IPR039737; INPP5A.
DR InterPro; IPR000300; IPPc.
DR PANTHER; PTHR12997; PTHR12997; 1.
DR Pfam; PF03372; Exo_endo_phos; 1.
DR SMART; SM00128; IPPc; 1.
DR SUPFAM; SSF56219; SSF56219; 1.
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
