ID   I5P1_MOUSE              Reviewed;         412 AA.
AC   Q7TNC9; E9QAS7; Q8BNK3;
DT   07-OCT-2020, integrated into UniProtKB/Swiss-Prot.
DT   01-OCT-2003, sequence version 1.
DT   24-JAN-2024, entry version 141.
DE   RecName: Full=Inositol polyphosphate-5-phosphatase A;
DE            EC=3.1.3.56 {ECO:0000269|PubMed:26051944};
DE   AltName: Full=Type I inositol 1,4,5-trisphosphate 5-phosphatase;
DE            Short=5PTase;
DE   Flags: Precursor;
GN   Name=Inpp5a;
OS   Mus musculus (Mouse).
OC   Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC   Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC   Murinae; Mus; Mus.
OX   NCBI_TaxID=10090;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 2).
RC   STRAIN=C57BL/6J, and NOD; TISSUE=Spleen;
RX   PubMed=16141072; DOI=10.1126/science.1112014;
RA   Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N.,
RA   Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K.,
RA   Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J.,
RA   Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R.,
RA   Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T.,
RA   Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A.,
RA   Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B.,
RA   Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M.,
RA   Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S.,
RA   Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E.,
RA   Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D.,
RA   Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M.,
RA   Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H.,
RA   Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V.,
RA   Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S.,
RA   Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H.,
RA   Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N.,
RA   Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F.,
RA   Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G.,
RA   Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z.,
RA   Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C.,
RA   Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y.,
RA   Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S.,
RA   Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K.,
RA   Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R.,
RA   van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H.,
RA   Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M.,
RA   Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C.,
RA   Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S.,
RA   Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K.,
RA   Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M.,
RA   Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C.,
RA   Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A.,
RA   Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y.;
RT   "The transcriptional landscape of the mammalian genome.";
RL   Science 309:1559-1563(2005).
RN   [2]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC   STRAIN=C57BL/6J;
RX   PubMed=19468303; DOI=10.1371/journal.pbio.1000112;
RA   Church D.M., Goodstadt L., Hillier L.W., Zody M.C., Goldstein S., She X.,
RA   Bult C.J., Agarwala R., Cherry J.L., DiCuccio M., Hlavina W., Kapustin Y.,
RA   Meric P., Maglott D., Birtle Z., Marques A.C., Graves T., Zhou S.,
RA   Teague B., Potamousis K., Churas C., Place M., Herschleb J., Runnheim R.,
RA   Forrest D., Amos-Landgraf J., Schwartz D.C., Cheng Z., Lindblad-Toh K.,
RA   Eichler E.E., Ponting C.P.;
RT   "Lineage-specific biology revealed by a finished genome assembly of the
RT   mouse.";
RL   PLoS Biol. 7:E1000112-E1000112(2009).
RN   [3]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC   STRAIN=C57BL/6J; TISSUE=Brain;
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   [4]
RP   IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX   PubMed=21183079; DOI=10.1016/j.cell.2010.12.001;
RA   Huttlin E.L., Jedrychowski M.P., Elias J.E., Goswami T., Rad R.,
RA   Beausoleil S.A., Villen J., Haas W., Sowa M.E., Gygi S.P.;
RT   "A tissue-specific atlas of mouse protein phosphorylation and expression.";
RL   Cell 143:1174-1189(2010).
RN   [5]
RP   FUNCTION, CATALYTIC ACTIVITY, DISRUPTION PHENOTYPE, SUBCELLULAR LOCATION,
RP   AND TISSUE SPECIFICITY.
RX   PubMed=26051944; DOI=10.1007/s10048-015-0450-4;
RA   Yang A.W., Sachs A.J., Nystuen A.M.;
RT   "Deletion of Inpp5a causes ataxia and cerebellar degeneration in mice.";
RL   Neurogenetics 16:277-285(2015).
RN   [6]
RP   INTERACTION WITH TASOR, AND TISSUE SPECIFICITY.
RX   PubMed=31112734; DOI=10.1016/j.yexcr.2019.05.018;
RA   Gresakova V., Novosadova V., Prochazkova M., Bhargava S., Jenickova I.,
RA   Prochazka J., Sedlacek R.;
RT   "Fam208a orchestrates interaction protein network essential for early
RT   embryonic development and cell division.";
RL   Exp. Cell Res. 382:111437-111437(2019).
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:26051944). Plays a crucial role in the survival of cerebellar
CC       Purkinje cells (PubMed:26051944). {ECO:0000269|PubMed:26051944}.
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:26051944};
CC       PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:19798;
CC         Evidence={ECO:0000305|PubMed:26051944};
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;
CC         Evidence={ECO:0000269|PubMed:26051944};
CC       PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:11393;
CC         Evidence={ECO:0000305|PubMed:26051944};
CC   -!- SUBUNIT: Interacts with TASOR. {ECO:0000269|PubMed:31112734}.
CC   -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000250|UniProtKB:Q14642};
CC       Lipid-anchor {ECO:0000250|UniProtKB:Q14642}. Cell projection, dendrite
CC       {ECO:0000269|PubMed:26051944}.
CC   -!- ALTERNATIVE PRODUCTS:
CC       Event=Alternative splicing; Named isoforms=2;
CC       Name=1;
CC         IsoId=Q7TNC9-1; Sequence=Displayed;
CC       Name=2;
CC         IsoId=Q7TNC9-2; Sequence=VSP_060756;
CC   -!- TISSUE SPECIFICITY: Expressed at high levels in cerebellar Purkinje
CC       cells (at protein level) (PubMed:26051944). Expressed in Sertoli cells
CC       of the testis (PubMed:31112734). {ECO:0000269|PubMed:26051944,
CC       ECO:0000269|PubMed:31112734}.
CC   -!- PTM: Isoprenylation at Cys-409 is required for localization at the
CC       membrane. {ECO:0000250|UniProtKB:Q14642}.
CC   -!- DISRUPTION PHENOTYPE: Genetic deletion causes a perinatal lethal
CC       phenotype in most mutant mice (PubMed:26051944). A small percentage of
CC       mutants thrive and have a phenotype characterized by an ataxic gait and
CC       progressive Purkinje cell degeneration (PubMed:26051944). Purkinje cell
CC       death is spatially patterned with surviving Purkinje cells appearing
CC       normal and maintaining molecular layer morphology (PubMed:26051944).
CC       Phosphatase activity toward phosphoinositol substrates is reduced in
CC       the mutant relative to wild-type littermates (PubMed:26051944).
CC       {ECO:0000269|PubMed:26051944}.
CC   -!- SIMILARITY: Belongs to the inositol 1,4,5-trisphosphate 5-phosphatase
CC       type I family. {ECO:0000305}.
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DR   EMBL; AK083449; BAC38919.1; -; mRNA.
DR   EMBL; AK171360; BAE42408.1; -; mRNA.
DR   EMBL; AK171880; BAE42716.1; -; mRNA.
DR   EMBL; AC112670; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR   EMBL; AC118735; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR   EMBL; BC056341; AAH56341.1; -; mRNA.
DR   CCDS; CCDS21954.1; -. [Q7TNC9-2]
DR   CCDS; CCDS52428.1; -. [Q7TNC9-1]
DR   RefSeq; NP_001120835.1; NM_001127363.1. [Q7TNC9-1]
DR   RefSeq; NP_898967.2; NM_183144.3. [Q7TNC9-2]
DR   AlphaFoldDB; Q7TNC9; -.
DR   STRING; 10090.ENSMUSP00000026550; -.
DR   iPTMnet; Q7TNC9; -.
DR   PhosphoSitePlus; Q7TNC9; -.
DR   SwissPalm; Q7TNC9; -.
DR   jPOST; Q7TNC9; -.
DR   MaxQB; Q7TNC9; -.
DR   PaxDb; 10090-ENSMUSP00000026550; -.
DR   PeptideAtlas; Q7TNC9; -.
DR   ProteomicsDB; 324816; -.
DR   ProteomicsDB; 334457; -. [Q7TNC9-1]
DR   Antibodypedia; 1413; 185 antibodies from 25 providers.
DR   DNASU; 212111; -.
DR   Ensembl; ENSMUST00000026550.14; ENSMUSP00000026550.8; ENSMUSG00000025477.15. [Q7TNC9-2]
DR   Ensembl; ENSMUST00000106098.8; ENSMUSP00000101704.2; ENSMUSG00000025477.15. [Q7TNC9-1]
DR   GeneID; 212111; -.
DR   KEGG; mmu:212111; -.
DR   UCSC; uc009kfr.2; mouse. [Q7TNC9-1]
DR   AGR; MGI:2686961; -.
DR   CTD; 3632; -.
DR   MGI; MGI:2686961; Inpp5a.
DR   VEuPathDB; HostDB:ENSMUSG00000025477; -.
DR   eggNOG; KOG1976; Eukaryota.
DR   GeneTree; ENSGT00390000015226; -.
DR   HOGENOM; CLU_057709_1_0_1; -.
DR   InParanoid; Q7TNC9; -.
DR   OMA; GDHKPVM; -.
DR   OrthoDB; 2898734at2759; -.
DR   TreeFam; TF314246; -.
DR   Reactome; R-MMU-1855183; Synthesis of IP2, IP, and Ins in the cytosol.
DR   BioGRID-ORCS; 212111; 7 hits in 80 CRISPR screens.
DR   ChiTaRS; Inpp5a; mouse.
DR   PRO; PR:Q7TNC9; -.
DR   Proteomes; UP000000589; Chromosome 7.
DR   Bgee; ENSMUSG00000025477; Expressed in ileal epithelium and 266 other cell types or tissues.
DR   ExpressionAtlas; Q7TNC9; baseline and differential.
DR   GO; GO:0030425; C:dendrite; IDA:UniProtKB.
DR   GO; GO:0016020; C:membrane; ISO:MGI.
DR   GO; GO:0005886; C:plasma membrane; ISS: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; IEA:UniProtKB-EC.
DR   GO; GO:0004445; F:inositol-polyphosphate 5-phosphatase activity; IMP:UniProtKB.
DR   GO; GO:0042731; F:PH domain binding; ISO:MGI.
DR   GO; GO:1900737; P:negative regulation of phospholipase C-activating G protein-coupled receptor signaling pathway; IMP: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.
PE   1: Evidence at protein level;
KW   Alternative splicing; Cell membrane; Cell projection; Hydrolase;
KW   Lipoprotein; Membrane; Prenylation; Reference proteome.
FT   CHAIN           1..409
FT                   /note="Inositol polyphosphate-5-phosphatase A"
FT                   /id="PRO_0000451144"
FT   PROPEP          410..412
FT                   /note="Removed in mature form"
FT                   /evidence="ECO:0000250|UniProtKB:Q14642"
FT                   /id="PRO_0000451145"
FT   LIPID           409
FT                   /note="S-farnesyl cysteine"
FT                   /evidence="ECO:0000250|UniProtKB:Q14642"
FT   VAR_SEQ         401..412
FT                   /note="PHAHVHKCCVVQ -> RCQRRERILERPPCSSVSNSSS (in isoform
FT                   2)"
FT                   /evidence="ECO:0000305"
FT                   /id="VSP_060756"
FT   CONFLICT        11
FT                   /note="A -> V (in Ref. 1; BAC38919)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        27
FT                   /note="E -> D (in Ref. 1; BAC38919)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        36
FT                   /note="E -> G (in Ref. 1; BAC38919)"
FT                   /evidence="ECO:0000305"
SQ   SEQUENCE   412 AA;  47622 MW;  1304F5691FA9832B CRC64;
     MAGKAAAPGT AVLLVTANVG SLFDDPENLQ KNWLREFYQV LHTHKPHFMA LHCQEFGGKN
     YEASMSHVDK FVKELLSSDA MKEYNRARVY LDENYKSQEH FTALGSFYFL HESLKNIYQF
     DFKAKKYKKV TGKEIYSDTL ESTPMLEKEK FPQDYFPECK WSRKGFIRTR WCIADCAFDL
     VNIHLFHDAS NLVAWETSPS VYSGVRHKAL GYVLDRIIDQ RFEKVSYFVF GDFNFRLDSK
     SVVETLCTKA TMQTVRAADT NEVVKLIFRE SDNDRKVVLQ LEKKLFDYFN QDVFRDNNGT
     ALLEFDKELS VFKDRLYELD ISFPPSYPYS EDSSQGEQYM NTRCPAWCDR ILMSLSAKEL
     VLKSESEEKV ATYDHIGPNV CMGDHKPVFL AFRIAPGAGK PHAHVHKCCV VQ
//