I5P1_MOUSE
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 03-AUG-2022, entry version 134.
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 PhosphoSitePlus; Q7TNC9; -.
DR SwissPalm; Q7TNC9; -.
DR jPOST; Q7TNC9; -.
DR MaxQB; Q7TNC9; -.
DR PeptideAtlas; Q7TNC9; -.
DR PRIDE; Q7TNC9; -.
DR ProteomicsDB; 324816; -.
DR ProteomicsDB; 334457; -. [Q7TNC9-1]
DR Antibodypedia; 1413; 166 antibodies from 25 providers.
DR DNASU; 212111; -.
DR Ensembl; ENSMUST00000026550; ENSMUSP00000026550; ENSMUSG00000025477. [Q7TNC9-2]
DR Ensembl; ENSMUST00000106098; ENSMUSP00000101704; ENSMUSG00000025477. [Q7TNC9-1]
DR GeneID; 212111; -.
DR KEGG; mmu:212111; -.
DR UCSC; uc009kfr.2; mouse. [Q7TNC9-1]
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 OMA; GDHKPVM; -.
DR OrthoDB; 642737at2759; -.
DR TreeFam; TF314246; -.
DR Reactome; R-MMU-1855183; Synthesis of IP2, IP, and Ins in the cytosol.
DR BioGRID-ORCS; 212111; 7 hits in 75 CRISPR screens.
DR ChiTaRS; Inpp5a; mouse.
DR Proteomes; UP000000589; Chromosome 7.
DR Bgee; ENSMUSG00000025477; Expressed in ileal epithelium and 262 other 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:0046855; P:inositol phosphate dephosphorylation; ISO:MGI.
DR GO; GO:1901215; P:negative regulation of neuron death; IMP: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 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
