INP4A_MOUSE
ID INP4A_MOUSE Reviewed; 939 AA.
AC Q9EPW0; Q8CBJ8;
DT 30-AUG-2005, integrated into UniProtKB/Swiss-Prot.
DT 01-MAR-2001, sequence version 1.
DT 03-AUG-2022, entry version 134.
DE RecName: Full=Inositol polyphosphate-4-phosphatase type I A;
DE AltName: Full=Inositol polyphosphate 4-phosphatase type I;
DE AltName: Full=Inositol polyphosphate 4-phosphatase-1 {ECO:0000303|PubMed:19325558};
DE Short=4-Ptase-1 {ECO:0000303|PubMed:19325558};
DE AltName: Full=Type I inositol 3,4-bisphosphate 4-phosphatase;
DE EC=3.1.3.66 {ECO:0000269|PubMed:20463662};
GN Name=Inpp4a;
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 [MRNA] (ISOFORM 1), AND FUNCTION.
RC STRAIN=C57BL/6J;
RX PubMed=11087841; DOI=10.1073/pnas.250476397;
RA Vyas P., Norris F.A., Joseph R., Majerus P.W., Orkin S.H.;
RT "Inositol polyphosphate 4-phosphatase type I regulates cell growth
RT downstream of transcription factor GATA-1.";
RL Proc. Natl. Acad. Sci. U.S.A. 97:13696-13701(2000).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2).
RC STRAIN=C57BL/6J; TISSUE=Cerebellum;
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 [3]
RP TISSUE SPECIFICITY.
RX PubMed=11485317; DOI=10.1006/bbrc.2001.5331;
RA Shearn C.T., Walker J., Norris F.A.;
RT "Identification of a novel spliceoform of inositol polyphosphate 4-
RT phosphatase type Ialpha expressed in human platelets: structure of human
RT inositol polyphosphate 4-phosphatase type I gene.";
RL Biochem. Biophys. Res. Commun. 286:119-125(2001).
RN [4]
RP CATALYTIC ACTIVITY, DISRUPTION PHENOTYPE, FUNCTION, AND SUBCELLULAR
RP LOCATION.
RX PubMed=20463662; DOI=10.1038/nature09023;
RA Sasaki J., Kofuji S., Itoh R., Momiyama T., Takayama K., Murakami H.,
RA Chida S., Tsuya Y., Takasuga S., Eguchi S., Asanuma K., Horie Y., Miura K.,
RA Davies E.M., Mitchell C., Yamazaki M., Hirai H., Takenawa T., Suzuki A.,
RA Sasaki T.;
RT "The PtdIns(3,4)P(2) phosphatase INPP4A is a suppressor of excitotoxic
RT neuronal death.";
RL Nature 465:497-501(2010).
RN [5]
RP FUNCTION.
RX PubMed=19325558; DOI=10.1038/embor.2009.28;
RA Ivetac I., Gurung R., Hakim S., Horan K.A., Sheffield D.A., Binge L.C.,
RA Majerus P.W., Tiganis T., Mitchell C.A.;
RT "Regulation of PI(3)K/Akt signalling and cellular transformation by
RT inositol polyphosphate 4-phosphatase-1.";
RL EMBO Rep. 10:487-493(2009).
RN [6]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-488, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Brain, and Testis;
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 [7]
RP INTERACTION WITH INPP5F.
RX PubMed=25869668; DOI=10.1083/jcb.201409064;
RA Nakatsu F., Messa M., Nandez R., Czapla H., Zou Y., Strittmatter S.M.,
RA De Camilli P.;
RT "Sac2/INPP5F is an inositol 4-phosphatase that functions in the endocytic
RT pathway.";
RL J. Cell Biol. 209:85-95(2015).
CC -!- FUNCTION: Catalyzes the hydrolysis of the 4-position phosphate of
CC phosphatidylinositol 3,4-bisphosphate (PubMed:20463662). Catalyzes also
CC inositol 1,3,4-trisphosphate and inositol 1,4-bisphosphate (By
CC similarity). Antagonizes the PI3K-AKT/PKB signaling pathway by
CC dephosphorylating phosphoinositides and thereby modulating cell cycle
CC progression and cell survival (PubMed:11087841, PubMed:19325558). May
CC protect neurons from excitotoxic cell death by regulating the synaptic
CC localization of cell surface N-methyl-D-aspartate-type glutamate
CC receptors (NMDARs) and NMDAR-mediated excitatory postsynaptic current
CC (PubMed:20463662). {ECO:0000250|UniProtKB:Q62784,
CC ECO:0000269|PubMed:11087841, ECO:0000269|PubMed:19325558,
CC ECO:0000269|PubMed:20463662}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=a 1,2-diacyl-sn-glycero-3-phospho-(1D-myo-inositol-3,4-
CC bisphosphate) + H2O = a 1,2-diacyl-sn-glycero-3-phospho-(1D-myo-
CC inositol-3-phosphate) + phosphate; Xref=Rhea:RHEA:17193,
CC ChEBI:CHEBI:15377, ChEBI:CHEBI:43474, ChEBI:CHEBI:57658,
CC ChEBI:CHEBI:58088; EC=3.1.3.66;
CC Evidence={ECO:0000269|PubMed:20463662};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=1D-myo-inositol 3,4-bisphosphate + H2O = 1D-myo-inositol 3-
CC phosphate + phosphate; Xref=Rhea:RHEA:43388, ChEBI:CHEBI:15377,
CC ChEBI:CHEBI:43474, ChEBI:CHEBI:58401, ChEBI:CHEBI:83241;
CC Evidence={ECO:0000250|UniProtKB:Q62784};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:43389;
CC Evidence={ECO:0000250|UniProtKB:Q62784};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=1D-myo-inositol 1,3,4-trisphosphate + H2O = 1D-myo-inositol
CC 1,3-bisphosphate + phosphate; Xref=Rhea:RHEA:43392,
CC ChEBI:CHEBI:15377, ChEBI:CHEBI:43474, ChEBI:CHEBI:58414,
CC ChEBI:CHEBI:83242; Evidence={ECO:0000250|UniProtKB:Q62784};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:43393;
CC Evidence={ECO:0000250|UniProtKB:Q62784};
CC -!- PATHWAY: Signal transduction; phosphatidylinositol signaling pathway.
CC -!- SUBUNIT: Interacts with INPP5F. {ECO:0000269|PubMed:25869668}.
CC -!- SUBCELLULAR LOCATION: Early endosome membrane
CC {ECO:0000250|UniProtKB:Q96PE3}. Recycling endosome membrane
CC {ECO:0000250|UniProtKB:Q96PE3}. Cell membrane
CC {ECO:0000250|UniProtKB:Q96PE3}. Nucleus {ECO:0000250|UniProtKB:Q96PE3}.
CC Cytoplasm {ECO:0000250|UniProtKB:Q96PE3}. Postsynaptic density
CC {ECO:0000269|PubMed:20463662}. Note=Translocates to the plasma membrane
CC upon EGF stimulation (By similarity). Shuttles between the cytoplasm
CC and the nucleus, depending on the cell cycle stage, with highest
CC amounts detected in the nucleus during the G0/G1phase (By similarity).
CC {ECO:0000250|UniProtKB:Q96PE3}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=Q9EPW0-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q9EPW0-2; Sequence=VSP_015243, VSP_015244, VSP_015245,
CC VSP_015246;
CC -!- TISSUE SPECIFICITY: Spleen, skeletal muscle, lung and uterus.
CC {ECO:0000269|PubMed:11485317}.
CC -!- DISRUPTION PHENOTYPE: Deficient mice are born at the expected Mendelian
CC ratio and are indistinguishable from wild-type at birth. However, at
CC about 14 days after birth, the growth rate of the mice slow
CC significantly and all mutants died by the fourth week. At about 12 days
CC after birth mice are unable to walk. In addition mice show extensive
CC neurodegeneration accompanied by involuntary movements atarting at
CC about 14 days after birth. {ECO:0000269|PubMed:20463662}.
CC -!- SIMILARITY: Belongs to the inositol 3,4-bisphosphate 4-phosphatase
CC family. {ECO:0000305}.
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DR EMBL; AF317838; AAG40778.1; -; mRNA.
DR EMBL; AK035867; BAC29220.1; -; mRNA.
DR CCDS; CCDS35539.1; -. [Q9EPW0-1]
DR CCDS; CCDS78570.1; -. [Q9EPW0-2]
DR RefSeq; NP_001277726.1; NM_001290797.1.
DR RefSeq; NP_001277727.1; NM_001290798.1.
DR RefSeq; NP_001277728.1; NM_001290799.1.
DR RefSeq; NP_084542.2; NM_030266.4.
DR RefSeq; NP_766559.2; NM_172971.3.
DR AlphaFoldDB; Q9EPW0; -.
DR SMR; Q9EPW0; -.
DR BioGRID; 234616; 1.
DR IntAct; Q9EPW0; 1.
DR MINT; Q9EPW0; -.
DR STRING; 10090.ENSMUSP00000110583; -.
DR SwissLipids; SLP:000000901; -.
DR iPTMnet; Q9EPW0; -.
DR PhosphoSitePlus; Q9EPW0; -.
DR SwissPalm; Q9EPW0; -.
DR MaxQB; Q9EPW0; -.
DR PaxDb; Q9EPW0; -.
DR PeptideAtlas; Q9EPW0; -.
DR PRIDE; Q9EPW0; -.
DR ProteomicsDB; 269225; -. [Q9EPW0-1]
DR ProteomicsDB; 269226; -. [Q9EPW0-2]
DR DNASU; 269180; -.
DR GeneID; 269180; -.
DR KEGG; mmu:269180; -.
DR CTD; 3631; -.
DR MGI; MGI:1931123; Inpp4a.
DR eggNOG; KOG4428; Eukaryota.
DR InParanoid; Q9EPW0; -.
DR BRENDA; 3.1.3.66; 3474.
DR Reactome; R-MMU-1660499; Synthesis of PIPs at the plasma membrane.
DR Reactome; R-MMU-1660516; Synthesis of PIPs at the early endosome membrane.
DR Reactome; R-MMU-1855183; Synthesis of IP2, IP, and Ins in the cytosol.
DR UniPathway; UPA00944; -.
DR BioGRID-ORCS; 269180; 0 hits in 74 CRISPR screens.
DR ChiTaRS; Inpp4a; mouse.
DR PRO; PR:Q9EPW0; -.
DR Proteomes; UP000000589; Unplaced.
DR RNAct; Q9EPW0; protein.
DR GO; GO:0070161; C:anchoring junction; IEA:UniProtKB-KW.
DR GO; GO:0005737; C:cytoplasm; ISS:UniProtKB.
DR GO; GO:0031901; C:early endosome membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0031965; C:nuclear membrane; ISO:MGI.
DR GO; GO:0005654; C:nucleoplasm; ISO:MGI.
DR GO; GO:0005634; C:nucleus; ISS:UniProtKB.
DR GO; GO:0005886; C:plasma membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0014069; C:postsynaptic density; IDA:UniProtKB.
DR GO; GO:0055038; C:recycling endosome membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0017161; F:inositol-1,3,4-trisphosphate 4-phosphatase activity; IEA:RHEA.
DR GO; GO:0052828; F:inositol-3,4-bisphosphate 4-phosphatase activity; IEA:RHEA.
DR GO; GO:0016316; F:phosphatidylinositol-3,4-bisphosphate 4-phosphatase activity; IBA:GO_Central.
DR GO; GO:0034597; F:phosphatidylinositol-4,5-bisphosphate 4-phosphatase activity; IEA:UniProtKB-EC.
DR GO; GO:0006798; P:polyphosphate catabolic process; TAS:MGI.
DR Gene3D; 2.60.40.150; -; 1.
DR InterPro; IPR000008; C2_dom.
DR InterPro; IPR035892; C2_domain_sf.
DR InterPro; IPR039034; INPP4.
DR PANTHER; PTHR12187; PTHR12187; 2.
DR SUPFAM; SSF49562; SSF49562; 1.
DR PROSITE; PS50004; C2; 1.
PE 1: Evidence at protein level;
KW Alternative splicing; Cell membrane; Cytoplasm; Endosome; Hydrolase;
KW Lipid metabolism; Membrane; Nucleus; Phosphoprotein; Reference proteome;
KW Synapse.
FT CHAIN 1..939
FT /note="Inositol polyphosphate-4-phosphatase type I A"
FT /id="PRO_0000190233"
FT DOMAIN 26..153
FT /note="C2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00041"
FT REGION 563..587
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT ACT_SITE 857
FT /note="Phosphocysteine intermediate"
FT /evidence="ECO:0000250|UniProtKB:Q96PE3"
FT MOD_RES 355
FT /note="Phosphotyrosine"
FT /evidence="ECO:0000250|UniProtKB:Q96PE3"
FT MOD_RES 488
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:21183079"
FT VAR_SEQ 1..265
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:16141072"
FT /id="VSP_015243"
FT VAR_SEQ 266..272
FT /note="LLEEDAA -> MCVCFAC (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:16141072"
FT /id="VSP_015244"
FT VAR_SEQ 575..585
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:16141072"
FT /id="VSP_015245"
FT VAR_SEQ 897..939
FT /note="EGCRRENTMKNVGSRKYAFNSLQLKAFPKHYRPPEGTYGKVET -> IGTRE
FT VVTQKNLSGLVPIRDLRLDPSLLCSIPLLALSPNLLIVWLFLSIAYLVTKLRCK (in
FT isoform 2)"
FT /evidence="ECO:0000303|PubMed:16141072"
FT /id="VSP_015246"
FT CONFLICT 529
FT /note="Q -> E (in Ref. 2; BAC29220)"
FT /evidence="ECO:0000305"
FT CONFLICT 553
FT /note="D -> E (in Ref. 2; BAC29220)"
FT /evidence="ECO:0000305"
FT CONFLICT 717
FT /note="S -> N (in Ref. 2; BAC29220)"
FT /evidence="ECO:0000305"
FT CONFLICT 741
FT /note="V -> F (in Ref. 2; BAC29220)"
FT /evidence="ECO:0000305"
FT CONFLICT 744
FT /note="F -> L (in Ref. 2; BAC29220)"
FT /evidence="ECO:0000305"
FT CONFLICT 783
FT /note="G -> V (in Ref. 2; BAC29220)"
FT /evidence="ECO:0000305"
FT CONFLICT 786
FT /note="G -> V (in Ref. 2; BAC29220)"
FT /evidence="ECO:0000305"
FT CONFLICT 792
FT /note="V -> L (in Ref. 2; BAC29220)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 939 AA; 105540 MW; FBF3750836FA8962 CRC64;
MTAREHSPRH GARARAMQRA STIDVAADMV GLSLAGNIQD PDEPILEFSL ACSELHTPSL
DRKPNSFVAV SVTTPPQAFW TKHAQTEIIE GTNNPIFLSS IAFFQDSLIN QMTQIKLSVY
DVKDRSQGTM YLLGSGTFVV KDLLQDRHHR LHLTLRSAES DRVGNITVIG WQMEEKSDQQ
PPVTRFLDTV NGRMVLPVDE SLTEALGIRS KYAFLRKDSL LKAVFGGAIC RMYRFPTTDG
NHLRILEQMA ESVLSLHVPR QFVKLLLEED AARVCELEEL GELSPCWESL RRQIVTQYQT
IILTYQENLT DLHQYKGPSF KASSLKADKK LEFVPTNLHI QRMRVQDDGG SDQNYDVVTI
GAPAAHCQGF KSGGLRKKLH KFEEAKKHSF EECCTSSSGQ SIIYIPQDIT RAKEIIAQIN
TLKTQVSYYA ERLSRAAKDR SATGLERTLA ILADKTRQLV TVCDCKLLAN SIHGLNAARP
DYIASKASPT STEEEQVMLR NDQDTLMARW AGRSSRSSLQ VDWHEEEWQK VWLNVDKSLE
CIIQRVDKLL QKDRLHGEGC EDAFPCSSTC SSKKDCSPPP EESSPGEWSE ALYPLLTTLT
DCVAMMSDKA KAAMVFLLMQ DSAPTIASYL SLQYRRDVVF CQTLTALICG FIIKLRNCLH
DGGFLRQLYT IGLLAQFESL LSTYGEELAM LEDMSLGIMD LRNVTFKVTQ ATSNASSDML
PVITGNRDGF NVRIPLPGPL VDSFPREIQS GMLLRVQPVL FNVGINEQQT LAERFGDTSL
QEGINGESLV RVNSYFEQFK EVLPEDCLPR SRSQTCLPEL LRFLGQNVHA RKNKNVDILW
QAAEVCRRLN GVRFTSCKSA KDRTAMSVTL EQCLILQHEH GMAPQVFTQA LECMRSEGCR
RENTMKNVGS RKYAFNSLQL KAFPKHYRPP EGTYGKVET
