INP4A_RAT
ID INP4A_RAT Reviewed; 939 AA.
AC Q62784;
DT 30-AUG-2005, integrated into UniProtKB/Swiss-Prot.
DT 01-NOV-1996, sequence version 1.
DT 03-AUG-2022, entry version 118.
DE RecName: Full=Inositol polyphosphate-4-phosphatase type I A;
DE AltName: Full=Inositol polyphosphate 4-phosphatase type I;
DE AltName: Full=Type I inositol 3,4-bisphosphate 4-phosphatase;
DE EC=3.1.3.66 {ECO:0000269|PubMed:7608176};
GN Name=Inpp4a;
OS Rattus norvegicus (Rat).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Rattus.
OX NCBI_TaxID=10116;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 1 AND 2), PROTEIN SEQUENCE OF 22-48;
RP 245-248; 330-342; 494-504; 747-752; 755-781; 795-804 AND 927-939, TISSUE
RP SPECIFICITY, CATALYTIC ACTIVITY, AND FUNCTION.
RC TISSUE=Brain;
RX PubMed=7608176; DOI=10.1074/jbc.270.27.16128;
RA Norris F.A., Auethavekiat V., Majerus P.W.;
RT "The isolation and characterization of cDNA encoding human and rat brain
RT inositol polyphosphate 4-phosphatase.";
RL J. Biol. Chem. 270:16128-16133(1995).
RN [2]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-488, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=22673903; DOI=10.1038/ncomms1871;
RA Lundby A., Secher A., Lage K., Nordsborg N.B., Dmytriyev A., Lundby C.,
RA Olsen J.V.;
RT "Quantitative maps of protein phosphorylation sites across 14 different rat
RT organs and tissues.";
RL Nat. Commun. 3:876-876(2012).
CC -!- FUNCTION: Catalyzes the hydrolysis of the 4-position phosphate of
CC phosphatidylinositol 3,4-bisphosphate (PubMed:7608176). Catalyzes also
CC inositol 1,3,4-trisphosphate and inositol 1,4-bisphosphate
CC (PubMed:7608176). Antagonizes the PI3K-AKT/PKB signaling pathway by
CC dephosphorylating phosphoinositides and thereby modulating cell cycle
CC progression and cell survival (By similarity). May protect neurons from
CC excitotoxic cell death by regulating the synaptic localization of cell
CC surface N-methyl-D-aspartate-type glutamate receptors (NMDARs) and
CC NMDAR-mediated excitatory postsynaptic current (By similarity).
CC {ECO:0000250|UniProtKB:Q9EPW0, ECO:0000269|PubMed:7608176}.
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:7608176};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:17194;
CC Evidence={ECO:0000305|PubMed:7608176};
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:0000269|PubMed:7608176};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:43389;
CC Evidence={ECO:0000305|PubMed:7608176};
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:0000269|PubMed:7608176};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:43393;
CC Evidence={ECO:0000305|PubMed:7608176};
CC -!- PATHWAY: Signal transduction; phosphatidylinositol signaling pathway.
CC {ECO:0000269|PubMed:7608176}.
CC -!- SUBUNIT: Interacts with INPP5F. {ECO:0000250|UniProtKB:Q96PE3}.
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:0000250|UniProtKB:Q9EPW0}. Note=Translocates to the plasma
CC membrane upon EGF stimulation (By similarity). Shuttles between the
CC cytoplasm and the nucleus, depending on the cell cycle stage, with
CC highest amounts detected in the nucleus during the G0/G1phase (By
CC similarity). {ECO:0000250|UniProtKB:Q96PE3}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1; Synonyms=Alpha1;
CC IsoId=Q62784-1; Sequence=Displayed;
CC Name=2; Synonyms=Alpha2;
CC IsoId=Q62784-2; Sequence=VSP_015247;
CC -!- TISSUE SPECIFICITY: Widely expressed. Expressed at highest levels in
CC the brain, heart and skeletal muscle. {ECO:0000269|PubMed:7608176}.
CC -!- SIMILARITY: Belongs to the inositol 3,4-bisphosphate 4-phosphatase
CC family. {ECO:0000305}.
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DR EMBL; U26397; AAB01069.1; -; mRNA.
DR PIR; A57487; A57487.
DR RefSeq; NP_112264.3; NM_031002.3. [Q62784-1]
DR AlphaFoldDB; Q62784; -.
DR SMR; Q62784; -.
DR BioGRID; 249487; 1.
DR STRING; 10116.ENSRNOP00000024330; -.
DR SwissLipids; SLP:000000897; -.
DR iPTMnet; Q62784; -.
DR PhosphoSitePlus; Q62784; -.
DR jPOST; Q62784; -.
DR PaxDb; Q62784; -.
DR PRIDE; Q62784; -.
DR GeneID; 80849; -.
DR KEGG; rno:80849; -.
DR UCSC; RGD:68386; rat. [Q62784-1]
DR CTD; 3631; -.
DR RGD; 68386; Inpp4a.
DR eggNOG; KOG4428; Eukaryota.
DR InParanoid; Q62784; -.
DR OrthoDB; 129165at2759; -.
DR PhylomeDB; Q62784; -.
DR BRENDA; 3.1.3.66; 5301.
DR Reactome; R-RNO-1660499; Synthesis of PIPs at the plasma membrane.
DR Reactome; R-RNO-1660516; Synthesis of PIPs at the early endosome membrane.
DR Reactome; R-RNO-1855183; Synthesis of IP2, IP, and Ins in the cytosol.
DR UniPathway; UPA00944; -.
DR PRO; PR:Q62784; -.
DR Proteomes; UP000002494; Unplaced.
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:0005634; C:nucleus; ISS:UniProtKB.
DR GO; GO:0005886; C:plasma membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0014069; C:postsynaptic density; ISS: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 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; Direct protein sequencing;
KW Endosome; Hydrolase; Lipid metabolism; Membrane; Nucleus; Phosphoprotein;
KW Reference proteome; Synapse.
FT CHAIN 1..939
FT /note="Inositol polyphosphate-4-phosphatase type I A"
FT /id="PRO_0000190234"
FT DOMAIN 26..153
FT /note="C2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00041"
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:22673903"
FT VAR_SEQ 575..585
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:7608176"
FT /id="VSP_015247"
SQ SEQUENCE 939 AA; 105589 MW; 1DC4B3F0A8F47D0D CRC64;
MTAREHSPRH GARARAMQRA STIDVTADMV GLSLAGNIQD PDEPILEFSL ACSELHTPSL
DRKPNSFVAV SVTTPPQAFW TKHAQTEIIE GTNNPIFLSS IAFFQDSLIN QMTQIKLSVY
DVKDRSQGTM YLLGSGTFVV KDLLQDRHHR LHLTLRSAES DRVGNITVIG WQMEEKSDQQ
PPVTRSLDTV NGRMVLPVDE SLTEALGIRS KYASLRKDSL LKAVFGGAIC RMYRFPTTDG
NHLRILEQMA ESVLSLHVPR QFVKLLLEED AARVCELEEL GELSPCWESL RRQIVTQYQT
IILTYQENLT DLHQYKGPSF KASSLKADKK LEFVPTNLHI QRMRVQDDGG SDQNYDVVTI
GAPAAHCQGF KSGGLRKKLH KFEEAKKHSF EECCTSSTCQ SIIYIPQDVV RAKEIIAQIN
TLKTQVSYYA ERLSRAAKDR SATGLERTLA ILADKTRQLV TVCDCKLLAN SIHGLNAARP
DYIASKASPT STEEEQVMLR NDQDTLMARW AGRSSRSSLQ VDWHEEEWEK VWLNVDKSLE
CIIQRVDKLL QKERLHGEGG EDVFPCSSTC SSKKDCSPPP EESCPGEWSE ALYPLLTTLT
DCVAMMSDKA KAAMVFLLMQ TAAPTIASYL SLQYRRDVVF CQTLTALICG FIIKLRNCLH
DGGFLRQLYT IGLLAQFESL LSTYGEELAM LEDMSLGIMD LRNVTFKVTQ ATSNASSDML
PVITGNRDGF NVRIPLPGPL FDSLPREIQS GMLLRVQPVL FNVGINEQQT LAERFGDTSL
QEVINVESLV RLNSYFEQFK EVLPEDCLPR SRSQTCLPEL LRFLGQNVHA RKNKNVDILW
QAAEVCRRLN GVRFTSCKSA KDRTAMSVTL EQCLILQHEH GMAPQVFTQA LECMRSEGCR
RENTMKNVGS RKYAFNSLQL KAFPKHYRPP EGTYGKVET
