ID   IMPA2_HUMAN             Reviewed;         288 AA.
AC   O14732; B0YJ29; Q9UJT3;
DT   15-DEC-1998, integrated into UniProtKB/Swiss-Prot.
DT   01-JAN-1998, sequence version 1.
DT   27-MAR-2024, entry version 193.
DE   RecName: Full=Inositol monophosphatase 2;
DE            Short=IMP 2;
DE            Short=IMPase 2;
DE            EC=3.1.3.25 {ECO:0000269|PubMed:17068342};
DE   AltName: Full=Inositol-1(or 4)-monophosphatase 2;
DE   AltName: Full=Myo-inositol monophosphatase A2;
GN   Name=IMPA2; Synonyms=IMP.18P;
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] (ISOFORM 1).
RX   PubMed=9322233; DOI=10.1038/sj.mp.4000325;
RA   Yoshikawa T., Turner G., Esterling L.E., Sanders A.R.,
RA   Detera-Wadleigh S.D.;
RT   "A novel human myo-inositol monophosphatase gene, IMP.18p, maps to a
RT   susceptibility region for bipolar disorder.";
RL   Mol. Psychiatry 2:393-397(1997).
RN   [2]
RP   NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RX   PubMed=10822345; DOI=10.1038/sj.mp.4000681;
RA   Sjoeholt G., Gulbrandsen A.K., Lovlie R., Berle J., Molven A., Steen V.M.;
RT   "A human myo-inositol monophosphatase gene (IMPA2) localized in a putative
RT   susceptibility region for bipolar disorder on chromosome 18p11.2: genomic
RT   structure and polymorphism screening in manic-depressive patients.";
RL   Mol. Psychiatry 5:172-180(2000).
RN   [3]
RP   NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2).
RA   Parthasarathy L., Parthasarathy R.;
RT   "Molecular characterization of a novel form of human brain inositol
RT   monophosphatase A2b.";
RL   Submitted (OCT-1999) to the EMBL/GenBank/DDBJ databases.
RN   [4]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RA   Kalnine N., Chen X., Rolfs A., Halleck A., Hines L., Eisenstein S.,
RA   Koundinya M., Raphael J., Moreira D., Kelley T., LaBaer J., Lin Y.,
RA   Phelan M., Farmer A.;
RT   "Cloning of human full-length CDSs in BD Creator(TM) system donor vector.";
RL   Submitted (MAY-2003) to the EMBL/GenBank/DDBJ databases.
RN   [5]
RP   NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RG   NHLBI resequencing and genotyping service (RS&G);
RL   Submitted (FEB-2007) to the EMBL/GenBank/DDBJ databases.
RN   [6]
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   [7]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC   TISSUE=Skin;
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   [8]
RP   INDUCTION.
RX   PubMed=15504365; DOI=10.1016/j.bbrc.2004.09.199;
RA   Seelan R.S., Parthasarathy L.K., Parthasarathy R.N.;
RT   "Lithium modulation of the human inositol monophosphatase 2 (IMPA2)
RT   promoter.";
RL   Biochem. Biophys. Res. Commun. 324:1370-1378(2004).
RN   [9]
RP   FUNCTION, MUTAGENESIS OF ASP-104, ACTIVITY REGULATION, COFACTOR,
RP   BIOPHYSICOCHEMICAL PROPERTIES, SUBUNIT, SUBCELLULAR LOCATION, AND CATALYTIC
RP   ACTIVITY.
RX   PubMed=17068342; DOI=10.1074/jbc.m604474200;
RA   Ohnishi T., Ohba H., Seo K.-C., Im J., Sato Y., Iwayama Y., Furuichi T.,
RA   Chung S.-K., Yoshikawa T.;
RT   "Spatial expression patterns and biochemical properties distinguish a
RT   second myo-inositol monophosphatase IMPA2 from IMPA1.";
RL   J. Biol. Chem. 282:637-646(2007).
RN   [10]
RP   IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX   PubMed=21269460; DOI=10.1186/1752-0509-5-17;
RA   Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T.,
RA   Bennett K.L., Superti-Furga G., Colinge J.;
RT   "Initial characterization of the human central proteome.";
RL   BMC Syst. Biol. 5:17-17(2011).
RN   [11]
RP   X-RAY CRYSTALLOGRAPHY (2.7 ANGSTROMS) IN COMPLEX WITH SUBSTRATE, AND
RP   HOMODIMERIZATION.
RX   PubMed=17340635; DOI=10.1002/prot.21299;
RA   Arai R., Ito K., Ohnishi T., Ohba H., Akasaka R., Bessho Y.,
RA   Hanawa-Suetsugu K., Yoshikawa T., Shirouzu M., Yokoyama S.;
RT   "Crystal structure of human myo-inositol monophosphatase 2, the product of
RT   the putative susceptibility gene for bipolar disorder, schizophrenia, and
RT   febrile seizures.";
RL   Proteins 67:732-742(2007).
RN   [12]
RP   X-RAY CRYSTALLOGRAPHY (2.4 ANGSTROMS) OF 16-288.
RG   Structural genomics consortium (SGC);
RT   "Structure of human inositol monophosphatase 2.";
RL   Submitted (FEB-2009) to the PDB data bank.
CC   -!- FUNCTION: Can use myo-inositol monophosphates, scylloinositol 1,4-
CC       diphosphate, glucose-1-phosphate, beta-glycerophosphate, and 2'-AMP as
CC       substrates. Has been implicated as the pharmacological target for
CC       lithium Li(+) action in brain. {ECO:0000269|PubMed:17068342}.
CC   -!- CATALYTIC ACTIVITY:
CC       Reaction=a myo-inositol phosphate + H2O = myo-inositol + phosphate;
CC         Xref=Rhea:RHEA:24056, ChEBI:CHEBI:15377, ChEBI:CHEBI:17268,
CC         ChEBI:CHEBI:43474, ChEBI:CHEBI:84139; EC=3.1.3.25;
CC         Evidence={ECO:0000269|PubMed:17068342};
CC   -!- COFACTOR:
CC       Name=Mg(2+); Xref=ChEBI:CHEBI:18420;
CC         Evidence={ECO:0000269|PubMed:17068342};
CC   -!- ACTIVITY REGULATION: Inhibited by high Li(+) and restricted Mg(2+)
CC       concentrations. {ECO:0000269|PubMed:17068342}.
CC   -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC       Kinetic parameters:
CC         KM=5 mM for myo-inositol 1-monophosphate
CC         {ECO:0000269|PubMed:17068342};
CC       pH dependence:
CC         Optimum pH is 7.5-8.0. {ECO:0000269|PubMed:17068342};
CC   -!- PATHWAY: Polyol metabolism; myo-inositol biosynthesis; myo-inositol
CC       from D-glucose 6-phosphate: step 2/2.
CC   -!- SUBUNIT: Homodimer. {ECO:0000269|PubMed:17068342,
CC       ECO:0000269|PubMed:17340635}.
CC   -!- INTERACTION:
CC       O14732; P29218: IMPA1; NbExp=3; IntAct=EBI-725233, EBI-752410;
CC       O14732; P29218-3: IMPA1; NbExp=3; IntAct=EBI-725233, EBI-12330251;
CC       O14732; Q8N4M1-3: SLC44A3; NbExp=3; IntAct=EBI-725233, EBI-12056955;
CC       O14732; Q8TBC4: UBA3; NbExp=6; IntAct=EBI-725233, EBI-717567;
CC   -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000269|PubMed:17068342}.
CC   -!- ALTERNATIVE PRODUCTS:
CC       Event=Alternative splicing; Named isoforms=2;
CC       Name=1;
CC         IsoId=O14732-1; Sequence=Displayed;
CC       Name=2; Synonyms=A2b;
CC         IsoId=O14732-2; Sequence=VSP_013674;
CC   -!- INDUCTION: Repressed by Li(+). {ECO:0000269|PubMed:15504365}.
CC   -!- SIMILARITY: Belongs to the inositol monophosphatase superfamily.
CC       {ECO:0000305}.
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DR   EMBL; AF014398; AAB70915.1; -; mRNA.
DR   EMBL; AF157102; AAD40683.1; -; Genomic_DNA.
DR   EMBL; AF157096; AAD40683.1; JOINED; Genomic_DNA.
DR   EMBL; AF157097; AAD40683.1; JOINED; Genomic_DNA.
DR   EMBL; AF157098; AAD40683.1; JOINED; Genomic_DNA.
DR   EMBL; AF157099; AAD40683.1; JOINED; Genomic_DNA.
DR   EMBL; AF157100; AAD40683.1; JOINED; Genomic_DNA.
DR   EMBL; AF157101; AAD40683.1; JOINED; Genomic_DNA.
DR   EMBL; AF200432; AAF07824.1; -; mRNA.
DR   EMBL; BT007061; AAP35710.1; -; mRNA.
DR   EMBL; EF444990; ACA06007.1; -; Genomic_DNA.
DR   EMBL; CH471113; EAX01559.1; -; Genomic_DNA.
DR   EMBL; BC017176; AAH17176.1; -; mRNA.
DR   CCDS; CCDS11855.1; -. [O14732-1]
DR   RefSeq; NP_055029.1; NM_014214.2. [O14732-1]
DR   PDB; 2CZH; X-ray; 2.70 A; A/B=1-288.
DR   PDB; 2CZI; X-ray; 3.00 A; A=1-288.
DR   PDB; 2CZK; X-ray; 2.90 A; A=1-288.
DR   PDB; 2DDK; X-ray; 2.70 A; A/B=1-288.
DR   PDB; 2FVZ; X-ray; 2.40 A; A/B/C/D=16-288.
DR   PDBsum; 2CZH; -.
DR   PDBsum; 2CZI; -.
DR   PDBsum; 2CZK; -.
DR   PDBsum; 2DDK; -.
DR   PDBsum; 2FVZ; -.
DR   AlphaFoldDB; O14732; -.
DR   SMR; O14732; -.
DR   BioGRID; 109826; 95.
DR   IntAct; O14732; 21.
DR   MINT; O14732; -.
DR   STRING; 9606.ENSP00000269159; -.
DR   DrugBank; DB14509; Lithium carbonate.
DR   DrugBank; DB01356; Lithium cation.
DR   DrugBank; DB14507; Lithium citrate.
DR   DrugBank; DB14508; Lithium succinate.
DR   DEPOD; IMPA2; -.
DR   iPTMnet; O14732; -.
DR   PhosphoSitePlus; O14732; -.
DR   BioMuta; IMPA2; -.
DR   EPD; O14732; -.
DR   jPOST; O14732; -.
DR   MassIVE; O14732; -.
DR   MaxQB; O14732; -.
DR   PaxDb; 9606-ENSP00000269159; -.
DR   PeptideAtlas; O14732; -.
DR   ProteomicsDB; 48190; -. [O14732-1]
DR   ProteomicsDB; 48191; -. [O14732-2]
DR   Pumba; O14732; -.
DR   TopDownProteomics; O14732-2; -. [O14732-2]
DR   Antibodypedia; 21936; 101 antibodies from 22 providers.
DR   DNASU; 3613; -.
DR   Ensembl; ENST00000269159.8; ENSP00000269159.3; ENSG00000141401.12. [O14732-1]
DR   GeneID; 3613; -.
DR   KEGG; hsa:3613; -.
DR   MANE-Select; ENST00000269159.8; ENSP00000269159.3; NM_014214.3; NP_055029.1.
DR   UCSC; uc002kqp.3; human. [O14732-1]
DR   AGR; HGNC:6051; -.
DR   CTD; 3613; -.
DR   DisGeNET; 3613; -.
DR   GeneCards; IMPA2; -.
DR   HGNC; HGNC:6051; IMPA2.
DR   HPA; ENSG00000141401; Tissue enhanced (pancreas, skeletal muscle).
DR   MIM; 605922; gene.
DR   neXtProt; NX_O14732; -.
DR   OpenTargets; ENSG00000141401; -.
DR   PharmGKB; PA29861; -.
DR   VEuPathDB; HostDB:ENSG00000141401; -.
DR   eggNOG; KOG2951; Eukaryota.
DR   GeneTree; ENSGT00940000160536; -.
DR   HOGENOM; CLU_044118_1_0_1; -.
DR   InParanoid; O14732; -.
DR   OMA; DKSHTWI; -.
DR   OrthoDB; 3685586at2759; -.
DR   PhylomeDB; O14732; -.
DR   TreeFam; TF313194; -.
DR   BioCyc; MetaCyc:HS06822-MONOMER; -.
DR   PathwayCommons; O14732; -.
DR   Reactome; R-HSA-1855183; Synthesis of IP2, IP, and Ins in the cytosol.
DR   SignaLink; O14732; -.
DR   UniPathway; UPA00823; UER00788.
DR   BioGRID-ORCS; 3613; 17 hits in 1185 CRISPR screens.
DR   ChiTaRS; IMPA2; human.
DR   EvolutionaryTrace; O14732; -.
DR   GeneWiki; IMPA2; -.
DR   GenomeRNAi; 3613; -.
DR   Pharos; O14732; Tbio.
DR   PRO; PR:O14732; -.
DR   Proteomes; UP000005640; Chromosome 18.
DR   RNAct; O14732; Protein.
DR   Bgee; ENSG00000141401; Expressed in body of pancreas and 174 other cell types or tissues.
DR   ExpressionAtlas; O14732; baseline and differential.
DR   GO; GO:0005737; C:cytoplasm; IDA:MGI.
DR   GO; GO:0005829; C:cytosol; TAS:Reactome.
DR   GO; GO:0008934; F:inositol monophosphate 1-phosphatase activity; IDA:MGI.
DR   GO; GO:0052832; F:inositol monophosphate 3-phosphatase activity; IEA:UniProtKB-EC.
DR   GO; GO:0052833; F:inositol monophosphate 4-phosphatase activity; IEA:UniProtKB-EC.
DR   GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR   GO; GO:0042803; F:protein homodimerization activity; IDA:MGI.
DR   GO; GO:0006021; P:inositol biosynthetic process; IEA:UniProtKB-UniPathway.
DR   GO; GO:0006020; P:inositol metabolic process; IBA:GO_Central.
DR   GO; GO:0006796; P:phosphate-containing compound metabolic process; TAS:ProtInc.
DR   GO; GO:0046854; P:phosphatidylinositol phosphate biosynthetic process; IEA:InterPro.
DR   GO; GO:0010226; P:response to lithium ion; IDA:UniProtKB.
DR   GO; GO:0007165; P:signal transduction; IBA:GO_Central.
DR   CDD; cd01639; IMPase; 1.
DR   Gene3D; 3.40.190.80; -; 1.
DR   Gene3D; 3.30.540.10; Fructose-1,6-Bisphosphatase, subunit A, domain 1; 1.
DR   InterPro; IPR033942; IMPase.
DR   InterPro; IPR020583; Inositol_monoP_metal-BS.
DR   InterPro; IPR020552; Inositol_monoPase_Li-sen.
DR   InterPro; IPR000760; Inositol_monophosphatase-like.
DR   InterPro; IPR020550; Inositol_monophosphatase_CS.
DR   PANTHER; PTHR20854; INOSITOL MONOPHOSPHATASE; 1.
DR   PANTHER; PTHR20854:SF29; INOSITOL MONOPHOSPHATASE 2; 1.
DR   Pfam; PF00459; Inositol_P; 1.
DR   PRINTS; PR00377; IMPHPHTASES.
DR   PRINTS; PR00378; LIIMPHPHTASE.
DR   SUPFAM; SSF56655; Carbohydrate phosphatase; 1.
DR   PROSITE; PS00629; IMP_1; 1.
DR   PROSITE; PS00630; IMP_2; 1.
DR   Genevisible; O14732; HS.
PE   1: Evidence at protein level;
KW   3D-structure; Alternative splicing; Cytoplasm; Hydrolase; Magnesium;
KW   Metal-binding; Reference proteome.
FT   CHAIN           1..288
FT                   /note="Inositol monophosphatase 2"
FT                   /id="PRO_0000142520"
FT   BINDING         81
FT                   /ligand="Mg(2+)"
FT                   /ligand_id="ChEBI:CHEBI:18420"
FT                   /ligand_label="1"
FT                   /evidence="ECO:0000250|UniProtKB:P29218"
FT   BINDING         81
FT                   /ligand="substrate"
FT                   /evidence="ECO:0000269|PubMed:17340635"
FT   BINDING         101
FT                   /ligand="Mg(2+)"
FT                   /ligand_id="ChEBI:CHEBI:18420"
FT                   /ligand_label="1"
FT                   /evidence="ECO:0000250|UniProtKB:P29218"
FT   BINDING         101
FT                   /ligand="Mg(2+)"
FT                   /ligand_id="ChEBI:CHEBI:18420"
FT                   /ligand_label="2"
FT                   /evidence="ECO:0000250|UniProtKB:P29218"
FT   BINDING         103..106
FT                   /ligand="substrate"
FT   BINDING         103
FT                   /ligand="Mg(2+)"
FT                   /ligand_id="ChEBI:CHEBI:18420"
FT                   /ligand_label="1"
FT                   /evidence="ECO:0000250|UniProtKB:P29218"
FT   BINDING         104
FT                   /ligand="Mg(2+)"
FT                   /ligand_id="ChEBI:CHEBI:18420"
FT                   /ligand_label="2"
FT                   /evidence="ECO:0000250|UniProtKB:P29218"
FT   BINDING         205..207
FT                   /ligand="substrate"
FT   BINDING         224
FT                   /ligand="substrate"
FT                   /evidence="ECO:0000269|PubMed:17340635"
FT   BINDING         231
FT                   /ligand="Mg(2+)"
FT                   /ligand_id="ChEBI:CHEBI:18420"
FT                   /ligand_label="2"
FT                   /evidence="ECO:0000250|UniProtKB:P29218"
FT   BINDING         231
FT                   /ligand="substrate"
FT                   /evidence="ECO:0000250"
FT   VAR_SEQ         6..34
FT                   /note="EDQAALAAGPWEECFQAAVQLALRAGQII -> QD (in isoform 2)"
FT                   /evidence="ECO:0000303|Ref.3"
FT                   /id="VSP_013674"
FT   VARIANT         88
FT                   /note="A -> T (in dbSNP:rs16976948)"
FT                   /id="VAR_049601"
FT   MUTAGEN         104
FT                   /note="D->N: Loss of activity."
FT                   /evidence="ECO:0000269|PubMed:17068342"
FT   HELIX           17..38
FT                   /evidence="ECO:0007829|PDB:2FVZ"
FT   HELIX           56..70
FT                   /evidence="ECO:0007829|PDB:2FVZ"
FT   STRAND          77..84
FT                   /evidence="ECO:0007829|PDB:2CZH"
FT   STRAND          97..104
FT                   /evidence="ECO:0007829|PDB:2FVZ"
FT   HELIX           106..110
FT                   /evidence="ECO:0007829|PDB:2FVZ"
FT   STRAND          117..124
FT                   /evidence="ECO:0007829|PDB:2FVZ"
FT   STRAND          127..135
FT                   /evidence="ECO:0007829|PDB:2FVZ"
FT   TURN            136..139
FT                   /evidence="ECO:0007829|PDB:2FVZ"
FT   STRAND          140..145
FT                   /evidence="ECO:0007829|PDB:2FVZ"
FT   TURN            146..148
FT                   /evidence="ECO:0007829|PDB:2CZH"
FT   STRAND          150..152
FT                   /evidence="ECO:0007829|PDB:2FVZ"
FT   HELIX           165..167
FT                   /evidence="ECO:0007829|PDB:2FVZ"
FT   STRAND          169..171
FT                   /evidence="ECO:0007829|PDB:2FVZ"
FT   HELIX           180..195
FT                   /evidence="ECO:0007829|PDB:2FVZ"
FT   STRAND          199..203
FT                   /evidence="ECO:0007829|PDB:2FVZ"
FT   HELIX           207..215
FT                   /evidence="ECO:0007829|PDB:2FVZ"
FT   STRAND          220..226
FT                   /evidence="ECO:0007829|PDB:2FVZ"
FT   HELIX           229..231
FT                   /evidence="ECO:0007829|PDB:2FVZ"
FT   HELIX           233..241
FT                   /evidence="ECO:0007829|PDB:2FVZ"
FT   STRAND          245..247
FT                   /evidence="ECO:0007829|PDB:2FVZ"
FT   STRAND          251..253
FT                   /evidence="ECO:0007829|PDB:2CZH"
FT   HELIX           256..258
FT                   /evidence="ECO:0007829|PDB:2FVZ"
FT   STRAND          260..266
FT                   /evidence="ECO:0007829|PDB:2FVZ"
FT   HELIX           267..275
FT                   /evidence="ECO:0007829|PDB:2FVZ"
SQ   SEQUENCE   288 AA;  31321 MW;  30D83FA339AC69B4 CRC64;
     MKPSGEDQAA LAAGPWEECF QAAVQLALRA GQIIRKALTE EKRVSTKTSA ADLVTETDHL
     VEDLIISELR ERFPSHRFIA EEAAASGAKC VLTHSPTWII DPIDGTCNFV HRFPTVAVSI
     GFAVRQELEF GVIYHCTEER LYTGRRGRGA FCNGQRLRVS GETDLSKALV LTEIGPKRDP
     ATLKLFLSNM ERLLHAKAHG VRVIGSSTLA LCHLASGAAD AYYQFGLHCW DLAAATVIIR
     EAGGIVIDTS GGPLDLMACR VVAASTREMA MLIAQALQTI NYGRDDEK
//