IMPA2_HUMAN
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 03-AUG-2022, entry version 184.
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; 90.
DR IntAct; O14732; 19.
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; O14732; -.
DR PeptideAtlas; O14732; -.
DR PRIDE; O14732; -.
DR ProteomicsDB; 48190; -. [O14732-1]
DR ProteomicsDB; 48191; -. [O14732-2]
DR TopDownProteomics; O14732-2; -. [O14732-2]
DR Antibodypedia; 21936; 94 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 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; VHQELEF; -.
DR OrthoDB; 915621at2759; -.
DR PhylomeDB; O14732; -.
DR TreeFam; TF313194; -.
DR BioCyc; MetaCyc:HS06822-MON; -.
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; 13 hits in 1083 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 172 other tissues.
DR ExpressionAtlas; O14732; baseline and differential.
DR Genevisible; O14732; HS.
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:0046855; P:inositol phosphate dephosphorylation; IDA:MGI.
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 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 Pfam; PF00459; Inositol_P; 1.
DR PRINTS; PR00377; IMPHPHTASES.
DR PRINTS; PR00378; LIIMPHPHTASE.
DR PROSITE; PS00629; IMP_1; 1.
DR PROSITE; PS00630; IMP_2; 1.
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
