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Protein

Inositol monophosphatase 2

Gene

IMPA2

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

Can use myo-inositol monophosphates, scylloinositol 1,4-diphosphate, glucose-1-phosphate, beta-glycerophosphate, and 2'-AMP as substrates. Has been implicated as the pharmacological target for lithium Li+ action in brain.1 Publication

Catalytic activityi

Myo-inositol phosphate + H2O = myo-inositol + phosphate.

Cofactori

Mg2+1 Publication

Enzyme regulationi

Inhibited by high Li+ and restricted Mg2+ concentrations.2 Publications

Kineticsi

  1. KM=5 mM for myo-inositol 1-monophosphate1 Publication

    pH dependencei

    Optimum pH is 7.5-8.0.1 Publication

    Pathway: myo-inositol biosynthesis

    This protein is involved in step 2 of the subpathway that synthesizes myo-inositol from D-glucose 6-phosphate.
    Proteins known to be involved in the 2 steps of the subpathway in this organism are:
    1. Inositol-3-phosphate synthase 1 (ISYNA1)
    2. Inositol monophosphatase 1 (IMPA1), Inositol monophosphatase 2 (IMPA2), Inositol monophosphatase 3 (IMPAD1)
    This subpathway is part of the pathway myo-inositol biosynthesis, which is itself part of Polyol metabolism.
    View all proteins of this organism that are known to be involved in the subpathway that synthesizes myo-inositol from D-glucose 6-phosphate, the pathway myo-inositol biosynthesis and in Polyol metabolism.

    Sites

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Metal bindingi81 – 811Magnesium 1By similarity
    Binding sitei81 – 811Substrate1 Publication
    Metal bindingi101 – 1011Magnesium 1By similarity
    Metal bindingi101 – 1011Magnesium 2By similarity
    Metal bindingi103 – 1031Magnesium 1; via carbonyl oxygenBy similarity
    Metal bindingi104 – 1041Magnesium 2By similarity
    Binding sitei224 – 2241Substrate1 Publication
    Metal bindingi231 – 2311Magnesium 2By similarity
    Binding sitei231 – 2311SubstrateBy similarity

    GO - Molecular functioni

    GO - Biological processi

    • inositol biosynthetic process Source: UniProtKB-UniPathway
    • inositol phosphate dephosphorylation Source: MGI
    • inositol phosphate metabolic process Source: Reactome
    • phosphate-containing compound metabolic process Source: ProtInc
    • phosphatidylinositol phosphorylation Source: InterPro
    • signal transduction Source: ProtInc
    • small molecule metabolic process Source: Reactome
    Complete GO annotation...

    Keywords - Molecular functioni

    Hydrolase

    Keywords - Ligandi

    Magnesium, Metal-binding

    Enzyme and pathway databases

    BioCyciMetaCyc:HS06822-MONOMER.
    ReactomeiREACT_150352. Synthesis of IP2, IP, and Ins in the cytosol.
    UniPathwayiUPA00823; UER00788.

    Names & Taxonomyi

    Protein namesi
    Recommended name:
    Inositol monophosphatase 2 (EC:3.1.3.25)
    Short name:
    IMP 2
    Short name:
    IMPase 2
    Alternative name(s):
    Inositol-1(or 4)-monophosphatase 2
    Myo-inositol monophosphatase A2
    Gene namesi
    Name:IMPA2
    Synonyms:IMP.18P
    OrganismiHomo sapiens (Human)
    Taxonomic identifieri9606 [NCBI]
    Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
    ProteomesiUP000005640 Componenti: Chromosome 18

    Organism-specific databases

    HGNCiHGNC:6051. IMPA2.

    Subcellular locationi

    GO - Cellular componenti

    • cytoplasm Source: MGI
    • cytosol Source: Reactome
    Complete GO annotation...

    Pathology & Biotechi

    Mutagenesis

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Mutagenesisi104 – 1041D → N: Loss of activity. 1 Publication

    Organism-specific databases

    PharmGKBiPA29861.

    Chemistry

    DrugBankiDB01356. Lithium.

    Polymorphism and mutation databases

    BioMutaiIMPA2.

    PTM / Processingi

    Molecule processing

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Chaini1 – 288288Inositol monophosphatase 2PRO_0000142520Add
    BLAST

    Proteomic databases

    MaxQBiO14732.
    PaxDbiO14732.
    PRIDEiO14732.

    PTM databases

    DEPODiO14732.
    PhosphoSiteiO14732.

    Expressioni

    Inductioni

    Repressed by Li+.

    Gene expression databases

    BgeeiO14732.
    CleanExiHS_IMPA2.
    ExpressionAtlasiO14732. baseline and differential.
    GenevisibleiO14732. HS.

    Organism-specific databases

    HPAiHPA029561.

    Interactioni

    Subunit structurei

    Homodimer.1 Publication

    Binary interactionsi

    WithEntry#Exp.IntActNotes
    IMPA1P292183EBI-725233,EBI-752410
    UBA3Q8TBC43EBI-725233,EBI-717567

    Protein-protein interaction databases

    BioGridi109826. 8 interactions.
    IntActiO14732. 6 interactions.
    MINTiMINT-1413243.
    STRINGi9606.ENSP00000269159.

    Structurei

    Secondary structure

    1
    288
    Legend: HelixTurnBeta strand
    Show more details
    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Helixi17 – 3822Combined sources
    Helixi56 – 7015Combined sources
    Beta strandi77 – 848Combined sources
    Beta strandi97 – 1048Combined sources
    Helixi106 – 1105Combined sources
    Beta strandi117 – 1248Combined sources
    Beta strandi127 – 1359Combined sources
    Turni136 – 1394Combined sources
    Beta strandi140 – 1456Combined sources
    Turni146 – 1483Combined sources
    Beta strandi150 – 1523Combined sources
    Helixi165 – 1673Combined sources
    Beta strandi169 – 1713Combined sources
    Helixi180 – 19516Combined sources
    Beta strandi199 – 2035Combined sources
    Helixi207 – 2159Combined sources
    Beta strandi220 – 2267Combined sources
    Helixi229 – 2313Combined sources
    Helixi233 – 2419Combined sources
    Beta strandi245 – 2473Combined sources
    Beta strandi251 – 2533Combined sources
    Helixi256 – 2583Combined sources
    Beta strandi260 – 2667Combined sources
    Helixi267 – 2759Combined sources

    3D structure databases

    Select the link destinations:
    PDBei
    RCSB PDBi
    PDBji
    Links Updated
    EntryMethodResolution (Å)ChainPositionsPDBsum
    2CZHX-ray2.70A/B1-288[»]
    2CZIX-ray3.00A1-288[»]
    2CZKX-ray2.90A1-288[»]
    2DDKX-ray2.70A/B1-288[»]
    2FVZX-ray2.40A/B/C/D16-288[»]
    ProteinModelPortaliO14732.
    SMRiO14732. Positions 15-281.
    ModBaseiSearch...
    MobiDBiSearch...

    Miscellaneous databases

    EvolutionaryTraceiO14732.

    Family & Domainsi

    Region

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Regioni103 – 1064Substrate binding
    Regioni205 – 2073Substrate binding

    Sequence similaritiesi

    Belongs to the inositol monophosphatase family.Curated

    Phylogenomic databases

    eggNOGiCOG0483.
    GeneTreeiENSGT00390000014699.
    HOGENOMiHOG000282238.
    HOVERGENiHBG052123.
    InParanoidiO14732.
    KOiK01092.
    OMAiGDPWKEC.
    OrthoDBiEOG7RJPS8.
    PhylomeDBiO14732.
    TreeFamiTF313194.

    Family and domain databases

    InterProiIPR020583. Inositol_monoP_metal-BS.
    IPR020552. Inositol_monoPase_Li-sen.
    IPR000760. Inositol_monophosphatase.
    IPR020550. Inositol_monophosphatase_CS.
    [Graphical view]
    PANTHERiPTHR20854. PTHR20854. 1 hit.
    PfamiPF00459. Inositol_P. 1 hit.
    [Graphical view]
    PRINTSiPR00377. IMPHPHTASES.
    PR00378. LIIMPHPHTASE.
    PROSITEiPS00629. IMP_1. 1 hit.
    PS00630. IMP_2. 1 hit.
    [Graphical view]

    Sequences (2)i

    Sequence statusi: Complete.

    This entry describes 2 isoformsi produced by alternative splicing. AlignAdd to basket

    Isoform 1 (identifier: O14732-1) [UniParc]FASTAAdd to basket

    This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

    « Hide

            10         20         30         40         50
    MKPSGEDQAA LAAGPWEECF QAAVQLALRA GQIIRKALTE EKRVSTKTSA
    60 70 80 90 100
    ADLVTETDHL VEDLIISELR ERFPSHRFIA EEAAASGAKC VLTHSPTWII
    110 120 130 140 150
    DPIDGTCNFV HRFPTVAVSI GFAVRQELEF GVIYHCTEER LYTGRRGRGA
    160 170 180 190 200
    FCNGQRLRVS GETDLSKALV LTEIGPKRDP ATLKLFLSNM ERLLHAKAHG
    210 220 230 240 250
    VRVIGSSTLA LCHLASGAAD AYYQFGLHCW DLAAATVIIR EAGGIVIDTS
    260 270 280
    GGPLDLMACR VVAASTREMA MLIAQALQTI NYGRDDEK
    Length:288
    Mass (Da):31,321
    Last modified:January 1, 1998 - v1
    Checksum:i30D83FA339AC69B4
    GO
    Isoform 2 (identifier: O14732-2) [UniParc]FASTAAdd to basket

    Also known as: A2b

    The sequence of this isoform differs from the canonical sequence as follows:
         6-34: EDQAALAAGPWEECFQAAVQLALRAGQII → QD

    Show »
    Length:261
    Mass (Da):28,512
    Checksum:iA9D2BC0A05D0DF2F
    GO

    Natural variant

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Natural varianti88 – 881A → T.
    Corresponds to variant rs16976948 [ dbSNP | Ensembl ].
    VAR_049601

    Alternative sequence

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Alternative sequencei6 – 3429EDQAA…AGQII → QD in isoform 2. 1 PublicationVSP_013674Add
    BLAST

    Sequence databases

    Select the link destinations:
    EMBLi
    GenBanki
    DDBJi
    Links Updated
    AF014398 mRNA. Translation: AAB70915.1.
    AF157102
    , AF157096, AF157097, AF157098, AF157099, AF157100, AF157101 Genomic DNA. Translation: AAD40683.1.
    AF200432 mRNA. Translation: AAF07824.1.
    BT007061 mRNA. Translation: AAP35710.1.
    EF444990 Genomic DNA. Translation: ACA06007.1.
    CH471113 Genomic DNA. Translation: EAX01559.1.
    BC017176 mRNA. Translation: AAH17176.1.
    CCDSiCCDS11855.1. [O14732-1]
    RefSeqiNP_055029.1. NM_014214.2. [O14732-1]
    UniGeneiHs.743311.

    Genome annotation databases

    EnsembliENST00000269159; ENSP00000269159; ENSG00000141401. [O14732-1]
    GeneIDi3613.
    KEGGihsa:3613.
    UCSCiuc002kqp.2. human. [O14732-1]

    Keywords - Coding sequence diversityi

    Alternative splicing, Polymorphism

    Cross-referencesi

    Sequence databases

    Select the link destinations:
    EMBLi
    GenBanki
    DDBJi
    Links Updated
    AF014398 mRNA. Translation: AAB70915.1.
    AF157102
    , AF157096, AF157097, AF157098, AF157099, AF157100, AF157101 Genomic DNA. Translation: AAD40683.1.
    AF200432 mRNA. Translation: AAF07824.1.
    BT007061 mRNA. Translation: AAP35710.1.
    EF444990 Genomic DNA. Translation: ACA06007.1.
    CH471113 Genomic DNA. Translation: EAX01559.1.
    BC017176 mRNA. Translation: AAH17176.1.
    CCDSiCCDS11855.1. [O14732-1]
    RefSeqiNP_055029.1. NM_014214.2. [O14732-1]
    UniGeneiHs.743311.

    3D structure databases

    Select the link destinations:
    PDBei
    RCSB PDBi
    PDBji
    Links Updated
    EntryMethodResolution (Å)ChainPositionsPDBsum
    2CZHX-ray2.70A/B1-288[»]
    2CZIX-ray3.00A1-288[»]
    2CZKX-ray2.90A1-288[»]
    2DDKX-ray2.70A/B1-288[»]
    2FVZX-ray2.40A/B/C/D16-288[»]
    ProteinModelPortaliO14732.
    SMRiO14732. Positions 15-281.
    ModBaseiSearch...
    MobiDBiSearch...

    Protein-protein interaction databases

    BioGridi109826. 8 interactions.
    IntActiO14732. 6 interactions.
    MINTiMINT-1413243.
    STRINGi9606.ENSP00000269159.

    Chemistry

    ChEMBLiCHEMBL1776.
    DrugBankiDB01356. Lithium.

    PTM databases

    DEPODiO14732.
    PhosphoSiteiO14732.

    Polymorphism and mutation databases

    BioMutaiIMPA2.

    Proteomic databases

    MaxQBiO14732.
    PaxDbiO14732.
    PRIDEiO14732.

    Protocols and materials databases

    DNASUi3613.
    Structural Biology KnowledgebaseSearch...

    Genome annotation databases

    EnsembliENST00000269159; ENSP00000269159; ENSG00000141401. [O14732-1]
    GeneIDi3613.
    KEGGihsa:3613.
    UCSCiuc002kqp.2. human. [O14732-1]

    Organism-specific databases

    CTDi3613.
    GeneCardsiGC18P011981.
    HGNCiHGNC:6051. IMPA2.
    HPAiHPA029561.
    MIMi605922. gene.
    neXtProtiNX_O14732.
    PharmGKBiPA29861.
    GenAtlasiSearch...

    Phylogenomic databases

    eggNOGiCOG0483.
    GeneTreeiENSGT00390000014699.
    HOGENOMiHOG000282238.
    HOVERGENiHBG052123.
    InParanoidiO14732.
    KOiK01092.
    OMAiGDPWKEC.
    OrthoDBiEOG7RJPS8.
    PhylomeDBiO14732.
    TreeFamiTF313194.

    Enzyme and pathway databases

    UniPathwayiUPA00823; UER00788.
    BioCyciMetaCyc:HS06822-MONOMER.
    ReactomeiREACT_150352. Synthesis of IP2, IP, and Ins in the cytosol.

    Miscellaneous databases

    ChiTaRSiIMPA2. human.
    EvolutionaryTraceiO14732.
    GeneWikiiIMPA2.
    GenomeRNAii3613.
    NextBioi14131.
    PROiO14732.
    SOURCEiSearch...

    Gene expression databases

    BgeeiO14732.
    CleanExiHS_IMPA2.
    ExpressionAtlasiO14732. baseline and differential.
    GenevisibleiO14732. HS.

    Family and domain databases

    InterProiIPR020583. Inositol_monoP_metal-BS.
    IPR020552. Inositol_monoPase_Li-sen.
    IPR000760. Inositol_monophosphatase.
    IPR020550. Inositol_monophosphatase_CS.
    [Graphical view]
    PANTHERiPTHR20854. PTHR20854. 1 hit.
    PfamiPF00459. Inositol_P. 1 hit.
    [Graphical view]
    PRINTSiPR00377. IMPHPHTASES.
    PR00378. LIIMPHPHTASE.
    PROSITEiPS00629. IMP_1. 1 hit.
    PS00630. IMP_2. 1 hit.
    [Graphical view]
    ProtoNetiSearch...

    Publicationsi

    « Hide 'large scale' publications
    1. "A novel human myo-inositol monophosphatase gene, IMP.18p, maps to a susceptibility region for bipolar disorder."
      Yoshikawa T., Turner G., Esterling L.E., Sanders A.R., Detera-Wadleigh S.D.
      Mol. Psychiatry 2:393-397(1997) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
    2. "A human myo-inositol monophosphatase gene (IMPA2) localized in a putative susceptibility region for bipolar disorder on chromosome 18p11.2: genomic structure and polymorphism screening in manic-depressive patients."
      Sjoeholt G., Gulbrandsen A.K., Lovlie R., Berle J., Molven A., Steen V.M.
      Mol. Psychiatry 5:172-180(2000) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
    3. "Molecular characterization of a novel form of human brain inositol monophosphatase A2b."
      Parthasarathy L., Parthasarathy R.
      Submitted (OCT-1999) to the EMBL/GenBank/DDBJ databases
      Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2).
    4. "Cloning of human full-length CDSs in BD Creator(TM) system donor vector."
      Kalnine N., Chen X., Rolfs A., Halleck A., Hines L., Eisenstein S., Koundinya M., Raphael J., Moreira D., Kelley T., LaBaer J., Lin Y., Phelan M., Farmer A.
      Submitted (MAY-2003) to the EMBL/GenBank/DDBJ databases
      Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
    5. NHLBI resequencing and genotyping service (RS&G)
      Submitted (FEB-2007) to the EMBL/GenBank/DDBJ databases
      Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
    6. Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
    7. "The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
      The MGC Project Team
      Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
      Tissue: Skin.
    8. "Lithium modulation of the human inositol monophosphatase 2 (IMPA2) promoter."
      Seelan R.S., Parthasarathy L.K., Parthasarathy R.N.
      Biochem. Biophys. Res. Commun. 324:1370-1378(2004) [PubMed] [Europe PMC] [Abstract]
      Cited for: ENZYME REGULATION.
    9. "Spatial expression patterns and biochemical properties distinguish a second myo-inositol monophosphatase IMPA2 from IMPA1."
      Ohnishi T., Ohba H., Seo K.-C., Im J., Sato Y., Iwayama Y., Furuichi T., Chung S.-K., Yoshikawa T.
      J. Biol. Chem. 282:637-646(2007) [PubMed] [Europe PMC] [Abstract]
      Cited for: FUNCTION, MUTAGENESIS OF ASP-104, ENZYME REGULATION, COFACTOR, BIOPHYSICOCHEMICAL PROPERTIES, HOMODIMERIZATION.
    10. Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
    11. "Crystal structure of human myo-inositol monophosphatase 2, the product of the putative susceptibility gene for bipolar disorder, schizophrenia, and febrile seizures."
      Arai R., Ito K., Ohnishi T., Ohba H., Akasaka R., Bessho Y., Hanawa-Suetsugu K., Yoshikawa T., Shirouzu M., Yokoyama S.
      Proteins 67:732-742(2007) [PubMed] [Europe PMC] [Abstract]
      Cited for: X-RAY CRYSTALLOGRAPHY (2.7 ANGSTROMS) IN COMPLEX WITH SUBSTRATE, HOMODIMERIZATION.
    12. "Structure of human inositol monophosphatase 2."
      Structural genomics consortium (SGC)
      Submitted (FEB-2009) to the PDB data bank
      Cited for: X-RAY CRYSTALLOGRAPHY (2.4 ANGSTROMS) OF 16-288.

    Entry informationi

    Entry nameiIMPA2_HUMAN
    AccessioniPrimary (citable) accession number: O14732
    Secondary accession number(s): B0YJ29, Q9UJT3
    Entry historyi
    Integrated into UniProtKB/Swiss-Prot: December 15, 1998
    Last sequence update: January 1, 1998
    Last modified: June 24, 2015
    This is version 137 of the entry and version 1 of the sequence. [Complete history]
    Entry statusiReviewed (UniProtKB/Swiss-Prot)
    Annotation programChordata Protein Annotation Program
    DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

    Miscellaneousi

    Keywords - Technical termi

    3D-structure, Complete proteome, Reference proteome

    Documents

    1. Human chromosome 18
      Human chromosome 18: entries, gene names and cross-references to MIM
    2. Human entries with polymorphisms or disease mutations
      List of human entries with polymorphisms or disease mutations
    3. Human polymorphisms and disease mutations
      Index of human polymorphisms and disease mutations
    4. MIM cross-references
      Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
    5. PATHWAY comments
      Index of metabolic and biosynthesis pathways
    6. PDB cross-references
      Index of Protein Data Bank (PDB) cross-references
    7. SIMILARITY comments
      Index of protein domains and families

    External Data

    Dasty 3

    Similar proteinsi

    Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
    100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into Uniref entry.
    90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
    50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.