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Protein

Inositol monophosphatase 1

Gene

IMPA1

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

Functioni

Responsible for the provision of inositol required for synthesis of phosphatidylinositol and polyphosphoinositides and has been implicated as the pharmacological target for lithium action in brain. Has broad substrate specificity and can use myo-inositol monophosphates, myo-inositol 1,3-diphosphate, myo-inositol 1,4-diphosphate, scyllo-inositol-phosphate, D-galactose 1-phosphate, glucose-1-phosphate, glucose-6-phosphate, fructose-1-phosphate, beta-glycerophosphate, and 2'-AMP as substrates.3 Publications

Catalytic activityi

Myo-inositol phosphate + H2O = myo-inositol + phosphate.4 Publications
Alpha-D-galactose 1-phosphate + H2O = D-galactose + phosphate.1 Publication

Cofactori

Mg2+2 Publications3 Publications

Enzyme regulationi

Activity with myo-inositol monophosphate and D-galactose 1-phosphate is inhibited by Li+, Ca2+ and Mn2+, but also by Mg2+ at concentrations above 3 mM.3 Publications

Kineticsi

  1. KM=42 µM for D-myo-inositol 1-phosphate1 Publication
  2. KM=62 µM for L-myo-inositol 1-phosphate1 Publication

    pH dependencei

    Optimum pH is 7.0-7.5.1 Publication

    Pathwayi: 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)DescriptionActionsGraphical viewLength
    Metal bindingi70Magnesium 1; catalytic2 Publications2 Publications1
    Binding sitei70Substrate1 Publication1 Publication1
    Metal bindingi90Magnesium 1; catalytic2 Publications2 Publications1
    Metal bindingi90Magnesium 22 Publications1
    Metal bindingi92Magnesium 1; via carbonyl oxygen; catalytic2 Publications2 Publications1
    Metal bindingi93Magnesium 22 Publications1
    Binding sitei213Substrate1 Publication1 Publication1
    Metal bindingi220Magnesium 22 Publications1
    Binding sitei220Substrate1 Publication1

    GO - Molecular functioni

    • inositol monophosphate 1-phosphatase activity Source: UniProtKB
    • inositol monophosphate 3-phosphatase activity Source: Reactome
    • inositol monophosphate 4-phosphatase activity Source: Reactome
    • inositol monophosphate phosphatase activity Source: UniProtKB
    • lithium ion binding Source: UniProtKB
    • magnesium ion binding Source: UniProtKB
    • manganese ion binding Source: UniProtKB
    • protein homodimerization activity Source: MGI

    GO - Biological processi

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

    Keywords - Molecular functioni

    Hydrolase

    Keywords - Ligandi

    Lithium, Magnesium, Metal-binding

    Enzyme and pathway databases

    BioCyciMetaCyc:HS05783-MONOMER.
    ZFISH:HS05783-MONOMER.
    ReactomeiR-HSA-1855183. Synthesis of IP2, IP, and Ins in the cytosol.
    SABIO-RKP29218.
    UniPathwayiUPA00823; UER00788.

    Names & Taxonomyi

    Protein namesi
    Recommended name:
    Inositol monophosphatase 1 (EC:3.1.3.255 Publications)
    Short name:
    IMP 1
    Short name:
    IMPase 1
    Alternative name(s):
    D-galactose 1-phosphate phosphatase1 Publication (EC:3.1.3.941 Publication)
    Inositol-1(or 4)-monophosphatase 1
    Lithium-sensitive myo-inositol monophosphatase A1
    Gene namesi
    Name:IMPA1
    Synonyms:IMPA
    OrganismiHomo sapiens (Human)
    Taxonomic identifieri9606 [NCBI]
    Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
    Proteomesi
    • UP000005640 Componenti: Chromosome 8

    Organism-specific databases

    HGNCiHGNC:6050. IMPA1.

    Subcellular locationi

    GO - Cellular componenti

    • cytoplasm Source: UniProtKB
    • cytosol Source: Reactome
    • extracellular exosome Source: UniProtKB
    Complete GO annotation...

    Keywords - Cellular componenti

    Cytoplasm

    Pathology & Biotechi

    Mutagenesis

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Mutagenesisi36K → Q: 50-fold reduction in activity. 1 Publication1
    Mutagenesisi93D → N: Loss of activity. 1 Publication1
    Mutagenesisi165S → A or I: Reduced enzyme activity with myo-inositol 1-phosphate. 1 Publication1
    Mutagenesisi213E → Q: Strongly reduced affinity for myo-inositol 1-phosphate and strongly reduced enzyme activity with myo-inositol 1-phosphate. 1 Publication1

    Organism-specific databases

    DisGeNETi3612.
    OpenTargetsiENSG00000133731.
    PharmGKBiPA29860.

    Chemistry databases

    ChEMBLiCHEMBL1786.
    DrugBankiDB01356. Lithium.
    GuidetoPHARMACOLOGYi1463.

    Polymorphism and mutation databases

    BioMutaiIMPA1.
    DMDMi127717.

    PTM / Processingi

    Molecule processing

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    ChainiPRO_00001425131 – 277Inositol monophosphatase 1Add BLAST277

    Amino acid modifications

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Modified residuei168PhosphothreonineCombined sources1

    Keywords - PTMi

    Phosphoprotein

    Proteomic databases

    EPDiP29218.
    MaxQBiP29218.
    PaxDbiP29218.
    PeptideAtlasiP29218.
    PRIDEiP29218.

    2D gel databases

    REPRODUCTION-2DPAGEIPI00020906.
    UCD-2DPAGEP29218.

    PTM databases

    DEPODiP29218.
    iPTMnetiP29218.
    PhosphoSitePlusiP29218.
    SwissPalmiP29218.

    Expressioni

    Gene expression databases

    BgeeiENSG00000133731.
    CleanExiHS_IMPA1.
    ExpressionAtlasiP29218. baseline and differential.
    GenevisibleiP29218. HS.

    Organism-specific databases

    HPAiHPA037489.

    Interactioni

    Subunit structurei

    Homodimer.5 Publications

    Binary interactionsi

    WithEntry#Exp.IntActNotes
    itself4EBI-752410,EBI-752410
    IMPA2O147323EBI-752410,EBI-725233

    GO - Molecular functioni

    • protein homodimerization activity Source: MGI

    Protein-protein interaction databases

    BioGridi109825. 23 interactors.
    IntActiP29218. 3 interactors.
    MINTiMINT-1480285.
    STRINGi9606.ENSP00000408526.

    Chemistry databases

    BindingDBiP29218.

    Structurei

    Secondary structure

    1277
    Legend: HelixTurnBeta strandPDB Structure known for this area
    Show more details
    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Helixi4 – 26Combined sources23
    Beta strandi34 – 38Combined sources5
    Beta strandi41 – 43Combined sources3
    Helixi45 – 61Combined sources17
    Beta strandi66 – 69Combined sources4
    Helixi70 – 74Combined sources5
    Beta strandi86 – 93Combined sources8
    Helixi95 – 100Combined sources6
    Beta strandi106 – 113Combined sources8
    Beta strandi116 – 124Combined sources9
    Turni125 – 128Combined sources4
    Beta strandi129 – 134Combined sources6
    Turni135 – 137Combined sources3
    Beta strandi138 – 141Combined sources4
    Helixi154 – 156Combined sources3
    Beta strandi158 – 160Combined sources3
    Helixi169 – 183Combined sources15
    Turni184 – 186Combined sources3
    Beta strandi188 – 192Combined sources5
    Helixi196 – 204Combined sources9
    Beta strandi207 – 215Combined sources9
    Helixi218 – 230Combined sources13
    Beta strandi234 – 236Combined sources3
    Beta strandi240 – 242Combined sources3
    Beta strandi247 – 255Combined sources9
    Helixi256 – 265Combined sources10

    3D structure databases

    Select the link destinations:
    PDBei
    RCSB PDBi
    PDBji
    Links Updated
    PDB entryMethodResolution (Å)ChainPositionsPDBsum
    1AWBX-ray2.50A/B2-277[»]
    1IMAX-ray2.30A/B1-277[»]
    1IMBX-ray2.20A/B1-277[»]
    1IMCX-ray2.60A/B1-277[»]
    1IMDX-ray2.60A/B1-277[»]
    1IMEX-ray2.25A/B1-277[»]
    1IMFX-ray2.50A1-277[»]
    2HHMX-ray2.10A/B2-277[»]
    4AS4X-ray1.70A/B1-277[»]
    ProteinModelPortaliP29218.
    SMRiP29218.
    ModBaseiSearch...
    MobiDBiSearch...

    Miscellaneous databases

    EvolutionaryTraceiP29218.

    Family & Domainsi

    Region

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Regioni92 – 95Substrate binding1 Publication1 Publication4
    Regioni194 – 196Substrate binding1 Publication3

    Sequence similaritiesi

    Belongs to the inositol monophosphatase family.Curated

    Phylogenomic databases

    eggNOGiKOG2951. Eukaryota.
    COG0483. LUCA.
    GeneTreeiENSGT00390000014699.
    HOGENOMiHOG000282238.
    HOVERGENiHBG052123.
    InParanoidiP29218.
    KOiK01092.
    OMAiKIEFGIV.
    OrthoDBiEOG091G0D21.
    PhylomeDBiP29218.
    TreeFamiTF313194.

    Family and domain databases

    CDDicd01639. IMPase. 1 hit.
    InterProiIPR033942. IMPase.
    IPR020583. Inositol_monoP_metal-BS.
    IPR020552. Inositol_monoPase_Li-sen.
    IPR000760. Inositol_monophosphatase-like.
    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 (3)i

    Sequence statusi: Complete.

    This entry describes 3 isoformsi produced by alternative splicing. AlignAdd to basket

    Isoform 1 (identifier: P29218-1) [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
    MADPWQECMD YAVTLARQAG EVVCEAIKNE MNVMLKSSPV DLVTATDQKV
    60 70 80 90 100
    EKMLISSIKE KYPSHSFIGE ESVAAGEKSI LTDNPTWIID PIDGTTNFVH
    110 120 130 140 150
    RFPFVAVSIG FAVNKKIEFG VVYSCVEGKM YTARKGKGAF CNGQKLQVSQ
    160 170 180 190 200
    QEDITKSLLV TELGSSRTPE TVRMVLSNME KLFCIPVHGI RSVGTAAVNM
    210 220 230 240 250
    CLVATGGADA YYEMGIHCWD VAGAGIIVTE AGGVLMDVTG GPFDLMSRRV
    260 270
    IAANNRILAE RIAKEIQVIP LQRDDED
    Length:277
    Mass (Da):30,189
    Last modified:December 1, 1992 - v1
    Checksum:i861D5617E1C04627
    GO
    Isoform 2 (identifier: P29218-2) [UniParc]FASTAAdd to basket

    The sequence of this isoform differs from the canonical sequence as follows:
         153-277: DITKSLLVTE...VIPLQRDDED → GSGVLEQQLL...ALLLLKLVAC

    Note: No experimental confirmation available.
    Show »
    Length:198
    Mass (Da):21,956
    Checksum:i59A26CFDC77422ED
    GO
    Isoform 3 (identifier: P29218-3) [UniParc]FASTAAdd to basket

    The sequence of this isoform differs from the canonical sequence as follows:
         1-1: M → MGQRPGPVLPAVAVLGQVAKRKVAWLLRWKAVTRTETAGNSSGVYGFGKMKIFVKYFQKM

    Note: No experimental confirmation available.Curated
    Show »
    Length:336
    Mass (Da):36,695
    Checksum:i5838EB952D0C2FA6
    GO

    Experimental Info

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Isoform 3 (identifier: P29218-3)
    Sequence conflicti17Q → R in BAH13340 (PubMed:14702039).Curated1

    Natural variant

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Natural variantiVAR_049600109I → V.Corresponds to variant rs204781dbSNPEnsembl.1

    Alternative sequence

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Alternative sequenceiVSP_0463081M → MGQRPGPVLPAVAVLGQVAK RKVAWLLRWKAVTRTETAGN SSGVYGFGKMKIFVKYFQKM in isoform 3. 1 Publication1
    Alternative sequenceiVSP_042521153 – 277DITKS…RDDED → GSGVLEQQLLICALWQLAEQ MHIMKWEFTAGMLQELALLL LKLVAC in isoform 2. 1 PublicationAdd BLAST125

    Sequence databases

    Select the link destinations:
    EMBLi
    GenBanki
    DDBJi
    Links Updated
    X66922 mRNA. Translation: CAA47359.1.
    Y11360
    , Y11361, Y11362, Y11367, Y11363, Y11364, Y11365, Y11366 Genomic DNA. Translation: CAA72195.1.
    AF042729 mRNA. Translation: AAB97468.1.
    AK297078 mRNA. Translation: BAG59595.1.
    AK300750 mRNA. Translation: BAH13340.1.
    AK312823 mRNA. Translation: BAG35680.1.
    AC090255 Genomic DNA. No translation available.
    CH471068 Genomic DNA. Translation: EAW87095.1.
    BC008381 mRNA. Translation: AAH08381.1.
    BC009565 mRNA. Translation: AAH09565.1.
    AF178754 Genomic DNA. Translation: AAD52997.1.
    CCDSiCCDS47883.1. [P29218-3]
    CCDS47884.1. [P29218-2]
    CCDS6231.1. [P29218-1]
    PIRiS23130.
    RefSeqiNP_001138350.1. NM_001144878.1. [P29218-3]
    NP_001138351.1. NM_001144879.1. [P29218-2]
    NP_005527.1. NM_005536.3. [P29218-1]
    UniGeneiHs.656694.

    Genome annotation databases

    EnsembliENST00000256108; ENSP00000256108; ENSG00000133731. [P29218-1]
    ENST00000311489; ENSP00000311803; ENSG00000133731. [P29218-2]
    ENST00000449740; ENSP00000408526; ENSG00000133731. [P29218-3]
    GeneIDi3612.
    KEGGihsa:3612.
    UCSCiuc003ych.3. human. [P29218-1]

    Keywords - Coding sequence diversityi

    Alternative splicing, Polymorphism

    Cross-referencesi

    Sequence databases

    Select the link destinations:
    EMBLi
    GenBanki
    DDBJi
    Links Updated
    X66922 mRNA. Translation: CAA47359.1.
    Y11360
    , Y11361, Y11362, Y11367, Y11363, Y11364, Y11365, Y11366 Genomic DNA. Translation: CAA72195.1.
    AF042729 mRNA. Translation: AAB97468.1.
    AK297078 mRNA. Translation: BAG59595.1.
    AK300750 mRNA. Translation: BAH13340.1.
    AK312823 mRNA. Translation: BAG35680.1.
    AC090255 Genomic DNA. No translation available.
    CH471068 Genomic DNA. Translation: EAW87095.1.
    BC008381 mRNA. Translation: AAH08381.1.
    BC009565 mRNA. Translation: AAH09565.1.
    AF178754 Genomic DNA. Translation: AAD52997.1.
    CCDSiCCDS47883.1. [P29218-3]
    CCDS47884.1. [P29218-2]
    CCDS6231.1. [P29218-1]
    PIRiS23130.
    RefSeqiNP_001138350.1. NM_001144878.1. [P29218-3]
    NP_001138351.1. NM_001144879.1. [P29218-2]
    NP_005527.1. NM_005536.3. [P29218-1]
    UniGeneiHs.656694.

    3D structure databases

    Select the link destinations:
    PDBei
    RCSB PDBi
    PDBji
    Links Updated
    PDB entryMethodResolution (Å)ChainPositionsPDBsum
    1AWBX-ray2.50A/B2-277[»]
    1IMAX-ray2.30A/B1-277[»]
    1IMBX-ray2.20A/B1-277[»]
    1IMCX-ray2.60A/B1-277[»]
    1IMDX-ray2.60A/B1-277[»]
    1IMEX-ray2.25A/B1-277[»]
    1IMFX-ray2.50A1-277[»]
    2HHMX-ray2.10A/B2-277[»]
    4AS4X-ray1.70A/B1-277[»]
    ProteinModelPortaliP29218.
    SMRiP29218.
    ModBaseiSearch...
    MobiDBiSearch...

    Protein-protein interaction databases

    BioGridi109825. 23 interactors.
    IntActiP29218. 3 interactors.
    MINTiMINT-1480285.
    STRINGi9606.ENSP00000408526.

    Chemistry databases

    BindingDBiP29218.
    ChEMBLiCHEMBL1786.
    DrugBankiDB01356. Lithium.
    GuidetoPHARMACOLOGYi1463.

    PTM databases

    DEPODiP29218.
    iPTMnetiP29218.
    PhosphoSitePlusiP29218.
    SwissPalmiP29218.

    Polymorphism and mutation databases

    BioMutaiIMPA1.
    DMDMi127717.

    2D gel databases

    REPRODUCTION-2DPAGEIPI00020906.
    UCD-2DPAGEP29218.

    Proteomic databases

    EPDiP29218.
    MaxQBiP29218.
    PaxDbiP29218.
    PeptideAtlasiP29218.
    PRIDEiP29218.

    Protocols and materials databases

    DNASUi3612.
    Structural Biology KnowledgebaseSearch...

    Genome annotation databases

    EnsembliENST00000256108; ENSP00000256108; ENSG00000133731. [P29218-1]
    ENST00000311489; ENSP00000311803; ENSG00000133731. [P29218-2]
    ENST00000449740; ENSP00000408526; ENSG00000133731. [P29218-3]
    GeneIDi3612.
    KEGGihsa:3612.
    UCSCiuc003ych.3. human. [P29218-1]

    Organism-specific databases

    CTDi3612.
    DisGeNETi3612.
    GeneCardsiIMPA1.
    HGNCiHGNC:6050. IMPA1.
    HPAiHPA037489.
    MIMi602064. gene.
    neXtProtiNX_P29218.
    OpenTargetsiENSG00000133731.
    PharmGKBiPA29860.
    GenAtlasiSearch...

    Phylogenomic databases

    eggNOGiKOG2951. Eukaryota.
    COG0483. LUCA.
    GeneTreeiENSGT00390000014699.
    HOGENOMiHOG000282238.
    HOVERGENiHBG052123.
    InParanoidiP29218.
    KOiK01092.
    OMAiKIEFGIV.
    OrthoDBiEOG091G0D21.
    PhylomeDBiP29218.
    TreeFamiTF313194.

    Enzyme and pathway databases

    UniPathwayiUPA00823; UER00788.
    BioCyciMetaCyc:HS05783-MONOMER.
    ZFISH:HS05783-MONOMER.
    ReactomeiR-HSA-1855183. Synthesis of IP2, IP, and Ins in the cytosol.
    SABIO-RKP29218.

    Miscellaneous databases

    ChiTaRSiIMPA1. human.
    EvolutionaryTraceiP29218.
    GeneWikiiIMPA1.
    GenomeRNAii3612.
    PROiP29218.
    SOURCEiSearch...

    Gene expression databases

    BgeeiENSG00000133731.
    CleanExiHS_IMPA1.
    ExpressionAtlasiP29218. baseline and differential.
    GenevisibleiP29218. HS.

    Family and domain databases

    CDDicd01639. IMPase. 1 hit.
    InterProiIPR033942. IMPase.
    IPR020583. Inositol_monoP_metal-BS.
    IPR020552. Inositol_monoPase_Li-sen.
    IPR000760. Inositol_monophosphatase-like.
    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...

    Entry informationi

    Entry nameiIMPA1_HUMAN
    AccessioniPrimary (citable) accession number: P29218
    Secondary accession number(s): B2R733
    , B4DLN3, B7Z6Q4, J3KQT7, Q9UK71
    Entry historyi
    Integrated into UniProtKB/Swiss-Prot: December 1, 1992
    Last sequence update: December 1, 1992
    Last modified: November 30, 2016
    This is version 184 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 8
      Human chromosome 8: 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

    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 one 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.