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Protein

Inositol monophosphatase 1

Gene

IMPA1

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: -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

Caution

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-1-monophosphatase (IMPA1), Inositol-1-monophosphatase (IMPA1), Inositol-1-monophosphatase, Inositol monophosphatase 1 (IMPA1), Inositol-1-monophosphatase (IMPA1), Inositol monophosphatase 2 (IMPA2), Inositol monophosphatase 3 (IMPAD1), Inositol-1-monophosphatase (IMPA1)
    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

    • identical protein binding Source: IntAct
    • inositol monophosphate 1-phosphatase activity Source: MGI
    • 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

    Keywordsi

    Molecular functionHydrolase
    LigandLithium, Magnesium, Metal-binding

    Enzyme and pathway databases

    BioCyciMetaCyc:HS05783-MONOMER
    ReactomeiR-HSA-1855183 Synthesis of IP2, IP, and Ins in the cytosol
    SABIO-RKiP29218
    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

    EuPathDBiHostDB:ENSG00000133731.9
    HGNCiHGNC:6050 IMPA1
    MIMi602064 gene
    neXtProtiNX_P29218

    Subcellular locationi

    Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

    Keywords - Cellular componenti

    Cytoplasm

    Pathology & Biotechi

    Involvement in diseasei

    Mental retardation, autosomal recessive 59 (MRT59)1 Publication
    The disease is caused by mutations affecting the gene represented in this entry.
    Disease descriptionA form of mental retardation, a disorder characterized by significantly below average general intellectual functioning associated with impairments in adaptive behavior and manifested during the developmental period. MRT59 transmission pattern is consistent with autosomal recessive inheritance.
    See also OMIM:617323

    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

    Keywords - Diseasei

    Mental retardation

    Organism-specific databases

    DisGeNETi3612
    MIMi617323 phenotype
    OpenTargetsiENSG00000133731
    PharmGKBiPA29860

    Chemistry databases

    ChEMBLiCHEMBL1786
    DrugBankiDB03542 L-Myo-Inositol-1-Phosphate
    DB01356 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-2DPAGEiIPI00020906
    UCD-2DPAGEiP29218

    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

    Show more details

    GO - Molecular functioni

    • identical protein binding Source: IntAct
    • protein homodimerization activity Source: MGI

    Protein-protein interaction databases

    BioGridi10982523 interactors.
    IntActiP29218 4 interactors.
    MINTiP29218
    STRINGi9606.ENSP00000408526

    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

    Phylogenomic databases

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

    Family and domain databases

    CDDicd01639 IMPase, 1 hit
    InterProiView protein in InterPro
    IPR033942 IMPase
    IPR020583 Inositol_monoP_metal-BS
    IPR020552 Inositol_monoPase_Li-sen
    IPR000760 Inositol_monophosphatase-like
    IPR020550 Inositol_monophosphatase_CS
    PfamiView protein in Pfam
    PF00459 Inositol_P, 1 hit
    PRINTSiPR00377 IMPHPHTASES
    PR00378 LIIMPHPHTASE
    PROSITEiView protein in PROSITE
    PS00629 IMP_1, 1 hit
    PS00630 IMP_2, 1 hit

    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 dbSNP:rs204781Ensembl.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

    Similar proteinsi

    Entry informationi

    Entry nameiIMPA1_HUMAN
    AccessioniPrimary (citable) accession number: P29218
    Secondary accession number(s): B2R733
    , B4DLN3, B7Z6Q4, J3KQT7, Q9UK71
    Entry historyiIntegrated into UniProtKB/Swiss-Prot: December 1, 1992
    Last sequence update: December 1, 1992
    Last modified: March 28, 2018
    This is version 195 of the entry and version 1 of the sequence. See 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