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Protein

Inosine triphosphate pyrophosphatase

Gene

Itpa

Organism
Mus musculus (Mouse)
Status
Reviewed-Annotation score: -Experimental evidence at protein leveli

Functioni

Pyrophosphatase that hydrolyzes the non-canonical purine nucleotides inosine triphosphate (ITP), deoxyinosine triphosphate (dITP) as well as 2'-deoxy-N-6-hydroxylaminopurine triposphate (dHAPTP) and xanthosine 5'-triphosphate (XTP) to their respective monophosphate derivatives. The enzyme does not distinguish between the deoxy- and ribose forms. Probably excludes non-canonical purines from RNA and DNA precursor pools, thus preventing their incorporation into RNA and DNA and avoiding chromosomal lesions.UniRule annotation3 Publications

Catalytic activityi

A nucleoside triphosphate + H2O = a nucleotide + diphosphate.UniRule annotation2 Publications

Cofactori

Mg2+UniRule annotation, Mn2+UniRule annotationNote: Binds 1 divalent metal cation per subunit; can use either Mg2+ or Mn2+.UniRule annotation

Kineticsi

Vmax values are similar for dITP, dHAPTP and dGTP.
  1. KM=24.9 µM for dITP1 Publication
  2. KM=38.4 µM for dHAPTP1 Publication
  3. KM=667 µM for dGTP1 Publication

    Sites

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Metal bindingi44Magnesium or manganeseUniRule annotation1
    Binding sitei56SubstrateUniRule annotation1
    Metal bindingi72Magnesium or manganeseUniRule annotation1
    Binding sitei172SubstrateUniRule annotation1

    GO - Molecular functioni

    GO - Biological processi

    Keywordsi

    Molecular functionHydrolase
    Biological processNucleotide metabolism
    LigandMagnesium, Manganese, Metal-binding, Nucleotide-binding

    Enzyme and pathway databases

    ReactomeiR-MMU-74259 Purine catabolism

    Names & Taxonomyi

    Protein namesi
    Recommended name:
    Inosine triphosphate pyrophosphataseUniRule annotation (EC:3.6.1.9UniRule annotation2 Publications)
    Short name:
    ITPaseUniRule annotation
    Short name:
    Inosine triphosphataseUniRule annotation
    Alternative name(s):
    Non-canonical purine NTP pyrophosphataseUniRule annotation
    Non-standard purine NTP pyrophosphataseUniRule annotation
    Nucleoside-triphosphate diphosphataseUniRule annotation
    Nucleoside-triphosphate pyrophosphataseUniRule annotation
    Short name:
    NTPaseUniRule annotation
    Gene namesi
    Name:Itpa
    OrganismiMus musculus (Mouse)
    Taxonomic identifieri10090 [NCBI]
    Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaMyomorphaMuroideaMuridaeMurinaeMusMus
    Proteomesi
    • UP000000589 Componenti: Chromosome 2

    Organism-specific databases

    MGIiMGI:96622 Itpa

    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

    Disruption phenotypei

    Pups die about 2 weeks after birth with growth retardation and heart failure. Accumulates ITP in erythrocytes. Accumulates inosine in RNA and deoxyinosine in DNA.2 Publications

    PTM / Processingi

    Molecule processing

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Initiator methionineiRemovedUniRule annotation
    ChainiPRO_00001782812 – 198Inosine triphosphate pyrophosphataseAdd BLAST197

    Amino acid modifications

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Modified residuei2N-acetylalanineUniRule annotationBy similarity1
    Modified residuei146PhosphoserineCombined sources1

    Keywords - PTMi

    Acetylation, Phosphoprotein

    Proteomic databases

    EPDiQ9D892
    MaxQBiQ9D892
    PaxDbiQ9D892
    PRIDEiQ9D892

    2D gel databases

    REPRODUCTION-2DPAGEiQ9D892

    PTM databases

    iPTMnetiQ9D892
    PhosphoSitePlusiQ9D892
    SwissPalmiQ9D892

    Expressioni

    Gene expression databases

    BgeeiENSMUSG00000074797 Expressed in 279 organ(s), highest expression level in embryonic stem cell
    ExpressionAtlasiQ9D892 baseline and differential
    GenevisibleiQ9D892 MM

    Interactioni

    Subunit structurei

    Homodimer.UniRule annotation

    GO - Molecular functioni

    Protein-protein interaction databases

    IntActiQ9D892, 4 interactors
    MINTiQ9D892
    STRINGi10090.ENSMUSP00000099482

    Structurei

    3D structure databases

    ProteinModelPortaliQ9D892
    SMRiQ9D892
    ModBaseiSearch...
    MobiDBiSearch...

    Family & Domainsi

    Region

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Regioni14 – 19Substrate bindingUniRule annotation6
    Regioni72 – 73Substrate bindingUniRule annotation2
    Regioni149 – 152Substrate bindingUniRule annotation4
    Regioni177 – 178Substrate bindingUniRule annotation2

    Sequence similaritiesi

    Belongs to the HAM1 NTPase family.UniRule annotation

    Phylogenomic databases

    eggNOGiKOG3222 Eukaryota
    COG0127 LUCA
    GeneTreeiENSGT00390000015399
    HOGENOMiHOG000293320
    HOVERGENiHBG039521
    InParanoidiQ9D892
    KOiK01519
    OMAiYDPIFQP
    OrthoDBiEOG091G0MUD
    PhylomeDBiQ9D892
    TreeFamiTF105614

    Family and domain databases

    CDDicd00515 HAM1, 1 hit
    Gene3Di3.90.950.10, 1 hit
    HAMAPiMF_03148 HAM1_NTPase, 1 hit
    InterProiView protein in InterPro
    IPR002637 Ham1p-like
    IPR027502 ITPase
    IPR029001 ITPase-like_fam
    PANTHERiPTHR11067 PTHR11067, 1 hit
    PfamiView protein in Pfam
    PF01725 Ham1p_like, 1 hit
    SUPFAMiSSF52972 SSF52972, 1 hit
    TIGRFAMsiTIGR00042 TIGR00042, 1 hit

    Sequencei

    Sequence statusi: Complete.

    Sequence processingi: The displayed sequence is further processed into a mature form.

    Q9D892-1 [UniParc]FASTAAdd to basket
    « Hide
            10         20         30         40         50
    MAASLVGKKI VFVTGNAKKL EEVIQILGDN FPCTLEAQKI DLPEYQGEPD
    60 70 80 90 100
    EISIQKCREA ARQVQGPVLV EDTCLCFNAL GGLPGPYIKW FLQKLKPEGL
    110 120 130 140 150
    HQLLAGFEDK SAYALCTFAL STGDPSQPVL LFRGQTSGQI VMPRGSRDFG
    160 170 180 190
    WDPCFQPDGY EQTYAEMPKS EKNTISHRFR ALHKLQEYFS VAAGAGDH
    Length:198
    Mass (Da):21,897
    Last modified:April 23, 2003 - v2
    Checksum:iD70337E3D2001A9E
    GO

    Experimental Info

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Sequence conflicti32P → Q in BAB25571 (PubMed:15489334).Curated1
    Sequence conflicti54I → M in BAB25571 (PubMed:15489334).Curated1

    Sequence databases

    Select the link destinations:
    EMBLi
    GenBanki
    DDBJi
    Links Updated
    AK008279 mRNA Translation: BAB25571.1
    BC026508 mRNA Translation: AAH26508.1
    CCDSiCCDS16748.1
    RefSeqiNP_080198.2, NM_025922.2
    XP_017171220.1, XM_017315731.1
    UniGeneiMm.21399

    Genome annotation databases

    EnsembliENSMUST00000103193; ENSMUSP00000099482; ENSMUSG00000074797
    GeneIDi16434
    KEGGimmu:16434
    UCSCiuc008mju.1 mouse

    Similar proteinsi

    Cross-referencesi

    Sequence databases

    Select the link destinations:
    EMBLi
    GenBanki
    DDBJi
    Links Updated
    AK008279 mRNA Translation: BAB25571.1
    BC026508 mRNA Translation: AAH26508.1
    CCDSiCCDS16748.1
    RefSeqiNP_080198.2, NM_025922.2
    XP_017171220.1, XM_017315731.1
    UniGeneiMm.21399

    3D structure databases

    ProteinModelPortaliQ9D892
    SMRiQ9D892
    ModBaseiSearch...
    MobiDBiSearch...

    Protein-protein interaction databases

    IntActiQ9D892, 4 interactors
    MINTiQ9D892
    STRINGi10090.ENSMUSP00000099482

    PTM databases

    iPTMnetiQ9D892
    PhosphoSitePlusiQ9D892
    SwissPalmiQ9D892

    2D gel databases

    REPRODUCTION-2DPAGEiQ9D892

    Proteomic databases

    EPDiQ9D892
    MaxQBiQ9D892
    PaxDbiQ9D892
    PRIDEiQ9D892

    Protocols and materials databases

    Structural Biology KnowledgebaseSearch...

    Genome annotation databases

    EnsembliENSMUST00000103193; ENSMUSP00000099482; ENSMUSG00000074797
    GeneIDi16434
    KEGGimmu:16434
    UCSCiuc008mju.1 mouse

    Organism-specific databases

    CTDi3704
    MGIiMGI:96622 Itpa

    Phylogenomic databases

    eggNOGiKOG3222 Eukaryota
    COG0127 LUCA
    GeneTreeiENSGT00390000015399
    HOGENOMiHOG000293320
    HOVERGENiHBG039521
    InParanoidiQ9D892
    KOiK01519
    OMAiYDPIFQP
    OrthoDBiEOG091G0MUD
    PhylomeDBiQ9D892
    TreeFamiTF105614

    Enzyme and pathway databases

    ReactomeiR-MMU-74259 Purine catabolism

    Miscellaneous databases

    PROiPR:Q9D892
    SOURCEiSearch...

    Gene expression databases

    BgeeiENSMUSG00000074797 Expressed in 279 organ(s), highest expression level in embryonic stem cell
    ExpressionAtlasiQ9D892 baseline and differential
    GenevisibleiQ9D892 MM

    Family and domain databases

    CDDicd00515 HAM1, 1 hit
    Gene3Di3.90.950.10, 1 hit
    HAMAPiMF_03148 HAM1_NTPase, 1 hit
    InterProiView protein in InterPro
    IPR002637 Ham1p-like
    IPR027502 ITPase
    IPR029001 ITPase-like_fam
    PANTHERiPTHR11067 PTHR11067, 1 hit
    PfamiView protein in Pfam
    PF01725 Ham1p_like, 1 hit
    SUPFAMiSSF52972 SSF52972, 1 hit
    TIGRFAMsiTIGR00042 TIGR00042, 1 hit
    ProtoNetiSearch...

    Entry informationi

    Entry nameiITPA_MOUSE
    AccessioniPrimary (citable) accession number: Q9D892
    Secondary accession number(s): Q8R0Q8
    Entry historyiIntegrated into UniProtKB/Swiss-Prot: April 23, 2003
    Last sequence update: April 23, 2003
    Last modified: November 7, 2018
    This is version 129 of the entry and version 2 of the sequence. See complete history.
    Entry statusiReviewed (UniProtKB/Swiss-Prot)
    Annotation programChordata Protein Annotation Program

    Miscellaneousi

    Keywords - Technical termi

    Complete proteome, Reference proteome

    Documents

    1. SIMILARITY comments
      Index of protein domains and families
    2. MGD cross-references
      Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot
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    Main funding by: National Institutes of Health

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