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Protein

Inosine triphosphate pyrophosphatase

Gene

Itpa

Organism
Mus musculus (Mouse)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-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

    • dITP diphosphatase activity Source: MGI
    • ITP diphosphatase activity Source: MGI
    • metal ion binding Source: UniProtKB-KW
    • NADH pyrophosphatase activity Source: UniProtKB-EC
    • nucleoside-triphosphate diphosphatase activity Source: MGI
    • nucleotide binding Source: UniProtKB-KW
    • XTP diphosphatase activity Source: MGI

    GO - Biological processi

    • chromosome organization Source: MGI
    • deoxyribonucleoside triphosphate catabolic process Source: UniProtKB-HAMAP
    • ITP catabolic process Source: MGI
    Complete GO annotation...

    Keywords - Molecular functioni

    Hydrolase

    Keywords - Biological processi

    Nucleotide metabolism

    Keywords - Ligandi

    Magnesium, Manganese, Metal-binding, Nucleotide-binding

    Enzyme and pathway databases

    ReactomeiR-MMU-15869. Metabolism of nucleotides.

    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 lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus
    Proteomesi
    • UP000000589 Componenti: Chromosome 2

    Organism-specific databases

    MGIiMGI:96622. Itpa.

    Subcellular locationi

    • Cytoplasm UniRule annotation

    GO - Cellular componenti

    Complete GO annotation...

    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-2DPAGEQ9D892.

    PTM databases

    iPTMnetiQ9D892.
    PhosphoSitePlusiQ9D892.

    Expressioni

    Gene expression databases

    BgeeiENSMUSG00000074797.
    ExpressionAtlasiQ9D892. baseline and differential.
    GenevisibleiQ9D892. MM.

    Interactioni

    Subunit structurei

    Homodimer.UniRule annotation

    Protein-protein interaction databases

    IntActiQ9D892. 4 interactors.
    MINTiMINT-1770686.
    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.
    OMAiMKIYFAT.
    OrthoDBiEOG091G0MUD.
    PhylomeDBiQ9D892.
    TreeFamiTF105614.

    Family and domain databases

    CDDicd00515. HAM1. 1 hit.
    Gene3Di3.90.950.10. 1 hit.
    HAMAPiMF_03148. HAM1_NTPase. 1 hit.
    InterProiIPR002637. Ham1p-like.
    IPR027502. ITPase.
    IPR029001. ITPase-like_fam.
    [Graphical view]
    PANTHERiPTHR11067. PTHR11067. 1 hit.
    PfamiPF01725. Ham1p_like. 1 hit.
    [Graphical view]
    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.

    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.
    MINTiMINT-1770686.
    STRINGi10090.ENSMUSP00000099482.

    PTM databases

    iPTMnetiQ9D892.
    PhosphoSitePlusiQ9D892.

    2D gel databases

    REPRODUCTION-2DPAGEQ9D892.

    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.
    OMAiMKIYFAT.
    OrthoDBiEOG091G0MUD.
    PhylomeDBiQ9D892.
    TreeFamiTF105614.

    Enzyme and pathway databases

    ReactomeiR-MMU-15869. Metabolism of nucleotides.

    Miscellaneous databases

    PROiQ9D892.
    SOURCEiSearch...

    Gene expression databases

    BgeeiENSMUSG00000074797.
    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.
    InterProiIPR002637. Ham1p-like.
    IPR027502. ITPase.
    IPR029001. ITPase-like_fam.
    [Graphical view]
    PANTHERiPTHR11067. PTHR11067. 1 hit.
    PfamiPF01725. Ham1p_like. 1 hit.
    [Graphical view]
    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 historyi
    Integrated into UniProtKB/Swiss-Prot: April 23, 2003
    Last sequence update: April 23, 2003
    Last modified: November 30, 2016
    This is version 120 of the entry and version 2 of the sequence. [Complete history]
    Entry statusiReviewed (UniProtKB/Swiss-Prot)
    Annotation programChordata Protein Annotation Program

    Miscellaneousi

    Keywords - Technical termi

    Complete proteome, Reference proteome

    Documents

    1. MGD cross-references
      Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot
    2. 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.