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Protein

Diphosphoinositol polyphosphate phosphohydrolase 3-alpha

Gene

NUDT10

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

Functioni

Cleaves a beta-phosphate from the diphosphate groups in PP-InsP5 (diphosphoinositol pentakisphosphate), suggesting that it may play a role in signal transduction. Also able to catalyze the hydrolysis of dinucleoside oligophosphates, with Ap6A and Ap5A being the preferred substrates. The major reaction products are ADP and p4a from Ap6A and ADP and ATP from Ap5A. Also able to hydrolyze 5-phosphoribose 1-diphosphate.1 Publication

Catalytic activityi

Diphospho-myo-inositol polyphosphate + H2O = myo-inositol polyphosphate + phosphate.3 Publications
P1,P6-bis(5'-adenosyl)hexaphosphate + H2O = adenosine 5'-pentaphosphate + AMP.3 Publications
P1,P5-bis(5'-adenosyl)pentaphosphate + H2O = adenosine 5'-tetraphosphate + AMP.3 Publications

Cofactori

Mg2+By similarity1 Publication, Mn2+By similarity1 PublicationNote: Binds 3 Mg2+ or Mn2+ ions per subunit. Mn2+ may be the true cofactor in vivo.By similarity1 Publication

Kineticsi

  1. KM=0.088 µM for PP-InsP52 Publications
  2. KM=19 µM for Ap6A2 Publications
  3. KM=50 µM for Ap5A2 Publications

    pH dependencei

    Optimum pH is 8.5.2 Publications

    Sites

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Binding sitei9SubstrateBy similarity1
    Binding sitei40SubstrateBy similarity1
    Metal bindingi49Magnesium 1; via carbonyl oxygenBy similarity1
    Metal bindingi65Magnesium 2By similarity1
    Metal bindingi65Magnesium 3By similarity1
    Active sitei68Proton acceptorBy similarity1
    Metal bindingi69Magnesium 1By similarity1

    GO - Molecular functioni

    GO - Biological processi

    Keywordsi

    Molecular functionHydrolase
    LigandMagnesium, Manganese, Metal-binding

    Enzyme and pathway databases

    BioCyciMetaCyc:HS04604-MONOMER
    BRENDAi3.6.1.60 2681
    ReactomeiR-HSA-1855167 Synthesis of pyrophosphates in the cytosol

    Names & Taxonomyi

    Protein namesi
    Recommended name:
    Diphosphoinositol polyphosphate phosphohydrolase 3-alpha1 Publication (EC:3.6.1.523 Publications)
    Short name:
    DIPP-3-alpha
    Short name:
    DIPP3-alpha1 Publication
    Short name:
    hDIPP3alpha1 Publication
    Alternative name(s):
    Diadenosine 5',5'''-P1,P6-hexaphosphate hydrolase 3-alpha
    Diadenosine hexaphosphate hydrolase (AMP-forming) (EC:3.6.1.603 Publications)
    Nucleoside diphosphate-linked moiety X motif 10
    Short name:
    Nudix motif 10
    hAps2
    Gene namesi
    Name:NUDT10
    Synonyms:APS2, DIPP3A
    OrganismiHomo sapiens (Human)
    Taxonomic identifieri9606 [NCBI]
    Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
    Proteomesi
    • UP000005640 Componenti: Chromosome X

    Organism-specific databases

    EuPathDBiHostDB:ENSG00000122824.10
    HGNCiHGNC:17621 NUDT10
    MIMi300527 gene
    neXtProtiNX_Q8NFP7

    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

    Organism-specific databases

    DisGeNETi170685
    OpenTargetsiENSG00000122824
    PharmGKBiPA31831

    Polymorphism and mutation databases

    BioMutaiNUDT10
    DMDMi68565913

    PTM / Processingi

    Molecule processing

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    ChainiPRO_00000570621 – 164Diphosphoinositol polyphosphate phosphohydrolase 3-alphaAdd BLAST164

    Proteomic databases

    EPDiQ8NFP7
    MaxQBiQ8NFP7
    PaxDbiQ8NFP7
    PeptideAtlasiQ8NFP7
    PRIDEiQ8NFP7

    PTM databases

    iPTMnetiQ8NFP7
    PhosphoSitePlusiQ8NFP7

    Expressioni

    Tissue specificityi

    Mainly expressed in testis and, at lower level in brain. According to PubMed:12121577, it is widely expressed.2 Publications

    Gene expression databases

    BgeeiENSG00000122824
    CleanExiHS_NUDT10
    GenevisibleiQ8NFP7 HS

    Organism-specific databases

    HPAiHPA047027
    HPA057684

    Interactioni

    Binary interactionsi

    Show more details

    Protein-protein interaction databases

    BioGridi128079, 10 interactors
    IntActiQ8NFP7, 10 interactors
    STRINGi9606.ENSP00000348831

    Structurei

    Secondary structure

    1164
    Legend: HelixTurnBeta strandPDB Structure known for this area
    Show more details
    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Beta strandi18 – 27Combined sources10
    Beta strandi32 – 37Combined sources6
    Beta strandi39 – 41Combined sources3
    Beta strandi44 – 46Combined sources3
    Beta strandi49 – 51Combined sources3
    Helixi58 – 70Combined sources13
    Beta strandi72 – 83Combined sources12
    Beta strandi92 – 103Combined sources12
    Helixi108 – 113Combined sources6
    Beta strandi117 – 121Combined sources5
    Helixi122 – 130Combined sources9
    Helixi134 – 144Combined sources11

    3D structure databases

    Select the link destinations:
    PDBei
    RCSB PDBi
    PDBji
    Links Updated
    PDB entryMethodResolution (Å)ChainPositionsPDBsum
    3MCFX-ray2.00A/B17-144[»]
    ProteinModelPortaliQ8NFP7
    SMRiQ8NFP7
    ModBaseiSearch...
    MobiDBiSearch...

    Miscellaneous databases

    EvolutionaryTraceiQ8NFP7

    Family & Domainsi

    Domains and Repeats

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Domaini17 – 144Nudix hydrolasePROSITE-ProRule annotationAdd BLAST128

    Region

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Regioni17 – 19Substrate bindingBy similarity3
    Regioni89 – 91Substrate bindingBy similarity3

    Motif

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Motifi50 – 71Nudix boxAdd BLAST22

    Sequence similaritiesi

    Belongs to the Nudix hydrolase family. DIPP subfamily.Curated

    Phylogenomic databases

    eggNOGiKOG2839 Eukaryota
    COG0494 LUCA
    GeneTreeiENSGT00390000012928
    HOGENOMiHOG000237336
    HOVERGENiHBG053341
    InParanoidiQ8NFP7
    KOiK07766
    OMAiSKRHNMV
    OrthoDBiEOG091G0TH6
    PhylomeDBiQ8NFP7
    TreeFamiTF106349

    Family and domain databases

    InterProiView protein in InterPro
    IPR015797 NUDIX_hydrolase-like_dom_sf
    IPR020084 NUDIX_hydrolase_CS
    IPR000086 NUDIX_hydrolase_dom
    PfamiView protein in Pfam
    PF00293 NUDIX, 1 hit
    SUPFAMiSSF55811 SSF55811, 1 hit
    PROSITEiView protein in PROSITE
    PS51462 NUDIX, 1 hit
    PS00893 NUDIX_BOX, 1 hit

    Sequencei

    Sequence statusi: Complete.

    Q8NFP7-1 [UniParc]FASTAAdd to basket

    « Hide

            10         20         30         40         50
    MKCKPNQTRT YDPEGFKKRA ACLCFRSERE DEVLLVSSSR YPDRWIVPGG
    60 70 80 90 100
    GMEPEEEPGG AAVREVYEEA GVKGKLGRLL GVFEQNQDPK HRTYVYVLTV
    110 120 130 140 150
    TELLEDWEDS VSIGRKREWF KVEDAIKVLQ CHKPVHAEYL EKLKLGGSPT
    160
    NGNSMAPSSP DSDP
    Length:164
    Mass (Da):18,500
    Last modified:October 1, 2002 - v1
    Checksum:i589F342E02B285A7
    GO

    Experimental Info

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Sequence conflicti90K → E in AAH50700 (PubMed:15489334).Curated1
    Sequence conflicti135V → M in AAH49383 (PubMed:15489334).Curated1

    Sequence databases

    Select the link destinations:
    EMBLi
    GenBanki
    DDBJi
    Links Updated
    AF469196 mRNA Translation: AAM64113.1
    AK291952 mRNA Translation: BAF84641.1
    AL158055 Genomic DNA No translation available.
    CH471180 Genomic DNA Translation: EAW89910.1
    CH471180 Genomic DNA Translation: EAW89911.1
    BC049383 mRNA Translation: AAH49383.1
    BC050700 mRNA Translation: AAH50700.1
    CCDSiCCDS35278.1
    RefSeqiNP_001291892.1, NM_001304963.1
    NP_694853.1, NM_153183.3
    UniGeneiHs.375178

    Genome annotation databases

    EnsembliENST00000356450; ENSP00000348831; ENSG00000122824
    ENST00000376006; ENSP00000365174; ENSG00000122824
    GeneIDi170685
    KEGGihsa:170685
    UCSCiuc004dph.3 human

    Similar proteinsi

    Entry informationi

    Entry nameiNUD10_HUMAN
    AccessioniPrimary (citable) accession number: Q8NFP7
    Secondary accession number(s): A8K7D7
    , D3DX69, Q86VK1, Q86VR0
    Entry historyiIntegrated into UniProtKB/Swiss-Prot: July 5, 2005
    Last sequence update: October 1, 2002
    Last modified: March 28, 2018
    This is version 135 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
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    Main funding by: National Institutes of Health