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Protein

Diphosphoinositol polyphosphate phosphohydrolase 3-alpha

Gene

NUDT10

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-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,P(6)-bis(5'-adenosyl)hexaphosphate + H2O = adenosine 5'-pentaphosphate + AMP.3 Publications
P1,P(5)-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

    Complete GO annotation...

    Keywords - Molecular functioni

    Hydrolase

    Keywords - Ligandi

    Magnesium, Manganese, Metal-binding

    Enzyme and pathway databases

    BioCyciMetaCyc:HS04604-MONOMER.
    ZFISH: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

    HGNCiHGNC:17621. NUDT10.

    Subcellular locationi

    • Cytoplasm 1 Publication

    GO - Cellular componenti

    Complete GO annotation...

    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

    WithEntry#Exp.IntActNotes
    MTUS2Q5JR593EBI-726826,EBI-742948
    SNAPC5O759713EBI-726826,EBI-749483
    TCF4P158843EBI-726826,EBI-533224

    Protein-protein interaction databases

    BioGridi128079. 3 interactors.
    IntActiQ8NFP7. 9 interactors.
    MINTiMINT-1383448.
    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
    Contains 1 nudix hydrolase domain.PROSITE-ProRule annotation

    Phylogenomic databases

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

    Family and domain databases

    Gene3Di3.90.79.10. 1 hit.
    InterProiIPR020084. NUDIX_hydrolase_CS.
    IPR000086. NUDIX_hydrolase_dom.
    IPR015797. NUDIX_hydrolase_dom-like.
    [Graphical view]
    PfamiPF00293. NUDIX. 1 hit.
    [Graphical view]
    SUPFAMiSSF55811. SSF55811. 1 hit.
    PROSITEiPS51462. NUDIX. 1 hit.
    PS00893. NUDIX_BOX. 1 hit.
    [Graphical view]

    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. Translation: CAI40295.1.
    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.

    Cross-referencesi

    Sequence databases

    Select the link destinations:
    EMBLi
    GenBanki
    DDBJi
    Links Updated
    AF469196 mRNA. Translation: AAM64113.1.
    AK291952 mRNA. Translation: BAF84641.1.
    AL158055 Genomic DNA. Translation: CAI40295.1.
    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.

    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...

    Protein-protein interaction databases

    BioGridi128079. 3 interactors.
    IntActiQ8NFP7. 9 interactors.
    MINTiMINT-1383448.
    STRINGi9606.ENSP00000348831.

    PTM databases

    iPTMnetiQ8NFP7.
    PhosphoSitePlusiQ8NFP7.

    Polymorphism and mutation databases

    BioMutaiNUDT10.
    DMDMi68565913.

    Proteomic databases

    EPDiQ8NFP7.
    MaxQBiQ8NFP7.
    PaxDbiQ8NFP7.
    PeptideAtlasiQ8NFP7.
    PRIDEiQ8NFP7.

    Protocols and materials databases

    DNASUi170685.
    Structural Biology KnowledgebaseSearch...

    Genome annotation databases

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

    Organism-specific databases

    CTDi170685.
    DisGeNETi170685.
    GeneCardsiNUDT10.
    HGNCiHGNC:17621. NUDT10.
    HPAiHPA047027.
    HPA057684.
    MIMi300527. gene.
    neXtProtiNX_Q8NFP7.
    OpenTargetsiENSG00000122824.
    PharmGKBiPA31831.
    GenAtlasiSearch...

    Phylogenomic databases

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

    Enzyme and pathway databases

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

    Miscellaneous databases

    ChiTaRSiNUDT10. human.
    EvolutionaryTraceiQ8NFP7.
    GenomeRNAii170685.
    PROiQ8NFP7.
    SOURCEiSearch...

    Gene expression databases

    BgeeiENSG00000122824.
    CleanExiHS_NUDT10.
    GenevisibleiQ8NFP7. HS.

    Family and domain databases

    Gene3Di3.90.79.10. 1 hit.
    InterProiIPR020084. NUDIX_hydrolase_CS.
    IPR000086. NUDIX_hydrolase_dom.
    IPR015797. NUDIX_hydrolase_dom-like.
    [Graphical view]
    PfamiPF00293. NUDIX. 1 hit.
    [Graphical view]
    SUPFAMiSSF55811. SSF55811. 1 hit.
    PROSITEiPS51462. NUDIX. 1 hit.
    PS00893. NUDIX_BOX. 1 hit.
    [Graphical view]
    ProtoNetiSearch...

    Entry informationi

    Entry nameiNUD10_HUMAN
    AccessioniPrimary (citable) accession number: Q8NFP7
    Secondary accession number(s): A8K7D7
    , D3DX69, Q86VK1, Q86VR0
    Entry historyi
    Integrated into UniProtKB/Swiss-Prot: July 5, 2005
    Last sequence update: October 1, 2002
    Last modified: November 30, 2016
    This is version 126 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 X
      Human chromosome X: entries, gene names and cross-references to MIM
    2. MIM cross-references
      Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
    3. PDB cross-references
      Index of Protein Data Bank (PDB) cross-references
    4. 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.