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Protein

Diphosphoinositol polyphosphate phosphohydrolase 1

Gene

NUDT3

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) and [PP]2-InsP4 (bisdiphosphoinositol tetrakisphosphate), suggesting that it may play a role in signal transduction. InsP6 (inositol hexakisphophate) is not a substrate. Acts as a negative regulator of the ERK1/2 pathway. 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

Cofactori

Mg2+1 PublicationNote: Binds 3 Mg2+ ions per subunit.1 Publication

Enzyme regulationi

Inhibited by fluoride and InsP6.1 Publication

Kineticsi

  1. KM=5.9 µM for Ap6A3 Publications
  2. KM=7.7 µM for Ap5A3 Publications
  3. KM=38 mM for 5-phosphoribose 1-diphosphate3 Publications
  4. KM=4.2 nM for PP-InsP53 Publications

    pH dependencei

    Optimum pH is 7-7.5.3 Publications

    Sites

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Binding sitei10Substrate1
    Binding sitei41Substrate1
    Metal bindingi50Magnesium 1; via carbonyl oxygen1
    Metal bindingi66Magnesium 21
    Metal bindingi66Magnesium 31
    Active sitei69Proton acceptorCurated1
    Metal bindingi70Magnesium 11

    GO - Molecular functioni

    GO - Biological processi

    Keywordsi

    Molecular functionHydrolase
    LigandMagnesium, Metal-binding

    Enzyme and pathway databases

    BioCyciMetaCyc:HS03602-MONOMER
    BRENDAi3.6.1.60 2681
    ReactomeiR-HSA-1855167 Synthesis of pyrophosphates in the cytosol
    SABIO-RKiO95989
    SIGNORiO95989

    Names & Taxonomyi

    Protein namesi
    Recommended name:
    Diphosphoinositol polyphosphate phosphohydrolase 1 (EC:3.6.1.52)
    Short name:
    DIPP-1
    Alternative name(s):
    Diadenosine 5',5'''-P1,P6-hexaphosphate hydrolase 1 (EC:3.6.1.-)
    Nucleoside diphosphate-linked moiety X motif 3
    Short name:
    Nudix motif 3
    Gene namesi
    Name:NUDT3
    Synonyms:DIPP, DIPP1
    OrganismiHomo sapiens (Human)
    Taxonomic identifieri9606 [NCBI]
    Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
    Proteomesi
    • UP000005640 Componenti: Chromosome 6

    Organism-specific databases

    EuPathDBiHostDB:ENSG00000272325.1
    HGNCiHGNC:8050 NUDT3
    MIMi609228 gene
    neXtProtiNX_O95989

    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

    Mutagenesis

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Mutagenesisi50G → A or V: Loss of function. 1 Publication1
    Mutagenesisi51G → A: Loss of function. 1 Publication1
    Mutagenesisi52G → A or V: Loss of function. 1 Publication1
    Mutagenesisi66E → Q: Loss of function. 1 Publication1
    Mutagenesisi70E → Q: Loss of function. 1 Publication1
    Mutagenesisi72G → A: Loss of function. 1 Publication1
    Mutagenesisi75G → A: Loss of function. 1 Publication1
    Mutagenesisi78G → A: No effect. 1 Publication1
    Mutagenesisi78G → V: Loss of function. 1 Publication1
    Mutagenesisi82G → A: Loss of function. 1 Publication1
    Mutagenesisi84F → Y: Induces a strong decrease in Ap6A and [PP]-InsP4 hydrolysis, while it only weakly affects PP-InsP5 hydrolysis. 1 Publication1
    Mutagenesisi91H → L: Induces a strong decrease in Ap6A and [PP]-InsP4 hydrolysis, while it only weakly affects PP-InsP5 hydrolysis. 1 Publication1

    Organism-specific databases

    DisGeNETi11165
    OpenTargetsiENSG00000272325
    PharmGKBiPA31834

    Polymorphism and mutation databases

    BioMutaiNUDT3

    PTM / Processingi

    Molecule processing

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    ChainiPRO_00000570551 – 172Diphosphoinositol polyphosphate phosphohydrolase 1Add BLAST172

    Amino acid modifications

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Modified residuei1N-acetylmethionineCombined sources1

    Keywords - PTMi

    Acetylation

    Proteomic databases

    EPDiO95989
    MaxQBiO95989
    PaxDbiO95989
    PeptideAtlasiO95989
    PRIDEiO95989

    PTM databases

    iPTMnetiO95989
    PhosphoSitePlusiO95989
    SwissPalmiO95989

    Expressioni

    Tissue specificityi

    Widely expressed. Expressed at higher level in brain, heart, pancreas and liver. Also expressed in placenta, lung and kidney.1 Publication

    Gene expression databases

    BgeeiENSG00000272325
    CleanExiHS_NUDT3
    GenevisibleiO95989 HS

    Organism-specific databases

    HPAiHPA047027
    HPA055953

    Interactioni

    Subunit structurei

    Monomer.By similarity

    Protein-protein interaction databases

    BioGridi116336, 45 interactors
    IntActiO95989, 41 interactors
    MINTiO95989
    STRINGi9606.ENSP00000351650

    Structurei

    Secondary structure

    1172
    Legend: HelixTurnBeta strandPDB Structure known for this area
    Show more details
    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Beta strandi18 – 28Combined sources11
    Beta strandi33 – 38Combined sources6
    Beta strandi45 – 47Combined sources3
    Beta strandi49 – 52Combined sources4
    Helixi59 – 71Combined sources13
    Beta strandi73 – 86Combined sources14
    Turni87 – 90Combined sources4
    Beta strandi91 – 103Combined sources13
    Helixi108 – 113Combined sources6
    Beta strandi117 – 121Combined sources5
    Helixi122 – 129Combined sources8
    Turni130 – 132Combined sources3
    Helixi134 – 139Combined sources6

    3D structure databases

    Select the link destinations:
    PDBei
    RCSB PDBi
    PDBji
    Links Updated
    PDB entryMethodResolution (Å)ChainPositionsPDBsum
    2FVVX-ray1.25A1-172[»]
    2Q9PX-ray1.65A1-172[»]
    ProteinModelPortaliO95989
    SMRiO95989
    ModBaseiSearch...
    MobiDBiSearch...

    Miscellaneous databases

    EvolutionaryTraceiO95989

    Family & Domainsi

    Domains and Repeats

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Domaini17 – 142Nudix hydrolasePROSITE-ProRule annotationAdd BLAST126

    Region

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Regioni18 – 20Substrate binding3
    Regioni89 – 91Substrate binding3

    Motif

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Motifi51 – 72Nudix boxAdd BLAST22

    Sequence similaritiesi

    Belongs to the Nudix hydrolase family. DIPP subfamily.Curated

    Phylogenomic databases

    eggNOGiENOG410ISY6 Eukaryota
    ENOG4111I7R LUCA
    GeneTreeiENSGT00390000012928
    HOGENOMiHOG000237336
    HOVERGENiHBG053341
    InParanoidiO95989
    KOiK07766
    OMAiNNGTPVM
    OrthoDBiEOG091G0TH6
    PhylomeDBiO95989
    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.

    O95989-1 [UniParc]FASTAAdd to basket

    « Hide

            10         20         30         40         50
    MMKLKSNQTR TYDGDGYKKR AACLCFRSES EEEVLLVSSS RHPDRWIVPG
    60 70 80 90 100
    GGMEPEEEPS VAAVREVCEE AGVKGTLGRL VGIFENQERK HRTYVYVLIV
    110 120 130 140 150
    TEVLEDWEDS VNIGRKREWF KIEDAIKVLQ YHKPVQASYF ETLRQGYSAN
    160 170
    NGTPVVATTY SVSAQSSMSG IR
    Length:172
    Mass (Da):19,471
    Last modified:May 1, 1999 - v1
    Checksum:iDE823FECF5C6438A
    GO

    Sequence databases

    Select the link destinations:
    EMBLi
    GenBanki
    DDBJi
    Links Updated
    AF062529 mRNA Translation: AAC83224.1
    AF062530 mRNA Translation: AAC83225.1
    BT019984 mRNA Translation: AAV38787.1
    BT019985 mRNA Translation: AAV38788.1
    AK313440 mRNA Translation: BAG36231.1
    Z98036 Genomic DNA No translation available.
    AL355855 Genomic DNA No translation available.
    CH471081 Genomic DNA Translation: EAX03781.1
    BC007727 mRNA Translation: AAH07727.1
    CCDSiCCDS4791.1
    RefSeqiNP_006694.1, NM_006703.3
    UniGeneiHs.188882

    Genome annotation databases

    EnsembliENST00000607016; ENSP00000476119; ENSG00000272325
    GeneIDi11165
    KEGGihsa:11165
    UCSCiuc003ojl.4 human

    Similar proteinsi

    Entry informationi

    Entry nameiNUDT3_HUMAN
    AccessioniPrimary (citable) accession number: O95989
    Secondary accession number(s): B2R8N4
    Entry historyiIntegrated into UniProtKB/Swiss-Prot: July 5, 2005
    Last sequence update: May 1, 1999
    Last modified: May 23, 2018
    This is version 161 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

    Documents

    1. Human chromosome 6
      Human chromosome 6: 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

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