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Protein

Diphosphoinositol polyphosphate phosphohydrolase 1

Gene

NUDT3

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) 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

    Complete GO annotation...

    Keywords - Molecular functioni

    Hydrolase

    Keywords - Ligandi

    Magnesium, Metal-binding

    Enzyme and pathway databases

    BioCyciMetaCyc:HS03602-MONOMER.
    ZFISH:HS03602-MONOMER.
    BRENDAi3.6.1.60. 2681.
    ReactomeiR-HSA-1855167. Synthesis of pyrophosphates in the cytosol.
    SABIO-RKO95989.
    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

    HGNCiHGNC:8050. NUDT3.

    Subcellular locationi

    GO - Cellular componenti

    • cytoplasm Source: GO_Central
    • cytosol Source: Reactome
    • extracellular exosome Source: UniProtKB
    • nucleus Source: GO_Central
    Complete GO annotation...

    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. 43 interactors.
    IntActiO95989. 41 interactors.
    MINTiMINT-1412881.
    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
    Contains 1 nudix hydrolase domain.PROSITE-ProRule annotation

    Phylogenomic databases

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

    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, AL355855 Genomic DNA. Translation: CAI19715.1.
    AL355855, Z98036 Genomic DNA. Translation: CAH72222.1.
    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.

    Cross-referencesi

    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, AL355855 Genomic DNA. Translation: CAI19715.1.
    AL355855, Z98036 Genomic DNA. Translation: CAH72222.1.
    CH471081 Genomic DNA. Translation: EAX03781.1.
    BC007727 mRNA. Translation: AAH07727.1.
    CCDSiCCDS4791.1.
    RefSeqiNP_006694.1. NM_006703.3.
    UniGeneiHs.188882.

    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...

    Protein-protein interaction databases

    BioGridi116336. 43 interactors.
    IntActiO95989. 41 interactors.
    MINTiMINT-1412881.
    STRINGi9606.ENSP00000351650.

    PTM databases

    iPTMnetiO95989.
    PhosphoSitePlusiO95989.
    SwissPalmiO95989.

    Polymorphism and mutation databases

    BioMutaiNUDT3.

    Proteomic databases

    EPDiO95989.
    MaxQBiO95989.
    PaxDbiO95989.
    PeptideAtlasiO95989.
    PRIDEiO95989.

    Protocols and materials databases

    DNASUi11165.
    Structural Biology KnowledgebaseSearch...

    Genome annotation databases

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

    Organism-specific databases

    CTDi11165.
    DisGeNETi11165.
    GeneCardsiNUDT3.
    HGNCiHGNC:8050. NUDT3.
    HPAiHPA047027.
    HPA055953.
    MIMi609228. gene.
    neXtProtiNX_O95989.
    OpenTargetsiENSG00000272325.
    PharmGKBiPA31834.
    GenAtlasiSearch...

    Phylogenomic databases

    eggNOGiENOG410ISY6. Eukaryota.
    ENOG4111I7R. LUCA.
    GeneTreeiENSGT00390000012928.
    HOGENOMiHOG000237336.
    HOVERGENiHBG053341.
    InParanoidiO95989.
    KOiK07766.
    OMAiLQESCLT.
    OrthoDBiEOG091G0TH6.
    PhylomeDBiO95989.
    TreeFamiTF106349.

    Enzyme and pathway databases

    BioCyciMetaCyc:HS03602-MONOMER.
    ZFISH:HS03602-MONOMER.
    BRENDAi3.6.1.60. 2681.
    ReactomeiR-HSA-1855167. Synthesis of pyrophosphates in the cytosol.
    SABIO-RKO95989.
    SIGNORiO95989.

    Miscellaneous databases

    ChiTaRSiNUDT3. human.
    EvolutionaryTraceiO95989.
    GeneWikiiNUDT3.
    GenomeRNAii11165.
    PROiO95989.
    SOURCEiSearch...

    Gene expression databases

    BgeeiENSG00000272325.
    CleanExiHS_NUDT3.
    GenevisibleiO95989. 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 nameiNUDT3_HUMAN
    AccessioniPrimary (citable) accession number: O95989
    Secondary accession number(s): B2R8N4
    Entry historyi
    Integrated into UniProtKB/Swiss-Prot: July 5, 2005
    Last sequence update: May 1, 1999
    Last modified: November 2, 2016
    This is version 152 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 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

    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.