Skip Header

You are using a version of browser that may not display all the features of this website. Please consider upgrading your browser.
Protein

7,8-dihydro-8-oxoguanine triphosphatase

Gene

NUDT1

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

Functioni

Antimutagenic (PubMed:8226881, PubMed:7713500, PubMed:10608900). Plays a redundant role in sanitizing oxidized nucleotide pools, such as 8-oxo-dGTP pools (PubMed:28679043). Acts as a sanitizing enzyme for oxidized nucleotide pools, thus suppressing cell dysfunction and death induced by oxidative stress (PubMed:12857738, PubMed:24695224, PubMed:24695225). Hydrolyzes 8-oxo-dGTP, 8-oxo-dATP and 2-OH-dATP, thus preventing misincorporation of oxidized purine nucleoside triphosphates into DNA and subsequently preventing A:T to C:G and G:C to T:A transversions (PubMed:8226881, PubMed:10373420, PubMed:10608900, PubMed:11756418, PubMed:12857738, PubMed:16607562, PubMed:24695224, PubMed:24695225, PubMed:26999531, PubMed:28035004). Able to hydrolyze also the corresponding ribonucleotides, 2-OH-ATP, 8-oxo-GTP and 8-oxo-ATP (PubMed:10373420, PubMed:11139615). Does not play a role in U8 snoRNA decapping activity. Binds U8 snoRNA (By similarity).By similarity14 Publications

Caution

The role in cancer cell survival is under debate. Was originally considered to play a role as a sanitizing enzyme for oxidized nucleotide pools, and thus important for the survival of cancer cells (PubMed:24695224, PubMed:24695225). A later study indicates that NUDT1 plays a redundant role in eliminating oxidized nucleotides and that it is not essential for cancer cell proliferation and survival (PubMed:28679043).3 Publications

Catalytic activityi

8-oxo-dGTP + H2O = 8-oxo-dGMP + diphosphate.14 Publications
2-hydroxy-dATP + H2O = 2-hydroxy-dAMP + diphosphate.9 Publications

Cofactori

Mg2+1 PublicationNote: Binds 1 Mg2+ ion per subunit.1 Publication

Enzyme regulationi

2-hydroxy-dATPase activity is inhibited by 2-OH-dADP, 8-OH-dGDP and 8-OH-dGTP. 8-OH-dGTPase activity is inhibited by 8-OH-dGDP, 2-OH-dADP and 2-OH-dATP.1 Publication

Kineticsi

The kinetic constants are determined for the recombinant enzyme expressed in E.coli. 2-hydroxy-rATP shows the best catalytic efficiency.
  1. KM=8.3 µM for 2-hydroxy-dATP (at 30 degrees Celsius and pH 8.0)1 Publication
  2. KM=5.7 µM for 2-hydroxy-dATP (at 30 degrees Celsius and pH 7.2)1 Publication
  3. KM=4.3 µM for 2-hydroxy-rATP (at 30 degrees Celsius and pH 8.0)1 Publication
  4. KM=13.9 µM for 8-hydroxy-dATP (at 30 degrees Celsius and pH 8.0)1 Publication
  5. KM=51.0 µM for 8-hydroxy-rATP (at 30 degrees Celsius and pH 8.0)1 Publication
  6. KM=15.2 µM for 8-hydroxy-dGTP (at 30 degrees Celsius and pH 8.0)1 Publication
  7. KM=12.8 µM for 8-hydroxy-dGTP (at 30 degrees Celsius and pH 7.2)1 Publication
  8. KM=13.2 µM for 8-hydroxy-dGTP (at 22 degrees Celsius and pH 7.5)1 Publication
  9. KM=55.0 µM for 8-hydroxy-rGTP (at 30 degrees Celsius and pH 8.0)1 Publication
  10. KM=258 µM for dGTP (at 30 degrees Celsius and pH 8.0)1 Publication

    pH dependencei

    Optimum pH is 7.8-8.2 with 8-hydroxy-dGTP as substrate, and 8.0-8.5 with 2-hydroxy-dATP as substrate.3 Publications

    Sites

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Binding sitei49Substrate; via carbonyl oxygenCombined sources2 Publications1
    Binding sitei64SubstrateCombined sources2 Publications1
    Sitei68Important for 2-OH-dATPase and 8-oxo-dGTPase activities1 Publication1
    Binding sitei74SubstrateCombined sources2 Publications1
    Metal bindingi78Magnesium; via carbonyl oxygenBy similarity1
    Metal bindingi93MagnesiumBy similarity1
    Metal bindingi96MagnesiumBy similarity1
    Metal bindingi97MagnesiumBy similarity1
    Sitei158Essential for 2-OH-dATPase and 8-oxo-dGTPase activities1 Publication1
    Sitei160Essential for 2-OH-dATPase activity and important for 8-oxo-dGTPase activity1 Publication1

    GO - Molecular functioni

    GO - Biological processi

    • aging Source: Ensembl
    • dATP catabolic process Source: UniProtKB
    • dGTP catabolic process Source: UniProtKB
    • DNA protection Source: UniProtKB
    • DNA repair Source: UniProtKB
    • male gonad development Source: Ensembl
    • nucleobase-containing small molecule catabolic process Source: Reactome
    • purine nucleotide catabolic process Source: UniProtKB
    • response to cadmium ion Source: Ensembl
    • response to oxidative stress Source: ProtInc

    Keywordsi

    Molecular functionHydrolase, RNA-binding
    LigandMagnesium, Metal-binding

    Enzyme and pathway databases

    BioCyciMetaCyc:HS02879-MONOMER
    BRENDAi3.6.1.55 2681
    3.6.1.56 2681
    ReactomeiR-HSA-2393930 Phosphate bond hydrolysis by NUDT proteins
    SABIO-RKiP36639

    Names & Taxonomyi

    Protein namesi
    Recommended name:
    7,8-dihydro-8-oxoguanine triphosphatase (EC:3.6.1.557 Publications)
    Alternative name(s):
    2-hydroxy-dATP diphosphatase (EC:3.6.1.565 Publications)
    8-oxo-dGTPase
    Nucleoside diphosphate-linked moiety X motif 1
    Short name:
    Nudix motif 1
    Gene namesi
    Name:NUDT1
    Synonyms:MTH11 Publication
    OrganismiHomo sapiens (Human)
    Taxonomic identifieri9606 [NCBI]
    Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
    Proteomesi
    • UP000005640 Componenti: Chromosome 7

    Organism-specific databases

    EuPathDBiHostDB:ENSG00000106268.15
    HGNCiHGNC:8048 NUDT1
    MIMi600312 gene
    neXtProtiNX_P36639

    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, Mitochondrion, Nucleus

    Pathology & Biotechi

    Mutagenesis

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Mutagenesisi68F → A: Reduces 2-OH-dATPase and 8-oxo-dGTPase activities. 1 Publication1
    Mutagenesisi77G → R: Reduces activity by 97%. 1 Publication1
    Mutagenesisi78G → F: Loss of activity. 1 Publication1
    Mutagenesisi80V → E: Loss of activity. 1 Publication1
    Mutagenesisi81Q → P: Reduces activity by 97%. 1 Publication1
    Mutagenesisi83G → I: Reduces activity by 60%. 1 Publication1
    Mutagenesisi86I → K: Loss of activity. 1 Publication1
    Mutagenesisi88D → P: Loss of activity. 1 Publication1
    Mutagenesisi89G → M: Loss of activity. 1 Publication1
    Mutagenesisi90A → P: Loss of activity. 1 Publication1
    Mutagenesisi94L → P: Loss of activity. 1 Publication1
    Mutagenesisi95Q → P: Loss of activity. 1 Publication1
    Mutagenesisi96E → G: Loss of activity. 1 Publication1
    Mutagenesisi97E → A: Loss of ability to prevent DNA damage. Expected to cause loss of enzyme activity. 1 Publication1
    Mutagenesisi97E → Y: Loss of activity. 1 Publication1
    Mutagenesisi98S → R: Loss of activity. 1 Publication1
    Mutagenesisi158W → A: Greatly reduces or abolishes 2-OH-dATPase and 8-oxo-dGTPase activities. 1 Publication1
    Mutagenesisi158W → Y: Enhances 2-OH-dATPase activity and greatly reduces 8-oxo-dGTPase activity. 1 Publication1
    Mutagenesisi160D → A or N: Loss of 2-OH-dATPase activity, reduces 8-oxo-dGTPase activity. 1 Publication1
    Mutagenesisi161D → A or N: Mildly decreased 2-OH-dATPase activity, nearly abolishes 8-oxo-dGTPase activity. 1 Publication1
    Mutagenesisi191L → A: Reduces 2-OH-dATPase and 8-oxo-dGTPase activities and increases thermolability. 1 Publication1
    Mutagenesisi192 – 197Missing : Almost abolishes 2-OH-dATPase and 8-oxo-dGTPase activities and increases thermolability. 1 Publication6
    Mutagenesisi192R → A: Reduces 2-OH-dATPase and 8-oxo-dGTPase activities and increases thermolability. 1 Publication1
    Mutagenesisi193 – 197Missing : Greatly reduces 2-OH-dATPase and 8-oxo-dGTPase activities and increases thermolability. 1 Publication5
    Mutagenesisi193E → A: Reduces 2-OH-dATPase and 8-oxo-dGTPase activities and increases thermolability. 1 Publication1
    Mutagenesisi194 – 197Missing : Reduces 2-OH-dATPase and 8-oxo-dGTPase activities and increases thermolability. 1 Publication4
    Mutagenesisi194V → A: Reduces 2-OH-dATPase and 8-oxo-dGTPase activities and increases thermolability. 1 Publication1
    Mutagenesisi195 – 197Missing : Slightly enhances 2-OH-dATPase and 8-oxo-dGTPase activities and increases thermolability. 1 Publication3
    Mutagenesisi195D → A: Enhances 2-OH-dATPase and 8-oxo-dGTPase activities and increases thermolability. 1 Publication1
    Mutagenesisi196T → A: Reduces 2-OH-dATPase and 8-oxo-dGTPase activities and increases thermolability. 1 Publication1
    Mutagenesisi197V → A: Slightly reduces 2-OH-dATPase and 8-oxo-dGTPase activities and increases thermolability. 1 Publication1

    Organism-specific databases

    DisGeNETi4521
    OpenTargetsiENSG00000106268
    PharmGKBiPA31830

    Chemistry databases

    ChEMBLiCHEMBL3708265

    Polymorphism and mutation databases

    DMDMi254763430

    PTM / Processingi

    Molecule processing

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Transit peptidei1 – 18MitochondrionSequence analysisAdd BLAST18
    ChainiPRO_000001994419 – 1977,8-dihydro-8-oxoguanine triphosphataseAdd BLAST179

    Post-translational modificationi

    The N-terminus is blocked.

    Proteomic databases

    EPDiP36639
    MaxQBiP36639
    PaxDbiP36639
    PeptideAtlasiP36639
    PRIDEiP36639
    ProteomicsDBi55217
    55218 [P36639-2]
    55219 [P36639-3]
    55220 [P36639-4]
    TopDownProteomicsiP36639-4 [P36639-4]

    PTM databases

    iPTMnetiP36639
    PhosphoSitePlusiP36639

    Expressioni

    Tissue specificityi

    Widely expressed with highest expression in thymus, testis, embryo and proliferating blood lymphocytes.1 Publication

    Developmental stagei

    In peripheral blood lymphocytes, expressed at much higher levels in proliferating cells than in resting cells.1 Publication

    Gene expression databases

    BgeeiENSG00000106268
    CleanExiHS_NUDT1
    ExpressionAtlasiP36639 baseline and differential
    GenevisibleiP36639 HS

    Organism-specific databases

    HPAiHPA012636

    Interactioni

    Subunit structurei

    Monomer.2 Publications

    Binary interactionsi

    WithEntry#Exp.IntActNotes
    HEL-S-5V9HWA03EBI-1048967,EBI-10207332

    Protein-protein interaction databases

    BioGridi110621, 14 interactors
    IntActiP36639, 11 interactors
    STRINGi9606.ENSP00000339503

    Chemistry databases

    BindingDBiP36639

    Structurei

    Secondary structure

    1197
    Legend: HelixTurnBeta strandPDB Structure known for this area
    Show more details
    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Beta strandi45 – 54Combined sources10
    Beta strandi56 – 64Combined sources9
    Turni68 – 71Combined sources4
    Beta strandi72 – 74Combined sources3
    Beta strandi76 – 79Combined sources4
    Helixi86 – 98Combined sources13
    Beta strandi101 – 103Combined sources3
    Beta strandi105 – 115Combined sources11
    Beta strandi120 – 131Combined sources12
    Beta strandi132 – 134Combined sources3
    Beta strandi140 – 148Combined sources9
    Helixi149 – 151Combined sources3
    Helixi154 – 156Combined sources3
    Helixi161 – 169Combined sources9
    Beta strandi173 – 181Combined sources9
    Turni182 – 184Combined sources3
    Beta strandi185 – 195Combined sources11

    3D structure databases

    ProteinModelPortaliP36639
    SMRiP36639
    ModBaseiSearch...
    MobiDBiSearch...

    Miscellaneous databases

    EvolutionaryTraceiP36639

    Family & Domainsi

    Domains and Repeats

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Domaini44 – 173Nudix hydrolasePROSITE-ProRule annotationAdd BLAST130

    Region

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Regioni76 – 79Substrate bindingCombined sources1 Publication4
    Regioni158 – 161Substrate bindingCombined sources2 Publications4

    Motif

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Motifi78 – 99Nudix boxPROSITE-ProRule annotationAdd BLAST22

    Sequence similaritiesi

    Belongs to the Nudix hydrolase family.Curated

    Keywords - Domaini

    Transit peptide

    Phylogenomic databases

    eggNOGiENOG410IXIA Eukaryota
    COG0494 LUCA
    GeneTreeiENSGT00390000000341
    HOGENOMiHOG000261970
    HOVERGENiHBG000032
    InParanoidiP36639
    KOiK17816
    OMAiGAGKWNG
    OrthoDBiEOG091G0O4Y
    PhylomeDBiP36639
    TreeFamiTF106348

    Family and domain databases

    InterProiView protein in InterPro
    IPR020476 Nudix_hydrolase
    IPR015797 NUDIX_hydrolase-like_dom_sf
    IPR020084 NUDIX_hydrolase_CS
    IPR000086 NUDIX_hydrolase_dom
    IPR003563 OxG-triPHTase
    PfamiView protein in Pfam
    PF00293 NUDIX, 1 hit
    PRINTSiPR01403 8OXTPHPHTASE
    PR00502 NUDIXFAMILY
    SUPFAMiSSF55811 SSF55811, 1 hit
    PROSITEiView protein in PROSITE
    PS51462 NUDIX, 1 hit
    PS00893 NUDIX_BOX, 1 hit

    Sequences (4)i

    Sequence statusi: Complete.

    Sequence processingi: The displayed sequence is further processed into a mature form.

    This entry describes 4 isoformsi produced by alternative initiation. AlignAdd to basket

    Isoform p26 (identifier: P36639-1) [UniParc]FASTAAdd to basket

    This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

    « Hide

            10         20         30         40         50
    MYWSNQITRR LGERVQGFMS GISPQQMGEP EGSWSGKNPG TMGASRLYTL
    60 70 80 90 100
    VLVLQPQRVL LGMKKRGFGA GRWNGFGGKV QEGETIEDGA RRELQEESGL
    110 120 130 140 150
    TVDALHKVGQ IVFEFVGEPE LMDVHVFCTD SIQGTPVESD EMRPCWFQLD
    160 170 180 190
    QIPFKDMWPD DSYWFPLLLQ KKKFHGYFKF QGQDTILDYT LREVDTV
    Note: Derived from a B-type mRNA with a polymorphic alteration (GU-->GC) at the beginning of exon 2c that converts an in-frame UGA to CGA yielding another in-frame AUG further upstream.
    Length:197
    Mass (Da):22,520
    Last modified:July 28, 2009 - v3
    Checksum:i82AFF5E1CE287957
    GO
    Isoform p22 (identifier: P36639-2) [UniParc]FASTAAdd to basket

    The sequence of this isoform differs from the canonical sequence as follows:
         1-18: Missing.

    Show »
    Length:179
    Mass (Da):20,296
    Checksum:i7C9F192384F66C61
    GO
    Isoform p21 (identifier: P36639-3) [UniParc]FASTAAdd to basket

    The sequence of this isoform differs from the canonical sequence as follows:
         1-26: Missing.

    Show »
    Length:171
    Mass (Da):19,467
    Checksum:i06DE501D75A8B3D6
    GO
    Isoform p18 (identifier: P36639-4) [UniParc]FASTAAdd to basket

    The sequence of this isoform differs from the canonical sequence as follows:
         1-41: Missing.

    Show »
    Length:156
    Mass (Da):17,952
    Checksum:iB9FB669FF0ACFF5F
    GO

    Polymorphismi

    A polymorphism between Met-1 and Met-19 removes a stop codon before the initiation codon for isoform p22 and gives rise to the production of isoform p26. The allele frequency of isoform p26 is about 20%.1 Publication

    Natural variant

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Natural variantiVAR_06871577G → W. Corresponds to variant dbSNP:rs11547459Ensembl.1
    Natural variantiVAR_013757124V → M Associated with type I diabetes in Japanese female population; may be associated with an increased risk for small cell lung carcinoma (SCLC); decreased efficiency of translocation to mitochondria. 5 PublicationsCorresponds to variant dbSNP:rs4866Ensembl.1

    Alternative sequence

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Alternative sequenceiVSP_0188141 – 41Missing in isoform p18. 4 PublicationsAdd BLAST41
    Alternative sequenceiVSP_0188131 – 26Missing in isoform p21. CuratedAdd BLAST26
    Alternative sequenceiVSP_0188121 – 18Missing in isoform p22. 1 PublicationAdd BLAST18

    Sequence databases

    Select the link destinations:
    EMBLi
    GenBanki
    DDBJi
    Links Updated
    D16581 mRNA Translation: BAA04013.1
    D38594 Genomic DNA Translation: BAA07601.1
    AB025233 mRNA Translation: BAA83791.1
    AB025234 mRNA Translation: BAA83792.1
    AB025235 mRNA Translation: BAA83793.1
    AB025236 mRNA Translation: BAA83794.1
    AB025237 mRNA Translation: BAA83795.1
    AB025238 mRNA Translation: BAA83796.1
    AB025239 mRNA Translation: BAA83797.1
    AB025240 mRNA Translation: BAA83798.1
    AB025241 mRNA Translation: BAA83799.1
    AB025242 mRNA Translation: BAA83800.1
    DQ230907 Genomic DNA Translation: ABB02181.1
    CH236953 Genomic DNA Translation: EAL23948.1
    CH236953 Genomic DNA Translation: EAL23949.1
    CR407655 mRNA Translation: CAG28583.1
    CH471144 Genomic DNA Translation: EAW87225.1
    CH471144 Genomic DNA Translation: EAW87227.1
    AC004971 Genomic DNA No translation available.
    BC014618 mRNA Translation: AAH14618.1
    BC040144 mRNA Translation: AAH40144.2
    BC051375 mRNA Translation: AAH51375.2
    BC065367 mRNA Translation: AAH65367.1
    CCDSiCCDS5329.1 [P36639-2]
    CCDS5330.1 [P36639-4]
    RefSeqiNP_002443.3, NM_002452.3 [P36639-4]
    NP_945186.1, NM_198948.1 [P36639-4]
    NP_945187.1, NM_198949.1 [P36639-2]
    NP_945188.1, NM_198950.1 [P36639-4]
    NP_945190.1, NM_198952.1 [P36639-2]
    NP_945191.1, NM_198953.1 [P36639-4]
    NP_945192.1, NM_198954.1 [P36639-2]
    UniGeneiHs.534331

    Genome annotation databases

    EnsembliENST00000339737; ENSP00000343439; ENSG00000106268 [P36639-4]
    ENST00000343985; ENSP00000339503; ENSG00000106268 [P36639-2]
    ENST00000356714; ENSP00000349148; ENSG00000106268 [P36639-4]
    ENST00000397046; ENSP00000380239; ENSG00000106268 [P36639-4]
    ENST00000397048; ENSP00000380241; ENSG00000106268 [P36639-2]
    ENST00000397049; ENSP00000380242; ENSG00000106268 [P36639-4]
    GeneIDi4521
    KEGGihsa:4521
    UCSCiuc003slr.1 human [P36639-1]

    Keywords - Coding sequence diversityi

    Alternative initiation, Polymorphism

    Similar proteinsi

    Entry informationi

    Entry namei8ODP_HUMAN
    AccessioniPrimary (citable) accession number: P36639
    Secondary accession number(s): A4D205
    , Q6LES7, Q6P0Y6, Q7Z7N6, Q8IV95, Q9UBM0, Q9UBM9
    Entry historyiIntegrated into UniProtKB/Swiss-Prot: June 1, 1994
    Last sequence update: July 28, 2009
    Last modified: July 18, 2018
    This is version 178 of the entry and version 3 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, Direct protein sequencing, Reference proteome

    Documents

    1. Human chromosome 7
      Human chromosome 7: entries, gene names and cross-references to MIM
    2. Human entries with polymorphisms or disease mutations
      List of human entries with polymorphisms or disease mutations
    3. Human polymorphisms and disease mutations
      Index of human polymorphisms and disease mutations
    4. MIM cross-references
      Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
    5. PDB cross-references
      Index of Protein Data Bank (PDB) cross-references
    6. SIMILARITY comments
      Index of protein domains and families

    We'd like to inform you that we have updated our Privacy Notice to comply with Europe’s new General Data Protection Regulation (GDPR) that applies since 25 May 2018.

    Do not show this banner again
    UniProt is an ELIXIR core data resource
    Main funding by: National Institutes of Health