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Details on Person UniProt:P36639-3 NUDT1

Class:IdReferenceIsoform:217453
_chainChangeLogtransit peptide:1-18 added on Fri February 6 2015;chain:19-197 added on Fri February 6 2015;transit peptide:1-18 for 217453 removed on Fri February 25 2022;chain:19-197 for 217453 removed on Fri February 25 2022;chain:1-156 for 217453 added on Fri February 25 2022
_displayNameUniProt:P36639-3 NUDT1
_timestamp2025-05-21 21:16:35
chainchain:1-156
checksumB9FB669FF0ACFF5F
commentFUNCTION Oxidized purine nucleoside triphosphate hydrolase which is a prominent sanitizer of the oxidized nucleotide pool (PubMed:10608900, PubMed:12857738, PubMed:22556419, PubMed:24695224, PubMed:24695225, PubMed:26238318, PubMed:28679043, PubMed:7713500, PubMed:8226881). Catalyzes the hydrolysis of 2-oxo-dATP (2-hydroxy-dATP) into 2-oxo-dAMP (PubMed:10373420). Also has a significant hydrolase activity toward 2-oxo-ATP, 8-oxo-dGTP and 8-oxo-dATP (PubMed:10373420, PubMed:11139615). Through the hydrolysis of oxidized purine nucleoside triphosphates, prevents their incorporation into DNA and the subsequent transversions A:T to C:G and G:C to T:A (PubMed:10373420, PubMed:10608900, PubMed:11756418, PubMed:12857738, PubMed:16607562, PubMed:24695224, PubMed:24695225, PubMed:26999531, PubMed:28035004, PubMed:8226881). Also catalyzes the hydrolysis of methylated purine nucleoside triphosphate preventing their integration into DNA (PubMed:30304478, PubMed:32144205). Through this antimutagenic activity protects cells from oxidative stress (PubMed:10608900, PubMed:12857738, PubMed:24695224, PubMed:24695225, PubMed:30304478, PubMed:32144205, PubMed:7713500, PubMed:8226881).CATALYTIC ACTIVITY 2-oxo-dATP + H2O = 2-oxo-dAMP + diphosphate + H(+)CATALYTIC ACTIVITY 2-oxo-ATP + H2O = 2-oxo-AMP + diphosphate + H(+)CATALYTIC ACTIVITY 8-oxo-dGTP + H2O = 8-oxo-dGMP + diphosphate + H(+)CATALYTIC ACTIVITY 8-oxo-dATP + H2O = 8-oxo-dAMP + diphosphate + H(+)CATALYTIC ACTIVITY O(6)-methyl-dGTP + H2O = O(6)-methyl-dGMP + diphosphate + H(+)CATALYTIC ACTIVITY N(6)-methyl-dATP + H2O = N(6)-methyl-dAMP + diphosphate + H(+)CATALYTIC ACTIVITY N(6)-methyl-ATP + H2O = N(6)-methyl-AMP + diphosphate + H(+)COFACTOR Binds 2 Mg(2+) ion per subunit.ACTIVITY REGULATION Inhibited by 2-oxo-dADP and 8-oxo-dGDP.BIOPHYSICOCHEMICAL PROPERTIES kcat is 13.9 sec(-1) with 2-oxo-dATP as substrate (at 30 degrees Celsius and pH 8.0) (PubMed:10373420). kcat is 4.7 sec(-1) with 2-oxo-dATP as substrate (at 30 degrees Celsius and pH 7.2) (PubMed:10373420). kcat is 4.7 sec(-1) with 2-oxo-ATP as substrate (at 30 degrees Celsius and pH 8.0) (PubMed:11139615). kcat is 12.3 sec(-1) with 8-oxo-dGTP as substrate (at 30 degrees Celsius and pH 8.0) (PubMed:10373420). kcat is 2.1 sec(-1) with 8-oxo-dGTP as substrate (at 30 degrees Celsius and pH 7.2) (PubMed:10373420). kcat is 10.8 sec(-1) with 8-oxo-dATP as substrate (at 30 degrees Celsius and pH 8.0) (PubMed:10373420). kcat is 5.4 sec(-1) with O(6)-methyl-dGTP as substrate (at pH 7.5) (PubMed:32144205). kcat is 2.0 sec(-1) with N(6)-methyl-dATP as substrate (at pH 7.5) (PubMed:32144205). kcat is 8.2 sec(-1) with O(6)-methyl-dGTP as substrate (PubMed:30304478). kcat is 0.3 sec(-1) with O(6)-methyl-GTP as substrate (PubMed:30304478). Shows the best catalytic efficiency for the 2-oxo-dATP substrate (PubMed:10373420, PubMed:11139615). Shows a similar catalytic efficiency for 8-oxo-dGTP and O(6)-methyl-dGTP (PubMed:30304478).SUBUNIT Monomer.INTERACTION Mostly present in cytosol (PubMed:7782328). A minor proportion is mitochondrial (PubMed:7782328). A very small amount of the protein is associated with nuclei (PubMed:7782328).SUBCELLULAR LOCATION Widely expressed with highest expression in thymus, testis, embryo and proliferating blood lymphocytes.DEVELOPMENTAL STAGE In peripheral blood lymphocytes, expressed at much higher levels in proliferating cells than in resting cells.PTM The N-terminus is blocked.POLYMORPHISM 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%.MISCELLANEOUS Contains a predicted transit peptide (1-18) for localization to the mitochondrion.MISCELLANEOUS 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.SIMILARITY Belongs to the Nudix hydrolase family.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).
created[InstanceEdit:217385] Schmidt, EE, 2008-03-27 06:23:53
descriptionrecommendedName: fullName evidence="31"Oxidized purine nucleoside triphosphate hydrolase ecNumber evidence="4 7 8 9 13 17 18"3.6.1.56 alternativeName: 2-hydroxy-dATP diphosphatase alternativeName: 7,8-dihydro-8-oxoguanine triphosphatase alternativeName: 8-oxo-dGTPase alternativeName: fullName evidence="36"Methylated purine nucleoside triphosphate hydrolase ecNumber evidence="23 24"3.6.1.- alternativeName: Nucleoside diphosphate-linked moiety X motif 1 shortName: Nudix motif 1
geneNameNUDT1
MTH1
identifierP36639
isoformParent
isSequenceChangedFALSE
keyword3D-structure
Alternative initiation
Cytoplasm
Direct protein sequencing
Hydrolase
Magnesium
Metal-binding
Mitochondrion
Nucleus
Proteomics identification
Reference proteome
RNA-binding
Transit peptide
modified[InstanceEdit:9836292] Weiser, Joel, 2023-05-25
[InstanceEdit:9852000] Weiser, Joel, 2023-11-03
[InstanceEdit:9917590] Weiser, Joel, 2024-08-09
[InstanceEdit:9926675] Weiser, Joel, 2024-11-03
[InstanceEdit:9939033] Weiser, Joel, 2025-02-21
[InstanceEdit:9948485] Weiser, Joel, 2025-05-21
nameNUDT1
referenceDatabase[ReferenceDatabase:2] UniProt
referenceGene[ReferenceDNASequence:9003951] ENSEMBL:ENSG00000106268 NUDT1 [Homo sapiens]
secondaryIdentifier8ODP_HUMAN
A4D205
Q6LES7
Q6P0Y6
Q7Z7N6
Q8IV95
Q9UBM0
Q9UBM9
sequenceLength156
species[Species:48887] Homo sapiens
variantIdentifierP36639-3
(referenceEntity)[EntityWithAccessionedSequence:2395846] NUDT1 p21 [cytosol] [Homo sapiens]
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No pathways have been reviewed or authored by UniProt:P36639-3 NUDT1 (217453)