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Details on Person UniProt:Q9NV35 NUDT15

Class:Id	ReferenceGeneProduct:240712
_chainChangeLog	chain:1-164 added on Fri February 6 2015
_displayName	UniProt:Q9NV35 NUDT15
_timestamp	2026-02-20 21:42:25
chain	chain:1-164
checksum	9FF20DA411C9E9C7
comment	FUNCTION Catalyzes the hydrolysis of nucleoside triphosphates including dGTP, dTTP, dCTP, their oxidized forms like 8-oxo-dGTP and the prodrug thiopurine derivatives 6-thio-dGTP and 6-thio-GTP (PubMed:26238318). Could also catalyze the hydrolysis of some nucleoside diphosphate derivatives (PubMed:22556419, PubMed:26238318). Hydrolyzes oxidized nucleosides triphosphates like 8-oxo-dGTP in vitro, but the specificity and efficiency towards these substrates are low. Therefore, the potential in vivo sanitizing role of this enzyme, that would consist in removing oxidatively damaged forms of nucleosides to prevent their incorporation into DNA, is unclear (PubMed:22556419, PubMed:26238318). Through the hydrolysis of thioguanosine triphosphates may participate in the catabolism of thiopurine drugs (PubMed:25108385, PubMed:26238318). May also have a role in DNA synthesis and cell cycle progression by stabilizing PCNA (PubMed:19419956). Exhibits decapping activity towards dpCoA-capped RNAs in vitro (By similarity). In vitro, it catalyzes the hydrolysis of isoprene pyrophosphates, including (2E)-geranyl diphosphate, isopentenyl diphosphate, (2E,6E)-farnesyl diphosphate and dimethylallyl diphosphate (PubMed:38944687). It may therefore play a role in the control of cellular levels of these metabolites that are essential for multiple cellular processes, including isoprenoids synthesis and protein isoprenylation (Probable).CATALYTIC ACTIVITY a ribonucleoside 5'-triphosphate + H2O = a ribonucleoside 5'-phosphate + diphosphate + H(+)CATALYTIC ACTIVITY a 2'-deoxyribonucleoside 5'-triphosphate + H2O = a 2'-deoxyribonucleoside 5'-phosphate + diphosphate + H(+)CATALYTIC ACTIVITY a 5'-end CoA-ribonucleoside in mRNA + H2O = a 5'-end phospho-adenosine-phospho-ribonucleoside in mRNA + (R)-4'-phosphopantetheine + 2 H(+)CATALYTIC ACTIVITY dGTP + H2O = dGMP + diphosphate + H(+)CATALYTIC ACTIVITY (2E)-geranyl diphosphate + H2O = (2E)-geranyl phosphate + phosphate + H(+)CATALYTIC ACTIVITY (2E,6E)-farnesyl diphosphate + H2O = (2E,6E)-farnesyl phosphate + phosphate + H(+)CATALYTIC ACTIVITY isopentenyl diphosphate + H2O = isopentenyl phosphate + phosphate + H(+)CATALYTIC ACTIVITY dimethylallyl diphosphate + H2O = dimethylallyl phosphate + phosphate + H(+)COFACTOR Magnesium may be the real cofactor in vivo.BIOPHYSICOCHEMICAL PROPERTIES Has a 10-fold higher catalytic efficiency toward dGTP compared to 8-oxo-dGTP. kcat is 0.58 sec(-1) with dGTP as substrate (at pH 8.0 and 22 degrees Celsius) (PubMed:38944687). kcat is 0.72 sec(-1) with (2E)-geranyl diphosphate as substrate (at pH 8.0 and 22 degrees Celsius) (PubMed:38944687). kcat is 0.49 sec(-1) with isopentenyl diphosphate as substrate (at pH 8.0 and 22 degrees Celsius) (PubMed:38944687). kcat is 0.94 sec(-1) with dimethylallyl diphosphate as substrate (at pH 8.0 and 22 degrees Celsius) (PubMed:38944687). kcat is 0.10 sec(-1) with (2E,6E)-farnesyl diphosphate as substrate (at pH 8.0 and 22 degrees Celsius) (PubMed:38944687).SUBUNIT Homodimer (PubMed:26238318, PubMed:38944687). Interacts with PCNA; interaction is disrupted in response to UV irradiation (PubMed:19419956).INTERACTION Polymorphic NUDT15 variants define the poor metabolism of thiopurines 2 genetic locus (THPM2) [MIM:616903]. Thiopurines are used as immunosuppressants or cytotoxic drugs and are prescribed for a variety of clinical conditions including leukemia, autoimmune disease and organ transplantation. Patients with low NUDT15 activities have an increased risk for toxic effects after receiving standard doses of thiopurine drugs.SIMILARITY Belongs to the Nudix hydrolase family.
created	[InstanceEdit:217385] Schmidt, EE, 2008-03-27 06:23:53
description	recommendedName: fullName evidence="11"Nucleotide triphosphate diphosphatase NUDT15 ecNumber evidence="8"3.6.1.68 ecNumber evidence="8"3.6.1.76 ecNumber evidence="4 6 7 8"3.6.1.9 alternativeName: fullName evidence="9"MutT homolog 2 shortName evidence="9"MTH2 alternativeName: fullName evidence="11"Nucleoside diphosphate-linked moiety X motif 15 shortName evidence="11"Nudix motif 15 alternativeName: fullName evidence="10"Nucleoside diphosphate-linked to another moiety X hydrolase 15 shortName evidence="13"Nudix hydrolase 15
geneName	NUDT15 MTH2
identifier	Q9NV35
isSequenceChanged	FALSE
keyword	3D-structure Hydrolase Magnesium Manganese Metal-binding Proteomics identification Reference proteome
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:9983091] Weiser, Joel, 2026-02-20
name	NUDT15
referenceDatabase	[ReferenceDatabase:2] UniProt
referenceGene	[ReferenceDNASequence:8995576] ENSEMBL:ENSG00000136159 NUDT15 [Homo sapiens]
secondaryIdentifier	NUD15_HUMAN A2RUR6 Q32Q27 Q6P2C9
sequenceLength	164
species	[Species:48887] Homo sapiens
(referenceEntity)	[EntityWithAccessionedSequence:2394014] NUDT15 [cytosol] [Homo sapiens]
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No pathways have been reviewed or authored by UniProt:Q9NV35 NUDT15 (240712)