UniProtKB - Q9NV35 (NUD15_HUMAN)
Protein
Nucleotide triphosphate diphosphatase NUDT15
Gene
NUDT15
Organism
Homo sapiens (Human)
Status
Functioni
May catalyze 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:26238318, PubMed:22556419). Through the hydrolysis of thioguanosine triphosphates may participate in the catabolism of thiopurine drugs (PubMed:26238318, PubMed:25108385). May also have a role in DNA synthesis and cell cycle progression by stabilizing PCNA (PubMed:19419956).4 Publications
Catalytic activityi
- a ribonucleoside 5'-triphosphate + H2O = a ribonucleoside 5'-phosphate + diphosphate + H+1 PublicationEC:3.6.1.91 Publication
- a 2'-deoxyribonucleoside 5'-triphosphate + H2O = a 2'-deoxyribonucleoside 5'-phosphate + diphosphate + H+1 PublicationEC:3.6.1.91 Publication
Cofactori
Kineticsi
Has a 10-fold higher catalytic efficiency toward dGTP compared to 8-oxo-dGTP.1 Publication
- KM=42 µM for dGTP (at pH 7.5)1 Publication
- KM=110 µM for 8-oxo-dGTP (at pH 7.5)1 Publication
Sites
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Metal bindingi | 63 | Magnesium or manganeseBy similarity | 1 | |
Metal bindingi | 67 | Magnesium or manganeseBy similarity | 1 |
GO - Molecular functioni
- 8-oxo-7,8-dihydrodeoxyguanosine triphosphate pyrophosphatase activity Source: UniProtKB
- 8-oxo-7,8-dihydroguanosine triphosphate pyrophosphatase activity Source: UniProtKB
- dTTP diphosphatase activity Source: UniProtKB-EC
- metal ion binding Source: UniProtKB-KW
- NADH pyrophosphatase activity Source: UniProtKB-EC
- nucleoside-diphosphatase activity Source: Reactome
- nucleoside-triphosphate diphosphatase activity Source: UniProtKB
GO - Biological processi
- dGTP catabolic process Source: UniProtKB
- DNA protection Source: UniProtKB
- exogenous drug catabolic process Source: UniProtKB
- mitotic cell cycle Source: UniProtKB
- nucleobase-containing small molecule catabolic process Source: Reactome
- nucleoside phosphate catabolic process Source: UniProtKB
- purine nucleotide catabolic process Source: UniProtKB
- regulation of proteasomal protein catabolic process Source: UniProtKB
- response to reactive oxygen species Source: Ensembl
Keywordsi
Molecular function | Hydrolase |
Ligand | Magnesium, Manganese, Metal-binding |
Enzyme and pathway databases
PathwayCommonsi | Q9NV35 |
Reactomei | R-HSA-2393930, Phosphate bond hydrolysis by NUDT proteins |
SABIO-RKi | Q9NV35 |
Names & Taxonomyi
Protein namesi | Recommended name: Nucleotide triphosphate diphosphatase NUDT15Curated (EC:3.6.1.93 Publications)Alternative name(s): MutT homolog 21 Publication Short name: MTH21 Publication Nucleoside diphosphate-linked moiety X motif 15Curated Short name: Nudix motif 15Curated Nucleoside diphosphate-linked to another moiety X hydrolase 151 Publication Short name: Nudix hydrolase 15Imported |
Gene namesi | |
Organismi | Homo sapiens (Human) |
Taxonomic identifieri | 9606 [NCBI] |
Taxonomic lineagei | Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo |
Proteomesi |
|
Organism-specific databases
HGNCi | HGNC:23063, NUDT15 |
MIMi | 615792, gene |
neXtProti | NX_Q9NV35 |
VEuPathDBi | HostDB:ENSG00000136159.3 |
Subcellular locationi
Cytosol
- cytosol Source: GO_Central
Pathology & Biotechi
Organism-specific databases
DisGeNETi | 55270 |
MalaCardsi | NUDT15 |
MIMi | 616903, phenotype |
OpenTargetsi | ENSG00000136159 |
Orphaneti | 413687, Azathioprine or 6-mercatopurine toxicity or dose selection |
PharmGKBi | PA134963132 |
Miscellaneous databases
Pharosi | Q9NV35, Tbio |
Chemistry databases
ChEMBLi | CHEMBL4105827 |
DrugBanki | DB00993, Azathioprine |
Genetic variation databases
BioMutai | NUDT15 |
DMDMi | 68565944 |
PTM / Processingi
Molecule processing
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
ChainiPRO_0000057115 | 1 – 164 | Nucleotide triphosphate diphosphatase NUDT15Add BLAST | 164 |
Proteomic databases
EPDi | Q9NV35 |
jPOSTi | Q9NV35 |
MassIVEi | Q9NV35 |
MaxQBi | Q9NV35 |
PaxDbi | Q9NV35 |
PeptideAtlasi | Q9NV35 |
PRIDEi | Q9NV35 |
ProteomicsDBi | 82743 |
PTM databases
iPTMneti | Q9NV35 |
PhosphoSitePlusi | Q9NV35 |
Expressioni
Gene expression databases
Bgeei | ENSG00000136159, Expressed in female gonad and 220 other tissues |
Genevisiblei | Q9NV35, HS |
Organism-specific databases
HPAi | ENSG00000136159, Low tissue specificity |
Interactioni
Subunit structurei
Binary interactionsi
Q9NV35
With | #Exp. | IntAct |
---|---|---|
GABARAPL2 [P60520] | 3 | EBI-3924801,EBI-720116 |
Protein-protein interaction databases
BioGRIDi | 120559, 8 interactors |
IntActi | Q9NV35, 6 interactors |
STRINGi | 9606.ENSP00000258662 |
Chemistry databases
BindingDBi | Q9NV35 |
Miscellaneous databases
RNActi | Q9NV35, protein |
Structurei
Secondary structure
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details3D structure databases
SMRi | Q9NV35 |
ModBasei | Search... |
PDBe-KBi | Search... |
Family & Domainsi
Domains and Repeats
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Domaini | 9 – 145 | Nudix hydrolasePROSITE-ProRule annotationAdd BLAST | 137 |
Region
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Regioni | 76 – 164 | Interaction with PCNA1 PublicationAdd BLAST | 89 |
Motif
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Motifi | 48 – 69 | Nudix boxAdd BLAST | 22 |
Sequence similaritiesi
Belongs to the Nudix hydrolase family.Curated
Phylogenomic databases
eggNOGi | ENOG502RXHF, Eukaryota |
GeneTreei | ENSGT00390000003338 |
HOGENOMi | CLU_037162_9_2_1 |
InParanoidi | Q9NV35 |
OMAi | HYVTLFV |
OrthoDBi | 1602447at2759 |
PhylomeDBi | Q9NV35 |
TreeFami | TF106353 |
Family and domain databases
InterProi | View protein in InterPro IPR015797, NUDIX_hydrolase-like_dom_sf IPR000086, NUDIX_hydrolase_dom |
Pfami | View protein in Pfam PF00293, NUDIX, 1 hit |
SUPFAMi | SSF55811, SSF55811, 1 hit |
PROSITEi | View protein in PROSITE PS51462, NUDIX, 1 hit |
i Sequence
Sequence statusi: Complete.
Q9NV35-1 [UniParc]FASTAAdd to basket
10 20 30 40 50
MTASAQPRGR RPGVGVGVVV TSCKHPRCVL LGKRKGSVGA GSFQLPGGHL
60 70 80 90 100
EFGETWEECA QRETWEEAAL HLKNVHFASV VNSFIEKENY HYVTILMKGE
110 120 130 140 150
VDVTHDSEPK NVEPEKNESW EWVPWEELPP LDQLFWGLRC LKEQGYDPFK
160
EDLNHLVGYK GNHL
Polymorphismi
Polymorphic NUDT15 variants define the poor metabolism of thiopurines 2 genetic locus (THPM2) [MIMi: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.2 Publications
Natural variant
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Natural variantiVAR_076806 | 18 | V → I Associated with increased risk for thiopurines toxicity; decreased thermostability; decreased diphosphatase activity towards 6-thio-dGTP and 6-thio-GTP. 1 PublicationCorresponds to variant dbSNP:rs186364861EnsemblClinVar. | 1 | |
Natural variantiVAR_076807 | 18 | V → VGV Associated with increased risk for thiopurines toxicity; decreased thermostability; decreased diphosphatase activity towards 6-thio-dGTP and 6-thio-GTP. 1 Publication | 1 | |
Natural variantiVAR_076808 | 139 | R → C Associated with increased risk for thiopurines toxicity; decreased thermostability; loss of diphosphatase activity towards 6-thio-dGTP and 6-thio-GTP. 2 PublicationsCorresponds to variant dbSNP:rs116855232EnsemblClinVar. | 1 | |
Natural variantiVAR_076809 | 139 | R → H Associated with increased risk for thiopurines toxicity; decreased thermostability; decreased diphosphatase activity towards 6-thio-dGTP and 6-thio-GTP. 1 PublicationCorresponds to variant dbSNP:rs147390019EnsemblClinVar. | 1 |
Sequence databases
Select the link destinations: EMBLi GenBanki DDBJi Links Updated | AK001818 mRNA Translation: BAA91925.1 AL158196 Genomic DNA No translation available. CH471075 Genomic DNA Translation: EAX08782.1 BC064607 mRNA Translation: AAH64607.1 BC107875 mRNA Translation: AAI07876.1 BC133015 mRNA Translation: AAI33016.1 BC133017 mRNA Translation: AAI33018.1 |
CCDSi | CCDS9407.1 |
RefSeqi | NP_001291674.1, NM_001304745.1 NP_060753.1, NM_018283.3 |
Genome annotation databases
Ensembli | ENST00000258662; ENSP00000258662; ENSG00000136159 |
GeneIDi | 55270 |
KEGGi | hsa:55270 |
UCSCi | uc001vbw.2, human |
Similar proteinsi
Cross-referencesi
Sequence databases
Select the link destinations: EMBLi GenBanki DDBJi Links Updated | AK001818 mRNA Translation: BAA91925.1 AL158196 Genomic DNA No translation available. CH471075 Genomic DNA Translation: EAX08782.1 BC064607 mRNA Translation: AAH64607.1 BC107875 mRNA Translation: AAI07876.1 BC133015 mRNA Translation: AAI33016.1 BC133017 mRNA Translation: AAI33018.1 |
CCDSi | CCDS9407.1 |
RefSeqi | NP_001291674.1, NM_001304745.1 NP_060753.1, NM_018283.3 |
3D structure databases
Select the link destinations: PDBei RCSB PDBi PDBji Links Updated | PDB entry | Method | Resolution (Å) | Chain | Positions | PDBsum |
5BON | X-ray | 1.80 | A/B/C/D/E/F/G/H | 1-164 | [»] | |
5LPG | X-ray | 1.70 | A/B | 1-164 | [»] | |
6T5J | X-ray | 1.60 | A/B | 1-164 | [»] | |
SMRi | Q9NV35 | |||||
ModBasei | Search... | |||||
PDBe-KBi | Search... |
Protein-protein interaction databases
BioGRIDi | 120559, 8 interactors |
IntActi | Q9NV35, 6 interactors |
STRINGi | 9606.ENSP00000258662 |
Chemistry databases
BindingDBi | Q9NV35 |
ChEMBLi | CHEMBL4105827 |
DrugBanki | DB00993, Azathioprine |
PTM databases
iPTMneti | Q9NV35 |
PhosphoSitePlusi | Q9NV35 |
Genetic variation databases
BioMutai | NUDT15 |
DMDMi | 68565944 |
Proteomic databases
EPDi | Q9NV35 |
jPOSTi | Q9NV35 |
MassIVEi | Q9NV35 |
MaxQBi | Q9NV35 |
PaxDbi | Q9NV35 |
PeptideAtlasi | Q9NV35 |
PRIDEi | Q9NV35 |
ProteomicsDBi | 82743 |
Protocols and materials databases
Antibodypediai | 49562, 141 antibodies |
DNASUi | 55270 |
Genome annotation databases
Ensembli | ENST00000258662; ENSP00000258662; ENSG00000136159 |
GeneIDi | 55270 |
KEGGi | hsa:55270 |
UCSCi | uc001vbw.2, human |
Organism-specific databases
CTDi | 55270 |
DisGeNETi | 55270 |
GeneCardsi | NUDT15 |
HGNCi | HGNC:23063, NUDT15 |
HPAi | ENSG00000136159, Low tissue specificity |
MalaCardsi | NUDT15 |
MIMi | 615792, gene 616903, phenotype |
neXtProti | NX_Q9NV35 |
OpenTargetsi | ENSG00000136159 |
Orphaneti | 413687, Azathioprine or 6-mercatopurine toxicity or dose selection |
PharmGKBi | PA134963132 |
VEuPathDBi | HostDB:ENSG00000136159.3 |
GenAtlasi | Search... |
Phylogenomic databases
eggNOGi | ENOG502RXHF, Eukaryota |
GeneTreei | ENSGT00390000003338 |
HOGENOMi | CLU_037162_9_2_1 |
InParanoidi | Q9NV35 |
OMAi | HYVTLFV |
OrthoDBi | 1602447at2759 |
PhylomeDBi | Q9NV35 |
TreeFami | TF106353 |
Enzyme and pathway databases
PathwayCommonsi | Q9NV35 |
Reactomei | R-HSA-2393930, Phosphate bond hydrolysis by NUDT proteins |
SABIO-RKi | Q9NV35 |
Miscellaneous databases
BioGRID-ORCSi | 55270, 5 hits in 875 CRISPR screens |
ChiTaRSi | NUDT15, human |
GenomeRNAii | 55270 |
Pharosi | Q9NV35, Tbio |
PROi | PR:Q9NV35 |
RNActi | Q9NV35, protein |
SOURCEi | Search... |
Gene expression databases
Bgeei | ENSG00000136159, Expressed in female gonad and 220 other tissues |
Genevisiblei | Q9NV35, HS |
Family and domain databases
InterProi | View protein in InterPro IPR015797, NUDIX_hydrolase-like_dom_sf IPR000086, NUDIX_hydrolase_dom |
Pfami | View protein in Pfam PF00293, NUDIX, 1 hit |
SUPFAMi | SSF55811, SSF55811, 1 hit |
PROSITEi | View protein in PROSITE PS51462, NUDIX, 1 hit |
ProtoNeti | Search... |
MobiDBi | Search... |
Entry informationi
Entry namei | NUD15_HUMAN | |
Accessioni | Q9NV35Primary (citable) accession number: Q9NV35 Secondary accession number(s): A2RUR6, Q32Q27, Q6P2C9 | |
Entry historyi | Integrated into UniProtKB/Swiss-Prot: | July 5, 2005 |
Last sequence update: | October 1, 2000 | |
Last modified: | February 10, 2021 | |
This is version 149 of the entry and version 1 of the sequence. See complete history. | ||
Entry statusi | Reviewed (UniProtKB/Swiss-Prot) | |
Annotation program | Chordata Protein Annotation Program | |
Disclaimer | Any 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, Reference proteomeDocuments
- Human chromosome 13
Human chromosome 13: entries, gene names and cross-references to MIM - Human entries with genetic variants
List of human entries with genetic variants - Human variants curated from literature reports
Index of human variants curated from literature reports - MIM cross-references
Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot - PDB cross-references
Index of Protein Data Bank (PDB) cross-references - SIMILARITY comments
Index of protein domains and families