Detailed entry information

Protein Information (annotations from UniProt)

Database IDHIV0002017
UniProt IDQ9NV35
Primary gene name(s)NUDT15
Synonym gene name(s)MTH2
Protein nameNucleotide triphosphate diphosphatase NUDT15
Protein functionMay 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. {ECO:0000269|PubMed:19419956, ECO:0000269|PubMed:22556419, ECO:0000269|PubMed:25108385, ECO:0000269|PubMed:26238318}.
Subcellular locationunknown
ECO codeClick here for more information.
Amino acid sequence
FASTA format: Q9NV35
Gene Ontology
(Biological Process)
Complete annatation
dGTP catabolic process [GO:0006203];
DNA protection [GO:0042262];
exogenous drug catabolic process [GO:0042738];
mitotic cell cycle [GO:0000278];
nucleobase-containing small molecule catabolic process [GO:0034656];
nucleoside phosphate catabolic process [GO:1901292];
purine nucleotide catabolic process [GO:0006195];
regulation of proteasomal protein catabolic process [GO:0061136]
Gene Ontology
(Molecular Function)
Complete annatation
8-oxo-7,8-dihydrodeoxyguanosine triphosphate pyrophosphatase activity [GO:0035539];
8-oxo-7,8-dihydroguanosine triphosphate pyrophosphatase activity [GO:0008413];
metal ion binding [GO:0046872];
nucleoside-diphosphatase activity [GO:0017110]
Gene Ontology
(Cellular Component)
Complete annatation
cytosol [GO:0005829]
Protein-protein interaction120559
Phylogenetic treeQ9NV35
HIV replication factor status Zhou et al., Cell. Host. Microbe., 2008
Brass et al., Science, 2008
Smith et al., J. Immunol, 2010
gene status
Lu et al., J. Virol., 2011
      Folds changes 8h: unknown; Folds changes 16h: unknown; Tested: unknown;
Schoggins JW and Rice CM, Curr. Opin. Virol., 2011
      Targeted viruses: unknown
      Viral life cycle: unknown
      Mechanism related to antiviral activity: unknown
Anti-viral restriction factor Liu et al., Retrovirology, 2011
      unknown (Triplicates)

Gene Expression Profile       top

            Up-regulated;            Down-regulated

For brief introduction to each study, please go to the help page.

Gene expression during HIV latency

(1). Mohammadi et al., PLoS Pathog., 2014

Differentially expressed transcripts (Pairwise) during latency and subsequent viral reactivation using several agents - Primary CD4+ T-cell based model

DMSO: Dimethyl suloxyde (negative control) - 0.0033% final
SAHA: Vorinostat (Histone deacetylase inhibitor) - 0.5 μM
CD3: TCR Stimulation by IL-2+ antiCD3/anti-CD28 antibodies
IL7: Interleukin-7 based stimulation
DISU: Disulfiram (alcohol dehydrogenase inhibitor) - 0.5 μM
AZA: 5-azacytidine (AZA; DNA methylation inhibitor) - 1 μM
Experimental Condition Log2 Fold Change P value Adjusted P value
AZA vs. CD31.238395019532390.0002348068382628240.00102222438597903
AZA vs. DISU0.358503075419920.1635862781802060.747228926355439
AZA vs. IL70.341265628210140.0853590830864220.799914411602978
AZA vs. SAHA-1.658259927117930.0005934520738881680.0144752371550004
DISU vs. CD3-0.8924798767588070.01533470571546770.041403430763919
DISU vs. IL7-0.0260168831639490.9187638802511290.984958181665913
DISU vs. SAHA-2.016088182419854.25096123136681e-050.00198963468068103
DMSO vs. AZA-0.1824163663063670.3002690299728881
DMSO vs. CD3-1.430232065635431.57000227978266e-058.64476766992899e-05
DMSO vs. DISU-0.5420153478514880.02949990746125290.346503199876135
DMSO vs. IL70.5302578772388260.00446623130074730.135123561771727
DMSO vs. SAHA-1.482856193215620.002230512531111620.0315643702876837
HIV vs. Mock in Activation-0.02962399732681640.9621119615001040.999983755607037
HIV vs. Mock in Latency0.02728625223665350.8753959064958840.999834320637052
IL7 vs. CD3-0.888735277173980.006523054842544120.0209463156458601
SAHA vs. CD3-2.922966449755991.29846670637868e-071.32215495034639e-06
SAHA vs. IL7-2.003972282095494.89765656577212e-050.001101899627947
(2). Iglesias-Ussel et al., J. Virol., 2013

Up and Downregulated transcripts during Latency (Latently infected CD4+ T cells vs Uninfected)- Primary CD4+Tcell based model
Log2 Fold Change P Value
unknown unknown

Gene expression during HIV infection and replication

(1). Imbeault et al., PloS Pathog., 2012

Transcriptomic profiling of HIV-1 infected CD4+ T cells - Primary CD4+ T cells
Experiment type Log2 Fold Change P Value Adjusted P Value
Infected vs. Mock unknown unknown unknown
Infected vs. Bystander unknown unknown unknown
(2). Lefebvre et al., J. Virol., 2011

Transcriptome analysis of T-cell line (Sup T1)
Log2 Fold Change unknown
(3). Li et al., J. Immunol., 2013

Lymphatic tissue
Acute Fold Change Acute P Value Asymt Fold Change Asypt P Value AIDS Fold Change AIDS P Value
unknown unknown unknown unknown unknown unknown
(4). Chang et al., MBio., 2011

Transcriptome analysis of T-cell line (Sup T1)

Derived from Sherrill-Mix et al., BMC Retrovirol., 2015 cross validation
Up-regulated (True) FALSE
(5). Sherrill-Mix et al., BMC Retrovirol., 2015

Deep RNA-seq analysis of primary human T cell infected with low passage HIV isolate HIV89.6 - Primary CD4+ T cell based
Test Status Log2 Fold Change P Value
OK 0.523212 0.00493672
(6). Rotger et al., PLoS Pathog., 2010

Genome-wide mRNA expression of CD4+ T cells from HIV-infected patient
(Genes differentially expressed (at adjusted p<0.01) according to the empirical Bayes approach)
Log2 Fold Change P Value
unknown unknown

Proteomic/Transcriptomics studies indicating differentially expressed genes mediated by HIV

(1). Greenwood et al., Elife, 2016

Activated (CD3/CD28) Primary human CD4+ T cells infected with pNL4-3-dE-EGFP. The table shows the complete (unfiltered) TMT (tandem mass tag)-based proteomic time course dataset
6 h 24 h 48 h 72 h RTi
0.996 0.931 0.85 0.82 1.053
(2). Navare et al., Virology, 2012

SUP-T1 cell line
FC-4hpi P-value FC-8hpi P-value FC-20hpi P-value Category
unknown unknown unknown unknown unknown unknown unknown
(3). Hyrcza et al., J. Virolo., 2007

Primary human CD4+ and CD8+ T Cells
Affymetrix Prob ID Fold Change In CD8? Category
unknown unknown unknown unknown

Protein Overview       top

Drug-protein Interaction       (annotations from DrugBank)      top

not found

Protein Secondary Structure       (annotations from PDB)      top

PDB Accession Method Resolution Chain Structure Preview
5BON X-ray 1.8Å A/B/C/D/E/F/G/H=1-164.
5LPG X-ray 1.7Å A/B=1-164.

HIV-1 Interaction       (annotations from NCBI HIV-1 Interaction Database)      top

not found

Metabolic/Signalling Pathway       (annotations from KEGG database)      top

Pathway Accession Number Description
not found