NUD15_HUMAN
ID NUD15_HUMAN Reviewed; 164 AA.
AC Q9NV35; A2RUR6; Q32Q27; Q6P2C9;
DT 05-JUL-2005, integrated into UniProtKB/Swiss-Prot.
DT 01-OCT-2000, sequence version 1.
DT 03-AUG-2022, entry version 155.
DE RecName: Full=Nucleotide triphosphate diphosphatase NUDT15 {ECO:0000305};
DE EC=3.6.1.9 {ECO:0000269|PubMed:22556419, ECO:0000269|PubMed:26238318, ECO:0000269|PubMed:26878724};
DE AltName: Full=MutT homolog 2 {ECO:0000303|PubMed:19419956};
DE Short=MTH2 {ECO:0000303|PubMed:19419956};
DE AltName: Full=Nucleoside diphosphate-linked moiety X motif 15 {ECO:0000305};
DE Short=Nudix motif 15 {ECO:0000305};
DE AltName: Full=Nucleoside diphosphate-linked to another moiety X hydrolase 15 {ECO:0000303|PubMed:8810257};
DE Short=Nudix hydrolase 15 {ECO:0000312|HGNC:HGNC:23063};
GN Name=NUDT15 {ECO:0000312|HGNC:HGNC:23063};
GN Synonyms=MTH2 {ECO:0000303|PubMed:19419956};
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Placenta;
RX PubMed=14702039; DOI=10.1038/ng1285;
RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R.,
RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H.,
RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.,
RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K.,
RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H.,
RA Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M.,
RA Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K.,
RA Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T.,
RA Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M.,
RA Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S.,
RA Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H.,
RA Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K.,
RA Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N.,
RA Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S.,
RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O.,
RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H.,
RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B.,
RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y.,
RA Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K.,
RA Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T.,
RA Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T.,
RA Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y.,
RA Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H.,
RA Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y.,
RA Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H.,
RA Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O.,
RA Isogai T., Sugano S.;
RT "Complete sequencing and characterization of 21,243 full-length human
RT cDNAs.";
RL Nat. Genet. 36:40-45(2004).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=15057823; DOI=10.1038/nature02379;
RA Dunham A., Matthews L.H., Burton J., Ashurst J.L., Howe K.L.,
RA Ashcroft K.J., Beare D.M., Burford D.C., Hunt S.E., Griffiths-Jones S.,
RA Jones M.C., Keenan S.J., Oliver K., Scott C.E., Ainscough R., Almeida J.P.,
RA Ambrose K.D., Andrews D.T., Ashwell R.I.S., Babbage A.K., Bagguley C.L.,
RA Bailey J., Bannerjee R., Barlow K.F., Bates K., Beasley H., Bird C.P.,
RA Bray-Allen S., Brown A.J., Brown J.Y., Burrill W., Carder C., Carter N.P.,
RA Chapman J.C., Clamp M.E., Clark S.Y., Clarke G., Clee C.M., Clegg S.C.,
RA Cobley V., Collins J.E., Corby N., Coville G.J., Deloukas P., Dhami P.,
RA Dunham I., Dunn M., Earthrowl M.E., Ellington A.G., Faulkner L.,
RA Frankish A.G., Frankland J., French L., Garner P., Garnett J.,
RA Gilbert J.G.R., Gilson C.J., Ghori J., Grafham D.V., Gribble S.M.,
RA Griffiths C., Hall R.E., Hammond S., Harley J.L., Hart E.A., Heath P.D.,
RA Howden P.J., Huckle E.J., Hunt P.J., Hunt A.R., Johnson C., Johnson D.,
RA Kay M., Kimberley A.M., King A., Laird G.K., Langford C.J., Lawlor S.,
RA Leongamornlert D.A., Lloyd D.M., Lloyd C., Loveland J.E., Lovell J.,
RA Martin S., Mashreghi-Mohammadi M., McLaren S.J., McMurray A., Milne S.,
RA Moore M.J.F., Nickerson T., Palmer S.A., Pearce A.V., Peck A.I., Pelan S.,
RA Phillimore B., Porter K.M., Rice C.M., Searle S., Sehra H.K., Shownkeen R.,
RA Skuce C.D., Smith M., Steward C.A., Sycamore N., Tester J., Thomas D.W.,
RA Tracey A., Tromans A., Tubby B., Wall M., Wallis J.M., West A.P.,
RA Whitehead S.L., Willey D.L., Wilming L., Wray P.W., Wright M.W., Young L.,
RA Coulson A., Durbin R.M., Hubbard T., Sulston J.E., Beck S., Bentley D.R.,
RA Rogers J., Ross M.T.;
RT "The DNA sequence and analysis of human chromosome 13.";
RL Nature 428:522-528(2004).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M.,
RA Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J.,
RA Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S.,
RA Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H.,
RA Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K.,
RA Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D.,
RA Hunkapiller M.W., Myers E.W., Venter J.C.;
RL Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases.
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Lymph;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [5]
RP NOMENCLATURE.
RX PubMed=8810257; DOI=10.1074/jbc.271.41.25059;
RA Bessman M.J., Frick D.N., O'Handley S.F.;
RT "The MutT proteins or 'Nudix' hydrolases, a family of versatile, widely
RT distributed, 'housecleaning' enzymes.";
RL J. Biol. Chem. 271:25059-25062(1996).
RN [6]
RP FUNCTION, AND INTERACTION WITH PCNA.
RX PubMed=19419956; DOI=10.1074/jbc.m109.015289;
RA Yu Y., Cai J.-P., Tu B., Wu L., Zhao Y., Liu X., Li L., McNutt M.A.,
RA Feng J., He Q., Yang Y., Wang H., Sekiguchi M., Zhu W.-G.;
RT "Proliferating cell nuclear antigen is protected from degradation by
RT forming a complex with MutT Homolog2.";
RL J. Biol. Chem. 284:19310-19320(2009).
RN [7]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=21269460; DOI=10.1186/1752-0509-5-17;
RA Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T.,
RA Bennett K.L., Superti-Furga G., Colinge J.;
RT "Initial characterization of the human central proteome.";
RL BMC Syst. Biol. 5:17-17(2011).
RN [8]
RP FUNCTION, AND CATALYTIC ACTIVITY.
RX PubMed=22556419; DOI=10.1074/jbc.m112.363010;
RA Takagi Y., Setoyama D., Ito R., Kamiya H., Yamagata Y., Sekiguchi M.;
RT "Human MTH3 (NUDT18) protein hydrolyzes oxidized forms of guanosine and
RT deoxyguanosine diphosphates: comparison with MTH1 and MTH2.";
RL J. Biol. Chem. 287:21541-21549(2012).
RN [9]
RP POLYMORPHISM, AND VARIANT CYS-139.
RX PubMed=25108385; DOI=10.1038/ng.3060;
RA Yang S.K., Hong M., Baek J., Choi H., Zhao W., Jung Y., Haritunians T.,
RA Ye B.D., Kim K.J., Park S.H., Park S.K., Yang D.H., Dubinsky M., Lee I.,
RA McGovern D.P., Liu J., Song K.;
RT "A common missense variant in NUDT15 confers susceptibility to thiopurine-
RT induced leukopenia.";
RL Nat. Genet. 46:1017-1020(2014).
RN [10]
RP POLYMORPHISM, VARIANTS ILE-18; GLY-VAL-18 INS; CYS-139 AND HIS-139,
RP CHARACTERIZATION OF VARIANTS ILE-18; GLY-VAL-18 INS; CYS-139 AND HIS-139,
RP AND CATALYTIC ACTIVITY.
RX PubMed=26878724; DOI=10.1038/ng.3508;
RA Moriyama T., Nishii R., Perez-Andreu V., Yang W., Klussmann F.A., Zhao X.,
RA Lin T.N., Hoshitsuki K., Nersting J., Kihira K., Hofmann U., Komada Y.,
RA Kato M., McCorkle R., Li L., Koh K., Najera C.R., Kham S.K., Isobe T.,
RA Chen Z., Chiew E.K., Bhojwani D., Jeffries C., Lu Y., Schwab M., Inaba H.,
RA Pui C.H., Relling M.V., Manabe A., Hori H., Schmiegelow K., Yeoh A.E.,
RA Evans W.E., Yang J.J.;
RT "NUDT15 polymorphisms alter thiopurine metabolism and hematopoietic
RT toxicity.";
RL Nat. Genet. 48:367-373(2016).
RN [11]
RP X-RAY CRYSTALLOGRAPHY (1.80 ANGSTROMS), SUBUNIT, CATALYTIC ACTIVITY, AND
RP BIOPHYSICOCHEMICAL PROPERTIES.
RX PubMed=26238318; DOI=10.1038/ncomms8871;
RA Carter M., Jemth A.S., Hagenkort A., Page B.D., Gustafsson R., Griese J.J.,
RA Gad H., Valerie N.C., Desroses M., Bostrom J., Warpman Berglund U.,
RA Helleday T., Stenmark P.;
RT "Crystal structure, biochemical and cellular activities demonstrate
RT separate functions of MTH1 and MTH2.";
RL Nat. Commun. 6:7871-7871(2015).
CC -!- FUNCTION: May catalyze the hydrolysis of nucleoside triphosphates
CC including dGTP, dTTP, dCTP, their oxidized forms like 8-oxo-dGTP and
CC the prodrug thiopurine derivatives 6-thio-dGTP and 6-thio-GTP
CC (PubMed:26238318). Could also catalyze the hydrolysis of some
CC nucleoside diphosphate derivatives (PubMed:22556419, PubMed:26238318).
CC Hydrolyzes oxidized nucleosides triphosphates like 8-oxo-dGTP in vitro,
CC but the specificity and efficiency towards these substrates are low.
CC Therefore, the potential in vivo sanitizing role of this enzyme, that
CC would consist in removing oxidatively damaged forms of nucleosides to
CC prevent their incorporation into DNA, is unclear (PubMed:26238318,
CC PubMed:22556419). Through the hydrolysis of thioguanosine triphosphates
CC may participate in the catabolism of thiopurine drugs (PubMed:26238318,
CC PubMed:25108385). May also have a role in DNA synthesis and cell cycle
CC progression by stabilizing PCNA (PubMed:19419956). Exhibits decapping
CC activity towards dpCoA-capped RNAs in vitro (By similarity).
CC {ECO:0000250|UniProtKB:Q8BG93, ECO:0000269|PubMed:19419956,
CC ECO:0000269|PubMed:22556419, ECO:0000269|PubMed:25108385,
CC ECO:0000269|PubMed:26238318}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=a ribonucleoside 5'-triphosphate + H2O = a ribonucleoside 5'-
CC phosphate + diphosphate + H(+); Xref=Rhea:RHEA:23996,
CC ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:33019,
CC ChEBI:CHEBI:58043, ChEBI:CHEBI:61557; EC=3.6.1.9;
CC Evidence={ECO:0000269|PubMed:26238318};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=a 2'-deoxyribonucleoside 5'-triphosphate + H2O = a 2'-
CC deoxyribonucleoside 5'-phosphate + diphosphate + H(+);
CC Xref=Rhea:RHEA:44644, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378,
CC ChEBI:CHEBI:33019, ChEBI:CHEBI:61560, ChEBI:CHEBI:65317; EC=3.6.1.9;
CC Evidence={ECO:0000269|PubMed:26238318};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=a 5'-end CoA-ribonucleoside in mRNA + H2O = (R)-4'-
CC phosphopantetheine + a 5'-end phospho-adenosine-phospho-
CC ribonucleoside in mRNA + 2 H(+); Xref=Rhea:RHEA:67592, Rhea:RHEA-
CC COMP:15719, Rhea:RHEA-COMP:17276, ChEBI:CHEBI:15377,
CC ChEBI:CHEBI:15378, ChEBI:CHEBI:61723, ChEBI:CHEBI:144051,
CC ChEBI:CHEBI:172371; Evidence={ECO:0000250|UniProtKB:Q8BG93};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:67593;
CC Evidence={ECO:0000250|UniProtKB:Q8BG93};
CC -!- COFACTOR:
CC Name=Mg(2+); Xref=ChEBI:CHEBI:18420;
CC Evidence={ECO:0000250|UniProtKB:Q8BG93};
CC Name=Mn(2+); Xref=ChEBI:CHEBI:29035;
CC Evidence={ECO:0000250|UniProtKB:Q8BG93};
CC Note=Magnesium may be the real cofactor in vivo.
CC {ECO:0000250|UniProtKB:Q8BG93};
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC Kinetic parameters:
CC KM=42 uM for dGTP (at pH 7.5) {ECO:0000269|PubMed:26238318};
CC KM=110 uM for 8-oxo-dGTP (at pH 7.5) {ECO:0000269|PubMed:26238318};
CC Note=Has a 10-fold higher catalytic efficiency toward dGTP compared
CC to 8-oxo-dGTP. {ECO:0000269|PubMed:26238318};
CC -!- SUBUNIT: Homodimer (PubMed:26238318). Interacts with PCNA; interaction
CC is disrupted in response to UV irradiation (PubMed:19419956).
CC {ECO:0000269|PubMed:19419956, ECO:0000269|PubMed:26238318}.
CC -!- INTERACTION:
CC Q9NV35; P60520: GABARAPL2; NbExp=3; IntAct=EBI-3924801, EBI-720116;
CC -!- POLYMORPHISM: Polymorphic NUDT15 variants define the poor metabolism of
CC thiopurines 2 genetic locus (THPM2) [MIM:616903]. Thiopurines are used
CC as immunosuppressants or cytotoxic drugs and are prescribed for a
CC variety of clinical conditions including leukemia, autoimmune disease
CC and organ transplantation. Patients with low NUDT15 activities have an
CC increased risk for toxic effects after receiving standard doses of
CC thiopurine drugs. {ECO:0000269|PubMed:25108385,
CC ECO:0000269|PubMed:26878724}.
CC -!- SIMILARITY: Belongs to the Nudix hydrolase family. {ECO:0000305}.
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DR EMBL; AK001818; BAA91925.1; -; mRNA.
DR EMBL; AL158196; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CH471075; EAX08782.1; -; Genomic_DNA.
DR EMBL; BC064607; AAH64607.1; -; mRNA.
DR EMBL; BC107875; AAI07876.1; -; mRNA.
DR EMBL; BC133015; AAI33016.1; -; mRNA.
DR EMBL; BC133017; AAI33018.1; -; mRNA.
DR CCDS; CCDS9407.1; -.
DR RefSeq; NP_001291674.1; NM_001304745.1.
DR RefSeq; NP_060753.1; NM_018283.3.
DR PDB; 5BON; X-ray; 1.80 A; A/B/C/D/E/F/G/H=1-164.
DR PDB; 5LPG; X-ray; 1.70 A; A/B=1-164.
DR PDB; 6T5J; X-ray; 1.60 A; A/B=1-164.
DR PDB; 7AOM; X-ray; 1.95 A; A/B=1-164.
DR PDB; 7AOP; X-ray; 2.35 A; A=1-164.
DR PDB; 7B63; X-ray; 1.60 A; A/B=1-164.
DR PDB; 7B64; X-ray; 1.50 A; A=1-164.
DR PDB; 7B65; X-ray; 1.60 A; A/B=1-164.
DR PDB; 7B66; X-ray; 1.60 A; A/B/C/D=1-164.
DR PDB; 7B67; X-ray; 1.45 A; A/B=1-164.
DR PDB; 7B7V; X-ray; 1.60 A; A/B=1-164.
DR PDB; 7NR6; X-ray; 1.80 A; A/B=1-164.
DR PDBsum; 5BON; -.
DR PDBsum; 5LPG; -.
DR PDBsum; 6T5J; -.
DR PDBsum; 7AOM; -.
DR PDBsum; 7AOP; -.
DR PDBsum; 7B63; -.
DR PDBsum; 7B64; -.
DR PDBsum; 7B65; -.
DR PDBsum; 7B66; -.
DR PDBsum; 7B67; -.
DR PDBsum; 7B7V; -.
DR PDBsum; 7NR6; -.
DR AlphaFoldDB; Q9NV35; -.
DR SMR; Q9NV35; -.
DR BioGRID; 120559; 10.
DR IntAct; Q9NV35; 6.
DR STRING; 9606.ENSP00000258662; -.
DR BindingDB; Q9NV35; -.
DR ChEMBL; CHEMBL4105827; -.
DR DrugBank; DB00993; Azathioprine.
DR iPTMnet; Q9NV35; -.
DR PhosphoSitePlus; Q9NV35; -.
DR BioMuta; NUDT15; -.
DR DMDM; 68565944; -.
DR EPD; Q9NV35; -.
DR jPOST; Q9NV35; -.
DR MassIVE; Q9NV35; -.
DR MaxQB; Q9NV35; -.
DR PaxDb; Q9NV35; -.
DR PeptideAtlas; Q9NV35; -.
DR PRIDE; Q9NV35; -.
DR ProteomicsDB; 82743; -.
DR Antibodypedia; 49562; 166 antibodies from 22 providers.
DR DNASU; 55270; -.
DR Ensembl; ENST00000258662.3; ENSP00000258662.1; ENSG00000136159.4.
DR GeneID; 55270; -.
DR KEGG; hsa:55270; -.
DR MANE-Select; ENST00000258662.3; ENSP00000258662.1; NM_018283.4; NP_060753.1.
DR UCSC; uc001vbw.2; human.
DR CTD; 55270; -.
DR DisGeNET; 55270; -.
DR GeneCards; NUDT15; -.
DR HGNC; HGNC:23063; NUDT15.
DR HPA; ENSG00000136159; Low tissue specificity.
DR MalaCards; NUDT15; -.
DR MIM; 615792; gene.
DR MIM; 616903; phenotype.
DR neXtProt; NX_Q9NV35; -.
DR OpenTargets; ENSG00000136159; -.
DR Orphanet; 99860; Precursor B-cell acute lymphoblastic leukemia.
DR Orphanet; 99861; Precursor T-cell acute lymphoblastic leukemia.
DR Orphanet; 284113; Prediction of susceptibility to adverse reaction due to mercaptopurine.
DR Orphanet; 413687; Prediction of toxicity or dose selection of azathioprine or 6-mercatopurine.
DR PharmGKB; PA134963132; -.
DR VEuPathDB; HostDB:ENSG00000136159; -.
DR eggNOG; ENOG502RXHF; Eukaryota.
DR GeneTree; ENSGT00390000003338; -.
DR HOGENOM; CLU_037162_9_2_1; -.
DR InParanoid; Q9NV35; -.
DR OMA; HFEASRN; -.
DR OrthoDB; 1602447at2759; -.
DR PhylomeDB; Q9NV35; -.
DR TreeFam; TF106353; -.
DR PathwayCommons; Q9NV35; -.
DR Reactome; R-HSA-2393930; Phosphate bond hydrolysis by NUDT proteins.
DR Reactome; R-HSA-9748787; Azathioprine ADME.
DR SABIO-RK; Q9NV35; -.
DR SignaLink; Q9NV35; -.
DR BioGRID-ORCS; 55270; 16 hits in 1078 CRISPR screens.
DR ChiTaRS; NUDT15; human.
DR GenomeRNAi; 55270; -.
DR Pharos; Q9NV35; Tbio.
DR PRO; PR:Q9NV35; -.
DR Proteomes; UP000005640; Chromosome 13.
DR RNAct; Q9NV35; protein.
DR Bgee; ENSG00000136159; Expressed in endothelial cell and 181 other tissues.
DR Genevisible; Q9NV35; HS.
DR GO; GO:0005829; C:cytosol; IBA:GO_Central.
DR GO; GO:0035539; F:8-oxo-7,8-dihydrodeoxyguanosine triphosphate pyrophosphatase activity; IDA:UniProtKB.
DR GO; GO:0008413; F:8-oxo-7,8-dihydroguanosine triphosphate pyrophosphatase activity; IDA:UniProtKB.
DR GO; GO:0044715; F:8-oxo-dGDP phosphatase activity; EXP:Reactome.
DR GO; GO:0036218; F:dTTP diphosphatase activity; IEA:UniProtKB-EC.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0035529; F:NADH pyrophosphatase activity; IEA:UniProtKB-EC.
DR GO; GO:0047429; F:nucleoside-triphosphate diphosphatase activity; IDA:UniProtKB.
DR GO; GO:0006203; P:dGTP catabolic process; IDA:UniProtKB.
DR GO; GO:0042262; P:DNA protection; IMP:UniProtKB.
DR GO; GO:0000278; P:mitotic cell cycle; IMP:UniProtKB.
DR GO; GO:0055086; P:nucleobase-containing small molecule metabolic process; TAS:Reactome.
DR GO; GO:1901292; P:nucleoside phosphate catabolic process; IDA:UniProtKB.
DR GO; GO:0006195; P:purine nucleotide catabolic process; IMP:UniProtKB.
DR GO; GO:0061136; P:regulation of proteasomal protein catabolic process; IMP:UniProtKB.
DR GO; GO:0000302; P:response to reactive oxygen species; IEA:Ensembl.
DR GO; GO:0042178; P:xenobiotic catabolic process; IMP:UniProtKB.
DR InterPro; IPR015797; NUDIX_hydrolase-like_dom_sf.
DR InterPro; IPR000086; NUDIX_hydrolase_dom.
DR Pfam; PF00293; NUDIX; 1.
DR SUPFAM; SSF55811; SSF55811; 1.
DR PROSITE; PS51462; NUDIX; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Hydrolase; Magnesium; Manganese; Metal-binding;
KW Reference proteome.
FT CHAIN 1..164
FT /note="Nucleotide triphosphate diphosphatase NUDT15"
FT /id="PRO_0000057115"
FT DOMAIN 9..145
FT /note="Nudix hydrolase"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00794"
FT REGION 76..164
FT /note="Interaction with PCNA"
FT /evidence="ECO:0000269|PubMed:19419956"
FT MOTIF 48..69
FT /note="Nudix box"
FT BINDING 63
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /evidence="ECO:0000250"
FT BINDING 67
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /evidence="ECO:0000250"
FT VARIANT 18
FT /note="V -> I (associated with increased risk for
FT thiopurines toxicity; decreased thermostability; decreased
FT diphosphatase activity towards 6-thio-dGTP and 6-thio-GTP;
FT dbSNP:rs186364861)"
FT /evidence="ECO:0000269|PubMed:26878724"
FT /id="VAR_076806"
FT VARIANT 18
FT /note="V -> VGV (associated with increased risk for
FT thiopurines toxicity; decreased thermostability; decreased
FT diphosphatase activity towards 6-thio-dGTP and 6-thio-GTP)"
FT /evidence="ECO:0000269|PubMed:26878724"
FT /id="VAR_076807"
FT VARIANT 139
FT /note="R -> C (associated with increased risk for
FT thiopurines toxicity; decreased thermostability; loss of
FT diphosphatase activity towards 6-thio-dGTP and 6-thio-GTP;
FT dbSNP:rs116855232)"
FT /evidence="ECO:0000269|PubMed:25108385,
FT ECO:0000269|PubMed:26878724"
FT /id="VAR_076808"
FT VARIANT 139
FT /note="R -> H (associated with increased risk for
FT thiopurines toxicity; decreased thermostability; decreased
FT diphosphatase activity towards 6-thio-dGTP and 6-thio-GTP;
FT dbSNP:rs147390019)"
FT /evidence="ECO:0000269|PubMed:26878724"
FT /id="VAR_076809"
FT HELIX 8..10
FT /evidence="ECO:0007829|PDB:7B66"
FT STRAND 15..21
FT /evidence="ECO:0007829|PDB:7B67"
FT STRAND 28..34
FT /evidence="ECO:0007829|PDB:7B67"
FT TURN 38..41
FT /evidence="ECO:0007829|PDB:7B67"
FT STRAND 42..44
FT /evidence="ECO:0007829|PDB:5LPG"
FT STRAND 46..49
FT /evidence="ECO:0007829|PDB:7B67"
FT HELIX 56..68
FT /evidence="ECO:0007829|PDB:7B67"
FT STRAND 72..85
FT /evidence="ECO:0007829|PDB:7B67"
FT HELIX 86..88
FT /evidence="ECO:0007829|PDB:7B67"
FT STRAND 90..101
FT /evidence="ECO:0007829|PDB:7B67"
FT TURN 114..116
FT /evidence="ECO:0007829|PDB:7B67"
FT STRAND 117..124
FT /evidence="ECO:0007829|PDB:7B67"
FT HELIX 125..127
FT /evidence="ECO:0007829|PDB:7B67"
FT HELIX 131..133
FT /evidence="ECO:0007829|PDB:7B67"
FT HELIX 136..143
FT /evidence="ECO:0007829|PDB:7B67"
FT HELIX 154..156
FT /evidence="ECO:0007829|PDB:7B67"
SQ SEQUENCE 164 AA; 18609 MW; 9FF20DA411C9E9C7 CRC64;
MTASAQPRGR RPGVGVGVVV TSCKHPRCVL LGKRKGSVGA GSFQLPGGHL EFGETWEECA
QRETWEEAAL HLKNVHFASV VNSFIEKENY HYVTILMKGE VDVTHDSEPK NVEPEKNESW
EWVPWEELPP LDQLFWGLRC LKEQGYDPFK EDLNHLVGYK GNHL
