NUD15_MOUSE
ID NUD15_MOUSE Reviewed; 170 AA.
AC Q8BG93;
DT 05-JUL-2005, integrated into UniProtKB/Swiss-Prot.
DT 01-MAR-2003, sequence version 1.
DT 03-AUG-2022, entry version 131.
DE RecName: Full=Nucleotide triphosphate diphosphatase NUDT15 {ECO:0000305};
DE EC=3.6.1.9 {ECO:0000269|PubMed:12767940};
DE AltName: Full=MutT homolog 2 {ECO:0000303|PubMed:12767940};
DE Short=mMTH2 {ECO:0000303|PubMed:12767940};
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:0000250|UniProtKB:Q9NV35};
GN Name=Nudt15 {ECO:0000312|MGI:MGI:2443366};
GN Synonyms=Mth2 {ECO:0000303|PubMed:12767940};
OS Mus musculus (Mouse).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Mus; Mus.
OX NCBI_TaxID=10090;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=C57BL/6J; TISSUE=Aorta, Cerebellum, and Vein;
RX PubMed=16141072; DOI=10.1126/science.1112014;
RA Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N.,
RA Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K.,
RA Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J.,
RA Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R.,
RA Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T.,
RA Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A.,
RA Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B.,
RA Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M.,
RA Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S.,
RA Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E.,
RA Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D.,
RA Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M.,
RA Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H.,
RA Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V.,
RA Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S.,
RA Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H.,
RA Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N.,
RA Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F.,
RA Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G.,
RA Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z.,
RA Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C.,
RA Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y.,
RA Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S.,
RA Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K.,
RA Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R.,
RA van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H.,
RA Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M.,
RA Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C.,
RA Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S.,
RA Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K.,
RA Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M.,
RA Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C.,
RA Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A.,
RA Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y.;
RT "The transcriptional landscape of the mammalian genome.";
RL Science 309:1559-1563(2005).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Kidney;
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 [3]
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 [4]
RP FUNCTION, CATALYTIC ACTIVITY, COFACTOR, AND BIOPHYSICOCHEMICAL PROPERTIES.
RX PubMed=12767940; DOI=10.1016/s0006-291x(03)00864-7;
RA Cai J.-P., Ishibashi T., Takagi Y., Hayakawa H., Sekiguchi M.;
RT "Mouse MTH2 protein which prevents mutations caused by 8-oxoguanine
RT nucleotides.";
RL Biochem. Biophys. Res. Commun. 305:1073-1077(2003).
RN [5]
RP INDUCTION.
RX PubMed=19735921; DOI=10.1016/j.jns.2009.07.027;
RA Zheng J.-D., Hei A.-L., Zuo P.-P., Dong Y.-L., Song X.-N., Takagi Y.,
RA Sekiguchi M., Cai J.-P.;
RT "Age-related alterations in the expression of MTH2 in the hippocampus of
RT the SAMP8 mouse with learning and memory deterioration.";
RL J. Neurol. Sci. 287:188-196(2009).
RN [6]
RP FUNCTION, AND CATALYTIC ACTIVITY.
RX PubMed=32432673; DOI=10.1093/nar/gkaa402;
RA Sharma S., Grudzien-Nogalska E., Hamilton K., Jiao X., Yang J., Tong L.,
RA Kiledjian M.;
RT "Mammalian Nudix proteins cleave nucleotide metabolite caps on RNAs.";
RL Nucleic Acids Res. 48:6788-6798(2020).
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:12767940). Could also catalyze the hydrolysis of some
CC nucleoside diphosphate derivatives (By similarity). Hydrolyzes oxidized
CC nucleosides triphosphates like 8-oxo-dGTP in vitro, but the specificity
CC and efficiency towards these substrates are low. Therefore, the
CC potential in vivo sanitizing role of this enzyme, that would consist in
CC removing oxidatively damaged forms of nucleosides to prevent their
CC incorporation into DNA, is unclear (PubMed:12767940). Through the
CC hydrolysis of thioguanosine triphosphates may participate in the
CC catabolism of thiopurine drugs (By similarity). May also have a role in
CC DNA synthesis and cell cycle progression by stabilizing PCNA (By
CC similarity). Exhibits decapping activity towards dpCoA-capped RNAs in
CC vitro (PubMed:32432673). {ECO:0000250|UniProtKB:Q9NV35,
CC ECO:0000269|PubMed:12767940, ECO:0000269|PubMed:32432673}.
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:12767940};
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:12767940};
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:0000305|PubMed:32432673};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:67593;
CC Evidence={ECO:0000305|PubMed:32432673};
CC -!- COFACTOR:
CC Name=Mg(2+); Xref=ChEBI:CHEBI:18420;
CC Evidence={ECO:0000269|PubMed:12767940};
CC Name=Mn(2+); Xref=ChEBI:CHEBI:29035;
CC Evidence={ECO:0000269|PubMed:12767940};
CC Note=Magnesium may be the real cofactor in vivo.
CC {ECO:0000269|PubMed:12767940};
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC Kinetic parameters:
CC KM=32 uM for 8-oxo-dGTP {ECO:0000269|PubMed:12767940};
CC KM=75 uM for dGTP {ECO:0000269|PubMed:12767940};
CC -!- SUBUNIT: Homodimer. Interacts with PCNA; interaction is disrupted in
CC response to UV irradiation. {ECO:0000250|UniProtKB:Q9NV35}.
CC -!- INDUCTION: Progressive reduction of protein levels after 4 month of age
CC in the hippocampus of SAMP8 mouse, a mouse with early aging syndrome
CC and reduced ability of learning and memory.
CC {ECO:0000269|PubMed:19735921}.
CC -!- MISCELLANEOUS: Has the ability to complement a mutation of mutT in
CC E.coli and thereby completely suppress the increased frequency of
CC spontaneous mutations.
CC -!- SIMILARITY: Belongs to the Nudix hydrolase family. {ECO:0000305}.
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DR EMBL; AK032657; BAC27973.1; -; mRNA.
DR EMBL; AK040749; BAC30692.1; -; mRNA.
DR EMBL; BC060962; AAH60962.1; -; mRNA.
DR CCDS; CCDS27270.1; -.
DR RefSeq; NP_766115.1; NM_172527.2.
DR RefSeq; XP_017171430.1; XM_017315941.1.
DR AlphaFoldDB; Q8BG93; -.
DR SMR; Q8BG93; -.
DR STRING; 10090.ENSMUSP00000039537; -.
DR iPTMnet; Q8BG93; -.
DR PhosphoSitePlus; Q8BG93; -.
DR EPD; Q8BG93; -.
DR MaxQB; Q8BG93; -.
DR PaxDb; Q8BG93; -.
DR PRIDE; Q8BG93; -.
DR ProteomicsDB; 287847; -.
DR Antibodypedia; 49562; 166 antibodies from 22 providers.
DR DNASU; 214254; -.
DR Ensembl; ENSMUST00000043813; ENSMUSP00000039537; ENSMUSG00000033405.
DR GeneID; 214254; -.
DR KEGG; mmu:214254; -.
DR UCSC; uc007upv.1; mouse.
DR CTD; 55270; -.
DR MGI; MGI:2443366; Nudt15.
DR VEuPathDB; HostDB:ENSMUSG00000033405; -.
DR eggNOG; ENOG502RXHF; Eukaryota.
DR GeneTree; ENSGT00390000003338; -.
DR HOGENOM; CLU_037162_9_2_1; -.
DR InParanoid; Q8BG93; -.
DR OMA; HFEASRN; -.
DR OrthoDB; 1602447at2759; -.
DR PhylomeDB; Q8BG93; -.
DR TreeFam; TF106353; -.
DR BRENDA; 3.6.1.56; 3474.
DR Reactome; R-MMU-2393930; Phosphate bond hydrolysis by NUDT proteins.
DR Reactome; R-MMU-9748787; Azathioprine ADME.
DR SABIO-RK; Q8BG93; -.
DR BioGRID-ORCS; 214254; 2 hits in 72 CRISPR screens.
DR PRO; PR:Q8BG93; -.
DR Proteomes; UP000000589; Chromosome 14.
DR RNAct; Q8BG93; protein.
DR Bgee; ENSMUSG00000033405; Expressed in spermatocyte and 128 other tissues.
DR Genevisible; Q8BG93; MM.
DR GO; GO:0005829; C:cytosol; IBA:GO_Central.
DR GO; GO:0035539; F:8-oxo-7,8-dihydrodeoxyguanosine triphosphate pyrophosphatase activity; ISS:UniProtKB.
DR GO; GO:0008413; F:8-oxo-7,8-dihydroguanosine triphosphate pyrophosphatase activity; IDA:MGI.
DR GO; GO:0044715; F:8-oxo-dGDP phosphatase activity; ISO:MGI.
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; ISO:MGI.
DR GO; GO:0006203; P:dGTP catabolic process; ISS:UniProtKB.
DR GO; GO:0042262; P:DNA protection; IEA:Ensembl.
DR GO; GO:0000278; P:mitotic cell cycle; ISS:UniProtKB.
DR GO; GO:1901292; P:nucleoside phosphate catabolic process; ISO:MGI.
DR GO; GO:0009217; P:purine deoxyribonucleoside triphosphate catabolic process; IDA:MGI.
DR GO; GO:0006195; P:purine nucleotide catabolic process; ISS:UniProtKB.
DR GO; GO:0061136; P:regulation of proteasomal protein catabolic process; ISS:UniProtKB.
DR GO; GO:0000302; P:response to reactive oxygen species; IDA:MGI.
DR GO; GO:0042178; P:xenobiotic catabolic process; ISS:UniProtKB.
DR InterPro; IPR020476; Nudix_hydrolase.
DR InterPro; IPR015797; NUDIX_hydrolase-like_dom_sf.
DR InterPro; IPR020084; NUDIX_hydrolase_CS.
DR InterPro; IPR000086; NUDIX_hydrolase_dom.
DR Pfam; PF00293; NUDIX; 1.
DR PRINTS; PR00502; NUDIXFAMILY.
DR SUPFAM; SSF55811; SSF55811; 1.
DR PROSITE; PS51462; NUDIX; 1.
DR PROSITE; PS00893; NUDIX_BOX; 1.
PE 1: Evidence at protein level;
KW Hydrolase; Magnesium; Manganese; Metal-binding; Reference proteome.
FT CHAIN 1..170
FT /note="Nucleotide triphosphate diphosphatase NUDT15"
FT /id="PRO_0000057116"
FT DOMAIN 8..144
FT /note="Nudix hydrolase"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00794"
FT REGION 75..163
FT /note="Interaction with PCNA"
FT /evidence="ECO:0000250"
FT MOTIF 47..68
FT /note="Nudix box"
FT BINDING 62
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /evidence="ECO:0000250"
FT BINDING 66
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /evidence="ECO:0000250"
SQ SEQUENCE 170 AA; 19576 MW; B3D5D5FB79FA9851 CRC64;
MAANAEPRRR PGVGVGVVVL SCEHPRCVLL GKRKGSFGAG SFQLPGGHLE FGETWEECAQ
RETWEEAGLH LKNVCFASVV NSFVEKENYH YVTILMKGEV DMTHDSEPRN MEPEKNESWE
WVPWEEFPPL DQLFWALRCL KEQGYDPFKE DLNHLEGYRG EHLERTTKTP
