8ODP_HUMAN
ID 8ODP_HUMAN Reviewed; 156 AA.
AC P36639; A4D205; Q6LES7; Q6P0Y6; Q7Z7N6; Q8IV95; Q9UBM0; Q9UBM9;
DT 01-JUN-1994, integrated into UniProtKB/Swiss-Prot.
DT 29-SEP-2021, sequence version 4.
DT 03-AUG-2022, entry version 203.
DE RecName: Full=Oxidized purine nucleoside triphosphate hydrolase {ECO:0000305|PubMed:10373420};
DE EC=3.6.1.56 {ECO:0000269|PubMed:10373420, ECO:0000269|PubMed:11139615, ECO:0000269|PubMed:11756418, ECO:0000269|PubMed:12857738, ECO:0000269|PubMed:16607562, ECO:0000269|PubMed:24695224, ECO:0000269|PubMed:24695225};
DE AltName: Full=2-hydroxy-dATP diphosphatase;
DE AltName: Full=7,8-dihydro-8-oxoguanine triphosphatase;
DE AltName: Full=8-oxo-dGTPase;
DE AltName: Full=Methylated purine nucleoside triphosphate hydrolase {ECO:0000305|PubMed:30304478};
DE EC=3.6.1.- {ECO:0000269|PubMed:30304478, ECO:0000269|PubMed:32144205};
DE AltName: Full=Nucleoside diphosphate-linked moiety X motif 1;
DE Short=Nudix motif 1;
GN Name=NUDT1; Synonyms=MTH1 {ECO:0000303|PubMed:7713500};
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 [MRNA] (ISOFORM P18), PARTIAL PROTEIN SEQUENCE,
RP CATALYTIC ACTIVITY, AND FUNCTION.
RX PubMed=8226881; DOI=10.1016/s0021-9258(19)49494-5;
RA Sakumi K., Furuichi M., Tsuzuki T., Kakuma T., Kawabata S., Maki H.,
RA Sekiguchi M.;
RT "Cloning and expression of cDNA for a human enzyme that hydrolyzes 8-oxo-
RT dGTP, a mutagenic substrate for DNA synthesis.";
RL J. Biol. Chem. 268:23524-23530(1993).
RN [2]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND FUNCTION.
RX PubMed=7713500; DOI=10.1006/geno.1994.1657;
RA Furuichi M., Yoshida M.C., Oda H., Tajiri T., Nakabeppu Y., Tsuzuki T.,
RA Sekiguchi M.;
RT "Genomic structure and chromosome location of the human mutT homologue gene
RT MTH1 encoding 8-oxo-dGTPase for prevention of A:T to C:G transversion.";
RL Genomics 24:485-490(1994).
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM P18), TISSUE SPECIFICITY, DEVELOPMENTAL
RP STAGE, AND VARIANT MET-83.
RX PubMed=9211940; DOI=10.1074/jbc.272.28.17843;
RA Oda H., Nakabeppu Y., Furuichi M., Sekiguchi M.;
RT "Regulation of expression of the human MTH1 gene encoding 8-oxo-dGTPase.
RT Alternative splicing of transcription products.";
RL J. Biol. Chem. 272:17843-17850(1997).
RN [4]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS P18/P21/P22/P26), ALTERNATIVE
RP INITIATION, AND POLYMORPHISM.
RX PubMed=10536140; DOI=10.1093/nar/27.22.4335;
RA Oda H., Taketomi A., Maruyama R., Itoh R., Nishioka K., Yakushiji H.,
RA Suzuki T., Sekiguchi M., Nakabeppu Y.;
RT "Multi-forms of human MTH1 polypeptides produced by alternative translation
RT initiation and single nucleotide polymorphism.";
RL Nucleic Acids Res. 27:4335-4343(1999).
RN [5]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RG NIEHS SNPs program;
RL Submitted (OCT-2005) to the EMBL/GenBank/DDBJ databases.
RN [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=12690205; DOI=10.1126/science.1083423;
RA Scherer S.W., Cheung J., MacDonald J.R., Osborne L.R., Nakabayashi K.,
RA Herbrick J.-A., Carson A.R., Parker-Katiraee L., Skaug J., Khaja R.,
RA Zhang J., Hudek A.K., Li M., Haddad M., Duggan G.E., Fernandez B.A.,
RA Kanematsu E., Gentles S., Christopoulos C.C., Choufani S., Kwasnicka D.,
RA Zheng X.H., Lai Z., Nusskern D.R., Zhang Q., Gu Z., Lu F., Zeesman S.,
RA Nowaczyk M.J., Teshima I., Chitayat D., Shuman C., Weksberg R.,
RA Zackai E.H., Grebe T.A., Cox S.R., Kirkpatrick S.J., Rahman N.,
RA Friedman J.M., Heng H.H.Q., Pelicci P.G., Lo-Coco F., Belloni E.,
RA Shaffer L.G., Pober B., Morton C.C., Gusella J.F., Bruns G.A.P., Korf B.R.,
RA Quade B.J., Ligon A.H., Ferguson H., Higgins A.W., Leach N.T.,
RA Herrick S.R., Lemyre E., Farra C.G., Kim H.-G., Summers A.M., Gripp K.W.,
RA Roberts W., Szatmari P., Winsor E.J.T., Grzeschik K.-H., Teebi A.,
RA Minassian B.A., Kere J., Armengol L., Pujana M.A., Estivill X.,
RA Wilson M.D., Koop B.F., Tosi S., Moore G.E., Boright A.P., Zlotorynski E.,
RA Kerem B., Kroisel P.M., Petek E., Oscier D.G., Mould S.J., Doehner H.,
RA Doehner K., Rommens J.M., Vincent J.B., Venter J.C., Li P.W., Mural R.J.,
RA Adams M.D., Tsui L.-C.;
RT "Human chromosome 7: DNA sequence and biology.";
RL Science 300:767-772(2003).
RN [7]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM P18).
RA Ebert L., Schick M., Neubert P., Schatten R., Henze S., Korn B.;
RT "Cloning of human full open reading frames in Gateway(TM) system entry
RT vector (pDONR201).";
RL Submitted (MAY-2004) to the EMBL/GenBank/DDBJ databases.
RN [8]
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 [9]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=12853948; DOI=10.1038/nature01782;
RA Hillier L.W., Fulton R.S., Fulton L.A., Graves T.A., Pepin K.H.,
RA Wagner-McPherson C., Layman D., Maas J., Jaeger S., Walker R., Wylie K.,
RA Sekhon M., Becker M.C., O'Laughlin M.D., Schaller M.E., Fewell G.A.,
RA Delehaunty K.D., Miner T.L., Nash W.E., Cordes M., Du H., Sun H.,
RA Edwards J., Bradshaw-Cordum H., Ali J., Andrews S., Isak A., Vanbrunt A.,
RA Nguyen C., Du F., Lamar B., Courtney L., Kalicki J., Ozersky P.,
RA Bielicki L., Scott K., Holmes A., Harkins R., Harris A., Strong C.M.,
RA Hou S., Tomlinson C., Dauphin-Kohlberg S., Kozlowicz-Reilly A., Leonard S.,
RA Rohlfing T., Rock S.M., Tin-Wollam A.-M., Abbott A., Minx P., Maupin R.,
RA Strowmatt C., Latreille P., Miller N., Johnson D., Murray J.,
RA Woessner J.P., Wendl M.C., Yang S.-P., Schultz B.R., Wallis J.W.,
RA Spieth J., Bieri T.A., Nelson J.O., Berkowicz N., Wohldmann P.E.,
RA Cook L.L., Hickenbotham M.T., Eldred J., Williams D., Bedell J.A.,
RA Mardis E.R., Clifton S.W., Chissoe S.L., Marra M.A., Raymond C., Haugen E.,
RA Gillett W., Zhou Y., James R., Phelps K., Iadanoto S., Bubb K., Simms E.,
RA Levy R., Clendenning J., Kaul R., Kent W.J., Furey T.S., Baertsch R.A.,
RA Brent M.R., Keibler E., Flicek P., Bork P., Suyama M., Bailey J.A.,
RA Portnoy M.E., Torrents D., Chinwalla A.T., Gish W.R., Eddy S.R.,
RA McPherson J.D., Olson M.V., Eichler E.E., Green E.D., Waterston R.H.,
RA Wilson R.K.;
RT "The DNA sequence of human chromosome 7.";
RL Nature 424:157-164(2003).
RN [10]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS P18 AND P22), AND VARIANT
RP MET-83.
RC TISSUE=Bone, Lymph, Mammary gland, and Muscle;
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 [11]
RP SUBCELLULAR LOCATION (ISOFORM P18), AND CATALYTIC ACTIVITY.
RX PubMed=7782328; DOI=10.1074/jbc.270.24.14659;
RA Kang D., Nishida J., Iyama A., Nakabeppu Y., Furuichi M., Fujiwara T.,
RA Sekiguchi M., Takeshige K.;
RT "Intracellular localization of 8-oxo-dGTPase in human cells, with special
RT reference to the role of the enzyme in mitochondria.";
RL J. Biol. Chem. 270:14659-14665(1995).
RN [12]
RP FUNCTION, CATALYTIC ACTIVITY, ACTIVITY REGULATION, BIOPHYSICOCHEMICAL
RP PROPERTIES, AND SUBSTRATE SPECIFICITY.
RX PubMed=10373420; DOI=10.1074/jbc.274.26.18201;
RA Fujikawa K., Kamiya H., Yakushiji H., Fujii Y., Nakabeppu Y., Kasai H.;
RT "The oxidized forms of dATP are substrates for the human MutT homologue,
RT the hMTH1 protein.";
RL J. Biol. Chem. 274:18201-18205(1999).
RN [13]
RP FUNCTION, CATALYTIC ACTIVITY, AND MUTAGENESIS OF GLY-36; GLY-37; VAL-39;
RP GLN-40; GLY-42; ILE-45; ASP-47; GLY-48; ALA-49; LEU-53; GLN-54; GLU-55;
RP GLU-56 AND SER-57.
RX PubMed=10608900; DOI=10.1074/jbc.274.53.38251;
RA Fujii Y., Shimokawa H., Sekiguchi M., Nakabeppu Y.;
RT "Functional significance of the conserved residues for the 23-residue
RT module among MTH1 and MutT family proteins.";
RL J. Biol. Chem. 274:38251-38259(1999).
RN [14]
RP FUNCTION, CATALYTIC ACTIVITY, BIOPHYSICOCHEMICAL PROPERTIES, AND SUBSTRATE
RP SPECIFICITY.
RX PubMed=11139615; DOI=10.1093/nar/29.2.449;
RA Fujikawa K., Kamiya H., Yakushiji H., Nakabeppu Y., Kasai H.;
RT "Human MTH1 protein hydrolyzes the oxidized ribonucleotide, 2-hydroxy-
RT ATP.";
RL Nucleic Acids Res. 29:449-454(2001).
RN [15]
RP FUNCTION, CATALYTIC ACTIVITY, MUTAGENESIS OF PHE-27; TRP-117; ASP-119;
RP LEU-150; ARG-151; GLU-152; VAL-153; ASP-154; THR-155; VAL-156;
RP 151-ARG--VAL-156; 152-GLU--VAL-156; 153-VAL--VAL-156 AND 154-ASP--VAL-156,
RP AND REGION.
RX PubMed=11756418; DOI=10.1074/jbc.m110566200;
RA Sakai Y., Furuichi M., Takahashi M., Mishima M., Iwai S., Shirakawa M.,
RA Nakabeppu Y.;
RT "A molecular basis for the selective recognition of 2-hydroxy-dATP and 8-
RT oxo-dGTP by human MTH1.";
RL J. Biol. Chem. 277:8579-8587(2002).
RN [16]
RP FUNCTION, CATALYTIC ACTIVITY, AND SUBCELLULAR LOCATION (ISOFORM P18).
RX PubMed=12857738; DOI=10.1074/jbc.m306201200;
RA Yoshimura D., Sakumi K., Ohno M., Sakai Y., Furuichi M., Iwai S.,
RA Nakabeppu Y.;
RT "An oxidized purine nucleoside triphosphatase, MTH1, suppresses cell death
RT caused by oxidative stress.";
RL J. Biol. Chem. 278:37965-37973(2003).
RN [17]
RP FUNCTION, CATALYTIC ACTIVITY, SUBCELLULAR LOCATION (ISOFORM P26),
RP ALTERNATIVE SPLICING, AND CHARACTERIZATION OF VARIANT MET-83.
RX PubMed=16607562; DOI=10.1007/s00109-006-0053-5;
RA Sakai Y., Oda H., Yoshimura D., Furuichi M., Kang D., Iwai S., Hara T.,
RA Nakabeppu Y.;
RT "The GT to GC single nucleotide polymorphism at the beginning of an
RT alternative exon 2C of human MTH1 gene confers an amino terminal extension
RT that functions as a mitochondrial targeting signal.";
RL J. Mol. Med. 84:660-670(2006).
RN [18]
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 [19]
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 [20]
RP FUNCTION.
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).
RN [21] {ECO:0007744|PDB:1IRY}
RP STRUCTURE BY NMR, SUBUNIT, AND COFACTOR.
RX PubMed=15133035; DOI=10.1074/jbc.m402393200;
RA Mishima M., Sakai Y., Itoh N., Kamiya H., Furuichi M., Takahashi M.,
RA Yamagata Y., Iwai S., Nakabeppu Y., Shirakawa M.;
RT "Structure of human MTH1, a Nudix family hydrolase that selectively
RT degrades oxidized purine nucleoside triphosphates.";
RL J. Biol. Chem. 279:33806-33815(2004).
RN [22]
RP CRYSTALLIZATION, AND PRELIMINARY X-RAY CRYSTALLOGRAPHY (1.95 ANGSTROMS).
RX PubMed=17142918; DOI=10.1107/s1744309106049529;
RA Nakamura T., Kitaguchi Y., Miyazawa M., Kamiya H., Toma S., Ikemizu S.,
RA Shirakawa M., Nakabeppu Y., Yamagata Y.;
RT "Crystallization and preliminary X-ray analysis of human MTH1 complexed
RT with two oxidized nucleotides, 8-oxo-dGMP and 2-oxo-dATP.";
RL Acta Crystallogr. F 62:1283-1285(2006).
RN [23] {ECO:0007744|PDB:3ZR0, ECO:0007744|PDB:3ZR1}
RP X-RAY CRYSTALLOGRAPHY (1.80 ANGSTROMS) IN COMPLEX WITH 8-OXO-DGMP,
RP CATALYTIC ACTIVITY, AND BIOPHYSICOCHEMICAL PROPERTIES.
RX PubMed=21787772; DOI=10.1016/j.febslet.2011.07.017;
RA Svensson L.M., Jemth A.S., Desroses M., Loseva O., Helleday T., Hogbom M.,
RA Stenmark P.;
RT "Crystal structure of human MTH1 and the 8-oxo-dGMP product complex.";
RL FEBS Lett. 585:2617-2621(2011).
RN [24]
RP X-RAY CRYSTALLOGRAPHY (1.80 ANGSTROMS).
RG Structural genomics consortium (SGC);
RA Tresaugues L., Siponen M.I., Arrowsmith C.H., Berglund H., Bountra C.,
RA Collins R., Edwards A.M., Ekblad T., Flodin S., Flores A., Graslund S.,
RA Hammarstrom M., Johansson I., Karlberg T., Kol S., Kotenyova T.,
RA Kouznetsova E., Moche M., Nyman T., Persson C., Schuler H., Schutz P.,
RA Thorsell A.G., Van Der Berg S., Wahlberg E., Weigelt J., Welin M.,
RA Nordlund P.;
RT "Crystal Structure of Human 8-oxo-dGTPase (MTH1).";
RL Submitted (JAN-2011) to the PDB data bank.
RN [25] {ECO:0007744|PDB:4N1T, ECO:0007744|PDB:4N1U}
RP X-RAY CRYSTALLOGRAPHY (1.60 ANGSTROMS) IN COMPLEX WITH SYNTHETIC
RP INHIBITORS, FUNCTION, CATALYTIC ACTIVITY, AND MUTAGENESIS OF GLU-56.
RX PubMed=24695224; DOI=10.1038/nature13181;
RA Gad H., Koolmeister T., Jemth A.S., Eshtad S., Jacques S.A., Strom C.E.,
RA Svensson L.M., Schultz N., Lundback T., Einarsdottir B.O., Saleh A.,
RA Gokturk C., Baranczewski P., Svensson R., Berntsson R.P., Gustafsson R.,
RA Stromberg K., Sanjiv K., Jacques-Cordonnier M.C., Desroses M.,
RA Gustavsson A.L., Olofsson R., Johansson F., Homan E.J., Loseva O.,
RA Brautigam L., Johansson L., Hoglund A., Hagenkort A., Pham T., Altun M.,
RA Gaugaz F.Z., Vikingsson S., Evers B., Henriksson M., Vallin K.S.,
RA Wallner O.A., Hammarstrom L.G., Wiita E., Almlof I., Kalderen C.,
RA Axelsson H., Djureinovic T., Puigvert J.C., Haggblad M., Jeppsson F.,
RA Martens U., Lundin C., Lundgren B., Granelli I., Jensen A.J., Artursson P.,
RA Nilsson J.A., Stenmark P., Scobie M., Berglund U.W., Helleday T.;
RT "MTH1 inhibition eradicates cancer by preventing sanitation of the dNTP
RT pool.";
RL Nature 508:215-221(2014).
RN [26] {ECO:0007744|PDB:4C9W, ECO:0007744|PDB:4C9X}
RP X-RAY CRYSTALLOGRAPHY (1.20 ANGSTROMS) IN COMPLEX WITH SYNTHETIC
RP INHIBITORS, FUNCTION, AND CATALYTIC ACTIVITY.
RX PubMed=24695225; DOI=10.1038/nature13194;
RA Huber K.V., Salah E., Radic B., Gridling M., Elkins J.M., Stukalov A.,
RA Jemth A.S., Gokturk C., Sanjiv K., Stromberg K., Pham T., Berglund U.W.,
RA Colinge J., Bennett K.L., Loizou J.I., Helleday T., Knapp S.,
RA Superti-Furga G.;
RT "Stereospecific targeting of MTH1 by (S)-crizotinib as an anticancer
RT strategy.";
RL Nature 508:222-227(2014).
RN [27] {ECO:0007744|PDB:5FSI, ECO:0007744|PDB:5FSK, ECO:0007744|PDB:5FSL, ECO:0007744|PDB:5FSM, ECO:0007744|PDB:5FSN, ECO:0007744|PDB:5FSO}
RP X-RAY CRYSTALLOGRAPHY (1.24 ANGSTROMS) IN COMPLEX WITH 8-OXO-DGTP;
RP 8-OXO-ATP AND SUBSTRATE ANALOGS, CATALYTIC ACTIVITY, AND FUNCTION.
RX PubMed=26999531; DOI=10.1371/journal.pone.0151154;
RA Nissink J.W., Bista M., Breed J., Carter N., Embrey K., Read J.,
RA Winter-Holt J.J.;
RT "MTH1 Substrate Recognition--An Example of Specific Promiscuity.";
RL PLoS ONE 11:e0151154-e0151154(2016).
RN [28] {ECO:0007744|PDB:5NHY}
RP X-RAY CRYSTALLOGRAPHY (1.72 ANGSTROMS), AND FUNCTION.
RX PubMed=28679043; DOI=10.1021/acschembio.7b00370;
RA Ellermann M., Eheim A., Rahm F., Viklund J., Guenther J., Andersson M.,
RA Ericsson U., Forsblom R., Ginman T., Lindstrom J., Silvander C.,
RA Tresaugues L., Giese A., Bunse S., Neuhaus R., Weiske J., Quanz M.,
RA Glasauer A., Nowak-Reppel K., Bader B., Irlbacher H., Meyer H.,
RA Queisser N., Bauser M., Haegebarth A., Gorjanacz M.;
RT "Novel Class of Potent and Cellularly Active Inhibitors Devalidates MTH1 as
RT Broad-Spectrum Cancer Target.";
RL ACS Chem. Biol. 12:1986-1992(2017).
RN [29] {ECO:0007744|PDB:5GHI, ECO:0007744|PDB:5GHJ, ECO:0007744|PDB:5GHM, ECO:0007744|PDB:5GHN, ECO:0007744|PDB:5GHO, ECO:0007744|PDB:5GHP, ECO:0007744|PDB:5GHQ, ECO:0007744|PDB:5WS7}
RP X-RAY CRYSTALLOGRAPHY (1.00 ANGSTROMS) IN COMPLEXES WITH 8-OXO-DGTP AND
RP 2-OXO-DATP, CATALYTIC ACTIVITY, FUNCTION, AND MUTAGENESIS OF ASP-120.
RX PubMed=28035004; DOI=10.1074/jbc.m116.749713;
RA Waz S., Nakamura T., Hirata K., Koga-Ogawa Y., Chirifu M., Arimori T.,
RA Tamada T., Ikemizu S., Nakabeppu Y., Yamagata Y.;
RT "Structural and Kinetic Studies of the Human Nudix Hydrolase MTH1 Reveal
RT the Mechanism for Its Broad Substrate Specificity.";
RL J. Biol. Chem. 292:2785-2794(2017).
RN [30] {ECO:0007744|PDB:5OTM}
RP X-RAY CRYSTALLOGRAPHY (1.80 ANGSTROMS) IN COMPLEX WITH O(6)-METHYL-DGMP,
RP FUNCTION, CATALYTIC ACTIVITY, BIOPHYSICOCHEMICAL PROPERTIES, SUBSTRATE
RP SPECIFICITY, AND REGION.
RX PubMed=30304478; DOI=10.1093/nar/gky896;
RA Jemth A.S., Gustafsson R., Braeutigam L., Henriksson L., Vallin K.S.A.,
RA Sarno A., Almloef I., Homan E., Rasti A., Warpman Berglund U., Stenmark P.,
RA Helleday T.;
RT "MutT homologue 1 (MTH1) catalyzes the hydrolysis of mutagenic O6-methyl-
RT dGTP.";
RL Nucleic Acids Res. 46:10888-10904(2018).
RN [31] {ECO:0007744|PDB:6QVO}
RP X-RAY CRYSTALLOGRAPHY (2.45 ANGSTROMS) IN COMPLEX WITH N(6)-METHYL-AMP,
RP FUNCTION, CATALYTIC ACTIVITY, AND BIOPHYSICOCHEMICAL PROPERTIES.
RX PubMed=32144205; DOI=10.1074/jbc.ra120.012636;
RA Scaletti E.R., Vallin K.S., Braeutigam L., Sarno A., Warpman Berglund U.,
RA Helleday T., Stenmark P., Jemth A.S.;
RT "MutT homologue 1 (MTH1) removes N6-methyl-dATP from the dNTP pool.";
RL J. Biol. Chem. 295:4761-4772(2020).
RN [32]
RP VARIANT MET-83.
RX PubMed=15516784; DOI=10.1507/endocrj.51.493;
RA Miyako K., Kohno H., Ihara K., Kuromaru R., Matsuura N., Hara T.;
RT "Association study of human MTH1 gene polymorphisms with type 1 diabetes
RT mellitus.";
RL Endocr. J. 51:493-498(2004).
RN [33]
RP VARIANT MET-83.
RX PubMed=16774934; DOI=10.1093/carcin/bgl095;
RA Kohno T., Sakiyama T., Kunitoh H., Goto K., Nishiwaki Y., Saito D.,
RA Hirose H., Eguchi T., Yanagitani N., Saito R., Sasaki-Matsumura R.,
RA Mimaki S., Toyama K., Yamamoto S., Kuchiba A., Sobue T., Ohta T., Ohki M.,
RA Yokota J.;
RT "Association of polymorphisms in the MTH1 gene with small cell lung
RT carcinoma risk.";
RL Carcinogenesis 27:2448-2454(2006).
CC -!- FUNCTION: Oxidized purine nucleoside triphosphate hydrolase which is a
CC prominent sanitizer of the oxidized nucleotide pool (PubMed:8226881,
CC PubMed:7713500, PubMed:10608900, PubMed:12857738, PubMed:22556419,
CC PubMed:26238318, PubMed:24695224, PubMed:24695225, PubMed:28679043).
CC Catalyzes the hydrolysis of 2-oxo-dATP (2-hydroxy-dATP) into 2-oxo-dAMP
CC (PubMed:10373420). Has also a significant hydrolase activity toward 2-
CC oxo-ATP, 8-oxo-dGTP and 8-oxo-dATP (PubMed:10373420, PubMed:11139615).
CC Through the hydrolysis of oxidized purine nucleoside triphosphates,
CC prevents their incorporation into DNA and the subsequent transversions
CC A:T to C:G and G:C to T:A (PubMed:8226881, PubMed:10373420,
CC PubMed:10608900, PubMed:11756418, PubMed:12857738, PubMed:16607562,
CC PubMed:24695224, PubMed:24695225, PubMed:26999531, PubMed:28035004).
CC Also catalyzes the hydrolysis of methylated purine nucleoside
CC triphosphate preventing their integration into DNA (PubMed:30304478,
CC PubMed:32144205). Through this antimutagenic activity protects cells
CC from oxidative stress (PubMed:8226881, PubMed:7713500, PubMed:10608900,
CC PubMed:12857738, PubMed:24695224, PubMed:24695225, PubMed:30304478,
CC PubMed:32144205). {ECO:0000269|PubMed:10373420,
CC ECO:0000269|PubMed:10608900, ECO:0000269|PubMed:11139615,
CC ECO:0000269|PubMed:11756418, ECO:0000269|PubMed:12857738,
CC ECO:0000269|PubMed:16607562, ECO:0000269|PubMed:22556419,
CC ECO:0000269|PubMed:24695224, ECO:0000269|PubMed:24695225,
CC ECO:0000269|PubMed:26238318, ECO:0000269|PubMed:26999531,
CC ECO:0000269|PubMed:28035004, ECO:0000269|PubMed:28679043,
CC ECO:0000269|PubMed:30304478, ECO:0000269|PubMed:32144205,
CC ECO:0000269|PubMed:7713500, ECO:0000269|PubMed:8226881}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=2-oxo-dATP + H2O = 2-oxo-dAMP + diphosphate + H(+);
CC Xref=Rhea:RHEA:31583, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378,
CC ChEBI:CHEBI:33019, ChEBI:CHEBI:63212, ChEBI:CHEBI:77897; EC=3.6.1.56;
CC Evidence={ECO:0000269|PubMed:10373420, ECO:0000269|PubMed:10608900,
CC ECO:0000269|PubMed:11139615, ECO:0000269|PubMed:11756418,
CC ECO:0000269|PubMed:12857738, ECO:0000269|PubMed:16607562,
CC ECO:0000269|PubMed:21787772, ECO:0000269|PubMed:22556419,
CC ECO:0000269|PubMed:24695224, ECO:0000269|PubMed:24695225,
CC ECO:0000269|PubMed:26999531, ECO:0000269|PubMed:28035004,
CC ECO:0000269|PubMed:30304478, ECO:0000269|PubMed:7782328,
CC ECO:0000269|PubMed:8226881};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:31584;
CC Evidence={ECO:0000305|PubMed:10373420};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=2-oxo-ATP + H2O = 2-oxo-AMP + diphosphate + H(+);
CC Xref=Rhea:RHEA:67392, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378,
CC ChEBI:CHEBI:33019, ChEBI:CHEBI:71395, ChEBI:CHEBI:172878;
CC Evidence={ECO:0000269|PubMed:11139615};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:67393;
CC Evidence={ECO:0000305|PubMed:11139615};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=8-oxo-dGTP + H2O = 8-oxo-dGMP + diphosphate + H(+);
CC Xref=Rhea:RHEA:31575, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378,
CC ChEBI:CHEBI:33019, ChEBI:CHEBI:63224, ChEBI:CHEBI:77896;
CC Evidence={ECO:0000269|PubMed:10373420, ECO:0000269|PubMed:10608900,
CC ECO:0000269|PubMed:11139615, ECO:0000269|PubMed:11756418,
CC ECO:0000269|PubMed:12857738, ECO:0000269|PubMed:16607562,
CC ECO:0000269|PubMed:21787772, ECO:0000269|PubMed:22556419,
CC ECO:0000269|PubMed:24695224, ECO:0000269|PubMed:24695225,
CC ECO:0000269|PubMed:26999531, ECO:0000269|PubMed:28035004,
CC ECO:0000269|PubMed:30304478, ECO:0000269|PubMed:7782328,
CC ECO:0000269|PubMed:8226881};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:31576;
CC Evidence={ECO:0000305|PubMed:10373420};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=8-oxo-dATP + H2O = 8-oxo-dAMP + diphosphate + H(+);
CC Xref=Rhea:RHEA:65396, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378,
CC ChEBI:CHEBI:33019, ChEBI:CHEBI:71361, ChEBI:CHEBI:172871;
CC Evidence={ECO:0000269|PubMed:11139615};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:65397;
CC Evidence={ECO:0000305|PubMed:11139615};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=H2O + O(6)-methyl-dGTP = diphosphate + H(+) + O(6)-methyl-
CC dGMP; Xref=Rhea:RHEA:67600, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378,
CC ChEBI:CHEBI:33019, ChEBI:CHEBI:169974, ChEBI:CHEBI:169975;
CC Evidence={ECO:0000269|PubMed:30304478};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:67601;
CC Evidence={ECO:0000305|PubMed:30304478};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=H2O + N(6)-methyl-dATP = diphosphate + H(+) + N(6)-methyl-
CC dAMP; Xref=Rhea:RHEA:67604, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378,
CC ChEBI:CHEBI:33019, ChEBI:CHEBI:169976, ChEBI:CHEBI:172872;
CC Evidence={ECO:0000269|PubMed:32144205};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:67605;
CC Evidence={ECO:0000305|PubMed:32144205};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=H2O + N(6)-methyl-ATP = diphosphate + H(+) + N(6)-methyl-AMP;
CC Xref=Rhea:RHEA:67608, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378,
CC ChEBI:CHEBI:33019, ChEBI:CHEBI:144842, ChEBI:CHEBI:172873;
CC Evidence={ECO:0000269|PubMed:32144205};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:67609;
CC Evidence={ECO:0000305|PubMed:32144205};
CC -!- COFACTOR:
CC Name=Mg(2+); Xref=ChEBI:CHEBI:18420;
CC Evidence={ECO:0000250|UniProtKB:Q7ZWC3, ECO:0000305|PubMed:15133035};
CC Note=Binds 2 Mg(2+) ion per subunit. {ECO:0000250|UniProtKB:Q7ZWC3,
CC ECO:0000305|PubMed:15133035};
CC -!- ACTIVITY REGULATION: Inhibited by 2-oxo-dADP and 8-oxo-dGDP.
CC {ECO:0000269|PubMed:10373420}.
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC Kinetic parameters:
CC KM=8.3 uM for 2-oxo-dATP (at 30 degrees Celsius and pH 8.0)
CC {ECO:0000269|PubMed:10373420};
CC KM=5.7 uM for 2-oxo-dATP (at 30 degrees Celsius and pH 7.2)
CC {ECO:0000269|PubMed:10373420};
CC KM=4.3 uM for 2-oxo-ATP (at 30 degrees Celsius and pH 8.0)
CC {ECO:0000269|PubMed:11139615};
CC KM=13.9 uM for 8-oxo-dATP (at 30 degrees Celsius and pH 8.0)
CC {ECO:0000269|PubMed:10373420};
CC KM=15.2 uM for 8-oxo-dGTP (at 30 degrees Celsius and pH 8.0)
CC {ECO:0000269|PubMed:10373420};
CC KM=12.8 uM for 8-oxo-dGTP (at 30 degrees Celsius and pH 7.2)
CC {ECO:0000269|PubMed:10373420};
CC KM=13.2 uM for 8-oxo-dGTP (at 22 degrees Celsius and pH 7.5)
CC {ECO:0000269|PubMed:21787772};
CC KM=258 uM for dGTP (at 30 degrees Celsius and pH 8.0)
CC {ECO:0000269|PubMed:11139615};
CC KM=40.9 uM for N(6)-methyl-dATP (at pH 7.5)
CC {ECO:0000269|PubMed:32144205};
CC KM=15.6 uM for O(6)-methyl-dGTP (at 22 degrees Celsius and pH 7.5)
CC {ECO:0000269|PubMed:30304478};
CC KM=16.5 uM for O(6)-methyl-dGTP (at pH 7.5)
CC {ECO:0000269|PubMed:32144205};
CC KM=236 uM for O(6)-methyl-GTP (at 22 degrees Celsius and pH 7.5)
CC {ECO:0000269|PubMed:30304478};
CC Note=kcat is 13.9 sec(-1) with 2-oxo-dATP as substrate (at 30 degrees
CC Celsius and pH 8.0) (PubMed:10373420). kcat is 4.7 sec(-1) with 2-
CC oxo-dATP as substrate (at 30 degrees Celsius and pH 7.2)
CC (PubMed:10373420). kcat is 4.7 sec(-1) with 2-oxo-ATP as substrate
CC (at 30 degrees Celsius and pH 8.0) (PubMed:11139615). kcat is 12.3
CC sec(-1) with 8-oxo-dGTP as substrate (at 30 degrees Celsius and pH
CC 8.0) (PubMed:10373420). kcat is 2.1 sec(-1) with 8-oxo-dGTP as
CC substrate (at 30 degrees Celsius and pH 7.2) (PubMed:10373420). kcat
CC is 10.8 sec(-1) with 8-oxo-dATP as substrate (at 30 degrees Celsius
CC and pH 8.0) (PubMed:10373420). kcat is 5.4 sec(-1) with O(6)-methyl-
CC dGTP as substrate (at pH 7.5) (PubMed:32144205). kcat is 2.0 sec(-1)
CC with N(6)-methyl-dATP as substrate (at pH 7.5) (PubMed:32144205).
CC kcat is 8.2 sec(-1) with O(6)-methyl-dGTP as substrate
CC (PubMed:30304478). kcat is 0.3 sec(-1) with O(6)-methyl-GTP as
CC substrate (PubMed:30304478). Shows the best catalytic efficiency for
CC the 2-oxo-dATP substrate (PubMed:10373420, PubMed:11139615). Shows a
CC similar catalytic efficiency for 8-oxo-dGTP and O(6)-methyl-dGTP
CC (PubMed:30304478). {ECO:0000269|PubMed:10373420,
CC ECO:0000269|PubMed:11139615, ECO:0000269|PubMed:30304478,
CC ECO:0000269|PubMed:32144205};
CC pH dependence:
CC Optimum pH is 7.8-8.2 with 8-oxo-dGTP as substrate, and 8.0-8.5 with
CC 2-oxo-dATP as substrate. {ECO:0000269|PubMed:10373420,
CC ECO:0000269|PubMed:11139615, ECO:0000269|PubMed:21787772};
CC -!- SUBUNIT: Monomer. {ECO:0000269|PubMed:15133035,
CC ECO:0000269|PubMed:21787772}.
CC -!- INTERACTION:
CC P36639; V9HWA0: HEL-S-5; NbExp=3; IntAct=EBI-1048967, EBI-10207332;
CC P36639-2; Q03154: ACY1; NbExp=4; IntAct=EBI-12380931, EBI-742064;
CC P36639-2; Q8IVF7-3: FMNL3; NbExp=3; IntAct=EBI-12380931, EBI-12414373;
CC P36639-2; Q53H54: TRMT12; NbExp=3; IntAct=EBI-12380931, EBI-10242598;
CC P36639-4; P55212: CASP6; NbExp=3; IntAct=EBI-25834643, EBI-718729;
CC P36639-4; O00291: HIP1; NbExp=3; IntAct=EBI-25834643, EBI-473886;
CC P36639-4; P30519: HMOX2; NbExp=3; IntAct=EBI-25834643, EBI-712096;
CC P36639-4; P04792: HSPB1; NbExp=3; IntAct=EBI-25834643, EBI-352682;
CC P36639-4; P42858: HTT; NbExp=6; IntAct=EBI-25834643, EBI-466029;
CC P36639-4; O60333-2: KIF1B; NbExp=3; IntAct=EBI-25834643, EBI-10975473;
CC P36639-4; P13473-2: LAMP2; NbExp=3; IntAct=EBI-25834643, EBI-21591415;
CC P36639-4; P62826: RAN; NbExp=3; IntAct=EBI-25834643, EBI-286642;
CC P36639-4; Q9Y3C5: RNF11; NbExp=3; IntAct=EBI-25834643, EBI-396669;
CC P36639-4; O76024: WFS1; NbExp=3; IntAct=EBI-25834643, EBI-720609;
CC -!- SUBCELLULAR LOCATION: [Isoform p18]: Cytoplasm, cytosol
CC {ECO:0000269|PubMed:12857738, ECO:0000269|PubMed:16607562,
CC ECO:0000269|PubMed:7782328}. Mitochondrion matrix
CC {ECO:0000269|PubMed:7782328, ECO:0000305|PubMed:12857738,
CC ECO:0000305|PubMed:16607562}. Nucleus {ECO:0000269|PubMed:12857738,
CC ECO:0000269|PubMed:7782328}. Note=Mostly present in cytosol
CC (PubMed:7782328). A minor proportion is mitochondrial (PubMed:7782328).
CC A very small amount of the protein is associated with nuclei
CC (PubMed:7782328). {ECO:0000269|PubMed:16607562,
CC ECO:0000269|PubMed:7782328}.
CC -!- SUBCELLULAR LOCATION: [Isoform p26]: Mitochondrion matrix
CC {ECO:0000269|PubMed:16607562}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative initiation; Named isoforms=4;
CC Name=p18;
CC IsoId=P36639-4; Sequence=Displayed;
CC Name=p26;
CC IsoId=P36639-1; Sequence=VSP_061190;
CC Name=p22;
CC IsoId=P36639-2; Sequence=VSP_061189;
CC Name=p21;
CC IsoId=P36639-3; Sequence=VSP_061188;
CC -!- TISSUE SPECIFICITY: Widely expressed with highest expression in thymus,
CC testis, embryo and proliferating blood lymphocytes.
CC {ECO:0000269|PubMed:9211940}.
CC -!- DEVELOPMENTAL STAGE: In peripheral blood lymphocytes, expressed at much
CC higher levels in proliferating cells than in resting cells.
CC {ECO:0000269|PubMed:9211940}.
CC -!- PTM: The N-terminus is blocked.
CC -!- POLYMORPHISM: A polymorphism between Met-1 and Met-19 removes a stop
CC codon before the initiation codon for isoform p22 and gives rise to the
CC production of isoform p26. The allele frequency of isoform p26 is about
CC 20%. {ECO:0000269|PubMed:10536140}.
CC -!- MISCELLANEOUS: [Isoform p26]: Contains a predicted transit peptide (1-
CC 18) for localization to the mitochondrion. {ECO:0000255}.
CC -!- MISCELLANEOUS: [Isoform p26]: Derived from a B-type mRNA with a
CC polymorphic alteration (GU-->GC) at the beginning of exon 2c that
CC converts an in-frame UGA to CGA yielding another in-frame AUG further
CC upstream.
CC -!- SIMILARITY: Belongs to the Nudix hydrolase family. {ECO:0000305}.
CC -!- CAUTION: The role in cancer cell survival is under debate. Was
CC originally considered to play a role as a sanitizing enzyme for
CC oxidized nucleotide pools, and thus important for the survival of
CC cancer cells (PubMed:24695224, PubMed:24695225). A later study
CC indicates that NUDT1 plays a redundant role in eliminating oxidized
CC nucleotides and that it is not essential for cancer cell proliferation
CC and survival (PubMed:28679043). {ECO:0000269|PubMed:24695224,
CC ECO:0000269|PubMed:24695225, ECO:0000269|PubMed:28679043}.
CC -!- WEB RESOURCE: Name=NIEHS-SNPs;
CC URL="http://egp.gs.washington.edu/data/nudt1/";
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DR EMBL; D16581; BAA04013.1; -; mRNA.
DR EMBL; D38594; BAA07601.1; -; Genomic_DNA.
DR EMBL; AB025233; BAA83791.1; -; mRNA.
DR EMBL; AB025234; BAA83792.1; -; mRNA.
DR EMBL; AB025235; BAA83793.1; -; mRNA.
DR EMBL; AB025236; BAA83794.1; -; mRNA.
DR EMBL; AB025237; BAA83795.1; -; mRNA.
DR EMBL; AB025238; BAA83796.1; -; mRNA.
DR EMBL; AB025239; BAA83797.1; -; mRNA.
DR EMBL; AB025240; BAA83798.1; -; mRNA.
DR EMBL; AB025241; BAA83799.1; -; mRNA.
DR EMBL; AB025242; BAA83800.1; -; mRNA.
DR EMBL; DQ230907; ABB02181.1; -; Genomic_DNA.
DR EMBL; CH236953; EAL23948.1; -; Genomic_DNA.
DR EMBL; CH236953; EAL23949.1; -; Genomic_DNA.
DR EMBL; CR407655; CAG28583.1; -; mRNA.
DR EMBL; CH471144; EAW87225.1; -; Genomic_DNA.
DR EMBL; CH471144; EAW87227.1; -; Genomic_DNA.
DR EMBL; AC004971; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BC014618; AAH14618.1; -; mRNA.
DR EMBL; BC040144; AAH40144.2; -; mRNA.
DR EMBL; BC051375; AAH51375.2; -; mRNA.
DR EMBL; BC065367; AAH65367.1; -; mRNA.
DR CCDS; CCDS5329.1; -. [P36639-2]
DR CCDS; CCDS5330.1; -. [P36639-4]
DR RefSeq; NP_002443.3; NM_002452.3. [P36639-4]
DR RefSeq; NP_945186.1; NM_198948.1. [P36639-4]
DR RefSeq; NP_945187.1; NM_198949.1. [P36639-2]
DR RefSeq; NP_945188.1; NM_198950.1. [P36639-4]
DR RefSeq; NP_945190.1; NM_198952.1. [P36639-2]
DR RefSeq; NP_945191.1; NM_198953.1. [P36639-4]
DR RefSeq; NP_945192.1; NM_198954.1. [P36639-2]
DR PDB; 1IRY; NMR; -; A=1-156.
DR PDB; 3Q93; X-ray; 1.80 A; A/B=1-156.
DR PDB; 3WHW; X-ray; 2.70 A; A/B=1-156.
DR PDB; 3ZR0; X-ray; 1.80 A; A/B=1-156.
DR PDB; 3ZR1; X-ray; 1.90 A; A/B=1-156.
DR PDB; 4C9W; X-ray; 1.65 A; A=1-156.
DR PDB; 4C9X; X-ray; 1.20 A; A=1-156.
DR PDB; 4N1T; X-ray; 1.60 A; A=1-156.
DR PDB; 4N1U; X-ray; 1.60 A; A/B=1-155.
DR PDB; 5ANS; X-ray; 1.60 A; A=1-156.
DR PDB; 5ANT; X-ray; 2.00 A; A/B/C=1-156.
DR PDB; 5ANU; X-ray; 1.80 A; A=1-156.
DR PDB; 5ANV; X-ray; 1.16 A; A=1-156.
DR PDB; 5ANW; X-ray; 1.37 A; A=1-156.
DR PDB; 5FSI; X-ray; 1.63 A; A=1-156.
DR PDB; 5FSK; X-ray; 1.56 A; A=1-156.
DR PDB; 5FSL; X-ray; 1.24 A; A=1-156.
DR PDB; 5FSM; X-ray; 1.67 A; A=1-156.
DR PDB; 5FSN; X-ray; 1.69 A; A=1-156.
DR PDB; 5FSO; X-ray; 1.67 A; A=1-156.
DR PDB; 5GHI; X-ray; 1.21 A; A/B=1-156.
DR PDB; 5GHJ; X-ray; 1.20 A; A/B=1-156.
DR PDB; 5GHM; X-ray; 1.50 A; A/B=1-156.
DR PDB; 5GHN; X-ray; 1.39 A; A/B=1-156.
DR PDB; 5GHO; X-ray; 1.19 A; A/B=1-156.
DR PDB; 5GHP; X-ray; 1.19 A; A/B=1-156.
DR PDB; 5GHQ; X-ray; 1.18 A; A/B=1-156.
DR PDB; 5NGR; X-ray; 2.20 A; A/B=1-156.
DR PDB; 5NGS; X-ray; 1.85 A; A/B=1-156.
DR PDB; 5NGT; X-ray; 1.54 A; A=1-156.
DR PDB; 5NHY; X-ray; 1.72 A; A/B=1-156.
DR PDB; 5OTM; X-ray; 1.80 A; A/B=1-156.
DR PDB; 5WS7; X-ray; 1.00 A; A/B=1-156.
DR PDB; 6AA3; X-ray; 2.00 A; A=3-156.
DR PDB; 6AA4; X-ray; 1.90 A; A=3-156.
DR PDB; 6AA5; X-ray; 1.90 A; A=3-156.
DR PDB; 6EQ2; X-ray; 1.80 A; A=1-156.
DR PDB; 6EQ3; X-ray; 1.80 A; A=1-156.
DR PDB; 6EQ4; X-ray; 1.40 A; A=1-156.
DR PDB; 6EQ5; X-ray; 1.80 A; A=1-156.
DR PDB; 6EQ6; X-ray; 2.00 A; A=1-156.
DR PDB; 6EQ7; X-ray; 1.50 A; A=1-156.
DR PDB; 6F1X; X-ray; 1.90 A; A/B=1-156.
DR PDB; 6F20; X-ray; 2.00 A; A/B=1-156.
DR PDB; 6F22; X-ray; 1.55 A; A/B=1-156.
DR PDB; 6F23; X-ray; 1.84 A; A/B=1-156.
DR PDB; 6GLE; X-ray; 1.40 A; A=1-156.
DR PDB; 6GLF; X-ray; 2.00 A; A=1-156.
DR PDB; 6GLG; X-ray; 1.31 A; A=1-156.
DR PDB; 6GLH; X-ray; 1.20 A; A=1-156.
DR PDB; 6GLI; X-ray; 1.60 A; A=1-156.
DR PDB; 6GLJ; X-ray; 1.30 A; A=1-156.
DR PDB; 6GLK; X-ray; 1.50 A; A=1-156.
DR PDB; 6GLL; X-ray; 1.40 A; A/B=1-156.
DR PDB; 6GLM; X-ray; 1.60 A; A=1-156.
DR PDB; 6GLN; X-ray; 1.40 A; A=1-156.
DR PDB; 6GLO; X-ray; 1.70 A; A/B=1-156.
DR PDB; 6GLP; X-ray; 1.50 A; A/B=1-156.
DR PDB; 6GLQ; X-ray; 1.60 A; A/B=1-156.
DR PDB; 6GLR; X-ray; 1.60 A; A/B=1-156.
DR PDB; 6GLS; X-ray; 1.50 A; A/B=1-156.
DR PDB; 6GLT; X-ray; 1.60 A; A=1-156.
DR PDB; 6GLU; X-ray; 1.70 A; A=1-156.
DR PDB; 6GLV; X-ray; 1.60 A; A=1-156.
DR PDB; 6IJY; X-ray; 1.04 A; A/B=1-156.
DR PDB; 6ILI; X-ray; 1.45 A; A/B=1-156.
DR PDB; 6IMZ; X-ray; 2.10 A; A=3-156.
DR PDB; 6JVF; X-ray; 1.73 A; A/B=1-156.
DR PDB; 6JVG; X-ray; 1.84 A; A/B=1-156.
DR PDB; 6JVH; X-ray; 2.04 A; A/B=1-156.
DR PDB; 6JVI; X-ray; 2.25 A; A/B=1-156.
DR PDB; 6JVJ; X-ray; 2.30 A; A/B=1-156.
DR PDB; 6JVK; X-ray; 2.10 A; A/B=1-156.
DR PDB; 6JVL; X-ray; 1.90 A; A/B=1-156.
DR PDB; 6JVM; X-ray; 2.10 A; A/B=1-156.
DR PDB; 6JVN; X-ray; 2.10 A; A/B=1-156.
DR PDB; 6JVO; X-ray; 1.90 A; A/B=2-156.
DR PDB; 6JVP; X-ray; 2.21 A; A/B=1-156.
DR PDB; 6JVQ; X-ray; 2.20 A; A/B=1-156.
DR PDB; 6JVR; X-ray; 2.29 A; A/B=1-156.
DR PDB; 6JVS; X-ray; 2.10 A; A/B=1-156.
DR PDB; 6JVT; X-ray; 1.80 A; A/B=1-156.
DR PDB; 6QVO; X-ray; 2.45 A; A/B/C/D=1-156.
DR PDB; 6US2; X-ray; 1.80 A; A=1-156.
DR PDB; 6US3; X-ray; 1.47 A; A=1-156.
DR PDB; 6US4; X-ray; 1.95 A; A=1-156.
DR PDB; 7ESF; X-ray; 1.55 A; A=1-156.
DR PDB; 7N03; X-ray; 1.13 A; A=1-156.
DR PDB; 7N13; X-ray; 1.59 A; A/B=1-156.
DR PDBsum; 1IRY; -.
DR PDBsum; 3Q93; -.
DR PDBsum; 3WHW; -.
DR PDBsum; 3ZR0; -.
DR PDBsum; 3ZR1; -.
DR PDBsum; 4C9W; -.
DR PDBsum; 4C9X; -.
DR PDBsum; 4N1T; -.
DR PDBsum; 4N1U; -.
DR PDBsum; 5ANS; -.
DR PDBsum; 5ANT; -.
DR PDBsum; 5ANU; -.
DR PDBsum; 5ANV; -.
DR PDBsum; 5ANW; -.
DR PDBsum; 5FSI; -.
DR PDBsum; 5FSK; -.
DR PDBsum; 5FSL; -.
DR PDBsum; 5FSM; -.
DR PDBsum; 5FSN; -.
DR PDBsum; 5FSO; -.
DR PDBsum; 5GHI; -.
DR PDBsum; 5GHJ; -.
DR PDBsum; 5GHM; -.
DR PDBsum; 5GHN; -.
DR PDBsum; 5GHO; -.
DR PDBsum; 5GHP; -.
DR PDBsum; 5GHQ; -.
DR PDBsum; 5NGR; -.
DR PDBsum; 5NGS; -.
DR PDBsum; 5NGT; -.
DR PDBsum; 5NHY; -.
DR PDBsum; 5OTM; -.
DR PDBsum; 5WS7; -.
DR PDBsum; 6AA3; -.
DR PDBsum; 6AA4; -.
DR PDBsum; 6AA5; -.
DR PDBsum; 6EQ2; -.
DR PDBsum; 6EQ3; -.
DR PDBsum; 6EQ4; -.
DR PDBsum; 6EQ5; -.
DR PDBsum; 6EQ6; -.
DR PDBsum; 6EQ7; -.
DR PDBsum; 6F1X; -.
DR PDBsum; 6F20; -.
DR PDBsum; 6F22; -.
DR PDBsum; 6F23; -.
DR PDBsum; 6GLE; -.
DR PDBsum; 6GLF; -.
DR PDBsum; 6GLG; -.
DR PDBsum; 6GLH; -.
DR PDBsum; 6GLI; -.
DR PDBsum; 6GLJ; -.
DR PDBsum; 6GLK; -.
DR PDBsum; 6GLL; -.
DR PDBsum; 6GLM; -.
DR PDBsum; 6GLN; -.
DR PDBsum; 6GLO; -.
DR PDBsum; 6GLP; -.
DR PDBsum; 6GLQ; -.
DR PDBsum; 6GLR; -.
DR PDBsum; 6GLS; -.
DR PDBsum; 6GLT; -.
DR PDBsum; 6GLU; -.
DR PDBsum; 6GLV; -.
DR PDBsum; 6IJY; -.
DR PDBsum; 6ILI; -.
DR PDBsum; 6IMZ; -.
DR PDBsum; 6JVF; -.
DR PDBsum; 6JVG; -.
DR PDBsum; 6JVH; -.
DR PDBsum; 6JVI; -.
DR PDBsum; 6JVJ; -.
DR PDBsum; 6JVK; -.
DR PDBsum; 6JVL; -.
DR PDBsum; 6JVM; -.
DR PDBsum; 6JVN; -.
DR PDBsum; 6JVO; -.
DR PDBsum; 6JVP; -.
DR PDBsum; 6JVQ; -.
DR PDBsum; 6JVR; -.
DR PDBsum; 6JVS; -.
DR PDBsum; 6JVT; -.
DR PDBsum; 6QVO; -.
DR PDBsum; 6US2; -.
DR PDBsum; 6US3; -.
DR PDBsum; 6US4; -.
DR PDBsum; 7ESF; -.
DR PDBsum; 7N03; -.
DR PDBsum; 7N13; -.
DR AlphaFoldDB; P36639; -.
DR SMR; P36639; -.
DR BioGRID; 110621; 28.
DR IntAct; P36639; 29.
DR MINT; P36639; -.
DR STRING; 9606.ENSP00000380241; -.
DR BindingDB; P36639; -.
DR ChEMBL; CHEMBL3708265; -.
DR GlyGen; P36639; 1 site, 1 O-linked glycan (1 site).
DR iPTMnet; P36639; -.
DR PhosphoSitePlus; P36639; -.
DR BioMuta; NUDT1; -.
DR DMDM; 254763430; -.
DR EPD; P36639; -.
DR jPOST; P36639; -.
DR MassIVE; P36639; -.
DR MaxQB; P36639; -.
DR PaxDb; P36639; -.
DR PeptideAtlas; P36639; -.
DR PRIDE; P36639; -.
DR ProteomicsDB; 55217; -. [P36639-1]
DR ProteomicsDB; 55218; -. [P36639-2]
DR ProteomicsDB; 55219; -. [P36639-3]
DR ProteomicsDB; 55220; -. [P36639-4]
DR TopDownProteomics; P36639-4; -. [P36639-4]
DR Antibodypedia; 1866; 242 antibodies from 30 providers.
DR DNASU; 4521; -.
DR Ensembl; ENST00000339737.6; ENSP00000343439.2; ENSG00000106268.16. [P36639-4]
DR Ensembl; ENST00000343985.8; ENSP00000339503.4; ENSG00000106268.16. [P36639-2]
DR Ensembl; ENST00000356714.6; ENSP00000349148.1; ENSG00000106268.16. [P36639-4]
DR Ensembl; ENST00000397046.5; ENSP00000380239.1; ENSG00000106268.16. [P36639-4]
DR Ensembl; ENST00000397048.5; ENSP00000380241.1; ENSG00000106268.16. [P36639-2]
DR Ensembl; ENST00000397049.2; ENSP00000380242.2; ENSG00000106268.16. [P36639-4]
DR GeneID; 4521; -.
DR KEGG; hsa:4521; -.
DR MANE-Select; ENST00000356714.6; ENSP00000349148.1; NM_002452.4; NP_002443.3.
DR UCSC; uc003slr.1; human. [P36639-4]
DR CTD; 4521; -.
DR DisGeNET; 4521; -.
DR GeneCards; NUDT1; -.
DR HGNC; HGNC:8048; NUDT1.
DR HPA; ENSG00000106268; Tissue enhanced (bone).
DR MIM; 600312; gene.
DR neXtProt; NX_P36639; -.
DR OpenTargets; ENSG00000106268; -.
DR PharmGKB; PA31830; -.
DR VEuPathDB; HostDB:ENSG00000106268; -.
DR eggNOG; ENOG502S254; Eukaryota.
DR GeneTree; ENSGT00390000000341; -.
DR HOGENOM; CLU_037162_11_1_1; -.
DR InParanoid; P36639; -.
DR PhylomeDB; P36639; -.
DR TreeFam; TF106348; -.
DR BioCyc; MetaCyc:HS02879-MON; -.
DR BRENDA; 3.6.1.55; 2681.
DR BRENDA; 3.6.1.56; 2681.
DR PathwayCommons; P36639; -.
DR Reactome; R-HSA-2393930; Phosphate bond hydrolysis by NUDT proteins.
DR SABIO-RK; P36639; -.
DR SignaLink; P36639; -.
DR BioGRID-ORCS; 4521; 11 hits in 1083 CRISPR screens.
DR ChiTaRS; NUDT1; human.
DR EvolutionaryTrace; P36639; -.
DR GeneWiki; NUDT1; -.
DR GenomeRNAi; 4521; -.
DR Pharos; P36639; Tchem.
DR PRO; PR:P36639; -.
DR Proteomes; UP000005640; Chromosome 7.
DR RNAct; P36639; protein.
DR Bgee; ENSG00000106268; Expressed in right testis and 140 other tissues.
DR ExpressionAtlas; P36639; baseline and differential.
DR Genevisible; P36639; HS.
DR GO; GO:0001669; C:acrosomal vesicle; IEA:Ensembl.
DR GO; GO:0005737; C:cytoplasm; IDA:UniProtKB.
DR GO; GO:0005829; C:cytosol; IDA:HPA.
DR GO; GO:0005615; C:extracellular space; IEA:Ensembl.
DR GO; GO:0005759; C:mitochondrial matrix; IDA:UniProtKB.
DR GO; GO:0005739; C:mitochondrion; IDA:UniProtKB.
DR GO; GO:0031965; C:nuclear membrane; IEA:Ensembl.
DR GO; GO:0005634; C:nucleus; IDA:UniProtKB.
DR GO; GO:0005886; C:plasma membrane; IEA:Ensembl.
DR GO; GO:0106377; F:2-hydroxy-ATP hydrolase activity; IDA:UniProtKB.
DR GO; GO:0106378; F:2-hydroxy-dATP hydrolase activity; IDA:UniProtKB.
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:0047693; F:ATP diphosphatase activity; IDA:UniProtKB.
DR GO; GO:0008828; F:dATP pyrophosphohydrolase activity; IDA:GO_Central.
DR GO; GO:0016818; F:hydrolase activity, acting on acid anhydrides, in phosphorus-containing anhydrides; IBA:GO_Central.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0030515; F:snoRNA binding; ISS:UniProtKB.
DR GO; GO:0007568; P:aging; IEA:Ensembl.
DR GO; GO:0042262; P:DNA protection; IDA:UniProtKB.
DR GO; GO:0006281; P:DNA repair; IC:UniProtKB.
DR GO; GO:0008584; P:male gonad development; IEA:Ensembl.
DR GO; GO:0006152; P:purine nucleoside catabolic process; IDA:UniProtKB.
DR GO; GO:0046686; P:response to cadmium ion; IEA:Ensembl.
DR GO; GO:0006979; P:response to oxidative stress; TAS:ProtInc.
DR InterPro; IPR003563; 8ODP.
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; PR01403; 8OXTPHPHTASE.
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 3D-structure; Alternative initiation; Cytoplasm; Direct protein sequencing;
KW Hydrolase; Magnesium; Metal-binding; Mitochondrion; Nucleus;
KW Reference proteome; RNA-binding; Transit peptide.
FT CHAIN 1..156
FT /note="Oxidized purine nucleoside triphosphate hydrolase"
FT /id="PRO_0000019944"
FT DOMAIN 3..132
FT /note="Nudix hydrolase"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00794"
FT MOTIF 37..58
FT /note="Nudix box"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00794"
FT BINDING 8
FT /ligand="2-oxo-dATP"
FT /ligand_id="ChEBI:CHEBI:77897"
FT /evidence="ECO:0000269|PubMed:28035004,
FT ECO:0007744|PDB:5GHJ, ECO:0007744|PDB:5GHN,
FT ECO:0007744|PDB:5GHQ, ECO:0007744|PDB:5WS7"
FT BINDING 8
FT /ligand="8-oxo-dGMP"
FT /ligand_id="ChEBI:CHEBI:63224"
FT /evidence="ECO:0000269|PubMed:21787772,
FT ECO:0007744|PDB:3ZR0"
FT BINDING 8
FT /ligand="8-oxo-dGTP"
FT /ligand_id="ChEBI:CHEBI:77896"
FT /evidence="ECO:0000269|PubMed:26999531,
FT ECO:0000269|PubMed:28035004, ECO:0007744|PDB:5FSI,
FT ECO:0007744|PDB:5GHI"
FT BINDING 8
FT /ligand="N(6)-methyl-AMP"
FT /ligand_id="ChEBI:CHEBI:144842"
FT /evidence="ECO:0000269|PubMed:32144205,
FT ECO:0007744|PDB:6QVO"
FT BINDING 8
FT /ligand="O(6)-methyl-dGMP"
FT /ligand_id="ChEBI:CHEBI:169975"
FT /evidence="ECO:0000269|PubMed:30304478,
FT ECO:0007744|PDB:5OTM"
FT BINDING 23
FT /ligand="8-oxo-dGMP"
FT /ligand_id="ChEBI:CHEBI:63224"
FT /evidence="ECO:0000269|PubMed:21787772,
FT ECO:0007744|PDB:3ZR0"
FT BINDING 23
FT /ligand="8-oxo-dGTP"
FT /ligand_id="ChEBI:CHEBI:77896"
FT /evidence="ECO:0000269|PubMed:28035004,
FT ECO:0007744|PDB:5GHI"
FT BINDING 23
FT /ligand="N(6)-methyl-AMP"
FT /ligand_id="ChEBI:CHEBI:144842"
FT /evidence="ECO:0000269|PubMed:32144205,
FT ECO:0007744|PDB:6QVO"
FT BINDING 23
FT /ligand="O(6)-methyl-dGMP"
FT /ligand_id="ChEBI:CHEBI:169975"
FT /evidence="ECO:0000269|PubMed:30304478,
FT ECO:0007744|PDB:5OTM"
FT BINDING 27
FT /ligand="8-oxo-ATP"
FT /ligand_id="ChEBI:CHEBI:189076"
FT /evidence="ECO:0000269|PubMed:26999531,
FT ECO:0007744|PDB:5FSK"
FT BINDING 33
FT /ligand="2-oxo-dATP"
FT /ligand_id="ChEBI:CHEBI:77897"
FT /evidence="ECO:0000269|PubMed:28035004,
FT ECO:0007744|PDB:5GHJ, ECO:0007744|PDB:5GHQ"
FT BINDING 33
FT /ligand="8-oxo-dGMP"
FT /ligand_id="ChEBI:CHEBI:63224"
FT /evidence="ECO:0000269|PubMed:21787772,
FT ECO:0007744|PDB:3ZR0"
FT BINDING 33
FT /ligand="8-oxo-dGTP"
FT /ligand_id="ChEBI:CHEBI:77896"
FT /evidence="ECO:0000269|PubMed:26999531,
FT ECO:0000269|PubMed:28035004, ECO:0007744|PDB:5FSI,
FT ECO:0007744|PDB:5GHI, ECO:0007744|PDB:5GHM,
FT ECO:0007744|PDB:5GHO"
FT BINDING 33
FT /ligand="O(6)-methyl-dGMP"
FT /ligand_id="ChEBI:CHEBI:169975"
FT /evidence="ECO:0000269|PubMed:30304478,
FT ECO:0007744|PDB:5OTM"
FT BINDING 35..38
FT /ligand="2-oxo-dATP"
FT /ligand_id="ChEBI:CHEBI:77897"
FT /evidence="ECO:0000269|PubMed:28035004,
FT ECO:0007744|PDB:5GHJ, ECO:0007744|PDB:5GHN,
FT ECO:0007744|PDB:5GHQ, ECO:0007744|PDB:5WS7"
FT BINDING 35..38
FT /ligand="8-oxo-ATP"
FT /ligand_id="ChEBI:CHEBI:189076"
FT /evidence="ECO:0000269|PubMed:26999531,
FT ECO:0007744|PDB:5FSK"
FT BINDING 35..38
FT /ligand="8-oxo-dGTP"
FT /ligand_id="ChEBI:CHEBI:77896"
FT /evidence="ECO:0000269|PubMed:26999531,
FT ECO:0000269|PubMed:28035004, ECO:0007744|PDB:5FSI,
FT ECO:0007744|PDB:5GHI, ECO:0007744|PDB:5GHM"
FT BINDING 36
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /ligand_label="1"
FT /evidence="ECO:0000250|UniProtKB:Q7ZWC3"
FT BINDING 52
FT /ligand="8-oxo-ATP"
FT /ligand_id="ChEBI:CHEBI:189076"
FT /evidence="ECO:0000269|PubMed:26999531,
FT ECO:0007744|PDB:5FSK"
FT BINDING 52
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /ligand_label="2"
FT /evidence="ECO:0000250|UniProtKB:Q7ZWC3"
FT BINDING 55
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /ligand_label="2"
FT /evidence="ECO:0000250|UniProtKB:Q7ZWC3"
FT BINDING 56
FT /ligand="8-oxo-ATP"
FT /ligand_id="ChEBI:CHEBI:189076"
FT /evidence="ECO:0000269|PubMed:26999531,
FT ECO:0007744|PDB:5FSK"
FT BINDING 56
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /ligand_label="1"
FT /evidence="ECO:0000250|UniProtKB:Q7ZWC3"
FT BINDING 100
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /ligand_label="1"
FT /evidence="ECO:0000250|UniProtKB:Q7ZWC3"
FT BINDING 117..120
FT /ligand="2-oxo-dATP"
FT /ligand_id="ChEBI:CHEBI:77897"
FT /evidence="ECO:0000269|PubMed:28035004,
FT ECO:0007744|PDB:5GHJ, ECO:0007744|PDB:5GHN,
FT ECO:0007744|PDB:5GHQ, ECO:0007744|PDB:5WS7"
FT BINDING 117..120
FT /ligand="8-oxo-ATP"
FT /ligand_id="ChEBI:CHEBI:189076"
FT /evidence="ECO:0000269|PubMed:26999531,
FT ECO:0007744|PDB:5FSK"
FT BINDING 117..120
FT /ligand="8-oxo-dGMP"
FT /ligand_id="ChEBI:CHEBI:63224"
FT /evidence="ECO:0000269|PubMed:21787772,
FT ECO:0007744|PDB:3ZR0"
FT BINDING 117..120
FT /ligand="8-oxo-dGTP"
FT /ligand_id="ChEBI:CHEBI:77896"
FT /evidence="ECO:0000269|PubMed:26999531,
FT ECO:0000269|PubMed:28035004, ECO:0007744|PDB:5FSI,
FT ECO:0007744|PDB:5GHI, ECO:0007744|PDB:5GHM,
FT ECO:0007744|PDB:5GHO"
FT BINDING 117..120
FT /ligand="N(6)-methyl-AMP"
FT /ligand_id="ChEBI:CHEBI:144842"
FT /evidence="ECO:0000269|PubMed:32144205,
FT ECO:0007744|PDB:6QVO"
FT BINDING 117..120
FT /ligand="O(6)-methyl-dGMP"
FT /ligand_id="ChEBI:CHEBI:169975"
FT /evidence="ECO:0000269|PubMed:30304478,
FT ECO:0007744|PDB:5OTM"
FT VAR_SEQ 1
FT /note="M -> MGEPEGSWSGKNPGTM (in isoform p21)"
FT /id="VSP_061188"
FT VAR_SEQ 1
FT /note="M -> MSGISPQQMGEPEGSWSGKNPGTM (in isoform p22)"
FT /id="VSP_061189"
FT VAR_SEQ 1
FT /note="M -> MYWSNQITRRLGERVQGFMSGISPQQMGEPEGSWSGKNPGTM (in
FT isoform p26)"
FT /id="VSP_061190"
FT VARIANT 36
FT /note="G -> W (in dbSNP:rs11547459)"
FT /id="VAR_068715"
FT VARIANT 83
FT /note="V -> M (associated with type I diabetes in Japanese
FT female population; may be associated with an increased risk
FT for small cell lung carcinoma (SCLC); decreased
FT localization to mitochondrion; dbSNP:rs4866)"
FT /evidence="ECO:0000269|PubMed:15489334,
FT ECO:0000269|PubMed:15516784, ECO:0000269|PubMed:16607562,
FT ECO:0000269|PubMed:16774934, ECO:0000269|PubMed:9211940"
FT /id="VAR_013757"
FT MUTAGEN 27
FT /note="F->A: Reduces 2-oxo-dATPase and 8-oxo-dGTPase
FT activities."
FT /evidence="ECO:0000269|PubMed:11756418"
FT MUTAGEN 36
FT /note="G->R: Reduces activity by 97%."
FT /evidence="ECO:0000269|PubMed:10608900"
FT MUTAGEN 37
FT /note="G->F: Loss of activity."
FT /evidence="ECO:0000269|PubMed:10608900"
FT MUTAGEN 39
FT /note="V->E: Loss of activity."
FT /evidence="ECO:0000269|PubMed:10608900"
FT MUTAGEN 40
FT /note="Q->P: Reduces activity by 97%."
FT /evidence="ECO:0000269|PubMed:10608900"
FT MUTAGEN 42
FT /note="G->I: Reduces activity by 60%."
FT /evidence="ECO:0000269|PubMed:10608900"
FT MUTAGEN 45
FT /note="I->K: Loss of activity."
FT /evidence="ECO:0000269|PubMed:10608900"
FT MUTAGEN 47
FT /note="D->P: Loss of activity."
FT /evidence="ECO:0000269|PubMed:10608900"
FT MUTAGEN 48
FT /note="G->M: Loss of activity."
FT /evidence="ECO:0000269|PubMed:10608900"
FT MUTAGEN 49
FT /note="A->P: Loss of activity."
FT /evidence="ECO:0000269|PubMed:10608900"
FT MUTAGEN 53
FT /note="L->P: Loss of activity."
FT /evidence="ECO:0000269|PubMed:10608900"
FT MUTAGEN 54
FT /note="Q->P: Loss of activity."
FT /evidence="ECO:0000269|PubMed:10608900"
FT MUTAGEN 55
FT /note="E->G: Loss of activity."
FT /evidence="ECO:0000269|PubMed:10608900"
FT MUTAGEN 56
FT /note="E->A: Loss of ability to prevent DNA damage.
FT Expected to cause loss of enzyme activity."
FT /evidence="ECO:0000269|PubMed:24695224"
FT MUTAGEN 56
FT /note="E->Y: Loss of activity."
FT /evidence="ECO:0000269|PubMed:10608900"
FT MUTAGEN 57
FT /note="S->R: Loss of activity."
FT /evidence="ECO:0000269|PubMed:10608900"
FT MUTAGEN 117
FT /note="W->A: Greatly reduces or abolishes 2-oxo-dATPase and
FT 8-oxo-dGTPase activities."
FT /evidence="ECO:0000269|PubMed:11756418"
FT MUTAGEN 117
FT /note="W->Y: Enhances 2-oxo-dATPase activity and greatly
FT reduces 8-oxo-dGTPase activity."
FT /evidence="ECO:0000269|PubMed:11756418"
FT MUTAGEN 119
FT /note="D->A,N: Loss of 2-oxo-dATPase activity, reduces 8-
FT oxo-dGTPase activity."
FT /evidence="ECO:0000269|PubMed:11756418"
FT MUTAGEN 120
FT /note="D->A,N: Mildly decreased 2-oxo-dATPase activity,
FT nearly abolishes 8-oxo-dGTPase activity."
FT /evidence="ECO:0000269|PubMed:28035004"
FT MUTAGEN 150
FT /note="L->A: Reduces 2-oxo-dATPase and 8-oxo-dGTPase
FT activities and increases thermolability."
FT /evidence="ECO:0000269|PubMed:11756418"
FT MUTAGEN 151..156
FT /note="Missing: Almost abolishes 2-oxo-dATPase and 8-oxo-
FT dGTPase activities and increases thermolability."
FT /evidence="ECO:0000269|PubMed:11756418"
FT MUTAGEN 151
FT /note="R->A: Reduces 2-oxo-dATPase and 8-oxo-dGTPase
FT activities and increases thermolability."
FT /evidence="ECO:0000269|PubMed:11756418"
FT MUTAGEN 152..156
FT /note="Missing: Greatly reduces 2-oxo-dATPase and 8-oxo-
FT dGTPase activities and increases thermolability."
FT /evidence="ECO:0000269|PubMed:11756418"
FT MUTAGEN 152
FT /note="E->A: Reduces 2-oxo-dATPase and 8-oxo-dGTPase
FT activities and increases thermolability."
FT /evidence="ECO:0000269|PubMed:11756418"
FT MUTAGEN 153..156
FT /note="Missing: Reduces 2-oxo-dATPase and 8-oxo-dGTPase
FT activities and increases thermolability."
FT /evidence="ECO:0000269|PubMed:11756418"
FT MUTAGEN 153
FT /note="V->A: Reduces 2-oxo-dATPase and 8-oxo-dGTPase
FT activities and increases thermolability."
FT /evidence="ECO:0000269|PubMed:11756418"
FT MUTAGEN 154..156
FT /note="Missing: Slightly enhances 2-oxo-dATPase and 8-oxo-
FT dGTPase activities and increases thermolability."
FT /evidence="ECO:0000269|PubMed:11756418"
FT MUTAGEN 154
FT /note="D->A: Enhances 2-oxo-dATPase and 8-oxo-dGTPase
FT activities and increases thermolability."
FT /evidence="ECO:0000269|PubMed:11756418"
FT MUTAGEN 155
FT /note="T->A: Reduces 2-oxo-dATPase and 8-oxo-dGTPase
FT activities and increases thermolability."
FT /evidence="ECO:0000269|PubMed:11756418"
FT MUTAGEN 156
FT /note="V->A: Slightly reduces 2-oxo-dATPase and 8-oxo-
FT dGTPase activities and increases thermolability."
FT /evidence="ECO:0000269|PubMed:11756418"
FT STRAND 4..13
FT /evidence="ECO:0007829|PDB:5WS7"
FT STRAND 15..23
FT /evidence="ECO:0007829|PDB:5WS7"
FT TURN 27..30
FT /evidence="ECO:0007829|PDB:5WS7"
FT STRAND 31..33
FT /evidence="ECO:0007829|PDB:6IJY"
FT STRAND 35..38
FT /evidence="ECO:0007829|PDB:7N03"
FT HELIX 45..57
FT /evidence="ECO:0007829|PDB:5WS7"
FT STRAND 60..62
FT /evidence="ECO:0007829|PDB:6IJY"
FT STRAND 64..74
FT /evidence="ECO:0007829|PDB:5WS7"
FT STRAND 79..90
FT /evidence="ECO:0007829|PDB:5WS7"
FT STRAND 91..93
FT /evidence="ECO:0007829|PDB:6IJY"
FT STRAND 99..107
FT /evidence="ECO:0007829|PDB:5WS7"
FT HELIX 108..110
FT /evidence="ECO:0007829|PDB:7N03"
FT HELIX 113..115
FT /evidence="ECO:0007829|PDB:5WS7"
FT HELIX 120..128
FT /evidence="ECO:0007829|PDB:5WS7"
FT STRAND 132..140
FT /evidence="ECO:0007829|PDB:5WS7"
FT TURN 141..143
FT /evidence="ECO:0007829|PDB:5WS7"
FT STRAND 144..154
FT /evidence="ECO:0007829|PDB:5WS7"
SQ SEQUENCE 156 AA; 17952 MW; B9FB669FF0ACFF5F CRC64;
MGASRLYTLV LVLQPQRVLL GMKKRGFGAG RWNGFGGKVQ EGETIEDGAR RELQEESGLT
VDALHKVGQI VFEFVGEPEL MDVHVFCTDS IQGTPVESDE MRPCWFQLDQ IPFKDMWPDD
SYWFPLLLQK KKFHGYFKFQ GQDTILDYTL REVDTV
