8ODP_CANLF
ID 8ODP_CANLF Reviewed; 156 AA.
AC F1P963;
DT 23-MAY-2018, integrated into UniProtKB/Swiss-Prot.
DT 23-MAY-2018, sequence version 2.
DT 03-AUG-2022, entry version 64.
DE RecName: Full=Oxidized purine nucleoside triphosphate hydrolase {ECO:0000305};
DE EC=3.6.1.56 {ECO:0000250|UniProtKB:P36639};
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:0000250|UniProtKB:P36639};
DE EC=3.6.1.- {ECO:0000250|UniProtKB:P36639};
DE AltName: Full=Nucleoside diphosphate-linked moiety X motif 1;
DE Short=Nudix motif 1;
GN Name=NUDT1; Synonyms=MTH1 {ECO:0000303|PubMed:29281266};
OS Canis lupus familiaris (Dog) (Canis familiaris).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Laurasiatheria; Carnivora; Caniformia; Canidae; Canis.
OX NCBI_TaxID=9615 {ECO:0000312|Proteomes:UP000002254};
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=Boxer;
RX PubMed=16341006; DOI=10.1038/nature04338;
RA Lindblad-Toh K., Wade C.M., Mikkelsen T.S., Karlsson E.K., Jaffe D.B.,
RA Kamal M., Clamp M., Chang J.L., Kulbokas E.J. III, Zody M.C., Mauceli E.,
RA Xie X., Breen M., Wayne R.K., Ostrander E.A., Ponting C.P., Galibert F.,
RA Smith D.R., deJong P.J., Kirkness E.F., Alvarez P., Biagi T., Brockman W.,
RA Butler J., Chin C.-W., Cook A., Cuff J., Daly M.J., DeCaprio D., Gnerre S.,
RA Grabherr M., Kellis M., Kleber M., Bardeleben C., Goodstadt L., Heger A.,
RA Hitte C., Kim L., Koepfli K.-P., Parker H.G., Pollinger J.P.,
RA Searle S.M.J., Sutter N.B., Thomas R., Webber C., Baldwin J., Abebe A.,
RA Abouelleil A., Aftuck L., Ait-Zahra M., Aldredge T., Allen N., An P.,
RA Anderson S., Antoine C., Arachchi H., Aslam A., Ayotte L., Bachantsang P.,
RA Barry A., Bayul T., Benamara M., Berlin A., Bessette D., Blitshteyn B.,
RA Bloom T., Blye J., Boguslavskiy L., Bonnet C., Boukhgalter B., Brown A.,
RA Cahill P., Calixte N., Camarata J., Cheshatsang Y., Chu J., Citroen M.,
RA Collymore A., Cooke P., Dawoe T., Daza R., Decktor K., DeGray S.,
RA Dhargay N., Dooley K., Dooley K., Dorje P., Dorjee K., Dorris L.,
RA Duffey N., Dupes A., Egbiremolen O., Elong R., Falk J., Farina A., Faro S.,
RA Ferguson D., Ferreira P., Fisher S., FitzGerald M., Foley K., Foley C.,
RA Franke A., Friedrich D., Gage D., Garber M., Gearin G., Giannoukos G.,
RA Goode T., Goyette A., Graham J., Grandbois E., Gyaltsen K., Hafez N.,
RA Hagopian D., Hagos B., Hall J., Healy C., Hegarty R., Honan T., Horn A.,
RA Houde N., Hughes L., Hunnicutt L., Husby M., Jester B., Jones C., Kamat A.,
RA Kanga B., Kells C., Khazanovich D., Kieu A.C., Kisner P., Kumar M.,
RA Lance K., Landers T., Lara M., Lee W., Leger J.-P., Lennon N., Leuper L.,
RA LeVine S., Liu J., Liu X., Lokyitsang Y., Lokyitsang T., Lui A.,
RA Macdonald J., Major J., Marabella R., Maru K., Matthews C., McDonough S.,
RA Mehta T., Meldrim J., Melnikov A., Meneus L., Mihalev A., Mihova T.,
RA Miller K., Mittelman R., Mlenga V., Mulrain L., Munson G., Navidi A.,
RA Naylor J., Nguyen T., Nguyen N., Nguyen C., Nguyen T., Nicol R., Norbu N.,
RA Norbu C., Novod N., Nyima T., Olandt P., O'Neill B., O'Neill K., Osman S.,
RA Oyono L., Patti C., Perrin D., Phunkhang P., Pierre F., Priest M.,
RA Rachupka A., Raghuraman S., Rameau R., Ray V., Raymond C., Rege F.,
RA Rise C., Rogers J., Rogov P., Sahalie J., Settipalli S., Sharpe T.,
RA Shea T., Sheehan M., Sherpa N., Shi J., Shih D., Sloan J., Smith C.,
RA Sparrow T., Stalker J., Stange-Thomann N., Stavropoulos S., Stone C.,
RA Stone S., Sykes S., Tchuinga P., Tenzing P., Tesfaye S., Thoulutsang D.,
RA Thoulutsang Y., Topham K., Topping I., Tsamla T., Vassiliev H.,
RA Venkataraman V., Vo A., Wangchuk T., Wangdi T., Weiand M., Wilkinson J.,
RA Wilson A., Yadav S., Yang S., Yang X., Young G., Yu Q., Zainoun J.,
RA Zembek L., Zimmer A., Lander E.S.;
RT "Genome sequence, comparative analysis and haplotype structure of the
RT domestic dog.";
RL Nature 438:803-819(2005).
RN [2]
RP FUNCTION, AND CATALYTIC ACTIVITY.
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 [3]
RP FUNCTION, AND CATALYTIC ACTIVITY.
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 [4] {ECO:0007744|PDB:5MZF}
RP X-RAY CRYSTALLOGRAPHY (2.00 ANGSTROMS), CATALYTIC ACTIVITY, FUNCTION, AND
RP SUBUNIT.
RX PubMed=29281266; DOI=10.1021/acs.biochem.7b01163;
RA Narwal M., Jemth A.S., Gustafsson R., Almlof I., Warpman Berglund U.,
RA Helleday T., Stenmark P.;
RT "Crystal Structures and Inhibitor Interactions of Mouse and Dog MTH1 Reveal
RT Species-Specific Differences in Affinity.";
RL Biochemistry 57:593-603(2018).
CC -!- FUNCTION: Oxidized purine nucleoside triphosphate hydrolase which is a
CC prominent sanitizer of the oxidized nucleotide pool (PubMed:30304478,
CC PubMed:32144205, PubMed:29281266). Catalyzes the hydrolysis of 2-oxo-
CC dATP (2-hydroxy-dATP) into 2-oxo-dAMP (By similarity). Has also a
CC significant hydrolase activity toward 2-oxo-ATP, 8-oxo-dGTP and 8-oxo-
CC dATP (PubMed:30304478, PubMed:32144205, PubMed:29281266). Through the
CC hydrolysis of oxidized purine nucleoside triphosphates, prevents their
CC incorporation into DNA and the subsequent transversions A:T to C:G and
CC G:C to T:A (PubMed:30304478, PubMed:32144205, PubMed:29281266). Also
CC catalyzes the hydrolysis of methylated purine nucleoside triphosphate
CC preventing their integration into DNA (PubMed:30304478,
CC PubMed:32144205). Through this antimutagenic activity protects cells
CC from oxidative stress (PubMed:30304478, PubMed:32144205,
CC PubMed:29281266). {ECO:0000250|UniProtKB:P36639,
CC ECO:0000269|PubMed:29281266, ECO:0000269|PubMed:30304478,
CC ECO:0000269|PubMed:32144205}.
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:0000250|UniProtKB:P36639};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:31584;
CC Evidence={ECO:0000250|UniProtKB:P36639};
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:0000250|UniProtKB:P36639};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:67393;
CC Evidence={ECO:0000250|UniProtKB:P36639};
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:29281266, ECO:0000269|PubMed:30304478,
CC ECO:0000269|PubMed:32144205};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:31576;
CC Evidence={ECO:0000305|PubMed:29281266};
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:0000250|UniProtKB:P36639};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:65397;
CC Evidence={ECO:0000250|UniProtKB:P36639};
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:0000250|UniProtKB:P36639};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:67609;
CC Evidence={ECO:0000250|UniProtKB:P36639};
CC -!- COFACTOR:
CC Name=Mg(2+); Xref=ChEBI:CHEBI:18420;
CC Evidence={ECO:0000250|UniProtKB:Q7ZWC3};
CC Note=Binds 2 Mg(2+) ion per subunit. {ECO:0000250|UniProtKB:Q7ZWC3};
CC -!- SUBUNIT: Monomer. {ECO:0000305|PubMed:29281266}.
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000250|UniProtKB:P53369}. Nucleus
CC {ECO:0000250|UniProtKB:P53369}. Nucleus membrane
CC {ECO:0000250|UniProtKB:P53369}. Cytoplasmic vesicle, secretory vesicle,
CC acrosome {ECO:0000250|UniProtKB:P53369}.
CC -!- SIMILARITY: Belongs to the Nudix hydrolase family. {ECO:0000305}.
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DR EMBL; AAEX03004329; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR RefSeq; XP_547012.4; XM_547012.4.
DR PDB; 5MZF; X-ray; 2.00 A; A/B/C/D=1-156.
DR PDBsum; 5MZF; -.
DR AlphaFoldDB; F1P963; -.
DR SMR; F1P963; -.
DR STRING; 9615.ENSCAFP00000054594; -.
DR PaxDb; F1P963; -.
DR Ensembl; ENSCAFT00040039181; ENSCAFP00040034170; ENSCAFG00040021127.
DR GeneID; 489894; -.
DR KEGG; cfa:489894; -.
DR CTD; 4521; -.
DR eggNOG; ENOG502S254; Eukaryota.
DR HOGENOM; CLU_037162_11_1_1; -.
DR InParanoid; F1P963; -.
DR OrthoDB; 1602447at2759; -.
DR TreeFam; TF106348; -.
DR BRENDA; 3.6.1.56; 1153.
DR Reactome; R-CFA-2393930; Phosphate bond hydrolysis by NUDT proteins.
DR Proteomes; UP000002254; Unplaced.
DR GO; GO:0001669; C:acrosomal vesicle; IEA:UniProtKB-SubCell.
DR GO; GO:0005737; C:cytoplasm; IBA:GO_Central.
DR GO; GO:0005829; C:cytosol; IEA:Ensembl.
DR GO; GO:0005759; C:mitochondrial matrix; IEA:Ensembl.
DR GO; GO:0031965; C:nuclear membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0106377; F:2-hydroxy-ATP hydrolase activity; ISS:UniProtKB.
DR GO; GO:0106378; F:2-hydroxy-dATP hydrolase activity; ISS:UniProtKB.
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; IBA:GO_Central.
DR GO; GO:0047693; F:ATP diphosphatase activity; IEA:Ensembl.
DR GO; GO:0008828; F:dATP pyrophosphohydrolase activity; IEA:UniProtKB-EC.
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; IEA:Ensembl.
DR GO; GO:0042262; P:DNA protection; IBA:GO_Central.
DR GO; GO:0006152; P:purine nucleoside catabolic process; ISS:UniProtKB.
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; Cytoplasm; Cytoplasmic vesicle; Hydrolase; Magnesium;
KW Membrane; Metal-binding; Nucleus; Reference proteome; RNA-binding.
FT CHAIN 1..156
FT /note="Oxidized purine nucleoside triphosphate hydrolase"
FT /id="PRO_0000444047"
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:0000250|UniProtKB:P36639"
FT BINDING 23
FT /ligand="8-oxo-dGTP"
FT /ligand_id="ChEBI:CHEBI:77896"
FT /evidence="ECO:0000250|UniProtKB:P36639"
FT BINDING 33
FT /ligand="2-oxo-dATP"
FT /ligand_id="ChEBI:CHEBI:77897"
FT /evidence="ECO:0000250|UniProtKB:P36639"
FT BINDING 35..38
FT /ligand="2-oxo-dATP"
FT /ligand_id="ChEBI:CHEBI:77897"
FT /evidence="ECO:0000250|UniProtKB:P36639"
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="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="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:0000250|UniProtKB:P36639"
FT STRAND 4..13
FT /evidence="ECO:0007829|PDB:5MZF"
FT STRAND 15..23
FT /evidence="ECO:0007829|PDB:5MZF"
FT TURN 27..30
FT /evidence="ECO:0007829|PDB:5MZF"
FT STRAND 31..33
FT /evidence="ECO:0007829|PDB:5MZF"
FT STRAND 35..38
FT /evidence="ECO:0007829|PDB:5MZF"
FT HELIX 45..57
FT /evidence="ECO:0007829|PDB:5MZF"
FT STRAND 65..74
FT /evidence="ECO:0007829|PDB:5MZF"
FT STRAND 78..89
FT /evidence="ECO:0007829|PDB:5MZF"
FT STRAND 99..107
FT /evidence="ECO:0007829|PDB:5MZF"
FT HELIX 113..115
FT /evidence="ECO:0007829|PDB:5MZF"
FT HELIX 120..128
FT /evidence="ECO:0007829|PDB:5MZF"
FT STRAND 133..140
FT /evidence="ECO:0007829|PDB:5MZF"
FT TURN 141..143
FT /evidence="ECO:0007829|PDB:5MZF"
FT STRAND 144..152
FT /evidence="ECO:0007829|PDB:5MZF"
SQ SEQUENCE 156 AA; 18080 MW; F6D1BC96957B764E CRC64;
MGTSRLYTLV LVLQPERVLL GMKKRGFGAG RWNGFGGKVQ EGETIEDGAK RELREESGLT
VDTLHKVGQI MFEFVGEPEL MDVHIFCTDS VQGTPVESDE MRPQWFQLDQ IPFTDMWPDD
SYWFPLLLQK KKFHGYFRFQ GPNTILDYTL REVDKL
