8ODP_RAT
ID 8ODP_RAT Reviewed; 156 AA.
AC P53369;
DT 01-OCT-1996, integrated into UniProtKB/Swiss-Prot.
DT 01-OCT-1996, sequence version 1.
DT 03-AUG-2022, entry version 128.
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;
OS Rattus norvegicus (Rat).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Rattus.
OX NCBI_TaxID=10116;
RN [1]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA / MRNA], FUNCTION, CATALYTIC ACTIVITY, AND
RP TISSUE SPECIFICITY.
RC STRAIN=Donryu; TISSUE=Spleen;
RX PubMed=7586133; DOI=10.1093/carcin/16.10.2343;
RA Cai J.P., Kakuma T., Tsuzuki T., Sekiguchi M.;
RT "cDNA and genomic sequences for rat 8-oxo-dGTPase that prevents occurrence
RT of spontaneous mutations due to oxidation of guanine nucleotides.";
RL Carcinogenesis 16:2343-2350(1995).
RN [2]
RP SUBCELLULAR LOCATION, AND TISSUE SPECIFICITY.
RX PubMed=11817101; DOI=10.1078/0940-2993-00201;
RA Kasprzak K.S., Nakabeppu Y., Kakuma T., Sakai Y., Tsuruya K., Sekiguchi M.,
RA Ward J.M., Diwan B.A., Nagashima K., Kasprzak B.H.;
RT "Intracellular distribution of the antimutagenic enzyme MTH1 in the liver,
RT kidney and testis of F344 rats and its modulation by cadmium.";
RL Exp. Toxicol. Pathol. 53:325-335(2001).
RN [3]
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 [4]
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).
CC -!- FUNCTION: Oxidized purine nucleoside triphosphate hydrolase which is a
CC prominent sanitizer of the oxidized nucleotide pool (PubMed:7586133).
CC Catalyzes the hydrolysis of 2-oxo-dATP (2-hydroxy-dATP) into 2-oxo-dAMP
CC (PubMed:7586133). Has also a significant hydrolase activity toward 2-
CC oxo-ATP, 8-oxo-dGTP and 8-oxo-dATP (By similarity). 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:7586133). Also catalyzes the hydrolysis of
CC methylated purine nucleoside triphosphate preventing their integration
CC into DNA (PubMed:30304478, PubMed:32144205). Through this antimutagenic
CC activity protects cells from oxidative stress (PubMed:7586133,
CC PubMed:30304478, PubMed:32144205). {ECO:0000250|UniProtKB:P36639,
CC ECO:0000269|PubMed:30304478, ECO:0000269|PubMed:32144205,
CC ECO:0000269|PubMed:7586133}.
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:30304478, ECO:0000269|PubMed:7586133};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:31576;
CC Evidence={ECO:0000305|PubMed:7586133};
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:0000250|UniProtKB:P36639}.
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000269|PubMed:11817101}. Nucleus
CC {ECO:0000269|PubMed:11817101}. Nucleus membrane
CC {ECO:0000269|PubMed:11817101}. Cytoplasmic vesicle, secretory vesicle,
CC acrosome {ECO:0000269|PubMed:11817101}.
CC -!- TISSUE SPECIFICITY: Expressed in liver in hepatocytes and weakly in
CC Kupffer's cells. Expression detected in testes in primary and secondary
CC spermatocytes and interstitial cells. High expression levels detected
CC in the inner cortex of kidney, with lower levels detected in the
CC tubules of the outer cortex, medulla, renal pelvis and glomeruli (at
CC protein level). Expressed in heart, brain, spleen, lung, liver,
CC skeletal muscle, kidney and testis. {ECO:0000269|PubMed:11817101,
CC ECO:0000269|PubMed:7586133}.
CC -!- SIMILARITY: Belongs to the Nudix hydrolase family. {ECO:0000305}.
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DR EMBL; D49977; BAA08726.1; -; mRNA.
DR EMBL; D49980; BAA08727.1; -; Genomic_DNA.
DR RefSeq; NP_476461.1; NM_057120.1.
DR RefSeq; XP_006248973.1; XM_006248911.3.
DR AlphaFoldDB; P53369; -.
DR SMR; P53369; -.
DR STRING; 10116.ENSRNOP00000001700; -.
DR PhosphoSitePlus; P53369; -.
DR jPOST; P53369; -.
DR PaxDb; P53369; -.
DR Ensembl; ENSRNOT00000001700; ENSRNOP00000001700; ENSRNOG00000001260.
DR GeneID; 117260; -.
DR KEGG; rno:117260; -.
DR UCSC; RGD:621080; rat.
DR CTD; 4521; -.
DR RGD; 621080; Nudt1.
DR eggNOG; ENOG502S254; Eukaryota.
DR GeneTree; ENSGT00390000000341; -.
DR HOGENOM; CLU_037162_11_1_1; -.
DR InParanoid; P53369; -.
DR OMA; FRADSYN; -.
DR OrthoDB; 1602447at2759; -.
DR PhylomeDB; P53369; -.
DR TreeFam; TF106348; -.
DR Reactome; R-RNO-2393930; Phosphate bond hydrolysis by NUDT proteins.
DR PRO; PR:P53369; -.
DR Proteomes; UP000002494; Chromosome 12.
DR Bgee; ENSRNOG00000001260; Expressed in thymus and 19 other tissues.
DR Genevisible; P53369; RN.
DR GO; GO:0001669; C:acrosomal vesicle; IDA:RGD.
DR GO; GO:0005737; C:cytoplasm; IDA:RGD.
DR GO; GO:0005829; C:cytosol; IEA:Ensembl.
DR GO; GO:0005615; C:extracellular space; IDA:RGD.
DR GO; GO:0005759; C:mitochondrial matrix; ISS:UniProtKB.
DR GO; GO:0005739; C:mitochondrion; ISS:UniProtKB.
DR GO; GO:0031965; C:nuclear membrane; IDA:RGD.
DR GO; GO:0005634; C:nucleus; IDA:RGD.
DR GO; GO:0005886; C:plasma membrane; IDA:RGD.
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; ISS:UniProtKB.
DR GO; GO:0047693; F:ATP diphosphatase activity; ISO:RGD.
DR GO; GO:0008828; F:dATP pyrophosphohydrolase activity; ISO:RGD.
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; IEP:RGD.
DR GO; GO:0042262; P:DNA protection; ISS:UniProtKB.
DR GO; GO:0008584; P:male gonad development; IEP:RGD.
DR GO; GO:0006152; P:purine nucleoside catabolic process; ISS:UniProtKB.
DR GO; GO:0046686; P:response to cadmium ion; IEP:RGD.
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 Cytoplasm; Cytoplasmic vesicle; Hydrolase; Magnesium; Membrane;
KW Metal-binding; Nucleus; Reference proteome; RNA-binding.
FT CHAIN 1..156
FT /note="Oxidized purine nucleoside triphosphate hydrolase"
FT /id="PRO_0000057101"
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"
SQ SEQUENCE 156 AA; 18018 MW; 60AFB6522CB03E18 CRC64;
MSTSRLYTLV LVLQPQRVLL GMKKRGFGAG RWNGFGGKVQ EGETIEDGAK RELLEESGLR
VDTLHKVGHI SFEFVGSPEL MDVHIFSTDH VHGTPTESEE MRPQWFQLDQ IPFADMWPDD
SYWFPLLLQK KKFCGHFKFH GQDTILSYSL REVDEF
