8ODP_DANRE
ID 8ODP_DANRE Reviewed; 156 AA.
AC Q7ZWC3;
DT 29-SEP-2021, integrated into UniProtKB/Swiss-Prot.
DT 01-JUN-2003, sequence version 1.
DT 03-AUG-2022, entry version 139.
DE RecName: Full=Oxidized purine nucleoside triphosphate hydrolase;
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;
OS Danio rerio (Zebrafish) (Brachydanio rerio).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
OC Actinopterygii; Neopterygii; Teleostei; Ostariophysi; Cypriniformes;
OC Danionidae; Danioninae; Danio.
OX NCBI_TaxID=7955;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=Tuebingen;
RX PubMed=23594743; DOI=10.1038/nature12111;
RA Howe K., Clark M.D., Torroja C.F., Torrance J., Berthelot C., Muffato M.,
RA Collins J.E., Humphray S., McLaren K., Matthews L., McLaren S., Sealy I.,
RA Caccamo M., Churcher C., Scott C., Barrett J.C., Koch R., Rauch G.J.,
RA White S., Chow W., Kilian B., Quintais L.T., Guerra-Assuncao J.A., Zhou Y.,
RA Gu Y., Yen J., Vogel J.H., Eyre T., Redmond S., Banerjee R., Chi J., Fu B.,
RA Langley E., Maguire S.F., Laird G.K., Lloyd D., Kenyon E., Donaldson S.,
RA Sehra H., Almeida-King J., Loveland J., Trevanion S., Jones M., Quail M.,
RA Willey D., Hunt A., Burton J., Sims S., McLay K., Plumb B., Davis J.,
RA Clee C., Oliver K., Clark R., Riddle C., Elliot D., Threadgold G.,
RA Harden G., Ware D., Begum S., Mortimore B., Kerry G., Heath P.,
RA Phillimore B., Tracey A., Corby N., Dunn M., Johnson C., Wood J., Clark S.,
RA Pelan S., Griffiths G., Smith M., Glithero R., Howden P., Barker N.,
RA Lloyd C., Stevens C., Harley J., Holt K., Panagiotidis G., Lovell J.,
RA Beasley H., Henderson C., Gordon D., Auger K., Wright D., Collins J.,
RA Raisen C., Dyer L., Leung K., Robertson L., Ambridge K., Leongamornlert D.,
RA McGuire S., Gilderthorp R., Griffiths C., Manthravadi D., Nichol S.,
RA Barker G., Whitehead S., Kay M., Brown J., Murnane C., Gray E.,
RA Humphries M., Sycamore N., Barker D., Saunders D., Wallis J., Babbage A.,
RA Hammond S., Mashreghi-Mohammadi M., Barr L., Martin S., Wray P.,
RA Ellington A., Matthews N., Ellwood M., Woodmansey R., Clark G., Cooper J.,
RA Tromans A., Grafham D., Skuce C., Pandian R., Andrews R., Harrison E.,
RA Kimberley A., Garnett J., Fosker N., Hall R., Garner P., Kelly D., Bird C.,
RA Palmer S., Gehring I., Berger A., Dooley C.M., Ersan-Urun Z., Eser C.,
RA Geiger H., Geisler M., Karotki L., Kirn A., Konantz J., Konantz M.,
RA Oberlander M., Rudolph-Geiger S., Teucke M., Lanz C., Raddatz G.,
RA Osoegawa K., Zhu B., Rapp A., Widaa S., Langford C., Yang F.,
RA Schuster S.C., Carter N.P., Harrow J., Ning Z., Herrero J., Searle S.M.,
RA Enright A., Geisler R., Plasterk R.H., Lee C., Westerfield M.,
RA de Jong P.J., Zon L.I., Postlethwait J.H., Nusslein-Volhard C.,
RA Hubbard T.J., Roest Crollius H., Rogers J., Stemple D.L.;
RT "The zebrafish reference genome sequence and its relationship to the human
RT genome.";
RL Nature 496:498-503(2013).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Embryo;
RG NIH - Zebrafish Gene Collection (ZGC) project;
RL Submitted (MAR-2003) to the EMBL/GenBank/DDBJ databases.
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:5HZX}
RP X-RAY CRYSTALLOGRAPHY (1.90 ANGSTROMS) IN COMPLEX WITH INHIBITOR, FUNCTION,
RP CATALYTIC ACTIVITY, BIOPHYSICOCHEMICAL PROPERTIES, AND ACTIVITY REGULATION.
RX PubMed=26862114; DOI=10.1158/0008-5472.can-15-2380;
RA Brautigam L., Pudelko L., Jemth A.S., Gad H., Narwal M., Gustafsson R.,
RA Karsten S., Carreras-Puigvert J., Homan E., Berndt C., Warpman Berglund U.,
RA Stenmark P., Helleday T.;
RT "Hypoxic Signaling and the Cellular Redox Tumor Environment Determine
RT Sensitivity to MTH1 Inhibition.";
RL Cancer Res. 76:2366-2375(2016).
RN [5] {ECO:0007744|PDB:5OTN}
RP X-RAY CRYSTALLOGRAPHY (0.99 ANGSTROMS) IN COMPLEX WITH O(6)-METHYL-DGMP AND
RP COFACTOR, FUNCTION, CATALYTIC ACTIVITY, 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).
CC -!- FUNCTION: Oxidized purine nucleoside triphosphate hydrolase which is a
CC prominent sanitizer of the oxidized nucleotide pool (PubMed:26862114,
CC PubMed:30304478). Catalyzes the hydrolysis of 2-oxo-dATP (2-hydroxy-
CC dATP) into 2-oxo-dAMP (PubMed:26862114). Has also a significant
CC hydrolase activity toward 2-oxo-ATP, 8-oxo-dGTP and 8-oxo-dATP
CC (PubMed:26862114, PubMed:30304478). Through the hydrolysis of oxidized
CC purine nucleoside triphosphates, prevents their incorporation into DNA
CC and the subsequent transversions A:T to C:G and G:C to T:A
CC (PubMed:26862114, PubMed:30304478). Also catalyzes the hydrolysis of
CC methylated purine nucleoside triphosphate preventing their integration
CC into DNA (PubMed:32144205, PubMed:30304478). Through this antimutagenic
CC activity protects cells from oxidative stress (PubMed:32144205,
CC PubMed:26862114, PubMed:30304478). {ECO:0000269|PubMed:26862114,
CC ECO:0000269|PubMed:30304478, 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:0000269|PubMed:26862114};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:31584;
CC Evidence={ECO:0000305|PubMed:26862114};
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:26862114};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:31576;
CC Evidence={ECO:0000305|PubMed:26862114};
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:30304478};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:65397;
CC Evidence={ECO:0000305|PubMed:30304478};
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:0000269|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:0000269|PubMed:30304478, ECO:0007744|PDB:5OTN};
CC Note=Binds 2 Mg(2+) ion per subunit. {ECO:0000269|PubMed:30304478,
CC ECO:0007744|PDB:5OTN};
CC -!- ACTIVITY REGULATION: Inhibited by TH588. {ECO:0000269|PubMed:26862114}.
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC Kinetic parameters:
CC KM=3.9 uM for 8-oxo-dGTP (at pH 7.5) {ECO:0000269|PubMed:26862114};
CC KM=6.1 uM for 2-oxo-dATP (at pH 7.5) {ECO:0000269|PubMed:26862114};
CC KM=91.4 uM for dGTP (at pH 7.5) {ECO:0000269|PubMed:26862114};
CC Note=kcat is 5.4 sec(-1) with 8-oxo-dGTP as substrate (at pH 7.5)
CC (PubMed:26862114). kcat is 12.0 sec(-1) with 2-oxo-dATP as substrate
CC (at pH 7.5) (PubMed:26862114). kcat is 7.6 sec(-1) with dGTP as
CC substrate (at pH 7.5) (PubMed:26862114). Shows the best catalytic
CC efficiency for the 8-oxo-dGTP substrate (PubMed:26862114).
CC {ECO:0000269|PubMed:26862114};
CC -!- SUBUNIT: Monomer. {ECO:0000250|UniProtKB:P36639}.
CC -!- SUBCELLULAR LOCATION: Cytoplasm, cytosol
CC {ECO:0000250|UniProtKB:P36639}. Mitochondrion matrix
CC {ECO:0000250|UniProtKB:P36639}. Nucleus {ECO:0000250|UniProtKB:P36639}.
CC -!- SIMILARITY: Belongs to the Nudix hydrolase family. {ECO:0000305}.
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DR EMBL; BX510926; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BC049486; AAH49486.1; -; mRNA.
DR RefSeq; NP_998583.1; NM_213418.1.
DR PDB; 5HZX; X-ray; 1.90 A; A/B=1-156.
DR PDB; 5OTN; X-ray; 0.99 A; A=1-156.
DR PDBsum; 5HZX; -.
DR PDBsum; 5OTN; -.
DR AlphaFoldDB; Q7ZWC3; -.
DR SMR; Q7ZWC3; -.
DR STRING; 7955.ENSDARP00000040752; -.
DR PaxDb; Q7ZWC3; -.
DR Ensembl; ENSDART00000040753; ENSDARP00000040752; ENSDARG00000030573.
DR GeneID; 406727; -.
DR KEGG; dre:406727; -.
DR CTD; 4521; -.
DR ZFIN; ZDB-GENE-040426-2757; nudt1.
DR eggNOG; ENOG502S254; Eukaryota.
DR GeneTree; ENSGT00390000000341; -.
DR HOGENOM; CLU_037162_11_1_1; -.
DR InParanoid; Q7ZWC3; -.
DR OMA; FRADSYN; -.
DR OrthoDB; 1602447at2759; -.
DR PhylomeDB; Q7ZWC3; -.
DR TreeFam; TF106348; -.
DR Reactome; R-DRE-2393930; Phosphate bond hydrolysis by NUDT proteins.
DR Proteomes; UP000000437; Genome assembly.
DR Proteomes; UP000814640; Chromosome 3.
DR Bgee; ENSDARG00000030573; Expressed in testis and 26 other tissues.
DR GO; GO:0005737; C:cytoplasm; IBA:GO_Central.
DR GO; GO:0005829; C:cytosol; IEA:UniProtKB-SubCell.
DR GO; GO:0005759; C:mitochondrial matrix; IEA:UniProtKB-SubCell.
DR GO; GO:0005634; C:nucleus; IEA:UniProtKB-SubCell.
DR GO; GO:0008413; F:8-oxo-7,8-dihydroguanosine triphosphate pyrophosphatase activity; IBA:GO_Central.
DR GO; GO:0016818; F:hydrolase activity, acting on acid anhydrides, in phosphorus-containing anhydrides; IDA:ZFIN.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0003723; F:RNA binding; IEA:UniProtKB-KW.
DR GO; GO:0042262; P:DNA protection; IBA:GO_Central.
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; Hydrolase; Magnesium; Metal-binding;
KW Mitochondrion; Nucleus; Reference proteome; RNA-binding; Transit peptide.
FT CHAIN 1..156
FT /note="Oxidized purine nucleoside triphosphate hydrolase"
FT /evidence="ECO:0000255"
FT /id="PRO_5015098920"
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 8
FT /ligand="O(6)-methyl-dGMP"
FT /ligand_id="ChEBI:CHEBI:169975"
FT /evidence="ECO:0000269|PubMed:30304478,
FT ECO:0007744|PDB:5OTN"
FT BINDING 23
FT /ligand="8-oxo-dGTP"
FT /ligand_id="ChEBI:CHEBI:77896"
FT /evidence="ECO:0000250|UniProtKB:P36639"
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:5OTN"
FT BINDING 33
FT /ligand="2-oxo-dATP"
FT /ligand_id="ChEBI:CHEBI:77897"
FT /evidence="ECO:0000250|UniProtKB:P36639"
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:5OTN"
FT BINDING 35..38
FT /ligand="2-oxo-dATP"
FT /ligand_id="ChEBI:CHEBI:77897"
FT /evidence="ECO:0000250|UniProtKB:P36639"
FT BINDING 35..38
FT /ligand="O(6)-methyl-dGMP"
FT /ligand_id="ChEBI:CHEBI:169975"
FT /evidence="ECO:0000269|PubMed:30304478,
FT ECO:0007744|PDB:5OTN"
FT BINDING 36
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /ligand_label="1"
FT /evidence="ECO:0000269|PubMed:30304478,
FT ECO:0007744|PDB:5OTN"
FT BINDING 52
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /ligand_label="2"
FT /evidence="ECO:0000269|PubMed:30304478,
FT ECO:0007744|PDB:5OTN"
FT BINDING 55
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /ligand_label="2"
FT /evidence="ECO:0000269|PubMed:30304478,
FT ECO:0007744|PDB:5OTN"
FT BINDING 56
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /ligand_label="1"
FT /evidence="ECO:0000269|PubMed:30304478,
FT ECO:0007744|PDB:5OTN"
FT BINDING 100
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /ligand_label="1"
FT /evidence="ECO:0000269|PubMed:30304478,
FT ECO:0007744|PDB:5OTN"
FT BINDING 117..120
FT /ligand="2-oxo-dATP"
FT /ligand_id="ChEBI:CHEBI:77897"
FT /evidence="ECO:0000250|UniProtKB:P36639"
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:5OTN"
FT STRAND 3..14
FT /evidence="ECO:0007829|PDB:5OTN"
FT STRAND 17..23
FT /evidence="ECO:0007829|PDB:5OTN"
FT TURN 27..30
FT /evidence="ECO:0007829|PDB:5OTN"
FT STRAND 31..33
FT /evidence="ECO:0007829|PDB:5OTN"
FT STRAND 35..38
FT /evidence="ECO:0007829|PDB:5HZX"
FT HELIX 45..57
FT /evidence="ECO:0007829|PDB:5OTN"
FT STRAND 65..74
FT /evidence="ECO:0007829|PDB:5OTN"
FT STRAND 79..90
FT /evidence="ECO:0007829|PDB:5OTN"
FT STRAND 99..107
FT /evidence="ECO:0007829|PDB:5OTN"
FT HELIX 108..110
FT /evidence="ECO:0007829|PDB:5OTN"
FT HELIX 113..115
FT /evidence="ECO:0007829|PDB:5OTN"
FT HELIX 120..128
FT /evidence="ECO:0007829|PDB:5OTN"
FT STRAND 132..140
FT /evidence="ECO:0007829|PDB:5OTN"
FT TURN 141..143
FT /evidence="ECO:0007829|PDB:5OTN"
FT STRAND 144..154
FT /evidence="ECO:0007829|PDB:5OTN"
SQ SEQUENCE 156 AA; 18022 MW; 7236B4B7864F1C0D CRC64;
MFTSKLLTLV LVVQPGRVLL GMKKRGFGAG KWNGFGGKVQ TGETIEQAAR RELLEESGLT
VDTLHKIGNI KFEFIGETEL MDVHIFRADN YEGEPAESDE MRPQWFDIDK IPFSQMWADD
ILWFPLMLQK KRFLGYFKFQ GHDVIVEHKL DEVEDL
