NQO1_MOUSE
ID NQO1_MOUSE Reviewed; 274 AA.
AC Q64669;
DT 01-NOV-1997, integrated into UniProtKB/Swiss-Prot.
DT 23-JAN-2007, sequence version 3.
DT 03-AUG-2022, entry version 174.
DE RecName: Full=NAD(P)H dehydrogenase [quinone] 1;
DE EC=1.6.5.2 {ECO:0000269|PubMed:8999809};
DE AltName: Full=Azoreductase;
DE AltName: Full=DT-diaphorase {ECO:0000303|PubMed:8999809};
DE Short=DTD;
DE AltName: Full=Menadione reductase;
DE AltName: Full=NAD(P)H:quinone oxidoreductase 1 {ECO:0000303|PubMed:10706635};
DE AltName: Full=Phylloquinone reductase;
DE AltName: Full=Quinone reductase 1;
DE Short=QR1;
GN Name=Nqo1; Synonyms=Dia4, Nmo1, Nmor1;
OS Mus musculus (Mouse).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Mus; Mus.
OX NCBI_TaxID=10090;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC STRAIN=C57BL/6 X CBA; TISSUE=Liver;
RX PubMed=7704040;
RA Vasiliou V., Theurer M.J., Puga A., Reuter S.F., Nebert D.W.;
RT "Mouse dioxin-inducible NAD(P)H: menadione oxidoreductase: NMO1 cDNA
RT sequence and genetic differences in mRNA levels.";
RL Pharmacogenetics 4:341-348(1994).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA], PARTIAL PROTEIN SEQUENCE, CLEAVAGE OF INITIATOR
RP METHIONINE, AND ACETYLATION AT ALA-2.
RC TISSUE=Liver;
RX PubMed=7527260; DOI=10.1002/pro.5560030816;
RA Chen S., Clarke P.E., Martino P.A., Deng P.S., Yeh C.H., Lee T.D.,
RA Prochaska H.J., Talalay P.;
RT "Mouse liver NAD(P)H:quinone acceptor oxidoreductase: protein sequence
RT analysis by tandem mass spectrometry, cDNA cloning, expression in
RT Escherichia coli, and enzyme activity analysis.";
RL Protein Sci. 3:1296-1304(1994).
RN [3]
RP FUNCTION, CATALYTIC ACTIVITY, AND BIOPHYSICOCHEMICAL PROPERTIES.
RX PubMed=8999809; DOI=10.1074/jbc.272.3.1437;
RA Chen S., Knox R., Wu K., Deng P.S., Zhou D., Bianchet M.A., Amzel L.M.;
RT "Molecular basis of the catalytic differences among DT-diaphorase of human,
RT rat, and mouse.";
RL J. Biol. Chem. 272:1437-1439(1997).
RN [4]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Brain, Heart, Kidney, Liver, Lung, Spleen, and Testis;
RX PubMed=21183079; DOI=10.1016/j.cell.2010.12.001;
RA Huttlin E.L., Jedrychowski M.P., Elias J.E., Goswami T., Rad R.,
RA Beausoleil S.A., Villen J., Haas W., Sowa M.E., Gygi S.P.;
RT "A tissue-specific atlas of mouse protein phosphorylation and expression.";
RL Cell 143:1174-1189(2010).
RN [5]
RP X-RAY CRYSTALLOGRAPHY (2.8 ANGSTROMS) IN COMPLEX WITH FAD, AND SUBUNIT.
RX PubMed=10706635; DOI=10.1073/pnas.97.7.3177;
RA Faig M., Bianchet M.A., Talalay P., Chen S., Winski S., Ross D.,
RA Amzel L.M.;
RT "Structures of recombinant human and mouse NAD(P)H:quinone oxidoreductases:
RT species comparison and structural changes with substrate binding and
RT release.";
RL Proc. Natl. Acad. Sci. U.S.A. 97:3177-3182(2000).
CC -!- FUNCTION: Flavin-containing quinone reductase that catalyzes two-
CC electron reduction of quinones to hydroquinones using either NADH or
CC NADPH as electron donors. In a ping-pong kinetic mechanism, the
CC electrons are sequentially transferred from NAD(P)H to flavin cofactor
CC and then from reduced flavin to the quinone, bypassing the formation of
CC semiquinone and reactive oxygen species (PubMed:8999809) (By
CC similarity). Regulates cellular redox state primarily through quinone
CC detoxification. Reduces components of plasma membrane redox system such
CC as coenzyme Q and vitamin quinones, producing antioxidant hydroquinone
CC forms. In the process may function as superoxide scavenger to prevent
CC hydroquinone oxidation and facilitate excretion (By similarity).
CC Alternatively, can activate quinones and their derivatives by
CC generating redox reactive hydroquinones with DNA cross-linking
CC antitumor potential (By similarity). Acts as a gatekeeper of the core
CC 20S proteasome known to degrade proteins with unstructured regions.
CC Upon oxidative stress, interacts with tumor suppressors TP53 and TP73
CC in a NADH-dependent way and inhibits their ubiquitin-independent
CC degradation by the 20S proteasome (By similarity).
CC {ECO:0000250|UniProtKB:P05982, ECO:0000250|UniProtKB:P15559,
CC ECO:0000269|PubMed:8999809}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=a quinone + H(+) + NADH = a quinol + NAD(+);
CC Xref=Rhea:RHEA:46160, ChEBI:CHEBI:15378, ChEBI:CHEBI:24646,
CC ChEBI:CHEBI:57540, ChEBI:CHEBI:57945, ChEBI:CHEBI:132124; EC=1.6.5.2;
CC Evidence={ECO:0000269|PubMed:8999809};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:46161;
CC Evidence={ECO:0000305|PubMed:8999809};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=a quinone + H(+) + NADPH = a quinol + NADP(+);
CC Xref=Rhea:RHEA:46164, ChEBI:CHEBI:15378, ChEBI:CHEBI:24646,
CC ChEBI:CHEBI:57783, ChEBI:CHEBI:58349, ChEBI:CHEBI:132124; EC=1.6.5.2;
CC Evidence={ECO:0000250|UniProtKB:P15559};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:46165;
CC Evidence={ECO:0000250|UniProtKB:P15559};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=H(+) + NADH + ubiquinone-10 = NAD(+) + ubiquinol-10;
CC Xref=Rhea:RHEA:61984, ChEBI:CHEBI:15378, ChEBI:CHEBI:46245,
CC ChEBI:CHEBI:57540, ChEBI:CHEBI:57945, ChEBI:CHEBI:64183;
CC Evidence={ECO:0000250|UniProtKB:P15559};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:61985;
CC Evidence={ECO:0000250|UniProtKB:P15559};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=H(+) + menadione + NADH = menadiol + NAD(+);
CC Xref=Rhea:RHEA:69695, ChEBI:CHEBI:6746, ChEBI:CHEBI:15378,
CC ChEBI:CHEBI:28869, ChEBI:CHEBI:57540, ChEBI:CHEBI:57945;
CC Evidence={ECO:0000269|PubMed:8999809};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:69696;
CC Evidence={ECO:0000305|PubMed:8999809};
CC -!- COFACTOR:
CC Name=FAD; Xref=ChEBI:CHEBI:57692;
CC Evidence={ECO:0000250|UniProtKB:P15559};
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC Kinetic parameters:
CC KM=4.3 uM for menadione {ECO:0000269|PubMed:8999809};
CC KM=210 uM for NADH {ECO:0000269|PubMed:8999809};
CC KM=1280 uM for 5-(aziridin-1-yl)-2,4-dinitrobenzamide
CC {ECO:0000269|PubMed:8999809};
CC Vmax=1800 umol/min/mg enzyme toward menadione
CC {ECO:0000269|PubMed:8999809};
CC Vmax=20 nmol/min/mg enzyme toward 5-(aziridin-1-yl)-2,4-
CC dinitrobenzamide {ECO:0000269|PubMed:8999809};
CC -!- SUBUNIT: Homodimer (PubMed:10706635). Interacts with PDLIM4 isoform 2;
CC this interaction stabilizes PDLIM4 isoform 2 in response to oxidative
CC stress and protects it from ubiquitin-independent degradation by the
CC core 20S proteasome (By similarity). Interacts with TP73 (via SAM
CC domain); this interaction is NADH-dependent, stabilizes TP73 in
CC response to oxidative stress and protects it from ubiquitin-independent
CC degradation by the 20S proteasome (By similarity). Interacts with TP53;
CC this interaction is NADH-dependent, stabilizes TP53 in response to
CC oxidative stress and protects it from ubiquitin-independent degradation
CC by the 20S proteasome (By similarity). {ECO:0000250|UniProtKB:P15559,
CC ECO:0000269|PubMed:10706635}.
CC -!- SUBCELLULAR LOCATION: Cytoplasm, cytosol
CC {ECO:0000250|UniProtKB:P05982}.
CC -!- INDUCTION: By polycyclic hydrocarbons such as dioxin (Governed by the
CC aromatic hydrocarbon-responsive (AH) locus).
CC -!- SIMILARITY: Belongs to the NAD(P)H dehydrogenase (quinone) family.
CC {ECO:0000305}.
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DR EMBL; U12961; AAA80184.1; -; mRNA.
DR EMBL; S75951; AAB32718.1; -; mRNA.
DR CCDS; CCDS40465.1; -.
DR PIR; A57691; A57691.
DR RefSeq; NP_032732.3; NM_008706.5.
DR PDB; 1DXQ; X-ray; 2.80 A; A/B/C/D=2-274.
DR PDBsum; 1DXQ; -.
DR AlphaFoldDB; Q64669; -.
DR SMR; Q64669; -.
DR BioGRID; 201790; 3.
DR STRING; 10090.ENSMUSP00000003947; -.
DR ChEMBL; CHEMBL5611; -.
DR iPTMnet; Q64669; -.
DR PhosphoSitePlus; Q64669; -.
DR CPTAC; non-CPTAC-4052; -.
DR jPOST; Q64669; -.
DR MaxQB; Q64669; -.
DR PaxDb; Q64669; -.
DR PRIDE; Q64669; -.
DR ProteomicsDB; 293965; -.
DR Antibodypedia; 1549; 823 antibodies from 43 providers.
DR DNASU; 18104; -.
DR Ensembl; ENSMUST00000003947; ENSMUSP00000003947; ENSMUSG00000003849.
DR GeneID; 18104; -.
DR KEGG; mmu:18104; -.
DR UCSC; uc009nhq.1; mouse.
DR CTD; 1728; -.
DR MGI; MGI:103187; Nqo1.
DR VEuPathDB; HostDB:ENSMUSG00000003849; -.
DR eggNOG; ENOG502QQMI; Eukaryota.
DR GeneTree; ENSGT00940000159150; -.
DR HOGENOM; CLU_058643_2_0_1; -.
DR InParanoid; Q64669; -.
DR OMA; WFERVLV; -.
DR OrthoDB; 1394543at2759; -.
DR PhylomeDB; Q64669; -.
DR TreeFam; TF300296; -.
DR BRENDA; 1.6.5.2; 3474.
DR Reactome; R-MMU-350562; Regulation of ornithine decarboxylase (ODC).
DR BioGRID-ORCS; 18104; 2 hits in 77 CRISPR screens.
DR ChiTaRS; Nqo1; mouse.
DR EvolutionaryTrace; Q64669; -.
DR PRO; PR:Q64669; -.
DR Proteomes; UP000000589; Chromosome 8.
DR RNAct; Q64669; protein.
DR Bgee; ENSMUSG00000003849; Expressed in epithelium of stomach and 166 other tissues.
DR ExpressionAtlas; Q64669; baseline and differential.
DR Genevisible; Q64669; MM.
DR GO; GO:0005737; C:cytoplasm; ISO:MGI.
DR GO; GO:0005829; C:cytosol; ISO:MGI.
DR GO; GO:0030425; C:dendrite; ISO:MGI.
DR GO; GO:0043025; C:neuronal cell body; ISO:MGI.
DR GO; GO:0042802; F:identical protein binding; ISO:MGI.
DR GO; GO:0003955; F:NAD(P)H dehydrogenase (quinone) activity; IDA:MGI.
DR GO; GO:0050136; F:NADH dehydrogenase (quinone) activity; IDA:UniProtKB.
DR GO; GO:0008753; F:NADPH dehydrogenase (quinone) activity; IEA:RHEA.
DR GO; GO:0004784; F:superoxide dismutase activity; ISO:MGI.
DR GO; GO:0007568; P:aging; IEA:Ensembl.
DR GO; GO:0045454; P:cell redox homeostasis; IEA:Ensembl.
DR GO; GO:0070301; P:cellular response to hydrogen peroxide; ISO:MGI.
DR GO; GO:0071248; P:cellular response to metal ion; IEA:Ensembl.
DR GO; GO:0034599; P:cellular response to oxidative stress; ISS:UniProtKB.
DR GO; GO:0006116; P:NADH oxidation; ISO:MGI.
DR GO; GO:0070995; P:NADPH oxidation; ISO:MGI.
DR GO; GO:0043066; P:negative regulation of apoptotic process; ISO:MGI.
DR GO; GO:0043086; P:negative regulation of catalytic activity; IDA:MGI.
DR GO; GO:0042177; P:negative regulation of protein catabolic process; ISS:UniProtKB.
DR GO; GO:0043525; P:positive regulation of neuron apoptotic process; ISO:MGI.
DR GO; GO:0019430; P:removal of superoxide radicals; ISS:UniProtKB.
DR GO; GO:0043279; P:response to alkaloid; IEA:Ensembl.
DR GO; GO:0014075; P:response to amine; ISO:MGI.
DR GO; GO:0009743; P:response to carbohydrate; IEA:Ensembl.
DR GO; GO:0051602; P:response to electrical stimulus; IEA:Ensembl.
DR GO; GO:0032355; P:response to estradiol; IEA:Ensembl.
DR GO; GO:0045471; P:response to ethanol; IEA:Ensembl.
DR GO; GO:1905395; P:response to flavonoid; IEA:Ensembl.
DR GO; GO:0009725; P:response to hormone; IEA:Ensembl.
DR GO; GO:1904880; P:response to hydrogen sulfide; IEA:Ensembl.
DR GO; GO:0002931; P:response to ischemia; IEA:Ensembl.
DR GO; GO:1904844; P:response to L-glutamine; ISO:MGI.
DR GO; GO:0007584; P:response to nutrient; IEA:Ensembl.
DR GO; GO:0006979; P:response to oxidative stress; IMP:MGI.
DR GO; GO:0033574; P:response to testosterone; IEA:Ensembl.
DR GO; GO:1904772; P:response to tetrachloromethane; IEA:Ensembl.
DR GO; GO:0009410; P:response to xenobiotic stimulus; ISO:MGI.
DR GO; GO:0006801; P:superoxide metabolic process; ISO:MGI.
DR GO; GO:0006743; P:ubiquinone metabolic process; ISS:UniProtKB.
DR GO; GO:0042360; P:vitamin E metabolic process; ISS:UniProtKB.
DR GO; GO:0042373; P:vitamin K metabolic process; IDA:UniProtKB.
DR Gene3D; 3.40.50.360; -; 1.
DR InterPro; IPR003680; Flavodoxin_fold.
DR InterPro; IPR029039; Flavoprotein-like_sf.
DR Pfam; PF02525; Flavodoxin_2; 1.
DR SUPFAM; SSF52218; SSF52218; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Acetylation; Cytoplasm; Direct protein sequencing; FAD;
KW Flavoprotein; Isopeptide bond; NAD; NADP; Oxidoreductase; Phosphoprotein;
KW Reference proteome; Ubl conjugation.
FT INIT_MET 1
FT /note="Removed"
FT /evidence="ECO:0000269|PubMed:7527260"
FT CHAIN 2..274
FT /note="NAD(P)H dehydrogenase [quinone] 1"
FT /id="PRO_0000071623"
FT REGION 225..274
FT /note="Important for apoenzyme conformational stability"
FT /evidence="ECO:0000250|UniProtKB:P15559"
FT BINDING 12
FT /ligand="FAD"
FT /ligand_id="ChEBI:CHEBI:57692"
FT /evidence="ECO:0000269|PubMed:10706635"
FT BINDING 18..19
FT /ligand="FAD"
FT /ligand_id="ChEBI:CHEBI:57692"
FT /evidence="ECO:0000269|PubMed:10706635"
FT BINDING 67
FT /ligand="FAD"
FT /ligand_id="ChEBI:CHEBI:57692"
FT /evidence="ECO:0000269|PubMed:10706635"
FT BINDING 104..107
FT /ligand="FAD"
FT /ligand_id="ChEBI:CHEBI:57692"
FT /evidence="ECO:0000269|PubMed:10706635"
FT BINDING 126..128
FT /ligand="substrate"
FT /evidence="ECO:0000250"
FT BINDING 148..151
FT /ligand="FAD"
FT /ligand_id="ChEBI:CHEBI:57692"
FT /evidence="ECO:0000269|PubMed:10706635"
FT BINDING 156
FT /ligand="FAD"
FT /ligand_id="ChEBI:CHEBI:57692"
FT /evidence="ECO:0000269|PubMed:10706635"
FT BINDING 201
FT /ligand="FAD"
FT /ligand_id="ChEBI:CHEBI:57692"
FT /evidence="ECO:0000269|PubMed:10706635"
FT MOD_RES 2
FT /note="N-acetylalanine"
FT /evidence="ECO:0000269|PubMed:7527260"
FT MOD_RES 82
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P15559"
FT CROSSLNK 251
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO2)"
FT /evidence="ECO:0000250|UniProtKB:P15559"
FT STRAND 5..10
FT /evidence="ECO:0007829|PDB:1DXQ"
FT HELIX 18..32
FT /evidence="ECO:0007829|PDB:1DXQ"
FT STRAND 36..41
FT /evidence="ECO:0007829|PDB:1DXQ"
FT HELIX 42..45
FT /evidence="ECO:0007829|PDB:1DXQ"
FT HELIX 68..77
FT /evidence="ECO:0007829|PDB:1DXQ"
FT HELIX 83..94
FT /evidence="ECO:0007829|PDB:1DXQ"
FT STRAND 96..103
FT /evidence="ECO:0007829|PDB:1DXQ"
FT HELIX 111..120
FT /evidence="ECO:0007829|PDB:1DXQ"
FT TURN 123..125
FT /evidence="ECO:0007829|PDB:1DXQ"
FT STRAND 129..131
FT /evidence="ECO:0007829|PDB:1DXQ"
FT HELIX 133..135
FT /evidence="ECO:0007829|PDB:1DXQ"
FT TURN 137..140
FT /evidence="ECO:0007829|PDB:1DXQ"
FT STRAND 141..151
FT /evidence="ECO:0007829|PDB:1DXQ"
FT HELIX 153..156
FT /evidence="ECO:0007829|PDB:1DXQ"
FT STRAND 160..162
FT /evidence="ECO:0007829|PDB:1DXQ"
FT HELIX 165..173
FT /evidence="ECO:0007829|PDB:1DXQ"
FT TURN 174..176
FT /evidence="ECO:0007829|PDB:1DXQ"
FT HELIX 177..180
FT /evidence="ECO:0007829|PDB:1DXQ"
FT STRAND 188..191
FT /evidence="ECO:0007829|PDB:1DXQ"
FT TURN 193..195
FT /evidence="ECO:0007829|PDB:1DXQ"
FT HELIX 198..212
FT /evidence="ECO:0007829|PDB:1DXQ"
FT HELIX 213..217
FT /evidence="ECO:0007829|PDB:1DXQ"
FT HELIX 226..228
FT /evidence="ECO:0007829|PDB:1DXQ"
FT TURN 233..236
FT /evidence="ECO:0007829|PDB:1DXQ"
FT STRAND 237..239
FT /evidence="ECO:0007829|PDB:1DXQ"
FT HELIX 241..247
FT /evidence="ECO:0007829|PDB:1DXQ"
FT STRAND 254..256
FT /evidence="ECO:0007829|PDB:1DXQ"
FT TURN 268..270
FT /evidence="ECO:0007829|PDB:1DXQ"
SQ SEQUENCE 274 AA; 30960 MW; 68F380922FD72965 CRC64;
MAARRALIVL AHSEKTSFNY AMKEAAVEAL KKRGWEVLES DLYAMNFNPI ISRNDITGEL
KDSKNFQYPS ESSLAYKEGR LSPDIVAEHK KLEAADLVIF QFPLQWFGVP AILKGWFERV
LVAGFAYTYA AMYDNGPFQN KKTLLSITTG GSGSMYSLQG VHGDMNVILW PIQSGILRFC
GFQVLEPQLV YSIGHTPPDA RMQILEGWKK RLETVWEETP LYFAPSSLFD LNFQAGFLMK
KEVQEEQKKN KFGLSVGHHL GKSIPADNQI KARK
