NQO1_HUMAN
ID NQO1_HUMAN Reviewed; 274 AA.
AC P15559; B2R5Y9; B4DNM7; B7ZAD1; Q86UK1;
DT 01-APR-1990, integrated into UniProtKB/Swiss-Prot.
DT 01-APR-1990, sequence version 1.
DT 03-AUG-2022, entry version 224.
DE RecName: Full=NAD(P)H dehydrogenase [quinone] 1;
DE EC=1.6.5.2 {ECO:0000269|PubMed:8999809, ECO:0000269|PubMed:9271353};
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:1657151};
DE AltName: Full=Phylloquinone reductase;
DE AltName: Full=Quinone reductase 1;
DE Short=QR1;
GN Name=NQO1 {ECO:0000303|PubMed:1657151, ECO:0000312|HGNC:HGNC:2874};
GN Synonyms=DIA4, NMOR1;
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 1).
RC TISSUE=Liver;
RX PubMed=2843525; DOI=10.1016/s0021-9258(18)68280-8;
RA Jaiswal A.K., McBride O.W., Adesnik M., Nebert D.W.;
RT "Human dioxin-inducible cytosolic NAD(P)H:menadione oxidoreductase. cDNA
RT sequence and localization of gene to chromosome 16.";
RL J. Biol. Chem. 263:13572-13578(1988).
RN [2]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND INDUCTION.
RX PubMed=1657151; DOI=10.1021/bi00108a007;
RA Jaiswal A.K.;
RT "Human NAD(P)H:quinone oxidoreductase (NQO1) gene structure and induction
RT by dioxin.";
RL Biochemistry 30:10647-10653(1991).
RN [3]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND VARIANT SER-187.
RG NIEHS SNPs program;
RL Submitted (APR-2003) to the EMBL/GenBank/DDBJ databases.
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1; 2 AND 3), AND VARIANT
RP SER-187.
RC TISSUE=Amygdala;
RX PubMed=14702039; DOI=10.1038/ng1285;
RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R.,
RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H.,
RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.,
RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K.,
RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H.,
RA Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M.,
RA Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K.,
RA Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T.,
RA Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M.,
RA Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S.,
RA Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H.,
RA Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K.,
RA Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N.,
RA Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S.,
RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O.,
RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H.,
RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B.,
RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y.,
RA Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K.,
RA Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T.,
RA Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T.,
RA Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y.,
RA Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H.,
RA Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y.,
RA Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H.,
RA Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O.,
RA Isogai T., Sugano S.;
RT "Complete sequencing and characterization of 21,243 full-length human
RT cDNAs.";
RL Nat. Genet. 36:40-45(2004).
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=15616553; DOI=10.1038/nature03187;
RA Martin J., Han C., Gordon L.A., Terry A., Prabhakar S., She X., Xie G.,
RA Hellsten U., Chan Y.M., Altherr M., Couronne O., Aerts A., Bajorek E.,
RA Black S., Blumer H., Branscomb E., Brown N.C., Bruno W.J., Buckingham J.M.,
RA Callen D.F., Campbell C.S., Campbell M.L., Campbell E.W., Caoile C.,
RA Challacombe J.F., Chasteen L.A., Chertkov O., Chi H.C., Christensen M.,
RA Clark L.M., Cohn J.D., Denys M., Detter J.C., Dickson M.,
RA Dimitrijevic-Bussod M., Escobar J., Fawcett J.J., Flowers D., Fotopulos D.,
RA Glavina T., Gomez M., Gonzales E., Goodstein D., Goodwin L.A., Grady D.L.,
RA Grigoriev I., Groza M., Hammon N., Hawkins T., Haydu L., Hildebrand C.E.,
RA Huang W., Israni S., Jett J., Jewett P.B., Kadner K., Kimball H.,
RA Kobayashi A., Krawczyk M.-C., Leyba T., Longmire J.L., Lopez F., Lou Y.,
RA Lowry S., Ludeman T., Manohar C.F., Mark G.A., McMurray K.L., Meincke L.J.,
RA Morgan J., Moyzis R.K., Mundt M.O., Munk A.C., Nandkeshwar R.D.,
RA Pitluck S., Pollard M., Predki P., Parson-Quintana B., Ramirez L., Rash S.,
RA Retterer J., Ricke D.O., Robinson D.L., Rodriguez A., Salamov A.,
RA Saunders E.H., Scott D., Shough T., Stallings R.L., Stalvey M.,
RA Sutherland R.D., Tapia R., Tesmer J.G., Thayer N., Thompson L.S., Tice H.,
RA Torney D.C., Tran-Gyamfi M., Tsai M., Ulanovsky L.E., Ustaszewska A.,
RA Vo N., White P.S., Williams A.L., Wills P.L., Wu J.-R., Wu K., Yang J.,
RA DeJong P., Bruce D., Doggett N.A., Deaven L., Schmutz J., Grimwood J.,
RA Richardson P., Rokhsar D.S., Eichler E.E., Gilna P., Lucas S.M.,
RA Myers R.M., Rubin E.M., Pennacchio L.A.;
RT "The sequence and analysis of duplication-rich human chromosome 16.";
RL Nature 432:988-994(2004).
RN [6]
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 [7]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC TISSUE=Colon;
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 [8]
RP FUNCTION, CATALYTIC ACTIVITY, BIOPHYSICOCHEMICAL PROPERTIES, AND
RP MUTAGENESIS OF GLN-105 AND ILE-204.
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 [9]
RP FUNCTION, CATALYTIC ACTIVITY, AND ACTIVITY REGULATION.
RX PubMed=9271353; DOI=10.1124/mol.52.2.300;
RA Siegel D., Bolton E.M., Burr J.A., Liebler D.C., Ross D.;
RT "The reduction of alpha-tocopherolquinone by human NAD(P)H: quinone
RT oxidoreductase: the role of alpha-tocopherolhydroquinone as a cellular
RT antioxidant.";
RL Mol. Pharmacol. 52:300-305(1997).
RN [10]
RP FUNCTION.
RX PubMed=15102952; DOI=10.1124/mol.65.5.1238;
RA Siegel D., Gustafson D.L., Dehn D.L., Han J.Y., Boonchoong P.,
RA Berliner L.J., Ross D.;
RT "NAD(P)H:quinone oxidoreductase 1: role as a superoxide scavenger.";
RL Mol. Pharmacol. 65:1238-1247(2004).
RN [11]
RP FUNCTION, ACTIVITY REGULATION, MUTAGENESIS OF TYR-129, AND INTERACTION WITH
RP TP53 AND TP73.
RX PubMed=15687255; DOI=10.1101/gad.319905;
RA Asher G., Tsvetkov P., Kahana C., Shaul Y.;
RT "A mechanism of ubiquitin-independent proteasomal degradation of the tumor
RT suppressors p53 and p73.";
RL Genes Dev. 19:316-321(2005).
RN [12]
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 [13]
RP INTERACTION WITH PDLIM4, AND INDUCTION.
RX PubMed=21636573; DOI=10.1074/jbc.m111.241554;
RA Guryanova O.A., Drazba J.A., Frolova E.I., Chumakov P.M.;
RT "Actin cytoskeleton remodeling by the alternatively spliced isoform of
RT PDLIM4/RIL protein.";
RL J. Biol. Chem. 286:26849-26859(2011).
RN [14]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-82, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=23186163; DOI=10.1021/pr300630k;
RA Zhou H., Di Palma S., Preisinger C., Peng M., Polat A.N., Heck A.J.,
RA Mohammed S.;
RT "Toward a comprehensive characterization of a human cancer cell
RT phosphoproteome.";
RL J. Proteome Res. 12:260-271(2013).
RN [15]
RP SUMOYLATION [LARGE SCALE ANALYSIS] AT LYS-250 AND LYS-251, AND
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=28112733; DOI=10.1038/nsmb.3366;
RA Hendriks I.A., Lyon D., Young C., Jensen L.J., Vertegaal A.C.,
RA Nielsen M.L.;
RT "Site-specific mapping of the human SUMO proteome reveals co-modification
RT with phosphorylation.";
RL Nat. Struct. Mol. Biol. 24:325-336(2017).
RN [16]
RP FUNCTION, COFACTOR, SUBUNIT, INTERACTION WITH TP73, REGION, AND
RP CHARACTERIZATION OF VARIANT SER-187.
RX PubMed=28291250; DOI=10.1038/srep44532;
RA Medina-Carmona E., Neira J.L., Salido E., Fuchs J.E., Palomino-Morales R.,
RA Timson D.J., Pey A.L.;
RT "Site-to-site interdomain communication may mediate different loss-of-
RT function mechanisms in a cancer-associated NQO1 polymorphism.";
RL Sci. Rep. 7:44532-44532(2017).
RN [17]
RP X-RAY CRYSTALLOGRAPHY (2.3 ANGSTROMS) OF 4-274 IN COMPLEX WITH FAD, AND
RP SUBUNIT.
RX PubMed=10543876; DOI=10.1021/jm991060m;
RA Skelly J.V., Sanderson M.R., Suter D.A., Baumann U., Read M.A.,
RA Gregory D.S.J., Bennett M., Hobbs S.M., Neidle S.;
RT "Crystal structure of human DT-diaphorase: a model for interaction with the
RT cytotoxic prodrug 5-(aziridin-1-yl)-2,4-dinitrobenzamide (CB1954).";
RL J. Med. Chem. 42:4325-4330(1999).
RN [18]
RP X-RAY CRYSTALLOGRAPHY (1.7 ANGSTROMS) IN COMPLEX WITH FAD AND DUROQUINONE.
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).
RN [19]
RP X-RAY CRYSTALLOGRAPHY (1.8 ANGSTROMS) IN COMPLEX WITH FAD AND THE INHIBITOR
RP ES936, AND MASS SPECTROMETRY.
RX PubMed=11735396; DOI=10.1021/bi011324i;
RA Winski S.L., Faig M., Bianchet M.A., Siegel D., Swann E., Fung K.,
RA Duncan M.W., Moody C.J., Amzel L.M., Ross D.;
RT "Characterization of a mechanism-based inhibitor of NAD(P)H:quinone
RT oxidoreductase 1 by biochemical, X-ray crystallographic, and mass
RT spectrometric approaches.";
RL Biochemistry 40:15135-15142(2001).
RN [20]
RP X-RAY CRYSTALLOGRAPHY (1.7 ANGSTROMS) IN COMPLEXES WITH FAD AND INHIBITORS,
RP AND SUBUNIT.
RX PubMed=11587640; DOI=10.1016/s0969-2126(01)00636-0;
RA Faig M., Bianchet M.A., Winski S., Hargreaves R., Moody C.J., Hudnott A.R.,
RA Ross D., Amzel L.M.;
RT "Structure-based development of anticancer drugs: complexes of
RT NAD(P)H:quinone oxidoreductase 1 with chemotherapeutic quinones.";
RL Structure 9:659-667(2001).
RN [21]
RP X-RAY CRYSTALLOGRAPHY (2.75 ANGSTROMS) IN COMPLEX WITH THE INHIBITOR
RP DICOUMAROL.
RX PubMed=16700548; DOI=10.1021/bi0600087;
RA Asher G., Dym O., Tsvetkov P., Adler J., Shaul Y.;
RT "The crystal structure of NAD(P)H quinone oxidoreductase 1 in complex with
RT its potent inhibitor dicoumarol.";
RL Biochemistry 45:6372-6378(2006).
RN [22]
RP VARIANT SER-187.
RX PubMed=1737339;
RA Traver R.D., Horikoshi T., Danenberg K.D., Stadlbauer T.H., Danenberg P.V.,
RA Ross D., Gibson N.W.;
RT "NAD(P)H:quinone oxidoreductase gene expression in human colon carcinoma
RT cells: characterization of a mutation which modulates DT-diaphorase
RT activity and mitomycin sensitivity.";
RL Cancer Res. 52:797-802(1992).
RN [23]
RP VARIANT SER-187.
RX PubMed=10447260;
RX DOI=10.1002/(sici)1098-1004(1999)14:1<67::aid-humu8>3.0.co;2-5;
RA Kristiansen O.P., Larsen Z.M., Johannesen J., Nerup J., Mandrup-Poulsen T.,
RA Pociot F.;
RT "No linkage of P187S polymorphism in NAD(P)H: quinone oxidoreductase
RT (NQO1/DIA4) and type 1 diabetes in the Danish population.";
RL Hum. Mutat. 14:67-70(1999).
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,
CC PubMed:9271353) (By similarity). Regulates cellular redox state
CC primarily through quinone detoxification. Reduces components of plasma
CC membrane redox system such as coenzyme Q and vitamin quinones,
CC producing antioxidant hydroquinone forms. In the process may function
CC as superoxide scavenger to prevent hydroquinone oxidation and
CC facilitate excretion (PubMed:8999809, PubMed:9271353, PubMed:15102952).
CC Alternatively, can activate quinones and their derivatives by
CC generating redox reactive hydroquinones with DNA cross-linking
CC antitumor potential (PubMed:8999809). 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 (PubMed:15687255, PubMed:28291250).
CC {ECO:0000250|UniProtKB:P05982, ECO:0000269|PubMed:15102952,
CC ECO:0000269|PubMed:15687255, ECO:0000269|PubMed:28291250,
CC ECO:0000269|PubMed:8999809, ECO:0000269|PubMed:9271353}.
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, ECO:0000269|PubMed:9271353};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:46161;
CC Evidence={ECO:0000305|PubMed:8999809, ECO:0000305|PubMed:9271353};
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:0000269|PubMed:9271353};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:46165;
CC Evidence={ECO:0000305|PubMed:9271353};
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:0000269|PubMed:9271353};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:61985;
CC Evidence={ECO:0000305|PubMed:9271353};
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:0000269|PubMed:28291250};
CC -!- ACTIVITY REGULATION: Inhibited by dicoumarol.
CC {ECO:0000269|PubMed:15687255, ECO:0000269|PubMed:9271353}.
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC Kinetic parameters:
CC KM=2.7 uM for menadione {ECO:0000269|PubMed:8999809};
CC KM=220 uM for NADH {ECO:0000269|PubMed:8999809};
CC KM=1370 uM for 5-(aziridin-1-yl)-2,4-dinitrobenzamide
CC {ECO:0000269|PubMed:8999809};
CC Vmax=1100 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:10543876, PubMed:10706635, PubMed:11735396,
CC PubMed:11587640, PubMed:16700548, PubMed:28291250). Interacts with
CC PDLIM4 isoform 2; this interaction stabilizes PDLIM4 isoform 2 in
CC response to oxidative stress and protects it from ubiquitin-independent
CC degradation by the core 20S proteasome (PubMed:21636573). Interacts
CC with TP73 (via SAM domain); this interaction is NADH-dependent,
CC stabilizes TP73 in response to oxidative stress and protects it from
CC ubiquitin-independent degradation by the 20S proteasome
CC (PubMed:28291250, PubMed:15687255). Interacts with TP53; this
CC interaction is NADH-dependent, stabilizes TP53 in response to oxidative
CC stress and protects it from ubiquitin-independent degradation by the
CC 20S proteasome (PubMed:15687255). {ECO:0000269|PubMed:10543876,
CC ECO:0000269|PubMed:10706635, ECO:0000269|PubMed:11587640,
CC ECO:0000269|PubMed:11735396, ECO:0000269|PubMed:15687255,
CC ECO:0000269|PubMed:16700548, ECO:0000269|PubMed:21636573,
CC ECO:0000269|PubMed:28291250}.
CC -!- INTERACTION:
CC P15559; P07902: GALT; NbExp=3; IntAct=EBI-3989435, EBI-750827;
CC P15559; Q9UK53: ING1; NbExp=3; IntAct=EBI-3989435, EBI-399198;
CC P15559; P15559: NQO1; NbExp=5; IntAct=EBI-3989435, EBI-3989435;
CC -!- SUBCELLULAR LOCATION: Cytoplasm, cytosol
CC {ECO:0000250|UniProtKB:P05982}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=3;
CC Name=1;
CC IsoId=P15559-1; Sequence=Displayed;
CC Name=2;
CC IsoId=P15559-2; Sequence=VSP_042716;
CC Name=3;
CC IsoId=P15559-3; Sequence=VSP_044446;
CC -!- INDUCTION: By dioxin (PubMed:1657151). By oxidative stress
CC (PubMed:21636573). {ECO:0000269|PubMed:1657151,
CC ECO:0000269|PubMed:21636573}.
CC -!- MASS SPECTROMETRY: Mass=30864; Mass_error=6; Method=Electrospray;
CC Evidence={ECO:0000269|PubMed:11735396};
CC -!- POLYMORPHISM: The Ser-187 polymorphism may be linked to susceptibility
CC to forms of cancers.
CC -!- MISCELLANEOUS: Quinone reductase accepts electrons from both NADH and
CC NADPH with equal efficiency.
CC -!- SIMILARITY: Belongs to the NAD(P)H dehydrogenase (quinone) family.
CC {ECO:0000305}.
CC -!- WEB RESOURCE: Name=Atlas of Genetics and Cytogenetics in Oncology and
CC Haematology;
CC URL="http://atlasgeneticsoncology.org/Genes/NQO1ID375.html";
CC -!- WEB RESOURCE: Name=NIEHS-SNPs;
CC URL="http://egp.gs.washington.edu/data/nqo1/";
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DR EMBL; J03934; AAA59940.1; -; mRNA.
DR EMBL; M81600; AAB60701.1; -; Genomic_DNA.
DR EMBL; M81596; AAB60701.1; JOINED; Genomic_DNA.
DR EMBL; M81597; AAB60701.1; JOINED; Genomic_DNA.
DR EMBL; M81598; AAB60701.1; JOINED; Genomic_DNA.
DR EMBL; M81599; AAB60701.1; JOINED; Genomic_DNA.
DR EMBL; AY281093; AAP20940.1; ALT_SEQ; Genomic_DNA.
DR EMBL; AK297979; BAG60289.1; -; mRNA.
DR EMBL; AK312368; BAG35286.1; -; mRNA.
DR EMBL; AK316246; BAH14617.1; -; mRNA.
DR EMBL; AC092115; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CH471092; EAW83283.1; -; Genomic_DNA.
DR EMBL; CH471092; EAW83284.1; -; Genomic_DNA.
DR EMBL; BC007659; AAH07659.1; -; mRNA.
DR CCDS; CCDS10883.1; -. [P15559-1]
DR CCDS; CCDS32471.1; -. [P15559-3]
DR CCDS; CCDS32472.1; -. [P15559-2]
DR PIR; A41135; A30879.
DR RefSeq; NP_000894.1; NM_000903.2. [P15559-1]
DR RefSeq; NP_001020604.1; NM_001025433.1. [P15559-2]
DR RefSeq; NP_001020605.1; NM_001025434.1. [P15559-3]
DR PDB; 1D4A; X-ray; 1.70 A; A/B/C/D=2-274.
DR PDB; 1DXO; X-ray; 2.50 A; A/B/C/D=2-274.
DR PDB; 1GG5; X-ray; 2.50 A; A/B/C/D=2-274.
DR PDB; 1H66; X-ray; 2.00 A; A/B/C/D=3-274.
DR PDB; 1H69; X-ray; 1.86 A; A/B/C/D=3-274.
DR PDB; 1KBO; X-ray; 2.30 A; A/B/C/D=2-274.
DR PDB; 1KBQ; X-ray; 1.80 A; A/B/C/D=2-274.
DR PDB; 1QBG; X-ray; 2.30 A; A/B/C/D=4-274.
DR PDB; 2F1O; X-ray; 2.75 A; A/B/C/D/E/F/G/H=2-274.
DR PDB; 3JSX; X-ray; 2.45 A; A/B/C/D/E/F/G/H=2-274.
DR PDB; 4CET; X-ray; 2.20 A; A=1-274.
DR PDB; 4CF6; X-ray; 2.69 A; A/B=1-274.
DR PDB; 5A4K; X-ray; 2.09 A; A/B/C/D=1-274.
DR PDB; 5EA2; X-ray; 2.01 A; A/C/E/G=1-273.
DR PDB; 5EAI; X-ray; 2.90 A; A/B/C/D/E/F/G/H/I/J/K/L/M/N=1-274.
DR PDB; 5FUQ; X-ray; 2.04 A; A/B=1-274.
DR PDB; 6FY4; X-ray; 2.76 A; A/B/C/D=1-274.
DR PDB; 6LLC; X-ray; 2.50 A; A/B/C/D/E/F/G/H/I/J/K/L=2-274.
DR PDBsum; 1D4A; -.
DR PDBsum; 1DXO; -.
DR PDBsum; 1GG5; -.
DR PDBsum; 1H66; -.
DR PDBsum; 1H69; -.
DR PDBsum; 1KBO; -.
DR PDBsum; 1KBQ; -.
DR PDBsum; 1QBG; -.
DR PDBsum; 2F1O; -.
DR PDBsum; 3JSX; -.
DR PDBsum; 4CET; -.
DR PDBsum; 4CF6; -.
DR PDBsum; 5A4K; -.
DR PDBsum; 5EA2; -.
DR PDBsum; 5EAI; -.
DR PDBsum; 5FUQ; -.
DR PDBsum; 6FY4; -.
DR PDBsum; 6LLC; -.
DR AlphaFoldDB; P15559; -.
DR SMR; P15559; -.
DR BioGRID; 108072; 61.
DR DIP; DIP-24210N; -.
DR IntAct; P15559; 9.
DR MINT; P15559; -.
DR STRING; 9606.ENSP00000319788; -.
DR BindingDB; P15559; -.
DR ChEMBL; CHEMBL3623; -.
DR DrugBank; DB07385; 3-(HYDROXYMETHYL)-1-METHYL-5-(2-METHYLAZIRIDIN-1-YL)-2-PHENYL-1H-INDOLE-4,7-DIONE.
DR DrugBank; DB02395; 3-Hydroxymethyl-5-Aziridinyl-1methyl-2-[1h-Indole-4,7-Dione]-Propanol.
DR DrugBank; DB03626; 5-Methoxy-1,2-Dimethyl-3-(Phenoxymethyl)Indole-4,7-Dione.
DR DrugBank; DB14001; alpha-Tocopherol succinate.
DR DrugBank; DB04392; Bishydroxy[2h-1-Benzopyran-2-One,1,2-Benzopyrone].
DR DrugBank; DB09061; Cannabidiol.
DR DrugBank; DB00958; Carboplatin.
DR DrugBank; DB02633; Cibacron Blue.
DR DrugBank; DB00515; Cisplatin.
DR DrugBank; DB14002; D-alpha-Tocopherol acetate.
DR DrugBank; DB00266; Dicoumarol.
DR DrugBank; DB00997; Doxorubicin.
DR DrugBank; DB01927; Duroquinone.
DR DrugBank; DB02400; ES-936.
DR DrugBank; DB03147; Flavin adenine dinucleotide.
DR DrugBank; DB00170; Menadione.
DR DrugBank; DB00526; Oxaliplatin.
DR DrugBank; DB00252; Phenytoin.
DR DrugBank; DB04090; RH-1.
DR DrugBank; DB00163; Vitamin E.
DR DrugCentral; P15559; -.
DR iPTMnet; P15559; -.
DR MetOSite; P15559; -.
DR PhosphoSitePlus; P15559; -.
DR SwissPalm; P15559; -.
DR BioMuta; NQO1; -.
DR DMDM; 118607; -.
DR EPD; P15559; -.
DR jPOST; P15559; -.
DR MassIVE; P15559; -.
DR MaxQB; P15559; -.
DR PaxDb; P15559; -.
DR PeptideAtlas; P15559; -.
DR PRIDE; P15559; -.
DR ProteomicsDB; 53187; -. [P15559-1]
DR ProteomicsDB; 53188; -. [P15559-2]
DR TopDownProteomics; P15559-1; -. [P15559-1]
DR Antibodypedia; 1549; 823 antibodies from 43 providers.
DR DNASU; 1728; -.
DR Ensembl; ENST00000320623.10; ENSP00000319788.5; ENSG00000181019.13. [P15559-1]
DR Ensembl; ENST00000379046.6; ENSP00000368334.2; ENSG00000181019.13. [P15559-3]
DR Ensembl; ENST00000379047.7; ENSP00000368335.3; ENSG00000181019.13. [P15559-2]
DR GeneID; 1728; -.
DR KEGG; hsa:1728; -.
DR MANE-Select; ENST00000320623.10; ENSP00000319788.5; NM_000903.3; NP_000894.1.
DR UCSC; uc002exp.5; human. [P15559-1]
DR CTD; 1728; -.
DR DisGeNET; 1728; -.
DR GeneCards; NQO1; -.
DR HGNC; HGNC:2874; NQO1.
DR HPA; ENSG00000181019; Tissue enhanced (stomach).
DR MIM; 125860; gene.
DR neXtProt; NX_P15559; -.
DR OpenTargets; ENSG00000181019; -.
DR PharmGKB; PA31744; -.
DR VEuPathDB; HostDB:ENSG00000181019; -.
DR eggNOG; ENOG502QQMI; Eukaryota.
DR GeneTree; ENSGT00940000159150; -.
DR InParanoid; P15559; -.
DR OMA; WFERVLV; -.
DR OrthoDB; 1394543at2759; -.
DR PhylomeDB; P15559; -.
DR TreeFam; TF300296; -.
DR BioCyc; MetaCyc:HS11566-MON; -.
DR BRENDA; 1.6.5.2; 2681.
DR PathwayCommons; P15559; -.
DR Reactome; R-HSA-350562; Regulation of ornithine decarboxylase (ODC).
DR Reactome; R-HSA-9759194; Nuclear events mediated by NFE2L2.
DR SABIO-RK; P15559; -.
DR SignaLink; P15559; -.
DR SIGNOR; P15559; -.
DR BioGRID-ORCS; 1728; 18 hits in 1082 CRISPR screens.
DR ChiTaRS; NQO1; human.
DR EvolutionaryTrace; P15559; -.
DR GeneWiki; NAD(P)H_dehydrogenase_(quinone_1); -.
DR GenomeRNAi; 1728; -.
DR Pharos; P15559; Tchem.
DR PRO; PR:P15559; -.
DR Proteomes; UP000005640; Chromosome 16.
DR RNAct; P15559; protein.
DR Bgee; ENSG00000181019; Expressed in endometrium epithelium and 201 other tissues.
DR ExpressionAtlas; P15559; baseline and differential.
DR Genevisible; P15559; HS.
DR GO; GO:0005737; C:cytoplasm; TAS:ProtInc.
DR GO; GO:0005829; C:cytosol; IDA:CAFA.
DR GO; GO:0030425; C:dendrite; IEA:Ensembl.
DR GO; GO:0043025; C:neuronal cell body; IEA:Ensembl.
DR GO; GO:0045202; C:synapse; IEA:GOC.
DR GO; GO:0004128; F:cytochrome-b5 reductase activity, acting on NAD(P)H; TAS:ProtInc.
DR GO; GO:0042802; F:identical protein binding; IPI:IntAct.
DR GO; GO:0003955; F:NAD(P)H dehydrogenase (quinone) activity; IBA:GO_Central.
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:0003723; F:RNA binding; HDA:UniProtKB.
DR GO; GO:0004784; F:superoxide dismutase activity; IEA:Ensembl.
DR GO; GO:0007568; P:aging; IEA:Ensembl.
DR GO; GO:0045454; P:cell redox homeostasis; IEP:UniProtKB.
DR GO; GO:0070301; P:cellular response to hydrogen peroxide; IEA:Ensembl.
DR GO; GO:0071248; P:cellular response to metal ion; IEA:Ensembl.
DR GO; GO:0034599; P:cellular response to oxidative stress; IDA:UniProtKB.
DR GO; GO:0006116; P:NADH oxidation; IEA:Ensembl.
DR GO; GO:0070995; P:NADPH oxidation; IEA:Ensembl.
DR GO; GO:0043066; P:negative regulation of apoptotic process; IEA:Ensembl.
DR GO; GO:0043086; P:negative regulation of catalytic activity; IEA:Ensembl.
DR GO; GO:0042177; P:negative regulation of protein catabolic process; IDA:UniProtKB.
DR GO; GO:0006809; P:nitric oxide biosynthetic process; TAS:ProtInc.
DR GO; GO:0043525; P:positive regulation of neuron apoptotic process; IEA:Ensembl.
DR GO; GO:0019430; P:removal of superoxide radicals; IDA:UniProtKB.
DR GO; GO:0043279; P:response to alkaloid; IEA:Ensembl.
DR GO; GO:0014075; P:response to amine; IEA:Ensembl.
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; IEA:Ensembl.
DR GO; GO:0007584; P:response to nutrient; IEA:Ensembl.
DR GO; GO:0006979; P:response to oxidative stress; IEP:UniProtKB.
DR GO; GO:0033574; P:response to testosterone; IEA:Ensembl.
DR GO; GO:1904772; P:response to tetrachloromethane; IEA:Ensembl.
DR GO; GO:0009636; P:response to toxic substance; TAS:ProtInc.
DR GO; GO:0007271; P:synaptic transmission, cholinergic; TAS:ProtInc.
DR GO; GO:0006743; P:ubiquinone metabolic process; IDA:UniProtKB.
DR GO; GO:0042360; P:vitamin E metabolic process; IDA:UniProtKB.
DR GO; GO:0042373; P:vitamin K metabolic process; IDA:UniProtKB.
DR GO; GO:0006805; P:xenobiotic metabolic process; TAS:ProtInc.
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; Alternative splicing; Cytoplasm; FAD; Flavoprotein;
KW Isopeptide bond; NAD; NADP; Oxidoreductase; Phosphoprotein;
KW Reference proteome; Ubl conjugation.
FT CHAIN 1..274
FT /note="NAD(P)H dehydrogenase [quinone] 1"
FT /id="PRO_0000071622"
FT REGION 225..274
FT /note="Important for apoenzyme conformational stability"
FT /evidence="ECO:0000269|PubMed:28291250"
FT BINDING 12
FT /ligand="FAD"
FT /ligand_id="ChEBI:CHEBI:57692"
FT /evidence="ECO:0000269|PubMed:10543876,
FT ECO:0000269|PubMed:10706635, ECO:0000269|PubMed:11735396"
FT BINDING 18..19
FT /ligand="FAD"
FT /ligand_id="ChEBI:CHEBI:57692"
FT /evidence="ECO:0000269|PubMed:10543876,
FT ECO:0000269|PubMed:10706635, ECO:0000269|PubMed:11735396"
FT BINDING 67
FT /ligand="FAD"
FT /ligand_id="ChEBI:CHEBI:57692"
FT /evidence="ECO:0000269|PubMed:10543876,
FT ECO:0000269|PubMed:10706635, ECO:0000269|PubMed:11735396"
FT BINDING 104..107
FT /ligand="FAD"
FT /ligand_id="ChEBI:CHEBI:57692"
FT /evidence="ECO:0000269|PubMed:10543876,
FT ECO:0000269|PubMed:10706635, ECO:0000269|PubMed:11735396"
FT BINDING 126..128
FT /ligand="substrate"
FT BINDING 148..151
FT /ligand="FAD"
FT /ligand_id="ChEBI:CHEBI:57692"
FT /evidence="ECO:0000269|PubMed:10543876,
FT ECO:0000269|PubMed:10706635, ECO:0000269|PubMed:11735396"
FT BINDING 156
FT /ligand="FAD"
FT /ligand_id="ChEBI:CHEBI:57692"
FT /evidence="ECO:0000269|PubMed:10543876,
FT ECO:0000269|PubMed:10706635, ECO:0000269|PubMed:11735396"
FT BINDING 201
FT /ligand="FAD"
FT /ligand_id="ChEBI:CHEBI:57692"
FT /evidence="ECO:0000269|PubMed:10543876,
FT ECO:0000269|PubMed:10706635, ECO:0000269|PubMed:11735396"
FT MOD_RES 82
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:23186163"
FT CROSSLNK 250
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO2)"
FT /evidence="ECO:0007744|PubMed:28112733"
FT CROSSLNK 251
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO2)"
FT /evidence="ECO:0007744|PubMed:28112733"
FT VAR_SEQ 102..139
FT /note="Missing (in isoform 3)"
FT /evidence="ECO:0000303|PubMed:14702039"
FT /id="VSP_044446"
FT VAR_SEQ 140..173
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:14702039"
FT /id="VSP_042716"
FT VARIANT 139
FT /note="R -> W (in dbSNP:rs1131341)"
FT /id="VAR_016170"
FT VARIANT 187
FT /note="P -> S (loss of function associated with defective
FT cofactor binding and accelerated proteosomal degradation;
FT dbSNP:rs1800566)"
FT /evidence="ECO:0000269|PubMed:10447260,
FT ECO:0000269|PubMed:14702039, ECO:0000269|PubMed:1737339,
FT ECO:0000269|PubMed:28291250, ECO:0000269|Ref.3"
FT /id="VAR_008384"
FT VARIANT 269
FT /note="Q -> H (in dbSNP:rs34447156)"
FT /id="VAR_050220"
FT MUTAGEN 105
FT /note="Q->Y: Decreases the catalytic efficiency toward
FT menadione. Increases the affinity toward NADH. Increases
FT the catalytic afficiency toward nitrobenzene substrate. Has
FT no effect on the affinity toward NADH; when associated with
FT V-204."
FT /evidence="ECO:0000269|PubMed:8999809"
FT MUTAGEN 129
FT /note="Y->F,V: Abolishes the interaction with TP73."
FT /evidence="ECO:0000269|PubMed:15687255"
FT MUTAGEN 204
FT /note="I->V: Has no effect on the affinity toward NADH;
FT when associated with Y-105."
FT /evidence="ECO:0000269|PubMed:8999809"
FT CONFLICT 252
FT /note="F -> S (in Ref. 4; BAG60289)"
FT /evidence="ECO:0000305"
FT STRAND 5..10
FT /evidence="ECO:0007829|PDB:1D4A"
FT STRAND 15..17
FT /evidence="ECO:0007829|PDB:1QBG"
FT HELIX 18..32
FT /evidence="ECO:0007829|PDB:1D4A"
FT STRAND 36..41
FT /evidence="ECO:0007829|PDB:1D4A"
FT TURN 42..46
FT /evidence="ECO:0007829|PDB:1D4A"
FT HELIX 53..55
FT /evidence="ECO:0007829|PDB:1D4A"
FT STRAND 56..58
FT /evidence="ECO:0007829|PDB:5EA2"
FT HELIX 63..65
FT /evidence="ECO:0007829|PDB:5EA2"
FT HELIX 68..78
FT /evidence="ECO:0007829|PDB:1D4A"
FT HELIX 83..94
FT /evidence="ECO:0007829|PDB:1D4A"
FT STRAND 96..103
FT /evidence="ECO:0007829|PDB:1D4A"
FT STRAND 106..108
FT /evidence="ECO:0007829|PDB:4CET"
FT HELIX 111..120
FT /evidence="ECO:0007829|PDB:1D4A"
FT TURN 124..126
FT /evidence="ECO:0007829|PDB:1D4A"
FT HELIX 129..131
FT /evidence="ECO:0007829|PDB:1H69"
FT HELIX 133..135
FT /evidence="ECO:0007829|PDB:1D4A"
FT TURN 137..140
FT /evidence="ECO:0007829|PDB:1D4A"
FT STRAND 142..148
FT /evidence="ECO:0007829|PDB:1D4A"
FT HELIX 154..156
FT /evidence="ECO:0007829|PDB:1D4A"
FT STRAND 160..162
FT /evidence="ECO:0007829|PDB:1H69"
FT HELIX 165..173
FT /evidence="ECO:0007829|PDB:1D4A"
FT TURN 174..177
FT /evidence="ECO:0007829|PDB:1D4A"
FT HELIX 178..180
FT /evidence="ECO:0007829|PDB:1D4A"
FT STRAND 188..190
FT /evidence="ECO:0007829|PDB:1D4A"
FT HELIX 193..195
FT /evidence="ECO:0007829|PDB:1D4A"
FT HELIX 198..212
FT /evidence="ECO:0007829|PDB:1D4A"
FT HELIX 213..217
FT /evidence="ECO:0007829|PDB:1D4A"
FT HELIX 226..228
FT /evidence="ECO:0007829|PDB:1D4A"
FT HELIX 233..235
FT /evidence="ECO:0007829|PDB:1D4A"
FT STRAND 237..239
FT /evidence="ECO:0007829|PDB:1H69"
FT HELIX 241..248
FT /evidence="ECO:0007829|PDB:1D4A"
FT STRAND 254..256
FT /evidence="ECO:0007829|PDB:1D4A"
FT TURN 266..270
FT /evidence="ECO:0007829|PDB:1D4A"
SQ SEQUENCE 274 AA; 30868 MW; A4010462AD00F3FE CRC64;
MVGRRALIVL AHSERTSFNY AMKEAAAAAL KKKGWEVVES DLYAMNFNPI ISRKDITGKL
KDPANFQYPA ESVLAYKEGH LSPDIVAEQK KLEAADLVIF QFPLQWFGVP AILKGWFERV
FIGEFAYTYA AMYDKGPFRS KKAVLSITTG GSGSMYSLQG IHGDMNVILW PIQSGILHFC
GFQVLEPQLT YSIGHTPADA RIQILEGWKK RLENIWDETP LYFAPSSLFD LNFQAGFLMK
KEVQDEEKNK KFGLSVGHHL GKSIPTDNQI KARK
