NAD(P)H dehydrogenase [quinone] 1

Details

Name
NAD(P)H dehydrogenase [quinone] 1
Synonyms
  • 1.6.5.2
  • Azoreductase
  • DIA4
  • DT-diaphorase
  • DTD
  • Menadione reductase
  • NAD(P)H:quinone oxidoreductase 1
  • NMOR1
  • Phylloquinone reductase
  • QR1
  • Quinone reductase 1
Gene Name
NQO1
UniProtKB Entry
P15559Swiss-Prot
Organism
Humans
NCBI Taxonomy ID
9606
Amino acid sequence
>lcl|BSEQ0002355|NAD(P)H dehydrogenase [quinone] 1
MVGRRALIVLAHSERTSFNYAMKEAAAAALKKKGWEVVESDLYAMNFNPIISRKDITGKL
KDPANFQYPAESVLAYKEGHLSPDIVAEQKKLEAADLVIFQFPLQWFGVPAILKGWFERV
FIGEFAYTYAAMYDKGPFRSKKAVLSITTGGSGSMYSLQGIHGDMNVILWPIQSGILHFC
GFQVLEPQLTYSIGHTPADARIQILEGWKKRLENIWDETPLYFAPSSLFDLNFQAGFLMK
KEVQDEEKNKKFGLSVGHHLGKSIPTDNQIKARK
Number of residues
274
Molecular Weight
30867.405
Theoretical pI
9.34
GO Classification
Functions
NADH / NADPH dehydrogenase (quinone) activity / RNA binding
Processes
cell redox homeostasis / cellular response to hydrogen peroxide / cellular response to metal ion / cellular response to oxidative stress / innate immune response / NADH oxidation / NADPH oxidation / negative regulation of apoptotic process / negative regulation of ferroptosis / negative regulation of protein catabolic process / protein catabolic process / protein polyubiquitination / removal of superoxide radicals / response to alkaloid / response to amine / response to carbohydrate / response to electrical stimulus / response to flavonoid / response to hormone / response to hydrogen sulfide / response to ischemia / response to L-glutamine / response to lipopolysaccharide / response to oxidative stress / response to testosterone / response to tetrachloromethane / ubiquinone metabolic process / vitamin E metabolic process / vitamin K metabolic process
Components
dendrite / nucleus / synapse
General Function
Flavin-containing quinone reductase that catalyzes two-electron reduction of quinones to hydroquinones using either NADH or NADPH as electron donors. In a ping-pong kinetic mechanism, the electrons are sequentially transferred from NAD(P)H to flavin cofactor and then from reduced flavin to the quinone, bypassing the formation of semiquinone and reactive oxygen species (By similarity) (PubMed:8999809, PubMed:9271353). Regulates cellular redox state primarily through quinone detoxification. Reduces components of plasma membrane redox system such as coenzyme Q and vitamin quinones, producing antioxidant hydroquinone forms. In the process may function as superoxide scavenger to prevent hydroquinone oxidation and facilitate excretion (PubMed:15102952, PubMed:8999809, PubMed:9271353). Alternatively, can activate quinones and their derivatives by generating redox reactive hydroquinones with DNA cross-linking antitumor potential (PubMed:8999809). Acts as a gatekeeper of the core 20S proteasome known to degrade proteins with unstructured regions. Upon oxidative stress, interacts with tumor suppressors TP53 and TP73 in a NADH-dependent way and inhibits their ubiquitin-independent degradation by the 20S proteasome (PubMed:15687255, PubMed:28291250)
Specific Function
cytochrome-b5 reductase activity, acting on NAD(P)H
Pfam Domain Function
Signal Regions
Not Available
Transmembrane Regions
Not Available
Cellular Location
Cytoplasm, cytosol
Gene sequence
>lcl|BSEQ0016341|NAD(P)H dehydrogenase [quinone] 1 (NQO1)
ATGGTCGGCAGAAGAGCACTGATCGTACTGGCTCACTCAGAGAGGACGTCCTTCAACTAT
GCCATGAAGGAGGCTGCTGCAGCGGCTTTGAAGAAGAAAGGATGGGAGGTGGTGGAGTCG
GACCTCTATGCCATGAACTTCAATCCCATCATTTCCAGAAAGGACATCACAGGTAAACTG
AAGGACCCTGCGAACTTTCAGTATCCTGCCGAGTCTGTTCTGGCTTATAAAGAAGGCCAT
CTGAGCCCAGATATTGTGGCTGAACAAAAGAAGCTGGAAGCCGCAGACCTTGTGATATTC
CAGTTCCCCCTGCAGTGGTTTGGAGTCCCTGCCATTCTGAAAGGCTGGTTTGAGCGAGTG
TTCATAGGAGAGTTTGCTTACACTTACGCTGCCATGTATGACAAAGGACCCTTCCGGAGT
AAGAAGGCAGTGCTTTCCATCACCACTGGTGGCAGTGGCTCCATGTACTCTCTGCAAGGG
ATCCACGGGGACATGAATGTCATTCTCTGGCCAATTCAGAGTGGCATTCTGCATTTCTGT
GGCTTCCAAGTCTTAGAACCTCAACTGACATATAGCATTGGGCACACTCCAGCAGACGCC
CGAATTCAAATCCTGGAAGGATGGAAGAAACGCCTGGAGAATATTTGGGATGAGACACCA
CTGTATTTTGCTCCAAGCAGCCTCTTTGACCTAAACTTCCAGGCAGGATTCTTAATGAAA
AAAGAGGTACAGGATGAGGAGAAAAACAAGAAATTTGGCCTTTCTGTGGGCCATCACTTG
GGCAAGTCCATCCCAACTGACAACCAGATCAAAGCTAGAAAATGA
Chromosome Location
16
Locus
16q22.1
External Identifiers
ResourceLink
UniProtKB IDP15559
UniProtKB Entry NameNQO1_HUMAN
GenBank Protein ID189246
GenBank Gene IDJ03934
GeneCard IDNQO1
GenAtlas IDNQO1
HGNC IDHGNC:2874
PDB ID(s)1D4A, 1DXO, 1GG5, 1H66, 1H69, 1KBO, 1KBQ, 1QBG, 2F1O, 3JSX, 4CET, 4CF6, 5A4K, 5EA2, 5EAI, 5FUQ, 6FY4, 6LLC, 8C9J, 8OK0, 8PQN, 8RFM, 8RFN
KEGG IDhsa:1728
NCBI Gene ID1728
General References
  1. Jaiswal AK, McBride OW, Adesnik M, Nebert DW: Human dioxin-inducible cytosolic NAD(P)H:menadione oxidoreductase. cDNA sequence and localization of gene to chromosome 16. J Biol Chem. 1988 Sep 25;263(27):13572-8. [Article]
  2. Jaiswal AK: Human NAD(P)H:quinone oxidoreductase (NQO1) gene structure and induction by dioxin. Biochemistry. 1991 Nov 5;30(44):10647-53. [Article]
  3. Ota T, Suzuki Y, Nishikawa T, Otsuki T, Sugiyama T, Irie R, Wakamatsu A, Hayashi K, Sato H, Nagai K, Kimura K, Makita H, Sekine M, Obayashi M, Nishi T, Shibahara T, Tanaka T, Ishii S, Yamamoto J, Saito K, Kawai Y, Isono Y, Nakamura Y, Nagahari K, Murakami K, Yasuda T, Iwayanagi T, Wagatsuma M, Shiratori A, Sudo H, Hosoiri T, Kaku Y, Kodaira H, Kondo H, Sugawara M, Takahashi M, Kanda K, Yokoi T, Furuya T, Kikkawa E, Omura Y, Abe K, Kamihara K, Katsuta N, Sato K, Tanikawa M, Yamazaki M, Ninomiya K, Ishibashi T, Yamashita H, Murakawa K, Fujimori K, Tanai H, Kimata M, Watanabe M, Hiraoka S, Chiba Y, Ishida S, Ono Y, Takiguchi S, Watanabe S, Yosida M, Hotuta T, Kusano J, Kanehori K, Takahashi-Fujii A, Hara H, Tanase TO, Nomura Y, Togiya S, Komai F, Hara R, Takeuchi K, Arita M, Imose N, Musashino K, Yuuki H, Oshima A, Sasaki N, Aotsuka S, Yoshikawa Y, Matsunawa H, Ichihara T, Shiohata N, Sano S, Moriya S, Momiyama H, Satoh N, Takami S, Terashima Y, Suzuki O, Nakagawa S, Senoh A, Mizoguchi H, Goto Y, Shimizu F, Wakebe H, Hishigaki H, Watanabe T, Sugiyama A, Takemoto M, Kawakami B, Yamazaki M, Watanabe K, Kumagai A, Itakura S, Fukuzumi Y, Fujimori Y, Komiyama M, Tashiro H, Tanigami A, Fujiwara T, Ono T, Yamada K, Fujii Y, Ozaki K, Hirao M, Ohmori Y, Kawabata A, Hikiji T, Kobatake N, Inagaki H, Ikema Y, Okamoto S, Okitani R, Kawakami T, Noguchi S, Itoh T, Shigeta K, Senba T, Matsumura K, Nakajima Y, Mizuno T, Morinaga M, Sasaki M, Togashi T, Oyama M, Hata H, Watanabe M, Komatsu T, Mizushima-Sugano J, Satoh T, Shirai Y, Takahashi Y, Nakagawa K, Okumura K, Nagase T, Nomura N, Kikuchi H, Masuho Y, Yamashita R, Nakai K, Yada T, Nakamura Y, Ohara O, Isogai T, Sugano S: Complete sequencing and characterization of 21,243 full-length human cDNAs. Nat Genet. 2004 Jan;36(1):40-5. Epub 2003 Dec 21. [Article]
  4. Martin J, Han C, Gordon LA, Terry A, Prabhakar S, She X, Xie G, Hellsten U, Chan YM, Altherr M, Couronne O, Aerts A, Bajorek E, Black S, Blumer H, Branscomb E, Brown NC, Bruno WJ, Buckingham JM, Callen DF, Campbell CS, Campbell ML, Campbell EW, Caoile C, Challacombe JF, Chasteen LA, Chertkov O, Chi HC, Christensen M, Clark LM, Cohn JD, Denys M, Detter JC, Dickson M, Dimitrijevic-Bussod M, Escobar J, Fawcett JJ, Flowers D, Fotopulos D, Glavina T, Gomez M, Gonzales E, Goodstein D, Goodwin LA, Grady DL, Grigoriev I, Groza M, Hammon N, Hawkins T, Haydu L, Hildebrand CE, Huang W, Israni S, Jett J, Jewett PB, Kadner K, Kimball H, Kobayashi A, Krawczyk MC, Leyba T, Longmire JL, Lopez F, Lou Y, Lowry S, Ludeman T, Manohar CF, Mark GA, McMurray KL, Meincke LJ, Morgan J, Moyzis RK, Mundt MO, Munk AC, Nandkeshwar RD, Pitluck S, Pollard M, Predki P, Parson-Quintana B, Ramirez L, Rash S, Retterer J, Ricke DO, Robinson DL, Rodriguez A, Salamov A, Saunders EH, Scott D, Shough T, Stallings RL, Stalvey M, Sutherland RD, Tapia R, Tesmer JG, Thayer N, Thompson LS, Tice H, Torney DC, Tran-Gyamfi M, Tsai M, Ulanovsky LE, Ustaszewska A, Vo N, White PS, Williams AL, Wills PL, Wu JR, Wu K, Yang J, Dejong P, Bruce D, Doggett NA, Deaven L, Schmutz J, Grimwood J, Richardson P, Rokhsar DS, Eichler EE, Gilna P, Lucas SM, Myers RM, Rubin EM, Pennacchio LA: The sequence and analysis of duplication-rich human chromosome 16. Nature. 2004 Dec 23;432(7020):988-94. [Article]
  5. Gerhard DS, Wagner L, Feingold EA, Shenmen CM, Grouse LH, Schuler G, Klein SL, Old S, Rasooly R, Good P, Guyer M, Peck AM, Derge JG, Lipman D, Collins FS, Jang W, Sherry S, Feolo M, Misquitta L, Lee E, Rotmistrovsky K, Greenhut SF, Schaefer CF, Buetow K, Bonner TI, Haussler D, Kent J, Kiekhaus M, Furey T, Brent M, Prange C, Schreiber K, Shapiro N, Bhat NK, Hopkins RF, Hsie F, Driscoll T, Soares MB, Casavant TL, Scheetz TE, Brown-stein MJ, Usdin TB, Toshiyuki S, Carninci P, Piao Y, Dudekula DB, Ko MS, Kawakami K, Suzuki Y, Sugano S, Gruber CE, Smith MR, Simmons B, Moore T, Waterman R, Johnson SL, Ruan Y, Wei CL, Mathavan S, Gunaratne PH, Wu J, Garcia AM, Hulyk SW, Fuh E, Yuan Y, Sneed A, Kowis C, Hodgson A, Muzny DM, McPherson J, Gibbs RA, Fahey J, Helton E, Ketteman M, Madan A, Rodrigues S, Sanchez A, Whiting M, Madari A, Young AC, Wetherby KD, Granite SJ, Kwong PN, Brinkley CP, Pearson RL, Bouffard GG, Blakesly RW, Green ED, Dickson MC, Rodriguez AC, Grimwood J, Schmutz J, Myers RM, Butterfield YS, Griffith M, Griffith OL, Krzywinski MI, Liao N, Morin R, Palmquist D, Petrescu AS, Skalska U, Smailus DE, Stott JM, Schnerch A, Schein JE, Jones SJ, Holt RA, Baross A, Marra MA, Clifton S, Makowski KA, Bosak S, Malek J: The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC). Genome Res. 2004 Oct;14(10B):2121-7. [Article]
  6. Burkard TR, Planyavsky M, Kaupe I, Breitwieser FP, Burckstummer T, Bennett KL, Superti-Furga G, Colinge J: Initial characterization of the human central proteome. BMC Syst Biol. 2011 Jan 26;5:17. doi: 10.1186/1752-0509-5-17. [Article]
  7. Skelly JV, Sanderson MR, Suter DA, Baumann U, Read MA, Gregory DS, Bennett M, Hobbs SM, Neidle S: Crystal structure of human DT-diaphorase: a model for interaction with the cytotoxic prodrug 5-(aziridin-1-yl)-2,4-dinitrobenzamide (CB1954). J Med Chem. 1999 Oct 21;42(21):4325-30. [Article]
  8. Faig M, Bianchet MA, Talalay P, Chen S, Winski S, Ross D, Amzel LM: Structures of recombinant human and mouse NAD(P)H:quinone oxidoreductases: species comparison and structural changes with substrate binding and release. Proc Natl Acad Sci U S A. 2000 Mar 28;97(7):3177-82. [Article]
  9. Winski SL, Faig M, Bianchet MA, Siegel D, Swann E, Fung K, Duncan MW, Moody CJ, Amzel LM, Ross D: Characterization of a mechanism-based inhibitor of NAD(P)H:quinone oxidoreductase 1 by biochemical, X-ray crystallographic, and mass spectrometric approaches. Biochemistry. 2001 Dec 18;40(50):15135-42. [Article]
  10. Faig M, Bianchet MA, Winski S, Hargreaves R, Moody CJ, Hudnott AR, Ross D, Amzel LM: Structure-based development of anticancer drugs: complexes of NAD(P)H:quinone oxidoreductase 1 with chemotherapeutic quinones. Structure. 2001 Aug;9(8):659-67. [Article]
  11. Asher G, Dym O, Tsvetkov P, Adler J, Shaul Y: The crystal structure of NAD(P)H quinone oxidoreductase 1 in complex with its potent inhibitor dicoumarol. Biochemistry. 2006 May 23;45(20):6372-8. [Article]
  12. Traver RD, Horikoshi T, Danenberg KD, Stadlbauer TH, Danenberg PV, Ross D, Gibson NW: NAD(P)H:quinone oxidoreductase gene expression in human colon carcinoma cells: characterization of a mutation which modulates DT-diaphorase activity and mitomycin sensitivity. Cancer Res. 1992 Feb 15;52(4):797-802. [Article]
  13. Kristiansen OP, Larsen ZM, Johannesen J, Nerup J, Mandrup-Poulsen T, Pociot F: No linkage of P187S polymorphism in NAD(P)H: quinone oxidoreductase (NQO1/DIA4) and type 1 diabetes in the Danish population. DIEGG and DSGD. Danish IDDM Epidemiology and Genetics Group and The Danish Study Group of Diabetes in Childhood. Hum Mutat. 1999;14(1):67-70. [Article]

Associated Data

Bio-Entities
Bio-EntityType
NAD(P)H dehydrogenase [quinone] 1 (Humans)protein
primary
Drug Relations
DrugDrug groupPharmacological action?TypeActionsDetails
DicoumarolapprovedunknowntargetinhibitorDetails
DuroquinoneexperimentalyestargetinhibitorDetails
3-Hydroxymethyl-5-Aziridinyl-1methyl-2-[1h-Indole-4,7-Dione]-PropanolexperimentalunknowntargetDetails
ES-936experimentalyestargetinhibitorDetails
Cibacron BlueexperimentalunknowntargetDetails
Flavin adenine dinucleotideapprovedyestargetinhibitorDetails
5-Methoxy-1,2-Dimethyl-3-(Phenoxymethyl)Indole-4,7-DioneexperimentalunknowntargetDetails
RH-1experimental, investigationalunknowntargetDetails
Menadioneapproved, nutraceuticalunknowntargetDetails
3-(HYDROXYMETHYL)-1-METHYL-5-(2-METHYLAZIRIDIN-1-YL)-2-PHENYL-1H-INDOLE-4,7-DIONEexperimentalunknowntargetDetails
Bishydroxy[2h-1-Benzopyran-2-One,1,2-Benzopyrone]experimentalyestargetinhibitorDetails
Vitamin Eapproved, nutraceutical, vet_approvedunknownenzymeinducerDetails
Doxorubicinapproved, investigationalnoenzymesubstrateDetails
CisplatinapprovedunknownenzymesubstrateDetails
CarboplatinapprovedunknownenzymesubstrateDetails
Oxaliplatinapproved, investigationalnoenzymesubstrateDetails
alpha-Tocopherol succinateapproved, nutraceutical, vet_approvedunknownenzymeinducerDetails
D-alpha-Tocopherol acetateapproved, nutraceutical, vet_approvedunknownenzymeinducerDetails
Cannabidiolapproved, investigationalunknowntargetinhibitorDetails
Phenytoinapproved, vet_approvednoenzymesubstrateDetails