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
- FunctionsNADH / NADPH dehydrogenase (quinone) activity / RNA bindingProcessescell 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 processComponentsdendrite / 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
- Flavodoxin_2 (PF02525)
- 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
Resource Link UniProtKB ID P15559 UniProtKB Entry Name NQO1_HUMAN GenBank Protein ID 189246 GenBank Gene ID J03934 GeneCard ID NQO1 GenAtlas ID NQO1 HGNC ID HGNC: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 ID hsa:1728 NCBI Gene ID 1728 - General References
- 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]
- Jaiswal AK: Human NAD(P)H:quinone oxidoreductase (NQO1) gene structure and induction by dioxin. Biochemistry. 1991 Nov 5;30(44):10647-53. [Article]
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- 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]
- 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]
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- 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]
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Associated Data
- Bio-Entities
Bio-Entity Type NAD(P)H dehydrogenase [quinone] 1 (Humans) protein primary- Drug Relations
Drug Drug group Pharmacological action? Type Actions Details Dicoumarol approved unknown target inhibitor Details Duroquinone experimental yes target inhibitor Details 3-Hydroxymethyl-5-Aziridinyl-1methyl-2-[1h-Indole-4,7-Dione]-Propanol experimental unknown target Details ES-936 experimental yes target inhibitor Details Cibacron Blue experimental unknown target Details Flavin adenine dinucleotide approved yes target inhibitor Details 5-Methoxy-1,2-Dimethyl-3-(Phenoxymethyl)Indole-4,7-Dione experimental unknown target Details RH-1 experimental, investigational unknown target Details Menadione approved, nutraceutical unknown target Details 3-(HYDROXYMETHYL)-1-METHYL-5-(2-METHYLAZIRIDIN-1-YL)-2-PHENYL-1H-INDOLE-4,7-DIONE experimental unknown target Details Bishydroxy[2h-1-Benzopyran-2-One,1,2-Benzopyrone] experimental yes target inhibitor Details Vitamin E approved, nutraceutical, vet_approved unknown enzyme inducer Details Doxorubicin approved, investigational no enzyme substrate Details Cisplatin approved unknown enzyme substrate Details Carboplatin approved unknown enzyme substrate Details Oxaliplatin approved, investigational no enzyme substrate Details alpha-Tocopherol succinate approved, nutraceutical, vet_approved unknown enzyme inducer Details D-alpha-Tocopherol acetate approved, nutraceutical, vet_approved unknown enzyme inducer Details Cannabidiol approved, investigational unknown target inhibitor Details Phenytoin approved, vet_approved no enzyme substrate Details