NAD(P)H dehydrogenase, quinone 2

NQO2
Available structures PDB Ortholog search: PDBe RCSB List of PDB id codes 1QR2, 1SG0, 1XI2, 1ZX1, 2BZS, 2QMY, 2QMZ, 2QR2, 2QWX, 2QX4, 2QX6, 2QX8, 2QX9, 3FW1, 3G5M, 3GAM, 3NFR, 3NHF, 3NHJ, 3NHK, 3NHL, 3NHP, 3NHR, 3NHS, 3NHU, 3NHW, 3NHY, 3O2N, 3O73, 3OVM, 3OWH, 3OWX, 3OX1, 3OX2, 3OX3, 3TE7, 3TEM, 3TZB, 3UXE, 3UXH, 4FGJ, 4FGK, 4FGL, 4GQI, 4GR9, 4QOD, 4QOE, 4QOF, 4QOG, 4QOH, 4QOI, 4QOJ, 4U7F, 4U7G, 4U7H, 4XDG, 4XDH, 4ZVL, 4ZVM, 4ZVK, 5LBT, 5LBU, 5BUC, 4ZVN
Identifiers
Aliases	NQO2 , Nqo2, NMO2, Nmor2, Ox2, DHQV, DIA6, QR2, NAD(P)H quinone dehydrogenase 2, N-ribosyldihydronicotinamide:quinone reductase 2
External IDs	OMIM: 160998; MGI: 104513; HomoloGene: 696; GeneCards: NQO2; OMA:NQO2 - orthologs
Gene location (Human) Chr. Chromosome 6 (human) [1] Band 6p25.2 Start 2,987,987 bp [1] End 3,019,755 bp [1]
Gene location (Mouse) Chr. Chromosome 13 (mouse) [2] Band 13 A3.3|13 14.01 cM Start 34,148,670 bp [2] End 34,172,426 bp [2]
RNA expression pattern Bgee Human Mouse (ortholog) Top expressed in left adrenal gland left adrenal cortex right adrenal gland right adrenal cortex human kidney triceps brachii muscle right lobe of liver gastrocnemius muscle apex of heart kidney tubule Top expressed in lumbar spinal ganglion left lobe of liver granulocyte right kidney seminiferous tubule submandibular gland proximal tubule sternocleidomastoid muscle endocardial cushion lacrimal gland More reference expression data BioGPS More reference expression data
Gene ontology Molecular function protein binding metal ion binding dihydronicotinamide riboside quinone reductase activity zinc ion binding electron transfer activity oxidoreductase activity oxidoreductase activity, acting on other nitrogenous compounds as donors chloride ion binding protein homodimerization activity FAD binding melatonin binding resveratrol binding NAD(P)H dehydrogenase (quinone) activity Cellular component extracellular exosome nucleoplasm cytoplasm cytosol Biological process memory positive regulation of neuron apoptotic process positive regulation of vascular associated smooth muscle cell proliferation positive regulation of ERK1 and ERK2 cascade positive regulation of reactive oxygen species metabolic process xenobiotic metabolic process electron transport chain Sources:Amigo / QuickGO
Orthologs Species Human Mouse Entrez 4835 18105 Ensembl ENSG00000124588 ENSMUSG00000046949 UniProt P16083 Q9JI75 RefSeq (mRNA) NM_000904 NM_001290221 NM_001290222 NM_001318940 NM_001163239 NM_001163241 NM_001163242 NM_020282 RefSeq (protein) NP_000895 NP_001277150 NP_001277151 NP_001305869 NP_001156711 NP_001156713 NP_001156714 NP_064678 Location (UCSC) Chr 6: 2.99 – 3.02 Mb Chr 13: 34.15 – 34.17 Mb PubMed search [3] [4]
Wikidata
View/Edit Human View/Edit Mouse

NAD(P)H dehydrogenase, quinone 2, also known as QR2, is a protein that in humans is encoded by the NQO2 gene. It is a phase II detoxification enzyme which can carry out two or four electron reductions of quinones. Its mechanism of reduction is through a ping-pong mechanism involving its FAD cofactor. Initially in a reductive phase NQO2 binds to reduced dihydronicotinamide riboside (NRH) electron donor, and mediates a hydride transfer from NRH to FAD. Then, in an oxidative phase, NQO2 binds to its quinone substrate and reduces the quinone to a dihydroquinone. Besides the two catalytic FAD, NQO2 also has two zinc ions. It is not clear whether the metal has a catalytic role. NQO2 is a paralog of NQO1.

NQO2 is a homodimer. NQO2 can be inhibited by resveratrol. ^[5] One of QR2's binding sites responds to 2-iodomelatonin, and has been referred to as MT₃. ^[6]

References

1. GRCh38: Ensembl release 89: ENSG00000124588 – Ensembl, May 2017
2. GRCm38: Ensembl release 89: ENSMUSG00000046949 – Ensembl, May 2017
3. "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
4. "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
5. "Entrez Gene: NQO2 NAD(P)H dehydrogenase, quinone 2".
6. Cardinali DP, Delagrange P, Dubocovich ML, Jockers R, Krause DN, Markus RP, Olcese J, Pintor J, Renault N, Sugden D, Tosini G, Zlotos DP (2019). "Melatonin receptors (version 2019.4) in the IUPHAR/BPS Guide to Pharmacology Database". IUPHAR/BPS Guide to Pharmacology CITE. 2019 (4). doi: 10.2218/gtopdb/F39/2019.4 .

Further reading

• Jaiswal AK, Burnett P, Adesnik M, McBride OW (1990). "Nucleotide and deduced amino acid sequence of a human cDNA (NQO2) corresponding to a second member of the NAD(P)H:quinone oxidoreductase gene family. Extensive polymorphism at the NQO2 gene locus on chromosome 6". Biochemistry. 29 (7): 1899–906. doi:10.1021/bi00459a034. PMID   1691923.
• Jaiswal AK (1994). "Human NAD(P)H:quinone oxidoreductase2. Gene structure, activity, and tissue-specific expression". J. Biol. Chem. 269 (20): 14502–8. doi: 10.1016/S0021-9258(17)36651-6 . PMID   8182056.
• Zhao Q, Yang XL, Holtzclaw WD, Talalay P (1997). "Unexpected genetic and structural relationships of a long-forgotten flavoenzyme to NAD(P)H:quinone reductase (DT-diaphorase)". Proc. Natl. Acad. Sci. U.S.A. 94 (5): 1669–74. Bibcode:1997PNAS...94.1669Z. doi: 10.1073/pnas.94.5.1669 . PMC   19974 . PMID   9050836.
• Wu K, Knox R, Sun XZ, et al. (1997). "Catalytic properties of NAD(P)H:quinone oxidoreductase-2 (NQO2), a dihydronicotinamide riboside dependent oxidoreductase". Arch. Biochem. Biophys. 347 (2): 221–8. doi:10.1006/abbi.1997.0344. PMID   9367528.
• Foster CE, Bianchet MA, Talalay P, et al. (1999). "Crystal structure of human quinone reductase type 2, a metalloflavoprotein". Biochemistry. 38 (31): 9881–6. doi:10.1021/bi990799v. PMID   10433694.
• Jaiswal AK, Bell DW, Radjendirane V, Testa JR (1999). "Localization of human NQO1 gene to chromosome 16q22 and NQO2-6p25 and associated polymorphisms". Pharmacogenetics. 9 (3): 413–8. doi:10.1097/00008571-199906000-00020. PMID   10471077.
• Harada S, Fujii C, Hayashi A, Ohkoshi N (2001). "An association between idiopathic Parkinson's disease and polymorphisms of phase II detoxification enzymes: glutathione S-transferase M1 and quinone oxidoreductase 1 and 2". Biochem. Biophys. Res. Commun. 288 (4): 887–92. doi:10.1006/bbrc.2001.5868. PMID   11688992.
• Strassburg A, Strassburg CP, Manns MP, Tukey RH (2002). "Differential gene expression of NAD(P)H:quinone oxidoreductase and NRH:quinone oxidoreductase in human hepatocellular and biliary tissue". Mol. Pharmacol. 61 (2): 320–5. doi:10.1124/mol.61.2.320. PMID   11809856.
• Strausberg RL, Feingold EA, Grouse LH, et al. (2003). "Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences". Proc. Natl. Acad. Sci. U.S.A. 99 (26): 16899–903. Bibcode:2002PNAS...9916899M. doi: 10.1073/pnas.242603899 . PMC   139241 . PMID   12477932.
• Okubo T, Harada S, Higuchi S, Matsushita S (2004). "Association analyses between polymorphisms of the phase II detoxification enzymes (GSTM1, NQO1, NQO2) and alcohol withdrawal symptoms". Alcohol. Clin. Exp. Res. 27 (8 Suppl): 68S –71S. doi:10.1097/01.ALC.0000078616.63296.41. PMID   12960511.
• Ostrousky O, Meged S, Loewenthal R, et al. (2004). "NQO2 gene is associated with clozapine-induced agranulocytosis". Tissue Antigens. 62 (6): 483–91. doi:10.1046/j.1399-0039.2003.00133.x. PMID   14617031.
• Harada S, Tachikawa H, Kawanishi Y (2005). "A possible association between an insertion/deletion polymorphism of the NQO2 gene and schizophrenia". Psychiatr. Genet. 13 (4): 205–9. doi:10.1097/00041444-200312000-00003. PMID   14639047. S2CID   37313428.
• Ota T, Suzuki Y, Nishikawa T, et al. (2004). "Complete sequencing and characterization of 21,243 full-length human cDNAs". Nat. Genet. 36 (1): 40–5. doi: 10.1038/ng1285 . PMID   14702039. S2CID   21903526.
• Kwiek JJ, Haystead TA, Rudolph J (2004). "Kinetic mechanism of quinone oxidoreductase 2 and its inhibition by the antimalarial quinolines". Biochemistry. 43 (15): 4538–47. doi:10.1021/bi035923w. PMID   15078100.
• Buryanovskyy L, Fu Y, Boyd M, et al. (2004). "Crystal structure of quinone reductase 2 in complex with resveratrol". Biochemistry. 43 (36): 11417–26. doi:10.1021/bi049162o. PMC   3650734 . PMID   15350128.
• Wang W, Jaiswal AK (2005). "Sp3 repression of polymorphic human NRH:quinone oxidoreductase 2 gene promoter". Free Radic. Biol. Med. 37 (8): 1231–43. doi:10.1016/j.freeradbiomed.2004.06.042. PMID   15451063.
• Gerhard DS, Wagner L, Feingold EA, et al. (2004). "The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)". Genome Res. 14 (10B): 2121–7. doi:10.1101/gr.2596504. PMC   528928 . PMID   15489334.
• Hsieh TC, Wang Z, Hamby CV, Wu JM (2005). "Inhibition of melanoma cell proliferation by resveratrol is correlated with upregulation of quinone reductase 2 and p53". Biochem. Biophys. Res. Commun. 334 (1): 223–30. doi:10.1016/j.bbrc.2005.06.073. PMID   15993843.
• Fu Y, Buryanovskyy L, Zhang Z (2005). "Crystal structure of quinone reductase 2 in complex with cancer prodrug CB1954". Biochem. Biophys. Res. Commun. 336 (1): 332–8. doi:10.1016/j.bbrc.2005.08.081. PMID   16129418.
• Rual JF, Venkatesan K, Hao T, et al. (2005). "Towards a proteome-scale map of the human protein-protein interaction network". Nature. 437 (7062): 1173–8. Bibcode:2005Natur.437.1173R. doi:10.1038/nature04209. PMID   16189514. S2CID   4427026.

External links

• Overview of all the structural information available in the PDB for UniProt : P16083 (Ribosyldihydronicotinamide dehydrogenase [quinone]) at the PDBe-KB .