Ribosyldihydronicotinamide dehydrogenase [quinone] (NQO2)
The protein contains 231 amino acids for an estimated molecular weight of 25919 Da.
The enzyme apparently serves as a quinone reductase in connection with conjugation reactions of hydroquinones involved in detoxification pathways as well as in biosynthetic processes such as the vitamin K-dependent gamma-carboxylation of glutamate residues in prothrombin synthesis. (updated: April 1, 2015)
Protein identification was indicated in the following studies:
- Goodman and co-workers. (2013) The proteomics and interactomics of human erythrocytes. Exp Biol Med (Maywood) 238(5), 509-518.
- Lange and co-workers. (2014) Annotating N termini for the human proteome project: N termini and Nα-acetylation status differentiate stable cleaved protein species from degradation remnants in the human erythrocyte proteome. J Proteome Res. 13(4), 2028-2044.
- Hegedűs and co-workers. (2015) Inconsistencies in the red blood cell membrane proteome analysis: generation of a database for research and diagnostic applications. Database (Oxford) 1-8.
- Bryk and co-workers. (2017) Quantitative Analysis of Human Red Blood Cell Proteome. J Proteome Res. 16(8), 2752-2761.
- D'Alessandro and co-workers. (2017) Red blood cell proteomics update: is there more to discover? Blood Transfus. 15(2), 182-187.
Methods
The following articles were analysed to gather the proteome content of erythrocytes.
The gene or protein list provided in the studies were processed using the ID mapping API of Uniprot in September 2018. The number of proteins identified and mapped without ambiguity in these studies is indicated below.
Only Swiss-Prot entries (reviewed) were considered for protein evidence assignation.
| Publication | Identification 1 | Uniprot mapping 2 | Not mapped / Obsolete | TrEMBL | Swiss-Prot |
|---|---|---|---|---|---|
| Goodman (2013) | 2289 (gene list) | 2278 | 53 | 20599 | 2269 |
| Lange (2014) | 1234 | 1234 | 7 | 28 | 1224 |
| Hegedus (2015) | 2638 | 2622 | 0 | 235 | 2387 |
| Wilson (2016) | 1658 | 1528 | 170 | 291 | 1068 |
| d'Alessandro (2017) | 1826 | 1817 | 2 | 0 | 1815 |
| Bryk (2017) | 2090 | 2060 | 10 | 108 | 1942 |
| Chu (2018) | 1853 | 1804 | 55 | 362 | 1387 |
1 as available in the article and/or in supplementary material
2 uniprot mapping returns all protein isoforms as one entry
The compilation of older studies can be retrieved from the Red Blood Cell Collection database.
The data and differentiation stages presented below come from the proteomic study and analysis performed by our partners of the GReX consortium, more details are available in their published work.
(right-click above to access to more options from the contextual menu)
| Variant | Description |
|---|---|
| dbSNP:rs28383623 | |
| dbSNP:rs17136117 | |
| dbSNP:rs1143684 | |
| dbSNP:rs17300141 | |
| dbSNP:rs28383651 |
Biological Process
Memory
Oxidation-reduction process
Positive regulation of ERK1 and ERK2 cascade
Positive regulation of neuron apoptotic process
Positive regulation of reactive oxygen species metabolic process
Positive regulation of vascular associated smooth muscle cell proliferation
Quinone catabolic process
Xenobiotic metabolic process
Molecular Function
Chloride ion binding
Dihydronicotinamide riboside quinone reductase activity
Electron transfer activity
FAD binding
Melatonin binding
Metal ion binding
NAD(P)H dehydrogenase (quinone) activity
NADPH dehydrogenase (quinone) activity
Oxidoreductase activity
Oxidoreductase activity, acting on other nitrogenous compounds as donors
Protein homodimerization activity
Resveratrol binding
Zinc ion binding
The reference OMIM entry for this protein is 160998
Nad(p)h dehydrogenase, quinone 2; nqo2
Nad(p)h:menadione oxidoreductase 1, dioxin-inducible 2; nmor2
DESCRIPTION
NQO2 (EC 1.10.99.2) is a flavoprotein that catalyzes the 2-electron reduction of various quinones, redox dyes, and the vitamin K menadione. NQO2 predominantly uses dihydronicotinamide riboside (NRH) as the electron donor (summary by Wu et al., 1997).CLONING
Jaiswal et al. (1988) described a cDNA that encodes a dioxin-inducible cytosolic form of human NAD(P)H:quinone oxidoreductase (NQO1; 125860). Jaiswal et al. (1990) cloned a cDNA clone that encodes a second form of this oxidoreductase, NQO2. It was isolated by screening a human liver cDNA library by hybridization with an NQO1 cDNA probe. The deduced 231-amino acid NQO2 protein has a calculated molecular mass of 25.95 kD and shares 49% similarity with the liver cytosolic NQO1 protein. Using Northern blot analysis, Jaiswal (1994) detected variable expression of a single 1.2-kb NQO2 transcript in several human tissues, with highest expression in skeletal muscle, and little to no expression in pancreas and placenta. Gaikwad et al. (2009) stated that NQO2 is ubiquitously expressed.GENE FUNCTION
By in vitro assay of human NQO2 expressed in transfected COS-1 cells, Jaiswal (1994) showed that NQO2 catalyzed nitroreduction of an antitumor analog of nitrophenylaziridine. However, unlike NQO1, NQO2 could not efficiently reduce DCIP (2,6-dichlorophenolindophenol) and menadione. Wu et al. (1997) found that NQO2, like NQO1, functioned as a dimer with 1 FAD prosthetic group per 26-kD subunit. NRH was an efficient electron donor for NQO2-mediated 2-electron reduction of menadione and DCIP; however, NADH was a poor electron donor. NQO2 did not reduce 1-electron acceptors, such as potassium ferricyanide. NQO2 also catalyzed a 4-electron reduction of methyl red and a cytotoxic compound, CB 1954 (5-(aziridine-1-yl)-2,4-dinitrobenzamide). NQO2 was resistant to typical inhibitors of NQO1 and was sensitive to a different group of flavone inhibitors, including quercetin, a competitive inhibitor of NRH. Estrogens are metabolized to reactive catechol estrogen quinones, and these quinones can depurinate DNA, leading to cancer-causing mutations. Using mass spectrometry, Gaikwad et al. (2009) showed that NQO2 could bind estrone-3,4-quinone (E1-3,4-Q) and estradiol-3,4-quinone (E2-3,4-Q). Preliminary kinetic studies revealed that NQO2 was faster in reducing and deactivating the estrogen quinones than NQO1. The reduction of E1-3,4-Q and E2-3,4-Q by NQO2 was confirmed by ultraviolet and liquid chromatography-tandem mass spectrometry assays. Both estrogens and melatonin bound NQO2, but melatonin did not affect estrogen quinone reduction by NQO2.GENE STRUCTURE
By Southern blot analysis, Jaiswal et al. (1990) demonstrated the presence of a single human NQO2 gene spanning approximately 14 to 17 kb. Jaiswal (1994) determined that the NQO2 gene contains 7 exons and spans 20 kb. The first exon is noncoding. The promoter region contains a modified TATA box, 2 CCAAT boxes, 4 SP1 (189906)-binding sites, a single antioxidant response element (ARE), and 3 xenobiotic response elements (XREs).MAPPING
By study of rodent/human somatic cell hybrids, Jaiswal et al. (1990) mapped the NQO2 gene to chromosome 6pter-q12. By fluorescence in situ hybridization, Jaiswal et al. (1999) narrowed the mapping of NQO2 to chromosome 6p25.MOLECULAR GENETICS
In a hospital-based study of 893 Chinese breast cancer patients and 711 Chinese cancer-free controls, Yu et al. ... More on the omim web site
Feb. 2, 2018: Protein entry updated
Automatic update: Uniprot description updated
Dec. 19, 2017: Protein entry updated
Automatic update: Uniprot description updated
March 16, 2016: Protein entry updated
Automatic update: OMIM entry 160998 was added.
Jan. 28, 2016: Protein entry updated
Automatic update: model status changed
Jan. 25, 2016: Protein entry updated
Automatic update: model status changed