Carbonyl reductase [NADPH] 1 (CBR1)
The protein contains 277 amino acids for an estimated molecular weight of 30375 Da.
NADPH-dependent reductase with broad substrate specificity. Catalyzes the reduction of a wide variety of carbonyl compounds including quinones, prostaglandins, menadione, plus various xenobiotics. Catalyzes the reduction of the antitumor anthracyclines doxorubicin and daunorubicin to the cardiotoxic compounds doxorubicinol and daunorubicinol (PubMed:18449627, PubMed:15799708, PubMed:17912391, PubMed:7005231). Can convert prostaglandin E to prostaglandin F2-alpha (By similarity). Can bind glutathione, which explains its higher affinity for glutathione-conjugated substrates. Catalyzes the reduction of S-nitrosoglutathione (PubMed:18826943, PubMed:17344335). (updated: Aug. 12, 2020)
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.
- D'Alessandro and co-workers. (2017) Red blood cell proteomics update: is there more to discover? Blood Transfus. 15(2), 182-187.
- Bryk and co-workers. (2017) Quantitative Analysis of Human Red Blood Cell Proteome. J Proteome Res. 16(8), 2752-2761.
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.
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Biological Process
Arachidonic acid metabolic process
Cyclooxygenase pathway
Drug metabolic process
Epithelial cell differentiation
Oxidation-reduction process
Positive regulation of reactive oxygen species metabolic process
Small molecule metabolic process
Vitamin K metabolic process
Molecular Function
15-hydroxyprostaglandin dehydrogenase (NAD+) activity
15-hydroxyprostaglandin dehydrogenase (NADP+) activity
15-hydroxyprostaglandin-D dehydrogenase (NADP+) activity
Androstan-3-alpha,17-beta-diol dehydrogenase activity
Carbonyl reductase (NADPH) activity
Oxidoreductase activity, acting on NAD(P)H, quinone or similar compound as acceptor
Prostaglandin-E2 9-reductase activity
The reference OMIM entry for this protein is 114830
Carbonyl reductase 1; cbr1
Carbonyl reductase; cbr
DESCRIPTION
Carbonyl reductase (EC 1.1.1.184) is 1 of several monomeric, NADPH-dependent oxidoreductases having wide specificity for carbonyl compounds that are generally referred to as aldo-keto reductases. Others include aldehyde reductase (EC 1.1.1.2; 103830) and aldose reductase (EC 1.1.1.21; 103880).CLONING
Wermuth et al. (1988) isolated and characterized a cDNA complementary to carbonyl reductase mRNA from a human placenta cDNA library. The cDNA contained an open reading frame encoding a protein comprised of 277 amino acids with a molecular weight of 30,375. Comparison of the predicted protein sequence with the primary structures of other aldo-keto reductases showed no significant homologies. A possible homology, on the other hand, was found between carbonyl reductase and 'short' subunit alcohol/polyol dehydrogenases. The enzyme is widely distributed in human tissues and also occurs in other mammalian and nonmammalian species. In a carbonyl reductase cDNA cloned from a breast cancer cell line, Forrest et al. (1990) demonstrated 1,219 basepairs. Southern analysis of genomic DNA digested with several restriction enzymes and analyzed by hybridization with a labeled cDNA probe indicated that carbonyl reductase is probably coded by a single gene and does not belong to a family of structurally similar enzymes. Carbonyl reductase mRNA was induced 3- or 4-fold in 24 hours with BHA, beta-naphthoflavone, or Sudan 1.MAPPING
By Southern blot analysis of 17 mouse/human somatic cell hybrids, Forrest et al. (1990) showed that the CBR gene is located on chromosome 21. Avramopoulos et al. (1992) confirmed assignment to chromosome 21 by genetic linkage mapping using a DNA polymorphism from the 3-prime untranslated region of the CBR gene. They demonstrated, furthermore, that the gene lies between the interferon-alpha receptor gene (107450) and D21S55, being about 3.4 and 7.2 cM, respectively, from the 2 flanking loci. The findings placed CBR in the telomeric band 21q22.3. By high-resolution fluorescence in situ hybridization, Lemieux et al. (1993) mapped the CBR gene to 21q22.12, very close to the SOD1 locus at position 21q22.11. CBR displayed gene dosage effects in trisomy 21 human lymphoblasts at both the DNA and the mRNA levels. With increasing chromosome 21 ploidy, lymphoblasts also showed increased aldo-keto reductase activity and increased quinone reductase activity. Both of these activities have been shown to be associated with carbonyl reductase. The location of CBR near SOD1 and the increased enzyme activity and potential for free radical modulation in trisomy 21 cells implicate CBR as a candidate for contributing to the pathology of Down syndrome. Wei et al. (1996) mapped the mouse Cbr1 gene to distal chromosome 16, as had others. They identified a second carbonyl reductase gene in mouse (Cbr2) and found that it mapped to distal chromosome 11.GENE STRUCTURE
By sequence analysis of human chromosome region 21q22.2, Watanabe et al. (1998) determined that the CBR1 gene contains 3 exons and spans 3.3 kb. They identified a related gene, CBR3 (603608), 62 kb telomeric to CBR1.GENE FUNCTION
Carbonyl reductase catalyzes the reduction of a great variety of carbonyl compounds, e.g., quinones derived from polycyclic aromatic hydrocarbons, 9-ketoprostaglandins, and the antitumor anthracycline antibiotics daunorubicin and doxorubicin (Wermuth et al., 1988). ... More on the omim web site
Aug. 24, 2020: Protein entry updated
Automatic update: Entry updated from uniprot information.
June 29, 2020: Protein entry updated
Automatic update: Entry updated from uniprot information.
Feb. 2, 2018: Protein entry updated
Automatic update: Uniprot description updated
Dec. 19, 2017: Protein entry updated
Automatic update: Uniprot description updated
Nov. 23, 2017: Protein entry updated
Automatic update: Uniprot description updated
March 16, 2016: Protein entry updated
Automatic update: OMIM entry 114830 was added.
Jan. 27, 2016: Protein entry updated
Automatic update: model status changed
Jan. 24, 2016: Protein entry updated
Automatic update: model status changed