Alternative titles; symbols
HGNC Approved Gene Symbol: CBR1
Cytogenetic location: 21q22.12 Genomic coordinates (GRCh38): 21:36,070,024-36,073,164 (from NCBI)
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).
Wermuth et al. (1988) isolated and characterized a cDNA complementary to carbonyl reductase mRNA from a human placenta cDNA library. The deduced 277-amino acid protein has a molecular mass of 30,375 Da. 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.
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.
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.
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).
Avramopoulos, D., Cox, T., Forrest, G. L., Chakravarti, A., Antonarakis, S. E. Linkage mapping of the carbonyl reductase (CBR) gene on human chromosome 21 using a DNA polymorphism in the 3-prime untranslated region. Genomics 13: 447-448, 1992. [PubMed: 1612603] [Full Text: https://doi.org/10.1016/0888-7543(92)90268-w]
Forrest, G. L., Akman, S., Krutzik, S., Paxton, R. J., Sparkes, R. S., Doroshow, J., Felsted, R. L., Glover, C. J., Mohandas, T., Bachur, N. R. Induction of a human carbonyl reductase gene located on chromosome 21. Biochim. Biophys. Acta 1048: 149-155, 1990. [PubMed: 2182121] [Full Text: https://doi.org/10.1016/0167-4781(90)90050-c]
Lemieux, N., Malfoy, B., Forrest, G. L. Human carbonyl reductase (CBR) localized to band 21q22.1 by high-resolution fluorescence in situ hybridization displays gene dosage effects in trisomy 21 cells. Genomics 15: 169-172, 1993. [PubMed: 8432528] [Full Text: https://doi.org/10.1006/geno.1993.1024]
Watanabe, K., Sugawara, C., Ono, A., Fukuzumi, Y., Itakura, S., Yamazaki, M., Tashiro, H., Osoegawa, K., Soeda, E., Nomura, T. Mapping of a novel human carbonyl reductase, CBR3, and ribosomal pseudogenes to human chromosome 21q22.2. Genomics 52: 95-100, 1998. [PubMed: 9740676] [Full Text: https://doi.org/10.1006/geno.1998.5380]
Wei, J., Dlouhy, S. R., Hara, A., Ghetti, B., Hodes, M. E. Cloning a cDNA for carbonyl reductase (Cbr) from mouse cerebellum: murine genes that express Cbr map to chromosomes 16 and 11. Genomics 34: 147-148, 1996. [PubMed: 8661038] [Full Text: https://doi.org/10.1006/geno.1996.0255]
Wermuth, B., Bohren, K. M., Heinemann, G., von Wartburg, J.-P., Gabbay, K. H. Human carbonyl reductase: nucleotide sequence analysis of a cDNA and amino acid sequence of the encoded protein. J. Biol. Chem. 263: 16185-16188, 1988. [PubMed: 3141401]