CYB5R3
NADH-cytochrome b5 reductase 3 is an enzyme that in humans is encoded by the CYB5R3 gene.[1][2]
Two forms of NADH-cytochrome b5 reductase are known, a membrane-bound form in somatic cells (anchored in the endoplasmic reticulum, mitochondrial and other membranes) and a soluble form in erythrocytes. The former exists mainly on the cytoplasmic side of the endoplasmic reticulum and functions in desaturation and elongation of fatty acids, in cholesterol biosynthesis, and in drug metabolism. The erythrocyte form is located in a soluble fraction of circulating erythrocytes and is involved in methemoglobin reduction. The membrane-bound form has both membrane-binding and catalytic domains. The soluble form has only the catalytic domain. This gene encodes both forms of the enzyme which arise from tissue-specific alternative transcripts that differ in the first exon. Mutations in this gene cause methemoglobinemias.[3]
References
Further reading
- Narahara K, Takahashi Y, Murakami M, et al. (1992). "Terminal 22q deletion associated with a partial deficiency of arylsulphatase A.". J. Med. Genet. 29 (6): 432–3. doi:10.1136/jmg.29.6.432. PMC 1016000. PMID 1352356. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=1016000.
- Dailey HA, Strittmatter P (1979). "Modification and identification of cytochrome b5 carboxyl groups involved in protein-protein interaction with cytochrome b5 reductase.". J. Biol. Chem. 254 (12): 5388–96. PMID 221468.
- Malkinson AM, Siegel D, Forrest GL, et al. (1992). "Elevated DT-diaphorase activity and messenger RNA content in human non-small cell lung carcinoma: relationship to the response of lung tumor xenografts to mitomycin Cł.". Cancer Res. 52 (17): 4752–7. PMID 1324793.
- Shirabe K, Yubisui T, Borgese N, et al. (1992). "Enzymatic instability of NADH-cytochrome b5 reductase as a cause of hereditary methemoglobinemia type I (red cell type).". J. Biol. Chem. 267 (28): 20416–21. PMID 1400360.
- Katsube T, Sakamoto N, Kobayashi Y, et al. (1991). "Exonic point mutations in NADH-cytochrome B5 reductase genes of homozygotes for hereditary methemoglobinemia, types I and III: putative mechanisms of tissue-dependent enzyme deficiency.". Am. J. Hum. Genet. 48 (4): 799–808. PMC 1682939. PMID 1707593. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=1682939.
- Yubisui T, Shirabe K, Takeshita M, et al. (1991). "Structural role of serine 127 in the NADH-binding site of human NADH-cytochrome b5 reductase.". J. Biol. Chem. 266 (1): 66–70. PMID 1898726.
- Shirabe K, Yubisui T, Nishino T, Takeshita M (1991). "Role of cysteine residues in human NADH-cytochrome b5 reductase studied by site-directed mutagenesis. Cys-273 and Cys-283 are located close to the NADH-binding site but are not catalytically essential.". J. Biol. Chem. 266 (12): 7531–6. PMID 2019583.
- Kobayashi Y, Fukumaki Y, Yubisui T, et al. (1990). "Serine-proline replacement at residue 127 of NADH-cytochrome b5 reductase causes hereditary methemoglobinemia, generalized type.". Blood 75 (7): 1408–13. PMID 2107882.
- Strittmatter P, Hackett CS, Korza G, Ozols J (1991). "Characterization of the covalent cross-links of the active sites of amidinated cytochrome b5 and NADH:cytochrome b5 reductase.". J. Biol. Chem. 265 (35): 21709–13. PMID 2123873.
- Murakami K, Yubisui T, Takeshita M, Miyata T (1989). "The NH2-terminal structures of human and rat liver microsomal NADH-cytochrome b5 reductases.". J. Biochem. 105 (2): 312–7. PMID 2498303.
- Yubisui T, Naitoh Y, Zenno S, et al. (1987). "Molecular cloning of cDNAs of human liver and placenta NADH-cytochrome b5 reductase.". Proc. Natl. Acad. Sci. U.S.A. 84 (11): 3609–13. doi:10.1073/pnas.84.11.3609. PMC 304924. PMID 3035541. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=304924.
- Yubisui T, Miyata T, Iwanaga S, et al. (1986). "Complete amino acid sequence of NADH-cytochrome b5 reductase purified from human erythrocytes.". J. Biochem. 99 (2): 407–22. PMID 3700359.
- Passon PG, Hultquist DE (1972). "Soluble cytochrome b 5 reductase from human erythrocytes.". Biochim. Biophys. Acta 275 (1): 62–73. doi:10.1016/0005-2728(72)90024-2. PMID 4403130.
- Yubisui T, Miyata T, Iwanaga S, et al. (1985). "Amino acid sequence of NADH-cytochrome b5 reductase of human erythrocytes.". J. Biochem. 96 (2): 579–82. PMID 6389526.
- Shirabe K, Landi MT, Takeshita M, et al. (1995). "A novel point mutation in a 3' splice site of the NADH-cytochrome b5 reductase gene results in immunologically undetectable enzyme and impaired NADH-dependent ascorbate regeneration in cultured fibroblasts of a patient with type II hereditary methemoglobinemia.". Am. J. Hum. Genet. 57 (2): 302–10. PMC 1801527. PMID 7668255. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=1801527.
- Vieira LM, Kaplan JC, Kahn A, Leroux A (1995). "Four new mutations in the NADH-cytochrome b5 reductase gene from patients with recessive congenital methemoglobinemia type II.". Blood 85 (8): 2254–62. PMID 7718898.
- Shirabe K, Fujimoto Y, Yubisui T, Takeshita M (1994). "An in-frame deletion of codon 298 of the NADH-cytochrome b5 reductase gene results in hereditary methemoglobinemia type II (generalized type). A functional implication for the role of the COOH-terminal region of the enzyme.". J. Biol. Chem. 269 (8): 5952–7. PMID 8119939.
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PDB gallery
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1ndh: CRYSTAL STRUCTURE OF NADH-CYTOCHROME B5 REDUCTASE FROM PIG LIVER AT 2.4 ANGSTROMS RESOLUTION
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1umk: The Structure of Human Erythrocyte NADH-cytochrome b5 Reductase
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