Flavin-containing monooxygenase 2 (FMO2), also known as dimethylaniline monooxygenase [N-oxide-forming] 2, is a mammalian enzyme that in humans is encoded by the FMO2 gene.[5][6][7] The gene is found in a cluster with the FMO1, FMO3, and FMO4 genes on chromosome 1.[7]
FMO2 is a member of the family of flavin-containing monooxygenases, NADPH-dependent enzymes that catalyze the oxidation of many drugs and xenobiotics. It catalyzes the N-oxidation of some primary alkylamines through an N-hydroxylamine intermediate.[7]
In humans, FMO2 is expressed in lung tissue.[8] The most common isoform, FMO2*2A, contains a premature stop codon, leading to a truncated protein with no catalytic activity that is probably rapidly degraded.[7] The other isoform, FMO2*1, present in sub-Saharan Africans (up to 50%), African-Americans (26%) and Hispanics (2–7%), is functional.[8][9] Its substrates include thioether-containing pesticides, the anti-tuberculosis drug ethionamide, as well as α-naphthylthiourea and other thioureas.[9]
References
- ^ a b c GRCh38: Ensembl release 89: ENSG00000094963 – Ensembl, May 2017
- ^ a b c GRCm38: Ensembl release 89: ENSMUSG00000040170 – Ensembl, May 2017
- ^ "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
- ^ "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
- ^ Dolphin CT, Shephard EA, Povey S, Smith RL, Phillips IR (Nov 1992). "Cloning, primary sequence and chromosomal localization of human FMO2, a new member of the flavin-containing mono-oxygenase family". Biochem J. 287. ( Pt 1) (Pt 1): 261–7. doi:10.1042/bj2870261. PMC 1133153. PMID 1417778.
- ^ Dolphin CT, Beckett DJ, Janmohamed A, Cullingford TE, Smith RL, Shephard EA, Phillips IR (Dec 1998). "The flavin-containing monooxygenase 2 gene (FMO2) of humans, but not of other primates, encodes a truncated, nonfunctional protein". J Biol Chem. 273 (46): 30599–607. doi:10.1074/jbc.273.46.30599. PMID 9804831.
- ^ a b c d "Entrez Gene: FMO2 flavin containing monooxygenase 2 (non-functional)".
- ^ a b Online Mendelian Inheritance in Man (OMIM): 603955
- ^ a b Veeramah KR, Thomas MG, Weale ME, Zeitlyn D, Tarekegn A, Bekele E, Mendell NR, Shephard EA, Bradman N, Phillips IR (October 2008). "The potentially deleterious functional variant flavin-containing monooxygenase 2*1 is at high frequency throughout sub-Saharan Africa". Pharmacogenetics and Genomics. 18 (10): 877–886. doi:10.1097/fpc.0b013e3283097311.
Further reading
- Hines RN, Cashman JR, Philpot RM, et al. (1994). "The mammalian flavin-containing monooxygenases: molecular characterization and regulation of expression". Toxicol. Appl. Pharmacol. 125 (1): 1–6. doi:10.1006/taap.1994.1042. PMID 8128486.
- Lomri N, Gu Q, Cashman JR (1992). "Molecular cloning of the flavin-containing monooxygenase (form II) cDNA from adult human liver". Proc. Natl. Acad. Sci. U.S.A. 89 (5): 1685–9. Bibcode:1992PNAS...89.1685L. doi:10.1073/pnas.89.5.1685. PMC 48517. PMID 1542660.
- Phillips IR, Dolphin CT, Clair P, et al. (1995). "The molecular biology of the flavin-containing monooxygenases of man". Chem. Biol. Interact. 96 (1): 17–32. Bibcode:1995CBI....96...17P. doi:10.1016/0009-2797(94)03580-2. PMID 7720101.
- Lawton MP, Cashman JR, Cresteil T, et al. (1994). "A nomenclature for the mammalian flavin-containing monooxygenase gene family based on amino acid sequence identities". Arch. Biochem. Biophys. 308 (1): 254–7. doi:10.1006/abbi.1994.1035. PMID 8311461.
- McCombie RR, Dolphin CT, Povey S, et al. (1996). "Localization of human flavin-containing monooxygenase genes FMO2 and FMO5 to chromosome 1q". Genomics. 34 (3): 426–9. doi:10.1006/geno.1996.0308. PMID 8786146.
- Bonaldo MF, Lennon G, Soares MB (1997). "Normalization and subtraction: two approaches to facilitate gene discovery". Genome Res. 6 (9): 791–806. doi:10.1101/gr.6.9.791. PMID 8889548.
- Whetstine JR, Yueh MF, McCarver DG, et al. (2000). "Ethnic differences in human flavin-containing monooxygenase 2 (FMO2) polymorphisms: detection of expressed protein in African-Americans". Toxicol. Appl. Pharmacol. 168 (3): 216–24. doi:10.1006/taap.2000.9050. PMID 11042094.
- Krueger SK, Martin SR, Yueh MF, et al. (2002). "Identification of active flavin-containing monooxygenase isoform 2 in human lung and characterization of expressed protein". Drug Metab. Dispos. 30 (1): 34–41. doi:10.1124/dmd.30.1.34. PMID 11744609. S2CID 9151632.
- 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.
- Furnes B, Feng J, Sommer SS, Schlenk D (2003). "Identification of novel variants of the flavin-containing monooxygenase gene family in African Americans". Drug Metab. Dispos. 31 (2): 187–93. doi:10.1124/dmd.31.2.187. PMID 12527699. S2CID 6619389.
- 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.
- 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.
- Krueger SK, Siddens LK, Henderson MC, et al. (2005). "Haplotype and functional analysis of four flavin-containing monooxygenase isoform 2 (FMO2) polymorphisms in Hispanics". Pharmacogenet. Genomics. 15 (4): 245–56. doi:10.1097/01213011-200504000-00008. PMC 1351039. PMID 15864117.
- Gregory SG, Barlow KF, McLay KE, et al. (2006). "The DNA sequence and biological annotation of human chromosome 1". Nature. 441 (7091): 315–21. Bibcode:2006Natur.441..315G. doi:10.1038/nature04727. PMID 16710414.