| Primary Identifier | IPR002255 | Type | Family |
| Short Name | Flavin_mOase_3 |
| description | Flavin-containing monooxygenases (FMOs) constitute a family of xenobiotic-metabolising enzymes []. Using an NADPH cofactor and FAD prosthetic group,these microsomal proteins catalyse the oxygenation of nucleophilic nitrogen,sulphur, phosphorous and selenium atoms in a range of structurally diversecompounds. Five mammalian forms of FMO are now known and have been designatedFMO1-FMO5 [, , , , ].The mRNA encoding FMO3 is abundant in adult liver and is also present, inlow abundance, in some foetal tissues. Thus, like FMO1, FMO3 is subjectto developmental and tissue-specific regulation, with a developmental switchin the expression of the genes taking place in the liver []. The deduced amino acid sequence of human FM03 includes the putative FAD-(GxGxxG) and NADP+pyrophosphate-binding (GxGxxA) sites characteristic ofmammalian FMOs [], a 'FATGY' motif that has also been observed in a rangeof siderphore biosynthetic enzymes [], and a C-terminal hydrophobic segment that is believed to anchor the monooxygenase to the microsomal membrane [].Mutations in human FMO3 impair N-oxygenation of xenobiotics and are responsible for the trimethylaminuria phenotype []. Three disease-causingmutations have been identified. Nonsense and missense mutations are associated with a severe phenotype and are also implicated in impairedmetabolism of other nitrogen- and sulphur-containing substrates, includingbiogenic amines, both clinically and when mutated proteins expressed fromcDNA are studied in vitro []. Human FMO3 thus plays a critical role in themetabolism of xenobiotic substrates and endogenous amines. |
