Family

Flavin monooxygenase (FMO) 3 (IPR002255)

Short name: Flavin_mOase_3

Family relationships

Description

Flavin-containing monooxygenases (FMOs) constitute a family of xenobiotic- metabolising enzymes [PMID: 8311461]. 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 diverse compounds. Five mammalian forms of FMO are now known and have been designated FMO1-FMO5 [PMID: 1712018, PMID: 2318837, PMID: 1542660, PMID: 1417778, PMID: 8486656].

The mRNA encoding FMO3 is abundant in adult liver and is also present, in low abundance, in some foetal tissues. Thus, like FMO1, FMO3 is subject to developmental and tissue-specific regulation, with a developmental switch in the expression of the genes taking place in the liver [PMID: 8654418]. The deduced amino acid sequence of human FM03 includes the putative FAD- (GxGxxG) and NADP+ pyrophosphate-binding (GxGxxA) sites characteristic of mammalian FMOs [PMID: 9344459], a 'FATGY' motif that has also been observed in a range of siderphore biosynthetic enzymes [PMID: 9538688], and a C-terminal hydrophobic segment that is believed to anchor the monooxygenase to the microsomal membrane [PMID: 2355001]. Mutations in human FMO3 impair N-oxygenation of xenobiotics and are responsible for the trimethylaminuria phenotype [PMID: 9536088]. Three disease-causing mutations have been identified. Nonsense and missense mutations are associated with a severe phenotype and are also implicated in impaired metabolism of other nitrogen- and sulphur-containing substrates, including biogenic amines, both clinically and when mutated proteins expressed from cDNA are studied in vitro [PMID: 9536088]. Human FMO3 thus plays a critical role in the metabolism of xenobiotic substrates and endogenous amines.

GO terms

Biological Process

GO:0055114 oxidation-reduction process

Molecular Function

GO:0004499 N,N-dimethylaniline monooxygenase activity

Cellular Component

No terms assigned in this category.

Contributing signatures

Signatures from InterPro member databases are used to construct an entry.
PRINTS