Human Gene FMO3 (ENST00000367755.9) from GENCODE V44
Description: Homo sapiens flavin containing dimethylaniline monoxygenase 3 (FMO3), transcript variant 1, mRNA. (from RefSeq NM_006894) RefSeq Summary (NM_001002294): Flavin-containing monooxygenases (FMO) are an important class of drug-metabolizing enzymes that catalyze the NADPH-dependent oxygenation of various nitrogen-,sulfur-, and phosphorous-containing xenobiotics such as therapeutic drugs, dietary compounds, pesticides, and other foreign compounds. The human FMO gene family is composed of 5 genes and multiple pseudogenes. FMO members have distinct developmental- and tissue-specific expression patterns. The expression of this FMO3 gene, the major FMO expressed in adult liver, can vary up to 20-fold between individuals. This inter-individual variation in FMO3 expression levels is likely to have significant effects on the rate at which xenobiotics are metabolised and, therefore, is of considerable interest to the pharmaceutical industry. This transmembrane protein localizes to the endoplasmic reticulum of many tissues. Alternative splicing of this gene results in multiple transcript variants encoding different isoforms. Mutations in this gene cause the disorder trimethylaminuria (TMAu) which is characterized by the accumulation and excretion of unmetabolized trimethylamine and a distinctive body odor. In healthy individuals, trimethylamine is primarily converted to the non odorous trimethylamine N-oxide.[provided by RefSeq, Jan 2016]. Gencode Transcript: ENST00000367755.9 Gencode Gene: ENSG00000007933.13 Transcript (Including UTRs) Position: hg38 chr1:171,090,905-171,117,819 Size: 26,915 Total Exon Count: 9 Strand: + Coding Region Position: hg38 chr1:171,092,659-171,117,442 Size: 24,784 Coding Exon Count: 8
ID:FMO3_HUMAN DESCRIPTION: RecName: Full=Dimethylaniline monooxygenase [N-oxide-forming] 3; EC=1.14.13.8; AltName: Full=Dimethylaniline oxidase 3; AltName: Full=FMO II; AltName: Full=FMO form 2; AltName: Full=Hepatic flavin-containing monooxygenase 3; Short=FMO 3; AltName: Full=Trimethylamine monooxygenase; EC=1.14.13.148; FUNCTION: Involved in the oxidative metabolism of a variety of xenobiotics such as drugs and pesticides. It N-oxygenates primary aliphatic alkylamines as well as secondary and tertiary amines. Plays an important role in the metabolism of trimethylamine (TMA), via the production of TMA N-oxide (TMAO). Is also able to perform S-oxidation when acting on sulfide compounds. CATALYTIC ACTIVITY: N,N-dimethylaniline + NADPH + O(2) = N,N- dimethylaniline N-oxide + NADP(+) + H(2)O. CATALYTIC ACTIVITY: N,N,N-trimethylamine + NADPH + O(2) = N,N,N- trimethylamine N-oxide + NADP(+) + H(2)O. COFACTOR: FAD. BIOPHYSICOCHEMICAL PROPERTIES: Kinetic parameters: KM=21 uM for trimethylamine (at pH 8.5); KM=31 uM for trimethylamine (at pH 7.4 and 37 degrees Celsius); KM=43 uM for benzydamine (at pH 7.4 and 37 degrees Celsius); KM=55.7 uM for ethylenethiourea (at pH 8.5); KM=71.8 uM for methimazole (at pH 8.5); KM=150.1 uM for sulindac (at pH 8.5); KM=248 uM for methyl p-tolyl sulfide (at pH 7.4 and 37 degrees Celsius); SUBCELLULAR LOCATION: Microsome membrane. Endoplasmic reticulum membrane. TISSUE SPECIFICITY: Liver. DISEASE: Defects in FMO3 are the cause of trimethylaminuria (TMAU) [MIM:602079]; also known as fish-odor syndrome. TMAU is an inborn error of metabolism associated with an offensive body odor and caused by deficiency of FMO-mediated N-oxidation of amino- trimethylamine (TMA) derived from foodstuffs. Such individuals excrete relatively large amounts of TMA in their urine, sweat, and breath, and exhibit a fishy body odor characteristic of the malodorous free amine. SIMILARITY: Belongs to the FMO family. WEB RESOURCE: Name=GeneReviews; URL="http://www.ncbi.nlm.nih.gov/sites/GeneTests/lab/gene/FMO3"; WEB RESOURCE: Name=NIEHS-SNPs; URL="http://egp.gs.washington.edu/data/fmo3/";
The RNAfold program from the Vienna RNA Package is used to perform the secondary structure predictions and folding calculations. The estimated folding energy is in kcal/mol. The more negative the energy, the more secondary structure the RNA is likely to have.
ModBase Predicted Comparative 3D Structure on P31513
Front
Top
Side
The pictures above may be empty if there is no ModBase structure for the protein. The ModBase structure frequently covers just a fragment of the protein. You may be asked to log onto ModBase the first time you click on the pictures. It is simplest after logging in to just click on the picture again to get to the specific info on that model.
Orthologous Genes in Other Species
Orthologies between human, mouse, and rat are computed by taking the best BLASTP hit, and filtering out non-syntenic hits. For more distant species reciprocal-best BLASTP hits are used. Note that the absence of an ortholog in the table below may reflect incomplete annotations in the other species rather than a true absence of the orthologous gene.