Flavin-containing monooxygenase 3

Details

Name
Flavin-containing monooxygenase 3
Synonyms
  • 1.14.13.148
  • 1.14.13.32
  • 1.14.13.8
  • Dimethylaniline monooxygenase [N-oxide-forming] 3
  • Dimethylaniline oxidase 3
  • FMO 3
  • FMO form 2
  • FMO II
  • Hepatic flavin-containing monooxygenase 3
  • Trimethylamine monooxygenase
Gene Name
FMO3
UniProtKB Entry
P31513Swiss-Prot
Organism
Humans
NCBI Taxonomy ID
9606
Amino acid sequence
>lcl|BSEQ0012507|Flavin-containing monooxygenase 3
MGKKVAIIGAGVSGLASIRSCLEEGLEPTCFEKSNDIGGLWKFSDHAEEGRASIYKSVFS
NSSKEMMCFPDFPFPDDFPNFMHNSKIQEYIIAFAKEKNLLKYIQFKTFVSSVNKHPDFA
TTGQWDVTTERDGKKESAVFDAVMVCSGHHVYPNLPKESFPGLNHFKGKCFHSRDYKEPG
VFNGKRVLVVGLGNSGCDIATELSRTAEQVMISSRSGSWVMSRVWDNGYPWDMLLVTRFG
TFLKNNLPTAISDWLYVKQMNARFKHENYGLMPLNGVLRKEPVFNDELPASILCGIVSVK
PNVKEFTETSAIFEDGTIFEGIDCVIFATGYSFAYPFLDESIIKSRNNEIILFKGVFPPL
LEKSTIAVIGFVQSLGAAIPTVDLQSRWAAQVIKGTCTLPSMEDMMNDINEKMEKKRKWF
GKSETIQTDYIVYMDELSSFIGAKPNIPWLFLTDPKLAMEVYFGPCSPYQFRLVGPGQWP
GARNAILTQWDRSLKPMQTRVVGRLQKPCFFFHWLKLFAIPILLIAVFLVLT
Number of residues
532
Molecular Weight
60032.975
Theoretical pI
7.87
GO Classification
Functions
albendazole monooxygenase activity / hypotaurine dehydrogenase activity
Processes
taurine biosynthetic process
General Function
Essential hepatic enzyme that catalyzes the oxygenation of a wide variety of nitrogen- and sulfur-containing compounds including drugs as well as dietary compounds (PubMed:10759686, PubMed:30381441, PubMed:32156684). Plays an important role in the metabolism of trimethylamine (TMA), via the production of trimethylamine N-oxide (TMAO) metabolite (PubMed:9776311). TMA is generated by the action of gut microbiota using dietary precursors such as choline, choline containing compounds, betaine or L-carnitine. By regulating TMAO concentration, FMO3 directly impacts both platelet responsiveness and rate of thrombus formation (PubMed:29981269)
Specific Function
Albendazole monooxygenase activity
Pfam Domain Function
Signal Regions
Not Available
Transmembrane Regions
510-530
Cellular Location
Microsome membrane
Gene sequence
>lcl|BSEQ0012508|Dimethylaniline monooxygenase [N-oxide-forming] 3 (FMO3)
ATGGGGAAGAAAGTGGCCATCATTGGAGCTGGTGTGAGTGGCTTGGCCTCCATCAGGAGC
TGTCTGGAAGAGGGGCTGGAGCCCACCTGCTTTGAGAAGAGCAATGACATTGGGGGCCTG
TGGAAATTTTCAGACCATGCAGAGGAGGGCAGGGCTAGCATTTACAAATCAGTCTTTTCC
AACTCTTCCAAAGAGATGATGTGTTTCCCAGACTTCCCATTTCCCGATGACTTCCCCAAC
TTTATGCACAACAGCAAGATCCAGGAATATATCATTGCATTTGCCAAAGAAAAGAACCTC
CTGAAGTACATACAATTTAAGACATTTGTATCCAGTGTAAATAAACATCCTGATTTTGCA
ACTACTGGCCAGTGGGATGTTACCACTGAAAGGGATGGTAAAAAAGAATCGGCTGTCTTT
GATGCTGTAATGGTTTGTTCCGGACATCATGTGTATCCCAACCTACCAAAAGAGTCCTTT
CCAGGACTAAACCACTTTAAAGGCAAATGCTTCCACAGCAGGGACTATAAAGAACCAGGT
GTATTCAATGGAAAGCGTGTCCTGGTGGTTGGCCTGGGGAATTCGGGCTGTGATATTGCC
ACAGAACTCAGCCGCACAGCAGAACAGGTCATGATCAGTTCCAGAAGTGGCTCCTGGGTG
ATGAGCCGGGTCTGGGACAATGGTTATCCTTGGGACATGCTGCTCGTCACTCGATTTGGA
ACCTTCCTCAAGAACAATTTACCGACAGCCATCTCTGACTGGTTGTACGTGAAGCAGATG
AATGCAAGATTCAAGCATGAAAACTATGGCTTGATGCCTTTAAATGGAGTCCTGAGGAAA
GAGCCTGTATTTAACGATGAGCTCCCAGCAAGCATTCTGTGTGGCATTGTGTCCGTAAAG
CCTAACGTGAAGGAATTCACAGAGACCTCGGCCATTTTTGAGGATGGGACCATATTTGAG
GGCATTGACTGTGTAATCTTTGCAACAGGGTATAGTTTTGCCTACCCCTTCCTTGATGAG
TCTATCATCAAAAGCAGAAACAATGAGATCATTTTATTTAAAGGAGTATTTCCTCCTCTA
CTTGAGAAGTCAACCATAGCAGTGATTGGCTTTGTCCAGTCCCTTGGGGCTGCCATTCCC
ACAGTTGACCTCCAGTCCCGCTGGGCAGCACAAGTAATAAAGGGAACTTGTACTTTGCCT
TCTATGGAAGACATGATGAATGATATTAATGAGAAAATGGAGAAAAAGCGCAAATGGTTT
GGCAAAAGCGAGACCATACAGACAGATTACATTGTTTATATGGATGAACTCTCCTCCTTC
ATTGGGGCAAAGCCCAACATCCCATGGCTGTTTCTCACAGATCCCAAATTGGCCATGGAA
GTTTATTTTGGCCCTTGTAGTCCCTACCAGTTTAGGCTGGTGGGCCCAGGGCAGTGGCCA
GGAGCCAGAAATGCCATACTGACCCAGTGGGACCGGTCGTTGAAACCCATGCAGACACGA
GTGGTCGGGAGACTTCAGAAGCCTTGCTTCTTTTTCCATTGGCTGAAGCTCTTTGCAATT
CCTATTCTGTTAATCGCTGTTTTCCTTGTGTTGACCTAA
Chromosome Location
1
Locus
1q24.3
External Identifiers
ResourceLink
UniProtKB IDP31513
UniProtKB Entry NameFMO3_HUMAN
GenBank Protein ID188631
GenBank Gene IDM83772
GeneCard IDFMO3
HGNC IDHGNC:3771
KEGG IDhsa:2328
NCBI Gene ID2328
General References
  1. Lomri N, Gu Q, Cashman JR: Molecular cloning of the flavin-containing monooxygenase (form II) cDNA from adult human liver. Proc Natl Acad Sci U S A. 1992 Mar 1;89(5):1685-9. [Article]
  2. Dolphin CT, Cullingford TE, Shephard EA, Smith RL, Phillips IR: Differential developmental and tissue-specific regulation of expression of the genes encoding three members of the flavin-containing monooxygenase family of man, FMO1, FMO3 and FM04. Eur J Biochem. 1996 Feb 1;235(3):683-9. [Article]
  3. Dolphin CT, Riley JH, Smith RL, Shephard EA, Phillips IR: Structural organization of the human flavin-containing monooxygenase 3 gene (FMO3), the favored candidate for fish-odor syndrome, determined directly from genomic DNA. Genomics. 1997 Dec 1;46(2):260-7. [Article]
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  7. Haining RL, Hunter AP, Sadeque AJ, Philpot RM, Rettie AE: Baculovirus-mediated expression and purification of human FMO3: catalytic, immunochemical, and structural characterization. Drug Metab Dispos. 1997 Jul;25(7):790-7. [Article]
  8. Treacy EP, Akerman BR, Chow LM, Youil R, Bibeau C, Lin J, Bruce AG, Knight M, Danks DM, Cashman JR, Forrest SM: Mutations of the flavin-containing monooxygenase gene (FMO3) cause trimethylaminuria, a defect in detoxication. Hum Mol Genet. 1998 May;7(5):839-45. [Article]
  9. Yeung CK, Adman ET, Rettie AE: Functional characterization of genetic variants of human FMO3 associated with trimethylaminuria. Arch Biochem Biophys. 2007 Aug 15;464(2):251-9. Epub 2007 May 2. [Article]
  10. Bian Y, Song C, Cheng K, Dong M, Wang F, Huang J, Sun D, Wang L, Ye M, Zou H: An enzyme assisted RP-RPLC approach for in-depth analysis of human liver phosphoproteome. J Proteomics. 2014 Jan 16;96:253-62. doi: 10.1016/j.jprot.2013.11.014. Epub 2013 Nov 22. [Article]
  11. Akerman BR, Forrest S, Chow L, Youil R, Knight M, Treacy EP: Two novel mutations of the FMO3 gene in a proband with trimethylaminuria. Hum Mutat. 1999;13(5):376-9. [Article]
  12. Akerman BR, Lemass H, Chow LM, Lambert DM, Greenberg C, Bibeau C, Mamer OA, Treacy EP: Trimethylaminuria is caused by mutations of the FMO3 gene in a North American cohort. Mol Genet Metab. 1999 Sep;68(1):24-31. [Article]
  13. Dolphin CT, Janmohamed A, Smith RL, Shephard EA, Phillips IR: Compound heterozygosity for missense mutations in the flavin-containing monooxygenase 3 (FM03) gene in patients with fish-odour syndrome. Pharmacogenetics. 2000 Dec;10(9):799-807. [Article]
  14. Furnes B, Feng J, Sommer SS, Schlenk D: Identification of novel variants of the flavin-containing monooxygenase gene family in African Americans. Drug Metab Dispos. 2003 Feb;31(2):187-93. [Article]
  15. Fujieda M, Yamazaki H, Togashi M, Saito T, Kamataki T: Two novel single nucleotide polymorphisms (SNPs) of the FMO3 gene in Japanese. Drug Metab Pharmacokinet. 2003;18(5):333-5. [Article]
  16. Zhang J, Tran Q, Lattard V, Cashman JR: Deleterious mutations in the flavin-containing monooxygenase 3 (FMO3) gene causing trimethylaminuria. Pharmacogenetics. 2003 Aug;13(8):495-500. [Article]
  17. Koukouritaki SB, Poch MT, Henderson MC, Siddens LK, Krueger SK, VanDyke JE, Williams DE, Pajewski NM, Wang T, Hines RN: Identification and functional analysis of common human flavin-containing monooxygenase 3 genetic variants. J Pharmacol Exp Ther. 2007 Jan;320(1):266-73. Epub 2006 Oct 18. [Article]

Associated Data

Bio-Entities
Bio-EntityType
Flavin-containing monooxygenase 3 (Humans)protein
primary
Drug Relations
DrugDrug groupPharmacological action?TypeActionsDetails
Olanzapineapproved, investigationalunknownenzymesubstrateDetails
Dapsoneapproved, investigationalunknownenzymesubstrateDetails
TamoxifenapprovedunknownenzymesubstrateDetails
VoriconazoleapprovedunknownenzymesubstrateDetails
ClozapineapprovednoenzymesubstrateDetails
Dasatinibapproved, investigationalunknownenzymesubstrateDetails
Almotriptanapproved, investigationalunknownenzymesubstrateDetails
Cimetidineapproved, investigationalunknownenzymesubstrateDetails
VandetanibapprovedunknownenzymesubstrateDetails
Neratinibapproved, investigationalunknownenzymesubstrateDetails
Propiverineapproved, investigationalunknownenzymesubstrateDetails
OlopatadineapprovednoenzymesubstrateDetails
Fedratinibapproved, investigationalunknownenzymesubstrateDetails
MethimazoleapprovedunknownenzymesubstrateDetails
UmifenovirinvestigationalunknownenzymesubstrateDetails
Risdiplamapproved, investigationalunknownenzymesubstrateDetails
Infigratinibapproved, investigationalnoenzymesubstrateDetails
Fexinidazoleapproved, investigationalunknownenzymesubstrateDetails