Dimethylaniline monooxygenase [N-oxide-forming] 3

Details

Name
Dimethylaniline monooxygenase [N-oxide-forming] 3
Synonyms
  • 1.14.13.8
  • Dimethylaniline oxidase 3
  • FMO 3
  • FMO form 2
  • FMO II
  • Hepatic flavin-containing monooxygenase 3
  • Trimethylamine monooxygenase
Gene Name
FMO3
Organism
Humans
Amino acid sequence
>lcl|BSEQ0012507|Dimethylaniline monooxygenase [N-oxide-forming] 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
flavin adenine dinucleotide binding / N,N-dimethylaniline monooxygenase activity / NADP binding / trimethylamine monooxygenase activity
Processes
drug metabolic process / oxidation-reduction process / small molecule metabolic process / xenobiotic metabolic process
Components
endoplasmic reticulum membrane / integral component of membrane / intracellular membrane-bounded organelle
General Function
Trimethylamine monooxygenase activity
Specific 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 (PubMed:9224773).
Pfam Domain Function
Transmembrane Regions
Not Available
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
1q23-q25
External Identifiers
ResourceLink
UniProtKB IDP31513
UniProtKB Entry NameFMO3_HUMAN
GenBank Protein ID188631
GenBank Gene IDM83772
HGNC IDHGNC:3771
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. [PubMed:1542660]
  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. [PubMed:8654418]
  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. [PubMed:9417913]
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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. [PubMed:9224773]
  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. [PubMed:9536088]
  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. [PubMed:17531949]
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  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. [PubMed:10479479]
  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. [PubMed:11191884]
  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. [PubMed:12527699]
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Drug Relations

Drug Relations
DrugBank IDNameDrug groupPharmacological action?ActionsDetails
DB00334Olanzapineapproved, investigationalunknownsubstrateDetails
DB00250Dapsoneapproved, investigationalunknownsubstrateDetails
DB00675TamoxifenapprovedunknownsubstrateDetails
DB00582Voriconazoleapproved, investigationalunknownsubstrateDetails
DB00363ClozapineapprovedunknownsubstrateDetails
DB01254Dasatinibapproved, investigationalunknownsubstrateDetails
DB00918Almotriptanapproved, investigationalunknownsubstrateDetails
DB00501Cimetidineapproved, investigationalunknownsubstrateDetails
DB05294VandetanibapprovedunknownsubstrateDetails
DB11828Neratinibapproved, investigationalunknownsubstrateDetails
DB12278Propiverineapproved, investigationalunknownsubstrateDetails