P31513 · FMO3_HUMAN

  • Protein
    Flavin-containing monooxygenase 3
  • Gene
    FMO3
  • Status
    UniProtKB reviewed (Swiss-Prot)
  • Amino acids
  • Protein existence
    Evidence at protein level
  • Annotation score
    5/5

Function

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).

Catalytic activity

Cofactor

FAD (UniProtKB | Rhea| CHEBI:57692 )

Kinetics

KM SUBSTRATE pH TEMPERATURE[C] NOTES EVIDENCE
21 μMtrimethylamine8.5
31 μMtrimethylamine7.437
43 μMbenzydamine7.437
55.7 μMethylenethiourea8.5
71.8 μMmethimazole8.5
150.1 μMsulindac8.5
248 μMmethyl p-tolyl sulfide7.437

Features

Showing features for binding site.

TypeIDPosition(s)Description
Binding site9-13FAD (UniProtKB | ChEBI)
Binding site32FAD (UniProtKB | ChEBI)
Binding site40-41FAD (UniProtKB | ChEBI)
Binding site60-61NADP+ (UniProtKB | ChEBI)
Binding site61-62FAD (UniProtKB | ChEBI)
Binding site195-198NADP+ (UniProtKB | ChEBI)

GO annotations

AspectTerm
Cellular Componentendoplasmic reticulum membrane
Cellular Componentintracellular membrane-bounded organelle
Molecular Functionalbendazole monooxygenase activity
Molecular Functionflavin adenine dinucleotide binding
Molecular Functionhypotaurine dehydrogenase activity
Molecular FunctionN,N-dimethylaniline monooxygenase activity
Molecular FunctionNADP binding
Molecular Functiontrimethylamine monooxygenase activity
Biological Processtaurine biosynthetic process

Keywords

Enzyme and pathway databases

Names & Taxonomy

Protein names

  • Recommended name
    Flavin-containing monooxygenase 3
  • EC number
  • Alternative names
    • Dimethylaniline monooxygenase [N-oxide-forming] 3
    • Dimethylaniline oxidase 3
    • FMO II
    • FMO form 2
    • Hepatic flavin-containing monooxygenase 3 (FMO 3)
    • Trimethylamine monooxygenase

Gene names

    • Name
      FMO3

Organism names

  • Taxonomic identifier
  • Taxonomic lineage
    Eukaryota > Metazoa > Chordata > Craniata > Vertebrata > Euteleostomi > Mammalia > Eutheria > Euarchontoglires > Primates > Haplorrhini > Catarrhini > Hominidae > Homo

Accessions

  • Primary accession
    P31513
  • Secondary accessions
    • B2R816
    • Q14854
    • Q8N5N5

Proteomes

Organism-specific databases

Subcellular Location

Microsome membrane
; Single-pass membrane protein
Endoplasmic reticulum membrane
; Single-pass membrane protein

Features

Showing features for transmembrane.

TypeIDPosition(s)Description
Transmembrane510-530Helical

Keywords

Disease & Variants

Involvement in disease

Trimethylaminuria (TMAU)

  • Note
    • The disease is caused by variants affecting the gene represented in this entry
  • Description
    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. Affected 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.
  • See also
    MIM:602079
Natural variants in TMAU
Variant IDPosition(s)ChangeDescription
VAR_03730632E>Kin TMAU; dbSNP:rs72549320
VAR_00814652A>Tin TMAU; dbSNP:rs72549321
VAR_03730761N>Sin TMAU; more than 90% reduction in catalytic efficiency toward trimethylamine, benzydamine and methyl p-tolyl sulfide; dbSNP:rs72549322
VAR_00242366M>Iin TMAU; loss of activity; affects FAD binding; dbSNP:rs72549323
VAR_002424153P>Lin TMAU; 90% reduction in catalytic efficiency toward trimethylamine and benzydamine; 34% reduction in catalytic efficiency toward methyl p-tolyl sulfide; nearly no effect on affinity for these substrates; dbSNP:rs72549326
VAR_008147387R>Lin TMAU; dbSNP:rs72549331
VAR_037308434M>Iin TMAU; profoundly alters enzyme function; dbSNP:rs72549332
VAR_008145492R>Win TMAU; loss of activity; affects FAD binding; dbSNP:rs72549334

Features

Showing features for natural variant.

TypeIDPosition(s)Description
Natural variantVAR_04270524modest increase in catalytic efficiency toward trimethylamine, methimazole, ethylenethiourea and sulindac
Natural variantVAR_03730632in TMAU; dbSNP:rs72549320
Natural variantVAR_00814652in TMAU; dbSNP:rs72549321
Natural variantVAR_04270661loss of activity
Natural variantVAR_03730761in TMAU; more than 90% reduction in catalytic efficiency toward trimethylamine, benzydamine and methyl p-tolyl sulfide; dbSNP:rs72549322
Natural variantVAR_00242366in TMAU; loss of activity; affects FAD binding; dbSNP:rs72549323
Natural variantVAR_015364132in dbSNP:rs12072582
Natural variantVAR_002424153in TMAU; 90% reduction in catalytic efficiency toward trimethylamine and benzydamine; 34% reduction in catalytic efficiency toward methyl p-tolyl sulfide; nearly no effect on affinity for these substrates; dbSNP:rs72549326
Natural variantVAR_00242515835%, 45% and 71% increase in catalytic efficiency toward trimethylamine, benzydamine and methyl p-tolyl sulfide, respectively; dbSNP:rs2266782
Natural variantVAR_018345198in dbSNP:rs529940450
Natural variantVAR_018346205in dbSNP:rs28363549
Natural variantVAR_00242625765% increase in catalytic efficiency toward trimethylamine and 60% reduction toward benzydamine and methyl p-tolyl sulfide; dbSNP:rs1736557
Natural variantVAR_014845277in dbSNP:rs2066530
Natural variantVAR_00242730816% reduction in catalytic efficiency toward trimethylamine and 40% increase toward benzydamine and methyl p-tolyl sulfide; dbSNP:rs2266780
Natural variantVAR_015365360in dbSNP:rs28363581
Natural variantVAR_014846362in dbSNP:rs2066532
Natural variantVAR_008147387in TMAU; dbSNP:rs72549331
Natural variantVAR_0427074162-fold decrease in affinity for trimethylamine; 3-fold decrease in catalytic efficiency toward methimazole; 3-fold increase in catalytic efficiency toward sulindac; 30% increase in catalytic efficiency toward ethylenethiourea; dbSNP:rs774785217
Natural variantVAR_037308434in TMAU; profoundly alters enzyme function; dbSNP:rs72549332
Natural variantVAR_008145492in TMAU; loss of activity; affects FAD binding; dbSNP:rs72549334
Natural variantVAR_015366503in dbSNP:rs72549335

Variants

We now provide the "Disease & Variants" viewer in its own tab.

The viewer provides 738 variants from UniProt as well as other sources including ClinVar and dbSNP.

Go to variant viewer

Keywords

Organism-specific databases

Miscellaneous

Chemistry

Genetic variation databases

PTM/Processing

Features

Showing features for initiator methionine, chain, modified residue (large scale data), modified residue.

TypeIDPosition(s)SourceDescription
Initiator methionine1UniProtRemoved
ChainPRO_00001476542-532UniProtFlavin-containing monooxygenase 3
Modified residue (large scale data)20PRIDEPhosphoserine
Modified residue (large scale data)195PRIDEPhosphoserine
Modified residue401UniProtPhosphoserine

Keywords

Proteomic databases

PTM databases

Expression

Tissue specificity

Liver.

Gene expression databases

Organism-specific databases

Interaction

Binary interactions

Protein-protein interaction databases

Miscellaneous

Structure

Family & Domains

Sequence similarities

Belongs to the FMO family.

Keywords

Phylogenomic databases

Family and domain databases

Sequence

  • Sequence status
    Complete
  • Length
    532
  • Mass (Da)
    60,033
  • Last updated
    2007-01-23 v5
  • Checksum
    729E41D53EFC4110
MGKKVAIIGAGVSGLASIRSCLEEGLEPTCFEKSNDIGGLWKFSDHAEEGRASIYKSVFSNSSKEMMCFPDFPFPDDFPNFMHNSKIQEYIIAFAKEKNLLKYIQFKTFVSSVNKHPDFATTGQWDVTTERDGKKESAVFDAVMVCSGHHVYPNLPKESFPGLNHFKGKCFHSRDYKEPGVFNGKRVLVVGLGNSGCDIATELSRTAEQVMISSRSGSWVMSRVWDNGYPWDMLLVTRFGTFLKNNLPTAISDWLYVKQMNARFKHENYGLMPLNGVLRKEPVFNDELPASILCGIVSVKPNVKEFTETSAIFEDGTIFEGIDCVIFATGYSFAYPFLDESIIKSRNNEIILFKGVFPPLLEKSTIAVIGFVQSLGAAIPTVDLQSRWAAQVIKGTCTLPSMEDMMNDINEKMEKKRKWFGKSETIQTDYIVYMDELSSFIGAKPNIPWLFLTDPKLAMEVYFGPCSPYQFRLVGPGQWPGARNAILTQWDRSLKPMQTRVVGRLQKPCFFFHWLKLFAIPILLIAVFLVLT

Computationally mapped potential isoform sequences

There are 2 potential isoforms mapped to this entry

View all
EntryEntry nameGene nameLength
V9GYP3V9GYP3_HUMANFMO348
V9GZ60V9GZ60_HUMANFMO3218

Features

Showing features for sequence conflict.

TypeIDPosition(s)Description
Sequence conflict298in Ref. 1; AAA86284
Sequence conflict369in Ref. 1; AAA86284
Sequence conflict400-405in Ref. 1; AAA86284
Sequence conflict410in Ref. 1; AAA86284
Sequence conflict418-419in Ref. 1; AAA86284
Sequence conflict444-445in Ref. 1; AAA86284
Sequence conflict449in Ref. 1; AAA86284
Sequence conflict454in Ref. 1; AAA86284
Sequence conflict461-462in Ref. 1; AAA86284
Sequence conflict478in Ref. 1; AAA86284
Sequence conflict486in Ref. 2; CAA87632

Keywords

Sequence databases

Nucleotide SequenceProtein SequenceMolecule TypeStatus
M83772
EMBL· GenBank· DDBJ
AAA86284.1
EMBL· GenBank· DDBJ
mRNA
Z47552
EMBL· GenBank· DDBJ
CAA87632.1
EMBL· GenBank· DDBJ
mRNA
U39967
EMBL· GenBank· DDBJ
AAC51932.1
EMBL· GenBank· DDBJ
Genomic DNA
U39961
EMBL· GenBank· DDBJ
AAC51932.1
EMBL· GenBank· DDBJ
Genomic DNA
U39962
EMBL· GenBank· DDBJ
AAC51932.1
EMBL· GenBank· DDBJ
Genomic DNA
U39963
EMBL· GenBank· DDBJ
AAC51932.1
EMBL· GenBank· DDBJ
Genomic DNA
U39964
EMBL· GenBank· DDBJ
AAC51932.1
EMBL· GenBank· DDBJ
Genomic DNA
U39965
EMBL· GenBank· DDBJ
AAC51932.1
EMBL· GenBank· DDBJ
Genomic DNA
U39966
EMBL· GenBank· DDBJ
AAC51932.1
EMBL· GenBank· DDBJ
Genomic DNA
AY895830
EMBL· GenBank· DDBJ
AAW65372.1
EMBL· GenBank· DDBJ
Genomic DNA
AK313197
EMBL· GenBank· DDBJ
BAG36013.1
EMBL· GenBank· DDBJ
mRNA
AL021026
EMBL· GenBank· DDBJ
-Genomic DNA No translation available.
CH471067
EMBL· GenBank· DDBJ
EAW90887.1
EMBL· GenBank· DDBJ
Genomic DNA
BC032016
EMBL· GenBank· DDBJ
AAH32016.1
EMBL· GenBank· DDBJ
mRNA

Genome annotation databases

Similar Proteins

Disclaimer

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