P31513 · FMO3_HUMAN
- ProteinFlavin-containing monooxygenase 3
- GeneFMO3
- StatusUniProtKB reviewed (Swiss-Prot)
- Organism
- Amino acids532 (go to sequence)
- Protein existenceEvidence at protein level
- Annotation score5/5
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).
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
- NADPH + O2 + trimethylamine = H2O + NADP+ + trimethylamine N-oxideThis reaction proceeds in the forward direction.
- (S)-nicotine + NADPH + O2 = H2O + NADP+ + trans-(S)-nicotine N(1')-oxideThis reaction proceeds in the forward direction.
Cofactor
Kinetics
KM | SUBSTRATE | pH | TEMPERATURE[C] | NOTES | EVIDENCE | |
---|---|---|---|---|---|---|
21 μM | trimethylamine | 8.5 | ||||
31 μM | trimethylamine | 7.4 | 37 | |||
43 μM | benzydamine | 7.4 | 37 | |||
55.7 μM | ethylenethiourea | 8.5 | ||||
71.8 μM | methimazole | 8.5 | ||||
150.1 μM | sulindac | 8.5 | ||||
248 μM | methyl p-tolyl sulfide | 7.4 | 37 |
Features
Showing features for binding site.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Binding site | 9-13 | FAD (UniProtKB | ChEBI) | ||||
Sequence: GAGVS | ||||||
Binding site | 32 | FAD (UniProtKB | ChEBI) | ||||
Sequence: E | ||||||
Binding site | 40-41 | FAD (UniProtKB | ChEBI) | ||||
Sequence: LW | ||||||
Binding site | 60-61 | NADP+ (UniProtKB | ChEBI) | ||||
Sequence: SN | ||||||
Binding site | 61-62 | FAD (UniProtKB | ChEBI) | ||||
Sequence: NS | ||||||
Binding site | 195-198 | NADP+ (UniProtKB | ChEBI) | ||||
Sequence: SGCD |
GO annotations
Aspect | Term | |
---|---|---|
Cellular Component | endoplasmic reticulum membrane | |
Cellular Component | intracellular membrane-bounded organelle | |
Molecular Function | albendazole monooxygenase activity | |
Molecular Function | flavin adenine dinucleotide binding | |
Molecular Function | hypotaurine dehydrogenase activity | |
Molecular Function | N,N-dimethylaniline monooxygenase activity | |
Molecular Function | NADP binding | |
Molecular Function | trimethylamine monooxygenase activity | |
Biological Process | taurine biosynthetic process |
Keywords
- Molecular function
- Ligand
Enzyme and pathway databases
Names & Taxonomy
Protein names
- Recommended nameFlavin-containing monooxygenase 3
- EC number
- Alternative names
Gene names
Organism names
- Organism
- Taxonomic lineageEukaryota > Metazoa > Chordata > Craniata > Vertebrata > Euteleostomi > Mammalia > Eutheria > Euarchontoglires > Primates > Haplorrhini > Catarrhini > Hominidae > Homo
Accessions
- Primary accessionP31513
- Secondary accessions
Proteomes
Organism-specific databases
Subcellular Location
UniProt Annotation
GO Annotation
Microsome membrane ; Single-pass membrane protein
Endoplasmic reticulum membrane ; Single-pass membrane protein
Features
Showing features for transmembrane.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Transmembrane | 510-530 | Helical | ||||
Sequence: FFFHWLKLFAIPILLIAVFLV |
Keywords
- Cellular component
Disease & Variants
Involvement in disease
Trimethylaminuria (TMAU)
- Note
- DescriptionInborn 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 alsoMIM:602079
Natural variants in TMAU
Variant ID | Position(s) | Change | Description | |
---|---|---|---|---|
VAR_037306 | 32 | E>K | in TMAU; dbSNP:rs72549320 | |
VAR_008146 | 52 | A>T | in TMAU; dbSNP:rs72549321 | |
VAR_037307 | 61 | N>S | in TMAU; more than 90% reduction in catalytic efficiency toward trimethylamine, benzydamine and methyl p-tolyl sulfide; dbSNP:rs72549322 | |
VAR_002423 | 66 | M>I | in TMAU; loss of activity; affects FAD binding; dbSNP:rs72549323 | |
VAR_002424 | 153 | P>L | in 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_008147 | 387 | R>L | in TMAU; dbSNP:rs72549331 | |
VAR_037308 | 434 | M>I | in TMAU; profoundly alters enzyme function; dbSNP:rs72549332 | |
VAR_008145 | 492 | R>W | in TMAU; loss of activity; affects FAD binding; dbSNP:rs72549334 |
Features
Showing features for natural variant.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Natural variant | VAR_042705 | 24 | modest increase in catalytic efficiency toward trimethylamine, methimazole, ethylenethiourea and sulindac | |||
Sequence: E → D | ||||||
Natural variant | VAR_037306 | 32 | in TMAU; dbSNP:rs72549320 | |||
Sequence: E → K | ||||||
Natural variant | VAR_008146 | 52 | in TMAU; dbSNP:rs72549321 | |||
Sequence: A → T | ||||||
Natural variant | VAR_042706 | 61 | loss of activity | |||
Sequence: N → K | ||||||
Natural variant | VAR_037307 | 61 | in TMAU; more than 90% reduction in catalytic efficiency toward trimethylamine, benzydamine and methyl p-tolyl sulfide; dbSNP:rs72549322 | |||
Sequence: N → S | ||||||
Natural variant | VAR_002423 | 66 | in TMAU; loss of activity; affects FAD binding; dbSNP:rs72549323 | |||
Sequence: M → I | ||||||
Natural variant | VAR_015364 | 132 | in dbSNP:rs12072582 | |||
Sequence: D → H | ||||||
Natural variant | VAR_002424 | 153 | in 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 | |||
Sequence: P → L | ||||||
Natural variant | VAR_002425 | 158 | 35%, 45% and 71% increase in catalytic efficiency toward trimethylamine, benzydamine and methyl p-tolyl sulfide, respectively; dbSNP:rs2266782 | |||
Sequence: E → K | ||||||
Natural variant | VAR_018345 | 198 | in dbSNP:rs529940450 | |||
Sequence: D → E | ||||||
Natural variant | VAR_018346 | 205 | in dbSNP:rs28363549 | |||
Sequence: R → C | ||||||
Natural variant | VAR_002426 | 257 | 65% increase in catalytic efficiency toward trimethylamine and 60% reduction toward benzydamine and methyl p-tolyl sulfide; dbSNP:rs1736557 | |||
Sequence: V → M | ||||||
Natural variant | VAR_014845 | 277 | in dbSNP:rs2066530 | |||
Sequence: V → A | ||||||
Natural variant | VAR_002427 | 308 | 16% reduction in catalytic efficiency toward trimethylamine and 40% increase toward benzydamine and methyl p-tolyl sulfide; dbSNP:rs2266780 | |||
Sequence: E → G | ||||||
Natural variant | VAR_015365 | 360 | in dbSNP:rs28363581 | |||
Sequence: L → P | ||||||
Natural variant | VAR_014846 | 362 | in dbSNP:rs2066532 | |||
Sequence: E → Q | ||||||
Natural variant | VAR_008147 | 387 | in TMAU; dbSNP:rs72549331 | |||
Sequence: R → L | ||||||
Natural variant | VAR_042707 | 416 | 2-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 | |||
Sequence: K → N | ||||||
Natural variant | VAR_037308 | 434 | in TMAU; profoundly alters enzyme function; dbSNP:rs72549332 | |||
Sequence: M → I | ||||||
Natural variant | VAR_008145 | 492 | in TMAU; loss of activity; affects FAD binding; dbSNP:rs72549334 | |||
Sequence: R → W | ||||||
Natural variant | VAR_015366 | 503 | in dbSNP:rs72549335 | |||
Sequence: G → R |
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.
Keywords
- Disease
Organism-specific databases
Miscellaneous
Chemistry
Genetic variation databases
PTM/Processing
Features
Showing features for initiator methionine, chain, modified residue (large scale data), modified residue.
Type | ID | Position(s) | Source | Description | |||
---|---|---|---|---|---|---|---|
Initiator methionine | 1 | UniProt | Removed | ||||
Sequence: M | |||||||
Chain | PRO_0000147654 | 2-532 | UniProt | Flavin-containing monooxygenase 3 | |||
Sequence: GKKVAIIGAGVSGLASIRSCLEEGLEPTCFEKSNDIGGLWKFSDHAEEGRASIYKSVFSNSSKEMMCFPDFPFPDDFPNFMHNSKIQEYIIAFAKEKNLLKYIQFKTFVSSVNKHPDFATTGQWDVTTERDGKKESAVFDAVMVCSGHHVYPNLPKESFPGLNHFKGKCFHSRDYKEPGVFNGKRVLVVGLGNSGCDIATELSRTAEQVMISSRSGSWVMSRVWDNGYPWDMLLVTRFGTFLKNNLPTAISDWLYVKQMNARFKHENYGLMPLNGVLRKEPVFNDELPASILCGIVSVKPNVKEFTETSAIFEDGTIFEGIDCVIFATGYSFAYPFLDESIIKSRNNEIILFKGVFPPLLEKSTIAVIGFVQSLGAAIPTVDLQSRWAAQVIKGTCTLPSMEDMMNDINEKMEKKRKWFGKSETIQTDYIVYMDELSSFIGAKPNIPWLFLTDPKLAMEVYFGPCSPYQFRLVGPGQWPGARNAILTQWDRSLKPMQTRVVGRLQKPCFFFHWLKLFAIPILLIAVFLVLT | |||||||
Modified residue (large scale data) | 20 | PRIDE | Phosphoserine | ||||
Sequence: S | |||||||
Modified residue (large scale data) | 195 | PRIDE | Phosphoserine | ||||
Sequence: S | |||||||
Modified residue | 401 | UniProt | Phosphoserine | ||||
Sequence: S |
Keywords
- PTM
Proteomic databases
PTM databases
Expression
Interaction
Binary interactions
Type | Entry 1 | Entry 2 | Number of experiments | Intact | |
---|---|---|---|---|---|
BINARY | P31513 | CLEC10A Q8IUN9 | 3 | EBI-12361463, EBI-2873246 | |
BINARY | P31513 | CREB3 O43889-2 | 4 | EBI-12361463, EBI-625022 | |
BINARY | P31513 | SACM1L Q9NTJ5 | 3 | EBI-12361463, EBI-3917235 | |
BINARY | P31513 | SGSM3 Q96HU1 | 3 | EBI-12361463, EBI-7362971 |
Protein-protein interaction databases
Miscellaneous
Structure
Sequence
- Sequence statusComplete
- Length532
- Mass (Da)60,033
- Last updated2007-01-23 v5
- Checksum729E41D53EFC4110
Computationally mapped potential isoform sequences
There are 2 potential isoforms mapped to this entry
Features
Showing features for sequence conflict.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Sequence conflict | 298 | in Ref. 1; AAA86284 | ||||
Sequence: S → T | ||||||
Sequence conflict | 369 | in Ref. 1; AAA86284 | ||||
Sequence: I → L | ||||||
Sequence conflict | 400-405 | in Ref. 1; AAA86284 | ||||
Sequence: PSMEDM → GPFYGKTL | ||||||
Sequence conflict | 410 | in Ref. 1; AAA86284 | ||||
Sequence: N → I | ||||||
Sequence conflict | 418-419 | in Ref. 1; AAA86284 | ||||
Sequence: KW → ANG | ||||||
Sequence conflict | 444-445 | in Ref. 1; AAA86284 | ||||
Sequence: KP → T | ||||||
Sequence conflict | 449 | in Ref. 1; AAA86284 | ||||
Sequence: W → M | ||||||
Sequence conflict | 454 | in Ref. 1; AAA86284 | ||||
Sequence: D → G | ||||||
Sequence conflict | 461-462 | in Ref. 1; AAA86284 | ||||
Sequence: VY → L | ||||||
Sequence conflict | 478 | in Ref. 1; AAA86284 | ||||
Sequence: Q → S | ||||||
Sequence conflict | 486 | in Ref. 2; CAA87632 | ||||
Sequence: I → M |
Keywords
- Technical term
Sequence databases
Nucleotide Sequence | Protein Sequence | Molecule Type | Status | |
---|---|---|---|---|
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 |