FMO3_BOVIN
ID FMO3_BOVIN Reviewed; 532 AA.
AC Q8HYJ9;
DT 24-JAN-2006, integrated into UniProtKB/Swiss-Prot.
DT 01-MAR-2003, sequence version 1.
DT 03-AUG-2022, entry version 119.
DE RecName: Full=Dimethylaniline monooxygenase [N-oxide-forming] 3;
DE EC=1.14.13.8 {ECO:0000250|UniProtKB:P31513};
DE EC=1.14.14.73 {ECO:0000250|UniProtKB:P31513};
DE AltName: Full=Dimethylaniline oxidase 3;
DE AltName: Full=Hepatic flavin-containing monooxygenase 3;
DE Short=FMO 3;
DE AltName: Full=Trimethylamine monooxygenase;
DE EC=1.14.13.148;
GN Name=FMO3;
OS Bos taurus (Bovine).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Laurasiatheria; Artiodactyla; Ruminantia; Pecora; Bovidae;
OC Bovinae; Bos.
OX NCBI_TaxID=9913;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, AND DISEASE.
RX PubMed=12466292; DOI=10.1101/gr.240202;
RA Lunden A., Marklund S., Gustafsson V., Andersson L.;
RT "A nonsense mutation in the FMO3 gene underlies fishy off-flavor in cow's
RT milk.";
RL Genome Res. 12:1885-1888(2002).
CC -!- FUNCTION: Essential hepatic enzyme that catalyzes the oxygenation of a
CC wide variety of nitrogen- and sulfur-containing compounds including
CC drugs as well as dietary compounds. Plays an important role in the
CC metabolism of trimethylamine (TMA), via the production of
CC trimethylamine N-oxide (TMAO) metabolite. TMA is generated by the
CC action of gut microbiota using dietary precursors such as choline,
CC choline containing compounds, betaine or L-carnitine. By regulating
CC TMAO concentration, FMO3 directly impacts both platelet responsiveness
CC and rate of thrombus formation. {ECO:0000250|UniProtKB:P31513,
CC ECO:0000250|UniProtKB:P97501}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=H(+) + N,N-dimethylaniline + NADPH + O2 = H2O + N,N-
CC dimethylaniline N-oxide + NADP(+); Xref=Rhea:RHEA:24468,
CC ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:15379,
CC ChEBI:CHEBI:16269, ChEBI:CHEBI:17735, ChEBI:CHEBI:57783,
CC ChEBI:CHEBI:58349; EC=1.14.13.8;
CC Evidence={ECO:0000250|UniProtKB:P31513};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=NADPH + O2 + trimethylamine = H2O + NADP(+) + trimethylamine
CC N-oxide; Xref=Rhea:RHEA:31979, ChEBI:CHEBI:15377, ChEBI:CHEBI:15379,
CC ChEBI:CHEBI:15724, ChEBI:CHEBI:57783, ChEBI:CHEBI:58349,
CC ChEBI:CHEBI:58389; EC=1.14.13.148;
CC Evidence={ECO:0000250|UniProtKB:P31513};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=fenbendazole + O2 + reduced [NADPH--hemoprotein reductase] =
CC fenbendazole S-oxide + H(+) + H2O + oxidized [NADPH--hemoprotein
CC reductase]; Xref=Rhea:RHEA:55928, Rhea:RHEA-COMP:11964, Rhea:RHEA-
CC COMP:11965, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:15379,
CC ChEBI:CHEBI:35812, ChEBI:CHEBI:57618, ChEBI:CHEBI:58210,
CC ChEBI:CHEBI:77092; EC=1.14.14.73;
CC Evidence={ECO:0000250|UniProtKB:P31513};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=albendazole + O2 + reduced [NADPH--hemoprotein reductase] =
CC albendazole S-oxide + H(+) + H2O + oxidized [NADPH--hemoprotein
CC reductase]; Xref=Rhea:RHEA:55924, Rhea:RHEA-COMP:11964, Rhea:RHEA-
CC COMP:11965, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:15379,
CC ChEBI:CHEBI:16664, ChEBI:CHEBI:16959, ChEBI:CHEBI:57618,
CC ChEBI:CHEBI:58210; EC=1.14.14.73;
CC Evidence={ECO:0000250|UniProtKB:P31513};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=(S)-nicotine + NADPH + O2 = H2O + NADP(+) + trans-(S)-nicotine
CC N(1')-oxide; Xref=Rhea:RHEA:58720, ChEBI:CHEBI:15377,
CC ChEBI:CHEBI:15379, ChEBI:CHEBI:57783, ChEBI:CHEBI:58349,
CC ChEBI:CHEBI:59806, ChEBI:CHEBI:142660;
CC Evidence={ECO:0000250|UniProtKB:P31513};
CC -!- COFACTOR:
CC Name=FAD; Xref=ChEBI:CHEBI:57692; Evidence={ECO:0000250};
CC -!- SUBCELLULAR LOCATION: Microsome membrane
CC {ECO:0000250|UniProtKB:P32417}; Single-pass membrane protein
CC {ECO:0000255}. Endoplasmic reticulum membrane
CC {ECO:0000250|UniProtKB:P32417}; Single-pass membrane protein
CC {ECO:0000255}.
CC -!- DISEASE: Note=Defects in FMO3 are the cause of a fishy off-flavor in
CC cow milk due to by an elevated level of trimethylamine (TMA) in body
CC fluids. {ECO:0000269|PubMed:12466292}.
CC -!- SIMILARITY: Belongs to the FMO family. {ECO:0000305}.
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DR EMBL; AF488422; AAN27919.1; -; mRNA.
DR RefSeq; NP_776482.1; NM_174057.2.
DR AlphaFoldDB; Q8HYJ9; -.
DR SMR; Q8HYJ9; -.
DR STRING; 9913.ENSBTAP00000027444; -.
DR PaxDb; Q8HYJ9; -.
DR PeptideAtlas; Q8HYJ9; -.
DR PRIDE; Q8HYJ9; -.
DR Ensembl; ENSBTAT00000027444; ENSBTAP00000027444; ENSBTAG00000020597.
DR GeneID; 281167; -.
DR KEGG; bta:281167; -.
DR CTD; 2328; -.
DR VEuPathDB; HostDB:ENSBTAG00000020597; -.
DR VGNC; VGNC:29051; FMO3.
DR eggNOG; KOG1399; Eukaryota.
DR GeneTree; ENSGT00940000161339; -.
DR HOGENOM; CLU_006909_8_2_1; -.
DR InParanoid; Q8HYJ9; -.
DR OMA; SIPWLFL; -.
DR OrthoDB; 405736at2759; -.
DR TreeFam; TF105285; -.
DR Proteomes; UP000009136; Chromosome 16.
DR Bgee; ENSBTAG00000020597; Expressed in metanephros cortex and 69 other tissues.
DR ExpressionAtlas; Q8HYJ9; baseline and differential.
DR GO; GO:0005789; C:endoplasmic reticulum membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0016021; C:integral component of membrane; IEA:UniProtKB-KW.
DR GO; GO:0050660; F:flavin adenine dinucleotide binding; IEA:InterPro.
DR GO; GO:0004497; F:monooxygenase activity; IBA:GO_Central.
DR GO; GO:0004499; F:N,N-dimethylaniline monooxygenase activity; IEA:UniProtKB-EC.
DR GO; GO:0050661; F:NADP binding; IEA:InterPro.
DR GO; GO:0034899; F:trimethylamine monooxygenase activity; IEA:UniProtKB-EC.
DR Gene3D; 3.50.50.60; -; 4.
DR InterPro; IPR036188; FAD/NAD-bd_sf.
DR InterPro; IPR000960; Flavin_mOase.
DR InterPro; IPR020946; Flavin_mOase-like.
DR InterPro; IPR002255; Flavin_mOase_3.
DR Pfam; PF00743; FMO-like; 1.
DR PIRSF; PIRSF000332; FMO; 1.
DR PRINTS; PR00370; FMOXYGENASE.
DR PRINTS; PR01123; FMOXYGENASE3.
DR SUPFAM; SSF51905; SSF51905; 2.
PE 2: Evidence at transcript level;
KW Endoplasmic reticulum; FAD; Flavoprotein; Membrane; Microsome;
KW Monooxygenase; NADP; Oxidoreductase; Phosphoprotein; Reference proteome;
KW Transmembrane; Transmembrane helix.
FT CHAIN 1..532
FT /note="Dimethylaniline monooxygenase [N-oxide-forming] 3"
FT /id="PRO_0000147652"
FT TRANSMEM 510..530
FT /note="Helical"
FT /evidence="ECO:0000255"
FT BINDING 9..13
FT /ligand="FAD"
FT /ligand_id="ChEBI:CHEBI:57692"
FT /evidence="ECO:0000250|UniProtKB:Q9HFE4"
FT BINDING 32
FT /ligand="FAD"
FT /ligand_id="ChEBI:CHEBI:57692"
FT /evidence="ECO:0000250|UniProtKB:Q9HFE4"
FT BINDING 40..41
FT /ligand="FAD"
FT /ligand_id="ChEBI:CHEBI:57692"
FT /evidence="ECO:0000250|UniProtKB:Q9HFE4"
FT BINDING 60..61
FT /ligand="NADP(+)"
FT /ligand_id="ChEBI:CHEBI:58349"
FT /evidence="ECO:0000250|UniProtKB:Q9HFE4"
FT BINDING 61..62
FT /ligand="FAD"
FT /ligand_id="ChEBI:CHEBI:57692"
FT /evidence="ECO:0000250|UniProtKB:Q9HFE4"
FT BINDING 195..198
FT /ligand="NADP(+)"
FT /ligand_id="ChEBI:CHEBI:58349"
FT /evidence="ECO:0000250|UniProtKB:Q9HFE4"
FT MOD_RES 401
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P97501"
SQ SEQUENCE 532 AA; 60093 MW; 2CA5964889490CBA CRC64;
MVKKVAIIGA GISGLASIRN CLEEGLEPTC FEKGEDIGGL WKFSDHVEEG RASIYRSVFT
NSSKEMTCFP DFPFPDDFPN FMHNSKLQEY ITMFAKEKNL LKYIQFKTIV SSVNKRPDFQ
TTGQWDVITE KDGKKESAVF DAVMICSGHH VYPNIPKESF PGIKLFKGKC FHSRDYKEPG
IFKGKRVLVI GLGNSGCDIA SELSHIAEKV IISSRSGSWV MSRVWDEGYP WDMLFITRFE
TFLKNTLPTV ISNWWYMKQM NARFKHENYG LMPLNSTLRK EPVFNDELPA CILCGIVTIK
PNVKEFTEDS AIFEDGTVFK AIDYVIFATG YSYAYPFLDD SIIKSRDNEV TLFKGIFPPP
LEKPTLAVIG LVQSLGAAIP TTDLQSRWAV QVIKGTCPLP SVKDMMNDID EKMGKKLKLF
GKSDTIQTDY VVYMDELASF IGAKPNIPWL FLTDPKLALE VYFGPCTPYQ FRLVGPGKWP
GARNAILTQW DRLLKPMTTR VVGSPLKPCL FCNWFRPVLI SVVSIAALIV LF
