ID   FMO3_RABIT              Reviewed;         531 AA.
AC   P32417;
DT   01-OCT-1993, integrated into UniProtKB/Swiss-Prot.
DT   23-JAN-2007, sequence version 3.
DT   04-NOV-2026, entry version 144.
DE   RecName: Full=Flavin-containing monooxygenase 3 {ECO:0000250|UniProtKB:P31513};
DE            EC=1.14.13.148 {ECO:0000250|UniProtKB:P31513};
DE            EC=1.14.13.32 {ECO:0000250|UniProtKB:P31513};
DE            EC=1.14.13.8 {ECO:0000250|UniProtKB:P31513};
DE   AltName: Full=Dimethylaniline monooxygenase [N-oxide-forming] 3;
DE   AltName: Full=Dimethylaniline oxidase 3;
DE   AltName: Full=FMO 1D1;
DE   AltName: Full=FMO II;
DE   AltName: Full=FMO form 2 {ECO:0000303|PubMed:8142375};
DE   AltName: Full=Hepatic flavin-containing monooxygenase 3;
DE            Short=FMO 3;
DE   AltName: Full=Trimethylamine monooxygenase;
GN   Name=FMO3;
OS   Oryctolagus cuniculus (Rabbit).
OC   Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC   Eutheria; Euarchontoglires; Glires; Lagomorpha; Leporidae; Oryctolagus.
OX   NCBI_TaxID=9986;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [MRNA].
RC   STRAIN=New Zealand white; TISSUE=Liver;
RX   PubMed=8188717; DOI=10.1016/s0021-9258(17)36791-1;
RA   Burnett V.L., Lawton M.P., Philpot R.M.;
RT   "Cloning and sequencing of flavin-containing monooxygenases FMO3 and FMO4
RT   from rabbit and characterization of FMO3.";
RL   J. Biol. Chem. 269:14314-14322(1994).
RN   [2]
RP   PROTEIN SEQUENCE OF 2-531.
RX   PubMed=1898080; DOI=10.1016/0003-9861(91)90596-b;
RA   Ozols J.;
RT   "Multiple forms of liver microsomal flavin-containing monooxygenases:
RT   complete covalent structure of form 2.";
RL   Arch. Biochem. Biophys. 290:103-115(1991).
RN   [3]
RP   PROTEIN SEQUENCE OF 2-531, AND SUBCELLULAR LOCATION.
RC   STRAIN=New Zealand white; TISSUE=Liver;
RX   PubMed=8142375; DOI=10.1021/bi00178a035;
RA   Ozols J.;
RT   "Isolation and structure of a third form of liver microsomal flavin
RT   monooxygenase.";
RL   Biochemistry 33:3751-3757(1994).
RN   [4]
RP   PROTEIN SEQUENCE OF 2-33, TISSUE SPECIFICITY, AND SUBCELLULAR LOCATION.
RC   TISSUE=Liver;
RX   PubMed=2505769; DOI=10.1016/0006-291x(89)92097-4;
RA   Ozols J.;
RT   "Liver microsomes contain two distinct NADPH-Monooxygenases with NH2-
RT   terminal segments homologous to the flavin containing NADPH-monooxygenase
RT   of Pseudomonas fluorescens.";
RL   Biochem. Biophys. Res. Commun. 163:49-55(1989).
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   -!- CATALYTIC ACTIVITY:
CC       Reaction=trimethylamine + NADPH + O2 = trimethylamine N-oxide + NADP(+)
CC         + H2O; 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       PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:31980;
CC         Evidence={ECO:0000250|UniProtKB:P31513};
CC   -!- CATALYTIC ACTIVITY:
CC       Reaction=N,N-dimethylaniline + NADPH + O2 + H(+) = N,N-dimethylaniline
CC         N-oxide + NADP(+) + H2O; Xref=Rhea:RHEA:24468, ChEBI:CHEBI:15377,
CC         ChEBI:CHEBI:15378, ChEBI:CHEBI:15379, ChEBI:CHEBI:16269,
CC         ChEBI:CHEBI:17735, ChEBI:CHEBI:57783, ChEBI:CHEBI:58349;
CC         EC=1.14.13.8; Evidence={ECO:0000250|UniProtKB:P31513};
CC       PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:24469;
CC         Evidence={ECO:0000250|UniProtKB:P31513};
CC   -!- CATALYTIC ACTIVITY:
CC       Reaction=hypotaurine + NADPH + O2 + H(+) = taurine + NADP(+) + H2O;
CC         Xref=Rhea:RHEA:69819, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378,
CC         ChEBI:CHEBI:15379, ChEBI:CHEBI:57783, ChEBI:CHEBI:57853,
CC         ChEBI:CHEBI:58349, ChEBI:CHEBI:507393; EC=1.14.13.8;
CC         Evidence={ECO:0000250|UniProtKB:P31513};
CC       PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:69820;
CC         Evidence={ECO:0000250|UniProtKB:P31513};
CC   -!- CATALYTIC ACTIVITY:
CC       Reaction=(S)-nicotine + NADPH + O2 = trans-(S)-nicotine N(1')-oxide +
CC         NADP(+) + H2O; 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       PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:58721;
CC         Evidence={ECO:0000250|UniProtKB:P31513};
CC   -!- CATALYTIC ACTIVITY:
CC       Reaction=albendazole + NADPH + O2 + H(+) = albendazole S-oxide +
CC         NADP(+) + H2O; Xref=Rhea:RHEA:10796, ChEBI:CHEBI:15377,
CC         ChEBI:CHEBI:15378, ChEBI:CHEBI:15379, ChEBI:CHEBI:16664,
CC         ChEBI:CHEBI:16959, ChEBI:CHEBI:57783, ChEBI:CHEBI:58349;
CC         EC=1.14.13.32; Evidence={ECO:0000250|UniProtKB:P31513};
CC       PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:10797;
CC         Evidence={ECO:0000250|UniProtKB:P31513};
CC   -!- COFACTOR:
CC       Name=FAD; Xref=ChEBI:CHEBI:57692;
CC   -!- SUBCELLULAR LOCATION: Microsome membrane {ECO:0000269|PubMed:2505769,
CC       ECO:0000269|PubMed:8142375}; Single-pass membrane protein
CC       {ECO:0000255}. Endoplasmic reticulum membrane
CC       {ECO:0000305|PubMed:2505769}; Single-pass membrane protein
CC       {ECO:0000255}.
CC   -!- TISSUE SPECIFICITY: Liver. {ECO:0000269|PubMed:2505769}.
CC   -!- SIMILARITY: Belongs to the FMO family. {ECO:0000305}.
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DR   EMBL; L10391; AAA21178.1; -; mRNA.
DR   PIR; B54096; B54096.
DR   PIR; S18380; S18380.
DR   RefSeq; NP_001075715.1; NM_001082246.1.
DR   RefSeq; XP_008262186.1; XM_008263964.4.
DR   SMR; P32417; -.
DR   STRING; 9986.ENSOCUP00000003129; -.
DR   PaxDb; 9986-ENSOCUP00000003129; -.
DR   Ensembl; ENSOCUT00000003608.2; ENSOCUP00000003129.2; ENSOCUG00000003610.4.
DR   GeneID; 100009065; -.
DR   KEGG; ocu:100009065; -.
DR   CTD; 2328; -.
DR   eggNOG; KOG1399; Eukaryota.
DR   GeneTree; ENSGT00940000161339; -.
DR   HOGENOM; CLU_006909_8_2_1; -.
DR   InParanoid; P32417; -.
DR   OMA; AAISKVW; -.
DR   OrthoDB; 66881at2759; -.
DR   BRENDA; 1.14.13.148; 1749.
DR   Bgee; ENSOCUG00000003610; Expressed in liver and 12 other cell types or tissues.
DR   FunFam; 3.50.50.60:FF:000023; Dimethylaniline monooxygenase [N-oxide-forming]; 1.
DR   FunFam; 3.50.50.60:FF:000073; Dimethylaniline monooxygenase [N-oxide-forming]; 1.
DR   FunFam; 3.50.50.60:FF:000279; Dimethylaniline monooxygenase [N-oxide-forming]; 1.
DR   FunFam; 3.50.50.60:FF:000454; Dimethylaniline monooxygenase [N-oxide-forming]; 1.
DR   Gene3D; 3.50.50.60; FAD/NAD(P)-binding domain; 2.
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   InterPro; IPR050346; FMO-like.
DR   PANTHER; PTHR23023; DIMETHYLANILINE MONOOXYGENASE; 1.
DR   Pfam; PF00743; FMO-like; 1.
DR   PIRSF; PIRSF000332; FMO; 1.
DR   PRINTS; PR00370; FMOXYGENASE.
DR   PRINTS; PR01123; FMOXYGENASE3.
DR   SUPFAM; SSF51905; FAD/NAD(P)-binding domain; 2.
DR   GO; GO:0005789; C:endoplasmic reticulum membrane; IEA:UniProtKB-SubCell.
DR   GO; GO:0047638; F:albendazole monooxygenase activity; ISS:UniProtKB.
DR   GO; GO:0050660; F:flavin adenine dinucleotide binding; IEA:InterPro.
DR   GO; GO:0047822; F:hypotaurine monooxygenase activity; ISS:UniProtKB.
DR   GO; GO:0004499; F:N,N-dimethylaniline monooxygenase activity; ISS:UniProtKB.
DR   GO; GO:0050661; F:NADP binding; IEA:InterPro.
DR   GO; GO:0034899; F:trimethylamine monooxygenase activity; ISS:UniProtKB.
DR   GO; GO:0042412; P:taurine biosynthetic process; IEA:Ensembl.
DR   GO; GO:0006805; P:xenobiotic metabolic process; IEA:UniProtKB-ARBA.
DR   Proteomes; UP000001811; Chromosome 13.
DR   AlphaFoldDB; P32417; -.
DR   FunCoup; P32417; 387.
PE   1: Evidence at protein level;
KW   Direct protein sequencing; Endoplasmic reticulum; FAD; Flavoprotein;
KW   Membrane; Microsome; Monooxygenase; NADP; Oxidoreductase;
KW   Reference proteome; Transmembrane; Transmembrane helix.
FT   INIT_MET        1
FT                   /note="Removed"
FT                   /evidence="ECO:0000269|PubMed:1898080,
FT                   ECO:0000269|PubMed:2505769"
FT   CHAIN           2..531
FT                   /note="Flavin-containing monooxygenase 3"
FT                   /id="PRO_0000147658"
FT   TRANSMEM        511..531
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   VARIANT         279
FT                   /note="R -> M"
FT   VARIANT         405
FT                   /note="M -> V"
FT   CONFLICT        76
FT                   /note="D -> P (in Ref. 2; AA sequence)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        81
FT                   /note="F -> N (in Ref. 2; AA sequence)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        128..130
FT                   /note="STE -> ATC (in Ref. 2; AA sequence)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        172..173
FT                   /note="HS -> RQ (in Ref. 2; AA sequence)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        197
FT                   /note="C -> E (in Ref. 2; AA sequence)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        306
FT                   /note="F -> FKEF (in Ref. 2; AA sequence)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        419
FT                   /note="W -> T (in Ref. 2; AA sequence)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        423
FT                   /note="S -> W (in Ref. 2; AA sequence)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        514..516
FT                   /note="WLK -> ELW (in Ref. 2; AA sequence)"
FT                   /evidence="ECO:0000305"
SQ   SEQUENCE   531 AA;  59815 MW;  A4505481077C6CC8 CRC64;
     MGKKVAIIGA GISGLASIRS CLEEGLEPTC FEMSDDIGGL WKFSDHAEEG RASIYQSVFT
     NSSKEMMCFP DFPFPDDFPN FMHNSKLQEY ITTFAREKNL LKYIQFKTLV SSIKKHPDFS
     VTGQWYVSTE RNGKKETAVF DAVMICSGHH VYPNLPKDSF PGLKHFKGKS FHSREYKEPG
     IFKGKRVLVI GLGNSGCDIA TELSHTAEQV VISSRSGSWV MSRVWDDGYP WDMLYVTRFQ
     TFLKNNLPTA ISDWWYVKQM NAKFKHENYS LMPLNGTLRK EPVFNDDLPA RILCGTVSIK
     PNVKEFTETS AIFEDGTVFE AIDSVIFATG YGYAYPFLDD SIIKSENNKV TLFKGIFPPQ
     LEKPTMAVIG LVQSLGAAIP TTDLQARWAA QVIKGTCTLP PVKDMMNDIH EKMGTKLKWF
     GKSETIQTDY INYMDELASF IGVKLNIPWL FLTDPRLALE VFFGPCSPYQ FRLVGPGKWP
     GARQAILTQW DRSLKPMKTR AVGHLQKPAL FSPWLKLLAI AVLLIAAVLV F
//