FMO3_RABIT
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 03-AUG-2022, entry version 131.
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=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;
DE EC=1.14.13.148;
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 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;
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_008263964.2.
DR AlphaFoldDB; P32417; -.
DR SMR; P32417; -.
DR STRING; 9986.ENSOCUP00000026249; -.
DR PRIDE; P32417; -.
DR Ensembl; ENSOCUT00000003608; ENSOCUP00000003129; ENSOCUG00000003610.
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 OrthoDB; 405736at2759; -.
DR TreeFam; TF105285; -.
DR BRENDA; 1.14.13.148; 1749.
DR Proteomes; UP000001811; Chromosome 13.
DR Bgee; ENSOCUG00000003610; Expressed in liver and 12 other tissues.
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: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 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="Dimethylaniline monooxygenase [N-oxide-forming] 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
