FMO3_RAT
ID FMO3_RAT Reviewed; 531 AA.
AC Q9EQ76; Q5PQV6;
DT 25-OCT-2005, integrated into UniProtKB/Swiss-Prot.
DT 01-MAR-2001, sequence version 1.
DT 03-AUG-2022, entry version 132.
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 Rattus norvegicus (Rat).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Rattus.
OX NCBI_TaxID=10116;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA], CHARACTERIZATION, AND TISSUE SPECIFICITY.
RC STRAIN=Sprague-Dawley;
RX PubMed=11414682; DOI=10.1006/abbi.2001.2317;
RA Lattard V., Buronfosse T., Lachuer J., Longin-Sauvageon C., Moulin C.,
RA Benoit E.;
RT "Cloning, sequencing, tissue distribution, and heterologous expression of
RT rat flavin-containing monooxygenase 3.";
RL Arch. Biochem. Biophys. 391:30-40(2001).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Kidney;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [3]
RP FUNCTION, AND CATALYTIC ACTIVITY.
RX PubMed=3739217; DOI=10.1007/bf02213995;
RA Fargetton X., Galtier P., Delatour P.;
RT "Sulfoxidation of albendazole by a cytochrome P450-independent
RT monooxygenase from rat liver microsomes.";
RL Vet. Res. Commun. 10:317-324(1986).
RN [4]
RP FUNCTION, AND CATALYTIC ACTIVITY.
RX PubMed=7736906;
RA Moroni P., Buronfosse T., Longin-Sauvageon C., Delatour P., Benoit E.;
RT "Chiral sulfoxidation of albendazole by the flavin adenine dinucleotide-
RT containing and cytochrome P450-dependent monooxygenases from rat liver
RT microsomes.";
RL Drug Metab. Dispos. 23:160-165(1995).
RN [5]
RP SUBCELLULAR LOCATION, AND TISSUE SPECIFICITY.
RX PubMed=19307449; DOI=10.1124/jpet.109.152058;
RA Novick R.M., Mitzey A.M., Brownfield M.S., Elfarra A.A.;
RT "Differential localization of flavin-containing monooxygenase (FMO)
RT isoforms 1, 3, and 4 in rat liver and kidney and evidence for expression of
RT FMO4 in mouse, rat, and human liver and kidney microsomes.";
RL J. Pharmacol. Exp. Ther. 329:1148-1155(2009).
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:0000269|PubMed:3739217, ECO:0000269|PubMed:7736906}.
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:0000269|PubMed:3739217, ECO:0000269|PubMed:7736906};
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 {ECO:0000269|PubMed:19307449};
CC Single-pass membrane protein {ECO:0000255}. Endoplasmic reticulum
CC membrane {ECO:0000250|UniProtKB:P32417}; Single-pass membrane protein
CC {ECO:0000255}.
CC -!- TISSUE SPECIFICITY: Detected in liver and kidney (at protein level)
CC (PubMed:19307449). Expressed in kidney and liver. Weakly expressed in
CC lung. Does not seem to be expressed in brain, adipose tissue, or
CC muscle. {ECO:0000269|PubMed:11414682, ECO:0000269|PubMed:19307449}.
CC -!- SIMILARITY: Belongs to the FMO family. {ECO:0000305}.
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DR EMBL; AF286595; AAG44891.1; -; mRNA.
DR EMBL; BC087008; AAH87008.1; -; mRNA.
DR RefSeq; NP_445885.2; NM_053433.2.
DR AlphaFoldDB; Q9EQ76; -.
DR SMR; Q9EQ76; -.
DR IntAct; Q9EQ76; 1.
DR STRING; 10116.ENSRNOP00000004864; -.
DR CarbonylDB; Q9EQ76; -.
DR iPTMnet; Q9EQ76; -.
DR PhosphoSitePlus; Q9EQ76; -.
DR PaxDb; Q9EQ76; -.
DR PRIDE; Q9EQ76; -.
DR GeneID; 84493; -.
DR KEGG; rno:84493; -.
DR UCSC; RGD:619761; rat.
DR CTD; 2328; -.
DR RGD; 619761; Fmo3.
DR eggNOG; KOG1399; Eukaryota.
DR InParanoid; Q9EQ76; -.
DR OrthoDB; 405736at2759; -.
DR PhylomeDB; Q9EQ76; -.
DR TreeFam; TF105285; -.
DR BRENDA; 1.14.13.8; 5301.
DR Reactome; R-RNO-217271; FMO oxidises nucleophiles.
DR SABIO-RK; Q9EQ76; -.
DR PRO; PR:Q9EQ76; -.
DR Proteomes; UP000002494; Unplaced.
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:0043231; C:intracellular membrane-bounded organelle; IDA:RGD.
DR GO; GO:0016597; F:amino acid binding; IPI:RGD.
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; IDA:RGD.
DR GO; GO:0050661; F:NADP binding; IPI:RGD.
DR GO; GO:0034899; F:trimethylamine monooxygenase activity; IEA:UniProtKB-EC.
DR GO; GO:0006805; P:xenobiotic metabolic process; IDA:RGD.
DR Gene3D; 3.50.50.60; -; 3.
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 Endoplasmic reticulum; FAD; Flavoprotein; Membrane; Microsome;
KW Monooxygenase; NADP; Oxidoreductase; Phosphoprotein; Reference proteome;
KW Transmembrane; Transmembrane helix.
FT CHAIN 1..531
FT /note="Dimethylaniline monooxygenase [N-oxide-forming] 3"
FT /id="PRO_0000147659"
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 MOD_RES 401
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P97501"
FT CONFLICT 501
FT /note="V -> D (in Ref. 2; AAH87008)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 531 AA; 59960 MW; 35A89988323B311F CRC64;
MKRKVAVIGA GVSGLAAIRS CLEEGLEPTC FERSDDVGGL WKFSDHTEEG RASIYQSVFT
NSSKEMMCFP DFPYPDDFPN FMHNSKLQEY ITSFATEKNL LKYIQFETLV TRINKCPDFS
TTGKWEVTTE KNSKKETAVF DAVMICSGHH VYPHLPKDSF PGLNRFKGKC FHSRDYKEPG
TWKGKRVLVI GLGNSGCDIA AELSHVAQQV IISSRSGSWV MSRVWNDGYP WDMVVITRFQ
TFLKNNLPTA ISDWWYMKQM NARFKHENYG LMPLNGTLRK EPVFNDELPA RILCGTVSIK
PNVKEFTETS AVFEDGTVFE GIDCVIFATG YGYAYPFLDD SIIKSRNNEV TLYKGIFPPQ
LEKPTMAVIG LVQSLGAAIP TTDLQARWAA QVIRGTCILP SVNDMMDDID EKMGKKLKWF
GNSTTIQTDY IVYMDELASF IGAKPNILWL FLKDPRLAIE VFFGPCSPYQ FRLVGPGKWS
GARNAILTQW DRSLKPMKTR VVGGIQKPCL YSHFLRLLAV PVLIALFLVL I
