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 08-NOV-2023, entry version 138.
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:0000269|PubMed:3739217, ECO:0000269|PubMed:7736906};
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=Hepatic flavin-containing monooxygenase 3;
DE Short=FMO 3;
DE AltName: Full=Trimethylamine monooxygenase;
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 (PubMed:3739217, PubMed:7736906).
CC Plays an important role in the metabolism of trimethylamine (TMA), via
CC the production of trimethylamine N-oxide (TMAO) metabolite. TMA is
CC generated by the action of gut microbiota using dietary precursors such
CC as choline, choline containing compounds, betaine or L-carnitine. By
CC regulating TMAO concentration, FMO3 directly impacts both platelet
CC responsiveness and rate of thrombus formation.
CC {ECO:0000250|UniProtKB:P31513, ECO:0000269|PubMed:3739217,
CC ECO:0000269|PubMed:7736906}.
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 PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:31980;
CC Evidence={ECO:0000250|UniProtKB:P31513};
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 PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:24469;
CC Evidence={ECO:0000250|UniProtKB:P31513};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=H(+) + hypotaurine + NADPH + O2 = H2O + NADP(+) + taurine;
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 = 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 PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:58721;
CC Evidence={ECO:0000250|UniProtKB:P31513};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=albendazole + H(+) + NADPH + O2 = albendazole S-oxide + H2O +
CC NADP(+); Xref=Rhea:RHEA:10796, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378,
CC ChEBI:CHEBI:15379, ChEBI:CHEBI:16664, ChEBI:CHEBI:16959,
CC ChEBI:CHEBI:57783, ChEBI:CHEBI:58349; EC=1.14.13.32;
CC Evidence={ECO:0000269|PubMed:3739217, ECO:0000269|PubMed:7736906};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:10797;
CC Evidence={ECO:0000305|PubMed:3739217};
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; 10116-ENSRNOP00000004864; -.
DR GeneID; 84493; -.
DR KEGG; rno:84493; -.
DR UCSC; RGD:619761; rat.
DR AGR; RGD:619761; -.
DR CTD; 2328; -.
DR RGD; 619761; Fmo3.
DR eggNOG; KOG1399; Eukaryota.
DR InParanoid; Q9EQ76; -.
DR OrthoDB; 2079054at2759; -.
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:0047638; F:albendazole monooxygenase activity; IEA:RHEA.
DR GO; GO:0016597; F:amino acid binding; IPI:RGD.
DR GO; GO:0050660; F:flavin adenine dinucleotide binding; IEA:InterPro.
DR GO; GO:0047822; F:hypotaurine dehydrogenase activity; ISO:RGD.
DR GO; GO:0004497; F:monooxygenase activity; TAS:RGD.
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:0042412; P:taurine biosynthetic process; ISO:RGD.
DR GO; GO:0006805; P:xenobiotic metabolic process; IDA:RGD.
DR Gene3D; 3.50.50.60; FAD/NAD(P)-binding domain; 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 PANTHER; PTHR23023; DIMETHYLANILINE MONOOXYGENASE; 1.
DR PANTHER; PTHR23023:SF44; DIMETHYLANILINE MONOOXYGENASE [N-OXIDE-FORMING] 3; 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.
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="Flavin-containing monooxygenase 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
//
