ID   FMO3_MOUSE              Reviewed;         534 AA.
AC   P97501;
DT   01-NOV-1997, integrated into UniProtKB/Swiss-Prot.
DT   01-MAY-1997, sequence version 1.
DT   27-MAR-2024, entry version 182.
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=Hepatic flavin-containing monooxygenase 3;
DE            Short=FMO 3;
DE   AltName: Full=Trimethylamine monooxygenase;
GN   Name=Fmo3;
OS   Mus musculus (Mouse).
OC   Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC   Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC   Murinae; Mus; Mus.
OX   NCBI_TaxID=10090;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [MRNA].
RC   STRAIN=CD-1; TISSUE=Liver;
RX   PubMed=9344459; DOI=10.1006/abbi.1997.0322;
RA   Falls J.G., Cherrington N.J., Clements K.M., Philpot R.M., Levi P.E.,
RA   Rose R.L., Hodgson E.;
RT   "Molecular cloning, sequencing, and expression in Escherichia coli of mouse
RT   flavin-containing monooxygenase 3 (FMO3): comparison with the human
RT   isoform.";
RL   Arch. Biochem. Biophys. 347:9-18(1997).
RN   [2]
RP   PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-401, AND IDENTIFICATION BY
RP   MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC   TISSUE=Embryonic fibroblast;
RX   PubMed=19131326; DOI=10.1074/mcp.m800451-mcp200;
RA   Sweet S.M., Bailey C.M., Cunningham D.L., Heath J.K., Cooper H.J.;
RT   "Large scale localization of protein phosphorylation by use of electron
RT   capture dissociation mass spectrometry.";
RL   Mol. Cell. Proteomics 8:904-912(2009).
RN   [3]
RP   IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC   TISSUE=Liver, and Lung;
RX   PubMed=21183079; DOI=10.1016/j.cell.2010.12.001;
RA   Huttlin E.L., Jedrychowski M.P., Elias J.E., Goswami T., Rad R.,
RA   Beausoleil S.A., Villen J., Haas W., Sowa M.E., Gygi S.P.;
RT   "A tissue-specific atlas of mouse protein phosphorylation and expression.";
RL   Cell 143:1174-1189(2010).
RN   [4]
RP   FUNCTION, AND INDUCTION.
RX   PubMed=23177478; DOI=10.1016/j.cub.2012.10.047;
RA   Li Q., Korzan W.J., Ferrero D.M., Chang R.B., Roy D.S., Buchi M.,
RA   Lemon J.K., Kaur A.W., Stowers L., Fendt M., Liberles S.D.;
RT   "Synchronous evolution of an odor biosynthesis pathway and behavioral
RT   response.";
RL   Curr. Biol. 23:11-20(2013).
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:23177478}.
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: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; 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   -!- TISSUE SPECIFICITY: Liver.
CC   -!- INDUCTION: Expression is specifically repressed in male mice after
CC       puberty, preventing trimethylamine degradation. Trimethylamine is
CC       present at high concentration in the urine of male mice after puberty
CC       and acts as an attractant. {ECO:0000269|PubMed:23177478}.
CC   -!- MISCELLANEOUS: Trimethylamine is a bacterial metabolite found in some
CC       animal odors, and is a repulsive odor associated with bad breath and
CC       spoiled food for most organisms, except for M.musculus, where it acts
CC       as an attractant. {ECO:0000305|PubMed:23177478}.
CC   -!- SIMILARITY: Belongs to the FMO family. {ECO:0000305}.
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DR   EMBL; U87147; AAB47541.1; -; mRNA.
DR   CCDS; CCDS15426.1; -.
DR   RefSeq; NP_032056.1; NM_008030.2.
DR   AlphaFoldDB; P97501; -.
DR   SMR; P97501; -.
DR   BioGRID; 199713; 3.
DR   STRING; 10090.ENSMUSP00000028010; -.
DR   iPTMnet; P97501; -.
DR   PhosphoSitePlus; P97501; -.
DR   SwissPalm; P97501; -.
DR   jPOST; P97501; -.
DR   PaxDb; 10090-ENSMUSP00000028010; -.
DR   PeptideAtlas; P97501; -.
DR   ProteomicsDB; 273010; -.
DR   Antibodypedia; 2219; 399 antibodies from 32 providers.
DR   DNASU; 14262; -.
DR   Ensembl; ENSMUST00000028010.9; ENSMUSP00000028010.8; ENSMUSG00000026691.11.
DR   GeneID; 14262; -.
DR   KEGG; mmu:14262; -.
DR   UCSC; uc007dhe.1; mouse.
DR   AGR; MGI:1100496; -.
DR   CTD; 2328; -.
DR   MGI; MGI:1100496; Fmo3.
DR   VEuPathDB; HostDB:ENSMUSG00000026691; -.
DR   eggNOG; KOG1399; Eukaryota.
DR   GeneTree; ENSGT00940000161339; -.
DR   HOGENOM; CLU_006909_8_2_1; -.
DR   InParanoid; P97501; -.
DR   OMA; DCYERET; -.
DR   OrthoDB; 2079054at2759; -.
DR   PhylomeDB; P97501; -.
DR   TreeFam; TF105285; -.
DR   BRENDA; 1.14.13.148; 3474.
DR   BRENDA; 1.14.13.8; 3474.
DR   Reactome; R-MMU-217271; FMO oxidises nucleophiles.
DR   BioGRID-ORCS; 14262; 1 hit in 62 CRISPR screens.
DR   PRO; PR:P97501; -.
DR   Proteomes; UP000000589; Chromosome 1.
DR   RNAct; P97501; Protein.
DR   Bgee; ENSMUSG00000026691; Expressed in right lung lobe and 56 other cell types or tissues.
DR   ExpressionAtlas; P97501; baseline and differential.
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; ISO:MGI.
DR   GO; GO:0050660; F:flavin adenine dinucleotide binding; IEA:InterPro.
DR   GO; GO:0047822; F:hypotaurine dehydrogenase activity; ISO:MGI.
DR   GO; GO:0004499; F:N,N-dimethylaniline monooxygenase activity; ISO:MGI.
DR   GO; GO:0050661; F:NADP binding; ISO:MGI.
DR   GO; GO:0034899; F:trimethylamine monooxygenase activity; IEA:UniProtKB-EC.
DR   GO; GO:0042412; P:taurine biosynthetic process; ISO:MGI.
DR   GO; GO:0006805; P:xenobiotic metabolic process; ISO:MGI.
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   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.
DR   Genevisible; P97501; MM.
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..534
FT                   /note="Flavin-containing monooxygenase 3"
FT                   /id="PRO_0000147656"
FT   TRANSMEM        514..534
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:0007744|PubMed:19131326"
SQ   SEQUENCE   534 AA;  60516 MW;  F72F7993C01AF9C9 CRC64;
     MKKKVAIIGA GVSGLAAIRS CLEEGLEPTC FERSDDVGGL WKFSDHIEEG RASIYQSVFT
     NSSKEMMCFP DFPYPDDFPN FMHHSKLQEY ITSFAKEKNL LKYIQFETPV TSINKCPNFS
     TTGKWEVTTE KHGKKETAVF DATMICSGHH IFPHVPKDSF PGLNRFKGKC FHSRDYKEPG
     IWKGKRVLVI GLGNSGCDIA AELSHVAQKV TISSRSGSWV MSRVWDDGYP WDMVVLTRFQ
     TFLKNNLPTA ISDWWYTRQM NARFKHENYG LVPLNRTLRK EPVFNDELPA RILCGMVTIK
     PNVKEFTETS AVFEDGTMFE AIDCVIFATG YGYAYPFLDD SIIKSRNNEV TLYKGVFPPQ
     LEKPTMAVIG LVQSLGATIP ITDLQARWAA QVIKGTCTLP SVNDMMDDID EKMGEKFKWY
     GNSTTIQTDY IVYMDELASF IGAKPNLLWL FLKDPRLAVE VFFGPCSPYQ FRLVGPGKWS
     GARNAILTQW DRSLKPMKTR VVSKVQKSCS HFYSRLLRLL AVPVLLIALF LVLI
//