FMO3_MOUSE
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 03-AUG-2022, entry version 173.
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 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=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; 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; P97501; -.
DR PeptideAtlas; P97501; -.
DR PRIDE; P97501; -.
DR ProteomicsDB; 273010; -.
DR Antibodypedia; 2219; 367 antibodies from 32 providers.
DR DNASU; 14262; -.
DR Ensembl; ENSMUST00000028010; ENSMUSP00000028010; ENSMUSG00000026691.
DR GeneID; 14262; -.
DR KEGG; mmu:14262; -.
DR UCSC; uc007dhe.1; mouse.
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; SIPWLFL; -.
DR OrthoDB; 405736at2759; -.
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 59 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 tissues.
DR ExpressionAtlas; P97501; baseline and differential.
DR Genevisible; P97501; MM.
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; ISO:MGI.
DR GO; GO:0016597; F:amino acid binding; ISO:MGI.
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; 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:0006805; P:xenobiotic metabolic process; ISO:MGI.
DR Gene3D; 3.50.50.60; -; 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 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..534
FT /note="Dimethylaniline monooxygenase [N-oxide-forming] 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
