ID FMO1_PIG Reviewed; 532 AA. AC P16549; DT 01-AUG-1990, integrated into UniProtKB/Swiss-Prot. DT 23-JAN-2007, sequence version 3. DT 13-SEP-2023, entry version 163. DE RecName: Full=Flavin-containing monooxygenase 1 {ECO:0000305|PubMed:7758472}; DE EC=1.14.13.148 {ECO:0000250|UniProtKB:P36365}; DE EC=1.14.13.8 {ECO:0000269|PubMed:7758472}; DE AltName: Full=Dimethylaniline monooxygenase [N-oxide-forming] 1; DE AltName: Full=Dimethylaniline oxidase 1; DE AltName: Full=Hepatic flavin-containing monooxygenase 1; DE Short=FMO 1; DE AltName: Full=Trimethylamine monooxygenase {ECO:0000305}; GN Name=FMO1; Synonyms=FMO-1; OS Sus scrofa (Pig). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; OC Eutheria; Laurasiatheria; Artiodactyla; Suina; Suidae; Sus. OX NCBI_TaxID=9823; RN [1] RP NUCLEOTIDE SEQUENCE [MRNA], PROTEIN SEQUENCE OF 137-151 AND 309-318, AND RP TISSUE SPECIFICITY. RC TISSUE=Liver; RX PubMed=2322534; DOI=10.1021/bi00453a014; RA Gasser R., Tynes R.E., Lawton M.P., Korsmeyer K.K., Ziegler D.M., RA Philpot R.M.; RT "The flavin-containing monooxygenase expressed in pig liver: primary RT sequence, distribution, and evidence for a single gene."; RL Biochemistry 29:119-124(1990). RN [2] RP PROTEIN SEQUENCE OF 2-14 AND 185-202, ACETYLATION AT ALA-2, AND RP IDENTIFICATION BY MASS SPECTROMETRY. RC TISSUE=Liver; RX PubMed=2383273; DOI=10.1016/0006-291x(90)92181-x; RA Guan S.H., Falick A.M., Cashman J.R.; RT "N-terminus determination: FAD and NADP binding domain mapping of hog liver RT flavin-containing monooxygenase by tandem mass spectrometry."; RL Biochem. Biophys. Res. Commun. 170:937-943(1990). RN [3] RP PROTEIN SEQUENCE OF 186-208, FUNCTION, CATALYTIC ACTIVITY, SUBCELLULAR RP LOCATION, AND SITE. RC TISSUE=Liver; RX PubMed=7758472; DOI=10.1111/j.1432-1033.1995.tb20523.x; RA Wu R.-F., Ichikawa Y.; RT "An essential lysyl residue (Lys208) in the substrate-binding site of RT porcine FAD-containing monooxygenase."; RL Eur. J. Biochem. 229:749-753(1995). RN [4] RP GLYCOSYLATION AT ASN-120, AND TOPOLOGY. RX PubMed=9778310; DOI=10.1021/tx980117p; RA Korsmeyer K.K., Guan S., Yang Z.C., Falick A.M., Ziegler D.M., RA Cashman J.R.; RT "N-glycosylation of pig flavin-containing monooxygenase form 1: RT determination of the site of protein modification by mass spectrometry."; RL Chem. Res. Toxicol. 11:1145-1153(1998). CC -!- FUNCTION: Broad spectrum monooxygenase that catalyzes the oxygenation CC of a wide variety of nitrogen- and sulfur-containing compounds CC including xenobiotics (PubMed:7758472). Catalyzes the S-oxygenation of CC hypotaurine to produce taurine, an organic osmolyte involved in cell CC volume regulation as well as a variety of cytoprotective and CC developmental processes (By similarity). In vitro, catalyzes the N- CC oxygenation of trimethylamine (TMA) to produce trimethylamine N-oxide CC (TMAO) and could therefore participate to the detoxification of this CC compound that is generated by the action of gut microbiota from dietary CC precursors such as choline, choline containing compounds, betaine or L- CC carnitine (By similarity). {ECO:0000250|UniProtKB:P36365, CC ECO:0000250|UniProtKB:Q01740, ECO:0000269|PubMed:7758472}. 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:Q01740}; CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:69820; CC Evidence={ECO:0000250|UniProtKB:Q01740}; CC -!- CATALYTIC ACTIVITY: CC Reaction=H(+) + hypotaurine + NADH + O2 = H2O + NAD(+) + taurine; CC Xref=Rhea:RHEA:74111, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, CC ChEBI:CHEBI:15379, ChEBI:CHEBI:57540, ChEBI:CHEBI:57853, CC ChEBI:CHEBI:57945, ChEBI:CHEBI:507393; EC=1.14.13.8; CC Evidence={ECO:0000250|UniProtKB:Q01740}; CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:74112; CC Evidence={ECO:0000250|UniProtKB:Q01740}; 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:P36365}; CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:31980; CC Evidence={ECO:0000250|UniProtKB:P36365}; 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:0000269|PubMed:7758472}; CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:24469; CC Evidence={ECO:0000305|PubMed:7758472}; CC -!- COFACTOR: CC Name=FAD; Xref=ChEBI:CHEBI:57692; CC Evidence={ECO:0000250|UniProtKB:Q01740}; CC -!- SUBCELLULAR LOCATION: Endoplasmic reticulum membrane CC {ECO:0000269|PubMed:7758472}; Single-pass membrane protein CC {ECO:0000255}. CC -!- TISSUE SPECIFICITY: Liver. {ECO:0000269|PubMed:2322534}. CC -!- SIMILARITY: Belongs to the FMO family. {ECO:0000305}. CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- DR EMBL; M32031; AAA31033.1; -; mRNA. DR PIR; A33768; A33768. DR RefSeq; NP_999229.1; NM_214064.1. DR RefSeq; XP_005656702.1; XM_005656645.2. DR AlphaFoldDB; P16549; -. DR SMR; P16549; -. DR STRING; 9823.ENSSSCP00000016191; -. DR GlyCosmos; P16549; 1 site, No reported glycans. DR iPTMnet; P16549; -. DR PaxDb; P16549; -. DR PeptideAtlas; P16549; -. DR Ensembl; ENSSSCT00005029955; ENSSSCP00005018242; ENSSSCG00005018850. DR Ensembl; ENSSSCT00005029982; ENSSSCP00005018261; ENSSSCG00005018850. DR Ensembl; ENSSSCT00005030014; ENSSSCP00005018283; ENSSSCG00005018850. DR Ensembl; ENSSSCT00005030021; ENSSSCP00005018288; ENSSSCG00005018850. DR Ensembl; ENSSSCT00035075473; ENSSSCP00035030726; ENSSSCG00035056479. DR Ensembl; ENSSSCT00045057157; ENSSSCP00045039947; ENSSSCG00045033391. DR Ensembl; ENSSSCT00050083786; ENSSSCP00050035963; ENSSSCG00050061478. DR Ensembl; ENSSSCT00055024748; ENSSSCP00055019643; ENSSSCG00055012560. DR Ensembl; ENSSSCT00065045563; ENSSSCP00065019538; ENSSSCG00065033525. DR Ensembl; ENSSSCT00065045579; ENSSSCP00065019546; ENSSSCG00065033525. DR Ensembl; ENSSSCT00065045588; ENSSSCP00065019551; ENSSSCG00065033525. DR Ensembl; ENSSSCT00070043455; ENSSSCP00070036573; ENSSSCG00070021841. DR Ensembl; ENSSSCT00070043463; ENSSSCP00070036581; ENSSSCG00070021841. DR Ensembl; ENSSSCT00070043480; ENSSSCP00070036597; ENSSSCG00070021841. DR GeneID; 397132; -. DR KEGG; ssc:397132; -. DR CTD; 2326; -. DR eggNOG; KOG1399; Eukaryota. DR HOGENOM; CLU_006909_8_2_1; -. DR InParanoid; P16549; -. DR OMA; VMIKEVN; -. DR OrthoDB; 2079054at2759; -. DR TreeFam; TF105285; -. DR Reactome; R-SSC-1614558; Degradation of cysteine and homocysteine. DR Reactome; R-SSC-217271; FMO oxidises nucleophiles. DR SABIO-RK; P16549; -. DR Proteomes; UP000008227; Chromosome 9. DR Proteomes; UP000314985; Chromosome 9. DR Proteomes; UP000694570; Unplaced. DR Proteomes; UP000694571; Unplaced. DR Proteomes; UP000694720; Unplaced. DR Proteomes; UP000694722; Unplaced. DR Proteomes; UP000694723; Unplaced. DR Proteomes; UP000694724; Unplaced. DR Proteomes; UP000694725; Unplaced. DR Proteomes; UP000694726; Unplaced. DR Proteomes; UP000694727; Unplaced. DR Proteomes; UP000694728; Unplaced. DR Bgee; ENSSSCG00000015268; Expressed in lung and 43 other tissues. DR ExpressionAtlas; P16549; baseline and differential. DR Genevisible; P16549; SS. DR GO; GO:0005789; C:endoplasmic reticulum membrane; IDA:UniProtKB. DR GO; GO:0050660; F:flavin adenine dinucleotide binding; IEA:InterPro. DR GO; GO:0047822; F:hypotaurine dehydrogenase activity; ISS:UniProtKB. DR GO; GO:0004499; F:N,N-dimethylaniline monooxygenase activity; IDA:UniProtKB. DR GO; GO:0050661; F:NADP binding; IEA:InterPro. DR GO; GO:0034899; F:trimethylamine monooxygenase activity; ISS:UniProtKB. DR GO; GO:0070995; P:NADPH oxidation; IDA:BHF-UCL. DR GO; GO:0006082; P:organic acid metabolic process; IDA:BHF-UCL. DR GO; GO:0042412; P:taurine biosynthetic process; ISS:UniProtKB. DR GO; GO:0009404; P:toxin metabolic process; IDA:BHF-UCL. DR Gene3D; 3.50.50.60; FAD/NAD(P)-binding domain; 4. DR InterPro; IPR036188; FAD/NAD-bd_sf. DR InterPro; IPR000960; Flavin_mOase. DR InterPro; IPR020946; Flavin_mOase-like. DR InterPro; IPR002253; Flavin_mOase_1. DR PANTHER; PTHR23023; DIMETHYLANILINE MONOOXYGENASE; 1. DR PANTHER; PTHR23023:SF154; DIMETHYLANILINE MONOOXYGENASE [N-OXIDE-FORMING] 1; 1. DR Pfam; PF00743; FMO-like; 1. DR PIRSF; PIRSF000332; FMO; 1. DR PRINTS; PR00370; FMOXYGENASE. DR PRINTS; PR01121; FMOXYGENASE1. DR SUPFAM; SSF51905; FAD/NAD(P)-binding domain; 3. PE 1: Evidence at protein level; KW Acetylation; Direct protein sequencing; Endoplasmic reticulum; FAD; KW Flavoprotein; Glycoprotein; Membrane; Monooxygenase; NADP; Oxidoreductase; KW Reference proteome; Transmembrane; Transmembrane helix. FT INIT_MET 1 FT /note="Removed" FT /evidence="ECO:0000269|PubMed:2383273" FT CHAIN 2..532 FT /note="Flavin-containing monooxygenase 1" FT /id="PRO_0000147641" FT TOPO_DOM 2..510 FT /note="Lumenal" FT /evidence="ECO:0000305|PubMed:9778310" FT TRANSMEM 511..531 FT /note="Helical" FT /evidence="ECO:0000255" FT TOPO_DOM 532 FT /note="Cytoplasmic" FT /evidence="ECO:0000305|PubMed:9778310" 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 SITE 208 FT /note="Important for substrate binding" FT /evidence="ECO:0000269|PubMed:7758472" FT MOD_RES 2 FT /note="N-acetylalanine" FT /evidence="ECO:0000269|PubMed:2383273" FT CARBOHYD 120 FT /note="N-linked (GlcNAc...) (high mannose) asparagine" FT /evidence="ECO:0000269|PubMed:9778310" SQ SEQUENCE 532 AA; 59952 MW; 5E475E7F2F3B8A67 CRC64; MAKRVAIVGA GVSGLASIKC CLEEGLEPTC FERSDDLGGL WRFTEHVEEG RASLYKSVVS NSCKEMSCYP DFPFPEDYPN YVPNSHFLEY LRMYANQFNL LKCIQFKTKV CSVTKHEDFN TTGQWDVVTL CEGKQESAVF DAVMVCTGFL TNPYLPLDSF PGINTFKGQY FHSRQYKHPD IFKDKSVLVV GMGNSGTDIA VEASHLAKKV FLSTTGGAWV ISRVFDSGYP WDMVFMTRFQ NMFRNSLPTP IVNWLIAKKM NSWFNHANYG LIPEDRIQLR EPVLNDELPG RIITGKVLIK PSIKEVKENS VVFNSSPEEE PIDIIVFATG YTFAFPFLDE SVVKVEDGQA SLYKYIFPAH LQKPTLAVIG LIKPLGSLLP TGDTQARWAV RVLKGVNKLP PSSVMIQEVN TRKENKPSGF GLCYCKALQS DYIAYIDELL TYIDAKPNMF SLLLTDPHLA LTIFFGPCTP YQFRLTGPGK WEGARNAIMT QWDRTFKVTK TRIVKESPSP FASLLKLFSF LALLVAIFQI FL //