ID FMO3_HUMAN Reviewed; 532 AA. AC P31513; B2R816; Q14854; Q8N5N5; DT 01-JUL-1993, integrated into UniProtKB/Swiss-Prot. DT 23-JAN-2007, sequence version 5. DT 11-NOV-2015, entry version 162. DE RecName: Full=Dimethylaniline monooxygenase [N-oxide-forming] 3; DE EC=1.14.13.8; DE AltName: Full=Dimethylaniline oxidase 3; DE AltName: Full=FMO II; DE AltName: Full=FMO form 2; 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 Homo sapiens (Human). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; OC Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; OC Catarrhini; Hominidae; Homo. OX NCBI_TaxID=9606; RN [1] RP NUCLEOTIDE SEQUENCE [MRNA]. RC TISSUE=Liver; RX PubMed=1542660; DOI=10.1073/pnas.89.5.1685; RA Lomri N., Gu Q., Cashman J.R.; RT "Molecular cloning of the flavin-containing monooxygenase (form II) RT cDNA from adult human liver."; RL Proc. Natl. Acad. Sci. U.S.A. 89:1685-1689(1992). RN [2] RP NUCLEOTIDE SEQUENCE [MRNA]. RC TISSUE=Liver; RX PubMed=8654418; DOI=10.1111/j.1432-1033.1996.00683.x; RA Dolphin C.T., Cullingford T.E., Shephard E.A., Smith R.L., RA Phillips I.R.; RT "Differential developmental and tissue-specific regulation of RT expression of the genes encoding three members of the flavin- RT containing monooxygenase family of man, FMO1, FMO3 and FM04."; RL Eur. J. Biochem. 235:683-689(1996). RN [3] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA]. RX PubMed=9417913; DOI=10.1006/geno.1997.5031; RA Dolphin C.T., Riley J.H., Smith R.L., Shephard E.A., Phillips I.R.; RT "Structural organization of the human flavin-containing monooxygenase RT 3 gene (FMO3), the favored candidate for fish-odor syndrome, RT determined directly from genomic DNA."; RL Genomics 46:260-267(1997). RN [4] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND VARIANTS HIS-132; LYS-158; RP CYS-205; MET-257; ALA-277; GLY-308; PRO-360 AND GLN-362. RG NIEHS SNPs program; RL Submitted (JAN-2005) to the EMBL/GenBank/DDBJ databases. RN [5] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. RC TISSUE=Liver; RX PubMed=14702039; DOI=10.1038/ng1285; RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S., RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., RA Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., RA Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., RA Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M., RA Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K., RA Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S., RA Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J., RA Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y., RA Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N., RA Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S., RA Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., RA Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T., RA Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y., RA Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S., RA Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T., RA Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M., RA Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T., RA Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K., RA Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R., RA Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S.; RT "Complete sequencing and characterization of 21,243 full-length human RT cDNAs."; RL Nat. Genet. 36:40-45(2004). RN [6] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RX PubMed=16710414; DOI=10.1038/nature04727; RA Gregory S.G., Barlow K.F., McLay K.E., Kaul R., Swarbreck D., RA Dunham A., Scott C.E., Howe K.L., Woodfine K., Spencer C.C.A., RA Jones M.C., Gillson C., Searle S., Zhou Y., Kokocinski F., RA McDonald L., Evans R., Phillips K., Atkinson A., Cooper R., Jones C., RA Hall R.E., Andrews T.D., Lloyd C., Ainscough R., Almeida J.P., RA Ambrose K.D., Anderson F., Andrew R.W., Ashwell R.I.S., Aubin K., RA Babbage A.K., Bagguley C.L., Bailey J., Beasley H., Bethel G., RA Bird C.P., Bray-Allen S., Brown J.Y., Brown A.J., Buckley D., RA Burton J., Bye J., Carder C., Chapman J.C., Clark S.Y., Clarke G., RA Clee C., Cobley V., Collier R.E., Corby N., Coville G.J., Davies J., RA Deadman R., Dunn M., Earthrowl M., Ellington A.G., Errington H., RA Frankish A., Frankland J., French L., Garner P., Garnett J., Gay L., RA Ghori M.R.J., Gibson R., Gilby L.M., Gillett W., Glithero R.J., RA Grafham D.V., Griffiths C., Griffiths-Jones S., Grocock R., RA Hammond S., Harrison E.S.I., Hart E., Haugen E., Heath P.D., RA Holmes S., Holt K., Howden P.J., Hunt A.R., Hunt S.E., Hunter G., RA Isherwood J., James R., Johnson C., Johnson D., Joy A., Kay M., RA Kershaw J.K., Kibukawa M., Kimberley A.M., King A., Knights A.J., RA Lad H., Laird G., Lawlor S., Leongamornlert D.A., Lloyd D.M., RA Loveland J., Lovell J., Lush M.J., Lyne R., Martin S., RA Mashreghi-Mohammadi M., Matthews L., Matthews N.S.W., McLaren S., RA Milne S., Mistry S., Moore M.J.F., Nickerson T., O'Dell C.N., RA Oliver K., Palmeiri A., Palmer S.A., Parker A., Patel D., Pearce A.V., RA Peck A.I., Pelan S., Phelps K., Phillimore B.J., Plumb R., Rajan J., RA Raymond C., Rouse G., Saenphimmachak C., Sehra H.K., Sheridan E., RA Shownkeen R., Sims S., Skuce C.D., Smith M., Steward C., RA Subramanian S., Sycamore N., Tracey A., Tromans A., Van Helmond Z., RA Wall M., Wallis J.M., White S., Whitehead S.L., Wilkinson J.E., RA Willey D.L., Williams H., Wilming L., Wray P.W., Wu Z., Coulson A., RA Vaudin M., Sulston J.E., Durbin R.M., Hubbard T., Wooster R., RA Dunham I., Carter N.P., McVean G., Ross M.T., Harrow J., Olson M.V., RA Beck S., Rogers J., Bentley D.R.; RT "The DNA sequence and biological annotation of human chromosome 1."; RL Nature 441:315-321(2006). RN [7] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., RA Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., RA Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., RA Hannenhalli S., Turner R., Yooseph S., Lu F., Nusskern D.R., RA Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H., RA Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G., RA Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W., RA Venter J.C.; RL Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases. RN [8] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA], AND VARIANT MET-257. RC TISSUE=Brain, and Lung; 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 RT project: the Mammalian Gene Collection (MGC)."; RL Genome Res. 14:2121-2127(2004). RN [9] RP PROTEIN SEQUENCE OF 2-10, FUNCTION, AND IDENTIFICATION BY MASS RP SPECTROMETRY. RX PubMed=9224773; RA Haining R.L., Hunter A.P., Sadeque A.J., Philpot R.M., Rettie A.E.; RT "Baculovirus-mediated expression and purification of human FMO3: RT catalytic, immunochemical, and structural characterization."; RL Drug Metab. Dispos. 25:790-797(1997). RN [10] RP CATALYTIC ACTIVITY, VARIANTS TMAU ILE-66 AND LEU-153, AND VARIANTS RP LYS-158; MET-257 AND GLY-308. RX PubMed=9536088; DOI=10.1093/hmg/7.5.839; RA Treacy E.P., Akerman B.R., Chow L.M.L., Youil R., Bibeau C., Lin J., RA Bruce A.G., Knight M., Danks D.M., Cashman J.R., Forrest S.M.; RT "Mutations of the flavin-containing monooxygenase gene (FMO3) cause RT trimethylaminuria, a defect in detoxication."; RL Hum. Mol. Genet. 7:839-845(1998). RN [11] RP BIOPHYSICOCHEMICAL PROPERTIES, CHARACTERIZATION OF VARIANTS TMAU RP SER-61; ILE-66; LEU-153 AND TRP-492, AND CHARACTERIZATION OF VARIANTS RP LYS-158; MET-257 AND GLY-308. RX PubMed=17531949; DOI=10.1016/j.abb.2007.04.014; RA Yeung C.K., Adman E.T., Rettie A.E.; RT "Functional characterization of genetic variants of human FMO3 RT associated with trimethylaminuria."; RL Arch. Biochem. Biophys. 464:251-259(2007). RN [12] RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Liver; RX PubMed=24275569; DOI=10.1016/j.jprot.2013.11.014; RA Bian Y., Song C., Cheng K., Dong M., Wang F., Huang J., Sun D., RA Wang L., Ye M., Zou H.; RT "An enzyme assisted RP-RPLC approach for in-depth analysis of human RT liver phosphoproteome."; RL J. Proteomics 96:253-262(2014). RN [13] RP VARIANTS TMAU ILE-66 AND TRP-492. RX PubMed=10338091; RX DOI=10.1002/(SICI)1098-1004(1999)13:5<376::AID-HUMU5>3.0.CO;2-A; RA Akerman B.R., Forrest S.M., Chow L.M.L., Youil R., Knight M., RA Treacy E.P.; RT "Two novel mutations of the FMO3 gene in a proband with RT trimethylaminuria."; RL Hum. Mutat. 13:376-379(1999). RN [14] RP VARIANTS TMAU THR-52 AND LEU-387, AND VARIANTS LYS-158 AND GLY-308. RX PubMed=10479479; DOI=10.1006/mgme.1999.2885; RA Akerman B.R., Lemass H., Chow L.M.L., Lambert D.M., Greenberg C., RA Bibeau C., Mamer O.A., Treacy E.P.; RT "Trimethylaminuria is caused by mutations of the FMO3 gene in a North RT American cohort."; RL Mol. Genet. Metab. 68:24-31(1999). RN [15] RP VARIANTS TMAU SER-61; LEU-153; ILE-434 AND TRP-492, AND RP CHARACTERIZATION OF VARIANTS TMAU SER-61; LEU-153; ILE-434 AND RP TRP-492. RX PubMed=11191884; DOI=10.1097/00008571-200012000-00005; RA Dolphin C.T., Janmohamed A., Smith R.L., Shephard E.A., Phillips I.R.; RT "Compound heterozygosity for missense mutations in the flavin- RT containing monooxygenase 3 (FM03) gene in patients with fish-odour RT syndrome."; RL Pharmacogenetics 10:799-807(2000). RN [16] RP VARIANTS HIS-132; LYS-158; MET-257; PRO-360; GLN-362 AND ARG-503. RX PubMed=12527699; DOI=10.1124/dmd.31.2.187; RA Furnes B., Feng J., Sommer S.S., Schlenk D.; RT "Identification of novel variants of the flavin-containing RT monooxygenase gene family in African Americans."; RL Drug Metab. Dispos. 31:187-193(2003). RN [17] RP VARIANTS GLU-198 AND CYS-205. RX PubMed=15618753; DOI=10.2133/dmpk.18.333; RA Fujieda M., Yamazaki H., Togashi M., Saito T., Kamataki T.; RT "Two novel single nucleotide polymorphisms (SNPs) of the FMO3 gene in RT Japanese."; RL Drug Metab. Pharmacokinet. 18:333-335(2003). RN [18] RP VARIANT TMAU LYS-32. RX PubMed=12893987; DOI=10.1097/00008571-200308000-00007; RA Zhang J., Tran Q., Lattard V., Cashman J.R.; RT "Deleterious mutations in the flavin-containing monooxygenase 3 (FMO3) RT gene causing trimethylaminuria."; RL Pharmacogenetics 13:495-500(2003). RN [19] RP VARIANTS ASP-24; LYS-61; LYS-158; MET-257; GLY-308 AND ASN-416, RP BIOPHYSICOCHEMICAL PROPERTIES, AND CHARACTERIZATION OF VARIANTS RP ASP-24; LYS-61 AND ASN-416. RX PubMed=17050781; DOI=10.1124/jpet.106.112268; RA Koukouritaki S.B., Poch M.T., Henderson M.C., Siddens L.K., RA Krueger S.K., VanDyke J.E., Williams D.E., Pajewski N.M., Wang T., RA Hines R.N.; RT "Identification and functional analysis of common human flavin- RT containing monooxygenase 3 genetic variants."; RL J. Pharmacol. Exp. Ther. 320:266-273(2007). CC -!- FUNCTION: Involved in the oxidative metabolism of a variety of CC xenobiotics such as drugs and pesticides. It N-oxygenates primary CC aliphatic alkylamines as well as secondary and tertiary amines. CC Plays an important role in the metabolism of trimethylamine (TMA), CC via the production of TMA N-oxide (TMAO). Is also able to perform CC S-oxidation when acting on sulfide compounds (PubMed:9224773). CC {ECO:0000250|UniProtKB:P97501, ECO:0000269|PubMed:9224773}. CC -!- CATALYTIC ACTIVITY: N,N-dimethylaniline + NADPH + O(2) = N,N- CC dimethylaniline N-oxide + NADP(+) + H(2)O. CC {ECO:0000269|PubMed:9536088}. CC -!- CATALYTIC ACTIVITY: N,N,N-trimethylamine + NADPH + O(2) = N,N,N- CC trimethylamine N-oxide + NADP(+) + H(2)O. CC {ECO:0000269|PubMed:9536088}. CC -!- COFACTOR: CC Name=FAD; Xref=ChEBI:CHEBI:57692; CC -!- BIOPHYSICOCHEMICAL PROPERTIES: CC Kinetic parameters: CC KM=21 uM for trimethylamine (at pH 8.5) CC {ECO:0000269|PubMed:17050781, ECO:0000269|PubMed:17531949}; CC KM=31 uM for trimethylamine (at pH 7.4 and 37 degrees Celsius) CC {ECO:0000269|PubMed:17050781, ECO:0000269|PubMed:17531949}; CC KM=43 uM for benzydamine (at pH 7.4 and 37 degrees Celsius) CC {ECO:0000269|PubMed:17050781, ECO:0000269|PubMed:17531949}; CC KM=55.7 uM for ethylenethiourea (at pH 8.5) CC {ECO:0000269|PubMed:17050781, ECO:0000269|PubMed:17531949}; CC KM=71.8 uM for methimazole (at pH 8.5) CC {ECO:0000269|PubMed:17050781, ECO:0000269|PubMed:17531949}; CC KM=150.1 uM for sulindac (at pH 8.5) CC {ECO:0000269|PubMed:17050781, ECO:0000269|PubMed:17531949}; CC KM=248 uM for methyl p-tolyl sulfide (at pH 7.4 and 37 degrees CC Celsius) {ECO:0000269|PubMed:17050781, CC ECO:0000269|PubMed:17531949}; CC -!- SUBCELLULAR LOCATION: Microsome membrane. Endoplasmic reticulum CC membrane. CC -!- TISSUE SPECIFICITY: Liver. CC -!- DISEASE: Trimethylaminuria (TMAU) [MIM:602079]: Inborn error of CC metabolism associated with an offensive body odor and caused by CC deficiency of FMO-mediated N-oxidation of amino-trimethylamine CC (TMA) derived from foodstuffs. Affected individuals excrete CC relatively large amounts of TMA in their urine, sweat, and breath, CC and exhibit a fishy body odor characteristic of the malodorous CC free amine. {ECO:0000269|PubMed:10338091, CC ECO:0000269|PubMed:10479479, ECO:0000269|PubMed:11191884, CC ECO:0000269|PubMed:12893987, ECO:0000269|PubMed:9536088}. Note=The CC disease is caused by mutations affecting the gene represented in CC this entry. CC -!- SIMILARITY: Belongs to the FMO family. {ECO:0000305}. CC -!- WEB RESOURCE: Name=NIEHS-SNPs; CC URL="http://egp.gs.washington.edu/data/fmo3/"; CC -!- WEB RESOURCE: Name=Protein Spotlight; Note=A case for discomfort - CC Issue 149 of June 2013; CC URL="http://web.expasy.org/spotlight/back_issues/149"; 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; M83772; AAA86284.1; -; mRNA. DR EMBL; Z47552; CAA87632.1; -; mRNA. DR EMBL; U39967; AAC51932.1; -; Genomic_DNA. DR EMBL; U39961; AAC51932.1; JOINED; Genomic_DNA. DR EMBL; U39962; AAC51932.1; JOINED; Genomic_DNA. DR EMBL; U39963; AAC51932.1; JOINED; Genomic_DNA. DR EMBL; U39964; AAC51932.1; JOINED; Genomic_DNA. DR EMBL; U39965; AAC51932.1; JOINED; Genomic_DNA. DR EMBL; U39966; AAC51932.1; JOINED; Genomic_DNA. DR EMBL; AY895830; AAW65372.1; -; Genomic_DNA. DR EMBL; AK313197; BAG36013.1; -; mRNA. DR EMBL; AL021026; CAA15908.1; -; Genomic_DNA. DR EMBL; CH471067; EAW90887.1; -; Genomic_DNA. DR EMBL; BC032016; AAH32016.1; -; mRNA. DR CCDS; CCDS1292.1; -. DR PIR; A38228; A38228. DR PIR; S62367; S51130. DR RefSeq; NP_001002294.1; NM_001002294.2. DR RefSeq; NP_008825.4; NM_006894.5. DR UniGene; Hs.445350; -. DR ProteinModelPortal; P31513; -. DR SMR; P31513; 3-440. DR STRING; 9606.ENSP00000356729; -. DR DrugBank; DB00918; Almotriptan. DR DrugBank; DB00501; Cimetidine. DR DrugBank; DB00363; Clozapine. DR DrugBank; DB00250; Dapsone. DR DrugBank; DB01254; Dasatinib. DR DrugBank; DB00334; Olanzapine. DR DrugBank; DB00675; Tamoxifen. DR DrugBank; DB05294; Vandetanib. DR DrugBank; DB00582; Voriconazole. DR PhosphoSite; P31513; -. DR BioMuta; FMO3; -. DR DMDM; 6166183; -. DR PaxDb; P31513; -. DR PRIDE; P31513; -. DR DNASU; 2328; -. DR Ensembl; ENST00000367755; ENSP00000356729; ENSG00000007933. DR GeneID; 2328; -. DR KEGG; hsa:2328; -. DR UCSC; uc001ghh.3; human. DR CTD; 2328; -. DR GeneCards; FMO3; -. DR GeneReviews; FMO3; -. DR HGNC; HGNC:3771; FMO3. DR HPA; HPA008065; -. DR HPA; HPA013750; -. DR MIM; 136132; gene. DR MIM; 602079; phenotype. DR neXtProt; NX_P31513; -. DR Orphanet; 35056; Trimethylaminuria. DR PharmGKB; PA166; -. DR eggNOG; KOG1399; Eukaryota. DR eggNOG; COG2072; LUCA. DR GeneTree; ENSGT00760000119232; -. DR HOGENOM; HOG000076537; -. DR HOVERGEN; HBG002037; -. DR InParanoid; P31513; -. DR KO; K00485; -. DR OMA; YKEPGIF; -. DR OrthoDB; EOG7GXPB6; -. DR PhylomeDB; P31513; -. DR TreeFam; TF105285; -. DR BioCyc; MetaCyc:HS00223-MONOMER; -. DR BRENDA; 1.14.13.148; 2681. DR BRENDA; 1.14.13.8; 2681. DR Reactome; R-HSA-217271; FMO oxidises nucleophiles. DR Reactome; R-HSA-5579019; Defective FMO3 causes Trimethylaminuria (TMAU). DR SABIO-RK; P31513; -. DR GeneWiki; Flavin_containing_monooxygenase_3; -. DR GenomeRNAi; 2328; -. DR NextBio; 9447; -. DR PRO; PR:P31513; -. DR Proteomes; UP000005640; Chromosome 1. DR Bgee; P31513; -. DR CleanEx; HS_FMO3; -. DR ExpressionAtlas; P31513; baseline and differential. DR Genevisible; P31513; HS. DR GO; GO:0005789; C:endoplasmic reticulum membrane; TAS:Reactome. DR GO; GO:0016021; C:integral component of membrane; IEA:UniProtKB-KW. DR GO; GO:0043231; C:intracellular membrane-bounded organelle; TAS:ProtInc. DR GO; GO:0050660; F:flavin adenine dinucleotide binding; IEA:InterPro. DR GO; GO:0004499; F:N,N-dimethylaniline monooxygenase activity; IBA:GO_Central. DR GO; GO:0050661; F:NADP binding; IEA:InterPro. DR GO; GO:0034899; F:trimethylamine monooxygenase activity; IEA:UniProtKB-EC. DR GO; GO:0017144; P:drug metabolic process; IBA:GO_Central. DR GO; GO:0055114; P:oxidation-reduction process; IBA:GO_Central. DR GO; GO:0044281; P:small molecule metabolic process; TAS:Reactome. DR GO; GO:0006805; P:xenobiotic metabolic process; TAS:Reactome. DR Gene3D; 3.50.50.60; -; 4. DR InterPro; IPR012143; DiMe-aniline_mOase. DR InterPro; IPR023753; FAD/NAD-binding_dom. 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 Complete proteome; Direct protein sequencing; Disease mutation; KW Endoplasmic reticulum; FAD; Flavoprotein; Membrane; Microsome; KW Monooxygenase; NADP; Oxidoreductase; Phosphoprotein; Polymorphism; KW Reference proteome; Transmembrane. FT INIT_MET 1 1 Removed. {ECO:0000269|PubMed:9224773}. FT CHAIN 2 532 Dimethylaniline monooxygenase [N-oxide- FT forming] 3. FT /FTId=PRO_0000147654. FT NP_BIND 9 14 FAD. {ECO:0000255}. FT NP_BIND 191 196 NADP. {ECO:0000255}. FT MOD_RES 401 401 Phosphoserine. FT {ECO:0000250|UniProtKB:P97501}. FT VARIANT 24 24 E -> D (modest increase in catalytic FT efficiency toward trimethylamine, FT methimazole, ethylenethiourea and FT sulindac). {ECO:0000269|PubMed:17050781}. FT /FTId=VAR_042705. FT VARIANT 32 32 E -> K (in TMAU). FT {ECO:0000269|PubMed:12893987}. FT /FTId=VAR_037306. FT VARIANT 52 52 A -> T (in TMAU). FT {ECO:0000269|PubMed:10479479}. FT /FTId=VAR_008146. FT VARIANT 61 61 N -> K (loss of activity). FT {ECO:0000269|PubMed:17050781}. FT /FTId=VAR_042706. FT VARIANT 61 61 N -> S (in TMAU; more than 90% reduction FT in catalytic efficiency toward FT trimethylamine, benzydamine and methyl p- FT tolyl sulfide). FT {ECO:0000269|PubMed:11191884, FT ECO:0000269|PubMed:17531949}. FT /FTId=VAR_037307. FT VARIANT 66 66 M -> I (in TMAU; loss of activity; FT affects FAD binding). FT {ECO:0000269|PubMed:10338091, FT ECO:0000269|PubMed:17531949, FT ECO:0000269|PubMed:9536088}. FT /FTId=VAR_002423. FT VARIANT 132 132 D -> H (in dbSNP:rs12072582). FT {ECO:0000269|PubMed:12527699, FT ECO:0000269|Ref.4}. FT /FTId=VAR_015364. FT VARIANT 153 153 P -> L (in TMAU; 90% reduction in FT catalytic efficiency toward FT trimethylamine and benzydamine; 34% FT reduction in catalytic efficiency toward FT methyl p-tolyl sulfide; nearly no effect FT on affinity for these substrates). FT {ECO:0000269|PubMed:11191884, FT ECO:0000269|PubMed:17531949, FT ECO:0000269|PubMed:9536088}. FT /FTId=VAR_002424. FT VARIANT 158 158 E -> K (35%, 45% and 71% increase in FT catalytic efficiency toward FT trimethylamine, benzydamine and methyl p- FT tolyl sulfide, respectively; FT dbSNP:rs2266782). FT {ECO:0000269|PubMed:10479479, FT ECO:0000269|PubMed:12527699, FT ECO:0000269|PubMed:17050781, FT ECO:0000269|PubMed:17531949, FT ECO:0000269|PubMed:9536088, FT ECO:0000269|Ref.4}. FT /FTId=VAR_002425. FT VARIANT 198 198 D -> E. {ECO:0000269|PubMed:15618753}. FT /FTId=VAR_018345. FT VARIANT 205 205 R -> C (in dbSNP:rs28363549). FT {ECO:0000269|PubMed:15618753, FT ECO:0000269|Ref.4}. FT /FTId=VAR_018346. FT VARIANT 257 257 V -> M (65% increase in catalytic FT efficiency toward trimethylamine and 60% FT reduction toward benzydamine and methyl FT p-tolyl sulfide; dbSNP:rs1736557). FT {ECO:0000269|PubMed:12527699, FT ECO:0000269|PubMed:15489334, FT ECO:0000269|PubMed:17050781, FT ECO:0000269|PubMed:17531949, FT ECO:0000269|PubMed:9536088, FT ECO:0000269|Ref.4}. FT /FTId=VAR_002426. FT VARIANT 277 277 V -> A (in dbSNP:rs2066530). FT {ECO:0000269|Ref.4}. FT /FTId=VAR_014845. FT VARIANT 308 308 E -> G (16% reduction in catalytic FT efficiency toward trimethylamine and 40% FT increase toward benzydamine and methyl p- FT tolyl sulfide; dbSNP:rs2266780). FT {ECO:0000269|PubMed:10479479, FT ECO:0000269|PubMed:17050781, FT ECO:0000269|PubMed:17531949, FT ECO:0000269|PubMed:9536088, FT ECO:0000269|Ref.4}. FT /FTId=VAR_002427. FT VARIANT 360 360 L -> P (in dbSNP:rs28363581). FT {ECO:0000269|PubMed:12527699, FT ECO:0000269|Ref.4}. FT /FTId=VAR_015365. FT VARIANT 362 362 E -> Q (in dbSNP:rs2066532). FT {ECO:0000269|PubMed:12527699, FT ECO:0000269|Ref.4}. FT /FTId=VAR_014846. FT VARIANT 387 387 R -> L (in TMAU; dbSNP:rs72549331). FT {ECO:0000269|PubMed:10479479}. FT /FTId=VAR_008147. FT VARIANT 416 416 K -> N (2-fold decrease in affinity for FT trimethylamine; 3-fold decrease in FT catalytic efficiency toward methimazole; FT 3-fold increase in catalytic efficiency FT toward sulindac; 30% increase in FT catalytic efficiency toward FT ethylenethiourea). FT {ECO:0000269|PubMed:17050781}. FT /FTId=VAR_042707. FT VARIANT 434 434 M -> I (in TMAU; profoundly alters enzyme FT function). {ECO:0000269|PubMed:11191884}. FT /FTId=VAR_037308. FT VARIANT 492 492 R -> W (in TMAU; loss of activity; FT affects FAD binding). FT {ECO:0000269|PubMed:10338091, FT ECO:0000269|PubMed:11191884, FT ECO:0000269|PubMed:17531949}. FT /FTId=VAR_008145. FT VARIANT 503 503 G -> R. {ECO:0000269|PubMed:12527699}. FT /FTId=VAR_015366. FT CONFLICT 298 298 S -> T (in Ref. 1; AAA86284). FT {ECO:0000305}. FT CONFLICT 369 369 I -> L (in Ref. 1; AAA86284). FT {ECO:0000305}. FT CONFLICT 400 405 PSMEDM -> GPFYGKTL (in Ref. 1; AAA86284). FT {ECO:0000305}. FT CONFLICT 410 410 N -> I (in Ref. 1; AAA86284). FT {ECO:0000305}. FT CONFLICT 418 419 KW -> ANG (in Ref. 1; AAA86284). FT {ECO:0000305}. FT CONFLICT 444 445 KP -> T (in Ref. 1; AAA86284). FT {ECO:0000305}. FT CONFLICT 449 449 W -> M (in Ref. 1; AAA86284). FT {ECO:0000305}. FT CONFLICT 454 454 D -> G (in Ref. 1; AAA86284). FT {ECO:0000305}. FT CONFLICT 461 462 VY -> L (in Ref. 1; AAA86284). FT {ECO:0000305}. FT CONFLICT 478 478 Q -> S (in Ref. 1; AAA86284). FT {ECO:0000305}. FT CONFLICT 486 486 I -> M (in Ref. 2; CAA87632). FT {ECO:0000305}. SQ SEQUENCE 532 AA; 60033 MW; 729E41D53EFC4110 CRC64; MGKKVAIIGA GVSGLASIRS CLEEGLEPTC FEKSNDIGGL WKFSDHAEEG RASIYKSVFS NSSKEMMCFP DFPFPDDFPN FMHNSKIQEY IIAFAKEKNL LKYIQFKTFV SSVNKHPDFA TTGQWDVTTE RDGKKESAVF DAVMVCSGHH VYPNLPKESF PGLNHFKGKC FHSRDYKEPG VFNGKRVLVV GLGNSGCDIA TELSRTAEQV MISSRSGSWV MSRVWDNGYP WDMLLVTRFG TFLKNNLPTA ISDWLYVKQM NARFKHENYG LMPLNGVLRK EPVFNDELPA SILCGIVSVK PNVKEFTETS AIFEDGTIFE GIDCVIFATG YSFAYPFLDE SIIKSRNNEI ILFKGVFPPL LEKSTIAVIG FVQSLGAAIP TVDLQSRWAA QVIKGTCTLP SMEDMMNDIN EKMEKKRKWF GKSETIQTDY IVYMDELSSF IGAKPNIPWL FLTDPKLAME VYFGPCSPYQ FRLVGPGQWP GARNAILTQW DRSLKPMQTR VVGRLQKPCF FFHWLKLFAI PILLIAVFLV LT //