ID FMO1_HUMAN Reviewed; 532 AA. AC Q01740; A8K248; B7Z3P4; Q5QPT2; Q9UJC2; DT 01-JUL-1993, integrated into UniProtKB/Swiss-Prot. DT 23-JAN-2007, sequence version 3. DT 11-NOV-2015, entry version 143. DE RecName: Full=Dimethylaniline monooxygenase [N-oxide-forming] 1; DE EC=1.14.13.8; DE AltName: Full=Dimethylaniline oxidase 1; DE AltName: Full=Fetal hepatic flavin-containing monooxygenase 1; DE Short=FMO 1; GN Name=FMO1; 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] (ISOFORM 1). RC TISSUE=Liver; RX PubMed=1712018; RA Dolphin C.T., Shephard E.A., Povey S., Palmer C.N.A., Ziegler D.M., RA Ayesh R., Smith R.L., Phillips I.R.; RT "Cloning, primary sequence, and chromosomal mapping of a human flavin- RT containing monooxygenase (FMO1)."; RL J. Biol. Chem. 266:12379-12385(1991). RN [2] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND VARIANTS GLN-223; THR-227; RP VAL-303; VAL-322; LEU-327; ARG-373 AND HIS-474. RG NIEHS SNPs program; RL Submitted (JAN-2005) to the EMBL/GenBank/DDBJ databases. RN [3] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 2). RC TISSUE=Thalamus; 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 [4] 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 [5] 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 [6] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1). RC TISSUE=Colon; 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 [7] RP VARIANTS GLN-97; THR-303 AND VAL-303. 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). CC -!- FUNCTION: This protein is involved in the oxidative metabolism of CC a variety of xenobiotics such as drugs and pesticides. Form I CC catalyzes the N-oxygenation of secondary and tertiary amines. CC -!- CATALYTIC ACTIVITY: N,N-dimethylaniline + NADPH + O(2) = N,N- CC dimethylaniline N-oxide + NADP(+) + H(2)O. CC -!- COFACTOR: CC Name=FAD; Xref=ChEBI:CHEBI:57692; CC -!- SUBCELLULAR LOCATION: Microsome membrane. Endoplasmic reticulum CC membrane. CC -!- ALTERNATIVE PRODUCTS: CC Event=Alternative splicing; Named isoforms=2; CC Name=1; CC IsoId=Q01740-1; Sequence=Displayed; CC Name=2; CC IsoId=Q01740-2; Sequence=VSP_054543; CC Note=No experimental confirmation available.; CC -!- TISSUE SPECIFICITY: Expressed mainly in fetal liver, adult kidney CC and, to a lesser extent, the intestine. CC -!- SIMILARITY: Belongs to the FMO family. {ECO:0000305}. CC -!- WEB RESOURCE: Name=NIEHS-SNPs; CC URL="http://egp.gs.washington.edu/data/fmo1/"; 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; M64082; AAA52457.1; -; mRNA. DR EMBL; AY879266; AAW56076.1; -; Genomic_DNA. DR EMBL; AK290113; BAF82802.1; -; mRNA. DR EMBL; AK296198; BAH12280.1; -; mRNA. DR EMBL; AL021026; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; AL445673; CAI21383.1; -; Genomic_DNA. DR EMBL; AL031274; CAI21383.1; JOINED; Genomic_DNA. DR EMBL; AL031274; CAI22846.1; -; Genomic_DNA. DR EMBL; AL445673; CAI22846.1; JOINED; Genomic_DNA. DR EMBL; CH471067; EAW90892.1; -; Genomic_DNA. DR EMBL; BC047129; AAH47129.1; -; mRNA. DR CCDS; CCDS1294.1; -. [Q01740-1] DR CCDS; CCDS60351.1; -. [Q01740-2] DR PIR; A40876; A40876. DR RefSeq; NP_001269621.1; NM_001282692.1. DR RefSeq; NP_001269622.1; NM_001282693.1. [Q01740-1] DR RefSeq; NP_001269623.1; NM_001282694.1. [Q01740-2] DR RefSeq; NP_002012.1; NM_002021.2. [Q01740-1] DR UniGene; Hs.1424; -. DR ProteinModelPortal; Q01740; -. DR SMR; Q01740; 1-442. DR STRING; 9606.ENSP00000346901; -. DR DrugBank; DB00185; Cevimeline. DR DrugBank; DB00501; Cimetidine. DR DrugBank; DB04871; Lorcaserin. DR DrugBank; DB00675; Tamoxifen. DR DrugBank; DB05294; Vandetanib. DR DrugBank; DB00582; Voriconazole. DR PhosphoSite; Q01740; -. DR DMDM; 399505; -. DR PaxDb; Q01740; -. DR PRIDE; Q01740; -. DR DNASU; 2326; -. DR Ensembl; ENST00000354841; ENSP00000346901; ENSG00000010932. [Q01740-1] DR Ensembl; ENST00000367750; ENSP00000356724; ENSG00000010932. [Q01740-1] DR Ensembl; ENST00000402921; ENSP00000385543; ENSG00000010932. [Q01740-2] DR Ensembl; ENST00000617670; ENSP00000481732; ENSG00000010932. [Q01740-1] DR GeneID; 2326; -. DR KEGG; hsa:2326; -. DR UCSC; uc001ghl.3; human. [Q01740-1] DR UCSC; uc010pme.2; human. DR CTD; 2326; -. DR GeneCards; FMO1; -. DR H-InvDB; HIX0028548; -. DR HGNC; HGNC:3769; FMO1. DR HPA; HPA023680; -. DR MIM; 136130; gene. DR neXtProt; NX_Q01740; -. DR PharmGKB; PA165; -. DR eggNOG; KOG1399; Eukaryota. DR eggNOG; COG2072; LUCA. DR GeneTree; ENSGT00760000119232; -. DR HOGENOM; HOG000076537; -. DR HOVERGEN; HBG002037; -. DR InParanoid; Q01740; -. DR KO; K00485; -. DR OMA; PSVMIEE; -. DR PhylomeDB; Q01740; -. DR TreeFam; TF105285; -. DR BRENDA; 1.14.13.8; 2681. DR Reactome; R-HSA-217271; FMO oxidises nucleophiles. DR GeneWiki; Flavin_containing_monooxygenase_1; -. DR GenomeRNAi; 2326; -. DR NextBio; 35479295; -. DR PRO; PR:Q01740; -. DR Proteomes; UP000005640; Chromosome 1. DR Bgee; Q01740; -. DR CleanEx; HS_FMO1; -. DR ExpressionAtlas; Q01740; baseline and differential. DR Genevisible; Q01740; HS. DR GO; GO:0005788; C:endoplasmic reticulum lumen; TAS:Reactome. 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:0050660; F:flavin adenine dinucleotide binding; IEA:InterPro. DR GO; GO:0004497; F:monooxygenase activity; IDA:MGI. DR GO; GO:0004499; F:N,N-dimethylaniline monooxygenase activity; IDA:BHF-UCL. DR GO; GO:0050661; F:NADP binding; IEA:InterPro. DR GO; GO:0017144; P:drug metabolic process; IBA:GO_Central. 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:0032496; P:response to lipopolysaccharide; IEA:Ensembl. DR GO; GO:0006970; P:response to osmotic stress; IEA:Ensembl. DR GO; GO:0044281; P:small molecule metabolic process; TAS:Reactome. DR GO; GO:0009404; P:toxin metabolic process; IDA:BHF-UCL. DR GO; GO:0006805; P:xenobiotic metabolic process; TAS:Reactome. DR Gene3D; 3.50.50.60; -; 2. 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; IPR002253; Flavin_mOase_1. DR Pfam; PF00743; FMO-like; 1. DR PIRSF; PIRSF000332; FMO; 1. DR PRINTS; PR00370; FMOXYGENASE. DR PRINTS; PR01121; FMOXYGENASE1. DR SUPFAM; SSF51905; SSF51905; 2. PE 2: Evidence at transcript level; KW Acetylation; Alternative splicing; Complete proteome; KW Endoplasmic reticulum; FAD; Flavoprotein; Membrane; Microsome; KW Monooxygenase; NADP; Oxidoreductase; Polymorphism; Reference proteome; KW Transmembrane. FT INIT_MET 1 1 Removed. {ECO:0000250|UniProtKB:P16549}. FT CHAIN 2 532 Dimethylaniline monooxygenase [N-oxide- FT forming] 1. FT /FTId=PRO_0000147639. FT NP_BIND 9 14 FAD. {ECO:0000255}. FT NP_BIND 191 196 NADP. {ECO:0000255}. FT MOD_RES 2 2 N-acetylalanine. FT {ECO:0000250|UniProtKB:P16549}. FT VAR_SEQ 45 107 Missing (in isoform 2). FT {ECO:0000303|PubMed:14702039}. FT /FTId=VSP_054543. FT VARIANT 97 97 H -> Q (in dbSNP:rs56841822). FT {ECO:0000269|PubMed:12527699}. FT /FTId=VAR_015358. FT VARIANT 223 223 R -> Q (in dbSNP:rs16864310). FT {ECO:0000269|Ref.2}. FT /FTId=VAR_022204. FT VARIANT 227 227 S -> T. {ECO:0000269|Ref.2}. FT /FTId=VAR_022205. FT VARIANT 303 303 I -> T (in dbSNP:rs28360418). FT {ECO:0000269|PubMed:12527699}. FT /FTId=VAR_015359. FT VARIANT 303 303 I -> V (in dbSNP:rs16864314). FT {ECO:0000269|PubMed:12527699, FT ECO:0000269|Ref.2}. FT /FTId=VAR_015360. FT VARIANT 322 322 I -> V (in dbSNP:rs28360419). FT {ECO:0000269|Ref.2}. FT /FTId=VAR_022206. FT VARIANT 327 327 F -> L (in dbSNP:rs28360420). FT {ECO:0000269|Ref.2}. FT /FTId=VAR_022207. FT VARIANT 373 373 K -> R (in dbSNP:rs28360421). FT {ECO:0000269|Ref.2}. FT /FTId=VAR_022208. FT VARIANT 474 474 R -> H (in dbSNP:rs28360433). FT {ECO:0000269|Ref.2}. FT /FTId=VAR_022209. SQ SEQUENCE 532 AA; 60311 MW; 627B855F38C2EB6D CRC64; MAKRVAIVGA GVSGLASIKC CLEEGLEPTC FERSDDLGGL WRFTEHVEEG RASLYKSVVS NSCKEMSCYS DFPFPEDYPN YVPNSQFLEY LKMYANHFDL LKHIQFKTKV CSVTKCSDSA VSGQWEVVTM HEEKQESAIF DAVMVCTGFL TNPYLPLDSF PGINAFKGQY FHSRQYKHPD IFKDKRVLVI GMGNSGTDIA VEASHLAEKV FLSTTGGGWV ISRIFDSGYP WDMVFMTRFQ NMLRNSLPTP IVTWLMERKI NNWLNHANYG LIPEDRTQLK EFVLNDELPG RIITGKVFIR PSIKEVKENS VIFNNTSKEE PIDIIVFATG YTFAFPFLDE SVVKVEDGQA SLYKYIFPAH LQKPTLAIIG LIKPLGSMIP TGETQARWAV RVLKGVNKLP PPSVMIEEIN ARKENKPSWF GLCYCKALQS DYITYIDELL TYINAKPNLF SMLLTDPHLA LTVFFGPCSP YQFRLTGPGK WEGARNAIMT QWDRTFKVIK ARVVQESPSP FESFLKVFSF LALLVAIFLI FL //