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UniProtKB/Swiss-Prot entry P31512


[Entry info] [Name and origin] [References] [Comments] [Cross-references] [Keywords] [Features] [Sequence] [Tools]

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Entry information
Entry name FMO4_HUMAN
Primary accession number P31512
Secondary accession numbers None
Integrated into Swiss-Prot on July 1, 1993
Sequence was last modified on January 23, 2007 (Sequence version 3)
Annotations were last modified on    November 25, 2008 (Entry version 84)
Name and origin of the protein
Protein name Dimethylaniline monooxygenase [N-oxide-forming] 4
Synonyms EC 1.14.13.8
Hepatic flavin-containing monooxygenase 4
FMO 4
Dimethylaniline oxidase 4
Gene name
Name: FMO4
Synonyms: FMO2
From
Homo sapiens (Human) [TaxID: 9606] 
Taxonomy Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo.
Protein existence 2: Evidence at transcript level;
References
[1]
NUCLEOTIDE SEQUENCE [MRNA].
TISSUE=Liver;
PubMed=1417778 [NCBI, ExPASy, EBI, Israel, Japan]
Dolphin C.T., Shephard E.A., Povey S., Smith R.L., Phillips I.R.;
"Cloning, primary sequence and chromosomal localization of human FMO2, a new member of the flavin-containing mono-oxygenase family.";
Biochem. J. 287:261-267(1992).
[2]
NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND VARIANTS ALA-323; SER-372; LEU-536 AND ARG-544.
Livingston R.J., Rieder M.J., Chung M.-W., Downing T.K., Olson A.N., Nguyen C.P., Gildersleeve H., Cassidy C.M., Johnson E.J., Swanson J.E., McFarland I., Yool B., Park C., Nickerson D.A.;
"NIEHS-SNPs, environmental genome project, NIEHS ES15478, Department of Genome Sciences, Seattle, WA (URL: http://egp.gs.washington.edu).";
Submitted (JAN-2005) to the EMBL/GenBank/DDBJ databases.
[3]
NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
DOI=10.1038/nature04727; PubMed=16710414 [NCBI, ExPASy, EBI, Israel, Japan]
Gregory S.G., Barlow K.F., McLay K.E., Kaul R., Swarbreck D., Dunham A., Scott C.E., Howe K.L., Woodfine K., Spencer C.C.A., Jones M.C., Gillson C., Searle S., Zhou Y., Kokocinski F., McDonald L., Evans R., Phillips K., Atkinson A., Cooper R., Jones C., Hall R.E., Andrews T.D., Lloyd C., Ainscough R., Almeida J.P., Ambrose K.D., Anderson F., Andrew R.W., Ashwell R.I.S., Aubin K., Babbage A.K., Bagguley C.L., Bailey J., Beasley H., Bethel G., Bird C.P., Bray-Allen S., Brown J.Y., Brown A.J., Buckley D., Burton J., Bye J., Carder C., Chapman J.C., Clark S.Y., Clarke G., Clee C., Cobley V., Collier R.E., Corby N., Coville G.J., Davies J., Deadman R., Dunn M., Earthrowl M., Ellington A.G., Errington H., Frankish A., Frankland J., French L., Garner P., Garnett J., Gay L., Ghori M.R.J., Gibson R., Gilby L.M., Gillett W., Glithero R.J., Grafham D.V., Griffiths C., Griffiths-Jones S., Grocock R., Hammond S., Harrison E.S.I., Hart E., Haugen E., Heath P.D., Holmes S., Holt K., Howden P.J., Hunt A.R., Hunt S.E., Hunter G., Isherwood J., James R., Johnson C., Johnson D., Joy A., Kay M., Kershaw J.K., Kibukawa M., Kimberley A.M., King A., Knights A.J., Lad H., Laird G., Lawlor S., Leongamornlert D.A., Lloyd D.M., Loveland J., Lovell J., Lush M.J., Lyne R., Martin S., Mashreghi-Mohammadi M., Matthews L., Matthews N.S.W., McLaren S., Milne S., Mistry S., Moore M.J.F., Nickerson T., O'Dell C.N., Oliver K., Palmeiri A., Palmer S.A., Parker A., Patel D., Pearce A.V., Peck A.I., Pelan S., Phelps K., Phillimore B.J., Plumb R., Rajan J., Raymond C., Rouse G., Saenphimmachak C., Sehra H.K., Sheridan E., Shownkeen R., Sims S., Skuce C.D., Smith M., Steward C., Subramanian S., Sycamore N., Tracey A., Tromans A., Van Helmond Z., Wall M., Wallis J.M., White S., Whitehead S.L., Wilkinson J.E., Willey D.L., Williams H., Wilming L., Wray P.W., Wu Z., Coulson A., Vaudin M., Sulston J.E., Durbin R.M., Hubbard T., Wooster R., Dunham I., Carter N.P., McVean G., Ross M.T., Harrow J., Olson M.V., Beck S., Rogers J., Bentley D.R.;
"The DNA sequence and biological annotation of human chromosome 1.";
Nature 441:315-321(2006).
[4]
NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
TISSUE=Skin;
DOI=10.1101/gr.2596504; PubMed=15489334 [NCBI, ExPASy, EBI, Israel, Japan]
The MGC Project Team;
"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC).";
Genome Res. 14:2121-2127(2004).
[5]
VARIANTS THR-37; ALA-323 AND GLN-339.
DOI=10.1124/dmd.31.2.187; PubMed=12527699 [NCBI, ExPASy, EBI, Israel, Japan]
Furnes B., Feng J., Sommer S.S., Schlenk D.;
"Identification of novel variants of the flavin-containing monooxygenase gene family in African Americans.";
Drug Metab. Dispos. 31:187-193(2003).
Comments
  • FUNCTION: This protein is involved in the oxidative metabolism of a variety of xenobiotics such as drugs and pesticides.
  • CATALYTIC ACTIVITY: N,N-dimethylaniline + NADPH + O2 = N,N-dimethylaniline N-oxide + NADP+ + H2O.
  • COFACTOR: FAD.
  • SUBCELLULAR LOCATION: Microsome membrane. Endoplasmic reticulum membrane.
  • TISSUE SPECIFICITY: Liver.
  • DISEASE: Metabolic oxidation of diet-derived amino-trimethylamine (TMA) is mediated by FMO. Due to a polymorphism a small subset of human population has a reduced TMA N-oxidation capacity. Such individuals excrete relatively large amounts of TMA in their urine, sweat, and breath, and exhibit a fishy body odor characteristic of the malodorous free amine, leading to the designation fish-odor syndrome.
  • SIMILARITY: Belongs to the FMO family.
  • CAUTION: Was originally termed FMO2.
Copyright
Copyrighted by the UniProt Consortium, see http://www.uniprot.org/terms. Distributed under the Creative Commons Attribution-NoDerivs License.
Cross-references
Sequence databases
EMBL
Z11737; CAA77797.1; -; mRNA.[EMBL / GenBank / DDBJ] [CoDingSequence]
AY882422; AAW56938.1; -; Genomic_DNA.[EMBL / GenBank / DDBJ] [CoDingSequence]
AL031274; CAB42008.1; -; Genomic_DNA.[EMBL / GenBank / DDBJ] [CoDingSequence]
BC002780; AAH02780.1; -; mRNA.[EMBL / GenBank / DDBJ] [CoDingSequence]
PIR S29125; S29125.
RefSeq NP_002013.1; -.
UniGene Hs.386502
3D structure databases
ModBase P31512.
PTM databases
PhosphoSite P31512; -.
Polymorphism databases
NIEHS-SNPs FMO4.
Organism-specific databases
H-InvDB HIX0001327; -.
HGNC HGNC:3772; FMO4.
GenAtlas FMO4.
MIM 136131; gene. [NCBI / EBI]
PharmGKB PA28188; -.
GeneCards P31512.
Gene expression databases
ArrayExpress P31512; -.
CleanEx HS_FMO2; -.
HS_FMO4; -.
GermOnline ENSG00000076258; Homo sapiens.
Ontologies
GO
GO:0016021; Cellular component: integral to membrane (inferred from electronic annotation from UniProtKB-KW).
GO:0031227; Cellular component: intrinsic to endoplasmic reticulum membrane (inferred from electronic annotation from InterPro).
GO:0005792; Cellular component: microsome (non-traceable author statement from UniProtKB).
GO:0050660; Molecular function: FAD binding (inferred from electronic annotation from InterPro).
GO:0004499; Molecular function: flavin-containing monooxygenase activity (non-traceable author statement from UniProtKB).
GO:0050661; Molecular function: NADP binding (inferred from electronic annotation from InterPro).
GO:0055114; Biological process: oxidation reduction (inferred from electronic annotation from UniProtKB-KW).
GO:0006805; Biological process: xenobiotic metabolic process (non-traceable author statement from UniProtKB).
QuickGo view.
Family and domain databases
InterPro IPR012143; dManiline_mOase.
IPR000960; Flavin_mOase.
IPR002256; Flavin_mOase_4.
Graphical view of domain structure.
Pfam PF00743; FMO-like; 1.
Pfam graphical view of domain structure.
PIRSF PIRSF000332; FMO; 1.
PRINTS PR00370; FMOXYGENASE.
PR01124; FMOXYGENASE4.
ProDom PD000139; FAD_pyr_redox; 1.
[Domain structure / List of seq. sharing at least 1 domain]
ProtoNet P31512.
Genome annotation databases
Ensembl ENSG00000076258; Homo sapiens. [Contig view]
GeneID 2329; -.
KEGG hsa:2329; -.
Phylogenomic databases
HOGENOM P31512; -.
HOVERGEN P31512; -.
Other
NextBio 9453; -.
SOURCE FMO4; Homo sapiens.
UniRef View cluster of proteins with at least 50% / 90% / 100% identity.
Keywords
Acetylation; Endoplasmic reticulum; FAD; Flavoprotein; Membrane; Microsome; Monooxygenase; NADP; Oxidoreductase; Polymorphism; Transmembrane.
Features
SEVIEWER logo Feature table viewer FT aligner logo Feature aligner
KeyFrom   To Length Description FTId
INIT_MET   1     1        Removed (By similarity). 
CHAIN   2   558  557     Dimethylaniline monooxygenase [N-oxide-forming] 4. PRO_0000147660
TRANSMEM   517   531  15     Potential. 
NP_BIND   9    14  6     FAD (Potential). 
NP_BIND   191   196  6     NADP (Potential). 
MOD_RES   2     2        N-acetylalanine (By similarity). 
VARIANT   37    37  1     I -> T. VAR_015367 
VARIANT   323   323  1     V -> A. VAR_015368 
VARIANT   339   339  1     E -> Q. VAR_015369 
VARIANT   372   372  1     G -> S. VAR_022305 
VARIANT   536   536  1     F -> L. VAR_022306 
VARIANT   544   544  1     L -> R. VAR_022307 
Sequence information
Length: 558 AA [This is the length of the unprocessed precursor] Molecular weight: 63343 Da [This is the MW of the unprocessed precursor] CRC64: 6981AE9180C07802 [This is a checksum on the sequence]
        10         20         30         40         50         60 
MAKKVAVIGA GVSGLSSIKC CVDEDLEPTC FERSDDIGGL WKFTESSKDG MTRVYKSLVT 

        70         80         90        100        110        120 
NVCKEMSCYS DFPFHEDYPN FMNHEKFWDY LQEFAEHFDL LKYIQFKTTV CSITKRPDFS 

       130        140        150        160        170        180 
ETGQWDVVTE TEGKQNRAVF DAVMVCTGHF LNPHLPLEAF PGIHKFKGQI LHSQEYKIPE 

       190        200        210        220        230        240 
GFQGKRVLVI GLGNTGGDIA VELSRTAAQV LLSTRTGTWV LGRSSDWGYP YNMMVTRRCC 

       250        260        270        280        290        300 
SFIAQVLPSR FLNWIQERKL NKRFNHEDYG LSITKGKKAK FIVNDELPNC ILCGAITMKT 

       310        320        330        340        350        360 
SVIEFTETSA VFEDGTVEEN IDVVIFTTGY TFSFPFFEEP LKSLCTKKIF LYKQVFPLNL 

       370        380        390        400        410        420 
ERATLAIIGL IGLKGSILSG TELQARWVTR VFKGLCKIPP SQKLMMEATE KEQLIKRGVF 

       430        440        450        460        470        480 
KDTSKDKFDY IAYMDDIAAC IGTKPSIPLL FLKDPRLAWE VFFGPCTPYQ YRLMGPGKWD 

       490        500        510        520        530        540 
GARNAILTQW DRTLKPLKTR IVPDSSKPAS MSHYLKAWGA PVLLASLLLI CKSSLFLKLV 

       550 
RDKLQDRMSP YLVSLWRG 

P31512 in FASTA format

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