Reviewed, UniProtKB/Swiss-Prot P31512 (FMO4_HUMAN)

Names and origin

Protein names

Recommended name:
    Dimethylaniline monooxygenase [N-oxide-forming] 4
    EC=1.14.13.8
Alternative name(s):
    Hepatic flavin-containing monooxygenase 4
      Short name=FMO 4
    Dimethylaniline oxidase 4

Gene names

Name:	FMO4
Synonyms:	FMO2

Organism

Homo sapiens (Human)

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo

Protein attributes

Sequence length	558 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is further processed into a mature form.
Protein existence	Evidence at transcript level.

General annotation (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 + O(2) = N,N-dimethylaniline N-oxide + NADP(+) + H(2)O.
Cofactor	FAD.
Subcellular location	Microsome membrane. Endoplasmic reticulum membrane.
Tissue specificity	Liver.
Involvement in 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.
Sequence similarities	Belongs to the FMO family.
Caution	Was originally termed FMO2.

Ontologies

Keywords
Cellular component	Endoplasmic reticulum Membrane Microsome
Coding sequence diversity	Polymorphism
Domain	Transmembrane
Ligand	FAD Flavoprotein NADP
Molecular function	Monooxygenase Oxidoreductase
PTM	Acetylation
Gene Ontology (GO)
Biological process	oxidation reduction Inferred from electronic annotation. Source: UniProtKB-KW xenobiotic metabolic process Non-traceable author statement. Source: UniProtKB
Cellular component	integral to membrane Inferred from electronic annotation. Source: UniProtKB-KW intrinsic to endoplasmic reticulum membrane Inferred from electronic annotation. Source: InterPro microsome Non-traceable author statement. Source: UniProtKB
Molecular function	FAD binding Inferred from electronic annotation. Source: InterPro NADP binding Inferred from electronic annotation. Source: InterPro flavin-containing monooxygenase activity Ref.1 Non-traceable author statement. Source: UniProtKB
Complete GO annotation...

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Initiator methionine	1	1	Removed By similarity
	Chain	2 – 558	557	Dimethylaniline monooxygenase [N-oxide-forming] 4		PRO_0000147660
Regions
	Transmembrane	517 – 531	15	Potential
	Nucleotide binding	9 – 14	6	FAD Potential
	Nucleotide binding	191 – 196	6	NADP Potential
Amino acid modifications
	Modified residue	2	1	N-acetylalanine By similarity
Natural variations
	Natural variant	37	1	I → T		VAR_015367
	Natural variant	323	1	V → A		VAR_015368
	Natural variant	339	1	E → Q		VAR_015369
	Natural variant	372	1	G → S		VAR_022305
	Natural variant	536	1	F → L		VAR_022306
	Natural variant	544	1	L → R		VAR_022307

Sequences

	Sequence		Length	Mass (Da)
	P31512-1 [UniParc]. Last modified January 23, 2007. Version 3. Checksum: 6981AE9180C07802	FASTA	558	63,343
	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

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Cloning, primary sequence and chromosomal localization of human FMO2, a new member of the flavin-containing mono-oxygenase family." Dolphin C.T., Shephard E.A., Povey S., Smith R.L., Phillips I.R. Biochem. J. 287:261-267(1992) [PubMed: 1417778] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA]. Tissue: Liver.
[2]	"NIEHS-SNPs, environmental genome project, NIEHS ES15478, Department of Genome Sciences, Seattle, WA (URL: http://egp.gs.washington.edu)." 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. Submitted (JAN-2005) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA], VARIANTS ALA-323; SER-372; LEU-536 AND ARG-544.
[3]	"The DNA sequence and biological annotation of human chromosome 1." 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. Nature 441:315-321(2006) [PubMed: 16710414] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[4]	"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)." The MGC Project Team Genome Res. 14:2121-2127(2004) [PubMed: 15489334] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. Tissue: Skin.
[5]	"Identification of novel variants of the flavin-containing monooxygenase gene family in African Americans." Furnes B., Feng J., Sommer S.S., Schlenk D. Drug Metab. Dispos. 31:187-193(2003) [PubMed: 12527699] [Abstract] Cited for: VARIANTS THR-37; ALA-323 AND GLN-339.

Cross-references

Sequence databases
EMBLGenBankDDBJ	Z11737 mRNA. Translation: CAA77797.1. AY882422 Genomic DNA. Translation: AAW56938.1. AL031274 Genomic DNA. Translation: CAB42008.1. BC002780 mRNA. Translation: AAH02780.1.
PIR	S29125.
RefSeq	NP_002013.1.
UniGene	Hs.386502
3D structure databases
ModBase	Search...
PTM databases
PhosphoSite	P31512.
Polymorphism databases
NIEHS-SNPs	Search...
Genome annotation databases
Ensembl	ENSG00000076258. Homo sapiens. [Contig view]
GeneID	2329.
KEGG	hsa:2329.
Organism-specific databases
H-InvDB	HIX0001327.
HGNC	HGNC:3772. FMO4.
MIM	136131. gene.
PharmGKB	PA28188.
GenAtlas	Search...
GeneCards	Search...
Phylogenomic databases
HOGENOM	P31512.
HOVERGEN	P31512.
Gene expression databases
ArrayExpress	P31512.
CleanEx	HS_FMO2. HS_FMO4.
GermOnline	ENSG00000076258. Homo sapiens.
Family and domain databases
InterPro	IPR012143. dManiline_mOase. IPR000960. Flavin_mOase. IPR002256. Flavin_mOase_4. [Graphical view]
Pfam	PF00743. FMO-like. 1 hit. [Graphical view]
PIRSF	PIRSF000332. FMO. 1 hit.
PRINTS	PR00370. FMOXYGENASE. PR01124. FMOXYGENASE4.
ProDom	PD000139. FAD_pyr_redox. 1 hit. [Graphical view] [Entries sharing at least one domain]
ProtoNet	Search...
Other Resources
NextBio	9453.
SOURCE	Search...

Entry information

Entry name

FMO4_HUMAN

Accession

Primary (citable) accession number: P31512

Entry history

Integrated into UniProtKB/Swiss-Prot:	July 1, 1993
Last sequence update:	January 23, 2007
Last modified:	November 25, 2008
This is version 84 of the entry and version 3 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation project

HPI (Human Proteome Initiative)