Q99518 (FMO2_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Dimethylaniline monooxygenase [N-oxide-forming] 2
EC=1.14.13.8

Alternative name(s):
Dimethylaniline oxidase 2
FMO 1B1
Pulmonary flavin-containing monooxygenase 2
Short name=FMO 2

Gene names

Name:

FMO2

Organism

Homo sapiens (Human) [Reference proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Primates › Haplorrhini › Simiiformes › Catarrhini › Hominoidea › Hominidae › Homininae › Homo

Protein attributes

Sequence length	471 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is further processed into a mature form.
Protein existence	Evidence at protein level

General annotation (Comments)

Function	Catalyzes the N-oxidation of certain primary alkylamines to their oximes via an N-hydroxylamine intermediate. Inactive toward certain tertiary amines, such as imipramine or chloropromazine. Can catalyze the S-oxidation of methimazole. The truncated form is catalytically inactive. Ref.1
Catalytic activity	N,N-dimethylaniline + NADPH + O2 = N,N-dimethylaniline N-oxide + NADP+ + H2O.
Cofactor	FAD. Magnesium.
Subcellular location	Microsome membrane. Endoplasmic reticulum membrane Ref.1 Ref.7.
Tissue specificity	Expressed in lung (at protein level). Expressed predominantly in lung, and at a much lesser extent in kidney. Also expressed in fetal lung, but not in liver, kidney and brain. Ref.1 Ref.7
Post-translational modification	The truncated form is probably unable to fold correctly and is rapidly degraded. FMO2*1 is sumoylated at 'Lys-492'. Ref.8
Polymorphism	The sequence shown is that of the allele FMO2*2A. There are two alleles; one major, FMO2*2A (truncated form) and one minor, FMO2*1 (full-length form similar to the protein found in other mammals). A nonsense mutation transforms the Gln-472 of FMO2*1 in a premature stop codon. FMO2*2A occurs in essentially 100% of Caucasians and Asians. FMO2*1 is present at a frequency of approximately 4% to 13% in the sample of population of African descent. FMO2*2A is catalytically inactive.
Sequence similarities	Belongs to the FMO family.

Ontologies

Keywords
Cellular component	Endoplasmic reticulum Membrane Microsome
Coding sequence diversity	Polymorphism
Domain	Transmembrane
Ligand	FAD Flavoprotein Magnesium NADP
Molecular function	Monooxygenase Oxidoreductase
PTM	Acetylation Ubl conjugation
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	NADPH oxidation Inferred from direct assay Ref.1. Source: UniProtKB drug metabolic process Inferred from direct assay PubMed 11744609. Source: BHF-UCL organic acid metabolic process Inferred from direct assay PubMed 11744609. Source: BHF-UCL oxygen metabolic process Inferred from electronic annotation. Source: Compara toxin metabolic process Inferred from direct assay PubMed 11744609. Source: BHF-UCL xenobiotic metabolic process Inferred from direct assay PubMed 11744609. Source: BHF-UCL
Cellular_component	endoplasmic reticulum membrane Traceable author statement. Source: Reactome integral to membrane Inferred from electronic annotation. Source: UniProtKB-KW
Molecular_function	N,N-dimethylaniline monooxygenase activity Inferred from direct assay PubMed 11744609. Source: BHF-UCL NADP binding Inferred from electronic annotation. Source: InterPro flavin adenine dinucleotide binding Inferred from electronic annotation. Source: InterPro
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 – 471	470	Dimethylaniline monooxygenase [N-oxide-forming] 2		PRO_0000147646
Regions
	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	36	1	D → G. Ref.2 Ref.9 Corresponds to variant rs2020870 [ dbSNP | Ensembl ].		VAR_014840
	Natural variant	59	1	V → I. Ref.9 Corresponds to variant rs55708639 [ dbSNP | Ensembl ].		VAR_015361
	Natural variant	69	1	F → Y. Ref.2 Corresponds to variant rs28745274 [ dbSNP | Ensembl ].		VAR_022185
	Natural variant	81	1	F → S. Ref.2 Corresponds to variant rs2020860 [ dbSNP | Ensembl ].		VAR_014841
	Natural variant	182	1	F → S. Ref.2 Ref.9 Corresponds to variant rs2307492 [ dbSNP | Ensembl ].		VAR_014842
	Natural variant	195	1	S → L. Ref.2 Ref.9 Corresponds to variant rs2020862 [ dbSNP | Ensembl ].		VAR_014843
	Natural variant	238	1	R → Q. Ref.2 Ref.9 Corresponds to variant rs28369895 [ dbSNP | Ensembl ].		VAR_015362
	Natural variant	314	1	E → G. Ref.2 Corresponds to variant rs2020863 [ dbSNP | Ensembl ].		VAR_022186
	Natural variant	391	1	R → T. Ref.2 Ref.9 Corresponds to variant rs28369899 [ dbSNP | Ensembl ].		VAR_015363
	Natural variant	413	1	N → K. Ref.2 Ref.9 Corresponds to variant rs2020865 [ dbSNP | Ensembl ].		VAR_014844
	Natural variant	471	1	Y → YQYRLVGPGQWEGARNAIFT QKQRILKPLKTRALKDSSNF SVSFLLKILGLLAVVVAFFC QLQWS in allele FMO2*1.		VAR_064887
Experimental info
	Sequence conflict	71	1	D → DD in AAW82431. Ref.2

Sequences

	Sequence		Length	Mass (Da)
	Q99518 [UniParc]. Last modified April 5, 2011. Version 4. Checksum: AF87E304131BA703	FASTA	471	53,644
	10 20 30 40 50 60 MAKKVAVIGA GVSGLISLKC CVDEGLEPTC FERTEDIGGV WRFKENVEDG RASIYQSVVT 70 80 90 100 110 120 NTSKEMSCFS DFPMPEDFPN FLHNSKLLEY FRIFAKKFDL LKYIQFQTTV LSVRKCPDFS 130 140 150 160 170 180 SSGQWKVVTQ SNGKEQSAVF DAVMVCSGHH ILPHIPLKSF PGMERFKGQY FHSRQYKHPD 190 200 210 220 230 240 GFEGKRILVI GMGNSGSDIA VELSKNAAQV FISTRHGTWV MSRISEDGYP WDSVFHTRFR 250 260 270 280 290 300 SMLRNVLPRT AVKWMIEQQM NRWFNHENYG LEPQNKYIMK EPVLNDDVPS RLLCGAIKVK 310 320 330 340 350 360 STVKELTETS AIFEDGTVEE NIDVIIFATG YSFSFPFLED SLVKVENNMV SLYKYIFPAH 370 380 390 400 410 420 LDKSTLACIG LIQPLGSIFP TAELQARWVT RVFKGLCSLP SERTMMMDII KRNEKRIDLF 430 440 450 460 470 GESQSQTLQT NYVDYLDELA LEIGAKPDFC SLLFKDPKLA VRLYFGPCNS Y

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"The flavin-containing monooxygenase 2 gene (FMO2) of humans, but not of other primates, encodes a truncated, nonfunctional protein." Dolphin C.T., Beckett D.J., Janmohamed A., Cullingford T.E., Smith R.L., Shephard E.A., Phillips I.R. J. Biol. Chem. 273:30599-30607(1998) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, SUBCELLULAR LOCATION, TISSUE SPECIFICITY, ALLELE FMO2*1 TYR-471 INS. Tissue: Lung.
[2]	NIEHS SNPs program Submitted (JAN-2005) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA], ALLELE FMO2*1 TYR-471 INS, VARIANTS GLY-36; TYR-69; SER-81; SER-182; LEU-195; GLN-238; GLY-314; THR-391 AND LYS-413.
[3]	"Cloning of human full-length CDSs in BD Creator(TM) system donor vector." Kalnine N., Chen X., Rolfs A., Halleck A., Hines L., Eisenstein S., Koundinya M., Raphael J., Moreira D., Kelley T., LaBaer J., Lin Y., Phelan M., Farmer A. Submitted (MAY-2003) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
[4]	"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] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[5]	Mural R.J., Istrail S., Sutton G., Florea L., Halpern A.L., Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., Turner R. , Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W., Venter J.C. Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[6]	"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] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA], ALLELE FMO2*1 TYR-471 INS. Tissue: Skeletal muscle.
[7]	"Ethnic differences in human flavin-containing monooxygenase 2 (FMO2) polymorphisms: detection of expressed protein in African-Americans." Whetstine J.R., Yueh M.F., McCarver D.G., Williams D.E., Park C.S., Kang J.H., Cha Y.N., Dolphin C.T., Shephard E.A., Phillips I.R., Hines R.N. Toxicol. Appl. Pharmacol. 168:216-224(2000) [PubMed] [Europe PMC] [Abstract] Cited for: SUBCELLULAR LOCATION, TISSUE SPECIFICITY, ALLELE FMO2*1 TYR-471 INS.
[8]	"In vivo identification of sumoylation sites by a signature tag and cysteine-targeted affinity purification." Blomster H.A., Imanishi S.Y., Siimes J., Kastu J., Morrice N.A., Eriksson J.E., Sistonen L. J. Biol. Chem. 285:19324-19329(2010) [PubMed] [Europe PMC] [Abstract] Cited for: SUMOYLATION. Tissue: Cervix carcinoma.
[9]	"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] [Europe PMC] [Abstract] Cited for: VARIANTS GLY-36; ILE-59; SER-182; LEU-195; GLN-238; THR-391 AND LYS-413.
[10]	"The potentially deleterious functional variant flavin-containing monooxygenase 2*1 is at high frequency throughout sub-Saharan Africa." Veeramah K.R., Thomas M.G., Weale M.E., Zeitlyn D., Tarekegn A., Bekele E., Mendell N.R., Shephard E.A., Bradman N., Phillips I.R. Pharmacogenet. Genomics 18:877-886(2008) [PubMed] [Europe PMC] [Abstract] Cited for: ALLELE FMO2*1 TYR-471 INS.
+	Additional computationally mapped references.

Web resources

NIEHS-SNPs

Cross-references

Sequence databases
EMBL GenBank DDBJ	Y09267 mRNA. Translation: CAA70462.1. AY916056 Genomic DNA. Translation: AAW82431.1. BT006979 mRNA. Translation: AAP35625.1. AL021026 Genomic DNA. Translation: CAA15910.1. CH471067 Genomic DNA. Translation: EAW90889.1. BC005894 mRNA. Translation: AAH05894.1.
IPI	IPI00016005.
RefSeq	NP_001451.1. NM_001460.2.
UniGene	Hs.144912.
3D structure databases
ProteinModelPortal	Q99518.
SMR	Q99518. Positions 2-406.
ModBase	Search...
Protein-protein interaction databases
IntAct	Q99518. 2 interactions.
STRING	9606.ENSP00000209929.
PTM databases
PhosphoSite	Q99518.
Polymorphism databases
DMDM	6225373.
Proteomic databases
PaxDb	Q99518.
PRIDE	Q99518.
Protocols and materials databases
DNASU	2327.
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENST00000209929; ENSP00000209929; ENSG00000094963. ENST00000441535; ENSP00000405905; ENSG00000094963.
GeneID	2327.
KEGG	hsa:2327.
UCSC	uc001ghk.1. human.
Organism-specific databases
CTD	2327.
GeneCards	GC01P171154.
HGNC	HGNC:3770. FMO2.
HPA	HPA028261.
MIM	603955. gene.
neXtProt	NX_Q99518.
PharmGKB	PA164741534.
GenAtlas	Search...
Phylogenomic databases
eggNOG	COG2072.
HOGENOM	HOG000076537.
HOVERGEN	HBG002037.
InParanoid	Q99518.
KO	K00485.
OMA	PSERTMM.
OrthoDB	EOG48SGT0.
PhylomeDB	Q99518.
Enzyme and pathway databases
Reactome	REACT_111217. Metabolism.
Gene expression databases
ArrayExpress	Q99518.
Bgee	Q99518.
CleanEx	HS_FMO2.
Genevestigator	Q99518.
GermOnline	ENSG00000094963. Homo sapiens.
Family and domain databases
InterPro	IPR000960. Flavin_mOase. IPR020946. Flavin_mOase-like. IPR002254. Flavin_mOase_2. [Graphical view]
Pfam	PF00743. FMO-like. 1 hit. [Graphical view]
PRINTS	PR00370. FMOXYGENASE. PR01122. FMOXYGENASE2.
ProtoNet	Search...
Other
GenomeRNAi	2327.
NextBio	9443.
SOURCE	Search...

Entry information

Entry name

FMO2_HUMAN

Accession

Primary (citable) accession number: Q99518
Secondary accession number(s): Q5EBX4, Q86U73, Q9BRX1

Entry history

Integrated into UniProtKB/Swiss-Prot:	May 30, 2000
Last sequence update:	April 5, 2011
Last modified:	May 1, 2013
This is version 129 of the entry and version 4 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program

Disclaimer

Any medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.