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Q99518 (FMO2_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified April 16, 2014. Version 137. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (5) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Sequence annotation·Sequences·References·Web links·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended 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
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length471 AA.
Sequence statusComplete.
Sequence processingThe displayed sequence is further processed into a mature form.
Protein existenceEvidence 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 componentEndoplasmic reticulum
Membrane
Microsome
   Coding sequence diversityPolymorphism
   DomainTransmembrane
   LigandFAD
Flavoprotein
Magnesium
NADP
   Molecular functionMonooxygenase
Oxidoreductase
   PTMAcetylation
Ubl conjugation
   Technical termComplete proteome
Reference proteome
Gene Ontology (GO)
   Biological_processNADP metabolic process

Inferred from direct assay PubMed 11744609. Source: BHF-UCL

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: Ensembl

small molecule metabolic process

Traceable author statement. Source: Reactome

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_componentendoplasmic reticulum membrane

Traceable author statement. Source: Reactome

integral component of membrane

Inferred from electronic annotation. Source: UniProtKB-KW

membrane

Inferred from direct assay Ref.1. Source: UniProtKB

   Molecular_functionN,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

monooxygenase activity

Traceable author statement. Source: Reactome

Complete GO annotation...

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Initiator methionine11Removed By similarity
Chain2 – 471470Dimethylaniline monooxygenase [N-oxide-forming] 2
PRO_0000147646

Regions

Nucleotide binding9 – 146FAD Potential
Nucleotide binding191 – 1966NADP Potential

Amino acid modifications

Modified residue21N-acetylalanine By similarity

Natural variations

Natural variant361D → G. Ref.2 Ref.9
Corresponds to variant rs2020870 [ dbSNP | Ensembl ].
VAR_014840
Natural variant591V → I. Ref.9
Corresponds to variant rs55708639 [ dbSNP | Ensembl ].
VAR_015361
Natural variant691F → Y. Ref.2
Corresponds to variant rs28745274 [ dbSNP | Ensembl ].
VAR_022185
Natural variant811F → S. Ref.2
Corresponds to variant rs2020860 [ dbSNP | Ensembl ].
VAR_014841
Natural variant1821F → S. Ref.2 Ref.9
Corresponds to variant rs2307492 [ dbSNP | Ensembl ].
VAR_014842
Natural variant1951S → L. Ref.2 Ref.9
Corresponds to variant rs2020862 [ dbSNP | Ensembl ].
VAR_014843
Natural variant2381R → Q. Ref.2 Ref.9
Corresponds to variant rs28369895 [ dbSNP | Ensembl ].
VAR_015362
Natural variant3141E → G. Ref.2
Corresponds to variant rs2020863 [ dbSNP | Ensembl ].
VAR_022186
Natural variant3911R → T. Ref.2 Ref.9
Corresponds to variant rs28369899 [ dbSNP | Ensembl ].
VAR_015363
Natural variant4131N → K. Ref.2 Ref.9
Corresponds to variant rs2020865 [ dbSNP | Ensembl ].
VAR_014844
Natural variant4711Y → YQYRLVGPGQWEGARNAIFT QKQRILKPLKTRALKDSSNF SVSFLLKILGLLAVVVAFFC QLQWS in allele FMO2*1.
VAR_064887

Experimental info

Sequence conflict711D → DD in AAW82431. Ref.2

Sequences

Sequence LengthMass (Da)Tools
Q99518 [UniParc].

Last modified April 5, 2011. Version 4.
Checksum: AF87E304131BA703

FASTA47153,644
        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 

« Hide

References

« Hide '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. expand/collapse author list , 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. expand/collapse author list , 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

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.
RefSeqNP_001451.1. NM_001460.3.
UniGeneHs.144912.

3D structure databases

ProteinModelPortalQ99518.
SMRQ99518. Positions 1-446.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

IntActQ99518. 2 interactions.
STRING9606.ENSP00000209929.

PTM databases

PhosphoSiteQ99518.

Polymorphism databases

DMDM327478599.

Proteomic databases

PaxDbQ99518.
PRIDEQ99518.

Protocols and materials databases

DNASU2327.
StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000209929; ENSP00000209929; ENSG00000094963.
ENST00000441535; ENSP00000405905; ENSG00000094963.
GeneID2327.
KEGGhsa:2327.
UCSCuc001ghk.1. human.

Organism-specific databases

CTD2327.
GeneCardsGC01P171154.
HGNCHGNC:3770. FMO2.
HPAHPA028261.
MIM603955. gene.
neXtProtNX_Q99518.
PharmGKBPA164741534.
GenAtlasSearch...

Phylogenomic databases

eggNOGCOG2072.
HOGENOMHOG000076537.
HOVERGENHBG002037.
InParanoidQ99518.
KOK00485.
OMAFHTRFRS.
OrthoDBEOG7GXPB6.
PhylomeDBQ99518.
TreeFamTF105285.

Enzyme and pathway databases

ReactomeREACT_111217. Metabolism.

Gene expression databases

ArrayExpressQ99518.
BgeeQ99518.
CleanExHS_FMO2.
GenevestigatorQ99518.

Family and domain databases

InterProIPR000960. Flavin_mOase.
IPR020946. Flavin_mOase-like.
IPR002254. Flavin_mOase_2.
[Graphical view]
PfamPF00743. FMO-like. 1 hit.
[Graphical view]
PRINTSPR00370. FMOXYGENASE.
PR01122. FMOXYGENASE2.
ProtoNetSearch...

Other

GeneWikiFMO2.
GenomeRNAi2327.
NextBio9443.
PROQ99518.
SOURCESearch...

Entry information

Entry nameFMO2_HUMAN
AccessionPrimary (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: April 16, 2014
This is version 137 of the entry and version 4 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny 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.

Relevant documents

SIMILARITY comments

Index of protein domains and families

MIM cross-references

Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

Human polymorphisms and disease mutations

Index of human polymorphisms and disease mutations

Human entries with polymorphisms or disease mutations

List of human entries with polymorphisms or disease mutations

Human chromosome 1

Human chromosome 1: entries, gene names and cross-references to MIM