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Protein

Dimethylaniline monooxygenase [N-oxide-forming] 2

Gene

FMO2

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

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.1 Publication

Catalytic activityi

N,N-dimethylaniline + NADPH + O2 = N,N-dimethylaniline N-oxide + NADP+ + H2O.

Cofactori

Protein has several cofactor binding sites:

Regions

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Nucleotide bindingi9 – 146FADSequence Analysis
Nucleotide bindingi191 – 1966NADPSequence Analysis

GO - Molecular functioni

GO - Biological processi

  • drug metabolic process Source: BHF-UCL
  • NADPH oxidation Source: UniProtKB
  • NADP metabolic process Source: BHF-UCL
  • organic acid metabolic process Source: BHF-UCL
  • small molecule metabolic process Source: Reactome
  • toxin metabolic process Source: BHF-UCL
  • xenobiotic metabolic process Source: BHF-UCL
Complete GO annotation...

Keywords - Molecular functioni

Monooxygenase, Oxidoreductase

Keywords - Ligandi

FAD, Flavoprotein, Magnesium, NADP

Enzyme and pathway databases

BRENDAi1.14.13.8. 2681.
ReactomeiREACT_13653. FMO oxidises nucleophiles.

Names & Taxonomyi

Protein namesi
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 namesi
Name:FMO2
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
ProteomesiUP000005640 Componenti: Chromosome 1

Organism-specific databases

HGNCiHGNC:3770. FMO2.

Subcellular locationi

GO - Cellular componenti

  • endoplasmic reticulum membrane Source: Reactome
  • integral component of membrane Source: UniProtKB-KW
  • membrane Source: UniProtKB
Complete GO annotation...

Keywords - Cellular componenti

Endoplasmic reticulum, Membrane, Microsome

Pathology & Biotechi

Organism-specific databases

PharmGKBiPA164741534.

Polymorphism and mutation databases

DMDMi327478599.

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Initiator methioninei1 – 11RemovedBy similarity
Chaini2 – 471470Dimethylaniline monooxygenase [N-oxide-forming] 2PRO_0000147646Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Modified residuei2 – 21N-acetylalanineBy similarity

Post-translational modificationi

The truncated form is probably unable to fold correctly and is rapidly degraded.
FMO2*1 is sumoylated at 'Lys-492'.1 Publication

Keywords - PTMi

Acetylation, Ubl conjugation

Proteomic databases

PaxDbiQ99518.
PRIDEiQ99518.

PTM databases

PhosphoSiteiQ99518.

Expressioni

Tissue specificityi

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.2 Publications

Gene expression databases

BgeeiQ99518.
CleanExiHS_FMO2.
GenevisibleiQ99518. HS.

Organism-specific databases

HPAiHPA028261.

Interactioni

Protein-protein interaction databases

IntActiQ99518. 2 interactions.
STRINGi9606.ENSP00000209929.

Structurei

3D structure databases

ProteinModelPortaliQ99518.
SMRiQ99518. Positions 3-406.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Sequence similaritiesi

Belongs to the FMO family.Curated

Keywords - Domaini

Transmembrane

Phylogenomic databases

eggNOGiCOG2072.
HOGENOMiHOG000076537.
HOVERGENiHBG002037.
InParanoidiQ99518.
OMAiFHTRFRS.
OrthoDBiEOG7GXPB6.
PhylomeDBiQ99518.
TreeFamiTF105285.

Family and domain databases

InterProiIPR012143. DiMe-aniline_mOase.
IPR000960. Flavin_mOase.
IPR020946. Flavin_mOase-like.
IPR002254. Flavin_mOase_2.
[Graphical view]
PfamiPF00743. FMO-like. 1 hit.
[Graphical view]
PIRSFiPIRSF000332. FMO. 1 hit.
PRINTSiPR00370. FMOXYGENASE.
PR01122. FMOXYGENASE2.

Sequencei

Sequence statusi: Complete.

Sequence processingi: The displayed sequence is further processed into a mature form.

Q99518-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MAKKVAVIGA GVSGLISLKC CVDEGLEPTC FERTEDIGGV WRFKENVEDG
60 70 80 90 100
RASIYQSVVT NTSKEMSCFS DFPMPEDFPN FLHNSKLLEY FRIFAKKFDL
110 120 130 140 150
LKYIQFQTTV LSVRKCPDFS SSGQWKVVTQ SNGKEQSAVF DAVMVCSGHH
160 170 180 190 200
ILPHIPLKSF PGMERFKGQY FHSRQYKHPD GFEGKRILVI GMGNSGSDIA
210 220 230 240 250
VELSKNAAQV FISTRHGTWV MSRISEDGYP WDSVFHTRFR SMLRNVLPRT
260 270 280 290 300
AVKWMIEQQM NRWFNHENYG LEPQNKYIMK EPVLNDDVPS RLLCGAIKVK
310 320 330 340 350
STVKELTETS AIFEDGTVEE NIDVIIFATG YSFSFPFLED SLVKVENNMV
360 370 380 390 400
SLYKYIFPAH LDKSTLACIG LIQPLGSIFP TAELQARWVT RVFKGLCSLP
410 420 430 440 450
SERTMMMDII KRNEKRIDLF GESQSQTLQT NYVDYLDELA LEIGAKPDFC
460 470
SLLFKDPKLA VRLYFGPCNS Y
Length:471
Mass (Da):53,644
Last modified:April 5, 2011 - v4
Checksum:iAF87E304131BA703
GO

Experimental Info

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Sequence conflicti71 – 711D → DD in AAW82431 (Ref. 2) Curated

Polymorphismi

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.

Natural variant

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Natural varianti36 – 361D → G.2 Publications
Corresponds to variant rs2020870 [ dbSNP | Ensembl ].
VAR_014840
Natural varianti59 – 591V → I.1 Publication
Corresponds to variant rs55708639 [ dbSNP | Ensembl ].
VAR_015361
Natural varianti69 – 691F → Y.1 Publication
Corresponds to variant rs28745274 [ dbSNP | Ensembl ].
VAR_022185
Natural varianti81 – 811F → S.1 Publication
Corresponds to variant rs2020860 [ dbSNP | Ensembl ].
VAR_014841
Natural varianti182 – 1821F → S.2 Publications
Corresponds to variant rs2307492 [ dbSNP | Ensembl ].
VAR_014842
Natural varianti195 – 1951S → L.2 Publications
Corresponds to variant rs2020862 [ dbSNP | Ensembl ].
VAR_014843
Natural varianti238 – 2381R → Q.2 Publications
Corresponds to variant rs28369895 [ dbSNP | Ensembl ].
VAR_015362
Natural varianti314 – 3141E → G.1 Publication
Corresponds to variant rs2020863 [ dbSNP | Ensembl ].
VAR_022186
Natural varianti391 – 3911R → T.2 Publications
Corresponds to variant rs28369899 [ dbSNP | Ensembl ].
VAR_015363
Natural varianti413 – 4131N → K.2 Publications
Corresponds to variant rs2020865 [ dbSNP | Ensembl ].
VAR_014844
Natural varianti471 – 4711Y → YQYRLVGPGQWEGARNAIFT QKQRILKPLKTRALKDSSNF SVSFLLKILGLLAVVVAFFC QLQWS in allele FMO2*1.
VAR_064887

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
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.
RefSeqiNP_001451.2. NM_001460.4.
UniGeneiHs.144912.

Genome annotation databases

EnsembliENST00000209929; ENSP00000209929; ENSG00000094963.
GeneIDi2327.
UCSCiuc001ghk.1. human.

Keywords - Coding sequence diversityi

Polymorphism

Cross-referencesi

Web resourcesi

NIEHS-SNPs

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
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.
RefSeqiNP_001451.2. NM_001460.4.
UniGeneiHs.144912.

3D structure databases

ProteinModelPortaliQ99518.
SMRiQ99518. Positions 3-406.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

IntActiQ99518. 2 interactions.
STRINGi9606.ENSP00000209929.

PTM databases

PhosphoSiteiQ99518.

Polymorphism and mutation databases

DMDMi327478599.

Proteomic databases

PaxDbiQ99518.
PRIDEiQ99518.

Protocols and materials databases

DNASUi2327.
Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000209929; ENSP00000209929; ENSG00000094963.
GeneIDi2327.
UCSCiuc001ghk.1. human.

Organism-specific databases

CTDi2327.
GeneCardsiGC01P171154.
HGNCiHGNC:3770. FMO2.
HPAiHPA028261.
MIMi603955. gene.
neXtProtiNX_Q99518.
PharmGKBiPA164741534.
GenAtlasiSearch...

Phylogenomic databases

eggNOGiCOG2072.
HOGENOMiHOG000076537.
HOVERGENiHBG002037.
InParanoidiQ99518.
OMAiFHTRFRS.
OrthoDBiEOG7GXPB6.
PhylomeDBiQ99518.
TreeFamiTF105285.

Enzyme and pathway databases

BRENDAi1.14.13.8. 2681.
ReactomeiREACT_13653. FMO oxidises nucleophiles.

Miscellaneous databases

ChiTaRSiFMO2. human.
GeneWikiiFMO2.
GenomeRNAii2327.
NextBioi9443.
PROiQ99518.
SOURCEiSearch...

Gene expression databases

BgeeiQ99518.
CleanExiHS_FMO2.
GenevisibleiQ99518. HS.

Family and domain databases

InterProiIPR012143. DiMe-aniline_mOase.
IPR000960. Flavin_mOase.
IPR020946. Flavin_mOase-like.
IPR002254. Flavin_mOase_2.
[Graphical view]
PfamiPF00743. FMO-like. 1 hit.
[Graphical view]
PIRSFiPIRSF000332. FMO. 1 hit.
PRINTSiPR00370. FMOXYGENASE.
PR01122. FMOXYGENASE2.
ProtoNetiSearch...

Publicationsi

« Hide 'large scale' publications
  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. 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.

Entry informationi

Entry nameiFMO2_HUMAN
AccessioniPrimary (citable) accession number: Q99518
Secondary accession number(s): Q5EBX4, Q86U73, Q9BRX1
Entry historyi
Integrated into UniProtKB/Swiss-Prot: May 30, 2000
Last sequence update: April 5, 2011
Last modified: July 22, 2015
This is version 150 of the entry and version 4 of the sequence. [Complete history]
Entry statusiReviewed (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.

Miscellaneousi

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. Human chromosome 1
    Human chromosome 1: entries, gene names and cross-references to MIM
  2. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  3. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  4. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  5. SIMILARITY comments
    Index of protein domains and families

External Data

Dasty 3

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into Uniref entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.