ID   FMO2_HUMAN              Reviewed;         535 AA.
AC   Q99518; Q5EBX4; Q9BRX1;
DT   30-MAY-2000, integrated into UniProtKB/Swiss-Prot.
DT   23-JAN-2007, sequence version 3.
DT   07-JUL-2009, entry version 92.
DE   RecName: Full=Dimethylaniline monooxygenase [N-oxide-forming] 2;
DE            EC=1.14.13.8;
DE   AltName: Full=Pulmonary flavin-containing monooxygenase 2;
DE            Short=FMO 2;
DE   AltName: Full=FMO 1B1;
DE   AltName: Full=Dimethylaniline oxidase 2;
GN   Name=FMO2;
OS   Homo sapiens (Human).
OC   Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
OC   Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini;
OC   Catarrhini; Hominidae; Homo.
OX   NCBI_TaxID=9606;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [MRNA].
RC   TISSUE=Lung;
RX   MEDLINE=99023992; PubMed=9804831; DOI=10.1074/jbc.273.46.30599;
RA   Dolphin C.T., Beckett D.J., Janmohamed A., Cullingford T.E.,
RA   Smith R.L., Shephard E.A., Phillips I.R.;
RT   "The flavin-containing monooxygenase 2 gene (FMO2) of humans, but not
RT   of other primates, encodes a truncated, nonfunctional protein.";
RL   J. Biol. Chem. 273:30599-30607(1998).
RN   [2]
RP   NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND VARIANTS GLY-36; TYR-69;
RP   SER-81; SER-182; LEU-195; GLN-238; GLY-314; THR-391 AND LYS-413.
RG   NIEHS SNPs program;
RL   Submitted (JAN-2005) to the EMBL/GenBank/DDBJ databases.
RN   [3]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX   PubMed=16710414; DOI=10.1038/nature04727;
RA   Gregory S.G., Barlow K.F., McLay K.E., Kaul R., Swarbreck D.,
RA   Dunham A., Scott C.E., Howe K.L., Woodfine K., Spencer C.C.A.,
RA   Jones M.C., Gillson C., Searle S., Zhou Y., Kokocinski F.,
RA   McDonald L., Evans R., Phillips K., Atkinson A., Cooper R., Jones C.,
RA   Hall R.E., Andrews T.D., Lloyd C., Ainscough R., Almeida J.P.,
RA   Ambrose K.D., Anderson F., Andrew R.W., Ashwell R.I.S., Aubin K.,
RA   Babbage A.K., Bagguley C.L., Bailey J., Beasley H., Bethel G.,
RA   Bird C.P., Bray-Allen S., Brown J.Y., Brown A.J., Buckley D.,
RA   Burton J., Bye J., Carder C., Chapman J.C., Clark S.Y., Clarke G.,
RA   Clee C., Cobley V., Collier R.E., Corby N., Coville G.J., Davies J.,
RA   Deadman R., Dunn M., Earthrowl M., Ellington A.G., Errington H.,
RA   Frankish A., Frankland J., French L., Garner P., Garnett J., Gay L.,
RA   Ghori M.R.J., Gibson R., Gilby L.M., Gillett W., Glithero R.J.,
RA   Grafham D.V., Griffiths C., Griffiths-Jones S., Grocock R.,
RA   Hammond S., Harrison E.S.I., Hart E., Haugen E., Heath P.D.,
RA   Holmes S., Holt K., Howden P.J., Hunt A.R., Hunt S.E., Hunter G.,
RA   Isherwood J., James R., Johnson C., Johnson D., Joy A., Kay M.,
RA   Kershaw J.K., Kibukawa M., Kimberley A.M., King A., Knights A.J.,
RA   Lad H., Laird G., Lawlor S., Leongamornlert D.A., Lloyd D.M.,
RA   Loveland J., Lovell J., Lush M.J., Lyne R., Martin S.,
RA   Mashreghi-Mohammadi M., Matthews L., Matthews N.S.W., McLaren S.,
RA   Milne S., Mistry S., Moore M.J.F., Nickerson T., O'Dell C.N.,
RA   Oliver K., Palmeiri A., Palmer S.A., Parker A., Patel D., Pearce A.V.,
RA   Peck A.I., Pelan S., Phelps K., Phillimore B.J., Plumb R., Rajan J.,
RA   Raymond C., Rouse G., Saenphimmachak C., Sehra H.K., Sheridan E.,
RA   Shownkeen R., Sims S., Skuce C.D., Smith M., Steward C.,
RA   Subramanian S., Sycamore N., Tracey A., Tromans A., Van Helmond Z.,
RA   Wall M., Wallis J.M., White S., Whitehead S.L., Wilkinson J.E.,
RA   Willey D.L., Williams H., Wilming L., Wray P.W., Wu Z., Coulson A.,
RA   Vaudin M., Sulston J.E., Durbin R.M., Hubbard T., Wooster R.,
RA   Dunham I., Carter N.P., McVean G., Ross M.T., Harrow J., Olson M.V.,
RA   Beck S., Rogers J., Bentley D.R.;
RT   "The DNA sequence and biological annotation of human chromosome 1.";
RL   Nature 441:315-321(2006).
RN   [4]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC   TISSUE=Skeletal muscle;
RX   PubMed=15489334; DOI=10.1101/gr.2596504;
RG   The MGC Project Team;
RT   "The status, quality, and expansion of the NIH full-length cDNA
RT   project: the Mammalian Gene Collection (MGC).";
RL   Genome Res. 14:2121-2127(2004).
RN   [5]
RP   VARIANTS GLY-36; ILE-59; SER-182; LEU-195; GLN-238; THR-391 AND
RP   LYS-413.
RX   MEDLINE=22414999; PubMed=12527699; DOI=10.1124/dmd.31.2.187;
RA   Furnes B., Feng J., Sommer S.S., Schlenk D.;
RT   "Identification of novel variants of the flavin-containing
RT   monooxygenase gene family in African Americans.";
RL   Drug Metab. Dispos. 31:187-193(2003).
CC   -!- FUNCTION: Catalyzes the N-oxidation of certain primary alkylamines
CC       to their oximes via an N-hydroxylamine intermediate. Inactive
CC       toward certain tertiary amines, such as imipramine or
CC       chloropromazine. Can catalyze the S-oxidation of methimazole. The
CC       truncated form is catalytically inactive.
CC   -!- CATALYTIC ACTIVITY: N,N-dimethylaniline + NADPH + O(2) = N,N-
CC       dimethylaniline N-oxide + NADP(+) + H(2)O.
CC   -!- COFACTOR: FAD.
CC   -!- COFACTOR: Magnesium.
CC   -!- SUBCELLULAR LOCATION: Microsome membrane. Endoplasmic reticulum
CC       membrane.
CC   -!- TISSUE SPECIFICITY: Expressed predominantly in lung, and at a much
CC       lesser extent in kidney.
CC   -!- PTM: The truncated form is probably unable to fold correctly and
CC       is rapidly degraded.
CC   -!- POLYMORPHISM: There are two alleles; one major, FMO2X472,
CC       (truncated form) and one minor, FMO2Q472, (shown here) (full-
CC       length form similar to the protein found in other mammals). A
CC       nonsense mutation transforms the Gln-472 in a premature stop
CC       codon. The truncated protein is catalytically inactive. The minor
CC       allele is present at a frequency of approximately 4% in the sample
CC       of population of African descent.
CC   -!- SIMILARITY: Belongs to the FMO family.
CC   -!- WEB RESOURCE: Name=NIEHS-SNPs;
CC       URL="http://egp.gs.washington.edu/data/fmo2/";
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DR   EMBL; Y09267; CAA70462.1; ALT_TERM; mRNA.
DR   EMBL; AY916056; AAW82431.1; ALT_TERM; Genomic_DNA.
DR   EMBL; AL021026; CAA15910.1; ALT_TERM; Genomic_DNA.
DR   EMBL; BC005894; AAH05894.1; ALT_TERM; mRNA.
DR   IPI; IPI00016005; -.
DR   RefSeq; NP_001451.1; -.
DR   UniGene; Hs.144912; -.
DR   PRIDE; Q99518; -.
DR   Ensembl; ENSG00000094963; Homo sapiens.
DR   GeneID; 2327; -.
DR   KEGG; hsa:2327; -.
DR   GeneCards; GC01P169420; -.
DR   HGNC; HGNC:3770; FMO2.
DR   MIM; 603955; gene.
DR   PharmGKB; PA28187; -.
DR   HOGENOM; Q99518; -.
DR   HOVERGEN; Q99518; -.
DR   BRENDA; 1.14.13.8; 247.
DR   Reactome; REACT_13433; Biological oxidations.
DR   NextBio; 9443; -.
DR   ArrayExpress; Q99518; -.
DR   Bgee; Q99518; -.
DR   CleanEx; HS_FMO2; -.
DR   GermOnline; ENSG00000094963; Homo sapiens.
DR   GO; GO:0016021; C:integral to membrane; IEA:UniProtKB-KW.
DR   GO; GO:0031227; C:intrinsic to endoplasmic reticulum membrane; IEA:InterPro.
DR   GO; GO:0005792; C:microsome; IEA:UniProtKB-SubCell.
DR   GO; GO:0050660; F:FAD binding; IEA:InterPro.
DR   GO; GO:0004499; F:flavin-containing monooxygenase activity; IEA:EC.
DR   GO; GO:0000287; F:magnesium ion binding; IEA:UniProtKB-KW.
DR   GO; GO:0050661; F:NADP or NADPH binding; IEA:InterPro.
DR   GO; GO:0055114; P:oxidation reduction; IEA:UniProtKB-KW.
DR   InterPro; IPR012143; dManiline_mOase.
DR   InterPro; IPR000960; Flavin_mOase.
DR   InterPro; IPR002254; Flavin_mOase_2.
DR   Pfam; PF00743; FMO-like; 1.
DR   PIRSF; PIRSF000332; FMO; 1.
DR   PRINTS; PR00370; FMOXYGENASE.
DR   PRINTS; PR01122; FMOXYGENASE2.
DR   ProDom; PD000139; FAD_pyr_redox; 1.
PE   2: Evidence at transcript level;
KW   Acetylation; Complete proteome; Endoplasmic reticulum; FAD;
KW   Flavoprotein; Magnesium; Membrane; Microsome; Monooxygenase; NADP;
KW   Oxidoreductase; Polymorphism; Transmembrane.
FT   INIT_MET      1      1       Removed (By similarity).
FT   CHAIN         2    535       Dimethylaniline monooxygenase [N-oxide-
FT                                forming] 2.
FT                                /FTId=PRO_0000147646.
FT   NP_BIND       9     14       FAD (Potential).
FT   NP_BIND     191    196       NADP (Potential).
FT   MOD_RES       2      2       N-acetylalanine (By similarity).
FT   VARIANT      36     36       D -> G (in dbSNP:rs2020870).
FT                                /FTId=VAR_014840.
FT   VARIANT      59     59       V -> I.
FT                                /FTId=VAR_015361.
FT   VARIANT      69     69       F -> Y (in dbSNP:rs28745274).
FT                                /FTId=VAR_022185.
FT   VARIANT      81     81       F -> S (in dbSNP:rs2020860).
FT                                /FTId=VAR_014841.
FT   VARIANT     182    182       F -> S (in dbSNP:rs2307492).
FT                                /FTId=VAR_014842.
FT   VARIANT     195    195       S -> L (in dbSNP:rs2020862).
FT                                /FTId=VAR_014843.
FT   VARIANT     238    238       R -> Q (in dbSNP:rs28369895).
FT                                /FTId=VAR_015362.
FT   VARIANT     314    314       E -> G (in dbSNP:rs2020863).
FT                                /FTId=VAR_022186.
FT   VARIANT     391    391       R -> T (in dbSNP:rs28369899).
FT                                /FTId=VAR_015363.
FT   VARIANT     413    413       N -> K (in dbSNP:rs2020865).
FT                                /FTId=VAR_014844.
FT   CONFLICT     71     71       D -> DD (in Ref. 2; AAW82431).
SQ   SEQUENCE   535 AA;  60907 MW;  39A5587AC7BF50B8 CRC64;
     MAKKVAVIGA GVSGLISLKC CVDEGLEPTC FERTEDIGGV WRFKENVEDG RASIYQSVVT
     NTSKEMSCFS DFPMPEDFPN FLHNSKLLEY FRIFAKKFDL LKYIQFQTTV LSVRKCPDFS
     SSGQWKVVTQ SNGKEQSAVF DAVMVCSGHH ILPHIPLKSF PGMERFKGQY FHSRQYKHPD
     GFEGKRILVI GMGNSGSDIA VELSKNAAQV FISTRHGTWV MSRISEDGYP WDSVFHTRFR
     SMLRNVLPRT AVKWMIEQQM NRWFNHENYG LEPQNKYIMK EPVLNDDVPS RLLCGAIKVK
     STVKELTETS AIFEDGTVEE NIDVIIFATG YSFSFPFLED SLVKVENNMV SLYKYIFPAH
     LDKSTLACIG LIQPLGSIFP TAELQARWVT RVFKGLCSLP SERTMMMDII KRNEKRIDLF
     GESQSQTLQT NYVDYLDELA LEIGAKPDFC SLLFKDPKLA VRLYFGPCNS YQYRLVGPGQ
     WEGARNAIFT QKQRILKPLK TRALKDSSNF SVSFLLKILG LLAVVVAFFC QLQWS
//