FMO2_MOUSE
ID FMO2_MOUSE Reviewed; 535 AA.
AC Q8K2I3; Q9QZF7;
DT 25-OCT-2005, integrated into UniProtKB/Swiss-Prot.
DT 23-JAN-2007, sequence version 3.
DT 03-AUG-2022, entry version 155.
DE RecName: Full=Dimethylaniline monooxygenase [N-oxide-forming] 2 {ECO:0000305};
DE EC=1.14.13.- {ECO:0000269|PubMed:18930751};
DE AltName: Full=Dimethylaniline oxidase 2;
DE AltName: Full=Pulmonary flavin-containing monooxygenase 2;
DE Short=FMO 2;
GN Name=Fmo2 {ECO:0000312|MGI:MGI:1916776};
OS Mus musculus (Mouse).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Mus; Mus.
OX NCBI_TaxID=10090;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA], AND CHARACTERIZATION.
RC STRAIN=C57BL/6J; TISSUE=Kidney;
RX PubMed=11835629; DOI=10.1002/jbt.10009;
RA Karoly E.D., Rose R.L.;
RT "Sequencing, expression, and characterization of cDNA expressed flavin-
RT containing monooxygenase 2 from mouse.";
RL J. Biochem. Mol. Toxicol. 15:300-308(2001).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=Czech II; TISSUE=Mammary tumor;
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 project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [3]
RP FUNCTION, AND BIOPHYSICOCHEMICAL PROPERTIES.
RX PubMed=18930751; DOI=10.1016/j.taap.2008.09.017;
RA Henderson M.C., Siddens L.K., Morre J.T., Krueger S.K., Williams D.E.;
RT "Metabolism of the anti-tuberculosis drug ethionamide by mouse and human
RT FMO1, FMO2 and FMO3 and mouse and human lung microsomes.";
RL Toxicol. Appl. Pharmacol. 233:420-427(2008).
RN [4]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Heart, Kidney, Lung, and Pancreas;
RX PubMed=21183079; DOI=10.1016/j.cell.2010.12.001;
RA Huttlin E.L., Jedrychowski M.P., Elias J.E., Goswami T., Rad R.,
RA Beausoleil S.A., Villen J., Haas W., Sowa M.E., Gygi S.P.;
RT "A tissue-specific atlas of mouse protein phosphorylation and expression.";
RL Cell 143:1174-1189(2010).
CC -!- FUNCTION: Catalyzes the oxidative metabolism of numerous xenobiotics,
CC including mainly therapeutic drugs and insecticides that contain a soft
CC nucleophile, most commonly nitrogen and sulfur and participates to
CC their bioactivation (PubMed:18930751). Catalyzes the S-oxygenation of
CC the prodrug ethionamide (ETA) to the S-oxide (ETASO), the first step in
CC its bioactivation following by the second oxygenation to the sulfinic
CC acid but to a lesser extend (PubMed:18930751).
CC {ECO:0000269|PubMed:18930751}.
CC -!- COFACTOR:
CC Name=FAD; Xref=ChEBI:CHEBI:57692; Evidence={ECO:0000250};
CC -!- COFACTOR:
CC Name=Mg(2+); Xref=ChEBI:CHEBI:18420; Evidence={ECO:0000250};
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC Kinetic parameters:
CC KM=2131 uM for ethionamide {ECO:0000269|PubMed:18930751};
CC pH dependence:
CC Optimum pH is 10.5.;
CC -!- SUBCELLULAR LOCATION: Microsome membrane
CC {ECO:0000250|UniProtKB:P17635}; Single-pass membrane protein
CC {ECO:0000250|UniProtKB:P17635}. Endoplasmic reticulum membrane
CC {ECO:0000250|UniProtKB:P17635}; Single-pass membrane protein
CC {ECO:0000250|UniProtKB:P17635}.
CC -!- SIMILARITY: Belongs to the FMO family. {ECO:0000305}.
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DR EMBL; AF184981; AAD56413.1; -; mRNA.
DR EMBL; BC031415; AAH31415.1; -; mRNA.
DR CCDS; CCDS15425.1; -.
DR RefSeq; NP_061369.2; NM_018881.3.
DR RefSeq; XP_006497012.1; XM_006496949.3.
DR AlphaFoldDB; Q8K2I3; -.
DR SMR; Q8K2I3; -.
DR BioGRID; 207761; 5.
DR STRING; 10090.ENSMUSP00000044405; -.
DR iPTMnet; Q8K2I3; -.
DR PhosphoSitePlus; Q8K2I3; -.
DR jPOST; Q8K2I3; -.
DR MaxQB; Q8K2I3; -.
DR PaxDb; Q8K2I3; -.
DR PeptideAtlas; Q8K2I3; -.
DR PRIDE; Q8K2I3; -.
DR ProteomicsDB; 267373; -.
DR Antibodypedia; 34377; 149 antibodies from 25 providers.
DR DNASU; 55990; -.
DR Ensembl; ENSMUST00000045902; ENSMUSP00000044405; ENSMUSG00000040170.
DR Ensembl; ENSMUST00000111510; ENSMUSP00000107135; ENSMUSG00000040170.
DR GeneID; 55990; -.
DR KEGG; mmu:55990; -.
DR UCSC; uc007dgz.1; mouse.
DR CTD; 2327; -.
DR MGI; MGI:1916776; Fmo2.
DR VEuPathDB; HostDB:ENSMUSG00000040170; -.
DR eggNOG; KOG1399; Eukaryota.
DR GeneTree; ENSGT00940000161099; -.
DR HOGENOM; CLU_006909_8_2_1; -.
DR InParanoid; Q8K2I3; -.
DR OMA; DCYERET; -.
DR OrthoDB; 405736at2759; -.
DR PhylomeDB; Q8K2I3; -.
DR TreeFam; TF105285; -.
DR BRENDA; 1.14.13.8; 3474.
DR Reactome; R-MMU-217271; FMO oxidises nucleophiles.
DR BioGRID-ORCS; 55990; 1 hit in 73 CRISPR screens.
DR ChiTaRS; Fmo2; mouse.
DR PRO; PR:Q8K2I3; -.
DR Proteomes; UP000000589; Chromosome 1.
DR RNAct; Q8K2I3; protein.
DR Bgee; ENSMUSG00000040170; Expressed in lumbar dorsal root ganglion and 184 other tissues.
DR ExpressionAtlas; Q8K2I3; baseline and differential.
DR Genevisible; Q8K2I3; MM.
DR GO; GO:0005789; C:endoplasmic reticulum membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0016021; C:integral component of membrane; IEA:UniProtKB-KW.
DR GO; GO:0016020; C:membrane; ISS:UniProtKB.
DR GO; GO:0050660; F:flavin adenine dinucleotide binding; IEA:InterPro.
DR GO; GO:0004497; F:monooxygenase activity; IDA:MGI.
DR GO; GO:0004499; F:N,N-dimethylaniline monooxygenase activity; ISO:MGI.
DR GO; GO:0050661; F:NADP binding; IEA:InterPro.
DR GO; GO:0097009; P:energy homeostasis; IGI:MGI.
DR GO; GO:0006739; P:NADP metabolic process; ISO:MGI.
DR GO; GO:0070995; P:NADPH oxidation; ISS:UniProtKB.
DR GO; GO:0046322; P:negative regulation of fatty acid oxidation; IGI:MGI.
DR GO; GO:0006082; P:organic acid metabolic process; ISO:MGI.
DR GO; GO:0072592; P:oxygen metabolic process; IDA:MGI.
DR GO; GO:0009404; P:toxin metabolic process; ISO:MGI.
DR GO; GO:0006805; P:xenobiotic metabolic process; ISO:MGI.
DR Gene3D; 3.50.50.60; -; 2.
DR InterPro; IPR036188; FAD/NAD-bd_sf.
DR InterPro; IPR000960; Flavin_mOase.
DR InterPro; IPR020946; Flavin_mOase-like.
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 SUPFAM; SSF51905; SSF51905; 2.
PE 1: Evidence at protein level;
KW Acetylation; Endoplasmic reticulum; FAD; Flavoprotein; Isopeptide bond;
KW Magnesium; Membrane; Microsome; Monooxygenase; NADP; Oxidoreductase;
KW Reference proteome; Transmembrane; Transmembrane helix; Ubl conjugation.
FT INIT_MET 1
FT /note="Removed"
FT /evidence="ECO:0000250|UniProtKB:P17635"
FT CHAIN 2..535
FT /note="Dimethylaniline monooxygenase [N-oxide-forming] 2"
FT /id="PRO_0000147648"
FT TRANSMEM 510..530
FT /note="Helical"
FT /evidence="ECO:0000255"
FT BINDING 9..13
FT /ligand="FAD"
FT /ligand_id="ChEBI:CHEBI:57692"
FT /evidence="ECO:0000250|UniProtKB:Q9HFE4"
FT BINDING 32
FT /ligand="FAD"
FT /ligand_id="ChEBI:CHEBI:57692"
FT /evidence="ECO:0000250|UniProtKB:Q9HFE4"
FT BINDING 40..41
FT /ligand="FAD"
FT /ligand_id="ChEBI:CHEBI:57692"
FT /evidence="ECO:0000250|UniProtKB:Q9HFE4"
FT BINDING 60..61
FT /ligand="NADP(+)"
FT /ligand_id="ChEBI:CHEBI:58349"
FT /evidence="ECO:0000250|UniProtKB:Q9HFE4"
FT BINDING 61..62
FT /ligand="FAD"
FT /ligand_id="ChEBI:CHEBI:57692"
FT /evidence="ECO:0000250|UniProtKB:Q9HFE4"
FT BINDING 195..198
FT /ligand="NADP(+)"
FT /ligand_id="ChEBI:CHEBI:58349"
FT /evidence="ECO:0000250|UniProtKB:Q9HFE4"
FT MOD_RES 2
FT /note="N-acetylalanine"
FT /evidence="ECO:0000250|UniProtKB:P17635"
FT CROSSLNK 492
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO)"
FT /evidence="ECO:0000250|UniProtKB:Q99518"
FT CONFLICT 169
FT /note="Q -> R (in Ref. 1; AAD56413)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 535 AA; 60974 MW; 705FAD9D8EADB1B1 CRC64;
MAKKVVVIGA GVSGLISLKC CVDEGLEPTC FERTEDIGGL WRFKENVEDG RASIYRSVIT
NTSKEMSCFS DFPMPEDFPN FLHNSKLLEY FRIFAKKFDL LKYIQFQTTV ISVKKRPDFA
SSGQWEVYTQ SNGKEQRTVF DAVMVCSGHH IQPHLPLKSF PGIERFRGQY FHSREYKHPV
GFEGKRILVV GIGNSAADIA SELSKTAAQV FVSTRHGSWV MSRISEDGYP WDMVFHTRFS
SMLRNVLPRT VVKWMMEQQM NRWFNHENYG LVPQNKYLMK EPVLNDDLPS RLLYGAIKVK
TRVKELTETA VVFEDGTVEE DVDIIVFATG YTFSFSFLED SLVKVEDNRV SLYKAMFPPH
LEKPTLACIG LIQPLGSIFP TVELQARWAT RVFKGLCSLP SETTMMADIV ERNEKRVNLF
GKSQSQILQT NYVDYLDELA LEIGAKPDFV SLFFKDPKLA VKLYFGPCNS YQYRLVGPGQ
WEGARNAILT QKQRILKPLK TRTLQSSDSA PVSFLLKILG LLAVVLAFFF QLQGF