ID COMT_MOUSE Reviewed; 265 AA. AC O88587; Q91XH4; DT 15-DEC-1998, integrated into UniProtKB/Swiss-Prot. DT 03-OCT-2012, sequence version 2. DT 27-MAR-2024, entry version 189. DE RecName: Full=Catechol O-methyltransferase {ECO:0000305}; DE EC=2.1.1.6 {ECO:0000250|UniProtKB:P21964}; GN Name=Comt {ECO:0000312|MGI:MGI:88470}; Synonyms=Comt1; 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]. RX PubMed=9707588; DOI=10.1073/pnas.95.17.9991; RA Gogos J.A., Morgan M., Luine V., Santha M., Ogawa S., Pfaff D., RA Karayiorgou M.; RT "Catechol-O-methyltransferase-deficient mice exhibit sexually dimorphic RT changes in catecholamine levels and behavior."; RL Proc. Natl. Acad. Sci. U.S.A. 95:9991-9996(1998). RN [2] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. RC STRAIN=C57BL/6J; RX PubMed=16141072; DOI=10.1126/science.1112014; RA Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N., RA Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K., RA Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J., RA Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R., RA Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T., RA Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A., RA Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B., RA Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M., RA Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S., RA Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E., RA Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D., RA Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M., RA Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H., RA Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V., RA Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S., RA Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H., RA Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N., RA Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F., RA Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G., RA Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z., RA Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C., RA Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y., RA Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S., RA Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K., RA Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R., RA van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H., RA Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M., RA Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C., RA Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S., RA Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K., RA Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M., RA Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C., RA Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A., RA Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y.; RT "The transcriptional landscape of the mammalian genome."; RL Science 309:1559-1563(2005). RN [3] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RC STRAIN=C57BL/6J; RX PubMed=19468303; DOI=10.1371/journal.pbio.1000112; RA Church D.M., Goodstadt L., Hillier L.W., Zody M.C., Goldstein S., She X., RA Bult C.J., Agarwala R., Cherry J.L., DiCuccio M., Hlavina W., Kapustin Y., RA Meric P., Maglott D., Birtle Z., Marques A.C., Graves T., Zhou S., RA Teague B., Potamousis K., Churas C., Place M., Herschleb J., Runnheim R., RA Forrest D., Amos-Landgraf J., Schwartz D.C., Cheng Z., Lindblad-Toh K., RA Eichler E.E., Ponting C.P.; RT "Lineage-specific biology revealed by a finished genome assembly of the RT mouse."; RL PLoS Biol. 7:E1000112-E1000112(2009). RN [4] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. RC STRAIN=FVB/N; TISSUE=Liver; 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 [5] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-261, AND IDENTIFICATION BY RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Liver; RX PubMed=17242355; DOI=10.1073/pnas.0609836104; RA Villen J., Beausoleil S.A., Gerber S.A., Gygi S.P.; RT "Large-scale phosphorylation analysis of mouse liver."; RL Proc. Natl. Acad. Sci. U.S.A. 104:1488-1493(2007). RN [6] RP MUTAGENESIS OF ARG-51, AND FUNCTION. RX PubMed=18794526; DOI=10.1073/pnas.0807219105; RA Du X., Schwander M., Moresco E.M.Y., Viviani P., Haller C., RA Hildebrand M.S., Pak K., Tarantino L., Roberts A., Richardson H., Koob G., RA Najmabadi H., Ryan A.F., Smith R.J.H., Mueller U., Beutler B.; RT "A catechol-O-methyltransferase that is essential for auditory function in RT mice and humans."; RL Proc. Natl. Acad. Sci. U.S.A. 105:14609-14614(2008). RN [7] RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RX PubMed=19144319; DOI=10.1016/j.immuni.2008.11.006; RA Trost M., English L., Lemieux S., Courcelles M., Desjardins M., RA Thibault P.; RT "The phagosomal proteome in interferon-gamma-activated macrophages."; RL Immunity 30:143-154(2009). RN [8] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-261, AND IDENTIFICATION BY RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Embryonic fibroblast; RX PubMed=19131326; DOI=10.1074/mcp.m800451-mcp200; RA Sweet S.M., Bailey C.M., Cunningham D.L., Heath J.K., Cooper H.J.; RT "Large scale localization of protein phosphorylation by use of electron RT capture dissociation mass spectrometry."; RL Mol. Cell. Proteomics 8:904-912(2009). RN [9] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-261, AND IDENTIFICATION BY RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Brain, Brown adipose tissue, Heart, Kidney, Liver, Lung, RC Pancreas, Spleen, and Testis; 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 O-methylation, and thereby the inactivation, of CC catecholamine neurotransmitters and catechol hormones. Also shortens CC the biological half-lives of certain neuroactive drugs, like L-DOPA, CC alpha-methyl DOPA and isoproterenol. {ECO:0000269|PubMed:18794526}. CC -!- CATALYTIC ACTIVITY: CC Reaction=a catechol + S-adenosyl-L-methionine = a guaiacol + H(+) + S- CC adenosyl-L-homocysteine; Xref=Rhea:RHEA:17877, ChEBI:CHEBI:15378, CC ChEBI:CHEBI:33566, ChEBI:CHEBI:57856, ChEBI:CHEBI:59789, CC ChEBI:CHEBI:134251; EC=2.1.1.6; CC Evidence={ECO:0000250|UniProtKB:P21964}; CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:17878; CC Evidence={ECO:0000250|UniProtKB:P21964}; CC -!- CATALYTIC ACTIVITY: CC Reaction=2-hydroxyestrone + S-adenosyl-L-methionine = 2-hydroxy-3- CC methoxy-estrone + H(+) + S-adenosyl-L-homocysteine; CC Xref=Rhea:RHEA:53108, ChEBI:CHEBI:1156, ChEBI:CHEBI:15378, CC ChEBI:CHEBI:57856, ChEBI:CHEBI:59789, ChEBI:CHEBI:136980; CC Evidence={ECO:0000250|UniProtKB:P21964}; CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:53109; CC Evidence={ECO:0000250|UniProtKB:P21964}; CC -!- CATALYTIC ACTIVITY: CC Reaction=4-hydroxyestrone + S-adenosyl-L-methionine = 4-methoxyestrone CC + H(+) + S-adenosyl-L-homocysteine; Xref=Rhea:RHEA:53104, CC ChEBI:CHEBI:15378, ChEBI:CHEBI:57856, ChEBI:CHEBI:59789, CC ChEBI:CHEBI:87602, ChEBI:CHEBI:136972; CC Evidence={ECO:0000250|UniProtKB:P21964}; CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:53105; CC Evidence={ECO:0000250|UniProtKB:P21964}; CC -!- CATALYTIC ACTIVITY: CC Reaction=2-hydroxyestrone + S-adenosyl-L-methionine = 2-methoxyestrone CC + H(+) + S-adenosyl-L-homocysteine; Xref=Rhea:RHEA:53100, CC ChEBI:CHEBI:1156, ChEBI:CHEBI:1189, ChEBI:CHEBI:15378, CC ChEBI:CHEBI:57856, ChEBI:CHEBI:59789; CC Evidence={ECO:0000250|UniProtKB:P21964}; CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:53101; CC Evidence={ECO:0000250|UniProtKB:P21964}; CC -!- CATALYTIC ACTIVITY: CC Reaction=4-hydroxy-17beta-estradiol + S-adenosyl-L-methionine = 4- CC methoxy-17beta-estradiol + H(+) + S-adenosyl-L-homocysteine; CC Xref=Rhea:RHEA:53096, ChEBI:CHEBI:15378, ChEBI:CHEBI:57856, CC ChEBI:CHEBI:59789, ChEBI:CHEBI:62845, ChEBI:CHEBI:136975; CC Evidence={ECO:0000250|UniProtKB:P21964}; CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:53097; CC Evidence={ECO:0000250|UniProtKB:P21964}; CC -!- CATALYTIC ACTIVITY: CC Reaction=2-hydroxy-17beta-estradiol + S-adenosyl-L-methionine = 2- CC hydroxy-3-methoxy-17beta-estradiol + H(+) + S-adenosyl-L- CC homocysteine; Xref=Rhea:RHEA:53092, ChEBI:CHEBI:15378, CC ChEBI:CHEBI:28744, ChEBI:CHEBI:57856, ChEBI:CHEBI:59789, CC ChEBI:CHEBI:89268; Evidence={ECO:0000250|UniProtKB:P21964}; CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:53093; CC Evidence={ECO:0000250|UniProtKB:P21964}; CC -!- CATALYTIC ACTIVITY: CC Reaction=2-hydroxy-17beta-estradiol + S-adenosyl-L-methionine = 2- CC methoxy-17beta-estradiol + H(+) + S-adenosyl-L-homocysteine; CC Xref=Rhea:RHEA:53088, ChEBI:CHEBI:15378, ChEBI:CHEBI:28744, CC ChEBI:CHEBI:28955, ChEBI:CHEBI:57856, ChEBI:CHEBI:59789; CC Evidence={ECO:0000250|UniProtKB:P21964}; CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:53089; CC Evidence={ECO:0000250|UniProtKB:P21964}; CC -!- COFACTOR: CC Name=Mg(2+); Xref=ChEBI:CHEBI:18420; CC Evidence={ECO:0000250|UniProtKB:P22734}; CC Note=Binds 1 Mg(2+) ion per subunit. {ECO:0000250|UniProtKB:P22734}; CC -!- SUBCELLULAR LOCATION: [Isoform Soluble]: Cytoplasm CC {ECO:0000250|UniProtKB:P22734}. CC -!- SUBCELLULAR LOCATION: [Isoform Membrane-bound]: Cell membrane CC {ECO:0000250|UniProtKB:P22734}; Single-pass type II membrane protein CC {ECO:0000255}; Extracellular side {ECO:0000250|UniProtKB:P22734}. CC -!- ALTERNATIVE PRODUCTS: CC Event=Alternative initiation; Named isoforms=2; CC Name=Membrane-bound; Synonyms=MB-COMT; CC IsoId=O88587-1; Sequence=Displayed; CC Name=Soluble; Synonyms=S-COMT; CC IsoId=O88587-2; Sequence=VSP_018779; CC -!- SIMILARITY: Belongs to the class I-like SAM-binding methyltransferase CC superfamily. Cation-dependent O-methyltransferase family. CC {ECO:0000255|PROSITE-ProRule:PRU01019}. CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- DR EMBL; AF076156; AAC33334.1; -; mRNA. DR EMBL; AK148311; BAE28473.1; -; mRNA. DR EMBL; AC133487; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; BC010402; AAH10402.1; -; mRNA. DR CCDS; CCDS28021.1; -. [O88587-1] DR RefSeq; NP_001104532.1; NM_001111062.1. [O88587-1] DR RefSeq; NP_001104533.1; NM_001111063.1. [O88587-1] DR RefSeq; NP_031770.2; NM_007744.3. [O88587-1] DR PDB; 4P58; X-ray; 2.06 A; A=47-258. DR PDB; 4P7F; X-ray; 1.37 A; A=44-265. DR PDBsum; 4P58; -. DR PDBsum; 4P7F; -. DR AlphaFoldDB; O88587; -. DR SMR; O88587; -. DR BioGRID; 198834; 1. DR STRING; 10090.ENSMUSP00000130077; -. DR BindingDB; O88587; -. DR ChEMBL; CHEMBL3286068; -. DR DrugCentral; O88587; -. DR GuidetoPHARMACOLOGY; 2472; -. DR iPTMnet; O88587; -. DR PhosphoSitePlus; O88587; -. DR SwissPalm; O88587; -. DR EPD; O88587; -. DR jPOST; O88587; -. DR MaxQB; O88587; -. DR PaxDb; 10090-ENSMUSP00000111272; -. DR PeptideAtlas; O88587; -. DR ProteomicsDB; 283350; -. [O88587-1] DR ProteomicsDB; 283351; -. [O88587-2] DR Pumba; O88587; -. DR Antibodypedia; 213; 703 antibodies from 41 providers. DR DNASU; 12846; -. DR Ensembl; ENSMUST00000000335.12; ENSMUSP00000000335.5; ENSMUSG00000000326.14. [O88587-1] DR Ensembl; ENSMUST00000115609.10; ENSMUSP00000111272.3; ENSMUSG00000000326.14. [O88587-1] DR Ensembl; ENSMUST00000165430.8; ENSMUSP00000130077.2; ENSMUSG00000000326.14. [O88587-1] DR GeneID; 12846; -. DR KEGG; mmu:12846; -. DR UCSC; uc007ynu.2; mouse. [O88587-1] DR AGR; MGI:88470; -. DR CTD; 1312; -. DR MGI; MGI:88470; Comt. DR VEuPathDB; HostDB:ENSMUSG00000000326; -. DR eggNOG; KOG1663; Eukaryota. DR GeneTree; ENSGT00940000155317; -. DR HOGENOM; CLU_050461_5_0_1; -. DR InParanoid; O88587; -. DR OMA; WNELVLQ; -. DR OrthoDB; 4040098at2759; -. DR PhylomeDB; O88587; -. DR TreeFam; TF329140; -. DR Reactome; R-MMU-156581; Methylation. DR Reactome; R-MMU-379397; Enzymatic degradation of dopamine by COMT. DR Reactome; R-MMU-379398; Enzymatic degradation of Dopamine by monoamine oxidase. DR SABIO-RK; O88587; -. DR BioGRID-ORCS; 12846; 0 hits in 76 CRISPR screens. DR ChiTaRS; Comt; mouse. DR PRO; PR:O88587; -. DR Proteomes; UP000000589; Chromosome 16. DR RNAct; O88587; Protein. DR Bgee; ENSMUSG00000000326; Expressed in white adipose tissue and 115 other cell types or tissues. DR ExpressionAtlas; O88587; baseline and differential. DR GO; GO:0030424; C:axon; ISO:MGI. DR GO; GO:0044297; C:cell body; ISO:MGI. DR GO; GO:0005829; C:cytosol; IDA:MGI. DR GO; GO:0030425; C:dendrite; ISO:MGI. DR GO; GO:0043197; C:dendritic spine; ISO:MGI. DR GO; GO:0098978; C:glutamatergic synapse; ISO:MGI. DR GO; GO:0043231; C:intracellular membrane-bounded organelle; ISO:MGI. DR GO; GO:0016020; C:membrane; IBA:GO_Central. DR GO; GO:0005739; C:mitochondrion; HDA:MGI. DR GO; GO:0098794; C:postsynapse; ISO:MGI. DR GO; GO:0045211; C:postsynaptic membrane; ISO:MGI. DR GO; GO:0031982; C:vesicle; IDA:MGI. DR GO; GO:0016206; F:catechol O-methyltransferase activity; IDA:MGI. DR GO; GO:0102084; F:L-dopa O-methyltransferase activity; IEA:UniProtKB-EC. DR GO; GO:0000287; F:magnesium ion binding; IEA:InterPro. DR GO; GO:0102938; F:orcinol O-methyltransferase activity; IEA:UniProtKB-EC. DR GO; GO:0060840; P:artery development; IMP:MGI. DR GO; GO:0001662; P:behavioral fear response; IMP:MGI. DR GO; GO:0042424; P:catecholamine catabolic process; ISO:MGI. DR GO; GO:0006584; P:catecholamine metabolic process; IMP:MGI. DR GO; GO:0071314; P:cellular response to cocaine; IMP:MGI. DR GO; GO:0016036; P:cellular response to phosphate starvation; IDA:MGI. DR GO; GO:0021696; P:cerebellar cortex morphogenesis; IMP:MGI. DR GO; GO:0033344; P:cholesterol efflux; IMP:MGI. DR GO; GO:0050890; P:cognition; IDA:MGI. DR GO; GO:0050965; P:detection of temperature stimulus involved in sensory perception of pain; IMP:MGI. DR GO; GO:0032502; P:developmental process; IBA:GO_Central. DR GO; GO:0042420; P:dopamine catabolic process; IDA:MGI. DR GO; GO:0042417; P:dopamine metabolic process; IDA:MGI. DR GO; GO:0014046; P:dopamine secretion; IDA:MGI. DR GO; GO:0008210; P:estrogen metabolic process; ISO:MGI. DR GO; GO:0035640; P:exploration behavior; IMP:MGI. DR GO; GO:0042596; P:fear response; IMP:MGI. DR GO; GO:0007565; P:female pregnancy; ISO:MGI. DR GO; GO:0010467; P:gene expression; IMP:MGI. DR GO; GO:0032835; P:glomerulus development; IMP:MGI. DR GO; GO:0005977; P:glycogen metabolic process; IGI:MGI. DR GO; GO:0046959; P:habituation; IMP:MGI. DR GO; GO:0001822; P:kidney development; IMP:MGI. DR GO; GO:0007612; P:learning; IMP:MGI. DR GO; GO:0007611; P:learning or memory; IDA:MGI. DR GO; GO:0071626; P:mastication; IMP:MGI. DR GO; GO:0007613; P:memory; IMP:MGI. DR GO; GO:0032259; P:methylation; ISS:UniProtKB. DR GO; GO:0035264; P:multicellular organism growth; IMP:MGI. DR GO; GO:0048609; P:multicellular organismal reproductive process; ISO:MGI. DR GO; GO:0033555; P:multicellular organismal response to stress; IMP:MGI. DR GO; GO:0045963; P:negative regulation of dopamine metabolic process; ISO:MGI. DR GO; GO:0048662; P:negative regulation of smooth muscle cell proliferation; ISO:MGI. DR GO; GO:0042415; P:norepinephrine metabolic process; IMP:MGI. DR GO; GO:0048243; P:norepinephrine secretion; IMP:MGI. DR GO; GO:0050668; P:positive regulation of homocysteine metabolic process; ISO:MGI. DR GO; GO:0006693; P:prostaglandin metabolic process; IMP:MGI. DR GO; GO:0008217; P:regulation of blood pressure; IMP:MGI. DR GO; GO:0097018; P:renal albumin absorption; IMP:MGI. DR GO; GO:0097205; P:renal filtration; IMP:MGI. DR GO; GO:0035812; P:renal sodium excretion; IMP:MGI. DR GO; GO:0002001; P:renin secretion into blood stream; IMP:MGI. DR GO; GO:0001975; P:response to amphetamine; IMP:MGI. DR GO; GO:1990776; P:response to angiotensin; IMP:MGI. DR GO; GO:0051412; P:response to corticosterone; IMP:MGI. DR GO; GO:0034097; P:response to cytokine; IMP:MGI. DR GO; GO:1903350; P:response to dopamine; IMP:MGI. DR GO; GO:0032094; P:response to food; IMP:MGI. DR GO; GO:0001666; P:response to hypoxia; IMP:MGI. DR GO; GO:0010035; P:response to inorganic substance; IMP:MGI. DR GO; GO:0010033; P:response to organic substance; IMP:MGI. DR GO; GO:0006979; P:response to oxidative stress; IMP:MGI. DR GO; GO:0048265; P:response to pain; ISO:MGI. DR GO; GO:1902074; P:response to salt; IMP:MGI. DR GO; GO:0009266; P:response to temperature stimulus; IMP:MGI. DR GO; GO:0009636; P:response to toxic substance; IMP:MGI. DR GO; GO:0009611; P:response to wounding; IMP:MGI. DR GO; GO:0009410; P:response to xenobiotic stimulus; IMP:MGI. DR GO; GO:0007614; P:short-term memory; ISO:MGI. DR GO; GO:0001964; P:startle response; IMP:MGI. DR GO; GO:0001963; P:synaptic transmission, dopaminergic; IMP:MGI. DR GO; GO:0008542; P:visual learning; IMP:MGI. DR CDD; cd02440; AdoMet_MTases; 1. DR Gene3D; 3.40.50.150; Vaccinia Virus protein VP39; 1. DR InterPro; IPR017128; Catechol_O-MeTrfase_euk. DR InterPro; IPR029063; SAM-dependent_MTases_sf. DR InterPro; IPR002935; SAM_O-MeTrfase. DR PANTHER; PTHR43836:SF3; CATECHOL O-METHYLTRANSFERASE; 1. DR PANTHER; PTHR43836; CATECHOL O-METHYLTRANSFERASE 1-RELATED; 1. DR Pfam; PF01596; Methyltransf_3; 1. DR PIRSF; PIRSF037177; Catechol_O-mtfrase_euk; 1. DR SUPFAM; SSF53335; S-adenosyl-L-methionine-dependent methyltransferases; 1. DR PROSITE; PS51682; SAM_OMT_I; 1. DR Genevisible; O88587; MM. PE 1: Evidence at protein level; KW 3D-structure; Alternative initiation; Catecholamine metabolism; KW Cell membrane; Cytoplasm; Lipid metabolism; Magnesium; Membrane; KW Metal-binding; Methyltransferase; Neurotransmitter degradation; KW Phosphoprotein; Reference proteome; S-adenosyl-L-methionine; Signal-anchor; KW Transferase; Transmembrane; Transmembrane helix. FT CHAIN 1..265 FT /note="Catechol O-methyltransferase" FT /id="PRO_0000020973" FT TOPO_DOM 1..2 FT /note="Cytoplasmic" FT /evidence="ECO:0000255" FT TRANSMEM 3..19 FT /note="Helical; Signal-anchor for type II membrane protein" FT /evidence="ECO:0000255" FT TOPO_DOM 20..265 FT /note="Extracellular" FT /evidence="ECO:0000255" FT BINDING 85 FT /ligand="S-adenosyl-L-methionine" FT /ligand_id="ChEBI:CHEBI:59789" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01019" FT BINDING 107 FT /ligand="S-adenosyl-L-methionine" FT /ligand_id="ChEBI:CHEBI:59789" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01019" FT BINDING 115 FT /ligand="S-adenosyl-L-methionine" FT /ligand_id="ChEBI:CHEBI:59789" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01019" FT BINDING 133 FT /ligand="S-adenosyl-L-methionine" FT /ligand_id="ChEBI:CHEBI:59789" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01019" FT BINDING 134 FT /ligand="S-adenosyl-L-methionine" FT /ligand_id="ChEBI:CHEBI:59789" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01019" FT BINDING 160..163 FT /ligand="S-adenosyl-L-methionine" FT /ligand_id="ChEBI:CHEBI:59789" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01019" FT BINDING 162 FT /ligand="S-adenosyl-L-methionine" FT /ligand_id="ChEBI:CHEBI:59789" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01019" FT BINDING 184 FT /ligand="Mg(2+)" FT /ligand_id="ChEBI:CHEBI:18420" FT /evidence="ECO:0000250" FT BINDING 184 FT /ligand="S-adenosyl-L-methionine" FT /ligand_id="ChEBI:CHEBI:59789" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01019" FT BINDING 187 FT /ligand="substrate" FT /evidence="ECO:0000250" FT BINDING 212 FT /ligand="Mg(2+)" FT /ligand_id="ChEBI:CHEBI:18420" FT /evidence="ECO:0000250" FT BINDING 213 FT /ligand="Mg(2+)" FT /ligand_id="ChEBI:CHEBI:18420" FT /evidence="ECO:0000250" FT BINDING 213 FT /ligand="substrate" FT /evidence="ECO:0000250" FT BINDING 242 FT /ligand="substrate" FT /evidence="ECO:0000250" FT MOD_RES 260 FT /note="Phosphoserine" FT /evidence="ECO:0000250|UniProtKB:P22734" FT MOD_RES 261 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:17242355, FT ECO:0007744|PubMed:19131326, ECO:0007744|PubMed:21183079" FT MOD_RES 265 FT /note="Phosphoserine" FT /evidence="ECO:0000250|UniProtKB:P22734" FT VAR_SEQ 1..43 FT /note="Missing (in isoform Soluble)" FT /evidence="ECO:0000305" FT /id="VSP_018779" FT MUTAGEN 51 FT /note="R->L: Reduces methyltransferase activity against FT norepinephrine." FT /evidence="ECO:0000269|PubMed:18794526" FT CONFLICT 162 FT /note="S -> P (in Ref. 1; AAC33334)" FT /evidence="ECO:0000305" FT HELIX 48..59 FT /evidence="ECO:0007829|PDB:4P7F" FT HELIX 65..78 FT /evidence="ECO:0007829|PDB:4P7F" FT STRAND 81..83 FT /evidence="ECO:0007829|PDB:4P7F" FT HELIX 85..88 FT /evidence="ECO:0007829|PDB:4P7F" FT HELIX 90..100 FT /evidence="ECO:0007829|PDB:4P7F" FT STRAND 103..108 FT /evidence="ECO:0007829|PDB:4P7F" FT STRAND 111..113 FT /evidence="ECO:0007829|PDB:4P7F" FT HELIX 114..120 FT /evidence="ECO:0007829|PDB:4P7F" FT STRAND 128..134 FT /evidence="ECO:0007829|PDB:4P7F" FT HELIX 136..149 FT /evidence="ECO:0007829|PDB:4P7F" FT HELIX 152..154 FT /evidence="ECO:0007829|PDB:4P7F" FT STRAND 155..160 FT /evidence="ECO:0007829|PDB:4P7F" FT HELIX 162..165 FT /evidence="ECO:0007829|PDB:4P7F" FT HELIX 166..168 FT /evidence="ECO:0007829|PDB:4P7F" FT HELIX 169..173 FT /evidence="ECO:0007829|PDB:4P7F" FT STRAND 178..183 FT /evidence="ECO:0007829|PDB:4P7F" FT HELIX 187..189 FT /evidence="ECO:0007829|PDB:4P7F" FT HELIX 190..199 FT /evidence="ECO:0007829|PDB:4P7F" FT STRAND 203..212 FT /evidence="ECO:0007829|PDB:4P7F" FT HELIX 220..228 FT /evidence="ECO:0007829|PDB:4P7F" FT STRAND 232..239 FT /evidence="ECO:0007829|PDB:4P7F" FT STRAND 243..245 FT /evidence="ECO:0007829|PDB:4P7F" FT STRAND 247..255 FT /evidence="ECO:0007829|PDB:4P7F" SQ SEQUENCE 265 AA; 29486 MW; E82E9307F6D8A6CF CRC64; MLLAAVSLGL LLLAFLLLLR HLGWGLVAIG WFEFVQQPVH NLLMGGTKEQ RILRHVQQHA KPGDPQSVLE AIDTYCSEKE WAMNVGDAKG QIMDAVIREY RPSLVLELGA YCGYSAVRMA RLLPPGARLL TMEINPDYAA ITQQMLDFAG LQDKVSILIG ASQDLIPQLK KKYDVDTLDM VFLDHWKDRY LPDTLLLEEC GLLRKGTVLL ADNVIVPGTP DFLAYVRGSS SFECTHYSSY LEYMKVVDGL EKAVYQGPGS SPVKS //