ID COMT_HUMAN Reviewed; 271 AA. AC P21964; A8MPV9; Q6IB07; Q6ICE6; Q9BWC7; DT 01-AUG-1991, integrated into UniProtKB/Swiss-Prot. DT 01-MAY-1992, sequence version 2. DT 27-MAR-2024, entry version 243. DE RecName: Full=Catechol O-methyltransferase {ECO:0000305}; DE EC=2.1.1.6 {ECO:0000269|PubMed:11559542, ECO:0000269|PubMed:15645182, ECO:0000269|PubMed:21846718}; GN Name=COMT {ECO:0000312|HGNC:HGNC:2228}; OS Homo sapiens (Human). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; OC Homo. OX NCBI_TaxID=9606; RN [1] RP NUCLEOTIDE SEQUENCE [MRNA]. RC TISSUE=Placenta; RX PubMed=1707278; DOI=10.1089/dna.1991.10.181; RA Lundstroem K., Salminen M., Jalanko A., Savolainen R., Ulmanen I.; RT "Cloning and characterization of human placental catechol-O- RT methyltransferase cDNA."; RL DNA Cell Biol. 10:181-189(1991). RN [2] RP NUCLEOTIDE SEQUENCE [MRNA], AND VARIANT SER-34. RX PubMed=1847521; DOI=10.1073/pnas.88.4.1416; RA Bertocci B., Miggiano V., da Prada M., Dembic Z., Lahm H.-W., Malherbe P.; RT "Human catechol-O-methyltransferase: cloning and expression of the RT membrane-associated form."; RL Proc. Natl. Acad. Sci. U.S.A. 88:1416-1420(1991). RN [3] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA]. RX PubMed=8055944; DOI=10.1111/j.1432-1033.1994.tb19083.x; RA Tenhunen J., Salminen M., Lundstroem K., Kiviluoto T., Savolainen R., RA Ulmanen I.; RT "Genomic organization of the human catechol O-methyltransferase gene and RT its expression from two distinct promoters."; RL Eur. J. Biochem. 223:1049-1059(1994). RN [4] RP NUCLEOTIDE SEQUENCE [MRNA]. RA Li J.Y., Wang H.Y., Liu J., Liu F.J.; RL Submitted (SEP-2008) to the EMBL/GenBank/DDBJ databases. RN [5] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. RX PubMed=14702039; DOI=10.1038/ng1285; RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S., RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., RA Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., RA Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., RA Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., RA Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., RA Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., RA Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., RA Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., RA Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., RA Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., RA Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., RA Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., RA Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., RA Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., RA Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., RA Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., RA Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., RA Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., RA Isogai T., Sugano S.; RT "Complete sequencing and characterization of 21,243 full-length human RT cDNAs."; RL Nat. Genet. 36:40-45(2004). RN [6] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA], AND VARIANT MET-158. RX PubMed=15461802; DOI=10.1186/gb-2004-5-10-r84; RA Collins J.E., Wright C.L., Edwards C.A., Davis M.P., Grinham J.A., RA Cole C.G., Goward M.E., Aguado B., Mallya M., Mokrab Y., Huckle E.J., RA Beare D.M., Dunham I.; RT "A genome annotation-driven approach to cloning the human ORFeome."; RL Genome Biol. 5:R84.1-R84.11(2004). RN [7] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. RA Ebert L., Schick M., Neubert P., Schatten R., Henze S., Korn B.; RT "Cloning of human full open reading frames in Gateway(TM) system entry RT vector (pDONR201)."; RL Submitted (JUN-2004) to the EMBL/GenBank/DDBJ databases. RN [8] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND VARIANTS SER-72 AND MET-158. RG NIEHS SNPs program; RL Submitted (JUL-2003) to the EMBL/GenBank/DDBJ databases. RN [9] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RX PubMed=10591208; DOI=10.1038/990031; RA Dunham I., Hunt A.R., Collins J.E., Bruskiewich R., Beare D.M., Clamp M., RA Smink L.J., Ainscough R., Almeida J.P., Babbage A.K., Bagguley C., RA Bailey J., Barlow K.F., Bates K.N., Beasley O.P., Bird C.P., Blakey S.E., RA Bridgeman A.M., Buck D., Burgess J., Burrill W.D., Burton J., Carder C., RA Carter N.P., Chen Y., Clark G., Clegg S.M., Cobley V.E., Cole C.G., RA Collier R.E., Connor R., Conroy D., Corby N.R., Coville G.J., Cox A.V., RA Davis J., Dawson E., Dhami P.D., Dockree C., Dodsworth S.J., Durbin R.M., RA Ellington A.G., Evans K.L., Fey J.M., Fleming K., French L., Garner A.A., RA Gilbert J.G.R., Goward M.E., Grafham D.V., Griffiths M.N.D., Hall C., RA Hall R.E., Hall-Tamlyn G., Heathcott R.W., Ho S., Holmes S., Hunt S.E., RA Jones M.C., Kershaw J., Kimberley A.M., King A., Laird G.K., Langford C.F., RA Leversha M.A., Lloyd C., Lloyd D.M., Martyn I.D., Mashreghi-Mohammadi M., RA Matthews L.H., Mccann O.T., Mcclay J., Mclaren S., McMurray A.A., RA Milne S.A., Mortimore B.J., Odell C.N., Pavitt R., Pearce A.V., Pearson D., RA Phillimore B.J.C.T., Phillips S.H., Plumb R.W., Ramsay H., Ramsey Y., RA Rogers L., Ross M.T., Scott C.E., Sehra H.K., Skuce C.D., Smalley S., RA Smith M.L., Soderlund C., Spragon L., Steward C.A., Sulston J.E., RA Swann R.M., Vaudin M., Wall M., Wallis J.M., Whiteley M.N., Willey D.L., RA Williams L., Williams S.A., Williamson H., Wilmer T.E., Wilming L., RA Wright C.L., Hubbard T., Bentley D.R., Beck S., Rogers J., Shimizu N., RA Minoshima S., Kawasaki K., Sasaki T., Asakawa S., Kudoh J., Shintani A., RA Shibuya K., Yoshizaki Y., Aoki N., Mitsuyama S., Roe B.A., Chen F., Chu L., RA Crabtree J., Deschamps S., Do A., Do T., Dorman A., Fang F., Fu Y., Hu P., RA Hua A., Kenton S., Lai H., Lao H.I., Lewis J., Lewis S., Lin S.-P., Loh P., RA Malaj E., Nguyen T., Pan H., Phan S., Qi S., Qian Y., Ray L., Ren Q., RA Shaull S., Sloan D., Song L., Wang Q., Wang Y., Wang Z., White J., RA Willingham D., Wu H., Yao Z., Zhan M., Zhang G., Chissoe S., Murray J., RA Miller N., Minx P., Fulton R., Johnson D., Bemis G., Bentley D., RA Bradshaw H., Bourne S., Cordes M., Du Z., Fulton L., Goela D., Graves T., RA Hawkins J., Hinds K., Kemp K., Latreille P., Layman D., Ozersky P., RA Rohlfing T., Scheet P., Walker C., Wamsley A., Wohldmann P., Pepin K., RA Nelson J., Korf I., Bedell J.A., Hillier L.W., Mardis E., Waterston R., RA Wilson R., Emanuel B.S., Shaikh T., Kurahashi H., Saitta S., Budarf M.L., RA McDermid H.E., Johnson A., Wong A.C.C., Morrow B.E., Edelmann L., Kim U.J., RA Shizuya H., Simon M.I., Dumanski J.P., Peyrard M., Kedra D., Seroussi E., RA Fransson I., Tapia I., Bruder C.E., O'Brien K.P., Wilkinson P., RA Bodenteich A., Hartman K., Hu X., Khan A.S., Lane L., Tilahun Y., RA Wright H.; RT "The DNA sequence of human chromosome 22."; RL Nature 402:489-495(1999). RN [10] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA], AND VARIANT MET-158. RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M., RA Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., RA Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., RA Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., RA Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., RA Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., RA Hunkapiller M.W., Myers E.W., Venter J.C.; RL Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases. RN [11] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. RC TISSUE=Brain, Muscle, and Skin; 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 [12] RP PROTEIN SEQUENCE OF 52-61. RX PubMed=8020475; DOI=10.1111/j.1432-1033.1994.tb18876.x; RA Vilbois F., Caspers P., da Prada M., Lang G., Karrer C., Lahm H.W., RA Cesura A.M.; RT "Mass spectrometric analysis of human soluble catechol O-methyltransferase RT expressed in Escherichia coli. Identification of a product of ribosomal RT frameshifting and of reactive cysteines involved in S-adenosyl-L-methionine RT binding."; RL Eur. J. Biochem. 222:377-386(1994). RN [13] RP PROTEIN SEQUENCE OF 59-271. RC TISSUE=Placenta; RX PubMed=1993083; DOI=10.1016/0006-291x(91)91517-g; RA Tilgmann C., Kalkkinen N.; RT "Purification and partial sequence analysis of the soluble catechol-O- RT methyltransferase from human placenta: comparison to the rat liver RT enzyme."; RL Biochem. Biophys. Res. Commun. 174:995-1002(1991). RN [14] RP CHARACTERIZATION OF THE TWO FORMS. RX PubMed=1765063; DOI=10.1111/j.1432-1033.1991.tb16464.x; RA Ulmanen I., Lundstroem K.; RT "Cell-free synthesis of rat and human catechol O-methyltransferase. RT Insertion of the membrane-bound form into microsomal membranes in vitro."; RL Eur. J. Biochem. 202:1013-1020(1991). RN [15] RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RX PubMed=21269460; DOI=10.1186/1752-0509-5-17; RA Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T., RA Bennett K.L., Superti-Furga G., Colinge J.; RT "Initial characterization of the human central proteome."; RL BMC Syst. Biol. 5:17-17(2011). RN [16] RP FUNCTION, CATALYTIC ACTIVITY, SUBCELLULAR LOCATION, AND TOPOLOGY. RX PubMed=21846718; DOI=10.1074/jbc.m111.262790; RA Chen J., Song J., Yuan P., Tian Q., Ji Y., Ren-Patterson R., Liu G., RA Sei Y., Weinberger D.R.; RT "Orientation and cellular distribution of membrane-bound catechol-O- RT methyltransferase in cortical neurons: implications for drug development."; RL J. Biol. Chem. 286:34752-34760(2011). RN [17] RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Liver; RX PubMed=24275569; DOI=10.1016/j.jprot.2013.11.014; RA Bian Y., Song C., Cheng K., Dong M., Wang F., Huang J., Sun D., Wang L., RA Ye M., Zou H.; RT "An enzyme assisted RP-RPLC approach for in-depth analysis of human liver RT phosphoproteome."; RL J. Proteomics 96:253-262(2014). RN [18] RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RX PubMed=25944712; DOI=10.1002/pmic.201400617; RA Vaca Jacome A.S., Rabilloud T., Schaeffer-Reiss C., Rompais M., Ayoub D., RA Lane L., Bairoch A., Van Dorsselaer A., Carapito C.; RT "N-terminome analysis of the human mitochondrial proteome."; RL Proteomics 15:2519-2524(2015). RN [19] RP X-RAY CRYSTALLOGRAPHY (1.3 ANGSTROMS) OF 52-264 OF MUTANTS VAL-108 AND RP MET-108 IN COMPLEX WITH SUBSTRATE ANALOG 3,5-DINITROCATECHOL; MAGNESIUM AND RP S-ADENOSYL-L-METHIONINE. RX PubMed=18486144; DOI=10.1016/j.jmb.2008.04.040; RA Rutherford K., Le Trong I., Stenkamp R.E., Parson W.W.; RT "Crystal structures of human 108V and 108M catechol O-methyltransferase."; RL J. Mol. Biol. 380:120-130(2008). RN [20] RP VARIANT COMT*2 MET-158. RX PubMed=8807664; DOI=10.1097/00008571-199606000-00007; RA Lachman H.M., Papolos D.F., Saito T., Yu Y.-M., Szumlanski C.L., RA Weinshilboum R.M.; RT "Human catechol-O-methyltransferase pharmacogenetics: description of a RT functional polymorphism and its potential application to neuropsychiatric RT disorders."; RL Pharmacogenetics 6:243-250(1996). RN [21] RP INVOLVEMENT IN SUSCEPTIBILITY TO ALCOHOLISM. RX PubMed=10395222; DOI=10.1038/sj.mp.4000509; RA Tiihonen J., Hallikainen T., Lachman H., Saito T., Volavka J., Kauhanen J., RA Salonen J.T., Ryynaenen O.-P., Koulu M., Karvonen M.K., Pohjalainen T., RA Syvaelahti E., Hietala J.; RT "Association between the functional variant of the catechol-O- RT methyltransferase (COMT) gene and type 1 alcoholism."; RL Mol. Psychiatry 4:286-289(1999). RN [22] RP VARIANTS SER-34 AND SER-72. RX PubMed=10391209; DOI=10.1038/10290; RA Cargill M., Altshuler D., Ireland J., Sklar P., Ardlie K., Patil N., RA Shaw N., Lane C.R., Lim E.P., Kalyanaraman N., Nemesh J., Ziaugra L., RA Friedland L., Rolfe A., Warrington J., Lipshutz R., Daley G.Q., RA Lander E.S.; RT "Characterization of single-nucleotide polymorphisms in coding regions of RT human genes."; RL Nat. Genet. 22:231-238(1999). RN [23] RP ERRATUM OF PUBMED:10391209. RA Cargill M., Altshuler D., Ireland J., Sklar P., Ardlie K., Patil N., RA Shaw N., Lane C.R., Lim E.P., Kalyanaraman N., Nemesh J., Ziaugra L., RA Friedland L., Rolfe A., Warrington J., Lipshutz R., Daley G.Q., RA Lander E.S.; RL Nat. Genet. 23:373-373(1999). RN [24] RP CHARACTERIZATION OF VARIANT COMT*2 MET-158, FUNCTION, CATALYTIC ACTIVITY, RP BIOPHYSICOCHEMICAL PROPERTIES, AND SUBCELLULAR LOCATION. RX PubMed=11559542; RA Dawling S., Roodi N., Mernaugh R.L., Wang X., Parl F.F.; RT "Catechol-O-methyltransferase (COMT)-mediated metabolism of catechol RT estrogens: comparison of wild-type and variant COMT isoforms."; RL Cancer Res. 61:6716-6722(2001). RN [25] RP CHARACTERIZATION OF VARIANT SER-72, INVOLVEMENT IN SCZD, AND CATALYTIC RP ACTIVITY. RX PubMed=15645182; DOI=10.1007/s00439-004-1239-y; RA Lee S.-G., Joo Y., Kim B., Chung S., Kim H.-L., Lee I., Choi B., Kim C., RA Song K.; RT "Association of Ala72Ser polymorphism with COMT enzyme activity and the RT risk of schizophrenia in Koreans."; RL Hum. Genet. 116:319-328(2005). RN [26] RP CHARACTERIZATION OF VARIANT COMT*2 MET-158. RX PubMed=18474266; DOI=10.1016/j.bbapap.2008.04.006; RA Rutherford K., Alphandery E., McMillan A., Daggett V., Parson W.W.; RT "The V108M mutation decreases the structural stability of catechol O- RT methyltransferase."; RL Biochim. Biophys. Acta 1784:1098-1105(2008). RN [27] RP VARIANT COMT*2 MET-158. RX PubMed=18442637; DOI=10.1016/j.metabol.2008.01.012; RA Annerbrink K., Westberg L., Nilsson S., Rosmond R., Holm G., Eriksson E.; RT "Catechol O-methyltransferase val158-met polymorphism is associated with RT abdominal obesity and blood pressure in men."; RL Metabolism 57:708-711(2008). 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:11559542, CC ECO:0000269|PubMed:21846718}. 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:0000269|PubMed:15645182, ECO:0000269|PubMed:21846718}; CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:17878; CC Evidence={ECO:0000305|PubMed:11559542}; 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:0000269|PubMed:11559542}; CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:53109; CC Evidence={ECO:0000305|PubMed:11559542}; 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:0000269|PubMed:11559542}; CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:53105; CC Evidence={ECO:0000305|PubMed:11559542}; 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:0000269|PubMed:11559542}; CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:53101; CC Evidence={ECO:0000305|PubMed:11559542}; 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:0000269|PubMed:11559542}; CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:53097; CC Evidence={ECO:0000305|PubMed:11559542}; 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:0000269|PubMed:11559542}; CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:53093; CC Evidence={ECO:0000305|PubMed:11559542}; 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:0000269|PubMed:11559542}; CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:53089; CC Evidence={ECO:0000305|PubMed:11559542}; 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 -!- BIOPHYSICOCHEMICAL PROPERTIES: CC Kinetic parameters: CC KM=108 uM for 2-hydroxy-17beta-estradiol (at 37 degrees Celsius) CC {ECO:0000269|PubMed:11559542}; CC KM=24 uM for 4-hydroxy-17beta-estradiol (at 37 degrees Celsius) CC {ECO:0000269|PubMed:11559542}; CC KM=74 uM for 2-hydroxyestrone (at 37 degrees Celsius) CC {ECO:0000269|PubMed:11559542}; CC KM=53 uM for 4-hydroxyestrone (at 37 degrees Celsius) CC {ECO:0000269|PubMed:11559542}; CC Note=kcats are 6.8 min(-1), 3.4 min(-1), 3.3 min(-1) and 6.7 min(-1) CC with 2-hydroxy-17beta-estradiol, 4-hydroxy-17beta-estradiol, CC 2-hydroxyestrone and 4-hydroxyestrone as subrates, respectively. CC {ECO:0000269|PubMed:11559542}; CC -!- INTERACTION: CC P21964; Q6P5T0: AQP7; NbExp=3; IntAct=EBI-372265, EBI-10489564; CC P21964; P30518: AVPR2; NbExp=3; IntAct=EBI-372265, EBI-11675746; CC P21964; Q8NFU1: BEST2; NbExp=3; IntAct=EBI-372265, EBI-19947314; CC P21964; Q8NHW4: CCL4L2; NbExp=3; IntAct=EBI-372265, EBI-10271156; CC P21964; P34972: CNR2; NbExp=3; IntAct=EBI-372265, EBI-2835940; CC P21964; Q96BA8: CREB3L1; NbExp=3; IntAct=EBI-372265, EBI-6942903; CC P21964; P50402: EMD; NbExp=3; IntAct=EBI-372265, EBI-489887; CC P21964; Q5JX71: FAM209A; NbExp=3; IntAct=EBI-372265, EBI-18304435; CC P21964; O14843: FFAR3; NbExp=3; IntAct=EBI-372265, EBI-17762181; CC P21964; O00258: GET1; NbExp=3; IntAct=EBI-372265, EBI-18908258; CC P21964; P08034: GJB1; NbExp=3; IntAct=EBI-372265, EBI-17565645; CC P21964; O75712: GJB3; NbExp=3; IntAct=EBI-372265, EBI-3908586; CC P21964; Q9NTQ9: GJB4; NbExp=3; IntAct=EBI-372265, EBI-12831526; CC P21964; O95377: GJB5; NbExp=3; IntAct=EBI-372265, EBI-3909454; CC P21964; Q8TDT2: GPR152; NbExp=3; IntAct=EBI-372265, EBI-13345167; CC P21964; Q8N6U8: GPR161; NbExp=3; IntAct=EBI-372265, EBI-6255622; CC P21964; O15529: GPR42; NbExp=3; IntAct=EBI-372265, EBI-18076404; CC P21964; P31937: HIBADH; NbExp=3; IntAct=EBI-372265, EBI-11427100; CC P21964; Q9H2F3: HSD3B7; NbExp=3; IntAct=EBI-372265, EBI-3918847; CC P21964; O95279: KCNK5; NbExp=3; IntAct=EBI-372265, EBI-3934936; CC P21964; Q5SR56: MFSD14B; NbExp=3; IntAct=EBI-372265, EBI-373355; CC P21964; A6NDP7: MYADML2; NbExp=3; IntAct=EBI-372265, EBI-17641390; CC P21964; Q0D2K0: NIPAL4; NbExp=3; IntAct=EBI-372265, EBI-9550165; CC P21964; Q7RTS5: OTOP3; NbExp=3; IntAct=EBI-372265, EBI-12853910; CC P21964; Q9UHJ9-5: PGAP2; NbExp=3; IntAct=EBI-372265, EBI-12092917; CC P21964; Q8IY26: PLPP6; NbExp=3; IntAct=EBI-372265, EBI-11721828; CC P21964; Q9H6H4: REEP4; NbExp=3; IntAct=EBI-372265, EBI-7545592; CC P21964; Q6NTF9-3: RHBDD2; NbExp=3; IntAct=EBI-372265, EBI-17589229; CC P21964; O75783: RHBDL1; NbExp=3; IntAct=EBI-372265, EBI-12104986; CC P21964; Q99500: S1PR3; NbExp=3; IntAct=EBI-372265, EBI-10634734; CC P21964; Q9Y6D0: SELENOK; NbExp=3; IntAct=EBI-372265, EBI-9679163; CC P21964; Q3KNW5: SLC10A6; NbExp=3; IntAct=EBI-372265, EBI-18159983; CC P21964; O60669: SLC16A7; NbExp=3; IntAct=EBI-372265, EBI-3921243; CC P21964; P22732: SLC2A5; NbExp=3; IntAct=EBI-372265, EBI-2825135; CC P21964; Q96G79: SLC35A4; NbExp=3; IntAct=EBI-372265, EBI-12363689; CC P21964; Q5T1Q4: SLC35F1; NbExp=3; IntAct=EBI-372265, EBI-13365456; CC P21964; Q9NY26: SLC39A1; NbExp=3; IntAct=EBI-372265, EBI-726491; CC P21964; Q9NP94: SLC39A2; NbExp=3; IntAct=EBI-372265, EBI-12898013; CC P21964; Q6P1K1: SLC48A1; NbExp=3; IntAct=EBI-372265, EBI-1222191; CC P21964; P30825: SLC7A1; NbExp=3; IntAct=EBI-372265, EBI-4289564; CC P21964; Q9UHI5: SLC7A8; NbExp=3; IntAct=EBI-372265, EBI-13292283; CC P21964; B2RUZ4: SMIM1; NbExp=3; IntAct=EBI-372265, EBI-12188413; CC P21964; Q9UPZ6: THSD7A; NbExp=3; IntAct=EBI-372265, EBI-310962; CC P21964; Q96MV1: TLCD4; NbExp=3; IntAct=EBI-372265, EBI-12947623; CC P21964; Q9NV29: TMEM100; NbExp=3; IntAct=EBI-372265, EBI-8644968; CC P21964; A0PK00: TMEM120B; NbExp=3; IntAct=EBI-372265, EBI-10171534; CC P21964; Q9NUH8: TMEM14B; NbExp=3; IntAct=EBI-372265, EBI-8638294; CC P21964; Q9P0S9: TMEM14C; NbExp=3; IntAct=EBI-372265, EBI-2339195; CC P21964; Q14656: TMEM187; NbExp=3; IntAct=EBI-372265, EBI-13046724; CC P21964; Q6UW68: TMEM205; NbExp=3; IntAct=EBI-372265, EBI-6269551; CC P21964; Q9H0R3: TMEM222; NbExp=3; IntAct=EBI-372265, EBI-347385; CC P21964; O95807: TMEM50A; NbExp=3; IntAct=EBI-372265, EBI-12903814; CC P21964; P34981: TRHR; NbExp=3; IntAct=EBI-372265, EBI-18055230; CC P21964; Q15645: TRIP13; NbExp=3; IntAct=EBI-372265, EBI-358993; CC P21964; Q15836: VAMP3; NbExp=3; IntAct=EBI-372265, EBI-722343; CC P21964; O95183: VAMP5; NbExp=3; IntAct=EBI-372265, EBI-10191195; CC P21964; O76024: WFS1; NbExp=3; IntAct=EBI-372265, EBI-720609; CC P21964-2; P30260: CDC27; NbExp=3; IntAct=EBI-10200977, EBI-994813; CC P21964-2; Q9H816: DCLRE1B; NbExp=3; IntAct=EBI-10200977, EBI-3508943; CC P21964-2; Q92997: DVL3; NbExp=3; IntAct=EBI-10200977, EBI-739789; CC P21964-2; P29323-3: EPHB2; NbExp=3; IntAct=EBI-10200977, EBI-25838727; CC P21964-2; P22607: FGFR3; NbExp=3; IntAct=EBI-10200977, EBI-348399; CC P21964-2; P06396: GSN; NbExp=3; IntAct=EBI-10200977, EBI-351506; CC P21964-2; Q15323: KRT31; NbExp=3; IntAct=EBI-10200977, EBI-948001; CC P21964-2; Q6A162: KRT40; NbExp=3; IntAct=EBI-10200977, EBI-10171697; CC P21964-2; P26371: KRTAP5-9; NbExp=3; IntAct=EBI-10200977, EBI-3958099; CC P21964-2; O15116: LSM1; NbExp=3; IntAct=EBI-10200977, EBI-347619; CC P21964-2; P20645: M6PR; NbExp=3; IntAct=EBI-10200977, EBI-2907262; CC P21964-2; O14744: PRMT5; NbExp=3; IntAct=EBI-10200977, EBI-351098; CC P21964-2; Q5T160: RARS2; NbExp=3; IntAct=EBI-10200977, EBI-1050546; CC P21964-2; Q9UJD0: RIMS3; NbExp=3; IntAct=EBI-10200977, EBI-3909436; CC P21964-2; Q2MKA7: RSPO1; NbExp=3; IntAct=EBI-10200977, EBI-10045219; CC P21964-2; Q8N488: RYBP; NbExp=3; IntAct=EBI-10200977, EBI-752324; CC P21964-2; O75880: SCO1; NbExp=3; IntAct=EBI-10200977, EBI-6656171; CC P21964-2; Q14141: SEPTIN6; NbExp=3; IntAct=EBI-10200977, EBI-745901; CC P21964-2; Q9UNE7: STUB1; NbExp=3; IntAct=EBI-10200977, EBI-357085; CC P21964-2; Q15645: TRIP13; NbExp=3; IntAct=EBI-10200977, EBI-358993; CC P21964-2; Q9NYH9: UTP6; NbExp=3; IntAct=EBI-10200977, EBI-749211; CC P21964-2; Q8NA23-2: WDR31; NbExp=3; IntAct=EBI-10200977, EBI-25835937; CC -!- SUBCELLULAR LOCATION: [Isoform Soluble]: Cytoplasm CC {ECO:0000269|PubMed:11559542}. CC -!- SUBCELLULAR LOCATION: [Isoform Membrane-bound]: Cell membrane CC {ECO:0000269|PubMed:21846718}; Single-pass type II membrane protein CC {ECO:0000269|PubMed:21846718}; Extracellular side CC {ECO:0000269|PubMed:21846718}. CC -!- ALTERNATIVE PRODUCTS: CC Event=Alternative initiation; Named isoforms=2; CC Name=Membrane-bound; Synonyms=MB-COMT; CC IsoId=P21964-1; Sequence=Displayed; CC Name=Soluble; Synonyms=S-COMT; CC IsoId=P21964-2; Sequence=VSP_018778; CC -!- TISSUE SPECIFICITY: Brain, liver, placenta, lymphocytes and CC erythrocytes. CC -!- PTM: The N-terminus is blocked. CC -!- POLYMORPHISM: Two alleles, COMT*1 or COMT*H with Val-158 and COMT*2 or CC COMT*L with Met-158 are responsible for a three to four-fold difference CC in enzymatic activity. {ECO:0000269|PubMed:11559542, CC ECO:0000269|PubMed:18442637, ECO:0000269|PubMed:18474266, CC ECO:0000269|PubMed:8807664}. CC -!- POLYMORPHISM: Low enzyme activity alleles are associated with genetic CC susceptibility to alcoholism [MIM:103780]. CC {ECO:0000269|PubMed:10395222}. CC -!- DISEASE: Schizophrenia (SCZD) [MIM:181500]: A complex, multifactorial CC psychotic disorder or group of disorders characterized by disturbances CC in the form and content of thought (e.g. delusions, hallucinations), in CC mood (e.g. inappropriate affect), in sense of self and relationship to CC the external world (e.g. loss of ego boundaries, withdrawal), and in CC behavior (e.g bizarre or apparently purposeless behavior). Although it CC affects emotions, it is distinguished from mood disorders in which such CC disturbances are primary. Similarly, there may be mild impairment of CC cognitive function, and it is distinguished from the dementias in which CC disturbed cognitive function is considered primary. Some patients CC manifest schizophrenic as well as bipolar disorder symptoms and are CC often given the diagnosis of schizoaffective disorder. CC {ECO:0000269|PubMed:15645182}. Note=Disease susceptibility may be CC associated with variants affecting the gene represented in this entry. 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 -!- SEQUENCE CAUTION: CC Sequence=AAH00419.2; Type=Erroneous termination; Note=Truncated C-terminus.; Evidence={ECO:0000305}; CC Sequence=AAH05867.1; Type=Erroneous termination; Note=Truncated C-terminus.; Evidence={ECO:0000305}; CC Sequence=ACI46037.1; Type=Erroneous termination; Note=Truncated C-terminus.; Evidence={ECO:0000305}; CC -!- WEB RESOURCE: Name=NIEHS-SNPs; CC URL="http://egp.gs.washington.edu/data/comt/"; CC -!- WEB RESOURCE: Name=Wikipedia; Note=Catechol-O-methyl transferase entry; CC URL="https://en.wikipedia.org/wiki/Catechol-O-methyl_transferase"; 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; M65212; AAA68927.1; -; mRNA. DR EMBL; M65213; AAA68928.1; -; mRNA. DR EMBL; M58525; AAA68929.1; -; mRNA. DR EMBL; Z26491; CAA81263.1; -; Genomic_DNA. DR EMBL; FJ224345; ACI46037.1; ALT_TERM; mRNA. DR EMBL; AK290440; BAF83129.1; -; mRNA. DR EMBL; CR456422; CAG30308.1; -; mRNA. DR EMBL; CR456997; CAG33278.1; -; mRNA. DR EMBL; AY341246; AAP88929.1; -; Genomic_DNA. DR EMBL; AC000080; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; AC000090; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; AC005663; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; CH471176; EAX03010.1; -; Genomic_DNA. DR EMBL; BC000419; AAH00419.2; ALT_TERM; mRNA. DR EMBL; BC005867; AAH05867.1; ALT_TERM; mRNA. DR EMBL; BC011935; AAH11935.1; -; mRNA. DR EMBL; BC100018; AAI00019.1; -; mRNA. DR CCDS; CCDS13770.1; -. [P21964-1] DR CCDS; CCDS46663.1; -. [P21964-2] DR PIR; I37256; A38459. DR RefSeq; NP_000745.1; NM_000754.3. [P21964-1] DR RefSeq; NP_001128633.1; NM_001135161.1. [P21964-1] DR RefSeq; NP_001128634.1; NM_001135162.1. [P21964-1] DR RefSeq; NP_009294.1; NM_007310.2. [P21964-2] DR RefSeq; XP_016884083.1; XM_017028594.1. DR RefSeq; XP_016884084.1; XM_017028595.1. DR PDB; 3A7E; X-ray; 2.80 A; A=51-264. DR PDB; 3BWM; X-ray; 1.98 A; A=52-265. DR PDB; 3BWY; X-ray; 1.30 A; A=52-265. DR PDB; 4PYI; X-ray; 1.35 A; A=51-271. DR PDB; 4PYJ; X-ray; 1.90 A; A=51-271. DR PDB; 4PYK; X-ray; 2.22 A; A=51-271. DR PDB; 4XUC; X-ray; 1.80 A; A=48-265. DR PDB; 4XUD; X-ray; 2.40 A; A=48-265. DR PDB; 4XUE; X-ray; 2.30 A; A/B=52-265. DR PDB; 5LSA; X-ray; 1.50 A; A=51-271. DR PDB; 6I3C; X-ray; 1.34 A; A=52-271. DR PDB; 6I3D; X-ray; 1.45 A; A/B=52-271. DR PDBsum; 3A7E; -. DR PDBsum; 3BWM; -. DR PDBsum; 3BWY; -. DR PDBsum; 4PYI; -. DR PDBsum; 4PYJ; -. DR PDBsum; 4PYK; -. DR PDBsum; 4XUC; -. DR PDBsum; 4XUD; -. DR PDBsum; 4XUE; -. DR PDBsum; 5LSA; -. DR PDBsum; 6I3C; -. DR PDBsum; 6I3D; -. DR AlphaFoldDB; P21964; -. DR SMR; P21964; -. DR BioGRID; 107707; 170. DR IntAct; P21964; 114. DR MINT; P21964; -. DR STRING; 9606.ENSP00000354511; -. DR BindingDB; P21964; -. DR ChEMBL; CHEMBL2023; -. DR DrugBank; DB07462; (3,4-DIHYDROXY-2-NITROPHENYL)(PHENYL)METHANONE. DR DrugBank; DB02342; 2-Methoxyestradiol. DR DrugBank; DB02105; 3,5-Dinitrocatechol. DR DrugBank; DB08049; 7,8-dihydroxy-4-phenyl-2H-chromen-2-one. DR DrugBank; DB00118; Ademetionine. DR DrugBank; DB00714; Apomorphine. DR DrugBank; DB03336; BIA. DR DrugBank; DB00286; Conjugated estrogens. DR DrugBank; DB00255; Diethylstilbestrol. DR DrugBank; DB00841; Dobutamine. DR DrugBank; DB00988; Dopamine. DR DrugBank; DB15488; Echinacoside. DR DrugBank; DB00494; Entacapone. DR DrugBank; DB00668; Epinephrine. DR DrugBank; DB00783; Estradiol. DR DrugBank; DB00977; Ethinylestradiol. DR DrugBank; DB01064; Isoprenaline. DR DrugBank; DB00968; Methyldopa. DR DrugBank; DB01141; Micafungin. DR DrugBank; DB03907; N-[(E)-3-[(2R,3S,4R,5R)-5-(6-Aminopurin-9-yl)-3,4-dihydroxyoxolan-2-yl]prop-2-enyl]-2,3-dihydroxy-5-nitrobenzamide. DR DrugBank; DB04820; Nialamide. DR DrugBank; DB06152; Nylidrin. DR DrugBank; DB11632; Opicapone. DR DrugBank; DB00252; Phenytoin. DR DrugBank; DB01420; Testosterone propionate. DR DrugBank; DB00323; Tolcapone. DR DrugCentral; P21964; -. DR GuidetoPHARMACOLOGY; 2472; -. DR SwissLipids; SLP:000001714; -. [P21964-2] DR GlyGen; P21964; 1 site, 1 O-linked glycan (1 site). DR iPTMnet; P21964; -. DR MetOSite; P21964; -. DR PhosphoSitePlus; P21964; -. DR SwissPalm; P21964; -. DR BioMuta; COMT; -. DR DMDM; 116907; -. DR REPRODUCTION-2DPAGE; IPI00375513; -. DR CPTAC; CPTAC-482; -. DR CPTAC; CPTAC-483; -. DR EPD; P21964; -. DR jPOST; P21964; -. DR MassIVE; P21964; -. DR MaxQB; P21964; -. DR PaxDb; 9606-ENSP00000354511; -. DR PeptideAtlas; P21964; -. DR PRIDE; P21964; -. DR ProteomicsDB; 53945; -. [P21964-1] DR ProteomicsDB; 53946; -. [P21964-2] DR Pumba; P21964; -. DR TopDownProteomics; P21964-1; -. [P21964-1] DR TopDownProteomics; P21964-2; -. [P21964-2] DR Antibodypedia; 213; 703 antibodies from 41 providers. DR DNASU; 1312; -. DR Ensembl; ENST00000361682.11; ENSP00000354511.6; ENSG00000093010.15. [P21964-1] DR Ensembl; ENST00000403710.5; ENSP00000385917.1; ENSG00000093010.15. [P21964-1] DR Ensembl; ENST00000406520.7; ENSP00000385150.3; ENSG00000093010.15. [P21964-1] DR Ensembl; ENST00000407537.5; ENSP00000384654.2; ENSG00000093010.15. [P21964-1] DR Ensembl; ENST00000449653.5; ENSP00000416778.1; ENSG00000093010.15. [P21964-2] DR Ensembl; ENST00000676678.1; ENSP00000503719.1; ENSG00000093010.15. [P21964-1] DR Ensembl; ENST00000678255.1; ENSP00000504402.1; ENSG00000093010.15. [P21964-1] DR Ensembl; ENST00000678868.1; ENSP00000503583.1; ENSG00000093010.15. [P21964-1] DR GeneID; 1312; -. DR KEGG; hsa:1312; -. DR MANE-Select; ENST00000361682.11; ENSP00000354511.6; NM_000754.4; NP_000745.1. DR UCSC; uc002zqu.4; human. [P21964-1] DR AGR; HGNC:2228; -. DR CTD; 1312; -. DR DisGeNET; 1312; -. DR GeneCards; COMT; -. DR HGNC; HGNC:2228; COMT. DR HPA; ENSG00000093010; Low tissue specificity. DR MalaCards; COMT; -. DR MIM; 103780; phenotype. DR MIM; 116790; gene+phenotype. DR MIM; 181500; phenotype. DR neXtProt; NX_P21964; -. DR OpenTargets; ENSG00000093010; -. DR Orphanet; 567; 22q11.2 deletion syndrome. DR PharmGKB; PA117; -. DR VEuPathDB; HostDB:ENSG00000093010; -. DR eggNOG; KOG1663; Eukaryota. DR GeneTree; ENSGT00940000155317; -. DR HOGENOM; CLU_050461_5_0_1; -. DR InParanoid; P21964; -. DR OMA; WNELVLQ; -. DR OrthoDB; 4040098at2759; -. DR PhylomeDB; P21964; -. DR TreeFam; TF329140; -. DR BioCyc; MetaCyc:HS01791-MONOMER; -. DR BRENDA; 2.1.1.6; 2681. DR PathwayCommons; P21964; -. DR Reactome; R-HSA-156581; Methylation. DR Reactome; R-HSA-379397; Enzymatic degradation of dopamine by COMT. DR Reactome; R-HSA-379398; Enzymatic degradation of Dopamine by monoamine oxidase. DR Reactome; R-HSA-9679191; Potential therapeutics for SARS. DR SignaLink; P21964; -. DR SIGNOR; P21964; -. DR BioGRID-ORCS; 1312; 27 hits in 1169 CRISPR screens. DR ChiTaRS; COMT; human. DR EvolutionaryTrace; P21964; -. DR GeneWiki; Catechol-O-methyl_transferase; -. DR GenomeRNAi; 1312; -. DR Pharos; P21964; Tclin. DR PRO; PR:P21964; -. DR Proteomes; UP000005640; Chromosome 22. DR RNAct; P21964; Protein. DR Bgee; ENSG00000093010; Expressed in right adrenal gland cortex and 207 other cell types or tissues. DR ExpressionAtlas; P21964; baseline and differential. DR GO; GO:0030424; C:axon; IBA:GO_Central. DR GO; GO:0005829; C:cytosol; IDA:UniProtKB. DR GO; GO:0030425; C:dendrite; IBA:GO_Central. DR GO; GO:0070062; C:extracellular exosome; HDA:UniProtKB. DR GO; GO:0043231; C:intracellular membrane-bounded organelle; IDA:HPA. DR GO; GO:0016020; C:membrane; HDA:UniProtKB. DR GO; GO:0005886; C:plasma membrane; TAS:Reactome. DR GO; GO:0045202; C:synapse; IEA:GOC. DR GO; GO:0016206; F:catechol O-methyltransferase activity; IDA:UniProtKB. 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:0008168; F:methyltransferase activity; TAS:Reactome. DR GO; GO:0008171; F:O-methyltransferase activity; TAS:ProtInc. DR GO; GO:0102938; F:orcinol O-methyltransferase activity; IEA:UniProtKB-EC. DR GO; GO:0060840; P:artery development; IEA:Ensembl. DR GO; GO:0001662; P:behavioral fear response; IEA:Ensembl. DR GO; GO:0042424; P:catecholamine catabolic process; IDA:UniProtKB. DR GO; GO:0071314; P:cellular response to cocaine; IEA:Ensembl. DR GO; GO:0016036; P:cellular response to phosphate starvation; IEA:Ensembl. DR GO; GO:0021696; P:cerebellar cortex morphogenesis; IEA:Ensembl. DR GO; GO:0033344; P:cholesterol efflux; IEA:Ensembl. DR GO; GO:0050965; P:detection of temperature stimulus involved in sensory perception of pain; IEA:Ensembl. DR GO; GO:0032502; P:developmental process; IBA:GO_Central. DR GO; GO:0042420; P:dopamine catabolic process; TAS:Reactome. DR GO; GO:0042417; P:dopamine metabolic process; IBA:GO_Central. DR GO; GO:0014046; P:dopamine secretion; IEA:Ensembl. DR GO; GO:0035640; P:exploration behavior; IEA:Ensembl. DR GO; GO:0010467; P:gene expression; IEA:Ensembl. DR GO; GO:0032835; P:glomerulus development; IEA:Ensembl. DR GO; GO:0005977; P:glycogen metabolic process; IEA:Ensembl. DR GO; GO:0046959; P:habituation; IEA:Ensembl. DR GO; GO:0071626; P:mastication; IEA:Ensembl. DR GO; GO:0007613; P:memory; IEA:Ensembl. DR GO; GO:0032259; P:methylation; IDA:UniProtKB. DR GO; GO:0035264; P:multicellular organism growth; IEA:Ensembl. DR GO; GO:0042415; P:norepinephrine metabolic process; IEA:Ensembl. DR GO; GO:0048243; P:norepinephrine secretion; IEA:Ensembl. DR GO; GO:0006693; P:prostaglandin metabolic process; IEA:Ensembl. DR GO; GO:0097018; P:renal albumin absorption; IEA:Ensembl. DR GO; GO:0097205; P:renal filtration; IEA:Ensembl. DR GO; GO:0035812; P:renal sodium excretion; IEA:Ensembl. DR GO; GO:0002001; P:renin secretion into blood stream; IEA:Ensembl. DR GO; GO:0001975; P:response to amphetamine; IEA:Ensembl. DR GO; GO:1990776; P:response to angiotensin; IEA:Ensembl. DR GO; GO:0051412; P:response to corticosterone; IEA:Ensembl. DR GO; GO:0034097; P:response to cytokine; IEA:Ensembl. DR GO; GO:1903350; P:response to dopamine; IEA:Ensembl. DR GO; GO:0032094; P:response to food; IEA:Ensembl. DR GO; GO:0001666; P:response to hypoxia; IEA:Ensembl. DR GO; GO:0010035; P:response to inorganic substance; IEA:Ensembl. DR GO; GO:0006979; P:response to oxidative stress; IEA:Ensembl. DR GO; GO:0009636; P:response to toxic substance; IEA:Ensembl. DR GO; GO:0009611; P:response to wounding; IEA:Ensembl. DR GO; GO:0009410; P:response to xenobiotic stimulus; IEA:Ensembl. DR GO; GO:0001964; P:startle response; IEA:Ensembl. DR GO; GO:0001963; P:synaptic transmission, dopaminergic; IEA:Ensembl. DR GO; GO:0008542; P:visual learning; IEA:Ensembl. 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; P21964; HS. PE 1: Evidence at protein level; KW 3D-structure; Alternative initiation; Catecholamine metabolism; KW Cell membrane; Cytoplasm; Direct protein sequencing; Lipid metabolism; KW Magnesium; Membrane; Metal-binding; Methyltransferase; KW Neurotransmitter degradation; Phosphoprotein; Reference proteome; KW S-adenosyl-L-methionine; Schizophrenia; Signal-anchor; Transferase; KW Transmembrane; Transmembrane helix. FT CHAIN 1..271 FT /note="Catechol O-methyltransferase" FT /id="PRO_0000020971" FT TOPO_DOM 1..6 FT /note="Cytoplasmic" FT /evidence="ECO:0000255" FT TRANSMEM 7..26 FT /note="Helical; Signal-anchor for type II membrane protein" FT /evidence="ECO:0000255" FT TOPO_DOM 27..271 FT /note="Extracellular" FT /evidence="ECO:0000255" FT BINDING 92 FT /ligand="S-adenosyl-L-methionine" FT /ligand_id="ChEBI:CHEBI:59789" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01019, FT ECO:0000269|PubMed:18486144" FT BINDING 114 FT /ligand="S-adenosyl-L-methionine" FT /ligand_id="ChEBI:CHEBI:59789" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01019" FT BINDING 122 FT /ligand="S-adenosyl-L-methionine" FT /ligand_id="ChEBI:CHEBI:59789" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01019, FT ECO:0000269|PubMed:18486144" FT BINDING 140 FT /ligand="S-adenosyl-L-methionine" FT /ligand_id="ChEBI:CHEBI:59789" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01019, FT ECO:0000269|PubMed:18486144" FT BINDING 141 FT /ligand="S-adenosyl-L-methionine" FT /ligand_id="ChEBI:CHEBI:59789" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01019" FT BINDING 167..170 FT /ligand="S-adenosyl-L-methionine" FT /ligand_id="ChEBI:CHEBI:59789" FT BINDING 169 FT /ligand="S-adenosyl-L-methionine" FT /ligand_id="ChEBI:CHEBI:59789" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01019" FT BINDING 191 FT /ligand="Mg(2+)" FT /ligand_id="ChEBI:CHEBI:18420" FT /evidence="ECO:0000269|PubMed:18486144" FT BINDING 191 FT /ligand="S-adenosyl-L-methionine" FT /ligand_id="ChEBI:CHEBI:59789" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01019, FT ECO:0000269|PubMed:18486144" FT BINDING 194 FT /ligand="substrate" FT BINDING 219 FT /ligand="Mg(2+)" FT /ligand_id="ChEBI:CHEBI:18420" FT /evidence="ECO:0000269|PubMed:18486144" FT BINDING 220 FT /ligand="Mg(2+)" FT /ligand_id="ChEBI:CHEBI:18420" FT /evidence="ECO:0000269|PubMed:18486144" FT BINDING 220 FT /ligand="substrate" FT BINDING 249 FT /ligand="substrate" FT MOD_RES 267 FT /note="Phosphoserine" FT /evidence="ECO:0000250|UniProtKB:P22734" FT VAR_SEQ 1..50 FT /note="Missing (in isoform Soluble)" FT /evidence="ECO:0000305" FT /id="VSP_018778" FT VARIANT 34 FT /note="C -> S (in dbSNP:rs6270)" FT /evidence="ECO:0000269|PubMed:10391209, FT ECO:0000269|PubMed:1847521" FT /id="VAR_013925" FT VARIANT 72 FT /note="A -> S (correlated with reduced enzyme activity; FT associated with increased risk for schizophrenia; FT dbSNP:rs6267)" FT /evidence="ECO:0000269|PubMed:10391209, FT ECO:0000269|PubMed:15645182, ECO:0000269|Ref.8" FT /id="VAR_013926" FT VARIANT 102 FT /note="A -> T (in dbSNP:rs5031015)" FT /id="VAR_020274" FT VARIANT 146 FT /note="A -> V (in dbSNP:rs4986871)" FT /id="VAR_020275" FT VARIANT 158 FT /note="V -> M (in allele COMT*2; associated with low enzyme FT activity and thermolability; may increase the tendency to FT develop high blood pressure and abdominal obesity; FT dbSNP:rs4680)" FT /evidence="ECO:0000269|PubMed:11559542, FT ECO:0000269|PubMed:15461802, ECO:0000269|PubMed:18442637, FT ECO:0000269|PubMed:18474266, ECO:0000269|PubMed:8807664, FT ECO:0000269|Ref.10, ECO:0000269|Ref.8" FT /id="VAR_005139" FT CONFLICT 245 FT /note="Q -> N (in Ref. 13; AA sequence)" FT /evidence="ECO:0000305" FT HELIX 55..66 FT /evidence="ECO:0007829|PDB:3BWY" FT HELIX 72..85 FT /evidence="ECO:0007829|PDB:3BWY" FT HELIX 93..107 FT /evidence="ECO:0007829|PDB:3BWY" FT STRAND 110..115 FT /evidence="ECO:0007829|PDB:3BWY" FT STRAND 118..120 FT /evidence="ECO:0007829|PDB:4PYJ" FT HELIX 121..127 FT /evidence="ECO:0007829|PDB:3BWY" FT STRAND 135..141 FT /evidence="ECO:0007829|PDB:3BWY" FT HELIX 143..155 FT /evidence="ECO:0007829|PDB:3BWY" FT HELIX 159..161 FT /evidence="ECO:0007829|PDB:3BWY" FT STRAND 162..167 FT /evidence="ECO:0007829|PDB:3BWY" FT HELIX 169..172 FT /evidence="ECO:0007829|PDB:3BWY" FT HELIX 173..175 FT /evidence="ECO:0007829|PDB:3BWY" FT HELIX 176..180 FT /evidence="ECO:0007829|PDB:3BWY" FT STRAND 185..190 FT /evidence="ECO:0007829|PDB:3BWY" FT HELIX 194..196 FT /evidence="ECO:0007829|PDB:3BWY" FT HELIX 197..206 FT /evidence="ECO:0007829|PDB:3BWY" FT STRAND 210..219 FT /evidence="ECO:0007829|PDB:3BWY" FT HELIX 221..225 FT /evidence="ECO:0007829|PDB:3BWY" FT HELIX 227..235 FT /evidence="ECO:0007829|PDB:3BWY" FT STRAND 239..247 FT /evidence="ECO:0007829|PDB:3BWY" FT STRAND 251..262 FT /evidence="ECO:0007829|PDB:3BWY" SQ SEQUENCE 271 AA; 30037 MW; D2547A1C399AC758 CRC64; MPEAPPLLLA AVLLGLVLLV VLLLLLRHWG WGLCLIGWNE FILQPIHNLL MGDTKEQRIL NHVLQHAEPG NAQSVLEAID TYCEQKEWAM NVGDKKGKIV DAVIQEHQPS VLLELGAYCG YSAVRMARLL SPGARLITIE INPDCAAITQ RMVDFAGVKD KVTLVVGASQ DIIPQLKKKY DVDTLDMVFL DHWKDRYLPD TLLLEECGLL RKGTVLLADN VICPGAPDFL AHVRGSSCFE CTHYQSFLEY REVVDGLEKA IYKGPGSEAG P //