COMT_HUMAN
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 03-AUG-2022, entry version 234.
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, 2-
CC 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; 153.
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; P21964; -.
DR PeptideAtlas; P21964; -.
DR PRIDE; P21964; -.
DR ProteomicsDB; 53945; -. [P21964-1]
DR ProteomicsDB; 53946; -. [P21964-2]
DR TopDownProteomics; P21964-1; -. [P21964-1]
DR TopDownProteomics; P21964-2; -. [P21964-2]
DR Antibodypedia; 213; 640 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 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 Orphanet; 240863; Prediction of cisplatin toxicity.
DR Orphanet; 284121; Prediction of toxicity or absent response to clozapine.
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; 1274244at2759; -.
DR PhylomeDB; P21964; -.
DR TreeFam; TF329140; -.
DR BioCyc; MetaCyc:HS01791-MON; -.
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; 24 hits in 1083 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 205 other tissues.
DR ExpressionAtlas; P21964; baseline and differential.
DR Genevisible; P21964; HS.
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:0016021; C:integral component of membrane; IEA:UniProtKB-KW.
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: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; IBA:GO_Central.
DR GO; GO:0102938; F:orcinol O-methyltransferase activity; IEA:UniProtKB-EC.
DR GO; GO:0042424; P:catecholamine catabolic process; IDA:UniProtKB.
DR GO; GO:0016036; P:cellular response to phosphate starvation; 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:0006629; P:lipid metabolic process; IEA:UniProtKB-KW.
DR GO; GO:0032259; P:methylation; IDA:UniProtKB.
DR GO; GO:0042135; P:neurotransmitter catabolic process; IEA:UniProtKB-KW.
DR Gene3D; 3.40.50.150; -; 1.
DR InterPro; IPR017128; Catechol_O-MeTrfase_euk.
DR InterPro; IPR029063; SAM-dependent_MTases_sf.
DR InterPro; IPR002935; SAM_O-MeTrfase.
DR Pfam; PF01596; Methyltransf_3; 1.
DR PIRSF; PIRSF037177; Catechol_O-mtfrase_euk; 1.
DR SUPFAM; SSF53335; SSF53335; 1.
DR PROSITE; PS51682; SAM_OMT_I; 1.
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
