ID COMT_RAT Reviewed; 264 AA. AC P22734; DT 01-AUG-1991, integrated into UniProtKB/Swiss-Prot. DT 01-MAY-1992, sequence version 2. DT 27-MAR-2024, entry version 214. DE RecName: Full=Catechol O-methyltransferase {ECO:0000305}; DE EC=2.1.1.6 {ECO:0000305|PubMed:16618795}; GN Name=Comt {ECO:0000312|RGD:2379}; OS Rattus norvegicus (Rat). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae; OC Murinae; Rattus. OX NCBI_TaxID=10116; RN [1] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND ALTERNATIVE INITIATION. RC TISSUE=Liver; RX PubMed=8280056; DOI=10.1042/bj2960595; RA Tenhunen J., Ulmanen I.; RT "Production of rat soluble and membrane-bound catechol O-methyltransferase RT forms from bifunctional mRNAs."; RL Biochem. J. 296:595-600(1993). RN [2] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM MEMBRANE-BOUND). RC TISSUE=Heart; RX PubMed=15489334; DOI=10.1101/gr.2596504; RG The MGC Project Team; RT "The status, quality, and expansion of the NIH full-length cDNA project: RT the Mammalian Gene Collection (MGC)."; RL Genome Res. 14:2121-2127(2004). RN [3] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA / MRNA] OF 11-264. RX PubMed=2227437; DOI=10.1016/0378-1119(90)90231-f; RA Salminen M., Lundstroem K., Tilgmann C., Savolainen R., Kalkkinen N., RA Ulmanen I.; RT "Molecular cloning and characterization of rat liver catechol-O- RT methyltransferase."; RL Gene 93:241-247(1990). RN [4] RP NUCLEOTIDE SEQUENCE [MRNA] OF 1-10, CHARACTERIZATION OF THE TWO FORMS, AND RP SUBCELLULAR LOCATION. 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 [5] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-259; SER-260 AND SER-264, AND RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RX PubMed=22673903; DOI=10.1038/ncomms1871; RA Lundby A., Secher A., Lage K., Nordsborg N.B., Dmytriyev A., Lundby C., RA Olsen J.V.; RT "Quantitative maps of protein phosphorylation sites across 14 different rat RT organs and tissues."; RL Nat. Commun. 3:876-876(2012). RN [6] RP X-RAY CRYSTALLOGRAPHY (2.0 ANGSTROMS) OF 44-264. RX PubMed=8127373; DOI=10.1038/368354a0; RA Vidgren J., Svensson L.A., Liljas A.; RT "Crystal structure of catechol O-methyltransferase."; RL Nature 368:354-358(1994). RN [7] RP X-RAY CRYSTALLOGRAPHY (2.63 ANGSTROMS) OF 44-264 IN COMPLEX WITH SUBSTRATE RP ANALOG. RX PubMed=10785817; RX DOI=10.1002/(sici)1521-3765(20000317)6:6<971::aid-chem971>3.0.co;2-0; RA Masjost B., Ballmer P., Borroni E., Zuercher G., Winkler F.K., RA Jakob-Roetne R., Diederich F.; RT "Structure-based design, synthesis, and in vitro evaluation of bisubstrate RT inhibitors for catechol O-methyltransferase (COMT)."; RL Chemistry 6:971-982(2000). RN [8] {ECO:0007744|PDB:1H1D} RP X-RAY CRYSTALLOGRAPHY (2.0 ANGSTROMS) OF 44-264 IN COMPLEX WITH RP S-ADENOSYL-L-METHIONINE AND SUBSTRATE ANALOG, AND FUNCTION. RX PubMed=12237326; DOI=10.1124/mol.62.4.795; RA Bonifacio M.J., Archer M., Rodrigues M.L., Matias P.M., Learmonth D.A., RA Carrondo M.A., Soares-da-Silva P.; RT "Kinetics and crystal structure of catechol-O-methyltransferase complex RT with co-substrate and a novel inhibitor with potential therapeutic RT application."; RL Mol. Pharmacol. 62:795-805(2002). RN [9] {ECO:0007744|PDB:2CL5} RP X-RAY CRYSTALLOGRAPHY (1.6 ANGSTROMS) OF 44-264 IN COMPLEX WITH SUBSTRATE RP ANALOG, FUNCTION, AND BIOPHYSICOCHEMICAL PROPERTIES. RX PubMed=16618795; DOI=10.1124/mol.106.023119; RA Palma P.N., Rodrigues M.L., Archer M., Bonifacio M.J., Loureiro A.I., RA Learmonth D.A., Carrondo M.A., Soares-da-Silva P.; RT "Comparative study of ortho- and meta-nitrated inhibitors of catechol-O- RT methyltransferase: interactions with the active site and regioselectivity RT of O-methylation."; RL Mol. Pharmacol. 70:143-153(2006). 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:12237326, CC ECO:0000269|PubMed:16618795}. 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 Note=Binds 1 Mg(2+) ion per subunit. {ECO:0000269|PubMed:16618795}; CC -!- BIOPHYSICOCHEMICAL PROPERTIES: CC Kinetic parameters: CC KM=30 uM for S-adenosyl-L-methionine {ECO:0000269|PubMed:16618795}; CC Vmax=377 nmol/h/mg enzyme {ECO:0000269|PubMed:16618795}; CC -!- SUBCELLULAR LOCATION: [Isoform Soluble]: Cytoplasm CC {ECO:0000269|PubMed:1765063}. CC -!- SUBCELLULAR LOCATION: [Isoform Membrane-bound]: Cell membrane CC {ECO:0000269|PubMed:1765063}; Single-pass type II membrane protein CC {ECO:0000255}; Extracellular side {ECO:0000305|PubMed:1765063}. CC -!- ALTERNATIVE PRODUCTS: CC Event=Alternative initiation; Named isoforms=2; CC Name=Membrane-bound; Synonyms=MB-COMT; CC IsoId=P22734-1; Sequence=Displayed; CC Name=Soluble; Synonyms=S-COMT; CC IsoId=P22734-2; Sequence=VSP_018780; CC -!- PTM: The N-terminus is blocked. 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=AAA40881.1; Type=Erroneous initiation; Note=Truncated N-terminus.; Evidence={ECO:0000305}; CC Sequence=AAA40882.1; Type=Erroneous initiation; Note=Truncated N-terminus.; Evidence={ECO:0000305}; 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; Z12651; CAA78276.1; -; Genomic_DNA. DR EMBL; M60754; AAA40882.1; ALT_INIT; Genomic_DNA. DR EMBL; BC081850; AAH81850.1; -; mRNA. DR EMBL; M60753; AAA40881.1; ALT_INIT; mRNA. DR PIR; S22090; S22090. DR RefSeq; NP_036663.1; NM_012531.2. [P22734-1] DR PDB; 1H1D; X-ray; 2.00 A; A=44-264. DR PDB; 1JR4; X-ray; 2.63 A; A=44-264. DR PDB; 1VID; X-ray; 2.00 A; A=44-264. DR PDB; 2CL5; X-ray; 1.60 A; A/B=44-264. DR PDB; 2ZLB; X-ray; 2.20 A; A=44-264. DR PDB; 2ZTH; X-ray; 2.60 A; A=44-264. DR PDB; 2ZVJ; X-ray; 2.30 A; A=44-264. DR PDB; 3A7D; X-ray; 2.40 A; A=44-264. DR PDB; 3HVH; X-ray; 1.30 A; A=44-264. DR PDB; 3HVI; X-ray; 1.20 A; A=44-264. DR PDB; 3HVJ; X-ray; 1.79 A; A/B=44-264. DR PDB; 3HVK; X-ray; 1.30 A; A=44-264. DR PDB; 3NW9; X-ray; 1.65 A; A=44-264. DR PDB; 3NWB; X-ray; 1.30 A; A=44-264. DR PDB; 3NWE; X-ray; 1.50 A; A=44-264. DR PDB; 3OE4; X-ray; 1.49 A; A=44-264. DR PDB; 3OE5; X-ray; 1.52 A; A=44-264. DR PDB; 3OZR; X-ray; 1.73 A; A=44-264. DR PDB; 3OZS; X-ray; 1.44 A; A=44-264. DR PDB; 3OZT; X-ray; 1.48 A; A=44-264. DR PDB; 3R6T; X-ray; 1.20 A; A=44-264. DR PDB; 3S68; X-ray; 1.85 A; A=44-264. DR PDB; 3U81; X-ray; 1.13 A; A=44-264. DR PDB; 4P7G; X-ray; 2.58 A; A/B/C/D=44-264. DR PDB; 4P7J; X-ray; 1.45 A; A=44-264. DR PDB; 4P7K; X-ray; 1.22 A; A=44-264. DR PDB; 4PYL; X-ray; 2.20 A; A=44-264. DR PDB; 4PYM; X-ray; 1.19 A; A=44-264. DR PDB; 4PYN; X-ray; 1.20 A; A=44-264. DR PDB; 4PYO; X-ray; 2.10 A; A/B=44-264. DR PDB; 4PYQ; X-ray; 1.39 A; A/B=44-264. DR PDB; 5FHQ; X-ray; 1.63 A; A=46-258. DR PDB; 5FHR; X-ray; 1.63 A; A/B=46-258. DR PDB; 5K01; X-ray; 1.38 A; A=46-258. DR PDB; 5K03; X-ray; 1.81 A; A=46-259. DR PDB; 5K05; X-ray; 2.14 A; A/B=46-259. DR PDB; 5K09; X-ray; 2.70 A; A/B/C/D/E/F/G/H/I/J/K/L/M/N/O/P/Q/R/S/T/U/V/W/X=45-260. DR PDB; 5K0B; X-ray; 2.36 A; A/B/C/D/E/F/G/H=45-261. DR PDB; 5K0C; X-ray; 1.95 A; A/B=45-259. DR PDB; 5K0E; X-ray; 2.30 A; A=45-259. DR PDB; 5K0F; X-ray; 1.81 A; A/B=45-263. DR PDB; 5K0G; X-ray; 1.89 A; A/B=45-264. DR PDB; 5K0J; X-ray; 1.94 A; A/B=45-264. DR PDB; 5K0L; X-ray; 2.02 A; A/B/C/D=45-263. DR PDB; 5K0N; X-ray; 1.99 A; A/B/C/D=45-264. DR PDB; 5LQA; X-ray; 1.20 A; A=46-258. DR PDB; 5LQC; X-ray; 1.90 A; A=44-264. DR PDB; 5LQJ; X-ray; 2.41 A; A/B/C/D=44-264. DR PDB; 5LQK; X-ray; 2.24 A; A=44-264. DR PDB; 5LQN; X-ray; 1.72 A; A=44-264. DR PDB; 5LQR; X-ray; 1.50 A; A=44-264. DR PDB; 5LQU; X-ray; 1.80 A; A/B=44-264. DR PDB; 5LR6; X-ray; 2.30 A; A/B/C/D=44-264. DR PDB; 5P8W; X-ray; 2.03 A; A/B/C=44-264. DR PDB; 5P8X; X-ray; 1.31 A; A=44-264. DR PDB; 5P8Y; X-ray; 1.42 A; A=44-264. DR PDB; 5P8Z; X-ray; 1.42 A; A=44-264. DR PDB; 5P90; X-ray; 1.24 A; A=44-264. DR PDB; 5P91; X-ray; 1.20 A; A=44-264. DR PDB; 5P92; X-ray; 1.61 A; A=44-264. DR PDB; 5P93; X-ray; 1.24 A; A=44-264. DR PDB; 5P94; X-ray; 1.20 A; A=44-264. DR PDB; 5P95; X-ray; 1.30 A; A=44-264. DR PDB; 5P96; X-ray; 1.40 A; A=44-264. DR PDB; 5P97; X-ray; 1.30 A; A=44-264. DR PDB; 5P98; X-ray; 1.20 A; A=44-264. DR PDB; 5P99; X-ray; 1.20 A; A=44-264. DR PDB; 5P9A; X-ray; 1.91 A; A=44-264. DR PDB; 5P9B; X-ray; 1.45 A; A=44-264. DR PDB; 5P9C; X-ray; 1.70 A; A=44-264. DR PDB; 5P9D; X-ray; 1.42 A; A=44-264. DR PDB; 5P9E; X-ray; 1.50 A; A=44-264. DR PDB; 5P9N; X-ray; 1.17 A; A=44-264. DR PDB; 5P9O; X-ray; 1.10 A; A=44-264. DR PDB; 5P9P; X-ray; 1.12 A; A=44-264. DR PDB; 5P9Q; X-ray; 1.63 A; A=44-264. DR PDB; 5P9R; X-ray; 1.70 A; A/B=44-264. DR PDB; 5P9S; X-ray; 2.30 A; A=44-264. DR PDB; 5P9T; X-ray; 1.24 A; A=44-264. DR PDB; 5P9U; X-ray; 1.42 A; A=44-264. DR PDB; 5P9V; X-ray; 1.04 A; A=44-264. DR PDB; 5P9W; X-ray; 1.43 A; A=44-264. DR PDB; 5P9X; X-ray; 1.12 A; A=44-264. DR PDB; 5P9Y; X-ray; 1.20 A; A=44-264. DR PDB; 5P9Z; X-ray; 1.60 A; A=44-264. DR PDB; 5PA0; X-ray; 1.26 A; A=44-264. DR PDB; 5PA1; X-ray; 1.24 A; A=44-264. DR PDB; 5PA2; X-ray; 1.12 A; A=44-264. DR PDB; 5PA3; X-ray; 1.60 A; A=44-264. DR PDB; 5PA4; X-ray; 1.99 A; A=44-264. DR PDB; 5PA5; X-ray; 1.63 A; A=44-264. DR PDB; 5PA6; X-ray; 1.29 A; A=44-264. DR PDB; 5PA7; X-ray; 2.12 A; A/B=44-264. DR PDB; 6GY1; X-ray; 2.10 A; A=44-264. DR PDB; 6LFE; X-ray; 1.60 A; A=44-264. DR PDB; 7UD6; X-ray; 2.59 A; A=47-258. DR PDB; 7XGI; X-ray; 2.00 A; A=44-264. DR PDB; 7XJB; X-ray; 2.60 A; A/B/C/D=44-264. DR PDBsum; 1H1D; -. DR PDBsum; 1JR4; -. DR PDBsum; 1VID; -. DR PDBsum; 2CL5; -. DR PDBsum; 2ZLB; -. DR PDBsum; 2ZTH; -. DR PDBsum; 2ZVJ; -. DR PDBsum; 3A7D; -. DR PDBsum; 3HVH; -. DR PDBsum; 3HVI; -. DR PDBsum; 3HVJ; -. DR PDBsum; 3HVK; -. DR PDBsum; 3NW9; -. DR PDBsum; 3NWB; -. DR PDBsum; 3NWE; -. DR PDBsum; 3OE4; -. DR PDBsum; 3OE5; -. DR PDBsum; 3OZR; -. DR PDBsum; 3OZS; -. DR PDBsum; 3OZT; -. DR PDBsum; 3R6T; -. DR PDBsum; 3S68; -. DR PDBsum; 3U81; -. DR PDBsum; 4P7G; -. DR PDBsum; 4P7J; -. DR PDBsum; 4P7K; -. DR PDBsum; 4PYL; -. DR PDBsum; 4PYM; -. DR PDBsum; 4PYN; -. DR PDBsum; 4PYO; -. DR PDBsum; 4PYQ; -. DR PDBsum; 5FHQ; -. DR PDBsum; 5FHR; -. DR PDBsum; 5K01; -. DR PDBsum; 5K03; -. DR PDBsum; 5K05; -. DR PDBsum; 5K09; -. DR PDBsum; 5K0B; -. DR PDBsum; 5K0C; -. DR PDBsum; 5K0E; -. DR PDBsum; 5K0F; -. DR PDBsum; 5K0G; -. DR PDBsum; 5K0J; -. DR PDBsum; 5K0L; -. DR PDBsum; 5K0N; -. DR PDBsum; 5LQA; -. DR PDBsum; 5LQC; -. DR PDBsum; 5LQJ; -. DR PDBsum; 5LQK; -. DR PDBsum; 5LQN; -. DR PDBsum; 5LQR; -. DR PDBsum; 5LQU; -. DR PDBsum; 5LR6; -. DR PDBsum; 5P8W; -. DR PDBsum; 5P8X; -. DR PDBsum; 5P8Y; -. DR PDBsum; 5P8Z; -. DR PDBsum; 5P90; -. DR PDBsum; 5P91; -. DR PDBsum; 5P92; -. DR PDBsum; 5P93; -. DR PDBsum; 5P94; -. DR PDBsum; 5P95; -. DR PDBsum; 5P96; -. DR PDBsum; 5P97; -. DR PDBsum; 5P98; -. DR PDBsum; 5P99; -. DR PDBsum; 5P9A; -. DR PDBsum; 5P9B; -. DR PDBsum; 5P9C; -. DR PDBsum; 5P9D; -. DR PDBsum; 5P9E; -. DR PDBsum; 5P9N; -. DR PDBsum; 5P9O; -. DR PDBsum; 5P9P; -. DR PDBsum; 5P9Q; -. DR PDBsum; 5P9R; -. DR PDBsum; 5P9S; -. DR PDBsum; 5P9T; -. DR PDBsum; 5P9U; -. DR PDBsum; 5P9V; -. DR PDBsum; 5P9W; -. DR PDBsum; 5P9X; -. DR PDBsum; 5P9Y; -. DR PDBsum; 5P9Z; -. DR PDBsum; 5PA0; -. DR PDBsum; 5PA1; -. DR PDBsum; 5PA2; -. DR PDBsum; 5PA3; -. DR PDBsum; 5PA4; -. DR PDBsum; 5PA5; -. DR PDBsum; 5PA6; -. DR PDBsum; 5PA7; -. DR PDBsum; 6GY1; -. DR PDBsum; 6LFE; -. DR PDBsum; 7UD6; -. DR PDBsum; 7XGI; -. DR PDBsum; 7XJB; -. DR AlphaFoldDB; P22734; -. DR SMR; P22734; -. DR STRING; 10116.ENSRNOP00000043148; -. DR BindingDB; P22734; -. DR ChEMBL; CHEMBL2372; -. DR DrugCentral; P22734; -. DR GuidetoPHARMACOLOGY; 2472; -. DR iPTMnet; P22734; -. DR PhosphoSitePlus; P22734; -. DR jPOST; P22734; -. DR PaxDb; 10116-ENSRNOP00000043148; -. DR Ensembl; ENSRNOT00000050269.6; ENSRNOP00000043148.4; ENSRNOG00000001889.8. [P22734-2] DR Ensembl; ENSRNOT00055005465; ENSRNOP00055004071; ENSRNOG00055003518. [P22734-1] DR Ensembl; ENSRNOT00060021520; ENSRNOP00060017008; ENSRNOG00060012669. [P22734-1] DR Ensembl; ENSRNOT00065013046; ENSRNOP00065009626; ENSRNOG00065008231. [P22734-1] DR GeneID; 24267; -. DR KEGG; rno:24267; -. DR AGR; RGD:2379; -. DR CTD; 1312; -. DR RGD; 2379; Comt. DR VEuPathDB; HostDB:ENSRNOG00000001889; -. DR eggNOG; KOG1663; Eukaryota. DR GeneTree; ENSGT00940000155317; -. DR HOGENOM; CLU_050461_5_0_1; -. DR InParanoid; P22734; -. DR OrthoDB; 4040098at2759; -. DR PhylomeDB; P22734; -. DR TreeFam; TF329140; -. DR BioCyc; MetaCyc:MONOMER-15100; -. DR BRENDA; 2.1.1.6; 5301. DR Reactome; R-RNO-156581; Methylation. DR Reactome; R-RNO-379397; Enzymatic degradation of dopamine by COMT. DR Reactome; R-RNO-379398; Enzymatic degradation of Dopamine by monoamine oxidase. DR SABIO-RK; P22734; -. DR EvolutionaryTrace; P22734; -. DR PRO; PR:P22734; -. DR Proteomes; UP000002494; Chromosome 11. DR Bgee; ENSRNOG00000001889; Expressed in liver and 19 other cell types or tissues. DR ExpressionAtlas; P22734; baseline and differential. DR GO; GO:0030424; C:axon; IDA:RGD. DR GO; GO:0044297; C:cell body; IDA:RGD. DR GO; GO:0005829; C:cytosol; ISO:RGD. DR GO; GO:0030425; C:dendrite; IDA:RGD. DR GO; GO:0043197; C:dendritic spine; IDA:RGD. DR GO; GO:0098978; C:glutamatergic synapse; IDA:SynGO. DR GO; GO:0016020; C:membrane; IBA:GO_Central. DR GO; GO:0098794; C:postsynapse; IDA:SynGO. DR GO; GO:0045211; C:postsynaptic membrane; IDA:RGD. DR GO; GO:0031982; C:vesicle; ISO:RGD. DR GO; GO:0016206; F:catechol O-methyltransferase activity; IDA:RGD. 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; ISO:RGD. DR GO; GO:0001662; P:behavioral fear response; ISO:RGD. DR GO; GO:0009712; P:catechol-containing compound metabolic process; ISO:RGD. DR GO; GO:0042424; P:catecholamine catabolic process; ISS:UniProtKB. DR GO; GO:0006584; P:catecholamine metabolic process; ISO:RGD. DR GO; GO:0071314; P:cellular response to cocaine; ISO:RGD. DR GO; GO:0016036; P:cellular response to phosphate starvation; ISO:RGD. DR GO; GO:0021696; P:cerebellar cortex morphogenesis; ISO:RGD. DR GO; GO:0033344; P:cholesterol efflux; ISO:RGD. DR GO; GO:0050890; P:cognition; ISO:RGD. DR GO; GO:0050965; P:detection of temperature stimulus involved in sensory perception of pain; ISO:RGD. DR GO; GO:0032502; P:developmental process; IBA:GO_Central. DR GO; GO:0042420; P:dopamine catabolic process; ISO:RGD. DR GO; GO:0042417; P:dopamine metabolic process; ISO:RGD. DR GO; GO:0014046; P:dopamine secretion; ISO:RGD. DR GO; GO:0008210; P:estrogen metabolic process; IMP:RGD. DR GO; GO:0035640; P:exploration behavior; ISO:RGD. DR GO; GO:0042596; P:fear response; ISO:RGD. DR GO; GO:0007565; P:female pregnancy; IMP:RGD. DR GO; GO:0010467; P:gene expression; ISO:RGD. DR GO; GO:0032835; P:glomerulus development; ISO:RGD. DR GO; GO:0005977; P:glycogen metabolic process; ISO:RGD. DR GO; GO:0046959; P:habituation; ISO:RGD. DR GO; GO:0001822; P:kidney development; ISO:RGD. DR GO; GO:0007612; P:learning; IMP:RGD. DR GO; GO:0007611; P:learning or memory; ISO:RGD. DR GO; GO:0071626; P:mastication; ISO:RGD. DR GO; GO:0007613; P:memory; ISO:RGD. DR GO; GO:0032259; P:methylation; ISS:UniProtKB. DR GO; GO:0035264; P:multicellular organism growth; ISO:RGD. DR GO; GO:0048609; P:multicellular organismal reproductive process; IMP:RGD. DR GO; GO:0033555; P:multicellular organismal response to stress; ISO:RGD. DR GO; GO:0045963; P:negative regulation of dopamine metabolic process; IMP:RGD. DR GO; GO:0048662; P:negative regulation of smooth muscle cell proliferation; IMP:RGD. DR GO; GO:0042415; P:norepinephrine metabolic process; ISO:RGD. DR GO; GO:0048243; P:norepinephrine secretion; ISO:RGD. DR GO; GO:0050668; P:positive regulation of homocysteine metabolic process; IMP:RGD. DR GO; GO:0006693; P:prostaglandin metabolic process; ISO:RGD. DR GO; GO:0008217; P:regulation of blood pressure; ISO:RGD. DR GO; GO:0097018; P:renal albumin absorption; ISO:RGD. DR GO; GO:0097205; P:renal filtration; ISO:RGD. DR GO; GO:0035812; P:renal sodium excretion; ISO:RGD. DR GO; GO:0002001; P:renin secretion into blood stream; ISO:RGD. DR GO; GO:0001975; P:response to amphetamine; ISO:RGD. DR GO; GO:1990776; P:response to angiotensin; ISO:RGD. DR GO; GO:0051412; P:response to corticosterone; ISO:RGD. DR GO; GO:0034097; P:response to cytokine; ISO:RGD. DR GO; GO:1903350; P:response to dopamine; ISO:RGD. DR GO; GO:0043627; P:response to estrogen; IEP:RGD. DR GO; GO:0032094; P:response to food; ISO:RGD. DR GO; GO:0001666; P:response to hypoxia; ISO:RGD. DR GO; GO:0010035; P:response to inorganic substance; ISO:RGD. DR GO; GO:0032496; P:response to lipopolysaccharide; IEP:RGD. DR GO; GO:0014070; P:response to organic cyclic compound; IEP:RGD. DR GO; GO:0010033; P:response to organic substance; ISO:RGD. DR GO; GO:0006979; P:response to oxidative stress; ISO:RGD. DR GO; GO:0048265; P:response to pain; IMP:RGD. DR GO; GO:1902074; P:response to salt; ISO:RGD. DR GO; GO:0009266; P:response to temperature stimulus; ISO:RGD. DR GO; GO:0009636; P:response to toxic substance; ISO:RGD. DR GO; GO:0009611; P:response to wounding; ISO:RGD. DR GO; GO:0009410; P:response to xenobiotic stimulus; IEP:RGD. DR GO; GO:0046498; P:S-adenosylhomocysteine metabolic process; TAS:RGD. DR GO; GO:0046500; P:S-adenosylmethionine metabolic process; TAS:RGD. DR GO; GO:0007614; P:short-term memory; IMP:RGD. DR GO; GO:0001964; P:startle response; ISO:RGD. DR GO; GO:0001963; P:synaptic transmission, dopaminergic; ISO:RGD. DR GO; GO:0008542; P:visual learning; ISO:RGD. 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; P22734; RN. 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..264 FT /note="Catechol O-methyltransferase" FT /id="PRO_0000020975" 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..264 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 ECO:0000269|PubMed:12237326" 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 ECO:0000269|PubMed:12237326" FT BINDING 133 FT /ligand="S-adenosyl-L-methionine" FT /ligand_id="ChEBI:CHEBI:59789" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01019, FT ECO:0000269|PubMed:12237326" 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 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 BINDING 184 FT /ligand="S-adenosyl-L-methionine" FT /ligand_id="ChEBI:CHEBI:59789" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01019, FT ECO:0000269|PubMed:12237326" FT BINDING 187 FT /ligand="substrate" FT BINDING 212 FT /ligand="Mg(2+)" FT /ligand_id="ChEBI:CHEBI:18420" FT BINDING 213 FT /ligand="Mg(2+)" FT /ligand_id="ChEBI:CHEBI:18420" FT BINDING 213 FT /ligand="substrate" FT BINDING 242 FT /ligand="substrate" FT MOD_RES 259 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:22673903" FT MOD_RES 260 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:22673903" FT MOD_RES 264 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:22673903" FT VAR_SEQ 1..43 FT /note="Missing (in isoform Soluble)" FT /evidence="ECO:0000305" FT /id="VSP_018780" FT HELIX 48..59 FT /evidence="ECO:0007829|PDB:5P9V" FT HELIX 65..78 FT /evidence="ECO:0007829|PDB:5P9V" FT HELIX 82..84 FT /evidence="ECO:0007829|PDB:3U81" FT HELIX 86..100 FT /evidence="ECO:0007829|PDB:5P9V" FT STRAND 103..108 FT /evidence="ECO:0007829|PDB:5P9V" FT STRAND 111..113 FT /evidence="ECO:0007829|PDB:4PYM" FT HELIX 114..120 FT /evidence="ECO:0007829|PDB:5P9V" FT STRAND 128..134 FT /evidence="ECO:0007829|PDB:5P9V" FT HELIX 136..149 FT /evidence="ECO:0007829|PDB:5P9V" FT TURN 152..154 FT /evidence="ECO:0007829|PDB:5P9V" FT STRAND 155..160 FT /evidence="ECO:0007829|PDB:5P9V" FT HELIX 162..165 FT /evidence="ECO:0007829|PDB:5P9V" FT HELIX 166..168 FT /evidence="ECO:0007829|PDB:5P9V" FT TURN 169..173 FT /evidence="ECO:0007829|PDB:5P9V" FT STRAND 179..183 FT /evidence="ECO:0007829|PDB:5P9V" FT HELIX 187..189 FT /evidence="ECO:0007829|PDB:5P9V" FT HELIX 190..199 FT /evidence="ECO:0007829|PDB:5P9V" FT STRAND 208..212 FT /evidence="ECO:0007829|PDB:5P9V" FT HELIX 214..218 FT /evidence="ECO:0007829|PDB:5P9V" FT HELIX 220..228 FT /evidence="ECO:0007829|PDB:5P9V" FT STRAND 232..240 FT /evidence="ECO:0007829|PDB:5P9V" FT STRAND 244..255 FT /evidence="ECO:0007829|PDB:5P9V" SQ SEQUENCE 264 AA; 29597 MW; F535DFF49C062854 CRC64; MPLAAVSLGL LLLALLLLLR HLGWGLVTIF WFEYVLQPVH NLIMGDTKEQ RILRYVQQNA KPGDPQSVLE AIDTYCTQKE WAMNVGDAKG QIMDAVIREY SPSLVLELGA YCGYSAVRMA RLLQPGARLL TMEMNPDYAA ITQQMLNFAG LQDKVTILNG ASQDLIPQLK KKYDVDTLDM VFLDHWKDRY LPDTLLLEKC GLLRKGTVLL ADNVIVPGTP DFLAYVRGSS SFECTHYSSY LEYMKVVDGL EKAIYQGPSS PDKS //