COMT_RAT
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 03-AUG-2022, entry version 205.
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};
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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 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 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; P22734; -.
DR PRIDE; P22734; -.
DR Ensembl; ENSRNOT00000050269; ENSRNOP00000043148; ENSRNOG00000001889. [P22734-2]
DR GeneID; 24267; -.
DR KEGG; rno:24267; -.
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 OMA; WNELVLQ; -.
DR OrthoDB; 1274244at2759; -.
DR PhylomeDB; P22734; -.
DR TreeFam; TF329140; -.
DR BioCyc; MetaCyc:MON-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 tissues.
DR ExpressionAtlas; P22734; baseline and differential.
DR Genevisible; P22734; RN.
DR GO; GO:0030424; C:axon; IDA:RGD.
DR GO; GO:0044297; C:cell body; IDA:RGD.
DR GO; GO:0005829; C:cytosol; IDA:RGD.
DR GO; GO:0030425; C:dendrite; IDA:RGD.
DR GO; GO:0043197; C:dendritic spine; IDA:RGD.
DR GO; GO:0016021; C:integral component of membrane; IEA:UniProtKB-KW.
DR GO; GO:0016020; C:membrane; IDA:RGD.
DR GO; GO:0045211; C:postsynaptic membrane; IDA: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: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; ISS:UniProtKB.
DR GO; GO:0016036; P:cellular response to phosphate starvation; ISO:RGD.
DR GO; GO:0032502; P:developmental process; IEP:RGD.
DR GO; GO:0042420; P:dopamine catabolic process; ISO:RGD.
DR GO; GO:0042417; P:dopamine metabolic process; ISO:RGD.
DR GO; GO:0008210; P:estrogen metabolic process; IMP:RGD.
DR GO; GO:0007565; P:female pregnancy; IMP:RGD.
DR GO; GO:0007612; P:learning; IMP:RGD.
DR GO; GO:0032259; P:methylation; ISS:UniProtKB.
DR GO; GO:0048609; P:multicellular organismal reproductive process; IMP:RGD.
DR GO; GO:0045963; P:negative regulation of dopamine metabolic process; IMP:RGD.
DR GO; GO:0035814; P:negative regulation of renal sodium excretion; IMP:RGD.
DR GO; GO:0048662; P:negative regulation of smooth muscle cell proliferation; IMP:RGD.
DR GO; GO:0042135; P:neurotransmitter catabolic process; IEA:UniProtKB-KW.
DR GO; GO:0050668; P:positive regulation of homocysteine metabolic process; IMP:RGD.
DR GO; GO:0051930; P:regulation of sensory perception of pain; IMP:RGD.
DR GO; GO:0043627; P:response to estrogen; IEP: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:0048265; P:response to pain; IMP: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 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; 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
