COMT_PIG
ID COMT_PIG Reviewed; 186 AA.
AC Q99028;
DT 01-JUN-1994, integrated into UniProtKB/Swiss-Prot.
DT 01-JUN-1994, sequence version 1.
DT 03-AUG-2022, entry version 117.
DE RecName: Full=Catechol O-methyltransferase {ECO:0000305};
DE EC=2.1.1.6 {ECO:0000250|UniProtKB:P21964};
DE Flags: Fragment;
GN Name=COMT;
OS Sus scrofa (Pig).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Laurasiatheria; Artiodactyla; Suina; Suidae; Sus.
OX NCBI_TaxID=9823;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
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 [2]
RP PARTIAL PROTEIN SEQUENCE.
RC TISSUE=Liver;
RX PubMed=1932084; DOI=10.1016/0167-4838(91)90135-m;
RA Bertocci B., Garotta G., da Prada M., Lahm H.-W., Zurcher G.,
RA Virgallita G., Miggiano V.;
RT "Immunoaffinity purification and partial amino acid sequence analysis of
RT catechol-O-methyltransferase from pig liver.";
RL Biochim. Biophys. Acta 1080:103-109(1991).
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:0000250|UniProtKB:P21964}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=a catechol + S-adenosyl-L-methionine = a guaiacol + H(+) + S-
CC adenosyl-L-homocysteine; Xref=Rhea:RHEA:17877, ChEBI:CHEBI:15378,
CC ChEBI:CHEBI:33566, ChEBI:CHEBI:57856, ChEBI:CHEBI:59789,
CC ChEBI:CHEBI:134251; EC=2.1.1.6;
CC Evidence={ECO:0000250|UniProtKB:P21964};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:17878;
CC Evidence={ECO:0000250|UniProtKB:P21964};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=2-hydroxyestrone + S-adenosyl-L-methionine = 2-hydroxy-3-
CC methoxy-estrone + H(+) + S-adenosyl-L-homocysteine;
CC Xref=Rhea:RHEA:53108, ChEBI:CHEBI:1156, ChEBI:CHEBI:15378,
CC ChEBI:CHEBI:57856, ChEBI:CHEBI:59789, ChEBI:CHEBI:136980;
CC Evidence={ECO:0000250|UniProtKB:P21964};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:53109;
CC Evidence={ECO:0000250|UniProtKB:P21964};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=4-hydroxyestrone + S-adenosyl-L-methionine = 4-methoxyestrone
CC + H(+) + S-adenosyl-L-homocysteine; Xref=Rhea:RHEA:53104,
CC ChEBI:CHEBI:15378, ChEBI:CHEBI:57856, ChEBI:CHEBI:59789,
CC ChEBI:CHEBI:87602, ChEBI:CHEBI:136972;
CC Evidence={ECO:0000250|UniProtKB:P21964};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:53105;
CC Evidence={ECO:0000250|UniProtKB:P21964};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=2-hydroxyestrone + S-adenosyl-L-methionine = 2-methoxyestrone
CC + H(+) + S-adenosyl-L-homocysteine; Xref=Rhea:RHEA:53100,
CC ChEBI:CHEBI:1156, ChEBI:CHEBI:1189, ChEBI:CHEBI:15378,
CC ChEBI:CHEBI:57856, ChEBI:CHEBI:59789;
CC Evidence={ECO:0000250|UniProtKB:P21964};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:53101;
CC Evidence={ECO:0000250|UniProtKB:P21964};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=4-hydroxy-17beta-estradiol + S-adenosyl-L-methionine = 4-
CC methoxy-17beta-estradiol + H(+) + S-adenosyl-L-homocysteine;
CC Xref=Rhea:RHEA:53096, ChEBI:CHEBI:15378, ChEBI:CHEBI:57856,
CC ChEBI:CHEBI:59789, ChEBI:CHEBI:62845, ChEBI:CHEBI:136975;
CC Evidence={ECO:0000250|UniProtKB:P21964};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:53097;
CC Evidence={ECO:0000250|UniProtKB:P21964};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=2-hydroxy-17beta-estradiol + S-adenosyl-L-methionine = 2-
CC hydroxy-3-methoxy-17beta-estradiol + H(+) + S-adenosyl-L-
CC homocysteine; Xref=Rhea:RHEA:53092, ChEBI:CHEBI:15378,
CC ChEBI:CHEBI:28744, ChEBI:CHEBI:57856, ChEBI:CHEBI:59789,
CC ChEBI:CHEBI:89268; Evidence={ECO:0000250|UniProtKB:P21964};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:53093;
CC Evidence={ECO:0000250|UniProtKB:P21964};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=2-hydroxy-17beta-estradiol + S-adenosyl-L-methionine = 2-
CC methoxy-17beta-estradiol + H(+) + S-adenosyl-L-homocysteine;
CC Xref=Rhea:RHEA:53088, ChEBI:CHEBI:15378, ChEBI:CHEBI:28744,
CC ChEBI:CHEBI:28955, ChEBI:CHEBI:57856, ChEBI:CHEBI:59789;
CC Evidence={ECO:0000250|UniProtKB:P21964};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:53089;
CC Evidence={ECO:0000250|UniProtKB:P21964};
CC -!- COFACTOR:
CC Name=Mg(2+); Xref=ChEBI:CHEBI:18420;
CC Evidence={ECO:0000250|UniProtKB:P22734};
CC Note=Binds 1 Mg(2+) ion per subunit. {ECO:0000250|UniProtKB:P22734};
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000250|UniProtKB:P22734}. Cell
CC membrane {ECO:0000250|UniProtKB:P22734}; Single-pass type II membrane
CC protein {ECO:0000250|UniProtKB:P22734}; Extracellular side
CC {ECO:0000250|UniProtKB:P22734}.
CC -!- SIMILARITY: Belongs to the class I-like SAM-binding methyltransferase
CC superfamily. Cation-dependent O-methyltransferase family.
CC {ECO:0000255|PROSITE-ProRule:PRU01019}.
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DR AlphaFoldDB; Q99028; -.
DR SMR; Q99028; -.
DR STRING; 9823.ENSSSCP00000010805; -.
DR BindingDB; Q99028; -.
DR ChEMBL; CHEMBL2176837; -.
DR PaxDb; Q99028; -.
DR PeptideAtlas; Q99028; -.
DR PRIDE; Q99028; -.
DR eggNOG; KOG1663; Eukaryota.
DR InParanoid; Q99028; -.
DR ChiTaRS; COMT; pig.
DR Proteomes; UP000008227; Unplaced.
DR Proteomes; UP000314985; Unplaced.
DR GO; GO:0030424; C:axon; IBA:GO_Central.
DR GO; GO:0005829; C:cytosol; ISS:UniProtKB.
DR GO; GO:0030425; C:dendrite; IBA:GO_Central.
DR GO; GO:0016020; C:membrane; IBA:GO_Central.
DR GO; GO:0005886; C:plasma membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0016206; F:catechol O-methyltransferase activity; ISS: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: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:0032502; P:developmental process; IBA:GO_Central.
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; ISS: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 Catecholamine metabolism; Cell membrane; Cytoplasm;
KW Direct protein sequencing; Lipid metabolism; Magnesium; Membrane;
KW Metal-binding; Methyltransferase; Neurotransmitter degradation;
KW Phosphoprotein; Reference proteome; S-adenosyl-L-methionine; Transferase.
FT CHAIN <1..186
FT /note="Catechol O-methyltransferase"
FT /id="PRO_0000090016"
FT BINDING 7
FT /ligand="S-adenosyl-L-methionine"
FT /ligand_id="ChEBI:CHEBI:59789"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01019"
FT BINDING 29
FT /ligand="S-adenosyl-L-methionine"
FT /ligand_id="ChEBI:CHEBI:59789"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01019"
FT BINDING 37
FT /ligand="S-adenosyl-L-methionine"
FT /ligand_id="ChEBI:CHEBI:59789"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01019"
FT BINDING 55
FT /ligand="S-adenosyl-L-methionine"
FT /ligand_id="ChEBI:CHEBI:59789"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01019"
FT BINDING 56
FT /ligand="S-adenosyl-L-methionine"
FT /ligand_id="ChEBI:CHEBI:59789"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01019"
FT BINDING 82..85
FT /ligand="S-adenosyl-L-methionine"
FT /ligand_id="ChEBI:CHEBI:59789"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01019"
FT BINDING 84
FT /ligand="S-adenosyl-L-methionine"
FT /ligand_id="ChEBI:CHEBI:59789"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01019"
FT BINDING 106
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /evidence="ECO:0000250"
FT BINDING 106
FT /ligand="S-adenosyl-L-methionine"
FT /ligand_id="ChEBI:CHEBI:59789"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01019"
FT BINDING 109
FT /ligand="substrate"
FT /evidence="ECO:0000250"
FT BINDING 134
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /evidence="ECO:0000250"
FT BINDING 135
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /evidence="ECO:0000250"
FT BINDING 135
FT /ligand="substrate"
FT /evidence="ECO:0000250"
FT BINDING 164
FT /ligand="substrate"
FT /evidence="ECO:0000250"
FT MOD_RES 182
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P22734"
FT NON_TER 1
SQ SEQUENCE 186 AA; 20587 MW; 493B8801F06C6262 CRC64;
KERAMHVGRK KGQIVDTVVQ EQRPSVLLEL GAYCGYSAVR MARLLLPSAR LLTIELNPDN
AAIAQQVVDF AGLQDRVTVV VGASQDIIPQ LKKKYDVDTL DMVFLDHWKD RYLPDTLLLE
ECGLLRKGTV LLADNVICPG APDFLAHVRG CGRFECTHFS SYLEYSQMVD GLEKAVYKGP
GSPAQP
