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   12-AUG-2020, entry version 112.
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   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   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:0032259; P:methylation; ISS:UniProtKB.
DR   GO; GO:0042135; P:neurotransmitter catabolic process; IEA:UniProtKB-KW.
DR   InterPro; IPR017128; Catechol_O-MeTrfase_euk.
DR   InterPro; IPR029063; SAM-dependent_MTases.
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; Magnesium; Membrane; Metal-binding;
KW   Methyltransferase; Neurotransmitter degradation; Phosphoprotein;
KW   Reference proteome; S-adenosyl-L-methionine; Transferase.
FT   CHAIN           <1..186
FT                   /note="Catechol O-methyltransferase"
FT                   /id="PRO_0000090016"
FT   REGION          82..85
FT                   /note="S-adenosyl-L-methionine binding"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU01019"
FT   METAL           106
FT                   /note="Magnesium"
FT                   /evidence="ECO:0000250"
FT   METAL           134
FT                   /note="Magnesium"
FT                   /evidence="ECO:0000250"
FT   METAL           135
FT                   /note="Magnesium"
FT                   /evidence="ECO:0000250"
FT   BINDING         7
FT                   /note="S-adenosyl-L-methionine; via amide nitrogen"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU01019"
FT   BINDING         29
FT                   /note="S-adenosyl-L-methionine"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU01019"
FT   BINDING         37
FT                   /note="S-adenosyl-L-methionine"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU01019"
FT   BINDING         55
FT                   /note="S-adenosyl-L-methionine"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU01019"
FT   BINDING         56
FT                   /note="S-adenosyl-L-methionine; via amide nitrogen"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU01019"
FT   BINDING         84
FT                   /note="S-adenosyl-L-methionine; via amide nitrogen"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU01019"
FT   BINDING         106
FT                   /note="S-adenosyl-L-methionine"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU01019"
FT   BINDING         109
FT                   /note="Substrate"
FT                   /evidence="ECO:0000250"
FT   BINDING         135
FT                   /note="Substrate"
FT                   /evidence="ECO:0000250"
FT   BINDING         164
FT                   /note="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
//