COMT_HORSE
ID COMT_HORSE Reviewed; 269 AA.
AC Q5H879; Q5H878;
DT 05-FEB-2008, integrated into UniProtKB/Swiss-Prot.
DT 01-MAR-2005, sequence version 1.
DT 03-AUG-2022, entry version 103.
DE RecName: Full=Catechol O-methyltransferase {ECO:0000305};
DE EC=2.1.1.6 {ECO:0000250|UniProtKB:P21964};
GN Name=COMT;
OS Equus caballus (Horse).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Laurasiatheria; Perissodactyla; Equidae; Equus.
OX NCBI_TaxID=9796;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA], VARIANT THR-120, AND ALTERNATIVE INITIATION.
RX PubMed=15771748; DOI=10.1111/j.1365-2052.2005.01265.x;
RA Momozawa Y., Takeuchi Y., Tozaki T., Kikusui T., Hasegawa T., Raudsepp T.,
RA Chowdhary B.P., Kusunose R., Mori Y.;
RT "Sequence, detection of polymorphisms and radiation hybrid mapping of the
RT equine catechol-O-methyltransferase gene.";
RL Anim. Genet. 36:190-190(2005).
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: [Isoform Soluble]: Cytoplasm
CC {ECO:0000250|UniProtKB:P22734}.
CC -!- SUBCELLULAR LOCATION: [Isoform Membrane-bound]: Cell membrane
CC {ECO:0000250|UniProtKB:P22734}; Single-pass type II membrane protein
CC {ECO:0000255}; Extracellular side {ECO:0000250|UniProtKB:P22734}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative initiation; Named isoforms=2;
CC Name=Membrane-bound; Synonyms=MB-COMT;
CC IsoId=Q5H879-1; Sequence=Displayed;
CC Name=Soluble; Synonyms=S-COMT;
CC IsoId=Q5H879-2; Sequence=VSP_031176;
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 EMBL; AB178284; BAD89294.1; -; mRNA.
DR EMBL; AB178284; BAD89295.1; -; mRNA.
DR RefSeq; NP_001075303.1; NM_001081834.1. [Q5H879-1]
DR RefSeq; NP_001108007.1; NM_001114535.1. [Q5H879-2]
DR AlphaFoldDB; Q5H879; -.
DR SMR; Q5H879; -.
DR STRING; 9796.ENSECAP00000047104; -.
DR PaxDb; Q5H879; -.
DR PeptideAtlas; Q5H879; -.
DR PRIDE; Q5H879; -.
DR GeneID; 100146509; -.
DR KEGG; ecb:100146509; -.
DR CTD; 1312; -.
DR InParanoid; Q5H879; -.
DR OrthoDB; 1274244at2759; -.
DR Proteomes; UP000002281; 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:0016021; C:integral component of membrane; IEA:UniProtKB-KW.
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 2: Evidence at transcript level;
KW Alternative initiation; Catecholamine metabolism; Cell membrane; Cytoplasm;
KW Lipid metabolism; Magnesium; Membrane; Metal-binding; Methyltransferase;
KW Neurotransmitter degradation; Phosphoprotein; Reference proteome;
KW S-adenosyl-L-methionine; Signal-anchor; Transferase; Transmembrane;
KW Transmembrane helix.
FT CHAIN 1..269
FT /note="Catechol O-methyltransferase"
FT /id="PRO_0000318147"
FT TOPO_DOM 1..4
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 5..25
FT /note="Helical; Signal-anchor for type II membrane protein"
FT /evidence="ECO:0000255"
FT TOPO_DOM 26..269
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT BINDING 89
FT /ligand="S-adenosyl-L-methionine"
FT /ligand_id="ChEBI:CHEBI:59789"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01019"
FT BINDING 111
FT /ligand="S-adenosyl-L-methionine"
FT /ligand_id="ChEBI:CHEBI:59789"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01019"
FT BINDING 119
FT /ligand="S-adenosyl-L-methionine"
FT /ligand_id="ChEBI:CHEBI:59789"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01019"
FT BINDING 137
FT /ligand="S-adenosyl-L-methionine"
FT /ligand_id="ChEBI:CHEBI:59789"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01019"
FT BINDING 138
FT /ligand="S-adenosyl-L-methionine"
FT /ligand_id="ChEBI:CHEBI:59789"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01019"
FT BINDING 164..167
FT /ligand="S-adenosyl-L-methionine"
FT /ligand_id="ChEBI:CHEBI:59789"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01019"
FT BINDING 166
FT /ligand="S-adenosyl-L-methionine"
FT /ligand_id="ChEBI:CHEBI:59789"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01019"
FT BINDING 188
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /evidence="ECO:0000250"
FT BINDING 188
FT /ligand="S-adenosyl-L-methionine"
FT /ligand_id="ChEBI:CHEBI:59789"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01019"
FT BINDING 191
FT /ligand="substrate"
FT /evidence="ECO:0000250"
FT BINDING 216
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /evidence="ECO:0000250"
FT BINDING 217
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /evidence="ECO:0000250"
FT BINDING 217
FT /ligand="substrate"
FT /evidence="ECO:0000250"
FT BINDING 246
FT /ligand="substrate"
FT /evidence="ECO:0000250"
FT MOD_RES 265
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P22734"
FT VAR_SEQ 1..47
FT /note="Missing (in isoform Soluble)"
FT /evidence="ECO:0000305"
FT /id="VSP_031176"
FT VARIANT 120
FT /note="A -> T"
FT /evidence="ECO:0000269|PubMed:15771748"
SQ SEQUENCE 269 AA; 30028 MW; 73A24585C6768C44 CRC64;
MLEPTPMLLA AFSLGLALLP LLFFLRRWGW LLIGWNECIL QPIHNLLMGD SKEQRILRHV
LQHAVAGDPQ SVLETIDAYC SQKEWAMNVG DKKGQFLDAV VQEQQPSVLL ELGAYCGYSA
VRMARLLPPG ARLLTIEINP DYAAITQRML DFAGLQDRVT VVLGASQDII PQLKKKYDVD
TLDVVFLDHW KDRYLPDTLL LEECGLLRKG TVLLADNVIV PGAPDFLAHV RGSGRFECTH
FSSYLEYSLW VVDGVEKAVY LGPGSPAQP
