Search
catechol O-methyltransferase (COMT)
Function:
- catalyzes the O-methylation, & thus inactivation, of catecholamine neurotransmitters & catechol hormones
- transfers methyl group from SAM to catecholamines
- both a soluble & membrane-bound form from same precursor
- shortens the biological half-lives of certain neuroactive drugs, including L-DOPA, alpha-methyl DOPA & isoproterenol
S-adenosyl-L-methionine + a catechol
S-adenosyl-L-homocysteine + a guaiacol
Cofactor: binds 1 Mg+2 per subunit (putative)
Structure:
- N-terminus is blocked
- belongs to the mammalian catechol-O-methyltransferase family
Compartment:
- isoform soluble: cytoplasm
- isoform membrane-bound: cell membrane, extracellular side
Alternative initiation:
- named isoforms=2
Expression:
- brain, liver, placenta, lymphocytes & erythrocytes
Polymorphism:
- low enzyme activity alleles are associated with genetic susceptibility to alcoholism [4]
- val158met polymorphism predicts placebo effect in irritable bowel syndrome [5]
Laboratory:
- COMT gene mutation
Interactions
molecular events
Related
catechol O-methyltransferase 2 (COMT2)
catecholamine metabolism
General
O-methyl transferase
Properties
SIZE: entity length = 271 aa
MW = 30 kD
COMPARTMENT: cytoplasm
cellular membrane
MOTIF: transmembrane domain {7-26}
binding site
SITE: 92-92
FOR-BINDING-OF: S-adenosylmethionine
binding site
SITE: 122-122
FOR-BINDING-OF: S-adenosylmethionine
binding site
SITE: 140-140
FOR-BINDING-OF: S-adenosylmethionine
Mg+2-binding site
SITE: 191-191
MOTIF: binding site
SITE: 191-191
FOR-BINDING-OF: S-adenosylmethionine
binding site
SITE: 194-194
FOR-BINDING-OF: Substrate
Mg+2-binding site
SITE: 219-219
Mg+2-binding site
SITE: 220-220
MOTIF: binding site
SITE: 220-220
FOR-BINDING-OF: Substrate
binding site
SITE: 249-249
FOR-BINDING-OF: Substrate
Ser phosphorylation site {S267}
Database Correlations
OMIM correlations
MORBIDMAP 116790
UniProt P21964
Pfam PF01596
KEGG correlations
ENZYME 2.1.1.6
References
- OMIM :accession 116790
- UniProt :accession P21964
- Wikipedia: catechol-O-methyl transferase entry
http://en.wikipedia.org/wiki/catechol-O-methyl_transferase
- OMIM :accession 103780
- Hall KT et al.
Catechol-O-methyltransferase val158met polymorphism predicts
placebo effect in irritable bowel syndrome.
PLoS ONE 2012 Oct 23; 7:e48135.
PMID: 23110189