Catechol O-methyltransferase (COMT)

The protein contains 271 amino acids for an estimated molecular weight of 30037 Da.

 

Catalyzes the O-methylation, and thereby the inactivation, of catecholamine neurotransmitters and catechol hormones. Also shortens the biological half-lives of certain neuroactive drugs, like L-DOPA, alpha-methyl DOPA and isoproterenol. (updated: March 4, 2015)

Protein identification was indicated in the following studies:

  1. Goodman and co-workers. (2013) The proteomics and interactomics of human erythrocytes. Exp Biol Med (Maywood) 238(5), 509-518.
  2. Hegedűs and co-workers. (2015) Inconsistencies in the red blood cell membrane proteome analysis: generation of a database for research and diagnostic applications. Database (Oxford) 1-8.
  3. Wilson and co-workers. (2016) Comparison of the Proteome of Adult and Cord Erythroid Cells, and Changes in the Proteome Following Reticulocyte Maturation. Mol Cell Proteomics. 15(6), 1938-1946.
  4. Bryk and co-workers. (2017) Quantitative Analysis of Human Red Blood Cell Proteome. J Proteome Res. 16(8), 2752-2761.
  5. D'Alessandro and co-workers. (2017) Red blood cell proteomics update: is there more to discover? Blood Transfus. 15(2), 182-187.
  6. Chu and co-workers. (2018) Quantitative mass spectrometry of human reticulocytes reveal proteome-wide modifications during maturation. Br J Haematol. 180(1), 118-133.

Methods

The following articles were analysed to gather the proteome content of erythrocytes.

The gene or protein list provided in the studies were processed using the ID mapping API of Uniprot in September 2018. The number of proteins identified and mapped without ambiguity in these studies is indicated below.
Only Swiss-Prot entries (reviewed) were considered for protein evidence assignation.

PublicationIdentification 1Uniprot mapping 2Not mapped /
Obsolete
TrEMBLSwiss-Prot
Goodman (2013)2289 (gene list)227853205992269
Lange (2014)123412347281224
Hegedus (2015)2638262202352387
Wilson (2016)165815281702911068
d'Alessandro (2017)18261817201815
Bryk (2017)20902060101081942
Chu (2018)18531804553621387

1 as available in the article and/or in supplementary material
2 uniprot mapping returns all protein isoforms as one entry

The compilation of older studies can be retrieved from the Red Blood Cell Collection database.

The data and differentiation stages presented below come from the proteomic study and analysis performed by our partners of the GReX consortium, more details are available in their published work.

No sequence conservation computed yet.

This protein is annotated as membranous in Gene Ontology, is annotated as membranous in UniProt, is predicted to be membranous by TOPCONS.


Interpro domains
Total structural coverage: 82%
Model score: 0
No model available.

(right-click above to access to more options from the contextual menu)

VariantDescription
dbSNP:rs6270
Correlated with reduced enzyme activity
dbSNP:rs5031015
dbSNP:rs4986871
allele COMT*2

The reference OMIM entry for this protein is 103780

Alcohol dependence
Alcoholism

A number sign (#) is used with this entry because of the demonstrated role of multiple genes in determining the genetic susceptibility for alcoholism that is supported by family, twin, and other studies. See

MOLECULAR GENETICS

below.

INHERITANCE

The tendency for drinking patterns of children to resemble those of their parents has been recognized since antiquity, e.g., in the observations of Plato and Aristotle (Warner and Rosett, 1975). Alcoholism is probably a multifactorial, genetically influenced disorder (Goodwin, 1976). The genetic influence is indicated by studies showing that (1) there is a 25 to 50% lifetime risk for alcoholism in sons and brothers of severely alcoholic men; (2) alcohol preference can be selectively bred for in experimental animals; (3) there is a 55% or higher concordance rate in monozygotic twins with only a 28% rate for like-sex dizygotic twins; and (4) half brothers with different fathers and adopted sons of alcoholic men show a rate of alcoholism more like that of the biologic father than that of the foster father. A possible biochemical basis is a metabolic difference such that those prone to alcoholism have higher levels of a metabolite giving pleasurable effects or those not prone to alcoholism have higher levels of a metabolite giving unpleasant effects. Schuckit and Rayses (1979) found that, after a moderate dose of alcohol, blood acetaldehyde levels were elevated more in young men with alcoholic parents or sibs than in controls. A certain degree of organ specificity in the pathologic effects of alcohol is observed. For example, patients have cardiomyopathy, cirrhosis, or pancreatitis but rarely more than one of these. A genetic basis of organ specificity is evident in Wernicke-Korsakoff syndrome (277730) and pancreatitis from type V hyperlipidemia (144650). Cloninger (1987) identified 2 separate heritable types of alcoholism. Type 1 alcohol abuse had its usual onset after the age of 25 years and was characterized by severe psychological dependence and guilt. It occurred in both men and women and required both genetic and environmental factors to become manifest. By contrast, type 2 alcohol abuse had its onset before the age of 25; persons with this type of alcoholism were characterized by their inability to abstain from alcohol and by frequent aggressive and antisocial behavior. Type 2 alcoholism was rarely found in women and was much more heritable. Abnormalities in platelet monoamine oxidase activity were found only in type 2 alcoholics (Von Knorring et al., 1985). See comments by Omenn (1988). Crabb (1990) reviewed biologic markers for increased risk of alcoholism. Aston and Hill (1990) performed complex segregation analysis of 35 multigenerational families ascertained through a pair of male alcoholics. They concluded that liability to alcoholism is, in part, controlled by a major effect with or without additional multifactorial effects. However, mendelian transmission of this major effect was rejected, as was the hypothesis that the major effect is due to a single major locus. In connection with a collection of 11 research reports on the genetics of alcohol-related traits, Buck (1998) gave a brief review on recent progress toward the identification of genes related to risk for alcoholism.

MAPPING

Nurnberger et al. (2001) reported linkage data indicating that a susceptibility locus for alcoholism and/or depression phenotypes resides on chromosome 1p. Using short tan ... More on the omim web site

Subscribe to this protein entry history

Feb. 2, 2018: Protein entry updated
Automatic update: Uniprot description updated

Dec. 19, 2017: Protein entry updated
Automatic update: Uniprot description updated

Nov. 23, 2017: Protein entry updated
Automatic update: Uniprot description updated

March 16, 2016: Protein entry updated
Automatic update: OMIM entry 103780 was added.

Jan. 27, 2016: Protein entry updated
Automatic update: model status changed

Jan. 24, 2016: Protein entry updated
Automatic update: model status changed