Catechol O-methyltransferase

Function

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.

Classification

Family (Pfam)

PF01596 Methyltransf_3

InterPro

Catechol_O-MeTrfase_euk, SAM-dependent_MTases_sf, SAM_O-MeTrfase

Functional cluster

Membrane Channels & Lipid-Anchored Proteins

Experimental structures · PDB · 12

• 3A7E X-ray 2.80A
• 3BWM X-ray 1.98A
• 3BWY X-ray 1.30A
• 4PYI X-ray 1.35A
• 4PYJ X-ray 1.90A
• 4PYK X-ray 2.22A
• 4XUC X-ray 1.80A
• 4XUD X-ray 2.40A
• 4XUE X-ray 2.30A
• 5LSA X-ray 1.50A
• 6I3C X-ray 1.34A
• 6I3D X-ray 1.45A

A predicted model is available from AlphaFold.

Gene Ontology · 17

• GO:0030424 axon
• GO:0005829 cytosol
• GO:0030425 dendrite
• GO:0005783 endoplasmic reticulum
• GO:0070062 extracellular exosome
• GO:0016020 membrane
• GO:0005886 plasma membrane
• GO:0016206 catechol O-methyltransferase activity
• GO:0000287 magnesium ion binding
• GO:0008168 methyltransferase activity
• GO:0008171 O-methyltransferase activity
• GO:0042424 catecholamine catabolic process
• GO:0032502 developmental process
• GO:0042420 dopamine catabolic process
• GO:0042417 dopamine metabolic process
• GO:0006629 lipid metabolic process
• GO:0032259 methylation

Disease associations

• alcohol dependence MONDO:0007079
• schizophrenia MONDO:0005090
• OMIM:621296 RAW:OMIM_621296

Drugs targeting this protein · 4

• OPICAPONE inhibitor
• TOLCAPONE inhibitor
• NEBICAPONE inhibitor
• ENTACAPONE inhibitor

Related proteins · sequence + function similarity

• Catechol O-methyltransferase 0.97
• Catechol O-methyltransferase 0.97
• Catechol O-methyltransferase 0.96
• Catechol O-methyltransferase 0.95
• Catechol O-methyltransferase B 0.83
• Catechol O-methyltransferase 0.83
• Catechol O-methyltransferase A 0.77
• Transmembrane O-methyltransferase 0.76
• Transmembrane O-methyltransferase 0.76
• Transmembrane O-methyltransferase 0.75
• Transmembrane O-methyltransferase 0.74
• Transmembrane O-methyltransferase homolog 0.73

Co-cited proteins · studied together in the literature

• Catechol O-methyltransferase 1 shared papers
• Catechol O-methyltransferase 1 shared papers

Literature · 22 cited papers

• N-terminome analysis of the human mitochondrial proteome. Proteomics · 2015
• An enzyme assisted RP-RPLC approach for in-depth analysis of human liver phosphoproteome. J. Proteomics · 2014
• Orientation and cellular distribution of membrane-bound catechol-O-methyltransferase in cortical neurons: implications for drug development. J. Biol. Chem. · 2011
• Initial characterization of the human central proteome. BMC Syst. Biol. · 2011
• Crystal structures of human 108V and 108M catechol O-methyltransferase. J. Mol. Biol. · 2008
• The V108M mutation decreases the structural stability of catechol O-methyltransferase. Biochim. Biophys. Acta · 2008
• Catechol O-methyltransferase val158-met polymorphism is associated with abdominal obesity and blood pressure in men. Metabolism · 2008
• Association of Ala72Ser polymorphism with COMT enzyme activity and the risk of schizophrenia in Koreans. Hum. Genet. · 2005
• The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC). Genome Res. · 2004
• A genome annotation-driven approach to cloning the human ORFeome. Genome Biol. · 2004
• Complete sequencing and characterization of 21,243 full-length human cDNAs. Nat. Genet. · 2004
• Catechol-O-methyltransferase (COMT)-mediated metabolism of catechol estrogens: comparison of wild-type and variant COMT isoforms. Cancer Res. · 2001
• … and 10 more in the literature graph