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Literature summary extracted from

  • Satta, R.; Maloku, E.; Zhubi, A.; Pibiri, F.; Hajos, M.; Costa, E.; Guidotti, A.
    Nicotine decreases DNA methyltransferase 1 expression and glutamic acid decarboxylase 67 promoter methylation in GABAergic interneurons (2008), Proc. Natl. Acad. Sci. USA, 105, 16356-16361.
    View publication on PubMedView publication on EuropePMC

Activating Compound

EC Number Activating Compound Comment Organism Structure
4.1.1.15 additional information nicotine decreases inhibitory DNA-methyltransferase 1 mRNA and protein and increases GAD67 expression in the mouse frontal cortex, it diminishes the level of cytosine-5-methylation in the GAD67 promoter and prevents the methionine-induced hypermethylation of the same promoter. Nicotine effects are prevented by pretreatment with mecamylamine, overview Mus musculus

Application

EC Number Application Comment Organism
4.1.1.15 diagnostics the enzyme is a potential important marker for the prediction and diagnosis of type 1 diabetes Homo sapiens
4.1.1.15 pharmacology the enzyme is a potential important marker for the prediction and diagnosis of type 1 diabetes, and for the development of antigen-specific therapies for the treatment of type 1 diabetes Homo sapiens

Cloned(Commentary)

EC Number Cloned (Comment) Organism
4.1.1.15 gene GAD65, recombinant expression of full-length human GAD65 in Chlamydomonas reinhardtii strain 137c chloroplast genome under the control of the Chlamydomonas reinhardtii chloroplast rbcL promoter and 5'- and 3'-UTRs by particle bombardment Homo sapiens
4.1.1.15 gene GAD67, expression analysis Mus musculus

Protein Variants

EC Number Protein Variants Comment Organism
4.1.1.15 additional information construction of transgenic Chlamydomonas reinhardtii expressing the human enzyme in chloroplasts, expression analysis and immunohistochemic protein detection, overview Homo sapiens

Inhibitors

EC Number Inhibitors Comment Organism Structure
2.1.1.37 Nicotine decreases glutamic acid decarboxylase 67 promoter methylation by DMT1 in GABAergic interneurons Mus musculus
4.1.1.15 additional information downregulation of reelin and GAD67 expression by the increase of DNA-methyltransferase 1-mediated hypermethylation of promoters in GABAergic interneurons of the telencephalon Mus musculus

Localization

EC Number Localization Comment Organism GeneOntology No. Textmining
2.1.1.37 nucleus
-
 Mus musculus 5634
-

Natural Substrates/ Products (Substrates)

EC Number Natural Substrates Organism Comment (Nat. Sub.) Natural Products Comment (Nat. Pro.) Rev. Reac.
4.1.1.15 L-glutamate Homo sapiens human glutamic acid decarboxylase 65 is a key autoantigen in type 1 diabetes 4-aminobutanoate + CO2
-
 ?
4.1.1.15 L-glutamate Mus musculus nicotine, by activating nAChRs located on cortical or hippocampal GABAergic interneurons, can up-regulate GAD67 expression via an epigenetic mechanism 4-aminobutanoate + CO2
-
 ?

Organism

EC Number Organism UniProt Comment Textmining
2.1.1.37 Mus musculus
-
 Swiss albino male mice
-
4.1.1.15 Homo sapiens
-
 gene GAD65
-
4.1.1.15 Mus musculus
-
-
-

Source Tissue

EC Number Source Tissue Comment Organism Textmining
2.1.1.37 brain
-
 Mus musculus
-
2.1.1.37 central nervous system
-
 Mus musculus
-
2.1.1.37 liver
-
 Mus musculus
-
2.1.1.37 neuron cortical, hippocampal, and striatal GABAergic neurons Mus musculus
-
4.1.1.15 brain
-
 Mus musculus
-
4.1.1.15 frontal lobe
-
 Mus musculus
-
4.1.1.15 hippocampus
-
 Mus musculus
-
4.1.1.15 neuron GABAergic interneuron Mus musculus
-

Substrates and Products (Substrate)

EC Number Substrates Comment Substrates Organism Products Comment (Products) Rev. Reac.
4.1.1.15 L-glutamate
-
 Mus musculus 4-aminobutanoate + CO2
-
 ?
4.1.1.15 L-glutamate
-
 Homo sapiens 4-aminobutanoate + CO2
-
 ?
4.1.1.15 L-glutamate human glutamic acid decarboxylase 65 is a key autoantigen in type 1 diabetes Homo sapiens 4-aminobutanoate + CO2
-
 ?
4.1.1.15 L-glutamate nicotine, by activating nAChRs located on cortical or hippocampal GABAergic interneurons, can up-regulate GAD67 expression via an epigenetic mechanism Mus musculus 4-aminobutanoate + CO2
-
 ?

Synonyms

EC Number Synonyms Comment Organism
2.1.1.37 DMT1
-
 Mus musculus
2.1.1.37 DNA methyltransferase 1
-
 Mus musculus
4.1.1.15 GAD65
-
 Homo sapiens
4.1.1.15 GAD67
-
 Mus musculus
4.1.1.15 glutamic acid decarboxylase 67
-
 Mus musculus
4.1.1.15 glutamic acid decarboxylase-65
-
 Homo sapiens

Expression

EC Number Organism Comment Expression
2.1.1.37 Mus musculus nicotine decreases DNA methyltransferase 1 expression in in cortical and hippocampal but not in striatal GABAergic interneurons, while DNMT1 mRNA content in the liver fails to change after nicotine treatment, overview. Mecamylamine but not hexamethonium blocks nicotine-induced downregulation of DNMT1 expression. The downregulation proceeds via selective stimulation of nicotinic acetylcholine receptor, nAChR, overview down