Target type: molecularfunction
Catalysis of the reaction: 5-methylcytosine (5mC) in DNA + 2-oxoglutarate + O2 = 5-hydroxymethylcytosine (5hmC) in DNA + succinate + CO2. This reaction is the first step in the removal of cytosine methylated on position 5 in double-stranded DNA. This activity can iteratively oxidize 5hmC to 5-formylcytosine (5fC) and to 5-carboxylcytosine (5caC). [PMID:19372391, PMID:21496894, PMID:21778364]
5-Methylcytosine dioxygenase activity is a critical molecular function in DNA methylation, a fundamental epigenetic modification involved in regulating gene expression and various cellular processes. 5-Methylcytosine (5mC) is a modified base in DNA, and its presence can affect the accessibility of DNA to transcription factors, ultimately impacting gene expression. 5-Methylcytosine dioxygenases, also known as ten-eleven translocation (TET) enzymes, catalyze the oxidation of 5mC to 5-hydroxymethylcytosine (5hmC) and further to 5-formylcytosine (5fC) and 5-carboxylcytosine (5caC). This enzymatic activity plays a crucial role in DNA demethylation pathways, where 5mC is progressively oxidized to eventually be replaced with unmodified cytosine. The oxidation of 5mC by TET enzymes is a complex process that involves the incorporation of molecular oxygen, with the assistance of cofactors like α-ketoglutarate and iron. This oxidation reaction requires the TET enzymes to bind specifically to 5mC within the DNA molecule. The TET family of enzymes consists of three members: TET1, TET2, and TET3, each with distinct expression patterns and roles in development and disease. The activity of TET enzymes is tightly regulated by various factors, including cellular signaling pathways, cellular context, and interactions with other proteins. Dysregulation of 5-methylcytosine dioxygenase activity has been implicated in various diseases, including cancer, neurodevelopmental disorders, and cardiovascular disease. Understanding the molecular function of 5-methylcytosine dioxygenases is crucial for comprehending the role of DNA methylation in health and disease, and for developing novel therapeutic strategies targeting these enzymes.'
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| Protein | Definition | Taxonomy |
|---|---|---|
| Methylcytosine dioxygenase TET2 | A methylcytosine dioxygenase TET2 that is encoded in the genome of human. [PRO:DNx, UniProtKB:Q6N021] | Homo sapiens (human) |
| Compound | Definition | Classes | Roles |
|---|---|---|---|
| alpha-hydroxyglutarate | 2-hydroxyglutarate : A dicarboxylic acid anion obtained by deprotonation of at least one of the carboxy groups of 2-hydroxyglutaric acid. 2-hydroxyglutaric acid : A 2-hydroxydicarboxylic acid that is glutaric acid in which one hydrogen alpha- to a carboxylic acid group is substituted by a hydroxy group. | 2-hydroxydicarboxylic acid; dicarboxylic fatty acid | metabolite; mouse metabolite |
| deferoxamine | Deferoxamine: Natural product isolated from Streptomyces pilosus. It forms iron complexes and is used as a chelating agent, particularly in the mesylate form. desferrioxamine B : An acyclic desferrioxamine that is butanedioic acid in which one of the carboxy groups undergoes formal condensation with the primary amino group of N-(5-aminopentyl)-N-hydroxyacetamide and the second carboxy group undergoes formal condensation with the hydroxyamino group of N(1)-(5-aminopentyl)-N(1)-hydroxy-N(4)-[5-(hydroxyamino)pentyl]butanediamide. It is a siderophore native to Streptomyces pilosus biosynthesised by the DesABCD enzyme cluster as a high affinity Fe(III) chelator. | acyclic desferrioxamine | bacterial metabolite; ferroptosis inhibitor; iron chelator; siderophore |
| 5-carboxy-8-hydroxyquinoline | 5-carboxy-8-hydroxyquinoline: a JmjC histone demethylase inhibitor; structure in first source | quinolines | |
| oxalylglycine | N-oxalylglycine : An amino dicarboxylic acid that is iminodiacetic acid with an oxo substituent. It is used as an inhibitor of alpha-ketoglutarate dependent (EC 1.14.11.*) enzymes. oxalylglycine: structure given in first source | amino dicarboxylic acid; N-acylglycine | EC 1.14.11.* (oxidoreductase acting on paired donors, 2-oxoglutarate as one donor, incorporating 1 atom each of oxygen into both donors) inhibitor |