Target type: molecularfunction
Catalysis of the removal of a methyl group from a tri- or a dimethyl-lysine residue at position 27 of the histone H3 protein. This is a dioxygenase reaction that is dependent on Fe(II) and 2-oxoglutarate. [GOC:sp, PMID:20622853]
Histone H3K27me2/H3K27me3 demethylases are enzymes that remove methyl groups from lysine 27 of histone H3, a key regulatory modification in eukaryotic chromatin. These enzymes play a critical role in gene regulation by modulating the accessibility of DNA to transcription factors and other regulatory proteins.
H3K27 methylation is typically associated with gene silencing, and demethylases contribute to the activation of genes by removing the repressive mark. The removal of methyl groups from H3K27 can lead to a more open chromatin structure, allowing for the recruitment of transcription factors and the initiation of gene transcription.
There are two main families of H3K27me2/H3K27me3 demethylases:
* **KDM6 (JMJD3) family:** These demethylases are dioxygenases that use Fe(II) and 2-oxoglutarate as cofactors to catalyze the oxidative demethylation of H3K27. They are often involved in the regulation of developmental genes and are implicated in various diseases, including cancer.
* **KDM7 (PHF2) family:** This family also utilizes Fe(II) and 2-oxoglutarate as cofactors but differs in their catalytic mechanism and substrate specificity. KDM7 enzymes are known to demethylate both H3K27me2 and H3K27me3, but they may also target other histone lysine residues. They are associated with diverse cellular processes, including DNA repair, cell cycle control, and neuronal function.
The specific function of H3K27me2/H3K27me3 demethylases depends on the cellular context, the target gene, and the interplay with other regulatory factors. These enzymes are essential for proper gene expression and development, and their dysregulation can contribute to various diseases.'
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| Protein | Definition | Taxonomy |
|---|---|---|
| Lysine-specific demethylase 6A | A lysine-specific demethylase 6A that is encoded in the genome of human. [PRO:DNx, UniProtKB:O15550] | Homo sapiens (human) |
| Histone lysine demethylase PHF8 | A histone lysine demethylase PHF8 that is encoded in the genome of human. [PRO:DNx, UniProtKB:Q9UPP1] | Homo sapiens (human) |
| Lysine-specific demethylase 7A | A lysine-specific demethylase 7A that is encoded in the genome of human. [PRO:DNx, UniProtKB:Q6ZMT4] | Homo sapiens (human) |
| Lysine-specific demethylase 6B | A lysine-specific demethylase 6B that is encoded in the genome of human. [PRO:DNx, UniProtKB:O15054] | Homo sapiens (human) |
| Compound | Definition | Classes | Roles |
|---|---|---|---|
| amiodarone | amiodarone : A member of the class of 1-benzofurans that is 1-benzofuran substituted by a butyl group at position 2 and a 4-[2-(diethylamino)ethoxy]-3,5-diiodobenzoyl group at position 3. It is a cardiovascular drug used for the treatment of cardiac dysrhythmias. Amiodarone: An antianginal and class III antiarrhythmic drug. It increases the duration of ventricular and atrial muscle action by inhibiting POTASSIUM CHANNELS and VOLTAGE-GATED SODIUM CHANNELS. There is a resulting decrease in heart rate and in vascular resistance. | 1-benzofurans; aromatic ketone; organoiodine compound; tertiary amino compound | cardiovascular drug |
| deferiprone | deferiprone : A member of the class of 4-pyridones that is pyridin-4(1H)-one substituted at positions 1 and 2 by methyl groups and at position 3 by a hydroxy group. A lipid-soluble iron-chelator used for treatment of thalassaemia. Deferiprone: A pyridone derivative and iron chelator that is used in the treatment of IRON OVERLOAD in patients with THALASSEMIA. | 4-pyridones | iron chelator; protective agent |
| succinylacetone | 4,6-dioxoheptanoic acid : A dioxo monocarboxylic acid that is heptanoic acid in which oxo groups replace the hydrogens at positions 4 and 6. It is an abnormal metabolite of the tyrosine metabolic pathway and a marker for type 1 tyrosinaemia. succinylacetone: inhibitor of heme biosynthesis | beta-diketone; dioxo monocarboxylic acid | human metabolite |
| 2,4-pyridinedicarboxylic acid | lutidinic acid : A pyridinedicarboxylic acid carrying carboxy groups at positions 2 and 4. | pyridinedicarboxylic acid | |
| daminozide | daminozide: induces tumors | straight-chain fatty acid | |
| deferasirox | deferasirox : A member of the class of triazoles, deferasirox is 1,2,4-triazole substituted by a 4-carboxyphenyl group at position 1 and by 2-hydroxyphenyl groups at positions 3 and 5. An orally active iron chelator, it is used to manage chronic iron overload in patients receiving long-term blood transfusions. Deferasirox: A triazole and benzoate derivative that acts as a selective iron chelator. It is used in the management of chronic IRON OVERLOAD due to blood transfusion or non-transfusion dependent THALASSEMIA. | benzoic acids; monocarboxylic acid; phenols; triazoles | iron chelator |
| 5-carboxy-8-hydroxyquinoline | 5-carboxy-8-hydroxyquinoline: a JmjC histone demethylase inhibitor; structure in first source | quinolines | |
| (1R,2S)-tranylcypromine hydrochloride | (1R,2S)-tranylcypromine hydrochloride : A hydrochloride obtained by combining (1R,2S)-tranylcypromine with one equivalent of hydrochloric acid. | hydrochloride | |
| 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 |
| geldanamycin | 1,4-benzoquinones; ansamycin; carbamate ester; organic heterobicyclic compound | antimicrobial agent; antineoplastic agent; antiviral agent; cysteine protease inhibitor; Hsp90 inhibitor | |
| 17-(dimethylaminoethylamino)-17-demethoxygeldanamycin | 17-(dimethylaminoethylamino)-17-demethoxygeldanamycin: structure in first source alvespimycin : A 19-membered macrocyle that is geldanamycin in which the methoxy group attached to the benzoquinone moiety has been replaced by a 2-(N,N-dimethylamino)ethylamino group. | 1,4-benzoquinones; ansamycin; carbamate ester; secondary amino compound; tertiary amino compound | Hsp90 inhibitor |
| tanespimycin | CP 127374: analog of herbimycin A | 1,4-benzoquinones; ansamycin; carbamate ester; organic heterobicyclic compound; secondary amino compound | antineoplastic agent; apoptosis inducer; Hsp90 inhibitor |
| 3-[[2-(2-pyridinyl)-6-(1,2,4,5-tetrahydro-3-benzazepin-3-yl)-4-pyrimidinyl]amino]propanoic acid | organonitrogen heterocyclic compound | ||
| gsk-j4 | GSK-J4: a JMJD3 inhibitor; structure in first source | organonitrogen heterocyclic compound |