Target type: molecularfunction
Catalysis of the removal of a methyl group from a di or a monomethyl-lysine residue at position 9 of the histone H3 protein. This is a dioxygenase reaction that is dependent on Fe(II) and 2-oxoglutarate. [PMID:16603238]
Histone H3K9me/H3K9me2 demethylase activity refers to the enzymatic ability to remove methyl groups from lysine 9 of histone H3, specifically targeting the monomethylated (H3K9me) and dimethylated (H3K9me2) states. This activity is crucial for regulating chromatin structure and gene expression.
H3K9 methylation is a hallmark of heterochromatin, a densely packed state of chromatin that is generally transcriptionally inactive. Demethylation of H3K9me and H3K9me2 by demethylases can therefore lead to chromatin relaxation and gene activation.
Histone H3K9me/H3K9me2 demethylases play a critical role in various cellular processes, including:
- **Development:** Proper development relies on precise regulation of gene expression, which is influenced by histone methylation and demethylase activity.
- **Transcription:** Demethylation of H3K9me and H3K9me2 allows for the recruitment of transcription factors and the initiation of gene transcription.
- **DNA Repair:** Demethylases contribute to the recruitment of DNA repair machinery to damaged DNA sites.
- **Immune Response:** Demethylation of H3K9me and H3K9me2 can regulate the expression of genes involved in immune responses.
Several families of enzymes possess histone H3K9me/H3K9me2 demethylase activity, including:
- **Lysine-specific demethylases (LSD1/KDM1A and LSD2/KDM1B):** These enzymes utilize flavin adenine dinucleotide (FAD) as a cofactor and specifically remove monomethyl and dimethyl groups from H3K9.
- **Jumonji C (JmjC) domain-containing demethylases:** This family comprises a diverse group of enzymes that utilize iron and α-ketoglutarate as cofactors. Some JmjC demethylases specifically target H3K9me and H3K9me2, while others can also remove trimethylation (H3K9me3).
Dysregulation of histone H3K9me/H3K9me2 demethylase activity has been implicated in various diseases, including cancer and neurological disorders. Therefore, understanding the molecular function of these enzymes is crucial for developing therapeutic strategies to target specific diseases.'
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| Protein | Definition | Taxonomy |
|---|---|---|
| Lysine-specific demethylase 3A | A lysine-specific demethylase 3A that is encoded in the genome of human. [PRO:DNx, UniProtKB:Q9Y4C1] | 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 3B | A lysine-specific demethylase 3B that is encoded in the genome of human. [PRO:DNx, UniProtKB:Q7LBC6] | 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) |
| 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 |
| 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 | |
| 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 |
| 3-[[2-(2-pyridinyl)-6-(1,2,4,5-tetrahydro-3-benzazepin-3-yl)-4-pyrimidinyl]amino]propanoic acid | organonitrogen heterocyclic compound |