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Literature summary extracted from
- Inhibition of the histone demethylase LSD1 blocks alpha-herpesvirus lytic replication and reactivation from latency (2009), Nat. Med., 15, 1312-1317 .
Inhibitors
| EC Number | Inhibitors | Comment | Organism | Structure |
|---|---|---|---|---|
| 1.14.11.65 | HCF-1 | a component of the Set1 and MLL1 histone H3 Lys4 methyltransferase complexes, which coordinates modulation of repressive H3 Lys9 methylation levels with addition of activating H3 Lys4 trimethylation marks | Homo sapiens | |
| 1.14.11.65 | additional information | depletion of LSD1 or inhibition of its activity with monoamine oxidase inhibitors (MAOIs) results in the accumulation of repressive chromatin and a block to viral gene expression | Homo sapiens | |
| 1.14.99.66 | HCF-1 | a component of the Set1 and MLL1 histone H3 Lys4 methyltransferase complexes, which coordinates modulation of repressive H3 Lys9 methylation levels with addition of activating H3 Lys4 trimethylation marks | Homo sapiens | |
| 1.14.99.66 | additional information | depletion of LSD1 or inhibition of its activity with monoamine oxidase inhibitors (MAOIs) results in the accumulation of repressive chromatin and a block to viral gene expression | Homo sapiens |
Localization
| EC Number | Localization | Comment | Organism | GeneOntology No. | Textmining |
|---|---|---|---|---|---|
| 1.14.11.65 | nucleus | - |
Homo sapiens | 5634 | - |
| 1.14.99.66 | nucleus | - |
Homo sapiens | 5634 | - |
Natural Substrates/ Products (Substrates)
| EC Number | Natural Substrates | Organism | Comment (Nat. Sub.) | Natural Products | Comment (Nat. Pro.) | Rev. | Reac. |
|---|---|---|---|---|---|---|---|
| 1.14.11.65 | [histone H3]-N6,N6-dimethyl-L-lysine 9 + 2-oxoglutarate + O2 | Homo sapiens | - |
[histone H3]-N6-methyl-L-lysine 9 + succinate + formaldehyde + CO2 | - |
? |  |
| 1.14.11.65 | [histone H3]-N6-methyl-L-lysine 9 + 2-oxoglutarate + O2 | Homo sapiens | - |
[histone H3]-L-lysine 9 + succinate + formaldehyde + CO2 | - |
? | |
| 1.14.99.66 | [histone H3]-N6,N6-dimethyl-L-lysine 4 + 2-oxoglutarate + O2 | Homo sapiens | - |
[histone H3]-N6-methyl-L-lysine 4 + succinate + formaldehyde + CO2 | - |
? | |
| 1.14.99.66 | [histone H3]-N6-methyl-L-lysine 4 + 2-oxoglutarate + O2 | Homo sapiens | - |
[histone H3]-L-lysine 4 + succinate + formaldehyde + CO2 | - |
? | |
Organism
| EC Number | Organism | UniProt | Comment | Textmining |
|---|---|---|---|---|
| 1.14.11.65 | Homo sapiens | O60341 | - |
- |
| 1.14.99.66 | Homo sapiens | O60341 | - |
- |
Substrates and Products (Substrate)
| EC Number | Substrates | Comment Substrates | Organism | Products | Comment (Products) | Rev. | Reac. |
|---|---|---|---|---|---|---|---|
| 1.14.11.65 | additional information | the bifunctional enzyme catalyzes the demethylation of H3K9me2/me1 and H3K4me2/me1 (EC 1.14.99.66). As LSD1 can demethylate both H3K4 and H3K9, the coupling of this protein in the HCF-1-Set1 or MLL methyltransferase complex may enhance H3K9 demethylation or preferentially target it to this substrate, although additional histone modifications and modification activities may also contribute to the H3K4 or H3K9 recognition and specificity | Homo sapiens | ? | - |
? | |
| 1.14.11.65 | [histone H3]-N6,N6-dimethyl-L-lysine 9 + 2-oxoglutarate + O2 | - |
Homo sapiens | [histone H3]-N6-methyl-L-lysine 9 + succinate + formaldehyde + CO2 | - |
? | |
| 1.14.11.65 | [histone H3]-N6-methyl-L-lysine 9 + 2-oxoglutarate + O2 | - |
Homo sapiens | [histone H3]-L-lysine 9 + succinate + formaldehyde + CO2 | - |
? | |
| 1.14.99.66 | additional information | the bifunctional enzyme catalyzes the demethylation of H3K9me2/me1 (EC 1.14.11.65) and H3K4me2/me1. As LSD1 can demethylate both H3K4 and H3K9, the coupling of this protein in the HCF-1 Set1 or MLL methyltransferase complex may enhance H3K9 demethylation or preferentially target it to this substrate, although additional histone modifications and modification activities may also contribute to the H3K4 or H3K9 recognition and specificity | Homo sapiens | ? | - |
? | |
| 1.14.99.66 | [histone H3]-N6,N6-dimethyl-L-lysine 4 + 2-oxoglutarate + O2 | - |
Homo sapiens | [histone H3]-N6-methyl-L-lysine 4 + succinate + formaldehyde + CO2 | - |
? | |
| 1.14.99.66 | [histone H3]-N6-methyl-L-lysine 4 + 2-oxoglutarate + O2 | - |
Homo sapiens | [histone H3]-L-lysine 4 + succinate + formaldehyde + CO2 | - |
? | |
Synonyms
| EC Number | Synonyms | Comment | Organism |
|---|---|---|---|
| 1.14.11.65 | LSD1 | - |
Homo sapiens |
| 1.14.11.65 | More | see also for EC 1.14.99.66 | Homo sapiens |
| 1.14.99.66 | LSD1 | - |
Homo sapiens |
| 1.14.99.66 | More | see also for EC 1.14.11.65 | Homo sapiens |
General Information
| EC Number | General Information | Comment | Organism |
|---|---|---|---|
| 1.14.11.65 | malfunction | depletion of LSD1 or inhibition of its activity with monoamine oxidase inhibitors (MAOIs) results in the accumulation of repressive chromatin and a block to viral gene expression. HCF-1 depletion resulted in a concomitant decrease in the recruitment of LSD1 | Homo sapiens |
| 1.14.11.65 | physiological function | infection by the alpha-herpesviruses Herpes simplex virus and Varicella zoster virus results in the rapid accumulation of chromatin bearing repressive histone H3 Lys9 methylation. To enable expression of viral immediate early (IE) genes, both viruses use the cellular transcriptional coactivator host cell factor-1, HCF-1, to recruit the lysine-specific demethylase-1, LSD1, to the viral immediate early promoters. LSD1 has a role in viral IE62-mediated activation, LSD1 is crucial for IE gene expression during viral infection, HCF-1-LSD1 complex is essential for alpha-herpesvirus IE gene transcription. Reversible methylation of histone tails serves as either a positive signal recognized by transcriptional assemblies or a negative signal that result in repression. The H3K9 demethylase activity of LSD1 is crucial for nuclear hormone receptor-dependent transcription and cell fate determination, and LSD1 is crucial for viral activator-mediated transcription of herpes simplex virus and varicella zoster virus IE model promoters. As LSD1 can demethylate both H3K4 and H3K9, the coupling of this protein in the HCF-1-Set1 or MLL methyltransferase complex may enhance H3K9 demethylation or preferentially target it to this substrate, although additional histone modifications and modification activities may also contribute to the H3K4 or H3K9 recognition and specificity | Homo sapiens |
| 1.14.99.66 | malfunction | depletion of LSD1 or inhibition of its activity with monoamine oxidase inhibitors (MAOIs) results in the accumulation of repressive chromatin and a block to viral gene expression. HCF-1 depletion resulted in a concomitant decrease in the recruitment of LSD1 | Homo sapiens |
| 1.14.99.66 | physiological function | infection by the alpha-herpesviruses Herpes simplex virus and Varicella zoster virus results in the rapid accumulation of chromatin bearing repressive histone H3 Lys9 methylation. To enable expression of viral immediate early (IE) genes, both viruses use the cellular transcriptional coactivator host cell factor-1, HCF-1, to recruit the lysine-specific demethylase-1, LSD1, to the viral immediate early promoters. LSD1 has a role in viral IE62-mediated activation, LSD1 is crucial for IE gene expression during viral infection, HCF-1-LSD1 complex is essential for alpha-herpesvirus IE gene transcription. Reversible methylation of histone tails serves as either a positive signal recognized by transcriptional assemblies or a negative signal that result in repression. The H3K9 demethylase activity of LSD1 is crucial for nuclear hormone receptor-dependent transcription and cell fate determination, and LSD1 is crucial for viral activator-mediated transcription of herpes simplex virus and varicella zoster virus IE model promoters. As LSD1 can demethylate both H3K4 and H3K9, the coupling of this protein in the HCF-1 Set1 or MLL methyltransferase complex may enhance H3K9 demethylation or preferentially target it to this substrate, although additional histone modifications and modification activities may also contribute to the H3K4 or H3K9 recognition and specificity | Homo sapiens |
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