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Literature summary extracted from

  • El Mansouri, F.; Nebbaki, S.; Kapoor, M.; Afif, H.; Martel-Pelletier, J.; Pelletier, J.; Benderdour, M.; Fahmi, H.
    Lysine-specific demethylase 1-mediated demethylation of histone H3 lysine 9 contributes to interleukin 1beta-induced microsomal prostaglandin E synthase 1 expression in human osteoarthritic chondrocytes (2014), Arthritis Res. Ther., 16, R113 .
    View publication on PubMedView publication on EuropePMC

Activating Compound

EC Number Activating Compound Comment Organism Structure
1.14.11.65 additional information interleukin-1beta enhances recruitment of LSD1 to mPGES-1 promoter Homo sapiens
1.14.11.67 additional information interleukin-1beta enhances recruitment of LSD1 to mPGES-1 promoter Homo sapiens

Cloned(Commentary)

EC Number Cloned (Comment) Organism
1.14.11.65 gene KDM1A, real-time PCR enzyme expression analysis Homo sapiens
1.14.11.67 gene KDM1A, real-time PCR enzyme expression analysis Homo sapiens

Protein Variants

EC Number Protein Variants Comment Organism
1.14.11.65 additional information the enzyme is knocked out by expression of specific siRNA for LSD1 in chondrocytes Homo sapiens
1.14.11.67 additional information the enzyme is knocked out by expression of specific siRNA for LSD1 in chondrocytes Homo sapiens

Inhibitors

EC Number Inhibitors Comment Organism Structure
1.14.11.65 Pargyline
-
Homo sapiens
1.14.11.65 tranylcypromine
-
Homo sapiens
1.14.11.67 Pargyline
-
Homo sapiens
1.14.11.67 tranylcypromine
-
Homo sapiens

Localization

EC Number Localization Comment Organism GeneOntology No. Textmining
1.14.11.65 chromatin
-
Homo sapiens 785
-
1.14.11.65 mitochondrion enzyme LSD1 is present at the proximal region of the microsomal PGES-1 promoter Homo sapiens 5739
-
1.14.11.67 nucleus
-
Homo sapiens 5634
-

Metals/Ions

EC Number Metals/Ions Comment Organism Structure
1.14.11.65 Fe2+ required Homo sapiens
1.14.11.67 Fe2+ required Homo sapiens

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-lysine9 + 2-oxoglutarate + O2 Homo sapiens
-
histone H3 N6-methyl-L-lysine9 + succinate + formaldehyde + CO2
-
?
1.14.11.65 histone H3 N6-methyl-L-lysine9 + 2-oxoglutarate + O2 Homo sapiens
-
histone H3 L-lysine9 + succinate + formaldehyde + CO2
-
?
1.14.11.67 histone H3 N6,N6,N6-trimethyl-L-lysine4 + 2-oxoglutarate + O2 Homo sapiens
-
histone H3 N6,N6-dimethyl-L-lysine4 + succinate + formaldehyde + CO2
-
?
1.14.11.67 histone H3 N6,N6-dimethyl-L-lysine4 + 2-oxoglutarate + O2 Homo sapiens
-
histone H3 N6-methyl-L-lysine4 + succinate + formaldehyde + CO2
-
?

Organism

EC Number Organism UniProt Comment Textmining
1.14.11.65 Homo sapiens O60341
-
-
1.14.11.67 Homo sapiens O60341
-
-

Source Tissue

EC Number Source Tissue Comment Organism Textmining
1.14.11.65 chondrocyte osteoarthritic chondrocytes Homo sapiens
-
1.14.11.67 chondrocyte
-
Homo sapiens
-

Substrates and Products (Substrate)

EC Number Substrates Comment Substrates Organism Products Comment (Products) Rev. Reac.
1.14.11.65 histone H3 N6,N6-dimethyl-L-lysine9 + 2-oxoglutarate + O2
-
Homo sapiens histone H3 N6-methyl-L-lysine9 + succinate + formaldehyde + CO2
-
?
1.14.11.65 histone H3 N6-methyl-L-lysine9 + 2-oxoglutarate + O2
-
Homo sapiens histone H3 L-lysine9 + succinate + formaldehyde + CO2
-
?
1.14.11.65 additional information histone H3 N6,N6,N6-trimethyl-L-lysine9 is no substrate Homo sapiens ?
-
?
1.14.11.67 histone H3 N6,N6,N6-trimethyl-L-lysine4 + 2-oxoglutarate + O2
-
Homo sapiens histone H3 N6,N6-dimethyl-L-lysine4 + succinate + formaldehyde + CO2
-
?
1.14.11.67 histone H3 N6,N6-dimethyl-L-lysine4 + 2-oxoglutarate + O2
-
Homo sapiens histone H3 N6-methyl-L-lysine4 + succinate + formaldehyde + CO2
-
?

Synonyms

EC Number Synonyms Comment Organism
1.14.11.65 BHC110
-
Homo sapiens
1.14.11.65 KDM1A
-
Homo sapiens
1.14.11.65 LSD1
-
Homo sapiens
1.14.11.65 lysine-specific demethylase 1
-
Homo sapiens
1.14.11.65 NPAO
-
Homo sapiens
1.14.11.65 p110b
-
Homo sapiens
1.14.11.67 LSD1
-
Homo sapiens
1.14.11.67 lysine-specific demethylase 1
-
Homo sapiens

Cofactor

EC Number Cofactor Comment Organism Structure
1.14.11.65 FAD required, LSD1 utilizes FAD as an essential cofactor in catalyzing demethylation of mono- and di-methylated H3K9. Interleukin-1-induced H3K9 demethylation and LSD1 recruitment in human chondrocytes are not associated with significant changes in FAD levels Homo sapiens
1.14.11.67 FAD required Homo sapiens

General Information

EC Number General Information Comment Organism
1.14.11.65 evolution the enzyme belongs to the superfamily of flavin adenine dinucleotide (FAD)–dependent amine oxidases Homo sapiens
1.14.11.65 malfunction both pharmacological inhibition of LSD1 and small interfering RNA (siRNA) knockdown prevents interleukin 1beta-induced H3K9 demethylation at the mPGES-1 promoter as well as concomitant mPGES-1 protein expression. The level of LSD1 expression is elevated in osteoarthritis cartilage Homo sapiens
1.14.11.65 physiological function lysine-specific demethylase 1-mediated demethylation of histone H3 lysine 9 contributes to interleukin 1beta-induced microsomal prostaglandin E synthase 1 (mPGES-1) expression in human osteoarthritic chondrocytes. mPGES-1 catalyzes the terminal step in the biosynthesis of PGE2, a critical mediator in the pathophysiology of osteoarthritis. Histone methylation plays an important role in epigenetic gene regulation. LSD1 modulates gene expression through demethylation of either H3K4 or H3K9. H3K9 methylation usually suppresses transcription, whereas H3K4 methylation generally activates transcription. The induction of mPGES-1 expression by interleukin-1beta is associated with decreased levels of mono- and dimethylated H3K9, but not trimethylated H3K9, at the mPGES-1 promoter correlating with the recruitment of the histone demethylase LSD1 Homo sapiens
1.14.11.67 evolution the enzyme belongs to the superfamily of flavin adenine dinucleotide (FAD)-dependent amine oxidases Homo sapiens
1.14.11.67 malfunction both pharmacological inhibition of LSD1 and small interfering RNA (siRNA) knockdown prevents interleukin 1beta-induced H3K9 demethylation at the mPGES-1 promoter as well as concomitant mPGES-1 protein expression. The level of LSD1 expression is elevated in osteoarthritis cartilage Homo sapiens
1.14.11.67 physiological function LSD1 modulates gene expression through demethylation of either H3K4 or H3K9. H3K9 methylation usually suppresses transcription, whereas H3K4 methylation generally activates transcription. H3K4 methylation is a critical epigenetic marker of transcriptional activation. Lysine-specific demethylase 1-mediated demethylation of histone H3 lysine 9, but not lysine 4, contributes to interleukin 1beta-induced microsomal prostaglandin E synthase 1 (mPGES-1) expression in human osteoarthritic chondrocytes. Levels of di- and trimethylated H3K4 are significantly enhanced after 4 h of interleukin-1beta stimulation, reach a maximum at 12 h, persist through 24 h and decrease at 48 h. In contrast, the level of monomethylated H3K4 remain almost unchanged following interleukin-1beta stimulation. The increase in H3K4 di- and trimethylation by interleukin-1beta at the mPGES-1 promoter paralleles the increased transcription of mPGES-1, suggesting that, in addition to H3K9 demethylation, H3K4 methylation also contributes to interleukin-1beta-induced mPGES-1 expression, the induction of mPGES-1 by interleukin-1beta is associated with H3K4 methylation Homo sapiens