Information on EC 1.14.11.B2 - [histone-H3]-lysine-4-demethylase

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The enzyme appears in viruses and cellular organisms

EC NUMBER
COMMENTARY hide
1.14.11.B2
preliminary BRENDA-supplied EC number
RECOMMENDED NAME
GeneOntology No.
[histone-H3]-lysine-4-demethylase
-
REACTION
REACTION DIAGRAM
COMMENTARY hide
ORGANISM
UNIPROT
LITERATURE
protein N6,N6-dimethyl-L-lysine4 + 2-oxoglutarate + O2 = protein N6-methyl-L-lysine4 + succinate + formaldehyde + CO2
show the reaction diagram
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-
-
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ORGANISM
COMMENTARY hide
LITERATURE
UNIPROT
SEQUENCE DB
SOURCE
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UniProt
Manually annotated by BRENDA team
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-
-
Manually annotated by BRENDA team
gene MAL8P1.111
-
-
Manually annotated by BRENDA team
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-
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Manually annotated by BRENDA team
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UniProt
Manually annotated by BRENDA team
GENERAL INFORMATION
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
evolution
malfunction
metabolism
physiological function
additional information
SUBSTRATE
PRODUCT                       
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate) hide
LITERATURE
(Substrate)
COMMENTARY
(Product) hide
LITERATURE
(Product)
Reversibility
r=reversible
ir=irreversible
?=not specified
dimethyl-histone 3-Lys4 peptide + H2O
histone 3-Lys4 peptide + ?
show the reaction diagram
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amino acids 1-21 of histone 3
-
-
?
H3(1-20) K4-dimethylated peptide + 2-oxoglutarate + O2
H3(1-20) K4-monomethylated peptide + succinate + formaldehyde + CO2
show the reaction diagram
-
-
-
-
?
histone H3 N6,N6,N6-trimethyl-L-lysine4 + 2-oxoglutarate + O2
histone H3 N6,N6-dimethyl-L-lysine4 + succinate + formaldehyde + CO2
show the reaction diagram
histone H3 N6,N6-dimethyl-L-lysine4 + 2-oxoglutarate + O2
histone H3 N6-methyl-L-lysine4 + succinate + formaldehyde + CO2
show the reaction diagram
histone H3 N6,N6-dimethyl-L-lysine4 + 2-oxoglutarate + O2
histone H3 N6-methyl-L-lysine9 + succinate + formaldehyde + CO2
show the reaction diagram
-
-
-
?
histone H3 N6,N6-dimethyl-L-lysine4 peptide1-21 + 2-oxoglutarate + O2
histone H3 N6-methyl-L-lysine4 peptide1-21 + succinate + formaldehyde + CO2
show the reaction diagram
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minimal peptide substrate, binding of KDM1A to the peptide substrate H3K4me2_1-21 is electrostatic in nature
-
-
?
histone H3 N6-dimethyl-L-lysine4 + 2-oxoglutarate + O2
histone H3 L-lysine4 + succinate + formaldehyde + CO2
show the reaction diagram
-
-
-
?
histone H3 N6-methyl-L-lysine4 + 2-oxoglutarate + O2
histone H3 L-lysine4 + succinate + formaldehyde + CO2
show the reaction diagram
histone H3 N6-methyl-L-lysine4 peptide1-21 + 2-oxoglutarate + O2
histone H3 L-lysine4 peptide1-21 + succinate + formaldehyde + CO2
show the reaction diagram
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minimal peptide substrate, binding of KDM1A to the peptide substrate H3K4me1_1-21 is electrostatic in nature
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-
?
protein 6-N,6-N-dimethyl-L-lysine + 2-oxoglutarate + O2
protein 6-N-methyl-L-lysine + succinate + formaldehyde + CO2
show the reaction diagram
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LSD1 relieves repressive histone marks by demethylation of histone H3 at lysine 9, thereby leading to derepression of androgen receptor target genes
-
-
?
protein 6-N-methyl-L-lysine + 2-oxoglutarate + O2
protein L-lysine + succinate + formaldehyde + CO2
show the reaction diagram
-
LSD1 relieves repressive histone marks by demethylation of histone H3 at lysine 9, thereby leading to derepression of androgen receptor target genes
-
-
?
[chromodomain Y-like protein]-N6,N6,N6-trimethyl-L-lysine135 + 2-oxoglutarate + O2
?
show the reaction diagram
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-
-
-
?
[Cockayne syndrome group B protein]-N6,N6,N6-trimethyl-L-lysine1054 + 2-oxoglutarate + O2
?
show the reaction diagram
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-
-
-
?
[Cockayne syndrome group B protein]-N6,N6,N6-trimethyl-L-lysine170 + 2-oxoglutarate + O2
?
show the reaction diagram
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-
-
-
?
[Cockayne syndrome group B protein]-N6,N6,N6-trimethyl-L-lysine297 + 2-oxoglutarate + O2
?
show the reaction diagram
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-
-
-
?
[Cockayne syndrome group B protein]-N6,N6,N6-trimethyl-L-lysine448 + 2-oxoglutarate + O2
?
show the reaction diagram
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-
-
-
?
[Dnmt1]-methyl-L-lysine + 2-oxoglutarate + O2
[Dnmt1]-L-lysine + succinate + formaldehyde + CO2
show the reaction diagram
[Dnmt1]-methyl-L-lysine-1096 + 2-oxoglutarate + O2
[Dnmt1]-L-lysine-1096 + succinate + formaldehyde + CO2
show the reaction diagram
-
human substrate protein, demethylation of the non-histone substrate at the Set7/9 methylation site Lys1096. Dnmt1, which contains over 120 lysine residues, seems to be methylated at multiple sites, as metabolic labeling experiments reveal that mutating K1096 in mouse Dnmt1 slightly reduces, but does not abolish, Dnmt1 methylation. Probably methylation at other sites is also involved in the regulation of Dnmt1 stability
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-
?
[Dnmt1]-methyl-L-lysine1096 + 2-oxoglutarate + O2
[Dnmt1]-L-lysine1096 + succinate + formaldehyde + CO2
show the reaction diagram
-
mechanistic link between the histone and DNA methylation systems
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-
?
[G9a protein]-N6,N6,N6-trimethyl-L-lysine185 + 2-oxoglutarate + O2
?
show the reaction diagram
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a customer synthesized protein
-
-
?
[histone H3]-N6,N6,N6-trimethyl-L-lysine9 + 2-oxoglutarate + O2
[histone H3]-L-lysine9 + succinate + formaldehyde + CO2
show the reaction diagram
[histone H3]-N6,N6-dimethyl-L-lysine36 + 2-oxoglutarate + O2
[histone H3]-L-lysine36 + succinate + formaldehyde + CO2
show the reaction diagram
[histone H3]-N6,N6-dimethyl-L-lysine9 + 2-oxoglutarate + O2
[histone H3]-L-lysine9 + succinate + formaldehyde + CO2
show the reaction diagram
[histone H3]-N6-methyl-L-lysine9 + 2-oxoglutarate + O2
[histone H3]-L-lysine9 + succinate + formaldehyde + CO2
show the reaction diagram
-
-
-
-
?
[histone-H3]-dimethyllysine4 + 2-oxoglutarate + O2
?
show the reaction diagram
[histone-H3]-tridimethyllysine4 + 2-oxoglutarate + O2
?
show the reaction diagram
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RBP2 is a demethylase that specifically catalyzes demethylation. RBP2 displayes robust H3K4 demethylase activity against H3K4me3 and me2, resulting in 80%-90% demethylation of the modified substrate, but fails to catalyze removal of the me1 modification state. The enzyme is capable of processively demethylating the H3K4me3 and me2 modifications to the unmodified state
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-
?
[histone-H3]-trimethyllysine4 + 2-oxoglutarate + O2
?
show the reaction diagram
[p53]-methyl-L-lysine + 2-oxoglutarate + O2
[p53]-L-lysine + succinate + formaldehyde + CO2
show the reaction diagram
[widely interspaced zinc finger motifs protein]-N6,N6,N6-trimethyl-L-lysine305 + 2-oxoglutarate + O2
?
show the reaction diagram
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-
-
-
?
additional information
?
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NATURAL SUBSTRATES
NATURAL PRODUCTS
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate) hide
LITERATURE
(Substrate)
COMMENTARY
(Product) hide
LITERATURE
(Product)
REVERSIBILITY
r=reversible
ir=irreversible
?=not specified
histone H3 N6,N6,N6-trimethyl-L-lysine4 + 2-oxoglutarate + O2
histone H3 N6,N6-dimethyl-L-lysine4 + succinate + formaldehyde + CO2
show the reaction diagram
histone H3 N6,N6-dimethyl-L-lysine4 + 2-oxoglutarate + O2
histone H3 N6-methyl-L-lysine4 + succinate + formaldehyde + CO2
show the reaction diagram
histone H3 N6-dimethyl-L-lysine4 + 2-oxoglutarate + O2
histone H3 L-lysine4 + succinate + formaldehyde + CO2
show the reaction diagram
P29375, Q9BY66, Q9UGL1
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-
-
?
histone H3 N6-methyl-L-lysine4 + 2-oxoglutarate + O2
histone H3 L-lysine4 + succinate + formaldehyde + CO2
show the reaction diagram
protein 6-N,6-N-dimethyl-L-lysine + 2-oxoglutarate + O2
protein 6-N-methyl-L-lysine + succinate + formaldehyde + CO2
show the reaction diagram
-
LSD1 relieves repressive histone marks by demethylation of histone H3 at lysine 9, thereby leading to derepression of androgen receptor target genes
-
-
?
protein 6-N-methyl-L-lysine + 2-oxoglutarate + O2
protein L-lysine + succinate + formaldehyde + CO2
show the reaction diagram
-
LSD1 relieves repressive histone marks by demethylation of histone H3 at lysine 9, thereby leading to derepression of androgen receptor target genes
-
-
?
[Dnmt1]-methyl-L-lysine + 2-oxoglutarate + O2
[Dnmt1]-L-lysine + succinate + formaldehyde + CO2
show the reaction diagram
-
LSD1 demethylates the protein and regulates its function
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-
?
[Dnmt1]-methyl-L-lysine1096 + 2-oxoglutarate + O2
[Dnmt1]-L-lysine1096 + succinate + formaldehyde + CO2
show the reaction diagram
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mechanistic link between the histone and DNA methylation systems
-
-
?
[histone H3]-N6,N6,N6-trimethyl-L-lysine9 + 2-oxoglutarate + O2
[histone H3]-L-lysine9 + succinate + formaldehyde + CO2
show the reaction diagram
[histone H3]-N6,N6-dimethyl-L-lysine36 + 2-oxoglutarate + O2
[histone H3]-L-lysine36 + succinate + formaldehyde + CO2
show the reaction diagram
-
-
-
-
?
[histone H3]-N6,N6-dimethyl-L-lysine9 + 2-oxoglutarate + O2
[histone H3]-L-lysine9 + succinate + formaldehyde + CO2
show the reaction diagram
[histone H3]-N6-methyl-L-lysine9 + 2-oxoglutarate + O2
[histone H3]-L-lysine9 + succinate + formaldehyde + CO2
show the reaction diagram
-
-
-
-
?
[histone-H3]-dimethyllysine4 + 2-oxoglutarate + O2
?
show the reaction diagram
[histone-H3]-tridimethyllysine4 + 2-oxoglutarate + O2
?
show the reaction diagram
-
RBP2 is a demethylase that specifically catalyzes demethylation. RBP2 displayes robust H3K4 demethylase activity against H3K4me3 and me2, resulting in 80%-90% demethylation of the modified substrate, but fails to catalyze removal of the me1 modification state. The enzyme is capable of processively demethylating the H3K4me3 and me2 modifications to the unmodified state
-
-
?
[histone-H3]-trimethyllysine4 + 2-oxoglutarate + O2
?
show the reaction diagram
[p53]-methyl-L-lysine + 2-oxoglutarate + O2
[p53]-L-lysine + succinate + formaldehyde + CO2
show the reaction diagram
-
LSD1 demethylates the protein and regulates its function
-
-
?
additional information
?
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COFACTOR
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
additional information
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LSD1 recruitment to sites of DNA damage is dependent on E3 ligase RNF168, RNF168 interacts with LSD1, overview. Rapid, transient recruitment of RNF168 to damage sites is H2A.X independent
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METALS and IONS
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
Iron
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iron-dependent dioxygenase
INHIBITORS
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
(12E)-N,N'-diethyl-5,10,16,21-tetraazapentacos-12-ene-1,25-diamine
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(13Z)-N,N'-diethyl-6,11,16,21-tetraazahexacos-13-ene-1,26-diamine
-
-
(19E)-N,N'-diethyl-6,12,17,22,27,33-hexaazaoctatriacont-19-ene-1,38-diamine
-
-
(19Z)-N,N'-diethyl-6,12,17,22,27,33-hexaazaoctatriacont-19-ene-1,38-diamine
-
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(2-hydroxyacetyl)-L-alanyl-L-arginyl-L-threonyl-L-methionyl-L-glutaminyl-L-threonyl-L-alanyl-L-arginyl-L-lysyl-L-seryl-L-threonylglycylglycyl-L-lysyl-L-alanyl-L-prolyl-L-arginyl-L-lysyl-L-glutaminyl-L-leucine
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(2-hydroxyacetyl)-L-arginyl-L-threonyl-L-methionyl-L-glutaminyl-L-threonyl-L-alanyl-L-arginyl-L-lysyl-L-seryl-L-threonylglycylglycyl-L-lysyl-L-alanyl-L-prolyl-L-arginyl-L-lysyl-L-glutaminyl-L-leucine
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(25E)-N,N'-diethyl-5,11,17,23,28,33,39,45-octaazapentacont-25-ene-1,50-diamine
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(25Z)-N,N'-diethyl-6,12,18,23,28,33,39,45-octaazapentacont-25-ene-1,50-diamine
-
-
(2Z)-N-ethyl-N'-[4-[(4-[[(2Z)-4-(ethylamino)but-2-en-1-yl]amino]butyl)amino]butyl]but-2-ene-1,4-diamine
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(2Z)-N-[4-(ethylamino)butyl]-N'-(4-[[4-(ethylamino)butyl]amino]butyl)but-2-ene-1,4-diamine
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(R)-2-(1-(1-benzoylpiperidin-3-yl)-1H-1,2,3-triazol-4-yl)isonicotinic acid
-
;
1,11-bis-[3-[1-(1,1-diphenylmethyl)thioureado]]-4,8-diazaundecane
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48.9% inhibition at 0.01 mM
1,11-bis-[3-[1-(2,2-diphenylethyl)thioureado]]-4,8-diazaundecane
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75.2% inhibition at 0.01 mM
1,11-bis-[3-[1-(3,3-diphenylpropyl)thioureado]]-4,8-diazaundecane
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7.8% inhibition at 0.01 mM
1,11-bis-[3-[1-(3,3-diphenylpropyl)ureado]]-4,8-diazaundecane
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7.1% inhibition at 0.01 mM
1,11-bis-[3-[1-(benzyl)thioureado]]-4,8-diazaundecane
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47.9% inhibition at 0.01 mM
1,11-bis-[3-[1-(benzyl)ureado]]-4,8-diazaundecane
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39.5% inhibition at 0.01 mM
1,11-bis-[3-[1-(ethyl)thioureado]]-4,8-diazaundecane
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63.8% inhibition at 0.01 mM
1,11-bis-[3-[1-(ethyl)ureado]]-4,8-diazaundecane
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34.5% inhibition at 0.01 mM
1,11-bis-[3-[1-(n-propyl)ureado]]-4,8-diazaundecane
-
; 48.7% inhibition at 0.01 mM
1,11-bis-[5-[1-(N,N-diphenyl)carbamyl]ureado]-4,8-diazaundecane
-
8.5% inhibition at 0.01 mM
1,12-bis-[3-[1-(1,1-diphenylmethyl)thioureado]]-4,9-diazadodecane
-
65.6% inhibition at 0.01 mM
1,12-bis-[3-[1-(2,2-diphenylethyl)thioureado]]-4,9-diazadodecane
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82.9% inhibition at 0.01 mM
1,12-bis-[3-[1-(3,3-diphenylpropyl)thioureado]]-4,9-diazadodecane
-
21.4% inhibition at 0.01 mM
1,12-bis-[3-[1-(3,3-diphenylpropyl)ureado]]-4,9-diazadodecane
-
25.4% inhibition at 0.01 mM
1,12-bis-[3-[1-(benzyl)ureado]]-4,9-diazadodecane
-
50.5% inhibition at 0.01 mM
1,12-bis-[3-[1-(ethyl)thioureado]]-4,9-diazadodecane
-
60% inhibition at 0.01 mM
1,12-bis-[3-[1-(ethyl)ureado]]-4,9-diazadodecane
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50.8% inhibition at 0.01 mM
1,12-bis-[3-[1-(n-propyl)thioureado]]-4,9-diazadodecane
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10.4% inhibition at 0.01 mM
1,12-bis-[3-[1-(n-propyl)ureado]]-4,9-diazadodecane
-
21% inhibition at 0.01 mM
1,12-bis-[5-[1-(N,N-diphenyl)carbamyl]ureado]-4,9-diazadodecane
-
73.9% inhibition at 0.01 mM
1,15-bis-[3-[1-(1,1-diphenylmethyl)thioureado]]-4,12-diazapentadecane
-
71.1% inhibition at 0.01 mM
1,15-bis-[3-[1-(2,2-diphenylethyl)thioureado]]-4,12-diazapentadecane
-
80.5% inhibition at 0.01 mM
1,15-bis-[3-[1-(3,3-diphenylpropyl)thioureado]]-4,12-diazapentadecane
-
22.7% inhibition at 0.01 mM
1,15-bis-[3-[1-(3,3-diphenylpropyl)ureado]]-4,12-diazapentadecane
-
48.5% inhibition at 0.01 mM
1,15-bis-[3-[1-(benzyl)thioureado]]-4,12-diazapentadecane
-
64.1% inhibition at 0.01 mM
1,15-bis-[3-[1-(benzyl)ureado]]-4,12-diazapentadecane
-
-
1,15-bis-[3-[1-(ethyl)ureado]]-4,12-diazapentadecane
-
-
1,15-bis-[3-[1-(n-propyl)ureado]]-4,12-diazapentadecane
-
8.5% inhibition at 0.01 mM
1,15-bis-[5-[1-(N,N-diphenyl)carbamyl]ureado]-4,12-diazapentadecane
-
30.0% inhibition at 0.01 mM
1,2-dimethyl-3-[(13E)-13-(methylamino)-4,8,12,14-tetraazapentadec-13-en-1-yl]guanidine
-
1 mM, about 80% inhibition. Inhibition affects a reexpression of multiple, aberrantly silenced genes important in the develoment of colon cancer. Reexpression is concurrent with increased dimethylated histone 3 lysine 4 and acetyl-histone 3 lysine 4 marks
1-(2,2-diphenylethyl)-3-(14-imino-17,17-diphenyl-4,9,13,15-tetraazaheptadec-1-yl)guanidine
-
1 mM, about 55% inhibition. Inhibition affects a reexpression of multiple, aberrantly silenced genes important in the develoment of colon cancer. Reexpression is concurrent with increased dimethylated histone 3 lysine 4 and acetyl-histone 3 lysine 4 marks
1-(3,3-diphenylpropyl)-3-(14-imino-18,18-diphenyl-4,9,13,15-tetraazaoctadec-1-yl)guanidine
-
1 mM, about 60% inhibition. Inhibition affects a reexpression of multiple, aberrantly silenced genes important in the develoment of colon cancer. Reexpression is concurrent with increased dimethylated histone 3 lysine 4 and acetyl-histone 3 lysine 4 marks
1-(3-(ethylsulfonyl)phenyl)-2-(4-(pyridin-2-yl)thiazol-2-yl)ethan-1-one
-
;
1-(3-(methylsulfonyl)phenyl)-2-(4-(pyridin-2-yl)thiazol-2-yl)ethan-1-one
-
;
1-(4-(methylsulfonyl)phenyl)-2-(4-(pyridin-2-yl)thiazol-2-yl)ethan-1-one
-
;
1-phenyl-2-(4-(pyridin-2-yl)thiazol-2-yl)ethan-1-one
-
;
2-(((2-((2-(dimethylamino)ethyl)(ethyl)amino)-2-oxoethyl)amino)methyl)-N-ethylisonicotinamide
-
2-(((2-((2-(dimethylamino)ethyl)(ethyl)amino)-2-oxoethyl)amino)methyl)-N-methylisonicotinamide
-
2-(((2-((2-(dimethylamino)ethyl)(ethyl)amino)-2-oxoethyl)amino)methyl)isonicotinamide
; the potent and selective KDM5A-D inhibitor stops cellular demethylation of H3K4me3 at transcription start sites and proliferation of MM1S myeloma cells; the potent and selective KDM5A-D inhibitor stops cellular demethylation of H3K4me3 at transcription start sites and proliferation of MM1S myeloma cells; the potent and selective KDM5A-D inhibitor stops cellular demethylation of H3K4me3 at transcription start sites and proliferation of MM1S myeloma cells. Analysis of enzyme-inhibitor binding structure from crystal structure analysis, overview
2-(((2-((2-(dimethylamino)ethyl)(ethyl)amino)-2-oxoethyl)amino)methyl)isonicotinic acid
-
2-(1-hydroxyvinyl)isonicotinic acid
-
;
2-(2-aminothiazol-4-yl)isonicotinamide
-
;
2-(2-aminothiazol-4-yl)isonicotinic acid
-
;
2-(2-benzamidothiazol-4-yl)isonicotinic acid
-
;
2-(2-methylthiazol-4-yl)isonicotinic acid
-
;
2-(piperazin-1-ylmethyl)isonicotinic acid
; the potent and selective KDM5A-D inhibitor stops cellular demethylation of H3K4me3 at transcription start sites and proliferation of MM1S myeloma cells
2-(thiazol-4-yl)isonicotinic acid
-
;
3,8,13,18,23-pentaazapentacosan-1-ol
-
-
3-((2-(pyridin-2-yl)-6-(1,2,4,5-tetrahydro-3H-benzo[d]azepin-3-yl)pyrimidin-4-yl)amino)propanoic acid
-
;
3-(2-((2-aminoethyl)carbamoyl)pyridin-4-yl)benzoic acid
-
;
3-(methylsulfonyl)-N-(4-(pyridin-3-yl)thiazol-2-yl)benzamide
-
;
4-((methyl((1-(4-oxo-3,4-dihydropyrido[3,4-d]pyrimidin-8-yl)-1H-pyrazol-4-yl)methyl)amino)methyl)benzonitrile
-
-
4-((methyl(2-(1-(4-oxo-3,4-dihydropyrido[3,4-d]pyrimidin-8-yl)-1H-pyrazol-4-yl)ethyl)amino)methyl)benzonitrile
-
-
4-(1-(2-(1-(4-oxo-3,4-dihydropyrido[3,4-d]pyrimidin-8-yl)-1H-pyrazol-4-yl)ethyl)piperidin-4-yl)benzonitrile
-
;
4-(methylsulfonyl)-N-(4-(pyridin-3-yl)thiazol-2-yl)benzamide
-
;
4-(pyridin-3-yl)thiazol-2-amine
-
;
8-(((furan-2-ylmethyl)amino)methyl)pyrido[3,4-d]pyrimidin-4(3H)-one
-
;
8-((4-(pyridin-2-yl)piperazin-1-yl)methyl)pyrido[3,4-d]pyrimidin-4(3H)-one
-
;
8-((4-methylpiperazin-1-yl)methyl)pyrido[3,4-d]pyrimidin-4(3H)-one
-
;
8-((4-phenylpiperazin-1-yl)methyl)pyrido[3,4-d]pyrimidin-4(3H)-one
-
-
8-((benzylamino)methyl)pyrido[3,4-d]pyrimidin-4(3H)-one
-
;
8-((dimethylamino)methyl)pyrido[3,4-d]pyrimidin-4(3H)-one
-
;
8-(1-methyl-1H-pyrazol-3-yl)pyrido[3,4-d]pyrimidin-4(3H)-one
-
;
8-(1H-pyrazol-1-yl)pyrido[3,4-d]pyrimidin-4(3H)-one
-
;
8-(1H-pyrazol-3-yl)pyrido[3,4-d]pyrimidin-4(3H)-one
-
;
8-(2-aminothiazol-4-yl)pyrido[3,4-d]pyrimidin-4(3H)-one
-
;
8-(4-(((3,4-dichlorobenzyl)(methyl)amino)methyl)-1H-pyrazol-1-yl)pyrido[3,4-d]pyrimidin-4(3H)-one
-
;
8-(4-((dimethylamino)methyl)-1H-pyrazol-1-yl)pyrido[3,4-d]pyrimidin-4(3H)-one
-
;
8-(4-((methyl(4-(methylsulfonyl)benzyl)amino)methyl)-1H-pyrazol-1-yl)pyrido[3,4-d]pyrimidin-4(3H)-one
-
-
8-(4-((methyl(4-(methylsulfonyl)benzyl)amino)methyl)-1H-pyrazol-1-yl)pyrido[3,4-d]pyrimidin-4(3H)-one52g
-
-
-
8-(4-(2-((4-fluorobenzyl) (methyl)amino)ethyl)-1H-pyrazol-1-yl)pyrido[3,4-d]pyrimidin-4(3H)-one
-
;
8-(4-(2-(4-((5-cyclopropyl-1,2,4-oxadiazol-3-yl)methyl)piperidin-1-yl)ethyl)-1H-pyrazol-1-yl)pyrido[3,4-d]pyrimidin-4(3H)-one
-
;
8-(4-(2-(4-(2,4-difluorophenyl)piperidin-1-yl)ethyl)-1H-pyrazol-1-yl)pyrido[3,4-d]pyrimidin-4(3H)-one
-
;
8-(4-(2-(4-(2-chlorophenyl)piperidin-1-yl)ethyl)-1H-pyrazol-1-yl)pyrido[3,4-d]pyrimidin-4(3H)-one
-
;
8-(4-(2-(4-(3,4-dichlorobenzyl)piperidin-1-yl)ethyl)-1H-pyrazol-1-yl)pyrido[3,4-d]pyrimidin-4(3H)-one
-
;
8-(4-(2-(4-(3,5-dichlorophenyl)piperidin-1-yl)ethyl)-1H-pyrazol-1-yl)pyrido[3,4-d]pyrimidin-4(3H)-one
-
; substitution from C4 of the pyrazole moiety allows access to the histone peptide substrate binding site, incorporation of a conformationally constrained 4-phenylpiperidine linker gives derivatives such as 8-(4-(2-(4-(3-chlorophenyl)piperidin-1-yl)ethyl)-1H-pyrazol-1-yl)pyrido[3,4-d]pyrimidin-4(3H)-one which demonstrates equipotent activity versus the KDM4 (JMJD2) and KDM5 (JARID1) subfamily demethylases, selectivity over representative exemplars of the KDM2, KDM3, and KDM6 subfamilies, and cellular permeability in the Caco-2 assay
8-(4-(2-(4-(3,5-difluorophenyl)piperidin-1-yl)ethyl)-1H-pyrazol-1-yl)pyrido[3,4-d]pyrimidin-4(3H)-one
-
;
8-(4-(2-(4-(3-(trifluoromethyl)phenyl)piperidin-1-yl)ethyl)-1H-pyrazol-1-yl)pyrido[3,4-d]pyrimidin-4(3H)-one
-
;
8-(4-(2-(4-(3-chlorophenyl)piperidin-1-yl)ethyl)-1H-pyrazol-1-yl)pyrido[3,4-d]pyrimidin-4(3H)-one
-
; substitution from C4 of the pyrazole moiety allows access to the histone peptide substrate binding site, incorporation of a conformationally constrained 4-phenylpiperidine linker gives derivatives such as 8-(4-(2-(4-(3-chlorophenyl)piperidin-1-yl)ethyl)-1H-pyrazol-1-yl)pyrido[3,4-d]pyrimidin-4(3H)-one which demonstrates equipotent activity versus the KDM4 (JMJD2) and KDM5 (JARID1) subfamily demethylases, selectivity over representative exemplars of the KDM2, KDM3, and KDM6 subfamilies, cellular permeability in the Caco-2 assay, and inhibition of H3K9Me3 and H3K4Me3 demethylation in a cell-based assay
8-(4-(2-(4-(3-methoxybenzyl)piperidin-1-yl)ethyl)-1H-pyrazol-1-yl)pyrido[3,4-d]pyrimidin-4(3H)-one
-
;
8-(4-(2-(4-(4-(methylsulfonyl)phenyl)piperidin-1-yl)ethyl)-1H-pyrazol-1-yl)pyrido[3,4-d]pyrimidin-4(3H)-one
-
;
8-(4-(2-(4-(4-(trifluoromethyl)benzyl)piperidin-1-yl)ethyl)-1H-pyrazol-1-yl)pyrido[3,4-d]pyrimidin-4(3H)-one
-
;
8-(4-(2-(4-(4-chlorobenzyl)piperidin-1-yl)ethyl)-1H-pyrazol-1-yl)pyrido[3,4-d]pyrimidin-4(3H)-one
-
;
8-(4-(2-(4-(4-chlorophenyl)piperidin-1-yl)ethyl)-1H-pyrazol-1-yl)pyrido[3,4-d]pyrimidin-4(3H)-one
-
;
8-(4-(2-(4-(4-fluorobenzyl)piperidin-1-yl)ethyl)-1H-pyrazol-1-yl)pyrido[3,4-d]pyrimidin-4(3H)-one
-
;
8-(4-(2-(4-(4-fluorophenyl)piperidin-1-yl)ethyl)-1H-pyrazol-1-yl)pyrido[3,4-d]pyrimidin-4(3H)-one
-
;
8-(4-(2-(4-(4-methoxyphenyl)piperidin-1-yl)ethyl)-1H-pyrazol-1-yl)pyrido[3,4-d]pyrimidin-4(3H)-one
-
;
8-(4-(2-(4-(benzo[d][1,3]dioxol-5-ylmethyl)piperidin-1-yl)ethyl)-1H-pyrazol-1-yl)pyrido[3,4-d]pyrimidin-4(3H)-one
-
;
8-(4-(2-(4-(pyridin-3-ylmethyl)piperidin-1-yl)ethyl)-1H-pyrazol-1-yl)pyrido[3,4-d]pyrimidin-4(3H)-one
-
;
8-(4-(2-(4-(pyridin-4-yl)piperidin-1-yl)ethyl)-1H-pyrazol-1-yl)pyrido[3,4-d]pyrimidin-4(3H)-one
-
;
8-(4-(2-(4-(thiophen-2-yl)piperidin-1-yl)ethyl)-1H-pyrazol-1-yl)pyrido[3,4-d]pyrimidin-4(3H)-one
-
;
8-(4-(2-(4-benzylpiperidin-1-yl)ethyl)-1H-pyrazol-1-yl)pyrido[3,4-d]pyrimidin-4(3H)-one
-
;
8-(4-(2-(4-phenylpiperidin-1-yl)ethyl)-1H-pyrazol-1-yl)pyrido[3,4-d]pyrimidin-4(3H)-one
-
;
8-(4-(hydroxymethyl)-1H-pyrazol-1-yl)pyrido[3,4-d]pyrimidin-4(3H)-one
-
;
8-(4-(piperidin-1-ylmethyl)-1H-pyrazol-1-yl)pyrido[3,4-d]pyrimidin-4(3H)-one
-
;
8-(4-(pyrrolidin-1-ylmethyl)-1H-pyrazol-1-yl)pyrido[3,4-d]pyrimidin-4(3H)-one
-
;
8-(piperidin-1-ylmethyl)pyrido[3,4-d]pyrimidin-4(3H)-one
-
;
8-(thiazol-4-yl)pyrido[3,4-d]pyrimidin-4(3H)-one
-
;
8-chloropyrido[3,4-d]pyrimidin-4(3H)-one
-
;
bis-[3-[1-(benzyl)thioureado]]-4,9-diazadodecane
-
25.2% inhibition at 0.01 mM
Cd2+
-
at 0.001-0.005 mM, cadmium increases global histone H3 methylation, H3K4me3 and H3K9me2, by inhibiting the activities of histone demethylases, and aberrant histone methylation that occurs early (48 h) and at 4 weeks is associated with cadmium-induced transformation of BEAS-2B cells at the early stage
Co2+
-
cobalt ions increase H3K9me3 and H3K36me3 by inhibiting histone demethylation process. cobalt ions do not affect JMJD2A protein level but directly inhibit its demethylase activity. Exposure of both lung carcinoma A549 cells and bronchial epithelial Beas-2B cells, to CoCl2 at 0.2 mM for 24 h increases methylation of histone H3 lysine residues 4, 9, 27 and 36, i.e. H3K4me3, H3K9me2, H3K9me3, H3K27me3, H3K36me3, as well as ubiquitination of histone H2A and H2B, while it decreases acetylation at histone H4, overview
ethyl 2-(((2-((2-(dimethylamino)ethyl)(ethyl)amino)-2-oxoethyl)amino)methyl)isonicotinate
-
GSK-J1
-
a selective inhibitor of the KDM6/KDM5 subfamilies. Docking study and identification of critical residues for binding of the inhibitor to the reconstituted KDM5 Jumonji domain; a selective inhibitor of the KDM6/KDM5 subfamilies. Docking study and identification of critical residues for binding of the inhibitor to the reconstituted KDM5 Jumonji domain. GSK-J1 inhibits the demethylase activity of KDM5C with 8.5fold increased potency compared with that of KDM5B at 1 mM 2-oxoglutarate. Also inhibits the enzyme mutant KDM5BDELTAAP; a selective inhibitor of the KDM6/KDM5 subfamilies. Docking study and identification of critical residues for binding of the inhibitor to the reconstituted KDM5 Jumonji domain. GSK-J1 inhibits the demethylase activity of KDM5C with 8.5fold increased potency compared with that of KDM5B at 1 mM 2-oxoglutarate. Also inhibits the enzyme mutant KDM5CDELTAAP
-
histone H3
-
full-length histone H3, H3_1-135, which lacks any posttranslational modifications, is a tight-binding, competitive inhibitor of KDM1A demethylation activity. Full-length H3 rapidly reaches equilibrium with KDM1A and shows 100fold increased binding affinity compared to a 21-mer H3-derived peptide
-
JIB-04
-
a pan-inhibitor of the Jumonji demethylase superfamily; a pan-inhibitor of the Jumonji demethylase superfamily, that is about 8fold more potent against KDM5B than against KDM5C. Also inhibits the enzyme mutant KDM5BDELTAAP; a pan-inhibitor of the Jumonji demethylase superfamily, that is about 8fold more potent against KDM5B than against KDM5C. Also inhibits the enzyme mutant KDM5CDELTAAP
-
L-alanyl-L-arginyl-L-threonyl-L-methionyl-L-glutaminyl-L-threonyl-L-alanyl-L-arginyl-L-lysyl-L-seryl-L-threonylglycylglycyl-L-lysyl-L-alanyl-L-prolyl-L-arginyl-L-lysyl-L-glutaminyl-L-leucine
-
-
L-arginyl-L-threonyl-L-methionyl-L-glutaminyl-L-threonyl-L-alanyl-L-arginyl-L-lysyl-L-seryl-L-threonylglycylglycyl-L-lysyl-L-alanyl-L-prolyl-L-arginyl-L-lysyl-L-glutaminyl-L-leucine
-
-
L-homoseryseryl-L-arginyl-L-threonyl-L-methionyl-L-glutaminyl-L-threonyl-L-alanyl-L-arginyl-L-lysyl-L-seryl-L-threonylglycylglycyl-L-lysyl-L-alanyl-L-prolyl-L-arginyl-L-lysyl-L-glutaminyl-L-leucyl-(N6-(L-homoseryl))-L-lysine
-
enzyme binding structure, overview
-
L-seryl-L-arginyl-L-threonyl-L-methionyl-L-glutaminyl-L-threonyl-L-alanyl-L-arginyl-L-lysyl-L-seryl-L-threonylglycylglycyl-L-lysyl-L-alanyl-L-prolyl-L-arginyl-L-lysyl-L-glutaminyl-L-leucine
-
enzyme binding structure, overview
lithium 2-(((furan-2-ylmethyl)amino)methyl)isonicotinate
-
;
lithium 2-((benzylamino)methyl)isonicotinate
-
;
N'-(13,15-diimino-18,18-diphenyl-4,8,12,14,16-pentaazaoctadec-1-yl)-N-(2,2-diphenylethyl)imidodicarbonimidic diamide
-
1 mM, about 65% inhibition. Inhibition affects a reexpression of multiple, aberrantly silenced genes important in the develoment of colon cancer. Reexpression is concurrent with increased dimethylated histone 3 lysine 4 and acetyl-histone 3 lysine 4 marks
N'-(14,16-diimino-20,20-diphenyl-4,9,13,15,17-pentaazaicos-1-yl)-N-(3,3-diphenylpropyl)imidodicarbonimidic diamide
-
1 mM, about 70% inhibition. Inhibition affects a reexpression of multiple, aberrantly silenced genes important in the develoment of colon cancer. Reexpression is concurrent with increased dimethylated histone 3 lysine 4 and acetyl-histone 3 lysine 4 marks
N'-(17,19-diimino-23,23-diphenyl-4,12,16,18,20-pentaazatricos-1-yl)-N-(3,3-diphenylpropyl)imidodicarbonimidic diamide
-
1 mM, about 90% inhibition. Inhibition affects a reexpression of multiple, aberrantly silenced genes important in the develoment of colon cancer. Reexpression is concurrent with increased dimethylated histone 3 lysine 4 and acetyl-histone 3 lysine 4 marks
N,N'-diethyl-5,11,17,22,27,33-hexaazaoctatriacontane-1,38-diamine
-
-
N,N'-diethyl-5,11,17,23,28,33,39,45-octaazapentacontane-1,50-diamine
-
-
N-(hydroxyacetyl)-L-alanyl-L-arginyl-L-threonyl-L-methionyl-L-glutaminyl-L-threonyl-L-alanyl-L-arginyl-L-lysyl-L-seryl-L-threonylglycylglycyl-L-lysyl-L-alanyl-L-prolyl-L-arginyl-N6-(hydroxyacetyl)-L-lysyl-L-glutaminyl-L-leucine
-
-
N-(hydroxyacetyl)-L-alanyl-L-arginyl-L-threonyl-L-methionyl-L-glutaminyl-L-threonyl-L-alanyl-L-arginyl-L-lysyl-L-seryl-L-threonylglycylglycyl-N6-(hydroxyacetyl)-L-lysyl-L-alanyl-L-prolyl-L-arginyl-L-lysyl-L-glutaminyl-L-leucine
-
-
N-ethyl-N'-[[2-([[4-([[2-([[4-(ethylamino)butyl]amino]methyl)cyclopropyl]methyl]amino)butyl]amino]methyl)cyclopropyl]methyl]butane-1,4-diamine
-
-
N-methyl-N-propargylbenzylamine hydrochloride
-
i.e. pargyline
-
N-oxalylglycine
i.e. NOG, a non-reactive 2-oxoglutarate analogue
N2-L-alanyl-L-arginyl-L-threonyl-L-methionyl-L-glutaminyl-L-threonyl-L-alanyl-L-arginyl-L-lysyl-L-seryl-L-threonylglycylglycyl-L-lysyl-L-alanyl-L-prolyl-L-arginyl-N6-(2-hydroxyacetyl)-L-lysyl-L-glutaminyl-L-leucine
-
-
N2-L-alanyl-L-arginyl-L-threonyl-L-methionyl-L-glutaminyl-L-threonyl-L-alanyl-L-arginyl-L-lysyl-L-seryl-L-threonylglycylglycyl-N6-(2-hydroxyacetyl)-L-lysyl-L-alanyl-L-prolyl-L-arginyl-L-lysyl-L-glutaminyl-L-leucine
-
-
N2-L-seryl-L-arginyl-L-threonyl-L-methionyl-L-glutaminyl-L-threonyl-L-alanyl-L-arginyl-L-lysyl-L-seryl-L-threonylglycylglycyl-L-lysyl-L-alanyl-L-prolyl-L-arginyl-(N6-(L-seryl))-L-lysyl-L-glutaminyl-L-leucine
-
-
N2-L-seryl-L-arginyl-L-threonyl-L-methionyl-L-glutaminyl-L-threonyl-L-alanyl-L-arginyl-L-lysyl-L-seryl-L-threonylglycylglycyl-L-lysyl-L-alanyl-L-prolyl-L-arginyl-L-lysyl-L-glutaminyl-L-leucyl-(N6-(L-seryl))-L-lysine-amide
-
enzyme binding structure, overview
N2-L-seryl-L-arginyl-L-threonyl-L-methionyl-L-glutaminyl-L-threonyl-L-alanyl-L-arginyl-L-lysyl-L-seryl-L-threonylglycylglycyl-L-lysyl-L-alanyl-L-prolyl-L-arginyl-L-lysyl-L-glutaminyl-L-leucyl-L-alanyl-L-threonyl-(N6-(L-seryl))-L-lysine-amide
-
-
Ni2+
substitutes Fe2+ and inhibits the hydroxylation reaction
NURF-1
-
an H3K4me3-binding protein and member of the chromatin-remodeling complex NURF, is required for promoting aberrant wsp-1 transcription in rbr-2 mutants and its ablation restores wild-type expression of wsp-1 and axon guidance
-
Pargyline
peptide H31-21
-
21-mer H3-derived peptide
-
peptide H3K4M
-
the modified H3 peptide with substitution of Lys4 to Met [H3K4M] is known to be a potent competitive inhibitor of LSD1
-
pyrido[3,4-d]pyrimidin-4(3H)-one
-
;
trans-2-phenylcyclopropylamine
-
i.e. parnate or tranylcypromine, TCP
Tranylcypromine
additional information
-
ACTIVATING COMPOUND
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
ascorbate
-
required
HP1a
-
Suv(Var)3-9/KMT1 interacts with HP1 that binds [histone H3]-N6,N6-trimethyl-L-lysine9
-
N-oxalylglycine
required, essential for the demethylase activity in vivo
tetrahydrofolate
-
-
additional information
-
KM VALUE [mM]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
additional information
additional information
-
Michaelis-Menten kinetics of wild-type and mutant enzymes; Michaelis-Menten kinetics of wild-type and mutant enzymes
-
Ki VALUE [mM]
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
0.5
(2-hydroxyacetyl)-L-alanyl-L-arginyl-L-threonyl-L-methionyl-L-glutaminyl-L-threonyl-L-alanyl-L-arginyl-L-lysyl-L-seryl-L-threonylglycylglycyl-L-lysyl-L-alanyl-L-prolyl-L-arginyl-L-lysyl-L-glutaminyl-L-leucine
-
pH 7.5, 25C
0.17
(2-hydroxyacetyl)-L-arginyl-L-threonyl-L-methionyl-L-glutaminyl-L-threonyl-L-alanyl-L-arginyl-L-lysyl-L-seryl-L-threonylglycylglycyl-L-lysyl-L-alanyl-L-prolyl-L-arginyl-L-lysyl-L-glutaminyl-L-leucine
-
pH 7.5, 25C
0.00189
histone H3
-
pH 7.5, 25C
-
0.000098
L-alanyl-L-arginyl-L-threonyl-L-methionyl-L-glutaminyl-L-threonyl-L-alanyl-L-arginyl-L-lysyl-L-seryl-L-threonylglycylglycyl-L-lysyl-L-alanyl-L-prolyl-L-arginyl-L-lysyl-L-glutaminyl-L-leucine
-
pH 7.5, 25C
0.5
L-arginyl-L-threonyl-L-methionyl-L-glutaminyl-L-threonyl-L-alanyl-L-arginyl-L-lysyl-L-seryl-L-threonylglycylglycyl-L-lysyl-L-alanyl-L-prolyl-L-arginyl-L-lysyl-L-glutaminyl-L-leucine
-
pH 7.5, 25C
0.0063
L-homoseryseryl-L-arginyl-L-threonyl-L-methionyl-L-glutaminyl-L-threonyl-L-alanyl-L-arginyl-L-lysyl-L-seryl-L-threonylglycylglycyl-L-lysyl-L-alanyl-L-prolyl-L-arginyl-L-lysyl-L-glutaminyl-L-leucyl-(N6-(L-homoseryl))-L-lysine
-
pH 7.5, 25C
-
0.00003
L-seryl-L-arginyl-L-threonyl-L-methionyl-L-glutaminyl-L-threonyl-L-alanyl-L-arginyl-L-lysyl-L-seryl-L-threonylglycylglycyl-L-lysyl-L-alanyl-L-prolyl-L-arginyl-L-lysyl-L-glutaminyl-L-leucine
-
pH 7.5, 25C
0.5
N-(hydroxyacetyl)-L-alanyl-L-arginyl-L-threonyl-L-methionyl-L-glutaminyl-L-threonyl-L-alanyl-L-arginyl-L-lysyl-L-seryl-L-threonylglycylglycyl-L-lysyl-L-alanyl-L-prolyl-L-arginyl-N6-(hydroxyacetyl)-L-lysyl-L-glutaminyl-L-leucine
-
pH 7.5, 25C
0.5
N-(hydroxyacetyl)-L-alanyl-L-arginyl-L-threonyl-L-methionyl-L-glutaminyl-L-threonyl-L-alanyl-L-arginyl-L-lysyl-L-seryl-L-threonylglycylglycyl-N6-(hydroxyacetyl)-L-lysyl-L-alanyl-L-prolyl-L-arginyl-L-lysyl-L-glutaminyl-L-leucine
-
pH 7.5, 25C
0.0014
N2-L-alanyl-L-arginyl-L-threonyl-L-methionyl-L-glutaminyl-L-threonyl-L-alanyl-L-arginyl-L-lysyl-L-seryl-L-threonylglycylglycyl-L-lysyl-L-alanyl-L-prolyl-L-arginyl-N6-(2-hydroxyacetyl)-L-lysyl-L-glutaminyl-L-leucine
-
pH 7.5, 25C
0.0098
N2-L-alanyl-L-arginyl-L-threonyl-L-methionyl-L-glutaminyl-L-threonyl-L-alanyl-L-arginyl-L-lysyl-L-seryl-L-threonylglycylglycyl-N6-(2-hydroxyacetyl)-L-lysyl-L-alanyl-L-prolyl-L-arginyl-L-lysyl-L-glutaminyl-L-leucine
-
pH 7.5, 25C
0.00038
N2-L-seryl-L-arginyl-L-threonyl-L-methionyl-L-glutaminyl-L-threonyl-L-alanyl-L-arginyl-L-lysyl-L-seryl-L-threonylglycylglycyl-L-lysyl-L-alanyl-L-prolyl-L-arginyl-(N6-(L-seryl))-L-lysyl-L-glutaminyl-L-leucine
-
pH 7.5, 25C
0.00006
N2-L-seryl-L-arginyl-L-threonyl-L-methionyl-L-glutaminyl-L-threonyl-L-alanyl-L-arginyl-L-lysyl-L-seryl-L-threonylglycylglycyl-L-lysyl-L-alanyl-L-prolyl-L-arginyl-L-lysyl-L-glutaminyl-L-leucyl-(N6-(L-seryl))-L-lysine-amide
-
pH 7.5, 25C
0.00029
N2-L-seryl-L-arginyl-L-threonyl-L-methionyl-L-glutaminyl-L-threonyl-L-alanyl-L-arginyl-L-lysyl-L-seryl-L-threonylglycylglycyl-L-lysyl-L-alanyl-L-prolyl-L-arginyl-L-lysyl-L-glutaminyl-L-leucyl-L-alanyl-L-threonyl-(N6-(L-seryl))-L-lysine-amide
-
pH 7.5, 25C
0.0018
peptide H31-21
-
pH 7.5, 25C
-
additional information
additional information
-
kinetic analysis of full-length histone products against KDM1A
-
IC50 VALUE [mM]
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
0.000098
2-(((2-((2-(dimethylamino)ethyl)(ethyl)amino)-2-oxoethyl)amino)methyl)-N-ethylisonicotinamide
Homo sapiens
Q9BY66
pH and temperature not specified in the publication
0.00027
2-(((2-((2-(dimethylamino)ethyl)(ethyl)amino)-2-oxoethyl)amino)methyl)-N-methylisonicotinamide
Homo sapiens
Q9BY66
pH and temperature not specified in the publication
0.000019 - 0.000071
2-(((2-((2-(dimethylamino)ethyl)(ethyl)amino)-2-oxoethyl)amino)methyl)isonicotinamide
0.000007
2-(((2-((2-(dimethylamino)ethyl)(ethyl)amino)-2-oxoethyl)amino)methyl)isonicotinic acid
Homo sapiens
Q9BY66
pH and temperature not specified in the publication
0.00098
2-(piperazin-1-ylmethyl)isonicotinic acid
Homo sapiens
Q9BY66
pH and temperature not specified in the publication
0.000048
ethyl 2-(((2-((2-(dimethylamino)ethyl)(ethyl)amino)-2-oxoethyl)amino)methyl)isonicotinate
Homo sapiens
Q9BY66
pH and temperature not specified in the publication
0.00484
peptide H31-21
Homo sapiens
-
pH 7.5, 25C
-
SPECIFIC ACTIVITY [µmol/min/mg]
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
0.00029
-
recombinant purified isozyme JMJD2B, substrate histone H3K9
0.0005
-
recombinant purified isozyme JMJD2C, substrate histone H3K9
0.001
-
recombinant purified isozyme JMJD2A, substrate histone H3K9
additional information
-
specific isozyme activities with non-histone substrates, overview
pH OPTIMUM
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
7.2 - 7.5
-
assay at
7.9
-
assay at
8
-
assay at
TEMPERATURE OPTIMUM
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
25
-
assay at
SOURCE TISSUE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
SOURCE
-
of control and hyperglycemic mice
Manually annotated by BRENDA team
-
low KDM5B expression level
Manually annotated by BRENDA team
histone H3-K4 demethylase is restricted to the corpus luteum
Manually annotated by BRENDA team
-
-
Manually annotated by BRENDA team
-
low KDM5B expression level
Manually annotated by BRENDA team
-
high KDM5B expression level
Manually annotated by BRENDA team
-
low KDM5B expression level
Manually annotated by BRENDA team
-
low KDM5B expression level
Manually annotated by BRENDA team
-
LSD1 is strongly expressed in poorly differentiated neuroblastomas, real-time reverse transcription-PCR expression analysis
Manually annotated by BRENDA team
-
histone H3 lysine 4 demethylase JARID1B is up-regulated in prostate cancer. JARID1B associates with androgen receptor and regulates its transcriptional activity
Manually annotated by BRENDA team
-
lysine-specific demethylase 1 colocalizes with androgen receptor
Manually annotated by BRENDA team
-
lysine-specific demethylase 1 colocalizes with androgen receptor
Manually annotated by BRENDA team
-
the highest expression of LSD1 occurs in postmitotic retinal cells during the peak period of rod photoreceptor differentiation. LSD1 appears to be absent at the outer margin of the retina, enzyme distribution, overview
Manually annotated by BRENDA team
-
JMJ703 is expressed at relatively high levels in leaves of 7 d-after-germination in seedlings compared with all of the other tissues tested
Manually annotated by BRENDA team
-
HER2+SKBR3 cell, low KDM5B expression level
Manually annotated by BRENDA team
-
low KDM5B expression level
Manually annotated by BRENDA team
-
high KDM5B expression level
Manually annotated by BRENDA team
-
Beko cell, spontaneous T-cell lymphoma cell line derived from T-cell receptor beta knockout mice, only KDM5A and KDM5C are expressed
Manually annotated by BRENDA team
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specific expression of PLU-1
Manually annotated by BRENDA team
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high KDM5B expression level
Manually annotated by BRENDA team
additional information
LOCALIZATION
ORGANISM
UNIPROT
COMMENTARY hide
GeneOntology No.
LITERATURE
SOURCE
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LSD1 is present on chromatin in both the presence and the absence of estrogens
Manually annotated by BRENDA team
additional information
MOLECULAR WEIGHT
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
95059
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1 * 95059, LSD1 without N-terminal methionine, mass spectrometry
100000
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about, recombinant enzyme, gel filtration
192000
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SUBUNITS
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
monomer
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1 * 95059, LSD1 without N-terminal methionine, mass spectrometry
additional information
Crystallization/COMMENTARY
ORGANISM
UNIPROT
LITERATURE
crystallization of JMJD2A in complex with histone H3 peptides bearing different methylated forms of K9 and K36, cocrystallization of inactivated substrate with either N-oxalylglycine, a non-reactive 2-OG analog, or with Ni(II), which substitutes for Fe(II) and inhibits the hydroxylation reaction. Structures analysis, overview
in complex with inhibitor tranylcypromine, diffraction to 2.25 A. In the inhibitor-free structure, a water molecule forms a hydrogen bond with the flavin N(5) atom and Lys661. The LSD1-tranylcypromine complex is not completely composed of the five-membered adduct, but partially contains an intermediate
purified recombinant enzyme in complex with inhibitor KDOAM-25, sitting drop vapor diffusion method, mixing of 50 nl of 8.1 mg/ml protein in solution with 1 mM KDOAM-25 and 4 mM MnCl2, is mixed with ,precipitant solution consisting of 1.6 M Na/K phosphate, and 0.1 M HEPES, pH 7.5, and 20 nL of KDM5B seeds of crystals obtained from the same condition, 4C, X-ray diffraction structure determination and analysis at 2.0 A resolution, modeling
purified recombinant truncated enzyme LSD1 comprising residues 172-833 in complex with recombinant human CoREST residues 308-440, and peptide inhibitors 9, N2-L-seryl-L-arginyl-L-threonyl-L-methionyl-L-glutaminyl-L-threonyl-L-alanyl-L-arginyl-L-lysyl-L-seryl-L-threonylglycylglycyl-L-lysyl-L-alanyl-L-prolyl-L-arginyl-L-lysyl-L-glutaminyl-L-leucyl-(N6-(L-seryl))-L-lysine-amide, and L-homoseryseryl-L-arginyl-L-threonyl-L-methionyl-L-glutaminyl-L-threonyl-L-alanyl-L-arginyl-L-lysyl-L-seryl-L-threonylglycylglycyl-L-lysyl-L-alanyl-L-prolyl-L-arginyl-L-lysyl-L-glutaminyl-L-leucyl-(N6-(L-homoseryl))-L-lysine, by hanging drop vapor diffusion method, mixing of 0.001 ml of 9 mg/m protein solution with 0.001 ml of reservoir solution containing 100 mM N-(carbamoylmethyl)iminodiacetic acid, pH 5.5, and 1.18-1.28M potassium sodium tartrate tetrahydrate, 20C, crystals are soaked in a solution containing 100 mM N-(carbamoylmethyl) iminodiacetic acid buffer, pH 5.5, with 1.14 M potassium sodium tartrate tetrahydrate, 10% glycerol, and 2 mM LSD1 inhibitor peptide L-seryl-L-arginyl-L-threonyl-L-methionyl-L-glutaminyl-L-threonyl-L-alanyl-L-arginyl-L-lysyl-L-seryl-L-threonylglycylglycyl-L-lysyl-L-alanyl-L-prolyl-L-arginyl-L-lysyl-L-glutaminyl-L-leucine, 11 or 13 for 2 h, X-ray diffraction structure determination and analysis at 2.53-2.69 A resolution
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purified recombinant enzyme, free or in complex with N-oxalylglycine, X-ray diffraction structure determination and analysis at 2.35 A resolution
Purification/COMMENTARY
ORGANISM
UNIPROT
LITERATURE
recombinant FLAG:HA-tagged JmjN-JmjC-zinc finger region from Nicotiana tabacum leaf nuclei byy affinity chromatography
recombinant GST-tagged isozymes JMJD2A, JMJD2B, and JMJD2C from Escherichia coli strain BL21(DE3) by glutathione affinity chromatography
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recombinant His-SUMO-tagged enzyme from Escherichia coli strain BL21(DE3)C+ by nickel affinity chromatography, tag cleavage overnight by Ulp-1 protease, followed by anion exchange chromatography, gel filtration, and ultrafiltration; recombinant His-SUMO-tagged enzyme from Escherichia coli strain BL21(DE3)C+ by nickel affinity chromatography, tag cleavage overnight by Ulp-1 protease, followed by anion exchange chromatography, gel filtration, and ultrafiltration; recombinant His-SUMO-tagged enzyme from Escherichia coli strain BL21(DE3)C+ by nickel affinity chromatography, tag cleavage overnight by Ulp-1 protease, followed by anion exchange chromatography, gel filtration, and ultrafiltration. Deletion of DELTAAP has no effect on kinetics of KDM5C
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recombinant His-tagged N-terminal fragment of JARID1B from Sf9 insect cells by nickel affinity chromatography
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recombinant N-terminally FLAG-tagged KDM5A from HeLa cell nuclear extract by gel filtration and immunoaffinity chromatography, the enzyme copurifies with the SIN3B-HDAC complex, and with additional proteins including CHD4, MTA2, GATAD2A, ZMYND8A, ZNF592, and ZNF687. CHD4, MTA2, and GATAD2A are known components of the NuRD (nucleosome remodeling and deacetylase) complex
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recombinant N-terminally His-tagged enzyme by nickel affinity chromatography from Escherichia coli BL21(DE3), or by ammonium sulfate fractionation and anion exchange chromatography, recombinant N-terminally truncated GST-tagged LSD1 by glutathione affinity chromatography
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Cloned/COMMENTARY
ORGANISM
UNIPROT
LITERATURE
cDNA encoding for Myc-tagged JARID1B is transfected into HeLa cells, and the effect on histone lysine methylation is examined
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co-expression of FLAG-CMV-tagged hPc2 and the HA-tagged N-terminal fragment of JARDI1B in HEK-293T cells. Expression the His-tagged N-terminal fragment of JARID1B in Spodoptera frugiperda Sf9 cells using the baculovirus transfection system
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coexpression of HA-tagged SALL4 and FLAG-tagged LSD1 in HEK-293 cells, coexpression of LSD1 and SALL4 proteins in mouse bone marrow hematopoietic stem and progenitor cells
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expression in Escherichia coli
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expression of FLAG-tagged JMJD2A in Spodoptera frugiperda Sf9 cells
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expression of FLAG-tagged wild-type and H190A mutant Jmjd2c in mouse embryonic fibroblasts
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expression of His6-tagged LSD1 in Escherichia coli strain BL21(DE3)
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fragment consisting of residues 172-833, expression as glutathione S-transferase fusion protein in Escherichia coli
full-length Flag-tagged human PLU-1 is expressed in SF9 cells. PLU-1 is overexpressed in U2OS cells
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gene Aof1
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gene Aof2
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gene JHD2, recombinant expression of HA-tagged wild-type Jhd2 and H427A mutant in yeast cells
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gene JMJ15, quantitative RT-PCR enzyme expression analysis, pJMJ15-GUS and 35S-JMJ15-FLAG-HA constructs are transformed into Agrobacterium tumefaciens strain GV3101 and then transformed into plants using the floral dip method
gene JMJ703, functional overexpression of YFP-HA-tagged JMJ703 in Nicotiana tabacum cells
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gene JMJ703, functional transient overexpression of the FLAG:HA-tagged JmjN-JmjC-zinc finger region in Nicotiana tabacum leaf nuclei
gene JMJ706, DNA and amino acid sequence determination and analysis, phylogenetic analysis, expression as GST-fusion protein
gene KDM1A, quantitative real-time PCR enzyme expression analysis
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gene KDM1A, real-time PCR enzyme expression analysis
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gene Kdm1a, RT-PCR enzyme expression analysis
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gene KDM5A, cloned from a HeLa gene library, recombinant expression of N-terminally FLAG-tagged KDM5A in HeLa cells and HEK-293T cells, quantitative RT-PCR expression analysis
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gene KDM5A, recombinant coexpression of wild-type and mutant FLAG-tagged Piasy and HA-tagged Rbp2 from pcDNA3.1(+) HA expression vector and p33 Flag CMV7.1 expression vector, respectively, in HEK-293T cells
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gene KDM5A, recombinant expression of soluble His-SUMO-tagged enzyme in Escherichia coli strain BL21(DE3)C+; gene KDM5B, recombinant expression of soluble His-SUMO-tagged enzyme in Escherichia coli strain BL21(DE3)C+; gene KDM5C, recombinant expression ofsoluble His-SUMO-tagged enzyme in Escherichia coli strain BL21(DE3)C+
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gene Kdm5c, encoded on the X-chromosome, genotyping, quantitative real-time RT-PCR expression analysis
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gene MAL8P1.111, located on chromosome 8, DNA and amino acid sequence determination and analysis, detailed phylogenetic analysis, overview
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gene rbr2, generation of transgenic lines in which RBR-2::GFP expression is driven by the rbr-2 promoter showing that RBR-2 is ubiquitously expressed in embryos and larvae, gene rbr-2 interacts with many neuronal genes, overview
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gene SE14, map-based cloning of Se14, DNA and amino acid sequence determination and analysis, sequence comparisons, fine mapping of the Se14 locus on the short arm of chromosome 3, genetic interaction of the Se14 locus with other flowering time genes loci and gene expression analysis
JMJD2A-C genes, DNA and amino acid sequence determination and analysis, expression of the GST-tagged isozymes JMJD2A, JMJD2B, and JMJD2C in Escherichia coli strain BL21(DE3)
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LSD1 genome-wide mapping and expression analysis, LSD1 genomic regions overlap H3K4me2 regions, transcriptional corepressor LSD1 is enriched at the promoter regions of highly expressed genes in ES cells
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overexpression of FLAG-tagged CG15835 in S2 cells
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real-time reverse transcription-PCR expression analysis
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stable expression of Flag-tagged KDM5B in HEK-293 cells
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stable overexpression of N-terminally HA-tagged Fbxl10 in murine embryonic fibroblasts leading to an increase in cell and nuclear size and changes the transcriptome, but with no effect on proliferation, mitosis, and apoptosis or global histone marks, quantitative real-time PCR expression analysis
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EXPRESSION
ORGANISM
UNIPROT
LITERATURE
differentiation of neuroblastoma cells results in down-regulation of LSD1
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LSD1 expression in the brain is induced both region and cell specifically after ischemic/perfusion
ENGINEERING
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
D328A
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site-directed mutagenesis, a loss-of-function mutations in the PHD1 finger domain
H499A/E501A
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site-directed mutagenesis, inactive mutant
L326W
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site-directed mutagenesis, a loss-of-function mutations in the PHD1 finger domain
S288A
the mutant displays enhanced specificity for H3K9me2 and H3K36me2 without altering activity toward trimethyllysines, consistent with the H3K9me2/3 specificity of JMJD2D which possesses an alanine, Ala29, in this position. Kinetic analysis of S288A mutant shows a 12fold increase in H3K9me2 specificity versus the native enzyme, whereas the converse A291S mutant in JMJD2D reduces H3K9me2 specificity approximately fivefold
W1502A
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site-directed mutagenesis, a loss-of-function mutations in the PHD3 finger domain
H190A
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inactive mutant
H483A
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inactive KDM5A mutant
H483G/E485Q
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site-directed mutagenesis
K1096R
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the mutant Dnmt1 shows highly reduced Dnmt1 methylation activity compared to the wild-type enzyme, and is more stable than wild-type Dnmt1 when expressed in Dnmt1-/- embryonic stem cells
K152A
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site-directed mutagenesis
K152E
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site-directed mutagenesis
E396A
site directed mutagenesis of a Fe2+ binding active site residue, inactive mutant, the mutation impairs the H3K4 demethylase activity of JMJ703 in tobacco cells
G376A
site directed mutagenesis, inactive mutant, the mutation impairs the H3K4 demethylase activity of JMJ703 in tobacco cells, the mutation impairs the H3K4 demethylase activity of JMJ703 in tobacco cells
H394A
site directed mutagenesis of a Fe2+ binding active site residue, inactive mutant
H482A
site directed mutagenesis of a Fe2+ binding active site residue, inactive mutant
K412A
site directed mutagenesis, the mutation abolishes the demethylation activity of H3K4 in all three methylation states
N496A
site directed mutagenesis, the mutant retains a residual activity to demethylate H3K4me2/3, the mutation impairs the H3K4 demethylase activity of JMJ703 in tobacco cells
Y321A
site directed mutagenesis decreases H3K4me1 demethylase activity but does not affect H3K4me2 and H3K4me3 demethylase activity
Y383A
site directed mutagenesis, the mutant retains a residual activity to demethylate H3K4me2, the mutation impairs the H3K4 demethylase activity of JMJ703 in tobacco cells
H427A
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catalytically inactive mutant
additional information