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Information on EC 1.14.11.65 - [histone H3]-dimethyl-L-lysine9 demethylase
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1.14.11.65 [histone H3]-dimethyl-L-lysine9 demethylaseIUBMB Comments
Requires iron(II). This entry describes a group of enzymes that demethylate N-methylated Lys-9 residues in the tail of the histone protein H3 (H3K9). This lysine residue can exist in three methylation states (mono-, di- and trimethylated), but this group of enzymes only act on the the di- and mono-methylated forms. The enzymes are dioxygenases and act by hydroxylating the methyl group, forming an unstable hemiaminal that leaves as formaldehyde. cf. EC 1.14.11.66, [histone H3]-trimethyl-L-lysine9 demethylase.
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Word Map
- 1.14.11.65
- irradiation
-
cutaneous
- dermal
-
stratum
-
permeation
- corneum
-
transdermal
-
uvb-induced
- keratinocytes
- collagen
- carcinogenesis
- follicle
-
percutaneous
- notch
- erythema
- guinea
-
photoaging
-
wrinkle
- hyperplasia
-
solar
-
transepidermal
-
photocarcinogenesis
- flap
-
irritation
-
iontophoresis
- alopecia
- scalp
- dermatitis
-
photoprotective
-
uvb-irradiated
-
photodamage
- propylene
-
sebaceous
-
full-thickness
-
cream
-
tape
-
sunscreen
- sunburn
- demethylases
- dorsum
- nevus
-
ultraviolet-induced
-
cyclobutane
-
ointment
- 8-methoxypsoralen
-
bald
- tranylcypromine
- medicine
-
eyebrow
- drug development
-
sencar
-
intracutaneous
The enzyme appears in viruses and cellular organisms
Reaction Schemes
Synonyms
AOF2, AtJMJ17, BHC110, G9A/KMT1C, GLP/KMT1D, H3K4me2 demethylase, H3K9 demethylase, H3K9 histone demethylase, H3K9 Jumonji demethylase, H3K9 mono- and di-demethylase, 
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SYNONYM 
ORGANISM
UNIPROT
COMMENTARY 
LITERATURE
BHC110
H3K9 demethylase
histone demethylase
histone H3K9 demethylase
IBM1
JHDM2A
JMJ25
jmjC histone demethylase
JMJD1A
KDM1A
Kdm3a
Kdm3b
LSD1
lysine-specific demethylase 1
lysine-specific histone demethylase 1
PHF8
SWIRM1
Swm1
Swm1/2 complex
additional information
LSD1
-
lysine-specific demethylase 1
-
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REACTION
REACTION DIAGRAM
COMMENTARY
ORGANISM
UNIPROT
LITERATURE
a [histone H3]-N6,N6-dimethyl-L-lysine9 + 2 2-oxoglutarate + 2 O2 = a [histone H3]-L-lysine9 + 2 succinate + 2 formaldehyde + 2 CO2
overall reaction
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-
-
a [histone H3]-N6,N6-dimethyl-L-lysine9 + 2-oxoglutarate + O2 = a [histone H3]-N6-methyl-L-lysine9 + succinate + formaldehyde + CO2
(1a)
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-
-
a [histone H3]-N6-methyl-L-lysine9 + 2-oxoglutarate + O2 = a [histone H3]-L-lysine9 + succinate + formaldehyde + CO2
(1b)
-
-
-
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SYSTEMATIC NAME
IUBMB Comments
[histone H3]-N6,N6-dimethyl-L-lysine9,2-oxoglutarate:oxygen oxidoreductase
Requires iron(II). This entry describes a group of enzymes that demethylate N-methylated Lys-9 residues in the tail of the histone protein H3 (H3K9). This lysine residue can exist in three methylation states (mono-, di- and trimethylated), but this group of enzymes only act on the the di- and mono-methylated forms. The enzymes are dioxygenases and act by hydroxylating the methyl group, forming an unstable hemiaminal that leaves as formaldehyde. cf. EC 1.14.11.66, [histone H3]-trimethyl-L-lysine9 demethylase.
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SUBSTRATE
PRODUCT
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate)
(Substrate)
LITERATURE
(Substrate)
(Substrate)
COMMENTARY
(Product)
(Product)
LITERATURE
(Product)
(Product)
Reversibility
r=reversible
ir=irreversible
?=not specified
r=reversible
ir=irreversible
?=not specified
a [histone H3]-N6,N6-dimethyl-L-lysine9 + 2 2-oxoglutarate + 2 O2
a [histone H3]-L-lysine9 + 2 succinate + 2 formaldehyde + 2 CO2
a [histone H3]-N6,N6-dimethyl-L-lysine9 + 2-oxoglutarate + O2
a [histone H3]-N6-methyl-L-lysine9 + succinate + formaldehyde + CO2
a [histone H3]-N6-methyl-L-lysine9 + 2-oxoglutarate + O2
a [histone H3]-L-lysine9 + succinate + formaldehyde + CO2
histone H3 N6,N6,N6-trimethyl-L-lysine9 + 2-oxoglutarate + O2
histone H3 N6,N6-dimethyl-L-lysine9 + succinate + formaldehyde + CO2
histone H3 N6,N6-dimethyl-L-lysine9 + 2-oxoglutarate + O2
histone H3 N6-methyl-L-lysine9 + succinate + formaldehyde + CO2
histone H3 N6-methyl-L-lysine9 + 2-oxoglutarate + O2
histone H3 L-lysine9 + succinate + formaldehyde + CO2
histone H4 N6-methyl-L-lysine20 + 2-oxoglutarate + O2
histone H4 L-lysine20 + succinate + formaldehyde + CO2
-
-
-
?
protein 6-N,6-N-dimethyl-L-lysine + 2-oxoglutarate + O2
protein 6-N-methyl-L-lysine + succinate + formaldehyde + CO2
-
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
-
LSD1 relieves repressive histone marks by demethylation of histone H3 at lysine 9, thereby leading to derepression of androgen receptor target genes
-
-
?
[histone H3]-N6,N6,N6-trimethyl-L-lysine4 + 2-oxoglutarate + O2
[histone H3]-L-lysine4 + succinate + formaldehyde + CO2
-
-
-
-
?
[histone H3]-N6,N6-dimethyl-L-lysine 4 + 2-oxoglutarate + O2
[histone H3]-N6-methyl-L-lysine 4 + succinate + formaldehyde + CO2
-
-
-
?
[histone H3]-N6,N6-dimethyl-L-lysine 9 + 2-oxoglutarate + O2
[histone H3]-N6-methyl-L-lysine 9 + succinate + formaldehyde + CO2
[histone H3]-N6,N6-dimethyl-L-lysine27 + 2-oxoglutarate + O2
[histone H3]-N6-methyl-L-lysine27 + succinate + formaldehyde + CO2
-
-
-
?
[histone H3]-N6,N6-dimethyl-L-lysine4 + 2-oxoglutarate + O2
[histone H3]-L-lysine4 + succinate + formaldehyde + CO2
[histone H3]-N6,N6-dimethyl-L-lysine9 + 2 2-oxoglutarate + 2 O2
[histone H3]-L-lysine9 + 2 succinate + 2 formaldehyde + 2 CO2
[histone H3]-N6,N6-dimethyl-L-lysine9 + 2-oxoglutarate + O2
[histone H3]-N6-methyl-L-lysine9 + succinate + formaldehyde + CO2
[histone H3]-N6-methyl-L-lysine 4 + 2-oxoglutarate + O2
[histone H3]-L-lysine 4 + succinate + formaldehyde + CO2
-
-
-
?
[histone H3]-N6-methyl-L-lysine 9 + 2-oxoglutarate + O2
[histone H3]-L-lysine 9 + succinate + formaldehyde + CO2
[histone H3]-N6-methyl-L-lysine9 + 2-oxoglutarate + O2
[histone H3]-L-lysine9 + succinate + formaldehyde + CO2
[histone H4]-N6-methyl-L-lysine 20 + 2-oxoglutarate + O2
[histone H4]-L-lysine 20 + succinate + formaldehyde + CO2
a [histone H3]-N6,N6-dimethyl-L-lysine9 + 2 2-oxoglutarate + 2 O2
a [histone H3]-L-lysine9 + 2 succinate + 2 formaldehyde + 2 CO2
-
-
-
?
a [histone H3]-N6,N6-dimethyl-L-lysine9 + 2 2-oxoglutarate + 2 O2
a [histone H3]-L-lysine9 + 2 succinate + 2 formaldehyde + 2 CO2
-
-
-
?
a [histone H3]-N6,N6-dimethyl-L-lysine9 + 2 2-oxoglutarate + 2 O2
a [histone H3]-L-lysine9 + 2 succinate + 2 formaldehyde + 2 CO2
-
overall reaction
-
-
?
a [histone H3]-N6,N6-dimethyl-L-lysine9 + 2-oxoglutarate + O2
a [histone H3]-N6-methyl-L-lysine9 + succinate + formaldehyde + CO2
-
-
-
?
a [histone H3]-N6,N6-dimethyl-L-lysine9 + 2-oxoglutarate + O2
a [histone H3]-N6-methyl-L-lysine9 + succinate + formaldehyde + CO2
-
-
-
?
a [histone H3]-N6,N6-dimethyl-L-lysine9 + 2-oxoglutarate + O2
a [histone H3]-N6-methyl-L-lysine9 + succinate + formaldehyde + CO2
-
-
-
?
a [histone H3]-N6,N6-dimethyl-L-lysine9 + 2-oxoglutarate + O2
a [histone H3]-N6-methyl-L-lysine9 + succinate + formaldehyde + CO2
-
-
-
?
a [histone H3]-N6,N6-dimethyl-L-lysine9 + 2-oxoglutarate + O2
a [histone H3]-N6-methyl-L-lysine9 + succinate + formaldehyde + CO2
-
-
-
-
?
a [histone H3]-N6-methyl-L-lysine9 + 2-oxoglutarate + O2
a [histone H3]-L-lysine9 + succinate + formaldehyde + CO2
-
-
-
?
a [histone H3]-N6-methyl-L-lysine9 + 2-oxoglutarate + O2
a [histone H3]-L-lysine9 + succinate + formaldehyde + CO2
-
-
-
?
a [histone H3]-N6-methyl-L-lysine9 + 2-oxoglutarate + O2
a [histone H3]-L-lysine9 + succinate + formaldehyde + CO2
-
-
-
?
a [histone H3]-N6-methyl-L-lysine9 + 2-oxoglutarate + O2
a [histone H3]-L-lysine9 + succinate + formaldehyde + CO2
-
-
-
?
a [histone H3]-N6-methyl-L-lysine9 + 2-oxoglutarate + O2
a [histone H3]-L-lysine9 + succinate + formaldehyde + CO2
-
-
-
-
?
histone H3 N6,N6,N6-trimethyl-L-lysine9 + 2-oxoglutarate + O2
histone H3 N6,N6-dimethyl-L-lysine9 + succinate + formaldehyde + CO2
-
-
-
?
histone H3 N6,N6,N6-trimethyl-L-lysine9 + 2-oxoglutarate + O2
histone H3 N6,N6-dimethyl-L-lysine9 + succinate + formaldehyde + CO2
calf thymus histone substrate
-
-
?
histone H3 N6,N6,N6-trimethyl-L-lysine9 + 2-oxoglutarate + O2
histone H3 N6,N6-dimethyl-L-lysine9 + succinate + formaldehyde + CO2
-
-
-
?
histone H3 N6,N6,N6-trimethyl-L-lysine9 + 2-oxoglutarate + O2
histone H3 N6,N6-dimethyl-L-lysine9 + succinate + formaldehyde + CO2
JMJD1A binds to the MALAT1 gene promoter and demethylates histone H3K9 at the MALAT1 gene promoter
-
-
?
histone H3 N6,N6-dimethyl-L-lysine9 + 2-oxoglutarate + O2
histone H3 N6-methyl-L-lysine9 + succinate + formaldehyde + CO2
-
-
-
?
histone H3 N6,N6-dimethyl-L-lysine9 + 2-oxoglutarate + O2
histone H3 N6-methyl-L-lysine9 + succinate + formaldehyde + CO2
calf thymus histone substrate
-
-
?
histone H3 N6,N6-dimethyl-L-lysine9 + 2-oxoglutarate + O2
histone H3 N6-methyl-L-lysine9 + succinate + formaldehyde + CO2
-
-
-
?
histone H3 N6,N6-dimethyl-L-lysine9 + 2-oxoglutarate + O2
histone H3 N6-methyl-L-lysine9 + succinate + formaldehyde + CO2
-
-
-
?
histone H3 N6,N6-dimethyl-L-lysine9 + 2-oxoglutarate + O2
histone H3 N6-methyl-L-lysine9 + succinate + formaldehyde + CO2
-
-
-
?
histone H3 N6,N6-dimethyl-L-lysine9 + 2-oxoglutarate + O2
histone H3 N6-methyl-L-lysine9 + succinate + formaldehyde + CO2
-
-
-
?
histone H3 N6,N6-dimethyl-L-lysine9 + 2-oxoglutarate + O2
histone H3 N6-methyl-L-lysine9 + succinate + formaldehyde + CO2
-
-
-
?
histone H3 N6,N6-dimethyl-L-lysine9 + 2-oxoglutarate + O2
histone H3 N6-methyl-L-lysine9 + succinate + formaldehyde + CO2
-
-
-
?
histone H3 N6,N6-dimethyl-L-lysine9 + 2-oxoglutarate + O2
histone H3 N6-methyl-L-lysine9 + succinate + formaldehyde + CO2
-
-
-
?
histone H3 N6,N6-dimethyl-L-lysine9 + 2-oxoglutarate + O2
histone H3 N6-methyl-L-lysine9 + succinate + formaldehyde + CO2
-
PHF8 is able to demethylate H3K9me2 and H3K9me1
-
-
?
histone H3 N6,N6-dimethyl-L-lysine9 + 2-oxoglutarate + O2
histone H3 N6-methyl-L-lysine9 + succinate + formaldehyde + CO2
-
PHF8 is able to demethylate H3K9me2 and H3K9me1. The PHD domain adjacent to the catalytic domain in PHF8 may recognize methyl H3K9 and contribute to its demethylation
-
-
?
histone H3 N6,N6-dimethyl-L-lysine9 + 2-oxoglutarate + O2
histone H3 N6-methyl-L-lysine9 + succinate + formaldehyde + CO2
-
-
-
?
histone H3 N6-methyl-L-lysine9 + 2-oxoglutarate + O2
histone H3 L-lysine9 + succinate + formaldehyde + CO2
-
-
-
-
?
histone H3 N6-methyl-L-lysine9 + 2-oxoglutarate + O2
histone H3 L-lysine9 + succinate + formaldehyde + CO2
-
-
-
?
histone H3 N6-methyl-L-lysine9 + 2-oxoglutarate + O2
histone H3 L-lysine9 + succinate + formaldehyde + CO2
-
-
-
?
histone H3 N6-methyl-L-lysine9 + 2-oxoglutarate + O2
histone H3 L-lysine9 + succinate + formaldehyde + CO2
-
-
-
?
histone H3 N6-methyl-L-lysine9 + 2-oxoglutarate + O2
histone H3 L-lysine9 + succinate + formaldehyde + CO2
-
-
-
?
histone H3 N6-methyl-L-lysine9 + 2-oxoglutarate + O2
histone H3 L-lysine9 + succinate + formaldehyde + CO2
-
-
-
?
[histone H3]-N6,N6-dimethyl-L-lysine 9 + 2-oxoglutarate + O2
[histone H3]-N6-methyl-L-lysine 9 + succinate + formaldehyde + CO2
-
-
-
?
[histone H3]-N6,N6-dimethyl-L-lysine 9 + 2-oxoglutarate + O2
[histone H3]-N6-methyl-L-lysine 9 + succinate + formaldehyde + CO2
-
-
-
?
[histone H3]-N6,N6-dimethyl-L-lysine 9 + 2-oxoglutarate + O2
[histone H3]-N6-methyl-L-lysine 9 + succinate + formaldehyde + CO2
-
-
-
?
[histone H3]-N6,N6-dimethyl-L-lysine 9 + 2-oxoglutarate + O2
[histone H3]-N6-methyl-L-lysine 9 + succinate + formaldehyde + CO2
-
-
-
?
[histone H3]-N6,N6-dimethyl-L-lysine 9 + 2-oxoglutarate + O2
[histone H3]-N6-methyl-L-lysine 9 + succinate + formaldehyde + CO2
-
-
-
?
[histone H3]-N6,N6-dimethyl-L-lysine 9 + 2-oxoglutarate + O2
[histone H3]-N6-methyl-L-lysine 9 + succinate + formaldehyde + CO2
-
-
-
?
[histone H3]-N6,N6-dimethyl-L-lysine 9 + 2-oxoglutarate + O2
[histone H3]-N6-methyl-L-lysine 9 + succinate + formaldehyde + CO2
-
-
-
?
[histone H3]-N6,N6-dimethyl-L-lysine 9 + 2-oxoglutarate + O2
[histone H3]-N6-methyl-L-lysine 9 + succinate + formaldehyde + CO2
-
-
-
?
[histone H3]-N6,N6-dimethyl-L-lysine 9 + 2-oxoglutarate + O2
[histone H3]-N6-methyl-L-lysine 9 + succinate + formaldehyde + CO2
-
-
-
?
[histone H3]-N6,N6-dimethyl-L-lysine 9 + 2-oxoglutarate + O2
[histone H3]-N6-methyl-L-lysine 9 + succinate + formaldehyde + CO2
substrates are calf thymus bulk histones, chicken poly-nucleosomes, calf thymus histone H3, or recombinant Xenopus laevis H3
-
-
?
[histone H3]-N6,N6-dimethyl-L-lysine 9 + 2-oxoglutarate + O2
[histone H3]-N6-methyl-L-lysine 9 + succinate + formaldehyde + CO2
-
-
-
?
[histone H3]-N6,N6-dimethyl-L-lysine 9 + 2-oxoglutarate + O2
[histone H3]-N6-methyl-L-lysine 9 + succinate + formaldehyde + CO2
substrates are calf thymus bulk histones, chicken poly-nucleosomes, calf thymus histone H3, or recombinant Xenopus laevis H3
-
-
?
[histone H3]-N6,N6-dimethyl-L-lysine 9 + 2-oxoglutarate + O2
[histone H3]-N6-methyl-L-lysine 9 + succinate + formaldehyde + CO2
-
-
-
?
[histone H3]-N6,N6-dimethyl-L-lysine 9 + 2-oxoglutarate + O2
[histone H3]-N6-methyl-L-lysine 9 + succinate + formaldehyde + CO2
substrates are calf thymus bulk histones, chicken poly-nucleosomes, calf thymus histone H3, or recombinant Xenopus laevis H3
-
-
?
[histone H3]-N6,N6-dimethyl-L-lysine4 + 2-oxoglutarate + O2
[histone H3]-L-lysine4 + succinate + formaldehyde + CO2
-
-
-
-
?
[histone H3]-N6,N6-dimethyl-L-lysine4 + 2-oxoglutarate + O2
[histone H3]-L-lysine4 + succinate + formaldehyde + CO2
-
LSD1 is associated with protein BHC80. Upon demethylation of H3K4me2 to H3K4me0 by LSD1/KDM1, BHC80 binds the demethylation product H3K4me0 to maintain LSD1/KDM1 at target loci and to prevent re-methylation of H3K4
-
-
?
[histone H3]-N6,N6-dimethyl-L-lysine9 + 2 2-oxoglutarate + 2 O2
[histone H3]-L-lysine9 + 2 succinate + 2 formaldehyde + 2 CO2
overall reaction
-
-
?
[histone H3]-N6,N6-dimethyl-L-lysine9 + 2 2-oxoglutarate + 2 O2
[histone H3]-L-lysine9 + 2 succinate + 2 formaldehyde + 2 CO2
-
-
-
-
?
[histone H3]-N6,N6-dimethyl-L-lysine9 + 2 2-oxoglutarate + 2 O2
[histone H3]-L-lysine9 + 2 succinate + 2 formaldehyde + 2 CO2
-
the lysine methylase complexes recognize its own reaction products. The H3K9me2 methylases G9A/KMT1C and GLP/KMT1D, can also bind to their reaction product H3K9me2 via their ankyrin repeat domains
-
-
?
[histone H3]-N6,N6-dimethyl-L-lysine9 + 2 2-oxoglutarate + 2 O2
[histone H3]-L-lysine9 + 2 succinate + 2 formaldehyde + 2 CO2
-
-
-
-
?
[histone H3]-N6,N6-dimethyl-L-lysine9 + 2 2-oxoglutarate + 2 O2
[histone H3]-L-lysine9 + 2 succinate + 2 formaldehyde + 2 CO2
-
-
-
?
[histone H3]-N6,N6-dimethyl-L-lysine9 + 2 2-oxoglutarate + 2 O2
[histone H3]-L-lysine9 + 2 succinate + 2 formaldehyde + 2 CO2
overall reaction
-
-
?
[histone H3]-N6,N6-dimethyl-L-lysine9 + 2 2-oxoglutarate + 2 O2
[histone H3]-L-lysine9 + 2 succinate + 2 formaldehyde + 2 CO2
overall reaction
-
-
?
[histone H3]-N6,N6-dimethyl-L-lysine9 + 2 2-oxoglutarate + 2 O2
[histone H3]-L-lysine9 + 2 succinate + 2 formaldehyde + 2 CO2
overall reaction
-
-
?
[histone H3]-N6,N6-dimethyl-L-lysine9 + 2 2-oxoglutarate + 2 O2
[histone H3]-L-lysine9 + 2 succinate + 2 formaldehyde + 2 CO2
-
-
-
-
?
[histone H3]-N6,N6-dimethyl-L-lysine9 + 2 2-oxoglutarate + 2 O2
[histone H3]-L-lysine9 + 2 succinate + 2 formaldehyde + 2 CO2
-
Jmjd2c is recruited to the P2 promoter region of Mdm2 gene resulting in demethylation of histone H3 lysine 9, as typically found in actively transcribed genes
-
-
?
[histone H3]-N6,N6-dimethyl-L-lysine9 + 2 2-oxoglutarate + 2 O2
[histone H3]-L-lysine9 + 2 succinate + 2 formaldehyde + 2 CO2
-
-
-
-
?
[histone H3]-N6,N6-dimethyl-L-lysine9 + 2 2-oxoglutarate + 2 O2
[histone H3]-L-lysine9 + 2 succinate + 2 formaldehyde + 2 CO2
-
propagation of the silencing mark, H3K9me3, at the centromeric and Mating type regions requires the RNAi machinery and DNA recognition factors
-
-
?
[histone H3]-N6,N6-dimethyl-L-lysine9 + 2-oxoglutarate + O2
[histone H3]-N6-methyl-L-lysine9 + succinate + formaldehyde + CO2
-
-
-
?
[histone H3]-N6,N6-dimethyl-L-lysine9 + 2-oxoglutarate + O2
[histone H3]-N6-methyl-L-lysine9 + succinate + formaldehyde + CO2
-
-
-
?
[histone H3]-N6,N6-dimethyl-L-lysine9 + 2-oxoglutarate + O2
[histone H3]-N6-methyl-L-lysine9 + succinate + formaldehyde + CO2
-
-
-
?
[histone H3]-N6,N6-dimethyl-L-lysine9 + 2-oxoglutarate + O2
[histone H3]-N6-methyl-L-lysine9 + succinate + formaldehyde + CO2
-
-
-
?
[histone H3]-N6,N6-dimethyl-L-lysine9 + 2-oxoglutarate + O2
[histone H3]-N6-methyl-L-lysine9 + succinate + formaldehyde + CO2
-
-
-
?
[histone H3]-N6-methyl-L-lysine 9 + 2-oxoglutarate + O2
[histone H3]-L-lysine 9 + succinate + formaldehyde + CO2
-
-
-
?
[histone H3]-N6-methyl-L-lysine 9 + 2-oxoglutarate + O2
[histone H3]-L-lysine 9 + succinate + formaldehyde + CO2
-
-
-
?
[histone H3]-N6-methyl-L-lysine 9 + 2-oxoglutarate + O2
[histone H3]-L-lysine 9 + succinate + formaldehyde + CO2
-
-
-
?
[histone H3]-N6-methyl-L-lysine 9 + 2-oxoglutarate + O2
[histone H3]-L-lysine 9 + succinate + formaldehyde + CO2
-
-
-
?
[histone H3]-N6-methyl-L-lysine 9 + 2-oxoglutarate + O2
[histone H3]-L-lysine 9 + succinate + formaldehyde + CO2
-
-
-
?
[histone H3]-N6-methyl-L-lysine 9 + 2-oxoglutarate + O2
[histone H3]-L-lysine 9 + succinate + formaldehyde + CO2
-
-
-
?
[histone H3]-N6-methyl-L-lysine 9 + 2-oxoglutarate + O2
[histone H3]-L-lysine 9 + succinate + formaldehyde + CO2
-
-
-
?
[histone H3]-N6-methyl-L-lysine 9 + 2-oxoglutarate + O2
[histone H3]-L-lysine 9 + succinate + formaldehyde + CO2
-
-
-
?
[histone H3]-N6-methyl-L-lysine 9 + 2-oxoglutarate + O2
[histone H3]-L-lysine 9 + succinate + formaldehyde + CO2
-
-
-
?
[histone H3]-N6-methyl-L-lysine 9 + 2-oxoglutarate + O2
[histone H3]-L-lysine 9 + succinate + formaldehyde + CO2
substrates are calf thymus bulk histones, chicken poly-nucleosomes, calf thymus histone H3, or recombinant Xenopus laevis H3
-
-
?
[histone H3]-N6-methyl-L-lysine 9 + 2-oxoglutarate + O2
[histone H3]-L-lysine 9 + succinate + formaldehyde + CO2
-
-
-
?
[histone H3]-N6-methyl-L-lysine 9 + 2-oxoglutarate + O2
[histone H3]-L-lysine 9 + succinate + formaldehyde + CO2
substrates are calf thymus bulk histones, chicken poly-nucleosomes, calf thymus histone H3, or recombinant Xenopus laevis H3
-
-
?
[histone H3]-N6-methyl-L-lysine 9 + 2-oxoglutarate + O2
[histone H3]-L-lysine 9 + succinate + formaldehyde + CO2
-
-
-
?
[histone H3]-N6-methyl-L-lysine 9 + 2-oxoglutarate + O2
[histone H3]-L-lysine 9 + succinate + formaldehyde + CO2
substrates are calf thymus bulk histones, chicken poly-nucleosomes, calf thymus histone H3, or recombinant Xenopus laevis H3
-
-
?
[histone H3]-N6-methyl-L-lysine9 + 2-oxoglutarate + O2
[histone H3]-L-lysine9 + succinate + formaldehyde + CO2
-
-
-
?
[histone H3]-N6-methyl-L-lysine9 + 2-oxoglutarate + O2
[histone H3]-L-lysine9 + succinate + formaldehyde + CO2
-
-
-
-
?
[histone H3]-N6-methyl-L-lysine9 + 2-oxoglutarate + O2
[histone H3]-L-lysine9 + succinate + formaldehyde + CO2
-
-
-
?
[histone H3]-N6-methyl-L-lysine9 + 2-oxoglutarate + O2
[histone H3]-L-lysine9 + succinate + formaldehyde + CO2
-
-
-
?
[histone H3]-N6-methyl-L-lysine9 + 2-oxoglutarate + O2
[histone H3]-L-lysine9 + succinate + formaldehyde + CO2
-
-
-
?
[histone H4]-N6-methyl-L-lysine 20 + 2-oxoglutarate + O2
[histone H4]-L-lysine 20 + succinate + formaldehyde + CO2
-
-
-
?
[histone H4]-N6-methyl-L-lysine 20 + 2-oxoglutarate + O2
[histone H4]-L-lysine 20 + succinate + formaldehyde + CO2
-
-
-
?
additional information
?
-
JMJ27 displays H3K9me1/2 demethylase activity both in vitro and in vivo
-
-
?
additional information
?
-
enzyme substrate specificity for different lysine residues on different histones, JMJ27 is specific for lysine 9 residues of histone H3, overview
-
-
?
additional information
?
-
enzyme acts additionally as mono-methyl histone H4 lysine 20 demethylase
-
-
?
additional information
?
-
-
dynamic nature of histone methylation regulation on four of the main lysine sites of methylation on histone H3 and H4 tails, i.e. H3K4, H3K9, H3K27 and H3K36, overview. Methylation of non-histone proteins may be a general means to regulate epigenetic information
-
-
?
additional information
?
-
-
dynamic nature of histone methylation regulation on four of the main lysine sites of methylation on histone H3 and H4 tails, i.e. H3K4, H3K9, H3K27 and H3K36, overview. Methylation of non-histone proteins may be a general means to regulate epigenetic information. Upon stimulation, the bivalent domains segregate into either H3K4me3- or H3K27me3 marked genes for activation and repression, respectively
-
-
?
additional information
?
-
-
LSD1 is also responsible for demethylation of H3K4me2
-
-
?
additional information
?
-
LSD1 specificity and mechanism of action are complex-dependent
-
-
?
additional information
?
-
-
the PHD domain of human PHF8 interacts with the catalytic core in a manner similar to ceKIAA1718 of Caenorhabditis elegans, and the C-terminal coiled-coil region interacts with the catalytic core. JHDM1a binds methyl H3K36, while PHF8 does not
-
-
?
additional information
?
-
-
identification of multiple enzyme target genes, many of which play important roles in epidermal development, neural function, and transcriptional regulation, consistent with the predicted biological functions of enzyme hairless, HR, genomic target genes of HR, overview
-
-
?
additional information
?
-
identification of multiple enzyme target genes, many of which play important roles in epidermal development, neural function, and transcriptional regulation, consistent with the predicted biological functions of enzyme hairless, HR, genomic target genes of HR, overview
-
-
?
additional information
?
-
KDM1A catalyzes the oxidative demethylation of histone H3K4me1/2 and H3K9me1/2 as well as non-histone substrates
-
-
?
additional information
?
-
-
KDM3A is a histone demethylase that specifically demethylates mono-methylated (me1) and di-methylated (me2) histone H3 lysine 9 (H3K9)
-
-
?
additional information
?
-
KDM3A is a histone demethylase that specifically demethylates mono-methylated (me1) and di-methylated (me2) histone H3 lysine 9 (H3K9)
-
-
?
additional information
?
-
PHF8 demethylates H3K9me1, and if overexpressed also of H3K9me2 and H4K20me1 in endothelial cells, whereas H3K27me1/2 and H3K4me3, the latter being thought to act as anchor for PHF8, are not affected
-
-
?
additional information
?
-
-
enzyme hairless can demethylate monomethylated or dimethylated histone H3 lysine 9 (H3K9me1 or me2)
-
-
?
additional information
?
-
enzyme hairless can demethylate monomethylated or dimethylated histone H3 lysine 9 (H3K9me1 or me2)
-
-
?
additional information
?
-
histone H3 N6,N6,N6-trimethyl-L-lysine9 is no substrate
-
-
?
additional information
?
-
PHF8 demethylates H3K9me1, and if overexpressed also of H3K9me2 and H4K20me1 in endothelial cells, whereas H3K27me1/2 and H3K4me3 are not affected
-
-
?
additional information
?
-
the enzyme also catalyzes the demethylation of histone H3 N6,N6-dimethyl-L-lysine4 and histone H3 N6-methyl-L-lysine4. Histone H3 is the preferred histone substrate of KDM1A compared to histones H2A, H2B, and H4. KDM1A likely contains a histone H3 secondary specificity element on the enzyme surface that contributes significantly to its recognition of substrates and products. Kinetic analysis of full-length histone products against KDM1A. KDM1A requires a minimal substrate corresponding to the first 21 residues of the N-terminal histone H3 tail for efficient demethylation activity
-
-
?
additional information
?
-
JMJD1A epigenetically modifies H3K9me2 in the PPARgamma gene locus
-
-
?
additional information
?
-
enzyme acts additionally as mono-methyl histone H4 lysine 20 demethylase
-
-
?
additional information
?
-
enzyme acts additionally as mono-methyl histone H4 lysine 20 demethylase
-
-
?
additional information
?
-
histone demethylase LSD1 demethylates Lys4 or Lys9 of histone H3 using FAD as cofactor
-
-
?
additional information
?
-
PHF8 exhibits both H3K4 and H3K9 demethylase activity in cells, but recombinant PHF8 exhibits only H3K9me2/1 demethylase activity in vitro
-
-
?
additional information
?
-
the bifunctional enzyme catalyzes the demethylation of H3K4me2/me1 (EC 1.14.99.66) and H3K9me2/me1
-
-
?
additional information
?
-
the bifunctional enzyme catalyzes the demethylation of H3K4me2/me1 (EC 1.14.99.66) and H3K9me2/me1
-
-
?
additional information
?
-
the bifunctional enzyme catalyzes the demethylation of H3K4me2/me1 (EC 1.14.99.66) and H3K9me2/me1, as well as non-histone substrates. Tight-binding nature of the H3/KDM1A interaction, kinetics, overview. No other core histones exhibits inhibition of KDM1A demethylation activity, which is consistent with H3 being the preferred histone substrate of KDM1A versus H2A, H2B, and H4. Kinetic analysis of full-length histone products against KDM1A. KDM1A requires a minimal substrate corresponding to the first 21 residues of the N-terminal histone H3 tail for efficient demethylation activity. Recombinant KDM1A/LSD11 forms a complex in vitro with recombinant transcription factor CoREST
-
-
?
additional information
?
-
the bifunctional enzyme catalyzes the demethylation of H3K9me2/me1 and H3K27me3/me2 (EC 1.14.11.68), as well as monomethylated histone H4 Lys20 residue (H4K20Me1). PHF8 acts upstream of KDM3A to regulate specific hypoxia-induced NED markers
-
-
?
additional information
?
-
the bifunctional enzyme catalyzes the demethylation of H3K9me2/me1 and H3K27me3/me2 (EC 1.14.11.68), as well as monomethylated histone H4 Lys20 residue (H4K20Me1). PHF8 acts upstream of KDM3A to regulate specific hypoxia-induced NED markers
-
-
?
additional information
?
-
the bifunctional enzyme catalyzes the demethylation of H3K9me2/me1 and H3K4me2/me1 (1.14.99.66)
-
-
?
additional information
?
-
the bifunctional enzyme catalyzes the demethylation of H3K9me2/me1 and H3K4me2/me1 (EC 1.14.99.66)
-
-
?
additional information
?
-
the bifunctional enzyme catalyzes the demethylation of H3K9me2/me1 and H3K4me2/me1 (EC 1.14.99.66)
-
-
?
additional information
?
-
the bifunctional enzyme catalyzes the demethylation of H3K9me2/me1 and H3K4me2/me1 (EC 1.14.99.66)
-
-
?
additional information
?
-
the bifunctional enzyme catalyzes the demethylation of H3K9me2/me1 and H3K4me2/me1 (EC 1.14.99.66)
-
-
?
additional information
?
-
the bifunctional enzyme catalyzes the demethylation of H3K9me2/me1 and H3K4me2/me1 (EC 1.14.99.66)
-
-
?
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
-
-
?
additional information
?
-
the bifunctional enzyme catalyzes the demethylation of H3K9me2/me1 and H3K9me3/me2 (EC 1.14.11.66)
-
-
?
additional information
?
-
-
no activity with [histone H3]-N6,N6,N6-trimethyl-L-lysine9
-
-
-
additional information
?
-
no activity with [histone H3]-N6,N6,N6-trimethyl-L-lysine9
-
-
-
additional information
?
-
Kdm3a can specifically remove mono- or di-methyl residues from H3K9me1 or H3K9me2 to regulate gene transcription
-
-
?
additional information
?
-
no activity with histone H3 N6,N6,N6-trimethyl-L-lysine9
-
-
?
additional information
?
-
-
enzyme additionally mediates arginine demethylation of H4R3me2s and its intermediate, H4R3me1. Demethylation of H4R3me2s and H3K9me2s in promoter regions is correlated with active gene expression
-
-
?
additional information
?
-
the bifunctional enzyme catalyzes the demethylation of H3K4me2/me1 (EC 1.14.99.66) and H3K9me2/me1
-
-
?
additional information
?
-
the bifunctional enzyme catalyzes the demethylation of H3K9me2/me1 and H3K4me2/me1 (EC 1.14.99.66)
-
-
?
additional information
?
-
the bifunctional enzyme catalyzes the demethylation of H3K9me2/me1 and H3K4me2/me1 (EC 1.14.99.66)
-
-
?
additional information
?
-
JMJD1A epigenetically modifies H3K9me2 in the PPARgamma gene locus
-
-
?
additional information
?
-
JMJD1A epigenetically modifies H3K9me2 in the PPARgamma gene locus
-
-
?
additional information
?
-
-
dynamic nature of histone methylation regulation on four of the main lysine sites of methylation on histone H3 and H4 tails, i.e. H3K4, H3K9, H3K27 and H3K36, overview. Methylation of non-histone proteins may be a general means to regulate epigenetic information
-
-
?
additional information
?
-
lack of in-vitro H3K4 demethylase activity of the Swm1/2 complex
-
-
?
additional information
?
-
lack of in-vitro H3K4 demethylase activity of the Swm1/2 complex
-
-
?
additional information
?
-
-
lack of in-vitro H3K4 demethylase activity of the Swm1/2 complex
-
-
?
additional information
?
-
lack of in-vitro H3K4 demethylase activity of the Swm1/2 complex
-
-
?
additional information
?
-
lack of in-vitro H3K4 demethylase activity of the Swm1/2 complex
-
-
?
additional information
?
-
-
the enzyme KDM3A is associated with Neurog2 protein, but not Ascl1 protein. Neurog2 recruits the enzyme to demethylate [histone H3]-N6,N6-dimethyl-L-lysine9 at the neurod1 promoter
-
-
-
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NATURAL SUBSTRATE
NATURAL PRODUCT
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate)
(Substrate)
LITERATURE
(Substrate)
(Substrate)
COMMENTARY
(Product)
(Product)
LITERATURE
(Product)
(Product)
REVERSIBILITY
r=reversible
ir=irreversible
?=not specified
r=reversible
ir=irreversible
?=not specified
a [histone H3]-N6,N6-dimethyl-L-lysine9 + 2 2-oxoglutarate + 2 O2
a [histone H3]-L-lysine9 + 2 succinate + 2 formaldehyde + 2 CO2
a [histone H3]-N6,N6-dimethyl-L-lysine9 + 2-oxoglutarate + O2
a [histone H3]-N6-methyl-L-lysine9 + succinate + formaldehyde + CO2
a [histone H3]-N6-methyl-L-lysine9 + 2-oxoglutarate + O2
a [histone H3]-L-lysine9 + succinate + formaldehyde + CO2
histone H3 N6,N6,N6-trimethyl-L-lysine9 + 2-oxoglutarate + O2
histone H3 N6,N6-dimethyl-L-lysine9 + succinate + formaldehyde + CO2
histone H3 N6,N6-dimethyl-L-lysine9 + 2-oxoglutarate + O2
histone H3 N6-methyl-L-lysine9 + succinate + formaldehyde + CO2
histone H3 N6-methyl-L-lysine9 + 2-oxoglutarate + O2
histone H3 L-lysine9 + succinate + formaldehyde + CO2
histone H4 N6-methyl-L-lysine20 + 2-oxoglutarate + O2
histone H4 L-lysine20 + succinate + formaldehyde + CO2
-
-
-
?
protein 6-N,6-N-dimethyl-L-lysine + 2-oxoglutarate + O2
protein 6-N-methyl-L-lysine + succinate + formaldehyde + CO2
-
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
-
LSD1 relieves repressive histone marks by demethylation of histone H3 at lysine 9, thereby leading to derepression of androgen receptor target genes
-
-
?
[histone H3]-N6,N6,N6-trimethyl-L-lysine4 + 2-oxoglutarate + O2
[histone H3]-L-lysine4 + succinate + formaldehyde + CO2
-
-
-
-
?
[histone H3]-N6,N6-dimethyl-L-lysine 4 + 2-oxoglutarate + O2
[histone H3]-N6-methyl-L-lysine 4 + succinate + formaldehyde + CO2
-
-
-
?
[histone H3]-N6,N6-dimethyl-L-lysine 9 + 2-oxoglutarate + O2
[histone H3]-N6-methyl-L-lysine 9 + succinate + formaldehyde + CO2
[histone H3]-N6,N6-dimethyl-L-lysine27 + 2-oxoglutarate + O2
[histone H3]-N6-methyl-L-lysine27 + succinate + formaldehyde + CO2
-
-
-
?
[histone H3]-N6,N6-dimethyl-L-lysine4 + 2-oxoglutarate + O2
[histone H3]-L-lysine4 + succinate + formaldehyde + CO2
-
LSD1 is associated with protein BHC80. Upon demethylation of H3K4me2 to H3K4me0 by LSD1/KDM1, BHC80 binds the demethylation product H3K4me0 to maintain LSD1/KDM1 at target loci and to prevent re-methylation of H3K4
-
-
?
[histone H3]-N6,N6-dimethyl-L-lysine9 + 2 2-oxoglutarate + 2 O2
[histone H3]-L-lysine9 + 2 succinate + 2 formaldehyde + 2 CO2
[histone H3]-N6,N6-dimethyl-L-lysine9 + 2-oxoglutarate + O2
[histone H3]-N6-methyl-L-lysine9 + succinate + formaldehyde + CO2
[histone H3]-N6-methyl-L-lysine 4 + 2-oxoglutarate + O2
[histone H3]-L-lysine 4 + succinate + formaldehyde + CO2
-
-
-
?
[histone H3]-N6-methyl-L-lysine 9 + 2-oxoglutarate + O2
[histone H3]-L-lysine 9 + succinate + formaldehyde + CO2
[histone H3]-N6-methyl-L-lysine9 + 2-oxoglutarate + O2
[histone H3]-L-lysine9 + succinate + formaldehyde + CO2
a [histone H3]-N6,N6-dimethyl-L-lysine9 + 2 2-oxoglutarate + 2 O2
a [histone H3]-L-lysine9 + 2 succinate + 2 formaldehyde + 2 CO2
-
-
-
?
a [histone H3]-N6,N6-dimethyl-L-lysine9 + 2 2-oxoglutarate + 2 O2
a [histone H3]-L-lysine9 + 2 succinate + 2 formaldehyde + 2 CO2
-
overall reaction
-
-
?
a [histone H3]-N6,N6-dimethyl-L-lysine9 + 2-oxoglutarate + O2
a [histone H3]-N6-methyl-L-lysine9 + succinate + formaldehyde + CO2
-
-
-
?
a [histone H3]-N6,N6-dimethyl-L-lysine9 + 2-oxoglutarate + O2
a [histone H3]-N6-methyl-L-lysine9 + succinate + formaldehyde + CO2
-
-
-
-
?
a [histone H3]-N6-methyl-L-lysine9 + 2-oxoglutarate + O2
a [histone H3]-L-lysine9 + succinate + formaldehyde + CO2
-
-
-
?
a [histone H3]-N6-methyl-L-lysine9 + 2-oxoglutarate + O2
a [histone H3]-L-lysine9 + succinate + formaldehyde + CO2
-
-
-
-
?
histone H3 N6,N6,N6-trimethyl-L-lysine9 + 2-oxoglutarate + O2
histone H3 N6,N6-dimethyl-L-lysine9 + succinate + formaldehyde + CO2
-
-
-
?
histone H3 N6,N6,N6-trimethyl-L-lysine9 + 2-oxoglutarate + O2
histone H3 N6,N6-dimethyl-L-lysine9 + succinate + formaldehyde + CO2
JMJD1A binds to the MALAT1 gene promoter and demethylates histone H3K9 at the MALAT1 gene promoter
-
-
?
histone H3 N6,N6-dimethyl-L-lysine9 + 2-oxoglutarate + O2
histone H3 N6-methyl-L-lysine9 + succinate + formaldehyde + CO2
-
-
-
?
histone H3 N6,N6-dimethyl-L-lysine9 + 2-oxoglutarate + O2
histone H3 N6-methyl-L-lysine9 + succinate + formaldehyde + CO2
-
-
-
?
histone H3 N6,N6-dimethyl-L-lysine9 + 2-oxoglutarate + O2
histone H3 N6-methyl-L-lysine9 + succinate + formaldehyde + CO2
-
-
-
?
histone H3 N6,N6-dimethyl-L-lysine9 + 2-oxoglutarate + O2
histone H3 N6-methyl-L-lysine9 + succinate + formaldehyde + CO2
-
-
-
?
histone H3 N6,N6-dimethyl-L-lysine9 + 2-oxoglutarate + O2
histone H3 N6-methyl-L-lysine9 + succinate + formaldehyde + CO2
-
-
-
?
histone H3 N6,N6-dimethyl-L-lysine9 + 2-oxoglutarate + O2
histone H3 N6-methyl-L-lysine9 + succinate + formaldehyde + CO2
-
-
-
?
histone H3 N6,N6-dimethyl-L-lysine9 + 2-oxoglutarate + O2
histone H3 N6-methyl-L-lysine9 + succinate + formaldehyde + CO2
-
-
-
?
histone H3 N6,N6-dimethyl-L-lysine9 + 2-oxoglutarate + O2
histone H3 N6-methyl-L-lysine9 + succinate + formaldehyde + CO2
-
-
-
?
histone H3 N6,N6-dimethyl-L-lysine9 + 2-oxoglutarate + O2
histone H3 N6-methyl-L-lysine9 + succinate + formaldehyde + CO2
-
PHF8 is able to demethylate H3K9me2 and H3K9me1
-
-
?
histone H3 N6,N6-dimethyl-L-lysine9 + 2-oxoglutarate + O2
histone H3 N6-methyl-L-lysine9 + succinate + formaldehyde + CO2
-
-
-
?
histone H3 N6-methyl-L-lysine9 + 2-oxoglutarate + O2
histone H3 L-lysine9 + succinate + formaldehyde + CO2
-
-
-
-
?
histone H3 N6-methyl-L-lysine9 + 2-oxoglutarate + O2
histone H3 L-lysine9 + succinate + formaldehyde + CO2
-
-
-
?
histone H3 N6-methyl-L-lysine9 + 2-oxoglutarate + O2
histone H3 L-lysine9 + succinate + formaldehyde + CO2
-
-
-
?
histone H3 N6-methyl-L-lysine9 + 2-oxoglutarate + O2
histone H3 L-lysine9 + succinate + formaldehyde + CO2
-
-
-
?
histone H3 N6-methyl-L-lysine9 + 2-oxoglutarate + O2
histone H3 L-lysine9 + succinate + formaldehyde + CO2
-
-
-
?
histone H3 N6-methyl-L-lysine9 + 2-oxoglutarate + O2
histone H3 L-lysine9 + succinate + formaldehyde + CO2
-
-
-
?
[histone H3]-N6,N6-dimethyl-L-lysine 9 + 2-oxoglutarate + O2
[histone H3]-N6-methyl-L-lysine 9 + succinate + formaldehyde + CO2
-
-
-
?
[histone H3]-N6,N6-dimethyl-L-lysine 9 + 2-oxoglutarate + O2
[histone H3]-N6-methyl-L-lysine 9 + succinate + formaldehyde + CO2
-
-
-
?
[histone H3]-N6,N6-dimethyl-L-lysine 9 + 2-oxoglutarate + O2
[histone H3]-N6-methyl-L-lysine 9 + succinate + formaldehyde + CO2
-
-
-
?
[histone H3]-N6,N6-dimethyl-L-lysine 9 + 2-oxoglutarate + O2
[histone H3]-N6-methyl-L-lysine 9 + succinate + formaldehyde + CO2
-
-
-
?
[histone H3]-N6,N6-dimethyl-L-lysine 9 + 2-oxoglutarate + O2
[histone H3]-N6-methyl-L-lysine 9 + succinate + formaldehyde + CO2
-
-
-
?
[histone H3]-N6,N6-dimethyl-L-lysine 9 + 2-oxoglutarate + O2
[histone H3]-N6-methyl-L-lysine 9 + succinate + formaldehyde + CO2
-
-
-
?
[histone H3]-N6,N6-dimethyl-L-lysine 9 + 2-oxoglutarate + O2
[histone H3]-N6-methyl-L-lysine 9 + succinate + formaldehyde + CO2
-
-
-
?
[histone H3]-N6,N6-dimethyl-L-lysine 9 + 2-oxoglutarate + O2
[histone H3]-N6-methyl-L-lysine 9 + succinate + formaldehyde + CO2
-
-
-
?
[histone H3]-N6,N6-dimethyl-L-lysine 9 + 2-oxoglutarate + O2
[histone H3]-N6-methyl-L-lysine 9 + succinate + formaldehyde + CO2
-
-
-
?
[histone H3]-N6,N6-dimethyl-L-lysine 9 + 2-oxoglutarate + O2
[histone H3]-N6-methyl-L-lysine 9 + succinate + formaldehyde + CO2
-
-
-
?
[histone H3]-N6,N6-dimethyl-L-lysine 9 + 2-oxoglutarate + O2
[histone H3]-N6-methyl-L-lysine 9 + succinate + formaldehyde + CO2
-
-
-
?
[histone H3]-N6,N6-dimethyl-L-lysine9 + 2 2-oxoglutarate + 2 O2
[histone H3]-L-lysine9 + 2 succinate + 2 formaldehyde + 2 CO2
overall reaction
-
-
?
[histone H3]-N6,N6-dimethyl-L-lysine9 + 2 2-oxoglutarate + 2 O2
[histone H3]-L-lysine9 + 2 succinate + 2 formaldehyde + 2 CO2
-
the lysine methylase complexes recognize its own reaction products. The H3K9me2 methylases G9A/KMT1C and GLP/KMT1D, can also bind to their reaction product H3K9me2 via their ankyrin repeat domains
-
-
?
[histone H3]-N6,N6-dimethyl-L-lysine9 + 2 2-oxoglutarate + 2 O2
[histone H3]-L-lysine9 + 2 succinate + 2 formaldehyde + 2 CO2
-
-
-
-
?
[histone H3]-N6,N6-dimethyl-L-lysine9 + 2 2-oxoglutarate + 2 O2
[histone H3]-L-lysine9 + 2 succinate + 2 formaldehyde + 2 CO2
overall reaction
-
-
?
[histone H3]-N6,N6-dimethyl-L-lysine9 + 2 2-oxoglutarate + 2 O2
[histone H3]-L-lysine9 + 2 succinate + 2 formaldehyde + 2 CO2
overall reaction
-
-
?
[histone H3]-N6,N6-dimethyl-L-lysine9 + 2 2-oxoglutarate + 2 O2
[histone H3]-L-lysine9 + 2 succinate + 2 formaldehyde + 2 CO2
overall reaction
-
-
?
[histone H3]-N6,N6-dimethyl-L-lysine9 + 2 2-oxoglutarate + 2 O2
[histone H3]-L-lysine9 + 2 succinate + 2 formaldehyde + 2 CO2
-
Jmjd2c is recruited to the P2 promoter region of Mdm2 gene resulting in demethylation of histone H3 lysine 9, as typically found in actively transcribed genes
-
-
?
[histone H3]-N6,N6-dimethyl-L-lysine9 + 2 2-oxoglutarate + 2 O2
[histone H3]-L-lysine9 + 2 succinate + 2 formaldehyde + 2 CO2
-
propagation of the silencing mark, H3K9me3, at the centromeric and Mating type regions requires the RNAi machinery and DNA recognition factors
-
-
?
[histone H3]-N6,N6-dimethyl-L-lysine9 + 2-oxoglutarate + O2
[histone H3]-N6-methyl-L-lysine9 + succinate + formaldehyde + CO2
-
-
-
?
[histone H3]-N6,N6-dimethyl-L-lysine9 + 2-oxoglutarate + O2
[histone H3]-N6-methyl-L-lysine9 + succinate + formaldehyde + CO2
-
-
-
?
[histone H3]-N6,N6-dimethyl-L-lysine9 + 2-oxoglutarate + O2
[histone H3]-N6-methyl-L-lysine9 + succinate + formaldehyde + CO2
-
-
-
?
[histone H3]-N6,N6-dimethyl-L-lysine9 + 2-oxoglutarate + O2
[histone H3]-N6-methyl-L-lysine9 + succinate + formaldehyde + CO2
-
-
-
?
[histone H3]-N6,N6-dimethyl-L-lysine9 + 2-oxoglutarate + O2
[histone H3]-N6-methyl-L-lysine9 + succinate + formaldehyde + CO2
-
-
-
?
[histone H3]-N6-methyl-L-lysine 9 + 2-oxoglutarate + O2
[histone H3]-L-lysine 9 + succinate + formaldehyde + CO2
-
-
-
?
[histone H3]-N6-methyl-L-lysine 9 + 2-oxoglutarate + O2
[histone H3]-L-lysine 9 + succinate + formaldehyde + CO2
-
-
-
?
[histone H3]-N6-methyl-L-lysine 9 + 2-oxoglutarate + O2
[histone H3]-L-lysine 9 + succinate + formaldehyde + CO2
-
-
-
?
[histone H3]-N6-methyl-L-lysine 9 + 2-oxoglutarate + O2
[histone H3]-L-lysine 9 + succinate + formaldehyde + CO2
-
-
-
?
[histone H3]-N6-methyl-L-lysine 9 + 2-oxoglutarate + O2
[histone H3]-L-lysine 9 + succinate + formaldehyde + CO2
-
-
-
?
[histone H3]-N6-methyl-L-lysine 9 + 2-oxoglutarate + O2
[histone H3]-L-lysine 9 + succinate + formaldehyde + CO2
-
-
-
?
[histone H3]-N6-methyl-L-lysine 9 + 2-oxoglutarate + O2
[histone H3]-L-lysine 9 + succinate + formaldehyde + CO2
-
-
-
?
[histone H3]-N6-methyl-L-lysine 9 + 2-oxoglutarate + O2
[histone H3]-L-lysine 9 + succinate + formaldehyde + CO2
-
-
-
?
[histone H3]-N6-methyl-L-lysine 9 + 2-oxoglutarate + O2
[histone H3]-L-lysine 9 + succinate + formaldehyde + CO2
-
-
-
?
[histone H3]-N6-methyl-L-lysine 9 + 2-oxoglutarate + O2
[histone H3]-L-lysine 9 + succinate + formaldehyde + CO2
-
-
-
?
[histone H3]-N6-methyl-L-lysine 9 + 2-oxoglutarate + O2
[histone H3]-L-lysine 9 + succinate + formaldehyde + CO2
-
-
-
?
[histone H3]-N6-methyl-L-lysine9 + 2-oxoglutarate + O2
[histone H3]-L-lysine9 + succinate + formaldehyde + CO2
-
-
-
?
[histone H3]-N6-methyl-L-lysine9 + 2-oxoglutarate + O2
[histone H3]-L-lysine9 + succinate + formaldehyde + CO2
-
-
-
-
?
[histone H3]-N6-methyl-L-lysine9 + 2-oxoglutarate + O2
[histone H3]-L-lysine9 + succinate + formaldehyde + CO2
-
-
-
?
[histone H3]-N6-methyl-L-lysine9 + 2-oxoglutarate + O2
[histone H3]-L-lysine9 + succinate + formaldehyde + CO2
-
-
-
?
[histone H3]-N6-methyl-L-lysine9 + 2-oxoglutarate + O2
[histone H3]-L-lysine9 + succinate + formaldehyde + CO2
-
-
-
?
additional information
?
-
JMJ27 displays H3K9me1/2 demethylase activity both in vitro and in vivo
-
-
?
additional information
?
-
-
dynamic nature of histone methylation regulation on four of the main lysine sites of methylation on histone H3 and H4 tails, i.e. H3K4, H3K9, H3K27 and H3K36, overview. Methylation of non-histone proteins may be a general means to regulate epigenetic information
-
-
?
additional information
?
-
-
dynamic nature of histone methylation regulation on four of the main lysine sites of methylation on histone H3 and H4 tails, i.e. H3K4, H3K9, H3K27 and H3K36, overview. Methylation of non-histone proteins may be a general means to regulate epigenetic information. Upon stimulation, the bivalent domains segregate into either H3K4me3- or H3K27me3 marked genes for activation and repression, respectively
-
-
?
additional information
?
-
-
the PHD domain of human PHF8 interacts with the catalytic core in a manner similar to ceKIAA1718 of Caenorhabditis elegans, and the C-terminal coiled-coil region interacts with the catalytic core. JHDM1a binds methyl H3K36, while PHF8 does not
-
-
?
additional information
?
-
-
identification of multiple enzyme target genes, many of which play important roles in epidermal development, neural function, and transcriptional regulation, consistent with the predicted biological functions of enzyme hairless, HR, genomic target genes of HR, overview
-
-
?
additional information
?
-
identification of multiple enzyme target genes, many of which play important roles in epidermal development, neural function, and transcriptional regulation, consistent with the predicted biological functions of enzyme hairless, HR, genomic target genes of HR, overview
-
-
?
additional information
?
-
KDM1A catalyzes the oxidative demethylation of histone H3K4me1/2 and H3K9me1/2 as well as non-histone substrates
-
-
?
additional information
?
-
-
KDM3A is a histone demethylase that specifically demethylates mono-methylated (me1) and di-methylated (me2) histone H3 lysine 9 (H3K9)
-
-
?
additional information
?
-
KDM3A is a histone demethylase that specifically demethylates mono-methylated (me1) and di-methylated (me2) histone H3 lysine 9 (H3K9)
-
-
?
additional information
?
-
PHF8 demethylates H3K9me1, and if overexpressed also of H3K9me2 and H4K20me1 in endothelial cells, whereas H3K27me1/2 and H3K4me3, the latter being thought to act as anchor for PHF8, are not affected
-
-
?
additional information
?
-
JMJD1A epigenetically modifies H3K9me2 in the PPARgamma gene locus
-
-
?
additional information
?
-
-
no activity with [histone H3]-N6,N6,N6-trimethyl-L-lysine9
-
-
-
additional information
?
-
no activity with [histone H3]-N6,N6,N6-trimethyl-L-lysine9
-
-
-
additional information
?
-
Kdm3a can specifically remove mono- or di-methyl residues from H3K9me1 or H3K9me2 to regulate gene transcription
-
-
?
additional information
?
-
JMJD1A epigenetically modifies H3K9me2 in the PPARgamma gene locus
-
-
?
additional information
?
-
JMJD1A epigenetically modifies H3K9me2 in the PPARgamma gene locus
-
-
?
additional information
?
-
-
dynamic nature of histone methylation regulation on four of the main lysine sites of methylation on histone H3 and H4 tails, i.e. H3K4, H3K9, H3K27 and H3K36, overview. Methylation of non-histone proteins may be a general means to regulate epigenetic information
-
-
?
additional information
?
-
-
the enzyme KDM3A is associated with Neurog2 protein, but not Ascl1 protein. Neurog2 recruits the enzyme to demethylate [histone H3]-N6,N6-dimethyl-L-lysine9 at the neurod1 promoter
-
-
-
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
COFACTOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
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
FAD
dependent on, required for catalysis. THe FAD is noncovalently bound at the amine oxidase domain (AOD)
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
METALS and IONS
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
Fe2+
Fe2+
JMJ27 is a nuclear protein containing a zinc-finger motif and a catalytic JmjC domain with conserved Fe(II) and alpha-ketoglutarate binding sites
Fe2+
-
in presence of Fe2+ and 2-oxoglutarate, Fe2+ sits in the center of the c-PHF8 catalytic core, which consists of nine hydrophobic residues. Binding of 2-oxoglutarate to Fe2+ does not drastically change the conformation, however it causes the side chain of Y257 to turn towards the substrate binding channel, to be in a position to contact the methyl group of K9me2
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
(19E)-N,N'-diethyl-6,12,17,22,27,33-hexaazaoctatriacont-19-ene-1,38-diamine
i.e PG-11144, exhibits competitive inhibition kinetics at concentrations below 0.010 mmol/l. PG-11144 combined with a DNMT inhibitor increases H3K4 methylation and profoundly inhibits growth of established tumors in vivo
(19Z)-N,N'-diethyl-6,12,17,22,27,33-hexaazaoctatriacont-19-ene-1,38-diamine
-
(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
-
(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
-
(25E)-N,N'-diethyl-5,11,17,23,28,33,39,45-octaazapentacont-25-ene-1,50-diamine
-
(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
-
(2Z)-N-[4-(ethylamino)butyl]-N'-(4-[[4-(ethylamino)butyl]amino]butyl)but-2-ene-1,4-diamine
-
7-[(5-aminopentyl)oxy]-6-methoxy-N2,N2,N4,N4-tetramethylquinazoline-2,4-diamine
-
7-[(5-aminopentyl)oxy]-N2-[3-(dimethylamino)propyl]-6-methoxy-N4,N4-dimethylquinazoline-2,4-diamine
-
7-[(5-aminopentyl)oxy]-N4-(1-benzylpiperidin-4-yl)-N2-[3-(dimethylamino)propyl]-6-methoxyquinazoline-2,4-diamine
-
Cd2+
at 0.001-0.005 mM, cadmium induces histone H3 lysine methylation by inhibiting histone demethylase activity on H3K4 and H3K9. 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
DMOG
a small molecule JMJD1A inhibitor. N-oxalglycine dimethyl ester prodrug, DMOG, exerts histone lysine methylating activity in cells
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
-
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; full-length histone H3, which lacks any posttranslational modifications, is a tight-binding, competitive inhibitor of KDM1A demethylation activity with a Ki of 18.9 nM, a value that is approximately 100fold higher than that of the 21-mer peptide of H3. The relative H3 affinity is independent of preincubation time, suggesting that H3 rapidly reaches equilibrium with KDM1A, tight-binding nature of the H3/KDM1A interaction, kinetics, overview. No other core histones exhibits inhibition of KDM1A demethylation activity, which is consistent with H3 being the preferred histone substrate of KDM1A versus H2A, H2B, and H4. Inhibition profiling of full-length histone H3 against KDM1A
-
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
N-(1-benzylpiperidin-4-yl)-6,7-dimethoxy-2-(4-methyl-1,4-diazepan-1-yl)quinazolin-4-amine
-
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
-
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
-
peptide H3K4M
the modified H3 peptide with substitution of Lys4 to Met [H3K4M] is known to be a potent competitive inhibitor of LSD1
-
tranylcypromine
i.e. Parnate, binding structure analysis and modeling, overview. The LSD1-tranylcypromine complex is not completely composed of the five-membered adduct, but partially contains an intermediate. LSD1-flavin is the only place modified by this inhibition
tranylcypromine
an amino oxidase inhibitor, upregulates hTERT expression and telomerase activity concomitant with elevated H3K4me2 levels and H3 acetylation at the hTERT proximal promoter in cancer cells
additional information
KDM1A tolerance for 3-[(3-cholamidopropyl)-dimethylammonio]-1-propanesulfonate (CHAPS) at 0.01% w/v and dimethyl sulfoxide (DMSO) at 10% v/v; no other core histones exhibit inhibition of KDM1A demethylation activity. Kinetic analysis of full-length histone products against KDM1A
-
additional information
structural analysis of homoserine-substituted inhibitor peptide-bound LSD1-CoREST complex, overview
-
additional information
demethylation activity is decreased by other modifications on the H3 tail, such as acetylation and phosphorylation, suggesting possible regulatory mechanisms
-
additional information
small molecule inhibitors of LSD1 inhibit xenograft tumor growth
-
additional information
oligoamine analogues are competitive inhibitors of recombinant LSD1. Oligoamine analogues inhibit lysine-specific demethylase 1 and induce reexpression of epigenetically silenced genes, overview. Treatment of HCT-116 colon adenocarcinoma cells in vitro results in increased H3K4 methylation and reexpression of silenced SFRP genes. This reexpression is also accompanied by a decrease in H3K9me2 repressive mark. Use of LSD1 inhibitors in combination with a DNA methyltransferase (DNMT) inhibitors (5-aza-2'-deoxycitidine and 5-azacytidine) is a combination that is not only more efficacious in reactivating specific aberrantly silenced genes but also leads to profound inhibition of the growth of established human colon cancer xenografts in a nude mouse mode
-
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
-
additional information
biguanide and bisguanidine polyamine analogues are potent inhibitors of LSD1. These analogues inhibit LSD1 in human colon carcinoma cells and affect a reexpression of multiple, aberrantly silenced genes important in the development of colon cancer, including members of the secreted frizzle-related proteins (SFRPs) and the GATA family of transcription factors. Reexpression is concurrent with increased H3K4me2 and acetyl-H3K9 marks, decreased H3K9me1 and H3K9me2 repressive marks. Inhibition detection via global H3K4me1 and H3K4me2 levels. HCT116 cells are exposed to increasing concentrations of the indicated compound for 48 h,and 00.03 mg of nuclear protein per lane is analyzed for expression of H3K4me1, H3K4me2, and H3K9me2, overview. Exposure to compounds 1c and 2d produces significant increases in both H3K4me1 and H3K4me2, without affecting global H3K9me2 levels. H3K9me1 and H3K9me2 levels actually decrease in the promoters of the reexpressed genes
-
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ACTIVATING COMPOUND
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
HP1a
-
Suv(Var)3-9/KMT1 interacts with HP1 that binds [histone H3]-N6,N6-trimethyl-L-lysine9
-
tetrahydrofolate
binding kinetic analysis of folate derivatives, e.g. folates bound to glutamates, the (6R,S) form of the natural pentaglutamate form of tetrahydrofolate bound with the highest affinity to full-length LSD1, binding of different forms of folate to LSD1, and binding structures, overview
additional information
-
local demethylation of H3K9me2 is triggered by recruitment of liganded estrogen receptor ERalpha to chromatin
-
additional information
interleukin-1beta enhances recruitment of LSD1 to mPGES-1 promoter
-
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KM VALUE [mM]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
TURNOVER NUMBER [1/s]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
kcat/KM VALUE [1/mMs-1]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
Ki VALUE [mM]
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY
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, 25°C
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, 25°C
0.0021
7-[(5-aminopentyl)oxy]-N2-[3-(dimethylamino)propyl]-6-methoxy-N4,N4-dimethylquinazoline-2,4-diamine
pH and temperature not specified in the publication
0.0025
7-[(5-aminopentyl)oxy]-N4-(1-benzylpiperidin-4-yl)-N2-[3-(dimethylamino)propyl]-6-methoxyquinazoline-2,4-diamine
pH and temperature not specified in the publication
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, 25°C
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, 25°C
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, 25°C
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, 25°C
0.0153
N-(1-benzylpiperidin-4-yl)-6,7-dimethoxy-2-(4-methyl-1,4-diazepan-1-yl)quinazolin-4-amine
pH and temperature not specified in the publication
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, 25°C
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, 25°C
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, 25°C
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, 25°C
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, 25°C
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, 25°C
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, 25°C
additional information
additional information
kinetic analysis of full-length histone products against KDM1A
-
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IC50 VALUE [mM]
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
0.019
7-[(5-aminopentyl)oxy]-6-methoxy-N2,N2,N4,N4-tetramethylquinazoline-2,4-diamine
Homo sapiens
pH and temperature not specified in the publication
0.0034
7-[(5-aminopentyl)oxy]-N2-[3-(dimethylamino)propyl]-6-methoxy-N4,N4-dimethylquinazoline-2,4-diamine
Homo sapiens
pH and temperature not specified in the publication
0.0037
7-[(5-aminopentyl)oxy]-N4-(1-benzylpiperidin-4-yl)-N2-[3-(dimethylamino)propyl]-6-methoxyquinazoline-2,4-diamine
Homo sapiens
pH and temperature not specified in the publication
0.0165
N-(1-benzylpiperidin-4-yl)-6,7-dimethoxy-2-(4-methyl-1,4-diazepan-1-yl)quinazolin-4-amine
Homo sapiens
pH and temperature not specified in the publication
0.067
N-oxalylglycine
Homo sapiens
pH and temperature not specified in the publication
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pH OPTIMUM
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
7.5
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TEMPERATURE OPTIMUM
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
37
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ORGANISM
COMMENTARY
LITERATURE
UNIPROT
SEQUENCE DB
SOURCE
hypoxia can stimulate enzyme mRNA and protein expression, involving binding of hypoxia-induced factor 1 to a specific hypoxia responsive element in the enzyme's promoter
UniProt
brenda
hypoxia can stimulate enzyme mRNA and protein expression involving binding of hypoxia-induced factor 1 to a specific hypoxia responsive element in the enzyme's promoter
-
brenda
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SOURCE TISSUE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
SOURCE
enzyme JMJD1C is upregulated in patient esophageal cancer tissues and different esophageal cancer cell lines
brenda
during the differentiation of leukemic HL60 cells, the decreased hTERT expression is accompanied by the LSD1 recruitment to the hTERT promoter
brenda
the enzyme is mainly distributed in luminal epithelial cells of wild-type mammary glands
brenda
olfactory-placode-derived cell line, OP-6
brenda
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lysine-specific demethylase 1 colocalizes with androgen receptor
brenda
protein level is the highest in round spermatids, compared with spermatocyte and elogating spermatids
brenda
high expression at both mRNA and protein level, significant increase during spermatogenesis. Expression during and after meiosis, preceding the expression of transition proteins and protamines
brenda
additional information
high basal expression with 2.3-fold increase in mRNA after 6 h of hypoxia
brenda
up-regulation of mRNA and protein after exposure to hypoxia or iron scavengers in vitro. Blocking of hypoxia-inducible factor 1 signaling abrogates the up-regulation
brenda
nuclear extracts of HeLa cells contain LSD1 that is associated with folate
brenda
lysine-specific demethylase 1 is strongly expressed in poorly differentiated neuroblastoma
brenda
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lysine-specific demethylase 1 colocalizes with androgen receptor
brenda
protein level is the highest in round spermatids, compared with spermatocyte and elongating spermatids. Protein is not detectable in spermatogonia or gamma-H2AX-positive early pachytene spermatocytes
brenda
pachytene spermatocytes, JHDM2A signals can be detected in nuclei until the diplotene stage but are weak or absent in round spermatids
brenda
additional information
analysis of temporal and spatial expression of JMJ27
brenda
additional information
mRNA expression is increased in most tissues of human fetuses in whom oxygen supply is low compared to postnatal levels
brenda
additional information
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immunohistochemic analysis of tissue localization, overview
brenda
additional information
immunohistochemic analysis of tissue localization, overview
brenda
additional information
LSD1 microarray transcriptome analysis, overview
brenda
additional information
Kdm3a protein is differentially expressed in the luminal epithelial cells of mouse mammary glands at different ages
brenda
additional information
female nuclei of pachytene as well as leptotene/zygotene oocytes lack JHDM2A signals
brenda
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LOCALIZATION
ORGANISM
UNIPROT
COMMENTARY
GeneOntology No.
LITERATURE
SOURCE
shift of cytoplasmic JMJD1A into the nucleus on hypoxia treatment
brenda
enzyme LSD1 is present at the proximal region of the microsomal PGES-1 promoter
brenda
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LSD1 is present on chromatin in both the presence and the absence of estrogens
brenda
JMJ27 is a nuclear protein containing a zinc-finger motif
brenda
KDM4A predominantly localizes to heterochromatin and regulates heterochromatin position-effect variegation, organization of repetitive DNAs, and DNA repair
brenda
-
brenda
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GENERAL INFORMATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
evolution
malfunction
metabolism
physiological function
additional information
evolution
KDM3A is a histone demethylase in the JmjC domain-containing protein family
evolution
the enzyme belongs to the JHDM2 (JmjC domain-containing histone demethylase 2) family of enzymes which modulates defense against pathogens and flowering time
evolution
the enzyme belongs to the superfamily of flavin adenine dinucleotide (FAD)–dependent amine oxidases
evolution
the hairless (HR) protein contains a Jumonji C (JmjC) domain that is conserved among a family of proteins with histone demethylase (HDM) activity
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
malfunction
knockdown of JMJD1C inhibits esophageal cancer cell proliferation. Knockdown of JMJD1C represses the protein and mRNA levels of YAP1 via regulating the H3K9me2 activity, but not the H3K9me1 activity. Inhibition of EC cell proliferation by the knockdown of JMJD1C is rescued by overexpression of YAP1, YAP1 acts as an oncogene in tumor progression
malfunction
knockdown of KDM7A by a small interfering RNA reduces the ICAM1 protein level and leukocyte adhesion without an effect on ICAM1 mRNA expression. In contrast, a KDM1B knockdown does not affect TNF-alpha-induced ICAM1 expression. Lysosome inhibitors increase the TNF-alpha-induced ICAM1 protein level and restore KDM7A knockdown-induced downregulation of ICAM1. In contrast, the KDM7A knockdown has no effect on proteasome-mediated ICAM1 degradation, but knockdown of KDM7A enhances CHX-induced ICAM1 protein degradation
malfunction
knockout of Kdm3a increases H3K9me1 and H3K9me2 in the mammary epithelial cells. Knockout of Kdm3a results in retarded mammary gland ductal growth. Comparison of mammary gland ductal morphogenesis in wild-type and Kdm3a knockout virgin mice, overview. Kdm3a knockout shows no obvious effect on mammary gland tumor initiation but significantly reduces tumor growth
malfunction
loss of JMJ27 function leads to early flowering. Expression of PR genes is compromised in jmj27 mutants. Loss of JMJ27 function leads to hypermethylation of histones (H3) at PR1 and WRKY25 promoters, mutant phenotypes, overview. No significant difference is observed at the FT locus in jmj27 mutants compared with the wild-type, indicating that JMJ27 does not modulate H3K9me2 levels at this locus
malfunction
overexpression of PHF8 catalyzes the removal of methyl-groups from histone 3 lysine 9 (H3K9) and H4K20, whereas knockdown of the enzyme increases H3K9 methylation. Knockdown of PHF8 by RNAi also attenuates endothelial proliferation and survival. Enzyme knockout by PHF8 siRNA attenuates the capacity for migration and developing of capillary-like structures
malfunction
PHF8 knockdown induces DNA damage and apoptosis in lung cancer cells. miR-21 knockdown blocks the effects of PHF8 on proliferation and apoptosis of lung cancer cells. Cell proliferation and colonyforming activity are markedly reduced when PHF8 is knocked down in A-549, LC-AI, and NCI-H292 cells
malfunction
RNAi-mediated knockdown of KDM3A substantially reduces apoptosis following detachment and, conversely, ectopic expression of KDM3A induces cell death in attached cells. Knockdown of Kdm3a enhances metastatic potential in a mouse model of breast cancer metastasis. Defective KDM3A expression in human breast cancer cell lines and tumors. Kdm3a knockdown significantly increases the number of cells that survived in the mouse lung relative to the control NS shRNA
malfunction
The jmj24-3 mutation can partially complement ibm1 for phenotypic and gene expression defects
malfunction
two missense mutations in gene HR in patients with atrichia with papular lesions abolish the demethylase activity of the enzyme, demonstrating the role of enzyme HR demethylase activity in human disease. Various missense mutations, e.g. mutations D1012N or V1056M, in the HR JmjC domain are associated with atrichia with papular lesions (APL)
malfunction
depletion of LSD1 in an immortalized olfactory-placode-derived cell line (OP6) results in multigenic and multiallelic odorant receptor (OR) transcription per cell, while not seemingly disrupting the ability of these cells to activate new OR genes during clonal expansion. LSD1 depletion does not seem to alter OR representation in OP6 cell populations. Apparent systematic accumulation of H3K4me2 (and possibly H3K9me2) in LSD1-depleted cell populations
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
malfunction
Differentiation of neuroblastoma cells results in down-regulation of LSD1. Small interfering RNA-mediated knockdown of LSD1 decreases cellular growth, induces expression of differentiation-associated genes, and increases target gene-specific H3K4 methylation. LSD1 inhibition using monoamine oxidase inhibitors results in an increase of global H3K4 methylation and growth inhibition of neuroblastoma cells in vitro. Small molecule inhibitors of LSD1 inhibit xenograft tumor growth
malfunction
downregulation of the expression of JMJD1A using small interfering or short hairpin RNAs. JMJD1A knockdown in hepatic stellate cells correlates with reinforced dimethylated lysine in histone H3, H3K9me2, in the PPARgamma gene promoter. JMJD1A downregulation in both mRNA and protein leads to increased expression of fibrosis markers, which can be consistently rescued by JMJD1A overexpression
malfunction
genome-wide changes in patterns of histone methylation are correlated with gene expression upon deletion of the swm1+ gene. In vivo, loss of Swm1 increases the global levels of both H3K9me2 and H3K4me2. A significant accumulation of H3K4me2 is observed at genes that are up-regulated in a swm1 deletion strain. In addition, H3K9me2 accumulates at some genes known to be direct Swm1/2 targets that are down-regulated in the swm1DELTA strain. The lack of in-vitro H3K4 demethylase activity of the Swm1/2 complex, suggests that the increased H3K4me2 levels results from either increased H3K4 methylation via Set1, or the incorporation of H3K4 methylated histones during transcription
malfunction
in normal human fibroblasts with a tight hTERT repression, a pharmacological inhibition of LSD1 leads to a weak hTERT expression, and a robust induction of hTERT mRNA occurs when LSD1 and histone deacetylases are both inhibited. Small interference RNA-mediated depletion of both LSD1 and CoREST, a co-repressor in HDAC-containing complexes, synergistically activate hTERT transcription. In cancer cells, inhibition of LSD1 activity or knocking-down of its expression lead to significant increases in levels of hTERT mRNA and telomerase activity, phenotype, overview
malfunction
in vivo, loss of Swm1 increases the global levels of both H3K9me2 and H3K4me2. A significant accumulation of H3K4me2 is observed at genes that are up-regulated in a swm1 deletion strain. In addition, H3K9me2 accumulates at some genes known to be direct Swm1/2 targets that are down-regulated in the swm1DELTA strain
malfunction
inhibition of LSD1 by polyamine analogues increases activating H3K4me2 and acetyl H3K9 marks and decreases repressive H3K9me1 and H3K9me2 marks at the promoters of reexpressed genes
malfunction
Jmjd1a depletion leads to embryonic stem cell differentiation, which is accompanied by a reduction in the expression of embryonic stem cell-specific genes and an induction of lineage marker genes. The level of H3K9Me2, but not H3K9Me3, of total cell histone H3, is increased upon Jmjd1a knockdown. Knockdown of Jmjd1a does not appreciably affect Jmjd2c and vice versa
malfunction
JMJD1A knockdown in hepatic stellate cells correlates with reinforced H3K9me2 in the PPARgamma gene promoter, and its downregulation in both mRNA and protein leads to increased expression of fibrosis markers, which can be consistently rescued by JMJD1A overexpression. Jmjd1a knockdown in situ results in significantly increased expression of alpha-smooth muscle actin and Col1a, strengthened production of collagens, and remarkably enhanced necrosis 4 weeks after treatment. JMJD1A knockdown using si-JMJD1A-1 and si-JMJD1A-2 results in significantly decreased expression of PPARgamma but does not affect the expression of other PPAR signaling members, JMJD1A may modulate PPARgamma expression in liver HSCs in a cell type-specific manner
malfunction
knockdown of LSD1 diminishes LSD1 occupancy on the IL1beta and the IL6 promoter, while promoter occupancy on those promoters cannot be detected with an IgG control antibody. Inhibition of LSD1 by an siRNA approach is accompanied by an increase of the active histone mark H3K4me2 and a decrease in the repressive H3K9me2 mark, resulting in activation of IL1beta and IL6 genes after LSD1 silencing
malfunction
PHF8 knockout inhibits the hypoxic activation of HIF1alpha protein, and attenuates the upregulation of KDM3A and ENO2 proteins. The fact that PHF8 knockdown by shRNAs in LNCaP cells does not affect HIF1A mRNA when compared with the impaired activation of HIF1alpha protein suggests that PHF8 indirectly regulates HIF1alpha protein
malfunction
treatment of HCT-116 colon adenocarcinoma cells with oligoamine analogues inhibitors in vitro results in increased H3K4 methylation and reexpression of silenced SFRP genes. This reexpression is also accompanied by a decrease in H3K9me2 repressive mark
malfunction
an enzyme mutation causes a very severe growth phenotype with a much reduced plant size
malfunction
-
enzyme depletion results in defective primary neurogenesis in early Xenopus embryos
malfunction
switching off the enzyme in cancer cells increases their ability to move around the body
malfunction
-
downregulation of the expression of JMJD1A using small interfering or short hairpin RNAs. JMJD1A knockdown in hepatic stellate cells correlates with reinforced dimethylated lysine in histone H3, H3K9me2, in the PPARgamma gene promoter. JMJD1A downregulation in both mRNA and protein leads to increased expression of fibrosis markers, which can be consistently rescued by JMJD1A overexpression
-
malfunction
-
genome-wide changes in patterns of histone methylation are correlated with gene expression upon deletion of the swm1+ gene. In vivo, loss of Swm1 increases the global levels of both H3K9me2 and H3K4me2. A significant accumulation of H3K4me2 is observed at genes that are up-regulated in a swm1 deletion strain. In addition, H3K9me2 accumulates at some genes known to be direct Swm1/2 targets that are down-regulated in the swm1DELTA strain. The lack of in-vitro H3K4 demethylase activity of the Swm1/2 complex, suggests that the increased H3K4me2 levels results from either increased H3K4 methylation via Set1, or the incorporation of H3K4 methylated histones during transcription
-
malfunction
-
genome-wide changes in patterns of histone methylation are correlated with gene expression upon deletion of the swm1+ gene. In vivo, loss of Swm1 increases the global levels of both H3K9me2 and H3K4me2. A significant accumulation of H3K4me2 is observed at genes that are up-regulated in a swm1 deletion strain. In addition, H3K9me2 accumulates at some genes known to be direct Swm1/2 targets that are down-regulated in the swm1DELTA strain. The lack of in-vitro H3K4 demethylase activity of the Swm1/2 complex, suggests that the increased H3K4me2 levels results from either increased H3K4 methylation via Set1, or the incorporation of H3K4 methylated histones during transcription
-
malfunction
-
The jmj24-3 mutation can partially complement ibm1 for phenotypic and gene expression defects
-
metabolism
identification of a pathway through which N-Myc causes neuroblastoma cell migration and invasion, N-Myc modulates target gene expression partly through up-regulating JMJD1A gene expression
metabolism
demethylation activity is decreased by other modifications on the H3 tail, such as acetylation and phosphorylation, suggesting possible regulatory mechanisms
metabolism
expression of histone H3 Lys 9 demethylases Jmjd1a and Jmjd2c (EC 1.14.11.66) is positively correlated with the pluripotent state of ES and iPS cells. Jmjd1a and Jmjd2c regulate the global levels of H3K9Me2 and H3K9Me3, respectively
metabolism
genetic exist links between lysine-specific demethylases, the histone deacetylase Clr6, and the chromatin remodeller Hrp1. Complex interactions between histone demethylase, deacetylase and chromatin remodelling activities in the regulation of gene expression
metabolism
JMJD1A as an epigenetic regulator that modulates hepatic stellate cell activation and liver fibrosis through targeting PPARgamma gene expression, molecular mechanism, overview
metabolism
JMJD1A as an epigenetic regulator that modulates hepatic stellate cell activation and liver fibrosis through targeting PPARgamma gene expression, molecular mechanism, overview
metabolism
LincRNAFEZF1-AS1 represses p21 expression to promote gastric cancer proliferation through LSD1-mediated H3K4me2 demethylation. FEZF1-AS1 recruits and binds to LSD1 to epigenetically repress downstream gene p21, thereby promoting proliferation in advanced stages of gastric cancer. FEZF1-AS1 is a long non-coding RNA (lncRNA) producing a 2564 bp transcript, located in chromosome 7. FEZF1-AS1 upregulation is associated with tumor size, stage and poor survival of gastric cancer patients. FEZF1-AS1 promotes gastric cancer cells proliferation in vitro and vivo
metabolism
-
JMJD1A as an epigenetic regulator that modulates hepatic stellate cell activation and liver fibrosis through targeting PPARgamma gene expression, molecular mechanism, overview
-
metabolism
-
genetic exist links between lysine-specific demethylases, the histone deacetylase Clr6, and the chromatin remodeller Hrp1. Complex interactions between histone demethylase, deacetylase and chromatin remodelling activities in the regulation of gene expression
-
metabolism
-
genetic exist links between lysine-specific demethylases, the histone deacetylase Clr6, and the chromatin remodeller Hrp1. Complex interactions between histone demethylase, deacetylase and chromatin remodelling activities in the regulation of gene expression
-
physiological function
-
H3 histone methylation and demethylation controls expression of estrogen-responsive genes, and DNA-bound estrogen receptor directs transcription by participating in bending chromatin to contact the RNA polymerase II recruited to the promoter driven by receptor-targeted demethylation of H3 lysine 9 through LSD1 at both enhancer and promoter sites, molecular mechanism, overview. The produced hydrogen peroxide, which modifies the surrounding DNA and recruits 8-oxoguanine–DNA glycosylase 1 and topoisomerase IIb, triggering chromatin and DNA conformational changes that are essential for estrogen-induced transcription
physiological function
-
histone methylation at H3K9 and demethylation at H3K4 play a role in the recruitment of DNA methylases. Co-existence of H3K4me3, an active methyl mark, and H3K27me3, a repressive mark, on developmentally important genes in stem cells
physiological function
methylation on the N-terminal tails of histone lysines serves as an epigenetic control mechanism, which is regulated by demathylases
physiological function
dimethylation of histone H3 lysine 9 (H3K9me2) is a heterochromatic mark linked to DNA methylation and gene repression. Removal of H3K9me2 from gene bodies by the jmjC histone demethylase JMJ25 inhibits DNA methylation and derepresses gene expression. JmjC domain protein JMJ24 antagonizes histone H3K9 demethylase IBM1/JMJ25 function and interacts with RNAi pathways for gene silencing
physiological function
epithelial cells that lose attachment to the extracellular matrix (ECM), or attach to an inappropriate ECM, undergo a specialized form of apoptosis called anoikis. Anoikis has an important role in preventing oncogenesis, particularly metastasis, by eliminating cells that lack proper ECM cues. Histone H3K9 demethylase KDM3A promotes anoikis by transcriptionally activating pro-apoptotic genes BNIP3 and BNIP3L. KDM3A demethylates H3K9me1/2 to stimulate expression of one or more pro-apoptotic genes. KDM3A promotes anoikis through transcriptional activation of BNIP3 and BNIP3L, which encode pro-apoptotic proteins. Identification of KDM3A as an anoikis effector in breast cancer epithelial cells, overview
physiological function
histone demethylase JMJD1A activates gene transcription by demethylating the lysine 9 residue of histone H3 (H3K9) at target gene promoters. Enzyme JMJD1A induces cell migration and invasion by up-regulating the expression of the long noncoding RNA MALAT1. JMJD1A and MALAT1 induce, while the small molecule JMJD1A inhibitor DMOG suppresses, neuroblastoma cell migration and invasion. The long noncoding RNA MALAT1 induces lung cancer cell migration and plays a pivotal role in lung cancer metastasis. JMJD1A induces neuroblastoma cell migration and invasion. Enzyme JMJD1A directly binds to promoter regions of beta-adrenergic agonist target genes such as Ucp1, demethylates histone H3K9 at the promoters, and activates gene transcription. Genome-wide analysis reveals that JMJD1A siRNA-1 reduces the expression of 0.15% (63 probes/41717 probes) of genes, but upregulated the expression of 0.67% (280 probes/41717 probes) of genes. 1.59% (1 probe/63 probes) of genes downregulated by JMJD1A siRNA-1 are up-regulated by N-Myc siRNA-1, 7.94% (5 probes/63 probes) of genes downregulated by JMJD1A siRNA-1 are also downregulated by N-Myc siRNA-1
physiological function
histone demethylase JMJD1C regulates esophageal cancer proliferation via YAP1 signaling. JMJD1C controls the proliferation of esophageal cancer via modulation of H3K9me2 activity, targeting the YAP1 gene expression and functions as a tumor suppressor in esophageal cancer. JMJD1C levels are positively correlated with the TNM stage
physiological function
histone demethylase KDM7A mediates TNF-alpha-induced ICAM1 protein upregulation by modulating lysosomal activity. KDM7A-mediated ICAM1 protein upregulation is likely related to protein stability, not a histone-mediated epigenetic mechanism, role of KDM7A in ICAM1 protein stabilization via a lysosome-dependent pathway, overview
physiological function
histone modification alters chromatin architecture to regulate gene transcription. It removes di- and mono-methyl residues from di- or mono-methylated lysine 9 of histone H3 (H3K9me2/me1). Histone demethylase Kdm3a is required for normal epithelial proliferation ductal elongation and tumor growth in the mouse mammary gland. Kdm3a is not required for estrogen-induced ductal growth in the mammary gland. Kdm3a is required for normal proliferation and cyclin D1 expression in the mammary gland epithelial cells during the pubertal fast growing phase of mammary gland development. Kdm3a plays a direct role in upregulating cyclin D1 expression
physiological function
identification of multiple enzyme target genes, many of which play important roles in epidermal development, neural function, and transcriptional regulation, consistent with the predicted biological functions of enzyme hairless, HR. Hairless, HR, is a H3K9 demethylase that regulates epidermal homeostasis via direct control of its target genes
physiological function
JMJ27 displays H3K9me1/2 demethylase activity both in vitro and in vivo. JMJ27 is induced in response to virulent Pseudomonas syringae pathogens and is required for resistance against these pathogens. JMJ27 is a negative modulator of WRKY25 (a repressor of defense) and a positive modulator of several pathogenesis-related (PR) proteins. It negatively modulates the major flowering regulator Constans (CO) and positively modulates Flowering locus C (FLC). JMJ27 functions as a histone demethylase to modulate both physiological (defense) and developmental (flowering time) processes in Arabidopsis. JMJ27 negatively modulates expression of WRKY genes. JMJ27 modulates flowering time by regulating expression of major flowering time genes through modulating histone methylation
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
physiological function
PHF8 is a JmjC domain-containing protein and erases repressive histone marks including H4K20me1 and H3K9me1/2. It binds to H3K4me3, an active histone mark usually located at transcription start sites (TSSs), through its plant homeo-domain, and is thus recruited and enriched in gene promoters. PHF8 is involved in the development of several types of cancer, including leukemia, prostate cancer, and esophageal squamous cell carcinoma. PHF8 promotes miR-21 expression in human lung cancer, and PHF8 promotes lung cancer cell growth and survival by regulating miR-21. PHF8 is an oncogenic protein in human non-small cell lung cancer (NSCLC) and is upregulated in human NSCLC tissues. PHF8 regulates lung cancer cell growth and transformation. High PHF8 expression predicts poor survival
physiological function
the enzyme catalyzes the oxidative demethylation of histone H3K4me1/2 and H3K9me1/2 repressing and activating transcription, respectively. Although the enzyme itself is sufficient for demethylation of peptide and histone substrates, activity toward nucleosomes in vitro is regulated by its interaction with CoREST, the minimal portion of which contains the linker and SANT2 domain or possibly the SANT1 domain
physiological function
the histone demethylase PHF8 is essential for endothelial cell migration and regulates brain and craniofacial development. Enzyme PHF8 controls the endothelial gene repressor E2F4. PHF8 maintains E2F4 but not E2F1 expression in endothelial cells. Chromatin immunoprecipitation reveals that PHF8 reduces the H3K9me2 level at the E2F4 transcriptional start site, demonstrating a direct function of PHF8 in endothelial E2F4 gene regulation. PHF8, by controlling E2F4 expression, maintains endothelial function
physiological function
ectopic expression of wild-type, but not JmjC-mutant protein, leads to pronounced demethylation of H3K9 in cultured human HeLa cells and modulates expression of genes involved in hair biology, neural activity, and cell cycle and transcriptionalregulation
physiological function
enzyme LSD1 participates in development and differentiation regulation of chromatin remodeling and histone demethylation, and specifically catalyses the demethylation of mono- and di-methylated histone H3 lysine 4 (H3K4) and H3 lysine 9 (H3K9) through a redox process. LSD1 directly binds to the promoter of P21 where it catalyzes H3K4me2 demethylation
physiological function
enzyme specifically demethylates mono- and dimethyl-histone 3 at residue K9. A JmjC domain and a zinc finger present in JHDM2A are required for its enzymatic activity. Overexpression of JHDM2A greatly reduces the H3K9 methylation level in vivo. Knockdown of JHDM2A results in an increase in the dimethyl-K9 levels at the promoter region of a subset of genes concomitant with decrease in their expression. JHDM2A exhibits hormone-dependent recruitment to androgen-receptor target genes, resulting in H3K9 demethylation and transcriptional activation
physiological function
fission yeast proteins Swm1 and Swm2 (after SWIRM1 and SWIRM2), associate together in a complex. This complex specifically demethylates lysine 9 in histone H3 (H3K9) and both up- and down-regulates expression of different groups of genes.Lack of in-vitro H3K4 demethylase activity of the Swm1/2 complex suggesting that the increased H3K4me2 levels results from either increased H3K4 methylation via Set1, or the incorporation of H3K4 methylated histones during transcription
physiological function
function of the mammalian olfactory system depends on specialized olfactory sensory neurons (OSNs) that each express only one allele of one odorant receptor (OR) gene (monogenic). The lysine-specific demethylase-1 (LSD1) has a role in silencing additional OR alleles in the immortalized olfactory-placode-derived cell line (OP6) cellular context. LSD1 protein removes activating H3K4 or silencing H3K9 methylation marks in a variety of developmental contexts
physiological function
histone demethylase PHF8 plays an essential role in hypoxia signaling. Knockdown or knockout of PHF8 reduces the activation of HIF1alpha and the induction of HIF1alpha target genes including KDM3A. PHF8 regulates hypoxia inducible genes mainly through sustaining the level of trimethylated histone 3 lysine 4 (H3K4me3). The positive role of PHF8 in hypoxia signaling extends to hypoxia-induced neuroendocrine differentiation, wherein PHF8 cooperates with KDM3A to regulate the expression of neuroendocrine differentiation genes. The role of PHF8 in hypoxia signaling is associated with the presence of full-length androgen receptor in castration-resistant prostate cancer cells
physiological function
histone demethylase PHF8 regulates hypoxia signaling through HIF1alpha and H3K4me3. Enzyme PHF8 binds and stabilizes histone H3 N6,N6,N6-trimethyl-L-lysine4, PHF8 is important in maintaining H3K4me3 levels on hypoxia-inducible genes, regulation, overview. PHF8 cooperates with KDM3A (EC 1.14.11.65) and PHF8 plays a role in hypoxia signaling. The regulation of hypoxia signaling by PHF8 is associated with androgen receptor AR status in prostate cancer cells
physiological function
histone H3K9 demethylase JMJD1A modulates hepatic stellate cells activation and liver fibrosis by epigenetically regulating peroxisome proliferator-activated receptor gamma (PPARgamma), molecular mechanism, overview
physiological function
histone H3K9 demethylase JMJD1A modulates hepatic stellate cells activation and liver fibrosis by epigenetically regulating peroxisome proliferator-activated receptor gamma, molecular mechanism, overview
physiological function
in attached breast epithelial cells, KDM3A expression is maintained at low levels by integrin signaling. Following detachment, integrin signaling is decreased resulting in increased KDM3A expression. Knockdown of KDM3A substantially reduces apoptosis following detachment and, ectopic expression of KDM3A induces cell death in attached cells. KDM3A promotes anoikis through transcriptional activation of BNIP3 and BNIP3L, which encode pro-apoptotic proteins
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
physiological function
Jhdm2a is critically important in regulating the expression of metabolic genes. The loss of Jhdm2a function results in obesity and hyperlipidemia in mice. The loss of Jhdm2a function disrupts beta-adrenergic-stimulated glycerol release and oxygen consumption in brown fat, and decreases fat oxidation and glycerol release in skeletal muscles. Jhdm2a directly regulates peroxisome proliferator-activated receptor alpha (Ppara) and Ucp1 expression. beta-Adrenergic activation-induced binding of Jhdm2a to the PPAR responsive element (PPRE) of the Ucp1 gene decreases levels of H3K9me2 (dimethylation of lysine 9 of histone H3) at the PPRE
physiological function
Jmjd1a binds myocardin-related transcription factor-A, and the jumonjiC domain of Jmjd1a is sufficient to mediate this interaction. Overexpression of Jmjd1a in multipotential 10T1/2 cells decreases global levels of dimethyl H3K9, stimulates alpha-actin and SM22 promoters, and synergistically enhances MRTF-A- and myocardin-dependent transactivation. TGF-beta-mediated upregulation of smooth muscle cell differentiation marker gene expression in 10T1/2 cells is associated with decreased H3K9 dimethylation at the CArG-containing regions of the smooth muscle cell differentiation marker gene promoters. Knockdown of Jmjd1a in 10T1/2 cells and primary rat aortic smooth muscle cells attenuates TGF-beta-induced upregulation of endogenous smooth muscle myosin heavy chain expression concomitant with increased H3K9 dimethylation at the differentiation marker gene promoters
physiological function
Jmjd1a depletion leads to embryonic stem cell differentiation, which is accompanied by a reduction in the expression of embryonic stem cell-specific genes and an induction of lineage marker genes. Jmjd1a demethylates H3K9Me2 at the promoter regions of Tcl1, Tcfcp2l1, and Zfp57 and positively regulates the expression of these pluripotency-associated genes
physiological function
JMJD1A forms a homodimer through its catalytic domains, bringing the two active sites close together. Increasing the concentration of JMJD1A facilitates efficient production of unmethylated product from dimethyl-H3K9 and decreases the release of the monomethylated intermediate. Substituting one of the two active sites with an inactive mutant results in a significant reduction of the demethylation rate without changing the affinity to the intermediate. A substrate channeling model is described for the efficient conversion of dimethylated H3K9 into the unmethylated state
physiological function
JMJD1A is increased in most tissues of human fetuses in which oxygen supply is low compared to postnatal levels
physiological function
Jmjd1a is involved in the reversal of H3K9Me2 of bulk chromatin in embryonic stem cells. Jmjd1a demethylates H3K9Me2 at the promoter regions of Tcl1, Tcfcp2l1, and Zfp57 and positively regulates the expression of these pluripotency-associated genes, detailed overview. The embryonic stem cell transcription circuitry is connected to chromatin modulation through H3K9 demethylation in pluripotent cells
physiological function
-
JMJD1A is regulated by hypoxia-inducible factor HIF-2alpha in HepG2 cells under hypoxia. Knockdown or overexpression of JMJD1A can decrease or increase erythropoietin expression, respectively. JMJD1 A can interact with HIF-2alpha to form a coactivator complex, which binds to the hypoxia response elements of erythropoietin and increases erythropoietin expression by catalyzing demethylation of H3K9me2, a transcription suppression marker
physiological function
JMJD1A knockdown in prostate cancer cells antagonizes their proliferation and survival. JMJD1A-dependent genes function in cellular growth, proliferation and survival, JMJD1A enhances c-Myc transcriptional activity by upregulating c-Myc expression levels. JMJD1A activity promotes recruitment of androgen receptor (AR) to the c-Myc gene enhancer and induces H3K9 demethylation, increasing AR-dependent transcription of c-Myc mRNA. JMJD1A regulates c-Myc stability, likely by inhibiting HUWE1. JMJD1A binds to HUWE1, attenuates HUWE1-dependent ubiquitination and subsequent degradation of c-Myc, increasing c-Myc protein levels
physiological function
-
KDM3A facilitates the Xenopus Neurog2 (regulator of neuronal fate specification and differentiation) chromatin accessibility during neuronal transcription. KDM3A is not required for the transition of naive ectoderm to neural progenitor cells but is essential for primary neuron formation. Neurog2 promotes the removal of the repressive H3K9me2 marks and addition of active histone marks, including H3K27ac and H3K4me3, at the NeuroD1 and Tubb2b promoters, the activity depends on the presence of KDM3A
physiological function
KDM3B contains a JmjC domain and is downregulated during differentiation through the recruitment of a corepressor complex. KDM3B displays histone H3K9-me1/2 demethylase activity and induces leukemogenic oncogene lmo2 expression via a synergistic interaction with CBP. KDM3B represses leukemia cell differentiation and is upregulated in blood cells from acute lymphoblastic leukemia-type leukemia patients
physiological function
Kdm3b knockout mice display restricted postnatal growth and female infertility. Kdm3b ablation decreases IGFBP-3 expressed in the kidney by 53% and significantly reduces IGFBP-3 in the blood, which causes an accelerated degradation of IGF-1 and a 36% decrease in circulating IGF-1 concentration. Knockout of Kdm3b in female mice causes irregular estrous cycles, decreases 45% of the ovulation capability and 47% of the fertilization rate, and reduces 44% of the uterine decidual response, which are accompanied with a more than 50% decrease in the circulating levels of the 17beta-estradiol, associated with significantly increased levels of H3K9me1/2/3 in the ovary and uterus
physiological function
KDM4A regulates heterochromatin position-effect variegation, organization of repetitive DNAs, and DNA repair. KDM4A demethylase activity is dispensable for position-effect variegation. KDM4A enzymatic activity is required to relocate heterochromatic double-strand breaks outside the domain, and for organismal survival when DNA repair is compromised. DNA damage triggers KDM4A-dependent changes in the levels of H3K56me3. In heterochromatin, KDM4A loss alters H3K9me3 but not H3K36me3 levels and KDM4A is required for demethylation of H3K56me3 during DNA damage
physiological function
-
knockout of JMJD1B blocks demethylation of H4R3me2s and/or H3K9me2 at distinct clusters of genes and impairs the activation of genes important for hematopoietic stem/progenitor cell differentiation and development. JMJD1B-/- mice show defects in hematopoiesis
physiological function
LSD1 allows transcription factors or corepressor complexes to selectively initiate or repress transcription via demethylation of lysine residues 4 or 9 of histone 3, thereby controlling gene expression programs. LSD1 modulates tumor cell biology by demethylating monomethyl and dimethyl lysines 4 or 9 in histone H3. LSD1 specificity and mechanism of action are complex-dependent. Expression of the chromatin-modifying enzyme lysine-specific demethylase 1 in neuroblastoma is correlated with adverse outcome and inversely correlated with differentiation in neuroblastic tumors
physiological function
LSD1 can act as a transcriptional activator. Androgen receptor and LSD1 form a complex in a ligand-dependent manner and remove the transcriptionally repressive H3K9 methyl groups, thereby de-repressing androgen-receptor-target genes. LSD1 can target different lysine residues and regulate transcription positively or negatively, depending on its binding partners. The large number of LSD1-enriched promoters suggest a broad role in transcriptional regulation for LSD1
physiological function
LSD1 catalyzes the demethylation of mono- and dimethylated histone H3-K4 and also H3-K9, it exhibits diverse transcriptional activities by mediating chromatin reconfiguration. LSD1 represses hTERT transcription via demethylating H3-K4 in normal and cancerous cells, and together with HDACs, participates in the establishment of a stable repression state of the hTERT gene in normal or differentiated malignant cells. Role for LSD1 in controlling hTERT transcription
physiological function
LSD1 is a nuclear amine oxidase that utilizes oxygen as an electron acceptor to reduce methylated lysine to form lysine. It demethylates H3K4m1 and H3K4m2, as well as H3K9m1 and H3K9m2 as a removal of the active methylation mark. LSD1 is associated with co-repressor complexes and promotes suppression or activation of gene expression, e.g. LSD1 might be associated to cooperative recruitment to the NFkappaB p65 site for activation in hyperglycemia
physiological function
LSD1 is a nuclear amine oxidase that utilizes oxygen as an electron acceptor to reduce methylated lysine to form lysine. It demethylates H3K4m1 and H3K4m2, as well as H3K9m1 and H3K9m2 as a removal of the active methylation mark. LSD1 is associated with co-repressor complexes and promotes suppression or activation of gene expression, e.g. LSD1 might be associated to cooperative recruitment to the NFkappaB p65 site for activation in hyperglycemia
physiological function
lysine-specific demethylase 1A (KDM1A/LSD1) is a FAD-dependent enzyme that catalyzes the oxidative demethylation of histone H3K4me1/2 and H3K9me1/2 repressing and activating transcription, respectively
physiological function
overexpression of PHF8 catalyzes the removal of methyl-groups from histone 3 lysine 9 (H3K9) and H4K20, whereas knockdown of the enzyme increases H3K9 methylation. Knockdown of PHF8 also attenuates endothelial proliferation and survival. PHF8 knockdown attenuates the capacity for migration and developing of capillary-like structures. Gene repressor E2F4 is controlled by PHF8. PHF8 maintains E2F4 but not E2F1 expression in endothelial cells and reduces the H3K9me2 level at the E2F4 transcriptional start site
physiological function
PHF8 binds specifically to H3K4me3/2 peptides via an N-terminal PHD finger domain. Knockdown of PHF8 in mouse embryonic carcinoma P19 cells impairs retinoic acid-induced neuronal differentiation, whereas overexpression of PHF8 drives P19 cells toward neuronal differentiation. PHF8 interacts with retinoic acid receptor alpha and functions as a coactivator
physiological function
PHF8 binds to the promoter region of the rDNA gene. Knockdown of PHF8 reduces the expression of rRNA, and overexpression results in upregulation of rRNA transcript. Concomitantly, H3K9me2 levels are elevated in the promoter region of the rDNA gene in PHF8 knockdown cells and significantly reduced upon overexpression of PHF8
physiological function
PHF8 interacts with U1 spliceosomal proteins, such as SRPK1 and snRNP70. The histocompatibility antigen HLA-G is a target of PHF8. The inclusion of HLA-G intron 4, with concomitant RNA Polymerase II accumulation at this intron is controlled by PHF8 and H3K9. Soluble HLA-G is generated after PHF8 knockdown, which leads to reduced T-cell proliferation
physiological function
PHF8 is recruited to promoters by its PHD domain based on interaction with H3K4me2/3 and controls G1-S transition in conjunction with E2F1, HCF-1 and SET1A, at least in part, by removing the repressive H4K20me1 mark from a subset of E2F1-regulated gene promoters. Phosphorylation-dependent PHF8 dismissal from chromatin in prophase is required for the accumulation of H4K20me1 during early mitosis
physiological function
PHF8 over-expression in U2OS but not HeLa cells results in a significant reduction of H3K9me2 level and only a slight reduction of the global level of H4K20me1
physiological function
PHF8 regulates cell survival in the zebrafish developing brain and jaw development. In a model PHF8 regulates zebrafish neuronal cell survival and jaw development in part by directly regulating the expression of the homeodomain transcription factor MSX1/MSXB
physiological function
role of LSD1 in the regulation of gene expression, overview
physiological function
Swm1 and Swm2 (after SWIRM1 and SWIRM2), associate together in a complex. This complex specifically demethylates lysine 9 in histone H3 (H3K9) and both up- and down-regulates expression of different groups of genes. In vitro, bacterially expressed Swm1 also possesses lysine 9 demethylase activity
physiological function
the catalytic activity of lysine-specific demethylase 1 (LSD1) is required for regulation of inflammatory cytokines. LSD1 functions as a transcriptional coregulator through demethylating histone H3 on lysine 4 and lysine 9. Repressive role of LSD1 in proinflammatory cytokine expression such as interleukins IL1alpha, IL1beta, IL6, and IL8 and classical complement components, LSD1 occupies and regulates the promoter of these genes. LSD1 regulates several genes of the complement system in Hep-G2 cells. LSD1 binds directly to the promoter of the IL1beta and IL6 genes
physiological function
-
the enzyme facilitates the Xenopus Neurog2 chromatin accessibility during neuronal transcription. The enzyme is not required for the transition of naive ectoderm to neural progenitor cells but is essential for primary neuron formation
physiological function
the enzyme regulates epidermal homeostasis via direct control of its target genes
physiological function
-
histone H3K9 demethylase JMJD1A modulates hepatic stellate cells activation and liver fibrosis by epigenetically regulating peroxisome proliferator-activated receptor gamma (PPARgamma), molecular mechanism, overview
-
physiological function
-
Swm1 and Swm2 (after SWIRM1 and SWIRM2), associate together in a complex. This complex specifically demethylates lysine 9 in histone H3 (H3K9) and both up- and down-regulates expression of different groups of genes. In vitro, bacterially expressed Swm1 also possesses lysine 9 demethylase activity
-
physiological function
-
Swm1 and Swm2 (after SWIRM1 and SWIRM2), associate together in a complex. This complex specifically demethylates lysine 9 in histone H3 (H3K9) and both up- and down-regulates expression of different groups of genes. In vitro, bacterially expressed Swm1 also possesses lysine 9 demethylase activity
-
physiological function
-
dimethylation of histone H3 lysine 9 (H3K9me2) is a heterochromatic mark linked to DNA methylation and gene repression. Removal of H3K9me2 from gene bodies by the jmjC histone demethylase JMJ25 inhibits DNA methylation and derepresses gene expression. JmjC domain protein JMJ24 antagonizes histone H3K9 demethylase IBM1/JMJ25 function and interacts with RNAi pathways for gene silencing
-
physiological function
-
Kdm3b knockout mice display restricted postnatal growth and female infertility. Kdm3b ablation decreases IGFBP-3 expressed in the kidney by 53% and significantly reduces IGFBP-3 in the blood, which causes an accelerated degradation of IGF-1 and a 36% decrease in circulating IGF-1 concentration. Knockout of Kdm3b in female mice causes irregular estrous cycles, decreases 45% of the ovulation capability and 47% of the fertilization rate, and reduces 44% of the uterine decidual response, which are accompanied with a more than 50% decrease in the circulating levels of the 17beta-estradiol, associated with significantly increased levels of H3K9me1/2/3 in the ovary and uterus
-
physiological function
-
LSD1 is a nuclear amine oxidase that utilizes oxygen as an electron acceptor to reduce methylated lysine to form lysine. It demethylates H3K4m1 and H3K4m2, as well as H3K9m1 and H3K9m2 as a removal of the active methylation mark. LSD1 is associated with co-repressor complexes and promotes suppression or activation of gene expression, e.g. LSD1 might be associated to cooperative recruitment to the NFkappaB p65 site for activation in hyperglycemia
-
additional information
mechanism of histone H3 demethylation by demethylase LSD1, overview
additional information
-
in attached breast epithelial cells, KDM3A expression is maintained at low levels by integrin signaling. Following detachment, integrin signaling is decreased resulting in increased KDM3A expression
additional information
in attached breast epithelial cells, KDM3A expression is maintained at low levels by integrin signaling. Following detachment, integrin signaling is decreased resulting in increased KDM3A expression
additional information
KDM1A likely contains a histone H3 secondary specificity element on the enzyme surface that contributes significantly to its recognition of substrates and products. The active site is too sterically restricted to encompass the minimal H3 21-mer peptide substrate footprint
additional information
although the active site is expanded compared to that of members of the greater amine oxidase superfamily, it is too sterically restricted to encompass the minimal 21-mer peptide substrate footprint. The remainder of the substrate/product is therefore expected to extend along the surface of KDM1A
additional information
transient hyperglycemia induces recruitment of LSD1 to gene regulation sites/promoters. Transient hyperglycemia causes a sustained reduction in both H3K9m2 and H3K9m3 on the NFkappaB-p65 promoter
additional information
transient hyperglycemia induces recruitment of LSD1 to gene regulation sites/promoters. Transient hyperglycemia causes a sustained reduction in both H3K9m2 and H3K9m3 on the NFkappaB-p65 promoter
additional information
-
transient hyperglycemia induces recruitment of LSD1 to gene regulation sites/promoters. Transient hyperglycemia causes a sustained reduction in both H3K9m2 and H3K9m3 on the NFkappaB-p65 promoter
-
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UNIPROT
ENTRY NAME
ORGANISM
NO. OF AA
NO. OF TRANSM. HELICES
MOLECULAR WEIGHT[Da]
SOURCE
SEQUENCE
LOCALIZATION PREDICTION
The reliability class of the localization prediction ranges from 1 (very reliable) to 5 (not reliable).
The reliability class of the localization prediction ranges from 1 (very reliable) to 5 (not reliable). PHF8_DANRE
1032
0
114222
Swiss-Prot
other Location (Reliability: 2)
PHF8_HUMAN
1060
0
117864
Swiss-Prot
Mitochondrion (Reliability: 2)
PHF8_MOUSE
1023
0
113553
Swiss-Prot
other Location (Reliability: 3)
HAIR_HUMAN
1189
0
127495
Swiss-Prot
other Location (Reliability: 1)
HAIR_MOUSE
1182
0
127193
Swiss-Prot
other Location (Reliability: 1)
HAIR_RAT
1181
0
127307
Swiss-Prot
other Location (Reliability: 1)
KDM3A_CHICK
1325
0
149333
Swiss-Prot
other Location (Reliability: 4)
KDM3A_HUMAN
1321
0
147341
Swiss-Prot
other Location (Reliability: 4)
KDM3A_MOUSE
1323
0
147847
Swiss-Prot
other Location (Reliability: 3)
KDM3A_RAT
1214
0
135404
Swiss-Prot
other Location (Reliability: 3)
KDM3B_HUMAN
1761
0
191581
Swiss-Prot
Secretory Pathway (Reliability: 5)
KDM3B_MOUSE
1562
0
170875
Swiss-Prot
other Location (Reliability: 4)
KD3AA_XENLA
1331
0
149611
Swiss-Prot
other Location (Reliability: 2)
KD3AB_XENLA
1334
0
149945
Swiss-Prot
other Location (Reliability: 2)
A0A6J8CLP1_MYTCO
734
0
83457
TrEMBL
other Location (Reliability: 1)
A0A6J8B024_MYTCO
2458
0
277577
TrEMBL
Mitochondrion (Reliability: 2)
A0A6J8CMN8_MYTCO
808
0
92203
TrEMBL
other Location (Reliability: 1)
KDM1A_HUMAN
852
0
92903
Swiss-Prot
Secretory Pathway (Reliability: 5)
LSD2_SCHPO
Schizosaccharomyces pombe (strain 972 / ATCC 24843)
1273
0
142490
Swiss-Prot
-
KDM1A_MOUSE
853
0
92851
Swiss-Prot
Secretory Pathway (Reliability: 4)
KDM4A_DROME
495
0
56990
Swiss-Prot
other Location (Reliability: 2)
LSD1_SCHPO
Schizosaccharomyces pombe (strain 972 / ATCC 24843)
1000
0
112829
Swiss-Prot
-
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PDB
SCOP
CATH
UNIPROT
ORGANISM
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MOLECULAR WEIGHT
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
300000
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SUBUNIT
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
additional information
additional information
-
the PHD domain adjacent to the catalytic domain in PHF8 may recognize methyl H3K9 and contribute to its demethylation. PHF8 consists of 16 alpha-helices and 12 beta-strands, arranged in a similar manner to a known JmjC-domain-containing histone demethylase, JHDM1a. In the presence of Fe2+ and 2-oxoglutarate, Fe2+ sits in the center of the c-PHF8 catalytic core, which consists of nine hydrophobic residues
additional information
from N- to C-terminus, KDM1A is composed of an unstructured region that contains the nuclear localization signal and three structured domains: a SWI3p, Rsc8p, and Moira (SWIRM) domain, an amine oxidase domain (AOD), and an unprecedented intervening domain within the AOD colloquially known as the tower. The tower domain of KDM1A is composed of two antiparallel alpha-helices (termed TalphaA and TalphaB) that form a coiled coil and extend approximately 100 A from the AOD
additional information
-
the major functional domains of enzyme HR include a single zinc finger domain, multiple LXXLL motifs that mediate protein-protein interactions, and a JmjC domain in its C-terminus
additional information
the major functional domains of enzyme HR include a single zinc finger domain, multiple LXXLL motifs that mediate protein-protein interactions, and a JmjC domain in its C-terminus
additional information
from N- to C-terminus, KDM1A is composed of an unstructured region that contains the nuclear localization signal and three structured domains: a SWI3p, Rsc8p, and Moira (SWIRM) domain, an amine oxidase domain (AOD), and an unprecedented intervening domain within the AOD colloquially known as the tower. The tower domain of KDM1A is composed of two antiparallel alpha-helices (termed TalphaA and TbetaB) that form a coiled coil and extend approximately 100 A from the amine oxidase domain (AOD)
additional information
-
two active sites of a JMJD1A dimer are required for effective demethylation
additional information
two active sites of a JMJD1A dimer are required for effective demethylation
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CRYSTALLIZATION (Commentary)
ORGANISM
UNIPROT
LITERATURE
P