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Information on EC 1.14.11.65 - [histone H3]-dimethyl-L-lysine9 demethylase and Organism(s) Homo sapiens and UniProt Accession Q9Y4C1
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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
- dermal
-
stratum
- corneum
-
permeation
-
uvb-induced
-
transdermal
- keratinocytes
- collagen
- carcinogenesis
-
percutaneous
- follicle
- notch
- erythema
-
solar
-
wrinkle
-
photoaging
-
transepidermal
- guinea
- hyperplasia
-
photocarcinogenesis
-
irritation
- flap
- dermatitis
-
iontophoresis
-
photodamage
- alopecia
- scalp
-
uvb-irradiated
-
photoprotective
- propylene
-
cream
-
full-thickness
-
sunscreen
- sunburn
-
tape
-
franz
- demethylases
-
sebaceous
-
ointment
-
cyclobutane
- dorsum
-
bald
- 8-methoxypsoralen
-
intracutaneous
- nevus
-
microneedle
-
ultraviolet-induced
-
eyebrow
- tranylcypromine
-
sencar
- medicine
- drug development
The taxonomic range for the selected organisms is: Homo sapiens
The enzyme appears in selected viruses and cellular organisms
The enzyme appears in selected viruses and cellular organisms
Reaction Schemes
hide(Overall reactions are displayed. Show all >>)
Synonyms
hairless, kdm1a, kdm7a, lysine specific demethylase 1, lysine-specific demethylase-1, lysine-specific histone demethylase 1, hairless protein, kiaa1718, jmj27, lysine-specific demethylase 1a, 
more
topSYNONYM 
ORGANISM
UNIPROT
COMMENTARY 
LITERATURE
BHC110
histone demethylase
histone H3K9 demethylase
JMJD1A
LSD1
lysine-specific demethylase 1
PHF8
additional information
LSD1
-
lysine-specific demethylase 1
-
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.
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-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,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
-
-
-
?
[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-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-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-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-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-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
-
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-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-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-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-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
?
-
-
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
?
-
JMJD1A epigenetically modifies H3K9me2 in the PPARgamma gene locus
-
-
?
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
?
-
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
?
-
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
-
-
-
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-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,N6-dimethyl-L-lysine 9 + 2-oxoglutarate + O2
[histone H3]-N6-methyl-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,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-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-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-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 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-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-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-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-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
?
-
-
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
?
-
JMJD1A epigenetically modifies H3K9me2 in the PPARgamma gene locus
-
-
?
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
?
-
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
?
-
-
no activity with [histone H3]-N6,N6,N6-trimethyl-L-lysine9
-
-
-
additional information
?
-
no activity with [histone H3]-N6,N6,N6-trimethyl-L-lysine9
-
-
-
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)
METALS and IONS
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
Fe2+
Fe2+
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
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
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
(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
-
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
-
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
-
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
-
histone H3
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
-
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
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
additional information
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
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
-
additional information
demethylation activity is decreased by other modifications on the H3 tail, such as acetylation and phosphorylation, suggesting possible regulatory mechanisms
-
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
KDM1A tolerance for 3-[(3-cholamidopropyl)-dimethylammonio]-1-propanesulfonate (CHAPS) at 0.01% w/v and dimethyl sulfoxide (DMSO) at 10% v/v
-
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
small molecule inhibitors of LSD1 inhibit xenograft tumor growth
-
ACTIVATING COMPOUND
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
fisetin
fisetin induces DNA damage via critical transcription factor RFXAP/KDM4A-dependent histone H3K36 demethylation, thus causing inhibition of proliferation in pancreatic adenocarcinoma (PDAC). Fisetin inhibits cell proliferation and induces DNA damage and S-phase arrest in PDAC. Expression of RFXAP and other DNA-damage response genes is upregulated by fisetin. RFXAP targets KDM4A. Overexpression of RFXAP upregulates KDM4A and attenuates methylation of H3K36, impairing DNA repair and enhancing the DNA damage induced by fisetin
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
-
KM VALUE [mM]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
TURNOVER NUMBER [1/s]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
kcat/KM VALUE [1/mMs-1]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
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
-
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
pH OPTIMUM
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
7.5
TEMPERATURE OPTIMUM
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
37
ORGANISM
COMMENTARY
LITERATURE
UNIPROT
SEQUENCE DB
SOURCE
-
UniProt
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
SOURCE TISSUE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
SOURCE
enzyme JMJD1C is upregulated in patient esophageal cancer tissues and different esophageal cancer cell lines
during the differentiation of leukemic HL60 cells, the decreased hTERT expression is accompanied by the LSD1 recruitment to the hTERT promoter
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lysine-specific demethylase 1 colocalizes with androgen receptor
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lysine-specific demethylase 1 colocalizes with androgen receptor
additional information
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
nuclear extracts of HeLa cells contain LSD1 that is associated with folate
lysine-specific demethylase 1 is strongly expressed in poorly differentiated neuroblastoma
additional information
mRNA expression is increased in most tissues of human fetuses in whom oxygen supply is low compared to postnatal levels
additional information
-
immunohistochemic analysis of tissue localization, overview
additional information
immunohistochemic analysis of tissue localization, overview
LOCALIZATION
ORGANISM
UNIPROT
COMMENTARY
GeneOntology No.
LITERATURE
SOURCE
shift of cytoplasmic JMJD1A into the nucleus on hypoxia treatment
enzyme LSD1 is present at the proximal region of the microsomal PGES-1 promoter
-
LSD1 is present on chromatin in both the presence and the absence of estrogens
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GENERAL INFORMATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
malfunction
metabolism
JMJD1A as an epigenetic regulator that modulates hepatic stellate cell activation and liver fibrosis through targeting PPARgamma gene expression, molecular mechanism, overview
physiological function
evolution
malfunction
metabolism
physiological function
additional information
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
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
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
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
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 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
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 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
histone H3 lysine 9 demethylase enzymes, KDM3A and KDM4B, EC 1.14.11.66, cooperate to regulate ER activity via an autoregulatory loop that facilitates the recruitment of each coactivating enzyme to chromatin. KDM3A primes chromatin for deposition of the ER pioneer factor FOXA1 and recruitment of the ER-transcriptional complex, all prior to ER recruitment. A KDM3A/KDM4B/FOXA1 coregulated gene signature is enriched for proproliferative and ER-target gene sets. Depletion of both KDM3A and KDM4B has a greater inhibitory effect on ER activity and cell growth than knockdown of each individual enzyme
physiological function
KDM3A is a positive regulator for hippo target genes. KDM3A promotes gene expression through upregulation of YAP1 expression, and through facilitating H3K27ac on the enhancers of hippo target genes. KDM3A depletion causes H3K9me2 upregulation mainly on TEAD1-binding enhancers rather than gene bodies, further resulting in H3K27ac decrease, less TEAD1 binding on enhancers and impaired transcription. KDM3A is associated with p300 and required for p300 recruitment to enhancers. KDM3A deficiency delays cancer cell growth and migration, which is rescued by YAP1 expression. KDM3A expression is correlated with YAP1 and hippo target genes in colorectal cancer patient tissues
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
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
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 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
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
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
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
switching off the enzyme in cancer cells increases their ability to move around the body
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
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
physiological function
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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-oxoguanineDNA glycosylase 1 and topoisomerase IIb, triggering chromatin and DNA conformational changes that are essential for estrogen-induced transcription
physiological function
methylation on the N-terminal tails of histone lysines serves as an epigenetic control mechanism, which is regulated by demathylases
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
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
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
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
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
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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
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
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
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
role of LSD1 in the regulation of gene expression, overview
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 regulates epidermal homeostasis via direct control of its target genes
physiological function
catalyzes the demethylation of di- and trimethylated Lys9 (reactions of EC 1.14.11.65 and 1.14.11.66) and Lys36 in histone H3 (reactions of EC 1.14.11.27 and 1.14.11.69). Jmjd2a responds to 5-hydroxytryptamine and promotes the expression of the brain-derived neurotrophic factor (Bdnf), a protein critically involved in neuropathic pain. JMJD2A binds to the promoter of Bdnf and demethylates H3K9me3 and H3K36me3 at the Bdnf promoter to promote the expression of Bdnf
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
mechanism of histone H3 demethylation by demethylase LSD1, overview
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
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). KDM3A_HUMAN
1321
0
147341
Swiss-Prot
other Location (Reliability: 4)
MOLECULAR WEIGHT
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
300000
SUBUNIT
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
additional information
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
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)
CRYSTALLIZATION (Commentary)
ORGANISM
UNIPROT
LITERATURE
purified recombinant truncated enzyme LSD1 comprising residues 172-833 in complex with recombinant human CoREST residues 308-440, and peptide inhibitors 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, N2-L-seryl-L-arginyl-L-threonyl-L-methionyl-L-glutaminyl-L-threonyl-L-alanyl-L-arginyl-L-lysyl-L-seryl-L-threonylglycylglycyl-L-lysyl-L-alanyl-L-prolyl-L-arginyl-L-lysyl-L-glutaminyl-L-leucyl-(N6-(L-seryl))-L-lysine-amide, and L-homoseryseryl-L-arginyl-L-threonyl-L-methionyl-L-glutaminyl-L-threonyl-L-alanyl-L-arginyl-L-lysyl-L-seryl-L-threonylglycylglycyl-L-lysyl-L-alanyl-L-prolyl-L-arginyl-L-lysyl-L-glutaminyl-L-leucyl-(N6-(L-homoseryl))-L-lysine, by hanging drop vapor diffusion method, mixing of 0.001 ml of 9 mg/ml protein solution with 0.001 ml of reservoir solution containing 100 mM N-(carbamoylmethyl)iminodiacetic acid, pH 5.5, and 1.18-1.28M potassium sodium tartrate tetrahydrate, 20°C, crystals are soaked in a solution containing 100 mM N-(carbamoylmethyl) iminodiacetic acid buffer, pH 5.5, with 1.14 M potassium sodium tartrate tetrahydrate, 10% glycerol, and 2 mM LSD1 inhibitor peptide for 2 h, X-ray diffraction structure determination and analysis at 2.53-2.69 A resolution
recombinant GST-tagged enzyme fragment in complex with inhibitor tranylcypromine, X-ray diffraction structure determination and analysis at 2.25 A resolution
PROTEIN VARIANTS
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
D1012N
F279S
V1056M
additional information
D1012N
site-directed mutagenesis, reduced activity of the mutant compared to wild-type
D1012N
mutation identified in patients with atrichia with papular lesions, almost abolishes the demethylase activity
F279S
mutation identified in patients with X-linked mental retardation. abolishes catalytic activity
F279S
mutation identified in X-linked mental retardation patients, mutant is defective in enzymatic activity
V1056M
site-directed mutagenesis, reduced activity of the mutant compared to wild-type
V1056M
mutation identified in patients with atrichia with papular lesions, almost abolishes the demethylase activity
additional information
-
RNAi-mediated knockdown of KDM3A, Kdm3a knockdown 4T07 cells
additional information
RNAi-mediated knockdown of KDM3A, Kdm3a knockdown 4T07 cells
additional information
down-regulation of the expression of JMJD1A using small interfering or short hairpin RNAs
additional information
-
LSD1 knockdown by siRNA inhibits 8-oxo-guanine production
additional information
-
ectopic expression of HR in HEK-293 cells leads to either upregulation or downregulation of the majority of the HR target genes, overview. HR overexpression can lead to H3K9 demethylation in the target gene promoters or transcription regulatory elements, TREs, enzyme overexpression leads to a partial demethylation of H3K9 within the TREs of Mxi1 and Caspase14
additional information
ectopic expression of HR in HEK-293 cells leads to either upregulation or downregulation of the majority of the HR target genes, overview. HR overexpression can lead to H3K9 demethylation in the target gene promoters or transcription regulatory elements, TREs, enzyme overexpression leads to a partial demethylation of H3K9 within the TREs of Mxi1 and Caspase14
additional information
enzyme knockdown by expression of specific sh-RNAs targeting PHF8 in HEK 293 T cells
additional information
knockdown of JMJD1C in esophageal cancer cell lines, generation of Eca-109 and EC-18 EC cells that stably express JMJD1C shRNA
additional information
-
knockdown of JMJD1C in esophageal cancer cell lines, generation of Eca-109 and EC-18 EC cells that stably express JMJD1C shRNA
additional information
the enzyme is knocked out by expression of specific siRNA for LSD1 in chondrocytes
additional information
construction of an enzyme mutant with a deletion of the NH2-terminal 184 amino acid residues (DELTA184 LSD1)
additional information
knockdown or knockout of PHF8 in 293T cells by RNAi or CRISPR-Cas9 system. The small guide RNAs (sgRNAs) target exon 8, which encodes amino acids 262-315 of the JmjC domain, and abolish PHF8 expression
additional information
knockdown or knockout of PHF8 in 293T cells by RNAi or CRISPR-Cas9 system. The small guide RNAs (sgRNAs) target exon 8, which encodes amino acids 262-315 of the JmjC domain, and abolish PHF8 expression
additional information
LSD1 knockdown by transient siRNA transfection in HCT-116 cells
additional information
MDA-MB231 cells are transiently transfected with three different siRNA directed against LSD1 causing significant knockdown of LSD1 in all samples on both mRNA and protein level. LSD1 knockdown leads to significant induction of the steady state transcript levels of interleukin 1alpha, 1beta, 6 and 8 genes. Interleukin 1beta protein levels are significantly enhanced in the supernatant of the cells after LSD1 knockdown
additional information
small interference RNA-mediated depletion of both LSD1
PURIFICATION (Commentary)
ORGANISM
UNIPROT
LITERATURE
recombinant full-length His6-tagged LSD1 from Escherichia coli strain BL21(DE3) by nickel affinity chromatography and dialysis
recombinant N-terminally His-tagged enzyme by nickel affinity chromatography from Escherichia coli BL21(DE3), or by ammonium sulfate fractionation and anion exchange chromatography, recombinant N-terminally truncated GST-tagged LSD1 by glutathione affinity chromatography
Streptactin-Sepharose column chromatography and FLAG M2-agarose column chromatography
CLONED (Commentary)
ORGANISM
UNIPROT
LITERATURE
gene KDM3A, quantitative RT-PCR enzyme expression analysis, recombinant expression of wild-type KDM3A or catalytically inactive KDM3A mutant [KDM3A(H1120G/D1122N)] in MCF-10A cells
gene HR, real-time RT-PCR enzyme expression analysis, ectopic expression of wild-type protein hairless, HR, but not JmjC-mutant HR, leads to pronounced demethylation of H3K9 in cultured human HeLa cells, reombinant expression of Flag-tagged HR in HEK-293 cells
gene KDM1A, codon optimized, recombinant expression of the enzyme LSD1, residues 151-852, in Escherichia coli
gene KDM1A, recombinant expression of full-length His6-tagged human LSD1 from pET15b bacterial expression vector in Escherichia coli strain BL21(DE3)
gene KDM1A, recombinant expression of N-terminally His-tagged full-length LSD1 protein and deletion mutant DELTA184 LSD1lacking the N-terminal 184 amino acid residues
gene lsd1, real-time reverse transcription-PCR expression enzyme analysis
gene lsd1, recombinant expression of GST-tagged enzyme fragment consisting of residues 172-833 in Escherichia coli
recombinant expression of N-terminally His-tagged enzyme in Escherichia coli BL21(DE3), recombinant expression of N-terminally truncated GST-tagged LSD1
EXPRESSION
ORGANISM
UNIPROT
LITERATURE
expression is reliably upregulated in various cells in response to hypoxia and by desferroxamine treatment
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. Expression of either EGFR or MEK2DD decreases the levels of KDM3A in detached MCF10A cells
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. KDM3A protein levels are increased in attached MCF-10A cells treated with the EGFR inhibitor gefitinib. Detachment and loss of integrin and growth factor receptor signaling induces KDM3A expression
upregulation of JMJD1A mRNA and protein in cultured human cells exposed to hypoxia or iron scavengers in vitro is abrogated when hypoxia-inducible factor-1 (HIF-1) signaling is blocked by siRNA. A single pivotal hypoxia responsive element in the promoter of the human JMJD1A gene mediates JMJD1A upregulation by hypoxia, iron scavengers, and HIF-1
differentiation of neuroblastoma cells results in down-regulation of LSD1
JMJD1A gene expression is upregulated by beta-adrenergic agonists, and by hypoxia-inducible factor 1alpha (HIF1alpha), hypoxia, starvation and iron scavengers in tumor tissues
treatment by hypoxia (1% O2, 6 days) but not by androgen deprivation or interleukin-6, leads to posttranscriptional upregulation of PHF8 in LNCaP cells
APPLICATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
medicine
drug development
the enzyme is a target for development of more potent JMJD1A/MALAT1 inhibitors for the prevention of tumor metastasis
medicine
additional information
LSD1 is a rational target for inducing the reexpression of aberrantly silenced genes
medicine
KDM3A expression in human breast cancer cell lines and tumors is defective
medicine
KDM3A deficiency delays cancer cell growth and migration, which is rescued by YAP1 expression. KDM3A expression is correlated with YAP1 and hippo target genes in colorectal cancer patient tissues
medicine
KDM3B represses leukemia cell differentiation and is upregulated in blood cells from acute lymphoblastic leukemia-type leukemia patients
medicine
fisetin induces DNA damage via critical transcription factor RFXAP/KDM4A-dependent histone H3K36 demethylation, thus causing inhibition of proliferation in pancreatic adenocarcinoma (PDAC). Fisetin inhibits cell proliferation and induces DNA damage and S-phase arrest in PDAC. Expression of RFXAP and other DNA-damage response genes is upregulated by fisetin. RFXAP expression is relatively low in PDAC and correlates with tumor stage and poor prognosis. Fisetin enhances the effect of chemotherapy on pancreatic cancer cells
medicine
JMJD2A overexpression increases the mRNA and protein level of brain-derived neurotrophic factor Bdnf, a protein critically involved in neuropathic pain. JMJD2A binds to the promoter of Bdnf and demethylates H3K9me3 and H3K36me3 at the Bdnf promoter to promote the expression of Bdnf
REF.
AUTHORS
TITLE
JOURNAL
VOL.
PAGES
YEAR
ORGANISM (UNIPROT)
PUBMED ID
SOURCE
Metzger, E.; Wissmann, M.; Yin, N.; Muller, J.M.; Schneider, R.; Peters, A.H.; Gunther, T.; Buettner, R.; Schule, R.
LSD1 demethylates repressive histone marks to promote androgen-receptor-dependent transcription
Nature
437
436-439
2005
Homo sapiens
Wellmann, S.; Bettkober, M.; Zelmer, A.; Seeger, K.; Faigle, M.; Eltzschig, H.K.; Buehrer, C.
Hypoxia upregulates the histone demethylase JMJD1A via HIF-1
Biochem. Biophys. Res. Commun.
372
892-897
2008
Rattus norvegicus (Q63679), Homo sapiens (Q9Y4C1)
Perillo, B.; Ombra, M.; Bertoni, A.; Cuozzo, C.; Sacchetti, S.; Sasso, A.; Chiariotti, L.; Malorni, A.; Abbondanza, C.; Avvedimento, E.
DNA oxidation as triggered by H3K9me2 demethylation drives estrogen-induced gene expression
Science
319
202-206
2008
Homo sapiens
Suganuma, T.; Workman, J.
Features of the PHF8/KIAA1718 histone demethylase
Cell Res.
20
861-862
2010
Homo sapiens
Cai, Y.; Fu, X.; Deng, Y.
Histone demethylase JMJD1C regulates esophageal cancer proliferation Via YAP1 signaling
Am. J. Cancer Res.
7
115-124
2017
Homo sapiens (Q15652), Homo sapiens
El Mansouri, F.; Nebbaki, S.; Kapoor, M.; Afif, H.; Martel-Pelletier, J.; Pelletier, J.; Benderdour, M.; Fahmi, H.
Lysine-specific demethylase 1-mediated demethylation of histone H3 lysine 9 contributes to interleukin 1beta-induced microsomal prostaglandin E synthase 1 expression in human osteoarthritic chondrocytes
Arthritis Res. Ther.
16
R113
2014
Homo sapiens (O60341)
Shen, Y.; Pan, X.; Zhao, H.
The histone demethylase PHF8 is an oncogenic protein in human non-small cell lung cancer
Biochem. Biophys. Res. Commun.
451
119-125
2014
Homo sapiens (Q9UPP1)
Choi, J.Y.; Jo, S.A.
KDM7A histone demethylase mediates TNF-alpha-induced ICAM1 protein upregulation by modulating lysosomal activity
Biochem. Biophys. Res. Commun.
478
1355-1362
2016
Homo sapiens (Q6ZMT4), Homo sapiens
Burg, J.M.; Gonzalez, J.J.; Maksimchuk, K.R.; McCafferty, D.G.
Lysine-specific demethylase 1A (KDM1A/LSD1) product recognition and kinetic analysis of full-length histones
Biochemistry
55
1652-1662
2016
Homo sapiens (O60341)
Maina, P.K.; Shao, P.; Jia, X.; Liu, Q.; Umesalma, S.; Marin, M.; Long, D.; Concepcion-Roman, S.; Qi, H.H.
Histone demethylase PHF8 regulates hypoxia signaling through HIF1alpha and H3K4me3
Biochim. Biophys. Acta
1860
1002-1012
2017
Homo sapiens (Q9UPP1), Homo sapiens (Q9Y4C1)
Amano, Y.; Kikuchi, M.; Sato, S.; Yokoyama, S.; Umehara, T.; Umezawa, N.; Higuchi, T.
Development and crystallographic evaluation of histone H3 peptide with N-terminal serine substitution as a potent inhibitor of lysine-specific demethylase 1
Bioorg. Med. Chem.
25
2617-2624
2017
Homo sapiens (O60341)
Pedanou, V.E.; Gobeil, S.; Tabaries, S.; Simone, T.M.; Zhu, L.J.; Siegel, P.M.; Green, M.R.
The histone H3K9 demethylase KDM3A promotes anoikis by transcriptionally activating pro-apoptotic genes BNIP3 and BNIP3L
eLife
5
e16844
2016
Homo sapiens, Homo sapiens (Q9Y4C1)
Liu, L.; Kim, H.; Casta, A.; Kobayashi, Y.; Shapiro, L.; Christiano, A.
Hairless is a histone H3K9 demethylase
FASEB J.
28
1534-1542
2014
Homo sapiens, Homo sapiens (O43593)
Jiang, Y.; Wang, S.; Zhao, Y.; Lin, C.; Zhong, F.; Jin, L.; He, F.; Wang, H.
Histone H3K9 demethylase JMJD1A modulates hepatic stellate cells activation and liver fibrosis by epigenetically regulating peroxisome proliferator-activated receptor gamma
FASEB J.
29
1830-1841
2015
Rattus norvegicus (Q63679), Homo sapiens (Q9Y4C1), Rattus norvegicus Sprague-Dawley (Q63679)
Liu, Y.W.; Xia, R.; Lu, K.; Xie, M.; Yang, F.; Sun, M.; De, W.; Wang, C.; Ji, G.
LincRNAFEZF1-AS1 represses p21 expression to promote gastric cancer proliferation through LSD1-mediated H3K4me2 demethylation
Mol. Cancer
16
39
2017
Homo sapiens (O60341)
Tee, A.E.; Ling, D.; Nelson, C.; Atmadibrata, B.; Dinger, M.E.; Xu, N.; Mizukami, T.; Liu, P.Y.; Liu, B.; Cheung, B.; Pasquier, E.; Haber, M.; Norris, M.D.; Suzuki, T.; Marshall, G.M.; Liu, T.
The histone demethylase JMJD1A induces cell migration and invasion by up-regulating the expression of the long noncoding RNA MALAT1
Oncotarget
5
1793-1804
2014
Homo sapiens (D6W5M4)
Gu, L.; Hitzel, J.; Moll, F.; Kruse, C.; Malik, R.A.; Preussner, J.; Looso, M.; Leisegang, M.S.; Steinhilber, D.; Brandes, R.P.; Fork, C.
The histone demethylase PHF8 is essential for endothelial cell migration
PLoS ONE
11
e0146645
2016
Homo sapiens (Q9UPP1)
Xiao, C.; Liu, Y.; Xie, C.; Tu, W.; Xia, Y.; Costa, M.; Zhou, X.
Cadmium induces histone H3 lysine methylation by inhibiting histone demethylase activity
Toxicol. Sci.
145
80-89
2015
Homo sapiens (Q9Y4C1)
Mimasu, S.; Sengoku, T.; Fukuzawa, S.; Umehara, T.; Yokoyama, S.
Crystal structure of histone demethylase LSD1 and tranylcypromine at 2.25 A
Biochem. Biophys. Res. Commun.
366
15-22
2008
Homo sapiens (O60341)
Wellmann, S.; Bettkober, M.; Zelmer, A.; Seeger, K.; Faigle, M.; Eltzschig, H.K.; Buehrer, C.
Hypoxia upregulates the histone demethylase JMJD1A via HIF-1
Biochem. Biophys. Res. Commun.
372
892-897
2008
Homo sapiens (Q9Y4C1)
Janzer, A.; Lim, S.; Fronhoffs, F.; Niazy, N.; Buettner, R.; Kirfel, J.
Lysine-specific demethylase 1 (LSD1) and histone deacetylase 1 (HDAC1) synergistically repress proinflammatory cytokines and classical complement pathway components
Biochem. Biophys. Res. Commun.
421
665-670
2012
Homo sapiens (O60341)
Gaweska, H.; Henderson Pozzi, M.; Schmidt, D.M.; McCafferty, D.G.; Fitzpatrick, P.F.
Use of pH and kinetic isotope effects to establish chemistry as rate-limiting in oxidation of a peptide substrate by LSD1
Biochemistry
48
5440-5445
2009
Homo sapiens (O60341)
Luka, Z.; Moss, F.; Loukachevitch, L.V.; Bornhop, D.J.; Wagner, C.
Histone demethylase LSD1 is a folate-binding protein
Biochemistry
50
4750-4756
2011
Homo sapiens (O60341)
Schulte, J.H.; Lim, S.; Schramm, A.; Friedrichs, N.; Koster, J.; Versteeg, R.; Ora, I.; Pajtler, K.; Klein-Hitpass, L.; Kuhfittig-Kulle, S.; Metzger, E.; Schuele, R.; Eggert, A.; Buettner, R.; Kirfel, J.
Lysine-specific demethylase 1 is strongly expressed in poorly differentiated neuroblastoma implications for therapy
Cancer Res.
69
2065-2071
2009
Homo sapiens (O60341)
Yamane, K.; Toumazou, C.; Tsukada, Y.; Erdjument-Bromage, H.; Tempst, P.; Wong, J.; Zhang, Y.
JHDM2A, a JmjC-containing H3K9 demethylase, facilitates transcription activation by androgen receptor
Cell
125
483-95
2006
Homo sapiens (Q9Y4C1)
Zhu, Z.; Wang, Y.; Li, X.; Wang, Y.; Xu, L.; Wang, X.; Sun, T.; Dong, X.; Chen, L.; Mao, H.; Yu, Y.; Li, J.; Chen, P.; Chen, C.
PHF8 is a histone H3K9me2 demethylase regulating rRNA synthesis
Cell Res.
20
794-801
2010
Homo sapiens (Q9UPP1)
Qiu, J.; Shi, G.; Jia, Y.; Li, J.; Wu, M.; Li, J.; Dong, S.; Wong, J.
The X-linked mental retardation gene PHF8 is a histone demethylase involved in neuronal differentiation
Cell Res.
20
908-18
2010
Homo sapiens (Q9UPP1)
Sar, A.; Ponjevic, D.; Nguyen, M.; Box, A.H.; Demetrick, D.J.
Identification and characterization of demethylase JMJD1A as a gene upregulated in the human cellular response to hypoxia
Cell Tissue Res.
337
223-234
2009
Homo sapiens (Q9Y4C1)
Huang, Y.; Stewart, T.M.; Wu, Y.; Baylin, S.B.; Marton, L.J.; Perkins, B.; Jones, R.J.; Woster, P.M.; Casero, R.A.
Novel oligoamine analogues inhibit lysine-specific demethylase 1 and induce reexpression of epigenetically silenced genes
Clin. Cancer Res.
15
7217-7228
2009
Homo sapiens (O60341)
Brasacchio, D.; Okabe, J.; Tikellis, C.; Balcerczyk, A.; George, P.; Baker, E.K.; Calkin, A.C.; Brownlee, M.; Cooper, M.E.; El-Osta, A.
Hyperglycemia induces a dynamic cooperativity of histone methylase and demethylase enzymes associated with gene-activating epigenetic marks that coexist on the lysine tail
Diabetes
58
1229-1236
2009
Homo sapiens (O60341), Mus musculus (Q6ZQ88), Mus musculus C57BL/6 (Q6ZQ88)
Leisegang, M.; Gu, L.; Preussner, J.; Guenther, S.; Hitzel, J.; Ratiu, C.; Weigert, A.; Chen, W.; Schwarz, E.; Looso, M.; Fork, C.; Brandes, R.
The histone demethylase PHF8 facilitates alternative splicing of the histocompatibility antigen HLA-G
FEBS Lett.
593
487-498
2019
Homo sapiens (Q9UPP1)
Tian, Z.; Yao, L.; Shen, Y.; Guo, X.; Duan, X.
Histone H3K9 demethylase JMJD1A is a co-activator of erythropoietin expression under hypoxia
Int. J. Biochem. Cell Biol.
109
33-39
2019
Homo sapiens
Goda, S.; Isagawa, T.; Chikaoka, Y.; Kawamura, T.; Aburatani, H.
Control of histone H3 lysine 9 (H3K9) methylation state via cooperative two-step demethylation by jumonji domain containing 1A (JMJD1A) homodimer
J. Biol. Chem.
288
36948-36956
2013
Homo sapiens, Homo sapiens (Q9Y4C1)
Kim, J.; Kim, K.; Eom, G.; Choe, N.; Kee, H.; Son, H.; Oh, S.; Kim, D.; Pak, J.; Baek, H.; Kook, H.; Hahn, Y.; Kook, H.; Chakravarti, D.; Seo, S.
KDM3B is the H3K9 demethylase involved in transcriptional activation of lmo2 in leukemia
Mol. Cell. Biol.
32
2917-2933
2012
Homo sapiens (Q7LBC6)
Liang, Y.; Vogel, J.; Narayanan, A.; Peng, H.; Kristie, T.
Inhibition of the histone demethylase LSD1 blocks alpha-herpesvirus lytic replication and reactivation from latency
Nat. Med.
15
1312-1317
2009
Homo sapiens (O60341)
Qi, H.; Sarkissian, M.; Hu, G.; Wang, Z.; Bhattacharjee, A.; Gordon, D.; Gonzales, M.; Lan, F.; Ongusaha, P.; Huarte, M.; Yaghi, N.; Lim, H.; Garcia, B.; Brizuela, L.; Zhao, K.; Roberts, T.; Shi, Y.
Histone H4K20/H3K9 demethylase PHF8 regulates zebrafish brain and craniofacial development
Nature
466
503-507
2010
Danio rerio (P0CH95), Homo sapiens (Q9UPP1)
Liu, W.; Tanasa, B.; Tyurina, O.; Zhou, T.; Gassmann, R.; Liu, W.; Ohgi, K.; Benner, C.; Garcia-Bassets, I.; Aggarwal, A.; Desai, A.; Dorrestein, P.; Glass, C.; Rosenfeld, M.
PHF8 mediates histone H4 lysine 20 demethylation events involved in cell cycle progression
Nature
466
508-512
2010
Homo sapiens (Q9UPP1)
Fan, L.; Peng, G.; Sahgal, N.; Fazli, L.; Gleave, M.; Zhang, Y.; Hussain, A.; Qi, J.
Regulation of c-Myc expression by the histone demethylase JMJD1A is essential for prostate cancer cell growth and survival
Oncogene
35
2441-2452
2015
Homo sapiens (Q9Y4C1)
Zhu, Q.; Liu, C.; Ge, Z.; Fang, X.; Zhang, X.; Straat, K.; Bjoerkholm, M.; Xu, D.
Lysine-specific demethylase 1 (LSD1) is required for the transcriptional repression of the telomerase reverse transcriptase (hTERT) gene
PLoS ONE
3
e1446
2008
Homo sapiens (O60341)
Huang, Y.; Greene, E.; Murray Stewart, T.; Goodwin, A.C.; Baylin, S.B.; Woster, P.M.; Casero, R.A.
Inhibition of lysine-specific demethylase 1 by polyamine analogues results in reexpression of aberrantly silenced genes
Proc. Natl. Acad. Sci. USA
104
8023-8028
2007
Homo sapiens (O60341)
Upadhyay, A.K.; Rotili, D.; Han, J.W.; Hu, R.; Chang, Y.; Labella, D.; Zhang, X.; Yoon, Y.S.; Mai, A.; Cheng, X.
An analog of BIX-01294 selectively inhibits a family of histone H3 lysine 9 Jumonji demethylases
J. Mol. Biol.
416
319-327
2012
Homo sapiens (Q6ZMT4)
Jones, D.; Wilson, L.; Thomas, H.; Gaughan, L.; Wade, M.A.
The histone demethylase enzymes KDM3A and KDM4B co-operatively regulate chromatin transactions of the estrogen receptor in breast cancer
Cancers (Basel)
11
1122
2019
Homo sapiens (Q9Y4C1)
Ding, G.; Xu, X.; Li, D.; Chen, Y.; Wang, W.; Ping, D.; Jia, S.; Cao, L.
Fisetin inhibits proliferation of pancreatic adenocarcinoma by inducing DNA damage via RFXAP/KDM4A-dependent histone H3K36 demethylation
Cell Death Dis.
11
893
2020
Homo sapiens (O75164)
Zhou, J.; Wang, F.; Xu, C.; Zhou, Z.; Zhang, W.
The histone demethylase JMJD2A regulates the expression of BDNF and mediates neuropathic pain in mice
Exp. Cell Res.
361
155-162
2017
Homo sapiens (O75164), Mus musculus (Q8BW72), Mus musculus
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