Page last updated: 2024-10-24

histone H3K9me2/H3K9me3 demethylase activity

Definition

Target type: molecularfunction

Catalysis of the removal of a methyl group from a tri or a dimethyl-lysine residue at position 9 of the histone H3 protein. This is a dioxygenase reaction that is dependent on Fe(II) and 2-oxoglutarate. [PMID:20208542, PMID:20531378]

Histone H3K9me2/H3K9me3 demethylase activity is a critical molecular function in the regulation of chromatin structure and gene expression. It involves the removal of two or three methyl groups from lysine 9 on histone H3 (H3K9), catalyzed by specific enzymes known as demethylases. This activity plays a crucial role in modulating the accessibility of DNA to transcription factors, thereby influencing the transcription of genes.

H3K9 methylation is a well-established epigenetic mark associated with gene silencing. When H3K9 is methylated, it recruits proteins that compact chromatin, making the DNA less accessible to transcriptional machinery. Conversely, histone H3K9 demethylase activity removes these methyl groups, leading to chromatin decondensation and increased gene transcription.

There are two main classes of H3K9 demethylases: lysine-specific demethylase 1 (LSD1) and the jumonji C (JmjC) domain-containing demethylases. LSD1 specifically removes mono- and dimethylated H3K9 (H3K9me1 and H3K9me2), while JmjC domain-containing demethylases can remove mono-, di-, and trimethylated H3K9 (H3K9me1, H3K9me2, and H3K9me3).

The specific activity of H3K9 demethylases is tightly regulated by various factors, including cellular context, developmental stage, and signaling pathways. Dysregulation of this activity is implicated in several diseases, including cancer, neurodevelopmental disorders, and immune disorders. Understanding the intricate interplay between H3K9 methylation and demethylation is essential for deciphering the complexities of gene regulation and its implications for human health.'
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Proteins (6)

ProteinDefinitionTaxonomy
Lysine-specific demethylase 4CA lysine-specific demethylase 4C that is encoded in the genome of human. [PRO:DNx, UniProtKB:Q9H3R0]Homo sapiens (human)
Lysine-specific demethylase 4CA lysine-specific demethylase 4C that is encoded in the genome of human. [PRO:DNx, UniProtKB:Q9H3R0]Homo sapiens (human)
Lysine-specific demethylase 4DA lysine-specific demethylase 4D that is encoded in the genome of human. [PRO:DNx, UniProtKB:Q6B0I6]Homo sapiens (human)
Lysine-specific demethylase 4BA lysine-specific demethylase 4B that is encoded in the genome of human. [PRO:DNx, UniProtKB:O94953]Homo sapiens (human)
Lysine-specific demethylase 4AA lysine-specific demethylase 4A that is encoded in the genome of human. [PRO:DNx, UniProtKB:O75164]Homo sapiens (human)
Lysine-specific demethylase 4EA lysine-specific demethylase 4E that is encoded in the genome of human. [PRO:DNx, UniProtKB:B2RXH2]Homo sapiens (human)

Compounds (37)

CompoundDefinitionClassesRoles
butyric acidbutyrate : A short-chain fatty acid anion that is the conjugate base of butyric acid, obtained by deprotonation of the carboxy group.

butyric acid : A straight-chain saturated fatty acid that is butane in which one of the terminal methyl groups has been oxidised to a carboxy group.

Butyric Acid: A four carbon acid, CH3CH2CH2COOH, with an unpleasant odor that occurs in butter and animal fat as the glycerol ester.
fatty acid 4:0;
straight-chain saturated fatty acid
human urinary metabolite;
Mycoplasma genitalium metabolite
pyrazole1H-pyrazole : The 1H-tautomer of pyrazole.pyrazole
quinolinic acidpyridinedicarboxylic acid : Any member of the class of pyridines carrying two carboxy groups.

quinolinic acid : A pyridinedicarboxylic acid that is pyridine substituted by carboxy groups at positions 2 and 3. It is a metabolite of tryptophan.

Quinolinic Acid: A metabolite of tryptophan with a possible role in neurodegenerative disorders. Elevated CSF levels of quinolinic acid are correlated with the severity of neuropsychological deficits in patients who have AIDS.
pyridinedicarboxylic acidEscherichia coli metabolite;
human metabolite;
mouse metabolite;
NMDA receptor agonist
succinic acidsuccinic acid : An alpha,omega-dicarboxylic acid resulting from the formal oxidation of each of the terminal methyl groups of butane to the corresponding carboxy group. It is an intermediate metabolite in the citric acid cycle.

Succinic Acid: A water-soluble, colorless crystal with an acid taste that is used as a chemical intermediate, in medicine, the manufacture of lacquers, and to make perfume esters. It is also used in foods as a sequestrant, buffer, and a neutralizing agent. (Hawley's Condensed Chemical Dictionary, 12th ed, p1099; McGraw-Hill Dictionary of Scientific and Technical Terms, 4th ed, p1851)
alpha,omega-dicarboxylic acid;
C4-dicarboxylic acid
anti-ulcer drug;
fundamental metabolite;
micronutrient;
nutraceutical;
radiation protective agent
ciclopiroxcyclic hydroxamic acid;
hydroxypyridone antifungal drug;
pyridone
antibacterial agent;
antiseborrheic
deferipronedeferiprone : A member of the class of 4-pyridones that is pyridin-4(1H)-one substituted at positions 1 and 2 by methyl groups and at position 3 by a hydroxy group. A lipid-soluble iron-chelator used for treatment of thalassaemia.

Deferiprone: A pyridone derivative and iron chelator that is used in the treatment of IRON OVERLOAD in patients with THALASSEMIA.
4-pyridonesiron chelator;
protective agent
deferoxamineDeferoxamine: Natural product isolated from Streptomyces pilosus. It forms iron complexes and is used as a chelating agent, particularly in the mesylate form.

desferrioxamine B : An acyclic desferrioxamine that is butanedioic acid in which one of the carboxy groups undergoes formal condensation with the primary amino group of N-(5-aminopentyl)-N-hydroxyacetamide and the second carboxy group undergoes formal condensation with the hydroxyamino group of N(1)-(5-aminopentyl)-N(1)-hydroxy-N(4)-[5-(hydroxyamino)pentyl]butanediamide. It is a siderophore native to Streptomyces pilosus biosynthesised by the DesABCD enzyme cluster as a high affinity Fe(III) chelator.
acyclic desferrioxaminebacterial metabolite;
ferroptosis inhibitor;
iron chelator;
siderophore
fenoldopamFenoldopam: A dopamine D1 receptor agonist that is used as an antihypertensive agent. It lowers blood pressure through arteriolar vasodilation.benzazepinealpha-adrenergic agonist;
antihypertensive agent;
dopamine agonist;
dopaminergic antagonist;
vasodilator agent
beta-lapachonebeta-lapachone : A benzochromenone that is 3,4-dihydro-2H-benzo[h]chromene-5,6-dione substituted by geminal methyl groups at position 2. Isolated from Tabebuia avellanedae, it exhibits antineoplastic and anti-inflammatory activities.

beta-lapachone: antineoplastic inhibitor of reverse transcriptase, DNA topoisomerase, and DNA polymerase
benzochromenone;
orthoquinones
anti-inflammatory agent;
antineoplastic agent;
plant metabolite
nitrazepamnitrazepam : A 1,4-benzodiazepinone that is 1,3-dihydro-2H-1,4-benzodiazepin-2-one which is substituted at positions 5 and 7 by phenyl and nitro groups, respectively. It is used as a hypnotic for the short-term management of insomnia and for the treatment of epileptic spasms in infants (West's syndrome).

Nitrazepam: A benzodiazepine derivative used as an anticonvulsant and hypnotic.
1,4-benzodiazepinone;
C-nitro compound
anticonvulsant;
antispasmodic drug;
drug metabolite;
GABA modulator;
sedative
vorinostatvorinostat : A dicarboxylic acid diamide comprising suberic (octanedioic) acid coupled to aniline and hydroxylamine. A histone deacetylase inhibitor, it is marketed under the name Zolinza for the treatment of cutaneous T cell lymphoma (CTCL).

Vorinostat: A hydroxamic acid and anilide derivative that acts as a HISTONE DEACETYLASE inhibitor. It is used in the treatment of CUTANEOUS T-CELL LYMPHOMA and SEZARY SYNDROME.
dicarboxylic acid diamide;
hydroxamic acid
antineoplastic agent;
apoptosis inducer;
EC 3.5.1.98 (histone deacetylase) inhibitor
succinylacetone4,6-dioxoheptanoic acid : A dioxo monocarboxylic acid that is heptanoic acid in which oxo groups replace the hydrogens at positions 4 and 6. It is an abnormal metabolite of the tyrosine metabolic pathway and a marker for type 1 tyrosinaemia.

succinylacetone: inhibitor of heme biosynthesis
beta-diketone;
dioxo monocarboxylic acid
human metabolite
2,5-pyridinedicarboxylic acid2,5-Pyridinedicarboxylic acid: RN given refers to parent cpd

isocinchomeronic acid : A pyridinedicarboxylic acid carrying carboxy groups at positions 2 and 5.
pyridinedicarboxylic acid
3,4-pyridinedicarboxylic acid3,4-pyridinedicarboxylic acid: structure in first sourcepyridinedicarboxylic acid
2,4-pyridinedicarboxylic acidlutidinic acid : A pyridinedicarboxylic acid carrying carboxy groups at positions 2 and 4.pyridinedicarboxylic acid
3,5-pyridinedicarboxylic acid3,5-pyridinedicarboxylic acid: structure in first sourcepyridinedicarboxylic acid
dipicolinic aciddipicolinic acid : A pyridinedicarboxylic acid carrying two carboxy groups at positions 2 and 6.pyridinedicarboxylic acidbacterial metabolite
daminozidedaminozide: induces tumorsstraight-chain fatty acid
carbidopacatechols;
hydrate;
hydrazines;
monocarboxylic acid
antidyskinesia agent;
antiparkinson drug;
dopaminergic agent;
EC 4.1.1.28 (aromatic-L-amino-acid decarboxylase) inhibitor
toxoflavintoxoflavin : A pyrimidotriazine that is 1,6-dimethyl-1,5,6,7-tetrahydropyrimido[5,4-e][1,2,4]triazine with oxo groups at positions 5 and 7.

toxoflavin: azapteridine antibiotic; structure
carbonyl compound;
pyrimidotriazine
antibacterial agent;
antineoplastic agent;
apoptosis inducer;
bacterial metabolite;
toxin;
virulence factor;
Wnt signalling inhibitor
n-acetylglutamic acidN-acetyl-L-glutamic acid : An N-acyl-L-amino acid that is L-glutamic acid in which one of the amine hydrogens is substituted by an acetyl group.

N-acetylglutamic acid: RN given refers to (L)-isomer
N-acetyl-L-amino acid;
N-acyl-L-glutamic acid
human metabolite;
Saccharomyces cerevisiae metabolite
di-n-desethylamiodaronedi-N-desethylamiodarone: amiodarone metabolite in dogs; structure given in first source
deferasiroxdeferasirox : A member of the class of triazoles, deferasirox is 1,2,4-triazole substituted by a 4-carboxyphenyl group at position 1 and by 2-hydroxyphenyl groups at positions 3 and 5. An orally active iron chelator, it is used to manage chronic iron overload in patients receiving long-term blood transfusions.

Deferasirox: A triazole and benzoate derivative that acts as a selective iron chelator. It is used in the management of chronic IRON OVERLOAD due to blood transfusion or non-transfusion dependent THALASSEMIA.
benzoic acids;
monocarboxylic acid;
phenols;
triazoles
iron chelator
d-2-hydroxyglutarate(R)-2-hydroxyglutaric acid : The (R)-enantiomer of 2-hydroxyglutaric acid.2-hydroxyglutaric acidalgal metabolite
alpha-hydroxyglutarate, (l)-isomer2-hydroxyglutaric acid
trichostatin atrichostatin A: chelates zinc ion in the active site of histone deacetylases, resulting in preventing histone unpacking so DNA is less available for transcription; do not confuse with TRICHOSANTHIN which is a protein; found in STREPTOMYCESantibiotic antifungal agent;
hydroxamic acid;
trichostatin
bacterial metabolite;
EC 3.5.1.98 (histone deacetylase) inhibitor;
geroprotector
fumaric acidfumaric acid : A butenedioic acid in which the C=C double bond has E geometry. It is an intermediate metabolite in the citric acid cycle.

fumaric acid: see also record for ferrous fumarate; use FUMARATES for general fumaric acid esters
butenedioic acidfood acidity regulator;
fundamental metabolite;
geroprotector
5-carboxy-8-hydroxyquinoline5-carboxy-8-hydroxyquinoline: a JmjC histone demethylase inhibitor; structure in first sourcequinolines
(1R,2S)-tranylcypromine hydrochloride(1R,2S)-tranylcypromine hydrochloride : A hydrochloride obtained by combining (1R,2S)-tranylcypromine with one equivalent of hydrochloric acid.hydrochloride
N-[2-furanyl-(8-hydroxy-7-quinolinyl)methyl]-2-methylpropanamidehydroxyquinoline
oxalylglycineN-oxalylglycine : An amino dicarboxylic acid that is iminodiacetic acid with an oxo substituent. It is used as an inhibitor of alpha-ketoglutarate dependent (EC 1.14.11.*) enzymes.

oxalylglycine: structure given in first source
amino dicarboxylic acid;
N-acylglycine
EC 1.14.11.* (oxidoreductase acting on paired donors, 2-oxoglutarate as one donor, incorporating 1 atom each of oxygen into both donors) inhibitor
baicaleintrihydroxyflavoneangiogenesis inhibitor;
anti-inflammatory agent;
antibacterial agent;
anticoronaviral agent;
antifungal agent;
antineoplastic agent;
antioxidant;
apoptosis inducer;
EC 1.13.11.31 (arachidonate 12-lipoxygenase) inhibitor;
EC 1.13.11.33 (arachidonate 15-lipoxygenase) inhibitor;
EC 3.4.21.26 (prolyl oligopeptidase) inhibitor;
EC 3.4.22.69 (SARS coronavirus main proteinase) inhibitor;
EC 4.1.1.17 (ornithine decarboxylase) inhibitor;
ferroptosis inhibitor;
geroprotector;
hormone antagonist;
plant metabolite;
prostaglandin antagonist;
radical scavenger
myricetin7-hydroxyflavonol;
hexahydroxyflavone
antineoplastic agent;
antioxidant;
cyclooxygenase 1 inhibitor;
food component;
geroprotector;
hypoglycemic agent;
plant metabolite
geldanamycin1,4-benzoquinones;
ansamycin;
carbamate ester;
organic heterobicyclic compound
antimicrobial agent;
antineoplastic agent;
antiviral agent;
cysteine protease inhibitor;
Hsp90 inhibitor
17-(dimethylaminoethylamino)-17-demethoxygeldanamycin17-(dimethylaminoethylamino)-17-demethoxygeldanamycin: structure in first source

alvespimycin : A 19-membered macrocyle that is geldanamycin in which the methoxy group attached to the benzoquinone moiety has been replaced by a 2-(N,N-dimethylamino)ethylamino group.
1,4-benzoquinones;
ansamycin;
carbamate ester;
secondary amino compound;
tertiary amino compound
Hsp90 inhibitor
tanespimycinCP 127374: analog of herbimycin A1,4-benzoquinones;
ansamycin;
carbamate ester;
organic heterobicyclic compound;
secondary amino compound
antineoplastic agent;
apoptosis inducer;
Hsp90 inhibitor
3-[[2-(2-pyridinyl)-6-(1,2,4,5-tetrahydro-3-benzazepin-3-yl)-4-pyrimidinyl]amino]propanoic acidorganonitrogen heterocyclic compound