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Information on EC 1.14.11.65 - [histone H3]-dimethyl-L-lysine9 demethylase and Organism(s) Mus musculus and UniProt Accession Q6ZQ88

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IUBMB 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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Mus musculus
UNIPROT: Q6ZQ88
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Word Map
The taxonomic range for the selected organisms is: Mus musculus
The enzyme appears in selected viruses and cellular organisms
Synonyms
hairless, kdm1a, kdm7a, lysine specific demethylase 1, lysine-specific demethylase-1, hairless protein, lysine-specific histone demethylase 1, kiaa1718, jmj27, lysine-specific demethylase 1a, more
SYNONYM
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
H3K9Me2 demethylase
-
histone demethylase
-
histone H3 Lys 9 demethylase
-
JmjC-domain-containing histone demethylase 2A
-
JMJD1B
-
-
Jmjd2c histone demethylase
-
-
lysine-specific demethylase-1
-
additional information
see also for EC 1.14.99.66
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) hide
LITERATURE
(Substrate)
COMMENTARY
(Product) hide
LITERATURE
(Product)
Reversibility
r=reversible
ir=irreversible
?=not specified
histone H3 N6,N6-dimethyl-L-lysine9 + 2-oxoglutarate + O2
histone H3 N6-methyl-L-lysine9 + succinate + formaldehyde + CO2
show the reaction diagram
-
-
-
?
histone H3 N6-methyl-L-lysine9 + 2-oxoglutarate + O2
histone H3 L-lysine9 + succinate + formaldehyde + CO2
show the reaction diagram
-
-
-
?
[histone H3]-N6,N6-dimethyl-L-lysine 9 + 2-oxoglutarate + O2
[histone H3]-N6-methyl-L-lysine 9 + succinate + formaldehyde + CO2
show the reaction diagram
[histone H3]-N6,N6-dimethyl-L-lysine9 + 2 2-oxoglutarate + 2 O2
[histone H3]-L-lysine9 + 2 succinate + 2 formaldehyde + 2 CO2
show the reaction diagram
[histone H3]-N6-methyl-L-lysine 9 + 2-oxoglutarate + O2
[histone H3]-L-lysine 9 + succinate + formaldehyde + CO2
show the reaction diagram
additional information
?
-
NATURAL SUBSTRATE
NATURAL PRODUCT
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate) hide
LITERATURE
(Substrate)
COMMENTARY
(Product) hide
LITERATURE
(Product)
REVERSIBILITY
r=reversible
ir=irreversible
?=not specified
histone H3 N6,N6-dimethyl-L-lysine9 + 2-oxoglutarate + O2
histone H3 N6-methyl-L-lysine9 + succinate + formaldehyde + CO2
show the reaction diagram
-
-
-
?
histone H3 N6-methyl-L-lysine9 + 2-oxoglutarate + O2
histone H3 L-lysine9 + succinate + formaldehyde + CO2
show the reaction diagram
-
-
-
?
[histone H3]-N6,N6-dimethyl-L-lysine 9 + 2-oxoglutarate + O2
[histone H3]-N6-methyl-L-lysine 9 + succinate + formaldehyde + CO2
show the reaction diagram
[histone H3]-N6,N6-dimethyl-L-lysine9 + 2 2-oxoglutarate + 2 O2
[histone H3]-L-lysine9 + 2 succinate + 2 formaldehyde + 2 CO2
show the reaction diagram
-
Jmjd2c is recruited to the P2 promoter region of Mdm2 gene resulting in demethylation of histone H3 lysine 9, as typically found in actively transcribed genes
-
-
?
[histone H3]-N6-methyl-L-lysine 9 + 2-oxoglutarate + O2
[histone H3]-L-lysine 9 + succinate + formaldehyde + CO2
show the reaction diagram
additional information
?
-
Kdm3a can specifically remove mono- or di-methyl residues from H3K9me1 or H3K9me2 to regulate gene transcription
-
-
?
COFACTOR
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
FAD
dependent on
METALS and IONS
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
Fe2+
required for catalysis
ACTIVATING COMPOUND
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
ascorbate
-
ORGANISM
COMMENTARY hide
LITERATURE
UNIPROT
SEQUENCE DB
SOURCE
SOURCE TISSUE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
SOURCE
the enzyme is mainly distributed in luminal epithelial cells of wild-type mammary glands
Manually annotated by BRENDA team
olfactory-placode-derived cell line, OP-6
Manually annotated by BRENDA team
protein level is the highest in round spermatids, compared with spermatocyte and elogating spermatids
Manually annotated by BRENDA team
high expression at both mRNA and protein level, significant increase during spermatogenesis. Expression during and after meiosis, preceding the expression of transition proteins and protamines
Manually annotated by BRENDA team
additional information
LOCALIZATION
ORGANISM
UNIPROT
COMMENTARY hide
GeneOntology No.
LITERATURE
SOURCE
GENERAL INFORMATION
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
evolution
KDM3A is a histone demethylase in the JmjC domain-containing protein family
malfunction
metabolism
expression of histone H3 Lys 9 demethylases Jmjd1a and Jmjd2c (EC 1.14.11.66) is positively correlated with the pluripotent state of ES and iPS cells. Jmjd1a and Jmjd2c regulate the global levels of H3K9Me2 and H3K9Me3, respectively
physiological function
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?
KDM1A_MOUSE
853
0
92851
Swiss-Prot
-
PROTEIN VARIANTS
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
H1560A/D1562A/H1689A
-
catalytically inactive mutant, carries mutations in the conserved cofactor (Fe2+) binding site
H190A
-
inactive mutant
additional information
CLONED (Commentary)
ORGANISM
UNIPROT
LITERATURE
expression of FLAG-tagged wild-type and H190A mutant Jmjd2c in mouse embryonic fibroblasts
-
gene KDM3A, cloning of the Jmjd1a intronic DNA containing the Oct4-binding sites upstream of or downstream from a luciferase reporter to test for enhancer activity, robust enhancer activity is observed when the constructs is transfected into ES cells, real-time PCR expression analysis
EXPRESSION
ORGANISM
UNIPROT
LITERATURE
expression is positively regulated by the embryonic stem cell transcription factor Oct4
gene Jmjd1a is positively regulated by the ES cell transcription factor Oct4
Jhdm2a expression is induced by beta-adrenergic stimulation
mRNA and protein levels of Jmjd2a are significantly increased in the neurons of mouse undergoing neuropathic pain
APPLICATION
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
medicine
JMJD2A responds to neuropathic pain and participates in the maintenance of neuropathic pain. The mRNA and protein levels of Jmjd2a are significantly increased in the neurons of mouse undergoing neuropathic pain. 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. JMJD2A promotes the expression of Bdnf during neuropathic pain and neuron-specific knockout of Jmjd2a blocks the hypersensitivity of mice undergoing chronic neuropathic pain
REF.
AUTHORS
TITLE
JOURNAL
VOL.
PAGES
YEAR
ORGANISM (UNIPROT)
PUBMED ID
SOURCE
Okada, Y.; Scott, G.; Ray, M.K.; Mishina, Y.; Zhang, Y.
Histone demethylase JHDM2A is critical for Tnp1 and Prm1 transcription and spermatogenesis
Nature
450
119-123
2007
Mus musculus (Q6PCM1)
Manually annotated by BRENDA team
Ishimura, A.; Terashima, M.; Kimura, H.; Akagi, K.; Suzuki, Y.; Sugano, S.; Suzuki, T.
Jmjd2c histone demethylase enhances the expression of Mdm2 oncogene
Biochem. Biophys. Res. Commun.
389
366-371
2009
Mus musculus
Manually annotated by BRENDA team
Liu, Z.; Chen, X.; Zhou, S.; Liao, L.; Jiang, R.; Xu, J.
The histone H3K9 demethylase Kdm3b is required for somatic growth and female reproductive function
Int. J. Biol. Sci.
11
494-507
2015
Mus musculus (Q6ZPY7)
Manually annotated by BRENDA team
Vyas, R.N.; Meredith, D.; Lane, R.P.
Lysine-specific demethylase-1 (LSD1) depletion disrupts monogenic and monoallelic odorant receptor (OR) expression in an olfactory neuronal cell line
Mol. Cell. Neurosci.
82
1-11
2017
Mus musculus (Q6ZQ88)
Manually annotated by BRENDA team
Qin, L.; Xu, Y.; Yu, X.; Toneff, M.; Li, D.; Liao, L.; Martinez, J.; Li, Y.; Xu, J.
The histone demethylase Kdm3a is required for normal epithelial proliferation ductal elongation and tumor growth in the mouse mammary gland
Oncotarget
8
84761-84775
2017
Mus musculus (Q6PCM1)
Manually annotated by BRENDA team
Li, S.; Ali, S.; Duan, X.; Liu, S.; Du, J.; Liu, C.; Dai, H.; Zhou, M.; Zhou, L.; Yang, L.; Chu, P.; Li, L.; Bhatia, R.; Schones, D.; Wu, X.; Xu, H.; Hua, Y.; Guo, Z.; Yang, Y.; Zheng, L.; Shen, B.
JMJD1B demethylates H4R3me2s and H3K9me2 to facilitate gene expression for development of hematopoietic stem and progenitor cells
Cell Rep.
23
389-403
2018
Mus musculus
Manually annotated by BRENDA team
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)
Manually annotated by BRENDA team
Tachibana, M.; Nozaki, M.; Takeda, N.; Shinkai, Y.
Functional dynamics of H3K9 methylation during meiotic prophase progression
EMBO J.
26
3346-3359
2007
Mus musculus (Q6PCM1)
Manually annotated by BRENDA team
Loh, Y.; Zhang, W.; Chen, X.; George, J.; Ng, H.
Jmjd1a and Jmjd2c histone H3 Lys 9 demethylases regulate self-renewal in embryonic stem cells
Genes Dev.
21
2545-2557
2007
Mus musculus (Q6PCM1)
Manually annotated by BRENDA team
Loh, Y.H.; Zhang, W.; Chen, X.; George, J.; Ng, H.H.
Jmjd1a and Jmjd2c histone H3 Lys 9 demethylases regulate self-renewal in embryonic stem cells
Genes Dev.
21
254525-57
2007
Mus musculus (Q6PCM1)
Manually annotated by BRENDA team
Tateishi, K.; Okada, Y.; Kallin, E.; Zhang, Y.
Role of Jhdm2a in regulating metabolic gene expression and obesity resistance
Nature
458
757-761
2009
Mus musculus (Q6PCM1)
Manually annotated by BRENDA team
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
Manually annotated by BRENDA team
Zhang, Q.J.; Tran, T.A.T.; Wang, M.; Ranek, M.J.; Kokkonen-Simon, K.M.; Gao, J.; Luo, X.; Tan, W.; Kyrychenko, V.; Liao, L.; Xu, J.; Hill, J.A.; Olson, E.N.; Kass, D.A.; Martinez, E.D.; Liu, Z.P.
Histone lysine dimethyl-demethylase KDM3A controls pathological cardiac hypertrophy and fibrosis
Nat. Commun.
9
5230
2018
Mus musculus (Q6PCM1)
Manually annotated by BRENDA team