Literature summary for 1.14.11.69 extracted from

Black, J.C.; Manning, A.L.; Van Rechem, C.; Kim, J.; Ladd, B.; Cho, J.; Pineda, C.M.; Murphy, N.; Daniels, D.L.; Montagna, C.; Lewis, P.W.; Glass, K.; Allis, C.D.; Dyson, N.J.; Getz, G.; Whetstine, J.R.
KDM4A lysine demethylase induces site-specific copy gain and rereplication of regions amplified in tumors (2013), Cell, 154, 541-555 .

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Application

Application	Comment	Organism
medicine	KDM4A is both amplified and deleted across many disparate cancer types, and KDM4A expression correlates with copy number in these samples. 46% of ovarian cancer cells display KDM4A amplification, which correlates with expression	Homo sapiens

Cloned(Commentary)

Cloned (Comment)	Organism
gene KDM4A, transient recombinant overexpression in RPE cells	Homo sapiens

Localization

Localization	Comment	Organism	GeneOntology No.	Textmining
nucleus	-	Homo sapiens	5634	-

Natural Substrates/ Products (Substrates)

Natural Substrates	Organism	Comment (Nat. Sub.)	Natural Products	Comment (Nat. Pro.)	Rev.	Reac.
[histone H3]-N6,N6,N6-trimethyl-L-lysine 36 + 2-oxoglutarate + O2	Homo sapiens	-	[histone H3]-N6,N6-dimethyl-L-lysine 36 + succinate + formaldehyde + CO2	-	?
[histone H3]-N6,N6-dimethyl-L-lysine 36 + 2-oxoglutarate + O2	Homo sapiens	-	[histone H3]-N6-methyl-L-lysine 36 + succinate + formaldehyde + CO2	-	?

Organism

Organism	UniProt	Comment	Textmining
Homo sapiens	O75164	-	-

Source Tissue

Source Tissue	Comment	Organism	Textmining
carcinoma cell	KDM4A is amplified and overexpressed in cancer cells of several tumor types	Homo sapiens	-

Substrates and Products (Substrate)

Substrates	Comment Substrates	Organism	Products	Comment (Products)	Rev.	Reac.
additional information	bifunctional H3K9/36me3 lysine demethylase KDM4A/JMJD2A acting on Lys 9 and Lys36 of histone 3	Homo sapiens	?	-	?
[histone H3]-N6,N6,N6-trimethyl-L-lysine 36 + 2-oxoglutarate + O2	-	Homo sapiens	[histone H3]-N6,N6-dimethyl-L-lysine 36 + succinate + formaldehyde + CO2	-	?
[histone H3]-N6,N6-dimethyl-L-lysine 36 + 2-oxoglutarate + O2	-	Homo sapiens	[histone H3]-N6-methyl-L-lysine 36 + succinate + formaldehyde + CO2	-	?

Synonyms

Synonyms	Comment	Organism
H3K9/36me3 lysine demethylase	-	Homo sapiens
KDM4A lysine demethylase	-	Homo sapiens
KDM4A/JMJD2A	-	Homo sapiens
More	see also EC 1.14.11.66	Homo sapiens

General Information

General Information	Comment	Organism
evolution	KDM4A belongs to the KDM4 family	Homo sapiens
malfunction	KDM4A/JMJD2A overexpression leads to localized copy gain of 1q12, 1q21, and Xq13.1 without global chromosome instability, KDM4A-amplified tumors have increased copy gains for these same regions. 1q12h copy gain occurs within a single cell cycle, requires S phase, and is not stable but is regenerated each cell division. Sites with increased copy number are rereplicated and have increased KDM4A, MCM, and DNA polymerase occupancy. Suv39h1/KMT1A or HP1gamma overexpression suppresses the copy gain, whereas H3K9/K36 methylation interference promotes gain. Overexpression of a chromatin modifier results in site-specific copy gains	Homo sapiens
physiological function	H3K9me3 demethylase KDM4A/JMJD2A is able to increase accessibility and alter the replication timing at specific heterochromatic regions. KDM4A overexpression promotes copy gain of 1q12, 1q21, and Xq13.1 in cancer cells and results in site-specific copy gain of regions amplified in human tumors. These copy gains are not stably inherited but are generated transiently in each subsequent S phase and cleared by late G2. KDM4A is the only KDM4 family member that generated the gains in a catalytically dependent manner, copy gains are antagonized by coexpression of Suv39h1/KMT1A or HP1gamma, and promoted by H3K9 or H3K36 methylation interference. KDM4A associates with replication machinery and promotes rereplication of 1q12. KDM4A overexpression promotes chromatin state changes and recruitment of replication machinery. KDM4A-dependent 1q12h copy gain requires catalytic activity and Tudor domains, the KDM4A catalytic domain alone is insufficient to generate 1q12h gain	Homo sapiens
physiological function	KDM4A overexpression promotes chromatin state changes and recruitment of replication machinery and leads to localized copy gain of cytogenetic bands 1q12, 1q21, and Xq13.1 without global chromosome instability. KDM4A-amplified tumors have increased copy gains for these same regions. 1q12h copy gain occurs within a single cell cycle, requires S phase and is not stable but regenerated each cell division. Sites with increased copy number are rereplicated and have increased KDM4A, MCM and DNA polymerase occupancy. Suv39h1/KMT1A or HP1gamma overexpression suppresses the copy gain, while H3K9/K36 methylation interference promotes gain	Homo sapiens

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Release 2023.1 (January 2023)