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Information on EC 1.14.11.27 - [histone H3]-dimethyl-L-lysine36 demethylase and Organism(s) Homo sapiens and UniProt Accession O75164
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1.14.11.27 [histone H3]-dimethyl-L-lysine36 demethylaseIUBMB Comments
Requires iron(II). Of the seven potential methylation sites in histones H3 (K4, K9, K27, K36, K79) and H4 (K20, R3) from HeLa cells, the enzyme is specific for Lys36. Lysine residues exist in three methylation states (mono-, di- and trimethylated). The enzyme preferentially demethylates the dimethyl form of Lys36 (K36me2), which is its natural substrate, to form the monomethylated and unmethylated forms of Lys36. It can also demethylate monomethylated (but not the trimethylated) Lys36. cf. EC 1.14.11.69, [histone H3]-trimethyl-L-lysine36 demethylase.
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Word Map
- 1.14.11.27
- demethylases
- chromatin
-
demethylation
-
h3k9me3
-
trimethylation
-
jumonji
- tumorigenesis
- methyltransferases
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lysine-specific
- heterochromatin
-
tri-methylated
-
tudor
-
chromatin-modifying
- jmjd1a
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jmjc-domain-containing
- setdb1
The taxonomic range for the selected organisms is: Homo sapiens
The expected taxonomic range for this enzyme is: Eukaryota, Bacteria
The expected taxonomic range for this enzyme is: Eukaryota, Bacteria
Reaction Schemes
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Synonyms
jmjd2a, kdm4b, kdm2b, kdm4a, kdm2a, kdm4c, lysine demethylase, jmjd5, kdm4d, gasc1, 
more
topSYNONYM 
ORGANISM
UNIPROT
COMMENTARY 
LITERATURE
H3K36 demethylase
SYSTEMATIC NAME
IUBMB Comments
[histone H3]-N6,N6-dimethyl-L-lysine36,2-oxoglutarate:oxygen oxidoreductase
Requires iron(II). Of the seven potential methylation sites in histones H3 (K4, K9, K27, K36, K79) and H4 (K20, R3) from HeLa cells, the enzyme is specific for Lys36. Lysine residues exist in three methylation states (mono-, di- and trimethylated). The enzyme preferentially demethylates the dimethyl form of Lys36 (K36me2), which is its natural substrate, to form the monomethylated and unmethylated forms of Lys36. It can also demethylate monomethylated (but not the trimethylated) Lys36. cf. EC 1.14.11.69, [histone H3]-trimethyl-L-lysine36 demethylase.
CAS REGISTRY NUMBER
COMMENTARY
55071-98-2
-
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
histone H3 N6,N6,N6-trimethyl-L-lysine26 + 2-oxoglutarate + O2
histone H3 N6,N6-dimethyl-L-lysine26 + succinate + formaldehyde + CO2
-
-
-
?
histone H3 N6,N6,N6-trimethyl-L-lysine36 + 2-oxoglutarate + O2
histone H3 N6,N6-dimethyl-L-lysine36 + succinate + formaldehyde + CO2
-
-
-
?
histone H3-N6,N6,N6-trimethyl-L-lysine36 + 2-oxoglutarate + O2
histone H3-N6,N6-dimethyl-L-lysine36 + succinate + formaldehyde + CO2
histone H3-N6,N6-dimethyl-L-lysine36 + 2-oxoglutarate + O2
histone H3-N6-methyl-L-lysine36 + succinate + formaldehyde + CO2
histone H3 N6,N6,N6-trimethyl-L-lysine36 + 2-oxoglutarate + O2
histone H3 N6,N6-dimethyl-L-lysine36 + 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-lysine36 + 2-oxoglutarate + O2
histone H3-N6,N6-dimethyl-L-lysine36 + succinate + formaldehyde + CO2
histone H3-N6,N6-dimethyl-L-lysine36 + 2-oxoglutarate + O2
histone H3-N6-methyl-L-lysine36 + succinate + formaldehyde + CO2
protein C/EBPalpha-N6,N6-dimethyl-L-lysine + 2-oxoglutarate + O2
protein C/EBPalpha-N6-methyl-L-lysine + succinate + formaldehyde + CO2
protein N6,N6-dimethyl-L-lysine + 2-oxoglutarate + O2
protein N6-methyl-L-lysine + succinate + formaldehyde + CO2
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specifically demethylates Lys36 of histone H3
-
-
?
protein N6-methyl-L-lysine + 2-oxoglutarate + O2
protein L-lysine + succinate + formaldehyde + CO2
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specifically demethylates Lys36 of histone H3
-
-
?
serum response factor N6-methyl-L-lysine165 + 2-oxoglutarate + O2
serum response factor L-lysine165 + succinate + formaldehyde + CO2
-
-
-
?
histone H3-N6,N6,N6-trimethyl-L-lysine36 + 2-oxoglutarate + O2
histone H3-N6,N6-dimethyl-L-lysine36 + succinate + formaldehyde + CO2
-
-
-
?
histone H3-N6,N6,N6-trimethyl-L-lysine36 + 2-oxoglutarate + O2
histone H3-N6,N6-dimethyl-L-lysine36 + succinate + formaldehyde + CO2
substrate is preferred compared to histone H3-N6,N6-dimethyl-L-lysine36
-
-
?
histone H3-N6,N6-dimethyl-L-lysine36 + 2-oxoglutarate + O2
histone H3-N6-methyl-L-lysine36 + succinate + formaldehyde + CO2
-
-
-
?
histone H3-N6,N6-dimethyl-L-lysine36 + 2-oxoglutarate + O2
histone H3-N6-methyl-L-lysine36 + succinate + formaldehyde + CO2
low activity
-
-
?
histone H3-N6,N6,N6-trimethyl-L-lysine36 + 2-oxoglutarate + O2
histone H3-N6,N6-dimethyl-L-lysine36 + succinate + formaldehyde + CO2
-
-
-
?
histone H3-N6,N6,N6-trimethyl-L-lysine36 + 2-oxoglutarate + O2
histone H3-N6,N6-dimethyl-L-lysine36 + succinate + formaldehyde + CO2
substrate is preferred compared to histone H3-N6,N6-dimethyl-L-lysine36
-
-
?
histone H3-N6,N6-dimethyl-L-lysine36 + 2-oxoglutarate + O2
histone H3-N6-methyl-L-lysine36 + succinate + formaldehyde + CO2
-
-
-
-
?
histone H3-N6,N6-dimethyl-L-lysine36 + 2-oxoglutarate + O2
histone H3-N6-methyl-L-lysine36 + succinate + formaldehyde + CO2
-
-
-
?
histone H3-N6,N6-dimethyl-L-lysine36 + 2-oxoglutarate + O2
histone H3-N6-methyl-L-lysine36 + succinate + formaldehyde + CO2
low activity
-
-
?
histone H3-N6,N6-dimethyl-L-lysine36 + 2-oxoglutarate + O2
histone H3-N6-methyl-L-lysine36 + succinate + formaldehyde + CO2
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Jhdm1a is a histone demethylase that specifically demethylates dimethylated H3K36
-
-
?
histone H3-N6,N6-dimethyl-L-lysine36 + 2-oxoglutarate + O2
histone H3-N6-methyl-L-lysine36 + succinate + formaldehyde + CO2
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KDM2b/JHDM1b is an H3K36me2-specific demethylase
-
-
?
protein C/EBPalpha-N6,N6-dimethyl-L-lysine + 2-oxoglutarate + O2
protein C/EBPalpha-N6-methyl-L-lysine + succinate + formaldehyde + CO2
-
-
-
-
?
protein C/EBPalpha-N6,N6-dimethyl-L-lysine + 2-oxoglutarate + O2
protein C/EBPalpha-N6-methyl-L-lysine + succinate + formaldehyde + CO2
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Jhdm1a actively demethylates dimethylated H3K36 on the C/EBPalpha locus
-
-
?
additional information
?
-
-
KDM4D and -E only act on H3K9, with no evidence for demethylation of H3K36, while KDM4A/B/C act on both H3K9 and, less efficiently, on H3K36-methylated substrates. No activity by all isozymes with H3K4me3, H3K9me1, and H3K27me3
-
-
?
additional information
?
-
KDM4D and -E only act on H3K9, with no evidence for demethylation of H3K36, while KDM4A/B/C act on both H3K9 and, less efficiently, on H3K36-methylated substrates. No activity by all isozymes with H3K4me3, H3K9me1, and H3K27me3
-
-
?
additional information
?
-
KDM4D and -E only act on H3K9, with no evidence for demethylation of H3K36, while KDM4A/B/C act on both H3K9 and, less efficiently, on H3K36-methylated substrates. No activity by all isozymes with H3K4me3, H3K9me1, and H3K27me3
-
-
?
additional information
?
-
-
KDM4D and -E only act on H3K9, with no evidence for demethylation of H3K36, while KDM4A/B/C act on both H3K9 and, less efficiently, on H3K36-methylated substrates. No activity by all isozymes with H3K4me3, H3K9me1, and H3K27me3
-
-
?
additional information
?
-
KDM4D and -E only act on H3K9, with no evidence for demethylation of H3K36, while KDM4A/B/C act on both H3K9 and, less efficiently, on H3K36-methylated substrates. No activity by all isozymes with H3K4me3, H3K9me1, and H3K27me3
-
-
?
additional information
?
-
KDM4D and -E only act on H3K9, with no evidence for demethylation of H3K36, while KDM4A/B/C act on both H3K9 and, less efficiently, on H3K36-methylated substrates. No activity by all isozymes with H3K4me3, H3K9me1, and H3K27me3
-
-
?
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
histone H3 N6,N6,N6-trimethyl-L-lysine26 + 2-oxoglutarate + O2
histone H3 N6,N6-dimethyl-L-lysine26 + succinate + formaldehyde + CO2
-
-
-
?
histone H3-N6,N6,N6-trimethyl-L-lysine36 + 2-oxoglutarate + O2
histone H3-N6,N6-dimethyl-L-lysine36 + succinate + formaldehyde + CO2
-
-
-
?
histone H3-N6,N6-dimethyl-L-lysine36 + 2-oxoglutarate + O2
histone H3-N6-methyl-L-lysine36 + succinate + formaldehyde + CO2
-
-
-
?
histone H3 N6,N6,N6-trimethyl-L-lysine36 + 2-oxoglutarate + O2
histone H3 N6,N6-dimethyl-L-lysine36 + 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-lysine36 + 2-oxoglutarate + O2
histone H3-N6,N6-dimethyl-L-lysine36 + succinate + formaldehyde + CO2
-
-
-
?
histone H3-N6,N6-dimethyl-L-lysine36 + 2-oxoglutarate + O2
histone H3-N6-methyl-L-lysine36 + succinate + formaldehyde + CO2
protein C/EBPalpha-N6,N6-dimethyl-L-lysine + 2-oxoglutarate + O2
protein C/EBPalpha-N6-methyl-L-lysine + succinate + formaldehyde + CO2
-
Jhdm1a actively demethylates dimethylated H3K36 on the C/EBPalpha locus
-
-
?
histone H3-N6,N6-dimethyl-L-lysine36 + 2-oxoglutarate + O2
histone H3-N6-methyl-L-lysine36 + succinate + formaldehyde + CO2
-
-
-
-
?
histone H3-N6,N6-dimethyl-L-lysine36 + 2-oxoglutarate + O2
histone H3-N6-methyl-L-lysine36 + succinate + formaldehyde + CO2
-
-
-
?
histone H3-N6,N6-dimethyl-L-lysine36 + 2-oxoglutarate + O2
histone H3-N6-methyl-L-lysine36 + succinate + formaldehyde + CO2
-
Jhdm1a is a histone demethylase that specifically demethylates dimethylated H3K36
-
-
?
histone H3-N6,N6-dimethyl-L-lysine36 + 2-oxoglutarate + O2
histone H3-N6-methyl-L-lysine36 + succinate + formaldehyde + CO2
-
KDM2b/JHDM1b is an H3K36me2-specific demethylase
-
-
?
METALS and IONS
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
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
ORGANISM
COMMENTARY
LITERATURE
UNIPROT
SEQUENCE DB
SOURCE
SOURCE TISSUE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
SOURCE
LOCALIZATION
ORGANISM
UNIPROT
COMMENTARY
GeneOntology No.
LITERATURE
SOURCE
isozyme KDM4C is associated with chromatin during mitosis, residue R919 on the proximal Tudor domains of KDM4C is critical for its association with chromatin during mitosis. KDM4C protein is localized to mitotic chromatin from prometaphase to telophase
additional information
additional information
the isozyme is not associated with chromatin during mitosis
-
additional information
the isozyme is not associated with chromatin during mitosis
-
additional information
the isozyme is not associated with chromatin during mitosis
-
additional information
the isozyme is not associated with chromatin during mitosis
-
additional information
-
the isozyme is not associated with chromatin during mitosis
-
additional information
the isozyme is not associated with chromatin during mitosis
-
additional information
the isozyme is not associated with chromatin during mitosis
-
additional information
the isozyme is not associated with chromatin during mitosis
-
additional information
the isozyme is not associated with chromatin during mitosis
-
additional information
-
the isozyme is not associated with chromatin during mitosis
-
GENERAL INFORMATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
evolution
malfunction
dysregulated expression of KDM4A-D family promotes chromosomal instabilities
physiological function
evolution
malfunction
physiological function
additional information
evolution
human JMJD2 (KDM4) H3K9 and H3K36 demethylases can be divided into members that act on both H3K9 and H3K36 and H3K9 alone, structural and phylogenetic analysis, overview. KDM4A/B/C act on both H3K9 and, less efficiently, on H3K36-methylated substrates, substrate selectivity of the human KDM4 histone demethylase subfamily, overview
evolution
two families of lysine demethylases (KDM) are identified. The KDM4 family consists of four members: KDM4A, KDM4B, KDM4C and KDM4D
physiological function
the KDM4 isozymes are involved in histone methylation, a reversible and dynamically regulated process. Various types of human cancers exhibit amplification or deletion of KDM4A-D members, which selectively demethylate lysine residues on histone H3, i.e. H3K9 and H3K36, thus implicating their activity in promoting carcinogenesis. Isozyme KDM4A is not associated with chromatin during mitosis, in contrast to isozyme KDM4C
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
evolution
human JMJD2 (KDM4) H3K9 and H3K36 demethylases can be divided into members that act on both H3K9 and H3K36 and H3K9 alone, structural and phylogenetic analysis, overview. KDM4A/B/C act on both H3K9 and, less efficiently, on H3K36-methylated substrates, substrate selectivity of the human KDM4 histone demethylase subfamily, overview
evolution
two families of lysine demethylases (KDM) are identified. The KDM4 family consists of four members: KDM4A, KDM4B, KDM4C and KDM4D
malfunction
-
depletion of Kdm2b/Jhdm1b in hematopoietic progenitors significantly impairs Hoxa9/Meis1-induced leukemic transformation. In leukemic stem cells, knockdown of Kdm2b/Jhdm1b impairs their self-renewing capability in vitro and in vivo
malfunction
-
silencing of Jhdm1a promotes liver glucose synthesis, while its exogenous expression reduces blood glucose level in vivo
malfunction
dysregulated expression of KDM4A-D family promotes chromosomal instabilities
malfunction
dysregulated expression of KDM4A-D family promotes chromosomal instabilities. Depletion or overexpression of KDM4B does not leads to an increase in the frequency of abnormal mitotic cells and has no detectable effect on mitotic chromosome segregation
malfunction
dysregulated expression of KDM4A-D family promotes chromosomal instabilities. Depletion or overexpression of KDM4C, but not KDM4B, leads to over 3fold increase in the frequency of abnormal mitotic cells showing either misaligned chromosomes at metaphase, anaphase-telophase lagging chromosomes or anaphase-telophase bridges. Overexpression of a KDM4C demethylase dead mutant has no detectable effect on mitotic chromosome segregation
physiological function
-
demethylation of H3K36 reduces DSB repair. Expression of JHDM1a decreases the association of early NHEJ repair components with an induced DSB and decreased DSB repair
physiological function
-
histone demethylase Jhdm1a regulates hepatic gluconeogenesis, regulation of gluconeogenesis by Jhdm1a requires its demethylation activity. Jhdm1a is a key negative regulator of gluconeogenic gene expression. Jhdm1a regulates the expression of a major gluconeogenic regulator, C/EBPalpha, by its USF1-dependent association with the C/EBPa promoter and its subsequent demethylation of dimethylated H3K36 on the C/EBPa lpha locus
physiological function
-
Kdm2b/Jhdm1b functions as an oncogene and plays a critical role in leukemia development and maintenance, KDM2b/JHDM1b is required for initiation and maintenance of acute myeloid leukemia. Functions of Kdm2b/Jhdm1b are mediated by its silencing of p15Ink4b expression through active demethylation of histone H3-N6,N6-dimethyl-L-lysine. Kdm2b/Jhdm1b directly regulates p15Ink4b expression in leukemic cells
physiological function
the KDM4 isozymes are involved in histone methylation, a reversible and dynamically regulated process. Various types of human cancers exhibit amplification or deletion of KDM4A-D members, which selectively demethylate lysine residues on histone H3, i.e. H3K9 and H3K36, thus implicating their activity in promoting carcinogenesis. Isozyme KDM4B is not associated with chromatin during mitosis, in contrast to isozyme KDM4C
physiological function
the KDM4 isozymes are involved in histone methylation, a reversible and dynamically regulated process. Various types of human cancers exhibit amplification or deletion of KDM4A-D members, which selectively demethylate lysine residues on histone H3, i.e. H3K9 and H3K36, thus implicating their activity in promoting carcinogenesis. Isozyme KDM4D is not associated with chromatin during mitosis, in contrast to isozyme KDM4C
physiological function
the KDM4 isozymes are involved in histone methylation, a reversible and dynamically regulated process. Various types of human cancers exhibit amplification or deletion of KDM4A-D members, which selectively demethylate lysine residues on histone H3, i.e. H3K9 and H3K36, thus implicating their activity in promoting carcinogenesis. Unlike KDM4A-B, isozyme KDM4C is associated with chromatin during mitosis. This association is accompanied by a decrease in the mitotic levels of H3K9me3. The C-terminal region, containing the Tudor domains of KDM4C, is essential for its association with mitotic chromatin, especially residue R919 on the proximal Tudor domain of KDM4C is critical for its association with chromatin during mitosis. The demethylase activity and the mitotic localization of KDM4C influence the integrity of mitotic chromosome segregation
physiological function
JMJD5 has divalent cation-dependent protease activities that preferentially cleave the tails of histones 2, 3, or 4 containing methylated arginines. After the initial specific cleavage, JMJD5 acting as aminopeptidase, progressively digests the C-terminal products. JMJD5-deficient fibroblasts exhibit dramatically increased levels of methylated arginines and histones
physiological function
JMJD5 has divalent cation-dependent protease activities that preferentially cleave the tails of histones 2, 3, or 4 containing methylated arginines. After the initial specific cleavage, JMJD5 acting as aminopeptidase, progressively digests the C-terminal products. JMJD5-deficient fibroblasts exhibit dramatically increased levels of methylated arginines and histones. Depletion of JMJD7 in breast cancer cells greatly decreases cell proliferation
physiological function
JmjC domain histone H3K36me2/me1 demethylase KDM2B is highly expressed in glioblastoma surgical specimens compared to normal brain. Targeting KDM2B function genetically or pharmacologically impairs the survival of patient-derived primary glioblastoma cells through the induction of DNA damage and apoptosis and sensitizes them to chemotherapy. KDM2B loss decreases the cancer stem-like cells pool, which is potentiated by coadministration of chemotherapy
physiological function
KDM2B demethylates serum response factor residue K165 to negatively regulate muscle differentiation. KDM2B inhibits skeletal muscle differentiation by inhibiting the transcription of SRF-dependent genes. Both KDM2B and histone methyltransferase SET7 regulate the balance of SRF K165 methylation. SRF K165 methylation is required for the transcriptional activation of SRF and for the promoter occupancy of SRF-dependent genes
additional information
-
substrate selectivity is determined by multiple interactions within the catalytic domain but outside the active site, structural basis of sequence celectivity between KDM4 members, overview
additional information
substrate selectivity is determined by multiple interactions within the catalytic domain but outside the active site, structural basis of sequence celectivity between KDM4 members, overview
additional information
substrate selectivity is determined by multiple interactions within the catalytic domain but outside the active site, structural basis of sequence celectivity between KDM4 members, overview
additional information
-
ectopic expression of Kdm2b/Jhdm1b is sufficient to transform hematopoietic progenitors
additional information
-
substrate selectivity is determined by multiple interactions within the catalytic domain but outside the active site, structural basis of sequence celectivity between KDM4 members, overview
additional information
substrate selectivity is determined by multiple interactions within the catalytic domain but outside the active site, structural basis of sequence celectivity between KDM4 members, overview
additional information
substrate selectivity is determined by multiple interactions within the catalytic domain but outside the active site, structural basis of sequence celectivity between KDM4 members, overview
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). PDB
SCOP
CATH
UNIPROT
ORGANISM
SUBUNIT
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
additional information
additional information
enzyme domain structure including JmjN, JmjC, PHD and Tudor domains, overview
additional information
enzyme domain structure including JmjN, JmjC, PHD and Tudor domains, overview
additional information
enzyme domain structure including JmjN, JmjC, PHD and Tudor domains, overview
additional information
enzyme domain structure including JmjN, JmjC, PHD and Tudor domains, overview
additional information
-
enzyme domain structure including JmjN, JmjC, PHD and Tudor domains, overview
additional information
enzyme domain structure includign JmjN, JmjC, PHD and Tudor domains, overview
additional information
enzyme domain structure includign JmjN, JmjC, PHD and Tudor domains, overview
additional information
enzyme domain structure includign JmjN, JmjC, PHD and Tudor domains, overview
additional information
enzyme domain structure includign JmjN, JmjC, PHD and Tudor domains, overview
additional information
-
enzyme domain structure includign JmjN, JmjC, PHD and Tudor domains, overview
additional information
enzyme domain structure including JmjN and JmjC domains, isozyme KDM4D lacks the PHD and Tudor domains, overview
additional information
enzyme domain structure including JmjN and JmjC domains, isozyme KDM4D lacks the PHD and Tudor domains, overview
additional information
enzyme domain structure including JmjN and JmjC domains, isozyme KDM4D lacks the PHD and Tudor domains, overview
additional information
enzyme domain structure including JmjN and JmjC domains, isozyme KDM4D lacks the PHD and Tudor domains, overview
additional information
-
enzyme domain structure including JmjN and JmjC domains, isozyme KDM4D lacks the PHD and Tudor domains, overview
additional information
enzyme domain structure including JmjN, JmjC, PHD and Tudor domains, overview
additional information
enzyme domain structure including JmjN, JmjC, PHD and Tudor domains, overview
additional information
enzyme domain structure including JmjN, JmjC, PHD and Tudor domains, overview
additional information
enzyme domain structure including JmjN, JmjC, PHD and Tudor domains, overview
additional information
-
enzyme domain structure including JmjN, JmjC, PHD and Tudor domains, overview
CRYSTALLIZATION (Commentary)
ORGANISM
UNIPROT
LITERATURE
purified recombinant KDM4C, sitting drop vapor diffusion method, mixing of 7 mg/ml protein with 2 mM N-oxalylglycine with well solution, containing 25% v/v PEG 3350, 0.2 M sodium nitrate, 0.1 M Bis tris propane, pH 6.5, 5% v/v ethylene glycol, 0.01 M NiCl2, in a 2:1 ratio, 4°C, X-ray diffraction structure determination and analysis at 2.55 A resolution
PROTEIN VARIANTS
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
R919D
site-directed mutagenesis, the mutant is not associated with mitotic chromatin in contrast to the wild-type enzyme
S198M
site-directed mutagenesis, a KDM4C demethylase dead mutant
additional information
additional information
enzyme engineering and swapping of the C-terminus region containing the distal Tudor domain between isozymes KDM4C and KDM4A. Chimera5, which encodes the first 934 amino acids of KDM4C fused with the last 129 amino acid containing the distal Tudor domain of KDM4A, is excluded from mitotic chromatin. On the other hand, chimera6 that encodes the first 954 amino acids of KDM4A fused to 101 amino acids of KDM4C, which includes its distal Tudor domain, remains excluded from chromatin. The C-terminus of KDM4C containing the distal Tudor domain is essential but not sufficient for its mitotic chromatin localization
additional information
enzyme engineering and swapping of the C-terminus region containing the distal Tudor domain between isozymes KDM4C and KDM4A. Chimera5, which encodes the first 934 amino acids of KDM4C fused with the last 129 amino acid containing the distal Tudor domain of KDM4A, is excluded from mitotic chromatin. On the other hand, chimera6 that encodes the first 954 amino acids of KDM4A fused to 101 amino acids of KDM4C, which includes its distal Tudor domain, remains excluded from chromatin. The C-terminus of KDM4C containing the distal Tudor domain is essential but not sufficient for its mitotic chromatin localization
additional information
enzyme engineering and swapping of the C-terminus region containing the distal Tudor domain between isozymes KDM4C and KDM4A. Chimera5, which encodes the first 934 amino acids of KDM4C fused with the last 129 amino acid containing the distal Tudor domain of KDM4A, is excluded from mitotic chromatin. On the other hand, chimera6 that encodes the first 954 amino acids of KDM4A fused to 101 amino acids of KDM4C, which includes its distal Tudor domain, remains excluded from chromatin. The C-terminus of KDM4C containing the distal Tudor domain is essential but not sufficient for its mitotic chromatin localization
additional information
enzyme engineering and swapping of the C-terminus region containing the distal Tudor domain between isozymes KDM4C and KDM4A. Chimera5, which encodes the first 934 amino acids of KDM4C fused with the last 129 amino acid containing the distal Tudor domain of KDM4A, is excluded from mitotic chromatin. On the other hand, chimera6 that encodes the first 954 amino acids of KDM4A fused to 101 amino acids of KDM4C, which includes its distal Tudor domain, remains excluded from chromatin. The C-terminus of KDM4C containing the distal Tudor domain is essential but not sufficient for its mitotic chromatin localization
additional information
-
enzyme engineering and swapping of the C-terminus region containing the distal Tudor domain between isozymes KDM4C and KDM4A. Chimera5, which encodes the first 934 amino acids of KDM4C fused with the last 129 amino acid containing the distal Tudor domain of KDM4A, is excluded from mitotic chromatin. On the other hand, chimera6 that encodes the first 954 amino acids of KDM4A fused to 101 amino acids of KDM4C, which includes its distal Tudor domain, remains excluded from chromatin. The C-terminus of KDM4C containing the distal Tudor domain is essential but not sufficient for its mitotic chromatin localization
additional information
-
Kdm2b/Jhmd1b is required for Hoxa9/Meis1-induced leukemic transformation in vitro
additional information
-
shRNA knockdown of Jhdm1a in Hep-G2 cells elevating gluconeogenic gene expression
additional information
enzyme engineering and swapping of the C-terminus region containing the distal Tudor domain between isozymes KDM4C and KDM4A. Chimera5, which encodes the first 934 amino acids of KDM4C fused with the last 129 amino acid containing the distal Tudor domain of KDM4A, is excluded from mitotic chromatin. On the other hand, chimera6 that encodes the first 954 amino acids of KDM4A fused to 101 amino acids of KDM4C, which includes its distal Tudor domain, remains excluded from chromatin. The C-terminus of KDM4C containing the distal Tudor domain is essential but not sufficient for its mitotic chromatin localization. EGFP-KDM4CRDTF/DNLY mutant is excluded from mitotic chromatin. For isozyme knockout, U2OS cells are transfected with KDM4B-C siRNA sequences
additional information
enzyme engineering and swapping of the C-terminus region containing the distal Tudor domain between isozymes KDM4C and KDM4A. Chimera5, which encodes the first 934 amino acids of KDM4C fused with the last 129 amino acid containing the distal Tudor domain of KDM4A, is excluded from mitotic chromatin. On the other hand, chimera6 that encodes the first 954 amino acids of KDM4A fused to 101 amino acids of KDM4C, which includes its distal Tudor domain, remains excluded from chromatin. The C-terminus of KDM4C containing the distal Tudor domain is essential but not sufficient for its mitotic chromatin localization. EGFP-KDM4CRDTF/DNLY mutant is excluded from mitotic chromatin. For isozyme knockout, U2OS cells are transfected with KDM4B-C siRNA sequences
additional information
enzyme engineering and swapping of the C-terminus region containing the distal Tudor domain between isozymes KDM4C and KDM4A. Chimera5, which encodes the first 934 amino acids of KDM4C fused with the last 129 amino acid containing the distal Tudor domain of KDM4A, is excluded from mitotic chromatin. On the other hand, chimera6 that encodes the first 954 amino acids of KDM4A fused to 101 amino acids of KDM4C, which includes its distal Tudor domain, remains excluded from chromatin. The C-terminus of KDM4C containing the distal Tudor domain is essential but not sufficient for its mitotic chromatin localization. EGFP-KDM4CRDTF/DNLY mutant is excluded from mitotic chromatin. For isozyme knockout, U2OS cells are transfected with KDM4B-C siRNA sequences
additional information
enzyme engineering and swapping of the C-terminus region containing the distal Tudor domain between isozymes KDM4C and KDM4A. Chimera5, which encodes the first 934 amino acids of KDM4C fused with the last 129 amino acid containing the distal Tudor domain of KDM4A, is excluded from mitotic chromatin. On the other hand, chimera6 that encodes the first 954 amino acids of KDM4A fused to 101 amino acids of KDM4C, which includes its distal Tudor domain, remains excluded from chromatin. The C-terminus of KDM4C containing the distal Tudor domain is essential but not sufficient for its mitotic chromatin localization. EGFP-KDM4CRDTF/DNLY mutant is excluded from mitotic chromatin. For isozyme knockout, U2OS cells are transfected with KDM4B-C siRNA sequences
additional information
-
enzyme engineering and swapping of the C-terminus region containing the distal Tudor domain between isozymes KDM4C and KDM4A. Chimera5, which encodes the first 934 amino acids of KDM4C fused with the last 129 amino acid containing the distal Tudor domain of KDM4A, is excluded from mitotic chromatin. On the other hand, chimera6 that encodes the first 954 amino acids of KDM4A fused to 101 amino acids of KDM4C, which includes its distal Tudor domain, remains excluded from chromatin. The C-terminus of KDM4C containing the distal Tudor domain is essential but not sufficient for its mitotic chromatin localization. EGFP-KDM4CRDTF/DNLY mutant is excluded from mitotic chromatin. For isozyme knockout, U2OS cells are transfected with KDM4B-C siRNA sequences
PURIFICATION (Commentary)
ORGANISM
UNIPROT
LITERATURE
recombinant N-terminally His-tagged KDM4A from Escherichia coli by nickel affinity chromatography
recombinant N-terminally His-tagged KDM4B from Escherichia coli by nickel affinity chromatography
recombinant N-terminally His-tagged KDM4C from Escherichia coli by nickel affinity chromatography
CLONED (Commentary)
ORGANISM
UNIPROT
LITERATURE
gene KDM4A, recombinant expression of EGFP-tagged full-length and truncated enzymes versions
ectopic expression of Jhdm1a in HeLa and wild-type and enzyme-deficient Hep-G2 cells via lentivirus transfection
-
gene KDM4B, recombinant isozyme expression in U2OS-TetON stable cell line that conditionally expresses the fusion protein EGFP-KDM4B
gene KDM4C, recombinant isozyme expression in U2OS-TetON stable cell line that conditionally expresses the fusion protein EGFP-KDM4C, recombinant expression of EGFP-tagged full-length and truncated, andmutant enzymes versions
APPLICATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
medicine
medicine
JmjC domain histone H3K36me2/me1 demethylase KDM2B is highly expressed in glioblastoma surgical specimens compared to normal brain. Targeting KDM2B function genetically or pharmacologically impairs the survival of patient-derived primary glioblastoma cells through the induction of DNA damage and apoptosis and sensitizes them to chemotherapy. KDM2B loss decreases the cancer stem-like cells pool, which is potentiated by coadministration of chemotherapy
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
Tsukada, Y.; Fang, J.; Erdjument-Bromage, H.; Warren, M.E.; Borchers, C.H.; Tempst, P.; Zhang, Y.
Histone demethylation by a family of JmjC domain-containing proteins
Nature
439
811-816
2006
Saccharomyces cerevisiae, Homo sapiens
He, J.; Nguyen, A.T.; Zhang, Y.
KDM2b/JHDM1b, an H3K36me2-specific demethylase, is required for initiation and maintenance of acute myeloid leukemia
Blood
117
3869-3880
2011
Homo sapiens
Hillringhaus, L.; Yue, W.W.; Rose, N.R.; Ng, S.S.; Gileadi, C.; Loenarz, C.; Bello, S.H.; Bray, J.E.; Schofield, C.J.; Oppermann, U.
Structural and evolutionary basis for the dual substrate selectivity of human KDM4 histone demethylase family
J. Biol. Chem.
286
41616-41625
2011
Homo sapiens, Homo sapiens (O75164), Homo sapiens (Q9H3R0)
Pan, D.; Mao, C.; Zou, T.; Yao, A.Y.; Cooper, M.P.; Boyartchuk, V.; Wang, Y.X.
The histone demethylase Jhdm1a regulates hepatic gluconeogenesis
PLoS Genet.
8
e1002761
2012
Homo sapiens, Mus musculus, Mus musculus C57/BL6J
Fnu, S.; Williamson, E.; De Haro, L.; Brenneman, M.; Wray, J.; Shaheen, M.; Radhakrishnan, K.; Lee, S.; Nickoloff, J.; Hromas, R.
Methylation of histone H3 lysine 36 enhances DNA repair by nonhomologous end-joining
Proc. Natl. Acad. Sci. USA
108
540-545
2011
Homo sapiens
Kupershmit, I.; Khoury-Haddad, H.; Awwad, S.W.; Guttmann-Raviv, N.; Ayoub, N.
KDM4C (GASC1) lysine demethylase is associated with mitotic chromatin and regulates chromosome segregation during mitosis
Nucleic Acids Res.
42
6168-6182
2014
Homo sapiens (O75164), Homo sapiens (O94953), Homo sapiens (Q6B0I6), Homo sapiens (Q9H3R0), Homo sapiens
Liu, H.; Wang, C.; Lee, S.; Deng, Y.; Wither, M.; Oh, S.; Ning, F.; Dege, C.; Zhang, Q.; Liu, X.; Johnson, A.M.; Zang, J.; Chen, Z.; Janknecht, R.; Hansen, K.; Marrack, P.; Li, C.Y.; Kappler, J.W.; Hagman, J.; Zhang, G.
Clipping of arginine-methylated histone tails by JMJD5 and JMJD7
Proc. Natl. Acad. Sci. USA
114
E7717-E7726
2017
Homo sapiens (P0C870), Homo sapiens (Q8N371)
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
Kwon, D.H.; Kang, J.Y.; Joung, H.; Kim, J.Y.; Jeong, A.; Min, H.K.; Shin, S.; Lee, Y.G.; Kim, Y.K.; Seo, S.B.; Kook, H.
SRF is a nonhistone methylation target of KDM2B and SET7 in the regulation of skeletal muscle differentiation
Exp. Mol. Med.
53
250-263
2021
Homo sapiens (Q8NHM5)
Staberg, M.; Rasmussen, R.D.; Michaelsen, S.R.; Pedersen, H.; Jensen, K.E.; Villingshoj, M.; Skjoth-Rasmussen, J.; Brennum, J.; Vitting-Seerup, K.; Poulsen, H.S.; Hamerlik, P.
Targeting glioma stem-like cell survival and chemoresistance through inhibition of lysine-specific histone demethylase KDM2B
Mol. Oncol.
12
406-420
2018
Homo sapiens (Q8NHM5)
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