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Literature summary for 1.14.11.27 extracted from

  • 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 (2014), Nucleic Acids Res., 42, 6168-6182 .
    View publication on PubMedView publication on EuropePMC

Cloned(Commentary)

Cloned (Comment) Organism
gene KDM4A, recombinant expression of EGFP-tagged full-length and truncated enzymes versions Homo sapiens
gene KDM4B, recombinant isozyme expression in U2OS-TetON stable cell line that conditionally expresses the fusion protein EGFP-KDM4B Homo sapiens
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 Homo sapiens
gene KDM4D is Y chromosome encoded and a truncated enzyme variant compared to KDM4A-C Homo sapiens

Protein Variants

Protein Variants Comment Organism
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 Homo sapiens
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 Homo sapiens
R919D site-directed mutagenesis, the mutant is not associated with mitotic chromatin in contrast to the wild-type enzyme Homo sapiens
S198M site-directed mutagenesis, a KDM4C demethylase dead mutant Homo sapiens

Localization

Localization Comment Organism GeneOntology No. Textmining
chromatin 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 Homo sapiens 785
-
additional information the isozyme is not associated with chromatin during mitosis Homo sapiens
-
-

Natural Substrates/ Products (Substrates)

Natural Substrates Organism Comment (Nat. Sub.) Natural Products Comment (Nat. Pro.) Rev. Reac.
histone H3 N6,N6,N6-trimethyl-L-lysine26 + 2-oxoglutarate + O2 Homo sapiens
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histone H3 N6,N6-dimethyl-L-lysine26 + succinate + formaldehyde + CO2
-
?
histone H3 N6,N6,N6-trimethyl-L-lysine36 + 2-oxoglutarate + O2 Homo sapiens
-
histone H3 N6,N6-dimethyl-L-lysine36 + succinate + formaldehyde + CO2
-
?
histone H3 N6,N6,N6-trimethyl-L-lysine9 + 2-oxoglutarate + O2 Homo sapiens
-
histone H3 N6,N6-dimethyl-L-lysine9 + succinate + formaldehyde + CO2
-
?

Organism

Organism UniProt Comment Textmining
Homo sapiens O75164
-
-
Homo sapiens O94953
-
-
Homo sapiens Q6B0I6
-
-
Homo sapiens Q9H3R0
-
-

Source Tissue

Source Tissue Comment Organism Textmining
breast cancer cell
-
Homo sapiens
-
esophageal squamous cell carcinoma cell
-
Homo sapiens
-
gastric cancer cell line
-
Homo sapiens
-
medulloblastoma cell
-
Homo sapiens
-

Substrates and Products (Substrate)

Substrates Comment Substrates Organism Products Comment (Products) Rev. Reac.
histone H3 N6,N6,N6-trimethyl-L-lysine26 + 2-oxoglutarate + O2
-
Homo sapiens histone H3 N6,N6-dimethyl-L-lysine26 + succinate + formaldehyde + CO2
-
?
histone H3 N6,N6,N6-trimethyl-L-lysine36 + 2-oxoglutarate + O2
-
Homo sapiens histone H3 N6,N6-dimethyl-L-lysine36 + succinate + formaldehyde + CO2
-
?
histone H3 N6,N6,N6-trimethyl-L-lysine9 + 2-oxoglutarate + O2
-
Homo sapiens histone H3 N6,N6-dimethyl-L-lysine9 + succinate + formaldehyde + CO2
-
?

Subunits

Subunits Comment Organism
More enzyme domain structure includign JmjN, JmjC, PHD and Tudor domains, overview Homo sapiens
More enzyme domain structure including JmjN and JmjC domains, isozyme KDM4D lacks the PHD and Tudor domains, overview Homo sapiens
More enzyme domain structure including JmjN, JmjC, PHD and Tudor domains, overview Homo sapiens

Synonyms

Synonyms Comment Organism
GASC1
-
Homo sapiens
KDM4A
-
Homo sapiens
KDM4B
-
Homo sapiens
Kdm4c
-
Homo sapiens
KDM4D
-
Homo sapiens
lysine demethylase
-
Homo sapiens

General Information

General Information Comment Organism
evolution two families of lysine demethylases (KDM) are identified. The KDM4 family consists of four members: KDM4A, KDM4B, KDM4C and KDM4D Homo sapiens
malfunction dysregulated expression of KDM4A-D family promotes chromosomal instabilities Homo sapiens
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 Homo sapiens
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 Homo sapiens
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 Homo sapiens
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 Homo sapiens
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 Homo sapiens
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 Homo sapiens