Cloned (Comment) | Organism |
---|---|
gene KDM4A, recombinant expression of EGFP-tagged full-length and truncated enzymes versions in U2-O2 cells | 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, and mutant enzymes versions | Homo sapiens |
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, construction of diverse chimeric enzyme mutants, overview. 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, construction of diverse chimeric enzyme mutants, overview. 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 | 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 | while KDM4C is associated with mitotic chromatin, KDM4A-B proteins are excluded from chromatin throughout prometaphase-telophase | Homo sapiens | - |
- |
Natural Substrates | Organism | Comment (Nat. Sub.) | Natural Products | Comment (Nat. Pro.) | Rev. | Reac. |
---|---|---|---|---|---|---|
[histone H3]-N6,N6,N6-trimethyl-L-lysine 26 + 2-oxoglutarate + O2 | Homo sapiens | - |
[histone H3]-N6,N6-dimethyl-L-lysine 26 + succinate + formaldehyde + CO2 | - |
? | |
[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 | UniProt | Comment | Textmining |
---|---|---|---|
Homo sapiens | O75164 | - |
- |
Homo sapiens | O94953 | - |
- |
Homo sapiens | Q9H3R0 | - |
- |
Source Tissue | Comment | Organism | Textmining |
---|---|---|---|
carcinoma cell | - |
Homo sapiens | - |
U2-OS cell | - |
Homo sapiens | - |
Substrates | Comment Substrates | Organism | Products | Comment (Products) | Rev. | Reac. |
---|---|---|---|---|---|---|
additional information | the bifunctional enzyme is active on H3K9me3/me2 (EC 1.14.11.66) and H3K36me3/me2 substrates | Homo sapiens | ? | - |
? | |
[histone H3]-N6,N6,N6-trimethyl-L-lysine 26 + 2-oxoglutarate + O2 | - |
Homo sapiens | [histone H3]-N6,N6-dimethyl-L-lysine 26 + succinate + formaldehyde + CO2 | - |
? | |
[histone H3]-N6,N6,N6-trimethyl-L-lysine 26 + 2-oxoglutarate + O2 | - |
Homo sapiens | [histone H3]-N6,N6-dimethyl-L-lysine26 + succinate + formaldehyde + CO2 | - |
? | |
[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 | Comment | Organism |
---|---|---|
KDM4A | - |
Homo sapiens |
KDM4B | - |
Homo sapiens |
Kdm4c | - |
Homo sapiens |
More | see also EC 1.14.11.66 | Homo sapiens |
General Information | Comment | Organism |
---|---|---|
evolution | the human KDM4 family consists of four members, KDM4A-D (also known as JMJD2A-D). These enzymes specifically catalyze the demethylation of H3K9me3/me2, H3K36me2/me3 and H1.4K26me2/me3 in a Fe2+ and 2-oxoglutarate-dependent manner. Besides the catalytic JmjC domain, KDM4 demethylases contain the JmjN domain, which is also required for the demethylase activity. In addition, all KDM4 members, except the shortest KDM4D protein, contain two Plant homeodomain (PHD) and two Tudor domains. Gene KDM4D is Y chromosome-encoded and a truncated enzyme variant compared to KDM4A-C | Homo sapiens |
evolution | the human KDM4 family consists of four members, KDM4A-D (also known as JMJD2A-D). These enzymes specifically catalyze the demethylation of H3K9me3/me2, H3K36me2/me3 and H1.4K26me2/me3 in a Fe2+ and 2-oxoglutarate-dependent manner. Besides the catalytic JmjC domain, KDM4 demethylases contain the JmjN domain, which is also required for the demethylase activity. In addition, all KDM4 members, except the shortest KDM4D protein, contain two Plant homeodomain (PHD) and two Tudor domains. PHD and Tudor domains are not required for KDM4 enzymatic activity. Gene KDM4D is Y chromosome-encoded and a truncated enzyme variant compared to KDM4A-C | Homo sapiens |
malfunction | dysregulated expression of KDM4A-D family promotes chromosomal instabilities | Homo sapiens |
malfunction | dysregulated expression of KDM4A-D family promotes chromosomal instabilities. Dysregulation of KDM4C expression promotes mitotic chromosome missegregation. KDM4B-C members are overexpressed in several types of human cancer and its depletion impairs cancer cell proliferation | Homo sapiens |
malfunction | dysregulated expression of KDM4A-D family promotes chromosomal instabilities. KDM4B-C members are overexpressed in several types of human cancer and its depletion impairs cancer cell proliferation | Homo sapiens |
physiological function | various types of human cancers exhibit amplification or deletion of KDM4A-D members, which selectively demethylate H3K9 and H3K36, thus implicating their activity in promoting carcinogenesis | Homo sapiens |