EC Number   |
General Information |
Reference |
|---|
   2.1.1.366 | drug target |
downregulating SETDB1 is an attractive therapeutic option in AKT-driven cancer and for enhancing the immunotherapeutic response |
777166 |
| 2.1.1.366 | malfunction |
aberrant SETDB1 activity is linked to disease onset, including nervous, cardiovascular and gastrointestinal system disorders, as well as numerous inherited genetic syndromes. SETDB1 is most significantly involved in tumorigenesis by repressing tumor suppressor genes after establishing the H3K9me3 mark. SETDB1 activity results in higher aggressiveness and worse cancer prognosis and has therefore been regarded as an oncogene |
778396 |
| 2.1.1.366 | malfunction |
aberrant SETDB1 expression, and its oncogenic role is evident in many cancers. Amplified SETDB1 is associated with enhanced tumorigenesis and poor prognosis in a wide variety of cancers. This increased oncogenic effect is probably due to a SETDB1 methylation-associated suppressive effect on various tumor suppressors, AKT hyperactivation, and increased mutant p53 stability. SETDB1 overexpression shows a significant negative correlation with immunomodulatory outcomes through tumor immune evasion and IFN-I pathway repression |
777166 |
| 2.1.1.366 | metabolism |
CBX7 inhibition reduces H3K9 methylation levels. CBX7 inhibitors abolish the interaction between CBX7 and H3K9 methyltransferases and block both CBX7-and H3K9 methyltransferase-mediated gene repression |
777284 |
| 2.1.1.366 | more |
SETDB1 exists in three isoforms, with isoform 1 being considered as the canonical sequence, including all the necessary domains for full enzyme activity. Isoform 2 contains the same domains as isoform 1. Isoform 2 is produced by alternate splicing of an in-frame splice site which is present in the 3' coding region, resulting in C-terminal truncation in the post-SET domain, thus producing a shorter protein form. Isoform 3 lacks all the domains of the C-terminus that are required for enzyme activity |
778396 |
| 2.1.1.366 | physiological function |
ATFa-associated factor mAM stimulates ESET enzymatic activity by increasing the Vmax and decreasing the Km. mAM facilitates the ESET-dependent conversion of dimethyl H3-K9 to the trimethyl state both in vitro and in vivo. mAM enhances ESET-mediated transcriptional repression in a SAM-dependent manner, and this repression correlates with histone H3-K9 trimethylation at the promoter |
757646 |
| 2.1.1.366 | physiological function |
bivalend combinantion, dually marked histones H3K9me3/H3K14ac modification in the liver, is significantly decreased in old hepatocytes. A correlation between H3K9me3/H3K14ac bulk bivalent genomic regions and dually marked single nucleosomes is suggested. Histone H3K9 deacetylase Hdac3, as well as H3K9 methyltransferase Setdb1, found in complex Kap1, occupy both bulk and single nucleosome bivalent regions in both young and old livers, correlating to presence of H3K9me3. Expression of genes associated with bivalent regions in young liver, including those regulating cholesterol secretion and triglyceride synthesis, is upregulated in old liver once the bivalency is lost |
758617 |
| 2.1.1.366 | physiological function |
deletion of Setdb1 in Meckel's cartilage tissue leads to its enlargement. Chondrocytes from the Meckel's cartilage of Setdb1 conditional KO mice show increased size. At embryonic days 16.5 and 18.5, part of the perichondrium is disrupted and mineralization is observed in the Meckel's cartilage. Inhibition of Setdb1 causes increased proliferation in chondrocytes in the Meckel's cartilage as well as in siRNA-treated ATDC5 cells. Decreased expression of chondrogenic genes, such as Sox9, Mmp13, Collagen II, and Aggrecan, is observed as a result of Setdb1 inhibition in ATDC5 cells. SMAD-dependent BMP signaling is significantly increased by the loss of Setdb1 in both the Meckel's cartilage of Setdb1 conditional KO mice and siRNA-treated ATDC5 cells |
758727 |
| 2.1.1.366 | physiological function |
deletion of the catalytic domain of either histone methyltransferases EHMT2 or SETDB1 in growing oocytes leads to significant reduction of global H3K9me2 or H3K9me3 levels, respectively, in the maternal pronucleus. The asymmetry of global 5-methylcytosine (5mC) oxidation is significantly reduced in the zygotes that carry maternal mutation of either the Ehmt2 or Setdb1 genes. The levels of 5-hydroxymethylcytosine, 5-formylcytosine, and 5-carboxylcytosine increase, and 5mC levels decrease in the mutant maternal pronuclei. H3K9me3-rich rings around the nucleolar-like bodies retain 5mC in the maternal mutant zygotes. The maternal pronuclei expand in size in the mutant zygotes and contain a significantly increased number of nucleolar-like bodies compared with normal zygotes |
760074 |
| 2.1.1.366 | physiological function |
embryonic stem cells exhibit high expression of the ubiquitin-conjugating enzyme UBE2K. Loss of UBE2K upregulates the trimethyltransferase SETDB1, resulting in H3K9 trimethylation and repression of neurogenic genes during differentiation |
759079 |
