EC Number   |
General Information |
Reference  |
|---|
   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 | physiological function |
SETDB1 methylation regulates H3K9me3 in the OTX2 promoter region and inhibits the expression of OTX2. SETDB1 expression is downregulated in osteoporotic femoral tissues and is involved in osteogenic differentiation. Upregulation of SETDB1 promotes osteogenic differentiation by inhibiting OTX2 and activating the BMP-Smad and Wnt/beta-catenin pathways in osteoporosis |
777586 |
| 2.1.1.366 | physiological function |
the cytoplasmic fraction of the histone lysine methyltransferase Setdb1 is essential for survival of embryonic stem cells. Setdb1 interacts with many RNA-binding proteins and translation regulators such as Trim71. Setdb1 is required for Trim71 complex integrity cSetdb1 regulates the abundance of specific mRNAs, of which Trim71 and hnRNPc targets |
777831 |
| 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 | 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 |
SETDB1 has a central role in normal physiology and nervous system development, having been implicated in the regulation of cell cycle progression, inactivation of the X chromosome, immune cells function, expression of retroelements and formation of promyelocytic leukemia nuclear bodies. SETDB1 has been frequently deregulated in carcinogenesis, being implicated in the pathogenesis of gliomas, melanomas, as well as in lung, breast, gastrointestinal and ovarian tumors, where it mainly exerts an oncogenic role |
778396 |
| 2.1.1.366 | physiological function |
the enzyme is involved in heterochromatin formation and silencing of repeat elements |
778808 |
| 2.1.1.366 | physiological function |
SETDB1 strengthens non-small cell lung cancer cell migratory and invasive abilities by promoting invadopodia formation and extracellular matrix degradation. At the molecular level, SETDB1 suppresses the expression of FOXA2, a crucial tumor and metastasis suppressor via coordinated epigenetic mechanisms. SETDB1 not only catalyzes histone H3K9 methylation on FOXA2 genomic locus, but also recruits DNMT3A to regulate DNA methylation on CpG island. Setdb1 is essential for malignant progression and metastasis of murine lung adenocarcinoma |
778826 |
| 2.1.1.366 | physiological function |
histone methyltransferase SETDB1 safeguards mouse fetal hematopoiesis by suppressing activation of cryptic enhancers maintaining the proper balance and differentiation of mouse fetal liver hematopoietic stem and progenitor cells |
779191 |
