Recombinant Human SETDB1 (KMT1E) Protein

Name: Recombinant Human SETDB1 (KMT1E) Protein
Brand: Beta LifeScience
SKU: BL-1196SG
Availability: InStock

Collections: High-quality recombinant proteins, Other recombinant proteins

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Product Overview

Tag	GST
Host Species	Human
Accession	BC028671
Synonym	KMT1E, ESET, KG1T, KIAA0067
Background	Histone-lysine N-methyltransferase SETDB1 (SETD6) specifically trimethylates 'Lys-9' of histone H3 and plays a central role in the silencing of euchromatic genes. SETDB1 is targeted to histone H3 by TRIM28/TIF1B, a factor recruited by KRAB zinc-finger proteins. Required for activated KRAS-mediated promoter hypermethylation and transcriptional silencing of tumor suppressor genes (TSGs) or other tumor-related genes in colorectal cancer (CRC) cells by forming a corepressor complex. It was also found to be responsible for transcriptionally repressive state of genes in embryonic stem cells (ESCs).
Description	Recombinant human SETDB1 (KMT1E) (715-end) was produced by Baculovirus in Sf9 insect cells, fused with a GST tag at N-terminus. This protein is purified with our unique purification methods.
Source	Sf9 insect cells
AA Sequence	715a.a.-end
Molecular Weight	~100 kDa
Purity	For specific purity information on a given lot, see related COA.
Endotoxin	< 1.0 EU per μg of the protein as determined by the LAL method
Formulation	Recombinant protein is supplied in 50mM Tris-HCl, pH 7.5, 50mM NaCl, 10mM Glutathione, 0.25mM DTT, 0.1mM EDTA, 0.1mM PMSF and 25% glycerol.
Stability	The recombinant protein is stable for up to 12 months at -70°C
Usage	For Research Use Only
Storage	Recombinant Human SETDB1 (KMT1E) Protein should be stored should be stored at < -70°C. It is recommended that the protein be aliquoted for optimal storage. Avoid repeated freeze-thaw cycles.

Target Details

Target Function	Histone methyltransferase that specifically trimethylates 'Lys-9' of histone H3. H3 'Lys-9' trimethylation represents a specific tag for epigenetic transcriptional repression by recruiting HP1 (CBX1, CBX3 and/or CBX5) proteins to methylated histones. Mainly functions in euchromatin regions, thereby playing a central role in the silencing of euchromatic genes. H3 'Lys-9' trimethylation is coordinated with DNA methylation. Required for HUSH-mediated heterochromatin formation and gene silencing. Forms a complex with MBD1 and ATF7IP that represses transcription and couples DNA methylation and histone 'Lys-9' trimethylation. Its activity is dependent on MBD1 and is heritably maintained through DNA replication by being recruited by CAF-1. SETDB1 is targeted to histone H3 by TRIM28/TIF1B, a factor recruited by KRAB zinc-finger proteins. Probably forms a corepressor complex required for activated KRAS-mediated promoter hypermethylation and transcriptional silencing of tumor suppressor genes (TSGs) or other tumor-related genes in colorectal cancer (CRC) cells. Required to maintain a transcriptionally repressive state of genes in undifferentiated embryonic stem cells (ESCs). In ESCs, in collaboration with TRIM28, is also required for H3K9me3 and silencing of endogenous and introduced retroviruses in a DNA-methylation independent-pathway. Associates at promoter regions of tumor suppressor genes (TSGs) leading to their gene silencing. The SETDB1-TRIM28-ZNF274 complex may play a role in recruiting ATRX to the 3'-exons of zinc-finger coding genes with atypical chromatin signatures to establish or maintain/protect H3K9me3 at these transcriptionally active regions.
Subcellular Location	Nucleus. Cytoplasm. Chromosome.
Protein Families	Class V-like SAM-binding methyltransferase superfamily, Histone-lysine methyltransferase family, Suvar3-9 subfamily
Database References	HGNC: 10761 OMIM: 604396 KEGG: hsa:9869 STRING: 9606.ENSP00000271640 UniGene: Hs.643565
Tissue Specificity	Widely expressed. High expression in testis.

Gene Functions References

Study in hepatocellular carcinoma (HCC) cells proves that SETDB1 promotes the proliferation and migration of cells by forming SETDB1-Tiam1 compounds. SETDB1-Tiam1 compounds were involved in a novel pathway, which regulated epigenetic modification of gene expression in HCC patients samples. PMID: 29739365
SETDB1 loss results in decompaction of the Xi chromosome partly through reactivation of an enhancer in the IL1RAPL1 gene. PMID: 30103804
SETDB1 knockdown might suppress breast cancer progression at least partly by miR-381-3p-related regulation, providing a novel prospect in breast cancer therapy. PMID: 30309377
Enhancer of Zeste Homolog 2 (EZH2), SET domain, bifurcated 1 protein (SETDB1), lysine-specific histone demethylase 1 (LSD1), histone H3 methylation (H3K9me3 and H3K27me3) expression are altered in colorectal cancer (CRC) and may play a role in colorectal carcinogenesis. PMID: 30105513
Increased expression of SETDB1 may predict poor overall survival. PMID: 29901162
SETDB1 is enriched at H3K9me3 regions and K9me3/K14ac is enriched at SETDB1 binding sites overlapping with LINE elements, suggesting that recruitment of the SETDB1 complex to K14ac/K9me regions has a role in silencing of active genomic regions. PMID: 29234025
these data identify a critical functional role for ATF7IP in heterochromatin formation by regulating SETDB1 abundance in the nucleus. PMID: 27732843
SETDB1 triggers silencing of retrotransposons to inhibit the interferon response in acute myeloid leukemia cells. PMID: 28887438
analysis of a 1q21.3 deletion encompassing SETDB1 that provides further support for the role of chromatin modifiers in the etiology of autism spectrum disorder PMID: 27119313
SETDB1 protein expression was significantly associated with poor survival and was related to TNM stage. PMID: 28913972
SETDB1, a major histone H3K9 methyltransferase is monoubiquitinated at the evolutionarily conserved lysine-867 in its SET-Insertion domain. This ubiquitination is directly catalyzed by UBE2E family of E2 enzymes in an E3-independent manner while the conjugated-ubiquitin (Ub) is protected from active deubiquitination. PMID: 27237050
These results suggest that the ubiquitination of SETDB1 at lysine 867 controls the expression of its target gene by activating its H3K9 methyltransferase activity. PMID: 27798683
Authors observed several complementary mechanisms contributing to the upregulation of SETDB1 in HCC cells. Besides copy number gains at the SETDB1 gene locus at chromosome 1q21 enhanced SETDB1 transcription mediated by the transcription factor SP1 could be detected. PMID: 27164857
BRCA1 and SETDB1 stand out as the most significant prognostic markers in this group of patients PMID: 26542178
These results suggest that SETDB1- mediated FosB expression is a common molecular phenomenon, and might be a novel pathway responsible for the increase in cell proliferation that frequently occurs during anticancer drug therapy. PMID: 26949019
SETDB1 mutations are associated with malignant pleural mesotheliomas. PMID: 26824986
Upon HBV infection, cellular mechanisms involving SETDB1-mediated H3K9me3 and HP1 induce silencing of HBV cccDNA transcription through modulation of chromatin structure. PMID: 26143443
The SETDB1 protein was closely associated with the prognosis of prostate cancer (PCa). Bioinformatics suggested that SETDB1 might promote PCa bone metastasis through the WNT pathway. In conclusion, SETDB1 might be associated with the development of bone metastases from PCa PMID: 26846621
results indicate that ATF7IP does not directly modulate SETDB1 catalytic activity, suggesting alternate roles, such as affecting cellular localization or mediating interaction with additional binding partners. PMID: 26813693
SETDB1 is an oncogene that is frequently up-regulated in human HCCs; the multiplicity of SETDB1 activating mechanisms at the chromosomal, transcriptional, and posttranscriptional levels together facilitates SETDB1 up-regulation in human HCC PMID: 26481868
regulates cancer cell growth via methylation of p53 PMID: 26471002
SETDB1, localized in the nucleus, might undergo degradation by the proteasome and be exported to the cytosol, resulting in its detection mainly in the cytosol. PMID: 26296461
Exogenous expression of MyoD reversed transcriptional repression of MyoD promoter-driven lucif-erase reporter by Setdb1 shRNA and rescued myogenic differentiation of C2C12 myoblast cells depleted of endogenous Setdb1. PMID: 25715926
Authors demonstrate that a KMT1E-containing complex directly interacts with the FcgammaRIIb promoter and that histone H3 at lysine 9 tri-methylation at this promoter is dependent on Setdb1 PMID: 25569264
MiR-7, inhibited indirectly by lincRNA HOTAIR, directly inhibits SETDB1 and reverses the Epithelial-mesenchymal transition of breast cancer stem cells by down regulating the STAT3 pathway PMID: 25070049
Report elevated levels of SETDB1 in non-small lung cancers, associated with neoplasm grading and tumor growth. PMID: 25404354
This observation suggests that the ZNF274/SETDB1 complex bound to the SNORD116 cluster may protect the Prader-Willi syndrome induced pluripotent cells from DNA demethylation during early development. PMID: 24760766
Together, our findings defined an essential role for the KMT1E/SMAD2/3 repressor complex in TGFbeta-mediated lung cancer metastasis. PMID: 25477335
SETDB1 is associated with frequent methylation of the euchromatic p16(INK) (4A) promoter and several prognostic parameters in melanomas PMID: 24673285
data suggested that SETDB1 is overexpressed in human PCa. Silencing SETDB1 inhibited PCa cell proliferation, migration and invasion PMID: 24556744
overexpression of SETDB1 or LSD1 had no prognostic impact in patients with melanoma PMID: 24658378
SETDB1 expression was upregulated in glioma cell lines and in glioma tissues compared to normal brain, being positively correlated with grade and histological malignancy. PMID: 23943221
SETDB1 is a bona fide oncogene undergoing gene amplification-associated activation in lung cancer. PMID: 23770855
of ESET plays an essential role in the maintenance of articular cartilage by preventing articular chondrocytes from terminal differentiation and may have implications in joint diseases such as osteoarthritis. PMID: 24056368
A transgenic Setdb1 model established a link between this gene and behavior. PMID: 23055267
analysis of a KRAB domain-containing ZNF (ZNF274) that is involved in recruitment of the KAP1 and SETDB1 to specific regions of the human genome PMID: 21170338
studies establish SETDB1 as an oncogene in melanoma and underscore the role of chromatin factors in regulating tumorigenesis PMID: 21430779
Contributes to HP1-mediated silencing of euchromatic genes by KRAB zinc-finger proteins; KAP-1, SETDB1, H3-MeK9, and HP1 are enriched at promoter sequences of a euchromatic gene silenced by the KRAB-KAP-1 repression system PMID: 11959841
mAM/hAM facilitates conversion of H3-K9 dimethyl to trimethyl by ESET/SETDB1 PMID: 14536086
Data show that the methyl-CpG binding protein MBD1 forms a stable complex with histone H3-K9 methylase SETDB1. PMID: 15327775
These data suggest that MBD1.MCAF1.SETDB1 complex facilitates the formation of heterochromatic domains, emphasizing the role of MCAF/AM family proteins in epigenetic control, and describe a new family member, MCAF2 (ATF7IP2). PMID: 15691849
histone methyltransferase SETDB1 and the DNA methyltransferase DNMT3A interact directly and localize to promoters silenced in cancer cells PMID: 16682412
modulation of gene silencing mechanisms, through regulation of the ESET gene is important to neuronal survival and, as such, may be a promising treatment in Huntington's disease patients PMID: 17142323
Akt/PKB interacts with the histone H3 methyltransferase SETDB1 and coordinates to silence gene expression. PMID: 17577629
SETDB1 can specifically methylate HIV-1 Tat preferentially at lysine 51. PMID: 18498648

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