SETDB1 Recombinant Protein

This gene encodes a histone methyltransferase which regulates histone methylation, gene silencing, and transcriptional repression. This gene has been identified as a target for treatment in Huntington Disease, given that gene silencing and transcription dysfunction likely play a role in the disease pathogenesis. Alternatively spliced transcript variants of this gene have been described.[provided by RefSeq, Jun 2011]

SETDB1: a protein lysine methyltransferase that specifically trimethylates K9 of histone H3 (H3K9me3), a specific tag for epigenetic transcriptional repression by recruiting HP1 (CBX1, CBX3 and/or CBX5) proteins to methylated histones. Unlike SUV39H H3K9 methyltransferase, which functions mainly in heterochromatin regions such as pericentric heterochromatin, SETDB1 functions mainly in euchromatic regions, playing a central role in the silencing of euchromatic genes. H3K9me3 is coordinated with DNA methylation. Interacts with a variety of proteins, including transcription factors (ERG), histone deacetylases (HDAC1/2), DNA methyltransferases (DNMT3A/B) and transcriptional co-repressors (mSin3A/B, MBD1, KAP-1, the ATFa-associated modulator mAM). Its activity is dependent on MBD1 and is heritably maintained through DNA replication by being recruited by CAF-1. Contains Tudor and methyl-CpG-binding domains, which may coordinate binding to methylated histones and methylated DNA, respectively. Is targeted to histone H3 by TIF1B, a factor recruited by KRAB zinc-finger proteins. Recruited by DNMT3A to silenced promoters in cancer cells. May play a role in the pathogenesis of Huntington's disease, since levels of SETDB1 and H3K9me3 are both increased in diseased brains. Belongs to the histone-lysine methyltransferase family. Suvar3-9 subfamily. Three isoforms of the human protein are produced by alternative splicing.

Protein type: Amino Acid Metabolism - lysine degradation; EC 2.1.1.43; Methyltransferase; Methyltransferase, protein lysine

Chromosomal Location of Human Ortholog: 1q21.3

Cellular Component: cytosol; intracellular membrane-bound organelle; nucleoplasm; nucleus; plasma membrane

Molecular Function: chromatin binding; protein binding

Biological Process: Ras protein signal transduction