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SETD8 a protein-lysine N-methyltransferase that monomethylates both histones and non-histone proteins. Methylates K20 of histone H4 (H4K20me1), a specific tag for epigenetic transcriptional repression. SETD8 protein and H4K20me1 levels are cell cycle regulated, both increasing in S phase and peaking at G2/M phase. Interacts with the PCNA protein, associates with sites of active DNA synthesis and is required for DNA replication and genome stability during S phase. Inhibition of SET8 using shRNA results in arrest of replication forks, induction of double-stranded DNA breaks and a Chk1-mediated cell-cycle arrest in S and G2/M phases of the cell cycle. Mainly functions in euchromatin regions, thereby playing a central role in the silencing of euchromatic genes. Required for cell proliferation, probably by contributing to the maintenance of proper higher order structure of DNA during mitosis. Involved in chromosome condensation and proper cytokinesis. Inhibition of SET8 using shRNA results in arrest of replication forks, induction of double-stranded DNA breaks and a Chk1-mediated cell-cycle arrest in S and G2/M phases of the cell cycle. Nucleosomes are preferred as substrate compared to free histones. Methylates p53K382, leading to repression of the pro-apoptotic and checkpoint activation functions of p53. SET8 expression levels decrease in response to DNA damage, allowing p53 to activate checkpoints and/or apoptosis. Both the methylation of histone H4K20 and p53K382 appear to be important for the functions of SET8 in S phase. Belongs to the histone-lysine methyltransferase family. PR/SET subfamily. Two isoforms of the human protein are produced by alternative splicing. Note: This description may include information from UniProtKB.
Protein type: Amino Acid Metabolism - lysine degradation; EC; Methyltransferase; Methyltransferase, protein lysine
Chromosomal Location of Human Ortholog: 12q24.31
Cellular Component: cytosol; nucleoplasm; nucleus
Molecular Function: histone lysine N-methyltransferase activity (H4-K20 specific); histone-lysine N-methyltransferase activity; lysine N-methyltransferase activity; p53 binding; protein binding; protein-lysine N-methyltransferase activity; transcription corepressor activity
Biological Process: negative regulation of transcription from RNA polymerase II promoter; negative regulation of transcription, DNA-dependent; peptidyl-lysine mono-methylation; regulation of DNA damage response, signal transduction by p53 class mediator
Reference #:  Q9NQR1 (UniProtKB)
Alt. Names/Synonyms: H4-K20-HMTase SETD8; H4-K20-specific histone methyltransferase; Histone-lysine N-methyltransferase SETD8; KMT5A; Lysine N-methyltransferase 5A; PR-Set7; PR/SET domain containing protein 8; PR/SET domain-containing protein 07; PR/SET07; PRSET7; SET domain containing (lysine methyltransferase) 8; SET domain-containing protein 8; SET07; SET8; SETD8
Gene Symbols: KMT5A
Molecular weight: 42,890 Da
Basal Isoelectric point: 9.69  Predict pI for various phosphorylation states
CST Pathways:  Histone Methylation
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