SETD8

Entrez Summary: The protein encoded by this gene is a protein-lysine N-methyltransferase that can monomethylate Lys-20 of histone H4 to effect transcriptional repression of some genes. The encoded protein is required for cell proliferation and plays a role in chromatin condensation. [provided by RefSeq, May 2016].
UniProt Summary: Protein-lysine N-methyltransferase that monomethylates both histones and non-histone proteins. Specifically monomethylates 'Lys-20' of histone H4 (H4K20me1). H4K20me1 is enriched during mitosis and represents a specific tag for epigenetic transcriptional repression. 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. Nucleosomes are preferred as substrate compared to free histones. Mediates monomethylation of p53/TP53 at 'Lys-382', leading to repress p53/TP53-target genes. Plays a negative role in TGF-beta response regulation and a positive role in cell migration. {ECO:0000269|PubMed:12086618, ECO:0000269|PubMed:12121615, ECO:0000269|PubMed:15200950, ECO:0000269|PubMed:15933069, ECO:0000269|PubMed:15933070, ECO:0000269|PubMed:16517599, ECO:0000269|PubMed:17707234, ECO:0000269|PubMed:23478445}.

Pfam Domains GO Terms

Compound Hit Most Correlated Genes in Chemogenomics Tissues where Essential in the Avana Dataset (DepMap 20Q1)

Screen	Score
WYE-354 6μM R02 exp90	-2.33
RO-3307 4.7μM R02 exp80	-1.84
Epigallocatechin gallate 20μM R05 exp230	-1.7
2-Methoxyestradiol 0.2μM R01 exp40	1.77
GSK461364A 0.005μM R03 exp125	1.9

Global Fraction of Cell Lines Where Essential: 1/726

Tissue	Fraction Of Cell Lines Where Essential
1290807.0	0/1
909776.0	0/1
bile duct	0/28
blood	0/28
bone	0/25
breast	0/33
central nervous system	0/56
cervix	0/4
colorectal	0/17
esophagus	0/13
fibroblast	0/1
gastric	0/15
kidney	0/21
liver	0/20
lung	0/75
lymphocyte	0/14
ovary	0/26
pancreas	0/24
peripheral nervous system	0/16
plasma cell	0/15
prostate	0/1
skin	0/24
soft tissue	0/7
thyroid	0/2
upper aerodigestive	0/22
urinary tract	0/29
uterus	0/5

Expression Distribution

lysine N-methyltransferase activity
histone methyltransferase activity (H4-K20 specific)
histone H4-K20 methylation
peptidyl-lysine monomethylation
histone-lysine N-methyltransferase activity
protein-lysine N-methyltransferase activity
regulation of DNA damage response, signal transduction by p53 class mediator
p53 binding
histone lysine methylation
peptidyl-lysine methylation
histone methylation
chromosome
protein methylation
protein alkylation
regulation of signal transduction by p53 class mediator
regulation of response to DNA damage stimulus
transcription corepressor activity
macromolecule methylation
methylation
peptidyl-lysine modification
histone modification
covalent chromatin modification
cell division
chromatin organization
regulation of cellular response to stress
negative regulation of transcription by RNA polymerase II
peptidyl-amino acid modification
chromosome organization
negative regulation of transcription, DNA-templated
negative regulation of nucleic acid-templated transcription
negative regulation of RNA biosynthetic process
negative regulation of RNA metabolic process
cell cycle
negative regulation of cellular macromolecule biosynthetic process
negative regulation of nucleobase-containing compound metabolic process
negative regulation of macromolecule biosynthetic process
regulation of response to stress
negative regulation of cellular biosynthetic process
negative regulation of biosynthetic process
negative regulation of gene expression