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FLASH GENE

Symbol

SETD8

contributors: mct/npt/pgu - updated : 23-03-2017

HGNC name	SET domain containing (lysine methyltransferase) 8
HGNC id	29489

FLASH GENE DNA RNA EXPRESSION PROTEIN DISORDER ANIMAL & CELL MODELS

RNA

TRANSCRIPTS	type	messenger

identification nb exons type bp product Protein kDa AA specific expression Year Pubmed SETD8 8 - 2765 - 352 - 2008 18418072

EXPRESSION

Type

expressed in	(based on citations)
organ(s)	System Organ level 1 Organ level 2 Organ level 3 Organ level 4 Level Pubmed Species Stage Rna symbol Reproductive male system testis       Homo sapiens

cells

System Cell Pubmed Species Stage Rna symbol Blood/Hematopoietic erythroid Homo sapiens Reproductive spermatogonia Homo sapiens

cell lineage

cell lines

fluid/secretion

at STAGE

PROTEIN

PHYSICAL PROPERTIES

STRUCTURE

motifs/domains	a SET domain
	a histone-binding domain
	a long recognition sequence motif covering seven amino acid

HOMOLOGY

Homologene

FAMILY	histone-lysine methyltransferase family
	PR/SET subfamily

CATEGORY

enzyme

SUBCELLULAR LOCALIZATION	intracellular
	intracellular,nucleus,chromatin/chromosome
text	concentrated in the nucleus during G(1) and G(2) phases, and was excluded from the nucleus during S phase
	undetectable during S phase and instead is detected during late G2, mitosis, and early G1

basic FUNCTION	monomethylase, consistent with its role in the maintenance of Lys-20 monomethylation during cell division
	methyltransferase that plays a novel role in regulating cell cycle by suppressing DNA replication through histone binding
	can be a negative regulator of DNA replication and the destruction of SET8 is required for the onset of S phase
	monomethylate Lys(20) of histone H4
	having a function required for S phase progression and playing an important role in mammalian embryogenesis
	playing an essential role for genomic stability in mammalian cells
	positively regulates the expression of PPARG and its targets through H4K20 monomethylation
	monomethylates TP53 exclusively at lysine 382 (p53K382me1), and the placement of this modification negatively regulates TPp53 activity
	required for chromosome compaction in mitosis and for maintenance of genome integrity
	the turnover of SETD8 is accelerated after ultraviolet irradiation dependent on the DTL ubiquitin ligase and PCNA
	acts as a dual epigenetic modifier on the promoters of the TWIST1 target genes CDH1 and CDH2 via its H4K20 monomethylation activity
	crucial inhibitor of apoptosis in skin and its activity is essential for epidermal stem cell survival, proliferation and differentiation
	histone lysine methyltransferase, which monomethylates the histone 4 lysine 20 AA, playing important roles in cell cycle control and genomic stability
	required for proper cell cycle progression and is subject to degradation by the DTL ubiquitin ligase complex as a function of the cell cycle and DNA damage
	is the sole histone methyltransferase in mammals capable of monomethylating histone H4 lysine 20 (H4K20me1)
	has likely an erythroid-cell-specific function
	STRA8 and SETD8 display a cell cycle-dependent expression pattern in germline cells.

CELLULAR PROCESS

nucleotide, chromatin organization, methylation

PHYSIOLOGICAL PROCESS

development

PATHWAY

metabolism

signaling

a component

INTERACTION

DNA	associated with silent chromatin

RNA

small molecule

protein	binds to the H4 N-terminal tail (H4NT) and blocks the acetylation of lysine residues K5, K8 and K12 of histone H4 during G(1)
	interacts with proliferating cell nuclear antigen through a conserved motif, and is required for DNA replication fork progression
	interacting with L3MBTL and HIST4H4 (importance of HIST4H4 monomethylation and of SETD8 for L3MBTL function)
	DTL-dependent destruction of SETD8 in S phase preserves genome stability by preventing aberrant chromatin compaction during DNA synthesis
	during the DNA damage response, interaction with PCNA through a specialized "PIP degron" domain targets it for PCNA-coupled DTL-dependent proteolysis
	targeted for degradation during S phase by the DTL ubiquitin ligase in a proliferating cell nuclear antigen (PCNA)-dependent manner
	SETD8 interacts with the UBE2I E2 SUMO conjugating enzyme (directly binds SETD8 proximal to the catalytic SET domain)
	physically associated with TWIST1, a master regulator of epithelial-mesenchymal transition (EMT)
	regulates the function of proliferating cell nuclear antigen (PCNA) protein through lysine methylation
	is an important regulator of erythroid maturation that works in part through repression of GATA2 expression
	SETD8 negatively regulated transcriptional activity of the STRA8 promoter

cell & other

REGULATION

activated by

PPARG during adipogenesis

ASSOCIATED DISORDERS

ANIMAL & CELL MODELS