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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
EXPRESSION
Type
   expressed in (based on citations)
organ(s)
SystemOrgan level 1Organ level 2Organ level 3Organ level 4LevelPubmedSpeciesStageRna symbol
Reproductivemale systemtestis    Homo sapiens
cells
SystemCellPubmedSpeciesStageRna symbol
Blood/Hematopoieticerythroid Homo sapiens
Reproductivespermatogonia 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