SETD8 (PR-Set7)

SETD8 is protein-lysine N-methyltransferase that monomethylates both histones and non-histone proteins. SETD8 specifically monomethylates 'Lys-20' of histone H4 (H4K20me1). H4K20me1 is enriched during mitosis and represents a specific tag for epigenetic transcriptional repression. SETD8 mainly functions in euchromatin regions, thereby playing a central role in the silencing of euchromatic genes. SETD8 is required for cell proliferation, probably by contributing to the maintenance of proper higher order structure of DNA during mitosis. SETD8 is involved in chromosome condensation and proper cytokinesis. Nucleosomes are preferred as substrate compared to free histones. SETD8 mediates monomethylation of p53/TP53 at 'Lys-382', leading to repress p53/TP53-target genes.

SETD8 (PR-Set7) Related Areas

Enzyme>>Methyltransferase>>SETD8/PR-Set7

SETD8 (PR-Set7) Alternative Names

SETD8, PR-Set7, KMT5A, SET07, SET8 [Homo sapiens]

Setd8, PR-SET7, 2410195B05Rik, AA617402, AW536475, MGC117832 [Mus musculus]

Summaries for SETD8 (PR-Set7)

Wikipedia summary for SETD8 (PR-Set7):

Histone-lysine N-methyltransferase SETD8 is an enzyme that in humans is encoded by the SETD8 gene.

Human SETD8 (PR-Set7) Protein General Information

 

• Protein names: N-lysine methyltransferase SETD8
• Sequence length: 393 AA.
• Domain: Although the SET domain contains the active site of enzymatic activity, both sequences upstream and downstream of the SET domain are required for methyltransferase activity.
• Sequence similarities: Belongs to the histone-lysine methyltransferase family. PR/SET subfamily.
  Contains 1 SET domain.
• Catalytic activity: S-adenosyl-L-methionine + L-lysine-[histone] = S-adenosyl-L-homocysteine + N(6)-methyl-L-lysine-[histone].
• Subunit structure: Interacts with L3MBTL1.
• Subcellular location: Nucleus. Chromosome. Note: Specifically localizes to mitotic chromosomes. Associates with silent chromatin on euchromatic arms. Not associated with constitutive heterochromatin.
• Developmental stage: Not detected during G1 phase. First detected during S through G2 phases, and peaks during mitosis (at protein level).
• Induction: By HCFC1 C-terminal chain, independently of HCFC1 N-terminal chain.
• Caution: It is uncertain whether Met-1 or Met-72 is the initiator.
• Sequence caution: The sequence AAL40879.1 differs from that shown. Reason: Erroneous initiation. Translation N-terminally extended.

General information above from UniProt

Function for SETD8 (PR-Set7) Protein

UniProtKB:

SETD8 is protein-lysine N-methyltransferase that monomethylates both histones and non-histone proteins. SETD8 specifically monomethylates 'Lys-20' of histone H4 (H4K20me1). H4K20me1 is enriched during mitosis and represents a specific tag for epigenetic transcriptional repression. SETD8 mainly functions in euchromatin regions, thereby playing a central role in the silencing of euchromatic genes. SETD8 is required for cell proliferation, probably by contributing to the maintenance of proper higher order structure of DNA during mitosis. SETD8 is involved in chromosome condensation and proper cytokinesis. Nucleosomes are preferred as substrate compared to free histones. SETD8 mediates monomethylation of p53/TP53 at 'Lys-382', leading to repress p53/TP53-target genes.

Genatlas:

• SETD8 is monomethylase, consistent with its role in the maintenance of Lys-20 monomethylation during cell division
• SETD8 is methyltransferase that plays a novel role in regulating cell cycle by suppressing DNA replication through histone binding
• SETD8 can be a negative regulator of DNA replication and the destruction of SET8 is required for the onset of S phase
• SETD8 monomethylates Lys(20) of histone H4
• SETD8 has a function required for S phase progression and playing an important role in mammalian embryogenesis
• SETD8 plays an essential role for genomic stability in mammalian cells
• SETD8 monomethylates TP53 exclusively at lysine 382 (p53K382me1), and the placement of this modification negatively regulates TPp53 activity
• SETD8 is required for chromosome compaction in mitosis and for maintenance of genome integrity