KMT5A
Developmental stage
Not detected during G1 phase. First detected during S through G2 phases, and peaks during mitosis (at protein level).
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.
Function
Protein-lysine N-methyltransferase that monomethylates both histones and non-histone proteins (PubMed:12086618, PubMed:12121615, PubMed:15964846, PubMed:17707234, PubMed:27338793). Specifically monomethylates 'Lys-20' of histone H4 (H4K20me1) (PubMed:12086618, PubMed:12121615, PubMed:15200950, PubMed:15933069, PubMed:15933070, PubMed:15964846, PubMed:16517599, PubMed:27338793). H4K20me1 is enriched during mitosis and represents a specific tag for epigenetic transcriptional repression (PubMed:12086618, PubMed:12121615, PubMed:15200950, PubMed:15933069, PubMed:15933070, PubMed:15964846, PubMed:16517599). Mainly functions in euchromatin regions, thereby playing a central role in the silencing of euchromatic genes (PubMed:12086618, PubMed:12121615, PubMed:15200950, PubMed:15933069, PubMed:15933070, PubMed:15964846, PubMed:16517599). Required for cell proliferation, probably by contributing to the maintenance of proper higher-order structure of DNA during mitosis (PubMed:12086618, PubMed:12121615, PubMed:15200950, PubMed:15933069, PubMed:15933070, PubMed:15964846, PubMed:16517599). Involved in chromosome condensation and proper cytokinesis (PubMed:12086618, PubMed:12121615, PubMed:15200950, PubMed:15933069, PubMed:15933070, PubMed:15964846, PubMed:16517599). Nucleosomes are preferred as substrate compared to free histones (PubMed:12086618, PubMed:12121615, PubMed:15200950, PubMed:15933069, PubMed:15933070, PubMed:15964846, PubMed:16517599). Mediates monomethylation of p53/TP53 at 'Lys-382', leading to repress p53/TP53-target genes (PubMed:17707234). Plays a negative role in TGF-beta response regulation and a positive role in cell migration (PubMed:23478445).
Post-translational modifications
Acetylated at Lys-162; does not affect methyltransferase activity. Deacetylated at Lys-162 possibly by SIRT2; does not change methyltransferase activity.
Ubiquitinated and degraded by the DCX(DTL) complex.
Sequence Similarities
Belongs to the class V-like SAM-binding methyltransferase superfamily. Histone-lysine methyltransferase family. PR/SET subfamily.
Cellular localization
- Nucleus
- Chromosome
- Specifically localizes to mitotic chromosomes (PubMed:12208845). Colocalized with SIRT2 at mitotic foci (PubMed:23468428). Associates with chromosomes during mitosis; association is increased in a H(2)O(2)-induced oxidative stress-dependent manner (PubMed:23468428). Associates with silent chromatin on euchromatic arms (PubMed:12086618). Not associated with constitutive heterochromatin (PubMed:12086618).
Alternative names
PRSET7, SET07, SET8, SETD8, KMT5A, N-lysine methyltransferase KMT5A, H4-K20-HMTase KMT5A, Histone-lysine N-methyltransferase KMT5A, Lysine N-methyltransferase 5A, Lysine-specific methylase 5A, PR/SET domain-containing protein 07, SET domain-containing protein 8, PR-Set7, PR/SET07