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. L-lysyl(20)-[histone H4] + S-adenosyl-L-methionine = H(+) + N(6)-methyl-L-lysyl(20)-[histone H4] + S-adenosyl-L-homocysteine L-lysyl-[protein] + S-adenosyl-L-methionine = H(+) + N(6)-methyl-L-lysyl-[protein] + S-adenosyl-L-homocysteine Interacts with L3MBTL1. Interacts with SIRT2 (phosphorylated form); the interaction is direct, stimulates KMT5A-mediated methyltransferase activity at histone H4 'Lys-20' (H4K20me1) and is increased in a H(2)O(2)-induced oxidative stress-dependent manner (By similarity). Specifically localizes to mitotic chromosomes. Associates with silent chromatin on euchromatic arms. Colocalized with SIRT2 at mitotic foci. Associates with chromosomes during mitosis; association is increased in a H(2)O(2)-induced oxidative stress-dependent manner. Not associated with constitutive heterochromatin (By similarity). 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. Acetylated at Lys-131; does not change methyltransferase activity. Deacetylated at Lys-131 by SIRT2; does not change methyltransferase activity (By similarity). Ubiquitinated and degraded by the DCX(DTL) complex. Belongs to the class V-like SAM-binding methyltransferase superfamily. Histone-lysine methyltransferase family. PR/SET subfamily.