Histone methyltransferase that specifically methylates monomethylated 'Lys-20' (H4K20me1) and dimethylated 'Lys-20' (H4K20me2) of histone H4 to produce respectively dimethylated 'Lys-20' (H4K20me2) and trimethylated 'Lys-20' (H4K20me3) and thus regulates transcription and maintenance of genome integrity. In vitro also methylates unmodified 'Lys-20' (H4K20me0) of histone H4 and nucleosomes (By similarity). H4 'Lys-20' trimethylation represents a specific tag for epigenetic transcriptional repression. Mainly functions in pericentric heterochromatin regions, thereby playing a central role in the establishment of constitutive heterochromatin in these regions. KMT5B is targeted to histone H3 via its interaction with RB1 family proteins (RB1, RBL1 and RBL2) (By similarity). Plays a role in myogenesis by regulating the expression of target genes, such as EID3. Facilitates TP53BP1 foci formation upon DNA damage and proficient non-homologous end-joining (NHEJ)-directed DNA repair by catalyzing the di- and trimethylation of 'Lys-20' of histone H4 (By similarity). May play a role in class switch reconbination by catalyzing the di- and trimethylation of 'Lys-20' of histone H4 (By similarity). N(6)-methyl-L-lysyl(20)-[histone H4] + S-adenosyl-L-methionine = H(+) + N(6),N(6)-dimethyl-L-lysyl(20)-[histone H4] + S-adenosyl-L-homocysteine N(6),N(6)-dimethyl-L-lysyl(20)-[histone H4] + S-adenosyl-L-methionine = H(+) + N(6),N(6),N(6)-trimethyl-L-lysyl(20)-[histone H4] + S-adenosyl-L-homocysteine L-lysyl(20)-[histone H4] + S-adenosyl-L-methionine = H(+) + N(6)-methyl-L-lysyl(20)-[histone H4] + S-adenosyl-L-homocysteine Inhibited by 6,7-Dichloro-N-cyclopentyl-4-(pyridin-4-yl)phthalazin-1-amine (A-196). A-196 is competitive with the histone peptide substrate H4K20me1 but non competitive with S-adenosyl-L-methionine. Homodimer (By similarity). Interacts with HP1 proteins CBX1, CBX3 and CBX5. Interacts with RB1 family proteins RB1, RBL1 and RBL2 (By similarity). Interacts (via C-terminus) with FRG1 (By similarity). Associated with pericentric heterochromatin. CBX1 and CBX5 are required for the localization to pericentric heterochromatin (By similarity). Belongs to the class V-like SAM-binding methyltransferase superfamily. Histone-lysine methyltransferase family. Suvar4-20 subfamily.