SMYD5

Protein-lysine N-trimethyltransferase that specifically catalyzes trimethylation of 'Lys-22' of the RPL40/eL40 subunit of the 60S ribosome, thereby promoting translation elongation and protein synthesis. May also act as a histone methyltransferase in the context of histone octamers, but not on nucleosome substrates: trimethylates 'Lys-36' of histone H3 and 'Lys-20' of histone H4 to form H3K36me3 and H4K20me3, respectively (By similarity). The histone methyltransferase activity, which is independent of its SET domain, is however unsure in vivo. In association with the NCoR corepressor complex, involved in the repression of toll-like receptor 4 (TLR4)-target inflammatory genes in macrophages, possibly by catalyzing the formation of H4K20me3 at the gene promoters (By similarity). Plays an important role in embryonic stem (ES) cell self-renewal and differentiation (By similarity). Maintains genome stability of ES cells during differentiation through regulation of heterochromatin formation and repression of endogenous repetitive DNA elements by promoting H4K20me3 marks. Acts as a regulator of the hypothermia response: its degradation in response to mild hypothermia relieves the formation of H3K36me3 at gene promoters, allowing expression of the neuroprotective gene SP1 (By similarity)..

Function from UniProtKB (Q6GMV2), read 2026-09-23. CC BY 4.0.