SETD4

Protein-lysine N-methyltransferase that methylates both histones and non-histone proteins. Via its catalytic activity, regulates many processes, including cell proliferation, cell differentiation, inflammatory response and apoptosis. Regulates the inflammatory response by mediating mono- and dimethylation of 'Lys-4' of histone H3 (H3K4me1 and H3K4me2, respectively), leading to activate the transcription of pro-inflammatory cytokines IL6 and TNF (By similarity). Through the catalysis of TBK1 monomethylation, may regulate virus-induced interferon signaling. TBK1 monomethylation enhances its interaction with MAVS, STING and IRF3, hence promoting antiviral interferon signaling. Also involved in the regulation of stem cell quiescence by catalyzing the trimethylation of 'Lys-20' of histone H4 (H4K20me3), thereby promoting heterochromatin formation. In the brain, epigenetically controls quiescence of neural stem cells for sustaining a protected neural stem cell population and maintaining a stem cell reservoir for neurogenesis (By similarity). Involved in proliferation, migration, paracrine and myogenic differentiation of bone marrow mesenchymal stem cells (BMSCs) (By similarity). Through the catalysis of XRCC5/Ku70 trimethylation, regulates BAX-mediated apoptosis. SETD4-catalyzed XRCC5 methylation results in XRCC5 translocation to the cytoplasm, where it interacts with BAX, sequestering it from the mitochondria, hence preventing BAX-mediated apoptosis..

Function from UniProtKB (Q9NVD3), read 2026-09-23. CC BY 4.0.