Component of histone acetyltransferase complex responsible for the majority of histone H4 acetylation at lysine 16 which is implicated in the formation of higher-order chromatin structure. Acts as an E3 ubiquitin ligase that promotes monoubiquitination of histone H2B at 'Lys-35' (H2BK34Ub), but not that of H2A. This activity is greatly enhanced by heterodimerization with MSL1. H2B ubiquitination in turn stimulates histone H3 methylation at 'Lys-4' (H3K4me) and 'Lys-79' (H3K79me) and leads to gene activation, including that of HOXA9 and MEIS1. Component of a multisubunit histone acetyltransferase complex (MSL) at least composed of the KAT8/MOF/MYST1, MSL1/hampin, MSL2 and MSL3 (PubMed:16543150, PubMed:23084835). Forms a MSL heterotetrameric core with MSL1 (PubMed:16543150). Belongs to the MSL2 family. Extended N-terminus. Truncated N-terminus. Extended N-terminus.