In mammalian cells, PRMT5 is tightly bound by WDR77 (MEP50). This interaction is required for PRMT5 activity (Friesen et al. 2002). The structure of PRMT5 and WDR77 (MEP50) was determined, bound to an S-adenosylmethionine analog and a peptide substrate derived from histone H4. The structure reveals a hetero-octameric complex formation, with close interaction between the seven-bladed beta-propeller WDR77 (MEP50) and the N-terminal domain of human PRMT5 (Antonysamy et al. 2012, Ho et al. 2013)
JAK2 mutation V617F casues JAK2 to be constitutively activated. One outcome is increased tyrosine phosphorylation of PRMT5. This phosphorylation inhibits the binding of PRMT5 to WDR77, which is an enhancer of PRMT5 methyltransferase activity.