Atypical MAPK protein. Phosphorylates microtubule-associated protein 2 (MAP2) and MAPKAPK5. The precise role of the complex formed with MAPKAPK5 is still unclear, but the complex follows a complex set of phosphorylation events: upon interaction with atypical MAPKAPK5, ERK3/MAPK6 is phosphorylated at Ser-189 and then mediates phosphorylation and activation of MAPKAPK5, which in turn phosphorylates ERK3/MAPK6. May promote entry in the cell cycle (By similarity). ATP + L-seryl-[protein] = ADP + H(+) + O-phospho-L-seryl-[protein] ATP + L-threonyl-[protein] = ADP + H(+) + O-phospho-L-threonyl-[protein] Activated by phosphorylation at Ser-189. Heterodimer with ERK4/MAPK4. Interacts with (via FRIEDE motif) MAPKAPK5 (By similarity). Interacts with UBE3A; this interaction may be indirect and mediated by HERC2, possibly via HERC2 interaction with NEURL4 (By similarity). Translocates to the cytoplasm following interaction with MAPKAPK5. Highest levels within the nervous system, expressed in different tissues, mostly in skeletal muscle. Expressed at highest levels early in development. In contrast to classical MAPKs, the TXY motif within the activation loop is replaced by the SEG motif, whose phosphorylation activates the MAP kinases. Phosphorylated at Ser-189 by PAK1, PAK2 and PAK3 resulting in catalytic activation. Phosphorylated by MAPKAPK5 at other sites (By similarity). Ubiquitination at Met-1 leads to degradation by the proteasome pathway. Belongs to the protein kinase superfamily. CMGC Ser/Thr protein kinase family. MAP kinase subfamily.