– Mitogen-activated protein kinase kinase kinase kinase 5, also known as Kinase homologous to SPS1/STE2, MAPK/ERK kinase kinase kinase 5, MEK kinase kinase 5, and MAP4K5, is a cytoplasm protein that belongs to the protein kinase superfamily, STE Ser/Thr protein kinase family and STE2 subfamily. MAP4K5 is ubiquitously expressed in all tissues examined, with high levels in the ovary, testis, and prostate. It contains one CNH domain and one protein kinase domain. MAP4K5 is highly similar to yeast SPS1/STE2 kinase. Yeast SPS1/STE2 functions near the beginning of the MAP kinase signal cascades that are essential for yeast pheromone response. MAP4K5 has been shown to interact with CRKL and TRAF2. This kinase was shown to activate Jun kinase in mammalian cells. MAP4K5 is an early component of MAP kinase signal cascades. It may play a role in the response to environmental stress. MAP4K5 appears to act upstream of the JUN N-terminal pathway.