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Description

Mixed lineage kinase domain-like protein (UniProt: Q8NB16, also known as hMLKL) is encoded by the MLKL gene (Gene ID: 197259) in human. MLKL is a pseudokinase that plays a key role in TNF-induced necroptosis, a programmed cell death process. MLKL contains a protein kinase-like domain, but it lacks several residues required for activity. Its ATP-binding site is located within amino acids 209-217. Two isoforms of MLKL have been described that are produced by alternative splicing. It contains two coiled coil regions (aa 55-84 and 139-180) and coiled coil region 2 is shown to be responsible for its homotrimerization. MLKL is phosphorylated on Thr357/Ser358 by RIP3 kinase that leads to its oligomerization. The oligomeric MLKL then translocates from cytosol to plasma membrane and intracellular membranes where it bind to phosphatidylinositol and cardiolipin and disrupts membrane integrity leading to necrotic cell death. MLKL is reported to play a critical role in TNF-induced necroptosis. (Ref.: Wang, H., et al (2014). Mol. Cell 54(1), 133-146).