Anti-phospho-MLKL (Ser345) Antibody, clone 7C6.1 clone 7C6.1, from mouse

Mixed lineage kinase domain-like protein (UniProt: Q9D2Y4; also known as MLKL) is encoded by the Mlkl gene (Gene ID: 74568) in murine species. MLKL is a pseudokinase that plays a key role in TNF-induced necroptosis. MLKL is highly expressed in thymus, colon, intestine, liver, spleen and lung and is expressed at much lower level in skeletal muscle, heart and kidney. It is not detected in brain. MLKL is activated following phosphorylation by RIPK3 that induces a conformational switch, which is essential for necroptosis. The protein kinase domain of MLKL is catalytically inactive, but contains a pseudoactive site with an interaction between Lys-219 and Gln-343 residues. Upon phosphorylation by RIPK3, MLKL undergoes an active conformation and homotrimerization through its amino-terminal coiled-coil domain. Phosphorylation is also essential for homotrimerization of MLKL and its subsequent localization to the plasma membrane. Plasma membrane localization of MLKL is considered to be essential for Ca2+ influx, which is an early event of TNF-induced necroptosis. (Ref.: Cai, Z et al. (2014). Nat. Cell Biol. 16(1): 55-65).