MLKL
MLKL (mixed lineage kinase domain like pseudokinase, also known as FLJ34389) is a pseudokinase that executes TNF-induced necroptosis, a programmed form of cell death. It lacks protein kinase activity and is activated by RIPK3-mediated phosphorylation. Browse Assay Genie's current range of MLKL research reagents below, or read on for the biology behind the target.
MLKL is a pseudokinase with a key role in TNF-induced necroptosis, a programmed cell death process. It does not have protein kinase activity. Instead, it is activated following phosphorylation by RIPK3, which leads to homotrimerisation, localisation to the plasma membrane and execution of programmed necrosis. This form of death is characterised by calcium influx and plasma membrane damage. MLKL also binds highly phosphorylated inositol phosphates such as inositol hexakisphosphate (InsP6), which is essential for its necroptotic function.
Necroptosis can also occur in the nucleus. In response to orthomyxovirus infection, ZBP1 senses double-stranded Z-RNA structures and activates the pathway. Nuclear RIPK3 then phosphorylates and activates MLKL, which disrupts the nuclear envelope and allows cellular DNA to leak into the cytosol.
The MLKL gene belongs to the protein kinase superfamily and is listed by HGNC in the pseudokinase gene group. The encoded protein contains a protein kinase-like domain but is thought to be inactive because it lacks several residues required for catalysis. UniProt records localisation to the cytoplasm, cell membrane and nucleus, and alternatively spliced transcript variants have been described. Inhibitor studies and knockdown of the gene inhibited TNF-induced necrosis, and high levels of MLKL and RIP3 are associated with inflammatory bowel disease in children. The mouse ortholog is Mlkl.
MLKL is a key effector of TNF-induced necroptosis, acting downstream of RIPK3 to drive plasma membrane damage and programmed necrosis.
Phosphorylation by RIPK3, homotrimerisation and membrane localisation make MLKL a focus for dissecting how programmed necrosis is executed.
ZBP1-dependent, RIPK3-mediated activation of MLKL in the nucleus links orthomyxovirus infection to nuclear envelope disruption and DNA leakage.
High levels of MLKL and RIP3 are associated with inflammatory bowel disease in children, making this pathway relevant to gut inflammation studies.
MLKL is a pseudokinase that plays a key role in TNF-induced necroptosis. After RIPK3 phosphorylates it, MLKL homotrimerises, moves to the plasma membrane and causes calcium influx and membrane damage. It has no protein kinase activity of its own.
The HGNC name is mixed lineage kinase domain like pseudokinase, previously mixed lineage kinase domain-like. The alias FLJ34389 is also recorded, and UniProt calls the protein mixed lineage kinase domain-like protein. Alternatively spliced transcript variants have been described for the gene.
MLKL has a mouse ortholog, Mlkl; check the datasheet of any product for its validated reactivity. NCBI Gene reports that high levels of MLKL and RIP3 are associated with inflammatory bowel disease in children.
Necroptosis pathway partners, cell death regulators and inflammation-related targets with products at Assay Genie.
Gene and protein annotations from HGNC, NCBI Gene and UniProt Q8NB16; product specifications from Assay Genie datasheets.