Mixed lineage kinase domain like pseudokinase explained

Mixed lineage kinase domain like pseudokinase (MLKL) is a protein that in humans is encoded by the MLKL gene.[1]

Function

This gene belongs to the protein kinase superfamily. The encoded protein contains a protein kinase-like domain; however, is thought to be inactive because it lacks several residues required for activity. This protein plays a critical role in tumor necrosis factor (TNF)-induced necroptosis, a programmed cell death process, via interaction with receptor-interacting protein 3 (RIP3), which is a key signaling molecule in necroptosis pathway. Inhibitor studies and knockdown of this gene inhibited TNF-induced necrosis.

Influence in diseases

High levels of this protein and RIP3 are associated with inflammatory bowel disease in children. Alternatively spliced transcript variants have been described for this gene. [provided by RefSeq, Sep 2015]. A unique neurodegenerative disease has been reported in association with a homozygous frameshift mutation, rs561839347, in MLKL that causes replacement of part of the C-terminal pseudokinase domain with a 21-residue sequence of random amino acids.[2]

See also

Further reading

Notes and References

  1. Web site: Entrez Gene: Mixed lineage kinase domain like pseudokinase. 2017-12-31.
  2. Faergeman SL, Evans H, Attfield KE, Desel C, Kuttikkatte SB, Sommerlund M, Jensen LT, Frokiaer J, Friese MA, Matthews PM, Luchtenborg C, Brügger B, Oturai AB, Dendrou CA, Fugger L. 6. A novel neurodegenerative spectrum disorder in patients with MLKL deficiency. Cell Death & Disease. 11. 5. Art. No. 303. 2020. 10.1038/s41419-020-2494-0. free. 32358523. 7195448.