MLKL
GeneName
MLKL
Summary
MLKL, also known as mixed lineage kinase domain like protein, is a 54 kDa protein that plays a crucial role in the execution of necroptosis, a form of programmed cell death. It is expressed in various tissues and is localised to multiple cellular compartments, including the plasma membrane, cytoplasm, nucleus, and cell junctions. MLKL functions by binding to ATP and interacting with other proteins, facilitating the necroptotic process and cell surface receptor signalling pathways. Its ability to form homotrimers is essential for its function in mediating necroptosis in response to viral infections and other stress signals.
Importance
MLKL is relevant to: - Understanding the mechanisms of necroptosis, which has implications in various diseases, including neurodegenerative disorders and cancer. - Investigating viral pathogenesis, as it is involved in the defence response to viruses. - Exploring potential therapeutic targets for modulating cell death pathways in disease contexts. - Studying cell signalling pathways that influence inflammation and immune responses.
Top Products
For researchers studying MLKL, we highly recommend the top-selling recombinant antibody, Anti-MLKL antibody [EPR17514] (ab184718). This antibody has been validated in knockout models, ensuring reliable performance in various applications, including Western blotting (WB), immunohistochemistry (IHC), and immunocytochemistry (ICC). With 114 citations, it is well-regarded in the research community, making it an excellent choice for those seeking dependable MLKL detection in their studies. The Human MLKL ELISA Kit (ab263892) is an excellent option for researchers looking to measure MLKL levels in their samples.
Abcam Product Citation Summary
The data indicates a strong focus on the role of MLKL in necroptosis across various studies involving both human and mouse models. The use of multiple applications, including Western blotting and immunohistochemistry, highlights the importance of MLKL in understanding non-apoptotic cell death mechanisms, particularly in the context of head and neck squamous cell carcinoma (HNSCC) and other human cell types.
Abcam Product Citation Table
Domain
The protein kinase domain is catalytically inactive but contains an unusual pseudoactive site with an interaction between Lys-230 and Gln-356 residues (By similarity). Upon phosphorylation by RIPK3, undergoes an active conformation (By similarity).
The coiled coil region 2 is responsible for homotrimerization.
Function
Pseudokinase that plays a key role in TNF-induced necroptosis, a programmed cell death process (PubMed:22265413, PubMed:22265414, PubMed:22421439, PubMed:24316671). Does not have protein kinase activity (PubMed:22265413, PubMed:22265414, PubMed:22421439, PubMed:24316671). Activated following phosphorylation by RIPK3, leading to homotrimerization, localization to the plasma membrane and execution of programmed necrosis characterized by calcium influx and plasma membrane damage (PubMed:22265413, PubMed:22265414, PubMed:22421439, PubMed:24316671). In addition to TNF-induced necroptosis, necroptosis can also take place in the nucleus in response to orthomyxoviruses infection: following activation by ZBP1, MLKL is phosphorylated by RIPK3 in the nucleus, triggering disruption of the nuclear envelope and leakage of cellular DNA into the cytosol.following ZBP1 activation, which senses double-stranded Z-RNA structures, nuclear RIPK3 catalyzes phosphorylation and activation of MLKL, promoting disruption of the nuclear envelope and leakage of cellular DNA into the cytosol (By similarity). Binds to highly phosphorylated inositol phosphates such as inositolhexakisphosphate (InsP6) which is essential for its necroptotic function (PubMed:29883610).
Post-translational modifications
Phosphorylation by RIPK3 induces a conformational switch that is required for necroptosis (PubMed:22265413). It also induces homotrimerization and localization to the plasma membrane (PubMed:22265413).
Sequence Similarities
Belongs to the protein kinase superfamily.
Cellular localization
- Cytoplasm
- Cell membrane
- Nucleus
- Localizes to the cytoplasm and translocates to the plasma membrane on necroptosis induction (PubMed:24316671). Localizes to the nucleus in response to orthomyxoviruses infection (By similarity).
Alternative names
Mixed lineage kinase domain-like protein, hMLKL, MLKL