MLKL — Mixed lineage kinase domain like pseudokinase
MLKL belongs to a gene co-expression module in 3 of 28 SCUBA cell types. Each module groups genes that rise and fall together in that cell type; the genes it shares a module with are its closest co-expression partners there.
MLKL's module in each cell type
| Cell type | Module | Shares the module with | |
|---|---|---|---|
| Endothelial | Notch Ligand Signaling Endothelial cell development | DLL1, ITM2A, KRT222, LTBR, SLC2A3, TRA2B, ZC3HAV1, ZNF436 | View in SCUBA |
| Macrophages | Antiviral ISG Response Antiviral | ADAR, APOL6, ARID5A, CLEC7A, DDX60, DTX3L, EIF2AK2, ERICH1 +29 more | View in SCUBA |
| Pericytes | TGF-beta Negative Feedback Inflammatory | CTNND1, DAZAP2, EMP1, KAT6A, KBTBD2, KLF7, RCAN1, RGS3 +6 more | View in SCUBA |
About the gene
| Synonyms | FLJ34389 |
|---|---|
| Chromosome | 16: 74671855-74700960 |
| Predicted location | Intracellular |
| Essential gene | No |
| Protein class | Enzymes, Predicted intracellular proteins, Transporters |
| Biological process | Necrosis |
Function
Pseudokinase that plays a key role in TNF-induced necroptosis, a programmed cell death process. Does not have protein kinase activity. 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. 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.
Human Protein Atlas · Open Targets · UniProt
Gene annotation from the Human Protein Atlas and UniProt; see sources & licences.