Tbio MLKL Mixed lineage kinase domain-like protein

Protein Summary

Description

Pseudokinase that plays a key role in TNF-induced necroptosis, a programmed cell death process. 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. Does not have protein kinase activity (PubMed:22265413, PubMed:22265414, PubMed:22421439, PubMed:24316671). Binds to highly phosphorylated inositol phosphates such as inositolhexakisphosphate (InsP6) which is essential for its necroptotic function (PubMed:29883610). 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. 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]

Uniprot Accession IDs

• Q8NB16
• A6NCE4
• Q8N6V0
• hMLKL

Gene Name

• MLKL

Ensembl ID

• ENST00000306247
• ENSP00000303118
• ENSG00000168404
• ENST00000308807
• ENSP00000308351

Symbol

• hMLKL

Knowledge Table

Most Knowledge About	Knowledge Value (0 to 1 scale)
virus perturbation	1
molecular function	0.96
histone modification site profile	0.77
interacting protein	0.76
transcription factor perturbation	0.74

Protein Classes

DTO Classes

Protein / Kinase / Protein Kinase / Tkl Group / Tkl-unique Family / Mixed Lineage Kinase Domain-like Protein

IDG Development Level Summary

Tdark

These are targets about which virtually nothing is known. They do not have known drug or small molecule activities
- AND - satisfy two or more of the following criteria:

Pubmed score: 540.49   (req: < 5)

Gene RIFs: 89   (req: <= 3)

Antibodies: 275   (req: <= 50)

Tbio

These targets do not have known drug or small molecule activities
- AND - satisfy two or more of the following criteria:

Pubmed score: 540.49   (req: >= 5)

Gene RIFs: 89   (req: > 3)

Antibodies: 275   (req: > 50)

- OR - satisfy the following criterion:

Gene Ontology Terms: 11

Tchem

Target has at least one ChEMBL compound with an activity cutoff of < 30 nM - AND - satisfies the preceding conditions

Active Ligand: 1

Tclin

Target has at least one approved drug - AND - satisfies the preceding conditions

Active Drug: 0