Molecular Target Synopsis
Overview
Domains and Structures
Drugs and Clinical Candidates
Druggability
Chemistry
Ligand Efficiency Plot
Pathways
Family Cladogram
Interaction Network
Gene Expression
Gene Copy Number Variation
RNAi
Mutations
Germline Genetics

MLKL (Q8NB16) - Overview - Molecular Target Synopsis

Protein


MLKL, Mixed lineage kinase domain-like protein
UniProt Q8NB16

Also Known as MLKL_HUMAN, MLKL

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). Homooligomer (PubMed:29883610). Homotrimer; forms homotrimers on necroptosis induction. Interacts with RIPK3; the interaction is direct. Upon TNF-induced necrosis, forms in complex with PGAM5, RIPK1 and RIPK3. Within this complex, may play a role in the proper targeting of RIPK1/RIPK3 to its downstream effector PGAM5.

6BWK
CRYSTAL STRUCTURE OF THE HUMAN MLKL PSEUDOKINASE DOMAIN T357E/S358E MUTANT
RCSB/PDB
Inspect Structure
See all 3D Structures for MLKL

Isoforms / Transcripts (Protein Coding)


Sub-cellular localization


UniProt: MLKL is active in the following subcellular-locations: cell membrane, cytoplasm.
GO terms: MLKL is active in the following subcellular-locations: cytoplasm, cytosol, plasma membrane.



UniProt
GO terms

Gene Copy Number Variation


In COSMIC - Cell Lines Project MLKL has gain in 3 cell-lines, loss in 3 cell-lines and no signal in 998 cell-lines. (see details)

Gene Expression


In NCI60, the highest expressing cell lines are: SR, LOXIMVI, RPMI_8226

In Array Express (RNA-seq of 675 commonly used human cancer cell lines), the highest expressing cell lines are: HCC2270, TYK-nu.CP-r, GTL-16

In Array Express (RNA-seq of long poly adenylated RNA and long non poly adenylated RNA from ENCODE cell lines), the highest expressing cell lines are: HSMM, NHLF, SK-N-SH

(see details)

RNA Interference


MLKL was reported in the following RNAI studies:

Cell - Large Scale Profiling of Kinase Dependencies in Cancer Cell Lines, the highest RNAi cell lines are: TE6, TE14. (see details)

3D Structures


For MLKL there are:
6 structures (7 chains) solved
3 are solved in complex with at least one small molecule ligand



(see details)
Molecular Target 3D Synopsis

Screening and Chemistry


MLKL has been screened with 7 compounds (7 bioactivities). (see details)