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Tchem
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 necropt ...more
Uniprot Accession IDs
Gene Name
Ensembl ID
  • ENST00000306247
  • ENSP00000303118
  • ENSG00000168404
  • ENST00000308807
  • ENSP00000308351

Symbol
  • hMLKL
Illumination Graph
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


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: 43   (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: 43   (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
Expression Data (0 Tissues)
No expression data found
Protein Sequence and Structure
Residue Counts
Protein Sequence
ProtVista Viewer
Related Tools (5)
ProKinO
Thumbnail image for ProKinO
The ProKinO is a protein kinase-specific ontology, which provides a controlled vocabulary of terms, their hierarchy, and relationships unifying sequence, structure, function, mutation and pathway information on kinases.
Target Illumination GWAS Analytics (TIGA)
Thumbnail image for Target Illumination GWAS Analytics (TIGA)
TIGA scores and ranks GWAS discovered associations according to the quantity and quality of the evidence supporting the association.
GENEVA
Thumbnail image for GENEVA
GENEVA (GENe Expression Variance Analysis) allows you to identify RNA-sequencing datasets from the Gene Expression Omnibus (GEO) that contain conditions modulating a gene or a gene signature.
GlyGen
Thumbnail image for GlyGen
GlyGen is a data integration and dissemination project for carbohydrate and glycoconjugate related data.
ARCHS4
Thumbnail image for ARCHS4
ARCHS4 provides access to gene-function predictions based on RNA-seq co-expression, and gene expression levels across cell and tissues.
Approved Drugs (0)
No approved drugs found
Protein-Protein Interactions (71)
RIPK3
Tchem
Family:  Kinase
Novelty:  0.00326006
Score:  0.989
Data Source:  Reactome,STRINGDB
PGAM5
Tbio
Family:  Enzyme
Novelty:  0.02046532
Score:  0.963
Data Source:  STRINGDB
RIPK1
Tchem
Family:  Kinase
Novelty:  0.00230565
Score:  0.957
Data Source:  Reactome,STRINGDB
HSP90AA1
Tchem
Novelty:  0.00016774
Score:  0.921
Data Source:  STRINGDB
NLRP3
Tchem
Novelty:  0.00043957
Score:  0.905
Data Source:  STRINGDB
TRPM7
Tchem
Family:  IC
Novelty:  0.00265096
Score:  0.885
Data Source:  STRINGDB
HSP90AB1
Tchem
Novelty:  0.00907961
Score:  0.878
Data Source:  STRINGDB
AMD1
Tchem
Family:  Enzyme
Novelty:  0.00231813
Score:  0.836
Data Source:  STRINGDB
CASP8
Tchem
Family:  Enzyme
Novelty:  0.00024321
Score:  0.813
Data Source:  STRINGDB
PCSK1
Tchem
Family:  Enzyme
Novelty:  0.00315256
Score:  0.804
Data Source:  STRINGDB
Pathways (589)
Programmed Cell Death (R-HSA-5357801)

Click on a row in the table to change the structure displayed.

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Items per page:
1 – 3 of 3
Data Source
Name
Explore in Pharos
Explore in Source
Reactome
Programmed Cell Death
Reactome
RIPK1-mediated regulated necrosis
Reactome
Regulated Necrosis
Name
Explore in Pharos
Explore in Source
Programmed Cell Death
RIPK1-mediated regulated necrosis
Regulated Necrosis
Viral Interactions (0)
No viral interactions found
Gene Ontology Terms (14)
Find Similar Targets
Items per page:
10
1 – 6 of 6
GO Term
Evidence
Assigned by
Inferred from Direct Assay (IDA)
UniProtKB
Inferred from Direct Assay (IDA)
UniProtKB
Inferred from Physical Interaction (IPI)
IntAct
Inferred from Biological aspect of Ancestor (IBA)
GO_Central
Inferred from Biological aspect of Ancestor (IBA)
GO_Central
Inferred from Electronic Annotation (IEA)
Ensembl
Disease Associations (null)
No disease associations found
GWAS Traits (5)
GWAS Trait
EFO ID
Study Count
SNP Count
Beta Count
Odds Ratio
Evidence (Mean Rank Score)
Provenance
1
1
0
1.3
75.2
2
1
0
1.2
72.1
1
1
0
1.1
70.5
telomere length
1
1
1
33.5
body height
1
1
1
21.2
GWAS Trait
EFO ID
Beta Count
Odds Ratio
Evidence (Mean Rank Score)
Provenance
0
1.3
75.2
0
1.2
72.1
0
1.1
70.5
telomere length
1
33.5
body height
1
21.2
Find similar targets by:
IDG Resources
No IDG generated resources found
Orthologs (9)
1 – 5 of 9
Species
Name
Source ID
Gene ID
OMA
EggNOG
Inparanoid
Chimp
mixed lineage kinase domain like pseudokinase
VGNC:13734
736069
Macaque
mixed lineage kinase domain like pseudokinase
710316
Mouse
MGI:1921818
74568
Rat
RGD:1592221
690743
Horse
mixed lineage kinase domain like pseudokinase
VGNC:20211
100068748
Species
Name
OMA
EggNOG
Inparanoid
Chimp
mixed lineage kinase domain like pseudokinase
Macaque
mixed lineage kinase domain like pseudokinase
Mouse
Rat
Horse
mixed lineage kinase domain like pseudokinase
Publication Statistics
PubMed Score 540.49
PubMed score by year
PubTator Score 101.88
PubTator score by year
Patents
Patents by year
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Related Publications
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0 of 0
PMID
Year
Title