MLKL (mixed lineage kinase domain like pseudokinase)

Gene

• Entrez ID: 197259
• Gene name: Mixed lineage kinase domain like pseudokinase
• Gene symbol: MLKL
• Synonyms (NCBI Gene): hMLKL
• Chromosome: 16
• Chromosome location: 16q23.1
• Summary: 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 necrosi

miRNA

miRTarBase ID	miRNA	Experiments	Reference
MIRT1151088	hsa-miR-1587	CLIP-seq
MIRT1151089	hsa-miR-3147	CLIP-seq
MIRT1151090	hsa-miR-3201	CLIP-seq
MIRT1151091	hsa-miR-4422	CLIP-seq
MIRT1151092	hsa-miR-4496	CLIP-seq
MIRT1151093	hsa-miR-4674	CLIP-seq
MIRT1151094	hsa-miR-4712-3p	CLIP-seq
MIRT1151095	hsa-miR-4716-5p	CLIP-seq
MIRT1151096	hsa-miR-4781-3p	CLIP-seq
MIRT1151097	hsa-miR-4791	CLIP-seq
MIRT1151098	hsa-miR-617	CLIP-seq
MIRT2272585	hsa-miR-578	CLIP-seq

Gene ontology (GO)

GO ID	Ontology	Definition	Evidence	Reference
GO:0000166	Function	Nucleotide binding	IEA
GO:0004672	Function	Protein kinase activity	ISS
GO:0004674	Function	Protein serine/threonine kinase activity	IBA
GO:0005515	Function	Protein binding	IPI	22265413, 22265414, 29883609, 32296183
GO:0005524	Function	ATP binding	IDA	24219132
GO:0005524	Function	ATP binding	IEA
GO:0005634	Component	Nucleus	IEA
GO:0005634	Component	Nucleus	ISS
GO:0005737	Component	Cytoplasm	IBA
GO:0005737	Component	Cytoplasm	IDA	24316671
GO:0005737	Component	Cytoplasm	IEA
GO:0005829	Component	Cytosol	IDA
GO:0005829	Component	Cytosol	TAS
GO:0005886	Component	Plasma membrane	IDA	24316671, 29883610
GO:0005886	Component	Plasma membrane	IEA
GO:0007166	Process	Cell surface receptor signaling pathway	IEA
GO:0012501	Process	Programmed cell death	IEA
GO:0016020	Component	Membrane	IEA
GO:0019901	Function	Protein kinase binding	IEA
GO:0030054	Component	Cell junction	IDA
GO:0042802	Function	Identical protein binding	IPI	24316671
GO:0044877	Function	Protein-containing complex binding	IDA	22265414
GO:0051607	Process	Defense response to virus	IEA
GO:0051607	Process	Defense response to virus	ISS
GO:0070207	Process	Protein homotrimerization	IDA	24316671
GO:0070266	Process	Necroptotic process	IEA
GO:0070266	Process	Necroptotic process	IMP	22265414, 24316671, 29883610
GO:0097527	Process	Necroptotic signaling pathway	IBA
GO:0097527	Process	Necroptotic signaling pathway	IEA
GO:0097527	Process	Necroptotic signaling pathway	IMP	22265413
GO:0097528	Process	Execution phase of necroptosis	IDA	24316671
GO:0097528	Process	Execution phase of necroptosis	IEA
GO:0097528	Process	Execution phase of necroptosis	ISS

Other IDs

• MIM: 615153
• HGNC: 26617
• e!Ensembl: ENSG00000168404

Protein

• UniProt ID: Q8NB16
• Protein name: Mixed lineage kinase domain-like protein (hMLKL)
• Protein 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:
• PDB: 2MSV, 4M67, 4MWI, 5KNJ, 5KO1, 6BWK, 6D74, 6LK5, 6LK6, 6O5Z, 6UX8, 6ZLE, 6ZPR, 6ZVO, 6ZZ1, 7JW7, 7JXU, 7MON, 7NM2, 7NM4, 7NM5, 8SLZ
• Family and domains:

  Pfam

  Accession	ID	Position in sequence	Description	Type
  PF07714	PK_Tyr_Ser-Thr	209 → 466	Protein tyrosine and serine/threonine kinase	Domain

• Sequence:

  MENLKHIITLGQVIHKRCEEMKYCKKQCRRLGHRVLGLIKPLEMLQDQGKRSVPSEKLTT
  AMNRFKAALEEANGEIEKFSNRSNICRFLTASQDKILFKDVNRKLSDVWKELSLLLQVEQ
  RMPVSPISQGASWAQEDQQDADEDRRAFQMLRRDNEKIEASLRRLEINMKEIKETLRQYL
  PPKCMQEIPQEQIKEIKKEQLSGSPWILLRENEVSTLYKGEYHRAPVAIKVFKKLQAGSI
  AIVRQTFNKEIKTMKKFESPNILRIFGICIDETVTPPQFSIVMEYCELGTLRELLDREKD
  LTLGKRMVLVLGAARGLYRLHHSEAPELHGKIRSSNFLVTQGYQVKLAGFELRKTQTSMS
  LGTTREKTDRVKSTAYLSPQELEDVFYQYDVKSEIYSFGIVLWEIATGDIPFQGCNSEKI
  RKLVAVKRQQEPLGEDCPSELREIIDECRAHDPSVRPSVDEILKKLSTFSK

• Sequence length: 471

Pathways

KEGG:

Necroptosis
Cytosolic DNA-sensing pathway
TNF signaling pathway
Salmonella infection

Reactome:

TRP channels
RIPK1-mediated regulated necrosis

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