Mixed lineage kinase domain like pseudokinase

Mixed lineage kinase domain like pseudokinase (MLKL) is a protein that in humans is encoded by the MLKL gene. ^[5]

MLKL
Available structures PDB Ortholog search: PDBe RCSB List of PDB id codes 2MSV, 4M67, 4MWI
Identifiers
Aliases	MLKL, hmixed lineage kinase domain-like, mixed lineage kinase domain like pseudokinase
External IDs	OMIM: 615153; MGI: 1921818; HomoloGene: 77416; GeneCards: MLKL; OMA:MLKL - orthologs
Gene location (Human) Chr. Chromosome 16 (human)[1] Band 16q23.1 Start 74,671,855 bp[1] End 74,700,960 bp[1]
Gene location (Mouse) Chr. Chromosome 8 (mouse)[2] Band 8|8 E1 Start 112,038,429 bp[2] End 112,064,809 bp[2]
RNA expression pattern Bgee Human Mouse (ortholog) Top expressed in granulocyte monocyte blood spleen upper lobe of left lung appendix myocardium of left ventricle right lung pancreatic epithelial cell mucosa of ileum Top expressed in bone marrow epithelium of stomach stroma of bone marrow endothelial cell of lymphatic vessel duodenum transitional epithelium of urinary bladder Paneth cell subcutaneous adipose tissue colon jejunum More reference expression data BioGPS n/a
Gene ontology Molecular function nucleotide binding protein binding ATP binding protein kinase binding protein kinase activity identical protein binding signal transducer activity protein-containing complex binding protein serine/threonine kinase activity JUN kinase kinase kinase activity Cellular component cytoplasm cytosol plasma membrane membrane Biological process necroptosis protein homotrimerization programmed cell death protein phosphorylation intracellular signal transduction cell surface receptor signaling pathway MAPK cascade Sources:Amigo / QuickGO
Orthologs Species Human Mouse Entrez 197259 74568 Ensembl ENSG00000168404 ENSMUSG00000012519 UniProt Q8NB16 Q9D2Y4 RefSeq (mRNA) NM_001142497 NM_152649 NM_029005 NM_001310613 RefSeq (protein) NP_001135969 NP_689862 NP_001297542 NP_083281 Location (UCSC) Chr 16: 74.67 – 74.7 Mb Chr 8: 112.04 – 112.06 Mb PubMed search [3] [4]
Wikidata
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Function

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.

Influence in diseases

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]. A unique neurodegenerative disease has been reported in association with a homozygous frameshift mutation, rs561839347, in MLKL that causes replacement of part of the C-terminal pseudokinase domain with a 21-residue sequence of random amino acids.^[6]

See also

• Necroptosis
• Cell death