MLKL

Protein identityUniProt · HPA

UniProt accession

Q8NB16

Gene

MLKL

Ensembl

ENSG00000168404

Chromosome

16

Canonical length

471 aa

Protein class

Enzymes, Predicted intracellular proteins, Transporters

Subcellular location

Plasma membrane,Cell Junctions,Cytosol

Quaternary structure

Homotrimer

OverviewNCBI Gene

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]

Canonical amino-acid sequenceUniProt

471 residues, UniProt reviewed canonical sequence.

>Q8NB16|MLKL
     1  MENLKHIITL GQVIHKRCEE MKYCKKQCRR LGHRVLGLIK PLEMLQDQGK RSVPSEKLTT
    61  AMNRFKAALE EANGEIEKFS NRSNICRFLT ASQDKILFKD VNRKLSDVWK ELSLLLQVEQ
   121  RMPVSPISQG ASWAQEDQQD ADEDRRAFQM LRRDNEKIEA SLRRLEINMK EIKETLRQYL
   181  PPKCMQEIPQ EQIKEIKKEQ LSGSPWILLR ENEVSTLYKG EYHRAPVAIK VFKKLQAGSI
   241  AIVRQTFNKE IKTMKKFESP NILRIFGICI DETVTPPQFS IVMEYCELGT LRELLDREKD
   301  LTLGKRMVLV LGAARGLYRL HHSEAPELHG KIRSSNFLVT QGYQVKLAGF ELRKTQTSMS
   361  LGTTREKTDR VKSTAYLSPQ ELEDVFYQYD VKSEIYSFGI VLWEIATGDI PFQGCNSEKI
   421  RKLVAVKRQQ EPLGEDCPSE LREIIDECRA HDPSVRPSVD EILKKLSTFS K

LocalizationUniProt · AlphaFold · HPA

Whether an antibody against MLKL can act on the native protein depends on physical access: surface and secreted proteins are reachable by circulating antibodies, intracellular proteins usually are not.

Antibody reachability

Cell surface

Secreted

No

Transmembrane segments

0

Mean surface accessibility (rSASA)

0.28

Highest tissue expression

35 nTPM

Expression across tissuesHPA

Genetic constraint and essentialitygnomAD · DepMap

Does the body need this protein intact? Low LOEUF or a strong DepMap dependency means loss or blockade of the protein is likely to be felt.

gnomAD LOEUF (loss-of-function intolerance)

1.24

gnomAD pLI

0

gnomAD missense Z

-1.45

DepMap mean gene effect

0

DepMap dependency class

none

Cancer expressionTCGA

Across TCGA tumor cohorts, this protein is over-expressed in roughly 4% of surveyed tumor types (aggregate summary; per-cohort expression, alteration, and survival load in the interactive view).

OntologyGO

Biological processes

• cell surface receptor signaling pathway
• defense response to virus
• execution phase of necroptosis
• necroptotic process
• necroptotic signaling pathway
• protein homotrimerization

Molecular functions

• ATP binding
• identical protein binding
• protein kinase binding
• protein-containing complex binding

Cellular components

• cell junction
• cytoplasm
• cytosol
• nucleus
• plasma membrane

Protein domainsUniProt · Pfam · InterPro

• Protein kinase domain
• Serine-threonine/tyrosine-protein kinase, catalytic domain
• Protein kinase-like domain superfamily
• Adaptor protein Cbl, N-terminal domain superfamily
• Serine/Threonine Kinases and Pseudokinases
• Protein tyrosine and serine/threonine kinase
• Mixed lineage kinase domain-like, N-terminal domain
• MLKL-like, MCAfunc domain
• Mixed lineage kinase domain-like N-terminal domain

KeywordsUniProt

• ATP-binding
• Cell membrane
• Coiled coil
• Cytoplasm
• Membrane
• Necrosis
• Nucleotide-binding
• Nucleus
• Phosphoprotein

InteractionsUniProt · HPA

Protein binding partners of MLKL in the human serome: UniProt-annotated complex subunits plus reported interactors. Each links to its own Seroatlas record.

• RIPK3
• RIPK1