Mlkl
entrez
74568
canonical
uniprot
Q9D2Y4
canonical
ensembl
ENSMUSG00000012519
resolver
ensp
ENSMUSP00000055521
resolver
ensp
ENSMUSP00000113718
resolver
ensp
ENSMUSP00000165108
resolver
ensp
ENSMUSP00000165109
resolver
ensp
ENSMUSP00000165113
resolver
ensp
ENSMUSP00000165114
resolver
genesymbol
Mlkl
resolver
uniprot
Q8CIJ5
resolver
uniprot_entry
MLKL_MOUSE
resolver
uniprot_sec
Q8CIJ5
resolver
activity_regulation
ACTIVITY REGULATION: Activated via binding to highly phosphorylated inositol phosphates such as inositolhexakisphosphate (InsP6) which mediates the release of an N-terminal auto-inhibitory region (By similarity). Activation requires not only RIPK3-dependent phosphorylation but also binding to highly phosphorylated inositol phosphates (By similarity). {ECO:0000250|UniProtKB:Q8NB16}.
uniprot
proteins
amino_acid_sequence
MDKLGQIIKLGQLIYEQCEKMKYCRKQCQRLGNRVHGLLQPLQRLQAQGKKNLPDDITAALGRFDEVLKEANQQIEKFSKKSHIWKFVSVGNDKILFHEVNEKLRDVWEELLLLLQVYHWNTVSDVSQPASWQQEDRQDAEEDGNENMKVILMQLQISVEEINKTLKQCSLKPTQEIPQDLQIKEIPKEHLGPPWTKLKTSKMSTIYRGEYHRSPVTIKVFNNPQAESVGIVRFTFNDEIKTMKKFDSPNILRIFGICIDQTVKPPEFSIVMEYCELGTLRELLDREKDLTMSVRSLLVLRAARGLYRLHHSETLHRNISSSSFLVAGGYQVKLAGFELSKTQNSISRTAKSTKAERSSSTIYVSPERLKNPFCLYDIKAEIYSFGIVLWEIATGKIPFEGCDSKKIRELVAEDKKQEPVGQDCPELLREIINECRAHEPSQRPSVDGRSLSGRERILERLSAVEESTDKKV
uniprot
proteins
function
FUNCTION: Pseudokinase that plays a key role in TNF-induced necroptosis, a programmed cell death process (PubMed:23835476, PubMed:24012422, PubMed:24019532, PubMed:27321907, PubMed:32200799, PubMed:32296175). Does not have protein kinase activity (PubMed:24012422). 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 (PubMed:23835476, PubMed:24012422, PubMed:24019532, PubMed:27321907). In addition to TNF-induced necroptosis, necroptosis can also take place in the nucleus in response to orthomyxoviruses infection: following ZBP1 activation, which senses double-stranded Z-RNA structures, nuclear RIPK3 catalyzes phosphorylation and activation of MLKL, promoting disruption of the nuclear envelope and leakage of cellular DNA into the cytosol (PubMed:32200799, PubMed:32296175). Binds to highly phosphorylated inositol phosphates such as inositolhexakisphosphate (InsP6) which is essential for its necroptotic function (By similarity). {ECO:0000250|UniProtKB:Q8NB16, ECO:0000269|PubMed:23835476, ECO:0000269|PubMed:24012422, ECO:0000269|PubMed:24019532, ECO:0000269|PubMed:27321907, ECO:0000269|PubMed:32200799, ECO:0000269|PubMed:32296175}.
uniprot
proteins
mass_dalton
54317
uniprot
proteins
mutagenesis
MUTAGEN 219; /note="K->M: Abolishes ATP-binding and induces necroptosis in absence of exogeous stimuli and independently of RIPK3."; /evidence="ECO:0000269|PubMed:24012422"; MUTAGEN 239; /note="E->M: Retains ATP-binding ability."; /evidence="ECO:0000269|PubMed:24012422"; MUTAGEN 280; /note="L->P: Impaired ability to induce necroptosis."; /evidence="ECO:0000269|PubMed:24012422"; MUTAGEN 343; /note="Q->A: Retains ATP-binding ability and induces necroptosis in absence of exogeous stimuli and independently of RIPK3."; /evidence="ECO:0000269|PubMed:24012422"; MUTAGEN 345; /note="S->D: Mimics phosphorylation state and induces necroptosis in absence of exogeous stimuli and independently of RIPK3.e."; /evidence="ECO:0000269|PubMed:24012422"; MUTAGEN 385; /note="F->I: No effect."; /evidence="ECO:0000269|PubMed:24012422"; MUTAGEN 404..405; /note="SK->AA: Impairs interaction with RIPK3."; /evidence="ECO:0000269|PubMed:24095729"; MUTAGEN 404; /note="S->A: Impairs interaction with RIPK3."; /evidence="ECO:0000269|PubMed:24095729
uniprot
proteins
post_translational_modification
PTM: Phosphorylation by RIPK3 induces a conformational switch that is required for necroptosis (PubMed:24012422, PubMed:24095729, PubMed:32200799). It also induces homotrimerization and localization to the plasma membrane (By similarity). {ECO:0000250|UniProtKB:Q8NB16, ECO:0000269|PubMed:24012422, ECO:0000269|PubMed:24095729, ECO:0000269|PubMed:32200799}.
uniprot
proteins
protein_family
Protein kinase superfamily
uniprot
proteins
pubmed
15489334
uniprot
proteins
pubmed
16141072
uniprot
proteins
pubmed
21183079
uniprot
proteins
pubmed
22265413
uniprot
proteins
pubmed
23612963
uniprot
proteins
pubmed
23835476
uniprot
proteins
pubmed
24012422
uniprot
proteins
pubmed
24019532
uniprot
proteins
pubmed
24095729
uniprot
proteins
pubmed
27321907
uniprot
proteins
pubmed
27819681
uniprot
proteins
pubmed
32200799
uniprot
proteins
pubmed
32296175
uniprot
proteins
sequence_length
472
uniprot
proteins
subcellular_location
SUBCELLULAR LOCATION: Cytoplasm {ECO:0000269|PubMed:32200799, ECO:0000269|PubMed:32296175}. Cell membrane {ECO:0000269|PubMed:32200799}. Nucleus {ECO:0000269|PubMed:32200799, ECO:0000269|PubMed:32296175}. Note=Localizes to the cytoplasm and translocates to the plasma membrane on necroptosis induction (By similarity). Localizes to the nucleus in response to orthomyxoviruses infection (PubMed:32200799). {ECO:0000250|UniProtKB:Q8NB16, ECO:0000269|PubMed:32200799}.
uniprot
proteins