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].
Function:
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.
Subunit:
Homotrimer; forms homotrimers on necroptosis induction. Interacts with RIPK3; the interaction is direct. Upon TNF-induced necrosis, forms in complex with PGAM5, RIPK1 and RIPK3. Within this complex, may play a role in the proper targeting of RIPK1/RIPK3 to its downstream effector PGAM5.
Subcellular Location:
Cytoplasm. Cell membrane. Note=Localizes to the cytoplasm and translocates to the plasma membrane on necroptosis induction.
Post-translational modifications:
Phosphorylation by RIPK3 induces a conformational switch that is required for necroptosis. It also induces homotrimerization and localization to the plasma membrane.
Similarity:
Belongs to the protein kinase superfamily.
Contains 1 protein kinase domain.
SWISS:
Q8NB16
Gene ID:
197259
Database links:
Entrez Gene: 197259 Human
Entrez Gene: 74568 Mouse
Entrez Gene: 690743 Rat
Omim: 615153 Human
SwissProt: Q8NB16 Human
SwissProt: Q9D2Y4 Mouse
Unigene: 119878 Human
Unigene: 207971 Mouse
Unigene: 105677 Rat
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