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Description

Receptor-interacting serine/threonine-protein kinase 3 (UniProt: EC:2.7.11.1, RIP-like protein kinase 3, Receptor-interacting protein 3, RIP-3, mRIP3) is encoded by the Ripk3 (also known as Rip3) gene (Gene ID: 56532) in murine species. RIPK3 is a serine/threonine protein kinase that is expressed in embryo and adult spleen, liver, testis, brain, and lung. Its protein kinase domain is localized in amino acids 22 to 293 in the N-terminal half and it also has a C-terminal RIP homolytic interaction motif (RHIM, aa 440-461), which mediates interaction with the RHIM motif of RIPK1 and facilitate the formation of a necrosome. RIPK3 is shown to activate both necroptosis and apoptosis. Activated RIPK3 forms a necrosis-inducing complex and mediates phosphorylation of MLKL, promoting MLKL localization to the plasma membrane and execution of programmed necrosis that is characterized by calcium influx and plasma membrane damage. Its location is mainly cytoplasmic, however, following infection, it can also be detected in the nucleus. RIPK3 also regulates apoptosis that is dependent on RIPK1, FADD, and CASP8, and is independent of MLKL and RIPK3 kinase activity. It phosphorylates RIPK1 and then RIPK1 and RIPK3 undergo reciprocal auto- and trans-phosphorylation. In some cell types, RIPK3 is also reported to restrict viral replication by promoting cell death-independent responses. Clone 8G7 is raised against an extended kinase domain (residues 2-353) of mouse RIPK3 and can detect forms that may not be detected by antibodies directed towards the C-terminus of the full-length RIPK3. (Ref.: Samson, AL., et al. (2021). Cell Death Differ. https://doi.org/10.1038/s41418-021-00742-x, Petrie, EJ., et al. (2019). Cell Rep. 28(13), 3309-3319).