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RIPK3

The product of this gene is a member of the receptor-interacting protein (RIP) family of serine/threonine protein kinases, and contains a C-terminal domain unique from other RIP family members. The encoded protein is predominantly localized to the cytoplasm, and can undergo nucleocytoplasmic shuttling dependent on novel nuclear localization and export signals. It is a component of the tumor necrosis factor (TNF) receptor-I signaling complex, and can induce apoptosis and weakly activate the NF-kappaB transcription factor.
Protein class

Enzymes, Metabolic proteins

Predicted location

Intracellular

Single cell type specificity

Cell type enhanced (Distal enterocytes, Exocrine glandular cells, Proximal enterocytes, Gastric mucus-secreting cells, Paneth cells)

Immune cell specificity

Low immune cell specificity

Cell line specificity

Cell line enhanced (CAPAN-2, HDLM-2, OE19, SK-BR-3)

Interaction

Interacts (via RIP homotypic interaction motif) with RIPK1 (via RIP homotypic interaction motif); this interaction induces RIPK1 phosphorylation and formation of a RIPK1-RIPK3 necrosis-inducing complex (PubMed:10339433, PubMed:11734559, PubMed:19524512, PubMed:29681455). Interacts with MLKL; the interaction is direct and triggers necroptosis (PubMed:22265413, PubMed:22421439). Interacts with ZBP1 (via RIP homotypic interaction motif); interaction with ZBP1 activates RIPK3, triggering necroptosis (By similarity). Upon TNF-induced necrosis, the RIPK1-RIPK3 dimer further interacts with PGAM5 and MLKL; the formation of this complex leads to PGAM5 phosphorylation and increase in PGAM5 phosphatase activity (PubMed:22265413, PubMed:22265414, PubMed:22421439). Binds TRAF2 and is recruited to the TNFR-1 signaling complex (PubMed:29883609). Interacts with PYGL, GLUL and GLUD1; these interactions result in activation of these metabolic enzymes (PubMed:19498109). Interacts with BIRC2/c-IAP1, BIRC3/c-IAP2 and XIAP/BIRC4 (PubMed:21931591). Interacts with ARHGEF2 (PubMed:21887730). Interacts with PELI1 (via atypical FHA domain); the phosphorylated form at Thr-182 binds preferentially to PELI1 (PubMed:29883609). Interacts with BUB1B, TRAF2 and STUB1 (PubMed:29883609). Interacts with CASP6 (PubMed:32298652). Component of the AIM2 PANoptosome complex, a multiprotein complex that drives inflammatory cell death (PANoptosis) (By similarity). (Microbial infection) Interacts (via RIP homotypic interaction motif/RHIM) with herpes simplex virus 1/HHV-1 protein RIR1/ICP6 (via RHIM); this interaction may induce heteromeric amyloid assemblies and prevent necroptosis activation. (Microbial infection) Interacts (via RIP homotypic interaction motif/RHIM) with herpes simplex virus 2/HHV-2 protein RIR1/ICP10 (via RHIM); this interaction prevents necroptosis activation.

Molecular function

Kinase, Serine/threonine-protein kinase, Transferase

More Types Infomation

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