RIP3 Rabbit Polyclonal Antibody

Function

Receptor-interacting serine/threonine-protein kinase 3 is an enzyme that in humans is encoded by the RIPK3 gene. 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. Essential for necroptosis, a programmed cell death process in response to death-inducing TNF-alpha family members. Upon induction of necrosis, RIPK3 interacts with, and phosphorylates RIPK1 and MLKL to form a necrosis-inducing complex. RIPK3 binds to and enhances the activity of three metabolic enzymes: GLUL, GLUD1, and PYGL. These metabolic enzymes may eventually stimulate the tricarboxylic acid cycle and oxidative phosphorylation, which could result in enhanced ROS production.

Background References

1. Liu Y. et. al. RIP1/RIP3-regulated necroptosis as a target for multifaceted disease therapy (Review). Int J Mol Med. 2019 Sep

2. Zhang T. et. al. CaMKII is a RIP3 substrate mediating ischemia- and oxidative stress-induced myocardial necroptosis. Nat Med. 2016 Feb

Sequence Similarity

Belongs to the protein kinase superfamily. TKL Ser/Thr protein kinase family.

Tissue Specificity

Highly expressed in the pancreas. Detected at lower levels in heart, placenta, lung and kidney. Isoform 3 is significantly increased in colon and lung cancers.

Post-translational Modification

RIPK1 and RIPK3 undergo reciprocal auto- and trans-phosphorylation. Phosphorylation of Ser-199 plays a role in the necroptotic function of RIPK3. Phosphorylation at Ser-227 is required for binding MLKL. Phosphorylation at Thr-182 is important for its kinase activity, interaction with PELI1 and PELI1-mediated 'Lys-48'-linked polyubiquitination and for its ability to mediate TNF-induced necroptosis.; Polyubiquitinated with 'Lys-48' and 'Lys-63'-linked chains by BIRC2/c-IAP1 and BIRC3/c-IAP2, leading to activation of NF-kappa-B. Polyubiquitinated with 'Lys-48'-linked chains by PELI1 leading to its subsequent proteasome-dependent degradation. Ubiquitinated by STUB1 leading to its subsequent proteasome-dependent degradation.

Subcellular Location

Cytoplasm, cytosol, Nucleus.

UNIPROT

SwissProt: Q9Y572 Human

SwissProt: Q9QZL0 Mouse

SwissProt: Q9Z2P5 Rat

Synonyms