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. Rebsamen M. et al, DAI/ZBP1 recruits RIP1 and RIP3 through RIP homotypic interaction motifs to activate NF-kappaB. EMBO Rep. 10:916-922(2009).

2. Kaiser W.J. et al, Toll-like receptor 3-mediated necrosis via TRIF, RIP3, and MLKL. J. Biol. Chem. 288:31268-31279(2013).

Sequence Similarity

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

Tissue Specificity

Expressed in embryo and in adult spleen, liver, testis, heart, brain and lung.

Post-translational Modification

RIPK1 and RIPK3 undergo reciprocal auto- and trans-phosphorylation. Phosphorylation of Ser-204 plays a role in the necroptotic function of RIPK3. Phosphorylation at Ser-232 is required for binding MLKL. Phosphorylation at Thr-187 is important for its kinase activity, interaction with PELI1 and for its ability to mediate TNF-induced necroptosis (By similarity).; Polyubiquitinated with 'Lys-48' and 'Lys-63'-linked chains by BIRC2/c-IAP1 and BIRC3/c-IAP2, leading to activation of NF-kappa-B. Ubiquitinated by STUB1 leading to its subsequent proteasome-dependent degradation.

Subcellular Location

Mitochondrion, Cytosol, Plasma membrane.

UNIPROT

SwissProt: Q9QZL0 Mouse

SwissProt: Q9Z2P5 Rat

Synonyms