Molecular Target Synopsis
Overview
Domains and Structures
Drugs and Clinical Candidates
Druggability
Chemistry
Ligand Efficiency Plot
Pathways
Family Cladogram
Interaction Network
Gene Expression
Gene Copy Number Variation
RNAi
Mutations
Germline Genetics

RIPK3 (Q9Y572) - Overview - Molecular Target Synopsis

Protein


RIPK3, Receptor-interacting serine/threonine-protein kinase 3
Enzyme Classification 2.7.11.1
UniProt Q9Y572

Also Known as RIPK3_HUMAN, RIPK3, RIP3

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. 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. 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. Interacts with MLKL; the interaction is direct. Binds TRAF2 and is recruited to the TNFR-1 signaling complex. Interacts with PYGL, GLUL and GLUD1; these interactions result in activation of these metabolic enzymes. Interacts with BIRC2/c-IAP1, BIRC3/c-IAP2 and XIAP/BIRC4. Interacts with ARHGEF2. 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 ZBP1.

5ZCK
4 RESIDUE FRAGMENT OF
PEPTIDE FROM RECEPTOR-INTERACTING SERINE/THREONINE-PROTEINKINASE 3
IN THE STRUCTURE OF
STRUCTURE OF THE RIP3 CORE REGION
RCSB/PDB
Inspect Structure
See all 3D Structures for RIPK3

Isoforms / Transcripts (Protein Coding)


Sub-cellular localization


UniProt: RIPK3 is active in the following subcellular-locations: cell membrane, cytoplasm, cytosol, mitochondrion.
GO terms: RIPK3 is active in the following subcellular-locations: cytosol, mitochondrion, plasma membrane.



UniProt
GO terms

Gene Copy Number Variation


In COSMIC - Cell Lines Project RIPK3 has gain in 3 cell-lines, loss in 1 cell-lines and no signal in 1001 cell-lines. (see details)

Gene Expression


In NCI60, the highest expressing cell lines are: COLO205, EKVX, HS578T

In Array Express (RNA-seq of 675 commonly used human cancer cell lines), the highest expressing cell lines are: OCUM-1, THP-1, UKE-1

In Array Express (RNA-seq of long poly adenylated RNA and long non poly adenylated RNA from ENCODE cell lines), the highest expressing cell lines are: SK-N-SH, NHLF, HSMM

(see details)

RNA Interference


RIPK3 was reported in the following RNAI studies:

Cell - Large Scale Profiling of Kinase Dependencies in Cancer Cell Lines, the highest RNAi cell lines are: CROE33, SCC90. (see details)

3D Structures


For RIPK3 there are:
2 structures (5 chains) solved
0 are solved in complex with at least one small molecule ligand



(see details)
Molecular Target 3D Synopsis

Screening and Chemistry


RIPK3 has been screened with 33 compounds (34 bioactivities), 4 compounds have bioactivities that show binding affinity of <= 500nM (4 bioactivities). (see details)