Apoptosis Database

Description [+]

Synonyms: RIPK3, RIPK3, RECEPTOR-INTERACTING SERINE-THREONINE KINASE 3
Species: Metazoa;Bilateria;Deuterostoma;Chordata;Vertebrata;Mammalia;Rodentia; Mus musculus
Short gene description: Receptor-interacting serine/threonine-protein kinase 3 (EC 2.7.11.1)(RIP-like protein kinase 3)(Receptor-interacting protein 3)(RIP-3)(mRIP3) [Source:UniProtKB/Swiss-Prot;Acc:Q9QZL0]
Family: other
Process: necroptosis,
Pathways: TNF/NF-kappaB signaling,
Criteria: manually curated
Curator comment:
WIKI: RIPK3-M_musculus

References [+]

Receptor interacting protein kinase-3 determines cellular necrotic response to TNF-alpha.
He S, Wang L, Miao L, Wang T, Du F, Zhao L, Wang X
Smac mimetics induce apoptosis synergistically with TNF-alpha by triggering the formation of a caspase-8-activating complex containing receptor interacting protein kinase-1 (RIPK1). Caspase inhibitors block this form of apoptosis in many types of cells. However, in several other cell lines, caspase inhibitors switch the apoptotic response to necrosis. A genome wide siRNA screen revealed another member of the RIP kinase family, RIP3, to be required for necrosis. The expression of RIP3 in different cell lines correlates with their responsiveness to necrosis induction. The kinase activity of RIP3 is essential for necrosis execution. Upon induction of necrosis, RIP3 is recruited to RIPK1 to form a necrosis-inducing complex. Embryonic fibroblasts from RIP3 knockout mice are resistant to necrosis and RIP3 knockout animals are devoid of inflammation inflicted tissue damage in an acute pancreatitis model. These data indicate RIP3 as the determinant for cellular necrosis in response to TNF-alpha family of death-inducing cytokines. Cell. 2009 Jun 12;137(6):1100-11.

Phosphorylation-driven assembly of the RIP1-RIP3 complex regulates programmed necrosis and virus-induced inflammation.
Cho YS, Challa S, Moquin D, Genga R, Ray TD, Guildford M, Chan FK
Programmed necrosis is a form of caspase-independent cell death whose molecular regulation is poorly understood. The kinase RIP1 is crucial for programmed necrosis, but also mediates activation of the prosurvival transcription factor NF-kappaB. We postulated that additional molecules are required to specifically activate programmed necrosis. Using a RNA interference screen, we identified the kinase RIP3 as a crucial activator for programmed necrosis induced by TNF and during virus infection. RIP3 regulates necrosis-specific RIP1 phosphorylation. The phosphorylation of RIP1 and RIP3 stabilizes their association within the pronecrotic complex, activates the pronecrotic kinase activity, and triggers downstream reactive oxygen species production. The pronecrotic RIP1-RIP3 complex is induced during vaccinia virus infection. Consequently, RIP3(-/-) mice exhibited severely impaired virus-induced tissue necrosis, inflammation, and control of viral replication. Our findings suggest that RIP3 controls programmed necrosis by initiating the pronecrotic kinase cascade, and that this is necessary for the inflammatory response against virus infections. Cell. 2009 Jun 12;137(6):1112-23.

Structure & Sequence [+]

Pfam domains: (Pfam is a large collection of protein families.)

Source	Domain Name	Start	End
PFAM A	Pkinase	22	295
PFAM A	Pkinase_Tyr	22	291

Protein sequence [+]

Structure links:

Evolution [+]

Gene Ontology [+]

GO id	Name	Ontology type	Evidence
GO:0006468	protein amino acid phosphorylation	biological_proccess	IEA
GO:0006915	apoptosis	biological_proccess	IEA
GO:0006917	induction of apoptosis	biological_proccess	IDA
GO:0007249	I-kappaB kinase/NF-kappaB cascade	biological_proccess	IDA
GO:0000166	nucleotide binding	mollecular_function	IEA
GO:0004674	protein serine/threonine kinase activity	mollecular_function	IEA
GO:0004704	NF-kappaB-inducing kinase activity	mollecular_function	IDA
GO:0005524	ATP binding	mollecular_function	IEA
GO:0016740	transferase activity	mollecular_function	IEA
GO:0016301	kinase activity	mollecular_function	IEA
GO:0004872	receptor activity	mollecular_function	IEA
GO:0004672	protein kinase activity	mollecular_function	IDA
GO:0004713	protein tyrosine kinase activity	mollecular_function	IEA
GO:0005622	intracellular	cell_component	IDA
GO:0005737	cytoplasm	cell_component	IEA

Check GO Evidence Codes here

Information from other databases [+]

Gene related links:

Protein related links:

Other links

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RIPK3 (Mus musculus)