RIPK3 (Homo sapiens)
- Synonyms: RIPK3
- Species: Metazoa;Bilateria;Deuterostoma;Chordata;Vertebrata;Mammalia;Primates;Hominidae; Homo sapiens
- Short gene description: Receptor-interacting serine/threonine-protein kinase 3 (EC 220.127.116.11)(RIP-like protein kinase 3)(Receptor-interacting protein 3)(RIP-3) [Source:UniProtKB/Swiss-Prot;Acc:Q9Y572]
- Family: other
- Process: necroptosis,
- Pathways: TNF/NF-kappaB signaling,
- Criteria: manually curated
- Curator comment:
- WIKI: RIPK3-H_sapiens
- 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.)
Protein sequence [+]
RIPK3 | Homo sapiens | 9606 | length:518
- Smartdomain prediction information: SM00219
- Smartdomain prediction information: SM00220
- Prosite motif and domain information: PS00107
- Prosite motif and domain information: PS00108
- Profile motif and domain profile information: PS50011
- Interpro domain information: Q9Y572
- PFAM domain and domain family information: Q9Y572
View protein alignment and tree with Jalview:
Explore tree at phylomeDB:   Click here.
Homologs list [+]
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Gene Ontology [+]
|GO id||Name||Ontology type||Evidence|
|GO:0006468||protein amino acid phosphorylation||biological_proccess||IEA|
|GO:0007249||I-kappaB kinase/NF-kappaB cascade||biological_proccess||IEA|
|GO:0008624||induction of apoptosis by extracellular signals||biological_proccess||TAS|
|GO:0006464||protein modification process||biological_proccess||TAS|
|GO:0006917||induction of apoptosis||biological_proccess||IEA|
|GO:0004672||protein kinase activity||mollecular_function||IEA|
|GO:0004713||protein tyrosine kinase activity||mollecular_function||IEA|
|GO:0004674||protein serine/threonine kinase activity||mollecular_function||IEA|
|GO:0004704||NF-kappaB-inducing kinase activity||mollecular_function||IEA|
|GO:0003713||transcription coactivator activity||mollecular_function||TAS|
|GO:0004674||protein serine/threonine kinase activity||mollecular_function||TAS|
Check GO Evidence Codes here
Curated Isoforms [+]
Information from other databases [+]
- OMIM gene information: 605817
- OMIM disease information:
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