receptor interacting serine/threonine kinase 1
The information on this page was automatically extracted from online scientific databases.
From NCBI Gene:
This gene encodes a member of the receptor-interacting protein (RIP) family of serine/threonine protein kinases. The encoded protein plays a role in inflammation and cell death in response to tissue damage, pathogen recognition, and as part of developmental regulation. RIPK1/RIPK3 kinase-mediated necrosis is referred to as necroptosis. Genetic disruption of this gene in mice results in death shortly after birth. [provided by RefSeq, Aug 2017]
Serine-threonine kinase which is a key regulator of TNF-mediated apoptosis, necroptosis and inflammatory pathways (PubMed:25459879, PubMed:31827281, PubMed:31827280). Exhibits kinase activity-dependent functions that trigger cell death and kinase-independent scaffold functions regulating inflammatory signaling and cell survival (PubMed:11101870, PubMed:25459879). Initiates ripoptocide which describes cell death that is dependent on RIPK1, be it apoptosis or necroptosis (PubMed:31457011). Upon binding of TNF to TNFR1, RIPK1 is recruited to the TNF-R1 signaling complex (TNF-RSC also known as complex I) where it acts as a scaffold protein promoting cell survival, in part, by activating the canonical NF-kB pathway (By similarity). Specific conditions can however activate RIPK1, and its kinase activity then regulates assembly of two death-inducing complexes, namely complex IIa (RIPK1-FADD-CASP8) and the complex IIb (RIPK1-RIPK3-MLKL) and these complexes respectively drive apoptosis or necroptosis, a regulated form of necrosis (PubMed:19524513, PubMed:19524512, PubMed:29440439, PubMed:30988283). Also involved in inflammatory response by promoting transcriptional production of pro-inflammatory cytokines, such as interleukin-6 (IL6) (PubMed:31827281, PubMed:31827280). During embryonic development suppresses apoptosis and necroptosis and prevents the interaction of TRADD with FADD thereby limiting aberrant activation of CASP8 (By similarity). Phosphorylates DAB2IP at 'Ser-728' in a TNF-alpha-dependent manner, and thereby activates the MAP3K5-JNK apoptotic cascade (PubMed:17389591). Required for ZBP1-induced NF-kappa-B activation and activation of NF-kappa-B by DNA damage and IR (By similarity).
Covered on Genetics Home Reference:
From NCBI Gene:
- Immunodeficiency 57
- AUTOINFLAMMATION WITH EPISODIC FEVER AND LYMPHADENOPATHY
Immunodeficiency 57 (IMD57): An autosomal recessive primary immunodeficiency characterized by lymphopenia and recurrent viral, bacterial, and fungal infections. Patients exhibit early-onset inflammatory bowel disease involving the upper and lower gastrointestinal tract, and develop progressive polyarthritis. [MIM:618108]
Defects in RIPK1 are the cause of cleavage-resistant RIPK1-induced autoinflammatory syndrome (CRIA), an autosomal dominant syndrome characterized by fevers and pronounced lymphadenopathy beginning in early childhood and continuing throughout adulthood (PubMed:31827281, PubMed:31827280). Patients experience fevers occurring approximately every 2-4 weeks, lasting 1-7 days, and reaching temperatures as high as 40-41 degrees Celsius (PubMed:31827281, PubMed:31827280). In contrast to more severe autoinflammatory disorders, no signs of rash, arthritis, genital ulcers or end-stage organ damage are observed, and the conditions are not threatening life of the patients (PubMed:31827281, PubMed:31827280). The disease is caused by mutations affecting the gene represented in this entry (PubMed:31827281, PubMed:31827280). Defects are caused by strong RIPK1-dependent activation of inflammatory signaling pathways and overproduction of inflammatory cytokines and chemokines, such as interleukin-6 (IL6) and TNF (PubMed:31827281, PubMed:31827280).