STING1 protein

The STING1 protein (STING1 stands for Stimulator Of Interferon Response CGAMP Interactor 1) is a protein that is encoded by the gene of the same name located on chromosome 5q31.2. Alternative splicing of the gene leads to several transcript variants.

The STING1 protein is an important regulator of the innate immune response to viral and bacterial infections. STING1 is a PPR, a pattern recognition receptor that recognizes cytosolic nucleic acids and transmits signals that activate type I interferon responses. The STING protein has also been shown to play a role in apoptotic signaling by binding to the major type II histocompatibility complex.

STING facilitates innate immune signaling, and acts as a sensor for cytosolic DNA of bacteria and viruses to stimulate type I interferon (IFN-alpha and IFN-beta) production (Ishikawa H et al. 2008). The innate immune response is triggered in response to non-CpG double-stranded DNA from viruses and bacteria that enters the cytoplasm (Burdette DL et al. 2011). STING acts by binding cyclic dinucleotides: recognizes and binds cyclic di-GMP (c-di-GMP), a second messenger produced by bacteria, and cyclic GMP-AMP (cGAMP), a second messenger produced by cGAS in response to DNA viruses in the cytosol (Domizio JD et al. 2022).

GOF (gain of function) mutations in the STING gene are the cause of STING-associated vasculopathy (SAVI), which occurs in childhood.

1. Burdette DL et al. (2011) STING is a direct innate immune sensor of cyclic di-GMP. Nature 478(7370):515-518.
2. David C et al. (2022) Lung Inflammation in STING-Associated Vasculopathy with Onset in Infancy (SAVI). Cells 11:318.
3. Domizio JD et al. (2022) The cGAS-STING pathway drives type I IFN immunopathology in COVID-19. Nature 603(7899):145-151.
4. Ferguson PJ (2008) Neutrophil dysfunction in a family with a SAPHO syndrome-like phenotype. Arthritis Rheum 58: 3264-3269
5. Frémond ML et al.(2021) Overview of STING-associated vasculopathy with onset in infancy (SAVI) among 21 patients. J Allergy Clin Immunol Pract. 9: 803-818.
6. Ishikawa H et al. (2008) STING is an endoplasmic reticulum adaptor that facilitates innate immune signaling. Nature 455(7213):674-678