1.A.140.1.1
STING of 379 aas and either 4 or 6 probable TMSs in a 2 + 2 (+ 2) TMS arrangement.  The last two putative TMSs are not as hydrophobic as the first four. STING is a facilitator of innate immune signaling that acts as a sensor of cytosolic dsDNA from bacteria and viruses and promotes the production of type I interferons (IFN-alpha and IFN-beta) (Ishikawa and Barber 2008, Shang et al. 2019). Moreover, an alternatively spliced STING isoform localizes in the cytoplasmic membrane and directly senses extracellular cGAMP (Le Naour et al. 2020) (see also 2.A.48.1.1). Zhang et al. 2022 presented a vivid panorama of STING biology, taking into account the details of the biochemical assay and structural information, especially its versatile outputs and functions beyond IFN induction. They also summarized the roles of STING in the pathogenesis of various diseases and highlighted the development of small-molecular compounds targeting STING for disease treatment.  The cGAS-STING innate immune pathway has emerged as a driver of inflammation in a variety of settings such as virus infection, cellular stress, and tissue damage. The pathway detects microbial and host-derived double-stranded DNA (dsDNA) in the cytosol, and triggers the production of type I interferons through the activation of IRF3. The detailed mechanistic and biochemical understanding of the pathway has enabled the development of pharmacological agents for the treatment of chronic inflammation and cancer.  STING is an ER-localized transmembrane protein; upon emergence of cytosolic dsDNA, STING exits the ER and migrates sequentially to the Golgi, recycling endosomes, and lysosomes. The intracellular translocation of STING is essential for activation and inactivation of STING signalling. Recent insights into the regulators of the membrane traffic of STING and STING-associated autoinflammatory diseases has been reviewed (Taguchi 2023).  The activity of STING as a proton channel has been reported (Liu 2024).