FEATURES

FAMILY

DESCRIPTION

Also known as STING_BOVIN, STING1, TMEM173. Facilitator of innate immune signaling that acts as a sensor of cytosolic DNA from bacteria and viruses and promotes the production of type I interferon (IFN-alpha and IFN-beta). Innate immune response is triggered in response to non-CpG double-stranded DNA from viruses and bacteria delivered to the cytoplasm. 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 messenger produced by CGAS in response to DNA virus in the cytosol. Upon binding of c-di-GMP or cGAMP, STING oligomerizes, translocates from the endoplasmic reticulum and is phosphorylated by TBK1 on the pLxIS motif, leading to recruitment and subsequent activation of the transcription factor IRF3 to induce expression of type I interferon and exert a potent anti-viral state. In addition to promote the production of type I interferons, plays a direct role in autophagy. Following cGAMP-binding, STING1 buds from the endoplasmic reticulum into COPII vesicles, which then form the endoplasmic reticulum-Golgi intermediate compartment (ERGIC). The ERGIC serves as the membrane source for WIPI2 recruitment and LC3 lipidation, leading to formation of autophagosomes that target cytosolic DNA or DNA viruses for degradation by the lysosome. The autophagy- and interferon-inducing activities can be uncoupled and autophagy induction is independent of TBK1 phosphorylation (By similarity). Autophagy is also triggered upon infection by bacteria: following c-di-GMP-binding, which is produced by live Gram-positive bacteria, promotes reticulophagy (By similarity). Exhibits 2', 3' phosphodiester linkage-specific ligand recognition: can bind both 2'-3' linked cGAMP (2'-3'-cGAMP) and 3'-3' linked cGAMP but is preferentially activated by 2'-3' linked cGAMP. The preference for 2'-3'-cGAMP, compared to other linkage isomers is probably due to the ligand itself, whichs adopts an organized free-ligand conformation that resembles the STING1-bound conformation and pays low energy costs in changing into the active conformation. May be involved in translocon function, the translocon possibly being able to influence the induction of type I interferons (By similarity). May be involved in transduction of apoptotic signals via its association with the major histocompatibility complex class II (MHC-II) (By similarity). Homodimer; forms a homodimer in absence of cyclic nucleotide (c-di-GMP or cGAMP); 'Lys-63'-linked ubiquitination at Lys-150 is required for homodimerization (By similarity). Homotetramer; in presence of cyclic nucleotide (c-di-GMP or cGAMP), forms tetramers and higher-order oligomers through side-by-side packing (By similarity). Interacts (when phosphorylated) with IRF3; following activation and phosphorylation on the pLxIS motif by TBK1, recruits IRF3 (By similarity). Interacts with DDX58/RIG-I, MAVS and SSR2 (By similarity). Interacts with RNF5 and TRIM56 (By similarity). Interacts with TBK1; when homodimer, leading to subsequent production of IFN-beta (By similarity). Interacts with IFIT1 and IFIT2 (By similarity). Interacts with TRIM29; this interaction induces STING1 ubiquitination and subsequent degradation (By similarity). Associates with the MHC-II complex (By similarity). Interacts with STEEP; the interaction is increased upon cGAMP binding and promotes STING1 translocation to COPII vesicles (By similarity). Interacts with SEC24A, SEC24B and SEC24C; promoting translocation to COPII vesicles (By similarity). Interacts (when ubiquitinated) with SQSTM1; leading to relocalization to autophagosomes (By similarity). Interacts with SURF4 (By similarity). Interacts with HNRNPA2B1 (By similarity). Interacts with ZDHHC1; ZDHHC1 constitutively interacts with STING1 and in presence of DNA viruses activates it by promoting its cGAMP-induced oligomerization and the recruitment of downstream signaling components (By similarity). Interacts with ZDHHC11; in presence of DNA viruses promotes the recruitment of IRF3 to STING1 (By similarity). Interacts with TOMM70 (By similarity).

EXTERNAL LINKS

STING1

Stimulator of interferon genes protein

STING1

Molecular Synopsis