Protein: Stimulator of interferon genes protein (STING) (Transmembrane protein 173) (E7F4N7)
Organism: Danio rerio (Zebrafish) (Brachydanio rerio)
Function: 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 (By similarity). Upon binding of c-di-GMP or cGAMP, STING1 oligomerizes and is able to activate both NF-kappa-B and irf3 transcription pathways 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 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. Exhibits 2',3' phosphodiester linkage-specific ligand recognition: can bind both 2'-3' linked cGAMP and 3'-3' linked cGAMP but is preferentially activated by 2'-3' linked cGAMP (By similarity).
Subcellular location: Endoplasmic reticulum membrane {ECO:0000269|PubMed:23091644}; Multi-pass membrane protein {ECO:0000255}. Cytoplasm, perinuclear region {ECO:0000250|UniProtKB:Q86WV6}. Endoplasmic reticulum-Golgi intermediate compartment membrane {ECO:0000250|UniProtKB:Q86WV6}; Multi-pass membrane protein {ECO:0000255}. Golgi apparatus membrane {ECO:0000250|UniProtKB:Q86WV6}; Multi-pass membrane protein {ECO:0000255}. Cytoplasmic vesicle, autophagosome membrane {ECO:0000250|UniProtKB:Q86WV6}; Multi-pass membrane protein {ECO:0000255}. Note=In response to double-stranded DNA stimulation, translocates from the endoplasmic reticulum through the endoplasmic reticulum-Golgi intermediate compartment and Golgi to post-Golgi vesicles, where the kinase tbk1 is recruited. Upon cGAMP-binding, translocates to the endoplasmic reticulum-Golgi intermediate compartment (ERGIC) in a process that is dependent on COPII vesicles; STING1-containing ERGIC serves as a membrane source for LC3 lipidation, which is a key step in autophagosome biogenesis. {ECO:0000250|UniProtKB:Q86WV6}.
Interaction partners:
- Serine/threonine-protein kinase TBK1
- Inhibitor of nuclear factor kappa B kinase subunit epsilon
- Interferon regulatory factor 3
- Mitochondrial antiviral-signaling protein
- Tripartite motif-containing 13
- Cyclic GMP-AMP synthase
- Interferon regulatory factor 7
Sequence:
MSVMGEDALVPRARSRLPVMCAAGLGFLTLAVAWLLDSDKFSERAGIIAFGLMLERFIYCICLLAEELLFHSRQRYHGRMSEIFRACFRGSGILGMCAIFLMLMLGGVSFSVKQWSHFNLMCAGYMLLNSLGVLGPAPVEISEICEAKKMNVAHGLAWSFYIGYLKFLLPALEVNVREYSRRERLSSPRLHILLPLNARVPSKPEEEDTNVVFHENLPDLKLDRAGVRKRSYTNSVYKITHNNETFSCILEYATPLLTLYQMSQESSAGFGERERKQQVLLFYRTLSQILDNSLECRNRYRLILLNDEHTGDPHYLSRELFQNLKQQDGEIFMDPTNEVHPVPEEGPVGNCNGALQATFHEEPMSDEPTLMFSRPQSLRSEPVETTDYFNPSSAMKQN