Protein: Stimulator of interferon genes protein (STING) (Transmembrane protein 173) (E1C7U0)
Organism: Gallus gallus (Chicken)
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) (By similarity). Innate immune response is triggered in response to non-CpG double-stranded DNA from viruses and bacteria delivered to the cytoplasm (By similarity). 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, 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 (By similarity). Following cGAMP-binding, STING1 buds from the endoplasmic reticulum into COPII vesicles, which then form the endoplasmic reticulum-Golgi intermediate compartment (ERGIC) (By similarity). 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 (By similarity). The autophagy- and interferon-inducing activities can be uncoupled and autophagy induction is independent of TBK1 phosphorylation (By similarity). 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:0000250|UniProtKB:Q86WV6}; 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}.
Sequence: MPQDPSTRSSPARLLIPEPRAGRARHAACVLLAVCFVVLFLSGEPLAPIIRSVCTQLAALQLGVLLKGCCCLAEEIFHLHSRHHGSLWQVLCSCFPPRWYLALLLVGGSAYLDPPEDNGHSPRLALTLSCLCQLLVLALGLQKLSAVEVSELTESSKKNVAHGLAWSYYIGYLKVVLPRLKECMEELSRTNPMLRAHRDTWKLHILVPLGCDIWDDLEKADSNIQYLADLPETILTRAGIKRRVYKHSLYVIRDKDNKLRPCVLEFASPLQTLCAMSQDDCAAFSREQRLEQARLFYRSLRDILGSSKECAGLYRLIAYEEPAEPESHFLSGLILWHLQQQQREEYMVQEELPLGTSSVELSLQVSSSDLPQPLRSDCP
InterPro domains: - IPR055434: STING, transmembrane domain (domain) [51-157]
- IPR029158: Stimulator of interferon genes protein (family) [10-353]
- IPR055432: STING, ligand-binding domain (domain) [159-342]
- IPR038623: Stimulator of interferon genes protein, C-terminal domain superfamily (homologous_superfamily) [200-346]
- IPR047191: Stimulator of interferon genes protein, C-terminal (domain) [159-342]
Interaction partners: - Serine/threonine-protein kinase TBK1
- Inhibitor of nuclear factor kappa B kinase subunit epsilon.
- CARD_2 domain-containing protein.
- Cyclic GMP-AMP synthase.
- Interferon regulatory factor 3
- Uncharacterized protein.
Gene Ontology annotations:
Molecular Function (MF): GO:0003674 (molecular function), GO:0005488 (binding), GO:0036094 (small molecule binding), GO:1901363 (heterocyclic compound binding), GO:0097159 (organic cyclic compound binding), GO:0043167 (ion binding), GO:0097367 (carbohydrate derivative binding), GO:1901265 (nucleoside phosphate binding), GO:0043168 (anion binding), GO:0000166 (nucleotide binding), GO:0032553 (ribonucleotide binding), GO:0030551 (cyclic nucleotide binding), GO:0032555 (purine ribonucleotide binding), GO:0017076 (purine nucleotide binding), GO:0019001 (guanyl nucleotide binding), GO:0032559 (adenyl ribonucleotide binding), GO:0032561 (guanyl ribonucleotide binding), GO:0030554 (adenyl nucleotide binding)
Biological Process (BP): GO:0008150 (biological process), GO:0009987 (cellular process), GO:0065007 (biological regulation), GO:0048518 (positive regulation of biological process), GO:0050896 (response to stimulus), GO:0050789 (regulation of biological process), GO:0009893 (positive regulation of metabolic process), GO:0051716 (cellular response to stimulus), GO:0051239 (regulation of multicellular organismal process), GO:0042221 (response to chemical), GO:0019222 (regulation of metabolic process), GO:0051240 (positive regulation of multicellular organismal process), GO:0060255 (regulation of macromolecule metabolic process), GO:0001819 (positive regulation of cytokine production), GO:0001817 (regulation of cytokine production), GO:0010604 (positive regulation of macromolecule metabolic process), GO:0010033 (response to organic substance), GO:0070887 (cellular response to chemical stimulus), GO:0010628 (positive regulation of gene expression), GO:0014070 (response to organic cyclic compound), GO:0032481 (positive regulation of type I interferon production), GO:0071310 (cellular response to organic substance), GO:0010468 (regulation of gene expression), GO:0032479 (regulation of type I interferon production), GO:0071407 (cellular response to organic cyclic compound)
Cellular Component (CC): GO:0005575 (cellular component), GO:0110165 (cellular anatomical entity), GO:0005622 (intracellular anatomical structure), GO:0043226 (organelle), GO:0005737 (cytoplasm), GO:0012505 (endomembrane system), GO:0043229 (intracellular organelle), GO:0005783 (endoplasmic reticulum), GO:0043227 (membrane-bounded organelle), GO:0043231 (intracellular membrane-bounded organelle)