cGAS-STING nucleic-acid sensing signaling pathway module

A cGAS or cGAS-like receptor detects cytosolic nucleic acid and synthesises a cyclic-dinucleotide second messenger that activates the ER adaptor STING; activated STING traffics to the ERGIC/Golgi and engages TBK1-family kinase signalling, which drives an innate immune transcriptional output. In vertebrates cGAS senses double-stranded DNA and the output is IRF3-dependent type I interferon; in Drosophila cGLR1 senses double-stranded RNA and the output is the NF-kappaB factor Relish.

Curated compact signaling-pathway module for the cytosolic DNA-sensing cGAS-STING axis, grounded in verified human UniProt exemplar accessions (CGAS Q8N884, STING1 Q86WV6, TBK1 Q9UHD2, IRF3 Q14653), GO molecular-function/process terms confirmed against the cached production GO-CAM gomodel:64c3044100001129, and local PAINT IBD rows for TBK1. The IRF3-centred type I interferon output is the modelled effector branch; STING1's post-Golgi NF-kappaB branch is real but is left as context (see description) rather than modelled as a core step. TBK1 is grounded as a PANTHER family (PTHR22969) with PTN anchors because TBK1's accession appears in the local IBD seed rows; the other members are grounded by verified UniProt exemplar accessions. Animal-spanning exemplars are attached to the deeply conserved roles: the STING receptor and adaptor (PANTHER PTHR34339: human, zebrafish, Drosophila, Pacific oyster, Nematostella and Stylophora coral, i.e. vertebrate through cnidarian) and the cGAS/cGLR cyclic-dinucleotide synthase (PANTHER PTHR10656: human cGAS plus Drosophila, Nematostella and Hydra cGAS-like receptors). Every leaf role has a human representative and a Drosophila representative, either as a family representative member or as a Drosophila variant. The TBK1-family kinase role carries human TBK1 and fly IKKepsilon (dTBK1, FBgn0086657), which is an IBD seed of PAINT node PTN000540338 alongside human TBK1 and is required for dSTING-dependent antiviral gene expression (PMID:34965418); fly IKKbeta also acts downstream of dSTING (PMID:30119996) but is not modelled. The kinase annoton therefore asserts only the shared process (activation of innate immune response) and leaves type I interferon production to the vertebrate IRF3 variant. Two steps have no homologous fly counterpart and are modelled as variant sets instead of forcing a fly gene onto a human function: ligand sensing (vertebrate cGAS binds dsDNA; Drosophila cGLR1 binds dsRNA, and neither fly cGLR carries a DNA-binding annotation) and the effector transcription factor (vertebrate IRF3; Drosophila has no protein with the IRF DNA-binding domain, InterPro IPR001346, and uses the NF-kappaB factor Relish). The output variant set allows more than one branch because vertebrate STING also activates NF-kappaB; that vertebrate NF-kappaB branch is not modelled. All exemplar accessions were taken from the cached InterPro/PANTHER member lists or verified in UniProt. No provider deep-research report was generated for this module; structural claims rest on the GO-CAM models, GO terms, PANTHER families, PAINT rows, and cached papers cited above.