Drosophila melanogaster Sting (dSTING, CG1667, FBgn0033453; UniProt A0A0B4LFY9) — curation notes

Provenance

Automated deep research (just deep-research DROME Sting --provider perplexity) failed in this
environment (agentapi not found in PATH, no provider configured), so no -deep-research-<provider>.md
file was generated. These notes are compiled manually from the cached publications in publications/
and the UniProt record. All assertions carry inline PMID provenance with verbatim supporting text.

Summary of gene function

dSTING is the single Drosophila ortholog of the STING family (STING_LBD + STING_TM domains;
IPR029158). It is a multi-pass endoplasmic reticulum membrane protein (343 aa) that functions as an
innate-immune signaling adapter. Unlike vertebrate STING, the fly (and insects generally) have no
type I interferon system and no TBK1->IRF3->IFN axis; dSTING instead signals to the NF-kappaB
transcription factor Relish through the IMD pathway (via the kinase dIKKbeta), driving
antimicrobial peptide (AMP) and antiviral gene expression.

Ligand recognition (molecular function)

• Binds bacterial cyclic di-GMP (c-di-GMP): PMID:29924997
• Binds the virus-induced CDNs 3'2'-cGAMP (strongly preferred) and 2'3'-cGAMP, produced by the cGAS-like receptors cGLR1/cGLR2 in response to (ds)RNA virus: PMID:34261127 and PMID:34261128
• A crystal structure of dSTING bound to 3'2'-cGAMP explains isomer selectivity: PMID:34261127
• Also responds to the virus-induced CDN 2'3'-c-di-GMP, a more potent dSTING agonist than cGAMP: PMID:37659413

Antibacterial function

• Activates AMP production and defense against Listeria monocytogenes via Relish/IMD: PMID:29924997 and PMID:29924997
• Protects against the Gram-negative bacterium Coxiella burnetii by limiting reactive oxygen species: PMID:38363133

Antiviral function (NF-kappaB / Relish, interferon-independent)

• Controls picorna-like viruses downstream of the cGLR sensors, acting upstream of dIKKbeta to induce the antiviral factor Nazo: PMID:30119996
• 2'3'-cGAMP triggers a Relish (NF-kB)-dependent, interferon-independent antiviral program: PMID:33262294
• Orally acquired bacterial CDNs drive dSTING/dTBK1-dependent, NF-kB-dependent antiviral immunity in gut enterocytes: PMID:34965418
• A cryptic RHIM (cRHIM) motif drives dSTING oligomerization and antiviral signaling and its interaction with IMD: PMID:38969190

Autophagy (interferon-independent, context-specific)

• In the adult brain, Zika-virus-induced NF-kB signaling induces dSTING, which restricts infection by inducing autophagy: PMID:29934091

Localization

• Endoplasmic reticulum membrane, multi-pass membrane protein: PMID:30119996 (UniProt SUBCELLULAR LOCATION: "Endoplasmic reticulum membrane {ECO:0000269|PubMed:30119996}").

Curation implications

• The IEA GO:0032481 positive regulation of type I interferon production (InterPro2GO from IPR029158)
  is taxonomically inappropriate for Drosophila, which has no type I interferons. dSTING signals to
  NF-kB/Relish, not IFN. This is a demonstrably wrong electronic mapping and is removed.
• Autophagy / autophagosome / reticulophagy terms reflect the ancestral STING autophagy function
  (mammalian Q86WV6) transferred by IBA; the fly has a real but context-specific (Zika brain) autophagy
  role — retained as non-core where they are inherited/component terms.
• Core functions are cyclic-dinucleotide binding (c-di-GMP, 3'2'-cGAMP, 2'3'-cGAMP) driving the
  cGAS/STING signaling pathway to NF-kB (Relish), producing antibacterial and antiviral innate immune
  responses, at the ER membrane.