Table 1.
STING interactome
| Interacting protein | STING | Types of regulation | Function | Ref. | ||
|---|---|---|---|---|---|---|
| Protein | No. of TMD | sub-domain for interaction | sub-domain for interaction | |||
| NLRC3 | None | Nucleotide-binding domain | LBD (aa139–344) | − | Blocks STING trafficking and STING–TBK1 association | 251 |
| ZDHHC1 | 4 TM | N terminus of ZDHHC1 (aa1–271) | TMD | + | Promotes the dimerization and aggregation of STING(R232/H232) | 252 |
| BTK | None | SH3/ SH2-interaction domain | TMD | + | BTK Deficiency impairs STING-mediated TBK1 and IRF3 activation | 253 |
| NLRX1 | None | Nucleotide-binding domain | N.D. | − | disrupt STING–TBK1 interaction | 254 |
| iRhom2 | 7 TM | First TMD | TMD | + | Promotes STING–TRAPβ interaction and stabilize STING through depolyubiquitin (K48) | 255 |
| S6K1 | None | Kinase domain | The phosphorylation site | + | Recruits IRF3 to the STING–TBK1 complex for phosphorylation | 256 |
| TRIF | None | CTD | CTD | + | Stabilizes the dimeric form of STING | 257 |
| IFI16 | None | PYRIN domain | N.D. | + | Facilitates recruitment of TBK1 to STING and its phosphorylation of STING | 51 |
| Src | None | SH3 domain | N terminal PXXP motif | + | Promotes the phosphorylation of TBK1 on Tyr179 and TBK1 activation | 258 |
| TMED2 | 1 TM | Lumen GOLD and CC domain | TMD | + | Promotes the Recruitment of STING into the COPII Complex and the trafficking | 259 |
| SNX8 | None | N-terminal domain (aa1–180) | TMD | + | Recruits the VPS34 to STING and promote STING trafficking | 260 |
| UBXN3B | None | UAS domain | N.D. | + | Modulates TRIM56-mediated K63-linked ubiquitination of STING and activation of TBK1 | 261 |
| TMEM203 | 4 TM | N-terminal TMDs | TMD | + | Promotes STING trafficking and Competes for STING Binding with STIM1 | 262 |
| YIPF5 | 5 TM | C-terminal TMDs | TMD | + | Facilitates STING recruitment to COPII in the presence of cytoplasmic dsDNA | 263 |
| STIM1 | 1 TM | Direct interaction of STIM1 | TMD | − | Retains STING at the ER under steady-state conditions | 118 |
| HER2 | None | Intracellular domain | CTD (aa139–379) | − | Recruits AKT1 to phosphorylate TBK1 at S510 and impede STING signalosome assembly | 74 |
| TOLLIP | None | CTD | Short loop between TMD2 and TMD3 | + | Stabilizes STING on the ER under steady-state conditions | 119 |
| STEEP | None | CTD | TMD and dimerization interphase | + | Facilitates PtdIns(3)P production for ER membrane curvature and COPII assembly | 126 |
| Notch | 1 TM | Notch intracellular domain (NICD) | LBD | − | Inhibits STING activation by competing with cGAMP for the CDN-binding site | 264 |
| Galectin-9 | None | Carbohydrate recognition domain 1 | STING | − | Promotes the E3 ubiquitin ligase TRIM29-mediated K48-linked ubiquitination of STING | 265 |
| DAPK3 | None | N.D. | CTD | + | Inhibits STING proteasome-mediated degradation in unstimulated states and promotes STING K63-ubiquitination and STING–TBK1 interaction when activated | 266 |
| REC8 | None | N.D. | The 111–221 section of STING | + | Inhibits the K48-linked ubiquitination (on Lys150 and Lys370) triggered by RNF5 | 267 |
| TMEM120A | 6 TM | CTD | N.D. | + | Promotes STING translocation from the ER to ERGIC and its activation | 268 |
| STX17 | 2 TM | N.D. | CTD | + | Inhibits autophagosomal fusion with lysosomes by sequestering STX17 at ER/ERGIC | 160 |
| UNC93B1 | 12TM | N.D. | N.D. | − | Suppresses STING signaling by targeting STING for lysosome degradation | 269,270 |
| ALG2 | None | N.D. | CTD | − | Inhibits STING trafficking through binding to its C-terminal tail | 271 |
aa amino acid, ALG2 apoptosis-linked gene 2, BTK bruton tyrosine kinase, CDN cyclic dinucleotide, cGAMP cyclic GMP–AMP, CTD C-terminal domain, COPII coat protein complex II, DAPK3 death-associated protein kinase 3, ER endoplasmic reticulum, ERGIC ER–Golgi intermediate compartments, HER2 human epidermal growth factor receptor 2, IFI16 interferon gamma inducible protein 16, IRF3 interferon regulatory factor 3, iRhom2 inactive rhomboid 2, LBD ligand binding domain, N.D. not determined, NLRC3 NLR family caspase recruitment domain containing 3, NLRX1 NLR family member X1, NTD N-terminal domain, REC8 REC8 meiotic recombination protein, RNF5 ring finger protein 5, S6K1 p70 ribosomal protein S6 kinase 1, SNX8 sorting nexin 8, STEEP STING ER exit protein, STIM1 stromal interaction molecule 1, STX17 syntaxin 17, TBK1 TANK-binding kinase 1, TMED2 transmembrane p24 trafficking protein 2, TMEM transmembrane protein, TOLLIP Toll-interacting protein, TRAPβ translocon-associated protein subunit beta; TRIM29, tripartite motif containing-containing protein 29, TRIF TIR domain containing adaptor protein inducing interferon-beta, UBXN3B UBX domain-containing protein 8, UNC93B1 Unc-93 homolog B1, YIPF5 Yip1 domain family member 5, ZDHHC1 zinc finger DHHC-type containing 1, PtdIns (3)P phosphatidylinositol-3-phosphate