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 | |
ZDHHC1 | 4 TM | N terminus of ZDHHC1 (aa1–271) | TMD | + | Promotes the dimerization and aggregation of STING(R232/H232) | |
BTK | None | SH3/ SH2-interaction domain | TMD | + | BTK Deficiency impairs STING-mediated TBK1 and IRF3 activation | |
NLRX1 | None | Nucleotide-binding domain | N.D. | − | disrupt STING–TBK1 interaction | |
iRhom2 | 7 TM | First TMD | TMD | + | Promotes STING–TRAPβ interaction and stabilize STING through depolyubiquitin (K48) | |
S6K1 | None | Kinase domain | The phosphorylation site | + | Recruits IRF3 to the STING–TBK1 complex for phosphorylation | |
TRIF | None | CTD | CTD | + | Stabilizes the dimeric form of STING | |
IFI16 | None | PYRIN domain | N.D. | + | Facilitates recruitment of TBK1 to STING and its phosphorylation of STING | |
Src | None | SH3 domain | N terminal PXXP motif | + | Promotes the phosphorylation of TBK1 on Tyr179 and TBK1 activation | |
TMED2 | 1 TM | Lumen GOLD and CC domain | TMD | + | Promotes the Recruitment of STING into the COPII Complex and the trafficking | |
SNX8 | None | N-terminal domain (aa1–180) | TMD | + | Recruits the VPS34 to STING and promote STING trafficking | |
UBXN3B | None | UAS domain | N.D. | + | Modulates TRIM56-mediated K63-linked ubiquitination of STING and activation of TBK1 | |
TMEM203 | 4 TM | N-terminal TMDs | TMD | + | Promotes STING trafficking and Competes for STING Binding with STIM1 | |
YIPF5 | 5 TM | C-terminal TMDs | TMD | + | Facilitates STING recruitment to COPII in the presence of cytoplasmic dsDNA | |
STIM1 | 1 TM | Direct interaction of STIM1 | TMD | − | Retains STING at the ER under steady-state conditions | |
HER2 | None | Intracellular domain | CTD (aa139–379) | − | Recruits AKT1 to phosphorylate TBK1 at S510 and impede STING signalosome assembly | |
TOLLIP | None | CTD | Short loop between TMD2 and TMD3 | + | Stabilizes STING on the ER under steady-state conditions | |
STEEP | None | CTD | TMD and dimerization interphase | + | Facilitates PtdIns(3)P production for ER membrane curvature and COPII assembly | |
Notch | 1 TM | Notch intracellular domain (NICD) | LBD | − | Inhibits STING activation by competing with cGAMP for the CDN-binding site | |
Galectin-9 | None | Carbohydrate recognition domain 1 | STING | − | Promotes the E3 ubiquitin ligase TRIM29-mediated K48-linked ubiquitination of STING | |
DAPK3 | None | N.D. | CTD | + | Inhibits STING proteasome-mediated degradation in unstimulated states and promotes STING K63-ubiquitination and STING–TBK1 interaction when activated | |
REC8 | None | N.D. | The 111–221 section of STING | + | Inhibits the K48-linked ubiquitination (on Lys150 and Lys370) triggered by RNF5 | |
TMEM120A | 6 TM | CTD | N.D. | + | Promotes STING translocation from the ER to ERGIC and its activation | |
STX17 | 2 TM | N.D. | CTD | + | Inhibits autophagosomal fusion with lysosomes by sequestering STX17 at ER/ERGIC | |
UNC93B1 | 12TM | N.D. | N.D. | − | Suppresses STING signaling by targeting STING for lysosome degradation | |
ALG2 | None | N.D. | CTD | − | Inhibits STING trafficking through binding to its C-terminal tail | |
