Table 2.
Post-translational modifications of proteins in cytosolic RNA sensing signaling pathways.
| Protein | Post-translational modification | Modifying enzyme | Modification site(s) | Function | Reference |
|---|---|---|---|---|---|
| RIG-I | Ubiquitination | Unanchored chains (K63-linked) | RIG-I activation by binding RIG-I CARD domains | (121) | |
| Ubiquitination | TRIM25/EFP | hK172 | RIG-I activation | (122) | |
| Ubiquitination | Riplet | (K63-linked) | RIG-I activation | (123) | |
| Ubiquitination | RNF 135 | hK849/851 (K63-linked) | RIG-I activation | (124) | |
| Ubiquitination | REUL | hK154/164/172 (K63-linked) | RIG-I activation | (125) | |
| Ubiquitination | TRIM4 | hK154/164/172 (K63-linked) | RIG-I activation | (126) | |
| Ubiquitination | MEX3C | hK99/169 (K63-linked) | RIG-I activation | (127) | |
| Ubiquitination | RNF122 | hK115/146 (K48-linked) | RIG-I degradation | (128) | |
| Ubiquitination | RNF125 | (K48-linked) | RIG-I degradation | (129) | |
| Ubiquitination | HOIL-1L/HOIP LUBAC | TRIM25 degradation and RIG-I K63 ubiquitination inhibition | (130) | ||
| Ubiquitination | c-Cbl | hK813 (K48-linked) | Siglec-G induced by RNA viral infection facilitates SHP2 and c-Cbl binding and degradation of RIG-I | (131) | |
| Deubiquitination | CYLD | (K63-linked) | RIG-I inhibition | (132) | |
| Deubiquitination | USP3 | (K63-linked) | RIG-I inhibition (K63-linked ubiquitin chain removal upon viral infection) | (133) | |
| Deubiquitination | USP21 | (K63-linked) | RIG-I inhibition (K63-linked ubiquitin chain removal) | (134) | |
| Deubiquitination | USP4 | (K48-linked) | Facilitates RIG-I activation by removing K48-linked ubiquitination | (135) | |
| Deubiquitination | USP15 | Deubiquitylates and stabilizes TRIM25 to enhance TRIM25-mediated RIG-I ubiquitination and activation | (136) | ||
| Phosphorylation | hT170 | RIG-I inhibition via inhibiting K172 polyubiquitination | (137) | ||
| Phosphorylation | hS8 | RIG-I inhibition by inhibiting TRIM25 induced RIG-I ubiquitination | (138) | ||
| Phosphorylation | PKC-α/β | hS8 and T170 | RIG-I inhibition by inhibiting RIG-I binding with TRIM25 and MAVS | (139) | |
| Phosphorylation | CKII | hT770/S854/S855 | RIG-I inhibition by inhibiting RIG-I multimerization | (140) | |
| Dephosphorylation | PP1α and PP1γ | hS8 and T170 | RIG-I activation | (141, 142) | |
| SUMO | TRIM38 | hK96/K888 | RIG-I activation | (143) | |
| SUMO | SENP2 | RIG-I inhibition | (143) | ||
| Deamidation | PFAS | hQ10/N245/N445 | RIG-I activation | (144) | |
| Deacetylation | HDAC6 | hK909 | RIG-I oligomerization and activation | (145, 146) | |
| MDA5 | Ubiquitination | RNF125 | (K48-linked) | MDA5 degradation | (129) |
| Ubiquitination | TRIM13 | (K48-linked) | MDA5 degradation | (147) | |
| Deubiquitination | USP3 | (K63-linked) | MDA5 inhibition | (133) | |
| Ubiquitination | TRIM65 | hK743 (K63-linked) | MDA5 oligomerization and activation | (148) | |
| Dephosphorylation | PP1 | hS88 | MDA5 activation | (141) | |
| Phosphorylation | RIOK3 | hS828 | MDA5 inhibition by impairing multimer formation | (149) | |
| SUMO | TRIM38 | hK43/K865 | MDA5 stabilization and activation | (143) | |
| SUMO | SENP2 | MDA5 degradation and inhibition | (143) | ||
| ISGylation | MDA5 oligomerization and activation and is antagonized by papain-like protease of SARS-CoV-2 | (150) | |||
| MAVS | Ubiquitination | TRIM31 | hK10/K311/K461 (K63-linked) | MAVS oligomerization and activation | (151) |
| Deubiquitination | USP18 | MAVS activation by recruiting TRIM31 | (152) | ||
| Ubiquitination | TRIM21 | hK325 (K27-linked) | MAVS activation to recruit TBK1 | (153) | |
| O-GlcNAcylation | OGT | hS366 | MAVS activation by enhancing K63-linked ubiquitination | (154) | |
| Deubiquitination | OTUD4 | (K48-linked) | MAVS stabilization | (155) | |
| Ubiquitination | TRIM25 | hK7/K10 (K48-linked) | MAVS degradation and release of MAVS assembled signaling complex for IRF3 activation | (156) | |
| Ubiquitination | YOD1 | (K63-linked) | Removes K63-linked ubiquitin from MAVS and reduces MAVS aggregates | (157) | |
| Deubiquitination | OTUD3 | (K63-linked) | MAVS inhibition | (158) | |
| Ubiquitination | AIP4 | hK371/K420 (K48-linked) | Bridged by PCBP1/PCPB2 to target MAVS for degradation | (159, 160) | |
| Ubiquitination | RNF115 | hK500 (K48-linked) | MAVS degradation | (88) | |
| Ubiquitination | pVHL | hK420 (K48-linked) | MAVS degradation | (161) | |
| Ubiquitination | MARCH5 | hK193/K203 and/or hK7/K500 (K48-linked) | MAVS degradation | (162) (163) | |
| Ubiquitination | Itch | (K48-linked) | MAVS degradation mediated by TAX1BP1 | (164) | |
| Ubiquitination | Smurf2 | MAVS degradation | (165) | ||
| Ubiquitination | Smurf1 | (K48-linked) | MAVS degradation mediated by Ndfip1 | (166) | |
| Deubiquitination | OTUD1 | MAVS degradation by stabilizing Smurf1 to promote Smurf1-mediated MAVS ubiquitination | (167) | ||
| Ubiquitination | RNF5 | hK362/K461 (K48-linked) | MAVS degradation | (168) | |
| Ubiquitination | STUB1 | MAVS degradation mediated by RACK1 after BEFV infection | (169) | ||
| Phosphorylation | TBK1/IKKβ | hS442 | MAVS activation to recruit IRF3 | (81) | |
| Phosphorylation | cAbl | MAVS activation | (170) | ||
| Phosphorylation | NLK | hS121/S212/S258/S329 | MAVS degradation and inhibition | (171) | |
| Dephosphorylation | PPM1A | MAVS dephosphorylation and inhibition | (172) | ||
| SUMOylation | SUMO3 but not SUMO1/SUMO2 | MAVS aggregation enhanced | (173) | ||
| Desuccinylation | SIRT5 | hK7 | MAVS aggregation reduced upon desuccinylation | (174) |
The orange color indicates activation of the indicated molecule by indicated modifications; the blue color indicates suppression of the indicated molecules by indicated modifications.