Table 2.
Summary of the role of TRIM proteins in innate immunity
| TRIM protein | Mode of action | Cell line | Method |
|---|---|---|---|
| TRIM4 | TRIM4 induces the Lys 63-linked ubiquitination of CARD domain RIG-I, which is crucial for the cytosolic RIG-I signalling pathway | HEK293,THP-1,U937 | Overexpression, RNAi |
| TRIM5 | TRIM5 couples innate viral sensing and CD8+ T-cell activation to increase species barriers against retrovirus infection. | U937,HLA-B*2705-restricted CD8+ T | Overexpression |
| TRIM6 | TRIM6 synthesize unanchored K48-linked poly-ubiquitin chains, which activate IKKε for subsequent STAT1 phosphorylation. | HEK293T,A549,Human DCs | Overexpression, RNAi |
| TRIM11 | TRIM11 inhibits RIG-I-mediated IFNβ production by targeting the TBK1 signaling complex. Interaction is dependent on CC domain of TRIM11 | HEK293, HeLa | Overexpression, RNAi |
| TRIM13 | TRIM13 enhances RIG-I activation and positively regulate signaling pathway | HEK293,A549 | overexpression |
| TRIM13 | TRIM13 regulates the type I IFN response through inhibition of MDA5 activity | HEK293,MEF,L929,BMDM | Knockout, overexpression |
| TRIM14 | TRIM14 interacts with MAVS through its SPRY domain and undergoes k63 linked autoubiquitination and recruits NEMO to the MAVS complex. | HEK293,A549,HeLa | Overexpression, RNAi |
| TRIM21 | The IRF association domain of IRF5 interacts with TRIM21 via its PRY/SPRY domain and mediates its K48 and k63 ubiquitination & regulation. | HEK293T,HEK293-TLR7,TBH-1 | Overexpression |
| TRIM21 | TRIM21 interacts with IRF3 through its SPRY domain and inhibits IRF3 ubiquitination and positively regulates it. | HEK293T, HEK293 | Overexpression, RNAi |
| TRIM21 | TRIM21 acts as a E3 ligase and mediates Monoubiquitination of IKKβ Down-regulates NF-κB Signalling | HEK293T, HEK293, HeLa | Overexpression |
| TRIM21 | TRIM21 interacts with Fc fragment of swine immunoglobulin G (sFc) fused VP1 of FMDV and thereby causing its K48-linked degradation. | PK-15,BHK21,HEK293 | Overexpression |
| TRIM23 | TRIM23 through its ARF domain Interacts with NEMO resulting in its K27-linked ubiquitination and positively regulate downstream pathway | HEK293,HeLa,MEF | Overexpression, RNAi |
| TRIM24 | T-Cell–Intrinsic TRIM24 Is Required for IL-1β–Mediated Activation of TH2 Cells | CD4+ T cells | Knockout, overexpression |
| TRIM25 | TRIM25 induces the Lys 63-linked ubiquitination of CARD domain RIG-I, which is crucial for the cytosolic RIG-I signalling pathway | HEK293T, MEF and Hela | Overexpression, RNAi |
| TRIM25 | Short, Unanchored, K63-Linked Ubiquitin Chains mediated by TRIM25 Activate RIG-I | HEK293T | overexpression |
| TRIM25 | TRIM25 mediates k48 linked polyubiquitination of MAVS and positively regulates IRF3 pathway through regulating oligomerization | HEK293, MEF,HeLa | Overexpression, RNAi |
| TRIM26 | Autoubiquitination of TRIM26 helps TBK1-NEMO interaction, and recruits TBK1 to the MAVS signalsome. | HEK293, THP-1,HeLa, MEF | Overexpression, RNAi |
| TRIM27 | TRIM27 negatively regulates signaling involved in the antiviral response and inflammation by targeting the IKKs | HEK293 | Overexpression, RNAi |
| TRIM27 | TRIM27 mediates K-48 polyubiquitination of PI3KC2β, leading to a decrease in PI3K activity and negatively regulate CD4 T cells | Jurkat-KCa3.1 T, human CD4 T | overexpression, knockout mice |
| TRIM27 | TRIM27 through its SPRY domain interacts with NDB domain of NOD2 and targets it for K48-linked ubiquitination proteasomal degradation | HEK293.HeLa,SW480 | Overexpression, RNAi |
| TRIM28 | TRIM28 acts as a SUMO E3 ligase and negatively regulates IRF7 by SUMOylation | HEK293,HEK293T,A549 | Overexpression, RNAi |
| TRIM29 | TRIM29 induces NEMO ubiquitination through K-48 linkage which results in proteasomal degradation and supression of downstream pathway | MH-S,HEK293 alveolar macrophages | Knockout, overexpression, RNAi |
| TRIM29 | TRIM29 targets STING for K48 ubiquitination and degradation and negatively regulates STING dependent pathway | HEK293, BMDM, MEF,BMDC | Knockout, overexpression, RNAi |
| TRIM30α | TRIM30α interacts with TAK1-TAB2-TAB3 and promotes the k48 linked ubiquitination of degradation of TAB2 and TAB3 thus supressing signaling | J774, HEK293T, HeLa,BMDM | Knockout, overexpression, RNAi |
| TRIM30α | TRIM30α prevents TRAF6 autoubiquitination, diminishes IκBα phosphorylation and negatively regulates the NF-kB pathway | J774, HEK293T, HeLa,BMDM | Knockout, overexpression, RNAi |
| TRIM30α | TRIM30α promotes the degradation of STING via K48-linked ubiquitination and negatively regulates STING dependent pathway | HEK293,MEF,L929,BMDC,D2SC | CRISPR, overexpression, RNAi |
| TRIM30α | TRIM30 negatively regulates NLRP3 inflammasome activation by modulating and inhibiting ROS production | J774, HEK 293T, BMDM | Knockout, overexpression, RNAi |
| TRIM31 | TRIM31 interacted with MAVS and catalyzed the Lys63 (K63)-linked polyubiquitination and regulates downstream pathway positively | HEK293,MEF | Knockout, overexpression, RNAi |
| TRIM31 | TRIM31 directly binds to NLRP3, promotes K48-linked polyubiquitination and proteasomal degradation of NLRP3. | HEK293T,THP-1 | Knockout, overexpression, RNAi |
| TRIM32 | TRIM32 targets STING for K63-linked ubiquitination through its E3 ligase activity, which promoted the interaction of STING with TBK1. | HEK293, THP-1 | Overexpression, RNAi |
| TRIM33 | TRIM33 targets DHX33 for K63 linked ubiquitination which activates the formation of the DHX33-NLRP3 inflammasome complex. | HEK293T,THP-1 | Overexpression, RNAi |
| TRIM38 | TRIM38 interacts with and mediates k48 linked ubiquitination and degradation of TRIF and negatively regulates TLR¾ dependent pathway | BMDM,BMDC | Knockout, overexpression |
| TRIM38 | TRIM38 activates MDA5- and RIG-I through their SUMOylation which enhances dephosphorylation and activation and inhibits its degradation | HEK293,MEF,BMDM | Knockout, overexpression, RNAi |
| TRIM38 | TRIM38 targets NAP1 for ubiquitination and subsequent proteasome-mediated degradation and supresses IFNβ response. | HEK293,HEK293 -TLR¾, RAW cell | Overexpression, RNAi |
| TRIM38 | TRIM38 Interacts with TAB2/3 Through Its PRY-SPRY Domain and mediates k48-linked ubiqutination, degradation and translocation | HEK293,HeLa, | CRISPR, overexpression, RNAi |
| TRIM38 | TRIM38 sumoylates STING during the early phase of viral infection, promoting both STING activation and protein stability | HEK293,HEK293T, MEF | Knockout, overexpression |
| TRIM38 | TRIM38 binds to TRAF6 and promotes its K48-linked polyubiquitination and proteasomal degradation thus supresses downstream pathway | HEK293,RAW cells | Overexpression, RNAi |
| TRIM44 | TRIM44 acts as a deubiquitinase enzyme and prevents k48 linked degradation of MAVS positively regulate MAVS dependent pathway | HEK293,HEK293T,L939,HeLa | Overexpression, RNAi |
| TRIM56 | TRIM56 interacts with TRIF through its C-terminal domain and enhances TLR3 pathway in a E3 ligase independent manner. | HEK293,HEK293-TLR3,Vero,Huh-7.5 | Overexpression, RNAi |
| TRIM56 | TRIM56 interacts with STING and targets it for K63-linked ubiquitination which initiates dimerization and facilitates STING -TBK1 interaction | HEK293,HeLa,human lung fibroblast | Overexpression, RNAi |
| TRIM56 | TRIM56 induces the Lys335 monoubiquitination of cGAS which increases of its dimerization, DNA-binding activity, and cGAMP production. | HEK293T, L929, and Vero | Knockout, overexpression |
| TRIM65 | TRIM65 interacts and promotes K63-linked ubiquitination of MDA5 at lysine 743, which is critical for MDA5 oligomerization and activation. | HEK293, BMDM, MEF HeLa | Overexpression, RNAi |
| TRIM9s | TRIM9s undergoes Lys-63-linked auto-polyubiquitination and serves as a platform to bridge GSK3β to TBK1, activation of IRF3 signaling. | HEK293,A549,THP-1 | Overexpression, RNAi |