TRIM21
GeneName
TRIM21
Summary
TRIM21, also known as SSA, SS A, or Ro52, is a 54 kDa E3 ubiquitin ligase that plays a significant role in the antiviral innate immune response. It is predominantly expressed in the cytoplasm and nucleus, localised to various cellular components including autophagosomes, stress granules, and P-bodies. TRIM21 is involved in multiple biological processes such as the regulation of gene expression, autophagy, and the cellular response to chemical stress. Its functions encompass DNA and RNA binding, transcription coactivator activity, and ubiquitin-protein transferase activity, which enable it to modulate protein stability and activity through ubiquitination and deubiquitination mechanisms.
Importance
TRIM21 is relevant to: - The innate immune response, particularly in the context of viral infections, as it facilitates the recognition and degradation of viral components. - Regulation of autophagy and cellular stress responses, contributing to the maintenance of cellular homeostasis. - Modulation of NF-kappaB signalling pathways, influencing inflammatory responses and immune regulation. - Potential therapeutic target in autoimmune diseases, given its role in the regulation of type I interferon production and viral transcription.
Top Products
For researchers investigating TRIM21, we highly recommend the top-selling recombinant antibody, Anti-TRIM21/SS-A antibody [EPR20290] (ab207728). This antibody has been validated in knockout models, ensuring its reliability in various applications, particularly in Western blotting (WB) and immunohistochemistry (IHC). With 17 citations, it is well-regarded in the research community, demonstrating its effectiveness and trustworthiness for TRIM21 detection. This product is an excellent choice for those seeking consistent and robust results in their studies. The Anti-TRIM21/SS-A antibody ELISA Kit (ab207728), supported by 17 citations, is an excellent option for researchers looking to accurately measure TRIM21 levels in their samples.
Abcam Product Citation Summary
The use of the Abcam antibody ab96800 for TRIM21 detection highlights its application in immunoprecipitation and western blotting, specifically in human polymorphonuclear leukocytes (PMNs). This suggests a focus on immune response or inflammation-related studies involving TRIM21.
Abcam Product Citation Table
Domain
The coiled-coil is necessary for the cytoplasmic localization.
The RING-type zinc finger is necessary for ubiquitination and for the IRF3-driven interferon beta promoter activity. Interacts with SKP2 and CUL1 in a RING finger-independent manner (PubMed:18845142). The RING-type zinc finger is necessary for ubiquitination of NMI (PubMed:26342464).
The B30.2/SPRY domain is necessary for the cytoplasmic localization, the interaction with IRF3 and for the IRF3-driven interferon beta promoter activity (PubMed:18845142). The B30.2/SPRY domain is necessary for the interaction with NMI (PubMed:26342464).
Function
E3 ubiquitin-protein ligase whose activity is dependent on E2 enzymes, UBE2D1, UBE2D2, UBE2E1 and UBE2E2 (PubMed:16297862, PubMed:16316627, PubMed:16472766, PubMed:16880511, PubMed:18022694, PubMed:18361920, PubMed:18641315, PubMed:18845142, PubMed:19675099, PubMed:26347139). Forms a ubiquitin ligase complex in cooperation with the E2 UBE2D2 that is used not only for the ubiquitination of USP4 and IKBKB but also for its self-ubiquitination (PubMed:16880511, PubMed:19675099). Component of cullin-RING-based SCF (SKP1-CUL1-F-box protein) E3 ubiquitin-protein ligase complexes such as SCF(SKP2)-like complexes (PubMed:16880511). A TRIM21-containing SCF(SKP2)-like complex is shown to mediate ubiquitination of CDKN1B ('Thr-187' phosphorylated-form), thereby promoting its degradation by the proteasome (PubMed:16880511). Monoubiquitinates IKBKB that will negatively regulates Tax-induced NF-kappa-B signaling (PubMed:19675099). Negatively regulates IFN-beta production post-pathogen recognition by catalyzing polyubiquitin-mediated degradation of IRF3 (PubMed:18641315). Mediates the ubiquitin-mediated proteasomal degradation of IgG1 heavy chain, which is linked to the VCP-mediated ER-associated degradation (ERAD) pathway (PubMed:18022694). Promotes IRF8 ubiquitination, which enhanced the ability of IRF8 to stimulate cytokine genes transcription in macrophages (By similarity). Plays a role in the regulation of the cell cycle progression (PubMed:16880511). Enhances the decapping activity of DCP2 (PubMed:18361920). Exists as a ribonucleoprotein particle present in all mammalian cells studied and composed of a single polypeptide and one of four small RNA molecules (PubMed:1985094, PubMed:8666824). At least two isoforms are present in nucleated and red blood cells, and tissue specific differences in RO/SSA proteins have been identified (PubMed:8666824). The common feature of these proteins is their ability to bind HY RNAs.2 (PubMed:8666824). Involved in the regulation of innate immunity and the inflammatory response in response to IFNG/IFN-gamma (PubMed:26347139). Organizes autophagic machinery by serving as a platform for the assembly of ULK1, Beclin 1/BECN1 and ATG8 family members and recognizes specific autophagy targets, thus coordinating target recognition with assembly of the autophagic apparatus and initiation of autophagy (PubMed:26347139). Regulates also autophagy through FIP200/RB1CC1 ubiquitination and subsequent decreased protein stability (PubMed:36359729). Represses the innate antiviral response by facilitating the formation of the NMI-IFI35 complex through 'Lys-63'-linked ubiquitination of NMI (PubMed:26342464). During viral infection, promotes cell pyroptosis by mediating 'Lys-6'-linked ubiquitination of ISG12a/IFI27, facilitating its translocation into the mitochondria and subsequent CASP3 activation (PubMed:36426955). When up-regulated through the IFN/JAK/STAT signaling pathway, promotes 'Lys-27'-linked ubiquitination of MAVS, leading to the recruitment of TBK1 and up-regulation of innate immunity (PubMed:29743353). Mediates 'Lys-63'-linked polyubiquitination of G3BP1 in response to heat shock, leading to stress granule disassembly (PubMed:36692217).
Pathway
Protein modification; protein ubiquitination.
Post-translational modifications
Autoubiquitinated; does not lead to its proteasomal degradation. Deubiquitinated by USP4; leading to its stabilization.
Sequence Similarities
Belongs to the TRIM/RBCC family.
Tissue Specificity
Isoform 1 and isoform 2 are expressed in fetal and adult heart and fetal lung.
Cellular localization
- Cytoplasm
- Cytoplasmic vesicle
- Autophagosome
- Nucleus
- Cytoplasm
- P-body
- Cytoplasm
- Stress granule
- Enters the nucleus upon exposure to nitric oxide (PubMed:18361920). Localizes to small dot- or rod-like structures in the cytoplasm, called processing bodies (P-bodies) that are located underneath the plasma membrane and also diffusely in the cytoplasm (PubMed:18361920). They are located along the microtubules and are highly motile in cells (PubMed:18361920). Colocalizes with DCP2 in P-bodies (PubMed:18361920). Localizes to stress granules in response to oxidative stress (PubMed:36692217).
Alternative names
RNF81, RO52, SSA1, TRIM21, E3 ubiquitin-protein ligase TRIM21, 52 kDa Ro protein, 52 kDa ribonucleoprotein autoantigen Ro/SS-A, RING finger protein 81, Ro(SS-A), Sjoegren syndrome type A antigen, Tripartite motif-containing protein 21, SS-A