TRIM21
TRIM21 (tripartite motif containing 21, also known as Ro52, RO52, RNF81 and SSA1) is a RING-type E3 ubiquitin-protein ligase of the TRIM family. It regulates innate immunity, autophagy and cell cycle progression, and is part of the RoSSA ribonucleoprotein autoantigen. Browse Assay Genie's current range of TRIM21 research reagents below, or read on for the biology behind the target.
TRIM21 is an E3 ubiquitin-protein ligase whose activity depends on the E2 enzymes UBE2D1, UBE2D2, UBE2E1 and UBE2E2. With UBE2D2 it ubiquitinates USP4 and IKBKB, and it also ubiquitinates itself. It is a component of cullin-RING SCF complexes, and a TRIM21-containing SCF(SKP2)-like complex mediates ubiquitination of phosphorylated CDKN1B, promoting its proteasomal degradation. TRIM21 therefore plays a role in cell cycle progression, and it also enhances the decapping activity of DCP2.
In immune signalling, TRIM21 monoubiquitinates IKBKB, which negatively regulates Tax-induced NF-kappa-B signalling. It limits IFN-beta production after pathogen recognition by driving polyubiquitin-mediated degradation of IRF3, and it promotes IRF8 ubiquitination to enhance cytokine gene transcription in macrophages. It also targets the IgG1 heavy chain for proteasomal degradation via the VCP-linked ERAD pathway. Further substrates include NMI, ISG12a/IFI27 and MAVS: Lys-63-linked ubiquitination of NMI represses the antiviral response, Lys-6-linked ubiquitination of ISG12a promotes pyroptosis, and Lys-27-linked ubiquitination of MAVS, when TRIM21 is induced through IFN/JAK/STAT signalling, up-regulates innate immunity.
TRIM21 also organises autophagy. It acts as a platform for assembling ULK1, Beclin 1/BECN1 and ATG8 family members, recognises specific autophagy targets and lowers FIP200/RB1CC1 stability through ubiquitination. In response to heat shock it mediates Lys-63-linked polyubiquitination of G3BP1, leading to stress granule disassembly. The protein belongs to the TRIM/RBCC family, whose motif comprises RING, B-box type 1 and B-box type 2 zinc-binding domains and a coiled-coil region. It is part of the RoSSA ribonucleoprotein particle, a single polypeptide with one of four small RNAs that binds HY RNAs. This particle is found in the cytoplasm and nucleus, and it interacts with autoantigens in patients with Sjogren syndrome and systemic lupus erythematosus, hence the earlier name Sjogren syndrome antigen A1.
TRIM21 modulates IRF3, IRF8, MAVS and NMI through distinct ubiquitin linkages, making it central to studies of antiviral and inflammatory signalling.
TRIM21 assembles ULK1, Beclin 1 and ATG8 family members and recognises autophagy targets, coordinating target recognition with initiation of autophagy.
As part of the RoSSA particle, TRIM21 is an autoantigen in Sjogren syndrome and systemic lupus erythematosus.
TRIM21 works in SCF(SKP2)-like complexes to promote proteasomal degradation of phosphorylated CDKN1B, linking ubiquitination to cell cycle progression.
TRIM21 is an E3 ubiquitin ligase that attaches ubiquitin to substrates including IRF3, IKBKB, CDKN1B, MAVS and G3BP1. Through these targets it regulates innate immune signalling, autophagy, stress granule disassembly and cell cycle progression.
TRIM21 is also called Ro52, RO52, RNF81 and SSA1. The earlier HGNC name was Sjogren syndrome antigen A1 (52kDa, ribonucleoprotein autoantigen SS-A/Ro). Alternatively spliced transcript variants have been described, though the full-length nature of only one has been determined.
TRIM21 is part of the RoSSA ribonucleoprotein, which interacts with autoantigens in patients with Sjogren syndrome and systemic lupus erythematosus. The mouse ortholog is Trim21. Check the datasheet of any product for its validated reactivity.
Other TRIM family E3 ubiquitin ligases involved in immunity, signalling and transcriptional regulation.
Gene and protein annotations from HGNC, NCBI Gene and UniProt P19474; product specifications from Assay Genie datasheets.