E3 ubiquitin-protein ligase TRIM21 (TRIM21)

E3 ubiquitin-protein ligase TRIM21 (TRIM21) is a member of the TRIM (tripartite motif) protein family, characterized by the presence of a RING domain (responsible for its E3 ubiquitin ligase activity), B-box motifs, a coiled-coil region, and a C-terminal PRY/SPRY domain. TRIM21 is a distinctive cytosolic Fc receptor that binds to the Fc region of antibodies and plays a central role in *intracellular immunity*: when antibody-coated pathogens are internalized into the cytosol, TRIM21 recognizes them and triggers their rapid degradation through the ubiquitin-proteasome system, a process termed antibody-dependent intracellular neutralization. Beyond antiviral defense, TRIM21 functions in the regulation of immune signaling and is a major autoantigen in several systemic autoimmune diseases, notably Sjögren’s syndrome, systemic lupus erythematosus, and rheumatoid arthritis. The presence of anti-TRIM21 (anti-Ro52) autoantibodies is used diagnostically in these conditions. TRIM21 is being explored as a tool for selective degradation of intracellular proteins (Trim-Away technology) for research and therapeutic purposes[1][2][3][4].

Other names

Ro52SSA1SS-ARNF8152 kDa Ro protein52 kDa ribonucleoprotein autoantigen Ro/SS-ARING finger protein 81Ro(SS-A)Sjoegren syndrome type A antigenTripartite motif-containing protein 21Ro/SSA 52kDaSicca syndrome antigen ASjogren syndrome antigen A1ro(SS-A)sjoegren syndrome type A antigen

Polyubiquitination leading to proteasomal degradation of antibody-bound targets (antibody-dependent intracellular neutralization[2]); Modulation of innate immune pathways via ubiquitination-dependent signaling