This entry represents the C-terminal domain in human Tripartite motif-containing protein 2/3 (TRIM2/3)and similar animal proteins. It is formed by NHL repeats ().TRIM2 is a UBE2D1-dependent E3 ubiquitin-protein ligase that mediates the ubiquitination of NEFL and phosphorylated BCL2L11, playing a neuroprotective role and potentially contributing to rapid ischaemic tolerance in neurones. In addition to its role in neuronal health, TRIM2 also participates in antiviral immunity and restricts New World arenavirus infection independently of its ubiquitin ligase activity []. TRIM3, another E3 ubiquitin ligase, is essential for neuronal processes including plasticity, learning, and memory. It functions as part of the cytoskeleton-associated recycling or transport complex in neurones and regulates these processes through the polyubiquitination of gamma-actin and the postsynaptic scaffold GKAP, thereby influencing dendritic spine morphology. Beyond neuronal functions, TRIM3 contributes to innate immunity and cell cycle regulation, promotes TLR3-mediated signalling via Lys-63-linked polyubiquitination, and supports sorting by ESCRT complexes. Additionally, it modulates microtubule motor protein KIF21B and induces growth arrest through RING-dependent E3 ligase activity targeting CDKN1A [].
