- RNF115, also known as Breast Cancer–Associated Gene 2 (BCA2), is a multifunctional E3 ubiquitin ligase that contains both a RING finger domain and a U‑box–like structural fold, enabling it to participate in diverse ubiquitin‑signalling pathways. RNF115 is primarily localised to the plasma membrane, endosomal compartments and the Golgi, where it regulates membrane trafficking, immune signalling and protein turnover.
- RNF115 functions through a RING‑type mechanism, binding an E2 ubiquitin‑conjugating enzyme and facilitating direct ubiquitin transfer to substrate lysines. Its activity is strongly influenced by cellular localisation, phosphorylation state and interaction with adaptor proteins. RNF115 is known to assemble K48‑linked chains for proteasomal degradation and K63‑linked chains for non‑degradative signalling, giving it flexibility in shaping downstream pathways.
- One of the most studied roles of RNF115 is in innate immune signalling. It regulates TLR (Toll‑like receptor) pathways, modulating NF‑κB activation and cytokine production. RNF115 also ubiquitinates components of the endosomal sorting machinery, influencing receptor internalisation and trafficking. In cancer biology, RNF115 is frequently overexpressed in breast tumours, where it affects cell migration, proliferation and membrane‑associated signalling networks.
- RNF115 interacts with proteins such as Rab7, Tetherin/BST‑2, and EGFR, linking it to vesicular transport, antiviral defence and receptor turnover. Its antiviral role is particularly notable: RNF115 ubiquitinates BST‑2, modulating viral budding and release. This positions RNF115 at the interface between membrane trafficking and host defence.
- Mutations or dysregulation of RNF115 have been associated with altered immune responses, tumour progression and defects in membrane‑protein homeostasis. Because of its dual RING/U‑box structural features and broad substrate range, RNF115 is increasingly recognised as a potential therapeutic target in oncology and immunology.
