E3 ubiquitin-protein ligase RNF128 (RNF128)

E3 ubiquitin-protein ligase RNF128 (commonly known as GRAIL) is a type I transmembrane enzyme characterized by a RING zinc finger motif and protease-associated (PA) domain, enabling its E3 ubiquitin ligase activity[1][6]. RNF128 is central to the induction and maintenance of T cell anergy by ubiquitinating key surface proteins (such as CD151, CD81, CD40L, CD83) and intracellular substrates, which modulates immune responses and protein homeostasis[1][3][6]. It is also a positive regulator of innate antiviral immunity through activating TBK1 via K63-linked ubiquitination, which stimulates interferon-β (IFN-β) production essential for antiviral defense[2][4]. RNF128 has been implicated in cancer progression (notably melanoma) and other pathologies through its diverse substrate interactions and regulatory roles in immunity, cytoskeleton, cytokine signaling, and N-glycosylation[1][3][7]. Alternative names include GRAIL, ring finger protein 128, and gene related to anergy in lymphocytes protein. No direct pharmacological modulators or clinical drugs are currently reported to interact with RNF128, but its roles suggest therapeutic potential in immunity and oncology.

Other names

GRAILring finger protein 128gene related to anergy in lymphocytes proteinFLJ23516RING-type E3 ubiquitin transferase RNF128

Catalyzes Lys-27, Lys-48, and Lys-63–linked polyubiquitin chains on substrate proteins, targeting them for proteasomal degradation or altering their signaling activity. K63-linked polyubiquitination of TBK1, activating innate immune signaling (stimulating IFN-β production). Ubiquitination of proteins like CD151, CD81, ARPC5, COR1A, CD40L, CD83, IL3RA, RPN1, and others, modulating immune and cellular homeostasis.