Transmembrane protein 129, E3 ubiquitin ligase (TMEM129)

Transmembrane protein 129, E3 ubiquitin ligase (TMEM129) is a tri-spanning, ER-resident membrane protein with a cytosolic C-terminal RING-type E3 ubiquitin ligase domain. TMEM129 promotes the ubiquitination and subsequent degradation of ER-associated misfolded secretory proteins as part of the ER-associated degradation (ERAD) pathway[1][2][4]. Its E3 activity is key for tagging target substrates with ubiquitin for proteasomal degradation, and it uniquely features a “cysteine-only” RING domain[2][4][5]. TMEM129 is essential for the US11-mediated degradation of MHC class I molecules, a mechanism hijacked by human cytomegalovirus to evade immune responses[1][2][4][5]. It acts in complex with ERAD components such as Derlin-1 and the E2 conjugase Ube2J2[2][5]. TMEM129 deficiency blocks US11-induced MHC class I loss and thus impairs this aspect of viral immune evasion[2][4]. No interacting drugs or established clinical biomarkers are currently reported in the literature.

Other names

E3 ubiquitin-protein ligase TM129D4S2561ERING-type E3 ubiquitin transferase TM129transmembrane protein 129E3 ubiquitin protein ligase