PSMD14

Component of the 26S proteasome, a multiprotein complex involved in the ATP-dependent degradation of ubiquitinated proteins. This complex plays a key role in the maintenance of protein homeostasis by removing misfolded or damaged proteins, which could impair cellular functions, and by removing proteins whose functions are no longer required. Therefore, the proteasome participates in numerous cellular processes, including cell cycle progression, apoptosis, or DNA damage repair. The PSMD14 subunit is a metalloprotease that specifically cleaves 'Lys-63'-linked polyubiquitin chains within the complex. Plays a role in response to double-strand breaks (DSBs): acts as a regulator of non-homologous end joining (NHEJ) by cleaving 'Lys-63'-linked polyubiquitin, thereby promoting retention of JMJD2A/KDM4A on chromatin and restricting TP53BP1 accumulation. Also involved in homologous recombination repair by promoting RAD51 loading. Regulates macroautophagy by ensuring Golgi-to-ER retrograde transport through its deubiquitinating activity on K63-linked ubiquitin chains. This activity prevents the retention of essential autophagy proteins at the Golgi, enabling their trafficking to autophagosome formation sites and supporting Golgi-ER membrane recycling critical for effective autophagy..

Function from UniProtKB (O00487), read 2026-09-23. CC BY 4.0.