UVRAGcontaining

UVRAGcontaining refers to protein assemblies or complexes that include the UVRAG protein, most notably the class III phosphatidylinositol 3-kinase (PI3K) complex that also contains VPS34 and Beclin-1. In humans, UVRAG (UV radiation resistance–associated gene) acts as a Beclin-1–binding partner and helps regulate autophagy and endosomal trafficking. The term is often used to distinguish UVRAG-containing complexes from other Beclin-1–associated PI3K complexes, such as the ATG14L-containing complex; both share core components but differ in regulatory subunits that bias their cellular roles.

Functionally, the UVRAG-containing complex contributes to autophagosome maturation and endosome-to-lysosome trafficking by promoting the production of phosphatidylinositol 3-phosphate on endosomal membranes, which helps recruit effector proteins required for vesicle maturation and cargo sorting. This activity supports the proper progression of autophagy beyond initiation and is important for maintaining cellular homeostasis through vesicular trafficking.

Regulation and context-dependent roles are characteristic of UVRAG-containing complexes. UVRAG activity is modulated by cellular signaling, and its association with Beclin-1 and VPS34 can be influenced by phosphorylation and other post-translational modifications. In addition to autophagy-related functions, UVRAG has been reported to participate in DNA damage response pathways in some contexts, including interactions with BRCA1, linking autophagy regulation to genome stability.

Clinical and research interest in UVRAG-containing complexes centers on their roles in cancer and neurodegenerative diseases, where alterations in autophagy and endolysosomal trafficking can impact disease progression. The precise outcomes of UVRAG-containing signaling are context-dependent and continue to be explored.