UVRAG
Description
The UVRAG (UV radiation resistance associated) is a protein-coding gene located on chromosome 11.
UVRAG (UV radiation resistance-associated gene protein) is a protein encoded by the UVRAG gene in humans. It complements the ultraviolet sensitivity of xeroderma pigmentosum group C cells and contains a C2 domain. The protein activates the Beclin1-PI(3)KC3 complex, promoting autophagy and suppressing the proliferation and tumorigenicity of human colon cancer cells. Chromosomal aberrations involving this gene are associated with left-right axis malformation, and mutations in this gene have been associated with colon cancer.
UVRAG is a versatile protein involved in regulating various cellular pathways related to membrane trafficking. It plays a role in the COPI-dependent retrograde transport from the Golgi and endoplasmic reticulum by associating with the NRZ complex, a process dependent on its binding to phosphatidylinositol 3-phosphate (PtdIns(3)P). During autophagy, UVRAG acts as a regulatory subunit of the alternative PI3K complex II (PI3KC3-C2) which mediates the formation of phosphatidylinositol 3-phosphate. This complex is believed to be involved in autophagosome maturation and endocytosis. UVRAG activates the lipid kinase activity of PIK3C3, further supporting its role in autophagy and endocytic trafficking. Additionally, UVRAG contributes to the regulation of degradative endocytic trafficking and cytokinesis, as well as the regulation of ATG9A transport from the Golgi to the autophagosome. These functions are likely linked to its association with the PI3KC3-C2 complex. UVRAG is also involved in the maturation of autophagosomes and degradative endocytic trafficking independent of BECN1, but dependent on its association with a class C Vps complex, potentially the HOPS complex. This association promotes autophagosome recruitment, activation of Rab7, and endosome-endosome fusion events. UVRAG enhances the association of the class C Vps complex (possibly the HOPS complex) with a SNARE complex, promoting the formation of a fusogenic SNARE complex during late endocytic membrane fusion. During negative-strand RNA virus infection, UVRAG is required for efficient virus entry, promotes the endocytic transport of virions, and is implicated in the assembly of a VAMP8-specific fusogenic SNARE complex.
UVRAG is also known as DHTX, VPS38, p63.
