UVRAG

This gene complements the ultraviolet sensitivity of xeroderma pigmentosum group C cells and encodes a protein with 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. [provided by RefSeq, Jul 2008]

Full Name

UV Radiation Resistance Associated

Function

Versatile protein that is involved in regulation of different cellular pathways implicated in membrane trafficking. Involved in regulation of the COPI-dependent retrograde transport from Golgi and the endoplasmic reticulum by associating with the NRZ complex; the function is dependent on its binding to phosphatidylinositol 3-phosphate (PtdIns3P) (PubMed:16799551, PubMed:18552835, PubMed:20643123, PubMed:24056303, PubMed:28306502).
During autophagy acts as regulatory subunit of the alternative PI3K complex II (PI3KC3-C2) that mediates formation of phosphatidylinositol 3-phosphate and is believed to be involved in maturation of autophagosomes and endocytosis. Activates lipid kinase activity of PIK3C3 (PubMed:16799551, PubMed:20643123, PubMed:24056303, PubMed:28306502).
Involved in the regulation of degradative endocytic trafficking and cytokinesis, and in regulation of ATG9A transport from the Golgi to the autophagosome; the functions seems to implicate its association with PI3KC3-C2 (PubMed:16799551, PubMed:20643123, PubMed:24056303).
Involved in maturation of autophagosomes and degradative endocytic trafficking independently of BECN1 but depending on its association with a class C Vps complex (possibly the HOPS complex); the association is also proposed to promote autophagosome recruitment and activation of Rab7 and endosome-endosome fusion events (PubMed:18552835, PubMed:28306502).
Enhances class C Vps complex (possibly HOPS complex) association with a SNARE complex and promotes fusogenic SNARE complex formation during late endocytic membrane fusion (PubMed:24550300).
In case of negative-strand RNA virus infection is required for efficient virus entry, promotes endocytic transport of virions and is implicated in a VAMP8-specific fusogenic SNARE complex assembly (PubMed:24550300).
Involved in maintaining chromosomal stability. Promotes DNA double-strand break (DSB) repair by association with DNA-dependent protein kinase complex DNA-PK and activating it in non-homologous end joining (NHEJ) (PubMed:22542840).
Required for centrosome stability and proper chromosome segregation (PubMed:22542840).

Biological Process

Biological Process autophagosome maturation Source:UniProtKB1 Publication
Biological Process autophagy Source:CACAO1 Publication
Biological Process centrosome cycle Source:UniProtKB1 Publication
Biological Process chromosome segregation Source:Ensembl
Biological Process DNA repair Source:UniProtKB1 Publication
Biological Process double-strand break repair via classical nonhomologous end joining Source:UniProtKB1 Publication
Biological Process maintenance of Golgi location Source:CACAO1 Publication
Biological Process multivesicular body sorting pathway Source:ParkinsonsUK-UCL1 Publication
Biological Process phosphatidylinositol-3-phosphate biosynthetic process Source:ComplexPortal1 Publication
Biological Process positive regulation of autophagosome maturation Source:ParkinsonsUK-UCL1 Publication
Biological Process protein phosphorylation Source:ComplexPortal1 Publication
Biological Process receptor catabolic process Source:UniProtKB1 Publication
Biological Process regulation of autophagy Source:ComplexPortal1 Publication
Biological Process regulation of cytokinesis Source:UniProtKB1 Publication
Biological Process regulation of protein serine/threonine kinase activity Source:UniProtKB1 Publication
Biological Process retrograde vesicle-mediated transport, Golgi to endoplasmic reticulum Source:CACAO1 Publication
Biological Process SNARE complex assembly Source:GO_Central1 Publication
Biological Process spindle organization Source:Ensembl
Biological Process viral entry into host cell Source:Ensembl

Cellular Location

Late endosome
Lysosome
Cytoplasmic vesicle, autophagosome
Early endosome
Endoplasmic reticulum
Midbody
Chromosome, centromere
Colocalizes with RAB9-positive compartments involved in retrograde transport from late endosomes to trans-Golgi network. Colocalization with early endosomes is only partial (PubMed:24056303).
Recruited to autophagosome following interaction with RUBCNL/PACER (PubMed:28306502).

Involvement in disease

A chromosomal aberration involving UVRAG has been observed in a patient with heterotaxy (left-right axis malformation). Inversion Inv(11)(q13.5;q25).

PTM

Phosphorylated at Ser-498 by MTOR under basal conditions; increases the interaction with RUBCN implicated in inhibitory effect of RUBCN on PI3KC3 and decreases interaction with RAB7,A and VPS16 and VPS39 (indicative for a class C Vps complex, possibly the HOPS complex) (PubMed:25533187).