RUBCNL
Function
Regulator of autophagy that promotes autophagosome maturation by facilitating the biogenesis of phosphatidylinositol 3-phosphate (PtdIns(3)P) in late steps of autophagy (PubMed:28306502, PubMed:30704899). Acts by antagonizing RUBCN, thereby stimulating phosphatidylinositol 3-kinase activity of the PI3K/PI3KC3 complex (PubMed:28306502). Following anchorage to the autophagosomal SNARE STX17, promotes the recruitment of PI3K/PI3KC3 and HOPS complexes to the autophagosome to regulate the fusion specificity of autophagosomes with late endosomes/lysosomes (PubMed:28306502). Binds phosphoinositides phosphatidylinositol 3-phosphate (PtdIns(3)P), 4-phosphate (PtdIns(4)P) and 5-phosphate (PtdIns(5)P) (PubMed:28306502). In addition to its role in autophagy, acts as a regulator of lipid and glycogen homeostasis (By similarity). May act as a tumor suppressor (Probable).
Post-translational modifications
Phosphorylated by MTOR at Ser-157 under nutrient-rich conditions (PubMed:30704899). Phosphorylation prevents acetylation by KAT5/TIP60 and impairs RUBCNL/PACER function and autophagosome maturation (PubMed:30704899). Under autophagy induction, Phosphorylation by MTOR is repressed, enabling acetylation by KAT5/TIP60 (PubMed:30704899).
Acetylated by KAT5/TIP60 under autophagy induction, promoting autophagosome maturation and lipid metabolism (PubMed:30704899). Acetylation is prevented by phosphorylation by MTOR (PubMed:30704899). Lys-483 and Lys-573 constitute the key sites for tuning function in autophagy (PubMed:30704899).
Tissue Specificity
Expressed weakly in cervical carcinoma cell lines.
Cellular localization
- Cytoplasmic vesicle
- Autophagosome membrane
- Peripheral membrane protein
- Associates with late autophagic structure (PubMed:28306502). Recruitment to autophagosome membrane is promoted by autophagic stimuli (PubMed:28306502).
Alternative names
C13orf18, KIAA0226L, RUBCNL, Protein associated with UVRAG as autophagy enhancer, Pacer, Protein Rubicon-like