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 (PtdIns(3)P) (  ). During autophagy acts as a 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 ( , ). 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 ( ). 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 (, ). Enhances class C Vps complex (possibly HOPS complex) association with a SNARE complex and promotes fusogenic SNARE complex formation during late endocytic membrane fusion . 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 .
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) . Required for centrosome stability and proper chromosome segregation .
Subcellular locations: 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 . Recruited to autophagosome following interaction with RUBCNL/PACER .
Highly expressed in brain, lung, kidney and liver.