This entry includes Vps38 from budding yeasts. Vps38 is involved in endosome-to-Golgi retrograde transport as part of the VPS34 PI3-kinase complex II [].The class III phosphatidylinositol-3-kinase (PI3K) known as Vps34 regulates intracellular membrane trafficking in endocytic sorting, cytokinesis and autophagy. Vps34 forms complexes with other proteins: Vps15, Vps30 (encoded by VPS30/ATG6 in yeast, equivalent to mammalian Beclin 1, encoded by BECN1) and either Vps38 (UVRAG) or Atg14 (ATG14L). Although the N-terminal domains of Vps30, Vps38 and Atg14 differ, the overall similarity of their domain organizations suggests that these proteins may have evolved from a common ancestor [].
This entry includes Atg14 (autophagy-related protein 14) from budding yeasts, Vps38 from fission yeasts and their homologues, Atg14L/Bakor (beclin-1-associated autophagy-related key regulator) and UVRAG (UV irradiation resistance-associated gene), from animals. Atg14 is a hydrophilic protein with a coiled-coil motif at the N terminus region. Yeast cells with mutant Atg14 are defective not only in autophagy but also in sorting of carboxypeptidase Y (CPY), a vacuolar-soluble hydrolase, to the vacuole [].Barkor positively regulates autophagy through its interaction with Beclin-1, with decreased levels of autophagosome formation observed when Barkor expression is eliminated []. UVRAG is also a Beclin1 binding protein that positively stimulate starvation-induced autophagy []. Autophagy mediates the cellular response to nutrient deprivation, protein aggregation, and pathogen invasion in humans, and malfunction of autophagy has been implicated in multiple human diseases including cancer. Class III phosphatidylinositol 3-kinase (PI3-kinase) regulates multiple membrane trafficking. In yeast, two distinct PI3-kinase complexes are known: complex I (Vps34, Vps15, Vps30/Atg6, and Atg14) is involved in autophagy, andcomplex II (Vps34, Vps15, Vps30/Atg6, and Vps38) functions in the vacuolar protein sorting pathway []. In mammals, complex II is also involved in autophagy []. The mammalian counterparts of Vps34, Vps15, and Vps30/Atg6 are Vps34, p150, and Beclin 1, respectively, and UV irradiation resistance-associated gene (UVRAG) has been identified as identical to yeast Vps38 [].
In yeasts, vacuolar protein sorting-associated protein 30 (Vps30), also known as autophagy-related protein 6 (Atg6), is a common component of two distinct phosphatidylinositol 3-kinase complexes. In complex I, Atg14 links Vps30 to Vps34 lipid kinase and plays a specific role in autophagy, while in complex II, Vps38 links Vps30 to Vps34 and plays an important role in vacuolar protein sorting []. The C-terminal of Vps30 contains a globular fold comprised of three β-sheet-α-helix repeats (also known as beta-alpha repeated, autophagy-specific (BARA) domain) and is required for autophagy through the targeting of complex I to the pre-autophagosomal structure. The N-terminal of Vps30 is required for vacuolar protein sorting []. Beclin, the mammalian homologue of yeast Atg6/Vps30, isa tumour suppressor that coordinately regulates the autophagy and membrane trafficking involved in several physiological and pathological processes [, ].
In yeasts, vacuolar protein sorting-associated protein 30 (Vps30), also known as autophagy-related protein 6 (Atg6), is a common component of two distinct phosphatidylinositol 3-kinase complexes. In complex I, Atg14 links Vps30 to Vps34 lipid kinase and plays a specific role in autophagy, while in complex II, Vps38 links Vps30 to Vps34 and plays an important role in vacuolar protein sorting []. The C-terminal of Vps30 contains a globular fold comprised of three β-sheet-α-helix repeats (also known as beta-alpha repeated, autophagy-specific (BARA) domain) and is required for autophagy through the targeting of complex I to the pre-autophagosomal structure. The N-terminal of Vps30 is required for vacuolar protein sorting []. Beclin, the mammalian homologue of yeast Atg6/Vps30, is a tumour suppressor that coordinately regulates the autophagy and membrane trafficking involved in several physiological and pathological processes [, ].
