InterPro domain: IPR018791

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 [ 1 ].

Barkor positively regulates autophagy through its interaction with Beclin-1, with decreased levels of autophagosome formation observed when Barkor expression is eliminated [ 2 ]. UVRAG is also a Beclin1 binding protein that positively stimulate starvation-induced autophagy [ 3 ]. 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 [ 4 ]. In mammals, complex II is also involved in autophagy [ 5 ]. 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 [ 6 ].

1. Apg14p and Apg6/Vps30p form a protein complex essential for autophagy in the yeast, Saccharomyces cerevisiae. J. Biol. Chem. 273, 22284-91
2. Identification of Barkor as a mammalian autophagy-specific factor for Beclin 1 and class III phosphatidylinositol 3-kinase. Proc. Natl. Acad. Sci. U.S.A. 105, 19211-6
3. Autophagic and tumour suppressor activity of a novel Beclin1-binding protein UVRAG. Nat. Cell Biol. 8, 688-99
4. Two distinct Vps34 phosphatidylinositol 3-kinase complexes function in autophagy and carboxypeptidase Y sorting in Saccharomyces cerevisiae. J. Cell Biol. 152, 519-30
5. A phosphatidylinositol 3-kinase class III sub-complex containing VPS15, VPS34, Beclin 1, UVRAG and BIF-1 regulates cytokinesis and degradative endocytic traffic. Exp. Cell Res. 316, 3368-78
6. Beclin 1 forms two distinct phosphatidylinositol 3-kinase complexes with mammalian Atg14 and UVRAG. Mol. Biol. Cell 19, 5360-72