3gre

Structural highlights

Function

VPS15_YEAST Serine/threonine-protein kinase required for cytoplasm to vacuole transport (Cvt) and autophagy as a part of the autophagy-specific VPS34 PI3-kinase complex I. This complex is essential to recruit the ATG8-phosphatidylinositol conjugate and the ATG12-ATG5 conjugate to the pre-autophagosomal structure. Is also involved in endosome-to-Golgi retrograde transport as part of the VPS34 PI3-kinase complex II. This second complex is required for the endosome-to-Golgi retrieval of PEP1 and KEX2, and the recruitment of VPS5 and VPS7, two components of the retromer complex, to endosomal membranes (probably through the synthesis of a specific pool of phosphatidylinositol 3-phosphate recruiting the retromer to the endosomes). By regulating VPS34 kinase activity, VPS15 appears to be essential for the efficient delivery of soluble hydrolases to the yeast vacuole.^{[1] [2] [3] [4] [5] [6] [7] [8] [9]}

Evolutionary Conservation

Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf.

See Also

• Serine/threonine protein kinase 3D structures
• Vacuolar protein sorting-associated protein 3D structures

References

1. ↑ Herman PK, Stack JH, DeModena JA, Emr SD. A novel protein kinase homolog essential for protein sorting to the yeast lysosome-like vacuole. Cell. 1991 Jan 25;64(2):425-37. PMID:1988155
2. ↑ Robinson JS, Klionsky DJ, Banta LM, Emr SD. Protein sorting in Saccharomyces cerevisiae: isolation of mutants defective in the delivery and processing of multiple vacuolar hydrolases. Mol Cell Biol. 1988 Nov;8(11):4936-48. PMID:3062374
3. ↑ Herman PK, Stack JH, Emr SD. A genetic and structural analysis of the yeast Vps15 protein kinase: evidence for a direct role of Vps15p in vacuolar protein delivery. EMBO J. 1991 Dec;10(13):4049-60. PMID:1756716
4. ↑ Stack JH, Herman PK, Schu PV, Emr SD. A membrane-associated complex containing the Vps15 protein kinase and the Vps34 PI 3-kinase is essential for protein sorting to the yeast lysosome-like vacuole. EMBO J. 1993 May;12(5):2195-204. PMID:8387919
5. ↑ Vida TA, Huyer G, Emr SD. Yeast vacuolar proenzymes are sorted in the late Golgi complex and transported to the vacuole via a prevacuolar endosome-like compartment. J Cell Biol. 1993 Jun;121(6):1245-56. PMID:8509446
6. ↑ Stack JH, Emr SD. Vps34p required for yeast vacuolar protein sorting is a multiple specificity kinase that exhibits both protein kinase and phosphatidylinositol-specific PI 3-kinase activities. J Biol Chem. 1994 Dec 16;269(50):31552-62. PMID:7989323
7. ↑ Nothwehr SF, Bryant NJ, Stevens TH. The newly identified yeast GRD genes are required for retention of late-Golgi membrane proteins. Mol Cell Biol. 1996 Jun;16(6):2700-7. PMID:8649377
8. ↑ Kihara A, Noda T, Ishihara N, Ohsumi Y. Two distinct Vps34 phosphatidylinositol 3-kinase complexes function in autophagy and carboxypeptidase Y sorting in Saccharomyces cerevisiae. J Cell Biol. 2001 Feb 5;152(3):519-30. PMID:11157979
9. ↑ Burda P, Padilla SM, Sarkar S, Emr SD. Retromer function in endosome-to-Golgi retrograde transport is regulated by the yeast Vps34 PtdIns 3-kinase. J Cell Sci. 2002 Oct 15;115(Pt 20):3889-900. PMID:12244127