VPS30/YPL120W Summary Help

Standard Name VPS30 1, 2
Systematic Name YPL120W
Alias APG6 3 , VPT30 1 , ATG6 4
Feature Type ORF, Verified
Description Subunit of phosphatidylinositol (PtdIns) 3-kinase complexes I and II; Complex I is essential in autophagy and Complex II is required for vacuolar protein sorting; required for overflow degradation of misfolded proteins when ERAD is saturated; C-terminus has a novel globular fold that is essential for autophagy through the targeting of the PI3-kinase complex I to the pre-autophagosomal structure; ortholog of the higher eukaryotic gene Beclin 1 (3, 5, 6, 7, 8 and see Summary Paragraph)
Name Description Vacuolar Protein Sorting 1, 2
Chromosomal Location
ChrXVI:322071 to 323744 | ORF Map | GBrowse
Gbrowse
Gene Ontology Annotations All VPS30 GO evidence and references
  View Computational GO annotations for VPS30
Molecular Function
Manually curated
Biological Process
Manually curated
Cellular Component
Manually curated
High-throughput
Regulators 4 genes
Resources
Classical genetics
null
reduction of function
Large-scale survey
null
overexpression
Resources
286 total interaction(s) for 189 unique genes/features.
Physical Interactions
  • Affinity Capture-MS: 13
  • Affinity Capture-RNA: 1
  • Affinity Capture-Western: 7
  • Reconstituted Complex: 1
  • Two-hybrid: 2

Genetic Interactions
  • Dosage Lethality: 1
  • Negative Genetic: 194
  • Phenotypic Enhancement: 6
  • Phenotypic Suppression: 5
  • Positive Genetic: 39
  • Synthetic Growth Defect: 11
  • Synthetic Lethality: 2
  • Synthetic Rescue: 4

Resources
Expression Summary
histogram
Resources
Length (a.a.) 557
Molecular Weight (Da) 63,260
Isoelectric Point (pI) 4.79
Localization
Phosphorylation PhosphoGRID | PhosphoPep Database
Structure
Homologs
sequence information
ChrXVI:322071 to 323744 | ORF Map | GBrowse
SGD ORF map
Last Update Coordinates: 2011-02-03 | Sequence: 1996-07-31
Subfeature details
Relative
Coordinates
Chromosomal
Coordinates
Most Recent Updates
Coordinates Sequence
CDS 1..1674 322071..323744 2011-02-03 1996-07-31
Retrieve sequences
Analyze Sequence
S288C only
S288C vs. other species
S288C vs. other strains
Resources
External Links All Associated Seq | Entrez Gene | Entrez RefSeq Protein | MIPS | Search all NCBI (Entrez) | UniProtKB
Primary SGDIDS000006041
SUMMARY PARAGRAPH for VPS30

about autophagy...

Autophagy is a highly conserved eukaryotic pathway for sequestering and transporting bulk cytoplasm, including proteins and organelle material, to the lysosome for degradation (reviewed in 9). Upon starvation for nutrients such as carbon, nitrogen, sulfur, and various amino acids, or upon endoplasmic reticulum stress, cells initiate formation of a double-membrane vesicle, termed an autophagosome, that mediates this process (10, 11, reviewed in 12). Approximately 30 autophagy-related (Atg) proteins have been identified in S. cerevisiae, 17 of which are essential for formation of the autophagosome (reviewed in 13). Null mutations in most of these genes prevent induction of autophagy, and cells do not survive nutrient starvation; however, these mutants are viable in rich medium. Some of the Atg proteins are also involved in a constitutive biosynthetic process termed the cytoplasm-to-vacuole targeting (Cvt) pathway, which uses autophagosomal-like vesicles for selective transport of hydrolases aminopeptidase I (Lap4p) and alpha-mannosidase (Ams1p) to the vacuole (14, 15).

Autophagy proceeds via a multistep pathway (a summary diagram (download pdf) kindly provided by Dan Klionsky). First, nutrient availability is sensed by the TORC1 complex and also cooperatively by protein kinase A and Sch9p (16, 17). Second, signals generated by the sensors are transmitted to the autophagosome-generating machinery comprised of the 17 Atg gene products. These 17 proteins collectively form the pre-autophagosomal structure/phagophore assembly site (PAS). The PAS generates an isolation membrane (IM), which expands and eventually fuses along the edges to complete autophagosome formation. At the vacuole the outer membrane of the autophagosome fuses with the vacuolar membrane and autophagic bodies are released, disintegrated, and their contents degraded for reuse in biosynthesis (18 and reviewed in 13).

about the Cytoplasm-to-vacuole targeting (Cvt) pathway

Cytoplasm-to-vacuole targeting (Cvt) is a constitutive and specific form of autophagy that uses autophagosomal-like vesicles for selective transport of hydrolases aminopeptidase I (Lap4p) and alpha-mannosidase (Ams1p) to the vacuole (14, 15). Unlike autophagy, which is primarily a catabolic process, Cvt is a biosynthetic process. Like autophagosomes, Cvt vesicles form at a structure known as the phagophore assembly site (PAS) (also called the pre-autophagosomal structure). The PAS structure generates an isolation membrane (IM), which expands and eventually fuses along the edges to complete vesicle formation. At the vacuole, the outer membrane of the Cvt vesicle fuses with the vacuolar membrane, the vesicle is degraded, and the cargos are released and processed into their mature forms by vacuolar peptidases (reviewed in 19). The Cvt pathway has not been observed outside of yeast, and enzymes specifically involved in this pathway are not well conserved in other organisms (20 and references therein).

about VPS30

Vps30p is a subunit of two distinct phosphatidylinositol (PtdIns) 3-kinase complexes: Complex I, which is involved in autophagy, and Complex II, which functions in vacuolar protein sorting (6). Both complexes contain Vps30p, the PtdIns 3-kinase Vps34p, and Vps15p, a regulatory kinase that tethers the complexes to membranes and activates Vps34p activity. Additionally, each complex contains one unique subunit which acts as a connector between Vps30p and the rest of the complex: Atg14p in Complex I and Vps38p in Complex II (21 and references therein, and reviewed in 22).

Vps30p localizes to vacuolar membranes, endosomes, and the PAS. Vps30p localization to endosomes is dependent on Vps38p while PAS localization is Atg14p-dependent (21). Vps30p is itself required for proper localization of Atg8p and the Atg5p-Atg12p.Atg16p complex to the PAS (23). Mutations in vps30 lead to lower PtdIns 3-phosphate levels, sensitivity to chemicals that induce the unfolded protein response, and defects in autophagy, vacuolar targeting of carboxypeptidase Y (Prc1p), ER-associated protein degradation (ERAD), and retrograde transport from the endosome to the Golgi (5, 24, 7, 25, 26).

VPS30 is highly conserved, and homologs have been identified in organisms such as soil amoeba (atg6), Arabidopsis (atg6), worm (bec-1), mouse (beclin-1), and human (BECN1) (27 and reviewed in 22). In other organisms, Vps30p orthologs have been shown to be involved in the processes of autophagy, development, life-span regulation, apoptosis, and tumor suppression (reviewed in 22).

about autophagy nomenclature

The initial identification of factors involved in autophagy was carried out by several independent labs, which led to a proliferation of nomenclature for the genes and gene products involved. The differing gene name acronyms from these groups included APG, AUT, CVT, GSA, PAG, PAZ, and PDD (4 and references therein). A concerted effort was made in 2003 by the scientists working in the field to unify the nomenclature for these genes, and "AuTophaGy-related" genes are now denoted by the letters ATG (4). In addition to the ATG gene names that have been assigned to S. cerevisiae proteins and their orthologs, several ATG gene names, including ATG25, ATG28, and ATG30, have been used to designate proteins in other ascomycete yeast species for which there is no identifiable equivalent in S. cerevisiae (20, 28).

Last updated: 2008-02-08 Contact SGD

References cited on this page View Complete Literature Guide for VPS30
1) Robinson JS, et al.  (1988) Protein sorting in Saccharomyces cerevisiae: isolation of mutants defective in the delivery and processing of multiple vacuolar hydrolases. Mol Cell Biol 8(11):4936-48
2) Rothman JH, et al.  (1989) Characterization of genes required for protein sorting and vacuolar function in the yeast Saccharomyces cerevisiae. EMBO J 8(7):2057-65
3) Tsukada M and Ohsumi Y  (1993) Isolation and characterization of autophagy-defective mutants of Saccharomyces cerevisiae. FEBS Lett 333(1-2):169-74
4) Klionsky DJ, et al.  (2003) A unified nomenclature for yeast autophagy-related genes. Dev Cell 5(4):539-45
5) Seaman MN, et al.  (1997) Endosome to Golgi retrieval of the vacuolar protein sorting receptor, Vps10p, requires the function of the VPS29, VPS30, and VPS35 gene products. J Cell Biol 137(1):79-92
6) Kihara A, et al.  (2001) Two distinct Vps34 phosphatidylinositol 3-kinase complexes function in autophagy and carboxypeptidase Y sorting in Saccharomyces cerevisiae. J Cell Biol 152(3):519-30
7) Kruse KB, et al.  (2006) Characterization of an ERAD gene as VPS30/ATG6 reveals two alternative and functionally distinct protein quality control pathways: one for soluble Z variant of human alpha-1 proteinase inhibitor (A1PiZ) and another for aggregates of A1PiZ. Mol Biol Cell 17(1):203-12
8) Furuya N, et al.  (2005) The evolutionarily conserved domain of Beclin 1 is required for Vps34 binding, autophagy and tumor suppressor function. Autophagy 1(1):46-52
9) Budovskaya YV, et al.  (2004) The Ras/cAMP-dependent protein kinase signaling pathway regulates an early step of the autophagy process in Saccharomyces cerevisiae. J Biol Chem 279(20):20663-71
10) Takeshige K, et al.  (1992) Autophagy in yeast demonstrated with proteinase-deficient mutants and conditions for its induction. J Cell Biol 119(2):301-11
11) Matsuura A, et al.  (1997) Apg1p, a novel protein kinase required for the autophagic process in Saccharomyces cerevisiae. Gene 192(2):245-50
12) Yorimitsu T and Klionsky DJ  (2007) Endoplasmic reticulum stress: a new pathway to induce autophagy. Autophagy 3(2):160-2
13) Suzuki K and Ohsumi Y  (2007) Molecular machinery of autophagosome formation in yeast, Saccharomyces cerevisiae. FEBS Lett 581(11):2156-61
14) Harding TM, et al.  (1996) Genetic and phenotypic overlap between autophagy and the cytoplasm to vacuole protein targeting pathway. J Biol Chem 271(30):17621-4
15) Yorimitsu T and Klionsky DJ  (2005) Atg11 links cargo to the vesicle-forming machinery in the cytoplasm to vacuole targeting pathway. Mol Biol Cell 16(4):1593-605
16) Yorimitsu T, et al.  (2007) Protein Kinase A and Sch9 Cooperatively Regulate Induction of Autophagy in Saccharomyces cerevisiae. Mol Biol Cell 18(10):4180-9
17) Noda T and Ohsumi Y  (1998) Tor, a phosphatidylinositol kinase homologue, controls autophagy in yeast. J Biol Chem 273(7):3963-6
18) Suzuki K, et al.  (2001) The pre-autophagosomal structure organized by concerted functions of APG genes is essential for autophagosome formation. EMBO J 20(21):5971-81
19) Kim J and Klionsky DJ  (2000) Autophagy, cytoplasm-to-vacuole targeting pathway, and pexophagy in yeast and mammalian cells. Annu Rev Biochem 69:303-42
20) Meijer WH, et al.  (2007) ATG genes involved in non-selective autophagy are conserved from yeast to man, but the selective Cvt and pexophagy pathways also require organism-specific genes. Autophagy 3(2):106-16
21) Obara K, et al.  (2006) Assortment of phosphatidylinositol 3-kinase complexes--Atg14p directs association of complex I to the pre-autophagosomal structure in Saccharomyces cerevisiae. Mol Biol Cell 17(4):1527-39
22) Cao Y and Klionsky DJ  (2007) Physiological functions of Atg6/Beclin 1: a unique autophagy-related protein. Cell Res 17(10):839-49
23) Suzuki K, et al.  (2007) Hierarchy of Atg proteins in pre-autophagosomal structure organization. Genes Cells 12(2):209-18
24) Kametaka S, et al.  (1998) Apg14p and Apg6/Vps30p form a protein complex essential for autophagy in the yeast, Saccharomyces cerevisiae. J Biol Chem 273(35):22284-91
25) Burda P, et al.  (2002) Retromer function in endosome-to-Golgi retrograde transport is regulated by the yeast Vps34 PtdIns 3-kinase. J Cell Sci 115(Pt 20):3889-900
26) Chen Y, et al.  (2005) Identification of mitogen-activated protein kinase signaling pathways that confer resistance to endoplasmic reticulum stress in Saccharomyces cerevisiae. Mol Cancer Res 3(12):669-77
27) Otto GP, et al.  (2003) Macroautophagy is required for multicellular development of the social amoeba Dictyostelium discoideum. J Biol Chem 278(20):17636-45
28) Farre JC, et al.  (2008) PpAtg30 tags peroxisomes for turnover by selective autophagy. Dev Cell 14(3):365-76