ATG15/YCR068W Summary Help

Standard Name ATG15 1
Systematic Name YCR068W
Alias AUT5 2 , CVT17 3
Feature Type ORF, Verified
Description Lipase required for intravacuolar lysis of autophagic and Cvt bodies; targeted to intravacuolar vesicles during autophagy via the multivesicular body (MVB) pathway (2, 4 and see Summary Paragraph)
Name Description AuTophaGy related 1
Chromosomal Location
ChrIII:237214 to 238776 | ORF Map | GBrowse
Gbrowse
Gene Ontology Annotations All ATG15 GO evidence and references
  View Computational GO annotations for ATG15
Molecular Function
Manually curated
Biological Process
Manually curated
Cellular Component
Manually curated
Regulators 5 genes
Resources
Classical genetics
null
overexpression
reduction of function
Large-scale survey
null
overexpression
Resources
57 total interaction(s) for 57 unique genes/features.
Physical Interactions
  • Affinity Capture-RNA: 1
  • PCA: 2
  • Two-hybrid: 3

Genetic Interactions
  • Negative Genetic: 27
  • Positive Genetic: 16
  • Synthetic Growth Defect: 6
  • Synthetic Lethality: 1
  • Synthetic Rescue: 1

Resources
Expression Summary
histogram
Resources
Length (a.a.) 520
Molecular Weight (Da) 58,435
Isoelectric Point (pI) 5.33
Localization
Phosphorylation PhosphoGRID | PhosphoPep Database
Structure
Homologs
sequence information
ChrIII:237214 to 238776 | ORF Map | GBrowse
SGD ORF map
Last Update Coordinates: 2011-02-03 | Sequence: 2000-09-13
Subfeature details
Relative
Coordinates
Chromosomal
Coordinates
Most Recent Updates
Coordinates Sequence
CDS 1..1563 237214..238776 2011-02-03 2000-09-13
Retrieve sequences
Analyze Sequence
S288C only
S288C vs. other species
S288C vs. other strains
Resources
External Links All Associated Seq | E.C. | Entrez Gene | Entrez RefSeq Protein | MIPS | Search all NCBI (Entrez) | UniProtKB
Primary SGDIDS000000664
SUMMARY PARAGRAPH for ATG15

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 5). 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 (6, 7, reviewed in 8). Approximately 30 autophagy-related (Atg) proteins have been identified in S. cerevisiae, 17 of which are essential for formation of the autophagosome (reviewed in 9). 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 (10, 11).

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 (12, 13). 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 (14 and reviewed in 9).

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 (10, 11). 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 15). The Cvt pathway has not been observed outside of yeast, and enzymes specifically involved in this pathway are not well conserved in other organisms (16 and references therein).

about ATG15

ATG15 encodes a transmembrane protein that is required for one of the final stages of autophagy, the degradation of the autophagic vesicle in the vacuole (10, and reviewed in 17). Atg15p is a glycosylated protein containing a functional domain that is conserved among lipases and esterases (3). Atg15p is transported from the ER to the vacuole via the multivesicular body (MVB) pathway and is eventually degraded by vacuolar proteinase A (Pep4p) (2).

atg15 mutants fail to degrade autophagic, Cvt, and intravacuolar MVB vesicles, show a decrease in their total protein turnover rate, and are defective in sporulation (10, 4, 2, 18). ATG15 homologs have been identified in all yeast species and filamentous fungi studied to date, but no ATG15 ortholog has yet been identified in higher eukaryotes (16).

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 (1 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 (1). 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 (16, 19).

Last updated: 2008-02-08 Contact SGD

References cited on this page View Complete Literature Guide for ATG15
1) Klionsky DJ, et al.  (2003) A unified nomenclature for yeast autophagy-related genes. Dev Cell 5(4):539-45
2) Epple UD, et al.  (2001) Aut5/Cvt17p, a putative lipase essential for disintegration of autophagic bodies inside the vacuole. J Bacteriol 183(20):5942-55
3) Teter SA, et al.  (2001) Degradation of lipid vesicles in the yeast vacuole requires function of Cvt17, a putative lipase. J Biol Chem 276(3):2083-7
4) Epple UD, et al.  (2003) Intravacuolar membrane lysis in Saccharomyces cerevisiae. Does vacuolar targeting of Cvt17/Aut5p affect its function? J Biol Chem 278(10):7810-21
5) 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
6) 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
7) Matsuura A, et al.  (1997) Apg1p, a novel protein kinase required for the autophagic process in Saccharomyces cerevisiae. Gene 192(2):245-50
8) Yorimitsu T and Klionsky DJ  (2007) Endoplasmic reticulum stress: a new pathway to induce autophagy. Autophagy 3(2):160-2
9) Suzuki K and Ohsumi Y  (2007) Molecular machinery of autophagosome formation in yeast, Saccharomyces cerevisiae. FEBS Lett 581(11):2156-61
10) 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
11) 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
12) 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
13) Noda T and Ohsumi Y  (1998) Tor, a phosphatidylinositol kinase homologue, controls autophagy in yeast. J Biol Chem 273(7):3963-6
14) 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
15) 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
16) 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
17) Yorimitsu T and Klionsky DJ  (2005) Autophagy: molecular machinery for self-eating. Cell Death Differ 12 Suppl 2():1542-52
18) Enyenihi AH and Saunders WS  (2003) Large-scale functional genomic analysis of sporulation and meiosis in Saccharomyces cerevisiae. Genetics 163(1):47-54
19) Farre JC, et al.  (2008) PpAtg30 tags peroxisomes for turnover by selective autophagy. Dev Cell 14(3):365-76