ATG9/YDL149W Summary Help

Standard Name ATG9 1
Systematic Name YDL149W
Alias AUT9 2 , CVT7 3 , 4 , APG9 4 , 5 , CVT6 6
Feature Type ORF, Verified
Description Transmembrane protein involved in forming Cvt and autophagic vesicles; cycles between the phagophore assembly site (PAS) and other cytosolic punctate structures, not found in autophagosomes; may be involved in membrane delivery to the PAS (5, 7, 8, 9 and see Summary Paragraph)
Name Description AuTophaGy related 1
Chromosomal Location
ChrIV:184925 to 187918 | ORF Map | GBrowse
Gbrowse
Gene Ontology Annotations All ATG9 GO evidence and references
  View Computational GO annotations for ATG9
Molecular Function
Manually curated
Biological Process
Manually curated
Cellular Component
Manually curated
High-throughput
Regulators 3 genes
Resources
Classical genetics
null
reduction of function
Large-scale survey
null
Resources
106 total interaction(s) for 79 unique genes/features.
Physical Interactions
  • Affinity Capture-MS: 7
  • Affinity Capture-RNA: 1
  • Affinity Capture-Western: 13
  • Biochemical Activity: 5
  • Co-fractionation: 3
  • Co-localization: 5
  • PCA: 1
  • Reconstituted Complex: 1
  • Two-hybrid: 16

Genetic Interactions
  • Negative Genetic: 40
  • Positive Genetic: 13
  • Synthetic Growth Defect: 1

Resources
Expression Summary
histogram
Resources
Length (a.a.) 997
Molecular Weight (Da) 115,402
Isoelectric Point (pI) 5.86
Localization
Phosphorylation PhosphoGRID | PhosphoPep Database
Structure
Homologs
sequence information
ChrIV:184925 to 187918 | 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..2994 184925..187918 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 SGDIDS000002308
SUMMARY PARAGRAPH for ATG9

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 10). 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 (11, 12, reviewed in 13). Approximately 30 autophagy-related (Atg) proteins have been identified in S. cerevisiae, 17 of which are essential for formation of the autophagosome (reviewed in 14). 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 (15, 16).

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 (17, 18). 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 (19 and reviewed in 14).

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 (15, 16). 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 20). The Cvt pathway has not been observed outside of yeast, and enzymes specifically involved in this pathway are not well conserved in other organisms (21 and references therein).

about ATG9

Atg9p is required for both the bulk autophagy and Cvt pathways and is directly involved in formation of the sequestering vesicle (5, 3, 7). Atg9p is an integral membrane protein that localizes to the PAS and to smaller punctate structures throughout the cytoplasm and on the surface of mitochondria (7, 2, 22). Atg9p cycles between these locations by a process that allows it to remain associated with lipid bilayers (22). These findings have led to hypotheses that Atg9p may serve as a membrane carrier, and that mitochondria may be a membrane source, for the formation of the pre-autophagosome (reviewed in 23). Shuttling occurs whether the cells are maintained in conditions in which the Cvt pathway is operative (growing state) or in conditions that promote autophagy (starvation state) (22, 8).

Anterograde transport of Atg9p to the PAS is facilitated by Atg11p, Atg23p, and Atg27p; Atg23p and Atg27p also localize to punctate structures and the PAS and have been shown to form a complex with Atg9p (9). Atg9p is not a component of completed autophagosomes, and retrograde transport from the PAS back to its mitochondrial and cytoplasmic locations is mediated by a general process that requires the Atg1p-Atg13p complex, Atg2p, Atg18p, and phosphatidylinositol-3-phosphate kinase complex I (for both Cvt and bulk autophagy pathways; 8).

Atg9p homologs have been found in other organisms including plants and humans (24, 25). The mammalian homolog, mAtg9, exhibits a different subcellular distribution from S. cerevisiae Atg9p: it localizes to the trans-Golgi network and to late endosomes (26). Starvation conditions that upregulate autophagy cause mAtg9 to redistribute to peripheral, endosomal membranes, which are autophagosomal intermediates (26).

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 (21, 27).

Last updated: 2008-02-08 Contact SGD

References cited on this page View Complete Literature Guide for ATG9
1) Klionsky DJ, et al.  (2003) A unified nomenclature for yeast autophagy-related genes. Dev Cell 5(4):539-45
2) Lang T, et al.  (2000) Autophagy and the cvt pathway both depend on AUT9. J Bacteriol 182(8):2125-33
3) Harding TM, et al.  (1995) Isolation and characterization of yeast mutants in the cytoplasm to vacuole protein targeting pathway. J Cell Biol 131(3):591-602
4) Kim, J. et al.  (1998) CVT7 and APG9 are allelic
5) Tsukada M and Ohsumi Y  (1993) Isolation and characterization of autophagy-defective mutants of Saccharomyces cerevisiae. FEBS Lett 333(1-2):169-74
6) Lynch-Day MA and Klionsky DJ  (2010) The Cvt pathway as a model for selective autophagy. FEBS Lett 584(7):1359-66
7) Noda T, et al.  (2000) Apg9p/Cvt7p is an integral membrane protein required for transport vesicle formation in the Cvt and autophagy pathways. J Cell Biol 148(3):465-80
8) Reggiori F, et al.  (2004) The Atg1-Atg13 complex regulates Atg9 and Atg23 retrieval transport from the pre-autophagosomal structure. Dev Cell 6(1):79-90
9) Legakis JE, et al.  (2007) A cycling protein complex required for selective autophagy. Autophagy 3(5):422-32
10) 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
11) 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
12) Matsuura A, et al.  (1997) Apg1p, a novel protein kinase required for the autophagic process in Saccharomyces cerevisiae. Gene 192(2):245-50
13) Yorimitsu T and Klionsky DJ  (2007) Endoplasmic reticulum stress: a new pathway to induce autophagy. Autophagy 3(2):160-2
14) Suzuki K and Ohsumi Y  (2007) Molecular machinery of autophagosome formation in yeast, Saccharomyces cerevisiae. FEBS Lett 581(11):2156-61
15) 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
16) 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
17) 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
18) Noda T and Ohsumi Y  (1998) Tor, a phosphatidylinositol kinase homologue, controls autophagy in yeast. J Biol Chem 273(7):3963-6
19) 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
20) 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
21) 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
22) Reggiori F, et al.  (2005) Atg9 cycles between mitochondria and the pre-autophagosomal structure in yeasts. Autophagy 1(2):101-9
23) He C and Klionsky DJ  (2007) Atg9 trafficking in autophagy-related pathways. Autophagy 3(3):271-4
24) Hanaoka H, et al.  (2002) Leaf senescence and starvation-induced chlorosis are accelerated by the disruption of an Arabidopsis autophagy gene. Plant Physiol 129(3):1181-93
25) Yamada T, et al.  (2005) Endothelial nitric-oxide synthase antisense (NOS3AS) gene encodes an autophagy-related protein (APG9-like2) highly expressed in trophoblast. J Biol Chem 280(18):18283-90
26) Young AR, et al.  (2006) Starvation and ULK1-dependent cycling of mammalian Atg9 between the TGN and endosomes. J Cell Sci 119(Pt 18):3888-900
27) Farre JC, et al.  (2008) PpAtg30 tags peroxisomes for turnover by selective autophagy. Dev Cell 14(3):365-76