ATG1/YGL180W Summary Help

Standard Name ATG1 1
Systematic Name YGL180W
Alias AUT3 2 , CVT10 3 , APG1 4
Feature Type ORF, Verified
Description Protein serine/threonine kinase; required for vesicle formation in autophagy and the cytoplasm-to-vacuole targeting (Cvt) pathway; structurally required for phagophore assembly site formation; during autophagy forms a complex with Atg13p and Atg17p; essential for cell cycle progression from G2/M to G1 under nitrogen starvation (5, 6, 7, 8, 9, 10 and see Summary Paragraph)
Name Description AuTophaGy related 1
Chromosomal Location
ChrVII:160065 to 162758 | ORF Map | GBrowse
Gbrowse
Gene Ontology Annotations All ATG1 GO evidence and references
  View Computational GO annotations for ATG1
Molecular Function
Manually curated
High-throughput
Biological Process
Manually curated
High-throughput
Cellular Component
Manually curated
Regulators 4 genes
Resources
Classical genetics
conditional
null
overexpression
reduction of function
Large-scale survey
null
overexpression
Resources
536 total interaction(s) for 373 unique genes/features.
Physical Interactions
  • Affinity Capture-MS: 9
  • Affinity Capture-RNA: 1
  • Affinity Capture-Western: 31
  • Biochemical Activity: 194
  • Co-fractionation: 1
  • Co-purification: 2
  • Reconstituted Complex: 2
  • Two-hybrid: 29

Genetic Interactions
  • Dosage Growth Defect: 26
  • Dosage Rescue: 4
  • Negative Genetic: 166
  • Phenotypic Enhancement: 14
  • Phenotypic Suppression: 7
  • Positive Genetic: 47
  • Synthetic Growth Defect: 2
  • Synthetic Lethality: 1

Resources
Expression Summary
histogram
Resources
Length (a.a.) 897
Molecular Weight (Da) 101,716
Isoelectric Point (pI) 6.61
Localization
Phosphorylation PhosphoGRID | PhosphoPep Database
Structure
Homologs
sequence information
ChrVII:160065 to 162758 | 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..2694 160065..162758 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 | E.C. | Entrez Gene | Entrez RefSeq Protein | MIPS | Search all NCBI (Entrez) | UniProtKB
Primary SGDIDS000003148
SUMMARY PARAGRAPH for ATG1

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 11). 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 (12, 6, 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 (3, 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 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 (3, 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 ATG1

ATG1 encodes a cytosolic protein kinase required for vesicle formation during autophagy and the Cvt pathway (5, 6, 7). Atg1p kinase activity is required for initiation of the Cvt pathway as well as for proper localization and cycling of autophagy proteins such as Atg23p (7, 21). Atg1p also has a role in autophagy unrelated to its kinase activity; it is thought that Atg1p is a structural protein required for efficient PAS organization and assembly (7, 9).

Atg1p kinase activity is stimulated by interaction with Atg13p and Atg17p, and formation of this complex is specific for the role of Atg1p in autophagy initiation (8). Atg1p also interacts with the Cvt pathway-specific protein Atg11p (22). Complementation experiments and the presence of PKA phosphorylation sites on Atg1p suggest that regulation of autophagy by the kinases Snf1p, Pho85p, and PKA may occur via regulation of Atg1p (23, 16).

atg1 mutants are defective in autophagy, Cvt transport, sporulation, and survival under starvation conditions (5, 24). Overexpression of ATG1 inhibits filamentous growth (25). ATG1 is highly conserved, and homologs have been identified in organisms such as soil amoeba (atg1), worms (UNC-51), Drosophila (ATG1), and human (ULK1) (26, 6, 27, 28).

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 (20, 29).

Last updated: 2008-02-08 Contact SGD

References cited on this page View Complete Literature Guide for ATG1
1) Klionsky DJ, et al.  (2003) A unified nomenclature for yeast autophagy-related genes. Dev Cell 5(4):539-45
2) Thumm M, et al.  (1994) Isolation of autophagocytosis mutants of Saccharomyces cerevisiae. FEBS Lett 349(2):275-80
3) 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
4) Tsukada M and Ohsumi Y  (1993) Isolation and characterization of autophagy-defective mutants of Saccharomyces cerevisiae. FEBS Lett 333(1-2):169-74
5) Straub M, et al.  (1997) AUT3, a serine/threonine kinase gene, is essential for autophagocytosis in Saccharomyces cerevisiae. J Bacteriol 179(12):3875-83
6) Matsuura A, et al.  (1997) Apg1p, a novel protein kinase required for the autophagic process in Saccharomyces cerevisiae. Gene 192(2):245-50
7) Abeliovich H, et al.  (2003) Chemical genetic analysis of Apg1 reveals a non-kinase role in the induction of autophagy. Mol Biol Cell 14(2):477-90
8) Kabeya Y, et al.  (2005) Atg17 functions in cooperation with Atg1 and Atg13 in yeast autophagy. Mol Biol Cell 16(5):2544-53
9) Cheong H, et al.  (2008) The Atg1 Kinase Complex Is Involved in the Regulation of Protein Recruitment to Initiate Sequestering Vesicle Formation for Nonspecific Autophagy in Saccharomyces cerevisiae. Mol Biol Cell 19(2):668-81
10) Matsui A, et al.  (2013) The role of autophagy in genome stability through suppression of abnormal mitosis under starvation. PLoS Genet 9(1):e1003245
11) 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
12) 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
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) 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) 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
22) Kamada Y, et al.  (2000) Tor-mediated induction of autophagy via an Apg1 protein kinase complex. J Cell Biol 150(6):1507-13
23) Wang Z, et al.  (2001) Antagonistic controls of autophagy and glycogen accumulation by Snf1p, the yeast homolog of AMP-activated protein kinase, and the cyclin-dependent kinase Pho85p. Mol Cell Biol 21(17):5742-52
24) Enyenihi AH and Saunders WS  (2003) Large-scale functional genomic analysis of sporulation and meiosis in Saccharomyces cerevisiae. Genetics 163(1):47-54
25) Ma J, et al.  (2007) Overexpression of autophagy-related genes inhibits yeast filamentous growth. Autophagy 3(6):604-9
26) Otto GP, et al.  (2003) Macroautophagy is required for multicellular development of the social amoeba Dictyostelium discoideum. J Biol Chem 278(20):17636-45
27) Scott RC, et al.  (2007) Direct induction of autophagy by Atg1 inhibits cell growth and induces apoptotic cell death. Curr Biol 17(1):1-11
28) Kuroyanagi H, et al.  (1998) Human ULK1, a novel serine/threonine kinase related to UNC-51 kinase of Caenorhabditis elegans: cDNA cloning, expression, and chromosomal assignment. Genomics 51(1):76-85
29) Farre JC, et al.  (2008) PpAtg30 tags peroxisomes for turnover by selective autophagy. Dev Cell 14(3):365-76