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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 (12, 3, reviewed in 17). Approximately 30 autophagy-related (Atg) proteins have been identified in S. cerevisiae, 17 of which are essential for formation of the autophagosome (reviewed in 18). 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. First, nutrient availability is sensed by the TORC1 complex and also cooperatively by protein kinase A and Sch9p (20, 22). 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 (24 and reviewed in 18).

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 (13 and references therein).about ATG1

ATG1 encodes a cytosolic protein kinase required for vesicle formation during autophagy and the Cvt pathway (2, 3, 4). 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 (4, 16). 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 (4, 5).

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 (6). Atg1p also interacts with the Cvt pathway-specific protein Atg11p (19). 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 (21, 20).

atg1 mutants are defective in autophagy, Cvt transport, sporulation, and survival under starvation conditions (2, 23). 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, 3, 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 (13, 14).", "date_edited": "2008-04-25"}, "literature_overview": {"primary_count": 210, "additional_count": 203, "review_count": 230, "go_count": 23, "phenotype_count": 58, "disease_count": 1, "interaction_count": 121, "regulation_count": 24, "ptm_count": 14, "funComplement_count": 0, "htp_count": 31, "total_count": 729}, "disease_overview": {"manual_disease_terms": [{"annotation_type": "manually curated", "qualifiers": [null], "term": {"link": "/disease/DOID:0060081", "display_name": "triple-receptor negative breast cancer"}, "evidence_codes": [{"display_name": "ISS", "link": "http://wiki.geneontology.org/index.php/Inferred_from_Sequence_or_structural_Similarity_(ISS)"}]}], "htp_disease_terms": [], "computational_annotation_count": 0, "date_last_reviewed": "2021-04-16", "paragraph": "Yeast ATG1 is homologous to human ULK1, and has been used to study triple-receptor negative breast cancer"}, "ecnumbers": [{"display_name": "2.7.11.1", "link": "/ecnumber/EC:2.7.11.1"}], "URS_ID": null, "main_strain": "S288C", "regulation_overview": {"regulator_count": 20, "target_count": 121, "paragraph": {"text": "ATG1 transcription is downregulated by Fyv5p and Spt10p in response to nitrogen starvation, and upregulated by Gcn4p and Sfl1p in response to nitrogen starvation; ATG1 transcription is downregulated by Rph1p in response to nutrient levels; Atg1p activity is upregulated by Snf1p in response to glucose starvation, and by Ptc2p and Ptc3p in response to MMS or rapamycin", "date_edited": "2023-07-26", "references": [{"id": 314926, "display_name": "Bernard A, et al. (2015)", "citation": "Bernard A, et al. (2015) A large-scale analysis of autophagy-related gene expression identifies new regulators of autophagy. Autophagy 11(11):2114-2122", "pubmed_id": 26649943, "link": "/reference/S000182499", "year": 2015, "urls": [{"display_name": "DOI full text", "link": "http://dx.doi.org/10.1080/15548627.2015.1099796"}, {"display_name": "PMC full text", "link": "http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4824583/"}, {"display_name": "PubMed", "link": "http://www.ncbi.nlm.nih.gov/pubmed/26649943"}]}, {"id": 2075463, "display_name": "Memisoglu G, et al. (2019)", "citation": "Memisoglu G, et al. (2019) PP2C phosphatases promote autophagy by dephosphorylation of the Atg1 complex. Proc Natl Acad Sci U S A 116(5):1613-1620", "pubmed_id": 30655342, "link": "/reference/S000246386", "year": 2019, "urls": [{"display_name": "DOI full text", "link": "http://dx.doi.org/10.1073/pnas.1817078116"}, {"display_name": "PMC full text", "link": "http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6358665/"}, {"display_name": "PubMed", "link": "http://www.ncbi.nlm.nih.gov/pubmed/30655342"}]}, {"id": 2387650, "display_name": "Yao W, et al. (2020)", "citation": "Yao W, et al. (2020) Atg11 is required for initiation of glucose starvation-induced autophagy. Autophagy 16(12):2206-2218", "pubmed_id": 31971848, "link": "/reference/S000313692", "year": 2020, "urls": [{"display_name": "DOI full text", "link": "http://dx.doi.org/10.1080/15548627.2020.1719724"}, {"display_name": "PMC full text", "link": "http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7751503/"}, {"display_name": "PubMed", "link": "http://www.ncbi.nlm.nih.gov/pubmed/31971848"}]}]}}, "reference_mapping": {"549294": 1, "646231": 2, "627092": 3, "553508": 4, "493291": 5, "533712": 6, "392153": 7, "2306019": 8, "504318": 9, "594256": 10, "529067": 11, "629040": 12, "509070": 13, "489236": 14, "556282": 15, "545890": 16, "509073": 17, "503381": 18, "640217": 19, "497654": 20, "572756": 21, "584833": 22, "553865": 23, "564292": 24, "497668": 25, "551412": 26, "508479": 27, "614582": 28, "611988": 29, "595080": 30}, "history": [{"category": "Name", "history_type": "LSP", "note": "Name: APG1", "date_created": "2010-02-16", "references": [{"id": 611988, "display_name": "Tsukada M and Ohsumi Y (1993)", "citation": "Tsukada M and Ohsumi Y (1993) Isolation and characterization of autophagy-defective mutants of Saccharomyces cerevisiae. FEBS Lett 333(1-2):169-74", "pubmed_id": 8224160, "link": "/reference/S000051835", "year": 1993, "urls": [{"display_name": "DOI full text", "link": "http://dx.doi.org/10.1016/0014-5793(93)80398-e"}, {"display_name": "PubMed", "link": "http://www.ncbi.nlm.nih.gov/pubmed/8224160"}]}]}, {"category": "Name", "history_type": "LSP", "note": "Name: ATG1", "date_created": "2000-05-19", "references": [{"id": 549294, "display_name": "Klionsky DJ, et al. (2003)", "citation": "Klionsky DJ, et al. (2003) A unified nomenclature for yeast autophagy-related genes. Dev Cell 5(4):539-45", "pubmed_id": 14536056, "link": "/reference/S000074141", "year": 2003, "urls": [{"display_name": "DOI full text", "link": "http://dx.doi.org/10.1016/s1534-5807(03)00296-x"}, {"display_name": "PubMed", "link": "http://www.ncbi.nlm.nih.gov/pubmed/14536056"}]}]}, {"category": "Name", "history_type": "LSP", "note": "Name: AUT3", "date_created": "2010-02-16", "references": [{"id": 595080, "display_name": "Thumm M, et al. (1994)", "citation": "Thumm M, et al. (1994) Isolation of autophagocytosis mutants of Saccharomyces cerevisiae. FEBS Lett 349(2):275-80", "pubmed_id": 8050581, "link": "/reference/S000057585", "year": 1994, "urls": [{"display_name": "DOI full text", "link": "http://dx.doi.org/10.1016/0014-5793(94)00672-5"}, {"display_name": "PubMed", "link": "http://www.ncbi.nlm.nih.gov/pubmed/8050581"}]}]}, {"category": "Name", "history_type": "LSP", "note": "Name: CVT10", "date_created": "2010-02-16", "references": [{"id": 594256, "display_name": "Harding TM, et al. (1996)", "citation": "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", "pubmed_id": 8663607, "link": "/reference/S000057871", "year": 1996, "urls": [{"display_name": "DOI full text", "link": "http://dx.doi.org/10.1074/jbc.271.30.17621"}, {"display_name": "PubMed", "link": "http://www.ncbi.nlm.nih.gov/pubmed/8663607"}]}]}, {"category": "Nomenclature history", "history_type": "LSP", "note": "Nomenclature history: The standard gene name of ORF YGL180W was changed from APG1 to ATG1, as part of the unified autophagy nomenclature agreed upon by the yeast research community. Sept. 10, 2003", "date_created": "2003-09-10", "references": []}, {"category": "Mapping", "history_type": "SEQUENCE", "note": "Mapping: Edition 15: APG1(AUT3) and CVT10 may be allelic", "date_created": "1998-11-10", "references": [{"id": 542517, "display_name": "Cherry JM, et al. (1998)", "citation": "Cherry JM, et al. (1998) \"Genetic and Physical Maps of Saccharomyces cerevisiae (Edition 15)\". Pp. 414-420 in 1998 Yeast Genetics and Molecular Biology Meeting Program and Abstracts. Bethesda, MD: The Genetics Society of America", "pubmed_id": null, "link": "/reference/S000076263", "year": 1998, "urls": []}]}], "complexes": [{"format_name": "CPX-1676", "display_name": "ATG1/ULK1 protein kinase complex"}]}, tabs: {"id": 1268806, "protein_tab": true, "interaction_tab": true, "summary_tab": true, "go_tab": true, "sequence_section": true, "expression_tab": true, "phenotype_tab": true, "literature_tab": true, "wiki_tab": false, "regulation_tab": true, "sequence_tab": true, "history_tab": true, "homology_tab": true, "disease_tab": true} }; ATG1 | SGD

ATG1 / YGL180W Overview


Standard Name
ATG1 1
Systematic Name
YGL180W
SGD ID
SGD:S000003148
Aliases
APG1 29 , CVT10 10 , AUT3 30
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; forms a complex with Atg13p and Atg17p during autophagy; required for re-phosphorylation of Atg13p during termination of autophagy, following prolonged nitrogen starvation; essential for cell cycle progression from G2/M to G1 under nitrogen starvation 2 3 4 5 6 7 8
Name Description
AuTophaGy related 1
Comparative Info
Sequence Details

Sequence

The S. cerevisiae Reference Genome sequence is derived from laboratory strain S288C. Download DNA or protein sequence, view genomic context and coordinates. Click "Sequence Details" to view all sequence information for this locus, including that for other strains.


Summary
ATG1 is located on the left arm of chromosome VII between GTS1 and replication origin ARS707; coding sequence is 2694 nucleotides long with 3 SNPs, 1 of which causes an amino acid polymorphism
Protein Details

Protein

Basic sequence-derived (length, molecular weight, isoelectric point) and experimentally-determined (median abundance, median absolute deviation) protein information. Click "Protein Details" for further information about the protein such as half-life, abundance, domains, domains shared with other proteins, protein sequence retrieval for various strains, physico-chemical properties, protein modification sites, and external identifiers for the protein.


Summary
Atg1p is 897 amino acids long, very long-lived, and low in abundance; has 2 kinase domains; phosphorylated on 46 residues
Length (a.a.)
897
Mol. Weight (Da)
101707.3
Isoelectric Point
6.61
Median Abundance (molecules/cell)
1588 +/- 869
Half-life (hr)
33.5

Alleles

Curated mutant alleles for the specified gene, listed alphabetically. Click on the allele name to open the allele page. Click "SGD search" to view all alleles in search results.


View all ATG1 alleles in SGD search

Gene Ontology Details

Gene Ontology

GO Annotations consist of four mandatory components: a gene product, a term from one of the three Gene Ontology (GO) controlled vocabularies (Molecular Function, Biological Process, and Cellular Component), a reference, and an evidence code. SGD has manually curated and high-throughput GO Annotations, both derived from the literature, as well as computational, or predicted, annotations. Click "Gene Ontology Details" to view all GO information and evidence for this locus as well as biological processes it shares with other genes.


Summary
Protein serine/threonine kinase subunit of the Atg1p signalling complex involved in autophagy and cytoplasm-to-vacuole targeting (CVT) pathways

View computational annotations

Molecular Function

Manually Curated

Cellular Component

Manually Curated

Complex

Macromolecular complex annotations are imported from the Complex Portal. These annotations have been derived from physical molecular interaction evidence extracted from the literature and cross-referenced in the entry, or by curator inference from information on homologs in closely related species or by inference from scientific background.


Phenotype Details

Phenotype

Phenotype annotations for a gene are curated single mutant phenotypes that require an observable (e.g., "cell shape"), a qualifier (e.g., "abnormal"), a mutant type (e.g., null), strain background, and a reference. In addition, annotations are classified as classical genetics or high-throughput (e.g., large scale survey, systematic mutation set). Whenever possible, allele information and additional details are provided. Click "Phenotype Details" to view all phenotype annotations and evidence for this locus as well as phenotypes it shares with other genes.


Summary
Non-essential gene in reference strain S288C; null mutant shows no autophagy, mitophagy or pexophagy, decreased chronological and replicative lifespan, increased sensitivity to nitrogen starvation and is unable to sporulate

Classical Genetics

null
overexpression
reduction of function
conditional
Disease Details

Disease

Disease Annotations consist of three mandatory components: a gene product, a term from the Disease Ontology (DO) controlled vocabulary and an evidence code. SGD provides manually curated DO Annotations derived from the literature. Click "Disease Details" to view all Disease information and evidence for this locus as well as diseases it shares with other genes.


Summary
Yeast ATG1 is homologous to human ULK1, and has been used to study triple-receptor negative breast cancer
Interaction Details

Interaction

Interaction annotations are curated by BioGRID and include physical or genetic interactions observed between at least two genes. An interaction annotation is composed of the interaction type, name of the interactor, assay type (e.g., Two-Hybrid), annotation type (e.g., manual or high-throughput), and a reference, as well as other experimental details. Click "Interaction Details" to view all interaction annotations and evidence for this locus, including an interaction visualization.


Summary
Atg1p interacts physically with proteins involved in protein targeting; ATG1 interacts genetically with genes involved in protein targeting

962 total interactions for 638 unique genes

Physical Interactions

  • Affinity Capture-MS: 49
  • Affinity Capture-RNA: 12
  • Affinity Capture-Western: 60
  • Biochemical Activity: 249
  • Co-fractionation: 1
  • Co-localization: 3
  • Co-purification: 9
  • PCA: 1
  • Protein-RNA: 1
  • Proximity Label-MS: 1
  • Reconstituted Complex: 14
  • Two-hybrid: 32

Genetic Interactions

  • Dosage Growth Defect: 26
  • Dosage Rescue: 4
  • Negative Genetic: 387
  • Phenotypic Enhancement: 18
  • Phenotypic Suppression: 17
  • Positive Genetic: 60
  • Synthetic Growth Defect: 4
  • Synthetic Lethality: 6
  • Synthetic Rescue: 8
Regulation Details

Regulation

The number of putative Regulators (genes that regulate it) and Targets (genes it regulates) for the given locus, based on experimental evidence. This evidence includes data generated through high-throughput techniques. Click "Regulation Details" to view all regulation annotations, shared GO enrichment among regulation Targets, and a regulator/target diagram for the locus.


Summary
ATG1 transcription is downregulated by Fyv5p and Spt10p in response to nitrogen starvation, and upregulated by Gcn4p and Sfl1p in response to nitrogen starvation; ATG1 transcription is downregulated by Rph1p in response to nutrient levels; Atg1p activity is upregulated by Snf1p in response to glucose starvation, and by Ptc2p and Ptc3p in response to MMS or rapamycin
Regulators
20
Targets
121
Expression Details

Expression

Expression data are derived from records contained in the Gene Expression Omnibus (GEO), and are first log2 transformed and normalized. Referenced datasets may contain one or more condition(s), and as a result there may be a greater number of conditions than datasets represented in a single clickable histogram bar. The histogram division at 0.0 separates the down-regulated (green) conditions and datasets from those that are up-regulated (red). Click "Expression Details" to view all expression annotations and details for this locus, including a visualization of genes that share a similar expression pattern.


Summary Paragraph

A summary of the locus, written by SGD Biocurators following a thorough review of the literature. Links to gene names and curated GO terms are included within the Summary Paragraphs.


Last Updated: 2008-04-25

Literature Details

Literature

All manually curated literature for the specified gene, organized into topics according to their relevance to the gene (Primary Literature, Additional Literature, or Review). Click "Literature Details" to view all literature information for this locus, including shared literature between genes.


Primary
210
Additional
203
Reviews
230

Resources