ATG22/YCL038C Summary Help

Standard Name ATG22 1
Systematic Name YCL038C
Alias AUT4 2
Feature Type ORF, Verified
Description Vacuolar integral membrane protein required for efflux of amino acids; required for efflux of amino acids during autophagic body breakdown in the vacuole; null mutation causes a gradual loss of viability during starvation (3, 4, 5 and see Summary Paragraph)
Name Description AuTophaGy related 1
Chromosomal Location
ChrIII:56527 to 54941 | ORF Map | GBrowse
Note: this feature is encoded on the Crick strand.
Gbrowse
Gene Ontology Annotations All ATG22 GO evidence and references
  View Computational GO annotations for ATG22
Molecular Function
Manually curated
Biological Process
Manually curated
Cellular Component
Manually curated
High-throughput
Regulators 2 genes
Resources
Classical genetics
null
reduction of function
Large-scale survey
null
Resources
20 total interaction(s) for 18 unique genes/features.
Physical Interactions
  • Affinity Capture-MS: 2
  • PCA: 2

Genetic Interactions
  • Negative Genetic: 14
  • Positive Genetic: 2

Resources
Expression Summary
histogram
Resources
Length (a.a.) 528
Molecular Weight (Da) 58,843
Isoelectric Point (pI) 8.59
Localization
Phosphorylation PhosphoGRID | PhosphoPep Database
Structure
Homologs
sequence information
ChrIII:56527 to 54941 | ORF Map | GBrowse
Note: this feature is encoded on the Crick strand.
SGD ORF map
Last Update Coordinates: 2000-09-13 | Sequence: 1997-01-28
Subfeature details
Relative
Coordinates
Chromosomal
Coordinates
Most Recent Updates
Coordinates Sequence
CDS 1..1587 56527..54941 2000-09-13 1997-01-28
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) | TCDB | UniProtKB
Primary SGDIDS000000543
SUMMARY PARAGRAPH for ATG22

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 6). 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 (7, 8, reviewed in 9). Approximately 30 autophagy-related (Atg) proteins have been identified in S. cerevisiae, 17 of which are essential for formation of the autophagosome (reviewed in 10). 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 (2, 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 10).

about ATG22

ATG22 encodes a vacuolar integral membrane protein that functions as an amino acid efflux pump for leucine, a function necessary for cell viability during starvation (5). Atg22p efflux function is required at the last stages of autophagy, when autophagic body breakdown products are recycled to the cytosol (reviewed in 15). Atg22p is partially redundant in function with vacuolar efflux proteins Avt3p and Avt4p (5).

Earlier research suggested that the starved atg22 null mutant is defective in breakdown of autophagic bodies that have reached the vacuole (4). More recent evidence shows that breakdown occurs normally but is delayed (5). This delay is likely an indirect effect of the mutant defect in recycling amino acids that accumulate in the vacuole back into the cytosol upon autophagic body breakdown (5, reviewed in 16). Inappropriate accumulation of these amino acids is thought to affect expression of genes encoding proteins involved in autophagic body breakdown, leading to the apparent delay in breakdown (reviewed in 16).

ATG22 expression increases in response to nitrogen starvation (5). Proteins with varying degrees of similarity to Atg22p are found in most yeast species and filamentous fungi but not in higher eukaryotes (15).

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 (15, 17).

Last updated: 2008-02-08 Contact SGD

References cited on this page View Complete Literature Guide for ATG22
1) Klionsky DJ, et al.  (2003) A unified nomenclature for yeast autophagy-related genes. Dev Cell 5(4):539-45
2) 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
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) Suriapranata I, et al.  (2000) The breakdown of autophagic vesicles inside the vacuole depends on Aut4p. J Cell Sci 113 ( Pt 22):4025-33
5) Yang Z, et al.  (2006) Atg22 recycles amino acids to link the degradative and recycling functions of autophagy. Mol Biol Cell 17(12):5094-104
6) 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
7) 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
8) Matsuura A, et al.  (1997) Apg1p, a novel protein kinase required for the autophagic process in Saccharomyces cerevisiae. Gene 192(2):245-50
9) Yorimitsu T and Klionsky DJ  (2007) Endoplasmic reticulum stress: a new pathway to induce autophagy. Autophagy 3(2):160-2
10) Suzuki K and Ohsumi Y  (2007) Molecular machinery of autophagosome formation in yeast, Saccharomyces cerevisiae. FEBS Lett 581(11):2156-61
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) 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
16) Yang Z and Klionsky DJ  (2007) Permeases recycle amino acids resulting from autophagy. Autophagy 3(2):149-50
17) Farre JC, et al.  (2008) PpAtg30 tags peroxisomes for turnover by selective autophagy. Dev Cell 14(3):365-76