Protein: Autophagy-related protein 8 (Autophagy-related ubiquitin-like modifier ATG8) (Cytoplasm to vacuole targeting protein 5) (P38182)
Organism: Saccharomyces cerevisiae (strain ATCC 204508 / S288c) (Baker's yeast)
Function: Ubiquitin-like modifier involved in cytoplasm to vacuole transport (Cvt) vesicles and autophagosomes formation. With ATG4, mediates the delivery of the vesicles and autophagosomes to the vacuole via the microtubule cytoskeleton. Required for selective autophagic degradation of the nucleus (nucleophagy) as well as for mitophagy which contributes to regulate mitochondrial quantity and quality by eliminating the mitochondria to a basal level to fulfill cellular energy requirements and preventing excess ROS production. Participates also in membrane fusion events that take place in the early secretory pathway. Also involved in endoplasmic reticulum-specific autophagic process and is essential for the survival of cells subjected to severe ER stress. The ATG8-PE conjugate mediates tethering between adjacent membranes and stimulates membrane hemifusion, leading to expansion of the autophagosomal membrane during autophagy. Moreover not only conjugation, but also subsequent ATG8-PE deconjugation is an important step required to facilitate multiple events during macroautophagy, and especially for efficient autophagosome biogenesis, the assembly of ATG9-containing tubulovesicular clusters into phagophores/autophagosomes, and for the disassembly of PAS-associated ATG components. Also plays a role in regulation of filamentous growth.
Subcellular location: Cytoplasmic vesicle, cvt vesicle membrane; Lipid-anchor {ECO:0000269|PubMed:11100732}. Cytoplasmic vesicle, autophagosome membrane {ECO:0000269|PubMed:11149920, ECO:0000269|PubMed:11689437, ECO:0000269|PubMed:15659643, ECO:0000269|PubMed:16680092, ECO:0000269|PubMed:19398890}; Lipid-anchor {ECO:0000269|PubMed:11100732}. Vacuole membrane {ECO:0000269|PubMed:23549786, ECO:0000269|PubMed:34088313}; Peripheral membrane protein {ECO:0000269|PubMed:34088313}. Mitochondrion membrane {ECO:0000269|PubMed:30510114}; Peripheral membrane protein {ECO:0000269|PubMed:30510114}. Note=Membrane-associated through a lipid anchor. This association needs the 2 ubiquitin-like systems required for cytoplasm to vacuole transport and autophagy. ATG18 and ATG21 facilitate the recruitment of ATG8-PE to the site of autophagosome formation and protect it from premature cleavage by ATG4. Localizes to both the isolation membrane (IM) and the vacuole-isolation membrane contact site (VICS) during IM expansion. The IM is a membrane sac generated from the pre-autophagosomal structure that ultimately expands to become a mature autophagosome. Upon starvation, is also recruited to into unique membrane structures near SEC13-containing ER exit sites which lack components of the Golgi apparatus and the endosomes, and which were called a compartments for unconventional protein secretion (CUPS). Associates with mitochondria following nitrogen starvation in a respiratory carbon source (PubMed:30510114). {ECO:0000269|PubMed:30510114}.
Interaction partners:
- Autophagy-related protein 32
- Putative lipase ATG15
- Ubiquitin-like modifier-activating enzyme ATG7
- Autophagy-related protein 3
- Serine/threonine-protein kinase ATG1
- Ubiquitin-like protein ATG12
- Cysteine protease ATG4
- Autophagy protein 5
- Autophagy protein 16
- Autophagy-related protein 19
Sequence:
MKSTFKSEYPFEKRKAESERIADRFKNRIPVICEKAEKSDIPEIDKRKYLVPADLTVGQFVYVIRKRIMLPPEKAIFIFVNDTLPPTAALMSAIYQEHKDKDGFLYVTYSGENTFGR