W0THY6 · ATG8_KLUMD
- ProteinAutophagy-related protein 8
- GeneATG8
- StatusUniProtKB reviewed (Swiss-Prot)
- Amino acids124 (go to sequence)
- Protein existenceEvidence at protein level
- Annotation score4/5
Function
function
Ubiquitin-like modifier involved in cytoplasm to vacuole transport (Cvt) vesicles and autophagosome formation (PubMed:26442587).
With ATG4, mediates the delivery of the vesicles and autophagosomes to the vacuole via the microtubule cytoskeleton (By similarity).
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 (By similarity).
Participates also in membrane fusion events that take place in the early secretory pathway (By similarity).
Also involved in endoplasmic reticulum-specific autophagic process and is essential for the survival of cells subjected to severe ER stress (By similarity).
The ATG8-PE conjugate mediates tethering between adjacent membranes and stimulates membrane hemifusion, leading to expansion of the autophagosomal membrane during autophagy (By similarity).
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 (By similarity).
With ATG4, mediates the delivery of the vesicles and autophagosomes to the vacuole via the microtubule cytoskeleton (By similarity).
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 (By similarity).
Participates also in membrane fusion events that take place in the early secretory pathway (By similarity).
Also involved in endoplasmic reticulum-specific autophagic process and is essential for the survival of cells subjected to severe ER stress (By similarity).
The ATG8-PE conjugate mediates tethering between adjacent membranes and stimulates membrane hemifusion, leading to expansion of the autophagosomal membrane during autophagy (By similarity).
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 (By similarity).
Miscellaneous
Kluyveromyces marxianus proteins are shorter in length and have a more ordered secondary structure than their S.cerevisiae counterparts, which might contribute to the superior thermotolerance and solubility (PubMed:26442587).
K.marxianus could be therefore useful as a new model organism for further elucidation of the molecular details of autophagy (PubMed:26442587).
K.marxianus could be therefore useful as a new model organism for further elucidation of the molecular details of autophagy (PubMed:26442587).
Features
Showing features for site.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Site | 116-117 | Cleavage; by ATG4 | ||||
Sequence: GG |
GO annotations
Aspect | Term | |
---|---|---|
Cellular Component | autophagosome membrane | |
Cellular Component | Cvt vesicle membrane | |
Cellular Component | cytosol | |
Cellular Component | fungal-type vacuole membrane | |
Molecular Function | phosphatidylethanolamine binding | |
Biological Process | cellular response to nitrogen starvation | |
Biological Process | macroautophagy | |
Biological Process | protein transport |
Keywords
- Biological process
Names & Taxonomy
Protein names
- Recommended nameAutophagy-related protein 8
- Alternative names
Gene names
Organism names
- Strain
- Taxonomic lineageEukaryota > Fungi > Dikarya > Ascomycota > Saccharomycotina > Saccharomycetes > Saccharomycetales > Saccharomycetaceae > Kluyveromyces
Accessions
- Primary accessionW0THY6
Proteomes
Organism-specific databases
Subcellular Location
UniProt Annotation
GO Annotation
Cytoplasmic vesicle, cvt vesicle membrane ; Lipid-anchor
Cytoplasmic vesicle, autophagosome membrane ; Lipid-anchor
Vacuole membrane ; Lipid-anchor
Note: Membrane-associated through a lipid anchor (By similarity).
This association needs the 2 ubiquitin-like systems required for cytoplasm to vacuole transport and autophagy (By similarity).
Localizes to both the isolation membrane (IM) and the vacuole-isolation membrane contact site (VICS) during IM expansion (By similarity).
The IM is a membrane sac generated from the pre-autophagosomal structure that ultimately expands to become a mature autophagosome (By similarity).
Accumulates atperivacuolar sites under high temperature conditions (PubMed:26442587).
This association needs the 2 ubiquitin-like systems required for cytoplasm to vacuole transport and autophagy (By similarity).
Localizes to both the isolation membrane (IM) and the vacuole-isolation membrane contact site (VICS) during IM expansion (By similarity).
The IM is a membrane sac generated from the pre-autophagosomal structure that ultimately expands to become a mature autophagosome (By similarity).
Accumulates atperivacuolar sites under high temperature conditions (PubMed:26442587).
Keywords
- Cellular component
Phenotypes & Variants
Disruption phenotype
Blocks autophagic activity by impairing the formation of autophagic bodies (PubMed:26442587).
Features
Showing features for mutagenesis.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Mutagenesis | 116 | In Atg8FA; prevents conjugation with phosphatidylethanolamine (PE) and impairs the correct localization to autophagic membranes. | ||||
Sequence: G → A | ||||||
Mutagenesis | 117-124 | In Atg8FG; bypasses the requirement for cleavage by ATG4 to be localized to autophagic membranes. | ||||
Sequence: Missing |
PTM/Processing
Features
Showing features for chain, lipidation, propeptide.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Chain | PRO_0000443891 | 1-124 | Autophagy-related protein 8 | |||
Sequence: MKSAFKSEFPFEKRKAESERIVQKFHNRIPVICERGGKSDIPDIDKRKYLVPGDLTVGQFVYVIRKRIKLPAEKAIFIFVNDTLPPTAALMSSIYQHHKDKDGFLYVSYSSENTFGGAGPLLEK | ||||||
Lipidation | 116 | Phosphatidylethanolamine amidated glycine | ||||
Sequence: G | ||||||
Propeptide | PRO_0000443892 | 117-124 | Removed in mature form | |||
Sequence: GAGPLLEK |
Post-translational modification
The C-terminal 8 residues of ATG8 are removed by ATG4 to expose Gly-116 at the C-terminus (By similarity).
This Gly-116 forms then a thioester bond with the 'Cys-550' of ATG7 (E1-like activating enzyme) before being transferred to the 'Cys-244' of ATG3 (the specific E2 conjugating enzyme), in order to be finally amidated with phosphatidylethanolamine (By similarity).
This lipid modification anchors ATG8 to membranes and can be reversed by ATG4, releasing soluble ATG8 (By similarity).
This Gly-116 forms then a thioester bond with the 'Cys-550' of ATG7 (E1-like activating enzyme) before being transferred to the 'Cys-244' of ATG3 (the specific E2 conjugating enzyme), in order to be finally amidated with phosphatidylethanolamine (By similarity).
This lipid modification anchors ATG8 to membranes and can be reversed by ATG4, releasing soluble ATG8 (By similarity).
Keywords
- PTM
Interaction
Subunit
Conjugation to phosphatidylethanolamine (PE) leads to homodimerization (By similarity).
Interacts with ATG1, ATG3, ATG4, ATG7 and ATG12 (By similarity).
Interacts with ATG1, ATG3, ATG4, ATG7 and ATG12 (By similarity).
Structure
Sequence
- Sequence statusComplete
- Sequence processingThe displayed sequence is further processed into a mature form.
- Length124
- Mass (Da)14,137
- Last updated2014-03-19 v1
- Checksum2E5BAF8E7A9464A3