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Protein

Autophagy-related protein 8

Gene

ATG8

Organism
Saccharomyces cerevisiae (strain ATCC 204508 / S288c) (Baker's yeast)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

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. Plays also a role in regulation of filamentous growth.20 Publications

GO - Molecular functioni

  • protein tag Source: SGD

GO - Biological processi

  • autophagosome assembly Source: UniProtKB
  • autophagy Source: UniProtKB
  • cellular protein complex localization Source: SGD
  • cellular response to nitrogen starvation Source: GO_Central
  • CVT pathway Source: SGD
  • ER to Golgi vesicle-mediated transport Source: SGD
  • late nucleophagy Source: SGD
  • membrane fusion Source: SGD
  • mitophagy Source: SGD
  • piecemeal microautophagy of nucleus Source: SGD
  • protein targeting to vacuole involved in autophagy Source: SGD
  • reticulophagy Source: SGD
Complete GO annotation...

Keywords - Biological processi

Autophagy, Protein transport, Transport, Ubl conjugation pathway

Enzyme and pathway databases

BioCyciYEAST:G3O-28969-MONOMER.
ReactomeiR-SCE-1632852. Macroautophagy.

Names & Taxonomyi

Protein namesi
Recommended name:
Autophagy-related protein 8
Alternative name(s):
Autophagy-related ubiquitin-like modifier ATG8
Cytoplasm to vacuole targeting protein 5
Gene namesi
Name:ATG8
Synonyms:APG8, AUT7, CVT5
Ordered Locus Names:YBL078C
ORF Names:YBL0732
OrganismiSaccharomyces cerevisiae (strain ATCC 204508 / S288c) (Baker's yeast)
Taxonomic identifieri559292 [NCBI]
Taxonomic lineageiEukaryotaFungiDikaryaAscomycotaSaccharomycotinaSaccharomycetesSaccharomycetalesSaccharomycetaceaeSaccharomyces
Proteomesi
  • UP000002311 Componenti: Chromosome II

Organism-specific databases

EuPathDBiFungiDB:YBL078C.
SGDiS000000174. ATG8.

Subcellular locationi

  • Cytoplasmic vesiclecvt vesicle membrane; Lipid-anchor
  • Cytoplasmic vesicleautophagosome membrane; Lipid-anchor
  • Vacuole membrane; Lipid-anchor

  • 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).

GO - Cellular componenti

  • autophagosome Source: UniProtKB
  • autophagosome membrane Source: UniProtKB-SubCell
  • Cvt vesicle membrane Source: UniProtKB-SubCell
  • cytoplasm Source: UniProtKB
  • cytosol Source: UniProtKB
  • extrinsic component of membrane Source: SGD
  • fungal-type vacuole membrane Source: SGD
  • pre-autophagosomal structure Source: SGD
Complete GO annotation...

Keywords - Cellular componenti

Cytoplasmic vesicle, Membrane, Vacuole

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Mutagenesisi26 – 261K → P: No effect on autophagic activity. 1 Publication
Mutagenesisi28 – 281R → D: Impairs ATG19-binding and autophagic activity. 2 Publications
Mutagenesisi48 – 481K → E: Impairs autophagic activity. 1 Publication
Mutagenesisi49 – 491Y → A: Impairs ATG19-binding, PE-conjugation, and autophagic activity. 2 Publications
Mutagenesisi50 – 501L → A: Impairs ATG19-binding and autophagic activity. 2 Publications
Mutagenesisi52 – 521P → A: Significantly decreases ATG19-binding and autophagic activity. 1 Publication
Mutagenesisi55 – 551L → A: Impairs autophagic activity. 1 Publication
Mutagenesisi67 – 671R → A: Significantly decreases ATG19-binding and autophagic activity. 1 Publication
Mutagenesisi77 – 771F → A: Impairs interaction with ATG4, cleavage by ATG4, PAS localization, and autophagic activity; when associated with A-79. 1 Publication
Mutagenesisi79 – 791F → A: Impairs interaction with ATG4, cleavage by ATG4, PAS localization, and autophagic activity; when associated with A-77. 1 Publication
Mutagenesisi116 – 1161G → A: No cleaving of the C-terminal R-117 by ATG4. Defect in Cvt pathway and autophagy. 1 Publication
Mutagenesisi117 – 1171R → M: Normal processing after G-116 by ATG4. 1 Publication

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Chaini1 – 116116Autophagy-related protein 8PRO_0000017242Add
BLAST
Propeptidei117 – 1171Removed in mature formPRO_0000017243

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Lipidationi116 – 1161Phosphatidylethanolamine amidated glycine1 Publication

Post-translational modificationi

The C-terminal Arg-117 residue of ATG8 is removed by ATG4 to expose Gly-116 at the C-terminus. This Gly-116 forms then a thioester bond with the 'Cys-507' of ATG7 (E1-like activating enzyme) before being transferred to the 'Cys-234' of ATG3 (the specific E2 conjugating enzyme), in order to be finally amidated with phosphatidylethanolamine. This lipid modification anchors ATG8 to membranes and can be reversed by ATG4, releasing soluble ATG8 (PubMed:11100732).1 Publication

Sites

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Sitei116 – 1172Cleavage; by ATG4

Keywords - PTMi

Lipoprotein

Proteomic databases

MaxQBiP38182.

Miscellaneous databases

PMAP-CutDBP38182.

Expressioni

Inductioni

Up-regulated upon starvation conditions. Expression is under the control of UME6 which acts along with a histone deacetylase complex including SIN3 and RPD3 to regulate negatively ATG8 levels and subsequent autophagic activity.2 Publications

Interactioni

Subunit structurei

Conjugation to phosphatidylethanolamine (PE) leads to homodimerization. Interacts with ATG1, ATG3, ATG4, ATG7, ATG12, ATG32, ATG34 and the C-terminal 10 residues domain of ATG19. Interacts also with the endoplasmic reticulum to Golgi v-SNARE protein BET1 and the vacuolar v-SNARE protein NYV1. Interacts with the UBX domain-containing protein SHP1.20 Publications

Binary interactionsi

WithEntry#Exp.IntActNotes
ATG1P531043EBI-2684,EBI-2657
ATG3P403444EBI-2684,EBI-3381
ATG4P538673EBI-2684,EBI-29160
ATG7P388624EBI-2684,EBI-2677
BET1P228042EBI-2684,EBI-3550
CUE5Q084124EBI-2684,EBI-37580
NBR1Q145967EBI-2684,EBI-742698From a different organism.
SQSTM1Q135013EBI-2684,EBI-307104From a different organism.

Protein-protein interaction databases

BioGridi32625. 172 interactions.
DIPiDIP-1197N.
IntActiP38182. 18 interactions.
MINTiMINT-391771.

Structurei

Secondary structure

1
117
Legend: HelixTurnBeta strand
Show more details
Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Helixi6 – 83Combined sources
Helixi11 – 2414Combined sources
Beta strandi26 – 3510Combined sources
Beta strandi37 – 393Combined sources
Beta strandi48 – 525Combined sources
Helixi57 – 6711Combined sources
Beta strandi76 – 805Combined sources
Beta strandi87 – 904Combined sources
Helixi91 – 988Combined sources
Beta strandi105 – 1117Combined sources

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
EntryMethodResolution (Å)ChainPositionsPDBsum
2KQ7NMR-A1-117[»]
2KWCNMR-A1-116[»]
2LI5NMR-A1-116[»]
2ZPNX-ray2.70A/B/C/D1-116[»]
3RUIX-ray1.91B1-116[»]
3VH3X-ray2.00B1-116[»]
3VH4X-ray2.65B1-116[»]
3VXWX-ray3.00A1-116[»]
ProteinModelPortaliP38182.
SMRiP38182. Positions 4-116.
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiP38182.

Family & Domainsi

Sequence similaritiesi

Belongs to the ATG8 family.Curated

Phylogenomic databases

GeneTreeiENSGT00390000012937.
HOGENOMiHOG000232034.
InParanoidiP38182.
KOiK08341.
OMAiSEHRCVE.
OrthoDBiEOG092C5HB8.

Family and domain databases

CDDicd01611. GABARAP. 1 hit.
InterProiIPR004241. Atg8-like.
IPR029071. Ubiquitin-rel_dom.
[Graphical view]
PANTHERiPTHR10969. PTHR10969. 1 hit.
PfamiPF02991. Atg8. 1 hit.
[Graphical view]
SUPFAMiSSF54236. SSF54236. 1 hit.

Sequencei

Sequence statusi: Complete.

Sequence processingi: The displayed sequence is further processed into a mature form.

P38182-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MKSTFKSEYP FEKRKAESER IADRFKNRIP VICEKAEKSD IPEIDKRKYL
60 70 80 90 100
VPADLTVGQF VYVIRKRIML PPEKAIFIFV NDTLPPTAAL MSAIYQEHKD
110
KDGFLYVTYS GENTFGR
Length:117
Mass (Da):13,627
Last modified:October 1, 1994 - v1
Checksum:i1246CEFF5A038819
GO

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
X79489 Genomic DNA. Translation: CAA56032.1.
Z35839 Genomic DNA. Translation: CAA84899.1.
AY692870 Genomic DNA. Translation: AAT92889.1.
BK006936 Genomic DNA. Translation: DAA07045.1.
PIRiS45432.
RefSeqiNP_009475.1. NM_001178318.1.

Genome annotation databases

EnsemblFungiiYBL078C; YBL078C; YBL078C.
GeneIDi852200.
KEGGisce:YBL078C.

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
X79489 Genomic DNA. Translation: CAA56032.1.
Z35839 Genomic DNA. Translation: CAA84899.1.
AY692870 Genomic DNA. Translation: AAT92889.1.
BK006936 Genomic DNA. Translation: DAA07045.1.
PIRiS45432.
RefSeqiNP_009475.1. NM_001178318.1.

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
EntryMethodResolution (Å)ChainPositionsPDBsum
2KQ7NMR-A1-117[»]
2KWCNMR-A1-116[»]
2LI5NMR-A1-116[»]
2ZPNX-ray2.70A/B/C/D1-116[»]
3RUIX-ray1.91B1-116[»]
3VH3X-ray2.00B1-116[»]
3VH4X-ray2.65B1-116[»]
3VXWX-ray3.00A1-116[»]
ProteinModelPortaliP38182.
SMRiP38182. Positions 4-116.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi32625. 172 interactions.
DIPiDIP-1197N.
IntActiP38182. 18 interactions.
MINTiMINT-391771.

Proteomic databases

MaxQBiP38182.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsemblFungiiYBL078C; YBL078C; YBL078C.
GeneIDi852200.
KEGGisce:YBL078C.

Organism-specific databases

EuPathDBiFungiDB:YBL078C.
SGDiS000000174. ATG8.

Phylogenomic databases

GeneTreeiENSGT00390000012937.
HOGENOMiHOG000232034.
InParanoidiP38182.
KOiK08341.
OMAiSEHRCVE.
OrthoDBiEOG092C5HB8.

Enzyme and pathway databases

BioCyciYEAST:G3O-28969-MONOMER.
ReactomeiR-SCE-1632852. Macroautophagy.

Miscellaneous databases

EvolutionaryTraceiP38182.
PMAP-CutDBP38182.
PROiP38182.

Family and domain databases

CDDicd01611. GABARAP. 1 hit.
InterProiIPR004241. Atg8-like.
IPR029071. Ubiquitin-rel_dom.
[Graphical view]
PANTHERiPTHR10969. PTHR10969. 1 hit.
PfamiPF02991. Atg8. 1 hit.
[Graphical view]
SUPFAMiSSF54236. SSF54236. 1 hit.
ProtoNetiSearch...

Entry informationi

Entry nameiATG8_YEAST
AccessioniPrimary (citable) accession number: P38182
Secondary accession number(s): D6VPS5
Entry historyi
Integrated into UniProtKB/Swiss-Prot: October 1, 1994
Last sequence update: October 1, 1994
Last modified: September 7, 2016
This is version 153 of the entry and version 1 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programFungal Protein Annotation Program

Miscellaneousi

Miscellaneous

Present with 2010 molecules/cell in log phase SD medium.1 Publication

Keywords - Technical termi

3D-structure, Complete proteome, Reference proteome

Documents

  1. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  2. SIMILARITY comments
    Index of protein domains and families
  3. Yeast
    Yeast (Saccharomyces cerevisiae): entries, gene names and cross-references to SGD
  4. Yeast chromosome II
    Yeast (Saccharomyces cerevisiae) chromosome II: entries and gene names

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.