ATG8_KLUMD
ID ATG8_KLUMD Reviewed; 124 AA.
AC W0THY6;
DT 25-APR-2018, integrated into UniProtKB/Swiss-Prot.
DT 19-MAR-2014, sequence version 1.
DT 25-MAY-2022, entry version 27.
DE RecName: Full=Autophagy-related protein 8 {ECO:0000303|PubMed:26442587};
DE AltName: Full=Autophagy-related ubiquitin-like modifier ATG8 {ECO:0000250|UniProtKB:P38182};
DE Flags: Precursor;
GN Name=ATG8 {ECO:0000303|PubMed:26442587}; ORFNames=KLMA_80372;
OS Kluyveromyces marxianus (strain DMKU3-1042 / BCC 29191 / NBRC 104275)
OS (Yeast) (Candida kefyr).
OC Eukaryota; Fungi; Dikarya; Ascomycota; Saccharomycotina; Saccharomycetes;
OC Saccharomycetales; Saccharomycetaceae; Kluyveromyces.
OX NCBI_TaxID=1003335;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=DMKU3-1042 / BCC 29191 / NBRC 104275;
RX PubMed=25834639; DOI=10.1186/s13068-015-0227-x;
RA Lertwattanasakul N., Kosaka T., Hosoyama A., Suzuki Y., Rodrussamee N.,
RA Matsutani M., Murata M., Fujimoto N., Suprayogi X., Tsuchikane K.,
RA Limtong S., Fujita N., Yamada M.;
RT "Genetic basis of the highly efficient yeast Kluyveromyces marxianus:
RT complete genome sequence and transcriptome analyses.";
RL Biotechnol. Biofuels 8:47-47(2015).
RN [2]
RP IDENTIFICATION, FUNCTION, DISRUPTION PHENOTYPE, SUBCELLULAR LOCATION, AND
RP MUTAGENESIS OF GLY-116 AND 117-GLY--LYS-124.
RX PubMed=26442587; DOI=10.1074/jbc.m115.684233;
RA Yamamoto H., Shima T., Yamaguchi M., Mochizuki Y., Hoshida H., Kakuta S.,
RA Kondo-Kakuta C., Noda N.N., Inagaki F., Itoh T., Akada R., Ohsumi Y.;
RT "The thermotolerant yeast Kluyveromyces marxianus is a useful organism for
RT structural and biochemical studies of autophagy.";
RL J. Biol. Chem. 290:29506-29518(2015).
CC -!- FUNCTION: Ubiquitin-like modifier involved in cytoplasm to vacuole
CC transport (Cvt) vesicles and autophagosomes formation
CC (PubMed:26442587). With ATG4, mediates the delivery of the vesicles and
CC autophagosomes to the vacuole via the microtubule cytoskeleton (By
CC similarity). Required for selective autophagic degradation of the
CC nucleus (nucleophagy) as well as for mitophagy which contributes to
CC regulate mitochondrial quantity and quality by eliminating the
CC mitochondria to a basal level to fulfill cellular energy requirements
CC and preventing excess ROS production (By similarity). Participates also
CC in membrane fusion events that take place in the early secretory
CC pathway (By similarity). Also involved in endoplasmic reticulum-
CC specific autophagic process and is essential for the survival of cells
CC subjected to severe ER stress (By similarity). The ATG8-PE conjugate
CC mediates tethering between adjacent membranes and stimulates membrane
CC hemifusion, leading to expansion of the autophagosomal membrane during
CC autophagy (By similarity). Moreover not only conjugation, but also
CC subsequent ATG8-PE deconjugation is an important step required to
CC facilitate multiple events during macroautophagy, and especially for
CC efficient autophagosome biogenesis, the assembly of ATG9-containing
CC tubulovesicular clusters into phagophores/autophagosomes, and for the
CC disassembly of PAS-associated ATG components (By similarity).
CC {ECO:0000250|UniProtKB:P38182, ECO:0000269|PubMed:26442587}.
CC -!- SUBUNIT: Conjugation to phosphatidylethanolamine (PE) leads to
CC homodimerization (By similarity). Interacts with ATG1, ATG3, ATG4, ATG7
CC and ATG12 (By similarity). {ECO:0000250|UniProtKB:P38182}.
CC -!- SUBCELLULAR LOCATION: Cytoplasmic vesicle, cvt vesicle membrane
CC {ECO:0000250|UniProtKB:P38182}; Lipid-anchor
CC {ECO:0000250|UniProtKB:P38182}. Cytoplasmic vesicle, autophagosome
CC membrane {ECO:0000250|UniProtKB:P38182}; Lipid-anchor
CC {ECO:0000250|UniProtKB:P38182}. Vacuole membrane
CC {ECO:0000269|PubMed:26442587}; Lipid-anchor
CC {ECO:0000250|UniProtKB:P38182}. Note=Membrane-associated through a
CC lipid anchor (By similarity). This association needs the 2 ubiquitin-
CC like systems required for cytoplasm to vacuole transport and autophagy
CC (By similarity). Localizes to both the isolation membrane (IM) and the
CC vacuole-isolation membrane contact site (VICS) during IM expansion (By
CC similarity). The IM is a membrane sac generated from the pre-
CC autophagosomal structure that ultimately expands to become a mature
CC autophagosome (By similarity). Accumulates atperivacuolar sites under
CC high temperature conditions (PubMed:26442587).
CC {ECO:0000250|UniProtKB:P38182, ECO:0000269|PubMed:26442587}.
CC -!- PTM: The C-terminal 8 residues of ATG8 are removed by ATG4 to expose
CC Gly-116 at the C-terminus (By similarity). This Gly-116 forms then a
CC thioester bond with the 'Cys-550' of ATG7 (E1-like activating enzyme)
CC before being transferred to the 'Cys-244' of ATG3 (the specific E2
CC conjugating enzyme), in order to be finally amidated with
CC phosphatidylethanolamine (By similarity). This lipid modification
CC anchors ATG8 to membranes and can be reversed by ATG4, releasing
CC soluble ATG8 (By similarity). {ECO:0000250|UniProtKB:P38182}.
CC -!- DISRUPTION PHENOTYPE: Blocks autophagic activity by impairing the
CC formation of autophagic bodies (PubMed:26442587).
CC {ECO:0000269|PubMed:26442587}.
CC -!- MISCELLANEOUS: Kluyveromyces marxianus proteins are shorter in length
CC and have a more ordered secondary structure than their S.cerevisiae
CC counterparts, which might contribute to the superior thermotolerance
CC and solubility (PubMed:26442587). K.marxianus could be therefore useful
CC as a new model organism for further elucidation of the molecular
CC details of autophagy (PubMed:26442587). {ECO:0000269|PubMed:26442587}.
CC -!- SIMILARITY: Belongs to the ATG8 family. {ECO:0000305}.
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DR EMBL; AP012220; BAO42683.1; -; Genomic_DNA.
DR AlphaFoldDB; W0THY6; -.
DR SMR; W0THY6; -.
DR EnsemblFungi; BAO42683; BAO42683; KLMA_80372.
DR OrthoDB; 1508198at2759; -.
DR Proteomes; UP000065495; Chromosome 8.
DR GO; GO:0000421; C:autophagosome membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0033110; C:Cvt vesicle membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0005829; C:cytosol; IEA:EnsemblFungi.
DR GO; GO:0019898; C:extrinsic component of membrane; IEA:EnsemblFungi.
DR GO; GO:0000329; C:fungal-type vacuole membrane; IEA:EnsemblFungi.
DR GO; GO:0000407; C:phagophore assembly site; IEA:EnsemblFungi.
DR GO; GO:0120095; C:vacuole-isolation membrane contact site; IEA:EnsemblFungi.
DR GO; GO:0008429; F:phosphatidylethanolamine binding; IEA:EnsemblFungi.
DR GO; GO:0031386; F:protein tag; IEA:EnsemblFungi.
DR GO; GO:0000422; P:autophagy of mitochondrion; IEA:EnsemblFungi.
DR GO; GO:0032258; P:cytoplasm to vacuole transport by the Cvt pathway; IEA:EnsemblFungi.
DR GO; GO:0006888; P:endoplasmic reticulum to Golgi vesicle-mediated transport; IEA:EnsemblFungi.
DR GO; GO:0044805; P:late nucleophagy; IEA:EnsemblFungi.
DR GO; GO:0061025; P:membrane fusion; IEA:EnsemblFungi.
DR GO; GO:0034727; P:piecemeal microautophagy of the nucleus; IEA:EnsemblFungi.
DR GO; GO:0034497; P:protein localization to phagophore assembly site; IEA:EnsemblFungi.
DR GO; GO:0071211; P:protein targeting to vacuole involved in autophagy; IEA:EnsemblFungi.
DR GO; GO:0031503; P:protein-containing complex localization; IEA:EnsemblFungi.
DR GO; GO:0016241; P:regulation of macroautophagy; IEA:EnsemblFungi.
DR GO; GO:1905153; P:regulation of membrane invagination; IEA:EnsemblFungi.
DR GO; GO:0061709; P:reticulophagy; IEA:EnsemblFungi.
DR InterPro; IPR004241; Atg8-like.
DR InterPro; IPR029071; Ubiquitin-like_domsf.
DR PANTHER; PTHR10969; PTHR10969; 1.
DR Pfam; PF02991; ATG8; 1.
DR SUPFAM; SSF54236; SSF54236; 1.
PE 1: Evidence at protein level;
KW Autophagy; Cytoplasmic vesicle; Lipoprotein; Membrane; Protein transport;
KW Transport; Vacuole.
FT CHAIN 1..124
FT /note="Autophagy-related protein 8"
FT /id="PRO_0000443891"
FT PROPEP 117..124
FT /note="Removed in mature form"
FT /evidence="ECO:0000250|UniProtKB:P38182"
FT /id="PRO_0000443892"
FT SITE 116..117
FT /note="Cleavage; by ATG4"
FT /evidence="ECO:0000250|UniProtKB:P38182,
FT ECO:0000305|PubMed:26442587"
FT LIPID 116
FT /note="Phosphatidylethanolamine amidated glycine"
FT /evidence="ECO:0000250|UniProtKB:P38182"
FT MUTAGEN 116
FT /note="G->A: In Atg8FA; prevents conjugation with
FT phosphatidylethanolamine (PE) and impairs the correct
FT localization to autophagic membranes."
FT /evidence="ECO:0000269|PubMed:26442587"
FT MUTAGEN 117..124
FT /note="Missing: In Atg8FG; bypasses the requirement for
FT cleavage by ATG4 to be localized to autophagic membranes."
FT /evidence="ECO:0000269|PubMed:26442587"
SQ SEQUENCE 124 AA; 14137 MW; 2E5BAF8E7A9464A3 CRC64;
MKSAFKSEFP FEKRKAESER IVQKFHNRIP VICERGGKSD IPDIDKRKYL VPGDLTVGQF
VYVIRKRIKL PAEKAIFIFV NDTLPPTAAL MSSIYQHHKD KDGFLYVSYS SENTFGGAGP
LLEK
