ATG4_YARLI
ID ATG4_YARLI Reviewed; 545 AA.
AC Q6CH28;
DT 26-APR-2005, integrated into UniProtKB/Swiss-Prot.
DT 16-AUG-2004, sequence version 1.
DT 03-AUG-2022, entry version 90.
DE RecName: Full=Probable cysteine protease ATG4;
DE EC=3.4.22.-;
DE AltName: Full=Autophagy-related protein 4;
GN Name=ATG4; OrderedLocusNames=YALI0A13277g;
OS Yarrowia lipolytica (strain CLIB 122 / E 150) (Yeast) (Candida lipolytica).
OC Eukaryota; Fungi; Dikarya; Ascomycota; Saccharomycotina; Saccharomycetes;
OC Saccharomycetales; Dipodascaceae; Yarrowia.
OX NCBI_TaxID=284591;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=CLIB 122 / E 150;
RX PubMed=15229592; DOI=10.1038/nature02579;
RA Dujon B., Sherman D., Fischer G., Durrens P., Casaregola S., Lafontaine I.,
RA de Montigny J., Marck C., Neuveglise C., Talla E., Goffard N., Frangeul L.,
RA Aigle M., Anthouard V., Babour A., Barbe V., Barnay S., Blanchin S.,
RA Beckerich J.-M., Beyne E., Bleykasten C., Boisrame A., Boyer J.,
RA Cattolico L., Confanioleri F., de Daruvar A., Despons L., Fabre E.,
RA Fairhead C., Ferry-Dumazet H., Groppi A., Hantraye F., Hennequin C.,
RA Jauniaux N., Joyet P., Kachouri R., Kerrest A., Koszul R., Lemaire M.,
RA Lesur I., Ma L., Muller H., Nicaud J.-M., Nikolski M., Oztas S.,
RA Ozier-Kalogeropoulos O., Pellenz S., Potier S., Richard G.-F.,
RA Straub M.-L., Suleau A., Swennen D., Tekaia F., Wesolowski-Louvel M.,
RA Westhof E., Wirth B., Zeniou-Meyer M., Zivanovic Y., Bolotin-Fukuhara M.,
RA Thierry A., Bouchier C., Caudron B., Scarpelli C., Gaillardin C.,
RA Weissenbach J., Wincker P., Souciet J.-L.;
RT "Genome evolution in yeasts.";
RL Nature 430:35-44(2004).
CC -!- FUNCTION: Cysteine protease that plays a key role in cytoplasm to
CC vacuole transport (Cvt) and autophagy by mediating both proteolytic
CC activation and delipidation of ATG8. Required for selective autophagic
CC degradation of the nucleus (nucleophagy) as well as for mitophagy which
CC contributes to regulate mitochondrial quantity and quality by
CC eliminating the mitochondria to a basal level to fulfill cellular
CC energy requirements and preventing excess ROS production. The protease
CC activity is required for proteolytic activation of ATG8: cleaves the C-
CC terminal amino acid of ATG8 to reveal a C-terminal glycine. ATG8
CC ubiquitin-like activity requires the exposure of the glycine at the C-
CC terminus for its conjugation to phosphatidylethanolamine (PE) and its
CC insertion to membranes, which is necessary for autophagy. The ATG8-PE
CC conjugate mediates tethering between adjacent membranes and stimulates
CC membrane hemifusion, leading to expansion of the autophagosomal
CC membrane during autophagy. In addition to the protease activity, also
CC catalyzes deconjugation of PE-conjugated forms of ATG8 during
CC macroautophagy: ATG8 delipidation is required to release the protein
CC from membranes, which facilitates multiple events during
CC macroautophagy, and especially for efficient autophagosome biogenesis,
CC the assembly of ATG9-containing tubulovesicular clusters into
CC phagophores/autophagosomes, and for the disassembly of PAS-associated
CC ATG components. ATG8 delipidation by ATG4 also recycles ATG8-PE
CC generated on inappropriate membranes to maintain a reservoir of
CC unlipidated ATG8 that is required for autophagosome formation at the
CC PAS. {ECO:0000250|UniProtKB:P53867}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=[protein]-C-terminal L-amino acid-glycyl-
CC phosphatidylethanolamide + H2O = [protein]-C-terminal L-amino acid-
CC glycine + a 1,2-diacyl-sn-glycero-3-phosphoethanolamine;
CC Xref=Rhea:RHEA:67548, Rhea:RHEA-COMP:17323, Rhea:RHEA-COMP:17324,
CC ChEBI:CHEBI:15377, ChEBI:CHEBI:64612, ChEBI:CHEBI:172940,
CC ChEBI:CHEBI:172941; Evidence={ECO:0000250|UniProtKB:P53867};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:67549;
CC Evidence={ECO:0000250|UniProtKB:P53867};
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000250|UniProtKB:P53867}. Nucleus
CC {ECO:0000250|UniProtKB:P53867}. Preautophagosomal structure
CC {ECO:0000250|UniProtKB:P53867}.
CC -!- SIMILARITY: Belongs to the peptidase C54 family. {ECO:0000305}.
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DR EMBL; CR382127; CAG83963.1; -; Genomic_DNA.
DR RefSeq; XP_500034.1; XM_500034.1.
DR AlphaFoldDB; Q6CH28; -.
DR SMR; Q6CH28; -.
DR STRING; 4952.CAG83963; -.
DR MEROPS; C54.001; -.
DR EnsemblFungi; CAG83963; CAG83963; YALI0_A13277g.
DR GeneID; 2906209; -.
DR KEGG; yli:YALI0A13277g; -.
DR VEuPathDB; FungiDB:YALI0_A13277g; -.
DR HOGENOM; CLU_021259_5_3_1; -.
DR InParanoid; Q6CH28; -.
DR OMA; SHYFFGF; -.
DR Proteomes; UP000001300; Chromosome A.
DR GO; GO:0005634; C:nucleus; IEA:UniProtKB-SubCell.
DR GO; GO:0000407; C:phagophore assembly site; IEA:UniProtKB-SubCell.
DR GO; GO:0008234; F:cysteine-type peptidase activity; IEA:UniProtKB-KW.
DR GO; GO:0006914; P:autophagy; IEA:UniProtKB-KW.
DR GO; GO:0015031; P:protein transport; IEA:UniProtKB-KW.
DR GO; GO:0006508; P:proteolysis; IEA:UniProtKB-KW.
DR InterPro; IPR038765; Papain-like_cys_pep_sf.
DR InterPro; IPR005078; Peptidase_C54.
DR PANTHER; PTHR22624; PTHR22624; 1.
DR Pfam; PF03416; Peptidase_C54; 1.
DR SUPFAM; SSF54001; SSF54001; 1.
PE 3: Inferred from homology;
KW Autophagy; Cytoplasm; Hydrolase; Nucleus; Protease; Protein transport;
KW Reference proteome; Thiol protease; Transport.
FT CHAIN 1..545
FT /note="Probable cysteine protease ATG4"
FT /id="PRO_0000215869"
FT REGION 156..181
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 459..545
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 158..181
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 523..545
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT ACT_SITE 120
FT /note="Nucleophile"
FT /evidence="ECO:0000250|UniProtKB:Q9Y4P1"
FT ACT_SITE 323
FT /evidence="ECO:0000250|UniProtKB:Q9Y4P1"
FT ACT_SITE 325
FT /evidence="ECO:0000250|UniProtKB:Q9Y4P1"
SQ SEQUENCE 545 AA; 60412 MW; C295E2B33E9E34FB CRC64;
MSLQRALQYL WDAEPHNTDH VTPLFCLGQV YDADTSLKEV NDDTEEDGIV VPLDTSNDTS
WPPDFLADVQ SRIWLSYRTG FPLIPKSDGS GTIHLGKLKN MIRGGGFDPR GYTSDVGWGC
MIRTSQSLLA NALLFRHLGR GWRWNKGDDF VYLSEGNTES RGGESRNGGA NKEQETAVSE
ETAVSEETII SWFLDSPDSP FSIHKFVRHG EKACSTPAGD WFGPSAAGSS IYALCNEFPD
SGLKVYYNGN GGGDVYEDEL LETGFPLLVL CGLRLGIDNV NPIYWDSLRQ MLSLPQSVGI
AGGRPFTSHY FFGFQGEQLF YLDPHQPKPA VKTTDKDTTS FHSSRIWKLH LKEMDPSMLV
GFYITSEADW ETFKGSLTAS KEKTSSQIVH IHPSRHNIPS FDEEDEYVSI GGASDDDFVD
VTKRARKVAA MTGNTGSGRS SPSILDSHLV TETRDIIESV PPRKRVDNDL TSAPVDVPKP
VQKRSQSHGD WEKVEEPEEE MVEVESMKGM QDNGCSAEYG SLVDRDAEAD DSTLSTETTD
RDWVV
