ATG4_DEBHA
ID ATG4_DEBHA Reviewed; 492 AA.
AC Q6BYP8;
DT 26-APR-2005, integrated into UniProtKB/Swiss-Prot.
DT 16-DEC-2008, sequence version 2.
DT 03-AUG-2022, entry version 79.
DE RecName: Full=Probable cysteine protease ATG4;
DE EC=3.4.22.-;
DE AltName: Full=Autophagy-related protein 4;
GN Name=ATG4; OrderedLocusNames=DEHA2A07832g;
OS Debaryomyces hansenii (strain ATCC 36239 / CBS 767 / BCRC 21394 / JCM 1990
OS / NBRC 0083 / IGC 2968) (Yeast) (Torulaspora hansenii).
OC Eukaryota; Fungi; Dikarya; Ascomycota; Saccharomycotina; Saccharomycetes;
OC Saccharomycetales; Debaryomycetaceae; Debaryomyces.
OX NCBI_TaxID=284592;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=ATCC 36239 / CBS 767 / BCRC 21394 / JCM 1990 / NBRC 0083 / IGC 2968;
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; CR382133; CAG84627.2; -; Genomic_DNA.
DR RefSeq; XP_456671.2; XM_456671.1.
DR AlphaFoldDB; Q6BYP8; -.
DR SMR; Q6BYP8; -.
DR STRING; 4959.XP_456671.2; -.
DR MEROPS; C54.001; -.
DR EnsemblFungi; CAG84627; CAG84627; DEHA2A07832g.
DR GeneID; 2899646; -.
DR KEGG; dha:DEHA2A07832g; -.
DR VEuPathDB; FungiDB:DEHA2A07832g; -.
DR eggNOG; KOG2674; Eukaryota.
DR HOGENOM; CLU_021259_5_2_1; -.
DR InParanoid; Q6BYP8; -.
DR OMA; KILHFHP; -.
DR OrthoDB; 431748at2759; -.
DR Proteomes; UP000000599; 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..492
FT /note="Probable cysteine protease ATG4"
FT /id="PRO_0000215861"
FT REGION 454..492
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 472..492
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT ACT_SITE 151
FT /note="Nucleophile"
FT /evidence="ECO:0000250|UniProtKB:Q9Y4P1"
FT ACT_SITE 330
FT /evidence="ECO:0000250|UniProtKB:Q9Y4P1"
FT ACT_SITE 332
FT /evidence="ECO:0000250|UniProtKB:Q9Y4P1"
SQ SEQUENCE 492 AA; 55840 MW; D1EC3A3AC3E1074A CRC64;
MSNRDSSEHG DSSNKIASNE CNEATKLGFN FTQLWSQITT TYSLIDRNDS NMFNRDERVE
SEQEKKSVVI LGKKYDDISV DDGVIEQDIY SKIWLTYRTG FEPIAKCLDG PQPLSFVQSM
VFNRNPISST FNNFHGLLDN DNFTTDVGWG CMIRTSQALL ANTYQLLFLG RGFSYGRDRS
PRHDEIIDMF MDEPRAPFSL HNFIKVASES PLKVKPGQWF GPNAASLSIK RLCDNVYESN
GTGRVKVVIS ESSNLYDDII TQMFTTLNPV PDAILVLLPV RLGIDKVNPL YHASVLELLA
LRQSVGIAGG KPSSSFYFFG YKGNDLLYLD PHYPQFVRNK TSVYDTYHTN SYQKLSVDDM
DPSMMIGILI KDINDYEDFK SSCTKSSNKI LHFHPTSEKA DRRGSLSEFK RKNSEFVCIE
SKDVQRREDF ITIDNVSRDD LNNMEGFIDM ADEFDSEIDQ NNKDDNFDDD EPVNVSQTSI
GEEYTSTAGS RP
