ID   ATG4_SCLS1              Reviewed;         439 AA.
AC   A7F045;
DT   05-FEB-2008, integrated into UniProtKB/Swiss-Prot.
DT   05-FEB-2008, sequence version 2.
DT   03-AUG-2022, entry version 73.
DE   RecName: Full=Probable cysteine protease atg4;
DE            EC=3.4.22.-;
DE   AltName: Full=Autophagy-related protein 4;
GN   Name=atg4; ORFNames=SS1G_10962;
OS   Sclerotinia sclerotiorum (strain ATCC 18683 / 1980 / Ss-1) (White mold)
OS   (Whetzelinia sclerotiorum).
OC   Eukaryota; Fungi; Dikarya; Ascomycota; Pezizomycotina; Leotiomycetes;
OC   Helotiales; Sclerotiniaceae; Sclerotinia.
OX   NCBI_TaxID=665079;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC   STRAIN=ATCC 18683 / 1980 / Ss-1;
RX   PubMed=21876677; DOI=10.1371/journal.pgen.1002230;
RA   Amselem J., Cuomo C.A., van Kan J.A.L., Viaud M., Benito E.P., Couloux A.,
RA   Coutinho P.M., de Vries R.P., Dyer P.S., Fillinger S., Fournier E.,
RA   Gout L., Hahn M., Kohn L., Lapalu N., Plummer K.M., Pradier J.-M.,
RA   Quevillon E., Sharon A., Simon A., ten Have A., Tudzynski B., Tudzynski P.,
RA   Wincker P., Andrew M., Anthouard V., Beever R.E., Beffa R., Benoit I.,
RA   Bouzid O., Brault B., Chen Z., Choquer M., Collemare J., Cotton P.,
RA   Danchin E.G., Da Silva C., Gautier A., Giraud C., Giraud T., Gonzalez C.,
RA   Grossetete S., Gueldener U., Henrissat B., Howlett B.J., Kodira C.,
RA   Kretschmer M., Lappartient A., Leroch M., Levis C., Mauceli E.,
RA   Neuveglise C., Oeser B., Pearson M., Poulain J., Poussereau N.,
RA   Quesneville H., Rascle C., Schumacher J., Segurens B., Sexton A., Silva E.,
RA   Sirven C., Soanes D.M., Talbot N.J., Templeton M., Yandava C., Yarden O.,
RA   Zeng Q., Rollins J.A., Lebrun M.-H., Dickman M.;
RT   "Genomic analysis of the necrotrophic fungal pathogens Sclerotinia
RT   sclerotiorum and Botrytis cinerea.";
RL   PLoS Genet. 7:E1002230-E1002230(2011).
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}.
CC   -!- SEQUENCE CAUTION:
CC       Sequence=EDN95087.1; Type=Erroneous gene model prediction; Evidence={ECO:0000305};
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DR   EMBL; CH476637; EDN95087.1; ALT_SEQ; Genomic_DNA.
DR   RefSeq; XP_001587722.1; XM_001587672.1.
DR   AlphaFoldDB; A7F045; -.
DR   SMR; A7F045; -.
DR   STRING; 665079.A7F045; -.
DR   MEROPS; C54.001; -.
DR   GeneID; 5484186; -.
DR   KEGG; ssl:SS1G_10962; -.
DR   VEuPathDB; FungiDB:sscle_12g089570; -.
DR   eggNOG; KOG2674; Eukaryota.
DR   InParanoid; A7F045; -.
DR   Proteomes; UP000001312; Unassembled WGS sequence.
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..439
FT                   /note="Probable cysteine protease atg4"
FT                   /id="PRO_0000317845"
FT   REGION          65..91
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   ACT_SITE        158
FT                   /note="Nucleophile"
FT                   /evidence="ECO:0000250|UniProtKB:Q9Y4P1"
FT   ACT_SITE        332
FT                   /evidence="ECO:0000250|UniProtKB:Q9Y4P1"
FT   ACT_SITE        334
FT                   /evidence="ECO:0000250|UniProtKB:Q9Y4P1"
SQ   SEQUENCE   439 AA;  48728 MW;  61F6821B825241AB CRC64;
     MTTVDIGRYK RLVQYFWDPE PTNNIASKSP IWCLGEEYLV SDKSSPSAVT ESPPKEGGYL
     LAQSLSTTET TTPPDSTVGS LESSSEYDNC DTASTDGGWP TAFLDDFEAK IWLTYRSNFP
     AIAKSQDPKA LSAMSLSVRL RSQLVDQGGF TSDTGWGCMI RSGQSLLANA LLTLRMGREW
     RRGSSSNEER KILSLFADDP RAPYSIHKFV EHGASACGKH PGEWFGPSAA ARCIQALTNS
     QVESELRVYI TGDGSDVYED TFMSIAKPNS TKFTPTLILV GTRLGLDKIT PVYWEALKSS
     LQMPQSVGIA GGRPSSSHYF IGVQESDFFY LDPHQTRPAL PFNDNVEDYT PEDIDSCHTR
     RLRRLHIKEM DPSMLIAFLI RDENDWKDWR RAVREVQGKG VIHVADRDPA LHGLGAERDG
     AIDEVETFDD DDDDTVLNG