ATG4_PICGU
ID ATG4_PICGU Reviewed; 402 AA.
AC A5DEF7;
DT 05-FEB-2008, integrated into UniProtKB/Swiss-Prot.
DT 10-FEB-2009, sequence version 2.
DT 03-AUG-2022, entry version 61.
DE RecName: Full=Probable cysteine protease ATG4;
DE EC=3.4.22.-;
DE AltName: Full=Autophagy-related protein 4;
GN Name=ATG4; ORFNames=PGUG_01658;
OS Meyerozyma guilliermondii (strain ATCC 6260 / CBS 566 / DSM 6381 / JCM 1539
OS / NBRC 10279 / NRRL Y-324) (Yeast) (Candida guilliermondii).
OC Eukaryota; Fungi; Dikarya; Ascomycota; Saccharomycotina; Saccharomycetes;
OC Saccharomycetales; Debaryomycetaceae; Meyerozyma.
OX NCBI_TaxID=294746;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=ATCC 6260 / CBS 566 / DSM 6381 / JCM 1539 / NBRC 10279 / NRRL Y-324;
RX PubMed=19465905; DOI=10.1038/nature08064;
RA Butler G., Rasmussen M.D., Lin M.F., Santos M.A.S., Sakthikumar S.,
RA Munro C.A., Rheinbay E., Grabherr M., Forche A., Reedy J.L., Agrafioti I.,
RA Arnaud M.B., Bates S., Brown A.J.P., Brunke S., Costanzo M.C.,
RA Fitzpatrick D.A., de Groot P.W.J., Harris D., Hoyer L.L., Hube B.,
RA Klis F.M., Kodira C., Lennard N., Logue M.E., Martin R., Neiman A.M.,
RA Nikolaou E., Quail M.A., Quinn J., Santos M.C., Schmitzberger F.F.,
RA Sherlock G., Shah P., Silverstein K.A.T., Skrzypek M.S., Soll D.,
RA Staggs R., Stansfield I., Stumpf M.P.H., Sudbery P.E., Srikantha T.,
RA Zeng Q., Berman J., Berriman M., Heitman J., Gow N.A.R., Lorenz M.C.,
RA Birren B.W., Kellis M., Cuomo C.A.;
RT "Evolution of pathogenicity and sexual reproduction in eight Candida
RT genomes.";
RL Nature 459:657-662(2009).
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; CH408156; EDK37561.2; -; Genomic_DNA.
DR RefSeq; XP_001485988.1; XM_001485938.1.
DR AlphaFoldDB; A5DEF7; -.
DR SMR; A5DEF7; -.
DR STRING; 4929.XP_001485988.1; -.
DR MEROPS; C54.001; -.
DR EnsemblFungi; EDK37561; EDK37561; PGUG_01658.
DR GeneID; 5127478; -.
DR KEGG; pgu:PGUG_01658; -.
DR VEuPathDB; FungiDB:PGUG_01658; -.
DR eggNOG; KOG2674; Eukaryota.
DR HOGENOM; CLU_021259_5_2_1; -.
DR InParanoid; A5DEF7; -.
DR OMA; CHTRRIR; -.
DR OrthoDB; 431748at2759; -.
DR Proteomes; UP000001997; 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..402
FT /note="Probable cysteine protease ATG4"
FT /id="PRO_0000317843"
FT REGION 1..38
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT ACT_SITE 144
FT /note="Nucleophile"
FT /evidence="ECO:0000250|UniProtKB:Q9Y4P1"
FT ACT_SITE 299
FT /evidence="ECO:0000250|UniProtKB:Q9Y4P1"
FT ACT_SITE 301
FT /evidence="ECO:0000250|UniProtKB:Q9Y4P1"
SQ SEQUENCE 402 AA; 44844 MW; 7F752A539A1E55FE CRC64;
MTWDTKNQFE TTKTSQELPA TSQDHISDNK MNSEPSHRLS QFWSSLTRSS SESITAEPVV
ILGHTYREGD RDREGDSEVQ KQVKKRYWMS YRSGFEPIKK HEDGPSPLSF VQSMIFNKNV
GNTFANIHSL VDNDNFTTDV GWGCMIRTSQ SVLANAIDRA GYEVDVELFA DTSSAAFSLH
NFVKVASDSP LRVRPGQWFG PSAASLSIKR LCEARNSSTN VPLSVLVCES GDIYDDQIQT
FPVLLLLPLR LGIDHVNNVY HSSLLQLLEV PQSAGIAGGK PSSSLYFFGY QGTSLLYLDP
HYPQNVSAGV GSYHSSSYQK LDISDMDPSM MAGIVLKNNE DYTDLKRRTT GNKIIHFHEA
RNYNDYVEVE REDFIDLGQN NRSATAGAEA DFDSESSMVI VD
