ATG4_PICST
ID ATG4_PICST Reviewed; 514 AA.
AC A3LQU0;
DT 05-FEB-2008, integrated into UniProtKB/Swiss-Prot.
DT 24-JUL-2007, sequence version 2.
DT 03-AUG-2022, entry version 68.
DE RecName: Full=Probable cysteine protease ATG4;
DE EC=3.4.22.-;
DE AltName: Full=Autophagy-related protein 4;
GN Name=ATG4; ORFNames=PICST_30446;
OS Scheffersomyces stipitis (strain ATCC 58785 / CBS 6054 / NBRC 10063 / NRRL
OS Y-11545) (Yeast) (Pichia stipitis).
OC Eukaryota; Fungi; Dikarya; Ascomycota; Saccharomycotina; Saccharomycetes;
OC Saccharomycetales; Debaryomycetaceae; Scheffersomyces.
OX NCBI_TaxID=322104;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=ATCC 58785 / CBS 6054 / NBRC 10063 / NRRL Y-11545;
RX PubMed=17334359; DOI=10.1038/nbt1290;
RA Jeffries T.W., Grigoriev I.V., Grimwood J., Laplaza J.M., Aerts A.,
RA Salamov A., Schmutz J., Lindquist E., Dehal P., Shapiro H., Jin Y.-S.,
RA Passoth V., Richardson P.M.;
RT "Genome sequence of the lignocellulose-bioconverting and xylose-fermenting
RT yeast Pichia stipitis.";
RL Nat. Biotechnol. 25:319-326(2007).
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; CP000497; ABN65267.2; -; Genomic_DNA.
DR RefSeq; XP_001383296.2; XM_001383259.1.
DR AlphaFoldDB; A3LQU0; -.
DR SMR; A3LQU0; -.
DR STRING; 4924.XP_001383296.2; -.
DR MEROPS; C54.001; -.
DR EnsemblFungi; ABN65267; ABN65267; PICST_30446.
DR GeneID; 4837900; -.
DR KEGG; pic:PICST_30446; -.
DR eggNOG; KOG2674; Eukaryota.
DR HOGENOM; CLU_021259_5_2_1; -.
DR InParanoid; A3LQU0; -.
DR OMA; KILHFHP; -.
DR OrthoDB; 431748at2759; -.
DR Proteomes; UP000002258; Chromosome 3.
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..514
FT /note="Probable cysteine protease ATG4"
FT /id="PRO_0000317844"
FT REGION 1..28
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 61..84
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 461..514
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT ACT_SITE 166
FT /note="Nucleophile"
FT /evidence="ECO:0000250|UniProtKB:Q9Y4P1"
FT ACT_SITE 336
FT /evidence="ECO:0000250|UniProtKB:Q9Y4P1"
FT ACT_SITE 338
FT /evidence="ECO:0000250|UniProtKB:Q9Y4P1"
SQ SEQUENCE 514 AA; 57380 MW; ECB804F40801FAE3 CRC64;
MAREDASVPR SHDSADASPN STAKEIPVPQ PPLLNLNLNL NMNSGFNLSN WWHQITSIEA
DSSDDRNNNN SNNGINAAES DSAQSQPIVV LGHSYQTTEE AHEDIIKKLC LTYRYGFERI
PRAVNGPSPL SFMQSVIFSK SLLYNLQNFN NFIEKENFTT DVGWGCMIRT SQSLLANTFV
RLLDKQSDII ALFNDTYLAP FSLHNFIRVA SSSPLKVKPG EWFGPNAASL SIKRLCDGYY
DNSTSETILP RINVLISEST DLYDSQIAQL LEPSTETKGL LVLLPVRLGI DSINSYYFSS
LLHLLSLEQS VGIAGGKPSS SFYFFGYQDN SLIYMDPHSA QIFSSDIDMS TYYATRYQRV
DIGKLDPSML IGVFIRDLTS YENFKKSCLD AANKIVHFHA TERSTVPESR RKNSEFVNIN
RSDLKDEDYI NIDRVNRLDS TDDFIDLGDD YVETNTNLEE ATPSAEDTVP VSTLSASESE
ITTSSYETPT SKDDNSSRAS LDVVVLDTTG EQQE
