ATG4_VANPO
ID ATG4_VANPO Reviewed; 411 AA.
AC A7TQN1;
DT 05-FEB-2008, integrated into UniProtKB/Swiss-Prot.
DT 02-OCT-2007, sequence version 1.
DT 03-AUG-2022, entry version 65.
DE RecName: Full=Probable cysteine protease ATG4;
DE EC=3.4.22.-;
DE AltName: Full=Autophagy-related protein 4;
GN Name=ATG4; ORFNames=Kpol_1015p1;
OS Vanderwaltozyma polyspora (strain ATCC 22028 / DSM 70294 / BCRC 21397 / CBS
OS 2163 / NBRC 10782 / NRRL Y-8283 / UCD 57-17) (Kluyveromyces polysporus).
OC Eukaryota; Fungi; Dikarya; Ascomycota; Saccharomycotina; Saccharomycetes;
OC Saccharomycetales; Saccharomycetaceae; Vanderwaltozyma.
OX NCBI_TaxID=436907;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=ATCC 22028 / DSM 70294 / BCRC 21397 / CBS 2163 / NBRC 10782 / NRRL
RC Y-8283 / UCD 57-17;
RX PubMed=17494770; DOI=10.1073/pnas.0608218104;
RA Scannell D.R., Frank A.C., Conant G.C., Byrne K.P., Woolfit M., Wolfe K.H.;
RT "Independent sorting-out of thousands of duplicated gene pairs in two yeast
RT species descended from a whole-genome duplication.";
RL Proc. Natl. Acad. Sci. U.S.A. 104:8397-8402(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; DS480461; EDO15412.1; -; Genomic_DNA.
DR RefSeq; XP_001643270.1; XM_001643220.1.
DR AlphaFoldDB; A7TQN1; -.
DR SMR; A7TQN1; -.
DR STRING; 436907.A7TQN1; -.
DR MEROPS; C54.001; -.
DR EnsemblFungi; EDO15412; EDO15412; Kpol_1015p1.
DR GeneID; 5543503; -.
DR KEGG; vpo:Kpol_1015p1; -.
DR eggNOG; KOG2674; Eukaryota.
DR HOGENOM; CLU_021259_5_3_1; -.
DR InParanoid; A7TQN1; -.
DR OMA; NREHHEA; -.
DR OrthoDB; 431748at2759; -.
DR PhylomeDB; A7TQN1; -.
DR Proteomes; UP000000267; 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..411
FT /note="Probable cysteine protease ATG4"
FT /id="PRO_0000317846"
FT REGION 390..411
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT ACT_SITE 135
FT /note="Nucleophile"
FT /evidence="ECO:0000250|UniProtKB:Q9Y4P1"
FT ACT_SITE 310
FT /evidence="ECO:0000250|UniProtKB:Q9Y4P1"
FT ACT_SITE 312
FT /evidence="ECO:0000250|UniProtKB:Q9Y4P1"
SQ SEQUENCE 411 AA; 46394 MW; 058E75B3C4B1F68F CRC64;
MELSQKEIGL DRSKDDNGLS SNDYVVLGIH YPIDSDDDKV VELANKRSNS AGGSIGMFQQ
FFNKVEEFDY HPGFLSDVIS RIHFTYRTKF IPIARSDDGP SPLRINFLIG DNPFNAIENA
IYNPNCFNTD IGWGCMIRTG QSLLANAIQI AILGREFRVN DGDVNEQERK IISWFMDTPD
EPFSLHNFVK KGCELSSKKP GEWFGPAATS RSIQSLVEQF PDCGIDRCIV SVSSADIFKD
EINDIFKNKR YSNILLLMGV KLGVDKVNEY YLKDIRKILE SRYSVGISGG RPSSSLYFFG
YQDDTLLYFD PHKPQPSTIE SLLETCHTDN FDKINISDMD PSMLIGVLLQ GEDDWQSWSN
EVFDSKIINI LNSRNDVTIA EDSMSLEETL EPPDNEYVDL GPMSQQLNGS P
