ATG4_CHAGB
ID ATG4_CHAGB Reviewed; 448 AA.
AC Q2HH40;
DT 05-FEB-2008, integrated into UniProtKB/Swiss-Prot.
DT 05-FEB-2008, sequence version 2.
DT 03-AUG-2022, entry version 63.
DE RecName: Full=Probable cysteine protease ATG4;
DE EC=3.4.22.-;
DE AltName: Full=Autophagy-related protein 4;
GN Name=ATG4; ORFNames=CHGG_00464;
OS Chaetomium globosum (strain ATCC 6205 / CBS 148.51 / DSM 1962 / NBRC 6347 /
OS NRRL 1970) (Soil fungus).
OC Eukaryota; Fungi; Dikarya; Ascomycota; Pezizomycotina; Sordariomycetes;
OC Sordariomycetidae; Sordariales; Chaetomiaceae; Chaetomium.
OX NCBI_TaxID=306901;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=ATCC 6205 / CBS 148.51 / DSM 1962 / NBRC 6347 / NRRL 1970;
RX PubMed=25720678; DOI=10.1128/genomea.00021-15;
RA Cuomo C.A., Untereiner W.A., Ma L.-J., Grabherr M., Birren B.W.;
RT "Draft genome sequence of the cellulolytic fungus Chaetomium globosum.";
RL Genome Announc. 3:E0002115-E0002115(2015).
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=EAQ92229.1; Type=Erroneous gene model prediction; Evidence={ECO:0000305};
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DR EMBL; CH408029; EAQ92229.1; ALT_SEQ; Genomic_DNA.
DR RefSeq; XP_001219685.1; XM_001219684.1.
DR AlphaFoldDB; Q2HH40; -.
DR SMR; Q2HH40; -.
DR STRING; 38033.XP_001219685.1; -.
DR MEROPS; C54.001; -.
DR EnsemblFungi; EAQ92229; EAQ92229; CHGG_00464.
DR GeneID; 4387937; -.
DR eggNOG; KOG2674; Eukaryota.
DR HOGENOM; CLU_021259_5_1_1; -.
DR InParanoid; Q2HH40; -.
DR OrthoDB; 431748at2759; -.
DR Proteomes; UP000001056; 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..448
FT /note="Probable cysteine protease ATG4"
FT /id="PRO_0000317836"
FT REGION 69..90
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 74..90
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT ACT_SITE 168
FT /note="Nucleophile"
FT /evidence="ECO:0000250|UniProtKB:Q9Y4P1"
FT ACT_SITE 341
FT /evidence="ECO:0000250|UniProtKB:Q9Y4P1"
FT ACT_SITE 343
FT /evidence="ECO:0000250|UniProtKB:Q9Y4P1"
SQ SEQUENCE 448 AA; 49557 MW; 75CFF184889E94E4 CRC64;
MEVALAVGAE ASRVSRRILQ KIWDPEPIND RDSNEPVWCL GRSYKLAPET PSPVTTATSP
VDGAIDAAPA PIATPGTTNR QAIDTPPDSL ASSFDSSLAY DNRNQDSGWP PAFLDDFGSR
IWMTYRTGFE PIPRSTDPKA ASALSFTMRL KTSFGDQTGF SSDTGWGCMI RSGQSLLANA
LLISQLGRDW RRTTDPGAER NIVALFADDA RAPYSLQNFV KHGAIACGKH PGEWFGPSAT
ARCIQALADQ HESSLRIYST GDLPDVYEDS FLATARPDGE TFHPTLILVC TRLGIDKINP
VYEEALISTL QMEQSIGIAG GRPSSSHYFV GVQRQWLFYL DPHHPRPALQ YRENPLNYTL
EELDSCHTRR LRYLHVEDMD PSMLIGFLIQ DEDDWDMWKS AVKHVQGKSI INVSRHDPAR
GMGGARAEAI DEVETLSDDD DVDTVLEQ
