ATG4_PENRW
ID ATG4_PENRW Reviewed; 401 AA.
AC A7KAL5; B6HEZ1;
DT 05-FEB-2008, integrated into UniProtKB/Swiss-Prot.
DT 11-SEP-2007, sequence version 1.
DT 03-AUG-2022, entry version 72.
DE RecName: Full=Probable cysteine protease atg4;
DE EC=3.4.22.-;
DE AltName: Full=Autophagy-related protein 4;
GN Name=atg4; ORFNames=Pc20g08610;
OS Penicillium rubens (strain ATCC 28089 / DSM 1075 / NRRL 1951 / Wisconsin
OS 54-1255) (Penicillium chrysogenum).
OC Eukaryota; Fungi; Dikarya; Ascomycota; Pezizomycotina; Eurotiomycetes;
OC Eurotiomycetidae; Eurotiales; Aspergillaceae; Penicillium;
OC Penicillium chrysogenum species complex.
OX NCBI_TaxID=500485;
RN [1]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND FUNCTION.
RX PubMed=17204848; DOI=10.4161/auto.3595;
RA Meijer W.H., van der Klei I.J., Veenhuis M., Kiel J.A.K.W.;
RT "ATG genes involved in non-selective autophagy are conserved from yeast to
RT man, but the selective Cvt and pexophagy pathways also require organism-
RT specific genes.";
RL Autophagy 3:106-116(2007).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=ATCC 28089 / DSM 1075 / NRRL 1951 / Wisconsin 54-1255;
RX PubMed=18820685; DOI=10.1038/nbt.1498;
RA van den Berg M.A., Albang R., Albermann K., Badger J.H., Daran J.-M.,
RA Driessen A.J.M., Garcia-Estrada C., Fedorova N.D., Harris D.M.,
RA Heijne W.H.M., Joardar V.S., Kiel J.A.K.W., Kovalchuk A., Martin J.F.,
RA Nierman W.C., Nijland J.G., Pronk J.T., Roubos J.A., van der Klei I.J.,
RA van Peij N.N.M.E., Veenhuis M., von Doehren H., Wagner C., Wortman J.R.,
RA Bovenberg R.A.L.;
RT "Genome sequencing and analysis of the filamentous fungus Penicillium
RT chrysogenum.";
RL Nat. Biotechnol. 26:1161-1168(2008).
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 (PubMed:17204848). Required for
CC selective autophagic degradation of the nucleus (nucleophagy) as well
CC as for mitophagy which contributes to regulate mitochondrial quantity
CC and quality by eliminating the mitochondria to a basal level to fulfill
CC cellular energy requirements and preventing excess ROS production. The
CC protease activity is required for proteolytic activation of ATG8:
CC cleaves the C-terminal amino acid of ATG8 to reveal a C-terminal
CC glycine. ATG8 ubiquitin-like activity requires the exposure of the
CC glycine at the C-terminus for its conjugation to
CC phosphatidylethanolamine (PE) and its insertion to membranes, which is
CC necessary for autophagy. The ATG8-PE conjugate mediates tethering
CC between adjacent membranes and stimulates membrane hemifusion, leading
CC to expansion of the autophagosomal membrane during autophagy. In
CC addition to the protease activity, also catalyzes deconjugation of PE-
CC conjugated forms of ATG8 during macroautophagy: ATG8 delipidation is
CC required to release the protein from membranes, which facilitates
CC multiple events during macroautophagy, and especially for efficient
CC autophagosome biogenesis, the assembly of ATG9-containing
CC tubulovesicular clusters into phagophores/autophagosomes, and for the
CC disassembly of PAS-associated ATG components. ATG8 delipidation by ATG4
CC also recycles ATG8-PE generated on inappropriate membranes to maintain
CC a reservoir of unlipidated ATG8 that is required for autophagosome
CC formation at the PAS (By similarity). {ECO:0000250|UniProtKB:P53867,
CC ECO:0000269|PubMed:17204848}.
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; EF107737; ABO31075.1; -; Genomic_DNA.
DR EMBL; AM920435; CAP86190.1; -; Genomic_DNA.
DR RefSeq; XP_002563384.1; XM_002563338.1.
DR AlphaFoldDB; A7KAL5; -.
DR SMR; A7KAL5; -.
DR STRING; 1108849.XP_002563384.1; -.
DR MEROPS; C54.001; -.
DR EnsemblFungi; CAP86190; CAP86190; PCH_Pc20g08610.
DR GeneID; 8304200; -.
DR KEGG; pcs:Pc20g08610; -.
DR VEuPathDB; FungiDB:PCH_Pc20g08610; -.
DR eggNOG; KOG2674; Eukaryota.
DR HOGENOM; CLU_021259_5_1_1; -.
DR OMA; CHTRRIR; -.
DR OrthoDB; 431748at2759; -.
DR BioCyc; PCHR:PC20G08610-MON; -.
DR Proteomes; UP000000724; Contig Pc00c20.
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..401
FT /note="Probable cysteine protease atg4"
FT /id="PRO_0000317840"
FT REGION 37..65
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 49..65
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT ACT_SITE 126
FT /note="Nucleophile"
FT /evidence="ECO:0000250|UniProtKB:P53867"
FT ACT_SITE 300
FT /evidence="ECO:0000250|UniProtKB:Q9Y4P1"
FT ACT_SITE 302
FT /evidence="ECO:0000250|UniProtKB:Q9Y4P1"
SQ SEQUENCE 401 AA; 45302 MW; 976AD8C6EED0B518 CRC64;
MTMDMEKCKR IVQYFWDPEP RNDVPAASIW CLGREYAPSQ PPSDPASNNP RSPSRQPNAS
TLNDTTWPKA FLSDFGSRIW ITYRSNFTPI PRTKTPEATS SMTLGVRLRS QLMDPQGFTS
DTGWGCMIRS GQSLLANTFS VLLLGRDWRR GEKVEEESKL ISMFADHPEA PFSIHRFVNR
GAESCGKYPG EWFGPSATAK CIQLLSTQSE VPQLRVYLTN DTSDVYEDKF AHVAHDESGR
IQPTLILIGT RLGIDNVTPA YWDGLRAALT YPQSVGIAGG RPSASHYFVG AQDCHLFFLD
PHTTRPATLY RPDGLYTQEE LDSYYTSRLR RIHIKDMDPS MLIGFLVKDE DDWADWKKRI
RSTPGQPIVH IFPSQHQPDH GHGRAEALDE VEALDDSDEM E
