ATG4_PHANO
ID ATG4_PHANO Reviewed; 467 AA.
AC Q0U199;
DT 05-FEB-2008, integrated into UniProtKB/Swiss-Prot.
DT 05-SEP-2006, sequence version 1.
DT 03-AUG-2022, entry version 70.
DE RecName: Full=Probable cysteine protease ATG4;
DE EC=3.4.22.-;
DE AltName: Full=Autophagy-related protein 4;
GN Name=ATG4; ORFNames=SNOG_14613;
OS Phaeosphaeria nodorum (strain SN15 / ATCC MYA-4574 / FGSC 10173) (Glume
OS blotch fungus) (Parastagonospora nodorum).
OC Eukaryota; Fungi; Dikarya; Ascomycota; Pezizomycotina; Dothideomycetes;
OC Pleosporomycetidae; Pleosporales; Pleosporineae; Phaeosphaeriaceae;
OC Parastagonospora.
OX NCBI_TaxID=321614;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=SN15 / ATCC MYA-4574 / FGSC 10173;
RX PubMed=18024570; DOI=10.1105/tpc.107.052829;
RA Hane J.K., Lowe R.G.T., Solomon P.S., Tan K.-C., Schoch C.L.,
RA Spatafora J.W., Crous P.W., Kodira C.D., Birren B.W., Galagan J.E.,
RA Torriani S.F.F., McDonald B.A., Oliver R.P.;
RT "Dothideomycete-plant interactions illuminated by genome sequencing and EST
RT analysis of the wheat pathogen Stagonospora nodorum.";
RL Plant Cell 19:3347-3368(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}.
CC -!- SEQUENCE CAUTION:
CC Sequence=EAT78153.2; Type=Erroneous gene model prediction; Evidence={ECO:0000305};
CC ---------------------------------------------------------------------------
CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms
CC Distributed under the Creative Commons Attribution (CC BY 4.0) License
CC ---------------------------------------------------------------------------
DR EMBL; CH445356; EAT78153.2; ALT_SEQ; Genomic_DNA.
DR RefSeq; XP_001804795.1; XM_001804743.1.
DR AlphaFoldDB; Q0U199; -.
DR SMR; Q0U199; -.
DR STRING; 321614.Q0U199; -.
DR MEROPS; C54.001; -.
DR GeneID; 5981720; -.
DR KEGG; pno:SNOG_14613; -.
DR eggNOG; KOG2674; Eukaryota.
DR InParanoid; Q0U199; -.
DR OMA; CHTRRIR; -.
DR OrthoDB; 431748at2759; -.
DR Proteomes; UP000001055; 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..467
FT /note="Probable cysteine protease ATG4"
FT /id="PRO_0000317841"
FT REGION 32..93
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 343..390
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 429..467
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 47..61
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 62..83
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 343..370
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 440..455
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT ACT_SITE 149
FT /note="Nucleophile"
FT /evidence="ECO:0000250|UniProtKB:Q9Y4P1"
FT ACT_SITE 325
FT /evidence="ECO:0000250|UniProtKB:Q9Y4P1"
FT ACT_SITE 327
FT /evidence="ECO:0000250|UniProtKB:Q9Y4P1"
SQ SEQUENCE 467 AA; 51812 MW; ABC560138654EC3A CRC64;
MNDFERFGRN VVRTFYDPPP CNESNEPIWL LGQRYDSRPP LPKPAPSDSS TTATATAQAE
RNEDESWIRT SIDDKERKEA PNGEDPTQYG NWPSAFLDDF ESRVWMTYRS GFSPIQKSQD
PKATSAMSFR VRMQNLASPG FTSDAGFGCM IRSGQCILAN ALQILRLGRD WRWQENHADK
DHAEILSLFA DDPQAPFSIH RFVEHGAAVC GKYPGEWFGP SAAARCIQDL ANKHREAGLK
VYVSGDGADV YEDKLKQVAV DEDGLWQPTL ILVGTRLGID KITPVYWEAL KASLQIPQSI
GIAGGRPSAS HYFVGVQGNN FYYLDPHSTR PLLPFHPPSL AAATSDTPNL TASTTSVSST
TSSTTIVPPA DSIPAPSDPR QSLYPPSDLS TCHTRRIRRL QIREMDPSML LAFLVTSEAD
YQDWKEGVQG VQGKSVVHVQ DKEPPPRGQE REGAIDEVES WDEDGLQ
