ATG4_MAGO7
ID ATG4_MAGO7 Reviewed; 491 AA.
AC Q523C3; A4QRH7; G4N7F2;
DT 19-JUL-2005, integrated into UniProtKB/Swiss-Prot.
DT 12-JUN-2007, sequence version 2.
DT 03-AUG-2022, entry version 81.
DE RecName: Full=Cysteine protease ATG4;
DE EC=3.4.22.-;
DE AltName: Full=Autophagy-related protein 4;
GN Name=ATG4; ORFNames=MGG_03580;
OS Magnaporthe oryzae (strain 70-15 / ATCC MYA-4617 / FGSC 8958) (Rice blast
OS fungus) (Pyricularia oryzae).
OC Eukaryota; Fungi; Dikarya; Ascomycota; Pezizomycotina; Sordariomycetes;
OC Sordariomycetidae; Magnaporthales; Pyriculariaceae; Pyricularia.
OX NCBI_TaxID=242507;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=70-15 / ATCC MYA-4617 / FGSC 8958;
RX PubMed=15846337; DOI=10.1038/nature03449;
RA Dean R.A., Talbot N.J., Ebbole D.J., Farman M.L., Mitchell T.K.,
RA Orbach M.J., Thon M.R., Kulkarni R., Xu J.-R., Pan H., Read N.D.,
RA Lee Y.-H., Carbone I., Brown D., Oh Y.Y., Donofrio N., Jeong J.S.,
RA Soanes D.M., Djonovic S., Kolomiets E., Rehmeyer C., Li W., Harding M.,
RA Kim S., Lebrun M.-H., Bohnert H., Coughlan S., Butler J., Calvo S.E.,
RA Ma L.-J., Nicol R., Purcell S., Nusbaum C., Galagan J.E., Birren B.W.;
RT "The genome sequence of the rice blast fungus Magnaporthe grisea.";
RL Nature 434:980-986(2005).
RN [2]
RP FUNCTION, INTERACTION WITH ATG8, MUTAGENESIS OF CYS-206, INDUCTION, AND
RP SUBCELLULAR LOCATION.
RX PubMed=19923912; DOI=10.4161/auto.6.1.10438;
RA Liu T.B., Liu X.H., Lu J.P., Zhang L., Min H., Lin F.C.;
RT "The cysteine protease MoAtg4 interacts with MoAtg8 and is required for
RT differentiation and pathogenesis in Magnaporthe oryzae.";
RL Autophagy 6:74-85(2010).
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:19923912). 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:19923912}.
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 -!- SUBUNIT: Interacts with ATG8. {ECO:0000269|PubMed:19923912}.
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000269|PubMed:19923912}. Nucleus
CC {ECO:0000250|UniProtKB:P53867}. Preautophagosomal structure
CC {ECO:0000250|UniProtKB:P53867}.
CC -!- INDUCTION: Expressed throughout growth and development.
CC {ECO:0000269|PubMed:19923912}.
CC -!- SIMILARITY: Belongs to the peptidase C54 family. {ECO:0000305}.
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DR EMBL; CM001234; EHA50011.1; -; Genomic_DNA.
DR RefSeq; XP_003716330.1; XM_003716282.1.
DR AlphaFoldDB; Q523C3; -.
DR SMR; Q523C3; -.
DR STRING; 318829.MGG_03580T0; -.
DR MEROPS; C54.001; -.
DR EnsemblFungi; MGG_03580T0; MGG_03580T0; MGG_03580.
DR GeneID; 2676731; -.
DR KEGG; mgr:MGG_03580; -.
DR VEuPathDB; FungiDB:MGG_03580; -.
DR eggNOG; KOG2674; Eukaryota.
DR HOGENOM; CLU_021259_5_1_1; -.
DR InParanoid; Q523C3; -.
DR OMA; CHTRRIR; -.
DR OrthoDB; 431748at2759; -.
DR PHI-base; PHI:2072; -.
DR Proteomes; UP000009058; Chromosome 4.
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 1: Evidence at protein level;
KW Autophagy; Cytoplasm; Hydrolase; Nucleus; Protease; Protein transport;
KW Reference proteome; Thiol protease; Transport; Ubl conjugation pathway.
FT CHAIN 1..491
FT /note="Cysteine protease ATG4"
FT /id="PRO_0000215864"
FT REGION 53..137
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 457..491
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 53..106
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 116..134
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT ACT_SITE 206
FT /note="Nucleophile"
FT /evidence="ECO:0000250|UniProtKB:P53867"
FT ACT_SITE 385
FT /evidence="ECO:0000250|UniProtKB:Q9Y4P1"
FT ACT_SITE 387
FT /evidence="ECO:0000250|UniProtKB:Q9Y4P1"
FT MUTAGEN 206
FT /note="C->A: Abolishes the proteolytic activity and
FT decreases autophagy."
FT /evidence="ECO:0000269|PubMed:19923912"
SQ SEQUENCE 491 AA; 53934 MW; ED2210E6BB5CA632 CRC64;
MDSAVAGAAD IGRYGRRIVR MIWDPEPTND PIANRPAWCL GYEYTLETNI TSKTKGEDSK
LSTATSSDQQ RPPAQANKVP QMPSAQLPTE AAATALSGNT TPPTPEAALE PTKITSQPAA
IDTPPDSVDS SFDSSMAYDD VPDDGGWPPA FLNDFESRIW MTYRSGFEPI PRSTDPTASS
RMSFAMRLKT MADQQAGFTT DSGWGCMIRT GQSLLANSLL TCRLGRSWRR GQAPDEERKL
LSLFADDPRA PYSIHNFVAH GAAKCGKYPG EWFGPSATAR CIHALANATE NSFRVYSTGD
LPDVYEDSFM EVAKPDGKTF HPTLILISTR LGIDKINQVY WESLTATLQL PQSVGIAGGR
PSSSHYFVGA QRSDEDQGSY LFYLDPHHTR PALPFHEDPQ LYTPSDVDSC HTRRLRRLHI
REMDPSMLIG FLILDEENWH AWKSSVKHVQ GKSIITVSEH DPSKGSASGR PSAIDEVETL
SDDDGDTVLD G
