ATG4_GIBZE
ID ATG4_GIBZE Reviewed; 469 AA.
AC A0A098DRK7; A0A0E0SDH2; A0A1C3YLC4;
DT 25-APR-2018, integrated into UniProtKB/Swiss-Prot.
DT 07-JAN-2015, sequence version 1.
DT 03-AUG-2022, entry version 39.
DE RecName: Full=Cysteine protease ATG4 {ECO:0000250|UniProtKB:P53867};
DE EC=3.4.22.- {ECO:0000250|UniProtKB:P53867};
DE AltName: Full=Autophagy-related protein 4 {ECO:0000303|PubMed:28894236};
GN Name=ATG4 {ECO:0000303|PubMed:28894236}; ORFNames=FGRAMPH1_01T26115;
OS Gibberella zeae (strain ATCC MYA-4620 / CBS 123657 / FGSC 9075 / NRRL 31084
OS / PH-1) (Wheat head blight fungus) (Fusarium graminearum).
OC Eukaryota; Fungi; Dikarya; Ascomycota; Pezizomycotina; Sordariomycetes;
OC Hypocreomycetidae; Hypocreales; Nectriaceae; Fusarium.
OX NCBI_TaxID=229533;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=ATCC MYA-4620 / CBS 123657 / FGSC 9075 / NRRL 31084 / PH-1;
RX PubMed=17823352; DOI=10.1126/science.1143708;
RA Cuomo C.A., Gueldener U., Xu J.-R., Trail F., Turgeon B.G., Di Pietro A.,
RA Walton J.D., Ma L.-J., Baker S.E., Rep M., Adam G., Antoniw J., Baldwin T.,
RA Calvo S.E., Chang Y.-L., DeCaprio D., Gale L.R., Gnerre S., Goswami R.S.,
RA Hammond-Kosack K., Harris L.J., Hilburn K., Kennell J.C., Kroken S.,
RA Magnuson J.K., Mannhaupt G., Mauceli E.W., Mewes H.-W., Mitterbauer R.,
RA Muehlbauer G., Muensterkoetter M., Nelson D., O'Donnell K., Ouellet T.,
RA Qi W., Quesneville H., Roncero M.I.G., Seong K.-Y., Tetko I.V., Urban M.,
RA Waalwijk C., Ward T.J., Yao J., Birren B.W., Kistler H.C.;
RT "The Fusarium graminearum genome reveals a link between localized
RT polymorphism and pathogen specialization.";
RL Science 317:1400-1402(2007).
RN [2]
RP GENOME REANNOTATION.
RC STRAIN=ATCC MYA-4620 / CBS 123657 / FGSC 9075 / NRRL 31084 / PH-1;
RX PubMed=20237561; DOI=10.1038/nature08850;
RA Ma L.-J., van der Does H.C., Borkovich K.A., Coleman J.J., Daboussi M.-J.,
RA Di Pietro A., Dufresne M., Freitag M., Grabherr M., Henrissat B.,
RA Houterman P.M., Kang S., Shim W.-B., Woloshuk C., Xie X., Xu J.-R.,
RA Antoniw J., Baker S.E., Bluhm B.H., Breakspear A., Brown D.W.,
RA Butchko R.A.E., Chapman S., Coulson R., Coutinho P.M., Danchin E.G.J.,
RA Diener A., Gale L.R., Gardiner D.M., Goff S., Hammond-Kosack K.E.,
RA Hilburn K., Hua-Van A., Jonkers W., Kazan K., Kodira C.D., Koehrsen M.,
RA Kumar L., Lee Y.-H., Li L., Manners J.M., Miranda-Saavedra D.,
RA Mukherjee M., Park G., Park J., Park S.-Y., Proctor R.H., Regev A.,
RA Ruiz-Roldan M.C., Sain D., Sakthikumar S., Sykes S., Schwartz D.C.,
RA Turgeon B.G., Wapinski I., Yoder O., Young S., Zeng Q., Zhou S.,
RA Galagan J., Cuomo C.A., Kistler H.C., Rep M.;
RT "Comparative genomics reveals mobile pathogenicity chromosomes in
RT Fusarium.";
RL Nature 464:367-373(2010).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=ATCC MYA-4620 / CBS 123657 / FGSC 9075 / NRRL 31084 / PH-1;
RX PubMed=26198851; DOI=10.1186/s12864-015-1756-1;
RA King R., Urban M., Hammond-Kosack M.C.U., Hassani-Pak K.,
RA Hammond-Kosack K.E.;
RT "The completed genome sequence of the pathogenic ascomycete fungus Fusarium
RT graminearum.";
RL BMC Genomics 16:544-544(2015).
RN [4]
RP IDENTIFICATION, FUNCTION, AND DISRUPTION PHENOTYPE.
RX PubMed=28894236; DOI=10.1038/s41598-017-11640-z;
RA Lv W., Wang C., Yang N., Que Y., Talbot N.J., Wang Z.;
RT "Genome-wide functional analysis reveals that autophagy is necessary for
RT growth, sporulation, deoxynivalenol production and virulence in Fusarium
RT graminearum.";
RL Sci. Rep. 7:11062-11062(2017).
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 (By similarity). Autophagy is required for proper vegetative
CC growth, asexual/sexual reproduction, and full virulence
CC (PubMed:28894236). Autophagy is particularly involved in the
CC biosynthesis of deoxynivalenol (DON), an important virulence
CC determinant (PubMed:28894236). {ECO:0000250|UniProtKB:P53867,
CC ECO:0000269|PubMed:28894236}.
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 (By similarity).
CC {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 -!- DISRUPTION PHENOTYPE: Significantly decreases the radial growth of
CC colonies under nutrient-rich conditions (PubMed:28894236). Reduces
CC strongly the production of deoxynivalenol (DON), an important virulence
CC determinant (PubMed:28894236). {ECO:0000269|PubMed:28894236}.
CC -!- SIMILARITY: Belongs to the peptidase C54 family. {ECO:0000305}.
CC -!- SEQUENCE CAUTION:
CC Sequence=SCB65352.1; 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; HG970335; SCB65352.1; ALT_SEQ; Genomic_DNA.
DR AlphaFoldDB; A0A098DRK7; -.
DR SMR; A0A098DRK7; -.
DR STRING; 229533.A0A098DRK7; -.
DR Proteomes; UP000070720; 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 3: Inferred from homology;
KW Autophagy; Cytoplasm; Hydrolase; Nucleus; Protease; Protein transport;
KW Reference proteome; Thiol protease; Transport.
FT CHAIN 1..469
FT /note="Cysteine protease ATG4"
FT /id="PRO_0000443873"
FT REGION 48..99
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 443..469
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT ACT_SITE 172
FT /note="Nucleophile"
FT /evidence="ECO:0000250|UniProtKB:Q9Y4P1"
FT ACT_SITE 362
FT /evidence="ECO:0000250|UniProtKB:Q9Y4P1"
FT ACT_SITE 364
FT /evidence="ECO:0000250|UniProtKB:Q9Y4P1"
SQ SEQUENCE 469 AA; 52489 MW; 6AC758D5F56FAA72 CRC64;
MERAMANVDL GPYRRIVQIF WDPEPTNDVV HDQPVWCLGR SYRLNGKKNI KADDHHPQTP
PSVLKAETET QEAHDTAQPP NPPTNAPDTP PDSISSSFSS SLAYDDPVVD GGWPSGFISD
FESKIWMTYR SEFEPIPRST NPQATSALSL SMRLKSQLGD QSPFSSDSGW GCMIRSGQSM
LANTIAMVRL GRGDWRRGES VEEECRLLKD FADDPRAPYS IHSFVRHGAS ACGKYPGEWF
GPSATARCIQ ALTNSHESSI RVYSTGDGPD VYEDEFMQIA KPPGEDFHPT LVLVGTRLGI
DKITPVYWEA LIAALQMPQS ESQGKYYQYI TRTFSALTIR SGRPSSSHYF IGAQGSFLFY
LDPHHTRVAL PYHEDPIEYT SEEIASCHTP RLRRIHVREM DPSMLIGFLI QNEVDWQELK
RNVKHVQGKS IIHITDRNAV LGGSSEGRES AIDEVETLSD DDTDTIHEA
