ATG4_EMENI
ID ATG4_EMENI Reviewed; 402 AA.
AC Q5B7L0; C8VH95;
DT 19-JUL-2005, integrated into UniProtKB/Swiss-Prot.
DT 16-NOV-2011, sequence version 2.
DT 03-AUG-2022, entry version 92.
DE RecName: Full=Cysteine protease atg4;
DE EC=3.4.22.-;
DE AltName: Full=Autophagy-related protein 4;
GN Name=atg4; ORFNames=AN3470;
OS Emericella nidulans (strain FGSC A4 / ATCC 38163 / CBS 112.46 / NRRL 194 /
OS M139) (Aspergillus nidulans).
OC Eukaryota; Fungi; Dikarya; Ascomycota; Pezizomycotina; Eurotiomycetes;
OC Eurotiomycetidae; Eurotiales; Aspergillaceae; Aspergillus;
OC Aspergillus subgen. Nidulantes.
OX NCBI_TaxID=227321;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=FGSC A4 / ATCC 38163 / CBS 112.46 / NRRL 194 / M139;
RX PubMed=16372000; DOI=10.1038/nature04341;
RA Galagan J.E., Calvo S.E., Cuomo C., Ma L.-J., Wortman J.R., Batzoglou S.,
RA Lee S.-I., Bastuerkmen M., Spevak C.C., Clutterbuck J., Kapitonov V.,
RA Jurka J., Scazzocchio C., Farman M.L., Butler J., Purcell S., Harris S.,
RA Braus G.H., Draht O., Busch S., D'Enfert C., Bouchier C., Goldman G.H.,
RA Bell-Pedersen D., Griffiths-Jones S., Doonan J.H., Yu J., Vienken K.,
RA Pain A., Freitag M., Selker E.U., Archer D.B., Penalva M.A., Oakley B.R.,
RA Momany M., Tanaka T., Kumagai T., Asai K., Machida M., Nierman W.C.,
RA Denning D.W., Caddick M.X., Hynes M., Paoletti M., Fischer R., Miller B.L.,
RA Dyer P.S., Sachs M.S., Osmani S.A., Birren B.W.;
RT "Sequencing of Aspergillus nidulans and comparative analysis with A.
RT fumigatus and A. oryzae.";
RL Nature 438:1105-1115(2005).
RN [2]
RP GENOME REANNOTATION.
RC STRAIN=FGSC A4 / ATCC 38163 / CBS 112.46 / NRRL 194 / M139;
RX PubMed=19146970; DOI=10.1016/j.fgb.2008.12.003;
RA Wortman J.R., Gilsenan J.M., Joardar V., Deegan J., Clutterbuck J.,
RA Andersen M.R., Archer D., Bencina M., Braus G., Coutinho P., von Dohren H.,
RA Doonan J., Driessen A.J., Durek P., Espeso E., Fekete E., Flipphi M.,
RA Estrada C.G., Geysens S., Goldman G., de Groot P.W., Hansen K.,
RA Harris S.D., Heinekamp T., Helmstaedt K., Henrissat B., Hofmann G.,
RA Homan T., Horio T., Horiuchi H., James S., Jones M., Karaffa L.,
RA Karanyi Z., Kato M., Keller N., Kelly D.E., Kiel J.A., Kim J.M.,
RA van der Klei I.J., Klis F.M., Kovalchuk A., Krasevec N., Kubicek C.P.,
RA Liu B., Maccabe A., Meyer V., Mirabito P., Miskei M., Mos M., Mullins J.,
RA Nelson D.R., Nielsen J., Oakley B.R., Osmani S.A., Pakula T., Paszewski A.,
RA Paulsen I., Pilsyk S., Pocsi I., Punt P.J., Ram A.F., Ren Q., Robellet X.,
RA Robson G., Seiboth B., van Solingen P., Specht T., Sun J.,
RA Taheri-Talesh N., Takeshita N., Ussery D., vanKuyk P.A., Visser H.,
RA van de Vondervoort P.J., de Vries R.P., Walton J., Xiang X., Xiong Y.,
RA Zeng A.P., Brandt B.W., Cornell M.J., van den Hondel C.A., Visser J.,
RA Oliver S.G., Turner G.;
RT "The 2008 update of the Aspergillus nidulans genome annotation: a community
RT effort.";
RL Fungal Genet. Biol. 46:S2-13(2009).
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=EAA63010.1; Type=Erroneous gene model prediction; Evidence={ECO:0000305};
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DR EMBL; AACD01000058; EAA63010.1; ALT_SEQ; Genomic_DNA.
DR EMBL; BN001306; CBF82642.1; -; Genomic_DNA.
DR RefSeq; XP_661074.1; XM_655982.1.
DR AlphaFoldDB; Q5B7L0; -.
DR SMR; Q5B7L0; -.
DR STRING; 162425.CADANIAP00009563; -.
DR MEROPS; C54.001; -.
DR EnsemblFungi; CBF82642; CBF82642; ANIA_03470.
DR EnsemblFungi; EAA63010; EAA63010; AN3470.2.
DR GeneID; 2874196; -.
DR KEGG; ani:AN3470.2; -.
DR VEuPathDB; FungiDB:AN3470; -.
DR eggNOG; KOG2674; Eukaryota.
DR HOGENOM; CLU_021259_5_1_1; -.
DR InParanoid; Q5B7L0; -.
DR OMA; CHTRRIR; -.
DR OrthoDB; 431748at2759; -.
DR Proteomes; UP000000560; Chromosome VI.
DR Proteomes; UP000005890; Unassembled WGS sequence.
DR GO; GO:0005829; C:cytosol; IEA:EnsemblFungi.
DR GO; GO:0005634; C:nucleus; IEA:UniProtKB-SubCell.
DR GO; GO:0000407; C:phagophore assembly site; IEA:UniProtKB-SubCell.
DR GO; GO:0019786; F:Atg8-specific peptidase activity; IEA:EnsemblFungi.
DR GO; GO:0000045; P:autophagosome assembly; IEA:EnsemblFungi.
DR GO; GO:0000422; P:autophagy of mitochondrion; IEA:EnsemblFungi.
DR GO; GO:0006501; P:C-terminal protein lipidation; IEA:EnsemblFungi.
DR GO; GO:0044805; P:late nucleophagy; IEA:EnsemblFungi.
DR GO; GO:0034727; P:piecemeal microautophagy of the nucleus; IEA:EnsemblFungi.
DR GO; GO:0051697; P:protein delipidation; IEA:EnsemblFungi.
DR GO; GO:0006612; P:protein targeting to membrane; IEA:EnsemblFungi.
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..402
FT /note="Cysteine protease atg4"
FT /id="PRO_0000215862"
FT REGION 46..68
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 54..68
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT ACT_SITE 128
FT /note="Nucleophile"
FT /evidence="ECO:0000250|UniProtKB:Q9Y4P1"
FT ACT_SITE 302
FT /evidence="ECO:0000250|UniProtKB:Q9Y4P1"
FT ACT_SITE 304
FT /evidence="ECO:0000250|UniProtKB:Q9Y4P1"
SQ SEQUENCE 402 AA; 45379 MW; 3318D94C706B9AFA CRC64;
MNATDIERCR KRIIQYIWDP EPKNDEEPGS PIWCLGTRYP PQCVEETADE SRNPDHGQQQ
NTNTSAPGWP EAFLLDFESK IWMTYRSNFP PIPKDAGQEG SLSLTLGVRL RSQLIDAQGF
TSDTGWGCMI RSGQSLLANS MAILLLGRDW RRGERLEEEG KLLSLFADSP HAPFSIHSFV
KHGADFCGKH PGEWFGPTAT ARCIQGLAAR YDQSNLQVYI ADDNSDVHQD KFMSVSRDEK
GTVRPTLILL GLRLGIDRIT AVYWNGLKAV LQLPQSVGIA GGRPSASHYF VAVQGSHFFY
LDPHNTRPAL RYSESGTYTE DEVNTYHTRR LRRLNIQDMD PSMLIGFLIR DEDDWEDWKA
RIMSLEGKPI ITILSESDAA SWKGRREALD EVEAFDDLDV AL
