ATG4_YEAST
ID ATG4_YEAST Reviewed; 494 AA.
AC P53867; D6W0W7;
DT 01-OCT-1996, integrated into UniProtKB/Swiss-Prot.
DT 15-MAR-2005, sequence version 2.
DT 03-AUG-2022, entry version 174.
DE RecName: Full=Cysteine protease ATG4 {ECO:0000305};
DE EC=3.4.22.- {ECO:0000269|PubMed:11038174, ECO:0000269|PubMed:11100732, ECO:0000269|PubMed:16680092, ECO:0000269|PubMed:17632063, ECO:0000269|PubMed:18725539};
DE AltName: Full=Autophagy-related protein 4 {ECO:0000303|PubMed:8224160};
GN Name=ATG4 {ECO:0000303|PubMed:22240591, ECO:0000312|SGD:S000005167};
GN Synonyms=APG4 {ECO:0000303|PubMed:8224160},
GN AUT2 {ECO:0000303|PubMed:8050581}; OrderedLocusNames=YNL223W;
GN ORFNames=N1274;
OS Saccharomyces cerevisiae (strain ATCC 204508 / S288c) (Baker's yeast).
OC Eukaryota; Fungi; Dikarya; Ascomycota; Saccharomycotina; Saccharomycetes;
OC Saccharomycetales; Saccharomycetaceae; Saccharomyces.
OX NCBI_TaxID=559292;
RN [1]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RX PubMed=8896273;
RX DOI=10.1002/(sici)1097-0061(199609)12:10b<1071::aid-yea4>3.0.co;2-s;
RA Pandolfo D., de Antoni A., Lanfranchi G., Valle G.;
RT "The DNA sequence of cosmid 14-5 from chromosome XIV reveals 21 open
RT reading frames including a novel gene encoding a globin-like domain.";
RL Yeast 12:1071-1076(1996).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=ATCC 204508 / S288c;
RX PubMed=9169873;
RA Philippsen P., Kleine K., Poehlmann R., Duesterhoeft A., Hamberg K.,
RA Hegemann J.H., Obermaier B., Urrestarazu L.A., Aert R., Albermann K.,
RA Altmann R., Andre B., Baladron V., Ballesta J.P.G., Becam A.-M.,
RA Beinhauer J.D., Boskovic J., Buitrago M.J., Bussereau F., Coster F.,
RA Crouzet M., D'Angelo M., Dal Pero F., De Antoni A., del Rey F., Doignon F.,
RA Domdey H., Dubois E., Fiedler T.A., Fleig U., Floeth M., Fritz C.,
RA Gaillardin C., Garcia-Cantalejo J.M., Glansdorff N., Goffeau A.,
RA Gueldener U., Herbert C.J., Heumann K., Heuss-Neitzel D., Hilbert H.,
RA Hinni K., Iraqui Houssaini I., Jacquet M., Jimenez A., Jonniaux J.-L.,
RA Karpfinger-Hartl L., Lanfranchi G., Lepingle A., Levesque H., Lyck R.,
RA Maftahi M., Mallet L., Maurer C.T.C., Messenguy F., Mewes H.-W., Moestl D.,
RA Nasr F., Nicaud J.-M., Niedenthal R.K., Pandolfo D., Pierard A.,
RA Piravandi E., Planta R.J., Pohl T.M., Purnelle B., Rebischung C.,
RA Remacha M.A., Revuelta J.L., Rinke M., Saiz J.E., Sartorello F.,
RA Scherens B., Sen-Gupta M., Soler-Mira A., Urbanus J.H.M., Valle G.,
RA Van Dyck L., Verhasselt P., Vierendeels F., Vissers S., Voet M.,
RA Volckaert G., Wach A., Wambutt R., Wedler H., Zollner A., Hani J.;
RT "The nucleotide sequence of Saccharomyces cerevisiae chromosome XIV and its
RT evolutionary implications.";
RL Nature 387:93-98(1997).
RN [3]
RP GENOME REANNOTATION.
RC STRAIN=ATCC 204508 / S288c;
RX PubMed=24374639; DOI=10.1534/g3.113.008995;
RA Engel S.R., Dietrich F.S., Fisk D.G., Binkley G., Balakrishnan R.,
RA Costanzo M.C., Dwight S.S., Hitz B.C., Karra K., Nash R.S., Weng S.,
RA Wong E.D., Lloyd P., Skrzypek M.S., Miyasato S.R., Simison M., Cherry J.M.;
RT "The reference genome sequence of Saccharomyces cerevisiae: Then and now.";
RL G3 (Bethesda) 4:389-398(2014).
RN [4]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RA Sun Z., Hampsey M.;
RL Submitted (MAR-1996) to the EMBL/GenBank/DDBJ databases.
RN [5]
RP IDENTIFICATION OF PROBABLE INITIATION SITE.
RX PubMed=12748633; DOI=10.1038/nature01644;
RA Kellis M., Patterson N., Endrizzi M., Birren B.W., Lander E.S.;
RT "Sequencing and comparison of yeast species to identify genes and
RT regulatory elements.";
RL Nature 423:241-254(2003).
RN [6]
RP FUNCTION.
RX PubMed=8224160; DOI=10.1016/0014-5793(93)80398-e;
RA Tsukada M., Ohsumi Y.;
RT "Isolation and characterization of autophagy-defective mutants of
RT Saccharomyces cerevisiae.";
RL FEBS Lett. 333:169-174(1993).
RN [7]
RP FUNCTION.
RX PubMed=8050581; DOI=10.1016/0014-5793(94)00672-5;
RA Thumm M., Egner R., Koch B., Schlumpberger M., Straub M., Veenhuis M.,
RA Wolf D.H.;
RT "Isolation of autophagocytosis mutants of Saccharomyces cerevisiae.";
RL FEBS Lett. 349:275-280(1994).
RN [8]
RP FUNCTION, AND INTERACTION WITH ATG8; TUB1 AND TUB2.
RX PubMed=9649430; DOI=10.1093/emboj/17.13.3597;
RA Lang T., Schaeffeler E., Bernreuther D., Bredschneider M., Wolf D.H.,
RA Thumm M.;
RT "Aut2p and Aut7p, two novel microtubule-associated proteins are essential
RT for delivery of autophagic vesicles to the vacuole.";
RL EMBO J. 17:3597-3607(1998).
RN [9]
RP FUNCTION, ACTIVITY REGULATION, ACTIVE SITE, AND MUTAGENESIS OF CYS-147.
RX PubMed=11038174; DOI=10.1083/jcb.151.2.263;
RA Kirisako T., Ichimura Y., Okada H., Kabeya Y., Mizushima N., Yoshimori T.,
RA Ohsumi M., Takao T., Noda T., Ohsumi Y.;
RT "The reversible modification regulates the membrane-binding state of
RT Apg8/Aut7 essential for autophagy and the cytoplasm to vacuole targeting
RT pathway.";
RL J. Cell Biol. 151:263-276(2000).
RN [10]
RP FUNCTION IN ATG8 CLEAVAGE.
RX PubMed=11100732; DOI=10.1038/35044114;
RA Ichimura Y., Kirisako T., Takao T., Satomi Y., Shimonishi Y., Ishihara N.,
RA Mizushima N., Tanida I., Kominami E., Ohsumi M., Noda T., Ohsumi Y.;
RT "A ubiquitin-like system mediates protein lipidation.";
RL Nature 408:488-492(2000).
RN [11]
RP FUNCTION, AND SUBCELLULAR LOCATION.
RX PubMed=11149920; DOI=10.1083/jcb.152.1.51;
RA Kim J., Huang W.-P., Klionsky D.J.;
RT "Membrane recruitment of Aut7p in the autophagy and cytoplasm to vacuole
RT targeting pathways requires Aut1p, Aut2p, and the autophagy conjugation
RT complex.";
RL J. Cell Biol. 152:51-64(2001).
RN [12]
RP FUNCTION.
RX PubMed=11904149; DOI=10.1016/s0014-5793(02)02297-4;
RA Krampe S., Boles E.;
RT "Starvation-induced degradation of yeast hexose transporter Hxt7p is
RT dependent on endocytosis, autophagy and the terminal sequences of the
RT permease.";
RL FEBS Lett. 513:193-196(2002).
RN [13]
RP NOMENCLATURE.
RX PubMed=14536056; DOI=10.1016/s1534-5807(03)00296-x;
RA Klionsky D.J., Cregg J.M., Dunn W.A. Jr., Emr S.D., Sakai Y.,
RA Sandoval I.V., Sibirny A., Subramani S., Thumm M., Veenhuis M., Ohsumi Y.;
RT "A unified nomenclature for yeast autophagy-related genes.";
RL Dev. Cell 5:539-545(2003).
RN [14]
RP SUBCELLULAR LOCATION [LARGE SCALE ANALYSIS].
RX PubMed=14562095; DOI=10.1038/nature02026;
RA Huh W.-K., Falvo J.V., Gerke L.C., Carroll A.S., Howson R.W.,
RA Weissman J.S., O'Shea E.K.;
RT "Global analysis of protein localization in budding yeast.";
RL Nature 425:686-691(2003).
RN [15]
RP LEVEL OF PROTEIN EXPRESSION [LARGE SCALE ANALYSIS].
RX PubMed=14562106; DOI=10.1038/nature02046;
RA Ghaemmaghami S., Huh W.-K., Bower K., Howson R.W., Belle A., Dephoure N.,
RA O'Shea E.K., Weissman J.S.;
RT "Global analysis of protein expression in yeast.";
RL Nature 425:737-741(2003).
RN [16]
RP FUNCTION IN ATG8 CLEAVAGE, AND INTERACTION WITH ATG8.
RX PubMed=16680092; DOI=10.1038/sj.embor.7400698;
RA Amar N., Lustig G., Ichimura Y., Ohsumi Y., Elazar Z.;
RT "Two newly identified sites in the ubiquitin-like protein Atg8 are
RT essential for autophagy.";
RL EMBO Rep. 7:635-642(2006).
RN [17]
RP FUNCTION IN ATG8 CLEAVAGE.
RX PubMed=17632063; DOI=10.1016/j.cell.2007.05.021;
RA Nakatogawa H., Ichimura Y., Ohsumi Y.;
RT "Atg8, a ubiquitin-like protein required for autophagosome formation,
RT mediates membrane tethering and hemifusion.";
RL Cell 130:165-178(2007).
RN [18]
RP FUNCTION IN ATG8 CLEAVAGE.
RX PubMed=18725539; DOI=10.1083/jcb.200801035;
RA Cao Y., Cheong H., Song H., Klionsky D.J.;
RT "In vivo reconstitution of autophagy in Saccharomyces cerevisiae.";
RL J. Cell Biol. 182:703-713(2008).
RN [19]
RP FUNCTION.
RX PubMed=18701704; DOI=10.1091/mbc.e08-04-0363;
RA Krick R., Muehe Y., Prick T., Bremer S., Schlotterhose P., Eskelinen E.L.,
RA Millen J., Goldfarb D.S., Thumm M.;
RT "Piecemeal microautophagy of the nucleus requires the core macroautophagy
RT genes.";
RL Mol. Biol. Cell 19:4492-4505(2008).
RN [20]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-488, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=18407956; DOI=10.1074/mcp.m700468-mcp200;
RA Albuquerque C.P., Smolka M.B., Payne S.H., Bafna V., Eng J., Zhou H.;
RT "A multidimensional chromatography technology for in-depth phosphoproteome
RT analysis.";
RL Mol. Cell. Proteomics 7:1389-1396(2008).
RN [21]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-488, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=19779198; DOI=10.1126/science.1172867;
RA Holt L.J., Tuch B.B., Villen J., Johnson A.D., Gygi S.P., Morgan D.O.;
RT "Global analysis of Cdk1 substrate phosphorylation sites provides insights
RT into evolution.";
RL Science 325:1682-1686(2009).
RN [22]
RP INDUCTION.
RX PubMed=20647741; DOI=10.4161/auto.6.7.12753;
RA Ecker N., Mor A., Journo D., Abeliovich H.;
RT "Induction of autophagic flux by amino acid deprivation is distinct from
RT nitrogen starvation-induced macroautophagy.";
RL Autophagy 6:879-890(2010).
RN [23]
RP FUNCTION IN ATG8-PE DECONJUGATION, AND CATALYTIC ACTIVITY.
RX PubMed=22240591; DOI=10.4161/auto.8.2.18373;
RA Nakatogawa H., Ishii J., Asai E., Ohsumi Y.;
RT "Atg4 recycles inappropriately lipidated Atg8 to promote autophagosome
RT biogenesis.";
RL Autophagy 8:177-186(2012).
RN [24]
RP FUNCTION IN ATG8-PE DECONJUGATION, AND CATALYTIC ACTIVITY.
RX PubMed=22652539; DOI=10.4161/auto.19652;
RA Yu Z.Q., Ni T., Hong B., Wang H.Y., Jiang F.J., Zou S., Chen Y.,
RA Zheng X.L., Klionsky D.J., Liang Y., Xie Z.;
RT "Dual roles of Atg8-PE deconjugation by Atg4 in autophagy.";
RL Autophagy 8:883-892(2012).
RN [25]
RP DISULFIDE BOND, SUBCELLULAR LOCATION, AND MUTAGENESIS OF CYS-338 AND
RP CYS-394.
RX PubMed=25483965; DOI=10.4161/auto.34396;
RA Perez-Perez M.E., Zaffagnini M., Marchand C.H., Crespo J.L., Lemaire S.D.;
RT "The yeast autophagy protease Atg4 is regulated by thioredoxin.";
RL Autophagy 10:1953-1964(2014).
RN [26]
RP MOTIF, DOMAIN, INTERACTION WITH ATG8, AND MUTAGENESIS OF 343-PHE--LEU-346;
RP 424-TYR--ILE-427 AND 446-PHE--ILE-449.
RX PubMed=28287329; DOI=10.1080/15548627.2017.1287651;
RA Skytte Rasmussen M., Mouilleron S., Kumar Shrestha B., Wirth M., Lee R.,
RA Bowitz Larsen K., Abudu Princely Y., O'Reilly N., Sjottem E., Tooze S.A.,
RA Lamark T., Johansen T.;
RT "ATG4B contains a C-terminal LIR motif important for binding and efficient
RT cleavage of mammalian orthologs of yeast Atg8.";
RL Autophagy 13:834-853(2017).
RN [27]
RP FUNCTION, SUBCELLULAR LOCATION, DOMAIN, AND MUTAGENESIS OF 36-TYR--LEU-39;
RP 102-PHE--ILE-105; 424-TYR--ILE-427 AND 446-PHE--ILE-449.
RX PubMed=28330855; DOI=10.15252/embr.201643146;
RA Abreu S., Kriegenburg F., Gomez-Sanchez R., Mari M., Sanchez-Wandelmer J.,
RA Skytte Rasmussen M., Soares Guimaraes R., Zens B., Schuschnig M.,
RA Hardenberg R., Peter M., Johansen T., Kraft C., Martens S., Reggiori F.;
RT "Conserved Atg8 recognition sites mediate Atg4 association with
RT autophagosomal membranes and Atg8 deconjugation.";
RL EMBO Rep. 18:765-780(2017).
RN [28]
RP PHOSPHORYLATION AT SER-307, FUNCTION, SUBCELLULAR LOCATION, INTERACTION
RP WITH ATG8, AND MUTAGENESIS OF 305-SER--SER-307 AND SER-307.
RX PubMed=28821724; DOI=10.1038/s41467-017-00302-3;
RA Sanchez-Wandelmer J., Kriegenburg F., Rohringer S., Schuschnig M.,
RA Gomez-Sanchez R., Zens B., Abreu S., Hardenberg R., Hollenstein D., Gao J.,
RA Ungermann C., Martens S., Kraft C., Reggiori F.;
RT "Atg4 proteolytic activity can be inhibited by Atg1 phosphorylation.";
RL Nat. Commun. 8:295-295(2017).
RN [29]
RP FUNCTION, AND INTERACTION WITH ATG8.
RX PubMed=28704456; DOI=10.1371/journal.pone.0181047;
RA Hirata E., Ohya Y., Suzuki K.;
RT "Atg4 plays an important role in efficient expansion of autophagic
RT isolation membranes by cleaving lipidated Atg8 in Saccharomyces
RT cerevisiae.";
RL PLoS ONE 12:e0181047-e0181047(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 (PubMed:11038174, PubMed:11100732,
CC PubMed:11149920, PubMed:11904149, PubMed:16680092, PubMed:18701704,
CC PubMed:18725539, PubMed:8050581, PubMed:8224160, PubMed:9649430,
CC PubMed:28330855, PubMed:28821724, PubMed:28704456). 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
CC (PubMed:11038174, PubMed:11100732, PubMed:11149920, PubMed:11904149,
CC PubMed:16680092, PubMed:18701704, PubMed:18725539, PubMed:8050581,
CC PubMed:8224160, PubMed:9649430). The protease activity is required for
CC proteolytic activation of ATG8: cleaves the C-terminal amino acid of
CC ATG8 to reveal a C-terminal glycine (PubMed:11038174, PubMed:11100732,
CC PubMed:11149920, PubMed:11904149, PubMed:16680092, PubMed:18701704,
CC PubMed:18725539, PubMed:8050581, PubMed:8224160, PubMed:9649430). 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
CC (PubMed:11038174, PubMed:11100732, PubMed:11149920, PubMed:11904149,
CC PubMed:16680092, PubMed:18701704, PubMed:18725539, PubMed:8050581,
CC PubMed:8224160, PubMed:9649430). The ATG8-PE conjugate mediates
CC tethering between adjacent membranes and stimulates membrane
CC hemifusion, leading to expansion of the autophagosomal membrane during
CC autophagy (PubMed:17632063). 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 (PubMed:22240591, PubMed:22652539, PubMed:28330855,
CC PubMed:28821724, PubMed:28704456). ATG8 delipidation by ATG4 also
CC recycles ATG8-PE generated on inappropriate membranes to maintain a
CC reservoir of unlipidated ATG8 that is required for autophagosome
CC formation at the PAS (PubMed:22240591, PubMed:22652539).
CC {ECO:0000269|PubMed:11038174, ECO:0000269|PubMed:11100732,
CC ECO:0000269|PubMed:11149920, ECO:0000269|PubMed:11904149,
CC ECO:0000269|PubMed:16680092, ECO:0000269|PubMed:17632063,
CC ECO:0000269|PubMed:18701704, ECO:0000269|PubMed:18725539,
CC ECO:0000269|PubMed:22240591, ECO:0000269|PubMed:22652539,
CC ECO:0000269|PubMed:28330855, ECO:0000269|PubMed:28704456,
CC ECO:0000269|PubMed:28821724, ECO:0000269|PubMed:8050581,
CC ECO:0000269|PubMed:8224160, ECO:0000269|PubMed:9649430}.
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:0000269|PubMed:22240591,
CC ECO:0000269|PubMed:22652539};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:67549;
CC Evidence={ECO:0000269|PubMed:22240591, ECO:0000269|PubMed:22652539};
CC -!- ACTIVITY REGULATION: Inhibited by N-ethylmaleimide.
CC {ECO:0000269|PubMed:11038174}.
CC -!- SUBUNIT: Interacts with ATG8 (PubMed:16680092, PubMed:9649430,
CC PubMed:28287329, PubMed:28330855, PubMed:28821724). Interacts with TUB1
CC and TUB2 (PubMed:9649430). {ECO:0000269|PubMed:16680092,
CC ECO:0000269|PubMed:28287329, ECO:0000269|PubMed:28330855,
CC ECO:0000269|PubMed:28821724, ECO:0000269|PubMed:9649430}.
CC -!- INTERACTION:
CC P53867; P38182: ATG8; NbExp=3; IntAct=EBI-29160, EBI-2684;
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000269|PubMed:11149920}. Nucleus
CC {ECO:0000269|PubMed:14562095}. Preautophagosomal structure
CC {ECO:0000269|PubMed:25483965, ECO:0000269|PubMed:28330855,
CC ECO:0000269|PubMed:28821724}.
CC -!- INDUCTION: Expression is induced upon starvation, through the action of
CC transcription factors GCN2 and GCN4. {ECO:0000269|PubMed:20647741}.
CC -!- DOMAIN: The APEAR motif (ATG8-PE association region) plays a key role
CC in ATG4 recruitment to autophagosomal membranes and ATG8 deconjugation
CC (PubMed:28330855). The LIR (LC3-interacting region act cooperatively)
CC and APEAR motifs for the interaction with ATG8 (PubMed:28287329,
CC PubMed:28330855). {ECO:0000269|PubMed:28287329,
CC ECO:0000269|PubMed:28330855}.
CC -!- PTM: Phosphorylation at Ser-307 by ATG1 inhibits autophagy: it takes
CC place on autophagosome membranes and decreases its interaction with
CC ATG8, thereby impairing deconjugation of PE-conjugated forms of ATG8.
CC {ECO:0000269|PubMed:28821724}.
CC -!- PTM: Formation of a disulfide bond between Cys-338 and Cys-394 leads to
CC reduced autophagy (PubMed:25483965). The disulfide bond is reduced by
CC thioredoxin (PubMed:25483965). {ECO:0000269|PubMed:25483965}.
CC -!- MISCELLANEOUS: Present with 3300 molecules/cell in log phase SD medium.
CC {ECO:0000269|PubMed:14562106}.
CC -!- SIMILARITY: Belongs to the peptidase C54 family. {ECO:0000305}.
CC -!- SEQUENCE CAUTION:
CC Sequence=CAA93375.1; Type=Erroneous initiation; Note=Extended N-terminus.; Evidence={ECO:0000305};
CC Sequence=CAA96126.1; Type=Erroneous initiation; Note=Extended N-terminus.; Evidence={ECO:0000305};
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DR EMBL; Z69381; CAA93375.1; ALT_INIT; Genomic_DNA.
DR EMBL; Z71499; CAA96126.1; ALT_INIT; Genomic_DNA.
DR EMBL; U20390; AAA86498.1; -; Genomic_DNA.
DR EMBL; BK006947; DAA10333.1; -; Genomic_DNA.
DR PIR; S63181; S63181.
DR RefSeq; NP_014176.2; NM_001183061.1.
DR AlphaFoldDB; P53867; -.
DR SMR; P53867; -.
DR BioGRID; 35613; 88.
DR DIP; DIP-2339N; -.
DR IntAct; P53867; 5.
DR STRING; 4932.YNL223W; -.
DR MEROPS; C54.001; -.
DR iPTMnet; P53867; -.
DR PaxDb; P53867; -.
DR PRIDE; P53867; -.
DR EnsemblFungi; YNL223W_mRNA; YNL223W; YNL223W.
DR GeneID; 855498; -.
DR KEGG; sce:YNL223W; -.
DR SGD; S000005167; ATG4.
DR VEuPathDB; FungiDB:YNL223W; -.
DR eggNOG; KOG2674; Eukaryota.
DR GeneTree; ENSGT00530000063000; -.
DR HOGENOM; CLU_021259_5_3_1; -.
DR InParanoid; P53867; -.
DR OMA; NREHHEA; -.
DR BioCyc; YEAST:G3O-33226-MON; -.
DR PRO; PR:P53867; -.
DR Proteomes; UP000002311; Chromosome XIV.
DR RNAct; P53867; protein.
DR GO; GO:0005737; C:cytoplasm; IDA:UniProtKB.
DR GO; GO:0005829; C:cytosol; IDA:UniProtKB.
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; IDA:SGD.
DR GO; GO:0000045; P:autophagosome assembly; IMP:UniProtKB.
DR GO; GO:0006914; P:autophagy; IMP:UniProtKB.
DR GO; GO:0000422; P:autophagy of mitochondrion; IMP:SGD.
DR GO; GO:0006501; P:C-terminal protein lipidation; IMP:SGD.
DR GO; GO:0032258; P:cytoplasm to vacuole transport by the Cvt pathway; IMP:SGD.
DR GO; GO:0044805; P:late nucleophagy; IMP:SGD.
DR GO; GO:0034727; P:piecemeal microautophagy of the nucleus; IMP:SGD.
DR GO; GO:0051697; P:protein delipidation; IDA:SGD.
DR GO; GO:0006612; P:protein targeting to membrane; IMP:UniProtKB.
DR GO; GO:0006508; P:proteolysis; IMP:UniProtKB.
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; Disulfide bond; Hydrolase; Isopeptide bond; Nucleus;
KW Phosphoprotein; Protease; Protein transport; Reference proteome;
KW Thiol protease; Transport; Ubl conjugation pathway.
FT CHAIN 1..494
FT /note="Cysteine protease ATG4"
FT /id="PRO_0000215870"
FT MOTIF 102..105
FT /note="APEAR"
FT /evidence="ECO:0000269|PubMed:28330855"
FT MOTIF 424..427
FT /note="LIR"
FT /evidence="ECO:0000269|PubMed:28287329,
FT ECO:0000269|PubMed:28330855"
FT ACT_SITE 147
FT /note="Nucleophile"
FT /evidence="ECO:0000305|PubMed:11038174"
FT ACT_SITE 322
FT /evidence="ECO:0000250|UniProtKB:Q9Y4P1"
FT ACT_SITE 324
FT /evidence="ECO:0000250|UniProtKB:Q9Y4P1"
FT MOD_RES 307
FT /note="Phosphoserine; by ATG1"
FT /evidence="ECO:0000269|PubMed:28821724"
FT MOD_RES 488
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:18407956,
FT ECO:0007744|PubMed:19779198"
FT DISULFID 338..394
FT /evidence="ECO:0000269|PubMed:25483965"
FT MUTAGEN 36..39
FT /note="YIVL->AIVA: Impaired autophagy."
FT /evidence="ECO:0000269|PubMed:28330855"
FT MUTAGEN 102..105
FT /note="FVPI->AVPA: Impaired autophagy caused by decreased
FT delipdation of ATG8. Reduced recruitment to
FT preautophagosomal structures."
FT /evidence="ECO:0000269|PubMed:28330855"
FT MUTAGEN 147
FT /note="C->S,A: Abolishes the proteolytic activity and
FT decreases autophagy."
FT /evidence="ECO:0000269|PubMed:11038174"
FT MUTAGEN 305..307
FT /note="SSS->AAA: Abolished phosphorylation by ATG1."
FT /evidence="ECO:0000269|PubMed:28821724"
FT MUTAGEN 307
FT /note="S->A: Abolished phosphorylation by ATG1, leading to
FT increased interaction with ATG8."
FT /evidence="ECO:0000269|PubMed:28821724"
FT MUTAGEN 307
FT /note="S->D: Phospho-mimetic mutant; decreased integration
FT with ATG8, leading to impaired decreased delipdation of
FT ATG8."
FT /evidence="ECO:0000269|PubMed:28821724"
FT MUTAGEN 338
FT /note="C->S: Increased recruitmentto the phagophore
FT assembly site."
FT /evidence="ECO:0000269|PubMed:25483965"
FT MUTAGEN 343..346
FT /note="FGKL->AGKA: Does not affect interaction with ATG8."
FT /evidence="ECO:0000269|PubMed:28287329"
FT MUTAGEN 394
FT /note="C->S: Increased recruitmentto the phagophore
FT assembly site."
FT /evidence="ECO:0000269|PubMed:25483965"
FT MUTAGEN 424..427
FT /note="YVDI->AVDA: Decreased autophagy caused by strongly
FT reduced interaction with ATG8."
FT /evidence="ECO:0000269|PubMed:28287329,
FT ECO:0000269|PubMed:28330855"
FT MUTAGEN 446..449
FT /note="FQDI->AQDA: Does not affect autophagy. Slightly
FT decreased interaction with ATG8."
FT /evidence="ECO:0000269|PubMed:28287329,
FT ECO:0000269|PubMed:28330855"
SQ SEQUENCE 494 AA; 55143 MW; E68ABCA662A28C32 CRC64;
MQRWLQLWKM DLVQKVSHGV FEGSSEEPAA LMNHDYIVLG EVYPERDEES GAEQCEQDCR
YRGEAVSDGF LSSLFGREIS SYTKEFLLDV QSRVNFTYRT RFVPIARAPD GPSPLSLNLL
VRTNPISTIE DYIANPDCFN TDIGWGCMIR TGQSLLGNAL QILHLGRDFR VNGNESLERE
SKFVNWFNDT PEAPFSLHNF VSAGTELSDK RPGEWFGPAA TARSIQSLIY GFPECGIDDC
IVSVSSGDIY ENEVEKVFAE NPNSRILFLL GVKLGINAVN ESYRESICGI LSSTQSVGIA
GGRPSSSLYF FGYQGNEFLH FDPHIPQPAV EDSFVESCHT SKFGKLQLSE MDPSMLIGIL
IKGEKDWQQW KLEVAESAII NVLAKRMDDF DVSCSMDDVE SVSSNSMKKD ASNNENLGVL
EGDYVDIGAI FPHTTNTEDV DEYDCFQDIH CKKQKIVVMG NTHTVNANLT DYEVEGVLVE
KETVGIHSPI DEKC
