ATG4_SCHPO
ID ATG4_SCHPO Reviewed; 320 AA.
AC Q9P373;
DT 26-APR-2005, integrated into UniProtKB/Swiss-Prot.
DT 01-OCT-2000, sequence version 1.
DT 03-AUG-2022, entry version 114.
DE RecName: Full=Probable cysteine protease atg4;
DE EC=3.4.22.-;
DE AltName: Full=Autophagy-related protein 4;
GN Name=atg4; ORFNames=SPAC19B12.08;
OS Schizosaccharomyces pombe (strain 972 / ATCC 24843) (Fission yeast).
OC Eukaryota; Fungi; Dikarya; Ascomycota; Taphrinomycotina;
OC Schizosaccharomycetes; Schizosaccharomycetales; Schizosaccharomycetaceae;
OC Schizosaccharomyces.
OX NCBI_TaxID=284812;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=972 / ATCC 24843;
RX PubMed=11859360; DOI=10.1038/nature724;
RA Wood V., Gwilliam R., Rajandream M.A., Lyne M.H., Lyne R., Stewart A.,
RA Sgouros J.G., Peat N., Hayles J., Baker S.G., Basham D., Bowman S.,
RA Brooks K., Brown D., Brown S., Chillingworth T., Churcher C.M., Collins M.,
RA Connor R., Cronin A., Davis P., Feltwell T., Fraser A., Gentles S.,
RA Goble A., Hamlin N., Harris D.E., Hidalgo J., Hodgson G., Holroyd S.,
RA Hornsby T., Howarth S., Huckle E.J., Hunt S., Jagels K., James K.D.,
RA Jones L., Jones M., Leather S., McDonald S., McLean J., Mooney P.,
RA Moule S., Mungall K.L., Murphy L.D., Niblett D., Odell C., Oliver K.,
RA O'Neil S., Pearson D., Quail M.A., Rabbinowitsch E., Rutherford K.M.,
RA Rutter S., Saunders D., Seeger K., Sharp S., Skelton J., Simmonds M.N.,
RA Squares R., Squares S., Stevens K., Taylor K., Taylor R.G., Tivey A.,
RA Walsh S.V., Warren T., Whitehead S., Woodward J.R., Volckaert G., Aert R.,
RA Robben J., Grymonprez B., Weltjens I., Vanstreels E., Rieger M.,
RA Schaefer M., Mueller-Auer S., Gabel C., Fuchs M., Duesterhoeft A.,
RA Fritzc C., Holzer E., Moestl D., Hilbert H., Borzym K., Langer I., Beck A.,
RA Lehrach H., Reinhardt R., Pohl T.M., Eger P., Zimmermann W., Wedler H.,
RA Wambutt R., Purnelle B., Goffeau A., Cadieu E., Dreano S., Gloux S.,
RA Lelaure V., Mottier S., Galibert F., Aves S.J., Xiang Z., Hunt C.,
RA Moore K., Hurst S.M., Lucas M., Rochet M., Gaillardin C., Tallada V.A.,
RA Garzon A., Thode G., Daga R.R., Cruzado L., Jimenez J., Sanchez M.,
RA del Rey F., Benito J., Dominguez A., Revuelta J.L., Moreno S.,
RA Armstrong J., Forsburg S.L., Cerutti L., Lowe T., McCombie W.R.,
RA Paulsen I., Potashkin J., Shpakovski G.V., Ussery D., Barrell B.G.,
RA Nurse P.;
RT "The genome sequence of Schizosaccharomyces pombe.";
RL Nature 415:871-880(2002).
RN [2]
RP SUBCELLULAR LOCATION [LARGE SCALE ANALYSIS].
RX PubMed=16823372; DOI=10.1038/nbt1222;
RA Matsuyama A., Arai R., Yashiroda Y., Shirai A., Kamata A., Sekido S.,
RA Kobayashi Y., Hashimoto A., Hamamoto M., Hiraoka Y., Horinouchi S.,
RA Yoshida M.;
RT "ORFeome cloning and global analysis of protein localization in the fission
RT yeast Schizosaccharomyces pombe.";
RL Nat. Biotechnol. 24:841-847(2006).
RN [3]
RP FUNCTION.
RX PubMed=19778961; DOI=10.1099/mic.0.034389-0;
RA Mukaiyama H., Kajiwara S., Hosomi A., Giga-Hama Y., Tanaka N., Nakamura T.,
RA Takegawa K.;
RT "Autophagy-deficient Schizosaccharomyces pombe mutants undergo partial
RT sporulation during nitrogen starvation.";
RL Microbiology 155:3816-3826(2009).
RN [4]
RP FUNCTION, AND DISRUPTION PHENOTYPE.
RX PubMed=23950735; DOI=10.1371/journal.pgen.1003715;
RA Sun L.L., Li M., Suo F., Liu X.M., Shen E.Z., Yang B., Dong M.Q., He W.Z.,
RA Du L.L.;
RT "Global analysis of fission yeast mating genes reveals new autophagy
RT factors.";
RL PLoS Genet. 9:E1003715-E1003715(2013).
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:23950735). 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 (By
CC similarity). The protease activity is required for proteolytic
CC activation of atg8: cleaves the C-terminal amino acid of atg8 to reveal
CC a C-terminal glycine (PubMed:23950735). Atg8 ubiquitin-like activity
CC requires the exposure of the glycine at the C-terminus for its
CC conjugation to phosphatidylethanolamine (PE) and its insertion to
CC membranes, which is necessary for autophagy. The atg8-PE conjugate
CC mediates tethering between adjacent membranes and stimulates membrane
CC hemifusion, leading to expansion of the autophagosomal membrane during
CC autophagy. In addition to the protease activity, also catalyzes
CC deconjugation of PE-conjugated forms of atg8 during macroautophagy:
CC atg8 delipidation is required to release the protein from membranes,
CC which facilitates multiple events during macroautophagy, and especially
CC for efficient 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). Plays a role in meiosis and
CC sporulation (PubMed:19778961). {ECO:0000250|UniProtKB:P53867,
CC ECO:0000269|PubMed:19778961, ECO:0000269|PubMed:23950735}.
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:0000269|PubMed:16823372}. Nucleus
CC {ECO:0000269|PubMed:16823372}. Preautophagosomal structure
CC {ECO:0000250|UniProtKB:P53867}.
CC -!- DISRUPTION PHENOTYPE: Impairs atg8-processing.
CC {ECO:0000269|PubMed:23950735}.
CC -!- SIMILARITY: Belongs to the peptidase C54 family. {ECO:0000305}.
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DR EMBL; CU329670; CAC00556.1; -; Genomic_DNA.
DR RefSeq; NP_594771.1; NM_001020198.2.
DR AlphaFoldDB; Q9P373; -.
DR SMR; Q9P373; -.
DR BioGRID; 278657; 15.
DR STRING; 4896.SPAC19B12.08.1; -.
DR MEROPS; C54.A07; -.
DR PaxDb; Q9P373; -.
DR EnsemblFungi; SPAC19B12.08.1; SPAC19B12.08.1:pep; SPAC19B12.08.
DR GeneID; 2542182; -.
DR KEGG; spo:SPAC19B12.08; -.
DR PomBase; SPAC19B12.08; atg4.
DR VEuPathDB; FungiDB:SPAC19B12.08; -.
DR eggNOG; KOG2674; Eukaryota.
DR HOGENOM; CLU_021259_5_2_1; -.
DR InParanoid; Q9P373; -.
DR OMA; CHTRRIR; -.
DR PhylomeDB; Q9P373; -.
DR PRO; PR:Q9P373; -.
DR Proteomes; UP000002485; Chromosome I.
DR GO; GO:0005829; C:cytosol; HDA:PomBase.
DR GO; GO:0005634; C:nucleus; HDA:PomBase.
DR GO; GO:0000407; C:phagophore assembly site; IEA:UniProtKB-SubCell.
DR GO; GO:0019786; F:Atg8-specific peptidase activity; ISO:PomBase.
DR GO; GO:0000045; P:autophagosome assembly; ISO:PomBase.
DR GO; GO:0006914; P:autophagy; IMP:PomBase.
DR GO; GO:0016236; P:macroautophagy; IMP:PomBase.
DR GO; GO:0070647; P:protein modification by small protein conjugation or removal; IC:PomBase.
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; Ubl conjugation pathway.
FT CHAIN 1..320
FT /note="Probable cysteine protease atg4"
FT /id="PRO_0000215868"
FT ACT_SITE 74
FT /note="Nucleophile"
FT /evidence="ECO:0000250|UniProtKB:Q9Y4P1"
FT ACT_SITE 232
FT /evidence="ECO:0000250|UniProtKB:Q9Y4P1"
FT ACT_SITE 234
FT /evidence="ECO:0000250|UniProtKB:Q9Y4P1"
SQ SEQUENCE 320 AA; 36929 MW; 47CE9E64C7E55F18 CRC64;
MELMARFLER YLHFAPTNTE PPGTLIWFLG HSYKIEDSQW PEKFLYDSFS LITITYRSGI
EGLENMTSDT GWGCMIRSTQ TLLANCLRIC YPEKQLKEIL ALFADEPSAP FSIHQFVTMG
KTLCDINPGQ WFGPTTSCSC VARLSDQNPD VPLHVYVARN GNAIYRDQLS KVSFPVLLLI
PTRLGIDSIN ESYYDQLLQV FEIRSFVGIT GGRPRSAHYF YARQNQYFFY LDPHCTHFAH
TTTQPASEET FHSATLRRVA IQDLDPCMIF GFLIRDEEEW HSFEANQKYF ADIVQIFDSE
PQPVETHDDF VLDENVEDHL
