ATG4_CRYNB
ID ATG4_CRYNB Reviewed; 1193 AA.
AC P0CQ11; Q55JY1; Q5K9L9;
DT 28-JUN-2011, integrated into UniProtKB/Swiss-Prot.
DT 28-JUN-2011, sequence version 1.
DT 03-AUG-2022, entry version 40.
DE RecName: Full=Cysteine protease ATG4;
DE EC=3.4.22.-;
DE AltName: Full=Autophagy-related protein 4;
GN Name=ATG4; OrderedLocusNames=CNBK2020;
OS Cryptococcus neoformans var. neoformans serotype D (strain B-3501A)
OS (Filobasidiella neoformans).
OC Eukaryota; Fungi; Dikarya; Basidiomycota; Agaricomycotina; Tremellomycetes;
OC Tremellales; Cryptococcaceae; Cryptococcus;
OC Cryptococcus neoformans species complex.
OX NCBI_TaxID=283643;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=B-3501A;
RX PubMed=15653466; DOI=10.1126/science.1103773;
RA Loftus B.J., Fung E., Roncaglia P., Rowley D., Amedeo P., Bruno D.,
RA Vamathevan J., Miranda M., Anderson I.J., Fraser J.A., Allen J.E.,
RA Bosdet I.E., Brent M.R., Chiu R., Doering T.L., Donlin M.J., D'Souza C.A.,
RA Fox D.S., Grinberg V., Fu J., Fukushima M., Haas B.J., Huang J.C.,
RA Janbon G., Jones S.J.M., Koo H.L., Krzywinski M.I., Kwon-Chung K.J.,
RA Lengeler K.B., Maiti R., Marra M.A., Marra R.E., Mathewson C.A.,
RA Mitchell T.G., Pertea M., Riggs F.R., Salzberg S.L., Schein J.E.,
RA Shvartsbeyn A., Shin H., Shumway M., Specht C.A., Suh B.B., Tenney A.,
RA Utterback T.R., Wickes B.L., Wortman J.R., Wye N.H., Kronstad J.W.,
RA Lodge J.K., Heitman J., Davis R.W., Fraser C.M., Hyman R.W.;
RT "The genome of the basidiomycetous yeast and human pathogen Cryptococcus
RT neoformans.";
RL Science 307:1321-1324(2005).
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}.
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DR EMBL; AAEY01000052; EAL18184.1; -; Genomic_DNA.
DR RefSeq; XP_772831.1; XM_767738.1.
DR AlphaFoldDB; P0CQ11; -.
DR SMR; P0CQ11; -.
DR EnsemblFungi; AAW46309; AAW46309; CNK01520.
DR EnsemblFungi; EAL18184; EAL18184; CNBK2020.
DR GeneID; 4938899; -.
DR KEGG; cnb:CNBK2020; -.
DR VEuPathDB; FungiDB:CNBK2020; -.
DR HOGENOM; CLU_005225_0_0_1; -.
DR Proteomes; UP000001435; Chromosome 11.
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; 2.
PE 3: Inferred from homology;
KW Autophagy; Cytoplasm; Hydrolase; Nucleus; Protease; Protein transport;
KW Thiol protease; Transport.
FT CHAIN 1..1193
FT /note="Cysteine protease ATG4"
FT /id="PRO_0000410215"
FT REGION 23..284
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 358..474
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 807..869
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 899..924
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 1000..1171
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 33..48
FT /note="Pro residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 58..76
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 101..153
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 155..284
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 390..451
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 811..825
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 904..924
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1003..1026
FT /note="Acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1037..1062
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1102..1116
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1130..1155
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT ACT_SITE 570
FT /note="Nucleophile"
FT /evidence="ECO:0000250|UniProtKB:Q9Y4P1"
FT ACT_SITE 789
FT /evidence="ECO:0000250|UniProtKB:Q9Y4P1"
FT ACT_SITE 791
FT /evidence="ECO:0000250|UniProtKB:Q9Y4P1"
SQ SEQUENCE 1193 AA; 130136 MW; ECD91DB1D9543F25 CRC64;
MSSPTSTSPK SSFVFSPTSF PHAAIASNNV RPRTNLPPPP PPDRIPPPKG RSHQQKFKIL
RKEKDKDRRQ PIDLEDDWTI EDVTVNGDGV EQESQYLDDL QPEENELKPG PRFLEMANRE
EKKEKTSKSR GLVKKTSRLF GRDKDKDRGK PEEPAVTGSS SSTLAAMRQS SSTSTDSTTS
RSITSAFTRQ NSIQSRRSPR TSFGQAHSRR ASQDSQMSWP APRSIRSSTT SHDPSSDPQN
SASSTGVPIP QRQGASMSSL SRYSLPHPNG GTSRSPDTFP NKMSTWFSHL LPVSSGSPPS
SSYETSSSIR KQSSVAASLF NAARQKAVDG VRHLLDSEAQ PDKCMDTIWV RGVAHPGWRP
ITPENSTSNL PALEPGGSGG GVEDRRASLS MNGPSPNSLR PSSWKRNTSL PPTGQPQSPA
HVHTQASNQT TSPSKGFTGI WNPSTLSLGM PIGGSPNKEK ENGSGAESPS KKKSKEIVKW
PEQFYDDFKS TVWFTYRNQY APISSLSPNL LIPSPEAYYA SFGPPLDATS PSSLRVTTPT
AAAQQSASGS GGWGWSKEER GLTSDAGWGC MLRTGQSLLV NALIHIHLGR DWRVPSTPAS
FSEATTTQEI AALKDYAKYA QMLSWFLDDP SPLCPFSVHR MALIGKELGK EVGEWFGPST
AAGALKTLAN SFAPCGVAVA TATDSIIYKS DVYTASNLPS DDWNSISPTF NSSKKKRRGD
NEAKEEKWGK RAVLILVGVR LGLDGVNPIY YDSIKALFTF PQSVGIAGGR PSSSYYFVGS
QANHLFYLDP HLTRPAIPLQ IPPLPVHSAK EKGSTESSSI MSTAEEESEE GVMIRTPETP
RSTTPSMFSA PEHVEDEDQE EWGQGSKYKL DVVDADGVEV EGIDDDKGRN EGKMIREEVP
KSSFESNGAA QEQPKKQKGF TSTASIDSQV DSQVDPHMLW YTTAYPDPLL RTYHCEKIKK
MPLSGLDPSM LLGFVCKDED DFEDFVERVA QLPKKIFTVQ DEMPSWEEDD DAGLESVSEP
DFEGDEFEEP GTAKPRFDSS SPVNEDSLKG PRVVSASTTA TPLAAKEEDH LDVEEANSTD
DDNESIGTTT AAGPMDIARH LNRVDLSSKR EQEGDDDDGE WVGGTPSSQG VLVEPPSLKG
TPSKSRSSAF EPRYEQNGET EQERPVFPAR NRMESWVEPV CEGKEAPNGD NLL
