ID   ATG4A_XENLA             Reviewed;         397 AA.
AC   Q6GPU1;
DT   15-MAR-2005, integrated into UniProtKB/Swiss-Prot.
DT   19-JUL-2004, sequence version 1.
DT   03-AUG-2022, entry version 68.
DE   RecName: Full=Cysteine protease ATG4A {ECO:0000305};
DE            EC=3.4.22.- {ECO:0000250|UniProtKB:Q8WYN0};
DE   AltName: Full=Autophagy-related protein 4 homolog A {ECO:0000250|UniProtKB:Q8WYN0};
GN   Name=atg4a {ECO:0000250|UniProtKB:Q8WYN0};
GN   Synonyms=apg4a {ECO:0000250|UniProtKB:Q8WYN0};
OS   Xenopus laevis (African clawed frog).
OC   Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Amphibia;
OC   Batrachia; Anura; Pipoidea; Pipidae; Xenopodinae; Xenopus; Xenopus.
OX   NCBI_TaxID=8355;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC   TISSUE=Ovary;
RG   NIH - Xenopus Gene Collection (XGC) project;
RL   Submitted (JUN-2004) to the EMBL/GenBank/DDBJ databases.
CC   -!- FUNCTION: Cysteine protease that plays a key role in autophagy by
CC       mediating both proteolytic activation and delipidation of ATG8 family
CC       proteins. The protease activity is required for proteolytic activation
CC       of ATG8 family proteins: cleaves the C-terminal amino acid of ATG8
CC       proteins to reveal a C-terminal glycine. Exposure of the glycine at the
CC       C-terminus is essential for ATG8 proteins conjugation to
CC       phosphatidylethanolamine (PE) and insertion to membranes, which is
CC       necessary for autophagy. Protease activity is also required to
CC       counteract formation of high-molecular weight conjugates of ATG8
CC       proteins (ATG8ylation): acts as a deubiquitinating-like enzyme that
CC       removes ATG8 conjugated to other proteins, such as ATG3. In addition to
CC       the protease activity, also mediates delipidation of ATG8 family
CC       proteins. Catalyzes delipidation of PE-conjugated forms of ATG8
CC       proteins during macroautophagy. {ECO:0000250|UniProtKB:Q8WYN0}.
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:Q8WYN0};
CC       PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:67549;
CC         Evidence={ECO:0000250|UniProtKB:Q8WYN0};
CC   -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000250|UniProtKB:Q8BGE6}.
CC   -!- DOMAIN: The LIR motif (LC3-interacting region) is required for the
CC       interaction with the ATG8 family proteins. Required for proteolytic
CC       activation and delipidation of ATG8 proteins.
CC       {ECO:0000250|UniProtKB:Q8WYN0}.
CC   -!- SIMILARITY: Belongs to the peptidase C54 family. {ECO:0000305}.
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DR   EMBL; BC073017; AAH73017.1; -; mRNA.
DR   RefSeq; XP_018085361.1; XM_018229872.1.
DR   AlphaFoldDB; Q6GPU1; -.
DR   SMR; Q6GPU1; -.
DR   MEROPS; C54.002; -.
DR   GeneID; 108698409; -.
DR   KEGG; xla:108698409; -.
DR   Xenbase; XB-GENE-922684; atg4a.L.
DR   OMA; DIRTMAF; -.
DR   OrthoDB; 431748at2759; -.
DR   Proteomes; UP000186698; Chromosome 8L.
DR   Bgee; 108698409; Expressed in muscle tissue and 19 other tissues.
DR   GO; GO:0005737; C:cytoplasm; IEA:UniProtKB-SubCell.
DR   GO; GO:0019786; F:Atg8-specific peptidase activity; ISS:UniProtKB.
DR   GO; GO:0004197; F:cysteine-type endopeptidase activity; IEA:InterPro.
DR   GO; GO:0008234; F:cysteine-type peptidase activity; ISS:UniProtKB.
DR   GO; GO:0006914; P:autophagy; ISS:UniProtKB.
DR   GO; GO:0006629; P:lipid metabolic process; IEA:UniProtKB-KW.
DR   GO; GO:0051697; P:protein delipidation; ISS:UniProtKB.
DR   GO; GO:0015031; P:protein transport; IEA:UniProtKB-KW.
DR   GO; GO:0006508; P:proteolysis; IEA:UniProtKB-KW.
DR   InterPro; IPR033474; ATG4A.
DR   InterPro; IPR038765; Papain-like_cys_pep_sf.
DR   InterPro; IPR005078; Peptidase_C54.
DR   PANTHER; PTHR22624; PTHR22624; 1.
DR   PANTHER; PTHR22624:SF35; PTHR22624:SF35; 1.
DR   Pfam; PF03416; Peptidase_C54; 1.
DR   SUPFAM; SSF54001; SSF54001; 1.
PE   2: Evidence at transcript level;
KW   Autophagy; Cytoplasm; Hydrolase; Lipid metabolism; Protease;
KW   Protein transport; Reference proteome; Thiol protease; Transport;
KW   Ubl conjugation pathway.
FT   CHAIN           1..397
FT                   /note="Cysteine protease ATG4A"
FT                   /id="PRO_0000215842"
FT   MOTIF           392..395
FT                   /note="LIR"
FT                   /evidence="ECO:0000250|UniProtKB:Q8WYN0"
FT   ACT_SITE        79
FT                   /note="Nucleophile"
FT                   /evidence="ECO:0000250|UniProtKB:Q9Y4P1"
FT   ACT_SITE        279
FT                   /evidence="ECO:0000250|UniProtKB:Q9Y4P1"
FT   ACT_SITE        281
FT                   /evidence="ECO:0000250|UniProtKB:Q9Y4P1"
SQ   SEQUENCE   397 AA;  45298 MW;  F27EAC1335D045FC CRC64;
     MDSDPVSDYL KYENEPEYLD LEELPDSDEP VYILGKQYDT KTDKCDLQSD IVSRLWFTYR
     KKFSPIGGTG PSSDTGWGCM LRCGQMMLAQ ALVCQHLGRD WRWEKHKNHP EEYQQILQCF
     LDRKDCCYSI HQMAQMGVGE GKSIGEWFGP NTVAQVLKKL ALFDEWNSLA VYVSMDNTVV
     VEDIKTMCKY QPQSCSMAQA ASHQSTWSRC RDTSGHCSGW RPLLLVVPLR LGINHINPVY
     VDAFKACFKM PQSLGALGGK PNHAYYFIGF SGDEIIYLDP HTTQTFVDTE EAGTVQDQTY
     HCQKGPNSMK VLNLDPSVAL GFFCKDENDF NNWCEVIEKE ILKHQSLRMF ELTPKHPPHW
     PPFIPPTKPE VTTTGAELIE STDKLFDVEE EFEILSV