ATG4B_XENLA
ID ATG4B_XENLA Reviewed; 384 AA.
AC Q640G7;
DT 15-MAR-2005, integrated into UniProtKB/Swiss-Prot.
DT 25-OCT-2004, sequence version 1.
DT 03-AUG-2022, entry version 65.
DE RecName: Full=Cysteine protease ATG4B {ECO:0000305};
DE EC=3.4.22.- {ECO:0000250|UniProtKB:Q9Y4P1};
DE AltName: Full=Autophagy-related protein 4 homolog B {ECO:0000250|UniProtKB:Q9Y4P1};
GN Name=atg4b {ECO:0000250|UniProtKB:Q9Y4P1};
GN Synonyms=apg4b {ECO:0000250|UniProtKB:Q9Y4P1};
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].
RG NIH - Xenopus Gene Collection (XGC) project;
RL Submitted (SEP-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. Required for canonical autophagy (macroautophagy), non-
CC canonical autophagy as well as for mitophagy. The protease activity is
CC required for proteolytic activation of ATG8 family proteins: cleaves
CC the C-terminal amino acid of ATG8 proteins to reveal a C-terminal
CC glycine. Exposure of the glycine at the C-terminus is essential for
CC ATG8 proteins conjugation to phosphatidylethanolamine (PE) and
CC insertion to membranes, which is necessary for autophagy. Protease
CC activity is also required to counteract formation of high-molecular
CC weight conjugates of ATG8 proteins (ATG8ylation): acts as a
CC deubiquitinating-like enzyme that removes ATG8 conjugated to other
CC proteins, such as ATG3. In addition to the protease activity, also
CC mediates delipidation of ATG8 family proteins. Catalyzes delipidation
CC of PE-conjugated forms of ATG8 proteins during macroautophagy. Also
CC involved in non-canonical autophagy, a parallel pathway involving
CC conjugation of ATG8 proteins to single membranes at endolysosomal
CC compartments, by catalyzing delipidation of ATG8 proteins conjugated to
CC phosphatidylserine (PS). {ECO:0000250|UniProtKB:Q9Y4P1}.
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:Q9Y4P1};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:67549;
CC Evidence={ECO:0000250|UniProtKB:Q9Y4P1};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=[protein]-C-terminal L-amino acid-glycyl-phosphatidylserine +
CC H2O = [protein]-C-terminal L-amino acid-glycine + a 1,2-diacyl-sn-
CC glycero-3-phospho-L-serine; Xref=Rhea:RHEA:67576, Rhea:RHEA-
CC COMP:17324, Rhea:RHEA-COMP:17326, ChEBI:CHEBI:15377,
CC ChEBI:CHEBI:57262, ChEBI:CHEBI:172940, ChEBI:CHEBI:172942;
CC Evidence={ECO:0000250|UniProtKB:Q9Y4P1};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:67577;
CC Evidence={ECO:0000250|UniProtKB:Q9Y4P1};
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000250|UniProtKB:Q9Y4P1}.
CC Cytoplasm, cytosol {ECO:0000250|UniProtKB:Q9Y4P1}. Cytoplasmic vesicle,
CC autophagosome {ECO:0000250|UniProtKB:Q9Y4P1}. Endoplasmic reticulum
CC {ECO:0000250|UniProtKB:Q9Y4P1}. Mitochondrion
CC {ECO:0000250|UniProtKB:Q9Y4P1}. Note=Mainly localizes to the cytoplasm,
CC including cytosol. {ECO:0000250|UniProtKB:Q9Y4P1}.
CC -!- DOMAIN: The LIR motif (LC3-interacting region) is required for the
CC interaction with ATG8 family proteins. Required for proteolytic
CC activation and delipidation of ATG8 proteins.
CC {ECO:0000250|UniProtKB:Q9Y4P1}.
CC -!- SIMILARITY: Belongs to the peptidase C54 family. {ECO:0000305}.
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DR EMBL; BC082660; AAH82660.1; -; mRNA.
DR RefSeq; NP_001088025.1; NM_001094556.1.
DR AlphaFoldDB; Q640G7; -.
DR SMR; Q640G7; -.
DR MEROPS; C54.003; -.
DR DNASU; 494717; -.
DR GeneID; 494717; -.
DR KEGG; xla:494717; -.
DR CTD; 494717; -.
DR Xenbase; XB-GENE-967116; atg4b.L.
DR OrthoDB; 431748at2759; -.
DR Proteomes; UP000186698; Chromosome 5L.
DR Bgee; 494717; Expressed in pancreas and 20 other tissues.
DR GO; GO:0005776; C:autophagosome; IEA:UniProtKB-SubCell.
DR GO; GO:0031410; C:cytoplasmic vesicle; IEA:UniProtKB-KW.
DR GO; GO:0005829; C:cytosol; IEA:UniProtKB-SubCell.
DR GO; GO:0005783; C:endoplasmic reticulum; IEA:UniProtKB-SubCell.
DR GO; GO:0005739; C:mitochondrion; IEA:UniProtKB-SubCell.
DR GO; GO:0004197; F:cysteine-type endopeptidase activity; IEA:InterPro.
DR GO; GO:0006914; P:autophagy; ISS:UniProtKB.
DR GO; GO:0016237; P:lysosomal microautophagy; ISS:UniProtKB.
DR GO; GO:0000423; P:mitophagy; ISS:UniProtKB.
DR GO; GO:0031173; P:otolith mineralization completed early in development; ISS:UniProtKB.
DR GO; GO:0015031; P:protein transport; IEA:UniProtKB-KW.
DR GO; GO:0006508; P:proteolysis; IEA:UniProtKB-KW.
DR InterPro; IPR032916; ATG4B_met.
DR InterPro; IPR038765; Papain-like_cys_pep_sf.
DR InterPro; IPR005078; Peptidase_C54.
DR PANTHER; PTHR22624; PTHR22624; 1.
DR PANTHER; PTHR22624:SF39; PTHR22624:SF39; 1.
DR Pfam; PF03416; Peptidase_C54; 1.
DR SUPFAM; SSF54001; SSF54001; 1.
PE 2: Evidence at transcript level;
KW Autophagy; Cytoplasm; Cytoplasmic vesicle; Endoplasmic reticulum;
KW Hydrolase; Mitochondrion; Protease; Protein transport; Reference proteome;
KW Thiol protease; Transport; Ubl conjugation pathway.
FT CHAIN 1..384
FT /note="Cysteine protease ATG4B"
FT /id="PRO_0000215848"
FT MOTIF 379..382
FT /note="LIR"
FT /evidence="ECO:0000250|UniProtKB:Q9Y4P1"
FT ACT_SITE 74
FT /note="Nucleophile"
FT /evidence="ECO:0000250|UniProtKB:Q9Y4P1"
FT ACT_SITE 269
FT /evidence="ECO:0000250|UniProtKB:Q9Y4P1"
FT ACT_SITE 271
FT /evidence="ECO:0000250|UniProtKB:Q9Y4P1"
SQ SEQUENCE 384 AA; 43158 MW; 6D20C22FF8D2FC00 CRC64;
MDAATLTYDT LRFADTPDFP ETAEPVWVLG RKYSALTEKE QLLNDITSRL WFTYRRNFQA
IGGTGPTSDT GWGCMLRCGQ MIFAQALICR HVGRDWRWDK QKPKGEYLNI LTAFLDKKDS
YYSIHQIAQM GVGEGKYIGQ WYGPNTVAQV LRKLAVFDQW SSIAVHIAMD NTVVVDEIRR
LCRAGSGESS DAGALSNGYT GDSDPSCAQW KPLVLLIPLR LGLSEINEAY IETLKHCFMV
PQSLGVIGGR PNSAHYFIGY VGDELIYLDP HTTQLSVEPS DCSFIEDESF HCQHPPCRMH
VSEIDPSIAV GFFCSSQEDF EDWCQHIKKL SLSGGALPMF EVVDQLPLHL SNPDVLNLTP
DSSDADRLDR FFDSEDEEFE ILSL
