ATG4B_DANRE
ID ATG4B_DANRE Reviewed; 394 AA.
AC Q6DG88;
DT 15-MAR-2005, integrated into UniProtKB/Swiss-Prot.
DT 15-MAR-2005, sequence version 2.
DT 03-AUG-2022, entry version 105.
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 Danio rerio (Zebrafish) (Brachydanio rerio).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
OC Actinopterygii; Neopterygii; Teleostei; Ostariophysi; Cypriniformes;
OC Danionidae; Danioninae; Danio.
OX NCBI_TaxID=7955;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RG NIH - Zebrafish Gene Collection (ZGC) project;
RL Submitted (JUL-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; BC076463; AAH76463.1; -; mRNA.
DR AlphaFoldDB; Q6DG88; -.
DR SMR; Q6DG88; -.
DR STRING; 7955.ENSDARP00000106508; -.
DR MEROPS; C54.003; -.
DR PaxDb; Q6DG88; -.
DR Ensembl; ENSDART00000121558; ENSDARP00000106508; ENSDARG00000052104.
DR ZFIN; ZDB-GENE-040917-3; atg4b.
DR eggNOG; KOG2674; Eukaryota.
DR GeneTree; ENSGT00530000063000; -.
DR HOGENOM; CLU_021259_0_1_1; -.
DR InParanoid; Q6DG88; -.
DR OMA; CHTRRIR; -.
DR PhylomeDB; Q6DG88; -.
DR TreeFam; TF314847; -.
DR Reactome; R-DRE-1632852; Macroautophagy.
DR PRO; PR:Q6DG88; -.
DR Proteomes; UP000000437; Genome assembly.
DR Proteomes; UP000814640; Chromosome 6.
DR Bgee; ENSDARG00000052104; Expressed in mature ovarian follicle and 22 other tissues.
DR ExpressionAtlas; Q6DG88; baseline.
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..394
FT /note="Cysteine protease ATG4B"
FT /id="PRO_0000215847"
FT MOTIF 389..392
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 280
FT /evidence="ECO:0000250|UniProtKB:Q9Y4P1"
FT ACT_SITE 282
FT /evidence="ECO:0000250|UniProtKB:Q9Y4P1"
SQ SEQUENCE 394 AA; 44453 MW; 430BB517CDEE08D8 CRC64;
MDAATLTYDS LRFGEIEDFP ETSDPVWILG KQFSALTEKD DILADVTSRL WFTYRKNFQP
IGGTGPTSDT GWGCMLRCGQ MILGEALICR HLGRDWKWSP GQRQRPEYVS ILNAFIDKKD
SYYSIHQIAQ MGVGEGKSIG QWYGPNTVAQ VLKKLAVFDS WSRLAVHVAM DNTVVIEEIK
RLCMPWLDFD RGACAVSEEP REMNGDLEGA CALAEEETAL WKPLVLLIPL RLGLSDINEA
YIEPLKQCFM MPQSLGVIGG KPNSAHYFIG FVGDELIYLD PHTTQPAVDP SEDGHFPDDS
YHCQHPPCRM HICELDPSIA AGFFCQTEDD FDDWCAQIRK VSNCRGLPMF ELVDSQPSHL
ITADVLNLTP DFSDSDRLER FFDSEDEEFE ILSL
