ATG4B_CHICK
ID ATG4B_CHICK Reviewed; 393 AA.
AC Q6PZ02; Q5ZK72;
DT 15-MAR-2005, integrated into UniProtKB/Swiss-Prot.
DT 05-JUL-2004, sequence version 1.
DT 03-AUG-2022, entry version 102.
DE RecName: Full=Cysteine protease ATG4B {ECO:0000305};
DE EC=3.4.22.- {ECO:0000269|PubMed:15140988};
DE AltName: Full=Autophagy-related cysteine endopeptidase 2B {ECO:0000250|UniProtKB:Q9Y4P1};
DE Short=Autophagin-2B {ECO:0000250|UniProtKB:Q9Y4P1};
DE Short=cAut2B {ECO:0000303|PubMed:15140988};
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},
GN AUT2B {ECO:0000303|PubMed:15140988};
GN ORFNames=RCJMB04_12m14 {ECO:0000303|PubMed:15642098};
OS Gallus gallus (Chicken).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
OC Archelosauria; Archosauria; Dinosauria; Saurischia; Theropoda;
OC Coelurosauria; Aves; Neognathae; Galloanserae; Galliformes; Phasianidae;
OC Phasianinae; Gallus.
OX NCBI_TaxID=9031;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), AND FUNCTION.
RX PubMed=15140988; DOI=10.1128/jvi.78.11.5900-5912.2004;
RA Fricke J., Voss C., Thumm M., Meyers G.;
RT "Processing of a pestivirus protein by a cellular protease specific for
RT light chain 3 of microtubule-associated proteins.";
RL J. Virol. 78:5900-5912(2004).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2).
RC STRAIN=CB; TISSUE=Bursa of Fabricius;
RX PubMed=15642098; DOI=10.1186/gb-2004-6-1-r6;
RA Caldwell R.B., Kierzek A.M., Arakawa H., Bezzubov Y., Zaim J., Fiedler P.,
RA Kutter S., Blagodatski A., Kostovska D., Koter M., Plachy J., Carninci P.,
RA Hayashizaki Y., Buerstedde J.-M.;
RT "Full-length cDNAs from chicken bursal lymphocytes to facilitate gene
RT function analysis.";
RL Genome Biol. 6:R6.1-R6.9(2005).
CC -!- FUNCTION: Cysteine protease that plays a key role in autophagy by
CC mediating both proteolytic activation and delipidation of ATG8 family
CC proteins (PubMed:15140988). Required for canonical autophagy
CC (macroautophagy), non-canonical autophagy as well as for mitophagy. The
CC protease activity is required for proteolytic activation of ATG8 family
CC proteins: cleaves the C-terminal amino acid of ATG8 proteins to reveal
CC a C-terminal glycine. Exposure of the glycine at the C-terminus is
CC essential for ATG8 proteins conjugation to phosphatidylethanolamine
CC (PE) and insertion to membranes, which is necessary for autophagy.
CC Protease activity is also required to counteract formation of high-
CC molecular 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 ECO:0000269|PubMed:15140988}.
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 -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=Q6PZ02-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q6PZ02-2; Sequence=VSP_013035, VSP_013036;
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; AY570552; AAS78584.1; -; mRNA.
DR EMBL; AJ720212; CAG31871.1; -; mRNA.
DR RefSeq; NP_998738.1; NM_213573.1. [Q6PZ02-1]
DR AlphaFoldDB; Q6PZ02; -.
DR SMR; Q6PZ02; -.
DR STRING; 9031.ENSGALP00000010165; -.
DR MEROPS; C54.003; -.
DR PaxDb; Q6PZ02; -.
DR Ensembl; ENSGALT00000010179; ENSGALP00000010165; ENSGALG00000006298. [Q6PZ02-1]
DR Ensembl; ENSGALT00000105472; ENSGALP00000072484; ENSGALG00000006298. [Q6PZ02-1]
DR GeneID; 404750; -.
DR KEGG; gga:404750; -.
DR CTD; 23192; -.
DR VEuPathDB; HostDB:geneid_404750; -.
DR eggNOG; KOG2674; Eukaryota.
DR GeneTree; ENSGT00530000063000; -.
DR InParanoid; Q6PZ02; -.
DR OMA; CHTRRIR; -.
DR OrthoDB; 431748at2759; -.
DR PhylomeDB; Q6PZ02; -.
DR PRO; PR:Q6PZ02; -.
DR Proteomes; UP000000539; Chromosome 9.
DR Bgee; ENSGALG00000006298; Expressed in brain and 13 other tissues.
DR ExpressionAtlas; Q6PZ02; baseline and differential.
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 Alternative splicing; Autophagy; Cytoplasm; Cytoplasmic vesicle;
KW Endoplasmic reticulum; Hydrolase; Mitochondrion; Protease;
KW Protein transport; Reference proteome; Thiol protease; Transport;
KW Ubl conjugation pathway.
FT CHAIN 1..393
FT /note="Cysteine protease ATG4B"
FT /id="PRO_0000215846"
FT MOTIF 388..391
FT /note="LIR"
FT /evidence="ECO:0000250|UniProtKB:Q9Y4P1"
FT ACT_SITE 73
FT /note="Nucleophile"
FT /evidence="ECO:0000250|UniProtKB:Q9Y4P1"
FT ACT_SITE 278
FT /evidence="ECO:0000250|UniProtKB:Q9Y4P1"
FT ACT_SITE 280
FT /evidence="ECO:0000250|UniProtKB:Q9Y4P1"
FT VAR_SEQ 320..343
FT /note="GFFCHTEEDFNDWCHQIKKLSLVR -> VCSCCLFSTQLRNSRSLLTGTWLR
FT (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:15642098"
FT /id="VSP_013035"
FT VAR_SEQ 344..393
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:15642098"
FT /id="VSP_013036"
FT CONFLICT 29
FT /note="G -> C (in Ref. 2; CAG31871)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 393 AA; 44531 MW; 2C3479C168DE062C CRC64;
MDAATLTYDT LRFEYEDFPE TKEPVWILGR KYSVFTEKEE ILLDVTSRLW FTYRKNFPAI
GGTGPTSDTG WGCMLRCGQM IFAQALVCRH LGRDWRWIKG KRQTDNYFSV LNAFIDKKDS
YYSIHQIAQM GVGEGKSIGQ WYGPNTVAQV LKKLATFDTW SSLAVHIAMD NTVVMEEIRR
LCQSNFSCAG AAACPAVEAD VLYNGYPEEA GVRDKLSLWK PLVLLIPLRL GLTEINEAYI
ETLKHCFMMP QSLGVIGGKP NSAHYFIGYV GEELIYLDPH TTQPAVEPSD SGCLPDESFH
CQHPPCRMSI AELDPSIAVG FFCHTEEDFN DWCHQIKKLS LVRGALPMFE LVERQPSHFS
NPDVLNLTPD SSDADRLERF FDSEDEDFEI LSL
