ATG42_CAEEL
ID ATG42_CAEEL Reviewed; 521 AA.
AC Q9U1N6;
DT 13-NOV-2019, integrated into UniProtKB/Swiss-Prot.
DT 01-MAY-2000, sequence version 1.
DT 03-AUG-2022, entry version 135.
DE RecName: Full=Cysteine protease atg-4.2 {ECO:0000305};
DE EC=3.4.22.- {ECO:0000255|RuleBase:RU363115, ECO:0000269|PubMed:22767594};
DE AltName: Full=Autophagy-related protein 4 homolog 2 {ECO:0000305};
GN Name=atg-4.2 {ECO:0000312|WormBase:ZK792.8};
GN ORFNames=ZK792.8 {ECO:0000312|WormBase:ZK792.8};
OS Caenorhabditis elegans.
OC Eukaryota; Metazoa; Ecdysozoa; Nematoda; Chromadorea; Rhabditida;
OC Rhabditina; Rhabditomorpha; Rhabditoidea; Rhabditidae; Peloderinae;
OC Caenorhabditis.
OX NCBI_TaxID=6239 {ECO:0000312|Proteomes:UP000001940};
RN [1] {ECO:0000312|Proteomes:UP000001940}
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=Bristol N2 {ECO:0000312|Proteomes:UP000001940};
RX PubMed=9851916; DOI=10.1126/science.282.5396.2012;
RG The C. elegans sequencing consortium;
RT "Genome sequence of the nematode C. elegans: a platform for investigating
RT biology.";
RL Science 282:2012-2018(1998).
RN [2] {ECO:0000305}
RP FUNCTION, CATALYTIC ACTIVITY, AND BIOPHYSICOCHEMICAL PROPERTIES.
RX PubMed=22767594; DOI=10.1074/jbc.m112.365676;
RA Wu F., Li Y., Wang F., Noda N.N., Zhang H.;
RT "Differential function of the two Atg4 homologues in the aggrephagy pathway
RT in Caenorhabditis elegans.";
RL J. Biol. Chem. 287:29457-29467(2012).
RN [3] {ECO:0000305}
RP FUNCTION, SUBCELLULAR LOCATION, AND MUTAGENESIS OF 84-LYS--LEU-521;
RP 201-TRP--LEU-521 AND GLY-373.
RX PubMed=30880001; DOI=10.1016/j.devcel.2019.02.013;
RA Hill S.E., Kauffman K.J., Krout M., Richmond J.E., Melia T.J.,
RA Colon-Ramos D.A.;
RT "Maturation and Clearance of Autophagosomes in Neurons Depends on a
RT Specific Cysteine Protease Isoform, ATG-4.2.";
RL Dev. Cell 49:251-266(2019).
CC -!- FUNCTION: Cysteine protease required for autophagy (PubMed:22767594,
CC PubMed:30880001). Cleaves the C-terminal amino acid of ATG8 family
CC proteins lgg-1, to reveal a C-terminal glycine (Probable). Exposure of
CC the glycine at the C-terminus is essential for ATG8 proteins
CC conjugation to phosphatidylethanolamine (PE) and insertion to
CC membranes, which is necessary for autophagy (Probable). Its cleavage
CC activity is functionally redundant to atg-4.1, but it cleaves lgg-1
CC precursors less efficiently than atg-4.1 (Probable). In contrast to
CC atg-4.1, plays a more significant role in the later phases of autophagy
CC and in addition has a role in autophagosome maturation
CC (PubMed:30880001). Acts redundantly with atg-4.1 to promote the lgg-1
CC delipidation to release the protein from membranes, which facilitates
CC multiple events during macroautophagy (PubMed:30880001). Regulates the
CC accumulation of autophagic structures in neurons and is specifically,
CC required for the maturation and elimination of autophagosomes from the
CC synaptic region of AIY interneurons (PubMed:30880001).
CC {ECO:0000269|PubMed:22767594, ECO:0000269|PubMed:30880001,
CC ECO:0000305|PubMed:22767594}.
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 -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC Kinetic parameters:
CC KM=20.7 uM for lgg-1 {ECO:0000269|PubMed:22767594};
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000255|RuleBase:RU363115,
CC ECO:0000269|PubMed:30880001}.
CC -!- SIMILARITY: Belongs to the peptidase C54 family.
CC {ECO:0000255|RuleBase:RU363115}.
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DR EMBL; BX284604; CAB54515.1; -; Genomic_DNA.
DR PIR; T27996; T27996.
DR RefSeq; NP_502208.1; NM_069807.3.
DR AlphaFoldDB; Q9U1N6; -.
DR SMR; Q9U1N6; -.
DR IntAct; Q9U1N6; 1.
DR STRING; 6239.ZK792.8; -.
DR MEROPS; C54.009; -.
DR EPD; Q9U1N6; -.
DR PaxDb; Q9U1N6; -.
DR PeptideAtlas; Q9U1N6; -.
DR EnsemblMetazoa; ZK792.8.1; ZK792.8.1; WBGene00014080.
DR GeneID; 3565022; -.
DR KEGG; cel:CELE_ZK792.8; -.
DR UCSC; ZK792.8; c. elegans.
DR CTD; 3565022; -.
DR WormBase; ZK792.8; CE24740; WBGene00014080; atg-4.2.
DR eggNOG; KOG2674; Eukaryota.
DR GeneTree; ENSGT00530000063000; -.
DR HOGENOM; CLU_523002_0_0_1; -.
DR InParanoid; Q9U1N6; -.
DR OMA; EAVFIMK; -.
DR OrthoDB; 431748at2759; -.
DR PhylomeDB; Q9U1N6; -.
DR Reactome; R-CEL-1632852; Macroautophagy.
DR PRO; PR:Q9U1N6; -.
DR Proteomes; UP000001940; Chromosome IV.
DR Bgee; WBGene00014080; Expressed in embryo and 4 other tissues.
DR GO; GO:0005737; C:cytoplasm; IEA:UniProtKB-SubCell.
DR GO; GO:0004197; F:cysteine-type endopeptidase activity; IDA:WormBase.
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; 2.
DR Pfam; PF03416; Peptidase_C54; 1.
DR SUPFAM; SSF54001; SSF54001; 1.
PE 1: Evidence at protein level;
KW Autophagy; Cytoplasm; Hydrolase; Protease; Protein transport;
KW Reference proteome; Thiol protease; Transport.
FT CHAIN 1..521
FT /note="Cysteine protease atg-4.2"
FT /id="PRO_0000448584"
FT REGION 90..109
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 499..521
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT ACT_SITE 203
FT /note="Nucleophile"
FT /evidence="ECO:0000250|UniProtKB:Q9Y4P1"
FT ACT_SITE 394
FT /evidence="ECO:0000250|UniProtKB:Q9Y4P1"
FT ACT_SITE 396
FT /evidence="ECO:0000250|UniProtKB:Q9Y4P1"
FT MUTAGEN 84..521
FT /note="Missing: In gk430078; increases the number of lgg-1-
FT containing protein aggregates in neuronal cell bodies, but
FT not neurites, of AIY interneurons."
FT /evidence="ECO:0000269|PubMed:30880001"
FT MUTAGEN 201..521
FT /note="Missing: In gk628327; increases the number of lgg-1-
FT containing protein aggregates in neuronal cell bodies, but
FT not neurites, of AIY interneurons. Increases the number of
FT lgg-1-containing protein aggregates in neurites of AIY
FT interneurons in a unc-16 ju146 mutant background."
FT /evidence="ECO:0000269|PubMed:30880001"
FT MUTAGEN 373
FT /note="G->R: In ola316; defective maturation of
FT autophagosomes with increased numbers of immature
FT autophagic vacuoles. Increases the number of lgg-1-
FT containing protein aggregates in neuronal cell bodies, but
FT not neurites, of AIY interneurons. Increases the number of
FT lgg-1-containing protein aggregates in neurites of AIY
FT interneurons in a unc-16 ju146 mutant background."
FT /evidence="ECO:0000269|PubMed:30880001"
SQ SEQUENCE 521 AA; 59276 MW; 25AC45E2AAD4D614 CRC64;
MNNIPDDFKK IASSSRLPRK YCSSESSLSD DDGHEIEHVL KHGAPEEALT PDTERMVVLG
QDVVQSAPAS LVPGGNLSWM SKIKSAGASM MGSIRPSSSS QDVHSTGEIE KHSKKKWKAR
LWSTWNNIKY SSTWMSDRSD EYGGENDVVF LGRRYSTSVD ESGLRSGFEN FCSDYYSRLW
ITYRTDFPAL LDTDTTTDCG WGCMIRTTQM MVAQAIMVNR FGRDWRFTRR KRSHVAAHGD
EDDFDREKIQ EWMILKLFED KPTAPLGIHK MVGIAAMGKG KKAVGSWYSP SEAVFIMKKA
LTESSSPLTG NTAMLLSIDG RVHIRDIEVE TKNWMKKLIL VIVVRLGAAE LNPIYVPHLM
RLFAMESCLG ITGGRPDHSS WFVGYYGDQI IYLDPHVAHE YIPIDINPNT NVVDSDSKKA
KKCPEKSYHC RLLSKMHFFD MDPSCALCFQ FESREQFDND MRQLNLSQFI DIDQGEEHGM
KRVRDPMFSV VYGERRQPPS YEREVSETEQ AQADKHGFEM L
