ATG41_CAEEL
ID ATG41_CAEEL Reviewed; 481 AA.
AC K8ESC5; Q9NA30;
DT 13-NOV-2019, integrated into UniProtKB/Swiss-Prot.
DT 06-FEB-2013, sequence version 1.
DT 03-AUG-2022, entry version 71.
DE RecName: Full=Cysteine protease atg-4.1 {ECO:0000305};
DE EC=3.4.22.- {ECO:0000255|RuleBase:RU363115, ECO:0000269|PubMed:22767594};
DE AltName: Full=Autophagy-related protein 4 homolog 1 {ECO:0000305};
GN Name=atg-4.1 {ECO:0000312|WormBase:Y87G2A.3b};
GN ORFNames=Y87G2A.3 {ECO:0000312|WormBase:Y87G2A.3b};
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, BIOPHYSICOCHEMICAL PROPERTIES, SUBCELLULAR
RP LOCATION, DEVELOPMENTAL STAGE, AND MUTAGENESIS OF HIS-129;
RP 167-GLN--ALA-481; 187-GLN--ALA-481; GLY-293; ALA-298; 374-TRP--ALA-481 AND
RP 412-GLN--ALA-481.
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 167-GLN--ALA-481.
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 (PubMed:22767594).
CC Exposure of the glycine at the C-terminus is essential for ATG8
CC proteins conjugation to phosphatidylethanolamine (PE) and insertion to
CC membranes, which is necessary for autophagy (Probable). Its cleavage
CC activity is functionally redundant to atg-4.2, but it cleaves lgg-1
CC precursors more efficiently than atg-4.2 (Probable). Acts redundantly
CC with atg-4.2 to promote the lgg-1 delipidation to release the protein
CC from membranes, which facilitates multiple events during macroautophagy
CC (PubMed:22767594). Unlike atg-4.2 does not seem to be required for
CC autophagosome maturation (PubMed:30880001).
CC {ECO:0000269|PubMed:22767594, ECO:0000269|PubMed:30880001}.
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=18.97 uM for lgg-1 {ECO:0000269|PubMed:22767594};
CC -!- INTERACTION:
CC K8ESC5-2; Q09490: lgg-1; NbExp=3; IntAct=EBI-331850, EBI-325374;
CC K8ESC5-2; Q23536: lgg-2; NbExp=3; IntAct=EBI-331850, EBI-331856;
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000255,
CC ECO:0000255|RuleBase:RU363115, ECO:0000269|PubMed:22767594,
CC ECO:0000269|PubMed:30880001}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=b {ECO:0000312|WormBase:Y87G2A.3b};
CC IsoId=K8ESC5-1; Sequence=Displayed;
CC Name=a {ECO:0000312|WormBase:Y87G2A.3a};
CC IsoId=K8ESC5-2; Sequence=VSP_060429;
CC -!- DEVELOPMENTAL STAGE: Ubiquitously expressed in embryos.
CC {ECO:0000269|PubMed:22767594}.
CC -!- SIMILARITY: Belongs to the peptidase C54 family. {ECO:0000255,
CC ECO:0000255|RuleBase:RU363115}.
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DR EMBL; BX284601; CAB54483.2; -; Genomic_DNA.
DR EMBL; BX284601; CCO25637.1; -; Genomic_DNA.
DR RefSeq; NP_001263575.1; NM_001276646.1.
DR RefSeq; NP_493375.2; NM_060974.4.
DR AlphaFoldDB; K8ESC5; -.
DR SMR; K8ESC5; -.
DR DIP; DIP-26265N; -.
DR IntAct; K8ESC5; 3.
DR STRING; 6239.Y87G2A.3b; -.
DR MEROPS; C54.008; -.
DR EPD; K8ESC5; -.
DR PaxDb; K8ESC5; -.
DR PeptideAtlas; K8ESC5; -.
DR EnsemblMetazoa; Y87G2A.3a.1; Y87G2A.3a.1; WBGene00013595. [K8ESC5-2]
DR EnsemblMetazoa; Y87G2A.3b.1; Y87G2A.3b.1; WBGene00013595. [K8ESC5-1]
DR UCSC; Y87G2A.3; c. elegans.
DR WormBase; Y87G2A.3a; CE42796; WBGene00013595; atg-4.1. [K8ESC5-2]
DR WormBase; Y87G2A.3b; CE47833; WBGene00013595; atg-4.1. [K8ESC5-1]
DR eggNOG; KOG2674; Eukaryota.
DR GeneTree; ENSGT00530000063000; -.
DR HOGENOM; CLU_021259_0_1_1; -.
DR InParanoid; K8ESC5; -.
DR OMA; DIRTMAF; -.
DR OrthoDB; 431748at2759; -.
DR PhylomeDB; K8ESC5; -.
DR Reactome; R-CEL-1632852; Macroautophagy.
DR PRO; PR:K8ESC5; -.
DR Proteomes; UP000001940; Chromosome I.
DR Bgee; WBGene00013595; Expressed in pharyngeal muscle cell (C elegans) and 4 other tissues.
DR GO; GO:0005737; C:cytoplasm; IDA:WormBase.
DR GO; GO:0004197; F:cysteine-type endopeptidase activity; IDA:WormBase.
DR GO; GO:0035973; P:aggrephagy; IMP:WormBase.
DR GO; GO:0016485; P:protein processing; IDA:WormBase.
DR GO; GO:0015031; P:protein transport; IEA:UniProtKB-KW.
DR InterPro; IPR038765; Papain-like_cys_pep_sf.
DR InterPro; IPR005078; Peptidase_C54.
DR PANTHER; PTHR22624; PTHR22624; 1.
DR Pfam; PF03416; Peptidase_C54; 1.
DR SUPFAM; SSF54001; SSF54001; 1.
PE 1: Evidence at protein level;
KW Alternative splicing; Autophagy; Cytoplasm; Hydrolase; Protease;
KW Protein transport; Reference proteome; Thiol protease; Transport.
FT CHAIN 1..481
FT /note="Cysteine protease atg-4.1"
FT /id="PRO_0000448583"
FT REGION 462..481
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT ACT_SITE 112
FT /note="Nucleophile"
FT /evidence="ECO:0000250|UniProtKB:Q9Y4P1"
FT ACT_SITE 313
FT /evidence="ECO:0000250|UniProtKB:Q9Y4P1"
FT ACT_SITE 315
FT /evidence="ECO:0000250|UniProtKB:Q9Y4P1"
FT VAR_SEQ 1..27
FT /note="Missing (in isoform a)"
FT /evidence="ECO:0000305"
FT /id="VSP_060429"
FT MUTAGEN 129
FT /note="H->P: In bp504; defective degradation of pgl-1- and
FT sepa-1-containing protein aggregates in comma stage
FT embryos. Reduces cleavage, but does not impair lipidation
FT of lgg-1."
FT /evidence="ECO:0000269|PubMed:22767594"
FT MUTAGEN 167..481
FT /note="Missing: In bp501; defective degradation of pgl-1-,
FT pgl-3-, sqst-1- and sepa-1-containing protein aggregates in
FT comma stage embryos. Abolishes cleavage, but does not
FT impair lipidation of lgg-1. In a atg-4.2 tm3948 mutant
FT background, animals are viable, but do not lay viable eggs,
FT and mutant embryos do not contain lipidated lgg-1.
FT Degradation defect is rescued in an lgg-1 mutant background
FT containing cleaved lgg-1. lgg-1-containing protein
FT aggregates do not abnormally accumulate in neuronal cell
FT bodies of AIY interneurons."
FT /evidence="ECO:0000269|PubMed:22767594,
FT ECO:0000269|PubMed:30880001"
FT MUTAGEN 187..481
FT /note="Missing: In bp451; defective degradation of pgl-
FT 1- and sepa-1-containing protein aggregates in comma stage
FT embryos. Reduces cleavage, but does not impair lipidation
FT of lgg-1."
FT /evidence="ECO:0000269|PubMed:22767594"
FT MUTAGEN 293
FT /note="G->S: In bp418; defective degradation of pgl-1- and
FT sepa-1-containing protein aggregates in comma stage
FT embryos."
FT /evidence="ECO:0000269|PubMed:22767594"
FT MUTAGEN 298
FT /note="A->V: In bp321; defective degradation of pgl-1- and
FT sepa-1-containing protein aggregates in comma stage
FT embryos. Reduces cleavage, but does not impair lipidation
FT of lgg-1."
FT /evidence="ECO:0000269|PubMed:22767594"
FT MUTAGEN 374..481
FT /note="Missing: In bp482; defective degradation of pgl-
FT 1- and sepa-1-containing protein aggregates in comma stage
FT embryos."
FT /evidence="ECO:0000269|PubMed:22767594"
FT MUTAGEN 412..481
FT /note="Missing: In bp410; defective degradation of pgl-
FT 1- and sepa-1-containing protein aggregates in comma stage
FT embryos."
FT /evidence="ECO:0000269|PubMed:22767594"
SQ SEQUENCE 481 AA; 54929 MW; FB876BB362AC6AFE CRC64;
MLSILPLAYS NFSRILQYFE QLPVVDKMTE EILKQGVGIV ETSLTFEPPF CESFERISID
NFPIFALGKE ISKEDGIEAM KKYVTSRFWF TYRRDFSPIG GTGPSTDQGW GCMLRCAQML
LGEVLLRRHI GRHFEWDIEK TSEIYEKILQ MFFDEKDALY SIHQIAQMGV TEGKEVSKWF
GPNTAAQVMK KLTIFDDWSN IAVHVALDNI LVKEDAITMA TSYPSEDAVK LIMENGLVDK
NRLSLSPGNI IPEWRPLLLM IPLRLGLTTI NPCYLSAIQE FFKIPQCVGI IGGRPNHALY
FVGMSGSKLF YLDPHYCRPK TESTAKMYAE KDSTATTDDV GFSHLEELVP LPSQTADVYT
KMDDSTYHCQ MMLWIEYENV DPSLALAMFC ETRDEFENLC ETLQKTTLPA SQPPMFEFLQ
RRPKYLPKFE PYTGVSMKIE MKEFDDIGAA NVKIDDDFEV LDVHTEEEDA DEDNDDDVAN
A
