CPL1_CAEEL
ID CPL1_CAEEL Reviewed; 337 AA.
AC O45734; H9G333;
DT 05-JUN-2019, integrated into UniProtKB/Swiss-Prot.
DT 01-JUN-1998, sequence version 1.
DT 03-AUG-2022, entry version 172.
DE RecName: Full=Cathepsin L-like {ECO:0000303|PubMed:11707440};
DE EC=3.4.22.15 {ECO:0000250|UniProtKB:P06797};
DE Flags: Precursor;
GN Name=cpl-1 {ECO:0000303|PubMed:11707440, ECO:0000312|WormBase:T03E6.7a};
GN ORFNames=T03E6.7 {ECO:0000312|WormBase:T03E6.7a};
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, SUBCELLULAR LOCATION, TISSUE SPECIFICITY, DEVELOPMENTAL STAGE,
RP AND DISRUPTION PHENOTYPE.
RX PubMed=11707440; DOI=10.1074/jbc.m106117200;
RA Hashmi S., Britton C., Liu J., Guiliano D.B., Oksov Y., Lustigman S.;
RT "Cathepsin L is essential for embryogenesis and development of
RT Caenorhabditis elegans.";
RL J. Biol. Chem. 277:3477-3486(2002).
RN [3] {ECO:0000305}
RP FUNCTION, SUBCELLULAR LOCATION, DEVELOPMENTAL STAGE, AND MUTAGENESIS OF
RP 120-VAL--LYS-268.
RX PubMed=15456850; DOI=10.1242/jcs.01387;
RA Britton C., Murray L.;
RT "Cathepsin L protease (CPL-1) is essential for yolk processing during
RT embryogenesis in Caenorhabditis elegans.";
RL J. Cell Sci. 117:5133-5143(2004).
RN [4] {ECO:0000305}
RP SUBCELLULAR LOCATION, TISSUE SPECIFICITY, AND DEVELOPMENTAL STAGE.
RX PubMed=16857685; DOI=10.1074/jbc.m600254200;
RA Hashmi S., Zhang J., Oksov Y., Ji Q., Lustigman S.;
RT "The Caenorhabditis elegans CPI-2a cystatin-like inhibitor has an essential
RT regulatory role during oogenesis and fertilization.";
RL J. Biol. Chem. 281:28415-28429(2006).
RN [5] {ECO:0000305}
RP SUBCELLULAR LOCATION, AND MUTAGENESIS OF TRP-32 AND TYR-35.
RX PubMed=22768338; DOI=10.1371/journal.pone.0040145;
RA Miedel M.T., Graf N.J., Stephen K.E., Long O.S., Pak S.C., Perlmutter D.H.,
RA Silverman G.A., Luke C.J.;
RT "A pro-cathepsin L mutant is a luminal substrate for endoplasmic-reticulum-
RT associated degradation in C. elegans.";
RL PLoS ONE 7:E40145-E40145(2012).
RN [6] {ECO:0000305}
RP FUNCTION, SUBCELLULAR LOCATION, TISSUE SPECIFICITY, DEVELOPMENTAL STAGE,
RP AND MUTAGENESIS OF 1-MET--TYR-51; GLY-230 AND 120-VAL--LYS-268.
RX PubMed=24829385; DOI=10.1091/mbc.e14-01-0015;
RA Xu M., Liu Y., Zhao L., Gan Q., Wang X., Yang C.;
RT "The lysosomal cathepsin protease CPL-1 plays a leading role in phagosomal
RT degradation of apoptotic cells in Caenorhabditis elegans.";
RL Mol. Biol. Cell 25:2071-2083(2014).
RN [7] {ECO:0000305}
RP FUNCTION, AND MUTAGENESIS OF ALA-146 AND ARG-320.
RX PubMed=26773047; DOI=10.1534/genetics.115.179127;
RA Schmoekel V., Memar N., Wiekenberg A., Trotzmueller M., Schnabel R.,
RA Doering F.;
RT "Genetics of Lipid-Storage Management in Caenorhabditis elegans Embryos.";
RL Genetics 202:1071-1083(2016).
CC -!- FUNCTION: Cysteine protease which plays an essential role in the
CC degradation of proteins in lysosomes (PubMed:15456850,
CC PubMed:24829385). During early embryogenesis, maternally required for
CC the proteolytic processing of yolk proteins in platelets, a lysosome-
CC like structure where a slow and controlled degradation of yolk proteins
CC occurs (PubMed:15456850, PubMed:24829385). In the gonad, required for
CC the clearance of apoptotic germ cells in the engulfing cell
CC phagolysosomes (PubMed:24829385). In embryos, required for the
CC degradation of endocytic and autophagic cargos (PubMed:24829385). In
CC embryos, may play a role in the degradation of lipid-containing
CC droplets (PubMed:26773047). Required for larval development
CC (PubMed:11707440, PubMed:15456850). {ECO:0000269|PubMed:11707440,
CC ECO:0000269|PubMed:15456850, ECO:0000269|PubMed:24829385,
CC ECO:0000269|PubMed:26773047}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=Specificity close to that of papain. As compared to cathepsin
CC B, cathepsin L exhibits higher activity toward protein substrates,
CC but has little activity on Z-Arg-Arg-NHMec, and no peptidyl-
CC dipeptidase activity.; EC=3.4.22.15;
CC Evidence={ECO:0000250|UniProtKB:P06797};
CC -!- INTERACTION:
CC O45734; Q9U9Y8: lit-1; NbExp=2; IntAct=EBI-315958, EBI-318513;
CC -!- SUBCELLULAR LOCATION: Secreted {ECO:0000269|PubMed:11707440,
CC ECO:0000269|PubMed:15456850, ECO:0000269|PubMed:16857685}. Cytoplasmic
CC granule {ECO:0000269|PubMed:15456850, ECO:0000269|PubMed:16857685}.
CC Lysosome {ECO:0000269|PubMed:22768338, ECO:0000269|PubMed:24829385}.
CC Endosome {ECO:0000269|PubMed:22768338}. Cytoplasmic vesicle, phagosome
CC {ECO:0000269|PubMed:24829385}. Note=The zymogen form localizes to yolk
CC platelets/granules in the developing oocyte and in the pseudocoelom
CC (PubMed:15456850, PubMed:16857685). Following cell corpse phagocytosis,
CC recruited to phagosomes during the late stages of phagolysosome
CC formation (PubMed:24829385). {ECO:0000269|PubMed:15456850,
CC ECO:0000269|PubMed:16857685, ECO:0000269|PubMed:24829385}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=a {ECO:0000312|WormBase:T03E6.7a};
CC IsoId=O45734-1; Sequence=Displayed;
CC Name=b {ECO:0000312|WormBase:T03E6.7b};
CC IsoId=O45734-2; Sequence=VSP_060182;
CC -!- TISSUE SPECIFICITY: Expressed in intestine, pharynx posterior bulb,
CC hypodermis and cuticle (at protein level) (PubMed:11707440,
CC PubMed:24829385). Expressed in germ cells, developing oocytes, sheath
CC cells surrounding germ cells and oocytes, and in the eggshell (at
CC protein level) (PubMed:11707440, PubMed:16857685).
CC {ECO:0000269|PubMed:11707440, ECO:0000269|PubMed:16857685,
CC ECO:0000269|PubMed:24829385}.
CC -!- DEVELOPMENTAL STAGE: Expressed in embryos, larvae and adults (at
CC protein level) (PubMed:11707440, PubMed:15456850, PubMed:16857685,
CC PubMed:24829385). Expression transiently increases during early
CC embryonic stages and prior to the larval L1/L2, L2/L3, L3/L4 and
CC L4/adult molts (PubMed:11707440, PubMed:16857685). Highest expression
CC in adults (PubMed:11707440). In embryos, expressed in gut cells
CC (PubMed:11707440). In larvae, expressed in the hypodermis, intestine
CC and pharyngeal lining (PubMed:11707440). In molting larvae, expressed
CC in the old and new cuticle (PubMed:11707440).
CC {ECO:0000269|PubMed:11707440, ECO:0000269|PubMed:15456850,
CC ECO:0000269|PubMed:16857685, ECO:0000269|PubMed:24829385}.
CC -!- DISRUPTION PHENOTYPE: RNAi-mediated knockdown causes early embryonic
CC lethality with embryos arrested at the 100-200 cell stage
CC (PubMed:11707440). The few larvae which survive have incomplete gut
CC development and die at the L1 stage (PubMed:11707440). RNAi-mediated
CC knockdown at the L3 larval stage causes a growth delay, adults are
CC shorter and thinner, and lay fewer eggs (PubMed:11707440).
CC {ECO:0000269|PubMed:11707440}.
CC -!- SIMILARITY: Belongs to the peptidase C1 family. {ECO:0000255,
CC ECO:0000255|RuleBase:RU362133}.
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DR EMBL; BX284605; CAB07275.1; -; Genomic_DNA.
DR EMBL; BX284605; CCG28194.1; -; Genomic_DNA.
DR PIR; T24387; T24387.
DR RefSeq; NP_001256718.1; NM_001269789.1. [O45734-1]
DR RefSeq; NP_001256719.1; NM_001269790.1. [O45734-2]
DR AlphaFoldDB; O45734; -.
DR SMR; O45734; -.
DR DIP; DIP-26616N; -.
DR IntAct; O45734; 8.
DR MINT; O45734; -.
DR STRING; 6239.T03E6.7a; -.
DR MEROPS; C01.141; -.
DR EPD; O45734; -.
DR PaxDb; O45734; -.
DR PeptideAtlas; O45734; -.
DR EnsemblMetazoa; T03E6.7a.1; T03E6.7a.1; WBGene00000776. [O45734-1]
DR EnsemblMetazoa; T03E6.7b.1; T03E6.7b.1; WBGene00000776. [O45734-2]
DR GeneID; 180111; -.
DR KEGG; cel:CELE_T03E6.7; -.
DR UCSC; T03E6.7.1; c. elegans. [O45734-1]
DR CTD; 180111; -.
DR WormBase; T03E6.7a; CE16333; WBGene00000776; cpl-1. [O45734-1]
DR WormBase; T03E6.7b; CE47424; WBGene00000776; cpl-1. [O45734-2]
DR eggNOG; KOG1543; Eukaryota.
DR GeneTree; ENSGT00940000153321; -.
DR HOGENOM; CLU_012184_1_2_1; -.
DR InParanoid; O45734; -.
DR OMA; DNHWNLW; -.
DR OrthoDB; 1275401at2759; -.
DR PhylomeDB; O45734; -.
DR SignaLink; O45734; -.
DR PRO; PR:O45734; -.
DR Proteomes; UP000001940; Chromosome V.
DR Bgee; WBGene00000776; Expressed in adult organism and 4 other tissues.
DR GO; GO:0005737; C:cytoplasm; IDA:UniProtKB.
DR GO; GO:0036019; C:endolysosome; IDA:UniProtKB.
DR GO; GO:0005615; C:extracellular space; IDA:UniProtKB.
DR GO; GO:0005764; C:lysosome; IBA:GO_Central.
DR GO; GO:0032010; C:phagolysosome; IDA:UniProtKB.
DR GO; GO:0031983; C:vesicle lumen; IDA:WormBase.
DR GO; GO:0042718; C:yolk granule; IDA:UniProtKB.
DR GO; GO:0004197; F:cysteine-type endopeptidase activity; IBA:GO_Central.
DR GO; GO:0043277; P:apoptotic cell clearance; IMP:UniProtKB.
DR GO; GO:0006955; P:immune response; IBA:GO_Central.
DR GO; GO:1905691; P:lipid droplet disassembly; IMP:UniProtKB.
DR GO; GO:1903188; P:positive regulation of vitellogenesis; IMP:UniProtKB.
DR GO; GO:0051603; P:proteolysis involved in protein catabolic process; IBA:GO_Central.
DR GO; GO:0060785; P:regulation of apoptosis involved in tissue homeostasis; IMP:UniProtKB.
DR GO; GO:0070613; P:regulation of protein processing; IMP:UniProtKB.
DR CDD; cd02248; Peptidase_C1A; 1.
DR InterPro; IPR038765; Papain-like_cys_pep_sf.
DR InterPro; IPR025661; Pept_asp_AS.
DR InterPro; IPR000169; Pept_cys_AS.
DR InterPro; IPR025660; Pept_his_AS.
DR InterPro; IPR000668; Peptidase_C1A_C.
DR InterPro; IPR039417; Peptidase_C1A_papain-like.
DR InterPro; IPR013201; Prot_inhib_I29.
DR Pfam; PF08246; Inhibitor_I29; 1.
DR Pfam; PF00112; Peptidase_C1; 1.
DR PRINTS; PR00705; PAPAIN.
DR SMART; SM00848; Inhibitor_I29; 1.
DR SMART; SM00645; Pept_C1; 1.
DR SUPFAM; SSF54001; SSF54001; 1.
DR PROSITE; PS00640; THIOL_PROTEASE_ASN; 1.
DR PROSITE; PS00139; THIOL_PROTEASE_CYS; 1.
DR PROSITE; PS00639; THIOL_PROTEASE_HIS; 1.
PE 1: Evidence at protein level;
KW Alternative splicing; Cytoplasmic vesicle; Disulfide bond; Endosome;
KW Glycoprotein; Hydrolase; Lysosome; Protease; Reference proteome; Secreted;
KW Signal; Thiol protease; Zymogen.
FT SIGNAL 1..18
FT /evidence="ECO:0000255"
FT PROPEP 19..119
FT /note="Activation peptide"
FT /evidence="ECO:0000250|UniProtKB:P07711"
FT /id="PRO_0000447317"
FT CHAIN 120..337
FT /note="Cathepsin L-like"
FT /evidence="ECO:0000255"
FT /id="PRO_5005399912"
FT ACT_SITE 144
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU10088"
FT ACT_SITE 283
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU10089"
FT ACT_SITE 304
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU10090"
FT CARBOHYD 108
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00498"
FT DISULFID 141..184
FT /evidence="ECO:0000250|UniProtKB:O17473"
FT DISULFID 175..217
FT /evidence="ECO:0000250|UniProtKB:O17473"
FT DISULFID 276..326
FT /evidence="ECO:0000250|UniProtKB:O17473"
FT VAR_SEQ 1..139
FT /note="Missing (in isoform b)"
FT /evidence="ECO:0000305"
FT /id="VSP_060182"
FT MUTAGEN 1..51
FT /note="Missing: In qx304; temperature sensitive. At the
FT restrictive temperature of 25 degrees Celsius, causes an
FT accumulation of germ cell corpses in the gonad in an age-
FT dependent manner. In embryos, accumulation of abnormally
FT processed yolk proteins, and of endocytic and autophagic
FT cargos. Does not affect lysosomal localization."
FT /evidence="ECO:0000269|PubMed:24829385"
FT MUTAGEN 32
FT /note="W->A: Probably causes cpl-1 misfolding resulting in
FT its accumulation within the ER and loss of endolysosome
FT localization; when associated with A-35."
FT /evidence="ECO:0000269|PubMed:22768338"
FT MUTAGEN 35
FT /note="Y->A: Probably causes cpl-1 misfolding resulting in
FT its accumulation within the ER and loss of endolysosome
FT localization; when associated with A-32."
FT /evidence="ECO:0000269|PubMed:22768338"
FT MUTAGEN 120..268
FT /note="Missing: In ok360; 25 percent of F1 progeny die at
FT the embryonic stage. Embryos are arrested at the 100-150
FT cell stage and fail to undergo morphogenesis. Accumulation
FT of abnormally processed yolk proteins in large cytoplasmic
FT vesicles and delay in the degradation/recycling of the yolk
FT protein receptor rme-2. In the gonad, fails to eliminate
FT germ cell corpses in an age-dependent manner."
FT /evidence="ECO:0000269|PubMed:15456850,
FT ECO:0000269|PubMed:24829385"
FT MUTAGEN 146
FT /note="A->V: In t3438; temperature sensitive. Embryonic
FT lethal at the restrictive temperature of 25 degrees
FT Celsius. In oocytes and embryos, causes an intracellular
FT accumulation of enlarged neutral lipid-containing
FT droplets."
FT /evidence="ECO:0000269|PubMed:26773047"
FT MUTAGEN 230
FT /note="G->R: In yq89; temperature sensitive. At the
FT restrictive temperature of 25 degrees Celsius, causes an
FT accumulation of germ cell corpses in the gonad in an age-
FT dependent manner. Accumulation of abnormally processed yolk
FT proteins. Does not affect lysosomal localization."
FT /evidence="ECO:0000269|PubMed:24829385"
FT MUTAGEN 320
FT /note="R->C: In t3423; temperature sensitive. Embryonic
FT lethal at the restrictive temperature of 25 degrees
FT Celsius. In oocytes and embryos, causes an intracellular
FT accumulation of enlarged neutral lipid-containing
FT droplets."
FT /evidence="ECO:0000269|PubMed:26773047"
SQ SEQUENCE 337 AA; 38117 MW; F5754DED0745EE26 CRC64;
MNRFILLALV AAVVAVNSAK LSRQIESAIE KWDDYKEDFD KEYSESEEQT YMEAFVKNMI
HIENHNRDHR LGRKTFEMGL NHIADLPFSQ YRKLNGYRRL FGDSRIKNSS SFLAPFNVQV
PDEVDWRDTH LVTDVKNQGM CGSCWAFSAT GALEGQHARK LGQLVSLSEQ NLVDCSTKYG
NHGCNGGLMD QAFEYIRDNH GVDTEESYPY KGRDMKCHFN KKTVGADDKG YVDTPEGDEE
QLKIAVATQG PISIAIDAGH RSFQLYKKGV YYDEECSSEE LDHGVLLVGY GTDPEHGDYW
IVKNSWGAGW GEKGYIRIAR NRNNHCGVAT KASYPLV
