CPR4_CAEEL
ID CPR4_CAEEL Reviewed; 335 AA.
AC P43508;
DT 01-NOV-1995, integrated into UniProtKB/Swiss-Prot.
DT 01-NOV-1995, sequence version 1.
DT 03-AUG-2022, entry version 155.
DE RecName: Full=Cathepsin B-like cysteine proteinase 4;
DE EC=3.4.22.-;
DE AltName: Full=Cysteine protease-related 4;
DE Flags: Precursor;
GN Name=cpr-4; ORFNames=F44C4.3;
OS Caenorhabditis elegans.
OC Eukaryota; Metazoa; Ecdysozoa; Nematoda; Chromadorea; Rhabditida;
OC Rhabditina; Rhabditomorpha; Rhabditoidea; Rhabditidae; Peloderinae;
OC Caenorhabditis.
OX NCBI_TaxID=6239;
RN [1]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA / MRNA].
RC STRAIN=Bristol N2;
RX PubMed=8561899; DOI=10.1089/dna.1996.15.75;
RA Larminie C.G.C., Johnstone I.L.;
RT "Isolation and characterization of four developmentally regulated cathepsin
RT B-like cysteine protease genes from the nematode Caenorhabditis elegans.";
RL DNA Cell Biol. 15:75-82(1996).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=Bristol N2;
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 [3]
RP FUNCTION, SUBCELLULAR LOCATION, DEVELOPMENTAL STAGE, INDUCTION, DISRUPTION
RP PHENOTYPE, ACTIVE SITES, MUTAGENESIS OF CYS-109; HIS-281 AND ASN-301, AND
RP IDENTIFICATION BY MASS SPECTROMETRY.
RX PubMed=28723894; DOI=10.1038/nature23284;
RA Peng Y., Zhang M., Zheng L., Liang Q., Li H., Chen J.T., Guo H.,
RA Yoshina S., Chen Y.Z., Zhao X., Wu X., Liu B., Mitani S., Yu J.S., Xue D.;
RT "Cysteine protease cathepsin B mediates radiation-induced bystander
RT effects.";
RL Nature 547:458-462(2017).
CC -!- FUNCTION: Thiol protease which shows activity against the fluorogenic
CC substrate z-Arg-Arg-AMC. {ECO:0000269|PubMed:28723894}.
CC -!- SUBCELLULAR LOCATION: Secreted {ECO:0000269|PubMed:28723894}.
CC Note=Secreted from animals irradiated with ultraviolet or ionizing
CC gamma rays into the culture medium. {ECO:0000269|PubMed:28723894}.
CC -!- DEVELOPMENTAL STAGE: Not detected in the embryo, observed in the
CC intestine of early stage L1-L3 larvae, peaks at the L4 larval stage and
CC declines in adulthood. {ECO:0000269|PubMed:28723894}.
CC -!- INDUCTION: Induced by ultraviolet and ionizing radiation through a cep-
CC 1-dependent mechanism. {ECO:0000269|PubMed:28723894}.
CC -!- DISRUPTION PHENOTYPE: RNAi-mediated knockdown results in greatly
CC reduced radiation-induced bystander effect (RIBE) activity in the
CC culture medium of irradiated animals. {ECO:0000269|PubMed:28723894}.
CC -!- MISCELLANEOUS: Mediates the radiation-induced bystander effect (RIBE),
CC a process in which factors released by irradiated cells or tissues
CC exert effects on unexposed cells or tissues. Following localized
CC ultraviolet irradiation of the head, mediates RIBE in multiple
CC unexposed regions including the posterior region. Also leads to RIBE
CC including inhibition of cell death and increased embryonic lethality of
CC progeny in unirradiated animals exposed to the culture medium of
CC irradiated animals. Likely to exert RIBE by acting through the insulin-
CC like receptor daf-2. {ECO:0000269|PubMed:28723894}.
CC -!- SIMILARITY: Belongs to the peptidase C1 family. {ECO:0000255|PROSITE-
CC ProRule:PRU10088, ECO:0000255|PROSITE-ProRule:PRU10089,
CC ECO:0000255|PROSITE-ProRule:PRU10090}.
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DR EMBL; L39895; AAA98785.1; -; mRNA.
DR EMBL; L39926; AAA98783.1; -; Genomic_DNA.
DR EMBL; FO081381; CCD71204.1; -; Genomic_DNA.
DR PIR; T37280; T37280.
DR RefSeq; NP_504682.1; NM_072281.5.
DR AlphaFoldDB; P43508; -.
DR SMR; P43508; -.
DR BioGRID; 44098; 9.
DR DIP; DIP-25376N; -.
DR IntAct; P43508; 1.
DR STRING; 6239.F44C4.3; -.
DR MEROPS; C01.A34; -.
DR EPD; P43508; -.
DR PaxDb; P43508; -.
DR PeptideAtlas; P43508; -.
DR EnsemblMetazoa; F44C4.3.1; F44C4.3.1; WBGene00000784.
DR GeneID; 179053; -.
DR KEGG; cel:CELE_F44C4.3; -.
DR UCSC; F44C4.3; c. elegans.
DR CTD; 179053; -.
DR WormBase; F44C4.3; CE07251; WBGene00000784; cpr-4.
DR eggNOG; KOG1543; Eukaryota.
DR GeneTree; ENSGT00970000196395; -.
DR HOGENOM; CLU_012184_3_3_1; -.
DR InParanoid; P43508; -.
DR OMA; YPINAWK; -.
DR OrthoDB; 865289at2759; -.
DR PhylomeDB; P43508; -.
DR BRENDA; 3.4.22.1; 1045.
DR PRO; PR:P43508; -.
DR Proteomes; UP000001940; Chromosome V.
DR Bgee; WBGene00000784; Expressed in adult organism and 4 other tissues.
DR GO; GO:0005576; C:extracellular region; IDA:UniProtKB.
DR GO; GO:0005615; C:extracellular space; IBA:GO_Central.
DR GO; GO:0005764; C:lysosome; IBA:GO_Central.
DR GO; GO:0004197; F:cysteine-type endopeptidase activity; IDA:UniProtKB.
DR GO; GO:0071480; P:cellular response to gamma radiation; IMP:UniProtKB.
DR GO; GO:0034644; P:cellular response to UV; IMP:UniProtKB.
DR GO; GO:0051603; P:proteolysis involved in protein catabolic process; IDA:UniProtKB.
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 Pfam; PF00112; Peptidase_C1; 1.
DR PRINTS; PR00705; PAPAIN.
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 Disulfide bond; Glycoprotein; Hydrolase; Protease; Reference proteome;
KW Secreted; Signal; Thiol protease; Zymogen.
FT SIGNAL 1..15
FT /evidence="ECO:0000255"
FT PROPEP 16..80
FT /evidence="ECO:0000255"
FT /id="PRO_0000026194"
FT CHAIN 81..335
FT /note="Cathepsin B-like cysteine proteinase 4"
FT /id="PRO_0000026195"
FT ACT_SITE 109
FT /evidence="ECO:0000269|PubMed:28723894"
FT ACT_SITE 281
FT /evidence="ECO:0000269|PubMed:28723894"
FT ACT_SITE 301
FT /evidence="ECO:0000250|UniProtKB:P07858"
FT CARBOHYD 193
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT DISULFID 94..123
FT /evidence="ECO:0000250|UniProtKB:P07858"
FT DISULFID 106..150
FT /evidence="ECO:0000250|UniProtKB:P07858"
FT DISULFID 142..209
FT /evidence="ECO:0000250|UniProtKB:P07858"
FT DISULFID 143..146
FT /evidence="ECO:0000250|UniProtKB:P07858"
FT DISULFID 179..213
FT /evidence="ECO:0000250|UniProtKB:P07858"
FT DISULFID 187..199
FT /evidence="ECO:0000250|UniProtKB:P07858"
FT MUTAGEN 109
FT /note="C->A: Loss of protease and RIBE activity."
FT /evidence="ECO:0000269|PubMed:28723894"
FT MUTAGEN 281
FT /note="H->A: Loss of protease and RIBE activity."
FT /evidence="ECO:0000269|PubMed:28723894"
FT MUTAGEN 301
FT /note="N->A: No effect on protease or RIBE activity."
FT /evidence="ECO:0000269|PubMed:28723894"
SQ SEQUENCE 335 AA; 36493 MW; 285900FAB876CED0 CRC64;
MKYLILAALV AVTAGLVIPL VPKTQEAITE YVNSKQSLWK AEIPKDITIE QVKKRLMRTE
FVAPHTPDVE VVKHDINEDT IPATFDARTQ WPNCMSINNI RDQSDCGSCW AFAAAEAASD
RFCIASNGAV NTLLSAEDVL SCCSNCGYGC EGGYPINAWK YLVKSGFCTG GSYEAQFGCK
PYSLAPCGET VGNVTWPSCP DDGYDTPACV NKCTNKNYNV AYTADKHFGS TAYAVGKKVS
QIQAEIIAHG PVEAAFTVYE DFYQYKTGVY VHTTGQELGG HAIRILGWGT DNGTPYWLVA
NSWNVNWGEN GYFRIIRGTN ECGIEHAVVG GVPKV
