ID   CATB_RAT                Reviewed;         339 AA.
AC   P00787;
DT   21-JUL-1986, integrated into UniProtKB/Swiss-Prot.
DT   01-OCT-1996, sequence version 2.
DT   27-MAR-2024, entry version 188.
DE   RecName: Full=Cathepsin B;
DE            EC=3.4.22.1 {ECO:0000269|PubMed:1639824};
DE   AltName: Full=Cathepsin B1;
DE   AltName: Full=RSG-2;
DE   Contains:
DE     RecName: Full=Cathepsin B light chain {ECO:0000303|PubMed:6574504};
DE   Contains:
DE     RecName: Full=Cathepsin B heavy chain {ECO:0000303|PubMed:6574504};
DE   Flags: Precursor;
GN   Name=Ctsb;
OS   Rattus norvegicus (Rat).
OC   Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC   Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC   Murinae; Rattus.
OX   NCBI_TaxID=10116;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [MRNA], SUBCELLULAR LOCATION, TISSUE SPECIFICITY, AND
RP   INDUCTION.
RC   STRAIN=Sprague-Dawley; TISSUE=Mammary gland;
RX   PubMed=8001549; DOI=10.1111/j.1432-1033.1994.tb20055.x;
RA   Guenette R.S., Mooibroek M., Wong K., Wong P., Tenniswood M.;
RT   "Cathepsin B, a cysteine protease implicated in metastatic progression, is
RT   also expressed during regression of the rat prostate and mammary glands.";
RL   Eur. J. Biochem. 226:311-321(1994).
RN   [2]
RP   NUCLEOTIDE SEQUENCE [MRNA] OF 69-339.
RX   PubMed=2986112; DOI=10.1073/pnas.82.8.2320;
RA   San Segundo B., Chan S.J., Steiner D.F.;
RT   "Identification of cDNA clones encoding a precursor of rat liver cathepsin
RT   B.";
RL   Proc. Natl. Acad. Sci. U.S.A. 82:2320-2324(1985).
RN   [3]
RP   PROTEIN SEQUENCE OF 80-126 AND 129-333, AND GLYCOSYLATION AT ASN-192.
RC   TISSUE=Liver;
RX   PubMed=6574504; DOI=10.1073/pnas.80.12.3666;
RA   Takio K., Towatari T., Katunuma N., Teller D.C., Titani K.;
RT   "Homology of amino acid sequences of rat liver cathepsins B and H with that
RT   of papain.";
RL   Proc. Natl. Acad. Sci. U.S.A. 80:3666-3670(1983).
RN   [4]
RP   PROTEIN SEQUENCE OF 246-263, AND IDENTIFICATION BY MASS SPECTROMETRY.
RC   STRAIN=Sprague-Dawley; TISSUE=Hippocampus, and Spinal cord;
RA   Lubec G., Afjehi-Sadat L., Chen W.-Q.;
RL   Submitted (JAN-2009) to UniProtKB.
RN   [5]
RP   PROTEOLYTIC PROCESSING, FUNCTION, AND CATALYTIC ACTIVITY.
RX   PubMed=1639824; DOI=10.1016/s0021-9258(19)49632-4;
RA   Rowan A.D., Mason P., Mach L., Mort J.S.;
RT   "Rat procathepsin B. Proteolytic processing to the mature form in vitro.";
RL   J. Biol. Chem. 267:15993-15999(1992).
RN   [6]
RP   X-RAY CRYSTALLOGRAPHY (2.2 ANGSTROMS), AND ACTIVE SITE.
RX   PubMed=7890671; DOI=10.1074/jbc.270.10.5527;
RA   Jia Z., Hasnain S., Hirama T., Lee X., Mort J.S., To R., Huber C.P.;
RT   "Crystal structures of recombinant rat cathepsin B and a cathepsin B-
RT   inhibitor complex. Implications for structure-based inhibitor design.";
RL   J. Biol. Chem. 270:5527-5533(1995).
RN   [7]
RP   X-RAY CRYSTALLOGRAPHY (2.8 ANGSTROMS) OF 18-339, AND ACTIVE SITE.
RX   PubMed=8740363; DOI=10.1016/s0969-2126(96)00046-9;
RA   Cygler M., Sivaraman J., Grochulski P., Coulombe R., Storer A.C.,
RA   Mort J.S.;
RT   "Structure of rat procathepsin B: model for inhibition of cysteine protease
RT   activity by the proregion.";
RL   Structure 4:405-416(1996).
CC   -!- FUNCTION: Thiol protease which is believed to participate in
CC       intracellular degradation and turnover of proteins (PubMed:1639824).
CC       Cleaves matrix extracellular phosphoglycoprotein MEPE (By similarity).
CC       Involved in the solubilization of cross-linked TG/thyroglobulin in the
CC       thyroid follicle lumen (By similarity). Has also been implicated in
CC       tumor invasion and metastasis (By similarity).
CC       {ECO:0000250|UniProtKB:P07858, ECO:0000250|UniProtKB:P10605,
CC       ECO:0000269|PubMed:1639824}.
CC   -!- CATALYTIC ACTIVITY:
CC       Reaction=Hydrolysis of proteins with broad specificity for peptide
CC         bonds. Preferentially cleaves -Arg-Arg-|-Xaa bonds in small molecule
CC         substrates (thus differing from cathepsin L). In addition to being an
CC         endopeptidase, shows peptidyl-dipeptidase activity, liberating C-
CC         terminal dipeptides.; EC=3.4.22.1;
CC         Evidence={ECO:0000269|PubMed:1639824};
CC   -!- SUBUNIT: Dimer of a heavy chain and a light chain cross-linked by a
CC       disulfide bond. Interacts with SRPX2. Directly interacts with SHKBP1.
CC       {ECO:0000250|UniProtKB:P07858}.
CC   -!- SUBCELLULAR LOCATION: Lysosome {ECO:0000269|PubMed:8001549}. Melanosome
CC       {ECO:0000250|UniProtKB:P07858}. Secreted, extracellular space
CC       {ECO:0000250|UniProtKB:A1E295}. Apical cell membrane
CC       {ECO:0000250|UniProtKB:P10605}; Peripheral membrane protein
CC       {ECO:0000250|UniProtKB:P10605}; Extracellular side
CC       {ECO:0000250|UniProtKB:P10605}. Note=Localizes to the lumen of thyroid
CC       follicles and to the apical membrane of thyroid epithelial cells.
CC       {ECO:0000250|UniProtKB:P10605}.
CC   -!- TISSUE SPECIFICITY: Expressed in the epithelial cells of the prostate
CC       and mammary gland. {ECO:0000269|PubMed:8001549}.
CC   -!- INDUCTION: Expression is low in the lactacting mammary gland but
CC       increases after weaning to a peak 4 days post weaning. Expression
CC       returns to baseline levels 6 days post weaning.
CC       {ECO:0000269|PubMed:8001549}.
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; X82396; CAA57792.1; -; mRNA.
DR   EMBL; M11305; AAA40993.1; -; mRNA.
DR   PIR; S51041; KHRTB.
DR   PDB; 1CPJ; X-ray; 2.20 A; A/B=74-333.
DR   PDB; 1CTE; X-ray; 2.10 A; A/B=80-333.
DR   PDB; 1MIR; X-ray; 2.80 A; A/B=18-339.
DR   PDB; 1THE; X-ray; 1.90 A; A/B=74-333.
DR   PDBsum; 1CPJ; -.
DR   PDBsum; 1CTE; -.
DR   PDBsum; 1MIR; -.
DR   PDBsum; 1THE; -.
DR   AlphaFoldDB; P00787; -.
DR   SMR; P00787; -.
DR   STRING; 10116.ENSRNOP00000014178; -.
DR   BindingDB; P00787; -.
DR   ChEMBL; CHEMBL2602; -.
DR   MEROPS; C01.060; -.
DR   GlyCosmos; P00787; 1 site, No reported glycans.
DR   GlyGen; P00787; 1 site.
DR   iPTMnet; P00787; -.
DR   PhosphoSitePlus; P00787; -.
DR   SwissPalm; P00787; -.
DR   jPOST; P00787; -.
DR   PaxDb; 10116-ENSRNOP00000014178; -.
DR   UCSC; RGD:621509; rat.
DR   AGR; RGD:621509; -.
DR   RGD; 621509; Ctsb.
DR   eggNOG; KOG1543; Eukaryota.
DR   InParanoid; P00787; -.
DR   PhylomeDB; P00787; -.
DR   BRENDA; 3.4.22.1; 5301.
DR   Reactome; R-RNO-1442490; Collagen degradation.
DR   Reactome; R-RNO-1679131; Trafficking and processing of endosomal TLR.
DR   Reactome; R-RNO-2022090; Assembly of collagen fibrils and other multimeric structures.
DR   Reactome; R-RNO-2132295; MHC class II antigen presentation.
DR   Reactome; R-RNO-6798695; Neutrophil degranulation.
DR   SABIO-RK; P00787; -.
DR   EvolutionaryTrace; P00787; -.
DR   PRO; PR:P00787; -.
DR   Proteomes; UP000002494; Unplaced.
DR   GO; GO:0016324; C:apical plasma membrane; IDA:RGD.
DR   GO; GO:0009986; C:cell surface; IDA:RGD.
DR   GO; GO:0009897; C:external side of plasma membrane; IDA:RGD.
DR   GO; GO:0005576; C:extracellular region; IDA:RGD.
DR   GO; GO:0005615; C:extracellular space; IDA:RGD.
DR   GO; GO:0005764; C:lysosome; ISO:RGD.
DR   GO; GO:0042470; C:melanosome; IEA:UniProtKB-SubCell.
DR   GO; GO:1904090; C:peptidase inhibitor complex; ISO:RGD.
DR   GO; GO:0048471; C:perinuclear region of cytoplasm; ISO:RGD.
DR   GO; GO:0042383; C:sarcolemma; IDA:RGD.
DR   GO; GO:0005518; F:collagen binding; ISO:RGD.
DR   GO; GO:0004197; F:cysteine-type endopeptidase activity; IDA:CAFA.
DR   GO; GO:0008234; F:cysteine-type peptidase activity; ISO:RGD.
DR   GO; GO:0004175; F:endopeptidase activity; IDA:RGD.
DR   GO; GO:0030984; F:kininogen binding; IPI:RGD.
DR   GO; GO:0008233; F:peptidase activity; ISO:RGD.
DR   GO; GO:0042277; F:peptide binding; IDA:RGD.
DR   GO; GO:0043621; F:protein self-association; IDA:RGD.
DR   GO; GO:0044877; F:protein-containing complex binding; IPI:RGD.
DR   GO; GO:0043394; F:proteoglycan binding; ISO:RGD.
DR   GO; GO:0006914; P:autophagy; IEP:RGD.
DR   GO; GO:0071260; P:cellular response to mechanical stimulus; IEP:RGD.
DR   GO; GO:0097067; P:cellular response to thyroid hormone stimulus; ISO:RGD.
DR   GO; GO:0030574; P:collagen catabolic process; ISO:RGD.
DR   GO; GO:0046697; P:decidualization; ISO:RGD.
DR   GO; GO:0030855; P:epithelial cell differentiation; ISO:RGD.
DR   GO; GO:0051402; P:neuron apoptotic process; IMP:RGD.
DR   GO; GO:0030163; P:protein catabolic process; IDA:RGD.
DR   GO; GO:0006508; P:proteolysis; IDA:CAFA.
DR   GO; GO:0051603; P:proteolysis involved in protein catabolic process; ISO:RGD.
DR   GO; GO:0014075; P:response to amine; IEP:RGD.
DR   GO; GO:0034097; P:response to cytokine; IEP:RGD.
DR   GO; GO:0071548; P:response to dexamethasone; IEP:RGD.
DR   GO; GO:0045471; P:response to ethanol; IEP:RGD.
DR   GO; GO:0009749; P:response to glucose; IEP:RGD.
DR   GO; GO:0070670; P:response to interleukin-4; IEP:RGD.
DR   GO; GO:0009612; P:response to mechanical stimulus; IEP:RGD.
DR   GO; GO:0014070; P:response to organic cyclic compound; IEP:RGD.
DR   GO; GO:0043434; P:response to peptide hormone; IEP:RGD.
DR   GO; GO:0007519; P:skeletal muscle tissue development; IEP:RGD.
DR   GO; GO:0007283; P:spermatogenesis; IEP:RGD.
DR   GO; GO:0006590; P:thyroid hormone generation; ISO:RGD.
DR   GO; GO:0046718; P:viral entry into host cell; ISO:RGD.
DR   CDD; cd02620; Peptidase_C1A_CathepsinB; 1.
DR   Gene3D; 3.90.70.10; Cysteine proteinases; 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; IPR013128; Peptidase_C1A.
DR   InterPro; IPR000668; Peptidase_C1A_C.
DR   InterPro; IPR012599; Propeptide_C1A.
DR   PANTHER; PTHR12411:SF895; CATHEPSIN B; 1.
DR   PANTHER; PTHR12411; CYSTEINE PROTEASE FAMILY C1-RELATED; 1.
DR   Pfam; PF00112; Peptidase_C1; 1.
DR   Pfam; PF08127; Propeptide_C1; 1.
DR   PRINTS; PR00705; PAPAIN.
DR   SMART; SM00645; Pept_C1; 1.
DR   SUPFAM; SSF54001; Cysteine proteinases; 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   3D-structure; Acetylation; Cell membrane; Direct protein sequencing;
KW   Disulfide bond; Glycoprotein; Hydrolase; Lysosome; Membrane; Protease;
KW   Reference proteome; Secreted; Signal; Thiol protease; Zymogen.
FT   SIGNAL          1..17
FT                   /evidence="ECO:0000255"
FT   PROPEP          18..79
FT                   /note="Activation peptide"
FT                   /evidence="ECO:0000269|PubMed:1639824,
FT                   ECO:0000269|PubMed:6574504"
FT                   /id="PRO_0000026153"
FT   CHAIN           80..333
FT                   /note="Cathepsin B"
FT                   /id="PRO_0000026154"
FT   CHAIN           80..126
FT                   /note="Cathepsin B light chain"
FT                   /evidence="ECO:0000269|PubMed:6574504"
FT                   /id="PRO_0000026155"
FT   CHAIN           129..333
FT                   /note="Cathepsin B heavy chain"
FT                   /evidence="ECO:0000269|PubMed:6574504"
FT                   /id="PRO_0000026156"
FT   PROPEP          334..339
FT                   /evidence="ECO:0000250|UniProtKB:P07858"
FT                   /id="PRO_0000026157"
FT   ACT_SITE        108
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU10088,
FT                   ECO:0000269|PubMed:7890671, ECO:0000269|PubMed:8740363"
FT   ACT_SITE        278
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU10089,
FT                   ECO:0000269|PubMed:7890671, ECO:0000269|PubMed:8740363"
FT   ACT_SITE        298
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU10090,
FT                   ECO:0000269|PubMed:7890671, ECO:0000269|PubMed:8740363"
FT   MOD_RES         220
FT                   /note="N6-acetyllysine"
FT                   /evidence="ECO:0000250|UniProtKB:P10605"
FT   CARBOHYD        192
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000269|PubMed:6574504"
FT   DISULFID        93..122
FT                   /evidence="ECO:0000250|UniProtKB:P07858"
FT   DISULFID        105..150
FT                   /evidence="ECO:0000250|UniProtKB:P07858"
FT   DISULFID        141..207
FT                   /evidence="ECO:0000250|UniProtKB:P07858"
FT   DISULFID        142..146
FT                   /evidence="ECO:0000250|UniProtKB:P07858"
FT   DISULFID        179..211
FT                   /evidence="ECO:0000250|UniProtKB:P07858"
FT   DISULFID        187..198
FT                   /evidence="ECO:0000250|UniProtKB:P07858"
FT   VARIANT         302
FT                   /note="V -> A"
FT   CONFLICT        159
FT                   /note="W -> G (in Ref. 3; AA sequence)"
FT                   /evidence="ECO:0000305"
FT   HELIX           28..37
FT                   /evidence="ECO:0007829|PDB:1MIR"
FT   STRAND          40..43
FT                   /evidence="ECO:0007829|PDB:1MIR"
FT   HELIX           52..58
FT                   /evidence="ECO:0007829|PDB:1MIR"
FT   TURN            75..77
FT                   /evidence="ECO:0007829|PDB:1MIR"
FT   HELIX           86..89
FT                   /evidence="ECO:0007829|PDB:1THE"
FT   TURN            90..92
FT                   /evidence="ECO:0007829|PDB:1CPJ"
FT   TURN            94..97
FT                   /evidence="ECO:0007829|PDB:1THE"
FT   STRAND          104..106
FT                   /evidence="ECO:0007829|PDB:1CTE"
FT   HELIX           108..124
FT                   /evidence="ECO:0007829|PDB:1THE"
FT   TURN            125..127
FT                   /evidence="ECO:0007829|PDB:1THE"
FT   HELIX           135..141
FT                   /evidence="ECO:0007829|PDB:1THE"
FT   HELIX           144..146
FT                   /evidence="ECO:0007829|PDB:1THE"
FT   HELIX           149..151
FT                   /evidence="ECO:0007829|PDB:1THE"
FT   HELIX           155..164
FT                   /evidence="ECO:0007829|PDB:1THE"
FT   STRAND          178..180
FT                   /evidence="ECO:0007829|PDB:1THE"
FT   STRAND          188..191
FT                   /evidence="ECO:0007829|PDB:1THE"
FT   STRAND          193..195
FT                   /evidence="ECO:0007829|PDB:1THE"
FT   HELIX           220..222
FT                   /evidence="ECO:0007829|PDB:1THE"
FT   STRAND          226..232
FT                   /evidence="ECO:0007829|PDB:1THE"
FT   HELIX           236..246
FT                   /evidence="ECO:0007829|PDB:1THE"
FT   STRAND          249..256
FT                   /evidence="ECO:0007829|PDB:1THE"
FT   HELIX           257..259
FT                   /evidence="ECO:0007829|PDB:1THE"
FT   STRAND          264..267
FT                   /evidence="ECO:0007829|PDB:1THE"
FT   STRAND          274..288
FT                   /evidence="ECO:0007829|PDB:1THE"
FT   STRAND          291..297
FT                   /evidence="ECO:0007829|PDB:1THE"
FT   STRAND          309..313
FT                   /evidence="ECO:0007829|PDB:1THE"
FT   HELIX           318..320
FT                   /evidence="ECO:0007829|PDB:1THE"
FT   TURN            321..323
FT                   /evidence="ECO:0007829|PDB:1THE"
FT   STRAND          325..330
FT                   /evidence="ECO:0007829|PDB:1THE"
FT   HELIX           333..338
FT                   /evidence="ECO:0007829|PDB:1MIR"
SQ   SEQUENCE   339 AA;  37470 MW;  925E2E58C2B03CDA CRC64;
     MWWSLIPLSC LLALTSAHDK PSSHPLSDDM INYINKQNTT WQAGRNFYNV DISYLKKLCG
     TVLGGPNLPE RVGFSEDINL PESFDAREQW SNCPTIAQIR DQGSCGSCWA FGAVEAMSDR
     ICIHTNGRVN VEVSAEDLLT CCGIQCGDGC NGGYPSGAWN FWTRKGLVSG GVYNSHIGCL
     PYTIPPCEHH VNGSRPPCTG EGDTPKCNKM CEAGYSTSYK EDKHYGYTSY SVSDSEKEIM
     AEIYKNGPVE GAFTVFSDFL TYKSGVYKHE AGDVMGGHAI RILGWGIENG VPYWLVANSW
     NVDWGDNGFF KILRGENHCG IESEIVAGIP RTQQYWGRF
//