CATB_RAT
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 03-AUG-2022, entry version 182.
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 GlyGen; P00787; 1 site.
DR iPTMnet; P00787; -.
DR PhosphoSitePlus; P00787; -.
DR SwissPalm; P00787; -.
DR jPOST; P00787; -.
DR PaxDb; P00787; -.
DR PRIDE; P00787; -.
DR UCSC; RGD:621509; rat.
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:0005737; C:cytoplasm; 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; IDA:RGD.
DR GO; GO:0042470; C:melanosome; IEA:UniProtKB-SubCell.
DR GO; GO:0005739; C:mitochondrion; IDA:RGD.
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:0060548; P:negative regulation of cell death; IMP:RGD.
DR GO; GO:0010466; P:negative regulation of peptidase activity; ISO: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:0009611; P:response to wounding; 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 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; IPR012599; Propeptide_C1A.
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; 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 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
