CATB_HUMAN
ID CATB_HUMAN Reviewed; 339 AA.
AC P07858; B3KQR5; B3KRR5; Q503A6; Q96D87;
DT 01-AUG-1988, integrated into UniProtKB/Swiss-Prot.
DT 21-JUN-2005, sequence version 3.
DT 03-AUG-2022, entry version 239.
DE RecName: Full=Cathepsin B;
DE EC=3.4.22.1 {ECO:0000269|PubMed:12220505, ECO:0000269|PubMed:3972105};
DE AltName: Full=APP secretase;
DE Short=APPS;
DE AltName: Full=Cathepsin B1;
DE Contains:
DE RecName: Full=Cathepsin B light chain {ECO:0000303|PubMed:3972105};
DE Contains:
DE RecName: Full=Cathepsin B heavy chain {ECO:0000303|PubMed:3972105};
DE Flags: Precursor;
GN Name=CTSB; Synonyms=CPSB;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA], VARIANT VAL-26, AND GLYCOSYLATION AT ASN-192.
RX PubMed=3463996; DOI=10.1073/pnas.83.20.7721;
RA Chan S.J., San Segundo B., McCormick M.B., Steiner D.F.;
RT "Nucleotide and predicted amino acid sequences of cloned human and mouse
RT preprocathepsin B cDNAs.";
RL Proc. Natl. Acad. Sci. U.S.A. 83:7721-7725(1986).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC TISSUE=Gastric carcinoma;
RX PubMed=8112600; DOI=10.1016/0378-1119(94)90750-1;
RA Cao L., Taggart R.T., Berquin I.M., Moin K., Fong D., Sloane B.F.;
RT "Human gastric adenocarcinoma cathepsin B: isolation and sequencing of
RT full-length cDNAs and polymorphisms of the gene.";
RL Gene 139:163-169(1994).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA], AND VARIANT VAL-26.
RC TISSUE=Esophagus;
RX PubMed=14702039; DOI=10.1038/ng1285;
RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R.,
RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H.,
RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.,
RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K.,
RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H.,
RA Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M.,
RA Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K.,
RA Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T.,
RA Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M.,
RA Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S.,
RA Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H.,
RA Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K.,
RA Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N.,
RA Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S.,
RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O.,
RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H.,
RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B.,
RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y.,
RA Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K.,
RA Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T.,
RA Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T.,
RA Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y.,
RA Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H.,
RA Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y.,
RA Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H.,
RA Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O.,
RA Isogai T., Sugano S.;
RT "Complete sequencing and characterization of 21,243 full-length human
RT cDNAs.";
RL Nat. Genet. 36:40-45(2004).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RX PubMed=16303743; DOI=10.1093/dnares/12.2.117;
RA Otsuki T., Ota T., Nishikawa T., Hayashi K., Suzuki Y., Yamamoto J.,
RA Wakamatsu A., Kimura K., Sakamoto K., Hatano N., Kawai Y., Ishii S.,
RA Saito K., Kojima S., Sugiyama T., Ono T., Okano K., Yoshikawa Y.,
RA Aotsuka S., Sasaki N., Hattori A., Okumura K., Nagai K., Sugano S.,
RA Isogai T.;
RT "Signal sequence and keyword trap in silico for selection of full-length
RT human cDNAs encoding secretion or membrane proteins from oligo-capped cDNA
RT libraries.";
RL DNA Res. 12:117-126(2005).
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M.,
RA Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J.,
RA Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S.,
RA Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H.,
RA Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K.,
RA Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D.,
RA Hunkapiller M.W., Myers E.W., Venter J.C.;
RL Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases.
RN [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA], AND VARIANTS VAL-26 AND GLY-53.
RC TISSUE=Brain, and Placenta;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [7]
RP PROTEIN SEQUENCE OF 80-126 AND 129-333, FUNCTION, AND CATALYTIC ACTIVITY.
RC TISSUE=Liver;
RX PubMed=3972105; DOI=10.1016/0014-5793(85)81136-4;
RA Ritonja A., Popovic T., Turk V., Wiedenmann K., Machleidt W.;
RT "Amino acid sequence of human liver cathepsin B.";
RL FEBS Lett. 181:169-172(1985).
RN [8]
RP PROTEIN SEQUENCE OF 80-91 AND 129-139.
RC TISSUE=Liver;
RX PubMed=1637335; DOI=10.1042/bj2850427;
RA Moin K., Day N.A., Sameni M., Hasnain S., Hirama T., Sloane B.F.;
RT "Human tumour cathepsin B. Comparison with normal liver cathepsin B.";
RL Biochem. J. 285:427-434(1992).
RN [9]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 131-339.
RX PubMed=3010323; DOI=10.1073/pnas.83.9.2909;
RA Fong D., Calhoun D.H., Hsieh W.-T., Lee B., Wells R.D.;
RT "Isolation of a cDNA clone for the human lysosomal proteinase cathepsin
RT B.";
RL Proc. Natl. Acad. Sci. U.S.A. 83:2909-2913(1986).
RN [10]
RP FUNCTION, CATALYTIC ACTIVITY, AND ACTIVITY REGULATION.
RX PubMed=12220505; DOI=10.1016/s0006-291x(02)02125-3;
RA Guo R., Rowe P.S., Liu S., Simpson L.G., Xiao Z.S., Quarles L.D.;
RT "Inhibition of MEPE cleavage by Phex.";
RL Biochem. Biophys. Res. Commun. 297:38-45(2002).
RN [11]
RP SUBCELLULAR LOCATION [LARGE SCALE ANALYSIS].
RC TISSUE=Melanoma;
RX PubMed=12643545; DOI=10.1021/pr025562r;
RA Basrur V., Yang F., Kushimoto T., Higashimoto Y., Yasumoto K., Valencia J.,
RA Muller J., Vieira W.D., Watabe H., Shabanowitz J., Hearing V.J., Hunt D.F.,
RA Appella E.;
RT "Proteomic analysis of early melanosomes: identification of novel
RT melanosomal proteins.";
RL J. Proteome Res. 2:69-79(2003).
RN [12]
RP SUBCELLULAR LOCATION [LARGE SCALE ANALYSIS].
RC TISSUE=Melanoma;
RX PubMed=17081065; DOI=10.1021/pr060363j;
RA Chi A., Valencia J.C., Hu Z.-Z., Watabe H., Yamaguchi H., Mangini N.J.,
RA Huang H., Canfield V.A., Cheng K.C., Yang F., Abe R., Yamagishi S.,
RA Shabanowitz J., Hearing V.J., Wu C., Appella E., Hunt D.F.;
RT "Proteomic and bioinformatic characterization of the biogenesis and
RT function of melanosomes.";
RL J. Proteome Res. 5:3135-3144(2006).
RN [13]
RP INTERACTION WITH SHKBP1, AND SUBCELLULAR LOCATION.
RX PubMed=16733801; DOI=10.1007/s11010-006-9214-7;
RA Liu J.P., Liu N.S., Yuan H.Y., Guo Q., Lu H., Li Y.Y.;
RT "Human homologue of SETA binding protein 1 interacts with cathepsin B and
RT participates in TNF-Induced apoptosis in ovarian cancer cells.";
RL Mol. Cell. Biochem. 292:189-195(2006).
RN [14]
RP INTERACTION WITH SRPX2.
RX PubMed=18718938; DOI=10.1093/hmg/ddn256;
RA Royer-Zemmour B., Ponsole-Lenfant M., Gara H., Roll P., Leveque C.,
RA Massacrier A., Ferracci G., Cillario J., Robaglia-Schlupp A.,
RA Vincentelli R., Cau P., Szepetowski P.;
RT "Epileptic and developmental disorders of the speech cortex:
RT ligand/receptor interaction of wild-type and mutant SRPX2 with the
RT plasminogen activator receptor uPAR.";
RL Hum. Mol. Genet. 17:3617-3630(2008).
RN [15]
RP INVOLVEMENT IN KWE, AND TISSUE SPECIFICITY.
RX PubMed=28457472; DOI=10.1016/j.ajhg.2017.03.012;
RA Ngcungcu T., Oti M., Sitek J.C., Haukanes B.I., Linghu B., Bruccoleri R.,
RA Stokowy T., Oakeley E.J., Yang F., Zhu J., Sultan M., Schalkwijk J.,
RA van Vlijmen-Willems I.M.J.J., von der Lippe C., Brunner H.G., Ersland K.M.,
RA Grayson W., Buechmann-Moller S., Sundnes O., Nirmala N., Morgan T.M.,
RA van Bokhoven H., Steen V.M., Hull P.R., Szustakowski J., Staedtler F.,
RA Zhou H., Fiskerstrand T., Ramsay M.;
RT "Duplicated enhancer region increases expression of CTSB and segregates
RT with keratolytic winter erythema in South African and Norwegian families.";
RL Am. J. Hum. Genet. 100:737-750(2017).
RN [16]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=21269460; DOI=10.1186/1752-0509-5-17;
RA Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T.,
RA Bennett K.L., Superti-Furga G., Colinge J.;
RT "Initial characterization of the human central proteome.";
RL BMC Syst. Biol. 5:17-17(2011).
RN [17]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Liver;
RX PubMed=24275569; DOI=10.1016/j.jprot.2013.11.014;
RA Bian Y., Song C., Cheng K., Dong M., Wang F., Huang J., Sun D., Wang L.,
RA Ye M., Zou H.;
RT "An enzyme assisted RP-RPLC approach for in-depth analysis of human liver
RT phosphoproteome.";
RL J. Proteomics 96:253-262(2014).
RN [18]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=25944712; DOI=10.1002/pmic.201400617;
RA Vaca Jacome A.S., Rabilloud T., Schaeffer-Reiss C., Rompais M., Ayoub D.,
RA Lane L., Bairoch A., Van Dorsselaer A., Carapito C.;
RT "N-terminome analysis of the human mitochondrial proteome.";
RL Proteomics 15:2519-2524(2015).
RN [19]
RP X-RAY CRYSTALLOGRAPHY (2.15 ANGSTROMS), AND DISULFIDE BONDS.
RX PubMed=1868826; DOI=10.1002/j.1460-2075.1991.tb07771.x;
RA Musil D., Zucic D., Turk D., Engh R.A., Mayr I., Huber R., Popovic T.,
RA Turk V., Towatari T., Katunuma N., Bode W.;
RT "The refined 2.15 A X-ray crystal structure of human liver cathepsin B: the
RT structural basis for its specificity.";
RL EMBO J. 10:2321-2330(1991).
RN [20]
RP X-RAY CRYSTALLOGRAPHY (3.2 ANGSTROMS).
RX PubMed=8617355; DOI=10.1016/0014-5793(96)00309-2;
RA Turk D., Podobnik M., Kuhelj R., Dolinar M., Turk V.;
RT "Crystal structures of human procathepsin B at 3.2- and 3.3-A resolution
RT reveal an interaction motif between a papain-like cysteine protease and its
RT propeptide.";
RL FEBS Lett. 384:211-214(1996).
RN [21]
RP X-RAY CRYSTALLOGRAPHY (2.5 ANGSTROMS), AND ACTIVE SITE.
RX PubMed=9299326; DOI=10.1006/jmbi.1997.1218;
RA Podobnik M., Kuhelj R., Turk V., Turk D.;
RT "Crystal structure of the wild-type human procathepsin B at 2.5-A
RT resolution reveals the native active site of a papain-like cysteine
RT protease zymogen.";
RL J. Mol. Biol. 271:774-788(1997).
CC -!- FUNCTION: Thiol protease which is believed to participate in
CC intracellular degradation and turnover of proteins (PubMed:12220505).
CC Cleaves matrix extracellular phosphoglycoprotein MEPE
CC (PubMed:12220505). Involved in the solubilization of cross-linked
CC TG/thyroglobulin in the thyroid follicle lumen (By similarity). Has
CC also been implicated in tumor invasion and metastasis (PubMed:3972105).
CC {ECO:0000250|UniProtKB:P10605, ECO:0000269|PubMed:12220505,
CC ECO:0000269|PubMed:3972105}.
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:12220505, ECO:0000269|PubMed:3972105};
CC -!- ACTIVITY REGULATION: Inhibited by leupeptin.
CC {ECO:0000269|PubMed:12220505}.
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 (PubMed:16733801). {ECO:0000269|PubMed:16733801,
CC ECO:0000269|PubMed:18718938}.
CC -!- INTERACTION:
CC P07858; Q6UY14: ADAMTSL4; NbExp=3; IntAct=EBI-715062, EBI-742002;
CC P07858; P02760: AMBP; NbExp=4; IntAct=EBI-715062, EBI-2115136;
CC P07858; Q96IK1-2: BOD1; NbExp=3; IntAct=EBI-715062, EBI-18924329;
CC P07858; P40692: MLH1; NbExp=7; IntAct=EBI-715062, EBI-744248;
CC P07858; Q9NYA1: SPHK1; NbExp=4; IntAct=EBI-715062, EBI-985303;
CC -!- SUBCELLULAR LOCATION: Lysosome {ECO:0000269|PubMed:16733801}.
CC Melanosome {ECO:0000269|PubMed:17081065}. 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=Identified by mass spectrometry in
CC melanosome fractions from stage I to stage IV (PubMed:17081065).
CC Localizes to the lumen of thyroid follicles and to the apical membrane
CC of thyroid epithelial cells (By similarity).
CC {ECO:0000250|UniProtKB:P10605, ECO:0000269|PubMed:17081065}.
CC -!- TISSUE SPECIFICITY: Expressed in the stratum spinosum of the epidermis.
CC Weak expression is detected in the stratum granulosum.
CC {ECO:0000269|PubMed:28457472}.
CC -!- DISEASE: Keratolytic winter erythema (KWE) [MIM:148370]: An autosomal
CC dominant genodermatosis characterized by recurrent episodes of
CC palmoplantar erythema and epidermal peeling presenting seasonal
CC variation. KWE manifests during childhood. Skin lesions may spread to
CC the dorsum of hands and feet and to the interdigital spaces. Lower
CC legs, knees and thighs may also be involved. A less common finding is a
CC slowly migratory, annular erythema that is seen mostly on the
CC extremities. Between flares, the skin can appear unremarkable. Itching
CC can occur, and hyperhidrosis, associated with a pungent odor, is
CC invariably present. Formation of vesicles is rare, whereas keratolysis
CC that causes the formation of dry blisters is regularly seen. Cold
CC weather, moisture, febrile diseases, and physical and mental stress can
CC trigger exacerbations. In severely affected individuals, skin
CC manifestations persist unremittingly. Penetrance of the disease is
CC high, but expressivity is variable, even within the same family.
CC {ECO:0000269|PubMed:28457472}. Note=The gene represented in this entry
CC is involved in disease pathogenesis. Tandem duplications in a non-
CC coding genomic region containing an active enhancer element for CTSB
CC result in CTSB abnormal expression with pathological consequences.
CC {ECO:0000269|PubMed:28457472}.
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}.
CC -!- WEB RESOURCE: Name=Atlas of Genetics and Cytogenetics in Oncology and
CC Haematology;
CC URL="http://atlasgeneticsoncology.org/Genes/CTSBID40202ch8p23.html";
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DR EMBL; M14221; AAA52129.1; -; mRNA.
DR EMBL; L16510; AAC37547.1; -; mRNA.
DR EMBL; AK092070; BAG52477.1; -; mRNA.
DR EMBL; AK075393; BAG52127.1; -; mRNA.
DR EMBL; CH471157; EAW65630.1; -; Genomic_DNA.
DR EMBL; BC010240; AAH10240.1; -; mRNA.
DR EMBL; BC095408; AAH95408.1; -; mRNA.
DR EMBL; M13230; AAA52125.1; -; mRNA.
DR CCDS; CCDS5986.1; -.
DR PIR; A26498; KHHUB.
DR RefSeq; NP_001899.1; NM_001908.4.
DR RefSeq; NP_680090.1; NM_147780.3.
DR RefSeq; NP_680091.1; NM_147781.3.
DR RefSeq; NP_680092.1; NM_147782.3.
DR RefSeq; NP_680093.1; NM_147783.3.
DR RefSeq; XP_006716307.1; XM_006716244.2.
DR RefSeq; XP_006716308.1; XM_006716245.2.
DR RefSeq; XP_011542114.1; XM_011543812.2.
DR RefSeq; XP_016868586.1; XM_017013097.1.
DR RefSeq; XP_016868587.1; XM_017013098.1.
DR RefSeq; XP_016868588.1; XM_017013099.1.
DR RefSeq; XP_016868589.1; XM_017013100.1.
DR PDB; 1CSB; X-ray; 2.00 A; A/D=80-126, B/E=129-333.
DR PDB; 1GMY; X-ray; 1.90 A; A/B/C=79-339.
DR PDB; 1HUC; X-ray; 2.10 A; A/C=80-126, B/D=129-333.
DR PDB; 1PBH; X-ray; 3.20 A; A=18-333.
DR PDB; 2IPP; X-ray; 2.15 A; A=80-126, B=129-333.
DR PDB; 2PBH; X-ray; 3.30 A; A=18-333.
DR PDB; 3AI8; X-ray; 2.11 A; A/B=78-333.
DR PDB; 3CBJ; X-ray; 1.80 A; A=74-339.
DR PDB; 3CBK; X-ray; 2.67 A; A=74-339.
DR PDB; 3K9M; X-ray; 2.61 A; A/B=80-333.
DR PDB; 3PBH; X-ray; 2.50 A; A=18-333.
DR PDB; 5MBL; X-ray; 1.81 A; A=78-333.
DR PDB; 5MBM; X-ray; 2.76 A; A/B=78-333.
DR PDB; 6AY2; X-ray; 1.60 A; A/B=79-333.
DR PDBsum; 1CSB; -.
DR PDBsum; 1GMY; -.
DR PDBsum; 1HUC; -.
DR PDBsum; 1PBH; -.
DR PDBsum; 2IPP; -.
DR PDBsum; 2PBH; -.
DR PDBsum; 3AI8; -.
DR PDBsum; 3CBJ; -.
DR PDBsum; 3CBK; -.
DR PDBsum; 3K9M; -.
DR PDBsum; 3PBH; -.
DR PDBsum; 5MBL; -.
DR PDBsum; 5MBM; -.
DR PDBsum; 6AY2; -.
DR AlphaFoldDB; P07858; -.
DR SMR; P07858; -.
DR BioGRID; 107888; 195.
DR ComplexPortal; CPX-98; Cathepsin-B - cystatin-A complex.
DR DIP; DIP-42785N; -.
DR IntAct; P07858; 56.
DR MINT; P07858; -.
DR STRING; 9606.ENSP00000345672; -.
DR BindingDB; P07858; -.
DR ChEMBL; CHEMBL4072; -.
DR DrugBank; DB02108; 2-Aminoethanimidic Acid.
DR DrugBank; DB03329; 2-Pyridinethiol.
DR DrugBank; DB02148; 3-Amino-4-Oxybenzyl-2-Butanone.
DR DrugBank; DB02685; 3-Methylphenylalanine.
DR DrugBank; DB07219; BENZYL N-({(2S,3S)-3-[(PROPYLAMINO)CARBONYL]OXIRAN-2-YL}CARBONYL)-L-ISOLEUCYL-L-PROLINATE.
DR DrugBank; DB03588; Diphenylacetic acid.
DR DrugBank; DB07223; METHYL N-({(2S,3S)-3-[(PROPYLAMINO)CARBONYL]OXIRAN-2-YL}CARBONYL)-L-ISOLEUCYL-L-PROLINATE.
DR DrugBank; DB02855; N-(3-Propylcarbamoyloxirane-2-Carbonyl)-Isoleucyl-Proline.
DR DrugBank; DB07231; N-({(2S,3S)-3-[(BENZYLAMINO)CARBONYL]OXIRAN-2-YL}CARBONYL)-L-ISOLEUCYL-L-PROLINE.
DR DrugBank; DB04126; N-[1-Hydroxycarboxyethyl-Carbonyl]Leucylamino-2-Methyl-Butane.
DR DrugBank; DB04579; N-{[(2S,3S)-3-(Ethoxycarbonyl)-2-oxiranyl]carbonyl}-L-threonyl-L-isoleucine.
DR DrugBank; DB07160; N-{[(2S,3S)-3-(ETHOXYCARBONYL)OXIRAN-2-YL]CARBONYL}-L-ISOLEUCINE.
DR DrugBank; DB07224; N-{[(2S,3S)-3-(ETHOXYCARBONYL)OXIRAN-2-YL]CARBONYL}-L-ISOLEUCYL-L-ALANINE.
DR DrugBank; DB07225; N-{[(2S,3S)-3-(ETHOXYCARBONYL)OXIRAN-2-YL]CARBONYL}-L-ISOLEUCYL-L-ISOLEUCINE.
DR DrugBank; DB14962; Trastuzumab deruxtecan.
DR DrugCentral; P07858; -.
DR GuidetoPHARMACOLOGY; 2343; -.
DR MEROPS; C01.060; -.
DR GlyConnect; 2934; 1 N-Linked glycan (1 site).
DR GlyGen; P07858; 2 sites, 1 N-linked glycan (1 site).
DR iPTMnet; P07858; -.
DR MetOSite; P07858; -.
DR PhosphoSitePlus; P07858; -.
DR SwissPalm; P07858; -.
DR BioMuta; CTSB; -.
DR DMDM; 68067549; -.
DR SWISS-2DPAGE; P07858; -.
DR UCD-2DPAGE; P07858; -.
DR CPTAC; CPTAC-186; -.
DR CPTAC; CPTAC-187; -.
DR EPD; P07858; -.
DR jPOST; P07858; -.
DR MassIVE; P07858; -.
DR MaxQB; P07858; -.
DR PaxDb; P07858; -.
DR PeptideAtlas; P07858; -.
DR PRIDE; P07858; -.
DR ProteomicsDB; 52029; -.
DR TopDownProteomics; P07858; -.
DR ABCD; P07858; 1 sequenced antibody.
DR Antibodypedia; 4373; 684 antibodies from 42 providers.
DR DNASU; 1508; -.
DR Ensembl; ENST00000345125.8; ENSP00000342070.3; ENSG00000164733.22.
DR Ensembl; ENST00000353047.11; ENSP00000345672.5; ENSG00000164733.22.
DR Ensembl; ENST00000524654.2; ENSP00000432077.2; ENSG00000164733.22.
DR Ensembl; ENST00000526481.7; ENSP00000473301.2; ENSG00000164733.22.
DR Ensembl; ENST00000526645.6; ENSP00000431518.2; ENSG00000164733.22.
DR Ensembl; ENST00000527215.7; ENSP00000433379.3; ENSG00000164733.22.
DR Ensembl; ENST00000527243.6; ENSP00000434725.2; ENSG00000164733.22.
DR Ensembl; ENST00000528965.2; ENSP00000433929.2; ENSG00000164733.22.
DR Ensembl; ENST00000530296.6; ENSP00000435074.2; ENSG00000164733.22.
DR Ensembl; ENST00000530640.7; ENSP00000435105.1; ENSG00000164733.22.
DR Ensembl; ENST00000531089.6; ENSP00000433215.1; ENSG00000164733.22.
DR Ensembl; ENST00000531502.6; ENSP00000435886.2; ENSG00000164733.22.
DR Ensembl; ENST00000532392.2; ENSP00000432408.2; ENSG00000164733.22.
DR Ensembl; ENST00000532656.7; ENSP00000431143.2; ENSG00000164733.22.
DR Ensembl; ENST00000533455.6; ENSP00000432244.1; ENSG00000164733.22.
DR Ensembl; ENST00000534382.6; ENSP00000435260.2; ENSG00000164733.22.
DR Ensembl; ENST00000534510.6; ENSP00000434217.1; ENSG00000164733.22.
DR Ensembl; ENST00000676691.1; ENSP00000503608.1; ENSG00000164733.22.
DR Ensembl; ENST00000676755.1; ENSP00000504226.1; ENSG00000164733.22.
DR Ensembl; ENST00000676825.1; ENSP00000503006.1; ENSG00000164733.22.
DR Ensembl; ENST00000676843.1; ENSP00000504659.1; ENSG00000164733.22.
DR Ensembl; ENST00000676952.1; ENSP00000503909.1; ENSG00000164733.22.
DR Ensembl; ENST00000677082.1; ENSP00000503652.1; ENSG00000164733.22.
DR Ensembl; ENST00000677366.1; ENSP00000504161.1; ENSG00000164733.22.
DR Ensembl; ENST00000677415.1; ENSP00000502963.1; ENSG00000164733.22.
DR Ensembl; ENST00000677418.1; ENSP00000503174.1; ENSG00000164733.22.
DR Ensembl; ENST00000677544.1; ENSP00000503078.1; ENSG00000164733.22.
DR Ensembl; ENST00000677650.1; ENSP00000504797.1; ENSG00000164733.22.
DR Ensembl; ENST00000677671.1; ENSP00000503578.1; ENSG00000164733.22.
DR Ensembl; ENST00000677819.1; ENSP00000503435.1; ENSG00000164733.22.
DR Ensembl; ENST00000677873.1; ENSP00000503052.1; ENSG00000164733.22.
DR Ensembl; ENST00000678092.1; ENSP00000504638.1; ENSG00000164733.22.
DR Ensembl; ENST00000678145.1; ENSP00000503674.1; ENSG00000164733.22.
DR Ensembl; ENST00000678242.1; ENSP00000503280.1; ENSG00000164733.22.
DR Ensembl; ENST00000678357.1; ENSP00000503513.1; ENSG00000164733.22.
DR Ensembl; ENST00000678615.1; ENSP00000504336.1; ENSG00000164733.22.
DR Ensembl; ENST00000678929.1; ENSP00000503487.1; ENSG00000164733.22.
DR Ensembl; ENST00000679051.1; ENSP00000503858.1; ENSG00000164733.22.
DR Ensembl; ENST00000679128.1; ENSP00000504480.1; ENSG00000164733.22.
DR Ensembl; ENST00000679140.1; ENSP00000503300.1; ENSG00000164733.22.
DR GeneID; 1508; -.
DR KEGG; hsa:1508; -.
DR MANE-Select; ENST00000353047.11; ENSP00000345672.5; NM_001908.5; NP_001899.1.
DR UCSC; uc003wun.4; human.
DR CTD; 1508; -.
DR DisGeNET; 1508; -.
DR GeneCards; CTSB; -.
DR HGNC; HGNC:2527; CTSB.
DR HPA; ENSG00000164733; Low tissue specificity.
DR MalaCards; CTSB; -.
DR MIM; 116810; gene.
DR MIM; 148370; phenotype.
DR neXtProt; NX_P07858; -.
DR OpenTargets; ENSG00000164733; -.
DR Orphanet; 50943; Keratolytic winter erythema.
DR PharmGKB; PA27027; -.
DR VEuPathDB; HostDB:ENSG00000164733; -.
DR eggNOG; KOG1543; Eukaryota.
DR GeneTree; ENSGT00940000158680; -.
DR HOGENOM; CLU_012184_3_3_1; -.
DR InParanoid; P07858; -.
DR OMA; DEKIPYW; -.
DR OrthoDB; 865289at2759; -.
DR PhylomeDB; P07858; -.
DR TreeFam; TF314576; -.
DR BRENDA; 3.4.22.1; 2681.
DR PathwayCommons; P07858; -.
DR Reactome; R-HSA-1442490; Collagen degradation.
DR Reactome; R-HSA-1679131; Trafficking and processing of endosomal TLR.
DR Reactome; R-HSA-2022090; Assembly of collagen fibrils and other multimeric structures.
DR Reactome; R-HSA-2132295; MHC class II antigen presentation.
DR Reactome; R-HSA-6798695; Neutrophil degranulation.
DR SignaLink; P07858; -.
DR SIGNOR; P07858; -.
DR BioGRID-ORCS; 1508; 13 hits in 1090 CRISPR screens.
DR ChiTaRS; CTSB; human.
DR EvolutionaryTrace; P07858; -.
DR GeneWiki; Cathepsin_B; -.
DR GenomeRNAi; 1508; -.
DR Pharos; P07858; Tchem.
DR PRO; PR:P07858; -.
DR Proteomes; UP000005640; Chromosome 8.
DR RNAct; P07858; protein.
DR Bgee; ENSG00000164733; Expressed in stromal cell of endometrium and 95 other tissues.
DR ExpressionAtlas; P07858; baseline and differential.
DR Genevisible; P07858; HS.
DR GO; GO:0016324; C:apical plasma membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0062023; C:collagen-containing extracellular matrix; HDA:BHF-UCL.
DR GO; GO:0036021; C:endolysosome lumen; TAS:Reactome.
DR GO; GO:0009897; C:external side of plasma membrane; IEA:Ensembl.
DR GO; GO:0070062; C:extracellular exosome; HDA:UniProtKB.
DR GO; GO:0005576; C:extracellular region; TAS:Reactome.
DR GO; GO:0005615; C:extracellular space; IDA:BHF-UCL.
DR GO; GO:1904813; C:ficolin-1-rich granule lumen; TAS:Reactome.
DR GO; GO:0005764; C:lysosome; IDA:UniProtKB.
DR GO; GO:0042470; C:melanosome; IEA:UniProtKB-SubCell.
DR GO; GO:1904090; C:peptidase inhibitor complex; IPI:ComplexPortal.
DR GO; GO:0048471; C:perinuclear region of cytoplasm; IDA:UniProtKB.
DR GO; GO:0005518; F:collagen binding; IDA:BHF-UCL.
DR GO; GO:0004197; F:cysteine-type endopeptidase activity; IDA:BHF-UCL.
DR GO; GO:0008234; F:cysteine-type peptidase activity; IDA:UniProtKB.
DR GO; GO:0008233; F:peptidase activity; IDA:BHF-UCL.
DR GO; GO:0043394; F:proteoglycan binding; IPI:BHF-UCL.
DR GO; GO:0097067; P:cellular response to thyroid hormone stimulus; IEP:UniProtKB.
DR GO; GO:0030574; P:collagen catabolic process; IDA:BHF-UCL.
DR GO; GO:0046697; P:decidualization; IEA:Ensembl.
DR GO; GO:0030855; P:epithelial cell differentiation; IEP:UniProtKB.
DR GO; GO:0010466; P:negative regulation of peptidase activity; IDA:ComplexPortal.
DR GO; GO:0006508; P:proteolysis; IDA:UniProtKB.
DR GO; GO:0051603; P:proteolysis involved in protein catabolic process; IDA:BHF-UCL.
DR GO; GO:0042981; P:regulation of apoptotic process; TAS:UniProtKB.
DR GO; GO:0006590; P:thyroid hormone generation; IEA:Ensembl.
DR GO; GO:0046718; P:viral entry into host cell; IEA:Ensembl.
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:3972105"
FT /id="PRO_0000026143"
FT CHAIN 80..333
FT /note="Cathepsin B"
FT /id="PRO_0000026144"
FT CHAIN 80..126
FT /note="Cathepsin B light chain"
FT /evidence="ECO:0000269|PubMed:3972105"
FT /id="PRO_0000026145"
FT CHAIN 129..333
FT /note="Cathepsin B heavy chain"
FT /evidence="ECO:0000269|PubMed:3972105"
FT /id="PRO_0000026146"
FT PROPEP 334..339
FT /id="PRO_0000026147"
FT ACT_SITE 108
FT /evidence="ECO:0000269|PubMed:9299326"
FT ACT_SITE 278
FT /evidence="ECO:0000269|PubMed:9299326"
FT ACT_SITE 298
FT /evidence="ECO:0000269|PubMed:9299326"
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:3463996"
FT DISULFID 93..122
FT /evidence="ECO:0000269|PubMed:1868826"
FT DISULFID 105..150
FT /evidence="ECO:0000269|PubMed:1868826"
FT DISULFID 141..207
FT /evidence="ECO:0000269|PubMed:1868826"
FT DISULFID 142..146
FT /evidence="ECO:0000269|PubMed:1868826"
FT DISULFID 179..211
FT /evidence="ECO:0000269|PubMed:1868826"
FT DISULFID 187..198
FT /evidence="ECO:0000269|PubMed:1868826"
FT VARIANT 26
FT /note="L -> V (in dbSNP:rs12338)"
FT /evidence="ECO:0000269|PubMed:14702039,
FT ECO:0000269|PubMed:15489334, ECO:0000269|PubMed:3463996"
FT /id="VAR_006724"
FT VARIANT 53
FT /note="S -> G (in dbSNP:rs1803250)"
FT /evidence="ECO:0000269|PubMed:15489334"
FT /id="VAR_051511"
FT VARIANT 91
FT /note="P -> L (in dbSNP:rs11548596)"
FT /id="VAR_051512"
FT VARIANT 235
FT /note="S -> N (in dbSNP:rs17573)"
FT /id="VAR_014696"
FT CONFLICT 228
FT /note="N -> D (in Ref. 7; AA sequence)"
FT /evidence="ECO:0000305"
FT STRAND 20..22
FT /evidence="ECO:0007829|PDB:3PBH"
FT HELIX 28..37
FT /evidence="ECO:0007829|PDB:3PBH"
FT STRAND 40..43
FT /evidence="ECO:0007829|PDB:3PBH"
FT HELIX 52..57
FT /evidence="ECO:0007829|PDB:3PBH"
FT STRAND 69..72
FT /evidence="ECO:0007829|PDB:3PBH"
FT STRAND 82..85
FT /evidence="ECO:0007829|PDB:1GMY"
FT HELIX 86..89
FT /evidence="ECO:0007829|PDB:6AY2"
FT HELIX 94..97
FT /evidence="ECO:0007829|PDB:6AY2"
FT STRAND 104..106
FT /evidence="ECO:0007829|PDB:6AY2"
FT HELIX 108..124
FT /evidence="ECO:0007829|PDB:6AY2"
FT TURN 125..127
FT /evidence="ECO:0007829|PDB:6AY2"
FT STRAND 131..133
FT /evidence="ECO:0007829|PDB:3K9M"
FT HELIX 135..141
FT /evidence="ECO:0007829|PDB:6AY2"
FT HELIX 143..145
FT /evidence="ECO:0007829|PDB:6AY2"
FT HELIX 149..151
FT /evidence="ECO:0007829|PDB:1GMY"
FT HELIX 155..164
FT /evidence="ECO:0007829|PDB:6AY2"
FT STRAND 167..170
FT /evidence="ECO:0007829|PDB:3PBH"
FT TURN 173..175
FT /evidence="ECO:0007829|PDB:3CBK"
FT STRAND 178..180
FT /evidence="ECO:0007829|PDB:6AY2"
FT STRAND 188..191
FT /evidence="ECO:0007829|PDB:6AY2"
FT STRAND 193..195
FT /evidence="ECO:0007829|PDB:2IPP"
FT HELIX 220..222
FT /evidence="ECO:0007829|PDB:6AY2"
FT STRAND 226..231
FT /evidence="ECO:0007829|PDB:5MBL"
FT HELIX 236..246
FT /evidence="ECO:0007829|PDB:6AY2"
FT STRAND 249..256
FT /evidence="ECO:0007829|PDB:6AY2"
FT HELIX 259..261
FT /evidence="ECO:0007829|PDB:6AY2"
FT STRAND 264..267
FT /evidence="ECO:0007829|PDB:6AY2"
FT STRAND 274..288
FT /evidence="ECO:0007829|PDB:6AY2"
FT STRAND 291..297
FT /evidence="ECO:0007829|PDB:6AY2"
FT STRAND 302..304
FT /evidence="ECO:0007829|PDB:2IPP"
FT STRAND 309..313
FT /evidence="ECO:0007829|PDB:6AY2"
FT TURN 314..317
FT /evidence="ECO:0007829|PDB:5MBM"
FT HELIX 318..320
FT /evidence="ECO:0007829|PDB:6AY2"
FT TURN 321..323
FT /evidence="ECO:0007829|PDB:3CBJ"
FT STRAND 326..330
FT /evidence="ECO:0007829|PDB:5MBL"
SQ SEQUENCE 339 AA; 37822 MW; 0FC818EA4C1F6D90 CRC64;
MWQLWASLCC LLVLANARSR PSFHPLSDEL VNYVNKRNTT WQAGHNFYNV DMSYLKRLCG
TFLGGPKPPQ RVMFTEDLKL PASFDAREQW PQCPTIKEIR DQGSCGSCWA FGAVEAISDR
ICIHTNAHVS VEVSAEDLLT CCGSMCGDGC NGGYPAEAWN FWTRKGLVSG GLYESHVGCR
PYSIPPCEHH VNGSRPPCTG EGDTPKCSKI CEPGYSPTYK QDKHYGYNSY SVSNSEKDIM
AEIYKNGPVE GAFSVYSDFL LYKSGVYQHV TGEMMGGHAI RILGWGVENG TPYWLVANSW
NTDWGDNGFF KILRGQDHCG IESEVVAGIP RTDQYWEKI
