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 27-MAR-2024, entry version 248. 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="https://atlasgeneticsoncology.org/gene/40202/CTSB"; CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- 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 PDB; 8B4T; X-ray; 1.45 A; A=79-333. DR PDB; 8B5F; X-ray; 1.70 A; A=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 PDBsum; 8B4T; -. DR PDBsum; 8B5F; -. DR AlphaFoldDB; P07858; -. DR SMR; P07858; -. DR BioGRID; 107888; 221. DR ComplexPortal; CPX-98; Cathepsin-B - cystatin-A complex. DR DIP; DIP-42785N; -. DR IntAct; P07858; 61. 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 GlyCosmos; P07858; 2 sites, 2 glycans. DR GlyGen; P07858; 3 sites, 2 N-linked glycans (1 site), 1 O-linked glycan (1 site). DR iPTMnet; P07858; -. DR MetOSite; P07858; -. DR PhosphoSitePlus; P07858; -. DR SwissPalm; P07858; -. DR BioMuta; CTSB; -. DR DMDM; 68067549; -. DR CPTAC; CPTAC-186; -. DR CPTAC; CPTAC-187; -. DR EPD; P07858; -. DR jPOST; P07858; -. DR MassIVE; P07858; -. DR MaxQB; P07858; -. DR PaxDb; 9606-ENSP00000345672; -. DR PeptideAtlas; P07858; -. DR PRIDE; P07858; -. DR ProteomicsDB; 52029; -. DR Pumba; P07858; -. DR TopDownProteomics; P07858; -. DR ABCD; P07858; 1 sequenced antibody. DR Antibodypedia; 4373; 768 antibodies from 42 providers. DR DNASU; 1508; -. DR Ensembl; ENST00000345125.8; ENSP00000342070.3; ENSG00000164733.23. DR Ensembl; ENST00000353047.11; ENSP00000345672.5; ENSG00000164733.23. DR Ensembl; ENST00000526645.6; ENSP00000431518.2; ENSG00000164733.23. DR Ensembl; ENST00000527215.7; ENSP00000433379.3; ENSG00000164733.23. DR Ensembl; ENST00000527243.6; ENSP00000434725.2; ENSG00000164733.23. DR Ensembl; ENST00000528965.3; ENSP00000433929.2; ENSG00000164733.23. DR Ensembl; ENST00000530296.6; ENSP00000435074.2; ENSG00000164733.23. DR Ensembl; ENST00000530640.7; ENSP00000435105.1; ENSG00000164733.23. DR Ensembl; ENST00000531089.6; ENSP00000433215.1; ENSG00000164733.23. DR Ensembl; ENST00000531502.6; ENSP00000435886.2; ENSG00000164733.23. DR Ensembl; ENST00000532392.3; ENSP00000432408.2; ENSG00000164733.23. DR Ensembl; ENST00000532656.7; ENSP00000431143.2; ENSG00000164733.23. DR Ensembl; ENST00000533455.6; ENSP00000432244.1; ENSG00000164733.23. DR Ensembl; ENST00000534382.6; ENSP00000435260.2; ENSG00000164733.23. DR Ensembl; ENST00000534510.6; ENSP00000434217.1; ENSG00000164733.23. DR Ensembl; ENST00000646105.3; ENSP00000493857.2; ENSG00000285132.3. DR Ensembl; ENST00000646239.2; ENSP00000494729.2; ENSG00000285132.3. DR Ensembl; ENST00000676691.1; ENSP00000503608.1; ENSG00000164733.23. DR Ensembl; ENST00000676755.1; ENSP00000504226.1; ENSG00000164733.23. DR Ensembl; ENST00000676825.1; ENSP00000503006.1; ENSG00000164733.23. DR Ensembl; ENST00000676843.1; ENSP00000504659.1; ENSG00000164733.23. DR Ensembl; ENST00000676952.1; ENSP00000503909.1; ENSG00000164733.23. DR Ensembl; ENST00000677082.1; ENSP00000503652.1; ENSG00000164733.23. DR Ensembl; ENST00000677366.1; ENSP00000504161.1; ENSG00000164733.23. DR Ensembl; ENST00000677415.1; ENSP00000502963.1; ENSG00000164733.23. DR Ensembl; ENST00000677418.1; ENSP00000503174.1; ENSG00000164733.23. DR Ensembl; ENST00000677544.1; ENSP00000503078.1; ENSG00000164733.23. DR Ensembl; ENST00000677650.1; ENSP00000504797.1; ENSG00000164733.23. DR Ensembl; ENST00000677671.1; ENSP00000503578.1; ENSG00000164733.23. DR Ensembl; ENST00000677819.1; ENSP00000503435.1; ENSG00000164733.23. DR Ensembl; ENST00000677873.1; ENSP00000503052.1; ENSG00000164733.23. DR Ensembl; ENST00000678092.1; ENSP00000504638.1; ENSG00000164733.23. DR Ensembl; ENST00000678145.1; ENSP00000503674.1; ENSG00000164733.23. DR Ensembl; ENST00000678242.1; ENSP00000503280.1; ENSG00000164733.23. DR Ensembl; ENST00000678357.1; ENSP00000503513.1; ENSG00000164733.23. DR Ensembl; ENST00000678615.1; ENSP00000504336.1; ENSG00000164733.23. DR Ensembl; ENST00000678929.1; ENSP00000503487.1; ENSG00000164733.23. DR Ensembl; ENST00000679051.1; ENSP00000503858.1; ENSG00000164733.23. DR Ensembl; ENST00000679128.1; ENSP00000504480.1; ENSG00000164733.23. DR Ensembl; ENST00000679140.1; ENSP00000503300.1; ENSG00000164733.23. DR Ensembl; ENST00000710700.1; ENSP00000518417.1; ENSG00000285132.3. DR Ensembl; ENST00000710702.1; ENSP00000518418.1; ENSG00000285132.3. DR Ensembl; ENST00000710703.1; ENSP00000518419.1; ENSG00000285132.3. DR Ensembl; ENST00000710704.1; ENSP00000518420.1; ENSG00000285132.3. DR Ensembl; ENST00000710705.1; ENSP00000518421.1; ENSG00000285132.3. DR Ensembl; ENST00000710713.1; ENSP00000518426.1; ENSG00000285132.3. DR Ensembl; ENST00000710714.1; ENSP00000518427.1; ENSG00000285132.3. DR Ensembl; ENST00000710715.1; ENSP00000518428.1; ENSG00000285132.3. DR Ensembl; ENST00000710716.1; ENSP00000518429.1; ENSG00000285132.3. DR Ensembl; ENST00000710717.1; ENSP00000518430.1; ENSG00000285132.3. DR Ensembl; ENST00000710718.1; ENSP00000518431.1; ENSG00000285132.3. DR Ensembl; ENST00000710719.1; ENSP00000518432.1; ENSG00000285132.3. DR Ensembl; ENST00000710720.1; ENSP00000518433.1; ENSG00000285132.3. DR Ensembl; ENST00000710721.1; ENSP00000518434.1; ENSG00000285132.3. DR Ensembl; ENST00000710722.1; ENSP00000518435.1; ENSG00000285132.3. DR Ensembl; ENST00000710723.1; ENSP00000518436.1; ENSG00000285132.3. DR Ensembl; ENST00000710724.1; ENSP00000518437.1; ENSG00000285132.3. DR Ensembl; ENST00000710725.1; ENSP00000518438.1; ENSG00000285132.3. DR Ensembl; ENST00000710727.1; ENSP00000518440.1; ENSG00000285132.3. DR Ensembl; ENST00000710728.1; ENSP00000518441.1; ENSG00000285132.3. DR Ensembl; ENST00000710729.1; ENSP00000518442.1; ENSG00000285132.3. DR Ensembl; ENST00000710730.1; ENSP00000518443.1; ENSG00000285132.3. DR Ensembl; ENST00000710731.1; ENSP00000518444.1; ENSG00000285132.3. DR Ensembl; ENST00000710732.1; ENSP00000518445.1; ENSG00000285132.3. DR Ensembl; ENST00000710743.1; ENSP00000518448.1; ENSG00000285132.3. DR Ensembl; ENST00000710744.1; ENSP00000518449.1; ENSG00000285132.3. DR Ensembl; ENST00000710745.1; ENSP00000518450.1; ENSG00000285132.3. DR Ensembl; ENST00000710747.1; ENSP00000518452.1; ENSG00000285132.3. DR Ensembl; ENST00000710750.1; ENSP00000518455.1; ENSG00000285132.3. DR Ensembl; ENST00000710751.1; ENSP00000518456.1; ENSG00000285132.3. DR Ensembl; ENST00000710752.1; ENSP00000518457.1; ENSG00000285132.3. DR Ensembl; ENST00000710755.1; ENSP00000518460.1; ENSG00000285132.3. DR Ensembl; ENST00000710759.1; ENSP00000518464.1; ENSG00000285132.3. DR Ensembl; ENST00000710761.1; ENSP00000518466.1; ENSG00000285132.3. DR Ensembl; ENST00000710763.1; ENSP00000518468.1; ENSG00000285132.3. DR Ensembl; ENST00000710764.1; ENSP00000518469.1; ENSG00000285132.3. 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 AGR; HGNC:2527; -. 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; 808912at2759; -. 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 1169 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 97 other cell types or tissues. DR ExpressionAtlas; P07858; baseline and differential. 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: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 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. DR SWISS-2DPAGE; P07858; -. DR UCD-2DPAGE; P07858; -. DR Genevisible; P07858; HS. 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 //