ID CATK_HUMAN Reviewed; 329 AA. AC P43235; Q6FHS6; DT 01-NOV-1995, integrated into UniProtKB/Swiss-Prot. DT 01-NOV-1995, sequence version 1. DT 02-OCT-2024, entry version 220. DE RecName: Full=Cathepsin K; DE EC=3.4.22.38; DE AltName: Full=Cathepsin O; DE AltName: Full=Cathepsin O2; DE AltName: Full=Cathepsin X; DE Flags: Precursor; GN Name=CTSK; Synonyms=CTSO, CTSO2; 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]. RC TISSUE=Blood; RX PubMed=7805878; DOI=10.1016/0014-5793(94)01349-6; RA Shi G.-P., Chapman H.A., Bhairi S.M., Deleeuw C., Reddy V.Y., Weiss S.J.; RT "Molecular cloning of human cathepsin O, a novel endoproteinase and RT homologue of rabbit OC2."; RL FEBS Lett. 357:129-134(1995). RN [2] RP NUCLEOTIDE SEQUENCE [MRNA], AND TISSUE SPECIFICITY. RC TISSUE=Bone; RX PubMed=7818555; DOI=10.1006/bbrc.1995.1013; RA Inaoka T., Bilbe G., Ishibashi O., Tezuka K., Kumegawa M., Kokubo T.; RT "Molecular cloning of human cDNA for cathepsin K: novel cysteine proteinase RT predominantly expressed in bone."; RL Biochem. Biophys. Res. Commun. 206:89-96(1995). RN [3] RP NUCLEOTIDE SEQUENCE [MRNA]. RC TISSUE=Osteoclastoma; RX PubMed=8585423; DOI=10.1002/jbmr.5650100809; RA Li Y., Alexander M., Wucherpfennig A.L., Yelick P., Chen W., Stashenko P.; RT "Cloning and complete coding sequence of a novel human cathepsin expressed RT in giant cells of osteoclastomas."; RL J. Bone Miner. Res. 10:1197-1202(1995). RN [4] RP NUCLEOTIDE SEQUENCE [MRNA]. RC TISSUE=Spleen; RX PubMed=7576232; DOI=10.1515/bchm3.1995.376.6.379; RA Broemme D., Okamoto K.; RT "Human cathepsin O2, a novel cysteine protease highly expressed in RT osteoclastomas and ovary molecular cloning, sequencing and tissue RT distribution."; RL Biol. Chem. Hoppe-Seyler 376:379-384(1995). RN [5] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. RA Ebert L., Schick M., Neubert P., Schatten R., Henze S., Korn B.; RT "Cloning of human full open reading frames in Gateway(TM) system entry RT vector (pDONR201)."; RL Submitted (JUN-2004) to the EMBL/GenBank/DDBJ databases. RN [6] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RX PubMed=16710414; DOI=10.1038/nature04727; RA Gregory S.G., Barlow K.F., McLay K.E., Kaul R., Swarbreck D., Dunham A., RA Scott C.E., Howe K.L., Woodfine K., Spencer C.C.A., Jones M.C., Gillson C., RA Searle S., Zhou Y., Kokocinski F., McDonald L., Evans R., Phillips K., RA Atkinson A., Cooper R., Jones C., Hall R.E., Andrews T.D., Lloyd C., RA Ainscough R., Almeida J.P., Ambrose K.D., Anderson F., Andrew R.W., RA Ashwell R.I.S., Aubin K., Babbage A.K., Bagguley C.L., Bailey J., RA Beasley H., Bethel G., Bird C.P., Bray-Allen S., Brown J.Y., Brown A.J., RA Buckley D., Burton J., Bye J., Carder C., Chapman J.C., Clark S.Y., RA Clarke G., Clee C., Cobley V., Collier R.E., Corby N., Coville G.J., RA Davies J., Deadman R., Dunn M., Earthrowl M., Ellington A.G., Errington H., RA Frankish A., Frankland J., French L., Garner P., Garnett J., Gay L., RA Ghori M.R.J., Gibson R., Gilby L.M., Gillett W., Glithero R.J., RA Grafham D.V., Griffiths C., Griffiths-Jones S., Grocock R., Hammond S., RA Harrison E.S.I., Hart E., Haugen E., Heath P.D., Holmes S., Holt K., RA Howden P.J., Hunt A.R., Hunt S.E., Hunter G., Isherwood J., James R., RA Johnson C., Johnson D., Joy A., Kay M., Kershaw J.K., Kibukawa M., RA Kimberley A.M., King A., Knights A.J., Lad H., Laird G., Lawlor S., RA Leongamornlert D.A., Lloyd D.M., Loveland J., Lovell J., Lush M.J., RA Lyne R., Martin S., Mashreghi-Mohammadi M., Matthews L., Matthews N.S.W., RA McLaren S., Milne S., Mistry S., Moore M.J.F., Nickerson T., O'Dell C.N., RA Oliver K., Palmeiri A., Palmer S.A., Parker A., Patel D., Pearce A.V., RA Peck A.I., Pelan S., Phelps K., Phillimore B.J., Plumb R., Rajan J., RA Raymond C., Rouse G., Saenphimmachak C., Sehra H.K., Sheridan E., RA Shownkeen R., Sims S., Skuce C.D., Smith M., Steward C., Subramanian S., RA Sycamore N., Tracey A., Tromans A., Van Helmond Z., Wall M., Wallis J.M., RA White S., Whitehead S.L., Wilkinson J.E., Willey D.L., Williams H., RA Wilming L., Wray P.W., Wu Z., Coulson A., Vaudin M., Sulston J.E., RA Durbin R.M., Hubbard T., Wooster R., Dunham I., Carter N.P., McVean G., RA Ross M.T., Harrow J., Olson M.V., Beck S., Rogers J., Bentley D.R.; RT "The DNA sequence and biological annotation of human chromosome 1."; RL Nature 441:315-321(2006). RN [7] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RA Mural R.J., Istrail S., Sutton 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 (SEP-2005) to the EMBL/GenBank/DDBJ databases. RN [8] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. RC TISSUE=Skin; 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 [9] RP FUNCTION, SUBCELLULAR LOCATION, AND TISSUE SPECIFICITY. RC TISSUE=Thyroid; RX PubMed=11082042; DOI=10.1242/jcs.113.24.4487; RA Tepel C., Broemme D., Herzog V., Brix K.; RT "Cathepsin K in thyroid epithelial cells: sequence, localization and RT possible function in extracellular proteolysis of thyroglobulin."; RL J. Cell Sci. 113:4487-4498(2000). RN [10] RP X-RAY CRYSTALLOGRAPHY (1.8 ANGSTROMS). RX PubMed=9033587; DOI=10.1038/nsb0297-105; RA McGrath M.E., Klaus J.L., Barnes M.G., Bromme D.; RT "Crystal structure of human cathepsin K complexed with a potent RT inhibitor."; RL Nat. Struct. Biol. 4:105-109(1997). RN [11] RP X-RAY CRYSTALLOGRAPHY (2.2 ANGSTROMS). RX PubMed=9405598; DOI=10.1073/pnas.94.26.14249; RA Thompson S.K., Halbert S.M., Bossard M.J., Tomaszek T.A., Levy M.A., RA Zhao B., Smith W.W., Abdel-Meguid S.S., Janson C.A., D'Alessio K.J., RA McQueney M.S., Amegadzie B.Y., Hanning C.R., Desjarlais R.L., Briand J., RA Sarkar S.K., Huddleston M.J., Ijames C.F., Carr S.A., Garnes K.T., Shu A., RA Heys J.R., Bradbeer J., Zembryki D., Veber D.F.; RT "Design of potent and selective human cathepsin K inhibitors that span the RT active site."; RL Proc. Natl. Acad. Sci. U.S.A. 94:14249-14254(1997). RN [12] RP X-RAY CRYSTALLOGRAPHY (2.8 ANGSTROMS) OF ZYMOGEN FORM. RX PubMed=9893980; DOI=10.1021/bi9822271; RA LaLonde J.M., Zhao B., Janson C.A., D'Alessio K.J., McQueney M.S., RA Orsini M.J., Debouck C.M., Smith W.W.; RT "The crystal structure of human procathepsin K."; RL Biochemistry 38:862-869(1999). RN [13] RP X-RAY CRYSTALLOGRAPHY (3.2 ANGSTROMS). RX PubMed=10048321; DOI=10.1110/ps.8.2.283; RA Sivaraman J., Lalumiere M., Menard R., Cygler M.; RT "Crystal structure of wild-type human procathepsin K."; RL Protein Sci. 8:283-290(1999). RN [14] RP VARIANT PKND ARG-146. RX PubMed=8703060; DOI=10.1126/science.273.5279.1236; RA Gelb B.D., Shi G.-P., Chapman H.A., Desnick R.J.; RT "Pycnodysostosis, a lysosomal disease caused by cathepsin K deficiency."; RL Science 273:1236-1238(1996). RN [15] RP VARIANT PKND VAL-277. RX PubMed=9529353; DOI=10.1086/301795; RA Gelb B.D., Willner J.P., Dunn T.M., Kardon N.B., Verloes A., Poncin J., RA Desnick R.J.; RT "Paternal uniparental disomy for chromosome 1 revealed by molecular RT analysis of a patient with pycnodysostosis."; RL Am. J. Hum. Genet. 62:848-854(1998). RN [16] RP VARIANT PKND GLU-79. RX PubMed=10491211; DOI=10.1359/jbmr.1999.14.10.1649; RA Ho N., Punturieri A., Wilkin D., Szabo J., Johnson M., Whaley J., Davis J., RA Clark A., Weiss S., Francomano C.; RT "Mutations of CTSK result in pycnodysostosis via a reduction in cathepsin K RT protein."; RL J. Bone Miner. Res. 14:1649-1653(1999). RN [17] RP VARIANTS PKND GLU-79 AND PRO-309. RX PubMed=10878663; DOI=10.1038/sj.ejhg.5200481; RA Haagerup A., Hertz J.M., Christensen M.F., Binderup H., Kruse T.A.; RT "Cathepsin K gene mutations and 1q21 haplotypes in at patients with RT pycnodysostosis in an outbred population."; RL Eur. J. Hum. Genet. 8:431-436(2000). RN [18] RP VARIANTS PKND PRO-122 AND VAL-277. RX PubMed=22822386; DOI=10.1159/000336581; RA Matsushita M., Kitoh H., Kaneko H., Mishima K., Itoh Y., Hattori T., RA Ishiguro N.; RT "Novel Compound Heterozygous Mutations in the Cathepsin K Gene in Japanese RT Female Siblings with Pyknodysostosis."; RL Mol. Syndromol. 2:254-258(2012). RN [19] RP VARIANT PKND CYS-283, AND CHARACTERIZATION OF VARIANT PKND CYS-283. RX PubMed=25731711; DOI=10.1177/0022034515573964; RA Xue Y., Wang L., Xia D., Li Q., Gao S., Dong M., Cai T., Shi S., He L., RA Hu K., Mao T., Duan X.; RT "Dental Abnormalities Caused by Novel Compound Heterozygous CTSK RT Mutations."; RL J. Dent. Res. 94:674-681(2015). CC -!- FUNCTION: Thiol protease involved in osteoclastic bone resorption and CC may participate partially in the disorder of bone remodeling. Displays CC potent endoprotease activity against fibrinogen at acid pH. May play an CC important role in extracellular matrix degradation. Involved in the CC release of thyroid hormone thyroxine (T4) by limited proteolysis of CC TG/thyroglobulin in the thyroid follicle lumen (PubMed:11082042). CC {ECO:0000269|PubMed:11082042}. CC -!- CATALYTIC ACTIVITY: CC Reaction=Broad proteolytic activity. With small-molecule substrates and CC inhibitors, the major determinant of specificity is P2, which is CC preferably Leu, Met > Phe, and not Arg.; EC=3.4.22.38; CC -!- SUBCELLULAR LOCATION: Lysosome {ECO:0000269|PubMed:11082042}. Secreted CC {ECO:0000269|PubMed:11082042}. Apical cell membrane CC {ECO:0000269|PubMed:11082042}; Peripheral membrane protein CC {ECO:0000269|PubMed:11082042}; Extracellular side CC {ECO:0000269|PubMed:11082042}. Note=Localizes to the lumen of thyroid CC follicles and to the apical membrane of thyroid epithelial cells. CC {ECO:0000269|PubMed:11082042}. CC -!- TISSUE SPECIFICITY: Predominantly expressed in osteoclasts (bones) CC (PubMed:7805878). Expressed in thyroid epithelial cells CC (PubMed:11082042). {ECO:0000269|PubMed:11082042, CC ECO:0000269|PubMed:7805878}. CC -!- DISEASE: Pycnodysostosis (PKND) [MIM:265800]: A rare autosomal CC recessive bone disorder characterized by deformity of the skull, CC maxilla and phalanges, osteosclerosis, and fragility of bone. CC {ECO:0000269|PubMed:10491211, ECO:0000269|PubMed:10878663, CC ECO:0000269|PubMed:22822386, ECO:0000269|PubMed:25731711, CC ECO:0000269|PubMed:8703060, ECO:0000269|PubMed:9529353}. Note=The CC disease is caused by variants affecting the gene represented in this CC entry. 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 --------------------------------------------------------------------------- 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; U13665; AAA65233.1; -; mRNA. DR EMBL; X82153; CAA57649.1; -; mRNA. DR EMBL; U20280; AAA95998.1; -; mRNA. DR EMBL; S79895; AAB35521.1; -; mRNA. DR EMBL; CR541675; CAG46476.1; -; mRNA. DR EMBL; AL355860; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; AL356292; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; CH471121; EAW53516.1; -; Genomic_DNA. DR EMBL; BC016058; AAH16058.1; -; mRNA. DR CCDS; CCDS969.1; -. DR PIR; JC2476; JC2476. DR RefSeq; NP_000387.1; NM_000396.3. DR PDB; 1ATK; X-ray; 2.20 A; A=115-329. DR PDB; 1AU0; X-ray; 2.60 A; A=115-329. DR PDB; 1AU2; X-ray; 2.60 A; A=115-329. DR PDB; 1AU3; X-ray; 2.50 A; A=115-329. DR PDB; 1AU4; X-ray; 2.30 A; A=115-329. DR PDB; 1AYU; X-ray; 2.20 A; A=115-329. DR PDB; 1AYV; X-ray; 2.30 A; A=115-329. DR PDB; 1AYW; X-ray; 2.40 A; A=115-329. DR PDB; 1BGO; X-ray; 2.30 A; A=115-329. DR PDB; 1BY8; X-ray; 2.60 A; A=16-329. DR PDB; 1MEM; X-ray; 1.80 A; A=115-329. DR PDB; 1NL6; X-ray; 2.80 A; A/B=115-329. DR PDB; 1NLJ; X-ray; 2.40 A; A/B=115-329. DR PDB; 1Q6K; X-ray; 2.10 A; A=115-329. DR PDB; 1SNK; X-ray; 2.40 A; A=116-329. DR PDB; 1TU6; X-ray; 1.75 A; A/B=115-329. DR PDB; 1U9V; X-ray; 2.20 A; A=113-329. DR PDB; 1U9W; X-ray; 2.30 A; A=113-329. DR PDB; 1U9X; X-ray; 2.10 A; A=113-329. DR PDB; 1VSN; X-ray; 2.00 A; A=115-329. DR PDB; 1YK7; X-ray; 2.50 A; A=115-329. DR PDB; 1YK8; X-ray; 2.60 A; A=115-329. DR PDB; 1YT7; X-ray; 2.30 A; A=115-329. DR PDB; 2ATO; X-ray; 2.00 A; A=115-329. DR PDB; 2AUX; X-ray; 2.40 A; A=115-329. DR PDB; 2AUZ; X-ray; 2.30 A; A=115-329. DR PDB; 2BDL; X-ray; 2.00 A; A=115-329. DR PDB; 2R6N; X-ray; 1.95 A; A=113-329. DR PDB; 3C9E; X-ray; 1.80 A; A=115-329. DR PDB; 3H7D; X-ray; 2.24 A; A/E=115-329. DR PDB; 3KW9; X-ray; 1.80 A; A=115-329. DR PDB; 3KWB; X-ray; 2.02 A; X/Y=115-329. DR PDB; 3KWZ; X-ray; 1.49 A; A=115-329. DR PDB; 3KX1; X-ray; 1.51 A; A=115-329. DR PDB; 3O0U; X-ray; 1.80 A; A=115-329. DR PDB; 3O1G; X-ray; 1.65 A; A=115-329. DR PDB; 3OVZ; X-ray; 2.02 A; A=121-329. DR PDB; 4DMX; X-ray; 1.70 A; A=115-329. DR PDB; 4DMY; X-ray; 1.63 A; A/B=115-329. DR PDB; 4N79; X-ray; 2.62 A; A=115-329. DR PDB; 4N8W; X-ray; 2.02 A; A=115-329. DR PDB; 4X6H; X-ray; 1.00 A; A=115-329. DR PDB; 4X6I; X-ray; 1.87 A; A=115-329. DR PDB; 4X6J; X-ray; 1.59 A; A=115-329. DR PDB; 4YV8; X-ray; 2.00 A; A=115-329. DR PDB; 4YVA; X-ray; 1.80 A; A=115-329. DR PDB; 5J94; X-ray; 2.60 A; A=107-329. DR PDB; 5JA7; X-ray; 1.61 A; A/B=107-329. DR PDB; 5JH3; X-ray; 1.75 A; A=107-329. DR PDB; 5TDI; X-ray; 1.40 A; A=115-329. DR PDB; 5TUN; X-ray; 1.62 A; A=115-329. DR PDB; 5Z5O; X-ray; 1.92 A; A=16-329, B=16-88. DR PDB; 6ASH; X-ray; 1.42 A; A=115-329. DR PDB; 6HGY; X-ray; 2.20 A; A=115-329. DR PDB; 6PXF; X-ray; 1.85 A; A=115-329. DR PDB; 6QBS; X-ray; 1.70 A; A/B=115-329. DR PDB; 6QL8; X-ray; 1.80 A; A=113-329. DR PDB; 6QLM; X-ray; 1.50 A; A/B=114-329. DR PDB; 6QLW; X-ray; 2.00 A; A/B/C/D=114-329. DR PDB; 6QLX; X-ray; 2.10 A; A=114-329. DR PDB; 6QM0; X-ray; 1.90 A; A/B=114-329. DR PDB; 7NXL; X-ray; 1.80 A; AAA=114-329. DR PDB; 7NXM; X-ray; 1.72 A; A=114-329. DR PDB; 7PCK; X-ray; 3.20 A; A/B/C/D=16-329. DR PDB; 7QBL; X-ray; 2.00 A; A=115-329. DR PDB; 7QBM; X-ray; 1.88 A; A/P=16-329. DR PDB; 7QBN; X-ray; 1.55 A; A=113-329. DR PDB; 7QBO; X-ray; 1.90 A; A/P=16-329. DR PDB; 8C3D; X-ray; 2.00 A; A=115-329. DR PDBsum; 1ATK; -. DR PDBsum; 1AU0; -. DR PDBsum; 1AU2; -. DR PDBsum; 1AU3; -. DR PDBsum; 1AU4; -. DR PDBsum; 1AYU; -. DR PDBsum; 1AYV; -. DR PDBsum; 1AYW; -. DR PDBsum; 1BGO; -. DR PDBsum; 1BY8; -. DR PDBsum; 1MEM; -. DR PDBsum; 1NL6; -. DR PDBsum; 1NLJ; -. DR PDBsum; 1Q6K; -. DR PDBsum; 1SNK; -. DR PDBsum; 1TU6; -. DR PDBsum; 1U9V; -. DR PDBsum; 1U9W; -. DR PDBsum; 1U9X; -. DR PDBsum; 1VSN; -. DR PDBsum; 1YK7; -. DR PDBsum; 1YK8; -. DR PDBsum; 1YT7; -. DR PDBsum; 2ATO; -. DR PDBsum; 2AUX; -. DR PDBsum; 2AUZ; -. DR PDBsum; 2BDL; -. DR PDBsum; 2R6N; -. DR PDBsum; 3C9E; -. DR PDBsum; 3H7D; -. DR PDBsum; 3KW9; -. DR PDBsum; 3KWB; -. DR PDBsum; 3KWZ; -. DR PDBsum; 3KX1; -. DR PDBsum; 3O0U; -. DR PDBsum; 3O1G; -. DR PDBsum; 3OVZ; -. DR PDBsum; 4DMX; -. DR PDBsum; 4DMY; -. DR PDBsum; 4N79; -. DR PDBsum; 4N8W; -. DR PDBsum; 4X6H; -. DR PDBsum; 4X6I; -. DR PDBsum; 4X6J; -. DR PDBsum; 4YV8; -. DR PDBsum; 4YVA; -. DR PDBsum; 5J94; -. DR PDBsum; 5JA7; -. DR PDBsum; 5JH3; -. DR PDBsum; 5TDI; -. DR PDBsum; 5TUN; -. DR PDBsum; 5Z5O; -. DR PDBsum; 6ASH; -. DR PDBsum; 6HGY; -. DR PDBsum; 6PXF; -. DR PDBsum; 6QBS; -. DR PDBsum; 6QL8; -. DR PDBsum; 6QLM; -. DR PDBsum; 6QLW; -. DR PDBsum; 6QLX; -. DR PDBsum; 6QM0; -. DR PDBsum; 7NXL; -. DR PDBsum; 7NXM; -. DR PDBsum; 7PCK; -. DR PDBsum; 7QBL; -. DR PDBsum; 7QBM; -. DR PDBsum; 7QBN; -. DR PDBsum; 7QBO; -. DR PDBsum; 8C3D; -. DR AlphaFoldDB; P43235; -. DR SMR; P43235; -. DR BioGRID; 107893; 16. DR DIP; DIP-39993N; -. DR IntAct; P43235; 11. DR STRING; 9606.ENSP00000271651; -. DR BindingDB; P43235; -. DR ChEMBL; CHEMBL268; -. DR DrugBank; DB08287; (1R,2R)-N-(2-Aminoethyl)-2-{[(4-methoxyphenyl)sulfonyl]methyl}cyclohexanecarboxamide. DR DrugBank; DB04244; (2R)-2-(3-Biphenylyl)-N-{(2R)-2-hydroxy-3-[(2-pyridinylsulfonyl)amino]propyl}-4-methylpentanamide. DR DrugBank; DB07592; (2R)-3-Methyl-1-phenyl-2-butanyl [(2S)-1-oxo-2-hexanyl]carbamate. DR DrugBank; DB07593; 1-(PHENYLMETHYL)CYCLOPENTYL[(1S)-1-FORMYLPENTYL]CARBAMATE. DR DrugBank; DB07563; 1-{7-cyclohexyl-6-[4-(4-methylpiperazin-1-yl)benzyl]-7H-pyrrolo[2,3-d]pyrimidin-2-yl}methanamine. DR DrugBank; DB02869; 3-amino-5-phenylpentane. DR DrugBank; DB07965; 6-(cyclohexylamino)-9-[2-(4-methylpiperazin-1-yl)-ethyl]-9H-purine-2-carbonitrile. DR DrugBank; DB07967; 9-CYCLOPENTYL-6-[2-(3-IMIDAZOL-1-YL-PROPOXY)-PHENYLAMINO]-9H-PURINE-2-CARBONITRILE. DR DrugBank; DB01858; [1-(4-Fluorobenzyl)Cyclobutyl]Methyl (1s)-1-[Oxo(1h-Pyrazol-5-Ylamino)Acetyl]Pentylcarbamate. DR DrugBank; DB12239; Balicatib. DR DrugBank; DB02679; Cyanamide. DR DrugBank; DB03891; Dibenzyl (carbonylbis{2,1-hydrazinediyl[(2S)-4-methyl-1-oxo-1,2-pentanediyl]})biscarbamate. DR DrugBank; DB05736; MIV-701. DR DrugBank; DB15599; MIV-711. DR DrugBank; DB08270; N-(2-AMINOETHYL)-N~2~-{(1S)-1-[4'-(AMINOSULFONYL)BIPHENYL-4-YL]-2,2,2-TRIFLUOROETHYL}-L-LEUCINAMIDE. DR DrugBank; DB03642; N-[(2S)-4-Methyl-1-oxo-1-{[(4S)-3-oxo-1-(2-pyridinylsulfonyl)-4-azepanyl]amino}-2-pentanyl]-1-benzofuran-2-carboxamide. DR DrugBank; DB04234; N2-({[(4-Bromophenyl)Methyl]Oxy}Carbonyl)-N1-[(1s)-1-Formylpentyl]-L-Leucinamide. DR DrugBank; DB03405; N2-[(Benzyloxy)carbonyl]-N-[(3R)-1-{N-[(benzyloxy)carbonyl]-L-leucyl}-4-oxo-3-pyrrolidinyl]-L-leucinamide. DR DrugBank; DB03456; N2-[(benzyloxy)carbonyl]-n1-[(3S)-1-cyanopyrrolidin-3-yl]-l-leucinamide. DR DrugBank; DB06670; Odanacatib. DR DrugBank; DB06367; Relacatib. DR DrugBank; DB08594; TERT-BUTYL 2-CYANO-2-METHYLHYDRAZINECARBOXYLATE. DR DrugBank; DB04523; Tert-Butyl(1s)-1-Cyclohexyl-2-Oxoethylcarbamate. DR DrugCentral; P43235; -. DR GuidetoPHARMACOLOGY; 2350; -. DR MEROPS; C01.036; -. DR MEROPS; I29.007; -. DR GlyCosmos; P43235; 1 site, No reported glycans. DR GlyGen; P43235; 1 site. DR iPTMnet; P43235; -. DR PhosphoSitePlus; P43235; -. DR BioMuta; CTSK; -. DR DMDM; 1168793; -. DR jPOST; P43235; -. DR MassIVE; P43235; -. DR PaxDb; 9606-ENSP00000271651; -. DR PeptideAtlas; P43235; -. DR ProteomicsDB; 55598; -. DR Antibodypedia; 34039; 640 antibodies from 37 providers. DR DNASU; 1513; -. DR Ensembl; ENST00000271651.8; ENSP00000271651.3; ENSG00000143387.14. DR Ensembl; ENST00000676824.1; ENSP00000504176.1; ENSG00000143387.14. DR Ensembl; ENST00000676966.1; ENSP00000503723.1; ENSG00000143387.14. DR GeneID; 1513; -. DR KEGG; hsa:1513; -. DR MANE-Select; ENST00000271651.8; ENSP00000271651.3; NM_000396.4; NP_000387.1. DR UCSC; uc001evp.3; human. DR AGR; HGNC:2536; -. DR CTD; 1513; -. DR DisGeNET; 1513; -. DR GeneCards; CTSK; -. DR GeneReviews; CTSK; -. DR HGNC; HGNC:2536; CTSK. DR HPA; ENSG00000143387; Tissue enhanced (cervix). DR MalaCards; CTSK; -. DR MIM; 265800; phenotype. DR MIM; 601105; gene. DR neXtProt; NX_P43235; -. DR OpenTargets; ENSG00000143387; -. DR Orphanet; 763; Pycnodysostosis. DR PharmGKB; PA27034; -. DR VEuPathDB; HostDB:ENSG00000143387; -. DR eggNOG; KOG1543; Eukaryota. DR GeneTree; ENSGT00940000157759; -. DR HOGENOM; CLU_012184_1_2_1; -. DR InParanoid; P43235; -. DR OMA; ETWGNKG; -. DR OrthoDB; 5472948at2759; -. DR PhylomeDB; P43235; -. DR TreeFam; TF313739; -. DR BRENDA; 3.4.22.38; 2681. DR PathwayCommons; P43235; -. DR Reactome; R-HSA-1442490; Collagen degradation. DR Reactome; R-HSA-1474228; Degradation of the extracellular matrix. DR Reactome; R-HSA-1592389; Activation of Matrix Metalloproteinases. DR Reactome; R-HSA-1679131; Trafficking and processing of endosomal TLR. DR Reactome; R-HSA-2132295; MHC class II antigen presentation. DR Reactome; R-HSA-8939242; RUNX1 regulates transcription of genes involved in differentiation of keratinocytes. DR SignaLink; P43235; -. DR SIGNOR; P43235; -. DR BioGRID-ORCS; 1513; 17 hits in 1165 CRISPR screens. DR ChiTaRS; CTSK; human. DR EvolutionaryTrace; P43235; -. DR GeneWiki; Cathepsin_K; -. DR GenomeRNAi; 1513; -. DR Pharos; P43235; Tchem. DR PRO; PR:P43235; -. DR Proteomes; UP000005640; Chromosome 1. DR RNAct; P43235; protein. DR Bgee; ENSG00000143387; Expressed in periodontal ligament and 168 other cell types or tissues. DR ExpressionAtlas; P43235; baseline and differential. DR GO; GO:0016324; C:apical plasma membrane; IEA:UniProtKB-SubCell. DR GO; GO:0036021; C:endolysosome lumen; TAS:Reactome. DR GO; GO:0009897; C:external side of plasma membrane; IEA:Ensembl. DR GO; GO:0005576; C:extracellular region; TAS:Reactome. DR GO; GO:0005615; C:extracellular space; IDA:UniProtKB. DR GO; GO:0043231; C:intracellular membrane-bounded organelle; IDA:HPA. DR GO; GO:0043202; C:lysosomal lumen; TAS:Reactome. DR GO; GO:0005764; C:lysosome; IDA:UniProtKB. DR GO; GO:0005654; C:nucleoplasm; IDA:HPA. DR GO; GO:0005518; F:collagen binding; IDA:BHF-UCL. DR GO; GO:0008656; F:cysteine-type endopeptidase activator activity involved in apoptotic process; IBA:GO_Central. DR GO; GO:0004197; F:cysteine-type endopeptidase activity; IDA:BHF-UCL. DR GO; GO:0008234; F:cysteine-type peptidase activity; IDA:MGI. DR GO; GO:0001968; F:fibronectin binding; IPI:BHF-UCL. DR GO; GO:0043394; F:proteoglycan binding; IPI:BHF-UCL. DR GO; GO:0004252; F:serine-type endopeptidase activity; TAS:Reactome. DR GO; GO:0045453; P:bone resorption; IEA:Ensembl. DR GO; GO:0071560; P:cellular response to transforming growth factor beta stimulus; IEA:Ensembl. DR GO; GO:0071356; P:cellular response to tumor necrosis factor; IEA:Ensembl. DR GO; GO:0034224; P:cellular response to zinc ion starvation; IEA:Ensembl. DR GO; GO:0030574; P:collagen catabolic process; IDA:MGI. DR GO; GO:0022617; P:extracellular matrix disassembly; TAS:Reactome. DR GO; GO:0006955; P:immune response; IBA:GO_Central. DR GO; GO:0001957; P:intramembranous ossification; IEA:Ensembl. DR GO; GO:0000423; P:mitophagy; HMP:ParkinsonsUK-UCL. DR GO; GO:1903131; P:mononuclear cell differentiation; IEA:Ensembl. DR GO; GO:0061037; P:negative regulation of cartilage development; IEA:Ensembl. DR GO; GO:2001235; P:positive regulation of apoptotic signaling pathway; IBA:GO_Central. DR GO; GO:0006508; P:proteolysis; TAS:ProtInc. DR GO; GO:0051603; P:proteolysis involved in protein catabolic process; IDA:UniProtKB. DR GO; GO:0045471; P:response to ethanol; IEA:Ensembl. DR GO; GO:0032868; P:response to insulin; IEA:Ensembl. DR GO; GO:0014070; P:response to organic cyclic compound; IEA:Ensembl. DR GO; GO:0006590; P:thyroid hormone generation; IDA:UniProtKB. DR CDD; cd02248; Peptidase_C1A; 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; IPR039417; Peptidase_C1A_papain-like. DR InterPro; IPR013201; Prot_inhib_I29. DR PANTHER; PTHR12411:SF741; CATHEPSIN K; 1. DR PANTHER; PTHR12411; CYSTEINE PROTEASE FAMILY C1-RELATED; 1. DR Pfam; PF08246; Inhibitor_I29; 1. DR Pfam; PF00112; Peptidase_C1; 1. DR PRINTS; PR00705; PAPAIN. DR SMART; SM00848; Inhibitor_I29; 1. 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; Cell membrane; Disease variant; Disulfide bond; Glycoprotein; KW Hydrolase; Lysosome; Membrane; Protease; Proteomics identification; KW Reference proteome; Secreted; Signal; Thiol protease; Zymogen. FT SIGNAL 1..15 FT /evidence="ECO:0000255" FT PROPEP 16..114 FT /note="Activation peptide" FT /id="PRO_0000026295" FT CHAIN 115..329 FT /note="Cathepsin K" FT /id="PRO_0000026296" FT ACT_SITE 139 FT /evidence="ECO:0000250" FT ACT_SITE 276 FT /evidence="ECO:0000250" FT ACT_SITE 296 FT /evidence="ECO:0000250" FT CARBOHYD 103 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000255" FT DISULFID 136..177 FT DISULFID 170..210 FT DISULFID 269..318 FT VARIANT 79 FT /note="G -> E (in PKND; dbSNP:rs74315305)" FT /evidence="ECO:0000269|PubMed:10491211, FT ECO:0000269|PubMed:10878663" FT /id="VAR_015738" FT VARIANT 122 FT /note="R -> P (in PKND)" FT /evidence="ECO:0000269|PubMed:22822386" FT /id="VAR_074023" FT VARIANT 146 FT /note="G -> R (in PKND; dbSNP:rs74315302)" FT /evidence="ECO:0000269|PubMed:8703060" FT /id="VAR_006725" FT VARIANT 277 FT /note="A -> V (in PKND; dbSNP:rs74315304)" FT /evidence="ECO:0000269|PubMed:22822386, FT ECO:0000269|PubMed:9529353" FT /id="VAR_015739" FT VARIANT 283 FT /note="Y -> C (in PKND; does not affect protein level; does FT not detect cysteine-type endopeptidase activity)" FT /evidence="ECO:0000269|PubMed:25731711" FT /id="VAR_074024" FT VARIANT 309 FT /note="L -> P (in PKND; dbSNP:rs29001685)" FT /evidence="ECO:0000269|PubMed:10878663" FT /id="VAR_006726" FT CONFLICT 46 FT /note="R -> P (in Ref. 3; AAA95998)" FT /evidence="ECO:0000305" FT HELIX 20..22 FT /evidence="ECO:0007829|PDB:5Z5O" FT HELIX 24..33 FT /evidence="ECO:0007829|PDB:7QBM" FT HELIX 40..65 FT /evidence="ECO:0007829|PDB:7QBM" FT STRAND 70..73 FT /evidence="ECO:0007829|PDB:7QBM" FT TURN 77..80 FT /evidence="ECO:0007829|PDB:7QBM" FT HELIX 83..86 FT /evidence="ECO:0007829|PDB:7QBM" FT HELIX 103..105 FT /evidence="ECO:0007829|PDB:5Z5O" FT HELIX 121..124 FT /evidence="ECO:0007829|PDB:4X6H" FT STRAND 135..137 FT /evidence="ECO:0007829|PDB:3KX1" FT HELIX 139..156 FT /evidence="ECO:0007829|PDB:4X6H" FT HELIX 164..170 FT /evidence="ECO:0007829|PDB:4X6H" FT STRAND 172..174 FT /evidence="ECO:0007829|PDB:6QL8" FT HELIX 176..178 FT /evidence="ECO:0007829|PDB:4X6H" FT HELIX 182..192 FT /evidence="ECO:0007829|PDB:4X6H" FT STRAND 195..197 FT /evidence="ECO:0007829|PDB:4X6H" FT TURN 198..200 FT /evidence="ECO:0007829|PDB:4X6H" FT HELIX 214..216 FT /evidence="ECO:0007829|PDB:4X6H" FT STRAND 217..219 FT /evidence="ECO:0007829|PDB:4X6H" FT STRAND 223..226 FT /evidence="ECO:0007829|PDB:4X6H" FT HELIX 232..242 FT /evidence="ECO:0007829|PDB:4X6H" FT STRAND 245..249 FT /evidence="ECO:0007829|PDB:4X6H" FT HELIX 254..257 FT /evidence="ECO:0007829|PDB:4X6H" FT STRAND 261..264 FT /evidence="ECO:0007829|PDB:4X6H" FT STRAND 276..286 FT /evidence="ECO:0007829|PDB:4X6H" FT STRAND 289..295 FT /evidence="ECO:0007829|PDB:4X6H" FT STRAND 300..302 FT /evidence="ECO:0007829|PDB:3H7D" FT TURN 303..305 FT /evidence="ECO:0007829|PDB:1AYV" FT STRAND 307..316 FT /evidence="ECO:0007829|PDB:4X6H" FT HELIX 317..319 FT /evidence="ECO:0007829|PDB:4X6H" FT TURN 320..322 FT /evidence="ECO:0007829|PDB:3KX1" FT STRAND 325..328 FT /evidence="ECO:0007829|PDB:4X6H" SQ SEQUENCE 329 AA; 36966 MW; 4677C3C89FF4CE85 CRC64; MWGLKVLLLP VVSFALYPEE ILDTHWELWK KTHRKQYNNK VDEISRRLIW EKNLKYISIH NLEASLGVHT YELAMNHLGD MTSEEVVQKM TGLKVPLSHS RSNDTLYIPE WEGRAPDSVD YRKKGYVTPV KNQGQCGSCW AFSSVGALEG QLKKKTGKLL NLSPQNLVDC VSENDGCGGG YMTNAFQYVQ KNRGIDSEDA YPYVGQEESC MYNPTGKAAK CRGYREIPEG NEKALKRAVA RVGPVSVAID ASLTSFQFYS KGVYYDESCN SDNLNHAVLA VGYGIQKGNK HWIIKNSWGE NWGNKGYILM ARNKNNACGI ANLASFPKM //