CATK_HUMAN
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 03-AUG-2022, entry version 208.
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}.
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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 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 AlphaFoldDB; P43235; -.
DR SMR; P43235; -.
DR BioGRID; 107893; 14.
DR DIP; DIP-39993N; -.
DR IntAct; P43235; 9.
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; 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 GlyGen; P43235; 1 site.
DR iPTMnet; P43235; -.
DR PhosphoSitePlus; P43235; -.
DR BioMuta; CTSK; -.
DR DMDM; 1168793; -.
DR EPD; P43235; -.
DR jPOST; P43235; -.
DR MassIVE; P43235; -.
DR PaxDb; P43235; -.
DR PeptideAtlas; P43235; -.
DR PRIDE; P43235; -.
DR ProteomicsDB; 55598; -.
DR Antibodypedia; 34039; 616 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 CTD; 1513; -.
DR DisGeNET; 1513; -.
DR GeneCards; CTSK; -.
DR GeneReviews; CTSK; -.
DR HGNC; HGNC:2536; CTSK.
DR HPA; ENSG00000143387; Tissue enhanced (cervix, endometrium).
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; PVGNEKA; -.
DR OrthoDB; 1275401at2759; -.
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; 15 hits in 1081 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 166 other tissues.
DR ExpressionAtlas; P43235; baseline and differential.
DR Genevisible; P43235; HS.
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: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:0000422; P:autophagy of mitochondrion; HMP:ParkinsonsUK-UCL.
DR GO; GO:0045453; P:bone resorption; IEA:Ensembl.
DR GO; GO:0030574; P:collagen catabolic process; IDA:BHF-UCL.
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:0061037; P:negative regulation of cartilage development; IEA:Ensembl.
DR GO; GO:0006508; P:proteolysis; TAS:ProtInc.
DR GO; GO:0051603; P:proteolysis involved in protein catabolic process; IDA:UniProtKB.
DR GO; GO:0006590; P:thyroid hormone generation; IDA:UniProtKB.
DR CDD; cd02248; Peptidase_C1A; 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; IPR000668; Peptidase_C1A_C.
DR InterPro; IPR015644; Peptidase_C1A_cathepsin-K.
DR InterPro; IPR039417; Peptidase_C1A_papain-like.
DR InterPro; IPR013201; Prot_inhib_I29.
DR PANTHER; PTHR12411:SF55; PTHR12411:SF55; 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; 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; Cell membrane; Disease variant; Disulfide bond; Glycoprotein;
KW Hydrolase; Lysosome; Membrane; Protease; Reference proteome; Secreted;
KW 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
