ID CATK_RABIT Reviewed; 329 AA. AC P43236; DT 01-NOV-1995, integrated into UniProtKB/Swiss-Prot. DT 01-NOV-1995, sequence version 1. DT 02-SEP-2026, entry version 153. DE RecName: Full=Cathepsin K; DE EC=3.4.22.38; DE AltName: Full=Protein OC-2; DE Flags: Precursor; GN Name=CTSK; OS Oryctolagus cuniculus (Rabbit). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; OC Eutheria; Euarchontoglires; Glires; Lagomorpha; Leporidae; Oryctolagus. OX NCBI_TaxID=9986; RN [1] RP NUCLEOTIDE SEQUENCE [MRNA], AND TISSUE SPECIFICITY. RC TISSUE=Bone; RX PubMed=8288568; DOI=10.1016/s0021-9258(17)42227-7; RA Tezuka K., Tezuka Y., Maejima A., Sato T., Nemoto K., Kamioka H., RA Hakeda Y., Kumegawa M.; RT "Molecular cloning of a possible cysteine proteinase predominantly RT expressed in osteoclasts."; RL J. Biol. Chem. 269:1106-1109(1994). RN [2] RP X-RAY CRYSTALLOGRAPHY (1.9 ANGSTROMS) OF 115-329 IN COMPLEX WITH RP INHIBITORS, AND DISULFIDE BONDS. RX PubMed=16451072; DOI=10.1021/jm051059p; RA Crane S.N., Black W.C., Palmer J.T., Davis D.E., Setti E., Robichaud J., RA Paquet J., Oballa R.M., Bayly C.I., McKay D.J., Somoza J.R., Chauret N., RA Seto C., Scheigetz J., Wesolowski G., Masse F., Desmarais S., Ouellet M.; RT "Beta-substituted cyclohexanecarboxamide: a nonpeptidic framework for the RT design of potent inhibitors of cathepsin K."; RL J. Med. Chem. 49:1066-1079(2006). 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. CC {ECO:0000250|UniProtKB:P43235}. 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:0000250|UniProtKB:P43235}. Secreted CC {ECO:0000250|UniProtKB:P43235}. Apical cell membrane CC {ECO:0000250|UniProtKB:P43235}; Peripheral membrane protein CC {ECO:0000250|UniProtKB:P43235}; Extracellular side CC {ECO:0000250|UniProtKB:P43235}. Note=Localizes to the lumen of thyroid CC follicles and to the apical membrane of thyroid epithelial cells. CC {ECO:0000250|UniProtKB:P43235}. CC -!- TISSUE SPECIFICITY: Predominantly expressed in osteclasts (bones). CC {ECO:0000269|PubMed:8288568}. 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; D14036; BAA03125.1; -; mRNA. DR PIR; A49868; A49868. DR RefSeq; NP_001076110.1; NM_001082641.1. DR RefSeq; XP_017200979.1; XM_017345490.3. DR PDB; 2F7D; X-ray; 1.90 A; A=115-329. DR AlphaFoldDB; P43236; -. DR SMR; P43236; -. DR FunCoup; P43236; 37. DR STRING; 9986.ENSOCUP00000009540; -. DR BindingDB; P43236; -. DR ChEMBL; CHEMBL3349; -. DR MEROPS; C01.036; -. DR MEROPS; I29.007; -. DR GlyCosmos; P43236; 2 sites, No reported glycans. DR PaxDb; 9986-ENSOCUP00000009540; -. DR Ensembl; ENSOCUT00000011087.2; ENSOCUP00000009540.2; ENSOCUG00000011090.2. DR GeneID; 100009334; -. DR KEGG; ocu:100009334; -. DR CTD; 1513; -. DR eggNOG; KOG1543; Eukaryota. DR GeneTree; ENSGT00940000157759; -. DR HOGENOM; CLU_012184_1_2_1; -. DR InParanoid; P43236; -. DR OMA; EGETCCC; -. DR OrthoDB; 65740at2759; -. DR EvolutionaryTrace; P43236; -. DR PRO; PR:P43236; -. DR Proteomes; UP000001811; Chromosome 13. DR Bgee; ENSOCUG00000011090; Expressed in aorta and 18 other cell types or tissues. DR GO; GO:0016324; C:apical plasma membrane; ISS:UniProtKB. DR GO; GO:0009897; C:external side of plasma membrane; IEA:Ensembl. DR GO; GO:0005576; C:extracellular region; ISS:UniProtKB. DR GO; GO:0005764; C:lysosome; ISS:UniProtKB. DR GO; GO:0005518; F:collagen binding; IEA:Ensembl. DR GO; GO:0004197; F:cysteine-type endopeptidase activity; IEA:UniProtKB-EC. DR GO; GO:0001968; F:fibronectin binding; IEA:Ensembl. DR GO; GO:0043394; F:proteoglycan binding; IEA:Ensembl. DR GO; GO:0030574; P:collagen catabolic process; IEA:Ensembl. DR GO; GO:0030163; P:protein catabolic process; IEA:Ensembl. DR GO; GO:0006508; P:proteolysis; IEA:InterPro. DR GO; GO:0006590; P:thyroid hormone generation; ISS:UniProtKB. DR CDD; cd02248; Peptidase_C1A; 1. DR FunFam; 3.90.70.10:FF:000006; Cathepsin S; 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; 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. DR PDBsum; 2F7D; -. PE 1: Evidence at protein level; KW 3D-structure; Cell membrane; Disulfide bond; Glycoprotein; Hydrolase; KW Lysosome; Membrane; Protease; Reference proteome; Secreted; Signal; KW Thiol protease; Zymogen. FT SIGNAL 1..15 FT /evidence="ECO:0000255" FT PROPEP 16..114 FT /note="Activation peptide" FT /id="PRO_0000026305" FT CHAIN 115..329 FT /note="Cathepsin K" FT /id="PRO_0000026306" 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 CARBOHYD 268 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000255" FT DISULFID 136..177 FT /evidence="ECO:0000269|PubMed:16451072" FT DISULFID 170..210 FT /evidence="ECO:0000269|PubMed:16451072" FT DISULFID 269..318 FT /evidence="ECO:0000269|PubMed:16451072" FT HELIX 121..124 FT /evidence="ECO:0007829|PDB:2F7D" FT HELIX 128..130 FT /evidence="ECO:0007829|PDB:2F7D" FT HELIX 139..156 FT /evidence="ECO:0007829|PDB:2F7D" FT HELIX 164..170 FT /evidence="ECO:0007829|PDB:2F7D" FT HELIX 176..178 FT /evidence="ECO:0007829|PDB:2F7D" FT HELIX 182..192 FT /evidence="ECO:0007829|PDB:2F7D" FT STRAND 195..197 FT /evidence="ECO:0007829|PDB:2F7D" FT HELIX 198..200 FT /evidence="ECO:0007829|PDB:2F7D" FT HELIX 214..216 FT /evidence="ECO:0007829|PDB:2F7D" FT STRAND 217..219 FT /evidence="ECO:0007829|PDB:2F7D" FT STRAND 224..226 FT /evidence="ECO:0007829|PDB:2F7D" FT HELIX 232..241 FT /evidence="ECO:0007829|PDB:2F7D" FT STRAND 245..249 FT /evidence="ECO:0007829|PDB:2F7D" FT HELIX 254..257 FT /evidence="ECO:0007829|PDB:2F7D" FT STRAND 261..264 FT /evidence="ECO:0007829|PDB:2F7D" FT STRAND 276..286 FT /evidence="ECO:0007829|PDB:2F7D" FT STRAND 289..295 FT /evidence="ECO:0007829|PDB:2F7D" FT STRAND 307..316 FT /evidence="ECO:0007829|PDB:2F7D" FT HELIX 317..319 FT /evidence="ECO:0007829|PDB:2F7D" FT STRAND 325..327 FT /evidence="ECO:0007829|PDB:2F7D" SQ SEQUENCE 329 AA; 36870 MW; 875D8582876EB51F CRC64; MWGLKVLLLP VVSFALHPEE ILDTQWELWK KTYSKQYNSK VDEISRRLIW EKNLKHISIH NLEASLGVHT YELAMNHLGD MTSEEVVQKM TGLKVPPSRS HSNDTLYIPD WEGRTPDSID YRKKGYVTPV KNQGQCGSCW AFSSVGALEG QLKKKTGKLL NLSPQNLVDC VSENYGCGGG YMTNAFQYVQ RNRGIDSEDA YPYVGQDESC MYNPTGKAAK CRGYREIPEG NEKALKRAVA RVGPVSVAID ASLTSFQFYS KGVYYDENCS SDNVNHAVLA VGYGIQKGNK HWIIKNSWGE SWGNKGYILM ARNKNNACGI ANLASFPKM //