CATK_RABIT
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 03-AUG-2022, entry version 139.
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}.
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DR EMBL; D14036; BAA03125.1; -; mRNA.
DR PIR; A49868; A49868.
DR RefSeq; NP_001076110.1; NM_001082641.1.
DR RefSeq; XP_017200979.1; XM_017345490.1.
DR PDB; 2F7D; X-ray; 1.90 A; A=115-329.
DR PDBsum; 2F7D; -.
DR AlphaFoldDB; P43236; -.
DR SMR; P43236; -.
DR STRING; 9986.ENSOCUP00000009540; -.
DR BindingDB; P43236; -.
DR ChEMBL; CHEMBL3349; -.
DR MEROPS; C01.036; -.
DR MEROPS; I29.007; -.
DR Ensembl; ENSOCUT00000011087; ENSOCUP00000009540; ENSOCUG00000011090.
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; PVGNEKA; -.
DR OrthoDB; 1275401at2759; -.
DR TreeFam; TF313739; -.
DR EvolutionaryTrace; P43236; -.
DR PRO; PR:P43236; -.
DR Proteomes; UP000001811; Chromosome 13.
DR Bgee; ENSOCUG00000011090; Expressed in aorta and 18 other tissues.
DR GO; GO:0016324; C:apical plasma membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0009897; C:external side of plasma membrane; IEA:Ensembl.
DR GO; GO:0005615; C:extracellular space; ISS:UniProtKB.
DR GO; GO:0005764; C:lysosome; ISS:UniProtKB.
DR GO; GO:0005654; C:nucleoplasm; IEA:Ensembl.
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:0045453; P:bone resorption; IEA:Ensembl.
DR GO; GO:0030574; P:collagen catabolic process; IEA:Ensembl.
DR GO; GO:0061037; P:negative regulation of cartilage development; IEA:Ensembl.
DR GO; GO:0051603; P:proteolysis involved in protein catabolic process; IEA:Ensembl.
DR GO; GO:0006590; P:thyroid hormone generation; ISS: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; 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 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
