ID   CATK_MOUSE              Reviewed;         329 AA.
AC   P55097; O88718;
DT   01-OCT-1996, integrated into UniProtKB/Swiss-Prot.
DT   01-DEC-2000, sequence version 2.
DT   27-MAR-2024, entry version 180.
DE   RecName: Full=Cathepsin K;
DE            EC=3.4.22.38;
DE   Flags: Precursor;
GN   Name=Ctsk;
OS   Mus musculus (Mouse).
OC   Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC   Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC   Murinae; Mus; Mus.
OX   NCBI_TaxID=10090;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [MRNA], TISSUE SPECIFICITY, AND DEVELOPMENTAL STAGE.
RC   STRAIN=C57BL/6J; TISSUE=Calvaria;
RX   PubMed=8814310; DOI=10.1016/0014-5793(96)00907-6;
RA   Rantakokko J.A., Aro H.T., Savontaus M., Vuorio E.;
RT   "Mouse cathepsin K: cDNA cloning and predominant expression of the gene in
RT   osteoclasts, and in some hypertrophying chondrocytes during mouse
RT   development.";
RL   FEBS Lett. 393:307-313(1996).
RN   [2]
RP   NUCLEOTIDE SEQUENCE.
RC   STRAIN=129/SvJ;
RX   PubMed=10372556; DOI=10.1016/s0945-053x(99)00010-4;
RA   Rantakokko J.A., Kiviranta R., Eerola R., Aro H.T., Vuorio E.;
RT   "Complete genomic structure of the mouse cathepsin K gene (Ctsk) and its
RT   localization next to the Arnt gene on mouse chromosome 3.";
RL   Matrix Biol. 18:155-161(1999).
RN   [3]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC   TISSUE=Olfactory epithelium;
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   [4]
RP   FUNCTION, SUBCELLULAR LOCATION, TISSUE SPECIFICITY, AND DISRUPTION
RP   PHENOTYPE.
RX   PubMed=12782676; DOI=10.1172/jci15990;
RA   Friedrichs B., Tepel C., Reinheckel T., Deussing J., von Figura K.,
RA   Herzog V., Peters C., Saftig P., Brix K.;
RT   "Thyroid functions of mouse cathepsins B, K, and L.";
RL   J. Clin. Invest. 111:1733-1745(2003).
CC   -!- FUNCTION: Thiol protease involved in osteoclastic bone resorption.
CC       Displays potent endoprotease activity against fibrinogen at acid pH.
CC       May play an important role in extracellular matrix degradation (By
CC       similarity). Involved in the release of thyroid hormone thyroxine (T4)
CC       by limited proteolysis of TG/thyroglobulin in the thyroid follicle
CC       lumen (PubMed:12782676). {ECO:0000250, ECO:0000269|PubMed:12782676}.
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:12782676}. Secreted
CC       {ECO:0000269|PubMed:12782676}. Apical cell membrane
CC       {ECO:0000269|PubMed:12782676}; Peripheral membrane protein
CC       {ECO:0000269|PubMed:12782676}; Extracellular side
CC       {ECO:0000269|PubMed:12782676}. Note=Localizes to the lumen of thyroid
CC       follicles and to the apical membrane of thyroid epithelial cells.
CC       {ECO:0000269|PubMed:12782676}.
CC   -!- TISSUE SPECIFICITY: Predominantly expressed in bones (PubMed:8814310).
CC       Expressed in thyroid epithelial cells (PubMed:12782676).
CC       {ECO:0000269|PubMed:12782676, ECO:0000269|PubMed:8814310}.
CC   -!- DEVELOPMENTAL STAGE: Expressed in new born and adults.
CC       {ECO:0000269|PubMed:8814310}.
CC   -!- DISRUPTION PHENOTYPE: Enlarged thyroid follicles, reduced extension of
CC       the thyroid epithelium, and slight increase in the levels of
CC       Tg/thyroglobulin in the thyroid follicles. Loss of localization of
CC       CTSB/cathepsin B and L to the apical membrane of thyroid epithelial
CC       cells. Serum levels of thyroid hormone thyroxine (T4) are normal.
CC       However, reduction in T4 levels is more severe in CTSK and CTSL double
CC       knockout mice compared to CTSL double knockout mice.
CC       {ECO:0000269|PubMed:12782676}.
CC   -!- SIMILARITY: Belongs to the peptidase C1 family. {ECO:0000255|PROSITE-
CC       ProRule:PRU10088, ECO:0000255|PROSITE-ProRule:PRU10089}.
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DR   EMBL; X94444; CAA64218.1; -; mRNA.
DR   EMBL; AJ006033; CAA06825.1; -; Genomic_DNA.
DR   EMBL; BC046320; AAH46320.1; -; mRNA.
DR   CCDS; CCDS17615.1; -.
DR   PIR; S74227; S74227.
DR   RefSeq; NP_031828.2; NM_007802.4.
DR   RefSeq; XP_006501037.1; XM_006500974.3.
DR   PDB; 5T6U; X-ray; 2.90 A; A=115-329.
DR   PDB; 6BKI; X-ray; 2.94 A; A/B=115-329.
DR   PDBsum; 5T6U; -.
DR   PDBsum; 6BKI; -.
DR   AlphaFoldDB; P55097; -.
DR   SMR; P55097; -.
DR   IntAct; P55097; 1.
DR   MINT; P55097; -.
DR   STRING; 10090.ENSMUSP00000015664; -.
DR   ChEMBL; CHEMBL1075277; -.
DR   MEROPS; C01.036; -.
DR   MEROPS; I29.007; -.
DR   GlyCosmos; P55097; 2 sites, No reported glycans.
DR   GlyGen; P55097; 2 sites.
DR   iPTMnet; P55097; -.
DR   PhosphoSitePlus; P55097; -.
DR   PaxDb; 10090-ENSMUSP00000015664; -.
DR   PeptideAtlas; P55097; -.
DR   ProteomicsDB; 279921; -.
DR   Antibodypedia; 34039; 653 antibodies from 37 providers.
DR   DNASU; 13038; -.
DR   Ensembl; ENSMUST00000015664.5; ENSMUSP00000015664.4; ENSMUSG00000028111.5.
DR   GeneID; 13038; -.
DR   KEGG; mmu:13038; -.
DR   UCSC; uc008qjy.2; mouse.
DR   AGR; MGI:107823; -.
DR   CTD; 1513; -.
DR   MGI; MGI:107823; Ctsk.
DR   VEuPathDB; HostDB:ENSMUSG00000028111; -.
DR   eggNOG; KOG1543; Eukaryota.
DR   GeneTree; ENSGT00940000157759; -.
DR   HOGENOM; CLU_012184_1_2_1; -.
DR   InParanoid; P55097; -.
DR   OMA; ETWGNKG; -.
DR   OrthoDB; 5472948at2759; -.
DR   PhylomeDB; P55097; -.
DR   TreeFam; TF313739; -.
DR   BioCyc; MetaCyc:MONOMER-14811; -.
DR   BRENDA; 3.4.22.38; 3474.
DR   Reactome; R-MMU-1442490; Collagen degradation.
DR   Reactome; R-MMU-1474228; Degradation of the extracellular matrix.
DR   Reactome; R-MMU-1592389; Activation of Matrix Metalloproteinases.
DR   Reactome; R-MMU-1679131; Trafficking and processing of endosomal TLR.
DR   Reactome; R-MMU-2132295; MHC class II antigen presentation.
DR   Reactome; R-MMU-8939242; RUNX1 regulates transcription of genes involved in differentiation of keratinocytes.
DR   BioGRID-ORCS; 13038; 1 hit in 79 CRISPR screens.
DR   ChiTaRS; Ctsk; mouse.
DR   PRO; PR:P55097; -.
DR   Proteomes; UP000000589; Chromosome 3.
DR   RNAct; P55097; Protein.
DR   Bgee; ENSMUSG00000028111; Expressed in hindlimb long bone and 192 other cell types or tissues.
DR   ExpressionAtlas; P55097; baseline and differential.
DR   GO; GO:0016324; C:apical plasma membrane; IEA:UniProtKB-SubCell.
DR   GO; GO:0009897; C:external side of plasma membrane; IDA:UniProtKB.
DR   GO; GO:0005615; C:extracellular space; IDA:UniProtKB.
DR   GO; GO:0043231; C:intracellular membrane-bounded organelle; ISO:MGI.
DR   GO; GO:0005764; C:lysosome; IDA:UniProtKB.
DR   GO; GO:0005654; C:nucleoplasm; ISO:MGI.
DR   GO; GO:0005518; F:collagen binding; ISO:MGI.
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; ISO:MGI.
DR   GO; GO:0008234; F:cysteine-type peptidase activity; ISO:MGI.
DR   GO; GO:0001968; F:fibronectin binding; ISO:MGI.
DR   GO; GO:0043394; F:proteoglycan binding; ISO:MGI.
DR   GO; GO:0045453; P:bone resorption; IMP:MGI.
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; IMP:MGI.
DR   GO; GO:0006955; P:immune response; IBA:GO_Central.
DR   GO; GO:0001957; P:intramembranous ossification; IEA:Ensembl.
DR   GO; GO:1903131; P:mononuclear cell differentiation; IEA:Ensembl.
DR   GO; GO:0061037; P:negative regulation of cartilage development; IMP:MGI.
DR   GO; GO:2001235; P:positive regulation of apoptotic signaling pathway; IBA:GO_Central.
DR   GO; GO:0006508; P:proteolysis; ISO:MGI.
DR   GO; GO:0051603; P:proteolysis involved in protein catabolic process; IMP: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; IMP: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; 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; PS00139; THIOL_PROTEASE_CYS; 1.
DR   PROSITE; PS00639; THIOL_PROTEASE_HIS; 1.
DR   Genevisible; P55097; MM.
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_0000026301"
FT   CHAIN           115..329
FT                   /note="Cathepsin K"
FT                   /id="PRO_0000026302"
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        213
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000255"
FT   DISULFID        136..177
FT                   /evidence="ECO:0000250"
FT   DISULFID        170..210
FT                   /evidence="ECO:0000250"
FT   DISULFID        269..318
FT                   /evidence="ECO:0000250"
FT   CONFLICT        3..6
FT                   /note="VFKF -> GLKV (in Ref. 1; CAA64218)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        201
FT                   /note="Y -> F (in Ref. 1; CAA64218)"
FT                   /evidence="ECO:0000305"
FT   TURN            121..125
FT                   /evidence="ECO:0007829|PDB:5T6U"
FT   HELIX           139..156
FT                   /evidence="ECO:0007829|PDB:5T6U"
FT   HELIX           164..170
FT                   /evidence="ECO:0007829|PDB:5T6U"
FT   HELIX           176..178
FT                   /evidence="ECO:0007829|PDB:5T6U"
FT   HELIX           182..192
FT                   /evidence="ECO:0007829|PDB:5T6U"
FT   STRAND          195..197
FT                   /evidence="ECO:0007829|PDB:5T6U"
FT   TURN            198..200
FT                   /evidence="ECO:0007829|PDB:5T6U"
FT   HELIX           214..216
FT                   /evidence="ECO:0007829|PDB:5T6U"
FT   STRAND          217..219
FT                   /evidence="ECO:0007829|PDB:5T6U"
FT   STRAND          224..226
FT                   /evidence="ECO:0007829|PDB:5T6U"
FT   HELIX           232..241
FT                   /evidence="ECO:0007829|PDB:5T6U"
FT   STRAND          244..249
FT                   /evidence="ECO:0007829|PDB:5T6U"
FT   HELIX           254..257
FT                   /evidence="ECO:0007829|PDB:5T6U"
FT   STRAND          261..264
FT                   /evidence="ECO:0007829|PDB:5T6U"
FT   STRAND          271..273
FT                   /evidence="ECO:0007829|PDB:5T6U"
FT   STRAND          276..286
FT                   /evidence="ECO:0007829|PDB:5T6U"
FT   STRAND          289..295
FT                   /evidence="ECO:0007829|PDB:5T6U"
FT   STRAND          307..311
FT                   /evidence="ECO:0007829|PDB:5T6U"
FT   STRAND          313..316
FT                   /evidence="ECO:0007829|PDB:5T6U"
FT   HELIX           317..319
FT                   /evidence="ECO:0007829|PDB:5T6U"
FT   TURN            320..323
FT                   /evidence="ECO:0007829|PDB:5T6U"
FT   STRAND          325..327
FT                   /evidence="ECO:0007829|PDB:5T6U"
SQ   SEQUENCE   329 AA;  36889 MW;  4F4B28F664925778 CRC64;
     MWVFKFLLLP MVSFALSPEE MLDTQWELWK KTHQKQYNSK VDEISRRLIW EKNLKQISAH
     NLEASLGVHT YELAMNHLGD MTSEEVVQKM TGLRIPPSRS YSNDTLYTPE WEGRVPDSID
     YRKKGYVTPV KNQGQCGSCW AFSSAGALEG QLKKKTGKLL ALSPQNLVDC VTENYGCGGG
     YMTTAFQYVQ QNGGIDSEDA YPYVGQDESC MYNATAKAAK CRGYREIPVG NEKALKRAVA
     RVGPISVSID ASLASFQFYS RGVYYDENCD RDNVNHAVLV VGYGTQKGSK HWIIKNSWGE
     SWGNKGYALL ARNKNNACGI TNMASFPKM
//