CATK_MOUSE
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 03-AUG-2022, entry version 171.
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/jci200315990;
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 GlyGen; P55097; 2 sites.
DR iPTMnet; P55097; -.
DR PhosphoSitePlus; P55097; -.
DR PaxDb; P55097; -.
DR PeptideAtlas; P55097; -.
DR PRIDE; P55097; -.
DR ProteomicsDB; 279921; -.
DR Antibodypedia; 34039; 616 antibodies from 37 providers.
DR DNASU; 13038; -.
DR Ensembl; ENSMUST00000015664; ENSMUSP00000015664; ENSMUSG00000028111.
DR GeneID; 13038; -.
DR KEGG; mmu:13038; -.
DR UCSC; uc008qjy.2; mouse.
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; PVGNEKA; -.
DR OrthoDB; 1275401at2759; -.
DR PhylomeDB; P55097; -.
DR TreeFam; TF313739; -.
DR BioCyc; MetaCyc:MON-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 74 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 189 other tissues.
DR ExpressionAtlas; P55097; baseline and differential.
DR Genevisible; P55097; MM.
DR GO; GO:0016324; C:apical plasma membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0005737; C:cytoplasm; ISO:MGI.
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: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: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:0061037; P:negative regulation of cartilage development; IMP:MGI.
DR GO; GO:0051603; P:proteolysis involved in protein catabolic process; IMP:UniProtKB.
DR GO; GO:0006590; P:thyroid hormone generation; IMP:UniProtKB.
DR CDD; cd02248; Peptidase_C1A; 1.
DR InterPro; IPR038765; Papain-like_cys_pep_sf.
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; 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_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
