CATK_RAT
ID CATK_RAT Reviewed; 329 AA.
AC O35186;
DT 24-JAN-2001, integrated into UniProtKB/Swiss-Prot.
DT 01-JAN-1998, sequence version 1.
DT 03-AUG-2022, entry version 151.
DE RecName: Full=Cathepsin K;
DE EC=3.4.22.38;
DE Flags: Precursor;
GN Name=Ctsk;
OS Rattus norvegicus (Rat).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Rattus.
OX NCBI_TaxID=10116;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC STRAIN=Wistar; TISSUE=Bone;
RA Payne J.A., Miller L.R.;
RL Submitted (JUN-1997) to the EMBL/GenBank/DDBJ databases.
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Testis;
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).
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 -!- 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; AF010306; AAB65743.1; -; mRNA.
DR EMBL; BC078793; AAH78793.1; -; mRNA.
DR RefSeq; NP_113748.1; NM_031560.2.
DR AlphaFoldDB; O35186; -.
DR SMR; O35186; -.
DR STRING; 10116.ENSRNOP00000028730; -.
DR BindingDB; O35186; -.
DR ChEMBL; CHEMBL3034; -.
DR MEROPS; C01.036; -.
DR MEROPS; I29.007; -.
DR GlyGen; O35186; 2 sites.
DR iPTMnet; O35186; -.
DR PhosphoSitePlus; O35186; -.
DR PaxDb; O35186; -.
DR PRIDE; O35186; -.
DR Ensembl; ENSRNOT00000028730; ENSRNOP00000028730; ENSRNOG00000021155.
DR GeneID; 29175; -.
DR KEGG; rno:29175; -.
DR UCSC; RGD:61810; rat.
DR CTD; 1513; -.
DR RGD; 61810; Ctsk.
DR eggNOG; KOG1543; Eukaryota.
DR GeneTree; ENSGT00940000157759; -.
DR HOGENOM; CLU_012184_1_2_1; -.
DR InParanoid; O35186; -.
DR OMA; PVGNEKA; -.
DR OrthoDB; 1275401at2759; -.
DR PhylomeDB; O35186; -.
DR TreeFam; TF313739; -.
DR BRENDA; 3.4.22.38; 5301.
DR Reactome; R-RNO-1442490; Collagen degradation.
DR Reactome; R-RNO-1474228; Degradation of the extracellular matrix.
DR Reactome; R-RNO-1592389; Activation of Matrix Metalloproteinases.
DR Reactome; R-RNO-1679131; Trafficking and processing of endosomal TLR.
DR Reactome; R-RNO-2132295; MHC class II antigen presentation.
DR Reactome; R-RNO-8939242; RUNX1 regulates transcription of genes involved in differentiation of keratinocytes.
DR PRO; PR:O35186; -.
DR Proteomes; UP000002494; Chromosome 2.
DR Bgee; ENSRNOG00000021155; Expressed in ovary and 20 other tissues.
DR Genevisible; O35186; RN.
DR GO; GO:0016324; C:apical plasma membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0005737; C:cytoplasm; IDA:RGD.
DR GO; GO:0009897; C:external side of plasma membrane; ISO:RGD.
DR GO; GO:0005615; C:extracellular space; IDA:RGD.
DR GO; GO:0005764; C:lysosome; IDA:RGD.
DR GO; GO:0005654; C:nucleoplasm; IEA:Ensembl.
DR GO; GO:0005518; F:collagen binding; ISO:RGD.
DR GO; GO:0004197; F:cysteine-type endopeptidase activity; ISO:RGD.
DR GO; GO:0008234; F:cysteine-type peptidase activity; ISO:RGD.
DR GO; GO:0001968; F:fibronectin binding; ISO:RGD.
DR GO; GO:0043394; F:proteoglycan binding; ISO:RGD.
DR GO; GO:0045453; P:bone resorption; IMP:RGD.
DR GO; GO:0030574; P:collagen catabolic process; ISO:RGD.
DR GO; GO:0006955; P:immune response; IBA:GO_Central.
DR GO; GO:0001957; P:intramembranous ossification; IEP:RGD.
DR GO; GO:0061037; P:negative regulation of cartilage development; ISO:RGD.
DR GO; GO:0006508; P:proteolysis; TAS:RGD.
DR GO; GO:0051603; P:proteolysis involved in protein catabolic process; ISO:RGD.
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 2: Evidence at transcript level;
KW Cell membrane; Disulfide bond; Glycoprotein; Hydrolase; Lysosome; Membrane;
KW Protease; Reference proteome; Secreted; Signal; Thiol protease; Zymogen.
FT SIGNAL 1..15
FT /evidence="ECO:0000255"
FT PROPEP 16..114
FT /note="Activation peptide"
FT /id="PRO_0000026307"
FT CHAIN 115..329
FT /note="Cathepsin K"
FT /id="PRO_0000026308"
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"
SQ SEQUENCE 329 AA; 36791 MW; B416008509CF606A CRC64;
MWVFKFLLLP VVSFALSPEE TLDTQWELWK KTHGKQYNSK VDEISRRLIW EKNLKKISVH
NLEASLGAHT YELAMNHLGD MTSEEVVQKM TGLRVPPSRS FSNDTLYTPE WEGRVPDSID
YRKKGYVTPV KNQGQCGSCW AFSSAGALEG QLKKKTGKLL ALSPQNLVDC VSENYGCGGG
YMTTAFQYVQ QNGGIDSEDA YPYVGQDESC MYNATAKAAK CRGYREIPVG NEKALKRAVA
RVGPVSVSID ASLTSFQFYS RGVYYDENCD RDNVNHAVLV VGYGTQKGNK YWIIKNSWGE
SWGNKGYVLL ARNKNNACGI TNLASFPKM
