CATK_MACMU
ID CATK_MACMU Reviewed; 329 AA.
AC P61277; O77641;
DT 10-MAY-2004, integrated into UniProtKB/Swiss-Prot.
DT 10-MAY-2004, sequence version 1.
DT 03-AUG-2022, entry version 118.
DE RecName: Full=Cathepsin K;
DE EC=3.4.22.38;
DE Flags: Precursor;
GN Name=CTSK;
OS Macaca mulatta (Rhesus macaque).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini;
OC Cercopithecidae; Cercopithecinae; Macaca.
OX NCBI_TaxID=9544;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RX PubMed=10456386; DOI=10.1016/s8756-3282(99)00160-x;
RA Guay J., Riendeau D., Mancini J.A.;
RT "Cloning and expression of rhesus monkey cathepsin K.";
RL Bone 25:205-209(1999).
RN [2]
RP X-RAY CRYSTALLOGRAPHY (2.55 ANGSTROMS) OF 115-329 IN COMPLEX WITH
RP INHIBITORS, AND DISULFIDE BONDS.
RX PubMed=16509577; DOI=10.1021/jm050915u;
RA Yamashita D.S., Marquis R.W., Xie R., Nidamarthy S.D., Oh H.J., Jeong J.U.,
RA Erhard K.F., Ward K.W., Roethke T.J., Smith B.R., Cheng H.Y., Geng X.,
RA Lin F., Offen P.H., Wang B., Nevins N., Head M.S., Haltiwanger R.C.,
RA Narducci Sarjeant A.A., Liable-Sands L.M., Zhao B., Smith W.W.,
RA Janson C.A., Gao E., Tomaszek T., McQueney M., James I.E., Gress C.J.,
RA Zembryki D.L., Lark M.W., Veber D.F.;
RT "Structure activity relationships of 5-, 6-, and 7-methyl-substituted
RT azepan-3-one cathepsin K inhibitors.";
RL J. Med. Chem. 49:1597-1612(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 -!- 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; AF124092; AAD33249.1; -; mRNA.
DR RefSeq; NP_001027984.1; NM_001032812.2.
DR PDB; 2FTD; X-ray; 2.55 A; A/B=115-329.
DR PDBsum; 2FTD; -.
DR AlphaFoldDB; P61277; -.
DR SMR; P61277; -.
DR STRING; 9544.ENSMMUP00000000728; -.
DR MEROPS; I29.007; -.
DR PRIDE; P61277; -.
DR GeneID; 574112; -.
DR KEGG; mcc:574112; -.
DR CTD; 1513; -.
DR eggNOG; KOG1543; Eukaryota.
DR HOGENOM; CLU_012184_1_2_1; -.
DR InParanoid; P61277; -.
DR OMA; PVGNEKA; -.
DR TreeFam; TF313739; -.
DR EvolutionaryTrace; P61277; -.
DR Proteomes; UP000006718; Unplaced.
DR GO; GO:0016324; C:apical plasma membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0005615; C:extracellular space; ISS:UniProtKB.
DR GO; GO:0005764; C:lysosome; ISS:UniProtKB.
DR GO; GO:0004197; F:cysteine-type endopeptidase activity; IBA:GO_Central.
DR GO; GO:0006955; P:immune response; IBA:GO_Central.
DR GO; GO:0051603; P:proteolysis involved in protein catabolic process; IBA:GO_Central.
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_0000026299"
FT CHAIN 115..329
FT /note="Cathepsin K"
FT /id="PRO_0000026300"
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 DISULFID 136..177
FT /evidence="ECO:0000269|PubMed:16509577"
FT DISULFID 170..210
FT /evidence="ECO:0000269|PubMed:16509577"
FT DISULFID 269..318
FT /evidence="ECO:0000269|PubMed:16509577"
FT HELIX 121..124
FT /evidence="ECO:0007829|PDB:2FTD"
FT STRAND 135..137
FT /evidence="ECO:0007829|PDB:2FTD"
FT HELIX 139..156
FT /evidence="ECO:0007829|PDB:2FTD"
FT HELIX 164..170
FT /evidence="ECO:0007829|PDB:2FTD"
FT HELIX 176..178
FT /evidence="ECO:0007829|PDB:2FTD"
FT HELIX 182..192
FT /evidence="ECO:0007829|PDB:2FTD"
FT STRAND 195..197
FT /evidence="ECO:0007829|PDB:2FTD"
FT TURN 198..200
FT /evidence="ECO:0007829|PDB:2FTD"
FT HELIX 214..216
FT /evidence="ECO:0007829|PDB:2FTD"
FT STRAND 217..219
FT /evidence="ECO:0007829|PDB:2FTD"
FT STRAND 222..226
FT /evidence="ECO:0007829|PDB:2FTD"
FT HELIX 232..241
FT /evidence="ECO:0007829|PDB:2FTD"
FT STRAND 245..249
FT /evidence="ECO:0007829|PDB:2FTD"
FT HELIX 254..257
FT /evidence="ECO:0007829|PDB:2FTD"
FT STRAND 261..264
FT /evidence="ECO:0007829|PDB:2FTD"
FT STRAND 276..288
FT /evidence="ECO:0007829|PDB:2FTD"
FT STRAND 290..295
FT /evidence="ECO:0007829|PDB:2FTD"
FT STRAND 307..311
FT /evidence="ECO:0007829|PDB:2FTD"
FT STRAND 313..316
FT /evidence="ECO:0007829|PDB:2FTD"
FT HELIX 317..319
FT /evidence="ECO:0007829|PDB:2FTD"
FT STRAND 325..328
FT /evidence="ECO:0007829|PDB:2FTD"
SQ SEQUENCE 329 AA; 36942 MW; 652DD8DFC37FB984 CRC64;
MWGLKVLLLP VMSFALYPEE ILDTHWELWK KTHRKQYNSK VDEISRRLIW EKNLKYISIH
NLEASLGVHT YELAMNHLGD MTNEEVVQKM TGLKVPASHS RSNDTLYIPD WEGRAPDSVD
YRKKGYVTPV KNQGQCGSCW AFSSVGALEG QLKKKTGKLL NLSPQNLVDC VSENDGCGGG
YMTNAFQYVQ KNRGIDSEDA YPYVGQEESC MYNPTGKAAK CRGYREIPEG NEKALKRAVA
RVGPVSVAID ASLTSFQFYS KGVYYDESCN SDNLNHAVLA VGYGIQKGNK HWIIKNSWGE
NWGNKGYILM ARNKNNACGI ANLASFPKM
