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Protein

Cathepsin K

Gene

CTSK

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

Closely involved in osteoclastic bone resorption and may participate partially in the disorder of bone remodeling. Displays potent endoprotease activity against fibrinogen at acid pH. May play an important role in extracellular matrix degradation.

Catalytic activityi

Broad proteolytic activity. With small-molecule substrates and inhibitors, the major determinant of specificity is P2, which is preferably Leu, Met > Phe, and not Arg.

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Active sitei139By similarity1
Active sitei276By similarity1
Active sitei296By similarity1

GO - Molecular functioni

  • collagen binding Source: BHF-UCL
  • cysteine-type endopeptidase activity Source: BHF-UCL
  • cysteine-type peptidase activity Source: ProtInc
  • fibronectin binding Source: BHF-UCL
  • proteoglycan binding Source: BHF-UCL
  • serine-type endopeptidase activity Source: Reactome

GO - Biological processi

  • bone resorption Source: Ensembl
  • collagen catabolic process Source: BHF-UCL
  • extracellular matrix disassembly Source: Reactome
  • intramembranous ossification Source: Ensembl
  • positive regulation of protein targeting to mitochondrion Source: ParkinsonsUK-UCL
  • proteolysis Source: ProtInc
  • proteolysis involved in cellular protein catabolic process Source: BHF-UCL
  • regulation of mitophagy Source: ParkinsonsUK-UCL
  • toll-like receptor signaling pathway Source: Reactome
Complete GO annotation...

Keywords - Molecular functioni

Hydrolase, Protease, Thiol protease

Enzyme and pathway databases

BioCyciZFISH:HS07044-MONOMER.
BRENDAi3.4.22.38. 2681.
ReactomeiR-HSA-1442490. Collagen degradation.
R-HSA-1474228. Degradation of the extracellular matrix.
R-HSA-1592389. Activation of Matrix Metalloproteinases.
R-HSA-1679131. Trafficking and processing of endosomal TLR.
R-HSA-2132295. MHC class II antigen presentation.
SIGNORiP43235.

Protein family/group databases

MEROPSiI29.007.

Names & Taxonomyi

Protein namesi
Recommended name:
Cathepsin K (EC:3.4.22.38)
Alternative name(s):
Cathepsin O
Cathepsin O2
Cathepsin X
Gene namesi
Name:CTSK
Synonyms:CTSO, CTSO2
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 1

Organism-specific databases

HGNCiHGNC:2536. CTSK.

Subcellular locationi

GO - Cellular componenti

  • endolysosome lumen Source: Reactome
  • extracellular region Source: Reactome
  • extracellular space Source: BHF-UCL
  • lysosome Source: GO_Central
Complete GO annotation...

Keywords - Cellular componenti

Lysosome

Pathology & Biotechi

Involvement in diseasei

Pycnodysostosis (PKND)6 Publications
The disease is caused by mutations affecting the gene represented in this entry.
Disease descriptionA rare autosomal recessive bone disorder characterized by deformity of the skull, maxilla and phalanges, osteosclerosis, and fragility of bone.
See also OMIM:265800
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_01573879G → E in PKND. 2 PublicationsCorresponds to variant rs74315305dbSNPEnsembl.1
Natural variantiVAR_074023122R → P in PKND. 1 Publication1
Natural variantiVAR_006725146G → R in PKND. 1 PublicationCorresponds to variant rs74315302dbSNPEnsembl.1
Natural variantiVAR_015739277A → V in PKND. 2 PublicationsCorresponds to variant rs74315304dbSNPEnsembl.1
Natural variantiVAR_074024283Y → C in PKND; does not affect protein level; does not detect cysteine-type endopeptidase activity. 1 Publication1
Natural variantiVAR_006726309L → P in PKND. 1 PublicationCorresponds to variant rs29001685dbSNPEnsembl.1

Keywords - Diseasei

Disease mutation

Organism-specific databases

DisGeNETi1513.
MalaCardsiCTSK.
MIMi265800. phenotype.
OpenTargetsiENSG00000143387.
Orphaneti763. Pycnodysostosis.
PharmGKBiPA27034.

Chemistry databases

ChEMBLiCHEMBL268.
GuidetoPHARMACOLOGYi2350.

Polymorphism and mutation databases

BioMutaiCTSK.
DMDMi1168793.

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Signal peptidei1 – 15Sequence analysisAdd BLAST15
PropeptideiPRO_000002629516 – 114Activation peptideAdd BLAST99
ChainiPRO_0000026296115 – 329Cathepsin KAdd BLAST215

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Glycosylationi103N-linked (GlcNAc...)Sequence analysis1
Disulfide bondi136 ↔ 177
Disulfide bondi170 ↔ 210
Disulfide bondi269 ↔ 318

Keywords - PTMi

Disulfide bond, Glycoprotein, Zymogen

Proteomic databases

EPDiP43235.
PaxDbiP43235.
PeptideAtlasiP43235.
PRIDEiP43235.

PTM databases

iPTMnetiP43235.
PhosphoSitePlusiP43235.

Expressioni

Tissue specificityi

Predominantly expressed in osteoclasts (bones).

Gene expression databases

BgeeiENSG00000143387.
CleanExiHS_CTSK.
HS_CTSO.
ExpressionAtlasiP43235. baseline and differential.
GenevisibleiP43235. HS.

Organism-specific databases

HPAiCAB013634.

Interactioni

GO - Molecular functioni

  • collagen binding Source: BHF-UCL
  • fibronectin binding Source: BHF-UCL

Protein-protein interaction databases

BioGridi107893. 8 interactors.
DIPiDIP-39993N.
IntActiP43235. 3 interactors.
STRINGi9606.ENSP00000271651.

Chemistry databases

BindingDBiP43235.

Structurei

Secondary structure

1329
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Helixi22 – 32Combined sources11
Helixi40 – 66Combined sources27
Beta strandi70 – 73Combined sources4
Beta strandi79 – 81Combined sources3
Helixi83 – 89Combined sources7
Beta strandi102 – 107Combined sources6
Helixi121 – 124Combined sources4
Beta strandi135 – 137Combined sources3
Helixi139 – 156Combined sources18
Helixi164 – 170Combined sources7
Helixi176 – 178Combined sources3
Helixi182 – 192Combined sources11
Beta strandi195 – 197Combined sources3
Turni198 – 200Combined sources3
Helixi214 – 216Combined sources3
Beta strandi217 – 219Combined sources3
Beta strandi223 – 226Combined sources4
Helixi232 – 242Combined sources11
Beta strandi245 – 249Combined sources5
Helixi254 – 257Combined sources4
Beta strandi261 – 264Combined sources4
Beta strandi276 – 286Combined sources11
Beta strandi289 – 295Combined sources7
Beta strandi300 – 302Combined sources3
Turni303 – 305Combined sources3
Beta strandi307 – 316Combined sources10
Helixi317 – 319Combined sources3
Turni320 – 322Combined sources3
Beta strandi325 – 328Combined sources4

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
1ATKX-ray2.20A115-329[»]
1AU0X-ray2.60A115-329[»]
1AU2X-ray2.60A115-329[»]
1AU3X-ray2.50A115-329[»]
1AU4X-ray2.30A115-329[»]
1AYUX-ray2.20A115-329[»]
1AYVX-ray2.30A115-329[»]
1AYWX-ray2.40A115-329[»]
1BGOX-ray2.30A115-329[»]
1BY8X-ray2.60A16-329[»]
1MEMX-ray1.80A115-329[»]
1NL6X-ray2.80A/B115-329[»]
1NLJX-ray2.40A/B115-329[»]
1Q6KX-ray2.10A115-329[»]
1SNKX-ray2.40A116-329[»]
1TU6X-ray1.75A/B115-329[»]
1U9VX-ray2.20A113-329[»]
1U9WX-ray2.30A113-329[»]
1U9XX-ray2.10A113-329[»]
1VSNX-ray2.00A115-329[»]
1YK7X-ray2.50A115-329[»]
1YK8X-ray2.60A115-329[»]
1YT7X-ray2.30A115-329[»]
2ATOX-ray2.00A115-329[»]
2AUXX-ray2.40A115-329[»]
2AUZX-ray2.30A115-329[»]
2BDLX-ray2.00A115-329[»]
2R6NX-ray1.95A113-329[»]
3C9EX-ray1.80A115-329[»]
3H7DX-ray2.24A/E115-329[»]
3KW9X-ray1.80A115-329[»]
3KWBX-ray2.02X/Y115-329[»]
3KWZX-ray1.49A115-329[»]
3KX1X-ray1.51A115-329[»]
3O0UX-ray1.80A115-329[»]
3O1GX-ray1.65A115-329[»]
3OVZX-ray2.02A121-329[»]
4DMXX-ray1.70A115-329[»]
4DMYX-ray1.63A/B115-329[»]
4N79X-ray2.62A115-329[»]
4N8WX-ray2.02A115-329[»]
4X6HX-ray1.00A115-329[»]
4X6IX-ray1.87A115-329[»]
4X6JX-ray1.59A115-329[»]
4YV8X-ray2.00A115-329[»]
4YVAX-ray1.80A115-329[»]
5J94X-ray2.60A107-329[»]
7PCKX-ray3.20A/B/C/D16-329[»]
ProteinModelPortaliP43235.
SMRiP43235.
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiP43235.

Family & Domainsi

Sequence similaritiesi

Belongs to the peptidase C1 family.PROSITE-ProRule annotation

Keywords - Domaini

Signal

Phylogenomic databases

eggNOGiKOG1543. Eukaryota.
COG4870. LUCA.
GeneTreeiENSGT00760000118871.
HOGENOMiHOG000230774.
HOVERGENiHBG011513.
InParanoidiP43235.
KOiK01371.
OMAiKHISIHN.
OrthoDBiEOG091G0AKT.
PhylomeDBiP43235.
TreeFamiTF313739.

Family and domain databases

InterProiIPR025661. Pept_asp_AS.
IPR000169. Pept_cys_AS.
IPR025660. Pept_his_AS.
IPR013128. Peptidase_C1A.
IPR000668. Peptidase_C1A_C.
IPR015644. Peptidase_C1A_cathepsin-K.
IPR013201. Prot_inhib_I29.
[Graphical view]
PANTHERiPTHR12411. PTHR12411. 1 hit.
PTHR12411:SF55. PTHR12411:SF55. 1 hit.
PfamiPF08246. Inhibitor_I29. 1 hit.
PF00112. Peptidase_C1. 1 hit.
[Graphical view]
PRINTSiPR00705. PAPAIN.
SMARTiSM00848. Inhibitor_I29. 1 hit.
SM00645. Pept_C1. 1 hit.
[Graphical view]
PROSITEiPS00640. THIOL_PROTEASE_ASN. 1 hit.
PS00139. THIOL_PROTEASE_CYS. 1 hit.
PS00639. THIOL_PROTEASE_HIS. 1 hit.
[Graphical view]

Sequencei

Sequence statusi: Complete.

Sequence processingi: The displayed sequence is further processed into a mature form.

P43235-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MWGLKVLLLP VVSFALYPEE ILDTHWELWK KTHRKQYNNK VDEISRRLIW
60 70 80 90 100
EKNLKYISIH NLEASLGVHT YELAMNHLGD MTSEEVVQKM TGLKVPLSHS
110 120 130 140 150
RSNDTLYIPE WEGRAPDSVD YRKKGYVTPV KNQGQCGSCW AFSSVGALEG
160 170 180 190 200
QLKKKTGKLL NLSPQNLVDC VSENDGCGGG YMTNAFQYVQ KNRGIDSEDA
210 220 230 240 250
YPYVGQEESC MYNPTGKAAK CRGYREIPEG NEKALKRAVA RVGPVSVAID
260 270 280 290 300
ASLTSFQFYS KGVYYDESCN SDNLNHAVLA VGYGIQKGNK HWIIKNSWGE
310 320
NWGNKGYILM ARNKNNACGI ANLASFPKM
Length:329
Mass (Da):36,966
Last modified:November 1, 1995 - v1
Checksum:i4677C3C89FF4CE85
GO

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti46R → P in AAA95998 (PubMed:8585423).Curated1

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_01573879G → E in PKND. 2 PublicationsCorresponds to variant rs74315305dbSNPEnsembl.1
Natural variantiVAR_074023122R → P in PKND. 1 Publication1
Natural variantiVAR_006725146G → R in PKND. 1 PublicationCorresponds to variant rs74315302dbSNPEnsembl.1
Natural variantiVAR_015739277A → V in PKND. 2 PublicationsCorresponds to variant rs74315304dbSNPEnsembl.1
Natural variantiVAR_074024283Y → C in PKND; does not affect protein level; does not detect cysteine-type endopeptidase activity. 1 Publication1
Natural variantiVAR_006726309L → P in PKND. 1 PublicationCorresponds to variant rs29001685dbSNPEnsembl.1

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
U13665 mRNA. Translation: AAA65233.1.
X82153 mRNA. Translation: CAA57649.1.
U20280 mRNA. Translation: AAA95998.1.
S79895 mRNA. Translation: AAB35521.1.
CR541675 mRNA. Translation: CAG46476.1.
AL355860, AL356292 Genomic DNA. Translation: CAI12795.1.
AL356292, AL355860 Genomic DNA. Translation: CAI13649.1.
CH471121 Genomic DNA. Translation: EAW53516.1.
BC016058 mRNA. Translation: AAH16058.1.
CCDSiCCDS969.1.
PIRiJC2476.
RefSeqiNP_000387.1. NM_000396.3.
UniGeneiHs.632466.

Genome annotation databases

EnsembliENST00000271651; ENSP00000271651; ENSG00000143387.
GeneIDi1513.
KEGGihsa:1513.
UCSCiuc001evp.3. human.

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
U13665 mRNA. Translation: AAA65233.1.
X82153 mRNA. Translation: CAA57649.1.
U20280 mRNA. Translation: AAA95998.1.
S79895 mRNA. Translation: AAB35521.1.
CR541675 mRNA. Translation: CAG46476.1.
AL355860, AL356292 Genomic DNA. Translation: CAI12795.1.
AL356292, AL355860 Genomic DNA. Translation: CAI13649.1.
CH471121 Genomic DNA. Translation: EAW53516.1.
BC016058 mRNA. Translation: AAH16058.1.
CCDSiCCDS969.1.
PIRiJC2476.
RefSeqiNP_000387.1. NM_000396.3.
UniGeneiHs.632466.

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
1ATKX-ray2.20A115-329[»]
1AU0X-ray2.60A115-329[»]
1AU2X-ray2.60A115-329[»]
1AU3X-ray2.50A115-329[»]
1AU4X-ray2.30A115-329[»]
1AYUX-ray2.20A115-329[»]
1AYVX-ray2.30A115-329[»]
1AYWX-ray2.40A115-329[»]
1BGOX-ray2.30A115-329[»]
1BY8X-ray2.60A16-329[»]
1MEMX-ray1.80A115-329[»]
1NL6X-ray2.80A/B115-329[»]
1NLJX-ray2.40A/B115-329[»]
1Q6KX-ray2.10A115-329[»]
1SNKX-ray2.40A116-329[»]
1TU6X-ray1.75A/B115-329[»]
1U9VX-ray2.20A113-329[»]
1U9WX-ray2.30A113-329[»]
1U9XX-ray2.10A113-329[»]
1VSNX-ray2.00A115-329[»]
1YK7X-ray2.50A115-329[»]
1YK8X-ray2.60A115-329[»]
1YT7X-ray2.30A115-329[»]
2ATOX-ray2.00A115-329[»]
2AUXX-ray2.40A115-329[»]
2AUZX-ray2.30A115-329[»]
2BDLX-ray2.00A115-329[»]
2R6NX-ray1.95A113-329[»]
3C9EX-ray1.80A115-329[»]
3H7DX-ray2.24A/E115-329[»]
3KW9X-ray1.80A115-329[»]
3KWBX-ray2.02X/Y115-329[»]
3KWZX-ray1.49A115-329[»]
3KX1X-ray1.51A115-329[»]
3O0UX-ray1.80A115-329[»]
3O1GX-ray1.65A115-329[»]
3OVZX-ray2.02A121-329[»]
4DMXX-ray1.70A115-329[»]
4DMYX-ray1.63A/B115-329[»]
4N79X-ray2.62A115-329[»]
4N8WX-ray2.02A115-329[»]
4X6HX-ray1.00A115-329[»]
4X6IX-ray1.87A115-329[»]
4X6JX-ray1.59A115-329[»]
4YV8X-ray2.00A115-329[»]
4YVAX-ray1.80A115-329[»]
5J94X-ray2.60A107-329[»]
7PCKX-ray3.20A/B/C/D16-329[»]
ProteinModelPortaliP43235.
SMRiP43235.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi107893. 8 interactors.
DIPiDIP-39993N.
IntActiP43235. 3 interactors.
STRINGi9606.ENSP00000271651.

Chemistry databases

BindingDBiP43235.
ChEMBLiCHEMBL268.
GuidetoPHARMACOLOGYi2350.

Protein family/group databases

MEROPSiI29.007.

PTM databases

iPTMnetiP43235.
PhosphoSitePlusiP43235.

Polymorphism and mutation databases

BioMutaiCTSK.
DMDMi1168793.

Proteomic databases

EPDiP43235.
PaxDbiP43235.
PeptideAtlasiP43235.
PRIDEiP43235.

Protocols and materials databases

DNASUi1513.
Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000271651; ENSP00000271651; ENSG00000143387.
GeneIDi1513.
KEGGihsa:1513.
UCSCiuc001evp.3. human.

Organism-specific databases

CTDi1513.
DisGeNETi1513.
GeneCardsiCTSK.
HGNCiHGNC:2536. CTSK.
HPAiCAB013634.
MalaCardsiCTSK.
MIMi265800. phenotype.
601105. gene.
neXtProtiNX_P43235.
OpenTargetsiENSG00000143387.
Orphaneti763. Pycnodysostosis.
PharmGKBiPA27034.
GenAtlasiSearch...

Phylogenomic databases

eggNOGiKOG1543. Eukaryota.
COG4870. LUCA.
GeneTreeiENSGT00760000118871.
HOGENOMiHOG000230774.
HOVERGENiHBG011513.
InParanoidiP43235.
KOiK01371.
OMAiKHISIHN.
OrthoDBiEOG091G0AKT.
PhylomeDBiP43235.
TreeFamiTF313739.

Enzyme and pathway databases

BioCyciZFISH:HS07044-MONOMER.
BRENDAi3.4.22.38. 2681.
ReactomeiR-HSA-1442490. Collagen degradation.
R-HSA-1474228. Degradation of the extracellular matrix.
R-HSA-1592389. Activation of Matrix Metalloproteinases.
R-HSA-1679131. Trafficking and processing of endosomal TLR.
R-HSA-2132295. MHC class II antigen presentation.
SIGNORiP43235.

Miscellaneous databases

ChiTaRSiCTSK. human.
EvolutionaryTraceiP43235.
GeneWikiiCathepsin_K.
GenomeRNAii1513.
PROiP43235.
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000143387.
CleanExiHS_CTSK.
HS_CTSO.
ExpressionAtlasiP43235. baseline and differential.
GenevisibleiP43235. HS.

Family and domain databases

InterProiIPR025661. Pept_asp_AS.
IPR000169. Pept_cys_AS.
IPR025660. Pept_his_AS.
IPR013128. Peptidase_C1A.
IPR000668. Peptidase_C1A_C.
IPR015644. Peptidase_C1A_cathepsin-K.
IPR013201. Prot_inhib_I29.
[Graphical view]
PANTHERiPTHR12411. PTHR12411. 1 hit.
PTHR12411:SF55. PTHR12411:SF55. 1 hit.
PfamiPF08246. Inhibitor_I29. 1 hit.
PF00112. Peptidase_C1. 1 hit.
[Graphical view]
PRINTSiPR00705. PAPAIN.
SMARTiSM00848. Inhibitor_I29. 1 hit.
SM00645. Pept_C1. 1 hit.
[Graphical view]
PROSITEiPS00640. THIOL_PROTEASE_ASN. 1 hit.
PS00139. THIOL_PROTEASE_CYS. 1 hit.
PS00639. THIOL_PROTEASE_HIS. 1 hit.
[Graphical view]
ProtoNetiSearch...

Entry informationi

Entry nameiCATK_HUMAN
AccessioniPrimary (citable) accession number: P43235
Secondary accession number(s): Q6FHS6
Entry historyi
Integrated into UniProtKB/Swiss-Prot: November 1, 1995
Last sequence update: November 1, 1995
Last modified: November 2, 2016
This is version 175 of the entry and version 1 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

Miscellaneousi

Keywords - Technical termi

3D-structure, Complete proteome, Reference proteome

Documents

  1. Human chromosome 1
    Human chromosome 1: entries, gene names and cross-references to MIM
  2. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  3. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  4. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  5. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  6. Peptidase families
    Classification of peptidase families and list of entries
  7. SIMILARITY comments
    Index of protein domains and families

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.