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P43235 (CATK_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified July 9, 2014. Version 153. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (7) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Cathepsin K

EC=3.4.22.38
Alternative name(s):
Cathepsin O
Cathepsin O2
Cathepsin X
Gene names
Name:CTSK
Synonyms:CTSO, CTSO2
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length329 AA.
Sequence statusComplete.
Sequence processingThe displayed sequence is further processed into a mature form.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

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 activity

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.

Subcellular location

Lysosome.

Tissue specificity

Predominantly expressed in osteoclasts (bones).

Involvement in disease

Pycnodysostosis (PKND) [MIM:265800]: A rare autosomal recessive bone disorder characterized by deformity of the skull, maxilla and phalanges, osteosclerosis, and fragility of bone.
Note: The disease is caused by mutations affecting the gene represented in this entry. Ref.13 Ref.14 Ref.15 Ref.16

Sequence similarities

Belongs to the peptidase C1 family.

Ontologies

Keywords
   Cellular componentLysosome
   DiseaseDisease mutation
   DomainSignal
   Molecular functionHydrolase
Protease
Thiol protease
   PTMDisulfide bond
Glycoprotein
Zymogen
   Technical term3D-structure
Complete proteome
Reference proteome
Gene Ontology (GO)
   Biological_processbone resorption

Inferred from electronic annotation. Source: Ensembl

collagen catabolic process

Inferred from direct assay PubMed 22952693. Source: BHF-UCL

extracellular matrix disassembly

Traceable author statement. Source: Reactome

extracellular matrix organization

Traceable author statement. Source: Reactome

innate immune response

Traceable author statement. Source: Reactome

intramembranous ossification

Inferred from electronic annotation. Source: Ensembl

proteolysis

Traceable author statement Ref.2. Source: ProtInc

proteolysis involved in cellular protein catabolic process

Inferred from direct assay PubMed 22952693. Source: BHF-UCL

toll-like receptor signaling pathway

Traceable author statement. Source: Reactome

   Cellular_componentendolysosome lumen

Traceable author statement. Source: Reactome

extracellular region

Traceable author statement. Source: Reactome

extracellular space

Inferred from direct assay PubMed 22952693. Source: BHF-UCL

   Molecular_functioncollagen binding

Inferred from direct assay PubMed 22952693. Source: BHF-UCL

cysteine-type endopeptidase activity

Inferred from direct assay PubMed 22952693. Source: BHF-UCL

cysteine-type peptidase activity

Traceable author statement Ref.2. Source: ProtInc

fibronectin binding

Inferred from physical interaction PubMed 22952693. Source: BHF-UCL

proteoglycan binding

Inferred from physical interaction PubMed 22952693. Source: BHF-UCL

Complete GO annotation...

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Signal peptide1 – 1515 Potential
Propeptide16 – 11499Activation peptide
PRO_0000026295
Chain115 – 329215Cathepsin K
PRO_0000026296

Sites

Active site1391 By similarity
Active site2761 By similarity
Active site2961 By similarity

Amino acid modifications

Glycosylation1031N-linked (GlcNAc...) Potential
Disulfide bond136 ↔ 177
Disulfide bond170 ↔ 210
Disulfide bond269 ↔ 318

Natural variations

Natural variant791G → E in PKND. Ref.15 Ref.16
VAR_015738
Natural variant1461G → R in PKND. Ref.13
VAR_006725
Natural variant2771A → V in PKND. Ref.14
VAR_015739
Natural variant3091L → P in PKND. Ref.16
Corresponds to variant rs29001685 [ dbSNP | Ensembl ].
VAR_006726

Experimental info

Sequence conflict461R → P in AAA95998. Ref.3

Secondary structure

........................................................ 329
Helix Strand Turn

Details...

Sequences

Sequence LengthMass (Da)Tools
P43235 [UniParc].

Last modified November 1, 1995. Version 1.
Checksum: 4677C3C89FF4CE85

FASTA32936,966
        10         20         30         40         50         60 
MWGLKVLLLP VVSFALYPEE ILDTHWELWK KTHRKQYNNK VDEISRRLIW EKNLKYISIH 

        70         80         90        100        110        120 
NLEASLGVHT YELAMNHLGD MTSEEVVQKM TGLKVPLSHS RSNDTLYIPE WEGRAPDSVD 

       130        140        150        160        170        180 
YRKKGYVTPV KNQGQCGSCW AFSSVGALEG QLKKKTGKLL NLSPQNLVDC VSENDGCGGG 

       190        200        210        220        230        240 
YMTNAFQYVQ KNRGIDSEDA YPYVGQEESC MYNPTGKAAK CRGYREIPEG NEKALKRAVA 

       250        260        270        280        290        300 
RVGPVSVAID ASLTSFQFYS KGVYYDESCN SDNLNHAVLA VGYGIQKGNK HWIIKNSWGE 

       310        320 
NWGNKGYILM ARNKNNACGI ANLASFPKM 

« Hide

References

« Hide 'large scale' references
[1]"Molecular cloning of human cathepsin O, a novel endoproteinase and homologue of rabbit OC2."
Shi G.-P., Chapman H.A., Bhairi S.M., Deleeuw C., Reddy V.Y., Weiss S.J.
FEBS Lett. 357:129-134(1995) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA].
Tissue: Blood.
[2]"Molecular cloning of human cDNA for cathepsin K: novel cysteine proteinase predominantly expressed in bone."
Inaoka T., Bilbe G., Ishibashi O., Tezuka K., Kumegawa M., Kokubo T.
Biochem. Biophys. Res. Commun. 206:89-96(1995) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA].
Tissue: Bone.
[3]"Cloning and complete coding sequence of a novel human cathepsin expressed in giant cells of osteoclastomas."
Li Y., Alexander M., Wucherpfennig A.L., Yelick P., Chen W., Stashenko P.
J. Bone Miner. Res. 10:1197-1202(1995) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA].
Tissue: Osteoclastoma.
[4]"Human cathepsin O2, a novel cysteine protease highly expressed in osteoclastomas and ovary molecular cloning, sequencing and tissue distribution."
Broemme D., Okamoto K.
Biol. Chem. Hoppe-Seyler 376:379-384(1995) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA].
Tissue: Spleen.
[5]"Cloning of human full open reading frames in Gateway(TM) system entry vector (pDONR201)."
Ebert L., Schick M., Neubert P., Schatten R., Henze S., Korn B.
Submitted (JUN-2004) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
[6]"The DNA sequence and biological annotation of human chromosome 1."
Gregory S.G., Barlow K.F., McLay K.E., Kaul R., Swarbreck D., Dunham A., Scott C.E., Howe K.L., Woodfine K., Spencer C.C.A., Jones M.C., Gillson C., Searle S., Zhou Y., Kokocinski F., McDonald L., Evans R., Phillips K. expand/collapse author list , Atkinson A., Cooper R., Jones C., Hall R.E., Andrews T.D., Lloyd C., Ainscough R., Almeida J.P., Ambrose K.D., Anderson F., Andrew R.W., Ashwell R.I.S., Aubin K., Babbage A.K., Bagguley C.L., Bailey J., Beasley H., Bethel G., Bird C.P., Bray-Allen S., Brown J.Y., Brown A.J., Buckley D., Burton J., Bye J., Carder C., Chapman J.C., Clark S.Y., Clarke G., Clee C., Cobley V., Collier R.E., Corby N., Coville G.J., Davies J., Deadman R., Dunn M., Earthrowl M., Ellington A.G., Errington H., Frankish A., Frankland J., French L., Garner P., Garnett J., Gay L., Ghori M.R.J., Gibson R., Gilby L.M., Gillett W., Glithero R.J., Grafham D.V., Griffiths C., Griffiths-Jones S., Grocock R., Hammond S., Harrison E.S.I., Hart E., Haugen E., Heath P.D., Holmes S., Holt K., Howden P.J., Hunt A.R., Hunt S.E., Hunter G., Isherwood J., James R., Johnson C., Johnson D., Joy A., Kay M., Kershaw J.K., Kibukawa M., Kimberley A.M., King A., Knights A.J., Lad H., Laird G., Lawlor S., Leongamornlert D.A., Lloyd D.M., Loveland J., Lovell J., Lush M.J., Lyne R., Martin S., Mashreghi-Mohammadi M., Matthews L., Matthews N.S.W., McLaren S., Milne S., Mistry S., Moore M.J.F., Nickerson T., O'Dell C.N., Oliver K., Palmeiri A., Palmer S.A., Parker A., Patel D., Pearce A.V., Peck A.I., Pelan S., Phelps K., Phillimore B.J., Plumb R., Rajan J., Raymond C., Rouse G., Saenphimmachak C., Sehra H.K., Sheridan E., Shownkeen R., Sims S., Skuce C.D., Smith M., Steward C., Subramanian S., Sycamore N., Tracey A., Tromans A., Van Helmond Z., Wall M., Wallis J.M., White S., Whitehead S.L., Wilkinson J.E., Willey D.L., Williams H., Wilming L., Wray P.W., Wu Z., Coulson A., Vaudin M., Sulston J.E., Durbin R.M., Hubbard T., Wooster R., Dunham I., Carter N.P., McVean G., Ross M.T., Harrow J., Olson M.V., Beck S., Rogers J., Bentley D.R.
Nature 441:315-321(2006) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[7]Mural R.J., Istrail S., Sutton G., Florea L., Halpern A.L., Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., Turner R. expand/collapse author list , Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W., Venter J.C.
Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[8]"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
The MGC Project Team
Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
Tissue: Skin.
[9]"Crystal structure of human cathepsin K complexed with a potent inhibitor."
McGrath M.E., Klaus J.L., Barnes M.G., Bromme D.
Nat. Struct. Biol. 4:105-109(1997) [PubMed] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (1.8 ANGSTROMS).
[10]"Design of potent and selective human cathepsin K inhibitors that span the active site."
Thompson S.K., Halbert S.M., Bossard M.J., Tomaszek T.A., Levy M.A., Zhao B., Smith W.W., Abdel-Meguid S.S., Janson C.A., D'Alessio K.J., McQueney M.S., Amegadzie B.Y., Hanning C.R., Desjarlais R.L., Briand J., Sarkar S.K., Huddleston M.J., Ijames C.F. expand/collapse author list , Carr S.A., Garnes K.T., Shu A., Heys J.R., Bradbeer J., Zembryki D., Veber D.F.
Proc. Natl. Acad. Sci. U.S.A. 94:14249-14254(1997) [PubMed] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (2.2 ANGSTROMS).
[11]"The crystal structure of human procathepsin K."
LaLonde J.M., Zhao B., Janson C.A., D'Alessio K.J., McQueney M.S., Orsini M.J., Debouck C.M., Smith W.W.
Biochemistry 38:862-869(1999) [PubMed] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (2.8 ANGSTROMS) OF ZYMOGEN FORM.
[12]"Crystal structure of wild-type human procathepsin K."
Sivaraman J., Lalumiere M., Menard R., Cygler M.
Protein Sci. 8:283-290(1999) [PubMed] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (3.2 ANGSTROMS).
[13]"Pycnodysostosis, a lysosomal disease caused by cathepsin K deficiency."
Gelb B.D., Shi G.-P., Chapman H.A., Desnick R.J.
Science 273:1236-1238(1996) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT PKND ARG-146.
[14]"Paternal uniparental disomy for chromosome 1 revealed by molecular analysis of a patient with pycnodysostosis."
Gelb B.D., Willner J.P., Dunn T.M., Kardon N.B., Verloes A., Poncin J., Desnick R.J.
Am. J. Hum. Genet. 62:848-854(1998) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT PKND VAL-277.
[15]"Mutations of CTSK result in pycnodysostosis via a reduction in cathepsin K protein."
Ho N., Punturieri A., Wilkin D., Szabo J., Johnson M., Whaley J., Davis J., Clark A., Weiss S., Francomano C.
J. Bone Miner. Res. 14:1649-1653(1999) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT PKND GLU-79.
[16]"Cathepsin K gene mutations and 1q21 haplotypes in at patients with pycnodysostosis in an outbred population."
Haagerup A., Hertz J.M., Christensen M.F., Binderup H., Kruse T.A.
Eur. J. Hum. Genet. 8:431-436(2000) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANTS PKND GLU-79 AND PRO-309.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
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.
CCDSCCDS969.1.
PIRJC2476.
RefSeqNP_000387.1. NM_000396.3.
UniGeneHs.632466.

3D structure databases

PDBe
RCSB-PDB
PDBj
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[»]
4LEGX-ray2.60A107-329[»]
7PCKX-ray3.20A/B/C/D16-329[»]
ProteinModelPortalP43235.
SMRP43235. Positions 16-329.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid107893. 3 interactions.
DIPDIP-39993N.
IntActP43235. 3 interactions.
STRING9606.ENSP00000271651.

Chemistry

BindingDBP43235.
ChEMBLCHEMBL2111361.
GuidetoPHARMACOLOGY2350.

Protein family/group databases

MEROPSC01.036.

PTM databases

PhosphoSiteP43235.

Polymorphism databases

DMDM1168793.

Proteomic databases

PaxDbP43235.
PRIDEP43235.

Protocols and materials databases

DNASU1513.
StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000271651; ENSP00000271651; ENSG00000143387.
GeneID1513.
KEGGhsa:1513.
UCSCuc001evp.2. human.

Organism-specific databases

CTD1513.
GeneCardsGC01M150768.
HGNCHGNC:2536. CTSK.
MIM265800. phenotype.
601105. gene.
neXtProtNX_P43235.
Orphanet763. Pycnodysostosis.
PharmGKBPA27034.
GenAtlasSearch...

Phylogenomic databases

eggNOGCOG4870.
HOGENOMHOG000230774.
HOVERGENHBG011513.
InParanoidP43235.
KOK01371.
OMAILDTQWE.
OrthoDBEOG786H3P.
PhylomeDBP43235.
TreeFamTF313739.

Enzyme and pathway databases

ReactomeREACT_118779. Extracellular matrix organization.
REACT_6900. Immune System.

Gene expression databases

ArrayExpressP43235.
BgeeP43235.
CleanExHS_CTSK.
HS_CTSO.
GenevestigatorP43235.

Family and domain databases

InterProIPR025661. 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]
PANTHERPTHR12411. PTHR12411. 1 hit.
PTHR12411:SF55. PTHR12411:SF55. 1 hit.
PfamPF08246. Inhibitor_I29. 1 hit.
PF00112. Peptidase_C1. 1 hit.
[Graphical view]
PRINTSPR00705. PAPAIN.
SMARTSM00848. Inhibitor_I29. 1 hit.
SM00645. Pept_C1. 1 hit.
[Graphical view]
PROSITEPS00640. THIOL_PROTEASE_ASN. 1 hit.
PS00139. THIOL_PROTEASE_CYS. 1 hit.
PS00639. THIOL_PROTEASE_HIS. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

EvolutionaryTraceP43235.
GeneWikiCathepsin_K.
GenomeRNAi1513.
NextBio6267.
PROP43235.
SOURCESearch...

Entry information

Entry nameCATK_HUMAN
AccessionPrimary (citable) accession number: P43235
Secondary accession number(s): Q6FHS6
Entry history
Integrated into UniProtKB/Swiss-Prot: November 1, 1995
Last sequence update: November 1, 1995
Last modified: July 9, 2014
This is version 153 of the entry and version 1 of the sequence. [Complete history]
Entry statusReviewed (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.

Relevant documents

SIMILARITY comments

Index of protein domains and families

Peptidase families

Classification of peptidase families and list of entries

PDB cross-references

Index of Protein Data Bank (PDB) cross-references

MIM cross-references

Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

Human polymorphisms and disease mutations

Index of human polymorphisms and disease mutations

Human entries with polymorphisms or disease mutations

List of human entries with polymorphisms or disease mutations

Human chromosome 1

Human chromosome 1: entries, gene names and cross-references to MIM