P43235 (CATK_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Cathepsin K
EC=3.4.22.38

Alternative name(s):
Cathepsin O
Cathepsin O2
Cathepsin X

Gene names

Name:	CTSK
Synonyms:	CTSO, CTSO2

Organism

Homo sapiens (Human) [Reference proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Primates › Haplorrhini › Simiiformes › Catarrhini › Hominoidea › Hominidae › Homininae › Homo

Protein attributes

Sequence length	329 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is further processed into a mature form.
Protein existence	Evidence 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 component	Lysosome
Disease	Disease mutation
Domain	Signal
Molecular function	Hydrolase Protease Thiol protease
PTM	Disulfide bond Glycoprotein Zymogen
Technical term	3D-structure Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	bone resorption Inferred from electronic annotation. Source: Compara innate immune response Traceable author statement. Source: Reactome intramembranous ossification Inferred from electronic annotation. Source: Compara proteolysis Traceable author statement Ref.2. Source: ProtInc
Cellular_component	endolysosome lumen Traceable author statement. Source: Reactome extracellular space Inferred from electronic annotation. Source: Compara
Molecular_function	cysteine-type endopeptidase activity Traceable author statement PubMed 9143502. Source: ProtInc
Complete GO annotation...

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Signal peptide

1 – 15

15

Potential

Propeptide

16 – 114

99

Activation peptide

PRO_0000026295

Chain

115 – 329

215

Cathepsin K

PRO_0000026296

Sites

Active site

139

1

By similarity

Active site

276

1

By similarity

Active site

296

1

By similarity

Amino acid modifications

Glycosylation

103

1

N-linked (GlcNAc...) Potential

Disulfide bond

136 ↔ 177

Disulfide bond

170 ↔ 210

Disulfide bond

269 ↔ 318

Natural variations

Natural variant

79

1

G → E in PKND. Ref.15 Ref.16

VAR_015738

Natural variant

146

1

G → R in PKND. Ref.13

VAR_006725

Natural variant

277

1

A → V in PKND. Ref.14

VAR_015739

Natural variant

309

1

L → P in PKND. Ref.16
Corresponds to variant rs29001685 [ dbSNP | Ensembl ].

VAR_006726

Experimental info

Sequence conflict

46

1

R → P in AAA95998. Ref.3

Secondary structure

1

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329

Helix Strand Turn

Details...

Helix

22 – 32

11

Helix

40 – 66

27

Beta strand

70 – 73

4

Beta strand

79 – 81

3

Helix

83 – 89

7

Beta strand

102 – 107

6

Turn

121 – 125

5

Beta strand

135 – 137

3

Helix

139 – 156

18

Helix

164 – 170

7

Helix

176 – 178

3

Helix

182 – 192

11

Beta strand

195 – 197

3

Turn

198 – 200

3

Helix

214 – 216

3

Beta strand

217 – 219

3

Beta strand

224 – 226

3

Helix

232 – 241

10

Beta strand

245 – 249

5

Helix

254 – 257

4

Beta strand

261 – 264

4

Beta strand

276 – 286

11

Beta strand

289 – 295

7

Beta strand

300 – 302

3

Turn

303 – 305

3

Beta strand

307 – 316

10

Helix

317 – 319

3

Turn

320 – 322

3

Beta strand

325 – 327

3

Sequences

	Sequence		Length	Mass (Da)
	P43235 [UniParc]. Last modified November 1, 1995. Version 1. Checksum: 4677C3C89FF4CE85	FASTA	329	36,966
	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

References

	« Hide 'large scale' referencesShow '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. , 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. , 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. , 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.

Web resources

GeneReviews

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.

IPI

IPI00300599.

PIR

JC2476.

RefSeq

NP_000387.1. NM_000396.3.

UniGene

Hs.632466.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
1ATK	X-ray	2.20	A	115-329	[»]
1AU0	X-ray	2.60	A	115-329	[»]
1AU2	X-ray	2.60	A	115-329	[»]
1AU3	X-ray	2.50	A	115-329	[»]
1AU4	X-ray	2.30	A	115-329	[»]
1AYU	X-ray	2.20	A	115-329	[»]
1AYV	X-ray	2.30	A	115-329	[»]
1AYW	X-ray	2.40	A	115-329	[»]
1BGO	X-ray	2.30	A	115-329	[»]
1BY8	X-ray	2.60	A	16-329	[»]
1MEM	X-ray	1.80	A	115-329	[»]
1NL6	X-ray	2.80	A/B	115-329	[»]
1NLJ	X-ray	2.40	A/B	115-329	[»]
1Q6K	X-ray	2.10	A	115-329	[»]
1SNK	X-ray	2.40	A	116-329	[»]
1TU6	X-ray	1.75	A/B	115-329	[»]
1U9V	X-ray	2.20	A	113-329	[»]
1U9W	X-ray	2.30	A	113-329	[»]
1U9X	X-ray	2.10	A	113-329	[»]
1VSN	X-ray	2.00	A	115-329	[»]
1YK7	X-ray	2.50	A	115-329	[»]
1YK8	X-ray	2.60	A	115-329	[»]
1YT7	X-ray	2.30	A	115-329	[»]
2ATO	X-ray	2.00	A	115-329	[»]
2AUX	X-ray	2.40	A	115-329	[»]
2AUZ	X-ray	2.30	A	115-329	[»]
2BDL	X-ray	2.00	A	115-329	[»]
2R6N	X-ray	1.95	A	113-329	[»]
3C9E	X-ray	1.80	A	115-329	[»]
3H7D	X-ray	2.24	A/E	115-329	[»]
3KW9	X-ray	1.80	A	115-329	[»]
3KWB	X-ray	2.02	X/Y	115-329	[»]
3KWZ	X-ray	1.49	A	115-329	[»]
3KX1	X-ray	1.51	A	115-329	[»]
3O0U	X-ray	1.80	A	115-329	[»]
3O1G	X-ray	1.65	A	115-329	[»]
3OVZ	X-ray	2.02	A	121-329	[»]
4DMX	X-ray	1.70	A	115-329	[»]
4DMY	X-ray	1.63	A/B	115-329	[»]
7PCK	X-ray	3.20	A/B/C/D	16-329	[»]

ProteinModelPortal

P43235.

ModBase

Search...

Protein-protein interaction databases

DIP

DIP-39993N.

IntAct

P43235. 3 interactions.

STRING

9606.ENSP00000271651.

Protein family/group databases

MEROPS

I29.007.

PTM databases

PhosphoSite

P43235.

Polymorphism databases

DMDM

1168793.

Proteomic databases

PaxDb

P43235.

PRIDE

P43235.

Protocols and materials databases

DNASU

1513.

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENST00000271651; ENSP00000271651; ENSG00000143387.

GeneID

1513.

KEGG

hsa:1513.

UCSC

uc001evp.2. human.

Organism-specific databases

CTD

1513.

GeneCards

GC01M150768.

HGNC

HGNC:2536. CTSK.

MIM

265800. phenotype.
601105. gene.

neXtProt

NX_P43235.

Orphanet

763. Pycnodysostosis.

PharmGKB

PA27034.

GenAtlas

Search...

Phylogenomic databases

eggNOG

COG4870.

HOGENOM

HOG000230774.

HOVERGEN

HBG011513.

InParanoid

P43235.

KO

K01371.

OMA

LKVPPSH.

OrthoDB

EOG4SJ5FC.

PhylomeDB

P43235.

Enzyme and pathway databases

Reactome

REACT_118779. Extracellular matrix organization.
REACT_6900. Immune System.

Gene expression databases

ArrayExpress

P43235.

Bgee

P43235.

CleanEx

HS_CTSK.
HS_CTSO.

Genevestigator

P43235.

GermOnline

ENSG00000143387. Homo sapiens.

Family and domain databases

InterPro

IPR025661. 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]

PANTHER

PTHR12411. PTHR12411. 1 hit.
PTHR12411:SF55. PTHR12411:SF55. 1 hit.

Pfam

PF08246. Inhibitor_I29. 1 hit.
PF00112. Peptidase_C1. 1 hit.
[Graphical view]

PRINTS

PR00705. PAPAIN.

SMART

SM00848. Inhibitor_I29. 1 hit.
SM00645. Pept_C1. 1 hit.
[Graphical view]

PROSITE

PS00640. THIOL_PROTEASE_ASN. 1 hit.
PS00139. THIOL_PROTEASE_CYS. 1 hit.
PS00639. THIOL_PROTEASE_HIS. 1 hit.
[Graphical view]

ProtoNet

Search...

Other

BindingDB

P43235.

ChEMBL

CHEMBL268.

EvolutionaryTrace

P43235.

GenomeRNAi

1513.

NextBio

6267.

SOURCE

Search...

Entry information

Entry name

CATK_HUMAN

Accession

Primary (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:	May 1, 2013
This is version 141 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program

Disclaimer

Any 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.