Cathepsin K precursor - Homo sapiens (Human)

Names and origin

Protein names

Recommended name:
    Cathepsin K
    EC=3.4.22.38
Alternative name(s):
    Cathepsin O
    Cathepsin X
    Cathepsin O2

Gene names

Name:	CTSK
Synonyms:	CTSO, CTSO2

Organism

Homo sapiens (Human)

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo

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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.

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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 osteclasts (bones).
Involvement in disease	Defects in CTSK are the cause of pycnodysostosis (PKND) [MIM:265800]. PKND is an autosomal recessive osteochondrodysplasia characterized by osteosclerosis and short stature.
Sequence similarities	Belongs to the peptidase C1 family.

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Ontologies

Keywords
Cellular component	Lysosome
Disease	Disease mutation
Domain	Signal
Molecular function	Hydrolase Protease Thiol protease
PTM	Glycoprotein Zymogen
Technical term	3D-structure
Gene Ontology (GO)
Biological process	proteolysis Ref.2 Traceable author statement. Source: ProtInc
Cellular component	lysosome Inferred from electronic annotation. Source: UniProtKB-KW
Molecular function	cysteine-type endopeptidase activity Traceable author statement. Source: ProtInc protein binding Inferred from physical interaction. Source: IntAct
Complete GO annotation...

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Binary interactions

With	Entry	#Exp.	IntAct	Notes
srp-6	O01462	1	EBI-715344,EBI-1549936	From a different organism.

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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.

VAR_015738

Natural variant

146

1

G → R in PKND.

VAR_006725

Natural variant

277

1

A → V in PKND.

VAR_015739

Natural variant

309

1

L → P in PKND.

VAR_006726

Experimental info

Sequence conflict

46

1

R → P in AAA95998. Ref.3

Secondary structure

1

.

329

Helix Strand Turn

Details...

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Sequences

Sequence

Length

Mass (Da)

Tools

P43235-1 [UniParc].

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

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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: 7805878] [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: 7818555] [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: 8585423] [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: 7576232] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA]. Tissue: Spleen.
[5]	"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: 15489334] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. Tissue: Skin.
[6]	"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: 9033587] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (1.8 ANGSTROMS).
[7]	"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. Veber D.F. Proc. Natl. Acad. Sci. U.S.A. 94:14249-14254(1997) [PubMed: 9405598] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (2.2 ANGSTROMS).
[8]	"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: 9893980] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (2.8 ANGSTROMS) OF ZYMOGEN FORM.
[9]	"Crystal structure of wild-type human procathepsin K." Sivaraman J., Lalumiere M., Menard R., Cygler M. Protein Sci. 8:283-290(1999) [PubMed: 10048321] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (3.2 ANGSTROMS).
[10]	"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: 8703060] [Abstract] Cited for: VARIANT PKND ARG-146.
[11]	"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: 9529353] [Abstract] Cited for: VARIANT PKND VAL-277.
[12]	"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: 10491211] [Abstract] Cited for: VARIANT PKND GLU-79.
[13]	"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: 10878663] [Abstract] Cited for: VARIANTS PKND GLU-79 AND PRO-309.
+	Additional computationally mapped references.

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Web resources

GeneReviews

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Cross-references

Sequence databases

U13665 mRNA. Translation: AAA65233.1.
X82153 mRNA. Translation: CAA57649.1.
U20280 mRNA. Translation: AAA95998.1.
S79895 mRNA. Translation: AAB35521.1.
BC016058 mRNA. Translation: AAH16058.1.

PIR

JC2476.

RefSeq

NP_000387.1.

UniGene

Hs.632466

3D structure databases

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	[»]
7PCK	X-ray	3.20	A/B/C/D	16-329	[»]

ModBase

Search...

Protein-protein interaction databases

IntAct

P43235.

Protein family/group databases

MEROPS

C01.036.
I29.007.

Genome annotation databases

Ensembl

ENSG00000143387. Homo sapiens. [Contig view]

GeneID

1513.

KEGG

hsa:1513.

Organism-specific databases

H-InvDB

HIX0001036.

HGNC

HGNC:2536. CTSK.

MIM

265800. phenotype.
601105. gene.

Orphanet

763. Pycnodysostosis.

PharmGKB

PA27034.

GenAtlas

Search...

GeneCards

Search...

Phylogenomic databases

HOVERGEN

P43235.

Gene expression databases

ArrayExpress

P43235.

CleanEx

HS_CTSK.
HS_CTSO.

GermOnline

ENSG00000143387. Homo sapiens.

Family and domain databases

InterPro

IPR000169. Pept_cys_AS.
IPR013128. Peptidase_C1A.
IPR000668. Peptidase_C1A_C.
IPR015644. Peptidase_C1A_cathepsin-K.
IPR013201. Prot_inhib_I29.
[Graphical view]

PANTHER

PTHR12411:SF55. CathpsnK_like. 1 hit.
PTHR12411. Peptidase_C1A. 1 hit.

Pfam

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

PRINTS

Names and origin

Protein attributes

General annotation (Comments)

Ontologies

Keywords

Gene Ontology (GO)

Binary interactions

With

Entry

#Exp.

IntAct

Notes

Sequence annotation (Features)

Molecule processing

Sites

Amino acid modifications

Natural variations

Experimental info

Secondary structure

Sequences

References

Web resources

Cross-references

Sequence databases

3D structure databases

Protein-protein interaction databases

Protein family/group databases

Genome annotation databases

Organism-specific databases

Phylogenomic databases

Gene expression databases

Family and domain databases