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FLASH GENE
Symbol CTSK contributors: mct/pgu - updated : 06-10-2015
HGNC name cathepsin K
HGNC id 2536
Corresponding disease
PYCD pycnodysostosis
Location 1q21.3      Physical location : 150.768.686 - 150.780.812
Synonym name
  • cathepsin O1
  • cathepsin K (pycnodysostosis)
  • cathepsin O2
  • cathepsin X
  • Synonym symbol(s) CTSO, CTSO1, CTSO2, PKND, CATK, CTS02, PYCD, MGC23107
    EC.number 3.4.22.38
    DNA
    TYPE functioning gene
    STRUCTURE 12.13 kb     8 Exon(s)
    Genomic sequence alignment details
    10 Kb 5' upstream gene genomic sequence study
    regulatory sequence Promoter
    Binding site   transcription factor
    text structure
  • two AP-1sites
  • two consensus Sp1 binding sites and a rich GtC region are identified in the promoter region as potential regulatory elements
  • three NFATC1 binding sites upstream the transcriptional start site
  • MAPPING cloned Y linked Y status confirmed
    Map cen - D1S442 - D1S2344 - CTSK /CTSS - MCL1 - D1S498 - D1S2347 - D1S2343 /D1S2345 - qter
    Authors (PMID: 8703060)
    RNA
    TRANSCRIPTS type messenger
    identificationnb exonstypebpproduct
    ProteinkDaAAspecific expressionYearPubmed
    8 - 1702 - 329 - 2009 19338743
    EXPRESSION
    Type widely
       expressed in (based on citations)
    organ(s)
    SystemOrgan level 1Organ level 2Organ level 3Organ level 4LevelPubmedSpeciesStageRna symbol
    Respiratorylung     Homo sapiens
    Skin/Tegumentskin     Homo sapiens
    tissue
    SystemTissueTissue level 1Tissue level 2LevelPubmedSpeciesStageRna symbol
    Connectiveadipose  highly
    Connectivebone  highly
    Epithelialbarrier liningepidermis   Homo sapiens
    cells
    SystemCellPubmedSpeciesStageRna symbol
    Skeletonosteoclast Homo sapiens
    Skin/Tegument  Homo sapiens
    cell lineage
    cell lines
    fluid/secretion
    at STAGE
    PROTEIN
    PHYSICAL PROPERTIES
    STRUCTURE
    motifs/domains
  • two potential N-glycosylation sites
  • cathepsin propeptide inhibitor domain
  • peptidase C1 domain
  • a catalytic site consists of two domains folded together to give a V-shaped active site cleft configuration
  • conjugated GlycoP
    isoforms Precursor a 15AA N terminal and a 99-residue propreptide
    HOMOLOGY
    intraspecies homolog to CSTL,CSTS
    Homologene
    FAMILY
  • papain cysteine protease family
  • peptidase C1 family
  • CATEGORY enzyme
    SUBCELLULAR LOCALIZATION     intracellular
    intracellular,cytoplasm,organelle,lysosome
    text synthesizing and secreting cathepsin K into the extracellular compartment at the attachment site between osteoclasts and the bone surface, where in the organic matrix is subsequently degraded by cathepsin K
    basic FUNCTION
  • playing an important role in the homeostasis of the dermal extracellular matrix and the dynamic equilibrium between matrix synthesis and proteolytic degradation
  • P cysteine proteinase, exhibiting strong degradative activity against the extracellular matrix and involved in osteoclast-mediated bone destruction
  • likely major lysosomal protein in bone matrix resorption
  • critical protease in synovial fibroblast-mediated collagen degradation
  • having dual functions as a cysteine protease and a regulator of osteoclasts survival, playing a role as a potential regulator of osteoclasts apoptosis and senescence
  • may mediate osteoclasts apoptosis and senescence through the Tp53-dependent pathway
  • lysosomal cysteine protease with strong collagenolytic activity that mediates bone resorption in osteoclasts
  • may play a role in maintaining homeostasis of the extracellular matrix outside of bone
  • may play an important role in melanoma invasion and metastasis by mediating intracellular degradation of matrix proteins after phagocytosis
  • responsible for the degradation of type I collagen in osteoclast-mediated bone resorption
  • playing a role in bone resorption demonstrating its ability to regulate the initiation and termination of the resorption process in an autocrine manner
  • with CTSL, and CTSK, implicated in atherogenesis
  • collagenase activity of cathepsin K requires a highly specific interaction with chondroitin 4-Sulfate (C4-s)
  • late differentiation marker during osteoclastogenesis
  • plays an essential role in abdominal aortic aneurysm (AAA) formation by promoting T-cell proliferation, vascular SMC apoptosis, and elastin degradation and by affecting vascular cell protease expression and activities
  • cysteine peptidase cathepsin K that is a major player in extracellular proteolysis
  • CTSB, CTSK, CTSL1, CTSS may be putative leptin activity regulators in white adipose tissue (WAT)
  • cathepsin K ablation mitigates pressure overload-induced hypertrophy, possibly via inhibition of the mammalian target of rapamycin and ERK pathways
  • major lysosomal collagenase produced by osteoclasts, playing an important role in bone resorption
  • major collagenolytic protease in bone that facilitates physiological as well as pathological bone degradation
  • is organized into elongated C-shaped protease dimers that reveal a putative collagen-binding interface aided by glycosaminoglycans
  • CELLULAR PROCESS
    PHYSIOLOGICAL PROCESS
    PATHWAY
    metabolism
    signaling
    a component
    INTERACTION
    DNA
    RNA
    small molecule
    protein
  • interaction with type I collagen is required for the release of cryptic Arg-Gly-Asp motifs during the initial attachment of osteoclasts and termination of resorption via the creation of autocrine signals originating from type I collagen degradation
  • both cathepsins K and S cleave elastin, albeit with different affinities and catalytic rates, but only cathepsin K cleaves triple helical type I and II collagens
  • multifunctional extracellular chaperone clusterin is a cathepsin K-binding protein
  • cathepsin S binds to cathepsin K in a catalytically productive manner to form an enzyme-enzyme complex
  • cathepsin cannibalism is a phenomenon, where cathepsin S degrades cathepsin K and, in the presence of ECM substrate proteins, can result in a reduction of total substrate proteolysis
  • cathepsin K exocytosis is controlled by PRKCD through modulation of the actin bundling protein myristoylated alanine-rich C-kinase substrate (MARCKS)
  • specific binding of CTSK at the edge of the fibrillar gap region of collagen fibers, which suggest initial cleavage events at the N- and C-terminal ends of tropocollagen molecules 3)
  • CTSK was responsible for the activation of pro-MMP9, with a key link between CTSK expression in tumors and bone and ECM remodeling, through MMP9 activation
  • cell & other
    REGULATION
    induced by NFATC1 binding in the promoter, after TNFSF11 activation via the Ca2+/calmodulin/calcineurin signaling pathway
    ASSOCIATED DISORDERS
    corresponding disease(s) PYCD
    Other morbid association(s)
    TypeGene ModificationChromosome rearrangementProtein expressionProtein Function
    tumoral     --over  
    in osteoclastoma
    tumoral     --over  
    in metastases of prostate cancer
    constitutional     --over  
    CTSK levels were increased in the serum of tuberculosis patients compared to controls
    constitutional     --over  
    were markedly elevated in human hearts of end-stage dilated cardiomyopathy
    constitutional   deletion    
    in osteoclasts enhances bone formation by increasing the generation of osteoclast-derived sphingosine-1-phosphate (S1P)
    constitutional     --over  
    in human abdominal aortic aneurysm (AAA) lesions
    Susceptibility
    Variant & Polymorphism
    Candidate gene
    Marker
    Therapy target
    SystemTypeDisorderPubmed
    osteoarticularboneostéoporosis
    decreasing the activity of cathepsin K by specific inhibitors or antisense approaches could provide a beneficial treatment for pathologic processes (arthritis and osteoporosis)
    osteoarticularboneostéoporosis
    Cathepsin K inhibitors prevent matrix-derived growth factor degradation by human osteoclasts and similarly augmented bone morphogenetic protein BMP2 release
    cancerskin 
    clinical use of CTSK inhibitors, a class of medication currently in clinical trials for the treatment of osteoporosis, may be a promising avenue for the treatment of melanoma
    immunologyautoimmunearticular
    CTSK may be targeted to treat rheumatoid arthritis and periodontitis simultaneously due to its shared osteoimmune role
    ANIMAL & CELL MODELS
  • osteopetrosis in cathepsin K deficient in mice
  • mice deficient in cathepsin K have reduced adipose tissue mass
  • AAA lesions from Ctsk-deficient mice showed reduced elastinolytic cathepsin activities compared with those from wild-type control mice
  • global deletion of Ctsk in mice decreases bone resorption, leading to osteopetrosis, but also increases the bone formation rate (BFR)
  • gene deletion of Ctsk in mice accelerated callus size resolution, significantly increased callus mineralized mass, and improved mechanical strength as compared to wild type mice