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FLASH GENE
Symbol CTSS contributors: mct - updated : 06-10-2015
HGNC name cathepsin S
HGNC id 2545
Location 1q21.3      Physical location : 150.702.553 - 150.738.305
Synonym symbol(s) MGC3886
EC.number 3.4.22.27
DNA
TYPE functioning gene
STRUCTURE 35.75 kb     8 Exon(s)
Genomic sequence alignment details
10 Kb 5' upstream gene genomic sequence study
regulatory sequence Binding site
text structure CA repeat binding AP-1
MAPPING cloned Y linked   status provisional
RNA
TRANSCRIPTS type messenger
identificationnb exonstypebpproduct
ProteinkDaAAspecific expressionYearPubmed
8 - 4100 - 331 - 1992 1377692
- - 3957 - 281 - 1992 1377692
EXPRESSION
Type ubiquitous
   expressed in (based on citations)
organ(s)
SystemOrgan level 1Organ level 2Organ level 3Organ level 4LevelPubmedSpeciesStageRna symbol
Cardiovascularheart    
Digestiveintestinesmall intestinejejunum highly
 pharynx   highly
Lymphoid/Immunelymph node    
 spleen   highly
Respiratoryrespiratory tracttrachea  highly
tissue
SystemTissueTissue level 1Tissue level 2LevelPubmedSpeciesStageRna symbol
Blood / Hematopoietic    
Connectiveadipose  highly
cells
SystemCellPubmedSpeciesStageRna symbol
Lymphoid/ImmuneB cell Homo sapiens
Lymphoid/Immunemacrophage
not specificchondrocyte Homo sapiens
Skin/Tegumentkeratinocyte Homo sapiens
cell lineage
cell lines
fluid/secretion
at STAGE
PROTEIN
PHYSICAL PROPERTIES
STRUCTURE
motifs/domains
mono polymer monomer
isoforms Precursor
HOMOLOGY
Homologene
FAMILY
  • peptidase C1 family
  • CATEGORY enzyme , immunity/defense , regulatory
    SUBCELLULAR LOCALIZATION extracellular
        intracellular
    intracellular,cytoplasm,organelle,lumen
    intracellular,cytoplasm,organelle,membrane
    intracellular,cytoplasm,organelle,endosome
    intracellular,cytoplasm,organelle,lysosome
    text
  • IFI30 and CTSS colocalized within lysosomes of B cells
  • basic FUNCTION
  • cysteine protease having a central role in remodeling the extracellular matrix and implicated in the etiology of cardiovascular disease
  • cysteine endoprotease specifically involved in MHCII-associated chain processing and peptide loading
  • lysosomal cysteine proteinase may be participating in the degradation of antigenic proteins to peptides for presentation on MHC class II molecules
  • playing a specific role in the generation of antigenic peptides
  • playing a functional role in angiogenesis and neoplastic progression
  • having a potential role to promote preadipocyte differentiation
  • may promote adipogenesis, at least in part, by degrading fibronectin in the early steps of differentiation, and having a possible contribution to fat mass expansion in obesity
  • may play a role in determining the Apo-A1 and HDL-C profiles and may thus influence reverse cholesterol transport
  • may play a role in the activation of an adoptive immune response
  • with CTSL, and CTSK, implicated in atherogenesis
  • importance of CTSB, CTSS and Cystatins in immunomodulation
  • in lysosomes is essential for mitophagy processing in macrophages
  • CTSB, CTSK, CTSL1, CTSS may be putative leptin activity regulators in white adipose tissue (WAT)
  • has a much lower binding affinity and catalytic rate for collagen I and cleaves only at the telopeptide regions of the molecule, regions that are increasingly exposed after hydrolysis by CTSK
  • may participate in basement membrane (BM) proteolysis, in addition to already identified proteases
  • physiologic mechanism that regulates CTSS and has implications for fine tuning MHC class II-restricted Ag processing and for the development of CTSS inhibitors, which are under investigation for the treatment of autoimmune disease
  • may contribute significantly to cartilage degradation and may thus be considered a potential drug target in joint diseases
  • CTSS secreted by microglia during the dark-phase decreases the spine density of the cortical neurons by modifying the perisynaptic environment, leading to downscaling of the synaptic strength during the subsequent light-phase
  • peripheral pivotal role of CTSS in the development of neuropathic pain through the antigen-specific activation of CD4(+) T-cells
  • tumor-promoting role of autophagy in tumor-associated macrophages (TAMs), suggesting CTSS could be a potential target for cancer therapy
  • cysteine protease that controls adipocyte differentiation and has been implicated in vascular and metabolic complications of obesity
  • CTSZ is the compensatory protease that regulates the acquired tumor-promoting functions of lesions deficient in both CTSB and CTSS
  • CELLULAR PROCESS
    PHYSIOLOGICAL PROCESS
    text vascular matrix remodeling
    PATHWAY
    metabolism
    signaling
    a component
    INTERACTION
    DNA
    RNA
    small molecule
    protein
  • elastin
  • 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
  • IFI30 expression posttranscriptionally decreased the steady-state protein expression of CTSS in primary B cells and B-cell lines
  • CTSS is a biased agonist of F2RL1 that causes F2RL1- and TRPV4-dependent inflammation and pain
  • LRP1-mediated cardiomyocyte intracellular cholesteryl ester (CE) accumulation alters the structural and physical characteristics of secreted tropoelastin (TE) through an increase in CTSS mature protein level
  • IFI30 is required for optimal activity of the lysosomal cysteine protease, CTSS
  • cell & other
    REGULATION
    ASSOCIATED DISORDERS
    corresponding disease(s)
    Other morbid association(s)
    TypeGene ModificationChromosome rearrangementProtein expressionProtein Function
    tumoral     --over  
    in lung tumor in progression
    constitutional     --over  
    in obese woman and reduced after gastric surgery-induced weight loss
    constitutional       loss of function
    cathepsin S deficiency alters the balance between adipocyte and osteoblast differentiation, increases bone turnover, and changes bone microarchitecture
    constitutional       gain of function
    in psoriatic keratinocytes
    Susceptibility
    Variant & Polymorphism
    Candidate gene a potential candidate gene in obesity
    Marker
  • CTSS activity in tears can be measured in a simple, quick, economical, and noninvasive manner and may serve as a novel biomarker for autoimmune dacryoadenitis during the diagnostic evaluation for Sjögren syndrom
  • Therapy target
    SystemTypeDisorderPubmed
    obesity  
    cathepsin S inhibitors are under clinical evaluation for diseases with impaired immune response, such as asthma and rheumatoid arthritis and could be tested in obese subjects, if cathepsin S inhibition proved to be of therapeutic relevance for obesity-lin
    cancerdigestiveliver
    CTSS silencing by lentivirus mediated RNAi provides an attractive anti-cancer strategy and a novel strategy for the treatment of human HCC
    cancer  
    therapeutic target in cancer
    ANIMAL & CELL MODELS