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FLASH GENE
Symbol CTSL contributors: mct - updated : 11-05-2016
HGNC name cathepsin L
HGNC id 2537
Location 9q21.33      Physical location : -
Synonym name
  • major excreted protein
  • cathepsin L
  • Synonym symbol(s) MEP, CATL, CTSL1, FLJ31037
    EC.number 3.4.22.15
    DNA
    TYPE functioning gene
    STRUCTURE 5.95 kb     8 Exon(s)
    10 Kb 5' upstream gene genomic sequence study
    regulatory sequence Promoter (CAAT box)
    cytosine-phosphate-guanine/HTF
    Binding site   transcription factor
    text structure
  • 29 putative transcription factor binding sites (GATA-1, AP-4, LMO2 and NF-Y, Sp1, Sp3, essential for transcription of the gene)
  • FOXO1-binding sites in promoter (Yamazaki 2010)
  • regulatory sequences in the 3prime region downstream of the cathepsin L gene and in the 3prime- and 5prime-flanking regions of GC/CCAAT sites of its promoter
  • MAPPING cloned Y linked N status confirmed
    Physical map
    LOC389766 9 similar to RIKEN cDNA 4921517D22 HBLD2 9q22.1 HESB like domain containing 2 ZCCHC6 9q21 zinc finger, CCHC domain containing 6 LOC392358 9 similar to 40S ribosomal protein S6 (Phosphoprotein NP33) GAS1 9q21.3-q22.1 growth arrest-specific 1 LOC157956 9q22.1 cell division cycle 20 pseudogene LOC392359 9 similar to transactivator HSM-1 DAPK1 9q34.1 death-associated protein kinase 1 CTSL 9q21-q22 cathepsin L LOC392360 9 similar to Eukaryotic translation initiation factor 3 subunit 1 (eIF-3 alpha) (eIF3 p35) (eIF3j) LOC392361 9 similar to Cathepsin L precursor (Major excreted protein) (MEP) LOC392362 9 similar to fructose-1,6-bisphosphatase 2; fructose-1,6-bisphosphatase isozyme 2; D-fructose-1,6-bisphosphate 1-phosphohydrolase; FBPase; muscle fructose-bisphosphatase; hexosediphosphatase LOC392363 9 similar to Cathepsin L precursor (Major excreted protein) (MEP) LOC392364 9 similar to chromosome 15 open reading frame 2 FLJ35866 LOC286235 9q22.2 hypothetical protein LOC286235 CCRK 9q22.2 cell cycle related kinase LOC158104 9q22.2 similar to 40S ribosomal protein S10 LOC389767 9 LOC389767 DKFZP434M131 9q22.1 DKFZP434M131 protein LOC389768 9 similar to potassium channel tetramerisation domain containing 1; chromosome 18 open reading frame 5 LOC389769 9 similar to Laminin receptor 1 SPIN 9q22.1-q22.3 spindlin LOC158046 9q22.2 similar to hypothetical protein BC014127 EDG3 9q22.1-q22.2 endothelial differentiation, sphingolipid G-protein-coupled receptor, 3 SHC3 9q22.1 src homology 2 domain containing transforming protein C3
    RNA
    TRANSCRIPTS type messenger
    identificationnb exonstypebpproduct
    ProteinkDaAAspecific expressionYearPubmed
    8 splicing 1587 - 333 most abundant in cancer cell lines 2013 24108784
  • is translated with highest efficiency and plays a key role in the over-expression of cathepsin L in cancer
  • overexpression during breast tumour progression
  • 8 splicing 1730 - 333 - 2013 24108784
    - splicing 1542 - - - 2002 12137950
    also called CTSL A2
    - splicing 1605 - - - 2002 12137950
    also called CTSL A1
    - - 262 - 39 - 2009 19291794
  • also called CATL AIII
  • most abundant in cell lines and is translated with highest efficiency
  • predominance of this most efficiently translated splice variant in malignant cells suggests that it plays a key role in the over-expression of cathepsin L in cancer
  • nuclear isoform that may play an important prognostic role in colorectal disease progression and patient outcome
  • 8 - 1625 - 333 - 2013 24108784
    8 - 1567 - 333 - 2013 24108784
    6 - 1141 - 151 - 2013 24108784
    EXPRESSION
    Type ubiquitous
       expressed in (based on citations)
    organ(s)
    SystemOrgan level 1Organ level 2Organ level 3Organ level 4LevelPubmedSpeciesStageRna symbol
    Cardiovascularheart   highly Homo sapiens
    Endocrineadrenal glandmedulla  highly Homo sapiens
     thyroid   highly
    Skin/Tegumentskin     Homo sapiens
    Urinarykidney    
    tissue
    SystemTissueTissue level 1Tissue level 2LevelPubmedSpeciesStageRna symbol
    Connectiveadipose  highly
    Connectivebone  highly
    Muscularstriatumskeletal  
    cells
    SystemCellPubmedSpeciesStageRna symbol
    Lymphoid/Immunemacrophage
    Nervousneuron
    NervousPurkinje cell
    not specificmast cell Homo sapiens
    cell lineage
    cell lines
    fluid/secretion
    at STAGE
    physiological period perinatal, pregnancy
    Text placenta, liver
    PROTEIN
    PHYSICAL PROPERTIES
    STRUCTURE
    motifs/domains
  • a heavy and a light chain linked by disulfide bounds
  • mono polymer dimer
    isoforms Precursor
    HOMOLOGY
    interspecies homolog to murine Ctsl
    Homologene
    FAMILY
  • papain family cysteine protease
  • peptidase C1 family
  • CATEGORY enzyme
    SUBCELLULAR LOCALIZATION extracellular
        intracellular
    intracellular,cytoplasm,organelle,lumen
    intracellular,cytoplasm,organelle,lysosome
    intracellular,cytoplasm,cytosolic,granule
    intracellular,cytoplasm,cytosolic,vesicle
    intracellular,nucleus
    text
  • secretory vesicles form or lysosomal form
  • CTSL and CTSB colocalize to the secretory granule compartment of skin mast cells
  • basic FUNCTION
  • cysteine proteinase cleaving collagen and elastin
  • involved in matrix degradation during endochondral ossification
  • having a critical role in the integration of circulating endothelial progenitor cells into ischemic tissue and is required for endothelial progenitor cells -mediated neovascularization
  • playing a potent role in degrading collagen, laminin, and implicated in tumor invasion and metastasis
  • playing a major role in intracellular protein catabolism
  • functioning as a prohormone -processing enzyme for production of the enkephalin peptide neurotransmitter(through secretory vesicules)
  • playing a role in peptide generation for MHC class 2 presentation
  • functions as a proneuropeptide processing enzyme for the conversion of proenkephalin to mature (Met)enkephalin, an opioid peptide neurotransmitter and hormone, as a distinct cysteine protease pathway for producing the enkephalin member of neuropeptides
  • playing an intracellular role in normal intestinal epithelial polarization and initiation of neoplasia
  • role in the degradation of the matrix protein fibronectin, insulin receptor (IR) and insulin-like growth factor-1 receptor (IGF1R), essential molecules for adipogenesis and glucose metabolism
  • may play important roles during normal placentation and in the etiology of pre-eclampsia
  • stabilizes epigenetic heterochromatin markers on pericentromeric heterochromatin and the Y chromosome through a novel mechanism that does not involve DNA methylation or affect heterochromatin structure and operates on both somatic and sex chromosomes
  • participates as a key proteolytic enzyme for NPY production in secretory vesicles
  • biological role in the production of NPY, a peptide neurotransmitter, and neuroendocrine hormone
  • responsible for processing and activation of proheparanase through multiple cleavages of a linker segment
  • important lysosomal proteinase involved in a variety of cellular functions including intracellular protein turnover, epidermal homeostasis, and hair development
  • improves cardiac function and inhibits cardiac hypertrophy, inflammation, and fibrosis through blocking AKT/GSK3B signaling
  • lysosomal proteinase whose expression is also up-regulated in the skeletal muscle during starvation
  • with CTSL, and CTSK, implicated in atherogenesis
  • CTSL1 and CTSB are central to the processing of protryptase(s) in human mast cells
  • CTSL, CTSZ, account for the lysosome's capacity to digest polyQ sequences, and are important in defending against the accumulation and toxicity of polyQ proteins
  • within lysosomes, CTSL is a major, probably the only, rate-limiting protease in the digestion of polyQ repeats in proteins, although many other lysosomal proteases can degrade the typical polypeptide sequences in myoglobin
  • CTSB, CTSK, CTSL1, CTSS may be putative leptin activity regulators in white adipose tissue (WAT)
  • negatively regulates bone marrow (BM) B-cell production and output therefore influencing the homeostasis of peripheral B cells
  • lysosomal CTSL attenuates cardiac hypertrophy and preserves cardiac function through facilitation of autophagy and proteasomal protein processing
  • cysteine protease that degrades the peri-tumoral tissue
  • CTSB and CTSL are essential in SNCA lysosomal degradation, establishing groundwork to explore mechanisms to enhance their cellular activity and levels as a potential strategy for clearance of SNCA
  • CELLULAR PROCESS protein, degradation
    PHYSIOLOGICAL PROCESS development
    PATHWAY
    metabolism
    signaling
    a component
    INTERACTION
    DNA
    RNA
    small molecule
    protein
  • inactivating alpa-1-protease inhibitor
  • direct target of FOXO1 in the skeletal muscle,
  • thereby suggesting a role for the FOXO1/cathepsin L pathway
    in fasting-induced skeletal muscle metabolic change and atrophy
  • down- or up-regulation of RAB4A expression or RAB4A function triggered inhibition or increase of CTSL secretion respectively
  • role for CTSL1 in the degradation of TP53BP1
  • it is likely that CTSL carries out initial cleavages yielding shorter peptides that are hydrolyzed to amino acids by CTSZ
  • BRCA1 loss activates (CTSL1)-mediated degradation of TP53BP1
  • cell & other
    REGULATION
    ASSOCIATED DISORDERS
    corresponding disease(s)
    Other morbid association(s)
    TypeGene ModificationChromosome rearrangementProtein expressionProtein Function
    tumoral     --over  
    in melanoma cell with metastatic potential
    constitutional     --low  
    in muscle of type 2 diabetes
    constitutional     --over  
    in obese and diabetic patients
    constitutional     --over  
    in a subpopulation of invasive cytotrophoblasts
    tumoral     --over  
    in breast tumor progression, due to stress-resistant mRNA translation and is a promoter of lung metastasis
    tumoral       gain of function
    by hypoxia in melanoma cells, which promotes tumour progression
    constitutional     --over  
    in fibroblasts leads to decreased TP53BP1 protein levels and changes in its cellular distribution, resulting in defective repair of DNA double-strand breaks (DSBs)
    Susceptibility
    Variant & Polymorphism
    Candidate gene
    Marker
  • CTSL levels in plasma of pancreatic cancer patients may be used as a potential prognostic marker for the disease: in plasma samples of pancreatic cancer patients was 5.98 2.5 ng/mL that was significantly higher compared to the levels in healthy controls (3.83 0.45) or chronic pancreatitis patients (3.97 1.06)
  • Therapy target
    SystemTypeDisorderPubmed
    diabete  
    target for the metabolic disorders
    cancer  
    may be utilized as a new target for enhancing the efficacy of chemotherapeutics against epithelial cancer
    ANIMAL & CELL MODELS
  • Deficiency of CTSL in mice results in a progressive dilated cardiomyopathy
  • mice deficient in cathepsin L have reduced adipose tissue mass