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HMDB Protein ID HMDBP13478
Secondary Accession Numbers None
Name Procathepsin L
  1. Cathepsin L1
  2. Major excreted protein
  3. MEP
Gene Name CTSL
Protein Type Unknown
Biological Properties
General Function Not Available
Specific Function Thiol protease important for the overall degradation of proteins in lysosomes (Probable). Plays a critical for normal cellular functions such as general protein turnover, antigen processing and bone remodeling. Involved in the solubilization of cross-linked TG/thyroglobulin and in the subsequent release of thyroid hormone thyroxine (T4) by limited proteolysis of TG/thyroglobulin in the thyroid follicle lumen (By similarity). In neuroendocrine chromaffin cells secretory vesicles, catalyzes the prohormone proenkephalin processing to the active enkephalin peptide neurotransmitter (By similarity). In thymus, regulates CD4(+) T cell positive selection by generating the major histocompatibility complex class II (MHCII) bound peptide ligands presented by cortical thymic epithelial cells. Also mediates invariant chain processing in cortical thymic epithelial cells (By similarity). Major elastin-degrading enzyme at neutral pH. Accumulates as a mature and active enzyme in the extracellular space of antigen presenting cells (APCs) to regulate degradation of the extracellular matrix in the course of inflammation (By similarity). Secreted form generates endostatin from COL18A1 (PubMed:10716919). Critical for cardiac morphology and function. Plays an important role in hair follicle morphogenesis and cycling, as well as epidermal differentiation (By similarity). Required for maximal stimulation of steroidogenesis by TIMP1 (By similarity).Functions in the regulation of cell cycle progression through proteolytic processing of the CUX1 transcription factor (PubMed:15099520). Translation initiation at downstream start sites allows the synthesis of isoforms that are devoid of a signal peptide and localize to the nucleus where they cleave the CUX1 transcription factor and modify its DNA binding properties (PubMed:15099520).(Microbial infection) Facilitates human coronaviruses SARS-CoV and SARS-CoV-2 infections via proteolysis of coronavirus spike (S) glycoproteins in lysosome for entry into host cell (PubMed:32142651, PubMed:32221306, PubMed:16339146, PubMed:18562523). Proteolysis within lysosomes is sufficient to activate membrane fusion by coronaviruses SARS-CoV and EMC (HCoV-EMC) S as well as Zaire ebolavirus glycoproteins (PubMed:16081529, PubMed:26953343, PubMed:18562523).
  • Antigen processing and presentation
  • Apoptosis
  • Autophagy - animal
  • Fluid shear stress and atherosclerosis
  • Lysosome
  • Phagosome
  • Proteoglycans in cancer
  • Rheumatoid arthritis
Reactions Not Available
GO Classification
Biological Process
viral entry into host cell
protein autoprocessing
viral entry into host cell via membrane fusion with the plasma membrane
elastin catabolic process
extracellular matrix disassembly
collagen catabolic process
immune response
adaptive immune response
toll-like receptor signaling pathway
antigen processing and presentation of exogenous peptide antigen via MHC class II
antigen processing and presentation of peptide antigen
CD4-positive, alpha-beta T cell lineage commitment
enkephalin processing
proteolysis involved in cellular protein catabolic process
zymogen activation
antigen processing and presentation
cellular response to thyroid hormone stimulus
fusion of virus membrane with host endosome membrane
macrophage apoptotic process
receptor-mediated endocytosis of virus by host cell
regulation of keratinocyte differentiation
Cellular Component
extracellular vesicular exosome
plasma membrane
Golgi apparatus
chromaffin granule
lysosomal lumen
multivesicular body
extracellular region
collagen-containing extracellular matrix
extracellular space
apical plasma membrane
intracellular membrane-bounded organelle
endocytic vesicle lumen
endolysosome lumen
Molecular Function
proteoglycan binding
collagen binding
cysteine-type endopeptidase activity
fibronectin binding
histone binding
cysteine-type peptidase activity
serpin family protein binding
Cellular Location Not Available
Gene Properties
Chromosome Location Not Available
Locus Not Available
SNPs Not Available
Gene Sequence Not Available
Protein Properties
Number of Residues 333
Molecular Weight 37563.97
Theoretical pI 5.452
Pfam Domain Function
  • 1-17;
Transmembrane Regions Not Available
Protein Sequence Not Available
GenBank ID Protein Not Available
UniProtKB/Swiss-Prot ID P07711
UniProtKB/Swiss-Prot Entry Name CATL1_HUMAN
GenBank Gene ID Not Available
GeneCard ID Not Available
GenAtlas ID Not Available
HGNC ID Not Available
General References
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  6. Zhang H, Li XJ, Martin DB, Aebersold R: Identification and quantification of N-linked glycoproteins using hydrazide chemistry, stable isotope labeling and mass spectrometry. Nat Biotechnol. 2003 Jun;21(6):660-6. Epub 2003 May 18. [PubMed:12754519 ]
  7. Gal S, Gottesman MM: Isolation and sequence of a cDNA for human pro-(cathepsin L). Biochem J. 1988 Jul 1;253(1):303-6. [PubMed:3421948 ]
  8. Joseph LJ, Chang LC, Stamenkovich D, Sukhatme VP: Complete nucleotide and deduced amino acid sequences of human and murine preprocathepsin L. An abundant transcript induced by transformation of fibroblasts. J Clin Invest. 1988 May;81(5):1621-9. [PubMed:2835398 ]
  9. Ritonja A, Popovic T, Kotnik M, Machleidt W, Turk V: Amino acid sequences of the human kidney cathepsins H and L. FEBS Lett. 1988 Feb 15;228(2):341-5. [PubMed:3342889 ]
  10. Joseph L, Lapid S, Sukhatme V: The major ras induced protein in NIH3T3 cells is cathepsin L. Nucleic Acids Res. 1987 Apr 10;15(7):3186. [PubMed:3550705 ]
  11. Mason RW, Walker JE, Northrop FD: The N-terminal amino acid sequences of the heavy and light chains of human cathepsin L. Relationship to a cDNA clone for a major cysteine proteinase from a mouse macrophage cell line. Biochem J. 1986 Dec 1;240(2):373-7. [PubMed:3545185 ]
  12. Coulombe R, Grochulski P, Sivaraman J, Menard R, Mort JS, Cygler M: Structure of human procathepsin L reveals the molecular basis of inhibition by the prosegment. EMBO J. 1996 Oct 15;15(20):5492-503. [PubMed:8896443 ]
  13. Fujishima A, Imai Y, Nomura T, Fujisawa Y, Yamamoto Y, Sugawara T: The crystal structure of human cathepsin L complexed with E-64. FEBS Lett. 1997 Apr 21;407(1):47-50. [PubMed:9141479 ]
  14. Burkard TR, Planyavsky M, Kaupe I, Breitwieser FP, Burckstummer T, Bennett KL, Superti-Furga G, Colinge J: Initial characterization of the human central proteome. BMC Syst Biol. 2011 Jan 26;5:17. doi: 10.1186/1752-0509-5-17. [PubMed:21269460 ]
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