Cathepsin L1

Function

Cathepsin L1 is a member of the Peptidase C1 (cathepsin) MEROPS family, which plays an important role in diverse processes including normal lysosome mediated protein turnover, antigen and proprotein processing, and apoptosis. Its substrates include collagen and elastin, as well as alpha-1 protease inhibitor, a major controlling element of neutrophil elastase activity. The encoded protein has been implicated in several pathologic processes, including myofibril necrosis in myopathies and in myocardial ischemia, and in the renal tubular response to proteinuria. This protein, which is a member of the peptidase C1 family, is a dimer composed of disulfide-linked heavy and light chains, both produced from a single protein precursor. At least two transcript variants encoding the same protein have been found for this gene.

Viral entry

Cleavage of the SARS-CoV-2 S2 spike protein required for viral entry into cells can be accomplished by proteases TMPRSS2 located on the cell membrane, or by cathepsins (primarily cathepsin L) in endolysosomes. Hydroxychloroquine inhibits the action of cathepsin L in endolysosomes, but because cathepsin L cleavage is minor compared to TMPRSS2 cleavage, hydroxychloroquine does little to inhibit SARS-CoV-2 infection.

Inflammation

Although Cathepsin L is usually characterized as a lysosomal protease, it can be secreted, resulting in pathological inflammation. Cathepsin L and other cysteine cathepsins tend to be secreted by macrophages and other tissue-invading immune cells when causing pathological inflammation.

Interactions

CTSL1 has been shown to interact with Cystatin A.

Distribution

Cathepsin L has been reported in many organisms including fish, birds, mammals, and sponges.

References

References

1. (Feb 1993). "Cloning, genomic organization, and chromosomal localization of human cathepsin L". J Biol Chem.
2. (Jun 1988). "Complete nucleotide and deduced amino acid sequences of human and murine preprocathepsin L. An abundant transcript induced by transformation of fibroblasts". J Clin Invest.
3. "Entrez Gene: CTSL1 cathepsin L1".
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5. (1988). "Lysosomal cysteine proteinases". ISI Atlas of Science. Biochemistry.
6. (May 1988). "Complete nucleotide and deduced amino acid sequences of human and murine preprocathepsin L. An abundant transcript induced by transformation of fibroblasts". The Journal of Clinical Investigation.
7. (February 1988). "Active center differences between cathepsins L and B: the S1 binding region". FEBS Letters.
8. (2002). "Cysteine Peptidases of Mammals: Their Biological Roles and Potential Effects in the Oral Cavity and Other Tissues in Health and Disease". Critical Reviews in Oral Biology and Medicine.
9. (January 2022). "Mechanisms of SARS-CoV-2 entry into cells". Nature Reviews. Molecular Cell Biology.
10. (2022). "Cathepsin L in COVID-19: From Pharmacological Evidences to Genetics". Frontiers in Cellular and Infection Microbiology.
11. (October 2021). "Cathepsin L, transmembrane peptidase/serine subfamily member 2/4, and other host proteases in COVID-19 pathogenesis - with impact on gastrointestinal tract". World Journal of Gastroenterology.
12. Majerle, Andreja. (Sep 2003). "Protein inhibitors form complexes with procathepsin L and augment cleavage of the propeptide". Arch. Biochem. Biophys..
13. Estrada, S. (May 1998). "The role of Gly-4 of human cystatin A (stefin A) in the binding of target proteinases. Characterization by kinetic and equilibrium methods of the interactions of cystatin A Gly-4 mutants with papain, cathepsin B, and cathepsin L". Biochemistry.
14. (2014). "A murrel cysteine protease, cathepsin L: bioinformatics characterization, gene expression and proteolytic activity". Biologia.
15. (July 2006). "Human cathepsin L rescues the neurodegeneration and lethality in cathepsin B/L double-deficient mice". Biological Chemistry.