cathepsin L1

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.{{cite journal | vauthors = Dickinson DP | title = Cysteine Peptidases of Mammals: Their Biological Roles and Potential Effects in the Oral Cavity and Other Tissues in Health and Disease | journal = Critical Reviews in Oral Biology and Medicine | volume = 13 | issue = 3 | pages = 238–75 | date = 2002 | pmid = 12090464 | doi = 10.1177/154411130201300304 }} 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.

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.{{cite journal | vauthors = Jackson CB, Farzan M, Chen B, Choe H | title = Mechanisms of SARS-CoV-2 entry into cells | journal = Nature Reviews. Molecular Cell Biology | volume = 23 | issue = 1 | pages = 3–20 | date = January 2022 | pmid = 34611326 | pmc = 8491763 | doi = 10.1038/s41580-021-00418-x }} 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.

Although Cathepsin L is usually characterized as a lysosomal protease, it can be secreted, resulting in pathological inflammation.{{cite journal | vauthors = Gomes CP, Fernandes DE, Casimiro F, da Mata GF, Passos MT, Varela P, Mastroianni-Kirsztajn G, Pesquero JB | display-authors = 6 | title = Cathepsin L in COVID-19: From Pharmacological Evidences to Genetics | journal = Frontiers in Cellular and Infection Microbiology | volume = 10 | pages = 589505 | date = 2022 | pmid = 33364201 | pmc = 7753008 | doi = 10.3389/fcimb.2020.589505 | doi-access = free }} Cathepsin L and other cysteine cathepsins tend to be secreted by macrophages and other tissue-invading immune cells when causing pathological inflammation.{{cite journal | vauthors = Berdowska I, Matusiewicz M | title = Cathepsin L, transmembrane peptidase/serine subfamily member 2/4, and other host proteases in COVID-19 pathogenesis - with impact on gastrointestinal tract | journal = World Journal of Gastroenterology | volume = 27 | issue = 39 | pages = 6590–6600 | date = October 2021 | pmid = 34754154 | pmc = 8554394 | doi = 10.3748/wjg.v27.i39.6590 | doi-access = free }}

CTSL1 has been shown to interact with Cystatin A.{{cite journal |doi=10.1016/S0003-9861(03)00319-9 |last=Majerle |first=Andreja |author2=Jerala Roman |date=Sep 2003 |title=Protein inhibitors form complexes with procathepsin L and augment cleavage of the propeptide |journal=Arch. Biochem. Biophys. |volume=417 |issue=1 |pages=53–8 | issn = 0003-9861| pmid = 12921779 }}{{cite journal |last=Estrada |first=S |author2=Nycander M|author3=Hill N J|author4=Craven C J|author5=Waltho J P|author6=Björk I |date=May 1998 |title=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 |journal=Biochemistry |volume=37 |issue=20 |pages=7551–60 | issn = 0006-2960| pmid = 9585570 |doi = 10.1021/bi980026r }}

Cathepsin L has been reported in many organisms including fish,{{cite journal | title = A murrel cysteine protease, cathepsin L: bioinformatics characterization, gene expression and proteolytic activity |vauthors = Venkatesh K, Prasanth B, Rajesh P, Annie JG, Mukesh P, Jesu A |journal = Biologia |year = 2014 |volume = 39 |issue = 3 |pages = 395–406 |doi=10.2478/s11756-013-0326-8|doi-access = free |bibcode = 2014Biolg..69..395K }} birds, mammals, and sponges.{{cite journal | vauthors = Sevenich L, Pennacchio LA, Peters C, Reinheckel T | title = Human cathepsin L rescues the neurodegeneration and lethality in cathepsin B/L double-deficient mice | journal = Biological Chemistry | volume = 387 | issue = 7 | pages = 885–91 | date = July 2006 | pmid = 16913838 | doi = 10.1515/BC.2006.112 | s2cid = 27739485 | url = https://digital.library.unt.edu/ark:/67531/metadc896009/ }}

• Cathepsin L2 (also known as cathepsin V)

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• The MEROPS online database for peptidases and their inhibitors: [https://archive.today/20121223060820/http://merops.sanger.ac.uk/cgi-bin/merops.cgi?id=C01.032 C01.032]
• {{MeshName|Cathepsin+L}}

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{{Cysteine proteases}}

{{Enzymes}}

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Category:Cathepsins

Category:EC 3.4.22

Category:Extracellular matrix remodeling enzymes

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