Cathepsin L1

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(Redirected from CTSL1)
Protein CTSL1 PDB 1cjl.png
Available structures
PDBHuman UniProt search: PDBe RCSB
AliasesCTSL, CATL, CTSL1, MEP, cathepsin L
External IDsOMIM: 116880 HomoloGene: 129366 GeneCards: CTSL
RefSeq (mRNA)


RefSeq (protein)


Location (UCSC)Chr 9: 87.72 – 87.73 Mbn/a
PubMed search[2]n/a
View/Edit Human

Cathepsin L1 is a protein that in humans is encoded by the CTSL1 gene.[3][4][5] The protein is a cysteine cathepsin, a lysosomal cysteine protease that plays a major role in intracellular protein catabolism.[6][7][8][9]


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.[10] 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.[5]

Viral entry[edit]

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.[11] 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.[11]


Although Cathepsin L is usually characterized as a lysosomal protease, it can be secreted, resulting in pathological inflammation.[12] Cathepsin L and other cysteine cathepsins tend to be secreted by macrophages and other tissue-invading immune cells when causing pathological inflammation.[13]


CTSL1 has been shown to interact with Cystatin A.[14][15]


Cathepsin L has been reported in many organisms including fish,[16] birds, mammals, and sponges.[17]

See also[edit]


  1. ^ a b c GRCh38: Ensembl release 89: ENSG00000135047 - Ensembl, May 2017
  2. ^ "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  3. ^ Chauhan SS, Popescu NC, Ray D, Fleischmann R, Gottesman MM, Troen BR (Feb 1993). "Cloning, genomic organization, and chromosomal localization of human cathepsin L". J Biol Chem. 268 (2): 1039–45. doi:10.1016/S0021-9258(18)54038-2. PMID 8419312.
  4. ^ Joseph LJ, Chang LC, Stamenkovich D, Sukhatme VP (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. 81 (5): 1621–9. doi:10.1172/JCI113497. PMC 442598. PMID 2835398.
  5. ^ a b "Entrez Gene: CTSL1 cathepsin L1".
  6. ^ Barrett AJ, Kirschke H (1981). "Cathepsin B, Cathepsin H, and cathepsin L". Methods in Enzymology. 80 Pt C: 535–561. doi:10.1016/s0076-6879(81)80043-2. PMID 7043200.
  7. ^ Barrett AJ, Buttle DJ, Mason RW (1988). "Lysosomal cysteine proteinases". ISI Atlas of Science. Biochemistry. 1: 256–260.
  8. ^ Joseph LJ, Chang LC, Stamenkovich D, Sukhatme VP (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. 81 (5): 1621–1629. doi:10.1172/JCI113497. PMC 442598. PMID 2835398.
  9. ^ Kirschke H, Wikstrom P, Shaw E (February 1988). "Active center differences between cathepsins L and B: the S1 binding region". FEBS Letters. 228 (1): 128–130. doi:10.1016/0014-5793(88)80600-8. PMID 3342870.
  10. ^ Dickinson DP (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. 13 (3): 238–75. doi:10.1177/154411130201300304. PMID 12090464.
  11. ^ a b Jackson CB, Farzan M, Chen B, Choe H (January 2022). "Mechanisms of SARS-CoV-2 entry into cells". Nature Reviews. Molecular Cell Biology. 23 (1): 3–20. doi:10.1038/s41580-021-00418-x. PMC 8491763. PMID 34611326.
  12. ^ Gomes CP, Fernandes DE, Casimiro F, da Mata GF, Passos MT, Varela P, et al. (2022). "Cathepsin L in COVID-19: From Pharmacological Evidences to Genetics". Frontiers in Cellular and Infection Microbiology. 10: 589505. doi:10.3389/fcimb.2020.589505. PMC 7753008. PMID 33364201.
  13. ^ Berdowska I, Matusiewicz M (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. 27 (39): 6590–6600. doi:10.3748/wjg.v27.i39.6590. PMC 8554394. PMID 34754154.
  14. ^ Majerle, Andreja; Jerala Roman (Sep 2003). "Protein inhibitors form complexes with procathepsin L and augment cleavage of the propeptide". Arch. Biochem. Biophys. 417 (1): 53–8. doi:10.1016/S0003-9861(03)00319-9. ISSN 0003-9861. PMID 12921779.
  15. ^ Estrada, S; Nycander M; Hill N J; Craven C J; Waltho J P; Björk I (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. 37 (20): 7551–60. doi:10.1021/bi980026r. ISSN 0006-2960. PMID 9585570.
  16. ^ Venkatesh K, Prasanth B, Rajesh P, Annie JG, Mukesh P, Jesu A (2014). "A murrel cysteine protease, cathepsin L: bioinformatics characterization, gene expression and proteolytic activity". Biologia. 39 (3): 395–406. doi:10.2478/s11756-013-0326-8.
  17. ^ Sevenich L, Pennacchio LA, Peters C, Reinheckel T (July 2006). "Human cathepsin L rescues the neurodegeneration and lethality in cathepsin B/L double-deficient mice". Biological Chemistry. 387 (7): 885–91. doi:10.1515/BC.2006.112. PMID 16913838. S2CID 27739485.

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