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
Cleavage of the SARS-CoV-2S2spike protein required for viral entry into cells can be accomplished by proteasesTMPRSS2 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]
Inflammation
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]
^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. PMC442598. PMID 2835398.
^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.
^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.
^ abJackson 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. PMC8491763. PMID 34611326.
^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. PMC7753008. PMID 33364201.
^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. PMC8554394. PMID 34754154.
^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.
^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.
^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.
^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.
Further reading
Smith CG, Smith MT, Besch NF, et al. (1980). "Effect of delta 9-tetrahydrocannabinol (THC) on female reproductive function". Advances in the Biosciences. 22–23: 449–67. doi:10.1016/b978-0-08-023759-6.50040-8. ISBN9780080237596. PMID 116880.
Goretzki L, Schmitt M, Mann K, et al. (1992). "Effective activation of the proenzyme form of the urokinase-type plasminogen activator (pro-uPA) by the cysteine protease cathepsin L.". FEBS Lett. 297 (1–2): 112–8. doi:10.1016/0014-5793(92)80339-I. PMID 1551416. S2CID 45421148.
Dunn AD, Crutchfield HE, Dunn JT (1991). "Thyroglobulin processing by thyroidal proteases. Major sites of cleavage by cathepsins B, D, and L." J. Biol. Chem. 266 (30): 20198–204. doi:10.1016/S0021-9258(18)54909-7. PMID 1939080.
Stearns NA, Dong JM, Pan JX, et al. (1991). "Comparison of cathepsin L synthesized by normal and transformed cells at the gene, message, protein, and oligosaccharide levels". Arch. Biochem. Biophys. 283 (2): 447–57. doi:10.1016/0003-9861(90)90666-M. PMID 2275556.
Ritonja A, Popović T, Kotnik M, et al. (1988). "Amino acid sequences of the human kidney cathepsins H and L." FEBS Lett. 228 (2): 341–5. doi:10.1016/0014-5793(88)80028-0. PMID 3342889. S2CID 45768546.
Gal S, Gottesman MM (1988). "Isolation and sequence of a cDNA for human pro-(cathepsin L)". Biochem. J. 253 (1): 303–6. doi:10.1042/bj2530303. PMC1149292. PMID 3421948.
Johnson DA, Barrett AJ, Mason RW (1986). "Cathepsin L inactivates alpha 1-proteinase inhibitor by cleavage in the reactive site region". J. Biol. Chem. 261 (31): 14748–51. doi:10.1016/S0021-9258(18)66935-2. PMID 3490478.
Mason RW, Walker JE, Northrop FD (1987). "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. 240 (2): 373–7. doi:10.1042/bj2400373. PMC1147428. PMID 3545185.
Joseph L, Lapid S, Sukhatme V (1987). "The major ras induced protein in NIH3T3 cells is cathepsin L." Nucleic Acids Res. 15 (7): 3186. doi:10.1093/nar/15.7.3186. PMC340927. PMID 3550705.
Kärgel HJ, Dettmer R, Etzold G, et al. (1982). "Action of rat liver cathepsin L on glucagon". Acta Biol. Med. Ger. 40 (9): 1139–43. PMID 7340337.
Bevec T, Stoka V, Pungercic G, et al. (1996). "Major histocompatibility complex class II-associated p41 invariant chain fragment is a strong inhibitor of lysosomal cathepsin L." J. Exp. Med. 183 (4): 1331–8. doi:10.1084/jem.183.4.1331. PMC2192513. PMID 8666891.
Coulombe R, Grochulski P, Sivaraman J, et al. (1996). "Structure of human procathepsin L reveals the molecular basis of inhibition by the prosegment". EMBO J. 15 (20): 5492–503. doi:10.1002/j.1460-2075.1996.tb00934.x. PMC452294. PMID 8896443.
Baumgrass R, Williamson MK, Price PA (1997). "Identification of peptide fragments generated by digestion of bovine and human osteocalcin with the lysosomal proteinases cathepsin B, D, L, H, and S." J. Bone Miner. Res. 12 (3): 447–55. doi:10.1359/jbmr.1997.12.3.447. PMID 9076588. S2CID 20815411.
Fujishima A, Imai Y, Nomura T, et al. (1997). "The crystal structure of human cathepsin L complexed with E-64". FEBS Lett. 407 (1): 47–50. doi:10.1016/S0014-5793(97)00216-0. PMID 9141479. S2CID 46288832.
Ménard R, Carmona E, Takebe S, et al. (1998). "Autocatalytic processing of recombinant human procathepsin L. Contribution of both intermolecular and unimolecular events in the processing of procathepsin L in vitro". J. Biol. Chem. 273 (8): 4478–84. doi:10.1074/jbc.273.8.4478. PMID 9468501.
Schick C, Pemberton PA, Shi GP, et al. (1998). "Cross-class inhibition of the cysteine proteinases cathepsins K, L, and S by the serpin squamous cell carcinoma antigen 1: a kinetic analysis". Biochemistry. 37 (15): 5258–66. doi:10.1021/bi972521d. PMID 9548757.
Estrada S, Nycander M, Hill NJ, et al. (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. PMID 9585570.
Halfon S, Ford J, Foster J, et al. (1998). "Leukocystatin, a new Class II cystatin expressed selectively by hematopoietic cells". J. Biol. Chem. 273 (26): 16400–8. doi:10.1074/jbc.273.26.16400. PMID 9632704.
External links
The MEROPS online database for peptidases and their inhibitors: C01.032
cathepsin, protein, that, humans, encoded, ctsl1, gene, protein, cysteine, cathepsin, lysosomal, cysteine, protease, that, plays, major, role, intracellular, protein, catabolism, ctslavailable, structurespdbhuman, uniprot, search, pdbe, rcsblist, codes1cjl, 1c. 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 CTSLAvailable structuresPDBHuman UniProt search PDBe RCSBList of PDB id codes1CJL 1CS8 1ICF 1MHW 2NQD 2VHS 2XU1 2XU3 2XU4 2XU5 2YJ2 2YJ8 2YJ9 2YJB 2YJC 3BC3 3H89 3H8B 3H8C 3HHA 3HWN 3IV2 3K24 3KSE 3OF8 3OF9 4AXL 4AXM 5F02 5I4HIdentifiersAliasesCTSL CATL CTSL1 MEP cathepsin LExternal IDsOMIM 116880 HomoloGene 129366 GeneCards CTSLGene location Human Chr Chromosome 9 human 1 Band9q21 33Start87 724 051 bp 1 End87 731 469 bp 1 RNA expression patternBgeeHumanMouse ortholog Top expressed instromal cell of endometriumislet of Langerhanspericardiumgallbladderupper lobe of left lungleft uterine tuberenal medullagastric mucosasmooth muscle tissueAchilles tendonn aMore reference expression dataBioGPSMore reference expression dataGene ontologyMolecular functionfibronectin binding cysteine type peptidase activity collagen binding histone binding serpin family protein binding peptidase activity protein binding cysteine type endopeptidase activity hydrolase activity proteoglycan binding serine type endopeptidase activityCellular componentextracellular region endolysosome lumen lysosomal lumen lysosome extracellular exosome nucleus extracellular space collagen containing extracellular matrix multivesicular body plasma membraneBiological processmacrophage apoptotic process antigen processing and presentation adaptive immune response antigen processing and presentation of exogenous peptide antigen via MHC class II extracellular matrix disassembly proteolysis toll like receptor signaling pathway cellular response to thyroid hormone stimulus collagen catabolic process proteolysis involved in cellular protein catabolic process regulation of keratinocyte differentiationSources Amigo QuickGOOrthologsSpeciesHumanMouseEntrez1514n aEnsemblENSG00000135047n aUniProtP07711Q9HBQ7n aRefSeq mRNA NM 001257971NM 001257972NM 001257973NM 001912NM 145918NM 001382757NM 001382758NM 001382766NM 001382767NM 001382768n aRefSeq protein NP 001244900NP 001244901NP 001244902NP 001903NP 666023NP 001369686NP 001369687NP 001369695NP 001369696NP 001369697NP 001244902 1n aLocation UCSC Chr 9 87 72 87 73 Mbn aPubMed search 2 n aWikidataView Edit Human Contents 1 Function 1 1 Viral entry 1 2 Inflammation 2 Interactions 3 Distribution 4 See also 5 References 6 Further reading 7 External linksFunction EditCathepsin 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 Inflammation Edit 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 Interactions EditCTSL1 has been shown to interact with Cystatin A 14 15 Distribution EditCathepsin L has been reported in many organisms including fish 16 birds mammals and sponges 17 See also EditCathepsin L2 also known as cathepsin V References Edit a b c GRCh38 Ensembl release 89 ENSG00000135047 Ensembl May 2017 Human PubMed Reference National Center for Biotechnology Information U S National Library of Medicine 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 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 a b Entrez Gene CTSL1 cathepsin L1 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 Barrett AJ Buttle DJ Mason RW 1988 Lysosomal cysteine proteinases ISI Atlas of Science Biochemistry 1 256 260 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 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 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 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 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 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 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 Estrada S Nycander M Hill N J Craven C J Waltho J P Bjork 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 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 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 Further reading EditSmith CG Smith MT Besch NF et al 1980 Effect of delta 9 tetrahydrocannabinol THC on female reproductive function Advances in the Biosciences 22 23 449 67 doi 10 1016 b978 0 08 023759 6 50040 8 ISBN 9780080237596 PMID 116880 Goretzki L Schmitt M Mann K et al 1992 Effective activation of the proenzyme form of the urokinase type plasminogen activator pro uPA by the cysteine protease cathepsin L FEBS Lett 297 1 2 112 8 doi 10 1016 0014 5793 92 80339 I PMID 1551416 S2CID 45421148 Dunn AD Crutchfield HE Dunn JT 1991 Thyroglobulin processing by thyroidal proteases Major sites of cleavage by cathepsins B D and L J Biol Chem 266 30 20198 204 doi 10 1016 S0021 9258 18 54909 7 PMID 1939080 Stearns NA Dong JM Pan JX et al 1991 Comparison of cathepsin L synthesized by normal and transformed cells at the gene message protein and oligosaccharide levels Arch Biochem Biophys 283 2 447 57 doi 10 1016 0003 9861 90 90666 M PMID 2275556 Ritonja A Popovic T Kotnik M et al 1988 Amino acid sequences of the human kidney cathepsins H and L FEBS Lett 228 2 341 5 doi 10 1016 0014 5793 88 80028 0 PMID 3342889 S2CID 45768546 Gal S Gottesman MM 1988 Isolation and sequence of a cDNA for human pro cathepsin L Biochem J 253 1 303 6 doi 10 1042 bj2530303 PMC 1149292 PMID 3421948 Johnson DA Barrett AJ Mason RW 1986 Cathepsin L inactivates alpha 1 proteinase inhibitor by cleavage in the reactive site region J Biol Chem 261 31 14748 51 doi 10 1016 S0021 9258 18 66935 2 PMID 3490478 Mason RW Walker JE Northrop FD 1987 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 240 2 373 7 doi 10 1042 bj2400373 PMC 1147428 PMID 3545185 Joseph L Lapid S Sukhatme V 1987 The major ras induced protein in NIH3T3 cells is cathepsin L Nucleic Acids Res 15 7 3186 doi 10 1093 nar 15 7 3186 PMC 340927 PMID 3550705 Kargel HJ Dettmer R Etzold G et al 1982 Action of rat liver cathepsin L on glucagon Acta Biol Med Ger 40 9 1139 43 PMID 7340337 Bevec T Stoka V Pungercic G et al 1996 Major histocompatibility complex class II associated p41 invariant chain fragment is a strong inhibitor of lysosomal cathepsin L J Exp Med 183 4 1331 8 doi 10 1084 jem 183 4 1331 PMC 2192513 PMID 8666891 Coulombe R Grochulski P Sivaraman J et al 1996 Structure of human procathepsin L reveals the molecular basis of inhibition by the prosegment EMBO J 15 20 5492 503 doi 10 1002 j 1460 2075 1996 tb00934 x PMC 452294 PMID 8896443 Baumgrass R Williamson MK Price PA 1997 Identification of peptide fragments generated by digestion of bovine and human osteocalcin with the lysosomal proteinases cathepsin B D L H and S J Bone Miner Res 12 3 447 55 doi 10 1359 jbmr 1997 12 3 447 PMID 9076588 S2CID 20815411 Fujishima A Imai Y Nomura T et al 1997 The crystal structure of human cathepsin L complexed with E 64 FEBS Lett 407 1 47 50 doi 10 1016 S0014 5793 97 00216 0 PMID 9141479 S2CID 46288832 Menard R Carmona E Takebe S et al 1998 Autocatalytic processing of recombinant human procathepsin L Contribution of both intermolecular and unimolecular events in the processing of procathepsin L in vitro J Biol Chem 273 8 4478 84 doi 10 1074 jbc 273 8 4478 PMID 9468501 Schick C Pemberton PA Shi GP et al 1998 Cross class inhibition of the cysteine proteinases cathepsins K L and S by the serpin squamous cell carcinoma antigen 1 a kinetic analysis Biochemistry 37 15 5258 66 doi 10 1021 bi972521d PMID 9548757 Estrada S Nycander M Hill NJ et al 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 PMID 9585570 Halfon S Ford J Foster J et al 1998 Leukocystatin a new Class II cystatin expressed selectively by hematopoietic cells J Biol Chem 273 26 16400 8 doi 10 1074 jbc 273 26 16400 PMID 9632704 External links EditThe MEROPS online database for peptidases and their inhibitors C01 032 Cathepsin L at the US National Library of Medicine Medical Subject Headings MeSH Portal Biology This article on a gene on human chromosome 9 is a stub You can help Wikipedia by expanding it vte Retrieved from https en wikipedia org w index php title Cathepsin L1 amp oldid 1092828254, wikipedia, wiki, book, books, library,
