Cathepsin L1

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]

CTSL
Available structures PDB Human UniProt search: PDBe RCSB List of PDB id codes 1CJL, 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, 5I4H
Identifiers
Aliases	CTSL, CATL, CTSL1, MEP, cathepsin L
External IDs	OMIM: 116880; HomoloGene: 129366; GeneCards: CTSL; OMA:CTSL - orthologs
Gene location (Human) Chr. Chromosome 9 (human)[1] Band 9q21.33 Start 87,724,051 bp[1] End 87,731,469 bp[1]
RNA expression pattern Bgee Human Mouse (ortholog) Top expressed in stromal cell of endometrium decidua islet of Langerhans pericardium gallbladder upper lobe of left lung left uterine tube renal medulla muscle layer of sigmoid colon gastric mucosa n/a More reference expression data BioGPS More reference expression data
Gene ontology Molecular function fibronectin 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 activity Cellular component extracellular region endolysosome lumen lysosomal lumen lysosome extracellular exosome nucleus extracellular space collagen-containing extracellular matrix multivesicular body plasma membrane Biological process macrophage 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 differentiation Sources:Amigo / QuickGO
Orthologs Species Human Mouse Entrez 1514 n/a Ensembl ENSG00000135047 n/a UniProt P07711 Q9HBQ7 n/a RefSeq (mRNA) NM_001257971 NM_001257972 NM_001257973 NM_001912 NM_145918 NM_001382757 NM_001382758 NM_001382766 NM_001382767 NM_001382768 n/a RefSeq (protein) NP_001244900 NP_001244901 NP_001244902 NP_001903 NP_666023 NP_001369686 NP_001369687 NP_001369695 NP_001369696 NP_001369697 NP_001244902.1 n/a Location (UCSC) Chr 9: 87.72 – 87.73 Mb n/a PubMed search [2] n/a
Wikidata
View/Edit Human

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.^[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-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

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

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

Distribution

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

See also

• Cathepsin L2 (also known as cathepsin V)