Cathepsin L

Cathepsin L is a lysosomal cysteine protease that plays a major role in intracellular protein catabolism, and is potent in degrading collagen, laminin, elastin, as well as alpha-1 protease inhibitor and other structural proteins of basement membranes. It is secreted by liver flukes at all stages of their development in the mammalian host, are believed to play important roles in facilitating parasite migration (tissue degradation), feeding and immuno-evasion. Like many proteases, Cathepsin L is synthesized as an inactive preproenzyme, and cleavage of the 96-residue proregion is necessary to generate the fully active 221-residue mature enzyme. Studies have demonstrated that cleavage of the proregion occur autocatalytically under acidic conditions. The enzyme takes part in nutrient acquisition by catabolizing host proteins to absorbable peptides, facilitates the migration of the parasite through the host intestine and liver by cleaving interstitial matrix proteins such as fibronectin, laminin and native collagen and is implicated in the inactivation of host immune defenses by cleaving immunoglobulins. Recently, Cathepsin L has been shown to suppress Th1 immune response in infected laboratory animals making them susceptible to concurrent bacterial infections. Cathepsin L is synthesized in large amounts and secreted by many malignantly transformed cells, and induced by growth factors and tumor promoters. In addition to its role in protein degradation, evidence has accumulated for the participation of Cathepsin L in various physiological and pathological processes, such as tumor invasion and metastasis, bone resorption, spermatogenesis, and arthritis. Accordingly, Cathepsin L may prove useful as a diagnostic or prognostic marker of human tumor malignancy.

Cathepsin L Related Areas

Enzyme>>Protease & Regulator>>Cysteine Protease & Regulator>>Cathepsin Family>>Cathepsin L/CTSL/CTSL1

Cancer>>Angiogenesis>>Cathepsin Family>>Cathepsin L/CTSL/CTSL1

Immunology>>Innate Immunity>>Lysosomal Enzyme>>Cathepsin Family>>Cathepsin L/CTSL/CTSL1

Cathepsin L Alternative Names

Cathepsin L, Cathepsin L1, CTSL, CTSL1, CATL, FLJ31037, MEP [Homo sapiens]

Cathepsin L, Cathepsin L1, Ctsl, Ctsl1, 1190035F06Rik, MEP, fs, nkt [Mus musculus]

Summaries for Cathepsin L

Entrez Gene summary for Cathepsin L:

The protein encoded by this gene is a lysosomal cysteine proteinase that plays a major role in intracellular protein catabolism. 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. Multiple alternatively spliced transcript variants have been found for this gene.

OMIM - description for Cathepsin L:

Cathepsin L is a lysosomal cysteine proteinase with a major role in intracellular protein catabolism. It also shows the most potent collagenolytic and elastinolytic activity in vitro of any of the cathepsins. Cathepsin L proteolytically inactivates alpha-1 protease inhibitor (107400), a major controlling element of human neutrophil elastase (130130) activity in vivo. Cathepsin L has been implicated in pathologic processes including myofibril necrosis in myopathies and in myocardial ischemia, and in the renal tubular response to proteinuria

Wikipedia summary for Cathepsin L:

Cathepsin L1 is a protein that in humans is encoded by the CTSL1 gene.The protein encoded by this gene is a lysosomal cysteine proteinase that plays a major role in intracellular protein catabolism. 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

Human Cathepsin L Protein General Information

 

• Protein names: Recommended name: Cathepsin L1
• Sequence length: 333 AA.
• Domain: Signal
• Sequence similarities: Belongs to the peptidase C1 family.
• Catalytic activity: Specificity close to that of papain. As compared to cathepsin B, cathepsin L exhibits higher activity toward protein substrates, but has little activity on Z-Arg-Arg-NHMec, and no peptidyl-dipeptidase activity.
• Subunit structure: Dimer of a heavy and a light chain linked by disulfide bonds.
• Subcellular location: Lysosome.

General information above from UniProt

Function for Cathepsin L Protein

UniProtKB:

Important for the overall degradation of proteins in lysosomes.

Genatlas:

• cysteine proteinase cleaving collagen and elastin
• Cathepsin L is involved in matrix degradation during endochondral ossification
• Cathepsin L has a critical role in the integration of circulating endothelial progenitor cells into ischemic tissue and is required for endothelial progenitor cells -mediated neovascularization
• Cathepsin L plays a potent role in degrading collagen, laminin, and implicated in tumor invasion and metastasis
• Cathepsin L plays a major role in intracellular protein catabolism
• functioning as a prohormone -processing enzyme for production of the enkephalin peptide neurotransmitter(through secretory vesicules)
• Cathepsin L plays a role in peptide generation for MHC class 2 presentation
• Cathepsin L functions as a proneuropeptide processing enzyme for the conversion of proenkephalin to mature (Met)enkephalin, an opioid peptide neurotransmitter and hormone, as a distinct cysteine protease pathway for producing the enkephalin member of neuropeptides
• Cathepsin L plays an intracellular role in normal intestinal epithelial polarization and initiation of neoplasia
• Cathepsin L role in the degradation of the matrix protein fibronectin, insulin receptor (IR) and insulin-like growth factor-1 receptor (IGF1R), essential molecules for adipogenesis and glucose metabolism
• Cathepsin L may play important roles during normal placentation and in the etiology of pre-eclampsia

Homology for human Cathepsin L

• homolog to murine Ctsl

Drugs for Cathepsin L

Target	Drug Name	Disease	Drug Status
Cathepsin L	CRA-028129	Psoriasis and Psoriatic Disorders Discontinued in	Discontinued in Phase I

Drugs for Cathepsin L from TTD (Therapeutic Targets Database)