Ctsl

CTSL (Cathepsin L) is a Protein Coding gene. Diseases associated with CTSL include Tracheal Cancer and Eccrine Acrospiroma. Among its related pathways are Bacterial infections in CF airways and Primary Focal Segmental Glomerulosclerosis FSGS. Gene Ontology (GO) annotations related to this gene include histone binding and cysteine-type peptidase activity. An important paralog of this gene is CTSV.

Cathepsin L

Thiol protease important for the overall degradation of proteins in lysosomes (Probable). Plays a critical for normal cellular functions such as general protein turnover, antigen processing and bone remodeling. Involved in the solubilization of cross-linked TG/thyroglobulin and in the subsequent release of thyroid hormone thyroxine (T4) by limited proteolysis of TG/thyroglobulin in the thyroid follicle lumen (By similarity).

In neuroendocrine chromaffin cells secretory vesicles, catalyzes the prohormone proenkephalin processing to the active enkephalin peptide neurotransmitter (By similarity).

In thymus, regulates CD4+ T cell positive selection by generating the major histocompatibility complex class II (MHCII) bound peptide ligands presented by cortical thymic epithelial cells. Also mediates invariant chain processing in cortical thymic epithelial cells (By similarity).

Major elastin-degrading enzyme at neutral pH. Accumulates as a mature and active enzyme in the extracellular space of antigen presenting cells (APCs) to regulate degradation of the extracellular matrix in the course of inflammation (By similarity).

Secreted form generates endostatin from COL18A1 (PubMed:10716919).

Critical for cardiac morphology and function. Plays an important role in hair follicle morphogenesis and cycling, as well as epidermal differentiation (By similarity).

Required for maximal stimulation of steroidogenesis by TIMP1 (By similarity).

Isoform 2:
Functions in the regulation of cell cycle progression through proteolytic processing of the CUX1 transcription factor (PubMed:15099520).

Translation initiation at downstream start sites allows the synthesis of isoforms that are devoid of a signal peptide and localize to the nucleus where they cleave the CUX1 transcription factor and modify its DNA binding properties (PubMed:15099520).

(Microbial infection) Facilitates human coronaviruses SARS-CoV and SARS-CoV-2 infections via proteolysis of coronavirus spike (S) glycoproteins in lysosome for entry into host cell (PubMed:32142651, PubMed:32221306, PubMed:16339146, PubMed:18562523).

Proteolysis within lysosomes is sufficient to activate membrane fusion by coronaviruses SARS-CoV and EMC (HCoV-EMC) S as well as Zaire ebolavirus glycoproteins (PubMed:16081529, PubMed:26953343, PubMed:18562523).

Adaptive immune response Source: UniProtKB
Antigen processing and presentation Source: UniProtKB
Antigen processing and presentation of exogenous peptide antigen via MHC class II Source: Reactome
Antigen processing and presentation of peptide antigen Source: UniProtKB
CD4-positive, alpha-beta T cell lineage commitment Source: UniProtKB
Cellular response to thyroid hormone stimulus Source: UniProtKB
Collagen catabolic process Source: UniProtKB
Elastin catabolic process Source: UniProtKB
Enkephalin processing Source: UniProtKB
Extracellular matrix disassembly Source: Reactome
Fusion of virus membrane with host endosome membrane Source: UniProtKB
Fusion of virus membrane with host plasma membrane Source: UniProtKB
Immune response Source: GO_Central
Macrophage apoptotic process Source: BHF-UCL
Protein autoprocessing Source: UniProtKB
Proteolysis Source: UniProtKB
Proteolysis involved in cellular protein catabolic process Source: BHF-UCL
Receptor-mediated endocytosis of virus by host cell Source: UniProtKB
Regulation of keratinocyte differentiation Source: Reactome
Toll-like receptor signaling pathway Source: Reactome
Viral entry into host cell Source: UniProtKB
Zymogen activation Source: UniProtKB

Extracellular space; Secreted; Lysosome; Apical cell membrane; Chromaffin granule. Localizes to the apical membrane of thyroid epithelial cells. Released at extracellular space by activated dendritic cells and macrophages.
Isoform 2: Nucleus. Translation initiation at downstream start sites allows the synthesis of isoforms that are devoid of a signal peptide and do not transit through the endoplasmic reticulum to localize to the nucleus (PubMed:15099520). Nuclear location varies during the cell cycle, whith higher levels during S phase (PubMed:15099520).

During export along the endocytic pathway, pro-CTSL undergoes several proteolytic cleavages to generate the CTSL single-chain and two-chain mature forms, composed of a heavy chain linked to a light chain by disulfide bonds (By similarity). Autocleavage; produces the single-chain CTSL after cleavage of the propeptide. The cleavage can be intermolecular (PubMed:9468501).