Protein: Procathepsin L (EC 3.4.22.15) (Cathepsin L1) (Major excreted protein) (MEP) [Cleaved into: Cathepsin L; Cathepsin L heavy chain; Cathepsin L light chain] (P07711)
Organism: Homo sapiens (Human)
Function: 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. 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).
Subcellular location: Lysosome {ECO:0000250|UniProtKB:P06797}. Apical cell membrane {ECO:0000250|UniProtKB:P06797}; Peripheral membrane protein {ECO:0000250|UniProtKB:P06797}; Extracellular side {ECO:0000250|UniProtKB:P06797}. Cytoplasmic vesicle, secretory vesicle, chromaffin granule {ECO:0000250|UniProtKB:P25975}. Secreted, extracellular space {ECO:0000250|UniProtKB:P06797}. Secreted {ECO:0000250|UniProtKB:P06797}. Note=Localizes to the apical membrane of thyroid epithelial cells. Released at extracellular space by activated dendritic cells and macrophages. {ECO:0000250|UniProtKB:P06797}.; SUBCELLULAR LOCATION: [Isoform 2]: Nucleus {ECO:0000269|PubMed:15099520}. Note=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, with higher levels during S phase (PubMed:15099520). {ECO:0000269|PubMed:15099520}.
Interaction partners:
- HLA class II histocompatibility antigen gamma chain
- Cystatin-A
- Cathepsin B
- Cystatin-B
- Cystatin-F
- Apoptosis regulator Bcl-2
- Legumain
- Bcl-2-like protein 1
- BH3-interacting domain death agonist
- Cathepsin S
Sequence:
MNPTLILAAFCLGIASATLTFDHSLEAQWTKWKAMHNRLYGMNEEGWRRAVWEKNMKMIELHNQEYREGKHSFTMAMNAFGDMTSEEFRQVMNGFQNRKPRKGKVFQEPLFYEAPRSVDWREKGYVTPVKNQGQCGSCWAFSATGALEGQMFRKTGRLISLSEQNLVDCSGPQGNEGCNGGLMDYAFQYVQDNGGLDSEESYPYEATEESCKYNPKYSVANDTGFVDIPKQEKALMKAVATVGPISVAIDAGHESFLFYKEGIYFEPDCSSEDMDHGVLVVGYGFESTESDNNKYWLVKNSWGEEWGMGGYVKMAKDRRNHCGIASAASYPTV