CTSF Human

Cathepsin-F is a lysosomal cysteine protease that belongs to the papain family of proteases. It is encoded by the CTSF gene and is involved in protein degradation within the lysosome. Cathepsin-F has been implicated in various physiological and pathological processes, including tumor progression and immune response regulation.

Cathepsin-F was first cloned from a human skeletal muscle cDNA library. The nucleotide sequence encodes a polypeptide of 302 amino acids, which includes an 88-residue propeptide and a 214-residue mature protein . The precursor polypeptide of human recombinant cathepsin-F, produced in Pichia pastoris, is processed to its active mature form either autocatalytically or by incubation with pepsin .

Cathepsin-F shares significant homology with other cathepsins, particularly cathepsin-W, with which it shares 58% sequence homology . It also shows 42-43% homology with cathepsins L, K, S, H, and O, and 38% homology with cathepsin-B . The presence of the “ERFNAQ” motif in the propeptides of cathepsin-F and cathepsin-W, along with their conserved genomic organization and chromosomal localization, suggests that they form a novel subset of cathepsin proteases known as “cathepsin F-like” proteases .

Northern blot analysis has shown that cathepsin-F is highly expressed in the heart, skeletal muscle, brain, testis, and ovary . Moderate expression levels are observed in the prostate, placenta, liver, and colon, while no detectable expression is found in peripheral leukocytes and thymus .

Mature cathepsin-F exhibits high enzymatic activity with specific activities comparable to those of cathepsin-L . It has a broad pH optimum between 5.2 and 6.8, indicating its function in acidic cellular compartments . However, its pH stability at cytosolic pH (7.2) is short, with a half-life of approximately 2 minutes .

Cathepsin-F is unique among cathepsins as its open reading frame does not encode a signal sequence, suggesting that it is targeted to the lysosomal compartment via an N-terminal signal peptide-independent lysosomal targeting pathway . This protease plays a role in protein degradation and has been implicated in tumor progression . Additionally, cathepsin-F may regulate immune responses in non-small cell lung cancer (NSCLC), where its expression is correlated with immune cell molecular markers and immunomodulators .