Cystatin 4, also known as Cystatin-S, Salivary acidic protein 1, Cystatin-SA-III, and CST4, is a member of the cystatin superfamily. This family of proteins is characterized by their ability to inhibit cysteine proteases, which are enzymes that break down proteins by cleaving peptide bonds. Cystatin 4 is a secreted protein that plays a crucial role in various physiological processes.
Cystatin 4 is predominantly expressed in submandibular and sublingual saliva, but it is not found in parotid saliva . Additionally, it is present in other bodily fluids such as tears, urine, and seminal fluid . This widespread distribution suggests that Cystatin 4 has multiple functions in different tissues and organs.
The cystatin superfamily includes proteins with multiple cystatin-like sequences. Some members of this family are active cysteine protease inhibitors, while others have lost or never acquired this inhibitory activity . Cystatin 4 belongs to the type 2 cystatins, which are a class of cysteine proteinase inhibitors found in various human fluids and secretions .
Cystatin 4 strongly inhibits enzymes such as papain and ficin, partially inhibits stem bromelain and bovine cathepsin C, but does not inhibit porcine cathepsin B or clostripain . This selective inhibition is important for regulating proteolytic activity in different physiological contexts.
Recombinant human Cystatin 4 is produced using DNA sequences encoding the human CST4 gene. The recombinant protein is typically expressed in host cells such as HEK293 cells and is purified to high levels of purity . The recombinant protein is often tagged with a polyhistidine tag to facilitate purification and detection .
Recombinant Cystatin 4 is used in various research applications to study its inhibitory effects on cysteine proteases and its role in different physiological processes. It is also used in the development of therapeutic agents targeting protease-related diseases.