Serpin Peptidase Inhibitor, Clade B Member 4 (SERPINB4), also known as Squamous Cell Carcinoma Antigen 2 (SCCA2), is a member of the serpin family of serine protease inhibitors. This protein is encoded by the SERPINB4 gene located on chromosome 18q21.33 . SERPINB4 is highly expressed in many tumor cells and plays a significant role in modulating the host immune response against tumor cells .
SERPINB4 belongs to the ovalbumin family of serpins, which are characterized by their ability to inhibit serine proteases through a unique mechanism involving a large conformational change . This protein is composed of 390 amino acids and shares 92% amino acid identity with its paralog, SERPINB3 . The reactive site of SERPINB4 contains a leucine residue, which acts as a pseudosubstrate for the target protease .
The primary function of SERPINB4 is to inhibit proteases, particularly granzyme M, an enzyme that kills tumor cells . By inhibiting granzyme M, SERPINB4 helps tumor cells evade the immune response, contributing to tumor progression and metastasis .
SERPINB4 is clinically significant as a tumor marker for squamous cell carcinoma (SCC), especially in cancers of the cervix, head and neck, lung, and esophagus . Elevated levels of SERPINB4 are detected in the plasma of patients with these cancers, and its presence is correlated with more aggressive tumors . The protein is detected in the cytoplasm of normal and some malignant squamous cells, while its mRNA is found in the basal and subbasal layers of squamous epithelium .
Human recombinant SERPINB4 is produced using recombinant DNA technology, which involves inserting the SERPINB4 gene into a suitable expression system, such as bacteria or mammalian cells. This allows for the large-scale production of the protein for research and therapeutic purposes. Recombinant SERPINB4 retains the functional properties of the native protein and is used in various studies to understand its role in cancer biology and potential therapeutic applications.