SERPINB3 gene

SERPINB3 (SERPINB3 stands for: Serpin Family B Member 3) is a protein-coding gene located on chromosome 18q21.33. SERPINB3 and SERPINB4 are evolutionary duplicated serine/cysteine protease inhibitors. As papain-like cysteine protease inhibitors, they can modulate the host's immune response against tumor cells. They are localized in cytoplasmic vesicles, extracellular exosomes and in the cell nucleus.

SERPINB3 also acts as an inhibitor of UV-induced apoptosis by suppressing the activity of c-Jun NH(2)-terminal kinase (JNK1). Enables protease binding activity and viral receptor activity (Vidalino L et al. 2009). It is also involved in several processes, including autocrine signaling, paracrine signaling and regulation of cellular protein metabolism.

Diseases associated with SERPINB3 include lung cancer, hepatocellular carcinoma and squamous cell carcinoma (Pontisso P 2014). Mechanisms of SERPINB3-induced tumor growth promotion include inhibition of natural killer cell infiltration into the tumor, upregulation of the Myc oncogene and its function as a Ras-responsive factor (Pontisso P 2014). By binding to respiratory complex I, SERPINB3 can also contribute to the resistance of tumor cells to antineoplastic drugs and protect the cells from the prooxidative effects of chemotherapeutic agents.

Mutations in SERPINB3 have been described as predisposing risk factors for both AOID(adult-onset immunodeficiency syndrome) and GPP(generalized pustular psoriasis). The skin of patients with GPP and AOID who carry SERPINB3 mutations show overexpression of SERPINB3 and SERPINA1 (Kantaputra P et al. 2023). Among other things, this is evidence that GPP and psoriasis are diseases with different genetic backgrounds (Bachelez H et al. 2022).

Genomic analyses show that SERPINB3 and SERPINB34 were encoded as paralogous genes from independent loci resulting from a tandem gene duplication. Although the amino acid sequences of the two molecules are 92 % identical, they differ in the reactive center loop (RCL), which includes a hinge region and catalytic sequences, resulting in altered substrate specificity (Sun Y et al. 2017).

1. Bachelez H et al. (2022) Generalized pustular psoriasis is a disease distinct from psoriasis vulgaris: evidence and expert opinion. Expert Rev Clin Immunol 18:1033-1047.
2. Kantaputra P et al. (2023) SERPINB3, Adult-Onset Immunodeficiency, and Generalized Pustular Psoriasis. Genes (Basel) 14:266.
3. Pontisso P (2014) Role of SERPINB3 in hepatocellular carcinoma. Ann Hepatol 13:722-727.
4. Sun Y et al. (2017) SERPINB3 and B4: From biochemistry to biology. Semin Cell Dev Biol 62:170-177.
5. Vidalino L et al. (2009) SERPINB3, apoptosis and autoimmunity. Autoimmun Rev 9:108-112