Furin (also known as FUR, PACE, PCSK3, and SCP1) is a ubiquity expressed, calcium-dependent serine protease that belongs to the subtilisin-like proprotein convertase (PC) family (1). Furin is synthesized as a 794-amino acid type-I transmembrane protein (1). Like other PC family members, furin shares structural similarity which includes a heterogeneous ~10 kDa amino terminal proregion, a ~55 kDa highly conserved subtilisin-like catalytic domain, and a carboxylterminal domain that is heterogeneous and varies in length and sequence between different PC family members (2). Furin plays an important role in embryogenesis and assists in the maturation of proprotein substrates (1,3). As a protease, furin cleaves and activates over 150 mammalian, viral, and bacterial substrates (3). These substrates include growth factors, receptors, hormones, cytokines, and adhesion molecules (1, 3). Furin processes these proproteins in secretory pathway compartments by cleaving at the carboxyl-terminus of the consensus sequence RX(K/R)R (where X is any amino acid) (1). Furin is localized to the trans-Golgi-network by the acidic peptide sequence C771PSDSEEDEG780 where phosphorylation of the serine residues regulates the intracellular trafficking. Another unique signaling domain is the hydrophobic motif Y759KGL762 that modulates endocytosis from the cell surface. The theoretical molecular weight of furin is 87 kDa; however, the observed molecular weight may vary as post-translational modifications, like glycosylation, cause the pre-pro furin to run at 110-104 kDa, the mature furin at 98-95 kDa, and the shed furin at 90 kDa (4).

Proteolytic cleavage regulates several physiological processes in both health and disease (3). Abnormal activity or mutations in proteases, including furin, is associated with pathologies and diseases including cancer, cardiovascular disorders, diabetes, inflammation, neurological diseases, and autoimmune diseases (3). As mentioned above, furin also acts upon bacterial substrates, including anthrax and Shiga toxin, and many virus families such as Herpes-, Flavi-, and Corona-, leading to host infections. Furthermore, the novel coronavirus disease 2019 (COVID-19) is caused by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) present with a S-spike protein that is cleaved by PCs, including furin, at the S1/S2 cleavage site (5, 6). The cleavage allows the SARS-CoV-2 to then attach to the angiotensin-converting enzyme 2 (ACE2) receptor via the S1 domain and the cellular membrane via the S2 domain (5, 6). Although COVID-19 patients mostly present with respiratory symptoms, a variety of other systems are affected including cardiovascular, gastrointestinal (GI), and the liver (5-7). It is suggested that the S1/furin/ACE2 interaction promotes SARS-CoV-2 infection leading to the harmful symptoms and reactions in patients (5, 6). Cardiovascular disease is a common comorbidity in patients, along with hypertension, myocardial damage, and heart palpitations (Ming). Further evidence of furin being a risk factor for infection is the high levels of furin present in the blood of heart failure patients (5). Similarly, the small bowel may be another interaction site for infection as it is rich in furin and the intestinal enterocytes have many ACE2 receptors (6). Furin is also highly expressed in the liver and hepatocytes and cholangiocytes of the liver present ACE2 receptors (3, 7). Studies have shown that up one-third of COVID-19 patients experience GI symptoms which range from diarrhea and loss of appetite to abdominal cramping and bloody stool (6, 7). Additionally, some patients displayed abnormal liver enzyme levels (7). It has been suggested that a possible therapeutic strategy for treating those infected with SARS-CoV-2 is pharmacologically or immunologically modulating furin or ACE2 binding sites to combat COVID-19 infection (3, 5).

References

1. Thomas, G. (2002). Furin at the cutting edge: from protein traffic to emryogenesis and disease. Nature Rev. Mol. Cell Biol. https://doi.org/10.1038/nrm934

2. Zhou A., Paquet, L., & Mains, R.E. (1995). Structural elements that direct specific processing of different mammalian subtilisin-like prohormone convertases. J Biol Chem. https://doi.org/10.1074/jbc.270.37.21509

3. Braun E., & Sauter, D. (2019). Furin-mediated protein processing in infectious diseases and cancer. Clin Transl Immunology. https://doi:10.1002/cti2.1073

4. Atlas of Genetics and Cytogenetics in Oncology and Haematology, FURIN

5. Ming, Y. & Qiang, L. (2020). Involvement of Spike Protein, Furin, and ACE2 in SARS-CoV-2-Related Cardiovascular Complications. SN Compr. Clin. Med. https://doi.org/10.1007/s42399-020-00400-2

6. Monkemuller, K., Fry, L., & Rickes, S. (2020). COVID-19, coronavirus, SARS-CoV-2 and the small bowel. Rev Esp Enferm Dig. https://doi:10.17235/reed.2020.7137/2020

7. Agarwal, A., Chen, A., Ravindran, N., To, C., & Thuluvath, P.J. (2020). Gastrointestinal and Liver Manifestations of COVID-19. J Clin Exp Hepatol. https://doi:10.1016/j.jceh.2020.03.001

Alternate Names

FUR, PACE, PCSK3, SPC1

Gene Symbol

FURIN

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Product Specific Notices for Furin Antibody (MM0298-4G31) [Alexa Fluor® 700]

Alexa Fluor (R) products are provided under an intellectual property license from Life Technologies Corporation. The purchase of this product conveys to the buyer the non-transferable right to use the purchased product and components of the product only in research conducted by the buyer (whether the buyer is an academic or for-profit entity). The sale of this product is expressly conditioned on the buyer not using the product or its components, or any materials made using the product or its components, in any activity to generate revenue, which may include, but is not limited to use of the product or its components: (i) in manufacturing; (ii) to provide a service, information, or data in return for payment; (iii) for therapeutic, diagnostic or prophylactic purposes; or (iv) for resale, regardless of whether they are resold for use in research. For information on purchasing a license to this product for purposes other than as described above, contact Life Technologies Corporation, 5791 Van Allen Way, Carlsbad, CA 92008 USA or outlicensing@lifetech.com. This conjugate is made on demand. Actual recovery may vary from the stated volume of this product. The volume will be greater than or equal to the unit size stated on the datasheet.

This product is for research use only and is not approved for use in humans or in clinical diagnosis. Primary Antibodies are guaranteed for 1 year from date of receipt.

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Furin Antibody (MM0298-4G31) [Alexa Fluor® 700]

Novus Biologicals, part of Bio-Techne | Catalog # NBP2-12321AF700

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Additional Furin Products

Product Documents for Furin Antibody (MM0298-4G31) [Alexa Fluor® 700]

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Product Specific Notices for Furin Antibody (MM0298-4G31) [Alexa Fluor® 700]

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