Furin Antibody

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

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.

We have publications tested in 2 confirmed species: Human, Primate.

We have publications tested in 1 application: WB.

Showing Publications 1 - 2 of 2.

Publications using NB100-1903	Applications	Species
Mezger MC, Conzelmann C, Weil T et al. Inhibitors of Activin Receptor-like Kinase 5 Interfere with SARS-CoV-2 S-Protein Processing and Spike-Mediated Cell Fusion via Attenuation of Furin Expression Viruses 2022-06-15 [PMID: 35746781] (WB, Human, Primate)	WB	Human, Primate
Minjin Jeong, Karen E. Ocwieja, Dongjun Han, P. Ashley Wackym, Yichen Zhang, Alyssa Brown, Cynthia Moncada, Andrea Vambutas, Theodore Kanne, Rachel Crain, Noah Siegel, Valerie Leger, Felipe Santos, D. Bradley Welling, Lee Gehrke, Konstantina M. Stankovic Direct SARS-CoV-2 infection of the human inner ear may underlie COVID-19-associated audiovestibular dysfunction Communications Medicine 2021-10-29 [PMID: 34870285]

Images	Ratings	Applications	Species	Date	Details
Enlarge	5 reviewed by: Verified Customer	ICC	Equine	05/13/2017	View Summary Application Immunocytochemistry Sample Tested Placental tissue Species Equine Comments Comments 1:200 dilution. Heat based antigen retrieval using EDTA based solution. No staining on negative when the primary antibody was omitted.

Array NB100-1903

• Furin Antibodies
• Furin ELISA Kits
• Furin Lysate
• Furin Protein
• Furin Proteins and Enzymes
• Furin ELISA