Furin recognizable “prrar” motif is ubiquitously present in nature in non-viral proteins

Furin is a calcium-dependent endopeptidase. It is found in all vertebrates and many invertebrates. It is localized in the Golgi apparatus, and in the extra cellular space. It functions in the biosynthesis of a diverse group of cellular proteins that includes hormones, growth factors, matrix metalloproteases, and coagulation factors. Additionally many viral pathogens have co-evolved exploiting host cell Furin in the cleavage of their coat proteins and enhancing the viral fusion with the host cell membrane. Furin activates specific proteins by cleaving them at paired basic amino acid site containing the minimal structure of Arg-X-[Arg/Lys]-Arg, where X represents any amino acid. A 20 amino acid definition of the Furin cleavage site was later introduced based on the crystal structure of Furin. Lately, Furin has received much attention, because of the presence of a four amino acid insert “prra” in the spike protein of the Covid-19 pathogen SARS-CoV-2. Together with an adjacent arginine residue the insert created a polybasic “prrar” motif that is favored by Furin for cleavage. Many laboratories have confirmed the involvement of Furin-mediated cleavage of the spike protein at the “prrar” site in the pathogenesis of SARS-CoV-2. The origins of “prra” insert is unclear because so far no known protein is found to carry “prra”, although many proteins contain other versions of the Furin cleavage site.” In this study using a combination of BLAST and a previously described software program, compare, the author has identified a large number of GenBank annotated non-viral proteins carrying “prrar” motifs. The search resulted in the identification of several proteins containing “prrar” motif both from bacteria, and higher animals. Interestingly none of the proteins identified are annotated in the GenBank in the context of Furin studies. Therefore the information obtained is new to the investigators. In this report the data are compiled into tables with all the essential information listed for each protein. The probability of these proteins to be good substrates for Furin is discussed in the light of published observations on the effects of various amino acids present in the vicinity of the Furin cleavable sites.