Disease relevance of Fur1

• By using recombinant vaccinia viruses that express each of the dfurin proteins, we investigated the potential effect of the C-terminal domain on their catalytic specificities [1].
• The highest degree of homology is found in a region that contains a furin cleavage site in the baculovirus proteins and an adjacent sequence that has the properties of a fusion peptide [2].

High impact information on Fur1

• By comparative nucleotide sequence analysis of Dfur1 genomic and cDNA clones, 10 coding exons were identified and, together with Northern blot analysis using exon-specific probes, evidence was obtained that the four transcripts are generated by alternative splicing and polyadenylation [3].
• Generation of structural and functional diversity in furin-like proteins in Drosophila melanogaster by alternative splicing of the Dfur1 gene [3].
• The apparently complete open reading frames of three Dfur1 cDNAs revealed that these coded for three furin-like proteins, Dfurin1 (892 residues), Dfurin1-CRR (1101 residues) and Dfurin1-X (1269 residues), which possessed common but also unique structural domains [3].
• The data suggest a possible role for a membrane bound, furin-like protease in the mechanism of defense gene signaling by systemin [4].
• In adults, dKLIP-1 transcripts were detected in cortical regions of the CNS and fat body [5].

Biological context of Fur1

• From overlapping Dfur1 cDNA clones, a composite cDNA could be constructed and analysis of its nucleotide sequence revealed the coding sequence for a protein of 899 amino acid residues [6].
• This protein, designated Dfurin1, exhibited striking sequence homology to human furin and contained the same protein domains except for the cysteine-rich region [6].
• Furthermore, unlike human furin, Dfurin1 possessed an extended amino-terminal region in which a potential transmembrane anchor was present [6].
• To investigate whether or not alternative splicing might be a mechanism by which in Drosophila melanogaster diversity is generated in endoproteases of the novel eukaryotic family of subtilisin-like proprotein processing enzymes, we determined structural and functional characteristics of the Dfur1 gene [3].
• The predicted Dm-cF protein sequence lacks a furin cleavage site, and transiently expressed Dm-cF showed no protein cleavage and no detectable membrane fusion activity [7].

Anatomical context of Fur1

• Immunofluorescence studies show that Spn4A is localized in the endoplasmic reticulum (ER), suggesting that the inhibitor is an interesting tool for investigating the cellular mechanisms regulating furin and for the design of agents controlling prohormone convertases [8].
• Moreover, we find that processing of Notch in the Golgi by the furin protease is unaffected in Dps mutants and that Notch is present and may even accumulate on the plasma membrane of neuroblasts in the larval CNS of Dps mutants [9].

Associations of Fur1 with chemical compounds

• The enzyme furin, which is encoded by the fur gene, was the first and can be considered the prototype of a mammalian subclass of subtilisin-like serine proteases [10].
• Peptidyl AMC substrates for furin, prohormone convertase and tryptase provided evidence for trypsin-like serine endopeptidases in addition to the metalloendopeptidases [11].

Other interactions of Fur1

• For the PC2, Fur1, and PAL2 enzymes, and for the dDA1 receptor, this neuronal pattern represents the vast majority of their total expression in the VNC [12].
• Nucleotide sequence analysis indicated that these cDNA clones originated from two different genes, which were called Dfur1 and Dfur2 [6].

Analytical, diagnostic and therapeutic context of Fur1

• Northern blot analysis revealed Dfur1 transcripts of 7.6, 6.5, 4.5 and 4.0 kb [3].
• These various isoforms of furin in Drosophila were characterized in gene transfer studies using immunoprecipitation analysis [3].
• 3. The characterized cDNA PCR product showed the highest degree of residue identity with the furin-related group of proteins (human/mouse furin 71%; Drosophila furin 63%) [13].

References