Ask about this productRelated genes to: FURIN antibody
- Gene:
- FURIN NIH gene
- Name:
- furin, paired basic amino acid cleaving enzyme
- Previous symbol:
- PCSK3, FUR, PACE
- Synonyms:
- SPC1
- Chromosome:
- 15q26.1
- Locus Type:
- gene with protein product
- Date approved:
- 1991-08-08
- Date modifiied:
- 2016-02-22
Related products to: FURIN antibody
Related articles to: FURIN antibody
- Fibrillins constitute a class of extracellular matrix proteins, and the C-terminal peptide of vertebrate fibrillin members has been identified as a hormone that regulates glucose metabolism. Their evolutionary history has attracted increasing attention recently as the hormonal roles seemingly originated in invertebrates. However, the evolution of fibrillin homologs in invertebrates such as insects, remains poorly understood. In this study, 373 annotated fibrillin sequences (including fibrillin-1, fibrillin-2, and fibrillin-3) from 181 species, 126 genera, 65 families, and 12 insect orders were retrieved and analyzed. Multidimensional analysis of phylogenesis, sequence features, conserved motifs, functional domains, and three-dimensional structures was performed on these sequences to elucidate their evolutionary relationships. Phylogenetic analysis categorized all annotated insects fibrillin sequences into three distinct clades. Among them, only the fibrillin-2 annotated members exhibit clear homology to the vertebrate fibrillin family, having diverged early from a putative ancestral protein together with the other two fibrillin annotated groups. Analysis of cysteine ratio, motif, domain composition, and furin cleavage site also revealed that only insect fibrillin-2 annotated homologs share highly similar sequence and structural features with vertebrate fibrillins. By contrast, the other two insect fibrillin annotated members are more divergent from the canonical fibrillin. Combined analyses of sequence conservation, phylogeny, domain analysis, and three-dimensional structural comparisons demonstrates that insect annotated fibrillin-1 proteins are more closely related to vertebrate fibulin than to canonical fibrillins, whereas insect annotated fibrillin-3 proteins may represent an uncharacterized insect-specific protein family associated with cell adhesion. These two groups are closely related to proteins of fibrillin family and have been misannotated in public database. - Source: PubMed
Publication date: 2026/08/24
Chen JianiZhou FengSun XinyuLi ZhuanxiaSun ShuningZhang YuyingWan Lixia - Recombinant immunotoxins (RITs) are fusion proteins of a targeting domain, such as an antibody fragment, and a truncated toxin, including exotoxin A (PE) or diphtheria toxin (DT). Limiting their possible fusion partners, the targeting domain of DT is typically fused C-terminally and that of PE is fused N-terminally. Among other factors, the activity of immunotoxins depends on the target antigen and the target-specific intracellular trafficking. Because a novel anti-CD138-PE immunotoxin was inactive against multiple myeloma, we hypothesized that rational toxin design would improve trafficking and, thus, cytotoxicity. - Source: PubMed
Publication date: 2026/08/14
Fischer ClaudiaWendland KerstinAmmon AnnaGsottberger FranziskaMellenthin LisaPetkovic SrdjanMackensen AndreasMüller Fabian - Infectious diseases typically involve a single pathogen harming its host. However, in clinical settings, co-infections also occur. This study investigated the potential interaction between Cryptococcus (C.) neoformans and influenza virus by assessing whether the cryptococcal yeast kexin protease (Kex2p) could activate the uncleaved hemagglutinin glycoprotein. Protein-protein docking was performed using HADDOCK and independently validated using AlphaFold3. 6x His-tagged truncated KEX2 gene was expressed in E. coli BL 21 (DE3), and the recombinant protein was purified using nickel ion affinity chromatography. Successful protein production was confirmed by sodium dodecyl sulfate (SDS)-polyacrylamide gel electrophoresis, anti-His immunoblotting, and mass spectrometry. Recombinant Kex2p was evaluated in a biochemical peptide cleavage assay using a fluorogenic 12-mer peptide mimicking the hemagglutinin HA1/HA2 site as substrate, with furin serving as the reference protease. HADDOCK predicted favorable binding of Kex2p to hemagglutinin (HADDOCK score = -119.2 ± 8.7; RMSD = 1.1 ± 0.2 Å), comparable to the furin-hemagglutinin complex (HADDOCK score = -115.9 ± 5.7; RMSD = 2.1 ± 1.3 Å). AlphaFold 3 independently reproduced the HADDOCK-predicted binding orientations, yielding moderate-confidence complexes for hemagglutinin-furin (ipTM = 0.50, pTM = 0.56; RMSD = 3.634 Å) and hemagglutinin-Kex2p (ipTM = 0.41, pTM = 0.58; RMSD = 3.243 Å). In enzymatic assays, recombinant Kex2p exhibited a significantly higher Vmax than furin (p = 0.0411), indicating greater catalytic activity toward the hemagglutinin cleavage peptide. These findings provide the first biochemical and complementary computational evidence that C. neoformans Kex2p may recognize influenza hemagglutinin, supporting its potential role in hemagglutinin activation during cryptococcal-influenza co-infection. - Source: PubMed
Ntshangase Nolwazi FMdana KhweziMjokane NozethuZyl Winschau F vanAlbertyn JacobusSebolai Olihile M - Matrix metalloproteinase (Mmp) dysfunction has been implicated as a driver of cartilage and neuromuscular pathologies in a common congenital disorder of glycosylation, PMM2-CDG. Since Mmp activity and interactions can be regulated by their glycans, these abnormalities were thought to likely arise from direct effects on enzyme glycosylation. However, here we show that disruptions in secretory pathway morphology alter the trafficking of Mmp2 and its activator, membrane-type Mmp MT1-Mmp. Biochemical and visual studies indicate enhanced processing by a furin proconvertase causes MT1-Mmp to directly exit the ER, bypassing the Golgi. This unconventional route of cell surface transport prevents MT1-Mmp and Mmp2 from interacting inside chondrocytes, causing pro-Mmp2 to accumulate in the Golgi. Importantly, defects in Mmp trafficking do not appear to correspond to direct defects in the N-glycosylation of either enzyme, suggesting that stress-induced alterations in secretory pathway organization may instead underlie the atypical Mmp trafficking in PMM2-CDG. - Source: PubMed
Publication date: 2026/08/10
Wu Chia-LunWiggins KaliDukes-Rimsky LynnGarapati KishorePandey AkhileshSteet RichardFlanagan-Steet Heather - The eukaryotic pathogen causes disfiguring cutaneous lesions, whose resolution can be complicated by secondary bacterial infections. Bacteria, including spp., also interact with promastigotes in the sandfly midgut. The mechanisms by which competes with bacteria and resists their toxins are poorly defined. Prior work proposed that resists the -produced pore-forming toxin aerolysin using an altered GPI-anchor. However, we found that is sensitive to aerolysin. Here, we determined the mechanism by which promastigotes are sensitive to aerolysin, using flow cytometry and biochemical approaches to analyze promastigotes genetically deficient in enzymes that produce key membrane components. The virulence factor lipophosphoglycan protected from aerolysin cytotoxicity. The metalloproteinase GP63 exerted the necessary furin-like protease activity to activate aerolysin. Leishmanial GPI-anchored proteins were necessary for aerolysin heptamerization and killing of promastigotes. Finally, mutation of the GPI-anchor binding domain of aerolysin crippled its cytotoxicity, consistent with its reliance on the GPI-anchor binding site to engage GPI anchors on the surface of promastigotes. Taken together, we propose the virulence factor lipophosphoglycan defends against pore-forming toxins made by bacterial competitors, while the GP63 metalloproteinase activates pro-aerolysin like furin. Overall, this study highlights approaches microbes use to compete with each other. - Source: PubMed
Publication date: 2026/07/30
Haram Chaitanya SSalinas SebastianSheikh Salma WaheedZhang KaiKeyel Peter A