Zurück zu Ihrem Suchergebnis

Beschreibung

Neuropilin-1 (UniProt: O14786, also known as Vascular endothelial cell growth factor 165 receptor, CD304) is encoded by the NRP1 (also known as NRP, VEGF165R) gene (Gene ID: 8829) in human. Neuropilins are highly conserved, non-tyrosine kinase, single-transmembrane glycoproteins that serve as co-receptors for various molecules, including semaphorins and vascular endothelial growth factors (VEGF). Neuropilin-1 is a single-pass type I, homodimeric, membrane glycoprotein that is synthesized with a signal peptide (aa 1-21), which is subsequently cleaved off to generate the mature form that contains a long extracellular domain (aa 22-856), a transmembrane domain (aa 857-879), and a cytoplasmic domain (aa 880-923). It acts as a receptor involved in the development of the cardiovascular system, angiogenesis, and formation of certain neuronal circuits. It is also reported to mediate the chemorepulsant activity of semaphorins. Neuropilin-1 has four well conserved domains: CUB (a1/a2, aa 27-141 and 147-265) domain, F5/8 (b1/b2, aa 275-424 and 431-583) domain, MAM domain (aa 645-811), and another domain that contains a transmembrane and a short cytoplasmic region. CUB domains mediate binding to semaphorins, while the tandem F5/8 domains are responsible for VEGF and heparin binding and recognizes a C-end role (CendR) motif R/KXXR/K on its ligands. The presence of the CUB (a1a2) domain is reported to enhance VEGF165 binding to F5/8 (b1b2) domain. The MAM domain is reported to mediate semaphorin signaling to Plexin-A. Neuropilin-1 has been recognized as an additional cellular mediator that facilitates the entry of SARS-CoV-2 into host cells. It binds to furin-cleaved spike protein and significantly potentiates SARS-CoV-2 infectivity. This effect can be blocked by monoclonal antibodies against the extracellular F5/8 (b1/b2) domain of Neuropilin-1 or with selective Neuropilin antagonists that bind to CendR binding b1 pocket. (Ref.: Kyrou, I., et al. (2021). Signal Trans. Targeted Ther. 6, Article number: 21, Daly, JL., et al. (2020). Science. 370(6518), 861-865, Cantuti-Castelvetri, L., et al. (2020). Science. 370(6518), 856-860, Mamluk, R., et al. (2002). J. Biol. Chem. 277(27), 24818-24825).