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Description

Neuropilin-2 (UniProt: O60462, also known as Vascular endothelial cell growth factor 165 receptor 2) is encoded by the NRP2 (also known as VEGF165R2) gene (Gene ID: 8828) in human. Neuropilin-2 is a single-pass type I membrane protein that serves as a high affinity receptor for VEGF165 and VEGF145, semaphorins 3C, 3F, and the PLGF-2 isoform of PGF. It is synthesized with a signal peptide (aa 1-20) that is subsequently cleaved in the mature form. Neuropilin-2 has an extracellular domain (aa 21-864), a transmembrane domain (aa 865-889), and cytoplasmic tail (aa 890-931). It contains two CUB domains (aa 28-142 and 149-267) that mediate its binding to semaphorin. It also has two F5/8 type -C domains that are responsible for heparin and VEGF binding. Six different isoforms of Neuropilin-2 have been described that are produced by alternative splicing. In non small cell lung cancer (NSCLC) cell lines, TGF-beta signaling is reported to preferentially increase the abundance of NRP2b. Although it has been shown that the presence of NRP2b inhibits the proliferation of cultured cells and diminishes primary tumor growth, it also enhances cellular migration, invasion into Matrigel, and tumorsphere formation in cultured cells in response to TGF-beta. In addition, it is shown to promote metastasis in xenograft murine models. In lung cancer cell lines, knocking down of NRP2 is shown to impair both baseline and TGF-beta-induced migration and invasion. (Ref.: Gemmill, RM., et al., (2017). Sci. Signal. 10, eaag0528).