neuropilin2

Neuropilin-2 (NRP2) is a type I transmembrane glycoprotein that functions primarily as a co-receptor for certain growth factors and guidance cues. It is encoded by the NRP2 gene and participates in signaling together with other receptors, notably vascular endothelial growth factor receptors (VEGFRs) and plexins, while lacking intrinsic catalytic activity of its own. NRP2 forms receptor complexes that modulate signaling pathways involved in vascular and neural development as well as immune cell responses.

The protein has an extracellular domain composed of a1, a2, b1, and b2 subdomains, a single-pass transmembrane region, and a short cytoplasmic tail. It binds a subset of ligands, including VEGF-C and VEGF-D, which link it to lymphangiogenesis and angiogenesis, and class 3 semaphorins such as SEMA3A and SEMA3F, which connect it to axon guidance. For semaphorin signaling, NRP2 typically acts in concert with plexins to transduce signals that control cellular migration and axonal pathfinding. The cytoplasmic tail is short and interacts with PDZ domain-containing scaffolding proteins, influencing receptor trafficking and signaling strength. Alternative splicing can generate multiple isoforms with differences in the cytoplasmic region, affecting intracellular interactions.

Expression of NRP2 is observed in lymphatic and blood vascular endothelium, various neural populations, and certain immune cells. Functionally, it contributes to lymphangiogenesis, angiogenesis, neuronal wiring, and modulation of immune cell movement. In pathology, high NRP2 activity has been linked to tumor progression and metastasis through enhanced lymphatic vessel formation and altered tumor cell migration, making it a potential therapeutic target in cancer and other diseases.