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Generalities

Protein : Neuropilin-1
Gene : NRP1
Organism : Homo sapiens (Human)

Neuropilin is a transmembrane protein which has been highly conserved through evolution. Two different types of Neuropilin have been discovered in vertebrates: Neuropilin-1 (NRP1) and Neuropilin-2 (NRP2). They have 44% of similarity by comparing their amino acid sequences. In the human genome, it is located on the chromosome 10 and their molar weights fluctuate between 120 and 130 kDa. These proteins are particularly found in the membrane of the endothelial cells but the Neuropilin-1 is involved in several process such as axon guidance during the embryonic development, recognition of the Vascular Endothelial cell Growth Factor (VEGF) and recognition of covid-19.

Structural highlights

Neuropilin-1 has three different domains. A cytoplasmic domain which contains 40 residues, a transmembrane domain which contains 24 residues and a 850-residues ectodomain. The latter is an assembly of five individual motifs (a1,a2,b1,b2 and c). It contains, hence two CUB domains (a1/a2), two homologous domains to coagulation factors V/VIII (b1/b2) and a MAM domain (c). The ligand binding is mediated by the (a1/a2) and (b1/b2) portion of the ectodomain while the c domain mediates Neuripilin oligomerization.

The semaphorins (SEMA) bind to the (a1/a2/b1) domains while Vascular endothelial growth factors (VEGFs) bind to (b1/b2). The c domain as well as the transmembrane domain, are involved in the receptor dimerization.

Function

Neuropilins are involved in many signaling pathways. They act mainly as co-receptors because of their small cytoplasmic domain, and therefore associate with other receptors to transduce their signals through a cell membrane. Neuropilin-1 is involved in the development of the cardiovascular system, but also in angiogenesis (growth of new blood vessels from pre-existing ones) and organogenesis. It is also involved in the development of some neuronal circuits.

In cardiovascular development

In neuronal development

Disease

Relevance

Role in covid contamination

Applications