VEGF-A(165) plays a central role in neovascularization. The biological activities of VEGF-A165 are largely mediated through KDR. VEGF-A 165 also binds to cellular coreceptors, neuropilin-1 (NP-1), and heparin, via its C-terminal domain, resulting in functional modulation. Parapoxvirus-encoded VEGFs (PV-VEGFs), which recognize KDR, possess basic amino acid clusters in their C-terminal regions. Some PV-VEGFs may interact with NP-1; however, the NP-1- and heparin-binding properties have not been fully characterized. Here, we demonstrate that the heparin- and NP-1-binding region of PV-VEGFs is located in its C-terminal tail. Furthermore, the two arginine residues adjacent to the C-terminus greatly contribute to both interactions. (c) 2006 Elsevier Inc. All rights reserved.