• Purity

  >90%, by SDS-PAGE under reducing conditions and visualized by silver stain

• Endotoxin Level

  <0.01 EU per 1 μg of the protein by the LAL method.  

• Activity

  Measured by its binding ability in a functional ELISA. Immobilized rrNpn-1/Fc Chimera at 2 µg/mL (100 µL/well) can bind rhVEGF    ₁₆₅ in the presence of 2 µg/mL of heparin with an apparent K    _D <1 nM.  

• Source

  Mouse myeloma cell line, NS0-derived

  Rat Neuropilin-1 (Phe22 - Ala810) Accession # Q9QWJ9	R	Rat Neuropilin-1 (Ser829 - Asp854) Accession # Q9QWJ9	IEGRDMD	Human IgG1 (Pro100 - Lys330)	6-His tag
  N-terminus					C-terminus

  R&D Systems rat Npn-1 may represent a previously unreported splice isoform of rat Npn-1.    
   

• Accession #

• N-terminal Sequence    
  Analysis

  Phe22

• Structure / Form

  Disulfide-linked homodimer

• Predicted Molecular Mass

  119 kDa (monomer)

• SDS-PAGE

  130-150 kDa, reducing conditions

Background: Neuropilin-1

Neuropilin-1 (Npn-1, previously neuropilin; also named CD304) is a 130 - 140 kDa type I transmembrane (TM) glycoprotein that regulates axon guidance and angiogenesis (1 - 4). The full-length 922 amino acid (aa) rat Npn-1 contains a 623 aa extracellular domain (ECD) that shares 98% aa identity with mouse and 93% aa identity with human, equine, bovine and canine Npn-1 (3, 4). The ECD contains two N-terminal CUB domains (termed a1a2), two domains with homology to coagulation factors V and VIII (b1b2) and a MAM (meprin) domain (c). In mouse and human, splice variants that lack the TM domain have been described and are either proven or presumed to be soluble antagonists (1, 5 - 7). The sema domains of Class III secreted semaphorins such as Sema3A bind Npn-1 a1a2 (8). Heparin, the heparin-binding forms of VEGF (VEGF₁₆₅, VEGF-B and VEGF-E), PlGF (PlGF2), and the C-terminus of Sema3 bind the b1b2 region (8, 9). Npn-1 and Npn-2 share 48% aa identity within the ECD and can form homo- and hetero-oligomers via interaction of their MAM domains (1). Neuropilins show partially overlapping expression in neuronal and endothelial cells during development (1, 2). Both neuropilins act asco-receptors with plexins, mainly plexin A3 and A4, to bind class III semaphorins that mediate axon repulsion (10). However, only Npn-1 binds Sema3A, and only Npn-2 binds Sema3F (1). Both areco-receptors with VEGF R2 (also called KDR or Flk-1) for VEGF₁₆₅ binding (1). Sema3A signaling can be blocked by VEGF₁₆₅, which has higher affinity for Npn-1 (11). Npn-1 is preferentially expressed in developing or remodeling arteries (1, 2). Npn-1 is also expressed on dendritic cells and mediates DC-induced T cell proliferation (12).

• References:

1. Bielenberg, D.R. et al. (2006) Exp. Cell Res. 312:584. 

2. Gu, C. et al. (2003) Dev. Cell 5:45. 

3. He, Z. and M. Tessier-Lavigne (1997) Cell 90:739.

4. Soker, S. et al. (1998) Cell 92:735.

5. Gagnon, M.L. et al. (2000) Proc. Natl. Acad. Sci. USA 97:2573. 

6. Cackowski, F.C. et al. (2004) Genomics 84:82. 

7. Rossignol, M. et al. (2000) Genomics 70:211.

8. Gu, C. et al. (2002) J. Biol. Chem. 277:18069.

9. Mamluk, R. et al. (2002) J. Biol. Chem. 277:24818.

10. Yaron, A. et al. (2005) Neuron 45:513.

11. Narazaki, M. and G. Tosato (2006) Blood 107:3892.

12. Tordjman, R. et al. (2002) Nat. Immunol. 3477.

• Entrez Gene IDs:

  8829 (Human); 18186 (Mouse); 246331 (Rat)

• Alternate Names:

  BDCA4; BDCA-4; CD304 antigen; CD304; DKFZp686A03134; DKFZp781F1414; neuropilin 1; Neuropilin1; Neuropilin-1; NRP1; NRPNP1; transmembrane receptor; Vascular endothelial cell growth factor 165 receptor; VEGF165RCD304