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Gene Review

NRP1  -  neuropilin 1

Homo sapiens

Synonyms: BDCA4, CD304, NP1, NRP, Neuropilin-1, ...
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Disease relevance of NRP1


High impact information on NRP1


Chemical compound and disease context of NRP1


Biological context of NRP1

  • Glycosylation increased VEGF binding in both cell types, but the differential GAG composition of NRP1 mediates opposite responsiveness to VEGF in ECs and SMCs [1].
  • Down-regulation of NRP1 by NRSF overexpression reduced Sema3A activity [13].
  • Using NRP1 promoter constructs in HaCaT cells, a keratinocyte cell line, we could demonstrate that a neuron restrictive silencer element (NRSE) was implicated in transcriptional repression of the NRP1 gene [13].
  • The NRP1 and NRP2 genes span over 120 and 112 kb, respectively, and are composed of 17 exons [14].
  • With the use of this rate, our model gives predictions in good quantitative agreement with several independent in vitro experiments involving VEGF(121) and VEGF(165) isoforms, confirming that VEGFR2-NRP1 coupling through VEGF(165) can fully explain the observed differences in receptor binding and phosphorylation in response to these isoforms [15].

Anatomical context of NRP1

  • It was concluded that NRSF is a transcription factor that silences NRP1 expression and thereby diminishes the Sema3A mediated inhibition of HaCaT keratinocyte migration [13].
  • The functions of NRP1 and NRP2 have been extensively studied in neurons where they act in axon guidance and in endothelial cells where they promote angiogenesis and cell migration [16].
  • During avian blood vessel development NRP1 is expressed only in arteries whereas NRP2 is expressed in veins [17].
  • Overexpression of NRP1 results in the formation of excess capillaries and hemorrhaging [17].
  • NRP1(Delta exon16) is expressed in endothelial cells, astrocytes, and various tumor cell lines, and accounts for 30% of the total NRP1 transcript [18].

Associations of NRP1 with chemical compounds

  • Here we show that a substantial fraction of NRP1 is proteoglycan modified with either heparan sulfate or chondroitin sulfate on a single conserved Ser [1].
  • Furthermore, the histone deacetylase inhibitor trichostatin A, an inhibitor of NRSF silencing activity, also increased NRP1 levels [13].
  • The affinity of VEGF165 for the NP-1 ECD was greatly enhanced either by increasing the density of immobilized NP-1 (K(d) = 113 nm) or by the addition of heparin (K(d) = 25 nm) [19].
  • The selected peptide, ATWLPPR, inhibited the VEGF(165) binding to NRP-1 but not to tyrosine kinase receptors, VEGFR-1 (flt-1) and KDR; nor did it bind to heparin [20].
  • Here we report the identification of a new NP1 transcript (designated NRP1(Delta exon16)) that contains an arginine codon in place of exon 16-derived sequences at a locus between the c-domain and membrane spanning domain [18].

Physical interactions of NRP1


Regulatory relationships of NRP1


Other interactions of NRP1


Analytical, diagnostic and therapeutic context of NRP1

  • Double in situ hybridization reveals that six-somite embryos contain intermingled extraembryonic blood island (BI) subpopulations that express np1 or np2 as well as a BI subpopulation that coexpresses both neuropilins [34].
  • RT-PCR demonstrated significantly greater expression of neuropilin-1 in normal vein compared with arterialized vein (P <0.05) [35].
  • Expression of VEGF and NP-1 in OFPAE cells and fetal placentas was confirmed by Northern and Western blot analyses [36].
  • NRP protein expression was detected by immunocytochemistry and Western blotting [37].
  • Although gene-targeting studies documenting embryonic lethality in NRP-1 null mice have demonstrated a critical role for NRP-1 in vascular development, the activities of NRP-1 in mature endothelial cells have been incompletely defined [38].


  1. Glycosaminoglycan modification of neuropilin-1 modulates VEGFR2 signaling. Shintani, Y., Takashima, S., Asano, Y., Kato, H., Liao, Y., Yamazaki, S., Tsukamoto, O., Seguchi, O., Yamamoto, H., Fukushima, T., Sugahara, K., Kitakaze, M., Hori, M. EMBO J. (2006) [Pubmed]
  2. Neuropilins in neoplasms: expression, regulation, and function. Bielenberg, D.R., Pettaway, C.A., Takashima, S., Klagsbrun, M. Exp. Cell Res. (2006) [Pubmed]
  3. Overexpression of the neuropilin 1 (NRP1) gene correlated with poor prognosis in human glioma. Osada, H., Tokunaga, T., Nishi, M., Hatanaka, H., Abe, Y., Tsugu, A., Kijima, H., Yamazaki, H., Ueyama, Y., Nakamura, M. Anticancer Res. (2004) [Pubmed]
  4. Vascular endothelial growth factor (VEGF)-like protein from orf virus NZ2 binds to VEGFR2 and neuropilin-1. Wise, L.M., Veikkola, T., Mercer, A.A., Savory, L.J., Fleming, S.B., Caesar, C., Vitali, A., Makinen, T., Alitalo, K., Stacker, S.A. Proc. Natl. Acad. Sci. U.S.A. (1999) [Pubmed]
  5. Neuropilin-2 is a receptor for the vascular endothelial growth factor (VEGF) forms VEGF-145 and VEGF-165 [corrected]. Gluzman-Poltorak, Z., Cohen, T., Herzog, Y., Neufeld, G. J. Biol. Chem. (2000) [Pubmed]
  6. Targeting neuropilin 1 as an antitumor strategy in lung cancer. Hong, T.M., Chen, Y.L., Wu, Y.Y., Yuan, A., Chao, Y.C., Chung, Y.C., Wu, M.H., Yang, S.C., Pan, S.H., Shih, J.Y., Chan, W.K., Yang, P.C. Clin. Cancer Res. (2007) [Pubmed]
  7. Deletion of the hypoxia-response element in the vascular endothelial growth factor promoter causes motor neuron degeneration. Oosthuyse, B., Moons, L., Storkebaum, E., Beck, H., Nuyens, D., Brusselmans, K., Van Dorpe, J., Hellings, P., Gorselink, M., Heymans, S., Theilmeier, G., Dewerchin, M., Laudenbach, V., Vermylen, P., Raat, H., Acker, T., Vleminckx, V., Van Den Bosch, L., Cashman, N., Fujisawa, H., Drost, M.R., Sciot, R., Bruyninckx, F., Hicklin, D.J., Ince, C., Gressens, P., Lupu, F., Plate, K.H., Robberecht, W., Herbert, J.M., Collen, D., Carmeliet, P. Nat. Genet. (2001) [Pubmed]
  8. Plexin-neuropilin-1 complexes form functional semaphorin-3A receptors. Takahashi, T., Fournier, A., Nakamura, F., Wang, L.H., Murakami, Y., Kalb, R.G., Fujisawa, H., Strittmatter, S.M. Cell (1999) [Pubmed]
  9. Neuropilin-1 is expressed by endothelial and tumor cells as an isoform-specific receptor for vascular endothelial growth factor. Soker, S., Takashima, S., Miao, H.Q., Neufeld, G., Klagsbrun, M. Cell (1998) [Pubmed]
  10. Biopanning and rapid analysis of selective interactive ligands. Giordano, R.J., Cardó-Vila, M., Lahdenranta, J., Pasqualini, R., Arap, W. Nat. Med. (2001) [Pubmed]
  11. Overexpression of neuropilin-1 promotes constitutive MAPK signalling and chemoresistance in pancreatic cancer cells. Wey, J.S., Gray, M.J., Fan, F., Belcheva, A., McCarty, M.F., Stoeltzing, O., Somcio, R., Liu, W., Evans, D.B., Klagsbrun, M., Gallick, G.E., Ellis, L.M. Br. J. Cancer (2005) [Pubmed]
  12. Overexpression of vascular endothelial growth factor164 and its co-receptor neuropilin-1 in estrogen-induced rat pituitary tumors and GH3 rat pituitary tumor cells. Banerjee, S.K., Zoubine, M.N., Tran, T.M., Weston, A.P., Campbell, D.R. Int. J. Oncol. (2000) [Pubmed]
  13. Neuron restrictive silencer factor NRSF/REST is a transcriptional repressor of neuropilin-1 and diminishes the ability of semaphorin 3A to inhibit keratinocyte migration. Kurschat, P., Bielenberg, D., Rossignol-Tallandier, M., Stahl, A., Klagsbrun, M. J. Biol. Chem. (2006) [Pubmed]
  14. Genomic organization of human neuropilin-1 and neuropilin-2 genes: identification and distribution of splice variants and soluble isoforms. Rossignol, M., Gagnon, M.L., Klagsbrun, M. Genomics (2000) [Pubmed]
  15. Differential binding of VEGF isoforms to VEGF receptor 2 in the presence of neuropilin-1: a computational model. Mac Gabhann, F., Popel, A.S. Am. J. Physiol. Heart Circ. Physiol. (2005) [Pubmed]
  16. Neuropilin-1 in the immune system. Romeo, P.H., Lemarchandel, V., Tordjman, R. Adv. Exp. Med. Biol. (2002) [Pubmed]
  17. The role of neuropilin in vascular and tumor biology. Klagsbrun, M., Takashima, S., Mamluk, R. Adv. Exp. Med. Biol. (2002) [Pubmed]
  18. Characterization of a new alternatively spliced neuropilin-1 isoform. Tao, Q., Spring, S.C., Terman, B.I. Angiogenesis (2003) [Pubmed]
  19. The interaction of neuropilin-1 with vascular endothelial growth factor and its receptor flt-1. Fuh, G., Garcia, K.C., de Vos, A.M. J. Biol. Chem. (2000) [Pubmed]
  20. Antiangiogenic and antitumor activities of peptide inhibiting the vascular endothelial growth factor binding to neuropilin-1. Starzec, A., Vassy, R., Martin, A., Lecouvey, M., Di Benedetto, M., Cr??pin, M., Perret, G.Y. Life Sci. (2006) [Pubmed]
  21. Targeting neuropilin-1 to inhibit VEGF signaling in cancer: comparison of therapeutic approaches. Mac Gabhann, F., Popel, A.S. PLoS Comput. Biol. (2006) [Pubmed]
  22. Semaphorin SEMA3F has a repulsing activity on breast cancer cells and inhibits E-cadherin-mediated cell adhesion. Nasarre, P., Kusy, S., Constantin, B., Castellani, V., Drabkin, H.A., Bagnard, D., Roche, J. Neoplasia (2005) [Pubmed]
  23. Differential binding of vascular endothelial growth factor B splice and proteolytic isoforms to neuropilin-1. Makinen, T., Olofsson, B., Karpanen, T., Hellman, U., Soker, S., Klagsbrun, M., Eriksson, U., Alitalo, K. J. Biol. Chem. (1999) [Pubmed]
  24. Neuropilin-1 binds vascular endothelial growth factor 165, placenta growth factor-2, and heparin via its b1b2 domain. Mamluk, R., Gechtman, Z., Kutcher, M.E., Gasiunas, N., Gallagher, J., Klagsbrun, M. J. Biol. Chem. (2002) [Pubmed]
  25. Myelin-, reactive glia-, and scar-derived CNS axon growth inhibitors: expression, receptor signaling, and correlation with axon regeneration. Sandvig, A., Berry, M., Barrett, L.B., Butt, A., Logan, A. Glia (2004) [Pubmed]
  26. Competing autocrine pathways involving alternative neuropilin-1 ligands regulate chemotaxis of carcinoma cells. Bachelder, R.E., Lipscomb, E.A., Lin, X., Wendt, M.A., Chadborn, N.H., Eickholt, B.J., Mercurio, A.M. Cancer Res. (2003) [Pubmed]
  27. VEGF165 mediates formation of complexes containing VEGFR-2 and neuropilin-1 that enhance VEGF165-receptor binding. Soker, S., Miao, H.Q., Nomi, M., Takashima, S., Klagsbrun, M. J. Cell. Biochem. (2002) [Pubmed]
  28. Effect of cyclophilin A on gene expression in human pancreatic cancer cells. Li, M., Wang, H., Li, F., Fisher, W.E., Chen, C., Yao, Q. Am. J. Surg. (2005) [Pubmed]
  29. Expression and regulation of the novel vascular endothelial growth factor receptor neuropilin-1 by epidermal growth factor in human pancreatic carcinoma. Parikh, A.A., Liu, W.B., Fan, F., Stoeltzing, O., Reinmuth, N., Bruns, C.J., Bucana, C.D., Evans, D.B., Ellis, L.M. Cancer (2003) [Pubmed]
  30. Neuropilin-2 is a receptor for semaphorin IV: insight into the structural basis of receptor function and specificity. Giger, R.J., Urquhart, E.R., Gillespie, S.K., Levengood, D.V., Ginty, D.D., Kolodkin, A.L. Neuron (1998) [Pubmed]
  31. Localization of vascular endothelial growth factor (VEGF) receptors in normal and adenomatous pituitaries: detection of a non-endothelial function of VEGF in pituitary tumours. Onofri, C., Theodoropoulou, M., Losa, M., Uhl, E., Lange, M., Arzt, E., Stalla, G.K., Renner, U. J. Endocrinol. (2006) [Pubmed]
  32. Induction of neuropilin-1 and vascular endothelial growth factor by epidermal growth factor in human gastric cancer cells. Akagi, M., Kawaguchi, M., Liu, W., McCarty, M.F., Takeda, A., Fan, F., Stoeltzing, O., Parikh, A.A., Jung, Y.D., Bucana, C.D., Mansfield, P.F., Hicklin, D.J., Ellis, L.M. Br. J. Cancer (2003) [Pubmed]
  33. Metabolic stress induces the lysosomal degradation of neuropilin-1 but not neuropilin-2. Bae, D., Lu, S., Taglienti, C.A., Mercurio, A.M. J. Biol. Chem. (2008) [Pubmed]
  34. Segregation of arterial and venous markers in subpopulations of blood islands before vessel formation. Herzog, Y., Guttmann-Raviv, N., Neufeld, G. Dev. Dyn. (2005) [Pubmed]
  35. Altered expression of vascular endothelial growth factor and its receptors in normal saphenous vein and in arterialized and stenotic vein grafts. Woodside, K.J., Naoum, J.J., Torry, R.J., Xue, X.Y., Burke, A.S., Levine, L., Daller, J.A., Hunter, G.C. Am. J. Surg. (2003) [Pubmed]
  36. Co-expression of vascular endothelial growth factor and neuropilin-1 in ovine feto-placental artery endothelial cells. Tsoi, S.C., Wen, Y., Chung, J.Y., Chen, D., Magness, R.R., Zheng, J. Mol. Cell. Endocrinol. (2002) [Pubmed]
  37. Selective upregulation of vascular endothelial growth factor receptors neuropilin-1 and -2 in human neuroblastoma. Fakhari, M., Pullirsch, D., Abraham, D., Paya, K., Hofbauer, R., Holzfeind, P., Hofmann, M., Aharinejad, S. Cancer (2002) [Pubmed]
  38. Neuropilin-1 regulates attachment in human endothelial cells independently of vascular endothelial growth factor receptor-2. Murga, M., Fernandez-Capetillo, O., Tosato, G. Blood (2005) [Pubmed]
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