neuropilin 1 | Neuropilins and Plexins | IUPHAR Guide to IMMUNOPHARMACOLOGY

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neuropilin 1

  Target has curated data in GtoImmuPdb

Target id: 2998

Nomenclature: neuropilin 1

Family: Neuropilins and Plexins

Annotation status:  image of a grey circle Awaiting annotation/under development. Please contact us if you can help with annotation.  » Email us

Gene and Protein Information
Species TM AA Chromosomal Location Gene Symbol Gene Name Reference
Human 1 923 10p11.22 NRP1 neuropilin 1
Mouse 1 923 8 E2; 8 75.78 cM Nrp1 neuropilin 1
Rat 1 922 19q12 Nrp1 neuropilin 1
Gene and Protein Information Comments
Several alternatively spliced transcript variants that encode different protein isoforms originating from the human and mouse genes have been identified.
Previous and Unofficial Names
Npn-1 | CD304 | NRP | VEGF165R
Database Links
ChEMBL Target
Ensembl Gene
Entrez Gene
Human Protein Atlas
KEGG Gene
OMIM
RefSeq Nucleotide
RefSeq Protein
UniProtKB
Wikipedia
Selected 3D Structures
Image of receptor 3D structure from RCSB PDB
Description:  Neuropilin1-b1 domain in complex with EG01377.
PDB Id:  6FMC
Ligand:  EG01377
Resolution:  0.9Å
Species:  Human
References:  4
Natural/Endogenous Ligands
semaphorin 3A {Sp: Human}

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Antagonists
Key to terms and symbols View all chemical structures Click column headers to sort
Ligand Sp. Action Value Parameter Reference
EG01377 Hs Antagonist 5.9 pKd 4
pKd 5.9 (Kd 1.32x10-6 M) [4]
Description: Evaluated using a SPR binding assay (Biacore), measuring competitive displacement of biotinylated VEGF from immobilised recombinant NRP1 b1b2 protein.
EG01377 Hs Antagonist 6.2 pIC50 4
pIC50 6.2 (IC50 6.09x10-7 M) [4]
Description: In a cell free assay.
Immunopharmacology Comments
NRP1 is expressed on several types of immune cells (e.g. T cells, dendritic cells) [5-6], and it is involved in potentiating the function and survival of regulatory T cells (Tregs) [1]. In the tumour microenvironment NRP1-mediated regulation of Tregs acts as a barrier to effective anti-tumour immunity. Subsequently, pharmacological inhibition of NRP1 function is being examined via the development of selective antagonists that are predicted to offer anti-angiogenic, anti-tumour and immunomodulatory activities that may be applicable in immuno-oncology [4]. It is hoped that targeting NRP1 will limit Treg-mediated tumour-induced tolerance without inducing autoimmunity.
Cell Type Associations
Immuno Cell Type:  T cells
Cell Ontology Term:   regulatory T cell (CL:0000815)
Comment:  Neuropilin 1 is expressed by Treg cells and promotes their function and survival.
References:  1
Immuno Cell Type:  Dendritic cells
References:  5-6
General Comments
Neuropilin 1 is a type I transmembrane protein that is a co-receptor for a number of different growth factors (TGFβ1, PLGF, HGF and class 3 secreted semaphorin ligands), which plays crucial roles in vascular and neuronal development. The semaphorins were originally identified for their roles in repulsive axon guidance during development of the central and peripheral nervous systems [2]. Neuropilin 1 is also a receptor for the mitogenic, heparin-binding form or VEGF, VEGF165, on endothelial and tumour cells. VEGF165 competes with semaphorin 3A for neuropilin 1 binding sites on endothelial cells [3].

References

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1. Delgoffe GM, Woo SR, Turnis ME, Gravano DM, Guy C, Overacre AE, Bettini ML, Vogel P, Finkelstein D, Bonnevier J et al.. (2013) Stability and function of regulatory T cells is maintained by a neuropilin-1-semaphorin-4a axis. Nature, 501 (7466): 252-6. [PMID:23913274]

2. Kolodkin AL, Matthes DJ, Goodman CS. (1993) The semaphorin genes encode a family of transmembrane and secreted growth cone guidance molecules. Cell, 75 (7): 1389-99. [PMID:8269517]

3. Narazaki M, Tosato G. (2006) Ligand-induced internalization selects use of common receptor neuropilin-1 by VEGF165 and semaphorin3A. Blood, 107 (10): 3892-901. [PMID:16424390]

4. Powell J, Mota F, Steadman D, Soudy C, Miyauchi JT, Crosby S, Jarvis A, Reisinger T, Winfield N, Evans G et al.. (2018) Small Molecule Neuropilin-1 Antagonists Combine Antiangiogenic and Antitumor Activity with Immune Modulation through Reduction of Transforming Growth Factor Beta (TGFβ) Production in Regulatory T-Cells. J. Med. Chem., 61 (9): 4135-4154. [PMID:29648813]

5. Roy S, Bag AK, Singh RK, Talmadge JE, Batra SK, Datta K. (2017) Multifaceted Role of Neuropilins in the Immune System: Potential Targets for Immunotherapy. Front Immunol, 8: 1228. [PMID:29067024]

6. Tordjman R, Lepelletier Y, Lemarchandel V, Cambot M, Gaulard P, Hermine O, Roméo PH. (2002) A neuronal receptor, neuropilin-1, is essential for the initiation of the primary immune response. Nat. Immunol., 3 (5): 477-82. [PMID:11953749]

How to cite this page

Neuropilins and Plexins: neuropilin 1. Last modified on 18/10/2018. Accessed on 16/09/2019. IUPHAR/BPS Guide to PHARMACOLOGY, http://www.guidetoimmunopharmacology.org/GRAC/ObjectDisplayForward?objectId=2998.