neuropilin 1

target has curated data in GtoImmuPdb

Target id: 2998

Nomenclature: neuropilin 1

Annotation status: 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

Previous and Unofficial Names

Npn-1 | CD304 | NRP | VEGF165R

Database Links
ChEMBL Target	CHEMBL5174 (Hs), CHEMBL3309098 (Rn)
Ensembl Gene	ENSG00000099250 (Hs), ENSMUSG00000025810 (Mm), ENSRNOG00000010744 (Rn)
Entrez Gene	8829 (Hs), 18186 (Mm), 246331 (Rn)
Human Protein Atlas	ENSG00000099250 (Hs)
KEGG Gene	hsa:8829 (Hs), mmu:18186 (Mm), rno:246331 (Rn)
OMIM	602069 (Hs)
RefSeq Nucleotide	NM_003873 (Hs), NM_008737 (Mm), NM_145098 (Rn)
RefSeq Protein	NP_003864 (Hs), NP_032763 (Mm), NP_659566 (Rn)
UniProtKB	O14786 (Hs), P97333 (Mm), Q9QWJ9 (Rn)
Wikipedia	NRP1 (Hs)

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

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Ligand		Sp.	Action	Value	Parameter	Reference
EG01377		Hs	Antagonist	5.9	pK_d	4
⤷	pK_d 5.9 (K_d 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.

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 T_reg 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].

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 24/02/2020. IUPHAR/BPS Guide to PHARMACOLOGY, http://www.guidetopharmacology.org/GRAC/ObjectDisplayForward?objectId=2998.

neuropilin 1

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