Neuropilin 1

NRP1
Available structures PDB Ortholog search: PDBe RCSB List of PDB id codes 1KEX, 2QQI, 2QQM, 2QQN, 3I97, 4DEQ, 4RN5, 5C7G
Identifiers
Aliases	NRP1, BDCA4, CD304, NP1, NRP, VEGF165R, Neuropilin 1
External IDs	MGI: 106206 HomoloGene: 2876 GeneCards: NRP1
Genetically Related Diseases
tetralogy of Fallot[1]
Gene ontology Molecular function • heparin binding • vascular endothelial growth factor binding • cytokine binding • semaphorin receptor activity • coreceptor activity • metal ion binding • vascular endothelial growth factor-activated receptor activity • growth factor binding • protein binding Cellular component • cytosol • membrane • focal adhesion • extracellular region • semaphorin receptor complex • extracellular fluid • cell surface • sorting endosome • integral component of membrane • growth cone • receptor complex • plasma membrane • axon • neuronal cell body • early endosome • neurofilament • cytoplasmic vesicle Biological process • negative regulation of neuron apoptotic process • facioacoustic ganglion development • vascular endothelial growth factor signaling pathway • VEGF-activated neuropilin signaling pathway involved in axon guidance • toxin transport • cell migration involved in sprouting angiogenesis • semaphorin-plexin signaling pathway involved in axon guidance • positive regulation of retinal ganglion cell axon guidance • positive regulation of smooth muscle cell migration • sympathetic neuron projection guidance • vascular endothelial growth factor receptor signaling pathway • sensory neuron axon guidance • angiogenesis • positive regulation of ERK1 and ERK2 cascade • animal organ morphogenesis • protein localization to early endosome • trigeminal nerve structural organization • regulation of axon extension involved in axon guidance • coronary artery morphogenesis • negative regulation of extrinsic apoptotic signaling pathway • neuron development • trigeminal nerve morphogenesis • angiogenesis involved in coronary vascular morphogenesis • commissural neuron axon guidance • negative regulation of axon extension involved in axon guidance • heart development • response to wounding • artery morphogenesis • positive regulation of peptidyl-tyrosine phosphorylation • branching involved in blood vessel morphogenesis • platelet-derived growth factor receptor signaling pathway • positive chemotaxis • facial nerve structural organization • hepatocyte growth factor receptor signaling pathway • axonal fasciculation • retina vasculature morphogenesis in camera-type eye • dorsal root ganglion morphogenesis • axon extension involved in axon guidance • sympathetic ganglion development • cell differentiation • semaphorin-plexin signaling pathway involved in neuron projection guidance • cellular response to hepatocyte growth factor stimulus • dendrite development • sprouting angiogenesis • neuron migration • nervous system development • regulation of retinal ganglion cell axon guidance • branchiomotor neuron axon guidance • gonadotrophin-releasing hormone neuronal migration to the hypothalamus • negative regulation of axon extension • retinal ganglion cell axon guidance • renal artery morphogenesis • ventral trunk neural crest cell migration • VEGF-activated neuropilin signaling pathway • positive regulation of endothelial cell proliferation • sympathetic nervous system development • endothelial tip cell fate specification • cell-cell signaling • regulation of vesicle-mediated transport • trigeminal ganglion development • positive regulation of cytokine activity • positive regulation of axon extension involved in axon guidance • axon guidance • vestibulocochlear nerve structural organization • positive regulation of endothelial cell migration • multicellular organism development • neural crest cell migration involved in autonomic nervous system development • endothelial cell chemotaxis • axonogenesis involved in innervation • dichotomous subdivision of terminal units involved in salivary gland branching • cellular response to vascular endothelial growth factor stimulus • motor neuron axon guidance • nerve development • cell migration • sympathetic neuron projection extension • semaphorin-plexin signaling pathway • signal transduction • otic placode development Sources:Amigo / QuickGO
RNA expression pattern
More reference expression data
Orthologs
Species	Human	Mouse
Entrez	8829	18186
Ensembl	ENSG00000099250	ENSMUSG00000025810
UniProt	O14786	P97333
RefSeq (mRNA)	NM_001024628 NM_001024629 NM_001244972 NM_001244973 NM_003873	NM_008737
RefSeq (protein)	NP_001019799.1 NP_001019800.1 NP_003864.4	NP_032763.2
Location (UCSC)	Chr 10: 33.18 – 33.34 Mb	Chr 8: 128.36 – 128.51 Mb
PubMed search	[2]	[3]
Wikidata

Neuropilin-1 is a protein that in humans is encoded by the NRP1 gene.^[4][5][6] In humans, the neuropilin 11 gene is located at 10p11.22. This is one of two human neuropilins.

Function

NRP1 is a membrane-bound coreceptor to a tyrosine kinase receptor for both vascular endothelial growth factor (VEGF; MIM 192240) and semaphorin (see SEMA3A; MIM 603961) family members. NRP1 plays versatile roles in angiogenesis, axon guidance, cell survival, migration, and invasion.[supplied by OMIM]^[6]

Interactions

Neuropilin 1 has been shown to interact with Vascular endothelial growth factor A.^[4][7]

Implication in cancer

Neuropilin 1 has been implicated in the vascularization and progression of cancers. In vitro and in vivo mouse studies have shown membrane bound NRP1 to be proangiogenic and promotes the vascularization of prostate tumors.^[8] NRP1 expression levels have been shown to be elevated in a number of human patient tumor samples, including brain, prostate, breast, colon, and lung cancers and is associated with metastasis.^{[9][10][11][12][13]} Elevated NRP1 expression is also correlated with the invasiveness of non-small cell lung cancer both in vitro and in vivo.^[13]

Target for cancer therapies

As a co-receptor for VEGF, NRP1 is a potential target for cancer therapies. A synthetic peptide, EG3287, was generated in 2005 and has been shown to block NRP1 activity.^[14] EG3287 has been shown to induce apoptosis in tumor cells with elevated NRP1 expression.^[14] A patent for EG3287 was filed in 2002 and approved in 2003.^[15] As of 2015 there were no clinical trials ongoing or completed for EG3287 as a human cancer therapy.

Interestingly, soluble NRP1 has the opposite effect of membrane bound NRP1 and has anti-VEGF activity. In vivo mouse studies have shown that injections of sNRP-1 inhibits progression of acute myeloid leukemia in mice.^[16]

References

Further reading

PDB gallery
1kex: Crystal Structure of the b1 Domain of Human Neuropilin-1  2orx: Structural Basis for Ligand Binding and Heparin Mediated Activation of Neuropilin  2orz: Structural Basis for Ligand Binding and Heparin Mediated Activation of Neuropilin