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	OMIM: 602069 MGI: 106206 HomoloGene: 2876 GeneCards: NRP1
Gene location (Human)
Chr.	Chromosome 10 (human)[1]
End	33,336,262 bp[1]
Gene location (Mouse)
Chr.	Chromosome 8 (mouse)[2]
End	128,503,363 bp[2]
RNA expression pattern
	; ; ; ;
	More reference expression data
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; • GO:0001948 protein binding; • GO:0005097, GO:0005099, GO:0005100 GTPase activator activity; • protein kinase binding;
Cellular component	• cytosol; • membrane; • extracellular region; • semaphorin receptor complex; • cell surface; • sorting endosome; • integral component of membrane; • growth cone; • receptor complex; • cell membrane; • axon; • neuronal cell body; • early endosome; • neurofilament; • cytoplasmic vesicle; • extracellular; • focal adhesion; • neuron projection; • glutamatergic synapse; • integral component of postsynaptic membrane;
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; • 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; • 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; • motor neuron migration; • outflow tract septum morphogenesis; • substrate-dependent cell migration, cell extension; • integrin-mediated signaling pathway; • positive regulation of endothelial cell migration; • actin cytoskeleton reorganization; • regulation of Cdc42 protein signal transduction; • substrate adhesion-dependent cell spreading; • neuropilin signaling pathway; • VEGF-activated neuropilin signaling pathway; • positive regulation of phosphorylation; • endothelial cell migration; • GO:0032320, GO:0032321, GO:0032855, GO:0043089, GO:0032854 positive regulation of GTPase activity; • positive regulation of angiogenesis; • positive regulation of filopodium assembly; • positive regulation of stress fiber assembly; • positive regulation of focal adhesion assembly; • positive regulation of cell migration involved in sprouting angiogenesis; • positive regulation of substrate adhesion-dependent cell spreading; • positive regulation of actin cytoskeleton reorganization; • postsynapse organization; • basal dendrite development; • basal dendrite arborization;
	Sources:Amigo / QuickGO
Orthologs
	8829
	18186
	ENSG00000099250
	ENSMUSG00000025810
	O14786
	P97333
NM_001024628; NM_001024629; NM_001244972; NM_001244973; NM_003873;
	NM_001330068
	NM_008737; NM_001358959; NM_001358960
NP_001019799; NP_001019800; NP_001231901; NP_001231902; NP_001316997;
	NP_003864
	NP_032763; NP_001345888; NP_001345889
	Wikidata
View/Edit Human	View/Edit Mouse

Neuropilin-1 is a protein that in humans is encoded by the NRP1 gene.[5][6][7] In humans, the neuropilin 1 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][7]

Interactions

Neuropilin 1 has been shown to interact with Vascular endothelial growth factor A.[5][8]

Implication in cancer

Neuropilin 1 has been implicated in the vascularization and progression of cancers. NRP1 expression has been shown to be elevated in a number of human patient tumor samples, including brain, prostate, breast, colon, and lung cancers and NRP1 levels are positively correlated with metastasis.[9][10][11][12][13][14]

In prostate cancer NRP1 has been demonstrated to be an androgen-suppressed gene, upregulated during the adaptive response of prostate tumors to androgen-targeted therapies and a prognostic biomarker of clinical metastasis and lethal PCa.[9] In vitro and in vivo mouse studies have shown membrane bound NRP1 to be proangiogenic and that NRP1 promotes the vascularization of prostate tumors.[15]

Elevated NRP1 expression is also correlated with the invasiveness of non-small cell lung cancer both in vitro and in vivo.[14]

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.[16] EG3287 has been shown to induce apoptosis in tumor cells with elevated NRP1 expression.[16] A patent for EG3287 was filed in 2002 and approved in 2003.[17] As of 2015 there were no clinical trials ongoing or completed for EG3287 as a human cancer therapy.

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.[18]

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