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FLASH GENE
Symbol NRP1 contributors: mct/shn - updated : 03-11-2016
HGNC name neuropilin 1
HGNC id 8004
Location 10p11.22      Physical location : 33.466.419 - 33.623.833
Synonym name
  • vascular endothelial growth factor-165 receptor
  • transmembrane receptor
  • CD304 antigen
  • A5 protein
  • Neuropilin-1 precursor (A5 protein)
  • neuropilin-1
  • Synonym symbol(s) VEGF165R, NRP, NPN1, CD304, BDCA4, DKFZp686A03134, DKFZp781F1414, NP1, C530029I03, NP-1, NPN-1, Npn1, Nrp
    DNA
    TYPE functioning gene
    STRUCTURE 157.41 kb     17 Exon(s)
    10 Kb 5' upstream gene genomic sequence study
    regulatory sequence Promoter
    Binding site
    text structure promoter sequence contains an E2F1 binding site
    MAPPING cloned Y linked N status confirmed
    Map pter - D10S1243 - D10S199 - NRP1 - D10S1066 - D10S675 - cen
    RNA
    TRANSCRIPTS type messenger
    identificationnb exonstypebpproduct
    ProteinkDaAAspecific expressionYearPubmed
    17 splicing 5895 - 923 endothelial and tumor cells 1998 9529250
    also called isoform a, NRP1 or VEGF165R
    12 splicing 2478 71.78 644 soluble isoform 2000 10688880
  • binding VEGF165R
  • also called isoform b, NRP1s12
  • 17 splicing 5874 - 916 - -
    11 splicing 2373 - 609 - 2004 15203206
    also called isoform c, NRP1s4
    17 splicing 5877 - 917 - -
    14 splicing 5692 - - - -
    Non-protein coding gene or gene fragment, no protein prediction available
    EXPRESSION
    Type ubiquitous
       expressed in (based on citations)
    organ(s)
    SystemOrgan level 1Organ level 2Organ level 3Organ level 4LevelPubmedSpeciesStageRna symbol
    Cardiovascularvesselscapillary  highly
    Digestiveliver   moderately
    Endocrinepancreas   moderately
    Hearing/Equilibriumearinnercochlea highly
    Reproductivefemale systembreast  moderately
    Urinarykidney   moderately
    tissue
    SystemTissueTissue level 1Tissue level 2LevelPubmedSpeciesStageRna symbol
    Connectivebone  highly
    Epithelialsecretoryglandularendocrine 
    Muscularsmoothmyoepithelium  
    Muscularstriatumskeletal highly
    cells
    SystemCellPubmedSpeciesStageRna symbol
    Cardiovascularendothelial cell
    Lymphoid/Immunedendritic cell
    cell lineage
    cell lines tumor cell lines
    fluid/secretion
    at STAGE
    physiological period embryo, fetal, pregnancy
    Text in the developing nervous system, placenta, embryonic vessels
    PROTEIN
    PHYSICAL PROPERTIES
    STRUCTURE
    motifs/domains
  • two N terminal complement C1r/s homology domain (CUB domain), in large extracellular region (a1a2)
  • two coagulation factor V/VIII homology
  • domains (designated b1b2)
  • two regions of homology with the C1 and C2 domains of coagulation factor F5
  • a MAM (meprin, A5 antigen, receptor tyrosine phosphatase mu) domain
  • a single transmembrane segment
  • a GIPC (synectin) binding motif (deletion of the GIPC binding motif prevented transition of KDR through RAB11A vesicles and attenuated signaling)
  • a short cytoplasmic C terminal tail, with three C-terminal residues which form a PDZ-binding motif that influences NRP1-mediated angiogenesis
  • conjugated GlycoP
    mono polymer heteromer , dimer
    HOMOLOGY
    interspecies ortholog to Nrp1, Rattusnorvegicus
    ortholog to Nrp1, Mus musculus
    ortholog to NRP1, Pan troglodytes
    Homologene
    FAMILY
  • neuropilin family
  • CATEGORY receptor
    SUBCELLULAR LOCALIZATION     plasma membrane
        intracellular
    intracellular,cytoplasm,organelle,membrane
    intracellular,cytoplasm,organelle,endoplasmic reticulum
    text type I transmembrane glycoprotein
    basic FUNCTION
  • plays an important role in allowing the endothelial tip cell filopodia to switch substrate and protrude in a new direction at a specific location in the developing brain
  • implicated in repulsive axon guidance, angiogenesis, cell survival, control of neuronal migration
  • contributes to both neuronal and vascular patterning by preferentially relaying SEMA3A signals in peripheral axons and VEGF164 signals in blood vessels
  • function in signaling SEMA3A-evoked neuronal death through FER in cortical neurons
  • may be a multiple function protein in breast involved in the induction of local invasiveness of neoplasia and angiogenesis and having direct relevance to the progression of breast cancer
  • facilitates tumor growth and progression
  • labile to internalization and lysosomal degradation in response to metabolic stress
  • playing a role with CHL1 in establishment of proper targeting of specific thalamocortical projections
  • regulates vascular and neural development and acts as a co-receptor for VEGFRs and plexins
  • plays a prominent role in regulating ligand-induced PDGFR signalling
  • essential co-receptor for PDGFR signalling, which
  • may critically contribute to the formation of blood vessels and other mesenchymal tissues
  • co-receptor for members of the VEGF (vascular endothelial growth factor) family in endothelial cells
  • role for NRP1 and NRP1 glycosylation in mediating PDGF-induced VSMC migration, possibly by acting as a co-receptor for PDGFRA and via selective mobilization of a novel BCAR1 tyrosine phosphorylation pathway
  • distinct role of NRP1 in KDR signaling
  • VEGF164/NRP1 signalling promotes GnRH neuron survival cell-autonomously
  • NRP1 and NRP2 are receptors for guidance cues of the class 3 semaphorin (SEMA) family and are expressed in partially overlapping patterns in sympathetic neural crest (NC) cells and their progeny
  • is dispensable for suppression of autoimmunity and maintenance of immune homeostasis, but is required by Treg cells to limit anti-tumour immune responses and to cure established inflammatory colitis
  • functions as a receptor for SEMA4A on Treg cells, and SEMA4A–NRP1 interaction promotes Treg-cell survival and function
  • role for NRP1 in modulating Treg-cell stability, survival and function in certain tumour microenvironments
  • NRP1 and NRP2 are transmembrane glycoproteins that are essential for Neural crest cells (NCCs) migration
  • SEMA3A, -3C, and -3F, likely with coreceptors NRP1, NRP2, and plexin-A1 and/or -A3, promote migration and possibly other activities of human DCs during innate and adaptive immune responses
  • CELLULAR PROCESS
    PHYSIOLOGICAL PROCESS immunity/defense , nervous system
    text initiation of primary immune response
    PATHWAY
    metabolism
    signaling
  • critical role for a novel NRP1-BCAR1 pathway in the regulation of chemotaxis
  • a component
  • necessary constituent of receptor complexes for some but not all secreted semaphorin family members
  • complexing with plexin (PLXNB1) to form semaphorin 3* receptors
  • complexing with Sema-3A in the regulation of migration and adhesion of thymocytes
  • VAMP2 associated with Neuropilin 1 (NRP1) and PLXNA1, two essential components of the SEMA3A receptor, via its juxtatransmembrane domain
  • INTERACTION
    DNA
    RNA
    small molecule
    protein
  • plexin 1, Plex1
  • semaphorins
  • VEGF(165)
  • vascular endothelial growth factor 165, placenta growth factor-2, and heparin
  • E2F1
  • LGALS1
  • CK2 holoenzyme
  • SEMA3A
  • PDGFRA and PDGFRB
  • vascular endothelial growth factor A, VEGFA
  • NRP1 regulates a new VEGF-induced gene, PHACTR1
  • SEMA3A and NRP1 binding stimulated osteoblast and inhibited adipocyte differentiation through the canonical WNT/CTNNB1 signalling pathway
  • SEMA3A and NRP1 transduce signals through TAOK2 and JNK to regulate basal dendrite development in cortical neurons
  • motoneuronal SEMA3C regulates the shared SEMA3 neuropilin receptors NRP1 and NRP2 levels in opposite ways at the growth cone surface
  • bind SEMA3A, which shares homology with SEMA4A, and vascular endothelial growth factor (VEGFA) in mediating neural axon growth and angiogenesis
  • LGALS1 induces vascular permeability through the NRP1/FLT1 complex
  • neural crest-derived SEMA3C activates endothelial NRP1 for cardiac outflow tract septation
  • VEGFA induced interactions between NRP1 and GIPC1, a scaffold protein, and complex formation between GIPC1 and SYX, a RhoGEF (PMID/
  • PTN interacted directly with NRP1 through its thrombospondin type-I repeat domains
  • NRP1 and NRP2 are co-receptors for heparin-binding growth factors and class 3 semaphorins
  • interaction between the two unrelated guidance receptors EFNBB1 and NRP1, that is used to control the navigation of post-crossing axons in the corpus callosum
  • cell & other
    REGULATION
    Other phosphorylated by CK2
    ASSOCIATED DISORDERS
    corresponding disease(s)
    Other morbid association(s)
    TypeGene ModificationChromosome rearrangementProtein expressionProtein Function
    tumoral     --over  
    in agressive advanced prostate carcinoma and in astrocytoma cell lines,in breast cancer in progression
    constitutional   deletion    
    deletion of NRP1 in normal epidermis prevents skin tumour initiation
    Susceptibility
    Variant & Polymorphism
    Candidate gene
    Marker
    Therapy target
    ANIMAL & CELL MODELS
  • Transgenic mice, in which both NP1 and NP2 were targeted died in utero at E8.5
  • Mice deficient for NP2 but heterozygous for NP1 or deficient for NP1 but heterozygous for NP2 were also embryonic lethal and survived to E10-E10.5
  • Morpholino-mediated knockdown of zNRP1 in embryos resulted in vascular defects, most notably impaired circulation in the intersegmental vessels
  • Overexpression of Y297A and D320A NRP1 mutations in human umbilical vein endothelial cells reduced high-affinity VEGF binding and migration toward a VEGF gradient, and markedly inhibited VEGF-induced angiogenesis in a coculture cell model