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FLASH GENE
Symbol NRP1 contributors: mct/shn - updated : 03-11-2017
HGNC name neuropilin 1
HGNC id 8004
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
  • requirement for NRP1 and PLXNA1 in dendrite polarization occurs at a developmental time point after the cells have already extended their basally directed axon
  • 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
  • SEMA3A binds its receptors neuropilin NRP1 or NRP2 to position these axons for correct GnRH neuron migration, with an additional role for the NRP co-receptor PLXNA1
    • 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