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FLASH GENE
Symbol NRP2 contributors: mct - updated : 24-02-2017
HGNC name neuropilin 2
HGNC id 8005
PROTEIN
PHYSICAL PROPERTIES
STRUCTURE
motifs/domains
  • a 20 amino acids signal peptide (2.5 kDa)
  • two N terminal complement C1r/s homology domain (CUB domain)
  • two regions of homology with the C1 and C2 domains of coagulation factor F5
  • a MAM domain
  • a single transmembrane segment and a short cytoplasmic C terminal tail
    • conjugated GlycoP
    isoforms Precursor a 911 amino acids mature peptide (102.3 kDa)
    HOMOLOGY
    interspecies homolog to rattus Nrp2 (93.84 pc)
    homolog to murine Nrp2 (94.53 pc)
    Homologene
    FAMILY semaphorin family
    CATEGORY receptor
    SUBCELLULAR LOCALIZATION extracellular
        plasma membrane
    basic FUNCTION
  • semaphorin 3C and 3F receptor
  • implicated in repulsive axon guidance and vascular endothelial growth factor
  • can function in the absence of NRP1 to mediate endothelial tube formation in hypoxia
  • involved in the organization and fasciculation of several cranial nerves and spinal nerves
  • function as receptors for both the semaphorins and vascular endothelial growth factor
  • can function in the absence of NRP1 to mediate endothelial tube formation in hypoxia
  • important role in cancer and angiogenesis
  • cell surface receptor involved in angiogenesis and axonal guidance, has recently been shown to be a critical mediator of tumor-associated lymphangiogenesis
  • NRP2 is a mediator of prorelaxant stimuli in SMCs, suggesting a novel function for NRP2 as a regulator of visceral smooth muscle (SM) contractility
  • 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
  • role of NRP2 in the ipsilateral growth of midbrain dopaminergic axons
  • physiological role for NRP2 in bone homeostasis
  • SEMA3F and NRP2 are further regulators of human thymocyte migration in physiological and pathological conditions
  • NRP1 and NRP2 are transmembrane glycoproteins that are essential for Neural crest cells (NCCs) migration
  • NRP1, NRP2 play an essential role in coordinating NCC migration with fate specification
  • is a non-tyrosine kinase receptor frequently overexpressed in various malignancies
  • novel function of NRP2 as a regulator of endocytosis, which is enhanced in cancer cells and is often associated with increased metastatic potential and drug resistance
  • WDFY1 functioned downstream of NRP2 to promote endosome maturation, thereby influencing the endosomal trafficking of EGFR and the formation of autolysosomes responsible for the degradation of internalized cargo
  • regulation of WDFY1 transcription by NRP2 axis is a critical event in maintaining metastatic phenotype in cancer cells
  • 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
  • new role for NRP2 in the positioning of neurons during adult hippocampal neurogenesis, acting via the GSK3B signaling pathway
  • NRP1 and NRP2 are co-receptors for heparin-binding growth factors and class 3 semaphorins
    • CELLULAR PROCESS
    PHYSIOLOGICAL PROCESS nervous system
    PATHWAY
    metabolism
    signaling
    a component complexing with plexin (PLXNB1) to form semaphorin 3* receptors
    INTERACTION
    DNA
    RNA
    small molecule
    protein
  • receptors for the semaphorin family of axon guidance molecules, and is critical for development of the nervous system
  • interactions between NRP2 and secreted semaphorins function to coordinate repulsive axon guidance during neurodevelopment (Giger 1998)
  • transmembrane receptor for the lymphangiogenic vascular endothelial growth factor C (VEGFC), playing an important role in lymphatic vessel sprouting
  • interaction between NRP2 and FLT4 mediates proper lymphatic vessel sprouting in response to VEGFC
  • motoneuronal SEMA3C regulates the shared SEMA3 neuropilin receptors NRP1 and NRP2 levels in opposite ways at the growth cone surface
  • GATA2 and LMO2 cooperatively regulate VEGFA-induced angiogenesis and lymphangiogenesis via NRP2
  • controls endothelial cell migration and tumor angiogenesis by altering NRP2 expression
  • in thyroid cells PAX8 directly binds the Neuropilin-2 promoter leading to its transcriptional repression
  • SEMA3F provides neuronal guidance cues via its ability to bind neuropilin 2 (NRP2) and Plexin A family molecules
  • NRP2 inhibits WDFY1 transcription by preventing the nuclear localization of a transcription factor, BPTF
  • SEMA3G induces cell collapse in an NRP2/PLXND1-dependent manner
  • 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
  • NRCAM stabilizes binding between NRP2 and PLXNA3 necessary for SEMA3F-induced spine pruning
    • cell & other
    REGULATION
    ASSOCIATED DISORDERS
    corresponding disease(s)
    Other morbid association(s)
    TypeGene ModificationChromosome rearrangementProtein expressionProtein Function
    constitutional     --over  
    of tubular and interstitial NRP2 protein expression in patients with focal segmental glomerulosclerosis (FSGS)(Schramek 2009)
    constitutional   deletion    
    enhances detrusor contractility following bladder outlet obstruction
    tumoral     --over  
    in renal cell carcinoma
    Susceptibility to familial early-onset generalised osteoarthritis
    Variant & Polymorphism SNP increasing the risk of familial early-onset generalised osteoarthritis
    Candidate gene
    Marker
    Therapy target
    ANIMAL & CELL MODELS
  • severe impairement of developmental yolk sac and embryonic angiogenesis in double homozygotes Nrp1(-/-), Nrp2(-/-)
  • Nrp2 deletion in mice leads to increased bladder smooth muscle (BSM) contraction