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FLASH GENE
Symbol NRP2 contributors: mct - updated : 24-02-2017
HGNC name neuropilin 2
HGNC id 8005
Location 2q33.3      Physical location : 206.547.223 - 206.662.856
Synonym name
  • receptor for VEGF165 and semaphorins class3
  • vascular endothelial cell growth factor 165 receptor 2
  • Synonym symbol(s) VEGF165R2, NPP2, NP2, NPN2, PRO2714
    DNA
    TYPE functioning gene
    STRUCTURE 115.68 kb     20 Exon(s)
    10 Kb 5' upstream gene genomic sequence study
    text structure including exon 16b
    MAPPING cloned Y linked N status confirmed
    Map cen - D2S307 - NRP2 - D2S355 - qter
    Authors Rossignol (99)
    Physical map
    CYP20A1 2q33 cytochrome P450, family 20, subfamily A, polypeptide 1 ABI-2 2q33 abl-interactor 2 MRPL50P2 2q34 abl-interactor 2 RAPH1 2q33 Ras association (RalGDS/AF-6)and plekstrin homology 1 LOC344461 2q33.3 similar to ZNF207 protein CD28 2q33 CD28 antigen (Tp44) LOC344462 2q33.3 similar to Keratin, type I cytoskeletal 18 (Cytokeratin 18) (K18) (CK 18) CTLA4 2q33 cytotoxic T-lymphocyte-associated protein 4 ICOS 2q33 inducible T-cell co-stimulator ALS2CR19 2q33 amyotrophic lateral sclerosis 2 (juvenile) chromosome region, candidate 19 NRP2 2q34 neuropilin 2 LOC391473 2 similar to cyclophilin A FLJ20309 2q33.3 hypothetical protein FLJ20309 NDUFS1 2q33-q34 NADH dehydrogenase (ubiquinone) Fe-S protein 1, 75kDa (NADH-coenzyme Q reductase) EEF1B2 2q33 eukaryotic translation elongation factor 1 beta 2 GPR1 2q33.3 G protein-coupled receptor 1 KIAA1571 2q34 KIAA1571 protein LOC391474 2 hypothetical gene supported by AK123581 ADAM23 2q33 a disintegrin and metalloproteinase domain 23 LOC200726 2q34 hypothetical LOC200726 LOC391475 2 similar to Down syndrome critical region protein 3 (Down syndrome critical region protein A) LOC130752 KIAA0971 2p23.3-q34 Homo sapiens KIAA0971 protein (KIAA0971), mRNA. CPO 3q12 coproporphyrinogen oxidase (coproporphyria, harderoporphyria) KLF7 2q32 Kruppel-like factor 7 (ubiquitous) LOC389071 2 LOC389071 CREB1 2q32-q34 cAMP responsive element binding protein 1 LOC151194 2q34 similar to hepatocellular carcinoma-associated antigen HCA557b LOC391476 2 similar to PPP1R14B protein FLJ40432 2q34 hypothetical protein FLJ40432 FZD5 2q33-q34 frizzled homolog 5 (Drosophila) LOC389072 2 similar to RIKEN cDNA 9430067K14 gene; Ras GTPase-activating protein 1 (GTPase-activating protein) (GAP) (Ras p21 protein activator) (p120GAP) (RasGAP) LOC391477 2 similar to ribosomal protein L9; 60S ribosomal protein L9 LOC344471 2q34 similar to dJ999L4.1 (novel protein similar to ribosomal protein L12 (RPL12))
    RNA
    TRANSCRIPTS type messenger
    text likely other transcripts, divergence between a and b transcripts after amino acid 808
    identificationnb exonstypebpproduct
    ProteinkDaAAspecific expressionYearPubmed
    17 splicing 6671 104.8 931 - 2016 27026195
  • a 17 exons variant
  • containing exon 9b (shorter than 9a)
  • containing exon 15a (longer than 15b)
  • lacking exon 16
  • encoding for a 911 amino acids mature peptide (102.3 kDa)
  • also called NRP2a(22) or VEGF165R2
  • 16 splicing 6605 102.3 909 - 2016 27026195
  • also called NRP2a(0)
  • NRP2b and NRP2a differ only in their C-terminal regions
  • containing exons 9b & 15b (shorter than 9a & 15a respectively)
  • lacking exons 16 & 17
  • encoding for a 889 amino acids mature peptide (99.7 kDa)
  • 17 splicing 6656 104.3 926 - 2016 27026195
  • a 17 exons variant
  • containing exons 9b & 15b (shorter than 9a & 15a respectively)
  • lacking exon 16
  • encoding for a 906 amino acids mature peptide (101.8 kDa)
  • also called NRP2a(17)
  • 16 splicing 4148 101.4 901 - 2016 27026195
  • also called NRP2b(0)
  • NRP2b and NRP2a differ only in their C-terminal regions
  • containing exons 9b & 15b (shorter than 9a & 15a respectively)
  • lacking exons 17 & 18
  • encoding for a 881 amino acids mature peptide (98.9 kDa)
  • unlike NRP2a, NRP2b did not bind the PDZ domain scaffolding protein GAIP carboxyl terminus-interacting protein (GIPC1) and only weakly recruited phosphatase and tensin homolog (PTEN)
  • 16 splicing 4165 102 906 - 2016 27026195
  • a 16 exons variant
  • containing exon 9b (shorter than 9a)
  • containing exon 15a (longer than 15b)
  • lacking exons 17 & 18
  • encoding for a 886 amino acids mature peptide (99.5 kDa)
  • also called NRP2b(5)
  • 9 splicing 2601 62.4 555 - 2016 27026195
  • a 9 exons variant
  • containing exons 9a (longer than 9b)
  • lacking exons 10 to 18
  • encoding for a 535 amino acids mature peptide (59.9 kDa)
  • soluble isoform
  • also called s9NRP2b
  • EXPRESSION
    Type
       expressed in (based on citations)
    organ(s)
    SystemOrgan level 1Organ level 2Organ level 3Organ level 4LevelPubmedSpeciesStageRna symbol
    Cardiovascularheart    
     vessels    
    Lymphoid/Immunethymus     Homo sapiens
    Reproductivemale systemtestis    Homo sapiens
    Skin/Tegumentskin     Homo sapiens
    Urinarybladder     Homo sapiens
     kidneytubulecollecting duct   Homo sapiens
    tissue
    SystemTissueTissue level 1Tissue level 2LevelPubmedSpeciesStageRna symbol
    Muscularsmooth    Homo sapiens
    Muscularstriatumcardiac  
    cells
    SystemCellPubmedSpeciesStageRna symbol
    Cardiovascularendothelial cell
    cell lineage
    cell lines tumor cells
    fluid/secretion
    at STAGE
    physiological period fetal, pregnancy
    Text in the developing nervous system,placenta
    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
  • 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