Affinage

NRP2

Neuropilin-2 · UniProt O60462

Length
931 aa
Mass
104.8 kDa
Annotated
2026-04-29
67 papers in source corpus 26 papers cited in narrative 29 extracted findings

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

NRP2 is a transmembrane co-receptor that integrates semaphorin and VEGF family signals to regulate neural circuit formation, vascular development and integrity, immune cell function, and bone homeostasis. It forms signaling complexes with plexins (PlexinA1, PlexinD1) and VEGF receptors, transducing class 3 semaphorin signals (SEMA3F, SEMA3C, SEMA3G) to control axon guidance, sympathetic gangliogenesis, and dendrite morphogenesis, while activating downstream cascades including LATS1/YAP, FAK, SSH1/cofilin, and MAPK pathways in vascular and cancer contexts (PMID:22790009, PMID:28731029, PMID:36720439, PMID:32983407, PMID:40402249, PMID:19). In endothelial cells, NRP2 maintains adherens junction stability through VE-cadherin/p120 catenin interactions, promotes integrin α5 recycling, and its transcription is regulated by GATA2, FOXA1, and SMAD2 (PMID:32528960, PMID:35028975, PMID:39435415, PMID:36306654). NRP2 also functions as a host entry receptor for Lujo virus and cytomegalovirus pentamer complex, serves as an anti-inflammatory receptor on macrophages engaged by the HARS splice variant HARSWHEP, and acts as a co-inhibitory checkpoint receptor on CD4+ T effector cells (PMID:29120745, PMID:41805587, PMID:40073151). In macrophages, NRP2 transferred via migrasomes binds PROX1 to drive CD5L expression and efferocytosis, and alveolar macrophage-derived NRP2 enhances neutrophil bactericidal activity (PMID:41361466, PMID:35435271).

Mechanistic history

Synthesis pass · year-by-year structured walk · 17 steps
  1. 2012 High

    Establishing NRP2 as a semaphorin co-receptor in neural development: NRP2 was shown to transduce SEMA3F signals to guide sympathetic neural crest cell migration and gangliogenesis, with genetic epistasis revealing cooperation between NRP1 and NRP2.

    Evidence Compound NRP1/NRP2/SEMA3A/SEMA3F knockout mice with phenotypic analysis of sympathetic nervous system organization

    PMID:22790009

    Open questions at the time
    • Downstream intracellular signaling pathway in sympathetic neurons not defined
    • Relative contributions of individual plexin co-receptors not resolved
  2. 2012 Low

    Identifying NRP2 as a target of miRNA regulation with downstream MEK-ERK pathway engagement: miR-15b was shown to directly target the NRP2 3′UTR, and NRP2 loss deactivated MEK-ERK signaling in glioma cells.

    Evidence Luciferase reporter assay confirming miR-15b binding to NRP2 3′UTR, Western blot for MEK-ERK pathway components

    PMID:23142217

    Open questions at the time
    • Indirect evidence for MEK-ERK link — no direct NRP2-MEK interaction shown
    • Single lab, not independently validated
  3. 2013 Medium

    Extending NRP2 function beyond neural tissue to bone homeostasis: NRP2 knockout mice displayed trabecular bone loss with altered osteoclast/osteoblast numbers, establishing a non-neuronal developmental role.

    Evidence Nrp2 knockout mice with histomorphometry and immunohistochemistry of bone

    PMID:23598046

    Open questions at the time
    • Semaphorin ligand specificity in bone remodeling not defined
    • Cell-autonomous vs. paracrine roles of NRP2 in osteoblasts versus osteoclasts unresolved
  4. 2016 Medium

    Revealing a non-canonical transcriptional regulatory function: NRP2 was found to prevent nuclear entry of the transcription factor FAC1, thereby suppressing WDFY1 transcription and maintaining endocytic activity in cancer cells — a function independent of its classical co-receptor role.

    Evidence NRP2 knockdown/overexpression with subcellular fractionation and reporter assays for WDFY1 promoter

    PMID:27026195

    Open questions at the time
    • Mechanism by which NRP2 sequesters FAC1 from the nucleus is unclear
    • Generalizability beyond metastatic cancer cells not tested
  5. 2017 High

    Demonstrating NRP2 as a cell-type-specific determinant of neural circuit formation and social behavior: mitral cell-specific NRP2 knockout abolished the olfactory bulb-to-amygdala circuit and eliminated odor-induced social attraction, directly linking NRP2/SEMA3F to behavioral output.

    Evidence Mitral cell-specific Nrp2 conditional knockout mice with circuit tracing, in utero electroporation rescue, and behavioral assays

    PMID:28731029

    Open questions at the time
    • Downstream signaling in mitral cells not dissected
    • Whether NRP2 acts through PlexinA1 or other plexins in this circuit is unknown
  6. 2017 High

    Identifying NRP2 as a viral entry receptor: a genome-wide haploid screen revealed that the Lujo virus glycoprotein binds the NRP2 N-terminal domain, and NRP2 knockout cells were resistant to infection — establishing a pathogen co-option of a developmental receptor.

    Evidence Haploid genetic screen, NRP2 knockout and overexpression infection assays, direct glycoprotein-NRP2 binding

    PMID:29120745

    Open questions at the time
    • Post-binding entry mechanism (endocytic route, pH dependence) not fully defined
    • Whether NRP2 splice variants differ in receptor function for LUJV not tested
  7. 2020 Medium

    Defining NRP2's role in endothelial integrin trafficking and adhesion: NRP2 was shown to promote ITGA5 recycling and Rac-1-dependent adhesion/migration on fibronectin, independent of VEGF stimulation, distinguishing a VEGF-independent endothelial function.

    Evidence NRP2 siRNA knockdown with integrin recycling assays, Rac-1 activity measurements, adhesion/migration assays in endothelial cells

    PMID:32528960

    Open questions at the time
    • Direct physical interaction between NRP2 and ITGA5 not demonstrated
    • Whether this mechanism operates in vivo during angiogenesis is untested
  8. 2020 Medium

    Uncovering the SSH1/cofilin/actin axis as a VEGF-independent NRP2 signaling pathway: NRP2 activated the cofilin phosphatase SSH1, driving F-actin polymerization and endothelial migration in pancreatic neuroendocrine tumor angiogenesis.

    Evidence NRP2 knockdown/overexpression with SSH1 epistasis, mutant constructs, tube formation assays, in vivo antibody blockade

    PMID:32983407

    Open questions at the time
    • How NRP2 activates SSH1 at the molecular level is unknown
    • Whether SSH1/cofilin pathway engagement requires a plexin co-receptor not addressed
  9. 2021 Medium

    Establishing SMAD2 as a direct transcriptional activator of NRP2: TGFβ-activated SMAD2 bound the NRP2 promoter and upregulated expression in endometrial stromal cells, linking NRP2 to EMT and invasion programs.

    Evidence ChIP and luciferase reporter assays confirming SMAD2 binding; NRP2 siRNA with TGFβ rescue

    PMID:36306654

    Open questions at the time
    • SMAD2 binding site in NRP2 promoter not precisely mapped
    • Whether SMAD3 or SMAD4 co-participate not tested
  10. 2022 Medium

    Defining transcriptional regulation of NRP2 by GATA2 and FOXA1, and linking NRP2 to atherosclerosis: GATA2 directly activates NRP2 transcription (binding −1100 to +100 bp), while FOXA1 suppresses it; NRP2 upregulates PARP1 to promote endothelial apoptosis under disturbed flow, and knockdown in Apoe−/− mice attenuates plaque development.

    Evidence ChIP assays, promoter reporter assays, NRP2 knockdown in HUVECs and Apoe−/− mice, PARP1 expression analysis

    PMID:35028975 PMID:36764279 PMID:39435415

    Open questions at the time
    • How NRP2 mechanistically upregulates PARP1 protein is unclear
    • Relative importance of GATA2 versus FOXA1 in different vascular beds not established
  11. 2022 Medium

    Demonstrating NRP2 activation of FAK in glioblastoma: NRP2 directly bound and activated FAK; knockdown abolished FAK phosphorylation and tumor cell invasion, while FAK agonist rescued NRP2 loss in vivo.

    Evidence Co-binding assays, FAK phosphorylation Western blot, NRP2 knockdown with FAK agonist rescue in vivo tumor model

    PMID:41861662

    Open questions at the time
    • Whether FAK activation requires plexin co-receptors or ligand stimulation is not resolved
    • Structural basis of NRP2-FAK interaction unknown
  12. 2022 Medium

    Revealing a paracrine immune function: alveolar macrophage-derived NRP2 bound neutrophils and enhanced their phagocytic and bactericidal capacity via TLR4/TNF-α upregulation; conditional NRP2 deletion in macrophages impaired bacterial clearance in pneumonia.

    Evidence Conditional NRP2 KO in alveolar macrophages, NRP2-neutrophil binding assays, E. coli pneumonia model

    PMID:35435271

    Open questions at the time
    • Form of NRP2 released by macrophages (shed ectodomain vs. exosomal) not defined
    • Receptor on neutrophils that binds NRP2 not identified
  13. 2023 Medium

    Mapping NRP2/PlexinA1 to the Hippo pathway: SEMA3G signaling through NRP2/PlexinA1 inhibited LATS1 kinase and activated YAP to drive vascular smooth muscle cell proliferation, providing a defined intracellular cascade downstream of the receptor complex.

    Evidence SEMA3G treatment of human aortic SMCs, NRP2/PlexinA1 inhibition, Western blot for LATS1/YAP, diabetic mouse model

    PMID:36720439

    Open questions at the time
    • Mechanism by which NRP2/PlexinA1 inhibits LATS1 not defined
    • Whether this pathway operates in endothelial cells or only SMCs is unclear
  14. 2025 High

    Identifying HARSWHEP as a selective NRP2 ligand with anti-inflammatory function: the histidyl-tRNA synthetase splice variant bound NRP2 via a helix-turn-helix motif, suppressing proinflammatory receptor expression in macrophages, validated structurally and in disease models.

    Evidence Structural analysis, binding specificity assays, primary human macrophage assays, in vivo interstitial lung disease models, clinical trial in sarcoidosis

    PMID:40073151

    Open questions at the time
    • Downstream signaling cascade triggered by HARSWHEP-NRP2 engagement in macrophages not mapped
    • Whether HARSWHEP competes with semaphorins for NRP2 binding not determined
  15. 2025 Medium

    Extending the viral receptor function to cytomegalovirus: NRP2 served as an endocytic receptor for GPCMV pentamer complex; double knockout of NRP2 and PDGFRA abolished infection, with NRP2 re-expression rescuing entry.

    Evidence Co-immunoprecipitation of NRP2 with pentamer complex, CRISPR KO of NRP2/PDGFRA, ectopic expression rescue, infection assays

    PMID:41805587

    Open questions at the time
    • Whether human CMV uses NRP2 similarly not directly tested
    • Endocytic route following NRP2-mediated entry not characterized
  16. 2025 Medium

    Demonstrating NRP2 in migrasome-mediated intercellular communication: NRP2 transferred via migrasomes from hypoxic CRC cells to macrophages bound PROX1 and drove CD5L expression/efferocytosis, linking NRP2 to tumor immune evasion.

    Evidence Co-immunoprecipitation of NRP2-PROX1, migrasome characterization, scRNA-seq, in vivo liver metastasis model

    PMID:41361466

    Open questions at the time
    • NRP2-PROX1 interaction not validated by reciprocal IP or structural methods
    • Whether NRP2 is functional as a receptor versus a cargo inside migrasomes is unclear
  17. 2025 Medium

    Structural validation of the NRP2/PlexinA1 signaling complex: a bispecific antibody that dimerizes PlexinA1 and NRP2 mimicked SEMA3F tumor-suppressive signaling (inhibiting phospho-AKT and proliferation), confirming that enforced NRP2/PlexinA1 proximity is sufficient for signal transduction.

    Evidence Bispecific antibody engineering, structural studies of binding epitopes, phospho-AKT and proliferation assays

    PMID:41391772

    Open questions at the time
    • Whether endogenous SEMA3F engagement produces identical downstream signaling profiles not compared side by side
    • In vivo tumor suppressive efficacy of the bispecific antibody not yet reported

Open questions

Synthesis pass · forward-looking unresolved questions
  • Key unresolved questions include: the structural basis of NRP2 intracellular signaling (given its short cytoplasmic tail), identification of direct cytoplasmic effectors, how NRP2 differentially engages plexin versus VEGFR co-receptors in distinct cell types, and the physiological relevance of NRP2 as a co-inhibitory T cell checkpoint.
  • No structural model of full-length NRP2 in complex with any plexin
  • Cytoplasmic domain interactome not systematically characterized
  • T cell checkpoint function reported only in preprint

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0060089 molecular transducer activity 5 GO:0098772 molecular function regulator activity 5 GO:0001618 virus receptor activity 2
Localization
GO:0005886 plasma membrane 4 GO:0005576 extracellular region 2
Pathway
R-HSA-162582 Signal Transduction 5 R-HSA-1266738 Developmental Biology 4 R-HSA-1643685 Disease 3 R-HSA-168256 Immune System 2
Partners
FAKHARSPLXNA1PLXND1SEMA3CSEMA3FSEMA3GSSH1
Complex memberships
NRP2/PlexinA1 semaphorin receptor complexNRP2/PlexinD1 semaphorin receptor complexNRP2/VEGFR2 VEGF receptor complex

Evidence

Reading pass · 29 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2017 NRP2 serves as a host cell entry receptor for Lujo virus (LUJV); the LUJV glycoprotein binds the N-terminal domain of NRP2, and overexpression of NRP2 or its N-terminal domain enhances VSV-LUJV infection while cells lacking NRP2 are deficient in wild-type LUJV infection. Genome-wide haploid genetic screen, overexpression/knockout cell assays, direct binding assay Cell host & microbe High 29120745
2012 NRP2 (along with NRP1) acts as a receptor for class 3 semaphorins (SEMA3A, SEMA3F) to guide sympathetic neural crest cells; NRP2/SEMA3F signaling controls gangliogenesis and prevents ectopic neurite extension along the embryonic aorta, while NRP1 and NRP2 cooperate for sympathetic nervous system organization as shown by compound mutant analysis. Genetic epistasis using knockout mice (NRP1 KO, NRP2 KO, SEMA3A KO, SEMA3F KO, compound mutants), lineage-specific conditional knockout, phenotypic analysis Developmental biology High 22790009
2017 Nrp2 expressed on mitral cells (second-order olfactory neurons) is required and sufficient for circuit formation from the posteroventral main olfactory bulb to the anterior medial amygdala; Semaphorin 3F (a repulsive Nrp2 ligand) regulates both migration of Nrp2+ mitral cells and their axonal projection; MC-specific Nrp2 knockout impairs this circuit and eliminates odour-induced attractive social responses. MC-specific Nrp2 knockout mice, in utero electroporation, behavioral assays, anatomical circuit tracing Nature communications High 28731029
2016 NRP2 inhibits WDFY1 transcription by preventing nuclear localization of the transcription factor FAC1 (Fetal ALZ50-reactive clone 1), thereby maintaining endocytic activity in metastatic cancer cells; this represents a non-co-receptor transcriptional regulatory function of NRP2. NRP2 knockdown/overexpression, subcellular fractionation, reporter assays, FAC1 nuclear localization imaging Scientific reports Medium 27026195
2013 Nrp2 deficiency in mice leads to trabecular bone loss accompanied by increased osteoclast numbers and decreased osteoblast counts, establishing a role for NRP2 in bone homeostasis; Nrp2 is expressed in both osteoblasts and osteoclasts and its coreceptors (Plexin A family, Plexin D1) and class 3 semaphorin ligands are expressed during osteogenic differentiation. Nrp2 knockout mice, histomorphometry, immunohistochemistry, in vitro osteoblast/osteoclast differentiation assays Bone Medium 23598046
2020 NRP2 promotes endothelial cell adhesion and migration over fibronectin matrices via Rac-1, independent of β3 integrin or VEGF stimulation; NRP2 depletion upregulates α5 integrin (ITGA5) expression and disrupts its cellular organization, and NRP2 promotes ITGA5 recycling in endothelial cells. NRP2 siRNA knockdown, adhesion/migration assays, integrin recycling assays, Rac-1 activity assays, Western blot Frontiers in cell and developmental biology Medium 32528960
2020 NRP2 promotes PNET (pancreatic neuroendocrine tumor) angiogenesis via a VEGF/VEGFR2-independent pathway by activating the SSH1/cofilin/actin axis: NRP2 activates cofilin phosphatase slingshot-1 (SSH1), which dephosphorylates cofilin and induces F-actin polymerization to drive HUVEC migration; silencing SSH1 abrogates NRP2-activated migration. NRP2 knockdown/overexpression, mutant plasmid constructs, Western blot, immunofluorescence, wound-healing/tube formation assays, in vivo mouse model with NRP2 antibody blockade Cell & bioscience Medium 32983407
2022 NRP2 upregulates PARP1 protein expression under low shear stress (LSS) to promote endothelial cell apoptosis and atherosclerosis; the upstream transcription factor GATA2 regulates NRP2 expression in this context; NRP2 knockdown in Apoe−/− mice mitigates atherosclerosis development. NRP2 knockdown/overexpression in HUVECs, GATA2 transcription factor analysis, Western blot for PARP1 and apoptosis markers, in vivo Apoe−/− mouse model FASEB journal Medium 35028975
2023 GATA2 regulates NRP2 transcription by binding to the −1100 to +100 bp region of the NRP2 promoter; NRP2 forms a complex with VEGF-C under disturbed flow; quercetin inhibits NRP2-VEGFC complex formation to reduce endothelial inflammation. GATA2 promoter binding assay, NRP2-VEGFC co-immunoprecipitation, NRP2 knockdown in HUVECs and Apoe−/− mice International immunopharmacology Medium 36764279
2021 CAF-derived NRP2 promotes chemoresistance in gastric cancer through VEGF/NRP2 signaling that drives SDF-1 secretion and activates the Hippo pathway (YAP/TAZ) in cancer cells; NRP2 knockdown in CAFs reduces SDF-1 secretion and sensitizes cancer cells to 5-FU via DNA damage. NRP2 knockdown in primary CAFs, 3D co-culture, RNA-sequencing, cell viability/apoptosis assays, YAP/TAZ pathway analysis Gastric cancer Medium 34826008
2022 MUC16 regulates NRP2 expression via the JAK2/STAT1 signaling axis in pancreatic ductal adenocarcinoma; NRP2 knockdown in MUC16-overexpressing cells decreases cell adhesion and migration, placing NRP2 downstream of JAK2/STAT1 in MUC16-driven metastasis. RNA-sequencing, NRP2 knockdown, JAK2/STAT1 pathway inhibition, cell adhesion/migration assays, in vivo mouse model Molecular cancer research Medium 35533267
2020 NRP2 expression in bladder cancer correlates with GLI2 transcript levels; TGFβ1 regulates NRP2 and GLI2 expression and NRP2 binds TGFβ1, associates with TGFβ receptors, and enhances TGFβ1 signaling to promote EMT; NRP2 knockout/knockdown identifies SPP1/osteopontin as a downstream target positively regulated by NRP2. NRP2 KO and KD models, PCR profiling array (84 EMT genes), TGFβ1 treatment, TCGA correlation analysis, NRP2-TGFβ1 binding reported Frontiers in oncology Medium 32038994
2025 HARSWHEP (a splice variant of histidyl-tRNA synthetase) binds specifically and selectively to NRP2 via a helix-turn-helix motif; this interaction inhibits expression of proinflammatory receptors and cytokines and downregulates inflammatory pathways in primary human macrophages; structural analysis confirmed the binding motif. Structural analysis, binding specificity assays, primary human macrophage functional assays, in vivo animal models of ILD, clinical trial (sarcoidosis) Science translational medicine High 40073151
2023 Sema3G activates YAP and promotes VSMC (vascular smooth muscle cell) proliferation and migration via Nrp2/PlexinA1 signaling; Sema3G inhibits LATS1 kinase and thereby activates YAP downstream of Nrp2/PlexinA1; pharmacological inhibition of Nrp2/PlexinA1 or YAP (verteporfin) mitigates these effects. Sema3G treatment of HASMCs, NRP2/PlexinA1 inhibition, Western blot for LATS1/YAP, cell proliferation/migration assays, diabetic mouse model Cellular signalling Medium 36720439
2025 CAF-derived SEMA3C binds to the NRP2 receptor on liver metastasis-initiating cells and activates the MAPK pathway to promote colorectal cancer liver metastasis; confirmed by in vivo and in vitro experiments. Ligand-receptor interaction (SEMA3C-NRP2), in vivo metastasis models, MAPK pathway activation assays, spatial transcriptomics/time-resolved analysis Proceedings of the National Academy of Sciences of the United States of America Medium 40402249
2022 Alveolar macrophage-derived NRP2 binds to CD11b+ Ly6Glo/+ neutrophils and enhances their phagocytosis and bacterial killing capacity, partially through increased TLR4 and TNF-α expression; conditional deletion of NRP2 in alveolar macrophages results in persistent bacteria and decreased survival in E. coli pneumonia. Conditional NRP2 KO in alveolar macrophages, in vitro NRP2-neutrophil binding assays, phagocytosis/killing assays, in vivo E. coli pneumonia model Journal of leukocyte biology Medium 35435271
2022 FOXA1 binds the NRP2 promoter to suppress NRP2 transcription in vascular endothelial cells; LPS-induced FOXA1 elevation reduces NRP2 expression, thereby promoting endothelial cell injury; NRP2 knockdown offsets the protective effect of FOXA1 knockdown. ChIP assay, dual-luciferase reporter assay, siRNA knockdown, LPS-stimulated HUVECs, cell viability/apoptosis assays Cytotechnology Medium 39435415
2021 TGFβ signaling activates SMAD2 which transcriptionally upregulates NRP2 expression in ectopic endometrial stromal cells; NRP2 depletion restrains ectopic ESC migration, invasion, and EMT; TGFβ treatment rescues NRP2 silencing-induced suppression. ChIP assay, luciferase reporter assay, SMAD2 activation, NRP2 siRNA knockdown, Transwell invasion/migration assays Reproductive biology Medium 36306654
2022 VEGF-A basolateral stimulation of endothelial cells induces a redistribution of NRP2 (and VEGFR2) toward the basolateral membrane domain; under unstimulated conditions NRP2 is evenly distributed across apical and basolateral membrane compartments. Immunocytochemistry, confocal imaging, fluorescence intensity quantification at apical vs. basolateral membranes of polarized HUVECs on Transwell inserts The journal of histochemistry and cytochemistry Medium 35876388
2022 NRP2 activates the focal adhesion kinase (FAK) signaling pathway through direct binding, promoting GBM cell proliferation, migration, and invasion; NRP2 knockdown inhibits FAK phosphorylation; activated FAK reverses NRP2 KD phenotype in vivo. NRP2 knockdown, FAK phosphorylation Western blot, co-binding assays, in vitro invasion/proliferation assays, in vivo tumor model with FAK agonist rescue Translational oncology Medium 41861662
2025 NRP2 functions as a co-inhibitory receptor on CD4+ T effector cells; NRP2 knockout results in hyperactive CD4+ T cell responses; NRP2 is co-expressed with PD-1, CTLA4, TIGIT, LAG3, and TIM3 on late effector/exhausted T cells; the co-inhibitory function is specific to T effectors and not T regulatory cells. Humanized SCID mice, NRP2 global and CD4+ T cell-specific KO, delayed-type hypersensitivity and cardiac transplant models, in vitro Treg suppression assays bioRxivpreprint Medium
2025 NRP2 stabilizes adherens junctions in endothelial cells by promoting the interaction between VE-cadherin and p120 catenin, maintaining surface availability of VE-cadherin; endothelial-specific Nrp2 knockout mice display hyperpermeable retinal vasculature and enhanced pro-inflammatory cytokine/adhesion molecule expression and increased aortic plaque development. Endothelial-specific Nrp2 conditional KO mouse, immortalized EC culture, VE-cadherin/p120 catenin interaction assays, retinal vascular permeability assay, inflammation marker analysis bioRxivpreprint Medium
2025 NRP2 is an endocytic pathway receptor for guinea pig cytomegalovirus (GPCMV) pentamer complex (PC); NRP2 interacts with PC in immunoprecipitation assays; double knockout of PDGFRA and NRP2 completely blocks GPCMV infection; ectopic expression of guinea pig NRP2 restores infection in knockout cells. Immunoprecipitation, CRISPR knockout of NRP2 and PDGFRA, ectopic receptor expression rescue, infection assays The Journal of general virology Medium 41805587
2025 SEMA3C inhibits cortical neuron dendrite outgrowth via NRP2 (and PLXND1) receptors; genetic reduction of astrocyte SEMA3C in Rett syndrome model mice enhances dendritic arborization and normalizes synaptic activity via the SEMA3C-NRP2-PLXND1 signaling pathway. Astrocyte-neuron co-culture, NRP2/PLXND1 receptor blocking, in vivo conditional Sema3C reduction in RTT mice, dendritic morphology analysis, electrophysiology bioRxivpreprint Medium
2025 A bispecific antibody dimerizing PLXNA1 and NRP2 mimics SEMA3F signaling and activates NRP2-mediated tumor-suppressive activity (inhibiting phospho-AKT, oncogene expression, and cell proliferation); structural studies show the bsAb binds PLXNA1/NRP2 at sites distinct from the SEMA3F-binding site but allows proper spacing for receptor complex formation. Bispecific antibody development, receptor dimerization assays, phospho-AKT assays, cell proliferation assays, structural studies The Journal of biological chemistry Medium 41391772
2022 CPSF4 binds to the promoters of NRP2 and VEGF and activates their transcription; CPSF4/VEGF/NRP2 signaling promotes tumor-initiating phenotype through TAZ induction; selective inhibition of NRP2 suppresses CPSF4-mediated effects. Chromatin immunoprecipitation (ChIP), NRP2 promoter reporter assays, NRP2 knockdown/inhibition, TAZ pathway analysis, in vitro and in vivo tumor models Medical oncology Low 36567417
2025 NRP2 (enriched in migrasomes from hypoxic colorectal cancer cells) is transferred to macrophages where it binds PROX1 to drive CD5L expression and upregulate efferocytosis receptors; NRP2 knockdown in CRC cells abrogates migrasome-induced CD5L+ macrophage polarization. NRP2 knockdown, co-immunoprecipitation (NRP2-PROX1 binding), migrasome characterization, scRNA-seq, in vivo liver metastasis model Journal of translational medicine Medium 41361466
2012 miR-15b attenuates NRP-2 protein expression by binding to the NRP-2 3'UTR (confirmed by luciferase assay), and this miR-15b/NRP-2 axis deactivates the MEK-ERK pathway in glioma cells to reduce invasion and tube formation. Luciferase activity assay, in vitro invasion assay, tube formation assay, Western blot/pathway analysis Cancer letters Low 23142217
2025 In vitro binding assays show NRP2 (but not NRP1) binds both SARS-CoV-2 spike fragments S1 and S1', while NRP1 exclusively binds S1; SARS-CoV-2 RNA was detected in NRP2-positive, ACE2/TMPRSS2-negative cell clusters (alveolar macrophages, mast cells) in vivo, supporting a role for NRP2 in systemic viral dissemination. In vitro immunofluorescence binding assay, immunohistochemistry, CODEX spatial multiplex immunofluorescence, scRNA-seq re-analysis Journal of virology Low 41159753

Source papers

Stage 0 corpus · 67 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2012 MiR-15b and miR-152 reduce glioma cell invasion and angiogenesis via NRP-2 and MMP-3. Cancer letters 136 23142217
2006 Arabidopsis NRP1 and NRP2 encode histone chaperones and are required for maintaining postembryonic root growth. The Plant cell 110 17122067
2017 NRP2 and CD63 Are Host Factors for Lujo Virus Cell Entry. Cell host & microbe 107 29120745
2012 NRP1 and NRP2 cooperate to regulate gangliogenesis, axon guidance and target innervation in the sympathetic nervous system. Developmental biology 66 22790009
2018 NRP-2 in tumor lymphangiogenesis and lymphatic metastasis. Cancer letters 63 29339213
2023 Sonodynamic Therapy of NRP2 Monoclonal Antibody-Guided MOFs@COF Targeted Disruption of Mitochondrial and Endoplasmic Reticulum Homeostasis to Induce Autophagy-Dependent Ferroptosis. Advanced science (Weinheim, Baden-Wurttemberg, Germany) 52 37661565
2016 MicroRNA-331-3p Suppresses Cervical Cancer Cell Proliferation and E6/E7 Expression by Targeting NRP2. International journal of molecular sciences 48 27548144
2016 Pathway-related molecules of VEGFC/D-VEGFR3/NRP2 axis in tumor lymphangiogenesis and lymphatic metastasis. Clinica chimica acta; international journal of clinical chemistry 46 27527412
2013 Nrp2 deficiency leads to trabecular bone loss and is accompanied by enhanced osteoclast and reduced osteoblast numbers. Bone 42 23598046
2020 NRP2 as an Emerging Angiogenic Player; Promoting Endothelial Cell Adhesion and Migration by Regulating Recycling of α5 Integrin. Frontiers in cell and developmental biology 41 32528960
2021 CAF promotes chemoresistance through NRP2 in gastric cancer. Gastric cancer : official journal of the International Gastric Cancer Association and the Japanese Gastric Cancer Association 40 34826008
2007 Association of the neuropilin-2 (NRP2) gene polymorphisms with autism in Chinese Han population. American journal of medical genetics. Part B, Neuropsychiatric genetics : the official publication of the International Society of Psychiatric Genetics 40 17427189
2021 FOXM1 accelerates wound healing in diabetic foot ulcer by inducing M2 macrophage polarization through a mechanism involving SEMA3C/NRP2/Hedgehog signaling. Diabetes research and clinical practice 37 34742786
2017 Nrp2 is sufficient to instruct circuit formation of mitral-cells to mediate odour-induced attractive social responses. Nature communications 36 28731029
2007 Myeloid leukemias express a broad spectrum of VEGF receptors including neuropilin-1 (NRP-1) and NRP-2. Leukemia & lymphoma 29 17917967
2022 MUC16 Promotes Liver Metastasis of Pancreatic Ductal Adenocarcinoma by Upregulating NRP2-Associated Cell Adhesion. Molecular cancer research : MCR 26 35533267
2020 miR-331-3p Suppresses Cell Proliferation in TNBC Cells by Downregulating NRP2. Technology in cancer research & treatment 26 32174262
2022 The dual role of boron in vitro neurotoxication of glioblastoma cells via SEMA3F/NRP2 and ferroptosis signaling pathways. Environmental toxicology 25 36136913
2020 Linking NRP2 With EMT and Chemoradioresistance in Bladder Cancer. Frontiers in oncology 25 32038994
2018 ARFHPV E7 oncogene, lncRNA HOTAIR, miR-331-3p and its target, NRP2, form a negative feedback loop to regulate the apoptosis in the tumorigenesis in HPV positive cervical cancer. Journal of cellular biochemistry 25 29130509
2022 NRP2 promotes atherosclerosis by upregulating PARP1 expression and enhancing low shear stress-induced endothelial cell apoptosis. FASEB journal : official publication of the Federation of American Societies for Experimental Biology 24 35028975
2019 miR-331-3p suppresses cell invasion and migration in colorectal carcinoma by directly targeting NRP2. Oncology letters 22 31807170
2016 NRP2 transcriptionally regulates its downstream effector WDFY1. Scientific reports 22 27026195
2021 Stress response proteins NRP1 and NRP2 are pro-survival factors that inhibit cell death during ER stress. Plant physiology 21 34618053
2022 Circ_CHFR Promotes Platelet-Derived Growth Factor-BB-Induced Proliferation, Invasion, and Migration in Vascular Smooth Muscle Cells via the miR-149-5p/NRP2 Axis. Journal of cardiovascular pharmacology 20 33990513
2020 The histone methylation readers MRG1/MRG2 and the histone chaperones NRP1/NRP2 associate in fine-tuning Arabidopsis flowering time. The Plant journal : for cell and molecular biology 19 32324922
2018 Low Expression of miR-466f-3p Sustains Epithelial to Mesenchymal Transition in Sonic Hedgehog Medulloblastoma Stem Cells Through Vegfa-Nrp2 Signaling Pathway. Frontiers in pharmacology 18 30483126
2006 Hormonal regulation and differential expression of neuropilin (NRP)-1 and NRP-2 genes in bovine granulosa cells. Reproduction (Cambridge, England) 18 16514198
2019 Expression of NRP-1 and NRP-2 in Endometrial Cancer. Current pharmaceutical biotechnology 17 30806307
2022 LRP11-AS1 promotes the proliferation and migration of triple negative breast cancer cells via the miR-149-3p/NRP2 axis. Cancer cell international 16 35279146
2021 Circ-LDLRAD3 Enhances Cell Growth, Migration, and Invasion and Inhibits Apoptosis by Regulating MiR-224-5p/NRP2 Axis in Gastric Cancer. Digestive diseases and sciences 15 33389349
2020 Vascular NRP2 triggers PNET angiogenesis by activating the SSH1-cofilin axis. Cell & bioscience 13 32983407
2020 MiR-146a Regulates Migration and Invasion by Targeting NRP2 in Circulating-Tumor Cell Mimicking Suspension Cells. Genes 12 33396906
2023 Uterine inflammatory myofibroblastic tumor harboring novel NUDCD3-ROS1 and NRP2-ALK fusions: clinicopathologic features of 4 cases and literature review. Virchows Archiv : an international journal of pathology 11 36624188
2023 Quercetin protects endothelial function from inflammation induced by localized disturbed flow by inhibiting NRP2 -VEGFC complex. International immunopharmacology 11 36764279
2024 miR-200-mediated inactivation of cancer-associated fibroblasts via targeting of NRP2-VEGFR signaling attenuates lung cancer invasion and metastasis. Molecular therapy. Nucleic acids 10 38766528
2023 Sema3G activates YAP and promotes VSMCs proliferation and migration via Nrp2/PlexinA1. Cellular signalling 9 36720439
2022 Exosomal miR-328 originated from pulmonary adenocarcinoma cells enhances osteoclastogenesis via downregulating Nrp-2 expression. Cell death discovery 9 36192384
2025 Cancer-associated fibroblast-derived SEMA3C facilitates colorectal cancer liver metastasis via NRP2-mediated MAPK activation. Proceedings of the National Academy of Sciences of the United States of America 8 40402249
2022 A Novel circUBR4/miR-491-5p/NRP2 ceRNA Network Regulates Oxidized Low-density Lipoprotein-induced Proliferation and Migration in Vascular Smooth Muscle Cells. Journal of cardiovascular pharmacology 7 34935701
2022 Alveolar macrophage-derived NRP2 curtails lung injury while boosting host defense in bacterial pneumonia. Journal of leukocyte biology 7 35435271
2022 The activation of TGF-β signaling promotes cell migration and invasion of ectopic endometrium by targeting NRP2. Reproductive biology 6 36306654
2023 Tumor Necrosis Factor and Interleukin-1β Upregulate NRP2 Expression and Promote SARS-CoV-2 Proliferation. Viruses 5 37515185
2022 Ruscogenin Attenuates Lipopolysaccharide-Induced Septic Vascular Endothelial Dysfunction by Modulating the miR-146a-5p/NRP2/SSH1 Axis. Drug design, development and therapy 5 35440867
2022 CPSF4 promotes tumor-initiating phenotype by enhancing VEGF/NRP2/TAZ signaling in lung cancer. Medical oncology (Northwood, London, England) 5 36567417
2021 NRP2, a potential biomarker for oral squamous cell carcinoma. American journal of translational research 5 34540006
2015 Preparation, Purification, and Identification of a Monoclonal Antibody Against NRP2 b1b2 Domain. Monoclonal antibodies in immunodiagnosis and immunotherapy 5 26492624
2025 A human histidyl-tRNA synthetase splice variant therapeutic targets NRP2 to resolve lung inflammation and fibrosis. Science translational medicine 3 40073151
2024 MiR-331-3p facilitates osteoporosis and may promote osteoporotic fractures by modulating NRP2 expression. Journal of orthopaedic surgery and research 3 39154011
2024 FOXA1 exacerbates LPS-induced vascular endothelial cell injury in sepsis by suppressing the transcription of NRP2. Cytotechnology 3 39435415
2023 Association of plasma NRP2 and VEGF-C levels with prostate cancer disease severity. The Prostate 3 37942701
2022 Single dose S-ketamine rescues transcriptional dysregulation of Mtor and Nrp2 in the prefrontal cortex of FSL rats 1 hour but not 14 days post dosing. European neuropsychopharmacology : the journal of the European College of Neuropsychopharmacology 3 36375239
2020 Segregation Analysis of Rare NRP1 and NRP2 Variants in Families with Lymphedema. Genes 3 33212964
2025 MBsNRP2-based ultrasound molecular imaging for early diagnosis of castration-resistant prostate cancer. BMC cancer 2 40275166
2022 Quantitative Assessment of the Apical and Basolateral Membrane Expression of VEGFR2 and NRP2 in VEGF-A-stimulated Cultured Human Umbilical Vein Endothelial Cells. The journal of histochemistry and cytochemistry : official journal of the Histochemistry Society 2 35876388
2021 Colorectal Carcinoma Growth Inhibition by Dietary Care Combined with Probiotic Intervention through Targeting NRP2 Expression. Doklady. Biochemistry and biophysics 2 34697743
2025 Differential expression of viral entry protein neuropilin 1 (NRP1) and neuropilin 2 (NRP2) in fatal COVID-19. Journal of virology 1 41159753
2025 Hypoxic migrasomes drive colorectal cancer liver metastasis by mediating CD5L+ macrophage efferocytosis via NRP2/PROX1 axis. Journal of translational medicine 1 41361466
2024 The SEMA3F-NRP1/NRP2 axis is a key factor in the acquisition of invasive traits in in situ breast ductal carcinoma. Breast cancer research : BCR 1 39138514
2023 CircPI4KA Overexpression Enhances Carcinogenesis and Glycolysis Metabolism in Papillary Thyroid Carcinoma by Causing the miR-1287-5p-Mediated NRP2 Expression Elevation. Hormone and metabolic research = Hormon- und Stoffwechselforschung = Hormones et metabolisme 1 37813099
2026 Knockout of key receptors (PDGFRA and NRP2) in the guinea pig model blocks direct and endocytic pathways of CMV cell entry. The Journal of general virology 0 41805587
2026 The brain imaging feature-related gene NRP2 drives the malignant progression of glioblastoma through the FAK pathway: a Mendelian randomization study. Translational oncology 0 41861662
2026 Response to: "Re-examining interneuron-specific Nrp2 deletion: overlooked striatal and cortical contributions". Molecular psychiatry 0 41974886
2025 NRP2+ human mesenchymal stem cells have stemness-associated properties. Inflammation and regeneration 0 40289176
2025 BMSC-EVs improve post-stroke cognition by promoting regionally distinct synaptic repair via Sema3G-Nrp2/PlexinA4 Signaling. Experimental neurology 0 41270983
2025 A bispecific antibody designed to act as a NRP2/PLXNA1 agonist mimics anticancer activity of SEMA3F. The Journal of biological chemistry 0 41391772
2025 Neuropilin-2 (NRP2) mediates sorafenib resistance in clear cell renal cell carcinoma via the NRP2/NF-κB/TNFα axis. American journal of cancer research 0 41395296