Affinage

EFNB3

Ephrin-B3 · UniProt Q15768

Audit flag: rerun needed
Length
340 aa
Mass
35.8 kDa
Annotated
2026-04-28
50 papers in source corpus 14 papers cited in narrative 14 extracted findings

Mechanistic narrative

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Mechanism profile

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Evidence

Reading pass · 14 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2011 Ephrin-B3 (EFNB3) acts as an essential component of the Reelin signaling pathway for neuronal migration: Reelin binds directly to the extracellular domain of ephrin-Bs including EFNB3, which associate at the neuronal membrane with VLDLR and ApoER2 receptors; clustering of ephrin-Bs recruits and promotes phosphorylation of Dab1, which is required for Reelin signaling; loss of ephrin-B function severely impairs Reelin-induced Dab1 phosphorylation; activation of ephrin-Bs can rescue reeler neuronal migration defects in the absence of Reelin. Co-immunoprecipitation, genetic compound mutants (Reln+/-;Efnb3-/- mice), triple ephrin-B1/B2/B3 knockouts, rescue experiments, Dab1 phosphorylation assays Nature High 21460838
2016 EFNB3 knockout in female mice leads to increased blood pressure and augmented vascular smooth muscle cell (VSMC) contractility; EFNB3 deletion in VSMCs results in reduced myosin light chain kinase phosphorylation; estrogen augments VSMC contractility via a nongenomic GPER pathway while testosterone reduces it in the absence of EFNB3; these effects are absent in wild-type VSMCs, indicating EFNB3 normally buffers sex hormone effects on VSMC contractility. Efnb3 gene knockout mice, VSMC contractility assays, GPER knockdown assays, ovariectomy experiments, myosin light chain kinase phosphorylation assays American journal of physiology. Heart and circulatory physiology High 26851246
2016 GRIP1, a glutamate receptor interacting protein in the EFNB3 reverse signaling pathway, regulates VSMC contractility; siRNA knockdown of GRIP1 in mouse VSMCs increases contractility, and Efnb3 KO mice show enhanced carotid artery constriction by echocardiography. siRNA knockdown of GRIP1 in VSMCs, Efnb3 KO mouse echocardiography, in vitro contractility assays Scientific reports Medium 27941904
2003 Mouse EFNB3 expressed on T cells acts as a costimulatory ligand: solid-phase EFNB3-Fc in the presence of suboptimal anti-CD3 crosslinking enhances T-cell proliferation, activation marker expression, IFN-γ production, and cytotoxic T-cell activity; TCR and EFNB3 receptors co-congregate into lipid rafts upon crosslinking; EFNB3R costimulation augments p38 and p44/42 MAPK activation; the effect is insensitive to cyclosporin A, resembling CD28 costimulation. Solid-phase EFNB3-Fc stimulation assays, proliferation assays, cytokine measurements, lipid raft co-localization, MAPK activation assays, cyclosporin A pharmacological treatment The Journal of biological chemistry Medium 13679370
2008 Crystal structures of Nipah and Hendra virus attachment glycoproteins in complex with human EFNB2 revealed that EFNB3 (as analogous receptor) mediates viral attachment via an extensive protein-protein interface involving a crucial phenylalanine side chain on EFNB2/B3 that inserts into a hydrophobic pocket on the viral attachment protein; this is mechanistically distinct from sialic acid-based paramyxovirus attachment. X-ray crystallography of viral attachment glycoprotein–EFNB2 complex Nature structural & molecular biology High 18488039
2024 Structure-guided mutagenesis of NiV receptor-binding protein identified two regions (including residues N557 and Y581) critical for EFNB3 binding; NiV interaction with Y120 of EFNB3 is important for EFNB3 receptor usage; substitution of these residues severely impairs EFNB3-mediated entry by NiV pseudotyped viral particles. Structure-guided mutagenesis, EFNB3 binding assays, pseudotyped viral particle entry assays Journal of virology High 38426726
2016 Contrary to earlier claims, compound mutant Efnb3-/-;Reln+/- mice and triple Efnb1;2;3-/- mice do not show defects of cortical layering or elevated Dab1 levels, indicating that while protein-protein interactions between ephrin-Bs and Reelin have been confirmed, they do not affect the radial positioning of migrating neocortical pyramidal neurons. Efnb3-/-;Reln+/- compound mutants, triple Efnb1;2;3-/- knockout mice, cortical layering analysis, Dab1 protein level measurement Nature Medium 27882975
2021 Ephrin-B3/EphBs forward signaling in the spinal cord regulates nociception: Efnb3 knockout mice show increased thermal and mechanical thresholds and aberrant thin myelin sheaths; PLP (proteolipid protein) expression is reduced in the L4-6 spinal cord of Efnb3-/- mice; intrathecal PLP siRNA increases pain thresholds in wild-type mice; AAV9-PLP overexpression rescues pain hypersensitivity in Efnb3-/- mice; Efnb3lacz mice (forward signaling intact, reverse signaling absent) show normal pain behavior, indicating the reverse signaling is responsible. Efnb3-/- and Efnb3lacz conditional knock-in mice, behavioral pain assays, western blot, immunofluorescence, intrathecal siRNA, AAV9 gene delivery Fundamental & clinical pharmacology Medium 34904278
2022 Continuous activation of EFNB3 reverse signaling in benign prostate fibroblasts induces a cancer-associated fibroblast (CAF) phenotype and pro-tumorigenic secretome; this effect is mediated through Src family kinase (SFK) activation; SFK inhibition suppresses EFNB3-induced α-SMA and Tenascin-C expression in vitro. Stable EFNB3 overexpression in BHPrS1 cells, SFK inhibitor treatment, CAF marker expression assays, in vitro and in vivo tumorigenicity assays Cancers Medium 35565468
2023 Ephrin B3 promotes intestinal epithelial barrier dysfunction and inflammation in colitis via two pathways: (1) inactivation of the ITGB4/AKT signaling pathway promoting epithelial barrier dysfunction; (2) activation of the Gremlin-1/NF-κB signaling pathway increasing inflammatory factor release; Efnb3-/- mice showed reduced DSS-induced colitis and reduced susceptibility to colitis-associated colorectal cancer. Efnb3-/- mice, DSS-induced colitis model, AOM/DSS colorectal cancer model, label-free quantitative proteomics, western blotting Biochemical pharmacology Medium 38142837
2025 Ephrin B3 drives tumorigenesis in cutaneous squamous cell carcinoma via regulation of CK19 (cytokeratin 19), which in turn positively regulates the NOTCH1 signaling pathway; Efnb3 deficiency also mitigates inflammatory responses through the MAPK pathway in acute skin inflammation. Efnb3-/- mice in DMBA/TPA carcinogenesis model, EFNB3 knockdown in A431 cells, label-free proteomics, Reactome pathway analysis Medical oncology Medium 40711642
2019 LHX1 transcription factor regulates the expression of Eph/ephrin family guidance receptors including those responsive to ephrin-B3 in POA-derived cortical interneurons, thereby modulating their directional migration and layer distribution. Conditional LHX1 knockout in POA-derived interneurons, live imaging of interneuron migration, layer distribution analysis Cerebral cortex Low 29912395
1997 EFNB3 (originally designated EPLG8/LERK-8) was cloned and mapped to human chromosome 17p11.2-p13.1; it encodes a transmembrane protein related to ephrin-B2 and another B-class ephrin, expressed predominantly in brain and expressed at highest levels in forebrain subregions. cDNA library screening, chromosomal mapping by PCR of somatic cell hybrid panels, Northern blot tissue expression analysis Genomics Medium 9126477
2025 A frameshift variant (2-bp duplication, c.643_644dup) in EFNB3 causes autosomal recessive congenital mirror movement disorder in Weimaraner dogs, resembling the phenotype of Efnb3-/- knockout mice, establishing EFNB3 as necessary for normal spinal midline barrier formation during neurodevelopment. Linkage and autozygosity mapping, whole-genome sequencing of 3 affected and 1489 control dogs, pathological investigations Movement disorders Medium 40401490

Source papers

Stage 0 corpus · 50 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2008 Structural basis of Nipah and Hendra virus attachment to their cell-surface receptor ephrin-B2. Nature structural & molecular biology 197 18488039
2011 Ephrin Bs are essential components of the Reelin pathway to regulate neuronal migration. Nature 135 21460838
2016 Genome-wide DNA Methylation Changes in a Mouse Model of Infection-Mediated Neurodevelopmental Disorders. Biological psychiatry 121 27769567
2000 Implications of EPHB6, EFNB2, and EFNB3 expressions in human neuroblastoma. Proceedings of the National Academy of Sciences of the United States of America 86 10984508
1999 Coexpression of transcripts encoding EPHB receptor protein tyrosine kinases and their ephrin-B ligands in human small cell lung carcinoma. Clinical cancer research : an official journal of the American Association for Cancer Research 79 10037197
2011 Decreased expression of axon-guidance receptors in the anterior cingulate cortex in autism. Molecular autism 75 21859478
1999 High-level expression of EPHB6, EFNB2, and EFNB3 is associated with low tumor stage and high TrkA expression in human neuroblastomas. Clinical cancer research : an official journal of the American Association for Cancer Research 74 10389937
2010 De novo expression of EphA2 in osteosarcoma modulates activation of the mitogenic signalling pathway. Histopathology 58 21166698
2014 Transcriptional regulation by FOXP1, FOXP2, and FOXP4 dimerization. Journal of molecular neuroscience : MN 52 25027557
2003 Mouse ephrinB3 augments T-cell signaling and responses to T-cell receptor ligation. The Journal of biological chemistry 48 13679370
2019 Pituitary Transcriptomic Study Reveals the Differential Regulation of lncRNAs and mRNAs Related to Prolificacy in Different FecB Genotyping Sheep. Genes 46 30781725
2004 Favorable neuroblastoma genes and molecular therapeutics of neuroblastoma. Clinical cancer research : an official journal of the American Association for Cancer Research 46 15355914
2014 Identification of molecular pathways facilitating glioma cell invasion in situ. PloS one 40 25365423
2019 Sonic hedgehog pathway activation is associated with cetuximab resistance and EPHB3 receptor induction in colorectal cancer. Theranostics 34 31149041
2022 Runs of Homozygosity Revealed Reproductive Traits of Hu Sheep. Genes 32 36292733
2012 Cancer stem cells from a rare form of glioblastoma multiforme involving the neurogenic ventricular wall. Cancer cell international 24 22995409
2001 Association among EPHB2, TrkA, and MYCN expression in low-stage neuroblastomas. Medical and pediatric oncology 24 11464911
2012 790 Kb microduplication in chromosome band 17p13.1 associated with intellectual disability, afebrile seizures, dysmorphic features, diabetes, and hypothyroidism. European journal of medical genetics 20 22365944
2022 Ephrin B Activate Src Family Kinases in Fibroblasts Inducing Stromal Remodeling in Prostate Cancer. Cancers 17 35565468
2019 The Transcription Factor LHX1 Regulates the Survival and Directed Migration of POA-derived Cortical Interneurons. Cerebral cortex (New York, N.Y. : 1991) 17 29912395
2006 Comparative integromics on Ephrin family. Oncology reports 17 16596216
2016 Estrogen and testosterone in concert with EFNB3 regulate vascular smooth muscle cell contractility and blood pressure. American journal of physiology. Heart and circulatory physiology 16 26851246
2010 17p13.1 microdeletion involving the TP53 gene in a boy presenting with mental retardation but no tumor. American journal of medical genetics. Part A 16 20425836
2007 De novo identification of MIZ-1 (ZBTB17) encoding a MYC-interacting zinc-finger protein as a new favorable neuroblastoma gene. Clinical cancer research : an official journal of the American Association for Cancer Research 16 17947461
1997 cDNA cloning, chromosomal localization, and expression pattern of EPLG8, a new member of the EPLG gene family encoding ligands of EPH-related protein-tyrosine kinase receptors. Genomics 16 9126477
2013 Destabilization of MYC/MYCN by the mitochondrial inhibitors, metaiodobenzylguanidine, metformin and phenformin. International journal of molecular medicine 15 24190252
2009 High level MycN expression in non-MYCN amplified neuroblastoma is induced by the combination treatment nutlin-3 and doxorubicin and enhances chemosensitivity. Oncology reports 14 19885598
2016 The role of GRIP1 and ephrin B3 in blood pressure control and vascular smooth muscle cell contractility. Scientific reports 13 27941904
2016 Ephrin Bs and canonical Reelin signalling. Nature 12 27882975
2014 Neurodevelopmental delays and macrocephaly in 17p13.1 microduplication syndrome. American journal of medical genetics. Part A 12 25123844
2022 Glycoprotein attachment with host cell surface receptor ephrin B2 and B3 in mediating entry of nipah and hendra virus: a computational investigation. Journal of chemical sciences (Bangalore, India) 9 36465097
2017 Evidence from single nucleotide polymorphism analyses of ADVANCE study demonstrates EFNB3 as a hypertension risk gene. Scientific reports 8 28272517
2021 Investigation of Key Signaling Pathways Associating miR-204 and Common Retinopathies. BioMed research international 7 34646884
2020 Transcriptomic profile of Pea3 family members reveal regulatory codes for axon outgrowth and neuronal connection specificity. Scientific reports 7 33097800
2015 Genome-wide association pathway analysis to identify candidate single nucleotide polymorphisms and molecular pathways for gastric adenocarcinoma. Tumour biology : the journal of the International Society for Oncodevelopmental Biology and Medicine 6 25687184
2025 Interpretable machine learning-guided single-cell mapping deciphers multi-lineage pancreatic dysregulation in type 2 diabetes. Cardiovascular diabetology 4 40707916
2024 Structure-guided mutagenesis of Henipavirus receptor-binding proteins reveals molecular determinants of receptor usage and antibody-binding epitopes. Journal of virology 4 38426726
2023 Evaluation of the interaction between potent small molecules against the Nipah virus Glycoprotein in Malaysia and Bangladesh strains, accompanied by the human Ephrin-B2 and Ephrin-B3 receptors; a simulation approach. Molecular diversity 4 36808582
2018 Analysis of the association of EPHB6, EFNB1 and EFNB3 variants with hypertension risks in males with hypogonadism. Scientific reports 4 30262919
2025 The alternatively spliced diacylglycerol kinase gamma-Δ exon13 transcript generated under hypoxia promotes glioblastoma progression. Oncology research 3 40296900
2025 EFNB3 Frameshift Variant in Weimaraner Dogs with a Condition Resembling a Congenital Mirror Movement Disorder. Movement disorders : official journal of the Movement Disorder Society 3 40401490
2023 Integrated analysis of RNA-seq in hepatocellular carcinoma reveals competing endogenous RNA network composed of circRNA, lncRNA, and mRNA. Medicine 3 36827016
2023 Ephrin B3 exacerbates colitis and colitis-associated colorectal cancer. Biochemical pharmacology 2 38142837
2021 Activation of spinal ephrin-B3/EphBs signaling induces hyperalgesia through a PLP-mediated mechanism. Fundamental & clinical pharmacology 2 34904278
2026 Epigenetic mediators of diet and lifestyle and insulin resistance. Genes & nutrition 0 41580603
2026 In silico characterization of G protein-host receptor interactions in Bangladesh Nipah virus mutants toward therapeutic target identification. In silico pharmacology 0 41613644
2025 Ephrin B3 drives tumorigenesis and inflammation in cutaneous squamous cell carcinoma. Medical oncology (Northwood, London, England) 0 40711642
2025 Molecular Encoding of Ischemic Stroke and its Resolution after Human Neural Stem Cell Therapy by Extracellular Vesicles. MedComm 0 41164797
2025 Germline Variant Call Accuracy in Whole Genome Sequence Data from Canine Formalin-Fixed Paraffin-Embedded Tissue Samples. Genes 0 41300821
2023 Structure guided mutagenesis of Henipavirus Receptor Binding Proteins reveals molecular determinants of receptor usage and antibody binding epitopes. bioRxiv : the preprint server for biology 0 38045373