Ephrin type-B receptor 2

Function

Receptor tyrosine kinase which binds promiscuously transmembrane ephrin-B family ligands residing on adjacent cells, leading to contact-dependent bidirectional signaling into neighboring cells. The signaling pathway downstream of the receptor is referred to as forward signaling while the signaling pathway downstream of the ephrin ligand is referred to as reverse signaling. Functions in axon guidance during development. Involved in the guidance of commissural axons, that form a major interhemispheric connection between the 2 temporal lobes of the cerebral cortex. Also involved in guidance of contralateral inner ear efferent growth cones at the midline and of retinal ganglion cell axons to the optic disk. In addition to axon guidance, also regulates dendritic spines development and maturation and stimulates the formation of excitatory synapses. Upon activation by EFNB1, abolishes the ARHGEF15-mediated negative regulation on excitatory synapse formation. Controls other aspects of development including angiogenesis, palate development and in inner ear development through regulation of endolymph production. Forward and reverse signaling through the EFNB2/EPHB2 complex regulate movement and adhesion of cells that tubularize the urethra and septate the cloaca. May function as a tumor suppressor. May be involved in the regulation of platelet activation and blood coagulation.

Classification

Family (Pfam)

PF14575 EphA2_TM, PF25599 Ephrin_CRD, PF01404 Ephrin_lbd, PF07699 Ephrin_rec_like, PF00041 fn3, PF07714 PK_Tyr_Ser-Thr, PF00536 SAM_1

InterPro

Eph_TM, EphB2_rcpt_lig-bd, Ephrin_rcpt_lig-bd_dom, Ephrin_rcpt_TKs, FN3_dom, FN3_sf, Galactose-bd-like_sf, Growth_fac_rcpt_cys_sf, Ig-like_fold, Kinase-like_dom_sf, Prot_kinase_dom, Protein_kinase_ATP_BS, SAM, SAM/pointed_sf, Ser-Thr/Tyr_kinase_cat_dom, Tyr-kin_ephrin_A/B_rcpt-like, Tyr_kinase_AS, Tyr_kinase_cat_dom, Tyr_kinase_ephrin_rcpt, Tyr_kinase_rcpt_V_CS

Functional cluster

Immunoglobulin-Domain Cell Adhesion Proteins

Experimental structures · PDB · 5

• 1B4F X-ray 1.95A
• 1F0M X-ray 2.20A
• 2QBX X-ray 2.30A
• 3ZFM X-ray 2.27A
• 8EBL X-ray 1.37A

A predicted model is available from AlphaFold.

Gene Ontology · 70

• GO:0030424 axon
• GO:0009986 cell surface
• GO:0005829 cytosol
• GO:0030425 dendrite
• GO:0043197 dendritic spine
• GO:0005576 extracellular region
• GO:0098978 glutamatergic synapse
• GO:0098686 hippocampal mossy fiber to CA3 synapse
• GO:0043025 neuronal cell body
• GO:0005886 plasma membrane
• GO:0098794 postsynapse
• GO:0045211 postsynaptic membrane
• GO:0042734 presynaptic membrane
• GO:0001540 amyloid-beta binding
• GO:0005524 ATP binding
• GO:0008046 axon guidance receptor activity
• GO:0042802 identical protein binding
• GO:0004713 protein tyrosine kinase activity
• GO:0044877 protein-containing complex binding
• GO:0005102 signaling receptor binding
• GO:0005005 transmembrane-ephrin receptor activity
• GO:0001525 angiogenesis
• GO:0007411 axon guidance
• GO:0007413 axonal fasciculation
• GO:0042113 B cell activation
• GO:1904646 cellular response to amyloid-beta
• GO:0071222 cellular response to lipopolysaccharide
• GO:0071679 commissural neuron axon guidance
• GO:0022038 corpus callosum development
• GO:0060996 dendritic spine development
• GO:0060997 dendritic spine morphogenesis
• GO:0048013 ephrin receptor signaling pathway
• GO:0021934 hindbrain tangential cell migration
• GO:0042472 inner ear morphogenesis
• GO:0007612 learning
• GO:0007611 learning or memory
• GO:0007162 negative regulation of cell adhesion
• GO:1900016 negative regulation of cytokine production involved in inflammatory response
• GO:0070373 negative regulation of ERK1 and ERK2 cascade
• GO:1900450 negative regulation of glutamate receptor signaling pathway
• GO:0046580 negative regulation of Ras protein signal transduction
• GO:0007399 nervous system development
• GO:1990535 neuron projection maintenance
• GO:0106028 neuron projection retraction
• GO:0018108 peptidyl-tyrosine phosphorylation
• GO:0016310 phosphorylation
• GO:0030890 positive regulation of B cell proliferation
• GO:0030335 positive regulation of cell migration
• GO:0061003 positive regulation of dendritic spine morphogenesis
• GO:0010628 positive regulation of gene expression
• GO:1900451 positive regulation of glutamate receptor signaling pathway
• GO:0002639 positive regulation of immunoglobulin production
• GO:1900273 positive regulation of long-term synaptic potentiation
• GO:2000010 positive regulation of protein localization to cell surface
• GO:1903078 positive regulation of protein localization to plasma membrane
• GO:0051965 positive regulation of synapse assembly
• GO:0031915 positive regulation of synaptic plasticity
• GO:0032760 positive regulation of tumor necrosis factor production
• GO:0097104 postsynaptic membrane assembly
• GO:2000822 regulation of behavioral fear response
• GO:0030193 regulation of blood coagulation
• GO:0050878 regulation of body fluid levels
• GO:0051489 regulation of filopodium assembly
• GO:0048168 regulation of neuronal synaptic plasticity
• GO:0046425 regulation of receptor signaling pathway via JAK-STAT
• GO:2000316 regulation of T-helper 17 type immune response
• GO:0060021 roof of mouth development
• GO:0120192 tight junction assembly
• GO:0001655 urogenital system development
• GO:0110077 vesicle-mediated intercellular transport

Disease associations

• prostate cancer, hereditary MONDO:0700275
• prostate cancer/brain cancer susceptibility MONDO:0011361
• bleeding disorder, platelet-type, 22 MONDO:0032765

Drugs targeting this protein · 1

• VANDETANIB inhibitor

Related proteins · sequence + function similarity

• Ephrin type-B receptor 2 1.00
• Ephrin type-B receptor 2 0.99
• Ephrin type-B receptor 2 0.99
• Ephrin type-B receptor 1 0.98
• Ephrin type-B receptor 1 0.98
• Ephrin type-B receptor 1 0.98
• Ephrin type-B receptor 3 0.97
• Ephrin type-B receptor 1-B 0.97
• Ephrin type-B receptor 1-A 0.96
• Ephrin type-B receptor 3 0.96
• Ephrin type-A receptor 7 0.96
• Ephrin type-A receptor 4 0.96

Co-cited proteins · studied together in the literature

• Ephrin type-A receptor 8 1 shared papers
• Ephrin type-A receptor 7 2 shared papers
• Ephrin type-B receptor 3 2 shared papers
• Ephrin type-A receptor 5 2 shared papers
• Ephrin type-A receptor 8 2 shared papers
• E3 ubiquitin-protein ligase RNF186 1 shared papers
• Ephrin type-A receptor 4 2 shared papers
• E3 ubiquitin-protein ligase RNF186 1 shared papers
• Serine protease HtrA 1 shared papers
• Kelch domain-containing protein 3 1 shared papers
• SPRY domain-containing SOCS box protein 1 1 shared papers
• SPRY domain-containing SOCS box protein 4 1 shared papers

Literature · 22 cited papers

• E3 ligase autoinhibition by C-degron mimicry maintains C-degron substrate fidelity. Mol. Cell · 2023
• Identification of Desmoglein-2 as a novel target of Helicobacter pylori HtrA in epithelial cells. Cell Commun. Signal. · 2021
• RNF186 regulates EFNB1 (ephrin B1)-EPHB2-induced autophagy in the colonic epithelial cells for the maintenance of intestinal homeostasis. Autophagy · 2021
• A mutation of the human EPHB2 gene leads to a major platelet functional defect. Blood · 2018
• Ubiquitin ligase SPSB4 diminishes cell repulsive responses mediated by EphB2. Mol. Biol. Cell · 2017
• Large-scale proteomics analysis of the human kinome. Mol. Cell. Proteomics · 2009
• Kinase-selective enrichment enables quantitative phosphoproteomics of the kinome across the cell cycle. Mol. Cell · 2008
• Three-dimensional structure of the EphB2 receptor in complex with an antagonistic peptide reveals a novel mode of inhibition. J. Biol. Chem. · 2007
• Patterns of somatic mutation in human cancer genomes. Nature · 2007
• The DNA sequence and biological annotation of human chromosome 1. Nature · 2006
• A common nonsense mutation in EphB2 is associated with prostate cancer risk in African American men with a positive family history. J. Med. Genet. · 2006
• Nonsense-mediated decay microarray analysis identifies mutations of EPHB2 in human prostate cancer. Nat. Genet. · 2004
• … and 10 more in the literature graph