EPHB2

This gene encodes a member of the Eph receptor family of receptor tyrosine kinase transmembrane glycoproteins. These receptors are composed of an N-terminal glycosylated ligand-binding domain, a transmembrane region and an intracellular kinase domain. They bind ligands called ephrins and are involved in diverse cellular processes including motility, division, and differentiation. A distinguishing characteristic of Eph-ephrin signaling is that both receptors and ligands are competent to transduce a signaling cascade, resulting in bidirectional signaling. This protein belongs to a subgroup of the Eph receptors called EphB. Proteins of this subgroup are distinguished from other members of the family by sequence homology and preferential binding affinity for membrane-bound ephrin-B ligands. Allelic variants are associated with prostate and brain cancer susceptibility. Alternative splicing results in multiple transcript variants. [provided by RefSeq, May 2015]

EPH Receptor B2

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 (PubMed:30213874).

Angiogenesis Source: UniProtKB
Axonal fasciculation Source: UniProtKB
Axon guidance Source: UniProtKB
B cell activation Source: ARUK-UCL
Camera-type eye morphogenesis Source: Ensembl
Central nervous system projection neuron axonogenesis Source: GO_Central
Commissural neuron axon guidance Source: UniProtKB
Corpus callosum development Source: UniProtKB
Dendritic spine development Source: UniProtKB
Dendritic spine morphogenesis Source: UniProtKB
Ephrin receptor signaling pathway Source: UniProtKB
Inner ear morphogenesis Source: UniProtKB
Learning Source: ARUK-UCL
Learning or memory Source: ARUK-UCL
Negative regulation of axonogenesis Source: Ensembl
Negative regulation of cell adhesion Source: ARUK-UCL
Negative regulation of ERK1 and ERK2 cascade Source: ARUK-UCL
Negative regulation of NMDA glutamate receptor activity Source: ARUK-UCL
Negative regulation of protein kinase activity Source: ARUK-UCL
Negative regulation of protein phosphorylation Source: ARUK-UCL
Negative regulation of Ras protein signal transduction Source: ARUK-UCL
Nervous system development Source: UniProtKB
Neuron projection retraction Source: Ensembl
Optic nerve morphogenesis Source: Ensembl
Peptidyl-tyrosine phosphorylation Source: UniProtKB
Phosphorylation Source: UniProtKB
Positive regulation of B cell proliferation Source: ARUK-UCL
Positive regulation of cell migration Source: ARUK-UCL
Positive regulation of gene expression Source: ARUK-UCL
Positive regulation of immunoglobulin production Source: ARUK-UCL
Positive regulation of kinase activity Source: GO_Central
Positive regulation of long-term neuronal synaptic plasticity Source: Ensembl
Positive regulation of long-term synaptic potentiation Source: ARUK-UCL
Positive regulation of NMDA glutamate receptor activity Source: ARUK-UCL
Positive regulation of protein localization to plasma membrane Source: ARUK-UCL
Positive regulation of synapse assembly Source: UniProtKB
Positive regulation of synaptic plasticity Source: ARUK-UCL
Positive regulation of tumor necrosis factor production Source: ARUK-UCL
Postsynaptic membrane assembly Source: Ensembl
Regulation of blood coagulation Source: UniProtKB
Regulation of body fluid levels Source: UniProtKB
Regulation of neuronal synaptic plasticity Source: ARUK-UCL
Retinal ganglion cell axon guidance Source: Ensembl
Roof of mouth development Source: UniProtKB
Transmembrane receptor protein tyrosine kinase signaling pathway Source: GO_Central
Trans-synaptic signaling by trans-synaptic complex, modulating synaptic transmission Source: Ensembl
Urogenital system development Source: UniProtKB

Cell membrane; Axon; Dendrite

Prostate cancer (PC):
A malignancy originating in tissues of the prostate. Most prostate cancers are adenocarcinomas that develop in the acini of the prostatic ducts. Other rare histopathologic types of prostate cancer that occur in approximately 5% of patients include small cell carcinoma, mucinous carcinoma, prostatic ductal carcinoma, transitional cell carcinoma, squamous cell carcinoma, basal cell carcinoma, adenoid cystic carcinoma (basaloid), signet-ring cell carcinoma and neuroendocrine carcinoma.
Bleeding disorder, platelet-type, 22 (BDPLT22):
An autosomal recessive disorder characterized by increased bleeding tendency due to platelet dysfunction. Clinical features include epistaxis, hematomas, bleeding after minor injuries, and menorrhagia.

Extracellular: 19-543
Helical: 544-564
Cytoplasmic: 565-1055

Autophosphorylated; ligand binding stimulates autophosphorylation on tyrosine residues.By similarity
Polyubiquitinated; ligand binding stimulates ubiquitination.
Ligand binding induces cleavage by matrix metalloproteinases (MMPs) such as MMP7/MMP9, producing an EphB2/N-terminal fragment (NTF) and a C-terminal long fragment (EphB2-LF). EphB2-LF is further cleaved by MMPs, producing EphB2/CTF1 which is further cleaved by the PS1/gamma-secretase producing EphB2/CTF2.