EPHB2

Protein identityUniProt · HPA

UniProt accession

P29323

Gene

EPHB2

Ensembl

ENSG00000133216

Chromosome

1

Canonical length

1055 aa

Protein class

Cancer-related genes, Disease related genes, Enzymes, Human disease related genes, Plasma proteins, Potential drug targets, Predicted intracellular proteins, Predicted membrane proteins

Subcellular location

Nucleoplasm,Plasma membrane

Secretome location

Intracellular and membrane

OverviewNCBI Gene

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]

Canonical amino-acid sequenceUniProt

1055 residues, UniProt reviewed canonical sequence.

>P29323|EPHB2
     1  MALRRLGAAL LLLPLLAAVE ETLMDSTTAT AELGWMVHPP SGWEEVSGYD ENMNTIRTYQ
    61  VCNVFESSQN NWLRTKFIRR RGAHRIHVEM KFSVRDCSSI PSVPGSCKET FNLYYYEADF
   121  DSATKTFPNW MENPWVKVDT IAADESFSQV DLGGRVMKIN TEVRSFGPVS RSGFYLAFQD
   181  YGGCMSLIAV RVFYRKCPRI IQNGAIFQET LSGAESTSLV AARGSCIANA EEVDVPIKLY
   241  CNGDGEWLVP IGRCMCKAGF EAVENGTVCR GCPSGTFKAN QGDEACTHCP INSRTTSEGA
   301  TNCVCRNGYY RADLDPLDMP CTTIPSAPQA VISSVNETSL MLEWTPPRDS GGREDLVYNI
   361  ICKSCGSGRG ACTRCGDNVQ YAPRQLGLTE PRIYISDLLA HTQYTFEIQA VNGVTDQSPF
   421  SPQFASVNIT TNQAAPSAVS IMHQVSRTVD SITLSWSQPD QPNGVILDYE LQYYEKELSE
   481  YNATAIKSPT NTVTVQGLKA GAIYVFQVRA RTVAGYGRYS GKMYFQTMTE AEYQTSIQEK
   541  LPLIIGSSAA GLVFLIAVVV IAIVCNRRGF ERADSEYTDK LQHYTSGHMT PGMKIYIDPF
   601  TYEDPNEAVR EFAKEIDISC VKIEQVIGAG EFGEVCSGHL KLPGKREIFV AIKTLKSGYT
   661  EKQRRDFLSE ASIMGQFDHP NVIHLEGVVT KSTPVMIITE FMENGSLDSF LRQNDGQFTV
   721  IQLVGMLRGI AAGMKYLADM NYVHRDLAAR NILVNSNLVC KVSDFGLSRF LEDDTSDPTY
   781  TSALGGKIPI RWTAPEAIQY RKFTSASDVW SYGIVMWEVM SYGERPYWDM TNQDVINAIE
   841  QDYRLPPPMD CPSALHQLML DCWQKDRNHR PKFGQIVNTL DKMIRNPNSL KAMAPLSSGI
   901  NLPLLDRTIP DYTSFNTVDE WLEAIKMGQY KESFANAGFT SFDVVSQMMM EDILRVGVTL
   961  AGHQKKILNS IQVMRAQMNQ IQSVEGQPLA RRPRATGRTK RCQPRDVTKK TCNSNDGKKK
  1021  GMGKKKTDPG RGREIQGIFF KEDSHKESND CSCGG

LocalizationUniProt · AlphaFold · HPA

Whether an antibody against EPHB2 can act on the native protein depends on physical access: surface and secreted proteins are reachable by circulating antibodies, intracellular proteins usually are not.

Antibody reachability

Cell surface

Secreted

No

Transmembrane segments

1

Mean surface accessibility (rSASA)

0.34

Highest tissue expression

22 nTPM

Expression across tissuesHPA

DiseaseUniProt · ClinVar · IEDB · PubMed

Four sources answering four different questions about EPHB2.

Disease | AllUniProt

Conditions EPHB2 is implicated in, by any mechanism.

• Prostate cancer (PC) MIM:176807
• Bleeding disorder, platelet-type, 22 (BDPLT22) MIM:618462

Disease | GeneticClinVar

2 pathogenic / likely-pathogenic of 173 ClinVar records.

Conditions with pathogenic or likely-pathogenic variants.

• Prostate cancer/brain cancer susceptibility
• Bleeding disorder, platelet-type, 22

ReferencesPubMed · IEDB

Publications for EPHB2 from three distinct lines of evidence, kept separate because they answer different questions: whether antibodies are directed at the protein, whether a B-cell epitope has been mapped on it, and whether a T-cell epitope has. Each is labelled with its source.

Sources: PubMed — antigen-level antibody evidence from a custom retrieval. Records matching a controlled set of autoantibody terms (the MeSH descriptors Autoantibodies and Autoantigens, with title and abstract term variants) were obtained through NCBI E-utilities, and their titles and abstracts parsed for constructions that direct an antibody at a named protein rather than for co-occurrence. Captured names were resolved against UniProt nomenclature and each antigen adjudicated individually against the source text. IEDB — curated epitope assays from the Immune Epitope Database (Vita et al., Nucleic Acids Research 2019). Bibliographic records from PubMed and MeSH, U.S. National Library of Medicine; citation metrics from NIH iCite (Hutchins et al., PLoS Biology 2016). Titles link to PubMed; abstracts are not reproduced here. The NLM does not endorse this analysis.

Genetic constraint and essentialitygnomAD · DepMap

Does the body need this protein intact? Low LOEUF or a strong DepMap dependency means loss or blockade of the protein is likely to be felt.

gnomAD LOEUF (loss-of-function intolerance)

0.18

gnomAD pLI

1

gnomAD missense Z

2.45

DepMap mean gene effect

0.01

DepMap dependency class

none

Cancer expressionTCGA

Across TCGA tumor cohorts, this protein is over-expressed in roughly 4% of surveyed tumor types (aggregate summary; per-cohort expression, alteration, and survival load in the interactive view).

OntologyGO

Biological processes

• angiogenesis
• axon guidance
• axonal fasciculation
• B cell activation
• camera-type eye morphogenesis
• cellular response to amyloid-beta
• cellular response to lipopolysaccharide
• central nervous system projection neuron axonogenesis
• commissural neuron axon guidance
• corpus callosum development
• dendritic spine development
• dendritic spine morphogenesis
• ephrin receptor signaling pathway
• hindbrain tangential cell migration
• inner ear morphogenesis
• learning
• learning or memory
• negative regulation of axonogenesis
• negative regulation of cell adhesion
• negative regulation of cytokine production involved in inflammatory response
• negative regulation of ERK1 and ERK2 cascade
• negative regulation of glutamate receptor signaling pathway
• negative regulation of Ras protein signal transduction
• nervous system development
• neuron projection maintenance
• neuron projection retraction
• optic nerve morphogenesis
• peptidyl-tyrosine phosphorylation
• phosphorylation
• positive regulation of B cell proliferation
• positive regulation of cell migration
• positive regulation of dendritic spine morphogenesis
• positive regulation of gene expression
• positive regulation of glutamate receptor signaling pathway
• positive regulation of immunoglobulin production
• positive regulation of long-term neuronal synaptic plasticity
• positive regulation of long-term synaptic potentiation
• positive regulation of protein localization to cell surface
• positive regulation of protein localization to plasma membrane
• positive regulation of synapse assembly
• positive regulation of synaptic plasticity
• positive regulation of tumor necrosis factor production
• postsynaptic membrane assembly
• regulation of behavioral fear response
• regulation of blood coagulation
• regulation of body fluid levels
• regulation of filopodium assembly
• regulation of neuronal synaptic plasticity
• regulation of receptor signaling pathway via JAK-STAT
• retinal ganglion cell axon guidance
• roof of mouth development
• tight junction assembly
• urogenital system development
• vesicle-mediated intercellular transport
• regulation of T-helper 17 type immune response

Molecular functions

• amyloid-beta binding
• ATP binding
• axon guidance receptor activity
• identical protein binding
• protein tyrosine kinase activity
• protein-containing complex binding
• signaling receptor binding
• transmembrane-ephrin receptor activity

Cellular components

• axon
• cell surface
• cytosol
• dendrite
• dendritic spine
• extracellular region
• glutamatergic synapse
• hippocampal mossy fiber to CA3 synapse
• neuronal cell body
• nucleoplasm
• plasma membrane
• postsynapse
• postsynaptic membrane
• presynaptic membrane

Protein domainsUniProt · Pfam · InterPro

• Protein kinase domain
• Ephrin, ligand binding domain
• Serine-threonine/tyrosine-protein kinase, catalytic domain
• Tyrosine-protein kinase, receptor class V, conserved site
• Sterile alpha motif domain
• Fibronectin type III
• Tyrosine-protein kinase, active site
• Galactose-binding-like domain superfamily
• Growth factor receptor cysteine-rich domain superfamily
• Protein kinase-like domain superfamily
• Tyrosine-protein kinase ephrin type A/B receptor-like
• Sterile alpha motif/pointed domain superfamily
• Immunoglobulin-like fold
• Ephrin receptor type-A /type-B
• Protein kinase, ATP binding site
• Tyrosine-protein kinase, catalytic domain
• Ephrin, transmembrane domain
• Fibronectin type III superfamily
• Ephrin receptor tyrosine kinases
• Fibronectin type III domain
• SAM domain (Sterile alpha motif)
• Ephrin receptor ligand binding domain
• Tyrosine-protein kinase ephrin type A/B receptor-like
• Protein tyrosine and serine/threonine kinase
• Ephrin type-A receptor 2 transmembrane domain
• Ephrin cysteine rich domain
• Ephrin type-B receptor 2, ligand binding domain

KeywordsUniProt

• ATP-binding
• Cell membrane
• Cell projection
• Developmental protein
• Disulfide bond
• Glycoprotein
• Isopeptide bond
• Kinase
• Membrane
• Neurogenesis
• Nucleotide-binding
• Phosphoprotein
• Receptor
• Repeat
• Signal
• Transferase
• Transmembrane
• Transmembrane helix
• Tumor suppressor
• Tyrosine-protein kinase
• Ubl conjugation

InteractionsUniProt · HPA

Protein binding partners of EPHB2 in the human serome: UniProt-annotated complex subunits plus reported interactors. Each links to its own Seroatlas record.

• AQP1
• ARHGEF15
• EFNA5
• RASA1
• SH2D3C
• SPSB1
• SPSB4
• GRIP1
• CSF1R
• EPHA4
• EPHA7