EPHB2 EPH receptor B2 [Homo sapiens (human)] - Gene

Summary

Official Symbol: EPHB2provided by HGNC
Official Full Name: EPH receptor B2provided by HGNC
Primary source: HGNC:HGNC:3393
See related: Ensembl:ENSG00000133216 MIM:600997
Gene type: protein coding
RefSeq status: REVIEWED
Organism: Homo sapiens
Lineage: Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo
Also known as: DRT; EK5; ERK; CAPB; Hek5; PCBC; EPHT3; Tyro5; BDPLT22
Summary: 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]
Expression: Broad expression in colon (RPKM 7.3), small intestine (RPKM 5.2) and 17 other tissues See more
Orthologs: mouse all
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Genomic context

Location:: 1p36.12

Exon count:: 17

Annotation release	Status	Assembly	Chr	Location
109.20201120	current	GRCh38.p13 (GCF_000001405.39)	1	NC_000001.11 (22710770..22921500)
105	previous assembly	GRCh37.p13 (GCF_000001405.25)	1	NC_000001.10 (23037263..23241823)

Chromosome 1 - NC_000001.11 Genomic Context describing neighboring genes

Genomic regions, transcripts, and products

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Go to reference sequence details

Genomic Sequence:

Go to nucleotide: Graphics FASTA GenBank

Expression

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See details

Project title: HPA RNA-seq normal tissues
Description: RNA-seq was performed of tissue samples from 95 human individuals representing 27 different tissues in order to determine tissue-specificity of all protein-coding genes
BioProject: PRJEB4337
Publication: PMID 24309898
Analysis date: Wed Apr 4 07:08:55 2018

Bibliography

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GeneRIFs: Gene References Into Functions

What's a GeneRIF?

The Shb scaffold binds the Nck adaptor protein, p120 RasGAP, and Chimaerins and thereby facilitates heterotypic cell segregation by the receptor EphB2.
Title: The Shb scaffold binds the Nck adaptor protein, p120 RasGAP, and Chimaerins and thereby facilitates heterotypic cell segregation by the receptor EphB2.
Ephrin Receptor B2 Expression May Be a Prognostic Marker for Patients With Cancer: A Meta-analysis.
Title: Ephrin Receptor B2 Expression May Be a Prognostic Marker for Patients With Cancer: A Meta-analysis.
QYHJ could effectivly enhance the antihuman pancreatic tumor activity of GEM, which may be through inhibiting pancreatic cancer stem cell differentiation by lncRNA AB209630/miR-373/EphB2-NANOG signaling pathway.
Title: Qingyihuaji formula reverses gemcitabine resistant human pancreatic cancer through regulate lncRNA AB209630/miR-373/EphB2-NANOG signals.
DBS is activated by EPHB2/SRC signaling-mediated tyrosine phosphorylation in HEK293 cells.
Title: DBS is activated by EPHB2/SRC signaling-mediated tyrosine phosphorylation in HEK293 cells.
This study supports the hypothesis that EphB2 promotes liver fibrosis partly via activation of hepatic stellate cells.
Title: EphB2 receptor tyrosine kinase promotes hepatic fibrogenesis in mice via activation of hepatic stellate cells.
EphB2 regulates the actions of filopodia through a combination of precise subcellular localization and induction of specific intracellular signals within filopodia. Simple differences in the kinetics of EphB kinase signaling at the tips of filopodia mediate the choice between retraction and synaptogenesis.
Title: Filopodia Conduct Target Selection in Cortical Neurons Using Differences in Signal Kinetics of a Single Kinase.
The p.R745C variant within the EPHB2 tyrosine kinase domain was associated with defects in platelet aggregation, alphaIIbbeta3 activation, and granule secretion induced by G-protein-coupled receptor (GPCR) agonists and convulxin, as well as in thrombus formation on collagen under flow.
Title: A mutation of the human <i>EPHB2</i> gene leads to a major platelet functional defect.
The data further showed that mitochondrial fission significantly promoted the reprogramming of focal-adhesion dynamics and lamellipodia formation in hepatocellular carcinoma cells mainly by activating typical Ca(2+) /CaMKII/ERK/FAK pathway.
Title: Mitochondrial fission promotes cell migration by Ca<sup>2+</sup> /CaMKII/ERK/FAK pathway in hepatocellular carcinoma.
These findings suggested that miR-204 might serve as a tumor suppressor in the development of cervical cancer by directly targeting EphB2.
Title: miR-204 Regulates Cell Proliferation and Invasion by Targeting EphB2 in Human Cervical Cancer.
EphB2 signaling-mediated Sirt3 expression reduces MSC senescence by maintaining mitochondrial reactive oxygen species homeostasis.
Title: EphB2 signaling-mediated Sirt3 expression reduces MSC senescence by maintaining mitochondrial ROS homeostasis.

Submit: New GeneRIF Correction See all GeneRIFs (81)

Phenotypes

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Find tests for this gene in the NIH Genetic Testing Registry (GTR)

Review eQTL and phenotype association data in this region using PheGenI

Associated conditions

Description	Tests
BLEEDING DISORDER, PLATELET-TYPE, 22 MedGen: C5193111 OMIM: 618462 GeneReviews: Not available	not available
Prostate cancer/brain cancer susceptibility MedGen: C1863600 OMIM: 603688 GeneReviews: Not available	Compare labs

Variation

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See variants in ClinVar

See studies and variants in dbVar

See Variation Viewer (GRCh37.p13)

See Variation Viewer (GRCh38)

HIV-1 interactions

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Protein interactions

Protein	Gene	Interaction	Pubs
Envelope transmembrane glycoprotein gp41	env	A synthetic peptide corresponding to the immunosuppressive domain (amino acids 574-592) of HIV-1 gp41 downregulates the expression of EPH receptor B2 (EPHB2) in peptide-treated PBMCs	PubMed
Nef	nef	HIV-1 Nef rapidly terminates ERK activation in the presence of TPA in a macrophage-inducing system	PubMed

Go to the HIV-1, Human Interaction Database

Interactions

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Products	Interactant	Other Gene	Complex	Source	Pubs	Description

General gene information

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Markers

D1S407 (e-PCR)
- UniSTS:72197

GDB:593997 (e-PCR)
- UniSTS:157983

MARC_17495-17496:1030378704:1 (e-PCR)
- UniSTS:268320

D1S1353 (e-PCR)
- UniSTS:149549

GDB:636068 (e-PCR)
- UniSTS:158519

SHGC-8111 (e-PCR)
- UniSTS:3668

L18018 (e-PCR)
- UniSTS:8296

D1S1477 (e-PCR)
- UniSTS:149673

D1S3214 (e-PCR)
- UniSTS:39105

EPHB2_1768 (e-PCR)
- UniSTS:277212

SHGC-145465 (e-PCR)
- UniSTS:174591

Homology

Homologs of the EPHB2 gene: The EPHB2 gene is conserved in chimpanzee, dog, cow, mouse, rat, chicken, and zebrafish.
Orthologs from Annotation Pipeline: 237 organisms have orthologs with human gene EPHB2
Orthologs

Gene Ontology Provided by GOA

Function	Evidence Code	Pubs
ATP binding	IEA Inferred from Electronic Annotation more info
amyloid-beta binding	ISS Inferred from Sequence or Structural Similarity more info
amyloid-beta binding	TAS Traceable Author Statement more info	PubMed
axon guidance receptor activity	IEA Inferred from Electronic Annotation more info
identical protein binding	IEA Inferred from Electronic Annotation more info
protein binding	IPI Inferred from Physical Interaction more info	PubMed
protein tyrosine kinase activity	ISS Inferred from Sequence or Structural Similarity more info
protein-containing complex binding	ISS Inferred from Sequence or Structural Similarity more info
signaling receptor binding	IEA Inferred from Electronic Annotation more info
transmembrane receptor protein tyrosine kinase activity	IBA Inferred from Biological aspect of Ancestor more info	PubMed
transmembrane-ephrin receptor activity	IBA Inferred from Biological aspect of Ancestor more info	PubMed
transmembrane-ephrin receptor activity	ISS Inferred from Sequence or Structural Similarity more info
transmembrane-ephrin receptor activity	TAS Traceable Author Statement more info	PubMed

Process	Evidence Code	Pubs
angiogenesis	ISS Inferred from Sequence or Structural Similarity more info
axon guidance	IBA Inferred from Biological aspect of Ancestor more info	PubMed
axon guidance	ISS Inferred from Sequence or Structural Similarity more info
axonal fasciculation	ISS Inferred from Sequence or Structural Similarity more info
camera-type eye morphogenesis	IEA Inferred from Electronic Annotation more info
central nervous system projection neuron axonogenesis	IBA Inferred from Biological aspect of Ancestor more info	PubMed
commissural neuron axon guidance	ISS Inferred from Sequence or Structural Similarity more info
corpus callosum development	ISS Inferred from Sequence or Structural Similarity more info
dendritic spine development	ISS Inferred from Sequence or Structural Similarity more info
dendritic spine morphogenesis	ISS Inferred from Sequence or Structural Similarity more info
ephrin receptor signaling pathway	ISS Inferred from Sequence or Structural Similarity more info
ephrin receptor signaling pathway	TAS Traceable Author Statement more info
inactivation of MAPKK activity	ISS Inferred from Sequence or Structural Similarity more info
inner ear morphogenesis	ISS Inferred from Sequence or Structural Similarity more info
learning	ISS Inferred from Sequence or Structural Similarity more info
learning or memory	ISS Inferred from Sequence or Structural Similarity more info
multicellular organism development	IBA Inferred from Biological aspect of Ancestor more info	PubMed
negative regulation of ERK1 and ERK2 cascade	ISS Inferred from Sequence or Structural Similarity more info
negative regulation of NMDA glutamate receptor activity	ISS Inferred from Sequence or Structural Similarity more info
negative regulation of Ras protein signal transduction	ISS Inferred from Sequence or Structural Similarity more info
negative regulation of axonogenesis	IEA Inferred from Electronic Annotation more info
negative regulation of protein phosphorylation	ISS Inferred from Sequence or Structural Similarity more info
nervous system development	TAS Traceable Author Statement more info	PubMed
neuron projection retraction	IEA Inferred from Electronic Annotation more info
optic nerve morphogenesis	IEA Inferred from Electronic Annotation more info
peptidyl-tyrosine phosphorylation	ISS Inferred from Sequence or Structural Similarity more info
phosphorylation	ISS Inferred from Sequence or Structural Similarity more info
positive regulation of NMDA glutamate receptor activity	ISS Inferred from Sequence or Structural Similarity more info
positive regulation of gene expression	ISS Inferred from Sequence or Structural Similarity more info
positive regulation of kinase activity	IBA Inferred from Biological aspect of Ancestor more info	PubMed
positive regulation of long-term neuronal synaptic plasticity	IEA Inferred from Electronic Annotation more info
positive regulation of long-term synaptic potentiation	ISS Inferred from Sequence or Structural Similarity more info
positive regulation of protein localization to plasma membrane	ISS Inferred from Sequence or Structural Similarity more info
positive regulation of synapse assembly	ISS Inferred from Sequence or Structural Similarity more info
positive regulation of synaptic plasticity	ISS Inferred from Sequence or Structural Similarity more info
postsynaptic membrane assembly	IEA Inferred from Electronic Annotation more info
regulation of blood coagulation	IMP Inferred from Mutant Phenotype more info	PubMed
regulation of body fluid levels	ISS Inferred from Sequence or Structural Similarity more info
regulation of neuronal synaptic plasticity	ISS Inferred from Sequence or Structural Similarity more info
retinal ganglion cell axon guidance	IEA Inferred from Electronic Annotation more info
roof of mouth development	ISS Inferred from Sequence or Structural Similarity more info
trans-synaptic signaling by trans-synaptic complex, modulating synaptic transmission	IEA Inferred from Electronic Annotation more info
transmembrane receptor protein tyrosine kinase signaling pathway	IBA Inferred from Biological aspect of Ancestor more info	PubMed
urogenital system development	ISS Inferred from Sequence or Structural Similarity more info

Component	Evidence Code	Pubs
axon	ISS Inferred from Sequence or Structural Similarity more info
cytosol	TAS Traceable Author Statement more info
dendrite	ISS Inferred from Sequence or Structural Similarity more info
extracellular region	TAS Traceable Author Statement more info
glutamatergic synapse	IEA Inferred from Electronic Annotation more info
integral component of plasma membrane	IBA Inferred from Biological aspect of Ancestor more info	PubMed
integral component of plasma membrane	ISS Inferred from Sequence or Structural Similarity more info
integral component of postsynaptic membrane	IEA Inferred from Electronic Annotation more info
integral component of presynaptic membrane	IEA Inferred from Electronic Annotation more info
neuron projection	IBA Inferred from Biological aspect of Ancestor more info	PubMed
neuronal cell body	IEA Inferred from Electronic Annotation more info
nucleoplasm	IDA Inferred from Direct Assay more info
plasma membrane	IDA Inferred from Direct Assay more info
plasma membrane	TAS Traceable Author Statement more info
postsynapse	TAS Traceable Author Statement more info	PubMed
receptor complex	IBA Inferred from Biological aspect of Ancestor more info	PubMed

General protein information

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Preferred Names: ephrin type-B receptor 2

Names: EPH-like kinase 5; developmentally-regulated Eph-related tyrosine kinase; elk-related tyrosine kinase; eph tyrosine kinase 3; protein-tyrosine kinase HEK5; renal carcinoma antigen NY-REN-47; tyrosine-protein kinase TYRO5; tyrosine-protein kinase receptor EPH-3

NP_001296121.1

EC 2.7.10.1

NP_001296122.1

EC 2.7.10.1

NP_004433.2

EC 2.7.10.1

NP_059145.2

EC 2.7.10.1

XP_006710504.1

EC 2.7.10.1

XP_006710505.1

EC 2.7.10.1

XP_024309663.1

EC 2.7.10.1

NCBI Reference Sequences (RefSeq)

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RefSeqs maintained independently of Annotated Genomes

These reference sequences exist independently of genome builds. Explain

These reference sequences are curated independently of the genome annotation cycle, so their versions may not match the RefSeq versions in the current genome build. Identify version mismatches by comparing the version of the RefSeq in this section to the one reported in Genomic regions, transcripts, and products above.

Genomic

NG_011804.2 RefSeqGene

Range

5001..215663

Download

GenBank, FASTA, Sequence Viewer (Graphics), LRG_780

mRNA and Protein(s)

NM_001309192.2 → NP_001296121.1 ephrin type-B receptor 2 isoform 3 precursor

Status: REVIEWED

Description

Transcript Variant: This variant (3) lacks two in-frame exons in the 3' coding region compared to variant 2. It encodes isoform 3, which is shorter than isoform 2.

Source sequence(s)

AL035704, AL158086, AL512444

UniProtKB/TrEMBL

B4DSE0, Q4LE53, Q6NVW1

Conserved Domains (5) summary

cd05065
Location:558 → 826

PTKc_EphR_B; Catalytic domain of the Protein Tyrosine Kinases, Class EphB Ephrin Receptors

cd09552
Location:852 → 922

SAM_EPH-B2; SAM domain of EPH-B2 subfamily of tyrosine kinase receptors

cd10477
Location:19 → 196

EphR_LBD_B2; Ligand Binding Domain of Ephrin type-B Receptor 2

pfam00041
Location:437 → 519

fn3; Fibronectin type III domain

pfam14575
Location:500 → 558

EphA2_TM; Ephrin type-A receptor 2 transmembrane domain
NM_001309193.2 → NP_001296122.1 ephrin type-B receptor 2 isoform 4 precursor

See identical proteins and their annotated locations for NP_001296122.1

Status: REVIEWED

Description

Transcript Variant: This variant (4) uses an alternate in-frame splice site at an internal exon and alternate splice sites in the 3' coding region and 3' UTR, which results in a longer and novel 3' coding region compared to variant 2. It encodes isoform 4, which is longer than and has a distinct C-terminus compared to isoform 2.

Source sequence(s)

AL035704, AL158086, AL512444

Consensus CDS

CCDS81279.1

UniProtKB/Swiss-Prot

P29323

UniProtKB/TrEMBL

Q4LE53, Q6NVW1

Related

ENSP00000383053.3, ENST00000400191.7

Conserved Domains (7) summary

cd05065
Location:616 → 884

PTKc_EphR_B; Catalytic domain of the Protein Tyrosine Kinases, Class EphB Ephrin Receptors

cd09552
Location:910 → 980

SAM_EPH-B2; SAM domain of EPH-B2 subfamily of tyrosine kinase receptors

smart00454
Location:910 → 977

SAM; Sterile alpha motif

cd10477
Location:19 → 196

EphR_LBD_B2; Ligand Binding Domain of Ephrin type-B Receptor 2

pfam00041
Location:437 → 520

fn3; Fibronectin type III domain

pfam07714
Location:621 → 880

Pkinase_Tyr; Protein tyrosine kinase

pfam14575
Location:548 → 616

EphA2_TM; Ephrin type-A receptor 2 transmembrane domain
NM_004442.7 → NP_004433.2 ephrin type-B receptor 2 isoform 2 precursor

See identical proteins and their annotated locations for NP_004433.2

Status: REVIEWED

Description

Transcript Variant: This variant (2) represents the longest transcript. It encodes isoform 2.

Source sequence(s)

AK025975, AL035704, BC067861, DB282024, L41939

Consensus CDS

CCDS230.1

UniProtKB/Swiss-Prot

P29323

UniProtKB/TrEMBL

Q6NVW1

Related

ENSP00000363763.3, ENST00000374632.7

Conserved Domains (5) summary

cd05065
Location:617 → 885

PTKc_EphR_B; Catalytic domain of the Protein Tyrosine Kinases, Class EphB Ephrin Receptors

cd09552
Location:911 → 981

SAM_EPH-B2; SAM domain of EPH-B2 subfamily of tyrosine kinase receptors

cd10477
Location:19 → 196

EphR_LBD_B2; Ligand Binding Domain of Ephrin type-B Receptor 2

pfam00041
Location:437 → 519

fn3; Fibronectin type III domain

pfam14575
Location:548 → 617

EphA2_TM; Ephrin type-A receptor 2 transmembrane domain
NM_017449.5 → NP_059145.2 ephrin type-B receptor 2 isoform 1 precursor

See identical proteins and their annotated locations for NP_059145.2

Status: REVIEWED

Description

Transcript Variant: This variant (1) uses an alternate in-frame splice site compared to variant 2. It encodes isoform 1, which is shorter than isoform 2.

Source sequence(s)

AL035704, AL158086, AL512444

Consensus CDS

CCDS229.2

UniProtKB/Swiss-Prot

P29323

UniProtKB/TrEMBL

Q4LE53, Q6NVW1

Related

ENSP00000363761.3, ENST00000374630.7

Conserved Domains (5) summary

cd05065
Location:616 → 884

PTKc_EphR_B; Catalytic domain of the Protein Tyrosine Kinases, Class EphB Ephrin Receptors

cd09552
Location:910 → 980

SAM_EPH-B2; SAM domain of EPH-B2 subfamily of tyrosine kinase receptors

cd10477
Location:19 → 196

EphR_LBD_B2; Ligand Binding Domain of Ephrin type-B Receptor 2

pfam00041
Location:437 → 519

fn3; Fibronectin type III domain

pfam14575
Location:548 → 616

EphA2_TM; Ephrin type-A receptor 2 transmembrane domain

RefSeqs of Annotated Genomes: Homo sapiens Updated Annotation Release 109.20201120

The following sections contain reference sequences that belong to a specific genome build. Explain

Reference GRCh38.p13 Primary Assembly

Genomic

NC_000001.11 Reference GRCh38.p13 Primary Assembly

Range

22710770..22921500

Download

GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

XM_006710442.4 → XP_006710505.1 ephrin type-B receptor 2 isoform X2

Conserved Domains (7) summary

cd05065
Location:586 → 854

PTKc_EphR_B; Catalytic domain of the Protein Tyrosine Kinases, Class EphB Ephrin Receptors

cd09552
Location:880 → 950

SAM_EPH-B2; SAM domain of EPH-B2 subfamily of tyrosine kinase receptors

smart00454
Location:880 → 947

SAM; Sterile alpha motif

cd10477
Location:19 → 196

EphR_LBD_B2; Ligand Binding Domain of Ephrin type-B Receptor 2

pfam00041
Location:326 → 421

fn3; Fibronectin type III domain

pfam07714
Location:591 → 850

Pkinase_Tyr; Protein tyrosine kinase

pfam14575
Location:517 → 586

EphA2_TM; Ephrin type-A receptor 2 transmembrane domain
XM_006710441.4 → XP_006710504.1 ephrin type-B receptor 2 isoform X1

Related

ENSP00000363758.1, ENST00000374627.1

Conserved Domains (7) summary

cd05065
Location:610 → 878

PTKc_EphR_B; Catalytic domain of the Protein Tyrosine Kinases, Class EphB Ephrin Receptors

cd09552
Location:904 → 974

SAM_EPH-B2; SAM domain of EPH-B2 subfamily of tyrosine kinase receptors

smart00454
Location:904 → 971

SAM; Sterile alpha motif

cd10477
Location:12 → 189

EphR_LBD_B2; Ligand Binding Domain of Ephrin type-B Receptor 2

pfam00041
Location:430 → 513

fn3; Fibronectin type III domain

pfam07714
Location:615 → 874

Pkinase_Tyr; Protein tyrosine kinase

pfam14575
Location:541 → 610

EphA2_TM; Ephrin type-A receptor 2 transmembrane domain
XM_024453895.1 → XP_024309663.1 ephrin type-B receptor 2 isoform X3

Conserved Domains (4) summary

cd05065
Location:175 → 443

PTKc_EphR_B; Catalytic domain of the Protein Tyrosine Kinases, Class EphB Ephrin Receptors

cd09552
Location:469 → 539

SAM_EPH-B2; SAM domain of EPH-B2 subfamily of tyrosine kinase receptors

pfam00041
Location:1 → 78

fn3; Fibronectin type III domain

pfam14575
Location:107 → 175

EphA2_TM; Ephrin type-A receptor 2 transmembrane domain