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; AllianceGenome:HGNC:3393
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
RS_2024_08	current	GRCh38.p14 (GCF_000001405.40)	1	NC_000001.11 (22710838..22921500)
RS_2024_08	current	T2T-CHM13v2.0 (GCF_009914755.1)	1	NC_060925.1 (22535722..22747006)
RS_2024_09	previous assembly	GRCh37.p13 (GCF_000001405.25)	1	NC_000001.10 (23037331..23247993)

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 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?

ephrin-B2 promotes nociceptive plasticity and hyperalgesic priming through EphB2-MNK-eIF4E signaling in both mice and humans.
Title: ephrin-B2 promotes nociceptive plasticity and hyperalgesic priming through EphB2-MNK-eIF4E signaling in both mice and humans.
EPHB2 as a key mediator of glioma progression: Insights from microenvironmental receptor ligand-related prognostic gene signature.
Title: EPHB2 as a key mediator of glioma progression: Insights from microenvironmental receptor ligand-related prognostic gene signature.
CXCL13 promotes TNF-alpha synthesis in rheumatoid arthritis through activating ERK/p38 pathway and inhibiting miR-330-3p generation.
Title: CXCL13 promotes TNF-α synthesis in rheumatoid arthritis through activating ERK/p38 pathway and inhibiting miR-330-3p generation.
Ubiquitin ligase and signalling hub MYCBP2 is required for efficient EPHB2 tyrosine kinase receptor function.
Title: Ubiquitin ligase and signalling hub MYCBP2 is required for efficient EPHB2 tyrosine kinase receptor function.
LINC00488 Induces Tumorigenicity in Retinoblastoma by Regulating microRNA-30a-5p/EPHB2 Axis.
Title: LINC00488 Induces Tumorigenicity in Retinoblastoma by Regulating microRNA-30a-5p/EPHB2 Axis.
EphrinB2/ephB2 activation facilitates colonic synaptic potentiation and plasticity contributing to long-term visceral hypersensitivity in irritable bowel syndrome.
Title: EphrinB2/ephB2 activation facilitates colonic synaptic potentiation and plasticity contributing to long-term visceral hypersensitivity in irritable bowel syndrome.
EphB2 activates CREB-dependent expression of Annexin A1 to regulate dendritic spine morphogenesis.
Title: EphB2 activates CREB-dependent expression of Annexin A1 to regulate dendritic spine morphogenesis.
EPHB2 Activates beta-Catenin to Enhance Cancer Stem Cell Properties and Drive Sorafenib Resistance in Hepatocellular Carcinoma.
Title: EPHB2 Activates β-Catenin to Enhance Cancer Stem Cell Properties and Drive Sorafenib Resistance in Hepatocellular Carcinoma.
Low Expression of EphB2, EphB3, and EphB4 in Bladder Cancer: Novel Potential Indicators of Muscular Invasion.
Title: Low Expression of EphB2, EphB3, and EphB4 in Bladder Cancer: Novel Potential Indicators of Muscular Invasion.
Loss of ephrin B2 receptor (EPHB2) sets lipid rheostat by regulating proteins DGAT1 and ATGL inducing lipid droplet storage in prostate cancer cells.
Title: Loss of ephrin B2 receptor (EPHB2) sets lipid rheostat by regulating proteins DGAT1 and ATGL inducing lipid droplet storage in prostate cancer cells.

Submit: New GeneRIF Correction See all GeneRIFs (94)

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	not available

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

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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

Gene Ontology Provided by GOA

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

Process	Evidence Code	Pubs
involved_in B cell activation	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in angiogenesis	ISS Inferred from Sequence or Structural Similarity more info
involved_in axon guidance	IBA Inferred from Biological aspect of Ancestor more info
involved_in axon guidance	ISS Inferred from Sequence or Structural Similarity more info
involved_in axonal fasciculation	ISS Inferred from Sequence or Structural Similarity more info
involved_in camera-type eye morphogenesis	IEA Inferred from Electronic Annotation more info
involved_in cellular response to amyloid-beta	IEA Inferred from Electronic Annotation more info
involved_in cellular response to lipopolysaccharide	IEA Inferred from Electronic Annotation more info
involved_in central nervous system projection neuron axonogenesis	IEA Inferred from Electronic Annotation more info
involved_in commissural neuron axon guidance	ISS Inferred from Sequence or Structural Similarity more info
involved_in corpus callosum development	ISS Inferred from Sequence or Structural Similarity more info
involved_in dendritic spine development	ISS Inferred from Sequence or Structural Similarity more info
involved_in dendritic spine morphogenesis	ISS Inferred from Sequence or Structural Similarity more info
involved_in ephrin receptor signaling pathway	IBA Inferred from Biological aspect of Ancestor more info
involved_in ephrin receptor signaling pathway	ISS Inferred from Sequence or Structural Similarity more info
involved_in hindbrain tangential cell migration	IEA Inferred from Electronic Annotation more info
involved_in inner ear morphogenesis	ISS Inferred from Sequence or Structural Similarity more info
involved_in learning	ISS Inferred from Sequence or Structural Similarity more info
involved_in learning or memory	ISS Inferred from Sequence or Structural Similarity more info
involved_in negative regulation of ERK1 and ERK2 cascade	ISS Inferred from Sequence or Structural Similarity more info
involved_in negative regulation of NMDA glutamate receptor activity	ISS Inferred from Sequence or Structural Similarity more info
involved_in negative regulation of Ras protein signal transduction	ISS Inferred from Sequence or Structural Similarity more info
involved_in negative regulation of axonogenesis	IEA Inferred from Electronic Annotation more info
involved_in negative regulation of cell adhesion	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in negative regulation of cytokine production involved in inflammatory response	IEA Inferred from Electronic Annotation more info
acts_upstream_of negative regulation of protein kinase activity	ISS Inferred from Sequence or Structural Similarity more info
involved_in negative regulation of protein phosphorylation	ISS Inferred from Sequence or Structural Similarity more info
involved_in nervous system development	TAS Traceable Author Statement more info	PubMed
involved_in neuron projection retraction	IEA Inferred from Electronic Annotation more info
involved_in optic nerve morphogenesis	IEA Inferred from Electronic Annotation more info
involved_in peptidyl-tyrosine phosphorylation	ISS Inferred from Sequence or Structural Similarity more info
involved_in phosphorylation	ISS Inferred from Sequence or Structural Similarity more info
involved_in positive regulation of B cell proliferation	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in positive regulation of NMDA glutamate receptor activity	ISS Inferred from Sequence or Structural Similarity more info
involved_in positive regulation of cell migration	IGI Inferred from Genetic Interaction more info	PubMed
involved_in positive regulation of dendritic spine morphogenesis	IEA Inferred from Electronic Annotation more info
involved_in positive regulation of gene expression	ISS Inferred from Sequence or Structural Similarity more info
involved_in positive regulation of immunoglobulin production	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in positive regulation of long-term neuronal synaptic plasticity	IEA Inferred from Electronic Annotation more info
involved_in positive regulation of long-term synaptic potentiation	ISS Inferred from Sequence or Structural Similarity more info
involved_in positive regulation of protein localization to cell surface	IEA Inferred from Electronic Annotation more info
involved_in positive regulation of protein localization to plasma membrane	ISS Inferred from Sequence or Structural Similarity more info
involved_in positive regulation of synapse assembly	ISS Inferred from Sequence or Structural Similarity more info
involved_in positive regulation of synaptic plasticity	ISS Inferred from Sequence or Structural Similarity more info
involved_in positive regulation of tumor necrosis factor production	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in postsynaptic membrane assembly	IEA Inferred from Electronic Annotation more info
involved_in regulation of T-helper 17 type immune response	IEA Inferred from Electronic Annotation more info
acts_upstream_of_positive_effect regulation of autophagosome assembly	IDA Inferred from Direct Assay more info	PubMed
involved_in regulation of behavioral fear response	IEA Inferred from Electronic Annotation more info
involved_in regulation of blood coagulation	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in regulation of body fluid levels	ISS Inferred from Sequence or Structural Similarity more info
involved_in regulation of filopodium assembly	IEA Inferred from Electronic Annotation more info
involved_in regulation of neuronal synaptic plasticity	ISS Inferred from Sequence or Structural Similarity more info
involved_in regulation of receptor signaling pathway via JAK-STAT	IEA Inferred from Electronic Annotation more info
involved_in retinal ganglion cell axon guidance	IEA Inferred from Electronic Annotation more info
involved_in roof of mouth development	ISS Inferred from Sequence or Structural Similarity more info
involved_in tight junction assembly	IEA Inferred from Electronic Annotation more info
involved_in urogenital system development	ISS Inferred from Sequence or Structural Similarity more info
involved_in vesicle-mediated intercellular transport	IEA Inferred from Electronic Annotation more info

Component	Evidence Code	Pubs
located_in axon	ISS Inferred from Sequence or Structural Similarity more info
located_in cell surface	IEA Inferred from Electronic Annotation more info
located_in cytosol	TAS Traceable Author Statement more info
is_active_in dendrite	IBA Inferred from Biological aspect of Ancestor more info
located_in dendrite	ISS Inferred from Sequence or Structural Similarity more info
located_in dendritic spine	IEA Inferred from Electronic Annotation more info
located_in extracellular region	TAS Traceable Author Statement more info
located_in glutamatergic synapse	IEA Inferred from Electronic Annotation more info
located_in hippocampal mossy fiber to CA3 synapse	IEA Inferred from Electronic Annotation more info
located_in neuronal cell body	IEA Inferred from Electronic Annotation more info
located_in nucleoplasm	IDA Inferred from Direct Assay more info
is_active_in plasma membrane	IBA Inferred from Biological aspect of Ancestor more info
located_in plasma membrane	IDA Inferred from Direct Assay more info
located_in plasma membrane	ISS Inferred from Sequence or Structural Similarity more info
located_in plasma membrane	TAS Traceable Author Statement more info
located_in postsynapse	TAS Traceable Author Statement more info	PubMed
located_in postsynaptic membrane	IEA Inferred from Electronic Annotation more info
located_in presynaptic membrane	IEA Inferred from Electronic Annotation more info

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_047305060.1

EC 2.7.10.1

XP_054191013.1

EC 2.7.10.1

XP_054191014.1

EC 2.7.10.1

XP_054191015.1

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

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

O43477, P29323, Q5T0U6, Q5T0U7, Q5T0U8

UniProtKB/TrEMBL

Q4LE53

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/TrEMBL

Q4LE53

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/TrEMBL

Q4LE53

Related

ENSP00000363761.3, ENST00000374630.8

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: GCF_000001405.40-RS_2024_08

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

Reference GRCh38.p14 Primary Assembly

Genomic

NC_000001.11 Reference GRCh38.p14 Primary Assembly

Range

22710838..22921500

Download

GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

XM_006710442.5 → XP_006710505.1 ephrin type-B receptor 2 isoform X2

UniProtKB/TrEMBL

Q4LE53

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_047449104.1 → XP_047305060.1 ephrin type-B receptor 2 isoform X3
XM_006710441.5 → XP_006710504.1 ephrin type-B receptor 2 isoform X1

UniProtKB/TrEMBL

Q4LE53

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