Tchem EPHB4 Ephrin type-B receptor 4

Protein Classes

DTO Classes

Protein / Kinase / Protein Kinase / Tk Group / Eph Family / Ephrin Type-b Receptor 4

Protein Summary

Description

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. Together with its cognate ligand/functional ligand EFNB2 plays a central role in heart morphogenesis and angiogenesis through regulation of cell adhesion and cell migration. EPHB4-mediated forward signaling controls cellular repulsion and segregation form EFNB2-expressing cells. Plays also a role in postnatal blood vessel remodeling, morphogenesis and permeability and is thus important in the context of tumor angiogenesis. Ephrin receptors and their ligands, the ephrins, mediate numerous developmental processes, particularly in the nervous system. Based on their structures and sequence relationships, ephrins are divided into the ephrin-A (EFNA) class, which are anchored to the membrane by a glycosylphosphatidylinositol linkage, and the ephrin-B (EFNB) class, which are transmembrane proteins. The Eph family of receptors are divided into 2 groups based on the similarity of their extracellular domain sequences and their affinities for binding ephrin-A and ephrin-B ligands. Ephrin receptors make up the largest subgroup of the receptor tyrosine kinase (RTK) family. The protein encoded by this gene binds to ephrin-B2 and plays an essential role in vascular development. [provided by RefSeq, Jul 2008]

Uniprot Accession IDs

• P54760
• B5A970
• B5A971
• B5A972
• Q7Z635
• Q9BTA5
• Q9BXP0

Gene Name

• EPHB4

Ensembl ID

• ENST00000358173
• ENSP00000350896
• ENSG00000196411
• ENST00000616502
• ENSP00000482702

Symbol

• HTK
• MYK1
• TYRO11
• HTK
• MYK1
• HFASD
• CMAVM2
• LMPHM7
• TYRO11

Knowledge Table

Most Knowledge About	Knowledge Value (0 to 1 scale)
protein domain	1
molecular function	0.98
PubMedID	0.86
transcription factor binding site profile	0.83
kinase perturbation	0.81

Related Tools

ProKinO

The ProKinO is a protein kinase-specific ontology, which provides a controlled vocabulary of terms, their hierarchy, and relationships unifying sequence, structure, function, mutation and pathway information on kinases.

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Target Illumination GWAS Analytics (TIGA)

TIGA scores and ranks GWAS discovered associations according to the quantity and quality of the evidence supporting the association.

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GENEVA

GENEVA (GENe Expression Variance Analysis) allows you to identify RNA-sequencing datasets from the Gene Expression Omnibus (GEO) that contain conditions modulating a gene or a gene signature.

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GlyGen

GlyGen is a data integration and dissemination project for carbohydrate and glycoconjugate related data.

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IDG Development Level Summary

Tdark

These are targets about which virtually nothing is known. They do not have known drug or small molecule activities
- AND - satisfy two or more of the following criteria:

Pubmed score: 294.21   (req: < 5)

Gene RIFs: 100   (req: <= 3)

Antibodies: 627   (req: <= 50)

Tbio

These targets do not have known drug or small molecule activities
- AND - satisfy two or more of the following criteria:

Pubmed score: 294.21   (req: >= 5)

Gene RIFs: 100   (req: > 3)

Antibodies: 627   (req: > 50)

- OR - satisfy the following criterion:

Gene Ontology Terms: 16

Tchem

Target has at least one ChEMBL compound with an activity cutoff of < 30 nM - AND - satisfies the preceding conditions

Active Ligands: 106

Tclin

Target has at least one approved drug - AND - satisfies the preceding conditions

Active Drugs: 3

Approved Drugs (3)

Explore Approved Drugs

1 – 3 of 3

bosutinib

EPHB4Tchem Kinase

Kd : 8.04

dasatinib

EPHB4Tchem Kinase

Kd : 9.47

sorafenib

EPHB4Tchem Kinase

IC50 : 9.7

Active Ligands (106)

Explore Active Ligands

1 – 10 of 106

foretinib

EPHB4Tchem Kinase

Kd : 7.92

PD-173955

EPHB4Tchem Kinase

Kd : 7.92

TG-100572

EPHB4Tchem Kinase

Kd : 9.05

danusertib

EPHB4Tchem Kinase

Kd : 7.75

CHEMBL566515

EPHB4Tchem Kinase

IC50 : 8.80000019

CHEMBL459850

EPHB4Tchem Kinase

EC50 : 8.4

compound 20 [PMID: 23489211]

EPHB4Tchem Kinase

IC50 : 5.36000013

CHEMBL1241676

EPHB4Tchem Kinase

IC50 : 7.75

CHEMBL256101

EPHB4Tchem Kinase

Ki : 8.14

tesevatinib

EPHB4Tchem Kinase

IC50 : 8.85000038

GWAS Traits (28)

• Explore on Target Illumination GWAS Analytics (TIGA)

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5

1 – 5 of 28

GWAS Trait	EFO ID	Study Count	SNP Count	Beta Count	Odds Ratio	Evidence (Mean Rank Score)	Provenance
hematocrit	EFO_0004348	4	6	9		99.1
hemoglobin measurement	EFO_0004509	4	4	7		98
sex hormone-binding globulin measurement	EFO_0004696	6	3	6		96.5
erythrocyte count	EFO_0004305	2	3	3		95.8
hair color	EFO_0003924	1	3	0	1.1	93.5

• Explore on Target Illumination GWAS Analytics (TIGA)

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1 – 5 of 28

GWAS Trait	EFO ID	Beta Count	Odds Ratio	Evidence (Mean Rank Score)	Provenance
hematocrit	EFO_0004348	9		99.1
hemoglobin measurement	EFO_0004509	7		98
sex hormone-binding globulin measurement	EFO_0004696	6		96.5
erythrocyte count	EFO_0004305	3		95.8
hair color	EFO_0003924	0	1.1	93.5

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Orthologs (11)

1 – 5 of 11

Species	Name	Source ID	Gene ID	OMA	EggNOG	Inparanoid
Chimp	EPH receptor B4	VGNC:4339	463610
Macaque	EPH receptor B4		719320
Mouse	Eph receptor B4	MGI:104757	13846
Rat	EPH receptor B4	RGD:1583193	686310
Dog	EPH receptor B4	VGNC:40413	489830

Species	Name	OMA	EggNOG	Inparanoid
Chimp	EPH receptor B4
Macaque	EPH receptor B4
Mouse	Eph receptor B4
Rat	EPH receptor B4
Dog	EPH receptor B4

Protein Structure (23 Structures, 1 AlphaFold Model)

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Representation

  axes   backbone   ball+stick   cartoon   rocket   rope   spacefill

Color Scheme

  target   atomindex   bfactor   chainname   electrostatic   element   hydrophobicity   resname   sstruc

Click on a row in the table to change the structure displayed.
More information can be found at RCSB PDB

AF-P54760-F1-model_v1

AlphaFold Structures Developed by DeepMind and EMBL-EBI

1 – 5 of 23

PDB Structure Id	Ligand	Method	Resolution (Å)	Residues	Fraction of Total Protein	Pub Year	Title

PDB Structure Id	Fraction of Total Protein	Resolution	Pub Year

Pathways (25)

Reactome (5)

KEGG (1)

PathwayCommons (4)

WikiPathways (15)

Axon guidance (R-HSA-422475)

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Find Similar Targets

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5

1 – 5 of 5

Data Source	Name	Explore in Pharos	Explore in Source
Reactome	Axon guidance	533 targets	R-HSA-422475
Reactome	Developmental Biology	1055 targets	R-HSA-1266738
Reactome	EPH-Ephrin signaling	92 targets	R-HSA-2682334
Reactome	EPH-ephrin mediated repulsion of cells	49 targets	R-HSA-3928665
Reactome	Ephrin signaling	19 targets	R-HSA-3928664

Name	Explore in Pharos	Explore in Source
Axon guidance	533 targets	R-HSA-422475
Developmental Biology	1055 targets	R-HSA-1266738
EPH-Ephrin signaling	92 targets	R-HSA-2682334
EPH-ephrin mediated repulsion of cells	49 targets	R-HSA-3928665
Ephrin signaling	19 targets	R-HSA-3928664

Gene Ontology Terms (24)

Functions (6)

Components (8)

Processes (10)

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10

1 – 6 of 6

GO Term	Evidence	Assigned by
protein tyrosine kinase activity	Inferred from Experiment (EXP)	Reactome
ephrin receptor activity	Inferred from Direct Assay (IDA)	UniProtKB
transmembrane receptor protein tyrosine kinase activity	Inferred from Direct Assay (IDA)	UniProtKB
transmembrane signaling receptor activity	Inferred from Biological aspect of Ancestor (IBA)	GO_Central
transmembrane-ephrin receptor activity	Inferred from Biological aspect of Ancestor (IBA)	GO_Central
ATP binding	Inferred from Electronic Annotation (IEA)	UniProtKB-KW

Protein-Protein Interactions (175)

Explore Interacting Targets

1 – 10 of 175

• See Interactions on String-DB

EFNB2

Tbio

Novelty:  0.00255095

p_int:  0.999998976

p_ni:  0.00000102

p_wrong:  4e-9

Score:  0.999

Data Source:  BioPlex,STRINGDB

SCGB2A2

Tbio

Novelty:  0.01594053

p_int:  0.997616025

p_ni:  0.002383948

p_wrong:  2.7e-8

Score:  0.198

Data Source:  BioPlex,STRINGDB

TCTN2

Tbio

Novelty:  0.11617528

p_int:  0.996846043

p_ni:  0.003153951

p_wrong:  7e-9

Data Source:  BioPlex

SCGB2A1

Tbio

Novelty:  0.01902973

p_int:  0.996237235

p_ni:  0.003762763

p_wrong:  2e-9

Data Source:  BioPlex

MANSC1

Tdark

Novelty:  0.91681036

p_int:  0.996172052

p_ni:  0.003827448

p_wrong:  5.01e-7

Data Source:  BioPlex

KLRG2

Tdark

Novelty:  1.19446694

p_int:  0.989727321

p_ni:  0.010271095

p_wrong:  0.000001584

Score:  0.172

Data Source:  BioPlex,STRINGDB

PCDHGA5

Tdark

Novelty:  2.13631603

p_int:  0.986744476

p_ni:  0.013236317

p_wrong:  0.000019207

Score:  0.172

Data Source:  BioPlex,STRINGDB

TMPRSS3

Tbio

Family:  Enzyme

Novelty:  0.0268524

p_int:  0.978692288

p_ni:  0.021119659

p_wrong:  0.000188053

Data Source:  BioPlex

GABRE

Tclin

Family:  IC

Novelty:  0.03814541

p_int:  0.977830344

p_ni:  0.022169655

p_wrong:  1e-9

Data Source:  BioPlex

HLA-DRA

Tbio

Novelty:  0.0060214

p_int:  0.977205536

p_ni:  0.022792663

p_wrong:  0.000001801

Data Source:  BioPlex

Publication Statistics

PubMed Score  294.21

PubMed score by year

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PubTator Score  166.17

PubTator score by year

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Patents

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Amino Acid Sequence

Residue Counts

Protein Sequence

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Ortholog Sequence Conservation

WebLogo Color Code

PolarG S T Y C

NeutralQ N

BasicK R H

AcidicD E

HydrophobicA V L I P W F M

Compare across kinases on ProKinO

Structural Annotations

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UniProt Keyword Find Similar Targets

No Header	No Header
3D-structure
Alternative splicing
Angiogenesis
ATP-binding
Cell membrane
Complete proteome
Developmental protein
Disulfide bond
Glycoprotein
Kinase

GWAS Trait Find Similar Targets

No Header	No Header
alkaline phosphatase measurement
BMI-adjusted waist circumference
body mass index
Crohn's disease
electrocardiography
erythrocyte count
hair color
heart rate
heart rate response to exercise
heart rate response to recovery post exercise

MGI Phenotype Find Similar Targets

No Header	No Header
cardiovascular system phenotype
embryo phenotype
growth/size/body region phenotype
mortality/aging
muscle phenotype
renal/urinary system phenotype