Tchem EPHB4 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

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: 340.26   (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: 340.26   (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: 73

Tclin

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

Active Drugs: 2

Approved Drugs (2)

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1 – 2 of 2

dasatinib

EPHB4Tchem Kinase

Kd: 9.47

bosutinib

EPHB4Tchem Kinase

Kd: 8.04

Active Ligands (73)

Explore Active Ligands

1 – 10 of 73

CHEMBL1230609

EPHB4Tchem Kinase

Kd: 7.92

CHEMBL386051

EPHB4Tchem Kinase

Kd: 7.92

CHEMBL566515

EPHB4Tchem Kinase

IC50: 8.80000019

CHEMBL400402

EPHB4Tchem Kinase

IC50: 7.8

compound 20 [PMID: 23489211]

EPHB4Tchem Kinase

IC50: 5.36000013

CHEMBL459850

EPHB4Tchem Kinase

EC50: 8.4

CHEMBL3787112

EPHB4Tchem Kinase

IC50: 8.3

CHEMBL1241676

EPHB4Tchem Kinase

IC50: 7.75

CHEMBL256101

EPHB4Tchem Kinase

Ki: 8.14

tesevatinib

EPHB4Tchem Kinase

IC50: 8.85000038

Protein Data Bank (23)

1 – 5 of 23

PDB Structure Id	Ligand	Method	Resolution (Å)	M.W. (kDa)	Pub Year	Title

PDB Structure Id	M.W.	Resolution	Pub Year

Pathways (25)

Reactome (5)

KEGG (1)

PathwayCommons (4)

WikiPathways (15)

Axon guidance (R-HSA-422475)

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Items per page:

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)

Items per page:

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)

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1 – 10 of 175

• See Interactions on String-DB

EFNB2

Tbio

Novelty: 0.00309066

p_int: 0.999998976

p_ni: 0.00000102

p_wrong: 4e-9

Score: 0.999

Data Source: BioPlex,STRINGDB

SCGB2A2

Tbio

Novelty: 0.01762536

p_int: 0.997616025

p_ni: 0.002383948

p_wrong: 2.7e-8

Score: 0.198

Data Source: BioPlex,STRINGDB

TCTN2

Tdark

Novelty: 0.19568118

p_int: 0.996846043

p_ni: 0.003153951

p_wrong: 7e-9

Data Source: BioPlex

SCGB2A1

Tbio

Novelty: 0.00455624

p_int: 0.996237235

p_ni: 0.003762763

p_wrong: 2e-9

Data Source: BioPlex

MANSC1

Tdark

Novelty: 1.42372881

p_int: 0.996172052

p_ni: 0.003827448

p_wrong: 5.01e-7

Data Source: BioPlex

KLRG2

Tdark

Novelty: 0.77419355

p_int: 0.989727321

p_ni: 0.010271095

p_wrong: 0.000001584

Score: 0.172

Data Source: BioPlex,STRINGDB

PCDHGA5

Tdark

p_int: 0.986744476

p_ni: 0.013236317

p_wrong: 0.000019207

Score: 0.172

Data Source: BioPlex,STRINGDB

TMPRSS3

Tbio

Family: Enzyme

Novelty: 0.03356847

p_int: 0.978692288

p_ni: 0.021119659

p_wrong: 0.000188053

Data Source: BioPlex

GABRE

Tclin

Family: IC

Novelty: 0.09719489

p_int: 0.977830344

p_ni: 0.022169655

p_wrong: 1e-9

Data Source: BioPlex

HLA-DRA

Tbio

Novelty: 0.00705028

p_int: 0.977205536

p_ni: 0.022792663

p_wrong: 0.000001801

Data Source: BioPlex

Publication Statistics

PubMed Score  340.26

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

Sequence

MELRVLLCWASLAAALEETLLNTKLETADLKWVTFPQVDGQWEELSGLDEEQHSVRTYEVCDVQRAPGQA

1-70

HWLRTGWVPRRGAVHVYATLRFTMLECLSLPRAGRSCKETFTVFYYESDADTATALTPAWMENPYIKVDT

70-140

VAAEHLTRKRPGAEATGKVNVKTLRLGPLSKAGFYLAFQDQGACMALLSLHLFYKKCAQLTVNLTRFPET

140-210

VPRELVVPVAGSCVVDAVPAPGPSPSLYCREDGQWAEQPVTGCSCAPGFEAAEGNTKCRACAQGTFKPLS

210-280

GEGSCQPCPANSHSNTIGSAVCQCRVGYFRARTDPRGAPCTTPPSAPRSVVSRLNGSSLHLEWSAPLESG

280-350

GREDLTYALRCRECRPGGSCAPCGGDLTFDPGPRDLVEPWVVVRGLRPDFTYTFEVTALNGVSSLATGPV

350-420

PFEPVNVTTDREVPPAVSDIRVTRSSPSSLSLAWAVPRAPSGAVLDYEVKYHEKGAEGPSSVRFLKTSEN

420-490

RAELRGLKRGASYLVQVRARSEAGYGPFGQEHHSQTQLDESEGWREQLALIAGTAVVGVVLVLVVIVVAV

490-560

LCLRKQSNGREAEYSDKHGQYLIGHGTKVYIDPFTYEDPNEAVREFAKEIDVSYVKIEEVIGAGEFGEVC

560-630

RGRLKAPGKKESCVAIKTLKGGYTERQRREFLSEASIMGQFEHPNIIRLEGVVTNSMPVMILTEFMENGA

630-700

LDSFLRLNDGQFTVIQLVGMLRGIASGMRYLAEMSYVHRDLAARNILVNSNLVCKVSDFGLSRFLEENSS

700-770

DPTYTSSLGGKIPIRWTAPEAIAFRKFTSASDAWSYGIVMWEVMSFGERPYWDMSNQDVINAIEQDYRLP

770-840

PPPDCPTSLHQLMLDCWQKDRNARPRFPQVVSALDKMIRNPASLKIVARENGGASHPLLDQRQPHYSAFG

840-910

SVGEWLRAIKMGRYEESFAAAGFGSFELVSQISAEDLLRIGVTLAGHQKKILASVQHMKSQAKPGTPGGT

910-980

GGPAPQY

980-987

MELRVLLCWASLAAALEETLLNTKLETADLKWVTFPQVDGQWEELSGLDEEQHSVRTYEVCDVQRAPGQAHWLRTGWVPRRGAVHVYATLRFTMLECLSLPRAGRSCKETFTVFYYESDADTATALTPAWMENPYIKVDTVAAEHLTRKRPGAEATGKVNVKTLRLGPLSKAGFYLAFQDQGACMALLSLHLFYKKCAQLTVNLTRFPETVPRELVVPVAGSCVVDAVPAPGPSPSLYCREDGQWAEQPVTGCSCAPGFEAAEGNTKCRACAQGTFKPLSGEGSCQPCPANSHSNTIGSAVCQCRVGYFRARTDPRGAPCTTPPSAPRSVVSRLNGSSLHLEWSAPLESGGREDLTYALRCRECRPGGSCAPCGGDLTFDPGPRDLVEPWVVVRGLRPDFTYTFEVTALNGVSSLATGPVPFEPVNVTTDREVPPAVSDIRVTRSSPSSLSLAWAVPRAPSGAVLDYEVKYHEKGAEGPSSVRFLKTSENRAELRGLKRGASYLVQVRARSEAGYGPFGQEHHSQTQLDESEGWREQLALIAGTAVVGVVLVLVVIVVAVLCLRKQSNGREAEYSDKHGQYLIGHGTKVYIDPFTYEDPNEAVREFAKEIDVSYVKIEEVIGAGEFGEVCRGRLKAPGKKESCVAIKTLKGGYTERQRREFLSEASIMGQFEHPNIIRLEGVVTNSMPVMILTEFMENGALDSFLRLNDGQFTVIQLVGMLRGIASGMRYLAEMSYVHRDLAARNILVNSNLVCKVSDFGLSRFLEENSSDPTYTSSLGGKIPIRWTAPEAIAFRKFTSASDAWSYGIVMWEVMSFGERPYWDMSNQDVINAIEQDYRLPPPPDCPTSLHQLMLDCWQKDRNARPRFPQVVSALDKMIRNPASLKIVARENGGASHPLLDQRQPHYSAFGSVGEWLRAIKMGRYEESFAAAGFGSFELVSQISAEDLLRIGVTLAGHQKKILASVQHMKSQAKPGTPGGTGGPAPQY

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Uniprot Keyword

3D-structure
Alternative splicing
Angiogenesis
ATP-binding
Cell membrane
Complete proteome
Developmental protein
Disulfide bond
Glycoprotein
Kinase