Target Information
| Target General Information | Top | |||||
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| Target ID |
T02446
(Former ID: TTDI03180)
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| Target Name |
Ephrin type-B receptor 1 (EPHB1)
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| Synonyms |
hEK6; Tyrosine-protein kinase receptor EPH-2; Neuronally-expressed EPH-related tyrosine kinase; EPHT2; EPH-like kinase 6; EPH tyrosine kinase 2; ELK; EK6
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| Gene Name |
EPHB1
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| Target Type |
Literature-reported target
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[1] | ||||
| Function |
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. Cognate/functional ephrin ligands for this receptor include EFNB1, EFNB2 and EFNB3. During nervous system development, regulates retinal axon guidance redirecting ipsilaterally ventrotemporal retinal ganglion cells axons at the optic chiasm midline. This probably requires repulsive interaction with EFNB2. In the adult nervous system together with EFNB3, regulates chemotaxis, proliferation and polarity of the hippocampus neural progenitors. In addition to its role in axon guidance plays also an important redundant role with other ephrin-B receptors in development and maturation of dendritic spines and synapse formation. May also regulate angiogenesis. More generally, may play a role in targeted cell migration and adhesion. Upon activation by EFNB1 and probably other ephrin-B ligands activates the MAPK/ERK and the JNK signaling cascades to regulate cell migration and adhesion respectively. Involved in the maintenance of the pool of satellite cells (muscle stem cells) by promoting their self-renewal and reducing their activation and differentiation. Receptor tyrosine kinase which binds promiscuously transmembrane ephrin-B family ligands residing on adjacent cells, leading to contact-dependent bidirectional signaling into neighboring cells.
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| BioChemical Class |
Kinase
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| UniProt ID | ||||||
| EC Number |
EC 2.7.10.1
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| Sequence |
MALDYLLLLLLASAVAAMEETLMDTRTATAELGWTANPASGWEEVSGYDENLNTIRTYQV
CNVFEPNQNNWLLTTFINRRGAHRIYTEMRFTVRDCSSLPNVPGSCKETFNLYYYETDSV IATKKSAFWSEAPYLKVDTIAADESFSQVDFGGRLMKVNTEVRSFGPLTRNGFYLAFQDY GACMSLLSVRVFFKKCPSIVQNFAVFPETMTGAESTSLVIARGTCIPNAEEVDVPIKLYC NGDGEWMVPIGRCTCKPGYEPENSVACKACPAGTFKASQEAEGCSHCPSNSRSPAEASPI CTCRTGYYRADFDPPEVACTSVPSGPRNVISIVNETSIILEWHPPRETGGRDDVTYNIIC KKCRADRRSCSRCDDNVEFVPRQLGLTECRVSISSLWAHTPYTFDIQAINGVSSKSPFPP QHVSVNITTNQAAPSTVPIMHQVSATMRSITLSWPQPEQPNGIILDYEIRYYEKEHNEFN SSMARSQTNTARIDGLRPGMVYVVQVRARTVAGYGKFSGKMCFQTLTDDDYKSELREQLP LIAGSAAAGVVFVVSLVAISIVCSRKRAYSKEAVYSDKLQHYSTGRGSPGMKIYIDPFTY EDPNEAVREFAKEIDVSFVKIEEVIGAGEFGEVYKGRLKLPGKREIYVAIKTLKAGYSEK QRRDFLSEASIMGQFDHPNIIRLEGVVTKSRPVMIITEFMENGALDSFLRQNDGQFTVIQ LVGMLRGIAAGMKYLAEMNYVHRDLAARNILVNSNLVCKVSDFGLSRYLQDDTSDPTYTS SLGGKIPVRWTAPEAIAYRKFTSASDVWSYGIVMWEVMSFGERPYWDMSNQDVINAIEQD YRLPPPMDCPAALHQLMLDCWQKDRNSRPRFAEIVNTLDKMIRNPASLKTVATITAVPSQ PLLDRSIPDFTAFTTVDDWLSAIKMVQYRDSFLTAGFTSLQLVTQMTSEDLLRIGITLAG HQKKILNSIHSMRVQISQSPTAMA Click to Show/Hide
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| 3D Structure | Click to Show 3D Structure of This Target | AlphaFold | ||||
| HIT2.0 ID | T80LLJ | |||||
| Cell-based Target Expression Variations | Top | |||||
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| Cell-based Target Expression Variations | ||||||
| Drug Binding Sites of Target | Top | |||||
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| Ligand Name: Chlortetracycline | Ligand Info | |||||
| Structure Description | Crystal structure of hEphB1 bound with chlortetracycline | PDB:6UMW | ||||
| Method | X-ray diffraction | Resolution | 1.98 Å | Mutation | No | [3] |
| PDB Sequence |
AKEIDVSFVK
620 IEEVIGAGEF630 GEVYKGRLKL640 PGKREIVAIK651 TLKAGYSEKQ661 RRDFLSEASI 671 MGQFDHPNII681 RLEGVVTKSR691 PVMIITEFME701 NGALDSFLRQ711 NDGQFTVIQL 721 VGMLRGIAAG731 MKYLAEMNYV741 HRDLAARNIL751 VNSNLVCKVS761 DFIPVRWTAP 793 EAIAYRKFTS803 ASDVWSYGIV813 MWEVMSFGER823 PYWDMSNQDV833 INAIEQDYRL 843 PPPMDCPAAL853 HQLMLDCWQK863 DRNSRPRFAE873 IVNTLDKMIR883 NPASLK |
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ILE625
3.776
GLY626
4.828
VAL633
3.742
ALA649
3.344
ILE650
4.748
LYS651
2.860
GLU668
4.430
MET672
2.884
ILE681
3.091
ILE695
4.275
THR697
2.362
GLU698
3.047
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| Ligand Name: adenosine diphosphate | Ligand Info | |||||
| Structure Description | Crystal structure of hEphB1 bound with ADP | PDB:7KPM | ||||
| Method | X-ray diffraction | Resolution | 1.61 Å | Mutation | No | [3] |
| PDB Sequence |
AKEIDVSFVK
620 IEEVIGAGEF630 GEVYKGRLKL640 PGKREIVAIK651 TLKAGYSEKQ661 RRDFLSEASI 671 MGQFDHPNII681 RLEGVVTKSR691 PVMIITEFME701 NGALDSFLRQ711 NDGQFTVIQL 721 VGMLRGIAAG731 MKYLAEMNYV741 HRDLAARNIL751 VNSNLVCKVS761 DFPVRWTAPE 794 AIAYRKFTSA804 SDVWSYGIVM814 WEVMSFGERP824 YWDMSNQDVI834 NAIEQDYRLP 844 PPMDCPAALH854 QLMLDCWQKD864 RNSRPRFAEI874 VNTLDKMIRN884 PASL |
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ILE625
3.606
GLY626
3.507
ALA627
3.520
GLY628
3.108
GLU629
3.145
PHE630
2.700
GLY631
3.444
VAL633
3.617
ALA649
3.419
LYS651
2.638
THR652
4.749
PHE665
4.261
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| Click to View More Binding Site Information of This Target with Different Ligands | ||||||
| Different Human System Profiles of Target | Top |
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Human Similarity Proteins
of target is determined by comparing the sequence similarity of all human proteins with the target based on BLAST. The similarity proteins for a target are defined as the proteins with E-value < 0.005 and outside the protein families of the target.
A target that has fewer human similarity proteins outside its family is commonly regarded to possess a greater capacity to avoid undesired interactions and thus increase the possibility of finding successful drugs
(Brief Bioinform, 21: 649-662, 2020).
Human Tissue Distribution
of target is determined from a proteomics study that quantified more than 12,000 genes across 32 normal human tissues. Tissue Specificity (TS) score was used to define the enrichment of target across tissues.
The distribution of targets among different tissues or organs need to be taken into consideration when assessing the target druggability, as it is generally accepted that the wider the target distribution, the greater the concern over potential adverse effects
(Nat Rev Drug Discov, 20: 64-81, 2021).
Human Pathway Affiliation
of target is determined by the life-essential pathways provided on KEGG database. The target-affiliated pathways were defined based on the following two criteria (a) the pathways of the studied target should be life-essential for both healthy individuals and patients, and (b) the studied target should occupy an upstream position in the pathways and therefore had the ability to regulate biological function.
Targets involved in a fewer pathways have greater likelihood to be successfully developed, while those associated with more human pathways increase the chance of undesirable interferences with other human processes
(Pharmacol Rev, 58: 259-279, 2006).
Biological Network Descriptors
of target is determined based on a human protein-protein interactions (PPI) network consisting of 9,309 proteins and 52,713 PPIs, which were with a high confidence score of ≥ 0.95 collected from STRING database.
The network properties of targets based on protein-protein interactions (PPIs) have been widely adopted for the assessment of target’s druggability. Proteins with high node degree tend to have a high impact on network function through multiple interactions, while proteins with high betweenness centrality are regarded to be central for communication in interaction networks and regulate the flow of signaling information
(Front Pharmacol, 9, 1245, 2018;
Curr Opin Struct Biol. 44:134-142, 2017).
Human Similarity Proteins
Human Tissue Distribution
Human Pathway Affiliation
Biological Network Descriptors
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Note:
If a protein has TS (tissue specficity) scores at least in one tissue >= 2.5, this protein is called tissue-enriched (including tissue-enriched-but-not-specific and tissue-specific). In the plots, the vertical lines are at thresholds 2.5 and 4.
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| KEGG Pathway | Pathway ID | Affiliated Target | Pathway Map |
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| Axon guidance | hsa04360 | Affiliated Target |
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| Class: Organismal Systems => Development and regeneration | Pathway Hierarchy | ||
| Degree | 10 | Degree centrality | 1.07E-03 | Betweenness centrality | 1.05E-04 |
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| Closeness centrality | 2.18E-01 | Radiality | 1.38E+01 | Clustering coefficient | 4.44E-02 |
| Neighborhood connectivity | 3.46E+01 | Topological coefficient | 1.61E-01 | Eccentricity | 12 |
| Download | Click to Download the Full PPI Network of This Target | ||||
| Chemical Structure based Activity Landscape of Target | Top |
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| Target Regulators | Top | |||||
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| Target-interacting Proteins | ||||||
| References | Top | |||||
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| REF 1 | Structure-based optimization of potent and selective inhibitors of the tyrosine kinase erythropoietin producing human hepatocellular carcinoma receptor B4 (EphB4). J Med Chem. 2009 Oct 22;52(20):6433-46. | |||||
| REF 2 | Amino acid conjugates of lithocholic acid as antagonists of the EphA2 receptor. J Med Chem. 2013 Apr 11;56(7):2936-47. | |||||
| REF 3 | Identification of tetracycline combinations as EphB1 tyrosine kinase inhibitors for treatment of neuropathic pain. Proc Natl Acad Sci U S A. 2021 Mar 9;118(10):e2016265118. | |||||
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