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Ephrin receptor

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[[Image:3hei.png|left|200px|thumb|Crystal Structure of ephrin A2 receptor complex with ephrin, [[3hei]]]]
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<StructureSection load='' size='350' side='right' scene='45/450911/Cv/1' caption='Human ephrin A3 receptor (magenta) complex with peptide substrate (green), nucleotide derivative and Mg+2 ion [[3fxx]]'>
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{{STRUCTURE_3fxx| PDB=3fxx | SIZE=300| SCENE= |right|CAPTION=Human ephrin A3 receptor (grey) complex with peptide substrate (green), nucleotide derivative (stick model) and Mg+2 ion [[3fxx]] }}
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'''Ephrin receptors''' (EPH) are components of the cell signaling pathways. They belong to the receptor tyrosine kinases. The extracellular ligand-binding domain (LBD) interacts with ephrin. EPH contains a sterile-α-motif (SAM) domain and a second fibronectin III domain (fn3). For more details see [[ Ephrin Type-A Receptor]].
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== Function ==
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== 3D Structures of ephrin receptors ==
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'''Ephrin receptors''' (EPHR) are components of the cell signaling pathways. They belong to the [[receptor tyrosine kinases]]. The extracellular ligand-binding domain (LBD) interacts with ephrin<ref>PMID:21078817</ref>.
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*'''Ephrin receptor A2''' functions in entry of Epstein-Barr virus to epithelial cells<ref>PMID:29292384</ref>.
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*'''Ephrin receptor A4''' functions in entry of Kaposi's sarcoma-associated herpesvirus to cells<ref>PMID:30782663</ref>.
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*'''Ephrin receptor A5''' is expressed in the nervous system and plays a role in synaptogenesis<ref>PMID:20824214</ref>.
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*'''Ephrin receptor A7''' functions in corticogenesis<ref>PMID:34176129</ref>.
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*'''Ephrin receptor A8''' has a role in short-range contact-mediated axonal guidance.
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*'''Ephrin receptor B4''' determine the molecular distinction between veins and arteries in the early embryo<ref>PMID:26817610</ref>.
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*'''Ephrin receptor B6''' functions in cold immune microenvironment and promotes the immune escape in BLCA<ref>PMID:37637034</ref>.
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For more details see [[Ephrin Type-A Receptor]] and [[Kinase-linked, enzyme-linked and related receptors]].
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Updated on {{REVISIONDAY2}}-{{MONTHNAME|{{REVISIONMONTH}}}}-{{REVISIONYEAR}}
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==Relevance ==
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===Ephrin A1 receptor===
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EPHR and ephrins can act as both tumor suppressors and tumor enhancers depending on the context<ref>PMID:20810264</ref>.
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[[3kka]] - hEPH A1 SAM+ hEPH A2 SAM – human<BR />
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[[3hil]] - hEPH A1 SAM<br />
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[[2k1l]] - hEPH A1 transmembrane domain – NMR<BR />
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[[1x5a]] - hEPH A1 fn3 domain – NMR<BR />
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===Ephrin A2 receptor===
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[[3hpn]], [[3c8x]] - hEPH A2 LBD<BR />
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[[2x10]], [[3fl7]] - hEPH A2 ectodomain<BR />
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[[2k9y]], [[2e8n]] - hEPH A2 transmembrane domain – NMR<BR />
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[[1mqb]] - hEPH A2 kinase domain<BR />
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''Ephrin A2 receptor binary complex''<br />
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== Structural highlights ==
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[[3mx0]], [[2x11]] - hEPH A2 ectodomain + ephrin A5<BR />
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EPHR domains include an ectodomain (residues 23-435) containing the LBD (residues 23-326), a second fibronectin III domain (fn3) (residues 446-539), a transmembrane domain (residues 539-563), a kinase domain (residues 596-900) and a sterile-α-motif (SAM) domain (residues 908-972).
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[[3hei]], [[3czu]] - hEPH A2 LBD + ephrin A1<BR />
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[[3mbw]] - hEPH A2 LBD + carbohydrate-recognition domain + ephrin A1<br />
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[[2kso]] - hEPH A2 SAM + SHIP2<br />
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===Ephrin A3 receptor===
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[[2qo2]], [[2qob]], [[2gsf]] - hEPH A3 kinase domain<BR />
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[[2qok]], [[2qol]], [[2qon]], [[2qoo]], [[2qod]], [[2qof]], [[2qoi]] - hEPH A3 kinase domain (mutant) <BR />
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[[3fxx]], [[3fy2]] – hEPH A3 kinase domain + peptide substrate<BR />
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[[2qoq]], [[2qo7]], [[2qo9]], [[2qoc]] - hEPH A3 kinase domain + AMP-PNP<BR />
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[[3dzq]] - hEPH A3 kinase domain + inhibitor<br />
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[[4g2f]] - hEPH A3 kinase domain (mutant) + inhibitor<br />
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===Ephrin A4 receptor===
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[[2wo1]], [[3ckh]] - hEPH A4 LBD<BR />
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[[4bk4]], [[4m4p]] - hEPH A4 ectodomain<br />
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[[2lw8]] - hEPH A4 LBD – NMR<br />
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[[2hel]] – mEPH A4 membrane and kinase domains – mouse<br />
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[[2y6m]] – mEPH A4 kinase domain<br />
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''Ephrin A4 receptor binary complex''<br />
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<scene name='45/450911/Cv/8'>Ephrin A3 receptor with peptide substrate, nucleotide derivative and Mg+2 ion</scene>. Water molecules are shown as red spheres.
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[[2wo3]] - hEPH A4 LBD + ephrin A2 receptor-binding domain<BR />
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<scene name='45/450911/Cv/9'>Nucleotide derivative and Mg+2 ion binding site</scene>.
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[[2wo2]], [[3gxu]] - hEPH A4 LBD + ephrin B2 receptor-binding domain<br />
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[[4bk5]], [[4bka]], [[4m4r]] - hEPH A4 ectodomain + ephrin A5 LBD<br />
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[[4bkf]] - hEPH A4 ectodomain + ephrin B3 LBD<br />
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[[2xyu]] – mEPH A4 kinase domain + inhibitor<br />
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[[2y6o]] – mEPH A4 kinase domain + cancer drug<br />
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===Ephrin A5 receptor===
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[[2r2p]] - hEPH A5 kinase domain<BR />
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[[1shx]] - mEPH A5 <br />
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[[4et7]] – hEPH A5 (mutant)<br />
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===Ephrin A7 receptor===
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[[3nru]] – hEPH A7 LBD<BR />
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[[3h8m]] – hEPH A7 SAM<BR />
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[[2rei]] - hEPH A7 kinase domain<BR />
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[[3dko]] – hEPH A7 kinase domain + inhibitor
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===Ephrin A8 receptor===
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[[3kul]] - hEPH A8 kinase domain<BR />
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[[1x5l]] – hEPH A8 fn3 domain – NMR<BR />
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[[1ucv]] - hEPH A8 SAM – NMR<BR />
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===Ephrin B1 receptor===
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[[2eao]] – hEPH B1 SAM – NMR<BR />
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[[2djs]] - hEPH B1 fn3 domain – NMR<BR />
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[[3zfx]] - hEPH B1 kinase domain<br />
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===Ephrin B2 receptor===
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[[3etp]] – hEPH B2<BR />
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[[1f0m]] – mEPH B2 SAM<BR />
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[[1iko]] - mEPH B2 ectodomain<br />
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[[2i85]] - hEPH B2 ectodomain<br />
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[[1sgg]] - mEPH B2 SAM – chicken - NMR<BR />
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''Ephrin B2 receptor binary complex''<br />
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<scene name='45/450911/Cv/10'>Peptide substrate binding site</scene> ([[3fxx]]).<ref>PMID:19678838</ref>
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[[2vsk]], [[2vsm]] – hEPH B2 + Viral Hemagglutinin-neuraminidase<BR />
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== 3D Structures of ephrin receptor ==
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[[2qbx]] – hEPH B2 + peptide agonist<BR />
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[[Ephrin receptor 3D structures]]
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[[2hen]] - hEPH B2 kinase domain + ADP<BR />
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[[1shw]] - mEPH B2 LBD + ephrin A5<BR />
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[[1kgy]] - mEPH B2 LBD + ephrin B2 extracellular domain<BR />
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===Ephrin B3 receptor===
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</StructureSection>
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[[3p1i]] – hEPH B3 LBD<BR />
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[[3zfy]] - hEPH B3 kinase domain<br />
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===Ephrin B4 receptor===
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[[2qkq]] – hEPH B4 SAM<BR />
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[[2e7h]] – hEPH B4 fn3 domain - NMR<BR />
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[[2x9f]], [[2vwy]] - hEPH B4 kinase domain (mutant) <BR />
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''Ephrin B4 receptor binary complex''<br />
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[[2vwx]], [[2vwz]], [[2vx0]], [[2vx1]], [[2vwu]], [[2vwv]], [[2vww]], [[4aw5]] – hEPH B4 kinase domain + inhibitor <BR />
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[[3zew]] - hEPH B4 + staurosporine<br />
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[[2xvd]], [[2yn8]], [[4bb4]] - hEPH B4 kinase domain (mutant) + inhibitor<br />
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[[2hle]], [[2bba]] - hEPH B4 LBD + ephrin B2
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== References ==
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<references/>
[[Category:Topic Page]]
[[Category:Topic Page]]

Current revision

Human ephrin A3 receptor (magenta) complex with peptide substrate (green), nucleotide derivative and Mg+2 ion 3fxx

Drag the structure with the mouse to rotate

References

  1. ↑ Pitulescu ME, Adams RH. Eph/ephrin molecules--a hub for signaling and endocytosis. Genes Dev. 2010 Nov 15;24(22):2480-92. doi: 10.1101/gad.1973910. PMID:21078817 doi:http://dx.doi.org/10.1101/gad.1973910
  2. ↑ Chen J, Sathiyamoorthy K, Zhang X, Schaller S, Perez White BE, Jardetzky TS, Longnecker R. Ephrin receptor A2 is a functional entry receptor for Epstein-Barr virus. Nat Microbiol. 2018 Feb;3(2):172-180. PMID:29292384 doi:10.1038/s41564-017-0081-7
  3. ↑ Chen J, Zhang X, Schaller S, Jardetzky TS, Longnecker R. Ephrin Receptor A4 is a New Kaposi's Sarcoma-Associated Herpesvirus Virus Entry Receptor. mBio. 2019 Feb 19;10(1):e02892-18. PMID:30782663 doi:10.1128/mBio.02892-18
  4. ↑ Akaneya Y, Sohya K, Kitamura A, Kimura F, Washburn C, Zhou R, Ninan I, Tsumoto T, Ziff EB. Ephrin-A5 and EphA5 interaction induces synaptogenesis during early hippocampal development. PLoS One. 2010 Aug 31;5(8):e12486. PMID:20824214 doi:10.1371/journal.pone.0012486
  5. ↑ Lévy J, Schell B, Nasser H, Rachid M, Ruaud L, Couque N, Callier P, Faivre L, Marle N, Engwerda A, van Ravenswaaij-Arts CMA, Plutino M, Karmous-Benailly H, Benech C, Redon S, Boute O, Boudry Labis E, Rama M, Kuentz P, Assoumani J, Maldergem LV, Dupont C, Verloes A, Tabet AC. EPHA7 haploinsufficiency is associated with a neurodevelopmental disorder. Clin Genet. 2021 Oct;100(4):396-404. PMID:34176129 doi:10.1111/cge.14017
  6. ↑ Wang M, Collins MJ, Foster TR, Bai H, Hashimoto T, Santana JM, Shu C, Dardik A. Eph-B4 mediates vein graft adaptation by regulation of endothelial nitric oxide synthase. J Vasc Surg. 2017 Jan;65(1):179-189. PMID:26817610 doi:10.1016/j.jvs.2015.11.041
  7. ↑ Jia X, Zhang D, Zhou C, Yan Z, Jiang Z, Xie L, Jiang J. Eph receptor B6 shapes a cold immune microenvironment, inhibiting anti-cancer immunity and immunotherapy response in bladder cancer. Front Oncol. 2023 Aug 9;13:1175183. PMID:37637034 doi:10.3389/fonc.2023.1175183
  8. ↑ Genander M, Frisen J. Ephrins and Eph receptors in stem cells and cancer. Curr Opin Cell Biol. 2010 Oct;22(5):611-6. doi: 10.1016/j.ceb.2010.08.005. PMID:20810264 doi:http://dx.doi.org/10.1016/j.ceb.2010.08.005
  9. ↑ Davis TL, Walker JR, Allali-Hassani A, Parker SA, Turk BE, Dhe-Paganon S. Structural recognition of an optimized substrate for the ephrin family of receptor tyrosine kinases. FEBS J. 2009 Aug;276(16):4395-404. PMID:19678838 doi:http://dx.doi.org/10.1111/j.1742-4658.2009.07147.x

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