Ephrin receptor

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Contents

Function

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[1].

  • Ephrin receptor A2 functions in entry of Epstein-Barr virus to epithelial cells[2].
  • Ephrin receptor A4 functions in entry of Kaposi's sarcoma-associated herpesvirus to cells[3].
  • Ephrin receptor A5 is expressed in the nervous system and plays a role in synaptogenesis[4].
  • Ephrin receptor A7 functions in corticogenesis[5].
  • Ephrin receptor A8 has a role in short-range contact-mediated axonal guidance.
  • Ephrin receptor B4 determine the molecular distinction between veins and arteries in the early embryo[6].
  • Ephrin receptor B6 functions in cold immune microenvironment and promotes the immune escape in BLCA[7].

For more details see Ephrin Type-A Receptor and Kinase-linked, enzyme-linked and related receptors. .

Relevance

EPHR and ephrins can act as both tumor suppressors and tumor enhancers depending on the context[8].

Structural highlights

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).

Ephrin A3 receptor with peptide substrate, nucleotide derivative and Mg+2 ion. Water molecules are shown as red spheres.

Nucleotide derivative and Mg+2 ion binding site.

Peptide substrate binding site (3fxx).[9]

3D Structures of ephrin receptor

Ephrin receptor 3D structures


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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