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.
For more details see Ephrin Type-A Receptor and Kinase-linked, enzyme-linked and related receptors.
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Relevance
EPHR and ephrins can act as both tumor suppressors and tumor enhancers depending on the context[6].
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).[7]
3D Structures of ephrin receptor
Ephrin receptor 3D structures
- ↑ 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:https://dx.doi.org/10.1101/gad.1973910
- ↑ 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
- ↑ 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
- ↑ 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
- ↑ 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
- ↑ 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:https://dx.doi.org/10.1016/j.ceb.2010.08.005
- ↑ 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:https://dx.doi.org/10.1111/j.1742-4658.2009.07147.x
