Ephrin type-A receptor 8

Function

Receptor tyrosine kinase which binds promiscuously GPI-anchored ephrin-A 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. The GPI-anchored ephrin-A EFNA2, EFNA3, and EFNA5 are able to activate EPHA8 through phosphorylation. With EFNA5 may regulate integrin-mediated cell adhesion and migration on fibronectin substrate but also neurite outgrowth. During development of the nervous system also plays a role in axon guidance. Downstream effectors of the EPHA8 signaling pathway include FYN which promotes cell adhesion upon activation by EPHA8 and the MAP kinases in the stimulation of neurite outgrowth (By similarity).

Classification

Family (Pfam)

PF14575 EphA2_TM, PF25599 Ephrin_CRD, PF01404 Ephrin_lbd, PF00041 fn3, PF07714 PK_Tyr_Ser-Thr, PF00536 SAM_1

InterPro

Eph_TM, Ephrin_rcpt_lig-bd_dom, Ephrin_rcpt_TKs, FN3_dom, FN3_sf, Galactose-bd-like_sf, Ig-like_fold, Kinase-like_dom_sf, Prot_kinase_dom, Protein_kinase_ATP_BS, SAM, SAM/pointed_sf, Ser-Thr/Tyr_kinase_cat_dom, Tyr_kinase_AS, Tyr_kinase_cat_dom, Tyr_kinase_ephrin_rcpt, Tyr_kinase_rcpt_V_CS

Functional cluster

Immunoglobulin-Domain Cell Adhesion Proteins

Experimental structures · PDB · 3

• 1UCV NMR
• 1X5L NMR
• 3KUL X-ray 2.15A

A predicted model is available from AlphaFold.

Gene Ontology · 19

• GO:0030425 dendrite
• GO:0031901 early endosome membrane
• GO:0043005 neuron projection
• GO:0005886 plasma membrane
• GO:0005524 ATP binding
• GO:0005003 ephrin receptor activity
• GO:0005004 GPI-linked ephrin receptor activity
• GO:0019838 growth factor binding
• GO:0005005 transmembrane-ephrin receptor activity
• GO:0007411 axon guidance
• GO:0007155 cell adhesion
• GO:0048013 ephrin receptor signaling pathway
• GO:0031175 neuron projection development
• GO:0016322 neuron remodeling
• GO:0043410 positive regulation of MAPK cascade
• GO:0051897 positive regulation of phosphatidylinositol 3-kinase/protein kinase B signal transduction
• GO:0030155 regulation of cell adhesion
• GO:0033628 regulation of cell adhesion mediated by integrin
• GO:0006929 substrate-dependent cell migration

Drugs targeting this protein · 1

• VANDETANIB inhibitor

Related proteins · sequence + function similarity

• Ephrin type-A receptor 8 0.99
• Ephrin type-B receptor 4 0.95
• Ephrin type-B receptor 4 0.94
• Ephrin type-B receptor 3 0.94
• Ephrin type-B receptor 3 0.94
• Ephrin type-B receptor 4b 0.89
• Ephrin type-A receptor 3 0.89
• Ephrin type-A receptor 2 0.88
• Ephrin type-A receptor 2 0.88
• Ephrin type-B receptor 4a 0.87
• Ephrin type-A receptor 5 0.86
• Ephrin type-A receptor 5 0.86

Co-cited proteins · studied together in the literature

• Ephrin type-A receptor 8 4 shared papers
• Ephrin type-A receptor 8 1 shared papers
• Ephrin type-B receptor 2 2 shared papers
• Rho guanine nucleotide exchange factor TIAM1 1 shared papers
• Ankyrin repeat and sterile alpha motif domain-containing protein 1B 1 shared papers
• Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit gamma isoform 1 shared papers
• Ankyrin repeat and SAM domain-containing protein 1A 1 shared papers
• Ankyrin repeat and SAM domain-containing protein 1A 1 shared papers
• Ankyrin repeat and sterile alpha motif domain-containing protein 1B 1 shared papers
• Rho guanine nucleotide exchange factor TIAM1 1 shared papers
• Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit gamma isoform 1 shared papers
• Tyrosine-protein kinase Fyn 1 shared papers

Literature · 10 cited papers

• EphA8-ephrinA5 signaling and clathrin-mediated endocytosis is regulated by Tiam-1, a Rac-specific guanine nucleotide exchange factor. Mol. Cells · 2010
• Identification of phosphotyrosine binding domain-containing proteins as novel downstream targets of the EphA8 signaling function. Mol. Cell. Biol. · 2007
• Patterns of somatic mutation in human cancer genomes. Nature · 2007
• The DNA sequence and biological annotation of human chromosome 1. Nature · 2006
• The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC). Genome Res. · 2004
• The EphA8 receptor regulates integrin activity through p110gamma phosphatidylinositol-3 kinase in a tyrosine kinase activity-independent manner. Mol. Cell. Biol. · 2001
• Prediction of the coding sequences of unidentified human genes. XVII. The complete sequences of 100 new cDNA clones from brain which code for large proteins in vitro. DNA Res. · 2000
• Phosphorylation at Tyr-838 in the kinase domain of EphA8 modulates Fyn binding to the Tyr-615 site by enhancing tyrosine kinase activity. Oncogene · 1999
• Unified nomenclature for Eph family receptors and their ligands, the ephrins. Cell · 1997
• eek and erk, new members of the eph subclass of receptor protein-tyrosine kinases. Oncogene · 1991