Ephrin type-A receptor 1

Function

Receptor tyrosine kinase which binds promiscuously membrane-bound 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. Binds with a low affinity EFNA3 and EFNA4 and with a high affinity to EFNA1 which most probably constitutes its cognate/functional ligand. Upon activation by EFNA1 induces cell attachment to the extracellular matrix inhibiting cell spreading and motility through regulation of ILK and downstream RHOA and RAC. Also plays a role in angiogenesis and regulates cell proliferation. May play a role in apoptosis.

Classification

Family (Pfam)

PF14575 EphA2_TM, PF25599 Ephrin_CRD, PF01404 Ephrin_lbd, PF07699 Ephrin_rec_like, PF00041 fn3, PF07714 PK_Tyr_Ser-Thr, PF00536 SAM_1

InterPro

Eph_TM, EphA1_rcpt_lig-bd, Ephrin_rcpt_lig-bd_dom, Ephrin_rcpt_TKs, FN3_dom, FN3_sf, Galactose-bd-like_sf, Growth_fac_rcpt_cys_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-kin_ephrin_A/B_rcpt-like, Tyr_kinase_AS, Tyr_kinase_cat_dom, Tyr_kinase_ephrin_rcpt, Tyr_kinase_rcpt_V_CS

Functional cluster

Secreted Growth Factors & Cytokines

Experimental structures · PDB · 4

• 2K1K NMR
• 2K1L NMR
• 3HIL X-ray 2.00A
• 3KKA X-ray 2.40A

A predicted model is available from AlphaFold.

Gene Ontology · 16

• GO:0005886 plasma membrane
• GO:0043235 receptor complex
• GO:0005524 ATP binding
• GO:0005003 ephrin receptor activity
• GO:0001968 fibronectin binding
• GO:0019901 protein kinase binding
• GO:0004714 transmembrane receptor protein tyrosine kinase activity
• GO:0005005 transmembrane-ephrin receptor activity
• GO:0001525 angiogenesis
• GO:0007169 cell surface receptor protein tyrosine kinase signaling pathway
• GO:0030336 negative regulation of cell migration
• GO:0045766 positive regulation of angiogenesis
• GO:0030335 positive regulation of cell migration
• GO:0001954 positive regulation of cell-matrix adhesion
• GO:0051496 positive regulation of stress fiber assembly
• GO:0034446 substrate adhesion-dependent cell spreading

Drugs targeting this protein · 1

• VANDETANIB inhibitor

Related proteins · sequence + function similarity

• Ephrin type-A receptor 1 0.98
• Ephrin type-B receptor 6 0.93
• Ephrin type-B receptor 6 0.93
• Ephrin type-B receptor 6 0.92
• Ephrin type-B receptor 6 0.92
• Ephrin type-B receptor 4 0.90
• Ephrin type-B receptor 4 0.89
• Ephrin type-A receptor 10 0.88
• Ephrin type-A receptor 10 0.88
• Tyrosine-protein kinase receptor UFO 0.86
• Tyrosine-protein kinase receptor TYRO3 0.85
• Tyrosine-protein kinase receptor TYRO3 0.85

Co-cited proteins · studied together in the literature

• Scaffold protein ILK 1 shared papers
• Protein-tyrosine kinase 2-beta 1 shared papers
• Tyrosine-protein kinase Lck 1 shared papers
• E3 ubiquitin-protein ligase TRIM52 1 shared papers
• Focal adhesion kinase 1 1 shared papers
• Ephrin type-A receptor 7 1 shared papers
• Ephrin type-B receptor 3 1 shared papers
• G protein-coupled receptor kinase 3 1 shared papers
• Ephrin type-B receptor 1 2 shared papers
• Ephrin type-B receptor 4 2 shared papers
• Ephrin type-A receptor 5 1 shared papers
• Ephrin type-A receptor 3 1 shared papers

Literature · 15 cited papers

• System-wide temporal characterization of the proteome and phosphoproteome of human embryonic stem cell differentiation. Sci. Signal. · 2011
• Development and validation of a method for profiling post-translational modification activities using protein microarrays. PLoS ONE · 2010
• EphA1 receptor silencing by small interfering RNA has antiangiogenic and antitumor efficacy in hepatocellular carcinoma. Oncol. Rep. · 2010
• Large-scale proteomics analysis of the human kinome. Mol. Cell. Proteomics · 2009
• EphA1 interacts with integrin-linked kinase and regulates cell morphology and motility. J. Cell Sci. · 2009
• Spatial structure and pH-dependent conformational diversity of dimeric transmembrane domain of the receptor tyrosine kinase EphA1. J. Biol. Chem. · 2008
• Novel splice variants derived from the receptor tyrosine kinase superfamily are potential therapeutics for rheumatoid arthritis. Arthritis Res. Ther. · 2008
• Ephrin-A1 stimulates migration of CD8+CCR7+ T lymphocytes. Eur. J. Immunol. · 2007
• Patterns of somatic mutation in human cancer genomes. Nature · 2007
• The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC). Genome Res. · 2004
• The DNA sequence of human chromosome 7. Nature · 2003
• Human chromosome 7: DNA sequence and biology. Science · 2003
• … and 3 more in the literature graph