EFNA1

This gene encodes a member of the ephrin (EPH) family. The ephrins and EPH-related receptors comprise the largest subfamily of receptor protein-tyrosine kinases and have been implicated in mediating developmental events, especially in the nervous system and in erythropoiesis. Based on their structures and sequence relationships, ephrins are divided into the ephrin-A (EFNA) class, which are anchored to the membrane by a glycosylphosphatidylinositol linkage, and the ephrin-B (EFNB) class, which are transmembrane proteins. This gene encodes an EFNA class ephrin which binds to the EPHA2, EPHA4, EPHA5, EPHA6, and EPHA7 receptors. Two transcript variants that encode different isoforms were identified through sequence analysis. [provided by RefSeq, Jul 2008]

Full Name

Ephrin A1

Research Area

Cell surface GPI-bound ligand for Eph receptors, a family of receptor tyrosine kinases which are crucial for migration, repulsion and adhesion during neuronal, vascular and epithelial development. Binds promiscuously Eph receptors residing on adjacent cells, leading to contact-dependent bidirectional signaling into neighboring cells. Plays an important role in angiogenesis and tumor neovascularization. The recruitment of VAV2, VAV3 and PI3-kinase p85 subunit by phosphorylated EPHA2 is critical for EFNA1-induced RAC1 GTPase activation and vascular endothelial cell migration and assembly. Exerts anti-oncogenic effects in tumor cells through activation and down-regulation of EPHA2. Activates EPHA2 by inducing tyrosine phosphorylation which leads to its internalization and degradation. Acts as a negative regulator in the tumorigenesis of gliomas by down-regulating EPHA2 and FAK. Can evoke collapse of embryonic neuronal growth cone and regulates dendritic spine morphogenesis.

Biological Process

Angiogenesis Source: UniProtKB-KW
Aortic valve morphogenesis Source: BHF-UCL
Axon guidance Source: GO_Central
Cell-cell signaling Source: ProtInc
Cell migration Source: UniProtKB
Endocardial cushion to mesenchymal transition involved in heart valve formation Source: BHF-UCL
Ephrin receptor signaling pathway Source: UniProtKB
Mitral valve morphogenesis Source: BHF-UCL
Negative regulation of dendritic spine morphogenesis Source: UniProtKB
Negative regulation of epithelial to mesenchymal transition Source: BHF-UCL
Negative regulation of MAPK cascade Source: Ensembl
Negative regulation of proteolysis involved in cellular protein catabolic process Source: ARUK-UCL
Negative regulation of thymocyte apoptotic process Source: Ensembl
Negative regulation of transcription by RNA polymerase II Source: BHF-UCL
Notochord formation Source: Ensembl
Positive regulation of amyloid-beta formation Source: ARUK-UCL
Positive regulation of aspartic-type endopeptidase activity involved in amyloid precursor protein catabolic process Source: ARUK-UCL
Positive regulation of MAPK cascade Source: Ensembl
Positive regulation of peptidyl-tyrosine phosphorylation Source: UniProtKB
Positive regulation of protein phosphorylation Source: ARUK-UCL
Positive regulation of protein tyrosine kinase activity Source: ARUK-UCL
Protein stabilization Source: ARUK-UCL
Regulation of angiogenesis Source: Ensembl
Regulation of axonogenesis Source: Ensembl
Regulation of blood vessel endothelial cell migration Source: Ensembl
Regulation of cell adhesion mediated by integrin Source: UniProtKB
Regulation of peptidyl-tyrosine phosphorylation Source: UniProtKB
Substrate adhesion-dependent cell spreading Source: UniProtKB

Cellular Location

Cell membrane
Ephrin-A1, secreted form: Secreted

PTM

Undergoes proteolysis by a metalloprotease to give rise to a soluble monomeric form.
N-Glycosylation is required for binding to EPHA2 receptor and inducing its internalization.