EFNB3
Description
The EFNB3 (ephrin B3) is a protein-coding gene located on chromosome 17.
EFNB3 is a protein encoded by the EFNB3 gene in humans. It belongs to the ephrin gene family, which plays a vital role in brain development and maintenance. The EPH and EPH-related receptors constitute the largest subfamily of receptor protein-tyrosine kinases, characterized by a single kinase domain and an extracellular region with a cysteine-rich domain and two fibronectin type III repeats. The ephrin ligands and receptors are classified into two groups: ephrin-A (EFNA) and ephrin-B (EFNB), based on their structures and sequence relationships. EFNA proteins are anchored to the membrane by a glycosylphosphatidylinositol linkage, while EFNB proteins are transmembrane proteins. EFNB ligands contain an intracellular tail with highly conserved tyrosine residues and a PDZ-binding motif at the C-terminus. This tail enables reverse signaling, where signaling occurs in the ligand-containing cell, rather than the receptor-containing cell. Upon receptor-ligand interaction, tyrosine residues become phosphorylated, leading to the recruitment of PDZ domain-containing proteins. The Eph family of receptors is similarly divided into two groups based on the similarity of their extracellular domain sequences and their affinity for binding ephrin-A and ephrin-B ligands.
EFNB3 is a cell surface transmembrane ligand that interacts with Eph receptors, a family of receptor tyrosine kinases essential for cell migration, repulsion, and adhesion during neuronal, vascular, and epithelial development. EFNB3 binds promiscuously to Eph receptors on neighboring cells, initiating bidirectional signaling through contact-dependent mechanisms. This signaling process, known as forward signaling, occurs downstream of the Eph receptor, while reverse signaling takes place downstream of the EFNB3 ligand. EFNB3 is thought to play a crucial role in forebrain function. In vitro studies have demonstrated its ability to bind to and induce the collapse of commissural axons/growth cones, suggesting a potential role in guiding axon projections. Additionally, EFNB3 may contribute to the alignment of longitudinally projecting axons.
EFNB3 is also known as EFL6, EPLG8, LERK8.
Associated Diseases
- spinocerebellar ataxia type 23
- spinocerebellar ataxia type 35
- episodic ataxia type 5
- spinocerebellar ataxia type 15/16
- early-onset generalized limb-onset dystonia
- hereditary spastic paraplegia 72
- ataxia - deafness - intellectual disability syndrome
- spinocerebellar ataxia type 4
- spinocerebellar ataxia type 20
- episodic ataxia type 8
- urocanic aciduria
