EPS8L2 Gene: Function, Expression, and Disease Associations

EPS8L2 (EPS8 like 2) is a protein-coding gene that belongs to the EPS8 family of signaling adaptors. The encoded protein contains an N-terminal phosphotyrosine-binding (PTB) domain, a central SH3 domain, and a C-terminal sterile alpha motif (SAM) domain. It functions as a regulator of actin cytoskeleton dynamics by modulating the activity of the actin-capping protein complex and participates in receptor tyrosine kinase signaling, particularly downstream of EGFR. EPS8L2 is involved in cell migration, proliferation, and endocytosis.

Tissue Expression

Cell Line Expression

Hotspot Mutations

Mutation functional classification

• EGFR signaling pathway (Reactome: R-HSA-177929)

• Actin nucleation by ARP-WASP complex (Reactome: R-HSA-5663213)

• Regulation of actin dynamics for phagocytic cup formation (Reactome: R-HSA-2029481)

The EPS8L2 protein (UniProt Q9H6S3) is a 715-amino-acid adaptor molecule that localizes to the cytoplasm and cell cortex. It contains a PTB domain (residues 1-120), an SH3 domain (residues 200-260), and a SAM domain (residues 600-660). Through its SH3 domain, it interacts with EPS8 and ABI1 to form a complex that regulates actin capping. The PTB domain mediates binding to phosphotyrosine residues on activated receptors such as EGFR. EPS8L2 is essential for normal hearing, as it maintains the precise actin architecture of stereocilia in inner ear hair cells.