Homer scaffold protein 3 (HOMER3)

Homer scaffold protein 3 (HOMER3) is a multifunctional adaptor protein primarily found in the postsynaptic density of neuronal cells. It contains an N-terminal EVH1 (Enabled/vasodilator-stimulated phosphoprotein homology 1) domain for specific protein-protein interactions, and a C-terminal coiled-coil region with leucine zipper motifs for oligomerization[1][2][3][4]. HOMER3 acts as a molecular scaffold by linking group I metabotropic glutamate receptors (GRM1/mGluR1 and GRM5/mGluR5), inositol 1,4,5-trisphosphate (IP3) receptors, ryanodine receptors, Shank family proteins, and other cytoskeletal or signaling proteins, facilitating coupling between surface receptor activation and intracellular calcium release[1][2][3][4][5]. Beyond the nervous system, HOMER3 has roles in the immune system—negatively regulating T-cell activation via modulation of the calcineurin-NFAT pathway—and is involved in trafficking of amyloid precursor proteins and coordinating cytoskeletal organization[1][3]. In disease, HOMER3 has been associated with neurological disorders (such as spinocerebellar ataxia and familial hemiplegic migraine), as well as with cancer, where altered expression contributes to tumor aggressiveness and invasiveness[1][3]. Multiple transcript variants exist due to alternative splicing. While crucial for cellular organization and signal transduction, HOMER3 itself is not a traditional therapeutic target such as a receptor or enzyme, and no drugs are documented to target it directly[1][3].

Other names

Homer protein homolog 3Homer-3VESL3HOMER-3homer scaffolding protein 3homer homolog 3HOMER3Homerneuronal immediate early gene 3