Semaphorin-4A (SEMA4A)

Semaphorin-4A (SEMA4A) is a single-pass transmembrane protein belonging to the semaphorin family, originally described as an axon guidance molecule but now recognized for its roles in regulating immune responses, angiogenesis, and organ morphogenesis[1][4]. It is expressed on endothelial cells, immune cells (notably T cells), and retinal pigment epithelial cells[1][2][3]. SEMA4A interacts with several receptors—primarily Plexin-D1 on endothelial cells, T-cell immunoglobulin and mucin domain-containing protein 2 (Tim-2) on T cells, and Neuropilin-1 on regulatory T cells—to mediate its diverse effects[3]. In the immune system, SEMA4A drives the activation, stability, and differentiation of T cells, contributing to inflammatory and anti-tumor responses[1][3]. It negatively regulates angiogenesis by inhibiting VEGF-induced endothelial cell migration and proliferation[1]. In the retina, SEMA4A is essential for photoreceptor survival, regulating the intracellular trafficking and secretion of essential survival factors; mutations in SEMA4A cause retinal degenerative diseases[2]. Its functions as a ligand, interacting with various receptors, and its involvement in pathological conditions make it a validated therapeutic target and biomarker for certain immune, vascular, and retinal diseases[1][2][3].

Other names

Semaphorin-4ASEMA4ASEMABSEMBUNQ783/PRO1317Sema BSemBFLJ12287CORD10RP35semaphorin-Bsemaphorin-4Asema B

Drugs targeting Sema4A could act as agonists to stimulate immune responses or antagonists to inhibit angiogenesis