SEMA4A Recombinant Rabbit mAb (S-4494-35)

SEMA4A (Semaphorin 4A, also known as Semaphorin-B) is a type I transmembrane protein belonging to the class 4 semaphorin family. The human gene is located at chromosome 1q22, and its extracellular region contains an N-terminal Sema domain, a PSI domain, and an immunoglobulin-like C2-type domain; through the Sema domain it binds receptors such as Plexin B1, Plexin B2, Plexin D1, and Tim-2 to mediate intercellular signaling. Because it is expressed in immune cells, SEMA4A is classified as an "immune semaphorin" and plays a key costimulatory role in T cell–dendritic cell interactions: it promotes antigen-specific T cell priming, T helper 1 (Th1) differentiation, and T-bet expression, and Sema4A-deficient mice show impaired T cell priming and defective Th1 responses. In addition, SEMA4A activates mTORC1 signaling through the Plexin B2 receptor and is indispensable for optimal activation of CD8⁺ T cells and production of effector molecules such as granzyme B and perforin. In vascular biology, SEMA4A can inhibit VEGF-mediated endothelial cell migration and proliferation as well as angiogenesis in vivo. In clinical genetics, pathogenic mutations in SEMA4A are associated with retinitis pigmentosa type 35 (RP35) and cone-rod dystrophy type 10 (CORD10). Recent studies have also revealed a protective role for SEMA4A in skeletal muscle homeostasis—it inhibits FoxO3a nuclear translocation and reactivates the PI3K-AKT-mTOR anabolic pathway through Plexin B2, thereby alleviating glucocorticoid-induced muscle atrophy and promoting injury repair. In the tumor field, the role of SEMA4A is context-dependent: in non-small cell lung cancer, tumor-derived SEMA4A can enhance CD8⁺ T cell cytotoxicity and improve the efficacy of PD-1 blockade, whereas in prostate and breast cancers it has been reported to be associated with progression. Notably, human SEMA4A and mouse Sema4A differ functionally across species: human SEMA4A is preferentially expressed on antigen-presenting cells and costimulates CD4⁺ T cells by binding the ILT-4 receptor to drive Th2 responses, whereas mouse Sema4A mainly drives Th1 responses through Tim-2.