Anthrax toxin receptor 1 and 2 (ANTXR1 and ANTXR2)

Anthrax toxin receptors 1 (ANTXR1, also known as TEM8) and 2 (ANTXR2, also known as CMG2) are type I transmembrane proteins that function as the primary cell surface anchors for the anthrax toxin secreted by Bacillus anthracis (Bradley et al., 2001; Scobie et al., 2003). Both receptors possess an extracellular von Willebrand factor type A (vWA) domain that mediates high-affinity binding to the Protective Antigen (PA) component of the toxin (UniProt P58335, Q9H6X2). Upon binding, the receptor-toxin complex is internalized via endocytosis, leading to the delivery of lethal and edema factors into the host cell cytoplasm, which causes systemic toxicity (PubMed: 12624192). Beyond their role in infection, ANTXR1 is significantly upregulated in tumor vasculature and plays a role in pathological angiogenesis (St Croix et al., 2000). ANTXR2 is essential for extracellular matrix homeostasis and is linked to hyaline fibromatosis syndrome when mutated (NIH). Therapeutic interventions include monoclonal antibodies like Raxibacumab and Obiltoxaximab, which neutralize PA to prevent receptor interaction (FDA). Experimental agents are also being developed to target ANTXR1 specifically for cancer therapy due to its expression in tumor-associated endothelium (PubMed: 27054418).

Other names

Tumor endothelial marker 8Capillary morphogenesis gene 2TEM8CMG2ANTXR1ANTXR2ATRHFS

Neutralization of Protective Antigen (PA) to prevent receptor binding and subsequent toxin internalization; targeted inhibition of tumor angiogenesis via ANTXR1 blockade.