Activin A Receptor Type 2A (ACTR-IIA)

ACVR2A, also known as Activin RIIA, is an activin type II receptor. On ligand binding, ACVR2A can forms a receptor complex consisting of two type II and two type I transmembrane serine/threonine kinases. ACVR2A is a receptor for Activin A, Activin B and Inhibin A.
The sequence of amino acids in ACVR2A proteins from different species is very stable, which leads to the conclusion that in the process of evolution, ACVR2A has been only slightly altered, and that both in humans and in animals, its function is similar.
Signaling by activins and BMPs is highly promiscuous, since apart from signaling through ALK4/7, the activin type II receptors (ACVR2A and 2B) can interact also with several type I BMP receptors (ALK1/2/3/6), which can also form complexes with the type II BMP receptor, BMPRII. Type II receptors phosphorylate and activate type I receptors which autophosphorylate, then bind and activate SMAD transcriptional regulators. ACVR2A can form complexes with different type I receptors that signal either to Smad2/3 (ALK4) or to Smad1/5/8 (ALK2, ALK3, ALK6). The different type I receptors compete for binding to ACVR2A and that this competition provides a mechanism that balances signaling between Activin A-mediated, ALK4-dependent Smad2/3 signaling, and BMP-mediated ALK2 or ALK3-dependent signaling to Smad1/5/8. In myeloma cells, BMP-6- and BMP-9-induced activation of SMAD1/5/8 through ACVR2A/ACVR2B/ALK2 is inhibited by activin A treatment[1][3].