ACVR1 Protein, Canine (HEK293, His)

Activin A receptor type I (ACVR1) gene, also known as ALK-2, is located in chromosome 2q23-q24 and encodes for the 509 amino acid protein. The ACVR1 protein product is initially described as an activin type I receptor, and it is found to be expressed in several tissues and different human cell lines^[1].
The sequence of amino acids in ACVR1 proteins from different species is very stable, which leads to the conclusion that in the process of evolution, ACVR1 has been only slightly altered, and that both in humans and in animals, its function is similar.
As a member of the BMP/TGFβ receptor family, the ACVR1 protein contains an extracellular N-terminal ligand-binding domain, a transmembrane (TM) domain, an intracellular glycine-serine-rich (GS) domain, and a protein kinase (PK) domain. The loop positioned in the helix-loop-helix of the GS domain contains the key residues responsible for ACVR1 activation upon phosphorylation. As a type I receptor, ACVR1 forms heterotetrameric receptor complexes with the type II receptors BMPR2, ACVR2A, and ACVR2B. Such complexes consist of two type I and two type II receptors. Upon binding of ligands to the heteromeric complexes, type II receptors transphosphorylate the GS domain of type I receptors. As a result, the kinase domain of type I receptors is activated and subsequently phosphorylates SMAD1/5/8 proteins that transduce the signal. ACVR1 is first described to bind to activin A, a member of the BMP/TGFβ family that usually triggers phosphorylation and activation of SMAD2/3 upon complex formation with type II receptors. Later, ACVR1 is also found to bind several BMPs with distinct affinities, triggering SMAD1/5/8 signalling. Besides canonical SMAD signalling, ACVR1 can activate non-canonical signalling pathways, such as p38 mitogen-activated protein kinases/MAPKs^[1].
ACVR1 is involved in a wide variety of biological processes, including bone, heart, cartilage, nervous, and reproductive system development and regulation. Moreover, ACVR1 has been extensively studied for its causal role in fibrodysplasia ossificans progressiva (FOP). ACVR1 is linked to different pathologies, including cardiac malformations and alterations in the reproductive system. More recently, ACVR1 has been experimentally validated as a cancer driver gene in diffuse intrinsic pontine glioma (DIPG)^[1].

Recombinant human ACVR1 (2.5-5 μg/mL) robustly down-regulates phosphorylated Smad1/5/8 and p38 MAPK levels in the HUVEC^R26H cells. ACVR1 also inhibits chondro-osseous differentiation in HUVEC^R26H cells^[2].