ACVR1

Activin A receptor, type I (ACVR1) is a is_associated_with::protein which in humans is encoded by the ACVR1 is_associated_with::gene; also known as ALK-2 (activin receptor-like kinase-2).

Function
is_associated_with::Activins are dimeric growth and differentiation factors which belong to the transforming growth factor-beta (is_associated_with::TGF beta) superfamily of structurally related signaling proteins. Activins signal through a heteromeric complex of receptor is_associated_with::serine kinases which include at least two type I ( I and IB) and two type II (II and IIB) receptors. These receptors are all is_associated_with::transmembrane proteins, composed of a ligand-binding extracellular domain with cysteine-rich region, a is_associated_with::transmembrane domain, and a cytoplasmic domain with predicted is_associated_with::serine/is_associated_with::threonine specificity. Type I receptors are essential for signaling; and type II receptors are required for binding is_associated_with::ligands and for expression of type I receptors. Type I and II receptors form a stable complex after ligand binding, resulting in is_associated_with::phosphorylation of type I receptors by type II receptors. This gene encodes activin A type I receptor which signals a particular transcriptional response in concert with activin type II receptors.

Signaling
ACVR1 transduces signals of BMPs. BMPs bind either is_associated_with::ACVR2A/is_associated_with::ACVR2B or a is_associated_with::BMPR2 and then form a complex with ACVR1. These go on to recruit the is_associated_with::R-SMADs is_associated_with::SMAD1, is_associated_with::SMAD2, is_associated_with::SMAD3 or is_associated_with::SMAD6.

Clinical significance
A mutation in the gene ACVR1 (= ALK2) is responsible for the is_associated_with::fibrodysplasia ossificans progressiva. ACVR1 encodes is_associated_with::activin receptor type-1, a BMP type-1 receptor. The mutation causes the ACVR1 protein to have the amino acid histidine substituted for the amino acid arginine at position 206. This causes is_associated_with::endothelial cells to transform to is_associated_with::mesenchymal stem cells and then to bone.

Mutations in the ACVR1 gene have been linked to cancer, especially diffuse intrinsic pontine glioma(DIPG).