Trisha Shetty

ACVR1

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Species  Human
Entrez  90
Human  Mouse
Ensembl  ENSG00000115170
ACVR1
Aliases  ACVR1, ACTRI, ACVR1A, ACVRLK2, ALK2, FOP, SKR1, TSRI, activin A receptor type 1
External IDs  OMIM: 102576 MGI: 87911 HomoloGene: 7 GeneCards: ACVR1

Activin A receptor, type I (ACVR1) is a protein which in humans is encoded by the ACVR1 gene; also known as ALK-2 (activin receptor-like kinase-2). ACVR1 has been linked to the 2q23-24 region of the genome. This protein is important in the bone morphogenic protein (BMP) pathway which is responsible for the development and repair of the skeletal system. While knock-out models with this gene are in progress, the ACVR1 gene has been connected to Fibrodysplasia Ossificans Progressiva, a disease characterized by the formation of heterotopic bone throughout the body.

Contents

Function

Activins are dimeric growth and differentiation factors which belong to the transforming growth factor-beta (TGF beta) superfamily of structurally related signaling proteins. Activins signal through a heteromeric complex of receptor serine kinases which include at least two type I ( I and IB) and two type II (II and IIB) receptors. These receptors are all transmembrane proteins, composed of a ligand-binding extracellular domain with cysteine-rich region, a transmembrane domain, and a cytoplasmic domain with predicted serine/threonine specificity. Type I receptors are essential for signaling; and type II receptors are required for binding ligands and for expression of type I receptors. Type I and II receptors form a stable complex after ligand binding, resulting in 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 ACVR2A/ACVR2B or a BMPR2 and then form a complex with ACVR1. These go on to recruit the R-SMADs SMAD1, SMAD2, SMAD3 or SMAD6.

Clinical significance

A mutation in the gene ACVR1 (= ALK2) is responsible for the fibrodysplasia ossificans progressiva. ACVR1 encodes 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 the protein ALK2 to change in the critical glycine-serine activation domain of the protein which will cause the protein to bind its inhibitory ligand (FKBP12) less tightly, and activate its SMAD pathway specific proteins more effectively than usual. The result is the BMP pathway will trigger when it should not, and bone will form in soft tissues throughout the body. This causes endothelial cells to transform to mesenchymal stem cells and then to bone.

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

References

ACVR1 Wikipedia


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