Activin A receptor, type I (ACVR1) also known as ALK-2 is a protein

Protein

Proteins are biochemical compounds consisting of one or more polypeptides typically folded into a globular or fibrous form, facilitating a biological function. A polypeptide is a single linear polymer chain of amino acids bonded together by peptide bonds between the carboxyl and amino groups of...

 which in humans is encoded by the ACVR1 gene

Gene

A gene is a molecular unit of heredity of a living organism. It is a name given to some stretches of DNA and RNA that code for a type of protein or for an RNA chain that has a function in the organism. Living beings depend on genes, as they specify all proteins and functional RNA chains...

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Function

Activins are dimeric growth and differentiation factors which belong to the transforming growth factor-beta (TGF beta

TGF beta

Transforming growth factor beta is a protein that controls proliferation, cellular differentiation, and other functions in most cells. It plays a role in immunity, cancer, heart disease, diabetes, Marfan syndrome, and Loeys–Dietz syndrome....

) 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 BMP

Bone morphogenetic protein

Bone morphogenetic proteins are a group of growth factors also known as cytokines and as metabologens . Originally discovered by their ability to induce the formation of bone and cartilage, BMPs are now considered to constitute a group of pivotal morphogenetic signals, orchestrating tissue...

s. BMPs bind either ACVR2A

ACVR2A

Activin receptor type-2A is a protein that in humans is encoded by the ACVR2A gene.ACVR2A is an activin type 2 receptor.-Interactions:ACVR2A has been shown to interact with INHBA, SYNJ2BP and ACVR1B.-Further reading:...

/ACVR2B

ACVR2B

Activin receptor type-2B is a protein that in humans is encoded by the ACVR2B gene. ACVR2B is an activin type 2 receptor.-Interactions:ACVR2B has been shown to interact with SYNJ2BP and ACVR1B.-Further reading:...

 or a BMPR2

BMPR2

Bone morphogenetic protein receptor type II or BMPR2 is a serine/threonine receptor kinase. It binds Bone morphogenetic proteins, members of the TGF beta superfamily of ligands. BMPs are involved in a host of cellular functions including osteogenesis, cell growth and cell differentiation. Signaling...

 and then form a complex with ACVR1. These go on to recruit the R-SMAD

R-SMAD

R-SMAD stands for receptor-regulated SMAD. Smads are transcription factors that transduce extracellular TGF-ß superfamily ligand signaling from cell membrane bound TGF-ß receptors into the nucleus where they activate transcription TGF-ß target genes...

s SMAD1, SMAD2, SMAD3 or SMAD6.

Clinical significance

Mutations in the ACVR1 are associated with fibrodysplasia ossificans progressiva

Fibrodysplasia ossificans progressiva

Fibrodysplasia ossificans progressiva , sometimes referred to as Stone Man Syndrome, is an extremely rare disease of the connective tissue. A mutation of the body's repair mechanism causes fibrous tissue to be ossified when damaged. In many cases, injuries can cause joints to become permanently...

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