ACVR1
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Activin A receptor, type I (ACVR1) also known as ALK-2 is a protein which in humans is encoded by the ACVR1 gene.[1]
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Contents
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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.[2]
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.[3]
Clinical significance
A mutation in the gene ACVR1 (= ALK2) is responsible for the fibrodysplasia ossificans progressiva.[4] 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.[5] This causes endothelial cells to transform to mesenchymal stem cells and then to bone.[6]
References
- ^ ten Dijke P, Ichijo H, Franzén P, Schulz P, Saras J, Toyoshima H, Heldin CH, Miyazono K (October 1993). "Activin receptor-like kinases: a novel subclass of cell-surface receptors with predicted serine/threonine kinase activity". Oncogene 8 (10): 2879–87. PMID 8397373.
- ^ "Entrez Gene: ACVR1 (activin A receptor, type I)". http://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=90.
- ^ Inman GJ, Nicolás FJ, Callahan JF, Harling JD, Gaster LM, Reith AD, Laping NJ, Hill CS (July 2002). "SB-431542 is a potent and specific inhibitor of transforming growth factor-beta superfamily type I activin receptor-like kinase (ALK) receptors ALK4, ALK5, and ALK7". Molecular Pharmacology 62 (1): 65–74. doi:10.1124/mol.62.1.65. PMID 12065756.
- ^ Shore EM, Xu M, Feldman GJ et al (2006). "A recurrent mutation in the BMP type I receptor ACVR1 causes inherited and sporadic fibrodysplasia ossificans progressiva". Nat. Genet. 38 (5): 525–527. doi:10.1038/ng1783. PMID 16642017. http://www.nature.com/ng/journal/v38/n5/abs/ng1783.html.
- ^ News Release of FOP's Cause
- ^ Dinther et al (2010). "ALK2 R206H mutation linked to fibrodysplasia ossificans progressiva confers constitutive activity to the BMP type I receptor and sensitizes mesenchymal cells to BMP-induced osteoblast differentiation and bone formation". Journal of Bone and Mineral Research: 091211115834058–35. doi:10.1359/jbmr.091110.
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