ACVR1

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Activin A receptor, type I
Protein ACVR1 PDB 3H9R.png
Rendering based on PDB 3H9R.
Available structures
PDB Ortholog search: PDBe, RCSB
Identifiers
Symbols ACVR1 ; ACTRI; ACVR1A; ACVRLK2; ALK2; FOP; SKR1; TSRI
External IDs OMIM102576 MGI87911 HomoloGene7 ChEMBL: 5903 GeneCards: ACVR1 Gene
EC number 2.7.11.30
Orthologs
Species Human Mouse
Entrez 90 11477
Ensembl ENSG00000115170 ENSMUSG00000026836
UniProt Q04771 P37172
RefSeq (mRNA) NM_001105 NM_001110204
RefSeq (protein) NP_001096 NP_001103674
Location (UCSC) Chr 2:
158.59 – 158.73 Mb
Chr 2:
58.39 – 58.57 Mb
PubMed search [1] [2]

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).[1]

Function[edit]

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[edit]

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[edit]

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]


Mutations in the ACVR1 gene have been linked to cancer, especially diffuse intrinsic pontine glioma (DIPG).[7][8][9]

See also "Shared Mutation for Two Childhood Diseases" http://jnci.oxfordjournals.org/content/106/7/dju222.full

References[edit]

  1. ^ 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. 
  2. ^ "Entrez Gene: ACVR1 (activin A receptor, type I)". 
  3. ^ 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. 
  4. ^ 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. 
  5. ^ News Release of FOP's Cause
  6. ^ 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. 
  7. ^ Taylor, K. R.; MacKay, A; Truffaux, N; Butterfield, Y. S.; Morozova, O; Philippe, C; Castel, D; Grasso, C. S.; Vinci, M; Carvalho, D; Carcaboso, A. M.; De Torres, C; Cruz, O; Mora, J; Entz-Werle, N; Ingram, W. J.; Monje, M; Hargrave, D; Bullock, A. N.; Puget, S; Yip, S; Jones, C; Grill, J (2014). "Recurrent activating ACVR1 mutations in diffuse intrinsic pontine glioma". Nature Genetics 46 (5): 457–61. doi:10.1038/ng.2925. PMC 4018681. PMID 24705252.  edit
  8. ^ "Cure Brain Cancer - News - Multiple Breakthroughs in Childhood Brain Cancer DIPG". Cure Brain Cancer Foundation. 
  9. ^ Buczkowicz P, Hoeman C, Rakopoulos P, Pajovic S, Letourneau L, Dzamba M, Morrison A, Lewis P, Bouffet E, Bartels U, Zuccaro J, Agnihotri S, Ryall S, Barszczyk M, Chornenkyy Y, Bourgey M, Bourque G, Montpetit A, Cordero F, Castelo-Branco P, Mangerel J, Tabori U, Ho KC, Huang A, Taylor KR, Mackay A, Bendel AE, Nazarian J, Fangusaro JR, Karajannis MA, Zagzag D, Foreman NK, Donson A, Hegert JV, Smith A, Chan J, Lafay-Cousin L, Dunn S, Hukin J, Dunham C, Scheinemann K, Michaud J, Zelcer S, Ramsay D, Cain J, Brennan C, Souweidane MM, Jones C, Allis CD, Brudno M, Becher O, Hawkins C (2014). "Genomic analysis of diffuse intrinsic pontine gliomas identifies three molecular subgroups and recurrent activating ACVR1 mutations". Nat. Genet. 46 (5): 451–6. doi:10.1038/ng.2936. PMID 24705254. 

This article incorporates text from the United States National Library of Medicine, which is in the public domain.