ACVR1

From Wikipedia, the free encyclopedia
Jump to: navigation, search
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 IUPHAR: 1785 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]

References[edit]

  1. ^ ten Dijke P, Ichijo H, Franzén P, Schulz P, Saras J, Toyoshima H et al. (Oct 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 et al. (Jul 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, Fenstermacher DA, Cho TJ, Choi IH et al. (May 2006). "A recurrent mutation in the BMP type I receptor ACVR1 causes inherited and sporadic fibrodysplasia ossificans progressiva". Nature Genetics 38 (5): 525–527. doi:10.1038/ng1783. PMID 16642017. 
  5. ^ News Release of FOP's Cause
  6. ^ van Dinther M, Visser N, de Gorter DJ, Doorn J, Goumans MJ, de Boer J et al. (Jun 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 25 (6): 091211115834058–35. doi:10.1359/jbmr.091110. PMID 19929436. 
  7. ^ Taylor KR, Mackay A, Truffaux N, Butterfield YS, Morozova O, Philippe C et al. (May 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. 
  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 et al. (May 2014). "Genomic analysis of diffuse intrinsic pontine gliomas identifies three molecular subgroups and recurrent activating ACVR1 mutations". Nature Genetics 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.