Download Gene Section ACVR2A (activin A receptor, type IIA) in Oncology and Haematology

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Gene Section
Short Communication
ACVR2A (activin A receptor, type IIA)
Jessica Bauer, Sarah Boles, Eddy Chau, Barbara Jung
Department of Medicine, Division of Gastroenterology, Northwestern University, Chicago 303 East Superior
Street, IL, 60611, USA (JB, BJ), Division of Gastroenterology, University of California, San Diego 9500
Gilman Drive 0063 La Jolla, CA, 92093-0063, USA (SB), Division of Gastroenterology, University of
California, San Diego 9500 Gilman Drive 0063 La Jolla, CA, 92093-0063, USA (EC)
Published in Atlas Database: May 2012
Online updated version : http://AtlasGeneticsOncology.org/Genes/ACVR2ID567ch2q22.html
DOI: 10.4267/2042/48146
This article is an update of :
Boles S, Chau E, Jung B. ACVR2A (Activin Receptor Type 2). Atlas Genet Cytogenet Oncol Haematol 2008;12(1):1-2.
This work is licensed under a Creative Commons Attribution-Noncommercial-No Derivative Works 2.0 France Licence.
© 2012 Atlas of Genetics and Cytogenetics in Oncology and Haematology
receptor for activin, with a cysteine-rich extracellular
ligand-binding domain, a single pass transmembrane
domain, and an intracellular domain with constitutive
serine/threonine kinase activity.
Upon binding activin, ACVR2 associates with and
phosphorylates ACVR1.
ACVR1, in turn, phosphorylates Smad2 and/or Smad3.
Phosphorylated Smad2 and Smad3 associate with
Smad4, translocate to the nucleus, and regulate gene
expression.
There may be other non-Smad pathways in activin
signal transduction. These include the RhoA-ROCKMEKK1-JNK and MEKK1-p38 pathways.
In addition to activin, other ligands such as myostatin,
nodal, and bone morphogenetic protein 7 (BMP-7) may
also bind to ACVR2 and affect signal transduction.
Identity
Other names: ACVR2, ACTRII, ACTR-IIA,
ACTRIIA
HGNC (Hugo): ACVR2A
Local order: Genes flanking ACVR2A, in centromere
to telomere direction on 2q22, are:
- PABPCP2 (2q22.3) polyadenylate binding protein,
cytoplasmic, pseudogene 2.
- ACVR2 (2q22.3) activin receptor type IIA.
- ORC4L (2q23.1) origin recognition complex, subunit
4.
DNA/RNA
Description
Expression
ACVR2 gene spans a region of 85796 bp and has 11
exons. Exon lengths are 180, 208, 110, 155, 144, 144,
146, 115, 139, 131 and 3745 base pairs. Exon 10
contains a polyadenine tract that may be mutated in
microsatellite unstable cells.
Abundant expression in multiple tissues, including
skeletal muscle, stomach, heart, endometrium, testes,
prostate, ovary, and neural tissues. The cell surface
level of ACVR2 and ACVR2B is regulated by proteins
called ARIPs (activin receptor-interacting proteins).
Transcription
Localisation
The transcript is 5217 base pairs.
Cell surface, spanning cytoplasmic membrane.
Protein
Function
Activin signals via its receptors, ACVR1 and ACVR2,
and has roles in cell proliferation, differentiation,
apoptosis, metabolism, immune response, wound
repair, and endocrine function.
Description
ACVR2 is a member of the transforming growth factor
beta (TGF-β) receptor family. It is a 70-75kDa protein
consisting of 513 amino acids. It is a transmembrane
Atlas Genet Cytogenet Oncol Haematol. 2012; 16(10)
714
ACVR2A (activin A receptor, type IIA)
Bauer J, et al.
Attisano L, Wrana JL, Montalvo E, Massagué J. Activation of
signalling by the activin receptor complex. Mol Cell Biol. 1996
Mar;16(3):1066-73
Mutations
Germinal
Loss
of
heterozygosity
hypermethylation.
(LOH).
Jung B, Doctolero RT, Tajima A, Nguyen AK, Keku T, Sandler
RS, Carethers JM. Loss of activin receptor type 2 protein
expression in microsatellite unstable colon cancers.
Gastroenterology. 2004 Mar;126(3):654-9
Promoter
Somatic
Chen YG, Wang Q, Lin SL, Chang CD, Chuang J, Ying SY.
Activin signaling and its role in regulation of cell proliferation,
apoptosis, and carcinogenesis. Exp Biol Med (Maywood). 2006
May;231(5):534-44
Exon 10 polyadenine tract (A8-A7).
Implicated in
Jung B, Smith EJ, Doctolero RT, Gervaz P, Alonso JC, Miyai
K, Keku T, Sandler RS, Carethers JM. Influence of target gene
mutations on survival, stage and histology in sporadic
microsatellite unstable colon cancers. Int J Cancer. 2006 May
15;118(10):2509-13
Microsatellite unstable colon cancer
Note
Colon cancer with A8-A7 deletion in exon10.
Prognosis
Increased tumor size.
Abnormal protein
No fusion protein; truncated non-functional protein.
Oncogenesis
Occurs late in adenoma to carcinoma transition.
Liu ZH, Tsuchida K, Matsuzaki T, Bao YL, Kurisaki A, Sugino
H. Characterization of isoforms of activin receptor-interacting
protein 2 that augment activin signaling. J Endocrinol. 2006
May;189(2):409-21
Jung BH, Beck SE, Cabral J, Chau E, Cabrera BL, Fiorino A,
Smith EJ, Bocanegra M, Carethers JM. Activin type 2 receptor
restoration in MSI-H colon cancer suppresses growth and
enhances migration with activin. Gastroenterology. 2007
Feb;132(2):633-44
Microsatellite stable colon cancer
Fitzpatrick E, Johnson MP, Dyer TD, Forrest S, Elliott K,
Blangero J, Brennecke SP, Moses EK. Genetic association of
the activin A receptor gene (ACVR2A) and pre-eclampsia. Mol
Hum Reprod. 2009 Mar;15(3):195-204
Note
LOH and promoter hypermethylation.
Prognosis
Increased tumor size.
Abnormal protein
No fusion protein; truncated non-functional protein.
Oncogenesis
Occurs late in adenoma to carcinoma transition.
Jung B, Gomez J, Chau E, Cabral J, Lee JK, Anselm A, Slowik
P, Ream-Robinson D, Messer K, Sporn J, Shin SK, Boland
CR, Goel A, Carethers JM. Activin signaling in microsatellite
stable colon cancers is disrupted by a combination of genetic
and epigenetic mechanisms. PLoS One. 2009 Dec
14;4(12):e8308
Chung H, Chaudhry J, Lai JF, Young DJ, Carethers JM.
Flanking nucleotide specificity for DNA mismatch repairdeficient frameshifts within activin receptor 2 (ACVR2). Mutat
Res. 2012 Jan 3;729(1-2):73-80
References
Mathews LS, Vale WW. Characterization of type II activin
receptors. Binding, processing, and phosphorylation. J Biol
Chem. 1993 Sep 5;268(25):19013-8
This article should be referenced as such:
Bauer J, Boles S, Chau E, Jung B. ACVR2A (activin A
receptor, type IIA). Atlas Genet Cytogenet Oncol Haematol.
2012; 16(10):714-715.
Hildén K, Tuuri T, Erämaa M, Ritvos O. Expression of type II
activin receptor genes during differentiation of human K562
cells and cDNA cloning of the human type IIB activin receptor.
Blood. 1994 Apr 15;83(8):2163-70
Atlas Genet Cytogenet Oncol Haematol. 2012; 16(10)
715