ACVR2A (Activin Receptor Type 2)
2012-05-01 Jessica Bauer  , Sarah Boles  , Eddy Chau  , Barbara Jung   AffiliationDNA/RNA
Description
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.
Transcription
The transcript is 5217 base pairs.
Proteins
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 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-ROCK-MEKK1-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.
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-ROCK-MEKK1-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.
Expression
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).
Localisation
Cell surface, spanning cytoplasmic membrane.
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.
Mutations
Germinal
Loss of heterozygosity (LOH). Promoter hypermethylation.
Somatic
Exon 10 polyadenine tract (A8-A7).
Implicated in
Entity name
Microsatellite unstable colon cancer
Note
Colon cancer with A8-A7 deletion in exon10.
Prognosis
Increased tumor size.
Fusion protein
No fusion protein; truncated non-functional protein.
Oncogenesis
Occurs late in adenoma to carcinoma transition.
Entity name
Microsatellite stable colon cancer
Note
LOH and promoter hypermethylation.
Prognosis
Increased tumor size.
Fusion protein
No fusion protein; truncated non-functional protein.
Oncogenesis
Occurs late in adenoma to carcinoma transition.
Article Bibliography
| Pubmed ID | Last Year | Title | Authors |
|---|---|---|---|
| 8622651 | 1996 | Activation of signalling by the activin receptor complex. | Attisano L et al |
| 16636301 | 2006 | Activin signaling and its role in regulation of cell proliferation, apoptosis, and carcinogenesis. | Chen YG et al |
| 22001236 | 2012 | Flanking nucleotide specificity for DNA mismatch repair-deficient frameshifts within activin receptor 2 (ACVR2). | Chung H et al |
| 19126782 | 2009 | Genetic association of the activin A receptor gene (ACVR2A) and pre-eclampsia. | Fitzpatrick E et al |
| 8161782 | 1994 | Expression of type II activin receptor genes during differentiation of human K562 cells and cDNA cloning of the human type IIB activin receptor. | Hildén K et al |
| 14988818 | 2004 | Loss of activin receptor type 2 protein expression in microsatellite unstable colon cancers. | Jung B et al |
| 20011542 | 2009 | Activin signaling in microsatellite stable colon cancers is disrupted by a combination of genetic and epigenetic mechanisms. | Jung B et al |
| 16380996 | 2006 | Influence of target gene mutations on survival, stage and histology in sporadic microsatellite unstable colon cancers. | Jung B et al |
| 17258738 | 2007 | Activin type 2 receptor restoration in MSI-H colon cancer suppresses growth and enhances migration with activin. | Jung BH et al |
| 16648306 | 2006 | Characterization of isoforms of activin receptor-interacting protein 2 that augment activin signaling. | Liu ZH et al |
| 8395525 | 1993 | Characterization of type II activin receptors. Binding, processing, and phosphorylation. | Mathews LS et al |
Other Information
Locus ID:
NCBI: 92
MIM: 102581
HGNC: 173
Ensembl: ENSG00000121989
Variants:
dbSNP: 92
ClinVar: 92
TCGA: ENSG00000121989
COSMIC: ACVR2A
RNA/Proteins
| Gene ID | Transcript ID | Uniprot |
|---|---|---|
| ENSG00000121989 | ENST00000241416 | P27037 |
| ENSG00000121989 | ENST00000404590 | P27037 |
| ENSG00000121989 | ENST00000535787 | P27037 |
Expression (GTEx)
Pathways
Protein levels (Protein atlas)
References
| Pubmed ID | Year | Title | Citations |
|---|---|---|---|
| 37378449 | 2023 | Activin A/ACVR2A axis inhibits epithelial-to-mesenchymal transition in colon cancer by activating SMAD2. | 1 |
| 37378449 | 2023 | Activin A/ACVR2A axis inhibits epithelial-to-mesenchymal transition in colon cancer by activating SMAD2. | 1 |
| 33420656 | 2021 | Activin a Receptor Type 2A Mutation Affects the Tumor Biology of Microsatellite Instability-High Gastric Cancer. | 1 |
| 33420656 | 2021 | Activin a Receptor Type 2A Mutation Affects the Tumor Biology of Microsatellite Instability-High Gastric Cancer. | 1 |
| 31790936 | 2020 | Association between ACVR2A gene polymorphisms and risk of hypertensive disorders of pregnancy in the northern Chinese population. | 2 |
| 31790936 | 2020 | Association between ACVR2A gene polymorphisms and risk of hypertensive disorders of pregnancy in the northern Chinese population. | 2 |
| 29506428 | 2019 | Targeted sequencing analysis of ACVR2A gene identifies novel risk variants associated with preeclampsia. | 5 |
| 30621627 | 2019 | Non-additive effects of ACVR2A in preeclampsia in a Philippine population. | 2 |
| 31273315 | 2019 | Synovial chondromatosis and soft tissue chondroma: extraosseous cartilaginous tumor defined by FN1 gene rearrangement. | 16 |
| 31315975 | 2019 | Structural characterization of an activin class ternary receptor complex reveals a third paradigm for receptor specificity. | 39 |
| 29506428 | 2019 | Targeted sequencing analysis of ACVR2A gene identifies novel risk variants associated with preeclampsia. | 5 |
| 30621627 | 2019 | Non-additive effects of ACVR2A in preeclampsia in a Philippine population. | 2 |
| 31273315 | 2019 | Synovial chondromatosis and soft tissue chondroma: extraosseous cartilaginous tumor defined by FN1 gene rearrangement. | 16 |
| 31315975 | 2019 | Structural characterization of an activin class ternary receptor complex reveals a third paradigm for receptor specificity. | 39 |
| 29203340 | 2018 | Decidual ACVR2A regulates extravillous trophoblast functions of adhesion, proliferation, migration and invasion in vitro. | 4 |
Citation
Jessica Bauer ; Sarah Boles ; Eddy Chau ; Barbara Jung
ACVR2A (Activin Receptor Type 2)
Atlas Genet Cytogenet Oncol Haematol. 2012-05-01
Online version: http://atlasgeneticsoncology.org/gene/567/acvr2a-(activin-receptor-type-2)
Historical Card
2007-06-01 ACVR2A (Activin Receptor Type 2) by Sarah Boles,Eddy Chau,Barbara Jung  Affiliation
GI fellowship program Division of Gastroenterology, University of California, San Diego 9500 Gilman Drive 0063 La Jolla, CA, 92093-0063, USA
