ACVR2A (Activin Receptor Type 2)

2012-05-01   Jessica Bauer , Sarah Boles , Eddy Chau , Barbara Jung 

Identity

HGNC
LOCATION
2q22.3
LOCUSID
ALIAS
ACTRII,ACVR2
FUSION GENES

DNA/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.

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.

Bibliography

Pubmed IDLast YearTitleAuthors
86226511996Activation of signalling by the activin receptor complex.Attisano L et al
166363012006Activin signaling and its role in regulation of cell proliferation, apoptosis, and carcinogenesis.Chen YG et al
220012362012Flanking nucleotide specificity for DNA mismatch repair-deficient frameshifts within activin receptor 2 (ACVR2).Chung H et al
191267822009Genetic association of the activin A receptor gene (ACVR2A) and pre-eclampsia.Fitzpatrick E et al
81617821994Expression 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
149888182004Loss of activin receptor type 2 protein expression in microsatellite unstable colon cancers.Jung B et al
200115422009Activin signaling in microsatellite stable colon cancers is disrupted by a combination of genetic and epigenetic mechanisms.Jung B et al
163809962006Influence of target gene mutations on survival, stage and histology in sporadic microsatellite unstable colon cancers.Jung B et al
172587382007Activin type 2 receptor restoration in MSI-H colon cancer suppresses growth and enhances migration with activin.Jung BH et al
166483062006Characterization of isoforms of activin receptor-interacting protein 2 that augment activin signaling.Liu ZH et al
83955251993Characterization 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 IDTranscript IDUniprot
ENSG00000121989ENST00000241416P27037
ENSG00000121989ENST00000404590P27037
ENSG00000121989ENST00000535787P27037

Expression (GTEx)

0
5
10
15
20
25
30

Pathways

PathwaySourceExternal ID
Cytokine-cytokine receptor interactionKEGGko04060
TGF-beta signaling pathwayKEGGko04350
Cytokine-cytokine receptor interactionKEGGhsa04060
TGF-beta signaling pathwayKEGGhsa04350
Signaling pathways regulating pluripotency of stem cellsKEGGhsa04550
Signaling pathways regulating pluripotency of stem cellsKEGGko04550
BMP signalingKEGGhsa_M00679
Activin signalingKEGGhsa_M00681
BMP signalingKEGGM00679
Activin signalingKEGGM00681
Signal TransductionREACTOMER-HSA-162582
Signaling by BMPREACTOMER-HSA-201451
Signaling by ActivinREACTOMER-HSA-1502540
Developmental BiologyREACTOMER-HSA-1266738
Signaling by NODALREACTOMER-HSA-1181150
Regulation of signaling by NODALREACTOMER-HSA-1433617
Fluid shear stress and atherosclerosisKEGGko05418
Fluid shear stress and atherosclerosisKEGGhsa05418

Protein levels (Protein atlas)

Not detected
Low
Medium
High

References

Pubmed IDYearTitleCitations
232634862013Genome-wide association analyses identify 18 new loci associated with serum urate concentrations.242
166723632006Structure of the ternary signaling complex of a TGF-beta superfamily member.84
126674452003The BMP7/ActRII extracellular domain complex provides new insights into the cooperative nature of receptor assembly.72
203796142010Personalized smoking cessation: interactions between nicotine dose, dependence and quit-success genotype score.62
195030632009Tumor-infiltrating lymphocytes in colorectal cancers with microsatellite instability are correlated with the number and spectrum of frameshift mutations.55
149888182004Loss of activin receptor type 2 protein expression in microsatellite unstable colon cancers.50
174729602007Repulsive guidance molecule RGMa alters utilization of bone morphogenetic protein (BMP) type II receptors by BMP2 and BMP4.44
202003322010Family-based analysis of candidate genes for polycystic ovary syndrome.40
207340642010A large-scale candidate gene association study of age at menarche and age at natural menopause.38
260479462015Activin A inhibits BMP-signaling by binding ACVR2A and ACVR2B.35

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 

GI fellowship program Division of Gastroenterology, University of California, San Diego 9500 Gilman Drive 0063 La Jolla, CA, 92093-0063, USA