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ACVR2A (Activin Receptor Type 2)

Written2007-06Sarah 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
Updated2012-05Jessica 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, EC)

(Note : for Links provided by Atlas : click)

Identity

Other namesACVR2
ACTRII
ACTR-IIA
ACTRIIA
HGNC (Hugo) ACVR2A
LocusID (NCBI) 92
Atlas_Id 567
Location 2q22.3  [Link to chromosome band 2q22]
Location_base_pair Starts at 148602086 and ends at 148688396 bp from pter ( according to hg19-Feb_2009)  [Mapping ACVR2A.png]
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.
Fusion genes
(updated 2016)
ACVR2A (2q22.3) / AKT3 (1q43)ACVR2A (2q22.3) / CASP8 (2q33.1)FN1 (2q35) / ACVR2A (2q22.3)
IGF2R (6q25.3) / ACVR2A (2q22.3)MBD5 (2q23.1) / ACVR2A (2q22.3)

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.

Protein

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

Note
Entity 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.
  
Entity Microsatellite stable colon cancer
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.
  

Bibliography

Activation of signalling by the activin receptor complex.
Attisano L, Wrana JL, Montalvo E, Massague J.
Mol Cell Biol. 1996 Mar;16(3):1066-73.
PMID 8622651
 
Activin signaling and its role in regulation of cell proliferation, apoptosis, and carcinogenesis.
Chen YG, Wang Q, Lin SL, Chang CD, Chuang J, Ying SY.
Exp Biol Med (Maywood). 2006 May;231(5):534-44. (REVIEW)
PMID 16636301
 
Flanking nucleotide specificity for DNA mismatch repair-deficient frameshifts within activin receptor 2 (ACVR2).
Chung H, Chaudhry J, Lai JF, Young DJ, Carethers JM.
Mutat Res. 2012 Jan 3;729(1-2):73-80. doi: 10.1016/j.mrfmmm.2011.09.009. Epub 2011 Oct 5.
PMID 22001236
 
Genetic association of the activin A receptor gene (ACVR2A) and pre-eclampsia.
Fitzpatrick E, Johnson MP, Dyer TD, Forrest S, Elliott K, Blangero J, Brennecke SP, Moses EK.
Mol Hum Reprod. 2009 Mar;15(3):195-204. Epub 2009 Jan 6.
PMID 19126782
 
Expression of type II activin receptor genes during differentiation of human K562 cells and cDNA cloning of the human type IIB activin receptor.
Hilden K, Tuuri T, Eramaa M, Ritvos O.
Blood. 1994 Apr 15;83(8):2163-70.
PMID 8161782
 
Loss of activin receptor type 2 protein expression in microsatellite unstable colon cancers.
Jung B, Doctolero RT, Tajima A, Nguyen AK, Keku T, Sandler RS, Carethers JM.
Gastroenterology. 2004 Mar;126(3):654-9.
PMID 14988818
 
Activin signaling in microsatellite stable colon cancers is disrupted by a combination of genetic and epigenetic mechanisms.
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.
PLoS One. 2009 Dec 14;4(12):e8308.
PMID 20011542
 
Influence of target gene mutations on survival, stage and histology in sporadic microsatellite unstable colon cancers.
Jung B, Smith EJ, Doctolero RT, Gervaz P, Alonso JC, Miyai K, Keku T, Sandler RS, Carethers JM.
Int J Cancer. 2006 May 15;118(10):2509-13.
PMID 16380996
 
Activin type 2 receptor restoration in MSI-H colon cancer suppresses growth and enhances migration with activin.
Jung BH, Beck SE, Cabral J, Chau E, Cabrera BL, Fiorino A, Smith EJ, Bocanegra M, Carethers JM.
Gastroenterology. 2007 Feb;132(2):633-44. Epub 2006 Nov 16.
PMID 17258738
 
Characterization of isoforms of activin receptor-interacting protein 2 that augment activin signaling.
Liu ZH, Tsuchida K, Matsuzaki T, Bao YL, Kurisaki A, Sugino H.
J Endocrinol. 2006 May;189(2):409-21.
PMID 16648306
 
Characterization of type II activin receptors. Binding, processing, and phosphorylation.
Mathews LS, Vale WW.
J Biol Chem. 1993 Sep 5;268(25):19013-8.
PMID 8395525
 

Citation

This paper should be referenced as such :
Bauer, J ; Boles, S ; Chau, E ; Jung, B
ACVR2A (Activin Receptor Type 2)
Atlas Genet Cytogenet Oncol Haematol. 2012;16(10):714-715.
Free journal version : [ pdf ]   [ DOI ]
On line version : http://AtlasGeneticsOncology.org/Genes/ACVR2ID567ch2q22.html
History of this paper:
Boles, S ; Chau, E ; Jung, B. ACVR2 (activin receptor type 2). Atlas Genet Cytogenet Oncol Haematol. 2008;12(1):1-2.
http://documents.irevues.inist.fr/bitstream/handle/2042/38460/06-2007-ACVR2ID567ch2q22.pdf


Other Solid tumors implicated (Data extracted from papers in the Atlas) [ 0 ]
  Colon: Colorectal adenocarcinoma

External links

Nomenclature
HGNC (Hugo)ACVR2A   173
Cards
AtlasACVR2ID567ch2q22
Entrez_Gene (NCBI)ACVR2A  92  activin A receptor type 2A
AliasesACTRII; ACVR2
GeneCards (Weizmann)ACVR2A
Ensembl hg19 (Hinxton)ENSG00000121989 [Gene_View]  chr2:148602086-148688396 [Contig_View]  ACVR2A [Vega]
Ensembl hg38 (Hinxton)ENSG00000121989 [Gene_View]  chr2:148602086-148688396 [Contig_View]  ACVR2A [Vega]
ICGC DataPortalENSG00000121989
TCGA cBioPortalACVR2A
AceView (NCBI)ACVR2A
Genatlas (Paris)ACVR2A
WikiGenes92
SOURCE (Princeton)ACVR2A
Genomic and cartography
GoldenPath hg19 (UCSC)ACVR2A  -     chr2:148602086-148688396 +  2q22.2-q23.3   [Description]    (hg19-Feb_2009)
GoldenPath hg38 (UCSC)ACVR2A  -     2q22.2-q23.3   [Description]    (hg38-Dec_2013)
EnsemblACVR2A - 2q22.2-q23.3 [CytoView hg19]  ACVR2A - 2q22.2-q23.3 [CytoView hg38]
Mapping of homologs : NCBIACVR2A [Mapview hg19]  ACVR2A [Mapview hg38]
OMIM102581   
Gene and transcription
Genbank (Entrez)AA125825 AK301629 AK314124 AW162986 BC067416
RefSeq transcript (Entrez)NM_001278579 NM_001278580 NM_001616
RefSeq genomic (Entrez)NC_000002 NC_018913 NT_005403 NW_004929304
Consensus coding sequences : CCDS (NCBI)ACVR2A
Cluster EST : UnigeneHs.470174 [ NCBI ]
CGAP (NCI)Hs.470174
Alternative Splicing GalleryENSG00000121989
Gene ExpressionACVR2A [ NCBI-GEO ]   ACVR2A [ EBI - ARRAY_EXPRESS ]   ACVR2A [ SEEK ]   ACVR2A [ MEM ]
Gene Expression Viewer (FireBrowse)ACVR2A [ Firebrowse - Broad ]
SOURCE (Princeton)Expression in : [Datasets]   [Normal Tissue Atlas]  [carcinoma Classsification]  [NCI60]
GenevisibleExpression in : [tissues]  [cell-lines]  [cancer]  [perturbations]  
BioGPS (Tissue expression)92
GTEX Portal (Tissue expression)ACVR2A
Protein : pattern, domain, 3D structure
UniProt/SwissProtP27037 (Uniprot)
NextProtP27037  [Sequence]  [Exons]  [Medical]  [Publications]
With graphics : InterProP27037
Splice isoforms : SwissVarP27037 (Swissvar)
Catalytic activity : Enzyme2.7.11.30 [ Enzyme-Expasy ]   2.7.11.302.7.11.30 [ IntEnz-EBI ]   2.7.11.30 [ BRENDA ]   2.7.11.30 [ KEGG ]   
PhosPhoSitePlusP27037
Domaine pattern : Prosite (Expaxy)PROTEIN_KINASE_DOM (PS50011)    PROTEIN_KINASE_ST (PS00108)   
Domains : Interpro (EBI)Activin_recp    Kinase-like_dom    Prot_kinase_dom    Ser/Thr_kinase_AS    TGFB_receptor   
Domain families : Pfam (Sanger)Activin_recp (PF01064)    Pkinase (PF00069)   
Domain families : Pfam (NCBI)pfam01064    pfam00069   
DMDM Disease mutations92
Blocks (Seattle)ACVR2A
PDB (SRS)3Q4T    3SOC    4ASX   
PDB (PDBSum)3Q4T    3SOC    4ASX   
PDB (IMB)3Q4T    3SOC    4ASX   
PDB (RSDB)3Q4T    3SOC    4ASX   
Structural Biology KnowledgeBase3Q4T    3SOC    4ASX   
SCOP (Structural Classification of Proteins)3Q4T    3SOC    4ASX   
CATH (Classification of proteins structures)3Q4T    3SOC    4ASX   
SuperfamilyP27037
Human Protein AtlasENSG00000121989
Peptide AtlasP27037
HPRD00025
IPIIPI00015691   IPI01011494   
Protein Interaction databases
DIP (DOE-UCLA)P27037
IntAct (EBI)P27037
FunCoupENSG00000121989
BioGRIDACVR2A
STRING (EMBL)ACVR2A
ZODIACACVR2A
Ontologies - Pathways
QuickGOP27037
Ontology : AmiGOgastrulation with mouth forming second  positive regulation of protein phosphorylation  protein serine/threonine kinase activity  transmembrane receptor protein serine/threonine kinase activity  receptor signaling protein serine/threonine kinase activity  protein binding  protein binding  ATP binding  cytoplasm  plasma membrane  integral component of plasma membrane  transmembrane receptor protein serine/threonine kinase signaling pathway  spermatogenesis  determination of left/right symmetry  mesoderm development  anterior/posterior pattern specification  cell surface  positive regulation of pathway-restricted SMAD protein phosphorylation  coreceptor activity  activin-activated receptor activity  growth factor binding  signal transduction by protein phosphorylation  PDZ domain binding  positive regulation of bone mineralization  BMP signaling pathway  BMP signaling pathway  BMP signaling pathway  regulation of BMP signaling pathway  activin receptor signaling pathway  positive regulation of activin receptor signaling pathway  inhibin-betaglycan-ActRII complex  inhibin binding  sperm ejaculation  penile erection  receptor complex  protein self-association  positive regulation of erythrocyte differentiation  positive regulation of osteoblast differentiation  positive regulation of transcription from RNA polymerase II promoter  metal ion binding  activin binding  embryonic skeletal system development  regulation of nitric-oxide synthase activity  Sertoli cell proliferation  cellular response to BMP stimulus  BMP receptor activity  
Ontology : EGO-EBIgastrulation with mouth forming second  positive regulation of protein phosphorylation  protein serine/threonine kinase activity  transmembrane receptor protein serine/threonine kinase activity  receptor signaling protein serine/threonine kinase activity  protein binding  protein binding  ATP binding  cytoplasm  plasma membrane  integral component of plasma membrane  transmembrane receptor protein serine/threonine kinase signaling pathway  spermatogenesis  determination of left/right symmetry  mesoderm development  anterior/posterior pattern specification  cell surface  positive regulation of pathway-restricted SMAD protein phosphorylation  coreceptor activity  activin-activated receptor activity  growth factor binding  signal transduction by protein phosphorylation  PDZ domain binding  positive regulation of bone mineralization  BMP signaling pathway  BMP signaling pathway  BMP signaling pathway  regulation of BMP signaling pathway  activin receptor signaling pathway  positive regulation of activin receptor signaling pathway  inhibin-betaglycan-ActRII complex  inhibin binding  sperm ejaculation  penile erection  receptor complex  protein self-association  positive regulation of erythrocyte differentiation  positive regulation of osteoblast differentiation  positive regulation of transcription from RNA polymerase II promoter  metal ion binding  activin binding  embryonic skeletal system development  regulation of nitric-oxide synthase activity  Sertoli cell proliferation  cellular response to BMP stimulus  BMP receptor activity  
Pathways : KEGGCytokine-cytokine receptor interaction    TGF-beta signaling pathway   
REACTOMEP27037 [protein]
REACTOME PathwaysR-HSA-1502540 Signaling by Activin [pathway]
REACTOME PathwaysR-HSA-1433617 Regulation of signaling by NODAL [pathway]
REACTOME PathwaysR-HSA-201451 Signaling by BMP [pathway]
REACTOME PathwaysR-HSA-1181150 Signaling by NODAL [pathway]
NDEx NetworkACVR2A
Atlas of Cancer Signalling NetworkACVR2A
Wikipedia pathwaysACVR2A
Orthology - Evolution
OrthoDB92
GeneTree (enSembl)ENSG00000121989
Phylogenetic Trees/Animal Genes : TreeFamACVR2A
Homologs : HomoloGeneACVR2A
Homology/Alignments : Family Browser (UCSC)ACVR2A
Gene fusions - Rearrangements
Fusion : MitelmanACVR2A/AKT3 [2q22.3/1q43]  
Fusion : MitelmanACVR2A/CASP8 [2q22.3/2q33.1]  [t(2;2)(q22;q33)]  
Fusion : MitelmanIGF2R/ACVR2A [6q25.3/2q22.3]  [t(2;6)(q22;q25)]  
Fusion : MitelmanMBD5/ACVR2A [2q23.1/2q22.3]  [t(2;2)(q22;q23)]  
Fusion: TCGAACVR2A 2q22.3 AKT3 1q43 PRAD
Fusion: TCGAACVR2A 2q22.3 CASP8 2q33.1 LUSC
Fusion: TCGAIGF2R 6q25.3 ACVR2A 2q22.3 BRCA
Fusion: TCGAMBD5 2q23.1 ACVR2A 2q22.3 HNSC
Polymorphisms : SNP, variants
NCBI Variation ViewerACVR2A [hg38]
dbSNP Single Nucleotide Polymorphism (NCBI)ACVR2A
dbVarACVR2A
ClinVarACVR2A
1000_GenomesACVR2A 
Exome Variant ServerACVR2A
ExAC (Exome Aggregation Consortium)ACVR2A (select the gene name)
Genetic variants : HAPMAP92
Genomic Variants (DGV)ACVR2A [DGVbeta]
Mutations
ICGC Data PortalACVR2A 
TCGA Data PortalACVR2A 
Broad Tumor PortalACVR2A
OASIS PortalACVR2A [ Somatic mutations - Copy number]
Somatic Mutations in Cancer : COSMICACVR2A 
intOGen PortalACVR2A
LOVD (Leiden Open Variation Database)Whole genome datasets
LOVD (Leiden Open Variation Database)LOVD 3.0 shared installation
BioMutasearch ACVR2A
DgiDB (Drug Gene Interaction Database)ACVR2A
DoCM (Curated mutations)ACVR2A (select the gene name)
CIViC (Clinical Interpretations of Variants in Cancer)ACVR2A (select a term)
intoGenACVR2A
Impact of mutations[PolyPhen2] [SIFT Human Coding SNP] [Buck Institute : MutDB] [Mutation Assessor] 
Diseases
DECIPHER (Syndromes)2:148602086-148688396  ENSG00000121989
CONAN: Copy Number AnalysisACVR2A 
Mutations and Diseases : HGMDACVR2A
OMIM102581   
MedgenACVR2A
Genetic Testing Registry ACVR2A
NextProtP27037 [Medical]
TSGene92
GENETestsACVR2A
Huge Navigator ACVR2A [HugePedia]
snp3D : Map Gene to Disease92
BioCentury BCIQACVR2A
ClinGenACVR2A
Clinical trials, drugs, therapy
Chemical/Protein Interactions : CTD92
Chemical/Pharm GKB GenePA24494
Clinical trialACVR2A
Miscellaneous
canSAR (ICR)ACVR2A (select the gene name)
Probes
Litterature
PubMed101 Pubmed reference(s) in Entrez
GeneRIFsGene References Into Functions (Entrez)
CoreMineACVR2A
EVEXACVR2A
GoPubMedACVR2A
iHOPACVR2A
REVIEW articlesautomatic search in PubMed
Last year publicationsautomatic search in PubMed

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indexed on : Mon Sep 19 19:36:42 CEST 2016

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