Atlas of Genetics and Cytogenetics in Oncology and Haematology


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TGFBR3 (transforming growth factor, beta receptor III)

Identity

Other namesBGCAN
Betaglycan
TbetaRIII
TGFR-3
HGNC (Hugo) TGFBR3
LocusID (NCBI) 7049
Location 1p22.1
Location_base_pair Starts at 92145900 and ends at 92351836 bp from pter ( according to hg19-Feb_2009)  [Mapping]

DNA/RNA

Description The TGFbetaR3 gene encodes 16 exons.
Transcription The human TGFBR3 gene has two promoters, a proximal promoter and a distal promoter and produces a 4,2 kb mRNA. TGF-beta1 has been demonstrated to down regulate TbetaRIII expression through direct inhibition of the proximal TbetaRIII promoter.

Protein

 
  Structure of TbetaRIII. TbetaRIII consists of a large extracellular domain, which has multiple sites of glycan modification, including N- and O-glycans, and glycosaminoglycan side chains, a hydrophobic transmembrane domain, and a short cytoplasmic domain. TbetaRIII interacts with the scaffolding proteins beta-arrestin2, via phosphorylation of amino acid site Thr841 in the cytoplasmic domain, and with GIPC via the PDZ domain.
Description TbetaRIII is an 853 amino acid transmembrane proteoglycan, which contains a short 41 amino acid cytoplasmic domain. TbetaRIII is a proteoglycan, with glycosaminoglycan (GAG) side chain modifications (S535 and S546) composed of heparin and chondroitin sulfate. The TbetaRIII core has predicted molecular weight of 100 kDa, however fully processed TbetaRIII migrates at an apparent molecular weight of 180 to 300 kDa due to these glycosaminoglycan post-translational modifications. TbetaRIII contains a class I PDZ binding motif and a beta-arrestin2 interacting motif in the cytoplasmic domain, as well as a ZP-1 (zona pellucida) domain in the extracellular domain. The cytoplasmic domain of TbetaRIII is phosphorylated by TbetaRII. TbetaRIII also undergoes ectodomain shedding to produce soluble TbetaRIII (sTbetaRIII).
Expression TbetaRIII is ubiquitously expressed on nearly all cell types. Some cell types, including endothelial and hematopoietic cells, appear to have low to no TbetaRIII expression. The level of TbetaRIII expression is cell type specific.
Localisation TbetaRIII exists as a transmembrane protein in the cell membrane and as a secreted protein, known as soluble TbetaRIII (sTbetaRIII), which can be detected in the extracellular matrix and serum.
Function TbetaRIII is a member of the TGF-beta superfamily signaling pathways, which have essential roles in mediating cell proliferation, apoptosis, differentiation, and migration in most human tissues. TbetaRIII is the most abundantly expressed TGF-beta superfamily receptor and functions as a TGF-beta superfamily co-receptor, by binding the TGF-beta superfamily members, TGF-beta1, TGF-beta2, or TGF-beta3, inhibin, BMP-2, BMP-4, BMP-7, and GDF-5 and presents these ligand to their respective signaling receptors to activate or repress (in the case of inhibin) TGF-beta1, BMP, or activin signaling to the Smad transcription factors. For example, in the case of TGF-beta1, 2, or 3, TbetaRIII presents ligand to the TGF-beta type II receptor (TbetaRII). Once bound to ligand, TbetaRII then recruits and transphosphorylates the TGF-beta type I receptor (TbetaRI), activating its kinase function and leading to the phosphorylation of Smad2/3. Phosphorylation of Smad2 and Smad3 leads to formation of a complex with Smad4, and accumulation of this complex in the nucleus, where along with co-activators and co-repressors they regulate the transcription of genes involved in proliferation, angiogenesis, apoptosis, and differentiation. In addition to regulating receptor mediated Smad signaling, TbetaRIII also mediates ligand dependent and independent p38 pathway signaling. TbetaRIII can also undergo ectodomain shedding to generate soluble TbetaRIII (sTbetaRIII), which binds and sequesters TGF-beta superfamily members to inhibit their signaling. Although sTbetaRIII expression has been demonstrated to correlate with the cell surface expression of TbetaRIII, little is known about the regulation of sTbetaRIII production. TbetaRIII shedding may be mediated in part by the membrane type matrix metalloproteases (MT-MMP) MT1-MMP and/or MT3-MMP, and plasmin, a serine proteinase which has been shown to cleave the extracellular domain of TbetaRIII. In addition, TbetaRIII shedding is modulated by pervanadate, a tyrosine phosphatase inhibitor. Supporting this, TAPI-2, a MT-MMP and ADAM protease inhibitor, has been shown to inhibit TbetaRIII shedding. The regulation of TbetaRIII expression is sufficient to alter TGF-beta signaling. The cytoplasmic domain of TbetaRIII interacts with GIPC, a PDZ-domain containing protein, which stabilizes TbetaRIII cell surface expression and increases TGF-beta signaling. The interaction between TbetaRIII and GIPC also plays an important role in TbetaRIII mediated inhibition of TGF-beta signaling, cell migration, and invasion during breast cancer progression. The cytoplasmic domain of TbetaRIII is phosphorylated by TbetaRII, which results in TbetaRIII binding to the scaffolding protein beta-arrestin2. The TbetaRIII/beta-arrestin2 interaction results in the co-internalization of beta-arrestin2/TbetaRIII/ TbetaRII and the down-regulation of TGF-beta signaling. The interaction between TbetaRIII and beta-arrestin2 regulates BMP signaling as well as TGF-beta signaling. TbetaRIII complexes with ALK6, a BMP type I receptor, in a beta-arrestin2 dependent manner to mediate the internalization of ALK6 and stimulation of ALK6 specific BMP signaling events. Through its interaction with beta-arrestin2, TbetaRIII negatively regulates NFκ-B signaling in the context of breast cancer, regulates epithelial cellular adhesion to fibronectin, fibrillogenesis, and focal adhesion formation via regulation of alpha5beta1 internalization and trafficking to nascent focal adhesions, activates Cdc42, to alter the actin cytoskeleton and suppresses migration in normal and cancerous ovarian epithelial cells. During development, TbetaRIII has an important role in the formation of the atrioventricular cushion in the heart. Consistent with an important role for TbetaRIII during development, TGFbetaR3 null mice are embryonic lethal due to heart and liver defects. TGFbetaR3 has been recently identified as a tumor suppressor in multiple types of human cancers, including breast, lung, ovarian, pancreatic and prostate cancer. The loss of TGFbetaR3 in these cancer types correlates with disease progression, and results in increased motility and invasion in vitro and increased invasion and metastasis in vivo.
Homology TbetaRIII shares several regions of homology with the superfamily co-receptor, endoglin, with 2 regions of homology in the extracellular domain, a large domain near the amino terminus with 21% homology, and a shorter domain near the sites of GAG modification with 50% homology. In addition, their cytoplasmic domains share 70% homology.

Mutations

Somatic There is a high rate of rearrangements at the TGFBR3 locus in myxoinflammatory fibroblastic sarcomas (MIFS) and hemosiderotic fibrolipomatous tumors (HFLT). Mutations in TbetaRIII have not been found in other human cancers.

Implicated in

Entity Breast cancer
Disease Breast cancer is the second leading cause of cancer death in women, exceeded only by lung cancer in the United States. Types of breast cancer include ductal carcinoma in situ (DCIS), lobular carcinoma in situ (LCIS), and invasive or infiltrating ductal carcinoma (IDC).
Prognosis The current five year survival rate for breast cancer is 98% for localized cancer, 80% for regional cancer, and 27% for metastatic disease with distant spread.
Oncogenesis TbetaRIII loss occurs relatively early in mammary carcinogenesis, with loss beginning in the pre-invasive state of DCIS. The degree of TbetaRIII loss correlates with breast cancer progression and with a decrease in patient survival. TbetaRIII loss in breast cancer is due to LOH (loss of heterozygosity) at the TGFbetaR3 gene locus and potential transcriptional down regulation of TbetaRIII by increased levels of TGF-beta in the tumor microenvironment. Restoring TbetaRIII expression inhibits tumor invasion, angiogenesis, and metastasis in vivo. TbetaRIII functions, in part, through the production of sTbetaRIII by ectodomain shedding, which antagonizes TGF-beta signaling, leading to a decrease in invasiveness and angiogenesis in vivo. In addition, the TbetaRIII cytoplasmic domain, specifically the interaction with GIPC, is required for TbetaRIII mediated inhibition of breast cancer progression. TbetaRIII also functions as a tumor suppressor in non-tumorigenic mammary epithelial cells through the inhibition of NFkappa-B mediation repression of E-cadherin. Loss of TbetaRIII in non-tumorigenic mammary epithelial cells leads to increased invasive capabilities due to up-regulated NFkappa-B activity and loss of E-cadherin expression.
  
Entity Colorectal cancer
Disease Colon cancer is the third most commonly diagnosed cancer in in men and women in the United States and is the third leading cause of death in men and women.
Prognosis The five year survival rate for colon cancer by stage is: stage 1: 93%, stage II: 78%, stage III: 64%, and stage IV: 8%.
Oncogenesis Evidence suggests that TbetaRIII may promote colon cancer progression. In contrast to other cancer types, TbetaRIII expression is unaltered at the mRNA level and increases at the protein level in human colon cancer. Increasing TbetaRIII expression in colon cancer cells enhances ligand mediated phosphorylation of p38 and the Smad proteins and increase cell proliferation in response to ligand stimulation, inhibiting ligand mediated induction of p21 and p27. In addition, increasing TbetaRIII expression enhances cell migration, anchorage-independent growth, resistance to ligand and chemotherapeutic induced apoptosis and modestly enhances tumorigenicity in a xenograft model of colon cancer. Reciprocally, silencing endogenous TbetaRIII inhibited ligand induced migration. These data support a role for TbetaRIII as a mediator of colon cancer progression.
  
Entity Hepatocellular carcinoma
Disease Hepatocellular carcinoma (HCC) is the most common type of primary liver cancer, the 5th most common cancer worldwide and the 3rd leading cause of cancer deaths worldwide. The vast majority of cases arise in the setting of pre-existing liver disease, which can result from viral hepatitis, alcohol use, or toxin exposure.
Prognosis 5-year survival rates are quite poor (<12%), due in part to the often-advanced stage of disease at diagnosis, and the ineffectiveness of standard chemotherapeutic treatments.
Oncogenesis TbetaRIII may function as a tumor suppressor in HCC. TGFBR3 expression is decreased in the progression from normal tissue to precancerous lesion to invasive carcinoma, based on DNA microarray data and qRT-PCR analysis. This decreased expression does not appear to be a result of mutations in the TGFBR3 gene, and HCC samples also showed a low rate of loss of heterozygosity for TGFBR3, indicating that other mechanisms are likely responsible for its down-regulation.
  
Entity Multiple myeloma
Disease Multiple myeloma (MM) is the second most common hematologic malignancy. Most frequently arising in older individuals, it accounts for 10-15% of hematologic malignancies and 1-2% of all human cancers.
Prognosis MM is generally regarded as incurable, with a poor 5-year survival rate of 31%.
Oncogenesis TbetaRIII likely acts as a tumor suppressor in multiple myeloma. TbetaRIII mRNA expression is down-regulated during MM progression, decreasing from normal bone marrow to MGUS to MM, and TbetaRIII also has decreased expression at the protein level in human MM specimens compared to normal bone marrow controls. Restoration of TbetaRIII expression in vitro decreases cell growth and proliferation rates in myeloma cells and is associated with significantly increased levels of the cyclin-dependent kinase inhibitors p21 and p27. Expression of TbetaRIII also decreases adhesion to bone marrow stromal cells and increases homotypic adhesion among myeloma cells. Lastly, restoration of TbetaRIII expression in myeloma cells significantly inhibits cell motility in a ligand-independent manner.
  
Entity Myxoinflammatory fibroblastic sarcoma (MIFS) and hemosiderotic fibrolipomatous tumor (HFLT)
Disease Myxoinflammatory fibroblastic sarcoma (MIFS) and hemosiderotic fibrolipomatous tumor (HFLT) are rare types of low-grade sarcoma that typically present as painless, slow-growing masses in the soft tissue of distal extremities.
Prognosis Prognosis is very good for both tumor types. MIFS has a local recurrence rate of 22-67%, but distant metastasis is very rare, observed in less than 2% of all reported cases. A case series of HFLT showed a local recurrence rate of 33%, but no occurrences of metastasis.
Oncogenesis MIFS and HFLT share a high incidence of t(1;10)(p22;q24) translocations, with the breakpoint at 1p22 mapped to the TGFBR3 locus. Cytogenetic analysis has shown a high rate of rearrangements at the TGFBR3 locus in both tumor types, possibly indicating a shared mechanism of pathogenesis that involves TbetaRIII for these two rare sarcomas.
  
Entity Oral squamous cell carcinoma (OSCC)
Disease Oral squamous cell carcinoma (OSCC) is the most common type of malignant oral lesion (>90%). It is thought to arise in a stepwise process, from normal epithelium to premalignant lesions such oral leukoplakia, to carcinoma in situ, and finally to invasive carcinoma.
Prognosis Five-year survival for OSCC is roughly 50%, with females having a significantly higher survival rate than males.
Oncogenesis TbetaRIII expression is significantly down-regulated at the protein level in OSCC compared to normal epithelium - roughly 50% of cancer specimens show low or absent TbetaRIII expression. Decreased expression correlates with disease progression, and TbetaRIII loss appears to be an early event in carcinogenesis. TbetaRIII is also significantly decreased in cancer-associated fibroblasts compared to normal fibroblasts.
  
Entity Non-small cell lung cancer (NSCLC)
Disease Lung cancer is the leading cause of death of both males and females in the United States. Non-small cell lung cancer accounts for 87% of all lung cancers.
Prognosis The five year survival rate for all stages of lung cancer is 15%. The survival rate is 49% for localized disease; however few cases are identified at this stage.
Oncogenesis TbetaRIII has been characterized as a tumor suppressor in non-small cell lung cancer. Expression of TbetaRIII is lost in the majority of non-small cell lung cancer (NSCLC) at both the mRNA expression level and the protein level. Loss of heterozygosity (LOH) occurs in 38,5% of NSCLC human specimens and correlates with decreased TbetaRIII expression, suggesting that LOH is one mechanism of loss of TbetaRIII expression. Loss of TbetaRIII expression correlates with NSCLC progression and increasing tumor grade, with a trend towards decreased survival. The loss of TbetaRIII results in a functional increase in cellular migration, invasion, and anchorage independent growth of lung cancer cells. TbetaRIII regulates cellular invasion and motility in lung cancer in part through the generation of sTbetaRIII, although the mechanism of these effects remains unclear.
  
Entity Prostate cancer
Disease Prostate cancer is the most commonly diagnosed malignancy in men and the third leading cause of cancer-related deaths among men in the United States.
Prognosis The five year survival rate for all stages of prostate cancer is near 99%. The five year survival rate for local and regional disease approaches 100%.
Oncogenesis TbetaRIII has been characterized as a tumor suppressor in prostate cancer. Expression of TbetaRIII is lost or decreased in the majority of human prostate cancers at both the mRNA and protein level, due to the loss of heterozygosity at the TbetaRIII locus and epigenetic regulation of the TbetaRIII promoter. Loss of TbetaRIII correlates with advancing tumor stage and an increased probability of prostate-specific antigen (PSA) recurrence. Restoring TbetaRIII expression in prostate cancer cells decreases cell motility and cell invasion in vitro and tumorigenicity in vivo. The loss of TbetaRIII is a common event in human prostate cancer cells and is important for tumor progression through effects on cell motility, invasiveness, and tumorigenicity.
  
Entity Ovarian cancer
Disease Ovarian cancer is the fifth leading cause of cancer death among women in the United States. The majority of ovarian cancers are ovarian epithelial carcinomas or malignant germ cell tumors.
Prognosis The overall five year survival rate is 45% for ovarian cancer. The five year survival rate is 70% for patients with regional disease. However the lack of effective treatments for metastatic disease and the aggressive nature of this disease results in a 30% survival rate for those with metastatic disease.
Oncogenesis TbetaRIII has been characterized as a tumor suppressor in ovarian cancer. TbetaRIII expression is decreased or lost in epithelial derived ovarian cancer at both the mRNA and protein level due to epigenetic silencing which is progressive with increasing tumor grade. TbetaRIII inhibits ovarian cancer cell invasiveness and migration. TbetaRIII specifically promotes the anti-migratory action of inhibin and inhibin-mediated repression of matrix metalloproteinases, which play a role in the invasive and metastatic potential of tumor cells.
  
Entity Pancreatic cancer
Disease Pancreatic cancer is the fourth leading cause of cancer death in the Unites States, with incidence levels closely matching the death rate. The majority of pancreatic cancers are adenocarcinomas, while endocrine pancreatic cancer is rare.
Prognosis Pancreatic cancer has a low survival rate, with the median survival rate being four to six months and a five year survival rate of less than 5%. The 5 year survival rate for local disease is 20%. This low survival rate is due to delayed diagnosis caused by a lack of symptoms until the cancer is locally invasive or metastatic, a lack of effective screening tests, and ineffective treatments.
Oncogenesis TbetaRIII may function as a tumor suppressor in pancreatic cancer. The genomic locus for TGFBR3 is deleted in 49% of human pancreatic cancers. Loss of TbetaRIII expression at the message and protein level correlates with worsening tumor grade in human pancreatic cancer specimens. In a pancreatic model of epithelial to mesenchymal transition (EMT), TbetaRIII expression is lost at the mRNA and protein levels. The loss of TbetaRIII protein expression occurs before the loss of E-cadherin and cytoskeletal reorganization, both markers of early EMT, and correlates with increased invasion and motility, hallmarks of EMT. The ability of TbetaRIII to suppress invasion and motility is partially mediated by sTbetaRIII.
  
Entity Renal cell carcinoma (RCC)
Disease RCC is the most common form of kidney cancer. There are several subtype of RCC including clear cell RCC, papillary RCC, chromophobe RCC, and collecting duct RCC.
Prognosis The 5 year survival rate for all stages of renal cell carcinoma is 65,5%. There is a lack of effective treatments for metastatic RCC and the 5 year survival rate is 9,5% for metastatic disease.
Oncogenesis Loss of TbetaRIII at both the mRNA and the protein level occurs in all RCC tumor stages. Loss of TbetaRIII RNA expression is an early event in RCC and leads to a partial loss of TGF-beta responsiveness and attenuation of TGF-beta signaling. The sequential loss of TbetaRII after TbetaRIII loss leads to complete TGF-beta resistance and a more aggressive, metastatic RCC phenotype. Restoring TbetaRIII expression in the presence of TbetaRII, leads to enhanced TGF-beta signaling, restoration of growth inhibition, and the loss of anchorage independent growth over that observed with TbetaRII alone.
  

Other Solid tumors implicated (Data extracted from papers in the Atlas)

Solid Tumors AmeloblastomID5945

External links

Nomenclature
HGNC (Hugo)TGFBR3   11774
Cards
AtlasTGFBR3ID42541ch1p33
Entrez_Gene (NCBI)TGFBR3  7049  transforming growth factor, beta receptor III
GeneCards (Weizmann)TGFBR3
Ensembl (Hinxton)ENSG00000069702 [Gene_View]  chr1:92145900-92351836 [Contig_View]  TGFBR3 [Vega]
ICGC DataPortalENSG00000069702
AceView (NCBI)TGFBR3
Genatlas (Paris)TGFBR3
WikiGenes7049
SOURCE (Princeton)NM_001195683 NM_001195684 NM_003243
Genomic and cartography
GoldenPath (UCSC)TGFBR3  -  1p22.1   chr1:92145900-92351836 -  1p33-p32   [Description]    (hg19-Feb_2009)
EnsemblTGFBR3 - 1p33-p32 [CytoView]
Mapping of homologs : NCBITGFBR3 [Mapview]
OMIM600742   
Gene and transcription
Genbank (Entrez)AI090023 AJ251961 AK225799 AK291345 BC099914
RefSeq transcript (Entrez)NM_001195683 NM_001195684 NM_003243
RefSeq genomic (Entrez)AC_000133 NC_000001 NC_018912 NG_027757 NT_032977 NW_001838589 NW_004929290
Consensus coding sequences : CCDS (NCBI)TGFBR3
Cluster EST : UnigeneHs.735919 [ NCBI ]
CGAP (NCI)Hs.735919
Alternative Splicing : Fast-db (Paris)GSHG0002258
Alternative Splicing GalleryENSG00000069702
Gene ExpressionTGFBR3 [ NCBI-GEO ]     TGFBR3 [ SEEK ]   TGFBR3 [ MEM ]
Protein : pattern, domain, 3D structure
UniProt/SwissProtQ03167 (Uniprot)
NextProtQ03167  [Medical]
With graphics : InterProQ03167
Splice isoforms : SwissVarQ03167 (Swissvar)
Domaine pattern : Prosite (Expaxy)ZP_1 (PS00682)    ZP_2 (PS51034)   
Domains : Interpro (EBI)ZP_dom    ZP_dom_CS   
Related proteins : CluSTrQ03167
Domain families : Pfam (Sanger)Zona_pellucida (PF00100)   
Domain families : Pfam (NCBI)pfam00100   
Domain families : Smart (EMBL)ZP (SM00241)  
DMDM Disease mutations7049
Blocks (Seattle)Q03167
Human Protein AtlasENSG00000069702
Peptide AtlasQ03167
HPRD02846
IPIIPI00304865   IPI00971143   IPI00983408   IPI00984114   IPI00973779   
Protein Interaction databases
DIP (DOE-UCLA)Q03167
IntAct (EBI)Q03167
FunCoupENSG00000069702
BioGRIDTGFBR3
IntegromeDBTGFBR3
STRING (EMBL)TGFBR3
Ontologies - Pathways
QuickGOQ03167
Ontology : AmiGOblood vessel development  response to hypoxia  blastocyst development  epithelial to mesenchymal transition  liver development  heart morphogenesis  transforming growth factor beta-activated receptor activity  type II transforming growth factor beta receptor binding  transforming growth factor beta receptor binding  protein binding  protein binding  glycosaminoglycan binding  glycosaminoglycan binding  proteinaceous extracellular matrix  extracellular space  extracellular space  endoplasmic reticulum  integral component of plasma membrane  immune response  transforming growth factor beta receptor signaling pathway  transforming growth factor beta receptor signaling pathway  transforming growth factor beta receptor complex assembly  heparin binding  external side of plasma membrane  cell surface  negative regulation of epithelial cell migration  negative regulation of epithelial to mesenchymal transition  coreceptor activity  cell growth  cell migration  fibroblast growth factor binding  PDZ domain binding  BMP signaling pathway  positive regulation of transforming growth factor beta receptor signaling pathway  negative regulation of transforming growth factor beta receptor signaling pathway  organ regeneration  response to follicle-stimulating hormone  inhibin-betaglycan-ActRII complex  response to prostaglandin E  response to luteinizing hormone  intracellular signal transduction  regulation of protein binding  SMAD binding  activin binding  transforming growth factor beta binding  negative regulation of epithelial cell proliferation  positive regulation of NF-kappaB transcription factor activity  negative regulation of cellular component movement  ventricular cardiac muscle tissue morphogenesis  palate development  cardiac muscle cell proliferation  definitive hemopoiesis  cardiac epithelial to mesenchymal transition  definitive erythrocyte differentiation  heart trabecula formation  pathway-restricted SMAD protein phosphorylation  extracellular vesicular exosome  transforming growth factor beta receptor activity, type III  
Ontology : EGO-EBIblood vessel development  response to hypoxia  blastocyst development  epithelial to mesenchymal transition  liver development  heart morphogenesis  transforming growth factor beta-activated receptor activity  type II transforming growth factor beta receptor binding  transforming growth factor beta receptor binding  protein binding  protein binding  glycosaminoglycan binding  glycosaminoglycan binding  proteinaceous extracellular matrix  extracellular space  extracellular space  endoplasmic reticulum  integral component of plasma membrane  immune response  transforming growth factor beta receptor signaling pathway  transforming growth factor beta receptor signaling pathway  transforming growth factor beta receptor complex assembly  heparin binding  external side of plasma membrane  cell surface  negative regulation of epithelial cell migration  negative regulation of epithelial to mesenchymal transition  coreceptor activity  cell growth  cell migration  fibroblast growth factor binding  PDZ domain binding  BMP signaling pathway  positive regulation of transforming growth factor beta receptor signaling pathway  negative regulation of transforming growth factor beta receptor signaling pathway  organ regeneration  response to follicle-stimulating hormone  inhibin-betaglycan-ActRII complex  response to prostaglandin E  response to luteinizing hormone  intracellular signal transduction  regulation of protein binding  SMAD binding  activin binding  transforming growth factor beta binding  negative regulation of epithelial cell proliferation  positive regulation of NF-kappaB transcription factor activity  negative regulation of cellular component movement  ventricular cardiac muscle tissue morphogenesis  palate development  cardiac muscle cell proliferation  definitive hemopoiesis  cardiac epithelial to mesenchymal transition  definitive erythrocyte differentiation  heart trabecula formation  pathway-restricted SMAD protein phosphorylation  extracellular vesicular exosome  transforming growth factor beta receptor activity, type III  
Pathways : BIOCARTACTCF: First Multivalent Nuclear Factor [Genes]    ALK in cardiac myocytes [Genes]    Role of Tob in T-cell activation [Genes]   
Protein Interaction DatabaseTGFBR3
Wikipedia pathwaysTGFBR3
Gene fusion - rearrangments
Polymorphisms : SNP, mutations, diseases
SNP Single Nucleotide Polymorphism (NCBI)TGFBR3
SNP (GeneSNP Utah)TGFBR3
SNP : HGBaseTGFBR3
Genetic variants : HAPMAPTGFBR3
1000_GenomesTGFBR3 
ICGC programENSG00000069702 
CONAN: Copy Number AnalysisTGFBR3 
Somatic Mutations in Cancer : COSMICTGFBR3 
LOVD (Leiden Open Variation Database)Whole genome datasets
LOVD (Leiden Open Variation Database)LOVD - Leiden Open Variation Database
LOVD (Leiden Open Variation Database)LOVD 3.0 shared installation
DECIPHER (Syndromes)1:92145900-92351836
Mutations and Diseases : HGMDTGFBR3
OMIM600742   
MedgenTGFBR3
GENETestsTGFBR3
Disease Genetic AssociationTGFBR3
Huge Navigator TGFBR3 [HugePedia]  TGFBR3 [HugeCancerGEM]
Genomic VariantsTGFBR3  TGFBR3 [DGVbeta]
Exome VariantTGFBR3
dbVarTGFBR3
ClinVarTGFBR3
snp3D : Map Gene to Disease7049
DGIdb (Curated mutations)TGFBR3
DGIdb (Drug Gene Interaction db)TGFBR3
General knowledge
Homologs : HomoloGeneTGFBR3
Homology/Alignments : Family Browser (UCSC)TGFBR3
Phylogenetic Trees/Animal Genes : TreeFamTGFBR3
Chemical/Protein Interactions : CTD7049
Chemical/Pharm GKB GenePA36487
Clinical trialTGFBR3
Cancer Resource (Charite)ENSG00000069702
Other databases
Other databaseAmerican Cancer Society
Probes
Litterature
PubMed106 Pubmed reference(s) in Entrez
CoreMineTGFBR3
GoPubMedTGFBR3
iHOPTGFBR3

Bibliography

Plasmin cleaves betaglycan and releases a 60 kDa transforming growth factor-beta complex from the cell surface.
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PMID 8068006
 
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The shedding of betaglycan is regulated by pervanadate and mediated by membrane type matrix metalloprotease-1.
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Role of transforming growth factor Beta in human cancer.
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PMID 15774796
 
Haemosiderotic fibrolipomatous tumour (so-called haemosiderotic fibrohistiocytic lipomatous tumour): analysis of 13 new cases in support of a distinct entity.
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Myxoinflammatory fibroblastic sarcoma: investigations by comparative genomic hybridization of two cases and review of the literature.
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PMID 17694321
 
Modulation of NFkappaB activity and E-cadherin by the type III transforming growth factor beta receptor regulates cell growth and motility.
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PMID 17823118
 
The type III TGF-beta receptor suppresses breast cancer progression.
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PMID 17160136
 
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The type III transforming growth factor-beta receptor as a novel tumor suppressor gene in prostate cancer.
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PMID 17283142
 
The type III TGF-beta receptor signals through both Smad3 and the p38 MAP kinase pathways to contribute to inhibition of cell proliferation.
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Carcinogenesis. 2007 Dec;28(12):2491-500. Epub 2007 Sep 3.
PMID 17768179
 
TbetaRIII suppresses non-small cell lung cancer invasiveness and tumorigenicity.
Finger EC, Turley RS, Dong M, How T, Fields TA, Blobe GC.
Carcinogenesis. 2008 Mar;29(3):528-35. Epub 2008 Jan 3.
PMID 18174241
 
Loss of type III transforming growth factor beta receptor expression increases motility and invasiveness associated with epithelial to mesenchymal transition during pancreatic cancer progression.
Gordon KJ, Dong M, Chislock EM, Fields TA, Blobe GC.
Carcinogenesis. 2008 Feb;29(2):252-62. Epub 2007 Nov 13.
PMID 17999987
 
Expression of the type III TGF-beta receptor is negatively regulated by TGF-beta.
Hempel N, How T, Cooper SJ, Green TR, Dong M, Copland JA, Wood CG, Blobe GC.
Carcinogenesis. 2008 May;29(5):905-12. Epub 2008 Feb 24.
PMID 18299279
 
Down-regulation of transforming growth factor beta receptor type III in hepatocellular carcinoma is not directly associated with genetic alterations or loss of heterozygosity.
Bae HJ, Eun JW, Noh JH, Kim JK, Jung KH, Xie HJ, Park WS, Lee JY, Nam SW.
Oncol Rep. 2009 Sep;22(3):475-80.
PMID 19639191
 
The transforming growth factor-beta type III receptor mediates distinct subcellular trafficking and downstream signaling of activin-like kinase (ALK)3 and ALK6 receptors.
Lee NY, Kirkbride KC, Sheu RD, Blobe GC.
Mol Biol Cell. 2009 Oct;20(20):4362-70. Epub 2009 Sep 2.
PMID 19726563
 
The type III TGF-beta receptor regulates epithelial and cancer cell migration through beta-arrestin2-mediated activation of Cdc42.
Mythreye K, Blobe GC.
Proc Natl Acad Sci U S A. 2009 May 19;106(20):8221-6. Epub 2009 May 1.
PMID 19416857
 
The type III transforming growth factor-beta receptor negatively regulates nuclear factor kappa B signaling through its interaction with beta-arrestin2.
You HJ, How T, Blobe GC.
Carcinogenesis. 2009 Aug;30(8):1281-7. Epub 2009 Mar 26.
PMID 19325136
 
Consistent t(1;10) with rearrangements of TGFBR3 and MGEA5 in both myxoinflammatory fibroblastic sarcoma and hemosiderotic fibrolipomatous tumor.
Antonescu CR, Zhang L, Nielsen GP, Rosenberg AE, Dal Cin P, Fletcher CD.
Genes Chromosomes Cancer. 2011 Oct;50(10):757-64. doi: 10.1002/gcc.20897. Epub 2011 Jun 29.
PMID 21717526
 
Type III TGF-b receptor enhances colon cancer cell migration and anchorage-independent growth.
Gatza CE, Holtzhausen A, Kirkbride KC, Morton A, Gatza ML, Datto MB, Blobe GC.
Neoplasia. 2011 Aug;13(8):758-70.
PMID 21847367
 
The type III transforming growth factor-beta receptor inhibits proliferation, migration, and adhesion in human myeloma cells.
Lambert KE, Huang H, Mythreye K, Blobe GC.
Mol Biol Cell. 2011 May;22(9):1463-72. Epub 2011 Mar 16.
PMID 21411633
 
Downregulation of TGF-beta receptor types II and III in oral squamous cell carcinoma and oral carcinoma-associated fibroblasts.
Meng W, Xia Q, Wu L, Chen S, He X, Zhang L, Gao Q, Zhou H.
BMC Cancer. 2011 Feb 28;11:88.
PMID 21352603
 
TbRIII/b-arrestin2 regulates integrin a5b1 trafficking, function, and localization in epithelial cells.
Mythreye K, Knelson EH, Gatza CE, Gatza ML, Blobe GC.
Oncogene. 2012 May 7. doi: 10.1038/onc.2012.157. [Epub ahead of print]
PMID 22562249
 
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Contributor(s)

Written04-2008Catherine E Gatza, Gerard C Blobe
Department of Medicine, Department of Pharmacology and Cancer Biology, Duke University Medical Center, 354 LSRC, B wing, Research Drive, Box 91004, Durham NC 27708, USA
Updated05-2012Catherine E Gatza, David Rawson, Gerard C Blobe
Department of Medicine, Department of Pharmacology and Cancer Biology, Duke University Medical Center, 354 LSRC, B wing, Research Drive, Box 91004, Durham NC 27708, USA

Citation

This paper should be referenced as such :
Gatza, CE ; Rawson, D ; Blobe, GC
TGFBR3 (transforming growth factor, beta receptor III)
Atlas Genet Cytogenet Oncol Haematol. 2012;16(10):736-742.
Free online version   Free pdf version   [Bibliographic record ]
History of this paper:
Gatza, CE ; Rawson, D ; Blobe, GC. TGFBR3 (transforming growth factor, beta receptor III). Atlas Genet Cytogenet Oncol Haematol. 2012;16(10):736-742.
http://documents.irevues.inist.fr/bitstream/handle/2042/48151/1/05-2012-TGFBR3ID42541ch1p33.pdf
URL : http://AtlasGeneticsOncology.org/Genes/TGFBR3ID42541ch1p33.html

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