TGFBR2
TGFBR2 (TGF-beta receptor type-2) is a protein kinase, an enzyme that switches other proteins on by adding phosphate groups. The public catalogues list it as an oncogene driver and a tumour suppressor, and it is called a cancer driver by mutation analysis of patient cohorts. Tied to Colorectal cancer, Oesophageal cancer, Pancreatic ductal adenocarcinoma and 5 more.
Overview
Transmembrane serine/threonine kinase forming with the TGF-beta type I serine/threonine kinase receptor, TGFBR1, the non-promiscuous receptor for the TGF-beta cytokines TGFB1, TGFB2 and TGFB3. Transduces the TGFB1, TGFB2 and TGFB3 signal from the cell surface to the cytoplasm and thus regulates a plethora of physiological and pathological processes including cell cycle arrest in epithelial and haematopoietic cells, control of mesenchymal cell proliferation and differentiation, wound healing, extracellular matrix production, immunosuppression and carcinogenesis. The formation of the receptor complex composed of 2 TGFBR1 and 2 TGFBR2 molecules symmetrically bound to the cytokine dimer results in the phosphorylation and activation of TGFBR1 by the constitutively active TGFBR2.
Open Targets scores its association with cancer at 0.87 (direct and indirect evidence; datatypes genetic literature 0.61, affected pathway 0.87, literature 0.99, genetic association 0.85, somatic mutation 0.95, animal model 0.43). IntOGen calls it a driver in 14 cohorts (3 activating, 11 loss-of-function), covering Renal Clear Cell Carcinoma, Cervical Adenocarcinoma, Cervical Squamous Cell Carcinoma, Colorectal Adenocarcinoma, Oesophageal Adenocarcinoma, Head and Neck Squamous Cell Carcinoma and others.
- Target · the protein and the cell it sits on
- Drug · antibody, small molecule, cell or radioligand
- Effect · signal, damage or kill
In plain words · TGFBR2 (TGF-beta receptor type-2) is a protein kinase, an enzyme that switches other proteins on by adding phosphate groups. The public catalogues list it as an oncogene driver and a tumour suppressor, and it is called a cancer driver by mutation analysis of patient cohorts. Tied to Colorectal cancer, Oesophageal cancer, Pancreatic ductal adenocarcinoma and 5 more.
- 1 · What it is
TGFBR2 (TGF-beta receptor type-2) is a protein kinase, an enzyme that switches other proteins on by adding phosphate groups. The public catalogues list it as an oncogene driver and a tumour suppressor, and it is called a cancer driver by mutation analysis of patient cohorts. Tied to Colorectal cancer, Oesophageal cancer, Pancreatic ductal adenocarcinoma and 5 more.
- 2 · What goes wrong in cancer
Transmembrane serine/threonine kinase forming with the TGF-beta type I serine/threonine kinase receptor, TGFBR1, the non-promiscuous receptor for the TGF-beta cytokines TGFB1, TGFB2 and TGFB3.
- 3 · How drugs use it
No product in this corpus aims at TGFBR2 yet. Kinases are switched on by binding ATP inside the cell, so most drugs are small molecules shaped to plug that ATP pocket.
External identifiers
Sources: HGNC HGNC:11773 (approved symbol, name, aliases, locus and cross-references (hgnc_complete_set.txt)); UniProt P37173 (protein name, function text, keywords and locations (REST API)); Open Targets ENSG00000163513 (association with cancer (MONDO_0004992) 0.87; per-cancer scores at or above 0.5: colorectal cancer 0.72, gastric cancer 0.56, oesophageal cancer 0.68, ovarian cancer 0.51, head and neck squamous cell carcinoma 0.51, breast cancer 0.58 (GraphQL API, CC0)); IntOGen TGFBR2 (driver in 14 cohorts (Act 3, LoF 11); Compendium_Cancer_Genes.tsv release 20240920, CC0 1.0)
Biology
Transmembrane serine/threonine kinase forming with the TGF-beta type I serine/threonine kinase receptor, TGFBR1, the non-promiscuous receptor for the TGF-beta cytokines TGFB1, TGFB2 and TGFB3. Transduces the TGFB1, TGFB2 and TGFB3 signal from the cell surface to the cytoplasm and thus regulates a plethora of physiological and pathological processes including cell cycle arrest in epithelial and haematopoietic cells, control of mesenchymal cell proliferation and differentiation, wound healing, extracellular matrix production, immunosuppression and carcinogenesis. The formation of the receptor complex composed of 2 TGFBR1 and 2 TGFBR2 molecules symmetrically bound to the cytokine dimer results in the phosphorylation and activation of TGFBR1 by the constitutively active TGFBR2. Activated TGFBR1 phosphorylates SMAD2 which dissociates from the receptor and interacts with SMAD4. The SMAD2-SMAD4 complex is subsequently translocated to the nucleus where it modulates the transcription of the TGF-beta-regulated genes. This constitutes the canonical SMAD-dependent TGF-beta signalling cascade. Location: Cell membrane; Membrane raft; Secreted (UniProt). Locus 3p24.1 (HGNC).
- Colorectal cancer: Open Targets association 0.72 with colorectal cancer (MONDO_0005575); IntOGen driver in 1 cohort (COADREAD)
- Oesophageal cancer: Open Targets association 0.68 with oesophageal cancer (MONDO_0007576); IntOGen driver in 1 cohort (ESCA)
- Pancreatic ductal adenocarcinoma: IntOGen driver in 6 cohorts (PAAD, PANCREAS)
- Head and neck squamous cell carcinoma: Open Targets association 0.51 with head and neck squamous cell carcinoma (MONDO_0010150); IntOGen driver in 2 cohorts (HNSC)
- Cervical cancer: IntOGen driver in 2 cohorts (CEAD, CESC)
- Breast cancer: Open Targets association 0.58 with breast cancer (MONDO_0007254)
Notes
top- Written by scripts/fetch-cancer-genes.ts from CIViC, Open Targets, IntOGen, HGNC and UniProt; the function text is UniProt's, condensed and in UK spelling. Roles: IntOGen calls it an activating (Act) driver in 3 cohorts; IntOGen calls it a loss-of-function (LoF) driver in 11 cohorts. Evidence tier "cohort-driver" is the strongest of those signals.
- Prevalence not recorded: none of the sources gives a positivity rate.
Latest papers
topQuery for this target: (TITLE:"TGFBR2" OR ABSTRACT:"TGFBR2" OR TITLE:"transforming growth factor beta receptor 2" OR ABSTRACT:"transforming growth factor beta receptor 2" OR TITLE:"TGF-beta receptor type-2" OR ABSTRACT:"TGF-beta receptor type-2" OR TITLE:"TBRII" OR ABSTRACT:"TBRII" OR TITLE:"TBR-ii" OR ABSTRACT:"TBR-ii" OR TITLE:"MFS2" OR ABSTRACT:"MFS2") AND (cancer OR tumor OR tumour OR oncology OR carcinoma OR lymphoma OR leukemia OR leukaemia OR myeloma OR sarcoma OR melanoma OR glioma). Results are unfiltered search hits about TGFBR2, not a curated reading list.
Similar pages
not linked directly; found by shared links- TargetSMAD4
Shares TGF-β signalling, Oesophageal cancer, Breast cancer (all types), IntOGen.
- TargetTGFBR1
Shares TGF-β signalling, Oesophageal cancer, IntOGen, Open Targets Platform.
- TargetSMAD2
Shares TGF-β signalling, IntOGen, Gastric & gastro-oesophageal junction cancer, Open Targets Platform.
- CompanyIsarna Therapeutics
- TermDesmoplasia (tumour stroma)
- PathwayInvasion: proteases, adhesion & the invasive front
Shares TGF-β signalling, Head and neck squamous cell carcinoma, Pancreatic ductal adenocarcinoma.
- PathwayGastric cancer (KEGG map)
Shares TGF-β signalling, Gastric & gastro-oesophageal junction cancer.