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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.
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.
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.
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.
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.
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.
First described 1992. Earliest sequence paper UniProt cites for the protein: Lin H.Y. et al, Cell, 1992, "Expression cloning of the TGF-beta type II receptor, a functional transmembrane serine/threonine kinase". Source.
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)
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).
| Cancer | Prevalence | Measure | Note | Source |
|---|---|---|---|---|
| Colorectal cancer | 3-10% | Frameshift of the polyadenine coding microsatellite | cBioPortal: 416 of 7,237, 5.7%, in crc_msk_2026; 47 of 1,134, 4.1%, in crc_msk_2017; 59 of 1,516, 3.9%, in crc_eo_2020; 23 of 224, 10.3%, in coadread_tcga_pub; 19 of 534, 3.6%, in coadread_tcga_pan_can_atlas_2018; 29 of 619, 4.7%, in coadread_dfci_2016. Eight of the first colon cancer cell lines with high microsatellite instability carried TGFBR2 mutations clustered in short repeated sequences, with no surface receptor and little transcript (Markowitz 1995). | cBioPortal (TCGA) |
Approximate, population-level figures; the measure column says what was counted. Ranges show the midpoint as a bar.
It gives surveillance a target and a timetable: catch high-grade dysplasia and there are about three years before invasion, and TGF-beta pathway loss is the event to detect.
It is the reference multi-platform dataset and the reason a KRAS wild-type report is treated as a search for another driver rather than as an absence.
It made TGF-beta the central target of the microsatellite-stable half of the disease, which is the line that leads to Tauriello's immune-evasion work and to the TGF-beta plus checkpoint combinations in trials.
The APGI cohort became the backbone of the QCMG whole-genome and subtype papers; ATM's entry here is the origin of its place on today's germline panels.
It showed how mismatch repair failure selects for cancer: coding microsatellites in tumour suppressors are the targets, which is why TGFBR2, ACVR2A, RNF43 and B2M frameshifts are the signature of MSI-high bowel cancer.
Query 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.
Shares TGF-β signalling, Mismatch repair & microsatellite instability, IntOGen, Gastric & gastro-oesophageal junction cancer.
Shares Genomic characterization of malignant progression in neoplastic pancreatic cysts, Integrated genomic characterization of pancreatic ductal adenocarcinoma, Oesophageal cancer, IntOGen.
Shares Pancreatic cancer genomes reveal aberrations in axon guidance pathway genes, Integrated genomic characterization of pancreatic ductal adenocarcinoma, IntOGen, Gastric & gastro-oesophageal junction cancer.
Shares Integrated genomic characterization of pancreatic ductal adenocarcinoma, Oesophageal cancer, IntOGen, Gastric & gastro-oesophageal junction cancer.
Shares TGF-β signalling, IntOGen, Gastric & gastro-oesophageal junction cancer, Open Targets Platform.
Shares Genomic characterization of malignant progression in neoplastic pancreatic cysts, Pancreatic cancer genomes reveal aberrations in axon guidance pathway genes, Integrated genomic characterization of pancreatic ductal adenocarcinoma, TGF-β signalling.
Shares TGF-β signalling, Oesophageal cancer, IntOGen, Open Targets Platform.
Shares Stromal gene expression defines poor-prognosis subtypes in colorectal cancer, TGF-β signalling, Open Targets Platform, Colorectal cancer.