SMAD2
SMAD2 (SMAD family member 2) is a protein that switches other genes on and off. The public catalogues list it as a drug target, an oncogene driver, a tumour suppressor and a biomarker, and an approved or late-stage drug is recorded against it. Tied to Colorectal cancer, Skin cancer, Gastric & gastro-oesophageal junction cancer and 1 more.
Overview
Receptor-regulated SMAD (R-SMAD) that is an intracellular signal transducer and transcriptional modulator activated by TGF-beta (transforming growth factor) and activin type 1 receptor kinases. Binds the TRE element in the promoter region of many genes that are regulated by TGF-beta and, on formation of the SMAD2/SMAD4 complex, activates transcription. Promotes TGFB1-mediated transcription of odontoblastic differentiation genes in dental papilla cells.
CIViC holds 1 clinical evidence item and 0 assertions across 1 variant. Open Targets scores its association with cancer at 0.80 (direct and indirect evidence; datatypes literature 0.98, affected pathway 0.76, genetic association 0.59, somatic mutation 0.94). IntOGen calls it a driver in 5 cohorts (2 activating, 3 loss-of-function), covering Colon Adenocarcinoma, Colorectal Adenocarcinoma. In OnCo, 1 product record names it (Luspatercept).
- Target · the protein and the cell it sits on
- Drug · antibody, small molecule, cell or radioligand
- Effect · signal, damage or kill
In plain words · SMAD2 (SMAD family member 2) is a protein that switches other genes on and off. The public catalogues list it as a drug target, an oncogene driver, a tumour suppressor and a biomarker, and an approved or late-stage drug is recorded against it. Tied to Colorectal cancer, Skin cancer, Gastric & gastro-oesophageal junction cancer and 1 more.
- 1 · What it is
SMAD2 (SMAD family member 2) is a protein that switches other genes on and off. The public catalogues list it as a drug target, an oncogene driver, a tumour suppressor and a biomarker, and an approved or late-stage drug is recorded against it. Tied to Colorectal cancer, Skin cancer, Gastric & gastro-oesophageal junction cancer and 1 more.
- 2 · What goes wrong in cancer
Receptor-regulated SMAD (R-SMAD) that is an intracellular signal transducer and transcriptional modulator activated by TGF-beta (transforming growth factor) and activin type 1 receptor kinases.
- 3 · How drugs use it
No product in this corpus aims at SMAD2 yet. Transcription factors have no pocket to plug, so drugs either degrade them or block the partner protein they need to dock on DNA.
External identifiers
Sources: HGNC HGNC:6768 (approved symbol, name, aliases, locus and cross-references (hgnc_complete_set.txt)); UniProt Q15796 (protein name, function text, keywords and locations (REST API)); CIViC gene SMAD2 (1 evidence items, 0 assertions, 1 variants; diseases: (GraphQL API, CC0)); Open Targets ENSG00000175387 (association with cancer (MONDO_0004992) 0.80; per-cancer scores at or above 0.5: colorectal cancer 0.67, gastric cancer 0.52, melanoma 0.55, skin cancer 0.54 (GraphQL API, CC0)); IntOGen SMAD2 (driver in 5 cohorts (Act 2, LoF 3); Compendium_Cancer_Genes.tsv release 20240920, CC0 1.0)
Biology
Receptor-regulated SMAD (R-SMAD) that is an intracellular signal transducer and transcriptional modulator activated by TGF-beta (transforming growth factor) and activin type 1 receptor kinases. Binds the TRE element in the promoter region of many genes that are regulated by TGF-beta and, on formation of the SMAD2/SMAD4 complex, activates transcription. Promotes TGFB1-mediated transcription of odontoblastic differentiation genes in dental papilla cells. Positively regulates PDPK1 kinase activity by stimulating its dissociation from the 14-3-3 protein YWHAQ which acts as a negative regulator. May act as a tumour suppressor in colorectal carcinoma. Location: Cytoplasm; Nucleus (UniProt). Locus 18q21.1 (HGNC).
- Colorectal cancer: Open Targets association 0.67 with colorectal cancer (MONDO_0005575); IntOGen driver in 5 cohorts (COAD, COADREAD)
- Skin cancer: Open Targets association 0.54 with skin cancer (MONDO_0002898)
- Gastric & gastro-oesophageal junction cancer: Open Targets association 0.52 with gastric cancer (MONDO_0001056)
- Melanoma: Open Targets association 0.55 with melanoma (MONDO_0005105)
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: 1 OnCo product record names it; IntOGen calls it an activating (Act) driver in 2 cohorts; IntOGen calls it a loss-of-function (LoF) driver in 3 cohorts; CIViC holds 1 clinical evidence items on its variants. Evidence tier "approved-drug" is the strongest of those signals.
- Prevalence not recorded: none of the sources gives a positivity rate.
Latest papers
topQuery for this target: (TITLE:"SMAD2" OR ABSTRACT:"SMAD2" OR TITLE:"SMAD family member 2" OR ABSTRACT:"SMAD family member 2" OR TITLE:"MADR2" OR ABSTRACT:"MADR2" OR TITLE:"JV18-1" OR ABSTRACT:"JV18-1" OR TITLE:"MADH2" OR ABSTRACT:"MADH2") 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 SMAD2, not a curated reading list.
Similar pages
not linked directly; found by shared links- TargetTGFBR2
Shares TGF-β signalling, IntOGen, Gastric & gastro-oesophageal junction cancer, Open Targets Platform.
- TargetSMAD4
Shares TGF-β signalling, CIViC, IntOGen, Gastric & gastro-oesophageal junction cancer.
- TargetTGFBR1
Shares TGF-β signalling, IntOGen, Open Targets Platform.
- Key paperCOMMANDS: luspatercept versus epoetin alfa as first treatment for anaemia in lower-risk MDS needing transfusions
Shares Luspatercept, TGF-β signalling.
- PathwayGastric cancer (KEGG map)
Shares TGF-β signalling, Gastric & gastro-oesophageal junction cancer.