SMAD2 (mothers against decapentaplegic homolog 2 (Drosophila))
2004-07-01 Raphael Saffroy , Antoinette Lemoine , Brigitte Debuire AffiliationService de Biochimie et Biologie moleculaire, Hopital Paul Brousse, Faculte de Medecine Paris Sud, 94 800 Villejuif, France
Identity
HGNC
LOCATION
18q21.1
IMAGE
LEGEND
Probe(s) - Courtesy Mariano Rocchi, Resources for Molecular Cytogenetics
LOCUSID
ALIAS
JV18,JV18-1,MADH2,MADR2,hMAD-2,hSMAD2
FUSION GENES
DNA/RNA
Description
The gene encompasses 90 kb of DNA; 12 exons.
Transcription
2285 nucleotides mRNA. Alternative splicing was described.
Proteins
Description
467 amino acids; 52 kDa protein. A short 438 amino acids isoform was also described. Smad2 belongs to the Darfwin proteins family which are composed of two conserved amino- and carboxyl-terminal domains known as MH1 and MH2, respectively.
Expression
High expression levels in skeletal muscle, heart and placenta.
Function
Smad2 is an intracellular mediator of TGF-beta family and activin type 1 receptor. Smad2 mediate TGF-beta signaling to regulate cell growth and differentiation. Smad2 is released from cytoplasmic retention by TGF-beta receptor-mediated phosphorylation. The phosphorylated Smad2 then forms a heterodimeric complex with Smad4, and this complex translocates from cytoplasm into nucleus. By interacting with DNA-binding proteins, Smad complexes then positively or negatively regulate the transcription of target genes.
Homology
With the other members of the Darfwin/Smad family.
Implicated in
Disease
Colorectal cancers
Oncogenesis
Smad2 was proposed to be a tumor suppressor gene that may function to disrupt TGF-beta signaling. Inactivating mutations in Smad2 have been found in various cancer including colorectal carcinomas. The majority of tumor-derived mutations cluster in the carboxy-terminal MH2 domain, and some of these have been shown to disrupt TGF-beta signaling by blocking receptor-dependent phosphorylation or by preventing heterodimeric interactions between Smads. A mutation at position 133 in the amino-terminal MH1 domain has also been associated with colorectal carcinoma. Nevertheless, loss of Smad2 activation and/or expression was related to occur in less than 10% of colorectal cancers.
Article Bibliography
| Pubmed ID | Last Year | Title | Authors |
|---|---|---|---|
| 8756346 | 1996 | A novel mesoderm inducer, Madr2, functions in the activin signal transduction pathway. | Baker JC et al |
| 8752209 | 1996 | MADR2 maps to 18q21 and encodes a TGFbeta-regulated MAD-related protein that is functionally mutated in colorectal carcinoma. | Eppert K et al |
| 11043574 | 2000 | Identification and characterization of constitutively active Smad2 mutants: evaluation of formation of Smad complex and subcellular distribution. | Funaba M et al |
| 8980228 | 1996 | MADR2 is a substrate of the TGFbeta receptor and its phosphorylation is required for nuclear accumulation and signaling. | Macías-Silva M et al |
| 12894231 | 2003 | Loss of expression, and mutations of Smad 2 and Smad 4 in human cervical cancer. | Maliekal TT et al |
| 9006934 | 1997 | Identification of Smad2, a human Mad-related protein in the transforming growth factor beta signaling pathway. | Nakao A et al |
| 10438456 | 1999 | Evidence that Smad2 is a tumor suppressor implicated in the control of cellular invasion. | Prunier C et al |
| 8673135 | 1996 | Mad-related genes in the human. | Riggins GJ et al |
| 10819637 | 2000 | Mutation analysis of SMAD2, SMAD3, and SMAD4 genes in hereditary non-polyposis colorectal. | Roth S et al |
| 9820171 | 1998 | Somatic alterations of the SMAD-2 gene in human colorectal cancers. | Takagi Y et al |
| 9635866 | 1998 | Mutation analysis of the Smad2 gene in human colon cancers using genomic DNA and intron primers. | Takenoshita S et al |
| 8971158 | 1996 | Somatic in vivo alterations of the JV18-1 gene at 18q21 in human lung cancers. | Uchida K et al |
| 9529255 | 1998 | Smad2 signaling in extraembryonic tissues determines anterior-posterior polarity of the early mouse embryo. | Waldrip WR et al |
| 10615055 | 2000 | Structural basis of Smad2 recognition by the Smad anchor for receptor activation. | Wu G et al |
| 11779503 | 2001 | Crystal structure of a phosphorylated Smad2. Recognition of phosphoserine by the MH2 domain and insights on Smad function in TGF-beta signaling. | Wu JW et al |
| 12967141 | 2003 | Loss of Smad signaling in human colorectal cancer is associated with advanced disease and poor prognosis. | Xie W et al |
| 10781087 | 2000 | Mutations in the tumor suppressors Smad2 and Smad4 inactivate transforming growth factor beta signaling by targeting Smads to the ubiquitin-proteasome pathway. | Xu J et al |
| 12191473 | 2002 | Smad2 nucleocytoplasmic shuttling by nucleoporins CAN/Nup214 and Nup153 feeds TGFbeta signaling complexes in the cytoplasm and nucleus. | Xu L et al |
| 10490821 | 1999 | Smad2 and Smad4 gene mutations in hepatocellular carcinoma. | Yakicier MC et al |
Other Information
Locus ID:
NCBI: 4087
MIM: 601366
HGNC: 6768
Ensembl: ENSG00000175387
Variants:
dbSNP: 4087
ClinVar: 4087
TCGA: ENSG00000175387
COSMIC: SMAD2
RNA/Proteins
Expression (GTEx)
Pathways
Protein levels (Protein atlas)
References
| Pubmed ID | Year | Title | Citations |
|---|---|---|---|
| 37739089 | 2024 | BRD9-SMAD2/3 Orchestrates Stemness and Tumorigenesis in Pancreatic Ductal Adenocarcinoma. | 3 |
| 37755664 | 2024 | Exosomes Derived from Human Adipose Mesenchymal Stem Cells Inhibits Fibrosis and Treats Oral Submucous Fibrosis via the miR-181a-5p/Smad2 Axis. | 3 |
| 38383842 | 2024 | MAP4K4 and WT1 mediate SOX6-induced cellular senescence by synergistically activating the ATF2-TGFβ2-Smad2/3 signaling pathway in cervical cancer. | 0 |
| 38411267 | 2024 | TMED3 stabilizes SMAD2 by counteracting NEDD4-mediated ubiquitination to promote ovarian cancer. | 0 |
| 38495810 | 2024 | DUSP22 Ameliorates Endothelial-to-Mesenchymal Transition in HUVECs through Smad2/3 and MAPK Signaling Pathways. | 0 |
| 38789630 | 2024 | Exosomes derived from adipose tissue-derived stem cells alleviated H(2)O(2)-induced oxidative stress and endothelial-to-mesenchymal transition in human umbilical vein endothelial cells by inhibition of the mir-486-3p/Sirt6/Smad signaling pathway. | 0 |
| 37739089 | 2024 | BRD9-SMAD2/3 Orchestrates Stemness and Tumorigenesis in Pancreatic Ductal Adenocarcinoma. | 3 |
| 37755664 | 2024 | Exosomes Derived from Human Adipose Mesenchymal Stem Cells Inhibits Fibrosis and Treats Oral Submucous Fibrosis via the miR-181a-5p/Smad2 Axis. | 3 |
| 38383842 | 2024 | MAP4K4 and WT1 mediate SOX6-induced cellular senescence by synergistically activating the ATF2-TGFβ2-Smad2/3 signaling pathway in cervical cancer. | 0 |
| 38411267 | 2024 | TMED3 stabilizes SMAD2 by counteracting NEDD4-mediated ubiquitination to promote ovarian cancer. | 0 |
| 38495810 | 2024 | DUSP22 Ameliorates Endothelial-to-Mesenchymal Transition in HUVECs through Smad2/3 and MAPK Signaling Pathways. | 0 |
| 38789630 | 2024 | Exosomes derived from adipose tissue-derived stem cells alleviated H(2)O(2)-induced oxidative stress and endothelial-to-mesenchymal transition in human umbilical vein endothelial cells by inhibition of the mir-486-3p/Sirt6/Smad signaling pathway. | 0 |
| 36226468 | 2023 | SMAD2/3 Phosphorylation Is Downregulated in T Cells in HIV-Infected Patients. | 0 |
| 36335471 | 2023 | APOBEC3B expression is promoted by lincNMR collaborating with TGF-β-Smad pathway. | 2 |
| 36345938 | 2023 | The TGF-β/Smad(2/3) signaling pathway is involved in Musashi2-induced invasion and metastasis of colorectal cancer. | 1 |
Citation
Raphael Saffroy ; Antoinette Lemoine ; Brigitte Debuire
SMAD2 (mothers against decapentaplegic homolog 2 (Drosophila))
Atlas Genet Cytogenet Oncol Haematol. 2004-07-01
Online version: http://atlasgeneticsoncology.org/gene/370/smad2
