Mothers against decapentaplegic homolog 2

Mothers against decapentaplegic homolog 2
SMAD family member 2

PDB rendering based on 1dev.
Symbols SMAD2; JV18; JV18-1; MADH2; MADR2; MGC22139; MGC34440; hMAD-2; hSMAD2
External IDs OMIM601366 MGI108051 HomoloGene21197 GeneCards: SMAD2 Gene
RNA expression pattern
PBB GE SMAD2 203075 at tn.png
PBB GE SMAD2 203076 s at tn.png
PBB GE SMAD2 203077 s at tn.png
More reference expression data
Species Human Mouse
Entrez 4087 17126
Ensembl ENSG00000175387 ENSMUSG00000024563
UniProt Q15796 Q8C2P1
RefSeq (mRNA) NM_001003652.2 NM_010754.4
RefSeq (protein) NP_001003652.1 NP_034884.2
Location (UCSC) Chr 18:
45.36 – 45.46 Mb
Chr 18:
76.4 – 76.47 Mb
PubMed search [1] [2]

Mothers against decapentaplegic homolog 2 also known as SMAD family member 2 or SMAD2 is a protein that in humans is encoded by the SMAD2 gene.[1][2] MAD homolog 2 belongs to the SMAD, a family of proteins similar to the gene products of the Drosophila gene 'mothers against decapentaplegic' (Mad) and the C. elegans gene Sma. SMAD proteins are signal transducers and transcriptional modulators that mediate multiple signaling pathways.



SMAD2 mediates the signal of the transforming growth factor (TGF)-beta, and thus regulates multiple cellular processes, such as cell proliferation, apoptosis, and differentiation. This protein is recruited to the TGF-beta receptors through its interaction with the SMAD anchor for receptor activation (SARA) protein. In response to TGF-beta signal, this protein is phosphorylated by the TGF-beta receptors. The phosphorylation induces the dissociation of this protein with SARA and the association with the family member SMAD4. The association with SMAD4 is important for the translocation of this protein into the cell nucleus, where it binds to target promoters and forms a transcription repressor complex with other cofactors. This protein can also be phosphorylated by activin type 1 receptor kinase, and mediates the signal from the activin. Alternatively spliced transcript variants encoding the same protein have been observed.[3]

Like other Smads, Smad2 plays a role in the transmission of extracellular signals from ligands of the Transforming Growth Factor beta (TGFβ) superfamily of growth factors into the cell nucleus. Binding of a subgroup of TGFβ superfamily ligands to extracellular receptors triggers phosphorylation of Smad2 at a Serine-Serine-Methionine-Serine (SSMS) motif at its extreme C-terminus. Phosphorylated Smad2 is then able to form a complex with Smad4. These complexes accumulate in the cell nucleus, where they are directly participating in the regulation of gene expression.


The SMAD proteins are homologs of both the drosophila protein, mothers against decapentaplegic (MAD) and the C. elegans protein SMA. The name is a combination of the two. During Drosophila research, it was found that a mutation in the gene MAD in the mother repressed the gene decapentaplegic in the embryo. The phrase "Mothers against" was added, since mothers often form organizations opposing various issues, e.g., Mothers Against Drunk Driving, or (MADD). The nomenclature for this protein, like that of Sonic hedgehog, has been criticized for its frivolity[by whom?].


Mothers against decapentaplegic homolog 2 has been shown to interact with:


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This article incorporates text from the United States National Library of Medicine, which is in the public domain.

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