SMAD2

Description

The SMAD2 (SMAD family member 2) is a protein-coding gene located on chromosome 18.

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. 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.

== Function == 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.

SMAD2, a receptor-regulated SMAD (R-SMAD), acts as an intracellular signal transducer and transcriptional modulator activated by TGF-beta (transforming growth factor) and activin type 1 receptor kinases. It binds to the TRE element in the promoter region of many genes regulated by TGF-beta, activating transcription upon formation of the SMAD2/SMAD4 complex. SMAD2 promotes TGFB1-mediated transcription of odontoblastic differentiation genes in dental papilla cells. It positively regulates PDPK1 kinase activity by stimulating its dissociation from the 14-3-3 protein YWHAQ, which acts as a negative regulator. SMAD2 may act as a tumor suppressor in colorectal carcinoma.

SMAD2 is also known as CHTD8, JV18, JV18-1, LDS6, MADH2, MADR2, hMAD-2, hSMAD2.

Associated Diseases

• Familial thoracic aortic aneurysm and aortic dissection
• Loeys-Dietz syndrome
• Congenital heart defects, multiple types, 8, with or without heterotaxy
• Loeys-Dietz syndrome 6