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Mothers against decapentaplegic homolog 4 : ウィキペディア英語版
Mothers against decapentaplegic homolog 4

SMAD 4, also called SMAD family member n°4 or Mothers against decapentaplegic homolog 4, is a protein involved in cell signaling in mammals. It belongs to the proteins of the SMAD family.
SMAD 4 participates in chain reactions inside cells where it interacts with other members of the SMAD family such as SMAD2 or SMAD3. SMAD 4 forms with SMAD 3 a complex which can bind to DNA and modify the expression of several genes related to cellular activities such as proliferation or differentiation. The complex SMAD 3-SMAD 4 is therefore a transcription factor. Intracellular reactions involving SMAD 4 are triggered by the binding, on the surface of the cells, of growth factors from the TGFβ family. The sequence of intracellular reactions involving SMADS is called the SMAD pathway or the transforming growth factor beta (TGF-β) pathway since the sequence starts with the recognition of TGF-β by cells.

SMAD 4 belongs to the co-SMAD group, the second class of the SMAD family. SMAD 4 is the only known co-SMAD in mammals. It also belongs to the Darwin family of proteins that modulate members of the TGFβ protein superfamily, a family of proteins that all play a role in the regulation of cellular responses. Mammalian SMAD 4 is a homolog of the ''Drosophila'' protein "Mothers against decapentaplegic" or MAD.
== Structure ==

SMAD family member 4 is a 552 amino-acid polypeptide with a molecular weight of 60 439 daltons. This protein is composed of only one chain of amino acids.
SMAD 4 is always coded in mammals by a gene located on chromosome 18. In humans, the protein is coded by the ''SMAD 4'' gene, which is located in the region 21.1 of chromosome 18.〔(【引用サイトリンク】 SMAD4 SMAD family member 4 )〕 The human gene contains 54 829 base pairs and is located from pair n° 51,030,212 to pair 51,085,041.〔(【引用サイトリンク】 work = The Genetics Home Reference Website )
SMAD 4 has a tri-dimensional structure and two functional domains known as MH1 and MH2. The letters M and H stand for MAD Homology and refer to the similarity between mammals SMAD 4 and the ''Drosophilia'' protein ''Mothers against decapentaplegic (MAD)''.
The MH1 domain, corresponding to the N-terminus, contains amino-acids with physical and chemical properties that give SMAD 4 specific DNA-binding properties. This region recognizes a specific DNA sequence composed of eight nucleotides: G-T-C-T-A-G-A-C.
The sequence is also recognized by SMAD 3, which forms a protein complex with SMAD 4 in the cytoplasm of mammalian cells. It is therefore sometimes called the "consensus sequence" but is mostly known as Smad-binding DNA element (SBE). The MH1 domain facilitates the binding of SMAD 4 to receptors such as SMAD 2 and SMAD 3 which belong to the R-SMAD group (first class of the SMAD family) by interacting with their phosphorylated MH2 domain.
The MH2 domain, corresponding to the C-terminus, is responsible for receptor recognition, DNA binding and association with other SMADs. Just as the MH1 domain interacts with the R-SMADS MH2 domain, the SMAD 4 MH2 domain directly interacts with their MH1 domain.〔 SMAD 4 can therefore form with other SMADS heterodimers and heterotrimers.

抄文引用元・出典: フリー百科事典『 ウィキペディア(Wikipedia)
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