Mothers against decapentaplegic homolog 3

SMAD3 or Mothers against decapentaplegic homolog 3 is a gene which appears in humans on chromosome 15. It is one of several human homologues of a gene which was originally discovered in the fruit fly Drosophila melanogaster.

The name SMAD3 also refers to a member of the SMAD family of proteins.

SMAD3 gene
The SMAD3 gene codes for the SMAD3 protein. It consists of 9 exons over 129,339 base pairs.

In mice, mutation of SMAD3 has been associated with colorectal adenocarcinoma, increased systemic inflammation, and accelerated wound healing. There is no conclusive evidence of similar activity in humans, however. A 2002 study investigated possible links between SMAD3 mutation and cancer of the pancreas and parathyroid gland, but found no connection. Increased SMAD3 activity has, however, been implicated in the pathogenesis of scleroderma.

The herpes simplex virus can downregulate SMAD3 using the Lat transcription factor, even while the virus is in a latent state.

A reference assembly of SMAD3 is available.

SMAD3 protein
SMAD3 or Mothers against decapentaplegic homolog 3 is a polypeptide that, as its name describes, is a homolog of the Drosophila protein "Mothers against decapentaplegic". It belongs to the SMAD family of proteins, which belong to the TGFβ superfamily of modulators. Like many other TGFβ family members, SMAD3 is involved in cell signalling. SMAD3 modulates signals of activin and TGFβ's. Binding of this protein with SMAD4 enables its transmigration into the nucleus where it forms complexes with other proteins and acts as a transcription factor. SMAD3 is a receptor-regulated SMAD (R-SMAD).

Nomenclature
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 inspired by organizations formed by mothers to oppose social problems, such as Mothers Against Drunk Driving (MADD).

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