Mothers against decapentaplegic homolog 3

Mothers against decapentaplegic homolog 3
SMAD family member 3

PDB rendering based on 1dev.
Symbols SMAD3; DKFZp586N0721; DKFZp686J10186; HSPC193; HsT17436; JV15-2; MADH3; MGC60396
External IDs OMIM603109 MGI1201674 HomoloGene55937 GeneCards: SMAD3 Gene
RNA expression pattern
PBB GE SMAD3 205396 at tn.png
PBB GE SMAD3 205397 x at tn.png
PBB GE SMAD3 205398 s at tn.png
More reference expression data
Species Human Mouse
Entrez 4088 17127
Ensembl ENSG00000166949 ENSMUSG00000032402
UniProt P84022 Q3V3E0
RefSeq (mRNA) NM_001145102.1 NM_016769.4
RefSeq (protein) NP_001138574.1 NP_058049.3
Location (UCSC) Chr 15:
67.36 – 67.49 Mb
Chr 9:
63.49 – 63.61 Mb
PubMed search [1] [2]

Mothers against decapentaplegic homolog 3 also known as SMAD family member 3 or SMAD3 is a protein that in humans is encoded by the SMAD3 gene.[1][2] SMAD3 is a member of the SMAD family of proteins.

The human SMAD3 gene is located on chromosome 15. It is one of several human homologues of a gene that was originally discovered in the fruit fly Drosophila melanogaster.


SMAD3 gene

The human SMAD3 gene is composed of 9 exons over 129,339 base pairs.

In mice, mutation of SMAD3 has been linked to colorectal adenocarcinoma,[3] increased systemic inflammation, and accelerated wound healing.[4] 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. Smad3 is also a multifaceted regulator in adipose physiology and the pathogenesis of obesity and type 2 diabetes. Smad3-knockout mice have diminished adiposity[5], with improved glucose tolerance and insulin sensitivity. Despite their reduced physical activity arising from muscle atrophy[6], these Smad3-knockout mice are resistant to high-fat-diet induced obesity.

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).


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).


  1. ^ "Entrez Gene: SMAD3 SMAD family member 3". 
  2. ^ Zhang Y, Feng X, We R, Derynck R (September 1996). "Receptor-associated Mad homologues synergize as effectors of the TGF-beta response". Nature 383 (6596): 168–72. doi:10.1038/383168a0. PMID 8774881. 
  3. ^ Zhu Y, Richardson JA, Parada LF, Graff JM (September 1998). "Smad3 mutant mice develop metastatic colorectal cancer". Cell 94 (6): 703–14. doi:10.1016/S0092-8674(00)81730-4. PMID 9753318. 
  4. ^ Ashcroft GS, Yang X, Glick AB, Weinstein M, Letterio JL, Mizel DE, Anzano M, Greenwell-Wild T, Wahl SM, Deng C, Roberts AB (September 1999). "Mice lacking Smad3 show accelerated wound healing and an impaired local inflammatory response". Nat. Cell Biol. 1 (5): 260–6. doi:10.1038/12971. PMID 10559937. 
  5. ^ Tan et al. (February 2011). "Smad3 deficiency in mice protects against insulin resistance and obesity induced by a high-fat diet". Diabetes 60 (2): 464–476. doi:10.2337/db10-0801. PMID 21270259. 
  6. ^ Ge et al. (April 2011). "Smad3 signaling is required for satellite cell function and myogenic differentiation of myoblasts". Cell Res.. doi:10.1038/cr.2011.72. PMID 21502976. 

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