SMAD7
Function
Antagonist of signaling by TGF-beta (transforming growth factor) type 1 receptor superfamily members; has been shown to inhibit TGF-beta (Transforming growth factor) and activin signaling by associating with their receptors thus preventing SMAD2 access (PubMed:21791611). Functions as an adapter to recruit SMURF2 to the TGF-beta receptor complex. Also acts by recruiting the PPP1R15A-PP1 complex to TGFBR1, which promotes its dephosphorylation. Positively regulates PDPK1 kinase activity by stimulating its dissociation from the 14-3-3 protein YWHAQ which acts as a negative regulator.
Involvement in disease
Colorectal cancer 3
CRCS3
A complex disease characterized by malignant lesions arising from the inner wall of the large intestine (the colon) and the rectum. Genetic alterations are often associated with progression from premalignant lesion (adenoma) to invasive adenocarcinoma. Risk factors for cancer of the colon and rectum include colon polyps, long-standing ulcerative colitis, and genetic family history.
None
Disease susceptibility is associated with variants affecting the gene represented in this entry.
Post-translational modifications
Phosphorylation on Ser-249 does not affect its stability, nuclear localization or inhibitory function in TGFB signaling; however it affects its ability to regulate transcription (By similarity). Phosphorylated by PDPK1.
Ubiquitinated by WWP1 (By similarity). Polyubiquitinated by RNF111, which is enhanced by AXIN1 and promotes proteasomal degradation (PubMed:14657019, PubMed:16601693). In response to TGF-beta, ubiquitinated by SMURF1; which promotes its degradation (PubMed:11278251).
Acetylation prevents ubiquitination and degradation mediated by SMURF1.
Sequence Similarities
Belongs to the dwarfin/SMAD family.
Tissue Specificity
Ubiquitous with higher expression in the lung and vascular endothelium.
Cellular localization
- Nucleus
- Cytoplasm
- Interaction with NEDD4L or RNF111 induces translocation from the nucleus to the cytoplasm (PubMed:16601693). TGF-beta stimulates its translocation from the nucleus to the cytoplasm. PDPK1 inhibits its translocation from the nucleus to the cytoplasm in response to TGF-beta (PubMed:17327236).
Alternative names
MADH7, MADH8, SMAD7, Mothers against decapentaplegic homolog 7, MAD homolog 7, Mothers against DPP homolog 7, Mothers against decapentaplegic homolog 8, SMAD family member 7, MAD homolog 8, Mothers against DPP homolog 8, SMAD 7, Smad7, hSMAD7