SMAD7/MADH7; mothers against decapentaplegic homolog 7; mothers against DPP homolog 7; MAD homolog 7; SMAD family member 7; SMAD 7; smad7; hSMAD7; mothers against decapentaplegic homolog 8; mothers against DPP homolog 8; MAD homolog 8 (SMAD7, MADH7, MADH8)
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Function
- antagonist of signaling by TGF-beta type 1 receptor superfamily members
- inhibits TGF-beta & activin signaling by associating with their receptors thus preventing SMAD2 access
- functions as an adapter to recruit SMURF2 to the TGF-beta receptor complex
- may inhibit phosphorylation of SMAD2 & SMAD3 by TGF-beta receptor 1
- also acts by recruiting the PPP1R15A-PP1 complex to TGFBR1, which promotes its dephosphorylation
- 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
- polyubiquitinated by RNF111, which is enhanced by AXIN1 & promotes proteasomal degradation
- in response to TGF-beta, ubiquitinated by SMURF1; which promotes its degradation
- acetylation prevents ubiquitination & degradation mediated by SMURF1
- interacts with TGF-beta type 1 receptor
- interacts with COPS5
- interacts with NEDD4L
- interacts with STAMBP
- interacts with RNF111, AXIN1 & AXIN2
- interacts with PPP1R15A
- interacts (via MH2 domain) with EP300
- interacts with SMURF2
Structure
- belongs to the dwarfin/SMAD family
- contains 1 MH1 (MAD homology 1) domain
- contains 1 MH2 (MAD homology 2) domain
Compartment
- nucleus, cytoplasm
- interaction with NEDD4L or RNF111 induces translocation from the nucleus to the cytoplasm
Expression
- ubiquitous with higher expression in the lung & vascular endothelium
- induced by TGF-beta
Pathology
- genetic variations in SMAD7 influence susceptibility to colorectal cancer type 3