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)

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

General

nuclear protein phosphoprotein SMAD protein

Properties

SIZE: entity length = 426 aa MW = 46 kD COMPARTMENT: cytoplasm cell nucleus MOTIF: glycine-rich region {27-35} glycine-rich region {49-56} MH1 domain {64-207} proline-rich region SITE: 207-210 MOTIF: proline residue (SEVERAL) Important for interaction with SMURF2 {208-217} MOTIF: PY {208-211} Ser phosphorylation site {S249} MH2 domain {261-426}

References

UniProt :accession O15105

Databases & Figures

OMIM correlations MORBIDMAP 602932 UniProt O15105 PFAM correlations Entrez Gene 4092 Kegg hsa:4092 TGF-beta/BMP signaling