SMAD7

The protein encoded by this gene is a nuclear protein that binds the E3 ubiquitin ligase SMURF2. Upon binding, this complex translocates to the cytoplasm, where it interacts with TGF-beta receptor type-1 (TGFBR1), leading to the degradation of both the encoded protein and TGFBR1. Expression of this gene is induced by TGFBR1. Variations in this gene are a cause of susceptibility to colorectal cancer type 3 (CRCS3). Several transcript variants encoding different isoforms have been found for this gene.

SMAD7

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. 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.

Biological Process adherens junction assemblyManual Assertion Based On ExperimentIMP:BHF-UCL
Biological Process anatomical structure morphogenesisManual Assertion Based On ExperimentIBA:GO_Central
Biological Process artery morphogenesisISS:BHF-UCL
Biological Process BMP signaling pathwayManual Assertion Based On ExperimentIBA:GO_Central
Biological Process cell differentiationManual Assertion Based On ExperimentIBA:GO_Central
Biological Process cellular response to leukemia inhibitory factorIEA:Ensembl
Biological Process cellular response to transforming growth factor beta stimulusManual Assertion Based On ExperimentIMP:BHF-UCL
Biological Process negative regulation of BMP signaling pathwayManual Assertion Based On ExperimentIDA:BHF-UCL
Biological Process negative regulation of cell migrationManual Assertion Based On ExperimentTAS:BHF-UCL
Biological Process negative regulation of chondrocyte proliferationIEA:Ensembl
Biological Process negative regulation of DNA-binding transcription factor activityManual Assertion Based On ExperimentIDA:BHF-UCL
Biological Process negative regulation of epithelial to mesenchymal transitionManual Assertion Based On ExperimentTAS:BHF-UCL
Biological Process negative regulation of ossificationIEA:Ensembl
Biological Process negative regulation of pathway-restricted SMAD protein phosphorylationManual Assertion Based On ExperimentIDA:BHF-UCL
Biological Process negative regulation of peptidyl-serine phosphorylationManual Assertion Based On ExperimentIDA:BHF-UCL
Biological Process negative regulation of peptidyl-threonine phosphorylationManual Assertion Based On ExperimentIDA:BHF-UCL
Biological Process negative regulation of protein ubiquitinationManual Assertion Based On ExperimentIDA:BHF-UCL
Biological Process negative regulation of T cell cytokine productionISS:BHF-UCL
Biological Process negative regulation of T-helper 17 cell differentiationISS:BHF-UCL
Biological Process negative regulation of T-helper 17 type immune responseISS:BHF-UCL
Biological Process negative regulation of transcription by competitive promoter bindingManual Assertion Based On ExperimentIDA:BHF-UCL
Biological Process negative regulation of transcription by RNA polymerase IIManual Assertion Based On ExperimentIDA:BHF-UCL
Biological Process negative regulation of transforming growth factor beta receptor signaling pathwayManual Assertion Based On ExperimentIDA:BHF-UCL
Biological Process negative regulation of ubiquitin-protein transferase activityManual Assertion Based On ExperimentIDA:BHF-UCL
Biological Process pathway-restricted SMAD protein phosphorylationISS:BHF-UCL
Biological Process positive regulation of cell-cell adhesionManual Assertion Based On ExperimentIDA:BHF-UCL
Biological Process positive regulation of chondrocyte hypertrophyIEA:Ensembl
Biological Process positive regulation of proteasomal ubiquitin-dependent protein catabolic processManual Assertion Based On ExperimentIDA:BHF-UCL
Biological Process positive regulation of protein ubiquitinationManual Assertion Based On ExperimentIDA:BHF-UCL
Biological Process protein stabilizationManual Assertion Based On ExperimentIDA:BHF-UCL
Biological Process protein-containing complex localizationManual Assertion Based On ExperimentIDA:BHF-UCL
Biological Process regulation of activin receptor signaling pathwayManual Assertion Based On ExperimentIDA:BHF-UCL
Biological Process regulation of cardiac muscle contractionISS:BHF-UCL
Biological Process regulation of epithelial to mesenchymal transitionManual Assertion Based On ExperimentIMP:BHF-UCL
Biological Process regulation of transforming growth factor beta receptor signaling pathway1 PublicationIC:BHF-UCL
Biological Process regulation of ventricular cardiac muscle cell membrane depolarization1 PublicationIC:BHF-UCL
Biological Process response to laminar fluid shear stressManual Assertion Based On ExperimentIEP:BHF-UCL
Biological Process SMAD protein signal transductionManual Assertion Based On ExperimentIBA:GO_Central
Biological Process transforming growth factor beta receptor signaling pathwayManual Assertion Based On ExperimentIBA:GO_Central
Biological Process ureteric bud developmentIEA:Ensembl
Biological Process ventricular cardiac muscle tissue morphogenesisISS:BHF-UCL
Biological Process ventricular septum morphogenesisISS:BHF-UCL

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).

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.

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.