ID:SMAD7_HUMAN DESCRIPTION: RecName: Full=Mothers against decapentaplegic homolog 7; Short=MAD homolog 7; Short=Mothers against DPP homolog 7; AltName: Full=Mothers against decapentaplegic homolog 8; Short=MAD homolog 8; Short=Mothers against DPP homolog 8; AltName: Full=SMAD family member 7; Short=SMAD 7; Short=Smad7; Short=hSMAD7; 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. 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 (By similarity). SUBUNIT: Interacts with WWP1 (By similarity). Interacts with COPS5. Interacts with NEDD4L. Interacts with STAMBP. Interacts with RNF111, AXIN1 and AXIN2. Interacts with PPP1R15A. Interacts (via MH2 domain) with EP300. Interacts with ACVR1B, SMURF1, SMURF2 and TGFBR1; SMAD7 recruits SMURF1 and SMURF2 to the TGF-beta receptor and regulates its degradation. Interacts with PDPK1 (via PH domain). INTERACTION: Q92905:COPS5; NbExp=10; IntAct=EBI-3861591, EBI-594661; O00308:WWP2; NbExp=5; IntAct=EBI-3861591, EBI-743923; SUBCELLULAR LOCATION: Nucleus. Cytoplasm. Note=Interaction with NEDD4L or RNF111 or induces translocation from the nucleus to the cytoplasm. 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. TISSUE SPECIFICITY: Ubiquitous with higher expression in the lung and vascular endothelium. INDUCTION: By TGFB1. PTM: 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. PTM: Ubiquitinated by WWP1 (By similarity). Polyubiquitinated by RNF111, which is enhanced by AXIN1 and promotes proteasomal degradation. In response to TGF-beta, ubiquitinated by SMURF1; which promotes its degradation. PTM: Acetylation prevents ubiquitination and degradation mediated by SMURF1. DISEASE: Genetic variations in SMAD7 influence susceptibility to colorectal cancer type 3 (CRCS3) [MIM:612229]. Colorectal cancer consists of tumors or cancer of either the colon or rectum or both. Cancers of the large intestine are the second most common form of cancer found in males and females. Symptoms include rectal bleeding, occult blood in stools, bowel obstruction and weight loss. Treatment is based largely on the extent of cancer penetration into the intestinal wall. Surgical cures are possible if the malignancy is confined to the intestine. Risk can be reduced when following a diet which is low in fat and high in fiber. SIMILARITY: Belongs to the dwarfin/SMAD family. SIMILARITY: Contains 1 MH1 (MAD homology 1) domain. SIMILARITY: Contains 1 MH2 (MAD homology 2) domain.
The RNAfold program from the Vienna RNA Package is used to perform the secondary structure predictions and folding calculations. The estimated folding energy is in kcal/mol. The more negative the energy, the more secondary structure the RNA is likely to have.
ModBase Predicted Comparative 3D Structure on O15105
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Orthologous Genes in Other Species
Orthologies between human, mouse, and rat are computed by taking the best BLASTP hit, and filtering out non-syntenic hits. For more distant species reciprocal-best BLASTP hits are used. Note that the absence of an ortholog in the table below may reflect incomplete annotations in the other species rather than a true absence of the orthologous gene.
BioCarta from NCI Cancer Genome Anatomy Project h_tgfbPathway - TGF beta signaling pathway
Reactome (by CSHL, EBI, and GO)
Protein O15105 (Reactome details) participates in the following event(s):
R-HSA-173483 BAMBI interferes with the interaction of type I receptor with type II receptor R-HSA-173512 I-SMAD competes with SMAD2/3 for type I receptor (TGFBR1) R-HSA-2128994 STRAP stabilizes interaction of activated TGF-beta receptor complex with SMAD7 R-HSA-178178 PP1 dephosphorylates TGFBR1 R-HSA-178208 SMAD7 binds to SMURF2 R-HSA-2167917 SMAD7 binds to SMURF1 R-HSA-2176416 NEDD4L ubiquitin ligase binds SMAD7 R-HSA-2186771 RNF111 binds SMAD7 R-HSA-178189 SMAD7 recruits GADD34:PP1 to phosphorylated TGFBR R-HSA-2167876 SMAD7:SMURF2 complex translocates to the cytosol R-HSA-178215 SMAD7:SMURF1 complex is exported to the cytosol R-HSA-178218 SMAD7:SMURF complex binds to phosphorylated TGFBR1 R-HSA-2176417 SMAD7:NEDD4L complex translocates to the cytosol R-HSA-201475 I-Smad competes with R-Smad1/5/8 for type I receptor R-HSA-202626 I-Smad competes with Co-Smad for R-Smad1/5/8 R-HSA-2167924 SMAD7:SMURF1 complex binds XPO1 (CRM1) R-HSA-2186785 RNF111 ubiquitinates SMAD7 R-HSA-2179293 UCHL5 binds SMAD7 in complex with ubiquitinated TGFBR1 R-HSA-2169050 SMURFs/NEDD4L ubiquitinate phosphorylated TGFBR1 and SMAD7 R-HSA-2179291 UCHL5, USP15 deubiquitinate TGFBR1 R-HSA-201821 I-Smad binds to type I receptor, preventing Smad1/5/8 from being activated R-HSA-6781764 USP15 deubiquitinates SMAD1,SMAD2,SMAD3, SMAD7:SMURF,KEAP1 R-HSA-2173788 Downregulation of TGF-beta receptor signaling R-HSA-2173796 SMAD2/SMAD3:SMAD4 heterotrimer regulates transcription R-HSA-201451 Signaling by BMP R-HSA-2173789 TGF-beta receptor signaling activates SMADs R-HSA-2173793 Transcriptional activity of SMAD2/SMAD3:SMAD4 heterotrimer R-HSA-5689603 UCH proteinases R-HSA-9006936 Signaling by TGF-beta family members R-HSA-170834 Signaling by TGF-beta Receptor Complex R-HSA-212436 Generic Transcription Pathway R-HSA-5688426 Deubiquitination R-HSA-5689880 Ub-specific processing proteases R-HSA-162582 Signal Transduction R-HSA-73857 RNA Polymerase II Transcription R-HSA-597592 Post-translational protein modification R-HSA-74160 Gene expression (Transcription) R-HSA-392499 Metabolism of proteins
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Common Gene Haplotype Alleles 
