Mothers against decapentaplegic homolog 7

SMAD family member 7
Solution Structure Of Smurf2 Ww3 Domain-Smad7 Py Peptide Complex
Identifiers
Symbols	SMAD7; CRCS3; FLJ16482; MADH7; MADH8
External IDs	OMIM: 602932 MGI: 1100518 HomoloGene: 4314 GeneCards: SMAD7 Gene
Gene Ontology Molecular function • protein binding • collagen binding • beta-catenin binding • transforming growth factor beta receptor, inhibitory cytoplasmic mediator activity • ubiquitin protein ligase binding • type I transforming growth factor beta receptor binding • transcription regulatory region DNA binding • activin binding • I-SMAD binding Cellular component • intracellular • nucleus • transcription factor complex • nucleolus • nucleolus • cytoplasm • centrosome • cytosol • cytosol • plasma membrane • cell-cell adherens junction • catenin complex Biological process • negative regulation of transcription from RNA polymerase II promoter • ureteric bud development • transforming growth factor beta receptor signaling pathway • negative regulation of epithelial to mesenchymal transition • negative regulation of epithelial to mesenchymal transition • negative regulation of peptidyl-threonine phosphorylation • negative regulation of transcription by competitive promoter binding • regulation of transforming growth factor beta receptor signaling pathway • positive regulation of cell-cell adhesion • negative regulation of cell migration • BMP signaling pathway • negative regulation of transforming growth factor beta receptor signaling pathway • negative regulation of BMP signaling pathway • negative regulation of protein ubiquitination • positive regulation of protein ubiquitination • positive regulation of proteasomal ubiquitin-dependent protein catabolic process • regulation of activin receptor signaling pathway • negative regulation of peptidyl-serine phosphorylation • adherens junction assembly • response to laminar fluid shear stress • cellular protein complex localization • negative regulation of sequence-specific DNA binding transcription factor activity • positive regulation of anti-apoptosis • artery morphogenesis • protein stabilization • negative regulation of ubiquitin-protein ligase activity • ventricular cardiac muscle tissue morphogenesis • regulation of cardiac muscle contraction • regulation of ventricular cardiomyocyte membrane depolarization • pathway-restricted SMAD protein phosphorylation • negative regulation of pathway-restricted SMAD protein phosphorylation • negative regulation of pathway-restricted SMAD protein phosphorylation • ventricular septum morphogenesis Sources: Amigo / QuickGO
RNA expression pattern
More reference expression data
Orthologs
Species	Human	Mouse
Entrez	4092	17131
Ensembl	ENSG00000101665	ENSMUSG00000025880
UniProt	O15105	n/a
RefSeq (mRNA)	NM_001190821.1	NM_001042660.1
RefSeq (protein)	NP_001177750.1	NP_001036125.1
Location (UCSC)	Chr 18: 46.45 – 46.48 Mb	Chr 18: 75.53 – 75.56 Mb
PubMed search	[1]	[2]

Mothers against decapentaplegic homolog 7 or SMAD7 is a protein that in humans is encoded by the SMAD7 gene.^[1]

SMAD7 is a protein that, as its name describes, is a homolog of the Drosophila gene: "Mothers against decapentaplegic". It belongs to the SMAD family of proteins, which belong to the TGFβ superfamily of ligands. Like many other TGFβ family members, SMAD7 is involved in cell signalling. It is a TGFβ type 1 receptor antagonist. It blocks TGFβ1 and activin associating with the receptor, blocking access to SMAD2. It is an inhibitory SMAD (I-SMAD) and is enhanced by SMURF2.

Smad7 enhances muscle differentiation.

Interactions

Mothers against decapentaplegic homolog 7 has been shown to interact with Mothers against decapentaplegic homolog 6,^[2] Beta-catenin,^[3] RNF111,^[4] TGF beta receptor 1,^{[4][5][6][7][8][9]} YAP1,^[10] MAP3K7IP1,^[11][12] SMURF2,^[6][7][13] PIAS4,^[14] EP300,^[15] STRAP^[9] and Mothers against decapentaplegic homolog 3.^[9][16]

References

1. ^ "Entrez Gene: SMAD7 SMAD family member 7". http://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=4092. 
2. ^ Topper, J N; Cai J, Qiu Y, Anderson K R, Xu Y Y, Deeds J D, Feeley R, Gimeno C J, Woolf E A, Tayber O, Mays G G, Sampson B A, Schoen F J, Gimbrone M A, Falb D (Aug. 1997). "Vascular MADs: Two novel MAD-related genes selectively inducible by flow in human vascular endothelium". Proc. Natl. Acad. Sci. U.S.A. (UNITED STATES) 94 (17): 9314–9. doi:10.1073/pnas.94.17.9314. ISSN 0027-8424. PMC 23174. PMID 9256479. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=23174. 
3. ^ Edlund, Sofia; Lee So Young, Grimsby Susanne, Zhang Shouthing, Aspenström Pontus, Heldin Carl-Henrik, Landström Maréne (Feb. 2005). "Interaction between Smad7 and β-Catenin: Importance for Transforming Growth Factor β-Induced Apoptosis". Mol. Cell. Biol. (United States) 25 (4): 1475–88. doi:10.1128/MCB.25.4.1475-1488.2005. ISSN 0270-7306. PMC 548008. PMID 15684397. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=548008. 
4. ^ ^{a b} Koinuma, Daizo; Shinozaki Masahiko, Komuro Akiyoshi, Goto Kouichiro, Saitoh Masao, Hanyu Aki, Ebina Masahito, Nukiwa Toshihiro, Miyazawa Keiji, Imamura Takeshi, Miyazono Kohei (Dec. 2003). "Arkadia amplifies TGF-β superfamily signalling through degradation of Smad7". EMBO J. (England) 22 (24): 6458–70. doi:10.1093/emboj/cdg632. ISSN 0261-4189. PMC 291827. PMID 14657019. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=291827. 
5. ^ Mochizuki, Toshiaki; Miyazaki Hideyo, Hara Takane, Furuya Toshio, Imamura Takeshi, Watabe Tetsuro, Miyazono Kohei (Jul. 2004). "Roles for the MH2 domain of Smad7 in the specific inhibition of transforming growth factor-beta superfamily signaling". J. Biol. Chem. (United States) 279 (30): 31568–74. doi:10.1074/jbc.M313977200. ISSN 0021-9258. PMID 15148321. 
6. ^ ^{a b} Asano, Yoshihide; Ihn Hironobu, Yamane Kenichi, Kubo Masahide, Tamaki Kunihiko (Jan. 2004). "Impaired Smad7-Smurf–mediated negative regulation of TGF-β signaling in scleroderma fibroblasts". J. Clin. Invest. (United States) 113 (2): 253–64. doi:10.1172/JCI16269. ISSN 0021-9738. PMC 310747. PMID 14722617. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=310747. 
7. ^ ^{a b} Kavsak, P; Rasmussen R K, Causing C G, Bonni S, Zhu H, Thomsen G H, Wrana J L (Dec. 2000). "Smad7 binds to Smurf2 to form an E3 ubiquitin ligase that targets the TGF beta receptor for degradation". Mol. Cell (United States) 6 (6): 1365–75. doi:10.1016/S1097-2765(00)00134-9. ISSN 1097-2765. PMID 11163210. 
8. ^ Hayashi, H; Abdollah S, Qiu Y, Cai J, Xu Y Y, Grinnell B W, Richardson M A, Topper J N, Gimbrone M A, Wrana J L, Falb D (Jun. 1997). "The MAD-related protein Smad7 associates with the TGFbeta receptor and functions as an antagonist of TGFbeta signaling". Cell (UNITED STATES) 89 (7): 1165–73. doi:10.1016/S0092-8674(00)80303-7. ISSN 0092-8674. PMID 9215638. 
9. ^ ^{a b c} Datta, P K; Moses H L (May. 2000). "STRAP and Smad7 Synergize in the Inhibition of Transforming Growth Factor β Signaling". Mol. Cell. Biol. (UNITED STATES) 20 (9): 3157–67. doi:10.1128/MCB.20.9.3157-3167.2000. ISSN 0270-7306. PMC 85610. PMID 10757800. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=85610. 
10. ^ Ferrigno, Olivier; Lallemand François, Verrecchia Franck, L'Hoste Sébastien, Camonis Jacques, Atfi Azeddine, Mauviel Alain (Jul. 2002). "Yes-associated protein (YAP65) interacts with Smad7 and potentiates its inhibitory activity against TGF-beta/Smad signaling". Oncogene (England) 21 (32): 4879–84. doi:10.1038/sj.onc.1205623. ISSN 0950-9232. PMID 12118366. 
11. ^ Edlund, Sofia; Bu Shizhong, Schuster Norbert, Aspenström Pontus, Heuchel Rainer, Heldin Nils-Erik, ten Dijke Peter, Heldin Carl-Henrik, Landström Maréne (Feb. 2003). "Transforming Growth Factor-β1 (TGF-β)–induced Apoptosis of Prostate Cancer Cells Involves Smad7-dependent Activation of p38 by TGF-β-activated Kinase 1 and Mitogen-activated Protein Kinase Kinase 3". Mol. Biol. Cell (United States) 14 (2): 529–44. doi:10.1091/mbc.02-03-0037. ISSN 1059-1524. PMC 149990. PMID 12589052. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=149990. 
12. ^ Yanagisawa, M; Nakashima K, Takeda K, Ochiai W, Takizawa T, Ueno M, Takizawa M, Shibuya H, Taga T (Dec. 2001). "Inhibition of BMP2-induced, TAK1 kinase-mediated neurite outgrowth by Smad6 and Smad7". Genes Cells (England) 6 (12): 1091–9. doi:10.1046/j.1365-2443.2001.00483.x. ISSN 1356-9597. PMID 11737269. 
13. ^ Lee, Yeon Sook; Han Jung Min, Son Sung Hwa, Choi Jin Woo, Jeon Eun Ju, Bae Suk-Chul, Park Young In, Kim Sunghoon (Jul. 2008). "AIMP1/p43 downregulates TGF-beta signaling via stabilization of smurf2". Biochem. Biophys. Res. Commun. (United States) 371 (3): 395–400. doi:10.1016/j.bbrc.2008.04.099. PMID 18448069. 
14. ^ Imoto, Seiyu; Sugiyama Kenji, Muromoto Ryuta, Sato Noriko, Yamamoto Tetsuya, Matsuda Tadashi (Sep. 2003). "Regulation of transforming growth factor-beta signaling by protein inhibitor of activated STAT, PIASy through Smad3". J. Biol. Chem. (United States) 278 (36): 34253–8. doi:10.1074/jbc.M304961200. ISSN 0021-9258. PMID 12815042. 
15. ^ Grönroos, Eva; Hellman Ulf, Heldin Carl-Henrik, Ericsson Johan (Sep. 2002). "Control of Smad7 stability by competition between acetylation and ubiquitination". Mol. Cell (United States) 10 (3): 483–93. doi:10.1016/S1097-2765(02)00639-1. ISSN 1097-2765. PMID 12408818. 
16. ^ Lebrun, J J; Takabe K, Chen Y, Vale W (Jan. 1999). "Roles of pathway-specific and inhibitory Smads in activin receptor signaling". Mol. Endocrinol. (UNITED STATES) 13 (1): 15–23. doi:10.1210/me.13.1.15. ISSN 0888-8809. PMID 9892009. 

Further reading

• Massagué J (1998). "TGF-beta signal transduction". Annu. Rev. Biochem. 67: 753–91. doi:10.1146/annurev.biochem.67.1.753. PMID 9759503. 
• Verschueren K, Huylebroeck D (2000). "Remarkable versatility of Smad proteins in the nucleus of transforming growth factor-beta activated cells". Cytokine Growth Factor Rev. 10 (3–4): 187–99. doi:10.1016/S1359-6101(99)00012-X. PMID 10647776. 
• Wrana JL, Attisano L (2000). "The Smad pathway". Cytokine Growth Factor Rev. 11 (1–2): 5–13. doi:10.1016/S1359-6101(99)00024-6. PMID 10708948. 
• Miyazono K (2000). "TGF-beta signaling by Smad proteins". Cytokine Growth Factor Rev. 11 (1–2): 15–22. doi:10.1016/S1359-6101(99)00025-8. PMID 10708949. 
• Hayashi H, Abdollah S, Qiu Y, et al. (1997). "The MAD-related protein Smad7 associates with the TGFbeta receptor and functions as an antagonist of TGFbeta signaling". Cell 89 (7): 1165–73. doi:10.1016/S0092-8674(00)80303-7. PMID 9215638. 
• Topper JN, Cai J, Qiu Y, et al. (1997). "Vascular MADs: Two novel MAD-related genes selectively inducible by flow in human vascular endothelium". Proc. Natl. Acad. Sci. U.S.A. 94 (17): 9314–9. doi:10.1073/pnas.94.17.9314. PMC 23174. PMID 9256479. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=23174. 
• Nakao A, Afrakhte M, Morén A, et al. (1997). "Identification of Smad7, a TGFbeta-inducible antagonist of TGF-beta signalling". Nature 389 (6651): 631–5. doi:10.1038/39369. PMID 9335507. 
• Röijer E, Morén A, ten Dijke P, Stenman G (1998). "Assignment1 of the Smad7 gene (MADH7) to human chromosome 18q21.1 by fluorescence in situ hybridization". Cytogenet. Cell Genet. 81 (3–4): 189–90. doi:10.1159/000015026. PMID 9730599. 
• Itóh S, Landström M, Hermansson A, et al. (1998). "Transforming growth factor beta1 induces nuclear export of inhibitory Smad7". J. Biol. Chem. 273 (44): 29195–201. doi:10.1074/jbc.273.44.29195. PMID 9786930. 
• Datta PK, Moses HL (2000). "STRAP and Smad7 Synergize in the Inhibition of Transforming Growth Factor β Signaling". Mol. Cell. Biol. 20 (9): 3157–67. doi:10.1128/MCB.20.9.3157-3167.2000. PMC 85610. PMID 10757800. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=85610. 
• Denissova NG, Pouponnot C, Long J, et al. (2000). "Transforming growth factor β-inducible independent binding of SMAD to the Smad7 promoter". Proc. Natl. Acad. Sci. U.S.A. 97 (12): 6397–402. doi:10.1073/pnas.090099297. PMC 18614. PMID 10823886. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=18614. 
• Stopa M, Anhuf D, Terstegen L, et al. (2000). "Participation of Smad2, Smad3, and Smad4 in transforming growth factor beta (TGF-beta)-induced activation of Smad7. THE TGF-beta response element of the promoter requires functional Smad binding element and E-box sequences for transcriptional regulation". J. Biol. Chem. 275 (38): 29308–17. doi:10.1074/jbc.M003282200. PMID 10887185. 
• Kavsak P, Rasmussen RK, Causing CG, et al. (2001). "Smad7 binds to Smurf2 to form an E3 ubiquitin ligase that targets the TGF beta receptor for degradation". Mol. Cell 6 (6): 1365–75. doi:10.1016/S1097-2765(00)00134-9. PMID 11163210. 
• Ebisawa T, Fukuchi M, Murakami G, et al. (2001). "Smurf1 interacts with transforming growth factor-beta type I receptor through Smad7 and induces receptor degradation". J. Biol. Chem. 276 (16): 12477–80. doi:10.1074/jbc.C100008200. PMID 11278251. 
• Itoh F, Asao H, Sugamura K, et al. (2001). "Promoting bone morphogenetic protein signaling through negative regulation of inhibitory Smads". EMBO J. 20 (15): 4132–42. doi:10.1093/emboj/20.15.4132. PMC 149146. PMID 11483516. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=149146. 
• Yanagisawa M, Nakashima K, Takeda K, et al. (2002). "Inhibition of BMP2-induced, TAK1 kinase-mediated neurite outgrowth by Smad6 and Smad7". Genes Cells 6 (12): 1091–9. doi:10.1046/j.1365-2443.2001.00483.x. PMID 11737269.