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Identification
HMDB Protein ID HMDBP14499
Secondary Accession Numbers None
Name Mothers against decapentaplegic homolog 7
Synonyms
  1. MAD homolog 7
  2. Mothers against DPP homolog 7
  3. Mothers against decapentaplegic homolog 8
  4. SMAD family member 7
  5. MAD homolog 8
  6. Mothers against DPP homolog 8
  7. SMAD 7
  8. Smad7
  9. hSMAD7
Gene Name SMAD7
Protein Type Unknown
Biological Properties
General Function Not Available
Specific 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.
Pathways
  • Hippo signaling pathway
  • TGF-beta signaling pathway
Reactions Not Available
GO Classification
Biological Process
regulation of ventricular cardiac muscle cell membrane depolarization
cellular response to leukemia inhibitory factor
negative regulation of sequence-specific DNA binding transcription factor activity
ventricular septum morphogenesis
protein deubiquitination
response to laminar fluid shear stress
negative regulation of protein ubiquitination
positive regulation of proteasomal ubiquitin-dependent protein catabolic process
positive regulation of protein ubiquitination
SMAD protein signal transduction
protein stabilization
BMP signaling pathway
positive regulation of cell-cell adhesion
anatomical structure morphogenesis
regulation of epithelial to mesenchymal transition
adherens junction assembly
negative regulation of T-helper 17 cell differentiation
cellular protein-containing complex localization
negative regulation of chondrocyte proliferation
negative regulation of T cell cytokine production
negative regulation of T-helper 17 type immune response
negative regulation of transcription by competitive promoter binding
negative regulation of ubiquitin-protein transferase activity
positive regulation of chondrocyte hypertrophy
regulation of activin receptor signaling pathway
artery morphogenesis
negative regulation of BMP signaling pathway
ventricular cardiac muscle tissue morphogenesis
negative regulation of transcription from RNA polymerase II promoter
positive regulation of transcription from RNA polymerase II promoter
negative regulation of peptidyl-threonine phosphorylation
cell differentiation
negative regulation of cell migration
negative regulation of ossification
negative regulation of transforming growth factor beta receptor signaling pathway
regulation of transforming growth factor beta receptor signaling pathway
regulation of cardiac muscle contraction
transforming growth factor beta receptor signaling pathway
negative regulation of epithelial to mesenchymal transition
cellular response to transforming growth factor beta stimulus
pathway-restricted SMAD protein phosphorylation
ureteric bud development
negative regulation of peptidyl-serine phosphorylation
negative regulation of pathway-restricted SMAD protein phosphorylation
Cellular Component
cytosol
centrosome
protein-containing complex
cytoplasm
plasma membrane
nucleus
nucleoplasm
fibrillar center
chromatin
heteromeric SMAD protein complex
Molecular Function
metal ion binding
collagen binding
activin binding
ubiquitin protein ligase binding
transcription regulator inhibitor activity
I-SMAD binding
beta-catenin binding
DNA binding
type I transforming growth factor beta receptor binding
Cellular Location Not Available
Gene Properties
Chromosome Location Not Available
Locus Not Available
SNPs Not Available
Gene Sequence Not Available
Protein Properties
Number of Residues 426
Molecular Weight 46425.395
Theoretical pI 8.262
Pfam Domain Function
Signals Not Available
Transmembrane Regions Not Available
Protein Sequence Not Available
GenBank ID Protein Not Available
UniProtKB/Swiss-Prot ID O15105
UniProtKB/Swiss-Prot Entry Name SMAD7_HUMAN
PDB IDs
GenBank Gene ID Not Available
GeneCard ID Not Available
GenAtlas ID Not Available
HGNC ID Not Available
References
General References
  1. Ota T, Suzuki Y, Nishikawa T, Otsuki T, Sugiyama T, Irie R, Wakamatsu A, Hayashi K, Sato H, Nagai K, Kimura K, Makita H, Sekine M, Obayashi M, Nishi T, Shibahara T, Tanaka T, Ishii S, Yamamoto J, Saito K, Kawai Y, Isono Y, Nakamura Y, Nagahari K, Murakami K, Yasuda T, Iwayanagi T, Wagatsuma M, Shiratori A, Sudo H, Hosoiri T, Kaku Y, Kodaira H, Kondo H, Sugawara M, Takahashi M, Kanda K, Yokoi T, Furuya T, Kikkawa E, Omura Y, Abe K, Kamihara K, Katsuta N, Sato K, Tanikawa M, Yamazaki M, Ninomiya K, Ishibashi T, Yamashita H, Murakawa K, Fujimori K, Tanai H, Kimata M, Watanabe M, Hiraoka S, Chiba Y, Ishida S, Ono Y, Takiguchi S, Watanabe S, Yosida M, Hotuta T, Kusano J, Kanehori K, Takahashi-Fujii A, Hara H, Tanase TO, Nomura Y, Togiya S, Komai F, Hara R, Takeuchi K, Arita M, Imose N, Musashino K, Yuuki H, Oshima A, Sasaki N, Aotsuka S, Yoshikawa Y, Matsunawa H, Ichihara T, Shiohata N, Sano S, Moriya S, Momiyama H, Satoh N, Takami S, Terashima Y, Suzuki O, Nakagawa S, Senoh A, Mizoguchi H, Goto Y, Shimizu F, Wakebe H, Hishigaki H, Watanabe T, Sugiyama A, Takemoto M, Kawakami B, Yamazaki M, Watanabe K, Kumagai A, Itakura S, Fukuzumi Y, Fujimori Y, Komiyama M, Tashiro H, Tanigami A, Fujiwara T, Ono T, Yamada K, Fujii Y, Ozaki K, Hirao M, Ohmori Y, Kawabata A, Hikiji T, Kobatake N, Inagaki H, Ikema Y, Okamoto S, Okitani R, Kawakami T, Noguchi S, Itoh T, Shigeta K, Senba T, Matsumura K, Nakajima Y, Mizuno T, Morinaga M, Sasaki M, Togashi T, Oyama M, Hata H, Watanabe M, Komatsu T, Mizushima-Sugano J, Satoh T, Shirai Y, Takahashi Y, Nakagawa K, Okumura K, Nagase T, Nomura N, Kikuchi H, Masuho Y, Yamashita R, Nakai K, Yada T, Nakamura Y, Ohara O, Isogai T, Sugano S: Complete sequencing and characterization of 21,243 full-length human cDNAs. Nat Genet. 2004 Jan;36(1):40-5. Epub 2003 Dec 21. [PubMed:14702039 ]
  2. Gerhard DS, Wagner L, Feingold EA, Shenmen CM, Grouse LH, Schuler G, Klein SL, Old S, Rasooly R, Good P, Guyer M, Peck AM, Derge JG, Lipman D, Collins FS, Jang W, Sherry S, Feolo M, Misquitta L, Lee E, Rotmistrovsky K, Greenhut SF, Schaefer CF, Buetow K, Bonner TI, Haussler D, Kent J, Kiekhaus M, Furey T, Brent M, Prange C, Schreiber K, Shapiro N, Bhat NK, Hopkins RF, Hsie F, Driscoll T, Soares MB, Casavant TL, Scheetz TE, Brown-stein MJ, Usdin TB, Toshiyuki S, Carninci P, Piao Y, Dudekula DB, Ko MS, Kawakami K, Suzuki Y, Sugano S, Gruber CE, Smith MR, Simmons B, Moore T, Waterman R, Johnson SL, Ruan Y, Wei CL, Mathavan S, Gunaratne PH, Wu J, Garcia AM, Hulyk SW, Fuh E, Yuan Y, Sneed A, Kowis C, Hodgson A, Muzny DM, McPherson J, Gibbs RA, Fahey J, Helton E, Ketteman M, Madan A, Rodrigues S, Sanchez A, Whiting M, Madari A, Young AC, Wetherby KD, Granite SJ, Kwong PN, Brinkley CP, Pearson RL, Bouffard GG, Blakesly RW, Green ED, Dickson MC, Rodriguez AC, Grimwood J, Schmutz J, Myers RM, Butterfield YS, Griffith M, Griffith OL, Krzywinski MI, Liao N, Morin R, Palmquist D, Petrescu AS, Skalska U, Smailus DE, Stott JM, Schnerch A, Schein JE, Jones SJ, Holt RA, Baross A, Marra MA, Clifton S, Makowski KA, Bosak S, Malek J: The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC). Genome Res. 2004 Oct;14(10B):2121-7. [PubMed:15489334 ]
  3. Nusbaum C, Zody MC, Borowsky ML, Kamal M, Kodira CD, Taylor TD, Whittaker CA, Chang JL, Cuomo CA, Dewar K, FitzGerald MG, Yang X, Abouelleil A, Allen NR, Anderson S, Bloom T, Bugalter B, Butler J, Cook A, DeCaprio D, Engels R, Garber M, Gnirke A, Hafez N, Hall JL, Norman CH, Itoh T, Jaffe DB, Kuroki Y, Lehoczky J, Lui A, Macdonald P, Mauceli E, Mikkelsen TS, Naylor JW, Nicol R, Nguyen C, Noguchi H, O'Leary SB, O'Neill K, Piqani B, Smith CL, Talamas JA, Topham K, Totoki Y, Toyoda A, Wain HM, Young SK, Zeng Q, Zimmer AR, Fujiyama A, Hattori M, Birren BW, Sakaki Y, Lander ES: DNA sequence and analysis of human chromosome 18. Nature. 2005 Sep 22;437(7058):551-5. [PubMed:16177791 ]
  4. Massague J: TGF-beta signal transduction. Annu Rev Biochem. 1998;67:753-91. [PubMed:9759503 ]
  5. Verschueren K, Huylebroeck D: Remarkable versatility of Smad proteins in the nucleus of transforming growth factor-beta activated cells. Cytokine Growth Factor Rev. 1999 Sep-Dec;10(3-4):187-99. [PubMed:10647776 ]
  6. Wrana JL, Attisano L: The Smad pathway. Cytokine Growth Factor Rev. 2000 Mar-Jun;11(1-2):5-13. [PubMed:10708948 ]
  7. Miyazono K: TGF-beta signaling by Smad proteins. Cytokine Growth Factor Rev. 2000 Mar-Jun;11(1-2):15-22. [PubMed:10708949 ]
  8. Itoh F, Asao H, Sugamura K, Heldin CH, ten Dijke P, Itoh S: Promoting bone morphogenetic protein signaling through negative regulation of inhibitory Smads. EMBO J. 2001 Aug 1;20(15):4132-42. [PubMed:11483516 ]
  9. Koinuma D, Shinozaki M, Komuro A, Goto K, Saitoh M, Hanyu A, Ebina M, Nukiwa T, Miyazawa K, Imamura T, Miyazono K: Arkadia amplifies TGF-beta superfamily signalling through degradation of Smad7. EMBO J. 2003 Dec 15;22(24):6458-70. [PubMed:14657019 ]
  10. Liu W, Rui H, Wang J, Lin S, He Y, Chen M, Li Q, Ye Z, Zhang S, Chan SC, Chen YG, Han J, Lin SC: Axin is a scaffold protein in TGF-beta signaling that promotes degradation of Smad7 by Arkadia. EMBO J. 2006 Apr 19;25(8):1646-58. Epub 2006 Apr 6. [PubMed:16601693 ]
  11. Hayashi H, Abdollah S, Qiu Y, Cai J, Xu YY, Grinnell BW, Richardson MA, Topper JN, Gimbrone MA Jr, Wrana JL, Falb D: The MAD-related protein Smad7 associates with the TGFbeta receptor and functions as an antagonist of TGFbeta signaling. Cell. 1997 Jun 27;89(7):1165-73. [PubMed:9215638 ]
  12. Topper JN, Cai J, Qiu Y, Anderson KR, Xu YY, Deeds JD, Feeley R, Gimeno CJ, Woolf EA, Tayber O, Mays GG, Sampson BA, Schoen FJ, Gimbrone MA Jr, Falb D: Vascular MADs: two novel MAD-related genes selectively inducible by flow in human vascular endothelium. Proc Natl Acad Sci U S A. 1997 Aug 19;94(17):9314-9. [PubMed:9256479 ]
  13. Nakao A, Afrakhte M, Moren A, Nakayama T, Christian JL, Heuchel R, Itoh S, Kawabata M, Heldin NE, Heldin CH, ten Dijke P: Identification of Smad7, a TGFbeta-inducible antagonist of TGF-beta signalling. Nature. 1997 Oct 9;389(6651):631-5. [PubMed:9335507 ]
  14. Kavsak P, Rasmussen RK, Causing CG, Bonni S, Zhu H, Thomsen GH, Wrana JL: Smad7 binds to Smurf2 to form an E3 ubiquitin ligase that targets the TGF beta receptor for degradation. Mol Cell. 2000 Dec;6(6):1365-75. [PubMed:11163210 ]
  15. Ogunjimi AA, Briant DJ, Pece-Barbara N, Le Roy C, Di Guglielmo GM, Kavsak P, Rasmussen RK, Seet BT, Sicheri F, Wrana JL: Regulation of Smurf2 ubiquitin ligase activity by anchoring the E2 to the HECT domain. Mol Cell. 2005 Aug 5;19(3):297-308. [PubMed:16061177 ]
  16. Chong PA, Lin H, Wrana JL, Forman-Kay JD: An expanded WW domain recognition motif revealed by the interaction between Smad7 and the E3 ubiquitin ligase Smurf2. J Biol Chem. 2006 Jun 23;281(25):17069-75. Epub 2006 Apr 26. [PubMed:16641086 ]
  17. Shi W, Sun C, He B, Xiong W, Shi X, Yao D, Cao X: GADD34-PP1c recruited by Smad7 dephosphorylates TGFbeta type I receptor. J Cell Biol. 2004 Jan 19;164(2):291-300. doi: 10.1083/jcb.200307151. Epub 2004 Jan 12. [PubMed:14718519 ]
  18. Lebrun JJ, Takabe K, Chen Y, Vale W: Roles of pathway-specific and inhibitory Smads in activin receptor signaling. Mol Endocrinol. 1999 Jan;13(1):15-23. doi: 10.1210/mend.13.1.0218. [PubMed:9892009 ]
  19. Ebisawa T, Fukuchi M, Murakami G, Chiba T, Tanaka K, Imamura T, Miyazono K: Smurf1 interacts with transforming growth factor-beta type I receptor through Smad7 and induces receptor degradation. J Biol Chem. 2001 Apr 20;276(16):12477-80. doi: 10.1074/jbc.C100008200. Epub 2001 Feb 13. [PubMed:11278251 ]
  20. Liu X, Nagarajan RP, Vale W, Chen Y: Phosphorylation regulation of the interaction between Smad7 and activin type I receptor. FEBS Lett. 2002 May 22;519(1-3):93-8. doi: 10.1016/s0014-5793(02)02718-7. [PubMed:12023024 ]
  21. Gronroos E, Hellman U, Heldin CH, Ericsson J: Control of Smad7 stability by competition between acetylation and ubiquitination. Mol Cell. 2002 Sep;10(3):483-93. doi: 10.1016/s1097-2765(02)00639-1. [PubMed:12408818 ]
  22. Seong HA, Jung H, Kim KT, Ha H: 3-Phosphoinositide-dependent PDK1 negatively regulates transforming growth factor-beta-induced signaling in a kinase-dependent manner through physical interaction with Smad proteins. J Biol Chem. 2007 Apr 20;282(16):12272-89. doi: 10.1074/jbc.M609279200. Epub 2007 Feb 27. [PubMed:17327236 ]
  23. Broderick P, Carvajal-Carmona L, Pittman AM, Webb E, Howarth K, Rowan A, Lubbe S, Spain S, Sullivan K, Fielding S, Jaeger E, Vijayakrishnan J, Kemp Z, Gorman M, Chandler I, Papaemmanuil E, Penegar S, Wood W, Sellick G, Qureshi M, Teixeira A, Domingo E, Barclay E, Martin L, Sieber O, Kerr D, Gray R, Peto J, Cazier JB, Tomlinson I, Houlston RS: A genome-wide association study shows that common alleles of SMAD7 influence colorectal cancer risk. Nat Genet. 2007 Nov;39(11):1315-7. doi: 10.1038/ng.2007.18. Epub 2007 Oct 14. [PubMed:17934461 ]