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SMAD4 - SMAD family member 4

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Gene
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Interaction
Network

Canonical
Pathway

Literature

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Disease

Compound

Expression

Regulation

SNP

Entrez Gene Name: SMAD family member 4
Entrez GeneID: Human(4089), Mouse(17128), Rat(50554)
Synonyms: AW743858, D18Wsu70e, DPC4, JIP, MADH4, SMAD4, Smaug1

Gene Summary

  • Human (4089): This gene encodes a member of the Smad family of signal transduction proteins. Smad proteins are phosphorylated and activated by transmembrane serine-threonine receptor kinases in response to TGF-beta signaling. The product of this gene forms homomeric complexes and heteromeric complexes with other activated Smad proteins, which then accumulate in the nucleus and regulate the transcription of target genes. This protein binds to DNA and recognizes an 8-bp palindromic sequence (GTCTAGAC) called the Smad-binding element (SBE). The Smad proteins are subject to complex regulation by post-translational modifications. Mutations or deletions in this gene have been shown to result in pancreatic cancer, juvenile polyposis syndrome, and hereditary hemorrhagic telangiectasia syndrome. [provided by RefSeq]
  • Rat (50554): transduces signal from TGF-beta; deletion of human homolog gene is associated with pancreatic carcinomas [RGD]
Molecular Functions | Biological Process | Cellular Components | Protein Domains | Subcellular Locations | Pathways | Literature References | IPA Extras

Cell Regulation

Regulates:
  • CDKN1A
  • SERPINE1
  • CCND1
View all 216 in IPA
Regulated by:
  • TGFB1
  • Tgf beta
  • SMAD4
View all 160 in IPA
Binds:
  • SMAD3
  • SMAD2
  • SMAD1
View all 388 in IPA
Role in cell:
  • proliferation
  • growth
  • expression in
View all 36 in IPA
Disease:
  • cancer
  • tumorigenesis
  • pancreatic cancer
View all 30 in IPA

Biological Process

anterior/posterior pattern formation, BMP signaling pathway, branching involved in ureteric bud morphogenesis, cell proliferation, developmental growth, endoderm development, formation of anatomical boundary, gastrulation, gastrulation with mouth forming second, in utero embryonic development, kidney development, mesoderm development, metanephric mesenchyme morphogenesis, negative regulation of cell death, negative regulation of cell growth, negative regulation of cell proliferation, negative regulation of protein catabolic process, negative regulation of transcription, DNA-dependent, nephrogenic mesenchyme morphogenesis, neuron fate commitment, palate development, positive regulation of epithelial to mesenchymal transition, positive regulation of pathway-restricted SMAD protein phosphorylation, positive regulation of SMAD protein import into nucleus, positive regulation of transcription from RNA polymerase II promoter, positive regulation of transcription, DNA-dependent, positive regulation of transforming growth factor beta receptor signaling pathway, regulation of binding, regulation of cell proliferation, regulation of transcription from RNA polymerase II promoter, regulation of transcription, DNA-dependent, regulation of transforming growth factor beta receptor signaling pathway, regulation of transforming growth factor-beta2 production, response to hypoxia, response to transforming growth factor beta stimulus, SMAD protein complex assembly, SMAD protein signal transduction, somite rostral/caudal axis specification, tissue morphogenesis, transcription, DNA-dependent, transforming growth factor beta receptor signaling pathway

Cellular Components

activin responsive factor complex, centrosome, cytoplasm, cytosol, intracellular, nucleolus, nucleoplasm, nucleus, protein complex, transcription factor complex

Literature References

  • 16189514Rual JF, Venkatesan K, Hao T, Hirozane-Kishikawa T, Dricot A, Li N, Berriz GF, Gibbons FD, Dreze M, Ayivi-Guedehoussou N, Klitgord N, Simon C, Boxem M, Milstein S, Rosenberg J, Goldberg DS, Zhang LV, Wong SL, Franklin G, Li S, Albala JS, Lim J, Fraughton C, Llamosas E, Cevik S, Bex C, Lamesch P, Sikorski RS, Vandenhaute J, Zoghbi HY, Smolyar A, Bosak S, Sequerra R, Doucette-Stamm L, Cusick ME, Hill DE, Roth FP, Vidal M. Towards a proteome-scale map of the human protein-protein interaction network.Nature 2005 10 20;437(7062):1173-8
  • 15761153Barrios-Rodiles M, Brown KR, Ozdamar B, Bose R, Liu Z, Donovan RS, Shinjo F, Liu Y, Dembowy J, Taylor IW, Luga V, Przulj N, Robinson M, Suzuki H, Hayashizaki Y, Jurisica I, Wrana JL. High-throughput mapping of a dynamic signaling network in mammalian cells.Science 2005 03 11;307(5715):1621-5
  • 19135894Dupont S, Mamidi A, Cordenonsi M, Montagner M, Zacchigna L, Adorno M, Martello G, Stinchfield MJ, Soligo S, Morsut L, Inui M, Moro S, Modena N, Argenton F, Newfeld SJ, Piccolo S. FAM/USP9x, a deubiquitinating enzyme essential for TGFbeta signaling, controls Smad4 monoubiquitination.Cell 2009 01 9;136(1):123-35
View 3315 categorized literature findings and their references in IPA

Molecular Functions

chromatin binding, collagen binding, DNA binding, I-SMAD binding, identical protein binding, protein binding, protein homodimerization activity, R-SMAD binding, sequence-specific DNA binding, sequence-specific DNA binding transcription factor activity, SMAD binding, transcription regulatory region DNA binding, transforming growth factor beta receptor, common-partner cytoplasmic mediator activity

Pathways

Protein Domains

activation domain, chromatin binding, collagen binding, DNA binding, DNA binding domain, identical protein binding, linker domain, MH domain, MH1, MH1 domain, MH2, MH2 domain, proline rich domain, protein binding, protein homodimerization, SMAD binding, Smad4 activation domain, TGFbeta receptor, common-partner cytoplasmic mediator, transcription factor, transcription regulator

Subcellular Locations

centrosome, Cytoplasm, cytosol, filopodia, nuclear fraction, nucleoplasm, Nucleus, perinuclear region, photoreceptor inner segments, zona pellucida

IPA Extras