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SMAD2
Available structures PDB Ortholog search: PDBe RCSB List of PDB id codes 1DEV, 1KHX, 1U7V, 2LB3
Identifiers
Aliases	SMAD2, JV18, JV18-1, MADH2, MADR2, hMAD-2, hSMAD family member 2, LDS6, CHTD8
External IDs	OMIM: 601366; MGI: 108051; HomoloGene: 21197; GeneCards: SMAD2; OMA:SMAD2 - orthologs
Gene location (Human) Chr. Chromosome 18 (human) Band 18q21.1 Start 47,808,957 bp End 47,931,146 bp
Gene location (Mouse) Chr. Chromosome 18 (mouse) Band 18 E3|18 51.42 cM Start 76,374,651 bp End 76,444,034 bp
RNA expression pattern Bgee Human Mouse (ortholog) Top expressed in Achilles tendon sperm secondary oocyte germinal epithelium monocyte islet of Langerhans amniotic fluid tendon of biceps brachii hair follicle epithelium of colon Top expressed in saccule otic placode zygote genital tubercle otic vesicle tail of embryo lumbar spinal ganglion transitional epithelium of urinary bladder secondary oocyte primary oocyte More reference expression data BioGPS More reference expression data
Gene ontology Molecular function phosphatase binding I-SMAD binding DNA-binding transcription factor activity DNA-binding transcription activator activity, RNA polymerase II-specific R-SMAD binding co-SMAD binding transcription factor binding metal ion binding RNA polymerase II cis-regulatory region sequence-specific DNA binding transforming growth factor beta receptor binding type I transforming growth factor beta receptor binding protein homodimerization activity chromatin binding protein binding double-stranded DNA binding SMAD binding DNA binding protein heterodimerization activity ubiquitin protein ligase binding primary miRNA binding disordered domain specific binding DNA-binding transcription factor activity, RNA polymerase II-specific tau protein binding Cellular component cytoplasm cytosol nucleus heteromeric SMAD protein complex SMAD protein complex transcription regulator complex intracellular anatomical structure nucleoplasm activin responsive factor complex protein-containing complex Biological process pattern specification process ureteric bud development endoderm development response to cholesterol organ growth embryonic pattern specification zygotic specification of dorsal/ventral axis post-embryonic development protein phosphorylation pericardium development regulation of binding transforming growth factor beta receptor signaling pathway negative regulation of cell population proliferation cell fate commitment common-partner SMAD protein phosphorylation regulation of transcription, DNA-templated SMAD protein signal transduction lung development signal transduction involved in regulation of gene expression insulin secretion in utero embryonic development negative regulation of transforming growth factor beta receptor signaling pathway negative regulation of gene expression nodal signaling pathway positive regulation of transcription, DNA-templated heart development pancreas development endoderm formation activin receptor signaling pathway SMAD protein complex assembly positive regulation of nodal signaling pathway involved in determination of lateral mesoderm left/right asymmetry embryonic foregut morphogenesis negative regulation of transcription by RNA polymerase II response to glucose positive regulation of epithelial to mesenchymal transition developmental growth gastrulation primary miRNA processing positive regulation of BMP signaling pathway embryonic cranial skeleton morphogenesis negative regulation of transcription, DNA-templated paraxial mesoderm morphogenesis intracellular signal transduction somatic stem cell population maintenance mesoderm formation regulation of transforming growth factor beta receptor signaling pathway positive regulation of gene expression anterior/posterior pattern specification positive regulation of transcription by RNA polymerase II transcription, DNA-templated transcription by RNA polymerase II protein deubiquitination wound healing adrenal gland development secondary palate development Sources:Amigo / QuickGO
Orthologs Species Human Mouse Entrez 4087 17126 Ensembl ENSG00000175387 ENSMUSG00000024563 UniProt Q15796 Q62432 RefSeq (mRNA) NM_001003652 NM_001135937 NM_005901 NM_001252481 NM_010754 NM_001311070 RefSeq (protein) NP_001003652 NP_001129409 NP_005892 NP_001239410 NP_001297999 NP_034884 Location (UCSC) Chr 18: 47.81 – 47.93 Mb Chr 18: 76.37 – 76.44 Mb PubMed search
Wikidata
View/Edit Human View/Edit Mouse

Mothers against decapentaplegic homolog 2, also known as SMAD family member 2 or SMAD2, is a protein that in humans is encoded by the SMAD2 gene. MAD homolog 2 belongs to the SMAD, a family of proteins similar to the gene products of the Drosophila gene 'mothers against decapentaplegic' (Mad) and the C. elegans gene Sma. SMAD proteins are signal transducers and transcriptional modulators that mediate multiple signaling pathways.

Function

SMAD2 mediates the signal of the transforming growth factor (TGF)-beta, and thus regulates multiple cellular processes, such as cell proliferation, apoptosis, and differentiation. This protein is recruited to the TGF-beta receptors through its interaction with the SMAD anchor for receptor activation (SARA) protein. In response to TGF-beta signal, this protein is phosphorylated by the TGF-beta receptors. The phosphorylation induces the dissociation of this protein with SARA and the association with the family member SMAD4. The association with SMAD4 is important for the translocation of this protein into the cell nucleus, where it binds to target promoters and forms a transcription repressor complex with other cofactors. This protein can also be phosphorylated by activin type 1 receptor kinase, and mediates the signal from the activin. Alternatively spliced transcript variants encoding the same protein have been observed.

Like other SMADs, SMAD2 plays a role in the transmission of extracellular signals from ligands of the Transforming Growth Factor beta (TGFβ) superfamily of growth factors into the cell nucleus. Binding of a subgroup of TGFβ superfamily ligands to extracellular receptors triggers phosphorylation of SMAD2 at a Serine-Serine-Methionine-Serine (SSMS) motif at its extreme C-terminus. Phosphorylated SMAD2 is then able to form a complex with SMAD4. These complexes accumulate in the cell nucleus, where they are directly participating in the regulation of gene expression.

Nomenclature

The SMAD proteins are homologs of both the drosophila protein, mothers against decapentaplegic (MAD), and the C. elegans protein SMA. The name is a combination of the two. During Drosophila research, it was found that a mutation in the gene MAD in the mother repressed the gene decapentaplegic in the embryo. The phrase "Mothers against" was added, since mothers often form organizations opposing various issues, e.g., Mothers Against Drunk Driving, or (MADD). The nomenclature for this protein is based on a tradition of such unusual naming within the gene research community.

Interactions

Mothers against decapentaplegic homolog 2 has been shown to interact with:

• ANAPC10,
• DAB2,
• EP300,
• FOXH1,
• HDAC1,
• TGIF1,
• Insulin receptor,
• LEF1,
• Myc,
• MEF2A,
• PIAS3,
• PIN1,
• SKI protein,
• SKIL,
• SMAD3,
• SMURF2,
• SNW1,
• STRAP
• WWTR1

References

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Further reading

• Wrana JL (1998). "TGF-beta receptors and signalling mechanisms". Mineral and Electrolyte Metabolism. 24 (2–3): 120–30. doi:10.1159/000057359. PMID 9525694. S2CID 84458561.
• 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.
• Zannis VI, Kan HY, Kritis A, Zanni E, Kardassis D (March 2001). "Transcriptional regulation of the human apolipoprotein genes". Front. Biosci. 6: D456–504. doi:10.2741/Zannis. PMID 11229886.

This article incorporates text from the United States National Library of Medicine, which is in the public domain.

• Genes on human chromosome 18
• Developmental genes and proteins
• MH1 domain
• MH2 domain
• R-SMAD
• Transcription factors
• Human proteins