Mothers against decapentaplegic homolog 6

SMAD6
Identifiers
Aliases	SMAD6, AOVD2, HsT17432, MADH6, MADH7, SMAD family member 6
External IDs	OMIM: 602931 MGI: 1336883 HomoloGene: 4079 GeneCards: SMAD6
Gene ontology Molecular function • DNA binding • R-SMAD binding • type I transforming growth factor beta receptor binding • co-SMAD binding • I-SMAD binding • transforming growth factor beta receptor, inhibitory cytoplasmic mediator activity • transcription factor activity, sequence-specific DNA binding • chromatin binding • type I activin receptor binding • metal ion binding • RNA polymerase II core promoter proximal region sequence-specific DNA binding • protein binding • identical protein binding • transcription regulatory region DNA binding • ubiquitin protein ligase binding Cellular component • cytoplasm • cytosol • transcription factor complex • intracellular • protein complex • nucleus Biological process • ureteric bud development • heart valve development • regulation of transcription, DNA-templated • ventricular septum development • zygotic specification of dorsal/ventral axis • negative regulation of SMAD protein complex assembly • response to laminar fluid shear stress • negative regulation of apoptotic process • negative regulation of transforming growth factor beta receptor signaling pathway • coronary vasculature development • BMP signaling pathway • transcription, DNA-templated • negative regulation of pathway-restricted SMAD protein phosphorylation • response to estrogen • negative regulation of BMP signaling pathway • aorta development • cell-substrate adhesion • immune response • transforming growth factor beta receptor signaling pathway • fat cell differentiation • negative regulation of cell proliferation • mitral valve morphogenesis • positive regulation of pri-miRNA transcription from RNA polymerase II promoter • negative regulation of ossification • pulmonary valve morphogenesis • outflow tract septum morphogenesis Sources:Amigo / QuickGO
RNA expression pattern
More reference expression data
Orthologs
Species	Human	Mouse
Entrez	4091	17130
Ensembl	ENSG00000137834	ENSMUSG00000036867
UniProt	O43541	O35182
RefSeq (mRNA)	NM_001142861 NM_005585	NM_008542
RefSeq (protein)	NP_005576.3	NP_032568.3
Location (UCSC)	Chr 15: 66.7 – 66.78 Mb	Chr 9: 63.95 – 64.02 Mb
PubMed search	[1]	[2]
Wikidata

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SMAD family member 6, also known as SMAD6, is a protein that in humans is encoded by the SMAD6 gene.^[3]

SMAD6 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 modulators. Like many other TGFβ family members SMAD6 is involved in cell signalling. It acts as a regulator of TGFβ family (such as bone morphogenetic proteins) activity by competing with SMAD4 and preventing the transcription of SMAD4's gene products. There are two known isoforms of this protein.

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; and based on a tradition of such unusual naming within the gene research community.^[4]

Interactions

Mothers against decapentaplegic homolog 6 has been shown to interact with:

• HOXC8,^[5]
• MAP3K7,^[6][7]
• Mothers against decapentaplegic homolog 7,^[8]
• PIAS4,^[9] and
• STRAP.^[10]

References

1. "Human PubMed Reference:".
2. "Mouse PubMed Reference:".
3. "Entrez Gene: SMAD6 SMAD family member 6".
4. "Sonic Hedgehog, DICER, and the Problem With Naming Genes", Sep 26, 2014, Michael White. psmag.com
5. Bai S, Shi X, Yang X, Cao X (March 2000). "Smad6 as a transcriptional corepressor". J. Biol. Chem. 275 (12): 8267–70. doi:10.1074/jbc.275.12.8267. PMID 10722652.
6. Kimura N, Matsuo R, Shibuya H, Nakashima K, Taga T (June 2000). "BMP2-induced apoptosis is mediated by activation of the TAK1-p38 kinase pathway that is negatively regulated by Smad6". J. Biol. Chem. 275 (23): 17647–52. doi:10.1074/jbc.M908622199. PMID 10748100.
7. Yanagisawa M, Nakashima K, Takeda K, Ochiai W, Takizawa T, Ueno M, Takizawa M, Shibuya H, Taga T (December 2001). "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.
8. 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, Falb D (August 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.
9. Imoto S, Sugiyama K, Muromoto R, Sato N, Yamamoto T, Matsuda T (September 2003). "Regulation of transforming growth factor-beta signaling by protein inhibitor of activated STAT, PIASy through Smad3". J. Biol. Chem. 278 (36): 34253–8. doi:10.1074/jbc.M304961200. PMID 12815042.
10. Datta PK, Moses HL (May 2000). "STRAP and Smad7 synergize in the inhibition of transforming growth factor beta signaling". Mol. Cell. Biol. 20 (9): 3157–67. doi:10.1128/MCB.20.9.3157-3167.2000. PMC 85610. PMID 10757800.

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.
• Riggins GJ, Thiagalingam S, Rozenblum E, Weinstein CL, Kern SE, Hamilton SR, Willson JK, Markowitz SD, Kinzler KW, Vogelstein B (1996). "Mad-related genes in the human". Nat. Genet. 13 (3): 347–9. doi:10.1038/ng0796-347. PMID 8673135.
• 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, Falb D (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.
• Hata A, Lagna G, Massagué J, Hemmati-Brivanlou A (1998). "Smad6 inhibits BMP/Smad1 signaling by specifically competing with the Smad4 tumor suppressor". Genes Dev. 12 (2): 186–97. doi:10.1101/gad.12.2.186. PMC 316444. PMID 9436979.
• Afrakhte M, Morén A, Jossan S, Itoh S, Sampath K, Westermark B, Heldin CH, Heldin NE, ten Dijke P (1998). "Induction of inhibitory Smad6 and Smad7 mRNA by TGF-beta family members". Biochem. Biophys. Res. Commun. 249 (2): 505–11. doi:10.1006/bbrc.1998.9170. PMID 9712726.
• Galvin KM, Donovan MJ, Lynch CA, Meyer RI, Paul RJ, Lorenz JN, Fairchild-Huntress V, Dixon KL, Dunmore JH, Gimbrone MA, Falb D, Huszar D (2000). "A role for smad6 in development and homeostasis of the cardiovascular system". Nat. Genet. 24 (2): 171–4. doi:10.1038/72835. PMID 10655064.
• Bai S, Shi X, Yang X, Cao X (2000). "Smad6 as a transcriptional corepressor". J. Biol. Chem. 275 (12): 8267–70. doi:10.1074/jbc.275.12.8267. PMID 10722652.
• Kimura N, Matsuo R, Shibuya H, Nakashima K, Taga T (2000). "BMP2-induced apoptosis is mediated by activation of the TAK1-p38 kinase pathway that is negatively regulated by Smad6". J. Biol. Chem. 275 (23): 17647–52. doi:10.1074/jbc.M908622199. PMID 10748100.
• 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.
• Ebisawa T, Fukuchi M, Murakami G, Chiba T, Tanaka K, Imamura T, Miyazono K (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, Heldin CH, ten Dijke P, Itoh S (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.
• Yanagisawa M, Nakashima K, Takeda K, Ochiai W, Takizawa T, Ueno M, Takizawa M, Shibuya H, Taga T (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.
• Schiffer M, Schiffer LE, Gupta A, Shaw AS, Roberts IS, Mundel P, Böttinger EP (2003). "Inhibitory smads and tgf-Beta signaling in glomerular cells". J. Am. Soc. Nephrol. 13 (11): 2657–66. doi:10.1097/01.ASN.0000033276.06451.50. PMID 12397035.