Mothers against decapentaplegic homolog 6

SMAD family member 6
Identifiers
Symbols	SMAD6; HsT17432; MADH6; MADH7
External IDs	OMIM: 602931 MGI: 1336883 HomoloGene: 4079 GeneCards: SMAD6 Gene
Gene Ontology Molecular function • sequence-specific DNA binding transcription factor activity • protein binding • transforming growth factor beta receptor, inhibitory cytoplasmic mediator activity • transforming growth factor beta receptor, inhibitory cytoplasmic mediator activity • ubiquitin protein ligase binding • type I transforming growth factor beta receptor binding • co-SMAD binding • I-SMAD binding • R-SMAD binding • type I activin receptor binding Cellular component • intracellular • nucleus • transcription factor complex • cytoplasm • cytosol • cytosol Biological process • ureteric bud development • immune response • transforming growth factor beta receptor signaling pathway • zygotic specification of dorsal/ventral axis • negative regulation of SMAD protein complex assembly • BMP signaling pathway • negative regulation of transforming growth factor beta receptor signaling pathway • negative regulation of BMP signaling pathway • response to laminar fluid shear stress • negative regulation of apoptosis • negative regulation of caspase activity • positive regulation of S phase of mitotic cell cycle • negative regulation of pathway-restricted SMAD protein phosphorylation • negative regulation of pathway-restricted SMAD protein phosphorylation Sources: Amigo / QuickGO
RNA expression pattern
More reference expression data
Orthologs
Species	Human	Mouse
Entrez	4091	17130
Ensembl	ENSG00000137834	ENSMUSG00000036867
UniProt	O43541	n/a
RefSeq (mRNA)	NM_001142861.2	NM_008542.3
RefSeq (protein)	NP_001136333.1	NP_032568.3
Location (UCSC)	Chr 15: 66.99 – 67.07 Mb	Chr 9: 63.8 – 63.87 Mb
PubMed search	[1]	[2]

SMAD family member 6, also known as SMAD6, is a protein that in humans is encoded by the SMAD6 gene.^[1]

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).

Interactions

Mothers against decapentaplegic homolog 6 has been shown to interact with HOXC8,^[2] Mothers against decapentaplegic homolog 7,^[3] PIAS4,^[4] STRAP^[5] and MAP3K7.^[6][7]

References

1. ^ "Entrez Gene: SMAD6 SMAD family member 6". http://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=4091. 
2. ^ Bai, S; Shi X, Yang X, Cao X (Mar. 2000). "Smad6 as a transcriptional corepressor". J. Biol. Chem. (UNITED STATES) 275 (12): 8267–70. doi:10.1074/jbc.275.12.8267. ISSN 0021-9258. PMID 10722652. 
3. ^ 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. 
4. ^ 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. 
5. ^ 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. 
6. ^ Kimura, N; Matsuo R, Shibuya H, Nakashima K, Taga T (Jun. 2000). "BMP2-induced apoptosis is mediated by activation of the TAK1-p38 kinase pathway that is negatively regulated by Smad6". J. Biol. Chem. (UNITED STATES) 275 (23): 17647–52. doi:10.1074/jbc.M908622199. ISSN 0021-9258. PMID 10748100. 
7. ^ 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. 

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 et al. (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 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. 
• 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. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=316444. 
• Afrakhte M, Morén A, Jossan S et al. (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 et al. (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 et al. (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. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=85610. 
• 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. 
• Schiffer M, Schiffer LE, Gupta A et al. (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.