cd10530

SET domain found in SET domain-containing protein 7 (SETD7) and similar proteins

CDD entry
Member databaseCDD
CDD typedomain
Short nameSET_SETD7
SetSET

Description

SETD7 (EC 2.1.1.43; also termed histone H3-K4 methyltransferase SETD7, H3-K4-HMTase SETD7, lysine N-methyltransferase 7 (KMT7) or SET7/9) is a histone-lysine N-methyltransferase that specifically monomethylates 'Lys-4' of histone H3. It plays a central role in the transcriptional activation of genes such as collagenase or insulin. Set7/9 also methylates non-histone proteins, including estrogen receptor alpha (ERa), suggesting it has a role in diverse biological processes. ERa methylation by Set7/9 stabilizes ERa and activates its transcriptional activities, which are involved in the carcinogenesis of breast cancer. In a high-throughput screen, treatment of human breast cancer cells (MCF7 cells) with cyproheptadine, a Set7/9 inhibitor, decreased the expression and transcriptional activity of ERa, thereby inhibiting estrogen-dependent cell growth.
[9, 3, 7, 5, 1, 4, 11, 8, 6, 14, 2, 12, 13, 10]

References

1.(R)-PFI-2 is a potent and selective inhibitor of SETD7 methyltransferase activity in cells. Barsyte-Lovejoy D, Li F, Oudhoff MJ, Tatlock JH, Dong A, Zeng H, Wu H, Freeman SA, Schapira M, Senisterra GA, Kuznetsova E, Marcellus R, Allali-Hassani A, Kennedy S, Lambert JP, Couzens AL, Aman A, Gingras AC, Al-Awar R, Fish PV, Gerstenberger BS, Roberts L, Benn CL, Grimley RL, Braam MJ, Rossi FM, Sudol M, Brown PJ, Bunnage ME, Owen DR, Zaph C, Vedadi M, Arrowsmith CH. Proc Natl Acad Sci U S A 111, 12853-8, (2014). PMID: 25136132

2.Crystal structure and functional analysis of the histone methyltransferase SET7/9. Wilson JR, Jing C, Walker PA, Martin SR, Howell SA, Blackburn GM, Gamblin SJ, Xiao B. Cell 111, 105-15, (2002). View articlePMID: 12372304

3.Identification of Cyproheptadine as an Inhibitor of SET Domain Containing Lysine Methyltransferase 7/9 (Set7/9) That Regulates Estrogen-Dependent Transcription. Takemoto Y, Ito A, Niwa H, Okamura M, Fujiwara T, Hirano T, Handa N, Umehara T, Sonoda T, Ogawa K, Tariq M, Nishino N, Dan S, Kagechika H, Yamori T, Yokoyama S, Yoshida M. J Med Chem 59, 3650-60, (2016). PMID: 27088648

4.Regulation of estrogen receptor alpha by the SET7 lysine methyltransferase. Subramanian K, Jia D, Kapoor-Vazirani P, Powell DR, Collins RE, Sharma D, Peng J, Cheng X, Vertino PM. Mol. Cell 30, 336-47, (2008). View articlePMID: 18471979

5.Sulfur-Oxygen Chalcogen Bonding Mediates AdoMet Recognition in the Lysine Methyltransferase SET7/9. Fick RJ, Kroner GM, Nepal B, Magnani R, Horowitz S, Houtz RL, Scheiner S, Trievel RC. ACS Chem Biol 11, 748-54, (2016). PMID: 26713889

6.Structures of histone methyltransferase SET7/9 in complexes with adenosylmethionine derivatives. Niwa H, Handa N, Tomabechi Y, Honda K, Toyama M, Ohsawa N, Shirouzu M, Kagechika H, Hirano T, Umehara T, Yokoyama S. Acta Crystallogr D Biol Crystallogr 69, 595-602, (2013). PMID: 23519668

7.Proper Activity of Histone H3 Lysine 4 (H3K4) Methyltransferase Is Required for Morphogenesis during Zebrafish Cardiogenesis. Kim JD, Kim E, Koun S, Ham HJ, Rhee M, Kim MJ, Huh TL. Mol Cells 38, 580-6, (2015). PMID: 25997738

8.SET7/9 catalytic mutants reveal the role of active site water molecules in lysine multiple methylation. Del Rizzo PA, Couture JF, Dirk LM, Strunk BS, Roiko MS, Brunzelle JS, Houtz RL, Trievel RC. J. Biol. Chem. 285, 31849-58, (2010). View articlePMID: 20675860

9.Purification and functional characterization of a histone H3-lysine 4-specific methyltransferase. Wang H, Cao R, Xia L, Erdjument-Bromage H, Borchers C, Tempst P, Zhang Y. Mol Cell 8, 1207-17, (2001). PMID: 11779497

10.Regulation of p53 activity through lysine methylation. Chuikov S, Kurash JK, Wilson JR, Xiao B, Justin N, Ivanov GS, McKinney K, Tempst P, Prives C, Gamblin SJ, Barlev NA, Reinberg D. Nature 432, 353-60, (2004). View articlePMID: 15525938

11.Set9, a novel histone H3 methyltransferase that facilitates transcription by precluding histone tail modifications required for heterochromatin formation. Nishioka K, Chuikov S, Sarma K, Erdjument-Bromage H, Allis CD, Tempst P, Reinberg D. Genes Dev 16, 479-89, (2002). PMID: 11850410

12.The active site of the SET domain is constructed on a knot. Jacobs SA, Harp JM, Devarakonda S, Kim Y, Rastinejad F, Khorasanizadeh S. Nat. Struct. Biol. 9, 833-8, (2002). PMID: 12389038

13.Mechanism of histone lysine methyl transfer revealed by the structure of SET7/9-AdoMet. Kwon T, Chang JH, Kwak E, Lee CW, Joachimiak A, Kim YC, Lee J, Cho Y. EMBO J. 22, 292-303, (2003). View articlePMID: 12514135

14.Catalytic mechanism and product specificity of the histone lysine methyltransferase SET7/9: an ab initio QM/MM-FE study with multiple initial structures. Hu P, Zhang Y. J Am Chem Soc 128, 1272-8, (2006). PMID: 16433545

Integrated to
External Links
This website requires cookies, and the limited processing of your personal data in order to function. By using the site you are agreeing to this as outlined in our Privacy Notice and Terms of Use.