D
IPR044419

SMYD2, SET domain

InterPro entry
Short nameSMYD2_SET
Overlapping
homologous
superfamilies
 
domain relationships

Description

This entry represents the SET domain of SET and MYND domain-containing protein 2 (SMYD2). SMYD2 functions as a histone methyltransferase that methylates both histones and non-histone proteins, including p53/TP53 and RB1
[4, 5]
. It specifically methylates histone H3 'Lys-4' (H3K4me) and dimethylates histone H3 'Lys-36' (H3K36me2). It plays a role in myofilament organisation in both skeletal and cardiac muscles via Hsp90 methylation
[7]
. SMYD2 overexpression is associated with tumour cell proliferation and a worse outcome in human papillomavirus-unrelated nonmultiple head and neck carcinomas
[8]
. It regulates leukemia cell growth such that diminished SMYD2 expression upregulates SET7/9, thereby possibly shifting leukemia cells from growth to quiescence state associated with resistance to DNA damage associated with Acute Myeloid Leukemia (AML)
[9]
.

The SMYD family consists of five members including SMYD1/2/3/4/5. They contain two highly conserved structural and functional domains, the SET and MYND domains. The SET domain is involved in lysine methylation, while the MYND domain is involved in protein-protein interaction. They are essential in several mammalian developmental pathways
[1, 3, 2, 6]
.

References

1.SMYD proteins: key regulators in skeletal and cardiac muscle development and function. Du SJ, Tan X, Zhang J. Anat Rec (Hoboken) 297, 1650-62, (2014). PMID: 25125178

2.Novel Oxindole Sulfonamides and Sulfamides: EPZ031686, the First Orally Bioavailable Small Molecule SMYD3 Inhibitor. Mitchell LH, Boriack-Sjodin PA, Smith S, Thomenius M, Rioux N, Munchhof M, Mills JE, Klaus C, Totman J, Riera TV, Raimondi A, Jacques SL, West K, Foley M, Waters NJ, Kuntz KW, Wigle TJ, Scott MP, Copeland RA, Smith JJ, Chesworth R. ACS Med Chem Lett 7, 134-8, (2016). PMID: 26985287

3.Discovery of A-893, A New Cell-Active Benzoxazinone Inhibitor of Lysine Methyltransferase SMYD2. Sweis RF, Wang Z, Algire M, Arrowsmith CH, Brown PJ, Chiang GG, Guo J, Jakob CG, Kennedy S, Li F, Maag D, Shaw B, Soni NB, Vedadi M, Pappano WN. ACS Med Chem Lett 6, 695-700, (2015). PMID: 26101576

4.Repression of p53 activity by Smyd2-mediated methylation. Huang J, Perez-Burgos L, Placek BJ, Sengupta R, Richter M, Dorsey JA, Kubicek S, Opravil S, Jenuwein T, Berger SL. Nature 444, 629-32, (2006). PMID: 17108971

5.Methylation of the retinoblastoma tumor suppressor by SMYD2. Saddic LA, West LE, Aslanian A, Yates JR 3rd, Rubin SM, Gozani O, Sage J. J Biol Chem 285, 37733-40, (2010). PMID: 20870719

6.Characterizing the Role of SMYD2 in Mammalian Embryogenesis-Future Directions. Jarrell DK, Hassell KN, Crans DC, Lanning S, Brown MA. Vet Sci 7, (2020). PMID: 32408548

7.Smyd2 controls cytoplasmic lysine methylation of Hsp90 and myofilament organization. Donlin LT, Andresen C, Just S, Rudensky E, Pappas CT, Kruger M, Jacobs EY, Unger A, Zieseniss A, Dobenecker MW, Voelkel T, Chait BT, Gregorio CC, Rottbauer W, Tarakhovsky A, Linke WA. Genes Dev 26, 114-9, (2012). PMID: 22241783

8.SMYD2 overexpression is associated with tumor cell proliferation and a worse outcome in human papillomavirus-unrelated nonmultiple head and neck carcinomas. Ohtomo-Oda R, Komatsu S, Mori T, Sekine S, Hirajima S, Yoshimoto S, Kanai Y, Otsuji E, Ikeda E, Tsuda H. Hum Pathol 49, 145-55, (2016). PMID: 26826421

9.Smyd2 is a Myc-regulated gene critical for MLL-AF9 induced leukemogenesis. Bagislar S, Sabo A, Kress TR, Doni M, Nicoli P, Campaner S, Amati B. Oncotarget 7, 66398-66415, (2016). PMID: 27655694

GO terms

Cross References

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