Department of Biological Sciences, University of Maryland Baltimore County, Baltimore, MD 21250, United States.
Department of Biological Sciences, University of Maryland Baltimore County, Baltimore, MD 21250, United States; Marlene and Stewart Greenebaum Comprehensive Cancer Center, University of Maryland School of Medicine, Baltimore, MD 21201, United States.
J Mol Biol. 2024 Apr 1;436(7):168318. doi: 10.1016/j.jmb.2023.168318. Epub 2023 Oct 19.
Within the SET domain superfamily of lysine methyltransferases, there is a well-conserved subfamily, frequently referred to as the Set3 SET domain subfamily, which contain noncanonical SET domains carrying divergent amino acid sequences. These proteins are implicated in diverse biological processes including stress responses, cell differentiation, and development, and their disruption is linked to diseases including cancer and neurodevelopmental disorders. Interestingly, biochemical and structural analysis indicates that they do not possess catalytic methyltransferase activity. At the molecular level, Set3 SET domain proteins appear to play critical roles in the regulation of gene expression, particularly repression and heterochromatin maintenance, and in some cases, via scaffolding other histone modifying activities at chromatin. Here, we explore the common and unique functions among Set3 SET domain subfamily proteins and analyze what is known about the specific contribution of the conserved SET domain to functional roles of these proteins, as well as propose areas of investigation to improve understanding of this important, noncanonical subfamily of proteins.
在赖氨酸甲基转移酶的 SET 结构域超家族中，有一个高度保守的亚家族，通常被称为 Set3 SET 结构域亚家族，其中包含具有不同氨基酸序列的非典型 SET 结构域。这些蛋白质参与多种生物学过程，包括应激反应、细胞分化和发育，其功能失调与癌症和神经发育障碍等疾病有关。有趣的是，生化和结构分析表明它们不具有催化甲基转移酶活性。在分子水平上，Set3 SET 结构域蛋白似乎在基因表达的调控中发挥关键作用，特别是在抑制和异染色质维持方面，在某些情况下，还通过支架将其他组蛋白修饰活性固定在染色质上。在这里，我们探讨了 Set3 SET 结构域亚家族蛋白的常见和独特功能，并分析了保守的 SET 结构域对这些蛋白功能的特定贡献，同时提出了一些研究领域，以增进对这个重要的、非典型蛋白亚家族的理解。
