Jumonji C domain-containing (JMJD) proteins are mostly epigenetic regulators that demethylate histones. However, a hitherto neglected subfamily of JMJD proteins, evolutionarily distant and characterized by their relatively small molecular weight, exerts different functions by hydroxylating proteins and RNA. Recently, unsuspected proteolytic and tyrosine kinase activities were also ascribed to some of these small JMJD proteins, further increasing their enzymatic versatility. Here, we discuss the ten human small JMJD proteins (HIF1AN, HSPBAP1, JMJD4, JMJD5, JMJD6, JMJD7, JMJD8, RIOX1, RIOX2, TYW5) and their diverse physiological functions. In particular, we focus on the roles of these small JMJD proteins in cancer and other maladies and how they are modulated in diseased cells by an altered metabolic milieu, including hypoxia, reactive oxygen species and oncometabolites. Because small JMJD proteins are enzymes, they are amenable to inhibition by small molecules and may represent novel targets in the therapy of cancer and other diseases.

中文翻译：

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JMJD蛋白家族的小成员：酶珠宝还是金币？

含有Jumonji C结构域（JMJD）的蛋白质大部分是使组蛋白去甲基化的表观遗传调节剂。然而，迄今为止被忽视的JMJD蛋白亚家族，在进化上遥远并且以其相对较小的分子量为特征，通过使蛋白和RNA羟基化而发挥不同的功能。最近，这些小JMJD蛋白中的一些蛋白也被认为具有蛋白水解和酪氨酸激酶活性，这进一步增加了它们的酶促多功能性。在这里，我们讨论了十种人类小JMJD蛋白（HIF1AN，HSPBAP1，JMJD4，JMJD5，JMJD6，JMJD7，JMJD8，RIOX1，RIOX2，TYW5）及其多种生理功能。特别是，我们关注这些小的JMJD蛋白在癌症和其他疾病中的作用，以及它们如何通过改变的代谢环境（包括缺氧，活性氧和代谢代谢物。因为小的JMJD蛋白是酶，所以它们易于被小分子抑制，并且可能代表癌症和其他疾病治疗中的新靶标。