Lysine demethylase 6A (KDM6A), also known as UTX, belongs to the KDM6 family of histone H3 lysine 27 (H3K27) demethylases, which also includes UTY and KDM6B (JMJD3). The KDM6A protein contains six tetratricopeptide repeat (TPR) domains and an enzymatic Jumonji C (JmjC) domain that catalyzes the removal of di- and trimethylation on H3K27. KDM6A physically associates with histone H3 lysine 4 monomethyltransferases MLL3 (KMT2C) and MLL4 (KMT2D). Since its identification as an H3K27 demethylase in 2007, studies have reported KDM6A’s critical roles in cell differentiation, development, and cancer. KDM6A is important for differentiation of embryonic stem cells and development of various tissues. Mutations of KDM6A cause Kabuki syndrome. KDM6A is frequently mutated in cancers and functions as a tumor suppressor. KDM6A is redundant with UTY and functions largely independently of its demethylase activity. It regulates gene expression, likely through the associated transcription factors and MLL3/4 on enhancers. However, KDM6A enzymatic activity is required in certain cellular contexts. Functional redundancy between H3K27 demethylase activities of KDM6A and KDM6B in vivo has yet to be determined. Further understanding of KDM6A functions and working mechanisms will provide more insights into enhancer regulation and may help generate novel therapeutic approaches to treat KDM6A-related diseases.

中文翻译：

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赖氨酸脱甲基酶KDM6A在分化，发展和癌症中的作用。

赖氨酸脱甲基酶6A（KDM6A）也称为UTX，属于组蛋白H3赖氨酸27（H3K27）去甲基酶的KDM6家族，其中还包括UTY和KDM6B（JMJD3）。KDM6A蛋白质包含六个四肽重复（TPR）域和一个酶促Jumonji C（JmjC）域，该结构催化H3K27上二甲基和三甲基化的去除。KDM6A与组蛋白H3赖氨酸4单甲基转移酶MLL3（KMT2C）和MLL4（KMT2D）物理缔合。自从2007年将其鉴定为H3K27脱甲基酶以来，研究报告了KDM6A在细胞分化，发育和癌症中的关键作用。KDM6A对于胚胎干细胞的分化和各种组织的发育非常重要。KDM6A的突变会导致歌舞uki症候群。KDM6A在癌症中经常发生突变，并起着抑癌作用。KDM6A具有UTY的冗余性，其功能很大程度上独立于其脱甲基酶活性。它可能通过相关的转录因子和增强子上的MLL3 / 4调节基因表达。但是，在某些细胞环境中需要KDM6A酶促活性。KDM6A和KDM6B的H3K27脱甲基酶活性之间的功能冗余体内尚未确定。对KDM6A功​​能和工作机制的进一步了解将为增强剂调节提供更多见解，并可能有助于产生新颖的治疗方法来治疗KDM6A相关疾病。