STK19 was originally identified as a manganese-dependent serine/threonine-specific protein kinase, but its function has been highly debated. Here, the crystal structure of STK19 revealed that it does not contain a kinase domain, but three intimately packed winged helix (WH) domains. The third WH domain mediated homodimerization and double-stranded DNA binding, both being important for its nuclear localization. STK19 participated in the nucleotide excision repair (NER) and mismatch repair (MMR) pathways by recruiting damage repair factors such as RPA2 and PCNA. STK19 also bound double-stranded RNA through the DNA-binding interface and regulated the expression levels of many mRNAs. Furthermore, STK19 knockdown cells exhibited very slow cell proliferation, which cannot be rescued by dimerization or DNA-binding mutants. Therefore, this work concludes that STK19 is highly unlikely to be a kinase but a DNA/RNA-binding protein critical for DNA damage repair (DDR) and cell proliferation. To prevent further confusions, we renamed this protein as TWH19 (Tandem Winged Helix protein formerly known as STK19).

中文翻译：

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STK19 是一种对 DNA 损伤修复和细胞增殖至关重要的 DNA/RNA 结合蛋白


STK19 最初被鉴定为锰依赖性丝氨酸/苏氨酸特异性蛋白激酶，但其功能一直存在高度争议。在这里，STK19 的晶体结构显示它不包含激酶结构域，而是三个紧密排列的翼状螺旋 （WH） 结构域。第三个 WH 结构域介导同源二聚化和双链 DNA 结合，这两者都对其核定位很重要。STK19 通过募集 RPA2 和 PCNA 等损伤修复因子参与核苷酸切除修复 （NER） 和错配修复 （MMR） 通路。STK19 还通过 DNA 结合界面结合双链 RNA，并调节许多 mRNA 的表达水平。此外，STK19 敲低细胞表现出非常缓慢的细胞增殖，无法通过二聚化或 DNA 结合突变体来挽救。因此，这项工作得出结论，STK19 极不可能是一种激酶，而是一种对 DNA 损伤修复 （DDR） 和细胞增殖至关重要的 DNA/RNA 结合蛋白。为了防止进一步的混淆，我们将这种蛋白质重命名为 TWH19（串联翼螺旋蛋白，以前称为 STK19）。