Komatsu Masaaki, Chiba Tomoki, Tatsumi Kanako, Iemura Shun-ichiro, Tanida Isei, Okazaki Noriko, Ueno Takashi, Kominami Eiki, Natsume Tohru, Tanaka Keiji
Department of Molecular Oncology, Tokyo Metropolitan Institute of Medical Science, Bunkyo-ku, Tokyo, Japan.
EMBO J. 2004 May 5;23(9):1977-86. doi: 10.1038/sj.emboj.7600205. Epub 2004 Apr 8.
Several studies have addressed the importance of various ubiquitin-like (UBL) post-translational modifiers. These UBLs are covalently linked to most, if not all, target protein(s) through an enzymatic cascade analogous to ubiquitylation, consisting of E1 (activating), E2 (conjugating), and E3 (ligating) enzymes. In this report, we describe the identification of a novel ubiquitin-fold modifier 1 (Ufm1) with a molecular mass of 9.1 kDa, displaying apparently similar tertiary structure, although lacking obvious sequence identity, to ubiquitin. Ufm1 is first cleaved at the C-terminus to expose its conserved Gly residue. This Gly residue is essential for its subsequent conjugating reactions. The C-terminally processed Ufm1 is activated by a novel E1-like enzyme, Uba5, by forming a high-energy thioester bond. Activated Ufm1 is then transferred to its cognate E2-like enzyme, Ufc1, in a similar thioester linkage. Ufm1 forms several complexes in HEK293 cells and mouse tissues, revealing that it conjugates to the target proteins. Ufm1, Uba5, and Ufc1 are all conserved in metazoa and plants but not in yeast, suggesting its potential roles in various multicellular organisms.
多项研究探讨了各种类泛素（UBL）翻译后修饰因子的重要性。这些UBL通过类似于泛素化的酶促级联反应与大多数（如果不是全部）靶蛋白共价连接，该酶促级联反应由E1（激活）、E2（缀合）和E3（连接）酶组成。在本报告中，我们描述了一种新型泛素折叠修饰因子1（Ufm1）的鉴定，其分子量为9.1 kDa，尽管与泛素缺乏明显的序列同一性，但其三级结构明显相似。Ufm1首先在C端被切割以暴露其保守的甘氨酸残基。该甘氨酸残基对其随后的缀合反应至关重要。C端加工后的Ufm1通过形成高能硫酯键被一种新型的类E1酶Uba5激活。然后，激活的Ufm1以类似的硫酯键转移到其同源的类E2酶Ufc1。Ufm1在HEK293细胞和小鼠组织中形成多种复合物，表明它与靶蛋白缀合。Ufm1、Uba5和Ufc1在后生动物和植物中均保守，但在酵母中不保守，这表明它们在各种多细胞生物中具有潜在作用。
