Petkowski Janusz J, Bonsignore Lindsay A, Tooley John G, Wilkey Daniel W, Merchant Michael L, Macara Ian G, Schaner Tooley Christine E
*Department of Biology (D-BIOL), Institute of Biochemistry (IBC), ETH Zurich, Zurich 8093, Switzerland.
Biochem J. 2013 Dec 15;456(3):453-62. doi: 10.1042/BJ20131163.
NRMT (N-terminal regulator of chromatin condensation 1 methyltransferase) was the first eukaryotic methyltransferase identified to specifically methylate the free α-amino group of proteins. Since the discovery of this N-terminal methyltransferase, many new substrates have been identified and the modification itself has been shown to regulate DNA-protein interactions. Sequence analysis predicts one close human homologue of NRMT, METTL11B (methyltransferase-like protein 11B, now renamed NRMT2). We show in the present paper for the first time that NRMT2 also has N-terminal methylation activity and recognizes the same N-terminal consensus sequences as NRMT (now NRMT1). Both enzymes have similar tissue expression and cellular localization patterns. However, enzyme assays and MS experiments indicate that they differ in their specific catalytic functions. Although NRMT1 is a distributive methyltransferase that can mono-, di- and tri-methylate its substrates, NRMT2 is primarily a monomethylase. Concurrent expression of NRMT1 and NRMT2 accelerates the production of trimethylation, and we propose that NRMT2 activates NRMT1 by priming its substrates for trimethylation.
NRMT（染色质凝聚1甲基转移酶N端调节因子）是首个被鉴定出能特异性甲基化蛋白质游离α-氨基的真核甲基转移酶。自这种N端甲基转移酶被发现以来，已鉴定出许多新底物，并且这种修饰本身已被证明可调节DNA-蛋白质相互作用。序列分析预测NRMT有一个紧密的人类同源物，即METTL11B（甲基转移酶样蛋白11B，现更名为NRMT2）。我们在本文中首次表明，NRMT2也具有N端甲基化活性，并且识别与NRMT（现称NRMT1）相同的N端共有序列。这两种酶具有相似的组织表达和细胞定位模式。然而，酶活性测定和质谱实验表明它们的具体催化功能有所不同。虽然NRMT1是一种分布性甲基转移酶，可将其底物单甲基化、双甲基化和三甲基化，但NRMT2主要是一种单甲基化酶。NRMT1和NRMT2的同时表达会加速三甲基化的产生，并且我们提出NRMT2通过使其底物为三甲基化做好准备来激活NRMT1。
