The novel human protein arginine N-methyltransferase PRMT6 is a nuclear enzyme displaying unique substrate specificity
The novel human protein arginine N-methyltransferase PRMT6 is a nuclear enzyme displaying unique substrate specificity
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DOI：
10.1074/jbc.m108786200
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发表时间：
2002-02-01
影响因子：
4.8
通讯作者：
Bedford, MT
中科院分区：
文献类型：
--
作者：
Frankel, A;Yadav, N;Bedford, MT
蛋白质精氨酸甲基化是真核细胞中普遍存在的一种翻译后修饰，参与信号转导、新生前RNA的代谢和转录激活过程。在人类基因组中寻找蛋白质精氨酸N-甲基转移酶(PRMT)家族成员的过程中，在第一染色体上发现了一个新的基因，编码一个表面甲基转移酶PRMT6。PRMT6的多肽链为41.9 kDa，由其他PRMT酶共有的催化核心序列组成。表达为谷胱甘肽S-转移酶融合蛋白的PrMT6具有I型PRMT活性，能够在富含甘氨酸和精氨酸的重组底物上以递进方式形成不对称的omega-N(G)-单甲基精氨酸和不对称的omega-N(G)，N(G)-二甲基精氨酸衍生物，其比活力为144pmoL甲基转移min(-1)mg(-1)酶。底物特异性的比较表明，PRMT6在功能上不同于先前鉴定的两种I型酶：PRMT1和PRMT4。此外，PRMT6显示出自甲基化活性；它是第一个这样做的PRMT。这种新颖的人类PRMT在与绿色荧光蛋白融合时只驻留在细胞核中，加入了细胞内具有不同功能的酶家族。
Protein arginine methylation is a prevalent posttranslational modification in eukaryotic cells that has been implicated in signal transduction, the metabolism of nascent pre-RNA, and the transcriptional activation processes. In searching the human genome for protein arginine N-methyltransferase (PRMT) family members, a novel gene has been found on chromosome I that encodes for an apparent methyltransferase, PRMT6. The polypeptide chain of PRMT6 is 41.9 kDa consisting of a catalytic core sequence common to other PRMT enzymes. Expressed as a glutathione S-transferase fusion protein, PRMT6 demonstrates type I PRMT activity, capable of forming both omega-N(G)-monomethylarginine and asymmetric omega-N(G),N(G)-dimethylarginine derivatives on the recombinant glycine- and arginine-rich substrate in a processive manner with a specific activity of 144 pmol methyl groups transferred min(-1) mg(-1) enzyme. A comparison of substrate specificity reveals that PRMT6 is functionally distinct from two previously characterized type I enzymes, PRMT1 and PRMT4. In addition, PRMT6 displays automethylation activity; it is the first PRMT to do so. This novel human PRMT, which resides solely in the nucleus when fused to the green fluorescent protein, joins a family of enzymes with diverse functions within cells.