Characterization of human TMEM16G gene in silico.
Characterization of human TMEM16G gene in silico.
复制标题
人类 TMEM16G 基因的计算机表征。
DOI：
10.3892/ijmm.14.4.759
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发表时间：
2004
影响因子：
5.4
通讯作者：
M. Katoh
中科院分区：
文献类型：
--
作者：
Masuko Katoh;M. Katoh
TMEM16A、TMEM16B、TMEM16C、TMEM16D、TMEM16E、TMEM16F和TP53I5是TMEM16家族的8个跨膜蛋白，N-末端和C-末端面向细胞质。人染色体11q13.3处的TMEM16A基因在头颈部肿瘤中扩增，人染色体11p14.3处的TMEM16E基因在颌骨骨干发育不良(GDD)中发生突变。Ngep基因(NM_207031.1)来源于小鼠Tem16g基因。在这里，我们利用生物信息学的方法对人类TMEM16G基因进行了研究。TMEM16G基因位于人类染色体2q37.3，由25个外显子组成。种内比较基因组学分析表明，PASK-PPP1R7-TMEM16G-HDLBP-NEDD5基因座是唯一不存在近似区的区域。TMEM16G mRNA在正常前列腺癌和前列腺癌中优先表达。通过组装TMEM16G基因的25个外显子，确定了TMEM16G基因的完整编码序列。人TMEM16G基因编码932个氨基酸的TMEM16G蛋白，含有TM16H1、TM16H2和TM16H3结构域。比较蛋白质组学显示，人TMEM16G在进化过程中发生了T844N氨基酸替换。TMHMM2程序预测小鼠Tme16G和人造人TMEM16G(844T)是8个跨膜蛋白，而野生型人TMEM16G(844N)是7个跨膜蛋白。这些事实表明，人TMEM16G第844位密码子的氨基酸替换导致了第八个跨膜螺旋的错误折叠。膜拓扑结构改变的人TMEM16G可能与TMEM16家族的其他成员相比显示出功能上的差异。
TMEM16A, TMEM16B, TMEM16C, TMEM16D, TMEM16E, TMEM16F and TP53I5 are TMEM16 family eight-transmembrane proteins with N- and C-terminal tails facing the cytoplasm. TMEM16A gene at human chromosome 11q13.3 is amplified in head and neck tumors, and TMEM16E gene at human chromosome 11p14.3 is mutated in gnathodiaphyseal dysplasia (GDD). Ngep cDNA (NM_207031.1) is derived from mouse Tmem16g gene. Here, we characterized human TMEM16G gene by using bioinformatics. TMEM16G gene, consisting of 25 exons, was located at human chromosome 2q37.3. Intra-species comparative genomics revealed that the PASK-PPP1R7-TMEM16G-HDLBP-NEDD5 locus was the unique region without paralogous region. TMEM16G mRNA was preferentially expressed in normal prostate and prostate cancer. Complete coding sequence of TMEM16G cDNA was determined by assembling 25 exons of TMEM16G gene. Human TMEM16G gene was found to encode 932-amino-acid TMEM16G protein with TM16H1, TM16H2 and TM16H3 domains. Comparative proteomics revealed that T844N amino-acid substitution occurred in human TMEM16G during evolution. TMHMM2 program predicted that mouse Tmem16g and artificial human TMEM16G (844T) were eight-transmembrane proteins, but that wild-type human TMEM16G (844N) was a seven-transmembrane protein. These facts indicate that amino-acid substitution at codon 844 of human TMEM16G resulted in the mis-folding of the eighth transmembrane helix. Human TMEM16G with altered membrane topology might show functional divergence compared with other members of the TMEM16 family.