Höglund Pär J, Adzic Dijana, Scicluna Sara J, Lindblom Jonas, Fredriksson Robert
Department of Neuroscience, Uppsala University, BMC, Box 593, 751 24 Uppsala, Sweden.
Biochem Biophys Res Commun. 2005 Oct 14;336(1):175-89. doi: 10.1016/j.bbrc.2005.08.048.
Tremendous amount of primary sequence information has been made available from the genome sequencing projects, although a complete annotation and identification of all genes is still far from being complete. Here, we present the identification of two new human genes from the pharmacologically important family of transporter proteins, solute carriers family 6 (SLC6). These were named SLC6A17 and SLC6A18 by HUGO. The human repertoire of SLC6 proteins now consists of 19 functional members and four pseudogenes. We also identified the corresponding orthologues and additional genes from mouse and rat genomes. Detailed phylogenetic analysis of the entire family of SLC6 proteins in mammals shows that this family can be divided into four subgroups. We used Hidden Markov Models for these subgroups and identified in total 430 unique SLC6 proteins from 10 animal, one plant, two fungi, and 196 bacterial genomes. It is evident that SLC6 proteins are present in both animals and bacteria, and that three of the four subfamilies of mammalian SLC6 proteins are present in Caenorhabditis elegans, showing that these subfamilies are evolutionary very ancient. Moreover, we performed tissue localization studies on the entire family of SLC6 proteins on a panel of 15 rat tissues and further, the expression of three of the new genes was studied using quantitative real-time PCR showing expression in multiple central and peripheral tissues. This paper presents an overall overview of the gene repertoire of the SLC6 gene family and its expression profile in rats.
尽管对所有基因进行完整注释和鉴定仍远未完成,但基因组测序项目已提供了大量的一级序列信息。在此,我们报告了从药理学上重要的转运蛋白家族——溶质载体家族6(SLC6)中鉴定出两个新的人类基因。HUGO将它们命名为SLC6A17和SLC6A18。SLC6蛋白的人类成员现在包括19个功能成员和4个假基因。我们还从小鼠和大鼠基因组中鉴定出了相应的直系同源基因和其他基因。对哺乳动物中整个SLC6蛋白家族进行的详细系统发育分析表明,该家族可分为四个亚组。我们针对这些亚组使用了隐马尔可夫模型,并从10种动物、1种植物、2种真菌和196种细菌基因组中总共鉴定出430种独特的SLC6蛋白。显然,SLC6蛋白存在于动物和细菌中,并且哺乳动物SLC6蛋白的四个亚家族中的三个存在于秀丽隐杆线虫中,这表明这些亚家族在进化上非常古老。此外,我们对15种大鼠组织中的整个SLC6蛋白家族进行了组织定位研究,并且进一步使用定量实时PCR研究了三个新基因的表达,结果显示它们在多个中枢和外周组织中均有表达。本文全面概述了SLC6基因家族的基因组成及其在大鼠中的表达谱。