Sibthorpe Dean, Baker Anne-Marie, Gilmartin Brian J, Blackwell Jenefer M, White Jacqueline K
Division of Environmental and Evolutionary Biology, The Gatty Marine Laboratory, University of St. Andrews, Fife KY16 8LB, UK.
DNA Cell Biol. 2004 Jan;23(1):45-58. doi: 10.1089/104454904322745925.
To study the evolution of the solute carrier family 11 (slc11; formerly Nramp) protein, we isolated and characterized two paralogs from the pufferfish Takifugu rubripes (Fugu). These teleost genes, designated Fugu slc11a-a and Fugu slc11a-b, comprise open reading frames of 1743 nucleotides (581 amino acids) and 1662 nt (554 aa), respectively. The proteins are 81% similar, and both exhibit signature features of the slc11 family of proteins including 12 transmembrane domains, a conserved transport motif and a glycosylated loop. Both Fugu paralogs are more Slc11a2-like based on sequence homology and phylogenetic studies. Analysis of gene environment placed both in the proximity of multiple loci syntenic to human chromosome 12q13, that is, within a SLC11A2 gene environment. However, Fugu slc11a-a also gave one match with chromosome 2q35, where human SLC11A1 resides. Functional diversification was suggested by differences in tissue distribution and subcellular localization. Fugu slc11a-a exhibits a restricted expression profile and a complex subcellular localization, including LAMP1 positive late endosomes/lysosomes in transiently transfected mouse macrophages. Fugu slc11a-b is expressed ubiquitously and localizes solely to late endosomes/lysosomes. This comparative analysis extends our understanding of the evolution and function of this important family of divalent cation transporters. [Sequence data from this article have been deposited with the EMBL/GenBank Data Libraries under accession nos. AJ496547/8/9 and AJ496550.]
为了研究溶质载体家族11（slc11；原称Nramp）蛋白的进化，我们从河豚红鳍东方鲀（Fugu）中分离并鉴定了两个旁系同源基因。这两个硬骨鱼基因，分别命名为Fugu slc11a-a和Fugu slc11a-b，其开放阅读框分别为1743个核苷酸（581个氨基酸）和1662个核苷酸（554个氨基酸）。这两种蛋白质的相似度为81%，并且都具有slc11家族蛋白质的标志性特征，包括12个跨膜结构域、一个保守的转运基序和一个糖基化环。基于序列同源性和系统发育研究，河豚的两个旁系同源基因都更类似于Slc11a2。对基因环境的分析表明，这两个基因都位于与人类12号染色体q13区域同线的多个基因座附近，即在SLC11A2基因环境中。然而，Fugu slc11a-a与人类SLC11A1所在的2号染色体q35区域也有一个匹配。组织分布和亚细胞定位的差异表明了功能的分化。Fugu slc11a-a表现出有限的表达谱和复杂的亚细胞定位，包括在瞬时转染的小鼠巨噬细胞中的LAMP1阳性晚期内体/溶酶体。Fugu slc11a-b广泛表达，仅定位于晚期内体/溶酶体。这种比较分析扩展了我们对这个重要的二价阳离子转运蛋白家族的进化和功能的理解。[本文的序列数据已存入EMBL/GenBank数据库，登录号为AJ496547/8/9和AJ496550。]
