Ishibashi K, Suzuki M, Sasaki S, Imai M
Department of Pharmacology, Jichi Medical School, Minamikawachi, Kawachi, 329-0498, Tochigi, Japan.
Gene. 2001 Feb 7;264(1):87-93. doi: 10.1016/s0378-1119(00)00598-9.
We report here the cloning of eight new cDNAs that encode a family of proteins related to the B-cell-specific antigen CD20, a hematopoietic-cell-specific protein HTm4, and high affinity IgE receptor beta chain (FcvarepsilonRIbeta). They include four clones from human, and another four clones from mouse. They share similar structure (four transmembrane domains) with amino acid identities of 25-40%. Therefore, they represent distinct genes and comprise a gene superfamily. This superfamily is now named membrane-spanning four-domains, subfamily A (the approved symbol is MS4A) to distinguish them from tetraspanins with similar structure. The highest homologies among these proteins are found in the transmembrane domains, especially in the first and second transmembrane domains, and conserved residues are also recognized in the inter-transmembrane domains. In northern blot, they were mostly expressed in lymphoid tissues: thymus and spleen. However, some were expressed in nonlymphoid tissues including brain, heart, kidney, liver, testis, lung, GI tracts, and pancreas. They may represent proteins functioning either directly as ligand-gated ion channels or as essential components of such channels. The identification of this relatively large gene family in various tissues will allow the further elucidation of physiological significance of this gene family, that is currently unclear.
我们在此报告克隆了八个新的cDNA，它们编码一类与B细胞特异性抗原CD20、造血细胞特异性蛋白HTm4以及高亲和力IgE受体β链（FcεRIβ）相关的蛋白质家族。其中包括四个来自人类的克隆，以及另外四个来自小鼠的克隆。它们具有相似的结构（四个跨膜结构域），氨基酸同源性为25% - 40%。因此，它们代表不同的基因，构成一个基因超家族。这个超家族现在被命名为跨膜四区A亚家族（批准符号为MS4A），以将它们与结构相似的四跨膜蛋白区分开来。这些蛋白质之间的最高同源性存在于跨膜结构域，尤其是第一和第二个跨膜结构域，并且在跨膜结构域之间也识别出保守残基。在Northern印迹分析中，它们大多在淋巴组织（胸腺和脾脏）中表达。然而，有些也在非淋巴组织中表达，包括脑、心脏、肾脏、肝脏、睾丸、肺、胃肠道和胰腺。它们可能代表直接作为配体门控离子通道发挥作用的蛋白质，或者作为此类通道的重要组成部分。在各种组织中鉴定出这个相对较大的基因家族将有助于进一步阐明目前尚不清楚的该基因家族的生理意义。
