The gp49A gene has extensive sequence conservation with the gp49B gene and provides gp49A protein, a unique member of a large family of activating and inhibitory receptors of the immunoglobulin superfamily
The gp49A gene has extensive sequence conservation with the gp49B gene and provides gp49A protein, a unique member of a large family of activating and inhibitory receptors of the immunoglobulin superfamily
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DOI：
10.1007/s002510050604
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发表时间：
1999-12-01
期刊：
影响因子：
3.2
通讯作者：
Katz, HR
中科院分区：
文献类型：
--
作者：
McCormick, MJ;Castells, MC;Katz, HR
小鼠和人免疫球蛋白（IG）超家族受体的gp 49相关家族成员在其C2型Ig样结构域中具有显著的氨基酸序列同源性，并且包括主要组织相容性复合物I类分子的杀伤细胞Ig样受体（KIR）。我们现在报告的克隆，完整的序列，和组织的小鼠gp 49 A基因编码的唯一成员，这个新认识的家庭没有两个相互排斥的功能基序，即免疫受体酪氨酸为基础的抑制基序（ITIM）或带电的跨膜氨基酸与激活分子的异源二聚化。gp 49 A和gp 49 B基因在5.6个碱基上94%相同，5'侧翼区在1900个核苷酸上94%相同，3'侧翼区在121个核苷酸上97%相同，然后完全分叉; gp 49 B基因编码带有两个ITIM的gp 49 B1。通过流式细胞术用特异性抗体测量，gp 49 A在未成熟的骨髓源性肥大细胞、成熟的血清源性肥大细胞和几种小鼠肥大细胞系上表达。gp 49 A和gp 49 B基因的内含子的实质性序列同一性与外显子的序列同一性相当，建立了作为gp 49相关家族的最同源的基因对，并表明gp 49 A和gp 49 B基因通过重复而产生，随后的突变相对较少。这些发现还首次证明了gp 49 A在肥大细胞上与抑制性gp 49 B1串联表达，并确定gp 49 A基因不是假基因，而是编码具有不同于其他家族成员特征的蛋白质产物。
Members of the gp49-related family of mouse and human immunoglobulin (Ig) superfamily receptors have significant amino acid sequence homology in their C2-type, Ig-like domains and include the killer cell Ig-like receptors (KIRs) for major histocompatibility complex class I molecules. We now report the cloning, complete sequence, and organization of the mouse gp49A gene that encodes the only member of this newly-appreciated family without either of two mutually exclusive functional motifs, namely, immunoreceptor tyrosine-based inhibitory motifs (ITIMs) or a charged transmembrane amino acid for heterodimerization with activation molecules. The gp49A and gp49B genes are 94% identical over 5.6 kilobases, the 5' flanking regions are 94% identical over 1900 nucleotides, and the 3' flanking regions are 97% identical for 121 nucleotides and then diverge completely; the gp49B gene encodes gp49B1 bearing two ITIMs. As measured by flow cytometry with specific antibody, gp49A is expressed on immature bone-marrow-derived mast cells, mature serosal mast cells, and several mouse mast cell lines. The substantial sequence identity of the introns of the gp49A and gp49B genes is comparable to that of the exons, establishing the gene pair as the most homologous of the gp49-related family and suggesting that the gp49A and gp49B genes arose by duplication with relatively little subsequent mutation. The findings also represent the first demonstration that gp49A is expressed on mast cells in tandem with inhibitory gp49B1, and establish that the gp49A gene is not a pseudogene, but rather encodes a protein product with characteristics different from the other family members.