Zenz T, Roessner A, Thomas A, Fröhling S, Döhner H, Calabretta B, Dahéron L
Department of Medicine III, University Hospital Ulm, Ulm, Germany.
Genes Immun. 2004 Mar;5(2):109-16. doi: 10.1038/sj.gene.6364044.
The family of immune associated nucleotide binding proteins (Ian) is a distinct family of GTP-binding proteins conserved in plants, mice, rats and humans that are associated with immune functions, suggesting involvement in conserved defense mechanisms. Recently, the rat Ian4 (rIan4) was cloned and it appears to be identical to the gene Iddm1/lyp responsible for severe lymphopenia and the development of insulin-dependent diabetes in the BB-DP rat. Here we describe the characterization of a new human member of the Ian family: hIan5. hIan5 is highly homologous to rIan4, has a predicted molecular weight of 35 kDa and contains distinct G motifs of GTP-binding proteins (G-1 to G-4) in the N-terminus. Human Ian5 is anchored to the mitochondria by the hydrophobic COOH-terminal domain. Human Ian5 is highly expressed in lymph node and spleen. Different blood fractions show high hIan5 expression in CD4- and CD8-positive T cells and monocytes, but not in B lymphocytes. In contrast, in B-CLL (chronic lymphocytic leukemia) and mantle cell lymphoma samples, hIan5 mRNA was upregulated. The current data underline the role of hIan5 in T-lymphocyte development and function, and for the first time suggest that upregulation of Ian proteins is associated with B-cell malignancy, possibly by inhibiting apoptosis.
免疫相关核苷酸结合蛋白（Ian）家族是一类独特的GTP结合蛋白家族，在植物、小鼠、大鼠和人类中保守存在，与免疫功能相关，提示其参与保守的防御机制。最近，大鼠Ian4（rIan4）被克隆出来，它似乎与负责BB-DP大鼠严重淋巴细胞减少和胰岛素依赖型糖尿病发展的Iddm1/lyp基因相同。在此，我们描述了Ian家族一个新的人类成员：hIan5的特征。hIan5与rIan4高度同源，预测分子量为35 kDa，在N端含有GTP结合蛋白的不同G基序（G-1至G-4）。人Ian5通过疏水性COOH末端结构域锚定在线粒体上。人Ian5在淋巴结和脾脏中高度表达。不同血液组分显示，hIan5在CD4和CD8阳性T细胞及单核细胞中高表达，但在B淋巴细胞中不表达。相反，在B细胞慢性淋巴细胞白血病（B-CLL）和套细胞淋巴瘤样本中，hIan5 mRNA上调。目前的数据强调了hIan5在T淋巴细胞发育和功能中的作用，并且首次表明Ian蛋白的上调与B细胞恶性肿瘤相关，可能是通过抑制细胞凋亡实现的。
