Karabinos A, Bhattacharya D, Kratzin H D, Hilschmann N
Department of Immunochemistry, Max Planck Institute for Experimental Medicine, Göttingen, Germany.
J Mol Evol. 1998 Mar;46(3):327-33. doi: 10.1007/pl00006309.
The human protein NEFA binds calcium, contains a leucine zipper repeat that does not form a homodimer, and is proposed (along with the homologous Nuc protein) to have a common evolutionary history with an EF-hand ancestor. We have isolated and characterized the N-terminal domain of NEFA that contains a signal sequence inferred from both endoproteinase Asp-N (Asp-N) and tryptic digests. Analysis of this N-terminal sequence shows significant similarity to the conserved multiple domains of the mitochondrial carrier family (MCF) proteins. The leader sequence of Nuc is, however, most similar to the signal sequences of membrane and/or secreted proteins (e.g., mouse insulin-like growth factor receptor). We suggest that the divergent NEFA and Nuc N-terminal sequences may have independent origins and that the common high hydrophobicity governs their targeting to the ER. These results provide insights into signal sequence evolution and the multiple origins of protein targeting.
人类蛋白质NEFA可结合钙，含有一个不形成同二聚体的亮氨酸拉链重复序列，并且（与同源的Nuc蛋白一起）被认为与EF手型祖先具有共同的进化历史。我们已经分离并鉴定了NEFA的N端结构域，该结构域包含从内蛋白酶Asp-N（Asp-N）和胰蛋白酶消化产物推断出的信号序列。对该N端序列的分析表明，它与线粒体载体家族（MCF）蛋白的保守多个结构域具有显著相似性。然而，Nuc的前导序列与膜和/或分泌蛋白（例如小鼠胰岛素样生长因子受体）的信号序列最为相似。我们认为，不同的NEFA和Nuc N端序列可能有独立的起源，并且共同的高疏水性决定了它们靶向内质网的方向。这些结果为信号序列的进化以及蛋白质靶向的多种起源提供了见解。
