Origin of the NEFA and Nuc Signal Sequences |
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Authors: | Anton Karabinos Debashish Bhattacharya Hartmut D Kratzin Norbert Hilschmann |
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Institution: | Department of Immunochemistry, Max Planck Institute for Experimental Medicine, Hermann-Rein-Stra?e 3, 37075 G?ttingen, Germany, DE Department of Biological Sciences, University of Iowa, 138 Biology Building, Iowa City, IA 52242-1324, USA, US
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Abstract: | 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.
Received: 20 February 1997 / Accepted: 28 July 1997 |
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Keywords: | : EF-hand — Gene duplication — Molecular evolution — Nuc — Secretory proteins |
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