title: Origin of the NEFA and Nuc signal sequences.
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.
authors.affiliation: Department of Immunochemistry, Max Planck Institute for Experimental Medicine, Göttingen, Germany.
authors.forename: A
authors.initials: A
authors.lastname: Karabinos
authors.forename: D
authors.initials: D
authors.lastname: Bhattacharya
authors.forename: H D
authors.initials: HD
authors.lastname: Kratzin
authors.forename: N
authors.initials: N
authors.lastname: Hilschmann
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D001426:Bacterial Proteins / Q000235:genetics* / Q000378:metabolism; D001483:Base Sequence; D002135:Calcium-Binding Proteins; D004247:DNA; D004268:DNA-Binding Proteins / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism; D004720:Endonucleases; D006801:Humans; D006868:Hydrolysis; D051379:Mice; D008836:Micrococcal Nuclease; D008969:Molecular Sequence Data; D009419:Nerve Tissue Proteins; D019913:Nuclear Localization Signals; D000080866:Nucleobindins; D021382:Protein Sorting Signals / Q000235:genetics*; D016415:Sequence Alignment
chemical_list: D001426:Bacterial Proteins; D002135:Calcium-Binding Proteins; D004268:DNA-Binding Proteins; C000630650:NUCB2 protein, human; D009419:Nerve Tissue Proteins; D019913:Nuclear Localization Signals; D000080866:Nucleobindins; D021382:Protein Sorting Signals; C074002:nuc protein, staphylococcus; D004247:DNA; D004720:Endonucleases; D008836:Micrococcal Nuclease