Molecular Evolution of Hemojuvelin and the Repulsive Guidance Molecule Family |
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Authors: | Laura Marie Camus Lisa A. Lambert |
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Affiliation: | (1) Department of Biology, Chatham University, Woodland Road, Pittsburgh, PA 15232, USA |
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Abstract: | Repulsive guidance molecules (RGMs) are found in vertebrates and chordates and are involved in embryonic development and iron homeostasis. Members of this family are GPI-linked membrane proteins that contain an N-terminal signal peptide, a C-terminal propeptide, and a conserved RGD motif. Vertebrates are known to possess three paralogues; RGMA and RGMB (sometimes called Dragon) are expressed in the nervous system and are thought to play various roles in neural development. Hemojuvelin (HJV; also called repulsive guidance molecule c, RGMC) is the third member of this family, and mutations in this gene result in a form of juvenile hemochromatosis (type 2A). Phylogenetic analyses of 55 different RGM family sequences from 21 different species support the existence of a novel gene, found only in fish, which we have labeled RGMD. The pattern of conserved residues in each family identifies new candidates for important functional roles, including ligand binding. [Reviewing Editor: Dr. Gail Simmons] |
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Keywords: | Hemojuvelin Repulsive guidance molecule Bone morphogenetic protein Hemochromatosis Iron homeostasis RGD motif Cell signaling |
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