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Bioinformatic Characterization of the Trimeric Intracellular Cation-Specific Channel Protein Family

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Abstract

Trimeric intracellular cation-specific (TRIC) channels are integral to muscle excitation–contraction coupling. TRIC channels provide counter-ionic flux when calcium is rapidly transported from intracellular stores to the cell cytoplasm. Until recently, knowledge of the presence of these proteins was limited to animals. We analyzed the TRIC family and identified a profusion of prokaryotic family members with topologies and motifs similar to those of their eukaryotic counterparts. Prokaryotic members far outnumber eukaryotic members, and although none has been functionally characterized, the evidence suggests that they function as secondary carriers. The presence of fused N- or C-terminal domains of known biochemical functions as well as genomic context analyses provide clues about the functions of these prokaryotic homologs. They are proposed to function in metabolite (e.g., amino acid/nucleotide) efflux. Phylogenetic analysis revealed that TRIC channel homologs diverged relatively early during evolutionary history and that horizontal gene transfer was frequent in prokaryotes but not in eukaryotes. Topological analyses of TRIC channels revealed that these proteins possess seven putative transmembrane segments (TMSs), which arose by intragenic duplication of a three-TMS polypeptide-encoding genetic element followed by addition of a seventh TMS at the C terminus to give the precursor of all current TRIC family homologs. We propose that this family arose in prokaryotes.

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Acknowledgment

We acknowledge the computational expertise and instructive efforts of Dorjee G. Tamang, Dr. Joshua Kohn for useful advice on phylogenetic tree construction and analysis and the NIH (GM077402) for financial support.

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  1. Division of Biological Sciences, University of California at San Diego, La Jolla, CA, 92093-0116, USA

    Abe L. F. Silverio & Milton H. Saier Jr.

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  1. Abe L. F. Silverio
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Correspondence to Milton H. Saier Jr..

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Silverio, A.L.F., Saier, M.H. Bioinformatic Characterization of the Trimeric Intracellular Cation-Specific Channel Protein Family. J Membrane Biol 241, 77–101 (2011). https://doi.org/10.1007/s00232-011-9364-8

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