Abstract
SLC9B genes and proteins are members of the sodium/lithium hydrogen antiporter family which function as solute exchangers within cellular membranes of mammalian tissues. SLC9B2 and SLC9B1 amino acid sequences and structures and SLC9B-like gene locations were examined using bioinformatic data from several vertebrate genome projects. Vertebrate SLC9B2 sequences shared 56-98% identity as compared with ∼50% identities with mammalian SLC9B1 sequences. Sequence alignments, key amino acid residues and conserved predicted transmembrane structures were also studied. Mammalian SLC9B2 and SLC9B1 genes usually contained 11 or 12 coding exons with differential tissue expression patterns: SLC9B2, broad tissue distribution; and SLC9B1, being testis specific. Transcription factor binding sites and CpG islands within the human SLC9B2 and SLC9B1 gene promoters were identified. Phylogenetic analyses suggested that SLC9B1 originated in an ancestral marsupial genome from a SLC9B2 gene duplication event.
Highlights
SLC9/NHE gene family members contribute to the maintenance of cellular and intracellular pH homeostasis and are predominantly responsible for the absorption of Na+ ions in the kidney and the GI tract [1,2,3]
The results of the present study indicated that vertebrate SLC9B2 and mammalian SLC9B1 genes and encoded proteins represent a distinct gene and protein family of SLC9B-like proteins which share conserved sequences and active site residues with those reported for SLC9/NHE gene family members, which contribute to the maintenance of cellular and intracellular pH homeostasis and are predominantly responsible for the absorption of Na+ ions in the kidney and the GI tract [1,2,3]
SLC9B2 is encoded by a single gene (SLC9B2) which is more widely expressed in human tissue, with highest levels being observed in kidney, liver and brain, being coexpressed with a proximal gene encoding 3-hydroxybutyrate dehydrogenase (BDH2)
Summary
SLC9/NHE gene family members (sodium lithium carrier 9/ sodium hydrogen exchanger) contribute to the maintenance of cellular and intracellular pH homeostasis and are predominantly responsible for the absorption of Na+ ions in the kidney and the GI tract [1,2,3]. A second gene (NHA1 or NHEDC1; designated as SLC9B1) has been located in tandem with SLC9B2 on human chromosome 4 which is expressed in testis in mammals [7,11]. This is in contrast to Drosophila, for which two SLC9B-like genes (designated as NHA1 and NHA2) are widely expressed in epithelial tissues and play crucial roles in organismal ion homeostasis and as Na+/H+ exchangers [12]
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