The SLC13 gene family of sodium sulphate/carboxylate cotransporters

The SLC13 gene family consist of five sequence-related members that have been identified in a variety of animals, plants, yeast and bacteria. Proteins encoded by these genes are divided into two functionally unrelated groups: the Na⁺-sulphate (NaS) cotransporters and the Na⁺-carboxylate (NaC) cotransporters. Members of this family include the renal Na⁺-dependent inorganic sulphate transporter-1 (NaSi-1, SLC13A1), the Na⁺-dependent dicarboxylate transporters NaDC-1/SDCT1 (SLC13A2), NaDC-3/SDCT2 (SLC13A3), the sulphate transporter-1 (SUT-1, SLC13A4) and the Na⁺-coupled citrate transporter (NaCT, SLC13A5). The general characteristics of the SLC13 proteins are that they encode multi-spanning proteins with 8–13 transmembrane domains, have a wide tissue distribution with most being expressed in the epithelial cells of the kidney and the gastrointestinal tract. They are Na⁺-coupled symporters, DIDS-insensitive, with strong cation preference for Na⁺, with a Na⁺:anion coupling ratio of around 3:1 and have a substrate preference for divalent anions, which include tetraoxyanions (for the NaS cotransporters) or Krebs cycle intermediates, including mono-, di-, and tri-carboxylates (for the NaC cotransporters). The purpose of this review is to provide an update on the most recent advances and to summarize the biochemical, physiological and structural aspects of the vertebrate SLC13 gene family.