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2.A.47 The Divalent Anion:Na+ Symporter (DASS) Family

Functionally characterized proteins of the DASS family (also called the SLC13 family) transport (1) organic di- and tricarboxylates of the Krebs Cycle as well as dicarboxylate amino acid, (2) inorganic sulfate and (3) phosphate. These proteins are found in Gram-negative bacteria, cyanobacteria, archaea, plant chloroplasts, yeast and animals. They vary in size from 432 amino acyl residues (M. jannaschii) to 923 residues (Saccharomyces cerevisiae). The three S. cerevisiae proteins are large (881-923 residues); the animal proteins are substantially smaller (539-616 residues), and the bacterial proteins are still smaller (461-612 residues). They exhibit 11-14 putative transmembrane α-helical spanners (TMSs). An 11 TMS model for the animal NaDC-1 and hNaSi-1 carriers has been proposed (Li and Pajor, 2003; Pajor, 1999). Two serine residues in the human sulfate transporter, hNaSi-1 (Q9BZW2), one in TMS 5 and one in TMS 6, are required for sulfate transport (Li and Pajor, 2003). The former carrier and the other NaDC isoforms cotransport 3 Na+ with each dicarboxylate. Protonated tricarboxylates are also cotransported with 3 Na+. Several organisms possess multiple paralogues of the DASS family (e.g., 4 for E. coli; 2 for H. influenzae, 3 for S. cerevisiae, and at least 4 for C. elegans).

Proteins of the DASS family are divided into two groups of transporters with distinct anion specificities: the Na+-sulfate (NaS) cotransporters and the Na+-carboxylate (NaC) cotransporters. Mammalian members of this family  are: SLC13A1 (NaS1), SLC13A2 (NaC1), SLC13A3 (NaC3), SLC13A4 (NaS2) and SLC13A5 (NaC2) (Markovich 2012). DASS family proteins encode plasma membrane polypeptides with 8-13 putative transmembrane domains, and are expressed in a variety of tissues. They are all Na+-coupled symporters. The Na+:anion coupling ratio is 3:1, indicative of electrogenic properties. They have a substrate preference for divalent anions, which include tetra-oxyanions for the NaS cotransporters or Krebs cycle intermediates (including mono-, di- and tricarboxylates) for the NaC cotransporters. The molecular and cellular mechanisms underlying the biochemical, physiological and structural properties of DASS family members have been reviewed (Markovich, 2012).

The phylogenetic tree for the DASS family reveals six clusters as follows: (1) all animal homologues; (2) all yeast proteins; (3) a functionally uncharacterized protein from Ralstonia eutrophus; (4) three E. coli proteins plus one from H. influenzae and one from spinach chloroplasts (the SodiT1 oxoglutarate:malate translocator); (5) an E. coli Orf that clusters loosely with a sulfur deprivation regulated protein of Synechocystis, and (6) an M. jannaschii protein that clusters loosely with an H. influenzae Orf.

Distant homologues of DASS family proteins may include members of the Ars (arsenite exporter) (TC #3.A.4) family as well as the NhaB (TC #2.A.34) and NhaC (TC #2.A.35) Na+/H+ antiporter families. The DASS family is therefore a member of the ion transporter (IT) superfamily (Rabus et al., 1999).

The generalized transport reaction catalyzed by the DASS family proteins is probably:

Anion2- (out) + nM+ [Na+ or H+] (out) → Anion2- (in) + nM+ (in).


This family belongs to the: IT Superfamily.

References associated with 2.A.47 family:

and Markovich D. (2014). Na+-sulfate cotransporter SLC13A1. Pflugers Arch. 466(1):131-7. 24193406
Beck, L. and D. Markovich. (2000). The mouse Na+-sulfate cotransporter gene Nas1. Cloning, tissue distribution, gene structure, chromosomal assignment, and transcriptional regulation by vitamin D. J. Biol. Chem. 275: 11880-11890. 10766815
Bergeron, M.J., B. Clémençon, M.A. Hediger, and D. Markovich. (2013). SLC13 family of Na⁺-coupled di- and tri-carboxylate/sulfate transporters. Mol Aspects Med 34: 299-312. 23506872
Bun-Ya, M., K. Shikata, S. Nakade, C. Yompakdee, S. Harashima, and Y. Oshima. (1996). Two new genes, PHO86 and PHO87, involved in inorganic phosphate uptake in Saccharomyces cerevisiae. Curr. Genet. 29: 344-351. 8598055
Chen, X.-Z., C. Shayakul, U.V. Berger, W. Tian, and M.A. Hediger. (1998). Characterization of a rat Na+-dicarboxylate cotransporter. J. Biol. Chem. 273: 29072-20981. 9694847
Ebbighausen, H., B. Weil, and R. Krämer. (1991). Na+-dependent succinate uptake in Corynebacterium glutamicum. FEMS Microbiol. Lett. 61: 61-65. 2004698
Estrella, L.A., S. Krishnamurthy, C.R. Timme, and M. Hampsey. (2008). The Rsp5 E3 ligase mediates turnover of low affinity phosphate transporters in Saccharomyces cerevisiae. J. Biol. Chem. 283: 5327-5334. 18165238
Fei, Y.-J., K. Inoue, and V. Ganapathy. (2003). Structural and functional characteristics of two sodium-coupled dicarboxylate transporters (ceNaDC1 and ceNaDC2) from Caenorhabditis elegans and their relevance to life span. J. Biol. Chem. 278: 6136-6144. 12480943
Gisin, J., A. Müller, Y. Pfänder, S. Leimkühler, F. Narberhaus, and B. Masepohl. (2010). A Rhodobacter capsulatus member of a universal permease family imports molybdate and other oxyanions. J. Bacteriol. 192: 5943-5952. 20851900
Hall, J.A. and A.M. Pajor. (2005). Functional characterization of a Na+-coupled dicarboxylate carrier protein from Staphylococcus aureus. J. Bacteriol. 187: 5189-5194. 16030212
Hall, J.A. and A.M. Pajor. (2007). Functional reconstitution of SdcS, a Na+-coupled dicarboxylate carrier protein from Staphylococcus aureus. J. Bacteriol. 189: 880-885. 17114260
Inoue, K., L. Zhuang, D.M. Maddox, S.B. Smith, and V. Ganapathy. (2002). Structure, function, and expression pattern of a novel sodium-coupled citrate transporter (NaCT) cloned from mammalian brain. J. Biol. Chem. 277: 39469-39476. 12177002
Inoue, K., Y.J. Fei, W. Huang, L. Zhuang, Z. Chen, and V. Ganapathy. (2002). Functional identity of Drosophila melanogaster Indy as a cation-independent, electroneutral transporter for tricarboxylic acid-cycle intermediates. Biochem. J. 367: 313-319. 12186628
Jimenez V. and Docampo R. (2015). TcPho91 is a contractile vacuole phosphate sodium symporter that regulates phosphate and polyphosphate metabolism in Trypanosoma cruzi. Mol Microbiol. 97(5):911-25. 26031800
Joshi, A.D. and A.M. Pajor. (2009). Identification of Conformationally Sensitive Amino Acids in the Na+/Dicarboxylate Symporter (SdcS) (dagger). Biochemistry 48: 3017-3024. 19260674
Kekuda, R., H.P. Wang, W. Huang, A.M. Pajor, F.H. Leibach, L.D. Devoe, P.D. Prasad, and V. Ganapathy. (1999). Primary structure and functional characteristics of a mammalian sodium-coupled high affinity dicarboxylate transporter. J. Biol. Chem. 274: 3422-3429. 9920886
Kim, O.B. and G. Unden. (2006). The L-Tartrate/Succinate antiporter TtdT (YgjE) of L-Tartrate fermentation in Escherichia coli. J. Bacteriol. 189(5): 1597-1603. 17172328
Kim, O.B., J. Reimann, H. Lukas, U. Schumacher, J. Grimpo, P. Dünnwald, and G. Unden. (2009). Regulation of tartrate metabolism by TtdR and relation to the DcuS-DcuR-regulated C4-dicarboxylate metabolism of Escherichia coli. Microbiology 155: 3632-3640. 19661178
Kovermann, P., S. Meyer, S. Hörtensteiner, C. Picco, J. Scholz-Starke, S. Ravera, Y. Lee, and E. Martinoia. (2007). The Arabidopsis vacuolar malate channel is a member of the ALMT family. Plant J. 52: 1169-1180. 18005230
Lazard, M., S. Blanquet, P. Fisicaro, G. Labarraque, and P. Plateau. (2010). Uptake of selenite by Saccharomyces cerevisiae involves the high and low affinity orthophosphate transporters. J. Biol. Chem. 285: 32029-32037. 20688911
Lee, S., P.A. Dawson, A.K. Hewavitharana, P.N. Shaw, and D. Markovich. (2006). Disruption of NaS1 sulfate transport function in mice leads to enhanced acetaminophen-induced hepatotoxicity. Hepatology 43: 1241-1247. 16729303
Li, H. and A.M. Pajor. (2003). Serines 260 and 288 are involved in sulfate transport by hNaSi-1. J. Biol. Chem. 278: 37204-37212. 12857732
Liu, L., M. Zacchia, X. Tian, L. Wan, A. Sakamoto, M. Yanagisawa, R.J. Alpern, and P.A. Preisig. (2010). Acid regulation of NaDC-1 requires a functional endothelin B receptor. Kidney Int 78: 895-904. 20703215
Mancusso R., Gregorio GG., Liu Q. and Wang DN. (2012). Structure and mechanism of a bacterial sodium-dependent dicarboxylate transporter. Nature. 491(7425):622-6. 23086149
Markovich, D. (2012). Sodium-sulfate/carboxylate cotransporters (SLC13). Curr Top Membr 70: 239-256. 23177988
Markovich, D., A. Romano, C. Storelli, and T. Verri. (2008). Functional and structural characterization of the zebrafish Na+-sulfate cotransporter 1 (NaS1) cDNA and gene (slc13a1). Physiol Genomics 34: 256-264. 18544660
Markovich, D., J. Forgo, G. Stange, J. Biber, and H. Murer. (1993). Expression cloning of rat renal Na+/SO42- cotransport. Proc. Natl. Acad. Sci. USA 90: 8073-8077. 7690140
Morris, M.E. and H. Murer. (2001). Molecular mechanisms in renal and intestinal sulfate (re)absorption. J. Membrane Biol. 181: 1-9. 11331932
Pajor, A.M. (1995). Sequence and functional characterization of a renal sodium/dicarboxylate cotransporter. J. Biol. Chem. 270: 5779-5785. 7890707
Pajor, A.M. (1999). Sodium-coupled transporters for Krebs Cycle intermediates. Annu. Rev. Physiol. 61: 663-682. 10099705
Pajor, A.M. (2000). Molecular properties of sodium/dicarboxylate cotransporters. J. Membrane. Biol. 175: 1-8. 10811962
Pajor, A.M. and N.N. Sun. (2010). Role of isoleucine-554 in lithium binding by the Na+/dicarboxylate cotransporter NaDC1. Biochemistry 49: 8937-8943. 20845974
Pajor, A.M., N. Sun, L. Bai, D. Markovich, and P. Sule. (1997). The substrate recognition domain in the Na+/dicarboxylate and Na+/sulfate cotransporters is located in the carboxy-terminal portion of the protein. Biochim. Biophys. Acta 1370: 98-106. 9518567
Pajor, A.M., N.N. Sun, A.D. Joshi, and K.M. Randolph. (2011). Transmembrane helix 7 in the Na+/dicarboxylate cotransporter 1 is an outer helix that contains residues critical for function. Biochim. Biophys. Acta. 1808: 1454-1461. 21073858
Pootakham, W., D. Gonzalez-Ballester, and A.R. Grossman. (2010). Identification and regulation of plasma membrane sulfate transporters in Chlamydomonas. Plant Physiol. 153: 1653-1668. 20498339
Pos, K.M., P. Dimroth, and M. Bott. (1998). The Escherichia coli citrate carrier CitT: a member of a novel eubacterial transporter family related to the 2-oxoglutarate/malate translocator from spinach chloroplasts. J. Bacteriol. 180: 4160-4165. 9696764
Prakash, S., G. Cooper, S. Singhi, and M.H. Saier, Jr. (2003). The ion transporter superfamily. Biochim. Biophys. Acta. 1618: 79-92. 14643936
Quentmeier, A., A. Holzenburg, F. Mayer, and G. Antranikian. (1987). Reevaluation of citrate lyase from Escherichia coli. Biochim. Biophys. Acta. 913: 60-65. 3555623
Rabus, R., D.L. Jack, D.J. Kelly, and M.H. Saier, Jr. (1999). TRAP transporters: an ancient family of periplasmic solute receptor-dependent secondary active transporters. Microbiology 145: 3431-3445. 10627041
Saier, M.H., Jr., B.H. Eng, S. Fard, J. Garg, D.A. Haggerty, W.J. Hutchinson, D.L. Jack, E.C. Lai, H.J. Liu, D.P. Nusinew, A.M. Omar, S.S. Pao, I.T. Paulsen, J.A. Quan, M. Sliwinski, T.-T. Tseng, S. Wachi, and G.B. Young. (1999). Phylogenetic characterization of novel transport protein families revealed by genome analyses. Biochim. Biophys. Acta 1422: 1-56. 10082980
Steffgen, J., B.C. Burckhardt, C. Langenberg, L. Kühne, G.A. Müller, G. Burckhardt, and N.A. Wolff. (1999). Expression cloning and characterization of a novel sodium-dicarboxylate cotransporter from winter flounder kidney. J. Biol. Chem. 274: 20191-20196. 10400635
Strickler MA., Hall JA., Gaiko O. and Pajor AM. (2009). Functional characterization of a Na(+)-coupled dicarboxylate transporter from Bacillus licheniformis. Biochim Biophys Acta. 1788(12):2489-96. 19840771
Taherpour, A. and A. Hashemi. (2013). Detection of OqxAB efflux pumps, OmpK35 and OmpK36 porins in extended-spectrum-β-lactamase-producing Klebsiella pneumoniae isolates from Iran. Hippokratia 17: 355-358. 25031516
Teramoto, H., T. Shirai, M. Inui, and H. Yukawa. (2008). Identification of a gene encoding a transporter essential for utilization of C4 dicarboxylates in Corynebacterium glutamicum. Appl. Environ. Microbiol. 74: 5290-5296. 18586971
Urbany, C. and H.E. Neuhaus. (2008). Citrate uptake into Pectobacterium atrosepticum is critical for bacterial virulence. Mol. Plant Microbe Interact. 21: 547-554. 18393614
Wada, M., A. Shimada, and T. Fujita. (2006). Functional characterization of Na+ -coupled citrate transporter NaC2/NaCT expressed in primary cultures of neurons from mouse cerebral cortex. Brain Res 1081: 92-100. 16516867
Wang, G., S.P. Kennedy, S. Fasiludeen, C. Rensing, and S. DasSarma. (2004). Arsenic resistance in Halobacterium sp. strain NRC-1 examined by using an improved gene knockout system. J. Bacteriol. 186: 3187-3194. 15126481
Weber, A., E. Menzlaff, B. Arbinger, M. Gutensohn, C. Eckerskorn, and U.-I. Flüge. (1995). The 2-oxoglutarate/malate translocator of chlorplast envelope membranes: molecular cloning of a transporter containing a 12-helix motif and expression of the functional protein in yeast cells. Biochemistry 34: 2621-2627. 7873543
Yodoya, E., M. Wada, A. Shimada, H. Katsukawa, N. Okada, A. Yamamoto, V. Ganapathy, and T. Fujita. (2006). Functional and molecular identification of sodium-coupled dicarboxylate transporters in rat primary cultured cerebrocortical astrocytes and neurons. J. Neurochem. 97: 162-173. 16524379
Youn, J.W., E. Jolkver, R. Krämer, K. Marin, and V.F. Wendisch. (2008). Identification and characterization of the dicarboxylate uptake system DccT in Corynebacterium glutamicum. J. Bacteriol. 190: 6458-6466. 18658264