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). 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: Anion^2- (out) + nM⁺ [Na⁺ or H⁺] (out) → Anion^2- (in) + nM⁺ (in).
This family belongs to the IT Superfamily.
References:
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.
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.
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.
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.
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.
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.
Markovich, D., J. Forgo, G. Stange, J. Biber, and H. Murer. (1993). Expression cloning of rat renal Na⁺/SO₄^2- cotransport. Proc. Natl. Acad. Sci. USA 90: 8073-8077.
Morris, M.E. and H. Murer. (2001). Molecular mechanisms in renal and intestinal sulfate (re)absorption. J. Membrane Biol. 181: 1-9.
Pajor, A.M. (1995). Sequence and functional characterization of a renal sodium/dicarboxylate cotransporter. J. Biol. Chem. 270: 5779-5785.
Pajor, A.M. (1999). Sodium-coupled transporters for Krebs Cycle intermediates. Annu. Rev. Physiol. 61: 663-682.
Pajor, A.M. (2000). Molecular properties of sodium/dicarboxylate cotransporters. J. Membrane. Biol. 175: 1-8.
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.
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.
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.
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.
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.
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.
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.
Examples:
TC#	Name	Organismal Type	Example
2.A.47.1.1	Intestinal low affinity (sodium)₃: dicarboxylate (succinate, fumarate, malate, α-heteroglutarate, glutarate, citrate-H⁺) cotransporter (NaDC-1)	Animals	NaDC-1 of Rattus norvegicus

2.A.47.1.2	Renal sodium:sulfate cotransporter (Ssc) (NaS₁-1) (also transports thiosulfate and selenate) (Li and Pajor, 2003)	Animals	Ssc of Rattus norvegicus

2.A.47.1.3	Renal sodium:dicarboxylate (citrate, succinate, α-ketoglutarate, oxaloacetate, L- and D-glutamate, L- and D-aspartate) cotransporter, SDCT1	Animals	SDCT1 of Rattus norvegicus

2.A.47.1.4	High affinity decarboxylate:(Na⁺)₃ cotransporter (NaDC-3) (substrate range similar to that of NDC-1 except that tricarboxylates are transported with very low affinity)	Animals	NaDC-3 of Rattus norvegicus

2.A.47.1.5	Basolateral Na⁺: di- and tricarboxylate (succinate cis-aconitate, citrate, etc.) cotransporter, fNaDC-3	Animals	*fNaDC-3 of Pseudopleuronectes americanus* (the winter flounder)**

2.A.47.1.6	Malate:Na⁺ symporter	Plants	Malate:Na⁺ symporter of Arabidopsis thaliana

2.A.47.1.7	Low affinity dicarboxylate:Na⁺ symporter, NaDC1 (INDY1) (relative affinities: succinate > fumarate > α-ketoglutarate > malate > lactate > maleate) (Fei et al., 2003)	Animals	NaDC1 of Caenorhabditis elegans

2.a.47.1.8	High affinity dicarboxylate:Na⁺ symporter, NaDC2 (INDY2) (relative affinities: fumarate > malate > α-ketoglutarate > maleate > succinate > lactate) (Fei et al., 2003)	Animals	NaDC2 of Caenorhabditis elegans

2.A.47.1.9	Na⁺-coupled citrate transporter (NaCT) (also may transport dicarboxylates and other tricarboxylates with lower affinity) (Inoue et al., 2002)	Animals	NaCT of Homo sapiens

2.A.47.2.1	Inorganic phosphate transporter, Pho87	Yeast	Pho87 of Saccharomyces cerevisiae

2.A.47.3.1	2-oxoglutarate:malate antiporter (SodiTl)	Plant chloroplasts	SodiTl of Spinacia oleracea

2.A.47.3.2	Citrate:succinate antiporter	Bacteria	CitT of E. coli

2.A.47.3.3	Probable tartrate:succinate antiporter	Bacteria	YgiE of E. coli

2.A.47.4.1	Sulfur-deprivation response protein	Cyanobacteria	SdrP of Synechocystis

2.A.47.4.2	Antimonite resistance protein (inducible by both arsenite and antimonite although arsenite resistance was not detected)	Archaea	*ArsB of Halobacterium* spNRC-1 (AAG20642)**

2.A.47.5.1	Hypothetical Na⁺ cotransporter, Orfl	Archaea	Orfl of Methanococcus jannaschii