2.A.53 The Sulfate Permease (SulP) Family The SulP family is a large and ubiquitous family with over 100 sequenced members derived from bacteria, fungi, plants and animals. Many organisms including Bacillus subtilis, Synechocystis sp, Saccharomyces cerevisiae, Arabidopsis thaliana and Caenorhabditis elegans possess multiple SulP family paralogues. Many of these proteins are functionally characterized, and all are inorganic anion uptake transporters or anion:anion exchange transporters. Some transport their substrate(s) with high affinities, while others transport it or them with relatively low affinities. Many function by SO₄^2-:H⁺ symport, but SO₄^2-:HCO₃^-, or more generally, anion:anion antiport has been reported for several homologues. For example the mouse homologue, Slc26a6 (TC #2.A.53.2.7), can transport sulfate, formate, oxalate, chloride and bicarbonate, exchanging any one of these anions for another (Jiang et al., 2002). The bacterial proteins vary in size from 434 residues to 573 residues with only a few exceptions. The eukaryotic proteins vary in size from 611 residues to 893 residues with a few exceptions. Thus, the eukaryotic proteins are usually larger than the prokaryotic homologues. These proteins exhibit 10-13 putative transmembrane α-helical spanners (TMSs) depending on the protein. The generalized transport reactions catalyzed by SulP family proteins are: (1) SO₄^2- (out) + nH⁺ (out) → SO₄^2- (in) + nH⁺ (in). (2) SO₄^2- (out) + nHCO₃^- (in) SO₄^2- (in) + nHCO₃^- (out). (3) I^- and other anions (out) I^- and other anions (in)
References:
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Hastbacka, J., A. De La Chapelle, M.M. Mahtani, G. Clines, M.P. Reeve-Daly, M. Daly, B.A. Hamilton, K. Kusumi, B. Trivedi, A. Weaver, A. Coloma, M. Lovett, A. Buckler, I. Kaitila, and E.S. Landers. (1994). The diastrophic dysplasia gene encodes a novel sulfate transporter: positional cloning by fine-structure linkage disequilibrium mapping. Cell 78: 1073-1087.
Hastbacka, J., A. Superti-Furga, W.R. Wilcox, D.L. Rimoin, D.H. Cohn, and E.S. Landers. (1996) Atelosteogenesis type II is caused by mutations in the diastrophic dysplasia sulfate-transporter gene (DTDST): evidence for a phenotypic series involving three chondrodysplasias. Am. J. Hum. Genet. 58: 255-262.
Jiang, Z., I.I. Grichtchenko, W.F. Boron, and P.S. Aronson. (2002). Specificity of anion exhange mediated by mouse Slc26a6. J. Biol. Chem. 277: 33963-33967.
Ketter, J.S., G. Jarai, Y.H. Fu, and G.A. Marzluf. (1991). Nucleotide sequence, messenger RNA stability, and DNA recognition elements of cys-14, the structural gene for sulfate permease II in Neurospora crassa. J. Biochem. 30: 1780-1787.
Liberman, M.C., J. Gao, D.Z.Z. He, X. Wu, S. Jia, and J. Zuo. (2002). Prestin is required for electromotility of the outer hair cell and for the cochlear amplifier. Nature 419: 300-304.
Lohi, H., M. Kujala, S. Mäkela, E. Lehtonen, M. Kestilä, U. Saarialho-Kere, D. Markovich, and J. Kere. (2002). Functional characterization of three novel tissue-specific anion exchangers SLC26A7, -A8, and -A9. J. Biol. Chem. 277: 14246-14254.
Ludwig, J., D. Oliver, G. Frank, N. Klöcker, A.W. Gummer, and B. Fakler. (2001). Reciprocal electromechanical properties of rat prestin: the motor molecule from rat outer hair cells. Proc. Natl. Acad. Sci. USA 98: 4178-4183.
Melvin, J.E., K. Park, L. Richardson, P.J. Schultheis, and G.E. Shull. (1999). Mouse down-regulated in adenoma (DRA) is an intestinal Cl^-/HCO₃^- exchanger and is up-regulated in colon of mice lacking the NHE3 Na⁺/H⁺ exchanger. J. Biol. Chem. 274: 22855-22861.
Oliver, D., D.Z.Z. He, N. Klöcker, J. Ludwig, U. Schulte, S. Waldegger, J.P. Ruppersberg, P. Dallos, and B. Fakler. (2001). Intracellular anions as the voltage sensor of prestin, the outer hair cell motor protein. Science 292: 2340-2343.
Royaux, I.E., S.M. Wall, L.P. Karniski, L.A. Everett, K. Suzuki, M.A. Knepper, and E.D. Green. (2001). Pendrin, encoded by the Pendred syndrome gene, resides in the apical region of renal intercalated cells and mediates bicarbonate secretion. Proc. Natl. Acad. Sci. USA 98: 4221-4226.
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.
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Examples:
TC#	Name	Organismal Type	Example
2.A.53.1.1	High-affinity sulfate permease	Yeast	Sulfate permease of Saccharomyces cerevisiae

2.A.53.1.2	Sulfate permease II	Fungi	Sulfate permease of Neurospora crassa

2.A.53.1.3	High-affinity sulfate:H⁺ symporter 1, Sut1	Plants	High-affinity sulfate transporter 1 of Stylosanthes hamata

2.A.53.1.4	Low-affinity sulfate:H⁺ symporter, Sut3	Plants	Low-affinity sulfate transporter3, Sut3 of Stylosanthes hamata

2.A.53.1.5	Early Nodulin 70, Nod70	Plants	Nod70 of Glycine max

2.A.53.2.1	Sulfate/anion transporter (diastrophic dysplasia protein) (SLC26A2)	Animals	Sulfate/anion transporter of Homo sapiens

2.A.53.2.2	Canicular sulfate:HCO₃^- antiporter	Animals	Sulfate transporter 1 of Rattus norvegicus

2.A.53.2.3	Intestinal down-regulated in adenoma (DRA) protein; HCO₃^-/Cl^- antiporter	Animals	DRA of Mus musculus

2.A.53.2.4	Pendrin (Pendred) syndrome (hereditary deafness) anion transporter (Na⁺-independent). Anions transported: iodide (thyroid gland; apical membrane of follicular epithelium); bicarbonate (kidney; apical membrane of intercalated cells of the cortical collecting duct), chloride, formate, etc. Pendrin probably catalyzes uniport and anion/anion antiport (SLC26A4).	Animals	Pendrin of Mus musculus

2.A.53.2.5	Prestin, the outer hair cell voltage-sensitive motor protein (voltage sensitivity depends on intracellular Cl^- and HCO₃^- which may bind to prestin.)(A transport function is not established.)	Animals	Prestin of Mus musculus

2.A.53.2.6	Kidney chloride/sulfate/oxalate permease, SLC26A7	Animals	*Anion transporter of Homo sapiens* SLC26A7**

2.A.53.2.7	The mouse Slc26a6 anion exchanger (transports sulfate, formate, oxalate, chloride and bicarbonate in antiport with any one of these anions) (Jiang et al., 2002)	Animals	Slc26a6 of Mus musculus

2.A.53.3.1	Sulfate permease	Bacteria	Sulfate permease of Yersinia enterocolitica

2.A.53.4.1	Sulfate transporter	Bacteria	Sulfate transporter of Synechocystis sp.