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2.A.21 The Solute:Sodium Symporter (SSS) Family

Members of the SSS family catalyze solute:Na+ symport. The solutes transported may be sugars, amino acids, organo cations such as choline, nucleosides, inositols, vitamins, urea or anions, depending on the system. Members of the SSS family have been identified in bacteria, archaea and animals, and all functionally well-characterized members normally catalyze solute uptake via Na+ symport. The human placental multivitamin symporter cotransports an anionic vitamin with two Na+. In the rabbit Na+:D-glucose cotransporter, SGLT1, the glucose translocation pathway probably involves TMSs 10-13, and the binding site for the inhibitor, phlorizin, involves loop 13 (residues 604-610). Cation binding in the N-terminal domain may induce transport-related conformational changes. A conserved tyrosine in the first transmembrane segment of solute:sodium symporters is involved in Na+-coupled substrate co-transport (Mazier et al., 2011).  Mechanistic aspects of Na+ binding sites in LeuT-like fold symporters has been discussed in detail (Perez and Ziegler 2013). The mechanisms of LacY (TC# 2.A.1.5.1) and vSGLT (TC# 2.A.21.3.1) have been compared and discussed (Abramson and Wright 2021).

In the human homologue (hSGLT1), H+ can replace Na+, but the apparent affinity for glucose reduces 20x from 0.3 mM to 6 mM. The apparent affinity for H+ is 6 μM, 1000x higher than for Na+ (6 mM). The transport stoichiometry is 1 glucose:2 Na+ or H+. If Asp204 is replaced by glutamate (D204E), the apparent affinity for H+ increases >20x with no change in apparent Na+ affinity. The D204N or D204C mutation promotes phlorizin-sensitive H+ currents that are 10x greater than Na+ currents, and the glucose:H+ stoichiometry is then as great as 1:145. The mutant system thus behaves as a glucose-gated H+ channel.  Sodium channels Na(v) 1.1, 1.2, and 1.6 expressed in stably transfected HEK293 cells and brain tissues from mice, rats, and humans have beeen measured.  Na(v) expression ranking was Na(v) 1.2 >> Na(v) 1.1 > Na(v) 1.6, with the human brain expressing much lower concentrations overall compared to rodent brain (Kwan et al. 2024).

Proteins of the SSS vary in size from about 400 residues to about 700 residues and probably possess thirteen to fifteen putative transmembrane helical spanners (TMSs). They generally share a core of 13 TMSs, but different members of the family may have different numbers of TMSs. A 13 TMS topology with a periplasmic N-terminus and a cytoplasmic C-terminus has been experimentally determined for the proline:Na+ symporter, PutP, of E. coli. Residues important for substrate and Na+ binding in PutP are found in TMSs 2, 7 and 9 as well as adjacent loops (Jung, 2002). A 14 TMS topology with periplasmic N- and C-termini has been established for the V. parahaemolyticus SglT carrier. SglT transports sugar:Na with a 1:1 stoichiometry. However, MctP of Rhizobium leguminosarum may take up monocarboxylates via an H+ symport mechanism as a dependency on Na+ could not be demonstrated and uptake was strongly inhibited by 10 μM CCCP.

Faham et al., 2008 reported the crystal structure of a member of the solute sodium symporters (SSS), the Vibrio parahaemolyticus sodium/galactose symporter (vSGLT). The approximately 3.0 angstrom structure contains 14 transmembrane (TM) helices in an inward-facing conformation with a core structure of inverted repeats of 5 TM helices (TM2 to TM6 and TM7 to TM11). Galactose is bound in the center of the core, occluded from the outside solutions by hydrophobic residues. The architecture of the core is similar to that of the leucine transporter (LeuT) (TC#2.A.22.4.2) from the NSS family. Modeling the outward-facing conformation based on the LeuT structure, in conjunction with biophysical data, provided insight into structural rearrangements for active transport (Faham et al., 2008).

Some bacterial sensor kinases (2.A.21.9.1 and 2.A.22.9.2) have N-terminal, 12 TMS, sensor domains that regulate the C-terminal kinase domains. The latter are homologous to the kinase domain of NtrB (Pao and Saier, 1995). The N-terminal sensor domains are homologous, but distantly related to members of the SSS. The closest homologues are PutP of E. coli (2.A.21.2.1) and PanF of E. coli (2.A.21.1.1). Homologous regulatory domains are found in Agrobacterium, Mesorhizobium, Sinorhizobium, Vibrio cholera and Bacillus species. While it is clear that these domains function as sensors, it is not known if they also transport the small molecules they sense.

The generalized transport reaction catalyzed by the members of this family is:

solute (out) + nNa+ (out) → solute (in) + nNa+ (in)

This family belongs to the: APC Superfamily.

References associated with 2.A.21 family:

Abramson, J. and E.M. Wright. (2021). Function Trumps Form in Two Sugar Symporters, and. Int J Mol Sci 22:. 33808202
Ali, M.U., G.B.J. Mancini, D. Fitzpatrick-Lewis, K.A. Connelly, E. O''Meara, S. Zieroth, and D. Sherifali. (2024). The effectiveness of sodium-glucose co-transporter 2 inhibitors on cardiorenal outcomes: an updated systematic review and meta-analysis. Cardiovasc Diabetol 23: 72. 38360604
Althoff, T., H. Hentschel, J. Luig, H. Schütz, M. Kasch, and R.K. Kinne. (2006). Na+-D-glucose cotransporter in the kidney of Squalus acanthias: molecular identification and intrarenal distribution. Am. J. Physiol. Regul Integr Comp Physiol 290: R1094-1104. 16306165
Althoff, T., H. Hentschel, J. Luig, H. Schütz, M. Kasch, and R.K. Kinne. (2007). Na+ -D-glucose cotransporter in the kidney of Leucoraja erinacea: molecular identification and intrarenal distribution. Am. J. Physiol. Regul Integr Comp Physiol 292: R2391-2399. 17322119
Anba-Mondoloni, J., S. Chaillou, M. Zagorec, and M.C. Champomier-Vergès. (2013). Catabolism of N-acetylneuraminic acid, a fitness function of the food-borne lactic acid bacterium Lactobacillus sakei, involves two newly characterized proteins. Appl. Environ. Microbiol. 79: 2012-2018. 23335758
Aouameur, R., S. Da Cal, P. Bissonnette, M.J. Coady, and J.Y. Lapointe. (2007). SMIT2 mediates all myo-inositol uptake in apical membranes of rat small intestine. Am. J. Physiol. Gastrointest. Liver. Physiol. 293(6):G1300-G1307.
Barta, T., W. Sandtner, J. Wachlmayr, C. Hannesschlaeger, A. Ebert, A. Speletz, and A. Horner. (2022). Modeling of SGLT1 in Reconstituted Systems Reveals Apparent Ion-Dependencies of Glucose Uptake and Strengthens the Notion of Water-Permeable Apo States. Front Physiol 13: 874472. 35784872
Barwick, K.E., J. Wright, S. Al-Turki, M.M. McEntagart, A. Nair, B. Chioza, A. Al-Memar, H. Modarres, M.M. Reilly, K.J. Dick, A.M. Ruggiero, R.D. Blakely, M.E. Hurles, and A.H. Crosby. (2012). Defective presynaptic choline transport underlies hereditary motor neuropathy. Am J Hum Genet 91: 1103-1107. 23141292
Bernal Barquero, C.E., M. Martín, R.C. Geysels, V. Peyret, P. Papendieck, A.M. Masini-Repiso, A.E. Chiesa, and J.P. Nicola. (2022). An Intramolecular Ionic Interaction Linking Defective Sodium/Iodide Symporter Transport to the Plasma Membrane and Dyshormonogenic Congenital Hypothyroidism. Thyroid 32: 19-27. 34726525
Borghese, R. and D. Zannoni. (2010). Acetate permease (ActP) Is responsible for tellurite (TeO32-) uptake and resistance in cells of the facultative phototroph Rhodobacter capsulatus. Appl. Environ. Microbiol. 76: 942-944. 19966028
Borghese, R., L. Canducci, F. Musiani, M. Cappelletti, S. Ciurli, R.J. Turner, and D. Zannoni. (2016). On the role of a specific insert in acetate permeases (ActP) for tellurite uptake in bacteria: Functional and structural studies. J Inorg Biochem 163: 103-109. 27421695
Borghese, R., S. Cicerano, and D. Zannoni. (2011). Fructose increases the resistance of Rhodobacter capsulatus to the toxic oxyanion tellurite through repression of acetate permease (ActP). Antonie Van Leeuwenhoek 100: 655-658. 21735076
Bracher, S., C.C. Schmidt, S.I. Dittmer, and H. Jung. (2016). Core Transmembrane Domain 6 Plays a Pivotal Role in the Transport Cycle of the Sodium/Proline Symporter PutP. J. Biol. Chem. 291: 26208-26215. 27793991
Bracher, S., K. Guérin, Y. Polyhach, G. Jeschke, S. Dittmer, S. Frey, M. Böhm, and H. Jung. (2016). Glu311 in External Loop 4 of the Sodium/Proline Transporter PutP is Crucial for External Gate Closure. J. Biol. Chem. [Epub: Ahead of Print] 26728461
Brosch, P.K., T. Korsa, D. Taban, P. Eiring, S. Hildebrand, J. Neubauer, H. Zimmermann, M. Sauer, R. Shirakashi, C.S. Djuzenova, D. Sisario, and V.L. Sukhorukov. (2022). Glucose and Inositol Transporters, SLC5A1 and SLC5A3, in Glioblastoma Cell Migration. Cancers (Basel) 14:. 36497276
Brown, E., S.P. Rajeev, D.J. Cuthbertson, and J.P.H. Wilding. (2019). A review of the mechanism of action, metabolic profile and haemodynamic effects of sodium-glucose co-transporter-2 inhibitors. Diabetes Obes Metab 21Suppl2: 9-18. 31081592
Chakrabarti, M., L.M. Amzel, and A.Y. Lau. (2023). Sodium/Iodide Symporter Metastable Intermediates Provide Insights into Conformational Transition between Principal Thermodynamic States. J Phys Chem B 127: 1540-1551. 36758032
Chen ML., Yi L., Jin X., Xie Q., Zhang T., Zhou X., Chang H., Fu YJ., Zhu JD., Zhang QY. and Mi MT. (2013). Absorption of resveratrol by vascular endothelial cells through passive diffusion and an SGLT1-mediated pathway. J Nutr Biochem. 24(11):1823-9. 23927891
Chen, X., H. Shen, H. Liu, L. Tan, and N. Zhang. (2024). CMTM 6 promotes the development of thyroid cancer by inhibiting NIS activity through activating the MAPK signaling pathway. Funct Integr Genomics 24: 10. 38221563
Coady, M.J., B. Wallendorff, D.G. Gagnon, and J.-Y. Lapointe. (2002). Identification of a novel Na+/myo-inositol cotransporter. J. Biol. Chem. 277: 35219-35224. 12133831
Darrouzet, E., S. Lindenthal, D. Marcellin, J.L. Pellequer, and T. Pourcher. (2014). The sodium/iodide symporter: State of the art of its molecular characterization. Biochim. Biophys. Acta. 1838: 244-253. 23988430
de Carvalho, F.D. and M. Quick. (2011). Surprising substrate versatility in SLC5A6: Na+-coupled I- transport by the human Na+/multivitamin transporter (hSMVT). J. Biol. Chem. 286: 131-137. 20980265
De la Vieja, A., M.D. Reed, C.S. Ginter, and N. Carrasco. (2007). Amino acid residues in transmembrane segment IX of the Na+/I- symporter play a role in its Na+ dependence and are critical for transport activity. J. Biol. Chem. 282: 25290-25298. 17606623
Dohán, O., C. Portulano, C. Basquin, A. Reyna-Neyra, L.M. Amzel, and N. Carrasco. (2007). The Na+/I symporter (NIS) mediates electroneutral active transport of the environmental pollutant perchlorate. Proc. Natl. Acad. Sci. U.S.A. 104: 20250-20255. 18077370
Dus, M., M. Ai, and G.S. Suh. (2013). Taste-independent nutrient selection is mediated by a brain-specific Na+ /solute co-transporter in Drosophila. Nat Neurosci 16: 526-528. 23542692
Eleftheriadou, A.M., S. Mehl, K. Renko, R.H. Kasim, J.A. Schaefer, W.B. Minich, and L. Schomburg. (2020). Re-visiting autoimmunity to sodium-iodide symporter and pendrin in thyroid disease. Eur J Endocrinol 183: 571-580. 33055303
Elías, A., W. Díaz-Vásquez, M.J. Abarca-Lagunas, T.G. Chasteen, F. Arenas, and C.C. Vásquez. (2015). The ActP acetate transporter acts prior to the PitA phosphate carrier in tellurite uptake by Escherichia coli. Microbiol Res 177: 15-21. 26211961
Erokhova, L., A. Horner, N. Ollinger, C. Siligan, and P. Pohl. (2016). The Sodium Glucose Cotransporter SGLT1 Is an Extremely Efficient Facilitator of Passive Water Transport. J. Biol. Chem. 291: 9712-9720. 26945065
Eskandari, S., D.D.F. Loo, G. Dai, O. Levy, E.M. Wright, and N. Carrasco. (1997). Thyroid Na+/I- symporter: mechanism, stoichiometry, and specificity. J. Biol. Chem. 272: 27230-27238. 9341168
Faham, S., A. Watanabe, G.M. Besserer, D. Cascio, A. Specht, B.A. Hirayama, E.M. Wright, and J. Abramson. (2008). The crystal structure of a sodium galactose transporter reveals mechanistic insights into Na+/sugar symport. Science 321: 810-814. 18599740
Feng, F., L. Yehia, Y. Ni, Y.S. Chang, S.M. Jhiang, and C. Eng. (2018). A Nonpump Function of Sodium Iodide Symporter in Thyroid Cancer via Cross-talk with PTEN Signaling. Cancer Res 78: 6121-6133. 30217930
Ferté, L., A. Marino, S. Battault, L. Bultot, A. Van Steenbergen, A. Bol, J. Cumps, A. Ginion, H. Koepsell, L. Dumoutier, L. Hue, S. Horman, L. Bertrand, and C. Beauloye. (2021). New insight in understanding the contribution of SGLT1 in cardiac glucose uptake: evidence for a truncated form in mice and humans. Am. J. Physiol. Heart Circ Physiol 320: H838-H853. 33416451
Fisher, D.J., R.E. Fernández, N.E. Adams, and A.T. Maurelli. (2012). Uptake of biotin by Chlamydia Spp. through the use of a bacterial transporter (BioY) and a host-cell transporter (SMVT). PLoS One 7: e46052. 23029384
Frank, H., N. Gröger, M. Diener, C. Becker, T. Braun, and T. Boettger. (2008). Lactaturia and loss of sodium-dependent lactate uptake in the colon of SLC5A8-deficient mice. J. Biol. Chem. 283: 24729-24737. 18562324
Gimenez, R., M.F. Nuñez, J. Badia, J. Aguilar, and L. Baldoma. (2003). The gene yjcG, cotranscribed with the gene acs, encodes an acetate permease in Escherichia coli. J. Bacteriol. 185: 6448-6455. 14563880
Gopal, E., S. Miyauchi, P.M. Martin, S. Ananth, P. Roon, S.B. Smith, and V. Ganapathy. (2007). Transport of nicotinate and structurally related compounds by human SMCT1 (SLC5A8) and its relevance to drug transport in the mammalian intestinal tract. Pharm Res 24: 575-584. 17245649
Gopal, E., Y.J. Fei, M. Sugawara, S. Miyauchi, L. Zhuang, P. Martin, S.B. Smith, P.D. Prasad, and V. Ganapathy. (2004). Expression of slc5a8 in kidney and its role in Na+-coupled transport of lactate. J. Biol. Chem. 279: 44522-44532. 15322102
Guo, Y., Z. Ran, Y. Zhang, Z. Song, L. Wang, L. Yao, M. Zhang, J. Xin, and X. Mao. (2020). Marein ameliorates diabetic nephropathy by inhibiting renal sodium glucose transporter 2 and activating the AMPK signaling pathway in db/db mice and high glucose-treated HK-2 cells. Biomed Pharmacother 131: 110684. 33152903
Haga, T. (2014). Molecular properties of the high-affinity choline transporter CHT1. J Biochem 156: 181-194. 25073461
Halestrap, A.P. (2013). Monocarboxylic acid transport. Compr Physiol 3: 1611-1643. 24265240
Holling, T., S. Nampoothiri, B. Tarhan, P.E. Schneeberger, K.P. Vinayan, D. Yesodharan, A.G. Roy, P. Radhakrishnan, M. Alawi, L. Rhodes, K.M. Girisha, P.B. Kang, and K. Kutsche. (2022). Novel biallelic variants expand the SLC5A6-related phenotypic spectrum. Eur J Hum Genet. [Epub: Ahead of Print] 35013551
Hopkins AP., Hawkhead JA. and Thomas GH. (2013). Transport and catabolism of the sialic acids N-glycolylneuraminic acid and 3-keto-3-deoxy-D-glycero-D-galactonononic acid by Escherichia coli K-12. FEMS Microbiol Lett. 347(1):14-22. 23848303
Hosie, A.H., D. Allaway, and P.S. Poole. (2002). A monocarboxylate permease of Rhizobium leguminosarum is the first member of a new subfamily of transporters. J. Bacteriol. 184: 5436-5448. 12218032
Hoşnut, F.&.#.2.1.4.;., A.R. Janecke, G. Şahin, G.F. Vogel, N.G. Lafcı, P. Bichler, T. Müller, L.A. Huber, T. Valovka, and A.&.#.2.2.0.;. Aksu. (2023). Variants in Turkish Patients with Congenital Glucose-Galactose Malabsorption. Genes (Basel) 14:. 37510265
Huc-Brandt, S., D. Marcellin, F. Graslin, O. Averseng, L. Bellanger, P. Hivin, E. Quemeneur, C. Basquin, V. Navarro, T. Pourcher, and E. Darrouzet. (2011). Characterisation of the purified human sodium/iodide symporter reveals that the protein is mainly present in a dimeric form and permits the detailed study of a native C-terminal fragment. Biochim. Biophys. Acta. 1808: 65-77. 20797386
Jackowski, S. and J.H. Alix. (1990). Cloning, sequence, and expression of the pantothenate permease (panF) gene of Escherichia coli. J. Bacteriol. 172: 3842-3848. 2193919
Jiang, X., D.D. Loo, B.A. Hirayama, and E.M. Wright. (2012). The importance of being aromatic: π interactions in sodium symporters. Biochemistry 51: 9480-9487. 23116249
Johnson, D.A., S.G. Tetu, K. Phillippy, J. Chen, Q. Ren, and I.T. Paulsen. (2008). High-throughput phenotypic characterization of Pseudomonas aeruginosa membrane transport genes. PLoS Genet 4: e1000211. 18833300
Jung, H. (2002). The sodium/substrate symporter family: structural and functional features. FEBS Lett. 529: 73-77. 12354616
Jung, H., D. Hilger, and M. Raba. (2012). The Na+/L-proline transporter PutP. Front Biosci 17: 745-759. 22201772
Jung, H., R. Rübenhagen, S. Tebbe, K. Leifker, N. Tholema, M. Quick, and R. Schmid. (1998). Topology of the Na+/proline transporter of Escherichia coli. J. Biol. Chem. 273: 26400-26407. 9756872
Kanbay, M., M.C. Bulbul, S. Copur, B. Afsar, A.A. Sag, D. Siriopol, M. Kuwabara, S. Badarau, A. Covic, and A. Ortiz. (2021). Therapeutic implications of shared mechanisms in non-alcoholic fatty liver disease and chronic kidney disease. J Nephrol 34: 649-659. 32440840
Kashiwagi, K. and K. Igarashi. (2011). Identification and assays of polyamine transport systems in Escherichia coli and Saccharomyces cerevisiae. Methods Mol Biol 720: 295-308. 21318881
Kojima, S., A. Bohner, and N. von Wirén. (2006). Molecular mechanisms of urea transport in plants. J. Membr. Biol. 212: 83-91. 17264988
Kojima, S., A. Bohner, B. Gassert, L. Yuan, and N. von Wirén. (2007). AtDUR3 represents the major transporter for high-affinity urea transport across the plasma membrane of nitrogen-deficient Arabidopsis roots. Plant J. 52: 30-40. 17672841
Korycinski M., Albrecht R., Ursinus A., Hartmann MD., Coles M., Martin J., Dunin-Horkawicz S. and Lupas AN. (2015). STAC--A New Domain Associated with Transmembrane Solute Transport and Two-Component Signal Transduction Systems. J Mol Biol. 427(20):3327-39. 26321252
Kumar, A., M.A. Faiq, V. Pareek, K. Raza, R.K. Narayan, P. Prasoon, P. Kumar, M. Kulandhasamy, C. Kumari, K. Kant, H.N. Singh, R. Qadri, S.N. Pandey, and S. Kumar. (2020). Relevance of SARS-CoV-2 related factors ACE2 and TMPRSS2 expressions in gastrointestinal tissue with pathogenesis of digestive symptoms, diabetes-associated mortality, and disease recurrence in COVID-19 patients. Med Hypotheses 144: 110271. 33254575
Kwan, R., P. Das, N. Gerrebos, J. Li, X.Y. Wang, G. DeBoer, V. Emnacen-Pankhurst, S. Lin, R. Feng, S. Goodchild, and L.E. Sojo. (2024). Development and application of a multiple reaction monitoring method for the simultaneous quantification of sodium channels Na 1.1, Na 1.2, and Na 1.6 in solubilized membrane proteins from stable HEK293 cell lines, rodents, and human brain tissues. Rapid Commun Mass Spectrom 38: e9672. 38211346
Lechner, M.G. and G.A. Brent. (2024). A New Twist on a Classic: Enhancing Radioiodine Uptake in Advanced Thyroid Cancer. Clin Cancer Res. [Epub: Ahead of Print] 38197869
Li, S., J. Liu, Z. Li, L. Wang, W. Gao, Z. Zhang, and C. Guo. (2020). Sodium-dependent glucose transporter 1 and glucose transporter 2 mediate intestinal transport of quercetrin in Caco-2 cells. Food Nutr Res 64:. 32612490
Li, W., J.P. Nicola, L.M. Amzel, and N. Carrasco. (2013). Asn441 plays a key role in folding and function of the Na+/I- symporter (NIS). FASEB J. 27: 3229-3238. 23650190
Li, Z. (2019). Further insights into cardiovascular outcomes in diabetic and non-diabetic states: inhibition of sodium-glucose co-transports. Cardiovasc Endocrinol Metab 8: 90-95. 31942549
Liang, H., X. Ge, M. Ren, L. Zhang, D. Xia, J. Ke, and L. Pan. (2021). Molecular characterization and nutritional regulation of sodium-dependent glucose cotransporter 1 (Sglt1) in blunt snout bream (Megalobrama amblycephala). Sci Rep 11: 13962. 34234240
Liang, X., F. Yan, Y. Gao, M. Xiong, H. Wang, K. Onxayvieng, R. Tang, L. Li, X. Zhang, W. Chi, M. Piria, M.M. Fuka, A. Gavrilović, and D. Li. (2020). Sugar transporter genes in grass carp (Ctenopharyngodon idellus): molecular cloning, characterization, and expression in response to different stocking densities. Fish Physiol Biochem. [Epub: Ahead of Print] 32062828
Liu GW., Sun AL., Li DQ., Athman A., Gilliham M. and Liu LH. (2015). Molecular identification and functional analysis of a maize (Zea mays) DUR3 homolog that transports urea with high affinity. Planta. 241(4):861-74. 25522795
Liu, T., B. Lo, P. Speight, and M. Silverman. (2008). Transmembrane IV of the high-affinity sodium-glucose cotransporter participates in sugar binding. Am. J. Physiol. Cell Physiol. 295: C64-72. 18448629
Llorente-Esteban, A., R.W. Manville, A. Reyna-Neyra, G.W. Abbott, L.M. Amzel, and N. Carrasco. (2020). Allosteric regulation of mammalian Na/I symporter activity by perchlorate. Nat Struct Mol Biol 27: 533-539. 32451489
Ma, Y., X. Chen, T. Diao, Y. Leng, X. Lai, and X. Wei. (2022). The Effect of Ferulic Acid-Grafted Chitosan (FA-g-CS) on the Transmembrane Transport of Anthocyanins by and. Foods 11:. 37431047
Martín, M. and J.P. Nicola. (2021). Impact of the Mutational Landscape of the Sodium/Iodide Symporter in Congenital Hypothyroidism. Thyroid 31: 1776-1785. 34514854
Mayer, F.L., D. Wilson, I.D. Jacobsen, P. Miramón, K. Große, and B. Hube. (2012). The Novel Candida albicans Transporter Dur31 Is a Multi-Stage Pathogenicity Factor. PLoS Pathog 8: e1002592. 22438810
Mazier, S., M. Quick, and L. Shi. (2011). Conserved tyrosine in the first transmembrane segment of solute:sodium symporters is involved in Na+-coupled substrate co-transport. J. Biol. Chem. 286: 29347-29355. 21705334
Mérigout, P., M. Lelandais, F. Bitton, J.P. Renou, X. Briand, C. Meyer, and F. Daniel-Vedele. (2008). Physiological and transcriptomic aspects of urea uptake and assimilation in Arabidopsis plants. Plant Physiol. 147: 1225-1238. 18508958
Miyauchi S., Gopal E., Babu E., Srinivas SR., Kubo Y., Umapathy NS., Thakkar SV., Ganapathy V. and Prasad PD. (2010). Sodium-coupled electrogenic transport of pyroglutamate (5-oxoproline) via SLC5A8, a monocarboxylate transporter. Biochim Biophys Acta. 1798(6):1164-71. 20211600
Miyauchi, S., E. Gopal, Y.-J. Fei, and V. Ganapathy. (2004). Functional identification of SLC5A8, a tumor suppressor down-regulated in colon cancer, as a Na+-coupled transporter for short-chain fatty acids. J. Biol. Chem. 279: 13293-13296. 14966140
Moses, S., T. Sinner, A. Zaprasis, N. Stöveken, T. Hoffmann, B.R. Belitsky, A.L. Sonenshein, and E. Bremer. (2012). Proline utilization by Bacillus subtilis: uptake and catabolism. J. Bacteriol. 194: 745-758. 22139509
Naftalin, R.J. (2008). Osmotic water transport with glucose in GLUT2 and SGLT. Biophys. J. 94: 3912-3923. 18234816
Nagata, K. and Y. Hata. (2006). Substrate specificity of a chimera made from Xenopus SGLT1-like protein and rabbit SGLT1. Biochim. Biophys. Acta. 1758: 747-754. 16792998
Nicola, J.P., C. Basquin, C. Portulano, A. Reyna-Neyra, M. Paroder, and N. Carrasco. (2009). The Na+/I- symporter mediates active iodide uptake in the intestine. Am. J. Physiol. Cell Physiol. 296: C654-662. 19052257
Nishijyo, T., D. Haas, and Y. Itoh. (2001). The CbrA-CbrB two-component regulatory system controls the utilization of multiple carbon and nitrogen sources in Pseudomonas aeruginosa. Mol. Microbiol. 40: 917-931. 11401699
Niu, Y., R. Liu, C. Guan, Y. Zhang, Z. Chen, S. Hoerer, H. Nar, and L. Chen. (2022). Structural basis of inhibition of the human SGLT2-MAP17 glucose transporter. Nature 601: 280-284. 34880493
Okuda T., Osawa C., Yamada H., Hayashi K., Nishikawa S., Ushio T., Kubo Y., Satou M., Ogawa H. and Haga T. (2012). Transmembrane topology and oligomeric structure of the high-affinity choline transporter. J Biol Chem. 287(51):42826-34. 23132865
Okuda, T. and T. Haga. (2000). Functional characterization of the human high-affinity choline transporter. FEBS Lett. 484: 92-97. 11068039
Okuda, T., T. Haga, Y. Kanai, H. Endou, T. Ishihara, and I. Katsura. (2000). Identification and characterization of the high-affinity choline transporter. Nature Neurosci. 3: 120-125. 10649566
Pao, G.M. and M.H. Saier, Jr. (1995). Response regulators of bacterial signal transduction systems: selective domain shuffling during evolution. J. Molec. Evol. 40: 136-154. 7699720
Paroder-Belenitsky, M., M.J. Maestas, O. Dohán, J.P. Nicola, A. Reyna-Neyra, A. Follenzi, E. Dadachova, S. Eskandari, L.M. Amzel, and N. Carrasco. (2011). Mechanism of anion selectivity and stoichiometry of the Na+/I- symporter (NIS). Proc. Natl. Acad. Sci. USA 108: 17933-17938. 22011571
Perez, C. and C. Ziegler. (2013). Mechanistic aspects of sodium-binding sites in LeuT-like fold symporters. Biol Chem 394: 641-648. 23362203
Plata C., C.R. Sussman, A. Sindic, J.O. Liang, D.B. Mount, Z.M. Josephs, M.H. Chang, M.F. Romero. (2007). Zebrafish Slc5a12 encodes an electroneutral sodium monocarboxylate transporter (SMCTn). A comparison with the electrogenic SMCT (SMCTe/Slc5a8). J. Biol. Chem. 282: 11996-12009. 17255103
Portulano, C., M. Paroder-Belenitsky, and N. Carrasco. (2014). The Na+/I(-) Symporter (NIS): Mechanism and Medical Impact. Endocr Rev 35: 106-149. 24311738
Prasad, P.D., H. Wang, R. Kekuda, T. Fujita, Y.-J. Fei, L.D. Devoe, F.H. Leibach, and V. Ganapathy. (1998). Cloning and functional expression of a cDNA encoding a mammalian sodium-dependent vitamin transporter mediating the uptake of pantothenate, biotin, and lipoate. J. Biol. Chem. 273: 7501-7506. 9516450
Quick, M., D.D.F. Loo, and E.M. Wright. (2001). Neutralization of a conserved amino acid residue in the human Na+/glucose transporter (hSGLT1) generates a glucose-gated H+ channel. J. Biol. Chem. 276: 1728-1734. 11024018
Raba, M., S. Dunkel, D. Hilger, K. Lipiszko, Y. Polyhach, G. Jeschke, S. Bracher, J.P. Klare, M. Quick, H. Jung, and H.J. Steinhoff. (2014). Extracellular Loop 4 of the Proline Transporter PutP Controls the Periplasmic Entrance to Ligand Binding Sites. Structure 22: 769-780. 24768113
Reizer, J., A. Reizer, and M.H. Saier, Jr. (1991). The Na+/pantothenate symporter (PanF) of Escherichia coli is homologous to the Na+/proline symporter (PutP) of E. coli and the Na+/glucose symporters of mammals. Res. Microbiol. 141: 1069-1072. 1965458
Reizer, J., A. Reizer, and M.H. Saier, Jr. (1994). A functional superfamily of sodium/solute symporters. Biochim. Biophys. Acta 1197: 133-166. 8031825
Reyna-Neyra, A., L. Jung, M. Chakrabarti, M. Suarez, L.M. Amzel, and N. Carrasco. (2021). The iodide transport defect-causing Y348D mutation in the Na/I symporter (NIS) renders the protein intrinsically inactive and impairs its targeting to the plasma membrane. Thyroid. [Epub: Ahead of Print] 33779310
Rivera-Ordaz, A., S. Bracher, S. Sarrach, Z. Li, L. Shi, M. Quick, D. Hilger, R. Haas, and H. Jung. (2013). The Sodium/Proline Transporter PutP of Helicobacter pylori. PLoS One 8: e83576. 24358297
Rodionov, D.A., C. Yang, X. Li, I.A. Rodionova, Y. Wang, A.Y. Obraztsova, O.P. Zagnitko, R. Overbeek, M.F. Romine, S. Reed, J.K. Fredrickson, K.H. Nealson, and A.L. Osterman. (2010). Genomic encyclopedia of sugar utilization pathways in the Shewanella genus. BMC Genomics 11: 494. 20836887
Sanguinetti, M., A. Iriarte, S. Amillis, M. Marín, H. Musto, and A. Ramón. (2019). A pair of non-optimal codons are necessary for the correct biosynthesis of the urea transporter, UreA. R Soc Open Sci 6: 190773. 31827830
Sanguinetti, M., S. Amillis, S. Pantano, C. Scazzocchio, and A. Ramón. (2014). Modelling and mutational analysis of Aspergillus nidulans UreA, a member of the subfamily of urea/H⁺ transporters in fungi and plants. Open Biol 4: 140070. 24966243
Sarker, R.I., W. Ogawa, T. Shimamoto, T. Shimamoto, and T. Tsuchiya. (1997). Primary structure and properties of the Na+/glucose symporter (SglS) of Vibrio parahaemolyticus. J. Bacteriol. 179: 1805-1808. 9045844
Sasseville, L.J., J.P. Longpré, B. Wallendorff, and J.Y. Lapointe. (2014). The transport mechanism of the human sodium/myo-inositol transporter 2 (SMIT2/SGLT6), a member of the LeuT structural family. Am. J. Physiol. Cell Physiol. 307: C431-441. 24944204
Sasseville, L.J., M. Morin, M.J. Coady, R. Blunck, and J.Y. Lapointe. (2016). The Human Sodium-Glucose Cotransporter (hSGLT1) Is a Disulfide-Bridged Homodimer with a Re-Entrant C-Terminal Loop. PLoS One 11: e0154589. 27137918
Sever, M. and F. Merzel. (2023). Collective Domain Motion Facilitates Water Transport in SGLT1. Int J Mol Sci 24:. 37445706
Sever, M. and F. Merzel. (2023). Influence of SGLT1 Sugar Uptake Inhibitors on Water Transport. Molecules 28:. 37513169
Severi, E., A.H. Hosie, J.A. Hawkhead, and G.H. Thomas. (2010). Characterization of a novel sialic acid transporter of the sodium solute symporter (SSS) family and in vivo comparison with known bacterial sialic acid transporters. FEMS Microbiol. Lett. 304: 47-54. 20100283
Singh, A.K. and R. Singh. (2020). Cardiovascular outcomes with SGLT-2 inhibitors and GLP-1 receptor agonist in Asians with type 2 diabetes: A systematic review and meta-analysis of cardiovascular outcome trials. Diabetes Metab Syndr 14: 715-722. 32470852
Singh, T.D., J.E. Lee, K.H. Son, B.R. Lee, S.K. Kim, D. Gulwani, V. Sarangthem, and Y.H. Jeon. (2023). An Inverse Agonist of Estrogen-Related Receptor Gamma, GSK5182, Enhances Na/I Symporter Function in Radioiodine-Refractory Papillary Thyroid Cancer Cells. Cells 12:. 36766812
Spiegelhalter, F. and E. Bremer. (1998). Osmoregulation of the opuE proline transport gene from Bacillus subtilis: contributions of the sigma A- and sigma B-dependent stress-responsive promoters. Mol. Microbiol. 29: 285-296. 9701821
Stoupa, A., G. Al Hage Chehade, D. Kariyawasam, C. Tohier, C. Bole-Feysot, P. Nitschke, H. Thibault, M.L. Jullie, M. Polak, and A. Carré. (2020). First case of fetal goitrous hypothyroidism due to SLC5A5/NIS mutations. Eur J Endocrinol 183: K1-K5. 32805706
Su, X., R. Li, K.F. Kong, and J.S. Tsang. (2016). Transport of haloacids across biological membranes. Biochim. Biophys. Acta. 1858: 3061-3070. 27668346
Tatsumi KI., Fujiwara H., Tanaka S. and Amino N. (201). Characterization of Thr-354 in the human sodium/iodide symporter (NIS) by site-directed mutagenesis. Endocr J. 57(11):997-9. 20834191
Turk, E. and E.M. Wright. (1997). Membrane topology motifs in the SGLT cotransporter family. J. Membr. Biol. 159: 1-20. 9309206
Turk, E., O. Kim, J. le Coutre, J.P. Whitelegge, S. Eskandari, J.T. Lam, M. Kreman, G. Zampighi, K.F. Faull, and E.M. Wright. (2000). Molecular characterization of Vibrio parahaemolyticus vSGLT: a model for sodium-coupled sugar cotransporters. J. Biol. Chem. 275: 25711-25716. 10835424
Turk, E., O.K. Gasymov, S. Lanza, J. Horwitz, and E.M. Wright. (2006). A reinvestigation of the secondary structure of functionally active vSGLT, the vibrio sodium/galactose cotransporter. Biochemistry 45: 1470-1479. 16445289
Uemura, T., K. Kashiwagi, and K. Igarashi. (2007). Polyamine uptake by DUR3 and SAM3 in Saccharomyces cerevisiae. J. Biol. Chem. 282: 7733-7741. 17218313
Vadlapudi AD., Vadlapatla RK., Pal D. and Mitra AK. (2012). Functional and molecular aspects of biotin uptake via SMVT in human corneal epithelial (HCEC) and retinal pigment epithelial (D407) cells. AAPS J. 14(4):832-42. 22927035
Vadlapudi, A.D., R.K. Vadlapatla, and A.K. Mitra. (2012). Sodium dependent multivitamin transporter (SMVT): a potential target for drug delivery. Curr Drug Targets 13: 994-1003. 22420308
Vallari, D.S. and C.O. Rock. (1985). Isolation and characterization of Escherichia coli pantothenate permease (panF) mutants. J. Bacteriol. 164: 136-142. 2995306
Veenstra, M., S. Lanza, B.A. Hirayama, E. Turk, and E.M. Wright. (2004). Local conformational changes in the Vibrio Na+/galactose cotransporter. Biochemistry 43: 3620-3627. 15035632
Velic, A., J.R. Hirsch, J. Bartel, R. Thomas, R. Schröter, H. Stegemann, B. Edemir, C. August, E. Schlatter, and G. Gabriëls. (2004). Renal transplantation modulates expression and function of receptors and transporters of rat proximal tubules. J Am Soc Nephrol 15: 967-977. 15034099
von Blohn, C., B. Kempf, R.M. Kappes, and E. Bremer. (1997). Osmostress response in Bacillus subtilis: characterization of a proline uptake system (OpuE) regulated by high osmolarity and the alternative transcription factor sigma B. Mol. Microbiol. 25: 175-187. 11902719
Wang X., Xu X., Ma M., Zhou W., Wang Y. and Yang L. (2012). pH-dependent channel gating in connexin26 hemichannels involves conformational changes in N-terminus. Biochim Biophys Acta. 1818(5):1148-1157. 22285739
Wang, H., W. Huang, Y.-J. Fei, H. Xia, T.L. Yang-Feng, F.H. Leibach, L.D. Devoe, V. Ganapathy, and P.D. Prasad. (1999). Human placental Na+-dependent multivitamin transporter. J. Biol. Chem. 274: 14875-14883. 10329687
Wang, X.X., J. Levi, Y. Luo, K. Myakala, M. Herman-Edelstein, L. Qiu, D. Wang, Y. Peng, A. Grenz, S. Lucia, E. Dobrinskikh, V.D. D''Agati, H. Koepsell, J.B. Kopp, A. Rosenberg, and M. Levi. (2017). SGLT2 Expression is increased in Human Diabetic Nephropathy: SGLT2 Inhibition Decreases Renal Lipid Accumulation, Inflammation and the Development of Nephropathy in Diabetic Mice. J. Biol. Chem. [Epub: Ahead of Print] 28196866
Wargacki, A.J., E. Leonard, M.N. Win, D.D. Regitsky, C.N. Santos, P.B. Kim, S.R. Cooper, R.M. Raisner, A. Herman, A.B. Sivitz, A. Lakshmanaswamy, Y. Kashiyama, D. Baker, and Y. Yoshikuni. (2012). An engineered microbial platform for direct biofuel production from brown macroalgae. Science 335: 308-313. 22267807
Watanabe, A., S. Choe, V. Chaptal, J.M. Rosenberg, E.M. Wright, M. Grabe, and J. Abramson. (2010). The mechanism of sodium and substrate release from the binding pocket of vSGLT. Nature 468: 988-991. 21131949
Watanabe, Y., R.S. Ebrhim, M.A. Abdullah, and R.E. Weiss. (2018). A Novel Missense Mutation in the SLC5A5 Gene in a Sudanese Family with Congenital Hypothyroidism. Thyroid 28: 1068-1070. 29759035
Weston, E., F. Pangilinan, S. Eaton, M. Orford, K.Y. Leung, A.J. Copp, J.L. Mills, A.M. Molloy, L.C. Brody, and N. Greene. (2022). Investigating Genetic Determinants of Plasma Inositol Status in Adult Humans. J Nutr 152: 2333-2342. 36774100
Wilson MC., Meredith D., Bunnun C., Sessions RB. and Halestrap AP. (2009). Studies on the DIDS-binding site of monocarboxylate transporter 1 suggest a homology model of the open conformation and a plausible translocation cycle. J Biol Chem. 284(30):20011-21. 19473976
Xie, Z., E. Turk, and E.M. Wright. (2000). Characterization of the Vibrio parahaemolyticus Na+/glucose cotransporter: a bacterial member of the sodium/glucose transporter (SGLT) family. J. Biol Chem. 275: 25959-25964. 10852908
Xiong, Y., D. Delic, S. Zeng, X. Chen, C. Chu, A.A. Hasan, B.K. Krämer, T. Klein, L. Yin, and B. Hocher. (2022). Regulation of SARS CoV-2 host factors in the kidney and heart in rats with 5/6 nephrectomy-effects of salt, ARB, DPP4 inhibitor and SGLT2 blocker. BMC Nephrol 23: 117. 35331159
Yoshida, K., H. Yamaguchi, M. Kinehara, Y.H. Ohki, Y. Nakaura, and Y. Fujita. (2003). Identification of additional TnrA-regulated genes of Bacillus subtilis associated with a TnrA box. Mol. Microbiol. 49: 157-165. 12823818
Zhang, C.X., J.X. Zhang, L. Yang, C.R. Zhang, F. Cheng, R.J. Zhang, Y. Fang, Z. Wang, F.Y. Wu, P.Z. Li, J. Liang, R. Li, and H.D. Song. (2021). Novel Compound Heterozygous Pathogenic Mutations of in a Chinese Patient With Congenital Hypothyroidism. Front Endocrinol (Lausanne) 12: 620117. 33815280
Zhuge, X., Y. Sun, M. Jiang, J. Wang, F. Tang, F. Xue, J. Ren, W. Zhu, and J. Dai. (2019). Acetate metabolic requirement of avian pathogenic Escherichia coli promotes its intracellular proliferation within macrophage. Vet Res 50: 31. 31046828