cd11519

Na(+)/monocarboxylate cotransporter SMCT1 and related proteins; solute-binding domain

CDD entry
Member databaseCDD
CDD typedomain
Short nameSLC5sbd_SMCT1
SetSLC5-6-like_sbd

Description

SMCT1 is a high-affinity transporter of various monocarboxylates including lactate and pyruvate, short-chain fatty acids, ketone bodies, nicotinate and its structural analogs, pyroglutamate, benzoate and its derivatives, and iodide. Human SMCT1 (hSMCT1, also called AIT) is encoded by the tumor suppressor gene SLC5A8. Its expression is under the control of the C/EBP transcription factor. Its tumor-suppressive role is related to uptake of butyrate, propionate, and pyruvate, these latter are inhibitors of histone deacetylases. SMCT1 is expressed in the colon, small intestine, kidney, thyroid gland, retina, and brain. SMCT1 may contribute to the intestinal/colonic and oral absorption of monocarboxylate drugs. SMCT1 also mediates iodide transport from thyrocyte into the colloid lumen in thyroid gland and through transporting l-lactate and ketone bodies helps maintain the energy status and the function of neurons. In the kidney its expression is limited to the S3 segment of the proximal convoluted tubule (in contrast to the low-affinity monocarboxylate transporter SMCT2, belonging to a different family, which is expressed along the entire length of the tubule). In the retina, SMCT1 and SMCT2 may play a differential role in monocarboxylate transport in a cell type-specific manner, SMCT1 is expressed predominantly in retinal neurons and in retinal pigmented epithelial (RPE) cells. This subgroup belongs to the solute carrier 5 (SLC5) transporter family.
[10, 16, 17, 3, 11, 15, 2, 13, 9, 5, 8, 4, 7, 1, 14, 12, 6]

References

1.Expression of slc5a8 in kidney and its role in Na(+)-coupled transport of lactate. Gopal E, Fei YJ, Sugawara M, Miyauchi S, Zhuang L, Martin P, Smith SB, Prasad PD, Ganapathy V. J Biol Chem 279, 44522-32, (2004). PMID: 15322102

2.SLC5A8 triggers tumor cell apoptosis through pyruvate-dependent inhibition of histone deacetylases. Thangaraju M, Gopal E, Martin PM, Ananth S, Smith SB, Prasad PD, Sterneck E, Ganapathy V. Cancer Res 66, 11560-4, (2006). PMID: 17178845

3.Shared epigenetic mechanisms in human and mouse gliomas inactivate expression of the growth suppressor SLC5A8. Hong C, Maunakea A, Jun P, Bollen AW, Hodgson JG, Goldenberg DD, Weiss WA, Costello JF. Cancer Res 65, 3617-23, (2005). PMID: 15867356

4.Functional identification of SLC5A8, a tumor suppressor down-regulated in colon cancer, as a Na(+)-coupled transporter for short-chain fatty acids. Miyauchi S, Gopal E, Fei YJ, Ganapathy V. J Biol Chem 279, 13293-6, (2004). PMID: 14966140

5.Identification and characterization of a putative human iodide transporter located at the apical membrane of thyrocytes. Rodriguez AM, Perron B, Lacroix L, Caillou B, Leblanc G, Schlumberger M, Bidart JM, Pourcher T. J. Clin. Endocrinol. Metab. 87, 3500-3, (2002). View articlePMID: 12107270

6.Expression of the sodium-coupled monocarboxylate transporters SMCT1 (SLC5A8) and SMCT2 (SLC5A12) in retina. Martin PM, Dun Y, Mysona B, Ananth S, Roon P, Smith SB, Ganapathy V. Invest. Ophthalmol. Vis. Sci. 48, 3356-63, (2007). View articlePMID: 17591909

7.The human tumour suppressor gene SLC5A8 expresses a Na+-monocarboxylate cotransporter. Coady MJ, Chang MH, Charron FM, Plata C, Wallendorff B, Sah JF, Markowitz SD, Romero MF, Lapointe JY. J Physiol 557, 719-31, (2004). PMID: 15090606

8.SLC5A8, a sodium transporter, is a tumor suppressor gene silenced by methylation in human colon aberrant crypt foci and cancers. Li H, Myeroff L, Smiraglia D, Romero MF, Pretlow TP, Kasturi L, Lutterbaugh J, Rerko RM, Casey G, Issa JP, Willis J, Willson JK, Plass C, Markowitz SD. Proc Natl Acad Sci U S A 100, 8412-7, (2003). PMID: 12829793

9.Candidate tumor suppressor gene SLC5A8 is frequently down-regulated by promoter hypermethylation in prostate tumor. Park JY, Zheng W, Kim D, Cheng JQ, Kumar N, Ahmad N, Pow-Sang J. Cancer Detect Prev 31, 359-65, (2007). PMID: 18037591

10.Surprising versatility of Na+-glucose cotransporters: SLC5. Wright EM, Loo DD, Hirayama BA, Turk E. Physiology (Bethesda) 19, 370-6, (2004). PMID: 15546855

11.Interaction of ibuprofen and other structurally related NSAIDs with the sodium-coupled monocarboxylate transporter SMCT1 (SLC5A8). Itagaki S, Gopal E, Zhuang L, Fei YJ, Miyauchi S, Prasad PD, Ganapathy V. Pharm Res 23, 1209-16, (2006). PMID: 16729224

12.Sodium-coupled electrogenic transport of pyroglutamate (5-oxoproline) via SLC5A8, a monocarboxylate transporter. Miyauchi S, Gopal E, Babu E, Srinivas SR, Kubo Y, Umapathy NS, Thakkar SV, Ganapathy V, Prasad PD. Biochim. Biophys. Acta 1798, 1164-71, (2010). View articlePMID: 20211600

13.Transport of nicotinate and structurally related compounds by human SMCT1 (SLC5A8) and its relevance to drug transport in the mammalian intestinal tract. Gopal E, Miyauchi S, Martin PM, Ananth S, Roon P, Smith SB, Ganapathy V. Pharm. Res. 24, 575-84, (2007). View articlePMID: 17245649

14.Identification and characterization of the human SLC5A8 gene promoter. Zhang Y, Bao YL, Wu Y, Yu CL, Sun Y, Li YX. Cancer Genet Cytogenet 196, 124-32, (2010). PMID: 20082847

15.Identity of SMCT1 (SLC5A8) as a neuron-specific Na+-coupled transporter for active uptake of L-lactate and ketone bodies in the brain. Martin PM, Gopal E, Ananth S, Zhuang L, Itagaki S, Prasad BM, Smith SB, Prasad PD, Ganapathy V. J. Neurochem. 98, 279-88, (2006). View articlePMID: 16805814

16.Biology of human sodium glucose transporters. Wright EM, Loo DD, Hirayama BA. Physiol. Rev. 91, 733-94, (2011). View articlePMID: 21527736

17.Aberrant methylation and histone deacetylation associated with silencing of SLC5A8 in gastric cancer. Ueno M, Toyota M, Akino K, Suzuki H, Kusano M, Satoh A, Mita H, Sasaki Y, Nojima M, Yanagihara K, Hinoda Y, Tokino T, Imai K. Tumour Biol 25, 134-40, (2004). PMID: 15361710

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