Sodium-coupled monocarboxylate transporter 1

Details

Name
Sodium-coupled monocarboxylate transporter 1
Synonyms
  • AIT
  • Apical iodide transporter
  • Electrogenic sodium monocarboxylate cotransporter
  • SMCT
  • SMCT1
  • Sodium iodide-related cotransporter
  • Solute carrier family 5 member 8
Gene Name
SLC5A8
Organism
Humans
Amino acid sequence
>lcl|BSEQ0013272|Sodium-coupled monocarboxylate transporter 1
MDTPRGIGTFVVWDYVVFAGMLVISAAIGIYYAFAGGGQQTSKDFLMGGRRMTAVPVALS
LTASFMSAVTVLGTPSEVYRFGAIFSIFAFTYFFVVVISAEVFLPVFYKLGITSTYEYLE
LRFNKCVRLCGTVLFIVQTILYTGIVIYAPALALNQVTGFDLWGAVVATGVVCTFYCTLG
GLKAVIWTDVFQVGIMVAGFASVIIQAVVMQGGISTILNDAYDGGRLNFWNFNPNPLQRH
TFWTIIIGGTFTWTSIYGVNQSQVQRYISCKSRFQAKLSLYINLVGLWAILTCSVFCGLA
LYSRYHDCDPWTAKKVSAPDQLMPYLVLDILQDYPGLPGLFVACAYSGTLSTVSSSINAL
AAVTVEDLIKPYFRSLSERSLSWISQGMSVVYGALCIGMAALASLMGALLQAALSVFGMV
GGPLMGLFALGILVPFANSIGALVGLMAGFAISLWVGIGAQIYPPLPERTLPLHLDIQGC
NSTYNETNLMTTTEMPFTTSVFQIYNVQRTPLMDNWYSLSYLYFSTVGTLVTLLVGILVS
LSTGGRKQNLDPRYILTKEDFLSNFDIFKKKKHVLSYKSHPVEDGGTDNPAFNHIELNSD
QSGKSNGTRL
Number of residues
610
Molecular Weight
66577.005
Theoretical pI
Not Available
GO Classification
Functions
symporter activity
Processes
apoptotic process / ion transport / sodium ion transport / transmembrane transport
Components
apical plasma membrane / extracellular exosome / integral component of membrane / plasma membrane
General Function
Symporter activity
Specific Function
Acts as an electrogenic sodium (Na(+)) and chloride (Cl-)-dependent sodium-coupled solute transporter, including transport of monocarboxylates (short-chain fatty acids including L-lactate, D-lactate, pyruvate, acetate, propionate, valerate and butyrate), lactate, mocarboxylate drugs (nicotinate, benzoate, salicylate and 5-aminosalicylate) and ketone bodies (beta-D-hydroxybutyrate, acetoacetate and alpha-ketoisocaproate), with a Na(+):substrate stoichiometry of between 4:1 and 2:1. Catalyzes passive carrier mediated diffusion of iodide. Mediates iodide transport from the thyrocyte into the colloid lumen through the apical membrane. May be responsible for the absorption of D-lactate and monocarboxylate drugs from the intestinal tract. Acts as a tumor suppressor, suppressing colony formation in colon cancer, prostate cancer and glioma cell lines. May play a critical role in the entry of L-lactate and ketone bodies into neurons by a process driven by an electrochemical Na(+) gradient and hence contribute to the maintenance of the energy status and function of neurons.
Pfam Domain Function
Transmembrane Regions
10-30 52-72 84-104 133-153 162-182 190-210 240-260 280-300 337-359 390-410 416-436 440-460 519-539
Cellular Location
Apical cell membrane
Gene sequence
>lcl|BSEQ0013273|Sodium-coupled monocarboxylate transporter 1 (SLC5A8)
ATGGACACGCCACGGGGCATCGGCACCTTCGTGGTGTGGGACTACGTGGTGTTCGCGGGC
ATGCTGGTCATCTCGGCCGCCATCGGCATCTACTACGCCTTCGCTGGGGGCGGCCAGCAG
ACCTCCAAGGACTTCCTGATGGGCGGCCGCAGAATGACCGCAGTGCCCGTGGCGCTGTCC
CTCACCGCTAGCTTCATGTCAGCCGTCACTGTCCTGGGCACCCCCTCCGAGGTCTACCGT
TTTGGGGCCATTTTTAGCATCTTTGCCTTCACCTACTTCTTTGTGGTGGTCATCAGCGCG
GAGGTCTTCCTCCCGGTGTTCTACAAACTGGGAATTACCAGCACCTACGAGTATTTAGAA
CTTCGATTTAACAAATGTGTTCGTCTCTGTGGAACAGTCCTCTTCATTGTTCAAACAATT
CTGTATACTGGAATTGTTATTTATGCCCCTGCCCTGGCTTTGAATCAAGTCACAGGATTT
GATCTGTGGGGCGCGGTAGTGGCAACGGGGGTGGTCTGCACATTCTACTGCACACTGGGT
GGTCTTAAAGCAGTTATCTGGACAGATGTTTTTCAAGTTGGGATCATGGTGGCTGGATTT
GCATCCGTGATTATACAGGCTGTGGTGATGCAAGGTGGAATCAGCACTATTTTAAATGAT
GCCTATGATGGTGGAAGATTAAATTTCTGGAATTTTAATCCTAACCCTTTGCAAAGACAC
ACCTTCTGGACAATTATTATAGGAGGGACCTTCACATGGACCAGCATCTACGGTGTCAAC
CAATCCCAGGTGCAGAGATATATTTCTTGTAAAAGCAGATTCCAGGCAAAACTGTCTCTC
TACATCAATCTTGTGGGACTCTGGGCAATCCTCACATGCTCAGTGTTTTGTGGGCTCGCC
CTATATTCCAGGTACCATGACTGTGATCCTTGGACAGCCAAGAAAGTGTCTGCACCAGAC
CAGCTCATGCCTTATTTGGTACTGGACATTCTGCAAGATTATCCAGGACTTCCTGGACTT
TTTGTGGCCTGTGCTTACAGTGGGACATTAAGCACAGTGTCCTCCAGTATTAATGCCTTA
GCAGCAGTAACTGTGGAAGATCTAATCAAACCTTACTTCAGATCGCTCTCAGAAAGGTCT
CTGTCTTGGATTTCCCAAGGAATGAGTGTGGTGTATGGAGCCCTGTGTATTGGAATGGCT
GCGCTGGCGTCACTTATGGGAGCTTTGTTGCAGGCAGCACTCAGCGTATTTGGTATGGTT
GGTGGACCACTTATGGGCCTGTTCGCTTTGGGCATTTTGGTTCCCTTTGCCAACTCAATT
GGAGCACTTGTTGGTCTGATGGCTGGATTTGCCATTTCTCTATGGGTTGGAATTGGAGCT
CAAATATATCCTCCACTTCCTGAGAGAACATTGCCATTGCACCTTGATATCCAAGGCTGT
AACAGCACCTACAATGAGACAAATTTGATGACAACCACAGAAATGCCATTTACTACTAGT
GTTTTTCAAATATACAATGTTCAAAGGACTCCACTGATGGATAACTGGTATTCTTTATCA
TATCTGTACTTCAGCACTGTTGGAACTTTGGTAACATTATTAGTGGGGATACTTGTCAGT
TTATCAACAGGAGGAAGAAAACAGAACTTAGACCCCAGATACATACTAACCAAAGAGGAC
TTTTTATCCAATTTTGATATTTTTAAGAAAAAGAAGCATGTTTTGAGCTATAAATCACAT
CCAGTGGAAGATGGTGGAACTGATAATCCTGCTTTCAACCACATTGAATTGAACTCAGAT
CAGAGTGGCAAGAGCAATGGGACTCGTTTGTGA
Chromosome Location
12
Locus
Not Available
External Identifiers
ResourceLink
UniProtKB IDQ8N695
UniProtKB Entry NameSC5A8_HUMAN
HGNC IDHGNC:19119
General References
  1. Rodriguez AM, Perron B, Lacroix L, Caillou B, Leblanc G, Schlumberger M, Bidart JM, Pourcher T: Identification and characterization of a putative human iodide transporter located at the apical membrane of thyrocytes. J Clin Endocrinol Metab. 2002 Jul;87(7):3500-3. [Article]
  2. 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: SLC5A8, a sodium transporter, is a tumor suppressor gene silenced by methylation in human colon aberrant crypt foci and cancers. Proc Natl Acad Sci U S A. 2003 Jul 8;100(14):8412-7. Epub 2003 Jun 26. [Article]
  3. Miyauchi S, Gopal E, Fei YJ, Ganapathy V: 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. 2004 Apr 2;279(14):13293-6. Epub 2004 Feb 13. [Article]
  4. Coady MJ, Chang MH, Charron FM, Plata C, Wallendorff B, Sah JF, Markowitz SD, Romero MF, Lapointe JY: The human tumour suppressor gene SLC5A8 expresses a Na+-monocarboxylate cotransporter. J Physiol. 2004 Jun 15;557(Pt 3):719-31. Epub 2004 Apr 16. [Article]
  5. Scherer SE, Muzny DM, Buhay CJ, Chen R, Cree A, Ding Y, Dugan-Rocha S, Gill R, Gunaratne P, Harris RA, Hawes AC, Hernandez J, Hodgson AV, Hume J, Jackson A, Khan ZM, Kovar-Smith C, Lewis LR, Lozado RJ, Metzker ML, Milosavljevic A, Miner GR, Montgomery KT, Morgan MB, Nazareth LV, Scott G, Sodergren E, Song XZ, Steffen D, Lovering RC, Wheeler DA, Worley KC, Yuan Y, Zhang Z, Adams CQ, Ansari-Lari MA, Ayele M, Brown MJ, Chen G, Chen Z, Clerc-Blankenburg KP, Davis C, Delgado O, Dinh HH, Draper H, Gonzalez-Garay ML, Havlak P, Jackson LR, Jacob LS, Kelly SH, Li L, Li Z, Liu J, Liu W, Lu J, Maheshwari M, Nguyen BV, Okwuonu GO, Pasternak S, Perez LM, Plopper FJ, Santibanez J, Shen H, Tabor PE, Verduzco D, Waldron L, Wang Q, Williams GA, Zhang J, Zhou J, Allen CC, Amin AG, Anyalebechi V, Bailey M, Barbaria JA, Bimage KE, Bryant NP, Burch PE, Burkett CE, Burrell KL, Calderon E, Cardenas V, Carter K, Casias K, Cavazos I, Cavazos SR, Ceasar H, Chacko J, Chan SN, Chavez D, Christopoulos C, Chu J, Cockrell R, Cox CD, Dang M, Dathorne SR, David R, Davis CM, Davy-Carroll L, Deshazo DR, Donlin JE, D'Souza L, Eaves KA, Egan A, Emery-Cohen AJ, Escotto M, Flagg N, Forbes LD, Gabisi AM, Garza M, Hamilton C, Henderson N, Hernandez O, Hines S, Hogues ME, Huang M, Idlebird DG, Johnson R, Jolivet A, Jones S, Kagan R, King LM, Leal B, Lebow H, Lee S, LeVan JM, Lewis LC, London P, Lorensuhewa LM, Loulseged H, Lovett DA, Lucier A, Lucier RL, Ma J, Madu RC, Mapua P, Martindale AD, Martinez E, Massey E, Mawhiney S, Meador MG, Mendez S, Mercado C, Mercado IC, Merritt CE, Miner ZL, Minja E, Mitchell T, Mohabbat F, Mohabbat K, Montgomery B, Moore N, Morris S, Munidasa M, Ngo RN, Nguyen NB, Nickerson E, Nwaokelemeh OO, Nwokenkwo S, Obregon M, Oguh M, Oragunye N, Oviedo RJ, Parish BJ, Parker DN, Parrish J, Parks KL, Paul HA, Payton BA, Perez A, Perrin W, Pickens A, Primus EL, Pu LL, Puazo M, Quiles MM, Quiroz JB, Rabata D, Reeves K, Ruiz SJ, Shao H, Sisson I, Sonaike T, Sorelle RP, Sutton AE, Svatek AF, Svetz LA, Tamerisa KS, Taylor TR, Teague B, Thomas N, Thorn RD, Trejos ZY, Trevino BK, Ukegbu ON, Urban JB, Vasquez LI, Vera VA, Villasana DM, Wang L, Ward-Moore S, Warren JT, Wei X, White F, Williamson AL, Wleczyk R, Wooden HS, Wooden SH, Yen J, Yoon L, Yoon V, Zorrilla SE, Nelson D, Kucherlapati R, Weinstock G, Gibbs RA: The finished DNA sequence of human chromosome 12. Nature. 2006 Mar 16;440(7082):346-51. [Article]
  6. Gerhard DS, Wagner L, Feingold EA, Shenmen CM, Grouse LH, Schuler G, Klein SL, Old S, Rasooly R, Good P, Guyer M, Peck AM, Derge JG, Lipman D, Collins FS, Jang W, Sherry S, Feolo M, Misquitta L, Lee E, Rotmistrovsky K, Greenhut SF, Schaefer CF, Buetow K, Bonner TI, Haussler D, Kent J, Kiekhaus M, Furey T, Brent M, Prange C, Schreiber K, Shapiro N, Bhat NK, Hopkins RF, Hsie F, Driscoll T, Soares MB, Casavant TL, Scheetz TE, Brown-stein MJ, Usdin TB, Toshiyuki S, Carninci P, Piao Y, Dudekula DB, Ko MS, Kawakami K, Suzuki Y, Sugano S, Gruber CE, Smith MR, Simmons B, Moore T, Waterman R, Johnson SL, Ruan Y, Wei CL, Mathavan S, Gunaratne PH, Wu J, Garcia AM, Hulyk SW, Fuh E, Yuan Y, Sneed A, Kowis C, Hodgson A, Muzny DM, McPherson J, Gibbs RA, Fahey J, Helton E, Ketteman M, Madan A, Rodrigues S, Sanchez A, Whiting M, Madari A, Young AC, Wetherby KD, Granite SJ, Kwong PN, Brinkley CP, Pearson RL, Bouffard GG, Blakesly RW, Green ED, Dickson MC, Rodriguez AC, Grimwood J, Schmutz J, Myers RM, Butterfield YS, Griffith M, Griffith OL, Krzywinski MI, Liao N, Morin R, Palmquist D, Petrescu AS, Skalska U, Smailus DE, Stott JM, Schnerch A, Schein JE, Jones SJ, Holt RA, Baross A, Marra MA, Clifton S, Makowski KA, Bosak S, Malek J: The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC). Genome Res. 2004 Oct;14(10B):2121-7. [Article]
  7. Lacroix L, Pourcher T, Magnon C, Bellon N, Talbot M, Intaraphairot T, Caillou B, Schlumberger M, Bidart JM: Expression of the apical iodide transporter in human thyroid tissues: a comparison study with other iodide transporters. J Clin Endocrinol Metab. 2004 Mar;89(3):1423-8. [Article]
  8. 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: Aberrant methylation and histone deacetylation associated with silencing of SLC5A8 in gastric cancer. Tumour Biol. 2004 May-Jun;25(3):134-40. [Article]
  9. Hong C, Maunakea A, Jun P, Bollen AW, Hodgson JG, Goldenberg DD, Weiss WA, Costello JF: Shared epigenetic mechanisms in human and mouse gliomas inactivate expression of the growth suppressor SLC5A8. Cancer Res. 2005 May 1;65(9):3617-23. [Article]
  10. Thangaraju M, Gopal E, Martin PM, Ananth S, Smith SB, Prasad PD, Sterneck E, Ganapathy V: SLC5A8 triggers tumor cell apoptosis through pyruvate-dependent inhibition of histone deacetylases. Cancer Res. 2006 Dec 15;66(24):11560-4. [Article]
  11. Martin PM, Gopal E, Ananth S, Zhuang L, Itagaki S, Prasad BM, Smith SB, Prasad PD, Ganapathy V: Identity of SMCT1 (SLC5A8) as a neuron-specific Na+-coupled transporter for active uptake of L-lactate and ketone bodies in the brain. J Neurochem. 2006 Jul;98(1):279-88. [Article]
  12. Itagaki S, Gopal E, Zhuang L, Fei YJ, Miyauchi S, Prasad PD, Ganapathy V: Interaction of ibuprofen and other structurally related NSAIDs with the sodium-coupled monocarboxylate transporter SMCT1 (SLC5A8). Pharm Res. 2006 Jun;23(6):1209-16. Epub 2006 Jun 1. [Article]
  13. Park JY, Zheng W, Kim D, Cheng JQ, Kumar N, Ahmad N, Pow-Sang J: Candidate tumor suppressor gene SLC5A8 is frequently down-regulated by promoter hypermethylation in prostate tumor. Cancer Detect Prev. 2007;31(5):359-65. Epub 2007 Nov 26. [Article]
  14. Gopal E, Miyauchi S, Martin PM, Ananth S, Roon P, Smith SB, Ganapathy V: Transport of nicotinate and structurally related compounds by human SMCT1 (SLC5A8) and its relevance to drug transport in the mammalian intestinal tract. Pharm Res. 2007 Mar;24(3):575-84. [Article]

Drug Relations

Drug Relations
DrugBank IDNameDrug groupPharmacological action?ActionsDetails
DB00627Niacinapproved, investigational, nutraceuticalunknownDetails
DB01762Acetoacetic acidexperimentalunknownDetails
DB08872Gabapentin enacarbilapproved, investigationalnosubstrateDetails
DB08949Inositol nicotinateapproved, withdrawnunknownsubstrateDetails
DB00121Biotinapproved, investigational, nutraceuticalunknownsubstrateDetails