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
- Functionssymporter activityProcessesapoptotic process / ion transport / sodium ion transport / transmembrane transportComponentsapical 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
- SSF (PF00474)
- 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
Resource Link UniProtKB ID Q8N695 UniProtKB Entry Name SC5A8_HUMAN HGNC ID HGNC:19119 - General References
- 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]
- 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]
- 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]
- 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]
- 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]
- 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]
- 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]
- 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]
- 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]
- 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]
- 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]
- 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]
- 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]
- 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 ID Name Drug group Pharmacological action? Actions Details DB00627 Niacin approved, investigational, nutraceutical unknown Details DB01762 Acetoacetic acid experimental unknown Details DB08872 Gabapentin enacarbil approved, investigational no substrate Details DB08949 Inositol nicotinate approved, withdrawn unknown substrate Details DB00121 Biotin approved, investigational, nutraceutical unknown substrate Details