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Identification
HMDB Protein ID HMDBP08227
Secondary Accession Numbers
  • 13939
Name Sodium-coupled monocarboxylate transporter 1
Synonyms
  1. Apical iodide transporter
  2. Electrogenic sodium monocarboxylate cotransporter
  3. Sodium iodide-related cotransporter
  4. Solute carrier family 5 member 8
Gene Name SLC5A8
Protein Type Unknown
Biological Properties
General Function Involved in transporter 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
Pathways Not Available
Reactions Not Available
GO Classification
Component
membrane
cell part
Function
transporter activity
Process
establishment of localization
transport
transmembrane transport
Cellular Location
  1. Multi-pass membrane protein
  2. Apical cell membrane
Gene Properties
Chromosome Location Chromosome:1
Locus 12q23.1
SNPs SLC5A8
Gene Sequence
>1833 bp
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
Protein Properties
Number of Residues 610
Molecular Weight 66577.0
Theoretical pI 7.83
Pfam Domain Function
Signals
  • None
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
Protein Sequence
>Sodium-coupled monocarboxylate transporter 1
MDTPRGIGTFVVWDYVVFAGMLVISAAIGIYYAFAGGGQQTSKDFLMGGRRMTAVPVALS
LTASFMSAVTVLGTPSEVYRFGAIFSIFAFTYFFVVVISAEVFLPVFYKLGITSTYEYLE
LRFNKCVRLCGTVLFIVQTILYTGIVIYAPALALNQVTGFDLWGAVVATGVVCTFYCTLG
GLKAVIWTDVFQVGIMVAGFASVIIQAVVMQGGISTILNDAYDGGRLNFWNFNPNPLQRH
TFWTIIIGGTFTWTSIYGVNQSQVQRYISCKSRFQAKLSLYINLVGLWAILTCSVFCGLA
LYSRYHDCDPWTAKKVSAPDQLMPYLVLDILQDYPGLPGLFVACAYSGTLSTVSSSINAL
AAVTVEDLIKPYFRSLSERSLSWISQGMSVVYGALCIGMAALASLMGALLQAALSVFGMV
GGPLMGLFALGILVPFANSIGALVGLMAGFAISLWVGIGAQIYPPLPERTLPLHLDIQGC
NSTYNETNLMTTTEMPFTTSVFQIYNVQRTPLMDNWYSLSYLYFSTVGTLVTLLVGILVS
LSTGGRKQNLDPRYILTKEDFLSNFDIFKKKKHVLSYKSHPVEDGGTDNPAFNHIELNSD
QSGKSNGTRL
GenBank ID Protein 167466278
UniProtKB/Swiss-Prot ID Q8N695
UniProtKB/Swiss-Prot Entry Name SC5A8_HUMAN
PDB IDs Not Available
GenBank Gene ID NM_145913.3
GeneCard ID SLC5A8
GenAtlas ID SLC5A8
HGNC ID HGNC:19119
References
General References
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  3. 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. [PubMed:12107270 ]
  4. 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. [PubMed:12829793 ]
  5. 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. [PubMed:14966140 ]
  6. 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. [PubMed:15090606 ]
  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. [PubMed:15001644 ]
  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. [PubMed:15361710 ]
  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. [PubMed:15867356 ]
  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. [PubMed:17178845 ]
  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. [PubMed:16805814 ]
  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. [PubMed:16729224 ]
  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. [PubMed:18037591 ]
  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. [PubMed:17245649 ]