Atlas of Genetics and Cytogenetics in Oncology and Haematology


Home   Genes   Leukemias   Solid Tumours   Cancer-Prone   Deep Insight   Case Reports   Journals  Portal   Teaching   

X Y 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 NA

SLC16A1 (solute carrier family 16, member 1 (monocarboxylic acid transporter 1))

Identity

Other namesFLJ36745
HHF7
MCT
MCT1
MGC44475
HGNC (Hugo) SLC16A1
LocusID (NCBI) 6566
Location 1p13.2
Location_base_pair Starts at 113454470 and ends at 113498685 bp from pter ( according to hg19-Feb_2009)  [Mapping]

DNA/RNA

Note Human SLC16A1 was firstly cloned in 1994, by Garcia and colleagues. Structural gene organization as well as isolation and characterization of SLC16A1 promoter was achieved in 2002, by Cuff and Shirazi-Beechey.
Description 44507 bp lenght, containing 5 exons. Various SNPs have been described in SLC16A1 gene.
Transcription 6 transcripts have been described for this gene (4 with protein product, 2 with no protein product): SLC16A1-001 (5 exons; 3910 bps transcript length; 500 residues translation length); SLC16A1-002 (5 exons; 2101 bps transcript length; 456 residues translation length); SLC16A1-003 (4 exons; 865 bps transcript length; 215 residues translation length); SLC16A1-004 (2 exons; 452 bps transcript length; no translation product); SLC16A1-005 (4 exons; 1099 bps transcript length; 296 residues translation length); SLC16A1-006 (2 exons; 430 bps transcript length; no translation product).
Pseudogene 1 related pseudogene identified - AKR7 family pseudogene (AFARP1), non-coding RNA.

Protein

 
  Protein diagram drawn following UniProtKB/Swiss-Prot database prediction, using TMRPres2D software.
Description 500 amino acids; 53958 Da; 12 transmembrane domains, intracellular N- and C-terminal and a large intracellular loop between transmembrane domains 6 and 7.
Expression Ubiquitous.
Localisation Plasma membrane; also described in rat mitochondrial and peroxisomal membranes.
Function Catalyses the proton-linked transport of metabolically important monocarboxylates such as lactate, pyruvate, branched-chain oxo acids derived from leucine, valine and isoleucine, and ketone bodies (acetoacetate, beta-hydroxybutyrate and acetate).
Homology Belongs to the major facilitator superfamily (MFS). Monocarboxylate porter (TC 2.A.1.13) family. SLC16A1 gene is conserved in chimpanzee, dog, cow, mouse, rat, chicken, and zebrafish.

Implicated in

Entity Various cancers
Note MCT1/SLC16A1 has been described to be upregulated in a variety of tumours.
Disease High grade glial neoplasms (Mathupala et al., 2004; Fang et al., 2006), colorectal (Koukourakis et al., 2006; Pinheiro et al., 2008), lung (Koukourakis et al., 2007), cervical (Pinheiro et al., 2008), and breast carcinomas (Pinheiro et al., in Press).
  
Entity Breast cancer
Prognosis In breast cancer, MCT1/SLC16A1 was found to be associated with poor prognostic variables such as basal-like subtype and high grade tumours (Pinheiro et al., in Press).
Oncogenesis SLC16A1 is expressed in normal breast tissue, but is silenced in breast cancer due to gene methylation (Asada et al., 2003).
  
Entity Gastric cancer
Note The prognostic value of CD147 (a MCT1/SLC16A1 and MCT4/SLC16A3 chaperone required for plasma membrane expression and activity) was associated with MCT1/SLC16A1 co-expression in gastric cancer cells (Pinheiro et al., 2009).
Prognosis Co-expression of MCT1/SLC16A1 with CD147 was associated with advanced gastric carcinoma, Lauren's intestinal type, TNM staging and lymph-node metastasis, in gastric cancer.
  
Entity Colorectal carcinoma
Note MCT1/SLC16A1 has been described to be downregulated in colorectal carcinoma (Lamber et al., 2002).
  
Entity Erythrocyte lactate transporter defect
Note Merezhinskaya et al. (2000) identified two heterozygous transitions in the SLC16A1 gene, in patients with erythrocyte lactate transporter defect: 610A-G transition (resulting in a lys204-to-glu (K204E) substitution in a highly conserved residue) and 1414G-A transition (resulting in a gly472-to-arg (G472R) substitution halfway along the cytoplasmic C-terminal chain). These substitutions are not conserved, but were not identified in 90 healthy control individuals. Erythrocyte lactate clearance in patients with these mutations was 40 to 50% that of normal control values.
  
Entity Hyperinsulinemic hypoglycemia familial 7
Note Otonkoski et al. (2007) identified two heterozygotic alterations in the SLC16A1, in affected members of a Finnish family segregating autosomal dominant exercise-induced hyperinsulinemic hypoglycemia. First, a 163G-A transition in exon 1 located within a binding site for nuclear matrix protein-1 and predicted to disrupt the binding sites of 2 potential transcriptional repressors, and, secondly, a 25-bp insertion at nucleotide -24 introducing additional binding sites for the ubiquitous transcription factors SP1, USF and MZF1. The first variation leads to a 3-fold increase in transcription while the second variation leads to a 10-fold increase in transcription. These mutations were not found in 92 Finnish and German controls.
  

Other Solid tumors implicated (Data extracted from papers in the Atlas)

Solid Tumors AmeloblastomID5945

External links

Nomenclature
HGNC (Hugo)SLC16A1   10922
Cards
AtlasSLC16A1ID44046ch1p13
Entrez_Gene (NCBI)SLC16A1  6566  solute carrier family 16 (monocarboxylate transporter), member 1
GeneCards (Weizmann)SLC16A1
Ensembl (Hinxton)ENSG00000155380 [Gene_View]  chr1:113454470-113498685 [Contig_View]  SLC16A1 [Vega]
ICGC DataPortalENSG00000155380
cBioPortalSLC16A1
AceView (NCBI)SLC16A1
Genatlas (Paris)SLC16A1
WikiGenes6566
SOURCE (Princeton)NM_001166496 NM_003051
Genomic and cartography
GoldenPath (UCSC)SLC16A1  -  1p13.2   chr1:113454470-113498685 -  1p12   [Description]    (hg19-Feb_2009)
EnsemblSLC16A1 - 1p12 [CytoView]
Mapping of homologs : NCBISLC16A1 [Mapview]
OMIM245340   600682   610021   
Gene and transcription
Genbank (Entrez)AF239919 AI656300 AJ438942 AJ438943 AK000641
RefSeq transcript (Entrez)NM_001166496 NM_003051
RefSeq genomic (Entrez)AC_000133 NC_000001 NC_018912 NG_015880 NT_032977 NW_001838594 NW_004929290
Consensus coding sequences : CCDS (NCBI)SLC16A1
Cluster EST : UnigeneHs.75231 [ NCBI ]
CGAP (NCI)Hs.75231
Alternative Splicing : Fast-db (Paris)GSHG0002367
Alternative Splicing GalleryENSG00000155380
Gene ExpressionSLC16A1 [ NCBI-GEO ]     SLC16A1 [ SEEK ]   SLC16A1 [ MEM ]
Protein : pattern, domain, 3D structure
UniProt/SwissProtP53985 (Uniprot)
NextProtP53985  [Medical]
With graphics : InterProP53985
Splice isoforms : SwissVarP53985 (Swissvar)
Domaine pattern : Prosite (Expaxy)MFS (PS50850)   
Domains : Interpro (EBI)MFS [organisation]   MFS_dom [organisation]   MFS_dom_general_subst_transpt [organisation]   Monocarb_transpt [organisation]  
Related proteins : CluSTrP53985
Domain families : Pfam (Sanger)MFS_1 (PF07690)   
Domain families : Pfam (NCBI)pfam07690   
DMDM Disease mutations6566
Blocks (Seattle)P53985
Human Protein AtlasENSG00000155380 [gene] [tissue] [antibody] [cell] [cancer]
Peptide AtlasP53985
HPRD02816
IPIIPI00024650   IPI00910164   IPI00646589   IPI00645964   IPI00643709   
Protein Interaction databases
DIP (DOE-UCLA)P53985
IntAct (EBI)P53985
FunCoupENSG00000155380
BioGRIDSLC16A1
InParanoidP53985
Interologous Interaction database P53985
IntegromeDBSLC16A1
STRING (EMBL)SLC16A1
Ontologies - Pathways
Ontology : AmiGOmitochondrion  centrosome  plasma membrane  plasma membrane  integral component of plasma membrane  integral component of plasma membrane  pyruvate metabolic process  blood coagulation  monocarboxylic acid transmembrane transporter activity  mevalonate transmembrane transporter activity  symporter activity  secondary active monocarboxylate transmembrane transporter activity  monocarboxylic acid transport  mevalonate transport  membrane  integral component of membrane  plasma membrane lactate transport  protein homodimerization activity  cellular metabolic process  small molecule metabolic process  leukocyte migration  centrosome organization  transmembrane transport  extracellular vesicular exosome  cellular response to organic cyclic compound  organic cyclic compound binding  
Ontology : EGO-EBImitochondrion  centrosome  plasma membrane  plasma membrane  integral component of plasma membrane  integral component of plasma membrane  pyruvate metabolic process  blood coagulation  monocarboxylic acid transmembrane transporter activity  mevalonate transmembrane transporter activity  symporter activity  secondary active monocarboxylate transmembrane transporter activity  monocarboxylic acid transport  mevalonate transport  membrane  integral component of membrane  plasma membrane lactate transport  protein homodimerization activity  cellular metabolic process  small molecule metabolic process  leukocyte migration  centrosome organization  transmembrane transport  extracellular vesicular exosome  cellular response to organic cyclic compound  organic cyclic compound binding  
Protein Interaction DatabaseSLC16A1
Wikipedia pathwaysSLC16A1
Gene fusion - rearrangments
Polymorphisms : SNP, mutations, diseases
SNP Single Nucleotide Polymorphism (NCBI)SLC16A1
snp3D : Map Gene to Disease6566
SNP (GeneSNP Utah)SLC16A1
SNP : HGBaseSLC16A1
Genetic variants : HAPMAPSLC16A1
Exome VariantSLC16A1
1000_GenomesSLC16A1 
ICGC programENSG00000155380 
Somatic Mutations in Cancer : COSMICSLC16A1 
CONAN: Copy Number AnalysisSLC16A1 
Mutations and Diseases : HGMDSLC16A1
Mutations and Diseases : intOGenSLC16A1
Genomic VariantsSLC16A1  SLC16A1 [DGVbeta]
dbVarSLC16A1
ClinVarSLC16A1
Pred. of missensesPolyPhen-2  SIFT(SG)  SIFT(JCVI)  Align-GVGD  MutAssessor  Mutanalyser  
Pred. splicesGeneSplicer  Human Splicing Finder  MaxEntScan  
Diseases
OMIM245340    600682    610021   
MedgenSLC16A1
GENETestsSLC16A1
Disease Genetic AssociationSLC16A1
Huge Navigator SLC16A1 [HugePedia]  SLC16A1 [HugeCancerGEM]
General knowledge
Homologs : HomoloGeneSLC16A1
Homology/Alignments : Family Browser (UCSC)SLC16A1
Phylogenetic Trees/Animal Genes : TreeFamSLC16A1
Chemical/Protein Interactions : CTD6566
Chemical/Pharm GKB GenePA35813
Clinical trialSLC16A1
Cancer Resource (Charite)ENSG00000155380
Other databases
Probes
Litterature
PubMed98 Pubmed reference(s) in Entrez
CoreMineSLC16A1
iHOPSLC16A1
OncoSearchSLC16A1

Bibliography

cDNA cloning of the human monocarboxylate transporter 1 and chromosomal localization of the SLC16A1 locus to 1p13.2-p12.
Garcia CK, Li X, Luna J, Francke U.
Genomics. 1994 Sep 15;23(2):500-3.
PMID 7835905
 
Cardiac and skeletal muscle mitochondria have a monocarboxylate transporter MCT1.
Brooks GA, Brown MA, Butz CE, Sicurello JP, Dubouchaud H.
J Appl Physiol. 1999 Nov;87(5):1713-8.
PMID 10562613
 
Mutations in MCT1 cDNA in patients with symptomatic deficiency in lactate transport.
Merezhinskaya N, Fishbein WN, Davis JI, Foellmer JW.
Muscle Nerve. 2000 Jan;23(1):90-7.
PMID 10590411
 
The human monocarboxylate transporter, MCT1: genomic organization and promoter analysis.
Cuff MA, Shirazi-Beechey SP.
Biochem Biophys Res Commun. 2002 Apr 12;292(4):1048-56.
PMID 11944921
 
Molecular changes in the expression of human colonic nutrient transporters during the transition from normality to malignancy.
Lambert DW, Wood IS, Ellis A, Shirazi-Beechey SP.
Br J Cancer. 2002 Apr 22;86(8):1262-9.
PMID 11953883
 
Reduced expression of GNA11 and silencing of MCT1 in human breast cancers.
Asada K, Miyamoto K, Fukutomi T, Tsuda H, Yagi Y, Wakazono K, Oishi S, Fukui H, Sugimura T, Ushijima T.
Oncology. 2003;64(4):380-8.
PMID 12759536
 
Peroxisomal membrane monocarboxylate transporters: evidence for a redox shuttle system?
McClelland GB, Khanna S, Gonzalez GF, Butz CE, Brooks GA.
Biochem Biophys Res Commun. 2003 Apr 25;304(1):130-5.
PMID 12705896
 
The SLC16 gene family-from monocarboxylate transporters (MCTs) to aromatic amino acid transporters and beyond.
Halestrap AP, Meredith D.
Pflugers Arch. 2004 Feb;447(5):619-28. Epub 2003 May 9. (REVIEW)
PMID 12739169
 
Silencing of monocarboxylate transporters via small interfering ribonucleic acid inhibits glycolysis and induces cell death in malignant glioma: an in vitro study.
Mathupala SP, Parajuli P, Sloan AE.
Neurosurgery. 2004 Dec;55(6):1410-9; discussion 1419.
PMID 15574223
 
The H+-linked monocarboxylate transporter (MCT1/SLC16A1): a potential therapeutic target for high-risk neuroblastoma.
Fang J, Quinones QJ, Holman TL, Morowitz MJ, Wang Q, Zhao H, Sivo F, Maris JM, Wahl ML.
Mol Pharmacol. 2006 Dec;70(6):2108-15. Epub 2006 Sep 25.
PMID 17000864
 
Comparison of metabolic pathways between cancer cells and stromal cells in colorectal carcinomas: a metabolic survival role for tumor-associated stroma.
Koukourakis MI, Giatromanolaki A, Harris AL, Sivridis E.
Cancer Res. 2006 Jan 15;66(2):632-7.
PMID 16423989
 
Lung cancer: a comparative study of metabolism related protein expression in cancer cells and tumor associated stroma.
Koukourakis MI, Giatromanolaki A, Bougioukas G, Sivridis E.
Cancer Biol Ther. 2007 Sep;6(9):1476-9. Epub 2007 Jun 27.
PMID 17881895
 
Physical exercise-induced hypoglycemia caused by failed silencing of monocarboxylate transporter 1 in pancreatic beta cells.
Otonkoski T, Jiao H, Kaminen-Ahola N, Tapia-Paez I, Ullah MS, Parton LE, Schuit F, Quintens R, Sipila I, Mayatepek E, Meissner T, Halestrap AP, Rutter GA, Kere J.
Am J Hum Genet. 2007 Sep;81(3):467-74. Epub 2007 Jul 26.
PMID 17701893
 
Increased expression of monocarboxylate transporters 1, 2, and 4 in colorectal carcinomas.
Pinheiro C, Longatto-Filho A, Scapulatempo C, Ferreira L, Martins S, Pellerin L, Rodrigues M, Alves VA, Schmitt F, Baltazar F.
Virchows Arch. 2008 Feb;452(2):139-46. Epub 2008 Jan 10.
PMID 18188595
 
Increasing expression of monocarboxylate transporters 1 and 4 along progression to invasive cervical carcinoma.
Pinheiro C, Longatto-Filho A, Ferreira L, Pereira SM, Etlinger D, Moreira MA, Jubé LF, Queiroz GS, Schmitt F, Baltazar F.
Int J Gynecol Pathol. 2008 Oct;27(4):568-74.
PMID 18753962
 
The prognostic value of CD147/EMMPRIN is associated with monocarboxylate transporter 1 co-expression in gastric cancer.
Pinheiro C, Longatto-Filho A, Simoes K, Jacob CE, Bresciani CJ, Zilberstein B, Cecconello I, Alves VA, Schmitt F, Baltazar F.
Eur J Cancer. 2009 Sep;45(13):2418-24. Epub 2009 Jul 21.
PMID 19628385
 
Monocarboxylate transporter 1 is upregulated in basal-like breast carcinoma.
Pinheiro C, Albergaria A, Paredes J, Sousa B, Dufloth R, Vieira D, Schmitt F, Baltazar F.
Histopathology In press
 
REVIEW articlesautomatic search in PubMed
Last year publicationsautomatic search in PubMed

Search in all EBI   NCBI

Contributor(s)

Written02-2010Céline Pinheiro, Fátima Baltazar
Life and Health Sciences Research Institute, School of Health Sciences, University of Minho, Campus of Gualtar, 4710-057 Braga, Portugal

Citation

This paper should be referenced as such :
Pinheiro, C ; Baltazar, F
SLC16A1 (solute carrier family 16, member 1 (monocarboxylic acid transporter 1))
Atlas Genet Cytogenet Oncol Haematol. 2010;14(12):-.
Free online version   Free pdf version   [Bibliographic record ]
URL : http://AtlasGeneticsOncology.org/Genes/SLC16A1ID44046ch1p13.html

© Atlas of Genetics and Cytogenetics in Oncology and Haematology
indexed on : Tue Aug 26 15:28:43 CEST 2014

Home   Genes   Leukemias   Solid Tumours   Cancer-Prone   Deep Insight   Case Reports   Journals  Portal   Teaching   

For comments and suggestions or contributions, please contact us

jlhuret@AtlasGeneticsOncology.org.