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

2010-02-01   Céline Pinheiro , Fátima Baltazar 

Life, Health Sciences Research Institute, School of Health Sciences, University of Minho, Campus of Gualtar, 4710-057 Braga, Portugal

Identity

HGNC
LOCATION
1p13.2
LOCUSID
ALIAS
HHF7,MCT,MCT1,MCT1D
FUSION GENES

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.

Proteins

Atlas Image
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 name
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 name
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 name
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, Laurens intestinal type, TNM staging and lymph-node metastasis, in gastric cancer.
Entity name
Colorectal carcinoma
Note
MCT1/SLC16A1 has been described to be downregulated in colorectal carcinoma (Lamber et al., 2002).
Entity name
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 name
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.

Bibliography

Pubmed IDLast YearTitleAuthors
127595362003Reduced expression of GNA11 and silencing of MCT1 in human breast cancers.Asada K et al
105626131999Cardiac and skeletal muscle mitochondria have a monocarboxylate transporter MCT1.Brooks GA et al
119449212002The human monocarboxylate transporter, MCT1: genomic organization and promoter analysis.Cuff MA et al
170008642006The H+-linked monocarboxylate transporter (MCT1/SLC16A1): a potential therapeutic target for high-risk neuroblastoma.Fang J et al
78359051994cDNA cloning of the human monocarboxylate transporter 1 and chromosomal localization of the SLC16A1 locus to 1p13.2-p12.Garcia CK et al
127391692004The SLC16 gene family-from monocarboxylate transporters (MCTs) to aromatic amino acid transporters and beyond.Halestrap AP et al
178818952007Lung cancer: a comparative study of metabolism related protein expression in cancer cells and tumor associated stroma.Koukourakis MI et al
119538832002Molecular changes in the expression of human colonic nutrient transporters during the transition from normality to malignancy.Lambert DW et al
155742232004Silencing of monocarboxylate transporters via small interfering ribonucleic acid inhibits glycolysis and induces cell death in malignant glioma: an in vitro study.Mathupala SP et al
127058962003Peroxisomal membrane monocarboxylate transporters: evidence for a redox shuttle system?McClelland GB et al
105904112000Mutations in MCT1 cDNA in patients with symptomatic deficiency in lactate transport.Merezhinskaya N et al
177018932007Physical exercise-induced hypoglycemia caused by failed silencing of monocarboxylate transporter 1 in pancreatic beta cells.Otonkoski T et al

Other Information

Locus ID:

NCBI: 6566
MIM: 600682
HGNC: 10922
Ensembl: ENSG00000155380

Variants:

dbSNP: 6566
ClinVar: 6566
TCGA: ENSG00000155380
COSMIC: SLC16A1

RNA/Proteins

Gene IDTranscript IDUniprot
ENSG00000155380ENST00000369626P53985
ENSG00000155380ENST00000369626A0A024R0H1
ENSG00000155380ENST00000429288Q5T8R4
ENSG00000155380ENST00000443580Q5T8R3
ENSG00000155380ENST00000458229Q5T8R5
ENSG00000155380ENST00000538576P53985
ENSG00000155380ENST00000538576A0A024R0H1

Expression (GTEx)

0
10
20
30
40
50
60
70

Pathways

PathwaySourceExternal ID
HemostasisREACTOMER-HSA-109582
Cell surface interactions at the vascular wallREACTOMER-HSA-202733
Basigin interactionsREACTOMER-HSA-210991
Transmembrane transport of small moleculesREACTOMER-HSA-382551
SLC-mediated transmembrane transportREACTOMER-HSA-425407
Transport of glucose and other sugars, bile salts and organic acids, metal ions and amine compoundsREACTOMER-HSA-425366
Proton-coupled monocarboxylate transportREACTOMER-HSA-433692
MetabolismREACTOMER-HSA-1430728
The citric acid (TCA) cycle and respiratory electron transportREACTOMER-HSA-1428517
Pyruvate metabolism and Citric Acid (TCA) cycleREACTOMER-HSA-71406
Pyruvate metabolismREACTOMER-HSA-70268

Protein levels (Protein atlas)

Not detected
Low
Medium
High

References

Pubmed IDYearTitleCitations
190336632008Targeting lactate-fueled respiration selectively kills hypoxic tumor cells in mice.484
219309172011CD147 subunit of lactate/H+ symporters MCT1 and hypoxia-inducible MCT4 is critical for energetics and growth of glycolytic tumors.137
224280472012Targeting the lactate transporter MCT1 in endothelial cells inhibits lactate-induced HIF-1 activation and tumor angiogenesis.117
216464252011miR-29a and miR-29b contribute to pancreatic beta-cell-specific silencing of monocarboxylate transporter 1 (Mct1).93
199131212009Gene-centric association signals for lipids and apolipoproteins identified via the HumanCVD BeadChip.85
198984822009Genetic variants in TPMT and COMT are associated with hearing loss in children receiving cisplatin chemotherapy.84
181885952008Increased expression of monocarboxylate transporters 1, 2, and 4 in colorectal carcinomas.80
242774492014Activity of the monocarboxylate transporter 1 inhibitor AZD3965 in small cell lung cancer.77
235747252013Cancer metabolism, stemness and tumor recurrence: MCT1 and MCT4 are functional biomarkers of metabolic symbiosis in head and neck cancer.70
204546402010Expression of monocarboxylate transporters 1, 2, and 4 in human tumours and their association with CD147 and CD44.67

Citation

Céline Pinheiro ; Fátima Baltazar

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

Atlas Genet Cytogenet Oncol Haematol. 2010-02-01

Online version: http://atlasgeneticsoncology.org/gene/44046/slc16a1-(solute-carrier-family-16-member-1-(monocarboxylic-acid-transporter-1))