Download Gene Section SLC16A1 (solute carrier family 16, member 1

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Gene Section
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SLC16A1 (solute carrier family 16, member 1
(monocarboxylic acid transporter 1))
Céline Pinheiro, Fátima Baltazar
Life and Health Sciences Research Institute, School of Health Sciences, University of Minho, Campus of
Gualtar, 4710-057 Braga, Portugal (CP, FB)
Published in Atlas Database: February 2010
Online updated version : http://AtlasGeneticsOncology.org/Genes/SLC16A1ID44046ch1p13.html
DOI: 10.4267/2042/44910
This work is licensed under a Creative Commons Attribution-Noncommercial-No Derivative Works 2.0 France Licence.
© 2010 Atlas of Genetics and Cytogenetics in Oncology and Haematology
Pseudogene
Identity
1 related pseudogene identified - AKR7 family
pseudogene (AFARP1), non-coding RNA.
Other names: FLJ36745, HHF7, MCT, MCT1,
MGC44475
HGNC (Hugo): SLC16A1
Location: 1p13.2
Protein
Description
DNA/RNA
500 amino acids; 53958 Da; 12 transmembrane
domains, intracellular N- and C-terminal and a large
intracellular loop between transmembrane domains 6
and 7.
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.
Expression
Ubiquitous.
Description
Localisation
44507 bp lenght, containing 5 exons. Various SNPs
have been described in SLC16A1 gene.
Plasma membrane; also described in rat mitochondrial
and peroxisomal membranes.
Transcription
Function
6 transcripts have been described for this gene (4 with
protein product, 2 with no protein product): SLC16A1001 (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).
Atlas Genet Cytogenet Oncol Haematol. 2010; 14(12)
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, betahydroxybutyrate 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.
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SLC16A1 (solute carrier family 16, member 1 (monocarboxylic acid transporter 1))
Pinheiro C, Baltazar F
Protein diagram drawn following UniProtKB/Swiss-Prot database prediction, using TMRPres2D software.
associated with advanced gastric carcinoma,
Lauren's intestinal type, TNM staging and lymph-node
metastasis, in gastric cancer.
Implicated in
Various cancers
Colorectal carcinoma
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).
Note
MCT1/SLC16A1 has been described to be
downregulated in colorectal carcinoma (Lamber et al.,
2002).
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 Cterminal 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.
Breast cancer
Prognosis
In breast cancer, MCT1/SLC16A1 was found to be
associated with poor prognostic variables such as basallike 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).
Hyperinsulinemic hypoglycemia familial
7
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
Atlas Genet Cytogenet Oncol Haematol. 2010; 14(12)
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
1116
SLC16A1 (solute carrier family 16, member 1 (monocarboxylic acid transporter 1))
Pinheiro C, Baltazar F
Mathupala SP, Parajuli P, Sloan AE. Silencing of
monocarboxylate transporters via small interfering ribonucleic
acid inhibits glycolysis and induces cell death in malignant
glioma: an in vitro study. Neurosurgery. 2004 Dec;55(6):14109; discussion 1419
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 10fold increase in transcription. These mutations were not
found in 92 Finnish and German controls.
Fang J, Quinones QJ, Holman TL, Morowitz MJ, Wang Q,
Zhao H, Sivo F, Maris JM, Wahl ML. The H+-linked
monocarboxylate transporter (MCT1/SLC16A1): a potential
therapeutic target for high-risk neuroblastoma. Mol Pharmacol.
2006 Dec;70(6):2108-15
References
Pinheiro C, Albergaria A, Paredes J, Sousa B, Dufloth R, Vieira
D, Schmitt F, Baltazar F.. Monocarboxylate transporter 1 is
upregulated in basal-like breast carcinoma. Histopathology In
press
Koukourakis MI, Giatromanolaki A, Harris AL, Sivridis E.
Comparison of metabolic pathways between cancer cells and
stromal cells in colorectal carcinomas: a metabolic survival role
for tumor-associated stroma. Cancer Res. 2006 Jan
15;66(2):632-7
Garcia CK, Li X, Luna J, Francke U. cDNA cloning of the
human monocarboxylate transporter 1 and chromosomal
localization of the SLC16A1 locus to 1p13.2-p12. Genomics.
1994 Sep 15;23(2):500-3
Koukourakis MI, Giatromanolaki A, Bougioukas G, Sivridis E.
Lung cancer: a comparative study of metabolism related
protein expression in cancer cells and tumor associated
stroma. Cancer Biol Ther. 2007 Sep;6(9):1476-9
Brooks GA, Brown MA, Butz CE, Sicurello JP, Dubouchaud H.
Cardiac and skeletal muscle mitochondria have a
monocarboxylate transporter MCT1. J Appl Physiol. 1999
Nov;87(5):1713-8
Otonkoski T, Jiao H, Kaminen-Ahola N, Tapia-Paez I, Ullah
MS, Parton LE, Schuit F, Quintens R, Sipilä I, Mayatepek E,
Meissner T, Halestrap AP, Rutter GA, Kere J. Physical
exercise-induced hypoglycemia caused by failed silencing of
monocarboxylate transporter 1 in pancreatic beta cells. Am J
Hum Genet. 2007 Sep;81(3):467-74
Merezhinskaya N, Fishbein WN, Davis JI, Foellmer JW.
Mutations in MCT1 cDNA in patients with symptomatic
deficiency in lactate transport. Muscle Nerve. 2000
Jan;23(1):90-7
Pinheiro C, Longatto-Filho A, Ferreira L, Pereira SM, Etlinger
D, Moreira MA, Jubé LF, Queiroz GS, Schmitt F, Baltazar F.
Increasing expression of monocarboxylate transporters 1 and 4
along progression to invasive cervical carcinoma. Int J Gynecol
Pathol. 2008 Oct;27(4):568-74
Cuff MA, Shirazi-Beechey SP. The human monocarboxylate
transporter, MCT1: genomic organization and promoter
analysis. Biochem Biophys Res Commun. 2002 Apr
12;292(4):1048-56
Pinheiro C, Longatto-Filho A, Scapulatempo C, Ferreira L,
Martins S, Pellerin L, Rodrigues M, Alves VA, Schmitt F,
Baltazar F. Increased expression of monocarboxylate
transporters 1, 2, and 4 in colorectal carcinomas. Virchows
Arch. 2008 Feb;452(2):139-46
Lambert DW, Wood IS, Ellis A, Shirazi-Beechey SP. Molecular
changes in the expression of human colonic nutrient
transporters during the transition from normality to malignancy.
Br J Cancer. 2002 Apr 22;86(8):1262-9
Pinheiro C, Longatto-Filho A, Simões K, Jacob CE, Bresciani
CJ, Zilberstein B, Cecconello I, Alves VA, Schmitt F, Baltazar
F. The prognostic value of CD147/EMMPRIN is associated
with monocarboxylate transporter 1 co-expression in gastric
cancer. Eur J Cancer. 2009 Sep;45(13):2418-24
Asada K, Miyamoto K, Fukutomi T, Tsuda H, Yagi Y,
Wakazono K, Oishi S, Fukui H, Sugimura T, Ushijima T.
Reduced expression of GNA11 and silencing of MCT1 in
human breast cancers. Oncology. 2003;64(4):380-8
McClelland GB, Khanna S, González GF, Butz CE, Brooks GA.
Peroxisomal membrane monocarboxylate transporters:
evidence for a redox shuttle system? Biochem Biophys Res
Commun. 2003 Apr 25;304(1):130-5
This article 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):1115-1117.
Halestrap AP, Meredith D. The SLC16 gene family-from
monocarboxylate transporters (MCTs) to aromatic amino acid
transporters and beyond. Pflugers Arch. 2004 Feb;447(5):61928
Atlas Genet Cytogenet Oncol Haematol. 2010; 14(12)
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