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SLC16A3 (solute carrier family 16, member 3
(monocarboxylic acid transporter 4))
Céline Pinheiro, Fátima Baltazar
Life and Health Sciences Research Institute (ICVS), School of Health Sciences, University of Minho,
Campus of Gualtar, 4710-057 Braga, Portugal (CP, FB)
Published in Atlas Database: March 2010
Online updated version : http://AtlasGeneticsOncology.org/Genes/SLC16A3ID44573ch17q25.html
DOI: 10.4267/2042/44920
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
cells, chondrocytes, testis, lung, placenta, heart and
some mammalian cell lines (Halestrap and Meredith,
2004; Meredith and Christian, 2008).
Identity
Other names: MCT3,
MGC138474
HGNC (Hugo): SLC16A3
Location: 17q25.3
MCT4,
MGC138472,
Localisation
Plasma membrane.
Function
DNA/RNA
Note
SLC16A3 was first cloned from human circulating
blood by Price et al. (1998).
Proton-linked monocarboxylate transporter. Catalyzes
plasma membrane transport of monocarboxylates such
as lactate, pyruvate, branched-chain oxo acids derived
from leucine, valine and isoleucine, and the ketone
bodies acetoacetate, beta-hydroxybutyrate and acetate.
Description
Homology
11077 bp lenght, 5 exons.
Belongs to the major facilitator superfamily (MFS).
Monocarboxylate porter (TC 2.A.1.13) family. The
SLC16A3 gene is conserved in chimpanzee, dog, cow,
mouse, rat, chicken, zebrafish, and M. grisea.
Transcription
3 transcripts have been described for this gene (all with
protein product): SLC16A3-201, (5 exons; 2033 bps
transcript length; 465 residues translation length);
SLC16A3-202 (4 exons; 4222 bps transcript length;
465 residues translation length); SLC16A3-203 (5
exons; 2054 bps transcript length; 465 residues
translation length).
Implicated in
Colorectal carcinoma
Note
SLC16A3/MCT4 protein is overexpressed in colorectal
cancer (Pinheiro et al., 2008a).
Protein
Cervical cancer
Description
Note
SLC16A3/MCT4 protein is overexpressed in cervical
cancer (Pinheiro et al., 2008b). SLC16A3/MCT4
protein overexpression in cervical cancer correlated
with positivity for high-risk HPV (Pinheiro et al.,
2008b).
465 residues; 49469 Da; 12 transmembrane domains;
intracellular N- and C-terminals.
Expression
SLC16A3/MCT4 is expressed in tissues such as white
skeletal muscle fibres, astrocytes, white blood
Atlas Genet Cytogenet Oncol Haematol. 2010; 14(12)
1157
SLC16A3 (solute carrier family 16, member 3 (monocarboxylic acid transporter 4))
Pinheiro C, Baltazar F
Protein diagram drawn following UniProtKB/Swiss-Prot database prediction, using TMRPres2D software.
a patient with a mitochondrial myopathy (Baker et al.,
2001).
Bladder cancer
Note
SLC16A3 gene expression was upregulated in some
bladder tumours and induced by hypoxia in bladder
cancer cell lines, but not in cultures of normal
urothelium (Ord et al., 2005).
Chronic obstructive pulmonary disease
Note
SLC16A3/MCT4 downregulation was described in the
vastus lateralis muscle of patients with chronic
obstructive pulmonary disease as compared with
healthy controls (Green et al., 2008).
Breast cancer
Note
Induction was also seen in two breast cancer cell lines.
Expression of SLC16A3 gene is higher in breast cancer
distant metastasis as compared to primary tumours or
regional metastasis. SLC16A3 gene was then included
in the 'VEGF profile' of breast cancer, associated with
promotion of vessel formation, survival under
anaerobic conditions and loss of dependence upon
fibroblasts (Hu et al., 2009).
References
Price NT, Jackson VN, Halestrap AP. Cloning and sequencing
of four new mammalian monocarboxylate transporter (MCT)
homologues confirms the existence of a transporter family with
an ancient past. Biochem J. 1998 Jan 15;329 ( Pt 2):321-8
Baker SK, Tarnopolsky MA, Bonen A. Expression of MCT1 and
MCT4 in a patient with mitochondrial myopathy. Muscle Nerve.
2001 Mar;24(3):394-8
Ovarian cancer
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
Note
SLC16A3 gene expression was described to be
downregulated in malignant ovarian tumours as
compared to normal ovarian surface epithelial cells.
Additionally, the non-tumorigenic cell line TOV-81D
presented higher expression that tumorigenic cell lines
(Wojnarowicz et al., 2008).
SLC16A3 gene, among other transporter genes, was
differentially expressed in a chemotherapy resistant
ovarian cancer cell line and tumour tissue as compared
to a chemosensitive cell line and tumour tissue. It was
suggested that these transporters might be involved in
drug influx/efflux, modulating chemotherapy response
(Cheng et al., 2010).
Ord JJ, Streeter EH, Roberts IS, Cranston D, Harris AL.
Comparison of hypoxia transcriptome in vitro with in vivo gene
expression in human bladder cancer. Br J Cancer. 2005 Aug
8;93(3):346-54
Green HJ, Burnett ME, D'Arsigny CL, O'Donnell DE, Ouyang J,
Webb KA. Altered metabolic and transporter characteristics of
vastus lateralis in chronic obstructive pulmonary disease. J
Appl Physiol. 2008 Sep;105(3):879-86
Meredith D, Christian HC. The SLC16 monocaboxylate
transporter family. Xenobiotica. 2008 Jul;38(7-8):1072-106
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
Mitochondrial myopathy
Note
SLC16A3/MCT4 overexpression was described in
Atlas Genet Cytogenet Oncol Haematol. 2010; 14(12)
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SLC16A3 (solute carrier family 16, member 3 (monocarboxylic acid transporter 4))
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
Perou CM. A compact VEGF signature associated with distant
metastases and poor outcomes. BMC Med. 2009 Mar 16;7:9
Cheng L, Lu W, Kulkarni B, Pejovic T, Yan X, Chiang JH, Hood
L, Odunsi K, Lin B. Analysis of chemotherapy response
programs in ovarian cancers by the next-generation
sequencing
technologies.
Gynecol
Oncol.
2010
May;117(2):159-69
Wojnarowicz PM, Breznan A, Arcand SL, Filali-Mouhim A,
Provencher DM, Mes-Masson AM, Tonin PN. Construction of a
chromosome 17 transcriptome in serous ovarian cancer
identifies differentially expressed genes. Int J Gynecol Cancer.
2008 Sep-Oct;18(5):963-75
This article should be referenced as such:
Pinheiro C, Baltazar F. SLC16A3 (solute carrier family 16,
member 3 (monocarboxylic acid transporter 4)). Atlas Genet
Cytogenet Oncol Haematol. 2010; 14(12):1157-1159.
Hu Z, Fan C, Livasy C, He X, Oh DS, Ewend MG, Carey LA,
Subramanian S, West R, Ikpatt F, Olopade OI, van de Rijn M,
Atlas Genet Cytogenet Oncol Haematol. 2010; 14(12)
Pinheiro C, Baltazar F
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