SLC16A3 (solute carrier family 16, member 3 (monocarboxylic acid transporter 4))

2010-03-01   Céline Pinheiro , Fátima Baltazar 

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

Identity

HGNC
LOCATION
17q25.3
LOCUSID
ALIAS
MCT
FUSION GENES

DNA/RNA

Note

SLC16A3 was first cloned from human circulating blood by Price et al. (1998).

Description

11077 bp lenght, 5 exons.

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).

Proteins

Atlas Image
Protein diagram drawn following UniProtKB/Swiss-Prot database prediction, using TMRPres2D software.

Description

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 cells, chondrocytes, testis, lung, placenta, heart and some mammalian cell lines (Halestrap and Meredith, 2004; Meredith and Christian, 2008).

Localisation

Plasma membrane.

Function

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.

Homology

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.

Implicated in

Entity name
Colorectal carcinoma
Note
SLC16A3/MCT4 protein is overexpressed in colorectal cancer (Pinheiro et al., 2008a).
Entity name
Cervical cancer
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).
Entity name
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).
Entity name
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).
Entity name
Ovarian cancer
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).
Entity name
Mitochondrial myopathy
Note
SLC16A3/MCT4 overexpression was described in a patient with a mitochondrial myopathy (Baker et al., 2001).
Entity name
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).

Bibliography

Pubmed IDLast YearTitleAuthors
113534252001Expression of MCT1 and MCT4 in a patient with mitochondrial myopathy.Baker SK et al
201813822010Analysis of chemotherapy response programs in ovarian cancers by the next-generation sequencing technologies.Cheng L et al
186358802008Altered metabolic and transporter characteristics of vastus lateralis in chronic obstructive pulmonary disease.Green HJ et al
127391692004The SLC16 gene family-from monocarboxylate transporters (MCTs) to aromatic amino acid transporters and beyond.Halestrap AP et al
192912832009A compact VEGF signature associated with distant metastases and poor outcomes.Hu Z et al
186684402008The SLC16 monocaboxylate transporter family.Meredith D et al
160522242005Comparison of hypoxia transcriptome in vitro with in vivo gene expression in human bladder cancer.Ord JJ et al
187539622008Increasing expression of monocarboxylate transporters 1 and 4 along progression to invasive cervical carcinoma.Pinheiro C et al
94251151998Cloning and sequencing of four new mammalian monocarboxylate transporter (MCT) homologues confirms the existence of a transporter family with an ancient past.Price NT et al
180283822008Construction of a chromosome 17 transcriptome in serous ovarian cancer identifies differentially expressed genes.Wojnarowicz PM et al

Other Information

Locus ID:

NCBI: 9123
MIM: 603877
HGNC: 10924
Ensembl: ENSG00000141526

Variants:

dbSNP: 9123
ClinVar: 9123
TCGA: ENSG00000141526
COSMIC: SLC16A3

RNA/Proteins

Gene IDTranscript IDUniprot
ENSG00000141526ENST00000392339O15427
ENSG00000141526ENST00000392339A0A024R8U1
ENSG00000141526ENST00000392341O15427
ENSG00000141526ENST00000392341A0A024R8U1
ENSG00000141526ENST00000577650J3KTM6
ENSG00000141526ENST00000578522J3QLE3
ENSG00000141526ENST00000578684J3QQV2
ENSG00000141526ENST00000580098J3QQS9
ENSG00000141526ENST00000580189J3QRA0
ENSG00000141526ENST00000581287O15427
ENSG00000141526ENST00000581287A0A024R8U1
ENSG00000141526ENST00000582715J3QRP8
ENSG00000141526ENST00000582743O15427
ENSG00000141526ENST00000582743A0A024R8U1
ENSG00000141526ENST00000582946J3QRU2
ENSG00000141526ENST00000583025J3KTI8
ENSG00000141526ENST00000583237J3KT83
ENSG00000141526ENST00000584689J3QSC3
ENSG00000141526ENST00000617373O15427
ENSG00000141526ENST00000617373A0A024R8U1
ENSG00000141526ENST00000619321O15427
ENSG00000141526ENST00000619321A0A024R8U1

Expression (GTEx)

0
50
100
150
200

Pathways

PathwaySourceExternal ID
Central carbon metabolism in cancerKEGGhsa05230
Central carbon metabolism in cancerKEGGko05230
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
199131212009Gene-centric association signals for lipids and apolipoproteins identified via the HumanCVD BeadChip.85
175023412007The role of monocarboxylate transporter 2 and 4 in the transport of gamma-hydroxybutyric acid in mammalian cells.24
206280862010Variation at the NFATC2 locus increases the risk of thiazolidinedione-induced edema in the Diabetes REduction Assessment with ramipril and rosiglitazone Medication (DREAM) study.11
200358632010Monocarboxylate transport in human corneal epithelium and cell lines.7
268547232016Butyric acid increases transepithelial transport of ferulic acid through upregulation of the monocarboxylate transporters SLC16A1 (MCT1) and SLC16A3 (MCT4).6
300516482018Downregulation of MCT4 for lactate exchange promotes the cytotoxicity of NK cells in breast carcinoma.6

Citation

Céline Pinheiro ; Fátima Baltazar

SLC16A3 (solute carrier family 16, member 3 (monocarboxylic acid transporter 4))

Atlas Genet Cytogenet Oncol Haematol. 2010-03-01

Online version: http://atlasgeneticsoncology.org/gene/44573/slc16a3