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| | Protein diagram drawn following UniProtKB/Swiss-Prot database prediction, using TMRPres2D software. |
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| 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. |
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| Entity | Colorectal carcinoma |
| Note | SLC16A3/MCT4 protein is overexpressed in colorectal cancer (Pinheiro et al., 2008a). |
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| Entity | 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). |
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| Entity | 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). |
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| Entity | 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). |
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| Entity | 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). |
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| Entity | Mitochondrial myopathy |
| Note | SLC16A3/MCT4 overexpression was described in a patient with a mitochondrial myopathy (Baker et al., 2001). |
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| Entity | 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). |
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| Expression of MCT1 and MCT4 in a patient with mitochondrial myopathy. |
| Baker SK, Tarnopolsky MA, Bonen A. |
| Muscle Nerve. 2001 Mar;24(3):394-8. |
| PMID 11353425 |
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| Analysis of chemotherapy response programs in ovarian cancers by the next-generation sequencing technologies. |
| Cheng L, Lu W, Kulkarni B, Pejovic T, Yan X, Chiang JH, Hood L, Odunsi K, Lin B. |
| Gynecol Oncol. 2010 Feb 22. [Epub ahead of print] |
| PMID 20181382 |
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| Altered metabolic and transporter characteristics of vastus lateralis in chronic obstructive pulmonary disease. |
| Green HJ, Burnett ME, D'Arsigny CL, O'Donnell DE, Ouyang J, Webb KA. |
| J Appl Physiol. 2008 Sep;105(3):879-86. Epub 2008 Jul 17. |
| PMID 18635880 |
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| 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. |
| PMID 12739169 |
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| A compact VEGF signature associated with distant metastases and poor outcomes. |
| 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, Perou CM. |
| BMC Med. 2009 Mar 16;7:9. |
| PMID 19291283 |
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| The SLC16 monocaboxylate transporter family. |
| Meredith D, Christian HC. |
| Xenobiotica. 2008 Jul;38(7-8):1072-106. (REVIEW) |
| PMID 18668440 |
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| Comparison of hypoxia transcriptome in vitro with in vivo gene expression in human bladder cancer. |
| Ord JJ, Streeter EH, Roberts IS, Cranston D, Harris AL. |
| Br J Cancer. 2005 Aug 8;93(3):346-54. |
| PMID 16052224 |
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| 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, Jube LF, Queiroz GS, Schmitt F, Baltazar F. |
| Int J Gynecol Pathol. 2008b Oct;27(4):568-74. |
| PMID 18753962 |
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| Cloning and sequencing of four new mammalian monocarboxylate transporter (MCT) homologues confirms the existence of a transporter family with an ancient past. |
| Price NT, Jackson VN, Halestrap AP. |
| Biochem J. 1998 Jan 15;329 ( Pt 2):321-8. |
| PMID 9425115 |
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| Construction of a chromosome 17 transcriptome in serous ovarian cancer identifies differentially expressed genes. |
| Wojnarowicz PM, Breznan A, Arcand SL, Filali-Mouhim A, Provencher DM, Mes-Masson AM, Tonin PN. |
| Int J Gynecol Cancer. 2008 Sep-Oct;18(5):963-75. Epub 2007 Nov 20. |
| PMID 18028382 |
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