Monocarboxylate transporter 8
| SLC16A2 | |||
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Gene ontology | |||
| Molecular function | |||
| Cellular component | |||
| Biological process | |||
| Sources:Amigo / QuickGO | |||
Ensembl | |||||||||
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| UniProt | |||||||||
| RefSeq (mRNA) | |||||||||
| RefSeq (protein) | |||||||||
| Location (UCSC) | Chr X: 74.42 – 74.53 Mb | Chr X: 102.74 – 102.87 Mb | |||||||
| PubMed search | [3] | [4] | |||||||
| View/Edit Human | View/Edit Mouse |
Monocarboxylate transporter 8 (MCT8) is an active transporter protein that in humans is encoded by the SLC16A2 gene.[5][6][7][8]
Function
MCT8 actively transports a variety of iodo-
Clinical significance
A genetic disorder (discovered in 2003[6] and 2004[9]) is caused by mutation in the transporter of thyroid hormone, MCT8, also known as SLC16A2, is believed to be account for a significant fraction of the undiagnosed neurological disorders (usually resulting in hypotonic/floppy infants with delayed milestones). This genetic defect was known as Allan–Herndon–Dudley syndrome (since 1944) without knowing its actual cause. It has been shown mutated in cases of X-linked leukoencephalopathy.[10] Some of the symptoms for this disorder as are follows: normal to slightly elevated TSH, elevated T3 and reduced T4 (ratio of T3/T4 is about double its normal value). Normal looking at birth and for the first few years, hypotonic (floppy), in particular difficulty to hold the head, possibly difficulty to thrive, possibly with delayed myelination (if so, some cases are reported with an MRI pattern similar to Pelizaeus–Merzbacher disease, known as PMD[11]), possibly with decreased mitochondrial enzyme activities, possibly with fluctuating lactate level. Patients have an alert face, a limited IQ, patients may never talk/walk, 50% need feeding tube, patients have a normal life span. This disease can be ruled out with a simple TSH/T4/T3 thyroid test.
Model organisms
Zebrafish
A knockout
Xenopus
Expression of mct8 has been characterised in
See also
References
- ^ a b c GRCh38: Ensembl release 89: ENSG00000147100 – Ensembl, May 2017
- ^ a b c GRCm38: Ensembl release 89: ENSMUSG00000033965 – Ensembl, May 2017
- ^ "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
- ^ "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
- PMID 7981683.
- ^ PMID 12871948.
- PMID 15889350.
- ^ "Entrez Gene: SLC16A2 solute carrier family 16, member 2 (monocarboxylic acid transporter 8)".
- PMID 14661163.
- S2CID 1157351.
- S2CID 27740314.
- PMID 25255244.
- PMID 25255244.
- PMID 28591769.
- PMID 20417208.
Further reading
- Halestrap AP, Meredith D (Feb 2004). "The SLC16 gene family-from monocarboxylate transporters (MCTs) to aromatic amino acid transporters and beyond". Pflügers Archiv. 447 (5): 619–28. S2CID 15498611.
- Friesema EC, Jansen J, Heuer H, Trajkovic M, Bauer K, Visser TJ (Sep 2006). "Mechanisms of disease: psychomotor retardation and high T3 levels caused by mutations in monocarboxylate transporter 8". Nature Clinical Practice Endocrinology & Metabolism. 2 (9): 512–23. S2CID 25232696.
- Grüters A (2007). "Thyroid hormone transporter defects". Endocrine Development. 10: 118–26. PMID 17684393.
- Andersson B, Wentland MA, Ricafrente JY, Liu W, Gibbs RA (Apr 1996). "A "double adaptor" method for improved shotgun library construction". Analytical Biochemistry. 236 (1): 107–13. PMID 8619474.
- Yu W, Andersson B, Worley KC, Muzny DM, Ding Y, Liu W, Ricafrente JY, Wentland MA, Lennon G, Gibbs RA (Apr 1997). "Large-scale concatenation cDNA sequencing". Genome Research. 7 (4): 353–8. PMID 9110174.
- Price NT, Jackson VN, Halestrap AP (Jan 1998). "Cloning and sequencing of four new mammalian monocarboxylate transporter (MCT) homologues confirms the existence of a transporter family with an ancient past". The Biochemical Journal. 329 (2): 321–8. PMID 9425115.
- Debrand E, Heard E, Avner P (Mar 1998). "Cloning and localization of the murine Xpct gene: evidence for complex rearrangements during the evolution of the region around the Xist gene". Genomics. 48 (3): 296–303. PMID 9545634.
- Dumitrescu AM, Liao XH, Best TB, Brockmann K, Refetoff S (Jan 2004). "A novel syndrome combining thyroid and neurological abnormalities is associated with mutations in a monocarboxylate transporter gene". American Journal of Human Genetics. 74 (1): 168–75. PMID 14661163.
- Friesema EC, Grueters A, Biebermann H, Krude H, von Moers A, Reeser M, Barrett TG, Mancilla EE, Svensson J, Kester MH, Kuiper GG, Balkassmi S, Uitterlinden AG, Koehrle J, Rodien P, Halestrap AP, Visser TJ (2004). "Association between mutations in a thyroid hormone transporter and severe X-linked psychomotor retardation". Lancet. 364 (9443): 1435–7. S2CID 37520843.
- Heuer H, Maier MK, Iden S, Mittag J, Friesema EC, Visser TJ, Bauer K (Apr 2005). "The monocarboxylate transporter 8 linked to human psychomotor retardation is highly expressed in thyroid hormone-sensitive neuron populations". Endocrinology. 146 (4): 1701–6. PMID 15661862.
- Brockmann K, Dumitrescu AM, Best TT, Hanefeld F, Refetoff S (Jun 2005). "X-linked paroxysmal dyskinesia and severe global retardation caused by defective MCT8 gene". Journal of Neurology. 252 (6): 663–6. S2CID 31994320.
- Friesema EC, Kuiper GG, Jansen J, Visser TJ, Kester MH (Nov 2006). "Thyroid hormone transport by the human monocarboxylate transporter 8 and its rate-limiting role in intracellular metabolism". Molecular Endocrinology. 20 (11): 2761–72. PMID 16887882.
- Olsen JV, Blagoev B, Gnad F, Macek B, Kumar C, Mortensen P, Mann M (Nov 2006). "Global, in vivo, and site-specific phosphorylation dynamics in signaling networks". Cell. 127 (3): 635–48. S2CID 7827573.
- Jansen J, Friesema EC, Kester MH, Milici C, Reeser M, Grüters A, Barrett TG, Mancilla EE, Svensson J, Wemeau JL, Busi da Silva Canalli MH, Lundgren J, McEntagart ME, Hopper N, Arts WF, Visser TJ (Jun 2007). "Functional analysis of monocarboxylate transporter 8 mutations identified in patients with X-linked psychomotor retardation and elevated serum triiodothyronine". The Journal of Clinical Endocrinology and Metabolism. 92 (6): 2378–81. PMID 17356046.