SLC16A12 Membrane Protein Introduction

Introduction of SLC16A12

SLC16A12 is also known as Monocarboxylate transporter 12 (MCT 12), Creatine transporter 2 (CRT2) and Solute carrier family 16 member 12. It belongs to the solute carrier family 16 member, SLC16 (or monocarboxylate transporter, MCT) family which shares characteristic sequence motifs. Meanwhile, the structure analysis indicates that SLC16A12 contains 12 transmembrane helices (TMs) with intracellular C- and N-termini and a large cytosolic loop between TMs 6 and 7. Meanwhile, SLC16A12 is also known as orphan transporter because its ligands have not been identified so far.

Function of SLC16A12 Membrane Protein

Based on the mutation analysis, the Monocarboxylate transporter 12 (MCT12) is likely to play a role in energy metabolism, since a premature termination codon in the gene SLC16A12 causes cataracts of the human lens and glucosuria with elevated and non-diabetic glucose levels in urine. In rats, SLC16A12 knockout (KO) animals did neither phenocopy the cataract nor the glucosuria phenotype, however, creatine levels in the urine were significantly elevated. KO male rats accumulated 5.85 mM creatine compared with 1.76 mM in age-matched heterozygous KO males, which corresponds to a ∼3-fold difference. Likewise, a ∼2-fold difference was measured in female rats with 2.12 mM creatine in KO animals versus 1.01 mM in age-matched wild-type siblings. Loss of SLC16A12 results in the retention of creatine in the urine and a single copy of the gene is sufficient for creatine transport. SLC16A12 is also reported to be involved in the establishment and/or maintenance of homeostasis in the lens and probably also in the kidney

Fig.1 Proposed structure of SLC16A12 membrane protein. (Halestrap, 2013)

Application of SLC16A12 Membrane Protein in Literature

1. Abplanalp J., et al. The cataract and glucosuria associated monocarboxylate transporter MCT12 is a new creatine transporter. Hum. Mol. Genet. 2013, 22(16):3218-3226. PubMed ID: 23578822
   
   

   This article reports that a non-synonymous alteration in MCT12 (p.G407S) found in a patient with age-related cataract (ARC) leads to a significant reduction of creatine transport. Furthermore, SLC16A12 knockout (KO) rats have elevated creatine levels in urine.

2. Kloeckener-Gruissem B., et al. Mutation of Solute Carrier SLC16A12 Associates with a Syndrome Combining Juvenile Cataract with Microcornea and Renal Glucosuria. Am. J. Hum. Genet. 2008, 82(3):772-779. PubMed ID: 18304496
   
   

   This article reveals that SLC16A12 is important for lens and kidney homeostasis and discusses its potential role in age-related cataract.

3. Castorino J.J., et al. Juvenile Cataract-Associated Mutation of Solute Carrier SLC16A12 Impairs Trafficking of the Protein to the Plasma Membrane. Investigative Ophthalmology & Visual Science. 2011, 52(9):6774-6784. PubMed ID: 21778275
   
   

   Authors in this article built a model whereby the SLC16A12 (c.643C>T) mutation causes juvenile cataract by a defect in protein trafficking rather than by haploinsufficiency and MCT12 was identified as another MCT isoform that requires CD147 for trafficking to the cell surface.

4. Zuercher J., et al. Alterations of the 5′Untranslated Region of SLC16A12 Lead to Age-Related Cataract. Investigative Ophthalmology & Visual Science. 2010, 51(7):3354-3361. PubMed ID: 20181839
   
   

   The authors in this article analyze SLC16A12 transcripts in surrogate tissue to demonstrate that the monocarboxylate transporter SLC16A12 may contribute to age-related cataract. Sequences within its 5’ UTR modulate translational efficiency with pathogenic consequences.

5. Stäubli A., et al. Abnormal creatine transport of mutations in monocarboxylate transporter 12 (MCT12) found in patients with age-related cataract can be partially rescued by exogenous chaperone CD147. Clinical and Translational Science. 2017, 26(21), 4203-4214. PubMed ID: 29088427
   
   

   This article provides the first insight into the molecular requirements of monocarboxylate transporter 12 (MCT12), with particular emphasis on rescuing effects by its chaperone CD147, which can provide useful pharmacological information for substrate delivery.

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Reference

1. Halestrap AP. (2013) The SLC16 gene family – Structure, role and regulation in health and disease. Molecular Aspects of Medicine. 34(2):337-349.

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