The homo-sapiens solute carrier family 2 member 14 (SLC2A14) – further insight into the genomic organization, protein isoforms, substrates and kinetics

Abstract

The SLC2A14 gene encodes for GLUT14, a novel glucose and dehydroascorbic acid facilitative solute carrier. The literature record on SLC2A14 and its encoded products are very limited. To date, two different transcripts encoding for two protein isoforms had been described. Genetic variations in SLC2A14 are associated with chronic diseases such as Alzheimer’s disease and Inflammatory Bowel Disease. However, disease mechanism concerning glucose metabolism are undetermined. To investigate disease mechanism, all genomic transcripts and protein isoforms need to be annotated. Our objectives were to describe the SLC2A14 locus and its encoded products systematically using recent bioinformatics resources and link the gained knowledge to potential disease pathology. Three manuscripts were derived. In manuscript 1, novel transcripts and individual protein isoforms were identified and annotated. A much more comprehensive list of tissues expressing SLC2A14 was created. All protein isoforms were heterologous expressed in human enterocyte cells to determine subcellular localization to the plasmalemma membrane. In manuscript 2, the substrate spectrum and kinetics were determined for protein isoform GLUT14A. In manuscript 3, SLC2A14’s association to inflammatory bowel diseases was linked to the modulation of innate immune cells based on the expression evidence in intestinal cell types. The project establishes the core SLC2A14 biology. This will form the basis to further investigate the disease mechanism associated with SLC2A14 genetic and genomic variability.