Introduction of SLC52A3
SLC52A3 (solute carrier family 52 member 3), also known as BVVLS1 or BVVLS, is an approximately 50.8 kDa transmembrane protein that consists of 469 amino acids length. In humans, it is encoded by the SLC52A3 gene localized at the chromosome 20p13. This protein is predicted to contain 11 transmembrane domains (TMDs) and a cell surface localization signal in the COOH-terminus. And this COOH-terminal tail is oriented toward the cell exterior while the NH2-terminal tail toward the cell interior. The SLC52A3 gene codes for a riboflavin transporter protein that is strongly expressed in the small intestine and plays a crucial role in the absorption of riboflavin during digestion.
|Basic Information of SLC52A3|
|Protein Name||Solute carrier family 52, riboflavin transporter, member 3|
|Aliases||Riboflavin transporter 2, hRFT2|
|Organism||Homo sapiens (Human)|
|Transmembrane Times||11 (putative)|
Function of SLC52A3 Membrane Protein
Human SLC52A3 gene encodes a riboflavin transporter protein that moves the Vitamin B2 known as riboflavin across the cell membrane. It has been found to play a significant part in the absorption of riboflavin and the regulation of riboflavin tissue distribution. And in vitro studies imply that this gene functionally participates in the intestinal riboflavin absorption in the apical membranes of intestinal epithelial cells. Notably, it is reported that riboflavin deficiency increases the expression level of SLC52A3, suggesting a negative feedback regulatory mechanism maintaining this riboflavin homeostasis. Recently, mutations in SLC52A3 have been associated with a neurological disorder, Brown-Vialetto-Van Laere (BVVL), wherein fatty acid metabolism is impaired. Based on that, the SLC52A3 disruption may disturb riboflavin homeostasis and trigger BVVLS syndrome. In addition, SLC52A3 is believed to be involved in the biology of certain tumor types, including those from cervix and stomach and has been identified it as both a predictive and prognostic biomarker for esophageal squamous cell cancers (ESSC).
Fig.1 (A) The predicted membrane topology of human riboflavin transporter-3 (hRFVT-3). (Subramanian, 2017); (B) Mechanism of riboflavin absorption in mouse placenta. (Intoh, 2016)
Application of SLC52A3 Membrane Protein in Literature
This study reveals that SLC52A3 has two transcript variants encoding different proteins, SLC52A3a and SLC52A3b. Importantly, abnormal expressions of SLC52A3 are correlated with the stepwise development of esophageal squamous cell carcinoma (ESCC) and survival rates of ESCC patients. Finally, SLC52A3 is identified as both a predictive and prognostic biomarker for this cancer.
Mutations in SLC52A2 and SLC52A3, coding for riboflavin transporters RFVT2 and RFVT3 respectively, are the genetic basis of Brown-Vialetto-van Laere syndrome. This article displays cases of two types of riboflavin transporter deficiency, emphasizing distinct clinical features of a rapidly progressive motor, sensorineural hearing loss, optic atrophy, and bulbar dysfunction.
Brown-Vialetto-Van Laere Syndrome is a rare disorder featured by the motor, sensory, and cranial neuronopathies. This article introduces a clinical course of a six-year-old girl with this syndrome and a novel mutation c.1156T>C in the SLC52A3 gene.
The findings in this study indicate that the hRFVT-3 protein is glycosylated and this glycosylation is essential for its function and expression. Furthermore, a number of residues in the hRFVT-3 polypeptide are identified that are significant for its function and cell surface expression.
Previous in vitro research has elucidated basic information regarding riboflavin transporter RFVT3 encoded by SLC52A3 gene. This review is the first report so far to demonstrate that Rfvt3 contributes to placental riboflavin transport and the disruption of Slc52a3 gene causes neonatal mortality with hyperlipidemia and hypoglycemia due to riboflavin deficiency.
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