SLC45A2 gene

The SLC45A2 gene (SLC45A2 stands for: Solute Carrier Family 45 Member 2) is a protein-coding gene located on chromosome 5p13.2. Several transcript variants encoding different isoforms have been found for this gene. An important paralog of this gene is SLC45A1.

The SLC45A2 gene encodes a transporter protein that mediates melanin synthesis. The protein is also expressed in a high percentage of melanoma cell lines. Mutations in this gene are a cause of oculocutaneous albinism type 4.

SLC45A2 codes for a putative transporter that is mainly expressed in pigment cells. The transporter protein is expressed at a late melanosome maturation stage where it functions as a proton/glucose exporter that increases lumenal pH by reducing glycolysis (Le L et al. 2020). SLC45A2 is ectopically expressed in HeLa cells and is localized in lysosomes. It increases lysosomal pH, suggesting that the expression of SLC45A2 in melanocytes, like the expression of OCA2, leads to a Ph shift in maturing melanosomes, which underpins melanin synthesis. The overexpression of OCA2 compensates for the loss of SLC45A2 expression during pigmentation. Experimental animal analyses of SLC45A2- and OCA2-deficient melanocytes show that SLC45A2 probably acts later during melanosome maturation than OCA2.

The transporter protein also functions as a proton-associated glucose and sucrose transporter. It may also be able to transport fructose. The SLC45A2 protein regulates melanogenesis by maintaining melanosome neutralization, which is initially initiated by transient OCA2 and is required for proper tyrosinase TYR function (Le L et al. 2020)

1. Le L et al. (2020) SLC45A2 protein stability and regulation of melanosome pH determine melanocyte pigmentation. Mol Biol Cell 31:2687-2702.
2. Liu Y et al. (2022) Ablation of Proton/Glucose Exporter SLC45A2 Enhances Melanosomal Glycolysis to Inhibit Melanin Biosynthesis and Promote Melanoma Metastasis. J Invest Dermatol 142:2744-2755.