Membrane-associated transporter protein

Function

SLC45A2 is a transporter protein that mediates melanin synthesis. It may regulate the pH of the melanosome, affecting tyrosinase activity. SLC45A2 is also a melanocyte differentiation antigen that is expressed in a high percentage of melanoma cell lines. A similar sequence gene in medaka fish, 'B,' encodes a transporter that mediates melanin synthesis. Mutations in this gene are a cause of oculocutaneous albinism type 4. Alternative splicing results in multiple transcript variants encoding different isoforms. Protein expression is localized to the melanosome, and analysis of the by knockdown of RNA expression leads to altered melanosome pH potentially altering tyrosinase function by affecting copper binding.

In melanocytic cell types, the SLC45A2 gene is regulated by microphthalmia-associated transcription factor.

SLC45A2 has been found to play a role in pigmentation in several species. In humans, it has been identified as a factor in the light skin of Europeans and as an ancestry-informative marker for distinguishing Sri Lankan from European ancestry. Mutations in the gene have also been identified as the cause of human Type IV oculocutaneous albinism. SLC45A2 is the so-called cream gene responsible in horses for buckskin, palomino and cremello coloration, while a mutation in this gene underlies the white tiger variant. In dogs a mutation to this gene causes white fur, pink skin, and blue eyes.

SLC45A2 was identified as a melanoma tumor-associated antigen with high tumor specificity and reduced potential for autoimmune toxicity, and is currently in clinical development as a target for T-cell based immunotherapy.

References

References

1. (Mar 2002). "Distinctive distribution of AIM1 polymorphism among major human populations with different skin color". Journal of Human Genetics.
2. (November 2001). "Mutations in the human orthologue of the mouse underwhite gene (uw) underlie a new form of oculocutaneous albinism, OCA4". American Journal of Human Genetics.
3. "Entrez Gene: SLC45A2 solute carrier family 45, member 2".
4. (2003). "A mutation in the MATP gene causes the cream coat colour in the horse". Genetics, Selection, Evolution.
5. (February 2001). "Use of an in vitro immunoselected tumor line to identify shared melanoma antigens recognized by HLA-A*0201-restricted T cells". Cancer Research.
6. (2015). "Membrane-Associated Transporter Protein (MATP) Regulates Melanosomal pH and Influences Tyrosinase Activity". PLOS ONE.
7. (January 2002). "Identification of Aim-1 as the underwhite mouse mutant and its transcriptional regulation by MITF". The Journal of Biological Chemistry.
8. (December 2008). "Novel MITF targets identified using a two-step DNA microarray strategy". Pigment Cell & Melanoma Research.
9. (January 2007). "Population differences of two coding SNPs in pigmentation-related genes SLC24A5 and SLC45A2". International Journal of Legal Medicine.
10. "OMIM Entry - #606574 - ALBINISM, OCULOCUTANEOUS, TYPE IV; OCA4". [[Johns Hopkins University]].
11. (June 2013). "The genetic basis of white tigers". Current Biology.
12. (May–June 2015). "A Missense Mutation in SLC45A2 Is Associated with Albinism in Several Small Long Haired Dog Breeds". The Journal of Heredity.
13. (August 2017). "SLC45A2: A Melanoma Antigen with High Tumor Selectivity and Reduced Potential for Autoimmune Toxicity". Cancer Immunology Research.