Biology:Membrane-associated transporter protein

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Short description: Protein


A representation of the 3D structure of the protein myoglobin showing turquoise α-helices.
Generic protein structure example

Membrane-associated transporter protein (MATP), also known as solute carrier family 45 member 2 (SLC45A2) or melanoma antigen AIM1, is a protein that in humans is encoded by the SLC45A2 gene.[1][2][3]

In human, the SLC45A2 gene is located on the short (p) arm of chromosome 5 at position 13.2.

Function

SLC45A2 is a transporter protein that mediates melanin synthesis. It may regulate the pH of the melanosome, affecting tyrosinase activity.[4] SLC45A2 is also a melanocyte differentiation antigen that is expressed in a high percentage of melanoma cell lines.[5] 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.[3] 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.[6]

In melanocytic cell types, the SLC45A2 gene is regulated by microphthalmia-associated transcription factor.[7][8]

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 (AIM) for distinguishing Sri Lankan from European ancestry.[9] Mutations in the gene have also been identified as the cause of human Type IV oculocutaneous albinism.[10] 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.[11] In dogs a mutation to this gene causes white fur, pink skin, and blue eyes.[12]

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.[13]

See also

References

  1. ↑ "Distinctive distribution of AIM1 polymorphism among major human populations with different skin color". Journal of Human Genetics 47 (2): 92–4. Mar 2002. doi:10.1007/s100380200007. PMID 11916009. 
  2. ↑ "Mutations in the human orthologue of the mouse underwhite gene (uw) underlie a new form of oculocutaneous albinism, OCA4". American Journal of Human Genetics 69 (5): 981–8. November 2001. doi:10.1086/324340. PMID 11574907. 
  3. ↑ 3.0 3.1 "Entrez Gene: SLC45A2 solute carrier family 45, member 2". https://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=51151. 
  4. ↑ Mariat, Denis; Taourit, Sead; Guérin, Gérard (2003). "A mutation in the MATP gene causes the cream coat colour in the horse". Genetics Selection Evolution 35 (1): 119–133. doi:10.1186/1297-9686-35-1-119. PMID 12605854. 
  5. ↑ "Use of an in vitro immunoselected tumor line to identify shared melanoma antigens recognized by HLA-A*0201-restricted T cells". Cancer Research 61 (3): 1089–94. February 2001. PMID 11221837. http://cancerres.aacrjournals.org/content/61/3/1089.long. 
  6. ↑ "Membrane-Associated Transporter Protein (MATP) Regulates Melanosomal pH and Influences Tyrosinase Activity". PLOS ONE 10 (6): e0129273. 2015. doi:10.1371/journal.pone.0129273. PMID 26057890. Bibcode: 2015PLoSO..1029273B. 
  7. ↑ "Identification of Aim-1 as the underwhite mouse mutant and its transcriptional regulation by MITF". The Journal of Biological Chemistry 277 (1): 402–6. January 2002. doi:10.1074/jbc.M110229200. PMID 11700328. 
  8. ↑ "Novel MITF targets identified using a two-step DNA microarray strategy". Pigment Cell & Melanoma Research 21 (6): 665–76. December 2008. doi:10.1111/j.1755-148X.2008.00505.x. PMID 19067971. 
  9. ↑ "Population differences of two coding SNPs in pigmentation-related genes SLC24A5 and SLC45A2". International Journal of Legal Medicine 121 (1): 36–9. January 2007. doi:10.1007/s00414-006-0112-z. PMID 16847698. 
  10. ↑ "OMIM Entry - #606574 - ALBINISM, OCULOCUTANEOUS, TYPE IV; OCA4". Johns Hopkins University. https://omim.org/entry/606574. 
  11. ↑ "The genetic basis of white tigers". Current Biology 23 (11): 1031–5. June 2013. doi:10.1016/j.cub.2013.04.054. PMID 23707431. 
  12. ↑ "A Missense Mutation in SLC45A2 Is Associated with Albinism in Several Small Long Haired Dog Breeds". The Journal of Heredity 106 (3): 285–8. May–June 2015. doi:10.1093/jhered/esv008. PMID 25790827. 
  13. ↑ "SLC45A2: A Melanoma Antigen with High Tumor Selectivity and Reduced Potential for Autoimmune Toxicity". Cancer Immunology Research 5 (8): 618–629. August 2017. doi:10.1158/2326-6066.CIR-17-0051. PMID 28630054. 

Further reading

External links

This article incorporates text from the United States National Library of Medicine, which is in the public domain.




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