Membrane-associated transporter protein explained

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]}

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

• Solute carrier family

Further reading

• Fukamachi S, Shimada A, Shima A . Mutations in the gene encoding B, a novel transporter protein, reduce melanin content in medaka . Nature Genetics . 28 . 4 . 381–5 . August 2001 . 11479596 . 10.1038/ng584 . 25285273 .
• Rundshagen U, Zühlke C, Opitz S, Schwinger E, Käsmann-Kellner B . Mutations in the MATP gene in five German patients affected by oculocutaneous albinism type 4 . Human Mutation . 23 . 2 . 106–10 . February 2004 . 14722913 . 10.1002/humu.10311 . 40612241 . free .
• Inagaki K, Suzuki T, Shimizu H, Ishii N, Umezawa Y, Tada J, Kikuchi N, Takata M, Takamori K, Kishibe M, Tanaka M, Miyamura Y, Ito S, Tomita Y . Oculocutaneous albinism type 4 is one of the most common types of albinism in Japan . American Journal of Human Genetics . 74 . 3 . 466–71 . March 2004 . 14961451 . 1182260 . 10.1086/382195 .
• Yuasa I, Umetsu K, Watanabe G, Nakamura H, Endoh M, Irizawa Y . MATP polymorphisms in Germans and Japanese: the L374F mutation as a population marker for Caucasoids . International Journal of Legal Medicine . 118 . 6 . 364–6 . December 2004 . 15455243 . 10.1007/s00414-004-0490-z . 35270576 .
• Suzuki T, Inagaki K, Fukai K, Obana A, Lee ST, Tomita Y . A Korean case of oculocutaneous albinism type IV caused by a D157N mutation in the MATP gene . The British Journal of Dermatology . 152 . 1 . 174–5 . January 2005 . 15656822 . 10.1111/j.1365-2133.2005.06403.x . 31736225 .
• Graf J, Hodgson R, van Daal A . Single nucleotide polymorphisms in the MATP gene are associated with normal human pigmentation variation . Human Mutation . 25 . 3 . 278–84 . March 2005 . 15714523 . 10.1002/humu.20143 . 31423377 . free .
• Soejima M, Koda Y . Population differences of two coding SNPs in pigmentation-related genes SLC24A5 and SLC45A2 . International Journal of Legal Medicine . 121 . 1 . 36–9 . January 2007 . 16847698 . 10.1007/s00414-006-0112-z . 11192076 .
• Lezirovitz K, Nicastro FS, Pardono E, Abreu-Silva RS, Batissoco AC, Neustein I, Spinelli M, Mingroni-Netto RC . Is autosomal recessive deafness associated with oculocutaneous albinism a "coincidence syndrome"? . Journal of Human Genetics . 51 . 8 . 716–20 . 2006 . 16868655 . 10.1007/s10038-006-0003-7 . free .
• Chi A, Valencia JC, Hu ZZ, Watabe H, Yamaguchi H, Mangini NJ, Huang H, Canfield VA, Cheng KC, Yang F, Abe R, Yamagishi S, Shabanowitz J, Hearing VJ, Wu C, Appella E, Hunt DF . Proteomic and bioinformatic characterization of the biogenesis and function of melanosomes . Journal of Proteome Research . 5 . 11 . 3135–44 . November 2006 . 17081065 . 10.1021/pr060363j .
• Zühlke C, Criée C, Gemoll T, Schillinger T, Kaesmann-Kellner B . Polymorphisms in the genes for oculocutaneous albinism type 1 and type 4 in the German population . Pigment Cell Research . 20 . 3 . 225–7 . June 2007 . 17516931 . 10.1111/j.1600-0749.2007.00377.x .
• Sengupta M, Chaki M, Arti N, Ray K . SLC45A2 variations in Indian oculocutaneous albinism patients . Molecular Vision . 13 . 1406–11 . August 2007 . 17768386 .

External links

• GeneReviews/NCBI/NIH/UW entry on Oculocutaneous Albinism Type 4

Notes and References

1. Nakayama K, Fukamachi S, Kimura H, Koda Y, Soemantri A, Ishida T . Distinctive distribution of AIM1 polymorphism among major human populations with different skin color . Journal of Human Genetics . 47 . 2 . 92–4 . Mar 2002 . 11916009 . 10.1007/s100380200007 . free .
2. Newton JM, Cohen-Barak O, Hagiwara N, Gardner JM, Davisson MT, King RA, Brilliant MH . 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 . 11574907 . 1274374 . 10.1086/324340 .
3. Web site: Entrez Gene: SLC45A2 solute carrier family 45, member 2.
4. 10.1186/1297-9686-35-1-119. free. A mutation in the MATP gene causes the cream coat colour in the horse. 2003. Mariat. Denis. Taourit. Sead. Guérin. Gérard. Genetics Selection Evolution. 35. 1. 119–133. 12605854. 2732686.
5. Harada M, Li YF, El-Gamil M, Rosenberg SA, Robbins PF . 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 . 11221837 .
6. Bin BH, Bhin J, Yang SH, Shin M, Nam YJ, Choi DH, Shin DW, Lee AY, Hwang D, Cho EG, Lee TR . Membrane-Associated Transporter Protein (MATP) Regulates Melanosomal pH and Influences Tyrosinase Activity . PLOS ONE . 10 . 6 . e0129273 . 2015 . 26057890 . 4461305 . 10.1371/journal.pone.0129273 . 2015PLoSO..1029273B . free .
7. Du J, Fisher DE . 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 . 11700328 . 10.1074/jbc.M110229200 . free .
8. Hoek KS, Schlegel NC, Eichhoff OM, Widmer DS, Praetorius C, Einarsson SO, Valgeirsdottir S, Bergsteinsdottir K, Schepsky A, Dummer R, Steingrimsson E . Novel MITF targets identified using a two-step DNA microarray strategy . Pigment Cell & Melanoma Research . 21 . 6 . 665–76 . December 2008 . 19067971 . 10.1111/j.1755-148X.2008.00505.x . 24698373 . free .
9. Soejima M, Koda Y . Population differences of two coding SNPs in pigmentation-related genes SLC24A5 and SLC45A2 . International Journal of Legal Medicine . 121 . 1 . 36–9 . January 2007 . 16847698 . 10.1007/s00414-006-0112-z . 11192076 .
10. Web site: OMIM Entry - #606574 - ALBINISM, OCULOCUTANEOUS, TYPE IV; OCA4. 2020-08-05. Mendelian Inheritance in Man. Johns Hopkins University.
11. Xu X, Dong GX, Hu XS, Miao L, Zhang XL, Zhang DL, Yang HD, Zhang TY, Zou ZT, Zhang TT, Zhuang Y, Bhak J, Cho YS, Dai WT, Jiang TJ, Xie C, Li R, Luo SJ . The genetic basis of white tigers . Current Biology . 23 . 11 . 1031–5 . June 2013 . 23707431 . 10.1016/j.cub.2013.04.054 . free . 2013CBio...23.1031X .
12. Wijesena HR, Schmutz SM . 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 . 25790827 . 10.1093/jhered/esv008 . free .
13. Park J, Talukder AH, Lim SA, Kim K, Pan K, Melendez B, Bradley SD, Jackson KR, Khalili JS, Wang J, Creasy C, Pan BF, Woodman SE, Bernatchez C, Hawke D, Hwu P, Lee KM, Roszik J, Lizée G, Yee C . SLC45A2: A Melanoma Antigen with High Tumor Selectivity and Reduced Potential for Autoimmune Toxicity . Cancer Immunology Research . 5 . 8 . 618–629 . August 2017 . 28630054 . 6087543 . 10.1158/2326-6066.CIR-17-0051 .