Membrane-associated transporter protein

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.^[5][6][7]

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

SLC45A2
Identifiers
Aliases	SLC45A2, 1A1, AIM1, MATP, OCA4, SHEP5, solute carrier family 45 member 2
External IDs	OMIM: 606202; MGI: 2153040; HomoloGene: 9412; GeneCards: SLC45A2; OMA:SLC45A2 - orthologs
Gene location (Human) Chr. Chromosome 5 (human)[1] Band 5p13.2 Start 33,944,623 bp[1] End 33,984,693 bp[1]
Gene location (Mouse) Chr. Chromosome 15 (mouse)[2] Band 15 A1|15 5.4 cM Start 11,000,807 bp[2] End 11,029,319 bp[2]
RNA expression pattern Bgee Human Mouse (ortholog) Top expressed in testicle retinal pigment epithelium gonad right lobe of liver islet of Langerhans right auricle skin of leg hypothalamus human kidney fundus Top expressed in iris stria vascularis hair follicle gastrula ciliary body surface ectoderm embryo primary oocyte cornea cochlea More reference expression data BioGPS More reference expression data
Gene ontology Molecular function sucrose:proton symporter activity Cellular component melanosome membrane integral component of membrane membrane Biological process sucrose transport developmental pigmentation melanin biosynthetic process response to stimulus visual perception Sources:Amigo / QuickGO
Orthologs Species Human Mouse Entrez 51151 22293 Ensembl ENSG00000281919 ENSG00000164175 ENSMUSG00000022243 UniProt Q9UMX9 P58355 RefSeq (mRNA) NM_001012509 NM_001297417 NM_016180 NM_053077 RefSeq (protein) NP_001012527 NP_001284346 NP_057264 NP_444307 Location (UCSC) Chr 5: 33.94 – 33.98 Mb Chr 15: 11 – 11.03 Mb PubMed search [3] [4]
Wikidata
View/Edit Human View/Edit Mouse

Function

SLC45A2 is a transporter protein that mediates melanin synthesis. It may regulate the pH of the melanosome, affecting tyrosinase activity.^[8] SLC45A2 is also a melanocyte differentiation antigen that is expressed in a high percentage of melanoma cell lines.^[9] 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.^[7] 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.^[10]

In melanocytic cell types, the SLC45A2 gene is regulated by microphthalmia-associated transcription factor.^[11][12]

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.^[13] Mutations in the gene have also been identified as the cause of human Type IV oculocutaneous albinism.^[14] 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.^[15] In dogs a mutation to this gene causes white fur, pink skin, and blue eyes.^[16]

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.^[17]

See also

• Solute carrier family

References

1. ENSG00000164175 GRCh38: Ensembl release 89: ENSG00000281919, ENSG00000164175 – Ensembl, May 2017
2. GRCm38: Ensembl release 89: ENSMUSG00000022243 – Ensembl, May 2017
3. "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
4. "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
5. Nakayama K, Fukamachi S, Kimura H, Koda Y, Soemantri A, Ishida T (Mar 2002). "Distinctive distribution of AIM1 polymorphism among major human populations with different skin color". Journal of Human Genetics. 47 (2): 92–4. doi:10.1007/s100380200007. PMID 11916009.
6. Newton JM, Cohen-Barak O, Hagiwara N, Gardner JM, Davisson MT, King RA, et al. (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. 69 (5): 981–8. doi:10.1086/324340. PMC 1274374. PMID 11574907.
7. "Entrez Gene: SLC45A2 solute carrier family 45, member 2".
8. Mariat D, Taourit S, Guérin G (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. PMC 2732686. PMID 12605854.
9. Harada M, Li YF, El-Gamil M, Rosenberg SA, Robbins PF (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. 61 (3): 1089–94. PMID 11221837.
10. Bin BH, Bhin J, Yang SH, Shin M, Nam YJ, Choi DH, et al. (2015). "Membrane-Associated Transporter Protein (MATP) Regulates Melanosomal pH and Influences Tyrosinase Activity". PLOS ONE. 10 (6): e0129273. Bibcode:2015PLoSO..1029273B. doi:10.1371/journal.pone.0129273. PMC 4461305. PMID 26057890.
11. Du J, Fisher DE (January 2002). "Identification of Aim-1 as the underwhite mouse mutant and its transcriptional regulation by MITF". The Journal of Biological Chemistry. 277 (1): 402–6. doi:10.1074/jbc.M110229200. PMID 11700328.
12. Hoek KS, Schlegel NC, Eichhoff OM, Widmer DS, Praetorius C, Einarsson SO, et al. (December 2008). "Novel MITF targets identified using a two-step DNA microarray strategy". Pigment Cell & Melanoma Research. 21 (6): 665–76. doi:10.1111/j.1755-148X.2008.00505.x. PMID 19067971. S2CID 24698373.
13. Soejima M, Koda Y (January 2007). "Population differences of two coding SNPs in pigmentation-related genes SLC24A5 and SLC45A2". International Journal of Legal Medicine. 121 (1): 36–9. doi:10.1007/s00414-006-0112-z. PMID 16847698. S2CID 11192076.
14. "OMIM Entry - #606574 - ALBINISM, OCULOCUTANEOUS, TYPE IV; OCA4". Mendelian Inheritance in Man. Johns Hopkins University. Retrieved 2020-08-05.
15. Xu X, Dong GX, Hu XS, Miao L, Zhang XL, Zhang DL, et al. (June 2013). "The genetic basis of white tigers". Current Biology. 23 (11): 1031–5. Bibcode:2013CBio...23.1031X. doi:10.1016/j.cub.2013.04.054. PMID 23707431.
16. Wijesena HR, Schmutz SM (May–June 2015). "A Missense Mutation in SLC45A2 Is Associated with Albinism in Several Small Long Haired Dog Breeds". The Journal of Heredity. 106 (3): 285–8. doi:10.1093/jhered/esv008. PMID 25790827.
17. Park J, Talukder AH, Lim SA, Kim K, Pan K, Melendez B, et al. (August 2017). "SLC45A2: A Melanoma Antigen with High Tumor Selectivity and Reduced Potential for Autoimmune Toxicity". Cancer Immunology Research. 5 (8): 618–629. doi:10.1158/2326-6066.CIR-17-0051. PMC 6087543. PMID 28630054.

Further reading

• Fukamachi S, Shimada A, Shima A (August 2001). "Mutations in the gene encoding B, a novel transporter protein, reduce melanin content in medaka". Nature Genetics. 28 (4): 381–5. doi:10.1038/ng584. PMID 11479596. S2CID 25285273.
• Rundshagen U, Zühlke C, Opitz S, Schwinger E, Käsmann-Kellner B (February 2004). "Mutations in the MATP gene in five German patients affected by oculocutaneous albinism type 4". Human Mutation. 23 (2): 106–10. doi:10.1002/humu.10311. PMID 14722913. S2CID 40612241.
• Inagaki K, Suzuki T, Shimizu H, Ishii N, Umezawa Y, Tada J, et al. (March 2004). "Oculocutaneous albinism type 4 is one of the most common types of albinism in Japan". American Journal of Human Genetics. 74 (3): 466–71. doi:10.1086/382195. PMC 1182260. PMID 14961451.
• Yuasa I, Umetsu K, Watanabe G, Nakamura H, Endoh M, Irizawa Y (December 2004). "MATP polymorphisms in Germans and Japanese: the L374F mutation as a population marker for Caucasoids". International Journal of Legal Medicine. 118 (6): 364–6. doi:10.1007/s00414-004-0490-z. PMID 15455243. S2CID 35270576.
• Suzuki T, Inagaki K, Fukai K, Obana A, Lee ST, Tomita Y (January 2005). "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. doi:10.1111/j.1365-2133.2005.06403.x. PMID 15656822. S2CID 31736225.
• Graf J, Hodgson R, van Daal A (March 2005). "Single nucleotide polymorphisms in the MATP gene are associated with normal human pigmentation variation". Human Mutation. 25 (3): 278–84. doi:10.1002/humu.20143. PMID 15714523. S2CID 31423377.
• Soejima M, Koda Y (January 2007). "Population differences of two coding SNPs in pigmentation-related genes SLC24A5 and SLC45A2". International Journal of Legal Medicine. 121 (1): 36–9. doi:10.1007/s00414-006-0112-z. PMID 16847698. S2CID 11192076.
• Lezirovitz K, Nicastro FS, Pardono E, Abreu-Silva RS, Batissoco AC, Neustein I, et al. (2006). "Is autosomal recessive deafness associated with oculocutaneous albinism a "coincidence syndrome"?". Journal of Human Genetics. 51 (8): 716–20. doi:10.1007/s10038-006-0003-7. PMID 16868655.
• Chi A, Valencia JC, Hu ZZ, Watabe H, Yamaguchi H, Mangini NJ, et al. (November 2006). "Proteomic and bioinformatic characterization of the biogenesis and function of melanosomes". Journal of Proteome Research. 5 (11): 3135–44. doi:10.1021/pr060363j. PMID 17081065.
• Zühlke C, Criée C, Gemoll T, Schillinger T, Kaesmann-Kellner B (June 2007). "Polymorphisms in the genes for oculocutaneous albinism type 1 and type 4 in the German population". Pigment Cell Research. 20 (3): 225–7. doi:10.1111/j.1600-0749.2007.00377.x. PMID 17516931.
• Sengupta M, Chaki M, Arti N, Ray K (August 2007). "SLC45A2 variations in Indian oculocutaneous albinism patients". Molecular Vision. 13: 1406–11. PMID 17768386.

External links

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

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