Melanocyte protein PMEL also known as premelanosome protein (PMEL) or silver locus protein homolog (SILV) is a protein that in humans is encoded by the PMELgene.[5][6] Its gene product may be referred to as PMEL, silver, ME20, gp100 or Pmel17.
Structure and function
PMEL is a 100 kDa type I transmembrane glycoprotein that is expressed primarily in pigment cells of the skin and eye. The transmembrane form of PMEL is modified in the secretory pathway by elaboration of N-linked oligosaccharides and addition and modification of O-linked oligosaccharides. It is then targeted to precursors of the pigment organelle, the melanosome, where it is proteolytically processed to several small fragments. Some of these fragments form non-pathological amyloid that assemble into sheets and form the striated pattern that underlies melanosomal ultrastructure. PMEL cleavage is mediated by several proteases including a proprotein convertase of the furin family, a "sheddase" that might include members of the a disintegrin and metalloproteinase (ADAM) family, and additional proteases in melanosomes or their precursors. After the amyloidogenic region is cleaved, the small remaining integral membrane fragment is digested by γ-secretase.
Maresh GA, Marken JS, Neubauer M, et al. (1994). "Cloning and expression of the gene for the melanoma-associated ME20 antigen". DNA Cell Biol. 13 (2): 87–95. doi:10.1089/dna.1994.13.87. PMID8179825.
Wagner SN, Wagner C, Schultewolter T, Goos M (1997). "Analysis of Pmel17/gp100 expression in primary human tissue specimens: implications for melanoma immuno- and gene-therapy". Cancer Immunol. Immunother. 44 (4): 239–47. doi:10.1007/s002620050379. PMID9222283. S2CID24294029.
Curry BJ, Myers K, Hersey P (1998). "Polymerase chain reaction detection of melanoma cells in the circulation: relation to clinical stage, surgical treatment, and recurrence from melanoma". J. Clin. Oncol. 16 (5): 1760–9. doi:10.1200/JCO.1998.16.5.1760. PMID9586889.
Virador V, Matsunaga N, Matsunaga J, et al. (2002). "Production of melanocyte-specific antibodies to human melanosomal proteins: expression patterns in normal human skin and in cutaneous pigmented lesions". Pigment Cell Res. 14 (4): 289–97. doi:10.1034/j.1600-0749.2001.140410.x. PMID11549113.
Sensi M, Pellegatta S, Vegetti C, et al. (2003). "Identification of a novel gp100/pMel17 peptide presented by HLA-A*6801 and recognized on human melanoma by cytolytic T cell clones". Tissue Antigens. 59 (4): 273–9. doi:10.1034/j.1399-0039.2002.590404.x. PMID12135425.
