Usuario:Jcfidy/Gen PMEL

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 PMEL gene.​​ 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.

The expression of the PMEL gene is regulated by the microphthalmia-associated transcription factor (MITF).​​

Further reading

• «Structural characterization of SIL, a gene frequently disrupted in T-cell acute lymphoblastic leukemia.». Mol. Cell. Biol. 11 (11): 5462-9. 1991. PMC 361915. PMID 1922059. doi:10.1128/mcb.11.11.5462. 
• «A melanocyte-specific gene, Pmel 17, maps near the silver coat color locus on mouse chromosome 10 and is in a syntenic region on human chromosome 12.». Proc. Natl. Acad. Sci. U.S.A. 88 (20): 9228-32. 1991. Bibcode:1991PNAS...88.9228K. PMC 52687. PMID 1924386. doi:10.1073/pnas.88.20.9228. 
• «Site-specific recombination of the tal-1 gene is a common occurrence in human T cell leukemia.». EMBO J. 9 (10): 3343-51. 1990. PMC 552072. PMID 2209547. doi:10.1002/j.1460-2075.1990.tb07535.x. 
• Guillaume van Niel; Ptissam Bergam; Aurelie Di Cicco (2015). «Apolipoprotein E Regulates Amyloid Formation within Endosomes of Pigment Cells». Cell Reports 13 (1): 43-51. PMID 26387950. doi:10.1016/j.celrep.2015.08.057. 
  • «Molecular characterization of the melanocyte lineage-specific antigen gp100.». J. Biol. Chem. 269 (31): 20126-33. 1994. PMID 7519602. doi:10.1016/S0021-9258(17)32136-1. 
• «Identification of a human melanoma antigen recognized by tumor-infiltrating lymphocytes associated with in vivo tumor rejection.». Proc. Natl. Acad. Sci. U.S.A. 91 (14): 6458-62. 1994. Bibcode:1994PNAS...91.6458K. PMC 44221. PMID 8022805. doi:10.1073/pnas.91.14.6458. 
• «Cloning and expression of the gene for the melanoma-associated ME20 antigen.». DNA Cell Biol. 13 (2): 87-95. 1994. PMID 8179825. doi:10.1089/dna.1994.13.87. 
• «Genomic organization and sequence of D12S53E (Pmel 17), the human homologue of the mouse silver (si) locus.». J. Invest. Dermatol. 106 (1): 24-7. 1996. PMID 8592076. doi:10.1111/1523-1747.ep12326976. 
• «Polymerization of 5,6-dihydroxyindole-2-carboxylic acid to melanin by the pmel 17/silver locus protein.». Eur. J. Biochem. 236 (1): 180-8. 1996. PMID 8617263. doi:10.1111/j.1432-1033.1996.t01-1-00180.x. 
• «Molecular detection of tumor-associated antigens shared by human cutaneous melanomas and gliomas.». Am. J. Pathol. 150 (6): 2143-52. 1997. PMC 1858329. PMID 9176405. 
• «Analysis of Pmel17/gp100 expression in primary human tissue specimens: implications for melanoma immuno- and gene-therapy.». Cancer Immunol. Immunother. 44 (4): 239-47. 1997. PMID 9222283. S2CID 24294029. doi:10.1007/s002620050379. 
• «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. 1998. PMID 9586889. doi:10.1200/JCO.1998.16.5.1760. 
• «Translation of a retained intron in tyrosinase-related protein (TRP) 2 mRNA generates a new cytotoxic T lymphocyte (CTL)-defined and shared human melanoma antigen not expressed in normal cells of the melanocytic lineage.». J. Exp. Med. 188 (6): 1005-16. 1998. PMC 2212536. PMID 9743519. doi:10.1084/jem.188.6.1005. 
• «Detection of melanoma micrometastases in the sentinel lymph node and in nonsentinel nodes by tyrosinase polymerase chain reaction.». J. Invest. Dermatol. 113 (4): 554-9. 1999. PMID 10504440. doi:10.1046/j.1523-1747.1999.00719.x. 
• «Distinct protein sorting and localization to premelanosomes, melanosomes, and lysosomes in pigmented melanocytic cells.». J. Cell Biol. 152 (4): 809-24. 2001. PMC 2195785. PMID 11266471. doi:10.1083/jcb.152.4.809. 
• «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. 2002. PMID 11549113. doi:10.1034/j.1600-0749.2001.140410.x. 
• «Pmel17 initiates premelanosome morphogenesis within multivesicular bodies.». Mol. Biol. Cell 12 (11): 3451-64. 2002. PMC 60267. PMID 11694580. doi:10.1091/mbc.12.11.3451. 
• «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. 2003. PMID 12135425. doi:10.1034/j.1399-0039.2002.590404.x. 
• «Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences.». Proc. Natl. Acad. Sci. U.S.A. 99 (26): 16899-903. 2003. Bibcode:2002PNAS...9916899M. PMC 139241. PMID 12477932. doi:10.1073/pnas.242603899.