PMEL (gene)
Protein-coding gene in humans
From Wikipedia, the free encyclopedia
Melanocyte protein PMEL also known as premelanosome protein (PMEL), silver locus protein homolog (SILV) or Glycoprotein 100 (gp100), is a protein that in humans is encoded by the PMEL gene.[5][6] Its gene product may be referred to as PMEL, silver, ME20, gp100 or Pmel17.
| PMEL | ||||||||||||||||||||||||||||||||||||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Identifiers | ||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Aliases | PMEL, D12S53E, ME20, ME20-M, ME20M, P1, P100, PMEL17, SI, SIL, SILV, gp100, premelanosome protein, HMB-45, HMB45 | |||||||||||||||||||||||||||||||||||||||||||||||||||||
| External IDs | OMIM: 155550; MGI: 98301; GeneCards: PMEL | |||||||||||||||||||||||||||||||||||||||||||||||||||||
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Wikidata | ||||||||||||||||||||||||||||||||||||||||||||||||||||||
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||
Structure
MEL is a type I transmembrane glycoprotein that is expressed primarily in melanosomes, which are the melanin-producing organelles in melanocytes of pigment cells of the skin and eye, and in most malignant melanomas.[7] It is 661 amino acids long, with a mass of 100 kDa.[7]
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.[7] It is then targeted to precursors of the pigment organelle, the melanosome, where it is proteolytically processed to several small fragments.[7][8]
Some of these fragments form non-pathological amyloid that assemble into sheets and form the striated pattern that underlies melanosomal ultrastructure.[7][9] 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.[8][10][11] After the amyloidogenic region is cleaved, the small remaining integral membrane fragment is digested by γ-secretase.[11][12]
Function
This protein is involved in melanosome maturation, including melanogenesis, melanosome biogenesis, and melanin polymerization.[13][14]
The expression of the PMEL gene is regulated by the microphthalmia-associated transcription factor (MITF).[15][16]
Clinical significance
The gp100 protein is a melanoma antigen, i.e. a tumor-associated antigen.
The gp100 protein contains differentiation antigens[14] and has been widely studied as a target for melanoma immunotherapy. Different sequences of the GP100 peptide could be used for immunization against tumors. According to a case study, modifications of GP100, such as GP100-209 and GP100-208, have shown a greater number of antigen-specific CTL's (cytotoxic T lymphocytes), which can target and kill cancer cells.[13][14]
Short fragments of PMEL have been used to develop the gp100 cancer vaccine which is or contains gp100:209-217(210M).[17]
Hydrophilic recombinant gp100 protein (HR-gp100) has been topically applied on human intact skin in vitro, and used as a vaccine in a mouse model. It was demonstrated that HR-gp100 permeates into human skin, and is processed and presented by human dendritic cells. In the mouse model, an HR-gp100-based vaccine triggered antigen-specific T cell responses, as shown by proliferation assays, ELISA and intracellular staining for IFN-γ.[13]