Recombinant Human Melanocyte protein PMEL (PMEL), partial

Function

Represents a potent melanoma-specific antigen. Among melanoma non-mutated self-peptides, G9-154 (KTWGQYWQV), G9-209 (ITDQVPFSV) and G9-280 (YLEPGPVTA), appear to act as immunodominant common epitopes that stimulate anti-tumor immune response mediated by HLA-A-restricted cytotoxic T cells

Subcellular Location

Endoplasmic reticulum membrane (Single-pass type I membrane protein); Golgi apparatus, cis-Golgi network membrane (Single-pass type I membrane protein); Endosome, multivesicular body; Melanosome; Extracellular vesicle; Secreted

Tissue Specificity

Normally expressed at low levels in quiescent adult melanocytes but overexpressed by proliferating neonatal melanocytes and during tumor growth. Overexpressed in melanomas. Some expression was found in dysplastic nevi

Subunit

Homodimer; disulfide-linked. Dimerization in the endoplasmic reticulum and early Golgi prevents premature fibril formation. The dimers are resolved to monomers in late- or post-Golgi compartments (PubMed:26694611). Heterooligomer; amyloid-type. Processed amyloidogenic fragments assemble into fibrils that further organize into beta-sheet quaternary amyloid structures (PubMed:28272432, PubMed:30988362). Interacts (via luminal C-terminal fragment) with CD63; this is important for sorting of the luminal fragment in tetraspanin rich microdomains in stage I melanosomes to prevent premature lysosomal degradation (PubMed:21962903). Interacts with APOE; this allows the loading of the luminal fragment on ILVs to induce fibril nucleation (PubMed:26387950). Interacts with MLANA (PubMed:15695812)

• Kwon B.S. et al. 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. (1991)
• Maresh G.A. et al. Cloning and expression of the gene for the melanoma-associated ME20 antigen. — DNA Cell Biol. (1994)
• Adema G.J. et al. Molecular characterization of the melanocyte lineage-specific antigen gp100. — J. Biol. Chem. (1994)
• Kawakami Y. et al. Identification of a human melanoma antigen recognized by tumor-infiltrating lymphocytes associated with in vivo tumor rejection. — Proc. Natl. Acad. Sci. U.S.A. (1994)
• Bailin T. et al. Genomic organization and sequence of D12S53E (Pmel 17), the human homologue of the mouse silver (si) locus. — J. Invest. Dermatol. (1996)
• Kim K.K. et al. Genomic organization and FISH mapping of human Pmel 17, the putative silver locus. — Pigment Cell Res. (1996)
• Vogel A. et al. Sequence of a melanocyte specific secreted glycoprotein. (NOV-)
• Kalnine N. et al. Cloning of human full-length CDSs in BD Creator(TM) system donor vector. (MAY-)