Forms physiological amyloids that play a central role in melanosome morphogenesis and pigmentation. The maturation of unpigmented premelanosomes from stage I to II is marked by assembly of processed amyloidogenic fragments into parallel fibrillar sheets, which elongate the vesicle into a striated ellipsoidal shape. In pigmented stage III and IV melanosomes, the amyloid matrix serves as a platform where eumelanin precursors accumulate at high local concentrations for pigment formation. May prevent pigmentation-associated toxicity by sequestering toxic reaction intermediates of eumelanin biosynthesis pathway.
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 locations: Endoplasmic reticulum membrane, Golgi apparatus, Cis-Golgi network membrane, Endosome, Multivesicular body, Melanosome, Extracellular vesicle, Secreted
Identified by mass spectrometry in melanosome fractions from stage I to stage IV . Localizes predominantly to intralumenal vesicles (ILVs) within multivesicular bodies. Associates with ILVs found within the lumen of premelanosomes and melanosomes and particularly in compartments that serve as precursors to the striated stage II premelanosomes (, ). Sorted to stage I melanosomes following its processing in the ER and cis-Golgi . Transiently expressed at the cell surface before targeting to early melanosomes (, ). Colocalizes with BACE2 in stage I and II melanosomes . Colocalizes with CD63 and APOE at exosomes and in intraluminal vesicles within multivesicular endosomes (, ).
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.