Pmel17

Pmel17, also known as premelanosome protein or gp100, is a melanocyte-specific transmembrane glycoprotein that contributes to melanosome maturation and pigment production. It is encoded by the PMEL gene and is expressed in melanocytes of the skin, hair follicles, the uveal tract, and in many melanoma cell lines. The protein localizes to premelanosomes, specialized organelles within pigmented cells where melanin is synthesized and stored.

Function and processing: Pmel17 is synthesized as a type I membrane protein that enters the secretory pathway. It is proteolytically cleaved by proprotein convertases to generate luminal and membrane-associated fragments. The lumenal portion forms amyloid fibrils inside premelanosomes, providing a scaffold that guides the polymerization and deposition of melanin. This functional amyloid formation is tightly regulated and occurs within the organelle to ensure proper pigmentation.

Structure and trafficking: The protein has N-terminal luminal domains that are glycosylated and a C-terminal transmembrane region. After synthesis, it traffics through the endosomal–lysosomal system to premelanosomes, where maturation occurs.

Clinical relevance: gp100 (Pmel17) is a well-known melanoma-associated antigen. Its peptides can be presented by MHC molecules and are recognized by cytotoxic T cells, making PMEL a target in melanoma immunotherapy and a basis for diagnostic assays. Antibodies such as HMB-45 that recognize PMEL/gp100 are used in pathology to identify melanocytic lesions.

Notes: Pmel17 contributes to pigmentary variation and is a model example of functional amyloid in normal physiology.