| Post Translational Modifications | N- and O-glycosylated. A small amount of P1/P100 (major form) undergoes glycosylation in ER and Golgi compartments to yield P2/P120 (minor form). The mature P2 form leaves the trans-Golgi network and is mainly targeted to stage I melanosomes via the plasma membrane and clathrin-mediated endocytosis. Stage II melanosomes harbor only Golgi-modified fragments that are derived from M-alpha and that bear sialylated O-linked oligosaccharides. O-glycosylation of the RPT region is a conserved feature likely involved in amyloid sheet separation via electrostatic repulsion. Undergoes multiple proteolytic processing. In a post-Golgi prelysosomal compartment, P2 is cleaved by a furin-like proprotein convertase (PC) into two disulfide-linked subunits: a large lumenal subunit, M-alpha/ME20-S, and an integral membrane subunit, M-beta. Despite cleavage, only a small fraction of M-alpha is secreted, as most M-alpha and M-beta remain associated with each other intracellularly via a disulfide bond. Once targeted to stage I melanosomes, beta-secretase BACE2 cleaves the M-beta fragment to release the amyloidogenic luminal fragment containing M-alpha and a small portion of M-beta N-terminus. M-alpha is further cleaved by metalloproteinases, likely ADAM10 or ADAM17, and still unknown proteases to yield subfragments that ultimately assemble into amyloid fibrils. The C-terminal fragment of M-beta is processed by the gamma-secretase complex to release a short intracytoplasmic domain. |
| Function | 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. |
| Protein Name | Melanocyte Protein PmelMe20-MMe20mMelanocyte Protein Pmel 17Melanocytes Lineage-Specific Antigen Gp100Melanoma-Associated Me20 AntigenP1P100Premelanosome ProteinSilver Locus Protein Homolog Cleaved Into - M-Alpha95 Kda Melanocyte-Specific Secreted GlycoproteinP26Secreted Melanoma-Associated Me20 AntigenMe20-SMe20s - M-Beta |
| Database Links | Reactome: R-HSA-9824585 |
| Cellular Localisation | Endoplasmic Reticulum MembraneSingle-Pass Type I Membrane ProteinGolgi ApparatusCis-Golgi Network MembraneEndosomeMultivesicular BodyMelanosomeExtracellular VesicleSecretedIdentified By Mass Spectrometry In Melanosome Fractions From Stage I To Stage IvLocalizes Predominantly To Intralumenal Vesicles (Ilvs) Within Multivesicular BodiesAssociates With Ilvs Found Within The Lumen Of Premelanosomes And Melanosomes And Particularly In Compartments That Serve As Precursors To The Striated Stage Ii PremelanosomesSorted To Stage I Melanosomes Following Its Processing In The Er And Cis-GolgiTransiently Expressed At The Cell Surface Before Targeting To Early MelanosomesColocalizes With Bace2 In Stage I And Ii MelanosomesColocalizes With Cd63 And Apoe At Exosomes And In Intraluminal Vesicles Within Multivesicular Endosomes |
| Alternative Protein Names | Melanocyte Protein Pmel proteinMe20-M proteinMe20m proteinMelanocyte Protein Pmel 17 proteinMelanocytes Lineage-Specific Antigen Gp100 proteinMelanoma-Associated Me20 Antigen proteinP1 proteinP100 proteinPremelanosome Protein proteinSilver Locus Protein Homolog Cleaved Into - M-Alpha protein95 Kda Melanocyte-Specific Secreted GlycoproteinP26 proteinSecreted Melanoma-Associated Me20 Antigen proteinMe20-S proteinMe20s - M-Beta proteinPMEL proteinD12S53E proteinPMEL17 proteinSILV protein |
Information sourced from Uniprot.org
