Protein: Melanocyte protein PMEL (ME20-M) (ME20M) (Melanocyte protein Pmel 17) (Melanocytes lineage-specific antigen GP100) (Melanoma-associated ME20 antigen) (P1) (P100) (Premelanosome protein) (Silver locus protein homolog) [Cleaved into: M-alpha (95 kDa melanocyte-specific secreted glycoprotein) (P26) (Secreted melanoma-associated ME20 antigen) (ME20-S) (ME20S); M-beta] (P40967)
Organism: Homo sapiens (Human)
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.
Subcellular location: Endoplasmic reticulum membrane {ECO:0000269|PubMed:15096515, ECO:0000269|PubMed:15695812, ECO:0000269|PubMed:19047044}; Single-pass type I membrane protein {ECO:0000255}. Golgi apparatus, cis-Golgi network membrane {ECO:0000269|PubMed:15096515}; Single-pass type I membrane protein {ECO:0000255}. Endosome, multivesicular body {ECO:0000269|PubMed:11694580, ECO:0000269|PubMed:17991747, ECO:0000269|PubMed:19047044, ECO:0000269|PubMed:21962903, ECO:0000269|PubMed:26387950}. Melanosome {ECO:0000269|PubMed:11694580, ECO:0000269|PubMed:12643545, ECO:0000269|PubMed:15096515, ECO:0000269|PubMed:15695812, ECO:0000269|PubMed:17081065, ECO:0000269|PubMed:17991747, ECO:0000269|PubMed:23754390}. Extracellular vesicle {ECO:0000269|PubMed:26387950}. Secreted {ECO:0000269|PubMed:8179825}. Note=Identified by mass spectrometry in melanosome fractions from stage I to stage IV (PubMed:17081065). 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 (PubMed:11694580, PubMed:12643545). Sorted to stage I melanosomes following its processing in the ER and cis-Golgi (PubMed:15096515). Transiently expressed at the cell surface before targeting to early melanosomes (PubMed:16760433, PubMed:30988362). Colocalizes with BACE2 in stage I and II melanosomes (PubMed:23754390). Colocalizes with CD63 and APOE at exosomes and in intraluminal vesicles within multivesicular endosomes (PubMed:21962903, PubMed:26387950). {ECO:0000269|PubMed:11694580, ECO:0000269|PubMed:12643545, ECO:0000269|PubMed:15096515, ECO:0000269|PubMed:16760433, ECO:0000269|PubMed:17081065, ECO:0000269|PubMed:21962903, ECO:0000269|PubMed:23754390, ECO:0000269|PubMed:26387950, ECO:0000269|PubMed:30988362}.
Interaction partners:
- Melanoma antigen recognized by T-cells 1
- Tyrosinase
- 5,6-dihydroxyindole-2-carboxylic acid oxidase
- L-dopachrome tautomerase
- T-cell surface glycoprotein CD8 alpha chain
- HLA class I histocompatibility antigen, A alpha chain
- Melanoma-associated antigen 3
- Cancer/testis antigen 1
- CD63 antigen
- G-protein coupled receptor 143
Sequence:
MDLVLKRCLLHLAVIGALLAVGATKVPRNQDWLGVSRQLRTKAWNRQLYPEWTEAQRLDCWRGGQVSLKVSNDGPTLIGANASFSIALNFPGSQKVLPDGQVIWVNNTIINGSQVWGGQPVYPQETDDACIFPDGGPCPSGSWSQKRSFVYVWKTWGQYWQVLGGPVSGLSIGTGRAMLGTHTMEVTVYHRRGSRSYVPLAHSSSAFTITDQVPFSVSVSQLRALDGGNKHFLRNQPLTFALQLHDPSGYLAEADLSYTWDFGDSSGTLISRALVVTHTYLEPGPVTAQVVLQAAIPLTSCGSSPVPGTTDGHRPTAEAPNTTAGQVPTTEVVGTTPGQAPTAEPSGTTSVQVPTTEVISTAPVQMPTAESTGMTPEKVPVSEVMGTTLAEMSTPEATGMTPAEVSIVVLSGTTAAQVTTTEWVETTARELPIPEPEGPDASSIMSTESITGSLGPLLDGTATLRLVKRQVPLDCVLYRYGSFSVTLDIVQGIESAEILQAVPSGEGDAFELTVSCQGGLPKEACMEISSPGCQPPAQRLCQPVLPSPACQLVLHQILKGGSGTYCLNVSLADTNSLAVVSTQLIMPGQEAGLGQVPLIVGILLVLMAVVLASLIYRRRLMKQDFSVPQLPHSSSHWLRLPRIFCSCPIGENSPLLSGQQV