PMEL
entrez
6490
canonical
uniprot
P40967
canonical
ensembl
ENSG00000185664
resolver
ensp
ENSP00000402758
resolver
ensp
ENSP00000447374
resolver
ensp
ENSP00000448828
resolver
ensp
ENSP00000450036
resolver
genesymbol
PMEL
resolver
genesymbol_syn
D12S53E
resolver
genesymbol_syn
PMEL17
resolver
genesymbol_syn
SILV
resolver
hgnc
HGNC:10880
resolver
uniprot
B3KS57
resolver
uniprot
B7Z6D7
resolver
uniprot
Q12763
resolver
uniprot
Q14448
resolver
uniprot
Q14817
resolver
uniprot
Q16565
resolver
uniprot_entry
PMEL_HUMAN
resolver
uniprot_sec
B3KS57
resolver
uniprot_sec
B7Z6D7
resolver
uniprot_sec
Q12763
resolver
uniprot_sec
Q14448
resolver
uniprot_sec
Q14817
resolver
uniprot_sec
Q16565
resolver
amino_acid_sequence
MDLVLKRCLLHLAVIGALLAVGATKVPRNQDWLGVSRQLRTKAWNRQLYPEWTEAQRLDCWRGGQVSLKVSNDGPTLIGANASFSIALNFPGSQKVLPDGQVIWVNNTIINGSQVWGGQPVYPQETDDACIFPDGGPCPSGSWSQKRSFVYVWKTWGQYWQVLGGPVSGLSIGTGRAMLGTHTMEVTVYHRRGSRSYVPLAHSSSAFTITDQVPFSVSVSQLRALDGGNKHFLRNQPLTFALQLHDPSGYLAEADLSYTWDFGDSSGTLISRALVVTHTYLEPGPVTAQVVLQAAIPLTSCGSSPVPGTTDGHRPTAEAPNTTAGQVPTTEVVGTTPGQAPTAEPSGTTSVQVPTTEVISTAPVQMPTAESTGMTPEKVPVSEVMGTTLAEMSTPEATGMTPAEVSIVVLSGTTAAQVTTTEWVETTARELPIPEPEGPDASSIMSTESITGSLGPLLDGTATLRLVKRQVPLDCVLYRYGSFSVTLDIVQGIESAEILQAVPSGEGDAFELTVSCQGGLPKEACMEISSPGCQPPAQRLCQPVLPSPACQLVLHQILKGGSGTYCLNVSLADTNSLAVVSTQLIMPGQEAGLGQVPLIVGILLVLMAVVLASLIYRRRLMKQDFSVPQLPHSSSHWLRLPRIFCSCPIGENSPLLSGQQV
uniprot
proteins
function
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. {ECO:0000269|PubMed:11694580, ECO:0000269|PubMed:21962903, ECO:0000269|PubMed:26387950, ECO:0000269|PubMed:26694611, ECO:0000269|PubMed:28272432, ECO:0000269|PubMed:30988362}.; 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. {ECO:0000269|PubMed:7706734, ECO:0000269|PubMed:8022805}.
uniprot
proteins
mass_dalton
70255
uniprot
proteins
mutagenesis
MUTAGEN 60; /note="C->S: Does not affect dimer formation."; /evidence="ECO:0000269|PubMed:26694611"; MUTAGEN 130; /note="C->S: Does not affect dimer formation."; /evidence="ECO:0000269|PubMed:26694611"; MUTAGEN 138; /note="C->S: Does not affect dimer formation."; /evidence="ECO:0000269|PubMed:26694611"; MUTAGEN 149; /note="F->A: Loss-of-function. Retained in the endoplasmic reticulum likely due to misfolding."; /evidence="ECO:0000269|PubMed:28272432"; MUTAGEN 149; /note="F->L: Reduces fibril formation."; /evidence="ECO:0000269|PubMed:28272432"; MUTAGEN 151; /note="Y->A,L: Loss-of-function. Abolishes fibril formation. Does not exert dominant negative effect; when associated with A-211."; /evidence="ECO:0000269|PubMed:28272432"; MUTAGEN 151; /note="Y->F: Has normal fibril formation."; /evidence="ECO:0000269|PubMed:28272432"; MUTAGEN 152; /note="V->A: Markedly reduces fibril formation."; /evidence="ECO:0000269|PubMed:28272432"; MUTAGEN 153; /note="W->A,F: Loss-of-function. Abolishes fibrillar amyloid formation. Does not exert dominant negative effect and retains the amyloidogenic potential; when associated with A-211."; /evidence="ECO:0000269|PubMed:28272432"; MUTAGEN 154; /note="K->A: Reduces fibril formation."; /evidence="ECO:0000269|PubMed:28272432"; MUTAGEN 155; /note="T->A: Reduces fibril formation."; /evidence="ECO:0000269|PubMed:28272432"; MUTAGEN 156; /note="W->A: Reduces fibril formation."; /evidence="ECO:0000269|PubMed:28272432"; MUTAGEN 157; /note="G->A: Reduces fibril formation."; /evidence="ECO:0000269|PubMed:28272432"; MUTAGEN 158; /note="Q->A: Reduces fibril formation."; /evidence="ECO:0000269|PubMed:28272432"; MUTAGEN 159; /note="Y->A: Reduces fibril formation."; /evidence="ECO:0000269|PubMed:28272432"; MUTAGEN 160; /note="W->A,F: Loss-of-function. Abolishes fibril formation. Does not exert dominant negative effect; when associated with A-211."; /evidence="ECO:0000269|PubMed:28272432"; MUTAGEN 161; /note="Q->A: Reduces fibril formation."; /evidence="ECO:0000269|PubMed:28272432"; MUTAGEN 162; /note="V->A: Reduces fibril formation."; /evidence="ECO:0000269|PubMed:28272432"; MUTAGEN 165; /note="G->A: Reduces fibril formation."; /evidence="ECO:0000269|PubMed:28272432"; MUTAGEN 170; /note="L->A: Loss-of-function. Abolishes fibrillar amyloid formation. Does not exert dominant negative effect and retains the amyloidogenic potential; when associated with A-211."; /evidence="ECO:0000269|PubMed:28272432"; MUTAGEN 172; /note="I->A: Loss-of-function. Likely misfolded and rapidly degraded."; /evidence="ECO:0000269|PubMed:28272432"; MUTAGEN 174; /note="T->A: Markedly reduces fibril formation. Does not exert dominant negative effect; when associated with A-211."; /evidence="ECO:0000269|PubMed:28272432"; MUTAGEN 180; /note="G->A: Reduces fibril formation."; /evidence="ECO:0000269|PubMed:28272432"; MUTAGEN 189; /note="Y->A,L: Loss-of-function. Abolishes fibrillar amyloid formation. Does not exert dominant negative effect and retains the amyloidogenic potential; when associated with A-211."; /evidence="ECO:0000269|PubMed:28272432"; MUTAGEN 189; /note="Y->F: Has normal fibril formation."; /evidence="ECO:0000269|PubMed:28272432"; MUTAGEN 191; /note="R->A: Reduces fibril formation."; /evidence="ECO:0000269|PubMed:28272432"; MUTAGEN 192; /note="R->A: Reduces fibril formation."; /evidence="ECO:0000269|PubMed:28272432"; MUTAGEN 200; /note="L->A: Reduces fibril formation."; /evidence="ECO:0000269|PubMed:28272432"; MUTAGEN 207; /note="F->A: Loss-of-function. Abolishes fibrillar amyloid formation. Does not exert dominant negative effect and retains the amyloidogenic potential; when associated with A-211."; /evidence="ECO:0000269|PubMed:28272432"; MUTAGEN 207; /note="F->L: Has normal fibril formation. Reduces fibril formation; when associated with L-215."; /evidence="ECO:0000269|PubMed:28272432"; MUTAGEN 209; /note="I->A: Loss-of-function. Abolishes fibrillar amyloid formation. Does not exert dominant negative effect and retains the amyloidogenic potential; when associated with A-211."; /evidence="ECO:0000269|PubMed:28272432"; MUTAGEN 210; /note="T->A: Reduces fibril formation."; /evidence="ECO:0000269|PubMed:28272432"; MUTAGEN 211; /note="D->A: Forms fibrils at normal levels."; /evidence="ECO:0000269|PubMed:28272432"; MUTAGEN 213; /note="V->A: Reduces fibril formation."; /evidence="ECO:0000269|PubMed:28272432"; MUTAGEN 214; /note="P->A: Reduces fibril formation."; /evidence="ECO:0000269|PubMed:28272432"; MUTAGEN 215; /note="F->A: Reduces fibril formation."; /evidence="ECO:0000269|PubMed:28272432"; MUTAGEN 215; /note="F->L: Has normal fibril formation. Reduces fibril formation; when associated with L-207."; /evidence="ECO:0000269|PubMed:28272432"; MUTAGEN 301; /note="C->S: Abolishes interchain and intrachain disulfide linkage formation."; /evidence="ECO:0000269|PubMed:26694611"; MUTAGEN 468..469; /note="KR->QQ: Loss of proteolytic cleavage."; /evidence="ECO:0000269|PubMed:12732614"; MUTAGEN 475; /note="C->S: Does not affect dimer formation."; /evidence="ECO:0000269|PubMed:26694611"; MUTAGEN 516; /note="C->S: Abolishes disulfide linkage rearrangement that converts dimer to monomer."; /evidence="ECO:0000269|PubMed:26694611"; MUTAGEN 525; /note="C->S: Abolishes disulfide linkage rearrangement that converts dimer to monomer."; /evidence="ECO:0000269|PubMed:26694611"; MUTAGEN 533; /note="C->S: Abolishes disulfide linkage rearrangement that converts dimer to monomer."; /evidence="ECO:0000269|PubMed:26694611"; MUTAGEN 541; /note="C->S: Abolishes disulfide linkage rearrangement that converts dimer to monomer."; /evidence="ECO:0000269|PubMed:26694611"; MUTAGEN 550; /note="C->S: Abolishes disulfide linkage rearrangement that converts dimer to monomer."; /evidence="ECO:0000269|PubMed:26694611"; MUTAGEN 566; /note="C->S: Abolishes disulfide linkage rearrangement that converts dimer to monomer."; /evidence="ECO:0000269|PubMed:26694611"; MUTAGEN 582..585; /note="TQLI->DDDD: Impairs the cleavage of the C-terminal fragment."; /evidence="ECO:0000269|PubMed:19047044"; MUTAGEN 582..585; /note="Missing: Impairs the cleavage of the C-terminal fragment."; /evidence="ECO:0000269|PubMed:19047044"; MUTAGEN 583..584; /note="QL->DD: Impairs the cleavage of the C-terminal fragment."; /evidence="ECO:0000269|PubMed:19047044"; MUTAGEN 637..661; /note="Missing: Leads to inefficient ER exit, endocytic trafficking and protein maturation."; /evidence="ECO:0000269|PubMed:16760433"; MUTAGEN 655..656; /note="LL->AA: Leads to inefficient endocytic trafficking."; /evidence="ECO:0000269|PubMed:16760433"; MUTAGEN 661; /note="V->D: Leads to inefficient ER exit."; /evidence="ECO:0000269|PubMed:16760433
uniprot
proteins
post_translational_modification
PTM: 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. {ECO:0000269|PubMed:11694580, ECO:0000269|PubMed:15096515, ECO:0000269|PubMed:16760433, ECO:0000269|PubMed:17991747, ECO:0000269|PubMed:28272432, ECO:0000269|PubMed:30988362}.; PTM: 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 (PubMed:11694580, PubMed:12732614, PubMed:15096515, PubMed:15695812, PubMed:17991747). 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 (PubMed:23754390). M-alpha is further cleaved by metalloproteinases, likely ADAM10 or ADAM17, and still unknown proteases to yield subfragments that ultimately assemble into amyloid fibrils (PubMed:19047044). The C-terminal fragment of M-beta is processed by the gamma-secretase complex to release a short intracytoplasmic domain (PubMed:19047044). {ECO:0000269|PubMed:11694580, ECO:0000269|PubMed:12732614, ECO:0000269|PubMed:15096515, ECO:0000269|PubMed:15695812, ECO:0000269|PubMed:17991747, ECO:0000269|PubMed:19047044, ECO:0000269|PubMed:23754390}.
uniprot
proteins
protein_family
PMEL/NMB family
uniprot
proteins
pubmed
11694580
uniprot
proteins
pubmed
12643545
uniprot
proteins
pubmed
12732614
uniprot
proteins
pubmed
14632201
uniprot
proteins
pubmed
14702039
uniprot
proteins
pubmed
15096515
uniprot
proteins
pubmed
15489334
uniprot
proteins
pubmed
15695812
uniprot
proteins
pubmed
16541075
uniprot
proteins
pubmed
16682408
uniprot
proteins
pubmed
16760433
uniprot
proteins
pubmed
17081065
uniprot
proteins
pubmed
17991747
uniprot
proteins
pubmed
19047044
uniprot
proteins
pubmed
1924386
uniprot
proteins
pubmed
21962903
uniprot
proteins
pubmed
23754390
uniprot
proteins
pubmed
26387950
uniprot
proteins
pubmed
26694611
uniprot
proteins
pubmed
28272432
uniprot
proteins
pubmed
30988362
uniprot
proteins
pubmed
7519602
uniprot
proteins
pubmed
7706734
uniprot
proteins
pubmed
8022805
uniprot
proteins
pubmed
8179825
uniprot
proteins
pubmed
8592076
uniprot
proteins
pubmed
8739560
uniprot
proteins
sequence_length
661
uniprot
proteins
subcellular_location
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}.
uniprot
proteins
transmembrane_region
TRANSMEM 596..616; /note="Helical"; /evidence="ECO:0000255
uniprot
proteins