Pmel
entrez
20431
canonical
uniprot
Q60696
canonical
ensembl
ENSMUSG00000025359
resolver
ensp
ENSMUSP00000051869
resolver
enst
ENSMUST00000054125
resolver
genesymbol
Pmel
resolver
genesymbol_syn
D10H12S53E
resolver
genesymbol_syn
Pmel17
resolver
genesymbol_syn
Si
resolver
genesymbol_syn
Silv
resolver
uniprot
Q9CZB2
resolver
uniprot_entry
PMEL_MOUSE
resolver
uniprot_sec
Q9CZB2
resolver
amino_acid_sequence
MGVQRRSFLPVLVLSALLAVGALEGSRNQDWLGVPRQLVTKTWNRQLYPEWTEVQGSNCWRGGQVSLRVINDGPTLVGANASFSIALHFPGSQKVLPDGQVIWANNTIINGSQVWGGQPVYPQEPDDACVFPDGGPCPSGPKPPKRSFVYVWKTWGKYWQVLGGPVSRLSIATGHAKLGTHTMEVTVYHRRGSQSYVPLAHASSTFTITDQVPFSVSVSQLQALDGETKHFLRNHPLIFALQLHDPSGYLAEADLSYTWDFGDGTGTLISRALDVTHTYLESGSVTAQVVLQAAIPLVSCGSSPVPGTTDGYMPTAEAPGTTSRQGTTTKVVGTTPGQMPTTQPSGTTVVQMPTTEVTATTSEQMLTSAVIDTTLAEVSTTEGTGTTPTRPSGTTVAQATTTEGPDASPLLPTQSSTGSISPLLDDTDTIMLVKRQVPLDCVLYRYGSFSLALDIVQGIESAEILQAVPFSEGDAFELTVSCQGGLPKEACMDISSPGCQPPAQRLCQSVPPSPDCQLVLHQVLKGGSGTYCLNVSLADANSLAVASTQLVVPGQDGGLGQAPLLVGILLVLVAVVLASLIHRHRLKKQGSVSQMPHGSTHWLRLPPVFRARGLGENSPLLSGQQV
uniprot
proteins
disease_involvement
DISEASE: Note=Defects in Silver mutants are the cause of the silver coat color which seems to be due to premature death of pigment cells during the hair cycle. {ECO:0000305}.
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:0000250|UniProtKB:P40967, ECO:0000269|PubMed:21949658, ECO:0000269|PubMed:30988362}.
uniprot
proteins
mass_dalton
66301
uniprot
proteins
mutagenesis
MUTAGEN 299; /note="S->G: Forms abnormal block-like assemblies devoid of fibrillar sheet structure; when associated with 304-P--T-429 del."; /evidence="ECO:0000269|PubMed:30988362"; MUTAGEN 302; /note="S->P: Forms abnormal block-like assemblies devoid of fibrillar sheet structure; when associated with 304-P--T-429 del."; /evidence="ECO:0000269|PubMed:30988362"; MUTAGEN 303; /note="S->G: Forms abnormal block-like assemblies devoid of fibrillar sheet structure; when associated with 304-P--T-429 del."; /evidence="ECO:0000269|PubMed:30988362"; MUTAGEN 304..429; /note="Missing: Forms abnormal block-like assemblies devoid of fibrillar sheet structure. Does not affect protein maturation. Does not affect fibril formation."; /evidence="ECO:0000269|PubMed:30988362
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:0000250|UniProtKB:P40967, ECO:0000269|PubMed:16760433}.; 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. 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 metalloproteases 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. {ECO:0000250|UniProtKB:P40967, ECO:0000269|PubMed:11694580}.
uniprot
proteins
protein_family
PMEL/NMB family
uniprot
proteins
pubmed
10594241
uniprot
proteins
pubmed
11217851
uniprot
proteins
pubmed
11694580
uniprot
proteins
pubmed
12477932
uniprot
proteins
pubmed
16141072
uniprot
proteins
pubmed
16760433
uniprot
proteins
pubmed
21949658
uniprot
proteins
pubmed
30988362
uniprot
proteins
pubmed
7870580
uniprot
proteins
sequence_length
626
uniprot
proteins
subcellular_location
SUBCELLULAR LOCATION: Endoplasmic reticulum membrane {ECO:0000250|UniProtKB:P40967}; Single-pass type I membrane protein {ECO:0000255}. Golgi apparatus, cis-Golgi network membrane {ECO:0000250|UniProtKB:P40967}; Single-pass type I membrane protein {ECO:0000255}. Endosome, multivesicular body {ECO:0000250|UniProtKB:P40967}. Melanosome {ECO:0000250|UniProtKB:P40967}. Extracellular vesicle {ECO:0000250|UniProtKB:P40967}. Secreted {ECO:0000250|UniProtKB:P40967}. Note=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 at exosomes and in intraluminal vesicles within multivesicular endosomes. {ECO:0000250|UniProtKB:P40967}.
uniprot
proteins
transmembrane_region
TRANSMEM 562..582; /note="Helical"; /evidence="ECO:0000255
uniprot
proteins