PMEL
Available structures PDB Ortholog search: PDBe RCSB List of PDB id codes 1TVB, 1TVH, 3CC5, 4IS6, 5EU6, 5EU4, 5EU3
Identifiers
Aliases	PMEL, D12S53E, ME20, ME20-M, ME20M, P1, P100, PMEL17, SI, SIL, SILV, gp100, premelanosome protein, HMB-45, HMB45
External IDs	OMIM: 155550 MGI: 98301 HomoloGene: 5048 GeneCards: PMEL
Gene location (Human) Chr. Chromosome 12 (human)[1] Band 12q13.2 Start 55,954,105 bp[1] End 55,973,317 bp[1]
Gene location (Mouse) Chr. Chromosome 10 (mouse)[2] Band 10 D3|10 77.13 cM Start 128,540,064 bp[2] End 128,556,107 bp[2]
RNA expression pattern Bgee Human Mouse (ortholog) Top expressed in retinal pigment epithelium vulva skin of abdomen human penis nipple right lobe of liver body of pancreas lymph node canal of the cervix smooth muscle tissue Top expressed in iris hair follicle ciliary body utricle conjunctival fornix spermatid cornea retinal pigment epithelium skin of back spermatocyte More reference expression data BioGPS More reference expression data
Gene ontology Molecular function protein binding identical protein binding Cellular component multivesicular body membrane extracellular region multivesicular body membrane integral component of membrane endosome plasma membrane endoplasmic reticulum melanosome Golgi apparatus endoplasmic reticulum membrane integral component of plasma membrane Biological process melanin biosynthetic process melanosome organization developmental pigmentation Sources:Amigo / QuickGO
Orthologs Species Human Mouse Entrez 6490 20431 Ensembl ENSG00000185664 ENSMUSG00000025359 UniProt P40967 Q60696 Q9CZB2 RefSeq (mRNA) NM_001200053 NM_001200054 NM_006928 NM_001320121 NM_001320122 NM_001384361 NM_021882 RefSeq (protein) NP_001186982 NP_001186983 NP_001307050 NP_001307051 NP_008859 NP_068682 Location (UCSC) Chr 12: 55.95 – 55.97 Mb Chr 10: 128.54 – 128.56 Mb PubMed search [3] [4]
Wikidata
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Melanocyte protein PMEL also known as premelanosome protein (PMEL), silver locus protein homolog (SILV) or Glycoprotein 100 (gp100), is a protein that in humans is encoded by the PMEL gene.^[5][6] Its gene product may be referred to as PMEL, silver, ME20, gp100 or Pmel17.

Structure and function

PMEL is a 100 kDa, 661 amino acids long type I transmembrane glycoprotein that is expressed primarily in melanosomes, which are the melanin-producing organelles in melanocytes of pigment cells of the skin and eye, and in most malignant melanomas.

This protein is involved in melanosome maturation, including melanogenesis, melanosome biogenesis, and melanin polymerization (Eisenberg) [1]. The transmembrane form of PMEL is modified in the secretory pathway by elaboration of N-linked oligosaccharides and addition and modification of O-linked oligosaccharides. It is then targeted to precursors of the pigment organelle, the melanosome, where it is proteolytically processed to several small fragments. Some of these fragments form non-pathological amyloid that assemble into sheets and form the striated pattern that underlies melanosomal ultrastructure. PMEL cleavage is mediated by several proteases including a proprotein convertase of the furin family, a "sheddase" that might include members of the a disintegrin and metalloproteinase (ADAM) family, and additional proteases in melanosomes or their precursors. After the amyloidogenic region is cleaved, the small remaining integral membrane fragment is digested by γ-secretase.

The expression of the PMEL gene is regulated by the microphthalmia-associated transcription factor (MITF).^[7][8]

Function in cancer and cancer treatment

The gp100 protein is a melanoma antigen i.e. a tumor-associated antigen.

Short fragments of it have been used to develop the gp100 cancer vaccine which is or contains gp100:209-217(210M).^[9]

Hydrophilic recombinant gp100 protein (HR-gp100) has been topically applied on human intact skin in vitro, and used as a vaccine in a mouse model. It was demonstrated that HR-gp100 permeates into human skin, and is processed and presented by human dendritic cells. In the mouse model, an HR-gp100-based vaccine triggered antigen-specific T cell responses, as shown by proliferation assays, ELISA and intracellular staining for IFN-γ.

The gp100 protein contains differentiation antigens.[2], and has been widely studied to be used as a target for melanoma immunotherapy. Different sequences of the GP100 peptide could be used for immunization against tumors. According to a case study, modifications of GP100, such as GP100-209 and GP100-208, have shown a greater number of antigen-specific CTL's (cytotoxic T lymphocytes), which can target and kill cancer cells (Eisenberg).[3]