Affinage

PMEL

Melanocyte protein PMEL · UniProt P40967

Length
661 aa
Mass
70.3 kDa
Annotated
2026-06-10
100 papers in source corpus 28 papers cited in narrative 28 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 7/7 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

PMEL (Pmel17/gp100/SILV) is a pigment cell-specific type I transmembrane glycoprotein that builds the fibrillar amyloid matrix scaffold within melanosome precursors upon which melanin polymerizes during melanosome maturation (PMID:11694580, PMID:15096515, PMID:21949658). PMEL is transcriptionally driven by MITF, which binds conserved consensus sites in the SILV promoter/enhancer and controls its expression in melanocytes and the retinal pigment epithelium (PMID:12819038, PMID:14643677). The protein traverses a single biosynthetic route from ER through Golgi to endosome-derived premelanosomes (PMID:17991747), where sequential proteolysis generates the luminal fragments that assemble into fibrils: proprotein convertase cleavage occurs during secretion to release disulfide-linked subunits (PMID:11694580, PMID:21247888), and BACE2 — not BACE1 — performs the juxtamembrane cleavage that liberates the luminal domain for fibrillogenesis, a step required for normal pigmentation in vivo (PMID:23754390, PMID:26912421). Amyloid assembly is driven by the N-terminal NTR and PKD-like domains, which form the physiological fibril core and dictate sorting to multivesicular fibrillogenic compartments, while the RPT domain provides a pH-sensitive regulatory role, adopting an in-register parallel β-sheet amyloid fold only at the mildly acidic melanosomal pH (PMID:19840945, PMID:21148556, PMID:23452376, PMID:28272432). Correct trafficking depends on an N-terminal/PKD junction and ER export and endocytic di-leucine sorting signals in the cytoplasmic tail, loss of which (as in the silver mutation) depletes PMEL from endocytic compartments and yields aberrant melanosomes (PMID:16760433, PMID:20231267), and on sialylated core 1 O-glycans required for fibril formation and sorting (PMID:17303571). Genetic ablation of Pmel produces spherical rather than oblong melanosomes with reduced eumelanin, while dominant transmembrane-domain mutations cause pathogenic fibril packing that inhibits pigmentation (PMID:21949658, PMID:21949659). PMEL stability and processing additionally require complex formation with MART-1 (PMID:15695812), and non-synonymous PMEL variants causing defective processing are linked to hereditary pigment dispersion syndrome/pigmentary glaucoma (PMID:30561643).

Mechanistic history

Synthesis pass · year-by-year structured walk · 13 steps
  1. 1994 Medium

    Establishing that PMEL is a structural melanosomal matrix component rather than a melanogenic enzyme reframed how melanosome architecture is built.

    Evidence Subcellular fractionation, metabolic labeling, and negative enzymatic assays in B16 melanoma; defined cDNA/splicing relationship and signal/cleavage sites by protein sequencing

    PMID:7519602 PMID:7961886 PMID:8185325 PMID:8617992

    Open questions at the time
    • The DHICA-converting activity reported (idx 21) was contested by later structural findings
    • Did not define which fragments form fibrils
  2. 2001 High

    Showed PMEL is cleaved into disulfide-linked luminal and membrane subunits and is sufficient to nucleate premelanosome morphogenesis within multivesicular bodies, establishing it as the initiator of melanosome ultrastructure.

    Evidence Posttranslational processing, pulse-chase, immuno-EM, and transfection of nonpigmented cells

    PMID:11694580

    Open questions at the time
    • Did not identify the proteases responsible
    • Domain requirements for fibril formation undefined
  3. 2003 High

    Identified MITF as the direct transcriptional regulator of SILV/PMEL in melanocytes and the RPE, placing PMEL within the master melanocyte differentiation program.

    Evidence EMSA, ChIP, reporter assays with MITF modulation in melanoma cells; in situ hybridization in Mitf-mutant mouse embryos

    PMID:12819038 PMID:14643677

    Open questions at the time
    • Did not address post-transcriptional regulation
    • Other co-regulators not examined
  4. 2004 High

    Mapped the biosynthetic route and sequential N- and C-terminal cleavages that convert immature melanosomes into fibrillar mature organelles.

    Evidence Biochemical fractionation, epitope mapping with multiple antibodies, pulse-chase, immunofluorescence

    PMID:15096515

    Open questions at the time
    • Did not assign specific proteases to each cleavage
    • Route detail later refined (idx 6)
  5. 2005 High

    Demonstrated MART-1 is a physical partner required for PMEL expression, stability, trafficking, and processing, identifying a needed co-factor for fibril formation.

    Evidence Co-IP, siRNA knockdown, and rescue/re-expression with multiple cellular readouts

    PMID:15695812

    Open questions at the time
    • Structural basis of the MART-1/PMEL complex unresolved
    • Whether MART-1 directly affects amyloid assembly not separated from trafficking effects
  6. 2006 High

    Defined the cytoplasmic ER-exit and di-leucine endocytic signals and the domain requirements (RPT for fibrils; N-terminus for processing/trafficking) underlying PMEL routing and fibrillogenesis.

    Evidence Site-directed/deletion mutagenesis, chimeras, pulse-chase, IF and EM in silver mouse melanocytes; AP1/AP2 sorting analysis with isoform rescue

    PMID:16492709 PMID:16682408 PMID:16760433

    Open questions at the time
    • Mechanism linking acidic environment to RPT fibrillization not yet established
    • AP1/AP2 sorting study (idx 13) Medium-confidence, single lab
  7. 2007 High

    Resolved that fibrillar PMEL derives exclusively from PC-cleaved, Golgi-processed isoforms and follows a single biosynthetic route, clarifying which products contribute to the matrix.

    Evidence Antibody epitope mapping, IP, pulse-chase, EndoH sensitivity, immuno-EM

    PMID:17991747

    Open questions at the time
    • Did not define the convertase identity or timing within the secretory path
  8. 2009 High

    Reconstituted amyloid formation in vitro and assigned the PKD domain to the physiological fibril core and trafficking, while showing RPT is needed in vivo but cannot fold alone — implying a regulatory timing role; also characterized regulated ectodomain shedding.

    Evidence In vitro amyloid assays with purified recombinant fragments, TEM, MVB sorting assays; pharmacological dissection of shedding

    PMID:19840945 PMID:19884326

    Open questions at the time
    • Physiological function of secreted sPmel17 unclear (idx 14 Medium-confidence)
    • Trigger that licenses RPT folding in vivo not identified
  9. 2010 High

    Established the structural basis of RPT amyloid (in-register parallel β-sheet) and its pH dependence matching melanosomal pH, and showed the NTR/PKD junction integrity is required for ER export, targeting, and fibril formation.

    Evidence In vitro amyloid assays at varying pH, protease digestion, mass-per-length, solid-state NMR; deletion/missense mutants with ER-export and EM readouts

    PMID:20231267 PMID:21148556

    Open questions at the time
    • High-resolution structure of the full melanosomal fibril core (NTR/PKD) not solved
    • How pH-sensing is structurally encoded in RPT not detailed
  10. 2011 High

    Genetic knockout and cross-species mutation analyses defined PMEL loss-of-function (spherical melanosomes, reduced eumelanin) versus dominant-negative TMD mutations that cause pathogenic fibril packing, and assigned PC cleavage to the secretory pathway.

    Evidence Pmel−/− mouse with multi-tissue EM and eumelanin quantification; transfection of DW chicken/Silver horse TMD mutants; secretion-inhibitor and mutagenesis kinetics

    PMID:21247888 PMID:21949658 PMID:21949659

    Open questions at the time
    • Molecular mechanism by which TMD oligomerization corrupts fibril packing not fully resolved
    • Why coat color effects are mild despite eumelanin loss
  11. 2013 High

    Identified BACE2 as the specific juxtamembrane protease releasing the luminal domain for fibrillogenesis in vivo, and established the PKD domain as the determinant of fibrillogenic-compartment sorting via its unglycosylated state.

    Evidence Bace2−/− vs Bace1−/− mouse coat phenotypes, RNAi, pharmacologic inhibition, overexpression; PMEL/GPNMB PKD domain-swap chimeras

    PMID:23452376 PMID:23754390

    Open questions at the time
    • Whether additional proteases contribute redundantly to luminal release not excluded
    • How N-glycosylation status mechanistically gates PKD sorting unresolved
  12. 2017 High

    Mapped the core amyloid-forming domain residue-by-residue, implicating aromatic π-stacking interactions in melanosomal amyloid nucleation and assembly.

    Evidence Unbiased alanine-scanning mutagenesis with quantitative EM of fibril formation

    PMID:28272432

    Open questions at the time
    • Atomic-resolution model of the CAF fibril not determined
    • Single-lab study
  13. 2019 Medium

    Linked defective PMEL processing/amyloid assembly to hereditary pigment dispersion syndrome and pigmentary glaucoma, extending PMEL function to ocular pigmentation pathology.

    Evidence Exome/targeted sequencing of patient cohorts, variant expression in HeLa with processing and pseudomelanosome morphology, CRISPR pmela zebrafish

    PMID:30561643

    Open questions at the time
    • Causality for individual variants rests on cell-based surrogate assays
    • Mechanism connecting altered fibrils to glaucoma pathophysiology unresolved

Open questions

Synthesis pass · forward-looking unresolved questions
  • A high-resolution structure of the physiological melanosomal fibril and the trigger that times in vivo RPT/PKD amyloid assembly within the melanosome remain undefined.
  • No atomic structure of the full in vivo NTR/PKD/RPT fibril core
  • Mechanism coupling endosomal acidification, glycosylation, and protease cleavage to controlled fibrillization not integrated

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0005198 structural molecule activity 5
Localization
GO:0005768 endosome 3 GO:0005783 endoplasmic reticulum 3 GO:0005886 plasma membrane 3 GO:0005764 lysosome 1
Pathway
R-HSA-392499 Metabolism of proteins 4 R-HSA-1852241 Organelle biogenesis and maintenance 3 R-HSA-9609507 Protein localization 3
Partners
AP1AP2BACE2MITFMLANA

Evidence

Reading pass · 28 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2001 Pmel17 is proteolytically cleaved in a post-Golgi compartment into two disulfide-linked subunits: a large lumenal subunit (M alpha) and an integral membrane subunit (M beta). In transfected nonpigmented cells, Pmel17 associates with intralumenal membrane vesicles of multivesicular bodies, and overexpression drives formation of premelanosomal striation-like structures, indicating Pmel17 is sufficient to initiate premelanosome morphogenesis from within multivesicular bodies. Posttranslational processing analysis, pulse-chase metabolic labeling, immunoelectron microscopy, transfection of nonpigmented cells Molecular biology of the cell High 11694580
2013 BACE2 (not BACE1) cleaves PMEL within its juxtamembrane domain, releasing the luminal domain into endosomal precursors to form functional amyloid fibrils required for melanosome morphogenesis. Bace2−/− but not Bace1−/− mice display coat color defects, confirming BACE2 specificity for PMEL processing in vivo. Bace2−/− and Bace1−/− mouse coat phenotype analysis, RNA silencing, pharmacologic inhibition of BACE2, BACE2 overexpression, biochemical and morphological analyses in human melanocytic cell line Proceedings of the National Academy of Sciences of the United States of America High 23754390
2016 Pharmacological inhibition of BACE2 (and dual BACE1/BACE2 inhibition) impairs PMEL17 proteolytic processing in mouse and human melanocytes, leading to defective melanosome maturation and irreversible hair depigmentation in mice in a dose-dependent manner. In vitro PMEL17 processing assay in mouse and human melanocytes with BACE inhibitor NB-360; bace2+/− and bace2−/− mouse models treated with inhibitor; morphological analysis of retinal pigmented epithelium Scientific reports High 26912421
2006 The internal repeat (RPT) domain of PMEL17 is required for recognition by the HMB-45 antibody and for formation of the fibrillar matrix in melanosomes. Deletion of the RPT domain abolishes fibrillogenesis, while truncation of the C-terminal domain does not significantly affect processing or trafficking, but deletion of the N-terminal domain abrogates both processing and trafficking. Site-directed mutagenesis and deletion mutant analysis, transfection, immunofluorescence, electron microscopy The Journal of biological chemistry High 16682408
2009 Two N-terminal domains of Pmel17 — an N-terminal domain of unknown structure and a polycystic kidney disease-1 (PKD)-like domain — efficiently form amyloid fibrils in vitro using purified recombinant fragments. The PKD domain forms part of the physiological amyloid core in melanocytes and is also required for intracellular trafficking to multivesicular compartments. The RPT domain is required for fibril formation in vivo but is not necessary for fibril formation in vitro and cannot adopt an amyloid fold alone in a physiologically relevant timeframe, implying it plays a regulatory/timing role. In vitro amyloid formation assay with purified recombinant Pmel17 fragments, transmission electron microscopy, immunofluorescence in melanocytes, multivesicular body sorting assays The Journal of biological chemistry High 19840945
2006 The mouse silver mutation truncates the Pmel17 cytoplasmic domain, causing dual trafficking defects: (1) loss of a conserved C-terminal valine ER exit signal that impairs ER export, and (2) loss of a di-leucine-based endocytic signal that causes accumulation at the plasma membrane. These combined defects deplete Pmel17 from endocytic compartments, delay proteolytic maturation required for fibrillogenesis, and result in larger, rounder, more highly pigmented melanosomes with reduced striations. Site-directed mutagenesis, chimeric protein analysis, metabolic pulse-chase, immunofluorescence localization, electron microscopy of silver mouse melanocytes Molecular biology of the cell High 16760433
2007 All fibrillar forms of Pmel17 in melanosomes are derived only from Golgi-processed isoforms that have undergone proprotein convertase (PC) cleavage in endosomes; the transmembrane-linked cleavage products are absent from fibrils. Pmel17 follows a single biosynthetic route from ER through Golgi and endosomes to melanosomes. Antibody epitope mapping, immunoprecipitation, pulse-chase metabolic labeling, endoglycosidase H sensitivity assays, immunoelectron microscopy The Journal of biological chemistry High 17991747
2011 Proprotein convertase (PC) cleavage of Pmel17 occurs during secretion (not in melanosomes) and does not require endocytic entry. Newly synthesized surface Pmel17 is already quantitatively cleaved. Pmel17 function is independent of the specific sequence of its unconventional PC-cleavage motif that lacks arginine at P4. Processing kinetics analysis of wild-type and soluble secreted Pmel17 derivatives, monensin secretion inhibition, site-directed mutagenesis of cleavage motif, pulse-chase metabolic labeling The Journal of biological chemistry High 21247888
2005 MART-1 forms a complex with Pmel17 and is required for Pmel17 expression, stability, trafficking, and the processing required for melanosome structure and maturation. siRNA knockdown of MART-1 impairs Pmel17 function; re-expression of MART-1 in MART-1-negative cells restores Pmel17 processing. Co-immunoprecipitation, siRNA knockdown, transfection/rescue experiments, Western blotting, immunofluorescence The Journal of biological chemistry High 15695812
2003 MITF directly regulates transcription of SILV/PMEL17/GP100: conserved MITF consensus DNA sequences in the SILV promoter/enhancer are bound by MITF in vitro (EMSA) and in vivo (chromatin immunoprecipitation), MITF drives SILV reporter activity, and up- or down-regulation of MITF produces corresponding changes in endogenous SILV expression in melanoma cells. EMSA, chromatin immunoprecipitation (ChIP), reporter assays, MITF overexpression/knockdown with endogenous gene expression readout The American journal of pathology High 12819038
2003 Pmel17 expression in the retinal pigmented epithelium (RPE) during murine development is transcriptionally dependent on Microphthalmia-associated transcription factor (Mitf), as demonstrated by absence of Pmel17 expression in Mitf-mutant embryos. In situ hybridization of Pmel17 mRNA in wild-type vs. Mitf-mutant mouse embryos Gene expression patterns Medium 14643677
2004 Epitope mapping and biochemical analyses show that gp100/Pmel17 undergoes rapid processing in the endoplasmic reticulum and cis-Golgi, is delivered directly to immature melanosomes, and is subsequently cleaved at amino and carboxyl termini in sequential steps that reorganize immature melanosomes into fibrillar mature melanosomes competent for melanin synthesis. Biochemical fractionation, immunochemical epitope mapping with multiple antibodies, pulse-chase metabolic labeling, immunofluorescence The Journal of biological chemistry High 15096515
2007 Sialylated core 1 O-glycans on Pmel17 are required for its fibril-forming capacity and influence its sorting. Pmel17 lacking correct sialic acid and galactose additions loses the ability to form fibrils, as demonstrated in glycosylation-deficient mutant cells. The immature iPmel17 isoform differs from mature mPmel17 in sialic acid content on the RPT domain, which determines sorting through the secretory pathway vs. direct melanosomal delivery. Novel antibody (alphaPEP25h) sensitive to O-glycosylation changes, glycosylation-deficient mutant cell lines, endoglycosidase H sensitivity, sialyltransferase activity analysis, pigmentation assay The Journal of biological chemistry High 17303571
2006 Pmel17 is sorted to melanosomes via two routes: directly or indirectly through the plasma membrane, involving adaptor proteins AP1 (mu1A and mu1B isoforms) and AP2 but not AP3 or AP4. The AP1 mu1B isoform, expressed in polarized cells including melanocytes, specifically restores sorting of Pmel17 to the plasma membrane in cells lacking mu1B. Expression of mu1B in melanocytes is regulated by UV radiation and DKK1. Proteomics of early melanosomes, RT-PCR, immunolabeling, tissue in situ hybridization, transfection with AP1 isoforms, colocalization imaging Journal of cell science Medium 16492709
2009 The secreted form of Pmel17 (sPmel17) is released by regulated proteolytic ectodomain shedding at the juxtamembrane/intramembrane region, independently of proprotein convertase cleavage. Shedding is inhibited at low temperature but not by metalloproteinase inhibitors, and is induced by phorbol ester or calmodulin inhibitor treatment. sPmel17 consists of two fragments linked by disulfide bonds. Multidisciplinary approach including metalloproteinase inhibitors, low-temperature inhibition, phorbol ester/calmodulin inhibitor stimulation, antibody domain mapping, biochemical characterization of secreted fragments FASEB journal Medium 19884326
2010 The repeat (RPT) domains of mouse, zebrafish, and a human splice variant of Pmel17 all form amyloid fibrils specifically at mildly acidic pH (~5.0), consistent with melanosomal pH. Protease digestion, mass per unit length, and solid-state NMR indicate that mouse RPT amyloid has an in-register parallel β-sheet architecture with approximately two RPT molecules per layer. In vitro amyloid formation assay at varying pH, protease digestion, mass per unit length measurements, solid-state NMR The Journal of biological chemistry High 21148556
2011 Complete genetic inactivation of Pmel (Pmel−/−) in mice causes melanosomes to be spherical rather than oblong in melanocytes of skin, retinal pigment epithelium, and uveal tissue, with only mild effects on visible coat color but a substantial reduction in eumelanin content. The phenotype resembles the spontaneous silver mutation, indicating that previously described hyperpigmented alleles in vertebrates are dominant-negative mutations rather than simple loss-of-function. Pmel gene knockout mouse, coat color phenotyping, electron microscopy of melanosomes in multiple cell types, eumelanin quantification, primary melanocyte culture PLoS genetics High 21949658
2011 The Dominant white (DW) chicken and Silver horse (HoSi) PMEL mutations alter the transmembrane domain (TMD), causing aberrant TMD oligomerization and/or altered membrane association, resulting in pathogenic fibril packing that inhibits melanin production. A secondary mutation in Smoky chicken prevents PMEL accumulation in fibrillogenic compartments, functioning as a null allele to avert DW-associated pigment loss. Transfection of mutant PMEL constructs in cultured melanocytes, electron microscopy of fibril morphology, pigmentation assays, analysis of secondary suppressor mutations PLoS genetics High 21949659
2013 The PKD (polycystic kidney disease) domain of PMEL is the determinant of its unique localization to multivesicular premelanosomes and its amyloidogenic properties. Domain-swapping experiments show that replacing the PMEL PKD domain with the homologous PKD domain from GPNMB (which is heavily N-glycosylated) abolishes sorting to fibrillogenic compartments, establishing that N-glycosylation of the GPNMB PKD domain nullifies its sorting function. Domain swap chimeric protein constructs, transfection in melanocytes and HeLa cells, immunofluorescence colocalization, fibril formation assay Pigment cell & melanoma research High 23452376
2010 The integrity of the junction between the N-terminal region (NTR) and the PKD-like domain of Pmel17 is critical for ER export, subcellular targeting to melanosomes, and fibril formation. Deletion and missense mutations disrupting this junction abolish all three functions. Series of deletion and missense mutants of Pmel17, transfection, immunofluorescence, endoglycosidase H sensitivity (ER export assay), electron microscopy The Journal of biological chemistry High 20231267
2017 An unbiased alanine-scanning mutagenesis screen of the PMEL core amyloid-forming (CAF) domain identified numerous essential residues; many of these rely on aromaticity for function, implicating π-stacking interactions in melanosomal amyloid assembly. Several mutants are specifically defective in amyloid nucleation. Alanine-scanning mutagenesis covering entire CAF domain, quantitative electron microscopy analysis of fibril formation for full mutant set Scientific reports High 28272432
1994 The silver locus protein (Pmel17) localizes to the limiting membranes of premelanosomes and cytosolic vesicles by immunoperoxidase electron microscopy. Recombinant Pmel17 expressed in insect cells accelerates conversion of DHICA to melanin in vitro, and this activity is inhibited by anti-Pmel17 antibodies, indicating an intrinsic DHICA-converting function. The purified protein lacks known TRP catalytic activities and does not modulate TRP enzymatic activities. Immunoperoxidase electron microscopy, in vitro DHICA conversion assay with recombinant and natural Pmel17, baculovirus expression, antibody inhibition, subcellular fractionation The Journal of investigative dermatology Medium 8617992
1994 Pmel17 is localized to the melanosome fraction of B16 melanoma cells and is absent from coated vesicles that deliver tyrosinase-related proteins. Metabolic labeling shows the carboxyl terminus is rapidly lost in vivo (within hours), indicating rapid processing or degradation. Pmel17 lacks all known melanogenic catalytic activities of tyrosinase-related proteins and does not modulate them, suggesting it is a structural rather than enzymatic melanosomal matrix protein. Subcellular fractionation of B16 F10 melanoma cells, immunoaffinity purification, metabolic labeling, Western blotting, enzymatic activity assays The Journal of biological chemistry Medium 7961886
1994 The gp100-c1 cDNA and Pmel17 cDNA originate from the same single gene via alternative splicing, encoding glycoproteins of 100 kDa and 10 kDa recognized by diagnostic melanoma antibodies NKI-beteb, HMB-50, and HMB-45. cDNA cloning, nucleotide sequence analysis of genomic DNA, transfection and immunoreactivity testing, Northern blotting The Journal of biological chemistry Medium 7519602
1994 The ME20 antigen (PMEL) signal peptide cleavage occurs at Thr-24, yielding the membrane-bound form ME20-M (residues 25–661). Proteolytic processing at Val-467 generates the secreted form ME20-S (residues 25–467). Complex-type oligosaccharides are present on ME20-S whereas high-mannose structures predominate at the same sites in ME20-M, and inhibiting complex oligosaccharide synthesis with deoxymannojirimycin markedly reduces ME20-S production without affecting ME20-M synthesis. Immunoaffinity purification, amino acid sequencing of processing sites, tryptic peptide mapping, high-performance anion-exchange chromatography of oligosaccharides, deoxymannojirimycin treatment Archives of biochemistry and biophysics High 8185325
2012 Substantial amounts of PMEL17 are accessible at the melanoma cell surface and undergo internalization, routing to a LAMP1-enriched lysosome-related organelle. An antibody-drug conjugate (ADC) targeting surface PMEL17 exhibits target-dependent tumor cell killing in vitro and in vivo. New PMEL17 antibodies detecting endogenous protein, cell-surface accessibility assay, internalization/trafficking analysis to LAMP1+ compartment, in vitro and in vivo ADC killing assays The Journal of biological chemistry Medium 22613716
2019 Non-synonymous PMEL variants associated with hereditary pigment dispersion syndrome/pigmentary glaucoma exhibit defective PMEL protein processing and altered amyloid fibril formation when expressed in HeLa cells (pseudomelanosomes show structural changes in 5 of 9 variants). CRISPR-Cas9 deletion of the zebrafish homologue pmela causes profound pigmentation defects and enlarged anterior eye segments, supporting PMEL's role in ocular pigmentation. Whole exome sequencing, targeted PMEL sequencing in patient cohorts, PMEL variant expression in HeLa cells with processing and pseudomelanosome morphology analysis, CRISPR-Cas9 zebrafish model Human molecular genetics Medium 30561643
2016 Atomic structure of a natural cognate TCR in complex with the gp100(280-288) HLA-A2-restricted epitope reveals relatively high-affinity TCR binding. Alanine scanning across the peptide identifies Glu3 as critically important for TCR binding; Glu3→Ala substitution causes a molecular switch transmitted to adjacent residues that abrogates TCR binding and T-cell recognition. X-ray crystallography of TCR-pMHC complex, alanine scan mutagenesis of gp100 peptide, T-cell functional assays The Journal of biological chemistry High 26917722

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2011 gp100 peptide vaccine and interleukin-2 in patients with advanced melanoma. The New England journal of medicine 669 21631324
1998 gp100/pmel 17 is a murine tumor rejection antigen: induction of "self"-reactive, tumoricidal T cells using high-affinity, altered peptide ligand. The Journal of experimental medicine 413 9670040
2001 Pmel17 initiates premelanosome morphogenesis within multivesicular bodies. Molecular biology of the cell 259 11694580
2003 MLANA/MART1 and SILV/PMEL17/GP100 are transcriptionally regulated by MITF in melanocytes and melanoma. The American journal of pathology 233 12819038
2020 Tebentafusp, A TCR/Anti-CD3 Bispecific Fusion Protein Targeting gp100, Potently Activated Antitumor Immune Responses in Patients with Metastatic Melanoma. Clinical cancer research : an official journal of the American Association for Cancer Research 208 32816891
2004 The Dominant white, Dun and Smoky color variants in chicken are associated with insertion/deletion polymorphisms in the PMEL17 gene. Genetics 184 15579702
2005 The Silver locus product Pmel17/gp100/Silv/ME20: controversial in name and in function. Pigment cell research 175 16162173
2004 HER-2, gp100, and MAGE-1 are expressed in human glioblastoma and recognized by cytotoxic T cells. Cancer research 165 15256472
1997 Heterogeneous expression of immunotherapy candidate proteins gp100, MART-1, and tyrosinase in human melanoma cell lines and in human melanocytic lesions. Cancer research 158 9242453
1994 Molecular characterization of the melanocyte lineage-specific antigen gp100. The Journal of biological chemistry 157 7519602
1988 Comparison of HMB-45 monoclonal antibody and S-100 protein in the immunohistochemical diagnosis of melanoma. American journal of clinical pathology 155 2459952
2013 BACE2 processes PMEL to form the melanosome amyloid matrix in pigment cells. Proceedings of the National Academy of Sciences of the United States of America 154 23754390
1991 A melanocyte-specific gene, Pmel 17, maps near the silver coat color locus on mouse chromosome 10 and is in a syntenic region on human chromosome 12. Proceedings of the National Academy of Sciences of the United States of America 148 1924386
2005 MART-1 is required for the function of the melanosomal matrix protein PMEL17/GP100 and the maturation of melanosomes. The Journal of biological chemistry 147 15695812
2013 PMEL: a pigment cell-specific model for functional amyloid formation. Pigment cell & melanoma research 146 23350640
1991 HMB-45 staining in benign and malignant melanocytic lesions. A reflection of cellular activation. The American Journal of dermatopathology 130 1725245
1994 The Pmel 17/silver locus protein. Characterization and investigation of its melanogenic function. The Journal of biological chemistry 128 7961886
1996 Analysis of expression of the melanoma-associated antigens MART-1 and gp100 in metastatic melanoma cell lines and in in situ lesions. Journal of immunotherapy with emphasis on tumor immunology : official journal of the Society for Biological Therapy 126 8811494
2006 Expression of nine tumour antigens in a series of human glioblastoma multiforme: interest of EGFRvIII, IL-13Ralpha2, gp100 and TRP-2 for immunotherapy. Journal of neuro-oncology 122 17004103
1997 Learning impairments following injection of a selective cholinergic immunotoxin, ME20.4 IgG-saporin, into the basal nucleus of Meynert in monkeys. Neuroscience 113 9300425
2001 Analysis of microphthalmia transcription factor expression in normal tissues and tumors, and comparison of its expression with S-100 protein, gp100, and tyrosinase in desmoplastic malignant melanoma. The American journal of surgical pathology 112 11176068
2006 A missense mutation in PMEL17 is associated with the Silver coat color in the horse. BMC genetics 110 17029645
2011 Inactivation of Pmel alters melanosome shape but has only a subtle effect on visible pigmentation. PLoS genetics 107 21949658
1989 HMB-45 recognizes stimulated melanocytes. Journal of cutaneous pathology 103 2668355
2004 Uterine epithelioid leiomyosarcomas with clear cells: reactivity with HMB-45 and the concept of PEComa. The American journal of surgical pathology 101 15043315
2006 The repeat domain of the melanosomal matrix protein PMEL17/GP100 is required for the formation of organellar fibers. The Journal of biological chemistry 97 16682408
2004 Mannose receptor targeting of tumor antigen pmel17 to human dendritic cells directs anti-melanoma T cell responses via multiple HLA molecules. Journal of immunology (Baltimore, Md. : 1950) 96 14978085
1993 Melanocyte lineage-specific antigens recognized by monoclonal antibodies NKI-beteb, HMB-50, and HMB-45 are encoded by a single cDNA. The American journal of pathology 96 7504884
2009 N-terminal domains elicit formation of functional Pmel17 amyloid fibrils. The Journal of biological chemistry 95 19840945
2016 PMEL Amyloid Fibril Formation: The Bright Steps of Pigmentation. International journal of molecular sciences 93 27589732
2005 MAGE-A1-, MAGE-A10-, and gp100-derived peptides are immunogenic when combined with granulocyte-macrophage colony-stimulating factor and montanide ISA-51 adjuvant and administered as part of a multipeptide vaccine for melanoma. Journal of immunology (Baltimore, Md. : 1950) 93 15728523
1997 Cloning and characterization of the genes encoding the murine homologues of the human melanoma antigens MART1 and gp100. Journal of immunotherapy (Hagerstown, Md. : 1997) 93 9101410
1993 Pigmentation genes: the tyrosinase gene family and the pmel 17 gene family. The Journal of investigative dermatology 90 8432998
1993 Renal angiomyolipomas and HMB-45 reactivity. Cancer 88 8490837
2003 Cytotoxic T lymphocyte reactivity to gp100, MelanA/MART-1, and tyrosinase, in HLA-A2-positive vitiligo patients. The Journal of investigative dermatology 85 12925214
2006 Dual loss of ER export and endocytic signals with altered melanosome morphology in the silver mutation of Pmel17. Molecular biology of the cell 84 16760433
2003 Expression of the B-cell proliferation marker MUM1 by melanocytic lesions and comparison with S100, gp100 (HMB45), and MelanA. Modern pathology : an official journal of the United States and Canadian Academy of Pathology, Inc 83 12920225
2000 Immunization with DNA coding for gp100 results in CD4 T-cell independent antitumor immunity. Surgery 80 10923004
1996 Shared epitopes for HLA-A3-restricted melanoma-reactive human CTL include a naturally processed epitope from Pmel-17/gp100. Journal of immunology (Baltimore, Md. : 1950) 80 8943411
2003 Targeted immunotherapy using reconstituted chaperone complexes of heat shock protein 110 and melanoma-associated antigen gp100. Cancer research 78 12750279
2004 HMB-45, S-100, NK1/C3, and MART-1 in metastatic melanoma. Human pathology 70 14991540
1996 Characterization and subcellular localization of human Pmel 17/silver, a 110-kDa (pre)melanosomal membrane protein associated with 5,6,-dihydroxyindole-2-carboxylic acid (DHICA) converting activity. The Journal of investigative dermatology 69 8617992
2003 Pmel17 expression is Mitf-dependent and reveals cranial melanoblast migration during murine development. Gene expression patterns : GEP 67 14643677
1997 Immunobiology of human melanoma antigens MART-1 and gp100 and their use for immuno-gene therapy. International reviews of immunology 67 9131386
2007 Premelanosome amyloid-like fibrils are composed of only golgi-processed forms of Pmel17 that have been proteolytically processed in endosomes. The Journal of biological chemistry 66 17991747
1993 Human herpesvirus-6 glycoprotein H and L homologs are components of the gp100 complex and the gH external domain is the target for neutralizing monoclonal antibodies. Virology 62 7692666
2016 Pharmacological BACE1 and BACE2 inhibition induces hair depigmentation by inhibiting PMEL17 processing in mice. Scientific reports 60 26912421
2010 Wild-type and modified gp100 peptide-pulsed dendritic cell vaccination of advanced melanoma patients can lead to long-term clinical responses independent of the peptide used. Cancer immunology, immunotherapy : CII 60 21069321
1998 Autoantibodies to human melanocyte-specific protein pmel17 in the sera of vitiligo patients: a sensitive and quantitative radioimmunoassay (RIA). Clinical and experimental immunology 57 9844040
2012 Interaction of MC1R and PMEL alleles on solid coat colors in Highland cattle. Animal genetics 54 22524257
2004 Epitope mapping of the melanosomal matrix protein gp100 (PMEL17): rapid processing in the endoplasmic reticulum and glycosylation in the early Golgi compartment. The Journal of biological chemistry 53 15096515
1999 Murine dendritic cells transfected with human GP100 elicit both antigen-specific CD8(+) and CD4(+) T-cell responses and are more effective than DNA vaccines at generating anti-tumor immunity. International journal of cancer 49 10508491
1991 HMB-45 monoclonal antibody recognizes an inducible and reversible melanocyte cytoplasmic protein. Journal of cutaneous pathology 47 1761783
1991 Analysis of HMB-45 immunoreactivity in common and cellular blue nevi. Journal of cutaneous pathology 47 1939785
2011 Proprotein convertases process Pmel17 during secretion. The Journal of biological chemistry 46 21247888
2006 Sorting of Pmel17 to melanosomes through the plasma membrane by AP1 and AP2: evidence for the polarized nature of melanocytes. Journal of cell science 46 16492709
1997 Analysis of Pmel17/gp100 expression in primary human tissue specimens: implications for melanoma immuno- and gene-therapy. Cancer immunology, immunotherapy : CII 46 9222283
1996 HMB-45 reactivity in renal leiomyomas and leiomyosarcomas. Modern pathology : an official journal of the United States and Canadian Academy of Pathology, Inc 46 8782205
1993 Significance, specificity, and ultrastructural localization of HMB-45 antigen in pigmented ocular tumors. Ophthalmology 46 8437829
2018 PD-L1 reverses depigmentation in Pmel-1 vitiligo mice by increasing the abundance of Tregs in the skin. Scientific reports 45 29371688
2011 Mutations in or near the transmembrane domain alter PMEL amyloid formation from functional to pathogenic. PLoS genetics 44 21949659
2010 Repeat domains of melanosome matrix protein Pmel17 orthologs form amyloid fibrils at the acidic melanosomal pH. The Journal of biological chemistry 44 21148556
2001 Effective particle-mediated vaccination against mouse melanoma by coadministration of plasmid DNA encoding Gp100 and granulocyte-macrophage colony-stimulating factor. Clinical cancer research : an official journal of the American Association for Cancer Research 42 11309346
1997 Transcription of the gene encoding melanoma-associated antigen gp100 in tissues and cell lines other than those of the melanocytic lineage. British journal of cancer 41 9413942
2021 Linking Parkinson's Disease and Melanoma: Interplay Between α-Synuclein and Pmel17 Amyloid Formation. Movement disorders : official journal of the Movement Disorder Society 40 34021920
2010 Immunologic response to xenogeneic gp100 DNA in melanoma patients: comparison of particle-mediated epidermal delivery with intramuscular injection. Clinical cancer research : an official journal of the American Association for Cancer Research 40 20647477
2007 Sialylated core 1 O-glycans influence the sorting of Pmel17/gp100 and determine its capacity to form fibrils. The Journal of biological chemistry 40 17303571
2001 gp100/pmel17 and tyrosinase encode multiple epitopes recognized by Th1-type CD4+T cells. British journal of cancer 40 11742496
2019 Non-Synonymous variants in premelanosome protein (PMEL) cause ocular pigment dispersion and pigmentary glaucoma. Human molecular genetics 39 30561643
1998 Expression of MAGE, gp100 and tyrosinase genes in uveal melanoma cell lines. Melanoma research 37 9508371
1991 HMB-45 detection in adenocarcinomas. Archives of pathology & laboratory medicine 37 1718237
2021 Gp-100 as a Novel Therapeutic Target in Uveal Melanoma. Cancers 36 34885078
1994 Differential processing and secretion of the melanoma-associated ME20 antigen. Archives of biochemistry and biophysics 36 8185325
2017 Melanosomal formation of PMEL core amyloid is driven by aromatic residues. Scientific reports 35 28272432
2018 Targeting gp100 and TRP-2 with a DNA vaccine: Incorporating T cell epitopes with a human IgG1 antibody induces potent T cell responses that are associated with favourable clinical outcome in a phase I/II trial. Oncoimmunology 34 29872563
2004 HMB-45 (gp103) and MART-1 expression within giant cells in an atypical fibroxanthoma: a case report. Journal of cutaneous pathology 34 14984584
2003 A novel splice variant of Pmel17 expressed by human melanocytes and melanoma cells lacking some of the internal repeats. The Journal of investigative dermatology 34 14632201
2002 Increase of pro-opiomelanocortin mRNA prior to tyrosinase, tyrosinase-related protein 1, dopachrome tautomerase, Pmel-17/gp100, and P-protein mRNA in human skin after ultraviolet B irradiation. The Journal of investigative dermatology 34 11851878
1996 Expression and ultrastructural localization of HMB-45 antigen. The British journal of dermatology 34 8949433
1991 HMB-45-positive malignant lymphoma. A case report with literature review of aberrant HMB-45 reactivity. Archives of pathology & laboratory medicine 34 1713760
2009 The secreted form of a melanocyte membrane-bound glycoprotein (Pmel17/gp100) is released by ectodomain shedding. FASEB journal : official publication of the Federation of American Societies for Experimental Biology 33 19884326
2018 Why Study Functional Amyloids? Lessons from the Repeat Domain of Pmel17. Journal of molecular biology 32 29886018
2014 Identification of the genomic insertion site of Pmel-1 TCR α and β transgenes by next-generation sequencing. PloS one 31 24827921
1998 Human dendritic cells, pulsed with either melanoma tumor cell lysates or the gp100 peptide(280-288), induce pairs of T-cell cultures with similar phenotype and lytic activity. Cellular immunology 31 9637766
2019 Arming T Cells with a gp100-Specific TCR and a CSPG4-Specific CAR Using Combined DNA- and RNA-Based Receptor Transfer. Cancers 30 31137488
2016 A Molecular Switch Abrogates Glycoprotein 100 (gp100) T-cell Receptor (TCR) Targeting of a Human Melanoma Antigen. The Journal of biological chemistry 30 26917722
2002 Frequency of MART-1/MelanA and gp100/PMel17-specific T cells in tumor metastases and cultured tumor-infiltrating lymphocytes. Journal of immunotherapy (Hagerstown, Md. : 1997) 30 12000867
1999 Novel HLA-Cw8-restricted T cell epitopes derived from tyrosinase-related protein-2 and gp100 melanoma antigens. Journal of immunology (Baltimore, Md. : 1950) 30 9973437
2007 HMB-45 and Melan-A are useful in the differential diagnosis between granular cell tumor and malignant melanoma. The American Journal of dermatopathology 29 17284958
1999 Protective immunization against melanoma by gp100 DNA-HVJ-liposome vaccine. Gene therapy 29 10516727
2019 pH-Dependent fibril maturation of a Pmel17 repeat domain isoform revealed by tryptophan fluorescence. Biochimica et biophysica acta. Proteins and proteomics 27 30716507
1997 HMB-45 and tuberin in hamartomas associated with tuberous sclerosis. Modern pathology : an official journal of the United States and Canadian Academy of Pathology, Inc 26 9310961
2013 The PKD domain distinguishes the trafficking and amyloidogenic properties of the pigment cell protein PMEL and its homologue GPNMB. Pigment cell & melanoma research 25 23452376
2010 Endoplasmic reticulum export, subcellular distribution, and fibril formation by Pmel17 require an intact N-terminal domain junction. The Journal of biological chemistry 25 20231267
1996 Expression of gp100 in melanoma metastases resected before or after treatment with IFN alpha and IL-2. Journal of immunotherapy with emphasis on tumor immunology : official journal of the Society for Biological Therapy 25 8941877
1995 Expression cloning of the cDNA encoding a melanoma-associated Ag recognized by mAb HMB-45. Identification as melanocyte-specific Pmel 17 cDNA. Laboratory investigation; a journal of technical methods and pathology 25 7637323
1994 Cloning and expression of the gene for the melanoma-associated ME20 antigen. DNA and cell biology 25 8179825
2017 Effects of microRNA-136 on melanoma cell proliferation, apoptosis, and epithelial-mesenchymal transition by targetting PMEL through the Wnt signaling pathway. Bioscience reports 24 28724603
2012 The melanosomal protein PMEL17 as a target for antibody drug conjugate therapy in melanoma. The Journal of biological chemistry 24 22613716
1996 pMel17 is recognised by monoclonal antibodies NKI-beteb, HMB-45 and HMB-50 and by anti-melanoma CTL. British journal of cancer 24 8624261

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