The world's first wiki where authorship really matters (Nature Genetics, 2008). Due credit and reputation for authors. Imagine a global collaborative knowledge base for original thoughts. Search thousands of articles and collaborate with scientists around the globe.

wikigene or wiki gene protein drug chemical gene disease author authorship tracking collaborative publishing evolutionary knowledge reputation system wiki2.0 global collaboration genes proteins drugs chemicals diseases compound
Hoffmann, R. A wiki for the life sciences where authorship matters. Nature Genetics (2008)



Gene Review

PMEL  -  premelanosome protein

Homo sapiens

Synonyms: D12S53E, ME20, ME20-M, ME20M, Melanocyte protein PMEL, ...
Welcome! If you are familiar with the subject of this article, you can contribute to this open access knowledge base by deleting incorrect information, restructuring or completely rewriting any text. Read more.

Disease relevance of SILV

  • Tyrosinase and gp100 are expressed in a higher percentage of melanomas than TRP-1(gp75), and the expression of these three antigens was discordant [1].
  • All three patients positive for Pmel17 antibodies (aged 50-63 years) had had vitiligo of the symmetrical type for > 1 year and all of them also had an associated autoimmune disorder: GD in one and autoimmune hypothyroidism in two [2].
  • In contrast, sera from 20 healthy controls, 10 patients with Hashimoto's thyroiditis and 10 patients with Graves' disease (GD) were all negative for Pmel17 antibodies [2].
  • Angiomyolipomas (AMLs) show a characteristic immunoreactivity with melanocyte differentiation markers such as monoclonal antibody (mAb) HMB45, which detects melanocyte differentiation antigen gp100 and mAb A103 reacting with Melan-A/MART-1 [3].
  • METHODS: Three pigment cell specific (PCS) markers-tyrosinase, Pmel-17, and MART-1-and one cancer testis antigen (CTA)-MAGE-3-were selected for use in a multimarker RT-PCR assay [4].

High impact information on SILV

  • In this study, immunodominant peptides from the gp100 melanoma-associated antigen were identified, and a synthetic peptide, designed to increase binding to HLA-A2 molecules, was used as a cancer vaccine to treat patients with metastatic melanoma [5].
  • CTLp's recognizing MAGE-C2 and gp100 antigens were already present before vaccination, but new clonotypes appeared afterwards [6].
  • We additionally show that melanosome-containing multivesicular bodies degranulate extracellularly and release FasL-bearing microvesicles, that coexpress both gp100 and CD63 and retain their functional activity in triggering Fas-dependent apoptosis of lymphoid cells [7].
  • Current strategies for the immunotherapy of melanoma include augmentation of the immune response to tumor antigens represented by melanosomal proteins such as tyrosinase, gp100, and MART-1 [8].
  • To induce autoreactive T cells, we studied immune responses to gp100/pmel 17, an antigen naturally expressed by both normal melanocytes and melanoma cells [9].

Chemical compound and disease context of SILV

  • Anti-Pmel17 immunoprecipitates from metabolically pulse labeled melanoma cells and melanocytes contain, in addition to full-length Pmel17, a glycoprotein that migrates with a lower relative molecular weight [10].
  • We assessed the incidence of SI in offspring of Framingham Heart Study (FHS) patients following unrecognized myocardial infarction (UMI) and in controls without MI but who were matched for age, sex, hypertension, diabetes, smoking, and total cholesterol at entry into the FHS [11].
  • This study was undertaken to determine whether patients with silent ischemia (SI) (a positive thallium stress test without chest pain) have nonchest-pain symptoms that might serve as "anginal equivalents." Two hundred ninety-four individuals on completing a stress test were requested to score ten symptoms on a questionnaire (0 absent; 3 severe) [12].
  • These results show that administration of liposomes containing dexamethasone attenuated SI-induced pulmonary inflammation and fibrosis in rats, and that this protection is independent of some biochemical and functional parameters of damage [13].
  • At Day 20, the DEX-LIP treatment significantly reduced the SI-induced increase in right lung/total body weight ratio and right lung hydroxyproline content, a biochemical index of fibrosis [13].

Biological context of SILV

  • In this study, we have used biochemical and immunochemical approaches to more critically assess the synthesis, processing, glycosylation, and trafficking of gp100 [14].
  • Polyvalent melanoma cell vaccine treatment enhanced anti-MAA antibody responses; however, only anti-TRP-2 and anti-gp100/pmel17 antibody response was enhanced [15].
  • When we re-examined the products of wild-type and silver-mutant mouse si loci, RT-PCR of wild-type RNA and genomic DNA sequence accounted for gp87 but excluded the occurrence of Pmel17 [16].
  • However, no sequence homology was found between either of the Pmel17 epitopes and the aforementioned proteins [17].
  • We identified three previously unknown peptides processed from melanosomal proteins tyrosinase (presented by HLA-A(*)2601 and -B(*)3801) and gp100 (presented by HLA-B(*)07021) and five neoantigens generated by somatic point mutations in the patient's melanoma [18].

Anatomical context of SILV


Associations of SILV with chemical compounds

  • The internal proline/serine/threonine-rich repeat domain (called the RPT domain) of PMEL17 undergoes variable proteolytic cleavage [21].
  • These mRNAs encode tyrosinase, the most essential enzyme for melanin synthesis, and gp100, a melanosomal matrix glycoprotein recognized by monoclonal antibody HMB-45 [22].
  • While CLOT and CLIM are broad-spectrum antimycotics of the azole-type, SILV is a sulphonamide compound with antibacterial and antimycotic properties used topically in veterinary medicine [23].
  • We performed Minimal Inhibitory Concentration (MIC)-testings of 40 clinical isolates of M. pachydermatis against climbazole (CLIM), clotrimazole (CLOT) and silver-sulphadiazine (SILV) [23].
  • Replacement of either cysteine residue with alpha-amino butyric acid in the gp100 peptide, RLPRIFCSC, enhanced CTL recognition, suggesting that the peptide epitope naturally presented on the tumor cell surface may contain reduced cysteine residues [24].
  • Analysis of Pmel17 processing in glycosylation-deficient mutant cells reveals that Pmel17 lacking the correct addition of sialic acid and galactose loses the ability to form fibrils [25].
  • These results demonstrate that the release of the Pmel17 ectodomain, which is critical for melanin amyloidogenesis, is initiated by S2 cleavage at a juxtamembrane position [26].

Physical interactions of SILV

  • We show that MART-1 forms a complex with Pmel17 and affects its expression, stability, trafficking, and the processing which is required for melanosome structure and maturation [27].
  • The Marek's disease herpesvirus B antigen (MDHV-B) complex was previously immunologically identified and molecularly characterized as a set of three glycoproteins designated gp100, gp60, and gp49 on the basis of apparent molecular weight and immunoprecipitation with both polyclonal and monoclonal antibodies [28].

Regulatory relationships of SILV

  • The full-length promoter, including a consensus binding site for MITF was found to contain sequences that suppressed gp100 expression [29].
  • Retroviral transduction of primary human T lymphocytes with either one of the two sets of TCRalphabeta constructs enabled T lymphocytes to specifically kill and produce TNF-alpha when triggered by native gp100(pos)/HLA-A2(pos) tumor target cells as well as gp100 peptide-loaded HLA-A2(pos) tumor cells [30].
  • PURPOSE: We examined in vivo particle-mediated epidermal delivery (PMED) of cDNAs for gp100 and granulocyte macrophage colony-stimulating factor (GM-CSF) into uninvolved skin of melanoma patients [31].

Other interactions of SILV

  • MART-1 is required for the function of the melanosomal matrix protein PMEL17/GP100 and the maturation of melanosomes [27].
  • Interestingly, gp100 and TRP-2 gene transcripts were detected in patients having recurrent and/or metastatic disease at the time of testing [32].
  • To identify the epitopes recognized by these four gp100-reactive CTL, 169 peptides containing HLA-A2.1 binding motifs were synthesized and screened for their recognition by TIL using cytotoxicity and IFN-gamma release assays [20].
  • Adoptive transfer of the four gp100-reactive CTL, but not the other TIL, resulted in tumor regression when infused into autologous patients along with IL-2 [20].
  • Expression characteristics of four other MAAs-Tyr, Tyrp1, Dct, and gp100/Pmel17-were analyzed by RT-PCR [33].

Analytical, diagnostic and therapeutic context of SILV


  1. Immunophenotyping of melanomas for tyrosinase: implications for vaccine development. Chen, Y.T., Stockert, E., Tsang, S., Coplan, K.A., Old, L.J. Proc. Natl. Acad. Sci. U.S.A. (1995) [Pubmed]
  2. Autoantibodies to human melanocyte-specific protein pmel17 in the sera of vitiligo patients: a sensitive and quantitative radioimmunoassay (RIA). Kemp, E.H., Gawkrodger, D.J., Watson, P.F., Weetman, A.P. Clin. Exp. Immunol. (1998) [Pubmed]
  3. Immunohistochemical and reverse transcription-polymerase chain reaction expression analysis of tyrosinase and microphthalmia-associated transcription factor in angiomyolipomas. Jungbluth, A.A., King, R., Fisher, D.E., Iversen, K., Coplan, K., Kolb, D., Williamson, B., Chen, Y.T., Stockert, E., Old, L.J., Busam, K.J. Appl. Immunohistochem. Mol. Morphol. (2001) [Pubmed]
  4. Accurate molecular detection of melanoma nodal metastases: an assessment of multimarker assay specificity, sensitivity, and detection rate. Davids, V., Kidson, S.H., Hanekom, G.S. MP, Mol. Pathol. (2003) [Pubmed]
  5. Immunologic and therapeutic evaluation of a synthetic peptide vaccine for the treatment of patients with metastatic melanoma. Rosenberg, S.A., Yang, J.C., Schwartzentruber, D.J., Hwu, P., Marincola, F.M., Topalian, S.L., Restifo, N.P., Dudley, M.E., Schwarz, S.L., Spiess, P.J., Wunderlich, J.R., Parkhurst, M.R., Kawakami, Y., Seipp, C.A., Einhorn, J.H., White, D.E. Nat. Med. (1998) [Pubmed]
  6. High frequency of antitumor T cells in the blood of melanoma patients before and after vaccination with tumor antigens. Germeau, C., Ma, W., Schiavetti, F., Lurquin, C., Henry, E., Vigneron, N., Brasseur, F., Lethé, B., De Plaen, E., Velu, T., Boon, T., Coulie, P.G. J. Exp. Med. (2005) [Pubmed]
  7. Induction of lymphocyte apoptosis by tumor cell secretion of FasL-bearing microvesicles. Andreola, G., Rivoltini, L., Castelli, C., Huber, V., Perego, P., Deho, P., Squarcina, P., Accornero, P., Lozupone, F., Lugini, L., Stringaro, A., Molinari, A., Arancia, G., Gentile, M., Parmiani, G., Fais, S. J. Exp. Med. (2002) [Pubmed]
  8. Melanocyte destruction after antigen-specific immunotherapy of melanoma: direct evidence of t cell-mediated vitiligo. Yee, C., Thompson, J.A., Roche, P., Byrd, D.R., Lee, P.P., Piepkorn, M., Kenyon, K., Davis, M.M., Riddell, S.R., Greenberg, P.D. J. Exp. Med. (2000) [Pubmed]
  9. gp100/pmel 17 is a murine tumor rejection antigen: induction of "self"-reactive, tumoricidal T cells using high-affinity, altered peptide ligand. Overwijk, W.W., Tsung, A., Irvine, K.R., Parkhurst, M.R., Goletz, T.J., Tsung, K., Carroll, M.W., Liu, C., Moss, B., Rosenberg, S.A., Restifo, N.P. J. Exp. Med. (1998) [Pubmed]
  10. A novel splice variant of Pmel17 expressed by human melanocytes and melanoma cells lacking some of the internal repeats. Nichols, S.E., Harper, D.C., Berson, J.F., Marks, M.S. J. Invest. Dermatol. (2003) [Pubmed]
  11. Silent myocardial ischemia in asymptomatic survivors of unrecognized myocardial infarction and matched controls. Hands, M.E., Sia, S.T., Shook, T.L., Anderson, K., Stone, P.H., Levy, D., Castelli, W.P., Rutherford, J.D. Am. Heart J. (1988) [Pubmed]
  12. Symptoms of patients with silent ischemia as detected by thallium stress testing. Bandu, I., Friedman, H.S., Raggi, P., Fishman, S., Prasada, S., Sacchi, T., Chandramouly, B. Chest (1994) [Pubmed]
  13. Modulation of silica-induced pulmonary toxicity by dexamethasone-containing liposomes. DiMatteo, M., Reasor, M.J. Toxicol. Appl. Pharmacol. (1997) [Pubmed]
  14. Epitope mapping of the melanosomal matrix protein gp100 (PMEL17): rapid processing in the endoplasmic reticulum and glycosylation in the early Golgi compartment. Yasumoto, K., Watabe, H., Valencia, J.C., Kushimoto, T., Kobayashi, T., Appella, E., Hearing, V.J. J. Biol. Chem. (2004) [Pubmed]
  15. Antibody responses to melanoma/melanocyte autoantigens in melanoma patients. Huang, S.K., Okamoto, T., Morton, D.L., Hoon, D.S. J. Invest. Dermatol. (1998) [Pubmed]
  16. New insights on the structure of the mouse silver locus and on the function of the silver protein. Solano, F., Martínez-Esparza, M., Jiménez-Cervantes, C., Hill, S.P., Lozano, J.A., García-Borrón, J.C. Pigment Cell Res. (2000) [Pubmed]
  17. Molecular mapping of epitopes on melanocyte-specific protein Pmel17 which are recognized by autoantibodies in patients with vitiligo. Kemp, E.H., Waterman, E.A., Gawkrodger, D.J., Watson, P.F., Weetman, A.P. Clin. Exp. Immunol. (2001) [Pubmed]
  18. The response of autologous T cells to a human melanoma is dominated by mutated neoantigens. Lennerz, V., Fatho, M., Gentilini, C., Frye, R.A., Lifke, A., Ferel, D., Wölfel, C., Huber, C., Wölfel, T. Proc. Natl. Acad. Sci. U.S.A. (2005) [Pubmed]
  19. Heterogeneous expression of immunotherapy candidate proteins gp100, MART-1, and tyrosinase in human melanoma cell lines and in human melanocytic lesions. de Vries, T.J., Fourkour, A., Wobbes, T., Verkroost, G., Ruiter, D.J., van Muijen, G.N. Cancer Res. (1997) [Pubmed]
  20. Recognition of multiple epitopes in the human melanoma antigen gp100 by tumor-infiltrating T lymphocytes associated with in vivo tumor regression. Kawakami, Y., Eliyahu, S., Jennings, C., Sakaguchi, K., Kang, X., Southwood, S., Robbins, P.F., Sette, A., Appella, E., Rosenberg, S.A. J. Immunol. (1995) [Pubmed]
  21. The repeat domain of the melanosomal matrix protein PMEL17/GP100 is required for the formation of organellar fibers. Hoashi, T., Muller, J., Vieira, W.D., Rouzaud, F., Kikuchi, K., Tamaki, K., Hearing, V.J. J. Biol. Chem. (2006) [Pubmed]
  22. gp100 mRNA is more sensitive than tyrosinase mRNA for RT-PCR amplification to detect circulating melanoma cells in peripheral blood of melanoma patients. Tsukamoto, K., Ueda, M., Hirata, S., Osada, A., Kitamura, R., Takahashi, T., Ichihashi, M., Shimada, S. J. Dermatol. Sci. (2000) [Pubmed]
  23. In vitro activity of climbazole, clotrimazole and silver-sulphadiazine against isolates of Malassezia pachydermatis. Schmidt, A. Zentralblatt Veterinarmedizin Reihe B (1997) [Pubmed]
  24. Identification of new melanoma epitopes on melanosomal proteins recognized by tumor infiltrating T lymphocytes restricted by HLA-A1, -A2, and -A3 alleles. Kawakami, Y., Robbins, P.F., Wang, X., Tupesis, J.P., Parkhurst, M.R., Kang, X., Sakaguchi, K., Appella, E., Rosenberg, S.A. J. Immunol. (1998) [Pubmed]
  25. Sialylated core 1 O-glycans influence the sorting of Pmel17/gp100 and determine its capacity to form fibrils. Valencia, J.C., Rouzaud, F., Julien, S., Chen, K.G., Passeron, T., Yamaguchi, Y., Abu-Asab, M., Tsokos, M., Costin, G.E., Yamaguchi, H., Jenkins, L.M., Nagashima, K., Appella, E., Hearing, V.J. J. Biol. Chem. (2007) [Pubmed]
  26. Formation of Pmel17 amyloid is regulated by juxtamembrane metalloproteinase cleavage, and the resulting C-terminal fragment is a substrate for gamma-secretase. Kummer, M.P., Maruyama, H., Huelsmann, C., Baches, S., Weggen, S., Koo, E.H. J. Biol. Chem. (2009) [Pubmed]
  27. MART-1 is required for the function of the melanosomal matrix protein PMEL17/GP100 and the maturation of melanosomes. Hoashi, T., Watabe, H., Muller, J., Yamaguchi, Y., Vieira, W.D., Hearing, V.J. J. Biol. Chem. (2005) [Pubmed]
  28. Synthesis and processing of the Marek's disease herpesvirus B antigen glycoprotein complex. Sithole, I., Lee, L.F., Velicer, L.F. J. Virol. (1988) [Pubmed]
  29. Expression of gp100 and CDK2 in melanoma cells is not co-regulated by a shared promoter region. Stennett, L.S., Riker, A.I., Kroll, T.M., ChaMberlin, J., Miki, T., Nickoloff, B.J., Le Poole, I.C. Pigment Cell Res. (2004) [Pubmed]
  30. Peptide fine specificity of anti-glycoprotein 100 CTL is preserved following transfer of engineered TCR alpha beta genes into primary human T lymphocytes. Schaft, N., Willemsen, R.A., de Vries, J., Lankiewicz, B., Essers, B.W., Gratama, J.W., Figdor, C.G., Bolhuis, R.L., Debets, R., Adema, G.J. J. Immunol. (2003) [Pubmed]
  31. A Phase I Study of Immunization Using Particle-Mediated Epidermal Delivery of Genes for gp100 and GM-CSF into Uninvolved Skin of Melanoma Patients. Cassaday, R.D., Sondel, P.M., King, D.M., Macklin, M.D., Gan, J., Warner, T.F., Zuleger, C.L., Bridges, A.J., Schalch, H.G., Kim, K.M., Hank, J.A., Mahvi, D.M., Albertini, M.R. Clin. Cancer Res. (2007) [Pubmed]
  32. RT-PCR detection of tyrosinase, gp100, MART1/Melan-A, and TRP-2 gene transcripts in peripheral blood of melanoma patients. Samija, M., Juretić, A., Solarić, M., Samija, I., Bingulac-Popović, J., Grahovac, B., Stanec, M., Oresić, V. Croat. Med. J. (2001) [Pubmed]
  33. Uveal and cutaneous melanoma: shared expression characteristics of melanoma-associated antigens. van Dinten, L.C., Pul, N., van Nieuwpoort, A.F., Out, C.J., Jager, M.J., van den Elsen, P.J. Invest. Ophthalmol. Vis. Sci. (2005) [Pubmed]
  34. Polymerase chain reaction detection of melanoma cells in the circulation: relation to clinical stage, surgical treatment, and recurrence from melanoma. Curry, B.J., Myers, K., Hersey, P. J. Clin. Oncol. (1998) [Pubmed]
  35. Detection of melanoma micrometastases in the sentinel lymph node and in nonsentinel nodes by tyrosinase polymerase chain reaction. Lukowsky, A., Bellmann, B., Ringk, A., Winter, H., Audring, H., Fenske, S., Sterry, W. J. Invest. Dermatol. (1999) [Pubmed]
  36. Recognition of shared melanoma antigens in association with major HLA-A alleles by tumor infiltrating T lymphocytes from 123 patients with melanoma. Kawakami, Y., Dang, N., Wang, X., Tupesis, J., Robbins, P.F., Wang, R.F., Wunderlich, J.R., Yannelli, J.R., Rosenberg, S.A. J. Immunother. (2000) [Pubmed]
  37. Immunogenicity, including vitiligo, and feasibility of vaccination with autologous GM-CSF-transduced tumor cells in metastatic melanoma patients. Luiten, R.M., Kueter, E.W., Mooi, W., Gallee, M.P., Rankin, E.M., Gerritsen, W.R., Clift, S.M., Nooijen, W.J., Weder, P., van de Kasteele, W.F., Sein, J., van den Berk, P.C., Nieweg, O.E., Berns, A.M., Spits, H., de Gast, G.C. J. Clin. Oncol. (2005) [Pubmed]
  38. Mass-spectrometric evaluation of HLA-A*0201-associated peptides identifies dominant naturally processed forms of CTL epitopes from MART-1 and gp100. Skipper, J.C., Gulden, P.H., Hendrickson, R.C., Harthun, N., Caldwell, J.A., Shabanowitz, J., Engelhard, V.H., Hunt, D.F., Slingluff, C.L. Int. J. Cancer (1999) [Pubmed]
WikiGenes - Universities