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.

Kwon, Byoung S.; Chintamaneni, C; Kozak, Christine A.; Copeland, Neal G.; Gilbert, Debra J.; Jenkins, Nancy A.; Barton, D. E.; Francke, Uta; Kobayashi, Yvonne M.; Kim, Kack K.

doi:10.1073/pnas.88.20.9228

Cited by 147 publications

(94 citation statements)

References 33 publications

(26 reference statements)

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“…The above result allowed narrowing of the search to those genes that are (i) important in pigmentation and (ii) also proximal to microsatellite marker FH2537 on CFA10. SILV encodes a melanosomal protein important in pigmentation (28) and maps to HSA12q13-q14, which exhibits conservation of synteny with CFA10 (29). A single base insertion in SILV causes the silver phenotype in the mouse (23), and polymorphisms in this gene are associated with the dominant white, dun, and smoky plumage color variants in chickens (30).…”

Section: Resultsmentioning

confidence: 99%

Retrotransposon insertion in SILV is responsible for merle patterning of the domestic dog

Clark

Wahl

Rees

et al. 2006

Proc. Natl. Acad. Sci. U.S.A.

227

242

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Merle is a pattern of coloring observed in the coat of the domestic dog and is characterized by patches of diluted pigment. This trait is inherited in an autosomal, incompletely dominant fashion. Dogs heterozygous or homozygous for the merle locus exhibit a wide range of auditory and ophthalmologic abnormalities, which are similar to those observed for the human auditory-pigmentation disorder Waardenburg syndrome. Mutations in at least five genes have been identified as causative for Waardenburg syndrome; however, the genetic bases for all cases have not been determined. Linkage disequilibrium was identified for a microsatellite marker with the merle phenotype in the Shetland Sheepdog. The marker is located in a region of CFA10 that exhibits conservation of synteny with HSA12q13. This region of the human genome contains SILV, a gene important in mammalian pigmentation. Therefore, this gene was evaluated as a candidate for merle patterning. A short interspersed element insertion at the boundary of intron 10͞exon 11 was found, and this insertion segregates with the merle phenotype in multiple breeds. Another finding was deletions within the oligo(dA)-rich tail of the short interspersed element. Such deletions permit normal pigmentation. These data show that SILV is responsible for merle patterning and is associated with impaired function of the auditory and ophthalmologic systems. Although the mutant phenotype of SILV in the human is unknown, these results make it an intriguing candidate gene for human auditory-pigmentation disorders.short interspersed element ͉ pigmentation ͉ linkage disequilibrium

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Section: Resultsmentioning

confidence: 99%

Retrotransposon insertion in SILV is responsible for merle patterning of the domestic dog

Clark

Wahl

Rees

et al. 2006

Proc. Natl. Acad. Sci. U.S.A.

227

242

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“…An alignment of the deduced amino acid sequences of the WS5 protein and of the human melanoma antigen Pmel17 (Kwon et al, 1991), the mammalian protein displaying the highest amino acid sequence identity to WS5, is shown in Figure 3. The overall sequence identity between the human and the quail protein is 38%, whereas the identity between WS5 and the chicken Mmp115 protein (Mochii et al, 1991) is 77% (not shown).…”

Section: Specific Expression Of Ws5 In Myc-transformed Avian Fibroblastsmentioning

confidence: 99%

“…The amino acid sequence of quail WS5 shows the highest degree of identity (77%) with its presumed chicken homolog, the melanocytespecific glycoprotein Mmp115 (Mochii et al, 1991). The mammalian protein displaying the highest degree of sequence identity (38%) to WS5 is encoded by the human Pmel17 (or SILV) gene (Kwon et al, 1991). Although the melanocyte-specific type I transmembrane glycoprotein Pmel17 is known to have a central role in pigmentation, its precise function remains controversial (Theos et al, 2005).…”

Section: Ws5 a Direct Transcriptional Target Of Mycmentioning

confidence: 99%

WS5, a direct target of oncogenic transcription factor Myc, is related to human melanoma glycoprotein genes and has oncogenic potential

et al. 2006

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We have isolated a gene (WS5) that is specifically expressed at the mRNA and protein level in avian fibroblasts transformed by the v-myc oncogene of avian acute leukemia virus MC29. In a conditional cell transformation system, WS5 gene expression was tightly correlated with v-myc activation. The WS5 gene contains 11 exons, encoding a 733-amino acid protein with a transmembrane region and a polycystic kidney disease (PKD) domain. Near the transcriptional start site, the WS5 promoter contains a cluster of four binding sites for the Myc-Max complex and a binding site for transcription factor C/EBPa. Electrophoretic mobility shift assays and chromatin immunoprecipitation showed that Myc, Max and C/EBPa bind specifically to these sites. Functional promoter analyses revealed that both the Myc-binding site cluster and the C/EBPa-binding site are essential for strong transcriptional activation, and that Myc and C/EBPa synergistically activate the WS5 promoter. Ectopic expression of WS5 led to cell transformation documented by anchorage-independent growth. The human melanoma antigen Pmel17, a type I transmembrane glycoprotein, is the mammalian protein with the highest amino acid sequence identity (38%) to WS5. The Pmel17 gene is regulated by the MITF protein, a bHLHZip transcription factor with DNA binding specificities similar to those of Myc/Max. WS5 is also related to human glycoprotein GPNMB expressed in metastatic melanoma cells and implicated in the progression of brain and liver tumors.

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“…The Pmel17 gene was first discovered in mice in 1930 (15); although, it was not until 1991 when it was named and mapped to the silver locus (16). Because its overexpression in nonpigmented cells produces late endosomes exhibiting indistinguishable fibrous striations from those found in melanosomes (17), Pmel17 was implicated as the main protein component in melanosomal fibrils.…”

mentioning

confidence: 99%

Effects of pH on aggregation kinetics of the repeat domain of a functional amyloid, Pmel17

Pfefferkorn

McGlinchey²,

Lee³

2010

Proc. Natl. Acad. Sci. U.S.A.

114

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Pmel17 is a functional amyloidogenic protein whose fibrils act as scaffolds for pigment deposition in human skin and eyes. We have used the repeat domain (RPT, residues 315-444), an essential luminal polypeptide region of Pmel17, as a model system to study conformational changes from soluble unstructured monomers to β-sheet-containing fibrils. Specifically, we report on the effects of solution pH (4 → 7) mimicking pH conditions of melanosomes, acidic organelles where Pmel17 fibrils are formed. Local, secondary, and fibril structure were monitored via intrinsic Trp fluorescence, circular dichroism spectroscopy, and transmission electron microscopy, respectively. We find that W423 is a highly sensitive probe of amyloid assembly with spectral features reflecting local conformational and fibril morphological changes. A critical pH regime (5 AE 0.5) was identified for fibril formation suggesting the involvement of at least three carboxylic acids in the structural rearrangement necessary for aggregation. Moreover, we demonstrate that RPT fibril morphology can be transformed directly by changing solution pH. Based on these results, we propose that intramelanosomal pH regulates Pmel17 amyloid formation and its subsequent dissolution in vivo.fibril | fluorescence | melanosome | tryptophan | melanin

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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.

Cited by 147 publications

References 33 publications

Retrotransposon insertion in SILV is responsible for merle patterning of the domestic dog

Retrotransposon insertion in SILV is responsible for merle patterning of the domestic dog

WS5, a direct target of oncogenic transcription factor Myc, is related to human melanoma glycoprotein genes and has oncogenic potential

Effects of pH on aggregation kinetics of the repeat domain of a functional amyloid, Pmel17

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