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FLASH GENE
Symbol PMEL contributors: mct/npt - updated : 18-03-2015
HGNC name premelanosome protein
HGNC id 10880
Location 12q13.2      Physical location : -
Synonym name
  • melanocyte protein mel17
  • 95 kDa melanocyte-specific secreted glycoprotein
  • melanosome fibril protein 17
  • silver (mouse homolog) like
  • melanocyte lineage-specific antigen GP100
  • melanosomal matrix protein17
  • silver homolog (mouse)
  • Synonym symbol(s) D12S53E, PMEL17, SI, SIL, PM17, ME20, ME20M, gp100, SILV
    DNA
    TYPE functioning gene
    STRUCTURE 12.51 kb     11 Exon(s)
    MAPPING cloned Y linked   status confirmed
    RNA
    TRANSCRIPTS type messenger
    identificationnb exonstypebpproduct
    ProteinkDaAAspecific expressionYearPubmed
    11 - 2181 - 668 all melanocytic cells 2003 14632201
  • also called PMEL17s
  • containing a deletion within the lumenal domain tandem repeat region
  • localizes similarly to late endosomes when expressed ectopically in nonpigment cells
  • truncation of the repeat region alters either fibrillogenic activity or the interaction with melanin intermediates
  • 9 - 1902 - 575 - 2003 14632201
  • also called PMEL17l mature
  • sorted directly to melanosomes
  • 12 splicing 2143 100 661 - 2003 14632201
  • also called PMEL17i
  • less glycosylated form of SILV (termed iPmel17) is sorted via the plasma membrane in a manner distinct from mature SILV (termed mPmel17), which is sorted directly to melanosomes
  • glycosylated differently in the Golgi and it is sorted through the secretory pathway (Valencia 2007)
  • EXPRESSION
    Type widely
       expressed in (based on citations)
    organ(s)
    SystemOrgan level 1Organ level 2Organ level 3Organ level 4LevelPubmedSpeciesStageRna symbol
    Skin/Tegumentskin   predominantly
    Visualeye   highly
    cells
    SystemCellPubmedSpeciesStageRna symbol
    Skin/Tegumentmelanocyte Homo sapiens
    cell lineage
    cell lines melanoma cell lines
    fluid/secretion
    at STAGE
    physiological period neonatal
    Text highly in neonatal proliferating melanocytes
    PROTEIN
    PHYSICAL PROPERTIES
    STRUCTURE
    motifs/domains
  • an N-terminal region (NTR) lacking any revealing homology, and a downstream domain with homology to a polycystic kidney disease-1 repeat (Watt 2009), N-terminal region essential for the mature fibrils formation
  • a polycystic kidney disease domain (PKD) (integrity of the junction between the N-terminal region and the polycystic kidney disease-like domain is highly crucial for endoplasmic reticulum export, subcellular targeting, and fibril formation and thus for establishing functional melanosomes) (Leonhardt 2010)
  • a repeat (RPT) region with 10 imperfect copies of the sequence “pt.e.gttp.qv.,” necessary for fiber formation and promoting eumelanin formation (McGlinchey 2009), RPT domain playing a regulatory role in timing amyloid conversion, suggesting that fibril formation might be physically linked with multivesicular body sorting (Watt 2009)
  • a kringle-like domain (KRG),
  • a single transmembrane domain
  • a large luminal domain with several distinct regions
  • a short C-terminal cytoplasmic domain (McGlinchey 2009)
  • conjugated FlavoP
    HOMOLOGY
    interspecies homolog to murine silver
    Homologene
    FAMILY
  • Pmel-17/NMB family
  • CATEGORY enzyme
    SUBCELLULAR LOCALIZATION extracellular
        plasma membrane
        intracellular
    intracellular,cytoplasm,organelle,membrane
    intracellular,cytoplasm,organelle,endoplasmic reticulum
    intracellular,cytoplasm,organelle,Golgi
    text
  • type I integral membrane glycoprotein that localizes to the lumen of melanosome precursors, specifically expressed in melanocytes and melanoma
  • localizes to melanosomes, where it forms a fibrillar matrix that serves for the sequestration of potentially toxic reaction intermediates of melanin synthesis and deposition of the pigment (Leonhardt 2010)
  • integral membrane protein that undergoes export from the endoplasmic reticulum to the Golgi apparatus where it is glycosylated and, ultimately, trafficked to the melanosome
  • proteolytic fragments from PMEL form fibrils upon which melanin is deposited in melanosomes
  • basic FUNCTION
  • involved in a late step of melanin biosynthesis
  • playing a crucial role in the morphogenesis of melanosome precursors and in the pigmentation
  • mediates the early steps in the formation of melanosomes, the subcellular organelles of melanocytes in which melanin pigments are synthesized and stored (Watt 2009)
  • melanocyte/melanoma-specific protein having a function for melanosome biogenesis (Leonhardt 2010)
  • exerts a critical function within the melanosome by assembling into a fibrillar sheet structure, onto which potentially toxic reaction intermediates of the melanin synthesis pathway as well as the mature pigment get deposited and concentrate (Leonhardt 2010)
  • pigment cell-specific protein that forms physiological amyloid fibrils upon which melanins ultimately deposit in the lumen of the pigment organelle, the melanosome
  • melanocyte/melanoma-specific glycoprotein that plays a critical role in melanosome development by forming a fibrillar amyloid matrix in the organelle for melanin deposition
  • important protein for pigmentation in human skin and eyes
  • CELLULAR PROCESS
    PHYSIOLOGICAL PROCESS
    PATHWAY
    metabolism
    signaling
    a component
    INTERACTION
    DNA
    RNA
    small molecule
    protein
  • interacting with MLANA (indispensable for SILV function and thus plays an important role in regulating mammalian pigmentation)
  • BACE2 cleaves the integral membrane form of PMEL within the juxtamembrane domain, releasing the PMEL luminal domain into endosomal precursors for the formation of amyloid fibrils and downstream melanosome morphogenesis
  • loss of function of GPR143 leading to a significant reduction in expression of PMEL, a major melanosomal structural protein
  • APOE regulates the endosomal formation of PMEL amyloid fibrils
  • cell & other
    REGULATION
    Other regulated by MITF
    regulated by RAB7A (regulates maturation of melanosomal matrix protein)(Kawakami 2008)
    ASSOCIATED DISORDERS
    corresponding disease(s)
    Other morbid association(s)
    TypeGene ModificationChromosome rearrangementProtein expressionProtein Function
    tumoral     --over  
    in melanoma (during tumor growth)
    constitutional     --over  
    of autoantibodies in vitiligo
    constitutional       loss of function
    reduces both the basal expression and cAMP-dependent induction of the microphthalmia-associated transcription factor (MITF), the master regulator of melanocyte differentiation
    Susceptibility
    Variant & Polymorphism
    Candidate gene
    Marker
    Therapy target
    SystemTypeDisorderPubmed
    cancerskin 
    attractive target for antibody drug conjugate (ADC) therapy in melanoma
    ANIMAL & CELL MODELS
  • Pmel-/- mice are fully viable, fertile, and display no obvious developmental defects but melanosomes within melanocytes are spherical in contrast to the oblong shape present in wild-type animals