This gene encodes a melanocyte-specific type I transmembrane glycoprotein. The encoded protein is enriched in melanosomes, which are the melanin-producing organelles in melanocytes, and plays an essential role in the structural organization of premelanosomes. This protein is involved in generating internal matrix fibers that define the transition from Stage I to Stage II melano... See more...

Aliases for PMEL Gene

Aliases for PMEL Gene

  • Premelanosome Protein 2 3 4 5
  • D12S53E 2 3 4
  • Melanocytes Lineage-Specific Antigen GP100 3 4
  • Melanoma-Associated ME20 Antigen 3 4
  • Silver Locus Protein Homolog 3 4
  • Melanocyte Protein Pmel 17 3 4
  • Melanocyte Protein PMEL 3 4
  • ME20-M 3 4
  • PMEL17 3 4
  • ME20M 3 4
  • Gp100 2 3
  • P100 3 4
  • SILV 3 4
  • P1 3 4
  • SI 2 3
  • Melanosomal Matrix Protein17 3
  • Silver (Mouse Homolog) Like 2
  • Melanocyte Protein Mel 17 3
  • Silver, Mouse, Homolog Of 3
  • Silver Homolog (Mouse) 2
  • Pmel17 2
  • ME20 3
  • PMEL 5
  • SIL 3

External Ids for PMEL Gene

Previous HGNC Symbols for PMEL Gene

  • SIL
  • SILV

Previous GeneCards Identifiers for PMEL Gene

  • GC12M056350
  • GC12M056352

Summaries for PMEL Gene

Entrez Gene Summary for PMEL Gene

  • This gene encodes a melanocyte-specific type I transmembrane glycoprotein. The encoded protein is enriched in melanosomes, which are the melanin-producing organelles in melanocytes, and plays an essential role in the structural organization of premelanosomes. This protein is involved in generating internal matrix fibers that define the transition from Stage I to Stage II melanosomes. This protein undergoes a complex pattern of prosttranslational processing and modification that is essential to the proper functioning of the protein. A secreted form of this protein that is released by proteolytic ectodomain shedding may be used as a melanoma-specific serum marker. Alternate splicing results in multiple transcript variants. [provided by RefSeq, Jan 2011]

GeneCards Summary for PMEL Gene

PMEL (Premelanosome Protein) is a Protein Coding gene. Diseases associated with PMEL include Vitiligo-Associated Multiple Autoimmune Disease Susceptibility 1 and Melanoma In Congenital Melanocytic Nevus. An important paralog of this gene is GPNMB.

UniProtKB/Swiss-Prot Summary for PMEL Gene

  • Plays a central role in the biogenesis of melanosomes. Involved in the maturation of melanosomes from stage I to II. The transition from stage I melanosomes to stage II melanosomes involves an elongation of the vesicle, and the appearance within of distinct fibrillar structures. Release of the soluble form, ME20-S, could protect tumor cells from antibody mediated immunity.

Gene Wiki entry for PMEL Gene

No data available for CIViC Summary , Tocris Summary , PharmGKB "VIP" Summary , Rfam classification and piRNA Summary for PMEL Gene

Genomics for PMEL Gene

GeneHancer (GH) Regulatory Elements Pubs

Promoters and enhancers for PMEL Gene
- Elite GeneHancer and/or Elite GeneHancer-gene association Download GeneHancer data from 2017 publication | Request up-to-date GeneHancer data (full dataset)

GeneHancers around PMEL on the GeneHancer Hub at the UCSC Golden Path

Cistromic (ChIP-Seq) regulation report from SPP (The Signaling Pathways Project) for PMEL

Genomic Locations for PMEL Gene

Genomic Locations for PMEL Gene
chr12:55,954,105-55,973,317
(GRCh38/hg38)
Size:
19,213 bases
Orientation:
Minus strand
chr12:56,347,889-56,367,101
(GRCh37/hg19)
Size:
19,213 bases
Orientation:
Minus strand

Genomic View for PMEL Gene

Genes around PMEL on UCSC Golden Path with GeneCards custom track

Cytogenetic band:
PMEL Gene in genomic location: bands according to Ensembl, locations according to GeneLoc (and/or Entrez Gene and/or Ensembl if different)
Genomic Location for PMEL Gene
GeneLoc Logo Genomic Neighborhood Exon StructureGene Density

RefSeq DNA sequence for PMEL Gene

Proteins for PMEL Gene

  • Protein details for PMEL Gene (UniProtKB/Swiss-Prot)

    Protein Symbol:
    P40967-PMEL_HUMAN
    Recommended name:
    Melanocyte protein PMEL
    Protein Accession:
    P40967
    Secondary Accessions:
    • B3KS57
    • B7Z6D7
    • Q12763
    • Q14448
    • Q14817
    • Q16565

    Protein attributes for PMEL Gene

    Size:
    661 amino acids
    Molecular mass:
    70255 Da
    Quaternary structure:
    • Heterooligomer; disulfide-linked heterooligomers of M-alpha and M-beta. Interacts with MLANA. Interacts (via luminal domain) with CD63; this is important for normal sorting of the luminal domain after proteolytic processing.
    SequenceCaution:
    • Sequence=AAA35930.1; Type=Erroneous initiation; Note=Truncated N-terminus.; Evidence={ECO:0000305}; Sequence=AAA35930.1; Type=Frameshift; Evidence={ECO:0000305};

    Three dimensional structures from OCA and Proteopedia for PMEL Gene

    Alternative splice isoforms for PMEL Gene

    UniProtKB/Swiss-Prot:

neXtProt entry for PMEL Gene

Post-translational modifications for PMEL Gene

  • A small amount of P1/P100 (major form) undergoes glycosylation to yield P2/P120 (minor form). P2 is cleaved by a furin-like proprotein convertase (PC) in a pH-dependent manner in a post-Golgi, prelysosomal compartment into two disulfide-linked subunits: a large lumenal subunit, M-alpha/ME20-S, and an integral membrane subunit, M-beta. Despite cleavage, only a small fraction of M-alpha is secreted, whereas most M-alpha and M-beta remain associated with each other intracellularly. M-alpha is further processed to M-alpha N and M-alpha C. M-alpha C further undergoes processing to yield M-alpha C1 and M-alpha C3 (M-alpha C2 in the case of PMEL17-is or PMEL17-ls). Formation of intralumenal fibrils in the melanosomes requires the formation of M-alpha that becomes incorporated into the fibrils. Stage II melanosomes harbor only Golgi-modified Pmel17 fragments that are derived from M-alpha and that bear sialylated O-linked oligosaccharides.
  • N-glycosylated. O-glycosylated; contains sialic acid.
  • Glycosylation at Asn81, Asn106, Asn111, Asn321, and Asn568
  • Modification sites at PhosphoSitePlus

Antibody Products

No data available for DME Specific Peptides for PMEL Gene

Domains & Families for PMEL Gene

Gene Families for PMEL Gene

Human Protein Atlas (HPA):
  • Predicted intracellular proteins
  • Predicted membrane proteins

Protein Domains for PMEL Gene

InterPro:
Blocks:
  • PKD
ProtoNet:

Suggested Antigen Peptide Sequences for PMEL Gene

GenScript: Design optimal peptide antigens:
  • Silver locus protein homolog (PMEL_HUMAN)

Graphical View of Domain Structure for InterPro Entry

P40967

UniProtKB/Swiss-Prot:

PMEL_HUMAN :
  • The RPT domain is essential for the generation of the fibrillar matrix of melanosomes.
  • Belongs to the PMEL/NMB family.
Domain:
  • The RPT domain is essential for the generation of the fibrillar matrix of melanosomes.
  • The lumenal domain is necessary for correct processing and trafficking to melanosomes.
Family:
  • Belongs to the PMEL/NMB family.
genes like me logo Genes that share domains with PMEL: view

Function for PMEL Gene

Molecular function for PMEL Gene

UniProtKB/Swiss-Prot Function:
Plays a central role in the biogenesis of melanosomes. Involved in the maturation of melanosomes from stage I to II. The transition from stage I melanosomes to stage II melanosomes involves an elongation of the vesicle, and the appearance within of distinct fibrillar structures. Release of the soluble form, ME20-S, could protect tumor cells from antibody mediated immunity.

Phenotypes From GWAS Catalog for PMEL Gene

Gene Ontology (GO) - Molecular Function for PMEL Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0005515 protein binding IPI 15695812
GO:0042802 identical protein binding IPI 19666488
genes like me logo Genes that share ontologies with PMEL: view
genes like me logo Genes that share phenotypes with PMEL: view

Animal Models for PMEL Gene

MGI Knock Outs for PMEL:
  • Pmel Pmel<tm1b(EUCOMM)Wtsi>
  • Pmel Pmel<tm1.1Sson>

Animal Model Products

CRISPR Products

miRNA for PMEL Gene

miRTarBase miRNAs that target PMEL

Inhibitory RNA Products

  • Search GeneCopoeia for shRNA, lentivirus and/or AAV clone products for PMEL

No data available for Enzyme Numbers (IUBMB) , Human Phenotype Ontology , Transcription Factor Targets and HOMER Transcription for PMEL Gene

Localization for PMEL Gene

Subcellular locations from UniProtKB/Swiss-Prot for PMEL Gene

Endoplasmic reticulum membrane. Single-pass type I membrane protein. Golgi apparatus. Melanosome. Endosome, multivesicular body. Note=Identified by mass spectrometry in melanosome fractions from stage I to stage IV. Localizes predominantly to intralumenal vesicles (ILVs) within multivesicular bodies. Associates with ILVs found within the lumen of premelanosomes and melanosomes and particularly in compartments that serve as precursors to the striated stage II premelanosomes.
[M-alpha]: Secreted.

Subcellular locations from

COMPARTMENTS
Extracellular space Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi Apparatus Nucleus Mitochondrion 0 1 2 3 4 5 Confidence
COMPARTMENTS Subcellular localization image for PMEL gene
Compartment Confidence
plasma membrane 5
extracellular 5
endoplasmic reticulum 5
endosome 5
golgi apparatus 5
cytoskeleton 2
mitochondrion 2
nucleus 2
cytosol 2
lysosome 2

Subcellular locations from the

Human Protein Atlas (HPA)
  • Endoplasmic reticulum (3)
  • Golgi apparatus (3)
See all subcellular structures

Gene Ontology (GO) - Cellular Components for PMEL Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0005576 extracellular region IEA --
GO:0005768 endosome IEA --
GO:0005771 multivesicular body IEA --
GO:0005783 endoplasmic reticulum IEA,IDA --
GO:0005789 endoplasmic reticulum membrane IEA,IDA 15695812
genes like me logo Genes that share ontologies with PMEL: view

Pathways & Interactions for PMEL Gene

PathCards logo

SuperPathways for PMEL Gene

No Data Available

SIGNOR curated interactions for PMEL Gene

Is activated by:

Gene Ontology (GO) - Biological Process for PMEL Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0032438 melanosome organization IBA,IDA 11694580
GO:0042438 melanin biosynthetic process IEA --
genes like me logo Genes that share ontologies with PMEL: view

No data available for Pathways by source for PMEL Gene

Drugs & Compounds for PMEL Gene

(1) Drugs for PMEL Gene - From: Novoseek

Name Status Disease Links Group Role Mechanism of Action Clinical Trials

(2) Additional Compounds for PMEL Gene - From: Novoseek

Name Synonyms Role CAS Number PubChem IDs PubMed IDs
genes like me logo Genes that share compounds with PMEL: view

Transcripts for PMEL Gene

mRNA/cDNA for PMEL Gene

6 REFSEQ mRNAs :
12 NCBI additional mRNA sequence :
19 Ensembl transcripts including schematic representations, and UCSC links to gene/alias where relevant :

CRISPR Products

Inhibitory RNA Products

  • Search GeneCopoeia for shRNA, lentivirus and/or AAV clone products for PMEL

Alternative Splicing Database (ASD) splice patterns (SP) for PMEL Gene

ExUns: 1 ^ 2 ^ 3a · 3b · 3c ^ 4 ^ 5a · 5b ^ 6a · 6b · 6c · 6d ^ 7a · 7b · 7c ^ 8a · 8b ^ 9a · 9b ^ 10 ^ 11a · 11b ^ 12a · 12b · 12c ^ 13a ·
SP1: - - - -
SP2: - - -
SP3: - - -
SP4: -
SP5: - - - - - - - - - - - - - - - -
SP6: - - - - - -
SP7: -
SP8: - - -
SP9: - - - - -
SP10: - - - - - - -
SP11: - - -
SP12: -
SP13: -
SP14: - - - - -
SP15: - - - -
SP16:
SP17:

ExUns: 13b ^ 14 ^ 15a · 15b · 15c ^ 16
SP1: -
SP2: -
SP3:
SP4: -
SP5: -
SP6:
SP7:
SP8:
SP9:
SP10:
SP11:
SP12:
SP13:
SP14:
SP15:
SP16:
SP17:

Relevant External Links for PMEL Gene

GeneLoc Exon Structure for
PMEL

Expression for PMEL Gene

mRNA expression in normal human tissues from GTEx, Illumina, BioGPS, and SAGE for PMEL Gene

mRNA differential expression in normal tissues according to GTEx for PMEL Gene

This gene is overexpressed in Cervix - Ectocervix (x22.0), Skin - Not Sun Exposed (Suprapubic) (x9.2), and Skin - Sun Exposed (Lower leg) (x6.6).

Protein differential expression in normal tissues from HIPED for PMEL Gene

This gene is overexpressed in Hair follicle (69.0).

Integrated Proteomics: protein expression in normal tissues and cell lines from ProteomicsDB and MOPED for PMEL Gene



Protein tissue co-expression partners for PMEL Gene

- Elite partner

Transcriptomic regulation report from SPP (The Signaling Pathways Project) for PMEL

SOURCE GeneReport for Unigene cluster for PMEL Gene:

Hs.95972

mRNA Expression by UniProt/SwissProt for PMEL Gene:

P40967-PMEL_HUMAN
Tissue specificity: Preferentially expressed in melanomas. Some expression was found in dysplastic nevi. Not found in normal tissues nor in carcinomas. Normally expressed at low levels in quiescent adult melanocytes but overexpressed by proliferating neonatal melanocytes and during tumor growth.

Evidence on tissue expression from TISSUES for PMEL Gene

  • Skin(5)
  • Spleen(4.6)
  • Eye(4.3)
  • Lymph node(3.1)
  • Nervous system(3.1)
  • Blood(3)
  • Intestine(2.3)
  • Kidney(2.2)
  • Liver(2.1)
  • Bone marrow(2.1)
genes like me logo Genes that share expression patterns with PMEL: view

No data available for Phenotype-based relationships between genes and organs from Gene ORGANizer for PMEL Gene

Orthologs for PMEL Gene

This gene was present in the common ancestor of chordates.

Orthologs for PMEL Gene

Organism Taxonomy Gene Similarity Type Details
Chimpanzee
(Pan troglodytes)
Mammalia PMEL 30 31
  • 99.55 (n)
OneToOne
Dog
(Canis familiaris)
Mammalia PMEL 30
  • 86.04 (n)
PMEL17 31
  • 73 (a)
OneToOne
Cow
(Bos Taurus)
Mammalia PMEL 30
  • 85.68 (n)
PMEL17 31
  • 80 (a)
OneToOne
Mouse
(Mus musculus)
Mammalia Pmel 30 17 31
  • 83.81 (n)
OneToOne
Rat
(Rattus norvegicus)
Mammalia Pmel 30
  • 83.69 (n)
Platypus
(Ornithorhynchus anatinus)
Mammalia PMEL 31
  • 53 (a)
OneToOne
Chicken
(Gallus gallus)
Aves PMEL 30 31
  • 54.76 (n)
OneToOne
Lizard
(Anolis carolinensis)
Reptilia PMEL 31
  • 35 (a)
OneToOne
Tropical Clawed Frog
(Silurana tropicalis)
Amphibia pmel 30
  • 53.75 (n)
Zebrafish
(Danio rerio)
Actinopterygii pmela 30 31
  • 52.91 (n)
OneToMany
pmelb 31
  • 32 (a)
OneToMany
Species where no ortholog for PMEL was found in the sources mined by GeneCards:
  • A. gosspyii yeast (Eremothecium gossypii)
  • Actinobacteria (Mycobacterium tuberculosis)
  • African clawed frog (Xenopus laevis)
  • African malaria mosquito (Anopheles gambiae)
  • Alicante grape (Vitis vinifera)
  • Alpha proteobacteria (Wolbachia pipientis)
  • Amoeba (Dictyostelium discoideum)
  • Archea (Pyrococcus horikoshii)
  • Baker's yeast (Saccharomyces cerevisiae)
  • Barley (Hordeum vulgare)
  • Beta proteobacteria (Neisseria meningitidis)
  • Bread mold (Neurospora crassa)
  • Chromalveolata (Phytophthora infestans)
  • Common water flea (Daphnia pulex)
  • Corn (Zea mays)
  • E. coli (Escherichia coli)
  • Filamentous fungi (Aspergillus nidulans)
  • Firmicute Bacteria (Streptococcus pneumoniae)
  • Fission Yeast (Schizosaccharomyces pombe)
  • Fruit Fly (Drosophila melanogaster)
  • Green Algae (Chlamydomonas reinhardtii)
  • Honey Bee (Apis mellifera)
  • K. Lactis Yeast (Kluyveromyces lactis)
  • Loblloly Pine (Pinus taeda)
  • Malaria Parasite (Plasmodium falciparum)
  • Medicago Trunc (Medicago Truncatula)
  • Moss (Physcomitrella patens)
  • Oppossum (Monodelphis domestica)
  • Orangutan (Pongo pygmaeus)
  • Pig (Sus scrofa)
  • Rainbow Trout (Oncorhynchus mykiss)
  • Rice (Oryza sativa)
  • Rice Blast Fungus (Magnaporthe grisea)
  • Schistosome Parasite (Schistosoma mansoni)
  • Sea Anemone (Nematostella vectensis)
  • Sea Vase (Ciona intestinalis)
  • Sea Squirt (Ciona savignyi)
  • Sea Urchin (Strongylocentrotus purpuratus)
  • Sorghum (Sorghum bicolor)
  • Soybean (Glycine max)
  • Stem Rust Fungus (Puccinia graminis)
  • Sugarcane (Saccharum officinarum)
  • Thale Cress (Arabidopsis thaliana)
  • Tomato (Lycopersicon esculentum)
  • Toxoplasmosis (Toxoplasma gondii)
  • Trichoplax (Trichoplax adhaerens)
  • Wheat (Triticum aestivum)
  • Worm (Caenorhabditis elegans)

Evolution for PMEL Gene

ENSEMBL:
Gene Tree for PMEL (if available)
TreeFam:
Gene Tree for PMEL (if available)
Aminode:
Evolutionary constrained regions (ECRs) for PMEL: view image

Paralogs for PMEL Gene

Paralogs for PMEL Gene

(1) SIMAP similar genes for PMEL Gene using alignment to 11 proteins:

  • PMEL_HUMAN
  • F5H2A6_HUMAN
  • F8VUB1_HUMAN
  • F8VXH8_HUMAN
  • F8VYZ1_HUMAN
  • F8VZC6_HUMAN
  • F8VZV2_HUMAN
  • F8W1D1_HUMAN
  • H0YIJ2_HUMAN
  • J3KP45_HUMAN
  • L8ECD6_HUMAN
genes like me logo Genes that share paralogs with PMEL: view

Variants for PMEL Gene

Sequence variations, with clinical significance, from ClinVar and Humsavar, with links to dbSNP for PMEL Gene

SNP ID Clinical significance and condition Chr 12 pos Variation AA Info Type
708945 Benign: not provided 55,957,617(-) T/C MISSENSE_VARIANT
713129 Benign: not provided 55,956,963(-) G/A MISSENSE_VARIANT
737198 Likely Benign: not provided 55,954,322(-) G/A SYNONYMOUS_VARIANT
739674 Likely Benign: not provided 55,957,274(-) T/C SYNONYMOUS_VARIANT
769389 Benign: not provided 55,957,193(-) C/G MISSENSE_VARIANT

Additional dbSNP identifiers (rs#s) for PMEL Gene

Structural Variations from Database of Genomic Variants (DGV) for PMEL Gene

Variant ID Type Subtype PubMed ID
nsv1051961 CNV gain 25217958
nsv819836 CNV loss 19587683
nsv832424 CNV loss 17160897

Variation tolerance for PMEL Gene

Residual Variation Intolerance Score: 51.5% of all genes are more intolerant (likely to be disease-causing)
Gene Damage Index Score: 4.85; 67.28% of all genes are more intolerant (likely to be disease-causing)

Additional Variant Information for PMEL Gene

Human Gene Mutation Database (HGMD)
PMEL
SNPedia medical, phenotypic, and genealogical associations of SNPs for
PMEL

SNP Genotyping and Copy Number Assay Products

No data available for Polymorphic Variants from UniProtKB/Swiss-Prot for PMEL Gene

Disorders for PMEL Gene

MalaCards: The human disease database

(27) MalaCards diseases for PMEL Gene - From: DISEASES, Novoseek, and GeneCards

Disorder Aliases PubMed IDs
vitiligo-associated multiple autoimmune disease susceptibility 1
  • vamas1
melanoma in congenital melanocytic nevus
  • malignant melanoma in congenital melanocytic nevus
gallbladder melanoma
  • malignant melanoma of gallbladder
skin melanoma
  • melanoma, cutaneous malignant
vogt-koyanagi-harada disease
  • harada's disease
- elite association - COSMIC cancer census association via MalaCards
Search PMEL in MalaCards View complete list of genes associated with diseases
genes like me logo Genes that share disorders with PMEL: view

No data available for UniProtKB/Swiss-Prot and Genatlas for PMEL Gene

Publications for PMEL Gene

  1. Premelanosome amyloid-like fibrils are composed of only golgi-processed forms of Pmel17 that have been proteolytically processed in endosomes. (PMID: 17991747) Harper DC … Marks MS (The Journal of biological chemistry 2008) 3 4 23
  2. MART-1 is required for the function of the melanosomal matrix protein PMEL17/GP100 and the maturation of melanosomes. (PMID: 15695812) Hoashi T … Hearing VJ (The Journal of biological chemistry 2005) 3 4 23
  3. Epitope mapping of the melanosomal matrix protein gp100 (PMEL17): rapid processing in the endoplasmic reticulum and glycosylation in the early Golgi compartment. (PMID: 15096515) Yasumoto K … Hearing VJ (The Journal of biological chemistry 2004) 3 4 23
  4. Proprotein convertase cleavage liberates a fibrillogenic fragment of a resident glycoprotein to initiate melanosome biogenesis. (PMID: 12732614) Berson JF … Marks MS (The Journal of cell biology 2003) 3 4 23
  5. A novel splice variant of Pmel17 expressed by human melanocytes and melanoma cells lacking some of the internal repeats. (PMID: 14632201) Nichols SE … Marks MS (The Journal of investigative dermatology 2003) 3 4 23

Products for PMEL Gene

Sources for PMEL Gene