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PMEL premelanosome protein [ Homo sapiens (human) ]

Gene ID: 6490, updated on 11-Apr-2024

Summary

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Official Symbol
PMELprovided by HGNC
Official Full Name
premelanosome proteinprovided by HGNC
Primary source
HGNC:HGNC:10880
See related
Ensembl:ENSG00000185664 MIM:155550; AllianceGenome:HGNC:10880
Gene type
protein coding
RefSeq status
REVIEWED
Organism
Homo sapiens
Lineage
Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo
Also known as
P1; SI; SIL; ME20; P100; SILV; HMB45; ME20M; gp100; HMB-45; ME20-M; PMEL17; D12S53E
Summary
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]
Expression
Biased expression in skin (RPKM 37.5), testis (RPKM 2.4) and 1 other tissue See more
Orthologs
mouse all
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Genomic context

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Location:
12q13.2
Exon count:
12
Annotation release Status Assembly Chr Location
RS_2023_10 current GRCh38.p14 (GCF_000001405.40) 12 NC_000012.12 (55954105..55966709, complement)
RS_2023_10 current T2T-CHM13v2.0 (GCF_009914755.1) 12 NC_060936.1 (55921167..55933772, complement)
105.20220307 previous assembly GRCh37.p13 (GCF_000001405.25) 12 NC_000012.11 (56347889..56360493, complement)

Chromosome 12 - NC_000012.12Genomic Context describing neighboring genes Neighboring gene PYM homolog 1, exon junction complex associated factor Neighboring gene uncharacterized LOC124902941 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 4539 Neighboring gene NANOG-H3K27ac-H3K4me1 hESC enhancer GRCh37_chr12:56320788-56321368 Neighboring gene NANOG-H3K27ac-H3K4me1 hESC enhancer GRCh37_chr12:56321369-56321949 Neighboring gene diacylglycerol kinase alpha Neighboring gene H3K4me1 hESC enhancer GRCh37_chr12:56333724-56334224 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr12:56334225-56334725 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr12:56350689-56351190 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr12:56354315-56354815 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 6464 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 6465 Neighboring gene cyclin dependent kinase 2 Neighboring gene RAB13, member RAS oncogene family pseudogene Neighboring gene RAB5B, member RAS oncogene family

Genomic regions, transcripts, and products

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Go to nucleotide: Graphics FASTA GenBank

Expression

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  • Project title: HPA RNA-seq normal tissues
  • Description: RNA-seq was performed of tissue samples from 95 human individuals representing 27 different tissues in order to determine tissue-specificity of all protein-coding genes
  • BioProject: PRJEB4337
  • Publication: PMID 24309898
  • Analysis date: Wed Apr 4 07:08:55 2018

Bibliography

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Related articles in PubMed

  1. PMEL as a Prognostic Biomarker and Negatively Associated With Immune Infiltration in Skin Cutaneous Melanoma (SKCM). Zhang S, et al. J Immunother, 2021 Jul-Aug 01. PMID 34028390, Free PMC Article
  2. Identification of critical amino acid residues in the regulatory N-terminal domain of PMEL. Mitchell SM, et al. Sci Rep, 2021 Apr 8. PMID 33833328, Free PMC Article
  3. Hofmeister Ions Modulate the Autocatalytic Amyloidogenesis of an Intrinsically Disordered Functional Amyloid Domain via Unusual Biphasic Kinetics. Dogra P, et al. J Mol Biol, 2020 Nov 20. PMID 33068637
  4. Modulating functional amyloid formation via alternative splicing of the premelanosomal protein PMEL17. Dean DN, et al. J Biol Chem, 2020 May 22. PMID 32277052, Free PMC Article
  5. pH-Dependent fibril maturation of a Pmel17 repeat domain isoform revealed by tryptophan fluorescence. Dean DN, et al. Biochim Biophys Acta Proteins Proteom, 2019 Oct. PMID 30716507, Free PMC Article

See all (92) citations in PubMed

GeneRIFs: Gene References Into Functions

What's a GeneRIF?
  1. Biogenesis of fibrils requires C-mannosylation of PMEL.
    Title: Biogenesis of fibrils requires C-mannosylation of PMEL.
  2. PMEL as a Prognostic Biomarker and Negatively Associated With Immune Infiltration in Skin Cutaneous Melanoma (SKCM).
    Title: PMEL as a Prognostic Biomarker and Negatively Associated With Immune Infiltration in Skin Cutaneous Melanoma (SKCM).
  3. Identification of critical amino acid residues in the regulatory N-terminal domain of PMEL.
    Title: Identification of critical amino acid residues in the regulatory N-terminal domain of PMEL.
  4. Functional Domains and Evolutionary History of the PMEL and GPNMB Family Proteins.
    Title: Functional Domains and Evolutionary History of the PMEL and GPNMB Family Proteins.
  5. Hofmeister Ions Modulate the Autocatalytic Amyloidogenesis of an Intrinsically Disordered Functional Amyloid Domain via Unusual Biphasic Kinetics.
    Title: Hofmeister Ions Modulate the Autocatalytic Amyloidogenesis of an Intrinsically Disordered Functional Amyloid Domain via Unusual Biphasic Kinetics.
  6. Modulating functional amyloid formation via alternative splicing of the premelanosomal protein PMEL17.
    Title: Modulating functional amyloid formation via alternative splicing of the premelanosomal protein PMEL17.
  7. Defining an amyloid link Between Parkinson's disease and melanoma.
    Title: Defining an amyloid link Between Parkinson's disease and melanoma.
  8. pH-Dependent fibril maturation of a Pmel17 repeat domain isoform revealed by tryptophan fluorescence.
    Title: pH-Dependent fibril maturation of a Pmel17 repeat domain isoform revealed by tryptophan fluorescence.
  9. These results can give insight into how lysophospholipids might influence repeat domain of Pmel17 aggregation and can give some understanding of general protein-lipid interactions of amyloidogenic proteins.
    Title: Lysophospholipids induce fibrillation of the repeat domain of Pmel17 through intermediate core-shell structures.
  10. This report establishes variation in PMEL as a cause of pigment dispersion syndrom/Pigmentary glaucoma based on several mutually supporting lines of evidence. First, WES of two families affected by PDS/PG and having pedigrees consistent with dominant modes of inheritance led to identification of heterozygous non-synonymous variants in PMEL. We identified seven associated non-synonymous variants.
    Title: Non-Synonymous variants in premelanosome protein (PMEL) cause ocular pigment dispersion and pigmentary glaucoma.
Submit: New GeneRIF Correction See all GeneRIFs (62)

Phenotypes

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Find tests for this gene in the NIH Genetic Testing Registry (GTR)

Review eQTL and phenotype association data in this region using PheGenI

EBI GWAS Catalog

Description
Association analyses identify three susceptibility Loci for vitiligo in the Chinese Han population.
EBI GWAS Catalog
Genome-wide association study identifies three new susceptibility loci for adult asthma in the Japanese population.
EBI GWAS Catalog

Variation

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See variants in ClinVar

See studies and variants in dbVar

See Variation Viewer (GRCh37.p13)

See Variation Viewer (GRCh38)

Genotypes

Pathways from PubChem

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Interactions

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Products Interactant Other Gene Complex Source Pubs Description

General gene information

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Markers

Homology

Gene Ontology Provided by GOA

Function Evidence Code Pubs
enables identical protein binding IPI
Inferred from Physical Interaction
more info
 PubMed 
enables protein binding IPI
Inferred from Physical Interaction
more info
 PubMed 
Process Evidence Code Pubs
involved_in melanin biosynthetic process IEA
Inferred from Electronic Annotation
more info
  
involved_in melanosome organization IBA
Inferred from Biological aspect of Ancestor
more info
  
involved_in melanosome organization IDA
Inferred from Direct Assay
more info
 PubMed 
involved_in positive regulation of melanin biosynthetic process IEA
Inferred from Electronic Annotation
more info
  
Component Evidence Code Pubs
located_in Golgi apparatus IDA
Inferred from Direct Assay
more info
 PubMed 
located_in cis-Golgi network membrane IDA
Inferred from Direct Assay
more info
 PubMed 
located_in endoplasmic reticulum IDA
Inferred from Direct Assay
more info
  
located_in endoplasmic reticulum membrane IDA
Inferred from Direct Assay
more info
 PubMed 
located_in extracellular exosome IDA
Inferred from Direct Assay
more info
 PubMed 
is_active_in melanosome IBA
Inferred from Biological aspect of Ancestor
more info
  
located_in melanosome IDA
Inferred from Direct Assay
more info
 PubMed 
located_in melanosome membrane IDA
Inferred from Direct Assay
more info
 PubMed 
located_in multivesicular body membrane IDA
Inferred from Direct Assay
more info
 PubMed 
located_in multivesicular body, internal vesicle IDA
Inferred from Direct Assay
more info
 PubMed 
is_active_in plasma membrane IBA
Inferred from Biological aspect of Ancestor
more info
  
located_in plasma membrane TAS
Traceable Author Statement
more info
 PubMed 

General protein information

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Preferred Names
melanocyte protein PMEL
Names
melanocyte protein Pmel 17
melanocyte protein mel 17
melanocytes lineage-specific antigen GP100
melanoma-associated ME20 antigen
melanosomal matrix protein17
silver locus protein homolog
silver, mouse, homolog of

NCBI Reference Sequences (RefSeq)

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RefSeqs maintained independently of Annotated Genomes

These reference sequences exist independently of genome builds. Explain

These reference sequences are curated independently of the genome annotation cycle, so their versions may not match the RefSeq versions in the current genome build. Identify version mismatches by comparing the version of the RefSeq in this section to the one reported in Genomic regions, transcripts, and products above.

Genomic

  1. NG_028086.1 RefSeqGene

    Range
    5671..17608
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

  1. NM_001200053.1 → NP_001186982.1  melanocyte protein PMEL isoform 2 precursor

    Status: REVIEWED

    Description
    Transcript Variant: This variant (2) lacks two exons in the coding region, compared to variant 1. The encoded isoform (2) is shorter than isoform 1.
    Source sequence(s)
    AC025162, AK300150, BC001414, DA035117
    Consensus CDS
    CCDS55833.1
    UniProtKB/Swiss-Prot
    P40967
    Related
    ENSP00000450036.1, ENST00000550464.5
    Conserved Domains (2) summary
    PHA03255
    Location:190 → 357
    PHA03255; BDLF3; Provisional
    pfam00801
    Location:149 → 215
    PKD; PKD domain

  2. NM_001200054.1 → NP_001186983.1  melanocyte protein PMEL isoform 1 preproprotein

    See identical proteins and their annotated locations for NP_001186983.1

    Status: REVIEWED

    Description
    Transcript Variant: This variant (1) encodes the longest isoform (1, also known as Pmel17-l).
    Source sequence(s)
    AC025162, BC001414, DA633173, M77348
    Consensus CDS
    CCDS55834.1
    UniProtKB/Swiss-Prot
    P40967
    Related
    ENSP00000402758.2, ENST00000449260.6
    Conserved Domains (2) summary
    PHA03255
    Location:276 → 443
    PHA03255; BDLF3; Provisional
    pfam00801
    Location:235 → 301
    PKD; PKD domain

  3. NM_001320121.1 → NP_001307050.1  melanocyte protein PMEL isoform 4 preproprotein

    Status: REVIEWED

    Description
    Transcript Variant: This variant (4) lacks an alternate in-frame segment in the central coding region compared to variant 1. The encoded isoform (4, also known as Pmel17-ls) is shorter than isoform 1.
    Source sequence(s)
    AC025162
    UniProtKB/Swiss-Prot
    P40967
    Conserved Domains (1) summary
    pfam00801
    Location:235 → 301
    PKD; PKD domain

  4. NM_001320122.1 → NP_001307051.1  melanocyte protein PMEL isoform 5 preproprotein

    Status: REVIEWED

    Description
    Transcript Variant: This variant (5) lacks an alternate in-frame segment in the central coding region and uses an alternate in-frame splice site in the 3' coding region, compared to variant 1. The encoded isoform (5, also known as Pmel17-is) is shorter than isoform 1.
    Source sequence(s)
    AC025162
    UniProtKB/Swiss-Prot
    P40967
    Conserved Domains (1) summary
    pfam00801
    Location:235 → 301
    PKD; PKD domain

  5. NM_001384361.1 → NP_001371290.1  melanocyte protein PMEL isoform 3 preproprotein

    Status: REVIEWED

    Source sequence(s)
    AC025162
    Consensus CDS
    CCDS8897.1
    UniProtKB/Swiss-Prot
    B3KS57, B7Z6D7, P40967, Q12763, Q14448, Q14817, Q16565
    Related
    ENSP00000448828.1, ENST00000548747.6
    Conserved Domains (2) summary
    PHA03255
    Location:276 → 443
    PHA03255; BDLF3; Provisional
    pfam00801
    Location:235 → 301
    PKD; PKD domain

  6. NM_006928.5 → NP_008859.1  melanocyte protein PMEL isoform 3 preproprotein

    See identical proteins and their annotated locations for NP_008859.1

    Status: REVIEWED

    Source sequence(s)
    AC025162
    Consensus CDS
    CCDS8897.1
    UniProtKB/Swiss-Prot
    B3KS57, B7Z6D7, P40967, Q12763, Q14448, Q14817, Q16565
    Related
    ENSP00000447374.1, ENST00000548493.5
    Conserved Domains (2) summary
    PHA03255
    Location:276 → 443
    PHA03255; BDLF3; Provisional
    pfam00801
    Location:235 → 301
    PKD; PKD domain

RefSeqs of Annotated Genomes: GCF_000001405.40-RS_2023_10

The following sections contain reference sequences that belong to a specific genome build. Explain

Reference GRCh38.p14 Primary Assembly

Genomic

  1. NC_000012.12 Reference GRCh38.p14 Primary Assembly

    Range
    55954105..55966709 complement
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)

Alternate T2T-CHM13v2.0

Genomic

  1. NC_060936.1 Alternate T2T-CHM13v2.0

    Range
    55921167..55933772 complement
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

  1. XM_054372923.1 → XP_054228898.1  melanocyte protein PMEL isoform X2

    UniProtKB/Swiss-Prot
    B3KS57, B7Z6D7, P40967, Q12763, Q14448, Q14817, Q16565

  2. XM_054372922.1 → XP_054228897.1  melanocyte protein PMEL isoform X1

Nucleotide Protein
Heading Accession and Version
Protein Accession Links
GenPept Link UniProtKB Link
P40967.2 GenPept UniProtKB/Swiss-Prot:P40967

Gene LinkOut

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