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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

    The following LinkOut resources are supplied by external providers. These providers are responsible for maintaining the links.

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