PMEL

Protein identityUniProt · HPA

UniProt accession

P40967

Gene

PMEL

Ensembl

ENSG00000185664

Chromosome

12

Canonical length

661 aa

Protein class

FDA approved drug targets, Predicted intracellular proteins, Predicted membrane proteins

Subcellular location

Endoplasmic reticulum,Golgi apparatus

Secretome location

Intracellular and membrane

Quaternary structure

Homodimer

OverviewNCBI 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]

Canonical amino-acid sequenceUniProt

661 residues, UniProt reviewed canonical sequence.

>P40967|PMEL
     1  MDLVLKRCLL HLAVIGALLA VGATKVPRNQ DWLGVSRQLR TKAWNRQLYP EWTEAQRLDC
    61  WRGGQVSLKV SNDGPTLIGA NASFSIALNF PGSQKVLPDG QVIWVNNTII NGSQVWGGQP
   121  VYPQETDDAC IFPDGGPCPS GSWSQKRSFV YVWKTWGQYW QVLGGPVSGL SIGTGRAMLG
   181  THTMEVTVYH RRGSRSYVPL AHSSSAFTIT DQVPFSVSVS QLRALDGGNK HFLRNQPLTF
   241  ALQLHDPSGY LAEADLSYTW DFGDSSGTLI SRALVVTHTY LEPGPVTAQV VLQAAIPLTS
   301  CGSSPVPGTT DGHRPTAEAP NTTAGQVPTT EVVGTTPGQA PTAEPSGTTS VQVPTTEVIS
   361  TAPVQMPTAE STGMTPEKVP VSEVMGTTLA EMSTPEATGM TPAEVSIVVL SGTTAAQVTT
   421  TEWVETTARE LPIPEPEGPD ASSIMSTESI TGSLGPLLDG TATLRLVKRQ VPLDCVLYRY
   481  GSFSVTLDIV QGIESAEILQ AVPSGEGDAF ELTVSCQGGL PKEACMEISS PGCQPPAQRL
   541  CQPVLPSPAC QLVLHQILKG GSGTYCLNVS LADTNSLAVV STQLIMPGQE AGLGQVPLIV
   601  GILLVLMAVV LASLIYRRRL MKQDFSVPQL PHSSSHWLRL PRIFCSCPIG ENSPLLSGQQ
   661  V

LocalizationUniProt · AlphaFold · HPA

Whether an antibody against PMEL can act on the native protein depends on physical access: surface and secreted proteins are reachable by circulating antibodies, intracellular proteins usually are not.

Antibody reachability

Secreted

Secreted

Yes

Transmembrane segments

1

Mean surface accessibility (rSASA)

0.46

Highest tissue expression

109 nTPM

Expression across tissuesHPA

DiseaseUniProt · ClinVar · IEDB · PubMed

Four sources answering four different questions about PMEL.

Disease | ImmuneIEDB

Conditions an epitope on PMEL was assayed in.

• melanoma T cell
• skin melanoma B and T cell
• vitiligo B and T cell
• alopecia areata T cell
• Vogt-Koyanagi-Harada disease T cell

Disease | AutoantibodyPubMed

Conditions in which antibodies against PMEL are reported. Each links to that disease's full target list.

• Vitiligo 4

ReferencesPubMed · IEDB

Publications for PMEL from three distinct lines of evidence, kept separate because they answer different questions: whether antibodies are directed at the protein, whether a B-cell epitope has been mapped on it, and whether a T-cell epitope has. Each is labelled with its source.

Sources: PubMed — antigen-level antibody evidence from a custom retrieval. Records matching a controlled set of autoantibody terms (the MeSH descriptors Autoantibodies and Autoantigens, with title and abstract term variants) were obtained through NCBI E-utilities, and their titles and abstracts parsed for constructions that direct an antibody at a named protein rather than for co-occurrence. Captured names were resolved against UniProt nomenclature and each antigen adjudicated individually against the source text. IEDB — curated epitope assays from the Immune Epitope Database (Vita et al., Nucleic Acids Research 2019). Bibliographic records from PubMed and MeSH, U.S. National Library of Medicine; citation metrics from NIH iCite (Hutchins et al., PLoS Biology 2016). Titles link to PubMed; abstracts are not reproduced here. The NLM does not endorse this analysis.

Genetic constraint and essentialitygnomAD · DepMap

Does the body need this protein intact? Low LOEUF or a strong DepMap dependency means loss or blockade of the protein is likely to be felt.

gnomAD LOEUF (loss-of-function intolerance)

1.29

gnomAD pLI

0

gnomAD missense Z

0.89

DepMap mean gene effect

-0.1

DepMap dependency class

selective

Cancer expressionTCGA

Across TCGA tumor cohorts, this protein is over-expressed in roughly 3% of surveyed tumor types (aggregate summary; per-cohort expression, alteration, and survival load in the interactive view).

OntologyGO

Biological processes

• melanin biosynthetic process
• melanosome organization
• positive regulation of melanin biosynthetic process

Molecular functions

• identical protein binding

Cellular components

• cis-Golgi network membrane
• endoplasmic reticulum
• endoplasmic reticulum membrane
• extracellular exosome
• Golgi apparatus
• melanosome
• melanosome membrane
• multivesicular body membrane
• multivesicular body, internal vesicle
• plasma membrane

Protein domainsUniProt · Pfam · InterPro

• PKD domain
• Immunoglobulin-like fold
• PKD/Chitinase domain
• PKD domain superfamily
• PKD- and KLD-Associated Transmembrane
• PKAT, KLD domain
• PMEL/NMB, N-terminal domain
• PKD domain
• PKAT, KLD domain
• PMEL/NMB N-terminal domain

KeywordsUniProt

• Cleavage on pair of basic residues
• Disulfide bond
• Endoplasmic reticulum
• Endosome
• Glycoprotein
• Golgi apparatus
• Melanin biosynthesis
• Membrane
• Repeat
• Secreted
• Sialic acid
• Signal
• Transmembrane
• Transmembrane helix

InteractionsUniProt · HPA

Protein binding partners of PMEL in the human serome: UniProt-annotated complex subunits plus reported interactors. Each links to its own Seroatlas record.

• APOE
• MLANA
• CD63