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Protein

Melanocyte protein PMEL

Gene

PMEL

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

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.2 Publications

GO - Biological processi

  • developmental pigmentation Source: GO_Central
  • melanin biosynthetic process Source: UniProtKB-KW
  • melanosome organization Source: UniProtKB
Complete GO annotation...

Keywords - Biological processi

Melanin biosynthesis

Keywords - Ligandi

Sialic acid

Names & Taxonomyi

Protein namesi
Recommended name:
Melanocyte protein PMEL
Alternative name(s):
ME20-M
Short name:
ME20M
Melanocyte protein Pmel 17
Melanocytes lineage-specific antigen GP100
Melanoma-associated ME20 antigen
P1
P100
Premelanosome protein
Silver locus protein homolog
Cleaved into the following 2 chains:
Alternative name(s):
95 kDa melanocyte-specific secreted glycoprotein
P26
Secreted melanoma-associated ME20 antigen
Short name:
ME20-S
Short name:
ME20S
Gene namesi
Name:PMEL
Synonyms:D12S53E, PMEL17, SILV
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 12

Organism-specific databases

HGNCiHGNC:10880. PMEL.

Subcellular locationi

Topology

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Topological domaini470 – 595LumenalSequence analysisAdd BLAST126
Transmembranei596 – 616HelicalSequence analysisAdd BLAST21
Topological domaini617 – 661CytoplasmicSequence analysisAdd BLAST45

GO - Cellular componenti

  • endoplasmic reticulum membrane Source: UniProtKB
  • extracellular region Source: UniProtKB-SubCell
  • Golgi apparatus Source: UniProtKB
  • integral component of plasma membrane Source: GO_Central
  • melanosome Source: UniProtKB
  • multivesicular body membrane Source: UniProtKB
  • plasma membrane Source: ProtInc
Complete GO annotation...

Keywords - Cellular componenti

Endoplasmic reticulum, Endosome, Golgi apparatus, Membrane, Secreted

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi468 – 469KR → QQ: Loss of proteolytic cleavage. 1 Publication2

Organism-specific databases

DisGeNETi6490.
OpenTargetsiENSG00000185664.
PharmGKBiPA35781.

Polymorphism and mutation databases

BioMutaiPMEL.
DMDMi2507099.

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Signal peptidei1 – 241 PublicationAdd BLAST24
ChainiPRO_000002471225 – 661Melanocyte protein PMELAdd BLAST637
ChainiPRO_000029226325 – 467M-alphaAdd BLAST443
ChainiPRO_0000386648470 – 661M-betaAdd BLAST192

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Glycosylationi81N-linked (GlcNAc...)Sequence analysis1
Glycosylationi106N-linked (GlcNAc...)Sequence analysis1
Glycosylationi111N-linked (GlcNAc...)Sequence analysis1
Glycosylationi321N-linked (GlcNAc...)Sequence analysis1
Glycosylationi568N-linked (GlcNAc...)Sequence analysis1

Post-translational modificationi

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.5 Publications
N-glycosylated. O-glycosylated; contains sialic acid.

Keywords - PTMi

Cleavage on pair of basic residues, Disulfide bond, Glycoprotein

Proteomic databases

PaxDbiP40967.
PeptideAtlasiP40967.
PRIDEiP40967.

PTM databases

iPTMnetiP40967.
PhosphoSitePlusiP40967.

Expressioni

Tissue specificityi

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.

Gene expression databases

BgeeiENSG00000185664.
CleanExiHS_SILV.
ExpressionAtlasiP40967. baseline and differential.
GenevisibleiP40967. HS.

Organism-specific databases

HPAiHPA031649.

Interactioni

Subunit structurei

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.3 Publications

Protein-protein interaction databases

BioGridi112381. 49 interactors.
DIPiDIP-48937N.
MINTiMINT-4723252.
STRINGi9606.ENSP00000402758.

Structurei

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
1TVBX-ray1.80C/F209-217[»]
1TVHX-ray1.80C/F209-217[»]
3CC5X-ray1.91C/F25-33[»]
4IS6X-ray2.50C44-59[»]
5EU3X-ray1.97C280-288[»]
5EU4X-ray2.12C/F280-288[»]
5EU6X-ray2.02C280-287[»]
ProteinModelPortaliP40967.
SMRiP40967.
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiP40967.

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini255 – 292PKDPROSITE-ProRule annotationAdd BLAST38
Repeati315 – 3271Add BLAST13
Repeati328 – 3402Add BLAST13
Repeati341 – 3533Add BLAST13
Repeati354 – 3664Add BLAST13
Repeati367 – 3795Add BLAST13
Repeati380 – 3926Add BLAST13
Repeati393 – 4057Add BLAST13
Repeati406 – 4188Add BLAST13
Repeati419 – 4319Add BLAST13
Repeati432 – 44410Add BLAST13

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni315 – 44410 X 13 AA approximate tandem repeats, RPT domainAdd BLAST130

Domaini

The RPT domain is essential for the generation of the fibrillar matrix of melanosomes.1 Publication
The lumenal domain is necessary for correct processing and trafficking to melanosomes.1 Publication

Sequence similaritiesi

Belongs to the PMEL/NMB family.Curated
Contains 1 PKD domain.PROSITE-ProRule annotation

Keywords - Domaini

Repeat, Signal, Transmembrane, Transmembrane helix

Phylogenomic databases

eggNOGiENOG410IHN4. Eukaryota.
ENOG410Z44K. LUCA.
GeneTreeiENSGT00530000063573.
HOVERGENiHBG099694.
InParanoidiP40967.
KOiK17304.
OMAiIYRRRLM.
OrthoDBiEOG091G05UD.
PhylomeDBiP40967.
TreeFamiTF334865.

Family and domain databases

Gene3Di2.60.40.670. 1 hit.
InterProiIPR022409. PKD/Chitinase_dom.
IPR000601. PKD_dom.
[Graphical view]
PfamiPF00801. PKD. 1 hit.
[Graphical view]
SMARTiSM00089. PKD. 1 hit.
[Graphical view]
SUPFAMiSSF49299. SSF49299. 1 hit.
PROSITEiPS50093. PKD. 1 hit.
[Graphical view]

Sequences (5)i

Sequence statusi: Complete.

Sequence processingi: The displayed sequence is further processed into a mature form.

This entry describes 5 isoformsi produced by alternative splicing. AlignAdd to basket

Isoform 1 (identifier: P40967-1) [UniParc]FASTAAdd to basket
Also known as: Intermediate form, Pmel17-i

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

« Hide

        10         20         30         40         50
MDLVLKRCLL HLAVIGALLA VGATKVPRNQ DWLGVSRQLR TKAWNRQLYP
60 70 80 90 100
EWTEAQRLDC WRGGQVSLKV SNDGPTLIGA NASFSIALNF PGSQKVLPDG
110 120 130 140 150
QVIWVNNTII NGSQVWGGQP VYPQETDDAC IFPDGGPCPS GSWSQKRSFV
160 170 180 190 200
YVWKTWGQYW QVLGGPVSGL SIGTGRAMLG THTMEVTVYH RRGSRSYVPL
210 220 230 240 250
AHSSSAFTIT DQVPFSVSVS QLRALDGGNK HFLRNQPLTF ALQLHDPSGY
260 270 280 290 300
LAEADLSYTW DFGDSSGTLI SRALVVTHTY LEPGPVTAQV VLQAAIPLTS
310 320 330 340 350
CGSSPVPGTT DGHRPTAEAP NTTAGQVPTT EVVGTTPGQA PTAEPSGTTS
360 370 380 390 400
VQVPTTEVIS TAPVQMPTAE STGMTPEKVP VSEVMGTTLA EMSTPEATGM
410 420 430 440 450
TPAEVSIVVL SGTTAAQVTT TEWVETTARE LPIPEPEGPD ASSIMSTESI
460 470 480 490 500
TGSLGPLLDG TATLRLVKRQ VPLDCVLYRY GSFSVTLDIV QGIESAEILQ
510 520 530 540 550
AVPSGEGDAF ELTVSCQGGL PKEACMEISS PGCQPPAQRL CQPVLPSPAC
560 570 580 590 600
QLVLHQILKG GSGTYCLNVS LADTNSLAVV STQLIMPGQE AGLGQVPLIV
610 620 630 640 650
GILLVLMAVV LASLIYRRRL MKQDFSVPQL PHSSSHWLRL PRIFCSCPIG
660
ENSPLLSGQQ V
Length:661
Mass (Da):70,255
Last modified:November 1, 1997 - v2
Checksum:i8A904FAB16715653
GO
Isoform 2 (identifier: P40967-2) [UniParc]FASTAAdd to basket
Also known as: Long form, Pmel17-l

The sequence of this isoform differs from the canonical sequence as follows:
     587-587: P → PVPGILLT

Show »
Length:668
Mass (Da):70,949
Checksum:iCF204FFB7E026791
GO
Isoform 3 (identifier: P40967-3) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     26-111: Missing.

Show »
Length:575
Mass (Da):60,581
Checksum:i2D84400CD1A8FE4E
GO
Isoform 4 (identifier: P40967-4) [UniParc]FASTAAdd to basket
Also known as: Short form, Pmel17-ls

The sequence of this isoform differs from the canonical sequence as follows:
     373-414: Missing.

Show »
Length:619
Mass (Da):66,035
Checksum:iCAE0E8B0EF10550B
GO
Isoform 5 (identifier: P40967-5) [UniParc]FASTAAdd to basket
Also known as: Short form, Pmel17-is

The sequence of this isoform differs from the canonical sequence as follows:
     373-414: Missing.
     587-587: P → PVPGILLT

Show »
Length:626
Mass (Da):66,729
Checksum:i8ECA4B3E15B0CD51
GO

Sequence cautioni

The sequence AAA35930 differs from that shown. Reason: Frameshift at position 642.Curated
The sequence AAA35930 differs from that shown. Reason: Erroneous initiation. Translation N-terminally extended.Curated

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti162V → F no nucleotide entry (PubMed:8022805).Curated1
Sequence conflicti274L → P in AAA60121 (PubMed:1924386).Curated1
Sequence conflicti274L → P in AAB19181 (PubMed:8739560).Curated1
Sequence conflicti373G → S in BAH13223 (PubMed:14702039).Curated1
Sequence conflicti592G → GG AA sequence (PubMed:8179825).Curated1
Sequence conflicti597P → R in AAA60121 (PubMed:1924386).Curated1

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_050606320P → H.Corresponds to variant rs2071024dbSNPEnsembl.1
Natural variantiVAR_050607370E → D.Corresponds to variant rs17118154dbSNPEnsembl.1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_03826626 – 111Missing in isoform 3. 1 PublicationAdd BLAST86
Alternative sequenceiVSP_038267373 – 414Missing in isoform 4 and isoform 5. CuratedAdd BLAST42
Alternative sequenceiVSP_038268587P → PVPGILLT in isoform 2 and isoform 5. 1 Publication1

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
M77348 mRNA. Translation: AAA60121.1.
U01874 mRNA. Translation: AAA18479.1.
S73003 mRNA. Translation: AAC60634.1.
U31799
, U31808, U31807, U31797, U31798 Genomic DNA. Translation: AAB00386.1.
U20093, U19491 Genomic DNA. Translation: AAB19181.1.
M32295 mRNA. Translation: AAA35930.1. Sequence problems.
BT007202 mRNA. Translation: AAP35866.1.
AK092881 mRNA. Translation: BAG52619.1.
AK300150 mRNA. Translation: BAH13223.1.
AC025162 Genomic DNA. No translation available.
CH471054 Genomic DNA. Translation: EAW96853.1.
BC001414 mRNA. Translation: AAH01414.1.
CCDSiCCDS55833.1. [P40967-3]
CCDS55834.1. [P40967-2]
CCDS8897.1. [P40967-1]
PIRiA41234.
I38400.
RefSeqiNP_001186982.1. NM_001200053.1. [P40967-3]
NP_001186983.1. NM_001200054.1. [P40967-2]
NP_001307050.1. NM_001320121.1. [P40967-5]
NP_001307051.1. NM_001320122.1. [P40967-4]
NP_008859.1. NM_006928.4. [P40967-1]
XP_006719632.1. XM_006719569.1. [P40967-1]
XP_011536987.1. XM_011538685.1. [P40967-2]
UniGeneiHs.95972.

Genome annotation databases

EnsembliENST00000449260; ENSP00000402758; ENSG00000185664. [P40967-2]
ENST00000548493; ENSP00000447374; ENSG00000185664. [P40967-1]
ENST00000548747; ENSP00000448828; ENSG00000185664. [P40967-1]
ENST00000550464; ENSP00000450036; ENSG00000185664. [P40967-3]
ENST00000552882; ENSP00000449690; ENSG00000185664. [P40967-1]
GeneIDi6490.
KEGGihsa:6490.
UCSCiuc001sip.4. human. [P40967-1]

Keywords - Coding sequence diversityi

Alternative splicing, Polymorphism

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
M77348 mRNA. Translation: AAA60121.1.
U01874 mRNA. Translation: AAA18479.1.
S73003 mRNA. Translation: AAC60634.1.
U31799
, U31808, U31807, U31797, U31798 Genomic DNA. Translation: AAB00386.1.
U20093, U19491 Genomic DNA. Translation: AAB19181.1.
M32295 mRNA. Translation: AAA35930.1. Sequence problems.
BT007202 mRNA. Translation: AAP35866.1.
AK092881 mRNA. Translation: BAG52619.1.
AK300150 mRNA. Translation: BAH13223.1.
AC025162 Genomic DNA. No translation available.
CH471054 Genomic DNA. Translation: EAW96853.1.
BC001414 mRNA. Translation: AAH01414.1.
CCDSiCCDS55833.1. [P40967-3]
CCDS55834.1. [P40967-2]
CCDS8897.1. [P40967-1]
PIRiA41234.
I38400.
RefSeqiNP_001186982.1. NM_001200053.1. [P40967-3]
NP_001186983.1. NM_001200054.1. [P40967-2]
NP_001307050.1. NM_001320121.1. [P40967-5]
NP_001307051.1. NM_001320122.1. [P40967-4]
NP_008859.1. NM_006928.4. [P40967-1]
XP_006719632.1. XM_006719569.1. [P40967-1]
XP_011536987.1. XM_011538685.1. [P40967-2]
UniGeneiHs.95972.

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
1TVBX-ray1.80C/F209-217[»]
1TVHX-ray1.80C/F209-217[»]
3CC5X-ray1.91C/F25-33[»]
4IS6X-ray2.50C44-59[»]
5EU3X-ray1.97C280-288[»]
5EU4X-ray2.12C/F280-288[»]
5EU6X-ray2.02C280-287[»]
ProteinModelPortaliP40967.
SMRiP40967.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi112381. 49 interactors.
DIPiDIP-48937N.
MINTiMINT-4723252.
STRINGi9606.ENSP00000402758.

PTM databases

iPTMnetiP40967.
PhosphoSitePlusiP40967.

Polymorphism and mutation databases

BioMutaiPMEL.
DMDMi2507099.

Proteomic databases

PaxDbiP40967.
PeptideAtlasiP40967.
PRIDEiP40967.

Protocols and materials databases

DNASUi6490.
Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000449260; ENSP00000402758; ENSG00000185664. [P40967-2]
ENST00000548493; ENSP00000447374; ENSG00000185664. [P40967-1]
ENST00000548747; ENSP00000448828; ENSG00000185664. [P40967-1]
ENST00000550464; ENSP00000450036; ENSG00000185664. [P40967-3]
ENST00000552882; ENSP00000449690; ENSG00000185664. [P40967-1]
GeneIDi6490.
KEGGihsa:6490.
UCSCiuc001sip.4. human. [P40967-1]

Organism-specific databases

CTDi6490.
DisGeNETi6490.
GeneCardsiPMEL.
HGNCiHGNC:10880. PMEL.
HPAiHPA031649.
MIMi155550. gene.
neXtProtiNX_P40967.
OpenTargetsiENSG00000185664.
PharmGKBiPA35781.
GenAtlasiSearch...

Phylogenomic databases

eggNOGiENOG410IHN4. Eukaryota.
ENOG410Z44K. LUCA.
GeneTreeiENSGT00530000063573.
HOVERGENiHBG099694.
InParanoidiP40967.
KOiK17304.
OMAiIYRRRLM.
OrthoDBiEOG091G05UD.
PhylomeDBiP40967.
TreeFamiTF334865.

Miscellaneous databases

ChiTaRSiPMEL. human.
EvolutionaryTraceiP40967.
GeneWikiiPMEL_(gene).
GenomeRNAii6490.
PROiP40967.
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000185664.
CleanExiHS_SILV.
ExpressionAtlasiP40967. baseline and differential.
GenevisibleiP40967. HS.

Family and domain databases

Gene3Di2.60.40.670. 1 hit.
InterProiIPR022409. PKD/Chitinase_dom.
IPR000601. PKD_dom.
[Graphical view]
PfamiPF00801. PKD. 1 hit.
[Graphical view]
SMARTiSM00089. PKD. 1 hit.
[Graphical view]
SUPFAMiSSF49299. SSF49299. 1 hit.
PROSITEiPS50093. PKD. 1 hit.
[Graphical view]
ProtoNetiSearch...

Entry informationi

Entry nameiPMEL_HUMAN
AccessioniPrimary (citable) accession number: P40967
Secondary accession number(s): B3KS57
, B7Z6D7, Q12763, Q14448, Q14817, Q16565
Entry historyi
Integrated into UniProtKB/Swiss-Prot: February 1, 1995
Last sequence update: November 1, 1997
Last modified: November 2, 2016
This is version 149 of the entry and version 2 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

Miscellaneousi

Keywords - Technical termi

3D-structure, Complete proteome, Direct protein sequencing, Reference proteome

Documents

  1. Human chromosome 12
    Human chromosome 12: entries, gene names and cross-references to MIM
  2. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  3. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  4. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  5. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  6. SIMILARITY comments
    Index of protein domains and families

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.