PMEL_MOUSE
ID PMEL_MOUSE Reviewed; 626 AA.
AC Q60696;
DT 01-NOV-1997, integrated into UniProtKB/Swiss-Prot.
DT 01-NOV-1996, sequence version 1.
DT 25-MAY-2022, entry version 125.
DE RecName: Full=Melanocyte protein PMEL;
DE AltName: Full=Melanocyte protein Pmel 17;
DE AltName: Full=Premelanosome protein;
DE AltName: Full=Silver locus protein;
DE Contains:
DE RecName: Full=M-alpha;
DE Contains:
DE RecName: Full=M-beta;
DE Flags: Precursor;
GN Name=Pmel; Synonyms=D10H12S53E, Pmel17, Si, Silv;
OS Mus musculus (Mouse).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Mus; Mus.
OX NCBI_TaxID=10090;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA], AND VARIANTS SILVER.
RC STRAIN=C57BL/6J; TISSUE=Skin;
RX PubMed=7870580; DOI=10.1093/nar/23.1.154;
RA Kwon B.S., Halaban R., Ponnazhagan S., Kim K., Chintamaneni C., Bennett D.,
RA Pickard R.T.;
RT "Mouse silver mutation is caused by a single base insertion in the putative
RT cytoplasmic domain of Pmel 17.";
RL Nucleic Acids Res. 23:154-158(1995).
RN [2]
RP PROTEOLYTIC PROCESSING.
RX PubMed=11694580; DOI=10.1091/mbc.12.11.3451;
RA Berson J.F., Harper D.C., Tenza D., Raposo G., Marks M.S.;
RT "Pmel17 initiates premelanosome morphogenesis within multivesicular
RT bodies.";
RL Mol. Biol. Cell 12:3451-3464(2001).
CC -!- FUNCTION: Plays a central role in the biogenesis of melanosomes.
CC Involved in the maturation of melanosomes from stage I to II. The
CC transition from stage I melanosomes to stage II melanosomes involves an
CC elongation of the vesicle, and the appearance within of distinct
CC fibrillar structures (By similarity). {ECO:0000250}.
CC -!- SUBUNIT: Heterooligomer; disulfide-linked heterooligomers of M-alpha
CC and M-beta. Interacts with MLANA. Interacts (via luminal domain) with
CC CD63; this is important for normal sorting of the luminal domain after
CC proteolytic processing (By similarity). {ECO:0000250}.
CC -!- SUBCELLULAR LOCATION: Endoplasmic reticulum membrane {ECO:0000250};
CC Single-pass type I membrane protein {ECO:0000250}. Golgi apparatus
CC {ECO:0000250}. Melanosome {ECO:0000250}. Endosome, multivesicular body
CC {ECO:0000250}. Note=Localizes predominantly to intralumenal vesicles
CC (ILVs) within multivesicular bodies. Associates with ILVs found within
CC the lumen of premelanosomes and melanosomes and particularly in
CC compartments that serve as precursors to the striated stage II
CC premelanosomes (By similarity). {ECO:0000250}.
CC -!- SUBCELLULAR LOCATION: [M-alpha]: Secreted {ECO:0000250}.
CC -!- TISSUE SPECIFICITY: Preferentially expressed in melanocytes.
CC -!- DOMAIN: The RPT domain is essential for the generation of the fibrillar
CC matrix of melanosomes. {ECO:0000250}.
CC -!- DOMAIN: The lumenal domain is necessary for correct processing and
CC trafficking to melanosomes. {ECO:0000250}.
CC -!- PTM: A small amount of P1/P100 (major form) undergoes glycosylation to
CC yield P2/P120 (minor form). P2 is cleaved by a furin-like proprotein
CC convertase (PC) in a pH-dependent manner in a post-Golgi, prelysosomal
CC compartment into two disulfide-linked subunits: a large lumenal
CC subunit, M-alpha/ME20-S, and an integral membrane subunit, M-beta.
CC Despite cleavage, only a small fraction of M-alpha is secreted, whereas
CC most M-alpha and M-beta remain associated with each other
CC intracellularly. M-alpha is further processed to M-alpha N and M-alpha
CC C. M-alpha C further undergoes processing to yield M-alpha C1 and M-
CC alpha C3 (M-alpha C2 in the case of PMEL17-is or PMEL17-ls). Formation
CC of intralumenal fibrils in the melanosomes requires the formation of M-
CC alpha that becomes incorporated into the fibrils. Stage II melanosomes
CC harbor only Golgi-modified Pmel17 fragments that are derived from M-
CC alpha and that bear sialylated O-linked oligosaccharides (By
CC similarity). {ECO:0000250}.
CC -!- PTM: N-glycosylated. O-glycosylated; contains sialic acid (By
CC similarity). {ECO:0000250}.
CC -!- DISEASE: Note=Defects in Silv are the cause of the silver coat color
CC which seems to be due to premature death of pigment cells during the
CC hair cycle.
CC -!- SIMILARITY: Belongs to the PMEL/NMB family. {ECO:0000305}.
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DR EMBL; U14133; AAA69538.1; -; mRNA.
DR PIR; S53871; S53871.
DR AlphaFoldDB; Q60696; -.
DR SMR; Q60696; -.
DR STRING; 10090.ENSMUSP00000051869; -.
DR GlyGen; Q60696; 4 sites.
DR iPTMnet; Q60696; -.
DR PhosphoSitePlus; Q60696; -.
DR PaxDb; Q60696; -.
DR PRIDE; Q60696; -.
DR ProteomicsDB; 289634; -.
DR ABCD; Q60696; 1 sequenced antibody.
DR MGI; MGI:98301; Pmel.
DR eggNOG; ENOG502QV5K; Eukaryota.
DR InParanoid; Q60696; -.
DR PhylomeDB; Q60696; -.
DR ChiTaRS; Pmel; mouse.
DR PRO; PR:Q60696; -.
DR Proteomes; UP000000589; Unplaced.
DR RNAct; Q60696; protein.
DR GO; GO:0005783; C:endoplasmic reticulum; ISO:MGI.
DR GO; GO:0005789; C:endoplasmic reticulum membrane; ISO:MGI.
DR GO; GO:0005576; C:extracellular region; IEA:UniProtKB-SubCell.
DR GO; GO:0005794; C:Golgi apparatus; ISO:MGI.
DR GO; GO:0005887; C:integral component of plasma membrane; IBA:GO_Central.
DR GO; GO:0042470; C:melanosome; IDA:MGI.
DR GO; GO:0032585; C:multivesicular body membrane; ISO:MGI.
DR GO; GO:0042802; F:identical protein binding; ISO:MGI.
DR GO; GO:0042438; P:melanin biosynthetic process; IMP:MGI.
DR GO; GO:0032438; P:melanosome organization; ISO:MGI.
DR GO; GO:0048023; P:positive regulation of melanin biosynthetic process; IMP:CACAO.
DR Gene3D; 2.60.40.10; -; 1.
DR InterPro; IPR013783; Ig-like_fold.
DR InterPro; IPR045219; PKAT.
DR InterPro; IPR022409; PKD/Chitinase_dom.
DR InterPro; IPR000601; PKD_dom.
DR InterPro; IPR035986; PKD_dom_sf.
DR PANTHER; PTHR11861; PTHR11861; 2.
DR Pfam; PF00801; PKD; 1.
DR SMART; SM00089; PKD; 1.
DR SUPFAM; SSF49299; SSF49299; 1.
DR PROSITE; PS50093; PKD; 1.
PE 1: Evidence at protein level;
KW Cleavage on pair of basic residues; Disease variant; Disulfide bond;
KW Endoplasmic reticulum; Endosome; Glycoprotein; Golgi apparatus;
KW Melanin biosynthesis; Membrane; Reference proteome; Repeat; Secreted;
KW Sialic acid; Signal; Transmembrane; Transmembrane helix.
FT SIGNAL 1..24
FT /evidence="ECO:0000255"
FT CHAIN 25..626
FT /note="Melanocyte protein PMEL"
FT /id="PRO_0000024713"
FT CHAIN 25..434
FT /note="M-alpha"
FT /evidence="ECO:0000250"
FT /id="PRO_0000386649"
FT CHAIN 437..626
FT /note="M-beta"
FT /evidence="ECO:0000250"
FT /id="PRO_0000386650"
FT TOPO_DOM 437..562
FT /note="Lumenal"
FT /evidence="ECO:0000255"
FT TRANSMEM 563..583
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 584..626
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT DOMAIN 255..292
FT /note="PKD"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00151"
FT REPEAT 315..327
FT /note="1"
FT REPEAT 328..340
FT /note="2"
FT REPEAT 341..353
FT /note="3"
FT REPEAT 354..366
FT /note="4"
FT REPEAT 367..379
FT /note="5"
FT REPEAT 380..392
FT /note="6"
FT REPEAT 393..411
FT /note="7"
FT REGION 315..411
FT /note="7 X 13 AA approximate tandem repeats, RPT domain"
FT REGION 316..350
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 380..423
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT CARBOHYD 81
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 106
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 111
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 535
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT VARIANT 170
FT /note="S -> L (in silver)"
FT VARIANT 175
FT /note="R -> G (in silver)"
FT VARIANT 373
FT /note="D -> N (in silver)"
FT VARIANT 471
FT /note="F -> S (in silver)"
FT VARIANT 603..626
FT /note="AAPASGLRARGLGENSPLLSGQQV -> SSASLRSSRPRPWRKQPAPQWTAG
FT LIILKAPWISWG (in silver)"
SQ SEQUENCE 626 AA; 65980 MW; 7AB941D2E3FB1044 CRC64;
MVGVQRRSFL PVLVLSALLA VGALEGSRNQ DWLGVPRQLV TKTWNRQLYP EWTEVQGSNC
WRGGQVSLRV INDGPTLVGA NASFSIALHF PGSQKVLPDG QVIWANNTII NGSQVWGGQP
VYPQEPDDAC VFPDGGPCPS GPKPPKRSFV YVWKTWGKYW QVLGGPVSRS SIATRHAKLG
THTMEVTVYH RRGSQSYVPL AHASSTFTIT DQVPFSVSVS QLQALDGETK HFLRNHPLIF
ALQLHDPSGY LAEADLSYTW DFGDGTGTLI SRALDVTHTY LESGSVTAQV VLQAAIPLVS
CGSSPVPGTT DGYMPTAEAP GTTSRQGTTT KVVGTTPGQM PTTQPSGTTV VQMPTTEVTA
TTSEQMLTSA VIDTTLAEVS TTEGTGTTPT RPSGTTVAQA TTTEGPDASP LLPTQSSTGS
ISPLLDDTDT IMLVKRQVPL DCVLYRYGSF SLALDIVQGI ESAEILQAVP FSEGDAFELT
VSCQGGLPKE ACMDISSPGC QPPAQRLCQS VPPSPDCQLV LHQVLKGGSG TYCLNVSLAD
ANSLAVASTQ LVVPGQDGGL GQAPLLVGIL LVLVAVVLAS LILGIDLRSR AQFPKCHMVA
LTAAPASGLR ARGLGENSPL LSGQQV
