PMEL_BOVIN
ID PMEL_BOVIN Reviewed; 649 AA.
AC Q06154; A1YKV3;
DT 01-NOV-1997, integrated into UniProtKB/Swiss-Prot.
DT 03-APR-2007, sequence version 2.
DT 25-MAY-2022, entry version 110.
DE RecName: Full=Melanocyte protein PMEL;
DE AltName: Full=Melanocyte protein Pmel 17;
DE AltName: Full=Premelanosome protein;
DE AltName: Full=Retinal pigment epithelial-specific protein;
DE AltName: Full=Silver locus protein homolog;
DE Contains:
DE RecName: Full=M-alpha;
DE Contains:
DE RecName: Full=M-beta;
DE Flags: Precursor;
GN Name=PMEL; Synonyms=PMEL17, RPE1, SILV;
OS Bos taurus (Bovine).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Laurasiatheria; Artiodactyla; Ruminantia; Pecora; Bovidae;
OC Bovinae; Bos.
OX NCBI_TaxID=9913;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC TISSUE=Skin;
RA Kuehn C., Weikard R.;
RT "Investigation on the genetic background of coat color dilution in a
RT Charolais x German Holstein F2 resource population.";
RL Submitted (OCT-2006) to the EMBL/GenBank/DDBJ databases.
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 158-649.
RC TISSUE=Retina;
RX PubMed=1478275; DOI=10.1016/0014-4835(92)90170-w;
RA Kim R.Y., Wistow G.J.;
RT "The cDNA RPE1 and monoclonal antibody HMB-50 define gene products
RT preferentially expressed in retinal pigment epithelium.";
RL Exp. Eye Res. 55:657-662(1992).
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: Retinal pigment epithelium.
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 -!- SIMILARITY: Belongs to the PMEL/NMB family. {ECO:0000305}.
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DR EMBL; EF065525; ABL86707.1; -; mRNA.
DR EMBL; M81193; AAA30419.1; -; mRNA.
DR PIR; A49179; A49179.
DR RefSeq; NP_001073684.2; NM_001080215.2.
DR AlphaFoldDB; Q06154; -.
DR STRING; 9913.ENSBTAP00000005250; -.
DR PaxDb; Q06154; -.
DR GeneID; 281487; -.
DR KEGG; bta:281487; -.
DR CTD; 6490; -.
DR eggNOG; ENOG502QV5K; Eukaryota.
DR InParanoid; Q06154; -.
DR OrthoDB; 393436at2759; -.
DR Proteomes; UP000009136; Unplaced.
DR GO; GO:0005789; C:endoplasmic reticulum membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0005576; C:extracellular region; IEA:UniProtKB-SubCell.
DR GO; GO:0005794; C:Golgi apparatus; IEA:UniProtKB-SubCell.
DR GO; GO:0016021; C:integral component of membrane; IEA:UniProtKB-KW.
DR GO; GO:0042470; C:melanosome; IEA:UniProtKB-SubCell.
DR GO; GO:0005771; C:multivesicular body; IEA:UniProtKB-SubCell.
DR GO; GO:0042438; P:melanin biosynthetic process; IEA:UniProtKB-KW.
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 2: Evidence at transcript level;
KW Cleavage on pair of basic residues; Disulfide bond; Endoplasmic reticulum;
KW Endosome; Glycoprotein; Golgi apparatus; Melanin biosynthesis; Membrane;
KW Reference proteome; Repeat; Secreted; Sialic acid; Signal; Transmembrane;
KW Transmembrane helix.
FT SIGNAL 1..24
FT /evidence="ECO:0000250"
FT CHAIN 25..649
FT /note="Melanocyte protein PMEL"
FT /id="PRO_0000164647"
FT CHAIN 25..453
FT /note="M-alpha"
FT /evidence="ECO:0000250"
FT /id="PRO_0000386646"
FT CHAIN 456..649
FT /note="M-beta"
FT /evidence="ECO:0000250"
FT /id="PRO_0000386647"
FT TOPO_DOM 456..581
FT /note="Lumenal"
FT /evidence="ECO:0000255"
FT TRANSMEM 582..602
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 603..649
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT DOMAIN 217..307
FT /note="PKD"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00151"
FT REPEAT 305..317
FT /note="1"
FT REPEAT 318..330
FT /note="2"
FT REPEAT 331..343
FT /note="3"
FT REPEAT 344..356
FT /note="4"
FT REPEAT 357..369
FT /note="5"
FT REPEAT 370..382
FT /note="6"
FT REPEAT 389..400
FT /note="7"
FT REPEAT 401..413
FT /note="8"
FT REGION 303..327
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 305..413
FT /note="8 X 13 AA approximate tandem repeats, RPT domain"
FT REGION 381..438
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 426
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 554
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CONFLICT 394
FT /note="R -> T (in Ref. 2; AAA30419)"
FT /evidence="ECO:0000305"
FT CONFLICT 477..478
FT /note="QG -> S (in Ref. 2; AAA30419)"
FT /evidence="ECO:0000305"
FT CONFLICT 612
FT /note="A -> E (in Ref. 2; AAA30419)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 649 AA; 69366 MW; F405289FD6D5F07C CRC64;
MDLVLRKYLL HVALMGVLLA VGTTEGPRDR DWLGVSRQLR IKAWNRQLYP EWTESQGPDC
WRGGHISLKV SNDGPTLIGA NASFSIALHF PKSQKVLPDG QVIWANNTII NGSQVWGGQL
VYPQEPDDTC IFPDGEPCPS GPLSQKRCFV YVWKTWDQYW QVLGGPVSGL SIGTDKAMLG
TYNMEVTVYH RRGSQSYVPL AHSSSAFTIT DQVPFSVSVS QLQALDGRNK RFLRKQPLTF
ALQLHDPSGY LAGADLSYTW DFGDSTGTLI SRALTVTHTY LESGPVTAQV VLQAAIPLTS
CGSSPVPGTT DRHVTTAEAP GTTAGQVPTT EVMGTTPGQV PTAEAPGTTV GWVPTTEDVG
TTPEQVATSK VLSTTPVEMP TAKATGRTPE VSTREPSGTT VTQGTTPELV ETTAGEVSTP
EPAGSNTSSF MPTEGTAGSL SPLPDDTATL VLEKRQAPLD CVLYRYGSFS LTLDIVQGIE
SAEILQAVSS SEGDAFELTV SCQGGLPKEA CMDISSPGCQ LPAQRLCQPV PPSPACQLVL
HQVLKGGSGT YCLNVSLADA NSLAMVSTQL VMPGQEAGLR QAPLFVGILL VLTALLLASL
IYRRRLMKQG SAVPLPQLPH GRTQWLRLPW VFRSCPIGES KPLLSGQQV
