PMEL_HUMAN
ID PMEL_HUMAN Reviewed; 661 AA.
AC P40967; B3KS57; B7Z6D7; Q12763; Q14448; Q14817; Q16565;
DT 01-FEB-1995, integrated into UniProtKB/Swiss-Prot.
DT 01-NOV-1997, sequence version 2.
DT 03-AUG-2022, entry version 188.
DE RecName: Full=Melanocyte protein PMEL;
DE AltName: Full=ME20-M;
DE Short=ME20M;
DE AltName: Full=Melanocyte protein Pmel 17;
DE AltName: Full=Melanocytes lineage-specific antigen GP100;
DE AltName: Full=Melanoma-associated ME20 antigen;
DE AltName: Full=P1;
DE AltName: Full=P100;
DE AltName: Full=Premelanosome protein;
DE AltName: Full=Silver locus protein homolog;
DE Contains:
DE RecName: Full=M-alpha;
DE AltName: Full=95 kDa melanocyte-specific secreted glycoprotein;
DE AltName: Full=P26;
DE AltName: Full=Secreted melanoma-associated ME20 antigen;
DE Short=ME20-S;
DE Short=ME20S;
DE Contains:
DE RecName: Full=M-beta;
DE Flags: Precursor;
GN Name=PMEL; Synonyms=D12S53E, PMEL17, SILV;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2).
RX PubMed=1924386; DOI=10.1073/pnas.88.20.9228;
RA Kwon B.S., Chintamaneni C., Kozak C.A., Copeland N.G., Gilbert D.J.,
RA Jenkins N.A., Barton D., Francke U., Kobayashi Y., Kim K.-K.;
RT "A melanocyte-specific gene, Pmel 17, maps near the silver coat color locus
RT on mouse chromosome 10 and is in a syntenic region on human chromosome
RT 12.";
RL Proc. Natl. Acad. Sci. U.S.A. 88:9228-9232(1991).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), AND PROTEIN SEQUENCE OF 25-53.
RX PubMed=8179825; DOI=10.1089/dna.1994.13.87;
RA Maresh G.A., Marken J.S., Neubauer M., Aruffo A., Hellstroem I.,
RA Hellstroem K.E., Marquardt H.;
RT "Cloning and expression of the gene for the melanoma-associated ME20
RT antigen.";
RL DNA Cell Biol. 13:87-95(1994).
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
RX PubMed=7519602; DOI=10.1016/s0021-9258(17)32136-1;
RA Adema G.J., de Boer A.J., Vogel A.M., Loenen W.A., Figdor C.G.;
RT "Molecular characterization of the melanocyte lineage-specific antigen
RT gp100.";
RL J. Biol. Chem. 269:20126-20133(1994).
RN [4]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
RX PubMed=8022805; DOI=10.1073/pnas.91.14.6458;
RA Kawakami Y., Eliyahu S., Delgado C.H., Robbins P.F., Sakaguchi K.,
RA Appella E., Yannelli J.R., Adema G.J., Miki T., Rosenberg S.A.;
RT "Identification of a human melanoma antigen recognized by tumor-
RT infiltrating lymphocytes associated with in vivo tumor rejection.";
RL Proc. Natl. Acad. Sci. U.S.A. 91:6458-6462(1994).
RN [5]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND ALTERNATIVE SPLICING (ISOFORM 1).
RX PubMed=8592076; DOI=10.1111/1523-1747.ep12326976;
RA Bailin T., Lee S.-T., Spritz R.A.;
RT "Genomic organization and sequence of D12S53E (Pmel 17), the human
RT homologue of the mouse silver (si) locus.";
RL J. Invest. Dermatol. 106:24-27(1996).
RN [6]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND ALTERNATIVE SPLICING (ISOFORM 1).
RX PubMed=8739560; DOI=10.1111/j.1600-0749.1996.tb00085.x;
RA Kim K.K., Youn B.S., Heng H.H.Q., Shi X.-M., Tsui L.-C., Lee Z.H.,
RA Pickard R.T., Kwon B.S.;
RT "Genomic organization and FISH mapping of human Pmel 17, the putative
RT silver locus.";
RL Pigment Cell Res. 9:42-48(1996).
RN [7]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
RA Vogel A.;
RT "Sequence of a melanocyte specific secreted glycoprotein.";
RL Submitted (NOV-1990) to the EMBL/GenBank/DDBJ databases.
RN [8]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RA Kalnine N., Chen X., Rolfs A., Halleck A., Hines L., Eisenstein S.,
RA Koundinya M., Raphael J., Moreira D., Kelley T., LaBaer J., Lin Y.,
RA Phelan M., Farmer A.;
RT "Cloning of human full-length CDSs in BD Creator(TM) system donor vector.";
RL Submitted (MAY-2003) to the EMBL/GenBank/DDBJ databases.
RN [9]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 3).
RC TISSUE=Placenta, and Spleen;
RX PubMed=14702039; DOI=10.1038/ng1285;
RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R.,
RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H.,
RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.,
RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K.,
RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H.,
RA Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M.,
RA Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K.,
RA Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T.,
RA Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M.,
RA Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S.,
RA Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H.,
RA Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K.,
RA Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N.,
RA Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S.,
RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O.,
RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H.,
RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B.,
RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y.,
RA Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K.,
RA Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T.,
RA Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T.,
RA Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y.,
RA Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H.,
RA Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y.,
RA Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H.,
RA Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O.,
RA Isogai T., Sugano S.;
RT "Complete sequencing and characterization of 21,243 full-length human
RT cDNAs.";
RL Nat. Genet. 36:40-45(2004).
RN [10]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=16541075; DOI=10.1038/nature04569;
RA Scherer S.E., Muzny D.M., Buhay C.J., Chen R., Cree A., Ding Y.,
RA Dugan-Rocha S., Gill R., Gunaratne P., Harris R.A., Hawes A.C.,
RA Hernandez J., Hodgson A.V., Hume J., Jackson A., Khan Z.M., Kovar-Smith C.,
RA Lewis L.R., Lozado R.J., Metzker M.L., Milosavljevic A., Miner G.R.,
RA Montgomery K.T., Morgan M.B., Nazareth L.V., Scott G., Sodergren E.,
RA Song X.-Z., Steffen D., Lovering R.C., Wheeler D.A., Worley K.C., Yuan Y.,
RA Zhang Z., Adams C.Q., Ansari-Lari M.A., Ayele M., Brown M.J., Chen G.,
RA Chen Z., Clerc-Blankenburg K.P., Davis C., Delgado O., Dinh H.H.,
RA Draper H., Gonzalez-Garay M.L., Havlak P., Jackson L.R., Jacob L.S.,
RA Kelly S.H., Li L., Li Z., Liu J., Liu W., Lu J., Maheshwari M.,
RA Nguyen B.-V., Okwuonu G.O., Pasternak S., Perez L.M., Plopper F.J.H.,
RA Santibanez J., Shen H., Tabor P.E., Verduzco D., Waldron L., Wang Q.,
RA Williams G.A., Zhang J., Zhou J., Allen C.C., Amin A.G., Anyalebechi V.,
RA Bailey M., Barbaria J.A., Bimage K.E., Bryant N.P., Burch P.E.,
RA Burkett C.E., Burrell K.L., Calderon E., Cardenas V., Carter K., Casias K.,
RA Cavazos I., Cavazos S.R., Ceasar H., Chacko J., Chan S.N., Chavez D.,
RA Christopoulos C., Chu J., Cockrell R., Cox C.D., Dang M., Dathorne S.R.,
RA David R., Davis C.M., Davy-Carroll L., Deshazo D.R., Donlin J.E.,
RA D'Souza L., Eaves K.A., Egan A., Emery-Cohen A.J., Escotto M., Flagg N.,
RA Forbes L.D., Gabisi A.M., Garza M., Hamilton C., Henderson N.,
RA Hernandez O., Hines S., Hogues M.E., Huang M., Idlebird D.G., Johnson R.,
RA Jolivet A., Jones S., Kagan R., King L.M., Leal B., Lebow H., Lee S.,
RA LeVan J.M., Lewis L.C., London P., Lorensuhewa L.M., Loulseged H.,
RA Lovett D.A., Lucier A., Lucier R.L., Ma J., Madu R.C., Mapua P.,
RA Martindale A.D., Martinez E., Massey E., Mawhiney S., Meador M.G.,
RA Mendez S., Mercado C., Mercado I.C., Merritt C.E., Miner Z.L., Minja E.,
RA Mitchell T., Mohabbat F., Mohabbat K., Montgomery B., Moore N., Morris S.,
RA Munidasa M., Ngo R.N., Nguyen N.B., Nickerson E., Nwaokelemeh O.O.,
RA Nwokenkwo S., Obregon M., Oguh M., Oragunye N., Oviedo R.J., Parish B.J.,
RA Parker D.N., Parrish J., Parks K.L., Paul H.A., Payton B.A., Perez A.,
RA Perrin W., Pickens A., Primus E.L., Pu L.-L., Puazo M., Quiles M.M.,
RA Quiroz J.B., Rabata D., Reeves K., Ruiz S.J., Shao H., Sisson I.,
RA Sonaike T., Sorelle R.P., Sutton A.E., Svatek A.F., Svetz L.A.,
RA Tamerisa K.S., Taylor T.R., Teague B., Thomas N., Thorn R.D., Trejos Z.Y.,
RA Trevino B.K., Ukegbu O.N., Urban J.B., Vasquez L.I., Vera V.A.,
RA Villasana D.M., Wang L., Ward-Moore S., Warren J.T., Wei X., White F.,
RA Williamson A.L., Wleczyk R., Wooden H.S., Wooden S.H., Yen J., Yoon L.,
RA Yoon V., Zorrilla S.E., Nelson D., Kucherlapati R., Weinstock G.,
RA Gibbs R.A.;
RT "The finished DNA sequence of human chromosome 12.";
RL Nature 440:346-351(2006).
RN [11]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M.,
RA Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J.,
RA Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S.,
RA Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H.,
RA Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K.,
RA Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D.,
RA Hunkapiller M.W., Myers E.W., Venter J.C.;
RL Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases.
RN [12]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC TISSUE=Placenta;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [13]
RP ALTERNATIVE SPLICING (ISOFORMS 4 AND 5).
RX PubMed=14632201; DOI=10.1046/j.1523-1747.2003.12474.x;
RA Nichols S.E., Harper D.C., Berson J.F., Marks M.S.;
RT "A novel splice variant of Pmel17 expressed by human melanocytes and
RT melanoma cells lacking some of the internal repeats.";
RL J. Invest. Dermatol. 121:821-830(2003).
RN [14]
RP SUBCELLULAR LOCATION, PROTEOLYTIC PROCESSING, SUBUNIT, FUNCTION, AND
RP GLYCOSYLATION.
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).
RN [15]
RP PROTEOLYTIC PROCESSING, AND MUTAGENESIS OF 468-LYS--ARG-469.
RX PubMed=12732614; DOI=10.1083/jcb.200302072;
RA Berson J.F., Theos A.C., Harper D.C., Tenza D., Raposo G., Marks M.S.;
RT "Proprotein convertase cleavage liberates a fibrillogenic fragment of a
RT resident glycoprotein to initiate melanosome biogenesis.";
RL J. Cell Biol. 161:521-533(2003).
RN [16]
RP SUBCELLULAR LOCATION [LARGE SCALE ANALYSIS].
RC TISSUE=Melanoma;
RX PubMed=12643545; DOI=10.1021/pr025562r;
RA Basrur V., Yang F., Kushimoto T., Higashimoto Y., Yasumoto K., Valencia J.,
RA Muller J., Vieira W.D., Watabe H., Shabanowitz J., Hearing V.J., Hunt D.F.,
RA Appella E.;
RT "Proteomic analysis of early melanosomes: identification of novel
RT melanosomal proteins.";
RL J. Proteome Res. 2:69-79(2003).
RN [17]
RP PROTEOLYTIC PROCESSING, AND GLYCOSYLATION.
RX PubMed=15096515; DOI=10.1074/jbc.m401269200;
RA Yasumoto K.-I., Watabe H., Valencia J.C., Kushimoto T., Kobayashi T.,
RA Appella E., Hearing V.J.;
RT "Epitope mapping of the melanosomal matrix protein gp100 (PMEL17): rapid
RT processing in the endoplasmic reticulum and glycosylation in the early
RT Golgi compartment.";
RL J. Biol. Chem. 279:28330-28338(2004).
RN [18]
RP PROTEOLYTIC PROCESSING, SUBCELLULAR LOCATION, AND INTERACTION WITH MLANA.
RX PubMed=15695812; DOI=10.1074/jbc.m413692200;
RA Hoashi T., Watabe H., Muller J., Yamaguchi Y., Vieira W.D., Hearing V.J.;
RT "MART-1 is required for the function of the melanosomal matrix protein
RT PMEL17/GP100 and the maturation of melanosomes.";
RL J. Biol. Chem. 280:14006-14016(2005).
RN [19]
RP DOMAIN RPT, AND DOMAIN LUMENAL.
RX PubMed=16682408; DOI=10.1074/jbc.m601643200;
RA Hoashi T., Muller J., Vieira W.D., Rouzaud F., Kikuchi K., Tamaki K.,
RA Hearing V.J.;
RT "The repeat domain of the melanosomal matrix protein PMEL17/GP100 is
RT required for the formation of organellar fibers.";
RL J. Biol. Chem. 281:21198-21208(2006).
RN [20]
RP SUBCELLULAR LOCATION [LARGE SCALE ANALYSIS].
RC TISSUE=Melanoma;
RX PubMed=17081065; DOI=10.1021/pr060363j;
RA Chi A., Valencia J.C., Hu Z.-Z., Watabe H., Yamaguchi H., Mangini N.J.,
RA Huang H., Canfield V.A., Cheng K.C., Yang F., Abe R., Yamagishi S.,
RA Shabanowitz J., Hearing V.J., Wu C., Appella E., Hunt D.F.;
RT "Proteomic and bioinformatic characterization of the biogenesis and
RT function of melanosomes.";
RL J. Proteome Res. 5:3135-3144(2006).
RN [21]
RP PROTEOLYTIC PROCESSING, AND GLYCOSYLATION.
RX PubMed=17991747; DOI=10.1074/jbc.m708007200;
RA Harper D.C., Theos A.C., Herman K.E., Tenza D., Raposo G., Marks M.S.;
RT "Premelanosome amyloid-like fibrils are composed of only Golgi-processed
RT forms of Pmel17 that have been proteolytically processed in endosomes.";
RL J. Biol. Chem. 283:2307-2322(2008).
RN [22]
RP FUNCTION, SUBCELLULAR LOCATION, AND INTERACTION WITH CD63.
RX PubMed=21962903; DOI=10.1016/j.devcel.2011.08.019;
RA van Niel G., Charrin S., Simoes S., Romao M., Rochin L., Saftig P.,
RA Marks M.S., Rubinstein E., Raposo G.;
RT "The tetraspanin CD63 regulates ESCRT-independent and -dependent endosomal
RT sorting during melanogenesis.";
RL Dev. Cell 21:708-721(2011).
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. Release of the soluble form, ME20-S, could
CC protect tumor cells from antibody mediated immunity.
CC {ECO:0000269|PubMed:11694580, ECO:0000269|PubMed:21962903}.
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. {ECO:0000269|PubMed:11694580,
CC ECO:0000269|PubMed:15695812, ECO:0000269|PubMed:21962903}.
CC -!- INTERACTION:
CC P40967; P40967: PMEL; NbExp=4; IntAct=EBI-14022409, EBI-14022409;
CC P40967-2; P40967-2: PMEL; NbExp=4; IntAct=EBI-15894236, EBI-15894236;
CC -!- SUBCELLULAR LOCATION: Endoplasmic reticulum membrane; Single-pass type
CC I membrane protein. Golgi apparatus. Melanosome. Endosome,
CC multivesicular body. Note=Identified by mass spectrometry in melanosome
CC fractions from stage I to stage IV. Localizes predominantly to
CC intralumenal vesicles (ILVs) within multivesicular bodies. Associates
CC with ILVs found within the lumen of premelanosomes and melanosomes and
CC particularly in compartments that serve as precursors to the striated
CC stage II premelanosomes.
CC -!- SUBCELLULAR LOCATION: [M-alpha]: Secreted.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=5;
CC Name=1; Synonyms=Intermediate form, Pmel17-i;
CC IsoId=P40967-1; Sequence=Displayed;
CC Name=2; Synonyms=Long form, Pmel17-l;
CC IsoId=P40967-2; Sequence=VSP_038268;
CC Name=3;
CC IsoId=P40967-3; Sequence=VSP_038266;
CC Name=4; Synonyms=Short form, Pmel17-ls;
CC IsoId=P40967-4; Sequence=VSP_038267;
CC Name=5; Synonyms=Short form, Pmel17-is;
CC IsoId=P40967-5; Sequence=VSP_038267, VSP_038268;
CC -!- TISSUE SPECIFICITY: Preferentially expressed in melanomas. Some
CC expression was found in dysplastic nevi. Not found in normal tissues
CC nor in carcinomas. Normally expressed at low levels in quiescent adult
CC melanocytes but overexpressed by proliferating neonatal melanocytes and
CC during tumor growth.
CC -!- DOMAIN: The RPT domain is essential for the generation of the fibrillar
CC matrix of melanosomes. {ECO:0000269|PubMed:16682408}.
CC -!- DOMAIN: The lumenal domain is necessary for correct processing and
CC trafficking to melanosomes. {ECO:0000269|PubMed:16682408}.
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.
CC {ECO:0000269|PubMed:11694580, ECO:0000269|PubMed:12732614,
CC ECO:0000269|PubMed:15096515, ECO:0000269|PubMed:15695812,
CC ECO:0000269|PubMed:17991747}.
CC -!- PTM: N-glycosylated. O-glycosylated; contains sialic acid.
CC -!- SIMILARITY: Belongs to the PMEL/NMB family. {ECO:0000305}.
CC -!- SEQUENCE CAUTION:
CC Sequence=AAA35930.1; Type=Erroneous initiation; Note=Truncated N-terminus.; Evidence={ECO:0000305};
CC Sequence=AAA35930.1; Type=Frameshift; Evidence={ECO:0000305};
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DR EMBL; M77348; AAA60121.1; -; mRNA.
DR EMBL; U01874; AAA18479.1; -; mRNA.
DR EMBL; S73003; AAC60634.1; -; mRNA.
DR EMBL; U31799; AAB00386.1; -; Genomic_DNA.
DR EMBL; U31808; AAB00386.1; JOINED; Genomic_DNA.
DR EMBL; U31807; AAB00386.1; JOINED; Genomic_DNA.
DR EMBL; U31797; AAB00386.1; JOINED; Genomic_DNA.
DR EMBL; U31798; AAB00386.1; JOINED; Genomic_DNA.
DR EMBL; U20093; AAB19181.1; -; Genomic_DNA.
DR EMBL; U19491; AAB19181.1; JOINED; Genomic_DNA.
DR EMBL; M32295; AAA35930.1; ALT_SEQ; mRNA.
DR EMBL; BT007202; AAP35866.1; -; mRNA.
DR EMBL; AK092881; BAG52619.1; -; mRNA.
DR EMBL; AK300150; BAH13223.1; -; mRNA.
DR EMBL; AC025162; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CH471054; EAW96853.1; -; Genomic_DNA.
DR EMBL; BC001414; AAH01414.1; -; mRNA.
DR CCDS; CCDS55833.1; -. [P40967-3]
DR CCDS; CCDS55834.1; -. [P40967-2]
DR CCDS; CCDS8897.1; -. [P40967-1]
DR PIR; A41234; A41234.
DR PIR; I38400; I38400.
DR RefSeq; NP_001186982.1; NM_001200053.1. [P40967-3]
DR RefSeq; NP_001186983.1; NM_001200054.1. [P40967-2]
DR RefSeq; NP_001307050.1; NM_001320121.1. [P40967-5]
DR RefSeq; NP_001307051.1; NM_001320122.1. [P40967-4]
DR RefSeq; NP_008859.1; NM_006928.4. [P40967-1]
DR RefSeq; XP_006719632.1; XM_006719569.1.
DR RefSeq; XP_011536987.1; XM_011538685.1.
DR PDB; 1TVB; X-ray; 1.80 A; C/F=209-217.
DR PDB; 1TVH; X-ray; 1.80 A; C/F=209-217.
DR PDB; 3CC5; X-ray; 1.91 A; C/F=25-33.
DR PDB; 4IS6; X-ray; 2.50 A; C=44-59.
DR PDB; 5EU3; X-ray; 1.97 A; C=280-288.
DR PDB; 5EU4; X-ray; 2.12 A; C/F=280-288.
DR PDB; 5EU5; X-ray; 1.54 A; C=280-288.
DR PDB; 5EU6; X-ray; 2.02 A; C=280-287.
DR PDB; 6VM7; X-ray; 2.41 A; C=209-217.
DR PDB; 6VM8; X-ray; 2.41 A; C=209-217.
DR PDB; 6VM9; X-ray; 2.90 A; C=209-217.
DR PDB; 6VMA; X-ray; 2.75 A; C=209-217.
DR PDB; 6VMC; X-ray; 2.85 A; C=209-217.
DR PDBsum; 1TVB; -.
DR PDBsum; 1TVH; -.
DR PDBsum; 3CC5; -.
DR PDBsum; 4IS6; -.
DR PDBsum; 5EU3; -.
DR PDBsum; 5EU4; -.
DR PDBsum; 5EU5; -.
DR PDBsum; 5EU6; -.
DR PDBsum; 6VM7; -.
DR PDBsum; 6VM8; -.
DR PDBsum; 6VM9; -.
DR PDBsum; 6VMA; -.
DR PDBsum; 6VMC; -.
DR AlphaFoldDB; P40967; -.
DR SMR; P40967; -.
DR BioGRID; 112381; 69.
DR DIP; DIP-48937N; -.
DR IntAct; P40967; 50.
DR STRING; 9606.ENSP00000402758; -.
DR ChEMBL; CHEMBL3712988; -.
DR GlyGen; P40967; 5 sites.
DR iPTMnet; P40967; -.
DR PhosphoSitePlus; P40967; -.
DR BioMuta; PMEL; -.
DR DMDM; 2507099; -.
DR EPD; P40967; -.
DR jPOST; P40967; -.
DR MassIVE; P40967; -.
DR PaxDb; P40967; -.
DR PeptideAtlas; P40967; -.
DR PRIDE; P40967; -.
DR ProteomicsDB; 55393; -. [P40967-1]
DR ProteomicsDB; 55394; -. [P40967-2]
DR ProteomicsDB; 55395; -. [P40967-3]
DR ProteomicsDB; 55396; -. [P40967-4]
DR ProteomicsDB; 55397; -. [P40967-5]
DR ABCD; P40967; 14 sequenced antibodies.
DR Antibodypedia; 746; 1123 antibodies from 38 providers.
DR DNASU; 6490; -.
DR Ensembl; ENST00000449260.6; ENSP00000402758.2; ENSG00000185664.15. [P40967-2]
DR Ensembl; ENST00000548493.5; ENSP00000447374.1; ENSG00000185664.15. [P40967-1]
DR Ensembl; ENST00000548747.6; ENSP00000448828.1; ENSG00000185664.15. [P40967-1]
DR Ensembl; ENST00000550464.5; ENSP00000450036.1; ENSG00000185664.15. [P40967-3]
DR Ensembl; ENST00000552882.5; ENSP00000449690.1; ENSG00000185664.15. [P40967-1]
DR GeneID; 6490; -.
DR KEGG; hsa:6490; -.
DR MANE-Select; ENST00000548747.6; ENSP00000448828.1; NM_001384361.1; NP_001371290.1.
DR UCSC; uc001sip.4; human. [P40967-1]
DR CTD; 6490; -.
DR DisGeNET; 6490; -.
DR GeneCards; PMEL; -.
DR HGNC; HGNC:10880; PMEL.
DR HPA; ENSG00000185664; Group enriched (cervix, endometrium, skin).
DR MIM; 155550; gene.
DR neXtProt; NX_P40967; -.
DR OpenTargets; ENSG00000185664; -.
DR PharmGKB; PA35781; -.
DR VEuPathDB; HostDB:ENSG00000185664; -.
DR eggNOG; ENOG502QV5K; Eukaryota.
DR GeneTree; ENSGT00950000183188; -.
DR HOGENOM; CLU_017264_0_0_1; -.
DR InParanoid; P40967; -.
DR OMA; GPRDQDW; -.
DR OrthoDB; 393436at2759; -.
DR PhylomeDB; P40967; -.
DR TreeFam; TF334865; -.
DR PathwayCommons; P40967; -.
DR SignaLink; P40967; -.
DR SIGNOR; P40967; -.
DR BioGRID-ORCS; 6490; 8 hits in 1067 CRISPR screens.
DR ChiTaRS; PMEL; human.
DR EvolutionaryTrace; P40967; -.
DR GeneWiki; PMEL_(gene); -.
DR GenomeRNAi; 6490; -.
DR Pharos; P40967; Tbio.
DR PRO; PR:P40967; -.
DR Proteomes; UP000005640; Chromosome 12.
DR RNAct; P40967; protein.
DR Bgee; ENSG00000185664; Expressed in pigmented layer of retina and 114 other tissues.
DR ExpressionAtlas; P40967; baseline and differential.
DR Genevisible; P40967; HS.
DR GO; GO:0005783; C:endoplasmic reticulum; IDA:HPA.
DR GO; GO:0005789; C:endoplasmic reticulum membrane; IDA:UniProtKB.
DR GO; GO:0005576; C:extracellular region; IEA:UniProtKB-SubCell.
DR GO; GO:0005794; C:Golgi apparatus; IDA:UniProtKB.
DR GO; GO:0005887; C:integral component of plasma membrane; IBA:GO_Central.
DR GO; GO:0042470; C:melanosome; IDA:UniProtKB.
DR GO; GO:0032585; C:multivesicular body membrane; IDA:UniProtKB.
DR GO; GO:0005886; C:plasma membrane; TAS:ProtInc.
DR GO; GO:0042802; F:identical protein binding; IPI:IntAct.
DR GO; GO:0042438; P:melanin biosynthetic process; IEA:UniProtKB-KW.
DR GO; GO:0032438; P:melanosome organization; IDA:UniProtKB.
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; 1.
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 3D-structure; Alternative splicing; Cleavage on pair of basic residues;
KW Direct protein sequencing; Disulfide bond; Endoplasmic reticulum; Endosome;
KW 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:0000269|PubMed:8179825"
FT CHAIN 25..661
FT /note="Melanocyte protein PMEL"
FT /id="PRO_0000024712"
FT CHAIN 25..467
FT /note="M-alpha"
FT /id="PRO_0000292263"
FT CHAIN 470..661
FT /note="M-beta"
FT /id="PRO_0000386648"
FT TOPO_DOM 470..595
FT /note="Lumenal"
FT /evidence="ECO:0000255"
FT TRANSMEM 596..616
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 617..661
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..405
FT /note="7"
FT REPEAT 406..418
FT /note="8"
FT REPEAT 419..431
FT /note="9"
FT REPEAT 432..444
FT /note="10"
FT REGION 302..353
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 315..444
FT /note="10 X 13 AA approximate tandem repeats, RPT domain"
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 321
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 568
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT VAR_SEQ 26..111
FT /note="Missing (in isoform 3)"
FT /evidence="ECO:0000303|PubMed:14702039"
FT /id="VSP_038266"
FT VAR_SEQ 373..414
FT /note="Missing (in isoform 4 and isoform 5)"
FT /evidence="ECO:0000305"
FT /id="VSP_038267"
FT VAR_SEQ 587
FT /note="P -> PVPGILLT (in isoform 2 and isoform 5)"
FT /evidence="ECO:0000303|PubMed:1924386"
FT /id="VSP_038268"
FT VARIANT 320
FT /note="P -> H (in dbSNP:rs2071024)"
FT /id="VAR_050606"
FT VARIANT 370
FT /note="E -> D (in dbSNP:rs17118154)"
FT /id="VAR_050607"
FT MUTAGEN 468..469
FT /note="KR->QQ: Loss of proteolytic cleavage."
FT /evidence="ECO:0000269|PubMed:12732614"
FT CONFLICT 162
FT /note="V -> F (in Ref. 4; no nucleotide entry)"
FT /evidence="ECO:0000305"
FT CONFLICT 274
FT /note="L -> P (in Ref. 1; AAA60121 and 6; AAB19181)"
FT /evidence="ECO:0000305"
FT CONFLICT 373
FT /note="G -> S (in Ref. 9; BAH13223)"
FT /evidence="ECO:0000305"
FT CONFLICT 592
FT /note="G -> GG (in Ref. 2; AA sequence)"
FT /evidence="ECO:0000305"
FT CONFLICT 597
FT /note="P -> R (in Ref. 1; AAA60121)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 661 AA; 70255 MW; 8A904FAB16715653 CRC64;
MDLVLKRCLL HLAVIGALLA VGATKVPRNQ DWLGVSRQLR TKAWNRQLYP EWTEAQRLDC
WRGGQVSLKV SNDGPTLIGA NASFSIALNF PGSQKVLPDG QVIWVNNTII NGSQVWGGQP
VYPQETDDAC IFPDGGPCPS GSWSQKRSFV YVWKTWGQYW QVLGGPVSGL SIGTGRAMLG
THTMEVTVYH RRGSRSYVPL AHSSSAFTIT DQVPFSVSVS QLRALDGGNK HFLRNQPLTF
ALQLHDPSGY LAEADLSYTW DFGDSSGTLI SRALVVTHTY LEPGPVTAQV VLQAAIPLTS
CGSSPVPGTT DGHRPTAEAP NTTAGQVPTT EVVGTTPGQA PTAEPSGTTS VQVPTTEVIS
TAPVQMPTAE STGMTPEKVP VSEVMGTTLA EMSTPEATGM TPAEVSIVVL SGTTAAQVTT
TEWVETTARE LPIPEPEGPD ASSIMSTESI TGSLGPLLDG TATLRLVKRQ VPLDCVLYRY
GSFSVTLDIV QGIESAEILQ AVPSGEGDAF ELTVSCQGGL PKEACMEISS PGCQPPAQRL
CQPVLPSPAC QLVLHQILKG GSGTYCLNVS LADTNSLAVV STQLIMPGQE AGLGQVPLIV
GILLVLMAVV LASLIYRRRL MKQDFSVPQL PHSSSHWLRL PRIFCSCPIG ENSPLLSGQQ
V
