CD63_HUMAN
ID CD63_HUMAN Reviewed; 238 AA.
AC P08962; F8VZE2; Q5TZP3; Q8N6Z9; Q9UCG6;
DT 01-NOV-1988, integrated into UniProtKB/Swiss-Prot.
DT 23-JAN-2007, sequence version 2.
DT 03-AUG-2022, entry version 215.
DE RecName: Full=CD63 antigen;
DE AltName: Full=Granulophysin;
DE AltName: Full=Lysosomal-associated membrane protein 3 {ECO:0000303|PubMed:10793155, ECO:0000303|PubMed:1939168};
DE Short=LAMP-3 {ECO:0000303|PubMed:10793155, ECO:0000303|PubMed:1939168};
DE AltName: Full=Lysosome integral membrane protein 1 {ECO:0000303|PubMed:1939168};
DE Short=Limp1 {ECO:0000303|PubMed:1939168};
DE AltName: Full=Melanoma-associated antigen ME491 {ECO:0000303|PubMed:1599482, ECO:0000303|PubMed:1939168};
DE AltName: Full=OMA81H;
DE AltName: Full=Ocular melanoma-associated antigen;
DE AltName: Full=Tetraspanin-30;
DE Short=Tspan-30;
DE AltName: CD_antigen=CD63;
GN Name=CD63; Synonyms=MLA1, TSPAN30;
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 1).
RX PubMed=3365686;
RA Hotta H., Ross A.H., Huebner K., Isobe M., Wendeborn S., Chao M.V.,
RA Ricciardi R.P., Tsujimoto Y., Croce C.M., Koprowski H.;
RT "Molecular cloning and characterization of an antigen associated with early
RT stages of melanoma tumor progression.";
RL Cancer Res. 48:2955-2962(1988).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
RC TISSUE=Ovary;
RX PubMed=2171551; DOI=10.1089/dna.1990.9.479;
RA Rapp G., Freudenstein J., Klaudiny J., Mucha J., Wempe F., Zimmer M.,
RA Scheit K.H.;
RT "Characterization of three abundant mRNAs from human ovarian granulosa
RT cells.";
RL DNA Cell Biol. 9:479-485(1990).
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), AND SUBCELLULAR LOCATION.
RX PubMed=1993697; DOI=10.1016/s0021-9258(18)49980-2;
RA Metzelaar M.J., Wigngaard P.L., Peters P.J., Sixma J.J., Nieuwenhuis H.K.,
RA Clevers H.C.;
RT "CD63 antigen. A novel lysosomal membrane glycoprotein, cloned by a
RT screening procedure for intracellular antigens in eukaryotic cells.";
RL J. Biol. Chem. 266:3239-3245(1991).
RN [4]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
RX PubMed=1339263; DOI=10.1001/archopht.1992.01080150097036;
RA Wang M.X., Earley J.J. Jr., Shields J.A., Donoso L.A.;
RT "An ocular melanoma-associated antigen. Molecular characterization.";
RL Arch. Ophthalmol. 110:399-404(1992).
RN [5]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RX PubMed=1599482; DOI=10.1016/s0006-291x(05)81004-6;
RA Hotta H., Miyamoto H., Hara I., Takahashi N., Homma M.;
RT "Genomic structure of the ME491/CD63 antigen gene and functional analysis
RT of the 5'-flanking regulatory sequences.";
RL Biochem. Biophys. Res. Commun. 185:436-442(1992).
RN [6]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2).
RC TISSUE=Skin;
RA Ancans J., Suzuki I., Thody A.J.;
RT "Melanocyte variant of lysosome-associated membrane protein-3 (LAMP3; also
RT CD63 and melanoma associated antigen ME419) mRNA.";
RL Submitted (MAY-2002) to the EMBL/GenBank/DDBJ databases.
RN [7]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC TISSUE=Skeletal muscle;
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 [8]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RA Halleck A., Ebert L., Mkoundinya M., Schick M., Eisenstein S., Neubert P.,
RA Kstrang K., Schatten R., Shen B., Henze S., Mar W., Korn B., Zuo D., Hu Y.,
RA LaBaer J.;
RT "Cloning of human full open reading frames in Gateway(TM) system entry
RT vector (pDONR201).";
RL Submitted (JUN-2004) to the EMBL/GenBank/DDBJ databases.
RN [9]
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 (OCT-2004) to the EMBL/GenBank/DDBJ databases.
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=Lung, and Muscle;
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 PROTEIN SEQUENCE OF 2-38 (ISOFORM 1), SUBCELLULAR LOCATION, AND LACK OF
RP EXPRESSION IN HERMANSKY-PUDLAK SYNDROME.
RC TISSUE=Platelet;
RX PubMed=7682577; DOI=10.1172/jci116388;
RA Nishibori M., Cham B., McNicol A., Shalev A., Jain N., Gerrard J.M.;
RT "The protein CD63 is in platelet dense granules, is deficient in a patient
RT with Hermansky-Pudlak syndrome, and appears identical to granulophysin.";
RL J. Clin. Invest. 91:1775-1782(1993).
RN [14]
RP PROTEIN SEQUENCE OF 2-21 (ISOFORMS 1/2).
RX PubMed=4062294; DOI=10.1016/0003-9861(85)90241-3;
RA Ross A.H., Dietzschold B., Jackson D.M., Earley J.J., Ghrist B.F.D.,
RA Atkinson B., Koprowski H.;
RT "Isolation and amino terminal sequencing of a novel melanoma-associated
RT antigen.";
RL Arch. Biochem. Biophys. 242:540-548(1985).
RN [15]
RP REVIEW, AND NOMENCLATURE.
RX PubMed=1939168; DOI=10.1016/s0021-9258(18)54636-6;
RA Fukuda M.;
RT "Lysosomal membrane glycoproteins. Structure, biosynthesis, and
RT intracellular trafficking.";
RL J. Biol. Chem. 266:21327-21330(1991).
RN [16]
RP SUBCELLULAR LOCATION.
RX PubMed=10793155; DOI=10.1091/mbc.11.5.1829;
RA Kobayashi T., Vischer U.M., Rosnoblet C., Lebrand C., Lindsay M.,
RA Parton R.G., Kruithof E.K.O., Gruenberg J.;
RT "The tetraspanin CD63/lamp3 cycles between endocytic and secretory
RT compartments in human endothelial cells.";
RL Mol. Biol. Cell 11:1829-1843(2000).
RN [17]
RP GLYCOSYLATION AT ASN-130.
RX PubMed=12754519; DOI=10.1038/nbt827;
RA Zhang H., Li X.-J., Martin D.B., Aebersold R.;
RT "Identification and quantification of N-linked glycoproteins using
RT hydrazide chemistry, stable isotope labeling and mass spectrometry.";
RL Nat. Biotechnol. 21:660-666(2003).
RN [18]
RP SUBCELLULAR LOCATION.
RX PubMed=15351990; DOI=10.1002/cyto.a.20068;
RA Gruetzkau A., Smorodchenko A., Lippert U., Kirchhof L., Artuc M.,
RA Henz B.M.;
RT "LAMP-1 and LAMP-2, but not LAMP-3, are reliable markers for activation-
RT induced secretion of human mast cells.";
RL Cytometry 61:62-68(2004).
RN [19]
RP FUNCTION, SUBCELLULAR LOCATION, AND INTERACTION WITH TIMP1 AND ITGB1.
RX PubMed=16917503; DOI=10.1038/sj.emboj.7601281;
RA Jung K.K., Liu X.W., Chirco R., Fridman R., Kim H.R.;
RT "Identification of CD63 as a tissue inhibitor of metalloproteinase-1
RT interacting cell surface protein.";
RL EMBO J. 25:3934-3942(2006).
RN [20]
RP SUBCELLULAR LOCATION [LARGE SCALE ANALYSIS].
RC TISSUE=Placenta;
RX PubMed=17897319; DOI=10.1111/j.1600-0854.2007.00643.x;
RA Schroeder B., Wrocklage C., Pan C., Jaeger R., Koesters B., Schaefer H.,
RA Elsaesser H.-P., Mann M., Hasilik A.;
RT "Integral and associated lysosomal membrane proteins.";
RL Traffic 8:1676-1686(2007).
RN [21]
RP GLYCOSYLATION [LARGE SCALE ANALYSIS] AT ASN-130.
RC TISSUE=Liver;
RX PubMed=19159218; DOI=10.1021/pr8008012;
RA Chen R., Jiang X., Sun D., Han G., Wang F., Ye M., Wang L., Zou H.;
RT "Glycoproteomics analysis of human liver tissue by combination of multiple
RT enzyme digestion and hydrazide chemistry.";
RL J. Proteome Res. 8:651-661(2009).
RN [22]
RP PALMITOYLATION, SUBCELLULAR LOCATION, TISSUE SPECIFICITY, INTERACTION WITH
RP CD9, AND IDENTIFICATION IN A COMPLEX WITH ITGB3.
RX PubMed=19640571; DOI=10.1016/j.thromres.2009.07.005;
RA Israels S.J., McMillan-Ward E.M.;
RT "Palmitoylation supports the association of tetraspanin CD63 with CD9 and
RT integrin alphaIIbbeta3 in activated platelets.";
RL Thromb. Res. 125:152-158(2010).
RN [23]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=21269460; DOI=10.1186/1752-0509-5-17;
RA Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T.,
RA Bennett K.L., Superti-Furga G., Colinge J.;
RT "Initial characterization of the human central proteome.";
RL BMC Syst. Biol. 5:17-17(2011).
RN [24]
RP FUNCTION IN CELL-CELL ADHESION, AND SUBCELLULAR LOCATION.
RX PubMed=21803846; DOI=10.1182/blood-2010-11-321489;
RA Doyle E.L., Ridger V., Ferraro F., Turmaine M., Saftig P., Cutler D.F.;
RT "CD63 is an essential cofactor to leukocyte recruitment by endothelial P-
RT selectin.";
RL Blood 118:4265-4273(2011).
RN [25]
RP FUNCTION IN MELANOCYTE DEVELOPMENT, SUBCELLULAR LOCATION, AND INTERACTION
RP WITH PMEL.
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).
RN [26]
RP SUBCELLULAR LOCATION.
RX PubMed=22431521; DOI=10.1128/mcb.06726-11;
RA Mamo A., Jules F., Dumaresq-Doiron K., Costantino S., Lefrancois S.;
RT "The role of ceroid lipofuscinosis neuronal protein 5 (CLN5) in endosomal
RT sorting.";
RL Mol. Cell. Biol. 32:1855-1866(2012).
RN [27]
RP SUBCELLULAR LOCATION.
RX PubMed=22660413; DOI=10.1038/ncb2502;
RA Baietti M.F., Zhang Z., Mortier E., Melchior A., Degeest G., Geeraerts A.,
RA Ivarsson Y., Depoortere F., Coomans C., Vermeiren E., Zimmermann P.,
RA David G.;
RT "Syndecan-syntenin-ALIX regulates the biogenesis of exosomes.";
RL Nat. Cell Biol. 14:677-685(2012).
RN [28]
RP FUNCTION, SUBCELLULAR LOCATION, AND INTERACTION WITH KDR.
RX PubMed=23632027; DOI=10.1074/jbc.m113.468199;
RA Tugues S., Honjo S., Konig C., Padhan N., Kroon J., Gualandi L., Li X.,
RA Barkefors I., Thijssen V.L., Griffioen A.W., Claesson-Welsh L.;
RT "Tetraspanin CD63 promotes vascular endothelial growth factor receptor 2-
RT beta1 integrin complex formation, thereby regulating activation and
RT downstream signaling in endothelial cells in vitro and in vivo.";
RL J. Biol. Chem. 288:19060-19071(2013).
RN [29]
RP FUNCTION, AND INTERACTION WITH ITGB1.
RX PubMed=24635319; DOI=10.1042/bj20131119;
RA Lee S.Y., Kim J.M., Cho S.Y., Kim H.S., Shin H.S., Jeon J.Y., Kausar R.,
RA Jeong S.Y., Lee Y.S., Lee M.A.;
RT "TIMP-1 modulates chemotaxis of human neural stem cells through CD63 and
RT integrin signalling.";
RL Biochem. J. 459:565-576(2014).
RN [30]
RP CLEAVAGE OF INITIATOR METHIONINE [LARGE SCALE ANALYSIS], AND IDENTIFICATION
RP BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=25944712; DOI=10.1002/pmic.201400617;
RA Vaca Jacome A.S., Rabilloud T., Schaeffer-Reiss C., Rompais M., Ayoub D.,
RA Lane L., Bairoch A., Van Dorsselaer A., Carapito C.;
RT "N-terminome analysis of the human mitochondrial proteome.";
RL Proteomics 15:2519-2524(2015).
CC -!- FUNCTION: Functions as cell surface receptor for TIMP1 and plays a role
CC in the activation of cellular signaling cascades. Plays a role in the
CC activation of ITGB1 and integrin signaling, leading to the activation
CC of AKT, FAK/PTK2 and MAP kinases. Promotes cell survival,
CC reorganization of the actin cytoskeleton, cell adhesion, spreading and
CC migration, via its role in the activation of AKT and FAK/PTK2. Plays a
CC role in VEGFA signaling via its role in regulating the internalization
CC of KDR/VEGFR2. Plays a role in intracellular vesicular transport
CC processes, and is required for normal trafficking of the PMEL luminal
CC domain that is essential for the development and maturation of
CC melanocytes. Plays a role in the adhesion of leukocytes onto
CC endothelial cells via its role in the regulation of SELP trafficking.
CC May play a role in mast cell degranulation in response to Ms4a2/FceRI
CC stimulation, but not in mast cell degranulation in response to other
CC stimuli. {ECO:0000269|PubMed:16917503, ECO:0000269|PubMed:21803846,
CC ECO:0000269|PubMed:21962903, ECO:0000269|PubMed:23632027,
CC ECO:0000269|PubMed:24635319}.
CC -!- SUBUNIT: Interacts with TIMP1 and ITGB1 and recruits TIMP1 to ITGB1
CC (PubMed:16917503, PubMed:24635319). Interacts with CD9. Identified in a
CC complex with CD9 and ITGB3 (PubMed:19640571). Interacts with PMEL
CC (PubMed:21962903). Interacts with KDR/VEGFR2; identified in a complex
CC with ITGB1 and KDR/VEGFR2 and is required to recruit KDR to ITGB1
CC complexes (PubMed:23632027). Interacts with SYT7 (By similarity).
CC {ECO:0000250|UniProtKB:P41731, ECO:0000269|PubMed:16917503,
CC ECO:0000269|PubMed:19640571, ECO:0000269|PubMed:21962903,
CC ECO:0000269|PubMed:23632027, ECO:0000269|PubMed:24635319}.
CC -!- INTERACTION:
CC P08962; P01033: TIMP1; NbExp=8; IntAct=EBI-762053, EBI-712536;
CC P08962; Q96HE8: TMEM80; NbExp=3; IntAct=EBI-762053, EBI-11742770;
CC P08962; PRO_0000038428 [P04578]: env; Xeno; NbExp=4; IntAct=EBI-762053, EBI-6179711;
CC -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000269|PubMed:15351990,
CC ECO:0000269|PubMed:19640571, ECO:0000269|PubMed:23632027}; Multi-pass
CC membrane protein {ECO:0000255}. Lysosome membrane
CC {ECO:0000269|PubMed:17897319, ECO:0000269|PubMed:19640571,
CC ECO:0000269|PubMed:1993697, ECO:0000269|PubMed:22431521,
CC ECO:0000269|PubMed:23632027}; Multi-pass membrane protein
CC {ECO:0000255}. Late endosome membrane {ECO:0000269|PubMed:10793155,
CC ECO:0000269|PubMed:23632027}; Multi-pass membrane protein
CC {ECO:0000255}. Endosome, multivesicular body
CC {ECO:0000269|PubMed:21962903}. Melanosome
CC {ECO:0000269|PubMed:21962903}. Secreted, extracellular exosome
CC {ECO:0000269|PubMed:22660413}. Cell surface
CC {ECO:0000269|PubMed:16917503, ECO:0000269|PubMed:23632027,
CC ECO:0000269|PubMed:24635319}. Note=Also found in Weibel-Palade bodies
CC of endothelial cells (PubMed:10793155). Located in platelet dense
CC granules (PubMed:7682577). Detected in a subset of pre-melanosomes.
CC Detected on intralumenal vesicles (ILVs) within multivesicular bodies
CC (PubMed:21962903). {ECO:0000269|PubMed:10793155,
CC ECO:0000269|PubMed:21962903, ECO:0000269|PubMed:7682577}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=3;
CC Name=1;
CC IsoId=P08962-1; Sequence=Displayed;
CC Name=2;
CC IsoId=P08962-2; Sequence=VSP_045300;
CC Name=3;
CC IsoId=P08962-3; Sequence=VSP_046996;
CC -!- TISSUE SPECIFICITY: Detected in platelets (at protein level).
CC Dysplastic nevi, radial growth phase primary melanomas, hematopoietic
CC cells, tissue macrophages. {ECO:0000269|PubMed:19640571}.
CC -!- PTM: Palmitoylated at a low, basal level in unstimulated platelets. The
CC level of palmitoylation increases when platelets are activated by
CC thrombin (in vitro). {ECO:0000269|PubMed:19640571}.
CC -!- MISCELLANEOUS: Lack of expression of CD63 in platelets has been
CC observed in a patient with Hermansky-Pudlak syndrome (HPS). Hermansky-
CC Pudlak syndrome (HPS) is a genetically heterogeneous, rare, autosomal
CC recessive disorder characterized by oculocutaneous albinism, bleeding
CC due to platelet storage pool deficiency, and lysosomal storage defects.
CC This syndrome results from defects of diverse cytoplasmic organelles
CC including melanosomes, platelet dense granules and lysosomes. Ceroid
CC storage in the lungs is associated with pulmonary fibrosis, a common
CC cause of premature death in individuals with HPS.
CC -!- MISCELLANEOUS: This antigen is associated with early stages of melanoma
CC tumor progression.
CC -!- SIMILARITY: Belongs to the tetraspanin (TM4SF) family. {ECO:0000305}.
CC ---------------------------------------------------------------------------
CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms
CC Distributed under the Creative Commons Attribution (CC BY 4.0) License
CC ---------------------------------------------------------------------------
DR EMBL; X07982; CAA30792.1; -; mRNA.
DR EMBL; M59907; AAA63235.1; -; mRNA.
DR EMBL; M58485; -; NOT_ANNOTATED_CDS; mRNA.
DR EMBL; S93788; AAB21617.1; -; mRNA.
DR EMBL; X62654; CAA44519.1; -; Genomic_DNA.
DR EMBL; AF508304; AAM34259.1; -; mRNA.
DR EMBL; AK311893; BAG34834.1; -; mRNA.
DR EMBL; CR542096; CAG46893.1; -; mRNA.
DR EMBL; BT007073; AAP35736.1; -; mRNA.
DR EMBL; BT020137; AAV38939.1; -; mRNA.
DR EMBL; BT020138; AAV38940.1; -; mRNA.
DR EMBL; AC009779; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CH471054; EAW96827.1; -; Genomic_DNA.
DR EMBL; BC002349; AAH02349.1; -; mRNA.
DR EMBL; BC013017; AAH13017.1; -; mRNA.
DR CCDS; CCDS58242.1; -. [P08962-3]
DR CCDS; CCDS58243.1; -. [P08962-2]
DR CCDS; CCDS8890.1; -. [P08962-1]
DR PIR; I38016; I38016.
DR RefSeq; NP_001244318.1; NM_001257389.1. [P08962-1]
DR RefSeq; NP_001244319.1; NM_001257390.1. [P08962-1]
DR RefSeq; NP_001244320.1; NM_001257391.1. [P08962-1]
DR RefSeq; NP_001244321.1; NM_001257392.1. [P08962-2]
DR RefSeq; NP_001244329.1; NM_001257400.1. [P08962-3]
DR RefSeq; NP_001244330.1; NM_001257401.1. [P08962-3]
DR RefSeq; NP_001254627.1; NM_001267698.1. [P08962-1]
DR RefSeq; NP_001771.1; NM_001780.5. [P08962-1]
DR AlphaFoldDB; P08962; -.
DR SMR; P08962; -.
DR BioGRID; 107405; 98.
DR CORUM; P08962; -.
DR IntAct; P08962; 29.
DR MINT; P08962; -.
DR STRING; 9606.ENSP00000447730; -.
DR BindingDB; P08962; -.
DR ChEMBL; CHEMBL3713303; -.
DR TCDB; 8.A.40.1.19; the tetraspanin (tetraspanin) family.
DR GlyConnect; 1088; 18 N-Linked glycans (3 sites).
DR GlyGen; P08962; 5 sites, 18 N-linked glycans (3 sites).
DR iPTMnet; P08962; -.
DR PhosphoSitePlus; P08962; -.
DR SwissPalm; P08962; -.
DR BioMuta; CD63; -.
DR DMDM; 116026; -.
DR CPTAC; CPTAC-1281; -.
DR EPD; P08962; -.
DR jPOST; P08962; -.
DR MassIVE; P08962; -.
DR MaxQB; P08962; -.
DR PaxDb; P08962; -.
DR PeptideAtlas; P08962; -.
DR PRIDE; P08962; -.
DR ProteomicsDB; 29322; -.
DR ProteomicsDB; 52180; -. [P08962-1]
DR ProteomicsDB; 72253; -.
DR ABCD; P08962; 1 sequenced antibody.
DR Antibodypedia; 2770; 2071 antibodies from 48 providers.
DR DNASU; 967; -.
DR Ensembl; ENST00000257857.9; ENSP00000257857.4; ENSG00000135404.12. [P08962-1]
DR Ensembl; ENST00000420846.7; ENSP00000393502.3; ENSG00000135404.12. [P08962-1]
DR Ensembl; ENST00000546939.5; ENSP00000447356.1; ENSG00000135404.12. [P08962-3]
DR Ensembl; ENST00000549117.5; ENSP00000447730.1; ENSG00000135404.12. [P08962-1]
DR Ensembl; ENST00000550776.5; ENSP00000448091.1; ENSG00000135404.12. [P08962-3]
DR Ensembl; ENST00000552692.5; ENSP00000449337.1; ENSG00000135404.12. [P08962-1]
DR Ensembl; ENST00000552754.5; ENSP00000446807.1; ENSG00000135404.12. [P08962-2]
DR GeneID; 967; -.
DR KEGG; hsa:967; -.
DR MANE-Select; ENST00000257857.9; ENSP00000257857.4; NM_001780.6; NP_001771.1.
DR UCSC; uc001shn.5; human. [P08962-1]
DR CTD; 967; -.
DR DisGeNET; 967; -.
DR GeneCards; CD63; -.
DR HGNC; HGNC:1692; CD63.
DR HPA; ENSG00000135404; Low tissue specificity.
DR MIM; 155740; gene.
DR neXtProt; NX_P08962; -.
DR OpenTargets; ENSG00000135404; -.
DR PharmGKB; PA26231; -.
DR VEuPathDB; HostDB:ENSG00000135404; -.
DR eggNOG; KOG3882; Eukaryota.
DR GeneTree; ENSGT00940000156832; -.
DR HOGENOM; CLU_055524_6_1_1; -.
DR InParanoid; P08962; -.
DR OMA; MQEDFKC; -.
DR OrthoDB; 1467737at2759; -.
DR PhylomeDB; P08962; -.
DR TreeFam; TF316345; -.
DR PathwayCommons; P08962; -.
DR Reactome; R-HSA-114608; Platelet degranulation.
DR Reactome; R-HSA-6798695; Neutrophil degranulation.
DR SignaLink; P08962; -.
DR BioGRID-ORCS; 967; 14 hits in 1076 CRISPR screens.
DR ChiTaRS; CD63; human.
DR GeneWiki; CD63; -.
DR GenomeRNAi; 967; -.
DR Pharos; P08962; Tchem.
DR PRO; PR:P08962; -.
DR Proteomes; UP000005640; Chromosome 12.
DR RNAct; P08962; protein.
DR Bgee; ENSG00000135404; Expressed in stromal cell of endometrium and 214 other tissues.
DR ExpressionAtlas; P08962; baseline and differential.
DR Genevisible; P08962; HS.
DR GO; GO:0035577; C:azurophil granule membrane; TAS:Reactome.
DR GO; GO:0009986; C:cell surface; IDA:MGI.
DR GO; GO:0031904; C:endosome lumen; IDA:UniProtKB.
DR GO; GO:0010008; C:endosome membrane; IDA:UniProtKB.
DR GO; GO:0070062; C:extracellular exosome; IDA:UniProtKB.
DR GO; GO:0005615; C:extracellular space; IDA:UniProtKB.
DR GO; GO:0005887; C:integral component of plasma membrane; IBA:GO_Central.
DR GO; GO:0043231; C:intracellular membrane-bounded organelle; IDA:HPA.
DR GO; GO:0031226; C:intrinsic component of plasma membrane; IDA:UniProtKB.
DR GO; GO:0031902; C:late endosome membrane; IDA:UniProtKB.
DR GO; GO:0005765; C:lysosomal membrane; IDA:UniProtKB.
DR GO; GO:0042470; C:melanosome; IEA:UniProtKB-SubCell.
DR GO; GO:0032585; C:multivesicular body membrane; IDA:UniProtKB.
DR GO; GO:0097487; C:multivesicular body, internal vesicle; IDA:UniProtKB.
DR GO; GO:0005654; C:nucleoplasm; IDA:HPA.
DR GO; GO:0005886; C:plasma membrane; TAS:Reactome.
DR GO; GO:0031088; C:platelet dense granule membrane; TAS:Reactome.
DR GO; GO:0016477; P:cell migration; IMP:UniProtKB.
DR GO; GO:0007160; P:cell-matrix adhesion; IMP:UniProtKB.
DR GO; GO:0035646; P:endosome to melanosome transport; IMP:UniProtKB.
DR GO; GO:0048757; P:pigment granule maturation; IMP:UniProtKB.
DR GO; GO:2001046; P:positive regulation of integrin-mediated signaling pathway; IMP:UniProtKB.
DR GO; GO:0002092; P:positive regulation of receptor internalization; IMP:UniProtKB.
DR GO; GO:0015031; P:protein transport; IEA:UniProtKB-KW.
DR GO; GO:1901379; P:regulation of potassium ion transmembrane transport; IDA:MGI.
DR GO; GO:1900746; P:regulation of vascular endothelial growth factor signaling pathway; IMP:UniProtKB.
DR CDD; cd03166; CD63_LEL; 1.
DR Gene3D; 1.10.1450.10; -; 1.
DR InterPro; IPR042028; CD63_LEL.
DR InterPro; IPR018499; Tetraspanin/Peripherin.
DR InterPro; IPR000301; Tetraspanin_animals.
DR InterPro; IPR018503; Tetraspanin_CS.
DR InterPro; IPR008952; Tetraspanin_EC2_sf.
DR PANTHER; PTHR19282; PTHR19282; 1.
DR Pfam; PF00335; Tetraspanin; 1.
DR PIRSF; PIRSF002419; Tetraspanin; 1.
DR SUPFAM; SSF48652; SSF48652; 1.
DR PROSITE; PS00421; TM4_1; 1.
PE 1: Evidence at protein level;
KW Alternative splicing; Cell membrane; Direct protein sequencing; Endosome;
KW Glycoprotein; Lipoprotein; Lysosome; Membrane; Palmitate;
KW Protein transport; Reference proteome; Secreted; Transmembrane;
KW Transmembrane helix; Transport.
FT INIT_MET 1
FT /note="Removed"
FT /evidence="ECO:0007744|PubMed:25944712"
FT CHAIN 2..238
FT /note="CD63 antigen"
FT /id="PRO_0000219216"
FT TOPO_DOM 2..11
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 12..32
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 33..51
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 52..72
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 73..81
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 82..102
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 103..203
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 204..224
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 225..238
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT MOTIF 234..238
FT /note="Lysosomal targeting motif"
FT /evidence="ECO:0000250|UniProtKB:P41731"
FT CARBOHYD 130
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000269|PubMed:12754519,
FT ECO:0000269|PubMed:19159218"
FT CARBOHYD 150
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 172
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT VAR_SEQ 1..82
FT /note="Missing (in isoform 3)"
FT /evidence="ECO:0000305"
FT /id="VSP_046996"
FT VAR_SEQ 23..45
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|Ref.6"
FT /id="VSP_045300"
FT CONFLICT 36
FT /note="Q -> E (in Ref. 13; AA sequence)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 238 AA; 25637 MW; 85AC8E235C6E425F CRC64;
MAVEGGMKCV KFLLYVLLLA FCACAVGLIA VGVGAQLVLS QTIIQGATPG SLLPVVIIAV
GVFLFLVAFV GCCGACKENY CLMITFAIFL SLIMLVEVAA AIAGYVFRDK VMSEFNNNFR
QQMENYPKNN HTASILDRMQ ADFKCCGAAN YTDWEKIPSM SKNRVPDSCC INVTVGCGIN
FNEKAIHKEG CVEKIGGWLR KNVLVVAAAA LGIAFVEVLG IVFACCLVKS IRSGYEVM
