(data stored in ACNUC31108 zone)

SWISSPROT: 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   08-MAY-2019, entry version 196.
DE   RecName: Full=CD63 antigen;
DE   AltName: Full=Granulophysin;
DE   AltName: Full=Lysosomal-associated membrane protein 3;
DE            Short=LAMP-3;
DE   AltName: Full=Melanoma-associated antigen ME491;
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;
OC   Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini;
OC   Catarrhini; Hominidae; 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
RT   early 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;
RA   Metzelaar M.J., Wigngaard P.L., Peters P.J., Sixma J.J.,
RA   Nieuwenhuis H.K., 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
RT   analysis 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;
RT   also 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.,
RA   Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M.,
RA   Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y.,
RA   Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M.,
RA   Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K.,
RA   Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S.,
RA   Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J.,
RA   Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y.,
RA   Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N.,
RA   Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S.,
RA   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.,
RA   Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T.,
RA   Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y.,
RA   Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S.,
RA   Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T.,
RA   Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M.,
RA   Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T.,
RA   Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K.,
RA   Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R.,
RA   Nakai K., Yada T., Nakamura Y., Ohara O., 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.,
RA   Neubert P., Kstrang K., Schatten R., Shen B., Henze S., Mar W.,
RA   Korn B., Zuo D., Hu Y., 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
RT   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.,
RA   Kovar-Smith C., Lewis L.R., Lozado R.J., Metzker M.L.,
RA   Milosavljevic A., Miner G.R., Montgomery K.T., Morgan M.B.,
RA   Nazareth L.V., Scott G., Sodergren E., Song X.-Z., Steffen D.,
RA   Lovering R.C., Wheeler D.A., Worley K.C., Yuan Y., Zhang Z.,
RA   Adams C.Q., Ansari-Lari M.A., Ayele M., Brown M.J., Chen G., Chen Z.,
RA   Clerc-Blankenburg K.P., Davis C., Delgado O., Dinh H.H., Draper H.,
RA   Gonzalez-Garay M.L., Havlak P., Jackson L.R., Jacob L.S., Kelly S.H.,
RA   Li L., Li Z., Liu J., Liu W., Lu J., Maheshwari M., Nguyen B.-V.,
RA   Okwuonu G.O., Pasternak S., Perez L.M., Plopper F.J.H., Santibanez J.,
RA   Shen H., Tabor P.E., Verduzco D., Waldron L., Wang Q., Williams G.A.,
RA   Zhang J., Zhou J., Allen C.C., Amin A.G., Anyalebechi V., Bailey M.,
RA   Barbaria J.A., Bimage K.E., Bryant N.P., Burch P.E., Burkett C.E.,
RA   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.,
RA   Dathorne S.R., David R., Davis C.M., Davy-Carroll L., Deshazo D.R.,
RA   Donlin J.E., D'Souza L., Eaves K.A., Egan A., Emery-Cohen A.J.,
RA   Escotto M., Flagg N., Forbes L.D., Gabisi A.M., Garza M., Hamilton C.,
RA   Henderson N., Hernandez O., Hines S., Hogues M.E., Huang M.,
RA   Idlebird D.G., Johnson R., Jolivet A., Jones S., Kagan R., King L.M.,
RA   Leal B., Lebow H., Lee S., LeVan J.M., Lewis L.C., London P.,
RA   Lorensuhewa L.M., Loulseged H., Lovett D.A., Lucier A., Lucier R.L.,
RA   Ma J., Madu R.C., Mapua P., Martindale A.D., Martinez E., Massey E.,
RA   Mawhiney S., Meador M.G., Mendez S., Mercado C., Mercado I.C.,
RA   Merritt C.E., Miner Z.L., Minja E., Mitchell T., Mohabbat F.,
RA   Mohabbat K., Montgomery B., Moore N., Morris S., Munidasa M.,
RA   Ngo R.N., Nguyen N.B., Nickerson E., Nwaokelemeh O.O., Nwokenkwo S.,
RA   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.,
RA   Trejos Z.Y., Trevino B.K., Ukegbu O.N., Urban J.B., Vasquez L.I.,
RA   Vera V.A., Villasana D.M., Wang L., Ward-Moore S., Warren J.T.,
RA   Wei X., White F., Williamson A.L., Wleczyk R., Wooden H.S.,
RA   Wooden S.H., Yen J., Yoon L., Yoon V., Zorrilla S.E., Nelson D.,
RA   Kucherlapati R., Weinstock G., 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.,
RA   Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R.,
RA   Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V.,
RA   Hannenhalli S., Turner R., Yooseph S., Lu F., Nusskern D.R.,
RA   Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H.,
RA   Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G.,
RA   Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W.,
RA   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
RT   project: 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
RP   OF 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
RT   patient with Hermansky-Pudlak syndrome, and appears identical to
RT   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-
RT   associated antigen.";
RL   Arch. Biochem. Biophys. 242:540-548(1985).
RN   [15]
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   [16]
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   [17]
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
RT   activation-induced secretion of human mast cells.";
RL   Cytometry 61:62-68(2004).
RN   [18]
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   [19]
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.,
RA   Schaefer H., Elsaesser H.-P., Mann M., Hasilik A.;
RT   "Integral and associated lysosomal membrane proteins.";
RL   Traffic 8:1676-1686(2007).
RN   [20]
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
RT   multiple enzyme digestion and hydrazide chemistry.";
RL   J. Proteome Res. 8:651-661(2009).
RN   [21]
RP   PALMITOYLATION, SUBCELLULAR LOCATION, TISSUE SPECIFICITY, INTERACTION
RP   WITH 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
RT   and integrin alphaIIbbeta3 in activated platelets.";
RL   Thromb. Res. 125:152-158(2010).
RN   [22]
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.,
RA   Buerckstuemmer T., 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   [23]
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.,
RA   Cutler D.F.;
RT   "CD63 is an essential cofactor to leukocyte recruitment by endothelial
RT   P-selectin.";
RL   Blood 118:4265-4273(2011).
RN   [24]
RP   FUNCTION IN MELANOCYTE DEVELOPMENT, SUBCELLULAR LOCATION, AND
RP   INTERACTION 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
RT   endosomal sorting during melanogenesis.";
RL   Dev. Cell 21:708-721(2011).
RN   [25]
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
RT   endosomal sorting.";
RL   Mol. Cell. Biol. 32:1855-1866(2012).
RN   [26]
RP   SUBCELLULAR LOCATION.
RX   PubMed=22660413; DOI=10.1038/ncb2502;
RA   Baietti M.F., Zhang Z., Mortier E., Melchior A., Degeest G.,
RA   Geeraerts A., Ivarsson Y., Depoortere F., Coomans C., Vermeiren E.,
RA   Zimmermann P., David G.;
RT   "Syndecan-syntenin-ALIX regulates the biogenesis of exosomes.";
RL   Nat. Cell Biol. 14:677-685(2012).
RN   [27]
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.,
RA   Li X., Barkefors I., Thijssen V.L., Griffioen A.W., Claesson-Welsh L.;
RT   "Tetraspanin CD63 promotes vascular endothelial growth factor receptor
RT   2-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   [28]
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.,
RA   Kausar R., Jeong S.Y., Lee Y.S., Lee M.A.;
RT   "TIMP-1 modulates chemotaxis of human neural stem cells through CD63
RT   and integrin signalling.";
RL   Biochem. J. 459:565-576(2014).
RN   [29]
RP   CLEAVAGE OF INITIATOR METHIONINE [LARGE SCALE ANALYSIS], AND
RP   IDENTIFICATION 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.,
RA   Ayoub D., 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
CC       role in the activation of cellular signaling cascades. Plays a
CC       role in the activation of ITGB1 and integrin signaling, leading to
CC       the activation of AKT, FAK/PTK2 and MAP kinases. Promotes cell
CC       survival, reorganization of the actin cytoskeleton, cell adhesion,
CC       spreading and migration, via its role in the activation of AKT and
CC       FAK/PTK2. Plays a role in VEGFA signaling via its role in
CC       regulating the internalization of KDR/VEGFR2. Plays a role in
CC       intracellular vesicular transport processes, and is required for
CC       normal trafficking of the PMEL luminal domain that is essential
CC       for the development and maturation of melanocytes. Plays a role in
CC       the adhesion of leukocytes onto endothelial cells via its role in
CC       the regulation of SELP trafficking. May play a role in mast cell
CC       degranulation in response to Ms4a2/FceRI stimulation, but not in
CC       mast cell degranulation in response to other stimuli.
CC       {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
CC       ITGB1 (PubMed:16917503, PubMed:24635319). Interacts with CD9.
CC       Identified in a complex with CD9 and ITGB3 (PubMed:19640571).
CC       Interacts with PMEL (PubMed:21962903). Interacts with KDR/VEGFR2;
CC       identified in a complex with ITGB1 and KDR/VEGFR2 and is required
CC       to recruit KDR to ITGB1 complexes (PubMed:23632027). Interacts
CC       with SYT7 (By similarity). {ECO:0000250|UniProtKB:P41731,
CC       ECO:0000269|PubMed:16917503, ECO:0000269|PubMed:19640571,
CC       ECO:0000269|PubMed:21962903, ECO:0000269|PubMed:23632027,
CC       ECO:0000269|PubMed:24635319}.
CC   -!- INTERACTION:
CC       P04578:env (xeno); NbExp=4; IntAct=EBI-762053, EBI-6179711;
CC       P01033:TIMP1; NbExp=5; IntAct=EBI-762053, EBI-712536;
CC   -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000269|PubMed:15351990,
CC       ECO:0000269|PubMed:19640571, ECO:0000269|PubMed:23632027}; Multi-
CC       pass 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
CC       {ECO:0000269|PubMed:10793155, ECO:0000269|PubMed:23632027}; Multi-
CC       pass membrane protein {ECO:0000255}. Endosome, multivesicular body
CC       {ECO:0000269|PubMed:21962903}. Melanosome
CC       {ECO:0000269|PubMed:21962903}. Secreted, 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
CC       bodies of endothelial cells (PubMed:10793155). Located in platelet
CC       dense granules (PubMed:7682577). Detected in a subset of pre-
CC       melanosomes. Detected on intralumenal vesicles (ILVs) within
CC       multivesicular bodies (PubMed:21962903).
CC       {ECO:0000269|PubMed:10793155, ECO:0000269|PubMed:21962903,
CC       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         Note=Gene prediction based on EST data.;
CC   -!- TISSUE SPECIFICITY: Detected in platelets (at protein level).
CC       Dysplastic nevi, radial growth phase primary melanomas,
CC       hematopoietic cells, tissue macrophages.
CC       {ECO:0000269|PubMed:19640571}.
CC   -!- PTM: Palmitoylated at a low, basal level in unstimulated
CC       platelets. The level of palmitoylation increases when platelets
CC       are activated by thrombin (in vitro).
CC       {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).
CC       Hermansky-Pudlak syndrome (HPS) is a genetically heterogeneous,
CC       rare, autosomal recessive disorder characterized by oculocutaneous
CC       albinism, bleeding due to platelet storage pool deficiency, and
CC       lysosomal storage defects. This syndrome results from defects of
CC       diverse cytoplasmic organelles including melanosomes, platelet
CC       dense granules and lysosomes. Ceroid storage in the lungs is
CC       associated with pulmonary fibrosis, a common cause of premature
CC       death in individuals with HPS.
CC   -!- MISCELLANEOUS: This antigen is associated with early stages of
CC       melanoma tumor progression.
CC   -!- SIMILARITY: Belongs to the tetraspanin (TM4SF) family.
CC       {ECO:0000305}.
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   SMR; P08962; -.
DR   BioGrid; 107405; 38.
DR   CORUM; P08962; -.
DR   IntAct; P08962; 21.
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; -.
DR   iPTMnet; P08962; -.
DR   PhosphoSitePlus; P08962; -.
DR   SwissPalm; P08962; -.
DR   BioMuta; CD63; -.
DR   DMDM; 116026; -.
DR   EPD; P08962; -.
DR   jPOST; P08962; -.
DR   MaxQB; P08962; -.
DR   PaxDb; P08962; -.
DR   PeptideAtlas; P08962; -.
DR   PRIDE; P08962; -.
DR   ProteomicsDB; 52180; -.
DR   DNASU; 967; -.
DR   Ensembl; ENST00000257857; ENSP00000257857; ENSG00000135404. [P08962-1]
DR   Ensembl; ENST00000420846; ENSP00000393502; ENSG00000135404. [P08962-1]
DR   Ensembl; ENST00000546939; ENSP00000447356; ENSG00000135404. [P08962-3]
DR   Ensembl; ENST00000549117; ENSP00000447730; ENSG00000135404. [P08962-1]
DR   Ensembl; ENST00000550776; ENSP00000448091; ENSG00000135404. [P08962-3]
DR   Ensembl; ENST00000552692; ENSP00000449337; ENSG00000135404. [P08962-1]
DR   Ensembl; ENST00000552754; ENSP00000446807; ENSG00000135404. [P08962-2]
DR   GeneID; 967; -.
DR   KEGG; hsa:967; -.
DR   UCSC; uc001shn.5; human. [P08962-1]
DR   CTD; 967; -.
DR   DisGeNET; 967; -.
DR   GeneCards; CD63; -.
DR   HGNC; HGNC:1692; CD63.
DR   HPA; CAB026356; -.
DR   HPA; HPA010088; -.
DR   MIM; 155740; gene.
DR   neXtProt; NX_P08962; -.
DR   OpenTargets; ENSG00000135404; -.
DR   PharmGKB; PA26231; -.
DR   eggNOG; KOG3882; Eukaryota.
DR   eggNOG; ENOG4111IRY; LUCA.
DR   GeneTree; ENSGT00940000156832; -.
DR   HOGENOM; HOG000230651; -.
DR   InParanoid; P08962; -.
DR   KO; K06497; -.
DR   OMA; NDMISHY; -.
DR   OrthoDB; 1467737at2759; -.
DR   PhylomeDB; P08962; -.
DR   TreeFam; TF316345; -.
DR   Reactome; R-HSA-114608; Platelet degranulation.
DR   Reactome; R-HSA-6798695; Neutrophil degranulation.
DR   ChiTaRS; CD63; human.
DR   GeneWiki; CD63; -.
DR   GenomeRNAi; 967; -.
DR   PRO; PR:P08962; -.
DR   Proteomes; UP000005640; Chromosome 12.
DR   Bgee; ENSG00000135404; Expressed in 233 organ(s), highest expression level in upper lobe of lung.
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: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: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:0007166; P:cell surface receptor signaling pathway; IBA:GO_Central.
DR   GO; GO:0007160; P:cell-matrix adhesion; IMP:UniProtKB.
DR   GO; GO:0034613; P:cellular protein localization; IDA:MGI.
DR   GO; GO:0035646; P:endosome to melanosome transport; IMP:UniProtKB.
DR   GO; GO:0043312; P:neutrophil degranulation; TAS:Reactome.
DR   GO; GO:0048757; P:pigment granule maturation; IMP:UniProtKB.
DR   GO; GO:0002576; P:platelet degranulation; TAS:Reactome.
DR   GO; GO:0045807; P:positive regulation of endocytosis; IBA:GO_Central.
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; IPR000301; Tetraspanin.
DR   InterPro; IPR018499; Tetraspanin/Peripherin.
DR   InterPro; IPR018503; Tetraspanin_CS.
DR   InterPro; IPR008952; Tetraspanin_EC2_sf.
DR   Pfam; PF00335; Tetraspanin; 1.
DR   PIRSF; PIRSF002419; Tetraspanin; 1.
DR   PRINTS; PR00259; TMFOUR.
DR   SUPFAM; SSF48652; SSF48652; 1.
DR   PROSITE; PS00421; TM4_1; 1.
PE   1: Evidence at protein level;
DR   PRODOM; P08962.
DR   SWISS-2DPAGE; P08962.
KW   Alternative splicing; Cell membrane; Complete proteome;
KW   Direct protein sequencing; Endosome; Glycoprotein; Lipoprotein;
KW   Lysosome; Membrane; Palmitate; Protein transport; Reference proteome;
KW   Secreted; Transmembrane; Transmembrane helix; Transport.
FT   INIT_MET      1      1       Removed. {ECO:0000244|PubMed:25944712}.
FT   CHAIN         2    238       CD63 antigen.
FT                                /FTId=PRO_0000219216.
FT   TOPO_DOM      2     11       Cytoplasmic. {ECO:0000255}.
FT   TRANSMEM     12     32       Helical. {ECO:0000255}.
FT   TOPO_DOM     33     51       Extracellular. {ECO:0000255}.
FT   TRANSMEM     52     72       Helical. {ECO:0000255}.
FT   TOPO_DOM     73     81       Cytoplasmic. {ECO:0000255}.
FT   TRANSMEM     82    102       Helical. {ECO:0000255}.
FT   TOPO_DOM    103    203       Extracellular. {ECO:0000255}.
FT   TRANSMEM    204    224       Helical. {ECO:0000255}.
FT   TOPO_DOM    225    238       Cytoplasmic. {ECO:0000255}.
FT   MOTIF       234    238       Lysosomal targeting motif.
FT                                {ECO:0000250|UniProtKB:P41731}.
FT   CARBOHYD    130    130       N-linked (GlcNAc...) asparagine.
FT                                {ECO:0000269|PubMed:12754519,
FT                                ECO:0000269|PubMed:19159218}.
FT   CARBOHYD    150    150       N-linked (GlcNAc...) asparagine.
FT                                {ECO:0000255}.
FT   CARBOHYD    172    172       N-linked (GlcNAc...) asparagine.
FT                                {ECO:0000255}.
FT   VAR_SEQ       1     82       Missing (in isoform 3). {ECO:0000305}.
FT                                /FTId=VSP_046996.
FT   VAR_SEQ      23     45       Missing (in isoform 2).
FT                                {ECO:0000303|Ref.6}.
FT                                /FTId=VSP_045300.
FT   CONFLICT     36     36       Q -> E (in Ref. 13; AA sequence).
FT                                {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
//

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