CD63_MOUSE
ID CD63_MOUSE Reviewed; 238 AA.
AC P41731;
DT 01-NOV-1995, integrated into UniProtKB/Swiss-Prot.
DT 23-JAN-2007, sequence version 2.
DT 03-AUG-2022, entry version 167.
DE RecName: Full=CD63 antigen;
DE AltName: CD_antigen=CD63;
GN Name=Cd63;
OS Mus musculus (Mouse).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Mus; Mus.
OX NCBI_TaxID=10090;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RX PubMed=8148377; DOI=10.1016/0167-4781(94)90291-7;
RA Miyamoto M., Homma M., Hotta H.;
RT "Molecular cloning of the murine homologue of CD63/ME491 and detection of
RT its strong expression in the kidney and activated macrophages.";
RL Biochim. Biophys. Acta 1217:312-316(1994).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=FVB/N; TISSUE=Colon, and Mammary gland;
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 [3]
RP DISRUPTION PHENOTYPE, SUBCELLULAR LOCATION, AND FUNCTION.
RX PubMed=19075008; DOI=10.1128/mcb.01163-08;
RA Schroder J., Lullmann-Rauch R., Himmerkus N., Pleines I., Nieswandt B.,
RA Orinska Z., Koch-Nolte F., Schroder B., Bleich M., Saftig P.;
RT "Deficiency of the tetraspanin CD63 associated with kidney pathology but
RT normal lysosomal function.";
RL Mol. Cell. Biol. 29:1083-1094(2009).
RN [4]
RP GLYCOSYLATION [LARGE SCALE ANALYSIS] AT ASN-130.
RX PubMed=19349973; DOI=10.1038/nbt.1532;
RA Wollscheid B., Bausch-Fluck D., Henderson C., O'Brien R., Bibel M.,
RA Schiess R., Aebersold R., Watts J.D.;
RT "Mass-spectrometric identification and relative quantification of N-linked
RT cell surface glycoproteins.";
RL Nat. Biotechnol. 27:378-386(2009).
RN [5]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Kidney, Lung, and Spleen;
RX PubMed=21183079; DOI=10.1016/j.cell.2010.12.001;
RA Huttlin E.L., Jedrychowski M.P., Elias J.E., Goswami T., Rad R.,
RA Beausoleil S.A., Villen J., Haas W., Sowa M.E., Gygi S.P.;
RT "A tissue-specific atlas of mouse protein phosphorylation and expression.";
RL Cell 143:1174-1189(2010).
RN [6]
RP INTERACTION WITH SYT7, SUBCELLULAR LOCATION, AND MUTAGENESIS OF TYR-235.
RX PubMed=21041449; DOI=10.1083/jcb.201003021;
RA Flannery A.R., Czibener C., Andrews N.W.;
RT "Palmitoylation-dependent association with CD63 targets the Ca2+ sensor
RT synaptotagmin VII to lysosomes.";
RL J. Cell Biol. 191:599-613(2010).
RN [7]
RP DISRUPTION PHENOTYPE, AND FUNCTION.
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 [8]
RP FUNCTION IN MELANOCYTE DEVELOPMENT, AND DISRUPTION PHENOTYPE.
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 [9]
RP FUNCTION, AND DISRUPTION PHENOTYPE.
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 [10]
RP FUNCTION, DISRUPTION PHENOTYPE, AND SUBCELLULAR LOCATION.
RX PubMed=23945142; DOI=10.4049/jimmunol.1202323;
RA Kraft S., Jouvin M.H., Kulkarni N., Kissing S., Morgan E.S., Dvorak A.M.,
RA Schroder B., Saftig P., Kinet J.P.;
RT "The tetraspanin CD63 is required for efficient IgE-mediated mast cell
RT degranulation and anaphylaxis.";
RL J. Immunol. 191:2871-2878(2013).
RN [11]
RP SUBCELLULAR LOCATION.
RC TISSUE=Macrophage;
RX PubMed=26109643; DOI=10.4049/jimmunol.1402894;
RA Athman J.J., Wang Y., McDonald D.J., Boom W.H., Harding C.V., Wearsch P.A.;
RT "Bacterial membrane vesicles mediate the release of Mycobacterium
RT tuberculosis lipoglycans and lipoproteins from infected macrophages.";
RL J. Immunol. 195:1044-1053(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:19075008, ECO:0000269|PubMed:21803846,
CC ECO:0000269|PubMed:21962903, ECO:0000269|PubMed:23632027,
CC ECO:0000269|PubMed:23945142}.
CC -!- SUBUNIT: Interacts with TIMP1 and ITGB1 and recruits TIMP1 to ITGB1.
CC Interacts with CD9. Identified in a complex with CD9 and ITGB3.
CC Interacts with PMEL. Interacts with KDR/VEGFR2; identified in a complex
CC with ITGB1 and KDR/VEGFR2 and is required to recruit KDR to ITGB1
CC complexes (By similarity). Interacts with SYT7 (PubMed:21041449).
CC {ECO:0000250, ECO:0000269|PubMed:21041449}.
CC -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000250|UniProtKB:P08962};
CC Multi-pass membrane protein {ECO:0000255}. Lysosome membrane
CC {ECO:0000269|PubMed:19075008, ECO:0000269|PubMed:21041449,
CC ECO:0000269|PubMed:23945142}; Multi-pass membrane protein
CC {ECO:0000255}. Late endosome membrane {ECO:0000269|PubMed:23945142};
CC Multi-pass membrane protein {ECO:0000255}. Endosome, multivesicular
CC body {ECO:0000250|UniProtKB:P08962}. Melanosome
CC {ECO:0000250|UniProtKB:P08962}. Secreted, extracellular exosome
CC {ECO:0000269|PubMed:26109643}. Cell surface
CC {ECO:0000250|UniProtKB:P08962}. Note=Also found in Weibel-Palade bodies
CC of endothelial cells. Located in platelet dense granules. Detected in a
CC subset of pre-melanosomes. Detected on intralumenal vesicles (ILVs)
CC within multivesicular bodies. {ECO:0000250|UniProtKB:P08962}.
CC -!- TISSUE SPECIFICITY: Ubiquitous. Strongly expressed in kidney. Detected
CC in spleen, bone marrow, peripheral blood mononuclear cells and
CC macrophages.
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) (By similarity). {ECO:0000250}.
CC -!- DISRUPTION PHENOTYPE: No visible phenotype. Mutant mice are viable and
CC fertile, but display impaired water homeostasis, with increased urinary
CC flow, increased water intake, reduced urine osmolality and increased
CC fecal water content. Mice display inclusions in the principal cells in
CC the renal collecting duct (PubMed:19075008). Mutant mice display
CC variable graying of their coat color and a dramatic reduction in the
CC number of melanosomes in the retinal pigment epithelium
CC (PubMed:21962903). According to PubMed:21803846, mutant mice display a
CC defect in the Selp-dependent attachment of leukocytes to endothelial
CC cells. According to PubMed:23945142, mast cells from mutant mice show
CC decreased degranulation and decreased release of TNF in response to
CC Ms4a2/FceRI stimulation, but no difference in mast cell degranulation
CC in response to other stimuli and no change in the release of IL6 and
CC leukotriene C4. {ECO:0000269|PubMed:19075008,
CC ECO:0000269|PubMed:21803846, ECO:0000269|PubMed:21962903,
CC ECO:0000269|PubMed:23632027, ECO:0000269|PubMed:23945142}.
CC -!- SIMILARITY: Belongs to the tetraspanin (TM4SF) family. {ECO:0000305}.
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DR EMBL; D16432; BAA03904.1; -; mRNA.
DR EMBL; BC008108; AAH08108.1; -; mRNA.
DR EMBL; BC012212; AAH12212.1; -; mRNA.
DR EMBL; BC083161; AAH83161.1; -; mRNA.
DR CCDS; CCDS24297.1; -.
DR PIR; S43511; S43511.
DR RefSeq; NP_001036045.1; NM_001042580.1.
DR RefSeq; NP_001269895.1; NM_001282966.1.
DR RefSeq; NP_031679.1; NM_007653.3.
DR AlphaFoldDB; P41731; -.
DR SMR; P41731; -.
DR BioGRID; 198606; 8.
DR IntAct; P41731; 2.
DR STRING; 10090.ENSMUSP00000100862; -.
DR GlyGen; P41731; 4 sites.
DR iPTMnet; P41731; -.
DR PhosphoSitePlus; P41731; -.
DR SwissPalm; P41731; -.
DR jPOST; P41731; -.
DR PaxDb; P41731; -.
DR PeptideAtlas; P41731; -.
DR PRIDE; P41731; -.
DR ProteomicsDB; 280027; -.
DR Antibodypedia; 2770; 2071 antibodies from 48 providers.
DR DNASU; 12512; -.
DR Ensembl; ENSMUST00000026407; ENSMUSP00000026407; ENSMUSG00000025351.
DR Ensembl; ENSMUST00000105229; ENSMUSP00000100862; ENSMUSG00000025351.
DR Ensembl; ENSMUST00000219317; ENSMUSP00000151313; ENSMUSG00000025351.
DR GeneID; 12512; -.
DR KEGG; mmu:12512; -.
DR UCSC; uc007hou.1; mouse.
DR CTD; 967; -.
DR MGI; MGI:99529; Cd63.
DR VEuPathDB; HostDB:ENSMUSG00000025351; -.
DR eggNOG; KOG3882; Eukaryota.
DR GeneTree; ENSGT00940000156832; -.
DR HOGENOM; CLU_055524_6_1_1; -.
DR InParanoid; P41731; -.
DR OMA; MQEDFKC; -.
DR OrthoDB; 1467737at2759; -.
DR PhylomeDB; P41731; -.
DR TreeFam; TF316345; -.
DR Reactome; R-MMU-114608; Platelet degranulation.
DR Reactome; R-MMU-6798695; Neutrophil degranulation.
DR BioGRID-ORCS; 12512; 1 hit in 77 CRISPR screens.
DR ChiTaRS; Cd63; mouse.
DR PRO; PR:P41731; -.
DR Proteomes; UP000000589; Chromosome 10.
DR RNAct; P41731; protein.
DR Bgee; ENSMUSG00000025351; Expressed in right kidney and 68 other tissues.
DR ExpressionAtlas; P41731; baseline and differential.
DR GO; GO:0009986; C:cell surface; ISO:MGI.
DR GO; GO:0005737; C:cytoplasm; ISO:MGI.
DR GO; GO:0031904; C:endosome lumen; ISO:MGI.
DR GO; GO:0010008; C:endosome membrane; ISO:MGI.
DR GO; GO:0070062; C:extracellular exosome; ISO:MGI.
DR GO; GO:0005615; C:extracellular space; ISO:MGI.
DR GO; GO:0005887; C:integral component of plasma membrane; IBA:GO_Central.
DR GO; GO:0043231; C:intracellular membrane-bounded organelle; ISO:MGI.
DR GO; GO:0031226; C:intrinsic component of plasma membrane; ISS:UniProtKB.
DR GO; GO:0005770; C:late endosome; IDA:MGI.
DR GO; GO:0031902; C:late endosome membrane; ISS:UniProtKB.
DR GO; GO:0005765; C:lysosomal membrane; ISS:UniProtKB.
DR GO; GO:0005764; C:lysosome; IDA:MGI.
DR GO; GO:0042470; C:melanosome; IEA:UniProtKB-SubCell.
DR GO; GO:0032585; C:multivesicular body membrane; ISS:UniProtKB.
DR GO; GO:0097487; C:multivesicular body, internal vesicle; ISS:UniProtKB.
DR GO; GO:0005654; C:nucleoplasm; ISO:MGI.
DR GO; GO:0005886; C:plasma membrane; ISO:MGI.
DR GO; GO:0032991; C:protein-containing complex; ISO:MGI.
DR GO; GO:0044877; F:protein-containing complex binding; ISO:MGI.
DR GO; GO:0016477; P:cell migration; ISS:UniProtKB.
DR GO; GO:0007160; P:cell-matrix adhesion; ISS:UniProtKB.
DR GO; GO:0035646; P:endosome to melanosome transport; ISS:UniProtKB.
DR GO; GO:0030855; P:epithelial cell differentiation; ISO:MGI.
DR GO; GO:0010633; P:negative regulation of epithelial cell migration; ISO:MGI.
DR GO; GO:0050931; P:pigment cell differentiation; IMP:UniProtKB.
DR GO; GO:0048757; P:pigment granule maturation; ISS:UniProtKB.
DR GO; GO:0043473; P:pigmentation; IMP:UniProtKB.
DR GO; GO:0045785; P:positive regulation of cell adhesion; ISO:MGI.
DR GO; GO:0045807; P:positive regulation of endocytosis; ISO:MGI.
DR GO; GO:2001046; P:positive regulation of integrin-mediated signaling pathway; ISS:UniProtKB.
DR GO; GO:0002092; P:positive regulation of receptor internalization; ISS:UniProtKB.
DR GO; GO:0008104; P:protein localization; ISO:MGI.
DR GO; GO:0015031; P:protein transport; IEA:UniProtKB-KW.
DR GO; GO:1901379; P:regulation of potassium ion transmembrane transport; ISO: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 Cell membrane; Endosome; Glycoprotein; Lipoprotein; Lysosome; Membrane;
KW Palmitate; Protein transport; Reference proteome; Secreted; Transmembrane;
KW Transmembrane helix; Transport.
FT CHAIN 1..238
FT /note="CD63 antigen"
FT /id="PRO_0000219217"
FT TOPO_DOM 1..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:0000269|PubMed:21041449"
FT CARBOHYD 116
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 130
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000269|PubMed:19349973"
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 MUTAGEN 235
FT /note="Y->A: Abolishes localization to lysosomes."
FT /evidence="ECO:0000269|PubMed:21041449"
SQ SEQUENCE 238 AA; 25767 MW; B57E47B31E13EED8 CRC64;
MAVEGGMKCV KFLLYVLLLA FCACAVGLIA IGVAVQVVLK QAITHETTAG SLLPVVIIAV
GAFLFLVAFV GCCGACKENY CLMITFAIFL SLIMLVEVAV AIAGYVFRDQ VKSEFNKSFQ
QQMQNYLKDN KTATILDKLQ KENNCCGASN YTDWENIPGM AKDRVPDSCC INITVGCGND
FKESTIHTQG CVETIAIWLR KNILLVAAAA LGIAFVEVLG IIFSCCLVKS IRSGYEVM
