Protein detail

CD63

CD63 antigen (Granulophysin) (Lysosomal-associated membrane protein 3) (LAMP-3) (Lysosome integral membrane protein 1) (Limp1) (Melanoma-associated antigen ME491) (OMA81H) (Ocular melanoma-associated antigen) (Tetraspanin-30) (Tspan-30) (CD antigen CD63)

Entry name CD63	UniProt ID P08962	EVMP confidence score 0.63
Supporting publications (n) 765	Transmembrane count 4	Protein classification CD markersPlasma proteinsPredicted membrane proteinsTransporters

EVMP confidence score

Annotation confidence score; open for threshold definitions.

Extremely high >= 0.85High >= 0.70Medium >= 0.55Low >= 0.40

Basic Information13

Protein Names

Protein Class (4)

CD markersPlasma proteinsPredicted membrane proteinsTransporters

Protein Function (2)

CD markers
Transporters:Accessory Factors Involved in Transport

Transmembrane

12..32; Helical; 52..72; Helical; 82..102; Helical; 204..224; Helical

Transmembrane Count

Ensembl

ENSG00000135404

Entrez Gene Symbol

CD63

Gene Synonym (3)

ME491MLA1TSPAN30

Gene Description

CD63 molecule

Chromosome

Position

55725323-55729707

Supporting publications (n)

765

EVMP confidence score

0.63

Fluorescence & Localization4

Tissue Specificblood vesselCell SpecificNeutrophil progenitorsSingle-Nuclei Brain Specificendothelial cell

Function & Pathway7

Protein Function (2)

CD markers
Transporters:Accessory Factors Involved in Transport

Cellular Component (15)

Page 1 of 2

Molecular Function

GO:0005515 protein binding

Biological Process (3)

KEGG (3)

Reactome (5)

Mediation Categories (3)

Adhesion and uptake mediationFusion and delivery mediationImmune mediation

Relations & Evidence49

Ligand-Receptor Signaling (47)

47 records.

Category	Parent	Database	Transmitter	Receiver	Secreted	Plasma Membrane (Transmembrane)	Plasma Membrane (Peripheral)
plasma_membrane	plasma_membrane	Cellinker	No	No	Yes	Yes	No
plasma_membrane	plasma_membrane	OmniPath	No	No	Yes	Yes	No
plasma_membrane_transmembrane	plasma_membrane_transmembrane	CSPA	No	No	Yes	Yes	No
plasma_membrane_transmembrane	plasma_membrane_transmembrane	HPMR	No	No	Yes	Yes	No
plasma_membrane_transmembrane	plasma_membrane_transmembrane	OmniPath	No	No	Yes	Yes	No
secreted	secreted	UniProt_keyword	No	No	Yes	Yes	No
secreted	secreted	UniProt_location	No	No	Yes	Yes	No
secreted	secreted	OmniPath	No	No	Yes	Yes	No
cell_surface	cell_surface	Surfaceome	No	No	Yes	Yes	No
cell_surface	cell_surface	connectomeDB2020	No	No	Yes	Yes	No

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Protein Complex Composition (1)

1 record.

Component Name	Component Gene Symbols	Component UniProt ID	Stoichiometry	Database	Database IDs	References
HT_DM_Cluster25	ARL6IP5 ATP5F1A ATP5F1D ATP5ME ATP5MF ATP5MG ATP5MGL ATP5PB ATP5PO CD63 ELOVL1 ELOVL7 PRAF2 RTN1 RTN2 RTN3 RTN4 TSPAN6	A1L3X0 O43657 O60831 O75298 O75915 O75964 O95197 P08962 P24539 P25705 P30049 P48047 P56134 P56385 Q16799 Q7Z4Y8 Q9BW60 Q9NQC3	1:1:1:1:1:1:1:1:1:1:1:1:1:1:1:1:1:1	Compleat	Compleat:HC3353	22036573

Isolation & Detection Technology (1)

1 record.

EV Isolation Method	Detection Method	Number of References	References
	Mass spectrometry [LTQ-FT Ultra]Mass spectrometry	0

Sequence, Structure & Domains8

Sequences

Length

238

Mass

25,637

Sequence

MAVEGGMKCVKFLLYVLLLAFCACAVGLIAVGVGAQLVLSQTIIQGATPGSLLPVVIIAVGVFLFLVAFVGCCGACKENYCLMITFAIFLSLIMLVEVAAAIAGYVFRDKVMSEFNNNFRQQMENYPKNNHTASILDRMQADFKCCGAANYTDWEKIPSMSKNRVPDSCCINVTVGCGINFNEKAIHKEGCVEKIGGWLRKNVLVVAAAALGIAFVEVLGIVFACCLVKSIRSGYEVM

Alternative Products

Event=Alternative splicing; Named isoforms=3; Name=1; IsoId=P08962-1; Sequence=Displayed; Name=2; IsoId=P08962-2; Sequence=VSP_045300; Name=3; IsoId=P08962-3; Sequence=VSP_046996

Alternative Sequence

1..82; Missing (in isoform 3); 23..45; Missing (in isoform 2)

Domain & Motif Annotations

Motif

234..238; Lysosomal targeting motif

Protein Families

Tetraspanin (TM4SF) family

Sequence Similarities

Belongs to the tetraspanin (TM4SF) family.

Clinical Relevance5

Drugs (2)

NONSTEROIDAL ANTIINFLAMMATORY DRUG COMPOUND 6B [PMID: 22749870]

Antibody (3)

HPA010088 CAB026356 HPA073506

Interaction Protein (2)

ENSG00000102265ENSG00000150093

Interaction Count

Interaction Dataset

intact_biogrid

Supporting Publications741

PMID	Title	Abstract
22895844	Exosomes secreted from human colorectal cancer cell lines contain mRNAs, microRNAs and natural antisense RNAs, that can transfer into the human hepatoma HepG2 and lung cancer A549 cell lines.	CD81 was detected in exosomes secreted from the three CRC cell lines. Furthermore, PKH67-labeled exosomes derived from the CRC cell lines were taken up into HepG2 and A549 cells. In the present study, we investigated the tetraspanin family proteins CD63, CD9 and CD81 as useful collection markers of exosomes derived from the three colorectal cancer (CRC) cell lines HCT-15, SW480 and WiDr. This result indicates that CD81 can be a collection marker of exosomes derived from the three CRC cell lines. When the RNA species within exosomes derived from the three CRC cell lines were examined, the mRNAs of housekeeping genes such as ACTB and GAPDH, the microRNAs such as miR-21, miR-192 and miR-221, and the natural antisense RNAs of LRRC24, MDM2 and CDKN1A genes, were detected.
22921594	Imaging exosome transfer from breast cancer cells to stroma at metastatic sites in orthotopic nude-mouse models.	In order to image the fate of cancer-cell-derived exosomes in orthotopic nude mouse models of breast cancer, we used green fluorescent protein (GFP)-tagged CD63, which is a general marker of exosomes.
22998595	Hypoxic enhancement of exosome release by breast cancer cells.	Exosomes were isolated from conditioned media and quantitated by nanoparticle tracking analysis (NTA) and immunoblotting for the exosomal protein CD63 in order to assess the impact of hypoxia on exosome release. RESULTS: Exposure of three different breast cancer cell lines to moderate (1% O2) and severe (0.1% O2) hypoxia resulted in significant increases in the number of exosomes present in the conditioned media as determined by NTA and CD63 immunoblotting.
23085511	Mechanism of TNF-α autocrine effects in hypoxic cardiomyocytes: initiated by hypoxia inducible factor 1α, presented by exosomes.	Exosomes (vesicles mediating a non-classical route of protein secretion) in supernatants from hypoxic cardiomyocytes were identified by an anti-CD63 antibody in Western blot and observed by electron microscopy. Results of this study indicate that under hypoxia, HIF-1α initiates expression of TNF-α, mediated by exosomes in cardiomyocytes. The presence of TNF-α within exosomes precipitated from supernatants of hypoxic cardiomyocytes was verified by immunoelectron microscopy and immunoblotting.
23107341	Immunomodulatory molecules are released from the first trimester and term placenta via exosomes.	Confocal microscopy of placental sections revealed intracellular co-localization of B7-H1 with CD63, suggesting that B7-H1 associates with subcellular vesicles that give rise to exosomes. Finally, culture of purified trophoblast cells in the presence or absence of EGF suggested that despite the absence of HLA-G5 association with term explant-derived exosomes, it is present in exosomes secreted from mononuclear cytotrophoblast cells. First trimester and term placental explants were then cultured for 24 h. B7H-1 (CD274), B7-H3 (CD276) and HLA-G5 were abundant in pelleted supernatants of these cultures that contained microparticles and exosomes; the latter, however, was observed only in first trimester pellets and was nearly undetectable in term explant-derived pellets. Further, differentiation of cytotrophoblast cells reduced the presence of HLA-G5 in secreted exosomes. Here we investigate the possibility that exosomes secreted from the first trimester and term placenta carry HLA-G and B7 family immunomodulators.
23230278	Two distinct populations of exosomes are released from LIM1863 colon carcinoma cell-derived organoids.	Additionally, we report for the first time in any extracellular vesicle study the colocalization of EpCAM, claudin-7, and CD44 in EpCAM-Exos. Here we describe the isolation, via sequential immunocapture using anti-A33- and anti-EpCAM-coupled magnetic beads, of two distinct populations of exosomes released from organoids derived from human colon carcinoma cell line LIM1863. Our observations are consistent with EpCAM- and A33-Exos being released from the apical and basolateral surfaces, respectively, and the EpCAM-Exos proteome profile with widely published stereotypical exosomes. The exosome populations (A33-Exos and EpCAM-Exos) could not be distinguished via electron microscopy and contained stereotypical exosome markers such as TSG101, Alix, and HSP70.
23318173	Cardiac progenitor-derived exosomes protect ischemic myocardium from acute ischemia/reperfusion injury.	Exosomes were purified from conditional medium, and confirmed by electron micrograph and Western blot using CD63 as a marker.
23402739	Detection of exosomal biomarker by electric field-induced release and measurement (EFIRM).	We confirmed in vivo that H460-CD63-GFP shed exosomes were transported to blood and saliva. We tested the hypothesis that the lung cancer cell line, H460 stably transfected with hCD63-GFP, would shed hCD63-GFP expressing exosomes that could be detected in serum and saliva.
23516492	Endometrial exosomes/microvesicles in the uterine microenvironment: a new paradigm for embryo-endometrial cross talk at implantation.	Immunostaining demonstrated that the tetraspanins, CD9 and CD63 used as cell surface markers of exosomes are present on the apical surfaces of endometrial epithelial cells in tissue sections taken across the menstrual cycle: CD63 showed cyclical regulation.
23521563	First identification of Ewing's sarcoma-derived extracellular vesicles and exploration of their biological and potential diagnostic implications.	ES cell line-derived EV shave been isolated by ultracentrifugation and analysed by flow-cytometric assessment of the exosome-associated proteins CD63 and CD81 as well as by electron microscopy.

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