Protein detail

CD81

CD81 antigen (26 kDa cell surface protein TAPA-1) (Target of the antiproliferative antibody 1) (Tetraspanin-28) (Tspan-28) (CD antigen CD81)

Entry name CD81	UniProt ID P60033	EVMP confidence score 0.88
Supporting publications (n) 305	Transmembrane count 4	Protein classification CD markersDisease related genesHuman disease related genesPlasma proteinsPotential drug targetsPredicted 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

CD81 antigen (26 kDa cell surface protein TAPA-1) (Target of the antiproliferative antibody 1) (Tetraspanin-28) (Tspan-28) (CD antigen CD81)

Protein Class (7)

CD markersDisease related genesHuman disease related genesPlasma proteinsPotential drug targetsPredicted membrane proteinsTransporters

Protein Function (5)

CD markers
Potential drug targets
Human disease related genes:Immune system diseases:Primary immunodeficiency
Transporters:Accessory Factors Involved in Transport
Disease related genes

Transmembrane

13..33; Helical; 64..84; Helical; 90..112; Helical; 202..224; Helical

Transmembrane Count

Ensembl

ENSG00000110651

Entrez Gene Symbol

CD81

Gene Synonym (3)

TAPA-1TAPA1TSPAN28

Gene Description

CD81 molecule

Chromosome

Position

2376177-2397802

Supporting publications (n)

305

EVMP confidence score

0.88

Fluorescence & Localization7

Tissue Specificheart muscleCell SpecificCardiomyocytesBlood Cell SpecificneutrophilBlood Lineage SpecificgranulocytesSecretome LocationIntracellular and membraneSecretome FunctionTransport

Function & Pathway8

Protein Function (5)

CD markers
Potential drug targets
Human disease related genes:Immune system diseases:Primary immunodeficiency
Transporters:Accessory Factors Involved in Transport
Disease related genes

Cellular Component (9)

Molecular Function (7)

Biological Process (3)

KEGG (4)

Reactome (4)

Canonical Pathways

M13 Pid erbb4 pathway

Mediation Categories (4)

Adhesion and uptake mediationFusion and delivery mediationImmune mediationReceptor-signaling mediation

Relations & Evidence44

Ligand-Receptor Signaling (41)

41 records.

Category	Parent	Database	Transmitter	Receiver	Secreted	Plasma Membrane (Transmembrane)	Plasma Membrane (Peripheral)
intracellular	intracellular	LOCATE	No	No	No	Yes	No
intracellular	intracellular	ComPPI	No	No	No	Yes	No
intracellular	intracellular	GO_Intercell	No	No	No	Yes	No
intracellular	intracellular	OmniPath	No	No	No	Yes	No
cell_surface_ligand	cell_surface_ligand	Baccin2019	Yes	No	No	Yes	No
cell_surface_ligand	cell_surface_ligand	OmniPath	Yes	No	No	Yes	No
cell_adhesion	cell_adhesion	Cellinker	Yes	Yes	No	Yes	No
adhesion	adhesion	OmniPath	Yes	Yes	No	Yes	No
cell_adhesion	cell_adhesion	OmniPath	Yes	Yes	No	Yes	No
transmembrane	transmembrane	UniProt_location	No	No	No	Yes	No

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Protein Complex Composition (2)

2 records.

Component Name	Component Gene Symbols	Component UniProt ID	Stoichiometry	Database	Database IDs	References
	CD81 CTSC	P53634 P60033	0:0	Havugimana2012	Havugimana2012:C_97
	CD81	P60033	2	PDB	PDB:5dfvPDB:6ejmPDB:3x0ePDB:5m3dPDB:5m3tPDB:5m2cPDB:6ejgPDB:5m33PDB:1g8qPDB:6ek2PDB:1iv5PDB:6u9sPDB:5m4r

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 & Domains9

Sequences

Length

236

Mass

25,809

Sequence

MGVEGCTKCIKYLLFVFNFVFWLAGGVILGVALWLRHDPQTTNLLYLELGDKPAPNTFYVGIYILIAVGAVMMFVGFLGCYGAIQESQCLLGTFFTCLVILFACEVAAGIWGFVNKDQIAKDVKQFYDQALQQAVVDDDANNAKAVVKTFHETLDCCGSSTLTALTTSVLKNNLCPSGSNIISNLFKEDCHQKIDDLFSGKLYLIGIAAIVVAVIMIFEMILSMVLCCGIRNSSVY

3D Structural Models

Helix

10..36; 57..80; 81..84; 113..115; 116..136; 141..154; 163..165; 166..171; 172..174; 181..185; 190..199; 202..230

Beta Strand

158..160

3D Structure

Electron microscopy (1); X-ray crystallography (15)

Domain & Motif Annotations

Domain (CC)

Binds cholesterol in a cavity lined by the transmembrane spans.

Protein Families

Tetraspanin (TM4SF) family

Sequence Similarities

Belongs to the tetraspanin (TM4SF) family.

Clinical Relevance4

Antibody (2)

CAB002507 HPA007234

Interaction Protein (3)

ENSG00000010278ENSG00000078369ENSG00000134247

Interaction Count

Interaction Dataset

biogrid_opencell

Supporting Publications305

PMID	Title	Abstract
12147373	Malignant effusions and immunogenic tumour-derived exosomes.	Exosomes from patients with melanoma deliver Mart1 tumour antigens to dendritic cells derived from monocytes (MD-DCs) for cross presentation to clones of cytotoxic T lymphocytes specific to Mart1.
14633944	Intestinal epithelial exosomes carry MHC class II/peptides able to inform the immune system in mice.	A33 antigen, an Ig-like molecule highly specific for intestinal epithelial cells, was enriched in exosomes and was also found in mice mesenteric lymph nodes, suggesting exosome migration towards the gut associated lymphoid tissues. CONCLUSIONS: Epithelial exosomes are antigen presenting vesicles bearing MHC class II/peptide complexes that prime for an immunogenic rather than tolerogenic response in the context of a systemic challenge. In contrast, exosomes obtained after incubation with IFN-gamma (EXO-hOVA-IFN), bearing abundant MHC class II/OVA complexes, induced a specific humoral immune response. RESULTS: MODE K epithelial exosomes displayed major histocompatibility complex (MHC) class I and class II (upregulated by IFN-gamma) molecules and tetraspan proteins (CD9, CD81, CD82) potentially involved in the binding to target cells.
15284116	Endocytosis, intracellular sorting, and processing of exosomes by dendritic cells.	Targeting of exosomes to DCs is mediated via milk fat globule (MFG)-E8/lactadherin, CD11a, CD54, phosphatidylserine, and the tetraspanins CD9 and CD81 on the exosome and alpha(v)/beta(3) integrin, and CD11a and CD54 on the DCs.
15368299	Association of hepatitis C virus envelope proteins with exosomes.	Instead, when huCD81 is present, a fraction of HCV envelope proteins passes through the Golgi apparatus, matures acquiring complex sugars and is found extracellularly associated with exosomes. We propose that the HCV-CD81 complex leaves cells in the form of exosomes, circulates in this form and exploits the fusogenic capabilities of these vesicles to infect cells even in the presence of neutralizing antibodies.
16023874	Characterization of exosome subpopulations from RBL-2H3 cells using fluorescent lipids.	CD63, MHC II, and CD81-containing exosomes accounted for 47%, 32%, and 21%, respectively, of total exosomes. Sorting of subpopulations indicated that the MHC-II containing exosomes were enriched in Bodipy-PC, whereas tetraspanin(CD 63 or CD81)-containing exosomes are essentially labeled with Bodipy-Cer and Bodipy-PC.
17046995	TfR2 localizes in lipid raft domains and is released in exosomes to activate signal transduction along the MAPK pathway.	Co-localization of TfR2 with CD81, a raft tetraspanin exported through exosomes, prompted us to investigate exosomes released by HepG2 and K562 cells into culture medium. In conclusion, the present study indicates that TfR2 localizes in LDTI microdomains, where it promotes cell signalling, and is exported out of the cells through the exosome pathway, where it acts as an intercellular messenger.
17407154	The transferrin receptor and the tetraspanin web molecules CD9, CD81, and CD9P-1 are differentially sorted into exosomes after TPA treatment of K562 cells.	However, CD9P-1 could be targeted to exosomes in the absence of CD81 and of another tetraspanin, CD9. TPA increased targeting of CD81 and CD9P-1 into exosomes but strongly reduced the localization of the TfR in these vesicles. The targeting of CD9 into exosomes did not require palmitoylation of the protein. Using this model we have shown that a fraction of CD81 and CD9P-1 in exosomes comes from a surface pool and that these molecules remain associated in exosomes.
17484880	T84-intestinal epithelial exosomes bear MHC class II/peptide complexes potentiating antigen presentation by dendritic cells.	RESULTS: T84-derived exosomes, enriched in CD9, CD81, CD82, and A33 antigen, were capable of binding specifically human serum albumin (HSA) 64-76 peptide on HLA-DR4 molecules and of interacting preferentially with DCs.
17868797	B cell-derived exosomes can present allergen peptides and activate allergen-specific T cells to proliferate and produce TH2-like cytokines.	Exosomes from antigen-presenting cells carry immunorelevant molecules like MHC class I and II and costimulatory molecules and thus are suggested to have a role in immune modulation. RESULTS: The exosomes had a phenotype typical of B cell-derived exosomes with expression of MHC, costimulatory molecules like CD86, tetraspanin proteins such as CD81, and CD19.
17894858	Platelet-derived exosomes induce endothelial cell apoptosis through peroxynitrite generation: experimental evidence for a novel mechanism of septic vascular dysfunction.	Endothelial cells exposed to the exosomes underwent apoptosis and caspase-3 activation, which were inhibited by NO synthase inhibitors or by a superoxide dismutase mimetic and totally blocked by urate (1 mM), suggesting a role for the peroxynitrite radical. RESULTS: Size, morphology, high exposure of the tetraspanins CD9, CD63, and CD81, together with low phosphatidylserine, showed that platelets exposed to NONOate and LPS, but not to TNF-alpha or thrombin, generate microparticles similar to those recovered from septic patients, and characterize them as exosomes.

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