Protein detail

CD9

CD9 antigen (5H9 antigen) (Cell growth-inhibiting gene 2 protein) (Leukocyte antigen MIC3) (Motility-related protein) (MRP-1) (Tetraspanin-29) (Tspan-29) (p24) (CD antigen CD9)

Entry name CD9	UniProt ID P21926	EVMP confidence score 0.88
Supporting publications (n) 424	Transmembrane count 4	Protein classification Cancer-related genesCD 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

CD9 antigen (5H9 antigen) (Cell growth-inhibiting gene 2 protein) (Leukocyte antigen MIC3) (Motility-related protein) (MRP-1) (Tetraspanin-29) (Tspan-29) (p24) (CD antigen CD9)

Protein Class (5)

Cancer-related genesCD markersPlasma proteinsPredicted membrane proteinsTransporters

Protein Function (3)

Cancer-related genes:Candidate cancer biomarkers
CD markers
Transporters:Accessory Factors Involved in Transport

Transmembrane

13..33; Helical; 56..76; Helical; 88..111; Helical; 196..221; Helical

Transmembrane Count

Ensembl

ENSG00000010278

Entrez Gene Symbol

CD9

Gene Synonym (5)

BA2MIC3MRP-1P24TSPAN29

Gene Description

CD9 molecule

Chromosome

Position

6199715-6238271

Supporting publications (n)

424

EVMP confidence score

0.88

Fluorescence & Localization1

Function & Pathway7

Protein Function (3)

Cancer-related genes:Candidate cancer biomarkers
CD markers
Transporters:Accessory Factors Involved in Transport

Cellular Component (11)

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Molecular Function (2)

Biological Process (3)

KEGG (2)

Reactome (10)

Mediation Categories (4)

Adhesion and uptake mediationClinical-translation mediationFusion and delivery mediationImmune mediation

Relations & Evidence41

Ligand-Receptor Signaling (32)

32 records.

Category	Parent	Database	Transmitter	Receiver	Secreted	Plasma Membrane (Transmembrane)	Plasma Membrane (Peripheral)
transmembrane	transmembrane	OmniPath	No	No	Yes	No	No
plasma_membrane	plasma_membrane	UniProt_location	No	No	Yes	No	No
plasma_membrane	plasma_membrane	Cellinker	No	No	Yes	No	No
plasma_membrane	plasma_membrane	OmniPath	No	No	Yes	No	No
secreted	secreted	UniProt_keyword	No	No	Yes	No	No
secreted	secreted	UniProt_location	No	No	Yes	No	No
secreted	secreted	OmniPath	No	No	Yes	No	No
cell_surface	cell_surface	Surfaceome	No	No	Yes	No	No
cell_surface	cell_surface	connectomeDB2020	No	No	Yes	No	No
cell_surface	cell_surface	Baccin2019	No	No	Yes	No	No

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Protein Complex Composition (8)

8 records.

Component Gene Symbols	Component UniProt ID	Stoichiometry	Database	Database IDs
ASAP3 CD96 CER1 HSPA1B LDB3	O75112 O95813 P0DMV9 P40200 Q8TDY4	0:0:0:0:0	hu.MAP2
CD96 HSPA1A LDB3	O75112 P0DMV8 P40200	0:0:0	hu.MAP
CD96 HSPA1B LDB3	O75112 P0DMV9 P40200	0:0:0	hu.MAP
AFG2B CD96 HSPA1B LDB3	O75112 P0DMV9 P40200 Q9BVQ7	0:0:0:0	hu.MAP2
CCNB2 CD96 CRHBP NAA20 POGLUT1 SQSTM1 TNIP1	O95067 P24387 P40200 P61599 Q13501 Q15025 Q8NBL1	0:0:0:0:0:0:0	hu.MAP2
CD99	P14209	2	PDB	PDB:7sfx
CD9	P21926	4	PDB	PDB:6z20PDB:6rlrPDB:6rlo
CD93	Q9NPY3	4	PDB	PDB:8ivd

Isolation & Detection Technology (1)

1 record.

EV Isolation Method	Detection Method	Number of References	References
Differential UltracentrifugationSize Exclusion Chromatography	Mass spectrometryWestern blotting	2	37667547 36849061

Sequence, Structure & Domains8

Sequences

Length

228

Mass

25,416

Sequence

MPVKGGTKCIKYLLFGFNFIFWLAGIAVLAIGLWLRFDSQTKSIFEQETNNNNSSFYTGVYILIGAGALMMLVGFLGCCGAVQESQCMLGLFFGFLLVIFAIEIAAAIWGYSHKDEVIKEVQEFYKDTYNKLKTKDEPQRETLKAIHYALNCCGLAGGVEQFISDICPKKDVLETFTVKSCPDAIKEVFDNKFHIIGAVGIGIAVVMIFGMIFSMILCCAIRRNREMV

3D Structural Models

Turn

154..156; 169..172

Helix

5..37; 41..45; 55..82; 86..111; 114..133; 137..139; 140..150; 161..166; 173..175; 181..190; 193..222

3D Structure

X-ray crystallography (5)

Domain & Motif Annotations

Protein Families

Tetraspanin (TM4SF) family

Sequence Similarities

Belongs to the tetraspanin (TM4SF) family.

Clinical Relevance6

Disease Involvement

Cancer-related genes

Drugs (43)

Antibody

CAB002490

Interaction Protein (2)

ENSG00000110651ENSG00000134247

Interaction Count

Interaction Dataset (2)

biogrid_opencellintact_biogrid_opencell

Supporting Publications409

PMID	Title	Abstract
10545503	Molecular characterization of dendritic cell-derived exosomes. Selective accumulation of the heat shock protein hsc73.	Exosomes contain several cytosolic proteins (including annexin II, heat shock cognate protein hsc73, and heteromeric G protein Gi2alpha), as well as different integral or peripherally associated membrane proteins (major histocompatibility complex class II, Mac-1 integrin, CD9, milk fat globule-EGF-factor VIII [MFG-E8]). MFG-E8, the major exosomal component, binds integrins expressed by DCs and macrophages, suggesting that it may be involved in exosome targeting to these professional antigen-presenting cells.
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.
16027013	Human small intestinal epithelial cells constitutively express the key elements for antigen processing and the production of exosomes.	Interestingly, in the baso-latereral area of the IEC, only MHC II, MHC I, Lamp 1, CD68, CD63 and A33 were found and also here with vesicular staining pattern which matches the molecules previously found on exosomes derived professional APCs and human IEC lines. The IEC also contains MHC II rich multivesicular compartments and has been shown to produce exosomes.
16407131	Immature dendritic cell-derived exosomes can mediate HIV-1 trans infection.	Furthermore, some of the endocytosed virus particles were constitutively released into the extracellular milieu in association with HLA-DR1(+), CD1b(+), CD9(+), and CD63(+) vesicles (exosomes) and could initiate productive infections of CD4(+) target cells.
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.
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.
18802920	Secretion of active membrane type 1 matrix metalloproteinase (MMP-14) into extracellular space in microvesicular exosomes.	The exosomes were able to activate pro-MMP-2 and degrade type 1 collagen and gelatin, suggesting that the exosomal MT1-MMP was functionally active. The isolated exosomes were identified by their vesicular structure in electron microscopy and by exosomal marker proteins CD9 and tumor susceptibility gene (TSG101). The targeting of MT1-MMP in exosomes represents a novel mechanism for cancer cells to secrete membrane type metalloproteolytic activity into the extracellular space. Using cultured human fibrosarcoma (HT-1080) and melanoma (G361) cells we provide evidence that both the full-length 60 kDa and the proteolytically processed 43 kDa forms of MT1-MMP are secreted in exosomes. We hypothesized that some of the endosomal MT1-MMP could be directed to exosomes for extracellular release.
19810033	ExoCarta: A compendium of exosomal proteins and RNA.	Researchers rely on the identification of certain exosomal marker proteins including Alix, CD9 and CD63 to confirm the presence of exosomes in their preparations.

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