Affinage

CD9

CD9 antigen · UniProt P21926

Length
228 aa
Mass
25.4 kDa
Annotated
2026-06-09
100 papers in source corpus 37 papers cited in narrative 37 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 7/7 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

CD9 is a tetraspanin membrane protein whose reversed cone-like molecular shape generates and senses positive membrane curvature, driving its enrichment in high-curvature plasma-membrane structures and underpinning its role as an organizer of tetraspanin-enriched microdomains (PMID:32231207, PMID:36252000). It nucleates these microdomains through direct, domain-specific contacts: its large extracellular loop and fourth transmembrane domain engage the Ig-superfamily partners FPRP/CD9P-1 and EWI-2/EWI-F, with EWI-F binding occurring through CD9 transmembrane helices h3/h4 in a flexible tetrameric "concatenation" arrangement, and its C-terminal cytoplasmic tail tuning complex size and oligomerization (PMID:32958604, PMID:11278880, PMID:11087758, PMID:21771881). Microdomain assembly is regulated by site-specific S-palmitoylation: the acyltransferase DHHC2 palmitoylates CD9 to stabilize CD9-partner associations and protect CD9 from lysosomal degradation, while palmitoylation state and partner availability shift CD9 between homo- and heteroclusters (PMID:18508921, PMID:32181977, PMID:16537545). Through these scaffolding interactions CD9 governs membrane fusion and cell-cell organization—it is an indispensable oocyte-side component of sperm-egg fusion, prevents mononuclear phagocyte fusion, and restrains HIV-1 envelope-mediated fusion (PMID:32231207, PMID:12796480, PMID:17015697, PMID:23213457). CD9 also assembles and modulates cell-surface receptor and protease complexes: it scaffolds DPP4 and TMPRSS2 to promote early MERS-CoV entry, negatively regulates LPS-driven CD14/TLR4 receptor-complex formation, and binds metalloproteases CD10/ADAM17 to control ectodomain shedding of substrates including HB-EGF, AREG, and LR11 (PMID:28759649, PMID:19414803, PMID:23289620, PMID:24699135, PMID:30745837). By partnering with integrins, it supports integrin signaling at the immunological synapse and directs talin1-dependent focal-adhesion and cytoskeletal remodeling, influencing adhesion, migration, and tumor invasion (PMID:24723389, PMID:10669631, PMID:31685994). CD9 additionally promotes plasma-membrane localization of the glutamine transporter ASCT2 to fuel pancreatic tumor growth and acts on Wnt and PI3K-AKT-mTOR-p53 signaling (PMID:31685994, PMID:15334057, PMID:32346137).

Mechanistic history

Synthesis pass · year-by-year structured walk · 10 steps
  1. 2000 High

    Establishing the molecular identity of CD9's most stoichiometric partner answered whether tetraspanins form defined complexes; FPRP/CD9P-1 was shown to be essentially fully CD9/CD81-associated in discrete particles distinct from integrin complexes.

    Evidence Gel permeation chromatography, immunoprecipitation, immunodepletion and immunoaffinity/MS in 293 cells

    PMID:11087758 PMID:11278880

    Open questions at the time
    • Did not resolve the structural interface
    • Functional consequence of the CD9-FPRP complex not addressed
  2. 2002 High

    Identification of PSG17 as a CD9-specific natural ligand established that a tetraspanin can act as a bona fide receptor, answering whether CD9 engages defined extracellular ligands.

    Evidence cDNA library screening, binding assays, and CD9-knockout macrophage binding

    PMID:11805154

    Open questions at the time
    • Downstream signaling from PSG17-CD9 binding not defined
    • Physiological role of this binding in vivo not established
  3. 2003 High

    Genetic models clarified CD9's physiological role in cell fusion, showing it (with CD81) actively prevents inappropriate mononuclear phagocyte fusion rather than promoting it.

    Evidence In vitro fusion assays with antibody perturbation plus CD9/CD81 single- and double-null mice

    PMID:12796480

    Open questions at the time
    • Molecular mechanism restraining fusion not resolved
    • Partner dependence of fusion suppression unclear
  4. 2008 High

    Identifying DHHC2 as the palmitoyl acyltransferase for CD9 answered how CD9 complexes and protein stability are post-translationally controlled.

    Evidence DHHC knockdown, active-site mutagenesis, [3H]palmitate labeling, and co-IP

    PMID:18508921

    Open questions at the time
    • Depalmitoylating enzyme not identified
    • Dynamics of palmitoylation turnover in vivo not measured
  5. 2011 Medium

    Domain dissection of the C-terminal tail and homo/heterocluster studies answered how CD9 molecular organization is encoded, linking the tail and palmitoylation to complex size and cluster state.

    Evidence C-tail mutagenesis with SILAC proteomics and functional assays; homo-clustering probe with palmitoylation mutants

    PMID:16537545 PMID:21771881

    Open questions at the time
    • Cluster transitions inferred from antibody probe, not direct imaging at the time
    • Single-lab findings
  6. 2013 Medium

    Mapping the CD9-CD10/ADAM17 interactions established CD9 as a regulator of cell-surface metalloprotease activity and of protease cargo loading into extracellular vesicles.

    Evidence CD9/CD82 chimeras, mutagenesis, knockdown/overexpression and exosome quantification

    PMID:23289620 PMID:24699135 PMID:30745837

    Open questions at the time
    • Whether CD9 directly inhibits catalysis or sequesters substrate unresolved
    • Sheddase regulation tested largely in single-lab systems
  7. 2017 High

    The DPP4:CD9:TMPRSS2 scaffolding model answered how CD9 dictates viral entry kinetics, showing CD9 assembles receptor-protease complexes that route MERS-CoV to rapid surface entry.

    Evidence CD9 knockout cells, co-IP, pseudovirus entry, and in vivo hDPP4 mouse model with CD9 silencing

    PMID:28759649

    Open questions at the time
    • Structural basis of the trimolecular scaffold not solved
    • Generality to other receptor-protease pairs untested
  8. 2019 High

    Linking CD9 to ASCT2 surface localization answered how a scaffolding tetraspanin can drive tumor metabolism, connecting CD9 to glutamine-fueled pancreatic cancer growth.

    Evidence Knockdown, heterozygous CD9 deletion in a PDAC mouse model, surface localization and glutamine uptake assays

    PMID:31685994

    Open questions at the time
    • Direct CD9-ASCT2 binding interface not mapped
    • Mechanism of ASCT2 surface retention by CD9 unresolved
  9. 2020 High

    Atomic structures of CD9 and its EWI-2/EWI-F complexes answered the long-standing question of how tetraspanins shape membranes and assemble microdomains, revealing curvature generation and a flexible concatenation model.

    Evidence X-ray crystallography, cryo-EM of CD9-EWI complexes, fertilization assay, and native MS of palmitoylation-dependent EWI-F binding

    PMID:32181977 PMID:32231207 PMID:32958604

    Open questions at the time
    • Higher-order microdomain architecture in native membranes not directly visualized
    • Lipid composition dependence of curvature in cells not defined
  10. 2022 High

    Biophysical reconstitution established CD9 as a curvature sensor preferring positive curvature, providing a physical basis for its enrichment at microvilli and other curved structures.

    Evidence Biomimetic membrane tube assays from giant plasma membrane vesicles with thermodynamic modeling

    PMID:36252000

    Open questions at the time
    • In-cell validation of curvature sorting limited
    • Interplay between curvature sensing and partner binding not quantified

Open questions

Synthesis pass · forward-looking unresolved questions
  • How CD9's biophysical curvature/scaffolding properties are mechanistically coupled to its many context-specific signaling outputs (Wnt, PI3K-AKT-mTOR-p53, integrin/FAK, cytoskeletal WAVE2 control) remains unresolved.
  • No unifying mechanism connecting microdomain assembly to downstream signaling cascades
  • Many signaling roles rest on single-lab perturbation studies

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0060090 molecular adaptor activity 5 GO:0098772 molecular function regulator activity 3 GO:0008289 lipid binding 2 GO:0001618 virus receptor activity 1
Localization
GO:0005886 plasma membrane 5 GO:0031410 cytoplasmic vesicle 3 GO:0005768 endosome 2
Pathway
R-HSA-1474244 Extracellular matrix organization 3 R-HSA-1643685 Disease 3 R-HSA-168256 Immune System 3 R-HSA-392499 Metabolism of proteins 3 R-HSA-1474165 Reproduction 2
Partners
ADAM17DPP4IGSF8ITGB1MMEPTGFRNSLC1A5TMPRSS2
Complex memberships
DPP4:CD9:TMPRSS2 receptor-protease complextetraspanin-enriched microdomain

Evidence

Reading pass · 37 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2020 Crystal structure of CD9 and cryo-EM structure of CD9 in complex with EWI-2 revealed that CD9's reversed cone-like molecular shape generates membrane curvature in crystalline lipid layers, explaining its localization in high-curvature membrane regions. The CD9–EWI-2 interaction is primarily mediated through small residues in the transmembrane region and protein/lipid interactions, while the large extracellular loop (LEL) region is critical for sperm-egg fusion. X-ray crystallography (CD9 alone) and cryo-electron microscopy (CD9 with EWI-2); fertilization functional assay Nature communications High 32231207
2020 Cryo-EM structure of CD9 in complex with its partner EWI-F revealed a tetrameric arrangement: two central EWI-F molecules dimerized through ectodomains and two CD9 molecules each bound to one EWI-F transmembrane helix via CD9 helices h3 and h4. This flexible arrangement suggests a 'concatenation model' for tetraspanin-enriched microdomain assembly. Cryo-EM structure; crystal structures of CD9 LEL bound to nanobodies 4C8 and 4E8 Life science alliance High 32958604
2022 CD9 (and tetraspanin4) function as curvature sensors with preference for positive membrane curvature, demonstrated using biomimetic membrane tubes pulled from giant plasma membrane vesicles. This sensing property explains CD9 enrichment in curved structures such as oocyte microvilli. Biomimetic membrane tube assay from giant plasma membrane vesicles with controllable tension and curvature; thermodynamic modeling Proceedings of the National Academy of Sciences of the United States of America High 36252000
2001 CD9's major binding partner identified as CD9P-1 (encoded by KIAA1436, human ortholog of rat FPRP), a 135-kDa cell-surface Ig superfamily protein. Cross-linking experiments showed direct CD9–CD9P-1 association. Chimeric CD9/CD82 molecules revealed that the second half of CD9 (large extracellular loop and fourth transmembrane domain) mediates this interaction. CD9P-1 also associates separately with CD81. Immunoaffinity purification, mass spectrometry, cross-linking experiments, chimeric protein analysis The Journal of biological chemistry High 11278880
2000 FPRP (prostaglandin F2α receptor regulatory protein, 133 kDa) is the most stoichiometric and specific CD9- and CD81-associated protein: essentially 100% of cell-surface FPRP on 293 cells is CD81- and CD9-associated. CD81·CD9·FPRP complexes are discrete in size (<4×10^6 Da) and distinct from integrin-containing CD81 complexes, as shown by immunoprecipitation and immunodepletion. Gel permeation chromatography, immunoprecipitation, immunodepletion, methyl-β-cyclodextrin treatment The Journal of biological chemistry High 11087758
2008 DHHC2 is the palmitoyl acyltransferase responsible for palmitoylation of CD9 and CD151. DHHC2 physically associates with CD9 and CD151 but not other cell-surface proteins; inactive DHHC2 (DH→AA or C→S mutations) fails to palmitoylate them. DHHC2-dependent palmitoylation promotes CD9–CD151 physical associations, protects CD9 and CD151 from lysosomal degradation, and shifts cells toward increased cell-cell contacts. DHHC protein knockdown, active-site mutagenesis, [³H]palmitate labeling, co-immunoprecipitation, functional cell morphology assays Molecular biology of the cell High 18508921
2020 Site-specific palmitoylation of CD9 at its three most frequently lipidated cysteine sites is required for EWI-F binding; cysteine-to-alanine mutations markedly reduced EWI-F binding, whereas tryptophan substitutions at those sites rescued binding. Native mass spectrometry revealed nonstochastic distributions of bound acyl chains on wild-type CD9. Native mass spectrometry, cysteine-to-alanine and tryptophan mutagenesis, EWI-F binding assay, super-resolution microscopy with CD9-specific nanobody The FEBS journal High 32181977
2006 Cell-surface CD9 homo-clustering is promoted by α3β1 and α6β4 integrins and by palmitoylation of CD9 and β4; CD9 is shifted toward heteroclusters by EWI-2, EWI-F, other tetraspanins, or ablation of CD9 palmitoylation. Unpalmitoylated CD9 shows enhanced EWI-2 association, indicating that depalmitoylation and EWI-2 binding collaborate to shift CD9 from homo- to heteroclusters. Low-affinity anti-CD9 antibody C9BB detecting homo-clustered CD9; expression of EWI-2/EWI-F, integrins, palmitoylation mutants; co-immunoprecipitation The Journal of biological chemistry Medium 16537545
2013 CD9 directly associates with the metalloprotease CD10; the interaction requires the portion of CD9's large extracellular loop from the CCG motif to TM4 and the C-terminal cytoplasmic tail (identified by CD9/CD82 chimeras and site-directed mutagenesis). CD9 expression enhances CD10 release in exosomes ~5-fold, while the CD9 C-terminal tail domain is required for this effect on exosomal release. CD9 knockdown reduces endogenous CD10 release in microvesicles ~2-fold. CD9/CD82 chimeras, site-directed mutagenesis, stable CD9 expression, shRNA knockdown, co-immunoprecipitation, exosome isolation and quantification The FEBS journal High 23289620
2011 The C-terminal tail of CD9 (three residues Glu-Met-Val) is required for inhibition of cell adhesion/spreading on fibronectin, promotion of homotypic cell-cell aggregation, and microvilli formation. Mutant CD9 (C-tail replaced with CD82 residues) shows reduced recovery with its major transmembrane interacting partners in Brij 96 and forms larger, more oligomerized complexes, indicating the tail regulates CD9 molecular organization. C-terminal tail mutagenesis (EMV→PKY substitution), SILAC quantitative proteomics, co-immunoprecipitation, functional adhesion/aggregation assays in multiple cell lines Journal of cell science High 21771881
2017 CD9 scaffolds the MERS-CoV receptor DPP4 and the protease TMPRSS2 into cell-surface complexes (DPP4:CD9:TTSP), enabling rapid early viral entry via TMPRSS2 cleavage. Without CD9, MERS-CoV traffics to endosomes for later, less efficient cathepsin-mediated activation. In vivo, CD9 silencing in mice sensitized to MERS-CoV by hDPP4 expression significantly reduced susceptibility to infection. CD9 knockout cell lines, Co-IP of DPP4/TMPRSS2/CD9, MERS-CoV pseudovirus entry assays, in vivo rAd5-hDPP4 mouse model with CD9 siRNA silencing PLoS pathogens High 28759649
2002 Murine CD9 is the receptor for pregnancy-specific glycoprotein 17 (PSG17), the first identified natural ligand for a tetraspanin. PSG17 binding is specific to CD9 and not to CD53, CD63, CD81, CD82, or CD151. Anti-CD9 antibody inhibits PSG17 binding, and macrophages from CD9-deficient mice show significantly reduced PSG17 binding. cDNA expression library screening, ELISA, flow cytometry, alkaline phosphatase binding assay, in situ rosetting, CD9-knockout macrophage binding assay The Journal of experimental medicine High 11805154
2003 CD9 and CD81 function to prevent fusion of mononuclear phagocytes (monocytes, alveolar macrophages). CD9 and CD81 expression and their integrin complex formation are up-regulated during normal monocyte culture and down-regulated under fusogenic conditions. Anti-CD9/CD81 antibodies promoted fusion; CD9/CD81 double-null mice spontaneously developed multinucleated giant cells in lung and showed enhanced osteoclastogenesis. In vitro monocyte/macrophage fusion assays, anti-tetraspanin antibody perturbation, CD9-null and CD81-null mouse models, in vivo lung histology and bone analysis The Journal of cell biology High 12796480
2006 CD9 (and CD81) negatively regulate HIV-1 envelope-mediated membrane fusion. Knockdown of CD9 or CD81 increased syncytia formation and viral entry; overexpression rendered cells less susceptible. Anti-CD81 antibodies triggered CD81 clustering in patches that recruited CD4 and CXCR4. siRNA knockdown, overexpression, anti-tetraspanin antibody treatment, HIV-1 Env-mediated syncytia and viral entry assays in human T lymphoblasts Journal of immunology Medium 17015697
2009 CD9 negatively regulates LPS-induced macrophage activation by preventing the formation of the LPS receptor complex (CD14/TLR4) at lipid rafts. CD9 partly co-localizes with CD14 at low-density membrane fractions. CD9 knockout macrophages show increased CD14 and TLR4 lipid-raft localization, increased CD14:TLR4 complex formation, decreased IκBα expression, and produce more TNF-α, MMP-2 and MMP-9 after LPS stimulation. CD9-KO mice showed enhanced lung macrophage infiltration and TNF-α production after intranasal LPS. Anti-CD9 mAb, siRNA, CD9 knockout mice, sucrose gradient fractionation, co-immunoprecipitation, in vitro and in vivo LPS challenge assays Journal of immunology High 19414803
2019 CD9 promotes plasma membrane localization of the glutamine transporter ASCT2, enhancing glutamine uptake in pancreatic cancer cells. CD9 knockdown decreases PDAC organoid growth; heterozygous CD9 deletion in a PDAC mouse model prolonged survival. CD9 knockdown (siRNA/shRNA), CD9 heterozygous deletion in Pdx1-Cre;KRas;p53 mice, ASCT2 surface localization by cell fractionation/imaging, glutamine uptake assay, organoid formation and limiting dilution tumor initiation assays Nature cell biology High 31685994
2004 CD9 (MRP-1/CD9) gene transduction downregulates Wnt pathway genes (Wnt1, Wnt2b1, Wnt5a) and their target genes (WISP-1, WISP-3, c-Myc, VEGF-A, MMP-26), placing CD9 upstream of Wnt signaling. A neutralizing anti-CD9 antibody inhibited this downregulation in CD9-transfected cells. CD9 gene transduction into HT1080 and A549 cells, microarray and real-time PCR, Western blotting, neutralizing anti-CD9 antibody treatment Oncogene Medium 15334057
2006 CD9 gene transduction downregulates WAVE2 expression and alters subcellular localization of Arp2 and Arp3, reducing lamellipodia formation and cell motility. This effect is independent of the Wnt signaling pathway, as Wnt siRNA did not affect WAVE2 and WAVE2 siRNA did not affect Wnt expression. CD9 gene transduction in HT1080 cells, WAVE2-specific siRNA, neutralizing anti-CD9 antibody, morphological analysis, time-lapse migration assay Oncogene Medium 16682943
2011 CD9 specifically controls localization of talin1 to focal adhesions: CD9 deficiency leads to impaired talin1 focal adhesion localization and correlates with increased motility of breast cancer cells. CD9-deficient cells, talin1 focal adhesion localization by imaging, cell motility assays Biochemical Society transactions Low 21428940
2014 CD9 and CD151 accumulate at the T-cell side of the immunological synapse and support integrin-mediated signaling: silencing CD9 or CD151 reduces α4β1 integrin relocalization to the IS, decreases high-affinity β1 integrin accumulation, diminishes FAK and ERK1/2 phosphorylation, and impairs IL-2 secretion and CD69 upregulation without affecting CD3/actin accumulation or MTOC translocation. CD9/CD151 siRNA silencing, T cell–APC conjugate assays, confocal imaging of IS components, phospho-FAK and phospho-ERK Western blotting, IL-2 ELISA European journal of immunology Medium 24723389
2014 CD9 co-immunoprecipitates with ADAM17 at the cell surface and negatively modulates ADAM17-mediated shedding of LR11 in leukocytes: CD9 overexpression reduces soluble LR11 release, while CD9 knockdown or antibody neutralization increases sLR11 shedding via metalloproteinase-dependent mechanism. Confocal co-localization, ectopic CD9 expression, CD9 shRNA knockdown, anti-CD9 neutralizing antibody, metalloproteinase inhibitor GM6001, ELISA for soluble LR11 Experimental & molecular medicine Medium 24699135
2019 CD9 physically associates with ADAM17 at the keratinocyte surface (co-IP confirmed) and negatively regulates ADAM17 sheddase activity. CD9 downregulation activates ADAM17, leading to shedding of HB-EGF and AREG and subsequent EGFR/ERK pathway activation that drives keratinocyte migration and wound healing. Confocal co-localization, co-immunoprecipitation, CD9 siRNA knockdown and overexpression, TAPI-2 (ADAM17 inhibitor), neutralizing anti-HB-EGF antibody, EGFR/ERK phosphorylation assays, wound-healing migration assays in HaCaT cells and primary mouse keratinocytes International journal of biological sciences Medium 30745837
2020 CD9 regulates cellular senescence through the PI3K–AKT–mTOR–p53 signaling pathway: CD9 knockdown in senescent endothelial cells rescues senescence phenotypes, and CD9 upregulation in young cells accelerates senescence. Anti-CD9 antibody treatment and CD9 ablation (ApoE-/- mice) reduced atherosclerotic lesion formation in vivo. CD9 knockdown and overexpression in HUVECs, senescence assays, PI3K/AKT/mTOR/p53 pathway Western blotting, anti-CD9 antibody treatment in ApoE-/- and Ldlr-/- mice, CD9-KO crossed to ApoE-/- mice Cell death and differentiation Medium 32346137
2014 CD9 co-precipitates with CD26 in mesothelioma cells, and these proteins inversely co-modulate each other's expression. CD9 depletion leads to elevated FAK and Cas-L tyrosine phosphorylation (downstream of β1 integrin), and increased invasiveness, suggesting CD9 negatively regulates tumor invasion by reducing the CD26–α5β1 integrin complex. siRNA knockdown of CD9 and CD26, co-immunoprecipitation, Western blotting for FAK/Cas-L phosphorylation, cell invasion assay PloS one Medium 24466195
2001 CD9 antibody ligation increases human CFU-MK progenitor numbers and reduces megakaryocytic differentiation (decreased CD41+ cell production and MK differentiation antigen expression) in liquid culture, suggesting CD9 participates in megakaryocytic differentiation by involvement in membrane remodeling. Cell sorting, liquid culture with anti-CD9 antibody ligation, CFU-MK colony assays, flow cytometry for differentiation markers Blood Medium 11264162
2010 CD9P-1 overexpression increases cell motility on collagen I via α2β1 integrin but decreases motility on fibronectin; co-expression of CD9 or CD81 reverses these CD9P-1-mediated motility effects with concomitant CD9P-1 association, showing that the ratio of CD9P-1 to its tetraspanin partners regulates cell motility. CD9P-1 overexpression, CD9/CD81 co-expression, CD9P-1 mutant analysis (transmembrane and cytoplasmic domains required), co-immunoprecipitation, time-lapse videomicroscopy, Boyden chamber assay PloS one Medium 20574531
2000 CD9 co-localizes with β1 and β3 integrins on endothelial cell membranes, and anti-CD9 antibody induces tyrosine phosphorylation comparable to β1/β3 integrin ligation. Blocking CD9 with mAb ALMA.1 inhibits EC migration toward fibronectin and vitronectin and impairs wound repair, and ALMA.1 and anti-β1 have additive inhibitory effects, suggesting CD9 cooperates with integrins in EC migration. Double-labeling immunofluorescence for CD9/integrins, anti-CD9 mAb perturbation, in vitro wound-healing assay, Boyden chamber migration assay, tyrosine phosphorylation Western blotting Arteriosclerosis, thrombosis, and vascular biology Medium 10669631
1999 Stromal cell CD9 associates with the β1 integrin subunit and a novel 100 kDa protein (co-immunoprecipitation); antibody cross-linking of CD9 increased the amount of the 100 kDa protein co-precipitated. Ligation of stromal-cell CD9 (but not hematopoietic-cell CD9) modifies hematopoietic progenitor differentiation, shifting pluripotent EML-C1 cells toward undifferentiated, clonogenic states. Co-culture with anti-CD9 antibody, separate cell pre-treatment to identify the responding cell type, co-immunoprecipitation, colony-forming unit assays Blood Medium 10194438
2012 CD9 and CD81 are present as separate, non-complexed extracellular structures in bilayers on the oocyte surface; microinjection of CD9 RNA rescued fusion defects in both CD9-deficient and CD81-deficient oocytes, whereas CD81 failed to rescue either, indicating CD9 and CD81 function independently as extracellular components in sperm-oocyte fusion. Immunocytochemistry, immunobiochemistry, electron microscopy, RNA microinjection rescue experiments in CD9-KO and CD81-KO oocytes Biology open Medium 23213457
2021 CD9 localizes primarily to the plasma membrane, where it is secreted more abundantly in ectosomes than in exosomes. CD9 and a PM-stabilized CD63 mutant are more abundantly released in EVs than wild-type CD63. Comparative proteomics identified BSG and SLC3A2 as likely ectosome-specific proteins, distinct from the exosomal marker LAMP1. Live intracellular tracking of CD9 and CD63, comparative proteomics, differential response to endosomal pH neutralization, subcellular fractionation Nature communications Medium 34282141
2023 Concomitant knockout of CD9 and CD81 in MCF7 cells specifically reduces EV levels of CD9P-1/PTGFRN and EWI-2/IGSF8 (the sole significantly decreased EV proteins), partially because of decreased cell expression of EWI-2. Single KO of CD9, CD81, or CD63 had little effect on overall EV protein composition. CD9, CD81, CD63 single and double knockout by CRISPR, quantitative mass spectrometry proteomics of EVs Journal of extracellular vesicles Medium 37525398
2015 CD9 knockdown in MDA-MB-231 breast cancer cells inhibits MSC invasion by 95% and anti-CD9 antibody blockade by 70%; CD9-deficient cells lose magnupodium/lamellipodium structures and gain membrane ruffles, which impairs adhesion and invasiveness. CD9 knockdown also suppresses metastatic capacity in mouse xenografts. CD9 shRNA knockdown, anti-CD9 antibody blockade, TIRF/confocal/scanning EM microscopy, mouse xenograft metastasis model Oncotarget Medium 25762645
2002 Down-regulation of CD9 mRNA expression in Schwann cells follows axonal degeneration after sciatic nerve injury and is restored upon axonal regeneration; in culture, CD9 expression requires contact with neurons. This parallels myelin gene regulation, suggesting axons regulate CD9 expression in Schwann cells. Adult rat sciatic nerve injury model, in situ hybridization for CD9 mRNA, Schwann cell–neuron co-culture experiments Molecular and cellular neurosciences Medium 8581316
2015 In Drosophila, tetraspanin tsp2A (close homolog of human CD9) genetically interacts with Pvr (PDGFR homolog), and tsp2A knockdown partially rescues Pvr-induced glial over-migration. In human glioma cells, CD9 is in close association with PDGFRα and PDGFRβ (proximity ligation assay), and CD9 knockdown blocks PDGF-BB-stimulated cell migration. Drosophila genetic screen with dsRNA, in situ proximity ligation assay for CD9-PDGFR association, CD9 siRNA knockdown in human glioma cells with PDGF-stimulated migration assay Journal of neuro-oncology Medium 26224160
1997 CD9 expression is upregulated ~7-fold during TPA-induced megakaryocytic differentiation of K562 cells via PKC activation (blocked by GF109203X), and upregulated CD9 associates with β1 integrin. A TPA-responsive element was localized to a 52-bp fragment of the CD9 promoter. TPA treatment, PKC inhibitor GF109203X, quantitative RT-PCR, flow cytometry, co-immunoprecipitation, CD9 promoter-CAT reporter constructs Leukemia Medium 9264383
2021 CD9 inhibition (by cytopermeable blocking peptides or gene deletion) reduces the number of early endosomes and affects mitochondrial quality control, specifically impairing mitophagy; CD9 KO cells compensate by increasing total mitochondrial mass and reducing mitophagy. CD9 peptide treatment delayed primary tumor growth and reduced metastasis in vivo. CD9-blocking peptides vs. CD9 gene deletion comparison, endosome and lysosome quantification, mitochondrial mass and mitophagy assays, in vivo melanoma model Journal of extracellular vesicles Low 34012515
2022 JAM-A forms a complex with α3β1 integrin and tetraspanins CD151 and CD9 through its extracellular domain (by mapping experiments), and this complex is required for collective cell migration of polarized epithelial cells on laminin and collagen-I substrates. JAM-A/CD9/CD151/α3β1 integrin depletion by siRNA in MDCK cells, co-immunoprecipitation and domain mapping, collective migration assay (scratch wound, live imaging) Cellular and molecular life sciences Medium 35067832

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2021 Specificities of exosome versus small ectosome secretion revealed by live intracellular tracking of CD63 and CD9. Nature communications 693 34282141
2001 The major CD9 and CD81 molecular partner. Identification and characterization of the complexes. The Journal of biological chemistry 193 11278880
2020 Structural insights into tetraspanin CD9 function. Nature communications 165 32231207
2003 Tetraspanins CD9 and CD81 function to prevent the fusion of mononuclear phagocytes. The Journal of cell biology 163 12796480
1998 Correlation of reduction in MRP-1/CD9 and KAI1/CD82 expression with recurrences in breast cancer patients. The American journal of pathology 162 9736046
1995 Motility related protein 1 (MRP-1/CD9) expression: inverse correlation with metastases in breast cancer. Cancer research 139 7664290
2018 Tetraspanin CD9: A Key Regulator of Cell Adhesion in the Immune System. Frontiers in immunology 131 29760699
2006 Tetraspanins CD9 and CD81 modulate HIV-1-induced membrane fusion. Journal of immunology (Baltimore, Md. : 1950) 131 17015697
2017 The tetraspanin CD9 facilitates MERS-coronavirus entry by scaffolding host cell receptors and proteases. PLoS pathogens 126 28759649
2018 CD9 Tetraspanin: A New Pathway for the Regulation of Inflammation? Frontiers in immunology 120 30356731
2000 FPRP, a major, highly stoichiometric, highly specific CD81- and CD9-associated protein. The Journal of biological chemistry 118 11087758
2019 CD9 identifies pancreatic cancer stem cells and modulates glutamine metabolism to fuel tumour growth. Nature cell biology 113 31685994
2023 Differential proteomics argues against a general role for CD9, CD81 or CD63 in the sorting of proteins into extracellular vesicles. Journal of extracellular vesicles 105 37525398
2000 The microneme protein MIC3 of Toxoplasma gondii is a secretory adhesin that binds to both the surface of the host cells and the surface of the parasite. Cellular microbiology 100 11207591
2017 The Impact of the CD9 Tetraspanin on Lentivirus Infectivity and Exosome Secretion. Molecular therapy : the journal of the American Society of Gene Therapy 94 29221804
2013 Tetraspanin protein CD9 interacts with metalloprotease CD10 and enhances its release via exosomes. The FEBS journal 92 23289620
1998 Motility related protein 1 (MRP1/CD9) expression in colon cancer. Clinical cancer research : an official journal of the American Association for Cancer Research 91 9626469
2017 Exosomal Markers (CD63 and CD9) Expression Pattern Using Immunohistochemistry in Resected Malignant and Nonmalignant Pancreatic Specimens. Pancreas 84 28609367
2009 Tetraspanin CD9 negatively regulates lipopolysaccharide-induced macrophage activation and lung inflammation. Journal of immunology (Baltimore, Md. : 1950) 83 19414803
2003 The MIC3 gene of Toxoplasma gondii is a novel potent vaccine candidate against toxoplasmosis. Infection and immunity 80 14573640
2008 DHHC2 affects palmitoylation, stability, and functions of tetraspanins CD9 and CD151. Molecular biology of the cell 79 18508921
1995 An anti-CD9 monoclonal antibody promotes adhesion and induces proliferation of Schwann cells in vitro. The Journal of neuroscience : the official journal of the Society for Neuroscience 78 7823165
2002 Murine CD9 is the receptor for pregnancy-specific glycoprotein 17. The Journal of experimental medicine 76 11805154
2011 Tetraspanin CD9 in cell migration. Biochemical Society transactions 71 21428940
2007 Adenoviral transduction of MRP-1/CD9 and KAI1/CD82 inhibits lymph node metastasis in orthotopic lung cancer model. Cancer research 71 17308116
2009 Expression of multidrug resistance markers ABCB1 (MDR-1/P-gp) and ABCC1 (MRP-1) in renal cell carcinoma. BMC urology 69 19552816
2016 Transmembrane protein CD9 is glioblastoma biomarker, relevant for maintenance of glioblastoma stem cells. Oncotarget 67 26573230
2015 A regulatory CD9(+) B-cell subset inhibits HDM-induced allergic airway inflammation. Allergy 66 26194936
2010 Cell surface tetraspanin CD9 mediates chemoresistance in small cell lung cancer. Cancer research 65 20940407
2020 CD9 induces cellular senescence and aggravates atherosclerotic plaque formation. Cell death and differentiation 64 32346137
2002 The Toxoplasma gondii protein MIC3 requires pro-peptide cleavage and dimerization to function as adhesin. The EMBO journal 62 12032066
2001 CD9 and megakaryocyte differentiation. Blood 58 11264162
2012 CD81 and CD9 work independently as extracellular components upon fusion of sperm and oocyte. Biology open 57 23213457
2007 Down-regulation of CD9 expression during prostate carcinoma progression is associated with CD9 mRNA modifications. Clinical cancer research : an official journal of the American Association for Cancer Research 57 17406028
2004 MRP-1/CD9 gene transduction downregulates Wnt signal pathways. Oncogene 57 15334057
2000 CD9 participates in endothelial cell migration during in vitro wound repair. Arteriosclerosis, thrombosis, and vascular biology 57 10669631
2022 Transmembrane proteins tetraspanin 4 and CD9 sense membrane curvature. Proceedings of the National Academy of Sciences of the United States of America 56 36252000
2018 CD9+ Regulatory B Cells Induce T Cell Apoptosis via IL-10 and Are Reduced in Severe Asthmatic Patients. Frontiers in immunology 55 30622536
2015 Tetraspanin CD9 determines invasiveness and tumorigenicity of human breast cancer cells. Oncotarget 55 25762645
2014 Tetraspanins CD9 and CD151 at the immune synapse support T-cell integrin signaling. European journal of immunology 54 24723389
2023 Lack of involvement of CD63 and CD9 tetraspanins in the extracellular vesicle content delivery process. Communications biology 53 37198427
2004 CD9 expression in gastric cancer and its significance. The Journal of surgical research 53 15047125
2006 Contrasting effects of EWI proteins, integrins, and protein palmitoylation on cell surface CD9 organization. The Journal of biological chemistry 51 16537545
2021 CD9, a tetraspanin target for cancer therapy? Experimental biology and medicine (Maywood, N.J.) 49 33601913
1999 Stromal cell CD9 regulates differentiation of hematopoietic stem/progenitor cells. Blood 48 10194438
2000 Suppression of pulmonary metastasis using adenovirally motility related protein-1 (MRP-1/CD9) gene delivery. Oncogene 45 11077438
2021 CD9 inhibition reveals a functional connection of extracellular vesicle secretion with mitophagy in melanoma cells. Journal of extracellular vesicles 43 34012515
2013 Evaluation of protective effect of multiantigenic DNA vaccine encoding MIC3 and ROP18 antigen segments of Toxoplasma gondii in mice. Parasitology research 43 23591483
2008 Molecular signals in the trafficking of Toxoplasma gondii protein MIC3 to the micronemes. Eukaryotic cell 41 18390648
2020 KLF4-mediated upregulation of CD9 and CD81 suppresses hepatocellular carcinoma development via JNK signaling. Cell death & disease 40 32350244
2005 Multidrug resistance-associated protein MRP-1 regulates dauer diapause by its export activity in Caenorhabditis elegans. Development (Cambridge, England) 39 15983401
2012 Detection and characterisation of multi-drug resistance protein 1 (MRP-1) in human mitochondria. British journal of cancer 38 22353810
2015 Novel CD9-targeted therapies in gastric cancer. World journal of gastroenterology 37 25805926
1996 Expression and distribution of CD9 in myelin of the central and peripheral nervous systems. The American journal of pathology 36 8701996
2019 Characterization of Moringa oleifera roots polysaccharide MRP-1 with anti-inflammatory effect. International journal of biological macromolecules 34 30936009
2009 Protective immune response in BALB/c mice induced by a suicidal DNA vaccine of the MIC3 gene of Toxoplasma gondii. Veterinary parasitology 34 19592172
2015 Sdf-1 (CXCL12) induces CD9 expression in stem cells engaged in muscle regeneration. Stem cell research & therapy 32 25890097
2020 Implications for tetraspanin-enriched microdomain assembly based on structures of CD9 with EWI-F. Life science alliance 31 32958604
2014 CD9 negatively regulates CD26 expression and inhibits CD26-mediated enhancement of invasive potential of malignant mesothelioma cells. PloS one 30 24466195
2008 Evaluation of a recombinant MIC3 based latex agglutination test for the rapid serodiagnosis of Toxoplasma gondii infection in swines. Veterinary parasitology 30 18783889
2016 MYCN and HDAC5 transcriptionally repress CD9 to trigger invasion and metastasis in neuroblastoma. Oncotarget 29 27572323
2011 Evaluation of immune responses induced by SAG1 and MIC3 vaccine cocktails against Toxoplasma gondii. Veterinary parasitology 29 22336771
2012 Induction of immune responses in sheep by vaccination with liposome-entrapped DNA complexes encoding Toxoplasma gondii MIC3 gene. Polish journal of veterinary sciences 28 22708351
1997 MRP-1/CD9 and KAI1/CD82 expression in normal and various cancer tissues. International journal of oncology 28 21528303
2022 JAM-A interacts with α3β1 integrin and tetraspanins CD151 and CD9 to regulate collective cell migration of polarized epithelial cells. Cellular and molecular life sciences : CMLS 27 35067832
2010 The tetraspanins CD9 and CD81 regulate CD9P1-induced effects on cell migration. PloS one 27 20574531
2011 The C-terminal tail of tetraspanin protein CD9 contributes to its function and molecular organization. Journal of cell science 26 21771881
2010 Expression and function of CD9 in melanoma cells. Molecular carcinogenesis 26 19777564
2024 Distinctive CD39+CD9+ lung interstitial macrophages suppress IL-23/Th17-mediated neutrophilic asthma by inhibiting NETosis. Nature communications 24 39366998
2013 Roles for HB-EGF and CD9 in multiple sclerosis. Glia 24 24038577
2011 Immunogenicity and protective efficacy of two recombinant pseudorabies viruses expressing Toxoplasma gondii SAG1 and MIC3 proteins. Veterinary parasitology 24 21632181
2014 Tetraspanin CD9 modulates ADAM17-mediated shedding of LR11 in leukocytes. Experimental & molecular medicine 23 24699135
2021 Inhibition of cancer-cell migration by tetraspanin CD9-binding peptide. Chemical communications (Cambridge, England) 21 33870995
2019 CD9 regulates keratinocyte migration by negatively modulating the sheddase activity of ADAM17. International journal of biological sciences 21 30745837
2009 Further analysis of protection induced by the MIC3 DNA vaccine against T. gondii: CD4 and CD8 T cells are the major effectors of the MIC3 DNA vaccine-induced protection, both Lectin-like and EGF-like domains of MIC3 conferred protection. Vaccine 21 19428907
2003 CD9 expression on lymphatic vessels in head and neck mucosa. Modern pathology : an official journal of the United States and Canadian Academy of Pathology, Inc 21 14559986
1993 Organization of the human CD9 gene. Genomics 21 8486348
2021 Protective efficacy by a novel multi-epitope vaccine, including MIC3, ROP8, and SAG1, against acute Toxoplasma gondii infection in BALB/c mice. Microbial pathogenesis 20 33548480
2015 MDR-1 and MRP-1 activity in peripheral blood leukocytes of rheumatoid arthritis patients. Diagnostic pathology 20 26715450
2002 CD9 expression in solid non-neuroepithelial tumors and infiltrative astrocytic tumors. The journal of histochemistry and cytochemistry : official journal of the Histochemistry Society 20 12185197
2015 MIC3, a novel cross-protective antigen expressed in Toxoplasma gondii and Neospora caninum. Parasitology research 19 26141436
2010 Functional and biochemical studies of CD9 in fibrosarcoma cell line. Molecular and cellular biochemistry 19 21161334
2002 Down-regulation of macrophage CD9 expression by interferon-gamma. Biochemical and biophysical research communications 19 11798156
1997 Upregulation of CD9 expression during TPA treatment of K562 cells. Leukemia 19 9264383
1995 Schwann cell CD9 expression is regulated by axons. Molecular and cellular neurosciences 19 8581316
2022 A Cd9+Cd271+ stem/progenitor population and the SHP2 pathway contribute to neonatal-to-adult switching that regulates tendon maturation. Cell reports 18 35476985
2020 Site-specific functionality and tryptophan mimicry of lipidation in tetraspanin CD9. The FEBS journal 18 32181977
2018 CD9 expression indicates a poor outcome in acute lymphoblastic leukemia. Cancer biomarkers : section A of Disease markers 18 29286918
2016 Identification of a TNF-α inducer MIC3 originating from the microneme of non-cystogenic, virulent Toxoplasma gondii. Scientific reports 18 28000706
2023 A peptide binding to the tetraspanin CD9 reduces cancer metastasis. Biomaterials advances 17 36640525
2020 Electric field down-regulates CD9 to promote keratinocytes migration through AMPK pathway. International journal of medical sciences 17 32308539
2020 Tetraspanin CD9 affects HPV16 infection by modulating ADAM17 activity and the ERK signalling pathway. Medical microbiology and immunology 17 32385608
2016 Toxoplasma gondii: Protective immunity induced by a DNA vaccine expressing GRA1 and MIC3 against toxoplasmosis in BALB/c mice. Experimental parasitology 17 27059254
2006 MRP-1/CD9 gene transduction regulates the actin cytoskeleton through the downregulation of WAVE2. Oncogene 17 16682943
2023 The cell type dependent sorting of CD9- and CD81 to extracellular vesicles can be exploited to convey tumor sensitive cargo to target cells. Drug delivery 16 36579638
2010 Down-regulation of CD9 expression and its correlation to tumor progression in B lymphomas. The American journal of pathology 16 20566742
2015 Involvement of CD9 and PDGFR in migration is evolutionarily conserved from Drosophila glia to human glioma. Journal of neuro-oncology 15 26224160
2014 Expression of CD9 and CD82 in clear cell renal cell carcinoma and its clinical significance. Pathology, research and practice 15 24553302
2000 Stromal cell CD9 and the differentiation of hematopoietic stem/progenitor cells. Leukemia & lymphoma 15 10811457
1995 Enkephalins stimulate leukemia cell migration and surface expression of CD9. The Journal of clinical investigation 15 7657811

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