Affinage

IGSF8

Immunoglobulin superfamily member 8 · UniProt Q969P0

Length
613 aa
Mass
65.0 kDa
Annotated
2026-06-10
32 papers in source corpus 23 papers cited in narrative 23 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 8/8 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

IGSF8 (EWI-2) is a cell-surface immunoglobulin-superfamily transmembrane protein that organizes tetraspanin-enriched microdomains and couples them to the actin cytoskeleton and downstream receptor signaling (PMID:11504738, PMID:16690612). It forms highly stoichiometric, direct, cross-linkable complexes specifically with the tetraspanins CD9 and CD81 (~70% of CD9/CD81 engaged), an interaction that requires its membrane-distal Ig3-Ig4 domains, a transmembrane glycine-zipper motif, and palmitoylation of juxtamembrane cytoplasmic cysteines (PMID:11504738, PMID:11673522, PMID:21343309). Through these tetraspanins IGSF8 is physically linked to integrins (α3β1, α4β1), and its overexpression reorganizes surface CD81-integrin complexes and suppresses cell spreading, migration, and invasion in a manner dependent on its cytoplasmic tail (PMID:14662754, PMID:15070678). The basic cytoplasmic tail binds ERM proteins and α-actinin and engages phosphatidylinositol phosphates, tethering tetraspanin microdomains to the cytoskeleton at uropods and immune synapses; PIP binding stabilizes the protein while palmitoylation enables tetraspanin association and migration suppression (PMID:16690612, PMID:21609323, PMID:22689882). IGSF8 restrains receptor signaling on multiple axes: it sequesters CD9/CD81 away from TGF-β receptors to limit TGF-β-driven EMT and metastasis (PMID:25656846), prevents EGFR clustering and endocytosis to dampen ERK signaling (PMID:35773608), and promotes lysosomal degradation of growth-factor receptors and integrins via TFEB nuclear retention (PMID:35339615). It localizes to the central supramolecular activation cluster of the T-cell synapse and to HIV virological synapses, where it inhibits Env-mediated cell-cell fusion (PMID:22689882, PMID:31757023). In neurons, IGSF8 acts as a presynaptic organizer of hippocampal mossy-fiber connectivity, controlling bouton filopodia and excitation/inhibition balance (PMID:33057002). As a tumor-expressed ligand it engages the inhibitory NK-cell receptors KIR3DL2 (human) and Klra9 (mouse) to suppress anti-tumor cytotoxicity, and antibody blockade of this interaction enhances NK killing and tumor control (PMID:38657602).

Mechanistic history

Synthesis pass · year-by-year structured walk · 15 steps
  1. 2001 High

    Established the founding molecular fact that IGSF8 is a dedicated, near-stoichiometric direct partner of specific tetraspanins, defining it as a core component of tetraspanin microdomains rather than a promiscuous associate.

    Evidence Co-purification under stringent Brij 96 detergent, mass spectrometry, and chemical cross-linking; domain-deletion mapping with CD81

    PMID:11504738 PMID:11673522

    Open questions at the time
    • No structure of the IGSF8-tetraspanin complex
    • Stoichiometry of higher-order assemblies undefined
  2. 2003 Medium

    Mapped the binding determinants on the tetraspanin side and showed IGSF8 also partners the metastasis suppressor CD82, linking tetraspanin association to suppression of tumor cell migration.

    Evidence Chimeric CD9/CD82 constructs, reciprocal co-IP with cross-linking, hepatocyte co-localization, and migration assays in prostate cancer cells

    PMID:12708969 PMID:12750295

    Open questions at the time
    • Mechanism of migration suppression by IGSF8-CD82 not resolved
    • Single-lab functional assays
  3. 2003 High

    Demonstrated that IGSF8 reorganizes integrin-tetraspanin complexes and that this activity, and surface maturation, depend on CD81 and on the IGSF8 cytoplasmic tail.

    Evidence Overexpression, immunodepletion/reexpression, chimeric and cytoplasmic-tail mutants, migration and shear-flow adhesion assays for α3β1 and α4β1

    PMID:14662754 PMID:15070678

    Open questions at the time
    • Direct vs tetraspanin-bridged contact with integrins not separated
    • Signaling consequences downstream of integrin clustering undefined
  4. 2006 High

    Identified the cytoskeletal coupling mechanism, showing the basic cytoplasmic tail directly binds ERM proteins to tether tetraspanin microdomains to actin and restrain migration and polarity.

    Evidence GST pulldown, co-IP, confocal microscopy, siRNA knockdown, dominant-negative moesin in polarized leukocytes

    PMID:16690612

    Open questions at the time
    • How ERM binding is regulated by activation state unknown
    • Relationship between ERM binding and integrin reorganization unresolved
  5. 2007 Medium

    Proposed IGSF8 as a surface receptor for HSPA8 on dendritic cells with dual effects on migration and antigen presentation, broadening its role beyond tetraspanin scaffolding.

    Evidence Expression cloning, soluble-protein binding assays, dendritic cell migration and stimulation assays

    PMID:17785435

    Open questions at the time
    • Binding site and physiological relevance of HSPA8 engagement unconfirmed
    • Single-lab finding not extended
  6. 2009 Medium

    Defined IGSF8-CD9 complexes in gametes and tested their reproductive role, with conflicting early conclusions about whether IGSF8 controls CD9 surface localization.

    Evidence Stringent detergent co-IP, antibody perturbation in IVF, flow cytometry on CD9-null oocytes

    PMID:19107828 PMID:19210920

    Open questions at the time
    • Apparent dependence of IGSF8 on CD9 later contradicted by knockout data
    • Modest antibody effects on sperm-egg binding hard to interpret
  7. 2009 Medium

    Showed IGSF8 overexpression suppresses glioblastoma colony formation and invasion by tightening CD9/CD81 association and reducing tetraspanin-MMP coupling, generalizing its tumor-suppressive microdomain remodeling.

    Evidence Overexpression in glioma lines, soft agar, motility/invasion assays, co-IP, xenografts

    PMID:19107234

    Open questions at the time
    • Direct effect on MMP activity not measured
    • Single-lab functional data
  8. 2011 High

    Resolved the molecular grammar of tetraspanin binding and connected a proteolytic IGSF8 product to viral entry inhibition, defining the transmembrane and palmitoylation requirements.

    Evidence Mutagenesis of the transmembrane glycine zipper and juxtamembrane palmitoylation cysteines, co-IP, HCV infection assays; PIP-binding lipid assays and palmitoylation assays

    PMID:21343309 PMID:21609323

    Open questions at the time
    • How EWI-2wint cleavage is regulated unknown
    • Distinct contributions of PIP binding vs palmitoylation to in vivo function not fully separated
  9. 2012 High

    Placed IGSF8 at the immune and virological synapse via α-actinin/PIP2-regulated cytoskeletal coupling, where it dampens T-cell IL-2 output and restricts HIV infectivity.

    Evidence Confocal microscopy, mass-spectrometry pulldown identifying α-actinin, siRNA, truncation mutants, IL-2 and HIV infectivity assays; plus olfactory-bulb co-IP and regeneration data

    PMID:22687584 PMID:22689882

    Open questions at the time
    • Direct vs indirect α-actinin contact in vivo unconfirmed
    • Mechanism connecting synapse architecture to cytokine output unresolved
  10. 2012 High

    Genetic knockout established that IGSF8 is dispensable for fertility and not required for CD9 surface localization, correcting an earlier interpretation.

    Evidence Homologous-recombination knockout with in vitro and in vivo fertility testing and immunofluorescence

    PMID:22609062

    Open questions at the time
    • Does not address redundancy with other EWI proteins
    • Reproductive role, if any, remains negative
  11. 2015 High

    Established a defined signaling mechanism: IGSF8 suppresses TGF-β signaling and metastasis by sequestering CD9/CD81 from TGF-β receptors, proven by CD9/CD81-dependent rescue.

    Evidence RNAi, overexpression, co-IP, epistasis via CD9/CD81 blockade, in vitro and in vivo melanoma metastasis assays

    PMID:25656846

    Open questions at the time
    • Quantitative basis of tetraspanin partitioning between receptor pools undefined
    • Generality across other TGF-β receptor contexts untested
  12. 2019 Medium

    Extended the fusion-inhibitory role to the HIV producer cell, showing IGSF8 is downregulated during infection (likely by Vpu) and inhibits Env-mediated cell-cell fusion.

    Evidence Quantitative fluorescence microscopy, shRNA, cell-cell fusion assays

    PMID:31757023

    Open questions at the time
    • Direct mechanism of Vpu-mediated downregulation not demonstrated
    • Single-lab functional data
  13. 2020 High

    Defined a developmental neuronal function: presynaptic IGSF8 organizes mossy-fiber microcircuit architecture and excitation/inhibition balance.

    Evidence MF synaptosome proteomics, cell-surface interactome screening, conditional presynaptic knockout, electrophysiology, electron microscopy

    PMID:33057002

    Open questions at the time
    • Trans-synaptic ligand mediating the organizing activity not pinpointed
    • Relationship to tetraspanin partners in neurons unresolved
  14. 2022 Medium

    Unified IGSF8's receptor-restraining activities, showing it limits EGFR clustering/endocytosis and drives TFEB-dependent lysosomal degradation of growth-factor receptors and integrins to suppress tumor cell proliferation.

    Evidence siRNA/CRISPR ablation, super-resolution imaging of EGFR clustering, endocytosis assays, kinase-inhibitor epistasis, TFEB nuclear-localization and receptor-degradation assays, xenografts

    PMID:35339615 PMID:35773608

    Open questions at the time
    • How IGSF8 signals to TFEB nuclear retention is unknown
    • Direct mechanism preventing EGFR clustering not structurally defined
  15. 2024 High

    Identified IGSF8 as a tumor-expressed innate immune checkpoint engaging inhibitory NK receptors KIR3DL2/Klra9, establishing a therapeutically actionable ligand-receptor axis.

    Evidence CRISPR screens, binding/co-IP, antibody blockade, NK killing assays, syngeneic tumor models with anti-PD1 combination

    PMID:38657602

    Open questions at the time
    • Structural basis of IGSF8-KIR3DL2 recognition not defined
    • Relationship between checkpoint function and tetraspanin scaffolding unexplored

Open questions

Synthesis pass · forward-looking unresolved questions
  • How IGSF8's diverse roles—tetraspanin scaffolding, cytoskeletal coupling, receptor signaling restraint, synaptic organization, and NK checkpoint ligand activity—are integrated by a single protein, and how these are regulated in different cell types, remains unresolved.
  • No structural model of full-length IGSF8 in complex with any partner
  • Whether the extracellular NK-receptor engagement and intracellular tetraspanin/cytoskeleton functions act independently is unknown

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0098772 molecular function regulator activity 3 GO:0008092 cytoskeletal protein binding 2 GO:0060089 molecular transducer activity 2 GO:0008289 lipid binding 1 GO:0048018 receptor ligand activity 1
Localization
GO:0005886 plasma membrane 3 GO:0005856 cytoskeleton 2
Pathway
R-HSA-162582 Signal Transduction 2 R-HSA-1643685 Disease 2 R-HSA-168256 Immune System 2 R-HSA-5653656 Vesicle-mediated transport 2 R-HSA-112316 Neuronal System 1
Partners
ALPHA-ACTININCD81CD82CD9ERM PROTEINSHSPA8ITGA3KIR3DL2
Complex memberships
tetraspanin-enriched microdomain (CD9/CD81/EWI-2)

Evidence

Reading pass · 23 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2001 EWI-2 (IGSF8) was co-purified with tetraspanin CD81 under stringent detergent conditions and identified by mass spectrometry. It associates specifically and directly with CD9 and CD81 (but not other tetraspanins or integrins) in a highly stoichiometric manner (~70% of CD9 and CD81 associated with EWI-2), as confirmed by covalent cross-linking experiments. Co-purification under Brij 96 detergent, mass spectrometry, immunodepletion, chemical cross-linking The Journal of biological chemistry High 11504738
2001 The interaction of CD81 with PGRL (EWI-2/IGSF8) requires the membrane-distal Ig3-Ig4 domains of PGRL, as determined by domain deletion constructs co-expressed with CD81. Co-expression of domain deletion constructs with CD81, immunoprecipitation Journal of immunology Medium 11673522
2003 Two separate regions of CD9 (40 and 47 amino acids) confer the ability to interact with EWI-2, as determined using chimeric CD9/CD82 molecules. EWI-2 was also shown to associate with CD81 on freshly isolated hepatocytes and to co-localize with CD81 in the liver. Chimeric CD9/CD82 protein expression, co-immunoprecipitation, immunofluorescence co-localization The Biochemical journal Medium 12708969
2003 EWI-2/PGRL (IGSF8) physically associates with the metastasis suppressor KAI1/CD82 in a highly stoichiometric, direct complex independent of cholesterol-enriched lipid rafts and distinct from CD81/CD9 complexes. Overexpression of EWI-2/PGRL in Du145 prostate cancer cells inhibits cell migration on fibronectin- and laminin-coated surfaces, and synergizes with KAI1/CD82 in migration suppression. Co-immunoprecipitation, chemical cross-linking, cell migration assays, overexpression Cancer research Medium 12750295
2003 EWI-2 overexpression in A431 cells impairs cell reaggregation and motility on laminin-5 (an alpha3beta1 integrin ligand) but not on collagen I. Tetraspanins CD9 and CD81 physically link EWI-2 to alpha3beta1 integrin. CD81 controls EWI-2 maturation and cell surface localization. A chimeric EWI-2 mutant failed to suppress migration, redirect CD81 to filopodia, or enhance alpha3beta1-CD81 complex formation. Overexpression, immunodepletion, reexpression experiments, cell migration assays, mutagenesis The Journal of cell biology High 14662754
2003 EWI-2 is the most prominent alpha4beta1 integrin partner on MOLT-4 T leukemia cells. Wild-type EWI-2 overexpression markedly impairs cell spreading and ruffling on VCAM-1, while a cytoplasmic tail mutant EWI-2 neither impairs spreading nor associates with alpha4beta1 or CD81. EWI-2 overexpression reorganizes cell-surface CD81, increases CD81-CD81, CD81-alpha4beta1, and alpha4beta1-alpha4beta1 associations, and increases the apparent size of CD81-alpha4beta1 complexes. Anti-integrin antibody bead isolation, mass spectrometry, overexpression, cytoplasmic tail mutagenesis, shear flow adhesion assays, size exclusion chromatography Blood High 15070678
2006 EWI-2 (IGSF8) directly associates with ezrin-radixin-moesin (ERM) proteins through a basic charged amino acid stretch in its cytoplasmic domain. EWI-2 co-localizes with ERM proteins at microspikes, microvilli, and the cellular uropod in polarized leukocytes. Silencing EWI-2 augments cell migration, cellular polarity, and increases ERM phosphorylation. A dominant-negative moesin N-terminal domain delocalizes EWI-2 from the uropod. EWI-2 thereby links tetraspanin microdomains to the actin cytoskeleton. Co-immunoprecipitation, GST pulldown, confocal microscopy, siRNA knockdown, dominant-negative overexpression The Journal of biological chemistry High 16690612
2007 EWI-2/CD316 (IGSF8) functions as a receptor for heat shock protein HSPA8 (hsp70 family member) on human dendritic cells. Soluble EWI-2 bound to cells expressing HSPA8 and to immobilized HSPA8 protein. HSPA8 ligation of EWI-2 enhanced CCL21/SLC-dependent migration of mature dendritic cells but attenuated their antigen-specific stimulatory capacity. Expression cloning, binding assays (soluble protein to cells and immobilized protein), functional migration assays Molecular and cellular biology Medium 17785435
2009 EWI-2 (IGSF8) overexpression in glioblastoma cell lines inhibits colony formation in soft agar and reduces cell motility and invasion. At the biochemical level, EWI-2 causes CD9 and CD81 to become more associated with each other and causes CD81 and other tetraspanins to become less associated with MMP-2 and MT1-MMP. Overexpression in T98G and U87-MG cells, soft agar assay, motility/invasion assays, co-immunoprecipitation, in vivo xenograft Neoplasia Medium 19107234
2009 EWI-2 (IGSF8) forms a direct, stable interaction with CD9 on mouse eggs (stable in 1% Triton X-100). Anti-IgSF8 antibody has moderate inhibitory effects on sperm-egg binding, whereas anti-CD9 antibody significantly inhibits sperm-egg fusion, indicating that IgSF8 and CD9 have discrete, non-identical functions in gamete interaction. Detergent co-immunoprecipitation, antibody perturbation in IVF assays Reproduction, fertility, and development Medium 19210920
2009 On CD9-null oocytes, surface EWI-2 expression is reduced to <10% of wild-type levels, indicating that CD9 is required for normal surface localization of EWI-2. Depalmitoylated CD9 mutant does not affect EWI-2 surface levels, showing that CD9 palmitoylation is not required for maintaining EWI-2 at the surface. Flow cytometry on CD9 knockout oocytes, depalmitoylation mutant analysis Molecular reproduction and development Medium 19107828
2011 A glycine zipper motif in the transmembrane domain of EWI-2/EWI-2wint is essential for interaction with CD81. Palmitoylation on two juxtamembranous cysteines in the cytosolic tail of EWI-2/EWI-2wint is required for interaction with both CD81 and CD9. EWI-2wint (a proteolytic cleavage product of EWI-2) must interact with CD81 to exert its inhibitory effect on HCV infection. Mutagenesis of transmembrane glycine zipper and cytoplasmic cysteine residues, co-immunoprecipitation, HCV infection functional assays The Journal of biological chemistry High 21343309
2011 The EWI-2 cytoplasmic tail specifically interacts with negatively charged phosphatidylinositol phosphates (PIPs), particularly PtdIns5P, PtdIns4P, and PtdIns3P, but not other membrane lipids. Mutation of either of two basic residue clusters abolishes PIP binding. EWI-2 is constitutively palmitoylated at cytoplasmic cysteine residues. PIP binding regulates EWI-2 protein stability, while palmitoylation is required for tetraspanin-EWI-2 association and EWI-2-dependent inhibition of cell migration and lamellipodia formation. Lipid binding assays, site-directed mutagenesis of basic residue clusters and cysteines, palmitoylation assays, cell migration assays The Biochemical journal High 21609323
2012 EWI-2 co-localizes with CD3 and CD81 at the central supramolecular activation cluster (cSMAC) of the T cell immune synapse. Mass spectrometry of pull-downs with the C-terminal intracellular domain of EWI-2 identified α-actinin as a specific binding partner; this association is regulated by PIP2. Silencing EWI-2 or overexpression of a cytoplasmic-truncated EWI-2 mutant increases IL-2 secretion upon antigen stimulation. Silencing EWI-2 or α-actinin-4 increases HIV cell infectivity at virological synapses. Confocal microscopy, mass spectrometry pull-down, siRNA knockdown, overexpression of truncation mutant, IL-2 secretion assay, HIV infectivity assay Journal of immunology High 22689882
2012 IGSF8 (EWI-2) interacts with tetraspanin CD9 in the olfactory bulb. Both IgSF8 and CD9 localize to puncta within axons and growth cones of olfactory sensory neurons, consistent with tetraspanin-enriched microdomain localization. IgSF8 expression in synaptic neuropil is transitory during glomerular formation and re-appears upon OSN regeneration, consistent with a role in synapse formation. Co-immunoprecipitation from olfactory bulb tissue, immunofluorescence, in vivo lesion/regeneration experiments Molecular and cellular neurosciences Medium 22687584
2012 Igsf8-deficient female mice show no fertilization defect in vitro or in vivo. Igsf8-deficient eggs retain normal CD9 levels and localization with normal microvilli formation, indicating IGSF8 is dispensable for fertility and not required for CD9 surface localization (contrary to a previous suggestion). Homologous recombination knockout, in vitro and in vivo fertility testing, immunofluorescence Fertility and sterility High 22609062
2015 EWI-2 (IGSF8) negatively regulates TGF-β signaling in melanoma. When EWI-2 is present, it sequesters CD9 and CD81 away from TGF-β receptors. When EWI-2 is knocked down, CD9 and CD81 become available to support TβR2-TβR1 association, elevating TGF-β signaling and downstream cytostasis, EMT-like changes, CD271-dependent invasion, and lung metastasis. All EWI-2 depletion phenotypes are reversed by blocking or depleting CD9 or CD81. RNAi knockdown, overexpression, co-immunoprecipitation, in vitro and in vivo functional assays, epistasis by CD9/CD81 blocking Cell research High 25656846
2019 EWI-2 accumulates at the presynaptic terminal (producer cell side) of the HIV virological synapse and contributes to inhibition of Env-mediated cell-cell fusion. EWI-2 is downregulated upon HIV-1 infection, likely by Vpu. EWI-2 and CD81 surface levels are restored on syncytia where they continue to act as fusion inhibitors. Quantitative fluorescence microscopy, shRNA knockdown, cell-cell fusion assays Viruses Medium 31757023
2020 IgSF8 is a neuronal receptor enriched in the hippocampal mossy fiber (MF) pathway. Presynaptic Igsf8 deletion impairs MF synaptic architecture and robustly decreases the density of bouton filopodia that provide feedforward inhibition. IgSF8 loss impairs excitation/inhibition balance and increases excitability of CA3 pyramidal neurons. Cell-surface interactome screening identified IgSF8 interaction partners at the MF synapse. MF synaptosome proteomic profiling, cell-surface interactome screening, conditional presynaptic knockout, electrophysiology, electron microscopy Nature communications High 33057002
2021 EWI-2 (IGSF8) localizes not only on the plasma membrane but also on the nuclear envelope, where it regulates nuclear translocation of EGFR-MAPK-ERK signaling molecules and sorting of miR-3934-5p between cells and exosomes, thereby regulating prostate cancer cell metastasis. Subcellular fractionation, immunofluorescence, exosome isolation, miRNA quantification, signaling pathway analysis Molecular oncology Low 33605506
2022 EWI2 (IGSF8) prevents EGFR from clustering and endocytosis, thereby restraining EGFR activation and ERK MAP kinase signaling. Upon EWI2 silencing or ablation, EGFR clustering, endocytosis, and activation increase, leading to enhanced cancer cell proliferation and migration. Inhibition of EGFR or ERK kinase abrogates the phenotypes caused by EWI2 removal. siRNA knockdown, CRISPR ablation, super-resolution microscopy (EGFR clustering), endocytosis assays, kinase inhibitor epistasis, in vivo xenograft Cellular and molecular life sciences Medium 35773608
2022 EWI2 (IGSF8) promotes endolysosomal trafficking and lysosomal degradation of growth factor receptors and integrins by promoting nuclear retention of the master transcription factor TFEB, thereby driving lysosomogenesis and reducing surface levels of these receptors in lung cancer cells. Forced overexpression, lysosomal trafficking assays, TFEB nuclear localization experiments, receptor degradation assays, in vivo tumor models Cancer letters Medium 35339615
2024 IGSF8 expressed on tumors suppresses NK cell function by directly interacting with human KIR3DL2 and mouse Klra9 inhibitory receptors on NK cells. An antibody blocking IGSF8-NK receptor interaction enhances NK cell killing of malignant cells in vitro and upregulates antigen presentation, NK cell-mediated cytotoxicity, and T cell signaling in vivo. Anti-IGSF8 alone or combined with anti-PD1 inhibits tumor growth in syngeneic models. CRISPR screens, co-immunoprecipitation/binding assays, antibody blockade, NK cell killing assays, in vivo syngeneic tumor models Cell High 38657602

Source papers

Stage 0 corpus · 32 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2001 EWI-2 is a major CD9 and CD81 partner and member of a novel Ig protein subfamily. The Journal of biological chemistry 190 11504738
2006 EWI-2 and EWI-F link the tetraspanin web to the actin cytoskeleton through their direct association with ezrin-radixin-moesin proteins. The Journal of biological chemistry 165 16690612
2003 EWI-2 is a new component of the tetraspanin web in hepatocytes and lymphoid cells. The Biochemical journal 117 12708969
2003 EWI2/PGRL associates with the metastasis suppressor KAI1/CD82 and inhibits the migration of prostate cancer cells. Cancer research 88 12750295
2001 PGRL is a major CD81-associated protein on lymphocytes and distinguishes a new family of cell surface proteins. Journal of immunology (Baltimore, Md. : 1950) 74 11673522
2003 EWI-2 regulates alpha3beta1 integrin-dependent cell functions on laminin-5. The Journal of cell biology 72 14662754
2003 EWI-2 modulates lymphocyte integrin alpha4beta1 functions. Blood 51 15070678
2011 Interacting regions of CD81 and two of its partners, EWI-2 and EWI-2wint, and their effect on hepatitis C virus infection. The Journal of biological chemistry 50 21343309
2015 EWI-2 negatively regulates TGF-β signaling leading to altered melanoma growth and metastasis. Cell research 48 25656846
2020 Synapse type-specific proteomic dissection identifies IgSF8 as a hippocampal CA3 microcircuit organizer. Nature communications 45 33057002
2012 EWI-2 association with α-actinin regulates T cell immune synapses and HIV viral infection. Journal of immunology (Baltimore, Md. : 1950) 44 22689882
2024 IGSF8 is an innate immune checkpoint and cancer immunotherapy target. Cell 43 38657602
2009 Glioblastoma inhibition by cell surface immunoglobulin protein EWI-2, in vitro and in vivo. Neoplasia (New York, N.Y.) 42 19107234
2009 Immunoglobulin superfamily member IgSF8 (EWI-2) and CD9 in fertilisation: evidence of distinct functions for CD9 and a CD9-associated protein in mammalian sperm-egg interaction. Reproduction, fertility, and development 32 19210920
2021 EWI-2 controls nucleocytoplasmic shuttling of EGFR signaling molecules and miRNA sorting in exosomes to inhibit prostate cancer cell metastasis. Molecular oncology 21 33605506
2007 EWI-2/CD316 is an inducible receptor of HSPA8 on human dendritic cells. Molecular and cellular biology 20 17785435
2012 Tetraspanin-interacting protein IGSF8 is dispensable for mouse fertility. Fertility and sterility 17 22609062
2015 Novel impact of EWI-2, CD9, and CD81 on TGF-β signaling in melanoma. Molecular & cellular oncology 16 26989766
2011 Differential functions of phospholipid binding and palmitoylation of tumour suppressor EWI2/PGRL. The Biochemical journal 16 21609323
2012 IgSF8: a developmentally and functionally regulated cell adhesion molecule in olfactory sensory neuron axons and synapses. Molecular and cellular neurosciences 15 22687584
2019 EWI-2 Inhibits Cell-Cell Fusion at the HIV-1 Virological Presynapse. Viruses 13 31757023
2009 Loss of surface EWI-2 on CD9 null oocytes. Molecular reproduction and development 12 19107828
2023 EWI2 and its relatives in Tetraspanin-enriched membrane domains regulate malignancy. Oncogene 11 36788350
2003 Genomic organization and embryonic expression of Igsf8, an immunoglobulin superfamily member implicated in development of the nervous system and organ epithelia. Molecular and cellular neurosciences 10 12595239
2022 EWI2 prevents EGFR from clustering and endocytosis to reduce tumor cell movement and proliferation. Cellular and molecular life sciences : CMLS 8 35773608
2022 EWI2 promotes endolysosome-mediated turnover of growth factor receptors and integrins to suppress lung cancer. Cancer letters 6 35339615
2024 IGSF8 is a potential target for the treatment of gliomas. Asian journal of surgery 5 38453613
2017 Differential expression of EWI-2 in endometriosis, its functional role and underlying molecular mechanisms. The journal of obstetrics and gynaecology research 4 28544021
2025 IGSF8 impairs migration and invasion of trophoblast cells and angiogenesis in preeclampsia. Experimental cell research 2 39755227
1991 Thymic origin of some natural killer cells: clonal proliferation of human CD3-16+ cells from CD3-4-8- thymocyte precursors requires the presence of H9 leukemic cells. International journal of clinical & laboratory research 1 1840028
2025 Functional characterization and clinical significance of IGSF8 in pan-cancer: an integrated bioinformatic and experimental study. Frontiers in immunology 0 40936932
2025 R3HDM4 influences kidney renal clear cell carcinoma progression, immune modulation, and potential links to the IGSF8 immune checkpoint. Frontiers in immunology 0 41346582

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