Affinage

Showing LY6E — TSA-1 is a alias.

LY6E

Lymphocyte antigen 6E · UniProt Q16553

Length
131 aa
Mass
13.5 kDa
Annotated
2026-06-10
73 papers in source corpus 29 papers cited in narrative 28 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

LY6E is an interferon-inducible, GPI-anchored cell-surface protein of the Ly-6 family that acts as a bidirectional modulator of viral entry by targeting the membrane fusion step (PMID:30190477, PMID:32704094, PMID:32511345, PMID:40901862). Against coronaviruses it is a potent restriction factor, blocking spike protein-mediated membrane fusion at both endosomal and plasma membranes through a mechanism distinct from IFITM3, and was identified by focused CRISPR screening as the key GPI-anchored effector of the GPI-biosynthesis antiviral pathway (PMID:32704094, PMID:32511345, PMID:32641482, PMID:40901862). Conditional knockout across multiple lineages established Ly6e as a pan-coronavirus restriction factor that protects respiratory epithelial and immune cells in vivo (PMID:37443277). Conversely, LY6E enhances entry of influenza A virus, yellow fever virus, alphaviruses and HIV-1 by promoting post-endosomal uncoating or membrane fusion, with a single loop residue required for the enhancing activity (PMID:30190477, PMID:28130445); its effect on HIV-1 is CD4-level-dependent, restricting entry in low-CD4 cells by driving CD4 internalization while enhancing fusion when CD4 is abundant (PMID:28130445, PMID:30674630). Beyond virology, LY6E serves as the receptor for the retroviral fusogen Syncytin-A and is essential for syncytiotrophoblast layer I cell-cell fusion in the placenta, its loss causing embryonic lethality of placental origin (PMID:28679758, PMID:29500366). LY6E also dampens innate and adaptive immune signaling: it downregulates CD14 to limit LPS responsiveness via a LY6E-PHB1-TRIM21 ubiquitin-proteasome axis (PMID:25225669, PMID:37250795), inhibits TCR-induced IL-2 production by reducing CD3 zeta-chain phosphorylation through its extracellular domain independently of the GPI anchor (PMID:7499840, PMID:8051400), and modulates NLRP3 inflammasome and STING-dependent IL-1β production in macrophages (PMID:40114200). In cancer, LY6E promotes tumor growth and angiogenesis through a PTEN/PI3K/Akt/HIF-1 axis and supports TGFβ/Smad signaling and EMT (PMID:27589564, PMID:27197181, PMID:34994389). Its expression is IFN-driven through defined chromatin regulatory elements and is post-transcriptionally stabilized by NAT10-mediated ac4C modification of its mRNA during alphavirus infection (PMID:38169284, PMID:8639891, PMID:10395674).

Mechanistic history

Synthesis pass · year-by-year structured walk · 15 steps
  1. 1986 Medium

    Established the basic biochemical identity of the protein as a small, disulfide-bonded, non-N-glycosylated cell-surface antigen, providing the structural baseline before any functional role was known.

    Evidence Immunoprecipitation, SDS-PAGE, tunicamycin treatment and gel filtration of radiolabeled murine Ly-6E.1

    PMID:3941270

    Open questions at the time
    • No functional activity assigned
    • GPI anchor not yet demonstrated
    • Single ortholog characterized
  2. 1989 High

    Defined how LY6E is targeted to the membrane, showing two C-terminal signal regions are necessary for GPI biosynthesis and attachment.

    Evidence C-terminal deletion and site-directed mutagenesis in COS cells with secretion versus membrane-retention readouts

    PMID:2796989

    Open questions at the time
    • Functional consequence of GPI anchoring not addressed
    • No link to downstream signaling or viral roles
  3. 1995 High

    Resolved that LY6E modulates TCR signaling through its extracellular domain rather than its GPI anchor, by reducing CD3 zeta-chain phosphorylation and IL-2 production.

    Evidence Anti-TSA-1 antibody treatment and GPI-versus-transmembrane chimeric constructs in T cells and Jurkat, with IL-2 and phospho-zeta readouts (also #14)

    PMID:7499840 PMID:8051400

    Open questions at the time
    • Direct binding partner transducing the inhibitory signal not identified
    • Physiological relevance to T-cell responses in vivo not established
  4. 1996 Medium

    Mapped the cis-regulatory architecture and trans-acting factors driving IFN-inducible LY6E expression, explaining why it behaves as an interferon-stimulated gene.

    Evidence Promoter/enhancer deletion constructs, DNase I hypersensitive site mapping, EMSA and antisense HMGI-C inhibition with IFN induction assays (also #26, #27)

    PMID:10395674 PMID:1692061 PMID:8639891

    Open questions at the time
    • Human regulatory elements not directly mapped
    • Connection between IFN induction and antiviral function not yet made
  5. 2017 High

    Identified LY6E as the cellular receptor for the retroviral fusogen Syncytin-A, linking the protein to physiological cell-cell fusion.

    Evidence cDNA library functional screen, siRNA knockdown and soluble-ectodomain competition in cell-cell fusion assays

    PMID:28679758

    Open questions at the time
    • Structural basis of the LY6E-SynA interaction not defined
    • Whether the same surface mediates viral entry enhancement unknown
  6. 2017 High

    Demonstrated that LY6E enhances HIV-1 infection at the membrane fusion step and additionally boosts LTR-driven gene expression, framing it as a proviral factor.

    Evidence RNAi knockdown across PBMCs, SupT1 and THP-1, fusion assays, LTR-reporter and replication assays

    PMID:28130445

    Open questions at the time
    • Molecular mechanism of fusion enhancement not defined
    • Reconciliation with restrictive contexts not yet established
  7. 2018 High

    Showed LY6E enhances diverse RNA virus infections by acting after endosomal escape at the uncoating step, and pinpointed a single loop residue essential for enhancement, defining its proviral mechanism.

    Evidence Ectopic expression, influenza A uncoating assays, structure-function mutagenesis and ortholog testing

    PMID:30190477

    Open questions at the time
    • Direct molecular target during uncoating unidentified
    • How a surface GPI protein acts post-endosomally is unresolved
  8. 2018 High

    Established the physiological essentiality of LY6E in placental syncytiotrophoblast layer I fusion, with tissue-specific knockouts localizing embryonic lethality to the placenta.

    Evidence Global, epiblast-specific and placenta-specific Ly6e knockout mice with histological analysis (also #8)

    PMID:23830620 PMID:29500366

    Open questions at the time
    • Mechanism connecting receptor engagement to fusion machinery not detailed
    • Human placental requirement not directly tested
  9. 2019 High

    Reconciled LY6E's opposing effects on HIV-1 by showing they are CD4-level-dependent: in low-CD4 cells it restricts entry by internalizing CD4, whereas in high-CD4 cells it enhances fusion.

    Evidence Knockdown/overexpression in Jurkat and MDMs, CD4 colocalization and internalization assays, and CD4 manipulation

    PMID:30674630

    Open questions at the time
    • How LY6E triggers CD4 internalization mechanistically unclear
    • Generalizability to primary infection settings not fully tested
  10. 2020 High

    Defined LY6E as a potent coronavirus restriction factor that blocks spike-mediated fusion, distinct from IFITM3, and demonstrated in vivo protection using conditional knockout mice.

    Evidence Gain/loss-of-function in multiple cell lines, spike fusion assays, IFITM3 comparison, and conditional KO mice in CoV infection models (also #2)

    PMID:32511345 PMID:32641482 PMID:32704094

    Open questions at the time
    • Molecular mechanism by which a GPI protein blocks fusion not resolved
    • Why LY6E restricts CoV but enhances other viruses unexplained
  11. 2023 High

    Generalized LY6E to a pan-coronavirus respiratory restriction factor and identified the protective cell lineages, showing it shields club and ciliated cells and preserves the lung epithelial transcriptome.

    Evidence Seven conditional Ly6e knockout mouse lines with murine CoV and SARS-CoV-2 infection plus lung transcriptomics

    PMID:37443277

    Open questions at the time
    • Cell-intrinsic fusion-blocking mechanism still undefined
    • Relative contribution of each lineage to overall protection not quantified
  12. 2023 High

    Elucidated the molecular machinery of LY6E-mediated CD14 downregulation, identifying a LY6E-PHB1-TRIM21 ubiquitin-proteasome assembly.

    Evidence Interactome MS, co-immunoprecipitation, proteasome inhibition and ubiquitination assays with TRIM21 manipulation (also #9)

    PMID:25225669 PMID:37250795

    Open questions at the time
    • How a surface GPI protein nucleates a cytoplasmic E3 ligase complex unclear
    • Breadth of LY6E-PHB1-TRIM21 substrates beyond CD14 unknown
  13. 2024 Medium

    Identified post-transcriptional control of LY6E, showing NAT10-mediated ac4C of its 3'-UTR stabilizes the mRNA and supports translation during alphavirus infection.

    Evidence NAT10 knockdown/inhibition, ac4C mapping, mRNA stability assays and LY6E rescue in SINV replication

    PMID:38169284

    Open questions at the time
    • Whether ac4C regulation operates in other infection contexts untested
    • Single lab, epitranscriptomic site mapping not orthogonally confirmed
  14. 2025 High

    Positioned LY6E as the key downstream effector of a conserved GPI-biosynthesis antiviral pathway against multiple coronaviruses, unifying genetic screen and fusion-block findings.

    Evidence Genome-wide and focused CRISPR KO screens of 193 GPI-APs across three coronaviruses with fusion assays

    PMID:40901862

    Open questions at the time
    • Direct biochemical step of fusion inhibition still not defined
    • Why only LY6E among GPI-APs is the effector not fully explained
  15. 2025 Medium

    Extended LY6E into inflammasome and metastasis biology, showing it modulates NLRP3/STING-driven IL-1β in macrophages and is transcriptionally activated by a nuclear PD-L1/POLR2A complex driving TNBC metastasis.

    Evidence Primary macrophage pathway assays with kidney colocalization (#21) and CRISPR PD-L1 ablation with ChIP-seq, Co-IP and in vivo metastasis (#22)

    PMID:40114200 PMID:41388312

    Open questions at the time
    • Direct molecular link between LY6E and inflammasome components not defined
    • Single-lab findings without independent replication

Open questions

Synthesis pass · forward-looking unresolved questions
  • The unifying biochemical mechanism explaining how a single GPI-anchored protein both blocks coronavirus fusion and enhances fusion/uncoating of other enveloped viruses remains unresolved.
  • No structure of LY6E or its viral-protein interfaces
  • Direct molecular partners at the fusion membrane unidentified
  • Determinants dictating restriction versus enhancement undefined

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0098772 molecular function regulator activity 4 GO:0060089 molecular transducer activity 3 GO:0001618 virus receptor activity 2
Localization
GO:0005886 plasma membrane 4
Pathway
R-HSA-168256 Immune System 4 R-HSA-162582 Signal Transduction 3 R-HSA-1643685 Disease 3 R-HSA-1266738 Developmental Biology 2
Partners
CD14CD4CHRNA5PHB1POLR2ASYNCYTIN-ATRIM21
Complex memberships
LY6E-PHB1-TRIM21 assembly

Evidence

Reading pass · 28 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2018 LY6E is a GPI-anchored, IFN-inducible cell surface protein that enhances infection by multiple RNA viruses (influenza A, HIV, yellow fever virus) by promoting viral entry. Using influenza A virus as a model, the enhancing effect was narrowed to uncoating after endosomal escape. Structure-function analyses identified a single amino acid in a predicted loop region essential for viral enhancement. Diverse mammalian orthologs also enhance viral infectivity, indicating evolutionary conservation. Ectopic expression in multiple cell lines, influenza A virus uncoating assays, structure-function mutagenesis, ortholog testing Nature communications High 30190477
2020 LY6E potently restricts infection by multiple coronaviruses (SARS-CoV, SARS-CoV-2, MERS-CoV) by interfering with spike protein-mediated membrane fusion during viral entry. Mice lacking Ly6e in immune cells were highly susceptible to murine CoV (MHV), with loss of hepatic immune cells, higher splenic viral burden, and reduction in global antiviral gene pathways. Constitutive Ly6e directly protects primary B cells from murine CoV infection. Ectopic expression/knockdown assays, spike protein-mediated fusion assays, conditional knockout mice (Ly6e deleted in hematopoietic cells), in vivo murine CoV infection model Nature microbiology High 32511345 32704094
2020 LY6E restricts HCoV-OC43 entry and the entry mediated by spike proteins of other human coronaviruses including SARS-CoV-2. Overexpression of TMPRSS2 or amphotericin treatment (which overcomes IFITM3 restriction) did not compromise LY6E's effect on CoV entry, indicating a mechanism distinct from IFITM3. Ectopic expression in HEK293, C3A, and A549 cells; LY6E knockdown in HepG2; spike-pseudovirus entry assays; comparison with TMPRSS2 overexpression and amphotericin treatment Journal of virology High 32641482
2023 Ly6e is a pan-coronavirus restriction factor in the respiratory tract. Using conditional Ly6e knockout mice (seven different Cre lines), Ly6e expression in Lyz2-expressing cells, radioresistant Vav1-expressing cells, and non-haematopoietic cells conferred control of murine coronavirus and SARS-CoV-2. Ly6e protected secretory club and ciliated cells from SARS-CoV-2 infection and prevented virus-induced loss of an epithelial cell transcriptomic signature in the lung. Panel of seven conditional Ly6e knockout mouse lines, murine coronavirus and SARS-CoV-2 infection models, transcriptomic profiling of lung Nature microbiology High 37443277
2017 LY6E promotes HIV-1 infection by enhancing viral membrane fusion at the entry step. Additionally, LY6E enhances LTR-driven HIV-1 gene expression. Knockdown of LY6E in PBMCs, SupT1, and THP-1 cells diminishes HIV-1 replication. HIV-1 infection itself induces LY6E expression concomitant with type I IFN production. LY6E knockdown (RNAi) in multiple cell lines, virion-cell and cell-cell fusion assays, LTR-reporter assay, HIV-1 replication assays The Journal of biological chemistry High 28130445
2019 In low-CD4-expressing cells (Jurkat, MDMs), LY6E inhibits HIV-1 entry and spread by downregulating cell surface CD4 via enhanced CD4 internalization. LY6E colocalizes with CD4 on the plasma membrane. Artificially raising CD4 in Jurkat cells overcomes LY6E inhibition; blocking CD4 in SupT1 eliminates LY6E enhancement. Thus LY6E's effect on HIV-1 entry is CD4-level-dependent. LY6E knockdown and overexpression in Jurkat and MDMs, colocalization by microscopy, CD4 internalization assay, CD4 manipulation (overexpression and neutralizing antibody), HIV-1 entry assays Journal of virology High 30674630
2017 LY6E (Ly6e) is identified as the receptor for mouse endogenous retroviral fusogenic protein Syncytin-A (SynA). Cell-cell fusion assay with cDNA library screening identified Ly6e as a GPI-anchored membrane protein sufficient to mediate SynA-induced cell fusion. siRNA knockdown of Ly6e greatly reduced SynA-induced fusion. Competition with soluble ectodomain of Ly6e confirmed direct interaction. No cross-reactive fusion with Syncytin-B was detected. Cell-cell fusion assay combined with cDNA library screening, transfection rescue, siRNA knockdown, competition assay with soluble Ly6e ectodomain Journal of virology High 28679758
2018 Ly6e is essential for syncytiotrophoblast layer I (ST-I) fusion in the mouse placenta. Ly6e knockout causes embryonic lethality due to failure of syncytiotrophoblast layer I cell-cell fusion and defects in both fetal and maternal vasculature morphogenesis. Epiblast-specific (but not placenta-specific) Ly6e inactivation is compatible with embryonic development, indicating lethality is placental in origin. Ly6e global knockout mice, epiblast-specific and placenta-specific conditional Ly6e knockout, histological and morphological analysis of placenta Scientific reports High 29500366
2013 Ly6e mRNA is expressed in syncytiotrophoblast cells of the mouse placenta labyrinth, with expression correlating spatially with Syncytin-A. LY6E+ cells express Syncytin-A at higher levels than LY6E- cells. Expression increases with trophoblast differentiation. mRNA in situ hybridization, Northern blot, FACS isolation of LY6E+ cells, RT-PCR Placenta Medium 23830620
2014 LY6E in monocytes negatively modulates CD14 expression and dampens responsiveness to LPS stimulation. In the setting of chronic HIV infection, upregulation of LY6E correlates with reduced CD14 levels on monocytes, but the immunosuppressive effect is insufficient to remedy hyperactivation. LY6E knockdown/overexpression in monocytic cells, LPS stimulation assays, CD14 expression measurement, correlation with chronic HIV patient samples Journal of immunology Medium 25225669
2023 LY6E downregulates CD14 via ubiquitin-dependent proteasomal degradation. The LY6E protein interactome identified PHB1, which interacts with CD14 in a LY6E-dependent manner. TRIM21 was identified as the major ubiquitin E3 ligase mediating LY6E-dependent ubiquitination of CD14, forming a LY6E-PHB1-TRIM21 assembly. Proteasome inhibitor assays, LY6E interactome profiling (MS), co-immunoprecipitation, TRIM21 knockdown/overexpression, ubiquitination assays iScience High 37250795
2016 LY6E activates HIF-1 transcription principally at the transcriptional level, leading to upregulation of VEGFA and PDGFB. This occurs through decreased PTEN mRNA expression and subsequent activation of the PI3K/Akt pathway. The LY6E-HIF-1 axis increases tumor blood vessel density and promotes tumor growth in immunodeficient mice. LY6E overexpression/knockdown, HIF-1α reporter and mRNA analysis, PTEN/PI3K/Akt pathway analysis, in vivo xenograft tumor growth and angiogenesis assay Oncotarget Medium 27589564
2016 LY6E is required for TGFβ signaling and proliferation in breast cancer cells, contributing to phosphorylation of Smad1/5 and Smad2/3. LY6E also promotes cytokine-induced PDL1 expression and modulates NK cell binding to cancer cells, and promotes drug resistance. LY6E knockdown in breast cancer cell lines, TGFβ/Smad phosphorylation assays, PDL1 expression assays, NK cell co-culture assays, drug resistance assays Cancer research Medium 27197181
1995 TSA-1/Sca-2 (murine LY6E ortholog) is a GPI-anchored protein that modulates TCR-mediated signaling. Anti-TSA-1 inhibits IL-2 production from T cells stimulated with anti-CD3, reducing CD3 zeta-chain tyrosine phosphorylation. This inhibitory function does not require the GPI anchor, as a transmembrane form of TSA-1 retains inhibitory activity. Anti-TSA-1 antibody treatment of normal T cells and T cell hybridomas, transfection of Jurkat cells with GPI-anchored and transmembrane TSA-1 constructs, IL-2 assay, tyrosine phosphorylation of CD3 zeta by Western blot Journal of immunology High 7499840
1994 Cross-linking of Ly-6E on T lymphocytes inhibits anti-CD3-induced IL-2 production. Both GPI-anchored and transmembrane forms of Ly-6E (chimeric construct with H-2Db transmembrane/cytoplasmic domain) mediate inhibition of IL-2 production, indicating the inhibitory signaling depends on the extracellular domain and not the GPI anchor. The Ly-6 inhibitory pathway is operative in human cells (Jurkat). Transfection of EL-4J cells with Ly-6 proteins, GPI-to-transmembrane chimeric Ly-6E construct, IL-2 production assays, cross-species functional assay in Jurkat cells Journal of immunology Medium 8051400
1989 LY6E (Ly-6E/A) is a GPI-anchored cell surface protein. Deletion of 12 or 20 C-terminal residues abolishes GPI modification and results in secretion of the protein. Addition of the LFA-3 cytoplasmic tail to the C-terminus partially inhibits GPI addition. Mutation of an Asn residue at the hypothetical cleavage site alters GPI attachment site usage. Two C-terminal regions act as necessary signals for GPI biosynthesis. C-terminal deletion mutagenesis, site-directed mutagenesis, COS cell transient transfection, radiolabeling, SDS-PAGE analysis of secretion vs. membrane retention Molecular and cellular biology High 2796989
2024 NAT10-mediated ac4C (N4-acetylcytidine) modification of LY6E mRNA at its 3'-UTR is required for LY6E mRNA stability and efficient translation during alphavirus (Sindbis virus) infection. NAT10 is upregulated after alphavirus infection, and loss of NAT10 or inhibition of its acetyltransferase activity reduces alphavirus replication by destabilizing LY6E mRNA. NAT10 knockdown/inhibition, ac4C modification mapping (acRIP-seq or similar), mRNA stability assays, LY6E overexpression rescue, SINV replication assays Journal of virology Medium 38169284
2025 GPI biosynthesis pathway acts as a conserved host restriction mechanism against multiple coronaviruses (SARS-CoV-2, HCoV-OC43, PEDV) by disrupting spike protein-mediated membrane fusion at both endosomal and plasma membranes. Focused CRISPR KO screen of 193 GPI-anchored proteins identified LY6E as the key downstream effector of GPI biosynthesis antiviral activity. Genome-wide CRISPR KO screens with three coronaviruses, focused CRISPR KO screen of 193 GPI-APs, fusion assays PLoS pathogens High 40901862
2022 LY6E associates with α5-nAChR and mediates TGF-β1/Smad signaling (specifically pSmad3) and EMT marker expression in non-small cell lung cancer. Silencing both α5-nAChR and LY6E inhibits cell migration more effectively than silencing either alone. α5-nAChR mediates LY6E expression as well as Zeb1, N-cadherin and vimentin expression. siRNA knockdown of LY6E and α5-nAChR, Western blot for pSmad3 and EMT markers, cell migration assays, CAM model, mouse xenograft Carcinogenesis Medium 34994389
1986 The murine Ly-6E.1 protein is a ~17-18 kDa cell surface antigen with intrachain but not interchain disulfide bonds, does not carry N-linked carbohydrate (tunicamycin-insensitive), and exists as two polypeptide forms. The native molecule behaves as a single polypeptide chain rather than a dimer. In the presence of deoxycholate it elutes as ~31 kDa on gel filtration, consistent with detergent association. Immunoprecipitation from biosynthetically radiolabeled cells, SDS-PAGE (reduced and non-reduced), tunicamycin treatment, pulse-chase, gel filtration, isoelectric focusing Journal of immunology Medium 3941270
2022 LY6E facilitates AAV-PHP.eB crossing of the human blood-brain barrier in vitro. RNAi knockdown of LY6E and capsid protein binding assays demonstrated that AAV-PHP.eB delivery across the BBB is mediated by LY6E. Biomimetic BBB chip model, RNAi knockdown of LY6E, virus capsid protein binding assay, AAV crossing efficiency assay Lab on a chip Medium 36165190
2025 LY6E regulates IFN-α- and immune complex-induced production of mature IL-1β in macrophages. LY6E modulates NLRP3 inflammasome activation, caspase-1 activation, STING pathway, mitochondrial ROS generation, and CMPK2 activation. LY6E also modulates foam cell formation. LY6E colocalizes with macrophage marker in kidneys from lupus-prone mice and lupus nephritis patients. Bone marrow-derived macrophage culture with LY6E manipulation, NLRP3/caspase-1 activation assays, mtDNA release assay, mtROS measurement, STING pathway assays, CMPK2 activity assay, foam cell assay, immunofluorescence colocalization in kidney tissue Cell communication and signaling Medium 40114200
2025 Nuclear PD-L1 transcriptionally activates LY6E expression by binding to RNA polymerase II subunit POLR2A, forming a transcriptional complex that directly drives LY6E promoter activity. This nuclear PD-L1/POLR2A-LY6E axis promotes IFN-γ-driven lung metastasis of triple-negative breast cancer. CRISPR/Cas9 PD-L1 ablation, RNA-seq, ChIP-seq (nuclear PD-L1 binding), co-immunoprecipitation of PD-L1 and POLR2A, in vivo metastasis assays Breast cancer research Medium 41388312
2003 Chicken LY6E (SCA2/TSA1) specifically interacts with MDV protein US10, as identified in a bacterial two-hybrid screen and confirmed by in vitro protein-binding assay. LY6E was significantly associated with Marek's disease resistance traits in a commercial chicken population. E. coli two-hybrid screen, in vitro protein-binding assay, linkage analysis in MD resource population Cytogenetic and genome research Low 14970721
1994 Mouse Sca-2 (Ly6E ortholog) is a member of the Ly-6 family anchored in the membrane by a GPI moiety, as determined from full-length cDNA sequence from thymocytes. cDNA cloning and sequence analysis, GPI anchor prediction PNAS Medium 8202484
1996 High-level IFN-gamma-induced expression of the Ly-6E.1 gene in hematopoietic cells requires a 3' chromatin-dependent region containing DNase I hypersensitive sites at +8.7 and +8.9 kb, which contains a consensus gamma-IFN-responsive element. Both 5' and 3' hypersensitive sites are rapidly induced with IFN-gamma. Deletion constructs of Ly-6E.1 flanking regions, transfection in hematopoietic cells, IFN-gamma induction assays, DNase I hypersensitive site mapping Blood Medium 8639891
1999 IFN-mediated regulation of the Ly-6E gene in T cells requires multiple regulatory regions including the G region needed for both IFN-alpha/beta and IFN-gamma responses. Multiple transcription factors including Oct-1, Oct-2, and HMGI(Y) bind to regulatory elements in the G region. Inhibition of HMG protein expression by antisense HMGI-C RNA abolishes IFN-alpha/beta and IFN-gamma inducibility of the endogenous Ly-6 gene. Promoter deletion analysis, DNA mobility shift assays (EMSA), antisense RNA inhibition of HMGI-C, IFN-induction assays in EL4 cells Journal of immunology Medium 10395674
1990 PKC (protein kinase C) or a related kinase is required for IFN-mediated Ly-6E induction. PKC inhibitors (H-7, phloretin) block Ly-6E induction by both IFN-gamma and IFN-alpha/beta at mRNA and protein levels. PKC activators (PMA, mezerein) enhance IFN-gamma-mediated but only marginally affect IFN-alpha/beta-mediated Ly-6E induction, indicating IFN-gamma and IFN-alpha/beta utilize overlapping but distinct intracellular pathways. PKC inhibitors and activators applied to YAC T cell lymphoma, Ly-6E mRNA and surface protein measurement Journal of immunology Medium 1692061

Source papers

Stage 0 corpus · 73 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2020 LY6E impairs coronavirus fusion and confers immune control of viral disease. Nature microbiology 189 32704094
2018 LY6E mediates an evolutionarily conserved enhancement of virus infection by targeting a late entry step. Nature communications 112 30190477
1996 RIG-E, a human homolog of the murine Ly-6 family, is induced by retinoic acid during the differentiation of acute promyelocytic leukemia cell. Proceedings of the National Academy of Sciences of the United States of America 101 8650192
2016 Ly6E/K Signaling to TGFβ Promotes Breast Cancer Progression, Immune Escape, and Drug Resistance. Cancer research 93 27197181
2020 LY6E Restricts Entry of Human Coronaviruses, Including Currently Pandemic SARS-CoV-2. Journal of virology 89 32641482
2016 Distinct lymphocyte antigens 6 (Ly6) family members Ly6D, Ly6E, Ly6K and Ly6H drive tumorigenesis and clinical outcome. Oncotarget 77 26862846
1988 The stem cell antigens Sca-1 and Sca-2 subdivide thymic and peripheral T lymphocytes into unique subsets. Journal of immunology (Baltimore, Md. : 1950) 76 2460547
2002 SCA-2 presenting as parkinsonism in an Alberta family: clinical, genetic, and PET findings. Neurology 70 12451209
1997 Expression of the Ly-6E.1 (Sca-1) transgene in adult hematopoietic stem cells and the developing mouse embryo. Development (Cambridge, England) 64 9053329
1998 Spinocerebellar ataxia type 2 (SCA 2) in an infant with extreme CAG repeat expansion. American journal of medical genetics 61 9779806
1994 Mouse stem cell antigen Sca-2 is a member of the Ly-6 family of cell surface proteins. Proceedings of the National Academy of Sciences of the United States of America 54 8202484
1994 Confirmation of the SCA-2 locus as an alternative locus for dominantly inherited spinocerebellar ataxias and refinement of the candidate region. American journal of human genetics 52 8178818
2017 Interferon-inducible LY6E Protein Promotes HIV-1 Infection. The Journal of biological chemistry 49 28130445
2014 IFN-stimulated gene LY6E in monocytes regulates the CD14/TLR4 pathway but inadequately restrains the hyperactivation of monocytes during chronic HIV-1 infection. Journal of immunology (Baltimore, Md. : 1950) 49 25225669
2003 Identification of chicken lymphocyte antigen 6 complex, locus E (LY6E, alias SCA2) as a putative Marek's disease resistance gene via a virus-host protein interaction screen. Cytogenetic and genome research 49 14970721
1995 Modulation of TCR-mediated signaling pathway by thymic shared antigen-1 (TSA-1)/stem cell antigen-2 (Sca-2). Journal of immunology (Baltimore, Md. : 1950) 48 7499840
2016 LY6E: a conductor of malignant tumor growth through modulation of the PTEN/PI3K/Akt/HIF-1 axis. Oncotarget 46 27589564
2019 Emerging Role of LY6E in Virus-Host Interactions. Viruses 43 31684192
1986 Biochemical characterization of the murine activated lymphocyte alloantigen Ly-6E.1 controlled by the Ly-6 locus. Journal of immunology (Baltimore, Md. : 1950) 39 3941270
2018 Production of recombinant TSA-1 and evaluation of its potential for the immuno-therapeutic control of Trypanosoma cruzi infection in mice. Human vaccines & immunotherapeutics 36 30192702
2015 An Antibody-Drug Conjugate Directed against Lymphocyte Antigen 6 Complex, Locus E (LY6E) Provides Robust Tumor Killing in a Wide Range of Solid Tumor Malignancies. Clinical cancer research : an official journal of the American Association for Cancer Research 36 25862760
2018 Trypanosoma cruzi vaccine candidate antigens Tc24 and TSA-1 recall memory immune response associated with HLA-A and -B supertypes in Chagasic chronic patients from Mexico. PLoS neglected tropical diseases 34 29377898
2005 Analysis of SCA-2 and SCA-3 repeats in Parkinsonism: evidence of SCA-2 expansion in a family with autosomal dominant Parkinson's disease. Neuroscience letters 33 15911147
2018 Deletion of the Syncytin A receptor Ly6e impairs syncytiotrophoblast fusion and placental morphogenesis causing embryonic lethality in mice. Scientific reports 29 29500366
2013 Ly6e expression is restricted to syncytiotrophoblast cells of the mouse placenta. Placenta 27 23830620
2017 A Cell Fusion-Based Screening Method Identifies Glycosylphosphatidylinositol-Anchored Protein Ly6e as the Receptor for Mouse Endogenous Retroviral Envelope Syncytin-A. Journal of virology 26 28679758
1989 Biosynthesis of a phosphatidylinositol-glycan-linked membrane protein: signals for posttranslational processing of the Ly-6E antigen. Molecular and cellular biology 26 2796989
2019 CD4-Dependent Modulation of HIV-1 Entry by LY6E. Journal of virology 25 30674630
2022 α5-nAChR associated with Ly6E modulates cell migration via TGF-β1/Smad signaling in non-small cell lung cancer. Carcinogenesis 24 34994389
1994 Multiple glycosylphosphatidylinositol-anchored Ly-6 molecules and transmembrane Ly-6E mediate inhibition of IL-2 production. Journal of immunology (Baltimore, Md. : 1950) 24 8051400
2023 LY6E is a pan-coronavirus restriction factor in the respiratory tract. Nature microbiology 23 37443277
2007 SCA 1, SCA 2 & SCA 3/MJD mutations in ataxia syndromes in southern India. The Indian journal of medical research 23 18160752
1998 Characterization and mapping to human chromosome 8q24.3 of Ly-6-related gene 9804 encoding an apparent homologue of mouse TSA-1. Journal of immunology (Baltimore, Md. : 1950) 23 9551972
2020 A Phase I Study of DLYE5953A, an Anti-LY6E Antibody Covalently Linked to Monomethyl Auristatin E, in Patients with Refractory Solid Tumors. Clinical cancer research : an official journal of the American Association for Cancer Research 20 32694157
1998 Thymic-shared antigen-1 (TSA-1). A lymphostromal cell membrane Ly-6 superfamily molecule with a putative role in cellular adhesion. Developmental immunology 20 9716916
1996 The Ly-6E.1 (Sca-1) gene requires a 3' chromatin-dependent region for high-level gamma-interferon-induced hematopoietic cell expression. Blood 20 8639891
2023 LncRNA LY6E-DT and its encoded metastatic-related protein play oncogenic roles via different pathways and promote breast cancer progression. Cell death and differentiation 18 38114778
1999 Complex regulation of Ly-6E gene transcription in T cells by IFNs. Journal of immunology (Baltimore, Md. : 1950) 17 10395674
2020 LY6E impairs coronavirus fusion and confers immune control of viral disease. bioRxiv : the preprint server for biology 16 32511345
2002 Ectopic expression of TAL-1 protein in Ly-6E.1-htal-1 transgenic mice induces defects in B- and T-lymphoid differentiation. Blood 16 12091340
1993 Cloning of the complete Ly-6E.1 gene and identification of DNase I hypersensitive sites corresponding to expression in hematopoietic cells. Blood 16 8219196
2024 N-acetyltransferase 10 regulates alphavirus replication via N4-acetylcytidine (ac4C) modification of the lymphocyte antigen six family member E (LY6E) mRNA. Journal of virology 15 38169284
1998 Distinct regulatory mechanisms for interferon-alpha/beta (IFN-alpha/beta)- and IFN-gamma-mediated induction of Ly-6E gene in B cells. Blood 15 9746780
1997 The differentiation antigen Ly-6E.1 is expressed in mouse metastatic tumor cell lines. FEBS letters 15 9042962
2022 LY6E protein facilitates adeno-associated virus crossing in a biomimetic chip model of the human blood-brain barrier. Lab on a chip 14 36165190
2021 Preclinical optimization of Ly6E-targeted ADCs for increased durability and efficacy of anti-tumor response. mAbs 14 33382956
1990 Role of protein kinase C in IFN-mediated Ly-6E antigen induction. Journal of immunology (Baltimore, Md. : 1950) 13 1692061
2020 Dendritic Cell-Based Therapy Using LY6E Peptide with a Putative Role Against Colorectal Cancer. ImmunoTargets and therapy 12 32548075
2018 Arsenate-dependent growth is independent of an ArrA mechanism of arsenate respiration in the termite hindgut isolate Citrobacter sp. strain TSA-1. Canadian journal of microbiology 11 30169127
2020 Computational Analysis of the Global Effects of Ly6E in the Immune Response to Coronavirus Infection Using Gene Networks. Genes 9 32708319
2002 Testis-specific antigen (TSA-1) is expressed in murine sperm and its antibodies inhibit fertilization. American journal of reproductive immunology (New York, N.Y. : 1989) 9 11883748
1996 TNFalpha and anti-Fas antibodies regulate Ly-6E.1 expression by tumor cells: a possible link between angiogenesis and Ly-6E.1. Immunology letters 9 9052880
2021 LINC00473 exacerbates osteoarthritis development by promoting chondrocyte apoptosis and proinflammatory cytokine production through the miR-424-5p/LY6E axis. Experimental and therapeutic medicine 8 34539843
2023 Efficient hydroxylation of flavonoids by using whole-cell P450 sca-2 biocatalyst in Escherichia coli. Frontiers in bioengineering and biotechnology 7 36873357
2020 Protein LY6E as a candidate for mediating transport of adeno-associated virus across the human blood-brain barrier. Journal of neurovirology 7 32839948
2025 Induction of LY6E regulates interleukin-1β production, potentially contributing to the immunopathogenesis of systemic lupus erythematosus. Cell communication and signaling : CCS 6 40114200
1991 Multiple cytokine interactions regulate Ly-6E antigen expression: cooperative Ly-6E induction by IFNs, TNF, and IL-1 in a T cell lymphoma and in its induction-deficient variants. Cellular immunology 6 1717166
2025 Immunomodulatory activity of Trypanosoma cruzi recombinant antigen combination TSA-1-C4 and Tc24-C4 induce activation of macrophages and CD8+ T cells. Parasitology research 5 39853538
2024 Ly6E on tumor cells impairs anti-tumor T-cell responses: a novel mechanism of tumor-induced immune exclusion. Cancer immunology, immunotherapy : CII 5 39487896
2023 A LY6E-PHB1-TRIM21 assembly degrades CD14 protein to mitigate LPS-induced inflammatory response. iScience 5 37250795
2024 Exploring Molecular Drivers of PARPi Resistance in BRCA1-Deficient Ovarian Cancer: The Role of LY6E and Immunomodulation. International journal of molecular sciences 4 39408764
2022 Blood RNA Sequencing Indicates Upregulated BATF2 and LY6E and Downregulated ISG15 and MT2A Expression in Children with Autism Spectrum Disorder. International journal of molecular sciences 4 36077244
2025 The NF-κB/LY6E axis promotes oral squamous cell carcinoma stemness by responding to interaction with macrophages. Experimental cell research 3 40582585
2025 Altered LY6E and TRIM6 expression in PBMCs correlated with HBsAg clearance and response to Peg-IFN-α treatment in HBeAg-negative chronic hepatitis B patients. Virology journal 2 40089754
2025 Glycosylphosphatidylinositol biosynthesis functions as a conserved host defense pathway against coronaviruses via regulation of LY6E. PLoS pathogens 2 40901862
2024 Innovative biomarkers TCN2 and LY6E can significantly inhibit respiratory syncytial virus infection. Journal of translational medicine 2 39313785
2023 LY6E protects mice from pathogenic effects of murine coronavirus and SARS-CoV-2. bioRxiv : the preprint server for biology 2 36747632
2025 Nuclear PD-L1 drives IFN-γ-promoted lung metastasis of triple-negative breast cancer via POLR2A-mediated transcriptional activation of LY6E. Breast cancer research : BCR 1 41388312
1991 Modulation of IFN-mediated Ly-6E antigen induction by cAMP in a T cell lymphoma: opposite effects on the responses to IFN-gamma and IFN-alpha/beta. Cellular immunology 1 1846325
2026 Immunotherapy of TSA-1.C4 or in combination with BNZ confers protection against Trypanosoma cruzi infection with a distinct cytokine response. Vaccine 0 41637895
2026 Targeting LY6E Inhibits Neuroblastoma Progression and Suppresses M2 Macrophage Polarization. Human mutation 0 41993132
2026 Computationally guided discovery of Ly6e/LY6E-dependent AAV capsid variants. iScience 0 42028008
2024 Chagasin from Trypanosoma cruzi as a molecular scaffold to express epitopes of TSA-1 as soluble recombinant chimeras. Protein expression and purification 0 38423156

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