Affinage

CD59

CD59 glycoprotein · UniProt P13987

Length
128 aa
Mass
14.2 kDa
Annotated
2026-04-28
100 papers in source corpus 27 papers cited in narrative 27 extracted findings

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

CD59 is a GPI-anchored complement regulatory glycoprotein that protects host cells from membrane attack complex (MAC)-mediated lysis and additionally functions in T cell co-stimulation, insulin exocytosis, and pathogen exploitation of lipid rafts. Cryo-EM structures show that CD59 binds the pore-forming β-hairpins of C8α via a hydrophobic pocket centered on Tyr61, forming an intermolecular β-sheet that prevents membrane perforation and deflects incoming C9 monomers to halt MAC polymerization (PMID:36797260, PMID:1377690, PMID:9075580). Beyond complement regulation, alternatively spliced non-GPI-anchored intracellular isoforms (IRIS-1/IRIS-2) interact with SNARE proteins VAMP2 and SNAP25 to promote insulin granule exocytosis in pancreatic β-cells, with IRIS-1 expression reduced in type 2 diabetic islets (PMID:35666870, PMID:24726385). Homozygous loss-of-function mutations in CD59 (e.g., p.Cys89Tyr) cause hereditary CD59 deficiency manifesting as chronic hemolysis and demyelinating polyneuropathy (PMID:23149847).

Mechanistic history

Synthesis pass · year-by-year structured walk · 16 steps
  1. 1991 Medium

    Establishing that CD59 exists in membrane signaling complexes: before this study it was unclear whether the small GPI-anchored protein participated in multiprotein assemblies; co-immunoprecipitation revealed CD59 associates with CD55, an 80-kDa glycoprotein, and a protein kinase, indicating it resides in organized membrane signaling domains.

    Evidence Co-immunoprecipitation from detergent lysates with kinase activity assay on human cells

    PMID:1715364

    Open questions at the time
    • Identity of the 80-kDa co-precipitating protein unknown
    • No reciprocal pull-down or independent confirmation
    • Kinase identity not determined
  2. 1992 High

    Defining the molecular targets of CD59 within the MAC: it was unknown which complement components CD59 engaged; binding assays demonstrated direct protein–protein interaction with C8α and the C9b domain of C9 (but not C5b6, C7, or C8β), and showed binding requires a conformational change exposed upon surface adsorption.

    Evidence Radiolabeled (¹²⁵I) CD59 binding to purified complement proteins, ligand blotting, thrombin digestion mapping

    PMID:1377690

    Open questions at the time
    • Structural basis of the conformational change not resolved
    • Stoichiometry of CD59:C8/C9 interaction unknown
  3. 1992 High

    Identifying CD59 as a second ligand for CD2 on T cells: beyond complement regulation, CD59 was shown to bind CD2 directly and induce CD2R epitope expression, establishing a complement-independent role in T cell adhesion and activation.

    Evidence Rosette formation with CD59-transfected CHO cells, competitive binding with ¹²⁵I-labeled CD59, antibody blocking

    PMID:1385156

    Open questions at the time
    • Downstream signaling pathway from CD59-CD2 interaction not mapped
    • Physiological relevance in vivo not established
  4. 1993 Medium

    Demonstrating transcriptional regulation of CD59: CD59 expression was known to vary across cell types but how it was regulated was unclear; PMA, calcium ionophore, and cAMP were shown to upregulate CD59 mRNA and protein on endothelial and K562 cells, with PMA acting through a newly synthesized trans-acting factor.

    Evidence Northern blot, flow cytometry, complement lysis assay, transcription/translation inhibitor studies in endothelial and K562 cells

    PMID:7687899 PMID:7691609

    Open questions at the time
    • Identity of the PMA-induced trans-acting factor unknown
    • Promoter elements mediating the response not mapped
  5. 1996 High

    Mapping the functional active site of CD59: systematic mutagenesis identified Tyr61 as critical for complement inhibition, defined required disulfide bridges for surface expression, and showed the Cys64-Cys69 disulfide constrains rather than enables function, establishing the structural determinants of activity.

    Evidence Site-directed mutagenesis of cysteines and Tyr61, cell-surface expression and complement lysis assays

    PMID:9075580

    Open questions at the time
    • No high-resolution structure at this time to confirm spatial arrangement
    • Contribution of other residues in the hydrophobic pocket not tested
  6. 1999 Medium

    Demonstrating that a transmembrane-anchored CD59 can functionally replace the GPI-anchored form: this showed the GPI anchor is dispensable for complement protection per se, relevant to potential gene therapy for PNH.

    Evidence Retroviral transduction of transmembrane CD59 into GPI-anchor-deficient PNH B cells, complement lysis assay

    PMID:7522635

    Open questions at the time
    • In vivo efficacy of transmembrane CD59 not tested
    • Whether transmembrane form participates in signaling not addressed
  7. 2001 High

    Validating CD59 as essential for erythrocyte protection in vivo: CD59 knockout mice exhibited spontaneous intravascular hemolysis and hemoglobinuria, confirming the non-redundant physiological requirement for MAC regulation on red blood cells.

    Evidence Gene-targeted CD59 knockout mice, acidified serum lysis, plasma/urine hemoglobin, reticulocyte counts

    PMID:11435315

    Open questions at the time
    • Single-gene knockout may not model human PNH (which also lacks CD55)
    • Neurological phenotype not examined in mice
  8. 2006 High

    Pinpointing the C9 recognition epitope and shared binding pocket: a 6-residue C9 sequence (365–371) was identified as the primary CD59-binding domain, and both C8α and C9 were found to engage an overlapping hydrophobic pocket on CD59, explaining how one small protein blocks two sequential MAC components.

    Evidence Peptide screens, synthetic peptide binding/lysis assays, computational docking

    PMID:16844690

    Open questions at the time
    • No co-crystal structure to confirm docking model
    • Whether CD59 can simultaneously contact C8 and C9 not resolved
  9. 2006 Medium

    Establishing CD59 as an enhancer of NK cell cytotoxicity in a GPI-anchor-dependent manner: GPI-anchored but not transmembrane or BiMP-anchored CD59 enhanced NK killing and triggered Ca²⁺ flux, revealing anchor-type specificity for signaling functions distinct from complement regulation.

    Evidence NK cytotoxicity assays, Ca²⁺ flux measurements, GPI vs. transmembrane CD59 variants on transfected cells

    PMID:16493049

    Open questions at the time
    • NK receptor partner for CD59 not identified
    • Downstream signaling pathway in NK cells not mapped
  10. 2010 High

    Linking CD59 to vascular disease pathogenesis: CD59 deficiency accelerated angiotensin II–induced aortic aneurysm in ApoE-null mice while human CD59 transgenic expression was protective, with MAC shown to induce MMP-2/MMP-9 via AP-1 and NF-κB, establishing a mechanistic complement–MMP axis in aneurysm progression.

    Evidence CD59 KO and transgenic mice, Ang II infusion, MMP activity assays, pathway Western blots, in vitro MAC treatment

    PMID:20212283

    Open questions at the time
    • Whether CD59 modulates aneurysm independently of MAC not tested
    • Applicability to human aortic disease not confirmed
  11. 2012 Medium

    Demonstrating that inherited CD59 deficiency causes a Mendelian disease: the p.Cys89Tyr mutation abolished surface localization of CD59, causing chronic hemolysis and demyelinating polyneuropathy and establishing CD59 deficiency as a discrete clinical entity.

    Evidence Homozygosity mapping, exome sequencing, flow cytometry, Western blot in a consanguineous family

    PMID:23149847

    Open questions at the time
    • Single family; limited genotype–phenotype correlation
    • Mechanism of demyelination not elucidated
  12. 2014 High

    Uncovering a complement-independent role for CD59 in insulin secretion: intracellular CD59 was shown to be required for regulated exocytosis in β-cells and to physically interact with SNARE proteins VAMP2 and Syntaxin-1, establishing CD59 as a dual-function protein.

    Evidence TIRF imaging, co-immunoprecipitation, siRNA knockdown, PI-PLC cleavage in INS-1 and human β-cells

    PMID:24726385

    Open questions at the time
    • Structural basis of CD59–SNARE interaction unknown
    • Whether complement-regulatory and exocytotic functions use distinct protein surfaces not determined
  13. 2014 Medium

    Mapping CD59 signaling through Lck to the TCR/CD3 pathway: CD59-triggered Ca²⁺ signals in T cells required Lck and LAT, and physically tethering Lck to CD3ζ abolished CD59 signaling while preserving TCR responses, placing CD59 upstream of Lck in a lipid-raft-initiated signaling cascade.

    Evidence Single-cell Ca²⁺ imaging, siRNA knockdown of Lck/LAT, Lck-CD3ζ chimera in Jurkat cells

    PMID:24454946

    Open questions at the time
    • Mechanism by which GPI-anchored CD59 activates cytoplasmic Lck not resolved
    • Not confirmed in primary T cells
  14. 2016 High

    Revealing how bacterial cholesterol-dependent cytolysins (CDCs) exploit CD59: crystal structures of vaginolysin and intermedilysin bound to CD59 showed overlapping but distinct binding sites and identified a proline selectivity switch in the CDC undecapeptide that ensures CD59 engagement before cholesterol binding, defining CD59 as a pathogen receptor.

    Evidence X-ray crystallography, SAXS, MD simulations, binding assays for ILY and VLY–CD59 complexes

    PMID:27499440 PMID:27910935

    Open questions at the time
    • Whether the CD59 site used by CDCs overlaps with the complement-inhibitory site not fully resolved
    • In vivo relevance to Gardnerella/Streptococcus infection not tested
  15. 2022 High

    Identifying alternatively spliced intracellular CD59 isoforms as dedicated exocytotic regulators: IRIS-1 and IRIS-2 lack the GPI signal, localize to the cytosol and insulin granules, interact with VAMP2 and SNAP25, and rescue insulin secretion in CD59-KO cells; IRIS-1 is reduced in T2D islets, linking CD59 splicing to diabetes pathogenesis.

    Evidence Isoform cloning, CRISPR KO and rescue, Co-IP, TIRF imaging, isoform-specific antibodies in human islets

    PMID:35666870

    Open questions at the time
    • Structural basis of IRIS isoform–SNARE interaction not determined
    • Whether IRIS isoforms exist in non-β-cell secretory cells unknown
  16. 2023 High

    Resolving the atomic mechanism of MAC inhibition by CD59: cryo-EM structures of CD59-bound C5b8 and C5b9 showed CD59 forms an intermolecular β-sheet with C8 β-hairpins to block perforation and simultaneously deflects C9 β-hairpins to prevent MAC polymerization, unifying decades of biochemical data into a single structural framework.

    Evidence Cryo-EM structures at near-atomic resolution, complement lysis assays, MD simulations

    PMID:36797260

    Open questions at the time
    • Dynamic on-rate kinetics of CD59 engagement with assembling MAC in live membranes not measured
    • Whether CD59 can disengage and recycle after blocking one MAC not addressed

Open questions

Synthesis pass · forward-looking unresolved questions
  • Key unresolved questions include how GPI-anchored CD59 transduces signals to cytoplasmic kinases (Lck, Src) without an intracellular domain, the structural basis of IRIS isoform–SNARE complex formation, and whether complement-regulatory and signaling/exocytotic functions of CD59 use overlapping or distinct protein surfaces.
  • No structure of CD59–SNARE complex
  • Trans-membrane signaling mechanism for GPI-anchored CD59 unknown
  • Overlap between CDC-binding and complement-binding surfaces on CD59 not fully resolved

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0098772 molecular function regulator activity 7
Localization
GO:0005886 plasma membrane 6 GO:0031410 cytoplasmic vesicle 2 GO:0005829 cytosol 1
Pathway
R-HSA-168256 Immune System 6 R-HSA-162582 Signal Transduction 3 R-HSA-5653656 Vesicle-mediated transport 2
Partners
C8AC9CD2LCKSNAP25STX1AVAMP2

Evidence

Reading pass · 27 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2023 Cryo-EM structures of inhibited MAC precursors C5b8 and C5b9 reveal that CD59 binds the pore-forming β-hairpins of C8 to form an intermolecular β-sheet that prevents membrane perforation; while bound to C8, CD59 deflects cascading C9 β-hairpins, rerouting their trajectory into the membrane, which restricts structural transitions of subsequent C9 monomers and halts MAC polymerization. Cryo-electron microscopy, cellular lysis assays, molecular dynamics simulations Nature Communications High 36797260
1992 CD59 binds specifically to the α-chain of C8 and to the C9b domain (residues within the 37-kDa thrombin fragment) of C9, but not to C5b6, C7, or C8β; binding occurs via protein-protein interaction (not via the GPI phospholipid moiety) and is detected only when C8/C9 are surface-adsorbed, suggesting a conformational change exposes the CD59 binding site. Radiolabeled (125I) CD59 binding assay with density gradient analysis, surface adsorption assay, ligand blotting after SDS-PAGE separation of C8 subunits, alpha-thrombin digestion of C9 The Journal of Biological Chemistry High 1377690
2006 A 6-residue sequence of human C9 spanning residues 365-371 constitutes the primary CD59 recognition domain; both C8α and C9 bind to a similar or overlapping hydrophobic pocket on CD59; docking models indicate C9 residues 365-371 interact with the hydrophobic pocket on CD59 previously identified by mutagenesis. Peptide screens, binding assays with synthetic peptides, functional complement lysis assays, computer modeling and docking studies The Journal of Biological Chemistry High 16844690
1996 Site-directed mutagenesis of CD59 reveals: disulfide bridges maintaining the three finger-like loops (Cys3-Cys26, Cys19-Cys39, Cys45-Cys63) are required for cell surface expression; the Cys64-Cys69 disulfide in the small loop is not required for expression and its removal increases function; the functional site involves residues around Tyr61 (Tyr61→Gly abrogates function); the Arg53 region is the major epitope for most anti-CD59 monoclonal antibodies. Site-directed mutagenesis of disulfide bridges and specific residues, cell surface expression assays, complement lysis functional assays, antibody binding assays Blood Cells, Molecules & Diseases High 9075580
2014 CD59 in pancreatic β-cells functions as a regulator of insulin secretion: extracellular CD59 disrupts membrane rafts and moderately stimulates insulin secretion when removed, while intracellular CD59 is required for regulated exocytosis; CD59 physically interacts with exocytotic SNARE proteins VAMP2 and Syntaxin-1. TIRF imaging, co-immunoprecipitation, CD59 silencing (siRNA), PI-PLC cleavage of surface CD59 Cell Metabolism High 24726385
2022 Alternative splicing of CD59 in human pancreatic β-cells produces non-GPI-anchored intracellular isoforms (IRIS-1 and IRIS-2) with unique C-terminal domains; these isoforms localize to the cytosol, colocalize with insulin granules, interact with SNARE proteins VAMP2 and SNAP25, and rescue insulin secretion in CD59-knockout cells. IRIS-1 expression is reduced by glucotoxicity and in human T2D islets. Alternative splicing characterization, Co-immunoprecipitation with VAMP2/SNAP25, TIRF imaging, CRISPR/Cas9 knockout, rescue experiments, isoform-specific antibodies Proceedings of the National Academy of Sciences of the United States of America High 35666870
2001 CD59-deficient mice generated by gene targeting show spontaneous intravascular hemolysis and hemoglobinuria, with increased erythrocyte complement susceptibility in vitro and elevated reticulocyte counts and hemoglobin in plasma/urine, demonstrating that CD59 is required to protect erythrocytes from spontaneous MAC-mediated lysis in vivo. Gene targeting in ES cells, acidified serum lysis test, in vitro complement lysis assay, plasma/urine hemoglobin measurement, reticulocyte counts Blood High 11435315
1992 CD59 acts as a second ligand for the CD2 molecule on T cells: CHO cells transfected with human CD59 form rosettes with human T cells inhibitable by anti-CD59 and anti-CD2 antibodies; radiolabeled CD59 binds specifically to CD2-expressing CHO cells and this binding is blocked by unlabeled CD59 and anti-CD2 antibody; binding of CD59 to resting T cells induces CD2R epitope expression. Rosette formation assay with CHO transfectants, competitive binding assay with 125I-labeled CD59, antibody blocking studies European Journal of Immunology High 1385156
1994 CD59 co-stimulates CD58-dependent T cell activation: CD59-expressing CHO cells enhance CD58-dependent T cell proliferation and IL-2 secretion in the presence of suboptimal PHA or anti-CD2 antibodies; this co-stimulation requires N-glycosylation of CD59 at Asn18 and is dependent on co-expression of CD58. T cell proliferation assays and IL-2 secretion assays with CD59/CD58 CHO transfectants, paraformaldehyde fixation, N-glycosylation mutant analysis, antibody blocking Journal of Immunology Medium 7521361
2014 CD59-mediated signaling in Jurkat T cells is transmitted to the TCR/CD3 pathway through Lck: siRNA knockdown of Lck or LAT abolishes CD59-triggered Ca2+ signaling; physically linking Lck to CD3ζ completely abolishes CD59-triggered Ca2+ signaling while direct TCR/CD3 stimulation remains functional, placing Lck downstream of CD59 but upstream of TCR/CD3. Single-cell Ca2+ imaging, siRNA knockdown, TCR/CD3-deficient and overexpressing cell lines, co-patterning and FRAP experiments, flow cytometry PloS One Medium 24454946
1991 Anti-CD59 and anti-CD55 monoclonal antibodies co-immunoprecipitate an 80-kDa glycoprotein from detergent lysates along with their respective antigens, and the CD59 immunoprecipitate contains a protein kinase activity, indicating that CD59 exists in noncovalent membrane complexes with this 80-kDa protein, CD55, glycolipids, and an associated kinase. Immunoprecipitation from detergent lysates, co-precipitation of associated proteins, protein kinase activity assay Journal of Immunology Medium 1715364
2006 Expression of GPI-anchored CD59 on human target cells enhances NK cell-mediated cytotoxicity; this requires the GPI anchor for signaling (BiMP- and transmembrane-anchored CD59 do not enhance NK killing even when in lipid rafts); GPI-anchored CD59 mediates activation events (Ca2+ flux) upon crosslinking, whereas non-GPI forms do not; glycosylation is not required. NK cytotoxicity assays, CD59 transfection and membrane incorporation, GPI anchor variants, Ca2+ flux assays, antibody blocking Journal of Immunology Medium 16493049
2006 p53 regulates CD59 expression: two p53-responsive elements in the CD59 gene bind p53 in vitro; siRNA knockdown of p53 reduces CD59 protein expression ~6-fold in HeLa cells; acetylation status of p53 modulates CD59 expression in response to inflammatory cytokines. p53 binding assay (in vitro), siRNA knockdown of p53, Western blotting, complement lysis assay, cytokine treatment Cancer Research Medium 16489052
1993 CD59 expression on endothelial cells (EA.hy 926) is up-regulated ~3-fold by protein kinase C inducers PMA and calcium ionophore A23187, and by the PKA inducer dibutyryl-cAMP; this up-regulation occurs at the mRNA level and results in increased resistance to complement-mediated cell lysis. Flow cytometry, Northern blot analysis, complement-mediated lysis assay European Journal of Immunology Medium 7691609
1993 Enhanced CD59 (MIRL) expression induced by PMA in K562 cells is regulated at the transcriptional level; PMA-induced up-regulation of MIRL RNA and protein is abrogated by inhibitors of protein synthesis and transcription, consistent with PMA inducing a trans-acting protein that enhances MIRL gene transcription. Northern blot analysis, immunoprecipitation of metabolically labeled proteins, Western blot, inhibitors of transcription and protein synthesis Blood Medium 7687899
1997 Glycosylation at Asn-16 of rat CD59 is not required for complement-inhibitory function: a glycosylation mutant lacking N-linked carbohydrate (reduced MW from ~20-28 kDa to ~12 kDa) retains full complement-inhibitory activity against all complement sources tested. Site-directed mutagenesis of N-glycosylation site, SDS-PAGE, CHO cell expression, complement lysis assay with multiple complement sources Immunology Medium 9176120
1996 Overexpression of transfected CD59 in glomerular mesangial cells protects against both lytic and sublytic C5b-9 attack: CD59-transfected cells show marked resistance to complement lysis reversible by anti-CD59 antibody, and overexpressed CD59 suppresses superoxide production induced by sublytic C5b-9. FLAG-tagged CD59 expression vector, stable transfection, immunocytochemistry, Western blotting, complement-mediated lysis assay, superoxide production measurement Kidney International Medium 8807596
2005 Glycation of CD59 on erythrocytes from hyperglycaemic (poorly controlled type 1 diabetes) individuals impairs its complement-inhibitory function in vivo: despite normal surface expression of CD59 by antibody staining, erythrocytes from hyperglycaemic subjects were more susceptible to complement lysis, and this susceptibility was entirely attributable to loss of functional CD59. Flow cytometry (CD59 surface expression), complement lysis assay, comparison of hyperglycaemic vs. normoglycaemic cohort Immunology Medium 15667573
1999 A recombinant transmembrane form of CD59 (CD59-TM) expressed on GPI-anchor-deficient PNH B cells restores complement protection, demonstrating that the GPI anchor is not absolutely required for CD59 function, but alternative membrane attachment can support activity. Retroviral transduction, cell surface expression, PI-PLC cleavage assay (confirms lack of GPI), complement-mediated lysis assay Blood Medium 7522635
2019 Pancreatic cancer-educated macrophages (TAMs) upregulate CD59 on pancreatic cancer cells via the IL-6R/STAT3 signaling pathway, thereby protecting cancer cells from complement-dependent cytotoxicity; STAT3 inhibition abolishes macrophage-induced CD59 upregulation. Co-culture system (THP-1 macrophages + pancreatic cancer cells), RT-PCR, Western blot, immunofluorescence, CDC assay, RNA sequencing, STAT3 inhibitors, siRNA knockdown, antibody neutralization Cell Death & Disease Medium 31685825
2018 CD59 deficiency in esophageal squamous cell carcinoma cells reduces Src kinase phosphorylation (Y416), impairs DNA damage repair, exacerbates DNA damage after ionizing radiation, and causes G2/M arrest and cellular senescence; a Src inhibitor (saracatinib) phenocopies CD59 deficiency in radiosensitization. Lentiviral shRNA knockdown and overexpression, phospho-Src Western blot, γH2AX assay, cell cycle analysis, MTT proliferation assay, Src inhibitor treatment Cell Death & Disease Medium 30166523
2010 CD59 deficiency accelerates angiotensin II-induced abdominal aortic aneurysm in ApoE-null mice, while transgenic overexpression of human CD59 attenuates it; MAC directly induces MMP-2 and MMP-9 gene expression in vitro through AP-1 and NF-κB signaling pathways, defining the mechanistic link between MAC and aneurysm progression. CD59 knockout and transgenic mouse models, angiotensin II infusion model, MMP activity assays, phospho-c-Jun/c-Fos/IKK/p65 Western blots, in vitro MAC treatment with AP-1 and NF-κB pathway analysis Circulation High 20212283
2021 CD59, as an integral component of the LecA-interacting Gb3-enriched membrane domain along with flotillins, facilitates Pseudomonas aeruginosa invasion; depletion of CD59 reduces invasiveness of P. aeruginosa PAO1 by ~50%. Pull-down and mass spectrometry, flow cytometry, siRNA depletion of CD59 and flotillins, bacterial invasion assay Cellular and Molecular Life Sciences Medium 33555391
2016 Crystal structures of vaginolysin and intermedilysin complexed to CD59 reveal that CD59-responsive CDCs bind CD59 at different though overlapping sites; the CDC consensus undecapeptide proline (replacing the conserved tryptophan) acts as a selectivity switch ensuring CD59-dependent CDCs bind their protein receptor before cholesterol. X-ray crystallography, small-angle X-ray scattering, molecular dynamics simulations, binding studies Structure High 27499440
2016 Intermedilysin (ILY) requires CD59 for specific coordination of monomers and to trigger collapse of an oligomeric prepore; Domain 2 movement relative to Domain 3 of ILY is essential for forming a late prepore intermediate that releases CD59, while cholesterol's role is limited to insertion of transmembrane segments. Biochemical assays, electron microscopy, atomic force microscopy, domain movement analysis Scientific Reports High 27910935
2022 EGFR/Wnt signaling induces β-catenin-mediated expression of lncRNA LINC00973, which sponges miR-150 (targeting CD59) and miR-216b (targeting CD55), resulting in CD59 upregulation that suppresses the complement system and blocks cytokine secretion required for CD8+ T cell activation in lung cancer. miRNA sponge mechanism characterization, LINC00973 promoter mutation, anti-CD55/CD59 antibody treatment, complement activation assays, CD8+ T cell activation assays, tumor growth experiments, EGFR/Wnt pathway inhibition Nature Cancer Medium 36271172
2012 A homozygous missense mutation p.Cys89Tyr in CD59 causes loss of surface membrane localization: the mutated protein is present intracellularly in reduced amounts but is undetectable at the cell membrane by flow cytometry and Western blot, leading to chronic hemolysis and demyelinating polyneuropathy. Homozygosity mapping, exome sequencing, Sanger sequencing, flow cytometry for surface CD59 expression, Western blot Blood Medium 23149847

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
1997 Transgenic pigs expressing human CD59 and decay-accelerating factor produce an intrinsic barrier to complement-mediated damage. Transplantation 260 9000677
1993 Membrane defence against complement lysis: the structure and biological properties of CD59. Immunologic research 142 7507156
2001 Targeted deletion of the CD59 gene causes spontaneous intravascular hemolysis and hemoglobinuria. Blood 114 11435315
2012 CD59 deficiency is associated with chronic hemolysis and childhood relapsing immune-mediated polyneuropathy. Blood 113 23149847
2006 Alternative roles for CD59. Molecular immunology 110 16884774
1992 The human complement regulatory protein CD59 binds to the alpha-chain of C8 and to the "b"domain of C9. The Journal of biological chemistry 105 1377690
2000 Deficiency of complement defense protein CD59 may contribute to neurodegeneration in Alzheimer's disease. The Journal of neuroscience : the official journal of the Society for Neuroscience 104 11027207
1992 CD59 molecule: a second ligand for CD2 in T cell adhesion. European journal of immunology 98 1385156
2013 Lipoplex mediated silencing of membrane regulators (CD46, CD55 and CD59) enhances complement-dependent anti-tumor activity of trastuzumab and pertuzumab. Molecular oncology 91 23474221
2006 The role of complement regulatory proteins (CD55 and CD59) in the pathogenesis of autoimmune hemocytopenias. Autoimmunity reviews 84 17289551
2006 Defining the CD59-C9 binding interaction. The Journal of biological chemistry 83 16844690
1996 Complement in acute and chronic arthritides: assessment of C3c, C9, and protectin (CD59) in synovial membrane. Annals of the rheumatic diseases 76 9014582
1991 Association of the CD59 and CD55 cell surface glycoproteins with other membrane molecules. Journal of immunology (Baltimore, Md. : 1950) 76 1715364
1997 Molecular cloning, chromosomal localization, expression, and functional characterization of the mouse analogue of human CD59. Journal of immunology (Baltimore, Md. : 1950) 72 9029105
2000 Cytokine-mediated up-regulation of CD55 and CD59 protects human hepatoma cells from complement attack. Clinical and experimental immunology 70 10931136
2002 Crry, but not CD59 and DAF, is indispensable for murine erythrocyte protection in vivo from spontaneous complement attack. Blood 68 11986227
1998 The complement regulatory proteins CD46 and CD59, but not CD55, are highly expressed by glandular epithelium of human breast and colorectal tumour tissues. APMIS : acta pathologica, microbiologica, et immunologica Scandinavica 68 9808413
2014 The complement inhibitor CD59 regulates insulin secretion by modulating exocytotic events. Cell metabolism 64 24726385
1994 Molecular cloning of the rat analogue of human CD59: structural comparison with human CD59 and identification of a putative active site. The Biochemical journal 63 7528012
2022 Silencing EGFR-upregulated expression of CD55 and CD59 activates the complement system and sensitizes lung cancer to checkpoint blockade. Nature cancer 62 36271172
1994 The expression of CD59 in normal human nervous tissue. Immunology 62 7530684
2000 Identification and functional characterization of a new gene encoding the mouse terminal complement inhibitor CD59. Journal of immunology (Baltimore, Md. : 1950) 59 10946279
1997 Expression and function of the complement membrane attack complex inhibitor protectin (CD59) in human prostate cancer. International journal of cancer 57 9185710
2014 The complement receptors CD46, CD55 and CD59 are regulated by the tumour microenvironment of head and neck cancer to facilitate escape of complement attack. European journal of cancer (Oxford, England : 1990) 56 24915776
2005 Transgenic pigs expressing human CD59, in combination with human membrane cofactor protein and human decay-accelerating factor. Xenotransplantation 56 15693845
2023 Structural basis for membrane attack complex inhibition by CD59. Nature communications 55 36797260
2017 CD55 and CD59 expression protects HER2-overexpressing breast cancer cells from trastuzumab-induced complement-dependent cytotoxicity. Oncology letters 54 28928834
2010 Complement regulator CD59 protects against angiotensin II-induced abdominal aortic aneurysms in mice. Circulation 54 20212283
2004 Characterization of human CD55 and CD59 transgenic pigs and kidney xenotransplantation in the pig-to-baboon combination. Transplantation 54 15167611
2012 Altered expression of CD46 and CD59 on leukocytes in neovascular age-related macular degeneration. American journal of ophthalmology 51 22541656
1994 Expression and function of CD59 on colonic adenocarcinoma cells. European journal of immunology 50 7517877
1994 Expression and function of the complement membrane attack complex inhibitor protectin (CD59) on human breast cancer cells. Laboratory investigation; a journal of technical methods and pathology 49 7528832
1991 The complement-inhibiting protein, protectin (CD59 antigen), is present and functionally active on glomerular epithelial cells. Clinical and experimental immunology 49 1704296
1992 Isolation and characterization of the complement-inhibiting protein CD59 antigen from platelet membranes. The Biochemical journal 48 1372164
1999 Complement regulators C1 inhibitor and CD59 do not significantly inhibit complement activation in Alzheimer disease. Brain research 46 10375708
2005 Transfer of functional prostasomal CD59 of metastatic prostatic cancer cell origin protects cells against complement attack. The Prostate 44 15389819
1998 Structure, distribution, and functional role of protectin (CD59) in complement-susceptibility and in immunotherapy of human malignancies (Review). International journal of oncology 44 9664126
2016 Therapy with eculizumab for patients with CD59 p.Cys89Tyr mutation. Annals of neurology 43 27568864
1996 Structure-function relationships of the complement regulatory protein, CD59. Blood cells, molecules & diseases 42 9075580
1995 Enhanced expression of decay accelerating factor and CD59/homologous restriction factor 20 on the colonic epithelium of ulcerative colitis. Laboratory investigation; a journal of technical methods and pathology 42 7538183
1995 Complement regulation in the rat glomerulus: Crry and CD59 regulate complement in glomerular mesangial and endothelial cells. Kidney international 42 7564108
2014 Glycation of the complement regulatory protein CD59 is a novel biomarker for glucose handling in humans. The Journal of clinical endocrinology and metabolism 41 24628556
2006 Diminished expression of complement regulatory proteins (CD55 and CD59) in lymphocytes from systemic lupus erythematosus patients with lymphopenia. Lupus 41 17080916
2003 Deficiency of red cell bound CD55 and CD59 in patients with systemic lupus erythematosus. Immunology letters 41 12880676
1992 Gene structure of human CD59 and demonstration that discrete mRNAs are generated by alternative polyadenylation. Journal of molecular biology 41 1383553
1992 Expression of the complement regulatory proteins CD21, CD55 and CD59 on Burkitt lymphoma lines: their role in sensitivity to human serum-mediated lysis. European journal of immunology 40 1378022
2017 Overexpression of Human CD55 and CD59 or Treatment with Human CD55 Protects against Renal Ischemia-Reperfusion Injury in Mice. Journal of immunology (Baltimore, Md. : 1950) 39 28500075
2014 Systematic immunohistochemical analysis of the expression of CD46, CD55, and CD59 in colon cancer. Archives of pathology & laboratory medicine 39 24978917
2019 Pancreatic cancer-educated macrophages protect cancer cells from complement-dependent cytotoxicity by up-regulation of CD59. Cell death & disease 38 31685825
2017 C-reactive protein upregulates the whole blood expression of CD59 - an integrative analysis. PLoS computational biology 38 28922377
2004 Analysis of the level of mRNA expression of the membrane regulators of complement, CD59, CD55 and CD46, in breast cancer. International journal of cancer 38 14712499
1999 CD59-deficient blood cells and PIG-A gene abnormalities in Japanese patients with aplastic anaemia. British journal of haematology 37 10086790
2018 CD59 is a potential biomarker of esophageal squamous cell carcinoma radioresistance by affecting DNA repair. Cell death & disease 36 30166523
1999 Targeting of functional antibody-CD59 fusion proteins to a cell surface. The Journal of clinical investigation 36 9884334
1993 Regulation of CD59 expression on the human endothelial cell line EA.hy 926. European journal of immunology 35 7691609
2015 Early-onset chronic axonal neuropathy, strokes, and hemolysis: inherited CD59 deficiency. Neurology 34 25716358
2010 Expression of CD55 and CD59 on peripheral blood cells from systemic lupus erythematosus (SLE) patients. Cellular immunology 34 20727519
2000 Expression of complement regulatory proteins CR1, DAF, MCP and CD59 in haematological malignancies. European journal of haematology 34 10680700
1994 CD59 costimulation of T cell activation. CD58 dependence and requirement for glycosylation. Journal of immunology (Baltimore, Md. : 1950) 33 7521361
2018 Complement-Mediated Activation of the NLRP3 Inflammasome and Its Inhibition by AAV-Mediated Delivery of CD59 in a Model of Uveitis. Molecular therapy : the journal of the American Society of Gene Therapy 31 29678656
2017 Low expression of complement inhibitory protein CD59 contributes to humoral autoimmunity against astrocytes. Brain, behavior, and immunity 31 28476558
2016 Cre-inducible human CD59 mediates rapid cell ablation after intermedilysin administration. The Journal of clinical investigation 31 27159394
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2013 CD59 is overexpressed in human lung cancer and regulates apoptosis of human lung cancer cells. International journal of oncology 31 23835643
1993 Expression of the glycosylphosphatidylinositol-linked complement-inhibiting protein CD59 antigen in insect cells using a baculovirus vector. The Biochemical journal 31 7694573
2013 Shiga toxin 2 reduces complement inhibitor CD59 expression on human renal tubular epithelial and glomerular endothelial cells. Infection and immunity 30 23690395
2001 Protection of xenogeneic cells from human complement-mediated lysis by the expression of human DAF, CD59 and MCP. FEMS immunology and medical microbiology 30 11720816
1990 Isolation and expression of the full-length cDNA encoding CD59 antigen of human lymphocytes. DNA and cell biology 30 1692709
2005 Effects of CD59 on antitumoral activities of phycocyanin from Spirulina platensis. Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie 29 16271846
1993 Colocalization of the human CD59 gene to 11p13 with the MIC11 cell surface antigen. Genomics 29 7691713
2013 Use of complement regulators, CD35, CD46, CD55, and CD59, on leukocytes as markers for diagnosis of viral and bacterial infections. Human immunology 28 23376460
2003 Computerized video time-lapse (CVTL) analysis of the fate of giant cells produced by X-irradiating EJ30 human bladder carcinoma cells. Radiation research 28 12751952
2009 CD59 silencing via retrovirus-mediated RNA interference enhanced complement-mediated cell damage in ovary cancer. Cellular & molecular immunology 27 19254481
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1997 Expression of rat CD59: functional analysis confirms lack of species selectivity and reveals that glycosylation is not required for function. Immunology 26 9176120
2022 Alternative splicing encodes functional intracellular CD59 isoforms that mediate insulin secretion and are down-regulated in diabetic islets. Proceedings of the National Academy of Sciences of the United States of America 25 35666870
2021 The Gb3-enriched CD59/flotillin plasma membrane domain regulates host cell invasion by Pseudomonas aeruginosa. Cellular and molecular life sciences : CMLS 25 33555391
2014 Lck mediates signal transmission from CD59 to the TCR/CD3 pathway in Jurkat T cells. PloS one 25 24454946
2014 Xenoantibody response to porcine islet cell transplantation using GTKO, CD55, CD59, and fucosyltransferase multiple transgenic donors. Xenotransplantation 25 24645827
2013 On the three-finger protein domain fold and CD59-like proteins in Schistosoma mansoni. PLoS neglected tropical diseases 25 24205416
2011 The effects of CD59 gene as a target gene on breast cancer cells. Cellular immunology 25 22000275
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2006 Expression of glycosylphosphatidylinositol-anchored CD59 on target cells enhances human NK cell-mediated cytotoxicity. Journal of immunology (Baltimore, Md. : 1950) 24 16493049
1999 Decreased expression of protectin (CD59) in gut epithelium in ulcerative colitis and Crohn's disease. Human pathology 23 10667419
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2008 Reduction of CD55 and/or CD59 in red blood cells of patients with HIV infection. Medical science monitor : international medical journal of experimental and clinical research 20 18443552
2002 Computerized video time-lapse (CVTL) analysis of cell death kinetics in human bladder carcinoma cells (EJ30) X-irradiated in different phases of the cell cycle. Radiation research 20 12452769
1994 Expression of recombinant transmembrane CD59 in paroxysmal nocturnal hemoglobinuria B cells confers resistance to human complement. Blood 20 7522635
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1995 Down-regulation of CD59 (protectin) expression on human colorectal adenocarcinoma cell lines by levamisole. Scandinavian journal of immunology 19 7481554
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2015 Sequestration of host-CD59 as potential immune evasion strategy of Trichomonas vaginalis. Acta tropica 18 25976413
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