Affinage

CD59

CD59 glycoprotein · UniProt P13987

Length
128 aa
Mass
14.2 kDa
Annotated
2026-06-09
100 papers in source corpus 29 papers cited in narrative 29 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

CD59 is a GPI-anchored cell-surface glycoprotein whose primary role is to protect host cells from complement-mediated lysis by restricting assembly of the membrane attack complex (MAC) (PMID:1377690, PMID:11435315). It acts through direct protein-protein contacts, binding specifically to the alpha-chain of C8 and the C9b domain of C9 but not other complement subunits (PMID:1377690); cryo-EM of inhibited C5b8 and C5b9 precursors shows that CD59 engages the pore-forming β-hairpins of C8 to form an intermolecular β-sheet that prevents membrane perforation and deflects cascading C9 β-hairpins to halt polymerization (PMID:36797260). This protective function is physiologically essential: CD59 knockout mice undergo spontaneous intravascular hemolysis from MAC-mediated erythrocyte destruction (PMID:11435315), and a homozygous p.Cys89Tyr mutation that prevents CD59 surface localization causes congenital chronic hemolysis with relapsing demyelinating polyneuropathy in humans (PMID:23149847), with all characterized congenital mutants failing to inhibit MAC formation (PMID:30533526). Complement inhibition requires correct membrane positioning rather than glycosylation, since unglycosylated and even transmembrane-anchored CD59 retain inhibitory activity when appropriately localized (PMID:9176120, PMID:7522635, PMID:9884334). Beyond complement regulation, CD59 serves several signaling and adhesion roles: it is a second ligand for the T-cell receptor CD2, driving adhesion and CD58-dependent, Asn18-glycosylation-dependent costimulation (PMID:1385156, PMID:7521361); it physically associates with the NK natural cytotoxicity receptors NKp46 and NKp30 and enhances cytotoxicity through GPI-anchor-dependent signaling (PMID:14635045, PMID:16493049); and CD59 cross-linking triggers death signaling via APO2L/TRAIL secretion in T cells and Syk-dependent necroptosis in erythrocytes (PMID:10760796, PMID:26018734). A distinct intracellular function is exercised by alternatively spliced non-GPI cytosolic isoforms (IRIS-1/IRIS-2) that bind the exocytotic SNARE proteins VAMP2, Syntaxin-1, and SNAP25 to drive regulated insulin secretion in pancreatic β-cells (PMID:24726385, PMID:35666870). CD59 is also exploited as a receptor by the CD59-dependent cholesterol-dependent cytolysins intermedilysin and vaginolysin, which bind CD59 to coordinate prepore assembly (PMID:27910935, PMID:27499440). Its expression is transcriptionally controlled by p53, REST, and SOX2 (PMID:16489052, PMID:19884909, PMID:28017655).

Mechanistic history

Synthesis pass · year-by-year structured walk · 24 steps
  1. 1992 High

    Established the molecular basis of complement inhibition by defining exactly which MAC components CD59 contacts, moving the field from a phenomenological 'protectin' to a defined molecular interaction.

    Evidence Radiolabeled CD59 binding assays, ligand blotting of C8 subunits, and proteolytic mapping of C9 in vitro

    PMID:1377690

    Open questions at the time
    • Did not resolve the structural mechanism of how binding blocks pore formation
    • Stoichiometry within an assembling MAC not defined
  2. 1992 High

    Identified a complement-independent function of CD59 as a CD2 ligand, revealing CD59 as an adhesion and immune-signaling molecule rather than solely a complement regulator.

    Evidence CHO transfection, antibody-blockable rosette assays, radiolabeled CD59 binding to CD2+ cells, and CD2R epitope induction

    PMID:1385156

    Open questions at the time
    • Did not establish downstream signaling consequences
    • Physiological relevance versus complement role unaddressed
  3. 1992 Medium

    Showed CD59 functions in detergent-resistant GPI-anchored membrane complexes containing CD55 and kinase activity, hinting at organized membrane signaling platforms.

    Evidence Co-immunoprecipitation with anti-CD59/anti-CD55 and kinase activity assay of immunoprecipitates from HPB ALL cells

    PMID:1715364

    Open questions at the time
    • Kinase not identified
    • Complex composition not fully characterized
    • Single Co-IP approach
  4. 1992 Medium

    Demonstrated direct costimulatory activity of CD59 in T-cell activation, distinguishing it from a passive adhesion molecule.

    Evidence Single and double CHO transfectants in rosette and T-cell proliferation assays with submitogenic PHA + IL-1

    PMID:1370512

    Open questions at the time
    • Mechanism of synergy with CD58 unresolved at this stage
    • Single lab
  5. 1994 High

    Defined the molecular requirements for CD59 costimulation, establishing dependence on CD58 co-expression and Asn18 N-glycosylation.

    Evidence CHO transfectants with site-directed Asn18 mutagenesis, proliferation and IL-2 secretion assays with fixed transfectants

    PMID:7521361

    Open questions at the time
    • Did not define the signaling cascade downstream of costimulation
    • Contrast with glycosylation-independent complement function not reconciled mechanistically
  6. 1994 Medium

    Established that the GPI anchor is dispensable for complement inhibition, separating membrane attachment mode from inhibitory function.

    Evidence Retroviral transduction of transmembrane CD59 into GPI-deficient PNH B cells, complement lysis and PI-PLC assays

    PMID:7522635

    Open questions at the time
    • GPI-anchored CD59 could not be expressed on GPI-deficient L cells, limiting direct comparison
    • Spatial positioning requirement not yet defined
  7. 1997 High

    Confirmed N-glycosylation is not required for complement-inhibitory activity, dissociating the glycan requirement seen in costimulation from the complement role.

    Evidence Asn-16 glycosylation-site mutagenesis of rat CD59 expressed in CHO cells with multi-species complement lysis assays

    PMID:9176120

    Open questions at the time
    • Performed in rat CD59; species generalization not formally tested in human
    • Effect on non-complement functions not addressed
  8. 1999 Medium

    Established that effective complement inhibition requires CD59 positioned in close proximity to MAC assembly sites, defining a spatial constraint on its activity.

    Evidence IgG-CD59 chimeric fusion proteins targeted to antigen-positive CHO cells with complement protection assays

    PMID:9884334

    Open questions at the time
    • Quantitative distance/proximity threshold not defined
    • Bystander protection limits not generalized to native tissue
  9. 2001 High

    Provided in vivo proof that CD59 is physiologically required to protect erythrocytes from complement, validating the biochemical model in a whole-organism context.

    Evidence CD59-knockout mice with acidified serum lysis test, reticulocyte counts, plasma/urine hemoglobin, and cobra venom factor challenge

    PMID:11435315

    Open questions at the time
    • Did not address non-erythroid or signaling functions in vivo
    • Compensation by other complement regulators not evaluated
  10. 2003 High

    Identified CD59 as an NK cell co-receptor physically and functionally coupled to natural cytotoxicity receptors, extending its immune signaling role.

    Evidence Co-IP with NKp46/NKp30, anti-CD59 cytotoxicity assays, and CD3ζ phosphorylation analysis

    PMID:14635045

    Open questions at the time
    • Direct versus indirect association with NCRs not resolved
    • Endogenous ligand for this co-receptor function unknown
  11. 2006 High

    Showed CD59-driven NK enhancement requires GPI-anchor-dependent signaling and is glycosylation-independent, mechanistically distinguishing the signaling pathway from membrane raft localization.

    Evidence CD59 anchor variants (GPI, BiMP, transmembrane) in U937 cells, NK cytotoxicity, calcium flux after cross-linking, and lipid raft fractionation

    PMID:16493049

    Open questions at the time
    • Identity of GPI-coupled signaling intermediates not defined
    • Link to NCR association not mechanistically integrated
  12. 2006 Medium

    Identified p53 as a transcriptional regulator of CD59, connecting complement protection to tumor-suppressor and stress signaling.

    Evidence In vitro p53 binding to CD59 promoter elements, siRNA knockdown with CD59 Western blot, and acetylation analysis in HeLa cells

    PMID:16489052

    Open questions at the time
    • Direct in vivo promoter occupancy not shown
    • Physiological context of p53-CD59 axis not established
  13. 2006 Medium

    Showed REST represses neuronal CD59, and that relieving this repression protects neurons from complement, linking CD59 regulation to neural cell vulnerability.

    Evidence REST-derived peptide transfection in neuroblastoma and human neurons with CD59 expression and complement lysis assays

    PMID:19884909

    Open questions at the time
    • Direct REST binding to CD59 regulatory regions not mapped
    • Single lab
  14. 2006 Medium

    Revealed that CD59 cross-linking actively signals cell death via selective APO2L/TRAIL secretion, recasting CD59 as a death-signaling receptor in T cells.

    Evidence Anti-CD59 cross-linking on Jurkat cells with FasL/TRAIL/APO2L blocking antibodies and confirmation in normal T-cell blasts

    PMID:10760796

    Open questions at the time
    • Proximal signaling from CD59 to APO2L secretion not defined
    • Physiological trigger of cross-linking unknown
  15. 2010 Medium

    Demonstrated that CD59-restricted MAC formation protects against vascular pathology, linking complement control to aortic aneurysm and MMP/AP-1/NF-kB signaling.

    Evidence CD59 knockout and human CD59 transgenic mice in angiotensin II aneurysm model with C9, MMP, and AP-1/NF-kB readouts plus in vitro MAC stimulation

    PMID:20212283

    Open questions at the time
    • Cell type driving the protective effect not isolated
    • Whether sublytic MAC versus lysis dominates the phenotype unclear
  16. 2014 High

    Uncovered an unexpected intracellular role for CD59 in regulated insulin exocytosis through SNARE binding, revealing function beyond the cell surface.

    Evidence Co-IP with VAMP2 and Syntaxin-1, siRNA silencing, TIRF imaging, PI-PLC cleavage, and insulin secretion assays in β-cells

    PMID:24726385

    Open questions at the time
    • Molecular form of intracellular CD59 not yet defined at this stage
    • Mechanism of SNARE regulation not resolved
  17. 2015 Medium

    Defined a Syk-dependent receptor signaling pathway by which CD59 engagement drives erythrocyte necroptosis, mechanistically linking CD59 to programmed cell death.

    Evidence CD59 cross-linking and toxin treatment with Syk inhibition, FasL blocking, and phosphorylation analysis of Band 3, RIP1, RIP3

    PMID:26018734

    Open questions at the time
    • Physiological relevance to in vivo hemolysis not established
    • Coupling of CD59 to Syk activation not defined
  18. 2016 High

    Defined the structural mechanism by which CD59-dependent cholesterol-dependent cytolysins exploit CD59, including a proline selectivity switch ensuring CD59 binding precedes cholesterol engagement.

    Evidence Crystal structures of VLY:CD59 and ILY:CD59, SAXS, molecular dynamics, and EM/AFM of prepore intermediates

    PMID:27499440 PMID:27910935

    Open questions at the time
    • Host benefit or consequence of serving as a toxin receptor not addressed
    • How CD59 release during pore maturation is triggered structurally not fully defined
  19. 2016 Medium

    Identified SOX2 as a CD59 transcriptional activator that shields cancer stem cells from complement, connecting CD59 regulation to tumorigenesis and immune evasion.

    Evidence CD59/SOX2 siRNA silencing, complement lysis assays, and xenograft tumorigenesis in nude mice

    PMID:28017655

    Open questions at the time
    • Direct SOX2 binding at the human CD59 locus not fully mapped
    • Cancer-type generality not established
  20. 2018 Medium

    Systematically characterized all known congenital CD59 mutations, showing they all yield nonfunctional protein that fails to inhibit MAC despite varied surface trafficking and antibody recognition.

    Evidence Expression of four mutants with myc-tag and anti-CD59 labeling, glycosylation Western blots, secretion analysis, and complement lysis assays

    PMID:30533526

    Open questions at the time
    • Structural basis for antibody non-recognition of surface-reaching mutants not solved
    • Genotype-phenotype variability not explained
  21. 2018 Medium

    Linked CD59 deficiency to radioresistance via Src kinase signaling and impaired DNA damage repair, indicating CD59 influences intracellular stress responses in cancer.

    Evidence CD59 knockdown/overexpression in ESCC cells with gamma-H2AX, cell cycle, senescence, phospho-Src Y416 analysis, and Src inhibitor treatment

    PMID:30166523

    Open questions at the time
    • Direct molecular link between CD59 and Src activation not defined
    • Surface versus intracellular CD59 contribution not distinguished
  22. 2021 Medium

    Placed CD59 within the LecA-Gb3 lipid raft domain co-opted for P. aeruginosa invasion, implicating CD59-containing membrane domains in host-pathogen entry.

    Evidence LecA pulldown with mass spectrometry and CD59 depletion bacterial invasion assays

    PMID:33555391

    Open questions at the time
    • Whether CD59 is functionally required or a bystander raft constituent not fully resolved
    • Direct CD59-LecA interaction not demonstrated
  23. 2022 High

    Resolved the molecular identity of intracellular insulin-regulating CD59 as alternatively spliced non-GPI cytosolic isoforms (IRIS-1/2) that bind SNAREs and are required for secretion, completing the mechanistic picture of CD59 in β-cell exocytosis.

    Evidence Splice-variant cloning, Co-IP with VAMP2/SNAP25, insulin-granule colocalization, CD59-KO rescue, and CRISPR knockout of mouse intracellular isoforms

    PMID:35666870

    Open questions at the time
    • Precise step in SNARE assembly modulated by IRIS isoforms not defined
    • Relevance to human diabetes not established
  24. 2023 High

    Provided the high-resolution structural mechanism of MAC inhibition, showing CD59 forms an intermolecular beta-sheet with C8 hairpins and deflects C9 hairpins to halt polymerization.

    Evidence Cryo-EM of C5b8:CD59 and C5b9:CD59 with cellular lysis assays and molecular dynamics simulations

    PMID:36797260

    Open questions at the time
    • Stoichiometry of CD59 needed per MAC in vivo not addressed
    • Kinetics of CD59 capture during rapid assembly not resolved

Open questions

Synthesis pass · forward-looking unresolved questions
  • How CD59's distinct activities — surface complement inhibition, GPI-coupled co-receptor signaling, death-pathway triggering, and intracellular SNARE-mediated exocytosis — are coordinated and physiologically prioritized within and across cell types remains unresolved.
  • No unifying model linking GPI-anchored signaling to defined intracellular effectors
  • Regulation of splice-isoform choice between canonical CD59 and IRIS isoforms not characterized
  • Relative in vivo contribution of complement-dependent versus complement-independent functions not quantified

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0098772 molecular function regulator activity 3 GO:0001618 virus receptor activity 2 GO:0060089 molecular transducer activity 2 GO:0098631 cell adhesion mediator activity 2
Localization
GO:0005886 plasma membrane 3 GO:0005829 cytosol 2
Pathway
R-HSA-168256 Immune System 3 R-HSA-162582 Signal Transduction 2 R-HSA-5357801 Programmed Cell Death 2 R-HSA-5653656 Vesicle-mediated transport 2
Partners
C8C9CD2CD58NKP30NKP46STX1AVAMP2
Complex memberships
MAC (C5b-9) inhibitory complexlipid raft / GPI-anchored signaling complex

Evidence

Reading pass · 29 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1992 CD59 binds specifically to the alpha-chain of C8 and to the C9b domain (37-kDa fragment) of C9, but not to C8 beta, C8 gamma, C9a, C5b6, or C7, establishing that CD59 inhibits MAC assembly through direct protein-protein interactions with these specific complement components. Radiolabeled (125I) CD59 binding assays to surface-adsorbed complement proteins, ligand blotting after SDS-PAGE separation of C8 subunits, and thrombin digestion of C9; saturable binding with defined Kd values The Journal of biological chemistry High 1377690
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 into the membrane rather than allowing polymerization, thereby restricting structural transitions of subsequent C9 monomers and indirectly halting MAC polymerization. Cryo-electron microscopy structures of C5b8:CD59 and C5b9:CD59 complexes, combined with cellular complement lysis assays and molecular dynamics simulations Nature communications High 36797260
2001 Targeted gene deletion of CD59 in mice causes spontaneous intravascular hemolysis: CD59-deficient erythrocytes show increased susceptibility to complement in vitro, and mice have elevated reticulocyte counts plus hemoglobin in plasma and urine, demonstrating that CD59 is required in vivo to protect erythrocytes from MAC-mediated lysis. Gene targeting in embryonic stem cells to generate CD59-knockout mice; in vitro acidified serum lysis test; reticulocyte counts; plasma and urine hemoglobin measurements; cobra venom factor challenge Blood High 11435315
1992 CD59 functions as a second ligand for the T cell surface molecule CD2: CHO cells expressing human CD59 form rosettes with human T cells inhibitable by anti-CD59 and anti-CD2 antibodies; radiolabeled CD59 binds specifically to CD2-expressing cells; and CD59 binding to T cells induces expression of CD2R epitopes, indicating a direct CD59–CD2 adhesion interaction. CHO cell transfection with CD59 cDNA; rosette assay with antibody blocking; 125I-labeled CD59 binding to CD2+ transfectants; CD2R epitope induction assay European journal of immunology High 1385156
1992 CD59 is physically associated in a detergent-resistant complex with an 80-kDa glycoprotein, CD55, and glycolipids on HPB ALL cells; the complex also contains protein kinase activity, suggesting CD59 participates in GPI-anchored membrane signaling complexes. Co-immunoprecipitation from detergent lysates with anti-CD59 and anti-CD55 mAbs; SDS-PAGE analysis; protein kinase activity assay of immunoprecipitates Journal of immunology Medium 1715364
1992 CD59 and CD58 exhibit additive/synergistic roles in T cell adhesion and activation: CD59-expressing CHO transfectants alone induce T cell rosettes and sevenfold proliferation enhancement, while double CD58+CD59 transfectants produce >40-fold enhancement—far exceeding the sum of single transfectants—demonstrating direct costimulatory function of CD59. Stable CHO cell transfectants expressing CD59, CD58, or both; rosette assay; T cell proliferation assay with submitogenic PHA + IL-1 Journal of immunology Medium 1370512
1994 CD59 costimulation of T cell activation requires CD58 co-expression and N-glycosylation at Asn18: CD59 enhanced CD58-dependent proliferation and IL-2 secretion, but a glycosylation-deficient CD59 (mutated at Asn18) abolished this costimulatory activity, while CD59 alone without CD58 could not support proliferation. CHO transfectants expressing rCD58, rCD59, or both; site-directed mutagenesis of N-glycosylation site Asn18; T cell proliferation and IL-2 secretion assays with paraformaldehyde-fixed transfectants Journal of immunology High 7521361
2003 CD59 functions as a co-receptor in human NK cell activation: CD59 is physically associated with NKp46 and NKp30 (natural cytotoxicity receptors), and antibody engagement of CD59 enhances NK cytotoxicity in an NKp46-dependent manner, triggering tyrosine phosphorylation of CD3ζ chains associated with NKp46 and NKp30 but not CD16. Co-immunoprecipitation of CD59 with NCRs; NK cytotoxicity assays with anti-CD59 mAb; NKp46 modulation experiments; biochemical phosphorylation analysis of CD3ζ chains European journal of immunology High 14635045
2014 CD59 regulates insulin secretion through intracellular interactions with exocytotic SNARE proteins VAMP2 and Syntaxin-1: most CD59 in pancreatic β-cells is intracellular; silencing intracellular CD59 markedly suppresses regulated exocytosis, while removing extracellular CD59 only moderately stimulates secretion; CD59 co-immunoprecipitates with VAMP2 and Syntaxin-1. Co-immunoprecipitation of CD59 with VAMP2 and Syntaxin-1; siRNA silencing of CD59; TIRF microscopy imaging of exocytosis; PI-PLC cleavage to remove extracellular CD59; insulin secretion assays Cell metabolism High 24726385
2022 Alternative splicing of the CD59 gene produces non-GPI-anchored cytosolic isoforms (IRIS-1 and IRIS-2) in human pancreatic β-cells that interact with SNARE proteins VAMP2 and SNAP25, colocalize with insulin granules, and rescue insulin secretion in CD59-knockout cells; CRISPR/Cas9 knockout of the mouse intracellular isoforms (not canonical CD59B) specifically abrogates insulin secretion. RT-PCR and sequencing of CD59 splice variants; co-immunoprecipitation with VAMP2 and SNAP25; confocal colocalization with insulin granules; CD59-KO cell rescue experiments; CRISPR/Cas9 knockout of mouse isoforms; insulin secretion assays Proceedings of the National Academy of Sciences of the United States of America High 35666870
1997 N-glycosylation of rat CD59 is not required for complement-inhibitory function: a point-mutant lacking the N-glycosylation site at Asn-16 (reducing MW from ~20-28 kDa to ~12 kDa) retains at least as potent complement-inhibitory activity as the wild-type molecule. Site-directed mutagenesis of N-glycosylation site; expression in CHO cells; complement lysis assay with multiple species' sera; antibody blocking confirmation Immunology High 9176120
2006 CD59-mediated NK cell activation and enhanced target cell susceptibility to NK killing requires GPI anchor-dependent signaling: GPI-anchored CD59 (by transfection or membrane incorporation) increases NK cytotoxicity against target cells, whereas CD59 anchored via a bis-myristoylated peptide or a transmembrane domain does not, despite similar lipid raft localization; unglycosylated GPI-anchored CD59 retains this activity, confirming GPI anchor dependence and glycosylation independence. CD59 transfection and membrane incorporation with different anchor types (GPI, BiMP, transmembrane) in U937 cells; NK cytotoxicity assays; calcium flux assays after CD59 cross-linking; lipid raft fractionation Journal of immunology High 16493049
2006 Cross-linking of CD59 on Jurkat T cells induces cell death via preferential secretion of APO2L/TRAIL (not FasL or TRAIL), distinct from TCR-mediated AICD which uses both FasL and TRAIL; this was confirmed in normal human T cell blasts where anti-CD59 cross-linking supernatants were toxic in a manner fully blocked by anti-APO2L antibody. Anti-CD59 antibody cross-linking on Jurkat and J.RT3.T3.5 cells; blocking antibodies against FasL, TRAIL, and anti-APO2L; cytotoxicity assays on supernatants; normal T cell blasts confirmation European journal of immunology Medium 10760796
1993 CD59 expression on endothelial cells is upregulated at the transcriptional level by PKC activators (PMA) and PKA activators (db-cAMP), with functional consequence of increased resistance to complement-mediated lysis; Northern blot showed increases in CD59 mRNA (particularly 1.9, 2.1, and 5.8 kb transcripts). PKC and PKA agonist treatment of EA.hy 926 endothelial cells; flow cytometry of surface CD59; Northern blot analysis; complement lysis assay European journal of immunology Medium 7691609
1993 Enhanced CD59 (MIRL) expression in response to PMA is regulated at the level of transcription and requires de novo protein synthesis: PMA-induced CD59 RNA upregulation was abrogated by both a protein synthesis inhibitor and a transcription inhibitor, consistent with induction of a trans-acting factor that promotes CD59 transcription. PMA stimulation of K562 cells; Northern blot for CD59 RNA; immunoprecipitation and Western blot for CD59 protein; cycloheximide (protein synthesis inhibitor) and actinomycin D (transcription inhibitor) experiments Blood Medium 7687899
2006 CD59 expression is regulated by p53: p53 binds two putative p53-responsive elements in the CD59 gene in vitro; p53 knockdown by siRNA reduces CD59 protein expression sixfold in HeLa cells; acetylation status of p53 modulates CD59 expression in cells exposed to inflammatory cytokines. In vitro p53 binding to CD59 gene p53-responsive elements; siRNA knockdown of p53; Western blot of CD59 protein; acetylation status analysis; camptothecin-induced apoptosis model Cancer research Medium 16489052
2006 CD59 expression in neurons is regulated by the neural-restrictive silencer factor (REST), which represses CD59 transcription; a REST-derived peptide (REST5) containing the nuclear localization domain upregulates CD59 expression fivefold in neurons and protects them from complement-mediated lysis. REST peptide transfection in neuroblastoma cells and human neurons differentiated from neural progenitor cells; CD59 expression measurements; complement lysis assays with human serum or oligodendroglia-conditioned medium The pharmacogenomics journal Medium 19884909
2016 SOX2 transcription factor upregulates CD59 expression in epithelial cancer stem cells to protect them from complement-dependent cytotoxicity; CD59 silencing in cancer stem cells enhanced complement-mediated destruction and suppressed tumorigenesis in xenograft models; SOX2 also regulates mCd59b transcription in murine testis spermatogonial stem cells. CD59 and SOX2 siRNA silencing; sphere-forming cancer stem cell preparation; complement lysis assays; xenograft tumorigenesis in nude mice; SOX2-CD59 transcriptional regulation analysis Stem cell reports Medium 28017655
2016 Intermedilysin (ILY) binds CD59 to coordinate monomer assembly and trigger collapse of an oligomeric prepore: CD59 is required for specific coordination of ILY monomers; movement of ILY Domain 2 relative to Domain 3 forms a late prepore intermediate that releases CD59, while cholesterol mediates transmembrane segment insertion. Biochemical binding assays; electron microscopy; atomic force microscopy of ILY pore formation intermediates Scientific reports High 27910935
2016 Crystal structures of vaginolysin and intermedilysin (CD59-responsive cholesterol-dependent cytolysins) complexed with CD59 show that each toxin binds CD59 at different but overlapping sites; the proline substitution in the CDC undecapeptide consensus motif acts as a selectivity switch ensuring CD59-dependent CDCs bind CD59 before cholesterol. X-ray crystal structures of VLY:CD59 and ILY:CD59 complexes; small-angle X-ray scattering; molecular dynamics simulations; binding studies Structure High 27499440
2015 CD59 receptor signaling drives Syk-dependent erythrocyte necroptosis: binding or crosslinking of CD59 leads to Syk-dependent echinocyte formation with Band 3 phosphorylation and FasL release; FasL-dependent phosphorylation of RIP1, combined with membrane pore formation, triggers RIP3 phosphorylation and necroptosis execution. CD59 antibody crosslinking; human CD59-targeted pore-forming toxin treatment; Syk inhibition; FasL blocking antibody; phosphorylation analysis of Band 3, RIP1, RIP3; cell death assays Cell death & disease Medium 26018734
2010 CD59 protects against abdominal aortic aneurysm development: CD59-deficient mice develop more severe angiotensin II-induced aneurysms with increased C9 deposition, MMP2/9 activity, and phosphorylated AP-1/NF-κB components; transgenic human CD59 overexpression attenuates aneurysm progression; MAC directly induces MMP-2 and MMP-9 gene expression in vitro through AP-1 and NF-κB pathways. CD59 knockout and human CD59 transgenic mice in ApoE-null angiotensin II aneurysm model; C9 deposition measurement; MMP2/9 activity assays; phosphorylation of AP-1/NF-κB components; in vitro MAC stimulation of gene expression Circulation Medium 20212283
2021 CD59 is an integral component of the LecA-Gb3 lipid raft membrane domain in P. aeruginosa invasion: flotillins and CD59 co-purify with the LecA-interacting domain by pulldown and mass spectrometry; depletion of CD59 reduces PAO1 bacterial invasiveness by ~50%. Pulldown and mass spectrometry of LecA-associated membrane domain; CD59 depletion; bacterial invasion assay measuring P. aeruginosa PAO1 uptake Cellular and molecular life sciences Medium 33555391
1994 Transmembrane-anchored recombinant CD59 expressed on GPI-anchoring deficient PNH B cells confers resistance to complement-mediated lysis, demonstrating that GPI anchoring is not strictly required for CD59 complement-inhibitory function; however, GPI-anchored CD59 cannot be expressed on GPI-deficient L cells while transmembrane CD59 can. Retroviral transduction of transmembrane CD59 (CD59-TM) construct into GPI-deficient PNH B cells and mouse L cells; complement lysis assay with human serum; PI-PLC treatment to confirm membrane anchor type; flow cytometry Blood Medium 7522635
1992 CD59 gene has a structure of one 5'-untranslated exon and three coding exons spanning >27 kb, and produces multiple mRNA isoforms (>4) through alternative polyadenylation at distinct sites in the 3' region. Genomic library cloning; Southern blotting; Northern blot with six different 3'-region probes; RACE (rapid amplification of cDNA ends) Journal of molecular biology Medium 1383553
2018 CD59 deficiency promotes radioresistance of esophageal cancer cells through Src kinase activation: CD59 deficiency exacerbates DNA damage, impairs DNA damage repair, induces G2/M arrest and senescence, and reduces Src phosphorylation at Y416 after ionizing radiation; pharmacological Src inhibition sensitizes cells to radiation. CD59 knockdown/overexpression in ESCC cell lines; irradiation; DNA damage assays (γ-H2AX); cell cycle analysis; senescence assay; Western blot for phospho-Src Y416; Src inhibitor saracatinib treatment Cell death & disease Medium 30166523
2012 A homozygous p.Cys89Tyr missense mutation in CD59 causes failure of proper CD59 localization to the cell surface membrane, resulting in congenital chronic hemolysis and relapsing peripheral demyelinating polyneuropathy; mutant protein is present intracellularly but undetectable on the membrane surface by flow cytometry and Western blot. Homozygosity mapping, exome sequencing, Sanger sequencing; flow cytometry for CD59/CD55/CD14 surface expression; Western blot of CD59 protein Blood Medium 23149847
2018 All four known CD59 congenital mutations generate nonfunctional CD59 that fails to inhibit MAC formation; two missense mutants (p.Cys64Tyr and p.Asp24Val) reach the cell surface but are not recognized by known anti-CD59 antibodies; two frameshift mutants remain intracellular; all mutants show normal glycosylation but mutant-specific secretion patterns. Cloning and expression of all four mutants in plasmids; myc-tag immunolabeling; anti-CD59 antibody labeling; Western blot for glycosylation; complement lysis (MAC-dependent cell lysis) assays; secretion analysis Neurology. Genetics Medium 30533526
1999 An antibody–CD59 fusion protein (IgG-CD59) targeted to cell surfaces via antigen binding provides complement protection specifically to antigen-positive cells but not bystander cells; CD59 must be positioned in close proximity to MAC formation sites for effective function, and non-GPI membrane attachment modes affect CD59 activity. Construction and expression of IgG-CD59 chimeric fusion proteins with CD59 at different Ig region positions; binding to dansyl-labeled CHO cells; complement lysis protection assay The Journal of clinical investigation Medium 9884334

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2003 Antigen-presenting cell exosomes are protected from complement-mediated lysis by expression of CD55 and CD59. European journal of immunology 287 12645951
2001 Tumor cell expression of CD59 is associated with resistance to CD20 serotherapy in patients with B-cell malignancies. Journal of immunotherapy (Hagerstown, Md. : 1997) 165 11394505
2001 Targeted deletion of the CD59 gene causes spontaneous intravascular hemolysis and hemoglobinuria. Blood 116 11435315
2012 CD59 deficiency is associated with chronic hemolysis and childhood relapsing immune-mediated polyneuropathy. Blood 114 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 92 23474221
2006 The role of complement regulatory proteins (CD55 and CD59) in the pathogenesis of autoimmune hemocytopenias. Autoimmunity reviews 84 17289551
1992 CD58 and CD59 molecules exhibit potentializing effects in T cell adhesion and activation. Journal of immunology (Baltimore, Md. : 1950) 83 1370512
2005 Analysis of changes in CD20, CD55, and CD59 expression on established rituximab-resistant B-lymphoma cell lines. Leukemia research 76 16289746
1991 Association of the CD59 and CD55 cell surface glycoproteins with other membrane molecules. Journal of immunology (Baltimore, Md. : 1950) 76 1715364
2003 CD59 is physically and functionally associated with natural cytotoxicity receptors and activates human NK cell-mediated cytotoxicity. European journal of immunology 74 14635045
2000 Cytokine-mediated up-regulation of CD55 and CD59 protects human hepatoma cells from complement attack. Clinical and experimental immunology 71 10931136
2022 Silencing EGFR-upregulated expression of CD55 and CD59 activates the complement system and sensitizes lung cancer to checkpoint blockade. Nature cancer 70 36271172
1996 Expression of CD46, CD55, and CD59 on renal tumor cell lines and their role in preventing complement-mediated tumor cell lysis. Laboratory investigation; a journal of technical methods and pathology 69 8667608
1995 Structure of the human urokinase receptor gene and its similarity to CD59 and the Ly-6 family. European journal of biochemistry 69 7531640
2014 The complement inhibitor CD59 regulates insulin secretion by modulating exocytotic events. Cell metabolism 64 24726385
1994 The expression of CD59 in normal human nervous tissue. Immunology 63 7530684
2023 Structural basis for membrane attack complex inhibition by CD59. Nature communications 60 36797260
2000 Identification and functional characterization of a new gene encoding the mouse terminal complement inhibitor CD59. Journal of immunology (Baltimore, Md. : 1950) 59 10946279
1994 Functional and antigenic similarities between a 94-kD protein of Schistosoma mansoni (SCIP-1) and human CD59. The Journal of experimental medicine 58 7513011
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
2004 Characterization of human CD55 and CD59 transgenic pigs and kidney xenotransplantation in the pig-to-baboon combination. Transplantation 56 15167611
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
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
1992 Expression of the DAF (CD55) and CD59 antigens during normal hematopoietic cell differentiation. Journal of leukocyte biology 50 1281489
2018 CD59: a promising target for tumor immunotherapy. Future oncology (London, England) 48 29521526
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
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
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
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
2017 C-reactive protein upregulates the whole blood expression of CD59 - an integrative analysis. PLoS computational biology 40 28922377
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
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
2018 CD59 is a potential biomarker of esophageal squamous cell carcinoma radioresistance by affecting DNA repair. Cell death & disease 37 30166523
1999 CD59-deficient blood cells and PIG-A gene abnormalities in Japanese patients with aplastic anaemia. British journal of haematology 37 10086790
1999 Targeting of functional antibody-CD59 fusion proteins to a cell surface. The Journal of clinical investigation 36 9884334
2010 Expression of CD55 and CD59 on peripheral blood cells from systemic lupus erythematosus (SLE) patients. Cellular immunology 35 20727519
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
2000 Expression of complement regulatory proteins CR1, DAF, MCP and CD59 in haematological malignancies. European journal of haematology 34 10680700
2017 Low expression of complement inhibitory protein CD59 contributes to humoral autoimmunity against astrocytes. Brain, behavior, and immunity 33 28476558
2016 CD59 Regulation by SOX2 Is Required for Epithelial Cancer Stem Cells to Evade Complement Surveillance. Stem cell reports 33 28017655
1994 CD59 costimulation of T cell activation. CD58 dependence and requirement for glycosylation. Journal of immunology (Baltimore, Md. : 1950) 33 7521361
2016 Cre-inducible human CD59 mediates rapid cell ablation after intermedilysin administration. The Journal of clinical investigation 32 27159394
2016 Structural Basis for Receptor Recognition by the Human CD59-Responsive Cholesterol-Dependent Cytolysins. Structure (London, England : 1993) 31 27499440
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
2020 CD59 receptor targeted delivery of miRNA-1284 and cisplatin-loaded liposomes for effective therapeutic efficacy against cervical cancer cells. AMB Express 30 32185543
2005 Effects of CD59 on antitumoral activities of phycocyanin from Spirulina platensis. Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie 30 16271846
1993 Colocalization of the human CD59 gene to 11p13 with the MIC11 cell surface antigen. Genomics 29 7691713
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
1992 CD59: a molecule involved in antigen presentation as well as downregulation of membrane attack complex. Experimental and clinical immunogenetics 28 1379443
2009 CD59 silencing via retrovirus-mediated RNA interference enhanced complement-mediated cell damage in ovary cancer. Cellular & molecular immunology 27 19254481
2006 Cloning of a CD59-like gene in rainbow trout. Expression and phylogenetic analysis of two isoforms. Molecular immunology 27 16876248
2006 Expression of complement restriction factors (CD46, CD55 & CD59) in head and neck squamous cell carcinomas. Journal of oral pathology & medicine : official publication of the International Association of Oral Pathologists and the American Academy of Oral Pathology 27 16968237
1996 Transfected CD59 protects mesangial cells from injury induced by antibody and complement. Kidney international 27 8807596
2018 CRISPR/Cas9 generated human CD46, CD55 and CD59 knockout cell lines as a tool for complement research. Journal of immunological methods 26 29447841
2006 Cell-surface density of complement restriction factors (CD46, CD55, and CD59): oral squamous cell carcinoma versus other solid tumors. Oral surgery, oral medicine, oral pathology, oral radiology, and endodontics 26 17234541
2000 CD59 cross-linking induces secretion of APO2 ligand in overactivated human T cells. European journal of immunology 26 10760796
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
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
2009 Upregulating CD59: a new strategy for protection of neurons from complement-mediated degeneration. The pharmacogenomics journal 25 19884909
2019 Relating GPI-Anchored Ly6 Proteins uPAR and CD59 to Viral Infection. Viruses 24 31739586
2015 CD59 signaling and membrane pores drive Syk-dependent erythrocyte necroptosis. Cell death & disease 24 26018734
2011 Gecko CD59 is implicated in proximodistal identity during tail regeneration. PloS one 24 21464923
2006 p53 regulates cellular resistance to complement lysis through enhanced expression of CD59. Cancer research 24 16489052
2006 Expression of glycosylphosphatidylinositol-anchored CD59 on target cells enhances human NK cell-mediated cytotoxicity. Journal of immunology (Baltimore, Md. : 1950) 24 16493049
2016 Disentangling the roles of cholesterol and CD59 in intermedilysin pore formation. Scientific reports 23 27910935
1999 Decreased expression of protectin (CD59) in gut epithelium in ulcerative colitis and Crohn's disease. Human pathology 23 10667419
2008 Modulation of CD59 expression by restrictive silencer factor-derived peptides in cancer immunotherapy for neuroblastoma. Cancer research 22 18632654
2001 Tumor Cell Expression of CD59 Is Associated With Resistance to CD20 Serotherapy in Patients With B-Cell Malignancies. Journal of immunotherapy : official journal of the Society for Biological Therapy 22 11395643
2014 Rapid degradation of the complement regulator, CD59, by a novel inhibitor. The Journal of biological chemistry 21 24616098
2013 Zebrafish CD59 has both bacterial-binding and inhibiting activities. Developmental and comparative immunology 20 23707788
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
2017 Demyelination, strokes, and eculizumab: Lessons from the congenital CD59 gene mutations. Molecular immunology 19 28622911
2015 Expression of membrane complement regulators, CD46, CD55 and CD59, in mesothelial cells of patients on peritoneal dialysis therapy. Molecular immunology 19 25725314
2000 Role and regulation of pig CD59 and membrane cofactor protein/CD46 expressed on pig aortic endothelial cells. Transplantation 19 10972227
2012 Absence of CD59 exacerbates systemic autoimmunity in MRL/lpr mice. Journal of immunology (Baltimore, Md. : 1950) 18 23109726
1993 Enhanced expression of the complement regulatory protein, membrane inhibitor of reactive lysis (CD59), is regulated at the level of transcription. Blood 18 7687899
2018 Molecular pathogenesis of human CD59 deficiency. Neurology. Genetics 17 30533526
2001 Detection of CD55- and/or CD59-deficient red cell populations in patients with lymphoproliferative syndromes. The hematology journal : the official journal of the European Haematology Association 17 11920231
2001 Expression of 17-1A antigen and complement resistance factors CD55 and CD59 on liver metastasis in colorectal cancer. Journal of gastrointestinal surgery : official journal of the Society for Surgery of the Alimentary Tract 17 12086907
2015 Paroxysmal nocturnal hemoglobinuria (PNH) and primary p.Cys89Tyr mutation in CD59: Differences and similarities. Molecular immunology 16 25818314
2011 Expression of complement regulatory proteins CD55, CD59, CD35, and CD46 in rheumatoid arthritis. Revista brasileira de reumatologia 16 21953001

Missed literature

Know a paper Affinage missed for CD59? Flag it for the maintainers and the community.

No submissions yet.