Affinage

CD55

Complement decay-accelerating factor · UniProt P08174

Length
381 aa
Mass
41.4 kDa
Annotated
2026-06-09
100 papers in source corpus 25 papers cited in narrative 26 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 7/7 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

CD55 (DAF) is a GPI-anchored cell-surface glycoprotein whose core function is regulation of the complement cascade, accelerating decay of C3/C5 convertases to protect host cells from complement-mediated attack, an activity localized to its third short consensus repeat (SCR3) (PMID:7511675, PMID:10417349). This protective coat operates not only on cells but also on antigen-presenting-cell exosomes and, in a phospholipase-C-resistant ECM-deposited form on collagen fibers, on synovial tissue, shielding these compartments from C3b deposition and lysis (PMID:12645951, PMID:25596646). Biallelic loss-of-function mutations in CD55 cause CHAPLE syndrome, a human disease of unchecked complement activation on T lymphocytes with C5a generation that is reversed by genetic reconstitution or complement-inhibitory antibody (PMID:28657829). Beyond complement, CD55 transduces intracellular signals despite lacking a transmembrane domain by associating with plasma-membrane tyrosine kinases and a 43-kDa signal-transducing partner, driving tyrosine phosphorylation cascades (PMID:7511675, PMID:1715364, PMID:9620603); in cancer this manifests as complement-independent, lipid-raft-dependent signaling through ROR2/JNK to sustain cancer stem cell self-renewal and through LCK to confer chemoresistance (PMID:28838952). CD55 also serves as a cellular receptor for Enterovirus 70 and Coxsackievirus B3 (via SCR2/SCR3) and is specifically required for Plasmodium falciparum erythrocyte internalization at the moving junction (PMID:8764022, PMID:9601501, PMID:34028351), and acts as the ligand for the adhesion GPCR CD97, an interaction that drives macrophage-mediated arthritis pathology (PMID:10211878, PMID:20131275). CD55 expression and complement-inhibitory efficacy are tightly regulated: transcriptionally by HIF-1α (repressive) and HIF-2α (inductive) under hypoxia and by an EGFR/Wnt/β-catenin–LINC00973 axis, and post-translationally by ST3GAL1-mediated O-sialylation that controls its tumor immune-evasion capacity (PMID:27494303, PMID:27043658, PMID:36271172). In vivo, CD55 restrains adaptive T cell responses in a complement-dependent manner (PMID:15710649).

Mechanistic history

Synthesis pass · year-by-year structured walk · 24 steps
  1. 1994 High

    Established the foundational function of CD55 as a complement regulator and mapped the activity to a defined structural module, answering where in the protein complement inhibition resides.

    Evidence Functional review synthesizing molecular cloning and SCR domain analysis localizing activity to SCR3

    PMID:7511675

    Open questions at the time
    • Atomic-level mechanism of convertase decay acceleration not resolved here
    • Relative contributions of SCR2 vs SCR3 to different ligand interactions not delineated
  2. 1991 Medium

    Addressed how a GPI-anchored protein lacking a cytoplasmic tail could signal, by showing CD55 forms noncovalent membrane complexes with CD59 and an 80-kDa glycoprotein carrying protein kinase activity.

    Evidence Co-immunoprecipitation from HPB ALL detergent lysates with kinase activity assay

    PMID:1715364

    Open questions at the time
    • Identity of the 80-kDa glycoprotein and kinase not defined
    • Single cell line, single lab
  3. 1998 Medium

    Refined the signaling model by identifying a specific 43-kDa DAF-associated transducer whose cross-linking elicits a defined tyrosine phosphorylation cascade.

    Evidence Affinity purification, reciprocal co-immunoprecipitation, and tyrosine phosphorylation assay in PBMCs

    PMID:9620603

    Open questions at the time
    • Molecular identity of the 43-kDa protein unestablished
    • Downstream physiologic consequence of the phosphorylation events unclear
  4. 1996 High

    Demonstrated CD55 is a bona fide viral receptor by reconstituting EV70 binding and replication in heterologous murine cells, opening a non-complement role for the protein.

    Evidence Anti-DAF antibody blocking, heterologous expression in NIH 3T3, radiolabeled virus binding

    PMID:8764022

    Open questions at the time
    • Whether CD55 alone suffices for entry vs requires co-receptors not addressed
    • Binding domain not mapped in this study
  5. 1998 High

    Extended viral receptor use to CVB3 and mapped the binding determinant to SCR2/SCR3, linking the receptor surface to specific structural repeats.

    Evidence Domain-specific antibody blocking, PI-PLC GPI removal, flow cytometry, competitive binding

    PMID:9601501

    Open questions at the time
    • Overlap between virus-binding and complement-regulatory surfaces not fully separated
    • Internalization mechanism not defined here
  6. 1999 High

    Confirmed by gain-of-function reconstitution that CD55, in both GPI and transmembrane isoforms, is sufficient to inhibit complement and protect cells from lysis.

    Evidence Cloning and stable CHO expression with C3b deposition, cell lysis, and hemolytic assays

    PMID:10417349

    Open questions at the time
    • Functional differences between TM and GPI isoforms in vivo not resolved
    • Mouse-human isoform divergence may limit translation
  7. 1999 Medium

    Identified CD55 as the ligand for the seven-transmembrane receptor CD97 and placed this pair in synovial tissue, suggesting a complement-independent adhesion/inflammation role.

    Evidence Immunohistochemistry of synovium and ELISA for soluble CD97

    PMID:10211878

    Open questions at the time
    • Direct functional consequence of CD55-CD97 binding not tested here
    • Binding affinity and stoichiometry not measured
  8. 2003 High

    Showed CD55's protective function extends beyond cells to APC-derived exosomes, broadening the substrate range of complement regulation.

    Evidence Flow cytometry of exosome surface proteins with antibody blocking, C3b deposition and lysis assays

    PMID:12645951

    Open questions at the time
    • In vivo relevance of exosomal CD55 protection not established
    • Mechanism of CD55 sorting onto exosomes unknown
  9. 2005 High

    Established a physiologic immunoregulatory role by showing CD55 restrains adaptive T cell cytokine responses in a complement-dependent manner.

    Evidence Daf1-/- mice with immunization, cytokine restimulation assays, and EAE model with complement disabling

    PMID:15710649

    Open questions at the time
    • Cellular target (T cell intrinsic vs APC) of complement effect not fully separated
    • Human relevance inferred from mouse
  10. 2006 Medium

    Revealed a complement-independent immunopathogenic role, showing CD55 is required for the CD1d/Vγ4+ T cell pathway driving CVB3 myocarditis.

    Evidence DAF-/- infection model with CD1d analysis and T cell subset depletions

    PMID:16817758

    Open questions at the time
    • Molecular link between CD55 and CD1d induction unknown
    • Single lab
  11. 2002 Medium

    Defined how soluble, functionally active CD55 is generated in tissue by showing VEGF induces ECM CD55 and MMP-7 specifically releases it intact.

    Evidence VEGF stimulation of HUVEC, ECM quantification, complement assay, protease release experiments

    PMID:12445304

    Open questions at the time
    • In vivo contribution of MMP-7-released CD55 to tumor complement evasion not shown
    • Single lab
  12. 2010 High

    Demonstrated genetically that the CD55-CD97 axis drives arthritis pathology independent of complement, validating the receptor-ligand interaction functionally.

    Evidence CD55-/- and CD97-/- mice in collagen-induced and K/BxN serum-transfer arthritis models

    PMID:20131275

    Open questions at the time
    • Downstream macrophage signaling from CD97 engagement not detailed
    • Relative weight of adhesion vs complement roles not quantified
  13. 2015 High

    Showed FLS-produced CD55 is deposited on synovial ECM collagen in a PI-PLC-resistant form that protects tissue from immune-complex-driven complement attack.

    Evidence Confocal co-localization, in situ hybridization, PLC resistance assay, K/BxN arthritis in CD55/Fcgr2b double-deficient mice

    PMID:25596646

    Open questions at the time
    • Molecular mechanism anchoring CD55 to collagen unknown
    • Whether ECM CD55 also engages CD97 not addressed
  14. 2017 High

    Defined CD55 as a human disease gene, establishing CHAPLE syndrome as a complement dysregulation disorder caused by CD55 loss and reversible by complement inhibition.

    Evidence Whole-exome sequencing, patient T lymphocyte functional assays, genetic reconstitution and antibody rescue

    PMID:28657829

    Open questions at the time
    • Mechanism of CD55's costimulatory function distinct from complement decay not resolved
    • Genotype-phenotype variability not detailed
  15. 2017 High

    Uncovered a complement-independent, lipid-raft-dependent signaling output of CD55 that bifurcates into ROR2/JNK-driven stemness and LCK-driven chemoresistance in cancer.

    Evidence Lipid raft disruption, ROR2/JNK and LCK pathway inhibition, knockdown with pluripotency and DNA-repair gene readouts

    PMID:28838952

    Open questions at the time
    • How CD55 physically activates ROR2 and LCK at the raft is unknown
    • Generality across tumor types beyond endometrioid not established
  16. 2017 Medium

    Placed CD55 downstream of an oncogenic driver, showing HPV-E6 enriches a tumourigenic CD55+ cell population that requires CD55 for its aggressive phenotype.

    Evidence CRISPR/Cas9 CD55 knockout, ectopic E6 expression, sphere/tumourigenicity/radioresistance assays

    PMID:28944962

    Open questions at the time
    • Mechanism by which E6 enriches CD55+ cells unknown
    • Single lab
  17. 2016 High

    Showed transcriptional control of CD55 by hypoxia factors, with HIF-1α repressing CD55 in airway epithelium to permit local complement activation.

    Evidence Bidirectional HIF-1α manipulation in vitro and in vivo murine hypoxia with complement readouts

    PMID:27494303

    Open questions at the time
    • Direct vs indirect promoter regulation by HIF-1α not dissected
    • Tissue specificity of repression vs induction unexplained
  18. 2016 Medium

    Demonstrated HIF-2α drives CD55 expression in neuroblastoma and that CD55 contributes specifically to invasion and colony growth rather than stemness, separating CD55's roles from the HIF-2α stemness program.

    Evidence HIF-2α gain-of-function and functional comparison of CD55-positive vs negative subpopulations

    PMID:27043658

    Open questions at the time
    • Apparent opposite-direction HIF regulation vs airway epithelium unreconciled
    • Single lab
  19. 2016 Medium

    Showed pathogens exploit CD55 for complement evasion, with HCV inducing a secreted CD55 splice isoform that inhibits C3 convertase systemically.

    Evidence HCV replicon system, RT-PCR splice detection, C3 convertase and cytolysis assays with antibody blocking

    PMID:27357152

    Open questions at the time
    • Cellular source of patient serum sCD55 not pinpointed
    • Single lab
  20. 2016 Medium

    Showed enveloped viruses physically incorporate functional CD55 into virions to resist complement neutralization, a host-protein-hijacking evasion mechanism.

    Evidence Virion protein analysis and complement neutralization comparing CD55-incorporating vs non-incorporating PIV5

    PMID:27505156

    Open questions at the time
    • Mechanism of selective CD55 vs CD46 incorporation unknown
    • Single lab
  21. 2020 High

    Established that O-linked sialylation by ST3GAL1 is required for CD55's complement-inhibitory immune-evasion function, defining a post-translational control point.

    Evidence ST3GAL1 knockdown, mass spectrometry of CD55 glycans, C3 deposition, lysis, and ADCC assays

    PMID:33177111

    Open questions at the time
    • Structural basis for how sialic acid affects convertase decay unknown
    • Generality beyond breast cancer not tested
  22. 2021 High

    Pinpointed the precise step of malaria invasion requiring CD55, showing it acts after rhoptry discharge in moving junction stability rather than in attachment.

    Evidence CRISPR-Cas9 erythrocyte CD55 ablation, antibody inhibition, live cell imaging, deformability/echinocytosis controls

    PMID:34028351

    Open questions at the time
    • Direct parasite ligand for CD55 at the junction not identified
    • Molecular basis of junction stabilization unresolved
  23. 2022 High

    Defined an oncogenic non-coding RNA circuit that upregulates CD55 to suppress complement and CD8+ T cells, and showed therapeutic synergy of CD55 blockade with checkpoint inhibition.

    Evidence EGFR/Wnt/β-catenin manipulation, LINC00973 promoter mutation, miRNA sponge validation, complement and T cell assays, anti-PD-1 combination in vivo

    PMID:36271172

    Open questions at the time
    • Relative contribution of CD55 vs CD59 to the immune suppression not separated
    • Clinical translatability of combination therapy untested
  24. 2019 Medium

    Linked an ERK-dependent stimulus to CD55 induction and complement inactivation, with bee venom restoring CD55 and ameliorating an inflammatory disease model.

    Evidence Expression and ERK phosphorylation assays in THP-1, complement assays, AD mouse model

    PMID:31027358

    Open questions at the time
    • Direct transcriptional effector downstream of ERK not identified
    • Single lab

Open questions

Synthesis pass · forward-looking unresolved questions
  • The molecular identities of the CD55-associated kinases/transducers (80-kDa and 43-kDa partners) and the structural basis by which raft localization couples CD55 to ROR2/JNK and LCK signaling remain unresolved.
  • 80-kDa and 43-kDa associated proteins remain molecularly unidentified
  • No structural model linking CD55 ectodomain engagement to intracellular kinase activation
  • Mechanism of CD55-CD97 signal transduction into macrophages undefined

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0060089 molecular transducer activity 4 GO:0001618 virus receptor activity 3 GO:0098772 molecular function regulator activity 3 GO:0048018 receptor ligand activity 2
Localization
GO:0005886 plasma membrane 3 GO:0031012 extracellular matrix 2
Pathway
R-HSA-168256 Immune System 5 R-HSA-162582 Signal Transduction 3 R-HSA-1643685 Disease 3
Partners
CD59CD97

Evidence

Reading pass · 26 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1994 CD55 (DAF) functions as a complement regulator by inhibiting C3/C5 convertase formation, acting as a species-restricting factor at the level of C3/C5 activation. The third short consensus repeat (SCR3) of DAF is responsible for its complement regulatory activity and signaling. Functional review synthesizing biochemical and molecular cloning data; SCR domain analysis The Journal of laboratory and clinical medicine High 7511675
1994 CD55 is a GPI-anchored protein associated with tyrosine kinases on the inner leaflet of the plasma membrane, enabling signal transduction despite lacking a transmembrane domain. Biochemical association studies; GPI anchor characterization The Journal of laboratory and clinical medicine Medium 7511675
1991 CD55 co-immunoprecipitates with CD59 and a common 80-kDa glycoprotein from detergent lysates, forming noncovalent membrane complexes. These CD55/CD59/80-kDa complexes contain protein kinase activity, linking GPI-anchored CD55 to intracellular signaling. Co-immunoprecipitation from HPB ALL cell line detergent lysates; identification of protein kinase activity in immune complexes Journal of immunology Medium 1715364
1996 CD55 (DAF) is the HeLa cell receptor for Enterovirus 70 (EV70). Anti-DAF monoclonal antibodies inhibited EV70 binding to HeLa cells; stable expression of human DAF in murine NIH 3T3 cells conferred EV70 binding and supported virus replication. Monoclonal antibody blocking assay; heterologous expression of human DAF in NIH 3T3 cells; radiolabeled virus binding assay; immunoprecipitation Journal of virology High 8764022
1998 Cardiovirulent Group B Coxsackievirus 3 (CVB3) uses CD55 (DAF) as an attachment receptor. Anti-DAF monoclonal antibodies directed against SCR2 and SCR3 domains most effectively blocked virus binding and infection. Virus binding was reduced by phosphatidylinositol phospholipase C treatment that removes GPI-anchored DAF. Virus binding and internalization were associated with DAF down-regulation at the cell surface. Monoclonal antibody blocking assay; phospholipase C treatment to deplete GPI-anchored DAF; flow cytometry; competitive binding assays Virology High 9601501
1998 CD55 associates with a specific 43-kDa DAF-associated protein (identified by mAb 2E12-G7) that acts as a signal transducer. Cross-linking of DAF via its associated 43-kDa protein induced tyrosine phosphorylation of proteins of 45, 72, 78 and ~100 kDa in peripheral blood mononuclear cells. This 43-kDa antigen was present in CD55 but not CD59 immunoprecipitates, indicating specific association. Affinity purification of DAF-associated proteins; monoclonal antibody generation; co-immunoprecipitation; surface biotinylation and immunoblotting; tyrosine phosphorylation assay with [gamma-32P]ATP International immunology Medium 9620603
1999 Mouse DAF (CD55) exists in multiple isoforms generated by alternative splicing, including GPI-anchored and transmembrane forms encoded by separate genes (Daf-GPI and Daf-TM). Stable expression of either TM or GPI-anchored mouse DAF in CHO cells reduced C3b deposition and protected cells from complement-mediated lysis in a cell-lysis assay. Soluble recombinant mouse DAF inhibited complement in a haemolytic assay. Molecular cloning; stable transfection of CHO cells; C3b deposition assay; cell lysis assay; haemolytic assay with soluble recombinant DAF The Biochemical journal High 10417349
1999 CD55 is a specific cellular ligand for the seven-transmembrane receptor CD97, and this receptor-ligand pair is expressed on fibroblast-like synoviocytes (FLS) and macrophages respectively in synovial tissue, suggesting a role in mediating FLS-macrophage interactions and maintaining synovial architecture. Immunohistochemical analysis of synovial biopsy specimens; ELISA for soluble CD97 in synovial fluid Arthritis and rheumatism Medium 10211878
2003 Exosomes derived from antigen-presenting cells express GPI-anchored CD55 and CD59 but not the transmembrane protein CD46. Antibody blockade of CD55 in the presence of sensitizing antibody and human serum resulted in increased C3b deposition and significantly increased exosome lysis, demonstrating that CD55 on exosomes functionally protects them from complement-mediated lysis. Flow cytometry of exosome surface proteins; antibody blocking experiments; C3b deposition assay; lysis assay European journal of immunology High 12645951
2005 CD55 (DAF) suppresses adaptive T cell immune responses in vivo. Daf1-/- mice showed significantly enhanced T cell responses to immunization, characterized by hypersecretion of IFN-γ and IL-2 and down-regulation of IL-10. This was complement-dependent: disabling complement in Daf1-/- mice normalized T cell cytokine secretion. CD55 deficiency also exacerbated EAE disease severity, which was also complement-dependent. Daf1 knockout mouse model; active immunization with antigen; in vitro lymphocyte restimulation cytokine assays; EAE model with complement inhibition The Journal of experimental medicine High 15710649
2009 In nonpolarized HeLa cells, DAF-binding CVB3 entry requires dynamin and lipid rafts but not caveolin, clathrin, or endosomal acidification. Unlike in polarized Caco-2 cells, CVB3 entered HeLa cells with CAR (not DAF-mediated entry). Tyrosine kinase inhibition blocked an early infection event but did not prevent virus entry, indicating DAF-mediated tyrosine kinase signaling is not required for entry into nonpolarized cells. Dominant-negative proteins; siRNA knockdown of endocytic pathway components; pharmacologic inhibitors; immunofluorescence microscopy Journal of virology Medium 19710132
2010 Deletion of CD55 ameliorates arthritis in collagen-induced and K/BxN serum-transfer mouse models, demonstrating that CD55 interaction with CD97 on infiltrating macrophages plays a pathogenic role in RA beyond its complement-inhibitory function. Similarly, CD97-/- mice had reduced arthritis, consistent with the CD55/CD97 axis driving disease. CD55-/- and CD97-/- mouse models; collagen-induced arthritis; K/BxN serum transfer arthritis model; clinical and immunohistochemical evaluation Arthritis and rheumatism High 20131275
2015 CD55 produced by fibroblast-like synoviocytes (FLS) is deposited on collagen type I and III reticular fibers in the synovial extracellular matrix; this ECM-associated CD55 is resistant to phospholipase C cleavage and co-localizes with complement C3. CD55 deficiency on a FcγRIIB-null background exaggerated K/BxN-induced arthritis, indicating that ECM-deposited CD55 protects synovial tissue from immune complex-mediated complement attack. Confocal microscopy co-localization; in situ hybridization; flow cytometry; phospholipase C treatment; K/BxN serum transfer arthritis model in CD55/Fcgr2b double-deficient mice; 3D FLS micromass culture Arthritis research & therapy High 25596646
2017 Biallelic loss-of-function mutations in CD55 cause loss of CD55 protein expression, leading to increased complement activation on T lymphocytes with surface deposition of complement and generation of soluble C5a, defective CD55-mediated costimulatory function, and defective cytokine modulation. Genetic reconstitution of CD55 or treatment with a complement-inhibitory antibody reversed abnormal complement activation (CHAPLE syndrome). Whole-exome sequencing; functional assays on patients' T lymphocytes (complement deposition, C5a generation); exogenous induction of CD55 expression for genetic reconstitution; complement-inhibitory antibody treatment The New England journal of medicine High 28657829
2017 In endometrioid cancer, CD55 functions in a complement-independent manner requiring lipid raft localization. CD55 regulates cancer stem cell self-renewal and core pluripotency genes via ROR2/JNK signaling, and in parallel regulates cisplatin resistance via lymphocyte-specific protein tyrosine kinase (LCK) signaling, which induces DNA repair genes. These represent a bifurcating signaling axis downstream of CD55. Comparative CSC vs non-CSC analysis; lipid raft disruption; ROR2/JNK pathway inhibition; LCK inhibitor (saracatinib) treatment; gene expression analysis of pluripotency and DNA repair genes; loss-of-function knockdown The Journal of experimental medicine High 28838952
2016 Hepatitis C virus (HCV) infection induces expression of a secreted isoform of CD55 (sCD55) generated by alternative splicing. Conditioned medium from HCV-infected hepatocytes and serum from chronically HCV-infected patients inhibited C3 convertase activity and complement-dependent cytolysis; CD55-blocking antibody inhibited this effect, implicating sCD55 in impairment of complement function. HCV infection/replicon system; RT-PCR for sCD55 splice variant; C3 convertase inhibition assay; complement-dependent cytolysis assay of sheep erythrocytes; antibody blocking Journal of immunology Medium 27357152
2016 Parainfluenza virus 5 (PIV5) incorporates functional CD55 (and CD46) into virions during assembly. CD55-containing PIV5 virions were highly resistant to complement-mediated neutralization; CD46-containing PIV5 was not. PIV5 infection upregulated cell surface CD55 expression (further enhanced by TNF-α), and virus derived from higher CD55-expressing cells was more complement-resistant in vitro. Virion protein analysis; complement-mediated neutralization assay comparing CD55-incorporating vs non-incorporating virions; flow cytometry of infected cell surface CD55 Virology Medium 27505156
2017 HPV E6 protein expression dramatically enriches the CD55+ subpopulation in cervical cancer cells. The CD55+ subpopulation shows enhanced sphere-forming ability, tumourigenicity, cell migration, and radioresistance. CRISPR/Cas9 knockout of CD55 in HPV-E6-overexpressing cells abolished tumourigenic effects of the E6 protein, placing CD55 downstream of E6 in a pathway promoting cervical cancer aggressiveness. CRISPR/Cas9 CD55 knockout; ectopic HPV-E6 expression; flow cytometry of CD55+ subpopulations; sphere formation assay; in vitro and in vivo tumourigenicity assay; radiation treatment assay The Journal of pathology Medium 28944962
2020 ST3GAL1-mediated O-linked sialylation of CD55 is required for CD55's immune-evasion function in breast cancer. ST3GAL1 silencing shifted the O-glycan profile of CD55 from disialylated core 2 to nonsialylated core 1 structures without affecting N-glycans. O-desialylation of CD55 resulted in increased C3 deposition, increased complement-mediated lysis, and enhanced sensitivity to antibody-dependent cell-mediated cytotoxicity. ST3GAL1 siRNA knockdown; tandem mass spectrometry of N- and O-linked oligosaccharides of CD55; C3 deposition assay; complement-mediated lysis assay; ADCC assay Cancer immunology research High 33177111
2021 CD55 on human erythrocytes is specifically required for internalization of Plasmodium falciparum parasites, not for pre-invasion kinetics, erythrocyte deformability, or echinocytosis. CRISPR-Cas9 editing to ablate CD55, antibody-based inhibition, and live cell imaging showed that parasites attached normally to CD55-null erythrocytes but entry was inhibited. CD55 acts after rhoptry discharge and appears to play a role in stability and/or progression of the moving junction. CRISPR-Cas9 editing of erythrocyte CD55; antibody-based inhibition; live cell imaging; deformability and echinocytosis assays eLife High 34028351
2016 CD55 is a transcriptional target of HIF-2α in neuroblastoma cells. HIF-2α expression is sufficient to sustain stem-like features, while CD55 protein specifically contributes to colony growth and cell invasion but not stemness. CD55-positive populations display pro-invading and anti-adhesive properties. HIF-2α gain-of-function; CD55 functional characterization in CD55-positive vs CD55-negative subpopulations; colony formation and invasion assays Oncogenesis Medium 27043658
2016 HIF-1α negatively regulates CD55 expression in airway epithelial cells. Hypoxia down-regulated CD55 on small-airway epithelial cells in vitro and in murine lungs in vivo, associated with local complement activation. Pharmacologic inhibition or siRNA silencing of HIF-1α during hypoxia recovered CD55 expression; HIF-1α overexpression down-regulated CD55. Pharmacologic HIF-1α inhibition; HIF-1α gene silencing; HIF-1α overexpression; in vivo murine hypoxia model; complement activation assay American journal of respiratory cell and molecular biology High 27494303
2022 EGFR/Wnt signaling induces β-catenin-mediated lncRNA LINC00973 expression, which sponges miR-216b (targeting CD55) and miR-150 (targeting CD59), resulting in upregulated CD55/CD59 that suppresses the complement system and CD8+ T cell activation. CD55/CD59-neutralizing antibody treatment or LINC00973 promoter mutation activated complement and CD8+ T cells and inhibited tumor growth; combined anti-CD55/CD59 and anti-PD-1 treatment showed synergistic tumor-inhibiting effects. EGFR/Wnt/β-catenin pathway manipulation; LINC00973 promoter mutation; miRNA sponging mechanism validation; complement activation assay; CD8+ T cell activation assay; antibody neutralization; anti-PD-1 combination therapy in vivo Nature cancer High 36271172
2019 Bee venom upregulates CD55 mRNA and protein in THP-1 cells via ERK phosphorylation. CD55 induction by bee venom inactivates complement as measured by C3 convertase activity. In an AD mouse model, CD55 was decreased and C3C/MAC were elevated; bee venom treatment reversed these changes and alleviated AD symptoms. mRNA/protein expression analysis; ERK phosphorylation assay; complement-dependent cytotoxicity assay; bacteria-killing assay; in vivo AD mouse model with bee venom treatment Toxins Medium 31027358
2006 CD55 (DAF) promotes CD1d expression on macrophages during CVB3 H3 infection and is required for activation of Vγ4+ T cells that mediate myocarditis. DAF-/- mice showed reduced CD1d expression and few Vγ4+IFNγ+ cells; the immunopathogenic mechanism differs in DAF-/- animals (CD8+ T cell depletion aggravates rather than protects disease), establishing CD55 as required for the CD1d/Vγ4+ T cell pathway of CVB3-induced myocarditis. DAF-/- mouse infection model; CD1d expression analysis; Vγ4+ T cell depletion; CD8+ T cell depletion; IFN-γ intracellular staining Viral immunology Medium 16817758
2002 VEGF upregulates CD55 expression at the cell surface and within the extracellular matrix of endothelial cells (HUVEC). MMP-7 releases intact, functionally active CD55 from ECM, whereas papain degrades it and collagenase fails to release it, establishing that metalloproteinase-mediated shedding generates soluble functional CD55 in the tumor environment. VEGF stimulation of HUVEC; flow cytometry; ECM CD55 quantification; complement functional assay; protease treatment (papain, collagenase, MMP-7) of ECM-bound CD55 Tissue antigens Medium 12445304

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2012 TOR signaling and rapamycin influence longevity by regulating SKN-1/Nrf and DAF-16/FoxO. Cell metabolism 520 22560223
2003 Transcriptional outputs of the Caenorhabditis elegans forkhead protein DAF-16. Aging cell 332 12882324
2000 daf-12 encodes a nuclear receptor that regulates the dauer diapause and developmental age in C. elegans. Genes & development 316 10859169
1994 daf-2, daf-16 and daf-23: genetically interacting genes controlling Dauer formation in Caenorhabditis elegans. Genetics 288 8056303
2003 Antigen-presenting cell exosomes are protected from complement-mediated lysis by expression of CD55 and CD59. European journal of immunology 287 12645951
2013 PQM-1 complements DAF-16 as a key transcriptional regulator of DAF-2-mediated development and longevity. Cell 242 23911329
2005 Overlapping and distinct functions for a Caenorhabditis elegans SIR2 and DAF-16/FOXO. Mechanisms of ageing and development 205 16280150
1998 daf-12 regulates developmental age and the dauer alternative in Caenorhabditis elegans. Development (Cambridge, England) 203 9477318
2005 The complement inhibitory protein DAF (CD55) suppresses T cell immunity in vivo. The Journal of experimental medicine 195 15710649
2017 DAF-16/FOXO Transcription Factor in Aging and Longevity. Frontiers in pharmacology 186 28878670
2006 Worming pathways to and from DAF-16/FOXO. Experimental gerontology 161 16839734
2020 DAF-16/FoxO in Caenorhabditis elegans and Its Role in Metabolic Remodeling. Cells 157 31906434
2006 The search for DAF-16/FOXO transcriptional targets: approaches and discoveries. Experimental gerontology 156 16934425
2010 A new DAF-16 isoform regulates longevity. Nature 155 20613724
2017 CD55 Deficiency, Early-Onset Protein-Losing Enteropathy, and Thrombosis. The New England journal of medicine 150 28657829
1994 Structure and function of decay accelerating factor CD55. The Journal of laboratory and clinical medicine 147 7511675
2013 Redox-dependent control of FOXO/DAF-16 by transportin-1. Molecular cell 134 23333309
1999 Expression of the activation antigen CD97 and its ligand CD55 in rheumatoid synovial tissue. Arthritis and rheumatism 113 10211878
1996 The HeLa cell receptor for enterovirus 70 is decay-accelerating factor (CD55). Journal of virology 103 8764022
2012 Human CD55 expression blocks hyperacute rejection and restricts complement activation in Gal knockout cardiac xenografts. Transplantation 99 22391577
2001 CD55 is over-expressed in the tumour environment. British journal of cancer 85 11139317
2006 Serotonin targets the DAF-16/FOXO signaling pathway to modulate stress responses. Cell metabolism 84 17141627
2006 The role of complement regulatory proteins (CD55 and CD59) in the pathogenesis of autoimmune hemocytopenias. Autoimmunity reviews 84 17289551
2018 Beyond the Role of CD55 as a Complement Component. Immune network 82 29503741
2017 CD55 regulates self-renewal and cisplatin resistance in endometrioid tumors. The Journal of experimental medicine 76 28838952
1991 Association of the CD59 and CD55 cell surface glycoproteins with other membrane molecules. Journal of immunology (Baltimore, Md. : 1950) 76 1715364
2014 DAF-16 target identification in C. elegans: past, present and future. Biogerontology 74 25156270
2022 Silencing EGFR-upregulated expression of CD55 and CD59 activates the complement system and sensitizes lung cancer to checkpoint blockade. Nature cancer 70 36271172
1998 Cardiovirulent coxsackieviruses and the decay-accelerating factor (CD55) receptor. Virology 67 9601501
2022 Intestine-specific removal of DAF-2 nearly doubles lifespan in Caenorhabditis elegans with little fitness cost. Nature communications 65 36284093
2018 DAF-16: FOXO in the Context of C. elegans. Current topics in developmental biology 64 29433733
2021 Sulforaphane promotes C. elegans longevity and healthspan via DAF-16/DAF-2 insulin/IGF-1 signaling. Aging 63 33471780
2009 Dynamin- and lipid raft-dependent entry of decay-accelerating factor (DAF)-binding and non-DAF-binding coxsackieviruses into nonpolarized cells. Journal of virology 56 19710132
2005 daf-7 and the development of Strongyloides ratti and Parastrongyloides trichosuri. Molecular and biochemical parasitology 55 15664656
1996 Identification of insect cell lines by DNA amplification fingerprinting (DAF). Insect molecular biology 55 8799737
1999 Protein carbonyl accumulation in aging dauer formation-defective (daf) mutants of Caenorhabditis elegans. The journals of gerontology. Series A, Biological sciences and medical sciences 52 10051850
2001 DAF-16-dependent and independent expression targets of DAF-2 insulin receptor-like pathway in Caenorhabditis elegans include FKBPs. Journal of molecular biology 50 11743719
1992 Expression of the DAF (CD55) and CD59 antigens during normal hematopoietic cell differentiation. Journal of leukocyte biology 50 1281489
2020 Sialylation of CD55 by ST3GAL1 Facilitates Immune Evasion in Cancer. Cancer immunology research 49 33177111
2002 Expression of the EGF-TM7 receptor CD97 and its ligand CD55 (DAF) in multiple sclerosis. Journal of neuroimmunology 49 12417446
2010 Deletion of either CD55 or CD97 ameliorates arthritis in mouse models. Arthritis and rheumatism 48 20131275
2015 dbl-1/TGF-β and daf-12/NHR Signaling Mediate Cell-Nonautonomous Effects of daf-16/FOXO on Starvation-Induced Developmental Arrest. PLoS genetics 47 26656736
1999 Molecular and functional analysis of mouse decay accelerating factor (CD55). The Biochemical journal 47 10417349
2019 Effects of Lycium barbarum Polysaccharides on Health and Aging of C. elegans Depend on daf-12/daf-16. Oxidative medicine and cellular longevity 46 31583041
2014 Ins-4 and daf-28 function redundantly to regulate C. elegans L1 arrest. Developmental biology 45 25128585
2014 Cell-nonautonomous effects of dFOXO/DAF-16 in aging. Cell reports 44 24508462
2015 The nuclear receptor DAF-12 regulates nutrient metabolism and reproductive growth in nematodes. PLoS genetics 43 25774872
2006 Complement decay accelerating factor (DAF)/CD55 in cancer. Cancer immunology, immunotherapy : CII 43 16485129
2021 Neuronal DAF-16-to-intestinal DAF-16 communication underlies organismal lifespan extension in C. elegans. iScience 42 34235410
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
2022 CD55 in cancer: Complementing functions in a non-canonical manner. Cancer letters 38 36216147
2006 The expression and action of decay-accelerating factor (CD55) in human malignancies and cancer therapy. Cellular oncology : the official journal of the International Society for Cellular Oncology 38 17167176
2006 Decay-accelerating factor (CD55): a versatile acting molecule in human malignancies. Biochimica et biophysica acta 37 16784816
2010 Expression of CD55 and CD59 on peripheral blood cells from systemic lupus erythematosus (SLE) patients. Cellular immunology 35 20727519
2000 Expression of complement regulatory proteins CR1, DAF, MCP and CD59 in haematological malignancies. European journal of haematology 34 10680700
2020 Sentinel lymph node detection in oral cancer: a within-patient comparison between [99mTc]Tc-tilmanocept and [99mTc]Tc-nanocolloid. European journal of nuclear medicine and molecular imaging 33 32839855
2008 Terminal Continuation (TC) RNA amplification enables expression profiling using minute RNA input obtained from mouse brain. International journal of molecular sciences 32 19165351
2021 DAF-16/FoxO and DAF-12/VDR control cellular plasticity both cell-autonomously and via interorgan signaling. PLoS biology 30 33891586
2018 DAF-21/Hsp90 is required for C. elegans longevity by ensuring DAF-16/FOXO isoform A function. Scientific reports 30 30104664
2004 Expression of CD97 and CD55 in human medullary thyroid carcinomas. International journal of oncology 29 14719104
2017 Human papillomavirus E6 protein enriches the CD55(+) population in cervical cancer cells, promoting radioresistance and cancer aggressiveness. The Journal of pathology 28 28944962
2016 Functional Conservation and Divergence of daf-22 Paralogs in Pristionchus pacificus Dauer Development. Molecular biology and evolution 28 27189572
2022 Lonicera japonica polysaccharides improve longevity and fitness of Caenorhabditis elegans by activating DAF-16. International journal of biological macromolecules 27 36586650
2017 Calycosin promotes lifespan in Caenorhabditis elegans through insulin signaling pathway via daf-16, age-1 and daf-2. Journal of bioscience and bioengineering 27 28434978
2015 The Deubiquitylase MATH-33 Controls DAF-16 Stability and Function in Metabolism and Longevity. Cell metabolism 27 26154057
2002 The role of CD55 in protecting the tumour environment from complement attack. Tissue antigens 27 12445304
2023 Luteolin promotes pathogen resistance in Caenorhabditis elegans via DAF-2/DAF-16 insulin-like signaling pathway. International immunopharmacology 26 36640711
2015 CD55 deposited on synovial collagen fibers protects from immune complex-mediated arthritis. Arthritis research & therapy 26 25596646
2017 Neuronal functions of FOXO/DAF-16. Nutrition and healthy aging 25 28447066
2001 A DAF-1-binding protein BRA-1 is a negative regulator of DAF-7 TGF-beta signaling. Proceedings of the National Academy of Sciences of the United States of America 25 11353865
1977 Tc-99m methylene diphosphonate versus Tc-99m pyrophosphate: biologic and clinical comparison. Journal of nuclear medicine : official publication, Society of Nuclear Medicine 25 197133
2021 Erythrocyte CD55 mediates the internalization of Plasmodium falciparum parasites. eLife 24 34028351
2008 Molecular cloning and DNA binding characterization of DAF-16 orthologs from Ancylostoma hookworms. International journal for parasitology 24 18930062
2005 Review: Cromer and DAF: role in health and disease. Immunohematology 24 15954803
2020 DAF-16 and SMK-1 Contribute to Innate Immunity During Adulthood in Caenorhabditis elegans. G3 (Bethesda, Md.) 23 32161087
2020 The precursor of PI(3,4,5)P3 alleviates aging by activating daf-18(Pten) and independent of daf-16. Nature communications 23 32901024
2013 A DAF-16/FoxO3a-dependent longevity signal is initiated by antioxidants. BioFactors (Oxford, England) 23 24123695
1994 Distribution of C3-step regulatory proteins of the complement system, CD35 (CR1), CD46 (MCP), and CD55 (DAF), in hematological malignancies. Leukemia & lymphoma 21 7514063
2021 Barley β-glucan resist oxidative stress of Caenorhabditis elegans via daf-2/daf-16 pathway. International journal of biological macromolecules 20 34798183
2016 Parainfluenza virus 5 upregulates CD55 expression to produce virions with enhanced resistance to complement-mediated neutralization. Virology 20 27505156
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
2016 Comparison of the radiotoxicity of the 99mTc-labeled compounds 99mTc-pertechnetate, 99mTc-HMPAO and 99mTc-MIBI. International journal of radiation biology 19 27117205
2002 Detection of CD55- and/or CD59-deficient red cell populations in patients with plasma cell dyscrasias. International journal of hematology 19 11843289
2018 MPK-1/ERK pathway regulates DNA damage response during development through DAF-16/FOXO. Nucleic acids research 18 29788264
2016 Distinct CD55 Isoform Synthesis and Inhibition of Complement-Dependent Cytolysis by Hepatitis C Virus. Journal of immunology (Baltimore, Md. : 1950) 18 27357152
1998 Signal transduction via a protein associated with a glycosylphosphatidylinositol-anchored protein, decay-accelerating factor (DAF/CD55). International immunology 18 9620603
2021 Phosphatidylcholine mediates the crosstalk between LET-607 and DAF-16 stress response pathways. PLoS genetics 17 34014977
2017 Inhibitory effect of trans-caryophyllene (TC) on leukocyte-endothelial attachment. Toxicology and applied pharmacology 17 28624443
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
2019 Bee Venom Alleviates Atopic Dermatitis Symptoms through the Upregulation of Decay-Accelerating Factor (DAF/CD55). Toxins 16 31027358
2014 Expression of CD55 on red blood cells of β-thalassemia patients. Hemoglobin 16 25026028
2011 Expression of complement regulatory proteins CD55, CD59, CD35, and CD46 in rheumatoid arthritis. Revista brasileira de reumatologia 16 21953001
2019 Somatostatin receptor targeting with hydrophilic [99mTc/186Re]Tc/Re-tricarbonyl NODAGA and NOTA complexes. Nuclear medicine and biology 15 31129499
2016 Hypoxia-Inducible Factor-1α Regulates CD55 in Airway Epithelium. American journal of respiratory cell and molecular biology 15 27494303
2012 DAF/CD55 and Protectin/CD59 modulate adaptive immunity and disease outcome in experimental autoimmune myasthenia gravis. Journal of neuroimmunology 15 22325826
2023 Role of PDGFRA+ cells and a CD55+ PDGFRALo fraction in the gastric mesenchymal niche. Nature communications 14 38042929
2016 CD55 is a HIF-2α marker with anti-adhesive and pro-invading properties in neuroblastoma. Oncogenesis 14 27043658
2010 Identification of hookworm DAF-16/FOXO response elements and direct gene targets. PloS one 14 20808816
2006 Decay-accelerating factor (CD55) promotes CD1d expression and Vgamma4+ T-cell activation in coxsackievirus B3-induced myocarditis. Viral immunology 14 16817758

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