Affinage

CR1

Complement receptor type 1 · UniProt P17927

Length
2039 aa
Mass
223.7 kDa
Annotated
2026-04-28
100 papers in source corpus 30 papers cited in narrative 30 extracted findings

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

CR1 (CD35) is a multi-ligand complement regulatory receptor that integrates opsonin recognition, complement inactivation, immune complex clearance, and immunomodulatory signaling across diverse cell types. Its extracellular domain contains tandem short consensus repeat (SCR) modules organized into long homologous repeats (LHRs) that harbor distinct ligand-binding sites: Site 1 (SCR 1–4) and Site 2 (SCR 8–9) bind C3b and C4b with specificity determined by as few as two residues, while CCP24–25 in LHR-D constitutes a shared binding site for C1q and MBL, enabling CR1 to recognize all major complement opsonins (PMID:8175757, PMID:8757632, PMID:11955431, PMID:9324355, PMID:29563915). CR1 serves as a cofactor for factor I–mediated cleavage of C3b/C4b and accelerates decay of the alternative pathway C3 convertase C3bBb by engaging specific residues on the Bb von Willebrand factor type A domain, thereby potently suppressing complement amplification on host surfaces (PMID:11694537, PMID:26260209). On erythrocytes, CR1 mediates immune adherence by clustering through FAP-1 scaffolding and ATP-dependent increases in membrane lipid mobility, transporting opsonized immune complexes to tissue macrophages via an Fc receptor– and protease-dependent transfer mechanism (PMID:18684861, PMID:24022490, PMID:10657648). In leukocytes, CR1 ligation triggers cell-type-specific responses: PLD activation and Ca²⁺ mobilization in neutrophils to promote phagocytosis, IL-1β release from monocytes, inhibitory signaling that suppresses B and T lymphocyte proliferation and cytokine production, and it additionally serves as a receptor for EBV on B cells and for P. falciparum invasion of erythrocytes (PMID:8326130, PMID:2136879, PMID:11884446, PMID:16360013, PMID:23416052, PMID:21251929).

Mechanistic history

Synthesis pass · year-by-year structured walk · 16 steps
  1. 1986 High

    The discovery that CR1 undergoes PKC-dependent phosphorylation selectively in phagocytes but not lymphocytes or erythrocytes established that CR1 is not merely a passive binding receptor but participates in cell-type-specific intracellular signaling linked to phagocytic activation.

    Evidence 32PO₄ metabolic labeling and immunoprecipitation in neutrophils, monocytes, eosinophils, B cells, and erythrocytes after PMA/FMLP stimulation

    PMID:3484510

    Open questions at the time
    • The specific phosphorylation site(s) on CR1's cytoplasmic tail were not identified
    • Downstream signaling effectors of phosphorylated CR1 were not mapped
    • Whether phosphorylation regulates ligand binding affinity was not tested
  2. 1991 High

    Mapping the minimal C3b-binding domain to SCRs 1–4 of LHR-B and demonstrating that a bivalent chimeric construct reconstitutes full factor I cofactor and alternative pathway regulatory activity defined the modular architecture underlying CR1's complement control function.

    Evidence CR1/CR2 chimeric receptor expression on COS and K562 cells, ¹²⁵I-pC3b binding (Kd ~1.8 nM), factor I cofactor and AP inhibition assays

    PMID:1836011

    Open questions at the time
    • Contribution of LHR-A vs LHR-C sites not resolved
    • Structural basis for bivalency-dependent activity enhancement not determined
  3. 1993 High

    Demonstrating that CR1 cross-linking on neutrophils activates PLD, mobilizes Ca²⁺, and generates diglyceride — while CR3 mediates engulfment — resolved the division of labor between complement receptors in phagocytosis and established CR1 as a signaling-competent receptor.

    Evidence Anti-CR1/CR3 antibody blockade during phagocytosis of complement-opsonized yeast, PLD activation, Ca²⁺ mobilization, and diglyceride production assays

    PMID:8326130

    Open questions at the time
    • The signaling intermediates between CR1 ligation and PLD activation were not identified
    • Whether CR1 signaling requires its cytoplasmic tail phosphorylation was not tested
  4. 1994 High

    Systematic substitution mutagenesis defined two functionally distinct C3b/C4b binding sites on CR1 (Site 1 at SCR 1–2 for C4b; Site 2 at SCR 8–9 for C3b and C4b) and showed that cofactor activity requires no sequences beyond binding modules, establishing the principle of modular self-sufficiency in complement regulation.

    Evidence Substitution mutagenesis of CR1 constructs with C3b/C4b binding and factor I cofactor assays

    PMID:8175757

    Open questions at the time
    • Whether the two sites act cooperatively on a single C3b/C4b molecule was not resolved
    • Cofactor activity kinetics not quantified for individual sites
  5. 1994 High

    Identification of CR1 as the sole C3 receptor on glomerular podocytes, combined with the finding that functional CR1 is released on membrane vesicles into urine, revealed an unexpected non-hematopoietic site of complement regulation with implications for immune complex handling in the kidney.

    Evidence Frozen kidney section adherence assays, immunoprecipitation from surface-labeled glomeruli, ultracentrifugation and EM of urinary vesicles, allotype discordance in transplant recipients

    PMID:2418113 PMID:8113681

    Open questions at the time
    • The physiological role of podocyte-derived CR1 vesicles in glomerular immune complex clearance was not established in vivo
    • Whether urinary CR1 vesicles retain cofactor activity was not tested
  6. 1996 High

    Two amino acid substitutions (Ser37→Tyr, Gly79→Asp) were shown to convert a C4b-only site into a dual C3b/C4b site, revealing that ligand specificity between the homologous binding sites is determined by minimal residue differences — explaining how gene duplication and divergence generated functional diversity within CR1.

    Evidence Site-directed mutagenesis of truncated CR1, transfection into K562 cells, rosette binding assays with EC3b and EC4b

    PMID:8757632

    Open questions at the time
    • Structural basis for how these residues contact C3b vs C4b was not resolved at atomic level
  7. 1997 High

    The finding that CR1 binds C1q directly with nanomolar affinity, in addition to C3b and C4b, established CR1 as a receptor for all three major complement opsonins and explained its role in immune adherence of classical pathway–activated immune complexes.

    Evidence Radioligand binding on CR1-transfected K562 cells, immobilized rsCR1 assays, surface plasmon resonance (Keq ~3.9 nM), competition with C3b dimers and C1q collagen domain

    PMID:9324355

    Open questions at the time
    • The C1q binding site on CR1 was not mapped in this study
    • Whether C1q and C3b/C4b co-engage CR1 simultaneously in physiological immune complexes was not demonstrated
  8. 1998 High

    Pulse-chase experiments with mutant CR1 constructs mapped soluble CR1 generation to proteolytic cleavage within the C-terminal transmembrane domain of fully glycosylated, surface-expressed CR1, while complementary studies identified PMNs as the predominant source and showed inflammatory stimuli accelerate release — defining a regulated shedding pathway.

    Evidence Pulse-chase metabolic labeling of wild-type and mutant/chimeric CR1 in COS cells; intracellular-domain-specific ELISA on PMNs, monocytes, and T cells with fMLP/TNFα/LPS stimulation

    PMID:7957565 PMID:9405292

    Open questions at the time
    • The responsible protease was not identified
    • Physiological function of circulating sCR1 remains unclear
  9. 2000 High

    Demonstrating that immune complex transfer from erythrocytes to macrophages requires Fc receptor engagement and results in removal of CR1 from the erythrocyte surface explained the progressive loss of erythrocyte CR1 observed in immune complex diseases and defined a two-receptor (CR1 + FcR) transfer mechanism.

    Evidence In vitro transfer assay with P388D1 macrophages using bispecific mAb-linked bacteriophage, Ficoll separation, RIA, flow cytometry, Fab vs intact IgG comparison

    PMID:10657648

    Open questions at the time
    • Whether the CR1 proteolysis during transfer uses the same cleavage site as sCR1 shedding was not determined
    • In vivo kinetics of erythrocyte CR1 loss during transfer not measured
  10. 2001 High

    Mutagenesis of factor B's type A domain revealed that CR1 and DAF share a decay acceleration mechanism targeting α-helices 4–5 of Bb, distinct from factor H's mechanism at the α1 helix, clarifying how multiple host regulators target the same convertase through partially overlapping but distinct molecular contacts.

    Evidence Site-directed mutagenesis of factor B, C3bBb assembly, decay acceleration assays with CR1, DAF, and factor H

    PMID:11694537

    Open questions at the time
    • No structural model of CR1–C3bBb complex was obtained
    • Whether CR1 and DAF compete for the same Bb surface was not directly tested
  11. 2002 High

    The atomic-resolution structure of CR1 modules 15–17 combined with mutagenesis identified a positively charged surface on module 15 for C4b binding and basic residues on module 16 for C3b binding, providing the first structural framework for understanding how the linear SCR architecture presents distinct ligand-binding surfaces.

    Evidence NMR/crystal structure of CCP 15–17 (residues 901–1095), structure-guided mutagenesis, functional binding assays

    PMID:11955431

    Open questions at the time
    • No co-crystal structure of CR1 with C3b or C4b was obtained
    • Structural basis for cofactor vs decay-accelerating activities at this site not resolved
  12. 2002 High

    Showing that CR1-selective ligation on B cells with multimeric C3(H2O) inhibits proliferation and suppresses anti-IgM-induced Ca²⁺ transients established CR1 as an independent inhibitory receptor on B lymphocytes, separate from the well-known CR2 costimulatory pathway.

    Evidence B cell proliferation assays, intracellular Ca²⁺ measurement, protein phosphorylation analysis using CR1-selective multimeric C3(H2O)

    PMID:11884446

    Open questions at the time
    • The signaling pathway downstream of CR1 that mediates B cell inhibition was not identified
    • Whether CR1 inhibitory signaling requires its cytoplasmic tail was not tested
  13. 2008 High

    Identification of FAP-1 as a cytoplasmic scaffolding partner for CR1's PDZ motifs on erythrocytes explained how ligation-induced CR1 clustering is organized and how erythrocytes avoid phagocytosis while transferring immune complexes.

    Evidence PDZ-peptide array, co-immunoprecipitation, detergent fractionation, flow cytometry and fluorescence microscopy on erythrocytes

    PMID:18684861

    Open questions at the time
    • Whether FAP-1 is required for CR1 clustering in vivo was not demonstrated
    • Other cytoskeletal linkers or adaptors connecting CR1 to the erythrocyte membrane skeleton were not identified
  14. 2013 High

    The finding that CR1 ligation on erythrocytes triggers ATP release, which increases membrane lipid mobility and promotes CR1 clustering and macrophage phagocytosis of immune-adherent complexes, revealed an autocrine signaling loop that enhances immune adherence avidity on anucleate cells.

    Evidence Luminometric ATP release assay, membrane fluidity measurements, CR1 clustering assay, phagocytosis assay on human erythrocytes

    PMID:24022490

    Open questions at the time
    • The channel or transporter mediating ATP release from erythrocytes upon CR1 ligation was not identified
    • Whether this mechanism operates in vivo during immune complex clearance is unknown
  15. 2013 High

    Demonstrating that CR1 on B cells functions as an independent EBV receptor — mediating gp350/220 binding and latent infection when HLA class II is co-expressed — expanded the known viral entry pathways beyond CD21 and identified CR1 as a physiologically relevant alternative EBV receptor.

    Evidence Lentiviral transduction of CD21-negative pre-B and myeloid lines with CD35 ± CD21 ± HLA II, gp350/220 binding, EBV latent infection assay

    PMID:23416052

    Open questions at the time
    • The gp350 binding site on CR1 was not mapped
    • Whether CR1-mediated EBV entry occurs in primary B cells in vivo was not confirmed
  16. 2018 High

    Mapping both MBL and C1q binding to the same CR1 bimodular fragment CCP24–25 in LHR-D unified the recognition of lectin and classical pathway initiators on a single receptor region, while subsidiary C1q contacts on globular heads explained partial binding independence.

    Evidence Recombinant CCP24–25 and deletion variants, competitive binding assays with MBL, ficolin-2, and C1q

    PMID:29563915

    Open questions at the time
    • Whether ficolin-2 binding to CR1 is functionally significant was not resolved
    • No structural model of the CCP24–25–C1q/MBL interface exists

Open questions

Synthesis pass · forward-looking unresolved questions
  • Key unresolved questions include the identity of the protease that cleaves CR1's transmembrane domain to generate sCR1, the structural basis for CR1's dual decay-accelerating and cofactor activities at atomic resolution, the signaling intermediates linking CR1 ligation to inhibitory responses in lymphocytes, and the in vivo contribution of CR1-mediated ATP signaling on erythrocytes to immune complex clearance.
  • Transmembrane protease identity unknown
  • No co-crystal structure of CR1 with any ligand
  • CR1 inhibitory signaling pathway in lymphocytes uncharacterized
  • In vivo validation of erythrocyte ATP-dependent clustering mechanism lacking

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0098772 molecular function regulator activity 4 GO:0060090 molecular adaptor activity 3 GO:0001618 virus receptor activity 2
Localization
GO:0005886 plasma membrane 6 GO:0005576 extracellular region 3 GO:0005856 cytoskeleton 1
Pathway
R-HSA-168256 Immune System 9 R-HSA-162582 Signal Transduction 4 R-HSA-1643685 Disease 4
Partners
C1QC3BC4BCFBCFIFAP-1MBLPFEMP1

Evidence

Reading pass · 30 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1997 CR1 (CD35) binds C1q directly; biotinylated/radioiodinated C1q bound specifically to CR1-transfected K562 cells and immobilized recombinant soluble CR1 (rsCR1), with binding inhibitable by unlabeled C1q collagen domain and partially by C3b dimers. Surface plasmon resonance yielded an apparent Keq of 3.9 nM, identifying CR1 as a cellular C1q receptor recognizing all three complement opsonins (C1q, C3b, C4b). Radioligand binding on transfected cells, immobilized rsCR1 binding assay, surface plasmon resonance (BIAcore), inhibition studies Immunity High 9324355
2000 CR1 (CD35) functions as a cellular receptor for mannan-binding lectin (MBL); radioiodinated MBL bound immobilized soluble CR1 with Kd ~5 nM, C1q inhibited MBL binding (suggesting overlapping sites), MBL binding to PMNs correlated with CR1 expression, and CR1 mediated erythrocyte adhesion to immobilized MBL and phagocytosis of MBL-IgG opsonized bacteria. Radioligand binding to immobilized sCR1, competitive inhibition assay, PMN binding assay with CR1-correlated expression, erythrocyte adhesion assay, phagocytosis assay The Journal of experimental medicine High 11120776
1999 C1q and C4b bind independently and additively to CR1 to support erythrocyte immune adherence; C1q, C4b, and C3b binding to immobilized CR1 are independent events by BIAcore analysis, and a single C1q binding site resides on LHR-D of CR1. Tip-plate erythrocyte adhesion assay, BIAcore binding analysis, inhibition with anti-CR1 Fab fragments Journal of immunology High 10528211
2002 The crystal/NMR structure of complement control protein modules 15-17 of CR1 (residues 901-1095) revealed the principal C3b/C4b binding site in an extended head-to-tail arrangement with flexibility at the 16-17 junction; structure-guided mutagenesis identified a positively charged surface region on module 15 critical for C4b binding, and basic side chains of module 16 on the same face required for C3b binding. NMR structure determination, structure-guided site-directed mutagenesis, functional binding assays Cell High 11955431
1994 Functional analysis by substitution mutagenesis defined two C3b/C4b binding sites on CR1: Site 1 (SCR-1,2) binds C4b and acts as cofactor for C4b cleavage; Site 2 (SCR-8,9) binds iC3/C3b and C4b and acts as cofactor for cleavage of both. Cofactor activity for C4b cleavage is greater at Site 2 than Site 1. No sequences beyond those required for binding were necessary for cofactor activity. Substitution mutagenesis of CR1 constructs, C3b/C4b binding assays, factor I-cofactor activity assays The Journal of biological chemistry High 8175757
1991 The C3b binding site of CR1 requires SCRs 1-4 of a long homologous repeat (LHR), with SCR 1 and SCR 3 most critical; a (CR1)2-F(ab')2 chimeric protein retaining SCRs 1-4 of LHR-B binds pC3b (Kd ~1.8 nM), acts as factor I cofactor, and inhibits alternative pathway activation, demonstrating that bivalent expression of these SCRs reconstitutes full regulatory function. CR1/CR2 chimeric receptor expression on COS and K562 cells, 125I-pC3b binding (Kd determination), factor I-cofactor assays, alternative pathway inhibition assay The Journal of experimental medicine High 1836011
2001 CR1 (along with DAF and factor H) decays the AP C3 convertase C3bBb by interacting with specific sites on the type A domain of factor B; mutations at alpha-helices 4 and 5 of Bb (Gln-335, Tyr-338, Ser-339, Asp-382) conferred resistance to DAF- and CR1-mediated (but not factor H-mediated) decay acceleration, while mutations at the alpha1 helix (D254G) conferred resistance to all three regulators. Site-directed mutagenesis of factor B, C3bBb assembly, decay acceleration assays with DAF, CR1, and factor H The Journal of biological chemistry High 11694537
1986 CR1 undergoes protein kinase C-dependent phosphorylation selectively in phagocytic cells (neutrophils, monocytes, eosinophils) upon PMA or FMLP stimulation, but not in B lymphocytes, SB cells, or erythrocytes, indicating cell-type-specific regulation of CR1 by phosphorylation linked to phagocytic activation. 32PO4 metabolic labeling, PMA/FMLP stimulation, immunoprecipitation, SDS-PAGE autoradiography The Journal of experimental medicine High 3484510
1993 CR1 cross-linking on human neutrophils activates phospholipase D (PLD), mobilizes intracellular Ca2+, and contributes to diglyceride production, demonstrating that CR1 initiates transmembrane signaling linked to phagocytosis of complement-opsonized particles; CR1 primarily promotes particle adhesion while CR3 mediates subsequent engulfment. Anti-CR1/CR3 antibody blockade, complement-opsonized yeast phagocytosis assay, PLD activation assay, intracellular Ca2+ mobilization measurement, diglyceride production assay Journal of immunology High 8326130
2013 CR1 (CD35) on B cells serves as an independent EBV receptor; CD35-transduced CD21-negative cells bound gp350/220 and became latently EBV-infected when the fusion receptor HLA class II was co-expressed, with infection kinetics and biophysical characteristics distinct from CD21-mediated infection. Lentiviral transduction of CD21-negative pre-B and myeloid lines with CD35 ± CD21 ± HLA II; gp350/220 binding assay; EBV latent infection assay (p24/latency markers) Cell reports High 23416052
2008 On resting erythrocytes CR1 is dispersed (not clustered) and partitions to the cytoskeleton upon detergent solubilization; CR1's cytoplasmic tail PDZ motifs bind PDZ domains 2, 3, and 5 of the scaffolding protein FAP-1, which is expressed on circulating erythrocytes. Ligation-induced CR1 clustering requires FAP-1 association and localizes the opsonic stimulus to prevent erythrocyte phagocytosis during immune-complex transfer. Detergent fractionation, PDZ-peptide array, co-immunoprecipitation, flow cytometry, fluorescence microscopy Blood High 18684861
2013 Ligation of CR1 on human red blood cells triggers ATP release via a Ca2+- and enzyme-independent mechanism; released ATP increases lipid fraction mobility of RBC membranes, facilitates CR1 clustering and enhances binding avidity for complement-opsonized particles, and stimulates macrophage phagocytosis of immune-adherent complexes. Luminometric and fluorescence-based ATP release assay, membrane fluidity measurements, CR1 clustering assay, phagocytosis assay The Journal of biological chemistry High 24022490
1998 Soluble CR1 (sCR1) in plasma is generated by proteolytic cleavage within the C-terminal region of the CR1 transmembrane domain; pulse-chase experiments with mutated and chimeric CR1 constructs in COS cells showed that (1) sCR1 arises by proteolysis, (2) the cleavage site is within the transmembrane domain C-terminus, (3) the substrate is fully glycosylated CR1, and (4) cleavage occurs in late secretory vesicles or at the plasma membrane. Pulse-chase metabolic labeling, transient expression of mutant/chimeric CR1 in COS cells, comparison of sCR1 vs membrane CR1 sizes The Biochemical journal High 9405292
1994 Soluble CR1 in plasma is released from cell-surface CR1 by proteolytic surface cleavage (lacking the intracellular domain); PMNs are the predominant source of plasma sCR1, with release accelerated by fMLP, TNF-α, and LPS, and sustained by GM-CSF; T lymphocyte lines do not release sCR1. Intracellular-domain-specific ELISA (mCR1-ELISA), cell culture release assays with various stimuli, cell-type comparison European journal of immunology High 7957565
2002 CR1 binds directly to Plasmodium falciparum erythrocyte membrane protein 1 (PfEMP1), the major rosetting adhesin; this interaction mediates rosetting of infected erythrocytes to uninfected erythrocytes via CR1 on the uninfected cell. Binding assays with PfEMP1 and CR1 constructs (literature review synthesis in Trends paper, citing primary data) Trends in molecular medicine Medium 12421687
2011 CR1 on erythrocytes mediates sialic-acid-independent invasion of P. falciparum field isolates; anti-CR1 antibodies and soluble CR1 nearly completely blocked invasion of neuraminidase-treated erythrocytes and partially inhibited invasion of intact erythrocytes across eight Kenyan field isolates. Erythrocyte invasion assay with neuraminidase-treated cells, anti-CR1 antibody and sCR1 inhibition, eight P. falciparum field isolates Molecular and biochemical parasitology High 21251929
2002 CR1 mediates inhibitory signaling in human B lymphocytes; clustering CR1 with multimeric C3b-like C3 (which binds CR1 but not CR2) inhibited B cell proliferation even in the presence of IL-2/IL-15, and suppressed anti-IgM-induced intracellular Ca2+ transients and cytoplasmic protein phosphorylation. B cell proliferation assay, intracellular Ca2+ measurement, protein phosphorylation analysis; multimeric C3(H2O) as CR1-selective ligand Journal of immunology High 11884446
2006 CR1 on T lymphocytes mediates inhibitory signals; anti-CR1 antibodies profoundly inhibited T cell proliferation, suppressed protein synthesis of IFN-γ and IL-2 (without affecting immediate-early gene transcription), and reduced expression of PCNA and cyclins A and D3, indicating post-transcriptional inhibition of cell cycle progression. T cell proliferation assay, cytokine mRNA and protein analysis, PCNA/cyclin expression analysis, anti-CR1 antibody stimulation Molecular immunology Medium 16360013
2015 Co-ligation of CR1 (CD35) and CD46 on activated CD4+ T cells enhances CD25 expression, granzyme B production, cell proliferation, IL-10 secretion, and reduces IFN-γ release, promoting regulatory T cell development; CR1 expression was identified on activated CD4+ T cells in tonsillar inter-follicular regions. Co-ligation experiments with anti-CD35 and anti-CD46 antibodies, flow cytometry for surface markers, ELISA for cytokines, immunohistochemistry of tonsils Immunology letters Medium 25742728
1990 CR1 on human monocytes mediates induction of IL-1α, IL-1β production and IL-1β release upon stimulation with polymerized C3b or anti-CR1 antibody; monomeric C3b induced only cell-associated IL-1 without secretion; IL-1 production correlated with CR1 expression levels and was dissociated from LPS contamination. Monocyte culture in serum-free conditions with polymyxin B, IL-1 bioassay and RIA, anti-CR1 antibody stimulation, correlation of CR1 expression with response Journal of immunology High 2136879
2000 Transfer of CR1-bound immune complexes from erythrocytes to macrophages requires Fc receptor engagement; experiments using phiX174 bacteriophage bound via bispecific mAb (heteropolymer) showed that all three components (phiX174, HP, and CR1) were removed from erythrocytes and internalized by macrophages, with transfer abrogated when only Fab (no Fc) fragments were used, implying Fc receptor-mediated close juxtaposition followed by proteolytic CR1 cleavage. In vitro transfer assay with P388D1 macrophages, Ficoll separation, RIA and flow cytometry probing of both cell types, Fab vs intact IgG comparison Journal of immunology High 10657648
1996 Two specific amino acid substitutions (Tyr for Ser37 in CP1 and Asp for Gly79 in CP2) together, but not individually, convert the C4b-only binding site of CR1 into a site that binds both C3b and C4b, demonstrating that these two residues at homologous positions are determinants of C3b vs. C4b specificity. Site-directed mutagenesis of truncated CR1, transfection into K562 cells, erythrocyte rosette binding assays with EC3b and EC4b Journal of immunology High 8757632
2015 CR1 on epithelial cells (CHO cell model) reduces C3b deposition by ~80% during classical pathway activation and >95% during alternative pathway activation, primarily via decay accelerating activity; deposited C4b/C3b are cleaved with t½ ~30 min by CR1-dependent cofactor activity; CR1 works intrinsically (only on the cell expressing it) and binds but does not internalize C4b/C3b-opsonized immune complexes. CHO cell expression system, complement activation assays (classical and alternative pathways), C3b deposition measurement, cofactor cleavage kinetics, intrinsic vs. extrinsic activity testing, immune complex binding/internalization assays Molecular immunology High 26260209
2018 Both MBL and C1q interact with CR1 through the same pair of modules, CCP24-25, located in LHR-D; CR1 bimodular fragment CCP24-25 and deletion variants were used to map this site; C1q binding to CR1 shares a main common interaction site on collagen stalks with MBL but also has subsidiary sites on C1q globular heads distinct from MBL. Production of CR1 CCP24-25 and deletion variants in eukaryotic cells, binding assays with MBL, ficolin-2, and C1q, competitive binding analysis Frontiers in immunology High 29563915
1996 CR1 ligation on CD4+ T cells via cross-linked anti-CR1 or aggregated C3b enhances HIV replication (viral gene transcription, p24, RT activity) in infected cells, an effect specific to CR1 and abrogated by soluble recombinant CR1; CR2 ligation had no effect. HIV infection of normal CD4+ T cells in vitro, CR1 ligation with cross-linked antibodies or aggregated C3b, p24 ELISA, RT activity assay, rescue with soluble rCR1 Clinical and experimental immunology Medium 8918576
1987 CR1 mRNA exhibits a size polymorphism that correlates with the allelic molecular weight polymorphism of the CR1 protein; RNA blot analysis of EBV-transformed cell lines expressing each allelic variant showed distinct transcript sizes corresponding to the protein size variants, consistent with the polymorphism being determined at the genomic level (possibly via unequal crossing-over in homologous repeat segments). CR1 purification, HPLC tryptic peptide sequencing, oligonucleotide probe design, Northern blot of EBV-transformed cell lines expressing allelic variants PNAS Medium 3031685
1996 Mac-1 (CR3) and CR1 cooperate to mediate efficient adhesion of complement-opsonized Leishmania major metacyclic promastigotes to macrophages; CR1's factor I cofactor activity converts C3b to iC3b, which then stably binds Mac-1, making Mac-1 the predominant receptor for phagocytosis while CR1 promotes adhesion but not phagocytosis itself. Complement receptor blockade with specific antibodies, purified receptor cell-free binding system, transfected cell lines expressing individual receptors, bovine monocytes lacking Mac-1 as genetic model, phagocytosis assay Infection and immunity High 8675328
1994 CR1 on glomerular podocytes is the sole C3 receptor in the human kidney; it is characterized as the C3b/C4b (CR1) receptor by functional adherence assays, anti-CR1-selective inhibition, and immunoprecipitation from surface-labeled glomerular membranes, with a variant of Mr 160,000 (in addition to the common 205,000 form) observed in some individuals. Frozen kidney section complement adherence assay with defined C3-fragment-coated erythrocytes, immunofluorescence with CR1/CR2/CR3-specific antibodies, detergent solubilization, 125I surface labeling, immunoprecipitation, SDS-PAGE Journal of immunology High 2418113
1994 CR1-coated membrane vesicles are released from glomerular podocytes into urine; urinary CR1 is membrane-bound (pellets at 200,000 g, enriched in cholesterol/phospholipids, visualized as vesicles by EM), functionally binds C3b-coated immune complexes, is 15 kDa larger than erythrocyte CR1, and carries alleles discordant with erythrocyte CR1 in transplant recipients (confirming renal origin). Ultracentrifugation, sucrose density gradient, gel filtration, cholesterol/phospholipid analysis, electron microscopy of immunoaffinity-purified material, C3b-IC binding assay, allotype discordance in transplant recipients The Journal of experimental medicine High 8113681
1993 Erythrocyte CR1 functions as a dynamic buffering system for opsonized immune complexes; transfer of IC between erythrocytes is related to CR1 concentration of both donor and recipient cells (fastest from low- to high-CR1 cells); in the absence of factor I, IC partition according to relative CR1 numbers with no release into solution, while in serum, factor I-dependent processing allows progressive IC release for macrophage transfer. Differential agglutination to separate RBC populations by blood group, immune complex transfer assay with 125I-labeled complexes, factor I-depleted serum experiments Clinical and experimental immunology Medium 2968204

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
1982 Complement receptor (CR1) deficiency in erythrocytes from patients with systemic lupus erythematosus. The Journal of experimental medicine 333 6978375
2009 Fractalkine and CX 3 CR1 regulate hippocampal neurogenesis in adult and aged rats. Neurobiology of aging 288 20018408
1985 Human follicular dendritic cells express CR1, CR2, and CR3 complement receptor antigens. Journal of immunology (Baltimore, Md. : 1950) 233 2411809
1997 Complement receptor type 1 (CR1, CD35) is a receptor for C1q. Immunity 188 9324355
2000 Complement receptor 1/CD35 is a receptor for mannan-binding lectin. The Journal of experimental medicine 185 11120776
2010 Replication of CLU, CR1, and PICALM associations with alzheimer disease. Archives of neurology 178 20554627
2007 Complement receptors CD21 and CD35 in humoral immunity. Immunological reviews 141 17850488
1986 Tissue-specific phosphorylation of complement receptors CR1 and CR2. The Journal of experimental medicine 125 3484510
1993 Signaling properties of CR3 (CD11b/CD18) and CR1 (CD35) in relation to phagocytosis of complement-opsonized particles. Journal of immunology (Baltimore, Md. : 1950) 120 8326130
2013 Human complement receptor type 1/CD35 is an Epstein-Barr Virus receptor. Cell reports 108 23416052
2011 Complement receptor 1 (CR1) and Alzheimer's disease. Immunobiology 95 21840620
2002 Structure of the C3b binding site of CR1 (CD35), the immune adherence receptor. Cell 95 11955431
1994 Analysis of the functional domains of complement receptor type 1 (C3b/C4b receptor; CD35) by substitution mutagenesis. The Journal of biological chemistry 89 8175757
1991 Mapping of the C3b-binding site of CR1 and construction of a (CR1)2-F(ab')2 chimeric complement inhibitor. The Journal of experimental medicine 88 1836011
2013 Blockage of CR1 prevents activation of rodent microglia. Neurobiology of disease 79 23454195
1992 Levels of complement regulatory proteins, CD35 (CR1), CD46 (MCP) and CD55 (DAF) in human haematological malignancies. British journal of haematology 78 1384649
1994 Identification of membrane-bound CR1 (CD35) in human urine: evidence for its release by glomerular podocytes. The Journal of experimental medicine 76 8113681
1995 A Ca2+/calmodulin kinase inhibitor, KN-62, inhibits neurite outgrowth stimulated by CAMs and FGF. Molecular and cellular neurosciences 75 7599959
2000 Inhibition of CaM kinase II activation and force maintenance by KN-93 in arterial smooth muscle. American journal of physiology. Cell physiology 73 10712242
2014 CR1 in Alzheimer's disease. Molecular neurobiology 72 24794147
2002 Complement receptor type 1 (CD35) mediates inhibitory signals in human B lymphocytes. Journal of immunology (Baltimore, Md. : 1950) 69 11884446
2008 Comparative functional evolution of human and mouse CR1 and CR2. Journal of immunology (Baltimore, Md. : 1950) 67 18713965
1987 Monoclonal antibodies to the human C3b/C4b receptor (CR1) enhance specific B cell differentiation. Journal of immunology (Baltimore, Md. : 1950) 65 2952731
2012 Genetic association of CR1 with Alzheimer's disease: a tentative disease mechanism. Neurobiology of aging 63 22819390
2000 A role for CD21/CD35 and CD19 in responses to acute septic peritonitis: a potential mechanism for mast cell activation. Journal of immunology (Baltimore, Md. : 1950) 62 11120817
1996 Leishmania major-human macrophage interactions: cooperation between Mac-1 (CD11b/CD18) and complement receptor type 1 (CD35) in promastigote adhesion. Infection and immunity 62 8675328
2009 The structure, genetic polymorphisms, expression and biological functions of complement receptor type 1 (CR1/CD35). Immunopharmacology and immunotoxicology 60 19874218
1999 C1q and C4b bind simultaneously to CR1 and additively support erythrocyte adhesion. Journal of immunology (Baltimore, Md. : 1950) 57 10528211
1993 Circulating soluble CR1 (CD35). Serum levels in diseases and evidence for its release by human leukocytes. Journal of immunology (Baltimore, Md. : 1950) 53 8335953
2014 Genotype patterns at CLU, CR1, PICALM and APOE, cognition and Mediterranean diet: the PREDIMED-NAVARRA trial. Genes & nutrition 51 24643340
1987 Human complement C3b/C4b receptor (CR1) mRNA polymorphism that correlates with the CR1 allelic molecular weight polymorphism. Proceedings of the National Academy of Sciences of the United States of America 51 3031685
2001 Heteropolymer-mediated clearance of immune complexes via erythrocyte CR1: mechanisms and applications. Immunological reviews 50 11782244
1990 Induction of IL-1 release through stimulation of the C3b/C4b complement receptor type one (CR1, CD35) on human monocytes. Journal of immunology (Baltimore, Md. : 1950) 49 2136879
1989 Human liver Kupffer cells express CR1, CR3, and CR4 complement receptor antigens. An immunohistochemical study. Laboratory investigation; a journal of technical methods and pathology 49 2478758
2006 The complement receptor 1, CR1 (CD35), mediates inhibitory signals in human T-lymphocytes. Molecular immunology 47 16360013
2001 Decay-accelerating factor (DAF), complement receptor 1 (CR1), and factor H dissociate the complement AP C3 convertase (C3bBb) via sites on the type A domain of Bb. The Journal of biological chemistry 47 11694537
1998 CD21/CD35 in B cell activation. Seminars in immunology 47 9695184
1990 Characterization of CR1- and membrane cofactor protein-like proteins of two primates. Journal of immunology (Baltimore, Md. : 1950) 46 2140391
1993 Evidence for the role of CR1 (CD35), in addition to CR2 (CD21), in facilitating infection of human T cells with opsonized HIV. Scandinavian journal of immunology 45 8346417
1986 Characterization of the human glomerular C3 receptor as the C3b/C4b complement type one (CR1) receptor. Journal of immunology (Baltimore, Md. : 1950) 45 2418113
1989 Proliferation of resting B cells is modulated by CR2 and CR1. Immunology letters 44 2527816
1996 A functional analysis of recombinant soluble CD46 in vivo and a comparison with recombinant soluble forms of CD55 and CD35 in vitro. European journal of immunology 43 8605924
1994 Soluble complement receptor type 1 (CD35) is released from leukocytes by surface cleavage. European journal of immunology 43 7957565
1988 Immune complexes and erythrocyte CR1 (complement receptor type 1): effect of CR1 numbers on binding and release reactions. Clinical and experimental immunology 38 2968204
2022 Age is no barrier for adults undergoing HCT for AML in CR1: contemporary CIBMTR analysis. Bone marrow transplantation 37 35368040
2015 Role of complement receptor 1 (CR1; CD35) on epithelial cells: A model for understanding complement-mediated damage in the kidney. Molecular immunology 34 26260209
2002 Human complement receptor type 1 (CR1) binds to a major malarial adhesin. Trends in molecular medicine 34 12421687
2000 Expression of complement regulatory proteins CR1, DAF, MCP and CD59 in haematological malignancies. European journal of haematology 34 10680700
2012 Implication of common and disease specific variants in CLU, CR1, and PICALM. Neurobiology of aging 32 22402018
1999 Stimulators of the cAMP cascade reverse amnesia induced by intra-amygdala but not intrahippocampal KN-62 administration. Neurobiology of learning and memory 32 9889075
2015 Alzheimer's disease is associated with low density of the long CR1 isoform. Neurobiology of aging 30 25666996
2000 Transfer of immune complexes from erythrocyte CR1 to mouse macrophages. Journal of immunology (Baltimore, Md. : 1950) 30 10657648
1990 Correlation between erythrocyte CR1 reduction and other blood proteinase markers in patients with malignant and inflammatory disorders. Blood 30 2158365
1989 Expression of complement receptors type 1 (CR1) and type 3 (CR3) on circulating granulocytes in experimentally provoked asthma. The Journal of allergy and clinical immunology 30 2926084
2009 CR1 levels and gene polymorphisms exhibit differential association with falciparum malaria in regions of varying disease endemicity. Human immunology 29 19480840
2004 Reduced complement receptor 1 (CR1, CD35) transcription in systemic lupus erythematosus. Molecular immunology 29 15163541
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
1999 Targeting of influenza epitopes to murine CR1/CR2 using single-chain antibodies. Immunopharmacology 28 10408376
2017 The Multifaceted Personality of Intestinal CX3CR1+ Macrophages. Trends in immunology 27 28844811
1990 Loss of human CR1- and murine Crry-like exons in human CR2 transcripts due to CR2 gene mutations. Journal of immunology (Baltimore, Md. : 1950) 27 2144008
1986 Defective complement receptors (CR1 and CR3) on erythrocytes and leukocytes of factor I (C3b-inactivator) deficient patients. Clinical and experimental immunology 27 2949901
2011 Plasmodium falciparum field isolates use complement receptor 1 (CR1) as a receptor for invasion of erythrocytes. Molecular and biochemical parasitology 26 21251929
2006 Consumption of erythrocyte CR1 (CD35) is associated with protection against systemic lupus erythematosus renal flare. Clinical and experimental immunology 26 16412051
2000 Immunomodulatory functions of murine CR1/2. Immunopharmacology 26 10904111
2011 CLU, CR1 and PICALM genes associate with Alzheimer's-related senile plaques. Alzheimer's research & therapy 25 21466683
2003 Regulation of B-cell activation by complement receptors CD21 and CD35. Current pharmaceutical design 25 12871189
1997 Role of knot (kn) in wing patterning in Drosophila. Genetics 25 9383063
1992 The binding of immune complexes by the erythrocyte complement receptor 1 (CR1). Immunopharmacology 25 1473961
1990 Deficiencies of human C3 complement receptors type 1 (CR1, CD35) and type 2 (CR2, CD21). Immunodeficiency reviews 25 2164822
2013 CR1-mediated ATP release by human red blood cells promotes CR1 clustering and modulates the immune transfer process. The Journal of biological chemistry 24 24022490
2008 Ligation of erythrocyte CR1 induces its clustering in complex with scaffolding protein FAP-1. Blood 24 18684861
2000 Regulation of humoral immune responses by CD21/CD35. Immunological reviews 23 11043778
1996 Structural polymorphisms of complement receptor 1 (CR1) in systemic lupus erythematosus (SLE) patients and normal controls of three ethnic groups. Clinical and experimental immunology 23 8706338
1994 Binding of C3b and C4b by the CR1-like site in murine CR1. Journal of immunology (Baltimore, Md. : 1950) 23 8144890
1998 Soluble form of complement C3b/C4b receptor (CR1) results from a proteolytic cleavage in the C-terminal region of CR1 transmembrane domain. The Biochemical journal 22 9405292
1998 Soluble complement receptor type 1 (CD35) in bronchoalveolar lavage of inflammatory lung diseases. The European respiratory journal 22 9543279
1997 The role of complement receptor type 1 (CR1, CD35) in determining the cellular distribution of opsonized immune complexes between whole blood cells: kinetic analysis of the buffering capacity of erythrocytes. Immunology 22 9038723
1990 Nonsteroidal antiinflammatory agents inhibit upregulation of CD11b, CD11c, and CD35 in neutrophils stimulated by formyl-methionine-leucine-phenylalanine. Inflammation 22 2138999
2015 Complement receptor type 1 (CR1/CD35) expressed on activated human CD4+ T cells contributes to generation of regulatory T cells. Immunology letters 21 25742728
2015 Production of ginsenoside F1 using commercial enzyme Cellulase KN. Journal of ginseng research 21 27158232
2014 Expression of CD44 and CD35 during normal and myelodysplastic erythropoiesis. Leukemia research 21 25582385
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
1989 The human C3b receptor (CR1). Advances in nephrology from the Necker Hospital 21 2522267
2018 C1q and Mannose-Binding Lectin Interact with CR1 in the Same Region on CCP24-25 Modules. Frontiers in immunology 20 29563915
2007 Splenic CD19-CD35+B220+ cells function as an inducer of follicular dendritic cell network formation. Blood 20 17519390
2010 High CR1 level and related polymorphic variants are associated with cerebral malaria in eastern-India. Infection, genetics and evolution : journal of molecular epidemiology and evolutionary genetics in infectious diseases 19 20951238
1987 C3b receptor (CR1) expression on the polymorphonuclear leukocytes from patients with systemic lupus erythematosus. Clinical and experimental immunology 19 2955969
2013 Lack of association of CR1, PICALM and CLU gene polymorphisms with Alzheimer disease in a Polish population. Neurologia i neurochirurgia polska 18 23650005
2011 Implication of CD21, CD35, and CD55 in the pathogenesis of age-related macular degeneration. American journal of ophthalmology 18 21669404
1999 Role of complement receptors CD21/CD35 in B lymphocyte activation and survival. Current topics in microbiology and immunology 18 10396040
1997 The roles of complement receptors type 1 (CR1, CD35) and type 3 (CR3, CD11b/CD18) in the regulation of the immune complex-elicited respiratory burst of polymorphonuclear leukocytes in whole blood. European journal of immunology 18 9394818
1996 Substitution of two amino acids confers C3b binding to the C4b binding site of CR1 (CD35). Analysis based on ligand binding by chimpanzee erythrocyte complement receptor. Journal of immunology (Baltimore, Md. : 1950) 17 8757632
1994 Lowered expression of C3b receptor (CR1) on erythrocytes of rheumatoid arthritis patients. Immunobiology 17 7806259
1994 Erythropoietin therapy in humans increases erythrocyte expression of complement receptor type 1 (CD35). Journal of the American Society of Nephrology : JASN 17 8068876
2022 Mitigation of Negative Effects of Chromium (VI) Toxicity in Faba Bean (Vicia faba) Plants through the Supplementation of Kinetin (KN) and Gibberellic Acid (GA3). Plants (Basel, Switzerland) 16 36501342
2015 Apoptosis induced by NAD depletion is inhibited by KN-93 in a CaMKII-independent manner. Experimental cell research 16 26024774
2011 The E3 CR1-gamma gene in human adenoviruses associated with epidemic keratoconjunctivitis. Virus research 16 21683743
2011 Expression of complement regulatory proteins CD55, CD59, CD35, and CD46 in rheumatoid arthritis. Revista brasileira de reumatologia 16 21953001
1996 Ligation of CR1 (C3b receptor, CD35) on CD4+ T lymphocytes enhances viral replication in HIV-infected cells. Clinical and experimental immunology 16 8918576
1993 The anti-lipid A antibody HA-1A binds to rough gram-negative bacteria, fixes complement and facilitates binding to erythrocyte CR1 (CD35). Clinical and experimental immunology 16 8485908