Affinage

CR1

Complement receptor type 1 · UniProt P17927

Length
2039 aa
Mass
223.7 kDa
Annotated
2026-06-09
100 papers in source corpus 28 papers cited in narrative 28 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

CR1 (CD35) is a modular complement regulatory glycoprotein that restrains complement activation through two complementary enzymatic activities — decay-acceleration of the C3 and C5 convertases and cofactor activity for factor I-mediated cleavage of C3b and C4b (PMID:2972794, PMID:8175757, PMID:26260209). Its ligand-binding architecture is organized into discrete sites: an N-terminal Site 1 (CCPs 1–3) that mediates C4b binding and convertase decay, and a Site 2 (CCPs 8–10 and 15–17) that binds both C3b and C4b and supports their factor I-dependent cleavage (PMID:8175757, PMID:16177096). Specificity within these modules is governed by defined residues — the principal C3b/C4b-binding module pair adopts an extended head-to-tail arrangement in which a basic surface patch on module 15/16 contacts the acidic α'-chain segment of C3b, and two substitutions in CCP1/CCP2 are sufficient to convert a C4b-binding site into a C3b-binding one (PMID:11955431, PMID:9988761, PMID:8757632). CR1 also serves as a receptor for the defense collagens C1q and MBL, both binding a single CCP24–25 module pair in LHR-D, thereby mediating erythrocyte adhesion and phagocytosis of opsonized particles (PMID:9324355, PMID:11120776, PMID:29563915). Beyond complement regulation, CR1 is an active signaling receptor: ligand engagement or antibody cross-linking on phagocytes triggers phospholipase D activation, Ca2+ mobilization, NF-κB translocation, and IL-1 production, whereas clustering on B and T lymphocytes delivers inhibitory signals that suppress proliferation and cytokine synthesis (PMID:8326130, PMID:2136879, PMID:7594489, PMID:11884446, PMID:16360013). CR1 is expressed on erythrocytes, phagocytes, lymphocytes, glomerular podocytes, and hypoxic endothelium, and is released both as proteolytically cleaved soluble CR1 from neutrophils and as membrane vesicles shed by podocytes into urine (PMID:3484510, PMID:7957565, PMID:8113681, PMID:9950773, PMID:2418113). It additionally functions as a CD4-independent entry receptor for complement-opsonized HIV and as an EBV receptor distinct from CD21 (PMID:23416052, PMID:7682158).

Mechanistic history

Synthesis pass · year-by-year structured walk · 22 steps
  1. 1986 High

    Established that CR1 is the sole C3b receptor on glomerular podocytes with intrinsic convertase decay activity, extending its role beyond circulating cells to a tissue-resident regulator.

    Evidence Rosette adherence, immunofluorescence, convertase decay assay and surface immunoprecipitation on human glomeruli from three donors

    PMID:2418113

    Open questions at the time
    • Did not define which CCP modules mediate podocyte C3b binding
    • Physiological consequence of podocyte CR1 loss not addressed
  2. 1986 High

    Showed CR1 undergoes cell-type-restricted phosphorylation, linking the receptor to active signaling specifically in phagocytes.

    Evidence 32PO4 metabolic labeling and immunoprecipitation after PMA/FMLP stimulation across phagocytic and non-phagocytic cells

    PMID:3484510

    Open questions at the time
    • Kinase identity not directly demonstrated
    • Phosphorylated cytoplasmic residues not mapped
  3. 1988 High

    Resolved the molecular basis of ligand specificity by mapping distinct C4b and C3b recognition sites to the N-terminal SCRs of separate LHRs, defining CR1 as a multivalent regulator.

    Evidence Deletion mutagenesis of full-length CR1 in COS cells with rosetting and factor I cofactor assays

    PMID:2972794

    Open questions at the time
    • Atomic-level contacts not defined
    • Quantitative affinities for each site not measured
  4. 1992 Medium

    Characterized CR1 as a more potent factor I cofactor for C4b than C3b, distinguishing it functionally from MCP.

    Evidence In vitro reconstituted cofactor cleavage of fluid-phase and liposome-bound C4b with pH and detergent titration

    PMID:1386357

    Open questions at the time
    • Single-lab in vitro reconstitution
    • Cellular relevance of dual pH optima unresolved
  5. 1994 High

    Refined the two-site model, defining Site 1 (CCP1-2) as C4b-specific cofactor and Site 2 (CCP8-9) as a dual C3b/C4b site, and showed modifications could augment both activities.

    Evidence Substitution mutagenesis in COS cells with ligand binding and cofactor cleavage readouts

    PMID:8175757

    Open questions at the time
    • Did not establish convertase decay contributions of each site
    • Mechanism of activity enhancement unexplained
  6. 1994 Medium

    Pinpointed the acidic C3b α'-chain residues required for CR1 engagement, mapping the complement-side of the interface and distinguishing CR1 from factor H and MCP contact regions.

    Evidence Site-directed mutagenesis of C3 with factor I cofactor cleavage as surrogate binding readout

    PMID:7963581

    Open questions at the time
    • Direct binding affinities not measured
    • Used cofactor activity as proxy for binding
  7. 1994 Medium

    Determined that two point substitutions in CCP1/CCP2 are sufficient to graft C3b binding onto a C4b site, defining the residue determinants of ligand discrimination.

    Evidence Site-directed mutagenesis of truncated CR1 with rosetting and cofactor assays

    PMID:8757632

    Open questions at the time
    • Structural basis of the gained interaction not shown
    • Single-lab functional readouts
  8. 1994 Medium

    Showed murine CR1 collapses C3b and C4b recognition into a single SCR-1-dependent site, contrasting the multi-site human architecture.

    Evidence Murine CR1/human CR2 chimeric deletion constructs in K562 cells with rosetting

    PMID:8144890

    Open questions at the time
    • No quantitative affinity comparison to human CR1
    • Cofactor activity of murine site not tested
  9. 1994 Medium

    Identified soluble plasma CR1 as a proteolytic ectodomain product shed predominantly by neutrophils under inflammatory stimuli, defining a regulated release mechanism.

    Evidence Intracellular-domain-specific ELISA, SDS-PAGE size comparison and RT-PCR after PMN stimulation

    PMID:7957565

    Open questions at the time
    • Protease responsible not identified
    • Cleavage site not mapped
  10. 1994 High

    Showed podocyte CR1 is shed into urine as functional membrane vesicles, establishing a distinct vesicular release route from the proteolytic neutrophil pathway.

    Evidence Ultracentrifugation, lipid analysis, EM, renal transplant allotype discordance and C3b-binding assay

    PMID:8113681

    Open questions at the time
    • Mechanism of vesicle formation not defined
    • Functional fate of urinary CR1 unknown
  11. 1997 High

    Identified CR1 as a high-affinity C1q receptor binding via the collagen domain, expanding its repertoire beyond C3/C4 fragments.

    Evidence Radioligand binding to CR1-transfected K562 cells and SPR on immobilized rsCR1 with competition assays

    PMID:9324355

    Open questions at the time
    • CR1 module mediating C1q binding not localized in this study
    • Cellular consequence of C1q engagement not addressed
  12. 1999 Medium

    Extended the C3b acidic interface to residues 738–767 and showed CR1 contacts a wider segment than factor H, refining the convertase-regulator binding map.

    Evidence Charged-residue mutagenic scan of C3 with cofactor cleavage assays for CR1, factor H and MCP

    PMID:9988761

    Open questions at the time
    • No co-structure of the CR1–C3b interface
    • Proxy assay rather than direct binding
  13. 1999 Medium

    Demonstrated hypoxia induces functional CR1 on endothelial cells, identifying a regulated context-dependent expression site relevant to vascular complement control.

    Evidence ELISA, confocal colocalization, Western blot, in situ hybridization and cofactor activity in HUVECs

    PMID:9950773

    Open questions at the time
    • Predominantly intracellular localization fate unclear
    • In vivo relevance not established
  14. 2000 High

    Identified CR1 as an MBL receptor sharing a binding site with C1q, linking it to lectin-pathway recognition and phagocytosis of opsonized bacteria.

    Evidence Radioligand binding to immobilized sCR1, competition with C1q, erythrocyte adhesion and PMN phagocytosis assays

    PMID:11120776

    Open questions at the time
    • Precise binding module not localized in this study
    • Signaling downstream of MBL engagement not defined
  15. 2002 High

    Provided the structure of the principal C3b/C4b-binding module trio, revealing an extended flexible arrangement and the basic surface patches required for ligand contact.

    Evidence NMR structure of CCP15-17 with structure-guided mutagenesis and binding assays

    PMID:11955431

    Open questions at the time
    • No structure of CR1 bound to C3b/C4b
    • Full-length receptor architecture not resolved
  16. 2002 Medium

    Defined CR1 as a negative regulator of B cell activation, showing ligand clustering inhibits BCR-driven proliferation and calcium signaling.

    Evidence Aggregated C3/C3(H2O) stimulation of tonsil B cells with proliferation, Ca2+ and phosphoprotein readouts

    PMID:11884446

    Open questions at the time
    • Cytoplasmic signaling effectors not identified
    • Single-lab antibody/ligand approach
  17. 2005 Medium

    Dissected the spatial logic of convertase decay, showing Site 1 mediates dissociation while Site 2 binds C3b, and that tandem Site 1 copies act synergistically, implying a dimeric convertase target.

    Evidence Site mutant and tandem constructs with decay-accelerating activity assays for C3 and C5 convertases

    PMID:16177096

    Open questions at the time
    • Proposed convertase dimer not structurally confirmed
    • Single-lab functional assays
  18. 2006 Medium

    Established CR1 as an inhibitory T cell receptor acting downstream of immediate-early transcription to block cytokine protein synthesis and cell-cycle entry.

    Evidence Anti-CR1 stimulation of T cells with proliferation, RT-PCR and protein expression readouts

    PMID:16360013

    Open questions at the time
    • Translational/post-transcriptional mechanism not defined
    • Physiological ligand in T cell context unclear
  19. 2013 High

    Identified CR1 as an EBV entry receptor distinct from CD21, broadening its role in viral tropism.

    Evidence Retroviral transduction of CD21-negative cell lines with gp350/220 binding and latent infection readouts

    PMID:23416052

    Open questions at the time
    • CR1 module mediating gp350 binding not mapped
    • In vivo contribution to EBV infection unknown
  20. 2015 Medium

    Quantified the intrinsic, non-internalizing protective action of epithelial CR1, showing strong reduction of C3b deposition by decay-acceleration plus progressive cofactor cleavage.

    Evidence CHO podocyte model with classical/alternative pathway deposition, cleavage kinetics and internalization assays

    PMID:26260209

    Open questions at the time
    • Model cell system rather than primary podocytes
    • Single-lab study
  21. 2015 Medium

    Showed CR1 co-ligation with CD46 on CD4+ T cells drives a regulatory phenotype, implicating CR1 in adaptive immune tolerance.

    Evidence Anti-CR1/anti-CD46 co-ligation with cytokine ELISA, flow cytometry and tonsil immunohistochemistry

    PMID:25742728

    Open questions at the time
    • Mechanistic crosstalk between CR1 and CD46 signaling not defined
    • Antibody co-ligation rather than natural ligand
  22. 2018 Medium

    Localized both C1q and MBL binding to a single CCP24–25 module pair in LHR-D, unifying the defense-collagen recognition site and distinguishing C1q (collagen plus head sites) from MBL (collagen only).

    Evidence CR1 deletion variants (isolated CCP24-25; CCP22-30 lacking CCP24-25) with binding and competition assays

    PMID:29563915

    Open questions at the time
    • No co-structure of CR1 with C1q or MBL
    • Single-lab study

Open questions

Synthesis pass · forward-looking unresolved questions
  • How CR1 ligand engagement is transduced into the distinct activating (phagocyte) versus inhibitory (lymphocyte) intracellular signals, including the kinases and cytoplasmic effectors involved, remains unresolved.
  • No defined cytoplasmic signaling adaptors identified
  • PKC isoform and phosphosites not mapped
  • No structure of CR1 in complex with its complement or collagen ligands

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0060089 molecular transducer activity 4 GO:0098772 molecular function regulator activity 4 GO:0038024 cargo receptor activity 3 GO:0001618 virus receptor activity 2
Localization
GO:0005576 extracellular region 3 GO:0005886 plasma membrane 3
Pathway
R-HSA-162582 Signal Transduction 4 R-HSA-168256 Immune System 4
Partners
C1QC3BC4BCD46CFIMBL

Evidence

Reading pass · 28 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1988 CR1 contains distinct C3b and C4b recognition sites: the NH2-terminal two SCRs of LHR-A determine C4b specificity, while the NH2-terminal two SCRs of LHR-B and LHR-C each contain a C3b binding site. Recombinant full-length CR1 expressed in COS cells mediates rosette formation with C4b- and C3b-coated erythrocytes and has factor I-cofactor activity for C3(ma) cleavage. Deletion mutagenesis of cDNA constructs expressed in COS cells; rosette formation assay; factor I-cofactor activity assay The Journal of experimental medicine High 2972794
1997 CR1 (CD35) functions as a cellular receptor for C1q. Biotinylated/radioiodinated C1q binds specifically to CR1-transfected K562 cells and to immobilized recombinant soluble CR1 (rsCR1). The C1q collagen domain mediates binding, and C3b dimers partially inhibit binding. Surface plasmon resonance in physiological saline yielded an apparent equilibrium dissociation constant of 3.9 nM. Radioligand binding to transfected K562 cells; SPR kinetics with immobilized rsCR1; inhibition assays with collagen domain fragments and C3b dimers Immunity High 9324355
2000 CR1/CD35 functions as a cellular receptor for mannan-binding lectin (MBL). Radioiodinated MBL binds immobilized soluble CR1 with an apparent equilibrium dissociation constant of ~5 nM. The MBL carbohydrate-binding site is not involved (N-acetyl-d-glucosamine does not inhibit binding). C1q competes with MBL for the same or adjacent CR1 binding site. CR1 mediates erythrocyte adhesion to immobilized MBL and functions as a phagocytic receptor on PMNs for MBL-IgG-opsonized bacteria. Radioligand binding to immobilized sCR1; competition assays; erythrocyte adhesion assay; phagocytosis assay on PMNs The Journal of experimental medicine High 11120776
2002 The principal C3b/C4b binding site of CR1 (modules 15–17, residues 901–1095) adopts an extended head-to-tail arrangement with flexibility at the module 16–17 junction. Structure-guided mutagenesis identified a positively charged surface patch on module 15 critical for C4b binding, and basic side chains on module 16 (on the same face) required for both C3b and C4b binding. NMR structure determination of CCP modules 15–17; structure-guided mutagenesis with functional binding assays Cell High 11955431
1994 CR1 has two distinct ligand-binding sites: Site 1 (SCR-1 and SCR-2) binds C4b and is cofactor for C4b cleavage; Site 2 (SCR-8 and SCR-9) binds both iC3/C3b and C4b and is cofactor for cleavage of both. Cofactor activity maps entirely to sequences required for binding. Modifications to either site can increase activity for both ligands. Substitution mutagenesis of CR1 constructs expressed in COS cells; ligand binding assays; factor I-cofactor cleavage assays The Journal of biological chemistry High 8175757
1986 CR1 undergoes tissue-specific phosphorylation: PMA and FMLP induce phosphorylation of CR1 in phagocytic cells (neutrophils, monocytes, eosinophils) but not in non-phagocytic cells (B lymphocytes, erythrocytes). CR1 phosphorylation is associated with activation of phagocytic function. CR3 and FcR are not phosphorylated under the same conditions. 32PO4 metabolic labeling; immunoprecipitation and SDS-PAGE autoradiography; PMA/FMLP stimulation The Journal of experimental medicine High 3484510
1993 CR1 cross-linking in human neutrophils activates phospholipase D (PLD) and triggers transient intracellular Ca2+ mobilization. CR1 mediates adhesion of complement-opsonized particles but also participates in engulfment signaling. PMA potentiates CR1-induced PLD activation while impairing phospholipase C activation. Anti-CR1 antibody cross-linking; diacylglycerol and PLD activity assays; intracellular Ca2+ fluorometry; phagocytosis assays with anti-receptor antibodies Journal of immunology Medium 8326130
2013 CR1 (CD35) functions as an independent EBV receptor on B cells distinct from CD21. CD35-transduced CD21-negative pre-B and myeloid leukemia cells bind EBV gp350/220 and become latently infected when the fusion receptor HLA II is co-expressed. The temporal, biophysical, and structural characteristics of CD35-mediated EBV infection are distinct from CD21-mediated infection. Retroviral transduction of CD21-negative cell lines with CD35, CD21, or both; gp350/220 binding assay; viral infection/latency assay Cell reports High 23416052
1990 Stimulation of CR1 on human monocytes with multivalent polymerized C3b or C3b-Sepharose induces production and release of IL-1β. Monomeric C3b induces intracellular IL-1 but not release. Anti-CR1 antibody also triggers IL-1 production. IL-1 production correlates with CR1 expression levels, establishing CR1-dependent signaling as a pathway to IL-1 induction. C3b-Sepharose stimulation of adherent monocytes; ELISA and bioassay for IL-1α and IL-1β; inhibition with anti-CR1 antibody; serum-free conditions with LPS controls Journal of immunology Medium 2136879
1995 CR1 triggering on HIV-infected monocytic cells induces nuclear translocation of NF-κB (p50/p65) and enhances HIV replication 2–4-fold. CR1 stimulation with F(ab')2 anti-CR1 antibodies or C3 fragments on uninfected monocytes also induces NF-κB translocation comparable to TNF-α stimulation. F(ab')2 anti-CR1 antibody and C3 fragment stimulation; NF-κB nuclear translocation assay; p24 antigen ELISA for viral replication Journal of immunology Medium 7594489
2002 CR1 (CD35) on B lymphocytes mediates inhibitory signals: clustering of CR1 with multimeric C3b-like ligands inhibits anti-IgM-induced B cell proliferation, reduces intracellular Ca2+ transients, and reduces phosphorylation of cytoplasmic proteins. This inhibitory effect persists in the presence of IL-2 and IL-15. Aggregated C3/C3(H2O) stimulation of tonsil B cells; 3H-thymidine proliferation assay; intracellular Ca2+ fluorometry; phosphoprotein analysis Journal of immunology Medium 11884446
2006 CR1 triggering on human T lymphocytes and T cell lines with anti-CR1 antibodies inhibits proliferation and blocks cytokine protein synthesis (IFN-γ, IL-2) and expression of cyclins A and D3 and PCNA, without affecting immediate-early gene transcription (c-jun, c-fos) or early cytokine mRNA levels. The inhibitory mechanism acts downstream of initial signaling events. Anti-CR1 antibody stimulation of peripheral T cells and T cell lines; 3H-thymidine proliferation assay; RT-PCR for early gene transcripts; protein expression by Western blot/ELISA Molecular immunology Medium 16360013
1994 An acidic cluster near the N-terminus of the C3b α'-chain (residues 730–739, particularly Glu-736 and Glu-737) is required for C3b interaction with factor B and with CR1 (CR1-dependent factor I cofactor activity). A distinct region (Glu-744, Glu-747) overlaps with factor H but not CR1 binding. MCP binding sites on C3b/C3(H2O) are entirely distinct from those of H and CR1. Site-directed mutagenesis of C3 residues; factor I cofactor cleavage assay as surrogate binding assay for CR1, factor H, and MCP interactions Journal of immunology Medium 7963581
1999 Acidic residues in C3b α'-chain segment 738–767 (Glu-744, Glu-747, Glu-754/Asp-755, Lys-757/Glu-758) are required for CR1-dependent factor I cofactor activity. CR1 contacts extend over a wider portion of the 727–767 segment than factor H contacts, and CR1 requires basic residues to form the interface with this acidic region of C3b. Charged-residue mutagenic scan of C3 residues 738–767; factor I cofactor cleavage assay for soluble CR1, factor H, and MCP The Journal of biological chemistry Medium 9988761
2005 CR1 has two distinct functional sites (Site 1: CCPs 1–3; Site 2: CCPs 8–10 and 15–17). For the classical pathway C5 convertase, Site 1 mediates dissociation while Site 2 binds the C3b subunit; intervening CCPs are required for proper spatial orientation. Two copies of Site 1 in tandem show up to 58-fold synergistic increase in decay-accelerating activity (DAA) for the C3 convertase, suggesting a dimeric structure for the classical pathway C3 convertase on cell surfaces. Phe82 and the CCP1/CCP2 junction are critical for DAA. Mutagenesis and expression of CR1 site constructs; decay-accelerating activity assays for C3 and C5 convertases; generation of tandem site constructs Journal of immunology Medium 16177096
1994 Soluble CR1 (sCR1) in plasma is generated by proteolytic cleavage of cell-surface CR1. PMN-derived sCR1 lacks the intracellular domain (detected by C-terminal peptide ELISA). PMN release sCR1 at highest levels among leukocytes; fMLP, TNF-α, and LPS accelerate release; GM-CSF sustains CR1 gene expression and total sCR1 release. Intracellular-domain-specific ELISA; in vitro stimulation of PMN and cell lines; sCR1 size comparison by SDS-PAGE; RT-PCR for CR1 mRNA European journal of immunology Medium 7957565
1994 CR1 on human glomerular podocytes is released as membrane-bound vesicles into urine. Urinary CR1 (uCR1) is membrane-associated (pelleted at 200,000g), enriched in cholesterol and phospholipids, and visualized as membrane vesicles by electron microscopy. Renal transplant allele discordance confirms kidney (podocyte) origin. uCR1 retains C3b-binding function. Ultracentrifugation; sucrose density gradient; cholesterol/phospholipid measurement; immunoaffinity purification and electron microscopy; SDS-PAGE; renal transplant allele analysis; C3b-binding functional assay The Journal of experimental medicine High 8113681
1999 Hypoxia induces functional CR1 expression on human vascular endothelial cells (HUVECs). CR1 protein increases ~3.7-fold after 48h at 1% O2; CR1 is predominantly intracellular by confocal microscopy. Hypoxic HUVECs bind immune complexes and act as cofactor for factor I-mediated C3b cleavage. LPS and TNF-α also increase HUVEC CR1 expression. ELISA; confocal colocalization with von Willebrand factor; Western blot; RT-PCR and in situ hybridization; immune complex binding assay; factor I cofactor activity assay The American journal of physiology Medium 9950773
1992 CR1 functions as cofactor for factor I-mediated cleavage of both fluid-phase and liposome-bound C4b. CR1 generates primarily C4bi from fluid-phase C4b but C4c/C4d from liposome-bound C4b. CR1 has dual optimal pH (6.0 and 7.5 for fluid phase; 6.0 for solid phase) and is a more potent cofactor for C4b cleavage than for C3b cleavage. MCP acts more efficiently on C3b than C4b. In vitro cofactor cleavage assay with purified components; SDS-PAGE analysis of cleavage products; pH titration; detergent concentration variation Journal of biochemistry Medium 1386357
1991 Phagocytosis of Mycobacterium leprae by human monocyte-derived macrophages (MDM) is mediated by CR1, CR3, and CR4 together; combined blockade of all three receptors reduces adherence by 80%. IFN-γ activation reduces M. leprae phagocytosis by markedly decreasing surface expression of CR1 (by up to 75%), providing a molecular mechanism for IFN-γ-mediated inhibition of complement-dependent phagocytosis. Monoclonal antibody blocking of individual and combined complement receptors; light and electron microscopy for adherence/ingestion quantification; flow cytometry for CR1 surface expression after IFN-γ treatment Journal of immunology Medium 1679838
1993 CR1 and CR3 mediate productive infection of human monocytes and monocytic cell lines with complement-opsonized HIV-1 and HIV-2 independently of CD4. Blocking CR1 or CR3 with F(ab')2 antibodies abolishes the complement-enhancement of infection. Infection occurs in CD4-negative cell lines (Mono Mac 6, U251-MG) and is not blocked by anti-CD4 antibody. F(ab')2 antibody blockade of CR1 and CR3; viral infection with complement-opsonized HIV; p24 antigen ELISA; syncytia formation; MTT cytotoxicity; CD4-negative cell line controls Clinical and experimental immunology Medium 7682158
1996 The recombinant soluble form of CR1 (rsCD35) is a more effective inhibitor of classical pathway complement activation in vitro than rsCD46 or rsCD55 alone. rsCD35 and rsCD46 regulate alternative pathway cell lysis to a similar extent, whereas rsCD55 is ineffective against the alternative pathway. In vitro complement activation assays (classical and alternative pathways); cell lysis assays with purified recombinant proteins European journal of immunology Medium 8605924
1994 Two amino acid substitutions (Tyr for Ser37 and Asp for Gly79) at homologous positions in CCP1 and CCP2 of the CR1 C4b-binding site confer C3b binding while retaining C4b binding. Single substitutions are insufficient; the double substitution mimics the C3b-binding site of human CR1. Site-directed mutagenesis of truncated CR1 constructs; rosette formation with C3b- and C4b-coated erythrocytes; factor I cofactor activity assay Journal of immunology (via PMID:8757632, published 1996) Medium 8757632
1994 Murine CR1 (the 6 SCRs appended to mouse CR2) binds both C3b and C4b through a single site requiring SCR-1 as an absolute requirement; deletion of SCRs 5–6 reduces but does not abolish binding of both ligands; constructs lacking SCR-1 (e.g., SCRs 2–6, 2–5, 3–6) lack activity entirely. Murine CR1/human CR2 chimeric constructs expressed in K562 cells; rosette formation assay with C3b- and C4b-coated erythrocytes Journal of immunology Medium 8144890
2018 Both C1q and MBL bind CR1 at the same pair of CCP24–25 modules within LHR-D. A CR1 fragment lacking CCP24–25 loses both C1q and MBL binding. C1q binding involves the collagen stalks as a main site plus subsidiary sites on globular heads, contrasting with MBL which uses only the collagen stalks. CR1 deletion variants (CCP24-25 isolated fragment; CCP22-30 lacking CCP24-25) produced in eukaryotic cells; C1q and MBL binding assays; competitive binding experiments Frontiers in immunology Medium 29563915
2015 CR1 on epithelial cells (podocyte model using CHO cells) reduces C3b deposition by ~80% during classical pathway activation and >95% during alternative pathway activation, primarily via decay-accelerating activity. Deposited C4b/C3b are progressively cleaved with t½ ~30 min by CR1 cofactor activity. CR1 functions intrinsically (only on the cell it is expressed on) and stably binds but does not internalize C4b/C3b-opsonized immune complexes. CHO cell expression system; C3b deposition assay (classical and alternative pathways); cofactor cleavage kinetics; internalization assay Molecular immunology Medium 26260209
2015 Co-ligation of CR1 (CD35) and CD46 on activated CD4+ T cells synergistically enhances CD25 expression, granzyme B production, IL-10 secretion, and reduces IFN-γ release, promoting development of a regulatory T cell phenotype. CR1/CD46 double-positive T cells are found in inter-follicular regions of tonsils in vivo. Anti-CR1 and anti-CD46 antibody co-ligation; ELISA for cytokines; flow cytometry for CD25 and granzyme B; immunohistochemical staining of tonsil sections Immunology letters Medium 25742728
1986 Human glomerular podocytes express CR1 as the sole C3 receptor type. Glomerular CR1 binds C3b-coated erythrocytes (not C3dg, C3d, or C3bi), shares functional and antigenic properties with peripheral blood CR1, and has decay-accelerating activity for the C3 convertase. Anti-CR1 F(ab')2 specifically inhibits binding, and immunoprecipitation of surface-labeled glomerular proteins yields CR1 of Mr 205,000. Rosette adherence assay with defined C3-fragment-coated erythrocytes; indirect immunofluorescence with anti-CR1, anti-CR2, anti-CR3 antibodies; complement convertase decay assay; 125I surface labeling and immunoprecipitation/SDS-PAGE Journal of immunology High 2418113

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
1988 Identification of distinct C3b and C4b recognition sites in the human C3b/C4b receptor (CR1, CD35) by deletion mutagenesis. The Journal of experimental medicine 251 2972794
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
1991 Phagocytosis of Mycobacterium leprae by human monocyte-derived macrophages is mediated by complement receptors CR1 (CD35), CR3 (CD11b/CD18), and CR4 (CD11c/CD18) and IFN-gamma activation inhibits complement receptor function and phagocytosis of this bacterium. Journal of immunology (Baltimore, Md. : 1950) 144 1679838
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) 121 8326130
2013 Human complement receptor type 1/CD35 is an Epstein-Barr Virus receptor. Cell reports 109 23416052
1997 Mouse complement receptors type 1 (CR1;CD35) and type 2 (CR2;CD21): expression on normal B cell subpopulations and decreased levels during the development of autoimmunity in MRL/lpr mice. Journal of immunology (Baltimore, Md. : 1950) 106 9233655
2011 Complement receptor 1 (CR1) and Alzheimer's disease. Immunobiology 96 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
2001 CR1 and CR1-like: the primate immune adherence receptors. Immunological reviews 85 11414352
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
2009 Expression and role of CR1 and CR2 on B and T lymphocytes under physiological and autoimmune conditions. Molecular immunology 68 19559484
2008 Comparative functional evolution of human and mouse CR1 and CR2. Journal of immunology (Baltimore, Md. : 1950) 68 18713965
1993 CR1 (CD35) and CR3 (CD11b/CD18) mediate infection of human monocytes and monocytic cell lines with complement-opsonized HIV independently of CD4. Clinical and experimental immunology 66 7682158
2012 Genetic association of CR1 with Alzheimer's disease: a tentative disease mechanism. Neurobiology of aging 63 22819390
1995 Triggering of complement receptors CR1 (CD35) and CR3 (CD11b/CD18) induces nuclear translocation of NF-kappa B (p50/p65) in human monocytes and enhances viral replication in HIV-infected monocytic cells. Journal of immunology (Baltimore, Md. : 1950) 63 7594489
2009 The structure, genetic polymorphisms, expression and biological functions of complement receptor type 1 (CR1/CD35). Immunopharmacology and immunotoxicology 60 19874218
2000 Activation of knot (kn) specifies the 3-4 intervein region in the Drosophila wing. Development (Cambridge, England) 60 10654600
2017 Neonatal and adult recent thymic emigrants produce IL-8 and express complement receptors CR1 and CR2. JCI insight 55 28814669
1994 Interactions of human complement component C3 with factor B and with complement receptors type 1 (CR1, CD35) and type 3 (CR3, CD11b/CD18) involve an acidic sequence at the N-terminus of C3 alpha'-chain. Journal of immunology (Baltimore, Md. : 1950) 54 7963581
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
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
2006 The complement receptor 1, CR1 (CD35), mediates inhibitory signals in human T-lymphocytes. Molecular immunology 47 16360013
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
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
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 44 8605924
1994 Soluble complement receptor type 1 (CD35) is released from leukocytes by surface cleavage. European journal of immunology 43 7957565
1999 Identification of residues within the 727-767 segment of human complement component C3 important for its interaction with factor H and with complement receptor 1 (CR1, CD35). The Journal of biological chemistry 41 9988761
2022 Age is no barrier for adults undergoing HCT for AML in CR1: contemporary CIBMTR analysis. Bone marrow transplantation 39 35368040
2012 Complement receptor type 1 (CR1, CD35) is a potent inhibitor of B-cell functions in rheumatoid arthritis patients. International immunology 39 22962438
1990 Expression of CR1 (CD35) mRNA in podocytes from adult and fetal human kidneys. Kidney international 39 2402120
1991 Differential effects of the stimulation of complement receptors CR1 (CD35) and CR2 (CD21) on cell proliferation and intracellular Ca2+ mobilization of chronic lymphocytic leukemia B cells. Journal of immunology (Baltimore, Md. : 1950) 38 1826011
2015 KN-93 inhibits IKr in mammalian cardiomyocytes. Journal of molecular and cellular cardiology 36 26463508
1994 CR1(CD35) and CR2(CD21) complement C3 receptors are expressed on normal human thymocytes and mediate infection of thymocytes with opsonized human immunodeficiency virus. European journal of immunology 36 7957570
1999 Hypoxia-induced expression of complement receptor type 1 (CR1, CD35) in human vascular endothelial cells. The American journal of physiology 35 9950773
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
1991 Genomic determination of the CR1 (CD35) density polymorphism on erythrocytes using polymerase chain reaction amplification and HindIII restriction enzyme digestion. Journal of immunological methods 34 1671871
2018 Complement receptor 1 gene (CR1) intragenic duplication and risk of Alzheimer's disease. Human genetics 33 29675612
2012 Implication of common and disease specific variants in CLU, CR1, and PICALM. Neurobiology of aging 33 22402018
1999 Complement receptor 1 (CD35) on human reticulocytes: normal expression in systemic lupus erythematosus and HIV-infected patients. Journal of immunology (Baltimore, Md. : 1950) 33 10358211
1994 Binding of human immunodeficiency virus type 1 to the C3b/C4b receptor CR1 (CD35) and red blood cells in the presence of envelope-specific antibodies and complement. National Institutes of Health AIDS Vaccine Clinical Trials Networks. The Journal of infectious diseases 33 8035031
1992 Expression, molecular association, and functions of C3 complement receptors CR1 (CD35) and CR2 (CD21) on the human T cell line HPB-ALL. Journal of immunology (Baltimore, Md. : 1950) 32 1386093
1992 Factor I-dependent inactivation of human complement C4b of the classical pathway by C3b/C4b receptor (CR1, CD35) and membrane cofactor protein (MCP, CD46). Journal of biochemistry 32 1386357
1993 Expression of CD35 (CR1) and CD11b (CR3) on circulating neutrophils and eosinophils from allergic asthmatic children. Clinical and experimental allergy : journal of the British Society for Allergy and Clinical Immunology 30 10779280
1992 Peripheral catabolism of CR1 (the C3b receptor, CD35) on erythrocytes from healthy individuals and patients with systemic lupus erythematosus (SLE). Clinical and experimental immunology 30 1531948
1991 Flow cytometric assay for phagocytosis of human monocytes mediated via Fc gamma-receptors and complement receptor CR1 (CD35). Cytometry 30 1838328
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
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
2017 The Multifaceted Personality of Intestinal CX3CR1+ Macrophages. Trends in immunology 27 28844811
2002 Human umbilical vein endothelial cells express complement receptor 1 (CD35) and complement receptor 4 (CD11c/CD18) in vitro. Inflammation 27 12083416
1986 Defective complement receptors (CR1 and CR3) on erythrocytes and leukocytes of factor I (C3b-inactivator) deficient patients. Clinical and experimental immunology 27 2949901
2006 Consumption of erythrocyte CR1 (CD35) is associated with protection against systemic lupus erythematosus renal flare. Clinical and experimental immunology 26 16412051
2003 Regulation of B-cell activation by complement receptors CD21 and CD35. Current pharmaceutical design 26 12871189
2000 Immunomodulatory functions of murine CR1/2. Immunopharmacology 26 10904111
1989 Genetic analysis of CR1 (the C3b complement receptor, CD35) expression on erythrocytes of HIV-infected individuals. AIDS (London, England) 26 2568845
2011 CLU, CR1 and PICALM genes associate with Alzheimer's-related senile plaques. Alzheimer's research & therapy 25 21466683
2006 Quantitative analysis of complement receptors, CR1 (CD35) and CR3 (CD11b), on neutrophils improves distinction between bacterial and viral infections in febrile patients: comparison with standard clinical laboratory data. Journal of immunological methods 25 16970963
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
2000 Regulation of humoral immune responses by CD21/CD35. Immunological reviews 24 11043778
2021 Acquired decrease of the C3b/C4b receptor (CR1, CD35) and increased C4d deposits on erythrocytes from ICU COVID-19 patients. Immunobiology 23 34022670
1997 CR1, CD35 in synovial fluid from patients with inflammatory joint diseases. Arthritis and rheumatism 23 9082940
1994 Binding of C3b and C4b by the CR1-like site in murine CR1. Journal of immunology (Baltimore, Md. : 1950) 23 8144890
2015 Production of ginsenoside F1 using commercial enzyme Cellulase KN. Journal of ginseng research 22 27158232
2005 Synergy between two active sites of human complement receptor type 1 (CD35) in complement regulation: implications for the structure of the classical pathway C3 convertase and generation of more potent inhibitors. Journal of immunology (Baltimore, Md. : 1950) 22 16177096
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
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
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
2005 Acquired but reversible loss of erythrocyte complement receptor 1 (CR1, CD35) and its longitudinal alteration in patients with severe acute respiratory syndrome. Clinical and experimental immunology 20 15606620
1996 Reduction in erythrocyte complement receptor 1 (CR1, CD35) and decay accelerating factor (DAF, CD55) during normal pregnancy. Journal of reproductive immunology 19 8905554
1987 C3b receptor (CR1) expression on the polymorphonuclear leukocytes from patients with systemic lupus erythematosus. Clinical and experimental immunology 19 2955969
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
1987 Erythrocyte complement receptor type 1 (CR1) expression and circulating immune complex (CIC) levels in hydralazine-induced SLE. Clinical and experimental immunology 18 2958187
2011 The E3 CR1-gamma gene in human adenoviruses associated with epidemic keratoconjunctivitis. Virus research 17 21683743
2010 KN-93 inhibits androgen receptor activity and induces cell death irrespective of p53 and Akt status in prostate cancer. Cancer biology & therapy 17 20023417
2007 Resistance to Fas-mediated apoptosis in malignant tumours is rescued by KN-93 and cisplatin via downregulation of c-FLIP expression and phosphorylation. Clinical and experimental pharmacology & physiology 17 17973862
1997 Catabolism of the human erythrocyte C3b/C4b receptor (CR1, CD35): vesiculation and/or proteolysis? Immunopharmacology 17 9476124
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
1992 Levels of complement receptor type one (CR1, CD35) on erythrocytes, circulating immune complexes and complement C3 split products C3d and C3c are not changed by short-term physical exercise or training. International journal of sports medicine 17 1555909

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