Affinage

C4BPB

C4b-binding protein beta chain · UniProt P20851

Length
252 aa
Mass
28.4 kDa
Annotated
2026-04-28
78 papers in source corpus 26 papers cited in narrative 24 extracted findings

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

C4BPB encodes the beta-chain of C4b-binding protein (C4BP), a major soluble inhibitor of the classical and lectin complement pathways whose alpha-chains bind C4b through a positively charged cluster at the CCP1–CCP2 interface and serve as cofactor for factor I–mediated cleavage of C4b and C3b (PMID:10383431, PMID:11369776, PMID:12893820). The beta-chain's SCR1–SCR2 domains constitute the high-affinity protein S binding site; this interaction competitively abolishes protein S cofactor function for TFPI without affecting its activated protein C cofactor activity, thereby linking complement regulation to coagulation control (PMID:10329721, PMID:34731882). Plasma C4BP isoform composition (alpha7-beta1, alpha7-beta0, alpha6-beta1) is genetically determined by relative C4BPA and C4BPB expression levels, and differential cytokine regulation—IL-6 selectively upregulates C4BPB via STAT3 while TNF-α/IFN-γ combinations preferentially induce C4BPA—shifts the balance toward beta-chain-lacking isoforms during acute-phase responses, augmenting a non-canonical immunomodulatory activity of the alpha-chain CCP6 domain that reprograms inflammatory myeloid cells (PMID:7561114, PMID:18752574, PMID:31982108). Multiple streptococcal M-protein hypervariable regions recruit C4BP to the bacterial surface via the alpha-chain CCP1–3 C4b-binding site, enabling phagocytosis resistance through molecular mimicry (PMID:8943398, PMID:11703674, PMID:38879009).

Mechanistic history

Synthesis pass · year-by-year structured walk · 13 steps
  1. 1983 Medium

    Early proteolytic mapping established that C4BP harbors separable functional domains: an N-terminal region mediating C4b binding and a core/C-terminal domain binding protein S, setting the stage for chain-specific functional dissection.

    Evidence Chymotryptic fragmentation of purified C4BP with binding assays for C4b and protein S

    PMID:6653778

    Open questions at the time
    • No chain-level resolution (alpha vs. beta not distinguished)
    • No domain boundaries defined at the SCR/CCP level
  2. 1995 Medium

    Demonstration that C4BP exists as multiple isoforms (alpha7-beta1, alpha7-beta0, alpha6-beta1) whose stoichiometry is genetically set by relative C4BPA/C4BPB expression resolved a long-standing question of why free protein S varies among individuals; it also showed cytokine-driven differential regulation (TNF-α/IFN-γ synergy on C4BPA >> C4BPB) provides a mechanism to shift isoform composition during inflammation.

    Evidence HepG2/Hep3B secretion studies, COS transfection, Northern blots with cytokine treatments in Hep3B cells, acute-phase patient plasma analysis

    PMID:7561113 PMID:7561114

    Open questions at the time
    • Promoter elements driving differential regulation only partially mapped
    • In vivo human time-course data lacking
  3. 1996 Medium

    Identification of the C4BPB promoter region (-126 to +25) driven by cooperative HNF-3 and NF-I/CTF binding explained hepatocyte-specific expression and provided a framework for understanding how cytokine signaling differentially controls C4BPB transcription.

    Evidence Reporter gene assays with promoter deletions in HepG2; EMSA identifying transcription factor binding sites

    PMID:8598458

    Open questions at the time
    • Cytokine-responsive elements not mapped within this promoter
    • In vivo chromatin accessibility not examined
  4. 1994 High

    Discovery that the murine C4BPB gene is a pseudogene with in-phase stop codons established that the protein S–C4BP regulatory axis is absent in mice, a critical caveat for interpreting mouse models of complement and coagulation.

    Evidence Genomic sequencing of C4BPB across multiple mouse strains; Southern blotting and chromosomal mapping

    PMID:7959726

    Open questions at the time
    • Functional consequences of absent beta-chain for mouse protein S regulation not fully characterized
  5. 1999 High

    Mapping the C4b-binding site to a positively charged cluster (R39, R64, R66) at the CCP1–CCP2 junction of the alpha-chain, and identifying beta-chain SCR1–SCR2 as the protein S binding site, achieved residue-level functional assignment for both chains of C4BP.

    Evidence Site-directed mutagenesis with SPR binding and factor I cofactor assays (alpha-chain); chimeric SCR constructs with protein S binding and APC cofactor assays (beta-chain)

    PMID:10329721 PMID:10383431 PMID:10744423

    Open questions at the time
    • Structural basis of SCR1–SCR2/protein S interface not resolved at atomic level
    • No crystal structure of beta-chain domains available
  6. 2001 High

    Systematic CCP-deletion analysis of the alpha-chain defined the minimal domain requirements: CCP1–3 for C4b cofactor activity (CCP2–3 indispensable), CCP1–5 for C3b cofactor activity, with polymerization enhancing surface-bound C4b degradation efficiency.

    Evidence 19 recombinant C4BP variants including truncations and deletions tested for C4b/C3b binding, cofactor, and convertase inhibition

    PMID:11369776 PMID:12417021

    Open questions at the time
    • Mechanism by which polymerization enhances activity (avidity vs. conformational) not resolved
  7. 2003 High

    Identification of a cofactor-specific surface on CCP3 (K126/K128, F144/F149) that is essential for factor I–mediated cleavage but dispensable for C4b binding or convertase decay separated binding from catalytic cofactor function, demonstrating that C4BP employs distinct surfaces for substrate capture versus protease activation.

    Evidence Site-directed mutagenesis with SPR, cofactor, and convertase assembly/decay assays

    PMID:12893820

    Open questions at the time
    • Structural mechanism of factor I activation by CCP3 residues unknown
    • No ternary C4BP–C4b–factor I complex structure
  8. 2003 High

    Discovery that the C4BP alpha-chain binds CD40 on B cells at a site distinct from CD40L, triggering proliferation, co-stimulatory molecule upregulation, and IL-4-dependent IgE switching, revealed an unexpected immune-regulatory function beyond complement control.

    Evidence Direct binding assays, B cell proliferation and isotype switching assays, CD40-deficient and IKKγ-deficient patient B cells, germinal center colocalization

    PMID:12818164

    Open questions at the time
    • Alpha-chain domain mediating CD40 binding not mapped
    • Physiological significance in vivo not established
  9. 2006 High

    SPR analysis of C4c and C4dg subfragments revealed that C4BP binds C4b through synergistic subsites within CCP1–3, where occupancy of one subsite shifts a conformational equilibrium to enhance affinity at the other, explaining the high cooperativity of C4b recognition.

    Evidence SPR with C4b subfragments, C4BP mutants, and cross-competition experiments

    PMID:16819837

    Open questions at the time
    • Atomic-level structural basis of conformational shift not determined
  10. 2008 Medium

    In vivo demonstration that IL-6 upregulates C4BPB specifically through STAT3, while LPS downregulates both chains via NF-κB/MEK-ERK, provided a signaling-level mechanism for how inflammation shifts C4BP isoforms to increase protein S sequestration and reduce anticoagulant activity.

    Evidence Rat LPS/IL-6 injection, isolated hepatocyte treatment, pathway inhibitor experiments

    PMID:18752574

    Open questions at the time
    • Direct STAT3 binding to C4BPB promoter not shown
    • Translation to human hepatocytes not confirmed
  11. 2019 Medium

    The beta-chain-lacking C4BP(β−) isoform was shown to reprogram inflammatory myeloid cells to an anti-inflammatory/tolerogenic state via the alpha-chain CCP6 domain, while incorporation of the beta-chain suppresses this activity, establishing the beta-chain as a negative modulator of C4BP's non-canonical immunomodulatory function.

    Evidence Lupus-prone mouse model, monocyte-derived DC reprogramming, domain-deletion constructs, cytokine and transcriptional profiling

    PMID:31982108 PMID:35547734

    Open questions at the time
    • Receptor for CCP6-mediated myeloid reprogramming unidentified
    • Mechanism by which beta-chain interferes with CCP6 activity unclear
    • Human in vivo relevance not demonstrated
  12. 2022 High

    Residue-level mapping showed that C4BP beta-chain binding to protein S LG1 domain abolishes TFPI cofactor function while preserving APC cofactor function, resolving a longstanding question of how protein S simultaneously participates in anticoagulant and complement pathways and establishing competitive regulation at a shared surface.

    Evidence Glycosylation insertion scanning, alanine mutagenesis of protein S LG1, FXa inhibition assays, plasma TFPI cofactor assays

    PMID:34731882

    Open questions at the time
    • Structural model of beta-chain SCR1–2/protein S LG1 complex lacking
    • In vivo consequences of selective TFPI pathway inhibition not tested
  13. 2024 High

    Crystal structures of streptococcal M-protein HVRs in complex with C4BP alpha-chain fragments revealed multiple distinct C4BP-binding sequence patterns beyond previously known types, showing that pathogen exploitation of the C4b-binding site has diversified through convergent evolution including in M-like Enn proteins.

    Evidence X-ray crystallography, site-directed mutagenesis of M proteins and Enn proteins, C4BP binding assays

    PMID:38879009

    Open questions at the time
    • Full-length C4BP–M protein complex structure not available
    • Functional impact on complement evasion in animal infection models not tested with these specific patterns

Open questions

Synthesis pass · forward-looking unresolved questions
  • Key unresolved questions include: the atomic structure of the beta-chain SCR1–2/protein S complex, the receptor through which the C4BP(β−) CCP6 domain reprograms myeloid cells, the structural mechanism by which beta-chain incorporation suppresses immunomodulatory activity, and whether isoform-specific C4BP functions are druggable targets in thromboinflammatory disease.
  • No crystal/cryo-EM structure of beta-chain or its complex with protein S
  • CCP6 myeloid receptor unidentified
  • No therapeutic modulation studies targeting isoform balance

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0098772 molecular function regulator activity 9 GO:0060090 molecular adaptor activity 3
Localization
GO:0005576 extracellular region 3
Pathway
R-HSA-168256 Immune System 9 R-HSA-109582 Hemostasis 3
Partners
C3C4BC4BPACD40CFIPROS1
Complex memberships
C4b-binding protein (C4BP)

Evidence

Reading pass · 24 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2003 The alpha-chain of human C4BP binds directly to CD40 on human B cells at a site distinct from that used by CD40 ligand, inducing B cell proliferation, upregulation of CD54 and CD86, and IL4-dependent IgE isotype switching. This effect requires CD40 and IKKgamma/NEMO signaling. Direct binding assay, B cell proliferation assay, isotype switching assay, use of B cells from CD40/IKKgamma-deficient patients, colocalization in germinal centers Immunity High 12818164
2001 The N-terminal CCP domains 1–3 of the C4BP alpha-chain are required for C4b binding and complement regulatory activity; CCP2 and CCP3 are most critical. Polymeric C4BP is more efficient than monomeric forms at degrading surface-bound C4b. Spatial arrangements between CCPs are important for full function. Expression of 19 recombinant C4BP variants (truncated, polymeric with CCP deletions, alanine-insertion mutants); functional assays for C4b binding, factor I cofactor activity, C3-convertase inhibition The Journal of biological chemistry High 11369776
1999 A cluster of positively charged amino acids (R39, R64, R66) at the interface between CCP1 and CCP2 of the C4BP alpha-chain constitutes the C4b-binding site and a specific heparin-binding site. These residues are required for factor I cofactor function and cleavage of specific peptide bonds in C4b. Site-directed mutagenesis (R39Q, R64Q/R66Q, R39Q/R64Q/R66Q), surface plasmon resonance-based binding assays, factor I cofactor degradation assays, heparin binding assays The Journal of biological chemistry High 10383431
2003 Mutations K126Q/K128Q and F144S/F149S in CCP3 of the C4BP alpha-chain selectively abolish factor I cofactor activity for C4b and C3b cleavage without affecting C4b/C3b binding affinity or inhibition of C3-convertase assembly/decay, indicating CCP3 contains a surface required for cofactor activity distinct from the binding site. Site-directed mutagenesis, surface plasmon resonance binding assays, fluid-phase cofactor assays, C3-convertase assembly/decay assays The Journal of biological chemistry High 12893820
2000 Positively charged residues R39, K63, R64, and H67 at the CCP1-CCP2 interface of C4BP alpha-chain are required for C3-convertase regulation (inhibiting assembly and accelerating decay) and factor I cofactor activity in fluid-phase C4b degradation. Expression of nine C4BP mutants with positively charged amino acids replaced by glutamine; C3-convertase assembly/decay assays, factor I cofactor assays Molecular immunology High 11090879
2002 Deletion mutagenesis of C4BP alpha-chain SCR domains showed SCR2 and SCR3 are indispensable for C4b cleavage cofactor activity (SCR1 contributes additionally), while SCR1-5 participate in C3b cofactor activity with SCR2, 3, 4 being absolutely required. C4b and C3b binding domains partially differ from domains mediating cofactor activity. SCR-deletion mutants of recombinant multimeric C4BP; C3b/C4b-Sepharose binding, ELISA binding, fluid-phase cofactor assays Journal of biochemistry High 12417021
2009 C4BP regulates the lectin pathway C3/C5 convertase; at high C4b density on activating surfaces, all seven alpha-chains engage C4b simultaneously. C4BP has approximately 7–13-fold greater affinity for C4b deposited via the lectin pathway than via the classical pathway, providing stringent regulation of the lectin pathway. Binding assays on zymosan and mannan-coated erythrocytes; C3/C5 convertase assembly inhibition assays; quantitative C4b per C4BP analysis Molecular immunology Medium 19660812
2006 C4BP interacts with both C4c and C4dg subfragments of C4b via adjacent but distinct subsites within CCP1–3 of the alpha-chain; filling the C4dg subsite enhances C4c binding (and vice versa) by shifting a conformational equilibrium toward a high-affinity state, indicating synergy between C4b subsites. Surface plasmon resonance with C4c and C4dg subfragments; C4b-binding-defective C4BP mutants; cross-competition experiments Biochemistry High 16819837
1999 The protein S binding site on C4BP is located in the beta-chain; SCR-1 is the primary binding domain and SCR-2 specifically contributes to the interaction, increasing affinity up to 5-fold over SCR-1 alone. Binding to SCR-1-containing constructs decreases protein S cofactor activity for activated protein C. Chimeric constructs of C4BP beta-chain SCRs fused to tissue-type plasminogen activator; protein S binding assays; protein S cofactor activity assays The Journal of biological chemistry High 10329721 10744423
1997 A region of protein S around residues 447–460 (within the LG-type domain) constitutes a portion of the protein S binding site for C4BP; synthetic peptides spanning this region inhibit protein S–C4BP interaction and directly bind C4BP. Bacteriophage peptide display library selection against C4BP beta-chain; synthetic peptide inhibition assays; CD spectroscopy and tryptophan fluorescence polarization binding assays The Journal of biological chemistry Medium 9169428
2022 Protein S residues Lys255, Glu257, Asp287, Arg410, Lys423, and Glu424 in the LG1 domain are critical for TFPI cofactor function. C4BP beta-chain binding to protein S LG1 almost completely abolishes this TFPI cofactor function while leaving activated protein C cofactor function intact, demonstrating competitive regulation at a shared LG1 surface. N-linked glycosylation insertion scanning of protein S LG1; alanine substitution variants; FXa inhibition assays; plasma TFPI cofactor assays; C4BP beta-chain expression and binding Blood advances High 34731882
1995 Human C4BP exists as multiple plasma isoforms (alpha7beta1, alpha7beta0, alpha6beta1) whose proportions are genetically determined by the relative expression levels of the C4BPA and C4BPB genes. The beta-chain (encoded by C4BPB) binds protein S, while the alpha-chain mediates complement regulation. Biochemical characterization of HepG2 and Hep3B cell secretion; COS cell transfection experiments; gel electrophoresis and immunoassay quantification of isoforms Journal of immunology Medium 7561113
1995 IL-6, IL-1β, and IFN-γ increase both C4BPA and C4BPB mRNA levels, while TNF-α downregulates both. IFN-γ shows a differential effect, and when combined with TNF-α produces synergistic 10-fold induction of C4BPA mRNA but only marginal increase of C4BPB mRNA, providing a mechanism to maintain C4BP beta concentrations during acute phase response. Hep3B cell treatment with cytokines; Northern blot mRNA quantification of C4BPA and C4BPB; acute phase patient plasma C4BP isoform analysis Journal of immunology Medium 7561114
1996 The C4BPB gene promoter region from -126 to +25 drives hepatocyte expression; a critical subfragment (-126 to -90) provides >90% of promoter activity through cooperative binding of HNF-3 and NF-I/CTF transcription factors. Reporter gene assays in HepG2 cells with promoter deletion constructs; electrophoretic mobility shift assays identifying HNF-3 and NF-I/CTF binding Journal of immunology Medium 8598458
1994 The murine C4BPB gene is a single-copy pseudogene containing two in-phase stop codons in its CCP-encoding exons, incompatible with a functional C4BP beta polypeptide. This demonstrates that the mouse lacks a functional beta-chain and thus cannot form the protein S-binding C4BP isoform. Genomic DNA isolation and sequencing from multiple mouse strains; Southern blotting; chromosomal mapping showing close linkage to C4BPA on mouse chromosome 1 Genomics High 7959726
2008 LPS decreases both C4BPalpha and C4BPbeta expression in rat hepatocytes via NFkappaB and MEK/ERK pathways, while IL-6 specifically increases C4BPbeta expression via STAT-3, leading to increased plasma PS-C4BP complex and decreased protein S anticoagulant activity. In vivo rat LPS/IL-6 injection; isolated rat hepatocyte treatment; mRNA and protein quantification; pathway inhibitor experiments (NFkappaB, MEK/ERK, STAT-3 inhibitors) Journal of thrombosis and haemostasis Medium 18752574
1983 Chymotryptic cleavage of C4BP yields a 48 kDa N-terminal fragment and a 27 kDa C-terminal fragment joined by disulfide bonds; the 48 kDa fragment released from the N-terminal side retains C4b-binding activity, while the protein S binding site was localized to the core (C-terminal) domain. Chymotrypsin proteolysis; N-terminal amino acid sequencing; C4b and protein S binding assays of fragments FEBS letters Medium 6653778
2003 Protein S and the C4BP-protein S complex bind to apoptotic neutrophils (and Jurkat cells) through the Gla domain of protein S interacting with negatively charged phospholipids exposed on apoptotic cells; only the apoptotic neutrophil subpopulation binds these proteins. Flow cytometry-based binding assays; blocking with anti-Gla domain monoclonal antibody; comparison of apoptotic vs. non-apoptotic neutrophil populations Blood coagulation & fibrinolysis Medium 12945877
2008 Human C4BP injected intraperitoneally inhibits complement-mediated arthritis in mouse models (CAIA and CIA), with C4BP inhibiting the classical but also the alternative pathway when present on activating surfaces, ameliorating disease severity without affecting anti-CII antibody synthesis. Mouse collagen antibody-induced arthritis (CAIA) and collagen-induced arthritis (CIA) models; intraperitoneal injection of purified human C4BP; classical and alternative pathway activity assays; anti-CII antibody measurement Annals of the rheumatic diseases Medium 18276745
2006 The hypervariable region (HVR) of streptococcal M proteins folds as a coiled-coil and binds C4BP via a surface spanning four heptad repeats in approximately the N-terminal 27-residue folded nucleus of M4 HVR; the C4BP binding surface of M4 is distinct from the folded coiled-coil core. NMR spectroscopy of M4 and M22 HVRs free and in complex with C4BP fragment; molecular modeling Biochemistry Medium 16584191
2024 Crystal structures of M68 and M87 HVRs in complex with a C4BP fragment reveal distinct C4BP-binding sequence patterns beyond the previously characterized M2 and M22 patterns; mutagenesis identified critical amino acids for C4BP binding in each pattern type. These patterns are also present in M-like Enn proteins, enabling C4BP recruitment. X-ray crystallography of HVR-C4BP fragment complexes; site-directed mutagenesis of M proteins and Enn proteins; C4BP binding assays The Journal of biological chemistry High 38879009
1996 Streptococcal surface molecules bind C4BP at a site overlapping and indistinguishable from the C4b binding site on CCP1-3 of the alpha-chain, suggesting molecular mimicry of C4b epitopes by bacterial surface proteins. Competitive inhibition assays with anti-C4BP monoclonal antibodies and C4b; binding assays with C4BP mutants; mapping to SCR 1-3 Journal of immunology Medium 8943398
2001 Binding of C4BP to the hypervariable region (HVR) of streptococcal M22 protein contributes to phagocytosis resistance; anti-HVR antibodies that block C4BP binding cause opsonization, a short HVR deletion eliminates C4BP binding and reduces phagocytosis resistance, and excess purified C4BP blocks opsonizing antibody effects. Opsonization assays; antibody inhibition of C4BP binding; HVR deletion mutagenesis; competitive addition of purified C4BP to phagocytosis system Molecular microbiology High 11703674
2019 C4BP(β-) isoform (lacking the beta-chain) exerts a novel immunomodulatory activity that 'reprograms' monocyte-derived dendritic cells from a pro-inflammatory to an anti-inflammatory/tolerogenic state; incorporation of the beta-chain into the oligomer interferes with this activity. The CCP6 domain of the C4BP alpha-chain (in PRP6-HO7 construct) is sufficient for immunomodulatory activity independent of complement regulatory function. In vivo lupus-prone mouse model; histology; anti-dsDNA antibody and complement deposition measurements; transcriptional profiling; cytokine profiling; immunohistochemistry; monocyte-derived DC reprogramming assays Kidney international / Frontiers in immunology Medium 31982108 35547734

Source papers

Stage 0 corpus · 78 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
1995 Ig-binding surface proteins of Streptococcus pyogenes also bind human C4b-binding protein (C4BP), a regulatory component of the complement system. Journal of immunology (Baltimore, Md. : 1950) 160 7995956
1988 A physical map of the human regulator of complement activation gene cluster linking the complement genes CR1, CR2, DAF, and C4BP. The Journal of experimental medicine 131 2450163
2012 Leptospiral immunoglobulin-like proteins interact with human complement regulators factor H, FHL-1, FHR-1, and C4BP. The Journal of infectious diseases 119 22291192
2003 C4b-binding protein (C4BP) activates B cells through the CD40 receptor. Immunity 106 12818164
2001 Structural requirements for the complement regulatory activities of C4BP. The Journal of biological chemistry 105 11369776
1996 A highly variable region in members of the streptococcal M protein family binds the human complement regulator C4BP. Journal of immunology (Baltimore, Md. : 1950) 97 8816411
1999 A cluster of positively charged amino acids in the C4BP alpha-chain is crucial for C4b binding and factor I cofactor function. The Journal of biological chemistry 92 10383431
2005 Binding of the complement inhibitor C4bp to serogroup B Neisseria meningitidis. Journal of immunology (Baltimore, Md. : 1950) 83 15879129
1985 Purification and functional analysis of the polymorphic variants of the C3b/C4b receptor (CR1) and comparison with H, C4b-binding protein (C4bp), and decay accelerating factor (DAF). Journal of immunology (Baltimore, Md. : 1950) 82 3161944
1997 Bordetella pertussis binds the human complement regulator C4BP: role of filamentous hemagglutinin. Infection and immunity 75 9284130
2010 Functional characterization of LcpA, a surface-exposed protein of Leptospira spp. that binds the human complement regulator C4BP. Infection and immunity 73 20404075
2008 The oligomerization domain of C4-binding protein (C4bp) acts as an adjuvant, and the fusion protein comprised of the 19-kilodalton merozoite surface protein 1 fused with the murine C4bp domain protects mice against malaria. Infection and immunity 73 18474650
2001 Binding of human C4BP to the hypervariable region of M protein: a molecular mechanism of phagocytosis resistance in Streptococcus pyogenes. Molecular microbiology 72 11703674
2006 Logarithmic phase Escherichia coli K1 efficiently avoids serum killing by promoting C4bp-mediated C3b and C4b degradation. Immunology 65 16556262
1996 Binding of human complement component C4b-binding protein (C4BP) to Streptococcus pyogenes involves the C4b-binding site. Journal of immunology (Baltimore, Md. : 1950) 61 8943398
2012 Lsa30, a novel adhesin of Leptospira interrogans binds human plasminogen and the complement regulator C4bp. Microbial pathogenesis 55 22732096
2001 Bordetella pertussis binds to human C4b-binding protein (C4BP) at a site similar to that used by the natural ligand C4b. European journal of immunology 55 11536176
1991 Natural anticoagulants in systemic lupus erythematosus. Deficiency of protein S bound to C4bp associates with recent history of venous thromboses, antiphospholipid antibodies, and the antiphospholipid syndrome. The Journal of rheumatology 51 1829765
2009 Capturing host-pathogen interactions by protein microarrays: identification of novel streptococcal proteins binding to human fibronectin, fibrinogen, and C4BP. FASEB journal : official publication of the Federation of American Societies for Experimental Biology 45 19417080
2019 Enolase From Aspergillus fumigatus Is a Moonlighting Protein That Binds the Human Plasma Complement Proteins Factor H, FHL-1, C4BP, and Plasminogen. Frontiers in immunology 40 31824478
1995 Isoforms of human C4b-binding protein. I. Molecular basis for the C4BP isoform pattern and its variations in human plasma. Journal of immunology (Baltimore, Md. : 1950) 40 7561113
1994 The gene coding for the beta-chain of C4b-binding protein (C4BPB) has become a pseudogene in the mouse. Genomics 39 7959726
2015 Leptospira interrogans Lsa23 protein recruits plasminogen, factor H and C4BP from normal human serum and mediates C3b and C4b degradation. Microbiology (Reading, England) 35 26614523
2012 Functional recruitment of the human complement inhibitor C4BP to Yersinia pseudotuberculosis outer membrane protein Ail. Journal of immunology (Baltimore, Md. : 1950) 32 22467648
1996 Binding of complement proteins C1q and C4bp to serum amyloid P component (SAP) in solid contra liquid phase. Scandinavian journal of immunology 32 8845035
2019 C4BP-IgM protein as a therapeutic approach to treat Neisseria gonorrhoeae infections. JCI insight 31 31661468
2003 Mutations in alpha-chain of C4BP that selectively affect its factor I cofactor function. The Journal of biological chemistry 31 12893820
2008 C4b-binding protein (C4BP) inhibits development of experimental arthritis in mice. Annals of the rheumatic diseases 30 18276745
2006 Streptococcal M protein: structural studies of the hypervariable region, free and bound to human C4BP. Biochemistry 30 16584191
1997 A region of vitamin K-dependent protein S that binds to C4b binding protein (C4BP) identified using bacteriophage peptide display libraries. The Journal of biological chemistry 30 9169428
1995 Isoforms of human C4b-binding protein. II. Differential modulation of the C4BPA and C4BPB genes by acute phase cytokines. Journal of immunology (Baltimore, Md. : 1950) 30 7561114
1983 Human C4b-binding protein, C4bp. Chymotryptic cleavage and location of the 48 kDa active fragment within C4bp. FEBS letters 28 6653778
2012 NlpI facilitates deposition of C4bp on Escherichia coli by blocking classical complement-mediated killing, which results in high-level bacteremia. Infection and immunity 27 22802341
2003 The binding of protein S and the protein S-C4BP complex to neutrophils is apoptosis dependent. Blood coagulation & fibrinolysis : an international journal in haemostasis and thrombosis 27 12945877
2009 Stringent regulation of complement lectin pathway C3/C5 convertase by C4b-binding protein (C4BP). Molecular immunology 26 19660812
2000 Positively charged amino acids at the interface between alpha-chain CCP1 and CCP2 of C4BP are required for regulation of the classical C3-convertase. Molecular immunology 25 11090879
1984 Evidence for linkage between the loci coding for the binding protein for the fourth component of human complement (C4BP) and for the C3b/C4b receptor. Proceedings of the National Academy of Sciences of the United States of America 24 6240062
2009 Functional consequences of cleavage, dissociation and exocytotic release of ZP3R, a C4BP-related protein, from the mouse sperm acrosomal matrix. Journal of cell science 23 19654207
1999 Interaction between protein S and complement C4b-binding protein (C4BP). Affinity studies using chimeras containing c4bp beta-chain short consensus repeats. The Journal of biological chemistry 23 10329721
1997 Absence of linkage between type III protein S deficiency and the PROS1 and C4BP genes in families carrying the protein S Heerlen allele. Blood 23 9108398
2002 Mapping of the sites responsible for factor I-cofactor activity for cleavage of C3b and C4b on human C4b-binding protein (C4bp) by deletion mutagenesis. Journal of biochemistry 19 12417021
2013 Complement regulator C4BP binds to Staphylococcus aureus surface proteins SdrE and Bbp inhibiting bacterial opsonization and killing. Results in immunology 18 24600566
2005 Single-step purification of human C4b-binding protein (C4BP) by affinity chromatography on a peptide derived from a streptococcal surface protein. Journal of immunological methods 18 15777933
1988 Assignment of complement components C4 binding protein (C4BP) and factor H (FH) to human chromosome 1q, using cDNA probes. Annals of human genetics 18 2977721
2012 Complement regulator C4BP binds to Staphylococcus aureus and decreases opsonization. Molecular immunology 17 22333221
1990 Genes for C4b-binding protein alpha- and beta-chains (C4BPA and C4BPB) are located on chromosome 1, band 1q32, in humans and on chromosome 13 in rats. Somatic cell and molecular genetics 16 2237642
1999 C4b-binding protein (C4BP) beta-chain Short Consensus Repeat-2 specifically contributes to the interaction of C4BP with protein S. Blood cells, molecules & diseases 15 10744423
1995 Comparative modeling of the three CP modules of the beta-chain of C4BP and evaluation of potential sites of interaction with protein S. Protein engineering 15 8869637
2019 Noncanonical immunomodulatory activity of complement regulator C4BP(β-) limits the development of lupus nephritis. Kidney international 14 31982108
2015 The recombinant LIC10508 is a plasma fibronectin, plasminogen, fibrinogen and C4BP-binding protein of Leptospira interrogans. Pathogens and disease 14 26657108
2001 C4d and C4bp deposition along the glomerular capillary walls in a patient with preeclampsia. American journal of kidney diseases : the official journal of the National Kidney Foundation 14 11136195
1996 Promoter region of the human gene coding for beta-chain of C4b binding protein. Hepatocyte nuclear factor-3 and nuclear factor-I/CTF transcription factors are required for efficient expression of C4BPB in HepG2 cells. Journal of immunology (Baltimore, Md. : 1950) 14 8598458
2014 Purification and functional characterization of C4b-binding protein (C4BP). Methods in molecular biology (Clifton, N.J.) 13 24218259
1987 Characterization of the interaction between human protein S and C4b-binding protein (C4bp). Journal of biochemistry 13 2962995
2022 Laminin G1 residues of protein S mediate its TFPI cofactor function and are competitively regulated by C4BP. Blood advances 12 34731882
2003 Genetic determinants of variation in the plasma levels of the C4b-binding protein (C4BP) in Spanish families. Immunogenetics 12 12671737
1998 A monomeric human C4b-binding protein (C4bp) more efficiently inactivates C3b than natural C4bp: participation of C-terminal domains in factor I-cofactor activity. Molecular immunology 12 9809581
2015 An evaluation of association between common variants in C4BPB/C4BPA genes and schizophrenia. Neuroscience letters 10 25660618
1998 Lack of sequence variations in the C4b-BP beta-chain in patients with type III protein S deficiency bearing the Ser 460 to Pro mutation: description of two new intragenic isomorphisms in the C4b-BP beta-chain gene (C4BPB). British journal of haematology 10 9576175
1987 Determination of C4b.C4-bp complex formed by the activation of classical complement pathway using an enzyme-linked immunosorbent assay. Journal of immunological methods 10 3500239
2022 The Hidden Side of Complement Regulator C4BP: Dissection and Evaluation of Its Immunomodulatory Activity. Frontiers in immunology 9 35547734
2021 Serum Complement Activation by C4BP-IgM Fusion Protein Can Restore Susceptibility to Antibiotics in Neisseria gonorrhoeae. Frontiers in immunology 9 34539665
2000 The interaction between anticoagulant protein S and complement regulatory C4b-binding protein (C4BP). Trends in cardiovascular medicine 9 11150733
1988 Derivation of the sequence of the signal peptide in human C4b-binding protein and interspecies cross-hybridisation of the C4bp cDNA sequence. FEBS letters 9 3378624
2006 The complement regulator C4b-binding protein (C4BP) interacts with both the C4c and C4dg subfragments of the parent C4b ligand: evidence for synergy in C4BP subsite binding. Biochemistry 8 16819837
2000 A cluster of positively charged amino acids in the alpha-chain of C4b-binding protein (C4BP) is pivotal for the regulation of the complement system and the interaction with bacteria. Scandinavian journal of clinical and laboratory investigation. Supplementum 8 11317941
2023 C4BP(β-)-mediated immunomodulation attenuates inflammation in DSS-induced murine colitis and in myeloid cells from IBD patients. Pharmacological research 6 37806602
2022 Interactions of Candida tropicalis pH-related antigen 1 with complement proteins C3, C3b, factor-H, C4BP and complement evasion. Immunobiology 6 36495597
2008 Regulatory mechanisms of C4b-binding protein (C4BP)alpha and beta expression in rat hepatocytes by lipopolysaccharide and interleukin-6. Journal of thrombosis and haemostasis : JTH 6 18752574
1985 Does the mouse C4-binding protein gene (C4BP) map in the H-2 region? Immunogenetics 5 3988321
1999 Consumption of C4b-binding protein (C4BP) during in vivo activation of the classical complement pathway. Clinical and experimental immunology 4 10337010
2024 Conservation of C4BP-binding sequence patterns in Streptococcus pyogenes M and Enn proteins. The Journal of biological chemistry 2 38879009
2013 Characterization of the ovine complement 4 binding protein-beta (C4BPB) chain as a serum biomarker for enhanced diagnosis of sheep scab. Molecular and cellular probes 2 23542335
1995 One-step sandwich enzyme immunoassays for human C4b-binding protein (C4BP) and protein S-C4BP complex using monoclonal antibodies. Clinica chimica acta; international journal of clinical chemistry 2 7758211
2026 C4BP occludes the non-opsonic interaction of Neisseria gonorrhoeae with human neutrophil CEACAMs. bioRxiv : the preprint server for biology 0 41648161
2025 Culture-attenuated pathogenic Leptospira lose the ability to survive complement lytic activity due to decreased C4BP uptake. Microbes and infection 0 41349955
2024 Conservation of C4BP-binding Sequence Patterns in Streptococcus pyogenes M and Enn Proteins. bioRxiv : the preprint server for biology 0 38712057
2024 Survival of Borrelia burgdorferi Strain B31 in Human Serum Is Not Dependent on C4BP Binding to the Bacterial Surface. Pathogens (Basel, Switzerland) 0 39599529