Affinage

C4BPA

C4b-binding protein alpha chain · UniProt P04003

Length
597 aa
Mass
67.0 kDa
Annotated
2026-04-28
90 papers in source corpus 25 papers cited in narrative 23 extracted findings

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

C4BPA is the principal complement-regulatory subunit of the multimeric C4b-binding protein (C4BP) complex, functioning as an obligate cofactor for serine protease factor I in the proteolytic inactivation of C4b and C3b, thereby suppressing classical, lectin, and alternative complement pathway convertases (PMID:11369776, PMID:10383431, PMID:12893820, PMID:19660812). The C4b-binding site maps to a cluster of positively charged residues (R39, R64, R66) at the CCP1–CCP2 interface, while CCP3 residues K126/K128 and F144/F149 are selectively required for cofactor catalytic function distinct from substrate binding; CCP1–3 mediate C4b regulation and CCP1–5 are needed for C3b cofactor activity (PMID:10383431, PMID:12893820, PMID:12417021). Beyond complement regulation, C4BPA binds CD40 on B cells and trophoblasts to activate NF-κB signaling, promoting B cell proliferation, IgE class switching, and pro-labor gene expression, and its CCP6 domain independently reprograms dendritic cells toward a tolerogenic phenotype (PMID:12818164, PMID:30940885, PMID:35547734). C4BPA is S-palmitoylated at its N-terminal cysteine for epididymosomal loading onto sperm to confer complement protection, and can interact intracellularly with RelA to stabilize IκBα and modulate apoptotic sensitivity (PMID:39370067, PMID:33205012).

Mechanistic history

Synthesis pass · year-by-year structured walk · 14 steps
  1. 1983 Medium

    Initial biochemistry established that the C4b-regulatory activity of C4BP resides in the N-terminal portion of each subunit chain, defining the functional architecture of the multimeric molecule.

    Evidence Chymotryptic cleavage yielding a 48 kDa N-terminal fragment with retained C4b cofactor activity

    PMID:6653778

    Open questions at the time
    • Exact domain boundaries not resolved
    • No identification of individual residues required for binding
  2. 1995 Medium

    Transcriptional regulation of C4BPA was defined: hepatic-restricted expression depends on HNF1 binding to a TATA-less promoter, and cytokines (IL-6, IFN-γ, TNF-α) differentially regulate C4BPA versus C4BPB mRNA to control circulating isoform ratios during acute-phase responses.

    Evidence Promoter deletion/EMSA in hepatocyte cell lines; cytokine dose-response Northern blots in Hep3B; COS cell co-transfection isoform reconstitution

    PMID:7561113 PMID:7561114 PMID:7772049

    Open questions at the time
    • Chromatin-level regulatory elements not mapped
    • In vivo confirmation of isoform ratio control by transcription in human acute-phase limited to correlative data
  3. 1999 High

    Site-directed mutagenesis pinpointed the C4b-binding site to positively charged residues R39, R64, and R66 at the CCP1–CCP2 interface, simultaneously identifying this region as a heparin-binding site and establishing its role in factor I cofactor function.

    Evidence R39Q, R64Q/R66Q, and triple-mutant recombinant C4BP; C4b binding and factor I cofactor assays

    PMID:10383431

    Open questions at the time
    • No structural data for the C4b–CCP1-2 interface
    • Heparin-binding significance in vivo unclear
  4. 1999 High

    The protein S–C4BP interaction was mapped to C4BPB SCR-1 (with SCR-2 augmenting affinity), establishing how C4BP sequesters the anticoagulant cofactor protein S.

    Evidence Chimeric C4BPB SCR–tPA constructs; protein S binding and APC cofactor assays

    PMID:10329721 PMID:10744423

    Open questions at the time
    • Atomic-resolution structure of the protein S–C4BPB interface not determined
    • Regulation of complex dissociation unknown
  5. 2001 High

    Systematic deletion mutagenesis resolved the domain requirements for C4b versus C3b cofactor activity: CCP1–3 are required for C4b binding while CCP1–5 are needed for C3b, and oligomeric structure enhances cell-surface C4b degradation over monomeric forms.

    Evidence 19 recombinant C4BP deletion/insertion variants; C4b and C3b binding and factor I cofactor assays

    PMID:11369776 PMID:12417021

    Open questions at the time
    • Mechanism by which multivalency enhances surface-level regulation not structurally resolved
    • Relative contributions of avidity versus conformational effects undetermined
  6. 2003 High

    CCP3 residues K126/K128 and F144/F149 were shown to be selectively essential for cofactor catalytic function without affecting C4b/C3b binding or decay acceleration, dissecting the cofactor conformational mechanism from substrate recognition.

    Evidence Site-directed mutagenesis; SPR binding plus factor I cofactor and C3-convertase decay assays

    PMID:12893820

    Open questions at the time
    • No structural basis for how these residues remodel C4b/C3b to expose factor I cleavage sites
  7. 2003 High

    C4BPA was found to bind CD40 on B cells at a site distinct from CD40L, activating NF-κB-dependent proliferation and IgE class switching — establishing a complement-independent immunomodulatory role.

    Evidence Direct binding assays; B cell activation in wild-type, CD40-deficient, and IKKγ/NEMO-deficient patient B cells; tonsil germinal center co-localization

    PMID:12818164

    Open questions at the time
    • Structural identity of the C4BPA–CD40 interface unknown
    • Physiological significance in germinal center responses not demonstrated in vivo
  8. 2006 Medium

    SPR analysis revealed that C4BPA engages C4b through adjacent but allosterically coupled subsites for C4c and C4dg fragments, explaining cooperative binding.

    Evidence SPR with purified C4c and C4dg subfragments against wild-type and mutant C4BP; ionic-strength titration

    PMID:16819837

    Open questions at the time
    • No co-crystal structure of C4BPA–C4b to validate two-subsite model
    • Only a single lab report
  9. 2019 Medium

    Fetal exosomal C4BPA was shown to activate non-canonical NF-κB (p100→p52 processing) via CD40 on placental trophoblast, linking C4BPA to pro-labor signaling.

    Evidence Cord blood exosome proteomics; structural analysis; trophoblast p100-to-p52 processing assay

    PMID:30940885

    Open questions at the time
    • In vivo necessity for labor induction not demonstrated
    • Relative contribution versus CD40L not tested
  10. 2020 Medium

    An intracellular role for C4BPA was identified: it interacts with NF-κB subunit RelA, stabilizes IκBα–RelA complexes, and sensitizes cancer cells to oxaliplatin-induced apoptosis.

    Evidence Co-immunoprecipitation of C4BPA–RelA; patient-mutation cell lines; IκBα stabilization assays; xenograft model

    PMID:33205012

    Open questions at the time
    • Mechanism of C4BPA nuclear/cytoplasmic entry uncharacterized
    • Generalizability beyond cancer cell lines uncertain
  11. 2022 Medium

    The CCP6 domain alone (in oligomeric form) was shown to reprogram monocyte-derived DCs to a tolerogenic phenotype independently of complement regulation, extending C4BPA immunomodulation beyond CD40-mediated signaling.

    Evidence Recombinant CCP6 oligomer treatment of human monocyte-derived DCs; surface marker flow cytometry; cytokine ELISA; T cell alloproliferation assays

    PMID:35547734

    Open questions at the time
    • Receptor on DCs mediating CCP6 recognition unidentified
    • In vivo tolerogenic function not demonstrated
  12. 2022 High

    C4BP beta-chain binding to protein S was shown to competitively abolish protein S cofactor enhancement of TFPIα, revealing C4BP as a regulator of the TFPI anticoagulant pathway in addition to the APC pathway.

    Evidence Glycosylation scanning and alanine scanning mutagenesis of protein S LG1 domain; FXa inhibition assays with C4BP beta-chain

    PMID:34731882

    Open questions at the time
    • In vivo impact on TFPI-dependent anticoagulation not tested in animal models
  13. 2024 Medium

    S-palmitoylation of C4BPA at N-terminal cysteines by ZDHHC8 in epididymal epithelium was identified as the mechanism for C4BPA loading onto epididymosomes and transfer to sperm, where it provides complement C4 protection and maintains motility.

    Evidence Palmitoylation site mutagenesis (C15S, C13S/C23S); epididymosome fractionation; sperm complement challenge and motility assays in mouse and pig

    PMID:39370067 PMID:41619901

    Open questions at the time
    • Male fertility consequence of C4BPA palmitoylation loss not assessed in knockout animals
    • Contribution relative to other complement regulators on sperm not quantified
  14. 2025 Medium

    In gastric cancer, C4BPA was found to promote tumor growth via JAK2/STAT3 activation and to generate C5a that polarizes macrophages to an M2-like phenotype through C5aR1/STAT3, defining a tumor-immune crosstalk axis.

    Evidence C4BPA knockdown/overexpression in GC cell lines and organoids; xenograft model; THP-1 macrophage co-culture with C5a rescue and C5aR1 inhibition

    PMID:41237697

    Open questions at the time
    • Mechanism by which C4BPA increases C5a generation not resolved
    • Single-lab finding not yet replicated

Open questions

Synthesis pass · forward-looking unresolved questions
  • No high-resolution co-crystal structure of C4BPA bound to C4b or CD40 exists; the DC receptor for CCP6-mediated tolerogenic reprogramming is unidentified; and the physiological significance of intracellular C4BPA–RelA interaction outside cancer contexts is unknown.
  • Structural basis of C4b and CD40 recognition at atomic resolution
  • Identity of DC receptor for CCP6
  • In vivo relevance of intracellular C4BPA functions

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0098772 molecular function regulator activity 7 GO:0048018 receptor ligand activity 2
Localization
GO:0005576 extracellular region 5 GO:0005829 cytosol 1 GO:0031410 cytoplasmic vesicle 1
Pathway
R-HSA-168256 Immune System 8 R-HSA-162582 Signal Transduction 4 R-HSA-109582 Hemostasis 2
Partners
C3C4BC4BPBCD40CFIPROS1RELAZDHHC8
Complex memberships
C4b-binding protein (C4BP)

Evidence

Reading pass · 23 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2001 The N-terminal CCP domains 1–3 of the C4BPA alpha-chain are required for C4b binding and complement regulatory activity; CCP2 and CCP3 are most critical, and spatial arrangement (interdomain linkers) between CCP1-4 is required for full function. Polymeric structure confers greater efficiency in degrading cell-surface C4b compared to monomeric variants. Recombinant deletion and alanine-insertion mutagenesis of 19 C4BP variants; functional assays for C4b binding and factor I cofactor activity 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 C4BPA alpha-chain constitutes the C4b-binding site; mutations at these residues reduce C4b binding affinity up to 140-fold and impair factor I cofactor activity. This site is also a specific heparin-binding site. Site-directed mutagenesis (R39Q, R64Q/R66Q, triple mutant); C4b-binding assays; factor I cofactor degradation assays; heparin binding The Journal of biological chemistry High 10383431
2003 Mutations K126Q/K128Q and F144S/F149S in CCP3 of the C4BPA alpha-chain selectively abolish factor I cofactor activity without affecting C4b/C3b binding affinity or C3-convertase decay acceleration, identifying a region specifically required for the cofactor conformational mechanism distinct from ligand binding. Site-directed mutagenesis; surface plasmon resonance binding assays; factor I cofactor degradation 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 the C4BPA alpha-chain are required for prevention of C3-convertase assembly, acceleration of its decay, and factor I cofactor activity for C4b cleavage in fluid phase. Recombinant C4BP mutants (Arg/Lys/His to Gln); C3-convertase assembly inhibition and decay acceleration assays; fluid-phase factor I cofactor assays Molecular immunology High 11090879
2002 SCR2 of the C4BPA alpha-chain is indispensable for C4b binding; SCR2 and SCR3 are required for factor I-mediated C4b cleavage; SCR1–5 participate in C3b cofactor activity with SCR2–4 being absolutely required. Different sets of CCP domains mediate C3b versus C4b cofactor activity. SCR-deletion mutants of recombinant multimeric C4BP; C3b/C4b-Sepharose binding assays; ELISA; fluid-phase cofactor assays Journal of biochemistry High 12417021
2009 C4BPA-containing C4BP regulates the lectin pathway C3/C5 convertase with ~7–13-fold greater affinity for C4b deposited via the lectin pathway than via the classical pathway; at high C4b density, all seven alpha-chains simultaneously engage C4b binding (up to ~8 C4b per C4BP heptamer). Functional complement assays on zymosan and mannan-coated erythrocytes; C4b density titration; IC50 determination for C3 and C5 convertase inhibition Molecular immunology Medium 19660812
2006 C4BPA alpha-chain interacts with both the C4c and C4dg subfragments of C4b via adjacent but distinct subsites; filling of the C4dg subsite allosterically increases C4c binding affinity 2–3-fold, revealing synergy between subsites within each CCP1-3 unit. Surface plasmon resonance binding of C4c and C4dg to wild-type and mutant C4BP; cross-competition experiments; ionic-strength titration Biochemistry Medium 16819837
2003 The C4BPA alpha-chain binds directly to CD40 on human B cells at a site distinct from the CD40L binding site, inducing B cell proliferation, upregulation of CD54 and CD86, and IL-4-dependent IgE isotype switching; this activity is absent in B cells from CD40- or IKKγ/NEMO-deficient patients. C4BP co-localizes with B cells in germinal centers of human tonsils. Direct binding assays; B cell activation and isotype switching assays; patient-derived B cells (CD40-deficient, IKKγ/NEMO-deficient); immunofluorescence co-localization in tonsil tissue Immunity High 12818164
1999 Protein S binds to the C4BP beta-chain (C4BPB) primarily through SCR-1, with SCR-2 contributing to enhance affinity up to 5-fold; C4BPB SCR-2 specifically augments SCR-1 binding to protein S, and binding to SCR-1-containing constructs reduces protein S cofactor activity for activated protein C. Chimeric constructs of C4BPB SCRs fused to tPA; protein S binding assays; activated protein C cofactor activity assays The Journal of biological chemistry High 10329721 10744423
1997 Residues 447–460 of protein S (within the laminin G1 domain region, around position 450) constitute a binding site for the C4BP beta-chain, as identified by phage-display peptide library selection and confirmed by synthetic peptide inhibition and direct biophysical binding measurements. Bacteriophage peptide display library selection; synthetic peptide inhibition assays; near-UV circular dichroism and tryptophan fluorescence polarization titrations The Journal of biological chemistry Medium 9169428
2022 Protein S residues Lys255, Glu257, Asp287, Arg410, Lys423, and Glu424 within the LG1 domain are critical for TFPI cofactor function; C4BP beta-chain binding to protein S at this same region almost completely abolishes protein S-mediated enhancement of TFPIα, establishing competitive regulation of the TFPI anticoagulant pathway by C4BP. N-linked glycosylation scanning mutagenesis; alanine scanning; FXa inhibition assays; C4BP beta-chain expression and binding; plasma TFPI cofactor assays Blood advances High 34731882
1995 C4BPA gene expression is controlled by a hepatic-specific promoter within 369 bp upstream of the transcription start site; the hepatic transcription factor HNF1 binds at −38 bp and is absolutely required for promoter activity, explaining liver-restricted C4BPA expression. The promoter lacks a TATA box. Promoter deletion analysis by transfection; HNF1 binding by footprinting/EMSA; hepatocyte vs. non-hepatocyte cell line transfection comparison The Biochemical journal Medium 7772049
1995 C4BP plasma isoform pattern (α7β1, α7β0, α6β1) is determined by the relative expression levels of the C4BPA and C4BPB genes; genetic factors segregating with the RCA gene cluster control isoform proportions, as demonstrated by HepG2/Hep3B secretion studies and COS cell transfections with different alpha/beta chain ratios. Hepatocyte cell line (HepG2, Hep3B) secretion analysis; COS cell co-transfection with varying C4BPA/C4BPB ratios; Western blot isoform characterization Journal of immunology Medium 7561113
1995 IL-6, IL-1β, and IFN-γ upregulate both C4BPA and C4BPB mRNA in Hep3B cells; TNF-α downregulates both; IFN-γ combined with TNF-α synergistically induces C4BPA mRNA ~10-fold while only marginally increasing C4BPB mRNA, providing a mechanism to maintain C4BPB steady-state levels during acute phase induction. Cytokine treatment of Hep3B cells; Northern blot analysis of C4BPA and C4BPB mRNA; serial plasma isoform analysis in acute phase patients Journal of immunology Medium 7561114
2008 LPS decreases C4BPα and C4BPβ expression in rat hepatocytes via the NF-κB and MEK/ERK pathways; IL-6 specifically increases C4BPβ expression via the STAT-3 pathway, leading to increased plasma PS–C4BP complex and decreased anticoagulant protein S activity. LPS and IL-6 treatment of isolated rat hepatocytes in vitro and in vivo; NF-κB, MEK/ERK, and STAT-3 pathway inhibitors; Western blot and RT-PCR; plasma PS activity and PS-C4BP complex measurement Journal of thrombosis and haemostasis Medium 18752574
2020 C4BPA is expressed intracellularly in cancer cells where it interacts with the NF-κB family member RelA; elevated intracellular C4BPA increases IκBα expression and stabilizes inhibitory IκBα–RelA complexes, sensitizing cells to oxaliplatin-induced apoptosis in vitro and in vivo. Co-immunoprecipitation of C4BPA with RelA; cancer cell lines with patient-specific C4BPA mutations; IκBα expression and complex stability assays; oxaliplatin apoptosis assays in vitro and xenograft model iScience Medium 33205012
2019 Fetal C4BPA (from fetal cord blood exosomes) binds CD40 on placental villous trophoblast to activate non-canonical NF-κB processing of p100 to p52, inducing pro-labor gene expression; this was supported by computational, crystal structural, and gene functional analyses. Proteomics of fetal cord blood exosomes; crystal structural analysis; gene functional assays in placental trophoblast cells; p100-to-p52 processing assay Scientific reports Medium 30940885
1983 Chymotryptic cleavage of C4BP yields a 48 kDa N-terminal fragment (from each subunit chain) that retains C4b-regulatory activity; the C4b-binding/active site is located in the N-terminal portion of the subunit chain, and C4BP is composed of 6–8 disulfide-linked 75 kDa subunit chains. Chymotrypsin cleavage; fragment purification; N-terminal amino acid sequencing; functional activity assay of isolated fragment FEBS letters Medium 6653778
1998 A monomeric membrane-anchored form of C4BPA (all 8 SCRs, GPI-anchored) acts as a more efficient factor I cofactor for C3b inactivation than natural multimeric C4BP; blocking studies showed that both the 48 kDa N-terminal fragment and C-terminal domains near the oligomerization region contribute to high C3b-inactivating cofactor activity. Expression of monomeric GPI-anchored C4BP on swine endothelial cells; fluid-phase factor I cofactor assays with methylamine-treated C3 and C4; monoclonal antibody blocking studies Molecular immunology Medium 9809581
2003 Protein S and the C4BP–protein S complex bind to apoptotic (but not healthy) neutrophils; binding is mediated through the Gla domain of protein S, which recognizes negatively charged phospholipids exposed on apoptotic cells, demonstrating that C4BP is recruited to apoptotic surfaces via its protein S partner. Binding assays with apoptotic vs. non-apoptotic neutrophil populations; anti-Gla domain monoclonal antibody blocking; flow cytometry Blood coagulation & fibrinolysis Medium 12945877
2024 S-palmitoylation of C4BPA at Cys15 (mouse) / Cys13 and Cys23 (pig, by ZDHHC8) in epididymal epithelial cells is required for C4BPA enrichment into epididymosomes and transfer to sperm surface; palmitoylated C4BPA on sperm protects against complement C4-mediated damage and maintains sperm motility, while the C15S (or C13S/C23S) mutant loses this protective function. Palmitoylation inhibition studies; C15S and C23S mutagenesis; immunofluorescence localization; sperm motility assays; complement C4 challenge assays; epididymosome fractionation International journal of biological macromolecules / Biochimica et biophysica acta Medium 39370067 41619901
2025 C4BPA promotes gastric cancer cell proliferation and motility via activation of JAK2/STAT3 phosphorylation in tumor cells and increases C3a and C5a production; C4BPA-derived C5a signals through C5aR1 on macrophages to activate STAT3 and drive M2-like polarization, establishing a C4BPA→C5a→C5aR1→STAT3 axis in tumor-immune crosstalk. C4BPA knockdown and overexpression in GC cell lines; patient-derived GC organoids; subcutaneous xenograft mouse model; JAK2/STAT3 phosphorylation assays; C3a/C5a measurement; THP-1 macrophage co-culture; recombinant C5a rescue; C5aR1 inhibition International immunopharmacology Medium 41237697
2022 The CCP6 domain of the C4BPA alpha-chain (in oligomeric form, PRP6-HO7) is sufficient to reprogram pro-inflammatory monocyte-derived dendritic cells to an anti-inflammatory tolerogenic state, downregulating CD83, HLA-DR, CD86, CD80, CD40, IL-12, and TNF-α, and inhibiting T cell alloproliferation; this immunomodulatory activity is independent of complement regulatory activity. Recombinant CCP6-oligomer (PRP6-HO7) treatment of monocyte-derived DCs; flow cytometry for surface markers; cytokine ELISA; T cell alloproliferation assays; endocytosis and chemotaxis assays; comparison with full-length C4BP isoforms Frontiers in immunology Medium 35547734

Source papers

Stage 0 corpus · 90 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
2016 Identification of a novel serum biomarker for pancreatic cancer, C4b-binding protein α-chain (C4BPA) by quantitative proteomic analysis using tandem mass tags. British journal of cancer 78 27657339
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
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
2020 Intracellular C4BPA Levels Regulate NF-κB-Dependent Apoptosis. iScience 21 33205012
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
2022 C4BPA: A Novel Co-Regulator of Immunity and Fat Metabolism in the Bovine Mammary Epithelial Cells. Frontiers in genetics 16 35173767
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
2019 Fetal lung C4BPA induces p100 processing in human placenta. Scientific reports 15 30940885
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
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
2022 Association Between Plasma Exosomes S100A9/C4BPA and Latent Tuberculosis Infection Treatment: Proteomic Analysis Based on a Randomized Controlled Study. Frontiers in microbiology 12 35935235
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
2017 Association of single nucleotide polymorphisms in the 5' upstream region of the C4BPA gene with essential hypertension in a northeastern Han Chinese population. Molecular medicine reports 11 28627632
2022 Potential biomarkers of spinal dural arteriovenous fistula: C4BPA and C1QA. Journal of neuroinflammation 10 35733178
2015 An evaluation of association between common variants in C4BPB/C4BPA genes and schizophrenia. Neuroscience letters 10 25660618
1995 Expression of the human gene coding for the alpha-chain of C4b-binding protein, C4BPA, is controlled by an HNF1-dependent hepatic-specific promoter. The Biochemical journal 10 7772049
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 The role of S-palmitoylation of C4BPA in regulating murine sperm motility and complement resistance. International journal of biological macromolecules 3 39370067
2024 Conservation of C4BP-binding sequence patterns in Streptococcus pyogenes M and Enn proteins. The Journal of biological chemistry 2 38879009
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
2025 Identification of serum C4BPA as a potential diagnostic marker of right ventricular remodelling via proteomic analysis. ESC heart failure 1 40237358
2024 Altered Expression of C4BPA and CXCL1 Genes in the Endometrium of Patients with Recurrent Implantation Failure after In Vitro Fertilization and Thin Endometrium. Diagnostics (Basel, Switzerland) 1 39272751
2026 Palmitoylation of C4BPA in porcine epididymosomes mitigates complement C4-mediated damage to sperm. Biochimica et biophysica acta. Molecular and cell biology of lipids 0 41619901
2026 C4BP occludes the non-opsonic interaction of Neisseria gonorrhoeae with human neutrophil CEACAMs. bioRxiv : the preprint server for biology 0 41648161
2026 Knockout of the C4BPA Gene Promotes Mitophagy via Activation of the Pink1/Parkin Pathway and Alleviates the Inflammatory Response by Inhibiting the NF-κB Signalling Pathway in Bovine Mammary Epithelial Cells. Veterinary sciences 0 41745945
2026 Impact of C4BPA on Muscle progenitor cell differentiation: insights for Duchenne muscular dystrophy treatment. Cell death & disease 0 41851078
2025 Identification of C4BPA as a genetically informed drug target in NSCLC: an integrative single-cell and multi-omics study based on the druggable genes. Human genomics 0 41053817
2025 Tumor-derived C4BPA promotes macrophage M2-like polarization through C5a -C5aR1-STAT3 axis and drives gastric cancer progression. International immunopharmacology 0 41237697
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