Gene Symbol: C4B
Description: complement C4B (Chido blood group)
Alias: C4B1, C4B12, C4B2, C4B3, C4B5, C4BD, C4B_2, C4F, CO4, CPAMD3, complement C4-B, C3 and PZP-like alpha-2-macroglobulin domain-containing protein 3, Chido form of C4, basic complement C4, complement C4B1a, complement component 4B (Chido blood group)
Species: human
Products:     C4B

Top Publications

  1. Yu C, Belt K, Giles C, Campbell R, Porter R. Structural basis of the polymorphism of human complement components C4A and C4B: gene size, reactivity and antigenicity. EMBO J. 1986;5:2873-81 pubmed
    The human complement components C4A and C4B are highly homologous proteins, but they show markedly different, class-specific, chemical reactivities...
  2. Puah S, Lian L, Chew C, Chua K, Tan S. A study of association of the complement C4 mutations with systemic lupus erythematosus in the Malaysian population. Lupus. 2007;16:750-4 pubmed
    ..C4A*Q0 was found in two out of the 130 control samples, while C4B*Q0 was present in two out of the 130 SLE patients...
  3. Fernando M, Boteva L, Morris D, Zhou B, Wu Y, Lokki M, et al. Assessment of complement C4 gene copy number using the paralog ratio test. Hum Mutat. 2010;31:866-74 pubmed publisher
    ..association with two restriction enzyme digest variant ratio tests (REDVRs) to determine total C4 GCN, C4A GCN, and C4B GCN...
  4. Mougey R. A review of the Chido/Rodgers blood group. Immunohematology. 2010;26:30-8 pubmed
    ..The recognition of the extreme polymorphism of the C4 gene and the gene complex RCCX should lead to more insights in the understanding of disease risk and potential treatment. ..
  5. Man X, Luo H, Li X, Yao Y, Mao C, Zhang Y. Polymerase chain reaction based C4AQ0 and C4BQ0 genotyping: association with systemic lupus erythematosus in southwest Han Chinese. Ann Rheum Dis. 2003;62:71-3 pubmed
    ..It is suggested that deficiency of C4A (not due to a 2 bp insertion in exon 29), but not C4B or C2, may be a risk factor for acquiring SLE in south west Han Chinese; this results in increased risk of renal ..
  6. Ittiprasert W, Kantachuvesiri S, Pavasuthipaisit K, Verasertniyom O, Chaomthum L, Totemchokchyakarn K, et al. Complete deficiencies of complement C4A and C4B including 2-bp insertion in codon 1213 are genetic risk factors of systemic lupus erythematosus in Thai populations. J Autoimmun. 2005;25:77-84 pubmed
    The complement component C4 is encoded by two genes: C4A and C4B on human chromosome 6p in the major histocompatibility complex (MHC)...
  7. Seppanen M, Lokki M, Notkola I, Mattila K, Valtonen V, Nieminen A, et al. Complement and c4 null alleles in severe chronic adult periodontitis. Scand J Immunol. 2007;65:176-81 pubmed
    ..4, 95% confidence interval 1.1-5.5, P = 0.032). Changes in complement levels may reflect chronic, recurring inflammation. C4 gene deficiencies are associated with predisposition to chronic periodontitis. ..
  8. Paakkanen R, Vauhkonen H, Eronen K, Järvinen A, Seppanen M, Lokki M. Copy number analysis of complement C4A, C4B and C4A silencing mutation by real-time quantitative polymerase chain reaction. PLoS ONE. 2012;7:e38813 pubmed publisher
    Low protein levels and copy number variation (CNV) of the fourth component of human complement (C4A and C4B) have been associated with various diseases...
  9. Yu C. The complete exon-intron structure of a human complement component C4A gene. DNA sequences, polymorphism, and linkage to the 21-hydroxylase gene. J Immunol. 1991;146:1057-66 pubmed
    The human complement component C4A and C4B genes are located within the class III region of the MHC. The polymorphic C4 genes are highly complex including variations in class (isotype), size, and number of genes...

More Information

Publications118 found, 100 shown here

  1. Yang Z, Mendoza A, Welch T, Zipf W, Yu C. Modular variations of the human major histocompatibility complex class III genes for serine/threonine kinase RP, complement component C4, steroid 21-hydroxylase CYP21, and tenascin TNX (the RCCX module). A mechanism for gene deletions and disease ass. J Biol Chem. 1999;274:12147-56 pubmed
    ..In a patient with congenital adrenal hyperplasia, we discovered a TNXB-TNXA recombinant with the deletion of RP2-C4B-CYP21B...
  2. Blanchong C, Chung E, Rupert K, Yang Y, Yang Z, Zhou B, et al. Genetic, structural and functional diversities of human complement components C4A and C4B and their mouse homologues, Slp and C4. Int Immunopharmacol. 2001;1:365-92 pubmed
    ..In this review, we summarize the current concepts on the 1-2-3 loci model of C4A and C4B genes in the population, factors affecting the expression levels of C4 transcripts and proteins, and the structural,..
  3. Chung E, Yang Y, Rupert K, Jones K, Rennebohm R, Blanchong C, et al. Determining the one, two, three, or four long and short loci of human complement C4 in a major histocompatibility complex haplotype encoding C4A or C4B proteins. Am J Hum Genet. 2002;71:810-22 pubmed
    The complex genetics of human complement C4 with unusually frequent variations in the size and number of C4A and C4B, as well as their neighboring genes, in the major histocompatibility complex has been a hurdle for accurate ..
  4. Wouters D, van Schouwenburg P, van der Horst A, de Boer M, Schooneman D, Kuijpers T, et al. High-throughput analysis of the C4 polymorphism by a combination of MLPA and isotype-specific ELISA's. Mol Immunol. 2009;46:592-600 pubmed publisher
    Complement factor C4 exists as two main isotypes, C4A and C4B, with different functional properties and encoded by two separate genes...
  5. Kingery S, Wu Y, Zhou B, Hoffman R, Yu C. Gene CNVs and protein levels of complement C4A and C4B as novel biomarkers for partial disease remissions in new-onset type 1 diabetes patients. Pediatr Diabetes. 2012;13:408-18 pubmed publisher
    To determine the roles of complement C4A and C4B gene copy-number variations and their plasma protein concentrations in residual insulin secretion and loss of pancreatic ?-cell function in new-onset type 1 diabetes (T1D) patients...
  6. Yang Y, Chung E, Wu Y, Savelli S, Nagaraja H, Zhou B, et al. Gene copy-number variation and associated polymorphisms of complement component C4 in human systemic lupus erythematosus (SLE): low copy number is a risk factor for and high copy number is a protective factor against SLE susceptibility in European Am. Am J Hum Genet. 2007;80:1037-54 pubmed
    ..component C4 and its associated polymorphisms in gene size (long and short) and protein isotypes (C4A and C4B) probably lead to different susceptibilities to autoimmune disease...
  7. Boteva L, Wu Y, Cortes Hernández J, Martin J, Vyse T, Fernando M. Determination of the loss of function complement C4 exon 29 CT insertion using a novel paralog-specific assay in healthy UK and Spanish populations. PLoS ONE. 2011;6:e22128 pubmed publisher
    Genetic variants resulting in non-expression of complement C4A and C4B genes are common in healthy European populations and have shown association with a number of diseases, most notably the autoimmune disease, systemic lupus ..
  8. Dragon Durey M, Rougier N, Clauvel J, Caillat Zucman S, Remy P, Guillevin L, et al. Lack of evidence of a specific role for C4A gene deficiency in determining disease susceptibility among C4-deficient patients with systemic lupus erythematosus (SLE). Clin Exp Immunol. 2001;123:133-9 pubmed
    ..8% prevalence), 41.0% of the patients exhibited a C4A deficiency and 59.0% a C4B deficiency. Half of the C4 deficiencies were due to a gene deletion...
  9. Chang C, Tung Y, Lin Y, Liao C, Chiu C, Tung T, et al. Effects of Caloric Restriction with Protein Supplementation on Plasma Protein Profiles in Middle-Aged Women with Metabolic Syndrome-A Preliminary Open Study. J Clin Med. 2019;8: pubmed publisher
    ..chromatography⁻tandem mass spectrometry analysis, the relative plasma levels of alpha-2-macroglobulin (A2M), C4b-binding protein alpha chain (C4BPA), complement C1r subcomponent-like protein (C1RL), complement component C6 (C6), ..
  10. Plubell D, Wilmarth P, Zhao Y, Fenton A, Minnier J, Reddy A, et al. Extended Multiplexing of Tandem Mass Tags (TMT) Labeling Reveals Age and High Fat Diet Specific Proteome Changes in Mouse Epididymal Adipose Tissue. Mol Cell Proteomics. 2017;16:873-890 pubmed publisher
    ..g. ARG1, CPS1), immune response/complement activation (e.g. C3, C4b, C8, C9, CFB, CFH, FGA), extracellular remodeling (e.g...
  11. Murray G. The molecular basis of leptospiral pathogenesis. Curr Top Microbiol Immunol. 2015;387:139-85 pubmed publisher
    ..proteins related to hemostasis (fibrinogen, plasmin), and soluble mediators of complement resistance (factor H, C4b-binding protein), although none of these in vitro findings has been translated to the host animal...
  12. Lopez Gonzalez I, Viana R, Sanz P, Ferrer I. Inflammation in Lafora Disease: Evolution with Disease Progression in Laforin and Malin Knock-out Mouse Models. Mol Neurobiol. 2017;54:3119-3130 pubmed publisher
    ..increased in Epm2a -/- mice aged 12 months when compared with age-matched controls, whereas C3ar1, C4b, Ccl4, CxCl10, Il1b, Il6, Tnf?, and Il10ra mRNAs are significantly upregulated in Epm2b -/- at the same ..
  13. Fokou M, Moifo B, Fongang E, Teyang A, Muna W. Characteristics of patients and patterns of chronic venous disease of the lower limbs in a referral hospital in Cameroon. J Vasc Surg Venous Lymphat Disord. 2018;6:90-95 pubmed publisher
    ..The C class included C0, 6.1%; C1, 35.4%; C2, 39.6%; C3, 42.7%; C4a, 11.9%; C4b, 4.9%; C5, 1.5%; and C6, 10.13%. The E class designated etiology as primary in 446 (88.66%), secondary in 49 (9...
  14. Blom A, Corvillo F, Magda M, Stasiłojć G, Nozal P, Pérez Valdivia M, et al. Testing the Activity of Complement Convertases in Serum/Plasma for Diagnosis of C4NeF-Mediated C3 Glomerulonephritis. J Clin Immunol. 2016;36:517-27 pubmed publisher
    ..immunoglobulins protected classical convertases from both spontaneous and inhibitor-driven decay but not from C4b proteolysis...
  15. Martin M, Blom A. Complement in removal of the dead - balancing inflammation. Immunol Rev. 2016;274:218-232 pubmed publisher
    ..Importantly, the process is tightly controlled by the binding of complement inhibitors C4b-binding protein and factor H, which attenuates late steps of complement activation and inflammation...
  16. Arumugam T, Woodruff T, Lathia J, Selvaraj P, Mattson M, Taylor S. Neuroprotection in stroke by complement inhibition and immunoglobulin therapy. Neuroscience. 2009;158:1074-89 pubmed publisher
    ..involving complement activation and generation of active fragments, such as C3a and C5a anaphylatoxins, C3b, C4b, and iC3b...
  17. Franco A, Kothary M, Gopinath G, Jarvis K, Grim C, Hu L, et al. Cpa, the outer membrane protease of Cronobacter sakazakii, activates plasminogen and mediates resistance to serum bactericidal activity. Infect Immun. 2011;79:1578-87 pubmed publisher
    ..sakazakii or Escherichia coli DH5α showed that Cpa proteolytically cleaved complement components C3, C3a, and C4b. Furthermore, a strain of C...
  18. Bartra S, Ding Y, Fujimoto L, Ring J, Jain V, Ram S, et al. Yersinia pestis uses the Ail outer membrane protein to recruit vitronectin. Microbiology. 2015;161:2174-83 pubmed publisher
    ..matrix, including fibronectin, laminin and heparan sulfate proteoglycans, and with the complement inhibitor C4b-binding protein. Here, we demonstrate that Ail-expressing Y...
  19. Silva N, Vale V, Franco P, Gontijo N, Valenzuela J, Pereira M, et al. Saliva of Rhipicephalus (Boophilus) microplus (Acari: Ixodidae) inhibits classical and alternative complement pathways. Parasit Vectors. 2016;9:445 pubmed publisher
    ..In the classical pathway, the saliva blocked C4 cleavage, and hence, deposition of C4b on the activation surface, suggesting that the inhibition occurs at some point between C1q and C4...
  20. Burillo E, Jorge I, Martinez Lopez D, Camafeita E, Blanco Colio L, Trevisan Herraz M, et al. Quantitative HDL Proteomics Identifies Peroxiredoxin-6 as a Biomarker of Human Abdominal Aortic Aneurysm. Sci Rep. 2016;6:38477 pubmed publisher
    ..antigen (HLA-I), retinol-binding protein 4, and paraoxonase/arylesterase 1 (PON1), whereas ?-2 macroglobulin and C4b-binding protein were decreased...
  21. Wu C, Xu G, Tsai S, Freed W, Lee C. Transcriptional profiles of type 2 diabetes in human skeletal muscle reveal insulin resistance, metabolic defects, apoptosis, and molecular signatures of immune activation in response to infections. Biochem Biophys Res Commun. 2017;482:282-288 pubmed publisher
    ..and notably include immune-related pathways suggestive of a response to various infectious diseases (C2, CFB, C4A, C4B, C1S, C1R, C3, HLA-DRA, HLA-DMA, HLA-DOA, and HLA-DPB1)...
  22. Lepczynski A, Herosimczyk A, Ozgo M, Skomial J, Taciak M, Barszcz M, et al. Dietary supplementation with dried chicory root triggers changes in the blood serum proteins engaged in the clotting process and the innate immune response in growing pigs. J Physiol Pharmacol. 2015;66:47-55 pubmed
    ..a significant down-regulation of apolipoprotein C-II complement component C6, C-reactive protein, CD14 antigen, C4b binding protein α and β chains, and fibrinogen...
  23. Castillo E, Leon J, Mazzei G, Abolhassani N, Haruyama N, Saito T, et al. Comparative profiling of cortical gene expression in Alzheimer's disease patients and mouse models demonstrates a link between amyloidosis and neuroinflammation. Sci Rep. 2017;7:17762 pubmed publisher
    ..Among them, expression of AD-related genes (C4a/C4b, Cd74, Ctss, Gfap, Nfe2l2, Phyhd1, S100b, Tf, Tgfbr2, and Vim) was increased in the App NL-G-F/NL-G-F ..
  24. Bartling B, Niemann K, Pliquett R, Treede H, Simm A. Altered gene expression pattern indicates the differential regulation of the immune response system as an important factor in cardiac aging. Exp Gerontol. 2019;117:13-20 pubmed publisher
    ..CCLs 6, 8, 9), proteins of the S100 family (S100s 4, 8, 9, 10, 11), complement components (C1qa, C1qb, C1qc, C3, C4b), bacteria/virus-induced genes (lysozyme 1/2, interferon-activated genes), and pro-inflammatory caspases (Casp1, ..
  25. Sharma S, Kumar G, Vashishta M, Pandey R, Rathore S, Chourasia B, et al. Biochemical characterization of Plasmodium complement factors binding protein for its role in immune modulation. Biochem J. 2018;475:2877-2891 pubmed publisher
    ..Complement Control Protein 1, PfCCp1 at asexual blood stages and its binding affinity with C3b as well as C4b proteins of human complement cascade...
  26. Dufresne J, Florentinus Mefailoski A, Ajambo J, Ferwa A, Bowden P, Marshall J. The proteins cleaved by endogenous tryptic proteases in normal EDTA plasma by C18 collection of peptides for liquid chromatography micro electrospray ionization and tandem mass spectrometry. Clin Proteomics. 2017;14:39 pubmed publisher
    ..e. FDR = 0.000000001) to E-227. A set of 528 gene symbols identified by X!TANDEM and SEQUEST including C4B showed ? fivefold variation between ice cold versus room temperature incubation...
  27. Thanei S, Trendelenburg M. Anti-C1q autoantibodies from patients with systemic lupus erythematosus induce C1q production by macrophages. J Leukoc Biol. 2017;101:481-491 pubmed publisher
    ..Finally, secreted C1q was able to activate the CP, as reflected by C4b deposition. Interestingly, anti-C1q-dependent C1q secretion could also be observed in SLE patient-derived cells...
  28. Schwahn Schreiber C, Breu F, Rabe E, Buschmann I, Döller W, Lulay G, et al. [S1 guideline on intermittent pneumatic compression (IPC)]. Hautarzt. 2018;69:662-673 pubmed publisher
    ..A target indication is thrombosis prophylaxis. IPC should be used in severe chronic venous insufficiency (stages C4b to C6), in extremity lymphedema as an add-on therapy and in peripheral arterial occlusive disease (PAOD) with ..
  29. Hasan M, Seo J, Rahaman K, Min H, Kim K, Park J, et al. Novel genes in brain tissues of EAE-induced normal and obese mice: Upregulation of metal ion-binding protein genes in obese-EAE mice. Neuroscience. 2017;343:322-336 pubmed publisher
    ..Upregulation of Cul9, Mast2, and C4b expression is significantly higher in HFD-EAE mice than ND-EAE mice...
  30. Watanabe A, Satoh K, Maniwa T, Matsumoto K. Proteomic analysis for the identification of serum diagnostic markers for joint hypermobility syndrome. Int J Mol Med. 2016;37:461-7 pubmed publisher
    ..complement system including complement C1r subcomponent (C1R), vitronectin (VTN), complement component C9 (C9), and C4b-binding protein alpha chain (C4BPA) were identified as increased proteins in sera from patients with JHS compared ..
  31. Breda L, Vasconcellos S, De Moraes Vasconcelos D, Isaac L. Binding of human complement C1 sterase inhibitor to Leptospira spp. Immunobiology. 2018;223:183-190 pubmed publisher
    ..Pathogenic Leptospira interact with Complement Regulators such as Factor H, C4b binding protein and Vitronectin avoiding Complement activation and killing by Alternative and Classical Pathways...
  32. Reilly B. Structural comparison of human C4A3 and C4B1 after proteolytic activation by C1s. Mol Immunol. 2006;43:800-11 pubmed
    ..Of the two C4 genes C4A, but not C4B, null alleles have been implicated as important independent disease susceptibility genes occurring in more than ..
  33. Nakao M, Kajiya T, Sato Y, Somamoto T, Kato Unoki Y, Matsushita M, et al. Lectin pathway of bony fish complement: identification of two homologs of the mannose-binding lectin associated with MASP2 in the common carp (Cyprinus carpio). J Immunol. 2006;177:5471-9 pubmed
    ..Both were found to associate with a serine protease that cleaves native human C4 into C4b but not C4i with a hydrolyzed thioester...
  34. Sánchez Gallego J, Groeneveld T, Krentz S, Nilsson S, Villoutreix B, Blom A. Analysis of binding sites on complement factor I using artificial N-linked glycosylation. J Biol Chem. 2012;287:13572-83 pubmed publisher
    ..is a serine protease that inhibits all complement pathways by degrading activated complement components C3b and C4b. FI functions only in the presence of several cofactors, such as factor H, C4b-binding protein, complement receptor ..
  35. Iacob S, Cicinnati V, Lindemann M, Heinemann F, Radtke A, Kaiser G, et al. Donor-Specific Anti-HLA Antibodies and Endothelial C4d Deposition-Association With Chronic Liver Allograft Failure. Transplantation. 2015;99:1869-75 pubmed publisher
    ..4-217.8 months], P < 0.0001). Screening for HLA DSA might be useful for early identification of LT recipients at increased risk of graft failure who could benefit from closer surveillance and tailored immunosuppressive regimens. ..
  36. Kolte A, Nielsen H, Steffensen R, Crespi B, Christiansen O. Inheritance of the 8.1 ancestral haplotype in recurrent pregnancy loss. Evol Med Public Health. 2015;2015:325-31 pubmed publisher
    The 8.1 ancestral haplotype (AH) (HLA-A1, C7, B8, C4AQ0, C4B1, DR3, DQ2) is a remarkably long and conserved haplotype in the human major histocompatibility complex...
  37. Grassmann F, Cantsilieris S, Schulz Kuhnt A, White S, Richardson A, Hewitt A, et al. Multiallelic copy number variation in the complement component 4A (C4A) gene is associated with late-stage age-related macular degeneration (AMD). J Neuroinflammation. 2016;13:81 pubmed publisher
    ..amplification (MLPA) to determine the copy number of the C4 gene as well as of both relevant isoforms, C4A and C4B, and assessed their association with AMD using logistic regression models...
  38. Wu B, Ouyang Z, Lyon C, Zhang W, Clift T, Bone C, et al. Plasma Levels of Complement Factor I and C4b Peptides Are Associated with HIV Suppression. ACS Infect Dis. 2017;3:880-885 pubmed publisher
    ..Complement C3b and C4b can influence HIV infection and replication, but studies have not examined their possible link to HIV controller ..
  39. Chen G, Li T, Zheng Q, Hou J, Tang S, Li W. [Differential expression and significance of complement C4b and transthyretin in proliferative vitreoretinopathy]. Zhonghua Yan Ke Za Zhi. 2011;47:726-31 pubmed
    To investigate the differential expression of complement C4b and transthyretin in proliferative vitreoretinopathy (PVR). It was a controlled experimental study...
  40. Luk A, Alba A, Butany J, Tinckam K, Delgado D, Ross H. C4d immunostaining is an independent predictor of cardiac allograft vasculopathy and death in heart transplant recipients. Transpl Int. 2015;28:857-63 pubmed publisher
    ..42; 95% CI 1.0-2.09). C4d was not associated with CMR. C4d immunostaining was a significant predictor of CAV and death but not subsequent episodes of CMR. There was also a trend toward increased graft failure. ..
  41. Qin G, Wu M, Sang N. Sulfur dioxide and benzo(a)pyrene trigger apoptotic and anti-apoptotic signals at different post-exposure times in mouse liver. Chemosphere. 2015;139:318-25 pubmed publisher
    ..e. 1d), with the suppression of the mRNA expression of complexes IV and V subunits, CO1, CO4, and ATP6...
  42. Woehl J, Takahashi D, Herrera A, Geisbrecht B, Prakash O. (1)H, (15)N, and (13)C resonance assignments of Staphylococcus aureus extracellular adherence protein domain 4. Biomol NMR Assign. 2016;10:301-5 pubmed publisher
    ..By binding to complement component C4b, Eap is able to inhibit formation of the CP/LP C3 pro-convertase...
  43. Li K, Lv X, Shi L, Liu L, Li B, Wu B. A new strategy to obtain tetranuclear cobalt(ii) metal-organic frameworks based on the [Co4(?3-OH)2] cluster: synthesis, structures and properties. Dalton Trans. 2016;45:15078-15088 pubmed
    ..This work presents a novel but effective method to design and regulate the connection number (4, 6 and 8 connected in this work) of MOFs with 4-substituted 1,2,4-triazole and rigid multicarboxylate ligands. ..
  44. Susal C, Kirschfink M, Kröpelin M, Daniel V, Opelz G. Complement activation by recombinant HIV-1 glycoprotein gp120. J Immunol. 1994;152:6028-34 pubmed
    ..Complement activation by cell-bound HIV-1 envelope glycoprotein gp120 with subsequent opsonization may be relevant for the elimination of noninfected CD4+ T cells in HIV-infected patients. ..
  45. Yuen S, Mak Y, Tang H, Yong S, Chow K, Chu K, et al. Renal allograft C4d deposition in Chinese: Hong Kong perspective. Nephrology (Carlton). 2008;13:256-63 pubmed publisher
    ..Our findings confirmed the independent prognostic value of peritubular capillary C4d staining on renal allograft survival in Chinese. ..
  46. Wu J, Guo Z, Gao Y. Dynamic changes of urine proteome in a Walker 256 tumor-bearing rat model. Cancer Med. 2017;6:2713-2722 pubmed publisher
    ..A total of 10 urinary proteins (HPT, APOA4, CO4, B2MG, A1AG, CATC, VCAM1, CALB1, CSPG4, and VTDB) changed significantly even before a tumor mass was palpable, and ..
  47. Almitairi J, Venkatraman Girija U, Furze C, Simpson Gray X, Badakshi F, Marshall J, et al. Structure of the C1r-C1s interaction of the C1 complex of complement activation. Proc Natl Acad Sci U S A. 2018;115:768-773 pubmed publisher
    ..Considerable flexibility in C1s likely facilitates C1 complex formation, activation of C1s by C1r, and binding and activation of downstream substrates C4 and C4b-bound C2 to initiate the reaction cascade.
  48. Hourcade D, Miesner D, Bee C, Zeldes W, Atkinson J. Duplication and divergence of the amino-terminal coding region of the complement receptor 1 (CR1) gene. An example of concerted (horizontal) evolution within a gene. J Biol Chem. 1990;265:974-80 pubmed
    Human C3b/C4b receptor or complement receptor type one (CR1) is one of a family of receptor and regulatory glycoproteins that are encoded at a single genetic region (1q32) and are composed largely of a tandemly repeated motif (short ..
  49. Rezende S, Simmonds R, Lane D. Coagulation, inflammation, and apoptosis: different roles for protein S and the protein S-C4b binding protein complex. Blood. 2004;103:1192-201 pubmed
    ..In human plasma, PS circulates approximately 40% as free PS (FPS) and 60% in complex with C4b-binding protein (C4BP)...
  50. Kotilainen H, Lokki M, Paakkanen R, Seppänen M, Tukiainen P, Meri S, et al. Complement C4 deficiency--a plausible risk factor for non-tuberculous mycobacteria (NTM) infection in apparently immunocompetent patients. PLoS ONE. 2014;9:e91450 pubmed publisher
    ..whether there was an association between NTM infections and deficiencies of complement components C4A or C4B that are encoded by major histocompatibility complex (MHC)...
  51. Breda L, Hsieh C, Castiblanco Valencia M, da Silva L, Barbosa A, Blom A, et al. Fine Mapping of the Interaction between C4b-Binding Protein and Outer Membrane Proteins LigA and LigB of Pathogenic Leptospira interrogans. PLoS Negl Trop Dis. 2015;9:e0004192 pubmed publisher
    ..are able to escape from complement activation by binding to host complement inhibitors Factor H [FH] and C4b-binding protein (C4BP) while non-pathogenic leptospires are rapidly killed in the presence of fresh serum...
  52. Castiblanco Valencia M, Fraga T, Breda L, Vasconcellos S, Figueira C, Picardeau M, et al. Acquisition of negative complement regulators by the saprophyte Leptospira biflexa expressing LigA or LigB confers enhanced survival in human serum. Immunol Lett. 2016;173:61-8 pubmed publisher
    ..proteins interact with the soluble complement regulators Factor H (FH), FH like-1 (FHL-1), FH related-1 (FHR-1) and C4b Binding Protein (C4BP). In this study, we used the saprophyte L...
  53. Morita N, Yamazaki T, Murakami Y, Fukui R, Yamai I, Ichimonji I, et al. C4b-binding protein negatively regulates TLR4/MD-2 response but not TLR3 response. FEBS Lett. 2017;591:1732-1741 pubmed publisher
    Recently, we reported a novel function for C4b-binding protein (C4BP) in inhibiting the toll-like receptor (TLR)1/2 response by interacting with TLR2...
  54. Moon K, Gorski J, Hugli T. Complete primary structure of human C4a anaphylatoxin. J Biol Chem. 1981;256:8685-92 pubmed
    ..cleaved between positions 77 and 78 by the protease C1s, a subcomponent of C1, generating the fragments C4a and C4b. Human C4a was isolated directly from fresh serum after C1 of the classical pathway of complement was activated by ..
  55. Lee H, Chang S, Tseng Y, Lee Y. Identification of the size and antigenic determinants of the human C4 gene by a polymerase chain-reaction-based amplification method. Anal Biochem. 2006;357:122-7 pubmed
    The human C4 complement components of the C4 locus are encoded by two genes, C4A and C4B, located on chromosome 6p21.3 of the major histocompatibility complex of the human leukocyte antigen class III region...
  56. Sekar A, Bialas A, de Rivera H, Davis A, Hammond T, Kamitaki N, et al. Schizophrenia risk from complex variation of complement component 4. Nature. 2016;530:177-83 pubmed publisher
    ..We found that these alleles generated widely varying levels of C4A and C4B expression in the brain, with each common C4 allele associating with schizophrenia in proportion to its tendency to ..
  57. Feng G, Li J, Zheng M, Yang Z, Liu Y, Zhang S, et al. Hepatitis B virus X protein up-regulates C4b-binding protein ? through activating transcription factor Sp1 in protection of hepatoma cells from complement attack. Oncotarget. 2016;7:28013-26 pubmed publisher
    ..Moreover, in this study we found that HBx protected hepatoma cells from complement attack by activation of C4b-binding protein ? (C4BP?), a potent inhibitor of complement system...
  58. Bos S, Phillips M, Watts G, Verhoeven A, Sijbrands E, Ward N. Novel protein biomarkers associated with coronary artery disease in statin-treated patients with familial hypercholesterolemia. J Clin Lipidol. 2017;11:682-693 pubmed publisher
    ..leucine-rich alpha-2-glycoprotein (LRG1), inter-alpha-trypsin inhibitor heavy chain H3, complement C4-B (C4B), complement C1q subcomponent subunit B (C1QB), monocyte differentiation antigen (CD14), and histidine-rich ..
  59. Neves M, Cotovio P, Machado S, Santos L, Macario F, Alves R, et al. C4d deposits in acute "cell-mediated" rejection: a marker for renal prognosis?. Transplant Proc. 2012;44:2360-5 pubmed publisher
    ..Graft loss occurred in 30.8% of C4d- patients versus 45.5% in C4d+ patients (P = NS). Our results suggest that detection of C4d staining in acute "cell-mediated" rejection does not imply a worse renal prognosis. ..
  60. Li J, An L, Zhang Z. Usefulness of complement activation products in Chinese patients with systemic lupus erythematosus. Clin Exp Rheumatol. 2014;32:48-53 pubmed
    ..001), low serum C4 (p=0.006), anti-dsDNA (IIF) (p=0.001), and anti-dsDNA (ELISA) (p=0.001). Complement activation products C3d and C4d binding to lymphocytes can reflect the disease activity of SLE and can be used as biomarkers for SLE. ..
  61. Thanei S, Vanhecke D, Trendelenburg M. Anti-C1q autoantibodies from systemic lupus erythematosus patients activate the complement system via both the classical and lectin pathways. Clin Immunol. 2015;160:180-7 pubmed publisher
    ..IgG anti-C1q resulted in the activation of the CP as reflected by C4b deposition in the presence of purified C1 and C4 in a dose-dependent manner...
  62. Campbell R, Gagnon J, Porter R. Amino acid sequence around the thiol and reactive acyl groups of human complement component C4. Biochem J. 1981;199:359-70 pubmed
    ..reactive acyl group and the free thiol group have been shown to reside in C4d, a fragment of the alpha'-chain of C4b derived from digestion of the molecule with the control proteins C3b inactivator and C4-binding protein...
  63. Bay J, Schejbel L, Madsen H, Sørensen S, Hansen J, Garred P. Low C4 gene copy numbers are associated with superior graft survival in patients transplanted with a deceased donor kidney. Kidney Int. 2013;84:562-9 pubmed publisher
    ..The C4 protein exists as two isotypes C4A and C4B encoded by the C4A and C4B genes, both of which are found with varying copy numbers...
  64. Xiang J, Li X, Chen Y, Lu Y, Yu M, Chen X, et al. Complement factor I from flatfish half-smooth tongue (Cynoglossus semilaevis) exhibited anti-microbial activities. Dev Comp Immunol. 2015;53:199-209 pubmed publisher
    ..substrate modulating cofactors (such as complement factor H, C4bp, CR1, etc), Cfi cleaves and inactivates C3b and C4b, thereby controlling the complement-mediated processes...
  65. Weinberger K, Collazo N, Aguillon J, Molina M, Rosas C, Peña J, et al. Triatoma infestans Calreticulin: Gene Cloning and Expression of a Main Domain That Interacts with the Host Complement System. Am J Trop Med Hyg. 2017;96:295-303 pubmed publisher
    ..it inhibits the classical pathway of complement, at its earliest stage of activation, namely the generation of C4b. Possibly, the presence of TiCRT in the salivary gland represents an evolutionary adaptation in hematophagous ..
  66. Prohaszka Z, Hidvegi T, Ujhelyi E, Stoiber H, Dierich M, Susal C, et al. Interaction of complement and specific antibodies with the external glycoprotein 120 of HIV-1. Immunology. 1995;85:184-9 pubmed
    ..antibodies were detected with specific, peroxidase-labelled antibodies against different complement proteins (C1q, C4b, C3b) and the gamma-chain of antibodies...
  67. Kjaer T, Thiel S, Andersen G. Toward a structure-based comprehension of the lectin pathway of complement. Mol Immunol. 2013;56:413-22 pubmed publisher
    ..These models are used to discuss cis- versus trans-activation of MASP proteases and the geometry of C4 deposition occurring on glycans in the lectin pathway. ..
  68. Guerra Junior G, Grumach A, de Lemos Marini S, Kirschfink M, Condino Neto A, de Araujo M, et al. Complement 4 phenotypes and genotypes in Brazilian patients with classical 21-hydroxylase deficiency. Clin Exp Immunol. 2009;155:182-8 pubmed publisher
    ..Low C4A or C4B correlated well with RCCX mono-modular gene organization, but no association between C4 haplotypes and recurrent ..
  69. Blasko B, Kolka R, Thorbjornsdottir P, Sigurdarson S, Sigurdsson G, Ronai Z, et al. Low complement C4B gene copy number predicts short-term mortality after acute myocardial infarction. Int Immunol. 2008;20:31-7 pubmed
    ..Previously, we found that the C4B*Q0 genotype (low copy number of the C4B gene that encodes the fourth component of complement) is strongly ..
  70. Kisserli A, Tabary T, Cohen J, Duret V, Mahmoudi R. High-resolution Melting PCR for Complement Receptor 1 Length Polymorphism Genotyping: An Innovative Tool for Alzheimer's Disease Gene Susceptibility Assessment. J Vis Exp. 2017;: pubmed publisher
    ..As a receptor for the complement components C3b and C4b, CR1 regulates the activation of the complement cascade and promotes the phagocytosis of immune complexes and ..
  71. Aoki H, Takizawa F, Tsuji S, Nagasawa S. Elongation factor-1alpha as a homologous complement activator of Jurkat cells. Int J Mol Med. 2000;6:87-92 pubmed
    ..The homologous complement activation did not proceed with EGTA-serum. In addition, C4b, a fragment produced by activation of the classical or lectin pathways was found to bind with EF-1alpha...
  72. Carroll M, Campbell R, Bentley D, Porter R. A molecular map of the human major histocompatibility complex class III region linking complement genes C4, C2 and factor B. Nature. 1984;307:237-41 pubmed
    ..The C2 and factor B genes, less than 2 kb apart, are about 30 kb from two C4 genes separated from each other by about 10 kb. ..
  73. Takeda Y, Kaneda K, Jimma F, Shiobara N, Saniabadi A, Wakabayashi I. Suppression of Th1 cytokine production by a peptide derived from C4b. Inflamm Res. 2013;62:951-9 pubmed publisher
    ..We recently reported that monomeric C4b inhibits CXCL10 production from blood cells...
  74. Zorzetto M, Datturi F, Divizia L, Pistono C, Campo I, De Silvestri A, et al. Complement C4A and C4B Gene Copy Number Study in Alzheimer's Disease Patients. Curr Alzheimer Res. 2017;14:303-308 pubmed publisher
    ..This protein has two isoforms, encoded by two genes: C4A and C4B localized to the HLA class III region...
  75. Avirutnan P, Hauhart R, Somnuke P, Blom A, Diamond M, Atkinson J. Binding of flavivirus nonstructural protein NS1 to C4b binding protein modulates complement activation. J Immunol. 2011;187:424-33 pubmed publisher
    ..flavivirus NS1 in limiting complement activation by forming a complex with C1s and C4 to promote cleavage of C4 to C4b. In this study, we demonstrate a second mechanism, also involving C4 and its active fragment C4b, by which NS1 ..
  76. Chen J, Wu Y, Mok M, Wu Y, Lintner K, Wang C, et al. Effects of Complement C4 Gene Copy Number Variations, Size Dichotomy, and C4A Deficiency on Genetic Risk and Clinical Presentation of Systemic Lupus Erythematosus in East Asian Populations. Arthritis Rheumatol. 2016;68:1442-1453 pubmed publisher
    ..with C4A deficiency were found to have a recombinant haplotype with bimodular C4-Long and C4-Short genes, encoding C4B1 and C4B96, which was linked to HLA-DRB1*1501. DNA sequencing revealed an E920K polymorphism in C4B96...
  77. Blasko B, Bánlaki Z, Gyapay G, Pozsonyi E, Sasvari Szekely M, Rajczy K, et al. Linkage analysis of the C4A/C4B copy number variation and polymorphisms of the adjacent steroid 21-hydroxylase gene in a healthy population. Mol Immunol. 2009;46:2623-9 pubmed publisher
    Genes encoding the steroid 21-hydroxylase (CYP21A2) and the complement component C4 proteins (C4A and C4B) are located in the MHC region in a strongly linked structure named RCCX module...
  78. Hein E, Honore C, Skjoedt M, Munthe Fog L, Hummelshøj T, Garred P. Functional analysis of Ficolin-3 mediated complement activation. PLoS ONE. 2010;5:e15443 pubmed publisher
    ..The assay provides the possibility to diagnose functional and genetic defects of Ficolin-3 and down stream components in the lectin complement pathway. ..
  79. Norman P, Norberg S, Guethlein L, Nemat Gorgani N, Royce T, Wroblewski E, et al. Sequences of 95 human MHC haplotypes reveal extreme coding variation in genes other than highly polymorphic HLA class I and II. Genome Res. 2017;27:813-823 pubmed publisher
    ..i>HLA class I and HLA class II genes and the complex structural diversity of complement factor C4A/C4B It has also uncovered extensive and unexpected diversity in other MHC genes; an example is MUC22, ..
  80. Rawal N, Pangburn M. Formation of high affinity C5 convertase of the classical pathway of complement. J Biol Chem. 2003;278:38476-83 pubmed
    ..Kinetic parameters revealed that the soluble form of the enzyme (C4b,C2a) cleaved C5 at a catalytic rate similar to that of the surface-bound form (EAC1,C4b,C2a)...
  81. Gierej B, Kobryń K, Gierej P, Gornicka B. C4d in acute rejection after liver transplantation and its usefulness in differential diagnosis between acute liver rejection and hepatitis C recurrence. Ann Transplant. 2014;19:373-81 pubmed publisher
    ..Our results suggest that C4d deposits are insufficient in differentiation between both examined liver pathologies, but could be a useful marker in the diagnostics of acute liver rejection with humoral component. ..
  82. Kask L, Trouw L, Dahlback B, Blom A. The C4b-binding protein-protein S complex inhibits the phagocytosis of apoptotic cells. J Biol Chem. 2004;279:23869-73 pubmed
    ..We have examined a role of the major soluble inhibitor of the classic and lectin complement pathways, C4b-binding protein (C4BP), in the clearance of apoptotic cells...
  83. Ulgiati D, Townend D, Christiansen F, Dawkins R, Abraham L. Complete sequence of the complement C4 gene from the HLA-A1, B8, C4AQ0, C4B1, DR3 haplotype. Immunogenetics. 1996;43:250-2 pubmed
  84. Li S, Liu Z, Zen C, Wang Q, Wang Y, Li L. Peritubular capillary C4d deposition in lupus nephritis different from antibody-mediated renal rejection. Lupus. 2007;16:875-80 pubmed
  85. Nakao A, Miyazaki N, Ohira K, Hagihara H, Takagi T, Usuda N, et al. Immature morphological properties in subcellular-scale structures in the dentate gyrus of Schnurri-2 knockout mice: a model for schizophrenia and intellectual disability. Mol Brain. 2017;10:60 pubmed publisher
    ..In the mutants' brains, there are increases in C4b and C1q genes, which are considered to mediate synapse elimination during postnatal development...
  86. Gilliam B, Wolff A, Moore T. Partial C4 deficiency in juvenile idiopathic arthritis patients. J Clin Rheumatol. 2007;13:256-60 pubmed
    ..C4A deficiencies have been associated with autoimmune disease and C4B with increased frequency of infection...
  87. Nissilä E, Korpela K, Lokki A, Paakkanen R, Jokiranta S, de Vos W, et al. C4B gene influences intestinal microbiota through complement activation in patients with paediatric-onset inflammatory bowel disease. Clin Exp Immunol. 2017;190:394-405 pubmed publisher
    ..We examined the influence of C4B gene number on intestinal microbiota and in-vitro serum complement activation by intestinal microbes in PIBD ..
  88. Hofer J, Forster F, Isenman D, Wahrmann M, Leitner J, Hölzl M, et al. Ig-like transcript 4 as a cellular receptor for soluble complement fragment C4d. FASEB J. 2016;30:1492-503 pubmed publisher
    ..Both receptors, expressed on monocytes, macrophages, and dendritic cells, also interacted with the CSPs C3d, C4b, C3b, and iC3b. However, C4d did not bind to classic complement receptors (CRs)...
  89. Heeb M, Koenen R, Fernandez J, Hackeng T. Direct anticoagulant activity of protein S-C4b binding protein complex in Heerlen heterozygotes and normals. J Thromb Haemost. 2004;2:1766-73 pubmed
    Plasma protein S normally circulates free (40%) or complexed with C4b-binding protein (PS-C4BP); only free protein S is a cofactor for activated protein C during factor (F) Va inactivation...
  90. Lorho R, Turlin B, Aqodad N, Triki N, de Lajarte Thirouard A, Camus C, et al. C4d: a marker for hepatic transplant rejection. Transplant Proc. 2006;38:2333-4 pubmed
    ..These results, which are comparable to recently published data, give credence to the theory that C4d could be used as a marker for rejection following hepatic transplantation. ..
  91. Buurma A, Cohen D, Veraar K, Schonkeren D, Claas F, Bruijn J, et al. Preeclampsia is characterized by placental complement dysregulation. Hypertension. 2012;60:1332-7 pubmed publisher
    ..Inhibiting excessive complement activation may be a promising therapeutic approach in the management of preeclampsia. ..
  92. Blom A, Webb J, Villoutreix B, Dahlback B. A cluster of positively charged amino acids in the C4BP alpha-chain is crucial for C4b binding and factor I cofactor function. J Biol Chem. 1999;274:19237-45 pubmed
    b>C4b-binding protein (C4BP) is a regulator of the classical complement pathway, acting as a cofactor to factor I in the degradation of C4b...