C4A

Summary

Gene Symbol: C4A
Description: complement C4A (Rodgers blood group)
Alias: C4A2, C4A3, C4A4, C4A6, C4AD, C4S, CO4, CPAMD2, complement C4-A, C3 and PZP-like alpha-2-macroglobulin domain-containing protein 2, C4A anaphylatoxin, MHC class III region complement, Rodgers form of C4, acidic C4, acidic complement C4, complement component 4A (Rodgers blood group)
Species: human
Products:     C4A

Top Publications

  1. 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
    ..Among C4-deficient patients (n = 66, 52.8% 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...
  2. Rupert K, Moulds J, Yang Y, Arnett F, Warren R, Reveille J, et al. The molecular basis of complete complement C4A and C4B deficiencies in a systemic lupus erythematosus patient with homozygous C4A and C4B mutant genes. J Immunol. 2002;169:1570-8 pubmed
    ..Immunochemical experiments showed that the patient and his sibling had complete absence of C4A and C4B proteins and were negative for the Rodgers and Chido blood group Ags...
  3. Lokki M, Circolo A, Ahokas P, Rupert K, Yu C, Colten H. Deficiency of human complement protein C4 due to identical frameshift mutations in the C4A and C4B genes. J Immunol. 1999;162:3687-93 pubmed
    The complement protein C4, encoded by two genes (C4A and C4B) on chromosome 6p, is the most polymorphic among the MHC III gene products...
  4. Saxena K, Kitzmiller K, Wu Y, Zhou B, Esack N, Hiremath L, et al. Great genotypic and phenotypic diversities associated with copy-number variations of complement C4 and RP-C4-CYP21-TNX (RCCX) modules: a comparison of Asian-Indian and European American populations. Mol Immunol. 2009;46:1289-303 pubmed publisher
    ..The medium gene copy-numbers for C4 and its isotypes, acidic C4A and basic C4B, were 4, 2 and 2, respectively, but their frequencies were only 53-56%...
  5. Kainulainen L, Peltola V, Seppanen M, Viander M, He Q, Lokki M, et al. C4A deficiency in children and adolescents with recurrent respiratory infections. Hum Immunol. 2012;73:498-501 pubmed publisher
    ..of complement factor C4 in the defense against respiratory infections, we studied complement factor C4 allotypes C4A and C4B and copy numbers of C4A and C4B genes in 84 children and young adults with recurrent acute otitis media, ..
  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
    ..of complement 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. 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...
  8. 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 ..
  9. 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
    ..The 2 bp insertion in exon 29, which was previously identified in non-Chinese populations and caused defective C4A genes, was directly typed by sequencing the whole exon 29 using exon specific primers...

More Information

Publications104 found, 100 shown here

  1. 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 ..
  2. 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...
  3. Sullivan K, Kim N, Goldman D, Petri M. C4A deficiency due to a 2 bp insertion is increased in patients with systemic lupus erythematosus. J Rheumatol. 1999;26:2144-7 pubmed
    The association of C4A deficiency with systemic lupus erythematosus (SLE) is well documented...
  4. 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 ..
  5. 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...
  6. 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...
  7. Barba G, Rittner C, Schneider P. Genetic basis of human complement C4A deficiency. Detection of a point mutation leading to nonexpression. J Clin Invest. 1993;91:1681-6 pubmed
    The fourth component of the human complement system (C4) is coded for by two genes, C4A and C4B, located within the MHC. Null alleles of C4 (C4Q0) are defined by the absence of C4 protein in plasma...
  8. Banerjee A, Mazumdar B, Meyer K, Di Bisceglie A, Ray R, Ray R. Transcriptional repression of C4 complement by hepatitis C virus proteins. J Virol. 2011;85:4157-66 pubmed publisher
    ..Further, C4 mRNA levels of the two isoforms (C4A and C4B) were significantly reduced in hepatocytes transfected with RNA from HCV genotype 1a or 2a...
  9. 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. ..
  10. 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)...
  11. 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. ..
  12. 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
    ..b>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...
  13. 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
    ..PRT) in association with two restriction enzyme digest variant ratio tests (REDVRs) to determine total C4 GCN, C4A GCN, and C4B GCN...
  14. Sárközy M, Szűcs G, Pipicz M, Zvara Ã, Éder K, Fekete V, et al. The effect of a preparation of minerals, vitamins and trace elements on the cardiac gene expression pattern in male diabetic rats. Cardiovasc Diabetol. 2015;14:85 pubmed publisher
    ..Our results and further studies exploring the mechanistic role of individual genes may contribute to the prevention or diagnosis of cardiac complications in diabetes. ..
  15. Perera N, Godahewa G, Jung S, Kim M, Nam B, Lee J. Identification and characterization of a carboxypeptidase N1 from red lip mullet (Liza haematocheila); revealing its immune relevance. Fish Shellfish Immunol. 2019;84:223-232 pubmed publisher
    ..un-transfected controls suggesting that MuCPN1 is an active protease which releases arginine from complement C3a, C4a, and C5a...
  16. Sárközy M, Szucs G, Fekete V, Pipicz M, Eder K, Gáspár R, et al. Transcriptomic alterations in the heart of non-obese type 2 diabetic Goto-Kakizaki rats. Cardiovasc Diabetol. 2016;15:110 pubmed publisher
    ..g. Tnni1, Mylk2, Col8a1, Adam33), cell growth and differentiation (e.g. Gpc3, Jund), immune response (e.g. C3, C4a), and others (e.g. Lrp8, Msln, Klkc1, Epn3)...
  17. Lodovicho M, Costa T, Bernardes C, Menaldo D, Zoccal K, Carone S, et al. Investigating possible biological targets of Bj-CRP, the first cysteine-rich secretory protein (CRISP) isolated from Bothrops jararaca snake venom. Toxicol Lett. 2017;265:156-169 pubmed publisher
    ..and acting directly on important components (C3 and C4), thus inducing the generation of anaphylatoxins (C3a, C4a and C5a)...
  18. Catucci G, Zgrablic I, Lanciani F, Valetti F, Minerdi D, Ballou D, et al. Characterization of a new Baeyer-Villiger monooxygenase and conversion to a solely N-or S-oxidizing enzyme by a single R292 mutation. Biochim Biophys Acta. 2016;1864:1177-1187 pubmed publisher
    ..on the wild type enzyme using stopped-flow spectroscopy allowed for the detection of the characteristic oxygenating C4a-(hydro)peroxyflavin intermediate, which decayed rapidly in the presence of the substrate...
  19. Binda C, Robinson R, Martín Del Campo J, Keul N, Rodríguez P, Robinson H, et al. An unprecedented NADPH domain conformation in lysine monooxygenase NbtG provides insights into uncoupling of oxygen consumption from substrate hydroxylation. J Biol Chem. 2015;290:12676-88 pubmed publisher
    ..may explain the biochemical properties of NbtG, specifically with regard to the substantial uncoupling and limited stabilization of the C4a-hydroperoxyflavin intermediate. Biological implications of these findings are discussed.
  20. Escamilla Rivera V, Solorio Rodríguez A, Uribe Ramírez M, Lozano O, Lucas S, Chagolla López A, et al. Plasma protein adsorption on Fe3O4-PEG nanoparticles activates the complement system and induces an inflammatory response. Int J Nanomedicine. 2019;14:2055-2067 pubmed publisher
    ..Furthermore, IONP-PEG activated in vitro, the complement system and induced a substantial increment of C3a and C4a anaphylatoxins while IONP-bare and IONP-PVP did not...
  21. Wen J, Doerner J, Weidenheim K, Xia Y, Stock A, Michaelson J, et al. TNF-like weak inducer of apoptosis promotes blood brain barrier disruption and increases neuronal cell death in MRL/lpr mice. J Autoimmun. 2015;60:40-50 pubmed publisher
    ..Furthermore, MRL/lpr Fn14KO mice displayed reduced antibody (IgG) and complement (C3, C6, and C4a) deposition in the brain...
  22. Thomas K, Valenzuela N, Gjertson D, Mulder A, Fishbein M, Parry G, et al. An Anti-C1s Monoclonal, TNT003, Inhibits Complement Activation Induced by Antibodies Against HLA. Am J Transplant. 2015;15:2037-49 pubmed publisher
    ..TNT003 inhibited HLA-Ab mediated complement deposition on HAEC in a concentration-dependent manner; C3a, C4a and C5a anaphylatoxin production was also diminished by TNT003...
  23. He X, Yin W, Ding Y, Cui S, Luan J, Zhao P, et al. Higher Serum Angiotensinogen Is an Indicator of IgA Vasculitis with Nephritis Revealed by Comparative Proteomes Analysis. PLoS ONE. 2015;10:e0130536 pubmed publisher
    ..A few differentially abundant proteins identified, such as C4a, serum amyloid A, angiotensinogen, and kininogen 1, were further validated by ELISA...
  24. 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)...
  25. El Kashef N, Gomes I, Mercer Chalmers Bender K, Schneider P, Rothschild M, Juebner M. Comparative proteome analysis for identification of differentially abundant proteins in SIDS. Int J Legal Med. 2017;131:1597-1613 pubmed publisher
    ..demonstrated by exploring some candidate proteins especially APOA1, GAPDH, S100B, zyxin, and complement component C4A. According to the results of this study, these proteins might be used as diagnostic biomarkers for SIDS...
  26. Kim H, Hyeon J, Hwang S, Lee Y, Lee S, Yoo J, et al. Epidemiology and virologic investigation of human enterovirus 71 infection in the Republic of Korea from 2007 to 2012: a nationwide cross-sectional study. BMC Infect Dis. 2016;16:425 pubmed publisher
    ..The major subgenotype of EV71 isolates circulating in ROK was the C4a strain, which has also appeared in China, Japan and Vietnam...
  27. Lee S, Kim N, Lee M, Jo Y, Bae J, Hyun M, et al. A discrete {Co4(μ3-OH)4}(4+) cluster with an oxygen-rich coordination environment as a catalyst for the epoxidation of various olefins. Dalton Trans. 2016;45:1727-36 pubmed publisher
    Using the sterically hindered terphenyl-based carboxylate, the tetrameric Co(ii) complex [Co4(μ3-OH)4(μ-O2CAr(4F-Ph))2(μ-OTf)2(Py)4] () with an asymmetric cubane-type core has been synthesized and fully characterized by X-ray ..
  28. 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
  29. Anderson M, Milner C, Cotton R, Campbell R. The coding sequence of the hemolytically inactive C4A6 allotype of human complement component C4 reveals that a single arginine to tryptophan substitution at beta-chain residue 458 is the likely cause of the defect. J Immunol. 1992;148:2795-802 pubmed
    The C4A6 allotype of the human complement component C4 is known to be defective in C5 binding within the C5 convertase...
  30. Lattimer C, Azzam M, Kalodiki E, Geroulakos G. Quantifying saphenous recirculation in patients with primary lower extremity venous reflux. J Vasc Surg Venous Lymphat Disord. 2016;4:179-86 pubmed publisher
    ..The clinical, etiological, anatomical, pathophysiological class was C2 = 3, C3 = 2, C4a = 6, C4b = 4, C5 = 1...
  31. Tatikolov А, Akimkin T, Panova I, Yarmoluk S. Spectral-fluorescent study of the interaction of the polymethine dye probe Cyan 2 with chondroitin-4-sulfate. Spectrochim Acta A Mol Biomol Spectrosc. 2017;177:93-96 pubmed publisher
    ..of the polymethine dye probe 3,3',9-trimethylthiacarbocyanine iodide (Cyan 2) with chondroitin-4-sulfate (C4S) in buffer solutions with different pH and in water in the absence of buffers has been studied by spectral-..
  32. Pimviriyakul P, Thotsaporn K, Sucharitakul J, Chaiyen P. Kinetic Mechanism of the Dechlorinating Flavin-dependent Monooxygenase HadA. J Biol Chem. 2017;292:4818-4832 pubmed publisher
    ..Stopped-flow and rapid-quench flow experiments of HadA with 4-CP show the involvement of specific intermediates (C4a-hydroperoxy-FAD and C4a-hydroxy-FAD) in the reaction, define rate constants and the order of substrate binding, and ..
  33. Rawal N, Pangburn M. Formation of high affinity C5 convertase of the classical pathway of complement. J Biol Chem. 2003;278:38476-83 pubmed
  34. Gilliam B, Wolff A, Moore T. Partial C4 deficiency in juvenile idiopathic arthritis patients. J Clin Rheumatol. 2007;13:256-60 pubmed
    ..b>C4A deficiencies have been associated with autoimmune disease and C4B with increased frequency of infection...
  35. Lattimer C, Mendoza E. Superficial venous reflux duration and cessation with two concurrent duplex probes. J Vasc Surg Venous Lymphat Disord. 2015;3:154-60 pubmed publisher
    ..of the Clinical, Etiologic, Anatomic, and Pathophysiologic (CEAP) classification was as follows: C2, 6; C3, 4; C4a, 5; and C4b, 2. After 2 minutes of elevation, the leg was assessed for reflux duration with duplex ultrasound...
  36. Caby F. CD4+/CD8+ ratio restoration in long-term treated HIV-1-infected individuals. AIDS. 2017;31:1685-1695 pubmed publisher
    ..Study cohort based on the French Hospital Database on HIV (ANRS CO4)...
  37. Stefansson Thors V, Kolka R, Sigurdardottir S, Edvardsson V, Arason G, Haraldsson A. Increased frequency of C4B*Q0 alleles in patients with Henoch-Schönlein purpura. Scand J Immunol. 2005;61:274-8 pubmed
    ..Serum levels of immunoglobulin A, C4A, C4B and mannan-binding lectin were measured and compared between the two groups...
  38. Du S, Yu T, Liao W, Hu C. Structure modeling, synthesis and X-ray diffraction determination of an extra-large calixarene-based coordination cage and its application in drug delivery. Dalton Trans. 2015;44:14394-402 pubmed publisher
    An extra-large octahedral coordination cage (CIAC-114) was designed and modeled based on Co4-p-tert-butylsulfonylcalix[4]arene (Co4-(SC4A-SO2)) subunits and 4,4',4''-(benzene-1,3,5-triyl-tris(benzene-4,1-diyl))tribenzoate (BBB) ligands ..
  39. Pereira K, Faria A, Liphaus B, Jesus A, Silva C, Carneiro Sampaio M, et al. Low C4, C4A and C4B gene copy numbers are stronger risk factors for juvenile-onset than for adult-onset systemic lupus erythematosus. Rheumatology (Oxford). 2016;55:869-73 pubmed publisher
    ..C4 is encoded by two different genes, C4A and C4B, which show considerable gene copy number (GCN) variation...
  40. Mortensen S, Jensen J, Andersen G. Solution Structures of Complement C2 and Its C4 Complexes Propose Pathway-specific Mechanisms for Control and Activation of the Complement Proconvertases. J Biol Chem. 2016;291:16494-507 pubmed publisher
  41. Rani A, Dhillon A, Sharma K, Goyal A. Insights into the structural characteristics and substrate binding analysis of chondroitin AC lyase (PsPL8A) from Pedobacter saltans. Int J Biol Macromol. 2018;109:980-991 pubmed publisher
    ..Isothermal titration calorimetry analysis of Y212F and H203A with C4S polysaccharide, showed moderate binding by Y212F (Ka=9.56±3...
  42. Shen L, Wu L, Sanlioglu S, Chen R, Mendoza A, Dangel A, et al. Structure and genetics of the partially duplicated gene RP located immediately upstream of the complement C4A and the C4B genes in the HLA class III region. Molecular cloning, exon-intron structure, composite retroposon, and breakpoint of gene duplic. J Biol Chem. 1994;269:8466-76 pubmed
    ..and characterized a pair of partially duplicated genes, RP1 and RP2, located 611 base pairs upstream of the human C4A and C4B genes, respectively...
  43. Cisło M, Hałasa J, Wasik F, Nockowski P, Prussak M, Manczak M, et al. Allelic distribution of complement components BF, C4A, C4B, and C3 in Psoriasis vulgaris. Immunol Lett. 2002;80:145-9 pubmed
    ..Therefore, we typed 67 psoriatic patients for alleles of the HLA-linked complement components BF, C4A and C4B. Alleles of C3, encoded on another chromosome, were established in parallel as a negative control...
  44. Tandon M, Perez P, Burbelo P, Calkins C, Alevizos I. Laser microdissection coupled with RNA-seq reveal cell-type and disease-specific markers in the salivary gland of Sjögren's syndrome patients. Clin Exp Rheumatol. 2017;35:777-785 pubmed
    ..Up-regulated genes in the SS ductal cells included C4A complement and the SLC26A9 ion channel...
  45. Tsai L, Hsiao S, Tsai L, Lin C, Tsai J, Liou D, et al. The sodium-dependent glucose cotransporter SLC5A11 as an autoimmune modifier gene in SLE. Tissue Antigens. 2008;71:114-26 pubmed
    ..Furthermore, SLC5A11 might induce apoptosis through the TNF-alpha, PDCD1 pathway. The present genotype-phenotype mapping approach should be applicable to genetic study of other complex diseases. ..
  46. Li X, Clatworthy E, Masters A, Maschmeyer T. Molecular Cobalt Clusters as Precursors of Distinct Active Species in Electrochemical, Photochemical, and Photoelectrochemical Water Oxidation Reactions in Phosphate Electrolytes. Chemistry. 2015;21:16578-84 pubmed publisher
    Three cobalt model molecular compounds, Co-cubane ([Co4 (µ3 -O)4 (µ-OAc)4 py4 ]), Co-trimer ([Co3 (μ3 -O)(µ-OAc)6 py3 ]PF6 ), and Co-dimer ([Co2 (μ-OH)2 (µ-OAc)(OAc)2 py4 ]PF6 ), are investigated as water oxidation ..
  47. Inokuchi Y, Hirai K, Ebata T. Electronic structure and conformational conversion of calix[4]arene complexes with alkali metal ions. Phys Chem Chem Phys. 2017;19:12857-12867 pubmed publisher
    The ultraviolet photodissociation (UVPD) spectra of calix[4]arene (C4A) complexes with alkali metal ions, M+·C4A (M = Na, K, Rb, and Cs), are measured in the 34?000-37?000 cm-1 region under cold (?10 K) conditions ..
  48. Sobrado P, Tanner J. Multiple functionalities of reduced flavin in the non-redox reaction catalyzed by UDP-galactopyranose mutase. Arch Biochem Biophys. 2017;632:59-65 pubmed publisher
    ..The major hot spots of reactivity include the N5, C4a, and C4O atoms of the isoalloxazine, and the 2' hydroxyl of the ribityl chain...
  49. 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
    ..Complement C4A and C4B gene numbers were determined by genomic reverse transcription-polymerase chain reaction (RT-PCR) from 64 ..
  50. Sobue Y, Kojima T, Kurokouchi K, Takahashi S, Yoshida H, Poole R, et al. Prediction of progression of damage to articular cartilage 2 years after anterior cruciate ligament reconstruction: use of aggrecan and type II collagen biomarkers in a retrospective observational study. Arthritis Res Ther. 2017;19:265 pubmed publisher
    ..of type II collagen (C2C) and proteoglycan glycosaminoglycans keratan sulfate (KS), chondroitin-4-sulfate (?di-C4S), and chondroitin-6-sulfate (?di-C6S) were measured at ACL reconstruction...
  51. Chakravarti D, Campbell R, Gagnon J. Amino acid sequence of a polymorphic segment from fragment C4d of human complement component C4. FEBS Lett. 1983;154:387-90 pubmed
    ..and Porter, R.R. (1983) Proc. Natl. Acad. Sci. USA 80, in press] alanine or serine are found at position 98. These results may in part help to explain the inherited variants of human C4 seen on gel electrophoresis. ..
  52. Fujita T, Matsushita M, Endo Y. The lectin-complement pathway--its role in innate immunity and evolution. Immunol Rev. 2004;198:185-202 pubmed
    ..Based on these findings, it seems likely that the complement system played a pivotal role in innate immunity before the evolution of an acquired immune system in jawed vertebrates. ..
  53. Li J, Ge X, Wang X, Liu X, Ma J. Complement System in the Pathogenesis of Benign Lymphoepithelial Lesions of the Lacrimal Gland. PLoS ONE. 2016;11:e0148290 pubmed publisher
    ..system-related genes in the pathologic tissue, including C2, C3, ITGB2, CR2, C1QB, CR1, ITGAX, CFP, C1QA, C4B|C4A, FANCA, C1QC, C3AR1 and CFHR4, were significantly upregulated while 7 other complement system-related genes, C5, ..
  54. Wu J, Liu M, Gao K, Fan Y, Guo X, Meng X, et al. Co-Cluster-Based Metal-Organic Frameworks as Selective Catalysts for Benzene Tandem Acylation-Nazarov Cyclization to Benzocyclopentanone. Chemistry. 2017;: pubmed publisher
    ..Herein, we reported that two metal-cluster-based metal-organic frameworks (MCOFs) {(H3O)2[Co4(pbcd)2(?3-OH)2]·(CH3CH2OH)·4H2O}n (1) and {[Co5.25(mcd)2(HCO2)(?2-O)0.5(?3-OH)0...
  55. Kusayama Y, Akamatsu Y, Kumagai K, Kobayashi H, Aratake M, Saito T. Changes in synovial fluid biomarkers and clinical efficacy of intra-articular injections of hyaluronic acid for patients with knee osteoarthritis. J Exp Orthop. 2014;1:16 pubmed publisher
    ..The SF total volume, viscosity, and levels of HA, chondroitin 4-sulfate (C4S), chondroitin 6-sulfate (C6S), keratin sulfate, and interleukin (IL)-6 were measured before the first and fifth ..
  56. Veszeli N, Kőhalmi K, Kajdacsi E, Gulyás D, Temesszentandrási G, Cervenak L, et al. Complete kinetic follow-up of symptoms and complement parameters during a hereditary angioedema attack. Allergy. 2017;: pubmed publisher
    ..C1-INH concentration and functional activity (C1-INHc+f ), C1(q,r,s), C3, C4, C3a, C4a, C5a, and SC5b-9 levels were measured in blood samples obtained during the 96-hour observation period...
  57. Harrison R, Thomas M, Tack B. Sequence determination of the thiolester site of the fourth component of human complement. Proc Natl Acad Sci U S A. 1981;78:7388-92 pubmed
    ..Further comparisons among these three proteins have indicated additional homologies on both the NH2- and COOH-terminal sides of the thiolester site. ..
  58. Hamad O, Nilsson P, Wouters D, Lambris J, Ekdahl K, Nilsson B. Complement component C3 binds to activated normal platelets without preceding proteolytic activation and promotes binding to complement receptor 1. J Immunol. 2010;184:2686-92 pubmed publisher
    ..However, the generation of C3(H(2)O) represents nonproteolytic activation of C3 and after factor I cleavage may act as a ligand for receptor binding. ..
  59. Liu Y, Wan L, Chang C, Liao W, Chen W, Tsai Y, et al. Association between copy number variation of complement component C4 and Graves' disease. J Biomed Sci. 2011;18:71 pubmed publisher
    ..A case-control study including 624 patients with GD and 160 healthy individuals were enrolled. CNV of C4 isotypes (C4A and C4B) genes were performed by quantitative real-time polymerase chain reaction analysis...
  60. Nocturne G, Seror R, Fogel O, Belkhir R, Boudaoud S, Saraux A, et al. CXCL13 and CCL11 Serum Levels and Lymphoma and Disease Activity in Primary Sjögren's Syndrome. Arthritis Rheumatol. 2015;67:3226-33 pubmed publisher
    ..These findings demonstrate a link between CXCL13 and CCL11 and disease activity and lymphoma. This highlights the continuum between chronic B cell activation, disease activity, and lymphomagenesis in patients with primary SS. ..
  61. Tee M, Babalola G, Aza Blanc P, Speek M, Gitelman S, Miller W. A promoter within intron 35 of the human C4A gene initiates abundant adrenal-specific transcription of a 1 kb RNA: location of a cryptic CYP21 promoter element?. Hum Mol Genet. 1995;4:2109-16 pubmed
    Complement component C4 is encoded by two nearly identical genes, C4A and C4B, that encode a C4 precursor that is proteolytically cleaved into the alpha, beta and gamma subunits of the mature protein...
  62. Zhang H, Zhang Y, Yang F, Li L, Liu S, Xu Z, et al. Complement component C4A and apolipoprotein A-I in plasmas as biomarkers of the severe, early-onset preeclampsia. Mol Biosyst. 2011;7:2470-9 pubmed publisher
    ..The expression of complement component C4A and apolipoprotein A-I were validated by immunoblotting...
  63. Belt K, Carroll M, Porter R. The structural basis of the multiple forms of human complement component C4. Cell. 1984;36:907-14 pubmed
    cDNA clones of human complement components C4A and C4B alleles were prepared from mRNA obtained from the liver of a donor heterozygous at both loci...
  64. Sargent C, Anderson M, Hsieh S, Kendall E, Gomez Escobar N, Campbell R. Characterisation of the novel gene G11 lying adjacent to the complement C4A gene in the human major histocompatibility complex. Hum Mol Genet. 1994;3:481-8 pubmed
    ..The common arrangement of these genes is tel-C2-Bf-RD-G11-C4A-[P450c21A-YA-XA]-C4B-[P450c21B-YB ]-+ ++TNX-cen...
  65. Dahlman I, Elsen M, Tennagels N, Korn M, Brockmann B, Sell H, et al. Functional annotation of the human fat cell secretome. Arch Physiol Biochem. 2012;118:84-91 pubmed publisher
    ..Furthermore, many adipokines were extracellular matrix proteins. Several novel adipokines have potential important functional features warranting in depth analysis. ..
  66. Palsdottir A, Cross S, Edwards J, Carroll M. Correlation between a DNA restriction fragment length polymorphism and C4A6 protein. Nature. 1983;306:615-6 pubmed
    ..7 and 3.8 kilobase (kb) BglII restriction fragments in each of 9 unrelated individuals with a C4A6 allele, and in none of 22 unrelated individuals in whom this allele was not expressed...
  67. Grabar S, Selinger Leneman H, Abgrall S, Pialoux G, Weiss L, Costagliola D. Loss of long-term non-progressor and HIV controller status over time in the French Hospital Database on HIV - ANRS CO4. PLoS ONE. 2017;12:e0184441 pubmed publisher
    We studied the frequency and risk factors for loss of long-term non-progressor (LTNP) and HIV controller (HIC) status among patients identified as such in 2005 in the French Hospital Database on HIV (FHDH-ANRS CO4).
  68. Jüptner M, Flachsbart F, Caliebe A, Lieb W, Schreiber S, Zeuner R, et al. Low copy numbers of complement C4 and homozygous deficiency of C4A may predispose to severe disease and earlier disease onset in patients with systemic lupus erythematosus. Lupus. 2017;:961203317735187 pubmed publisher
    ..Results Homozygous deficiency of the C4A isotype was identified as the strongest risk factor for SLE (odds ratio (OR)?=?5.329; p?=?7...
  69. Yu C. Molecular genetics of the human MHC complement gene cluster. Exp Clin Immunogenet. 1998;15:213-30 pubmed
    ..One, two or three C4 genes may be present in a human MCGC haplotype and these genes may code for C4A, C4B, or both...
  70. Lv Y, He S, Zhang Z, Li Y, Hu D, Zhu K, et al. Confirmation of C4 gene copy number variation and the association with systemic lupus erythematosus in Chinese Han population. Rheumatol Int. 2012;32:3047-53 pubmed
    ..Furthermore, we found the association between C4A GCN and disease subphenotypes of arthritis with SLE...
  71. Kidmose R, Laursen N, Dobó J, Kjaer T, Sirotkina S, Yatime L, et al. Structural basis for activation of the complement system by component C4 cleavage. Proc Natl Acad Sci U S A. 2012;109:15425-30 pubmed
    ..Our results provide a unified structural framework for understanding the early and essential step of C4 cleavage in the elimination of pathogens and altered self through two major pathways of complement activation. ..
  72. Moon K, Gorski J, Hugli T. Complete primary structure of human C4a anaphylatoxin. J Biol Chem. 1981;256:8685-92 pubmed
    b>C4a anaphylatoxin is derived from the fourth component (C4) of the blood complement system...
  73. Marc M, Korosec P, Kosnik M, Kern I, Flezar M, Suskovic S, et al. Complement factors c3a, c4a, and c5a in chronic obstructive pulmonary disease and asthma. Am J Respir Cell Mol Biol. 2004;31:216-9 pubmed
    ..We sought to determine whether the levels of complement factors C3a, C4a, and C5a are elevated at the site of inflammation in patients with COPD and patients with asthma...
  74. 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...
  75. Palikhe A, Sinisalo J, Seppanen M, Valtonen V, Nieminen M, Lokki M. Human MHC region harbors both susceptibility and protective haplotypes for coronary artery disease. Tissue Antigens. 2007;69:47-55 pubmed
    ..46; 95% CI 0.24-0.88; P = 0.02) or together with the haplotype LTA+253a-LTA+633g-C4A3-C4B1 (OR 0.36; 95% CI 0.22-0.57; P = 0.00001)...
  76. Bennett S, Grant M, Creese A, Mangialasche F, Cecchetti R, Cooper H, et al. Plasma levels of complement 4a protein are increased in Alzheimer's disease. Alzheimer Dis Assoc Disord. 2012;26:329-34 pubmed publisher
    ..These data suggest that inflammatory processes, which have been shown to be involved in AD pathology in the brain, are also present in plasma. ..
  77. Bhattacharyya S, Feferman L, Tobacman J. Chondroitin sulfatases differentially regulate Wnt signaling in prostate stem cells through effects on SHP2, phospho-ERK1/2, and Dickkopf Wnt signaling pathway inhibitor (DKK3). Oncotarget. 2017;8:100242-100260 pubmed publisher
    ..GALNS) remove either the 4-sulfate group at the non-reducing end of chondroitin 4-sulfate (C4S) and dermatan sulfate, or the 6-sulfate group of chondroitin 6-sulfate, chondroitin 4,6-disulfate (chondroitin ..
  78. Reilly B, Skanes V, Levine R. Evidence showing that the 1105 and 1106 isotypic residues of the fourth component of human complement, C4A, are not involved in amide bond formation. Mol Immunol. 1994;31:761-9 pubmed
    Human C4A and C4B have different functions that may stem from their ability to bind hydroxyl or free amino groups on complement activating surfaces...
  79. Zafar G, Grimm E, Wei W, Johnson M, Ellerhorst J. Genetic deficiency of complement isoforms C4A or C4B predicts improved survival of metastatic renal cell carcinoma. J Urol. 2009;181:1028-34; discussion 1034 pubmed publisher
    ..gene is complement C4, which replicates as part of the RCCX module, can be present in multiple copies and exists as C4A and C4B isoforms. Deficiencies of either isoform are associated with autoimmunity...
  80. Behnsen J, Lessing F, Schindler S, Wartenberg D, Jacobsen I, Thoen M, et al. Secreted Aspergillus fumigatus protease Alp1 degrades human complement proteins C3, C4, and C5. Infect Immun. 2010;78:3585-94 pubmed publisher
    ..In summary, we identified a novel mechanism in A. fumigatus that contributes to evasion from the host complement attack. ..
  81. Yang X, Sun J, Gao Y, Tan A, Zhang H, Hu Y, et al. Genome-wide association study for serum complement C3 and C4 levels in healthy Chinese subjects. PLoS Genet. 2012;8:e1002916 pubmed publisher
    ..Our study is the first GWAS report which shows genetic components influence the levels of complement C3 and C4. Our significant findings provide novel insights of their related autoimmune, infectious diseases, and molecular mechanisms...
  82. Gao C, Catucci G, Castrignanò S, Gilardi G, Sadeghi S. Inactivation mechanism of N61S mutant of human FMO3 towards trimethylamine. Sci Rep. 2017;7:14668 pubmed publisher
    ..Thermodynamic and spectroscopic experiments reveal that the poor NADP+ binding affinity accelerates the C4a-hydroperoxyFAD intermediate decay, responsible for an unfavourable oxygen transfer to the substrate...
  83. Gibb A, Freeman A, Smith R, Edmonds S, Sim E. The interaction of soluble human complement receptor type 1 (sCR1, BRL55730) with human complement component C4. Biochim Biophys Acta. 1993;1180:313-20 pubmed
    ..An assay has been established using microtitre plates to explore the binding of sCR1 to the two isotypes of C4, C4A and C4B, and to C4 fragments. Specific binding of 125I-sCR1 to C4b and ammonia-treated C4 has been demonstrated...
  84. 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...
  85. Speiser P, White P. Structure of the human RD gene: a highly conserved gene in the class III region of the major histocompatibility complex. DNA. 1989;8:745-51 pubmed
    ..or D6S45) situated in the class III region of the human major histocompatibility complex (HLA) between the Bf and C4A complement genes. The coding region of the gene is contained in 10 exons spread over approximately 6 kb of DNA...
  86. Cohen D, Colvin R, Daha M, Drachenberg C, Haas M, Nickeleit V, et al. Pros and cons for C4d as a biomarker. Kidney Int. 2012;81:628-39 pubmed publisher
    ..This review provides an overview of the past, present, and future perspectives of C4d as a biomarker, focusing on its use in solid organ transplantation and discussing its possible new roles in autoimmunity and pregnancy. ..
  87. Feferman L, Deaton R, Bhattacharyya S, Xie H, Gann P, Melamed J, et al. Arylsulfatase B is reduced in prostate cancer recurrences. Cancer Biomark. 2017;: pubmed publisher
    Arylsulfatase B (ARSB) removes the 4-sulfate group from chondroitin 4-sulfate (C4S) and dermatan sulfate and is required for their degradation...
  88. Pfister C, Bourque S, Chatagnier O, Chiltz A, Fromentin J, Van Tuinen D, et al. Differential Signaling and Sugar Exchanges in Response to Avirulent Pathogen- and Symbiont-Derived Molecules in Tobacco Cells. Front Microbiol. 2017;8:2228 pubmed publisher
    ..mimicking pathogenic or mutualistic PMIs, namely cryptogein, a defense elicitor, and chitotetrasaccharide (CO4), which is secreted by mycorrhizal fungi...
  89. Lienenklaus S, Ames R, Tornetta M, Sarau H, Foley J, Crass T, et al. Human anaphylatoxin C4a is a potent agonist of the guinea pig but not the human C3a receptor. J Immunol. 1998;161:2089-93 pubmed
    The interaction of human anaphylatoxin C4a with the guinea pig (gp) and human (hu) C3a receptors (C3aR) was analyzed using human rC4a, which exhibited C4a-specific activity on guinea pig platelets...
  90. Fearon D. Activation of the alternative complement pathway. CRC Crit Rev Immunol. 1979;1:1-32 pubmed
  91. Chakravarti D, Campbell R, Porter R. The chemical structure of the C4d fragment of the human complement component C4. Mol Immunol. 1987;24:1187-97 pubmed
    ..residue suggests a structural basis for the origin of the different chemical reactivities of the C4 isotypes (C4A and C4B) and their serological difference in the expression of Rodgers or Chido blood group antigens...
  92. Gullstrand B, Martensson U, Sturfelt G, Bengtsson A, Truedsson L. Complement classical pathway components are all important in clearance of apoptotic and secondary necrotic cells. Clin Exp Immunol. 2009;156:303-11 pubmed publisher
    ..C1q was not more important than other classical pathway components, suggesting a role in additional pathogenetic processes in SLE other than clearance of apoptotic cells. ..