Complement component 4B explained

Complement component 4B (Chido blood group) is a kind of the Complement component 4 protein that in humans is encoded by the C4B gene.^[1]

This gene encodes the basic form of complement factor 4, part of the classical activation pathway. The protein is expressed as a single chain precursor which is proteolytically cleaved into a trimer of alpha, beta, and gamma chains prior to secretion. The trimer provides a surface for interaction between the antigen-antibody complex and other complement components. The alpha chain may be cleaved to release C4 anaphylatoxin, a mediator of local inflammation. Deficiency of this protein is associated with systemic lupus erythematosus. This gene localizes to the RCCX locus within the major histocompatibility complex (MHC) class III region on chromosome 6.^{[2] [3]} Varying haplotypes of this gene cluster exist, such that individuals may have 1, 2, or 3 copies of this gene. In addition, this gene exists as a long form and a short form due to the presence or absence of a 6.4 kb endogenous HERV-K retrovirus in intron 9. [provided by RefSeq, Jul 2008].^[4] Each copy of the gene, due to five adjacent nucleotide substitutions cause four amino acid changes and immunological subfunctionalization,^[5] can be of one of two types: C4A and C4B.^[6] Each gene contains 41 exons and has a dichotomous size variation between approximately 22 kb and 16 kb, with the longer variant being the result of the integration of the endogenous retrovirus HERV-K(C4) into intron 9.^[3]

See also

• Complement component 4
  • Complement component 4A
• HLA A1-B8-DR3-DQ2 haplotype
• Complement system
• Complement deficiency

Further reading

• Yu CY . Molecular genetics of the human MHC complement gene cluster . Experimental and Clinical Immunogenetics . 15 . 4 . 213–30 . 1998 . 10072631 . 10.1159/000019075 . 25061446 .
• Yang Z, Mendoza AR, Welch TR, Zipf WB, Yu CY . 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 associations . The Journal of Biological Chemistry . 274 . 17 . 12147–56 . Apr 1999 . 10207042 . 10.1074/jbc.274.17.12147 . free .
• Blom AM, Webb J, Villoutreix BO, Dahlbäck B . 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 . 274 . 27 . 19237–45 . Jul 1999 . 10383431 . 10.1074/jbc.274.27.19237 . free .
• Tas SW, Klickstein LB, Barbashov SF, Nicholson-Weller A . C1q and C4b bind simultaneously to CR1 and additively support erythrocyte adhesion . Journal of Immunology . 163 . 9 . 5056–63 . Nov 1999 . 10.4049/jimmunol.163.9.5056 . 10528211 . 46016135 . free .
• Aoki H, Takizawa F, Tsuji S, Nagasawa S . Elongation factor-1alpha as a homologous complement activator of Jurkat cells . International Journal of Molecular Medicine . 6 . 1 . 87–92 . Jul 2000 . 10851272 . 10.3892/ijmm.6.1.87 .
• Teisberg P, Akesson I, Olaisen B, Gedde-Dahl T, Thorsby E . Genetic polymorphism of C4 in man and localisation of a structural C4 locus to the HLA gene complex of chromosome 6 . Nature . 264 . 5583 . 253–4 . Nov 1976 . 1088823 . 10.1038/264253a0 . 1976Natur.264..253T . 4241132 .
• Pan Q, Ebanks RO, Isenman DE . Two clusters of acidic amino acids near the NH2 terminus of complement component C4 alpha'-chain are important for C2 binding . Journal of Immunology . 165 . 5 . 2518–27 . Sep 2000 . 10946278 . 10.4049/jimmunol.165.5.2518 . free .
• Kramer J, Harcos P, Prohászka Z, Horváth L, Karádi I, Singh M, Császár A, Romics L, Füst G . Frequencies of certain complement protein alleles and serum levels of anti-heat-shock protein antibodies in cerebrovascular diseases . Stroke: A Journal of Cerebral Circulation . 31 . 11 . 2648–52 . Nov 2000 . 11062289 . 10.1161/01.STR.31.11.2648 . 14128121 .
• Dragon-Durey MA, Rougier N, Clauvel JP, Caillat-Zucman S, Remy P, Guillevin L, Liote F, Blouin J, Ariey F, Lambert BU, Kazatchkine MD, Weiss L . Lack of evidence of a specific role for C4A gene deficiency in determining disease susceptibility among C4-deficient patients with systemic lupus erythematosus (SLE) . Clinical and Experimental Immunology . 123 . 1 . 133–9 . Jan 2001 . 11168010 . 1905972 . 10.1046/j.1365-2249.2001.01438.x .
• Laich A, Sim RB . Complement C4bC2 complex formation: an investigation by surface plasmon resonance . Biochimica et Biophysica Acta (BBA) - Protein Structure and Molecular Enzymology . 1544 . 1–2 . 96–112 . Jan 2001 . 11341920 . 10.1016/S0167-4838(00)00208-9 .

Notes and References

1. Web site: Entrez Gene: Complement component 4B (Chido blood group). 2012-01-27 .
2. Zhou D, Rudnicki M, Chua GT, Lawrance SK, Zhou B, Drew JL, Barbar-Smiley F, Armstrong TK, Hilt ME, Birmingham DJ, Passler W, Auletta JJ, Bowden SA, Hoffman RP, Wu YL, Jarjour WN, Mok CC, Ardoin SP, Lau YL, Yu CY . Human Complement C4B Allotypes and Deficiencies in Selected Cases With Autoimmune Diseases . Front Immunol . 12 . 739430 . 2021 . 34764957 . 8577214 . 10.3389/fimmu.2021.739430 . free .
3. Carrozza C, Foca L, De Paolis E, Concolino P . Genes and Pseudogenes: Complexity of the RCCX Locus and Disease . Front Endocrinol (Lausanne) . 12 . 709758 . 2021 . 34394006 . 8362596 . 10.3389/fendo.2021.709758 . free .
4. Web site: Entrez Gene: Complement component 4B (Chido blood group). 2012-01-27 .
5. Bánlaki Z, Szabó JA, Szilágyi Á, Patócs A, Prohászka Z, Füst G, Doleschall M . Intraspecific evolution of human RCCX copy number variation traced by haplotypes of the CYP21A2 gene . Genome Biol Evol . 5 . 1 . 98–112 . 2013 . 23241443 . 3595039 . 10.1093/gbe/evs121 .
6. Doleschall M, Luczay A, Koncz K, Hadzsiev K, Erhardt É, Szilágyi Á, Doleschall Z, Németh K, Török D, Prohászka Z, Gereben B, Fekete G, Gláz E, Igaz P, Korbonits M, Tóth M, Rácz K, Patócs A . A unique haplotype of RCCX copy number variation: from the clinics of congenital adrenal hyperplasia to evolutionary genetics . Eur J Hum Genet . 25 . 6 . 702–710 . June 2017 . 28401898 . 5477366 . 10.1038/ejhg.2017.38 .