Dancing with Complement C4 and the RP-C4-CYP21-TNX (RCCX) Modules of the Major Histocompatibility Complex

C. Yung Yu, Erwin K. Chung, Yan Yang, Carol A. Blanchong, Natalie Jacobsen, Kapil Saxena, Zhenyu Yang, Webb Miller, L. Varga, G. Füst

Research output: Contribution to journalArticle

42 Citations (Scopus)

Abstract

The number of the complement component C4 genes varies from 2 to 8 in a diploid genome among different human individuals. Three quarters of the C4 genes in Caucasian populations have the endogenous retrovirus, HERV-K(C4), in the ninth intron. The remainder does not. The C4 serum proteins are highly polymorphic and their concentrations vary from 100 to ∼1000 μg/ml. There are two distinct classes of C4 protein, C4A and C4B, which have diversified to fulfill (a) the opsonization/immunoclearance purposes and (b) the well-known complement function in the killing of microbes by lysis and neutralization, respectively. Many infectious and autoimmune diseases are associated with complete or partial deficiency of C4A and/or C4B. The adverse effects of high C4 gene dosages, however, are just emerging, as the concepts of human C4 genetics are revised and accurate techniques are applied to distinguish partial deficiencies from differential expression caused by unequal C4A and C4B gene dosages and gene sizes. This review attempts to dissect the sophisticated genetics of complement C4A and C4B. The emphases are on the qualitative and quantitative diversities of C4 genotypes and phenotypes. The many allotypic variants and the processed products of human and mouse C4 proteins are described. The modular variation of C4 genes together with the serine/threonine nuclear kinase gene RP, the steroid 21-hydroxylase CYP21, and extracellular matrix protein TNX (RCCX modules) are investigated for the effects on homogenization of C4 protein polymorphisms, and on the unequal genetic crossovers that knocked out the functions of CYP21 and/or TNX. Furthermore, the influence of the endogenous retrovirus HERV-K(C4) on C4 gene expression and the dispersal of HERV-K(C4) family members in the human genome are discussed.

Original languageEnglish
Pages (from-to)217-292
Number of pages76
JournalProgress in Nucleic Acid Research and Molecular Biology
Volume75
DOIs
Publication statusPublished - 2003

Fingerprint

Dancing
Complement C4
Endogenous Retroviruses
Major Histocompatibility Complex
Gene Dosage
Genes
Steroid 21-Hydroxylase
Extracellular Matrix Proteins
Protein-Serine-Threonine Kinases
Medical Genetics
Human Genome
Diploidy
Introns
Autoimmune Diseases
Communicable Diseases
Blood Proteins
Proteins
Genotype
Genome
Phenotype

Keywords

  • Complement C4
  • Diversity
  • Endogenous retrovirus
  • Evolution
  • Gene dosage
  • Gene size
  • Partial gene duplication
  • Polygenic variation
  • Polymorphism
  • Recombination
  • Steroid 21-hydroxylase
  • Tenascin-X

ASJC Scopus subject areas

  • Molecular Biology

Cite this

Dancing with Complement C4 and the RP-C4-CYP21-TNX (RCCX) Modules of the Major Histocompatibility Complex. / Yung Yu, C.; Chung, Erwin K.; Yang, Yan; Blanchong, Carol A.; Jacobsen, Natalie; Saxena, Kapil; Yang, Zhenyu; Miller, Webb; Varga, L.; Füst, G.

In: Progress in Nucleic Acid Research and Molecular Biology, Vol. 75, 2003, p. 217-292.

Research output: Contribution to journalArticle

Yung Yu, C. ; Chung, Erwin K. ; Yang, Yan ; Blanchong, Carol A. ; Jacobsen, Natalie ; Saxena, Kapil ; Yang, Zhenyu ; Miller, Webb ; Varga, L. ; Füst, G. / Dancing with Complement C4 and the RP-C4-CYP21-TNX (RCCX) Modules of the Major Histocompatibility Complex. In: Progress in Nucleic Acid Research and Molecular Biology. 2003 ; Vol. 75. pp. 217-292.
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