The early studies vastly expanded the knowledge of the<unk>  complex, laying down the foundations that paved the way to discovering the gene and protein structures. C. Yu successfully determined the complete sequence of the human<unk><unk> A gene. In the findings, the whole genome was found to have of<unk> 1 exons, with a total of 1744 residues (despite avoiding the sequence of a large Intron 9). The<unk>  protein is synthesized into a single chain precursor, which then undergoes proteolytic cleavage into three chains (in order of how they are chained, β-α-γ). The β-chain consists of 656 residues, coded by exons 1-16. The most prominent aspect of the β-chain is the presence of a large intron, ranging from six to seven kilobases in size. It is present in the first locus (coding for<unk> A) for all<unk>  genes and in the second locus (coding for<unk> B) only in a few<unk>  genes. The α-chain consists of residues 661-1428, encoding exons 16-33. Within this chain, two cleavage sites marked by exons 23 and 30 produces the<unk> d fragment (where the thioester, Ch/Rg antigens, and isotypic residues are located); moreover, most of the polymorphic sites cluster in this region. The γ-chain consists of 291 residues, encoding exons 33-41. Unfortunately, no specific function has been attributed to the γ-chain. The study completed by Vaishnaw et al. sought to identify the key region and factors related to the efforts of gene expression of the<unk>  gene. Their research concluded with the fact that the Sp1 binding site (positioned at -59 to -49) plays an important role in accurately starting basal transcription of<unk> . Utilization of electromobility shift assays and DNase I footprint analyses demonstrated specific DNA-protein correlations of the<unk>  promoter at the nuclear factor 1, two E box (-98 to -93 and -78 to -73), and Sp1 binding domains. These findings were later added to in another extensive study, that found a third E box site. In addition, the same findings postulated that two physical entities within the gene sequence could have a role in the expression levels of human<unk> A and<unk> B, which include the both presence of the endogenous retrovirus that can have positive or negative regulatory influences affecting<unk>  transcription and the varying genetic environment (dependent on which genetic modular component is present) past position -1524. To provide more context, in the latter study, the previously noted bimodular structure <unk> A-C4B) has been updated to a quadrimodular structure of one to four discrete segments, containing one or more RP-C4-CYP21-TNX (RCCX) modules. The size of either<unk> A or<unk> B gene can be 21 kb (long, L) or 14.6 kb (short, S). Also, the long<unk>  gene uniquely contains a retrovirus HERV-K<unk>  in its intron 9 that imposes transcription of an extra 6.36 kb, hence the “longer” string of gene. Thus,<unk>  genes have a complex pattern of variation in gene size, copy number, and polymorphisms. Examples of these mono-, bi-, tri-, and quadri-modular structures include: L or S (monomodular with one long or short<unk>  gene), LL or LS or SS (bimodular with a combination of homozygous or heterozygous L or S genes), LLL or LLS or LSS (trimodular RCCX with three L or S<unk>  genes), LLLL (quadrimodular structure with four L or S<unk>  genes). Not all the structural groups have the same percentage of appearance, possibly even further differences within separate ethnic groups. For example, the Caucasian population studied showed 69% bimodular configuration <unk> A-C4B,<unk> A-C4A, or<unk> B-C4B) and 31% trimodular configuration (equally split between LLL as<unk> A-C4A-C4B or LSS as<unk> A-C4B-C4B). Regarding<unk>  protein sequence polymorphism, a total of 24 polymorphic residues were found. Among them, the β-chain expressed of five, as the α-chain and γ-chain produced 18 and one, respectively. These polymorphisms can be further categorized into groups: 1) four isotypic residues at specific positions, 2) Ch/Rg antigenic determinants at specific positions, 3) C5 binding sites,<unk>  private allelic residues. Additionally, the same study identified the expression of human<unk> <unk>  transcripts in multiple tissues. The results of a Northern blot analysis, using a<unk> d probe and RD probe as positive control, showed that the liver contains the majority of transcripts throughout the body. Even so, moderate quantities were expressed in adrenal cortices/medulla, thyroid, and kidney.
Complement component 4
Complement component 3
Complement component 5a
Complement receptor 1
Major basic protein
Neutrophil elastase
Macrophage-activating factor
Immunophilins