HGNC Approved Gene Symbol: C4BPB
Cytogenetic location: 1q32.1 Genomic coordinates (GRCh38): 1:207,088,860-207,099,993 (from NCBI)
The complement component C4b-binding protein is composed of 7 identical 70-kD alpha chains (120830), each containing a binding site for the complement protein C4b. Hillarp and Dahlback (1988) showed the presence in C4BP of a single copy of a unique 45-kD subunit. Called the beta chain, it binds protein S (176880). The subunit composition of C4BP in plasma is heterogeneous; a subform lacks the beta chain and does not bind protein S. The alpha chain is composed of 549 amino acid residues, and the 491 terminal residues can be divided into 8 short consensus repeats (SCRs).
Hillarp and Dahlback (1990) isolated and characterized full-length cDNA clones encoding the beta chain of human C4BP. The deduced amino acid sequence contained 3 SCRs homologous to those found in the alpha chain and a 60-amino acid nonrepeat region that is similar to the corresponding portion of the alpha chain.
Pardo-Manuel et al. (1990) showed by pulsed field gel electrophoresis that the alpha and beta chains of C4BP are closely situated in the same 420-kb SalI restriction fragment in a head-to-tail orientation. Presumably, they share regulatory sequences for coordinate regulation. Thus, there are 7 genes in the regulator of complement activation (RCA) gene cluster: C4BPA, C4BPB, MCP, CR1, CR2, DAF, and CFH. Hillarp et al. (1993) provided further information on the structure of the C4BPB gene.
Andersson et al. (1990) used cDNA probes for both the alpha- and beta-chains of human C4b-binding protein to localize their genes with an in situ hybridization technique to 1q32. The probes were also used to screen mouse-rat somatic cell hybrids using Southern blotting to localize the genes in the rat. Both genes were shown to be on chromosome 13 in the rat. These 2 genes and the gene for coagulation factor V represent a conserved chromosomal region in rat and man.
Rodriguez de Cordoba et al. (1994) used a human C4BPB cDNA probe to isolate and characterize a genomic DNA fragment that included the murine C4BPB gene. They found that it is present in single copy and maps close to the murine homolog of C4BPA on chromosome 1. However, in several inbred strains of Mus musculus and in Mus spretus, they demonstrated 2 inphase stop codons that are incompatible with the expression of a functional C4BPB polypeptide. It appeared that the loss of a functional C4BPB gene was a relatively recent event in the evolution of the mouse. Since the genetic change had become fixed, the mice lacking the C4BPB polypeptide may have enjoyed some kind of selective advantage.
Andersson, A., Dahlback, B., Hanson, C., Hillarp, A., Levan, G., Szpirer, J., Szpirer, C. Genes for C4b-binding protein alpha- and beta-chains (C4BPA and C4BPB) are located on chromosome 1, band 1q32, in humans and on chromosome 13 in rats. Somat. Cell Molec. Genet. 16: 493-500, 1990. [PubMed: 2237642] [Full Text: https://doi.org/10.1007/BF01233199]
Hillarp, A., Dahlback, B. Novel subunit in C4b-binding protein required for protein S binding. J. Biol. Chem. 263: 12759-12764, 1988. [PubMed: 2970465]
Hillarp, A., Dahlback, B. Cloning of cDNA coding for the beta-chain of human complement component C4b-binding protein: sequence homology with the alpha chain. Proc. Nat. Acad. Sci. 87: 1183-1187, 1990. [PubMed: 2300577] [Full Text: https://doi.org/10.1073/pnas.87.3.1183]
Hillarp, A., Pardo-Manuel, F., Ramos Ruiz, R., Rodriguez de Cordoba, R., Dahlback, B. The human C4b-binding protein beta-chain gene. J. Biol. Chem. 268: 15017-15023, 1993. [PubMed: 8325877]
Pardo-Manuel, F., Rey-Campos, J., Hillarp, A., Dahlback, B., Rodriguez de Cordoba, S. Human genes for the alpha and beta chains of complement C4b-binding protein are closely linked in a head-to-tail arrangement. Proc. Nat. Acad. Sci. 87: 4529-4532, 1990. [PubMed: 2352933] [Full Text: https://doi.org/10.1073/pnas.87.12.4529]
Rodriguez de Cordoba, S., Perez-Blas, M., Ramos-Ruiz, R., Sanchez-Corral, P., Pardo-Manuel de Villena, F., Rey-Campos, J. The gene coding for the beta-chain of C4b-binding protein (C4BPB) has become a pseudogene in the mouse. Genomics 21: 501-509, 1994. [PubMed: 7959726] [Full Text: https://doi.org/10.1006/geno.1994.1308]