C4b-binding protein beta chain (C4BPB)
The protein contains 252 amino acids for an estimated molecular weight of 28357 Da.
Controls the classical pathway of complement activation. It binds as a cofactor to C3b/C4b inactivator (C3bINA), which then hydrolyzes the complement fragment C4b. It also accelerates the degradation of the C4bC2a complex (C3 convertase) by dissociating the complement fragment C2a. It also interacts with anticoagulant protein S and with serum amyloid P component. The beta chain binds protein S. (updated: Oct. 10, 2018)
Protein identification was indicated in the following studies:
Methods
The following articles were analysed to gather the proteome content of erythrocytes.
The gene or protein list provided in the studies were processed using the ID mapping API of Uniprot in September 2018. The number of proteins identified and mapped without ambiguity in these studies is indicated below.
Only Swiss-Prot entries (reviewed) were considered for protein evidence assignation.
| Publication | Identification 1 | Uniprot mapping 2 | Not mapped / Obsolete | TrEMBL | Swiss-Prot |
|---|---|---|---|---|---|
| Goodman (2013) | 2289 (gene list) | 2278 | 53 | 20599 | 2269 |
| Lange (2014) | 1234 | 1234 | 7 | 28 | 1224 |
| Hegedus (2015) | 2638 | 2622 | 0 | 235 | 2387 |
| Wilson (2016) | 1658 | 1528 | 170 | 291 | 1068 |
| d'Alessandro (2017) | 1826 | 1817 | 2 | 0 | 1815 |
| Bryk (2017) | 2090 | 2060 | 10 | 108 | 1942 |
| Chu (2018) | 1853 | 1804 | 55 | 362 | 1387 |
1 as available in the article and/or in supplementary material
2 uniprot mapping returns all protein isoforms as one entry
The compilation of older studies can be retrieved from the Red Blood Cell Collection database.
The data and differentiation stages presented below come from the proteomic study and analysis performed by our partners of the GReX consortium, more details are available in their published work.
This protein is annotated as membranous in Gene Ontology.
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| Variant | Description |
|---|---|
| dbSNP:rs56258224 | |
| dbSNP:rs1803226 |
Biological Process
Blood coagulation
Complement activation, classical pathway
Innate immune response
Negative regulation of complement activation, classical pathway
Positive regulation of protein catabolic process
Regulation of complement activation
Regulation of opsonization
Response to symbiotic bacterium
Cellular Component
Extracellular region
Extracellular space
Obsolete other organism cell
Plasma membrane
Molecular Function
The reference OMIM entry for this protein is 120831
Complement component 4-binding protein, beta chain; c4bpb
CLONING
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.GENE STRUCTURE
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.MAPPING
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.EVOLUTION
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. ... More on the omim web site
Oct. 19, 2018: Additional information
Initial protein addition to the database. This entry was referenced in Bryk and co-workers. (2017).
Oct. 19, 2018: Protein entry updated
Automatic update: OMIM entry 120831 was added.