C4b-binding protein alpha chain (C4BPA)
The protein contains 597 amino acids for an estimated molecular weight of 67033 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. Alpha chain binds C4b. It interacts also with anticoagulant protein S and with serum amyloid P component. (updated: March 4, 2015)
Protein identification was indicated in the following studies:
- Goodman and co-workers. (2013) The proteomics and interactomics of human erythrocytes. Exp Biol Med (Maywood) 238(5), 509-518.
- Hegedűs and co-workers. (2015) Inconsistencies in the red blood cell membrane proteome analysis: generation of a database for research and diagnostic applications. Database (Oxford) 1-8.
- D'Alessandro and co-workers. (2017) Red blood cell proteomics update: is there more to discover? Blood Transfus. 15(2), 182-187.
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:rs55867570 | |
| dbSNP:rs17020956 | |
| dbSNP:rs45574833 | |
| dbSNP:rs4844573 | |
| empty | |
| dbSNP:rs1801341 |
Biological Process
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
The reference OMIM entry for this protein is 120830
Complement component 4-binding protein, alpha; c4bpa
C4b receptor; c4bp complement component 4-binding protein, alpha-like 1, included; c4bpal1, included
DESCRIPTION
C4b (120820)-binding protein is involved in regulation of the complement system. It is a multimeric protein comprising 7 identical alpha chains, encoded by C4BPA, and a single beta chain, encoded by C4BPB (120831). The alpha and beta chains have molecular masses of 70 and 45 kD, respectively. Both subunits belong to a superfamily of proteins composed predominantly of tandemly arranged short consensus repeats (SCR) of approximately 60 amino acids in length (Aso et al., 1991).CLONING
By isoelectric focusing under completely denaturing conditions, Rodriguez de Cordoba et al. (1983, 1984) identified 2 allelic variants of C4BP. Matsuguchi et al. (1989) showed that proline-rich protein (PRP), a glycoprotein present in chylomicrons, is identical to C4BP.GENE FUNCTION
C4BP of man has been studied by Gigli et al. (1979) and Nagasawa and Stroud (1980). Gigli et al. (1979) showed that C4BP is an essential cofactor for C3b inactivator (CFI; 217030) in the proteolytic cleavage of C4b and, to a lesser extent, of C3b (120700), and functions as the regulator of C3 convertase of the classical pathway. Kaidoh et al. (1981) stated that the C3 convertase of the classical pathway consists of C2 (613927) and C4; that of the alternative pathway of factor B (CFB; 138470) and C3 (120700). Each C3 convertase plays a key role in the amplification process of complement activation. Brodeur et al. (2003) identified a 23-kD protein that bound CD40 (109535) as C4BP-alpha. Flow cytometric analysis demonstrated binding of C4BP to human B-cell lines expressing CD40, but not to cells from CD40-deficient patients. Competitive binding analysis showed that CD40LG (300386) and C4BP bound distinct sites on CD40. C4BP induced proliferation, upregulation of CD54 (ICAM1; 147840) and CD86 (601020) surface expression, and, together with IL4 (147780), IgE synthesis in normal B cells, but not in B cells from patients with CD40 or IKBKG (300248) deficiencies. Immunohistochemical analysis showed that C4BP colocalized with CD40 on B cells in tonsillar germinal centers. Brodeur et al. (2003) proposed that C4BP is an activating ligand for CD40 and represents an interface between complement and B-cell activation. Strains of Neisseria gonorrhoeae use their outer membrane porin (Por) molecules to bind C4BP and resist killing by human, but not rodent, rabbit, and nonhuman primate, serum complement. The lack of susceptibility to N. gonorrhoeae infection in nonhuman species prevents the development of an animal model to study the infection in vivo. Ngampasutadol et al. (2005) found that gonococci expressing Por1B, but not Por1A, were resistant to killing by chimpanzee serum. Addition of human C4BP to animal sera rescued N. gonorrhoeae from killing. Nonhuman C4bp did not bind N. gonorrhoeae. Comparative sequence analysis suggested 4 potential residues in human C4BP that may be critical for its interaction with Por1A. Ngampasutadol et al. (2005) concluded that C4BP sequence differences account for the restriction of serum resistance of N. gonorrhoeae to humans and, in some instances, chimpanzees.GENE STRUCTURE
Aso et al. (1991) found that the C4BPA gene comprises 12 exons and spans about 40 kb. Each of the 8 SCRs that constitute the N-terminal 491 residues is encoded by a single exon, except for the second, which is encoded by 2 separate exons.MAPPING
Rodriguez de Cordoba et al. (1984) studied 3 pedigrees informative for segre ... More on the omim web site
Feb. 2, 2018: Protein entry updated
Automatic update: Uniprot description updated
Dec. 19, 2017: Protein entry updated
Automatic update: Uniprot description updated
Nov. 23, 2017: Protein entry updated
Automatic update: Uniprot description updated
March 16, 2016: Protein entry updated
Automatic update: OMIM entry 120830 was added.
Jan. 24, 2016: Protein entry updated
Automatic update: model status changed