Reactome | Conversion of C4 into C4a and C4b

Conversion of C4 into C4a and C4b

Stable Identifier

R-HSA-166753

Type

Reaction [transition]

Species

Homo sapiens

Compartment

extracellular region, plasma membrane

Locations in the PathwayBrowser

Expand all

General

SBML | | PDF

SVG | | PPTX | SBGN

Click the image above or here to open this reaction in the Pathway Browser
The layout of this reaction may differ from that in the pathway view due to the constraints in pathway layout

The alpha chain of C4 is cleaved, releasing an N-terminal portion of this chain as C4a. The beta and gamma chains are not cleaved and remain linked to the alpha chain by disulfide bonds (Nagasawa et al. 1976, 1980). The resulting C4b heterotrimer undergoes a gross conformational change; the internal thioester in C4b becomes exposed and able to form covalent bonds with surrounding molecules (Law and Dodds 1997). A large proportion of the bonds formed are with water, but some will attach C4b to biological surfaces (Rother et al. 1998). This irreversible reaction can be catalyzed by activated MBL, generated through the lectin pathway of complement activation (Fujita et al. 2004; Hajela et al. 2002), and by activated C1, generated through the classical pathway (Muller-Eberhard and Lepow 1965).

N.B. Humans have two highly polymorphic loci for Complement factor 4, C4A and C4B. C4A alleles carry the Rodgers (Rg) blood group antigens while the C4B alleles carry the Chido (Ch) blood group antigens. The two loci encode non identical C4 peptides; C4 derived from C4A reacts more rapidly with the amino groups of peptide antigens while C4B allotypes react more rapidly with the hydroxyl group of carbohydrate antigens. The names of the two loci are always represented in uppercase. C4a and C4b refer to the peptide products of Complement Factor 4 cleavage.

Literature References

PubMed ID	Title	Journal	Year
12396008	The biological functions of MBL-associated serine proteases (MASPs) Hajela, K, Kojima, M, Ambrus, G, Wong, KH, Moffatt, BE, Ferluga, J, Hajela, S, Gal, P, Sim, RB	Immunobiology	2002
15199963	The lectin-complement pathway--its role in innate immunity and evolution Fujita, T, Matsushita, M, Endo, Y	Immunol Rev	2004
14280442	C'1 esterase effect on activity and physicochemical properties of the fourth component of complement Muller-Eberhard, HJ, Lepow, IH	J Exp Med	1965