C4A Gene

The C4A gene (Complement C4A/Rodgers blood group) is a protein-coding gene located on 6p21.33. The C4A gene is located in the major histocompatibility complex (MHC) class III region on chromosome 6. There are different haplotypes of this gene cluster, so individuals may have 1, 2, or 3 copies of this gene. Two transcript variants encoding different isoforms have been found for the C4A gene.

The C4A gene encodes the alpha chain of complement factor 4, which is part of the classical activation pathway. The protein is expressed as a single-chain precursor that is proteolytically cleaved into a trimer of alpha, beta, and gamma chains prior to secretion. The alpha chain is cleaved to release C4 anaphylatoxin, an antimicrobial peptide and a mediator of local inflammation. Deficiency of the C4a protein is associated with systemic lupus erythematosus and type I diabetes mellitus .

Diseases associated with C4A include complement component 4A deficiency . Associated pathways include immune response, lectin-induced complement pathway, and innate immune system responses.

The C4a protein encoded by this gene is a non-enzymatic component of C3 and C5 convertases and thus essential for the propagation of the classical complement pathway. Binds covalently to immunoglobulins and immune complexes. The C4A isotype is responsible for effective binding to form amide bonds with immune aggregates or protein antigens, while the C4B isotype catalyzes transacylation of the thioester carbonyl group to form ester bonds with carbohydrate antigens.

Anaphylatoxin C4a, derived from proteolytic degradation of complement C4, is a mediator of local inflammatory processes. It induces smooth muscle contraction, increases vascular permeability, and causes the release of histamine from mast cells and basophilic leukocytes.

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