| Post Translational Modifications | Prior to secretion, the single-chain precursor is enzymatically cleaved by plasminogen (PLG) to yield non-identical chains alpha, beta and gamma. During activation of the complement systems, the alpha chain is cleaved into C4a and C4b by different proteases depending on the complement pathway: C4b stays linked to the beta and gamma chains, while C4a is released in the plasma. The alpha chain is cleaved by C1S to generate C4a and C4b following activation by the classical complement system. The alpha chain is cleaved to generate C4a and C4b by MASP2 following activation by the lectin complement system. The alpha chain is cleaved by GZMK to generate C4a and C4b following activation by the GZMK complement system. Further degradation of C4b by C1 into the inactive fragments C4c and C4d blocks the generation of C3 convertase. The proteolytic cleavages often are incomplete so that many structural forms can be found in plasma. Complement C4b-A: Upon activation, the internal thioester bond reacts with carbohydrate antigens on the target surface to form amide or ester bonds, leading to covalent association with the surface of pathogens. Complement C4b-A: Ser-1236 of complement C4b interacts with complement C3b via a thioester linkage. N- and O-glycosylated. O-glycosylated with a core 1 or possibly core 8 glycan. |
| Function | Precursor of non-enzymatic components of the classical, lectin and GZMK complement pathways, which consist in a cascade of proteins that leads to phagocytosis and breakdown of pathogens and signaling that strengthens the adaptive immune system. Complement C4b-A: Non-enzymatic component of C3 and C5 convertases. Generated following cleavage by complement proteases (C1S, MASP2 or GZMK, depending on the complement pathway), it covalently attaches to the surface of pathogens, where it acts as an opsonin that marks the surface of antigens for removal. It then recruits the serine protease complement C2b to form the C3 and C5 convertases, which cleave and activate C3 and C5, respectively, the next components of the complement pathways. Complement C4b-A isotype is responsible for effective binding to form amide bonds with immune aggregates or protein antigens, while complement C4b-B isotype catalyzes the transacylation of the thioester carbonyl group to form ester bonds with carbohydrate antigens. C4a anaphylatoxin: Putative humoral mediator released following cleavage by complement proteases (C1S, MASP2 or GZMK, depending on the complement pathway). While it is strongly similar to anaphylatoxins, its role is unclear. Was reported to act as a mediator of local inflammatory process.however these effects were probably due to contamination with C3a and/C5a anaphylatoxins in biological assays. |
| Protein Name | Complement C4-AAcidic Complement C4C3 And Pzp-Like Alpha-2-Macroglobulin Domain-Containing Protein 2 Cleaved Into - Complement C4 Beta Chain - Complement C4-A Alpha Chain - C4a Anaphylatoxin - Complement C4b-AComplement C4b-Alpha' Chain - Complement C4d-A - Complement C4 Gamma Chain |
| Database Links | Reactome: R-HSA-166663Reactome: R-HSA-174577Reactome: R-HSA-381426Reactome: R-HSA-8957275Reactome: R-HSA-977606 |
| Cellular Localisation | SecretedSynapseCell ProjectionAxonDendriteC4a Anaphylatoxin: SecretedComplement C4b-A: SecretedCell SurfaceCovalently Associated With The Surface Of Pathogens: The Internal Thioester Bond Reacts With Carbohydrate Antigens On The Target Surface To Form Amide Or Ester Bonds |
| Alternative Antibody Names | Anti-Complement C4-A antibodyAnti-Acidic Complement C4 antibodyAnti-C3 And Pzp-Like Alpha-2-Macroglobulin Domain-Containing Protein 2 Cleaved Into - Complement C4 Beta Chain - Complement C4-A Alpha Chain - C4a Anaphylatoxin - Complement C4b-A antibodyAnti-Complement C4b-Alpha' Chain - Complement C4d-A - Complement C4 Gamma Chain antibodyAnti-C4A antibodyAnti-CO4 antibodyAnti-CPAMD2 antibody |
Information sourced from Uniprot.org
