|Protein Name||Complement C4|
|Amino Acid Lenth||920|
|Protein Existence Status||Reviewed: Experimental evidence at protein level|
|Protein Function||most heterogeneous protein of the complement system; act as opsonizing molecules; C4b2a complex (the CP C3 convertase) remains on the activator and mediates downstream activation by cleaving C3 into C3b and C3a; C4b may offer a nucleophile for the cleavage of the thioester in nascent C3b|
|Biochemical Properties||C4A is more prone to attach to amine groups of an activator, whereas C4B reacts preferentially with hydroxyl groups;|
|Significance in milk||recruit inflammatory leucocytes to the sites of an inflammation and activate their effector mechanisms|
|PTMs||Glycosylated: 4 N linked glycosylation site; α and ß-chains are glycosylated, but no accurate assessment of carbohydrate content in the γ-chain has been reported; C4 in human plasma contains mannose, galactose, glucosamine and sialic acid; contain complex biantennary glycans with varying degrees of sialylation; Human C4A recovered from cerebrospinal fluid was identified to contain an O-linked core 1 glycan; sulfation of three tyrosine residues|
|Additional Comments||Carbohydrate incorporation can be blocked by tunicamycin; underglycosylated pro-C4 protein is more rapidly catabolized than the corresponding fully glycosylated protein; underglycosylated native C4, produced in the presence of tunicamycin, had approximately the same specific biological activity as glycosylated C4|
|Bibliography||1. Akita EM, Li-Chan ECY. Isolation of Bovine Immunoglobulin G Subclasses from Milk, Colostrum, and Whey Using Immobilized Egg Yolk Antibodies. J Dairy Sci. 1998;81(1):54–63. |
2. Matthews WJ, Goldberger G, Marino JT, Einstein LP, Gash DJ, Colten HR. Complement proteins C2, C4 and factor B. Effect of glycosylation on their secretion and catabolism. Biochem J. 1982;204(3):839–46.
3. Zimmerman B, Kelly B, McMillan BJ, Seegar TCM, Dror RO, Kruse AC, et al. Crystal Structure of a Full-Length Human Tetraspanin Reveals a Cholesterol-Binding Pocket. Cell. 2016 Nov 3;167(4):1041-1051.e11.