Amino acid sequence of human plasma alpha 1B-glycoprotein: homology to the immunoglobulin supergene family.

Abstract

The complete amino acid sequence has been determined for a1B-glycoprotein (a1B), a protein of unknown function present in human plasma. This protein (Mr 63,000) consists of a single polypeptide chain N-linked to four glucosamine oligosaccharides. The polypeptide has five intrachain disulfide bonds and contains 474 amino acid residues. Analysis of the amino acid sequence by several computer programs shows that a1B exhibits internal duplication and consists of five repeating structural domains, each containing about 95 amino acids and one disulfide bond. a1B has a unique amino acid sequence. However, several domains of a1B, especially the third, show statistically significant homology to variable regions of certain immunoglobulin light and heavy chains. ajB also exhibits sequence similarity to other members of the immunoglobulin supergene family such as the receptor for transepithelial transport of IgA and IgM and the secretory component of human IgA. Because of its internal duplication and its sequence homology to immunoglobulin-like proteins, ajB appears to have evolved from an ancestral gene similar to that of the immunoglobulin supergene family.We present the complete amino acid sequence of human aB-glycoprotein (aB) and show that it is homologous in structure to certain domains in immunoglobulins and in the receptor for polymeric immunoglobulins (poly-IgR). a1B was described by Schultze et al. (1) as an "easily precipitable al-glycoprotein" present in human plasma and was later shown to be the same as the aB-glycoprotein observed by Burtin (2) on immunoelectrophoresis of serum. a1B has been reported to have a molecular weight of 68,000 and a carbohydrate content of 13.3% (3). The polypeptide structure was puzzling because a1B appeared to exist in serum in two molecular forms, one having a single polypeptide chain (Mr = 68,000), the other seeming to have two subunits (Mr 50,000 and 20,000). Like most plasma glycoproteins, aIB exhibits electrophoretic heterogeneity near its isoelectric point (pH 4.4-4.6). a1B is present in normal adult serum at an average concentration of 22 mg/dl; however, no change in disease has been observed nor has any biological function been proposed (3). No information on the amino acid sequence of a1B has been reported previously. Thus, aBglycoprotein is one of a series ofhuman plasma glycoproteins of unidentified physiological function that have been highly purified and have been characterized by physicochemical methods but whose primary structure was unknown (3, 4).We are engaged in a program of study of such proteins with the objectives of determining their primary structures, their relationships to other plasma proteins, and their possible functions. Earlier we reported the complete amino acid sequence of p2-glycoprotein I (5), ceruloplasmin (6), hemopexin (7), and leucine-rich a2-glycoprotein (8). A notable structural feature of these four proteins, which is shared by many other plasma proteins (9, 10), is a pattern of internal duplication in amino acid sequence that i...

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