Back to your search result

Description

Protein AMBP (UniProt P02760, also known as alpha-1-microglobulin/bikunin precursor) is transcribed from the AMBP (also known as HCP, HI30, IATIL, ITIL, ITILC) gene (Gene ID 259) in human as a precursor protein with a signal peptide (a.a. 1-19), posttranslational cleavages produce Alpha-1-microglobulin (a.a. 20-203, A1M, Alpha-1 microglycoprotein, Complex-forming glycoprotein heterogeneous in charge, Protein HC), bikunin (a.a. 206-352, Inter-alpha-trypsin inhibitor light chain, ITI-LC, EDC1, HI-30, Uronic-acid-rich protein), and Trypstatin (a.a. 284-344). Bikunin is a proteoglycan (PG) that contains a single chondroitin sulfate (CS) glycosaminoglycan (GAG) chain with 27-39 monosaccharides attached to Ser10 of the mature core protein. Bikunin GAG has a non-sulfated domain consisting of 6-22 monosaccharides on the non-reducing end and a sulfated domain of 12-18 monosaccharides on the reducing end, with the sulfation occuring exclusively at the fourth carbon of the GalNAc residues. During the synthesis of bikunin by hepatocytes, C-terminal aspartate residues of ~80 kDa heavy chains (HC1 & HC2) are covalently linked to the sixth carbon of a GlcUA residue on the non-sulfated region of the CS chain, forming pre-inter-&alpha,-inhibitor (pre-I&alpha,I or P&alpha,I) with one HC. A second HC can be attached to the non-sulfated region of the CS to form I&alpha,I. I&alpha,I is known for its roles in inhibiting serine proteinases, such as plasmin, and as an HC donor for the covalent modification of hyaluronan (HA) to form HC.HA (or SHAP.HA) complexes at sites of inflammation and around the oocyte prior to ovulation. Tumor necrosis factor-stimulated gene-6 (TSG-6) forms a covalent HC.TSG-6 intermediate and subsequently transfers the HC to the sixth carbon of GlcNAc residues of HA in a transesterification reaction that contributes to the cross-linking and stabilization of HA matrices, in some contexts modification of HA with HC has been implicated in the promotion of leukocyte adhesion. In addition, the bikunin.CS chain can accept a single HC from I&alpha,I via transfer catalyzed by TSG-6 and that HCs could be swapped from bikunin.CS chain to HA. (Briggs, D.C., et al. (2015). J. Biol. Chem. 290(48):28708-28723).