AMBP Gene: Alpha-1-Microglobulin/Bikunin Precursor – Function, Mutations, and Disease Associations

The AMBP gene encodes a precursor protein that is proteolytically cleaved into two distinct functional proteins: alpha-1-microglobulin (A1M) and bikunin. Alpha-1-microglobulin is a heme-binding and antioxidant protein involved in heme scavenging, immunomodulation, and tissue protection. Bikunin is a serine protease inhibitor (Kunitz-type) that inhibits trypsin, plasmin, and other proteases, playing roles in inflammation, extracellular matrix remodeling, and cancer. The gene is primarily expressed in the liver and secreted into the blood.

Tissue Expression

Cell Line Expression

Hotspot Mutations

Mutation functional classification

• KEGG hsa04610 – Complement and coagulation cascades (bikunin as inhibitor)

• Reactome R-HSA-1474228 – Degradation of the extracellular matrix (bikunin inhibits uPA)

• Reactome R-HSA-6798695 – Neutrophil degranulation (A1M involved in heme scavenging)

The AMBP gene product is a 352-amino-acid precursor protein (UniProt P02760) that is cleaved into alpha-1-microglobulin (A1M, 183 residues) and bikunin (147 residues). A1M is a 26-kDa glycoprotein with heme-binding and reductase activities, protecting cells from oxidative damage. Bikunin is a 16-kDa Kunitz-type serine protease inhibitor that inhibits trypsin, plasmin, and uPA, thereby regulating fibrinolysis, inflammation, and tumor invasion. Both proteins are secreted and circulate in plasma.