Completion of the primary structure of human high-molecular-mass kininogen. The amino acid sequence of the entire heavy chain and evidence for its evolution by gene triplication.

The amino acid sequence of the heavy chain of human high-molecular-mass kininogen has been determined. It completes the primary structure of the high-Mr kininogen molecule. The heavy chain contains 362, the total kininogen molecule 626 amino acid residues. Three carbohydrate side chains were found in the heavy chain, all of them N-glycosidically linked to asparagine, which is present in the acceptor sequon Asn-Xaa-Thr (or -Ser); one additional potential glycosylation site devoid of a sugar side chain is found at position 30. There is a high degree of homology between the heavy chains of human high-Mr kininogen and bovine high-Mr kininogen (74% identity), or rat T-kininogen (61%). Comparison of the primary structure of human high-Mr kininogen with that of human low-Mr kininogen predicted from its cDNA sequence, reveals that the heavy chains of the two human kininogens are completely identical. Two heavy chain segments believed to contain the reactive sites for cysteine proteinase inhibition show an extensive sequence homology with other mammalian cysteine proteinase inhibitors. Within the heavy chain of human high-Mr kininogen are repetitive units strongly suggesting that the heavy chain of human kininogens has evolved from at least two ancestral units by a series of gene duplication and fusion events.