Structure of human alpha 2-plasmin inhibitor deduced from the cDNA sequence.
We have isolated three cDNA clones for human alpha 2-plasmin inhibitor (alpha 2-PI). Two clones are from human hepatoma cell line, Hep G2, and cover the entire protein coding region plus the 3'-flanking region up to the poly(A) sequence, and the other clone is from human liver and contains the carboxyl-terminal half. The total length of the cDNAs is 2.29 kb, corresponding to more than 95% of the full-length mRNA. alpha 2-PI seems to consist of 452 amino acid residues plus 39 amino acid residues for the signal peptide. The amino acid sequence shows 23 to 28% homology to those of five other protease inhibitors, plasminogen activator inhibitor (PAI), protein C inhibitor (PCI), alpha 1-antitrypsin (alpha 1-AT), antithrombin III (AT III), and alpha 1-antichymotrypsin (alpha 1-AC). alpha 2-PI seems to be the most distantly related among these inhibitors. Comparison of the phylogenetic trees of proteases and their inhibitors indicates that four proteases, namely elastase (or trypsin), chymotrypsin, plasminogen activator, and thrombin, may have evolved concurrently with the corresponding inhibitors. However, alpha 2-PI and PCI seem to have evolved asynchronously from their substrates. The data suggest that alpha 2-PI may originally have inhibited some protease other than plasmin, and protein C may have had an inhibitor different from the present one early in its evolutionary history.
Tone
M
M
Basic Research Department, Hoechst Japan Limited, Saitama.
Kikuno
R
R
Kume-Iwaki
A
A
Hashimoto-Gotoh
T
T
D000595:Amino Acid Sequence; D001483:Base Sequence; D005075:Biological Evolution; D006528:Carcinoma, Hepatocellular / Q000032:analysis; D004247:DNA / Q000235:genetics* / Q000302:isolation & purification; D004274:DNA, Recombinant / Q000302:isolation & purification; D006801:Humans; D008099:Liver / Q000032:analysis; D008113:Liver Neoplasms / Q000032:analysis; D008969:Molecular Sequence Data; D008970:Molecular Weight; D009693:Nucleic Acid Hybridization; D011480:Protease Inhibitors; D012333:RNA, Messenger / Q000235:genetics; D012689:Sequence Homology, Nucleic Acid; D000979:alpha-2-Antiplasmin / Q000235:genetics*
D004274:DNA, Recombinant; D011480:Protease Inhibitors; D012333:RNA, Messenger; D000979:alpha-2-Antiplasmin; D004247:DNA