Covalent structure of human haptoglobin: a serine protease homolog.
The complete amino acid sequences and the disulfide arrangements of the two chains of human haptoglobin 1-1 were established. The alpha 1 and beta chains of haptoglobin contain 83 and 245 residues, respectively. Comparison of the primary structure of haptoglobin with that of the chymotrypsinogen family of serine proteases revealed a significant degree of chemical similarity. The probability was less than 10(-5) that the chemical similarity of the beta chain of haptoglobin to the proteases was due to chance. The amino acid sequence of the beta chain of haptoglobin is 29--33% identical to bovine trypsin, bovine chymotrypsin, porcine elastase, human thrombin, or human plasmin. Comparison of haptoglobin alpha 1 chain to activation peptide regions of the zymogens revealed an identity of 25% to the fifth "kringle" region of the activation peptide of plasminogen. The probability was less than 0.014 that this similarity was due to chance. These results strongly indicate haptoglobin to be a homolog of the chymotrypsinogen family of serine proteases. Alignment of the beta-chain sequence of haptoglobin to the serine proteases is remarkably consistent except for an insertion of 16 residues in the region corresponding to the methionyl loop of the serine proteases. The active-site residues typical of the serine proteases, histidine-57 and serine-195, are replaced in haptoglobin by lysine and alanine, respectively; however, aspartic acid-102 and the trypsin specificity, residue, aspartic acid-189, do occur in haptoglobin. Haptoglobin and the serine proteases represent a striking example of homologous proteins with different biological functions.
D000595:Amino Acid Sequence; D000818:Animals; D002417:Cattle; D002918:Chymotrypsin / Q000235:genetics; D002919:Chymotrypsinogen / Q000235:genetics; D003201:Computers; D005170:Factor X / Q000235:genetics; D006242:Haptoglobins / Q000235:genetics; D006801:Humans; D010196:Pancreatic Elastase / Q000235:genetics; D010446:Peptide Fragments; D010447:Peptide Hydrolases / Q000235:genetics*; D010802:Phylogeny; D010958:Plasminogen / Q000235:genetics; D011487:Protein Conformation; D011516:Prothrombin / Q000235:genetics; D014357:Trypsin / Q000235:genetics; D014362:Trypsinogen / Q000235:genetics
D006242:Haptoglobins; D010446:Peptide Fragments; D011516:Prothrombin; D005170:Factor X; D010958:Plasminogen; D014362:Trypsinogen; D002919:Chymotrypsinogen; D010447:Peptide Hydrolases; D002918:Chymotrypsin; D010196:Pancreatic Elastase; D014357:Trypsin