Open AccessInternal duplication and evolution of human ceruloplasmin.
Author(s) -
Francis E. Dwulet,
Frank W. Putnam
Publication year - 1981
Publication title -
proceedings of the national academy of sciences of the united states of america
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.011
H-Index - 771
eISSN - 1091-6490
pISSN - 0027-8424
DOI - 10.1073/pnas.78.5.2805
Subject(s) - ceruloplasmin , homology (biology) , biochemistry , amino acid , peptide sequence , gene , protein primary structure , biology , coding region , oxidoreductase , chemistry , enzyme
With the completion of the primary structure of the 50,000- and 19,000-dalton fragments of human ceruloplasmin [ferroxidase; iron(II):oxygen oxidoreductase, EC 1.16.3.1], over half of the covalent structure of the single polypeptide chain of this protein is known. Visual and computer analysis of the sequence of the 564 amino acid residues in the two fragments gives clear evidence of statistically significant internal homology suggestive of evolutionary replication of two smaller units. Two homology regions, each composed of 224 residues, were defined by an intrasequence alignment that required only three gaps in each 224-residue segment. The two homology regions exhibited 43% identity in sequence, and 13% of the remaining positions had similar residues. The sequence of a 160-residue segment in ceruloplasmin exhibits significant homology to the active (copper-binding) sites of blue electron-transfer proteins such as azurins and plastocyanins and multicopper oxidases such as cytochrome oxidase and superoxide dismutase. It is proposed that a primitive ceruloplasmin gene was formed by the fusion of two genes coding, respectively, for protein abut 160 and 190 amino acid residues in length and that this precursor gene coding for about 350 amino acids was later triplicated to form the gene for the present-day ceruloplasmin molecule of about 1050 amino acids.