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Primary structure of bovine Hageman factor (blood coagulation factor XII): comparison with human and guinea pig
1Department of Laboratory Medicine, School of Medicine, Kumamoto University, Japan.
Insights
Researchers cloned bovine Hageman factor cDNA, revealing conserved domain structures compared to human and guinea pig factors. Differences in the proline-rich region explain why bovine Hageman factor activation differs.
Area of Science:
- Biochemistry
- Molecular Biology
- Genetics
Background:
- Hageman factor (coagulation factor XII) is a key initiator of the intrinsic pathway of blood coagulation.
- Understanding species-specific variations in Hageman factor is crucial for comparative hematology and evolutionary studies.
Purpose of the Study:
- To clone and characterize the bovine Hageman factor cDNA.
- To compare the deduced amino acid sequence and domain structure of bovine Hageman factor with those of human and guinea pig Hageman factors.
- To investigate potential reasons for differences in activation mechanisms.
Main Methods:
- Cloning of bovine Hageman factor cDNA from a liver cDNA library.
- Nucleotide sequence analysis and amino acid sequence deduction.
- Comparative sequence analysis with human and guinea pig Hageman factor primary structures.
Main Results:
- The bovine Hageman factor cDNA was successfully cloned and sequenced.
- Deduced amino acid sequence showed consistency with previously reported partial sequences.
- Putative domain structures were conserved across species, with high sequence homology (66-88% human, 63-81% guinea pig), except for the proline-rich region.
- Significant heterogeneities were observed around cleavage sites, and bovine Hageman factor lacks a suitable cleavage sequence in the proline-rich region.
Conclusions:
- Bovine Hageman factor shares conserved domain structures with human and guinea pig counterparts.
- The unique proline-rich region in bovine Hageman factor likely prevents the liberation of the activated proteinase moiety (beta-form) during activation by trypsin or plasma kallikrein.
- These findings highlight species-specific differences in Hageman factor activation pathways.
Abstract:
A bovine Hageman factor cDNA was cloned from a liver cDNA library. The nucleotide sequence was analyzed and the amino-acid sequence was deduced. The sequence deduced was consistent with the partial amino-acid sequences of bovine Hageman factor protein. The sequences for three portions including the amino terminal had been previously reported (Fujikawa et al. (1977) Biochemistry 16, 2270-2278). In comparison with the primary structures of human and guinea pig Hageman factors, the putative domain structures were totally conserved. Each domain possessed high sequence homology with the human molecule (66-88%) and the guinea pig one (63-81%) except for the proline-rich region (less than 10%) which connects the amino-terminal five domains with a serine proteinase portion. Significant heterogeneities were observed among the three species around the essential cleavage sites for the conversion to the activated Hageman factors. Bovine Hageman factor has no suitable amino-acid sequence as the substrate for the trypsin-type proteinases at the proline-rich region in difference from the human and guinea pig molecules. Probably this is the reason why the beta-form activated Hageman factor (the proteinase moiety) is not liberated in the activation of the bovine molecule with trypsin or plasma kallikrein.