Title : Human C1 inhibitor: primary structure, cDNA cloning, and chromosomal localization
Abstract :
- The primary structure of human C1 inhibitor was determined by peptide and DNA sequencing
- The single-chain polypeptide moiety of the intact inhibitor is 478 residues (52,869 Da), accounting for only 51% of the apparent molecular mass of the circulating protein (104,000 Da)
- The positions of six glucosamine-based and five galactosamine-based oligosaccharides were determined
- Another nine threonine residues are probably also glycosylated
- Most of the carbohydrate prosthetic groups (probably 17) are located at the amino-terminal end ( residues 1-120 ) of the protein and are particularly concentrated in a region where the tetrapeptide sequence Glx-Pro-Thr-Thr , and variants thereof, is repeated 7 times
- No phosphate was detected in C1 inhibitor
- Two disulfide bridges connect cysteine-101 to cysteine-406 and cysteine-108 to cysteine-183
- Comparison of the amino acid and cDNA sequences indicates that secretion is mediated by a 22-residue signal peptide and that further proteolytic processing does not occur
- C1 inhibitor is a member of the large serine protease inhibitor (serpin) gene family
- The homology concerns residues 120 through the C-terminus
- The sequence was compared with those of nine other serpins, and conserved and nonconserved regions correlated with elements in the tertiary structure of alpha 1-antitrypsin
- The C1 inhibitor gene maps to chromosome 11, p11 .2-q13
- C1 inhibitor genes of patients from four hereditary angioneurotic edema kindreds do not have obvious deletions or rearrangements in the C1 inhibitor locus
- A HgiAI DNA polymorphism, identified following the observation of sequence variants , will be useful as a linkage marker in studies of mutant C1 inhibitor genes