Human C1 inhibitor: primary structure, cDNA cloning, and chromosomal localization

Biochemistry. 1986 Jul 29;25(15):4292-301. doi: 10.1021/bi00363a018.


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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Amino Acid Sequence
  • Base Sequence
  • Carbohydrates / analysis
  • Chromosome Mapping
  • Chromosomes, Human, 6-12 and X*
  • Cloning, Molecular*
  • Complement C1 Inactivator Proteins / genetics*
  • Complement C1 Inactivator Proteins / isolation & purification
  • DNA / metabolism*
  • Genes*
  • Humans
  • Hybrid Cells / cytology
  • Models, Molecular
  • Nucleic Acid Hybridization
  • Polymorphism, Genetic
  • Protein Conformation


  • Carbohydrates
  • Complement C1 Inactivator Proteins
  • DNA

Associated data

  • GENBANK/M13656