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.
mesh_terms: D000595:Amino Acid Sequence; D001483:Base Sequence; D002241:Carbohydrates / Q000032:analysis; D002874:Chromosome Mapping; D002906:Chromosomes, Human, 6-12 and X; D003001:Cloning, Molecular; D003174:Complement C1 Inactivator Proteins / Q000235:genetics* / Q000302:isolation & purification; D004247:DNA / Q000378:metabolism*; D005796:Genes; D006801:Humans; D006822:Hybrid Cells / Q000166:cytology; D008958:Models, Molecular; D009693:Nucleic Acid Hybridization; D011110:Polymorphism, Genetic; D011487:Protein Conformation
chemical_list: D002241:Carbohydrates; D003174:Complement C1 Inactivator Proteins; D004247:DNA