title: The 56K autoantigen is identical to human annexin XI.
abstract: Anti-56K autoantibodies are present in sera from patients with various autoimmune diseases, predominantly in sera from patients with rheumatoid arthritis, systemic lupus erythematosus, or Sjögren's syndrome. To clarify the molecular structure of this autoantigen, we isolated a 2.0-kilobase pair cDNA clone considered to encode the full-length 56K autoantigen. The longest open reading frame encodes a 505-amino acid polypeptide, with a predicted molecular mass of 54.4 kDa. The in vitro translated protein is recognized by all anti-56K positive patient sera tested. Antibodies affinity-purified using the bacterially expressed recombinant protein recognized the 56K autoantigen in a HeLa cell extract. cDNA sequencing revealed that the 56K cDNA shares a high degree of homology in both nucleotide (87%) and amino acid sequence (92.5%) with bovine annexin XI, indicating that the 56K cDNA encodes the human homologue of annexin XI, a member of the Ca(2+)-dependent phospholipid binding protein family. Anti-56K autoantibody exhibits both a cytoplasmic and a nuclear staining in immunofluorescence experiments. Patients' sera recognize preferentially the N-terminal region of the protein, which is specific for 56K/annexin XI and not shared by other annexins, indicating that the autoimmune response to 56K/annexin XI in these patients is specific for this annexin family member.
authors.affiliation: Department of Biochemistry, University of Nijmegen, The Netherlands.
authors.forename: Y
authors.initials: Y
authors.lastname: Misaki
authors.forename: G J
authors.initials: GJ
authors.lastname: Pruijn
authors.forename: A W
authors.initials: AW
authors.lastname: van der Kemp
authors.forename: W J
authors.initials: WJ
authors.lastname: van Venrooij
mesh_terms: D000595:Amino Acid Sequence; D017302:Annexins / Q000235:genetics / Q000276:immunology*; D001324:Autoantigens / Q000737:chemistry* / Q000235:genetics; D001402:B-Lymphocytes / Q000276:immunology; D001483:Base Sequence; D002451:Cell Compartmentation; D003001:Cloning, Molecular; D017931:DNA Primers / Q000737:chemistry; D018076:DNA, Complementary; D000939:Epitopes; D005455:Fluorescent Antibody Technique; D008969:Molecular Sequence Data; D015183:Restriction Mapping; D016415:Sequence Alignment; D017384:Sequence Deletion; D017386:Sequence Homology, Amino Acid; D013329:Structure-Activity Relationship
chemical_list: D017302:Annexins; D001324:Autoantigens; D017931:DNA Primers; D018076:DNA, Complementary; D000939:Epitopes