Human bullous pemphigoid antigen (BPAG1). Amino acid sequences deduced from cloned cDNAs predict biologically important peptide segments and protein domains.
Bullous pemphigoid antigens are defined as the autoantigens in a blistering skin disease, bullous pemphigoid. One of them, a 230-kDa protein (BPAG1), is associated with hemidesmosomes, attachment complexes at the basal keratinocyte-lamina lucida interface within the dermal-epidermal basement membrane zone. The precise functions and cellular compartmentalization of BPAG1 are unknown. In this study, a human keratinocyte lambda gt11 cDNA library was screened for clones corresponding to BPAG1. The composite of overlapping cDNAs delineated 8,930 base pairs of nucleotide sequences that contained an open reading frame encoding 2,649 amino acids. Analysis of the deduced amino acid sequences predicted a putative signal peptide of 43 amino acids and the presence of a membrane-associated sequence of 17 amino acids. Several potential sites for N-glycosylation, as well as for protein kinase C or cAMP- and cGMP-dependent protein kinase-mediated phosphorylation were identified. Three peptide segments were predicted to be highly antigenic, potentially serving as epitopes for the formation of autoantibodies. Eight repeat segments of 38 residues each with a high degree of homology with sequences in desmoplakin I, a component of desmosomal cytoplasmic plaques, were detected in the carboxyl-terminal end of the molecule. In addition, the presence of three subdomains characterized by heptad repeats predicted an alpha-helical coiled coil dimer structure in the central portion of the protein. These data suggest that BPAG1 may be a membrane-associated protein that plays a role in the attachment of basal keratinocytes to the underlying basement membrane.
Sawamura
D
D
Department of Dermatology, Jefferson Medical College, Thomas Jefferson University, Philadelphia, Pennsylvania 19107.
Li
K
K
Chu
M L
ML
Uitto
J
J
D000595:Amino Acid Sequence; D001324:Autoantigens / Q000235:genetics*; D001483:Base Sequence; D015152:Blotting, Northern; D002352:Carrier Proteins; D003001:Cloning, Molecular; D003094:Collagen; D003598:Cytoskeletal Proteins; D004247:DNA / Q000235:genetics; D000071821:Dystonin; D000939:Epitopes / Q000235:genetics; D006801:Humans; D015603:Keratinocytes / Q000737:chemistry; D008969:Molecular Sequence Data; D009419:Nerve Tissue Proteins; D024041:Non-Fibrillar Collagens; D016366:Open Reading Frames; D010446:Peptide Fragments / Q000235:genetics* / Q000378:metabolism; D012313:RNA / Q000032:analysis; D012091:Repetitive Sequences, Nucleic Acid; D015183:Restriction Mapping; D016415:Sequence Alignment; D000097805:Collagen Type XVII
D001324:Autoantigens; D002352:Carrier Proteins; D003094:Collagen; D003598:Cytoskeletal Proteins; D004247:DNA; D000071821:Dystonin; D000939:Epitopes; D009419:Nerve Tissue Proteins; D024041:Non-Fibrillar Collagens; D010446:Peptide Fragments; D012313:RNA; D000097805:Collagen Type XVII; C486268:DST protein, human