Human biliary glycoprotein gene: characterization of a family of novel alternatively spliced RNAs and their expressed proteins.
Eight different human biliary glycoprotein (BGP) isoantigens, structurally related members of the carcinoembryonic antigen family, CD66/67 family, and immunoglobulin superfamily, are derived by alternative splicing from a single genomic transcription unit. Novel BGP isoforms have been identified by polymerase chain reaction amplification and by DNA sequencing of amplified cDNA segments. In addition to verifying previously documented BGPs, we describe four new forms, two of which have unusual nonimmunoglobulin exons contributed by inverted Alu repeats. Determination of the genomic DNA sequence encompassing most of the known extracellular and intracellular domains demonstrates that the translatable Alu-like sequences are encoded in bona fide exons. The third novel BGP isoform contains none of the extracellular disulfide-linked immunoglobulin-like domains typical of these molecules but retains N-terminal and intracellular domains, suggesting distinct functions for N-terminal versus other disulfide-linked domains. cDNAs coding for each identified isoform have been transfected into COS7 monkey cells, and the resulting polypeptides are heavily N glycosylated but can be deglycosylated to their expected primary sizes. Many of these deglycosylated forms can be correlated with unique patterns of BGP expression in different cell lines, while in granulocytes, some previously undescribed or alternatively modified forms may predominate. The BGP family represents a potentially large but unknown source of functional diversity among cells of epithelial and hematopoietic origin. The availability of a defined set of expressed of BGP cDNAs should permit critical definition of their function.
Barnett
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Molecular Diagnostics, Inc., West Haven, Connecticut 06516.
Drake
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Pickle
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D000595:Amino Acid Sequence; D000818:Animals; D015703:Antigens, CD; D001483:Base Sequence; D015153:Blotting, Western; D015815:Cell Adhesion Molecules; D002460:Cell Line; D003001:Cloning, Molecular; D004247:DNA; D006023:Glycoproteins / Q000235:genetics* / Q000378:metabolism; D006801:Humans; D007519:Isoantigens / Q000235:genetics; D051379:Mice; D008969:Molecular Sequence Data; D016133:Polymerase Chain Reaction; D012326:RNA Splicing; D014407:Tumor Cells, Cultured
D015703:Antigens, CD; C069847:CD66 antigens; D015815:Cell Adhesion Molecules; D006023:Glycoproteins; D007519:Isoantigens; D004247:DNA