Structure of the human APO-1 gene.
APO-1/Fas (CD95) is a type 1 transmembrane protein that belongs to the tumor necrosis factor/nerve growth factor receptor family characterized by cysteine-rich extracellular domains. Cross-linking of APO-1 mediates apoptosis in a variety of cells. In the present study we report the isolation and characterization of the human APO-1 gene spanning approximately 25 kb of human chromosome 10. The gene consists of nine exons (25 bp to > 1.44 kb) separated by eight introns (152 bp to approximately 12 kb). The boundaries of exon 2 to 5 encoding the extracellular region do not match the boundaries of the three APO-1 protein subdomains. Exon structure and functional protein domains correspond for exon 6 encoding the transmembrane region and for exon 9 encoding the "death domain". By a polymerase chain reaction-based approach we localized major transcriptional start sites in human spleen cells 77 and 73 nucleotides upstream of the translation initiation codon of the human APO-1 gene. Minor initiation sites were found at positions -128, -111, -91, and -74. The 5' flanking sequence of the human APO-1 gene is GC rich, contains a high number of CpG dinucleotides and lacks a consensus TATA box. Consensus binding sites for the transcription factors Sp1, AP-1, AP-2, GAF, NF-kappa B, and NF-AT were found. The elucidation of the human APO-1 gene structure will facilitate the study of its involvement in various diseases such as in autoimmunity.
Behrmann
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Tumorimmunology Program/Division of Immunogenetics, German Cancer Research Center, Heidelberg.
Walczak
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H
Krammer
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PH
D000595:Amino Acid Sequence; D000954:Antigens, Surface / Q000235:genetics*; D001483:Base Sequence; D001665:Binding Sites; D003001:Cloning, Molecular; D005786:Gene Expression Regulation; D005796:Genes; D006801:Humans; D008969:Molecular Sequence Data; D011401:Promoter Regions, Genetic; D012326:RNA Splicing; D012333:RNA, Messenger / Q000235:genetics; D015183:Restriction Mapping; D014157:Transcription Factors / Q000378:metabolism; D014158:Transcription, Genetic; D019014:fas Receptor
D000954:Antigens, Surface; D012333:RNA, Messenger; D014157:Transcription Factors; D019014:fas Receptor