CLONING AND CHARACTERIZATION OF THE GENE ENCODING HUMAN OSTEOPROTEGERIN OSTEOCLASTOGENESIS-INHIBITORY FACTOR/

The human osteoprotegerin (OPG)-osteoclastogenesis-inhibitory factor ( OCIF) gene has been cloned and characterized. The OPG-OCIF gene is a s ingle-copy gene consisting of five exons, and spans 29 kb of the human genome. All the exon/intron boundaries comply with the GT/AG rule. Th e translation-termination codon is present in exon 5 and a typical pol y(A)-addition signal resides 173-nucleotides downstream of the transla tion-termination codon. A major transcription-initiation site is prese nt 67-nucleotides upstream of the initiation ATG codon. Two minor site s are present further upstream. The 4.2-kb and 6.5-kb transcripts dete cted in IMR-90 cells were found to contain the 3'-half of intron 2 and the entire intron 2, respectively. In the OPG-OCIF gene, a single int ron divides the stretch that encode four Cys-rich motifs, implying div ersity from the other members of the tumor necrosis factor receptor (T NFR) family. Two death domain homologous regions (DDHs) present in tan dem in OPG-OCIF are encoded separately by exons 4 and 5. The conservat ion of amino-acid sequences suggests that exon 4 is produced by a dupl ication of a portion of exon 5.