Department of Medicine, Mount Sinai School of Medicine, New York, New York 10029.
We have characterized the human gene encoding LBR, an integral protein of the nuclear envelope inner membrane. Restriction mapping shows that the transcription unit spans approximately 35 kilobases. A transcription start site is located approximately 4 kilobases 5' to the translation initiation codon, and an RNA splice of 3863 bases occurs in the 5'-untranslated region to generate mature HeLa cell mRNA. 5' to the identified transcription start site are two CCAAT sequences and potential recognition sites for several transcription factors including Sp1, AP-1, AP-2, and NF-kB. There are 13 protein coding exons in the LBR gene. LBR's nucleoplasmic domain is encoded by exons 1-4, and its hydrophobic domain, with eight putative transmembrane segments, is encoded by exons 5-13. The hydrophobic domain is homologous to three yeast polypeptides, suggesting that this higher eukaryotic gene could have evolved from recombination between a gene that encoded a soluble nuclear protein and a membrane protein gene similar to those in yeast. These results are the first to demonstrate the structural organization of a vertebrate gene encoding an integral membrane protein of the nuclear envelope that may be a member of a family of polypeptides conserved in evolution.