Exon/Intron Organization, Chromosome Localization, Alternative Splicing, and Transcription Units of the Human Apolipoprotein E Receptor 2 Gene

Apolipoprotein E receptor 2 is a recently identified receptor that resembles low and very low density lipoprotein receptors. Isolation and characterization of genomic clones encoding human apolipoprotein E receptor 2 revealed that the gene spans ~60 kilobases and contains 19 exons. The positions of the exon/intron boundaries of the gene are almost identical to those of low and very low density lipoprotein receptors. Fluorescent in situ hybridization of human chromosomes revealed that the gene is located on chromosome 1p34. Isolation of a cDNA encoding a variant receptor and reverse transcription-polymerase chain reaction indicate the presence of multiple variants with different numbers of cysteine-rich repeats in the binding domain of the receptor. We also found a variant receptor lacking a 59-amino acid insertion in the cytoplasmic domain. The transcription start site was mapped to the position 236 base pairs upstream of the AUG translation initiator codon by primer extension analysis. Sequence inspection of the 5′-flanking region revealed potential DNA elements: AP-2, GC factor, PEA3, and Sp1. The minimal promoter region and a region required for nerve growth factor inducibility in PC12 cells were also determined.