Structure, chromosome location, and expression of the human very low density lipoprotein receptor gene.

Isolation and characterization of cDNAs encoding human very low density lipoprotein (VLDL) receptor revealed the presence of two forms of the receptor: one consists of five domains that resemble the low density lipoprotein (LDL) receptor, and a variant form lacks an O-linked sugar domain. More than 96% of amino acids in the human and rabbit VLDL receptors are identical, whereas those in the LDL receptors are less conserved between the two species (76%). The human VLDL receptor gene contains 19 exons spanning approximately 40 kilobases. The exon-intron organization of the gene is almost the same as that of the LDL receptor gene, except for an extra exon that encodes an additional repeat in the ligand binding domain of the VLDL receptor. Analysis of DNA from human-rodent hybrid cells revealed that the gene is located on chromosome 9. Although the 5'-flanking region of the VLDL receptor gene contains two copies of a sterol regulatory element-1 like sequence, the levels of mRNA for the receptor in THP-1 human monocytic leukemia cells were unchanged by sterols. The 5'-untranslated region of the receptor mRNA contains a polymorphic triplet repeat found also in the fragile X syndrome gene.