Nucleotide sequence of the rat low density lipoprotein receptor cDNA

Abstract

EMBL accession no. X13722 A 4.7 kb cDNA clone (ArLDL2-1a) coding for the rat low density lipoprotein (LDL) receptor was isolated from a Xgt-11 rat liver cDNA library (1,2). The DNA sequence of the entire coding region and portions of the 5' and 3' untranslated region is shown in Figure 1. The open reading frame coded for an 879 amino acid polypeptide with a theoretical molecular weight of 96,632, which is larger than the size of the human (3) and rabbit (4) LDL receptors. A signal sequence of 21 amino acids was also present in both the rat (Fig. 1) and human (3) receptors.

Identification and characterization of LDL receptor gene mutations in hyperlipidemic Chinese

“…Although evolutionarily conserved among human, rat, rabbit, and cow (4,(27)(28)(29), arginine 94 is not conserved among the seven cysteine-rich repeats (3). The mutation results in slower processing and delayed transport (class 2B).…”

“…The point change was not detected in our normolipidemic controls. A696G is a conservative amino acid substitution, and alanine at 696 is not conserved across species among human, rat, rabbit, and cow (4,(27)(28)(29). Although patient D162 had an elevated cholesterol value (6.77 mmol/l) in addition to hypertension, A696G is a rare sequence variation that does not affect LDL receptor function (Fig.…”

“…The novel I602V variant (EcoRV RFLP) is a conservative amino acid substitution. Isoleucine 602 is a valine at this position of rat, rabbit, and cow LDL receptor proteins (27)(28)(29). The I602V variant was found with a frequency of 1% in both normal and hyperlipidemic Chinese.…”

Dietary fatty acids regulate hepatic low density lipoprotein (LDL) transport by altering LDL receptor protein and mRNA levels.

“…By relating the rates of receptor-dependent and receptorindependent LDL uptake in the experimental animals to these normal kinetic curves, it was possible to determine how the various dietary manipulations affected LDL receptor activity (defined as the rate of receptor-dependent LDL uptake in an experimental animal relative to the rate of receptor-dependent LDL uptake seen in control animals at the same plasma LDL concentration). Determination and GAPDH (5'-AAAGGATCCACTGGCGTCTTCACCACCATG-GAG-3' and 5'-AAAGAATTCGTCATGGATGACCTTGGC-CAGGGG-3') sequences were selected from areas of 100% homology in the published rat (33) and Chinese hamster (30) Probes were synthesized as previously described (32) Samples ofhamster liver were homogenized in guanidinium isothiocyanate and the RNA was isolated by centrifugation on cesium chloride. Total RNA (40 Mg) was hybridized with the 32P-labeled cDNA probes simultaneously at 48°C overnight.…”

Rabbit very low density lipoprotein receptor: a low density lipoprotein receptor-like protein with distinct ligand specificity.

“…The LDL receptor also binds and internalizes apoE-containing lipoproteins, ,-migrating very low density lipoprotein (/3-VLDL), and a cholesterol-induced high density lipoprotein particle that contains apoE as its sole apo, with high affinity (2)(3)(4)(5). The mature LDL receptor consists of five domains (5)(6)(7)(8): (i) an N-terminal ligand-binding domain composed of seven cysteine-rich repeats (2,3), (ii) an epidermal growth factor precursor homology domain that mediates the acid-dependent dissociation of ligands (9), (iii) an 0-linked sugar domain of unknown function, (iv) a transmembrane domain, and (v) a cytoplasmic domain that mediates the clustering of the receptor into coated pits via an NPXY amino acid sequence (10).…”