LDLR low-density lipoprotein receptor
Molecule TypeAntigen ExpressionMolecular Weight
Min / Max
Non-lineage Restricted Molecule
Type 1 glycoprotein
Cortex, Adrenal
155 / 165

The LDLR, a low density lipoprotein receptor, is found in most tissues with the highest levels of expression on hepatocytes and in the adrenal cortex.  It is also present on lymphocytes, monocytes and macrophages.  The LDLR is regulated by cholesterol levels, such that cells incubated in a cholesterol-free media upregulate LDLR expression the addition of LDL or cholesterol which can lead to a decrease in receptor expression.

The LDLR is a single chain type 1 glycoprotein.  The LDLR protein is comprised of several functional domains.  The N-terminal 288 aa of the protein contains 7 Cys-rich repeats called LDLR domains.  This region of the protein was shown to be important for the ligand binding function of the receptor by mutagenesis studies.  The next 350 aa show a 33% homology to the EGF precursor and includes 3 EGF domains. The intron/exon boundaries for the EGF domains are preserved between the EGF precursor and the LDLR.  The 1st EGF domain participates in ligand binding, and it has also been shown that this entire region is important for the dissociation of ligand from receptor in an intracellular acidic compartment.  The membrane-proximal regions contains sites for O-linked carbohydrate attachment.  The cytoplasmic domain contains a short motif, based around Tyr807, which serves to localize the receptor into coated pits and to mediate internalization.  This short motif is postulated to form a tight turn, similar to a sequence in the intracellular domain of the transferrin receptor, CD71.  The N-terminal protein sequence has been determined for the purified bovine receptor, which is very similar to the human protein.

Cell Type Unreduced Reduced
160 kDa

The LDLR binds apoB-100- and apoE-containing lipoprotein particles. The receptor-ligand complex is internalized in coated pits, and the ligand dissociates from the receptor in acidic endosomes. The free LDLR is then recycled to the cell surface.

The LDLR delivers cholesterol-containing lipoproteins to cells for use in membrane biogenesis, synthesis of bile acids and steroid hormone synthesis.  The ability of receptor levels to be increased on activated macrophages may contribute to foam cell formation and generation of atherosclerotic plaques. Transgenic mice overexpressing human LDLR clear intravenously injected LDL 8-10 times more rapidly than normal mice, while their plasma concentrations of apoB-100 and apoE are reduced by greater than 90%.

Naturally occurring mutations which affect human LDLR expression, ligand binding, or internalization lead to familial hypercholesterolemia which is characterized by high blood cholesterol levels and myocardial infarction or atherosclerosis early in life.

Database accession numbers

Revised June 25, 2008

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