Low-density lipoprotein receptor
GeneName
LDLR
Summary
LDLR, also known as the low density lipoprotein receptor, is a 95kDa membrane protein predominantly expressed in the liver, but also found in other tissues such as the brain and adrenal glands. It is localised to various cellular compartments including the plasma membrane, early and late endosomes, and lysosomes. LDLR plays a critical role in cholesterol homeostasis by mediating the endocytosis of low-density lipoprotein (LDL) particles, thus regulating lipid metabolism. It binds to lipoprotein particles, including LDL and very-low-density lipoproteins, facilitating their uptake by cells. Additionally, LDLR is involved in amyloid-beta clearance, which links it to neurodegenerative processes. The receptor also interacts with various proteins, including clathrin, and forms complexes that are essential for its function in endocytosis and lipid transport.
Importance
LDLR is relevant to: - Cholesterol metabolism and cardiovascular health due to its role in regulating LDL levels in the bloodstream - Neurodegenerative diseases, particularly Alzheimer’s, through its involvement in amyloid-beta clearance - Metabolic disorders related to dyslipidaemia and obesity, as it influences lipid uptake and storage - Drug development targeting lipid-related diseases, given its potential as a therapeutic target for cholesterol-lowering treatments
Top Products
For researchers investigating LDLR, we highly recommend the top-selling recombinant antibody, Anti-LDL Receptor antibody [EP1553Y] (ab52818). This well-cited antibody has garnered 176 citations, reflecting its strong reputation in the field. It has been validated in knockout models, ensuring reliable performance in various applications, particularly in Western blotting (WB) and immunohistochemistry (IHC). This antibody is an excellent choice for those seeking consistent and effective detection of LDLR in their studies. The Human LDLR ELISA Kit (ab270212) is an excellent option for researchers looking to measure LDLR levels in their samples.
Abcam Product Citation Summary
The data indicates a significant focus on the LDLR target in various biological contexts, particularly in studies related to cholesterol metabolism and homeostasis. The use of different species, including human and mouse models, highlights the relevance of LDLR in both basic research and potential therapeutic applications. The predominant application of Western blotting suggests a strong interest in protein expression and regulation associated with LDLR.
Abcam Product Citation Table
Domain
The NPXY motif mediates the interaction with the clathrin adapter DAB2 and with LDLRAP1 which are involved in receptor internalization. A few residues outside the motif also play a role in the interaction.
Function
Binds low density lipoprotein /LDL, the major cholesterol-carrying lipoprotein of plasma, and transports it into cells by endocytosis. In order to be internalized, the receptor-ligand complexes must first cluster into clathrin-coated pits. Forms a ternary complex with PGRMC1 and TMEM97 receptors which increases LDLR-mediated LDL internalization (PubMed:30443021).
(Microbial infection) Acts as a receptor for hepatitis C virus in hepatocytes, but not through a direct interaction with viral proteins.
(Microbial infection) Acts as a receptor for Vesicular stomatitis virus.
(Microbial infection) In case of HIV-1 infection, may function as a receptor for extracellular Tat in neurons, mediating its internalization in uninfected cells.
(Microbial infection) Acts as a receptor for Crimean-Congo hemorrhagic fever virus (CCHFV).
(Microbial infection) Acts as a receptor for many Alphavirus, including Getah virus (GETV), Ross river virus (RRV) and Semliki Forest virus.
Involvement in disease
Hypercholesterolemia, familial, 1
FHCL1
A form of hypercholesterolemia, a disorder of lipoprotein metabolism characterized by elevated serum low-density lipoprotein (LDL) cholesterol levels, which result in excess deposition of cholesterol in tissues and leads to xanthelasma, xanthomas, accelerated atherosclerosis and increased risk of premature coronary heart disease. FHCL1 inheritance is autosomal dominant.
None
The disease is caused by variants affecting the gene represented in this entry.
Post-translational modifications
N- and O-glycosylated.
Ubiquitinated by MYLIP leading to degradation.
Sequence Similarities
Belongs to the LDLR family.
Cellular localization
- Cell membrane
- Single-pass type I membrane protein
- Membrane
- Clathrin-coated pit
- Golgi apparatus
- Early endosome
- Late endosome
- Lysosome
- Rapidly endocytosed upon ligand binding. Localized at cell membrane, probably in lipid rafts, in serum-starved conditions (PubMed:30443021).
Alternative names
Low-density lipoprotein receptor, LDL receptor, LDLR