The low-density lipoprotein receptor (LDL-R) is a mosaic protein of 839 amino acids (after removal of 21-amino acid signal peptide)[5] that mediates the endocytosis of cholesterol-rich low-density lipoprotein (LDL). It is a cell-surface receptor that recognizes apolipoprotein B100 (ApoB100), which is embedded in the outer phospholipid layer of very low-density lipoprotein (VLDL), their remnants—i.e. intermediate-density lipoprotein (IDL), and LDL particles. The receptor also recognizes apolipoprotein E (ApoE) which is found in chylomicron remnants and IDL. In humans, the LDL receptor protein is encoded by the LDLR gene on chromosome 19.[6][7][8] It belongs to the low density lipoprotein receptor gene family.[9] It is most significantly expressed in bronchial epithelial cells and adrenal gland and cortex tissue.[10]
Michael S. Brown and Joseph L. Goldstein were awarded the 1985 Nobel Prize in Physiology or Medicine for their identification of LDL-R[11] and its relation to cholesterol metabolism and familial hypercholesterolemia.[12] Disruption of LDL-R can lead to higher LDL-cholesterol as well as increasing the risk of related diseases. Individuals with disruptive mutations (defined as nonsense, splice site, or indel frameshift) in LDLR have an average LDL-cholesterol of 279 mg/dL, compared with 135 mg/dL for individuals with neither disruptive nor deleterious mutations. Disruptive mutations were 13 times more common in individuals with early-onset myocardial infarction or coronary artery disease than in individuals without either disease.[13]
- ^ a b c GRCh38: Ensembl release 89: ENSG00000130164 – Ensembl, May 2017
- ^ a b c GRCm38: Ensembl release 89: ENSMUSG00000032193 – Ensembl, May 2017
- ^ "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
- ^ "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
- ^ Südhof TC, Goldstein JL, Brown MS, Russell DW (May 1985). "The LDL receptor gene: a mosaic of exons shared with different proteins". Science. 228 (4701): 815–22. Bibcode:1985Sci...228..815S. doi:10.1126/science.2988123. PMC 4450672. PMID 2988123.
- ^ Francke U, Brown MS, Goldstein JL (May 1984). "Assignment of the human gene for the low density lipoprotein receptor to chromosome 19: synteny of a receptor, a ligand, and a genetic disease". Proceedings of the National Academy of Sciences of the United States of America. 81 (9): 2826–30. Bibcode:1984PNAS...81.2826F. doi:10.1073/pnas.81.9.2826. PMC 345163. PMID 6326146.
- ^ Lindgren V, Luskey KL, Russell DW, Francke U (December 1985). "Human genes involved in cholesterol metabolism: chromosomal mapping of the loci for the low density lipoprotein receptor and 3-hydroxy-3-methylglutaryl-coenzyme A reductase with cDNA probes". Proceedings of the National Academy of Sciences of the United States of America. 82 (24): 8567–71. Bibcode:1985PNAS...82.8567L. doi:10.1073/pnas.82.24.8567. PMC 390958. PMID 3866240.
- ^ "LDLR low density lipoprotein receptor [Homo sapiens (human)] - Gene - NCBI". www.ncbi.nlm.nih.gov. Retrieved 2016-10-10.
- ^ Nykjaer A, Willnow TE (June 2002). "The low-density lipoprotein receptor gene family: a cellular Swiss army knife?". Trends in Cell Biology. 12 (6): 273–80. doi:10.1016/S0962-8924(02)02282-1. PMID 12074887.
- ^ "BioGPS - your Gene Portal System". biogps.org. Retrieved 2016-10-10.
- ^ "The Nobel Prize in Physiology or Medicine 1985" (Press release). The Royal Swedish Academy of Science. 1985. Retrieved 2010-07-01.
- ^ Brown MS, Goldstein JL (November 1984). "How LDL receptors influence cholesterol and atherosclerosis". Scientific American. 251 (5): 58–66. Bibcode:1984SciAm.251c..52K. doi:10.1038/scientificamerican0984-52. PMID 6390676.
- ^ Do R, Stitziel NO, Won HH, Jørgensen AB, Duga S, Angelica Merlini P, et al. (February 2015). "Exome sequencing identifies rare LDLR and APOA5 alleles conferring risk for myocardial infarction". Nature. 518 (7537): 102–6. Bibcode:2015Natur.518..102.. doi:10.1038/nature13917. PMC 4319990. PMID 25487149.