OLR1

Oxidized low-density lipoprotein receptor 1 (Ox-LDL receptor 1) also known as lectin-type oxidized LDL receptor 1 (LOX-1) is a protein that in humans is encoded by the OLR1 gene.^[5][6]

OLR1
Available structures PDB Ortholog search: PDBe RCSB List of PDB id codes 1YPO, 1YPQ, 1YPU, 1YXJ, 1YXK, 3VLG
Identifiers
Aliases	OLR1, CLEC8A, LOX1, LOXIN, SCARE1, SLOX1, oxidized low density lipoprotein receptor 1
External IDs	OMIM: 602601; MGI: 1261434; HomoloGene: 1910; GeneCards: OLR1; OMA:OLR1 - orthologs
Gene location (Human) Chr. Chromosome 12 (human)[1] Band 12p13.2 Start 10,158,301 bp[1] End 10,172,138 bp[1]
Gene location (Mouse) Chr. Chromosome 6 (mouse)[2] Band 6|6 F3 Start 129,462,207 bp[2] End 129,484,128 bp[2]
RNA expression pattern Bgee Human Mouse (ortholog) Top expressed in right lung C1 segment bone marrow cells upper lobe of left lung lower lobe of lung placenta corpus callosum testicle appendix gallbladder Top expressed in gastrula decidua granulocyte right lung lobe embryo tibiofemoral joint primordial ventricle blastocyst uterus bone marrow More reference expression data BioGPS More reference expression data
Gene ontology Molecular function protein binding carbohydrate binding identical protein binding Cellular component integral component of membrane membrane intracellular membrane-bounded organelle receptor complex plasma membrane integral component of plasma membrane nucleoplasm extracellular region membrane raft specific granule membrane tertiary granule membrane Biological process immune system process blood circulation proteolysis cell adhesion inflammatory response leukocyte migration neutrophil degranulation Sources:Amigo / QuickGO
Orthologs Species Human Mouse Entrez 4973 108078 Ensembl ENSG00000173391 ENSMUSG00000030162 UniProt P78380 Q9EQ09 RefSeq (mRNA) NM_001172632 NM_001172633 NM_002543 NM_001301094 NM_001301096 NM_138648 RefSeq (protein) NP_001166103 NP_001166104 NP_002534 NP_001288023 NP_001288025 NP_619589 Location (UCSC) Chr 12: 10.16 – 10.17 Mb Chr 6: 129.46 – 129.48 Mb PubMed search [3] [4]
Wikidata
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LOX-1 is the main receptor for oxidized LDL on endothelial cells, macrophages, smooth muscle cells,^[7] and other cell types.^[8] But minimally oxidized LDL is more readily recognized by the TLR4 receptor, and highly oxidized LDL is more readily recognized by the CD36 receptor.^[9]

Function

LOX-1 is a receptor protein which belongs to the C-type lectin superfamily. Its gene is regulated through the cyclic AMP signaling pathway. The protein binds, internalizes and degrades oxidized low-density lipoprotein.^{[citation needed]}

Normally, LOX-1 expression on endothelial cells is low, but tumor necrosis factor alpha, oxidized LDL, blood vessel shear stress, and other atherosclerotic stimuli substantially increase LOX-1 expression.^[8][10]

LOX-1 may be involved in the regulation of Fas-induced apoptosis. Oxidized LDL induces endothelial cell apoptosis through LOX-1 binding.^[7] Other ligands for LOX-1 include oxidized high-density lipoprotein, advanced glycation end-products, platelets, and apoptotic cells.^[7][10] The binding of platelets to LOX-1 causes a release of vasoconstrictive endothelin, which induces endothelial dysfunction.^[10]

This protein may play a role as a scavenger receptor.^[6]

Clinical significance

Binding of oxidized LDL to LOX-1 activates NF-κB, leading to monocyte adhesion to enthothelial cells (a pre-requisite for the macrophage foam cell formation of atherosclerosis).^[8] Macrophage affinity for unmodified LDL particles is low, but is greatly increased when the LDL particles are oxidized.^[11] LDL oxidation occurs in the sub-endothelial space, rather than in the circulation.^[11] But oxidized cholesterol from foods cooked at high temperature can also be a source of oxysterols.^[9]

Mutations of the OLR1 gene have been associated with atherosclerosis, risk of myocardial infarction, and may modify the risk of Alzheimer's disease.^[6] When applied to human macrophage-derived foam cells in vitro, the dietary supplement berberine inhibits the expression of the ORL1 gene in response to oxidized low-density lipoprotein cholesterol,^[12] but this has not yet been demonstrated in a living animal or human.^{[citation needed]}