OLR1

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
View/Edit Human View/Edit Mouse

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]

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]

References

1. GRCh38: Ensembl release 89: ENSG00000173391 – Ensembl, May 2017
2. GRCm38: Ensembl release 89: ENSMUSG00000030162 – Ensembl, May 2017
3. "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
4. "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
5. Li X, Bouzyk MM, Wang X (Nov 1998). "Assignment of the human oxidized low-density lipoprotein receptor gene (OLR1) to chromosome 12p13.1→p12.3, and identification of a polymorphic CA-repeat marker in the OLR1 gene". Cytogenet Cell Genet. 82 (1–2): 34–6. doi:10.1159/000015059. PMID 9763655. S2CID 46772688.
6. "Entrez Gene: OLR1 oxidized low density lipoprotein (lectin-like) receptor 1".
7. Pirillo A, Norata GD, Catapano AL (2013). "LOX-1, OxLDL, and atherosclerosis". Mediators of Inflammation. 2013: 1–12. doi:10.1155/2013/152786. PMC 3723318. PMID 23935243.
8. Xu S, Ogura S, Chen J, Little PJ, Moss J, Liu P (2013). "LOX-1 in atherosclerosis: biological functions and pharmacological modifiers". Cellular and Molecular Life Sciences. 70 (16): 2859–2872. doi:10.1007/s00018-012-1194-z. PMC 4142049. PMID 23124189.
9. Zmysłowski A, Szterk A (2017). "Current knowledge on the mechanism of atherosclerosis and pro-atherosclerotic properties of oxysterols". Lipids in Health and Disease. 16 (1): 188. doi:10.1186/s12944-017-0579-2. PMC 5625595. PMID 28969682.
10. Kakutani M, Masaki T, Sawamura T (2000). "A platelet-endothelium interaction mediated by lectin-like oxidized low-density lipoprotein receptor-1". Proceedings of the National Academy of Sciences of the United States of America. 97 (1): 360–364. Bibcode:2000PNAS...97..360K. doi:10.1016/j.biochi.2016.10.010. PMC 26668. PMID 10618423.
11. Brites F, Martin M, Guillas I, Kontush A (2017). "Antioxidative activity of high-density lipoprotein (HDL): Mechanistic insights into potential clinical benefit". BBA Clinical. 8: 66–77. doi:10.1016/j.bbacli.2017.07.002. PMC 5597817. PMID 28936395.
12. Guan S, Wang B, Li W, Guan J, Fang X (2010). "Effects of berberine on expression of LOX-1 and SR-BI in human macrophage-derived foam cells induced by ox-LDL". Am J Chin Med. 38 (6): 1161–9. doi:10.1142/s0192415x10008548. PMID 21061468.

Further reading

• Sawamura T (2002). "[Molecular identification of LOX-1 and analysis of its pathophysiological role]". Nippon Yakurigaku Zasshi. 119 (3): 145–54. doi:10.1254/fpj.119.145. PMID 11915516.
• Mehta JL, Li D (2002). "Identification, regulation and function of a novel lectin-like oxidized low-density lipoprotein receptor". J. Am. Coll. Cardiol. 39 (9): 1429–35. doi:10.1016/S0735-1097(02)01803-X. PMID 11985903.
• Sawamura T (2002). "[LOX-1: the oxidized LDL receptor expressed in vascular endothelial cells]". Seikagaku. 74 (5): 365–76. PMID 12073608.
• Ando K, Fujita T (2005). "Role of lectin-like oxidized low-density lipoprotein receptor-1 (LOX-1) in the development of hypertensive organ damage". Clin. Exp. Nephrol. 8 (3): 178–82. doi:10.1007/s10157-004-0288-9. PMID 15480893. S2CID 24851728.
• Sawamura T, Kume N, Aoyama T, et al. (1997). "An endothelial receptor for oxidized low-density lipoprotein". Nature. 386 (6620): 73–7. Bibcode:1997Natur.386...73S. doi:10.1038/386073a0. PMID 9052782. S2CID 4321933.
• Yoshida H, Kondratenko N, Green S, et al. (1998). "Identification of the lectin-like receptor for oxidized low-density lipoprotein in human macrophages and its potential role as a scavenger receptor". Biochem. J. 334 (Pt 1) (Pt 1): 9–13. doi:10.1042/bj3340009. PMC 1219654. PMID 9693095.
• Mehta JL, Li DY (1998). "Identification and autoregulation of receptor for OX-LDL in cultured human coronary artery endothelial cells". Biochem. Biophys. Res. Commun. 248 (3): 511–4. doi:10.1006/bbrc.1998.9004. PMID 9703956.
• Yamanaka S, Zhang XY, Miura K, et al. (1999). "The human gene encoding the lectin-type oxidized LDL receptor (OLR1) is a novel member of the natural killer gene complex with a unique expression profile". Genomics. 54 (2): 191–9. doi:10.1006/geno.1998.5561. PMID 9828121.
• Nagase M, Abe J, Takahashi K, et al. (1999). "Genomic organization and regulation of expression of the lectin-like oxidized low-density lipoprotein receptor (LOX-1) gene". J. Biol. Chem. 273 (50): 33702–7. doi:10.1074/jbc.273.50.33702. PMID 9837956.
• Draude G, Hrboticky N, Lorenz RL (1999). "The expression of the lectin-like oxidized low-density lipoprotein receptor (LOX-1) on human vascular smooth muscle cells and monocytes and its down-regulation by lovastatin". Biochem. Pharmacol. 57 (4): 383–6. doi:10.1016/S0006-2952(98)00313-X. PMID 9933026.
• Aoyama T, Sawamura T, Furutani Y, et al. (1999). "Structure and chromosomal assignment of the human lectin-like oxidized low-density-lipoprotein receptor-1 (LOX-1) gene". Biochem. J. 339 (Pt 1) (Pt 1): 177–84. doi:10.1042/0264-6021:3390177. PMC 1220142. PMID 10085242.
• Li DY, Zhang YC, Philips MI, et al. (1999). "Upregulation of endothelial receptor for oxidized low-density lipoprotein (LOX-1) in cultured human coronary artery endothelial cells by angiotensin II type 1 receptor activation". Circ. Res. 84 (9): 1043–9. doi:10.1161/01.res.84.9.1043. PMID 10325241.
• Kataoka H, Kume N, Miyamoto S, et al. (1999). "Expression of lectinlike oxidized low-density lipoprotein receptor-1 in human atherosclerotic lesions". Circulation. 99 (24): 3110–7. doi:10.1161/01.cir.99.24.3110. PMID 10377073.
• Li D, Saldeen T, Romeo F, Mehta JL (2000). "Oxidized LDL upregulates angiotensin II type 1 receptor expression in cultured human coronary artery endothelial cells: the potential role of transcription factor NF-kappaB". Circulation. 102 (16): 1970–6. doi:10.1161/01.cir.102.16.1970. PMID 11034947.
• Bull C, Sobanov Y, Röhrdanz B, et al. (2001). "The centromeric part of the human NK gene complex: linkage of LOX-1 and LY49L with the CD94/NKG2 region". Genes Immun. 1 (4): 280–7. doi:10.1038/sj.gene.6363678. PMID 11196705. S2CID 21961232.
• Shi X, Niimi S, Ohtani T, Machida S (2001). "Characterization of residues and sequences of the carbohydrate recognition domain required for cell surface localization and ligand binding of human lectin-like oxidized LDL receptor". J. Cell Sci. 114 (Pt 7): 1273–82. doi:10.1242/jcs.114.7.1273. PMID 11256994.
• Chen M, Narumiya S, Masaki T, Sawamura T (2001). "Conserved C-terminal residues within the lectin-like domain of LOX-1 are essential for oxidized low-density-lipoprotein binding". Biochem. J. 355 (Pt 2): 289–96. doi:10.1042/0264-6021:3550289. PMC 1221738. PMID 11284714.
• Tanimoto A, Murata Y, Nomaguchi M, et al. (2001). "Histamine increases the expression of LOX-1 via H2 receptor in human monocytic THP-1 cells". FEBS Lett. 508 (3): 345–9. doi:10.1016/S0014-5793(01)03073-3. PMID 11728449. S2CID 7257298.
• Sobanov Y, Bernreiter A, Derdak S, et al. (2002). "A novel cluster of lectin-like receptor genes expressed in monocytic, dendritic and endothelial cells maps close to the NK receptor genes in the human NK gene complex". Eur. J. Immunol. 31 (12): 3493–503. doi:10.1002/1521-4141(200112)31:12<3493::AID-IMMU3493>3.0.CO;2-9. PMID 11745369. S2CID 42415487.