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)
End	10,172,138 bp
Gene location (Mouse)
Chr.	Chromosome 6 (mouse)
End	129,484,128 bp
RNA expression pattern
	Top expressed in
	right lung; ; C1 segment; ; bone marrow cell; ; 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
	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
	4973
	108078
	ENSG00000173391
	ENSMUSG00000030162
	P78380
	Q9EQ09
	NM_001172632; NM_001172633; NM_002543
	NM_001301094; NM_001301096; NM_138648
	NP_001166103; NP_001166104; NP_002534
	NP_001288023; NP_001288025; NP_619589
	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

LOX-1 is the main receptor for oxidized LDL on endothelial cells, macrophages, smooth muscle cells,⁶ and other cell types.⁷ But minimally oxidized LDL is more readily recognized by the TLR4 receptor, and highly oxidized LDL is more readily recognized by the CD36 receptor.⁸

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.

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.⁷⁹

LOX-1 may be involved in the regulation of Fas-induced apoptosis. Oxidized LDL induces endothelial cell apoptosis through LOX-1 binding.⁶ Other ligands for LOX-1 include oxidized high-density lipoprotein, advanced glycation end-products, platelets, and apoptotic cells.⁶⁹ The binding of platelets to LOX-1 causes a release of vasoconstrictive endothelin, which induces endothelial dysfunction.⁹

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).⁷ Macrophage affinity for unmodified LDL particles is low, but is greatly increased when the LDL particles are oxidized.¹⁰ LDL oxidation occurs in the sub-endothelial space, rather than in the circulation.¹⁰ But oxidized cholesterol from foods cooked at high temperature can also be a source of oxysterols.⁸

OLR1 gene polymorphisms have been associated with coronary artery disease.¹¹

References

GRCh38: Ensembl release 89: ENSG00000173391 – Ensembl, May 2017
GRCm38: Ensembl release 89: ENSMUSG00000030162 – 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.
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.
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.
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.
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.
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.
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.
Salehipour P, Rezagholizadeh F, Mahdiannasser M, Kazerani R, Modarressi MH (2021). "Association of OLR1 gene polymorphisms with the risk of coronary artery disease: A systematic review and meta-analysis". Heart Lung. 50 (2): 334–343. doi:10.1016/j.hrtlng.2021.01.015. PMID 33524863.

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.

[refGRCh38Ensembl-1] GRCh38: Ensembl release 89: ENSG00000173391 – Ensembl, May 2017

[refGRCm38Ensembl-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.

[pmid9763655-5] 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.

[pmid23935243-6] 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.

[pmid23124189-7] 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.

[pmid28969682-8] 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.

[pmid10618423-9] 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.

[pmid28936395-10] 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.

[11] Salehipour P, Rezagholizadeh F, Mahdiannasser M, Kazerani R, Modarressi MH (2021). "Association of OLR1 gene polymorphisms with the risk of coronary artery disease: A systematic review and meta-analysis". Heart Lung. 50 (2): 334–343. doi:10.1016/j.hrtlng.2021.01.015. PMID 33524863.

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