1yxj

Structural highlights

Disease

[OLR1_HUMAN] Note=Independent association genetic studies have implicated OLR1 gene variants in myocardial infarction susceptibility.^{[1] [2] [3] [4] [5]} Note=OLR1 may be involved in Alzheimer disease (AD). Involvement in AD is however unclear: according to some authors (PubMed:12354387, PubMed:12810610 and PubMed:15976314), variations in OLR1 modify the risk of AD, while according to other (PubMed:15000751 and PubMed:15060104) they do not.^{[6] [7] [8] [9] [10]}

Function

[OLR1_HUMAN] Receptor that mediates the recognition, internalization and degradation of oxidatively modified low density lipoprotein (oxLDL) by vascular endothelial cells. OxLDL is a marker of atherosclerosis that induces vascular endothelial cell activation and dysfunction, resulting in pro-inflammatory responses, pro-oxidative conditions and apoptosis. Its association with oxLDL induces the activation of NF-kappa-B through an increased production of intracellular reactive oxygen and a variety of pro-atherogenic cellular responses including a reduction of nitric oxide (NO) release, monocyte adhesion and apoptosis. In addition to binding oxLDL, it acts as a receptor for the HSP70 protein involved in antigen cross-presentation to naive T-cells in dendritic cells, thereby participating in cell-mediated antigen cross-presentation. Also involved in inflammatory process, by acting as a leukocyte-adhesion molecule at the vascular interface in endotoxin-induced inflammation. Also acts as a receptor for advanced glycation end (AGE) products, activated platelets, monocytes, apoptotic cells and both Gram-negative and Gram-positive bacteria.^{[11] [12] [13]}

Evolutionary Conservation

Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf.

References

1. ↑ Luedecking-Zimmer E, DeKosky ST, Chen Q, Barmada MM, Kamboh MI. Investigation of oxidized LDL-receptor 1 (OLR1) as the candidate gene for Alzheimer's disease on chromosome 12. Hum Genet. 2002 Oct;111(4-5):443-51. Epub 2002 Aug 16. PMID:12384789 doi:10.1007/s00439-002-0802-7
2. ↑ Lambert JC, Luedecking-Zimmer E, Merrot S, Hayes A, Thaker U, Desai P, Houzet A, Hermant X, Cottel D, Pritchard A, Iwatsubo T, Pasquier F, Frigard B, Conneally PM, Chartier-Harlin MC, DeKosky ST, Lendon C, Mann D, Kamboh MI, Amouyel P. Association of 3'-UTR polymorphisms of the oxidised LDL receptor 1 (OLR1) gene with Alzheimer's disease. J Med Genet. 2003 Jun;40(6):424-30. PMID:12807963
3. ↑ Bertram L, Parkinson M, Mullin K, Menon R, Blacker D, Tanzi RE. No association between a previously reported OLR1 3' UTR polymorphism and Alzheimer's disease in a large family sample. J Med Genet. 2004 Apr;41(4):286-8. PMID:15060104
4. ↑ Pritchard A, St Clair D, Lemmon H, Mann DM, Lendon C. No association between polymorphisms in the lectin-like oxidised low density lipoprotein receptor (ORL1) gene on chromosome 12 and Alzheimer's disease in a UK cohort. Neurosci Lett. 2004 Aug 12;366(2):126-9. PMID:15276231 doi:10.1016/j.neulet.2004.05.023
5. ↑ D'Introno A, Solfrizzi V, Colacicco AM, Capurso C, Torres F, Capurso SA, Capurso A, Panza F. Polymorphisms in the oxidized low-density lipoprotein receptor-1 gene and risk of Alzheimer's disease. J Gerontol A Biol Sci Med Sci. 2005 Mar;60(3):280-4. PMID:15860461
6. ↑ Luedecking-Zimmer E, DeKosky ST, Chen Q, Barmada MM, Kamboh MI. Investigation of oxidized LDL-receptor 1 (OLR1) as the candidate gene for Alzheimer's disease on chromosome 12. Hum Genet. 2002 Oct;111(4-5):443-51. Epub 2002 Aug 16. PMID:12384789 doi:10.1007/s00439-002-0802-7
7. ↑ Lambert JC, Luedecking-Zimmer E, Merrot S, Hayes A, Thaker U, Desai P, Houzet A, Hermant X, Cottel D, Pritchard A, Iwatsubo T, Pasquier F, Frigard B, Conneally PM, Chartier-Harlin MC, DeKosky ST, Lendon C, Mann D, Kamboh MI, Amouyel P. Association of 3'-UTR polymorphisms of the oxidised LDL receptor 1 (OLR1) gene with Alzheimer's disease. J Med Genet. 2003 Jun;40(6):424-30. PMID:12807963
8. ↑ Bertram L, Parkinson M, Mullin K, Menon R, Blacker D, Tanzi RE. No association between a previously reported OLR1 3' UTR polymorphism and Alzheimer's disease in a large family sample. J Med Genet. 2004 Apr;41(4):286-8. PMID:15060104
9. ↑ Pritchard A, St Clair D, Lemmon H, Mann DM, Lendon C. No association between polymorphisms in the lectin-like oxidised low density lipoprotein receptor (ORL1) gene on chromosome 12 and Alzheimer's disease in a UK cohort. Neurosci Lett. 2004 Aug 12;366(2):126-9. PMID:15276231 doi:10.1016/j.neulet.2004.05.023
10. ↑ D'Introno A, Solfrizzi V, Colacicco AM, Capurso C, Torres F, Capurso SA, Capurso A, Panza F. Polymorphisms in the oxidized low-density lipoprotein receptor-1 gene and risk of Alzheimer's disease. J Gerontol A Biol Sci Med Sci. 2005 Mar;60(3):280-4. PMID:15860461
11. ↑ Sawamura T, Kume N, Aoyama T, Moriwaki H, Hoshikawa H, Aiba Y, Tanaka T, Miwa S, Katsura Y, Kita T, Masaki T. An endothelial receptor for oxidized low-density lipoprotein. Nature. 1997 Mar 6;386(6620):73-7. PMID:9052782 doi:10.1038/386073a0
12. ↑ Hayashida K, Kume N, Minami M, Kita T. Lectin-like oxidized LDL receptor-1 (LOX-1) supports adhesion of mononuclear leukocytes and a monocyte-like cell line THP-1 cells under static and flow conditions. FEBS Lett. 2002 Jan 30;511(1-3):133-8. PMID:11821063
13. ↑ Delneste Y, Magistrelli G, Gauchat J, Haeuw J, Aubry J, Nakamura K, Kawakami-Honda N, Goetsch L, Sawamura T, Bonnefoy J, Jeannin P. Involvement of LOX-1 in dendritic cell-mediated antigen cross-presentation. Immunity. 2002 Sep;17(3):353-62. PMID:12354387
14. ↑ Ohki I, Ishigaki T, Oyama T, Matsunaga S, Xie Q, Ohnishi-Kameyama M, Murata T, Tsuchiya D, Machida S, Morikawa K, Tate S. Crystal structure of human lectin-like, oxidized low-density lipoprotein receptor 1 ligand binding domain and its ligand recognition mode to OxLDL. Structure. 2005 Jun;13(6):905-17. PMID:15939022 doi:10.1016/j.str.2005.03.016