UniProt functional annotation for P78380



	UniProt functional annotation for P78380

UniProt code: P78380.

Organism: Homo sapiens (Human).

Taxonomy: Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo.

Function: 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. {ECO:0000269|PubMed:11821063, ECO:0000269|PubMed:12354387, ECO:0000269|PubMed:9052782}.

Subunit: Homodimer; disulfide-linked. May form a hexamer composed of 3 homodimers. Interacts with HSP70. {ECO:0000269|PubMed:11256994, ECO:0000269|PubMed:15695803, ECO:0000269|PubMed:15939022}.

Subcellular location: Cell membrane; Lipid-anchor. Cell membrane; Single-pass type II membrane protein. Membrane raft. Secreted. Note=A secreted form also exists. Localization to membrane rafts requires palmitoylation.

Tissue specificity: Expressed at high level in endothelial cells and vascular-rich organs such as placenta, lung, liver and brain, aortic intima, bone marrow, spinal cord and substantia nigra. Also expressed at the surface of dendritic cells. Widely expressed at intermediate and low level. {ECO:0000269|PubMed:12354387, ECO:0000269|PubMed:9052782, ECO:0000269|PubMed:9828121}.

Induction: By inflammatory cytokines such as TNF, IFNG/IFN-gamma, IL6/interleukin-6 and by pathological conditions such as hyperlipidemia, hypertension and diabetes mellitus. Up-regulated in atherosclerotic lesions, by oxLDL, reactive oxygen species and fluid shear stress, suggesting that it may participate in amplification of oxLDL-induced vascular dysfunction. {ECO:0000269|PubMed:12878212, ECO:0000269|PubMed:9828121}.

Domain: The cytoplasmic region is required for subcellular sorting on the cell surface.

Domain: The C-type lectin domain mediates the recognition and binding of oxLDL.

Ptm: The intrachain disulfide-bonds prevent N-glycosylation at some sites.

Ptm: N-glycosylated.

Disease: Note=Independent association genetic studies have implicated OLR1 gene variants in myocardial infarction susceptibility.

Disease: 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. {ECO:0000269|PubMed:12384789, ECO:0000269|PubMed:12807963, ECO:0000269|PubMed:15860461}.

Annotations taken from UniProtKB at the EBI.


Organism:		Homo sapiens (Human).
Taxonomy:		Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo.



Function:		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. {ECO:0000269\|PubMed:11821063, ECO:0000269\|PubMed:12354387, ECO:0000269\|PubMed:9052782}.


Subunit:		Homodimer; disulfide-linked. May form a hexamer composed of 3 homodimers. Interacts with HSP70. {ECO:0000269\|PubMed:11256994, ECO:0000269\|PubMed:15695803, ECO:0000269\|PubMed:15939022}.
Subcellular location:		Cell membrane; Lipid-anchor. Cell membrane; Single-pass type II membrane protein. Membrane raft. Secreted. Note=A secreted form also exists. Localization to membrane rafts requires palmitoylation.
Tissue specificity:		Expressed at high level in endothelial cells and vascular-rich organs such as placenta, lung, liver and brain, aortic intima, bone marrow, spinal cord and substantia nigra. Also expressed at the surface of dendritic cells. Widely expressed at intermediate and low level. {ECO:0000269\|PubMed:12354387, ECO:0000269\|PubMed:9052782, ECO:0000269\|PubMed:9828121}.
Induction:		By inflammatory cytokines such as TNF, IFNG/IFN-gamma, IL6/interleukin-6 and by pathological conditions such as hyperlipidemia, hypertension and diabetes mellitus. Up-regulated in atherosclerotic lesions, by oxLDL, reactive oxygen species and fluid shear stress, suggesting that it may participate in amplification of oxLDL-induced vascular dysfunction. {ECO:0000269\|PubMed:12878212, ECO:0000269\|PubMed:9828121}.
Domain:		The cytoplasmic region is required for subcellular sorting on the cell surface.
Domain:		The C-type lectin domain mediates the recognition and binding of oxLDL.
Ptm:		The intrachain disulfide-bonds prevent N-glycosylation at some sites.
Ptm:		N-glycosylated.
Disease:		Note=Independent association genetic studies have implicated OLR1 gene variants in myocardial infarction susceptibility.
Disease:		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. {ECO:0000269\|PubMed:12384789, ECO:0000269\|PubMed:12807963, ECO:0000269\|PubMed:15860461}.