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FLASH GENE
Symbol OLR1 contributors: mct - updated : 14-04-2015
HGNC name oxidized low density lipoprotein (lectin-like) receptor 1
HGNC id 8133
PROTEIN
PHYSICAL PROPERTIES
STRUCTURE
motifs/domains
  • an extracellular carbohydrate recognition domain homologous with a C type lectin family, group V
  • a cytoplasmic tyrosine based inhibitory motif (ITIM)
  • a NECK domain, stabilized by the coiled-coil heptad repeat motif along the simulations
    • mono polymer homomer , dimer
    HOMOLOGY
    Homologene
    FAMILY
    CATEGORY receptor
    SUBCELLULAR LOCALIZATION extracellular
        plasma membrane
        intracellular
    intracellular,nucleus
    text type 2 membrane protein
    basic FUNCTION
  • involved in endothelial dysfunction and atherosclerosis
  • mediating calcium-dependent recognition of phosphatidylserine and apoptotic cells
  • scavenger receptor that plays a central role in the pathogenesis of atherosclerosis
  • cell surface lectin-like receptor for oxidized low density lipoproteins (ox-LDL), plays a pivotal role in host defense resulting from a broad ligand-binding spectrum
  • Ca2+-dependent phospholipid receptor, revealing novel recognition of phospholipids by mammalian lectins
  • promotes growth and migration of macrophages and induces their transformation into foam cells
  • involved in CRP-induced complement activation, and thus may serve to locate the site of CRP-induced complement activation and inflammation
  • crucial role of OLR1 and NFE2L2 in the pathogenesis of preeclampsia
  • is essential in microglia for promoting an inflammatory response in the presence of soluble neuronal-injury signals such as extracellular HSPD1, thereby linking neuroinflammation and neurotoxicity
  • may play a crucial role in the pathophysiological processes of intrahepatic cholestasis of pregnancy (ICP) caused by over-apoptosis of trophocytes
  • implicated in cytoskeletal organization and growth of cardiac fibroblasts
  • endothelial scavenger receptor that is important for oxidized low-density lipoprotein uptake
  • contributes, at least in part, to the process of fibroblast senescence and may be viewed as a new aging maker
  • association of CCL2 with OLR1 and LPA may play a role in modulating monocyte trafficking during atherogenesis
  • pivotal role as an immune modulatory protein
    • CELLULAR PROCESS
    PHYSIOLOGICAL PROCESS cardiovascular
    PATHWAY
    metabolism
    signaling
    a component
  • constituent of the NK (natural killer) complex
  • homodimer formed by an intermolecular disulfide bond
    • INTERACTION
    DNA
    RNA
    small molecule
    protein
  • molecular OLR1/LOXIN interaction and formation of non-functional hetero-oligomers
  • ROCK2 dynamically associate with OLR1 in the presence of Oxidatively modified low-density lipoprotein (OxLDL)
  • stimulates PPARG and subsequently enhances CD36 and inhibits MSR1 in macrophages
  • OLR1 through binding to extracellular HSPD1 promotes microglia-mediated neuroinflammation
  • is the main endothelial receptor for oxidized low density lipoprotein (OxLDL), and is involved in the induction of endothelial dysfunction
  • enhancement of MSR1 via inhibition of PPARG appears to be the most likely basis of sustained ox-LDL uptake in the absence or presence of OLR1
  • OLR1 binds CCL2 and the OLR1-bound CCL2 retains its ability to recruit monocytes
  • promotes migration and adhesion of bone marrow-derived mesenchymal stem cells via regulation of CCL2 expression
  • OLR1 and PCSK9 positively influence each other's expression, especially during an inflammatory reaction
  • is, at least in part, responsible for the inhibitory effect of oxidized low-density lipoprotein (ox-LDL) on macrophage migration and this process involves CAPN1 and CAPN2
  • TICAM1 regulated foam cell formation via regulation of the expression levels of CCL2, F3, OLR1
    • cell & other
    REGULATION
    Other taken up by vascular endothelium
    palmitoylated and both cysteine 36 and cysteine 46 were necessary for the recruitment of OLR1 into raft microdomains and for its ligand uptake ability
    ASSOCIATED DISORDERS
    corresponding disease(s)
    Other morbid association(s)
    TypeGene ModificationChromosome rearrangementProtein expressionProtein Function
    constitutional     --over  
    in aortic endothelial cells in diabetes
    constitutional     --over  
    in the tubulointerstitial area may be closely linked to the development and progression of diabetic nephropathy, and in particular the tubulointerstitial damage
    constitutional     --over  
    in endothelial cells of atherosclerotic lesions, but also in macrophages and smooth muscle cells
    Susceptibility
  • to acute myocardial infarction (AMI)
  • to coronary artery disease
  • to Alzheimer disease
    • Variant & Polymorphism SNP , other
  • allele APOE4 associated with 3' UTR/TT increase the risk of AD
  • SNP in the 3' UTR (C-T, 188bp from the stop codon), and 501G>C polymorphism significantly associated
    • with AMI
  • polymorphisms (intron 4/G-->A, intron 5/T-->G, and 3' UTR/T-->C) increasing the risk of coronary artery disease in white women
    • Candidate gene
    Marker
    Therapy target
    SystemTypeDisorderPubmed
    reproductionpregnancy 
    could be a potential target for therapeutic intervention in intrahepatic cholestasis during pregnancy
    ANIMAL & CELL MODELS
  • LOX-1 KO mice have low levels of the immunoglobulins in the heart (vs. the WT mice) and the expression of these immunoglobulins in the LOX-1 KO mice is upregulated several-fold when the mice are infused with Angiotensin II
  • its deletion (Lox-1 knockout, KO) reduces atherosclerosis in LDLr KO mice fed a high cholesterol diet