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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

FLASH GENE DNA RNA EXPRESSION PROTEIN DISORDER ANIMAL & CELL MODELS

DNA

TYPE	functioning gene
STRUCTURE	13.89 kb     6 Exon(s)

10 Kb 5' upstream gene genomic sequence study

MAPPING

cloned

Y

linked

N

status

provisional

Map	pter - D12S358 - OLR1 - D12S98 - cen
Text	see KLRD1

RNA

TRANSCRIPTS	type	messenger

identification nb exons type bp product Protein kDa AA specific expression Year Pubmed NM_002543 6 - 2533 NP_002534 31 273 - 1998 9828121 NM_001172632 5 - 2393 NP_001166103 - 181 - - 18191942 Loxin, lacking part of the C-terminus lectin-like domain protective against acute myocardial infarction molecular OLR1/LOXIN interaction and formation of non-functional hetero-oligomers NM_001172633 5 - 2417 NP_001166104 - 189 - - 18191942 sLOX-1 - - - - - highly overexpressed in acute aortic dissection 2013 24113299 truncated soluble form of OLR1 overepressed in acute coronary syndrome extracellular part of membrane OLR1 which is cleaved in the NECK domain

EXPRESSION

Type

widely

expressed in	(based on citations)
organ(s)	System Organ level 1 Organ level 2 Organ level 3 Organ level 4 Level Pubmed Species Stage Rna symbol Cardiovascular vessel       predominantly Homo sapiens Nervous brain diencephalon hypothalamus       brain forebrain cerebral cortex     Homo sapiens Reproductive female system placenta     highly Urinary kidney

tissue

System Tissue Tissue level 1 Tissue level 2 Level Pubmed Species Stage Rna symbol Connective bone       Epithelial sensory olfactory     Nervous central

cells

System Cell Pubmed Species Stage Rna symbol Cardiovascular endothelial cell Homo sapiens Lymphoid/Immune macrophage Nervous neuron Homo sapiens

cell lineage

cell lines

fluid/secretion

at STAGE

physiological period

pregnancy

Text	placenta, most abundant

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)

Type Gene Modification Chromosome rearrangement Protein expression Protein 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
	System Type Disorder Pubmed reproduction pregnancy   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