Search results for APOE

Showing 18 results out of 50

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Species

Types

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Reaction types

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Protein (5 results from a total of 10)

Identifier: R-HSA-2429687
Species: Homo sapiens
Compartment: early endosome
Primary external reference: UniProt: APOE: P02649
Identifier: R-HSA-6784908
Species: Homo sapiens
Compartment: endoplasmic reticulum lumen
Primary external reference: UniProt: APOE: P02649
Identifier: R-HSA-174646
Species: Homo sapiens
Compartment: extracellular region
Primary external reference: UniProt: APOE: P02649
Identifier: R-HSA-3221641
Species: Homo sapiens
Compartment: endocytic vesicle lumen
Primary external reference: UniProt: APOE: P02649
Identifier: R-HSA-174615
Species: Homo sapiens
Compartment: plasma membrane
Primary external reference: UniProt: P02649

Interactor (2 results from a total of 2)

Identifier: P02649-PRO_0000001987
Species: Homo sapiens
Primary external reference: UniProt: P02649-PRO_0000001987
Identifier: EBI-21404505
Species: Homo sapiens
Primary external reference: IntAct: EBI-21404505

DNA Sequence (1 results from a total of 1)

Identifier: R-HSA-8869591
Species: Homo sapiens
Compartment: nucleoplasm
Primary external reference: ENSEMBL: ENSG00000130203

Reaction (5 results from a total of 32)

Identifier: R-HSA-9031522
Species: Homo sapiens
Compartment: nucleoplasm
Apolipoprotein E (APOE), a 34-kD glycoprotein, is involved in lipoprotein clearance by serving as a ligand for the low-density lipoprotein (LDL) receptor family. APOE is primarily lipidated via the ATP-binding cassette transporter A1 (ABCA1), and both are under transcriptional regulation by the liver X receptor α (LXRα or NR1H3) and LXRβ (NR1H2) (Laffitte BA et al. 2001; Beyea MM et al. 2007). The ligand-activated NR1H2 and NR1H3, whose natural ligands are oxysterols, function as obligate heterodimers with retinoid X receptor (RXR) to regulate the expression of target genes through binding to LXR response elements (LXREs) within the regulatory region of their target genes. Both NR1H2:RXRα and NR1H3 :RXRα heterodimers were reported to regulate APOE transcription directly through interaction with conserved LXREs found within tissue-specific enhancer regions (multienhancers ME.1 and ME.2) that confer APOE expression in adipose tissue and macrophages (Shih SJ et al. 2000; Laffitte BA et al. 2001). A low-affinity LXRE was also found in the promoter region of the APOE gene (Laffitte BA et al. 2001). Further, oxysterol-binding protein related protein 1S (ORP1S) was shown to associate with NR1H2 and NR1H3 in the nucleus (Lee S et al. 2012). ORP1S promoted the binding of the receptors to LXREs and specifically enhanced NR1H2,3-dependent transcription of APOE via the ME.1 and ME.2 of the APOE gene (Lee S et al. 2012).
Identifier: R-HSA-2423785
Species: Homo sapiens
Compartment: extracellular region, plasma membrane
When the low-density lipoprotein receptor (LDLR) is missing, saturated or inhibited, chylomicron remnants (CRs) containing all-trans-retinyl esters (atREs) bind apolioprotein E (apoE). ApoE, secreted by hepatocytes, acts as a high-affinity ligand for the LDL-related receptor protein (LRP) family. CR:atREs:apoE then binds to cell-surface heparan sulfate proteoglycan (HSPG), abundant in the space of Disse. HSPG/apoE binding plays a critical role in the capture of CR:atREs, ready for internalization via LRPs (Futamura et al. 2005, Yamauchi et al. 2008).
Identifier: R-HSA-9612246
Species: Homo sapiens
Compartment: nucleoplasm
The intracellular fragment of ERBB4, ERBB4s80 (E4ICD) binds to the promoter region of the APOE gene, about 2 kb upstream from the transcription start site. The ERBB4s80 binding site overlaps with HNF4 and ETS1 binding sites (Wali et al. 2014).
Identifier: R-HSA-9031512
Species: Homo sapiens
Compartment: nucleoplasm
The apolipoprotein E (APOE) gene is transcribed to yield mRNA and the mRNA is translated to yield protein. APOE, a 34-kD glycoprotein, is involved in lipoprotein clearance by serving as a ligand for the low-density lipoprotein (LDL) receptor family. APOE is primarily lipidated via the ATP-binding cassette transporter 1 (ABCA1), and both are under transcriptional regulation by the liver X receptor α (LXRα or NR1H3) and LXRβ (NR1H2) whose natural ligands are oxysterols such as 24(S),25-epoxycholesterol (24(S),25-epoxy) (Laffitte BA et al. 2001; Beyea MM et al. 2007). The endogenous and synthetic agonists of NR1H2 or NR1H3 increased expression of APOE in human and murine macrophages, and murine adipocytes but not in liver (Laffitte BA et al. 2001; Mak PA et al 2002; Beyea MM et al. 2006). This tissue-specific regulation is conferred by the presence of LXR response elements (LXREs) in multienhancer regions ME.1 and ME.2 downstream of the APOE gene that are revealed only in adipose tissue and macrophages (Shih SJ et al. 2000). In addition, ligand-activated NR1H2 and NR1H3 lead to a dramatic increase in APOE mRNA and protein expression as well as secretion of APOE in a human astrocytoma cell line (CCF-STTG1 cells) to impact cholesterol efflux (Liang Y et al. 2004; Abildayeva K et al. 2006). In the central nervous system, APOE is considered a major apoprotein acceptor for the efflux of cholesterol in the formation of high-density lipoprotein (HDL)-like particles necessary for intercellular lipid trafficking, and is implicated in various neurodegenerative diseases, such as Alzheimer’s (reviewed in Hirsch-Reinshagen V & Wellington CL 2007).
Identifier: R-HSA-9612243
Species: Homo sapiens
Compartment: nucleoplasm, extracellular region
Transcription of the APOE gene, encoding Apolipoprotein E, involved in binding and internalization of lipoprotein particles, is stimulated by the intracellular fragment of ERBB4, ERBB4s80 (E4ICD) (Wali et al. 2014).

Complex (1 results from a total of 1)

Identifier: R-HSA-9612240
Species: Homo sapiens
Compartment: nucleoplasm

Pathway (4 results from a total of 4)

Identifier: R-HSA-9629232
Species: Homo sapiens
NEIL3 is a DNA N-glycosylase involved in base excision repair (BER), the primary repair pathway for oxidative DNA damage. NEIL3 can detect and remove oxidized guanine, in the form of 5-guanidinohydatoin and spiroiminodihydantoin, and oxidized thymine, in the form of thymine glycol. NEIL3 has a preference for single strand DNA (ssDNA) and is implicated in repair of oxidative DNA damage at telomeres (Zhou et al. 2013). A NEIL3 disease variant NEIL3 D132 is unable to cleave 5 guanidinohydantoin (Gh) from oxidatively damaged DNA. Individuals harboring a NEIL3 D132V homozygous mutation are predisposed to development of autoimmune diseases (Massaad et al. 2016) and NEIL3 depletion is also associated with an increase in telomere damage and loss (Zhou et al. 2017). NEIL3 unhooks DNA interstrand cross-links (ICLs) during DNA replication. NEIL3 resolves psoralen- and abasic site-induced ICLs in a Fanconi anemia (FA) pathway-independent manner (Semlow et al. 2016, Martin et al. 2017).
A polymorphism in one of the NEIL3 gene splice sites may increase the risk of myocardial infarction (Skarpengland et al. 2015). NEIL3 expression in the heart increases after heart failure in humans and after myocardial infarction in mouse disease models. Neil3 knockout mice show increased mortality after myocardial infarction, but there is no increase in the amount of DNA damage in Neil3 knockout hearts. In the heart, NEIL3 may function in the epigenetic regulation of gene expression and facilitate transcriptional response to myocardial infarction (Olsen et al. 2017). NEIL3 mRNA expression is increased in human carotid plaques and Neil3 deficiency accelerates plaque formation in Apoe knockout mice, but it appears that this is not correlated with oxidative DNA damage (Skarpengland et al. 2016).
The function of NEIL3 in removal of hydantoins from single strand DNA may be important for removal of replication blocks in proliferating cells. Mouse embryonic fibroblasts and neuronal stem cell derived from Neil3 knockout mouse embryos show decreased proliferation capacity and increased sensitivity to DNA damaging agents (Rolseth et al. 2013). NEIL3 may be required for maintenance of adult neurogenesis, as Neil3 knockout mice exhibit learning and memory deficits and synaptic irregularities in the hippocampus (Regnell et al. 2012). In addition, NEIL3 deficient neuronal stem cells exhibits signs of premature senescence (Reis and Hermanson 2012) and Neil3 knockout mice show reduced ability to augment neurogenesis to repair damage induced hypoxia ischemia (Sejersted et al. 2011).
Mice that are triple knockout for Neil1, Neil2 and Neil3 do not show a predisposition to tumour formation or changes in telomere length (Rolseth et al. 2017).
Identifier: R-HSA-432142
Species: Homo sapiens
Compartment: plasma membrane
Physiological concentrations (1g/L) of Low density lipoprotein (LDL) enhance platelet aggregation responses initiated by thrombin, collagen, and ADP. This enhancement involves the rapid phosphorylation of p38 mitogen-activated protein kinase (p38MAPK) at Thr180 and Tyr182. The receptor for LDL is ApoER2, a splice variant of the classical ApoE receptor. ApoER2 stimulation leads to association of the Src family kinase Fgr which is probably responsible for subsequent phosphorylation of p38MAPK. This stimulation is transient because LDL also increases the activity of PECAM-1, which stimulates phosphatases that dephosphorylate p38MAPK.
Identifier: R-HSA-9029569
Species: Homo sapiens
Compartment: nucleoplasm
The liver X receptors (LXRs), LXRα (NR1H3) and LXRβ (NR1H2), are nuclear receptors that are activated by endogenous oxysterols, oxidized derivatives of cholesterol (Janowski BA et al. 1996). When cellular oxysterols accumulate as a result of increasing concentrations of cholesterol, NR1H2,3 induce the transcription of genes that protect cells from cholesterol overload (Zhao C & Dahlman‑Wright K 2010; Ma Z et al. 2017). In peripheral cells such as macrophages, NR1H2 and NR1H3 increase cholesterol efflux by inducing expression of ATP-binding cassette subfamily A type 1 (ABCA1), ABCG1, and apolipoprotein APOE (Jakobsson T et al. 2009; Laffitte BA et al. 2001; Mak PA et al. 2002). In the intestine, LXR agonists decrease cholesterol absorption through induction of ABCA1, ABCG5, and ABCG8 (Repa JJ et al. 2000; Back SS et al. 2013). Cholesterol removal from non-hepatic peripheral cells, such as lipid-laden macrophages, and its delivery back to the liver for catabolism and excretion are processes collectively known as reverse cholesterol transport (RCT) (Francis GA 2010; Rosenson RS et al. 2012). This Reactome module describes the activation of several direct NR1H2,3 target genes that are closely associated with the RCT pathway, including genes encoding membrane lipid transporters, such ABCA1, ABCG1, ABCG5, ABCG8 and a cluster of apolipoprotein genes APOE, APOC1, APOC2 and APOC4 (Jakobsson T et al. 2009; Back SS et al. 2013; Mak PA et al. 2002).
Identifier: R-HSA-8964058
Species: Homo sapiens
HDL (high-density lipoprotein) particles play a central role in the reverse transport of cholesterol, the process by which cholesterol in tissues other than the liver is returned to the liver for conversion to bile salts and excretion from the body and provided to tissues such as the adrenals and gonads for steroid hormone synthesis (Tall et al. 2008).
ABCG1 mediates the movement of intracellular cholesterol to the extracellular face of the plasma membrane where it is accessible to circulating HDL (Vaughan & Oram 2005). Spherical (mature) HDL particles can acquire additional molecules of free cholesterol (CHOL) and phospholipid (PL) from cell membranes.
At the HDL surface, LCAT (lecithin-cholesterol acyltransferase) associates strongly with HDL particles and, activated by apoA-I, catalyzes the reaction of cholesterol and phosphatidylcholine to yield cholesterol esterified with a long-chain fatty acid and 2-lysophosphatidylcholine. The hydrophobic cholesterol ester reaction product is strongly associated with the HDL particle while the 2-lysophosphatidylcholine product is released. Torcetrapib associates with a molecule of CETP and a spherical HDL particle to form a stable complex, thus trapping CETP and inhibiting CETP-mediated lipid transfer between HDL and LDL (Clark et al. 2006).
Spherical HDL particles can bind apoC-II, apoC-III and and apoE proteins.
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