Search results for APOC4

Showing 11 results out of 12

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Protein (1 results from a total of 1)

Identifier: R-HSA-5215930
Species: Homo sapiens
Compartment: extracellular region
Primary external reference: UniProt: APOC4: P55056

DNA Sequence (1 results from a total of 1)

Identifier: R-HSA-9035181
Species: Homo sapiens
Compartment: nucleoplasm
Primary external reference: ENSEMBL: ENSEMBL:ENSG00000267467

Reaction (7 results from a total of 8)

Identifier: R-HSA-9035143
Species: Homo sapiens
Compartment: nucleoplasm
Apolipoprotein C4 (APOC4) is present in the APOE, APOC1, APOC4 and APOC2-gene cluster which is induced by natural and synthetic ligands of liver X receptors (LXRα, NR1H3 and LXRβ, NR1H2) in both human and mouse macrophages (Mak PA et al. 2002). The induction of all four mRNAs was greatly attenuated in macrophages derived from LXR α/β-/- mice (Mak PA et al. 2002). Cell reporter assays suggest that the LXR response elements (LXRE) in the multienhancer regions ME.1 and ME.2, which confer tissue-specific expression in macrophages and adipocytes (Shih SJ et al. 2000), are necessary for the expression of this gene cluster (Mak PA et al. 2002). These secreted apolipoproteins regulate lipid transport and catabolism.
Identifier: R-HSA-8866321
Species: Homo sapiens
Compartment: extracellular region
Newly formed very low-density lipoprotein (VLDL) released from the liver can acquire lipoproteins in the circulation. Apolipoprotein C-I (APOC1) is a 6.6 kDa apolipoprotein that is synthesised mainly in the liver but also in other tissues. It is a constituent of triglyceride-rich lipoproteins (around 10% of the protein of VLDLs and 2% of HDLs) that slow the circulatory clearance of triglyceride-rich lipoproteins by a variety of mechanisms. As well as binding and inhibiting triglyceride-rich lipoprotein uptake by the very low-density lipoprotein receptor (VLDLR), it can also binds free fatty acids (FAs) in the circulation, reducing their uptake by cells (Shachter 2001, Hansen et al. 2011). A minor constituent of VLDL is apolipoprotein IV (APO4) (Kotite et al. 2003).
Identifier: R-HSA-9035279
Species: Homo sapiens
Compartment: nucleoplasm
The APOC4 gene is transcribed to yield mRNA and the mRNA is translated to yield protein.

Ligand-activated liver X receptors (LXRα, NR1H3 and LXRβ NR1H2) induce expression of a cluster of apolipoprotein genes APOE, APOC1, APOC2 and APOC4 in both human and mouse macrophages (Mak PA et al. 2002). The induction of all four mRNAs was greatly attenuated in peritoneal macrophages derived from LXR α/β-/- mice (Mak PA et al. 2002). Cel reporter assays suggest that the LXR response elements (LXRE) in the multienhancer regions ME.1 and ME.2, which confer tissue-specific expression in macrophages and adipocytes (Shih SJ et al. 2000), are necessary for the expression of this gene cluster (Mak PA et al. 2002). These secreted apolipoproteins regulate lipid transport and catabolism.

Identifier: R-HSA-8854462
Species: Homo sapiens
Compartment: extracellular region, plasma membrane
Very low-density lipoproteins (VLDLs) are produced in the liver to transport endogenous triglycerides, phospholipids, cholesterol, and cholesteryl esters in the hydrophilic environment of the bloodstream. They comprise triglycerides (50-60%), cholesterol (10-12%), cholesterol esters (4-6%), phospholipids (18-20%), and apolipoprotein B (8-12%). Of the protein content, two other apolipoproteins are constituents; apolipoprotein C-I (APOC around 20%) (Westerterp et al. 2007) and apolipoprotein C4 (APOC4, minor amount) (Kotite et al. 2003). After release from the liver, circulating VLDL particles can bind very low-density lipoprotein receptors (VLDLR) (Sakai et al. 1994) on extra-hepatic target cells and undergo endocytosis (Go & Mani 2012). VLDL uptake by VLDLR represents a minor contribution towards VLDL metabolism. The majority of VLDL is catalysed by lipoprotein lipase (LPL) which hydrolyses TAGs from VLDL, converting it to intermediate-density lipoprotein (IDL). IDL can be further hydrolysed by hepatic lipase to cholesterol-rich low-density lipoprotein (LDL).

VLDLR consists of five functional domains that resemble the LDL receptor. It is highly expressed in tissues that actively metabolise fatty acids as a source of energy. Binding of VLDLs to VLDLR appears to be inhibited by apolipoprotein C-I (APOC1), therby slowing the clearance of triglyceride-rich lipoproteins from the circulation (Westerterp et al. 2007). The APOE/C1/C4/C2 gene cluster is closely associated with plasma lipid levels, atherosclerotic plaque formation, and thereby implicated in the development of coronary artery disease and Alzheimer’s disease (Xu et al. 2015).
Identifier: R-HSA-9031510
Species: Homo sapiens
Compartment: nucleoplasm
The APOC1 gene is transcribed to yield mRNA and the mRNA is translated to yield protein.

Ligand-activated liver X receptors (LXRα, NR1H3 and LXRβ NR1H2) induce expression of a cluster of apolipoprotein genes APOE, APOC1, APOC2 and APOC4 in both human and mouse macrophages (Mak PA et al. 2002). Induction of APOC2 mRNA was attenuated or abolished in macrophages derived from LXR α/β-/- mice (Mak PA et al. 2002).

Identifier: R-HSA-9031518
Species: Homo sapiens
Compartment: nucleoplasm
Ligand-activated liver X receptors (LXRα, NR1H3 and LXRβ NR1H2) induce expression of a cluster of apolipoprotein genes APOE, APOC1, APOC2 and APOC4 in both human and mouse macrophages (Mak PA et al. 2002). Induction was attenuated or abolished in macrophages derived from LXR α/β-/- mice. Studies with reporter genes suggest that the LXR response element (LXRE) in the distal multienhancer regions ME.1 and ME.2 are necessary for the expression of this gene cluster (Mak PA et al. 2002). These secreted apolipoproteins regulate lipid transport and catabolism. In particular, APOC1 has been suggested to serve as an inhibitor of cholesteryl ester transfer protein (CETP) activity to impact cholesterol distribution among lipoprotein particles (Gautier T et al. 2000).
Identifier: R-HSA-9031527
Species: Homo sapiens
Compartment: nucleoplasm
The APOC2 gene is transcribed to yield mRNA and the mRNA is translated to yield protein.

Ligand-activated liver X receptors (LXRα, NR1H3 and LXRβ NR1H2) induce expression of a cluster of apolipoprotein genes APOE, APOC1, APOC2 and APOC4 in both human and mouse macrophages (Mak PA et al. 2002). The induction of all four mRNAs was greatly attenuated in peritoneal macrophages derived from LXR α/β-/- mice (Mak PA et al. 2002). Cel reporter assays suggest that the LXR response elements (LXRE) in the multienhancer regions ME.1 and ME.2, which confer tissue-specific expression in macrophages and adipocytes (Shih SJ et al. 2000), are necessary for the expression of this gene cluster (Mak PA et al. 2002). These secreted apolipoproteins regulate lipid transport and catabolism.

Pathway (2 results from a total of 2)

Identifier: R-HSA-8866423
Species: Homo sapiens
Very low-density lipoprotein (VLDL) is synthesised in the liver in two steps. First, apolipoprotein B-100 (APOB-100) is co- and post-translationally lipidated in the rough ER lumen. After transfer to the smooth ER lumen, lipidated APOB-100 acquires lipids to become bona fide VLDL. Lipid composition of VLDL - triglycerides (50-60%), cholesterol (10-12%), cholesterol esters (4-6%), phospholipids (18-20%), and apolipoprotein B (8-12%). When VLDL assembly is complete, it travels along the Golgi apparatus to be eventually secreted from the liver into general circulation. In circulation, VLDL can acquire more lipoproteins. At least two other apolipoproteins are constituents; apolipoprotein C-I (APOC1, around 20%) and apolipoprotein C4 (APOC4, minor amount) (Gibbons et al. 2004; Olofsson et al. 2000).
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).
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