Search results for ABCA1

Showing 18 results out of 83

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Types

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Protein (3 results from a total of 21)

Identifier: R-HSA-194209
Species: Homo sapiens
Compartment: plasma membrane
Primary external reference: UniProt: O95477
Identifier: R-HSA-5682105
Species: Homo sapiens
Compartment: endoplasmic reticulum membrane
Primary external reference: UniProt: O95477
Identifier: R-HSA-5682199
Species: Homo sapiens
Compartment: plasma membrane
Primary external reference: UniProt: ABCA1: O95477

RNA Sequence (1 results from a total of 1)

Identifier: R-HSA-9618483
Species: Homo sapiens
Compartment: cytosol
Primary external reference: ENSEMBL: ABCA1 mRNA: ENST00000374736.7

DNA Sequence (1 results from a total of 1)

Identifier: R-HSA-5649950
Species: Homo sapiens
Compartment: nucleoplasm
Primary external reference: ENSEMBL: ENSG00000165029

Reaction (3 results from a total of 37)

Identifier: R-HSA-1989765
Species: Homo sapiens
Compartment: nucleoplasm, plasma membrane
The ATP-binding cassette transporter A1 (ABCA1) gene is transcribed to yield mRNA and the mRNA is translated to yield protein.
Identifier: R-HSA-9619756
Species: Homo sapiens
Compartment: cytosol, plasma membrane
In addition to its well defined role as a transcription factor, liver X receptor β (LXRβ or NR1H2) can directly bind to the C-terminal region of ATP-binding cassette A1 (ABCA1) in the human macrophage-like (THP-1) and human embryonic kidney 293 (HEK293) cell lines to impact ABCA1 protein function (Hozoji M et al. 2008; Hozoji-Inada M et al. 2011). In the absence of cholesterol accumulation in THP-1 cells, the ABCA1:NR1H2 complex stably localizes to the plasma membrane, but apolipoprotein A-I (apoA-I) binding or cholesterol efflux does not occur (Hozoji M et al. 2008; Hozoji-Inada M et al. 2011). Exogenously added NR1H2 ligands, which mimic cholesterol accumulation, cause NR1H2 (LXRβ) to dissociate from ABCA1, thus freeing ABCA1 for apoA-I binding and subsequent cholesterol efflux (Hozoji M et al. 2008; Hozoji-Inada M et al. 2011). Photoaffinity labeling experiments with 8-azido-[α-(32)P]ATP suggested that the interaction of NR1H2 (LXRβ) with ABCA1 inhibits ATP binding by ABCA1 (Hozoji-Inada M et al. 2011).
Identifier: R-HSA-9618479
Species: Homo sapiens
Compartment: cytosol, plasma membrane
The ATP-binding cassette sub-family A member 1 (ABCA1) mRNA is translated to yield ABCA1 protein.

Synthetic agonists of liver X-receptors (LXRα, NR1H3 and LXRβ, NR1H2) or cholesterol-loading significantly induced the expression of ABCA1 protein in mouse RAW 264.7 and human THP-1 macrophage cell lines (Beyea MM et al. 2007; Ku CS et al. 2012). Similar regulation of ABCA1 protein expression by NR1H2, 3 agonists was observed in human peripheral blood-derived monocytes (Mauerer R et al. 2009). Treatment of THP-1 macrophages with endogenous (25-hydroxycholesterol) or synthetic (T0901317) ligands of NR1H2,3 stimulated both transcriptional and posttranscriptional pathways to enhance ABCA1 expression (Ignatova ID et al. 2013). Further, partial inhibition of oxidosqualene:lanosterol cyclase (OSC) stimulated synthesis of the NR1H2,3 agonist 24(S),25-epoxycholesterol (24(S),25-epoxy) and enhanced ABCA1-mediated cholesterol efflux in THP-1 cells (Beyea MM et al. 2007). NR1H3 and NR1H2-induced expression of ABCA1 is thought to promote cellular cholesterol transfer to lipid-poor apolipoproteins such as ApoA1 and ApoE in the formation of nascent HDL particles (Ignatova ID et al. 2013; Vedhachalam C et al. 2007). Loss of ABCA1 in humans results in Tangier disease, a condition in which patients have extremely low levels of circulating HDL, massive accumulation of cholesterol in macrophages, and an increased risk for developing atherosclerosis (Rust S et al. 1999).

MicroRNAs miR-26 and miR-33 negatively regulate the translation of ABCA1 mRNA and thus repress the NR1H2, NR1H3-dependent cholesterol efflux from macrophages (Sun D et al. 2012; Rayner KJ et al. 2010). MicroRNA miR-144 also binds the ABCA1 3’UTR to prohibit translation and reduce ABCA1-mediated cholesterol efflux from hepatocytes (de Aguiar Vallim TQ et al. 2013)

Set (2 results from a total of 2)

Identifier: R-HSA-5682194
Species: Homo sapiens
Compartment: plasma membrane
Identifier: R-HSA-5682322
Species: Homo sapiens
Compartment: plasma membrane

Complex (3 results from a total of 14)

Identifier: R-HSA-216753
Species: Homo sapiens
Compartment: plasma membrane
Identifier: R-HSA-5682087
Species: Homo sapiens
Compartment: endoplasmic reticulum membrane
Identifier: R-HSA-9624931
Species: Homo sapiens
Compartment: cytosol

Pathway (3 results from a total of 5)

Identifier: R-HSA-5682113
Species: Homo sapiens
In an ATP-dependent reaction, ATP-binding cassette sub-family A member 1 (ABCA1) mediates the movement of intracellular cholesterol to the extracellular face of the plasma membrane. Cholesterol associated with cytosolic vesicles is a substrate for this reaction. Under physiologocal conditions, the active form of ABCA1 is post-translationally modified (palmitoylated and phosphorylated), predominantly a tetramer and is associated with apolipoprotein A-I (APOA1). Defects in ABCA1 can cause Tangier disease (TGD; MIM:205400 aka high density lipoprotein deficiency type 1), an autosomal recessive disorder characterised by significantly reduced levels of plasma high density lipoproteins (HDL) resulting in tissue accumulation of cholesterol esters (Brooks-Wilson et al. 1999). Low HDL levels are among the most common biochemical abnormalities observed in coronary heart disease (CHD) patients (Kolovou et al. 2006, Iatan et al. 2008, Iatan et al. 2012).
Identifier: R-HSA-5682294
Species: Homo sapiens
ATP-binding cassette sub-family A member 12 (ABCA12) is thought to function as an epidermal keratinocyte lipid transporter. These lipids form extracellular lipid layers in the stratum corneum of the epidermis, essential for skin barrier function. Defects in ABCA12 results in the loss of the skin lipid barrier, leading to autosomal recessive congenital ichthyosis 4B (ARCI4B; MIM:242500, aka harlequin ichthyosis, HI). ARCI4B shows the most severe phenotype of the congenital ichthyoses, with newborns having a thick covering of armour-like scales. The skin dries out to form hard diamond-shaped plaques separated by fissures. Affected babies are often born prematurely and rarely survive the perinatal period (Akiyama et al. 2005, Akiyama 2010, 2014).
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).

Icon (2 results from a total of 2)

Species: Homo sapiens
Curator: Bijay Jassal
Designer: Cristoffer Sevilla
ABCA1 icon
Phospholipid-transporting ATPase ABCA1
Species: Homo sapiens
Curator: Bijay Jassal
Designer: Cristoffer Sevilla
ABCA12 icon
ATP-binding cassette sub-family A member 12
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