Phospholipid-transporting ATPase ABCA1
Also known as: ABC1, ABCA1, CERP
Function
Catalyzes the translocation of specific phospholipids from the cytoplasmic to the extracellular/lumenal leaflet of membrane coupled to the hydrolysis of ATP. Thereby, participates in phospholipid transfer to apolipoproteins to form nascent high density lipoproteins/HDLs. Transports preferentially phosphatidylcholine over phosphatidylserine. May play a similar role in the efflux of intracellular cholesterol to apolipoproteins and the formation of nascent high density lipoproteins/HDLs. Translocates phospholipids from the outer face of the plasma membrane and forces it through its gateway and annulus into an elongated hydrophobic tunnel in its extracellular domain.
Classification
- Family (Pfam)
- PF12698 ABC2_membrane_3, PF00005 ABC_tran, PF26955 ACT_13, PF23321 R1_ABCA1
- InterPro
- AAA+_ATPase, ABC2_TM, ABC_transporter-like_ATP-bd, ABC_transporter-like_CS, ABCA, P-loop_NTPase, R2_ABCA1-4-like
- Functional cluster
- Immunoglobulin-Domain Cell Adhesion Proteins
Experimental structures · PDB · 7
A predicted model is available from AlphaFold.
Gene Ontology · 65
- GO:0016323 basolateral plasma membrane
- GO:0030139 endocytic vesicle
- GO:0005789 endoplasmic reticulum membrane
- GO:0005768 endosome
- GO:0009897 external side of plasma membrane
- GO:0005794 Golgi apparatus
- GO:0097708 intracellular vesicle
- GO:0045121 membrane raft
- GO:0048471 perinuclear region of cytoplasm
- GO:0045335 phagocytic vesicle
- GO:0005886 plasma membrane
- GO:0140359 ABC-type transporter activity
- GO:0034186 apolipoprotein A-I binding
- GO:0034188 apolipoprotein A-I receptor activity
- GO:0034185 apolipoprotein binding
- GO:0005524 ATP binding
- GO:0016887 ATP hydrolysis activity
- GO:0051117 ATPase binding
- GO:0042626 ATPase-coupled transmembrane transporter activity
- GO:0015485 cholesterol binding
- GO:0120020 cholesterol transfer activity
- GO:0140328 floppase activity
- GO:0008035 high-density lipoprotein particle binding
- GO:0031210 phosphatidylcholine binding
- GO:0090554 phosphatidylcholine floppase activity
- GO:0090556 phosphatidylserine floppase activity
- GO:0005548 phospholipid transporter activity
- GO:0008320 protein transmembrane transporter activity
- GO:0005102 signaling receptor binding
- GO:0031267 small GTPase binding
- GO:0046623 sphingolipid floppase activity
- GO:0019905 syntaxin binding
- GO:0007189 adenylate cyclase-activating G protein-coupled receptor signaling pathway
- GO:0071397 cellular response to cholesterol
- GO:0071345 cellular response to cytokine stimulus
- GO:0071222 cellular response to lipopolysaccharide
- GO:0071404 cellular response to low-density lipoprotein particle stimulus
- GO:0071300 cellular response to retinoic acid
- GO:0071466 cellular response to xenobiotic stimulus
- GO:0033344 cholesterol efflux
- GO:0042632 cholesterol homeostasis
- GO:0008203 cholesterol metabolic process
- GO:0016197 endosomal transport
- GO:0140115 export across plasma membrane
- GO:0007186 G protein-coupled receptor signaling pathway
- GO:0034380 high-density lipoprotein particle assembly
- GO:0032367 intracellular cholesterol transport
- GO:0042158 lipoprotein biosynthetic process
- GO:0007040 lysosome organization
- GO:0010887 negative regulation of cholesterol storage
- GO:0010745 negative regulation of macrophage derived foam cell differentiation
- GO:0033700 phospholipid efflux
- GO:0055091 phospholipid homeostasis
- GO:0045332 phospholipid translocation
- GO:0060155 platelet dense granule organization
- GO:0010875 positive regulation of cholesterol efflux
- GO:0090108 positive regulation of high-density lipoprotein particle assembly
- GO:0009306 protein secretion
- GO:0071806 protein transmembrane transport
- GO:0032489 regulation of Cdc42 protein signal transduction
- GO:0090107 regulation of high-density lipoprotein particle assembly
- GO:0034616 response to laminar fluid shear stress
- GO:0033552 response to vitamin B3
- GO:0043691 reverse cholesterol transport
- GO:0023061 signal release
Disease associations
- Tangier disease MONDO:0008783
- hypoalphalipoproteinemia, primary, 1 MONDO:0011393
Drugs targeting this protein · 1
- PROBUCOL inhibitor
Related proteins · sequence + function similarity
- Phospholipid-transporting ATPase ABCA1 0.99
- Retinal-specific phospholipid-transporting ATPase ABCA4 0.93
- Retinal-specific phospholipid-transporting ATPase ABCA4 0.93
- Retinal-specific phospholipid-transporting ATPase ABCA4 0.92
- ATP-binding cassette sub-family A member 2 0.81
- ATP-binding cassette sub-family A member 2 0.77
- ATP-binding cassette sub-family A member 2 0.76
- Phospholipid-transporting ATPase ABCA3 0.70
- ATP-binding cassette sub-family A member 7 0.69
- Phospholipid-transporting ATPase ABCA3 0.69
- Phospholipid-transporting ATPase ABCA3 0.69
- ATP-binding cassette sub-family A member 7 0.68
Co-cited proteins · studied together in the literature
- Phospholipid-transporting ATPase ABCA1 3 shared papers
- Zinc finger protein 202 1 shared papers
- Protein NipSnap homolog 3B 1 shared papers
- 3-hydroxy-3-methylglutaryl-coenzyme A reductase 1 shared papers
- Palmitoyltransferase ZDHHC8 1 shared papers
- Glucosylceramide transporter ABCA12 1 shared papers
- ATP-binding cassette sub-family G member 1 2 shared papers
- Oxysterols receptor LXR-beta 1 shared papers
- Apolipoprotein E 2 shared papers
- ABC-type organic anion transporter ABCA8 1 shared papers
- Phospholipid-transporting ATPase ABCA7 1 shared papers
- Retinal-specific phospholipid-transporting ATPase ABCA4 1 shared papers
Literature · 52 cited papers
- ABCA1 is an extracellular phospholipid translocase. Nat. Commun. · 2022
- ABCA8 Regulates Cholesterol Efflux and High-Density Lipoprotein Cholesterol Levels. Arterioscler. Thromb. Vasc. Biol. · 2017
- Analysis of protein-coding genetic variation in 60,706 humans. Nature · 2016
- An enzyme assisted RP-RPLC approach for in-depth analysis of human liver phosphoproteome. J. Proteomics · 2014
- Differential phospholipid substrates and directional transport by ATP-binding cassette proteins ABCA1, ABCA7, and ABCA4 and disease-causing mutants. J. Biol. Chem. · 2013
- ABCA12 regulates ABCA1-dependent cholesterol efflux from macrophages and the development of atherosclerosis. Cell Metab. · 2013
- Palmitoylation of ATP-binding cassette transporter A1 is essential for its trafficking and function. Circ. Res. · 2009
- Formation of two intramolecular disulfide bonds is necessary for ApoA-I-dependent cholesterol efflux mediated by ABCA1. J. Biol. Chem. · 2009
- Glycoproteomics analysis of human liver tissue by combination of multiple enzyme digestion and hydrazide chemistry. J. Proteome Res. · 2009
- ABCA1 mutants reveal an interdependency between lipid export function, apoA-I binding activity, and Janus kinase 2 activation. J. Lipid Res. · 2009
- Polymorphisms associated with cholesterol and risk of cardiovascular events. N. Engl. J. Med. · 2008
- Cooperation between engulfment receptors: the case of ABCA1 and MEGF10. PLoS ONE · 2006
- … and 40 more in the literature graph
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