ABCA1

UniProt ID: O95477
Organism: Homo sapiens
Review Status: COMPLETE
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Gene Description

ABCA1 encodes a large ATP-binding cassette subfamily A multipass membrane transporter that uses ATP binding and hydrolysis to move phospholipids across membrane leaflets and to support cholesterol/phospholipid efflux to apolipoproteins. It localizes mainly to the plasma membrane and cell surface with endosomal/vesicular trafficking, binds apoA-I and other exchangeable apolipoproteins including apoE, and promotes nascent HDL particle formation, reverse cholesterol transport, and cellular lipid homeostasis. Loss of ABCA1 function causes Tangier disease and familial HDL deficiency, and in brain-relevant lipid biology ABCA1 is important for APOE lipidation and cholesterol handling.

Existing Annotations Review

GO Term Evidence Action Reason
GO:0042626 ATPase-coupled transmembrane transporter activity
IBA
GO_REF:0000033 		ACCEPT
Summary: ABCA1 couples ATP hydrolysis to vectorial transmembrane movement of lipid substrates; the active-transporter MF correctly captures its primary mechanism.
Reason: ATP-coupled active transport of lipids.
GO:0033700 phospholipid efflux
IBA
GO_REF:0000033 		ACCEPT
Summary: ABCA1 effluxes phospholipid (chiefly PC) to apolipoproteins, the proximal output of its floppase activity and required for HDL particle formation (IDA/IGI/IMP).
Reason: Core BP downstream of floppase activity.
GO:0090554 phosphatidylcholine floppase activity
IBA
GO_REF:0000033 		ACCEPT
Summary: ABCA1 preferentially flops phosphatidylcholine to the outer leaflet; PC is its favored substrate and most strongly stimulates its ATPase (IDA/IMP).
Reason: PC is the preferred floppase substrate.
GO:0090556 phosphatidylserine floppase activity
IBA
GO_REF:0000033 		ACCEPT
Summary: ABCA1 also translocates phosphatidylserine to the outer leaflet, less efficiently than PC; PS floppase defect underlies the Scott-syndrome-associated variant.
Reason: Demonstrated PS floppase activity (IDA).
GO:0005524 ATP binding
IEA
GO_REF:0000002 		ACCEPT
Summary: ABCA1 has two nucleotide-binding cassettes that bind ATP; nucleotide binding/hydrolysis powers the conformational cycle driving lipid floppase activity (IDA-supported).
Reason: Two ABC/NBD domains; ATP binding is required for transport.
GO:0005768 endosome
IEA
GO_REF:0000044 		ACCEPT
Summary: ABCA1 cycles through the endosomal system between the cell surface and intracellular pools; endosomal localization is documented (IDA/IEA).
Reason: Part of ABCA1's recycling itinerary.
GO:0005886 plasma membrane
IEA
GO_REF:0000120 		ACCEPT
Summary: ABCA1 is a multi-pass plasma-membrane protein; the cell surface is where it docks apoA-I and effluxes lipid. Best-supported localization (n=17; IDA/IMP/TAS).
Reason: Primary site of lipid efflux.
GO:0015850 organic hydroxy compound transport
IEA
GO_REF:0000117 		MODIFY
Summary: Over-general parent; ABCA1's relevant hydroxy-compound cargo is sterol, so the specific cholesterol transport term better captures its activity (IEA).
Reason: Generic parent; cholesterol is the specific cargo.
Proposed replacements: cholesterol transport
GO:0016020 membrane
IEA
GO_REF:0000120 		ACCEPT
Summary: ABCA1 is an integral membrane protein; the generic membrane CC is correct though less informative than its plasma-membrane localization (IEA).
Reason: Integral membrane protein.
GO:0016887 ATP hydrolysis activity
IEA
GO_REF:0000002 		ACCEPT
Summary: ABC ATPase that hydrolyzes ATP to ADP+Pi to energize lipid translocation; ATPase activity is modulated by phospholipid (stimulatory) and cholesterol/ceramide (inhibitory) substrates.
Reason: ATP hydrolysis powers the floppase transport cycle.
GO:0038027 apolipoprotein A-I-mediated signaling pathway
IEA
GO_REF:0000108 		KEEP AS NON CORE
Summary: ApoA-I docking on ABCA1 triggers intracellular signaling (JAK2/STAT3), a regulatory output downstream of the core lipid-acceptor interaction (IEA).
Reason: Downstream signaling from apoA-I engagement.
GO:0045332 phospholipid translocation
IEA
GO_REF:0000117 		ACCEPT
Summary: ABCA1 translocates phospholipids between membrane leaflets, the molecular event underlying its floppase/efflux function (IDA/IEA).
Reason: Inter-leaflet phospholipid translocation.
GO:0055085 transmembrane transport
IEA
GO_REF:0000002 		MODIFY
Summary: Bare transmembrane transport is uninformative for ABCA1; its substrates are lipids, so lipid transport is the appropriate, defensible specific term (IEA).
Reason: Generic; ABCA1 transports lipids specifically.
Proposed replacements: lipid transport
GO:0090554 phosphatidylcholine floppase activity
IEA
GO_REF:0000116 		ACCEPT
Summary: ABCA1 preferentially flops phosphatidylcholine to the outer leaflet; PC is its favored substrate and most strongly stimulates its ATPase (IDA/IMP).
Reason: PC is the preferred floppase substrate.
GO:0090556 phosphatidylserine floppase activity
IEA
GO_REF:0000116 		ACCEPT
Summary: ABCA1 also translocates phosphatidylserine to the outer leaflet, less efficiently than PC; PS floppase defect underlies the Scott-syndrome-associated variant.
Reason: Demonstrated PS floppase activity (IDA).
GO:0099039 sphingolipid translocation
IEA
GO_REF:0000108 		ACCEPT
Summary: ABCA1 translocates sphingomyelin/sphingolipid across the membrane, consistent with its measured sphingolipid floppase activity (IEA).
Reason: Sphingolipid inter-leaflet translocation.
GO:0140326 ATPase-coupled intramembrane lipid carrier activity
IEA
GO_REF:0000120 		ACCEPT
Summary: Directly measured EC 7.6.2.1 activity: ATP-coupled translocation of phospholipids across the membrane bilayer, the proximal molecular activity of ABCA1 (EXP/IDA evidence).
Reason: Defining floppase MF; experimentally demonstrated.
GO:0140359 ABC-type transporter activity
IEA
GO_REF:0000002 		ACCEPT
Summary: ABCA1 is a member of the ABC transporter superfamily that uses ATP binding/hydrolysis to drive transmembrane lipid translocation; the family-level MF is correct and central.
Reason: Bona fide ABC transporter; ATP-driven lipid translocase.
GO:0005515 protein binding
IPI
PMID:12084722
Naturally occurring mutations in the largest extracellular l... 		MARK AS OVER ANNOTATED
Summary: Generic 'protein binding' (n=9 IPI) conveys no specific function; ABCA1's informative interactions (apoA-I, syntaxin, CDC42, ABCA8) are captured by specific terms.
Reason: Uninformative; superseded by specific binding terms.
GO:0005515 protein binding
IPI
PMID:15469992
Association of ABCA1 with syntaxin 13 and flotillin-1 and en... 		MARK AS OVER ANNOTATED
Summary: Generic 'protein binding' (n=9 IPI) conveys no specific function; ABCA1's informative interactions (apoA-I, syntaxin, CDC42, ABCA8) are captured by specific terms.
Reason: Uninformative; superseded by specific binding terms.
GO:0005515 protein binding
IPI
PMID:16192269
Purification of ATP-binding cassette transporter A1 and asso... 		MARK AS OVER ANNOTATED
Summary: Generic 'protein binding' (n=9 IPI) conveys no specific function; ABCA1's informative interactions (apoA-I, syntaxin, CDC42, ABCA8) are captured by specific terms.
Reason: Uninformative; superseded by specific binding terms.
GO:0005515 protein binding
IPI
PMID:16443932
Apolipoprotein A-I activates Cdc42 signaling through the ABC... 		MARK AS OVER ANNOTATED
Summary: Generic 'protein binding' (n=9 IPI) conveys no specific function; ABCA1's informative interactions (apoA-I, syntaxin, CDC42, ABCA8) are captured by specific terms.
Reason: Uninformative; superseded by specific binding terms.
GO:0005515 protein binding
IPI
PMID:23931754
ABCA12 regulates ABCA1-dependent cholesterol efflux from mac... 		MARK AS OVER ANNOTATED
Summary: Generic 'protein binding' (n=9 IPI) conveys no specific function; ABCA1's informative interactions (apoA-I, syntaxin, CDC42, ABCA8) are captured by specific terms.
Reason: Uninformative; superseded by specific binding terms.
GO:0005515 protein binding
IPI
PMID:25170080
HIV-1 protein Nef inhibits activity of ATP-binding cassette ... 		MARK AS OVER ANNOTATED
Summary: Generic 'protein binding' (n=9 IPI) conveys no specific function; ABCA1's informative interactions (apoA-I, syntaxin, CDC42, ABCA8) are captured by specific terms.
Reason: Uninformative; superseded by specific binding terms.
GO:0005515 protein binding
IPI
PMID:30458687
Apolipoprotein A-I directly interacts with extracellular dom... 		MARK AS OVER ANNOTATED
Summary: Generic 'protein binding' (n=9 IPI) conveys no specific function; ABCA1's informative interactions (apoA-I, syntaxin, CDC42, ABCA8) are captured by specific terms.
Reason: Uninformative; superseded by specific binding terms.
GO:0005515 protein binding
IPI
PMID:36115835
Quantitative fragmentomics allow affinity mapping of interac... 		MARK AS OVER ANNOTATED
Summary: Generic 'protein binding' (n=9 IPI) conveys no specific function; ABCA1's informative interactions (apoA-I, syntaxin, CDC42, ABCA8) are captured by specific terms.
Reason: Uninformative; superseded by specific binding terms.
GO:0005794 Golgi apparatus
IEA
GO_REF:0000107 		KEEP AS NON CORE
Summary: ABCA1 transits the Golgi during biosynthesis/maturation; this is a secondary biosynthetic-trafficking location, not its functional efflux site (IEA).
Reason: Secretory-pathway transit location.
GO:0007584 response to nutrient
IEA
GO_REF:0000107 		KEEP AS NON CORE
Summary: ABCA1 expression responds to nutrient/lipid availability as part of metabolic regulation, upstream of its efflux activity (IEA).
Reason: Nutrient-responsive regulation of expression.
GO:0008035 high-density lipoprotein particle binding
IEA
GO_REF:0000107 		KEEP AS NON CORE
Summary: ABCA1 interacts with HDL particles during/after lipidation; binding mature HDL is a peripheral aspect relative to its nascent-particle assembly role (IEA).
Reason: Peripheral to core nascent-HDL assembly.
GO:0008320 transmembrane protein transporter activity
IEA
GO_REF:0000107 		MODIFY
Summary: ABCA1 does not transport proteins; the MF should be its ATP-coupled intramembrane lipid (floppase) transporter activity (IEA/ISS).
Reason: Wrong cargo; ABCA1 is a lipid floppase.
GO:0009306 protein secretion
IEA
GO_REF:0000107 		KEEP AS NON CORE
Summary: ABCA1 has been linked to secretion of certain proteins, a pleiotropic/indirect role distinct from its lipid-floppase function (IEA/IMP/ISS).
Reason: Pleiotropic secretion role, non-core.
GO:0009410 response to xenobiotic stimulus
IEA
GO_REF:0000107 		KEEP AS NON CORE
Summary: Organism/cell-level responsiveness to xenobiotics modulates ABCA1; contextual regulation distinct from its lipid-efflux function (IEA).
Reason: Contextual regulation, non-core.
GO:0009897 external side of plasma membrane
IEA
GO_REF:0000107 		ACCEPT
Summary: ABCA1's large extracellular domains, including the lipid tunnel/gateway, face the external leaflet where lipid is presented to apoA-I (IEA).
Reason: Extracellular lipid-presenting domains.
GO:0009986 cell surface
IEA
GO_REF:0000107 		ACCEPT
Summary: ABCA1 is presented at the cell surface where it engages apoA-I; surface localization requires palmitoylation and is essential for function (IEA).
Reason: Surface presentation for apoA-I docking.
GO:0010875 positive regulation of cholesterol efflux
IEA
GO_REF:0000107 		ACCEPT
Summary: ABCA1 is the principal positive effector of apoA-I-dependent cholesterol efflux from cells; this is a direct consequence of its transporter function (IEA).
Reason: Positive effector of cholesterol efflux.
GO:0015914 phospholipid transport
IEA
GO_REF:0000107 		ACCEPT
Summary: ABCA1 transports phospholipid out of the cell onto apolipoproteins; phospholipid transport is a direct output of its activity (IEA).
Reason: Exports phospholipid onto apolipoproteins.
GO:0016323 basolateral plasma membrane
IEA
GO_REF:0000107 		ACCEPT
Summary: In polarized cells ABCA1 localizes to the basolateral plasma-membrane domain consistent with directional lipid efflux (IEA).
Reason: Polarized PM domain for efflux.
GO:0023061 signal release
IEA
GO_REF:0000107 		KEEP AS NON CORE
Summary: ABCA1 contributes to release of signaling molecules in some contexts, an accessory role downstream of/parallel to lipid efflux (IEA/IMP/ISS).
Reason: Accessory signaling-release role.
GO:0030301 cholesterol transport
IEA
GO_REF:0000107 		ACCEPT
Summary: ABCA1 transports cholesterol across the plasma membrane to extracellular apolipoprotein acceptors; sterol transport is part of its core activity (IEA).
Reason: Transports cholesterol to apoA-I.
GO:0031667 response to nutrient levels
IEA
GO_REF:0000107 		KEEP AS NON CORE
Summary: ABCA1 is regulated by cellular nutrient/lipid status; a metabolic-response context rather than a core molecular role (IEA).
Reason: Metabolic-status regulation, non-core.
GO:0033552 response to vitamin B3
IEA
GO_REF:0000107 		KEEP AS NON CORE
Summary: Niacin (vitamin B3) raises HDL partly via ABCA1; a pharmacological-response context downstream of its regulation (IEA).
Reason: Pharmacological niacin response, non-core.
GO:0042158 lipoprotein biosynthetic process
IEA
GO_REF:0000107 		ACCEPT
Summary: ABCA1-mediated lipidation of apoA-I is the biosynthetic step that generates nascent HDL lipoprotein particles (IEA).
Reason: Generates nascent HDL lipoprotein.
GO:0042626 ATPase-coupled transmembrane transporter activity
IEA
GO_REF:0000107 		ACCEPT
Summary: ABCA1 couples ATP hydrolysis to vectorial transmembrane movement of lipid substrates; the active-transporter MF correctly captures its primary mechanism.
Reason: ATP-coupled active transport of lipids.
GO:0043691 reverse cholesterol transport
IEA
GO_REF:0000107 		ACCEPT
Summary: By generating nascent HDL from peripheral-cell cholesterol, ABCA1 initiates reverse cholesterol transport that returns cholesterol to the liver (IMP).
Reason: Initiates the RCT pathway.
GO:0071222 cellular response to lipopolysaccharide
IEA
GO_REF:0000107 		KEEP AS NON CORE
Summary: LPS induces ABCA1 expression via an LXR-independent pathway (PubMed:12032171); an inducible-response context distinct from transport (IEA).
Reason: LPS-inducible expression, non-core.
GO:0071300 cellular response to retinoic acid
IEA
GO_REF:0000107 		KEEP AS NON CORE
Summary: ABCA1 expression responds to retinoic-acid/RXR signaling; a transcriptional-regulation context rather than its core activity (IEA).
Reason: Transcriptional response to retinoid.
GO:0071345 cellular response to cytokine stimulus
IEA
GO_REF:0000107 		KEEP AS NON CORE
Summary: ABCA1 expression is modulated by cytokine signaling in inflammatory contexts; a transcriptional-response effect, not its transport function (IEA).
Reason: Inflammatory regulation of expression.
GO:0071397 cellular response to cholesterol
IEA
GO_REF:0000107 		KEEP AS NON CORE
Summary: ABCA1 expression/activity responds to cellular cholesterol load (via LXR), a regulatory response upstream of, not part of, its transport mechanism (IEA).
Reason: Regulatory response to sterol load.
GO:0071466 cellular response to xenobiotic stimulus
IEA
GO_REF:0000107 		KEEP AS NON CORE
Summary: ABCA1 levels respond to xenobiotic exposure (nuclear-receptor-mediated); a regulatory response, not its transport mechanism (IEA).
Reason: Regulatory response to xenobiotics.
GO:0071806 protein transmembrane transport
IEA
GO_REF:0000107 		MODIFY
Summary: ABCA1 is a lipid floppase, not a protein transporter; this IEA/ISS-propagated term should be recast as phospholipid efflux, its actual exported cargo.
Reason: Mis-propagated; ABCA1 effluxes phospholipid, not protein.
Proposed replacements: phospholipid efflux
GO:0090108 positive regulation of high-density lipoprotein particle assembly
IEA
GO_REF:0000107 		ACCEPT
Summary: ABCA1 positively drives HDL assembly by supplying lipid to apoA-I; increased ABCA1 increases nascent-HDL production (IEA/ISS).
Reason: Positively drives nascent-HDL formation.
GO:0120014 phospholipid transfer activity
IEA
GO_REF:0000107 		ACCEPT
Summary: ABCA1 mediates transfer of phospholipid to apolipoprotein acceptors, the molecular step that lipidates apoA-I into nascent HDL (IGI/IEA).
Reason: Phospholipid transfer onto apolipoprotein acceptors.
GO:0120020 cholesterol transfer activity
IEA
GO_REF:0000107 		ACCEPT
Summary: ABCA1 promotes transfer of cholesterol to apoA-I as part of HDL biogenesis; cholesterol is a translocated substrate (RHEA:39051) effluxed alongside phospholipid (IDA).
Reason: Cholesterol transfer onto apoA-I in HDL assembly.
GO:0140115 export across plasma membrane
IEA
GO_REF:0000107 		ACCEPT
Summary: ABCA1 exports lipid cargo across the plasma membrane to extracellular acceptors; export directionality is intrinsic to its function (IEA/ISS).
Reason: Plasma-membrane export of lipid cargo.
GO:0120014 phospholipid transfer activity
IGI
PMID:28373057
Lysophosphatidylcholine export by human ABCA7. 		ACCEPT
Summary: ABCA1 mediates transfer of phospholipid to apolipoprotein acceptors, the molecular step that lipidates apoA-I into nascent HDL (IGI/IEA).
Reason: Phospholipid transfer onto apolipoprotein acceptors.
GO:0140326 ATPase-coupled intramembrane lipid carrier activity
IDA
PMID:28373057
Lysophosphatidylcholine export by human ABCA7. 		ACCEPT
Summary: Directly measured EC 7.6.2.1 activity: ATP-coupled translocation of phospholipids across the membrane bilayer, the proximal molecular activity of ABCA1 (EXP/IDA evidence).
Reason: Defining floppase MF; experimentally demonstrated.
GO:0005886 plasma membrane
IDA
GO_REF:0000052 		ACCEPT
Summary: ABCA1 is a multi-pass plasma-membrane protein; the cell surface is where it docks apoA-I and effluxes lipid. Best-supported localization (n=17; IDA/IMP/TAS).
Reason: Primary site of lipid efflux.
GO:0140326 ATPase-coupled intramembrane lipid carrier activity
EXP
PMID:24097981
Differential phospholipid substrates and directional transpo... 		ACCEPT
Summary: Directly measured EC 7.6.2.1 activity: ATP-coupled translocation of phospholipids across the membrane bilayer, the proximal molecular activity of ABCA1 (EXP/IDA evidence).
Reason: Defining floppase MF; experimentally demonstrated.
GO:0005886 plasma membrane
IMP
PMID:35974019
ABCA1 is an extracellular phospholipid translocase. 		ACCEPT
Summary: ABCA1 is a multi-pass plasma-membrane protein; the cell surface is where it docks apoA-I and effluxes lipid. Best-supported localization (n=17; IDA/IMP/TAS).
Reason: Primary site of lipid efflux.
GO:0033344 cholesterol efflux
IMP
PMID:35974019
ABCA1 is an extracellular phospholipid translocase. 		ACCEPT
Summary: ABCA1 mediates efflux of cellular cholesterol onto apoA-I, the rate-limiting step of HDL biogenesis; the most heavily supported BP for this gene (IDA/IGI/IMP, n=9).
Reason: Defining physiological process of ABCA1.
GO:0033700 phospholipid efflux
IMP
PMID:35974019
ABCA1 is an extracellular phospholipid translocase. 		ACCEPT
Summary: ABCA1 effluxes phospholipid (chiefly PC) to apolipoproteins, the proximal output of its floppase activity and required for HDL particle formation (IDA/IGI/IMP).
Reason: Core BP downstream of floppase activity.
GO:0090554 phosphatidylcholine floppase activity
IMP
PMID:35974019
ABCA1 is an extracellular phospholipid translocase. 		ACCEPT
Summary: ABCA1 preferentially flops phosphatidylcholine to the outer leaflet; PC is its favored substrate and most strongly stimulates its ATPase (IDA/IMP).
Reason: PC is the preferred floppase substrate.
GO:0140115 export across plasma membrane
ISS
PMID:29937375
Chlamydia pneumoniae Hijacks a Host Autoregulatory IL-1β Loo... 		ACCEPT
Summary: ABCA1 exports lipid cargo across the plasma membrane to extracellular acceptors; export directionality is intrinsic to its function (IEA/ISS).
Reason: Plasma-membrane export of lipid cargo.
GO:0033344 cholesterol efflux
IMP
PMID:25084135
MicroRNA-19b promotes macrophage cholesterol accumulation an... 		ACCEPT
Summary: ABCA1 mediates efflux of cellular cholesterol onto apoA-I, the rate-limiting step of HDL biogenesis; the most heavily supported BP for this gene (IDA/IGI/IMP, n=9).
Reason: Defining physiological process of ABCA1.
GO:0009306 protein secretion
IMP
PMID:11855831
The ATP binding cassette transporter A1 contributes to the s... 		KEEP AS NON CORE
Summary: ABCA1 has been linked to secretion of certain proteins, a pleiotropic/indirect role distinct from its lipid-floppase function (IEA/IMP/ISS).
Reason: Pleiotropic secretion role, non-core.
GO:0009306 protein secretion
ISS
PMID:29937375
Chlamydia pneumoniae Hijacks a Host Autoregulatory IL-1β Loo... 		KEEP AS NON CORE
Summary: ABCA1 has been linked to secretion of certain proteins, a pleiotropic/indirect role distinct from its lipid-floppase function (IEA/IMP/ISS).
Reason: Pleiotropic secretion role, non-core.
GO:0023061 signal release
IMP
PMID:11855831
The ATP binding cassette transporter A1 contributes to the s... 		KEEP AS NON CORE
Summary: ABCA1 contributes to release of signaling molecules in some contexts, an accessory role downstream of/parallel to lipid efflux (IEA/IMP/ISS).
Reason: Accessory signaling-release role.
GO:0005886 plasma membrane
IDA
PMID:28373057
Lysophosphatidylcholine export by human ABCA7. 		ACCEPT
Summary: ABCA1 is a multi-pass plasma-membrane protein; the cell surface is where it docks apoA-I and effluxes lipid. Best-supported localization (n=17; IDA/IMP/TAS).
Reason: Primary site of lipid efflux.
GO:0033344 cholesterol efflux
IGI
PMID:28373057
Lysophosphatidylcholine export by human ABCA7. 		ACCEPT
Summary: ABCA1 mediates efflux of cellular cholesterol onto apoA-I, the rate-limiting step of HDL biogenesis; the most heavily supported BP for this gene (IDA/IGI/IMP, n=9).
Reason: Defining physiological process of ABCA1.
GO:0033700 phospholipid efflux
IGI
PMID:28373057
Lysophosphatidylcholine export by human ABCA7. 		ACCEPT
Summary: ABCA1 effluxes phospholipid (chiefly PC) to apolipoproteins, the proximal output of its floppase activity and required for HDL particle formation (IDA/IGI/IMP).
Reason: Core BP downstream of floppase activity.
GO:0097708 intracellular vesicle
IDA
PMID:28373057
Lysophosphatidylcholine export by human ABCA7. 		ACCEPT
Summary: ABCA1 resides in intracellular vesicular compartments during its trafficking/recycling between PM and endosomes (IDA).
Reason: Trafficking/recycling vesicle pool.
GO:0005886 plasma membrane
IDA
PMID:19556522
Palmitoylation of ATP-binding cassette transporter A1 is ess... 		ACCEPT
Summary: ABCA1 is a multi-pass plasma-membrane protein; the cell surface is where it docks apoA-I and effluxes lipid. Best-supported localization (n=17; IDA/IMP/TAS).
Reason: Primary site of lipid efflux.
GO:0033344 cholesterol efflux
IMP
PMID:19556522
Palmitoylation of ATP-binding cassette transporter A1 is ess... 		ACCEPT
Summary: ABCA1 mediates efflux of cellular cholesterol onto apoA-I, the rate-limiting step of HDL biogenesis; the most heavily supported BP for this gene (IDA/IGI/IMP, n=9).
Reason: Defining physiological process of ABCA1.
GO:0033700 phospholipid efflux
IMP
PMID:19556522
Palmitoylation of ATP-binding cassette transporter A1 is ess... 		ACCEPT
Summary: ABCA1 effluxes phospholipid (chiefly PC) to apolipoproteins, the proximal output of its floppase activity and required for HDL particle formation (IDA/IGI/IMP).
Reason: Core BP downstream of floppase activity.
GO:0008320 transmembrane protein transporter activity
ISS
PMID:29937375
Chlamydia pneumoniae Hijacks a Host Autoregulatory IL-1β Loo... 		MODIFY
Summary: ABCA1 does not transport proteins; the MF should be its ATP-coupled intramembrane lipid (floppase) transporter activity (IEA/ISS).
Reason: Wrong cargo; ABCA1 is a lipid floppase.
GO:0023061 signal release
ISS
PMID:29937375
Chlamydia pneumoniae Hijacks a Host Autoregulatory IL-1β Loo... 		KEEP AS NON CORE
Summary: ABCA1 contributes to release of signaling molecules in some contexts, an accessory role downstream of/parallel to lipid efflux (IEA/IMP/ISS).
Reason: Accessory signaling-release role.
GO:0071806 protein transmembrane transport
ISS
PMID:29937375
Chlamydia pneumoniae Hijacks a Host Autoregulatory IL-1β Loo... 		MODIFY
Summary: ABCA1 is a lipid floppase, not a protein transporter; this IEA/ISS-propagated term should be recast as phospholipid efflux, its actual exported cargo.
Reason: Mis-propagated; ABCA1 effluxes phospholipid, not protein.
Proposed replacements: phospholipid efflux
GO:0034616 response to laminar fluid shear stress
IDA
PMID:15358760
Sterol-responsive element-binding protein (SREBP) 2 down-reg... 		KEEP AS NON CORE
Summary: Endothelial ABCA1 expression/activity responds to laminar shear stress, a vascular-context regulatory response distinct from core efflux (IDA).
Reason: Shear-stress regulation in vasculature.
GO:0071404 cellular response to low-density lipoprotein particle stimulus
NAS
PMID:15358760
Sterol-responsive element-binding protein (SREBP) 2 down-reg... 		KEEP AS NON CORE
Summary: ABCA1 responds to LDL-derived cholesterol loading by upregulation; a regulatory response context rather than its core efflux activity (NAS).
Reason: Regulatory response to LDL loading.
GO:0046623 sphingolipid floppase activity
IDA
PMID:24097981
Differential phospholipid substrates and directional transpo... 		ACCEPT
Summary: ABCA1 can translocate sphingomyelin/sphingolipid across the membrane; sphingomyelin is among its measured catalytic substrates (IDA).
Reason: Sphingolipid among catalytic floppase substrates.
GO:0090554 phosphatidylcholine floppase activity
IDA
PMID:24097981
Differential phospholipid substrates and directional transpo... 		ACCEPT
Summary: ABCA1 preferentially flops phosphatidylcholine to the outer leaflet; PC is its favored substrate and most strongly stimulates its ATPase (IDA/IMP).
Reason: PC is the preferred floppase substrate.
GO:0090556 phosphatidylserine floppase activity
IDA
PMID:24097981
Differential phospholipid substrates and directional transpo... 		ACCEPT
Summary: ABCA1 also translocates phosphatidylserine to the outer leaflet, less efficiently than PC; PS floppase defect underlies the Scott-syndrome-associated variant.
Reason: Demonstrated PS floppase activity (IDA).
GO:0033344 cholesterol efflux
IDA
PMID:16702602
Efflux of sphingomyelin, cholesterol, and phosphatidylcholin... 		ACCEPT
Summary: ABCA1 mediates efflux of cellular cholesterol onto apoA-I, the rate-limiting step of HDL biogenesis; the most heavily supported BP for this gene (IDA/IGI/IMP, n=9).
Reason: Defining physiological process of ABCA1.
GO:0090554 phosphatidylcholine floppase activity
IDA
PMID:16702602
Efflux of sphingomyelin, cholesterol, and phosphatidylcholin... 		ACCEPT
Summary: ABCA1 preferentially flops phosphatidylcholine to the outer leaflet; PC is its favored substrate and most strongly stimulates its ATPase (IDA/IMP).
Reason: PC is the preferred floppase substrate.
GO:0140328 floppase activity
IDA
PMID:16702602
Efflux of sphingomyelin, cholesterol, and phosphatidylcholin... 		ACCEPT
Summary: ABCA1 acts as a floppase, moving phospholipids from the cytoplasmic to the exoplasmic leaflet of the plasma membrane prior to transfer onto apoA-I (IDA).
Reason: Floppase mechanism is the core transport mode.
GO:0031210 phosphatidylcholine binding
IDA
PMID:24097981
Differential phospholipid substrates and directional transpo... 		ACCEPT
Summary: ABCA1 binds phosphatidylcholine, its preferred transport substrate that engages the extracellular tunnel/gateway domain during translocation (IDA).
Reason: Substrate binding for the preferred PC cargo.
GO:0140328 floppase activity
IDA
PMID:24097981
Differential phospholipid substrates and directional transpo... 		ACCEPT
Summary: ABCA1 acts as a floppase, moving phospholipids from the cytoplasmic to the exoplasmic leaflet of the plasma membrane prior to transfer onto apoA-I (IDA).
Reason: Floppase mechanism is the core transport mode.
GO:0090108 positive regulation of high-density lipoprotein particle assembly
ISS
GO_REF:0000024 		ACCEPT
Summary: ABCA1 positively drives HDL assembly by supplying lipid to apoA-I; increased ABCA1 increases nascent-HDL production (IEA/ISS).
Reason: Positively drives nascent-HDL formation.
GO:0005768 endosome
IDA
PMID:24097981
Differential phospholipid substrates and directional transpo... 		ACCEPT
Summary: ABCA1 cycles through the endosomal system between the cell surface and intracellular pools; endosomal localization is documented (IDA/IEA).
Reason: Part of ABCA1's recycling itinerary.
GO:0005886 plasma membrane
IDA
PMID:24097981
Differential phospholipid substrates and directional transpo... 		ACCEPT
Summary: ABCA1 is a multi-pass plasma-membrane protein; the cell surface is where it docks apoA-I and effluxes lipid. Best-supported localization (n=17; IDA/IMP/TAS).
Reason: Primary site of lipid efflux.
GO:0005515 protein binding
IPI
PMID:14754908
Molecular interactions between apoE and ABCA1: impact on apo... 		MARK AS OVER ANNOTATED
Summary: Generic 'protein binding' (n=9 IPI) conveys no specific function; ABCA1's informative interactions (apoA-I, syntaxin, CDC42, ABCA8) are captured by specific terms.
Reason: Uninformative; superseded by specific binding terms.
GO:0034380 high-density lipoprotein particle assembly
IMP
PMID:14754908
Molecular interactions between apoE and ABCA1: impact on apo... 		ACCEPT
Summary: ABCA1-driven lipidation of apoA-I assembles nascent (pre-beta) HDL particles; loss of ABCA1 abolishes HDL, defining its role in particle assembly (IMP).
Reason: Builds nascent HDL particles.
GO:0007186 G protein-coupled receptor signaling pathway
IMP
PMID:16443932
Apolipoprotein A-I activates Cdc42 signaling through the ABC... 		KEEP AS NON CORE
Summary: ABCA1 modulates downstream signaling (e.g. via apoA-I engagement and Cdc42), but GPCR signaling is a secondary, indirect consequence of its lipid-transport role (IMP).
Reason: Indirect signaling effect, not core transport.
GO:0007189 adenylate cyclase-activating G protein-coupled receptor signaling pathway
IMP
PMID:14701824
Apolipoprotein A-I activates cellular cAMP signaling through... 		KEEP AS NON CORE
Summary: Reported adenylate-cyclase-coupled signaling is a downstream consequence of ABCA1/apoA-I interaction rather than its primary lipid-efflux activity (IMP).
Reason: Downstream signaling, secondary to efflux.
GO:0045121 membrane raft
IDA
PMID:15469992
Association of ABCA1 with syntaxin 13 and flotillin-1 and en... 		KEEP AS NON CORE
Summary: ABCA1 associates with/remodels membrane-raft lipid microdomains during efflux; raft localization is a contextual feature of its PM activity (IDA).
Reason: Lipid-microdomain context of efflux.
GO:0045332 phospholipid translocation
IDA
PMID:24097981
Differential phospholipid substrates and directional transpo... 		ACCEPT
Summary: ABCA1 translocates phospholipids between membrane leaflets, the molecular event underlying its floppase/efflux function (IDA/IEA).
Reason: Inter-leaflet phospholipid translocation.
GO:0042632 cholesterol homeostasis
TAS
PMID:24097981
Differential phospholipid substrates and directional transpo... 		ACCEPT
Summary: ABCA1 is a central regulator of cellular cholesterol balance, removing excess free cholesterol via efflux; defects cause massive tissue cholesteryl-ester deposition (IDA/TAS).
Reason: Removes excess cellular cholesterol.
GO:0090107 regulation of high-density lipoprotein particle assembly
TAS
PMID:24097981
Differential phospholipid substrates and directional transpo... 		ACCEPT
Summary: ABCA1 activity sets the rate of HDL particle assembly; its expression/activity is the principal control point for nascent-HDL formation (TAS).
Reason: Rate-limiting regulator of HDL assembly.
GO:0005886 plasma membrane
TAS
Reactome:R-HSA-5682111 		ACCEPT
Summary: ABCA1 is a multi-pass plasma-membrane protein; the cell surface is where it docks apoA-I and effluxes lipid. Best-supported localization (n=17; IDA/IMP/TAS).
Reason: Primary site of lipid efflux.
GO:0005789 endoplasmic reticulum membrane
TAS
Reactome:R-HSA-5682084 		KEEP AS NON CORE
Summary: ABCA1 is synthesized and folded in the ER membrane before trafficking to the cell surface; ER residence is biosynthetic, not its active site (TAS).
Reason: Biosynthetic ER stage, not functional site.
GO:0005789 endoplasmic reticulum membrane
TAS
Reactome:R-HSA-5682103 		KEEP AS NON CORE
Summary: ABCA1 is synthesized and folded in the ER membrane before trafficking to the cell surface; ER residence is biosynthetic, not its active site (TAS).
Reason: Biosynthetic ER stage, not functional site.
GO:0005886 plasma membrane
TAS
Reactome:R-HSA-216723 		ACCEPT
Summary: ABCA1 is a multi-pass plasma-membrane protein; the cell surface is where it docks apoA-I and effluxes lipid. Best-supported localization (n=17; IDA/IMP/TAS).
Reason: Primary site of lipid efflux.
GO:0005886 plasma membrane
TAS
Reactome:R-HSA-216727 		ACCEPT
Summary: ABCA1 is a multi-pass plasma-membrane protein; the cell surface is where it docks apoA-I and effluxes lipid. Best-supported localization (n=17; IDA/IMP/TAS).
Reason: Primary site of lipid efflux.
GO:0005886 plasma membrane
TAS
Reactome:R-HSA-216757 		ACCEPT
Summary: ABCA1 is a multi-pass plasma-membrane protein; the cell surface is where it docks apoA-I and effluxes lipid. Best-supported localization (n=17; IDA/IMP/TAS).
Reason: Primary site of lipid efflux.
GO:0005886 plasma membrane
TAS
Reactome:R-HSA-5682101 		ACCEPT
Summary: ABCA1 is a multi-pass plasma-membrane protein; the cell surface is where it docks apoA-I and effluxes lipid. Best-supported localization (n=17; IDA/IMP/TAS).
Reason: Primary site of lipid efflux.
GO:0005886 plasma membrane
TAS
Reactome:R-HSA-5682103 		ACCEPT
Summary: ABCA1 is a multi-pass plasma-membrane protein; the cell surface is where it docks apoA-I and effluxes lipid. Best-supported localization (n=17; IDA/IMP/TAS).
Reason: Primary site of lipid efflux.
GO:0051117 ATPase binding
IPI
PMID:23931754
ABCA12 regulates ABCA1-dependent cholesterol efflux from mac... 		MARK AS OVER ANNOTATED
Summary: Binding to another ATPase is too generic to describe ABCA1's molecular role and adds nothing beyond its specific partner interactions (IPI).
Reason: Generic enzyme-binding; uninformative.
GO:0005102 signaling receptor binding
IPI
PMID:23931754
ABCA12 regulates ABCA1-dependent cholesterol efflux from mac... 		MARK AS OVER ANNOTATED
Summary: Generic signaling-receptor binding does not specify a functional partnership; ABCA1's lipid-efflux role is not informatively captured by this term (IPI).
Reason: Uninformative generic binding term.
GO:0005886 plasma membrane
IDA
PMID:23931754
ABCA12 regulates ABCA1-dependent cholesterol efflux from mac... 		ACCEPT
Summary: ABCA1 is a multi-pass plasma-membrane protein; the cell surface is where it docks apoA-I and effluxes lipid. Best-supported localization (n=17; IDA/IMP/TAS).
Reason: Primary site of lipid efflux.
GO:0033344 cholesterol efflux
IDA
PMID:23931754
ABCA12 regulates ABCA1-dependent cholesterol efflux from mac... 		ACCEPT
Summary: ABCA1 mediates efflux of cellular cholesterol onto apoA-I, the rate-limiting step of HDL biogenesis; the most heavily supported BP for this gene (IDA/IGI/IMP, n=9).
Reason: Defining physiological process of ABCA1.
GO:0048471 perinuclear region of cytoplasm
IDA
PMID:23931754
ABCA12 regulates ABCA1-dependent cholesterol efflux from mac... 		KEEP AS NON CORE
Summary: ABCA1 is detected in the perinuclear region reflecting its biosynthetic/recycling intracellular pool rather than its functional surface location (IDA).
Reason: Intracellular biosynthetic/recycling pool.
GO:0005886 plasma membrane
TAS
Reactome:R-HSA-1989765 		ACCEPT
Summary: ABCA1 is a multi-pass plasma-membrane protein; the cell surface is where it docks apoA-I and effluxes lipid. Best-supported localization (n=17; IDA/IMP/TAS).
Reason: Primary site of lipid efflux.
GO:0005886 plasma membrane
TAS
Reactome:R-HSA-9618479 		ACCEPT
Summary: ABCA1 is a multi-pass plasma-membrane protein; the cell surface is where it docks apoA-I and effluxes lipid. Best-supported localization (n=17; IDA/IMP/TAS).
Reason: Primary site of lipid efflux.
GO:0005886 plasma membrane
TAS
Reactome:R-HSA-9619756 		ACCEPT
Summary: ABCA1 is a multi-pass plasma-membrane protein; the cell surface is where it docks apoA-I and effluxes lipid. Best-supported localization (n=17; IDA/IMP/TAS).
Reason: Primary site of lipid efflux.
GO:0032489 regulation of Cdc42 protein signal transduction
IMP
PMID:16443932
Apolipoprotein A-I activates Cdc42 signaling through the ABC... 		KEEP AS NON CORE
Summary: ABCA1/apoA-I engagement regulates Cdc42 GTPase signaling affecting cytoskeleton/membrane dynamics; a downstream signaling output of efflux (IMP).
Reason: Downstream Cdc42 signaling from apoA-I engagement.
GO:0019905 syntaxin binding
IPI
PMID:15469992
Association of ABCA1 with syntaxin 13 and flotillin-1 and en... 		KEEP AS NON CORE
Summary: ABCA1 binds syntaxin-12 (STX12), implicating SNARE-mediated trafficking in its recycling; a specific trafficking interaction, not core MF (IPI).
Reason: STX12 interaction supports trafficking.
GO:0010745 negative regulation of macrophage derived foam cell differentiation
TAS
PMID:18490524
Reduced expression of ATP-binding cassette transporter G1 in... 		KEEP AS NON CORE
Summary: By effluxing cholesterol from macrophages, ABCA1 prevents foam-cell formation; an important but downstream physiological consequence of efflux (TAS).
Reason: Downstream of macrophage cholesterol efflux.
GO:0010887 negative regulation of cholesterol storage
TAS
PMID:18490524
Reduced expression of ATP-binding cassette transporter G1 in... 		ACCEPT
Summary: By effluxing cholesterol, ABCA1 limits intracellular cholesteryl-ester accumulation; ABCA1 loss leads to cholesterol-ester storage (Tangier) (TAS).
Reason: Efflux limits intracellular cholesterol storage.
GO:0034380 high-density lipoprotein particle assembly
IMP
PMID:10431236
Mutations in ABC1 in Tangier disease and familial high-densi... 		ACCEPT
Summary: ABCA1-driven lipidation of apoA-I assembles nascent (pre-beta) HDL particles; loss of ABCA1 abolishes HDL, defining its role in particle assembly (IMP).
Reason: Builds nascent HDL particles.
GO:0034380 high-density lipoprotein particle assembly
IMP
PMID:17305370
The C-terminal lipid-binding domain of apolipoprotein E is a... 		ACCEPT
Summary: ABCA1-driven lipidation of apoA-I assembles nascent (pre-beta) HDL particles; loss of ABCA1 abolishes HDL, defining its role in particle assembly (IMP).
Reason: Builds nascent HDL particles.
GO:0034185 apolipoprotein binding
IPI
PMID:11162594
Apolipoprotein specificity for lipid efflux by the human ABC... 		ACCEPT
Summary: ABCA1 binds apolipoprotein acceptors (apoA-I, and functionally apoE) to lipidate them; apolipoprotein binding is integral to HDL biogenesis (IPI).
Reason: Binds apolipoprotein acceptors for lipidation.
GO:0034186 apolipoprotein A-I binding
IPI
PMID:11162594
Apolipoprotein specificity for lipid efflux by the human ABC... 		ACCEPT
Summary: ABCA1 binds lipid-poor apoA-I, the obligate acceptor onto which it loads phospholipid and cholesterol; this interaction is essential for nascent-HDL formation (IPI).
Reason: ApoA-I is the lipid acceptor; binding is mechanistically core.
GO:0034186 apolipoprotein A-I binding
IPI
PMID:16443932
Apolipoprotein A-I activates Cdc42 signaling through the ABC... 		ACCEPT
Summary: ABCA1 binds lipid-poor apoA-I, the obligate acceptor onto which it loads phospholipid and cholesterol; this interaction is essential for nascent-HDL formation (IPI).
Reason: ApoA-I is the lipid acceptor; binding is mechanistically core.
GO:0034188 apolipoprotein A-I receptor activity
IDA
PMID:16443932
Apolipoprotein A-I activates Cdc42 signaling through the ABC... 		ACCEPT
Summary: ABCA1 functions as the cell-surface receptor for apoA-I, docking the acceptor to enable directed lipid efflux (IDA).
Reason: Receptor for the apoA-I lipid acceptor.
GO:0033344 cholesterol efflux
IDA
PMID:11162594
Apolipoprotein specificity for lipid efflux by the human ABC... 		ACCEPT
Summary: ABCA1 mediates efflux of cellular cholesterol onto apoA-I, the rate-limiting step of HDL biogenesis; the most heavily supported BP for this gene (IDA/IGI/IMP, n=9).
Reason: Defining physiological process of ABCA1.
GO:0033700 phospholipid efflux
IDA
PMID:11162594
Apolipoprotein specificity for lipid efflux by the human ABC... 		ACCEPT
Summary: ABCA1 effluxes phospholipid (chiefly PC) to apolipoproteins, the proximal output of its floppase activity and required for HDL particle formation (IDA/IGI/IMP).
Reason: Core BP downstream of floppase activity.
GO:0031267 small GTPase binding
IPI
PMID:16443932
Apolipoprotein A-I activates Cdc42 signaling through the ABC... 		KEEP AS NON CORE
Summary: ABCA1 binds CDC42 (a small GTPase), linking efflux to cytoskeletal signaling; a specific partner interaction peripheral to transport (IPI).
Reason: CDC42 interaction; peripheral signaling link.
GO:0033344 cholesterol efflux
IMP
PMID:16443932
Apolipoprotein A-I activates Cdc42 signaling through the ABC... 		ACCEPT
Summary: ABCA1 mediates efflux of cellular cholesterol onto apoA-I, the rate-limiting step of HDL biogenesis; the most heavily supported BP for this gene (IDA/IGI/IMP, n=9).
Reason: Defining physiological process of ABCA1.
GO:0042632 cholesterol homeostasis
IDA
PMID:10431236
Mutations in ABC1 in Tangier disease and familial high-densi... 		ACCEPT
Summary: ABCA1 is a central regulator of cellular cholesterol balance, removing excess free cholesterol via efflux; defects cause massive tissue cholesteryl-ester deposition (IDA/TAS).
Reason: Removes excess cellular cholesterol.
GO:0033700 phospholipid efflux
IMP
PMID:16702602
Efflux of sphingomyelin, cholesterol, and phosphatidylcholin... 		ACCEPT
Summary: ABCA1 effluxes phospholipid (chiefly PC) to apolipoproteins, the proximal output of its floppase activity and required for HDL particle formation (IDA/IGI/IMP).
Reason: Core BP downstream of floppase activity.
GO:0055091 phospholipid homeostasis
IMP
PMID:16702602
Efflux of sphingomyelin, cholesterol, and phosphatidylcholin... 		ACCEPT
Summary: By exporting membrane phospholipids to apolipoproteins, ABCA1 helps maintain cellular phospholipid balance (IMP).
Reason: Maintains cellular phospholipid balance via efflux.
GO:0015485 cholesterol binding
IC
PMID:12084722
Naturally occurring mutations in the largest extracellular l... 		ACCEPT
Summary: ABCA1 binds cholesterol, a substrate it exports; cholesterol also feedback-inhibits its ATPase activity (IC).
Reason: Cholesterol is a bound transport substrate.
GO:0033700 phospholipid efflux
IDA
PMID:10431236
Mutations in ABC1 in Tangier disease and familial high-densi... 		ACCEPT
Summary: ABCA1 effluxes phospholipid (chiefly PC) to apolipoproteins, the proximal output of its floppase activity and required for HDL particle formation (IDA/IGI/IMP).
Reason: Core BP downstream of floppase activity.
GO:0005524 ATP binding
IDA
PMID:11700048
Characterization of the ATPase cycle of human ABCA1: implica... 		ACCEPT
Summary: ABCA1 has two nucleotide-binding cassettes that bind ATP; nucleotide binding/hydrolysis powers the conformational cycle driving lipid floppase activity (IDA-supported).
Reason: Two ABC/NBD domains; ATP binding is required for transport.
GO:0005886 plasma membrane
IDA
PMID:10525055
The Tangier disease gene product ABC1 controls the cellular ... 		ACCEPT
Summary: ABCA1 is a multi-pass plasma-membrane protein; the cell surface is where it docks apoA-I and effluxes lipid. Best-supported localization (n=17; IDA/IMP/TAS).
Reason: Primary site of lipid efflux.
GO:0007040 lysosome organization
IDA
PMID:15163665
Impaired platelet activation in familial high density lipopr... 		KEEP AS NON CORE
Summary: ABCA1 influences lysosome organization linked to cellular lipid handling, a downstream cellular consequence rather than its transport function (IDA).
Reason: Downstream lipid-handling effect.
GO:0008203 cholesterol metabolic process
IDA
PMID:14747463
The ABCA1 transporter modulates late endocytic trafficking: ... 		ACCEPT
Summary: ABCA1 participates in cholesterol metabolism by exporting cellular cholesterol, shaping intracellular sterol pools (IDA).
Reason: Cholesterol export shapes sterol metabolism.
GO:0016197 endosomal transport
IDA
PMID:14747463
The ABCA1 transporter modulates late endocytic trafficking: ... 		KEEP AS NON CORE
Summary: ABCA1's endosomal recycling supports surface availability, a trafficking process supporting but distinct from its core efflux activity (IDA).
Reason: Supports surface recycling of ABCA1.
GO:0030139 endocytic vesicle
IDA
PMID:14747463
The ABCA1 transporter modulates late endocytic trafficking: ... 		ACCEPT
Summary: ABCA1 is found in endocytic vesicles as it recycles between the plasma membrane and endosomes (IDA).
Reason: Recycling endocytic compartment.
GO:0032367 intracellular cholesterol transport
IMP
PMID:10431236
Mutations in ABC1 in Tangier disease and familial high-densi... 		ACCEPT
Summary: ABCA1 contributes to mobilization/trafficking of intracellular cholesterol toward the plasma membrane for efflux (IMP).
Reason: Mobilizes intracellular cholesterol for efflux.
GO:0033344 cholesterol efflux
IDA
PMID:10431236
Mutations in ABC1 in Tangier disease and familial high-densi... 		ACCEPT
Summary: ABCA1 mediates efflux of cellular cholesterol onto apoA-I, the rate-limiting step of HDL biogenesis; the most heavily supported BP for this gene (IDA/IGI/IMP, n=9).
Reason: Defining physiological process of ABCA1.
GO:0043691 reverse cholesterol transport
IMP
PMID:10431236
Mutations in ABC1 in Tangier disease and familial high-densi... 		ACCEPT
Summary: By generating nascent HDL from peripheral-cell cholesterol, ABCA1 initiates reverse cholesterol transport that returns cholesterol to the liver (IMP).
Reason: Initiates the RCT pathway.
GO:0045335 phagocytic vesicle
IDA
PMID:15469992
Association of ABCA1 with syntaxin 13 and flotillin-1 and en... 		KEEP AS NON CORE
Summary: ABCA1 on phagocytic vesicles relates to its accessory role in apoptotic-cell engulfment, downstream of/parallel to lipid efflux (IDA).
Reason: Engulfment-related localization, non-core.
GO:0060155 platelet dense granule organization
IMP
PMID:15163665
Impaired platelet activation in familial high density lipopr... 		KEEP AS NON CORE
Summary: ABCA1 affects platelet dense-granule organization, a tissue-specific pleiotropic role separate from its central lipid-efflux function (IMP).
Reason: Pleiotropic platelet role, non-core.
GO:0120020 cholesterol transfer activity
IDA
PMID:12084722
Naturally occurring mutations in the largest extracellular l... 		ACCEPT
Summary: ABCA1 promotes transfer of cholesterol to apoA-I as part of HDL biogenesis; cholesterol is a translocated substrate (RHEA:39051) effluxed alongside phospholipid (IDA).
Reason: Cholesterol transfer onto apoA-I in HDL assembly.

Core Functions

ABCA1 uses ATP binding and hydrolysis to translocate phospholipids across membrane leaflets, with direct support for phosphatidylcholine, phosphatidylserine, and sphingomyelin movement and for extracellular phospholipid extraction at the plasma membrane.

Molecular Function:
ATPase-coupled intramembrane lipid transporter activity
Directly Involved In:
phospholipid translocation phospholipid efflux sphingolipid translocation
Cellular Locations:
plasma membrane cell surface endosome
Supporting Evidence:
  • file:human/ABCA1/ABCA1-uniprot.txt
    Catalyzes the translocation of specific phospholipids
  • PMID:24097981
    exported or flipped phosphatidylcholine, phosphatidylserine, and sphingomyelin
  • PMID:24097981
    The same phospholipids stimulated the ATPase activity of these ABCA transporters
  • PMID:35974019
    outer face of the plasma membrane and forces it through its gateway and annulus

ABCA1 binds apoA-I and other exchangeable apolipoproteins, including APOE, to drive cellular cholesterol and phospholipid efflux, nascent HDL particle assembly, and reverse cholesterol transport. This lipidation activity is the ABCA1 function most directly connected to APOE biology.

Molecular Function:
apolipoprotein A-I receptor activity
Directly Involved In:
cholesterol efflux high-density lipoprotein particle assembly reverse cholesterol transport positive regulation of high-density lipoprotein particle assembly cholesterol homeostasis
Cellular Locations:
plasma membrane cell surface endocytic vesicle
Supporting Evidence:

ABCA1 contributes to cholesterol movement out of cells and away from intracellular pools, limiting cholesterol storage and promoting HDL-associated lipid removal. This cholesterol-efflux role is supported by Tangier/familial HDL-deficiency genetics and cellular efflux assays, although the direct transported lipid substrate is best established for phospholipids.

Molecular Function:
cholesterol transfer activity
Directly Involved In:
cholesterol transport cholesterol efflux intracellular cholesterol transport negative regulation of cholesterol storage cholesterol metabolic process
Cellular Locations:
plasma membrane endosome
Supporting Evidence:

References

GO_REF:0000002
Gene Ontology annotation through association of InterPro records with GO terms
GO_REF:0000024
Manual transfer of experimentally-verified manual GO annotation data to orthologs by curator judgment of sequence similarity
GO_REF:0000033
Annotation inferences using phylogenetic trees
GO_REF:0000044
Gene Ontology annotation based on UniProtKB/Swiss-Prot Subcellular Location vocabulary mapping, accompanied by conservative changes to GO terms applied by UniProt
GO_REF:0000052
Gene Ontology annotation based on curation of immunofluorescence data
GO_REF:0000107
Automatic transfer of experimentally verified manual GO annotation data to orthologs using Ensembl Compara
GO_REF:0000108
Automatic assignment of GO terms using logical inference, based on on inter-ontology links
GO_REF:0000116
Automatic Gene Ontology annotation based on Rhea mapping
GO_REF:0000117
Electronic Gene Ontology annotations created by ARBA machine learning models
GO_REF:0000120
Combined Automated Annotation using Multiple IEA Methods
PMID:10431236
Mutations in ABC1 in Tangier disease and familial high-density lipoprotein deficiency.
PMID:10525055
The Tangier disease gene product ABC1 controls the cellular apolipoprotein-mediated lipid removal pathway.
PMID:11162594
Apolipoprotein specificity for lipid efflux by the human ABCAI transporter.
PMID:11700048
Characterization of the ATPase cycle of human ABCA1: implications for its function as a regulator rather than an active transporter.
PMID:11855831
The ATP binding cassette transporter A1 contributes to the secretion of interleukin 1beta from macrophages but not from monocytes.
PMID:12084722
Naturally occurring mutations in the largest extracellular loops of ABCA1 can disrupt its direct interaction with apolipoprotein A-I.
PMID:14701824
Apolipoprotein A-I activates cellular cAMP signaling through the ABCA1 transporter.
PMID:14747463
The ABCA1 transporter modulates late endocytic trafficking: insights from the correction of the genetic defect in Tangier disease.
PMID:14754908
Molecular interactions between apoE and ABCA1: impact on apoE lipidation.
PMID:15163665
Impaired platelet activation in familial high density lipoprotein deficiency (Tangier disease).
PMID:15358760
Sterol-responsive element-binding protein (SREBP) 2 down-regulates ATP-binding cassette transporter A1 in vascular endothelial cells: a novel role of SREBP in regulating cholesterol metabolism.
PMID:15469992
Association of ABCA1 with syntaxin 13 and flotillin-1 and enhanced phagocytosis in tangier cells.
PMID:16192269
Purification of ATP-binding cassette transporter A1 and associated binding proteins reveals the importance of beta1-syntrophin in cholesterol efflux.
PMID:16443932
Apolipoprotein A-I activates Cdc42 signaling through the ABCA1 transporter.
PMID:16702602
Efflux of sphingomyelin, cholesterol, and phosphatidylcholine by ABCG1.
PMID:17305370
The C-terminal lipid-binding domain of apolipoprotein E is a highly efficient mediator of ABCA1-dependent cholesterol efflux that promotes the assembly of high-density lipoproteins.
PMID:18490524
Reduced expression of ATP-binding cassette transporter G1 increases cholesterol accumulation in macrophages of patients with type 2 diabetes mellitus.
PMID:19556522
Palmitoylation of ATP-binding cassette transporter A1 is essential for its trafficking and function.
PMID:23931754
ABCA12 regulates ABCA1-dependent cholesterol efflux from macrophages and the development of atherosclerosis.
PMID:24097981
Differential phospholipid substrates and directional transport by ATP-binding cassette proteins ABCA1, ABCA7, and ABCA4 and disease-causing mutants.
PMID:25084135
MicroRNA-19b promotes macrophage cholesterol accumulation and aortic atherosclerosis by targeting ATP-binding cassette transporter A1.
PMID:25170080
HIV-1 protein Nef inhibits activity of ATP-binding cassette transporter A1 by targeting endoplasmic reticulum chaperone calnexin.
PMID:28373057
Lysophosphatidylcholine export by human ABCA7.
PMID:29937375
Chlamydia pneumoniae Hijacks a Host Autoregulatory IL-1β Loop to Drive Foam Cell Formation and Accelerate Atherosclerosis.
PMID:30458687
Apolipoprotein A-I directly interacts with extracellular domain 1 of human ABCA1.
PMID:35974019
ABCA1 is an extracellular phospholipid translocase.
PMID:36115835
Quantitative fragmentomics allow affinity mapping of interactomes.
Reactome:R-HSA-1989765
Expression of ABCA1
Reactome:R-HSA-216723
4xPALM-C-p-2S-ABCA1 tetramer transports CHOL from transport vesicle membrane to plasma membrane
Reactome:R-HSA-216727
4xPALM-C-p-2S-ABCA1 tetramer binds APOA1
Reactome:R-HSA-216757
4xPALM-C-p-2S-ABCA1 tetramer transports PL from transport vesicle membrane to plasma membrane
Reactome:R-HSA-5682084
ZDHCC8 transfers PALM from PALM-CoA to ABCA1 tetramer
Reactome:R-HSA-5682101
PKA phosphorylates 4xPALM-C-p-2S-ABCA1 tetramer
Reactome:R-HSA-5682103
4xPALM-C-ABCA1 tetramer translocates from ER membrane to plasma membrane
Reactome:R-HSA-5682111
Defective ABCA1 does not transport CHOL from transport vesicle membrane to plasma membrane
Reactome:R-HSA-9618479
ABCA1 mRNA is translated
Reactome:R-HSA-9619756
NR1H2 binds ABCA1
file:human/ABCA1/ABCA1-uniprot.txt
UniProt text export for ABCA1 (O95477)
file:human/ABCA1/ABCA1-notes.md
Manual ABCA1 review notes

Suggested Questions for Experts

Q: Which Alzheimer-relevant ABCA1 variants primarily impair apoE lipidation versus ATP-coupled phospholipid translocation, cell-surface localization, or endosomal trafficking?

Suggested experts: ABC transporter experts, Alzheimer lipid biology experts

Q: Should ABCA1 apoA-I-triggered Cdc42/cAMP signaling be curated as a secondary signaling branch, or only retained when directly tied to lipid efflux assays?

Suggested experts: GO signaling curators, lipid transport curators

Q: How should brain-cell-type ABCA1 activity be represented for astrocytes, microglia, neurons, and vascular cells when the strongest biochemical evidence comes from macrophage/fibroblast systems?

Suggested experts: neuroglia lipid metabolism experts, Alzheimer genetics experts

Suggested Experiments

Experiment: Measure apoE isoform lipidation, cholesterol efflux, and phospholipid export in endogenous human astrocyte and microglial ABCA1 knockout/rescue systems.

Hypothesis: ABCA1 Alzheimer-relevant effects are driven by coupled apoE lipidation and phospholipid/cholesterol efflux rather than by generic signaling outputs.

Type: endogenous brain-cell lipidation and efflux assay

Experiment: Separate ABCA1 phosphatidylcholine/phosphatidylserine/sphingomyelin translocation from cholesterol efflux using purified transporter reconstitution and matched cell-surface localization mutants.

Hypothesis: Direct phospholipid translocation is the proximal transporter activity that enables downstream cholesterol efflux and HDL particle assembly.

Type: reconstituted transporter and localization-mutant assay

📚 Additional Documentation

Notes

(ABCA1-notes.md)

ABCA1 review notes

Deep research status: just deep-research-falcon human ABCA1 --fallback perplexity-lite was launched after just fetch-gene human ABCA1 and just fetch-gene-pmids human ABCA1; it timed out after 180 seconds without writing a provider artifact. This note records the local evidence used for the first-pass GO review.

Core functional picture

ABCA1 is a multipass ABCA-family transporter whose defining function is ATP-coupled lipid movement at the plasma membrane/endosomal system. UniProt summarizes the molecular role as phospholipid translocation coupled to ATP hydrolysis [file:human/ABCA1/ABCA1-uniprot.txt "Catalyzes the translocation of specific phospholipids"] and apolipoprotein-dependent HDL biogenesis [file:human/ABCA1/ABCA1-uniprot.txt "transfer to apolipoproteins"]. Direct reconstitution assays support phosphatidylcholine, phosphatidylserine, and sphingomyelin transport PMID:24097981 and show lipid-stimulated ATPase activity PMID:24097981.

ABCA1-dependent HDL formation is tied to apoA-I and other exchangeable apolipoproteins. Tangier-disease studies show that loss or inhibition of ABC1 reduces apolipoprotein-mediated lipid efflux PMID:10525055 and place the protein at the plasma membrane PMID:10525055. ApoA-I extracellular-loop mutants impair cholesterol efflux and apoA-I interaction PMID:12084722 PMID:12084722. A later structural/mechanistic study supports extracellular phospholipid extraction/export PMID:35974019.

ABCA1 is also strongly tied to cholesterol efflux and apolipoprotein E lipidation. The original Tangier/familial HDL-deficiency genetics paper named ABC1/CERP for intracellular cholesterol transport PMID:10431236 PMID:10431236. ApoE can bind ABCA1 and induce cholesterol efflux, generating nascent apoE/cholesterol/phospholipid particles PMID:14754908 PMID:14754908. This supports Alzheimer-relevant ABCA1 placement in APOE lipidation and lipid homeostasis modules.

Annotation review decisions

Accept as core: ABC transporter/ATP binding and hydrolysis terms, ATPase-coupled transmembrane/lipid-carrier activity, floppase/phospholipid transfer terms, cholesterol transport/efflux/homeostasis, apoA-I/apolipoprotein binding or receptor activity, HDL assembly/reverse cholesterol transport, and direct plasma-membrane/endosomal membrane localizations.

Keep as non-core: experimentally plausible context terms such as apoA-I-triggered Cdc42/GPCR signaling, inflammatory/cytokine or LPS response, endothelial shear/LDL/nutrient response, ER/Golgi/perinuclear trafficking, lysosome or platelet dense-granule phenotypes, protein secretion/signal release, and phagocytic vesicle/membrane raft localization. These are credible ABCA1 biology but not the primary molecular function.

Mark as over-annotated: generic protein binding, broad signaling-receptor or ATPase-binding annotations, and other partner-binding labels that do not capture ABCA1's informative activity.

Modify: broad or misleading transport labels should be redirected to lipid-specific terms, especially cholesterol transport/transfer or phospholipid translocation/ATPase-coupled intramembrane lipid carrier activity.

2026-06-20 second-pass audit

The second-pass audit confirmed the existing ABCA1 review and manual reference metadata. No annotation action changes were needed: ABCA1 remains curated as an ATP-driven phospholipid/cholesterol transporter that enables apolipoprotein-dependent lipid efflux, HDL biogenesis, and APOE lipidation, with inflammatory, signaling, vesicle, secretion, trafficking, and generic binding annotations kept non-core or over-annotated unless they directly reflect lipid-transport biology.

📄 View Raw YAML

 
id: O95477
gene_symbol: ABCA1
product_type: PROTEIN
status: COMPLETE
taxon:
  id: NCBITaxon:9606
  label: Homo sapiens
description: 'ABCA1 encodes a large ATP-binding cassette subfamily A multipass membrane transporter that uses ATP binding and hydrolysis to move phospholipids across membrane leaflets and to support cholesterol/phospholipid efflux to apolipoproteins. It localizes mainly to the plasma membrane and cell surface with endosomal/vesicular trafficking, binds apoA-I and other exchangeable apolipoproteins including apoE, and promotes nascent HDL particle formation, reverse cholesterol transport, and cellular lipid homeostasis. Loss of ABCA1 function causes Tangier disease and familial HDL deficiency, and in brain-relevant lipid biology ABCA1 is important for APOE lipidation and cholesterol handling.'
existing_annotations:
- term:
    id: GO:0042626
    label: ATPase-coupled transmembrane transporter activity
  evidence_type: IBA
  original_reference_id: GO_REF:0000033
  qualifier: enables
  review:
    summary: ABCA1 couples ATP hydrolysis to vectorial transmembrane movement of lipid substrates; the active-transporter MF correctly captures its primary mechanism.
    action: ACCEPT
    reason: ATP-coupled active transport of lipids.
- term:
    id: GO:0033700
    label: phospholipid efflux
  evidence_type: IBA
  original_reference_id: GO_REF:0000033
  qualifier: involved_in
  review:
    summary: ABCA1 effluxes phospholipid (chiefly PC) to apolipoproteins, the proximal output of its floppase activity and required for HDL particle formation (IDA/IGI/IMP).
    action: ACCEPT
    reason: Core BP downstream of floppase activity.
- term:
    id: GO:0090554
    label: phosphatidylcholine floppase activity
  evidence_type: IBA
  original_reference_id: GO_REF:0000033
  qualifier: enables
  review:
    summary: ABCA1 preferentially flops phosphatidylcholine to the outer leaflet; PC is its favored substrate and most strongly stimulates its ATPase (IDA/IMP).
    action: ACCEPT
    reason: PC is the preferred floppase substrate.
- term:
    id: GO:0090556
    label: phosphatidylserine floppase activity
  evidence_type: IBA
  original_reference_id: GO_REF:0000033
  qualifier: enables
  review:
    summary: ABCA1 also translocates phosphatidylserine to the outer leaflet, less efficiently than PC; PS floppase defect underlies the Scott-syndrome-associated variant.
    action: ACCEPT
    reason: Demonstrated PS floppase activity (IDA).
- term:
    id: GO:0005524
    label: ATP binding
  evidence_type: IEA
  original_reference_id: GO_REF:0000002
  qualifier: enables
  review:
    summary: ABCA1 has two nucleotide-binding cassettes that bind ATP; nucleotide binding/hydrolysis powers the conformational cycle driving lipid floppase activity (IDA-supported).
    action: ACCEPT
    reason: Two ABC/NBD domains; ATP binding is required for transport.
- term:
    id: GO:0005768
    label: endosome
  evidence_type: IEA
  original_reference_id: GO_REF:0000044
  qualifier: located_in
  review:
    summary: ABCA1 cycles through the endosomal system between the cell surface and intracellular pools; endosomal localization is documented (IDA/IEA).
    action: ACCEPT
    reason: Part of ABCA1's recycling itinerary.
- term:
    id: GO:0005886
    label: plasma membrane
  evidence_type: IEA
  original_reference_id: GO_REF:0000120
  qualifier: located_in
  review:
    summary: ABCA1 is a multi-pass plasma-membrane protein; the cell surface is where it docks apoA-I and effluxes lipid. Best-supported localization (n=17; IDA/IMP/TAS).
    action: ACCEPT
    reason: Primary site of lipid efflux.
- term:
    id: GO:0015850
    label: organic hydroxy compound transport
  evidence_type: IEA
  original_reference_id: GO_REF:0000117
  qualifier: involved_in
  review:
    summary: Over-general parent; ABCA1's relevant hydroxy-compound cargo is sterol, so the specific cholesterol transport term better captures its activity (IEA).
    action: MODIFY
    reason: Generic parent; cholesterol is the specific cargo.
    proposed_replacement_terms:
    - id: GO:0030301
      label: cholesterol transport
- term:
    id: GO:0016020
    label: membrane
  evidence_type: IEA
  original_reference_id: GO_REF:0000120
  qualifier: located_in
  review:
    summary: ABCA1 is an integral membrane protein; the generic membrane CC is correct though less informative than its plasma-membrane localization (IEA).
    action: ACCEPT
    reason: Integral membrane protein.
- term:
    id: GO:0016887
    label: ATP hydrolysis activity
  evidence_type: IEA
  original_reference_id: GO_REF:0000002
  qualifier: enables
  review:
    summary: ABC ATPase that hydrolyzes ATP to ADP+Pi to energize lipid translocation; ATPase activity is modulated by phospholipid (stimulatory) and cholesterol/ceramide (inhibitory) substrates.
    action: ACCEPT
    reason: ATP hydrolysis powers the floppase transport cycle.
- term:
    id: GO:0038027
    label: apolipoprotein A-I-mediated signaling pathway
  evidence_type: IEA
  original_reference_id: GO_REF:0000108
  qualifier: involved_in
  review:
    summary: ApoA-I docking on ABCA1 triggers intracellular signaling (JAK2/STAT3), a regulatory output downstream of the core lipid-acceptor interaction (IEA).
    action: KEEP_AS_NON_CORE
    reason: Downstream signaling from apoA-I engagement.
- term:
    id: GO:0045332
    label: phospholipid translocation
  evidence_type: IEA
  original_reference_id: GO_REF:0000117
  qualifier: involved_in
  review:
    summary: ABCA1 translocates phospholipids between membrane leaflets, the molecular event underlying its floppase/efflux function (IDA/IEA).
    action: ACCEPT
    reason: Inter-leaflet phospholipid translocation.
- term:
    id: GO:0055085
    label: transmembrane transport
  evidence_type: IEA
  original_reference_id: GO_REF:0000002
  qualifier: involved_in
  review:
    summary: Bare transmembrane transport is uninformative for ABCA1; its substrates are lipids, so lipid transport is the appropriate, defensible specific term (IEA).
    action: MODIFY
    reason: Generic; ABCA1 transports lipids specifically.
    proposed_replacement_terms:
    - id: GO:0006869
      label: lipid transport
- term:
    id: GO:0090554
    label: phosphatidylcholine floppase activity
  evidence_type: IEA
  original_reference_id: GO_REF:0000116
  qualifier: enables
  review:
    summary: ABCA1 preferentially flops phosphatidylcholine to the outer leaflet; PC is its favored substrate and most strongly stimulates its ATPase (IDA/IMP).
    action: ACCEPT
    reason: PC is the preferred floppase substrate.
- term:
    id: GO:0090556
    label: phosphatidylserine floppase activity
  evidence_type: IEA
  original_reference_id: GO_REF:0000116
  qualifier: enables
  review:
    summary: ABCA1 also translocates phosphatidylserine to the outer leaflet, less efficiently than PC; PS floppase defect underlies the Scott-syndrome-associated variant.
    action: ACCEPT
    reason: Demonstrated PS floppase activity (IDA).
- term:
    id: GO:0099039
    label: sphingolipid translocation
  evidence_type: IEA
  original_reference_id: GO_REF:0000108
  qualifier: involved_in
  review:
    summary: ABCA1 translocates sphingomyelin/sphingolipid across the membrane, consistent with its measured sphingolipid floppase activity (IEA).
    action: ACCEPT
    reason: Sphingolipid inter-leaflet translocation.
- term:
    id: GO:0140326
    label: ATPase-coupled intramembrane lipid carrier activity
  evidence_type: IEA
  original_reference_id: GO_REF:0000120
  qualifier: enables
  review:
    summary: 'Directly measured EC 7.6.2.1 activity: ATP-coupled translocation of phospholipids across the membrane bilayer, the proximal molecular activity of ABCA1 (EXP/IDA evidence).'
    action: ACCEPT
    reason: Defining floppase MF; experimentally demonstrated.
- term:
    id: GO:0140359
    label: ABC-type transporter activity
  evidence_type: IEA
  original_reference_id: GO_REF:0000002
  qualifier: enables
  review:
    summary: ABCA1 is a member of the ABC transporter superfamily that uses ATP binding/hydrolysis to drive transmembrane lipid translocation; the family-level MF is correct and central.
    action: ACCEPT
    reason: Bona fide ABC transporter; ATP-driven lipid translocase.
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:12084722
  qualifier: enables
  review:
    summary: Generic 'protein binding' (n=9 IPI) conveys no specific function; ABCA1's informative interactions (apoA-I, syntaxin, CDC42, ABCA8) are captured by specific terms.
    action: MARK_AS_OVER_ANNOTATED
    reason: Uninformative; superseded by specific binding terms.
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:15469992
  qualifier: enables
  review:
    summary: Generic 'protein binding' (n=9 IPI) conveys no specific function; ABCA1's informative interactions (apoA-I, syntaxin, CDC42, ABCA8) are captured by specific terms.
    action: MARK_AS_OVER_ANNOTATED
    reason: Uninformative; superseded by specific binding terms.
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:16192269
  qualifier: enables
  review:
    summary: Generic 'protein binding' (n=9 IPI) conveys no specific function; ABCA1's informative interactions (apoA-I, syntaxin, CDC42, ABCA8) are captured by specific terms.
    action: MARK_AS_OVER_ANNOTATED
    reason: Uninformative; superseded by specific binding terms.
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:16443932
  qualifier: enables
  review:
    summary: Generic 'protein binding' (n=9 IPI) conveys no specific function; ABCA1's informative interactions (apoA-I, syntaxin, CDC42, ABCA8) are captured by specific terms.
    action: MARK_AS_OVER_ANNOTATED
    reason: Uninformative; superseded by specific binding terms.
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:23931754
  qualifier: enables
  review:
    summary: Generic 'protein binding' (n=9 IPI) conveys no specific function; ABCA1's informative interactions (apoA-I, syntaxin, CDC42, ABCA8) are captured by specific terms.
    action: MARK_AS_OVER_ANNOTATED
    reason: Uninformative; superseded by specific binding terms.
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:25170080
  qualifier: enables
  review:
    summary: Generic 'protein binding' (n=9 IPI) conveys no specific function; ABCA1's informative interactions (apoA-I, syntaxin, CDC42, ABCA8) are captured by specific terms.
    action: MARK_AS_OVER_ANNOTATED
    reason: Uninformative; superseded by specific binding terms.
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:30458687
  qualifier: enables
  review:
    summary: Generic 'protein binding' (n=9 IPI) conveys no specific function; ABCA1's informative interactions (apoA-I, syntaxin, CDC42, ABCA8) are captured by specific terms.
    action: MARK_AS_OVER_ANNOTATED
    reason: Uninformative; superseded by specific binding terms.
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:36115835
  qualifier: enables
  review:
    summary: Generic 'protein binding' (n=9 IPI) conveys no specific function; ABCA1's informative interactions (apoA-I, syntaxin, CDC42, ABCA8) are captured by specific terms.
    action: MARK_AS_OVER_ANNOTATED
    reason: Uninformative; superseded by specific binding terms.
- term:
    id: GO:0005794
    label: Golgi apparatus
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  qualifier: located_in
  review:
    summary: ABCA1 transits the Golgi during biosynthesis/maturation; this is a secondary biosynthetic-trafficking location, not its functional efflux site (IEA).
    action: KEEP_AS_NON_CORE
    reason: Secretory-pathway transit location.
- term:
    id: GO:0007584
    label: response to nutrient
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  qualifier: involved_in
  review:
    summary: ABCA1 expression responds to nutrient/lipid availability as part of metabolic regulation, upstream of its efflux activity (IEA).
    action: KEEP_AS_NON_CORE
    reason: Nutrient-responsive regulation of expression.
- term:
    id: GO:0008035
    label: high-density lipoprotein particle binding
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  qualifier: enables
  review:
    summary: ABCA1 interacts with HDL particles during/after lipidation; binding mature HDL is a peripheral aspect relative to its nascent-particle assembly role (IEA).
    action: KEEP_AS_NON_CORE
    reason: Peripheral to core nascent-HDL assembly.
- term:
    id: GO:0008320
    label: transmembrane protein transporter activity
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  qualifier: enables
  review:
    summary: ABCA1 does not transport proteins; the MF should be its ATP-coupled intramembrane lipid (floppase) transporter activity (IEA/ISS).
    action: MODIFY
    reason: Wrong cargo; ABCA1 is a lipid floppase.
    proposed_replacement_terms: &id001
    - id: GO:0140326
      label: ATPase-coupled intramembrane lipid transporter activity
- term:
    id: GO:0009306
    label: protein secretion
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  qualifier: involved_in
  review:
    summary: ABCA1 has been linked to secretion of certain proteins, a pleiotropic/indirect role distinct from its lipid-floppase function (IEA/IMP/ISS).
    action: KEEP_AS_NON_CORE
    reason: Pleiotropic secretion role, non-core.
- term:
    id: GO:0009410
    label: response to xenobiotic stimulus
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  qualifier: involved_in
  review:
    summary: Organism/cell-level responsiveness to xenobiotics modulates ABCA1; contextual regulation distinct from its lipid-efflux function (IEA).
    action: KEEP_AS_NON_CORE
    reason: Contextual regulation, non-core.
- term:
    id: GO:0009897
    label: external side of plasma membrane
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  qualifier: located_in
  review:
    summary: ABCA1's large extracellular domains, including the lipid tunnel/gateway, face the external leaflet where lipid is presented to apoA-I (IEA).
    action: ACCEPT
    reason: Extracellular lipid-presenting domains.
- term:
    id: GO:0009986
    label: cell surface
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  qualifier: located_in
  review:
    summary: ABCA1 is presented at the cell surface where it engages apoA-I; surface localization requires palmitoylation and is essential for function (IEA).
    action: ACCEPT
    reason: Surface presentation for apoA-I docking.
- term:
    id: GO:0010875
    label: positive regulation of cholesterol efflux
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  qualifier: involved_in
  review:
    summary: ABCA1 is the principal positive effector of apoA-I-dependent cholesterol efflux from cells; this is a direct consequence of its transporter function (IEA).
    action: ACCEPT
    reason: Positive effector of cholesterol efflux.
- term:
    id: GO:0015914
    label: phospholipid transport
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  qualifier: involved_in
  review:
    summary: ABCA1 transports phospholipid out of the cell onto apolipoproteins; phospholipid transport is a direct output of its activity (IEA).
    action: ACCEPT
    reason: Exports phospholipid onto apolipoproteins.
- term:
    id: GO:0016323
    label: basolateral plasma membrane
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  qualifier: located_in
  review:
    summary: In polarized cells ABCA1 localizes to the basolateral plasma-membrane domain consistent with directional lipid efflux (IEA).
    action: ACCEPT
    reason: Polarized PM domain for efflux.
- term:
    id: GO:0023061
    label: signal release
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  qualifier: involved_in
  review:
    summary: ABCA1 contributes to release of signaling molecules in some contexts, an accessory role downstream of/parallel to lipid efflux (IEA/IMP/ISS).
    action: KEEP_AS_NON_CORE
    reason: Accessory signaling-release role.
- term:
    id: GO:0030301
    label: cholesterol transport
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  qualifier: involved_in
  review:
    summary: ABCA1 transports cholesterol across the plasma membrane to extracellular apolipoprotein acceptors; sterol transport is part of its core activity (IEA).
    action: ACCEPT
    reason: Transports cholesterol to apoA-I.
- term:
    id: GO:0031667
    label: response to nutrient levels
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  qualifier: involved_in
  review:
    summary: ABCA1 is regulated by cellular nutrient/lipid status; a metabolic-response context rather than a core molecular role (IEA).
    action: KEEP_AS_NON_CORE
    reason: Metabolic-status regulation, non-core.
- term:
    id: GO:0033552
    label: response to vitamin B3
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  qualifier: involved_in
  review:
    summary: Niacin (vitamin B3) raises HDL partly via ABCA1; a pharmacological-response context downstream of its regulation (IEA).
    action: KEEP_AS_NON_CORE
    reason: Pharmacological niacin response, non-core.
- term:
    id: GO:0042158
    label: lipoprotein biosynthetic process
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  qualifier: involved_in
  review:
    summary: ABCA1-mediated lipidation of apoA-I is the biosynthetic step that generates nascent HDL lipoprotein particles (IEA).
    action: ACCEPT
    reason: Generates nascent HDL lipoprotein.
- term:
    id: GO:0042626
    label: ATPase-coupled transmembrane transporter activity
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  qualifier: enables
  review:
    summary: ABCA1 couples ATP hydrolysis to vectorial transmembrane movement of lipid substrates; the active-transporter MF correctly captures its primary mechanism.
    action: ACCEPT
    reason: ATP-coupled active transport of lipids.
- term:
    id: GO:0043691
    label: reverse cholesterol transport
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  qualifier: involved_in
  review:
    summary: By generating nascent HDL from peripheral-cell cholesterol, ABCA1 initiates reverse cholesterol transport that returns cholesterol to the liver (IMP).
    action: ACCEPT
    reason: Initiates the RCT pathway.
- term:
    id: GO:0071222
    label: cellular response to lipopolysaccharide
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  qualifier: involved_in
  review:
    summary: LPS induces ABCA1 expression via an LXR-independent pathway (PubMed:12032171); an inducible-response context distinct from transport (IEA).
    action: KEEP_AS_NON_CORE
    reason: LPS-inducible expression, non-core.
- term:
    id: GO:0071300
    label: cellular response to retinoic acid
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  qualifier: involved_in
  review:
    summary: ABCA1 expression responds to retinoic-acid/RXR signaling; a transcriptional-regulation context rather than its core activity (IEA).
    action: KEEP_AS_NON_CORE
    reason: Transcriptional response to retinoid.
- term:
    id: GO:0071345
    label: cellular response to cytokine stimulus
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  qualifier: involved_in
  review:
    summary: ABCA1 expression is modulated by cytokine signaling in inflammatory contexts; a transcriptional-response effect, not its transport function (IEA).
    action: KEEP_AS_NON_CORE
    reason: Inflammatory regulation of expression.
- term:
    id: GO:0071397
    label: cellular response to cholesterol
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  qualifier: involved_in
  review:
    summary: ABCA1 expression/activity responds to cellular cholesterol load (via LXR), a regulatory response upstream of, not part of, its transport mechanism (IEA).
    action: KEEP_AS_NON_CORE
    reason: Regulatory response to sterol load.
- term:
    id: GO:0071466
    label: cellular response to xenobiotic stimulus
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  qualifier: involved_in
  review:
    summary: ABCA1 levels respond to xenobiotic exposure (nuclear-receptor-mediated); a regulatory response, not its transport mechanism (IEA).
    action: KEEP_AS_NON_CORE
    reason: Regulatory response to xenobiotics.
- term:
    id: GO:0071806
    label: protein transmembrane transport
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  qualifier: involved_in
  review:
    summary: ABCA1 is a lipid floppase, not a protein transporter; this IEA/ISS-propagated term should be recast as phospholipid efflux, its actual exported cargo.
    action: MODIFY
    reason: Mis-propagated; ABCA1 effluxes phospholipid, not protein.
    proposed_replacement_terms: &id002
    - id: GO:0033700
      label: phospholipid efflux
- term:
    id: GO:0090108
    label: positive regulation of high-density lipoprotein particle assembly
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  qualifier: involved_in
  review:
    summary: ABCA1 positively drives HDL assembly by supplying lipid to apoA-I; increased ABCA1 increases nascent-HDL production (IEA/ISS).
    action: ACCEPT
    reason: Positively drives nascent-HDL formation.
- term:
    id: GO:0120014
    label: phospholipid transfer activity
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  qualifier: enables
  review:
    summary: ABCA1 mediates transfer of phospholipid to apolipoprotein acceptors, the molecular step that lipidates apoA-I into nascent HDL (IGI/IEA).
    action: ACCEPT
    reason: Phospholipid transfer onto apolipoprotein acceptors.
- term:
    id: GO:0120020
    label: cholesterol transfer activity
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  qualifier: enables
  review:
    summary: ABCA1 promotes transfer of cholesterol to apoA-I as part of HDL biogenesis; cholesterol is a translocated substrate (RHEA:39051) effluxed alongside phospholipid (IDA).
    action: ACCEPT
    reason: Cholesterol transfer onto apoA-I in HDL assembly.
- term:
    id: GO:0140115
    label: export across plasma membrane
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  qualifier: involved_in
  review:
    summary: ABCA1 exports lipid cargo across the plasma membrane to extracellular acceptors; export directionality is intrinsic to its function (IEA/ISS).
    action: ACCEPT
    reason: Plasma-membrane export of lipid cargo.
- term:
    id: GO:0120014
    label: phospholipid transfer activity
  evidence_type: IGI
  original_reference_id: PMID:28373057
  qualifier: enables
  review:
    summary: ABCA1 mediates transfer of phospholipid to apolipoprotein acceptors, the molecular step that lipidates apoA-I into nascent HDL (IGI/IEA).
    action: ACCEPT
    reason: Phospholipid transfer onto apolipoprotein acceptors.
- term:
    id: GO:0140326
    label: ATPase-coupled intramembrane lipid carrier activity
  evidence_type: IDA
  original_reference_id: PMID:28373057
  qualifier: enables
  review:
    summary: 'Directly measured EC 7.6.2.1 activity: ATP-coupled translocation of phospholipids across the membrane bilayer, the proximal molecular activity of ABCA1 (EXP/IDA evidence).'
    action: ACCEPT
    reason: Defining floppase MF; experimentally demonstrated.
- term:
    id: GO:0005886
    label: plasma membrane
  evidence_type: IDA
  original_reference_id: GO_REF:0000052
  qualifier: located_in
  review:
    summary: ABCA1 is a multi-pass plasma-membrane protein; the cell surface is where it docks apoA-I and effluxes lipid. Best-supported localization (n=17; IDA/IMP/TAS).
    action: ACCEPT
    reason: Primary site of lipid efflux.
- term:
    id: GO:0140326
    label: ATPase-coupled intramembrane lipid carrier activity
  evidence_type: EXP
  original_reference_id: PMID:24097981
  qualifier: enables
  review:
    summary: 'Directly measured EC 7.6.2.1 activity: ATP-coupled translocation of phospholipids across the membrane bilayer, the proximal molecular activity of ABCA1 (EXP/IDA evidence).'
    action: ACCEPT
    reason: Defining floppase MF; experimentally demonstrated.
- term:
    id: GO:0005886
    label: plasma membrane
  evidence_type: IMP
  original_reference_id: PMID:35974019
  qualifier: located_in
  review:
    summary: ABCA1 is a multi-pass plasma-membrane protein; the cell surface is where it docks apoA-I and effluxes lipid. Best-supported localization (n=17; IDA/IMP/TAS).
    action: ACCEPT
    reason: Primary site of lipid efflux.
- term:
    id: GO:0033344
    label: cholesterol efflux
  evidence_type: IMP
  original_reference_id: PMID:35974019
  qualifier: involved_in
  review:
    summary: ABCA1 mediates efflux of cellular cholesterol onto apoA-I, the rate-limiting step of HDL biogenesis; the most heavily supported BP for this gene (IDA/IGI/IMP, n=9).
    action: ACCEPT
    reason: Defining physiological process of ABCA1.
- term:
    id: GO:0033700
    label: phospholipid efflux
  evidence_type: IMP
  original_reference_id: PMID:35974019
  qualifier: involved_in
  review:
    summary: ABCA1 effluxes phospholipid (chiefly PC) to apolipoproteins, the proximal output of its floppase activity and required for HDL particle formation (IDA/IGI/IMP).
    action: ACCEPT
    reason: Core BP downstream of floppase activity.
- term:
    id: GO:0090554
    label: phosphatidylcholine floppase activity
  evidence_type: IMP
  original_reference_id: PMID:35974019
  qualifier: enables
  review:
    summary: ABCA1 preferentially flops phosphatidylcholine to the outer leaflet; PC is its favored substrate and most strongly stimulates its ATPase (IDA/IMP).
    action: ACCEPT
    reason: PC is the preferred floppase substrate.
- term:
    id: GO:0140115
    label: export across plasma membrane
  evidence_type: ISS
  original_reference_id: PMID:29937375
  qualifier: involved_in
  review:
    summary: ABCA1 exports lipid cargo across the plasma membrane to extracellular acceptors; export directionality is intrinsic to its function (IEA/ISS).
    action: ACCEPT
    reason: Plasma-membrane export of lipid cargo.
- term:
    id: GO:0033344
    label: cholesterol efflux
  evidence_type: IMP
  original_reference_id: PMID:25084135
  qualifier: involved_in
  review:
    summary: ABCA1 mediates efflux of cellular cholesterol onto apoA-I, the rate-limiting step of HDL biogenesis; the most heavily supported BP for this gene (IDA/IGI/IMP, n=9).
    action: ACCEPT
    reason: Defining physiological process of ABCA1.
- term:
    id: GO:0009306
    label: protein secretion
  evidence_type: IMP
  original_reference_id: PMID:11855831
  qualifier: involved_in
  review:
    summary: ABCA1 has been linked to secretion of certain proteins, a pleiotropic/indirect role distinct from its lipid-floppase function (IEA/IMP/ISS).
    action: KEEP_AS_NON_CORE
    reason: Pleiotropic secretion role, non-core.
- term:
    id: GO:0009306
    label: protein secretion
  evidence_type: ISS
  original_reference_id: PMID:29937375
  qualifier: involved_in
  review:
    summary: ABCA1 has been linked to secretion of certain proteins, a pleiotropic/indirect role distinct from its lipid-floppase function (IEA/IMP/ISS).
    action: KEEP_AS_NON_CORE
    reason: Pleiotropic secretion role, non-core.
- term:
    id: GO:0023061
    label: signal release
  evidence_type: IMP
  original_reference_id: PMID:11855831
  qualifier: involved_in
  review:
    summary: ABCA1 contributes to release of signaling molecules in some contexts, an accessory role downstream of/parallel to lipid efflux (IEA/IMP/ISS).
    action: KEEP_AS_NON_CORE
    reason: Accessory signaling-release role.
- term:
    id: GO:0005886
    label: plasma membrane
  evidence_type: IDA
  original_reference_id: PMID:28373057
  qualifier: located_in
  review:
    summary: ABCA1 is a multi-pass plasma-membrane protein; the cell surface is where it docks apoA-I and effluxes lipid. Best-supported localization (n=17; IDA/IMP/TAS).
    action: ACCEPT
    reason: Primary site of lipid efflux.
- term:
    id: GO:0033344
    label: cholesterol efflux
  evidence_type: IGI
  original_reference_id: PMID:28373057
  qualifier: involved_in
  review:
    summary: ABCA1 mediates efflux of cellular cholesterol onto apoA-I, the rate-limiting step of HDL biogenesis; the most heavily supported BP for this gene (IDA/IGI/IMP, n=9).
    action: ACCEPT
    reason: Defining physiological process of ABCA1.
- term:
    id: GO:0033700
    label: phospholipid efflux
  evidence_type: IGI
  original_reference_id: PMID:28373057
  qualifier: involved_in
  review:
    summary: ABCA1 effluxes phospholipid (chiefly PC) to apolipoproteins, the proximal output of its floppase activity and required for HDL particle formation (IDA/IGI/IMP).
    action: ACCEPT
    reason: Core BP downstream of floppase activity.
- term:
    id: GO:0097708
    label: intracellular vesicle
  evidence_type: IDA
  original_reference_id: PMID:28373057
  qualifier: located_in
  review:
    summary: ABCA1 resides in intracellular vesicular compartments during its trafficking/recycling between PM and endosomes (IDA).
    action: ACCEPT
    reason: Trafficking/recycling vesicle pool.
- term:
    id: GO:0005886
    label: plasma membrane
  evidence_type: IDA
  original_reference_id: PMID:19556522
  qualifier: located_in
  review:
    summary: ABCA1 is a multi-pass plasma-membrane protein; the cell surface is where it docks apoA-I and effluxes lipid. Best-supported localization (n=17; IDA/IMP/TAS).
    action: ACCEPT
    reason: Primary site of lipid efflux.
- term:
    id: GO:0033344
    label: cholesterol efflux
  evidence_type: IMP
  original_reference_id: PMID:19556522
  qualifier: involved_in
  review:
    summary: ABCA1 mediates efflux of cellular cholesterol onto apoA-I, the rate-limiting step of HDL biogenesis; the most heavily supported BP for this gene (IDA/IGI/IMP, n=9).
    action: ACCEPT
    reason: Defining physiological process of ABCA1.
- term:
    id: GO:0033700
    label: phospholipid efflux
  evidence_type: IMP
  original_reference_id: PMID:19556522
  qualifier: involved_in
  review:
    summary: ABCA1 effluxes phospholipid (chiefly PC) to apolipoproteins, the proximal output of its floppase activity and required for HDL particle formation (IDA/IGI/IMP).
    action: ACCEPT
    reason: Core BP downstream of floppase activity.
- term:
    id: GO:0008320
    label: transmembrane protein transporter activity
  evidence_type: ISS
  original_reference_id: PMID:29937375
  qualifier: enables
  review:
    summary: ABCA1 does not transport proteins; the MF should be its ATP-coupled intramembrane lipid (floppase) transporter activity (IEA/ISS).
    action: MODIFY
    reason: Wrong cargo; ABCA1 is a lipid floppase.
    proposed_replacement_terms: *id001
- term:
    id: GO:0023061
    label: signal release
  evidence_type: ISS
  original_reference_id: PMID:29937375
  qualifier: involved_in
  review:
    summary: ABCA1 contributes to release of signaling molecules in some contexts, an accessory role downstream of/parallel to lipid efflux (IEA/IMP/ISS).
    action: KEEP_AS_NON_CORE
    reason: Accessory signaling-release role.
- term:
    id: GO:0071806
    label: protein transmembrane transport
  evidence_type: ISS
  original_reference_id: PMID:29937375
  qualifier: involved_in
  review:
    summary: ABCA1 is a lipid floppase, not a protein transporter; this IEA/ISS-propagated term should be recast as phospholipid efflux, its actual exported cargo.
    action: MODIFY
    reason: Mis-propagated; ABCA1 effluxes phospholipid, not protein.
    proposed_replacement_terms: *id002
- term:
    id: GO:0034616
    label: response to laminar fluid shear stress
  evidence_type: IDA
  original_reference_id: PMID:15358760
  qualifier: involved_in
  review:
    summary: Endothelial ABCA1 expression/activity responds to laminar shear stress, a vascular-context regulatory response distinct from core efflux (IDA).
    action: KEEP_AS_NON_CORE
    reason: Shear-stress regulation in vasculature.
- term:
    id: GO:0071404
    label: cellular response to low-density lipoprotein particle stimulus
  evidence_type: NAS
  original_reference_id: PMID:15358760
  qualifier: involved_in
  review:
    summary: ABCA1 responds to LDL-derived cholesterol loading by upregulation; a regulatory response context rather than its core efflux activity (NAS).
    action: KEEP_AS_NON_CORE
    reason: Regulatory response to LDL loading.
- term:
    id: GO:0046623
    label: sphingolipid floppase activity
  evidence_type: IDA
  original_reference_id: PMID:24097981
  qualifier: enables
  review:
    summary: ABCA1 can translocate sphingomyelin/sphingolipid across the membrane; sphingomyelin is among its measured catalytic substrates (IDA).
    action: ACCEPT
    reason: Sphingolipid among catalytic floppase substrates.
- term:
    id: GO:0090554
    label: phosphatidylcholine floppase activity
  evidence_type: IDA
  original_reference_id: PMID:24097981
  qualifier: enables
  review:
    summary: ABCA1 preferentially flops phosphatidylcholine to the outer leaflet; PC is its favored substrate and most strongly stimulates its ATPase (IDA/IMP).
    action: ACCEPT
    reason: PC is the preferred floppase substrate.
- term:
    id: GO:0090556
    label: phosphatidylserine floppase activity
  evidence_type: IDA
  original_reference_id: PMID:24097981
  qualifier: enables
  review:
    summary: ABCA1 also translocates phosphatidylserine to the outer leaflet, less efficiently than PC; PS floppase defect underlies the Scott-syndrome-associated variant.
    action: ACCEPT
    reason: Demonstrated PS floppase activity (IDA).
- term:
    id: GO:0033344
    label: cholesterol efflux
  evidence_type: IDA
  original_reference_id: PMID:16702602
  qualifier: involved_in
  review:
    summary: ABCA1 mediates efflux of cellular cholesterol onto apoA-I, the rate-limiting step of HDL biogenesis; the most heavily supported BP for this gene (IDA/IGI/IMP, n=9).
    action: ACCEPT
    reason: Defining physiological process of ABCA1.
- term:
    id: GO:0090554
    label: phosphatidylcholine floppase activity
  evidence_type: IDA
  original_reference_id: PMID:16702602
  qualifier: enables
  review:
    summary: ABCA1 preferentially flops phosphatidylcholine to the outer leaflet; PC is its favored substrate and most strongly stimulates its ATPase (IDA/IMP).
    action: ACCEPT
    reason: PC is the preferred floppase substrate.
- term:
    id: GO:0140328
    label: floppase activity
  evidence_type: IDA
  original_reference_id: PMID:16702602
  qualifier: enables
  review:
    summary: ABCA1 acts as a floppase, moving phospholipids from the cytoplasmic to the exoplasmic leaflet of the plasma membrane prior to transfer onto apoA-I (IDA).
    action: ACCEPT
    reason: Floppase mechanism is the core transport mode.
- term:
    id: GO:0031210
    label: phosphatidylcholine binding
  evidence_type: IDA
  original_reference_id: PMID:24097981
  qualifier: enables
  review:
    summary: ABCA1 binds phosphatidylcholine, its preferred transport substrate that engages the extracellular tunnel/gateway domain during translocation (IDA).
    action: ACCEPT
    reason: Substrate binding for the preferred PC cargo.
- term:
    id: GO:0140328
    label: floppase activity
  evidence_type: IDA
  original_reference_id: PMID:24097981
  qualifier: enables
  review:
    summary: ABCA1 acts as a floppase, moving phospholipids from the cytoplasmic to the exoplasmic leaflet of the plasma membrane prior to transfer onto apoA-I (IDA).
    action: ACCEPT
    reason: Floppase mechanism is the core transport mode.
- term:
    id: GO:0090108
    label: positive regulation of high-density lipoprotein particle assembly
  evidence_type: ISS
  original_reference_id: GO_REF:0000024
  qualifier: involved_in
  review:
    summary: ABCA1 positively drives HDL assembly by supplying lipid to apoA-I; increased ABCA1 increases nascent-HDL production (IEA/ISS).
    action: ACCEPT
    reason: Positively drives nascent-HDL formation.
- term:
    id: GO:0005768
    label: endosome
  evidence_type: IDA
  original_reference_id: PMID:24097981
  qualifier: located_in
  review:
    summary: ABCA1 cycles through the endosomal system between the cell surface and intracellular pools; endosomal localization is documented (IDA/IEA).
    action: ACCEPT
    reason: Part of ABCA1's recycling itinerary.
- term:
    id: GO:0005886
    label: plasma membrane
  evidence_type: IDA
  original_reference_id: PMID:24097981
  qualifier: located_in
  review:
    summary: ABCA1 is a multi-pass plasma-membrane protein; the cell surface is where it docks apoA-I and effluxes lipid. Best-supported localization (n=17; IDA/IMP/TAS).
    action: ACCEPT
    reason: Primary site of lipid efflux.
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:14754908
  qualifier: enables
  review:
    summary: Generic 'protein binding' (n=9 IPI) conveys no specific function; ABCA1's informative interactions (apoA-I, syntaxin, CDC42, ABCA8) are captured by specific terms.
    action: MARK_AS_OVER_ANNOTATED
    reason: Uninformative; superseded by specific binding terms.
- term:
    id: GO:0034380
    label: high-density lipoprotein particle assembly
  evidence_type: IMP
  original_reference_id: PMID:14754908
  qualifier: involved_in
  review:
    summary: ABCA1-driven lipidation of apoA-I assembles nascent (pre-beta) HDL particles; loss of ABCA1 abolishes HDL, defining its role in particle assembly (IMP).
    action: ACCEPT
    reason: Builds nascent HDL particles.
- term:
    id: GO:0007186
    label: G protein-coupled receptor signaling pathway
  evidence_type: IMP
  original_reference_id: PMID:16443932
  qualifier: involved_in
  review:
    summary: ABCA1 modulates downstream signaling (e.g. via apoA-I engagement and Cdc42), but GPCR signaling is a secondary, indirect consequence of its lipid-transport role (IMP).
    action: KEEP_AS_NON_CORE
    reason: Indirect signaling effect, not core transport.
- term:
    id: GO:0007189
    label: adenylate cyclase-activating G protein-coupled receptor signaling pathway
  evidence_type: IMP
  original_reference_id: PMID:14701824
  qualifier: involved_in
  review:
    summary: Reported adenylate-cyclase-coupled signaling is a downstream consequence of ABCA1/apoA-I interaction rather than its primary lipid-efflux activity (IMP).
    action: KEEP_AS_NON_CORE
    reason: Downstream signaling, secondary to efflux.
- term:
    id: GO:0045121
    label: membrane raft
  evidence_type: IDA
  original_reference_id: PMID:15469992
  qualifier: located_in
  review:
    summary: ABCA1 associates with/remodels membrane-raft lipid microdomains during efflux; raft localization is a contextual feature of its PM activity (IDA).
    action: KEEP_AS_NON_CORE
    reason: Lipid-microdomain context of efflux.
- term:
    id: GO:0045332
    label: phospholipid translocation
  evidence_type: IDA
  original_reference_id: PMID:24097981
  qualifier: involved_in
  review:
    summary: ABCA1 translocates phospholipids between membrane leaflets, the molecular event underlying its floppase/efflux function (IDA/IEA).
    action: ACCEPT
    reason: Inter-leaflet phospholipid translocation.
- term:
    id: GO:0042632
    label: cholesterol homeostasis
  evidence_type: TAS
  original_reference_id: PMID:24097981
  qualifier: involved_in
  review:
    summary: ABCA1 is a central regulator of cellular cholesterol balance, removing excess free cholesterol via efflux; defects cause massive tissue cholesteryl-ester deposition (IDA/TAS).
    action: ACCEPT
    reason: Removes excess cellular cholesterol.
- term:
    id: GO:0090107
    label: regulation of high-density lipoprotein particle assembly
  evidence_type: TAS
  original_reference_id: PMID:24097981
  qualifier: involved_in
  review:
    summary: ABCA1 activity sets the rate of HDL particle assembly; its expression/activity is the principal control point for nascent-HDL formation (TAS).
    action: ACCEPT
    reason: Rate-limiting regulator of HDL assembly.
- term:
    id: GO:0005886
    label: plasma membrane
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-5682111
  qualifier: located_in
  review:
    summary: ABCA1 is a multi-pass plasma-membrane protein; the cell surface is where it docks apoA-I and effluxes lipid. Best-supported localization (n=17; IDA/IMP/TAS).
    action: ACCEPT
    reason: Primary site of lipid efflux.
- term:
    id: GO:0005789
    label: endoplasmic reticulum membrane
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-5682084
  qualifier: located_in
  review:
    summary: ABCA1 is synthesized and folded in the ER membrane before trafficking to the cell surface; ER residence is biosynthetic, not its active site (TAS).
    action: KEEP_AS_NON_CORE
    reason: Biosynthetic ER stage, not functional site.
- term:
    id: GO:0005789
    label: endoplasmic reticulum membrane
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-5682103
  qualifier: located_in
  review:
    summary: ABCA1 is synthesized and folded in the ER membrane before trafficking to the cell surface; ER residence is biosynthetic, not its active site (TAS).
    action: KEEP_AS_NON_CORE
    reason: Biosynthetic ER stage, not functional site.
- term:
    id: GO:0005886
    label: plasma membrane
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-216723
  qualifier: located_in
  review:
    summary: ABCA1 is a multi-pass plasma-membrane protein; the cell surface is where it docks apoA-I and effluxes lipid. Best-supported localization (n=17; IDA/IMP/TAS).
    action: ACCEPT
    reason: Primary site of lipid efflux.
- term:
    id: GO:0005886
    label: plasma membrane
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-216727
  qualifier: located_in
  review:
    summary: ABCA1 is a multi-pass plasma-membrane protein; the cell surface is where it docks apoA-I and effluxes lipid. Best-supported localization (n=17; IDA/IMP/TAS).
    action: ACCEPT
    reason: Primary site of lipid efflux.
- term:
    id: GO:0005886
    label: plasma membrane
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-216757
  qualifier: located_in
  review:
    summary: ABCA1 is a multi-pass plasma-membrane protein; the cell surface is where it docks apoA-I and effluxes lipid. Best-supported localization (n=17; IDA/IMP/TAS).
    action: ACCEPT
    reason: Primary site of lipid efflux.
- term:
    id: GO:0005886
    label: plasma membrane
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-5682101
  qualifier: located_in
  review:
    summary: ABCA1 is a multi-pass plasma-membrane protein; the cell surface is where it docks apoA-I and effluxes lipid. Best-supported localization (n=17; IDA/IMP/TAS).
    action: ACCEPT
    reason: Primary site of lipid efflux.
- term:
    id: GO:0005886
    label: plasma membrane
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-5682103
  qualifier: located_in
  review:
    summary: ABCA1 is a multi-pass plasma-membrane protein; the cell surface is where it docks apoA-I and effluxes lipid. Best-supported localization (n=17; IDA/IMP/TAS).
    action: ACCEPT
    reason: Primary site of lipid efflux.
- term:
    id: GO:0051117
    label: ATPase binding
  evidence_type: IPI
  original_reference_id: PMID:23931754
  qualifier: enables
  review:
    summary: Binding to another ATPase is too generic to describe ABCA1's molecular role and adds nothing beyond its specific partner interactions (IPI).
    action: MARK_AS_OVER_ANNOTATED
    reason: Generic enzyme-binding; uninformative.
- term:
    id: GO:0005102
    label: signaling receptor binding
  evidence_type: IPI
  original_reference_id: PMID:23931754
  qualifier: enables
  review:
    summary: Generic signaling-receptor binding does not specify a functional partnership; ABCA1's lipid-efflux role is not informatively captured by this term (IPI).
    action: MARK_AS_OVER_ANNOTATED
    reason: Uninformative generic binding term.
- term:
    id: GO:0005886
    label: plasma membrane
  evidence_type: IDA
  original_reference_id: PMID:23931754
  qualifier: located_in
  review:
    summary: ABCA1 is a multi-pass plasma-membrane protein; the cell surface is where it docks apoA-I and effluxes lipid. Best-supported localization (n=17; IDA/IMP/TAS).
    action: ACCEPT
    reason: Primary site of lipid efflux.
- term:
    id: GO:0033344
    label: cholesterol efflux
  evidence_type: IDA
  original_reference_id: PMID:23931754
  qualifier: involved_in
  review:
    summary: ABCA1 mediates efflux of cellular cholesterol onto apoA-I, the rate-limiting step of HDL biogenesis; the most heavily supported BP for this gene (IDA/IGI/IMP, n=9).
    action: ACCEPT
    reason: Defining physiological process of ABCA1.
- term:
    id: GO:0048471
    label: perinuclear region of cytoplasm
  evidence_type: IDA
  original_reference_id: PMID:23931754
  qualifier: located_in
  review:
    summary: ABCA1 is detected in the perinuclear region reflecting its biosynthetic/recycling intracellular pool rather than its functional surface location (IDA).
    action: KEEP_AS_NON_CORE
    reason: Intracellular biosynthetic/recycling pool.
- term:
    id: GO:0005886
    label: plasma membrane
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-1989765
  qualifier: located_in
  review:
    summary: ABCA1 is a multi-pass plasma-membrane protein; the cell surface is where it docks apoA-I and effluxes lipid. Best-supported localization (n=17; IDA/IMP/TAS).
    action: ACCEPT
    reason: Primary site of lipid efflux.
- term:
    id: GO:0005886
    label: plasma membrane
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-9618479
  qualifier: located_in
  review:
    summary: ABCA1 is a multi-pass plasma-membrane protein; the cell surface is where it docks apoA-I and effluxes lipid. Best-supported localization (n=17; IDA/IMP/TAS).
    action: ACCEPT
    reason: Primary site of lipid efflux.
- term:
    id: GO:0005886
    label: plasma membrane
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-9619756
  qualifier: located_in
  review:
    summary: ABCA1 is a multi-pass plasma-membrane protein; the cell surface is where it docks apoA-I and effluxes lipid. Best-supported localization (n=17; IDA/IMP/TAS).
    action: ACCEPT
    reason: Primary site of lipid efflux.
- term:
    id: GO:0032489
    label: regulation of Cdc42 protein signal transduction
  evidence_type: IMP
  original_reference_id: PMID:16443932
  qualifier: involved_in
  review:
    summary: ABCA1/apoA-I engagement regulates Cdc42 GTPase signaling affecting cytoskeleton/membrane dynamics; a downstream signaling output of efflux (IMP).
    action: KEEP_AS_NON_CORE
    reason: Downstream Cdc42 signaling from apoA-I engagement.
- term:
    id: GO:0019905
    label: syntaxin binding
  evidence_type: IPI
  original_reference_id: PMID:15469992
  qualifier: enables
  review:
    summary: ABCA1 binds syntaxin-12 (STX12), implicating SNARE-mediated trafficking in its recycling; a specific trafficking interaction, not core MF (IPI).
    action: KEEP_AS_NON_CORE
    reason: STX12 interaction supports trafficking.
- term:
    id: GO:0010745
    label: negative regulation of macrophage derived foam cell differentiation
  evidence_type: TAS
  original_reference_id: PMID:18490524
  qualifier: involved_in
  review:
    summary: By effluxing cholesterol from macrophages, ABCA1 prevents foam-cell formation; an important but downstream physiological consequence of efflux (TAS).
    action: KEEP_AS_NON_CORE
    reason: Downstream of macrophage cholesterol efflux.
- term:
    id: GO:0010887
    label: negative regulation of cholesterol storage
  evidence_type: TAS
  original_reference_id: PMID:18490524
  qualifier: involved_in
  review:
    summary: By effluxing cholesterol, ABCA1 limits intracellular cholesteryl-ester accumulation; ABCA1 loss leads to cholesterol-ester storage (Tangier) (TAS).
    action: ACCEPT
    reason: Efflux limits intracellular cholesterol storage.
- term:
    id: GO:0034380
    label: high-density lipoprotein particle assembly
  evidence_type: IMP
  original_reference_id: PMID:10431236
  qualifier: involved_in
  review:
    summary: ABCA1-driven lipidation of apoA-I assembles nascent (pre-beta) HDL particles; loss of ABCA1 abolishes HDL, defining its role in particle assembly (IMP).
    action: ACCEPT
    reason: Builds nascent HDL particles.
- term:
    id: GO:0034380
    label: high-density lipoprotein particle assembly
  evidence_type: IMP
  original_reference_id: PMID:17305370
  qualifier: involved_in
  review:
    summary: ABCA1-driven lipidation of apoA-I assembles nascent (pre-beta) HDL particles; loss of ABCA1 abolishes HDL, defining its role in particle assembly (IMP).
    action: ACCEPT
    reason: Builds nascent HDL particles.
- term:
    id: GO:0034185
    label: apolipoprotein binding
  evidence_type: IPI
  original_reference_id: PMID:11162594
  qualifier: enables
  review:
    summary: ABCA1 binds apolipoprotein acceptors (apoA-I, and functionally apoE) to lipidate them; apolipoprotein binding is integral to HDL biogenesis (IPI).
    action: ACCEPT
    reason: Binds apolipoprotein acceptors for lipidation.
- term:
    id: GO:0034186
    label: apolipoprotein A-I binding
  evidence_type: IPI
  original_reference_id: PMID:11162594
  qualifier: enables
  review:
    summary: ABCA1 binds lipid-poor apoA-I, the obligate acceptor onto which it loads phospholipid and cholesterol; this interaction is essential for nascent-HDL formation (IPI).
    action: ACCEPT
    reason: ApoA-I is the lipid acceptor; binding is mechanistically core.
- term:
    id: GO:0034186
    label: apolipoprotein A-I binding
  evidence_type: IPI
  original_reference_id: PMID:16443932
  qualifier: enables
  review:
    summary: ABCA1 binds lipid-poor apoA-I, the obligate acceptor onto which it loads phospholipid and cholesterol; this interaction is essential for nascent-HDL formation (IPI).
    action: ACCEPT
    reason: ApoA-I is the lipid acceptor; binding is mechanistically core.
- term:
    id: GO:0034188
    label: apolipoprotein A-I receptor activity
  evidence_type: IDA
  original_reference_id: PMID:16443932
  qualifier: enables
  review:
    summary: ABCA1 functions as the cell-surface receptor for apoA-I, docking the acceptor to enable directed lipid efflux (IDA).
    action: ACCEPT
    reason: Receptor for the apoA-I lipid acceptor.
- term:
    id: GO:0033344
    label: cholesterol efflux
  evidence_type: IDA
  original_reference_id: PMID:11162594
  qualifier: involved_in
  review:
    summary: ABCA1 mediates efflux of cellular cholesterol onto apoA-I, the rate-limiting step of HDL biogenesis; the most heavily supported BP for this gene (IDA/IGI/IMP, n=9).
    action: ACCEPT
    reason: Defining physiological process of ABCA1.
- term:
    id: GO:0033700
    label: phospholipid efflux
  evidence_type: IDA
  original_reference_id: PMID:11162594
  qualifier: involved_in
  review:
    summary: ABCA1 effluxes phospholipid (chiefly PC) to apolipoproteins, the proximal output of its floppase activity and required for HDL particle formation (IDA/IGI/IMP).
    action: ACCEPT
    reason: Core BP downstream of floppase activity.
- term:
    id: GO:0031267
    label: small GTPase binding
  evidence_type: IPI
  original_reference_id: PMID:16443932
  qualifier: enables
  review:
    summary: ABCA1 binds CDC42 (a small GTPase), linking efflux to cytoskeletal signaling; a specific partner interaction peripheral to transport (IPI).
    action: KEEP_AS_NON_CORE
    reason: CDC42 interaction; peripheral signaling link.
- term:
    id: GO:0033344
    label: cholesterol efflux
  evidence_type: IMP
  original_reference_id: PMID:16443932
  qualifier: involved_in
  review:
    summary: ABCA1 mediates efflux of cellular cholesterol onto apoA-I, the rate-limiting step of HDL biogenesis; the most heavily supported BP for this gene (IDA/IGI/IMP, n=9).
    action: ACCEPT
    reason: Defining physiological process of ABCA1.
- term:
    id: GO:0042632
    label: cholesterol homeostasis
  evidence_type: IDA
  original_reference_id: PMID:10431236
  qualifier: involved_in
  review:
    summary: ABCA1 is a central regulator of cellular cholesterol balance, removing excess free cholesterol via efflux; defects cause massive tissue cholesteryl-ester deposition (IDA/TAS).
    action: ACCEPT
    reason: Removes excess cellular cholesterol.
- term:
    id: GO:0033700
    label: phospholipid efflux
  evidence_type: IMP
  original_reference_id: PMID:16702602
  qualifier: involved_in
  review:
    summary: ABCA1 effluxes phospholipid (chiefly PC) to apolipoproteins, the proximal output of its floppase activity and required for HDL particle formation (IDA/IGI/IMP).
    action: ACCEPT
    reason: Core BP downstream of floppase activity.
- term:
    id: GO:0055091
    label: phospholipid homeostasis
  evidence_type: IMP
  original_reference_id: PMID:16702602
  qualifier: involved_in
  review:
    summary: By exporting membrane phospholipids to apolipoproteins, ABCA1 helps maintain cellular phospholipid balance (IMP).
    action: ACCEPT
    reason: Maintains cellular phospholipid balance via efflux.
- term:
    id: GO:0015485
    label: cholesterol binding
  evidence_type: IC
  original_reference_id: PMID:12084722
  qualifier: enables
  review:
    summary: ABCA1 binds cholesterol, a substrate it exports; cholesterol also feedback-inhibits its ATPase activity (IC).
    action: ACCEPT
    reason: Cholesterol is a bound transport substrate.
- term:
    id: GO:0033700
    label: phospholipid efflux
  evidence_type: IDA
  original_reference_id: PMID:10431236
  qualifier: involved_in
  review:
    summary: ABCA1 effluxes phospholipid (chiefly PC) to apolipoproteins, the proximal output of its floppase activity and required for HDL particle formation (IDA/IGI/IMP).
    action: ACCEPT
    reason: Core BP downstream of floppase activity.
- term:
    id: GO:0005524
    label: ATP binding
  evidence_type: IDA
  original_reference_id: PMID:11700048
  qualifier: enables
  review:
    summary: ABCA1 has two nucleotide-binding cassettes that bind ATP; nucleotide binding/hydrolysis powers the conformational cycle driving lipid floppase activity (IDA-supported).
    action: ACCEPT
    reason: Two ABC/NBD domains; ATP binding is required for transport.
- term:
    id: GO:0005886
    label: plasma membrane
  evidence_type: IDA
  original_reference_id: PMID:10525055
  qualifier: located_in
  review:
    summary: ABCA1 is a multi-pass plasma-membrane protein; the cell surface is where it docks apoA-I and effluxes lipid. Best-supported localization (n=17; IDA/IMP/TAS).
    action: ACCEPT
    reason: Primary site of lipid efflux.
- term:
    id: GO:0007040
    label: lysosome organization
  evidence_type: IDA
  original_reference_id: PMID:15163665
  qualifier: involved_in
  review:
    summary: ABCA1 influences lysosome organization linked to cellular lipid handling, a downstream cellular consequence rather than its transport function (IDA).
    action: KEEP_AS_NON_CORE
    reason: Downstream lipid-handling effect.
- term:
    id: GO:0008203
    label: cholesterol metabolic process
  evidence_type: IDA
  original_reference_id: PMID:14747463
  qualifier: involved_in
  review:
    summary: ABCA1 participates in cholesterol metabolism by exporting cellular cholesterol, shaping intracellular sterol pools (IDA).
    action: ACCEPT
    reason: Cholesterol export shapes sterol metabolism.
- term:
    id: GO:0016197
    label: endosomal transport
  evidence_type: IDA
  original_reference_id: PMID:14747463
  qualifier: involved_in
  review:
    summary: ABCA1's endosomal recycling supports surface availability, a trafficking process supporting but distinct from its core efflux activity (IDA).
    action: KEEP_AS_NON_CORE
    reason: Supports surface recycling of ABCA1.
- term:
    id: GO:0030139
    label: endocytic vesicle
  evidence_type: IDA
  original_reference_id: PMID:14747463
  qualifier: located_in
  review:
    summary: ABCA1 is found in endocytic vesicles as it recycles between the plasma membrane and endosomes (IDA).
    action: ACCEPT
    reason: Recycling endocytic compartment.
- term:
    id: GO:0032367
    label: intracellular cholesterol transport
  evidence_type: IMP
  original_reference_id: PMID:10431236
  qualifier: involved_in
  review:
    summary: ABCA1 contributes to mobilization/trafficking of intracellular cholesterol toward the plasma membrane for efflux (IMP).
    action: ACCEPT
    reason: Mobilizes intracellular cholesterol for efflux.
- term:
    id: GO:0033344
    label: cholesterol efflux
  evidence_type: IDA
  original_reference_id: PMID:10431236
  qualifier: involved_in
  review:
    summary: ABCA1 mediates efflux of cellular cholesterol onto apoA-I, the rate-limiting step of HDL biogenesis; the most heavily supported BP for this gene (IDA/IGI/IMP, n=9).
    action: ACCEPT
    reason: Defining physiological process of ABCA1.
- term:
    id: GO:0043691
    label: reverse cholesterol transport
  evidence_type: IMP
  original_reference_id: PMID:10431236
  qualifier: involved_in
  review:
    summary: By generating nascent HDL from peripheral-cell cholesterol, ABCA1 initiates reverse cholesterol transport that returns cholesterol to the liver (IMP).
    action: ACCEPT
    reason: Initiates the RCT pathway.
- term:
    id: GO:0045335
    label: phagocytic vesicle
  evidence_type: IDA
  original_reference_id: PMID:15469992
  qualifier: located_in
  review:
    summary: ABCA1 on phagocytic vesicles relates to its accessory role in apoptotic-cell engulfment, downstream of/parallel to lipid efflux (IDA).
    action: KEEP_AS_NON_CORE
    reason: Engulfment-related localization, non-core.
- term:
    id: GO:0060155
    label: platelet dense granule organization
  evidence_type: IMP
  original_reference_id: PMID:15163665
  qualifier: involved_in
  review:
    summary: ABCA1 affects platelet dense-granule organization, a tissue-specific pleiotropic role separate from its central lipid-efflux function (IMP).
    action: KEEP_AS_NON_CORE
    reason: Pleiotropic platelet role, non-core.
- term:
    id: GO:0120020
    label: cholesterol transfer activity
  evidence_type: IDA
  original_reference_id: PMID:12084722
  qualifier: enables
  review:
    summary: ABCA1 promotes transfer of cholesterol to apoA-I as part of HDL biogenesis; cholesterol is a translocated substrate (RHEA:39051) effluxed alongside phospholipid (IDA).
    action: ACCEPT
    reason: Cholesterol transfer onto apoA-I in HDL assembly.
references:
- id: GO_REF:0000002
  title: Gene Ontology annotation through association of InterPro records with GO terms
  findings: []
- id: GO_REF:0000024
  title: Manual transfer of experimentally-verified manual GO annotation data to orthologs by curator judgment of sequence similarity
  findings: []
- id: GO_REF:0000033
  title: Annotation inferences using phylogenetic trees
  findings: []
- id: GO_REF:0000044
  title: Gene Ontology annotation based on UniProtKB/Swiss-Prot Subcellular Location vocabulary mapping, accompanied by conservative changes to GO terms applied by UniProt
  findings: []
- id: GO_REF:0000052
  title: Gene Ontology annotation based on curation of immunofluorescence data
  findings: []
- id: GO_REF:0000107
  title: Automatic transfer of experimentally verified manual GO annotation data to orthologs using Ensembl Compara
  findings: []
- id: GO_REF:0000108
  title: Automatic assignment of GO terms using logical inference, based on on inter-ontology links
  findings: []
- id: GO_REF:0000116
  title: Automatic Gene Ontology annotation based on Rhea mapping
  findings: []
- id: GO_REF:0000117
  title: Electronic Gene Ontology annotations created by ARBA machine learning models
  findings: []
- id: GO_REF:0000120
  title: Combined Automated Annotation using Multiple IEA Methods
  findings: []
- id: PMID:10431236
  title: Mutations in ABC1 in Tangier disease and familial high-density lipoprotein deficiency.
  findings: []
- id: PMID:10525055
  title: The Tangier disease gene product ABC1 controls the cellular apolipoprotein-mediated lipid removal pathway.
  findings: []
- id: PMID:11162594
  title: Apolipoprotein specificity for lipid efflux by the human ABCAI transporter.
  findings: []
- id: PMID:11700048
  title: 'Characterization of the ATPase cycle of human ABCA1: implications for its function as a regulator rather than an active transporter.'
  findings: []
- id: PMID:11855831
  title: The ATP binding cassette transporter A1 contributes to the secretion of interleukin 1beta from macrophages but not from monocytes.
  findings: []
- id: PMID:12084722
  title: Naturally occurring mutations in the largest extracellular loops of ABCA1 can disrupt its direct interaction with apolipoprotein A-I.
  findings: []
- id: PMID:14701824
  title: Apolipoprotein A-I activates cellular cAMP signaling through the ABCA1 transporter.
  findings: []
- id: PMID:14747463
  title: 'The ABCA1 transporter modulates late endocytic trafficking: insights from the correction of the genetic defect in Tangier disease.'
  findings: []
- id: PMID:14754908
  title: 'Molecular interactions between apoE and ABCA1: impact on apoE lipidation.'
  findings: []
- id: PMID:15163665
  title: Impaired platelet activation in familial high density lipoprotein deficiency (Tangier disease).
  findings: []
- id: PMID:15358760
  title: 'Sterol-responsive element-binding protein (SREBP) 2 down-regulates ATP-binding cassette transporter A1 in vascular endothelial cells: a novel role of SREBP in regulating cholesterol metabolism.'
  findings: []
- id: PMID:15469992
  title: Association of ABCA1 with syntaxin 13 and flotillin-1 and enhanced phagocytosis in tangier cells.
  findings: []
- id: PMID:16192269
  title: Purification of ATP-binding cassette transporter A1 and associated binding proteins reveals the importance of beta1-syntrophin in cholesterol efflux.
  findings: []
- id: PMID:16443932
  title: Apolipoprotein A-I activates Cdc42 signaling through the ABCA1 transporter.
  findings: []
- id: PMID:16702602
  title: Efflux of sphingomyelin, cholesterol, and phosphatidylcholine by ABCG1.
  findings: []
- id: PMID:17305370
  title: The C-terminal lipid-binding domain of apolipoprotein E is a highly efficient mediator of ABCA1-dependent cholesterol efflux that promotes the assembly of high-density lipoproteins.
  findings: []
- id: PMID:18490524
  title: Reduced expression of ATP-binding cassette transporter G1 increases cholesterol accumulation in macrophages of patients with type 2 diabetes mellitus.
  findings: []
- id: PMID:19556522
  title: Palmitoylation of ATP-binding cassette transporter A1 is essential for its trafficking and function.
  findings: []
- id: PMID:23931754
  title: ABCA12 regulates ABCA1-dependent cholesterol efflux from macrophages and the development of atherosclerosis.
  findings: []
- id: PMID:24097981
  title: Differential phospholipid substrates and directional transport by ATP-binding cassette proteins ABCA1, ABCA7, and ABCA4 and disease-causing mutants.
  findings: []
- id: PMID:25084135
  title: MicroRNA-19b promotes macrophage cholesterol accumulation and aortic atherosclerosis by targeting ATP-binding cassette transporter A1.
  findings: []
- id: PMID:25170080
  title: HIV-1 protein Nef inhibits activity of ATP-binding cassette transporter A1 by targeting endoplasmic reticulum chaperone calnexin.
  findings: []
- id: PMID:28373057
  title: Lysophosphatidylcholine export by human ABCA7.
  findings: []
- id: PMID:29937375
  title: Chlamydia pneumoniae Hijacks a Host Autoregulatory IL-1β Loop to Drive Foam Cell Formation and Accelerate Atherosclerosis.
  findings: []
- id: PMID:30458687
  title: Apolipoprotein A-I directly interacts with extracellular domain 1 of human ABCA1.
  findings: []
- id: PMID:35974019
  title: ABCA1 is an extracellular phospholipid translocase.
  findings: []
- id: PMID:36115835
  title: Quantitative fragmentomics allow affinity mapping of interactomes.
  findings: []
- id: Reactome:R-HSA-1989765
  title: Expression of ABCA1
  findings: []
- id: Reactome:R-HSA-216723
  title: 4xPALM-C-p-2S-ABCA1 tetramer transports CHOL from transport vesicle membrane to plasma membrane
  findings: []
- id: Reactome:R-HSA-216727
  title: 4xPALM-C-p-2S-ABCA1 tetramer binds APOA1
  findings: []
- id: Reactome:R-HSA-216757
  title: 4xPALM-C-p-2S-ABCA1 tetramer transports PL from transport vesicle membrane to plasma membrane
  findings: []
- id: Reactome:R-HSA-5682084
  title: ZDHCC8 transfers PALM from PALM-CoA to ABCA1 tetramer
  findings: []
- id: Reactome:R-HSA-5682101
  title: PKA phosphorylates 4xPALM-C-p-2S-ABCA1 tetramer
  findings: []
- id: Reactome:R-HSA-5682103
  title: 4xPALM-C-ABCA1 tetramer translocates from ER membrane to plasma membrane
  findings: []
- id: Reactome:R-HSA-5682111
  title: Defective ABCA1 does not transport CHOL from transport vesicle membrane to plasma membrane
  findings: []
- id: Reactome:R-HSA-9618479
  title: ABCA1 mRNA is translated
  findings: []
- id: Reactome:R-HSA-9619756
  title: NR1H2 binds ABCA1
  findings: []
- id: file:human/ABCA1/ABCA1-uniprot.txt
  title: UniProt text export for ABCA1 (O95477)
  findings: []
  reference_review:
    relevance: HIGH
    correctness: VERIFIED
    review_notes: Local UniProt record directly supports ABCA1 phospholipid-transporting ATPase activity, apo/lipoprotein lipidation, cholesterol efflux, localization, and disease context.
- id: file:human/ABCA1/ABCA1-notes.md
  title: Manual ABCA1 review notes
  findings: []
  reference_review:
    relevance: MEDIUM
    correctness: VERIFIED
    review_notes: Manual notes document the deep-research timeout and summarize cached UniProt, GOA, Reactome, and publication evidence used for this review.
core_functions:
- molecular_function:
    id: GO:0140326
    label: ATPase-coupled intramembrane lipid transporter activity
  description: ABCA1 uses ATP binding and hydrolysis to translocate phospholipids across membrane leaflets, with direct support for phosphatidylcholine, phosphatidylserine, and sphingomyelin movement and for extracellular phospholipid extraction at the plasma membrane.
  directly_involved_in:
  - id: GO:0045332
    label: phospholipid translocation
  - id: GO:0033700
    label: phospholipid efflux
  - id: GO:0099039
    label: sphingolipid translocation
  locations:
  - id: GO:0005886
    label: plasma membrane
  - id: GO:0009986
    label: cell surface
  - id: GO:0005768
    label: endosome
  supported_by:
  - reference_id: file:human/ABCA1/ABCA1-uniprot.txt
    supporting_text: Catalyzes the translocation of specific phospholipids
  - reference_id: PMID:24097981
    supporting_text: exported or flipped phosphatidylcholine, phosphatidylserine, and sphingomyelin
  - reference_id: PMID:24097981
    supporting_text: The same phospholipids stimulated the ATPase activity of these ABCA transporters
  - reference_id: PMID:35974019
    supporting_text: outer face of the plasma membrane and forces it through its gateway and annulus
- molecular_function:
    id: GO:0034188
    label: apolipoprotein A-I receptor activity
  description: ABCA1 binds apoA-I and other exchangeable apolipoproteins, including APOE, to drive cellular cholesterol and phospholipid efflux, nascent HDL particle assembly, and reverse cholesterol transport. This lipidation activity is the ABCA1 function most directly connected to APOE biology.
  directly_involved_in:
  - id: GO:0033344
    label: cholesterol efflux
  - id: GO:0034380
    label: high-density lipoprotein particle assembly
  - id: GO:0043691
    label: reverse cholesterol transport
  - id: GO:0090108
    label: positive regulation of high-density lipoprotein particle assembly
  - id: GO:0042632
    label: cholesterol homeostasis
  locations:
  - id: GO:0005886
    label: plasma membrane
  - id: GO:0009986
    label: cell surface
  - id: GO:0030139
    label: endocytic vesicle
  supported_by:
  - reference_id: PMID:10525055
    supporting_text: reduces apolipoprotein-mediated lipid efflux
  - reference_id: PMID:11162594
    supporting_text: ABCAI-mediated cellular binding of apolipoproteins and lipid efflux
  - reference_id: PMID:12084722
    supporting_text: direct interaction with apolipoprotein A-I
  - reference_id: PMID:14754908
    supporting_text: apoE3-mediated cholesterol efflux
  - reference_id: PMID:14754908
    supporting_text: nascent apoE3/cholesterol/phospholipid complexes
- molecular_function:
    id: GO:0120020
    label: cholesterol transfer activity
  description: ABCA1 contributes to cholesterol movement out of cells and away from intracellular pools, limiting cholesterol storage and promoting HDL-associated lipid removal. This cholesterol-efflux role is supported by Tangier/familial HDL-deficiency genetics and cellular efflux assays, although the direct transported lipid substrate is best established for phospholipids.
  directly_involved_in:
  - id: GO:0030301
    label: cholesterol transport
  - id: GO:0033344
    label: cholesterol efflux
  - id: GO:0032367
    label: intracellular cholesterol transport
  - id: GO:0010887
    label: negative regulation of cholesterol storage
  - id: GO:0008203
    label: cholesterol metabolic process
  locations:
  - id: GO:0005886
    label: plasma membrane
  - id: GO:0005768
    label: endosome
  supported_by:
  - reference_id: PMID:10431236
    supporting_text: intracellular cholesterol transport
  - reference_id: PMID:10431236
    supporting_text: cholesterol efflux regulatory protein
  - reference_id: PMID:10525055
    supporting_text: cellular cholesterol removal
  - reference_id: PMID:19556522
    supporting_text: lipids from the late endosomal or lysosomal compartment
proposed_new_terms: []
suggested_questions:
- question: Which Alzheimer-relevant ABCA1 variants primarily impair apoE lipidation versus ATP-coupled phospholipid translocation, cell-surface localization, or endosomal trafficking?
  experts:
  - ABC transporter experts
  - Alzheimer lipid biology experts
- question: Should ABCA1 apoA-I-triggered Cdc42/cAMP signaling be curated as a secondary signaling branch, or only retained when directly tied to lipid efflux assays?
  experts:
  - GO signaling curators
  - lipid transport curators
- question: How should brain-cell-type ABCA1 activity be represented for astrocytes, microglia, neurons, and vascular cells when the strongest biochemical evidence comes from macrophage/fibroblast systems?
  experts:
  - neuroglia lipid metabolism experts
  - Alzheimer genetics experts
suggested_experiments:
- description: Measure apoE isoform lipidation, cholesterol efflux, and phospholipid export in endogenous human astrocyte and microglial ABCA1 knockout/rescue systems.
  hypothesis: ABCA1 Alzheimer-relevant effects are driven by coupled apoE lipidation and phospholipid/cholesterol efflux rather than by generic signaling outputs.
  experiment_type: endogenous brain-cell lipidation and efflux assay
- description: Separate ABCA1 phosphatidylcholine/phosphatidylserine/sphingomyelin translocation from cholesterol efflux using purified transporter reconstitution and matched cell-surface localization mutants.
  hypothesis: Direct phospholipid translocation is the proximal transporter activity that enables downstream cholesterol efflux and HDL particle assembly.
  experiment_type: reconstituted transporter and localization-mutant assay