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.
| 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. Proposed replacements: ATPase-coupled intramembrane lipid transporter activity |
| 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-1Ξ² 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-1Ξ² 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-1Ξ² 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. Proposed replacements: ATPase-coupled intramembrane lipid transporter activity |
| GO:0023061 signal release | ISS PMID:29937375 Chlamydia pneumoniae Hijacks a Host Autoregulatory IL-1Ξ² 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-1Ξ² 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. |
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Download this section (compressed HTML)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
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
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