ABCA3 is a full-length ATP-binding cassette phospholipid transporter concentrated in the limiting membrane of alveolar lamellar bodies in type II epithelial cells. Its two nucleotide-binding domains couple ATP utilization to lipid translocation, supplying phosphatidylcholine-rich surfactant membranes and supporting lamellar-body formation and surfactant homeostasis. Phosphatidylglycerol handling is also strongly implicated by mammalian loss-of-function studies. Human cellular transport assays and structures support lipid export toward the lamellar-body lumen, although the detailed substrate selectivity and leaflet-resolved mechanism remain incompletely characterized. Biallelic loss-of-function variants cause pulmonary surfactant dysfunction ranging from severe neonatal respiratory failure to interstitial lung disease. ABCA3 also mediates miltefosine efflux in human macrophages.
| GO Term | Evidence | Action | Reason |
|---|---|---|---|
| GO:0005319 lipid carrier activity | IBA GO_REF:0000033 | ACCEPT | Summary: ABCA3 is an ATP-dependent membrane lipid carrier. Reason: GO_REF:0000033 is consistent with the broad lipid-carrier definition. The PAINT node PTN000442469 supports inherited ABCA lipid transport; the human target is itself among the experimental descendants, which is expected rather than circular. No target-specific loss of this function is evident. Human vesicle-loading assays (PMID:17574245; PMID:28887056) and the ATP-bound structure (PMID:35394827) establish the more specific mechanism represented separately by GO:0140326. Propagation Review Root cause: NO FAILURE CORE Sources checked: PANTHER:PTN000442469 SUPPORTS TRANSFER PAINT ancestral node for the inherited ABCA-family activity; direct human transport evidence supports retention. No donor-count or target-self-inclusion objection is made. |
| GO:0005319 lipid carrier activity | TAS Reactome:R-HSA-5683672 | ACCEPT | Summary: ABCA3 is an ATP-dependent membrane lipid carrier. Reason: Reactome:R-HSA-5683672 is consistent with the broad lipid-carrier definition. The Reactome event describes failure of lipid delivery by disease-associated ABCA3 variants. This mutant context does not negate the corresponding wild-type activity. Human vesicle-loading assays (PMID:17574245; PMID:28887056) and the ATP-bound structure (PMID:35394827) establish the more specific mechanism represented separately by GO:0140326. |
| GO:0005319 lipid carrier activity | TAS Reactome:R-HSA-5683714 | ACCEPT | Summary: ABCA3 is an ATP-dependent membrane lipid carrier. Reason: Reactome:R-HSA-5683714 is consistent with the broad lipid-carrier definition. The Reactome event describes normal ABCA3-dependent lipid delivery. Human vesicle-loading assays (PMID:17574245; PMID:28887056) and the ATP-bound structure (PMID:35394827) establish the more specific mechanism represented separately by GO:0140326. |
| GO:0005319 lipid carrier activity | TAS Reactome:R-HSA-5688397 | ACCEPT | Summary: ABCA3 is an ATP-dependent membrane lipid carrier. Reason: Reactome:R-HSA-5688397 is consistent with the broad lipid-carrier definition. The Reactome event describes failure of lipid delivery by disease-associated ABCA3 variants. This mutant context does not negate the corresponding wild-type activity. Human vesicle-loading assays (PMID:17574245; PMID:28887056) and the ATP-bound structure (PMID:35394827) establish the more specific mechanism represented separately by GO:0140326. |
| GO:0005524 ATP binding | IEA GO_REF:0000002 | ACCEPT | Summary: The two ABCA3 nucleotide-binding domains bind ATP. Reason: The InterPro ATP-binding cassette mappings agree with nucleotide trapping and ATP-binding measurements (PMID:16959783) and two bound ATP molecules in the human structure (PMID:35394827). ATP binding is a necessary component of its transport cycle. Propagation Review Root cause: NO FAILURE CORE Sources checked: InterPro:IPR003439 SUPPORTS TRANSFER The recorded ABCA/ABC nucleotide-binding or transmembrane feature agrees with the experimentally resolved human transporter architecture. InterPro:IPR017871 SUPPORTS TRANSFER The recorded ABCA/ABC nucleotide-binding or transmembrane feature agrees with the experimentally resolved human transporter architecture. |
| GO:0005576 extracellular region | HDA PMID:22664934 Comparison of tear protein levels in breast cancer patients ... | MARK AS OVER ANNOTATED | Summary: ABCA3 was detected in the tear-fluid proteomic survey. Reason: The publisher Table II in PMID:22664934 explicitly lists ABCA3_HUMAN (https://www.spandidos-publications.com/10.3892/or.2012.1849). This establishes detection in a tear-fluid sample, but neither physiological residence in the extracellular region nor a secreted form. Vesicular or shed membrane material could explain recovery; retain the detection as evidence while marking the physiological location inference as over-annotated. The local extraction includes article body sections but omits the ABCA3 table cell; the public publisher table supplies the target-specific identification. A pooled-sampling sentence alone does not support that identification. Supporting Evidence: |
| GO:0005737 cytoplasm | IEA GO_REF:0000117 | MODIFY | Summary: The broad compartment annotation can be refined to the alveolar lamellar-body membrane. Reason: The inferred broad cellular compartment is compatible with ABCA3, but human immunoelectron microscopy localizes the protein to the limiting membrane of lamellar bodies (PMID:11718719; PMID:11940594). Refine this compatible broad location to the directly demonstrated functional membrane compartment; the original broad location is not contradicted. Propagation Review Root cause: TERM SCOPING PROBLEM Failure modes: GRANULARITY MISMATCH Sources checked: ARBA:ARBA00026971 SUPPORTS TRANSFER The ARBA assertion is independently assessed against human transport/localization evidence; its broad compartment is refined where indicated. Proposed replacements: alveolar lamellar body membrane |
| GO:0005765 lysosomal membrane | EXP PMID:16959783 Characterization and classification of ATP-binding cassette ... | KEEP AS NON CORE | Summary: ABCA3 occurs in lysosomal or lysosome-related vesicular membranes during trafficking and in cellular models. Reason: PMID:16959783 follows wild-type ABCA3 into LAMP3-positive vesicles in HEK293 cells. Independent human-cell work explicitly identifies both lysosomal and lamellar-body membranes (PMID:16415354). Retain the endolysosomal context; the primary differentiated alveolar functional site is the lamellar-body limiting membrane, and a lamellar body should not simply be equated with an ordinary lysosome. |
| GO:0005765 lysosomal membrane | EXP PMID:17574245 ABCA3-mediated choline-phospholipids uptake into intracellul... | KEEP AS NON CORE | Summary: ABCA3 occurs in lysosomal or lysosome-related vesicular membranes during trafficking and in cellular models. Reason: PMID:17574245 measures choline-lipid uptake into LAMP3-positive vesicles in A549 cells. Independent human-cell work explicitly identifies both lysosomal and lamellar-body membranes (PMID:16415354). Retain the endolysosomal context; the primary differentiated alveolar functional site is the lamellar-body limiting membrane, and a lamellar body should not simply be equated with an ordinary lysosome. |
| GO:0005765 lysosomal membrane | EXP PMID:20863830 The surfactant lipid transporter ABCA3 is N-terminally cleav... | KEEP AS NON CORE | Summary: ABCA3 occurs in lysosomal or lysosome-related vesicular membranes during trafficking and in cellular models. Reason: PMID:20863830 describes maturation in multivesicular bodies and lamellar bodies. Independent human-cell work explicitly identifies both lysosomal and lamellar-body membranes (PMID:16415354). Retain the endolysosomal context; the primary differentiated alveolar functional site is the lamellar-body limiting membrane, and a lamellar body should not simply be equated with an ordinary lysosome. |
| GO:0005765 lysosomal membrane | EXP PMID:24142515 Disruption of N-linked glycosylation promotes proteasomal de... | KEEP AS NON CORE | Summary: ABCA3 occurs in lysosomal or lysosome-related vesicular membranes during trafficking and in cellular models. Reason: PMID:24142515 follows glycosylation-dependent vesicular targeting in A549 and primary human AT2 cells. Independent human-cell work explicitly identifies both lysosomal and lamellar-body membranes (PMID:16415354). Retain the endolysosomal context; the primary differentiated alveolar functional site is the lamellar-body limiting membrane, and a lamellar body should not simply be equated with an ordinary lysosome. |
| GO:0005765 lysosomal membrane | IEA GO_REF:0000044 | KEEP AS NON CORE | Summary: ABCA3 occurs in lysosomal or lysosome-related vesicular membranes during trafficking and in cellular models. Reason: The Swiss-Prot SL-0157 mapping reflects this endolysosomal localization. Independent human-cell work explicitly identifies both lysosomal and lamellar-body membranes (PMID:16415354). Retain the endolysosomal context; the primary differentiated alveolar functional site is the lamellar-body limiting membrane, and a lamellar body should not simply be equated with an ordinary lysosome. Propagation Review Root cause: NO FAILURE NON CORE Sources checked: UniProtKB-SubCell:SL-0157 SUPPORTS TRANSFER The Swiss-Prot compartment mapping is consistent with microscopy and endolysosomal maturation; lamellar bodies and ordinary lysosomes remain distinct contexts. |
| GO:0005770 late endosome | IDA PMID:27177387 Tools to explore ABCA3 mutations causing interstitial lung d... | KEEP AS NON CORE | Summary: Late endosomal localization is consistent with ABCA3 vesicle maturation. Reason: PMID:27177387 is the source localization study; its abstract does not resolve the compartment markers. The accessible full text of PMID:28887056 explicitly reports ABCA3/CD63 colocalization and identifies CD63 as a late-endosome and lamellar-body marker, citing the original study. Retain this trafficking/model-system location without making late endosomes the principal mature alveolar location. |
| GO:0005886 plasma membrane | IDA PMID:11718719 ABCA3 is a lamellar body membrane protein in human lung alve... | UNDECIDED | Summary: The source-specific plasma-membrane localization needs full-text verification. Reason: The accessible abstract of PMID:11718719 reports predominantly lamellar-body limiting-membrane labeling but does not resolve the minority plasma-membrane signal. The original full text could not be retrieved. This is not grounds to reject the curator: human macrophage surface ABCA3 is independently supported by PMID:26903515, but that does not verify this lung-study annotation. |
| GO:0005886 plasma membrane | IDA PMID:23137377 Quantitative targeted absolute proteomic analysis of transpo... | KEEP AS NON CORE | Summary: Plasma-membrane fraction proteomics detected ABCA3 in the hCMEC/D3 cell line. Reason: PMID:23137377 explicitly reports ABCA3 detection only in hCMEC/D3 cells in the cell-line versus human brain-microvessel comparison. Retain the measured model-system location without extrapolating to normal brain endothelium or treating it as the pulmonary core location. |
| GO:0006855 xenobiotic transmembrane transport | IMP PMID:26903515 Functional Validation of ABCA3 as a Miltefosine Transporter ... | KEEP AS NON CORE | Summary: ABCA3 mediates miltefosine efflux in human macrophages. Reason: PMID:26903515 combines ABCA3 knockdown, radiolabeled miltefosine accumulation, cytotoxicity and macrophage localization. It supports this xenobiotic-transport activity in a defined pharmacological and cell-type context; it does not establish indiscriminate multidrug export or replace surfactant lipid transport as the principal physiological function. |
| GO:0006869 lipid transport | IBA GO_REF:0000033 | ACCEPT | Summary: Lipid transport is the central activity-dependent process of ABCA3. Reason: The PAINT ancestral node PTN000442469 captures a conserved ABCA-family lipid-transport function, corroborated directly in human ABCA3. Cellular choline-phospholipid uptake and TopFluor-PC accumulation support active loading of intracellular vesicles (PMID:17574245; PMID:28887056). Propagation Review Root cause: NO FAILURE CORE Sources checked: PANTHER:PTN000442469 SUPPORTS TRANSFER PAINT ancestral node for the inherited ABCA-family activity; direct human transport evidence supports retention. No donor-count or target-self-inclusion objection is made. |
| GO:0006869 lipid transport | IEA GO_REF:0000117 | ACCEPT | Summary: Lipid transport is the central activity-dependent process of ABCA3. Reason: ARBA00027046 agrees with direct human ABCA3 phospholipid transport measurements. Cellular choline-phospholipid uptake and TopFluor-PC accumulation support active loading of intracellular vesicles (PMID:17574245; PMID:28887056). Propagation Review Root cause: NO FAILURE CORE Sources checked: ARBA:ARBA00027046 SUPPORTS TRANSFER The ARBA assertion is independently assessed against human transport/localization evidence; its broad compartment is refined where indicated. |
| GO:0006869 lipid transport | TAS Reactome:R-HSA-1369062 | ACCEPT | Summary: Lipid transport is the central activity-dependent process of ABCA3. Reason: Reactome R-HSA-1369062 is a broad lipid-homeostasis pathway; the specific ABCA3 transport step is established independently. Cellular choline-phospholipid uptake and TopFluor-PC accumulation support active loading of intracellular vesicles (PMID:17574245; PMID:28887056). |
| GO:0008559 ABC-type xenobiotic transporter activity | IEA GO_REF:0000003 | KEEP AS NON CORE | Summary: ABCA3 mediates miltefosine efflux in human macrophages. Reason: PMID:26903515 combines ABCA3 knockdown, radiolabeled miltefosine accumulation, cytotoxicity and macrophage localization. It supports this xenobiotic-transport activity in a defined pharmacological and cell-type context; it does not establish indiscriminate multidrug export or replace surfactant lipid transport as the principal physiological function. Propagation Review Root cause: NO FAILURE NON CORE Sources checked: EC:7.6.2.2 SUPPORTS TRANSFER The recorded source is compatible with the human ABCA3 transport mechanism or localization, corroborated by the primary studies cited in this review. |
| GO:0008559 ABC-type xenobiotic transporter activity | IMP PMID:26903515 Functional Validation of ABCA3 as a Miltefosine Transporter ... | KEEP AS NON CORE | Summary: ABCA3 mediates miltefosine efflux in human macrophages. Reason: PMID:26903515 combines ABCA3 knockdown, radiolabeled miltefosine accumulation, cytotoxicity and macrophage localization. It supports this xenobiotic-transport activity in a defined pharmacological and cell-type context; it does not establish indiscriminate multidrug export or replace surfactant lipid transport as the principal physiological function. |
| GO:0009410 response to xenobiotic stimulus | TAS PMID:8706931 Primary structure of a novel ABC transporter with a chromoso... | KEEP AS NON CORE | Summary: A xenobiotic response is supported for miltefosine-exposed human macrophages. Reason: The original cloning paper PMID:8706931 proposed xenobiotic resistance from sequence/family and genomic context rather than demonstrating it. Later PMID:26903515 directly shows miltefosine induction and ABCA3-dependent drug efflux. Retain a contextual response annotation using that independent evidence; do not present the 1996 speculation as an experimental transport result. |
| GO:0010875 positive regulation of cholesterol efflux | IMP PMID:25817392 ABCA3 protects alveolar epithelial cells against free choles... | KEEP AS NON CORE | Summary: ABCA3 expression promotes cellular cholesterol clearance in an epithelial-cell model. Reason: PMID:25817392 reports lower free cholesterol, SREBP activation and protection against cholesterol loading, with impairment by disease variants. Retain the cholesterol-efflux/homeostatic effect as secondary to the principal surfactant function. These cellular endpoints do not by themselves establish purified ABCA3 cholesterol translocation or its substrate kinetics. Reduced free cholesterol could also reflect sequestration into lamellar-body-like vesicles rather than increased efflux to an extracellular acceptor; the accessible abstract does not resolve that distinction. The existing experimental annotation is retained as non-core without asserting that specific mechanism. |
| GO:0012505 endomembrane system | IEA GO_REF:0000117 | MODIFY | Summary: The broad compartment annotation can be refined to the alveolar lamellar-body membrane. Reason: The inferred broad cellular compartment is compatible with ABCA3, but human immunoelectron microscopy localizes the protein to the limiting membrane of lamellar bodies (PMID:11718719; PMID:11940594). Refine this compatible broad location to the directly demonstrated functional membrane compartment; the original broad location is not contradicted. Propagation Review Root cause: TERM SCOPING PROBLEM Failure modes: GRANULARITY MISMATCH Sources checked: ARBA:ARBA00028953 SUPPORTS TRANSFER The ARBA assertion is independently assessed against human transport/localization evidence; its broad compartment is refined where indicated. Proposed replacements: alveolar lamellar body membrane |
| GO:0015914 phospholipid transport | IMP PMID:28887056 Quantification of volume and lipid filling of intracellular ... | ACCEPT | Summary: ABCA3 actively loads phosphatidylcholine into intracellular vesicles. Reason: PMID:28887056 measures concentration- and time-dependent TopFluor-PC accumulation in ABCA3-positive A549 vesicles. Vanadate and a disease variant impair loading. The full text acknowledges vanadate is not ABCA3-specific, so the conclusion rests on convergent cell and mutation evidence rather than inhibitor specificity alone. |
| GO:0016020 membrane | IEA GO_REF:0000002 | MODIFY | Summary: The broad compartment annotation can be refined to the alveolar lamellar-body membrane. Reason: The inferred broad cellular compartment is compatible with ABCA3, but human immunoelectron microscopy localizes the protein to the limiting membrane of lamellar bodies (PMID:11718719; PMID:11940594). Refine this compatible broad location to the directly demonstrated functional membrane compartment; the original broad location is not contradicted. Propagation Review Root cause: TERM SCOPING PROBLEM Failure modes: GRANULARITY MISMATCH Sources checked: InterPro:IPR013525 SUPPORTS TRANSFER The recorded ABCA/ABC nucleotide-binding or transmembrane feature agrees with the experimentally resolved human transporter architecture. InterPro:IPR026082 SUPPORTS TRANSFER The recorded ABCA/ABC nucleotide-binding or transmembrane feature agrees with the experimentally resolved human transporter architecture. Proposed replacements: alveolar lamellar body membrane |
| GO:0016887 ATP hydrolysis activity | IDA PMID:16959783 Characterization and classification of ATP-binding cassette ... | ACCEPT | Summary: ATP hydrolysis powers the ABCA3 transport cycle. Reason: PMID:16959783 measures nucleotide trapping and impaired hydrolysis in pathogenic variants; PMID:35394827 measures ATPase activity of purified human ABCA3 and resolves nucleotide-bound conformations. The ATP-hydrolysis term is a true catalytic subactivity of the lipid transporter. |
| GO:0016887 ATP hydrolysis activity | IEA GO_REF:0000002 | ACCEPT | Summary: ATP hydrolysis powers the ABCA3 transport cycle. Reason: PMID:16959783 measures nucleotide trapping and impaired hydrolysis in pathogenic variants; PMID:35394827 measures ATPase activity of purified human ABCA3 and resolves nucleotide-bound conformations. The ATP-hydrolysis term is a true catalytic subactivity of the lipid transporter. Propagation Review Root cause: NO FAILURE CORE Sources checked: InterPro:IPR003439 SUPPORTS TRANSFER The recorded ABCA/ABC nucleotide-binding or transmembrane feature agrees with the experimentally resolved human transporter architecture. InterPro:IPR017871 SUPPORTS TRANSFER The recorded ABCA/ABC nucleotide-binding or transmembrane feature agrees with the experimentally resolved human transporter architecture. |
| GO:0030324 lung development | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: ABCA3-dependent surfactant and lamellar-body formation support lung maturation. Reason: The mouse Abca3 donor has experimental lung-development annotations from PMID:17540762 and PMID:20190032. These studies establish fetal maturation and postnatal structural consequences of loss of surfactant lipid handling. Human loss-of-function disease supports conservation (PMID:15044640), but developmental morphology is downstream of the transporter rather than a separate core signaling activity. Propagation Review Root cause: NO FAILURE NON CORE Sources checked: UniProtKB:Q8R420 SUPPORTS TRANSFER Mouse Abca3 donor; live QuickGO traces lung-development IMP evidence to PMID:17540762 and PMID:20190032. Conserved developmental consequences are retained as non-core. ensembl:ENSMUSP00000078544 SUPPORTS TRANSFER Mouse Abca3 donor; live QuickGO traces lung-development IMP evidence to PMID:17540762 and PMID:20190032. Conserved developmental consequences are retained as non-core. |
| GO:0030324 lung development | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: ABCA3-dependent surfactant and lamellar-body formation support lung maturation. Reason: The mouse Abca3 donor has experimental lung-development annotations from PMID:17540762 and PMID:20190032. These studies establish fetal maturation and postnatal structural consequences of loss of surfactant lipid handling. Human loss-of-function disease supports conservation (PMID:15044640), but developmental morphology is downstream of the transporter rather than a separate core signaling activity. Propagation Review Root cause: NO FAILURE NON CORE Sources checked: UniProtKB:Q8R420 SUPPORTS TRANSFER Mouse Abca3 donor; live QuickGO traces lung-development IMP evidence to PMID:17540762 and PMID:20190032. Conserved developmental consequences are retained as non-core. |
| GO:0030659 cytoplasmic vesicle membrane | EXP PMID:22673903 Quantitative maps of protein phosphorylation sites across 14... | UNDECIDED | Summary: The cytoplasmic-vesicle membrane location is plausible, but this phosphoproteomic citation is unresolved. Reason: PMID:22673903 includes both a rat-organ atlas and human skeletal-muscle validation. The accessible full text does not identify the source-specific ABCA3 vesicle-localization evidence; the relevant supplemental assignment was not recovered. Retain uncertainty about this evidence link, not a claim of wrong organism or paralog. Independent studies clearly support ABCA3 vesicle membranes. |
| GO:0030659 cytoplasmic vesicle membrane | EXP PMID:27177387 Tools to explore ABCA3 mutations causing interstitial lung d... | ACCEPT | Summary: ABCA3 occupies the limiting membrane of intracellular lipid-storage vesicles. Reason: PMID:27177387 is consistent with the human ABCA3 vesicular location. Imaging, membrane fractionation and maturation studies establish membrane-associated ABCA3 in lamellar bodies and their precursor vesicles; the core synthesis uses the specific alveolar lamellar-body membrane term (PMID:11718719; PMID:20863830). |
| GO:0030659 cytoplasmic vesicle membrane | EXP PMID:31473345 Metabolic labelling of choline phospholipids probes ABCA3 tr... | ACCEPT | Summary: ABCA3 occupies the limiting membrane of intracellular lipid-storage vesicles. Reason: PMID:31473345 is consistent with the human ABCA3 vesicular location. Imaging, membrane fractionation and maturation studies establish membrane-associated ABCA3 in lamellar bodies and their precursor vesicles; the core synthesis uses the specific alveolar lamellar-body membrane term (PMID:11718719; PMID:20863830). |
| GO:0030659 cytoplasmic vesicle membrane | IDA PMID:16959783 Characterization and classification of ATP-binding cassette ... | ACCEPT | Summary: ABCA3 occupies the limiting membrane of intracellular lipid-storage vesicles. Reason: PMID:16959783 is consistent with the human ABCA3 vesicular location. Imaging, membrane fractionation and maturation studies establish membrane-associated ABCA3 in lamellar bodies and their precursor vesicles; the core synthesis uses the specific alveolar lamellar-body membrane term (PMID:11718719; PMID:20863830). |
| GO:0030659 cytoplasmic vesicle membrane | IDA PMID:17574245 ABCA3-mediated choline-phospholipids uptake into intracellul... | ACCEPT | Summary: ABCA3 occupies the limiting membrane of intracellular lipid-storage vesicles. Reason: PMID:17574245 is consistent with the human ABCA3 vesicular location. Imaging, membrane fractionation and maturation studies establish membrane-associated ABCA3 in lamellar bodies and their precursor vesicles; the core synthesis uses the specific alveolar lamellar-body membrane term (PMID:11718719; PMID:20863830). |
| GO:0030659 cytoplasmic vesicle membrane | IDA PMID:20863830 The surfactant lipid transporter ABCA3 is N-terminally cleav... | ACCEPT | Summary: ABCA3 occupies the limiting membrane of intracellular lipid-storage vesicles. Reason: PMID:20863830 is consistent with the human ABCA3 vesicular location. Imaging, membrane fractionation and maturation studies establish membrane-associated ABCA3 in lamellar bodies and their precursor vesicles; the core synthesis uses the specific alveolar lamellar-body membrane term (PMID:11718719; PMID:20863830). |
| GO:0030659 cytoplasmic vesicle membrane | IEA GO_REF:0000044 | ACCEPT | Summary: ABCA3 occupies the limiting membrane of intracellular lipid-storage vesicles. Reason: GO_REF:0000044 is consistent with the human ABCA3 vesicular location. Imaging, membrane fractionation and maturation studies establish membrane-associated ABCA3 in lamellar bodies and their precursor vesicles; the core synthesis uses the specific alveolar lamellar-body membrane term (PMID:11718719; PMID:20863830). Propagation Review Root cause: NO FAILURE CORE Sources checked: UniProtKB-SubCell:SL-0089 SUPPORTS TRANSFER The Swiss-Prot compartment mapping is consistent with microscopy and endolysosomal maturation; lamellar bodies and ordinary lysosomes remain distinct contexts. |
| GO:0031340 positive regulation of vesicle fusion | IEA GO_REF:0000107 | UNDECIDED | Summary: A rat-derived positive-vesicle-fusion annotation could not be verified mechanistically. Reason: QuickGO donor tracing recovers rat Abca3 (UniProtKB:A0A0G2K1Q8) with IMP evidence from PMID:15904872. The cached abstract describes annexin A7 membrane-fusion assays; the full text was inaccessible. It may contain ABCA3 experiments not visible in the abstract. Do not call this a misattribution or infer that ABCA3 is itself a fusion regulator from its presence in lamellar bodies. Propagation Review Root cause: UNRESOLVED Sources checked: UniProtKB:A0A0G2K1Q8 UNRESOLVED Rat Abca3 donor traces to IMP PMID:15904872. Only the annexin-A7-focused abstract was accessible, so the precise ABCA3 fusion experiment and its transfer remain unresolved. ensembl:ENSRNOP00000071944 UNRESOLVED Rat Abca3 donor traces to IMP PMID:15904872. Only the annexin-A7-focused abstract was accessible, so the precise ABCA3 fusion experiment and its transfer remain unresolved. |
| GO:0031902 late endosome membrane | EXP PMID:27177387 Tools to explore ABCA3 mutations causing interstitial lung d... | KEEP AS NON CORE | Summary: ABCA3 passes through late endosomal membrane compartments. Reason: The source annotation and Swiss-Prot SL-0151 mapping are consistent with ABCA3/CD63-positive vesicles described in the accessible full text of PMID:28887056 and multivesicular-body maturation in PMID:20863830. This is a trafficking/model-system context rather than a second primary molecular function. |
| GO:0031902 late endosome membrane | IEA GO_REF:0000044 | KEEP AS NON CORE | Summary: ABCA3 passes through late endosomal membrane compartments. Reason: The source annotation and Swiss-Prot SL-0151 mapping are consistent with ABCA3/CD63-positive vesicles described in the accessible full text of PMID:28887056 and multivesicular-body maturation in PMID:20863830. This is a trafficking/model-system context rather than a second primary molecular function. Propagation Review Root cause: NO FAILURE NON CORE Sources checked: UniProtKB-SubCell:SL-0151 SUPPORTS TRANSFER The Swiss-Prot compartment mapping is consistent with microscopy and endolysosomal maturation; lamellar bodies and ordinary lysosomes remain distinct contexts. |
| GO:0032368 regulation of lipid transport | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: ABCA3 loss perturbs lipid transport and biosynthetic feedback in mouse alveolar cells. Reason: The mouse donor annotations trace to conditional Abca3 deletion (PMID:20190032), which decreases expression of lipid-synthesis and transport genes and alters FOXA2/CEBPA expression. Retain the secondary regulatory/homeostatic effect, without treating ABCA3 as a transcription factor or lipid-synthesis enzyme. Its direct molecular activity is ATP-dependent lipid translocation. Propagation Review Root cause: NO FAILURE NON CORE Sources checked: UniProtKB:Q8R420 SUPPORTS TRANSFER Mouse Abca3 donor; PMID:20190032 supports altered lipid-gene expression and biosynthetic feedback, not a second core enzyme activity. ensembl:ENSMUSP00000078544 SUPPORTS TRANSFER Mouse Abca3 donor; PMID:20190032 supports altered lipid-gene expression and biosynthetic feedback, not a second core enzyme activity. |
| GO:0032464 positive regulation of protein homooligomerization | IDA PMID:27352740 Homooligomerization of ABCA3 and its functional significance... | MODIFY | Summary: ABCA3 forms homooligomers; the measured event is its own assembly. Reason: PMID:27352740 demonstrates ABCA3 self-association by blue-native PAGE, size-exclusion chromatography, co-immunoprecipitation and BRET. The accessible full text discusses, but does not establish, the functional requirement of oligomerization for transport. Replace positive regulation of oligomerization with protein homooligomerization: the evidence concerns ABCA3 subunits assembling, not an independent regulatory action on another assembly process. Proposed replacements: protein homooligomerization |
| GO:0032585 multivesicular body membrane | IEA GO_REF:0000044 | KEEP AS NON CORE | Summary: ABCA3 is present in precursor multivesicular-body membranes. Reason: The SL-0175 mapping is directly consistent with PMID:20863830, which places mature ABCA3 processing inside multivesicular bodies and lamellar bodies. This trafficking compartment is retained alongside the mature alveolar lamellar-body site. Propagation Review Root cause: NO FAILURE NON CORE Sources checked: UniProtKB-SubCell:SL-0175 SUPPORTS TRANSFER The Swiss-Prot compartment mapping is consistent with microscopy and endolysosomal maturation; lamellar bodies and ordinary lysosomes remain distinct contexts. |
| GO:0034204 lipid translocation | IEA GO_REF:0000120 | ACCEPT | Summary: ABCA3 carries out ATP-coupled lipid translocation across a membrane. Reason: The automated GO:0140326 source is supported by cellular lipid-loading experiments and the human structural transport model (PMID:35394827). The accompanying GO:0140345 source has an unresolved/opposite-direction specificity and is separately refined here; the broad lipid-translocation process remains supported independently. Propagation Review Root cause: NO FAILURE CORE Sources checked: GO:0140326 SUPPORTS TRANSFER The ATPase-coupled intramembrane lipid-carrier source directly entails lipid translocation and agrees with human ABCA3 transport evidence. GO:0140345 UNRESOLVED This source has exoplasmic-to-cytosolic directionality that is not supported for ABCA3. The broader translocation process is retained through independent GO:0140326 and human transport evidence. |
| GO:0042599 lamellar body | IDA PMID:27177387 Tools to explore ABCA3 mutations causing interstitial lung d... | ACCEPT | Summary: ABCA3 is a lamellar-body membrane protein. Reason: The original PMID:27177387 study measures malformed lamellar bodies in K1388N-expressing cells. Human immunoelectron microscopy independently establishes the native location (PMID:11718719); this parent organelle term is valid while the core synthesis specifies its membrane. |
| GO:0042626 ATPase-coupled transmembrane transporter activity | IBA GO_REF:0000033 | ACCEPT | Summary: ABCA3 is an ATP-driven primary active transporter. Reason: The PAINT PTN000442469 assertion agrees with direct ABCA3 ATPase and lipid-loading measurements. Target ABCA3 appearing among descendant evidence is legitimate experimental grounding, not circular transfer. The more specific lipid-carrier activity is already represented in the annotation set. Propagation Review Root cause: NO FAILURE CORE Sources checked: PANTHER:PTN000442469 SUPPORTS TRANSFER PAINT ancestral node for the inherited ABCA-family activity; direct human transport evidence supports retention. No donor-count or target-self-inclusion objection is made. |
| GO:0042908 xenobiotic transport | IMP PMID:26903515 Functional Validation of ABCA3 as a Miltefosine Transporter ... | KEEP AS NON CORE | Summary: ABCA3 mediates miltefosine efflux in human macrophages. Reason: PMID:26903515 combines ABCA3 knockdown, radiolabeled miltefosine accumulation, cytotoxicity and macrophage localization. It supports this xenobiotic-transport activity in a defined pharmacological and cell-type context; it does not establish indiscriminate multidrug export or replace surfactant lipid transport as the principal physiological function. |
| GO:0043129 surfactant homeostasis | IEA GO_REF:0000107 | ACCEPT | Summary: ABCA3 supplies the surfactant lipid pool and maintains surfactant homeostasis. Reason: Mouse Abca3 knockout studies (PMID:17142808; PMID:17267394; PMID:17577581) show abnormal or absent lamellar bodies and severe surfactant lipid deficiency. Human cell transport experiments and isogenic patient-derived alveolar models (PMID:38226623) support conservation. ABCA3 participates directly by moving the lipids into their storage organelle. Propagation Review Root cause: NO FAILURE CORE Sources checked: UniProtKB:Q8R420 SUPPORTS TRANSFER Mouse Abca3 donor; experimental surfactant-homeostasis evidence includes PMID:17142808, PMID:17267394 and PMID:17577581, with direct human corroboration. ensembl:ENSMUSP00000078544 SUPPORTS TRANSFER Mouse Abca3 donor; experimental surfactant-homeostasis evidence includes PMID:17142808, PMID:17267394 and PMID:17577581, with direct human corroboration. |
| GO:0043129 surfactant homeostasis | ISS GO_REF:0000024 | ACCEPT | Summary: ABCA3 supplies the surfactant lipid pool and maintains surfactant homeostasis. Reason: Mouse Abca3 knockout studies (PMID:17142808; PMID:17267394; PMID:17577581) show abnormal or absent lamellar bodies and severe surfactant lipid deficiency. Human cell transport experiments and isogenic patient-derived alveolar models (PMID:38226623) support conservation. ABCA3 participates directly by moving the lipids into their storage organelle. Propagation Review Root cause: NO FAILURE CORE Sources checked: UniProtKB:Q8R420 SUPPORTS TRANSFER Mouse Abca3 donor; experimental surfactant-homeostasis evidence includes PMID:17142808, PMID:17267394 and PMID:17577581, with direct human corroboration. |
| GO:0046470 phosphatidylcholine metabolic process | IEA GO_REF:0000107 | MODIFY | Summary: Abca3 loss alters phosphatidylcholine abundance and surfactant composition. Reason: The mouse source experiments (PMID:17267394; PMID:17142808) measure reduced surfactant lipid species after Abca3 loss. The conserved conclusion is phospholipid homeostasis, achieved through lipid transport. GO metabolic-process definitions concern chemical reactions and pathways; the lipid-composition phenotype does not establish that ABCA3 catalyzes phosphatidylcholine synthesis or degradation. Use the measured homeostatic role, without extrapolating species-level depletion into a substrate-specific catalytic reaction. Propagation Review Root cause: TERM SCOPING PROBLEM Failure modes: ROLE CONFLATION Sources checked: UniProtKB:Q8R420 SUPPORTS TRANSFER Mouse Abca3 source experiments measure surfactant lipid depletion (PMID:17267394; PMID:17142808). Transfer of the homeostatic phenotype is supported, but direct lipid chemical metabolism is not established by depletion alone. ensembl:ENSMUSP00000078544 SUPPORTS TRANSFER Mouse Abca3 source experiments measure surfactant lipid depletion (PMID:17267394; PMID:17142808). Transfer of the homeostatic phenotype is supported, but direct lipid chemical metabolism is not established by depletion alone. Proposed replacements: phospholipid homeostasis |
| GO:0046470 phosphatidylcholine metabolic process | IMP PMID:17574245 ABCA3-mediated choline-phospholipids uptake into intracellul... | MODIFY | Summary: The measured phosphatidylcholine endpoint reflects ABCA3-mediated vesicle loading. Reason: PMID:17574245 measures choline-phospholipid accumulation in ABCA3-positive intracellular vesicles. Together with the ATP-dependent transport mechanism, this supports phospholipid transport. A change in vesicular lipid content should not be read as direct chemical metabolism of phosphatidylcholine by ABCA3. Preserve the experimental result using the process it measures. Proposed replacements: phospholipid transport |
| GO:0046470 phosphatidylcholine metabolic process | IMP PMID:28887056 Quantification of volume and lipid filling of intracellular ... | MODIFY | Summary: The measured phosphatidylcholine endpoint reflects ABCA3-mediated vesicle loading. Reason: PMID:28887056 measures choline-phospholipid accumulation in ABCA3-positive intracellular vesicles. Together with the ATP-dependent transport mechanism, this supports phospholipid transport. A change in vesicular lipid content should not be read as direct chemical metabolism of phosphatidylcholine by ABCA3. Preserve the experimental result using the process it measures. Proposed replacements: phospholipid transport |
| GO:0046470 phosphatidylcholine metabolic process | ISS GO_REF:0000024 | MODIFY | Summary: Abca3 loss alters phosphatidylcholine abundance and surfactant composition. Reason: The mouse source experiments (PMID:17267394; PMID:17142808) measure reduced surfactant lipid species after Abca3 loss. The conserved conclusion is phospholipid homeostasis, achieved through lipid transport. GO metabolic-process definitions concern chemical reactions and pathways; the lipid-composition phenotype does not establish that ABCA3 catalyzes phosphatidylcholine synthesis or degradation. Use the measured homeostatic role, without extrapolating species-level depletion into a substrate-specific catalytic reaction. Propagation Review Root cause: TERM SCOPING PROBLEM Failure modes: ROLE CONFLATION Sources checked: UniProtKB:Q8R420 SUPPORTS TRANSFER Mouse Abca3 source experiments measure surfactant lipid depletion (PMID:17267394; PMID:17142808). Transfer of the homeostatic phenotype is supported, but direct lipid chemical metabolism is not established by depletion alone. Proposed replacements: phospholipid homeostasis |
| GO:0046471 phosphatidylglycerol metabolic process | IEA GO_REF:0000107 | MODIFY | Summary: Abca3 loss alters phosphatidylglycerol abundance and surfactant composition. Reason: The mouse source experiments (PMID:17267394; PMID:17142808) measure reduced surfactant lipid species after Abca3 loss. The conserved conclusion is phospholipid homeostasis, achieved through lipid transport. GO metabolic-process definitions concern chemical reactions and pathways; the lipid-composition phenotype does not establish that ABCA3 catalyzes phosphatidylglycerol synthesis or degradation. Use the measured homeostatic role, without extrapolating species-level depletion into a substrate-specific catalytic reaction. Propagation Review Root cause: TERM SCOPING PROBLEM Failure modes: ROLE CONFLATION Sources checked: UniProtKB:Q8R420 SUPPORTS TRANSFER Mouse Abca3 source experiments measure surfactant lipid depletion (PMID:17267394; PMID:17142808). Transfer of the homeostatic phenotype is supported, but direct lipid chemical metabolism is not established by depletion alone. ensembl:ENSMUSP00000078544 SUPPORTS TRANSFER Mouse Abca3 source experiments measure surfactant lipid depletion (PMID:17267394; PMID:17142808). Transfer of the homeostatic phenotype is supported, but direct lipid chemical metabolism is not established by depletion alone. Proposed replacements: phospholipid homeostasis |
| GO:0046471 phosphatidylglycerol metabolic process | ISS GO_REF:0000024 | MODIFY | Summary: Abca3 loss alters phosphatidylglycerol abundance and surfactant composition. Reason: The mouse source experiments (PMID:17267394; PMID:17142808) measure reduced surfactant lipid species after Abca3 loss. The conserved conclusion is phospholipid homeostasis, achieved through lipid transport. GO metabolic-process definitions concern chemical reactions and pathways; the lipid-composition phenotype does not establish that ABCA3 catalyzes phosphatidylglycerol synthesis or degradation. Use the measured homeostatic role, without extrapolating species-level depletion into a substrate-specific catalytic reaction. Propagation Review Root cause: TERM SCOPING PROBLEM Failure modes: ROLE CONFLATION Sources checked: UniProtKB:Q8R420 SUPPORTS TRANSFER Mouse Abca3 source experiments measure surfactant lipid depletion (PMID:17267394; PMID:17142808). Transfer of the homeostatic phenotype is supported, but direct lipid chemical metabolism is not established by depletion alone. Proposed replacements: phospholipid homeostasis |
| GO:0046618 xenobiotic export from cell | IMP PMID:26903515 Functional Validation of ABCA3 as a Miltefosine Transporter ... | KEEP AS NON CORE | Summary: ABCA3 mediates miltefosine efflux in human macrophages. Reason: PMID:26903515 combines ABCA3 knockdown, radiolabeled miltefosine accumulation, cytotoxicity and macrophage localization. It supports this xenobiotic-transport activity in a defined pharmacological and cell-type context; it does not establish indiscriminate multidrug export or replace surfactant lipid transport as the principal physiological function. |
| GO:0046890 regulation of lipid biosynthetic process | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: ABCA3 loss perturbs lipid transport and biosynthetic feedback in mouse alveolar cells. Reason: The mouse donor annotations trace to conditional Abca3 deletion (PMID:20190032), which decreases expression of lipid-synthesis and transport genes and alters FOXA2/CEBPA expression. Retain the secondary regulatory/homeostatic effect, without treating ABCA3 as a transcription factor or lipid-synthesis enzyme. Its direct molecular activity is ATP-dependent lipid translocation. Propagation Review Root cause: NO FAILURE NON CORE Sources checked: UniProtKB:Q8R420 SUPPORTS TRANSFER Mouse Abca3 donor; PMID:20190032 supports altered lipid-gene expression and biosynthetic feedback, not a second core enzyme activity. ensembl:ENSMUSP00000078544 SUPPORTS TRANSFER Mouse Abca3 donor; PMID:20190032 supports altered lipid-gene expression and biosynthetic feedback, not a second core enzyme activity. |
| GO:0051384 response to glucocorticoid | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Rat lung Abca3 expression responds to glucocorticoids. Reason: Donor tracing identifies rat Abca3 with IEP evidence from PMID:15369786. That study measures developmental and glucocorticoid-induced ABCA3 expression. Retain the regulatory response context, while recognizing that expression induction does not make ABCA3 a glucocorticoid receptor or the signaling effector upstream of its own induction. Propagation Review Root cause: NO FAILURE NON CORE Sources checked: UniProtKB:A0A0G2K1Q8 SUPPORTS TRANSFER Rat Abca3 donor; live QuickGO identifies IEP evidence from PMID:15369786 for glucocorticoid-responsive expression. This is a secondary expression response. ensembl:ENSRNOP00000071944 SUPPORTS TRANSFER Rat Abca3 donor; live QuickGO identifies IEP evidence from PMID:15369786 for glucocorticoid-responsive expression. This is a secondary expression response. |
| GO:0055085 transmembrane transport | IEA GO_REF:0000002 | ACCEPT | Summary: The ABCA3 membrane domains mediate transmembrane lipid transport. Reason: The ABCA-family InterPro mapping is broad but consistent with human ATP-dependent phospholipid-loading assays and the transporter structure. No evidence of target-specific loss or divergence contradicts this family-level process. Propagation Review Root cause: NO FAILURE CORE Sources checked: InterPro:IPR026082 SUPPORTS TRANSFER The recorded ABCA/ABC nucleotide-binding or transmembrane feature agrees with the experimentally resolved human transporter architecture. |
| GO:0055091 phospholipid homeostasis | IEA GO_REF:0000107 | ACCEPT | Summary: ABCA3-dependent lipid loading maintains the alveolar phospholipid pool. Reason: The mouse donor experiment PMID:20190032 shows altered phospholipid content and composition in lung tissue, lamellar bodies and lavage after conditional Abca3 deletion. Human ABCA3 transport and disease evidence establish conservation of this directly mediated homeostatic role. Propagation Review Root cause: NO FAILURE CORE Sources checked: UniProtKB:Q8R420 SUPPORTS TRANSFER Mouse Abca3 donor; conditional deletion directly changes phospholipid content/composition in PMID:20190032. Human lipid transport supports conservation. ensembl:ENSMUSP00000078544 SUPPORTS TRANSFER Mouse Abca3 donor; conditional deletion directly changes phospholipid content/composition in PMID:20190032. Human lipid transport supports conservation. |
| GO:0070925 organelle assembly | ISS GO_REF:0000024 | ACCEPT | Summary: ABCA3 promotes lamellar-body assembly through lipid loading. Reason: Mouse PMID:17540762 reports loss of lamellar bodies after Abca3 deletion. Human experiments in PMID:16415354 go beyond necessity: ectopic ABCA3 induces lipid-containing lamellar-body-like vesicles and endogenous knockdown impairs their formation. The transporter performs part of assembly by supplying the lipid constituents, rather than serving merely as a passive organelle marker. Propagation Review Root cause: NO FAILURE CORE Sources checked: UniProtKB:Q8R420 SUPPORTS TRANSFER Mouse Abca3 donor; PMID:17540762 supports lamellar-body biogenesis, independently corroborated by human gain- and loss-of-function experiments in PMID:16415354. |
| GO:0097208 alveolar lamellar body | IDA PMID:11718719 ABCA3 is a lamellar body membrane protein in human lung alve... | ACCEPT | Summary: Native human ABCA3 is concentrated in alveolar lamellar bodies. Reason: PMID:11718719 identifies ABCA3 in surfactant-protein-A-positive type II cells and, by immunoelectron microscopy, predominantly at the lamellar-body limiting membrane. The organelle annotation is directly supported. |
| GO:0097232 lamellar body membrane | IDA PMID:20863830 The surfactant lipid transporter ABCA3 is N-terminally cleav... | ACCEPT | Summary: The limiting membrane of alveolar lamellar bodies is the main physiological site of ABCA3. Reason: PMID:20863830 follows glycosylation, trafficking and N-terminal processing of tagged ABCA3 into mature lamellar bodies and their multivesicular precursors. This supports the limiting-membrane location established by human microscopy in PMID:11718719 and PMID:11940594. Maturation in this compartment is distinguished from ER retention of pathogenic variants. |
| GO:0097232 lamellar body membrane | TAS Reactome:R-HSA-5683672 | ACCEPT | Summary: The limiting membrane of alveolar lamellar bodies is the main physiological site of ABCA3. Reason: Reactome:R-HSA-5683672 agrees with human microscopy (PMID:11718719; PMID:11940594) and ABCA3 maturation/localization (PMID:20863830). Mutant-loss Reactome events document failure at this site, not absence of the wild-type location. Retain the location without assigning aberrant ER retention of pathogenic variants as a wild-type core function. |
| GO:0097232 lamellar body membrane | TAS Reactome:R-HSA-5683714 | ACCEPT | Summary: The limiting membrane of alveolar lamellar bodies is the main physiological site of ABCA3. Reason: Reactome:R-HSA-5683714 agrees with human microscopy (PMID:11718719; PMID:11940594) and ABCA3 maturation/localization (PMID:20863830). Mutant-loss Reactome events document failure at this site, not absence of the wild-type location. Retain the location without assigning aberrant ER retention of pathogenic variants as a wild-type core function. |
| GO:0097232 lamellar body membrane | TAS Reactome:R-HSA-5688397 | ACCEPT | Summary: The limiting membrane of alveolar lamellar bodies is the main physiological site of ABCA3. Reason: Reactome:R-HSA-5688397 agrees with human microscopy (PMID:11718719; PMID:11940594) and ABCA3 maturation/localization (PMID:20863830). Mutant-loss Reactome events document failure at this site, not absence of the wild-type location. Retain the location without assigning aberrant ER retention of pathogenic variants as a wild-type core function. |
| GO:0097233 alveolar lamellar body membrane | IDA PMID:11940594 Identification of LBM180, a lamellar body limiting membrane ... | ACCEPT | Summary: The limiting membrane of alveolar lamellar bodies is the main physiological site of ABCA3. Reason: PMID:11940594 identifies the lamellar-body limiting-membrane antigen LBM180 as ABCA3 by immunoprecipitation and mass spectrometry and reports its targeting to vesicle membranes. This directly supports the alveolar lamellar-body membrane location. |
| GO:0097233 alveolar lamellar body membrane | IDA PMID:16959783 Characterization and classification of ATP-binding cassette ... | ACCEPT | Summary: The limiting membrane of alveolar lamellar bodies is the main physiological site of ABCA3. Reason: PMID:16959783 contrasts wild-type ABCA3 trafficking to LAMP3-positive intracellular vesicles with ER retention of type I disease mutants in HEK293 cells. This model-cell evidence corroborates the native alveolar lamellar-body membrane location independently established by PMID:11940594; mutant ER retention does not redefine the wild-type physiological compartment. |
| GO:0097233 alveolar lamellar body membrane | IEA GO_REF:0000120 | ACCEPT | Summary: The limiting membrane of alveolar lamellar bodies is the main physiological site of ABCA3. Reason: GO_REF:0000120 agrees with human microscopy (PMID:11718719; PMID:11940594) and ABCA3 maturation/localization (PMID:20863830). Retain the location without assigning aberrant ER retention of pathogenic variants as a wild-type core function. Propagation Review Root cause: NO FAILURE CORE Sources checked: UniProtKB:A0A0G2K1Q8 SUPPORTS TRANSFER Recorded mammalian localization donor is consistent with native human ABCA3 immunoelectron microscopy at the alveolar lamellar-body limiting membrane (PMID:11718719; PMID:11940594). ensembl:ENSRNOP00000071944 SUPPORTS TRANSFER Recorded mammalian localization donor is consistent with native human ABCA3 immunoelectron microscopy at the alveolar lamellar-body limiting membrane (PMID:11718719; PMID:11940594). UniProtKB:Q8R420 SUPPORTS TRANSFER Recorded mammalian localization donor is consistent with native human ABCA3 immunoelectron microscopy at the alveolar lamellar-body limiting membrane (PMID:11718719; PMID:11940594). ensembl:ENSMUSP00000078544 SUPPORTS TRANSFER Recorded mammalian localization donor is consistent with native human ABCA3 immunoelectron microscopy at the alveolar lamellar-body limiting membrane (PMID:11718719; PMID:11940594). |
| GO:0120019 phosphatidylcholine transfer activity | IMP PMID:28887056 Quantification of volume and lipid filling of intracellular ... | MODIFY | Summary: ABCA3 mediates ATP-dependent membrane translocation of phosphatidylcholine, not an aqueous-phase transfer shuttle. Reason: The live GO:0120019 definition requires removal from a membrane and protected passage through an aqueous phase to an acceptor. The accessible full text of PMID:28887056 instead measures TopFluor-PC loading into membrane-bound ABCA3-positive vesicles, and PMID:35394827 resolves an integral membrane ABC transporter. Replace the transfer-shuttle mechanism with the existing ATPase-coupled intramembrane lipid-carrier activity. Proposed replacements: ATPase-coupled intramembrane lipid transporter activity |
| GO:0140326 ATPase-coupled intramembrane lipid carrier activity | EXP PMID:17574245 ABCA3-mediated choline-phospholipids uptake into intracellul... | ACCEPT | Summary: ATP-coupled intramembrane lipid transport is the core ABCA3 molecular activity. Reason: PMID:17574245 supports the established ABCA3 transporter mechanism. Human cell assays demonstrate ATP-dependent phospholipid vesicle loading and variant-dependent impairment; the structure/ATPase study supports lateral lipid access and ATP-driven extrusion. Exact substrate preference and leaflet-resolved kinetics remain less certain than this encompassing activity. The structural paper proposes the transport cycle and does not itself perform a purified lipid-flux assay. Supporting Evidence: PMID:17574245 ABCA3 mediates ATP-dependent choline-phospholipids uptake into intracellular vesicles. file:human/ABCA3/ABCA3-deep-research-falcon.md Its principal physiological function is to load surfactant phospholipids |
| GO:0140326 ATPase-coupled intramembrane lipid carrier activity | EXP PMID:27177387 Tools to explore ABCA3 mutations causing interstitial lung d... | ACCEPT | Summary: ATP-coupled intramembrane lipid transport is the core ABCA3 molecular activity. Reason: PMID:27177387 supports the established ABCA3 transporter mechanism. Human cell assays demonstrate ATP-dependent phospholipid vesicle loading and variant-dependent impairment; the structure/ATPase study supports lateral lipid access and ATP-driven extrusion. Exact substrate preference and leaflet-resolved kinetics remain less certain than this encompassing activity. The structural paper proposes the transport cycle and does not itself perform a purified lipid-flux assay. |
| GO:0140326 ATPase-coupled intramembrane lipid carrier activity | EXP PMID:28887056 Quantification of volume and lipid filling of intracellular ... | ACCEPT | Summary: ATP-coupled intramembrane lipid transport is the core ABCA3 molecular activity. Reason: PMID:28887056 supports the established ABCA3 transporter mechanism. Human cell assays demonstrate ATP-dependent phospholipid vesicle loading and variant-dependent impairment; the structure/ATPase study supports lateral lipid access and ATP-driven extrusion. Exact substrate preference and leaflet-resolved kinetics remain less certain than this encompassing activity. The structural paper proposes the transport cycle and does not itself perform a purified lipid-flux assay. |
| GO:0140326 ATPase-coupled intramembrane lipid carrier activity | EXP PMID:31473345 Metabolic labelling of choline phospholipids probes ABCA3 tr... | ACCEPT | Summary: ATP-coupled intramembrane lipid transport is the core ABCA3 molecular activity. Reason: PMID:31473345 supports the established ABCA3 transporter mechanism. Human cell assays demonstrate ATP-dependent phospholipid vesicle loading and variant-dependent impairment; the structure/ATPase study supports lateral lipid access and ATP-driven extrusion. Exact substrate preference and leaflet-resolved kinetics remain less certain than this encompassing activity. The structural paper proposes the transport cycle and does not itself perform a purified lipid-flux assay. |
| GO:0140326 ATPase-coupled intramembrane lipid carrier activity | IEA GO_REF:0000003 | ACCEPT | Summary: ATP-coupled intramembrane lipid transport is the core ABCA3 molecular activity. Reason: GO_REF:0000003 supports the established ABCA3 transporter mechanism. Human cell assays demonstrate ATP-dependent phospholipid vesicle loading and variant-dependent impairment; the structure/ATPase study supports lateral lipid access and ATP-driven extrusion. Exact substrate preference and leaflet-resolved kinetics remain less certain than this encompassing activity. The structural paper proposes the transport cycle and does not itself perform a purified lipid-flux assay. Propagation Review Root cause: NO FAILURE CORE Sources checked: EC:7.6.2.1 SUPPORTS TRANSFER The recorded source is compatible with the human ABCA3 transport mechanism or localization, corroborated by the primary studies cited in this review. |
| GO:0140345 phosphatidylcholine flippase activity | IMP PMID:27177387 Tools to explore ABCA3 mutations causing interstitial lung d... | MODIFY | Summary: The phosphatidylcholine transport evidence does not support the flippase direction specified by this GO term. Reason: Live QuickGO defines GO:0140345 as exoplasmic-to-cytosolic phosphatidylcholine movement. ABCA3 cellular studies measure delivery into lamellar-body-like vesicles, and PMID:35394827 proposes the opposite, cytosolic-to-luminal export model. These data do not resolve leaflet-specific flux directly. Replace with GO:0140326, preserving ATP-coupled lipid transport without asserting the incorrect directional term or promoting a structural model to a direct floppase assay. Proposed replacements: ATPase-coupled intramembrane lipid transporter activity |
| GO:0140345 phosphatidylcholine flippase activity | IMP PMID:31473345 Metabolic labelling of choline phospholipids probes ABCA3 tr... | MODIFY | Summary: The phosphatidylcholine transport evidence does not support the flippase direction specified by this GO term. Reason: Live QuickGO defines GO:0140345 as exoplasmic-to-cytosolic phosphatidylcholine movement. ABCA3 cellular studies measure delivery into lamellar-body-like vesicles, and PMID:35394827 proposes the opposite, cytosolic-to-luminal export model. These data do not resolve leaflet-specific flux directly. Replace with GO:0140326, preserving ATP-coupled lipid transport without asserting the incorrect directional term or promoting a structural model to a direct floppase assay. Proposed replacements: ATPase-coupled intramembrane lipid transporter activity |
| GO:0140359 ABC-type transporter activity | IEA GO_REF:0000002 | ACCEPT | Summary: ABCA3 is a functional ABC-type transporter. Reason: The ABCA/transmembrane-domain mappings are supported by the human ATP-bound structure, biochemical ATPase activity and phospholipid-loading assays. The generic family molecular function remains valid; the core synthesis uses the lipid-specific term already in this annotation set. Propagation Review Root cause: NO FAILURE CORE Sources checked: InterPro:IPR013525 SUPPORTS TRANSFER The recorded ABCA/ABC nucleotide-binding or transmembrane feature agrees with the experimentally resolved human transporter architecture. InterPro:IPR026082 SUPPORTS TRANSFER The recorded ABCA/ABC nucleotide-binding or transmembrane feature agrees with the experimentally resolved human transporter architecture. |
| GO:0150172 regulation of phosphatidylcholine metabolic process | IMP PMID:25817392 ABCA3 protects alveolar epithelial cells against free choles... | UNDECIDED | Summary: The specific phosphatidylcholine-metabolism regulatory annotation needs the source experiments. Reason: PMID:25817392 establishes free-cholesterol changes, SREBP activation and protection from cholesterol toxicity in the accessible abstract. Phospholipids were measured, but the specific phosphatidylcholine regulatory mechanism cannot be resolved from that abstract, and the full text was not recovered. Do not infer that the curator lacked additional evidence or substitute a cholesterol result for this distinct process. |
| GO:0150172 regulation of phosphatidylcholine metabolic process | IMP PMID:31473345 Metabolic labelling of choline phospholipids probes ABCA3 tr... | MODIFY | Summary: Metabolic labeling is used to assay ABCA3 transport rather than establish ABCA3 as a regulator of phosphatidylcholine synthesis. Reason: PMID:31473345 separates early choline-kinase-dependent label incorporation from later vesicular accumulation, and reports reduced intravesicular but unchanged extravesicular lipid signal in ABCA3 mutants. The measured ABCA3 activity is transport of labeled phospholipids into vesicles. Replace the regulatory-metabolism process with phospholipid transport; choline kinase and other biosynthetic enzymes perform the chemical labeling reactions. Proposed replacements: phospholipid transport |
| GO:1902995 positive regulation of phospholipid efflux | IMP PMID:31473345 Metabolic labelling of choline phospholipids probes ABCA3 tr... | MODIFY | Summary: ABCA3 directly transports phospholipids into its organelle rather than merely increasing another transporter activity. Reason: The cited variant/vesicle assays and independent human transport studies support ABCA3 as the ATP-dependent lipid-moving enzyme. The direct process is phospholipid transport. Regulatory wording obscures that role, and vesicle loading should not be described as ABCA3 directly controlling lamellar-body exocytosis or cell-surface phospholipid release. Proposed replacements: phospholipid transport |
| GO:2001140 positive regulation of phospholipid transport | IMP PMID:27177387 Tools to explore ABCA3 mutations causing interstitial lung d... | MODIFY | Summary: ABCA3 directly transports phospholipids into its organelle rather than merely increasing another transporter activity. Reason: The cited variant/vesicle assays and independent human transport studies support ABCA3 as the ATP-dependent lipid-moving enzyme. The direct process is phospholipid transport. Regulatory wording obscures that role, and vesicle loading should not be described as ABCA3 directly controlling lamellar-body exocytosis or cell-surface phospholipid release. Proposed replacements: phospholipid transport |
Loading supporting content…
Download this section (compressed HTML)Q: Does purified, oriented ABCA3 directly flop phosphatidylcholine from the cytosolic to the luminal leaflet, and what are its kinetic preferences for PC, PG, sphingomyelin and cholesterol?
Q: What experiment in the rat donor source PMID:15904872 supports ABCA3 positive regulation of vesicle fusion, and is the function separable from lipid loading?
Q: Which supplemental observations support the human ABCA3 vesicle-membrane annotation in PMID:22673903 and the minority plasma-membrane location in PMID:11718719?
Q: Does oligomerization alter native ABCA3 transport, or primarily track correct folding and trafficking?
Experiment: Reconstitute purified ABCA3 into oriented proteoliposomes and measure ATP-dependent, leaflet-resolved flux of defined labeled PC and PG species alongside ATPase-deficient controls. This would test GO:0090554 directionality independently of organelle biogenesis and nonspecific vanadate effects.
Experiment: Combine endogenous ABCA3 oligomer-state measurements with lipid-flux assays in gene-corrected human alveolar type II models, controlling for protein abundance and organelle trafficking.
Loading supporting content…
Download this section (compressed HTML)Loading supporting content…
Download this section (compressed HTML)Loading supporting content…
Download this section (compressed HTML)