ATP1A3

Summary: The IPR023299-derived nucleotide-binding inference agrees with the nucleotide-binding domain of human alpha3.

Reason: The IPR023299-derived nucleotide-binding inference agrees with the nucleotide-binding domain of human alpha3. PMID:36075933 reports an AMPPCP-bound E1•ATP-like structural state and independent ATP-dependent phosphorylation and hydrolysis assays. Retain this broad property without a redundant replacement.

Summary: Human alpha3 directly binds synthetic amylospheroids in the original PMID:26224839 Results (human SPR Kd 28.6 nM).

Reason: Human alpha3 directly binds synthetic amylospheroids in the original PMID:26224839 Results (human SPR Kd 28.6 nM). This is a pathological ligand interaction, separate from the normal Na/K transport core; rat neuron toxicity assays are not human neuronal experiments.

Summary: The review-linked amyloid binding assertion is independently supported by direct human-protein SPR in PMID:26224839.

Reason: The review-linked amyloid binding assertion is independently supported by direct human-protein SPR in PMID:26224839. The complete PMID:26871627 abstract was read, but its full target-specific discussion was not; retain TAS and do not present that review as a new direct assay.

Summary: Photoreceptor inner-segment localization is compatible with the pump active compartment and the curated orthology transfer.

Reason: Photoreceptor inner-segment localization is compatible with the pump active compartment and the curated orthology transfer. PMID:26373354 directly localizes Xenopus alpha3 in inner-segment plasma membrane; this corroborates the location class without converting the mouse ISS donor into human IDA.

Summary: Human alpha3 combined with each human beta isoform generated K-activated pump currents in Xenopus oocytes in PMID:10636900.

Reason: Human alpha3 combined with each human beta isoform generated K-activated pump currents in Xenopus oocytes in PMID:10636900. The expressed protein is human even though the assay host is frog; this directly supports coupled Na/K transport.

Summary: Human alpha3/beta1/FXYD6 expressed in HEK293F supports whole-cell pump current, purified ATP turnover and Na/K-bound structures in PMID:36075933.

Reason: Human alpha3/beta1/FXYD6 expressed in HEK293F supports whole-cell pump current, purified ATP turnover and Na/K-bound structures in PMID:36075933. This is the catalytic molecular function and is the preferred core anchor.

Summary: The EC/Rhea/ARBA pump mapping agrees with the directly measured human alpha3 Na/K pump activity in PMID:36075933 and PMID:10636900.

Reason: The EC/Rhea/ARBA pump mapping agrees with the directly measured human alpha3 Na/K pump activity in PMID:36075933 and PMID:10636900. No loss of catalytic function in the normal human target is indicated.

Summary: PMID:15260953 reports human ATP1A3 disease variants with impaired enzyme activity or stability.

Reason: PMID:15260953 reports human ATP1A3 disease variants with impaired enzyme activity or stability. Preserve the original IMP assertion; the normal human pump function is independently established by direct functional studies, while the full original mutant panels were not inspected here.

Summary: PMID:26224839 measures alpha3-associated pump inhibition and its biological consequences.

Reason: PMID:26224839 measures alpha3-associated pump inhibition and its biological consequences. Its NAS assertion agrees with independent direct human pump assays; do not upgrade its evidence code or treat the rat neuronal assay as human IDA.

Summary: The curated PMID:32814053 candidate interaction with UniProtKB:P12757 is also listed in the immutable UniProt record.

Reason: The curated PMID:32814053 candidate interaction with UniProtKB:P12757 is also listed in the immutable UniProt record. The exact target-pair assay, construct and confirmation table were not inspected. Preserve the source and defer this interaction; an uninspected pair is not refuted, and verified generic binding would be non-core.

Summary: The curated PMID:32814053 candidate interaction with UniProtKB:P15923-3 is also listed in the immutable UniProt record.

Reason: The curated PMID:32814053 candidate interaction with UniProtKB:P15923-3 is also listed in the immutable UniProt record. The exact target-pair assay, construct and confirmation table were not inspected. Preserve the source and defer this interaction; an uninspected pair is not refuted, and verified generic binding would be non-core.

Summary: The curated PMID:32814053 candidate interaction with UniProtKB:P17024 is also listed in the immutable UniProt record.

Reason: The curated PMID:32814053 candidate interaction with UniProtKB:P17024 is also listed in the immutable UniProt record. The exact target-pair assay, construct and confirmation table were not inspected. Preserve the source and defer this interaction; an uninspected pair is not refuted, and verified generic binding would be non-core.

Summary: The curated PMID:32814053 candidate interaction with UniProtKB:Q08AE8 is also listed in the immutable UniProt record.

Reason: The curated PMID:32814053 candidate interaction with UniProtKB:Q08AE8 is also listed in the immutable UniProt record. The exact target-pair assay, construct and confirmation table were not inspected. Preserve the source and defer this interaction; an uninspected pair is not refuted, and verified generic binding would be non-core.

Summary: The curated PMID:32814053 candidate interaction with UniProtKB:Q08AM6 is also listed in the immutable UniProt record.

Reason: The curated PMID:32814053 candidate interaction with UniProtKB:Q08AM6 is also listed in the immutable UniProt record. The exact target-pair assay, construct and confirmation table were not inspected. Preserve the source and defer this interaction; an uninspected pair is not refuted, and verified generic binding would be non-core.

Summary: The curated PMID:32814053 candidate interaction with UniProtKB:Q0VD86 is also listed in the immutable UniProt record.

Reason: The curated PMID:32814053 candidate interaction with UniProtKB:Q0VD86 is also listed in the immutable UniProt record. The exact target-pair assay, construct and confirmation table were not inspected. Preserve the source and defer this interaction; an uninspected pair is not refuted, and verified generic binding would be non-core.

Summary: The curated PMID:32814053 candidate interaction with UniProtKB:Q12888 is also listed in the immutable UniProt record.

Reason: The curated PMID:32814053 candidate interaction with UniProtKB:Q12888 is also listed in the immutable UniProt record. The exact target-pair assay, construct and confirmation table were not inspected. Preserve the source and defer this interaction; an uninspected pair is not refuted, and verified generic binding would be non-core.

Summary: The curated PMID:32814053 candidate interaction with UniProtKB:Q6NXG1 is also listed in the immutable UniProt record.

Reason: The curated PMID:32814053 candidate interaction with UniProtKB:Q6NXG1 is also listed in the immutable UniProt record. The exact target-pair assay, construct and confirmation table were not inspected. Preserve the source and defer this interaction; an uninspected pair is not refuted, and verified generic binding would be non-core.

Summary: The curated PMID:32814053 candidate interaction with UniProtKB:Q6XD76 is also listed in the immutable UniProt record.

Reason: The curated PMID:32814053 candidate interaction with UniProtKB:Q6XD76 is also listed in the immutable UniProt record. The exact target-pair assay, construct and confirmation table were not inspected. Preserve the source and defer this interaction; an uninspected pair is not refuted, and verified generic binding would be non-core.

Summary: The curated PMID:32814053 candidate interaction with UniProtKB:Q6ZQX7-4 is also listed in the immutable UniProt record.

Reason: The curated PMID:32814053 candidate interaction with UniProtKB:Q6ZQX7-4 is also listed in the immutable UniProt record. The exact target-pair assay, construct and confirmation table were not inspected. Preserve the source and defer this interaction; an uninspected pair is not refuted, and verified generic binding would be non-core.

Summary: The curated PMID:32814053 candidate interaction with UniProtKB:Q6ZSB9 is also listed in the immutable UniProt record.

Reason: The curated PMID:32814053 candidate interaction with UniProtKB:Q6ZSB9 is also listed in the immutable UniProt record. The exact target-pair assay, construct and confirmation table were not inspected. Preserve the source and defer this interaction; an uninspected pair is not refuted, and verified generic binding would be non-core.

Summary: The curated PMID:32814053 candidate interaction with UniProtKB:Q96PV4 is also listed in the immutable UniProt record.

Reason: The curated PMID:32814053 candidate interaction with UniProtKB:Q96PV4 is also listed in the immutable UniProt record. The exact target-pair assay, construct and confirmation table were not inspected. Preserve the source and defer this interaction; an uninspected pair is not refuted, and verified generic binding would be non-core.

Summary: The curated PMID:32814053 candidate interaction with UniProtKB:Q99504 is also listed in the immutable UniProt record.

Reason: The curated PMID:32814053 candidate interaction with UniProtKB:Q99504 is also listed in the immutable UniProt record. The exact target-pair assay, construct and confirmation table were not inspected. Preserve the source and defer this interaction; an uninspected pair is not refuted, and verified generic binding would be non-core.

Summary: The curated PMID:32814053 candidate interaction with UniProtKB:Q9GZQ6 is also listed in the immutable UniProt record.

Reason: The curated PMID:32814053 candidate interaction with UniProtKB:Q9GZQ6 is also listed in the immutable UniProt record. The exact target-pair assay, construct and confirmation table were not inspected. Preserve the source and defer this interaction; an uninspected pair is not refuted, and verified generic binding would be non-core.

Summary: The curated PMID:32814053 candidate interaction with UniProtKB:Q9H7C4 is also listed in the immutable UniProt record.

Reason: The curated PMID:32814053 candidate interaction with UniProtKB:Q9H7C4 is also listed in the immutable UniProt record. The exact target-pair assay, construct and confirmation table were not inspected. Preserve the source and defer this interaction; an uninspected pair is not refuted, and verified generic binding would be non-core.

Summary: The curated PMID:32814053 candidate interaction with UniProtKB:Q9UMX3 is also listed in the immutable UniProt record.

Reason: The curated PMID:32814053 candidate interaction with UniProtKB:Q9UMX3 is also listed in the immutable UniProt record. The exact target-pair assay, construct and confirmation table were not inspected. Preserve the source and defer this interaction; an uninspected pair is not refuted, and verified generic binding would be non-core.

Summary: The curated PMID:32814053 candidate interaction with UniProtKB:Q9UQM7 is also listed in the immutable UniProt record.

Reason: The curated PMID:32814053 candidate interaction with UniProtKB:Q9UQM7 is also listed in the immutable UniProt record. The exact target-pair assay, construct and confirmation table were not inspected. Preserve the source and defer this interaction; an uninspected pair is not refuted, and verified generic binding would be non-core.

Summary: The InterPro IPR001757/IPR005775 ATP-binding inference is consistent with the alpha3 catalytic domain.

Reason: The InterPro IPR001757/IPR005775 ATP-binding inference is consistent with the alpha3 catalytic domain. Human alpha3 ATP-dependent phosphorylation and hydrolysis assays in PMID:36075933 corroborate ATP use; its E1•ATP-like structure contains the ATP analogue AMPPCP. This is part of the coupled transport core.

Summary: The original PMID:15260953 NAS ATP-binding assertion is consistent with the ATP-driven pump mechanism, although the original full variant panels were not inspected.

Reason: The original PMID:15260953 NAS ATP-binding assertion is consistent with the ATP-driven pump mechanism, although the original full variant panels were not inspected. Independent human alpha3 ATP-dependent phosphorylation and hydrolysis in PMID:36075933 corroborate the activity; its AMPPCP-bound structural state is not described as chemically bound ATP.

Summary: Endoplasmic-reticulum residence is plausible during pump biosynthesis, but the cited PMID:15260953 localization panel was not accessible in this reading.

Reason: Endoplasmic-reticulum residence is plausible during pump biosynthesis, but the cited PMID:15260953 localization panel was not accessible in this reading. Wild-type residence versus disease-variant retention cannot be resolved from its abstract, so preserve the IDA row pending that panel.

Summary: Golgi transit of alpha/beta complexes is supported generally by maturation experiments, but the exact PMID:15260953 Golgi localization panel and wild-type-versus-mutant context were not inspected.

Reason: Golgi transit of alpha/beta complexes is supported generally by maturation experiments, but the exact PMID:15260953 Golgi localization panel and wild-type-versus-mutant context were not inspected. Do not infer a stable Golgi role from trafficking plausibility; retain the source row undecided.

Summary: Plasma membrane is the active site of the conserved electrogenic pump.

Reason: Plasma membrane is the active site of the conserved electrogenic pump. Direct human surface/current measurements support the target itself; the self-containing PAINT evidence list is legitimate descendant grounding, not circularity, and there is no target-specific loss argument.

Summary: Plasma-membrane localization is independently demonstrated for human alpha3 in PMID:36075933 and human cardiomyocytes in PMID:19751721.

Reason: Plasma-membrane localization is independently demonstrated for human alpha3 in PMID:36075933 and human cardiomyocytes in PMID:19751721. Preserve the original PMID:15260953 IDA attribution while disclosing that its original localization panel was not freshly read.

Summary: PMID:36075933 combines whole-cell pump currents and surface-biotinylation analysis of the human alpha3/beta1/FXYD6 complex in HEK293F.

Reason: PMID:36075933 combines whole-cell pump currents and surface-biotinylation analysis of the human alpha3/beta1/FXYD6 complex in HEK293F. These target-specific observations support the plasma-membrane location.

Summary: The UniProt subcellular-location mapping to plasma membrane agrees with direct human alpha3 current and surface-localization evidence.

Reason: The UniProt subcellular-location mapping to plasma membrane agrees with direct human alpha3 current and surface-localization evidence. Keep the correct broad electronic assertion unchanged.

Summary: PMID:19751721 expresses human alpha3/beta1 in yeast and separately immunolocalizes endogenous alpha3 in isolated human atrial cardiomyocytes.

Reason: PMID:19751721 expresses human alpha3/beta1 in yeast and separately immunolocalizes endogenous alpha3 in isolated human atrial cardiomyocytes. Alpha3 occurs at plasma and intracellular membranes, but not the T tubules seen for alpha1/alpha2; preserve the original IGI/beta1 source qualifier.

Summary: The complete R-HSA-936897 summary describes sodium-potassium exchange by the plasma-membrane ATP1A:ATP1B:FXYD complex.

Reason: The complete R-HSA-936897 summary describes sodium-potassium exchange by the plasma-membrane ATP1A:ATP1B:FXYD complex. This pathway placement agrees with direct human alpha3 localization and transport; no separate signaling activity is inferred.

Summary: The complete R-HSA-9684068 summary describes cardiac-glycoside binding to the plasma-membrane ATP1A:ATP1B:FXYD complex.

Reason: The complete R-HSA-9684068 summary describes cardiac-glycoside binding to the plasma-membrane ATP1A:ATP1B:FXYD complex. Retain the location TAS assertion, independently corroborated by human alpha3 surface measurements, without treating pathway membership as a new signaling function.

Summary: Alpha3 is the catalytic subunit of the sodium:potassium-exchanging ATPase complex.

Reason: Alpha3 is the catalytic subunit of the sodium:potassium-exchanging ATPase complex. The IC inference from its pump activity agrees with the directly assembled human alpha3/beta1/FXYD6 complex; retain the original IC source.

Summary: PMID:10636900 original pulse-chase and non-denaturing immunoprecipitation Results show human alpha3 coassembly with human beta1, beta2 and beta3 in oocytes.

Reason: PMID:10636900 original pulse-chase and non-denaturing immunoprecipitation Results show human alpha3 coassembly with human beta1, beta2 and beta3 in oocytes. This supports complex membership; exact stoichiometry quantified for alpha1 is not silently transferred to alpha3.

Summary: The ARBA00088151 complex-membership inference agrees with direct assembly of human alpha3 with beta subunits in PMID:10636900 and the alpha3/beta1/FXYD6 preparation in PMID:36075933.

Reason: The ARBA00088151 complex-membership inference agrees with direct assembly of human alpha3 with beta subunits in PMID:10636900 and the alpha3/beta1/FXYD6 preparation in PMID:36075933. It does not imply that alpha3 alone forms the complete pump.

Summary: The original PMID:26224839 NAS complex-membership assertion is consistent with alpha3 being the catalytic subunit of the sodium-potassium pump.

Reason: The original PMID:26224839 NAS complex-membership assertion is consistent with alpha3 being the catalytic subunit of the sodium-potassium pump. Direct human alpha3/beta-subunit assembly in PMID:10636900 and the alpha3/beta1/FXYD6 complex in PMID:36075933 provide independent corroboration without upgrading the NAS evidence code.

Summary: Potassium transport is an essential component of the coupled pump cycle and is experimentally corroborated.

Reason: Potassium transport is an essential component of the coupled pump cycle and is experimentally corroborated. Its broad InterPro-derived process term is correct; the existing more specific import rows already provide precision.

Summary: Conserved intracellular sodium homeostasis follows from the alpha3 sodium-export cycle and is grounded in direct target experiments.

Reason: Conserved intracellular sodium homeostasis follows from the alpha3 sodium-export cycle and is grounded in direct target experiments. The PAINT assertion is a phylogenetic judgment; target self-evidence and donor count provide no basis to reject it.

Summary: PMID:10636900 measures human alpha3 pump-current activation by intracellular sodium in oocytes.

Reason: PMID:10636900 measures human alpha3 pump-current activation by intracellular sodium in oocytes. Coupled sodium extrusion directly maintains the intracellular sodium gradient, supporting the homeostatic process.

Summary: The ARBA sodium-homeostasis inference is consistent with direct alpha3 sodium transport.

Reason: The ARBA sodium-homeostasis inference is consistent with direct alpha3 sodium transport. This is a core consequence of the catalytic step performed by the target, not merely a disease phenotype.

Summary: P-type potassium transport is a valid broader molecular-function assertion for the Na/K-exchanging pump.

Reason: P-type potassium transport is a valid broader molecular-function assertion for the Na/K-exchanging pump. It does not establish potassium-only or H/K pumping; retain it alongside the already existing specific exchange function.

Summary: The electrogenic pump itself transfers cations against their gradients, directly establishing the transmembrane electrochemical gradient.

Reason: The electrogenic pump itself transfers cations against their gradients, directly establishing the transmembrane electrochemical gradient. This GO-to-GO inference is mechanistically supported and does not require an additional NEW process.

Summary: The InterPro IPR001757/IPR005775 membrane-location mapping agrees with the multipass alpha3 topology and human surface-biotinylation/current measurements in PMID:36075933.

Reason: The InterPro IPR001757/IPR005775 membrane-location mapping agrees with the multipass alpha3 topology and human surface-biotinylation/current measurements in PMID:36075933. Retain this correct broad location alongside the existing plasma-membrane assertions.

Summary: The curated UniProtKB:P06687 donor-based ISS membrane-location assertion is consistent with conserved pump topology and direct human alpha3 membrane measurements.

Reason: The curated UniProtKB:P06687 donor-based ISS membrane-location assertion is consistent with conserved pump topology and direct human alpha3 membrane measurements. Preserve its orthology provenance rather than converting it to human IDA or assigning a narrower compartment from the donor alone.

Summary: The original PMID:15260953 NAS membrane-location assertion is consistent with alpha3 pump topology.

Reason: The original PMID:15260953 NAS membrane-location assertion is consistent with alpha3 pump topology. Independent human surface measurements in PMID:36075933 and cardiomyocyte localization in PMID:19751721 corroborate this broad location, while the original ER/Golgi panels remain uninspected.

Summary: Purified human alpha3/beta1/FXYD6 hydrolyzes ATP in the PMID:36075933 biochemical assay.

Reason: Purified human alpha3/beta1/FXYD6 hydrolyzes ATP in the PMID:36075933 biochemical assay. Retain this broad activity as part of the coupled pump mechanism, without creating a second independent ATPase core.

Summary: Intracellular potassium homeostasis is the conserved result of the pump potassium-import step.

Reason: Intracellular potassium homeostasis is the conserved result of the pump potassium-import step. Direct human transport supports the phylogenetic assertion; there is no target-specific divergence argument.

Summary: External potassium activation of currents in human alpha3-containing oocyte pumps in PMID:10636900 supports potassium uptake and homeostasis.

Reason: External potassium activation of currents in human alpha3-containing oocyte pumps in PMID:10636900 supports potassium uptake and homeostasis. Preserve the human-protein/frog-host distinction and original IDA provenance.

Summary: The ARBA potassium-homeostasis assertion agrees with direct alpha3 pump function.

Reason: The ARBA potassium-homeostasis assertion agrees with direct alpha3 pump function. It represents the target catalytic contribution to maintaining ion gradients.

Summary: PMID:26224839 includes alpha3 neuronal/neuropil labeling and human cortical axonal staining, alongside rat neuronal assays.

Reason: PMID:26224839 includes alpha3 neuronal/neuropil labeling and human cortical axonal staining, alongside rat neuronal assays. Retain axon localization with these species and tissue scopes; it does not imply all human neuronal perturbation assays were performed.

Summary: Alpha3 is a neuronal surface pump, and PMID:26224839 contains cell-body and surface-labeling evidence.

Reason: Alpha3 is a neuronal surface pump, and PMID:26224839 contains cell-body and surface-labeling evidence. Preserve the original IC location inference; intracellular somatic staining in the same work is not all assigned to surface membrane.

Summary: Sodium export across plasma membrane is the conserved direction of the alpha3 Na/K pump cycle.

Reason: Sodium export across plasma membrane is the conserved direction of the alpha3 Na/K pump cycle. Direct target activity supports the PAINT inference, whose source list should not be treated as a pairwise similarity score.

Summary: Human alpha3-containing pumps produce K-activated electrogenic currents with intracellular sodium dependence in PMID:10636900.

Reason: Human alpha3-containing pumps produce K-activated electrogenic currents with intracellular sodium dependence in PMID:10636900. This supports sodium export; retain the original IDA source without inventing a separate tracer assay.

Summary: The ARBA sodium-export mapping is consistent with the directly established pump cycle and plasma-membrane location.

Reason: The ARBA sodium-export mapping is consistent with the directly established pump cycle and plasma-membrane location. The gene performs the transport step itself.

Summary: Original PMID:26224839 human cortical staining includes pyramidal cell bodies, and rat neuronal labeling provides complementary context.

Reason: Original PMID:26224839 human cortical staining includes pyramidal cell bodies, and rat neuronal labeling provides complementary context. Keep cell-body localization while distinguishing punctate surface/neuropil labeling from diffuse intracellular signal.

Summary: Synaptic localization by orthology is consistent with the neuronal pump distribution and existing human neuropil/axon observations.

Reason: Synaptic localization by orthology is consistent with the neuronal pump distribution and existing human neuropil/axon observations. Keep the ISS assertion with its donor provenance; this is not a newly demonstrated human postsynaptic binding interaction.

Summary: The chaperone-binding class is consistent with beta-subunit-mediated alpha3 assembly, stabilization and trafficking.

Reason: The chaperone-binding class is consistent with beta-subunit-mediated alpha3 assembly, stabilization and trafficking. GO0051087 includes binding proteins that ensure folding or transport; it does not claim that alpha3 itself is a folding chaperone. Keep the electronic binding assertion outside the transport core.

Summary: PMID:10636900 original Results show human alpha3 coassembly with human beta1 and protection from degradation in the oocyte pulse-chase experiment.

Reason: PMID:10636900 original Results show human alpha3 coassembly with human beta1 and protection from degradation in the oocyte pulse-chase experiment. This supports binding to a partner with assembly/trafficking chaperone function under GO0051087, not autonomous chaperone activity by alpha3; keep the pair non-core.

Summary: PMID:10636900 original Results show human alpha3 coassembly with human beta2 and protection from degradation in the oocyte pulse-chase experiment.

Reason: PMID:10636900 original Results show human alpha3 coassembly with human beta2 and protection from degradation in the oocyte pulse-chase experiment. This supports binding to a partner with assembly/trafficking chaperone function under GO0051087, not autonomous chaperone activity by alpha3; keep the pair non-core.

Summary: PMID:10636900 original Results show human alpha3 coassembly with human beta3 and protection from degradation in the oocyte pulse-chase experiment.

Reason: PMID:10636900 original Results show human alpha3 coassembly with human beta3 and protection from degradation in the oocyte pulse-chase experiment. This supports binding to a partner with assembly/trafficking chaperone function under GO0051087, not autonomous chaperone activity by alpha3; keep the pair non-core.

Summary: The electrogenic alpha3 pump contributes to resting membrane potential by sustaining Na/K gradients.

Reason: The electrogenic alpha3 pump contributes to resting membrane potential by sustaining Na/K gradients. PMID:26224839 reports sodium accumulation and depolarization when alpha3 is inhibited in rat neurons; keep TAS and the rat functional context while recognizing the conserved human pump mechanism.

Summary: PMID:26373354 Methods explicitly use GFP-tagged Xenopus laevis alpha3 in transgenic Xenopus rods; the human construct in that study is alpha4.

Reason: PMID:26373354 Methods explicitly use GFP-tagged Xenopus laevis alpha3 in transgenic Xenopus rods; the human construct in that study is alpha4. The observed inner-segment plasma-membrane targeting supports the original orthology-based ISS assertion, not human IDA or alpha4 outer-segment placement.

Summary: The broad steroid-hormone response is retained as non-core pharmacological context, with the chemical classification and cellular endpoint recorded separately.

Reason: Official ChEBI explicitly asserts CHEBI:472805 (ouabain) is_a CHEBI:26764 (steroid hormone); the latter has_role CHEBI:24621 (hormone). This is the documented ontology classification, not an inference that every steroid is a hormone. GO:0071383 covers a change in cellular state or activity after this class of stimulus. The original PMID:11546672 remains a binding-focused NAS source. Separately inspected original PMID:10636900 Methods and Fig. 6 measure currents before and after 100 micromolar ouabain in intact Xenopus oocytes expressing human alpha3/beta1, with uninjected currents subtracted. This functional endpoint supports the broad response term at that experimental scope. Retention does not assert physiological hormone concentrations, native-human endocrine signaling, or a steroid-hormone receptor transcriptional pathway. ChEBI and GO relationship URLs and the access date are recorded in the notes.

Summary: GO0086064 specifically requires current transfer between adjacent cell cytoplasms through intercellular channels.

Reason: GO0086064 specifically requires current transfer between adjacent cell cytoplasms through intercellular channels. Alpha3 maintains ionic gradients, but the inspected cardiac evidence concerns pump abundance, contractility and calcium transients rather than that intercellular coupling step. The ARBA propagation is too specific; this does not deny a role in excitability.

Summary: The selected original PMID:19683723 Methods/Results use mouse ventricular beta1 deletion, pump ATPase, contractility and calcium-transient assays; human alpha3 appears in clinical discussion.

Reason: The selected original PMID:19683723 Methods/Results use mouse ventricular beta1 deletion, pump ATPase, contractility and calcium-transient assays; human alpha3 appears in clinical discussion. These do not establish the adjacent-cell channel-current transfer required by GO0086064. Mark the process specificity excessive, without claiming misidentification or absence of any cardiac alpha3 role.

Summary: The mouse-to-human neuronal-synapse location inference is compatible with the conserved neuronal alpha3 pump and independent neuronal surface distribution.

Reason: The mouse-to-human neuronal-synapse location inference is compatible with the conserved neuronal alpha3 pump and independent neuronal surface distribution. Preserve ISS and avoid upgrading it to a human synapse-subtype assay.

Summary: Human alpha3-containing pumps have measured ouabain-dependent activity changes, supporting a non-core response to a glycoside.

Reason: Ouabain is_a cardenolide glycoside (CHEBI:472805 -> CHEBI:38092) in ChEBI. The original PMID:11546672 remains a binding-focused NAS source. Additional PMID:10636900 reports human alpha/beta pumps in Xenopus oocytes and isoform-specific K(+)/ouabain pharmacology in its cached abstract. Previously inspected original Methods and Fig. 6 measure alpha3/beta1-dependent current before and after ouabain with uninjected currents subtracted. These functional measurements support a non-core glycoside-response context. This reason does not require ouabain to act at a physiological endocrine concentration.

Summary: Detected in an extracellular-vesicle proteome. The protein is plausible EV content, but this is not where it functions.

Reason: Plasma-membrane Na+/K+-ATPase. Transmembrane/lipid-anchored protein of the plasma membrane or endosomal system (UniProt); such proteins are expected EV contents (MISEV2018 (PMID:30637094) category 1). True, but not its core location. (Manual re-review for OMICS_EVIDENCE, 2026-10-10; previous action: UNDECIDED.)

Summary: The curated rat-to-human amyloid-response assertion is consistent with alpha3 inhibition and ensuing ionic disruption in the original rat neuronal experiments.

Reason: The curated rat-to-human amyloid-response assertion is consistent with alpha3 inhibition and ensuing ionic disruption in the original rat neuronal experiments. Retain it as pathological context, distinct from human direct SPR binding and from the normal transport core.

Summary: Human alpha3-containing pumps bind ouabain, supported by PMID:11546672 and human isoform studies.

Reason: Human alpha3-containing pumps bind ouabain, supported by PMID:11546672 and human isoform studies. Official ChEBI explicitly asserts ouabain (CHEBI:472805) is_a steroid hormone (CHEBI:26764). Retain this ligand-binding function as non-core pharmacological context without inferring that alpha3 is a steroid-hormone transcription factor or that the assays establish a physiological endocrine role. Binding evidence and the separately assessed cellular-response evidence are distinct.

Summary: The original amyloid study links alpha3 depletion/inhibition to neuronal survival and neurite disruption, with most perturbation experiments in rat cultures.

Reason: The original amyloid study links alpha3 depletion/inhibition to neuronal survival and neurite disruption, with most perturbation experiments in rat cultures. Preserve the curated IGI/APP source as a contextual maintenance assertion, without turning pump necessity into a new process or assigning direct APP processing.

Summary: Potassium import across plasma membrane is the conserved second ion-transfer component of the alpha3 pump.

Reason: Potassium import across plasma membrane is the conserved second ion-transfer component of the alpha3 pump. The target has direct functional grounding for the PAINT assertion; preserve the original phylogenetic provenance.

Summary: PMID:10636900 demonstrates external-potassium activation of human alpha3 pump currents.

Reason: PMID:10636900 demonstrates external-potassium activation of human alpha3 pump currents. This supports the potassium-import component of the established pump cycle without inventing a separately read isotope-flux assay.

Summary: The ARBA potassium-import mapping agrees with directly established human Na/K exchange.

Reason: The ARBA potassium-import mapping agrees with directly established human Na/K exchange. Existing specific transport terms already cover the core, so no NEW process is needed.