Ankyrin-B is a membrane-associated adaptor that binds spectrins and organizes ion channels, transporters and other membrane proteins. In cardiac cells it positions calcium-handling proteins and supports electrical activity; in muscle it contributes to dystrophin-associated membrane organization. A 220-kDa form also couples PI3P-bearing organelles to dynactin and recruits RabGAP1L during endosomal trafficking. The giant neuronal form contains an insertion that binds and bundles microtubules to constrain axonal branching. It also maintains L1CAM-neuropilin receptor complexes at the neuronal surface for Sema3A responses, through a mechanism separable from its microtubule-binding and betaII-spectrin interactions.
| GO Term | Evidence | Action | Reason |
|---|---|---|---|
| GO:0002027 regulation of heart rate | IMP PMID:18832177 Dysfunction in ankyrin-B-dependent ion channel and transport... | ACCEPT | Summary: Ankyrin-B-dependent channel organization regulates cardiac pacemaking. Reason: The PMID:18832177 abstract explicitly links human ANK2 variants to sinus-node disease and reports abnormal pacing and ion-channel organization in deficient mice. This is a supported physiological consequence of the cardiac membrane adaptor mechanism, without attributing pacemaker-channel conductance to ANK2. |
| GO:0003283 atrial septum development | IMP PMID:18832177 Dysfunction in ankyrin-B-dependent ion channel and transport... | UNDECIDED | Summary: The atrial-septum developmental experiment is not exposed in the accessible source. Reason: PMID:18832177 is cached as an abstract about sinus-node dysfunction. Its full developmental experiments were not inspected. A clinical arrhythmia phenotype does not itself establish atrial septum development, but incomplete access is not grounds to overturn the experimental curator. |
| GO:0005200 structural constituent of cytoskeleton | IEA GO_REF:0000107 | ACCEPT | Summary: Ankyrin-B provides structural links within the membrane-associated cytoskeleton. Reason: The rat orthology assertion is consistent with direct ANK2 spectrin binding and membrane-target organization. Human/mammalian cardiac and muscle experiments establish the structural adaptor role independently of the unreconstructed historical Ensembl donor record. Propagation Review Root cause: NO FAILURE CORE Sources checked: UniProtKB:F1M5N3 UNRESOLVED Original source identifier preserved. The exact historical source assertion/construct was not independently reconstructed; target-level primary corroboration or uncertainty is stated in the row reason. ensembl:ENSRNOP00000035307 UNRESOLVED Original source identifier preserved. The exact historical source assertion/construct was not independently reconstructed; target-level primary corroboration or uncertainty is stated in the row reason. Supporting Evidence: PMID:15262991 Therefore, direct binding of beta(2)-spectrin to ankyrin-B is required for the normal targeting of beta(2)-spectrin in neonatal cardiomyocytes. |
| GO:0005515 protein binding | IPI PMID:15262991 Ankyrin-B targets beta2-spectrin to an intracellular compart... | MODIFY | Summary: The demonstrated interaction is specifically with beta2-spectrin. Reason: PMID:15262991 names beta2-spectrin and shows that loss of ankyrin-B spectrin-binding activity prevents beta2-spectrin targeting. Refine generic binding to the existing spectrin-binding activity; preserve original Q01082 partner provenance. Proposed replacements: spectrin binding Supporting Evidence: PMID:15262991 Therefore, direct binding of beta(2)-spectrin to ankyrin-B is required for the normal targeting of beta(2)-spectrin in neonatal cardiomyocytes. |
| GO:0005515 protein binding | IPI PMID:15611082 The ammonium transporter RhBG: requirement of a tyrosine-bas... | UNDECIDED | Summary: The source-specific ANK2βRhBG interaction requires the original full experiment. Reason: PMID:15611082 describes ankyrin-G and human RhBG in canine MDCK cells in its accessible abstract. The full article may include ankyrin-B tests, and was not inspected. Do not remove this experimental ANK2βQ9H310 assertion because the title foregrounds another ankyrin; the exact pair and construct remain unresolved. |
| GO:0005515 protein binding | IPI PMID:17178715 Targeting and stability of Na/Ca exchanger 1 in cardiomyocyt... | MODIFY | Summary: NCX1 binding is a membrane-transporter interaction. Reason: PMID:17178715 directly identifies NCX1 binding and a required ankyrin-B binding motif for targeting/stability in cardiomyocytes. P32418 is the source NCX1 partner. Refine to the seeded transporter-binding function, without converting ankyrin-B into an exchanger. Proposed replacements: transmembrane transporter binding Supporting Evidence: PMID:17178715 we demonstrate that direct interaction with the membrane adaptor ankyrin-B is required for the localization and post-translational stability of Na/Ca exchanger 1 in neonatal mouse cardiomyocytes. |
| GO:0005515 protein binding | IPI PMID:17474147 Systematic identification of SH3 domain-mediated human prote... | UNDECIDED | Summary: The exact ANK2βGRB2 interaction record is unavailable. Reason: The abstract of PMID:17474147 describes a broad SH3 peptide-array survey with validation of a subset of interactions. It does not expose the ANK2βP62993 pair, tested fragment or pair-specific validation. Generic binding is uninformative, but inaccessible experimental pair data must not be blindly removed. |
| GO:0005515 protein binding | IPI PMID:19109891 An ankyrin-based mechanism for functional organization of dy... | MODIFY | Summary: The dystrophin interaction supports a cytoskeletal adaptor mechanism. Reason: PMID:19109891 distinguishes ankyrin-B-dependent dystrophin transport to the sarcolemma from ankyrin-G-dependent retention. The original dystrophin isoform P11532-5 remains unchanged. The functional assembly/transport context supports cytoskeletal adaptor activity more informatively than generic binding; it does not make the two ankyrins interchangeable. Proposed replacements: cytoskeletal adaptor activity Supporting Evidence: PMID:19109891 Ankyrin-B thus is an adaptor required for sarcolemmal localization of dystrophin, as well as dynactin-4. |
| GO:0005515 protein binding | IPI PMID:19805355 Dual role of K ATP channel C-terminal motif in membrane targ... | MODIFY | Summary: Kir6.2 is a directly bound membrane-channel target. Reason: PMID:19805355 identifies a Kir6.2 C-terminal ankyrin-B-binding motif required for channel targeting and metabolic regulation. The source partner Q14654 is retained. The specific transporter-binding term captures the demonstrated interaction without assuming a particular direction of channel gating. Proposed replacements: transmembrane transporter binding |
| GO:0005515 protein binding | IPI PMID:20489164 EH domain proteins regulate cardiac membrane protein targeti... | UNDECIDED | Summary: EHD3 is relevant to targeting, but the precise binding mechanism remains unresolved. Reason: The canonical PMID:20489164 record is abstract-only. It reports EHD1β4 interaction with ankyrin-B and EHD3-dependent targeting; a longer recovered candidate was inspected only in part and was not substituted for the canonical record. Exact Q9NZN3 pair constructs and a more informative functional interaction term remain unsettled, so retain experimental uncertainty. |
| GO:0005515 protein binding | IPI PMID:21859974 Defects in ankyrin-based membrane protein targeting pathways... | MODIFY | Summary: Cav1.3 association is specifically membrane-transporter binding. Reason: Full PMID:21859974 maps the ankyrin-B interaction to the Cav1.3 C-terminal region and connects it to membrane localization/current. The original Q99246 partner is mouse Cacna1d, not a human accession. Refine the generic binding assertion while preserving that species-specific source object. Proposed replacements: transmembrane transporter binding |
| GO:0005515 protein binding | IPI PMID:26949739 Identification of Human Neuronal Protein Complexes Reveals B... | REMOVE | Summary: The ACOT7 association is real but generic protein binding is not a functional annotation. Reason: Relevant full PMID:26949739 Results explicitly confirm ACOT7 in ANK2-purified lysates by targeted co-immunoprecipitation in differentiated SH-SY5Y cells. Thus this is not a wrong-gene or missing-pair rejection. The association does not establish a specific ANK2 biochemical function with ACOT7, and generic protein binding adds no functional content; no acyl-CoA-metabolic role is inferred. |
| GO:0005515 protein binding | IPI PMID:30021884 Histone Interaction Landscapes Visualized by Crosslinking Ma... | UNDECIDED | Summary: The ANK2βRRBP1 pair cannot be checked in the partial extraction. Reason: Although PMID:30021884 has full_text_available true, the actual canonical body contains only Abstract and Discussion. Its ANK2βQ9P2E9 pair data and experimental details are absent from the inspected extract. Do not treat this partial source or the paper title as sufficient grounds to remove an experimental assertion. |
| GO:0005515 protein binding | IPI PMID:32353364 Structural Basis Underlying Strong Interactions between Anky... | MODIFY | Summary: The structural partner is beta4-spectrin. Reason: The PMID:32353364 abstract reports ankyrinβspectrin complex structures. Independently inspected primary PDB entry 6M3Q identifies human ANK2/Q01484 with mouse Sptbn4/E9PX29. Refine generic binding to spectrin binding; the partner species is kept explicit and full article inspection is not claimed. Proposed replacements: spectrin binding |
| GO:0005515 protein binding | IPI PMID:36950384 Protein interaction studies in human induced neurons indicat... | UNDECIDED | Summary: The exact interaction pair requires supplementary record inspection. Reason: Relevant main sections of PMID:36950384 describe native human induced-neuron IP-MS and giant-ANK2 perturbation. The original ANK2 partner assertion is preserved, but the pair-specific supplementary tables and direct-versus-complex-mediated interaction evidence were not inspected. Main-body network statements do not justify either a specific replacement function or removal of this experimental pair. |
| GO:0005515 protein binding | IPI PMID:36950384 Protein interaction studies in human induced neurons indicat... | UNDECIDED | Summary: The exact interaction pair requires supplementary record inspection. Reason: Relevant main sections of PMID:36950384 describe native human induced-neuron IP-MS and giant-ANK2 perturbation. The original ANK2 partner assertion is preserved, but the pair-specific supplementary tables and direct-versus-complex-mediated interaction evidence were not inspected. Main-body network statements do not justify either a specific replacement function or removal of this experimental pair. |
| GO:0005737 cytoplasm | IEA GO_REF:0000117 | ACCEPT | Summary: Ankyrin-B occupies the cytoplasm as a peripheral membrane/cytoskeletal adaptor. Reason: The ARBA assertion is broad and consistent with direct intracellular cardiac ankyrin-B localization and its cytosolic membrane-target binding machinery. Independent primary evidence supports the conclusion even though the exact historical ARBA rule was not reconstructed. Propagation Review Root cause: NO FAILURE CORE Sources checked: ARBA:ARBA00026971 UNRESOLVED Original source identifier preserved. The exact historical source assertion/construct was not independently reconstructed; target-level primary corroboration or uncertainty is stated in the row reason. |
| GO:0005739 mitochondrion | IEA GO_REF:0000044 | ACCEPT | Summary: A restricted mitochondrial-associated ankyrin-B pool is experimentally supported. Reason: The full normal PMID:27718357 record reports 220-kDa AnkB-mCherry puncta at mitochondrial ends in mouse embryonic fibroblasts. PMID:25533844 independently reports cotransport and restricted mitochondrial contact points in mouse hippocampal neurons. These data support the broad organelle-associated location in the original UniProt/mouse transfer, without implying matrix residence, uniform mitochondrial coating, or localization of every isoform. Propagation Review Root cause: NO FAILURE CORE Sources checked: UniProtKB-SubCell:SL-0173 UNRESOLVED Original source identifier preserved. The exact historical source assertion/construct was not independently reconstructed; target-level primary corroboration or uncertainty is stated in the row reason. Supporting Evidence: PMID:27718357 Moreover, we detected a restrictedΒ association of AnkB-mCherry with puncta at mitochondria ends. |
| GO:0005739 mitochondrion | ISS GO_REF:0000024 | ACCEPT | Summary: A restricted mitochondrial-associated ankyrin-B pool is experimentally supported. Reason: The full normal PMID:27718357 record reports 220-kDa AnkB-mCherry puncta at mitochondrial ends in mouse embryonic fibroblasts. PMID:25533844 independently reports cotransport and restricted mitochondrial contact points in mouse hippocampal neurons. These data support the broad organelle-associated location in the original UniProt/mouse transfer, without implying matrix residence, uniform mitochondrial coating, or localization of every isoform. Propagation Review Root cause: NO FAILURE CORE Sources checked: UniProtKB:Q8C8R3 UNRESOLVED Original source identifier preserved. The exact historical source assertion/construct was not independently reconstructed; target-level primary corroboration or uncertainty is stated in the row reason. Supporting Evidence: PMID:27718357 Moreover, we detected a restrictedΒ association of AnkB-mCherry with puncta at mitochondria ends. |
| GO:0005764 lysosome | IEA GO_REF:0000044 | ACCEPT | Summary: A lysosome-associated ankyrin-B pool is experimentally supported. Reason: PMID:27718357 directly reports partial overlap of 220-kDa AnkB-mCherry with LAMP1-positive lysosomes in mouse embryonic fibroblasts; PMID:25533844 independently detects associated/cotransported LAMP1 cargoes in mouse hippocampal axons. Accept the existing location with this tested context. Lack of lysosome colocalization in neonatal cardiac cells does not universally exclude this pool. Propagation Review Root cause: NO FAILURE CORE Sources checked: UniProtKB-SubCell:SL-0158 UNRESOLVED Original source identifier preserved. The exact historical source assertion/construct was not independently reconstructed; target-level primary corroboration or uncertainty is stated in the row reason. Supporting Evidence: PMID:27718357 Although WT AnkB-mCherry expressed was preferentially localized to Rab5-positive early endosomes, it also exhibited partial overlap with Rab11-positive recycling endosomes and LAMP1-positive lysosomes. |
| GO:0005764 lysosome | ISS GO_REF:0000024 | ACCEPT | Summary: A lysosome-associated ankyrin-B pool is experimentally supported. Reason: PMID:27718357 directly reports partial overlap of 220-kDa AnkB-mCherry with LAMP1-positive lysosomes in mouse embryonic fibroblasts; PMID:25533844 independently detects associated/cotransported LAMP1 cargoes in mouse hippocampal axons. Accept the existing location with this tested context. Lack of lysosome colocalization in neonatal cardiac cells does not universally exclude this pool. Propagation Review Root cause: NO FAILURE CORE Sources checked: UniProtKB:Q8C8R3 UNRESOLVED Original source identifier preserved. The exact historical source assertion/construct was not independently reconstructed; target-level primary corroboration or uncertainty is stated in the row reason. Supporting Evidence: PMID:27718357 Although WT AnkB-mCherry expressed was preferentially localized to Rab5-positive early endosomes, it also exhibited partial overlap with Rab11-positive recycling endosomes and LAMP1-positive lysosomes. |
| GO:0005769 early endosome | IEA GO_REF:0000044 | ACCEPT | Summary: Early-endosomal ankyrin-B localization is directly supported. Reason: PMID:27718357 directly reports preferential 220-kDa AnkB-mCherry localization to Rab5-positive early endosomes in mouse embryonic fibroblasts, with a PI3P-binding mutant losing organelle localization. PMID:25533844 supplies independent neuronal Rab5-cargo evidence. This corroborates the original UniProt/mouse location assertions; it does not assign RabGAP catalysis to ankyrin-B. Propagation Review Root cause: NO FAILURE CORE Sources checked: UniProtKB-SubCell:SL-0094 UNRESOLVED Original source identifier preserved. The exact historical source assertion/construct was not independently reconstructed; target-level primary corroboration or uncertainty is stated in the row reason. Supporting Evidence: PMID:27718357 Although WT AnkB-mCherry expressed was preferentially localized to Rab5-positive early endosomes, it also exhibited partial overlap with Rab11-positive recycling endosomes and LAMP1-positive lysosomes. |
| GO:0005769 early endosome | ISS GO_REF:0000024 | ACCEPT | Summary: Early-endosomal ankyrin-B localization is directly supported. Reason: PMID:27718357 directly reports preferential 220-kDa AnkB-mCherry localization to Rab5-positive early endosomes in mouse embryonic fibroblasts, with a PI3P-binding mutant losing organelle localization. PMID:25533844 supplies independent neuronal Rab5-cargo evidence. This corroborates the original UniProt/mouse location assertions; it does not assign RabGAP catalysis to ankyrin-B. Propagation Review Root cause: NO FAILURE CORE Sources checked: UniProtKB:Q8C8R3 UNRESOLVED Original source identifier preserved. The exact historical source assertion/construct was not independently reconstructed; target-level primary corroboration or uncertainty is stated in the row reason. Supporting Evidence: PMID:27718357 Although WT AnkB-mCherry expressed was preferentially localized to Rab5-positive early endosomes, it also exhibited partial overlap with Rab11-positive recycling endosomes and LAMP1-positive lysosomes. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-392751 | ACCEPT | Summary: A cytosolic ankyrin-B pool is consistent with membrane-trafficking adaptor activity. Reason: The cited normal Reactome summary was inspected and places ankyrin-associated trafficking machinery in a cytosolic reaction context. Retain only the cytosol location asserted by this row. The surrounding coat, ARF, tethering or SNARE reaction does not assign its catalytic activity to ankyrin-B; independent cardiac intracellular localization corroborates the broad location. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-445076 | ACCEPT | Summary: A cytosolic ankyrin-B pool is consistent with membrane-trafficking adaptor activity. Reason: The cited normal Reactome summary was inspected and places ankyrin-associated trafficking machinery in a cytosolic reaction context. Retain only the cytosol location asserted by this row. The surrounding coat, ARF, tethering or SNARE reaction does not assign its catalytic activity to ankyrin-B; independent cardiac intracellular localization corroborates the broad location. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-6807875 | ACCEPT | Summary: A cytosolic ankyrin-B pool is consistent with membrane-trafficking adaptor activity. Reason: The cited normal Reactome summary was inspected and places ankyrin-associated trafficking machinery in a cytosolic reaction context. Retain only the cytosol location asserted by this row. The surrounding coat, ARF, tethering or SNARE reaction does not assign its catalytic activity to ankyrin-B; independent cardiac intracellular localization corroborates the broad location. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-6807877 | ACCEPT | Summary: A cytosolic ankyrin-B pool is consistent with membrane-trafficking adaptor activity. Reason: The cited normal Reactome summary was inspected and places ankyrin-associated trafficking machinery in a cytosolic reaction context. Retain only the cytosol location asserted by this row. The surrounding coat, ARF, tethering or SNARE reaction does not assign its catalytic activity to ankyrin-B; independent cardiac intracellular localization corroborates the broad location. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-6809003 | ACCEPT | Summary: A cytosolic ankyrin-B pool is consistent with membrane-trafficking adaptor activity. Reason: The cited normal Reactome summary was inspected and places ankyrin-associated trafficking machinery in a cytosolic reaction context. Retain only the cytosol location asserted by this row. The surrounding coat, ARF, tethering or SNARE reaction does not assign its catalytic activity to ankyrin-B; independent cardiac intracellular localization corroborates the broad location. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-6809006 | ACCEPT | Summary: A cytosolic ankyrin-B pool is consistent with membrane-trafficking adaptor activity. Reason: The cited normal Reactome summary was inspected and places ankyrin-associated trafficking machinery in a cytosolic reaction context. Retain only the cytosol location asserted by this row. The surrounding coat, ARF, tethering or SNARE reaction does not assign its catalytic activity to ankyrin-B; independent cardiac intracellular localization corroborates the broad location. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-6809010 | ACCEPT | Summary: A cytosolic ankyrin-B pool is consistent with membrane-trafficking adaptor activity. Reason: The cited normal Reactome summary was inspected and places ankyrin-associated trafficking machinery in a cytosolic reaction context. Retain only the cytosol location asserted by this row. The surrounding coat, ARF, tethering or SNARE reaction does not assign its catalytic activity to ankyrin-B; independent cardiac intracellular localization corroborates the broad location. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-6809011 | ACCEPT | Summary: A cytosolic ankyrin-B pool is consistent with membrane-trafficking adaptor activity. Reason: The cited normal Reactome summary was inspected and places ankyrin-associated trafficking machinery in a cytosolic reaction context. Retain only the cytosol location asserted by this row. The surrounding coat, ARF, tethering or SNARE reaction does not assign its catalytic activity to ankyrin-B; independent cardiac intracellular localization corroborates the broad location. |
| GO:0005856 cytoskeleton | IEA GO_REF:0000044 | ACCEPT | Summary: Ankyrin-B associates with the membrane cytoskeleton. Reason: The UniProt subcellular-location mapping agrees with direct spectrin binding and cardiac/muscle scaffold localization. The broad cytoskeleton term is accurate and does not assert that ankyrin-B catalyzes filament polymerization. Propagation Review Root cause: NO FAILURE CORE Sources checked: UniProtKB-SubCell:SL-0090 UNRESOLVED Original source identifier preserved. The exact historical source assertion/construct was not independently reconstructed; target-level primary corroboration or uncertainty is stated in the row reason. Supporting Evidence: PMID:15262991 Therefore, direct binding of beta(2)-spectrin to ankyrin-B is required for the normal targeting of beta(2)-spectrin in neonatal cardiomyocytes. |
| GO:0005886 plasma membrane | EXP PMID:19007774 Ankyrin-B is required for coordinated expression of beta-2-s... | ACCEPT | Summary: Rod inner-segment ankyrin-B is membrane associated. Reason: The PMID:19007774 abstract explicitly examines rod photoreceptors from humans, mice and frogs and places ankyrin-B with Na/K-ATPase and Na/Ca exchanger at the inner segment. This supports the broader plasma-membrane annotation without moving the protein to the outer segment. |
| GO:0005886 plasma membrane | IBA GO_REF:0000033 | ACCEPT | Summary: Plasma-membrane anchoring is a conserved ankyrin-B function. Reason: The actual cached PAINT table contains GO:0005886 IBD at PTN002380879, supported in part by human ANK2 descendant evidence. Self-inclusion is legitimate experimental grounding. Direct target localization independently supports the term; no loss/divergence or contrary node placement is demonstrated. Full tree/MSA reconstruction is not claimed. Propagation Review Root cause: NO FAILURE CORE Sources checked: FB:FBgn0011747 UNRESOLVED Original source identifier preserved. The exact historical source assertion/construct was not independently reconstructed; target-level primary corroboration or uncertainty is stated in the row reason. PANTHER:PTN002380879 SUPPORTS TRANSFER Actual PTHR24123 PAINT table contains the matching IBD at PTN002380879. Full tree/MSA and all historical descendant experiments were not reconstructed. RGD:1309620 UNRESOLVED Original source identifier preserved. The exact historical source assertion/construct was not independently reconstructed; target-level primary corroboration or uncertainty is stated in the row reason. UniProtKB:P16157 UNRESOLVED Original source identifier preserved. The exact historical source assertion/construct was not independently reconstructed; target-level primary corroboration or uncertainty is stated in the row reason. UniProtKB:Q01484 SUPPORTS TRANSFER ANK2 is itself an experimentally grounded descendant source for the ancestral-node inference; this is valid PAINT provenance, not circularity. UniProtKB:Q12955 UNRESOLVED Original source identifier preserved. The exact historical source assertion/construct was not independently reconstructed; target-level primary corroboration or uncertainty is stated in the row reason. |
| GO:0005886 plasma membrane | IDA GO_REF:0000052 | ACCEPT | Summary: Plasma-membrane localization is corroborated by independent target evidence. Reason: The source is curated immunofluorescence under GO_REF:0000052. The exact historical HPA image was not re-opened, but human/mammalian rod and cardiac targeting evidence independently establishes the same broad location. Accept the supported biological conclusion without claiming fresh image-level validation. |
| GO:0005886 plasma membrane | IEA GO_REF:0000044 | ACCEPT | Summary: Ankyrin-B acts at the cytoplasmic face of the plasma membrane. Reason: The source location/ortholog/literature assertion is consistent with direct membrane-transporter binding and localization in cardiac and rod cells. Ankyrin-B is a peripheral cytoplasmic adaptor rather than an integral membrane transporter. The broad localization is supported independently of every historical source detail. Propagation Review Root cause: NO FAILURE CORE Sources checked: UniProtKB-SubCell:SL-0039 UNRESOLVED Original source identifier preserved. The exact historical source assertion/construct was not independently reconstructed; target-level primary corroboration or uncertainty is stated in the row reason. |
| GO:0005886 plasma membrane | ISS GO_REF:0000024 | ACCEPT | Summary: Ankyrin-B acts at the cytoplasmic face of the plasma membrane. Reason: The source location/ortholog/literature assertion is consistent with direct membrane-transporter binding and localization in cardiac and rod cells. Ankyrin-B is a peripheral cytoplasmic adaptor rather than an integral membrane transporter. The broad localization is supported independently of every historical source detail. Propagation Review Root cause: NO FAILURE CORE Sources checked: UniProtKB:Q8C8R3 UNRESOLVED Original source identifier preserved. The exact historical source assertion/construct was not independently reconstructed; target-level primary corroboration or uncertainty is stated in the row reason. |
| GO:0005886 plasma membrane | NAS PMID:17178715 Targeting and stability of Na/Ca exchanger 1 in cardiomyocyt... | ACCEPT | Summary: Ankyrin-B acts at the cytoplasmic face of the plasma membrane. Reason: The source location/ortholog/literature assertion is consistent with direct membrane-transporter binding and localization in cardiac and rod cells. Ankyrin-B is a peripheral cytoplasmic adaptor rather than an integral membrane transporter. The broad localization is supported independently of every historical source detail. Supporting Evidence: PMID:17178715 we demonstrate that direct interaction with the membrane adaptor ankyrin-B is required for the localization and post-translational stability of Na/Ca exchanger 1 in neonatal mouse cardiomyocytes. |
| GO:0006874 intracellular calcium ion homeostasis | ISS GO_REF:0000024 | ACCEPT | Summary: Cardiac membrane-target organization contributes to intracellular calcium homeostasis. Reason: Human ankyrin-B constructs rescue calcium-handling and transporter-positioning defects in mouse cardiomyocytes in full PMID:15178757. Retain this established physiological consequence of the adaptor mechanism; ANK2 itself does not transport calcium. Propagation Review Root cause: NO FAILURE CORE Sources checked: UniProtKB:Q8C8R3 UNRESOLVED Original source identifier preserved. The exact historical source assertion/construct was not independently reconstructed; target-level primary corroboration or uncertainty is stated in the row reason. |
| GO:0007010 cytoskeleton organization | IEA GO_REF:0000108 | ACCEPT | Summary: Ankyrin-B organizes selected membrane-associated cytoskeletal assemblies. Reason: The broad logical inference is independently supported by beta2-spectrin targeting and dystrophin-associated organization. This does not claim every cytoskeletal assembly or neuronal periodic ring requires ankyrin-B. Propagation Review Root cause: NO FAILURE CORE Sources checked: GO:0005200 UNRESOLVED Original source identifier preserved. The exact historical source assertion/construct was not independently reconstructed; target-level primary corroboration or uncertainty is stated in the row reason. Supporting Evidence: PMID:15262991 Therefore, direct binding of beta(2)-spectrin to ankyrin-B is required for the normal targeting of beta(2)-spectrin in neonatal cardiomyocytes. |
| GO:0007165 signal transduction | IEA GO_REF:0000002 | KEEP AS NON CORE | Summary: Ankyrin-B can organize signaling proteins, but the death-domain signature alone is nonspecific. Reason: IPR000488 is a death-domain mapping, not proof of a particular receptor/death signaling pathway. The experimentally supported M-line ankyrin-BβobscurinβPP2A organization supplies a contextual signaling connection. Retain the broad process as non-core rather than translating a domain label into a new signaling mechanism. Propagation Review Root cause: NO FAILURE NON CORE Sources checked: InterPro:IPR000488 UNRESOLVED Original source identifier preserved. The exact historical source assertion/construct was not independently reconstructed; target-level primary corroboration or uncertainty is stated in the row reason. |
| GO:0007399 nervous system development | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Giant ankyrin-B contributes to axon architecture and guidance during nervous-system development. Reason: The now-read giant-isoform studies establish direct microtubule binding and suppression of ectopic axon branching, alongside a distinct Sema3A receptor-organizing mechanism in mouse neurons. These mechanisms corroborate the broad nervous-system developmental context beyond disease association alone. Retain the existing rat-derived assertion as non-core, while preserving uncertainty about the exact historical Ensembl/UniProt donor experiment; that unreconstructed provenance does not negate independent target-gene evidence. Propagation Review Root cause: UNRESOLVED Sources checked: UniProtKB:F1M5N3 UNRESOLVED Original source identifier preserved. The exact historical source assertion/construct was not independently reconstructed; target-level primary corroboration or uncertainty is stated in the row reason. ensembl:ENSRNOP00000035307 UNRESOLVED Original source identifier preserved. The exact historical source assertion/construct was not independently reconstructed; target-level primary corroboration or uncertainty is stated in the row reason. Supporting Evidence: PMID:32640013 Taken together, gAnkB contains a stretch of amino acids (1793β2070) that avidly bind and bundle MTs in vitro. |
| GO:0008093 cytoskeletal adaptor activity | IBA GO_REF:0000033 | ACCEPT | Summary: Ankyrin-B is a cytoskeletal adaptor. Reason: The actual cached PAINT IBD at PTN002380879 assigns cytoskeletal adaptor activity, with human ANK1 experimental descendant grounding. A single donor is not weak support by itself. Independent ANK2 spectrin, transporter and muscle-scaffold experiments directly corroborate the same molecular role; no contrary clade placement is established. Propagation Review Root cause: NO FAILURE CORE Sources checked: PANTHER:PTN002380879 SUPPORTS TRANSFER Actual PTHR24123 PAINT table contains the matching IBD at PTN002380879. Full tree/MSA and all historical descendant experiments were not reconstructed. UniProtKB:P16157 UNRESOLVED Original source identifier preserved. The exact historical source assertion/construct was not independently reconstructed; target-level primary corroboration or uncertainty is stated in the row reason. Supporting Evidence: PMID:15262991 Therefore, direct binding of beta(2)-spectrin to ankyrin-B is required for the normal targeting of beta(2)-spectrin in neonatal cardiomyocytes. |
| GO:0008104 intracellular protein localization | IGI PMID:15262991 Ankyrin-B targets beta2-spectrin to an intracellular compart... | ACCEPT | Summary: Ankyrin-B positions beta2-spectrin inside cardiomyocytes. Reason: PMID:15262991 directly reports loss of beta2-spectrin localization in ankyrin-B-null cardiomyocytes and rescue by wild-type ankyrin-B, with spectrin-binding mutants separating this targeting function from other activities. This is structural participation in protein positioning, not a phenotype-only developmental inference. Propagation Review Root cause: NO FAILURE CORE Sources checked: UniProtKB:Q8C8R3 UNRESOLVED Original source identifier preserved. The exact historical source assertion/construct was not independently reconstructed; target-level primary corroboration or uncertainty is stated in the row reason. Supporting Evidence: PMID:15262991 Therefore, direct binding of beta(2)-spectrin to ankyrin-B is required for the normal targeting of beta(2)-spectrin in neonatal cardiomyocytes. |
| GO:0008104 intracellular protein localization | IGI PMID:17242276 Defining the cellular phenotype of "ankyrin-B syndrome" vari... | ACCEPT | Summary: Ankyrin-B-dependent intracellular protein positioning is supported. Reason: PMID:17242276 reports variant-dependent cellular targeting defects, although the canonical source is abstract-only. Full independent PMID:15178757 shows rescue of NCX, Na/K-ATPase and IP3R organization by human ankyrin-B constructs in mouse cardiomyocytes. Accept the general localization process without claiming all source-specific variant assays were reread. Propagation Review Root cause: NO FAILURE CORE Sources checked: UniProtKB:Q8C8R3 UNRESOLVED Original source identifier preserved. The exact historical source assertion/construct was not independently reconstructed; target-level primary corroboration or uncertainty is stated in the row reason. |
| GO:0010628 positive regulation of gene expression | IGI PMID:17242276 Defining the cellular phenotype of "ankyrin-B syndrome" vari... | UNDECIDED | Summary: The gene-expression mechanism is not resolved by protein-level rescue. Reason: PMID:17242276 is available as an abstract. Changes in mature membrane-protein abundance can result from targeting and stability, whereas GO:0010628 denotes increased gene-expression biosynthesis. The original full experiments were not inspected, so do not assert that transcription/translation assays were absent or remove the experimental annotation on that assumption. Propagation Review Root cause: UNRESOLVED Sources checked: UniProtKB:Q8C8R3 UNRESOLVED Original source identifier preserved. The exact historical source assertion/construct was not independently reconstructed; target-level primary corroboration or uncertainty is stated in the row reason. |
| GO:0010881 regulation of cardiac muscle contraction by regulation of the release of sequestered calcium ion | IGI PMID:17178715 Targeting and stability of Na/Ca exchanger 1 in cardiomyocyt... | UNDECIDED | Summary: The precise sequestered-calcium-release mechanism is not exposed by this source abstract. Reason: PMID:17178715 directly supports NCX1 binding, membrane targeting and posttranslational stability. NCX1 transport at the plasma membrane is distinct from sarcoplasmic-reticulum calcium release. The full original experiments may contain relevant downstream measurements, so preserve uncertainty for this narrower experimental process. Propagation Review Root cause: UNRESOLVED Sources checked: UniProtKB:Q8C8R3 UNRESOLVED Original source identifier preserved. The exact historical source assertion/construct was not independently reconstructed; target-level primary corroboration or uncertainty is stated in the row reason. |
| GO:0010881 regulation of cardiac muscle contraction by regulation of the release of sequestered calcium ion | ISS PMID:21859974 Defects in ankyrin-based membrane protein targeting pathways... | MODIFY | Summary: The inspected source supports regulation of calcium transport through channel targeting. Reason: Full PMID:21859974 maps Cav1.3 binding and membrane-targeting defects and measures atrial calcium currents. Those experiments do not directly establish regulation through release from a sequestered calcium store. Refine this source-specific claim to the existing general calcium-transport regulation term and consolidate with its other supported rows, without discarding the observed cardiac phenotype. Propagation Review Root cause: UNRESOLVED Sources checked: UniProtKB:Q8C8R3 UNRESOLVED Original source identifier preserved. The exact historical source assertion/construct was not independently reconstructed; target-level primary corroboration or uncertainty is stated in the row reason. Proposed replacements: regulation of calcium ion transport |
| GO:0010882 regulation of cardiac muscle contraction by calcium ion signaling | IMP PMID:12571597 Ankyrin-B mutation causes type 4 long-QT cardiac arrhythmia ... | ACCEPT | Summary: Ankyrin-B regulates cardiac contraction through organized calcium-handling machinery. Reason: The PMID:12571597 abstract explicitly reports disrupted targeting of Na/K-ATPase, NCX and IP3 receptors and altered calcium signaling in deficient cardiomyocytes. Full PMID:15178757 corroborates human-protein rescue of calcium and contraction phenotypes. This is regulation through an adaptor mechanism, not calcium-channel catalysis. |
| GO:0014704 intercalated disc | ISS GO_REF:0000024 | UNDECIDED | Summary: The intercalated-disc pool needs its specific ortholog experiment checked. Reason: The mouse-orthology source is retained, but the direct ANK2 experiment supporting this precise membrane subdomain was not recovered. Cardiac membrane localization alone does not determine intercalated-disc localization. Familiar ankyrin-G biology is not evidence of ANK2 misattribution. Propagation Review Root cause: UNRESOLVED Sources checked: UniProtKB:Q8C8R3 UNRESOLVED Original source identifier preserved. The exact historical source assertion/construct was not independently reconstructed; target-level primary corroboration or uncertainty is stated in the row reason. |
| GO:0016020 membrane | EXP PMID:19007774 Ankyrin-B is required for coordinated expression of beta-2-s... | ACCEPT | Summary: Ankyrin-B is a membrane-associated peripheral adaptor. Reason: The broad membrane location is supported by the human/mouse/frog rod inner-segment study and cardiac membrane-transporter targeting. It is accurate despite the more specific plasma-membrane rows and does not imply a transmembrane segment. |
| GO:0016020 membrane | IEA GO_REF:0000044 | ACCEPT | Summary: Ankyrin-B is a membrane-associated peripheral adaptor. Reason: The broad membrane location is supported by the human/mouse/frog rod inner-segment study and cardiac membrane-transporter targeting. It is accurate despite the more specific plasma-membrane rows and does not imply a transmembrane segment. Propagation Review Root cause: NO FAILURE CORE Sources checked: UniProtKB-SubCell:SL-0162 UNRESOLVED Original source identifier preserved. The exact historical source assertion/construct was not independently reconstructed; target-level primary corroboration or uncertainty is stated in the row reason. |
| GO:0016323 basolateral plasma membrane | IDA PMID:15611082 The ammonium transporter RhBG: requirement of a tyrosine-bas... | UNDECIDED | Summary: Source-specific basolateral ANK2 localization remains unresolved. Reason: The accessible PMID:15611082 abstract concerns ankyrin-G-dependent RhBG targeting in MDCK cells. The full original ANK2 localization experiments have not been read. Do not equate the abstract emphasis with absence of ankyrin-B experiments or erase an experimental annotation. |
| GO:0016323 basolateral plasma membrane | IEA GO_REF:0000117 | UNDECIDED | Summary: The ARBA basolateral-membrane assignment needs its target-specific evidence traced. Reason: The exact ARBA00086715 rule and supporting ANK2 localization source were not reconstructed. The accessible RhBG/ankyrin-G abstract is insufficient to validate or refute basolateral ankyrin-B. Preserve the electronic source rather than substituting general plasma-membrane evidence for this subdomain. Propagation Review Root cause: UNRESOLVED Sources checked: ARBA:ARBA00086715 UNRESOLVED Original source identifier preserved. The exact historical source assertion/construct was not independently reconstructed; target-level primary corroboration or uncertainty is stated in the row reason. |
| GO:0016324 apical plasma membrane | IEA GO_REF:0000044 | UNDECIDED | Summary: The specialized apical-membrane pool needs its primary localization source. Reason: UniProt and mouse-orthology assertions support a candidate epithelial pool, but the specific primary ANK2 localization experiment was not inspected. General membrane anchoring does not establish apical versus basolateral localization in a polarized epithelium. Propagation Review Root cause: UNRESOLVED Sources checked: UniProtKB-SubCell:SL-0015 UNRESOLVED Original source identifier preserved. The exact historical source assertion/construct was not independently reconstructed; target-level primary corroboration or uncertainty is stated in the row reason. |
| GO:0016324 apical plasma membrane | ISS GO_REF:0000024 | UNDECIDED | Summary: The specialized apical-membrane pool needs its primary localization source. Reason: UniProt and mouse-orthology assertions support a candidate epithelial pool, but the specific primary ANK2 localization experiment was not inspected. General membrane anchoring does not establish apical versus basolateral localization in a polarized epithelium. Propagation Review Root cause: UNRESOLVED Sources checked: UniProtKB:Q8C8R3 UNRESOLVED Original source identifier preserved. The exact historical source assertion/construct was not independently reconstructed; target-level primary corroboration or uncertainty is stated in the row reason. |
| GO:0019899 enzyme binding | IPI PMID:21177872 Asparagine and aspartate hydroxylation of the cytoskeletal a... | KEEP AS NON CORE | Summary: Ankyrin-B can bind FIH as a hydroxylation substrate. Reason: Relevant full PMID:21177872 experiments use ankyrin-B repeat fragments and peptides as FIH substrates, while much erythrocyte work concerns ankyrin-R. Retain the contextual enzyme interaction with Q9NWT6 without assigning hydroxylase activity to ANK2 or treating passive substrate modification as a new core process. |
| GO:0019901 protein kinase binding | IPI PMID:18782775 Obscurin targets ankyrin-B and protein phosphatase 2A to the... | MODIFY | Summary: The obscurin interaction supports M-line adaptor activity, with an isoform-specific kinase caveat. Reason: Full PMID:18782775 tests human obscurin C-terminal and ankyrin-B regulatory constructs and supports M-line recruitment plus B56alpha/PP2A organization. Its Discussion states that the structural requirements for ankyrin binding occur only in the 800-kDa obscurin isoform, distinguishing 900-kDa and smaller kinase products. The original Q5VST9 partner is preserved. Refine this source to cytoskeletal adaptor activity; this is not a general assertion that binding a noncatalytic domain of a kinase cannot count as kinase binding. Proposed replacements: cytoskeletal adaptor activity Supporting Evidence: PMID:18782775 The structural requirements in obscurin for ankyrin binding activity are only present in the 800-kDa isoform ( 32 ). |
| GO:0030018 Z disc | IEA GO_REF:0000044 | ACCEPT | Summary: A cardiac Z-disc-associated ankyrin-B pool is supported. Reason: The inspected full localization experiments in PMID:18782775 show ankyrin-B organization in adult cardiac sarcomeres, including Z-line signal as well as the principal M-line pool. Retain the location mapping/ortholog conclusion with that tissue context. Propagation Review Root cause: NO FAILURE CORE Sources checked: UniProtKB-SubCell:SL-0314 UNRESOLVED Original source identifier preserved. The exact historical source assertion/construct was not independently reconstructed; target-level primary corroboration or uncertainty is stated in the row reason. |
| GO:0030018 Z disc | ISS GO_REF:0000024 | ACCEPT | Summary: A cardiac Z-disc-associated ankyrin-B pool is supported. Reason: The inspected full localization experiments in PMID:18782775 show ankyrin-B organization in adult cardiac sarcomeres, including Z-line signal as well as the principal M-line pool. Retain the location mapping/ortholog conclusion with that tissue context. Propagation Review Root cause: NO FAILURE CORE Sources checked: UniProtKB:Q8C8R3 UNRESOLVED Original source identifier preserved. The exact historical source assertion/construct was not independently reconstructed; target-level primary corroboration or uncertainty is stated in the row reason. |
| GO:0030315 T-tubule | IEA GO_REF:0000044 | ACCEPT | Summary: Ankyrin-B localizes to the cardiac T-tubule system. Reason: The PMID:12571597 abstract explicitly connects ankyrin-B targeting to T-tubular Na/K-ATPase, NCX and IP3 receptors. Neonatal cells lacking mature T-tubules are a different context and do not negate the adult location. Propagation Review Root cause: NO FAILURE CORE Sources checked: UniProtKB-SubCell:SL-0505 UNRESOLVED Original source identifier preserved. The exact historical source assertion/construct was not independently reconstructed; target-level primary corroboration or uncertainty is stated in the row reason. |
| GO:0030315 T-tubule | ISS GO_REF:0000024 | ACCEPT | Summary: Ankyrin-B localizes to the cardiac T-tubule system. Reason: The PMID:12571597 abstract explicitly connects ankyrin-B targeting to T-tubular Na/K-ATPase, NCX and IP3 receptors. Neonatal cells lacking mature T-tubules are a different context and do not negate the adult location. Propagation Review Root cause: NO FAILURE CORE Sources checked: UniProtKB:Q8C8R3 UNRESOLVED Original source identifier preserved. The exact historical source assertion/construct was not independently reconstructed; target-level primary corroboration or uncertainty is stated in the row reason. |
| GO:0030507 spectrin binding | IBA GO_REF:0000033 | ACCEPT | Summary: Spectrin binding is a conserved and directly supported ankyrin-B activity. Reason: The actual PAINT table has a spectrin-binding IBD at PTN002380879 with ANK1 and ANK2 descendant evidence. ANK2 self-inclusion is valid grounding, not circularity. Direct beta2-spectrin experiments and the human ANK2βmouse beta4-spectrin structural entry corroborate the activity. Propagation Review Root cause: NO FAILURE CORE Sources checked: PANTHER:PTN002380879 SUPPORTS TRANSFER Actual PTHR24123 PAINT table contains the matching IBD at PTN002380879. Full tree/MSA and all historical descendant experiments were not reconstructed. UniProtKB:P16157 UNRESOLVED Original source identifier preserved. The exact historical source assertion/construct was not independently reconstructed; target-level primary corroboration or uncertainty is stated in the row reason. UniProtKB:Q01484 SUPPORTS TRANSFER ANK2 is itself an experimentally grounded descendant source for the ancestral-node inference; this is valid PAINT provenance, not circularity. Supporting Evidence: PMID:15262991 Therefore, direct binding of beta(2)-spectrin to ankyrin-B is required for the normal targeting of beta(2)-spectrin in neonatal cardiomyocytes. |
| GO:0030507 spectrin binding | IPI PMID:15262991 Ankyrin-B targets beta2-spectrin to an intracellular compart... | ACCEPT | Summary: Ankyrin-B directly binds beta2-spectrin. Reason: PMID:15262991 directly assays ankyrin-B/spectrin interaction and separates it with binding-defective mutants from spectrin-independent ankyrin-B functions. Retain this specific functional binding activity. Supporting Evidence: PMID:15262991 Therefore, direct binding of beta(2)-spectrin to ankyrin-B is required for the normal targeting of beta(2)-spectrin in neonatal cardiomyocytes. |
| GO:0030674 protein-macromolecule adaptor activity | ISS GO_REF:0000024 | ACCEPT | Summary: Ankyrin-B mediates several nonenzymatic macromolecular adaptor interactions. Reason: Cytoskeletal anchoring is a major subclass of the conserved adaptor activity, but does not exhaust the source-supported function. PMID:27718357 shows human AnkB death-domain interaction with mouse RabGAP1L and AnkB-dependent recruitment of RabGAP1L to PI3P-positive organelles in mouse fibroblasts. PMID:34812142 additionally resolves giant AnkB-dependent surface receptor organization that can support Sema3A responses without betaII-spectrin or microtubule binding. Retain the broad original adaptor assertion rather than narrowing all mechanisms to the cytoskeletal subclass. RabGAP1L supplies the GAP chemistry; neither study establishes intrinsic ANK2 enzymatic activity. This is mammalian target-level corroboration; the exact historical mouse transfer record has not been reconstructed. Propagation Review Root cause: NO FAILURE CORE Sources checked: UniProtKB:Q8C8R3 UNRESOLVED Original source identifier preserved. The exact historical source assertion/construct was not independently reconstructed; target-level primary corroboration or uncertainty is stated in the row reason. Supporting Evidence: PMID:27718357 Together, these results reveal a new protein-protein interaction between AnkB and RabGAP1L that recruits RabGAP1L to PI3P-positive organelles. |
| GO:0030913 paranodal junction assembly | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Ankyrin-B contributes to paranodal assembly in a glial and compensatory context. Reason: PMID:25362471 distinguishes 220-kDa glial ankyrin-B from neuronal giant ankyrin-B and oligodendrocyte ankyrin-G. Although AnkB loss alone leaves PNS paranodes intact, deleting both AnkB and AnkG in mouse oligodendrocytes worsens the AnkG assembly phenotype; NF155 coassociation supports a structural contribution beyond necessity alone. Retain this specialized assembly context as non-core, without making AnkB universally required or attributing AnkG-only experiments to it. The exact historical rat Ensembl transfer record remains unreconstructed. Propagation Review Root cause: NO FAILURE NON CORE Sources checked: UniProtKB:F1M5N3 UNRESOLVED Original source identifier preserved. The exact historical source assertion/construct was not independently reconstructed; target-level primary corroboration or uncertainty is stated in the row reason. ensembl:ENSRNOP00000035307 UNRESOLVED Original source identifier preserved. The exact historical source assertion/construct was not independently reconstructed; target-level primary corroboration or uncertainty is stated in the row reason. Supporting Evidence: PMID:25362471 Thus, AnkB can partially compensate for the loss of AnkG in oligodendrocytes. |
| GO:0031430 M band | IEA GO_REF:0000044 | ACCEPT | Summary: Ankyrin-B localizes at the cardiac M-band. Reason: Full PMID:18782775 provides localization and obscurin-dependent targeting evidence; PMID:15262991 independently places ankyrin-B/beta2-spectrin over the M-line in neonatal cardiomyocytes. Retain the specific sarcomeric location. Propagation Review Root cause: NO FAILURE CORE Sources checked: UniProtKB-SubCell:SL-0315 UNRESOLVED Original source identifier preserved. The exact historical source assertion/construct was not independently reconstructed; target-level primary corroboration or uncertainty is stated in the row reason. |
| GO:0031430 M band | ISS GO_REF:0000024 | ACCEPT | Summary: Ankyrin-B localizes at the cardiac M-band. Reason: Full PMID:18782775 provides localization and obscurin-dependent targeting evidence; PMID:15262991 independently places ankyrin-B/beta2-spectrin over the M-line in neonatal cardiomyocytes. Retain the specific sarcomeric location. Propagation Review Root cause: NO FAILURE CORE Sources checked: UniProtKB:Q8C8R3 UNRESOLVED Original source identifier preserved. The exact historical source assertion/construct was not independently reconstructed; target-level primary corroboration or uncertainty is stated in the row reason. |
| GO:0031647 regulation of protein stability | IC PMID:18832177 Dysfunction in ankyrin-B-dependent ion channel and transport... | ACCEPT | Summary: Regulation of target-protein stability is independently demonstrated. Reason: The IC premise GO:0010628 does not by itself distinguish biosynthesis from posttranslational stabilization, and that source-specific gene-expression row remains unresolved. Independently, PMID:17178715 explicitly demonstrates ankyrin-B-dependent NCX1 posttranslational stability. Accept the true target function without certifying the historical IC premise or alleging circularity. Propagation Review Root cause: NO FAILURE CORE Sources checked: GO:0010628 UNRESOLVED Original source identifier preserved. The exact historical source assertion/construct was not independently reconstructed; target-level primary corroboration or uncertainty is stated in the row reason. Supporting Evidence: PMID:17178715 we demonstrate that direct interaction with the membrane adaptor ankyrin-B is required for the localization and post-translational stability of Na/Ca exchanger 1 in neonatal mouse cardiomyocytes. |
| GO:0031672 A band | ISS GO_REF:0000024 | UNDECIDED | Summary: A-band assignment needs its distinct ankyrin-B localization evidence. Reason: The inspected primary paper directly supports M-line and Z-line organization and discusses obscurin-related A-band formation. That does not by itself establish ankyrin-B throughout the A-band. The original mouse localization experiment for this transferred row remains uninspected; no absence is inferred from this limitation. Propagation Review Root cause: UNRESOLVED Sources checked: UniProtKB:Q8C8R3 UNRESOLVED Original source identifier preserved. The exact historical source assertion/construct was not independently reconstructed; target-level primary corroboration or uncertainty is stated in the row reason. |
| GO:0033292 T-tubule organization | ISS GO_REF:0000024 | UNDECIDED | Summary: T-tubule morphology and membrane-target positioning are distinct claims. Reason: Ankyrin-B clearly positions ion-handling proteins in the T-tubule system, but the original mouse evidence for T-tubule organization as a structural process was not traced. Preserve uncertainty rather than equating cargo mislocalization with altered tubule morphogenesis. Propagation Review Root cause: UNRESOLVED Sources checked: UniProtKB:Q8C8R3 UNRESOLVED Original source identifier preserved. The exact historical source assertion/construct was not independently reconstructed; target-level primary corroboration or uncertainty is stated in the row reason. |
| GO:0034394 protein localization to cell surface | ISS GO_REF:0000024 | ACCEPT | Summary: Ankyrin-B supports delivery/retention of protein targets at the cell surface. Reason: Direct NCX1 and dystrophin targeting evidence supports the general cell-surface positioning role independently of the uninspected historical mouse transfer. This is a structural adaptor contribution to trafficking, not a vesicle-fusion catalyst. Propagation Review Root cause: NO FAILURE CORE Sources checked: UniProtKB:Q8C8R3 UNRESOLVED Original source identifier preserved. The exact historical source assertion/construct was not independently reconstructed; target-level primary corroboration or uncertainty is stated in the row reason. Supporting Evidence: PMID:17178715 we demonstrate that direct interaction with the membrane adaptor ankyrin-B is required for the localization and post-translational stability of Na/Ca exchanger 1 in neonatal mouse cardiomyocytes. |
| GO:0036309 protein localization to M-band | ISS GO_REF:0000024 | ACCEPT | Summary: Ankyrin-B helps position associated proteins at the M-band. Reason: Full PMID:18782775 connects obscurin-dependent ankyrin-B recruitment with M-line B56alpha/PP2A localization. Ankyrin-B supplies part of the local anchoring structure; the process is supported beyond loss-of-function necessity alone. Propagation Review Root cause: NO FAILURE CORE Sources checked: UniProtKB:Q8C8R3 UNRESOLVED Original source identifier preserved. The exact historical source assertion/construct was not independently reconstructed; target-level primary corroboration or uncertainty is stated in the row reason. |
| GO:0036371 protein localization to T-tubule | ISS GO_REF:0000024 | ACCEPT | Summary: Ankyrin-B organizes calcium-handling proteins in the T-tubule system. Reason: PMID:12571597 explicitly describes defective T-tubular targeting of Na/K-ATPase, NCX and IP3 receptors when ankyrin-B function is reduced. Retain the positioning process with its cardiac context. Propagation Review Root cause: NO FAILURE CORE Sources checked: UniProtKB:Q8C8R3 UNRESOLVED Original source identifier preserved. The exact historical source assertion/construct was not independently reconstructed; target-level primary corroboration or uncertainty is stated in the row reason. |
| GO:0042383 sarcolemma | ISS GO_REF:0000024 | ACCEPT | Summary: Ankyrin-B is associated with the muscle sarcolemma. Reason: The muscle dystrophin-targeting study supports sarcolemmal organization by ankyrin-B, complemented by cardiac membrane-channel evidence. Preserve the distinction between ankyrin-B delivery and ankyrin-G retention mechanisms. Propagation Review Root cause: NO FAILURE CORE Sources checked: UniProtKB:Q8C8R3 UNRESOLVED Original source identifier preserved. The exact historical source assertion/construct was not independently reconstructed; target-level primary corroboration or uncertainty is stated in the row reason. Supporting Evidence: PMID:19109891 Ankyrin-B thus is an adaptor required for sarcolemmal localization of dystrophin, as well as dynactin-4. |
| GO:0043005 neuron projection | IBA GO_REF:0000033 | ACCEPT | Summary: Ankyrin-B has a conserved neuronal-projection-associated pool. Reason: The actual PAINT IBD at PTN002380879 includes neuron projection. Its donor list is not assessed as a pairwise-transfer score. Independent giant-ankyrin-B neuronal studies identified during primary research and the human induced-neuron source corroborate neuronal biology; precise axonal versus dendritic and isoform contexts are kept separate. The recovered giant-isoform studies directly examine axons, collateral branches and growth cones; their targeted Methods/Results preserve mouse-host and human-construct distinctions. Propagation Review Root cause: NO FAILURE CORE Sources checked: PANTHER:PTN002380879 SUPPORTS TRANSFER Actual PTHR24123 PAINT table contains the matching IBD at PTN002380879. Full tree/MSA and all historical descendant experiments were not reconstructed. RGD:1309620 UNRESOLVED Original source identifier preserved. The exact historical source assertion/construct was not independently reconstructed; target-level primary corroboration or uncertainty is stated in the row reason. UniProtKB:Q12955 UNRESOLVED Original source identifier preserved. The exact historical source assertion/construct was not independently reconstructed; target-level primary corroboration or uncertainty is stated in the row reason. Supporting Evidence: PMID:34812142 These results indicate a selective requirement for AnkB440 for cortical neuron responses to the GC collapse-inducing effect of Sema 3 A. |
| GO:0043034 costamere | ISS GO_REF:0000024 | UNDECIDED | Summary: The costamere location requires distinguishing transport from stable retention. Reason: The PMID:19109891 abstract separates ankyrin-B-dependent dystrophin delivery from ankyrin-G-dependent retention at costameres. The full localization experiment underlying the mouse transfer was not inspected. This distinction motivates checking the source, not asserting ankyrin-B is absent from costameres. Propagation Review Root cause: UNRESOLVED Sources checked: UniProtKB:Q8C8R3 UNRESOLVED Original source identifier preserved. The exact historical source assertion/construct was not independently reconstructed; target-level primary corroboration or uncertainty is stated in the row reason. |
| GO:0044325 transmembrane transporter binding | IBA GO_REF:0000033 | ACCEPT | Summary: Binding membrane transporters is a conserved ankyrin-B function. Reason: The actual PAINT IBD at PTN002380879 is grounded in ANK2 descendant experiments. The target appearing in its own WITH/FROM is correct. Independent NCX1, Kir6.2 and Cav1.3 interactions support the specific molecular activity without inferring ion-transporter catalysis. Propagation Review Root cause: NO FAILURE CORE Sources checked: PANTHER:PTN002380879 SUPPORTS TRANSFER Actual PTHR24123 PAINT table contains the matching IBD at PTN002380879. Full tree/MSA and all historical descendant experiments were not reconstructed. UniProtKB:Q01484 SUPPORTS TRANSFER ANK2 is itself an experimentally grounded descendant source for the ancestral-node inference; this is valid PAINT provenance, not circularity. Supporting Evidence: PMID:17178715 we demonstrate that direct interaction with the membrane adaptor ankyrin-B is required for the localization and post-translational stability of Na/Ca exchanger 1 in neonatal mouse cardiomyocytes. |
| GO:0044325 transmembrane transporter binding | IPI PMID:20610380 Ankyrin-B regulates Kir6.2 membrane expression and function ... | ACCEPT | Summary: Ankyrin-B binds the Kir6.2 channel subunit. Reason: PMID:20610380 explicitly reports association of cardiac ankyrin-B with Kir6.2 and effects on its membrane expression/function. The source Q14654 partner is retained. Accept the specific transporter-binding activity independently of unresolved direction-specific gating or potassium-flux claims. |
| GO:0044325 transmembrane transporter binding | IPI PMID:21859974 Defects in ankyrin-based membrane protein targeting pathways... | ACCEPT | Summary: Ankyrin-B binds the Cav1.3 channel C-terminal region. Reason: Full PMID:21859974 includes binding-domain mapping and functional targeting experiments. The source P27732 partner is rat Cacna1d, and its organism is not rewritten as human. This supports membrane-transporter binding rather than direct calcium conduction by ankyrin-B. |
| GO:0044325 transmembrane transporter binding | ISS GO_REF:0000024 | ACCEPT | Summary: The orthologous transporter-binding assignment agrees with target experiments. Reason: NCX1, Kir6.2 and Cav1.3 experiments independently establish ANK2 binding to membrane transporters. The mouse source is a conserved-activity transfer, with precise construct species retained in the source-specific rows. Propagation Review Root cause: NO FAILURE CORE Sources checked: UniProtKB:Q8C8R3 UNRESOLVED Original source identifier preserved. The exact historical source assertion/construct was not independently reconstructed; target-level primary corroboration or uncertainty is stated in the row reason. Supporting Evidence: PMID:17178715 we demonstrate that direct interaction with the membrane adaptor ankyrin-B is required for the localization and post-translational stability of Na/Ca exchanger 1 in neonatal mouse cardiomyocytes. |
| GO:0045211 postsynaptic membrane | IEA GO_REF:0000044 | UNDECIDED | Summary: Postsynaptic membrane localization needs its specific original experiment. Reason: A neuronal or synaptic-protein interaction does not by itself establish the postsynaptic membrane compartment. The UniProt mapping and mouse-orthology records are preserved while the precise ANK2 isoform/cell localization experiment remains uninspected. No ankyrin-G localization is silently substituted. Propagation Review Root cause: UNRESOLVED Sources checked: UniProtKB-SubCell:SL-0219 UNRESOLVED Original source identifier preserved. The exact historical source assertion/construct was not independently reconstructed; target-level primary corroboration or uncertainty is stated in the row reason. |
| GO:0045211 postsynaptic membrane | ISS GO_REF:0000024 | UNDECIDED | Summary: Postsynaptic membrane localization needs its specific original experiment. Reason: A neuronal or synaptic-protein interaction does not by itself establish the postsynaptic membrane compartment. The UniProt mapping and mouse-orthology records are preserved while the precise ANK2 isoform/cell localization experiment remains uninspected. No ankyrin-G localization is silently substituted. Propagation Review Root cause: UNRESOLVED Sources checked: UniProtKB:Q8C8R3 UNRESOLVED Original source identifier preserved. The exact historical source assertion/construct was not independently reconstructed; target-level primary corroboration or uncertainty is stated in the row reason. |
| GO:0050821 protein stabilization | ISS PMID:17178715 Targeting and stability of Na/Ca exchanger 1 in cardiomyocyt... | ACCEPT | Summary: Ankyrin-B stabilizes its NCX1 membrane target. Reason: PMID:17178715 explicitly identifies posttranslational NCX1 stability as dependent on direct ankyrin-B binding. This supports protein stabilization without equating it with increased transcription or translation. Propagation Review Root cause: NO FAILURE CORE Sources checked: UniProtKB:Q8C8R3 UNRESOLVED Original source identifier preserved. The exact historical source assertion/construct was not independently reconstructed; target-level primary corroboration or uncertainty is stated in the row reason. Supporting Evidence: PMID:17178715 we demonstrate that direct interaction with the membrane adaptor ankyrin-B is required for the localization and post-translational stability of Na/Ca exchanger 1 in neonatal mouse cardiomyocytes. |
| GO:0051117 ATPase binding | ISS GO_REF:0000024 | ACCEPT | Summary: Na/K-ATPase is part of an ankyrin-B-associated membrane complex. Reason: The cardiac Kir6.2 study reports an ankyrin-B membrane complex with Na/K-ATPase, consistent with the established pump-targeting mechanism. Retain the mouse-derived ATPase-binding assignment; this does not make ANK2 an ATPase and does not claim that this abstract proves a purified binary interaction. Propagation Review Root cause: NO FAILURE CORE Sources checked: UniProtKB:Q8C8R3 UNRESOLVED Original source identifier preserved. The exact historical source assertion/construct was not independently reconstructed; target-level primary corroboration or uncertainty is stated in the row reason. |
| GO:0051279 regulation of release of sequestered calcium ion into cytosol | IGI PMID:17242276 Defining the cellular phenotype of "ankyrin-B syndrome" vari... | ACCEPT | Summary: Ankyrin-B-dependent target organization influences calcium release into the cytosol. Reason: The source abstract reports variant-dependent cardiomyocyte effects, while full independent PMID:15178757 demonstrates rescue of calcium dynamics and IP3R positioning by human ankyrin-B. The accessible PMID:19098452 abstract specifically reports slow and irregular Ca2+ release in ankyrin-B-deficient sinoatrial cardiomyocytes, corroborating the release-regulation role. Accept regulation through the adaptor mechanism without assigning direct channel-opening chemistry or a universal effect on every calcium-release channel. Propagation Review Root cause: NO FAILURE CORE Sources checked: UniProtKB:Q8C8R3 UNRESOLVED Original source identifier preserved. The exact historical source assertion/construct was not independently reconstructed; target-level primary corroboration or uncertainty is stated in the row reason. Supporting Evidence: PMID:19098452 Loss of ankyrin-B promoted slow and irregular Ca2+ release, as well as afterdepolarizations in isolated SAN cardiomyocytes. |
| GO:0051597 response to methylmercury | IEA GO_REF:0000107 | UNDECIDED | Summary: The methylmercury response transfer needs evidence of an active ANK2 contribution. Reason: The normal PMID:12949909 record is abstract-only. It reports selective disappearance of the 440-kDa ankyrin-B protein after methylmercury exposure of primary rat cerebellar cultures and interprets the loss as associated with early axonal degeneration. Depletion as an injury marker does not by itself establish that ankyrin-B performs the response. The actual historical donor assertion and full experimental article remain unavailable, so preserve source-specific UNDECIDED rather than declaring the electronic transfer false. Propagation Review Root cause: UNRESOLVED Sources checked: UniProtKB:F1M5N3 UNRESOLVED Original source identifier preserved. The exact historical source assertion/construct was not independently reconstructed; target-level primary corroboration or uncertainty is stated in the row reason. ensembl:ENSRNOP00000035307 UNRESOLVED Original source identifier preserved. The exact historical source assertion/construct was not independently reconstructed; target-level primary corroboration or uncertainty is stated in the row reason. Supporting Evidence: PMID:12949909 These results indicate that selective loss of the axonal protein 440-kDa ankyrinB is associated with the early stage of degeneration of cerebellar neurons induced by methylmercury. |
| GO:0051924 regulation of calcium ion transport | IGI PMID:12571597 Ankyrin-B mutation causes type 4 long-QT cardiac arrhythmia ... | ACCEPT | Summary: Ankyrin-B regulates calcium transport by organizing channels and exchangers. Reason: The original disease/variant studies connect reduced ankyrin-B function with abnormal NCX, pump and IP3R organization and calcium handling; full PMID:15178757 includes rescue with human ankyrin-B. The protein supplies a functional structural link rather than conducting calcium itself. Propagation Review Root cause: NO FAILURE CORE Sources checked: UniProtKB:Q8C8R3 UNRESOLVED Original source identifier preserved. The exact historical source assertion/construct was not independently reconstructed; target-level primary corroboration or uncertainty is stated in the row reason. |
| GO:0051924 regulation of calcium ion transport | IGI PMID:15178757 A cardiac arrhythmia syndrome caused by loss of ankyrin-B fu... | ACCEPT | Summary: Ankyrin-B regulates calcium transport by organizing channels and exchangers. Reason: The original disease/variant studies connect reduced ankyrin-B function with abnormal NCX, pump and IP3R organization and calcium handling; full PMID:15178757 includes rescue with human ankyrin-B. The protein supplies a functional structural link rather than conducting calcium itself. Propagation Review Root cause: NO FAILURE CORE Sources checked: UniProtKB:Q8C8R3 UNRESOLVED Original source identifier preserved. The exact historical source assertion/construct was not independently reconstructed; target-level primary corroboration or uncertainty is stated in the row reason. |
| GO:0051928 positive regulation of calcium ion transport | ISS GO_REF:0000024 | UNDECIDED | Summary: The positive direction of the calcium-transport effect depends on the target and assay. Reason: Ankyrin-B regulates several transporters with different transport directions and modes. The specific mouse experiment supporting positive regulation, rather than general regulation, has not been traced. Do not assign a uniform positive calcium flux from membrane localization alone. Propagation Review Root cause: UNRESOLVED Sources checked: UniProtKB:Q8C8R3 UNRESOLVED Original source identifier preserved. The exact historical source assertion/construct was not independently reconstructed; target-level primary corroboration or uncertainty is stated in the row reason. |
| GO:0055037 recycling endosome | IEA GO_REF:0000044 | ACCEPT | Summary: A recycling-endosomal ankyrin-B pool is directly observed. Reason: PMID:27718357 reports partial overlap of 220-kDa AnkB-mCherry with Rab11-positive recycling endosomes in mouse embryonic fibroblasts. The preferred early-endosome localization and partial Rab11 overlap are distinct observations, so retain the original recycling-endosome assertion with its restricted experimental context. This is not inferred solely from a recycling phenotype or generalized to all splice isoforms. Propagation Review Root cause: NO FAILURE CORE Sources checked: UniProtKB-SubCell:SL-0232 UNRESOLVED Original source identifier preserved. The exact historical source assertion/construct was not independently reconstructed; target-level primary corroboration or uncertainty is stated in the row reason. Supporting Evidence: PMID:27718357 Although WT AnkB-mCherry expressed was preferentially localized to Rab5-positive early endosomes, it also exhibited partial overlap with Rab11-positive recycling endosomes and LAMP1-positive lysosomes. |
| GO:0055037 recycling endosome | ISS GO_REF:0000024 | ACCEPT | Summary: A recycling-endosomal ankyrin-B pool is directly observed. Reason: PMID:27718357 reports partial overlap of 220-kDa AnkB-mCherry with Rab11-positive recycling endosomes in mouse embryonic fibroblasts. The preferred early-endosome localization and partial Rab11 overlap are distinct observations, so retain the original recycling-endosome assertion with its restricted experimental context. This is not inferred solely from a recycling phenotype or generalized to all splice isoforms. Propagation Review Root cause: NO FAILURE CORE Sources checked: UniProtKB:Q8C8R3 UNRESOLVED Original source identifier preserved. The exact historical source assertion/construct was not independently reconstructed; target-level primary corroboration or uncertainty is stated in the row reason. Supporting Evidence: PMID:27718357 Although WT AnkB-mCherry expressed was preferentially localized to Rab5-positive early endosomes, it also exhibited partial overlap with Rab11-positive recycling endosomes and LAMP1-positive lysosomes. |
| GO:0055117 regulation of cardiac muscle contraction | IMP PMID:15178757 A cardiac arrhythmia syndrome caused by loss of ankyrin-B fu... | ACCEPT | Summary: Ankyrin-B regulates cardiac muscle contraction through target organization. Reason: Full PMID:15178757 reports contraction and calcium-handling defects in deficient cardiomyocytes and rescue by human ankyrin-B, with disease variants showing reduced rescue. The membrane adaptor mechanism supplies the causal cellular contribution. |
| GO:0060307 regulation of ventricular cardiac muscle cell membrane repolarization | IMP PMID:18832177 Dysfunction in ankyrin-B-dependent ion channel and transport... | UNDECIDED | Summary: The precise ventricular-repolarization assertion is not resolved by the sinus-node abstract. Reason: PMID:18832177 exposes sinus-node disease and pacing/channel-organization findings in its abstract, not the full ventricular experiment. Adult ventricular and neonatal-null findings differ across the broader literature. Preserve this experimental source assertion pending direct inspection rather than substituting a generic long-QT disease label. |
| GO:0060342 photoreceptor inner segment membrane | ISS GO_REF:0000024 | ACCEPT | Summary: Ankyrin-B localizes to rod inner-segment membrane machinery. Reason: PMID:19007774 explicitly examines humans, mice and frogs and places ankyrin-B in inner segments with Na/K-ATPase and NCX. It independently corroborates the mouse-orthology compartment assignment. Propagation Review Root cause: NO FAILURE CORE Sources checked: UniProtKB:Q8C8R3 UNRESOLVED Original source identifier preserved. The exact historical source assertion/construct was not independently reconstructed; target-level primary corroboration or uncertainty is stated in the row reason. |
| GO:0070296 sarcoplasmic reticulum calcium ion transport | TAS PMID:19098452 Ankyrin-based targeting pathway regulates human sinoatrial n... | MODIFY | Summary: The supported ankyrin role is regulation of calcium transport. Reason: The accessible PMID:19098452 summary establishes targeting and organization of NCX1, Na+/K+ ATPase, IP3R and CaV1.3, with consequent changes in calcium release and automaticity. This source supports regulation of calcium transport through the adaptor mechanism; it does not establish ankyrin-B as a structural participant in the sarcoplasmic-reticulum transport step itself. Structural scaffolds can participate in transport processes when the experiment demonstrates that role, so lack of transporter catalysis is not the exclusion criterion. Refine this literature assertion to the existing regulation-of-calcium-transport process and consolidate duplicate coverage. Proposed replacements: regulation of calcium ion transport |
| GO:0070972 protein localization to endoplasmic reticulum | IGI PMID:15178757 A cardiac arrhythmia syndrome caused by loss of ankyrin-B fu... | ACCEPT | Summary: Ankyrin-B helps position IP3 receptors in the intracellular membrane system. Reason: Full PMID:15178757 examines abnormal IP3-receptor distribution and its rescue by human ankyrin-B constructs in deficient neonatal cardiomyocytes. This supports protein positioning in the ER-related membrane system; the annotation does not require ankyrin-B to be an ER lumen protein. Propagation Review Root cause: NO FAILURE CORE Sources checked: UniProtKB:Q8C8R3 UNRESOLVED Original source identifier preserved. The exact historical source assertion/construct was not independently reconstructed; target-level primary corroboration or uncertainty is stated in the row reason. |
| GO:0072659 protein localization to plasma membrane | IBA GO_REF:0000033 | ACCEPT | Summary: Plasma-membrane protein positioning is a conserved ankyrin function. Reason: The actual PAINT IBD at PTN002380879 includes plasma-membrane protein localization, with human ANK2 among descendant experimental sources. Self-inclusion and a limited donor list are not failures. Direct NCX1, channel and dystrophin targeting establish the same process on ANK2. Propagation Review Root cause: NO FAILURE CORE Sources checked: PANTHER:PTN002380879 SUPPORTS TRANSFER Actual PTHR24123 PAINT table contains the matching IBD at PTN002380879. Full tree/MSA and all historical descendant experiments were not reconstructed. UniProtKB:P16157 UNRESOLVED Original source identifier preserved. The exact historical source assertion/construct was not independently reconstructed; target-level primary corroboration or uncertainty is stated in the row reason. UniProtKB:Q01484 SUPPORTS TRANSFER ANK2 is itself an experimentally grounded descendant source for the ancestral-node inference; this is valid PAINT provenance, not circularity. UniProtKB:Q12955 UNRESOLVED Original source identifier preserved. The exact historical source assertion/construct was not independently reconstructed; target-level primary corroboration or uncertainty is stated in the row reason. Supporting Evidence: PMID:17178715 we demonstrate that direct interaction with the membrane adaptor ankyrin-B is required for the localization and post-translational stability of Na/Ca exchanger 1 in neonatal mouse cardiomyocytes. |
| GO:0072659 protein localization to plasma membrane | IEA GO_REF:0000117 | ACCEPT | Summary: The electronic positioning assignment agrees with direct target evidence. Reason: Although the historical ARBA00029169 rule was not reconstructed, independent ANK2 membrane-targeting experiments support the same biological conclusion. Accept the function without asserting that every member of the machine rule has the same mechanism. Propagation Review Root cause: NO FAILURE CORE Sources checked: ARBA:ARBA00029169 UNRESOLVED Original source identifier preserved. The exact historical source assertion/construct was not independently reconstructed; target-level primary corroboration or uncertainty is stated in the row reason. Supporting Evidence: PMID:17178715 we demonstrate that direct interaction with the membrane adaptor ankyrin-B is required for the localization and post-translational stability of Na/Ca exchanger 1 in neonatal mouse cardiomyocytes. |
| GO:0072659 protein localization to plasma membrane | IGI PMID:17178715 Targeting and stability of Na/Ca exchanger 1 in cardiomyocyt... | ACCEPT | Summary: Direct ankyrin-B association targets NCX1 to the plasma membrane. Reason: PMID:17178715 identifies binding-defective NCX1 variants and reduced ankyrin-B as causes of mislocalization and loss of posttranslational stability. This directly supports the scaffold-dependent protein-positioning process. Propagation Review Root cause: NO FAILURE CORE Sources checked: UniProtKB:Q8C8R3 UNRESOLVED Original source identifier preserved. The exact historical source assertion/construct was not independently reconstructed; target-level primary corroboration or uncertainty is stated in the row reason. Supporting Evidence: PMID:17178715 we demonstrate that direct interaction with the membrane adaptor ankyrin-B is required for the localization and post-translational stability of Na/Ca exchanger 1 in neonatal mouse cardiomyocytes. |
| GO:0072659 protein localization to plasma membrane | IMP PMID:19805355 Dual role of K ATP channel C-terminal motif in membrane targ... | ACCEPT | Summary: Ankyrin-B binding is important for Kir6.2 membrane targeting. Reason: The PMID:19805355 abstract identifies a Kir6.2 C-terminal binding motif with a trafficking role. This supports plasma-membrane protein localization without resolving the separate gating-direction or potassium-import assertions. |
| GO:0072659 protein localization to plasma membrane | ISS GO_REF:0000024 | ACCEPT | Summary: The mouse transfer agrees with directly demonstrated membrane-target positioning. Reason: NCX1 and Cav1.3 studies independently support ANK2-dependent plasma-membrane targeting, including human-protein/mouse-cell experiments. Retain the conserved function while keeping the exact ortholog donor provenance intact. Propagation Review Root cause: NO FAILURE CORE Sources checked: UniProtKB:Q8C8R3 UNRESOLVED Original source identifier preserved. The exact historical source assertion/construct was not independently reconstructed; target-level primary corroboration or uncertainty is stated in the row reason. Supporting Evidence: PMID:17178715 we demonstrate that direct interaction with the membrane adaptor ankyrin-B is required for the localization and post-translational stability of Na/Ca exchanger 1 in neonatal mouse cardiomyocytes. |
| GO:0072659 protein localization to plasma membrane | ISS PMID:21859974 Defects in ankyrin-based membrane protein targeting pathways... | ACCEPT | Summary: Ankyrin-B positions Cav1.3 at the atrial cell membrane. Reason: Full PMID:21859974 maps binding-dependent membrane localization of Cav1.3 and links reduced ankyrin-B to decreased membrane channel/current. This is direct participation through the anchoring mechanism, not a new ion-channel catalytic activity. Propagation Review Root cause: NO FAILURE CORE Sources checked: UniProtKB:Q8C8R3 UNRESOLVED Original source identifier preserved. The exact historical source assertion/construct was not independently reconstructed; target-level primary corroboration or uncertainty is stated in the row reason. |
| GO:0086004 regulation of cardiac muscle cell contraction | IGI PMID:17242276 Defining the cellular phenotype of "ankyrin-B syndrome" vari... | ACCEPT | Summary: Cardiomyocyte contraction depends on ankyrin-B-organized calcium machinery. Reason: The source variant study supports cellular consequences, and full independent PMID:15178757 documents contraction/calcium rescue by human ankyrin-B in deficient cardiomyocytes. Retain cellular contraction regulation without claiming all variants have identical effects. Propagation Review Root cause: NO FAILURE CORE Sources checked: UniProtKB:Q8C8R3 UNRESOLVED Original source identifier preserved. The exact historical source assertion/construct was not independently reconstructed; target-level primary corroboration or uncertainty is stated in the row reason. |
| GO:0086005 ventricular cardiac muscle cell action potential | IMP PMID:17242276 Defining the cellular phenotype of "ankyrin-B syndrome" vari... | UNDECIDED | Summary: The source-specific ventricular action-potential experiment remains uninspected. Reason: PMID:17242276 is abstract-only and does not expose the exact ventricular recording, cell stage or variant. Independent adult ventricular negative results in one model cannot exclude a result in another. Defer judgment until the supporting full experiment can be checked. |
| GO:0086014 atrial cardiac muscle cell action potential | IMP PMID:17242276 Defining the cellular phenotype of "ankyrin-B syndrome" vari... | ACCEPT | Summary: Ankyrin-B contributes to atrial electrical function through channel positioning. Reason: The original abstract-only source remains incompletely inspected, but full independent PMID:21859974 directly measures shortened atrial action potentials and altered calcium currents in deficient cardiomyocytes and maps the Cav1.3 targeting mechanism. This independently establishes the process without claiming the older source-specific recordings were reread. |
| GO:0086014 atrial cardiac muscle cell action potential | IMP PMID:18832177 Dysfunction in ankyrin-B-dependent ion channel and transport... | ACCEPT | Summary: Ankyrin-B contributes to atrial electrical function through channel positioning. Reason: The original abstract-only source remains incompletely inspected, but full independent PMID:21859974 directly measures shortened atrial action potentials and altered calcium currents in deficient cardiomyocytes and maps the Cav1.3 targeting mechanism. This independently establishes the process without claiming the older source-specific recordings were reread. |
| GO:0086014 atrial cardiac muscle cell action potential | IMP PMID:21859974 Defects in ankyrin-based membrane protein targeting pathways... | ACCEPT | Summary: The atrial action-potential contribution is directly measured. Reason: Full PMID:21859974 reports shortened atrial action potentials and reduced calcium currents in ankyrin-B-deficient cardiomyocytes, with Cav1.3 localization/binding experiments. Retain the electrical-process role through channel organization. |
| GO:0086015 SA node cell action potential | ISS GO_REF:0000024 | ACCEPT | Summary: Ankyrin-B-organized transporters contribute to sinoatrial-node electrical activity. Reason: PMID:18832177 and the mechanistic summary PMID:19098452 directly connect deficient ankyrin-B targeting to slow/irregular sinoatrial-node activity. The mouse-orthology assertion is biologically corroborated; ANK2 is a scaffold rather than a pacemaker current channel. Propagation Review Root cause: NO FAILURE CORE Sources checked: UniProtKB:Q8C8R3 UNRESOLVED Original source identifier preserved. The exact historical source assertion/construct was not independently reconstructed; target-level primary corroboration or uncertainty is stated in the row reason. |
| GO:0086046 membrane depolarization during SA node cell action potential | TAS PMID:19098452 Ankyrin-based targeting pathway regulates human sinoatrial n... | KEEP AS NON CORE | Summary: Ankyrin-B supports the membrane machinery underlying pacemaker depolarization. Reason: PMID:19098452 describes defective sinoatrial channel/transporter targeting, slow/irregular calcium release and afterdepolarizations. Retain this integrated pacemaker output as contextual physiology of the adaptor mechanism, without attributing direct depolarizing ion flux to ankyrin-B. |
| GO:0086066 atrial cardiac muscle cell to AV node cell communication | ISS GO_REF:0000024 | UNDECIDED | Summary: Atrial-to-AV-node communication needs its specific source experiment. Reason: General cardiac conduction and channel-positioning defects do not identify the particular cell-to-cell communication step asserted here. The mouse donor experiment for atrial cardiomyocyte to AV-node communication was not recovered, so the narrow transferred process remains unresolved. Propagation Review Root cause: UNRESOLVED Sources checked: UniProtKB:Q8C8R3 UNRESOLVED Original source identifier preserved. The exact historical source assertion/construct was not independently reconstructed; target-level primary corroboration or uncertainty is stated in the row reason. |
| GO:0086070 SA node cell to atrial cardiac muscle cell communication | IMP PMID:12571597 Ankyrin-B mutation causes type 4 long-QT cardiac arrhythmia ... | UNDECIDED | Summary: The precise sinoatrial-to-atrial communication step is not isolated by the inspected evidence. Reason: The cited study supports cardiac electrical phenotypes, but the relevant full experiment for this specific communication process was not inspected or isolated. Altered intrinsic pacemaking or atrial action potentials does not automatically demonstrate the particular cell-to-cell coupling step. Preserve the experimental assertion for source-specific follow-up rather than remove it from disease-level inference. |
| GO:0086070 SA node cell to atrial cardiac muscle cell communication | IMP PMID:18832177 Dysfunction in ankyrin-B-dependent ion channel and transport... | UNDECIDED | Summary: The precise sinoatrial-to-atrial communication step is not isolated by the inspected evidence. Reason: The cited study supports cardiac electrical phenotypes, but the relevant full experiment for this specific communication process was not inspected or isolated. Altered intrinsic pacemaking or atrial action potentials does not automatically demonstrate the particular cell-to-cell coupling step. Preserve the experimental assertion for source-specific follow-up rather than remove it from disease-level inference. |
| GO:0086070 SA node cell to atrial cardiac muscle cell communication | IMP PMID:21859974 Defects in ankyrin-based membrane protein targeting pathways... | UNDECIDED | Summary: The precise sinoatrial-to-atrial communication step is not isolated by the inspected evidence. Reason: The cited study supports cardiac electrical phenotypes, but the relevant full experiment for this specific communication process was not inspected or isolated. Altered intrinsic pacemaking or atrial action potentials does not automatically demonstrate the particular cell-to-cell coupling step. Preserve the experimental assertion for source-specific follow-up rather than remove it from disease-level inference. |
| GO:0086091 regulation of heart rate by cardiac conduction | IMP PMID:12571597 Ankyrin-B mutation causes type 4 long-QT cardiac arrhythmia ... | KEEP AS NON CORE | Summary: Ankyrin-B-dependent electrical organization influences heart rate through cardiac conduction. Reason: Human ANK2 disease/variant studies and deficient cardiomyocyte experiments connect altered channel/transporter targeting to cardiac rhythm and conduction phenotypes. Retain the integrated organ-level outcome as contextual physiology downstream of the core adaptor function, without making every source-specific ECG endpoint a separate molecular core. |
| GO:0086091 regulation of heart rate by cardiac conduction | IMP PMID:15178757 A cardiac arrhythmia syndrome caused by loss of ankyrin-B fu... | KEEP AS NON CORE | Summary: Ankyrin-B-dependent electrical organization influences heart rate through cardiac conduction. Reason: Human ANK2 disease/variant studies and deficient cardiomyocyte experiments connect altered channel/transporter targeting to cardiac rhythm and conduction phenotypes. Retain the integrated organ-level outcome as contextual physiology downstream of the core adaptor function, without making every source-specific ECG endpoint a separate molecular core. |
| GO:0086091 regulation of heart rate by cardiac conduction | IMP PMID:17242276 Defining the cellular phenotype of "ankyrin-B syndrome" vari... | KEEP AS NON CORE | Summary: Ankyrin-B-dependent electrical organization influences heart rate through cardiac conduction. Reason: Human ANK2 disease/variant studies and deficient cardiomyocyte experiments connect altered channel/transporter targeting to cardiac rhythm and conduction phenotypes. Retain the integrated organ-level outcome as contextual physiology downstream of the core adaptor function, without making every source-specific ECG endpoint a separate molecular core. |
| GO:0086091 regulation of heart rate by cardiac conduction | IMP PMID:21859974 Defects in ankyrin-based membrane protein targeting pathways... | KEEP AS NON CORE | Summary: Ankyrin-B-dependent electrical organization influences heart rate through cardiac conduction. Reason: Human ANK2 disease/variant studies and deficient cardiomyocyte experiments connect altered channel/transporter targeting to cardiac rhythm and conduction phenotypes. Retain the integrated organ-level outcome as contextual physiology downstream of the core adaptor function, without making every source-specific ECG endpoint a separate molecular core. |
| GO:0086091 regulation of heart rate by cardiac conduction | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: Ankyrin-B-dependent electrical organization influences heart rate through cardiac conduction. Reason: Human ANK2 disease/variant studies and deficient cardiomyocyte experiments connect altered channel/transporter targeting to cardiac rhythm and conduction phenotypes. Retain the integrated organ-level outcome as contextual physiology downstream of the core adaptor function, without making every source-specific ECG endpoint a separate molecular core. Propagation Review Root cause: NO FAILURE NON CORE Sources checked: UniProtKB:Q8C8R3 UNRESOLVED Original source identifier preserved. The exact historical source assertion/construct was not independently reconstructed; target-level primary corroboration or uncertainty is stated in the row reason. |
| GO:0098907 regulation of SA node cell action potential | IMP PMID:12571597 Ankyrin-B mutation causes type 4 long-QT cardiac arrhythmia ... | ACCEPT | Summary: Ankyrin-B regulates sinoatrial pacemaker-cell activity through target organization. Reason: The human sinus-node study explicitly reports ankyrin-B-dependent channel/transporter organization and abnormal pacemaking in deficient mouse cells. This independently corroborates the process across the cited disease sources, without assigning ANK2 the conductance of a pacemaker channel. |
| GO:0098907 regulation of SA node cell action potential | IMP PMID:18832177 Dysfunction in ankyrin-B-dependent ion channel and transport... | ACCEPT | Summary: Ankyrin-B regulates sinoatrial pacemaker-cell activity through target organization. Reason: The human sinus-node study explicitly reports ankyrin-B-dependent channel/transporter organization and abnormal pacemaking in deficient mouse cells. This independently corroborates the process across the cited disease sources, without assigning ANK2 the conductance of a pacemaker channel. |
| GO:0098910 regulation of atrial cardiac muscle cell action potential | IMP PMID:12571597 Ankyrin-B mutation causes type 4 long-QT cardiac arrhythmia ... | ACCEPT | Summary: Ankyrin-B-dependent targeting regulates atrial action potentials. Reason: The original disease source is incompletely inspected, but full independent PMID:21859974 directly measures atrial action-potential and current changes and provides the Cav1.3 targeting mechanism. Accept the supported biological conclusion with that independent evidence rather than relying on the historic disease label. |
| GO:0099103 channel activator activity | ISS PMID:21859974 Defects in ankyrin-based membrane protein targeting pathways... | MODIFY | Summary: The Cav1.3 experiments establish channel binding/targeting rather than direct opening. Reason: GO:0099103 requires direct channel interaction resulting in opening. Full PMID:21859974 establishes binding and membrane positioning; lower membrane channel abundance/current does not isolate opening probability. Refine to the existing transmembrane-transporter-binding activity and consolidate its support with the direct binding rows. This does not assert that ankyrin-B can never modulate gating. Propagation Review Root cause: UNRESOLVED Sources checked: UniProtKB:Q8C8R3 UNRESOLVED Original source identifier preserved. The exact historical source assertion/construct was not independently reconstructed; target-level primary corroboration or uncertainty is stated in the row reason. Proposed replacements: transmembrane transporter binding |
| GO:0099104 potassium channel activator activity | ISS GO_REF:0000024 | UNDECIDED | Summary: Potassium-channel activation needs the direction-specific gating experiment. Reason: Kir6.2 studies report ankyrin-B-related gating as well as trafficking, but the precise opening effect underlying this mouse-transferred molecular-function assertion has not been fully inspected. Increased current from more surface channels is insufficient by itself. Preserve uncertainty without denying a potentially separate direct gating mechanism. Propagation Review Root cause: UNRESOLVED Sources checked: UniProtKB:Q8C8R3 UNRESOLVED Original source identifier preserved. The exact historical source assertion/construct was not independently reconstructed; target-level primary corroboration or uncertainty is stated in the row reason. |
| GO:0140031 phosphorylation-dependent protein binding | IPI PMID:25950943 CK2-regulated schwannomin-interacting protein IQCJ-SCHIP-1 a... | UNDECIDED | Summary: The ANK2 phosphorylation-dependent pair needs full source inspection. Reason: PMID:25950943 reports CK2-regulated IQCJ-SCHIP1βankyrin-G association in its abstract. Its complete pair/construct experiments were not inspected and may assay additional ankyrins. Preserve each original partner accession and do not remove an experimental ANK2 assertion solely because the title highlights ankyrin-G. |
| GO:0140031 phosphorylation-dependent protein binding | IPI PMID:25950943 CK2-regulated schwannomin-interacting protein IQCJ-SCHIP-1 a... | UNDECIDED | Summary: The ANK2 phosphorylation-dependent pair needs full source inspection. Reason: PMID:25950943 reports CK2-regulated IQCJ-SCHIP1βankyrin-G association in its abstract. Its complete pair/construct experiments were not inspected and may assay additional ankyrins. Preserve each original partner accession and do not remove an experimental ANK2 assertion solely because the title highlights ankyrin-G. |
| GO:1903288 positive regulation of potassium ion import across plasma membrane | IMP PMID:19805355 Dual role of K ATP channel C-terminal motif in membrane targ... | UNDECIDED | Summary: The direction-specific potassium-import claim needs its assay conditions checked. Reason: The Kir6.2 source supports binding, targeting and altered channel regulation. Potassium flux direction depends on voltage and experimental conditions, and the complete experiment supporting positive import was not inspected. Neither the inward-rectifier name nor typical physiological efflux settles this source-specific assertion. |
| GO:1903288 positive regulation of potassium ion import across plasma membrane | ISS GO_REF:0000024 | UNDECIDED | Summary: The direction-specific potassium-import claim needs its assay conditions checked. Reason: The Kir6.2 source supports binding, targeting and altered channel regulation. Potassium flux direction depends on voltage and experimental conditions, and the complete experiment supporting positive import was not inspected. Neither the inward-rectifier name nor typical physiological efflux settles this source-specific assertion. Propagation Review Root cause: UNRESOLVED Sources checked: UniProtKB:Q8C8R3 UNRESOLVED Original source identifier preserved. The exact historical source assertion/construct was not independently reconstructed; target-level primary corroboration or uncertainty is stated in the row reason. |
| GO:0008017 microtubule binding | IDA PMID:32640013 Giant ankyrin-B suppresses stochastic collateral axon branch... | NEW | Summary: The giant ankyrin-B inserted domain binds and bundles microtubules. Reason: Purified fragments amplified from human 440-kDa ANK2 cDNA bind prepolymerized microtubules in cosedimentation assays; residues 1793β2070 also bundle microtubules in imaging and electron microscopy assays. The Methods identify human ENST00000264366.10, bacterial protein production and appropriate control fragments. PSK substitutions impair binding/bundling and full-length rescue of excess branching in mouse neurons. This is a direct molecular activity of the tested giant-domain sequence, not an inference from the protein being necessary for neuronal development. The exact construct is described rather than guessing a correspondence to a current UniProt isoform accession. No plus-end, minus-end or motor activity is inferred. Supporting Evidence: PMID:32640013 Taken together, gAnkB contains a stretch of amino acids (1793β2070) that avidly bind and bundle MTs in vitro. |
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Download this section (compressed HTML)Q: Which original experiments support the highly specific cardiac cell-to-cell communication, atrial-septum and direction-specific ion-flux assertions, and which ANK2 isoforms/constructs were assayed?
Q: Can the original pair records resolve ANK2-specific interactions in ankyrin-G-centered and large interaction-network papers without substituting title or abstract emphasis for the curator-reviewed full evidence?
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