The genuine seed7 normal fetch supplied human ANK2/Q01484, 129 raw GOA rows and 128 seeded source assertions after the ordinary exact-duplicate collapse. All four alternative products are preserved: displayed giant Q01484-4 and Q01484-2, Q01484-5 and Q01484-7. The source annotations do not contain isoform flags; a particular experimental construct does not justify inventing one. Exact original files are retained under tmp/ANK2-initial/baseline/. Root imported the verified seed and seventeen absent source caches; existing differing caches were preserved.
One configured ordinary deep-research invocation reached the installed client. Falcon authentication failed and the Perplexity fallback failed DNS; neither produced a report. Earlier tool-installation failures are not counted as provider attempts. These are manually authored notes, not provider output. A single six-PMID normal batch timed out after ninety seconds with zero files. This is one batch outcome, not evidence of six completed individual failures. The fixed source28 recovery request retains the original receipt and primary identity/read-scope assessment. No publication text has been authored or existing cache replaced.
The review is in progress. The source census is 22 original PMID records, eight Reactome records and eight GO references. Six additional primary papers have been identified for source closure. Reading scopes below distinguish actual full-body inspection, selected original sections, abstract-only records and partial extraction. A full_text_available: true flag alone is not proof of a complete paper.
Ankyrin-B is a modular cytoskeletal adaptor, with an N-terminal ankyrin-repeat membrane-target binding region, spectrin-binding ZU5-based architecture and regulatory regions. It organizes transporters and channels at appropriate membrane domains, rather than acting as the ion transporter or pump. In cardiac cells, NCX1, Na/K-ATPase, IP3 receptors and Cav1.3 are important targets. Skeletal-muscle experiments distinguish ankyrin-B-dependent delivery of dystrophin from ankyrin-G-dependent retention. Neuronal giant ankyrin-B has a large insertion with additional microtubule-associated functions; those findings are not silently generalized to all four human splice products. PMID:15178757; PMID:15262991; PMID:17178715; PMID:19109891; PMID:21859974
The historical long-QT label does not establish a uniform QT phenotype for all ANK2 variants. The original papers describe broader arrhythmia phenotypes and variable cellular effects. Clinical necessity, altered protein abundance and an electrophysiological output are kept separate from a demonstrated direct molecular activity. PMID:12571597; PMID:15178757; PMID:17242276
The complete cached body of PMID:15178757 was read. Human 220-kDa GFP-ankyrin-B constructs rescued defects in neonatal mouse cardiomyocytes, including localization/levels of NCX, Na/K-ATPase and IP3 receptors, calcium handling and contraction. This is human-protein evidence in a mouse cellular host. Mature-protein targeting/stability is not automatically increased gene-expression biosynthesis. Adult heterozygous ventricular findings differ from earlier neonatal null experiments; preserved Nav1.5 localization in this setting does not justify an unlimited claim that ankyrin-B never affects ventricular physiology.
PMID:15262991 is abstract-only. It directly reports ankyrin-B–β2-spectrin binding and β2-spectrin targeting to a compartment overlying the M-line in neonatal cardiomyocytes. Spectrin-binding mutants separate β2-spectrin targeting from other ankyrin-B functions. The compartment was distinct from several organelles in this experiment; that contextual observation does not negate endosomal or mitochondrial ankyrin-B in other cells. PMID:17178715 is also abstract-only and supports direct NCX1 binding, membrane targeting and posttranslational stability. The six original cardiac papers cached as abstracts retain those access limits: 12571597, 15262991, 17178715, 17242276, 18832177 and 19098452.
The complete cached main body of PMID:18782775 was read. The study includes human heart transcripts, a human obscurin C-terminal construct (6148–6460), ankyrin-B regulatory constructs with exon43′, purified binding, heart co-immunoprecipitation and cardiomyocyte localization. Ankyrin-B binds obscurin at the M-line and helps localize B56α/PP2A there. The paper explicitly distinguishes the ankyrin-binding 800-kDa obscurin isoform from 900-kDa and smaller kinase products. This is the substantive reason to refine the protein-kinase-binding row toward cytoskeletal adaptor activity. Binding a noncatalytic domain of an actual kinase could still count as kinase binding; that general possibility is not the issue here. An independent ankyrin-family consultation agreed with the isoform-specific interpretation after reading these sections.
PMID:18832177 reports human sinus-node disease and abnormal pacemaking in ankyrin-B-deficient mice, but the accessible abstract does not expose the atrial-septum developmental assay. That particular experimental assertion remains unresolved rather than being removed. PMID:19007774 explicitly studies rods from humans, mice and frogs, supporting the inner-segment membrane context. PMID:19098452 summarizes the cardiac targeting mechanism; its abstract is not a substitute for every original source-specific electrophysiology experiment.
PMID:19109891 is abstract-only and distinguishes dystrophin transport to the sarcolemma by ankyrin-B from its retention by ankyrin-G; the source partner isoform P11532-5 remains intact. PMID:19805355 and PMID:20610380 are canonical abstract-only records. They support Kir6.2 binding and trafficking and report gating effects. Targeted indexed original Results were consulted, but direction-specific potassium import or channel-opening conclusions still require matching the precise experiment, voltage conditions and constructs.
Main Methods, Results and Discussion of PMID:21859974 were read from the full normal cache. Human atrial material and mouse cardiomyocytes show ankyrin-B-related Cav1.3 targeting and atrial electrical changes. Direct binding is mapped to the Cav1.3 C-terminal region, including a required 2175–2198 motif. Reduced surface channel abundance and current do not alone establish direct channel opening. Original partner Q99246 is mouse Cacna1d and P27732 is rat Cacna1d; these partner identities are not rewritten as human. The source does not turn plasma-membrane calcium influx into a direct sarcoplasmic-reticulum release assay.
PMID:15611082 and PMID:25950943 foreground ankyrin-G in their titles/abstracts. The former describes human RhBG in canine MDCK cells; the latter describes phosphorylation-dependent IQCJ-SCHIP1–AnkG interactions. Neither complete original article was inspected. Their ANK2 experimental assertions are not removed on a title/paralog argument: a full paper can assay multiple ankyrins. The exact ANK2 pair/construct remains to be checked.
PMID:17474147 is an abstract-only SH3 interaction survey; the exact ANK2–GRB2 pair record and assay validation are unavailable. PMID:20489164 has an unchanged canonical abstract; a longer normal recovery candidate was consulted read-only, without overwriting it or claiming complete inspection. EHD3-associated cardiac targeting is biologically relevant, but the specific physical pair and its mechanistic scope must remain distinct.
Relevant main experimental sections of PMID:26949739 were read. Targeted co-immunoprecipitation confirms ACOT7 in ANK2-purified lysates from differentiated SH-SY5Y cells. This is a real observed association, but generic protein binding does not describe an established ANK2 biochemical function with ACOT7; no acyl-CoA-metabolic activity is inferred for ankyrin-B. PMID:30021884 has a true full-text flag but the actual cached extraction contains only Abstract and Discussion, without the pair data. It does not expose the ANK2–RRBP1 record.
Relevant main sections of PMID:36950384 were read. Native induced-neuron IP-MS and giant-ANK2 perturbation results are distinguished from pairwise direct binding. The ANK2–DYNC1H1 and ANK2–RRBP1 supplementary pair records were not inspected. Generic-binding rows whose exact experimental support is inaccessible remain UNDECIDED, even though a less generic molecular term would be desirable. No absence of a pair from the article body is treated as proof that curators made a wrong-gene attribution.
PMID:32353364 is abstract-only, but the primary structural entry 6M3Q independently identifies human ANK2/Q01484 with mouse β4-spectrin/E9PX29. This supports spectrin binding with the species boundary explicit. RCSB 6M3Q
Relevant Methods, Results and Discussion of PMID:21177872 were inspected. Recombinant ankyrin-B repeats/peptides are substrates of FIH-mediated hydroxylation. Much of the erythrocyte work concerns ankyrin-R, which must not be reassigned to ankyrin-B. Binding the hydroxylase does not make ANK2 a hydroxylase or establish active participation in the hydroxylation reaction.
PMID:25533844: official identity, abstract and figure legends, plus targeted indexed original discussion, were read. Mouse-neuron experiments connect ankyrin-B, PI3P and dynactin-p62 to organelle transport; loss of ankyrin-B did not disrupt the measured periodic spectrin-actin rings in that setting. This helps separate cargo coupling from a claim that every cytoskeletal structure depends on ANK2. PubMed
PMID:27718357: identity, abstract and targeted indexed localization Results were inspected. Ankyrin-B occupies early and recycling endosomal compartments, with more restricted lysosomal and mitochondrial signals; recruitment of RabGAP1L is an adaptor mechanism, not intrinsic Rab-GAP catalysis. Full normal source recovery remains pending. Primary article
PMID:25362471: identity, abstract and targeted main Results/Discussion were read. Schwann-cell ankyrin-B and oligodendrocyte ankyrin-G must be separated; combined CNS loss and compensatory ankyrin-B cannot be compressed into a claim of universally essential PNS ankyrin-B. The structural glial contribution can remain meaningful despite redundancy. The complete Methods and supplements have not yet been inspected. Primary article
PMID:12949909: official PubMed identity and complete abstract were read. Rat cerebellar cultures lose the giant ankyrin-B signal after methylmercury exposure, with the protein proposed as an early marker. A protein being depleted by an insult is not sufficient evidence that the protein actively performs a response step. The exact rat donor annotation and original full article remain uninspected. PubMed
PMID:32640013: identity, abstract, selected original Results and the human giant-construct Methods were inspected. A bipartite giant-insertion motif binds/bundles microtubules, and binding-defective mutants fail to rescue excess branching. This supports an isoform-specific structural mechanism, with no claim to complete supplementary review. PMID:34812142: identity and abstract were inspected; full Methods/Results remain unread. Its Sema3A/L1CAM/NRP1 findings need their own experimental scope. 2020 primary article; 2021 primary article
Official GO definitions distinguish protein-kinase binding from binding any product of a kinase-containing locus, direct channel activation from increased channel abundance, and gene-expression biosynthesis from mature-protein stabilization. Existing source identifiers remain unchanged. Refinements use terms already in the seed; no NEW process is proposed from disease necessity or perceived annotation gaps.
The actual local PAINT table interpro/panther/PTHR24123/PTHR24123-paint.tsv contains IBD assertions at PTN002380879 for plasma membrane, neuron projection, cytoskeletal adaptor activity, spectrin binding, transmembrane transporter binding and protein localization to plasma membrane. Their taxon is 33213. ANK2 appears as its own experimentally grounded descendant seed for several terms, which is legitimate. The family tree/MSA and historical donor experiments have not all been reconstructed. Node support is real, while its precise evolutionary placement is not re-adjudicated from donor count.
All eight Reactome summaries were inspected. They support a cytosolic ankyrin pool in trafficking contexts. Membership in a COPI/ARF/SNARE reaction context does not make ANK2 an ARF GAP, SNARE or coat enzyme. The core synthesis will center on cytoskeletal adaptor activity and directly supported protein positioning; contextual tissue outcomes and unresolved pair records remain distinguishable.
Independent consultation clarification (2026-09-27): all 128 draft rationales, the core and notes were reviewed. Row 95 now grounds the calcium-transport refinement in the demonstrated targeting/regulatory role and the scope of PMID:19098452; a structural scaffold may participate in a process without catalysis. The accessible 19098452 abstract also directly corroborates the accepted calcium-release regulation in row 85. No action, source object, or core term changed. The six additional Source28 records remain pending actual cache inspection.
The earlier six-source recovery boundary is now closed. All six exact normal source records were inspected in the verified Source28 staging area and then imported by the coordinator without overwriting an existing cache. The final source census is 28 PMID records, eight Reactome records and eight GO references. Five new PMID records contain full-text extractions; PMID:12949909 remains abstract-only. The read scopes below describe actual inspected sections, not a claim to have read every method, supplement or video merely because full text was recovered. Original PMID/title/DOI identities were reconciled with primary-source identity checks and the actual recovered records.
Organelle localization and trafficking. The recovered PMID:27718357 Results, figure legends and DNA-construct Methods establish preferential 220-kDa AnkB localization to Rab5-positive early endosomes, partial overlap with Rab11-positive recycling endosomes and LAMP1-positive lysosomes, and restricted mitochondrial-end puncta in mouse embryonic fibroblasts. The experiment expresses AnkB-mCherry in an AnkB-null background because excess expression in ordinary fibroblasts was toxic. It supports a compartment-associated pool, not matrix residence, a uniform mitochondrial coat, or identical localization of all human splice products. Exact source wording is: “Moreover, we detected a restricted association of AnkB-mCherry with puncta at mitochondria ends.” These observations close the eight original UniProt/mouse mitochondrial, lysosomal, early-endosomal and recycling-endosomal assertions as ACCEPT. The exact historical donor/rule assertions remain unreconstructed; current experimental corroboration and historical propagation provenance are distinct judgments.
Targeted organelle transport, dynactin/p62 recruitment, PI3P-binding and PIK3C3 Results, plus the complete Constructs subsection of PMID:25533844, independently support 220-kDa AnkB-associated cargo transport in mouse hippocampal neurons. Rab5 endosomes, LAMP1 lysosomes and restricted mitochondrial contacts are experimentally observed. Purified human S966–T1535 ZU5-containing protein binds PI3P; wild-type versus p62-binding-defective constructs test coupling to dynactin. The human fragment and mouse cellular host are recorded separately. AnkB does not supply the motor's ATPase activity. The remaining Methods and video data were not comprehensively inspected.
Adaptor activity beyond the cytoskeletal subclass. PMID:27718357 identifies mouse RabGAP1L with a human AnkB death-domain bait and tests cellular binding, binding-site disruption and RabGAP1L recruitment. The source concludes: “Together, these results reveal a new protein-protein interaction between AnkB and RabGAP1L that recruits RabGAP1L to PI3P-positive organelles.” RabGAP1L performs the GAP chemistry. These results, together with the independent receptor-organizing mechanism below, justify retaining the original broad protein-macromolecule adaptor activity assertion as ACCEPT instead of narrowing every adaptor role to cytoskeletal anchoring. The review retains one primary cytoskeletal-adaptor core and describes the parallel membrane-organizing activity explicitly; it does not manufacture a new enzyme or process annotation.
Glial paranodes. Targeted localization, single-knockout, double-knockout, NF155-interaction and splice-product Results plus animal Methods of PMID:25362471 distinguish glial 220-kDa AnkB from giant neuronal AnkB and oligodendrocyte AnkG. AnkB loss alone leaves PNS paranodes intact, but combined CNS AnkB/AnkG loss worsens the AnkG assembly phenotype. The source states: “Thus, AnkB can partially compensate for the loss of AnkG in oligodendrocytes.” NF155 coassociation adds structural context to the perturbation evidence. The existing paranodal-assembly assertion is retained as KEEP_AS_NON_CORE, without claiming universal AnkB necessity or assigning AnkG-only assays to AnkB. Its exact historical rat donor assertion remains unresolved. Other Methods and supplements were not comprehensively read.
Methylmercury. The complete normal abstract of PMID:12949909 describes loss of 440-kDa AnkB in rat cerebellar cultures as an early degeneration marker. It does not establish that AnkB performs the toxic-response process. The original full article and exact historical rat donor assertion remain unavailable, so the source-specific response annotation stays UNDECIDED. Recovery of a complete abstract is not equivalent to recovering the complete article.
Two giant-isoform mechanisms. Targeted purified-protein binding/bundling Results, repeat-mutant rescue, Discussion and the cloning/expression/purification Methods subsection of PMID:32640013 identify an explicitly human full-length giant construct derived from ENST00000264366.10. Purified human giant-domain fragments interact with porcine-brain tubulin, and wild-type versus microtubule-binding-defective PSK constructs distinguish rescue of excess branching in mouse neurons. This directly supports giant-insertion-dependent microtubule binding and organization; it is not assigned to every 220-kDa product. Other Methods and supplementary data were not comprehensively inspected.
In PMID:34812142, targeted Results/legends, a Discussion paragraph and plasmid Methods, supplemented by an independent focused read of key resources and assay Methods, distinguish giant AnkB-dependent Sema3A growth-cone collapse from the older microtubule mechanism. Mouse cortical-neuron knockout and rescue experiments show a selective giant-isoform requirement, whereas EphrinA5 responses persist. AnkB supports surface L1CAM–Nrp1 receptor organization. Surface biotinylation and proximity ligation support localization and proximity; PLA does not establish purified binary Nrp1 binding. Crucially, betaII-spectrin-deficient neurons still respond, and the microtubule-binding-defective PSK giant construct rescues Sema3A collapse. Thus this receptor-organizing mechanism operates independently of the spectrin/microtubule links tested here. Cofilin signaling does not make AnkB a kinase or actin-severing enzyme. The paper points to prior construct sources; human HEK293T host cells alone do not prove that every tested construct is human. No exhaustive whole-paper or supplement read is claimed.
The final review preserves all 128 original source assertions, four alternative products and their qualifiers and source identifiers. Actions are 75 ACCEPT, 33 UNDECIDED, 10 MODIFY, 1 REMOVE and 9 KEEP_AS_NON_CORE, with no NEW assertions. Remaining undecided judgments reflect specific inaccessible experiments, pair records or unresolved transfer claims, rather than an unfinished normal-source recovery request. The complete draft had independent all-row consultation before this closure; the changed source-specific decisions and synthesis receive a final bounded consultation. The two known validator advisories concern the official current “cytoskeletal adaptor activity” label versus the local older label cache, and deliberately different actions on distinct source assertions for calcium-release regulation.
The completed source reading now supports replacing the stale pending-source reason for the existing nervous-system-development annotation with KEEP_AS_NON_CORE. PMID:32640013 and PMID:34812142 corroborate neuronal architecture through experimentally separable giant-isoform mechanisms; the exact historical rat donor record remains unreconstructed. This updates an existing assertion, without adding a new developmental process.
GO:0008017 microtubule binding was checked in the official GO browser, including its tubulin-binding parent. It describes a separate molecular activity from GO:0008093 cytoskeletal adaptor activity. No specific tubulin/microtubule binding row was present; the restored proposal is not an ancestor/descendant duplicate of a retained specific activity. Generic interaction rows retain their distinct partner-level decisions.
The original PMID:32640013 article Results, Figures 2–6 and cloning/purification Methods establish human giant ANK2 fragments binding and bundling prepolymerized microtubules. Methods specify ENST00000264366.10 and distinguish rat giant ankyrin-G comparators. Human giant-ANK2 fragment 1793–2070 cosediments with microtubules and promotes bundles, with control fragments/GFP and PSK-mutant comparisons. Human full-length rescue was tested in mouse neurons; those cellular findings are not mislabeled as human endogenous-neuron experiments. The exact current UniProt isoform mapping has not been independently sequence-matched, so the annotation describes the tested giant construct explicitly instead of guessing an accession. A separate microtubule-binding NEW molecular-function row and core now record the activity already discussed in the review. No new process is proposed.
All 128 original source objects and four alternative products are preserved. Publication caches, original normal seed files, and the published history record are unchanged. Validation, rendering and independent follow-up consultation are recorded after the revision.