CACNA1B encodes human CaV2.2 alpha1B, the pore-forming subunit of an N-type, high-voltage-activated calcium channel. All 29 normal seeded assertions were assessed, preserving the 30 raw GOA records represented by them: the two assigner/date records for the PPM1A interaction have the same scientific source key and remain one seeded assertion. Both named products, Alpha-1B-1/Q00975-1 and Alpha-1B-2/Q00975-2, retain their exact identities and sequence note. No new annotation is proposed.
The decisions are 18 ACCEPT, 4 KEEP_AS_NON_CORE, 6 MODIFY and 1 UNDECIDED. The modifications refine broad channel activity to the existing high-voltage activity, two broad transport assignments to the existing calcium-import process, two broad membrane assignments to plasma membrane, and one generic interaction to protein-phosphatase binding. One integrated core combines the alpha1B pore, calcium import and synaptic transmission. Calcium binding, phosphorylation-dependent regulation and protein interactions are features of this channel mechanism rather than additional independent cores.
The complete normal abstract of PMID:1321501(https://pubmed.ncbi.nlm.nih.gov/1321501/) describes human alpha1B-1 coexpression with human beta2 and alpha2b in HEK293 cells. The resulting current is omega-conotoxin-sensitive and dihydropyridine-insensitive. The experiment supports the pore function and channel-complex membership. Its requirement for beta2 and modulation by alpha2b concern that reconstitution; they do not establish one invariant auxiliary-subunit composition in every neuron. The abstract also identifies the two alpha1B sequence forms. The full paper, traces and all isoform comparisons were not inspected.
PMID:34234349(https://pubmed.ncbi.nlm.nih.gov/34234349/) provides complementary structural evidence. The preserved canonical cache contains only the abstract. Selected unique Results and Methods were also read in the authenticated fuller normal-fetch variant, without replacing that cache. Full-length human Q00975-1 was coexpressed with human alpha2delta1 and beta3 in HEK293F and purified for cryo-EM with or without ziconotide. The source resolves voltage-sensor/pore architecture and calcium coordination by the selectivity-filter glutamates. This supports the channel mechanism and broad calcium interaction; it does not establish a separate soluble calcium-sensor function, a particular EF-hand affinity, or endogenous localization from a detergent preparation. Most of the C-terminal cytosolic region was unresolved in the structure despite expression of the full-length construct. Images, maps and supplementary material were not independently examined. Every YAML quotation from this reference is restricted to its canonical abstract.
The complete cached Reactome event places calcium influx before transmitter-vesicle fusion. The GOA compartment assertion and independent target evidence support plasma membrane; the cached event summary itself supplies pathway context rather than a separate explicit compartment field. Alpha1B performs the calcium-conduction step. It does not perform every downstream fusion reaction. The promoter experiments in PMID:9030575 support neuronal expression; their synaptic-transmission TAS assertion is retained with independent functional evidence, without describing the promoter study as a direct release assay.
The complete PMID:11438518 abstract directly reports binding of RIM C2 domains to alpha1B. The source remains abstract-only, so detailed organism/construct conditions and intact-channel versus fragment comparisons were not independently resolved. RIM's scaffold function is not transferred to the channel.
Actual Methods and Results in PMID:15728831(https://pubmed.ncbi.nlm.nih.gov/15728831/) establish binding of the alpha1B intracellular C terminus to the PPM1A/PP2C-alpha phosphatase. Human alpha1B bait, rat-brain prey, recombinant pulldown and HEK293 coimmunoprecipitation are distinguished from additional native rat-brain evidence. The exact xenologous partner P20650 is preserved. GO:0019903 protein phosphatase binding, under phosphatase/enzyme binding, provides a supported refinement of the generic binding annotation. The loop phosphorylation/dephosphorylation experiments identify alpha1B as a substrate and associated regulatory target, not a phosphatase or phosphatase activator. No separate binding core is added.
PMID:20195357 supplies a human mRNA-display interaction-region screen. The complete abstract and selected methodological narrative were inspected, including fragment-based screening and human brain prey. The exact CACNA1B–RXRB supplemental row and its individual verification status were not inspected. Its literal Q00975–P28702 curated GOA/UniProt edge is retained with curator deference and that access limitation. The dataset's overall verification rate is not a claim that this particular edge was individually verified, and the association is not evidence of channel transcription-factor activity or nuclear localization.
The two retained generic-binding rows follow the standing project instruction: supported generic interactions are retained as non-core when no justified finer function is assigned. The PPM1A row instead receives a source-supported specific replacement.
The complete abstract and available indexed primary Results/conclusion of PMID:23376566(https://pubmed.ncbi.nlm.nih.gov/23376566/) describe synthetic amyloid-beta globulomer modulation of recombinant N/PQ currents, plus protection of slice-culture synaptic function by channel blockers. N-type current activation shifted toward more negative voltages; nonaggregated peptide had no effect. These findings support channel activity, synaptic modulation and a contextual non-core response to amyloid-beta.
GO:0001540 requires binding to amyloid-beta. No target physical-binding assay was established in the inspected material, and the full article and supplements were inaccessible. The original IC assertion remains UNDECIDED rather than being treated as false. Functional current modulation is not by itself proof of direct binding, and an unidentified intermediary is not asserted as fact. The core therefore describes established calcium conduction rather than an endogenous amyloid-receptor role.
The complete normal abstract of PMID:25296916 reports WT/R1389H electrophysiology: lower open-channel current with preserved selectivity and voltage-dependent activation/inactivation. That remains direct evidence for the channel activity. The proposed R1389H myoclonus-dystonia association is a separate claim, now assessed against the normally cached PMID:26157024(https://pubmed.ncbi.nlm.nih.gov/26157024/). Its complete abstract and unique Introduction, Results, Discussion and Materials and Methods were read. The study found the variant in one of 520 cases and one of 489 controls, and in none of 146 familial probands. Cases underwent exon-28 Sanger sequencing; the control comparison used whole-exome data. The authors did not support causal association of this specific variant with the disorder. The original disease finding is therefore explicitly DISPUTED, with the negative source attributed within its finding review. This does not invalidate the reported channel-current measurements, settle all CACNA1B-related disease mechanisms, or provide a current clinical classification. Supplementary chromatograms and images were not inspected.
The existing PAINT nodes and donor lists remain exact. Direct human channel evidence independently supports complex membership, high-voltage channel activity and calcium import. A target self-source is legitimate descendant experimental grounding; a short or phylogenetically broad donor list does not invalidate a PAINT inference. Exact node placement and alignment were not independently reconstructed. The exact ISS donor Q02294 was verified as rat Cacna1b using the indexed official UniProt record; its original exocytosis experiment was not independently re-read. Curated somatic and terminal function supports retention with this boundary, not a claim of a new human localization assay.
Official GO:0008331 includes N-type high-voltage channels. GO:0098703 describes calcium entry from outside the cell into cytosol across plasma membrane. The selected replacements refine existing target activities/processes and do not add ancestor/descendant NEW redundancy. The local GO-CAM index had no Q00975/CACNA1B hit at review time; this is only a local inventory observation. No pathway-completeness argument was used to manufacture a process annotation.
All nine PMID identities and complete abstracts were checked. Canonical PMID:15728831 and PMID:20195357 bodies support the selected additional reading; canonical PMID:34234349 remains abstract-only with explicitly supplemental fuller-source paraphrase. The newly added PMID:26157024 supplies full XML cohort evidence; the other remaining PMID caches are abstract-only. Normal source files, existing caches and quarantined family exports remain unchanged. A single normal Falcon invocation with the configured perplexity-lite fallback failed because of DNS errors; no provider output was created. These notes are manual primary-source research, not provider-generated research.
Eleven short YAML quotation entries are verbatim in the normal canonical caches and total at most 23 words per source including reuse. The independent three-row binding consultation was integrated with an explicit protein-phosphatase-binding refinement, and a separate synthesis consultation checks the one-core description. These bounded consultations are distinct from the whole scientific peer review.
Full normal validation, including source GOA consistency, references, verbatim quotations and authored ontology terms, passed with two expected generic-binding policy warnings and no errors. DRAFT records those advisories while preserving the explicit unresolved amyloid-binding assertion.
The added cohort reference and the corresponding disputed-finding assessment leave all 29 annotation decisions, source fields, both products, the description and the single core unchanged. The original 15 reference identities are preserved. The negative evidence is attached to the disease finding rather than added as positive support for channel activity.
The independently approved review passed full normal canonical validation and status reporting, retaining DRAFT with two standing-policy binding advisories. All 29 source assertions, both named products and source-cache bytes are preserved. The standard CREATE history record passed history validation.
PMID:30982612(https://pubmed.ncbi.nlm.nih.gov/30982612/) supplies the human evidence behind UniProt's current autosomal recessive neurodevelopmental disorder with seizures and non-epileptic hyperkinetic movements (NEDNEH; MIM:618497). The study reports six affected children from three unrelated families with biallelic truncating or splice-site CACNA1B variants and a progressive developmental and epileptic encephalopathy with severe hyperkinetic movements. This disease evidence is distinct from the heterozygous R1389H myoclonus-dystonia claim contested by PMID:26157024. The earlier negative association finding does not invalidate this recessive syndrome.
The complete available abstract and HTML Main Text narrative were read, including the case descriptions, genetic methodology and segregation findings, and the mechanistic discussion. The source predicts nonsense-mediated decay or protein truncation and postulates impaired calcium influx and synaptic transmission. It does not establish those variant effects with direct electrophysiology in the inspected narrative. Table cells, images, supplementary files and the full bibliography are absent from this extraction and were not read. The Arg383/Arg380 inconsistency within the main narrative is not resolved here; exact variant numbering is unnecessary for this functional summary and is not copied.
The description now includes the recessive syndrome and labels the channel mechanism as proposed. The UniProt reference assessment explicitly identifies this newly assessed disease evidence instead of implying that the earlier review had already covered it. All 29 source assertions and actions, both named products, the pore-function core and previous reference identities remain intact. The sole annotation-reason addition concerns the neuronal-cell-body evidence boundary; no new annotation is proposed from clinical necessity.
The paper describes expression across CNS regions and points to Figure S4. The primary institutional supplement's indexed Figure S4 legend identifies BRAINEAC exon-array mRNA measurements from ten adult brain regions in 134 control individuals. That is regional tissue-expression evidence, not endogenous neuronal-cell-body protein localization. Only the indexed legend was inspected, not the figure or full supplement. GO:0043025 therefore remains ACCEPT on its original phylogenetic/curated-distribution basis, with the human subcellular protein-assay access limit retained. The new disease reference is not inserted as positive support for that narrower location claim.
The new reference includes one exact 19-word clinical finding anchor. All previous quotation entries are unchanged; no source exceeds 25 quoted words including reuse. Earlier source-access notes describe their respective checkpoints and are not claims that this paper had already been read then.
The independently approved candidate passed full normal canonical validation, status reporting, targeted rendering and standard EDIT history validation. DRAFT retains two expected standing-policy binding advisories. All 29 source assertions and actions, both products, the core, prior references, source files and history are preserved. See the follow-up history.