CALM3 GOA file fetched on 2026-03-19 contains no literal ISO evidence-code rows, but it does contain multiple transferred annotations (IBA and IEA). I reviewed those in the spirit of [projects/ISO.md] by asking whether a term is safe to transfer across the human calmodulin paralogs.CALM1, CALM2, and CALM3, and all three encode an identical 149 aa calmodulin polypeptide PMID:27516456 PMID:31454269.CALM3 was reported to be more highly transcribed than CALM1 or CALM2 PMID:9681195.CALM3: defective calmodulin regulation of RyR2 increases spontaneous calcium release events PMID:20226167 and the CALM3 A103V mutation promotes arrhythmogenic calcium waves and sparks PMID:27516456.CALM3 also has direct human disease evidence for impaired L-type calcium channel regulation and action potential phenotypes in calmodulinopathy PMID:31454269.CALM3 from CALM1 / CALM2: synaptic localizations, myelin-associated terms, sperm terms, and specialized membrane-trafficking terms likely reflect cell-type context layered on top of the same calmodulin protein sequence rather than a CALM3-specific biochemical innovation PMID:9681195.substantia nigra development is based on proteomic detection in diseased tissue rather than developmental perturbation PMID:22926577.protein binding annotations are not informative for calmodulin and should not be favored when more specific regulator/binding terms are available.CALM1, CALM2, and CALM3 all show the same 149 aa sequence summary and I found no ALTERNATIVE PRODUCTS block in these local records, so there is no isoform-specific caveat comparable to the splice-isoform project genes [file:human/CALM1/CALM1-uniprot.txt "SQ SEQUENCE 149 AA"] [file:human/CALM2/CALM2-uniprot.txt "SQ SEQUENCE 149 AA"] [file:human/CALM3/CALM3-uniprot.txt "SQ SEQUENCE 149 AA"].The YAML description field was revised to keep it as a standalone biological summary. Project-specific curation framing moved here instead.
This entry supersedes the earlier interpretive statements where they conflict; the dated journal above remains unchanged. The normal source seeder reconstructs 115 distinct assertions from 115 raw records, compared with 111 earlier review rows. Four partner-specific assertions were restored: two additional myelin-basic-protein partners, IQGAP3, and CaMKII-delta. They are restored source assertions, not NEW annotations. Source GO identifiers, evidence, original references, relation qualifiers, exact partner/donor identifiers and product identity are preserved. All records concern P0DP25; the local CALM3 record does not provide an alternative-products block. CALM1/2/3 are different genes, not three CALM3 isoforms.
The existing Falcon report is provider-authored orientation. Its main biological narrative was read, not every table/reference independently verified; it has not been rewritten or represented as a new research attempt. Source-specific judgments instead use the immutable canonical publications, reaction summaries and UniProt record. Many of the experiments were already read during the immediately preceding CALM1 review; reuse of that reading is explicitly recorded in the source-reuse map. Matching biochemical evidence is not treated as matching gene-specific clinical evidence.
CALM1, CALM2 and CALM3 share the canonical calmodulin sequence. This supports transfer of its intrinsic calcium-sensing and target-regulatory biochemistry, but does not establish identical transcription, tissue distribution, dosage or disease variants. PMID:9681195 directly compares transcription in proliferating human teratoma cells; its CALM3 advantage is not a general expression ranking across tissues. The abstract is complete, while the full experimental paper was unavailable.
PMID:23040497 concerns CALM1 variants. Its mature-protein N53I/N97S notation corresponds to UniProt precursor N54I/N98S because the initiator methionine is removed. These patient variants are not relabeled CALM3. PMID:27516456 directly identifies CALM3-A103V and compares its channel/calcium effects with CALM1 variants. PMID:31454269 distinguishes CALM1-E141V from CALM3-E141K; both mosaic pedigrees involve CALM3, including D130G. The recombinant affinity and overexpression cardiomyocyte experiments are distinguished from clinical gene attribution. These caches contain complete abstracts but only selected full-text narrative; detailed supplemental Methods, figures and target tables were not claimed as read.
The related PMID:26969752 cache and PubMed-formatted abstract report different cohort counts. No prevalence or patient-count assertion is made here. Variant labels are retained in their cited convention rather than silently shifted between mature and precursor numbering.
The kinase unit is supported by human CaMKII/calmodulin structures and solution-binding experiments in PMID:20668654. Complete unique Results and Methods were read, alongside the complete abstract. Calmodulin binding relieves autoinhibition; CaMKII performs phosphate transfer. The construct numbering reported by the paper is not a new human product. The structural study is not a direct neuronal long-term-potentiation experiment, so the existing pathway row is retained as a contextual assertion.
The calcineurin unit is supported by PMID:8631777: engineered human calmodulin mutants restrict calcium-induced opening, lose target activation and regain regulatory activity after reduction. This establishes calmodulin's own phosphatase-activator work, not phosphatase catalysis. Only the complete abstract was available.
The channel unit combines binding and calcium sensing with calcium-dependent channel regulation. The mouse RyR2-R2474S experiment in PMID:20226167 mutates the channel, not a human CALM gene. Human CALM3 variant experiments independently support its cardiac relevance. PMID:22067155 provides RyR2-directed FRET and Z-line association in ventricular myocytes; all available cached Introduction/Discussion were read, with detailed Methods/Results absent. Channel-associated calmodulin is a regulator rather than a pore or sarcomeric structural protein.
The existing nitric-oxide-synthase regulator assertion is supported independently of its rodent transfer by the complete cached human event Reactome:R-HSA-202110, in which calmodulin relieves caveolin inhibition of eNOS. The official GO:0030235 definition describes binding and modulation of NOS and includes NOS binding. Its own regulatory activity is distinct from kinase, phosphatase and channel regulation. NOS performs nitric-oxide synthesis. The linked primary papers and complete structured Reactome participant/compartment graph were not inspected; no new process or CALM3-specific endothelial expression assertion is proposed. Official term record: https://amigo.geneontology.org/amigo/term/GO:0030235 .
The complete cached human Reactome:R-HSA-9956602, R-HSA-9956624 and R-HSA-9956667 narratives describe CaM/OspC3/CASP4 assembly. Calmodulin binds and assists the assembly; OspC3 performs ADP-riboxanation. These summaries corroborate a cytosolic pool without transferring bacterial catalysis or manufacturing an infection-process annotation.
Binding is evaluated for the literal source partner. Direct protein-4.1, channel, CaMKII and edema-factor interactions permit evidence-supported refinements. The edema-factor structure in PMID:11807546 establishes bacterial cyclase activation, not a mammalian GPCR pathway. The separate mu-opioid-receptor experiment in PMID:10899953 supports a contextual GPCR regulatory role. CP110 binding-defective mutants in PMID:16760425 connect the interaction with cytokinesis, but that context is not promoted to a universal core activity.
The exact myelin-basic-protein partners survive. The official erratum to PMID:19855925 corrects Figure 5 panels and an axis unit; correction prose was read in the prior bounded consultation, but corrected images were not reanalyzed and no affected quantitative circular-dichroism inference is made. See https://link.springer.com/article/10.1007/s00726-010-0583-6 . The IQGAP2/IQGAP3 peptide assays support the curated interactions without conferring GTPase activity on calmodulin.
The LYST target interaction and original tau target assay remain unresolved in the accessible sources. PMID:3111527 is intrinsically truncated. PMID:22926577 describes adult substantia-nigra proteomics in its abstract; this alone neither proves development nor warrants rejecting an experimental annotation whose full evidence was unavailable. The earlier journal's proposed removal is therefore superseded by source-specific uncertainty. Supported generic interactions are retained as non-core where no justified finer function is available, following the project's explicit binding policy; biological review reasons describe the evidence rather than debate that policy.
The exact PAINT IBD assertions were inspected in the cached calmodulin family export: PTN000549682, PTN008588804, PTN008588806 and PTN008588809 cover the eight seeded IBA rows. The complete tree/MSA and every descendant experiment were not reanalyzed. Short donor lists and human target self-evidence are not treated as weak or circular support. Rodent-derived tissue and trafficking contexts are separately traced and assessed in the bounded consultation; identical protein sequence alone is not proof of CALM3-specific localization or expression.
Full-text availability flags are distinguished from the sections actually read. Detailed access notes are attached to individual reference assessments and the consultation records. Canonical source bytes, citation identifiers and fetched titles are unchanged. No hand-authored publication cache or provider report is created.
Nine short exact anchors are added once each to the revised YAML; the new journal appendix adds no quotation words. Their per-source totals are checked against the immutable caches and prior journal quotations. The inherited 2026-03-19 journal already contains more than 25 quoted words for some sources, including PMID:27516456 and PMID:31454269; those historical quotations are not rewritten or expanded, and no new quote from those sources is added. This explicitly separates inherited content from the present quotation allocation rather than claiming the old journal satisfies a new limit.
All 115 source assertions have now been assessed: 48 ACCEPT, 49 KEEP_AS_NON_CORE, 7 MODIFY and 11 UNDECIDED. The independent 27-row consultation and four-core synthesis check are integrated. Preliminary normal validation passed with 11 advisories: eight supported-binding policy warnings, source-specific differences for vesicle and transporter-binding evidence, and unused provider support. The vesicle distinction reflects an unresolved NCKX4 membrane-versus-vesicle experiment versus independently curated human vesicle proteomics; transporter-binding roles differ between the core RyR2 mechanism and other partners. The seven actually used primary references have since been recovered through the unchanged normal source workflow and imported as exact new caches; the source-closure section below records their scope. A first preliminary run caught an invalid top-level review_status key; this was corrected to the schema status: DRAFT without biological or source changes, and the failed result and exact consulted snapshot are preserved. The independent whole-review peer and canonical application remain pending. No canonical authored file has been changed.
The seven requested caches were produced by one unchanged normal fetch-pmid subprocess (source run 37173617411, return code 0). The authenticated 22,652-byte artifact was recovered from transport run 37174731265, with the complete ranged log, frame metadata, archive digest and all eleven members checked. ROOT independently verified and exclusively imported the seven publication files; all 33 prior CALM3 gene/cache preimages remained unchanged. No citation cache or provider text was authored manually.
PMID:6355894 and PMID:7492944 provide abstract-level rat cerebellum and PC12 nuclear/chromatin/growth-cone evidence. PMID:9353264 supplies independent CaM–PI3K/p85 binding evidence but does not state the organism in its abstract; it does not establish the uninspected original rat donor experiment. PMID:22848456 has a normal full-text cache: actual relevant Methods and all Results paragraphs were read. Young rat hippocampal slices, endogenous pre/postsynaptic CaM immunogold labeling, neurogranin-dependent redistribution and Schaffer-collateral LTP protocols support the retained specialized synaptic contexts. Figures were not inspected, and antibody localization does not distinguish the three identical calmodulin gene products.
PMID:10854758 reports rat calmodulin mRNA/protein expression after amphetamine, and PMID:16503919 identifies rat calmodulin 2 among corticosterone-responsive transcripts. These do not resolve human CALM3-specific response participation, so those UNDECIDED decisions remain. PMID:21855531 supports CaM recognition of group III mGluR C termini but does not settle the exact type-3 receptor assertion; its UNDECIDED decision also remains. Six recovered sources are abstract-only. Seven reference assessments and source-specific support pointers are added without changing any of the 115 source objects, annotation actions, four cores, products or existing 45 reference entries. No new quotations are introduced in this integration.
Final normal validation after seven-cache integration passed with the same eleven disclosed advisories (actual e74a3c). The exact 115-row projection, no-NEW decision set, four cores, retained source/product identities and nine verbatim anchors were checked again before this handoff. Canonical application and whole-science approval remain reserved for ROOT.
This entry supersedes the earlier pending-publication and uncertainty statements where noted. Calcium sensing is now an explicit molecular-function core, supported by PMID:8631777, PMID:27516456 and PMID:31454269. Its existing calcium-detection process is moved from the kinase unit to this sensor unit; target-directed regulator functions remain separate. No annotation row is added.
The IQGAP2 and IQGAP3 interactions are refined to protein domain specific binding because PMID:21299499 maps binding to IQ peptides. Partner-specific calcium/stability differences are retained. This consolidates evidence for an existing term. Other supported generic binding rows remain non-core under the standing campaign instruction, which takes precedence over the validator's stricter default; the remaining advisories are disclosed, not described as compliance with that default.
The official amphetamine-response and corticosterone-response definitions include expression changes. Those donor results are not rejected merely for being expression measurements. The uncertainty concerns human CALM3 regulatory transfer from the rat experiments in PMID:10854758 and PMID:16503919, not whether the observed rat response occurred.
The coauthor-uploaded PMID:22926577 article supplied Methods, adult cohort and calmodulin abundance data. These resolve the previous access gap but do not establish substantia nigra development. That HEP interpretation is overannotated. The abstract-only canonical cache is unchanged; supplements and raw data were not read.
All 115 machine assertions and 52 reference identities are preserved. This proposal changes five annotation reviews and one reference assessment, adds an explicit sensor core, and retains the four target-regulator functions. No NEW annotation or source-cache edit is introduced. Distinct scientific peer and canonical application are pending.