Calmodulin-3 is a small EF-hand calcium sensor that binds target proteins and couples changes in intracellular calcium to enzyme and ion-channel regulation. Human CALM1, CALM2 and CALM3 share the canonical calmodulin protein sequence, while their transcriptional regulation and disease variants are gene-specific. Calcium-dependent conformational changes enable calmodulin to activate CaMKII-family kinases and calcineurin and to modulate nitric-oxide synthases. Channel-associated calmodulin regulates calcium-dependent inactivation of voltage-gated calcium channels and sarcoplasmic-reticulum calcium release through RyR2, linking calcium sensing to cardiac electrical activity and contraction. CALM3 variants can disrupt these regulatory interactions and cause severe arrhythmia. Cytoplasmic, membrane-associated, nuclear and mitotic pools reflect recruitment to different target complexes.
| GO Term | Evidence | Action | Reason |
|---|---|---|---|
| GO:0005737 cytoplasm | IBA GO_REF:0000033 | ACCEPT | Summary: The exact PTN008588804 cytoplasmic IBD agrees with human cellular assays and the curated UniProt localization. Reason: The exact PTN008588804 cytoplasmic IBD agrees with human cellular assays and the curated UniProt localization. Calmodulin acts as a soluble regulator and can be recruited to membrane-associated partners; the broad source compartment is retained without claiming exclusive cytosolic residence. Propagation Review Root cause: NO FAILURE CORE Sources checked: PANTHER:PTN008588804 SUPPORTS TRANSFER Exact node/term IBD read in cached PTHR23048 PAINT table. Full tree and MSA were not independently reconstructed; human target evidence is legitimate descendant grounding. |
| GO:0005509 calcium ion binding | IBA GO_REF:0000033 | ACCEPT | Summary: The cached PAINT export places calcium binding at PTN000549682 and includes experimentally annotated human calmodulins among its descendants. Reason: The cached PAINT export places calcium binding at PTN000549682 and includes experimentally annotated human calmodulins among its descendants. Target-specific calcium-binding measurements and EF-hand structures independently support this central sensing mechanism; the target appearing among donors is legitimate experimental grounding, not circular transfer. Propagation Review Root cause: NO FAILURE CORE Sources checked: PANTHER:PTN000549682 SUPPORTS TRANSFER Exact node/term IBD read in cached PTHR23048 PAINT table. Full tree and MSA were not independently reconstructed; human target evidence is legitimate descendant grounding. |
| GO:0005634 nucleus | IBA GO_REF:0000033 | KEEP AS NON CORE | Summary: The exact PTN008588804 nuclear IBD is present in the cached family export, with rat calmodulin donors. Reason: The exact PTN008588804 nuclear IBD is present in the cached family export, with rat calmodulin donors. Retain the nuclear pool as a context-dependent localization, corroborated by the curated human sperm-nucleus proteomic annotation; the individual mass-spectrometry target record and full phylogenetic tree were not inspected. Propagation Review Root cause: NO FAILURE NON CORE Sources checked: PANTHER:PTN008588804 SUPPORTS TRANSFER Exact node/term IBD read in cached PTHR23048 PAINT table. Full tree and MSA were not independently reconstructed; human target evidence is legitimate descendant grounding. Supporting Evidence: |
| GO:0010880 regulation of release of sequestered calcium ion into cytosol by sarcoplasmic reticulum | IBA GO_REF:0000033 | ACCEPT | Summary: PTN008588809 carries the exact sarcoplasmic-reticulum calcium-release regulation IBD, including human target evidence. Reason: PTN008588809 carries the exact sarcoplasmic-reticulum calcium-release regulation IBD, including human target evidence. Direct calmodulin-dependent regulation of RyR2 and human CALM1 arrhythmia variants support transfer; the mouse R2474S RyR2 experiment is model evidence rather than a CALM1 patient experiment. The clinical variants in PMID:23040497 belong to CALM1, not CALM3. Protein-level transfer is supported by the shared canonical calmodulin sequence and independent CALM3 A103V/E141K functional evidence; gene-specific clinical observations are not reassigned. Propagation Review Root cause: NO FAILURE CORE Sources checked: PANTHER:PTN008588809 SUPPORTS TRANSFER Exact node/term IBD read in cached PTHR23048 PAINT table. Full tree and MSA were not independently reconstructed; human target evidence is legitimate descendant grounding. |
| GO:0005513 detection of calcium ion | IBA GO_REF:0000033 | ACCEPT | Summary: The exact calcium-detection IBD at PTN008588809 is present, with human calmodulins as experimentally grounded descendants. Reason: The exact calcium-detection IBD at PTN008588809 is present, with human calmodulins as experimentally grounded descendants. Calcium binding changes target regulation rather than simply sequestering an ion, supporting the sensing process. Propagation Review Root cause: NO FAILURE CORE Sources checked: PANTHER:PTN008588809 SUPPORTS TRANSFER Exact node/term IBD read in cached PTHR23048 PAINT table. Full tree and MSA were not independently reconstructed; human target evidence is legitimate descendant grounding. |
| GO:0097720 calcineurin-mediated signaling | IBA GO_REF:0000033 | ACCEPT | Summary: The exact PTN008588809 calcineurin-signaling IBD is present. Reason: The exact PTN008588809 calcineurin-signaling IBD is present. Human calmodulin mutagenesis directly couples calcium-dependent conformational opening to calcineurin activation; calmodulin supplies the regulatory activity, while calcineurin performs dephosphorylation. Propagation Review Root cause: NO FAILURE CORE Sources checked: PANTHER:PTN008588809 SUPPORTS TRANSFER Exact node/term IBD read in cached PTHR23048 PAINT table. Full tree and MSA were not independently reconstructed; human target evidence is legitimate descendant grounding. Supporting Evidence: |
| GO:0005813 centrosome | IBA GO_REF:0000033 | KEEP AS NON CORE | Summary: PTN008588806 explicitly carries centrosome localization with human calmodulin source evidence. Reason: PTN008588806 explicitly carries centrosome localization with human calmodulin source evidence. The CP110 study and UniProt support a centrosomal pool and mitotic redistribution, retained as a cell-cycle context rather than the defining location of all calmodulin activity. Propagation Review Root cause: NO FAILURE NON CORE Sources checked: PANTHER:PTN008588806 SUPPORTS TRANSFER Exact node/term IBD read in cached PTHR23048 PAINT table. Full tree and MSA were not independently reconstructed; human target evidence is legitimate descendant grounding. Supporting Evidence: |
| GO:0043209 myelin sheath | IBA GO_REF:0000033 | KEEP AS NON CORE | Summary: The cached PTN008588809 IBD explicitly supports myelin-sheath localization from rodent descendants. Reason: The cached PTN008588809 IBD explicitly supports myelin-sheath localization from rodent descendants. PMID:19855925 independently reports CaM/MBP colocalization in myelin sheaths as well as human-brain MBP association. Retain the conserved specialized pool as non-core; the complete localization Methods/images and gene-specific CALM3 contribution were not inspected or established. Propagation Review Root cause: NO FAILURE NON CORE Sources checked: PANTHER:PTN008588809 SUPPORTS TRANSFER Exact node/term IBD read in cached PTHR23048 PAINT table. Full tree and MSA were not independently reconstructed; human target evidence is legitimate descendant grounding. Supporting Evidence: |
| GO:0000922 spindle pole | IEA GO_REF:0000120 | KEEP AS NON CORE | Summary: The electronic spindle/centrosome localization agrees with the experimentally curated UniProt record, which describes mitotic enrichment at spindle poles and spindle microtubules. Reason: The electronic spindle/centrosome localization agrees with the experimentally curated UniProt record, which describes mitotic enrichment at spindle poles and spindle microtubules. The accessible CP110 cache contains selected narrative rather than the complete localization experiment, so the precise source resolution is retained by curator deference without claiming a newly inspected image. Propagation Review Root cause: NO FAILURE NON CORE Sources checked: ARBA:ARBA00092938 SUPPORTS TRANSFER Literal source identifier preserved. Exact donor/rule experiment access and independent human corroboration are delimited in the reason; no source count or target-self circularity argument is used. UniProtKB-SubCell:SL-0448 SUPPORTS TRANSFER Literal source identifier preserved. Exact donor/rule experiment access and independent human corroboration are delimited in the reason; no source count or target-self circularity argument is used. Supporting Evidence: |
| GO:0002027 regulation of heart rate | IEA GO_REF:0000117 | ACCEPT | Summary: Human CALM1 variants segregate with or arise de novo in severe ventricular arrhythmia, and target-channel studies connect calcium sensing to rhythm control. Reason: Human CALM1 variants segregate with or arise de novo in severe ventricular arrhythmia, and target-channel studies connect calcium sensing to rhythm control. This supports the regulatory role in heart rate; it does not identify CALM1 as the pacemaker ion channel. The clinical variants in PMID:23040497 belong to CALM1, not CALM3. Protein-level transfer is supported by the shared canonical calmodulin sequence and independent CALM3 A103V/E141K functional evidence; gene-specific clinical observations are not reassigned. Propagation Review Root cause: NO FAILURE CORE Sources checked: ARBA:ARBA00087882 SUPPORTS TRANSFER Literal source identifier preserved. Exact donor/rule experiment access and independent human corroboration are delimited in the reason; no source count or target-self circularity argument is used. |
| GO:0005246 calcium channel regulator activity | IEA GO_REF:0000117 | ACCEPT | Summary: Calmodulin directly regulates calcium-channel gating, including calcium-dependent inactivation of CaV1.2 and inhibition of RyR2-mediated calcium release. Reason: Calmodulin directly regulates calcium-channel gating, including calcium-dependent inactivation of CaV1.2 and inhibition of RyR2-mediated calcium release. This target-supported activity justifies the broad electronic regulator assertion; the protein is a regulator rather than a pore-forming channel. Propagation Review Root cause: NO FAILURE CORE Sources checked: ARBA:ARBA00085486 SUPPORTS TRANSFER Literal source identifier preserved. Exact donor/rule experiment access and independent human corroboration are delimited in the reason; no source count or target-self circularity argument is used. |
| GO:0005509 calcium ion binding | IEA GO_REF:0000120 | ACCEPT | Summary: Calmodulin is an EF-hand calcium sensor. Reason: The combined electronic assertion cites rodent calmodulins, an Ensembl product and an EF-hand domain. Direct human calmodulin affinity and conformational measurements independently establish calcium binding; the conclusion does not depend on assuming a rodent expression pattern transfers to CALM3. |
| GO:0005513 detection of calcium ion | IEA GO_REF:0000117 | ACCEPT | Summary: The ARBA calcium-detection assertion agrees with direct coupling between calcium binding, conformational change and target-enzyme activation. Reason: The ARBA calcium-detection assertion agrees with direct coupling between calcium binding, conformational change and target-enzyme activation. This is the calcium-sensor mechanism, not catalytic conversion of calcium. Propagation Review Root cause: NO FAILURE CORE Sources checked: ARBA:ARBA00086881 SUPPORTS TRANSFER Literal source identifier preserved. Exact donor/rule experiment access and independent human corroboration are delimited in the reason; no source count or target-self circularity argument is used. Supporting Evidence: |
| GO:0005813 centrosome | IEA GO_REF:0000120 | KEEP AS NON CORE | Summary: The electronic spindle/centrosome localization agrees with the experimentally curated UniProt record, which describes mitotic enrichment at spindle poles and spindle microtubules. Reason: The electronic spindle/centrosome localization agrees with the experimentally curated UniProt record, which describes mitotic enrichment at spindle poles and spindle microtubules. The accessible CP110 cache contains selected narrative rather than the complete localization experiment, so the precise source resolution is retained by curator deference without claiming a newly inspected image. Propagation Review Root cause: NO FAILURE NON CORE Sources checked: ARBA:ARBA00029136 SUPPORTS TRANSFER Literal source identifier preserved. Exact donor/rule experiment access and independent human corroboration are delimited in the reason; no source count or target-self circularity argument is used. UniProtKB-SubCell:SL-0048 SUPPORTS TRANSFER Literal source identifier preserved. Exact donor/rule experiment access and independent human corroboration are delimited in the reason; no source count or target-self circularity argument is used. Supporting Evidence: |
| GO:0005819 spindle | IEA GO_REF:0000044 | KEEP AS NON CORE | Summary: The electronic spindle/centrosome localization agrees with the experimentally curated UniProt record, which describes mitotic enrichment at spindle poles and spindle microtubules. Reason: The electronic spindle/centrosome localization agrees with the experimentally curated UniProt record, which describes mitotic enrichment at spindle poles and spindle microtubules. The accessible CP110 cache contains selected narrative rather than the complete localization experiment, so the precise source resolution is retained by curator deference without claiming a newly inspected image. Propagation Review Root cause: NO FAILURE NON CORE Sources checked: UniProtKB-SubCell:SL-0251 SUPPORTS TRANSFER Literal source identifier preserved. Exact donor/rule experiment access and independent human corroboration are delimited in the reason; no source count or target-self circularity argument is used. Supporting Evidence: |
| GO:0005876 spindle microtubule | IEA GO_REF:0000117 | KEEP AS NON CORE | Summary: The electronic spindle/centrosome localization agrees with the experimentally curated UniProt record, which describes mitotic enrichment at spindle poles and spindle microtubules. Reason: The electronic spindle/centrosome localization agrees with the experimentally curated UniProt record, which describes mitotic enrichment at spindle poles and spindle microtubules. The accessible CP110 cache contains selected narrative rather than the complete localization experiment, so the precise source resolution is retained by curator deference without claiming a newly inspected image. Propagation Review Root cause: NO FAILURE NON CORE Sources checked: ARBA:ARBA00033575 SUPPORTS TRANSFER Literal source identifier preserved. Exact donor/rule experiment access and independent human corroboration are delimited in the reason; no source count or target-self circularity argument is used. Supporting Evidence: |
| GO:0010856 adenylate cyclase activator activity | IEA GO_REF:0000117 | KEEP AS NON CORE | Summary: Direct structural evidence establishes activation of the anthrax edema-factor adenylate cyclase by human calmodulin. Reason: Direct structural evidence establishes activation of the anthrax edema-factor adenylate cyclase by human calmodulin. Retain that real biochemical activity as a pathogen-associated context; this paper alone does not establish activation of a mammalian GPCR-linked adenylate cyclase. Propagation Review Root cause: NO FAILURE NON CORE Sources checked: ARBA:ARBA00084977 SUPPORTS TRANSFER Literal source identifier preserved. Exact donor/rule experiment access and independent human corroboration are delimited in the reason; no source count or target-self circularity argument is used. Supporting Evidence: |
| GO:0010881 regulation of cardiac muscle contraction by regulation of the release of sequestered calcium ion | IEA GO_REF:0000117 | ACCEPT | Summary: Calmodulin regulates RyR2-dependent sarcoplasmic-reticulum calcium release, linking its own channel-regulatory work to cardiac contraction. Reason: Calmodulin regulates RyR2-dependent sarcoplasmic-reticulum calcium release, linking its own channel-regulatory work to cardiac contraction. The human CALM1 variant study and mouse RyR2 model provide complementary evidence, with their gene and species roles kept distinct. The clinical variants in PMID:23040497 belong to CALM1, not CALM3. Protein-level transfer is supported by the shared canonical calmodulin sequence and independent CALM3 A103V/E141K functional evidence; gene-specific clinical observations are not reassigned. Propagation Review Root cause: NO FAILURE CORE Sources checked: ARBA:ARBA00084948 SUPPORTS TRANSFER Literal source identifier preserved. Exact donor/rule experiment access and independent human corroboration are delimited in the reason; no source count or target-self circularity argument is used. |
| GO:0019901 protein kinase binding | IEA GO_REF:0000117 | MODIFY | Summary: Binding to CaMKII is mechanistically coupled to release of kinase autoinhibition, rather than an unspecified kinase association. Reason: Binding to CaMKII is mechanistically coupled to release of kinase autoinhibition, rather than an unspecified kinase association. Refine the broad electronic binding claim to the independently demonstrated protein serine/threonine kinase activator activity; this does not imply that every kinase bound by calmodulin is activated. Propagation Review Root cause: TERM SCOPING PROBLEM Sources checked: ARBA:ARBA00028598 SUPPORTS TRANSFER Literal source identifier preserved. Exact donor/rule experiment access and independent human corroboration are delimited in the reason; no source count or target-self circularity argument is used. Proposed replacements: protein serine/threonine kinase activator activity |
| GO:0030017 sarcomere | IEA GO_REF:0000117 | ACCEPT | Summary: The curated RyR2 study places calmodulin in a sarcomeric calcium-release context, and independent FRET work reports Z-line-associated RyR2-bound calmodulin. Reason: The curated RyR2 study places calmodulin in a sarcomeric calcium-release context, and independent FRET work reports Z-line-associated RyR2-bound calmodulin. Retain the localization without equating calmodulin with a load-bearing sarcomeric structural protein or claiming that the original image was inspected. Propagation Review Root cause: NO FAILURE CORE Sources checked: ARBA:ARBA00028261 SUPPORTS TRANSFER Literal source identifier preserved. Exact donor/rule experiment access and independent human corroboration are delimited in the reason; no source count or target-self circularity argument is used. |
| GO:0031432 titin binding | IEA GO_REF:0000117 | KEEP AS NON CORE | Summary: The primary human cardiac titin study directly tests recombinant kinase-region constructs and synthetic peptides for calcium-dependent calmodulin binding. Reason: The primary human cardiac titin study directly tests recombinant kinase-region constructs and synthetic peptides for calcium-dependent calmodulin binding. Retain this specific interaction; activation of titin kinase or a mechanosensory role is not established by the inspected abstract. Propagation Review Root cause: NO FAILURE NON CORE Sources checked: ARBA:ARBA00085850 SUPPORTS TRANSFER Literal source identifier preserved. Exact donor/rule experiment access and independent human corroboration are delimited in the reason; no source count or target-self circularity argument is used. Supporting Evidence: |
| GO:0032465 regulation of cytokinesis | IEA GO_REF:0000117 | KEEP AS NON CORE | Summary: Calmodulin binding to CP110 has functional consequences for completion of cytokinesis: a CP110 mutant defective in calmodulin binding induces binucleate cells. Reason: Calmodulin binding to CP110 has functional consequences for completion of cytokinesis: a CP110 mutant defective in calmodulin binding induces binucleate cells. This provides more than an undifferentiated depletion phenotype, but defines a cell-cycle regulatory context rather than a separate universal core activity. Propagation Review Root cause: NO FAILURE NON CORE Sources checked: ARBA:ARBA00084247 SUPPORTS TRANSFER Literal source identifier preserved. Exact donor/rule experiment access and independent human corroboration are delimited in the reason; no source count or target-self circularity argument is used. Supporting Evidence: |
| GO:0034704 calcium channel complex | IEA GO_REF:0000117 | ACCEPT | Summary: Calmodulin is a bound regulatory component of calcium-channel assemblies. Reason: Calmodulin is a bound regulatory component of calcium-channel assemblies. Human RyR2-peptide binding, RyR2-directed FRET and CaV1.2 inactivation experiments support channel-complex association; the source remains a broad complex annotation without an invented channel-specific complex identifier. Propagation Review Root cause: NO FAILURE CORE Sources checked: ARBA:ARBA00085266 SUPPORTS TRANSFER Literal source identifier preserved. Exact donor/rule experiment access and independent human corroboration are delimited in the reason; no source count or target-self circularity argument is used. |
| GO:0043539 protein serine/threonine kinase activator activity | IEA GO_REF:0000117 | ACCEPT | Summary: Human CaMKII/calmodulin structural and binding experiments show how calmodulin releases autoinhibition and permits kinase activation. Reason: Human CaMKII/calmodulin structural and binding experiments show how calmodulin releases autoinhibition and permits kinase activation. The phosphate-transfer activity belongs to CaMKII, while calmodulin is its calcium-responsive activator. Propagation Review Root cause: NO FAILURE CORE Sources checked: ARBA:ARBA00085523 SUPPORTS TRANSFER Literal source identifier preserved. Exact donor/rule experiment access and independent human corroboration are delimited in the reason; no source count or target-self circularity argument is used. |
| GO:0060291 long-term synaptic potentiation | IEA GO_REF:0000117 | KEEP AS NON CORE | Summary: CaMKII activation provides a plausible regulatory contribution to long-term synaptic potentiation, and the cited structural paper discusses that established pathway. Reason: CaMKII activation provides a plausible regulatory contribution to long-term synaptic potentiation, and the cited structural paper discusses that established pathway. Its inspected experiments are purified human kinase/calmodulin structures and binding assays, not a new neuronal potentiation assay; retain the curated pathway assertion as contextual. Propagation Review Root cause: NO FAILURE NON CORE Sources checked: ARBA:ARBA00091239 SUPPORTS TRANSFER Literal source identifier preserved. Exact donor/rule experiment access and independent human corroboration are delimited in the reason; no source count or target-self circularity argument is used. Supporting Evidence: |
| GO:0072542 protein phosphatase activator activity | IEA GO_REF:0000117 | ACCEPT | Summary: Human calmodulin mutants that restrict calcium-induced conformational change lose the ability to activate calcineurin, with activity recovered on chemical reduction. Reason: Human calmodulin mutants that restrict calcium-induced conformational change lose the ability to activate calcineurin, with activity recovered on chemical reduction. This supports the electronic phosphatase-regulatory/calcineurin-signaling assertion without transferring phosphatase catalysis to calmodulin. Propagation Review Root cause: NO FAILURE CORE Sources checked: ARBA:ARBA00090664 SUPPORTS TRANSFER Literal source identifier preserved. Exact donor/rule experiment access and independent human corroboration are delimited in the reason; no source count or target-self circularity argument is used. Supporting Evidence: |
| GO:0097720 calcineurin-mediated signaling | IEA GO_REF:0000117 | ACCEPT | Summary: Human calmodulin mutants that restrict calcium-induced conformational change lose the ability to activate calcineurin, with activity recovered on chemical reduction. Reason: Human calmodulin mutants that restrict calcium-induced conformational change lose the ability to activate calcineurin, with activity recovered on chemical reduction. This supports the electronic phosphatase-regulatory/calcineurin-signaling assertion without transferring phosphatase catalysis to calmodulin. Propagation Review Root cause: NO FAILURE CORE Sources checked: ARBA:ARBA00090525 SUPPORTS TRANSFER Literal source identifier preserved. Exact donor/rule experiment access and independent human corroboration are delimited in the reason; no source count or target-self circularity argument is used. Supporting Evidence: |
| GO:1901844 regulation of cell communication by electrical coupling involved in cardiac conduction | IEA GO_REF:0000117 | ACCEPT | Summary: The human CALM1 arrhythmia study establishes a role in cardiac electrical regulation together with altered calcium sensing and RyR2 interaction. Reason: The human CALM1 arrhythmia study establishes a role in cardiac electrical regulation together with altered calcium sensing and RyR2 interaction. Retain the curated conduction-related regulation; no direct intercellular gap-junction conductance experiment is claimed from the abstract. The clinical variants in PMID:23040497 belong to CALM1, not CALM3. Protein-level transfer is supported by the shared canonical calmodulin sequence and independent CALM3 A103V/E141K functional evidence; gene-specific clinical observations are not reassigned. Propagation Review Root cause: NO FAILURE CORE Sources checked: ARBA:ARBA00091451 SUPPORTS TRANSFER Literal source identifier preserved. Exact donor/rule experiment access and independent human corroboration are delimited in the reason; no source count or target-self circularity argument is used. |
| GO:0005515 protein binding | IPI PMID:35271311 OpenCell: Endogenous tagging for the cartography of human ce... | KEEP AS NON CORE | Summary: Retain the experimentally curated MYO1C association with explicit assay limits. Reason: The exact P0DP25–O00159 MYO1C edge is present in the immutable CALM3 UniProt IntAct section. The complete OpenCell abstract and available Discussion describe endogenous tagging, imaging and proteomic interaction mapping in HEK293T cells. The specific MYO1C table entry and a binary interface were not inspected. Defer to the original IPI curation for this supported association; do not infer myosin motor activity or a CALM3-specific expression mechanism. |
| GO:0000785 chromatin | IEA GO_REF:0000120 | KEEP AS NON CORE | Summary: Chromatin association is supported in rat neuronal preparations. Reason: The cached PMID:6355894 abstract explicitly reports calmodulin immunoreactivity associated with nuclear chromatin by electron microscopy in rat cerebellum. This supports a context-dependent location for the shared calmodulin protein, not a unique human CALM3 gene program. The exact contemporary Ensembl donor chain was not independently reconstructed; the source fields remain unchanged. |
| GO:0001975 response to amphetamine | IEA GO_REF:0000120 | UNDECIDED | Summary: The rat response is established; the human CALM3 transfer remains unresolved. Reason: GO:0001975 explicitly includes stimulus-associated changes in gene expression and enzyme production. Thus the rat calmodulin mRNA/protein changes in PMID:10854758 are relevant response evidence, not automatically invalid because they are expression measurements. Its complete cached abstract describes regional and time-dependent changes after acute/repeated amphetamine and withdrawal. The unresolved issue is transfer to human CALM3: neither the exact gene-specific response nor conservation of its regulation is established by identical protein sequence. Retain UNDECIDED for that transfer, without inferring absence of a human response or proposing a new process annotation. |
| GO:0005634 nucleus | IEA GO_REF:0000120 | KEEP AS NON CORE | Summary: Nuclear calmodulin is supported in a neuronal cell context. Reason: The complete cached PMID:7492944 abstract reports nuclear calmodulin immunostaining in undifferentiated and differentiated rat PC12 cells, corroborated by the rat cerebellar localization in PMID:6355894. The MGI/RGD graph traces the rat nucleus assertion to 7492944. Retain this conserved protein localization as non-core while keeping the rodent and antibody-based context distinct from a CALM3-specific human assay. |
| GO:0008076 voltage-gated potassium channel complex | IEA GO_REF:0000120 | KEEP AS NON CORE | Summary: Calmodulin can be an auxiliary component of KCNQ2/3 channels. Reason: The complete cached PMID:12223552 abstract reports constitutive KCNQ2/3 association, coimmunoprecipitation from mouse brain, binding-site mutants and functional channel tests in CHO cells. This directly supports channel-complex association for the identical calmodulin protein. It neither assigns the potassium pore to calmodulin nor demonstrates an exclusive human CALM3 gene contribution. |
| GO:0016020 membrane | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Membrane-associated calmodulin is supported without membrane-spanning topology. Reason: The mouse donor assertion traces locally to PMID:33199372. Actual Results describe endogenous calmodulin redistribution to transfected NCKX4 sites, dependence on the NCKX4 binding site and coimmunoprecipitation in HEK293 cells. This supports recruited membrane association, while the paper explicitly cannot resolve plasma membrane from immediately adjacent vesicles. Retain the broad location without an integral-membrane or organelle-lumen claim. |
| GO:0019904 protein domain specific binding | IEA GO_REF:0000120 | KEEP AS NON CORE | Summary: Calmodulin recognizes defined target-protein domains. Reason: Independent cached PMID:12223552 reports binding to defined KCNQ2 C-terminal motifs with deletion and point-mutant tests; actual PMID:33199372 Results restrict NCKX4 binding to its cytosolic loop segment. The normal cached PMID:21855531 abstract also describes CaM recognition of group III mGluR C termini, but its full domain-assay details were not inspected. These support protein-domain recognition by the shared protein. Retain the existing broad binding term without guessing a single finer domain shared by every partner. |
| GO:0030235 nitric-oxide synthase regulator activity | IEA GO_REF:0000120 | ACCEPT | Summary: Calmodulin directly regulates nitric-oxide synthase. Reason: The source is a rodent-supported electronic assertion. Independent curated human Reactome evidence describes calmodulin relieving caveolin inhibition of eNOS. This directly supports calmodulin regulator activity, whose official definition is binding and modulation of nitric-oxide synthase; NO synthesis is catalyzed by NOS, not calmodulin. The shared canonical protein supports the biochemical inference, without establishing CALM3-specific endothelial expression or claiming the original rat experiment was read. Supporting Evidence: Reactome:R-HSA-202110 UniProt:P0DP25 |
| GO:0030426 growth cone | IEA GO_REF:0000120 | KEEP AS NON CORE | Summary: Growth-cone localization has direct rat neuronal evidence. Reason: The dated MGI/RGD graph points to PMID:7492944, whose complete normal cached abstract explicitly reports strong calmodulin staining in growth cones of differentiated PC12 neurites. This supports a specialized location for the shared protein. It does not independently establish CALM3-selective expression in human growth cones or a new axon-growth process. |
| GO:0030672 synaptic vesicle membrane | IEA GO_REF:0000120 | UNDECIDED | Summary: The specific synaptic-vesicle membrane assignment remains unresolved. Reason: The dated MGI/RGD graph associates rat calmodulin and this location with the donor publication. Primary identity was recovered, but direct PMC access challenged and the specific calmodulin membrane-localization experiment was not recovered from the publisher. Independent endocytosis physiology establishes calmodulin participation, not by itself a vesicle-membrane location. Preserve this assertion as uncertain rather than declaring the experimental donor wrong. Supporting Evidence: GO_REF:0000120 |
| GO:0031800 type 3 metabotropic glutamate receptor binding | IEA GO_REF:0000120 | UNDECIDED | Summary: The exact type-3 metabotropic glutamate receptor interaction remains unverified. Reason: The dated MGI/RGD graph assigns PMID:21855531 to this rat interaction. Its complete normal cached abstract establishes calmodulin competition with CaBP1 at presynaptic group III mGluRs, but does not identify the exact type-3 receptor assay behind this GO assertion. Group III terminology is not interchangeable with receptor subtype 3. The relevant target panel was not inspected; retain uncertainty without claiming a title-based misattribution. |
| GO:0031966 mitochondrial membrane | IEA GO_REF:0000120 | UNDECIDED | Summary: Mitochondrial-membrane association requires the unresolved donor-specific assay. Reason: The dated MGI/RGD graph traces this rat assertion to the donor publication. The exact calmodulin localization or recruitment experiment could not be read in the accessible primary record. Its Bcl-xL/Drp1 subject does not exclude a calmodulin assay, but neither general synaptic signaling nor necessity for trafficking resolves this particular location. Supporting Evidence: GO_REF:0000120 |
| GO:0031982 vesicle | IEA GO_REF:0000107 | UNDECIDED | Summary: The donor paper does not resolve a vesicular pool in the inspected passages. Reason: Actual PMID:33199372 Results and Discussion support calmodulin interaction with NCKX4 near the cell membrane, but explicitly leave retention on adjacent vesicles versus plasma-membrane localization unresolved. Preserve the mouse IDA-derived assertion and the possibility of an uninspected resolving assay, while avoiding conversion of the authors’ trafficking alternative into a demonstrated vesicle location. |
| GO:0043209 myelin sheath | IEA GO_REF:0000120 | KEEP AS NON CORE | Summary: Myelin-sheath association is directly supported for the shared protein. Reason: The complete cached PMID:19855925 abstract reports calmodulin–MBP colocalization in myelin sheaths and biochemical human-brain/rodent protein work. The exact experimental accession-to-assay mapping is not independently resolved. The already inspected official erratum corrects Figure5a/b reproduction and an axis unit; corrected images were not inspected and no quantitative circular-dichroism result is claimed. |
| GO:0043548 phosphatidylinositol 3-kinase binding | IEA GO_REF:0000120 | KEEP AS NON CORE | Summary: Phosphatidylinositol 3-kinase binding has independent biochemical support. Reason: The original rat donor assay remains uninspected, but the complete cached PMID:9353264 abstract independently reports calcium/calmodulin association with p85 SH2 domains by coimmunoprecipitation and affinity chromatography. Retain the broad binding claim for the shared calmodulin protein; do not transfer lipid-kinase catalysis to calmodulin or claim a uniquely CALM3-derived human assay. |
| GO:0044305 calyx of Held | IEA GO_REF:0000120 | KEEP AS NON CORE | Summary: Calmodulin acts in the calyx of Held synaptic setting. Reason: The complete cached PMID:31628181 abstract describes mouse calmodulin-2 knockout, calyx-type synaptic capacitance measurements and impaired endocytosis. Local mouse GOA contains the corresponding IDA/IMP donor assertions. This supports the shared calmodulin protein acting in that specialized synapse, while the knockout is gene-2-specific and not a direct human CALM3 localization experiment. |
| GO:0044325 transmembrane transporter binding | IEA GO_REF:0000120 | KEEP AS NON CORE | Summary: Transmembrane-transporter binding is an established calmodulin capability. Reason: Independent cached PMID:12223552 establishes KCNQ2/3 binding; actual PMID:33199372 Results establish calcium-dependent NCKX4 binding with purified loop fragments and cellular interaction controls. These support the molecular binding capability of the identical protein regardless of the unresolved exact rat donor paper. Retain the binding annotation without assigning transporter catalysis to calmodulin. |
| GO:0048306 calcium-dependent protein binding | IEA GO_REF:0000120 | ACCEPT | Summary: Calcium-dependent target binding is a fundamental calmodulin function. Reason: Actual PMID:33199372 Results compare NCKX4-fragment binding with and without calcium and use binding-site and calcium-binding-deficient controls. This directly supports calcium-dependent protein binding; not every calmodulin partner must require calcium, since other complexes can bind apo-calmodulin. The conserved protein mechanism is distinct from gene-specific expression. |
| GO:0050998 nitric-oxide synthase binding | IEA GO_REF:0000120 | MODIFY | Summary: Refine NOS binding to the demonstrated NOS-regulatory activity. Reason: The literal rodent donor products and their binding assertion are preserved. Human Reactome describes calmodulin binding as relieving caveolin inhibition of eNOS, providing a functional consequence beyond association. Refine to nitric-oxide synthase regulator activity, which includes NOS binding; do not transfer NOS catalysis to calmodulin. The original rat binding experiment was not independently inspected. Proposed replacements: nitric-oxide synthase regulator activity Supporting Evidence: Reactome:R-HSA-202110 UniProt:P0DP25 |
| GO:0051412 response to corticosterone | IEA GO_REF:0000120 | UNDECIDED | Summary: A valid rat transcriptional response does not resolve the human CALM3 regulatory transfer. Reason: GO:0051412 explicitly includes changes in gene expression following corticosterone exposure. The rat hippocampal-slice transcript and qPCR evidence in PMID:16503919 is therefore relevant to the response term, rather than a reason to reject the donor experiment. The historical mapping identifies rat Calm2; conservation of the encoded protein does not establish conservation of CALM3 promoter responsiveness in humans. The exact human CALM3 inference remains unverified, so retain UNDECIDED for the transfer. This does not claim that CALM3 mediates a particular downstream steroid response or that expression alone proves an unrelated developmental process. |
| GO:0097225 sperm midpiece | IEA GO_REF:0000107 | UNDECIDED | Summary: The calmodulin-specific sperm-midpiece localization assay remains uninspected. Reason: Local mouse GOA traces the location to PMID:29025071. Its complete cached abstract reports FAM71D localization in sperm flagella and its coimmunoprecipitation with calmodulin, with mouse and human material. It does not expose the exact calmodulin-midpiece image or assay. Do not transfer the partner’s localization automatically, and do not reject the curator merely because FAM71D leads the abstract. |
| GO:0098685 Schaffer collateral - CA1 synapse | IEA GO_REF:0000120 | KEEP AS NON CORE | Summary: Rat Schaffer-collateral/CA1 calmodulin localization and signaling support a specialized shared-protein role. Reason: Actual cached PMID:22848456 Methods and Results use rat organotypic hippocampal slices, endogenous calmodulin immunogold labeling in CA1 synapses and Schaffer-collateral stimulation. This independently supports calmodulin in this synaptic setting. Exact human CALM3 gene attribution and the current Ensembl-to-donor snapshot were not established. |
| GO:0099523 presynaptic cytosol | IEA GO_REF:0000120 | KEEP AS NON CORE | Summary: Presynaptic calmodulin has direct rodent synaptic evidence. Reason: Actual cached PMID:22848456 Results explicitly detect endogenous calmodulin immunogold in the presynaptic as well as postsynaptic compartment of rat CA1 synapses. Cached PMID:31628181 and local mouse experimental donor rows independently support presynaptic calcium-sensor function. Retain the specialized location with rodent, shared-protein and antibody-context limits; do not claim isoform-specific human CALM3 imaging. |
| GO:0099524 postsynaptic cytosol | IEA GO_REF:0000120 | KEEP AS NON CORE | Summary: Postsynaptic calmodulin localization is directly observed in rat CA1 dendritic spines. Reason: Actual cached PMID:22848456 Methods and Results report endogenous calmodulin immunogold in postsynaptic compartments and within dendritic spines, with neurogranin changing its distribution. This supports the specialized shared-protein location. Antibody labeling does not discriminate the three identical gene products, and no human CALM3-selective localization experiment is claimed. |
| GO:0140238 presynaptic endocytosis | IEA GO_REF:0000120 | KEEP AS NON CORE | Summary: Calmodulin participates as a calcium sensor in presynaptic endocytosis. Reason: The complete cached PMID:31628181 abstract reports mouse Calm2 knockout effects on slow, rapid and bulk endocytosis and rescue with wild-type but not calcium-binding-deficient calmodulin. This identifies a sensor contribution to the machinery, not merely an unrelated expression correlation. Preserve the mouse gene-2 and shared-protein context without asserting a CALM3-specific human knockout result. |
| GO:0141110 transporter inhibitor activity | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Transporter inhibition is supported in a defined NCKX4 regulatory context. Reason: Actual PMID:33199372 Results show that wild-type calmodulin suppresses ATP-induced NCKX4 stimulation, with calcium-binding-deficient calmodulin and NCKX4-site mutants as controls. The expression construct is chicken CALM2 encoding protein identical to mouse/human calmodulin; NCKX4 is mouse and the cell system HEK293. Basal activity did not show a simple universal decrease. Context dependence does not invalidate a demonstrated inhibitor activity; no claim that all calmodulin targets are inhibited is made. |
| GO:1900242 regulation of synaptic vesicle endocytosis | IEA GO_REF:0000120 | KEEP AS NON CORE | Summary: Regulation of synaptic endocytosis is independently established. Reason: The original rat donor experiment remains uninspected, but cached PMID:31628181 directly supports a calcium-sensor mechanism through mouse Calm2 knockout and calcium-binding-dependent rescue of endocytosis. Retain the regulatory process for the shared protein as non-core; do not claim exact rat donor verification or a human CALM3-specific perturbation. |
| GO:1905913 negative regulation of calcium ion export across plasma membrane | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Calmodulin can restrain NCKX4-mediated calcium extrusion in a defined signaling context. Reason: Actual PMID:33199372 Results and Methods quantify reverse-mode calcium entry as the exchanger-activity assay and show reduced ATP-induced stimulation with calmodulin. The paper interprets this modulation as a brake on physiological NCKX4 calcium extrusion. Retain the donor-derived non-core process with that assay-direction and heterologous mouse-exchanger/chicken-calmodulin boundary; the detailed phosphorylation/reorientation model remains proposed. |
| GO:2000300 regulation of synaptic vesicle exocytosis | IEA GO_REF:0000120 | UNDECIDED | Summary: The exact synaptic-exocytosis regulatory donor experiment remains unresolved. Reason: The dated MGI/RGD graph connects this rat process to the donor publication, but the relevant calmodulin experiment was not recovered. The independent mouse endocytosis study also reports vesicle mobilization effects, yet that does not on its own specify the original exocytosis step. Preserve uncertainty rather than deny calmodulin’s established roles in secretion. Supporting Evidence: GO_REF:0000120 |
| GO:0005829 cytosol | TAS Reactome:R-HSA-9956602 | ACCEPT | Summary: Cytosolic calmodulin participates in the OspC3 regulatory complex. Reason: The complete cached human reaction narrative describes calmodulin association with bacterial OspC3 and stabilization of its CASP4-targeting assembly. This is compatible with the independently curated cytosolic calmodulin pool. OspC3 performs ADP-riboxanation; calmodulin provides binding/regulatory assistance and is not assigned that catalytic activity. The cache is a reaction summary, not an independently inspected compartment graph or full primary paper. Supporting Evidence: Reactome:R-HSA-9956602 UniProt:P0DP25 |
| GO:0005829 cytosol | TAS Reactome:R-HSA-9956624 | ACCEPT | Summary: Cytosolic calmodulin participates in the OspC3 regulatory complex. Reason: The complete cached human reaction narrative describes calmodulin association with bacterial OspC3 and stabilization of its CASP4-targeting assembly. This is compatible with the independently curated cytosolic calmodulin pool. OspC3 performs ADP-riboxanation; calmodulin provides binding/regulatory assistance and is not assigned that catalytic activity. The cache is a reaction summary, not an independently inspected compartment graph or full primary paper. Supporting Evidence: Reactome:R-HSA-9956624 UniProt:P0DP25 |
| GO:0005829 cytosol | TAS Reactome:R-HSA-9956667 | ACCEPT | Summary: Cytosolic calmodulin participates in the OspC3 regulatory complex. Reason: The complete cached human reaction narrative describes calmodulin association with bacterial OspC3 and stabilization of its CASP4-targeting assembly. This is compatible with the independently curated cytosolic calmodulin pool. OspC3 performs ADP-riboxanation; calmodulin provides binding/regulatory assistance and is not assigned that catalytic activity. The cache is a reaction summary, not an independently inspected compartment graph or full primary paper. Supporting Evidence: Reactome:R-HSA-9956667 UniProt:P0DP25 |
| GO:0010881 regulation of cardiac muscle contraction by regulation of the release of sequestered calcium ion | IDA PMID:23040497 Mutations in calmodulin cause ventricular tachycardia and su... | ACCEPT | Summary: The CALM1 variant study combines human arrhythmia genetics with altered calcium binding and RyR2-domain interaction. Reason: The CALM1 variant study combines human arrhythmia genetics with altered calcium binding and RyR2-domain interaction. Retain the curated regulation of cardiac contraction through calcium release, distinguishing protein-level mechanism from a direct contraction experiment not exposed in the cached abstract. The clinical variants in PMID:23040497 belong to CALM1, not CALM3. Protein-level transfer is supported by the shared canonical calmodulin sequence and independent CALM3 A103V/E141K functional evidence; gene-specific clinical observations are not reassigned. |
| GO:1901844 regulation of cell communication by electrical coupling involved in cardiac conduction | IDA PMID:23040497 Mutations in calmodulin cause ventricular tachycardia and su... | ACCEPT | Summary: Human CALM1 substitutions are associated with ventricular arrhythmia and disturbed calcium-sensor/channel coupling. Reason: Human CALM1 substitutions are associated with ventricular arrhythmia and disturbed calcium-sensor/channel coupling. Retain the curated electrical-coupling regulatory process with that evidence boundary; the abstract does not independently demonstrate a gap-junction mechanism. The clinical variants in PMID:23040497 belong to CALM1, not CALM3. Protein-level transfer is supported by the shared canonical calmodulin sequence and independent CALM3 A103V/E141K functional evidence; gene-specific clinical observations are not reassigned. |
| GO:0005246 calcium channel regulator activity | IDA PMID:20226167 Defective calmodulin binding to the cardiac ryanodine recept... | ACCEPT | Summary: In a mouse RyR2-R2474S model, altered calmodulin affinity accompanies abnormal calcium release, and added calmodulin attenuates calcium sparks. Reason: In a mouse RyR2-R2474S model, altered calmodulin affinity accompanies abnormal calcium release, and added calmodulin attenuates calcium sparks. This supports calmodulin channel regulation and its calcium-release/contraction consequences; the mutated molecule in that experiment is RyR2, not a CALM3 patient allele. Supporting Evidence: |
| GO:0010881 regulation of cardiac muscle contraction by regulation of the release of sequestered calcium ion | IDA PMID:20226167 Defective calmodulin binding to the cardiac ryanodine recept... | ACCEPT | Summary: In a mouse RyR2-R2474S model, altered calmodulin affinity accompanies abnormal calcium release, and added calmodulin attenuates calcium sparks. Reason: In a mouse RyR2-R2474S model, altered calmodulin affinity accompanies abnormal calcium release, and added calmodulin attenuates calcium sparks. This supports calmodulin channel regulation and its calcium-release/contraction consequences; the mutated molecule in that experiment is RyR2, not a CALM3 patient allele. Supporting Evidence: |
| GO:0060291 long-term synaptic potentiation | TAS PMID:20668654 Structure of the CaMKIIdelta/calmodulin complex reveals the ... | KEEP AS NON CORE | Summary: CaMKII activation provides a plausible regulatory contribution to long-term synaptic potentiation, and the cited structural paper discusses that established pathway. Reason: CaMKII activation provides a plausible regulatory contribution to long-term synaptic potentiation, and the cited structural paper discusses that established pathway. Its inspected experiments are purified human kinase/calmodulin structures and binding assays, not a new neuronal potentiation assay; retain the curated pathway assertion as contextual. Supporting Evidence: |
| GO:0097720 calcineurin-mediated signaling | IDA PMID:8631777 Blocking the Ca2+-induced conformational transitions in calm... | ACCEPT | Summary: The experiment uses engineered human liver calmodulin with intramolecular disulfides that restrict calcium-induced opening. Reason: The experiment uses engineered human liver calmodulin with intramolecular disulfides that restrict calcium-induced opening. Loss and chemical restoration of calcineurin activation directly support calmodulin phosphatase-activator function and its participation in calcineurin signaling, not phosphatase catalysis. Supporting Evidence: |
| GO:0005515 protein binding | IPI PMID:11984006 The Chediak-Higashi protein interacts with SNARE complex and... | UNDECIDED | Summary: The source supports an interaction-screen framework, but the calmodulin-LYST target evidence remains unresolved. Reason: The complete PMID:11984006 abstract describes human LYST-fragment yeast two-hybrid screening and follow-up of selected partners, but does not identify the calmodulin target experiment. The accessible publisher preview did not supply that result and the primary full-text attempt failed. Preserve the original experimental assertion without declaring it wrong; the target-specific evidence and any more specific activity remain unresolved. Supporting Evidence: |
| GO:0005515 protein binding | IPI PMID:19855925 Structural analysis of the complex between calmodulin and fu... | KEEP AS NON CORE | Summary: Retain the myelin-basic-protein interaction in its biochemical context. Reason: The complete PMID:19855925 abstract describes calmodulin-affinity capture of human brain myelin basic protein and structural/biophysical binding experiments with full-length protein and rodent peptides. Retain the exact curated partner P02687; the individual accession-to-assay mapping and full Methods were not independently inspected. The official 2010 correction replaces Figure 5 panels and corrects the circular-dichroism axis unit; its prose was read, but corrected images were not reanalysed. This supports bounded binding without a separate enzyme-regulatory claim. Supporting Evidence: |
| GO:0005509 calcium ion binding | IDA PMID:35568036 A family of conserved bacterial virulence factors dampens in... | ACCEPT | Summary: The OspC study distinguishes apo-calmodulin binding in EDTA from calcium-containing conditions and calcium-dependent downstream signaling. Reason: The OspC study distinguishes apo-calmodulin binding in EDTA from calcium-containing conditions and calcium-dependent downstream signaling. The intrinsic calcium-binding activity is independently established by direct human protein measurements; this retained IDA row is not relabeled as pathway-database evidence. |
| GO:0043539 protein serine/threonine kinase activator activity | IDA PMID:35568036 A family of conserved bacterial virulence factors dampens in... | ACCEPT | Summary: The OspC study measures reduced CaMKII phosphorylation and calmodulin association after bacterial-effector expression, and constitutively active CaMKII bypasses the IFN inhibition. Reason: The OspC study measures reduced CaMKII phosphorylation and calmodulin association after bacterial-effector expression, and constitutively active CaMKII bypasses the IFN inhibition. This supports the calmodulin-activator mechanism in human cell systems, independently established by human CaMKII/calmodulin structural work; the paper is not Reactome evidence. |
| GO:0005509 calcium ion binding | IDA PMID:31454269 Genetic Mosaicism in Calmodulinopathy. | ACCEPT | Summary: The study directly measures impaired C-domain calcium affinity of recombinant E141V and E141K calmodulin proteins. Reason: The study directly measures impaired C-domain calcium affinity of recombinant E141V and E141K calmodulin proteins. CALM1-E141V and CALM3-E141K are distinct genetic observations despite their shared wild-type protein sequence; the two mosaic pedigrees in this paper involve CALM3. Supporting Evidence: |
| GO:0098901 regulation of cardiac muscle cell action potential | IMP PMID:31454269 Genetic Mosaicism in Calmodulinopathy. | ACCEPT | Summary: Human iPSC-derived cardiomyocytes overexpressing wild-type or E141 mutant calmodulin show altered L-type-channel calcium-dependent inactivation and action-potential duration. Reason: Human iPSC-derived cardiomyocytes overexpressing wild-type or E141 mutant calmodulin show altered L-type-channel calcium-dependent inactivation and action-potential duration. CALM3-E141K is distinct from CALM1-E141V; the two mosaic pedigrees involve CALM3, including D130G. These experiments support regulation by the shared protein and a direct CALM3 disease context, without claiming detailed supplemental Methods were available. Supporting Evidence: |
| GO:1901842 negative regulation of high voltage-gated calcium channel activity | IMP PMID:31454269 Genetic Mosaicism in Calmodulinopathy. | ACCEPT | Summary: Human iPSC-derived cardiomyocytes overexpressing wild-type or E141 mutant calmodulin show altered L-type-channel calcium-dependent inactivation and action-potential duration. Reason: Human iPSC-derived cardiomyocytes overexpressing wild-type or E141 mutant calmodulin show altered L-type-channel calcium-dependent inactivation and action-potential duration. CALM3-E141K is distinct from CALM1-E141V; the two mosaic pedigrees involve CALM3, including D130G. These experiments support regulation by the shared protein and a direct CALM3 disease context, without claiming detailed supplemental Methods were available. Supporting Evidence: |
| GO:0010856 adenylate cyclase activator activity | IDA PMID:11807546 Structural basis for the activation of anthrax adenylyl cycl... | KEEP AS NON CORE | Summary: The primary structure demonstrates activation of the anthrax edema-factor adenylate cyclase by calmodulin. Reason: The primary structure demonstrates activation of the anthrax edema-factor adenylate cyclase by calmodulin. This is genuine calmodulin activator activity in a microbial-toxin context, not proof of mammalian GPCR-linked cyclase activation. Supporting Evidence: |
| GO:0034704 calcium channel complex | IDA PMID:23040497 Mutations in calmodulin cause ventricular tachycardia and su... | ACCEPT | Summary: The paper reports calmodulin interaction with a RyR2 calmodulin-binding-domain peptide and altered binding of a CALM1 variant. Reason: The paper reports calmodulin interaction with a RyR2 calmodulin-binding-domain peptide and altered binding of a CALM1 variant. Independent RyR2-directed FRET corroborates association with the channel assembly; the isolated peptide experiment is not described as a resolved intact complex. The clinical variants in PMID:23040497 belong to CALM1, not CALM3. Protein-level transfer is supported by the shared canonical calmodulin sequence and independent CALM3 A103V/E141K functional evidence; gene-specific clinical observations are not reassigned. |
| GO:0000922 spindle pole | IDA PMID:16760425 CP110 cooperates with two calcium-binding proteins to regula... | KEEP AS NON CORE | Summary: The curated IDA localization is consistent with UniProt mitotic spindle-pole and spindle-microtubule redistribution, and with the CP110/calmodulin association study. Reason: The curated IDA localization is consistent with UniProt mitotic spindle-pole and spindle-microtubule redistribution, and with the CP110/calmodulin association study. The complete localization figure is absent from the selected cached narrative, so retain the trusted source resolution without claiming a newly inspected image. Supporting Evidence: |
| GO:0005515 protein binding | IPI PMID:10692436 Ca(2+)-dependent and Ca(2+)-independent calmodulin binding s... | MODIFY | Summary: Binding to erythrocyte protein 4.1R supports cytoskeletal protein binding. Reason: The complete PMID:10692436 abstract reports calmodulin binding to protein 4.1R, mapping two binding sites by peptide/deletion analysis and measuring their effects on association with band 3. Protein 4.1R is the membrane-cytoskeletal partner. This supports cytoskeletal protein binding without transferring the partner structural activity to calmodulin; full Methods were unavailable. Proposed replacements: cytoskeletal protein binding Supporting Evidence: PMID:10692436 CaM bound to 4.1R at a stoichiometry of 1:1 |
| GO:0005515 protein binding | IPI PMID:15140941 Ca2+-binding protein-1 facilitates and forms a postsynaptic ... | MODIFY | Summary: Direct CaV1.2 association supports transmembrane transporter binding. Reason: The complete PMID:15140941 abstract and accessible Methods/Discussion support competitive calmodulin association with the channel C terminus and calmodulin-dependent inactivation. The Methods use rat rbcII channel constructs in HEK293T cells and commercial calmodulin; the cache omits the central Results despite its full-text flag. Refine the interaction to transporter binding while retaining the source partner Q13936. Channel inhibition is relevant biological context, but the pore activity belongs to the channel and the source is not a CALM3-specific human physiological assay. Proposed replacements: transmembrane transporter binding Supporting Evidence: |
| GO:0005515 protein binding | IPI PMID:15632291 Myristoyl moiety of HIV Nef is involved in regulation of the... | KEEP AS NON CORE | Summary: Retain the direct HIV-1 Nef interaction. Reason: The complete PMID:15632291 abstract explicitly reports cellular co-immunoprecipitation, recombinant GST-Nef pull-down and binding of Nef peptides to calmodulin, with myristoylation affecting binding. The actual cached body supplies Introduction/Discussion rather than complete Methods/Results. Retain this viral-partner interaction as non-core without inferring a separate calmodulin catalytic activity. Supporting Evidence: |
| GO:0005515 protein binding | IPI PMID:16760425 CP110 cooperates with two calcium-binding proteins to regula... | KEEP AS NON CORE | Summary: Retain the direct CP110 interaction within a centrosomal protein assembly. Reason: PMID:16760425 abstract and accessible Discussion distinguish direct calmodulin-CP110 association from an indirect centrin interaction. Binding-defective CP110 mutants inform the functional context, but do not independently establish a more specific adaptor or catalytic activity of calmodulin. Retain the exact O43303 edge; selected Discussion was read, not all primary assay figures. Supporting Evidence: |
| GO:0005515 protein binding | IPI PMID:21299499 IQ-motif selectivity in human IQGAP2 and IQGAP3: binding of ... | MODIFY | Summary: Refine the IQGAP2 interaction to binding its defined IQ region. Reason: PMID:21299499 uses recombinant human calmodulin and synthetic IQGAP2 IQ peptides to map the interaction to a defined protein region. IQ motifs 2 and 3 interact in calcium, with transient or intermediate stability; motif 1 shows a transient calcium-independent interaction. GO:0019904 captures this mapped domain recognition more precisely than bare protein binding. The original partner is preserved. The refinement consolidates evidence for an already present term and does not establish intact-complex affinity, a universal calcium requirement, GTPase activity or a new cellular process. Proposed replacements: protein domain specific binding Supporting Evidence: |
| GO:0005515 protein binding | IPI PMID:3111527 Comparison of S100b protein with calmodulin: interactions wi... | UNDECIDED | Summary: The original calmodulin-tau assay remains unresolved in the available source. Reason: The canonical PMID:3111527 abstract is explicitly truncated and primarily describes S100b/melittin interactions. The target calmodulin-tau experiment was not recovered from the publisher. Preserve the curator experimental assertion without a wrong-protein claim; the available source does not support a confident refinement or removal. An independently indexed later tau-calmodulin paper was only an uncached lead and is not used as YAML support. Supporting Evidence: |
| GO:0005634 nucleus | HDA PMID:21630459 Proteomic characterization of the human sperm nucleus. | KEEP AS NON CORE | Summary: The primary abstract describes proteomics of purified human sperm nuclei, matching the curated nuclear association. Reason: The primary abstract describes proteomics of purified human sperm nuclei, matching the curated nuclear association. The individual calmodulin peptide assignment was not inspected, and shared calmodulin peptides do not establish CALM3-specific nuclear expression. Supporting Evidence: |
| GO:0005737 cytoplasm | TAS PMID:10899953 Calmodulin regulation of basal and agonist-stimulated G prot... | ACCEPT | Summary: The human mu-opioid-receptor study describes direct calmodulin interaction with the receptor intracellular loop and movement from the plasma membrane on receptor activation in HEK293 cells. Reason: The human mu-opioid-receptor study describes direct calmodulin interaction with the receptor intracellular loop and movement from the plasma membrane on receptor activation in HEK293 cells. Retain the cytoplasmic and peripheral plasma-membrane pools, without assigning membrane-spanning topology. Supporting Evidence: |
| GO:0005813 centrosome | IDA PMID:16760425 CP110 cooperates with two calcium-binding proteins to regula... | KEEP AS NON CORE | Summary: The curated IDA localization is consistent with UniProt mitotic spindle-pole and spindle-microtubule redistribution, and with the CP110/calmodulin association study. Reason: The curated IDA localization is consistent with UniProt mitotic spindle-pole and spindle-microtubule redistribution, and with the CP110/calmodulin association study. The complete localization figure is absent from the selected cached narrative, so retain the trusted source resolution without claiming a newly inspected image. Supporting Evidence: |
| GO:0005876 spindle microtubule | IDA PMID:16760425 CP110 cooperates with two calcium-binding proteins to regula... | KEEP AS NON CORE | Summary: The curated IDA localization is consistent with UniProt mitotic spindle-pole and spindle-microtubule redistribution, and with the CP110/calmodulin association study. Reason: The curated IDA localization is consistent with UniProt mitotic spindle-pole and spindle-microtubule redistribution, and with the CP110/calmodulin association study. The complete localization figure is absent from the selected cached narrative, so retain the trusted source resolution without claiming a newly inspected image. Supporting Evidence: |
| GO:0005886 plasma membrane | TAS PMID:10899953 Calmodulin regulation of basal and agonist-stimulated G prot... | ACCEPT | Summary: The human mu-opioid-receptor study describes direct calmodulin interaction with the receptor intracellular loop and movement from the plasma membrane on receptor activation in HEK293 cells. Reason: The human mu-opioid-receptor study describes direct calmodulin interaction with the receptor intracellular loop and movement from the plasma membrane on receptor activation in HEK293 cells. Retain the cytoplasmic and peripheral plasma-membrane pools, without assigning membrane-spanning topology. Supporting Evidence: PMID:10899953 CaM release from plasma membranes |
| GO:0007186 G protein-coupled receptor signaling pathway | TAS PMID:10899953 Calmodulin regulation of basal and agonist-stimulated G prot... | KEEP AS NON CORE | Summary: The human mu-opioid-receptor experiments identify calmodulin as a direct receptor-associated regulator of basal G-protein coupling. Reason: The human mu-opioid-receptor experiments identify calmodulin as a direct receptor-associated regulator of basal G-protein coupling. Retain this GPCR signaling context separately from activation of bacterial edema-factor adenylate cyclase; the latter is not evidence for this process. Supporting Evidence: |
| GO:0021762 substantia nigra development | HEP PMID:22926577 Quantitative proteomic analysis of human substantia nigra in... | MARK AS OVER ANNOTATED | Summary: Adult disease-associated protein abundance does not establish substantia nigra development. Reason: The coauthor-uploaded PMID:22926577 article was checked beyond its abstract: Methods and Table 1 describe adult postmortem samples; Table 2 and the Alzheimer disease Results identify calmodulin abundance. These measurements do not test formation or maturation of the substantia nigra, which GO:0021762 denotes. Mark the developmental interpretation as overannotated while retaining the source record and legitimate protein-detection result. This is an assay-scope judgment, not a wrong-gene allegation or a rejection from the title alone. Supporting Evidence: |
| GO:0031982 vesicle | HDA PMID:19190083 Characterization of exosome-like vesicles released from huma... | KEEP AS NON CORE | Summary: The study reports proteomic analysis of exosome-like vesicles from human airway epithelia, consistent with the curated vesicle association. Reason: The study reports proteomic analysis of exosome-like vesicles from human airway epithelia, consistent with the curated vesicle association. The individual calmodulin entry and vesicle-loading mechanism were not inspected; no active secretion or dedicated extracellular function is inferred. Supporting Evidence: |
| GO:0032465 regulation of cytokinesis | IMP PMID:16760425 CP110 cooperates with two calcium-binding proteins to regula... | KEEP AS NON CORE | Summary: The CP110 study combines direct calmodulin binding with a binding-defective CP110 mutant that disrupts late cytokinesis. Reason: The CP110 study combines direct calmodulin binding with a binding-defective CP110 mutant that disrupts late cytokinesis. This supports a functional regulatory contribution beyond mere depletion, while the precise downstream machinery remains unresolved and the role is contextual. Supporting Evidence: |
| GO:0005509 calcium ion binding | IDA PMID:11807546 Structural basis for the activation of anthrax adenylyl cycl... | ACCEPT | Summary: The calmodulin/edema-factor structure provides direct calcium-bound calmodulin evidence. Reason: The calmodulin/edema-factor structure provides direct calcium-bound calmodulin evidence. Calcium binding belongs to calmodulin, whereas adenylate cyclase catalysis belongs to the bacterial partner. Supporting Evidence: |
| GO:0008179 adenylate cyclase binding | IPI PMID:11807546 Structural basis for the activation of anthrax adenylyl cycl... | MODIFY | Summary: Calmodulin binding activates the anthrax edema-factor cyclase. Reason: The source resolves direct association of calmodulin with the bacterial adenylate cyclase edema factor and its activation. Refine cyclase binding to adenylate cyclase activator activity while retaining the exact P40136 partner and pathogen context. The enzyme, not calmodulin, converts ATP to cAMP; this evidence alone does not demonstrate activation of a mammalian GPCR-linked cyclase. Proposed replacements: adenylate cyclase activator activity Supporting Evidence: PMID:11807546 stabilizes a disordered loop and leads to enzyme activation |
| GO:0032991 protein-containing complex | IDA PMID:19855925 Structural analysis of the complex between calmodulin and fu... | KEEP AS NON CORE | Summary: The source directly studies complexes between calmodulin and myelin-basic-protein constructs. Reason: The source directly studies complexes between calmodulin and myelin-basic-protein constructs. Retain the broad complex association without treating every transient complex as a distinct core function or inventing a more specific complex identifier. Supporting Evidence: |
| GO:1902494 catalytic complex | IDA PMID:11807546 Structural basis for the activation of anthrax adenylyl cycl... | KEEP AS NON CORE | Summary: The edema-factor/calmodulin structure places calmodulin in a catalytic assembly as the regulatory partner. Reason: The edema-factor/calmodulin structure places calmodulin in a catalytic assembly as the regulatory partner. Retain this microbial-toxin complex context; it does not make calmodulin catalytic or establish a mammalian GPCR pathway. Supporting Evidence: |
| GO:0002027 regulation of heart rate | IMP PMID:23040497 Mutations in calmodulin cause ventricular tachycardia and su... | ACCEPT | Summary: The CALM1 study identifies segregating and de novo variants with compromised calcium binding and altered RyR2-domain interaction in an arrhythmia context. Reason: The CALM1 study identifies segregating and de novo variants with compromised calcium binding and altered RyR2-domain interaction in an arrhythmia context. This directly links calmodulin sensing to heart-rhythm regulation; its N53I/N97S nomenclature omits the initiator methionine, corresponding to UniProt N54I/N98S. The clinical variants in PMID:23040497 belong to CALM1, not CALM3. Protein-level transfer is supported by the shared canonical calmodulin sequence and independent CALM3 A103V/E141K functional evidence; gene-specific clinical observations are not reassigned. |
| GO:0005509 calcium ion binding | IDA PMID:23040497 Mutations in calmodulin cause ventricular tachycardia and su... | ACCEPT | Summary: The primary CALM1 study directly measures compromised calcium binding of disease-associated calmodulin variants. Reason: The primary CALM1 study directly measures compromised calcium binding of disease-associated calmodulin variants. The mutant names use mature-protein numbering, one residue lower than the UniProt precursor convention. The clinical variants in PMID:23040497 belong to CALM1, not CALM3. Protein-level transfer is supported by the shared canonical calmodulin sequence and independent CALM3 A103V/E141K functional evidence; gene-specific clinical observations are not reassigned. Supporting Evidence: PMID:23040497 Both CALM1 substitutions demonstrated compromised calcium binding |
| GO:0005509 calcium ion binding | IDA PMID:7607248 A calmodulin-binding sequence in the C-terminus of human car... | ACCEPT | Summary: The human cardiac titin study observes calcium-dependent calmodulin/kinase-region complex formation and conformational changes. Reason: The human cardiac titin study observes calcium-dependent calmodulin/kinase-region complex formation and conformational changes. The intrinsic calcium-binding activity is additionally supported by direct calmodulin-affinity experiments, without assigning titin catalytic activity to calmodulin. |
| GO:0005509 calcium ion binding | IDA PMID:8631777 Blocking the Ca2+-induced conformational transitions in calm... | ACCEPT | Summary: Engineered human calmodulin disulfide mutants have decreased calcium affinity and lose target-enzyme activation, with regulatory activity restored after reduction. Reason: Engineered human calmodulin disulfide mutants have decreased calcium affinity and lose target-enzyme activation, with regulatory activity restored after reduction. This directly links EF-hand-dependent calcium binding and conformational regulation. Supporting Evidence: |
| GO:0005513 detection of calcium ion | IMP PMID:23040497 Mutations in calmodulin cause ventricular tachycardia and su... | ACCEPT | Summary: The CALM1 study identifies segregating and de novo variants with compromised calcium binding and altered RyR2-domain interaction in an arrhythmia context. Reason: The CALM1 study identifies segregating and de novo variants with compromised calcium binding and altered RyR2-domain interaction in an arrhythmia context. This directly links calmodulin sensing to heart-rhythm regulation; its N53I/N97S nomenclature omits the initiator methionine, corresponding to UniProt N54I/N98S. The clinical variants in PMID:23040497 belong to CALM1, not CALM3. Protein-level transfer is supported by the shared canonical calmodulin sequence and independent CALM3 A103V/E141K functional evidence; gene-specific clinical observations are not reassigned. |
| GO:0010880 regulation of release of sequestered calcium ion into cytosol by sarcoplasmic reticulum | IDA PMID:20226167 Defective calmodulin binding to the cardiac ryanodine recept... | ACCEPT | Summary: In a mouse RyR2-R2474S model, altered calmodulin affinity accompanies abnormal calcium release, and added calmodulin attenuates calcium sparks. Reason: In a mouse RyR2-R2474S model, altered calmodulin affinity accompanies abnormal calcium release, and added calmodulin attenuates calcium sparks. This supports calmodulin channel regulation and its calcium-release/contraction consequences; the mutated molecule in that experiment is RyR2, not a CALM3 patient allele. Supporting Evidence: |
| GO:0019901 protein kinase binding | IPI PMID:20668654 Structure of the CaMKIIdelta/calmodulin complex reveals the ... | MODIFY | Summary: The source measures direct binding of human calmodulin to the exact CaMKII isozyme and explains release of kinase autoinhibition. Reason: The source measures direct binding of human calmodulin to the exact CaMKII isozyme and explains release of kinase autoinhibition. Refine the unspecified kinase-binding row to the demonstrated serine/threonine kinase activator activity, preserving the original alpha/delta partner and its experimental evidence. Proposed replacements: protein serine/threonine kinase activator activity Supporting Evidence: |
| GO:0030017 sarcomere | IDA PMID:20226167 Defective calmodulin binding to the cardiac ryanodine recept... | ACCEPT | Summary: Retain the curated sarcomeric localization in the RyR2 model. Reason: Retain the curated sarcomeric localization in the RyR2 model. The original localization experiment is not exposed in the cached abstract, but independent FRET experiments place RyR2-associated calmodulin at Z-lines; this does not make calmodulin a sarcomeric structural component. |
| GO:0031432 titin binding | IPI PMID:7607248 A calmodulin-binding sequence in the C-terminus of human car... | KEEP AS NON CORE | Summary: The source directly tests human titin kinase-region constructs and synthetic peptides for equimolar calcium-dependent binding to calmodulin. Reason: The source directly tests human titin kinase-region constructs and synthetic peptides for equimolar calcium-dependent binding to calmodulin. Retain the exact titin partner; the inspected evidence proposes, rather than establishes, a kinase-regulatory consequence. Supporting Evidence: PMID:7607248 Helicity increases upon binding of calmodulin in a calcium-dependent fashion |
| GO:0043539 protein serine/threonine kinase activator activity | TAS PMID:20668654 Structure of the CaMKIIdelta/calmodulin complex reveals the ... | ACCEPT | Summary: The human CaMKII/calmodulin structure and solution-binding experiments explain how calmodulin displaces the inhibitory segment and enables the active kinase configuration. Reason: The human CaMKII/calmodulin structure and solution-binding experiments explain how calmodulin displaces the inhibitory segment and enables the active kinase configuration. This is calmodulin activator activity, while ATP binding and phosphoryl transfer remain activities of CaMKII. Supporting Evidence: |
| GO:0044325 transmembrane transporter binding | IPI PMID:21167176 Solution NMR structure of Apo-calmodulin in complex with the... | KEEP AS NON CORE | Summary: NMR and solution experiments directly demonstrate apo-calmodulin binding to the human NaV1.5 IQ motif. Reason: NMR and solution experiments directly demonstrate apo-calmodulin binding to the human NaV1.5 IQ motif. Retain the specific transmembrane-transporter interaction; the peptide structure alone does not establish every proposed effect on intact-channel gating. Supporting Evidence: PMID:21167176 the Na(V)1.5 IQ motif interacts with the C-terminal domain (C-lobe) of CaM |
| GO:0044325 transmembrane transporter binding | IPI PMID:23040497 Mutations in calmodulin cause ventricular tachycardia and su... | ACCEPT | Summary: The CALM1 variant paper directly measures interaction with the RyR2 calmodulin-binding-domain peptide. Reason: The CALM1 variant paper directly measures interaction with the RyR2 calmodulin-binding-domain peptide. Retain the exact RyR2 partner and transporter-binding subactivity as part of the channel-regulatory mechanism, without claiming that a peptide assay alone resolves the intact complex. The clinical variants in PMID:23040497 belong to CALM1, not CALM3. Protein-level transfer is supported by the shared canonical calmodulin sequence and independent CALM3 A103V/E141K functional evidence; gene-specific clinical observations are not reassigned. |
| GO:0051592 response to calcium ion | IDA PMID:7607248 A calmodulin-binding sequence in the C-terminus of human car... | ACCEPT | Summary: Calcium addition changes calmodulin binding and conformation in the human titin-fragment experiments. Reason: Calcium addition changes calmodulin binding and conformation in the human titin-fragment experiments. This is a genuine calcium response by the sensor protein, incorporated into its target-regulatory mechanism without transferring titin enzyme activity. Supporting Evidence: |
| GO:0055117 regulation of cardiac muscle contraction | IMP PMID:23040497 Mutations in calmodulin cause ventricular tachycardia and su... | ACCEPT | Summary: The human CALM1 variant study supports regulation of cardiac function through calcium sensing and RyR2 coupling. Reason: The human CALM1 variant study supports regulation of cardiac function through calcium sensing and RyR2 coupling. Retain the broader cardiac-contraction regulatory assertion alongside its existing more mechanistic calcium-release child, without adding a redundant new annotation. The clinical variants in PMID:23040497 belong to CALM1, not CALM3. Protein-level transfer is supported by the shared canonical calmodulin sequence and independent CALM3 A103V/E141K functional evidence; gene-specific clinical observations are not reassigned. |
| GO:0072542 protein phosphatase activator activity | IDA PMID:8631777 Blocking the Ca2+-induced conformational transitions in calm... | ACCEPT | Summary: The experiment uses engineered human liver calmodulin with intramolecular disulfides that restrict calcium-induced opening. Reason: The experiment uses engineered human liver calmodulin with intramolecular disulfides that restrict calcium-induced opening. Loss and chemical restoration of calcineurin activation directly support calmodulin phosphatase-activator function and its participation in calcineurin signaling, not phosphatase catalysis. Supporting Evidence: |
| GO:0005509 calcium ion binding | IDA PMID:27516456 Novel CPVT-Associated Calmodulin Mutation in CALM3 (CALM3-A1... | ACCEPT | Summary: The CALM3 A103V study directly supports calcium-dependent channel regulation. Reason: The paper identifies the clinical CALM3-A103V variant and tests recombinant mutant calmodulin, calcium binding, RyR2 regulation and spontaneous calcium-release behavior. Its comparisons with CALM1 N54I/N98S do not change which gene carries A103V. Retain the intrinsic calcium-binding assertion, keeping the human genetic observation separate from the experimental channel and cardiomyocyte systems. Supporting Evidence: |
| GO:0005515 protein binding | IPI PMID:19855925 Structural analysis of the complex between calmodulin and fu... | KEEP AS NON CORE | Summary: Retain the myelin-basic-protein interaction in its biochemical context. Reason: The complete PMID:19855925 abstract describes calmodulin-affinity capture of human brain myelin basic protein and structural/biophysical binding experiments with full-length protein and rodent peptides. Retain the exact curated partner P04370; the individual accession-to-assay mapping and full Methods were not independently inspected. The official 2010 correction replaces Figure 5 panels and corrects the circular-dichroism axis unit; its prose was read, but corrected images were not reanalysed. This supports bounded binding without a separate enzyme-regulatory claim. Supporting Evidence: |
| GO:0005515 protein binding | IPI PMID:19855925 Structural analysis of the complex between calmodulin and fu... | KEEP AS NON CORE | Summary: Retain the myelin-basic-protein interaction in its biochemical context. Reason: The complete PMID:19855925 abstract describes calmodulin-affinity capture of human brain myelin basic protein and structural/biophysical binding experiments with full-length protein and rodent peptides. Retain the exact curated partner P81558; the individual accession-to-assay mapping and full Methods were not independently inspected. The official 2010 correction replaces Figure 5 panels and corrects the circular-dichroism axis unit; its prose was read, but corrected images were not reanalysed. This supports bounded binding without a separate enzyme-regulatory claim. Supporting Evidence: |
| GO:0005515 protein binding | IPI PMID:21299499 IQ-motif selectivity in human IQGAP2 and IQGAP3: binding of ... | MODIFY | Summary: Refine the IQGAP3 interaction to binding its defined IQ region. Reason: PMID:21299499 uses recombinant human calmodulin and synthetic IQGAP3 IQ peptides to map the interaction to a defined protein region. All four IQ motifs interact in calcium, with motifs 2–4 producing the longer-lived complexes; motif 1 is more transient. GO:0019904 captures this mapped domain recognition more precisely than bare protein binding. The original partner is preserved. The refinement consolidates evidence for an already present term and does not establish intact-complex affinity, a universal calcium requirement, GTPase activity or a new cellular process. Proposed replacements: protein domain specific binding Supporting Evidence: |
| GO:0019901 protein kinase binding | IPI PMID:20668654 Structure of the CaMKIIdelta/calmodulin complex reveals the ... | MODIFY | Summary: The source measures direct binding of human calmodulin to the exact CaMKII isozyme and explains release of kinase autoinhibition. Reason: The source measures direct binding of human calmodulin to the exact CaMKII isozyme and explains release of kinase autoinhibition. Refine the unspecified kinase-binding row to the demonstrated serine/threonine kinase activator activity, preserving the original alpha/delta partner and its experimental evidence. Proposed replacements: protein serine/threonine kinase activator activity Supporting Evidence: |
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Download this section (compressed HTML)Q: Which CALM3-specific expression and local translation patterns determine availability of the shared calmodulin protein at individual cardiac and synaptic targets?
Q: Can the unresolved LYST, tau and substantia-nigra source assays be recovered to distinguish target evidence from abstract-level context?
Q: How do CALM3 variants alter calcium affinity and target-specific gating under endogenous expression, compared with recombinant and overexpression assays?
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