CALM2 encodes calmodulin, a small EF-hand calcium sensor whose canonical protein sequence is identical to those encoded by CALM1 and CALM3. Calcium-dependent conformational changes and target association couple intracellular calcium signals to activation of enzymes such as CaMKII and calcineurin and to regulation of ion channels. Calmodulin supports CaV1.2 calcium-dependent inactivation and controls RyR2-mediated calcium release; it also regulates potassium channels through distinct target interactions. Soluble cytoplasmic and nuclear pools exchange with membrane- and organelle-associated complexes. CALM2 variants can cause severe cardiac arrhythmia, including long-QT syndrome, through altered calcium sensing and channel regulation. The same protein also participates in cell-cycle and synaptic signaling, with gene-specific expression and dosage contributing biological context.
| GO Term | Evidence | Action | Reason |
|---|---|---|---|
| GO:0000922 spindle pole | IDA PMID:16760425 CP110 cooperates with two calcium-binding proteins to regula... | KEEP AS NON CORE | Summary: Calmodulin has a mitotic spindle-pole pool. Reason: The experimental annotation and the independently curated UniProt spindle-pole localization support this contextual pool. The available CP110 paper contains selected Results and Discussion, not the complete localization figures or Methods; retention defers to the curator for that precise assay. It is not a separate core activity. |
| GO:0000922 spindle pole | IEA GO_REF:0000120 | KEEP AS NON CORE | Summary: The spindle-pole mapping is consistent with curated localization. Reason: The combined ARBA and UniProt subcellular-location mapping agrees with the experimental spindle-pole assertion and curated mitotic concentration of calmodulin. It describes a cell-cycle-dependent pool rather than a distinct biochemical core. |
| GO:0002027 regulation of heart rate | IEA GO_REF:0000117 | ACCEPT | Summary: Calmodulin channel regulation contributes directly to heart-rate control. Reason: The ARBA assertion is independently supported by calmodulin-dependent cardiac channel gating and arrhythmia studies. Human CALM2-associated long-QT evidence is distinguished from the CALM1 pedigrees in the original 2012 study; the identical canonical protein supplies the regulatory activity. |
| GO:0002027 regulation of heart rate | IMP PMID:23040497 Mutations in calmodulin cause ventricular tachycardia and su... | ACCEPT | Summary: Cardiac calmodulin dysfunction alters rhythm through channel regulation. Reason: The complete cached abstract identifies CALM1 mutations and impaired calcium binding and RyR2 interaction. Those pedigrees are not CALM2 genetics, but the wild-type protein is identical and independent CALM2 long-QT evidence supports the cardiac role. Retain the experimental protein-function annotation without claiming a CALM2-specific assay in this paper. |
| GO:0005246 calcium channel regulator activity | IDA PMID:20226167 Defective calmodulin binding to the cardiac ryanodine recept... | ACCEPT | Summary: Calmodulin directly regulates the RyR2 calcium-release channel. Reason: The source uses a mouse RyR2-R2474S model and shows that added calmodulin attenuates abnormal calcium sparks. Selected authenticated fuller Results and Methods support the channel-associated mechanism; the canonical cache is abstract-only. This establishes shared-protein regulatory activity, not a human CALM2 mutation experiment. Supporting Evidence: PMID:20226167 CaM attenuated the aberrant increase of Ca(2+) sparks |
| GO:0005246 calcium channel regulator activity | IEA GO_REF:0000117 | ACCEPT | Summary: Calcium-channel regulation is an established calmodulin activity. Reason: The electronic rule agrees with independent RyR2 and CaV1.2 functional evidence. Calmodulin is the calcium-sensing regulator, whereas the channel proteins provide ion conduction. |
| GO:0005509 calcium ion binding | IBA GO_REF:0000033 | ACCEPT | Summary: EF-hand calcium binding is central to the calmodulin sensor. Reason: The cached PAINT table has the exact PTN000549682 calcium-binding IBD. Human calmodulins among descendant evidence provide valid experimental grounding, not circularity. Multiple target-protein calcium-binding studies independently support transfer; the full phylogenetic tree and alignment were not reconstructed. Propagation Review Root cause: NO FAILURE CORE Sources checked: PANTHER:PTN000549682 SUPPORTS TRANSFER Exact node/term IBD inspected in cached PTHR23048 PAINT export. Full tree/MSA and all donor assays were not reconstructed. Independent shared-protein evidence corroborates this assertion; human target descendants are legitimate support. |
| GO:0005509 calcium ion binding | IDA PMID:11807546 Structural basis for the activation of anthrax adenylyl cycl... | ACCEPT | Summary: The exotoxin complex demonstrates calcium-responsive calmodulin binding. Reason: The complete source abstract reports a calcium-dependent conformational switch in calmodulin bound to anthrax edema factor. This directly supports calcium binding by the host protein; the bacterial partner performs adenylate-cyclase catalysis. Supporting Evidence: |
| GO:0005509 calcium ion binding | IDA PMID:23040497 Mutations in calmodulin cause ventricular tachycardia and su... | ACCEPT | Summary: The shared calmodulin protein binds calcium. Reason: The source directly reports compromised calcium binding of CALM1 variants relative to wild type. CALM1 genetic origin does not invalidate the identical wild-type CALM2 protein function; no CALM2-specific pedigree is inferred. Supporting Evidence: |
| GO:0005509 calcium ion binding | IDA PMID:26164367 Distinctive malfunctions of calmodulin mutations associated ... | ACCEPT | Summary: Calcium binding underlies calmodulin regulation of RyR2. Reason: The complete abstract examines arrhythmia-associated calmodulin mutants and their calcium-dependent RyR2 effects. Together with independent direct calcium-binding evidence it supports this biochemical property, without assigning every assayed variant to CALM2. |
| GO:0005509 calcium ion binding | IDA PMID:26969752 Spectrum and Prevalence of CALM1-, CALM2-, and CALM3-Encoded... | ACCEPT | Summary: Calcium-binding changes are measured in the long-QT study. Reason: The source reports reduced calcium affinity and impaired CaV1.2 inactivation for the characterized mutant, with wild-type calmodulin as the comparator. The available body includes CALM2 disease context; variant-specific channel effects are not generalized to every CALM2 allele. Supporting Evidence: |
| GO:0005509 calcium ion binding | IDA PMID:27516456 Novel CPVT-Associated Calmodulin Mutation in CALM3 (CALM3-A1... | ACCEPT | Summary: The CALM3 variant study also informs the identical wild-type protein. Reason: The paper concerns CALM3-A103V and its calcium-dependent functional changes. Its CALM3 genetic association is kept separate from CALM2, while wild-type calmodulin calcium binding is independently established and the experimental annotation is retained at the shared-protein level. |
| GO:0005509 calcium ion binding | IDA PMID:35568036 A family of conserved bacterial virulence factors dampens in... | ACCEPT | Summary: Calmodulin is the calcium sensor targeted by bacterial OspC proteins. Reason: Selected source Results distinguish apo-calmodulin sequestration from calcium-dependent CaMKII activation. The calcium-binding assertion is consistent with this mechanism and direct independent biochemistry; neither OspC catalysis nor its downstream interferon phenotype is assigned to calmodulin. |
| GO:0005509 calcium ion binding | IDA PMID:7607248 A calmodulin-binding sequence in the C-terminus of human car... | ACCEPT | Summary: Calcium-dependent titin association uses the calmodulin sensor. Reason: The complete abstract describes calcium-dependent calmodulin interaction with a human titin kinase-region sequence. Direct calcium-binding studies independently establish the sensor property. Binding does not by itself establish activation of titin kinase. |
| GO:0005509 calcium ion binding | IDA PMID:8631777 Blocking the Ca2+-induced conformational transitions in calm... | ACCEPT | Summary: Human calmodulin calcium binding drives conformational activation. Reason: The human liver calmodulin disulfide-lock experiments reduce calcium affinity and target-enzyme activation, with recovery after reduction. The complete abstract provides direct biochemical support for the calcium-binding mechanism. Supporting Evidence: |
| GO:0005509 calcium ion binding | IEA GO_REF:0000120 | ACCEPT | Summary: The EF-hand mapping matches direct calmodulin biochemistry. Reason: The InterPro and ARBA inference is corroborated by measured calcium binding and calcium-dependent structural transitions. Calcium sensing is integrated into target regulation rather than represented as a redundant stand-alone core. |
| GO:0005513 detection of calcium ion | IBA GO_REF:0000033 | ACCEPT | Summary: Calmodulin detects calcium through a functional conformational switch. Reason: The exact PTN008588809 detection-of-calcium IBD is present in the cached PAINT table. Target experiments connect calcium binding to altered target regulation, supporting inherited sensing rather than merely a passive binding site; human descendant evidence is legitimate. Propagation Review Root cause: NO FAILURE CORE Sources checked: PANTHER:PTN008588809 SUPPORTS TRANSFER Exact node/term IBD inspected in cached PTHR23048 PAINT export. Full tree/MSA and all donor assays were not reconstructed. Independent shared-protein evidence corroborates this assertion; human target descendants are legitimate support. |
| GO:0005513 detection of calcium ion | IEA GO_REF:0000117 | ACCEPT | Summary: Calcium detection is supported independently of the electronic rule. Reason: Calcium-dependent changes in calmodulin conformation enable target-enzyme and channel regulation. This positive biochemical mechanism supports the ARBA sensing assertion. |
| GO:0005513 detection of calcium ion | IMP PMID:23040497 Mutations in calmodulin cause ventricular tachycardia and su... | ACCEPT | Summary: Variant experiments connect calcium sensing with cardiac regulation. Reason: The original CALM1 study links calcium-binding defects to impaired RyR2 interaction. Together with direct conformational experiments it supports the shared calmodulin sensor function; it does not establish CALM2-specific genetics. |
| 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. The canonical calmodulin protein is shared among CALM1/2/3; this interaction evidence is not a CALM2-specific expression or clinical assertion. Proposed replacements: cytoskeletal protein binding 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. The canonical calmodulin protein is shared among CALM1/2/3; this interaction evidence is not a CALM2-specific expression or clinical assertion. Supporting Evidence: |
| 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 CALM2-specific human physiological assay. The canonical calmodulin protein is shared among CALM1/2/3; this interaction evidence is not a CALM2-specific expression or clinical assertion. 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. The canonical calmodulin protein is shared among CALM1/2/3; this interaction evidence is not a CALM2-specific expression or clinical assertion. 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. The canonical calmodulin protein is shared among CALM1/2/3; this interaction evidence is not a CALM2-specific expression or clinical assertion. 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. The canonical calmodulin protein is shared among CALM1/2/3; this interaction evidence is not a CALM2-specific expression or clinical assertion. 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. The canonical calmodulin protein is shared among CALM1/2/3; this interaction evidence is not a CALM2-specific expression or clinical assertion. 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. The canonical calmodulin protein is shared among CALM1/2/3; this interaction evidence is not a CALM2-specific expression or clinical assertion. Supporting Evidence: |
| GO:0005515 protein binding | IPI PMID:21299499 IQ-motif selectivity in human IQGAP2 and IQGAP3: binding of ... | KEEP AS NON CORE | Summary: Retain calmodulin binding to IQGAP2 IQ motifs. Reason: Selected PMID:21299499 Methods and Results describe recombinant human calmodulin and IQGAP2-derived IQ peptides, with calcium-dependent mobility-shift binding assays. These establish the peptide-binding interaction and support the curated full-protein edge. Preserve the original partner; motif-peptide affinities do not establish the affinity or regulatory direction of every intact cellular complex, or confer GTPase activity on calmodulin. The canonical calmodulin protein is shared among CALM1/2/3; this interaction evidence is not a CALM2-specific expression or clinical assertion. Supporting Evidence: |
| GO:0005515 protein binding | IPI PMID:21299499 IQ-motif selectivity in human IQGAP2 and IQGAP3: binding of ... | KEEP AS NON CORE | Summary: Retain calmodulin binding to IQGAP3 IQ motifs. Reason: Selected PMID:21299499 Methods and Results describe recombinant human calmodulin and IQGAP3-derived IQ peptides, with calcium-dependent mobility-shift binding assays. These establish the peptide-binding interaction and support the curated full-protein edge. Preserve the original partner; motif-peptide affinities do not establish the affinity or regulatory direction of every intact cellular complex, or confer GTPase activity on calmodulin. The canonical calmodulin protein is shared among CALM1/2/3; this interaction evidence is not a CALM2-specific expression or clinical assertion. 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. The canonical calmodulin protein is shared among CALM1/2/3; this interaction evidence is not a CALM2-specific expression or clinical assertion. Supporting Evidence: |
| GO:0005634 nucleus | HDA PMID:21630459 Proteomic characterization of the human sperm nucleus. | ACCEPT | Summary: Calmodulin has a supported nuclear pool. Reason: The source is human sperm-nucleus proteomics; its individual target table was not inspected. Independently curated human NFAT:calmodulin nuclear complexes support the broad nuclear location, so retention defers to the experimental curator rather than claiming target-peptide reanalysis or CALM2-specific transcription. |
| GO:0005634 nucleus | IBA GO_REF:0000033 | ACCEPT | Summary: Nuclear calmodulin activity is compatible with the PAINT assertion. Reason: The exact PTN008588804 nuclear IBD was read in the cached PAINT table. Human nuclear calmodulin-complex curation independently supports the compartment. The full tree, alignment and original rat assays were not reconstructed; no inference of failure follows from donor number. Propagation Review Root cause: NO FAILURE CORE Sources checked: PANTHER:PTN008588804 SUPPORTS TRANSFER Exact node/term IBD inspected in cached PTHR23048 PAINT export. Full tree/MSA and all donor assays were not reconstructed. Independent shared-protein evidence corroborates this assertion; human target descendants are legitimate support. Supporting Evidence: Reactome:R-HSA-2730867 Reactome:R-HSA-4551465 |
| GO:0005737 cytoplasm | IBA GO_REF:0000033 | ACCEPT | Summary: Cytoplasmic calmodulin regulation is a central cellular activity. Reason: The cached PTN008588804 cytoplasmic IBD agrees with direct human calmodulin regulatory experiments and curated localization. CALM2 appearing among experimental descendants is valid support rather than circular propagation. Propagation Review Root cause: NO FAILURE CORE Sources checked: PANTHER:PTN008588804 SUPPORTS TRANSFER Exact node/term IBD inspected in cached PTHR23048 PAINT export. Full tree/MSA and all donor assays were not reconstructed. Independent shared-protein evidence corroborates this assertion; human target descendants are legitimate support. |
| GO:0005737 cytoplasm | IDA PMID:27165696 Arrhythmogenic calmodulin mutations impede activation of sma... | ACCEPT | Summary: Cytoplasmic calmodulin can regulate SK channels. Reason: The available source narrative describes transfected HEK-cell SK2 regulation and separate murine-heart physiology; detailed Methods are in unavailable supplemental material. The broad cytoplasmic compartment is independently curated and retained, without claiming a CALM2-specific endogenous localization image. |
| GO:0005737 cytoplasm | TAS PMID:10899953 Calmodulin regulation of basal and agonist-stimulated G prot... | ACCEPT | Summary: Calmodulin can move between membrane-associated and soluble pools. Reason: The complete abstract reports release of calmodulin from plasma membranes in a human opioid-receptor HEK293 model. Together with curated cytoplasmic localization this supports the broad compartment; membrane association does not make calmodulin a transmembrane protein. |
| GO:0005813 centrosome | IBA GO_REF:0000033 | KEEP AS NON CORE | Summary: A centrosomal calmodulin pool contributes to cell-cycle regulation. Reason: The exact PTN008588806 centrosome IBD is present in the cached PAINT export, with human calmodulins as experimental descendants. CP110-complex and independently curated localization evidence support this contextual pool; no full tree or original imaging reanalysis is claimed. Propagation Review Root cause: NO FAILURE NON CORE Sources checked: PANTHER:PTN008588806 SUPPORTS TRANSFER Exact node/term IBD inspected in cached PTHR23048 PAINT export. Full tree/MSA and all donor assays were not reconstructed. Independent shared-protein evidence corroborates this assertion; human target descendants are legitimate support. |
| GO:0005813 centrosome | IDA PMID:16760425 CP110 cooperates with two calcium-binding proteins to regula... | KEEP AS NON CORE | Summary: The CP110 work supports centrosomal calmodulin association. Reason: Direct binding and complex evidence plus curated centrosomal localization support retention. The canonical extraction omits most Results and Methods, so the precise localization assay is retained by curator deference rather than claimed as newly inspected. |
| GO:0005813 centrosome | IEA GO_REF:0000120 | KEEP AS NON CORE | Summary: The centrosome mapping agrees with the experimental record. Reason: ARBA and UniProt subcellular mapping are corroborated by the CP110 study and curated mitotic localization. This contextual compartment is retained without creating another core function. |
| GO:0005819 spindle | IEA GO_REF:0000044 | KEEP AS NON CORE | Summary: Calmodulin is associated with the mitotic spindle. Reason: The UniProt subcellular mapping explicitly describes mitotic spindle localization. This is a regulated cellular pool, consistent with CP110-associated cell-cycle work, rather than a distinct constitutive structural activity. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-9956602 | ACCEPT | Summary: The OspC-binding event uses cytosolic calmodulin. Reason: The preserved Reactome-derived GOA assertion supplies the cytosol compartment. The complete cached reaction summary supplies CALM:OspC3 association context, while independently curated cytoplasmic localization and the primary cellular mechanism corroborate the pool; the summary has no explicit compartment field. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-9956624 | ACCEPT | Summary: Calmodulin participates in a cytosolic OspC3 complex. Reason: Cytosol is the original Reactome-derived GOA compartment, not an explicit field in the cached event summary. The summary describes OspC3-mediated CASP4 modification; calmodulin is a regulatory complex component and does not acquire the bacterial enzyme activity. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-9956667 | ACCEPT | Summary: The CASP4-binding event is consistent with cytosolic calmodulin. Reason: The original curated GOA compartment is retained with independent broad cytoplasmic evidence. The cached reaction text establishes event context but does not independently specify cytosol or identify calmodulin as the modifying enzyme. |
| GO:0005876 spindle microtubule | IDA PMID:16760425 CP110 cooperates with two calcium-binding proteins to regula... | KEEP AS NON CORE | Summary: Calmodulin has a spindle-microtubule-associated pool. Reason: The experimental assertion agrees with curated mitotic spindle localization. Precise target imaging in the CP110 paper was not available in the partial canonical extraction, so retention defers to the curator for this location and does not claim that calmodulin polymerizes microtubules. |
| GO:0005876 spindle microtubule | IEA GO_REF:0000117 | KEEP AS NON CORE | Summary: The spindle-microtubule inference is independently corroborated. Reason: The ARBA assertion agrees with the experimental annotation and curated spindle concentration. It describes a context-specific location rather than a separate structural core. |
| GO:0005886 plasma membrane | TAS PMID:10899953 Calmodulin regulation of basal and agonist-stimulated G prot... | ACCEPT | Summary: Calmodulin associates peripherally with plasma-membrane targets. Reason: The complete abstract explicitly examines calmodulin release from plasma membranes in receptor-transfected HEK293 cells. This supports a target-associated membrane pool while leaving the protein soluble and non-transmembrane. Supporting Evidence: |
| 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: Calmodulin modulates opioid-receptor G-protein coupling. Reason: The complete abstract describes direct receptor-loop interaction, altered coupling and receptor mutants with reduced calmodulin affinity. This is positive regulatory participation in the measured signaling context, retained as non-core without generalizing to every GPCR. Supporting Evidence: |
| GO:0008076 voltage-gated potassium channel complex | IEA GO_REF:0000120 | KEEP AS NON CORE | Summary: Calmodulin is a regulatory subunit of KCNQ potassium-channel complexes. Reason: The independent mouse-brain and transfected-cell study identifies constitutive calmodulin association and functional dependence on the interaction. This supports transfer of the shared-protein complex membership; it is distinct from the calcium-channel core and does not assign potassium permeation to calmodulin. Supporting Evidence: |
| GO:0008179 adenylate cyclase binding | IPI PMID:11807546 Structural basis for the activation of anthrax adenylyl cycl... | KEEP AS NON CORE | Summary: Calmodulin binds the bacterial edema-factor adenylate cyclase. Reason: The source structure and functional description support binding to the exact P40136 partner. The interaction is retained in its pathogen context; the bacterial partner performs nucleotide cyclization. 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: Calmodulin activates anthrax edema factor. Reason: The complete abstract describes the structural basis of activation by host calmodulin. This experimentally supported host-factor activity is retained as non-core rather than treated as an endogenous human adenylate-cyclase core. Supporting Evidence: |
| GO:0010856 adenylate cyclase activator activity | IEA GO_REF:0000117 | KEEP AS NON CORE | Summary: The electronic activator assertion has direct pathogen-context evidence. Reason: The edema-factor complex independently supports calmodulin adenylate-cyclase activation. Retention is bounded to that demonstrated interaction; calmodulin itself is not the cyclase. Supporting Evidence: |
| GO:0010880 regulation of release of sequestered calcium ion into cytosol by sarcoplasmic reticulum | IBA GO_REF:0000033 | ACCEPT | Summary: Calmodulin directly regulates sarcoplasmic-reticulum calcium release. Reason: The exact PTN008588809 release-regulation IBD was read in the cached PAINT table. Independent RyR2 binding and calcium-spark experiments support inherited regulatory participation, with mouse-model and shared-protein limits retained. Propagation Review Root cause: NO FAILURE CORE Sources checked: PANTHER:PTN008588809 SUPPORTS TRANSFER Exact node/term IBD inspected in cached PTHR23048 PAINT export. Full tree/MSA and all donor assays were not reconstructed. Independent shared-protein evidence corroborates this assertion; human target descendants are legitimate support. |
| 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: RyR2-associated calmodulin restrains abnormal calcium release. Reason: The mouse RyR2 knock-in study measures spontaneous calcium sparks and their attenuation by added calmodulin. This is direct channel regulation at the release step, not merely a disease association. 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: RyR2 regulation links calmodulin to cardiac excitation-contraction control. Reason: The source experimentally connects altered calmodulin association with RyR2-mediated release in cardiomyocytes. The calcium-release mechanism supports the curated contraction-regulation process; no separate human CALM2 contractility experiment is claimed. Supporting Evidence: |
| 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 cardiac-release role is supported at the shared-protein level. Reason: The CALM1 pedigree study reports impaired RyR2 interaction, and independent RyR2 functional studies establish the release-regulation mechanism. Retain this process while separating CALM1 variant genetics from CALM2 function. |
| GO:0010881 regulation of cardiac muscle contraction by regulation of the release of sequestered calcium ion | IEA GO_REF:0000117 | ACCEPT | Summary: The cardiac contraction mapping is independently supported. Reason: The electronic assertion agrees with direct calmodulin regulation of RyR2 calcium release. This mechanistic contribution supports the process rather than relying solely on arrhythmia or knockout phenotypes. |
| GO:0016020 membrane | IEA GO_REF:0000107 | ACCEPT | Summary: Calmodulin has target-associated membrane pools. Reason: The mouse ortholog propagation is independently corroborated by human receptor-associated membrane-release experiments and channel-complex biochemistry. Retain the broad compartment without inferring membrane insertion or a specific vesicle topology. |
| GO:0016020 membrane | ISS GO_REF:0000024 | ACCEPT | Summary: The manual membrane transfer matches independent target evidence. Reason: The exact P0DP27 donor is preserved. Human receptor-associated membrane calmodulin provides independent support for the broad location, without claiming the original donor localization experiment was re-read. Supporting Evidence: |
| GO:0019855 calcium channel inhibitor activity | IDA PMID:26969752 Spectrum and Prevalence of CALM1-, CALM2-, and CALM3-Encoded... | ACCEPT | Summary: Calmodulin supplies calcium-dependent inactivation of CaV1.2. Reason: The characterized long-QT variant has reduced calcium affinity and a dominant loss of CaV1.2 inactivation compared with wild type. The data support wild-type channel inhibition; RyR2 and sodium-channel effects differ and are not assumed universal. Supporting Evidence: PMID:26969752 dominant loss of inactivation in CaV1.2 |
| GO:0019901 protein kinase binding | IEA GO_REF:0000117 | KEEP AS NON CORE | Summary: Protein-kinase association is a real component of regulation. Reason: The ARBA binding assertion is supported by direct human CaMKII-calmodulin structures and interaction measurements. The more informative activator activity is already represented separately; this binding row is retained as supporting context. Supporting Evidence: |
| GO:0019901 protein kinase binding | IPI PMID:20668654 Structure of the CaMKIIdelta/calmodulin complex reveals the ... | KEEP AS NON CORE | Summary: Calmodulin binds the preserved CaMKII-delta partner. Reason: The human CaMKII-delta/Ca2+/calmodulin structure and selected binding Methods directly support Q13557 association. Activator activity is represented by existing dedicated rows and the kinase-regulation core. Supporting Evidence: |
| GO:0019901 protein kinase binding | IPI PMID:20668654 Structure of the CaMKIIdelta/calmodulin complex reveals the ... | KEEP AS NON CORE | Summary: Calmodulin binds the preserved CaMKII-alpha partner. Reason: Selected human CaMKII interaction measurements and structures support the source-specific Q9UQM7 binding assertion. Retain this supporting association without transferring kinase catalysis to calmodulin or creating a duplicate binding core. Supporting Evidence: |
| GO:0021762 substantia nigra development | HEP PMID:22926577 Quantitative proteomic analysis of human substantia nigra in... | MARK AS OVER ANNOTATED | Summary: Adult substantia-nigra protein abundance does not establish participation in its development. Reason: GO:0021762 concerns substantia-nigra formation and maturation. The author-posted primary Methods, cohort table and target abundance result were accessed: adult postmortem disease/control proteomics detects calmodulin under P62158. This supports protein presence and abundance differences, but not calmodulin performing a developmental step. The developmental interpretation therefore exceeds the inspected evidence. This source-specific judgment does not categorically reject HEP evidence or establish absence of a developmental role. P62158 is a secondary accession in the CALM2 record, not a wrong-gene identifier; the shared protein sequence prevents gene-of-origin discrimination. Supporting Evidence: |
| GO:0030017 sarcomere | IDA PMID:20226167 Defective calmodulin binding to the cardiac ryanodine recept... | KEEP AS NON CORE | Summary: A sarcomeric RyR2-associated calmodulin pool is supported. Reason: Selected authenticated fuller Methods and Results examine endogenous and labeled calmodulin distribution relative to RyR2 in mouse cardiomyocytes. This supports the curated sarcomeric location with model and reagent limits, rather than claiming a human CALM2-specific localization assay. Supporting Evidence: |
| GO:0030017 sarcomere | IEA GO_REF:0000117 | KEEP AS NON CORE | Summary: The sarcomere inference agrees with the experimental channel-associated pool. Reason: The ARBA location is corroborated by the mouse cardiomyocyte RyR2/calmodulin evidence and preserved experimental assertion. Retain this specialized pool as non-core location context. Supporting Evidence: |
| GO:0031432 titin binding | IEA GO_REF:0000117 | KEEP AS NON CORE | Summary: Calmodulin binds a sequence in human titin. Reason: Independent biochemical evidence supports calcium-dependent binding to the titin kinase-region sequence. The electronic term is retained as a specific interaction, without inferring activation of titin catalysis. Supporting Evidence: |
| GO:0031432 titin binding | IPI PMID:7607248 A calmodulin-binding sequence in the C-terminus of human car... | KEEP AS NON CORE | Summary: The exact Q8WZ42 titin interaction is supported. Reason: The complete abstract establishes calcium-dependent calmodulin binding to the human titin sequence. This is a binding claim; it does not establish that calmodulin activates the associated kinase domain. Supporting Evidence: |
| GO:0031982 vesicle | HDA PMID:19190083 Characterization of exosome-like vesicles released from huma... | KEEP AS NON CORE | Summary: Calmodulin is reported in epithelial exosome-like vesicle preparations. Reason: The source describes proteomic characterization of vesicles from human airway epithelium. Retain the curated HDA association with explicit deference for the uninspected target table; no vesicle-lumen topology or CALM2-specific peptide assignment is claimed. Supporting Evidence: |
| GO:0031982 vesicle | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Broad vesicle association has independent human experimental support. Reason: The P0DP27 ortholog transfer is corroborated by the human vesicle proteomics annotation. The precise donor assay and target table were not re-examined, so retention is limited to broad association and not a constitutive intravesicular pool. Supporting Evidence: |
| GO:0031982 vesicle | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: The manual vesicle transfer is compatible with target evidence. Reason: The exact mouse donor is preserved; independently curated human vesicle proteomics supports the broad location. This does not establish membrane topology or a unique CALM2 expression program. Supporting Evidence: |
| GO:0032465 regulation of cytokinesis | IEA GO_REF:0000117 | KEEP AS NON CORE | Summary: CP110-associated calmodulin contributes to cytokinesis regulation. Reason: The experimental source links calmodulin binding to CP110 with cytokinesis: a binding-defective CP110 mutant promotes failure. This supplies a positive regulatory mechanism beyond generic necessity and supports the electronic process as contextual. 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 binding mechanism supports cytokinesis participation. Reason: The source combines binding, depletion and a calmodulin-binding-deficient CP110 mutant. Selected available Results and Discussion support regulatory cooperation rather than merely a generic proliferation phenotype. The shared protein is not assigned a CALM2-specific transcriptional role. Supporting Evidence: PMID:16760425 expression of a CP110 mutant unable to bind CaM also promotes cytokinesis failure |
| GO:0032991 protein-containing complex | IDA PMID:19855925 Structural analysis of the complex between calmodulin and fu... | KEEP AS NON CORE | Summary: The myelin-basic-protein study establishes a calmodulin complex. Reason: The source describes physical calmodulin-MBP complexes. Retain this broad complex annotation without converting an in-vitro complex into proof of endogenous myelin-sheath localization. The linked correction concerns Figure 5 presentation; corrected images were not quantitatively reanalyzed. Supporting Evidence: |
| GO:0034704 calcium channel complex | IDA PMID:23040497 Mutations in calmodulin cause ventricular tachycardia and su... | ACCEPT | Summary: Calmodulin is a regulatory component of calcium-channel complexes. Reason: The source reports RyR2 interaction; independent RyR2 and CaV1.2 functional evidence supports this general complex membership. CALM1 disease origin in the 2012 study is distinguished from the identical CALM2 protein. |
| GO:0034704 calcium channel complex | IEA GO_REF:0000117 | ACCEPT | Summary: The calcium-channel-complex mapping is independently grounded. Reason: Direct calmodulin-channel interaction and functional regulation corroborate this electronic annotation. Calmodulin contributes regulatory sensing within the complex, while the channel subunit conducts calcium. |
| GO:0043209 myelin sheath | IBA GO_REF:0000033 | KEEP AS NON CORE | Summary: Myelin-sheath localization is supported as a contextual shared-calmodulin pool. Reason: The complete abstract of PMID:19855925 explicitly reports calmodulin and MBP colocalization in myelin sheaths, independently supporting this contextual pool beyond the binding experiments. The exact curated propagation is retained with deference to the localization evidence. The abstract does not specify the imaging species or distinguish CALM2 from the identical CALM1/CALM3 protein; the underlying images and full localization Methods were not inspected. The inspected correction concerns circular-dichroism Figure 5, not a stated withdrawal of the localization finding. Propagation Review Root cause: NO FAILURE NON CORE Sources checked: PANTHER:PTN008588809 SUPPORTS TRANSFER Exact PTN008588809 myelin-sheath IBD was inspected in cached PTHR23048 PAINT. Independent calmodulin/MBP colocalization reported by PMID:19855925 corroborates the contextual pool. Full tree/MSA and localization images were not reconstructed; shared-protein evidence does not independently assign CALM2-specific expression. Supporting Evidence: |
| GO:0043209 myelin sheath | IEA GO_REF:0000120 | KEEP AS NON CORE | Summary: Myelin-sheath localization is supported as a contextual shared-calmodulin pool. Reason: The complete abstract of PMID:19855925 explicitly reports calmodulin and MBP colocalization in myelin sheaths, independently supporting this contextual pool beyond the binding experiments. The exact curated propagation is retained with deference to the localization evidence. The abstract does not specify the imaging species or distinguish CALM2 from the identical CALM1/CALM3 protein; the underlying images and full localization Methods were not inspected. The inspected correction concerns circular-dichroism Figure 5, not a stated withdrawal of the localization finding. Supporting Evidence: |
| GO:0043539 protein serine/threonine kinase activator activity | IDA PMID:35568036 A family of conserved bacterial virulence factors dampens in... | ACCEPT | Summary: Calmodulin activates CaMKII in the source cellular mechanism. Reason: Selected source Results show that OspC-mediated apo-calmodulin sequestration prevents CaMKII activation. Direct structural and biochemical CaMKII evidence independently establishes the activator function; bacterial OspC catalysis is a separate activity. |
| GO:0043539 protein serine/threonine kinase activator activity | IEA GO_REF:0000117 | ACCEPT | Summary: The kinase-activator mapping has direct mechanistic support. Reason: Human CaMKII structures and binding experiments show how calcium-bound calmodulin releases the autoinhibitory configuration. This corroborates the electronic activator assertion without assigning phosphate-transfer catalysis to calmodulin. Supporting Evidence: |
| GO:0043539 protein serine/threonine kinase activator activity | TAS PMID:20668654 Structure of the CaMKIIdelta/calmodulin complex reveals the ... | ACCEPT | Summary: Human CaMKII is activated by calmodulin association. Reason: The source combines structures and biophysical interaction studies of human CaMKII. It directly supports relief of autoinhibition by calmodulin; the exact clone numbering does not create a new CALM2 protein product. Supporting Evidence: PMID:20668654 mechanism of CaMKII activation by calmodulin |
| GO:0044305 calyx of Held | IEA GO_REF:0000120 | KEEP AS NON CORE | Summary: Mouse Calm2 experiments support activity at the calyx of Held. Reason: The complete donor abstract reports calmodulin-2 knockout and synaptic endocytosis measurements at calyx-type terminals. This is positive functional compartment evidence for the shared protein, retained with the mouse-to-human context boundary and no CALM2-specific human expression claim. 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: Calmodulin binds the human NaV1.5 IQ motif. Reason: The source reports an apo-calmodulin/IQ-motif NMR structure for the exact Q14524 partner. This supports transporter binding without turning the isolated-domain structure into an independently measured full-channel gating assay. Supporting Evidence: |
| GO:0044325 transmembrane transporter binding | IPI PMID:23040497 Mutations in calmodulin cause ventricular tachycardia and su... | KEEP AS NON CORE | Summary: Calmodulin interaction with RyR2 is independently supported. Reason: The original abstract reports compromised RyR2 interaction by CALM1 variants, while direct mouse RyR2 studies corroborate association of the shared wild-type protein. Retain exact Q92736 and separate protein binding from CALM2-specific genetic evidence. |
| GO:0048306 calcium-dependent protein binding | IEA GO_REF:0000107 | ACCEPT | Summary: Calcium-dependent target association is a conserved calmodulin mechanism. Reason: Independent human titin and calmodulin conformational studies support calcium-dependent binding despite the uninspected original mouse donor assay. The term does not imply that every calmodulin interaction requires calcium; apo-calmodulin binding also occurs. |
| GO:0048306 calcium-dependent protein binding | ISS GO_REF:0000024 | ACCEPT | Summary: Manual transfer of calcium-dependent binding is independently corroborated. Reason: The exact P0DP27 donor is preserved. Human protein biochemistry supports calcium-dependent target association, while apo-calmodulin complexes remain a distinct valid mode. |
| GO:0050848 regulation of calcium-mediated signaling | ISS GO_REF:0000024 | ACCEPT | Summary: Calmodulin directly regulates calcium-mediated signaling. Reason: Its calcium-dependent activation of kinases and calcineurin and regulation of channels support the transferred broad signaling role. The original acts_upstream_of_or_within qualifier is retained, and the protein is not reduced to a passive substrate. |
| GO:0051592 response to calcium ion | IDA PMID:7607248 A calmodulin-binding sequence in the C-terminus of human car... | ACCEPT | Summary: Calmodulin changes target interactions in response to calcium. Reason: The human titin-binding experiment establishes calcium-dependent association, and independent conformational studies explain the responsive mechanism. This is direct participation in calcium response, not simply calcium-dependent abundance. |
| GO:0055117 regulation of cardiac muscle contraction | IMP PMID:23040497 Mutations in calmodulin cause ventricular tachycardia and su... | ACCEPT | Summary: Calmodulin contributes directly to cardiac contraction regulation. Reason: Channel regulation provides a positive mechanistic basis for the broad cardiac process. CALM1 pedigrees in the original paper are kept separate from CALM2-associated long-QT evidence and from mouse RyR2 functional experiments. |
| GO:0060291 long-term synaptic potentiation | IEA GO_REF:0000117 | KEEP AS NON CORE | Summary: CaMKII activation provides a contextual role in synaptic potentiation. Reason: The electronic LTP assertion is consistent with calmodulin activation of the CaMKII regulatory switch. This is retained as a contextual pathway contribution; the structural study is not represented as a new CALM2-specific human synaptic-plasticity experiment. Supporting Evidence: |
| GO:0060291 long-term synaptic potentiation | TAS PMID:20668654 Structure of the CaMKIIdelta/calmodulin complex reveals the ... | KEEP AS NON CORE | Summary: The CaMKII study supports the curated LTP context. Reason: The paper explicitly places calcium/calmodulin activation of CaMKII in long-term potentiation and resolves the activation mechanism. Retain the TAS process by source-aware curator deference, while distinguishing biochemical structures from direct LTP recordings. Supporting Evidence: |
| GO:0060315 negative regulation of ryanodine-sensitive calcium-release channel activity | IDA PMID:26164367 Distinctive malfunctions of calmodulin mutations associated ... | ACCEPT | Summary: Wild-type calmodulin inhibits RyR2-dependent calcium release. Reason: The complete abstract compares arrhythmia-associated calmodulin mutants in RyR2 regulatory assays. Together with calcium-spark suppression by added wild-type protein it supports negative channel regulation; mutant effects are not assumed identical. |
| GO:0072542 protein phosphatase activator activity | IDA PMID:8631777 Blocking the Ca2+-induced conformational transitions in calm... | ACCEPT | Summary: Calmodulin directly activates the phosphatase calcineurin. Reason: Human calmodulin disulfide locks disrupt calcium-dependent target activation and reduction restores activity. The source directly supports an activator function, while calcineurin performs substrate dephosphorylation. Supporting Evidence: PMID:8631777 loss of ability to activate target enzymes, phosphodiesterase and calcineurin |
| GO:0072542 protein phosphatase activator activity | IEA GO_REF:0000117 | ACCEPT | Summary: The phosphatase-activator mapping agrees with direct experiments. Reason: Human calmodulin activation of calcineurin is independently supported by conformational-lock and recovery experiments. This is its own regulatory function rather than phosphatase catalysis. Supporting Evidence: |
| GO:0097225 sperm midpiece | IEA GO_REF:0000107 | UNDECIDED | Summary: The precise sperm-midpiece assignment remains unresolved. Reason: The available donor lead describes FAM71D localization and interaction with calmodulin, but the complete abstract does not resolve localization of calmodulin itself to the midpiece. The target donor assay was not inspected; a partner location alone is insufficient, and the annotation is not declared false. Supporting Evidence: |
| GO:0097720 calcineurin-mediated signaling | IBA GO_REF:0000033 | ACCEPT | Summary: Calmodulin directly participates in calcineurin signaling. Reason: The cached PAINT table contains the exact PTN008588809 calcineurin-signaling IBD. Human calmodulin activation of calcineurin independently supports inheritance and participation; target descendants provide legitimate experimental grounding. Propagation Review Root cause: NO FAILURE CORE Sources checked: PANTHER:PTN008588809 SUPPORTS TRANSFER Exact node/term IBD inspected in cached PTHR23048 PAINT export. Full tree/MSA and all donor assays were not reconstructed. Independent shared-protein evidence corroborates this assertion; human target descendants are legitimate support. Supporting Evidence: |
| GO:0097720 calcineurin-mediated signaling | IDA PMID:8631777 Blocking the Ca2+-induced conformational transitions in calm... | ACCEPT | Summary: Calmodulin supplies the activator step in calcineurin signaling. Reason: The human calmodulin conformational-lock experiment directly tests calcineurin activation. This identifies the work performed by calmodulin in the pathway, without attributing the phosphatase reaction to it. Supporting Evidence: |
| GO:0097720 calcineurin-mediated signaling | IEA GO_REF:0000117 | ACCEPT | Summary: The calcineurin pathway mapping is experimentally corroborated. Reason: Direct calmodulin-dependent calcineurin activation supports the electronic process annotation. Calcium binding and the activating conformational change are the mechanistic contribution. Supporting Evidence: |
| GO:0099523 presynaptic cytosol | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Mouse Calm2 function supports a presynaptic cytosolic pool. Reason: The source reports calmodulin-2 knockout and rescue of calcium-stimulated endocytosis in mouse synapses. This corroborates activity in the presynaptic compartment; it is not a human CALM2-specific imaging or vesicle-lumen claim. Supporting Evidence: |
| GO:0140238 presynaptic endocytosis | IEA GO_REF:0000120 | KEEP AS NON CORE | Summary: Calmodulin acts as a calcium sensor for presynaptic endocytosis. Reason: The mouse calmodulin-2 knockout phenotype is rescued by wild-type but not calcium-binding-defective protein. The sensor function explains direct regulatory participation beyond necessity, while the anatomical and experimental model boundary is retained. Supporting Evidence: PMID:31628181 calcium stimulates endocytosis by binding with its calcium sensor PKC and calmodulin |
| GO:0141110 transporter inhibitor activity | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Calmodulin suppresses stimulated NCKX4 exchanger activity in a defined context. Reason: Selected Methods and Results use mouse NCKX4 and a chicken CALM2-encoded protein identical to the mammalian protein in HEK cells. Calcium-competent calmodulin suppresses purinergic activation, while basal transport is unaffected; this supports contextual inhibition rather than universal transporter blockade. Supporting Evidence: PMID:33199372 suppressed NCKX4 activation in a time-dependent manner |
| GO:0141110 transporter inhibitor activity | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: The manual transporter-inhibitor transfer has direct protein-mechanism support. Reason: The original mouse donor is preserved. Independent NCKX4 experiments with the identical calmodulin protein support suppression of stimulated transport, with no claim that all transporters or basal exchanger activity are inhibited. Supporting Evidence: |
| 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: Cardiac channel regulation supports the curated electrical-coupling role. Reason: The original experimental annotation is retained through the established calmodulin-dependent regulation of cardiac channels and independent CALM2 long-QT evidence. The cached 2012 abstract reports CALM1 variants; it does not permit reanalysis of a specific intercellular coupling assay or establish CALM2 genetics by itself. |
| GO:1901844 regulation of cell communication by electrical coupling involved in cardiac conduction | IEA GO_REF:0000117 | ACCEPT | Summary: The electronic cardiac-conduction assertion is independently corroborated. Reason: Calmodulin regulates cardiac channel behavior and CALM2 variants can disrupt repolarization. Retain the broad curated regulatory role without assigning calmodulin a gap-junction pore or claiming a newly inspected coupling assay. |
| GO:1902494 catalytic complex | IDA PMID:11807546 Structural basis for the activation of anthrax adenylyl cycl... | KEEP AS NON CORE | Summary: Calmodulin is the regulatory component of the edema-factor catalytic complex. Reason: The structure establishes the host-protein/bacterial-adenylate-cyclase assembly. Complex membership is supported, but catalytic conversion of ATP belongs to edema factor. This pathogen interaction is retained as non-core context. Supporting Evidence: |
| 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 export capacity. Reason: The preserved ortholog-derived process is supported by a calcium-dependent calmodulin effect on stimulated NCKX4 transport. Selected Methods measure exchanger activity in reverse-mode calcium-entry conditions; the normal calcium-efflux interpretation follows exchanger function and curation, not a newly measured physiological export flux. Basal activity was unaffected. Supporting Evidence: |
| GO:1905913 negative regulation of calcium ion export across plasma membrane | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: The manual negative-export transfer is retained with assay bounds. Reason: Independent NCKX4 evidence supports context-dependent exchanger inhibition by the identical calmodulin protein. The assay uses mouse transporter in HEK cells and reverse-mode activity measurements; no universal inhibition of calcium export or human CALM2-specific phenotype is asserted. Supporting Evidence: |
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Download this section (compressed HTML)Q: Which specialized myelin-sheath and sperm-midpiece calmodulin pools are directly supported by the original rodent assays, and how are the identical CALM gene products distinguished?
Q: What target-specific evidence underlies the substantia-nigra developmental annotation, beyond the available adult disease-proteomics abstract?
Q: How do CALM2 expression and dosage influence target occupancy and phenotypic differences among calmodulinopathies despite the identical canonical CALM1, CALM2 and CALM3 protein sequences?
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