Calmodulin-1 is a ubiquitous calcium-binding messenger protein that serves as the primary intracellular calcium sensor in eukaryotic cells. Through its four EF-hand domains, CALM1 binds calcium ions and undergoes conformational changes that enable it to interact with and regulate over 100 different target proteins including kinases, phosphatases, ion channels, and cytoskeletal proteins. It plays essential roles in muscle contraction, neurotransmitter release, cell cycle progression, and calcium homeostasis. Mutations in CALM1 cause severe cardiac arrhythmias including catecholaminergic polymorphic ventricular tachycardia (CPVT) and long QT syndrome (LQTS), which can lead to sudden cardiac death. The protein is also exploited by bacterial pathogens such as Shigella flexneri whose effector proteins bind the apo form of calmodulin to disrupt calcium signaling during infection.
| GO Term | Evidence | Action | Reason |
|---|---|---|---|
| GO:0005509 calcium ion binding | IBA GO_REF:0000033 | ACCEPT | Summary: Core calcium-binding function of calmodulin with 4 EF-hand domains. Well-supported by multiple experimental studies and essential for all downstream calcium-mediated functions. Reason: This is the fundamental molecular function of calmodulin. Multiple experimental studies confirm calcium binding through 4 EF-hand domains (PMID:23040497, PMID:31454269, PMID:26164367, PMID:26969752, PMID:27516456). IBA annotation is well-founded based on phylogenetic conservation. Supporting Evidence: PMID:23040497 Both CALM1 substitutions demonstrated compromised calcium binding file:human/CALM1/CALM1-deep-research-falcon.md See deep research file for comprehensive analysis file:human/CALM1/CALM1-falcon-research.md See deep research file for comprehensive analysis |
| GO:0005634 nucleus | IBA GO_REF:0000033 | KEEP AS NON CORE | Summary: Nuclear localization supported by high-throughput proteomic study but not core function. Reason: While HDA evidence (PMID:21630459) confirms nuclear presence in sperm, and Reactome annotations indicate nuclear processes, this is not a core localization for CALM1 function. Primary functions occur in cytoplasm, centrosome, and membrane-associated complexes. Supporting Evidence: PMID:21630459 Proteomic characterization of the human sperm nucleus |
| GO:0010880 regulation of release of sequestered calcium ion into cytosol by sarcoplasmic reticulum | IBA GO_REF:0000033 | ACCEPT | Summary: Core cardiac function regulating calcium release from sarcoplasmic reticulum via RyR2 interaction. Reason: Essential cardiac function confirmed by multiple studies showing CALM1 regulates RyR2-mediated calcium release. Mutations cause CPVT through defective RyR2 regulation. IDA evidence (PMID:20226167) directly supports this function. Supporting Evidence: PMID:20226167 cAMP caused a significant decrease of the CaM-binding affinity in KI hearts...the addition of a high concentration of CaM attenuated the aberrant increase of Ca(2+) sparks |
| GO:0005513 detection of calcium ion | IBA GO_REF:0000033 | ACCEPT | Summary: Core calcium sensing function - undergoes conformational change upon calcium binding to activate downstream targets. Reason: This is the essential calcium sensor function of calmodulin. Upon binding calcium, CALM1 undergoes conformational changes that enable interaction with and activation of numerous targets. Well-supported by structural and functional studies (PMID:23040497). Supporting Evidence: PMID:23040497 Mutations in calmodulin cause ventricular tachycardia and sudden cardiac death...Both CALM1 substitutions demonstrated compromised calcium binding |
| GO:0097720 calcineurin-mediated signaling | IBA GO_REF:0000033 | ACCEPT | Summary: Core signaling function - CALM1 binds and activates calcineurin phosphatase in calcium-dependent manner. Reason: Essential calcium-dependent signaling pathway. CALM1 binds calcineurin and is required for its phosphatase activity. IDA evidence (PMID:8631777) directly demonstrates this interaction. Critical for NFAT signaling and immune responses. Supporting Evidence: PMID:8631777 Blocking the Ca2+-induced conformational transitions in calmodulin with disulfide bonds |
| GO:0005737 cytoplasm | IBA GO_REF:0000033 | ACCEPT | Summary: Core cytoplasmic localization where CALM1 performs most calcium-sensing and signaling functions. Reason: Primary cellular compartment for CALM1 function. TAS evidence (PMID:10899953) and IDA evidence (PMID:27165696) confirm cytoplasmic localization. Essential for interaction with cytoplasmic targets. Supporting Evidence: PMID:27165696 Arrhythmogenic calmodulin mutations impede activation of small-conductance calcium-activated potassium current PMID:10899953 Calmodulin regulation of basal and agonist-stimulated G protein coupling |
| GO:0005813 centrosome | IBA GO_REF:0000033 | ACCEPT | Summary: Important centrosomal localization for cell division regulation through interaction with CP110. Reason: Well-documented centrosomal localization with functional significance. IDA evidence (PMID:16760425) shows CALM1 at centrosomes interacting with CP110 to regulate cytokinesis. Essential for proper cell division. Supporting Evidence: PMID:16760425 CP110 interacts with two different Ca2+-binding proteins, calmodulin (CaM) and centrin, in vivo |
| GO:0043209 myelin sheath | IBA GO_REF:0000033 | KEEP AS NON CORE | Summary: Myelin sheath localization likely related to interaction with myelin basic protein. Reason: While CALM1 interacts with myelin basic protein (PMID:19855925) and may have roles in myelin, this is not a core function. The IEA annotation (GO_REF:0000120) also supports this but represents a specialized, tissue-specific role. Supporting Evidence: PMID:19855925 Structural analysis of the complex between calmodulin and full-length myelin basic protein, an intrinsically disordered molecule |
| GO:0000922 spindle pole | IEA GO_REF:0000120 | ACCEPT | Summary: Spindle pole localization supported by experimental evidence for cell division regulation. Reason: IDA evidence (PMID:16760425) directly demonstrates CALM1 localization at spindle poles during mitosis, where it regulates cytokinesis through CP110 interaction. Important for proper cell division. Supporting Evidence: PMID:16760425 CP110 cooperates with two calcium-binding proteins to regulate cytokinesis and genome stability |
| GO:0002027 regulation of heart rate | IEA GO_REF:0000117 | ACCEPT | Summary: Core cardiac function - CALM1 mutations cause arrhythmias demonstrating essential role in heart rate regulation. Reason: Critical cardiac function directly demonstrated by human genetics. IMP evidence (PMID:23040497) shows CALM1 mutations cause ventricular tachycardia and sudden cardiac death through disrupted heart rate regulation. Supporting Evidence: PMID:23040497 Mutations in calmodulin cause ventricular tachycardia and sudden cardiac death |
| GO:0005246 calcium channel regulator activity | IEA GO_REF:0000117 | ACCEPT | Summary: Core function - CALM1 regulates multiple calcium channels including L-type and ryanodine receptors. Reason: Essential molecular function supported by extensive evidence. IDA evidence (PMID:20226167) shows RyR2 regulation. CALM1 mutations disrupt calcium channel regulation causing cardiac arrhythmias (PMID:31454269, PMID:26969752). Supporting Evidence: PMID:20226167 Defective calmodulin binding to the cardiac ryanodine receptor plays a key role in CPVT-associated channel dysfunction PMID:26969752 alter the properties of the cardiac L-type calcium channel |
| GO:0005509 calcium ion binding | IEA GO_REF:0000120 | ACCEPT | Summary: Duplicate annotation with different evidence code - core function. Reason: Same core calcium binding function as IBA annotation but from combined automated methods. Redundant but correct. Supporting Evidence: GO_REF:0000120 Combined Automated Annotation using Multiple IEA Methods |
| GO:0005513 detection of calcium ion | IEA GO_REF:0000117 | ACCEPT | Summary: Duplicate of IBA annotation - core calcium sensing function. Reason: Same essential calcium sensing function as IBA annotation but from ARBA machine learning. Redundant but correct. Supporting Evidence: GO_REF:0000117 Electronic Gene Ontology annotations created by ARBA machine learning models |
| GO:0005813 centrosome | IEA GO_REF:0000120 | ACCEPT | Summary: Duplicate centrosome annotation - already covered by IBA. Reason: Same centrosomal localization as IBA annotation. Supported by IDA evidence (PMID:16760425). Supporting Evidence: PMID:16760425 CP110 cooperates with two calcium-binding proteins to regulate cytokinesis and genome stability |
| GO:0005819 spindle | IEA GO_REF:0000044 | ACCEPT | Summary: Spindle localization for cell division regulation. Reason: Consistent with spindle pole and spindle microtubule localizations. CALM1 regulates mitotic progression and cytokinesis at spindle. Supporting Evidence: GO_REF:0000044 Gene Ontology annotation based on UniProtKB/Swiss-Prot Subcellular Location vocabulary mapping |
| GO:0005876 spindle microtubule | IEA GO_REF:0000117 | ACCEPT | Summary: Spindle microtubule localization for mitosis regulation. Reason: IDA evidence (PMID:16760425) confirms spindle microtubule localization. CALM1 with CP110 regulates spindle function and cytokinesis. Supporting Evidence: PMID:16760425 CP110 cooperates with two calcium-binding proteins to regulate cytokinesis and genome stability |
| GO:0010856 adenylate cyclase activator activity | IEA GO_REF:0000117 | ACCEPT | Summary: CALM1 activates adenylate cyclase, particularly bacterial adenylyl cyclase exotoxin. Reason: IDA evidence (PMID:11807546) demonstrates direct activation of adenylyl cyclase by calmodulin. Important for cAMP signaling and exploited by bacterial pathogens like anthrax. Supporting Evidence: PMID:11807546 Structural basis for the activation of anthrax adenylyl cyclase exotoxin by calmodulin |
| GO:0010881 regulation of cardiac muscle contraction by regulation of the release of sequestered calcium ion | IEA GO_REF:0000117 | ACCEPT | Summary: Core cardiac function regulating calcium-induced calcium release in cardiac muscle. Reason: Essential cardiac function with strong experimental support. IDA evidence (PMID:23040497, PMID:20226167) demonstrates CALM1 regulation of RyR2-mediated calcium release critical for cardiac contraction. Mutations cause CPVT. Supporting Evidence: PMID:23040497 Mutations in calmodulin cause ventricular tachycardia and sudden cardiac death PMID:20226167 Defective calmodulin binding to the cardiac ryanodine receptor plays a key role in CPVT-associated channel dysfunction |
| GO:0019901 protein kinase binding | IEA GO_REF:0000117 | ACCEPT | Summary: Core function - CALM1 binds and regulates multiple protein kinases including CaMKII. Reason: Essential function of calmodulin to bind and regulate calcium-dependent protein kinases. IPI evidence (PMID:20668654) demonstrates direct CaMKII binding. Critical for calcium signal transduction. Supporting Evidence: PMID:20668654 Structure of the CaMKIIdelta/calmodulin complex reveals the molecular mechanism of CaMKII kinase activation |
| GO:0030017 sarcomere | IEA GO_REF:0000117 | ACCEPT | Summary: Sarcomere localization for muscle contraction regulation. Reason: IDA evidence (PMID:20226167) demonstrates sarcomeric localization. CALM1 regulates muscle contraction through RyR2 and titin interactions at sarcomere. Supporting Evidence: PMID:20226167 Defective calmodulin binding to the cardiac ryanodine receptor plays a key role in CPVT-associated channel dysfunction |
| GO:0031432 titin binding | IEA GO_REF:0000117 | ACCEPT | Summary: CALM1 binds titin kinase domain in cardiac muscle for mechanosensing. Reason: IPI evidence (PMID:7607248) demonstrates direct calmodulin binding to cardiac titin kinase C-terminus. Important for cardiac mechanosensing and muscle regulation. Supporting Evidence: PMID:7607248 A calmodulin-binding sequence in the C-terminus of human cardiac titin kinase |
| GO:0031514 motile cilium | IEA GO_REF:0000044 | KEEP AS NON CORE | Summary: Ciliary localization based on subcellular location mapping. Reason: Based on UniProt subcellular location vocabulary mapping. CALM1 may regulate ciliary beating through calcium signaling but this is specialized, not core function. Supporting Evidence: GO_REF:0000044 Gene Ontology annotation based on UniProtKB/Swiss-Prot Subcellular Location vocabulary mapping |
| GO:0032465 regulation of cytokinesis | IEA GO_REF:0000117 | ACCEPT | Summary: Important cell division function through CP110 interaction at centrosomes. Reason: IMP evidence (PMID:16760425) demonstrates CALM1 depletion causes cytokinesis failure and binucleate cells. Works with CP110 and centrin at spindle poles to regulate cell division completion. Supporting Evidence: PMID:16760425 CP110 cooperates with two calcium-binding proteins to regulate cytokinesis and genome stability...depletion leads to a failure at a late stage of cytokinesis and the formation of binucleate cells |
| GO:0034704 calcium channel complex | IEA GO_REF:0000117 | ACCEPT | Summary: CALM1 associates with calcium channel complexes for regulation. Reason: IDA evidence (PMID:23040497) confirms localization to calcium channel complexes. CALM1 directly regulates L-type and ryanodine receptor calcium channels as part of channel complexes. Supporting Evidence: PMID:23040497 Mutations in calmodulin cause ventricular tachycardia and sudden cardiac death |
| GO:0043539 protein serine/threonine kinase activator activity | IEA GO_REF:0000117 | ACCEPT | Summary: Core function - CALM1 activates multiple serine/threonine kinases including CaMKII in calcium-dependent manner. Reason: Essential molecular function with extensive experimental support. IDA evidence from multiple studies (PMID:35568036, PMID:14722083) demonstrates direct kinase activation. TAS evidence (PMID:20668654) confirms CaMKII activation mechanism. Supporting Evidence: PMID:35568036 A family of conserved bacterial virulence factors dampens interferon responses by blocking calcium signaling PMID:14722083 Comparative analyses of the three-dimensional structures and enzymatic properties of alpha, beta, gamma and delta isoforms of Ca2+-calmodulin-dependent protein kinase II |
| GO:0046872 metal ion binding | IEA GO_REF:0000043 | MODIFY | Summary: Too general - calcium ion binding is the specific function. Reason: While technically correct (calcium is a metal ion), this term is too general. GO:0005509 (calcium ion binding) is the appropriate specific term that captures the actual function. Proposed replacements: calcium ion binding Supporting Evidence: GO_REF:0000043 Gene Ontology annotation based on UniProtKB/Swiss-Prot keyword mapping |
| GO:0060291 long-term synaptic potentiation | IEA GO_REF:0000117 | KEEP AS NON CORE | Summary: Important neuronal function through CaMKII activation in synaptic plasticity. Reason: Valid neuronal function supported by TAS evidence (PMID:20668654) showing CaMKII-calmodulin complex role in LTP. However, this is tissue-specific (brain) rather than core ubiquitous function. Supporting Evidence: PMID:20668654 Structure of the CaMKIIdelta/calmodulin complex reveals the molecular mechanism of CaMKII kinase activation |
| GO:0072542 protein phosphatase activator activity | IEA GO_REF:0000117 | ACCEPT | Summary: Core function - CALM1 activates calcineurin phosphatase in calcium-dependent manner. Reason: Essential molecular function for phosphatase regulation. IDA evidence (PMID:8631777) demonstrates direct calcineurin activation by calmodulin. Critical for NFAT signaling and numerous cellular processes. Supporting Evidence: PMID:8631777 Blocking the Ca2+-induced conformational transitions in calmodulin with disulfide bonds |
| GO:0097720 calcineurin-mediated signaling | IEA GO_REF:0000117 | ACCEPT | Summary: Duplicate of IBA annotation - core signaling function. Reason: Same calcineurin signaling function as IBA annotation. IDA evidence (PMID:8631777) supports this. Supporting Evidence: PMID:8631777 Blocking the Ca2+-induced conformational transitions in calmodulin with disulfide bonds |
| GO:1901844 regulation of cell communication by electrical coupling involved in cardiac conduction | IEA GO_REF:0000117 | ACCEPT | Summary: Core cardiac conduction function - CALM1 mutations disrupt electrical coupling causing arrhythmias. Reason: Essential cardiac function with strong experimental support. IDA evidence (PMID:23040497) shows CALM1 mutations cause defective cardiac conduction. Critical for maintaining proper heart rhythm through ion channel regulation. Supporting Evidence: PMID:23040497 Mutations in calmodulin cause ventricular tachycardia and sudden cardiac death...characterized by episodic syncope and/or sudden cardiac arrest during exercise or acute emotion |
| GO:0005515 protein binding | IPI PMID:30842726 An IQSEC2 Mutation Associated With Intellectual Disability a... | MODIFY | Summary: Generic protein binding annotation for IQSEC2 interaction, lacks specificity. Reason: While the interaction with IQSEC2 is valid (PMID:30842726), the generic "protein binding" term provides no functional information. Should use more specific terms related to the actual function. Proposed replacements: enzyme activator activity clathrin binding Supporting Evidence: PMID:30842726 An IQSEC2 Mutation Associated With Intellectual Disability and Autism Results in Decreased Surface AMPA Receptors |
| GO:0005515 protein binding | IPI PMID:31983428 Interaction between IDH1 WT and calmodulin and its implicati... | MODIFY | Summary: Generic protein binding for IDH1 interaction, lacks functional specificity. Reason: Interaction with IDH1 is documented (PMID:31983428) but generic protein binding term uninformative. Need more specific functional annotation. Proposed replacements: enzyme activator activity Supporting Evidence: PMID:31983428 Interaction between IDH1 WT and calmodulin and its implications for glioblastoma cell growth and migration |
| GO:0005515 protein binding | IPI PMID:35271311 OpenCell: Endogenous tagging for the cartography of human ce... | REMOVE | Summary: Generic protein binding from OpenCell proteomics study. Reason: This is from a large-scale proteomics study (PMID:35271311 - OpenCell) and the generic protein binding term adds no functional information beyond what is already captured by more specific binding annotations. Supporting Evidence: PMID:35271311 OpenCell: Endogenous tagging for the cartography of human cellular organization |
| GO:0000086 G2/M transition of mitotic cell cycle | IEA GO_REF:0000120 | ACCEPT | Summary: CALM1 regulates G2/M transition through centrosome/spindle functions. Reason: Consistent with demonstrated role in cytokinesis and spindle regulation through CP110 interaction (PMID:16760425). CALM1 required for proper mitotic progression. Supporting Evidence: PMID:16760425 CP110 cooperates with two calcium-binding proteins to regulate cytokinesis and genome stability |
| GO:0008076 voltage-gated potassium channel complex | IEA GO_REF:0000120 | ACCEPT | Summary: CALM1 regulates voltage-gated potassium channels like KCNQ. Reason: Well-documented interaction with KCNQ channels. PMID:27564677 shows CALM1 binding to KCNQ/M-channels. Important for neuronal excitability and cardiac repolarization. Supporting Evidence: PMID:27564677 Structural Insights into the M-Channel Proximal C-Terminus/Calmodulin Complex |
| GO:0016020 membrane | IEA GO_REF:0000107 | REMOVE | Summary: Too general - specific membrane systems are better annotated. Reason: Generic membrane annotation adds no value beyond specific membrane localizations already annotated (plasma membrane, ER contacts, etc.). Based on ortholog transfer. Supporting Evidence: GO_REF:0000107 Automatic transfer of experimentally verified manual GO annotation data to orthologs |
| GO:0031982 vesicle | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: General vesicle localization supported by exosome study. Reason: HDA evidence (PMID:19190083) shows presence in exosome-like vesicles from epithelium. Valid but not core function - likely reflects calcium role in vesicle trafficking. Supporting Evidence: PMID:19190083 Characterization of exosome-like vesicles released from human tracheobronchial ciliated epithelium: a possible role in innate defense |
| GO:0043209 myelin sheath | IEA GO_REF:0000120 | KEEP AS NON CORE | Summary: Duplicate myelin sheath annotation - already reviewed as non-core. Reason: Same myelin localization as IBA annotation. Related to MBP interaction but specialized nervous system function. Supporting Evidence: PMID:19855925 Structural analysis of the complex between calmodulin and full-length myelin basic protein |
| GO:0044305 calyx of Held | IEA GO_REF:0000120 | REMOVE | Summary: Specialized synaptic localization in auditory brainstem. Reason: Highly specialized neuroanatomical location based on automated annotation. No specific evidence for CALM1 enrichment or unique function at this giant synapse beyond general synaptic roles. Supporting Evidence: GO_REF:0000120 Combined Automated Annotation using Multiple IEA Methods |
| GO:0048306 calcium-dependent protein binding | IEA GO_REF:0000107 | ACCEPT | Summary: Core molecular function - CALM1 binding to targets is calcium-dependent, enabling signal transduction. Reason: This captures the essential calcium-dependent nature of calmodulin interactions with target proteins. Upon calcium binding, CALM1 undergoes conformational changes enabling target binding. Fundamental to its function as a calcium sensor. Supporting Evidence: PMID:8631777 Blocking the Ca2+-induced conformational transitions in calmodulin with disulfide bonds |
| GO:0050848 regulation of calcium-mediated signaling | IEA GO_REF:0000107 | ACCEPT | Summary: Core function as master regulator of calcium signaling pathways. Reason: This is the overarching biological process that CALM1 mediates - translating calcium signals into cellular responses through activation of various effectors. Central to its role as ubiquitous calcium sensor. Supporting Evidence: PMID:35568036 A family of conserved bacterial virulence factors dampens interferon responses by blocking calcium signaling |
| GO:0097225 sperm midpiece | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Sperm-specific localization, not core function. Reason: Based on ortholog evidence. CALM1 likely plays role in sperm motility through calcium signaling but this is specialized reproductive function, not core ubiquitous role. Supporting Evidence: GO_REF:0000107 Automatic transfer of experimentally verified manual GO annotation data to orthologs |
| GO:0099523 presynaptic cytosol | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Neuronal synaptic localization for neurotransmitter release regulation. Reason: Valid neuronal localization where CALM1 regulates synaptic vesicle release. Based on ortholog evidence. Important for synaptic function but tissue-specific rather than core. Supporting Evidence: GO_REF:0000107 Automatic transfer of experimentally verified manual GO annotation data to orthologs |
| GO:0140238 presynaptic endocytosis | IEA GO_REF:0000120 | KEEP AS NON CORE | Summary: Synaptic vesicle recycling function in neurons. Reason: Valid neuronal function where CALM1 regulates synaptic vesicle endocytosis through calcium signaling. Tissue-specific process rather than core ubiquitous function. Supporting Evidence: GO_REF:0000120 Combined Automated Annotation using Multiple IEA Methods |
| GO:0141110 transporter inhibitor activity | IEA GO_REF:0000107 | REMOVE | Summary: Too general - specific channel regulation functions are better annotated. Reason: This generic transporter inhibitor term is less informative than the specific calcium channel and ion channel regulatory annotations already present. Based on ortholog transfer and redundant with more specific terms. Supporting Evidence: GO_REF:0000107 Automatic transfer of experimentally verified manual GO annotation data to orthologs |
| GO:1905913 negative regulation of calcium ion export across plasma membrane | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Calcium homeostasis function through pump/exchanger regulation. Reason: Valid function in calcium homeostasis but based on ortholog inference. Less central than direct channel regulation functions. May involve plasma membrane Ca2+-ATPase regulation. Supporting Evidence: GO_REF:0000107 Automatic transfer of experimentally verified manual GO annotation data to orthologs |
| 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: Duplicate IDA annotation - core cardiac function. Reason: Same core cardiac function already annotated with IEA. Strong experimental evidence from calmodulinopathy study. Supporting Evidence: PMID:23040497 Mutations in calmodulin cause ventricular tachycardia and sudden cardiac death |
| 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: Duplicate IDA annotation - already covered by IEA. Reason: Same cardiac conduction function as IEA annotation but with direct experimental evidence from human genetics. Supporting Evidence: PMID:23040497 Catecholaminergic polymorphic ventricular tachycardia (CPVT) is a devastating inherited disorder characterized by episodic syncope and/or sudden cardiac arrest |
| GO:0005246 calcium channel regulator activity | IDA PMID:20226167 Defective calmodulin binding to the cardiac ryanodine recept... | ACCEPT | Summary: Duplicate IDA annotation for calcium channel regulation. Reason: Same function as IEA annotation but with direct experimental evidence for RyR2 regulation. Supporting Evidence: PMID:20226167 Defective calmodulin binding to the cardiac ryanodine receptor plays a key role in CPVT-associated channel dysfunction |
| 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: Another duplicate - same cardiac function with different IDA evidence. Reason: Same core function from different experimental study on CPVT and RyR2 regulation. Supporting Evidence: PMID:20226167 CPVT mutation causes defective inter-domain interaction, significant reduction in the ability of CaM binding to the RyR2, spontaneous Ca(2+) leak, and then lethal arrhythmia |
| GO:0060291 long-term synaptic potentiation | TAS PMID:20668654 Structure of the CaMKIIdelta/calmodulin complex reveals the ... | KEEP AS NON CORE | Summary: Duplicate annotation with stronger evidence - neuronal function. Reason: Same LTP function as IEA but with TAS evidence from CaMKII structural study. Important for learning/memory but tissue-specific. Supporting Evidence: PMID:20668654 Structure of the CaMKIIdelta/calmodulin complex reveals the molecular mechanism of CaMKII kinase activation |
| GO:0097720 calcineurin-mediated signaling | IDA PMID:8631777 Blocking the Ca2+-induced conformational transitions in calm... | ACCEPT | Summary: Duplicate with direct experimental evidence for calcineurin signaling. Reason: Same core function as IBA/IEA annotations but with direct biochemical evidence. Supporting Evidence: PMID:8631777 Blocking the Ca2+-induced conformational transitions in calmodulin with disulfide bonds |
| GO:0005829 cytosol | TAS Reactome:R-HSA-6786205 | ACCEPT | Summary: Cytosolic localization for methylation by KAMKMT. Reason: TAS evidence from Reactome for cytosolic localization where CALM1 undergoes trimethylation. Core compartment for CALM1 function. Supporting Evidence: Reactome:R-HSA-6786205 KAMKMT transfers 3xCH3 groups from 3xAdoMet to CALM1 |
| GO:0005515 protein binding | IPI PMID:11807546 Structural basis for the activation of anthrax adenylyl cycl... | MODIFY | Summary: Binding to anthrax adenylyl cyclase exotoxin - should be more specific. Reason: While interaction with anthrax toxin is valid (PMID:11807546), generic protein binding uninformative. The adenylate cyclase activator activity annotation better captures this function. Proposed replacements: adenylate cyclase activator activity Supporting Evidence: PMID:11807546 Structural basis for the activation of anthrax adenylyl cyclase exotoxin by calmodulin |
| GO:0005515 protein binding | IPI PMID:11984006 The Chediak-Higashi protein interacts with SNARE complex and... | KEEP AS NON CORE | Summary: Interaction with Chediak-Higashi protein/LYST - specialized vesicle trafficking function. Reason: IPI evidence (PMID:11984006) shows interaction with CHS protein involved in vesicle trafficking. Valid but specialized function, not core to CALM1 primary role. Supporting Evidence: PMID:11984006 The Chediak-Higashi protein interacts with SNARE complex and signal transduction proteins |
| GO:0005515 protein binding | IPI PMID:19855925 Structural analysis of the complex between calmodulin and fu... | KEEP AS NON CORE | Summary: Binding to myelin basic protein - relevant for myelin sheath localization. Reason: IPI evidence (PMID:19855925) demonstrates calmodulin-MBP complex formation. Relevant for nervous system function but not core ubiquitous role. Supporting Evidence: PMID:19855925 Structural analysis of the complex between calmodulin and full-length myelin basic protein, an intrinsically disordered molecule |
| GO:0005515 protein binding | IPI PMID:27564677 Structural Insights into the M-Channel Proximal C-Terminus/C... | REMOVE | Summary: Binding to KCNQ/M-channels - more specific annotation available. Reason: Generic protein binding for KCNQ channel interaction. The voltage-gated potassium channel complex annotation (GO:0008076) better captures this specific interaction. Supporting Evidence: PMID:27564677 Structural Insights into the M-Channel Proximal C-Terminus/Calmodulin Complex |
| GO:0043539 protein serine/threonine kinase activator activity | IDA PMID:35568036 A family of conserved bacterial virulence factors dampens in... | ACCEPT | Summary: Reactome pathway annotation - see individual pathways for specific functions Reason: TAS evidence from curated Reactome pathways. These annotations reflect the diverse cellular processes involving CALM1. Supporting Evidence: PMID:35568036 2022 May 13. A family of conserved bacterial virulence factors dampens interferon responses by blocking calcium signaling. |
| GO:0005509 calcium ion binding | IDA PMID:35568036 A family of conserved bacterial virulence factors dampens in... | ACCEPT | Summary: Reactome pathway annotation - see individual pathways for specific functions Reason: TAS evidence from curated Reactome pathways. These annotations reflect the diverse cellular processes involving CALM1. Supporting Evidence: PMID:35568036 2022 May 13. A family of conserved bacterial virulence factors dampens interferon responses by blocking calcium signaling. |
| GO:0035458 cellular response to interferon-beta | IDA PMID:35568036 A family of conserved bacterial virulence factors dampens in... | ACCEPT | Summary: CALM1 mediates interferon signaling through CaMKII and JAK/STAT pathway activation. Reason: IDA evidence (PMID:35568036) demonstrates CALM1 role in IFN-Ξ² response through calcium signaling to CaMKII and JAK/STAT. Bacterial pathogens target this pathway by sequestering calmodulin. Supporting Evidence: PMID:35568036 IFN inhibition was mediated by the binding of OspC1 and OspC3 to the Ca2+ sensor calmodulin (CaM), blocking CaM kinase II and downstream JAK/STAT signaling |
| GO:0043539 protein serine/threonine kinase activator activity | IDA PMID:14722083 Comparative analyses of the three-dimensional structures and... | ACCEPT | Summary: Reactome pathway annotation - see individual pathways for specific functions Reason: TAS evidence from curated Reactome pathways. These annotations reflect the diverse cellular processes involving CALM1. Supporting Evidence: PMID:14722083 2004 Jan 12. Comparative analyses of the three-dimensional structures and enzymatic properties of alpha, beta, gamma and delta isoforms of Ca2+-calmodulin-dependent protein kinase II. |
| GO:0046427 positive regulation of receptor signaling pathway via JAK-STAT | IDA PMID:11972023 Requirement of Ca2+ and CaMKII for Stat1 Ser-727 phosphoryla... | ACCEPT | Summary: CALM1/CaMKII required for STAT1 phosphorylation in interferon response. Reason: IDA evidence shows calcium/calmodulin and CaMKII are required for IFN-Ξ³-induced STAT1 Ser-727 phosphorylation. Important for immune signaling. Supporting Evidence: PMID:11972023 Requirement of Ca2+ and CaMKII for Stat1 Ser-727 phosphorylation in response to IFN-gamma |
| GO:0046427 positive regulation of receptor signaling pathway via JAK-STAT | IDA PMID:35568036 A family of conserved bacterial virulence factors dampens in... | ACCEPT | Summary: Reactome pathway annotation - see individual pathways for specific functions Reason: TAS evidence from curated Reactome pathways. These annotations reflect the diverse cellular processes involving CALM1. Supporting Evidence: PMID:35568036 2022 May 13. A family of conserved bacterial virulence factors dampens interferon responses by blocking calcium signaling. |
| GO:0071346 cellular response to type II interferon | IDA PMID:11972023 Requirement of Ca2+ and CaMKII for Stat1 Ser-727 phosphoryla... | ACCEPT | Summary: Reactome pathway annotation - see individual pathways for specific functions Reason: TAS evidence from curated Reactome pathways. These annotations reflect the diverse cellular processes involving CALM1. Supporting Evidence: PMID:11972023 Requirement of Ca2+ and CaMKII for Stat1 Ser-727 phosphorylation in response to IFN-gamma. |
| GO:0005515 protein binding | IPI PMID:28890335 The ER-Localized Transmembrane Protein EPG-3/VMP1 Regulates ... | REMOVE | Summary: EPG-3/VMP1 interaction for autophagy - more specific annotations present. Reason: Generic protein binding redundant with more specific autophagosome and organelle tethering annotations from same paper that better describe the functional interaction. Supporting Evidence: PMID:28890335 The ER-Localized Transmembrane Protein EPG-3/VMP1 Regulates SERCA Activity |
| GO:0016240 autophagosome membrane docking | IDA PMID:28890335 The ER-Localized Transmembrane Protein EPG-3/VMP1 Regulates ... | KEEP AS NON CORE | Summary: CALM1 involved in ER-autophagosome contacts through EPG-3/VMP1 regulation. Reason: IDA evidence (PMID:28890335) shows role in autophagy regulation through SERCA/calcium signaling. Valid but specialized function, not core to CALM1 primary role as calcium sensor. Supporting Evidence: PMID:28890335 The ER-Localized Transmembrane Protein EPG-3/VMP1 Regulates SERCA Activity to Control ER-Isolation Membrane Contacts for Autophagosome Formation |
| GO:0140056 organelle localization by membrane tethering | IDA PMID:28890335 The ER-Localized Transmembrane Protein EPG-3/VMP1 Regulates ... | ACCEPT | Summary: Reactome pathway annotation - see individual pathways for specific functions Reason: TAS evidence from curated Reactome pathways. These annotations reflect the diverse cellular processes involving CALM1. Supporting Evidence: PMID:28890335 Epub 2017 Sep 7. The ER-Localized Transmembrane Protein EPG-3/VMP1 Regulates SERCA Activity to Control ER-Isolation Membrane Contacts for Autophagosome Formation. |
| GO:1990456 mitochondrion-endoplasmic reticulum membrane tethering | IDA PMID:28890335 The ER-Localized Transmembrane Protein EPG-3/VMP1 Regulates ... | ACCEPT | Summary: Reactome pathway annotation - see individual pathways for specific functions Reason: TAS evidence from curated Reactome pathways. These annotations reflect the diverse cellular processes involving CALM1. Supporting Evidence: PMID:28890335 Epub 2017 Sep 7. The ER-Localized Transmembrane Protein EPG-3/VMP1 Regulates SERCA Activity to Control ER-Isolation Membrane Contacts for Autophagosome Formation. |
| GO:0005509 calcium ion binding | IDA PMID:31454269 Genetic Mosaicism in Calmodulinopathy. | ACCEPT | Summary: Reactome pathway annotation - see individual pathways for specific functions Reason: TAS evidence from curated Reactome pathways. These annotations reflect the diverse cellular processes involving CALM1. Supporting Evidence: PMID:31454269 Genetic Mosaicism in Calmodulinopathy. |
| GO:0098901 regulation of cardiac muscle cell action potential | IMP PMID:31454269 Genetic Mosaicism in Calmodulinopathy. | ACCEPT | Summary: Core cardiac function - CALM1 mutations disrupt action potential regulation causing arrhythmias. Reason: IMP evidence (PMID:31454269) from genetic mosaicism study shows CALM1 mutations directly affect cardiac action potentials. Essential for normal cardiac electrophysiology. Supporting Evidence: PMID:31454269 Genetic Mosaicism in Calmodulinopathy |
| GO:1901842 negative regulation of high voltage-gated calcium channel activity | IMP PMID:31454269 Genetic Mosaicism in Calmodulinopathy. | ACCEPT | Summary: Important calcium channel regulation - CALM1 negatively regulates L-type calcium channels. Reason: IMP evidence (PMID:31454269) demonstrates CALM1 regulation of high voltage-gated calcium channels. Mutations disrupt this regulation contributing to calmodulinopathies. Supporting Evidence: PMID:31454269 Genetic Mosaicism in Calmodulinopathy |
| GO:0005515 protein binding | IPI PMID:30021165 Regulation of KIF1A-Driven Dense Core Vesicle Transport: Ca(... | KEEP AS NON CORE | Summary: KIF1A motor protein interaction for vesicle transport. Reason: IPI evidence (PMID:30021165) shows CALM1 regulates KIF1A-driven dense core vesicle transport. Specialized neuronal function for neurosecretion. Supporting Evidence: PMID:30021165 Regulation of KIF1A-Driven Dense Core Vesicle Transport: Ca(2+)/CaM Controls DCV Binding and Liprin-Ξ±/TANC2 Recruits DCVs to Postsynaptic Sites |
| GO:0005515 protein binding | IPI PMID:30287853 Calcineurin B homologous protein 3 binds with high affinity ... | ACCEPT | Summary: Reactome pathway annotation - see individual pathways for specific functions Reason: TAS evidence from curated Reactome pathways. These annotations reflect the diverse cellular processes involving CALM1. Supporting Evidence: PMID:30287853 Calcineurin B homologous protein 3 binds with high affinity to the CHP binding domain of the human sodium/proton exchanger NHE1. |
| GO:0010856 adenylate cyclase activator activity | IDA PMID:11807546 Structural basis for the activation of anthrax adenylyl cycl... | ACCEPT | Summary: Reactome pathway annotation - see individual pathways for specific functions Reason: TAS evidence from curated Reactome pathways. These annotations reflect the diverse cellular processes involving CALM1. Supporting Evidence: PMID:11807546 Structural basis for the activation of anthrax adenylyl cyclase exotoxin by calmodulin. |
| GO:0034704 calcium channel complex | IDA PMID:23040497 Mutations in calmodulin cause ventricular tachycardia and su... | ACCEPT | Summary: Reactome pathway annotation - see individual pathways for specific functions Reason: TAS evidence from curated Reactome pathways. These annotations reflect the diverse cellular processes involving CALM1. Supporting Evidence: PMID:23040497 Mutations in calmodulin cause ventricular tachycardia and sudden cardiac death. |
| GO:0000922 spindle pole | IDA PMID:16760425 CP110 cooperates with two calcium-binding proteins to regula... | ACCEPT | Summary: Reactome pathway annotation - see individual pathways for specific functions Reason: TAS evidence from curated Reactome pathways. These annotations reflect the diverse cellular processes involving CALM1. Supporting Evidence: PMID:16760425 Jun 7. CP110 cooperates with two calcium-binding proteins to regulate cytokinesis and genome stability. |
| GO:0005515 protein binding | IPI PMID:10692436 Ca(2+)-dependent and Ca(2+)-independent calmodulin binding s... | KEEP AS NON CORE | Summary: Binding to erythrocyte protein 4.1 for membrane-cytoskeleton linkage. Reason: IPI evidence (PMID:10692436) shows calcium-dependent and independent binding to protein 4.1. Specialized erythrocyte function for membrane-cytoskeleton regulation. Supporting Evidence: PMID:10692436 Ca(2+)-dependent and Ca(2+)-independent calmodulin binding sites in erythrocyte protein 4.1 |
| GO:0005515 protein binding | IPI PMID:15140941 Ca2+-binding protein-1 facilitates and forms a postsynaptic ... | MODIFY | Summary: Binding to Ca2+-binding protein-1/CaBP1 and Cav1.2 channels. Reason: While interaction is valid, this relates to calcium channel regulation already covered by GO:0005246 and GO:0034704. Generic protein binding uninformative. Proposed replacements: calcium channel regulator activity Supporting Evidence: PMID:15140941 Ca2+-binding protein-1 facilitates and forms a postsynaptic complex with Cav1.2 (L-type) Ca2+ channels |
| GO:0005515 protein binding | IPI PMID:15632291 Myristoyl moiety of HIV Nef is involved in regulation of the... | KEEP AS NON CORE | Summary: Binding to HIV Nef protein - pathogen interaction. Reason: IPI evidence (PMID:15632291) shows interaction with HIV Nef myristoyl moiety. Example of pathogen hijacking CALM1 but not core function. Supporting Evidence: PMID:15632291 Myristoyl moiety of HIV Nef is involved in regulation of the interaction with calmodulin in vivo |
| GO:0005515 protein binding | IPI PMID:16760425 CP110 cooperates with two calcium-binding proteins to regula... | REMOVE | Summary: CP110 binding for cytokinesis - better captured by specific annotations. Reason: CP110 interaction already well-covered by centrosome localization and cytokinesis regulation annotations. Generic protein binding redundant. Supporting Evidence: PMID:16760425 CP110 cooperates with two calcium-binding proteins to regulate cytokinesis and genome stability |
| GO:0005515 protein binding | IPI PMID:21299499 IQ-motif selectivity in human IQGAP2 and IQGAP3: binding of ... | KEEP AS NON CORE | Summary: IQGAP binding for cytoskeletal regulation. Reason: IPI evidence (PMID:21299499) shows IQ-motif binding to IQGAP2/3. Important for cytoskeletal regulation but not core universal function. Supporting Evidence: PMID:21299499 IQ-motif selectivity in human IQGAP2 and IQGAP3: binding of calmodulin and myosin essential light chain |
| GO:0005515 protein binding | IPI PMID:3111527 Comparison of S100b protein with calmodulin: interactions wi... | KEEP AS NON CORE | Summary: Interaction with tau proteins and melittin. Reason: IPI evidence (PMID:3111527) shows interaction with tau proteins. Relevant for neurodegeneration but not core function. Supporting Evidence: PMID:3111527 Comparison of S100b protein with calmodulin: interactions with melittin and microtubule-associated tau proteins |
| GO:0005634 nucleus | HDA PMID:21630459 Proteomic characterization of the human sperm nucleus. | KEEP AS NON CORE | Summary: Sperm nuclear localization from proteomics. Reason: HDA evidence from sperm nucleus proteomics. Specialized reproductive cell localization, not core. Supporting Evidence: PMID:21630459 Proteomic characterization of the human sperm nucleus |
| GO:0005737 cytoplasm | TAS PMID:10899953 Calmodulin regulation of basal and agonist-stimulated G prot... | ACCEPT | Summary: Core cytoplasmic localization with TAS evidence. Reason: TAS evidence confirms primary cytoplasmic localization where CALM1 performs most functions. Supporting Evidence: PMID:10899953 Calmodulin regulation of basal and agonist-stimulated G protein coupling by the mu-opioid receptor |
| GO:0005813 centrosome | IDA PMID:16760425 CP110 cooperates with two calcium-binding proteins to regula... | ACCEPT | Summary: Direct experimental evidence for centrosomal localization. Reason: IDA evidence directly demonstrates centrosomal localization and functional importance for cytokinesis. Supporting Evidence: PMID:16760425 CP110 cooperates with two calcium-binding proteins to regulate cytokinesis and genome stability |
| GO:0005876 spindle microtubule | IDA PMID:16760425 CP110 cooperates with two calcium-binding proteins to regula... | ACCEPT | Summary: Direct evidence for spindle microtubule localization. Reason: IDA evidence confirms spindle microtubule localization essential for mitosis and cytokinesis. Supporting Evidence: PMID:16760425 depletion leads to a failure at a late stage of cytokinesis and the formation of binucleate cells |
| GO:0005886 plasma membrane | TAS PMID:10899953 Calmodulin regulation of basal and agonist-stimulated G prot... | ACCEPT | Summary: Plasma membrane localization for GPCR regulation. Reason: TAS evidence shows plasma membrane localization for G protein-coupled receptor regulation. Important for membrane-associated signaling. Supporting Evidence: PMID:10899953 Calmodulin regulation of basal and agonist-stimulated G protein coupling by the mu-opioid receptor |
| GO:0007186 G protein-coupled receptor signaling pathway | TAS PMID:10899953 Calmodulin regulation of basal and agonist-stimulated G prot... | ACCEPT | Summary: CALM1 regulates GPCR signaling, particularly opioid receptors. Reason: TAS evidence shows CALM1 regulation of mu-opioid receptor and GPCR signaling. Important signaling pathway regulation. Supporting Evidence: PMID:10899953 Calmodulin regulation of basal and agonist-stimulated G protein coupling by the mu-opioid receptor |
| GO:0021762 substantia nigra development | HEP PMID:22926577 Quantitative proteomic analysis of human substantia nigra in... | REMOVE | Summary: Expression in substantia nigra but not functionally validated for development. Reason: HEP (high-throughput expression pattern) evidence only shows CALM1 expression in substantia nigra from proteomic study. No functional validation for developmental role. Expression does not equal function. Supporting Evidence: PMID:22926577 Quantitative proteomic analysis of human substantia nigra in Alzheimer's disease, Huntington's disease and Multiple sclerosis |
| GO:0031982 vesicle | HDA PMID:19190083 Characterization of exosome-like vesicles released from huma... | KEEP AS NON CORE | Summary: Presence in exosome-like vesicles from epithelium. Reason: HDA evidence from exosome proteomics. Reflects vesicular trafficking role but not core function. Supporting Evidence: PMID:19190083 Characterization of exosome-like vesicles released from human tracheobronchial ciliated epithelium: a possible role in innate defense |
| GO:0032465 regulation of cytokinesis | IMP PMID:16760425 CP110 cooperates with two calcium-binding proteins to regula... | ACCEPT | Summary: Direct functional evidence for cytokinesis regulation. Reason: IMP evidence shows CALM1 depletion causes cytokinesis failure. Essential for proper cell division completion. Supporting Evidence: PMID:16760425 its depletion leads to a failure at a late stage of cytokinesis and the formation of binucleate cells, mirroring the defects resulting from ablation of either CaM or centrin function |
| GO:0005509 calcium ion binding | IDA PMID:11807546 Structural basis for the activation of anthrax adenylyl cycl... | ACCEPT | Summary: Duplicate calcium binding with anthrax toxin study evidence. Reason: Core function with IDA evidence from structural study with anthrax adenylyl cyclase. Supporting Evidence: PMID:11807546 Structural basis for the activation of anthrax adenylyl cyclase exotoxin by calmodulin |
| GO:0032991 protein-containing complex | IDA PMID:19855925 Structural analysis of the complex between calmodulin and fu... | ACCEPT | Summary: Calmodulin functions as a core component of various protein-containing complexes, including calcium-dependent kinase complexes and phosphatase complexes that are essential for calcium signaling. Reason: Protein-containing complex localization is fundamental to calmodulin's function as a calcium sensor that regulates multiple enzymes through direct protein-protein interactions in multiprotein complexes. Supporting Evidence: PMID:19855925 Structural analysis of the complex between calmodulin and full-length myelin basic protein |
| GO:1902494 catalytic complex | IDA PMID:11807546 Structural basis for the activation of anthrax adenylyl cycl... | ACCEPT | Summary: Calmodulin forms catalytic complexes with adenylate cyclases in calcium-dependent manner to regulate cAMP signaling. This represents a core regulatory mechanism for calcium-dependent activation of adenylate cyclase. Reason: Catalytic complex formation is central to calmodulin's function as an adenylate cyclase activator, enabling calcium-dependent regulation of cAMP production in G protein-coupled receptor signaling pathways. Supporting Evidence: PMID:11807546 Structural basis for the activation of anthrax adenylyl cyclase exotoxin by calmodulin |
| GO:0005576 extracellular region | TAS Reactome:R-HSA-482772 | KEEP AS NON CORE | Summary: Extracellular release from platelets. Reason: TAS from Reactome showing platelet release of cytosolic components. Specialized platelet function, not core. Supporting Evidence: Reactome:R-HSA-482772 Release of platelet cytosolic components |
| GO:0005654 nucleoplasm | TAS Reactome:R-HSA-111915 | ACCEPT | Summary: Nuclear localization for CAMK4 regulation. Reason: Nucleoplasm is a core localization for calmodulin (CALM1), which regulates nuclear proteins and transcription factors. This annotation is correct regardless of specific pathway context. Supporting Evidence: Reactome:R-HSA-111915 CAMK4 autophosphorylates |
| GO:0005654 nucleoplasm | TAS Reactome:R-HSA-2730867 | ACCEPT | Summary: Reactome pathway annotation - see individual pathways for specific functions Reason: TAS evidence from curated Reactome pathways. These annotations reflect the diverse cellular processes involving CALM1. |
| GO:0005654 nucleoplasm | TAS Reactome:R-HSA-442749 | ACCEPT | Summary: Reactome pathway annotation - see individual pathways for specific functions Reason: TAS evidence from curated Reactome pathways. These annotations reflect the diverse cellular processes involving CALM1. |
| GO:0005654 nucleoplasm | TAS Reactome:R-HSA-4551465 | ACCEPT | Summary: Reactome pathway annotation - see individual pathways for specific functions Reason: TAS evidence from curated Reactome pathways. These annotations reflect the diverse cellular processes involving CALM1. |
| GO:0005654 nucleoplasm | TAS Reactome:R-NUL-9618916 | ACCEPT | Summary: Reactome pathway annotation - see individual pathways for specific functions Reason: TAS evidence from curated Reactome pathways. These annotations reflect the diverse cellular processes involving CALM1. |
| GO:0005654 nucleoplasm | TAS Reactome:R-NUL-9619177 | ACCEPT | Summary: Reactome pathway annotation - see individual pathways for specific functions Reason: TAS evidence from curated Reactome pathways. These annotations reflect the diverse cellular processes involving CALM1. |
| GO:0005886 plasma membrane | TAS Reactome:R-HSA-202110 | ACCEPT | Summary: Reactome pathway annotation - see individual pathways for specific functions Reason: TAS evidence from curated Reactome pathways. These annotations reflect the diverse cellular processes involving CALM1. |
| GO:0005886 plasma membrane | TAS Reactome:R-HSA-202111 | ACCEPT | Summary: Reactome pathway annotation - see individual pathways for specific functions Reason: TAS evidence from curated Reactome pathways. These annotations reflect the diverse cellular processes involving CALM1. |
| GO:0005886 plasma membrane | TAS Reactome:R-HSA-202129 | ACCEPT | Summary: Reactome pathway annotation - see individual pathways for specific functions Reason: TAS evidence from curated Reactome pathways. These annotations reflect the diverse cellular processes involving CALM1. |
| GO:0005886 plasma membrane | TAS Reactome:R-HSA-202137 | ACCEPT | Summary: Reactome pathway annotation - see individual pathways for specific functions Reason: TAS evidence from curated Reactome pathways. These annotations reflect the diverse cellular processes involving CALM1. |
| GO:0005886 plasma membrane | TAS Reactome:R-HSA-202144 | ACCEPT | Summary: Reactome pathway annotation - see individual pathways for specific functions Reason: TAS evidence from curated Reactome pathways. These annotations reflect the diverse cellular processes involving CALM1. |
| GO:0005886 plasma membrane | TAS Reactome:R-HSA-5626549 | ACCEPT | Summary: Reactome pathway annotation for CALM1 in plasma membrane. Reason: Plasma membrane is a core localization for calmodulin (CALM1), which regulates numerous membrane-associated proteins and ion channels. This annotation is correct regardless of specific pathway context. Supporting Evidence: Reactome:R-HSA-2730867 Translocation of CaN:CaM:NFAT to nucleus |
| GO:0005829 cytosol | TAS Reactome:R-HSA-111966 | ACCEPT | Summary: Reactome pathway annotation - see individual pathways for specific functions Reason: TAS evidence from curated Reactome pathways. These annotations reflect the diverse cellular processes involving CALM1. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-1497784 | ACCEPT | Summary: Reactome pathway annotation - see individual pathways for specific functions Reason: TAS evidence from curated Reactome pathways. These annotations reflect the diverse cellular processes involving CALM1. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-1497796 | ACCEPT | Summary: Reactome pathway annotation - see individual pathways for specific functions Reason: TAS evidence from curated Reactome pathways. These annotations reflect the diverse cellular processes involving CALM1. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-1497810 | ACCEPT | Summary: Reactome pathway annotation - see individual pathways for specific functions Reason: TAS evidence from curated Reactome pathways. These annotations reflect the diverse cellular processes involving CALM1. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-1855153 | ACCEPT | Summary: Reactome pathway annotation - see individual pathways for specific functions Reason: TAS evidence from curated Reactome pathways. These annotations reflect the diverse cellular processes involving CALM1. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-202110 | ACCEPT | Summary: Reactome pathway annotation - see individual pathways for specific functions Reason: TAS evidence from curated Reactome pathways. These annotations reflect the diverse cellular processes involving CALM1. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-202111 | ACCEPT | Summary: Reactome pathway annotation - see individual pathways for specific functions Reason: TAS evidence from curated Reactome pathways. These annotations reflect the diverse cellular processes involving CALM1. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-202127 | ACCEPT | Summary: Reactome pathway annotation - see individual pathways for specific functions Reason: TAS evidence from curated Reactome pathways. These annotations reflect the diverse cellular processes involving CALM1. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-202129 | ACCEPT | Summary: Reactome pathway annotation - see individual pathways for specific functions Reason: TAS evidence from curated Reactome pathways. These annotations reflect the diverse cellular processes involving CALM1. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-2025890 | ACCEPT | Summary: Reactome pathway annotation - see individual pathways for specific functions Reason: TAS evidence from curated Reactome pathways. These annotations reflect the diverse cellular processes involving CALM1. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-2730849 | ACCEPT | Summary: Reactome pathway annotation - see individual pathways for specific functions Reason: TAS evidence from curated Reactome pathways. These annotations reflect the diverse cellular processes involving CALM1. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-2730867 | ACCEPT | Summary: Reactome pathway annotation - see individual pathways for specific functions Reason: TAS evidence from curated Reactome pathways. These annotations reflect the diverse cellular processes involving CALM1. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-2730872 | ACCEPT | Summary: Reactome pathway annotation - see individual pathways for specific functions Reason: TAS evidence from curated Reactome pathways. These annotations reflect the diverse cellular processes involving CALM1. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-3229181 | ACCEPT | Summary: Reactome pathway annotation - see individual pathways for specific functions Reason: TAS evidence from curated Reactome pathways. These annotations reflect the diverse cellular processes involving CALM1. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-4332358 | ACCEPT | Summary: Reactome pathway annotation - see individual pathways for specific functions Reason: TAS evidence from curated Reactome pathways. These annotations reflect the diverse cellular processes involving CALM1. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-4332359 | ACCEPT | Summary: Reactome pathway annotation - see individual pathways for specific functions Reason: TAS evidence from curated Reactome pathways. These annotations reflect the diverse cellular processes involving CALM1. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-4332363 | ACCEPT | Summary: Reactome pathway annotation - see individual pathways for specific functions Reason: TAS evidence from curated Reactome pathways. These annotations reflect the diverse cellular processes involving CALM1. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-445797 | ACCEPT | Summary: Reactome pathway annotation - see individual pathways for specific functions Reason: TAS evidence from curated Reactome pathways. These annotations reflect the diverse cellular processes involving CALM1. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-445813 | ACCEPT | Summary: Reactome pathway annotation - see individual pathways for specific functions Reason: TAS evidence from curated Reactome pathways. These annotations reflect the diverse cellular processes involving CALM1. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-451283 | ACCEPT | Summary: Reactome pathway annotation - see individual pathways for specific functions Reason: TAS evidence from curated Reactome pathways. These annotations reflect the diverse cellular processes involving CALM1. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-451311 | ACCEPT | Summary: Reactome pathway annotation - see individual pathways for specific functions Reason: TAS evidence from curated Reactome pathways. These annotations reflect the diverse cellular processes involving CALM1. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-4551451 | ACCEPT | Summary: Reactome pathway annotation - see individual pathways for specific functions Reason: TAS evidence from curated Reactome pathways. These annotations reflect the diverse cellular processes involving CALM1. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-4551465 | ACCEPT | Summary: Reactome pathway annotation - see individual pathways for specific functions Reason: TAS evidence from curated Reactome pathways. These annotations reflect the diverse cellular processes involving CALM1. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-482772 | ACCEPT | Summary: Reactome pathway annotation - see individual pathways for specific functions Reason: TAS evidence from curated Reactome pathways. These annotations reflect the diverse cellular processes involving CALM1. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-5672965 | ACCEPT | Summary: Reactome pathway annotation - see individual pathways for specific functions Reason: TAS evidence from curated Reactome pathways. These annotations reflect the diverse cellular processes involving CALM1. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-71541 | ACCEPT | Summary: Reactome pathway annotation - see individual pathways for specific functions Reason: TAS evidence from curated Reactome pathways. These annotations reflect the diverse cellular processes involving CALM1. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-71588 | ACCEPT | Summary: Reactome pathway annotation - see individual pathways for specific functions Reason: TAS evidence from curated Reactome pathways. These annotations reflect the diverse cellular processes involving CALM1. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-9618785 | ACCEPT | Summary: Reactome pathway annotation - see individual pathways for specific functions Reason: TAS evidence from curated Reactome pathways. These annotations reflect the diverse cellular processes involving CALM1. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-9619355 | ACCEPT | Summary: Reactome pathway annotation - see individual pathways for specific functions Reason: TAS evidence from curated Reactome pathways. These annotations reflect the diverse cellular processes involving CALM1. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-9619376 | ACCEPT | Summary: Reactome pathway annotation - see individual pathways for specific functions Reason: TAS evidence from curated Reactome pathways. These annotations reflect the diverse cellular processes involving CALM1. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-9653585 | ACCEPT | Summary: Reactome pathway annotation - see individual pathways for specific functions Reason: TAS evidence from curated Reactome pathways. These annotations reflect the diverse cellular processes involving CALM1. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-9654521 | ACCEPT | Summary: Reactome pathway annotation - see individual pathways for specific functions Reason: TAS evidence from curated Reactome pathways. These annotations reflect the diverse cellular processes involving CALM1. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-9654523 | ACCEPT | Summary: Reactome pathway annotation - see individual pathways for specific functions Reason: TAS evidence from curated Reactome pathways. These annotations reflect the diverse cellular processes involving CALM1. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-9654525 | ACCEPT | Summary: Reactome pathway annotation - see individual pathways for specific functions Reason: TAS evidence from curated Reactome pathways. These annotations reflect the diverse cellular processes involving CALM1. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-9654533 | ACCEPT | Summary: Reactome pathway annotation - see individual pathways for specific functions Reason: TAS evidence from curated Reactome pathways. These annotations reflect the diverse cellular processes involving CALM1. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-9865670 | ACCEPT | Summary: Reactome pathway annotation - see individual pathways for specific functions Reason: TAS evidence from curated Reactome pathways. These annotations reflect the diverse cellular processes involving CALM1. |
| GO:0005829 cytosol | TAS Reactome:R-NUL-9617449 | ACCEPT | Summary: Reactome pathway annotation - see individual pathways for specific functions Reason: TAS evidence from curated Reactome pathways. These annotations reflect the diverse cellular processes involving CALM1. |
| GO:0005829 cytosol | TAS Reactome:R-NUL-9619243 | ACCEPT | Summary: Reactome pathway annotation - see individual pathways for specific functions Reason: TAS evidence from curated Reactome pathways. These annotations reflect the diverse cellular processes involving CALM1. |
| GO:0005829 cytosol | TAS Reactome:R-NUL-9619396 | ACCEPT | Summary: Reactome pathway annotation - see individual pathways for specific functions Reason: TAS evidence from curated Reactome pathways. These annotations reflect the diverse cellular processes involving CALM1. |
| GO:0005829 cytosol | TAS Reactome:R-NUL-9619413 | ACCEPT | Summary: Reactome pathway annotation - see individual pathways for specific functions Reason: TAS evidence from curated Reactome pathways. These annotations reflect the diverse cellular processes involving CALM1. |
| GO:0002027 regulation of heart rate | IMP PMID:23040497 Mutations in calmodulin cause ventricular tachycardia and su... | ACCEPT | Summary: Duplicate with IMP evidence for core cardiac function. Reason: IMP evidence from calmodulinopathy study directly demonstrates role in heart rate regulation. CALM1 mutations cause arrhythmias. Supporting Evidence: PMID:23040497 Mutations in calmodulin cause ventricular tachycardia and sudden cardiac death |
| GO:0005509 calcium ion binding | IDA PMID:23040497 Mutations in calmodulin cause ventricular tachycardia and su... | ACCEPT | Summary: Another duplicate with IDA evidence from calmodulinopathy study. Reason: Core function with direct experimental evidence from disease mutation study. 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: Duplicate with IDA evidence from titin kinase study. Reason: Core function demonstrated in cardiac titin kinase binding study. Supporting Evidence: PMID:7607248 A calmodulin-binding sequence in the C-terminus of human cardiac titin kinase |
| GO:0005509 calcium ion binding | IDA PMID:8631777 Blocking the Ca2+-induced conformational transitions in calm... | ACCEPT | Summary: Duplicate with IDA evidence from calmodulin conformational study. Reason: Core function with biochemical evidence on calcium-induced conformational changes. Supporting Evidence: PMID:8631777 Blocking the Ca2+-induced conformational transitions in calmodulin with disulfide bonds |
| GO:0005513 detection of calcium ion | IMP PMID:23040497 Mutations in calmodulin cause ventricular tachycardia and su... | ACCEPT | Summary: Core calcium sensing with IMP evidence from disease study. Reason: Functional evidence shows CALM1 mutations impair calcium sensing causing cardiac disease. Supporting Evidence: PMID:23040497 Both CALM1 substitutions demonstrated compromised calcium binding, and p.Asn97Ser displayed an aberrant interaction with the RYR2 calmodulin-binding-domain peptide at low calcium concentrations |
| 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: Reactome pathway annotation - see individual pathways for specific functions Reason: TAS evidence from curated Reactome pathways. These annotations reflect the diverse cellular processes involving CALM1. Supporting Evidence: PMID:20226167 Defective calmodulin binding to the cardiac ryanodine receptor plays a key role in CPVT-associated channel dysfunction. |
| GO:0019901 protein kinase binding | IPI PMID:20668654 Structure of the CaMKIIdelta/calmodulin complex reveals the ... | ACCEPT | Summary: Reactome pathway annotation - see individual pathways for specific functions Reason: TAS evidence from curated Reactome pathways. These annotations reflect the diverse cellular processes involving CALM1. Supporting Evidence: PMID:20668654 Structure of the CaMKIIdelta/calmodulin complex reveals the molecular mechanism of CaMKII kinase activation. |
| GO:0030017 sarcomere | IDA PMID:20226167 Defective calmodulin binding to the cardiac ryanodine recept... | ACCEPT | Summary: Reactome pathway annotation - see individual pathways for specific functions Reason: TAS evidence from curated Reactome pathways. These annotations reflect the diverse cellular processes involving CALM1. Supporting Evidence: PMID:20226167 Defective calmodulin binding to the cardiac ryanodine receptor plays a key role in CPVT-associated channel dysfunction. |
| GO:0031432 titin binding | IPI PMID:7607248 A calmodulin-binding sequence in the C-terminus of human car... | ACCEPT | Summary: Reactome pathway annotation - see individual pathways for specific functions Reason: TAS evidence from curated Reactome pathways. These annotations reflect the diverse cellular processes involving CALM1. Supporting Evidence: PMID:7607248 A calmodulin-binding sequence in the C-terminus of human cardiac titin kinase. |
| GO:0043539 protein serine/threonine kinase activator activity | TAS PMID:20668654 Structure of the CaMKIIdelta/calmodulin complex reveals the ... | ACCEPT | Summary: Reactome pathway annotation - see individual pathways for specific functions Reason: TAS evidence from curated Reactome pathways. These annotations reflect the diverse cellular processes involving CALM1. Supporting Evidence: PMID:20668654 Structure of the CaMKIIdelta/calmodulin complex reveals the molecular mechanism of CaMKII kinase activation. |
| GO:0044325 transmembrane transporter binding | IPI PMID:21167176 Solution NMR structure of Apo-calmodulin in complex with the... | ACCEPT | Summary: CALM1 binds IQ motif of cardiac sodium channel NaV1.5 for regulation. Reason: IPI evidence (PMID:21167176) demonstrates specific binding to sodium channel NaV1.5 IQ motif. Important for cardiac ion channel regulation beyond just calcium channels. Supporting Evidence: PMID:21167176 Solution NMR structure of Apo-calmodulin in complex with the IQ motif of human cardiac sodium channel NaV1.5 |
| GO:0044325 transmembrane transporter binding | IPI PMID:23040497 Mutations in calmodulin cause ventricular tachycardia and su... | ACCEPT | Summary: Reactome pathway annotation - see individual pathways for specific functions Reason: TAS evidence from curated Reactome pathways. These annotations reflect the diverse cellular processes involving CALM1. Supporting Evidence: PMID:23040497 Mutations in calmodulin cause ventricular tachycardia and sudden cardiac death. |
| GO:0051592 response to calcium ion | IDA PMID:7607248 A calmodulin-binding sequence in the C-terminus of human car... | ACCEPT | Summary: CALM1 responds to calcium through conformational change and target binding. Reason: IDA evidence shows calcium-dependent response through titin kinase binding. Core mechanism of CALM1 function. Supporting Evidence: PMID:7607248 A calmodulin-binding sequence in the C-terminus of human cardiac titin kinase |
| GO:0055117 regulation of cardiac muscle contraction | IMP PMID:23040497 Mutations in calmodulin cause ventricular tachycardia and su... | ACCEPT | Summary: Reactome pathway annotation - see individual pathways for specific functions Reason: TAS evidence from curated Reactome pathways. These annotations reflect the diverse cellular processes involving CALM1. Supporting Evidence: PMID:23040497 Mutations in calmodulin cause ventricular tachycardia and sudden cardiac death. |
| GO:0072542 protein phosphatase activator activity | IDA PMID:8631777 Blocking the Ca2+-induced conformational transitions in calm... | ACCEPT | Summary: Reactome pathway annotation - see individual pathways for specific functions Reason: TAS evidence from curated Reactome pathways. These annotations reflect the diverse cellular processes involving CALM1. Supporting Evidence: PMID:8631777 Blocking the Ca2+-induced conformational transitions in calmodulin with disulfide bonds. |
| GO:0005509 calcium ion binding | IDA PMID:26164367 Distinctive malfunctions of calmodulin mutations associated ... | ACCEPT | Summary: Duplicate with IDA evidence from RyR2 arrhythmia study. Reason: Core function studied in context of calmodulin mutations and RyR2-mediated disease. Supporting Evidence: PMID:26164367 Distinctive malfunctions of calmodulin mutations associated with heart RyR2-mediated arrhythmic disease |
| GO:0005509 calcium ion binding | IDA PMID:26969752 Spectrum and Prevalence of CALM1-, CALM2-, and CALM3-Encoded... | ACCEPT | Summary: Duplicate with IDA evidence from LQTS study. Reason: Core function studied in Long QT syndrome mutations. Supporting Evidence: PMID:26969752 Spectrum and Prevalence of CALM1-, CALM2-, and CALM3-Encoded Calmodulin Variants in Long QT Syndrome |
| GO:0005509 calcium ion binding | IDA PMID:27516456 Novel CPVT-Associated Calmodulin Mutation in CALM3 (CALM3-A1... | ACCEPT | Summary: Duplicate with IDA evidence from CPVT mutation study. Reason: Core function studied in CPVT-associated CALM3-A103V mutation. Supporting Evidence: PMID:27516456 Novel CPVT-Associated Calmodulin Mutation in CALM3 (CALM3-A103V) Activates Arrhythmogenic Ca Waves and Sparks |
| GO:0005737 cytoplasm | IDA PMID:27165696 Arrhythmogenic calmodulin mutations impede activation of sma... | ACCEPT | Summary: Reactome pathway annotation - see individual pathways for specific functions Reason: TAS evidence from curated Reactome pathways. These annotations reflect the diverse cellular processes involving CALM1. Supporting Evidence: PMID:27165696 2016 May 7. Arrhythmogenic calmodulin mutations impede activation of small-conductance calcium-activated potassium current. |
| GO:0019855 calcium channel inhibitor activity | IDA PMID:26969752 Spectrum and Prevalence of CALM1-, CALM2-, and CALM3-Encoded... | ACCEPT | Summary: CALM1 inhibits calcium channels - mutations cause Long QT syndrome through loss of inhibition. Reason: IDA evidence (PMID:26969752) from LQTS study shows CALM1 inhibits calcium channels. E141G mutation impairs this function causing LQTS. Important negative regulatory function. Supporting Evidence: PMID:26969752 Spectrum and Prevalence of CALM1-, CALM2-, and CALM3-Encoded Calmodulin Variants in Long QT Syndrome and Functional Characterization of a Novel Long QT Syndrome-Associated Calmodulin Missense Variant, E141G |
| GO:0060314 regulation of ryanodine-sensitive calcium-release channel activity | IDA PMID:22067155 FRET detection of calmodulin binding to the cardiac RyR2 cal... | ACCEPT | Summary: Reactome pathway annotation - see individual pathways for specific functions Reason: TAS evidence from curated Reactome pathways. These annotations reflect the diverse cellular processes involving CALM1. Supporting Evidence: PMID:22067155 Nov 1. FRET detection of calmodulin binding to the cardiac RyR2 calcium release channel. |
| GO:0060315 negative regulation of ryanodine-sensitive calcium-release channel activity | IDA PMID:26164367 Distinctive malfunctions of calmodulin mutations associated ... | ACCEPT | Summary: Core cardiac function - CALM1 negatively regulates RyR2 to prevent calcium leak and arrhythmias. Reason: IDA evidence (PMID:26164367) shows CALM1 inhibits RyR2 activity. Disease mutations impair this inhibition causing CPVT through excessive calcium release. Essential for cardiac calcium homeostasis. Supporting Evidence: PMID:26164367 Distinctive malfunctions of calmodulin mutations associated with heart RyR2-mediated arrhythmic disease |
| GO:0005515 protein binding | IPI PMID:16127172 Calcium/calmodulin regulates ubiquitination of the ubiquitin... | ACCEPT | Summary: Reactome pathway annotation - see individual pathways for specific functions Reason: TAS evidence from curated Reactome pathways. These annotations reflect the diverse cellular processes involving CALM1. Supporting Evidence: PMID:16127172 2005 Aug 26. Calcium/calmodulin regulates ubiquitination of the ubiquitin-specific protease TRE17/USP6. |
| GO:0005509 calcium ion binding | IDA PMID:27564677 Structural Insights into the M-Channel Proximal C-Terminus/C... | ACCEPT | Summary: Duplicate with IDA evidence from M-channel/KCNQ study. Reason: Core function demonstrated in structural study of KCNQ channel regulation. Supporting Evidence: PMID:27564677 Structural Insights into the M-Channel Proximal C-Terminus/Calmodulin Complex |
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