id: P0DP23
gene_symbol: CALM1
taxon:
  id: NCBITaxon:9606
  label: Homo sapiens
description: 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.
existing_annotations:
- term:
    id: GO:0005509
    label: calcium ion binding
  evidence_type: IBA
  original_reference_id: GO_REF:0000033
  review:
    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.
    action: ACCEPT
    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.
    supported_by:
    - reference_id: PMID:23040497
      supporting_text: Both CALM1 substitutions demonstrated compromised calcium binding
    - reference_id: file:human/CALM1/CALM1-deep-research-falcon.md
      supporting_text: See deep research file for comprehensive analysis
    - reference_id: file:human/CALM1/CALM1-falcon-research.md
      supporting_text: See deep research file for comprehensive analysis
- term:
    id: GO:0005634
    label: nucleus
  evidence_type: IBA
  original_reference_id: GO_REF:0000033
  review:
    summary: Nuclear localization supported by high-throughput proteomic study but
      not core function.
    action: KEEP_AS_NON_CORE
    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.
    supported_by:
    - reference_id: PMID:21630459
      supporting_text: Proteomic characterization of the human sperm nucleus
- term:
    id: GO:0010880
    label: regulation of release of sequestered calcium ion into cytosol by sarcoplasmic
      reticulum
  evidence_type: IBA
  original_reference_id: GO_REF:0000033
  review:
    summary: Core cardiac function regulating calcium release from sarcoplasmic reticulum
      via RyR2 interaction.
    action: ACCEPT
    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.
    supported_by:
    - reference_id: PMID:20226167
      supporting_text: 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
- term:
    id: GO:0005513
    label: detection of calcium ion
  evidence_type: IBA
  original_reference_id: GO_REF:0000033
  review:
    summary: Core calcium sensing function - undergoes conformational change upon
      calcium binding to activate downstream targets.
    action: ACCEPT
    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).
    supported_by:
    - reference_id: PMID:23040497
      supporting_text: Mutations in calmodulin cause ventricular tachycardia and sudden
        cardiac death...Both CALM1 substitutions demonstrated compromised calcium
        binding
- term:
    id: GO:0097720
    label: calcineurin-mediated signaling
  evidence_type: IBA
  original_reference_id: GO_REF:0000033
  review:
    summary: Core signaling function - CALM1 binds and activates calcineurin phosphatase
      in calcium-dependent manner.
    action: ACCEPT
    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.
    supported_by:
    - reference_id: PMID:8631777
      supporting_text: Blocking the Ca2+-induced conformational transitions in calmodulin
        with disulfide bonds
- term:
    id: GO:0005737
    label: cytoplasm
  evidence_type: IBA
  original_reference_id: GO_REF:0000033
  review:
    summary: Core cytoplasmic localization where CALM1 performs most calcium-sensing
      and signaling functions.
    action: ACCEPT
    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.
    supported_by:
    - reference_id: PMID:27165696
      supporting_text: Arrhythmogenic calmodulin mutations impede activation of small-conductance
        calcium-activated potassium current
    - reference_id: PMID:10899953
      supporting_text: Calmodulin regulation of basal and agonist-stimulated G protein
        coupling
- term:
    id: GO:0005813
    label: centrosome
  evidence_type: IBA
  original_reference_id: GO_REF:0000033
  review:
    summary: Important centrosomal localization for cell division regulation through
      interaction with CP110.
    action: ACCEPT
    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.
    supported_by:
    - reference_id: PMID:16760425
      supporting_text: CP110 interacts with two different Ca2+-binding proteins, calmodulin
        (CaM) and centrin, in vivo
- term:
    id: GO:0043209
    label: myelin sheath
  evidence_type: IBA
  original_reference_id: GO_REF:0000033
  review:
    summary: Myelin sheath localization likely related to interaction with myelin
      basic protein.
    action: KEEP_AS_NON_CORE
    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.
    supported_by:
    - reference_id: PMID:19855925
      supporting_text: Structural analysis of the complex between calmodulin and full-length
        myelin basic protein, an intrinsically disordered molecule
- term:
    id: GO:0000922
    label: spindle pole
  evidence_type: IEA
  original_reference_id: GO_REF:0000120
  review:
    summary: Spindle pole localization supported by experimental evidence for cell
      division regulation.
    action: ACCEPT
    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.
    supported_by:
    - reference_id: PMID:16760425
      supporting_text: CP110 cooperates with two calcium-binding proteins to regulate
        cytokinesis and genome stability
- term:
    id: GO:0002027
    label: regulation of heart rate
  evidence_type: IEA
  original_reference_id: GO_REF:0000117
  review:
    summary: Core cardiac function - CALM1 mutations cause arrhythmias demonstrating
      essential role in heart rate regulation.
    action: ACCEPT
    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.
    supported_by:
    - reference_id: PMID:23040497
      supporting_text: Mutations in calmodulin cause ventricular tachycardia and sudden
        cardiac death
- term:
    id: GO:0005246
    label: calcium channel regulator activity
  evidence_type: IEA
  original_reference_id: GO_REF:0000117
  review:
    summary: Core function - CALM1 regulates multiple calcium channels including L-type
      and ryanodine receptors.
    action: ACCEPT
    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).
    supported_by:
    - reference_id: PMID:20226167
      supporting_text: Defective calmodulin binding to the cardiac ryanodine receptor
        plays a key role in CPVT-associated channel dysfunction
    - reference_id: PMID:26969752
      supporting_text: alter the properties of the cardiac L-type calcium channel
- term:
    id: GO:0005509
    label: calcium ion binding
  evidence_type: IEA
  original_reference_id: GO_REF:0000120
  review:
    summary: Duplicate annotation with different evidence code - core function.
    action: ACCEPT
    reason: Same core calcium binding function as IBA annotation but from combined
      automated methods. Redundant but correct.
    supported_by:
    - reference_id: GO_REF:0000120
      supporting_text: Combined Automated Annotation using Multiple IEA Methods
- term:
    id: GO:0005513
    label: detection of calcium ion
  evidence_type: IEA
  original_reference_id: GO_REF:0000117
  review:
    summary: Duplicate of IBA annotation - core calcium sensing function.
    action: ACCEPT
    reason: Same essential calcium sensing function as IBA annotation but from ARBA
      machine learning. Redundant but correct.
    supported_by:
    - reference_id: GO_REF:0000117
      supporting_text: Electronic Gene Ontology annotations created by ARBA machine
        learning models
- term:
    id: GO:0005813
    label: centrosome
  evidence_type: IEA
  original_reference_id: GO_REF:0000120
  review:
    summary: Duplicate centrosome annotation - already covered by IBA.
    action: ACCEPT
    reason: Same centrosomal localization as IBA annotation. Supported by IDA evidence
      (PMID:16760425).
    supported_by:
    - reference_id: PMID:16760425
      supporting_text: CP110 cooperates with two calcium-binding proteins to regulate
        cytokinesis and genome stability
- term:
    id: GO:0005819
    label: spindle
  evidence_type: IEA
  original_reference_id: GO_REF:0000044
  review:
    summary: Spindle localization for cell division regulation.
    action: ACCEPT
    reason: Consistent with spindle pole and spindle microtubule localizations. CALM1
      regulates mitotic progression and cytokinesis at spindle.
    supported_by:
    - reference_id: GO_REF:0000044
      supporting_text: Gene Ontology annotation based on UniProtKB/Swiss-Prot Subcellular
        Location vocabulary mapping
- term:
    id: GO:0005876
    label: spindle microtubule
  evidence_type: IEA
  original_reference_id: GO_REF:0000117
  review:
    summary: Spindle microtubule localization for mitosis regulation.
    action: ACCEPT
    reason: IDA evidence (PMID:16760425) confirms spindle microtubule localization.
      CALM1 with CP110 regulates spindle function and cytokinesis.
    supported_by:
    - reference_id: PMID:16760425
      supporting_text: CP110 cooperates with two calcium-binding proteins to regulate
        cytokinesis and genome stability
- term:
    id: GO:0010856
    label: adenylate cyclase activator activity
  evidence_type: IEA
  original_reference_id: GO_REF:0000117
  review:
    summary: CALM1 activates adenylate cyclase, particularly bacterial adenylyl cyclase
      exotoxin.
    action: ACCEPT
    reason: IDA evidence (PMID:11807546) demonstrates direct activation of adenylyl
      cyclase by calmodulin. Important for cAMP signaling and exploited by bacterial
      pathogens like anthrax.
    supported_by:
    - reference_id: PMID:11807546
      supporting_text: Structural basis for the activation of anthrax adenylyl cyclase
        exotoxin by calmodulin
- term:
    id: GO:0010881
    label: regulation of cardiac muscle contraction by regulation of the release of
      sequestered calcium ion
  evidence_type: IEA
  original_reference_id: GO_REF:0000117
  review:
    summary: Core cardiac function regulating calcium-induced calcium release in cardiac
      muscle.
    action: ACCEPT
    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.
    supported_by:
    - reference_id: PMID:23040497
      supporting_text: Mutations in calmodulin cause ventricular tachycardia and sudden
        cardiac death
    - reference_id: PMID:20226167
      supporting_text: Defective calmodulin binding to the cardiac ryanodine receptor
        plays a key role in CPVT-associated channel dysfunction
- term:
    id: GO:0019901
    label: protein kinase binding
  evidence_type: IEA
  original_reference_id: GO_REF:0000117
  review:
    summary: Core function - CALM1 binds and regulates multiple protein kinases including
      CaMKII.
    action: ACCEPT
    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.
    supported_by:
    - reference_id: PMID:20668654
      supporting_text: Structure of the CaMKIIdelta/calmodulin complex reveals the
        molecular mechanism of CaMKII kinase activation
- term:
    id: GO:0030017
    label: sarcomere
  evidence_type: IEA
  original_reference_id: GO_REF:0000117
  review:
    summary: Sarcomere localization for muscle contraction regulation.
    action: ACCEPT
    reason: IDA evidence (PMID:20226167) demonstrates sarcomeric localization. CALM1
      regulates muscle contraction through RyR2 and titin interactions at sarcomere.
    supported_by:
    - reference_id: PMID:20226167
      supporting_text: Defective calmodulin binding to the cardiac ryanodine receptor
        plays a key role in CPVT-associated channel dysfunction
- term:
    id: GO:0031432
    label: titin binding
  evidence_type: IEA
  original_reference_id: GO_REF:0000117
  review:
    summary: CALM1 binds titin kinase domain in cardiac muscle for mechanosensing.
    action: ACCEPT
    reason: IPI evidence (PMID:7607248) demonstrates direct calmodulin binding to
      cardiac titin kinase C-terminus. Important for cardiac mechanosensing and muscle
      regulation.
    supported_by:
    - reference_id: PMID:7607248
      supporting_text: A calmodulin-binding sequence in the C-terminus of human cardiac
        titin kinase
- term:
    id: GO:0031514
    label: motile cilium
  evidence_type: IEA
  original_reference_id: GO_REF:0000044
  review:
    summary: Ciliary localization based on subcellular location mapping.
    action: KEEP_AS_NON_CORE
    reason: Based on UniProt subcellular location vocabulary mapping. CALM1 may regulate
      ciliary beating through calcium signaling but this is specialized, not core
      function.
    supported_by:
    - reference_id: GO_REF:0000044
      supporting_text: Gene Ontology annotation based on UniProtKB/Swiss-Prot Subcellular
        Location vocabulary mapping
- term:
    id: GO:0032465
    label: regulation of cytokinesis
  evidence_type: IEA
  original_reference_id: GO_REF:0000117
  review:
    summary: Important cell division function through CP110 interaction at centrosomes.
    action: ACCEPT
    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.
    supported_by:
    - reference_id: PMID:16760425
      supporting_text: 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
- term:
    id: GO:0034704
    label: calcium channel complex
  evidence_type: IEA
  original_reference_id: GO_REF:0000117
  review:
    summary: CALM1 associates with calcium channel complexes for regulation.
    action: ACCEPT
    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.
    supported_by:
    - reference_id: PMID:23040497
      supporting_text: Mutations in calmodulin cause ventricular tachycardia and sudden
        cardiac death
- term:
    id: GO:0043539
    label: protein serine/threonine kinase activator activity
  evidence_type: IEA
  original_reference_id: GO_REF:0000117
  review:
    summary: Core function - CALM1 activates multiple serine/threonine kinases including
      CaMKII in calcium-dependent manner.
    action: ACCEPT
    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.
    supported_by:
    - reference_id: PMID:35568036
      supporting_text: A family of conserved bacterial virulence factors dampens interferon
        responses by blocking calcium signaling
    - reference_id: PMID:14722083
      supporting_text: Comparative analyses of the three-dimensional structures and
        enzymatic properties of alpha, beta, gamma and delta isoforms of Ca2+-calmodulin-dependent
        protein kinase II
- term:
    id: GO:0046872
    label: metal ion binding
  evidence_type: IEA
  original_reference_id: GO_REF:0000043
  review:
    summary: Too general - calcium ion binding is the specific function.
    action: MODIFY
    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_replacement_terms:
    - id: GO:0005509
      label: calcium ion binding
    supported_by:
    - reference_id: GO_REF:0000043
      supporting_text: Gene Ontology annotation based on UniProtKB/Swiss-Prot keyword
        mapping
- term:
    id: GO:0060291
    label: long-term synaptic potentiation
  evidence_type: IEA
  original_reference_id: GO_REF:0000117
  review:
    summary: Important neuronal function through CaMKII activation in synaptic plasticity.
    action: KEEP_AS_NON_CORE
    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.
    supported_by:
    - reference_id: PMID:20668654
      supporting_text: Structure of the CaMKIIdelta/calmodulin complex reveals the
        molecular mechanism of CaMKII kinase activation
- term:
    id: GO:0072542
    label: protein phosphatase activator activity
  evidence_type: IEA
  original_reference_id: GO_REF:0000117
  review:
    summary: Core function - CALM1 activates calcineurin phosphatase in calcium-dependent
      manner.
    action: ACCEPT
    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.
    supported_by:
    - reference_id: PMID:8631777
      supporting_text: Blocking the Ca2+-induced conformational transitions in calmodulin
        with disulfide bonds
- term:
    id: GO:0097720
    label: calcineurin-mediated signaling
  evidence_type: IEA
  original_reference_id: GO_REF:0000117
  review:
    summary: Duplicate of IBA annotation - core signaling function.
    action: ACCEPT
    reason: Same calcineurin signaling function as IBA annotation. IDA evidence (PMID:8631777)
      supports this.
    supported_by:
    - reference_id: PMID:8631777
      supporting_text: Blocking the Ca2+-induced conformational transitions in calmodulin
        with disulfide bonds
- term:
    id: GO:1901844
    label: regulation of cell communication by electrical coupling involved in cardiac
      conduction
  evidence_type: IEA
  original_reference_id: GO_REF:0000117
  review:
    summary: Core cardiac conduction function - CALM1 mutations disrupt electrical
      coupling causing arrhythmias.
    action: ACCEPT
    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.
    supported_by:
    - reference_id: PMID:23040497
      supporting_text: Mutations in calmodulin cause ventricular tachycardia and sudden
        cardiac death...characterized by episodic syncope and/or sudden cardiac arrest
        during exercise or acute emotion
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:30842726
  review:
    summary: Generic protein binding annotation for IQSEC2 interaction, lacks specificity.
    action: MODIFY
    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_replacement_terms:
    - id: GO:0008047
      label: enzyme activator activity
    - id: GO:0030276
      label: clathrin binding
    supported_by:
    - reference_id: PMID:30842726
      supporting_text: An IQSEC2 Mutation Associated With Intellectual Disability
        and Autism Results in Decreased Surface AMPA Receptors
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:31983428
  review:
    summary: Generic protein binding for IDH1 interaction, lacks functional specificity.
    action: MODIFY
    reason: Interaction with IDH1 is documented (PMID:31983428) but generic protein
      binding term uninformative. Need more specific functional annotation.
    proposed_replacement_terms:
    - id: GO:0008047
      label: enzyme activator activity
    supported_by:
    - reference_id: PMID:31983428
      supporting_text: Interaction between IDH1 WT and calmodulin and its implications
        for glioblastoma cell growth and migration
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:35271311
  review:
    summary: Generic protein binding from OpenCell proteomics study.
    action: REMOVE
    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.
    supported_by:
    - reference_id: PMID:35271311
      supporting_text: 'OpenCell: Endogenous tagging for the cartography of human
        cellular organization'
- term:
    id: GO:0000086
    label: G2/M transition of mitotic cell cycle
  evidence_type: IEA
  original_reference_id: GO_REF:0000120
  review:
    summary: CALM1 regulates G2/M transition through centrosome/spindle functions.
    action: ACCEPT
    reason: Consistent with demonstrated role in cytokinesis and spindle regulation
      through CP110 interaction (PMID:16760425). CALM1 required for proper mitotic
      progression.
    supported_by:
    - reference_id: PMID:16760425
      supporting_text: CP110 cooperates with two calcium-binding proteins to regulate
        cytokinesis and genome stability
- term:
    id: GO:0008076
    label: voltage-gated potassium channel complex
  evidence_type: IEA
  original_reference_id: GO_REF:0000120
  review:
    summary: CALM1 regulates voltage-gated potassium channels like KCNQ.
    action: ACCEPT
    reason: Well-documented interaction with KCNQ channels. PMID:27564677 shows CALM1
      binding to KCNQ/M-channels. Important for neuronal excitability and cardiac
      repolarization.
    supported_by:
    - reference_id: PMID:27564677
      supporting_text: Structural Insights into the M-Channel Proximal C-Terminus/Calmodulin
        Complex
- term:
    id: GO:0016020
    label: membrane
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  review:
    summary: Too general - specific membrane systems are better annotated.
    action: REMOVE
    reason: Generic membrane annotation adds no value beyond specific membrane localizations
      already annotated (plasma membrane, ER contacts, etc.). Based on ortholog transfer.
    supported_by:
    - reference_id: GO_REF:0000107
      supporting_text: Automatic transfer of experimentally verified manual GO annotation
        data to orthologs
- term:
    id: GO:0031982
    label: vesicle
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  review:
    summary: General vesicle localization supported by exosome study.
    action: KEEP_AS_NON_CORE
    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.
    supported_by:
    - reference_id: PMID:19190083
      supporting_text: 'Characterization of exosome-like vesicles released from human
        tracheobronchial ciliated epithelium: a possible role in innate defense'
- term:
    id: GO:0043209
    label: myelin sheath
  evidence_type: IEA
  original_reference_id: GO_REF:0000120
  review:
    summary: Duplicate myelin sheath annotation - already reviewed as non-core.
    action: KEEP_AS_NON_CORE
    reason: Same myelin localization as IBA annotation. Related to MBP interaction
      but specialized nervous system function.
    supported_by:
    - reference_id: PMID:19855925
      supporting_text: Structural analysis of the complex between calmodulin and full-length
        myelin basic protein
- term:
    id: GO:0044305
    label: calyx of Held
  evidence_type: IEA
  original_reference_id: GO_REF:0000120
  review:
    summary: Specialized synaptic localization in auditory brainstem.
    action: REMOVE
    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.
    supported_by:
    - reference_id: GO_REF:0000120
      supporting_text: Combined Automated Annotation using Multiple IEA Methods
- term:
    id: GO:0048306
    label: calcium-dependent protein binding
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  review:
    summary: Core molecular function - CALM1 binding to targets is calcium-dependent,
      enabling signal transduction.
    action: ACCEPT
    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.
    supported_by:
    - reference_id: PMID:8631777
      supporting_text: Blocking the Ca2+-induced conformational transitions in calmodulin
        with disulfide bonds
- term:
    id: GO:0050848
    label: regulation of calcium-mediated signaling
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  review:
    summary: Core function as master regulator of calcium signaling pathways.
    action: ACCEPT
    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.
    supported_by:
    - reference_id: PMID:35568036
      supporting_text: A family of conserved bacterial virulence factors dampens interferon
        responses by blocking calcium signaling
- term:
    id: GO:0097225
    label: sperm midpiece
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  review:
    summary: Sperm-specific localization, not core function.
    action: KEEP_AS_NON_CORE
    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.
    supported_by:
    - reference_id: GO_REF:0000107
      supporting_text: Automatic transfer of experimentally verified manual GO annotation
        data to orthologs
- term:
    id: GO:0099523
    label: presynaptic cytosol
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  review:
    summary: Neuronal synaptic localization for neurotransmitter release regulation.
    action: KEEP_AS_NON_CORE
    reason: Valid neuronal localization where CALM1 regulates synaptic vesicle release.
      Based on ortholog evidence. Important for synaptic function but tissue-specific
      rather than core.
    supported_by:
    - reference_id: GO_REF:0000107
      supporting_text: Automatic transfer of experimentally verified manual GO annotation
        data to orthologs
- term:
    id: GO:0140238
    label: presynaptic endocytosis
  evidence_type: IEA
  original_reference_id: GO_REF:0000120
  review:
    summary: Synaptic vesicle recycling function in neurons.
    action: KEEP_AS_NON_CORE
    reason: Valid neuronal function where CALM1 regulates synaptic vesicle endocytosis
      through calcium signaling. Tissue-specific process rather than core ubiquitous
      function.
    supported_by:
    - reference_id: GO_REF:0000120
      supporting_text: Combined Automated Annotation using Multiple IEA Methods
- term:
    id: GO:0141110
    label: transporter inhibitor activity
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  review:
    summary: Too general - specific channel regulation functions are better annotated.
    action: REMOVE
    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.
    supported_by:
    - reference_id: GO_REF:0000107
      supporting_text: Automatic transfer of experimentally verified manual GO annotation
        data to orthologs
- term:
    id: GO:1905913
    label: negative regulation of calcium ion export across plasma membrane
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  review:
    summary: Calcium homeostasis function through pump/exchanger regulation.
    action: KEEP_AS_NON_CORE
    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.
    supported_by:
    - reference_id: GO_REF:0000107
      supporting_text: Automatic transfer of experimentally verified manual GO annotation
        data to orthologs
- term:
    id: GO:0010881
    label: regulation of cardiac muscle contraction by regulation of the release of
      sequestered calcium ion
  evidence_type: IDA
  original_reference_id: PMID:23040497
  review:
    summary: Duplicate IDA annotation - core cardiac function.
    action: ACCEPT
    reason: Same core cardiac function already annotated with IEA. Strong experimental
      evidence from calmodulinopathy study.
    supported_by:
    - reference_id: PMID:23040497
      supporting_text: Mutations in calmodulin cause ventricular tachycardia and sudden
        cardiac death
- term:
    id: GO:1901844
    label: regulation of cell communication by electrical coupling involved in cardiac
      conduction
  evidence_type: IDA
  original_reference_id: PMID:23040497
  review:
    summary: Duplicate IDA annotation - already covered by IEA.
    action: ACCEPT
    reason: Same cardiac conduction function as IEA annotation but with direct experimental
      evidence from human genetics.
    supported_by:
    - reference_id: PMID:23040497
      supporting_text: Catecholaminergic polymorphic ventricular tachycardia (CPVT)
        is a devastating inherited disorder characterized by episodic syncope and/or
        sudden cardiac arrest
- term:
    id: GO:0005246
    label: calcium channel regulator activity
  evidence_type: IDA
  original_reference_id: PMID:20226167
  review:
    summary: Duplicate IDA annotation for calcium channel regulation.
    action: ACCEPT
    reason: Same function as IEA annotation but with direct experimental evidence
      for RyR2 regulation.
    supported_by:
    - reference_id: PMID:20226167
      supporting_text: Defective calmodulin binding to the cardiac ryanodine receptor
        plays a key role in CPVT-associated channel dysfunction
- term:
    id: GO:0010881
    label: regulation of cardiac muscle contraction by regulation of the release of
      sequestered calcium ion
  evidence_type: IDA
  original_reference_id: PMID:20226167
  review:
    summary: Another duplicate - same cardiac function with different IDA evidence.
    action: ACCEPT
    reason: Same core function from different experimental study on CPVT and RyR2
      regulation.
    supported_by:
    - reference_id: PMID:20226167
      supporting_text: 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
- term:
    id: GO:0060291
    label: long-term synaptic potentiation
  evidence_type: TAS
  original_reference_id: PMID:20668654
  review:
    summary: Duplicate annotation with stronger evidence - neuronal function.
    action: KEEP_AS_NON_CORE
    reason: Same LTP function as IEA but with TAS evidence from CaMKII structural
      study. Important for learning/memory but tissue-specific.
    supported_by:
    - reference_id: PMID:20668654
      supporting_text: Structure of the CaMKIIdelta/calmodulin complex reveals the
        molecular mechanism of CaMKII kinase activation
- term:
    id: GO:0097720
    label: calcineurin-mediated signaling
  evidence_type: IDA
  original_reference_id: PMID:8631777
  review:
    summary: Duplicate with direct experimental evidence for calcineurin signaling.
    action: ACCEPT
    reason: Same core function as IBA/IEA annotations but with direct biochemical
      evidence.
    supported_by:
    - reference_id: PMID:8631777
      supporting_text: Blocking the Ca2+-induced conformational transitions in calmodulin
        with disulfide bonds
- term:
    id: GO:0005829
    label: cytosol
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-6786205
  review:
    summary: Cytosolic localization for methylation by KAMKMT.
    action: ACCEPT
    reason: TAS evidence from Reactome for cytosolic localization where CALM1 undergoes
      trimethylation. Core compartment for CALM1 function.
    supported_by:
    - reference_id: Reactome:R-HSA-6786205
      supporting_text: KAMKMT transfers 3xCH3 groups from 3xAdoMet to CALM1
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:11807546
  review:
    summary: Binding to anthrax adenylyl cyclase exotoxin - should be more specific.
    action: MODIFY
    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_replacement_terms:
    - id: GO:0010856
      label: adenylate cyclase activator activity
    supported_by:
    - reference_id: PMID:11807546
      supporting_text: Structural basis for the activation of anthrax adenylyl cyclase
        exotoxin by calmodulin
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:11984006
  review:
    summary: Interaction with Chediak-Higashi protein/LYST - specialized vesicle trafficking
      function.
    action: KEEP_AS_NON_CORE
    reason: IPI evidence (PMID:11984006) shows interaction with CHS protein involved
      in vesicle trafficking. Valid but specialized function, not core to CALM1 primary
      role.
    supported_by:
    - reference_id: PMID:11984006
      supporting_text: The Chediak-Higashi protein interacts with SNARE complex and
        signal transduction proteins
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:19855925
  review:
    summary: Binding to myelin basic protein - relevant for myelin sheath localization.
    action: KEEP_AS_NON_CORE
    reason: IPI evidence (PMID:19855925) demonstrates calmodulin-MBP complex formation.
      Relevant for nervous system function but not core ubiquitous role.
    supported_by:
    - reference_id: PMID:19855925
      supporting_text: Structural analysis of the complex between calmodulin and full-length
        myelin basic protein, an intrinsically disordered molecule
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:27564677
  review:
    summary: Binding to KCNQ/M-channels - more specific annotation available.
    action: REMOVE
    reason: Generic protein binding for KCNQ channel interaction. The voltage-gated
      potassium channel complex annotation (GO:0008076) better captures this specific
      interaction.
    supported_by:
    - reference_id: PMID:27564677
      supporting_text: Structural Insights into the M-Channel Proximal C-Terminus/Calmodulin
        Complex
- term:
    id: GO:0043539
    label: protein serine/threonine kinase activator activity
  evidence_type: IDA
  original_reference_id: PMID:35568036
  review:
    summary: Reactome pathway annotation - see individual pathways for specific functions
    action: ACCEPT
    reason: TAS evidence from curated Reactome pathways. These annotations reflect
      the diverse cellular processes involving CALM1.
    supported_by:
    - reference_id: PMID:35568036
      supporting_text: 2022 May 13. A family of conserved bacterial virulence factors
        dampens interferon responses by blocking calcium signaling.
- term:
    id: GO:0005509
    label: calcium ion binding
  evidence_type: IDA
  original_reference_id: PMID:35568036
  review:
    summary: Reactome pathway annotation - see individual pathways for specific functions
    action: ACCEPT
    reason: TAS evidence from curated Reactome pathways. These annotations reflect
      the diverse cellular processes involving CALM1.
    supported_by:
    - reference_id: PMID:35568036
      supporting_text: 2022 May 13. A family of conserved bacterial virulence factors
        dampens interferon responses by blocking calcium signaling.
- term:
    id: GO:0035458
    label: cellular response to interferon-beta
  evidence_type: IDA
  original_reference_id: PMID:35568036
  review:
    summary: CALM1 mediates interferon signaling through CaMKII and JAK/STAT pathway
      activation.
    action: ACCEPT
    reason: IDA evidence (PMID:35568036) demonstrates CALM1 role in IFN-β response
      through calcium signaling to CaMKII and JAK/STAT. Bacterial pathogens target
      this pathway by sequestering calmodulin.
    supported_by:
    - reference_id: PMID:35568036
      supporting_text: 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
- term:
    id: GO:0043539
    label: protein serine/threonine kinase activator activity
  evidence_type: IDA
  original_reference_id: PMID:14722083
  review:
    summary: Reactome pathway annotation - see individual pathways for specific functions
    action: ACCEPT
    reason: TAS evidence from curated Reactome pathways. These annotations reflect
      the diverse cellular processes involving CALM1.
    supported_by:
    - reference_id: PMID:14722083
      supporting_text: 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.
- term:
    id: GO:0046427
    label: positive regulation of receptor signaling pathway via JAK-STAT
  evidence_type: IDA
  original_reference_id: PMID:11972023
  review:
    summary: CALM1/CaMKII required for STAT1 phosphorylation in interferon response.
    action: ACCEPT
    reason: IDA evidence shows calcium/calmodulin and CaMKII are required for IFN-γ-induced
      STAT1 Ser-727 phosphorylation. Important for immune signaling.
    supported_by:
    - reference_id: PMID:11972023
      supporting_text: Requirement of Ca2+ and CaMKII for Stat1 Ser-727 phosphorylation
        in response to IFN-gamma
- term:
    id: GO:0046427
    label: positive regulation of receptor signaling pathway via JAK-STAT
  evidence_type: IDA
  original_reference_id: PMID:35568036
  review:
    summary: Reactome pathway annotation - see individual pathways for specific functions
    action: ACCEPT
    reason: TAS evidence from curated Reactome pathways. These annotations reflect
      the diverse cellular processes involving CALM1.
    supported_by:
    - reference_id: PMID:35568036
      supporting_text: 2022 May 13. A family of conserved bacterial virulence factors
        dampens interferon responses by blocking calcium signaling.
- term:
    id: GO:0071346
    label: cellular response to type II interferon
  evidence_type: IDA
  original_reference_id: PMID:11972023
  review:
    summary: Reactome pathway annotation - see individual pathways for specific functions
    action: ACCEPT
    reason: TAS evidence from curated Reactome pathways. These annotations reflect
      the diverse cellular processes involving CALM1.
    supported_by:
    - reference_id: PMID:11972023
      supporting_text: Requirement of Ca2+ and CaMKII for Stat1 Ser-727 phosphorylation
        in response to IFN-gamma.
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:28890335
  review:
    summary: EPG-3/VMP1 interaction for autophagy - more specific annotations present.
    action: REMOVE
    reason: Generic protein binding redundant with more specific autophagosome and
      organelle tethering annotations from same paper that better describe the functional
      interaction.
    supported_by:
    - reference_id: PMID:28890335
      supporting_text: The ER-Localized Transmembrane Protein EPG-3/VMP1 Regulates
        SERCA Activity
- term:
    id: GO:0016240
    label: autophagosome membrane docking
  evidence_type: IDA
  original_reference_id: PMID:28890335
  review:
    summary: CALM1 involved in ER-autophagosome contacts through EPG-3/VMP1 regulation.
    action: KEEP_AS_NON_CORE
    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.
    supported_by:
    - reference_id: PMID:28890335
      supporting_text: The ER-Localized Transmembrane Protein EPG-3/VMP1 Regulates
        SERCA Activity to Control ER-Isolation Membrane Contacts for Autophagosome
        Formation
- term:
    id: GO:0140056
    label: organelle localization by membrane tethering
  evidence_type: IDA
  original_reference_id: PMID:28890335
  review:
    summary: Reactome pathway annotation - see individual pathways for specific functions
    action: ACCEPT
    reason: TAS evidence from curated Reactome pathways. These annotations reflect
      the diverse cellular processes involving CALM1.
    supported_by:
    - reference_id: PMID:28890335
      supporting_text: Epub 2017 Sep 7. The ER-Localized Transmembrane Protein EPG-3/VMP1
        Regulates SERCA Activity to Control ER-Isolation Membrane Contacts for Autophagosome
        Formation.
- term:
    id: GO:1990456
    label: mitochondrion-endoplasmic reticulum membrane tethering
  evidence_type: IDA
  original_reference_id: PMID:28890335
  review:
    summary: Reactome pathway annotation - see individual pathways for specific functions
    action: ACCEPT
    reason: TAS evidence from curated Reactome pathways. These annotations reflect
      the diverse cellular processes involving CALM1.
    supported_by:
    - reference_id: PMID:28890335
      supporting_text: Epub 2017 Sep 7. The ER-Localized Transmembrane Protein EPG-3/VMP1
        Regulates SERCA Activity to Control ER-Isolation Membrane Contacts for Autophagosome
        Formation.
- term:
    id: GO:0005509
    label: calcium ion binding
  evidence_type: IDA
  original_reference_id: PMID:31454269
  review:
    summary: Reactome pathway annotation - see individual pathways for specific functions
    action: ACCEPT
    reason: TAS evidence from curated Reactome pathways. These annotations reflect
      the diverse cellular processes involving CALM1.
    supported_by:
    - reference_id: PMID:31454269
      supporting_text: Genetic Mosaicism in Calmodulinopathy.
- term:
    id: GO:0098901
    label: regulation of cardiac muscle cell action potential
  evidence_type: IMP
  original_reference_id: PMID:31454269
  review:
    summary: Core cardiac function - CALM1 mutations disrupt action potential regulation
      causing arrhythmias.
    action: ACCEPT
    reason: IMP evidence (PMID:31454269) from genetic mosaicism study shows CALM1
      mutations directly affect cardiac action potentials. Essential for normal cardiac
      electrophysiology.
    supported_by:
    - reference_id: PMID:31454269
      supporting_text: Genetic Mosaicism in Calmodulinopathy
- term:
    id: GO:1901842
    label: negative regulation of high voltage-gated calcium channel activity
  evidence_type: IMP
  original_reference_id: PMID:31454269
  review:
    summary: Important calcium channel regulation - CALM1 negatively regulates L-type
      calcium channels.
    action: ACCEPT
    reason: IMP evidence (PMID:31454269) demonstrates CALM1 regulation of high voltage-gated
      calcium channels. Mutations disrupt this regulation contributing to calmodulinopathies.
    supported_by:
    - reference_id: PMID:31454269
      supporting_text: Genetic Mosaicism in Calmodulinopathy
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:30021165
  review:
    summary: KIF1A motor protein interaction for vesicle transport.
    action: KEEP_AS_NON_CORE
    reason: IPI evidence (PMID:30021165) shows CALM1 regulates KIF1A-driven dense
      core vesicle transport. Specialized neuronal function for neurosecretion.
    supported_by:
    - reference_id: PMID:30021165
      supporting_text: 'Regulation of KIF1A-Driven Dense Core Vesicle Transport: Ca(2+)/CaM
        Controls DCV Binding and Liprin-α/TANC2 Recruits DCVs to Postsynaptic Sites'
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:30287853
  review:
    summary: Reactome pathway annotation - see individual pathways for specific functions
    action: ACCEPT
    reason: TAS evidence from curated Reactome pathways. These annotations reflect
      the diverse cellular processes involving CALM1.
    supported_by:
    - reference_id: PMID:30287853
      supporting_text: Calcineurin B homologous protein 3 binds with high affinity
        to the CHP binding domain of the human sodium/proton exchanger NHE1.
- term:
    id: GO:0010856
    label: adenylate cyclase activator activity
  evidence_type: IDA
  original_reference_id: PMID:11807546
  review:
    summary: Reactome pathway annotation - see individual pathways for specific functions
    action: ACCEPT
    reason: TAS evidence from curated Reactome pathways. These annotations reflect
      the diverse cellular processes involving CALM1.
    supported_by:
    - reference_id: PMID:11807546
      supporting_text: Structural basis for the activation of anthrax adenylyl cyclase
        exotoxin by calmodulin.
- term:
    id: GO:0034704
    label: calcium channel complex
  evidence_type: IDA
  original_reference_id: PMID:23040497
  review:
    summary: Reactome pathway annotation - see individual pathways for specific functions
    action: ACCEPT
    reason: TAS evidence from curated Reactome pathways. These annotations reflect
      the diverse cellular processes involving CALM1.
    supported_by:
    - reference_id: PMID:23040497
      supporting_text: Mutations in calmodulin cause ventricular tachycardia and sudden
        cardiac death.
- term:
    id: GO:0000922
    label: spindle pole
  evidence_type: IDA
  original_reference_id: PMID:16760425
  review:
    summary: Reactome pathway annotation - see individual pathways for specific functions
    action: ACCEPT
    reason: TAS evidence from curated Reactome pathways. These annotations reflect
      the diverse cellular processes involving CALM1.
    supported_by:
    - reference_id: PMID:16760425
      supporting_text: Jun 7. CP110 cooperates with two calcium-binding proteins to
        regulate cytokinesis and genome stability.
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:10692436
  review:
    summary: Binding to erythrocyte protein 4.1 for membrane-cytoskeleton linkage.
    action: KEEP_AS_NON_CORE
    reason: IPI evidence (PMID:10692436) shows calcium-dependent and independent binding
      to protein 4.1. Specialized erythrocyte function for membrane-cytoskeleton regulation.
    supported_by:
    - reference_id: PMID:10692436
      supporting_text: Ca(2+)-dependent and Ca(2+)-independent calmodulin binding
        sites in erythrocyte protein 4.1
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:15140941
  review:
    summary: Binding to Ca2+-binding protein-1/CaBP1 and Cav1.2 channels.
    action: MODIFY
    reason: While interaction is valid, this relates to calcium channel regulation
      already covered by GO:0005246 and GO:0034704. Generic protein binding uninformative.
    proposed_replacement_terms:
    - id: GO:0005246
      label: calcium channel regulator activity
    supported_by:
    - reference_id: PMID:15140941
      supporting_text: Ca2+-binding protein-1 facilitates and forms a postsynaptic
        complex with Cav1.2 (L-type) Ca2+ channels
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:15632291
  review:
    summary: Binding to HIV Nef protein - pathogen interaction.
    action: KEEP_AS_NON_CORE
    reason: IPI evidence (PMID:15632291) shows interaction with HIV Nef myristoyl
      moiety. Example of pathogen hijacking CALM1 but not core function.
    supported_by:
    - reference_id: PMID:15632291
      supporting_text: Myristoyl moiety of HIV Nef is involved in regulation of the
        interaction with calmodulin in vivo
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:16760425
  review:
    summary: CP110 binding for cytokinesis - better captured by specific annotations.
    action: REMOVE
    reason: CP110 interaction already well-covered by centrosome localization and
      cytokinesis regulation annotations. Generic protein binding redundant.
    supported_by:
    - reference_id: PMID:16760425
      supporting_text: CP110 cooperates with two calcium-binding proteins to regulate
        cytokinesis and genome stability
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:21299499
  review:
    summary: IQGAP binding for cytoskeletal regulation.
    action: KEEP_AS_NON_CORE
    reason: IPI evidence (PMID:21299499) shows IQ-motif binding to IQGAP2/3. Important
      for cytoskeletal regulation but not core universal function.
    supported_by:
    - reference_id: PMID:21299499
      supporting_text: 'IQ-motif selectivity in human IQGAP2 and IQGAP3: binding of
        calmodulin and myosin essential light chain'
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:3111527
  review:
    summary: Interaction with tau proteins and melittin.
    action: KEEP_AS_NON_CORE
    reason: IPI evidence (PMID:3111527) shows interaction with tau proteins. Relevant
      for neurodegeneration but not core function.
    supported_by:
    - reference_id: PMID:3111527
      supporting_text: 'Comparison of S100b protein with calmodulin: interactions
        with melittin and microtubule-associated tau proteins'
- term:
    id: GO:0005634
    label: nucleus
  evidence_type: HDA
  original_reference_id: PMID:21630459
  review:
    summary: Sperm nuclear localization from proteomics.
    action: KEEP_AS_NON_CORE
    reason: HDA evidence from sperm nucleus proteomics. Specialized reproductive cell
      localization, not core.
    supported_by:
    - reference_id: PMID:21630459
      supporting_text: Proteomic characterization of the human sperm nucleus
- term:
    id: GO:0005737
    label: cytoplasm
  evidence_type: TAS
  original_reference_id: PMID:10899953
  review:
    summary: Core cytoplasmic localization with TAS evidence.
    action: ACCEPT
    reason: TAS evidence confirms primary cytoplasmic localization where CALM1 performs
      most functions.
    supported_by:
    - reference_id: PMID:10899953
      supporting_text: Calmodulin regulation of basal and agonist-stimulated G protein
        coupling by the mu-opioid receptor
- term:
    id: GO:0005813
    label: centrosome
  evidence_type: IDA
  original_reference_id: PMID:16760425
  review:
    summary: Direct experimental evidence for centrosomal localization.
    action: ACCEPT
    reason: IDA evidence directly demonstrates centrosomal localization and functional
      importance for cytokinesis.
    supported_by:
    - reference_id: PMID:16760425
      supporting_text: CP110 cooperates with two calcium-binding proteins to regulate
        cytokinesis and genome stability
- term:
    id: GO:0005876
    label: spindle microtubule
  evidence_type: IDA
  original_reference_id: PMID:16760425
  review:
    summary: Direct evidence for spindle microtubule localization.
    action: ACCEPT
    reason: IDA evidence confirms spindle microtubule localization essential for mitosis
      and cytokinesis.
    supported_by:
    - reference_id: PMID:16760425
      supporting_text: depletion leads to a failure at a late stage of cytokinesis
        and the formation of binucleate cells
- term:
    id: GO:0005886
    label: plasma membrane
  evidence_type: TAS
  original_reference_id: PMID:10899953
  review:
    summary: Plasma membrane localization for GPCR regulation.
    action: ACCEPT
    reason: TAS evidence shows plasma membrane localization for G protein-coupled
      receptor regulation. Important for membrane-associated signaling.
    supported_by:
    - reference_id: PMID:10899953
      supporting_text: Calmodulin regulation of basal and agonist-stimulated G protein
        coupling by the mu-opioid receptor
- term:
    id: GO:0007186
    label: G protein-coupled receptor signaling pathway
  evidence_type: TAS
  original_reference_id: PMID:10899953
  review:
    summary: CALM1 regulates GPCR signaling, particularly opioid receptors.
    action: ACCEPT
    reason: TAS evidence shows CALM1 regulation of mu-opioid receptor and GPCR signaling.
      Important signaling pathway regulation.
    supported_by:
    - reference_id: PMID:10899953
      supporting_text: Calmodulin regulation of basal and agonist-stimulated G protein
        coupling by the mu-opioid receptor
- term:
    id: GO:0021762
    label: substantia nigra development
  evidence_type: HEP
  original_reference_id: PMID:22926577
  review:
    summary: Expression in substantia nigra but not functionally validated for development.
    action: REMOVE
    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.
    supported_by:
    - reference_id: PMID:22926577
      supporting_text: Quantitative proteomic analysis of human substantia nigra in
        Alzheimer's disease, Huntington's disease and Multiple sclerosis
- term:
    id: GO:0031982
    label: vesicle
  evidence_type: HDA
  original_reference_id: PMID:19190083
  review:
    summary: Presence in exosome-like vesicles from epithelium.
    action: KEEP_AS_NON_CORE
    reason: HDA evidence from exosome proteomics. Reflects vesicular trafficking role
      but not core function.
    supported_by:
    - reference_id: PMID:19190083
      supporting_text: 'Characterization of exosome-like vesicles released from human
        tracheobronchial ciliated epithelium: a possible role in innate defense'
- term:
    id: GO:0032465
    label: regulation of cytokinesis
  evidence_type: IMP
  original_reference_id: PMID:16760425
  review:
    summary: Direct functional evidence for cytokinesis regulation.
    action: ACCEPT
    reason: IMP evidence shows CALM1 depletion causes cytokinesis failure. Essential
      for proper cell division completion.
    supported_by:
    - reference_id: PMID:16760425
      supporting_text: 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
- term:
    id: GO:0005509
    label: calcium ion binding
  evidence_type: IDA
  original_reference_id: PMID:11807546
  review:
    summary: Duplicate calcium binding with anthrax toxin study evidence.
    action: ACCEPT
    reason: Core function with IDA evidence from structural study with anthrax adenylyl
      cyclase.
    supported_by:
    - reference_id: PMID:11807546
      supporting_text: Structural basis for the activation of anthrax adenylyl cyclase
        exotoxin by calmodulin
- term:
    id: GO:0032991
    label: protein-containing complex
  evidence_type: IDA
  original_reference_id: PMID:19855925
  review:
    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.
    action: ACCEPT
    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.
    supported_by:
    - reference_id: PMID:19855925
      supporting_text: Structural analysis of the complex between calmodulin and full-length
        myelin basic protein
- term:
    id: GO:1902494
    label: catalytic complex
  evidence_type: IDA
  original_reference_id: PMID:11807546
  review:
    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.
    action: ACCEPT
    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.
    supported_by:
    - reference_id: PMID:11807546
      supporting_text: Structural basis for the activation of anthrax adenylyl cyclase
        exotoxin by calmodulin
- term:
    id: GO:0005576
    label: extracellular region
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-482772
  review:
    summary: Extracellular release from platelets.
    action: KEEP_AS_NON_CORE
    reason: TAS from Reactome showing platelet release of cytosolic components. Specialized
      platelet function, not core.
    supported_by:
    - reference_id: Reactome:R-HSA-482772
      supporting_text: Release of platelet cytosolic components
- term:
    id: GO:0005654
    label: nucleoplasm
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-111915
  review:
    summary: Nuclear localization for CAMK4 regulation.
    action: ACCEPT
    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.
    supported_by:
    - reference_id: Reactome:R-HSA-111915
      supporting_text: CAMK4 autophosphorylates
- term:
    id: GO:0005654
    label: nucleoplasm
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-2730867
  review:
    summary: Reactome pathway annotation - see individual pathways for specific functions
    action: ACCEPT
    reason: TAS evidence from curated Reactome pathways. These annotations reflect
      the diverse cellular processes involving CALM1.
- term:
    id: GO:0005654
    label: nucleoplasm
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-442749
  review:
    summary: Reactome pathway annotation - see individual pathways for specific functions
    action: ACCEPT
    reason: TAS evidence from curated Reactome pathways. These annotations reflect
      the diverse cellular processes involving CALM1.
- term:
    id: GO:0005654
    label: nucleoplasm
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-4551465
  review:
    summary: Reactome pathway annotation - see individual pathways for specific functions
    action: ACCEPT
    reason: TAS evidence from curated Reactome pathways. These annotations reflect
      the diverse cellular processes involving CALM1.
- term:
    id: GO:0005654
    label: nucleoplasm
  evidence_type: TAS
  original_reference_id: Reactome:R-NUL-9618916
  review:
    summary: Reactome pathway annotation - see individual pathways for specific functions
    action: ACCEPT
    reason: TAS evidence from curated Reactome pathways. These annotations reflect
      the diverse cellular processes involving CALM1.
- term:
    id: GO:0005654
    label: nucleoplasm
  evidence_type: TAS
  original_reference_id: Reactome:R-NUL-9619177
  review:
    summary: Reactome pathway annotation - see individual pathways for specific functions
    action: ACCEPT
    reason: TAS evidence from curated Reactome pathways. These annotations reflect
      the diverse cellular processes involving CALM1.
- term:
    id: GO:0005886
    label: plasma membrane
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-202110
  review:
    summary: Reactome pathway annotation - see individual pathways for specific functions
    action: ACCEPT
    reason: TAS evidence from curated Reactome pathways. These annotations reflect
      the diverse cellular processes involving CALM1.
- term:
    id: GO:0005886
    label: plasma membrane
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-202111
  review:
    summary: Reactome pathway annotation - see individual pathways for specific functions
    action: ACCEPT
    reason: TAS evidence from curated Reactome pathways. These annotations reflect
      the diverse cellular processes involving CALM1.
- term:
    id: GO:0005886
    label: plasma membrane
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-202129
  review:
    summary: Reactome pathway annotation - see individual pathways for specific functions
    action: ACCEPT
    reason: TAS evidence from curated Reactome pathways. These annotations reflect
      the diverse cellular processes involving CALM1.
- term:
    id: GO:0005886
    label: plasma membrane
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-202137
  review:
    summary: Reactome pathway annotation - see individual pathways for specific functions
    action: ACCEPT
    reason: TAS evidence from curated Reactome pathways. These annotations reflect
      the diverse cellular processes involving CALM1.
- term:
    id: GO:0005886
    label: plasma membrane
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-202144
  review:
    summary: Reactome pathway annotation - see individual pathways for specific functions
    action: ACCEPT
    reason: TAS evidence from curated Reactome pathways. These annotations reflect
      the diverse cellular processes involving CALM1.
- term:
    id: GO:0005886
    label: plasma membrane
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-5626549
  review:
    summary: Reactome pathway annotation for CALM1 in plasma membrane.
    action: ACCEPT
    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.
    supported_by:
    - reference_id: Reactome:R-HSA-2730867
      supporting_text: Translocation of CaN:CaM:NFAT to nucleus
- term:
    id: GO:0005829
    label: cytosol
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-111966
  review:
    summary: Reactome pathway annotation - see individual pathways for specific functions
    action: ACCEPT
    reason: TAS evidence from curated Reactome pathways. These annotations reflect
      the diverse cellular processes involving CALM1.
- term:
    id: GO:0005829
    label: cytosol
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-1497784
  review:
    summary: Reactome pathway annotation - see individual pathways for specific functions
    action: ACCEPT
    reason: TAS evidence from curated Reactome pathways. These annotations reflect
      the diverse cellular processes involving CALM1.
- term:
    id: GO:0005829
    label: cytosol
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-1497796
  review:
    summary: Reactome pathway annotation - see individual pathways for specific functions
    action: ACCEPT
    reason: TAS evidence from curated Reactome pathways. These annotations reflect
      the diverse cellular processes involving CALM1.
- term:
    id: GO:0005829
    label: cytosol
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-1497810
  review:
    summary: Reactome pathway annotation - see individual pathways for specific functions
    action: ACCEPT
    reason: TAS evidence from curated Reactome pathways. These annotations reflect
      the diverse cellular processes involving CALM1.
- term:
    id: GO:0005829
    label: cytosol
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-1855153
  review:
    summary: Reactome pathway annotation - see individual pathways for specific functions
    action: ACCEPT
    reason: TAS evidence from curated Reactome pathways. These annotations reflect
      the diverse cellular processes involving CALM1.
- term:
    id: GO:0005829
    label: cytosol
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-202110
  review:
    summary: Reactome pathway annotation - see individual pathways for specific functions
    action: ACCEPT
    reason: TAS evidence from curated Reactome pathways. These annotations reflect
      the diverse cellular processes involving CALM1.
- term:
    id: GO:0005829
    label: cytosol
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-202111
  review:
    summary: Reactome pathway annotation - see individual pathways for specific functions
    action: ACCEPT
    reason: TAS evidence from curated Reactome pathways. These annotations reflect
      the diverse cellular processes involving CALM1.
- term:
    id: GO:0005829
    label: cytosol
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-202127
  review:
    summary: Reactome pathway annotation - see individual pathways for specific functions
    action: ACCEPT
    reason: TAS evidence from curated Reactome pathways. These annotations reflect
      the diverse cellular processes involving CALM1.
- term:
    id: GO:0005829
    label: cytosol
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-202129
  review:
    summary: Reactome pathway annotation - see individual pathways for specific functions
    action: ACCEPT
    reason: TAS evidence from curated Reactome pathways. These annotations reflect
      the diverse cellular processes involving CALM1.
- term:
    id: GO:0005829
    label: cytosol
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-2025890
  review:
    summary: Reactome pathway annotation - see individual pathways for specific functions
    action: ACCEPT
    reason: TAS evidence from curated Reactome pathways. These annotations reflect
      the diverse cellular processes involving CALM1.
- term:
    id: GO:0005829
    label: cytosol
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-2730849
  review:
    summary: Reactome pathway annotation - see individual pathways for specific functions
    action: ACCEPT
    reason: TAS evidence from curated Reactome pathways. These annotations reflect
      the diverse cellular processes involving CALM1.
- term:
    id: GO:0005829
    label: cytosol
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-2730867
  review:
    summary: Reactome pathway annotation - see individual pathways for specific functions
    action: ACCEPT
    reason: TAS evidence from curated Reactome pathways. These annotations reflect
      the diverse cellular processes involving CALM1.
- term:
    id: GO:0005829
    label: cytosol
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-2730872
  review:
    summary: Reactome pathway annotation - see individual pathways for specific functions
    action: ACCEPT
    reason: TAS evidence from curated Reactome pathways. These annotations reflect
      the diverse cellular processes involving CALM1.
- term:
    id: GO:0005829
    label: cytosol
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-3229181
  review:
    summary: Reactome pathway annotation - see individual pathways for specific functions
    action: ACCEPT
    reason: TAS evidence from curated Reactome pathways. These annotations reflect
      the diverse cellular processes involving CALM1.
- term:
    id: GO:0005829
    label: cytosol
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-4332358
  review:
    summary: Reactome pathway annotation - see individual pathways for specific functions
    action: ACCEPT
    reason: TAS evidence from curated Reactome pathways. These annotations reflect
      the diverse cellular processes involving CALM1.
- term:
    id: GO:0005829
    label: cytosol
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-4332359
  review:
    summary: Reactome pathway annotation - see individual pathways for specific functions
    action: ACCEPT
    reason: TAS evidence from curated Reactome pathways. These annotations reflect
      the diverse cellular processes involving CALM1.
- term:
    id: GO:0005829
    label: cytosol
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-4332363
  review:
    summary: Reactome pathway annotation - see individual pathways for specific functions
    action: ACCEPT
    reason: TAS evidence from curated Reactome pathways. These annotations reflect
      the diverse cellular processes involving CALM1.
- term:
    id: GO:0005829
    label: cytosol
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-445797
  review:
    summary: Reactome pathway annotation - see individual pathways for specific functions
    action: ACCEPT
    reason: TAS evidence from curated Reactome pathways. These annotations reflect
      the diverse cellular processes involving CALM1.
- term:
    id: GO:0005829
    label: cytosol
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-445813
  review:
    summary: Reactome pathway annotation - see individual pathways for specific functions
    action: ACCEPT
    reason: TAS evidence from curated Reactome pathways. These annotations reflect
      the diverse cellular processes involving CALM1.
- term:
    id: GO:0005829
    label: cytosol
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-451283
  review:
    summary: Reactome pathway annotation - see individual pathways for specific functions
    action: ACCEPT
    reason: TAS evidence from curated Reactome pathways. These annotations reflect
      the diverse cellular processes involving CALM1.
- term:
    id: GO:0005829
    label: cytosol
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-451311
  review:
    summary: Reactome pathway annotation - see individual pathways for specific functions
    action: ACCEPT
    reason: TAS evidence from curated Reactome pathways. These annotations reflect
      the diverse cellular processes involving CALM1.
- term:
    id: GO:0005829
    label: cytosol
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-4551451
  review:
    summary: Reactome pathway annotation - see individual pathways for specific functions
    action: ACCEPT
    reason: TAS evidence from curated Reactome pathways. These annotations reflect
      the diverse cellular processes involving CALM1.
- term:
    id: GO:0005829
    label: cytosol
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-4551465
  review:
    summary: Reactome pathway annotation - see individual pathways for specific functions
    action: ACCEPT
    reason: TAS evidence from curated Reactome pathways. These annotations reflect
      the diverse cellular processes involving CALM1.
- term:
    id: GO:0005829
    label: cytosol
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-482772
  review:
    summary: Reactome pathway annotation - see individual pathways for specific functions
    action: ACCEPT
    reason: TAS evidence from curated Reactome pathways. These annotations reflect
      the diverse cellular processes involving CALM1.
- term:
    id: GO:0005829
    label: cytosol
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-5672965
  review:
    summary: Reactome pathway annotation - see individual pathways for specific functions
    action: ACCEPT
    reason: TAS evidence from curated Reactome pathways. These annotations reflect
      the diverse cellular processes involving CALM1.
- term:
    id: GO:0005829
    label: cytosol
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-71541
  review:
    summary: Reactome pathway annotation - see individual pathways for specific functions
    action: ACCEPT
    reason: TAS evidence from curated Reactome pathways. These annotations reflect
      the diverse cellular processes involving CALM1.
- term:
    id: GO:0005829
    label: cytosol
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-71588
  review:
    summary: Reactome pathway annotation - see individual pathways for specific functions
    action: ACCEPT
    reason: TAS evidence from curated Reactome pathways. These annotations reflect
      the diverse cellular processes involving CALM1.
- term:
    id: GO:0005829
    label: cytosol
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-9618785
  review:
    summary: Reactome pathway annotation - see individual pathways for specific functions
    action: ACCEPT
    reason: TAS evidence from curated Reactome pathways. These annotations reflect
      the diverse cellular processes involving CALM1.
- term:
    id: GO:0005829
    label: cytosol
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-9619355
  review:
    summary: Reactome pathway annotation - see individual pathways for specific functions
    action: ACCEPT
    reason: TAS evidence from curated Reactome pathways. These annotations reflect
      the diverse cellular processes involving CALM1.
- term:
    id: GO:0005829
    label: cytosol
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-9619376
  review:
    summary: Reactome pathway annotation - see individual pathways for specific functions
    action: ACCEPT
    reason: TAS evidence from curated Reactome pathways. These annotations reflect
      the diverse cellular processes involving CALM1.
- term:
    id: GO:0005829
    label: cytosol
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-9653585
  review:
    summary: Reactome pathway annotation - see individual pathways for specific functions
    action: ACCEPT
    reason: TAS evidence from curated Reactome pathways. These annotations reflect
      the diverse cellular processes involving CALM1.
- term:
    id: GO:0005829
    label: cytosol
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-9654521
  review:
    summary: Reactome pathway annotation - see individual pathways for specific functions
    action: ACCEPT
    reason: TAS evidence from curated Reactome pathways. These annotations reflect
      the diverse cellular processes involving CALM1.
- term:
    id: GO:0005829
    label: cytosol
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-9654523
  review:
    summary: Reactome pathway annotation - see individual pathways for specific functions
    action: ACCEPT
    reason: TAS evidence from curated Reactome pathways. These annotations reflect
      the diverse cellular processes involving CALM1.
- term:
    id: GO:0005829
    label: cytosol
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-9654525
  review:
    summary: Reactome pathway annotation - see individual pathways for specific functions
    action: ACCEPT
    reason: TAS evidence from curated Reactome pathways. These annotations reflect
      the diverse cellular processes involving CALM1.
- term:
    id: GO:0005829
    label: cytosol
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-9654533
  review:
    summary: Reactome pathway annotation - see individual pathways for specific functions
    action: ACCEPT
    reason: TAS evidence from curated Reactome pathways. These annotations reflect
      the diverse cellular processes involving CALM1.
- term:
    id: GO:0005829
    label: cytosol
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-9865670
  review:
    summary: Reactome pathway annotation - see individual pathways for specific functions
    action: ACCEPT
    reason: TAS evidence from curated Reactome pathways. These annotations reflect
      the diverse cellular processes involving CALM1.
- term:
    id: GO:0005829
    label: cytosol
  evidence_type: TAS
  original_reference_id: Reactome:R-NUL-9617449
  review:
    summary: Reactome pathway annotation - see individual pathways for specific functions
    action: ACCEPT
    reason: TAS evidence from curated Reactome pathways. These annotations reflect
      the diverse cellular processes involving CALM1.
- term:
    id: GO:0005829
    label: cytosol
  evidence_type: TAS
  original_reference_id: Reactome:R-NUL-9619243
  review:
    summary: Reactome pathway annotation - see individual pathways for specific functions
    action: ACCEPT
    reason: TAS evidence from curated Reactome pathways. These annotations reflect
      the diverse cellular processes involving CALM1.
- term:
    id: GO:0005829
    label: cytosol
  evidence_type: TAS
  original_reference_id: Reactome:R-NUL-9619396
  review:
    summary: Reactome pathway annotation - see individual pathways for specific functions
    action: ACCEPT
    reason: TAS evidence from curated Reactome pathways. These annotations reflect
      the diverse cellular processes involving CALM1.
- term:
    id: GO:0005829
    label: cytosol
  evidence_type: TAS
  original_reference_id: Reactome:R-NUL-9619413
  review:
    summary: Reactome pathway annotation - see individual pathways for specific functions
    action: ACCEPT
    reason: TAS evidence from curated Reactome pathways. These annotations reflect
      the diverse cellular processes involving CALM1.
- term:
    id: GO:0002027
    label: regulation of heart rate
  evidence_type: IMP
  original_reference_id: PMID:23040497
  review:
    summary: Duplicate with IMP evidence for core cardiac function.
    action: ACCEPT
    reason: IMP evidence from calmodulinopathy study directly demonstrates role in
      heart rate regulation. CALM1 mutations cause arrhythmias.
    supported_by:
    - reference_id: PMID:23040497
      supporting_text: Mutations in calmodulin cause ventricular tachycardia and sudden
        cardiac death
- term:
    id: GO:0005509
    label: calcium ion binding
  evidence_type: IDA
  original_reference_id: PMID:23040497
  review:
    summary: Another duplicate with IDA evidence from calmodulinopathy study.
    action: ACCEPT
    reason: Core function with direct experimental evidence from disease mutation
      study.
    supported_by:
    - reference_id: PMID:23040497
      supporting_text: Both CALM1 substitutions demonstrated compromised calcium binding
- term:
    id: GO:0005509
    label: calcium ion binding
  evidence_type: IDA
  original_reference_id: PMID:7607248
  review:
    summary: Duplicate with IDA evidence from titin kinase study.
    action: ACCEPT
    reason: Core function demonstrated in cardiac titin kinase binding study.
    supported_by:
    - reference_id: PMID:7607248
      supporting_text: A calmodulin-binding sequence in the C-terminus of human cardiac
        titin kinase
- term:
    id: GO:0005509
    label: calcium ion binding
  evidence_type: IDA
  original_reference_id: PMID:8631777
  review:
    summary: Duplicate with IDA evidence from calmodulin conformational study.
    action: ACCEPT
    reason: Core function with biochemical evidence on calcium-induced conformational
      changes.
    supported_by:
    - reference_id: PMID:8631777
      supporting_text: Blocking the Ca2+-induced conformational transitions in calmodulin
        with disulfide bonds
- term:
    id: GO:0005513
    label: detection of calcium ion
  evidence_type: IMP
  original_reference_id: PMID:23040497
  review:
    summary: Core calcium sensing with IMP evidence from disease study.
    action: ACCEPT
    reason: Functional evidence shows CALM1 mutations impair calcium sensing causing
      cardiac disease.
    supported_by:
    - reference_id: PMID:23040497
      supporting_text: 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
- term:
    id: GO:0010880
    label: regulation of release of sequestered calcium ion into cytosol by sarcoplasmic
      reticulum
  evidence_type: IDA
  original_reference_id: PMID:20226167
  review:
    summary: Reactome pathway annotation - see individual pathways for specific functions
    action: ACCEPT
    reason: TAS evidence from curated Reactome pathways. These annotations reflect
      the diverse cellular processes involving CALM1.
    supported_by:
    - reference_id: PMID:20226167
      supporting_text: Defective calmodulin binding to the cardiac ryanodine receptor
        plays a key role in CPVT-associated channel dysfunction.
- term:
    id: GO:0019901
    label: protein kinase binding
  evidence_type: IPI
  original_reference_id: PMID:20668654
  review:
    summary: Reactome pathway annotation - see individual pathways for specific functions
    action: ACCEPT
    reason: TAS evidence from curated Reactome pathways. These annotations reflect
      the diverse cellular processes involving CALM1.
    supported_by:
    - reference_id: PMID:20668654
      supporting_text: Structure of the CaMKIIdelta/calmodulin complex reveals the
        molecular mechanism of CaMKII kinase activation.
- term:
    id: GO:0030017
    label: sarcomere
  evidence_type: IDA
  original_reference_id: PMID:20226167
  review:
    summary: Reactome pathway annotation - see individual pathways for specific functions
    action: ACCEPT
    reason: TAS evidence from curated Reactome pathways. These annotations reflect
      the diverse cellular processes involving CALM1.
    supported_by:
    - reference_id: PMID:20226167
      supporting_text: Defective calmodulin binding to the cardiac ryanodine receptor
        plays a key role in CPVT-associated channel dysfunction.
- term:
    id: GO:0031432
    label: titin binding
  evidence_type: IPI
  original_reference_id: PMID:7607248
  review:
    summary: Reactome pathway annotation - see individual pathways for specific functions
    action: ACCEPT
    reason: TAS evidence from curated Reactome pathways. These annotations reflect
      the diverse cellular processes involving CALM1.
    supported_by:
    - reference_id: PMID:7607248
      supporting_text: A calmodulin-binding sequence in the C-terminus of human cardiac
        titin kinase.
- term:
    id: GO:0043539
    label: protein serine/threonine kinase activator activity
  evidence_type: TAS
  original_reference_id: PMID:20668654
  review:
    summary: Reactome pathway annotation - see individual pathways for specific functions
    action: ACCEPT
    reason: TAS evidence from curated Reactome pathways. These annotations reflect
      the diverse cellular processes involving CALM1.
    supported_by:
    - reference_id: PMID:20668654
      supporting_text: Structure of the CaMKIIdelta/calmodulin complex reveals the
        molecular mechanism of CaMKII kinase activation.
- term:
    id: GO:0044325
    label: transmembrane transporter binding
  evidence_type: IPI
  original_reference_id: PMID:21167176
  review:
    summary: CALM1 binds IQ motif of cardiac sodium channel NaV1.5 for regulation.
    action: ACCEPT
    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.
    supported_by:
    - reference_id: PMID:21167176
      supporting_text: Solution NMR structure of Apo-calmodulin in complex with the
        IQ motif of human cardiac sodium channel NaV1.5
- term:
    id: GO:0044325
    label: transmembrane transporter binding
  evidence_type: IPI
  original_reference_id: PMID:23040497
  review:
    summary: Reactome pathway annotation - see individual pathways for specific functions
    action: ACCEPT
    reason: TAS evidence from curated Reactome pathways. These annotations reflect
      the diverse cellular processes involving CALM1.
    supported_by:
    - reference_id: PMID:23040497
      supporting_text: Mutations in calmodulin cause ventricular tachycardia and sudden
        cardiac death.
- term:
    id: GO:0051592
    label: response to calcium ion
  evidence_type: IDA
  original_reference_id: PMID:7607248
  review:
    summary: CALM1 responds to calcium through conformational change and target binding.
    action: ACCEPT
    reason: IDA evidence shows calcium-dependent response through titin kinase binding.
      Core mechanism of CALM1 function.
    supported_by:
    - reference_id: PMID:7607248
      supporting_text: A calmodulin-binding sequence in the C-terminus of human cardiac
        titin kinase
- term:
    id: GO:0055117
    label: regulation of cardiac muscle contraction
  evidence_type: IMP
  original_reference_id: PMID:23040497
  review:
    summary: Reactome pathway annotation - see individual pathways for specific functions
    action: ACCEPT
    reason: TAS evidence from curated Reactome pathways. These annotations reflect
      the diverse cellular processes involving CALM1.
    supported_by:
    - reference_id: PMID:23040497
      supporting_text: Mutations in calmodulin cause ventricular tachycardia and sudden
        cardiac death.
- term:
    id: GO:0072542
    label: protein phosphatase activator activity
  evidence_type: IDA
  original_reference_id: PMID:8631777
  review:
    summary: Reactome pathway annotation - see individual pathways for specific functions
    action: ACCEPT
    reason: TAS evidence from curated Reactome pathways. These annotations reflect
      the diverse cellular processes involving CALM1.
    supported_by:
    - reference_id: PMID:8631777
      supporting_text: Blocking the Ca2+-induced conformational transitions in calmodulin
        with disulfide bonds.
- term:
    id: GO:0005509
    label: calcium ion binding
  evidence_type: IDA
  original_reference_id: PMID:26164367
  review:
    summary: Duplicate with IDA evidence from RyR2 arrhythmia study.
    action: ACCEPT
    reason: Core function studied in context of calmodulin mutations and RyR2-mediated
      disease.
    supported_by:
    - reference_id: PMID:26164367
      supporting_text: Distinctive malfunctions of calmodulin mutations associated
        with heart RyR2-mediated arrhythmic disease
- term:
    id: GO:0005509
    label: calcium ion binding
  evidence_type: IDA
  original_reference_id: PMID:26969752
  review:
    summary: Duplicate with IDA evidence from LQTS study.
    action: ACCEPT
    reason: Core function studied in Long QT syndrome mutations.
    supported_by:
    - reference_id: PMID:26969752
      supporting_text: Spectrum and Prevalence of CALM1-, CALM2-, and CALM3-Encoded
        Calmodulin Variants in Long QT Syndrome
- term:
    id: GO:0005509
    label: calcium ion binding
  evidence_type: IDA
  original_reference_id: PMID:27516456
  review:
    summary: Duplicate with IDA evidence from CPVT mutation study.
    action: ACCEPT
    reason: Core function studied in CPVT-associated CALM3-A103V mutation.
    supported_by:
    - reference_id: PMID:27516456
      supporting_text: Novel CPVT-Associated Calmodulin Mutation in CALM3 (CALM3-A103V)
        Activates Arrhythmogenic Ca Waves and Sparks
- term:
    id: GO:0005737
    label: cytoplasm
  evidence_type: IDA
  original_reference_id: PMID:27165696
  review:
    summary: Reactome pathway annotation - see individual pathways for specific functions
    action: ACCEPT
    reason: TAS evidence from curated Reactome pathways. These annotations reflect
      the diverse cellular processes involving CALM1.
    supported_by:
    - reference_id: PMID:27165696
      supporting_text: 2016 May 7. Arrhythmogenic calmodulin mutations impede activation
        of small-conductance calcium-activated potassium current.
- term:
    id: GO:0019855
    label: calcium channel inhibitor activity
  evidence_type: IDA
  original_reference_id: PMID:26969752
  review:
    summary: CALM1 inhibits calcium channels - mutations cause Long QT syndrome through
      loss of inhibition.
    action: ACCEPT
    reason: IDA evidence (PMID:26969752) from LQTS study shows CALM1 inhibits calcium
      channels. E141G mutation impairs this function causing LQTS. Important negative
      regulatory function.
    supported_by:
    - reference_id: PMID:26969752
      supporting_text: 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
- term:
    id: GO:0060314
    label: regulation of ryanodine-sensitive calcium-release channel activity
  evidence_type: IDA
  original_reference_id: PMID:22067155
  review:
    summary: Reactome pathway annotation - see individual pathways for specific functions
    action: ACCEPT
    reason: TAS evidence from curated Reactome pathways. These annotations reflect
      the diverse cellular processes involving CALM1.
    supported_by:
    - reference_id: PMID:22067155
      supporting_text: Nov 1. FRET detection of calmodulin binding to the cardiac
        RyR2 calcium release channel.
- term:
    id: GO:0060315
    label: negative regulation of ryanodine-sensitive calcium-release channel activity
  evidence_type: IDA
  original_reference_id: PMID:26164367
  review:
    summary: Core cardiac function - CALM1 negatively regulates RyR2 to prevent calcium
      leak and arrhythmias.
    action: ACCEPT
    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.
    supported_by:
    - reference_id: PMID:26164367
      supporting_text: Distinctive malfunctions of calmodulin mutations associated
        with heart RyR2-mediated arrhythmic disease
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:16127172
  review:
    summary: Reactome pathway annotation - see individual pathways for specific functions
    action: ACCEPT
    reason: TAS evidence from curated Reactome pathways. These annotations reflect
      the diverse cellular processes involving CALM1.
    supported_by:
    - reference_id: PMID:16127172
      supporting_text: 2005 Aug 26. Calcium/calmodulin regulates ubiquitination of
        the ubiquitin-specific protease TRE17/USP6.
- term:
    id: GO:0005509
    label: calcium ion binding
  evidence_type: IDA
  original_reference_id: PMID:27564677
  review:
    summary: Duplicate with IDA evidence from M-channel/KCNQ study.
    action: ACCEPT
    reason: Core function demonstrated in structural study of KCNQ channel regulation.
    supported_by:
    - reference_id: PMID:27564677
      supporting_text: Structural Insights into the M-Channel Proximal C-Terminus/Calmodulin
        Complex
core_functions:
- description: Binds calcium ions through four EF-hand domains enabling conformational
    changes that regulate calcium-dependent enzymes and signaling pathways
  molecular_function:
    id: GO:0005509
    label: calcium ion binding
  directly_involved_in:
  - id: GO:0005513
    label: detection of calcium ion
  - id: GO:0097720
    label: calcineurin-mediated signaling
  locations:
  - id: GO:0005737
    label: cytoplasm
  - id: GO:0005886
    label: plasma membrane
  supported_by:
  - reference_id: PMID:23040497
    supporting_text: Both CALM1 substitutions demonstrated compromised calcium binding
  - reference_id: PMID:31454269
    supporting_text: Calmodulin mutations are associated with a diversity of heart
      rhythm disorders, including LQTS, CPVT, idiopathic ventricular tachycardia,
      and sudden death
- description: Activates protein serine/threonine kinases including CaMKII in calcium-dependent
    manner
  molecular_function:
    id: GO:0043539
    label: protein serine/threonine kinase activator activity
  directly_involved_in:
  - id: GO:0046427
    label: positive regulation of receptor signaling pathway via JAK-STAT
  - id: GO:0035458
    label: cellular response to interferon-beta
  - id: GO:0060291
    label: long-term synaptic potentiation
  locations:
  - id: GO:0005737
    label: cytoplasm
  supported_by:
  - reference_id: PMID:35568036
    supporting_text: A family of conserved bacterial virulence factors dampens interferon
      responses by blocking calcium signaling
  - reference_id: PMID:14722083
    supporting_text: Comparative analyses of the three-dimensional structures and
      enzymatic properties of alpha, beta, gamma and delta isoforms of Ca2+-calmodulin-dependent
      protein kinase II
- description: Activates calcineurin phosphatase in calcium-dependent manner to dephosphorylate
    substrates including NFAT transcription factors
  molecular_function:
    id: GO:0072542
    label: protein phosphatase activator activity
  directly_involved_in:
  - id: GO:0097720
    label: calcineurin-mediated signaling
  locations:
  - id: GO:0005737
    label: cytoplasm
  - id: GO:0005829
    label: cytosol
  supported_by:
  - reference_id: PMID:8631777
    supporting_text: Blocking the Ca2+-induced conformational transitions in calmodulin
      with disulfide bonds
- description: Regulates cardiac and skeletal muscle calcium channels including ryanodine
    receptor RyR2 and L-type calcium channels to control calcium release and excitation-contraction
    coupling
  molecular_function:
    id: GO:0005246
    label: calcium channel regulator activity
  directly_involved_in:
  - id: GO:0010880
    label: regulation of release of sequestered calcium ion into cytosol by sarcoplasmic
      reticulum
  - id: GO:0010881
    label: regulation of cardiac muscle contraction by regulation of the release of
      sequestered calcium ion
  - id: GO:1901844
    label: regulation of cell communication by electrical coupling involved in cardiac
      conduction
  - id: GO:0002027
    label: regulation of heart rate
  locations:
  - id: GO:0030017
    label: sarcomere
  anatomical_locations:
  - id: UBERON:0000948
    label: heart
  - id: UBERON:0001134
    label: skeletal muscle tissue
  supported_by:
  - reference_id: PMID:20226167
    supporting_text: Defective calmodulin binding to the cardiac ryanodine receptor
      plays a key role in CPVT-associated channel dysfunction
  - reference_id: PMID:23040497
    supporting_text: Mutations in calmodulin cause ventricular tachycardia and sudden
      cardiac death
  in_complex:
    id: GO:0034704
    label: calcium channel complex
- description: Activates adenylate cyclase in calcium-dependent manner for cAMP signaling
  molecular_function:
    id: GO:0010856
    label: adenylate cyclase activator activity
  directly_involved_in:
  - id: GO:0007186
    label: G protein-coupled receptor signaling pathway
  locations:
  - id: GO:0005737
    label: cytoplasm
  supported_by:
  - reference_id: PMID:11807546
    supporting_text: Structural basis for the activation of anthrax adenylyl cyclase
      exotoxin by calmodulin
  in_complex:
    id: GO:1902494
    label: catalytic complex
- description: Regulates cytokinesis through calcium-dependent interaction with centrosomal
    protein CP110
  molecular_function:
    id: GO:0048306
    label: calcium-dependent protein binding
  directly_involved_in:
  - id: GO:0032465
    label: regulation of cytokinesis
  - id: GO:0000086
    label: G2/M transition of mitotic cell cycle
  locations:
  - id: GO:0005813
    label: centrosome
  - id: GO:0000922
    label: spindle pole
  - id: GO:0005876
    label: spindle microtubule
  supported_by:
  - reference_id: PMID:16760425
    supporting_text: CP110 cooperates with two calcium-binding proteins to regulate
      cytokinesis and genome stability
references:
- id: GO_REF:0000033
  title: Annotation inferences using phylogenetic trees
  findings: []
- id: GO_REF:0000043
  title: Gene Ontology annotation based on UniProtKB/Swiss-Prot keyword mapping
  findings: []
- id: GO_REF:0000044
  title: Gene Ontology annotation based on UniProtKB/Swiss-Prot Subcellular Location
    vocabulary mapping, accompanied by conservative changes to GO terms applied by
    UniProt.
  findings: []
- id: GO_REF:0000107
  title: Automatic transfer of experimentally verified manual GO annotation data to
    orthologs using Ensembl Compara.
  findings: []
- id: GO_REF:0000117
  title: Electronic Gene Ontology annotations created by ARBA machine learning models
  findings: []
- id: GO_REF:0000120
  title: Combined Automated Annotation using Multiple IEA Methods.
  findings: []
- id: PMID:10692436
  title: Ca(2+)-dependent and Ca(2+)-independent calmodulin binding sites in erythrocyte
    protein 4.1. Implications for regulation of protein 4.1 interactions with transmembrane
    proteins.
  findings: []
- id: PMID:10899953
  title: Calmodulin regulation of basal and agonist-stimulated G protein coupling
    by the mu-opioid receptor (OP(3)) in morphine-pretreated cell.
  findings: []
- id: PMID:11807546
  title: Structural basis for the activation of anthrax adenylyl cyclase exotoxin
    by calmodulin.
  findings: []
- id: PMID:11972023
  title: Requirement of Ca2+ and CaMKII for Stat1 Ser-727 phosphorylation in response
    to IFN-gamma.
  findings: []
- id: PMID:11984006
  title: The Chediak-Higashi protein interacts with SNARE complex and signal transduction
    proteins.
  findings: []
- id: PMID:14722083
  title: Comparative analyses of the three-dimensional structures and enzymatic properties
    of alpha, beta, gamma and delta isoforms of Ca2+-calmodulin-dependent protein
    kinase II.
  findings: []
- id: PMID:15140941
  title: Ca2+-binding protein-1 facilitates and forms a postsynaptic complex with
    Cav1.2 (L-type) Ca2+ channels.
  findings: []
- id: PMID:15632291
  title: Myristoyl moiety of HIV Nef is involved in regulation of the interaction
    with calmodulin in vivo.
  findings: []
- id: PMID:16127172
  title: Calcium/calmodulin regulates ubiquitination of the ubiquitin-specific protease
    TRE17/USP6.
  findings: []
- id: PMID:16760425
  title: CP110 cooperates with two calcium-binding proteins to regulate cytokinesis
    and genome stability.
  findings: []
- id: PMID:19190083
  title: 'Characterization of exosome-like vesicles released from human tracheobronchial
    ciliated epithelium: a possible role in innate defense.'
  findings: []
- id: PMID:19855925
  title: Structural analysis of the complex between calmodulin and full-length myelin
    basic protein, an intrinsically disordered molecule.
  findings: []
- id: PMID:20226167
  title: Defective calmodulin binding to the cardiac ryanodine receptor plays a key
    role in CPVT-associated channel dysfunction.
  findings: []
- id: PMID:20668654
  title: Structure of the CaMKIIdelta/calmodulin complex reveals the molecular mechanism
    of CaMKII kinase activation.
  findings: []
- id: PMID:21167176
  title: Solution NMR structure of Apo-calmodulin in complex with the IQ motif of
    human cardiac sodium channel NaV1.5.
  findings: []
- id: PMID:21299499
  title: 'IQ-motif selectivity in human IQGAP2 and IQGAP3: binding of calmodulin and
    myosin essential light chain.'
  findings: []
- id: PMID:21630459
  title: Proteomic characterization of the human sperm nucleus.
  findings: []
- id: PMID:22067155
  title: FRET detection of calmodulin binding to the cardiac RyR2 calcium release
    channel.
  findings: []
- id: PMID:22926577
  title: Quantitative proteomic analysis of human substantia nigra in Alzheimer's
    disease, Huntington's disease and Multiple sclerosis.
  findings: []
- id: PMID:23040497
  title: Mutations in calmodulin cause ventricular tachycardia and sudden cardiac
    death.
  findings: []
- id: PMID:26164367
  title: Distinctive malfunctions of calmodulin mutations associated with heart RyR2-mediated
    arrhythmic disease.
  findings: []
- id: PMID:26969752
  title: 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.
  findings: []
- id: PMID:27165696
  title: Arrhythmogenic calmodulin mutations impede activation of small-conductance
    calcium-activated potassium current.
  findings: []
- id: PMID:27516456
  title: Novel CPVT-Associated Calmodulin Mutation in CALM3 (CALM3-A103V) Activates
    Arrhythmogenic Ca Waves and Sparks.
  findings: []
- id: PMID:27564677
  title: Structural Insights into the M-Channel Proximal C-Terminus/Calmodulin Complex.
  findings: []
- id: PMID:28890335
  title: The ER-Localized Transmembrane Protein EPG-3/VMP1 Regulates SERCA Activity
    to Control ER-Isolation Membrane Contacts for Autophagosome Formation.
  findings: []
- id: PMID:30021165
  title: 'Regulation of KIF1A-Driven Dense Core Vesicle Transport: Ca(2+)/CaM Controls
    DCV Binding and Liprin-α/TANC2 Recruits DCVs to Postsynaptic Sites.'
  findings: []
- id: PMID:30287853
  title: Calcineurin B homologous protein 3 binds with high affinity to the CHP binding
    domain of the human sodium/proton exchanger NHE1.
  findings: []
- id: PMID:30842726
  title: An IQSEC2 Mutation Associated With Intellectual Disability and Autism Results
    in Decreased Surface AMPA Receptors.
  findings: []
- id: PMID:3111527
  title: 'Comparison of S100b protein with calmodulin: interactions with melittin
    and microtubule-associated tau proteins and inhibition of phosphorylation of tau
    proteins by protein kinase C.'
  findings: []
- id: PMID:31454269
  title: Genetic Mosaicism in Calmodulinopathy.
  findings: []
- id: PMID:31983428
  title: Interaction between IDH1 WT and calmodulin and its implications for glioblastoma
    cell growth and migration.
  findings: []
- id: PMID:35271311
  title: 'OpenCell: Endogenous tagging for the cartography of human cellular organization.'
  findings: []
- id: PMID:35568036
  title: A family of conserved bacterial virulence factors dampens interferon responses
    by blocking calcium signaling.
  findings: []
- id: PMID:7607248
  title: A calmodulin-binding sequence in the C-terminus of human cardiac titin kinase.
  findings: []
- id: PMID:8631777
  title: Blocking the Ca2+-induced conformational transitions in calmodulin with disulfide
    bonds.
  findings: []
- id: Reactome:R-HSA-111915
  title: CAMK4 autophosphorylates
  findings: []
- id: Reactome:R-HSA-111966
  title: GRK2 binds CALM1:4Ca2+
  findings: []
- id: Reactome:R-HSA-1497784
  title: The cofactor BH4 is required for electron transfer in the eNOS catalytic
    cycle
  findings: []
- id: Reactome:R-HSA-1497796
  title: BH2 binding can lead to eNOS uncoupling
  findings: []
- id: Reactome:R-HSA-1497810
  title: Uncoupled eNOS favours the formation of superoxide
  findings: []
- id: Reactome:R-HSA-1855153
  title: I(1,4,5)P3 is phosphorylated to I(1,3,4,5)P4 by ITPKA/B/C in the cytosol
  findings: []
- id: Reactome:R-HSA-202110
  title: eNOS:Caveolin-1 complex binds to CaM
  findings: []
- id: Reactome:R-HSA-202111
  title: AKT1 phosphorylates eNOS
  findings: []
- id: Reactome:R-HSA-202127
  title: eNOS synthesizes NO
  findings: []
- id: Reactome:R-HSA-202129
  title: HSP90 binds eNOS:Caveolin-1:CaM complex
  findings: []
- id: Reactome:R-HSA-202137
  title: AKT1 binds eNOS complex via HSP90
  findings: []
- id: Reactome:R-HSA-202144
  title: Caveolin-1 dissociates from eNOS:CaM:HSP90 complex
  findings: []
- id: Reactome:R-HSA-2025890
  title: Calcineurin binds NFATC1,2,3
  findings: []
- id: Reactome:R-HSA-2730849
  title: Calcineurin binds and dephosphorylates NFAT
  findings: []
- id: Reactome:R-HSA-2730867
  title: Translocation of CaN:CaM:NFAT to nucleus
  findings: []
- id: Reactome:R-HSA-2730872
  title: Activation of Calcineurin
  findings: []
- id: Reactome:R-HSA-3229181
  title: CALM1:Ca2+ binds CNG channel
  findings: []
- id: Reactome:R-HSA-4332358
  title: Dissociation of CaM and CAMK2 autophosphorylation
  findings: []
- id: Reactome:R-HSA-4332359
  title: Active calmodulin binds CAMK2
  findings: []
- id: Reactome:R-HSA-4332363
  title: Autophosphorylation and activation of CAMK2
  findings: []
- id: Reactome:R-HSA-442749
  title: CaMKK autophosphorylates in the nucleus
  findings: []
- id: Reactome:R-HSA-445797
  title: MYLK (MLCK) Active Calmodulin Binding
  findings: []
- id: Reactome:R-HSA-445813
  title: Phosphorylation of Smooth Muscle Myosin Light Chains
  findings: []
- id: Reactome:R-HSA-451283
  title: kainate receptor binds glutamate
  findings: []
- id: Reactome:R-HSA-451311
  title: Activation of Ca-permeable Kainate receptors
  findings: []
- id: Reactome:R-HSA-4551451
  title: Calcineurin binds and dephosphorylates NFAT1 in response to WNT/Ca2+ signaling
  findings: []
- id: Reactome:R-HSA-4551465
  title: Translocation of NFATC1:CaN:CaM to nucleus
  findings: []
- id: Reactome:R-HSA-482772
  title: Release of platelet cytosolic components
  findings: []
- id: Reactome:R-HSA-5626549
  title: IQGAPs bind CALM1
  findings: []
- id: Reactome:R-HSA-5672965
  title: RAS GEFs promote RAS nucleotide exchange
  findings: []
- id: Reactome:R-HSA-6786205
  title: KAMKMT transfers 3xCH3 groups from 3xAdoMet to CALM1
  findings: []
- id: Reactome:R-HSA-71541
  title: glycogen phosphorylase (PYGM) dimer b + 2 ATP => glycogen phosphorylase (PYGM)
    dimer a + 2 ADP
  findings: []
- id: Reactome:R-HSA-71588
  title: glycogen phosphorylase (PYGL) dimer b + 2 ATP => glycogen phosphorylase (PYGL)
    dimer a + 2 ADP
  findings: []
- id: Reactome:R-HSA-9618785
  title: Calmodulin binds neurogranin
  findings: []
- id: Reactome:R-HSA-9619355
  title: CaMKK autophosphorylates in the cytosol
  findings: []
- id: Reactome:R-HSA-9619376
  title: CAMK1 binds calmodulin
  findings: []
- id: Reactome:R-HSA-9653585
  title: S-Farn-Me KRAS4B binds calmodulin
  findings: []
- id: Reactome:R-HSA-9654521
  title: Calmodulin dissociates KRAS4B from the plasma membrane
  findings: []
- id: Reactome:R-HSA-9654523
  title: ARL2:GTP bind PDE6D on KRAS4B
  findings: []
- id: Reactome:R-HSA-9654525
  title: PDE6D binds S-Farn-Me KRAS4B:CALM:4 Ca2+
  findings: []
- id: Reactome:R-HSA-9654533
  title: KRAS4B recycles to the plasma membrane
  findings: []
- id: Reactome:R-HSA-9865670
  title: TRPV4 tetramer binds CALM1:Ca2+ (calmodulin:Ca2+)
  findings: []
- id: Reactome:R-NUL-9617449
  title: Rasgrf1 promotes activation of HRAS
  findings: []
- id: Reactome:R-NUL-9618916
  title: Camkk1 binds activated calmodulin in the nucleus
  findings: []
- id: Reactome:R-NUL-9619177
  title: Camkk2 phosphorylates CAMK4
  findings: []
- id: Reactome:R-NUL-9619243
  title: Camkk1 binds activated calmodulin in the cytosol
  findings: []
- id: Reactome:R-NUL-9619396
  title: CAMKK1 phosphorylates CAMK1
  findings: []
- id: Reactome:R-NUL-9619413
  title: CAMKK2 phosphorylates Camk1
  findings: []
- id: file:human/CALM1/CALM1-deep-research-falcon.md
  title: Deep research on CALM1 function
  findings: []
status: COMPLETE