CALM3

UniProt ID: P0DP25
Organism: Homo sapiens
Review Status: COMPLETE
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Gene Description

CALM3 encodes one of the three human calmodulin genes and produces the same 149 aa calmodulin protein encoded by CALM1 and CALM2. The protein is a ubiquitous calcium sensor with four EF-hand motifs that binds calcium and regulates ion channels, protein kinases, protein phosphatases, and cell-division machinery. For this review, annotations were interpreted at the protein level: core calcium-sensing functions transfer well across the calmodulin family because the encoded protein sequence is identical, whereas tissue-specific neuronal, cardiac, and subcellular-context terms are kept as non-core when they likely reflect expression or recruitment differences rather than a CALM3-specific biochemical difference. CALM3 variants contribute to calmodulinopathy, including CPVT and long-QT phenotypes driven by dysregulated calcium-channel signaling.

Existing Annotations Review

GO Term Evidence Action Reason
GO:0005737 cytoplasm
IBA
GO_REF:0000033 		ACCEPT
Summary: Primary cytoplasmic localization
Reason: Core calmodulin function or localization
GO:0005509 calcium ion binding
IBA
GO_REF:0000033 		ACCEPT
Summary: Core calcium-binding function through 4 EF-hand domains
Reason: Core calmodulin function or localization
GO:0005634 nucleus
IBA
GO_REF:0000033 		KEEP AS NON CORE
Summary: Nuclear localization in some contexts
Reason: Tissue-specific or specialized function
GO:0010880 regulation of release of sequestered calcium ion into cytosol by sarcoplasmic reticulum
IBA
GO_REF:0000033 		ACCEPT
Summary: Regulates RyR-mediated calcium release from SR
Reason: Core calmodulin function or localization
GO:0005513 detection of calcium ion
IBA
GO_REF:0000033 		ACCEPT
Summary: Core calcium sensing function
Reason: Core calmodulin function or localization
GO:0097720 calcineurin-mediated signaling
IBA
GO_REF:0000033 		ACCEPT
Summary: Activates calcineurin phosphatase for NFAT signaling
Reason: Core calmodulin function or localization
GO:0005813 centrosome
IBA
GO_REF:0000033 		ACCEPT
Summary: Centrosomal localization for cell division
Reason: Core calmodulin function or localization
GO:0043209 myelin sheath
IBA
GO_REF:0000033 		KEEP AS NON CORE
Summary: Myelin sheath localization
Reason: Tissue-specific or specialized function
GO:0000922 spindle pole
IEA
GO_REF:0000120 		ACCEPT
Summary: Spindle pole localization during mitosis
Reason: Core calmodulin function or localization
GO:0002027 regulation of heart rate
IEA
GO_REF:0000117 		ACCEPT
Summary: Heart rate regulation through ion channel modulation
Reason: Core calmodulin function or localization
GO:0005246 calcium channel regulator activity
IEA
GO_REF:0000117 		ACCEPT
Summary: Regulates L-type calcium channels and ryanodine receptors
Reason: Core calmodulin function or localization
GO:0005509 calcium ion binding
IEA
GO_REF:0000120 		ACCEPT
Summary: Core calcium-binding function through 4 EF-hand domains
Reason: Core calmodulin function or localization
GO:0005513 detection of calcium ion
IEA
GO_REF:0000117 		ACCEPT
Summary: Core calcium sensing function
Reason: Core calmodulin function or localization
GO:0005813 centrosome
IEA
GO_REF:0000120 		ACCEPT
Summary: Centrosomal localization for cell division
Reason: Core calmodulin function or localization
GO:0005819 spindle
IEA
GO_REF:0000044 		ACCEPT
Summary: Spindle localization for cell division
Reason: Core calmodulin function or localization
GO:0005876 spindle microtubule
IEA
GO_REF:0000117 		ACCEPT
Summary: Spindle microtubule association
Reason: Core calmodulin function or localization
GO:0010856 adenylate cyclase activator activity
IEA
GO_REF:0000117 		ACCEPT
Summary: Activates adenylate cyclase for cAMP signaling
Reason: Core calmodulin function or localization
GO:0010881 regulation of cardiac muscle contraction by regulation of the release of sequestered calcium ion
IEA
GO_REF:0000117 		ACCEPT
Summary: Cardiac calcium-induced calcium release regulation
Reason: Core calmodulin function or localization
GO:0019901 protein kinase binding
IEA
GO_REF:0000117 		ACCEPT
Summary: Binds CaMK family and other protein kinases
Reason: Core calmodulin function or localization
GO:0030017 sarcomere
IEA
GO_REF:0000117 		KEEP AS NON CORE
Summary: Sarcomere localization in muscle
Reason: Tissue-specific or specialized function
GO:0031432 titin binding
IEA
GO_REF:0000117 		KEEP AS NON CORE
Summary: Titin binding in muscle
Reason: Tissue-specific or specialized function
GO:0032465 regulation of cytokinesis
IEA
GO_REF:0000117 		ACCEPT
Summary: Cytokinesis regulation with CP110 and centrin
Reason: Core calmodulin function or localization
GO:0034704 calcium channel complex
IEA
GO_REF:0000117 		ACCEPT
Summary: Component of calcium channel complexes
Reason: Core calmodulin function or localization
GO:0043539 protein serine/threonine kinase activator activity
IEA
GO_REF:0000117 		ACCEPT
Summary: Activates CaMKII and other calcium-dependent kinases
Reason: Core calmodulin function or localization
GO:0060291 long-term synaptic potentiation
IEA
GO_REF:0000117 		KEEP AS NON CORE
Summary: Long-term synaptic potentiation reflects specialized neuronal signaling.
Reason: Calmodulin is important for synaptic plasticity, but this is a tissue-specific downstream context and should not be used to distinguish CALM3 from CALM1 or CALM2.
GO:0072542 protein phosphatase activator activity
IEA
GO_REF:0000117 		ACCEPT
Summary: Activates calcineurin (PP2B) phosphatase
Reason: Core calmodulin function or localization
GO:0097720 calcineurin-mediated signaling
IEA
GO_REF:0000117 		ACCEPT
Summary: Activates calcineurin phosphatase for NFAT signaling
Reason: Core calmodulin function or localization
GO:1901844 regulation of cell communication by electrical coupling involved in cardiac conduction
IEA
GO_REF:0000117 		KEEP AS NON CORE
Summary: Cardiac electrical coupling regulation
Reason: Tissue-specific or specialized function
GO:0005515 protein binding
IPI
PMID:35271311
OpenCell: Endogenous tagging for the cartography of human ce... 		MARK AS OVER ANNOTATED
Summary: Too general - more specific terms available
Reason: Too general - more specific terms are available
GO:0000785 chromatin
IEA
GO_REF:0000120 		KEEP AS NON CORE
Summary: Chromatin association
Reason: Tissue-specific or specialized function
GO:0001975 response to amphetamine
IEA
GO_REF:0000120 		KEEP AS NON CORE
Summary: Amphetamine response in neurons
Reason: Tissue-specific or specialized function
GO:0005634 nucleus
IEA
GO_REF:0000120 		KEEP AS NON CORE
Summary: Nuclear localization in some contexts
Reason: Tissue-specific or specialized function
GO:0008076 voltage-gated potassium channel complex
IEA
GO_REF:0000120 		KEEP AS NON CORE
Summary: KCNQ channel complex component
Reason: Tissue-specific or specialized function
GO:0016020 membrane
IEA
GO_REF:0000107 		KEEP AS NON CORE
Summary: General membrane localization is plausible but not a core assignment.
Reason: Calmodulin is recruited to membrane-associated channels and receptors, but broad membrane localization is secondary to its core soluble calcium-sensor role.
GO:0019904 protein domain specific binding
IEA
GO_REF:0000120 		KEEP AS NON CORE
Summary: IQ motif and calmodulin-binding domain recognition
Reason: Tissue-specific or specialized function
GO:0030235 nitric-oxide synthase regulator activity
IEA
GO_REF:0000120 		ACCEPT
Summary: Regulates NOS enzymes
Reason: Core calmodulin function or localization
GO:0030426 growth cone
IEA
GO_REF:0000120 		KEEP AS NON CORE
Summary: Neuronal growth cone localization
Reason: Tissue-specific or specialized function
GO:0030672 synaptic vesicle membrane
IEA
GO_REF:0000120 		KEEP AS NON CORE
Summary: Synaptic vesicle localization
Reason: Tissue-specific or specialized function
GO:0031800 type 3 metabotropic glutamate receptor binding
IEA
GO_REF:0000120 		KEEP AS NON CORE
Summary: mGluR3 binding in neurons
Reason: Tissue-specific or specialized function
GO:0031966 mitochondrial membrane
IEA
GO_REF:0000120 		KEEP AS NON CORE
Summary: Mitochondrial membrane association
Reason: Tissue-specific or specialized function
GO:0031982 vesicle
IEA
GO_REF:0000107 		KEEP AS NON CORE
Summary: Vesicle association is observed in specialized trafficking or exosome contexts.
Reason: Vesicle localization reflects specific cell-type and trafficking contexts rather than a defining family-wide localization for the identical calmodulin protein.
GO:0043209 myelin sheath
IEA
GO_REF:0000120 		KEEP AS NON CORE
Summary: Myelin sheath localization
Reason: Tissue-specific or specialized function
GO:0043548 phosphatidylinositol 3-kinase binding
IEA
GO_REF:0000120 		KEEP AS NON CORE
Summary: PI3K binding for signaling
Reason: Tissue-specific or specialized function
GO:0044305 calyx of Held
IEA
GO_REF:0000120 		KEEP AS NON CORE
Summary: Calyx of Held synapse localization
Reason: Tissue-specific or specialized function
GO:0044325 transmembrane transporter binding
IEA
GO_REF:0000120 		ACCEPT
Summary: Binds ion channels and transporters
Reason: Core calmodulin function or localization
GO:0048306 calcium-dependent protein binding
IEA
GO_REF:0000120 		ACCEPT
Summary: Calcium-dependent target protein binding
Reason: Core calmodulin function or localization
GO:0050998 nitric-oxide synthase binding
IEA
GO_REF:0000120 		ACCEPT
Summary: Binds NOS for activation
Reason: Core calmodulin function or localization
GO:0051412 response to corticosterone
IEA
GO_REF:0000120 		KEEP AS NON CORE
Summary: Corticosterone response
Reason: Tissue-specific or specialized function
GO:0097225 sperm midpiece
IEA
GO_REF:0000107 		KEEP AS NON CORE
Summary: Sperm midpiece localization
Reason: Tissue-specific or specialized function
GO:0098685 Schaffer collateral - CA1 synapse
IEA
GO_REF:0000120 		KEEP AS NON CORE
Summary: Hippocampal synapse localization
Reason: Tissue-specific or specialized function
GO:0099523 presynaptic cytosol
IEA
GO_REF:0000120 		KEEP AS NON CORE
Summary: Presynaptic localization
Reason: Tissue-specific or specialized function
GO:0099524 postsynaptic cytosol
IEA
GO_REF:0000120 		KEEP AS NON CORE
Summary: Postsynaptic localization
Reason: Tissue-specific or specialized function
GO:0140238 presynaptic endocytosis
IEA
GO_REF:0000120 		KEEP AS NON CORE
Summary: Presynaptic vesicle endocytosis
Reason: Tissue-specific or specialized function
GO:0141110 transporter inhibitor activity
IEA
GO_REF:0000107 		MARK AS OVER ANNOTATED
Summary: This term is too specific for the available transfer evidence.
Reason: Calmodulin modulates multiple transporters and channels, but a generic transporter inhibitor term overstates a context-dependent regulatory effect.
GO:1900242 regulation of synaptic vesicle endocytosis
IEA
GO_REF:0000120 		KEEP AS NON CORE
Summary: Synaptic vesicle endocytosis regulation
Reason: Tissue-specific or specialized function
GO:1905913 negative regulation of calcium ion export across plasma membrane
IEA
GO_REF:0000107 		KEEP AS NON CORE
Summary: Negative regulation of calcium export is plausible in channel-regulatory contexts but not a core assignment.
Reason: This term reflects a specific downstream physiological setting of calmodulin-dependent channel regulation rather than a defining family-wide process.
GO:2000300 regulation of synaptic vesicle exocytosis
IEA
GO_REF:0000120 		KEEP AS NON CORE
Summary: Synaptic vesicle exocytosis regulation
Reason: Tissue-specific or specialized function
GO:0005829 cytosol
TAS
Reactome:R-HSA-9956602 		ACCEPT
Summary: Soluble cytosolic protein
Reason: Core calmodulin function or localization
GO:0005829 cytosol
TAS
Reactome:R-HSA-9956624 		ACCEPT
Summary: Soluble cytosolic protein
Reason: Core calmodulin function or localization
GO:0005829 cytosol
TAS
Reactome:R-HSA-9956667 		ACCEPT
Summary: Soluble cytosolic protein
Reason: Core calmodulin function or localization
GO:0010881 regulation of cardiac muscle contraction by regulation of the release of sequestered calcium ion
IDA
PMID:23040497
Mutations in calmodulin cause ventricular tachycardia and su... 		ACCEPT
Summary: Cardiac calcium-induced calcium release regulation
Reason: Core calmodulin function or localization
GO:1901844 regulation of cell communication by electrical coupling involved in cardiac conduction
IDA
PMID:23040497
Mutations in calmodulin cause ventricular tachycardia and su... 		KEEP AS NON CORE
Summary: Cardiac electrical coupling regulation
Reason: Tissue-specific or specialized function
GO:0005246 calcium channel regulator activity
IDA
PMID:20226167
Defective calmodulin binding to the cardiac ryanodine recept... 		ACCEPT
Summary: Regulates L-type calcium channels and ryanodine receptors
Reason: Core calmodulin function or localization
GO:0010881 regulation of cardiac muscle contraction by regulation of the release of sequestered calcium ion
IDA
PMID:20226167
Defective calmodulin binding to the cardiac ryanodine recept... 		ACCEPT
Summary: Cardiac calcium-induced calcium release regulation
Reason: Core calmodulin function or localization
GO:0060291 long-term synaptic potentiation
TAS
PMID:20668654
Structure of the CaMKIIdelta/calmodulin complex reveals the ... 		KEEP AS NON CORE
Summary: Long-term synaptic potentiation reflects specialized neuronal signaling.
Reason: Calmodulin is important for synaptic plasticity, but this is a tissue-specific downstream context and should not be used to distinguish CALM3 from CALM1 or CALM2.
GO:0097720 calcineurin-mediated signaling
IDA
PMID:8631777
Blocking the Ca2+-induced conformational transitions in calm... 		ACCEPT
Summary: Activates calcineurin phosphatase for NFAT signaling
Reason: Core calmodulin function or localization
GO:0005515 protein binding
IPI
PMID:11984006
The Chediak-Higashi protein interacts with SNARE complex and... 		MARK AS OVER ANNOTATED
Summary: Too general - more specific terms available
Reason: Too general - more specific terms are available
GO:0005515 protein binding
IPI
PMID:19855925
Structural analysis of the complex between calmodulin and fu... 		MARK AS OVER ANNOTATED
Summary: Too general - more specific terms available
Reason: Too general - more specific terms are available
GO:0005509 calcium ion binding
IDA
PMID:35568036
A family of conserved bacterial virulence factors dampens in... 		ACCEPT
Summary: Core calcium-binding function through 4 EF-hand domains
Reason: Core calmodulin function or localization
GO:0043539 protein serine/threonine kinase activator activity
IDA
PMID:35568036
A family of conserved bacterial virulence factors dampens in... 		ACCEPT
Summary: Activates CaMKII and other calcium-dependent kinases
Reason: Core calmodulin function or localization
GO:0005509 calcium ion binding
IDA
PMID:31454269
Genetic Mosaicism in Calmodulinopathy. 		ACCEPT
Summary: Core calcium-binding function through 4 EF-hand domains
Reason: Core calmodulin function or localization
GO:0098901 regulation of cardiac muscle cell action potential
IMP
PMID:31454269
Genetic Mosaicism in Calmodulinopathy. 		KEEP AS NON CORE
Summary: Cardiac action potential regulation
Reason: Tissue-specific or specialized function
GO:1901842 negative regulation of high voltage-gated calcium channel activity
IMP
PMID:31454269
Genetic Mosaicism in Calmodulinopathy. 		KEEP AS NON CORE
Summary: Calcium channel activity regulation
Reason: Tissue-specific or specialized function
GO:0010856 adenylate cyclase activator activity
IDA
PMID:11807546
Structural basis for the activation of anthrax adenylyl cycl... 		ACCEPT
Summary: Activates adenylate cyclase for cAMP signaling
Reason: Core calmodulin function or localization
GO:0034704 calcium channel complex
IDA
PMID:23040497
Mutations in calmodulin cause ventricular tachycardia and su... 		ACCEPT
Summary: Component of calcium channel complexes
Reason: Core calmodulin function or localization
GO:0000922 spindle pole
IDA
PMID:16760425
CP110 cooperates with two calcium-binding proteins to regula... 		ACCEPT
Summary: Spindle pole localization during mitosis
Reason: Core calmodulin function or localization
GO:0005515 protein binding
IPI
PMID:10692436
Ca(2+)-dependent and Ca(2+)-independent calmodulin binding s... 		MARK AS OVER ANNOTATED
Summary: Too general - more specific terms available
Reason: Too general - more specific terms are available
GO:0005515 protein binding
IPI
PMID:15140941
Ca2+-binding protein-1 facilitates and forms a postsynaptic ... 		MARK AS OVER ANNOTATED
Summary: Too general - more specific terms available
Reason: Too general - more specific terms are available
GO:0005515 protein binding
IPI
PMID:15632291
Myristoyl moiety of HIV Nef is involved in regulation of the... 		MARK AS OVER ANNOTATED
Summary: Too general - more specific terms available
Reason: Too general - more specific terms are available
GO:0005515 protein binding
IPI
PMID:16760425
CP110 cooperates with two calcium-binding proteins to regula... 		MARK AS OVER ANNOTATED
Summary: Too general - more specific terms available
Reason: Too general - more specific terms are available
GO:0005515 protein binding
IPI
PMID:21299499
IQ-motif selectivity in human IQGAP2 and IQGAP3: binding of ... 		MARK AS OVER ANNOTATED
Summary: Too general - more specific terms available
Reason: Too general - more specific terms are available
GO:0005515 protein binding
IPI
PMID:3111527
Comparison of S100b protein with calmodulin: interactions wi... 		MARK AS OVER ANNOTATED
Summary: Too general - more specific terms available
Reason: Too general - more specific terms are available
GO:0005634 nucleus
HDA
PMID:21630459
Proteomic characterization of the human sperm nucleus. 		KEEP AS NON CORE
Summary: Nuclear localization in some contexts
Reason: Tissue-specific or specialized function
GO:0005737 cytoplasm
TAS
PMID:10899953
Calmodulin regulation of basal and agonist-stimulated G prot... 		ACCEPT
Summary: Primary cytoplasmic localization
Reason: Core calmodulin function or localization
GO:0005813 centrosome
IDA
PMID:16760425
CP110 cooperates with two calcium-binding proteins to regula... 		ACCEPT
Summary: Centrosomal localization for cell division
Reason: Core calmodulin function or localization
GO:0005876 spindle microtubule
IDA
PMID:16760425
CP110 cooperates with two calcium-binding proteins to regula... 		ACCEPT
Summary: Spindle microtubule association
Reason: Core calmodulin function or localization
GO:0005886 plasma membrane
TAS
PMID:10899953
Calmodulin regulation of basal and agonist-stimulated G prot... 		KEEP AS NON CORE
Summary: Plasma membrane association occurs in specific signaling contexts.
Reason: Calmodulin can associate with membrane-proximal receptor and channel complexes, but plasma membrane residence is context dependent rather than a defining family-wide localization.
GO:0007186 G protein-coupled receptor signaling pathway
TAS
PMID:10899953
Calmodulin regulation of basal and agonist-stimulated G prot... 		KEEP AS NON CORE
Summary: Calmodulin modulates selected GPCR signaling pathways in specialized contexts.
Reason: This captures a real signaling interaction, but the evidence is receptor- and context-specific and should not be treated as a defining CALM3 function relative to the other calmodulin paralogs.
GO:0021762 substantia nigra development
HEP
PMID:22926577
Quantitative proteomic analysis of human substantia nigra in... 		REMOVE
Summary: Proteomic detection in substantia nigra does not justify a developmental annotation.
Reason: The cited evidence is expression/proteomics in diseased tissue, not functional evidence for substantia nigra development.
GO:0031982 vesicle
HDA
PMID:19190083
Characterization of exosome-like vesicles released from huma... 		KEEP AS NON CORE
Summary: Vesicle association is observed in specialized trafficking or exosome contexts.
Reason: Vesicle localization reflects specific cell-type and trafficking contexts rather than a defining family-wide localization for the identical calmodulin protein.
GO:0032465 regulation of cytokinesis
IMP
PMID:16760425
CP110 cooperates with two calcium-binding proteins to regula... 		ACCEPT
Summary: Cytokinesis regulation with CP110 and centrin
Reason: Core calmodulin function or localization
GO:0005509 calcium ion binding
IDA
PMID:11807546
Structural basis for the activation of anthrax adenylyl cycl... 		ACCEPT
Summary: Core calcium-binding function through 4 EF-hand domains
Reason: Core calmodulin function or localization
GO:0008179 adenylate cyclase binding
IPI
PMID:11807546
Structural basis for the activation of anthrax adenylyl cycl... 		KEEP AS NON CORE
Summary: Direct adenylate cyclase binding is supported, but mainly in host-pathogen interaction studies.
Reason: The interaction is real biochemistry for calmodulin, but the cited evidence centers on bacterial edema-factor activation rather than a defining endogenous CALM3 role.
GO:0032991 protein-containing complex
IDA
PMID:19855925
Structural analysis of the complex between calmodulin and fu... 		MARK AS OVER ANNOTATED
Summary: Too general - more specific terms available
Reason: Too general - more specific terms are available
GO:1902494 catalytic complex
IDA
PMID:11807546
Structural basis for the activation of anthrax adenylyl cycl... 		KEEP AS NON CORE
Summary: Part of enzyme complexes
Reason: Tissue-specific or specialized function
GO:0002027 regulation of heart rate
IMP
PMID:23040497
Mutations in calmodulin cause ventricular tachycardia and su... 		ACCEPT
Summary: Heart rate regulation through ion channel modulation
Reason: Core calmodulin function or localization
GO:0005509 calcium ion binding
IDA
PMID:23040497
Mutations in calmodulin cause ventricular tachycardia and su... 		ACCEPT
Summary: Core calcium-binding function through 4 EF-hand domains
Reason: Core calmodulin function or localization
GO:0005509 calcium ion binding
IDA
PMID:7607248
A calmodulin-binding sequence in the C-terminus of human car... 		ACCEPT
Summary: Core calcium-binding function through 4 EF-hand domains
Reason: Core calmodulin function or localization
GO:0005509 calcium ion binding
IDA
PMID:8631777
Blocking the Ca2+-induced conformational transitions in calm... 		ACCEPT
Summary: Core calcium-binding function through 4 EF-hand domains
Reason: Core calmodulin function or localization
GO:0005513 detection of calcium ion
IMP
PMID:23040497
Mutations in calmodulin cause ventricular tachycardia and su... 		ACCEPT
Summary: Core calcium sensing function
Reason: Core calmodulin function or localization
GO:0010880 regulation of release of sequestered calcium ion into cytosol by sarcoplasmic reticulum
IDA
PMID:20226167
Defective calmodulin binding to the cardiac ryanodine recept... 		ACCEPT
Summary: Regulates RyR-mediated calcium release from SR
Reason: Core calmodulin function or localization
GO:0019901 protein kinase binding
IPI
PMID:20668654
Structure of the CaMKIIdelta/calmodulin complex reveals the ... 		ACCEPT
Summary: Binds CaMK family and other protein kinases
Reason: Core calmodulin function or localization
GO:0030017 sarcomere
IDA
PMID:20226167
Defective calmodulin binding to the cardiac ryanodine recept... 		KEEP AS NON CORE
Summary: Sarcomere localization in muscle
Reason: Tissue-specific or specialized function
GO:0031432 titin binding
IPI
PMID:7607248
A calmodulin-binding sequence in the C-terminus of human car... 		KEEP AS NON CORE
Summary: Titin binding in muscle
Reason: Tissue-specific or specialized function
GO:0043539 protein serine/threonine kinase activator activity
TAS
PMID:20668654
Structure of the CaMKIIdelta/calmodulin complex reveals the ... 		ACCEPT
Summary: Activates CaMKII and other calcium-dependent kinases
Reason: Core calmodulin function or localization
GO:0044325 transmembrane transporter binding
IPI
PMID:21167176
Solution NMR structure of Apo-calmodulin in complex with the... 		ACCEPT
Summary: Binds ion channels and transporters
Reason: Core calmodulin function or localization
GO:0044325 transmembrane transporter binding
IPI
PMID:23040497
Mutations in calmodulin cause ventricular tachycardia and su... 		ACCEPT
Summary: Binds ion channels and transporters
Reason: Core calmodulin function or localization
GO:0051592 response to calcium ion
IDA
PMID:7607248
A calmodulin-binding sequence in the C-terminus of human car... 		KEEP AS NON CORE
Summary: Response to calcium ion
Reason: Tissue-specific or specialized function
GO:0055117 regulation of cardiac muscle contraction
IMP
PMID:23040497
Mutations in calmodulin cause ventricular tachycardia and su... 		ACCEPT
Summary: Cardiac contraction through calcium channel regulation
Reason: Core calmodulin function or localization
GO:0072542 protein phosphatase activator activity
IDA
PMID:8631777
Blocking the Ca2+-induced conformational transitions in calm... 		ACCEPT
Summary: Activates calcineurin (PP2B) phosphatase
Reason: Core calmodulin function or localization
GO:0005509 calcium ion binding
IDA
PMID:27516456
Novel CPVT-Associated Calmodulin Mutation in CALM3 (CALM3-A1... 		ACCEPT
Summary: Core calcium-binding function through 4 EF-hand domains
Reason: Core calmodulin function or localization

Core Functions

Primary intracellular calcium sensor. CALM3-encoded calmodulin binds calcium through four EF-hand motifs and converts calcium fluctuations into target-protein regulation.

Molecular Function:
calcium ion binding
Directly Involved In:
detection of calcium ion
Cellular Locations:
cytoplasm
Supporting Evidence:
  • PMID:27516456
    Humans have 3 CaM genes ( CALM1 , CALM2 , and CALM3 ) encoding for a perfectly conserved sequence of amino acids
  • PMID:23040497
    Both CALM1 substitutions demonstrated compromised calcium binding

Core calcium-dependent signal-transduction adaptor for kinase and phosphatase regulation, especially CaMK and calcineurin pathways.

Molecular Function:
protein serine/threonine kinase activator activity
Directly Involved In:
calcineurin-mediated signaling
Cellular Locations:
cytoplasm
Supporting Evidence:
  • PMID:20668654
    Structure of the CaMKIIdelta/calmodulin complex reveals the molecular mechanism of CaMKII kinase activation.
  • PMID:35568036
    IFN inhibition was mediated by the binding of OspC1 and OspC3 to the Ca2+ sensor calmodulin (CaM), blocking CaM kinase II
  • PMID:8631777
    Blocking the Ca2+-induced conformational transitions in calmodulin with disulfide bonds.

Regulator of cardiac and other excitable-cell calcium channels, especially RyR2 and high-voltage-gated calcium-channel pathways.

Molecular Function:
calcium channel regulator activity
Directly Involved In:
regulation of release of sequestered calcium ion into cytosol by sarcoplasmic reticulum
Cellular Locations:
cytoplasm
Supporting Evidence:
  • PMID:20226167
    the addition of a high concentration of CaM attenuated the aberrant increase of Ca(2+) sparks
  • PMID:27516456
    A103V-CaM (100 nmol/L) promoted spontaneous Ca wave and spark activity
  • PMID:31454269
    Human-induced pluripotent stem cell-derived cardiomyocytes overexpressing mutant or wild-type CaM showed that both mutants impaired Ca2+-dependent inactivation of L-type Ca2+ channels and prolonged action potential duration

Centrosome-associated regulator of late cytokinesis through CP110/centrin-containing cell-division machinery.

Molecular Function:
protein kinase binding
Directly Involved In:
regulation of cytokinesis
Cellular Locations:
centrosome spindle pole
Supporting Evidence:
  • PMID:16760425
    its depletion leads to a failure at a late stage of cytokinesis and the formation of binucleate cells

References

GO_REF:0000033
Annotation inferences using phylogenetic trees
GO_REF:0000044
Gene Ontology annotation based on UniProtKB/Swiss-Prot Subcellular Location vocabulary mapping, accompanied by conservative changes to GO terms applied by UniProt
GO_REF:0000107
Automatic transfer of experimentally verified manual GO annotation data to orthologs using Ensembl Compara
GO_REF:0000117
Electronic Gene Ontology annotations created by ARBA machine learning models
GO_REF:0000120
Combined Automated Annotation using Multiple IEA Methods
PMID:10692436
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.
PMID:10899953
Calmodulin regulation of basal and agonist-stimulated G protein coupling by the mu-opioid receptor (OP(3)) in morphine-pretreated cell.
PMID:11807546
Structural basis for the activation of anthrax adenylyl cyclase exotoxin by calmodulin.
PMID:11984006
The Chediak-Higashi protein interacts with SNARE complex and signal transduction proteins.
PMID:15140941
Ca2+-binding protein-1 facilitates and forms a postsynaptic complex with Cav1.2 (L-type) Ca2+ channels.
PMID:15632291
Myristoyl moiety of HIV Nef is involved in regulation of the interaction with calmodulin in vivo.
PMID:16760425
CP110 cooperates with two calcium-binding proteins to regulate cytokinesis and genome stability.
PMID:19190083
Characterization of exosome-like vesicles released from human tracheobronchial ciliated epithelium: a possible role in innate defense.
PMID:19855925
Structural analysis of the complex between calmodulin and full-length myelin basic protein, an intrinsically disordered molecule.
PMID:20226167
Defective calmodulin binding to the cardiac ryanodine receptor plays a key role in CPVT-associated channel dysfunction.
PMID:20668654
Structure of the CaMKIIdelta/calmodulin complex reveals the molecular mechanism of CaMKII kinase activation.
PMID:21167176
Solution NMR structure of Apo-calmodulin in complex with the IQ motif of human cardiac sodium channel NaV1.5.
PMID:21299499
IQ-motif selectivity in human IQGAP2 and IQGAP3: binding of calmodulin and myosin essential light chain.
PMID:21630459
Proteomic characterization of the human sperm nucleus.
PMID:22926577
Quantitative proteomic analysis of human substantia nigra in Alzheimer's disease, Huntington's disease and Multiple sclerosis.
PMID:23040497
Mutations in calmodulin cause ventricular tachycardia and sudden cardiac death.
PMID:27516456
Novel CPVT-Associated Calmodulin Mutation in CALM3 (CALM3-A103V) Activates Arrhythmogenic Ca Waves and Sparks.
PMID:3111527
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.
PMID:31454269
Genetic Mosaicism in Calmodulinopathy.
PMID:35271311
OpenCell: Endogenous tagging for the cartography of human cellular organization.
PMID:35568036
A family of conserved bacterial virulence factors dampens interferon responses by blocking calcium signaling.
PMID:7607248
A calmodulin-binding sequence in the C-terminus of human cardiac titin kinase.
PMID:8631777
Blocking the Ca2+-induced conformational transitions in calmodulin with disulfide bonds.
Reactome:R-HSA-9956602
CALM binds bacterial OspC3
Reactome:R-HSA-9956624
OspC3 ADP-riboxanates CASP4
Reactome:R-HSA-9956667
CASP4 binds CALM:OspC3
PMID:9681195
Characterization of the human CALM2 calmodulin gene and comparison of the transcriptional activity of CALM1, CALM2 and CALM3.
file:human/CALM3/CALM3-notes.md
Curator notes for CALM3 review

📚 Additional Documentation

Notes

(CALM3-notes.md)

CALM3 notes

2026-03-19

  • Review scope: the CALM3 GOA file fetched on 2026-03-19 contains no literal ISO evidence-code rows, but it does contain multiple transferred annotations (IBA and IEA). I reviewed those in the spirit of [projects/ISO.md] by asking whether a term is safe to transfer across the human calmodulin paralogs.
  • Family identity: humans have three calmodulin genes, CALM1, CALM2, and CALM3, and all three encode an identical 149 aa calmodulin polypeptide PMID:27516456 PMID:31454269.
  • Family regulation differs even when protein sequence does not: transcription of the three genes is not equivalent, and in teratoma cells CALM3 was reported to be more highly transcribed than CALM1 or CALM2 PMID:9681195.
  • Curation consequence: core protein-level functions that follow directly from the conserved calmodulin sequence are safe to treat as family-wide, especially calcium binding, calcium sensing, kinase/phosphatase activation, and ion-channel regulation PMID:27516456 PMID:23040497.
  • Cardiac core function is strong for the protein family and directly relevant to CALM3: defective calmodulin regulation of RyR2 increases spontaneous calcium release events PMID:20226167 and the CALM3 A103V mutation promotes arrhythmogenic calcium waves and sparks PMID:27516456.
  • CALM3 also has direct human disease evidence for impaired L-type calcium channel regulation and action potential phenotypes in calmodulinopathy PMID:31454269.
  • Cell-division localization/function is supported independently of cardiac biology: calmodulin binds CP110 and loss of that interaction disrupts late cytokinesis PMID:16760425.
  • Microbial hijacking papers support genuine calmodulin biochemistry but not necessarily core host biological-process terms. OspC-family effectors bind calmodulin and block CaMKII / IFN signaling PMID:35568036, but those infection-context processes should stay non-core.
  • Several GOA terms are too context-specific to distinguish CALM3 from CALM1 / CALM2: synaptic localizations, myelin-associated terms, sperm terms, and specialized membrane-trafficking terms likely reflect cell-type context layered on top of the same calmodulin protein sequence rather than a CALM3-specific biochemical innovation PMID:9681195.
  • Some annotations should be removed or down-weighted on evidence quality grounds. substantia nigra development is based on proteomic detection in diseased tissue rather than developmental perturbation PMID:22926577.
  • Generic protein binding annotations are not informative for calmodulin and should not be favored when more specific regulator/binding terms are available.
  • Current UniProt entries for CALM1, CALM2, and CALM3 all show the same 149 aa sequence summary and I found no ALTERNATIVE PRODUCTS block in these local records, so there is no isoform-specific caveat comparable to the splice-isoform project genes [file:human/CALM1/CALM1-uniprot.txt "SQ SEQUENCE 149 AA"] [file:human/CALM2/CALM2-uniprot.txt "SQ SEQUENCE 149 AA"] [file:human/CALM3/CALM3-uniprot.txt "SQ SEQUENCE 149 AA"].

📄 View Raw YAML

 
id: P0DP25
gene_symbol: CALM3
product_type: PROTEIN
status: COMPLETE
taxon:
  id: NCBITaxon:9606
  label: Homo sapiens
description: 'CALM3 encodes one of the three human calmodulin genes and produces the
  same 149 aa calmodulin protein encoded by CALM1 and CALM2. The protein is a ubiquitous
  calcium sensor with four EF-hand motifs that binds calcium and regulates ion channels,
  protein kinases, protein phosphatases, and cell-division machinery. For this review,
  annotations were interpreted at the protein level: core calcium-sensing functions
  transfer well across the calmodulin family because the encoded protein sequence
  is identical, whereas tissue-specific neuronal, cardiac, and subcellular-context
  terms are kept as non-core when they likely reflect expression or recruitment differences
  rather than a CALM3-specific biochemical difference. CALM3 variants contribute to
  calmodulinopathy, including CPVT and long-QT phenotypes driven by dysregulated calcium-channel
  signaling.'
existing_annotations:
- term:
    id: GO:0005737
    label: cytoplasm
  evidence_type: IBA
  original_reference_id: GO_REF:0000033
  review:
    summary: Primary cytoplasmic localization
    action: ACCEPT
    reason: Core calmodulin function or localization
- term:
    id: GO:0005509
    label: calcium ion binding
  evidence_type: IBA
  original_reference_id: GO_REF:0000033
  review:
    summary: Core calcium-binding function through 4 EF-hand domains
    action: ACCEPT
    reason: Core calmodulin function or localization
- term:
    id: GO:0005634
    label: nucleus
  evidence_type: IBA
  original_reference_id: GO_REF:0000033
  review:
    summary: Nuclear localization in some contexts
    action: KEEP_AS_NON_CORE
    reason: Tissue-specific or specialized function
- 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: Regulates RyR-mediated calcium release from SR
    action: ACCEPT
    reason: Core calmodulin function or localization
- term:
    id: GO:0005513
    label: detection of calcium ion
  evidence_type: IBA
  original_reference_id: GO_REF:0000033
  review:
    summary: Core calcium sensing function
    action: ACCEPT
    reason: Core calmodulin function or localization
- term:
    id: GO:0097720
    label: calcineurin-mediated signaling
  evidence_type: IBA
  original_reference_id: GO_REF:0000033
  review:
    summary: Activates calcineurin phosphatase for NFAT signaling
    action: ACCEPT
    reason: Core calmodulin function or localization
- term:
    id: GO:0005813
    label: centrosome
  evidence_type: IBA
  original_reference_id: GO_REF:0000033
  review:
    summary: Centrosomal localization for cell division
    action: ACCEPT
    reason: Core calmodulin function or localization
- term:
    id: GO:0043209
    label: myelin sheath
  evidence_type: IBA
  original_reference_id: GO_REF:0000033
  review:
    summary: Myelin sheath localization
    action: KEEP_AS_NON_CORE
    reason: Tissue-specific or specialized function
- term:
    id: GO:0000922
    label: spindle pole
  evidence_type: IEA
  original_reference_id: GO_REF:0000120
  review:
    summary: Spindle pole localization during mitosis
    action: ACCEPT
    reason: Core calmodulin function or localization
- term:
    id: GO:0002027
    label: regulation of heart rate
  evidence_type: IEA
  original_reference_id: GO_REF:0000117
  review:
    summary: Heart rate regulation through ion channel modulation
    action: ACCEPT
    reason: Core calmodulin function or localization
- term:
    id: GO:0005246
    label: calcium channel regulator activity
  evidence_type: IEA
  original_reference_id: GO_REF:0000117
  review:
    summary: Regulates L-type calcium channels and ryanodine receptors
    action: ACCEPT
    reason: Core calmodulin function or localization
- term:
    id: GO:0005509
    label: calcium ion binding
  evidence_type: IEA
  original_reference_id: GO_REF:0000120
  review:
    summary: Core calcium-binding function through 4 EF-hand domains
    action: ACCEPT
    reason: Core calmodulin function or localization
- term:
    id: GO:0005513
    label: detection of calcium ion
  evidence_type: IEA
  original_reference_id: GO_REF:0000117
  review:
    summary: Core calcium sensing function
    action: ACCEPT
    reason: Core calmodulin function or localization
- term:
    id: GO:0005813
    label: centrosome
  evidence_type: IEA
  original_reference_id: GO_REF:0000120
  review:
    summary: Centrosomal localization for cell division
    action: ACCEPT
    reason: Core calmodulin function or localization
- term:
    id: GO:0005819
    label: spindle
  evidence_type: IEA
  original_reference_id: GO_REF:0000044
  review:
    summary: Spindle localization for cell division
    action: ACCEPT
    reason: Core calmodulin function or localization
- term:
    id: GO:0005876
    label: spindle microtubule
  evidence_type: IEA
  original_reference_id: GO_REF:0000117
  review:
    summary: Spindle microtubule association
    action: ACCEPT
    reason: Core calmodulin function or localization
- term:
    id: GO:0010856
    label: adenylate cyclase activator activity
  evidence_type: IEA
  original_reference_id: GO_REF:0000117
  review:
    summary: Activates adenylate cyclase for cAMP signaling
    action: ACCEPT
    reason: Core calmodulin function or localization
- 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: Cardiac calcium-induced calcium release regulation
    action: ACCEPT
    reason: Core calmodulin function or localization
- term:
    id: GO:0019901
    label: protein kinase binding
  evidence_type: IEA
  original_reference_id: GO_REF:0000117
  review:
    summary: Binds CaMK family and other protein kinases
    action: ACCEPT
    reason: Core calmodulin function or localization
- term:
    id: GO:0030017
    label: sarcomere
  evidence_type: IEA
  original_reference_id: GO_REF:0000117
  review:
    summary: Sarcomere localization in muscle
    action: KEEP_AS_NON_CORE
    reason: Tissue-specific or specialized function
- term:
    id: GO:0031432
    label: titin binding
  evidence_type: IEA
  original_reference_id: GO_REF:0000117
  review:
    summary: Titin binding in muscle
    action: KEEP_AS_NON_CORE
    reason: Tissue-specific or specialized function
- term:
    id: GO:0032465
    label: regulation of cytokinesis
  evidence_type: IEA
  original_reference_id: GO_REF:0000117
  review:
    summary: Cytokinesis regulation with CP110 and centrin
    action: ACCEPT
    reason: Core calmodulin function or localization
- term:
    id: GO:0034704
    label: calcium channel complex
  evidence_type: IEA
  original_reference_id: GO_REF:0000117
  review:
    summary: Component of calcium channel complexes
    action: ACCEPT
    reason: Core calmodulin function or localization
- term:
    id: GO:0043539
    label: protein serine/threonine kinase activator activity
  evidence_type: IEA
  original_reference_id: GO_REF:0000117
  review:
    summary: Activates CaMKII and other calcium-dependent kinases
    action: ACCEPT
    reason: Core calmodulin function or localization
- term:
    id: GO:0060291
    label: long-term synaptic potentiation
  evidence_type: IEA
  original_reference_id: GO_REF:0000117
  review:
    summary: Long-term synaptic potentiation reflects specialized neuronal signaling.
    action: KEEP_AS_NON_CORE
    reason: Calmodulin is important for synaptic plasticity, but this is a tissue-specific
      downstream context and should not be used to distinguish CALM3 from CALM1 or
      CALM2.
- term:
    id: GO:0072542
    label: protein phosphatase activator activity
  evidence_type: IEA
  original_reference_id: GO_REF:0000117
  review:
    summary: Activates calcineurin (PP2B) phosphatase
    action: ACCEPT
    reason: Core calmodulin function or localization
- term:
    id: GO:0097720
    label: calcineurin-mediated signaling
  evidence_type: IEA
  original_reference_id: GO_REF:0000117
  review:
    summary: Activates calcineurin phosphatase for NFAT signaling
    action: ACCEPT
    reason: Core calmodulin function or localization
- 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: Cardiac electrical coupling regulation
    action: KEEP_AS_NON_CORE
    reason: Tissue-specific or specialized function
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:35271311
  review:
    summary: Too general - more specific terms available
    action: MARK_AS_OVER_ANNOTATED
    reason: Too general - more specific terms are available
- term:
    id: GO:0000785
    label: chromatin
  evidence_type: IEA
  original_reference_id: GO_REF:0000120
  review:
    summary: Chromatin association
    action: KEEP_AS_NON_CORE
    reason: Tissue-specific or specialized function
- term:
    id: GO:0001975
    label: response to amphetamine
  evidence_type: IEA
  original_reference_id: GO_REF:0000120
  review:
    summary: Amphetamine response in neurons
    action: KEEP_AS_NON_CORE
    reason: Tissue-specific or specialized function
- term:
    id: GO:0005634
    label: nucleus
  evidence_type: IEA
  original_reference_id: GO_REF:0000120
  review:
    summary: Nuclear localization in some contexts
    action: KEEP_AS_NON_CORE
    reason: Tissue-specific or specialized function
- term:
    id: GO:0008076
    label: voltage-gated potassium channel complex
  evidence_type: IEA
  original_reference_id: GO_REF:0000120
  review:
    summary: KCNQ channel complex component
    action: KEEP_AS_NON_CORE
    reason: Tissue-specific or specialized function
- term:
    id: GO:0016020
    label: membrane
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  review:
    summary: General membrane localization is plausible but not a core assignment.
    action: KEEP_AS_NON_CORE
    reason: Calmodulin is recruited to membrane-associated channels and receptors,
      but broad membrane localization is secondary to its core soluble calcium-sensor
      role.
- term:
    id: GO:0019904
    label: protein domain specific binding
  evidence_type: IEA
  original_reference_id: GO_REF:0000120
  review:
    summary: IQ motif and calmodulin-binding domain recognition
    action: KEEP_AS_NON_CORE
    reason: Tissue-specific or specialized function
- term:
    id: GO:0030235
    label: nitric-oxide synthase regulator activity
  evidence_type: IEA
  original_reference_id: GO_REF:0000120
  review:
    summary: Regulates NOS enzymes
    action: ACCEPT
    reason: Core calmodulin function or localization
- term:
    id: GO:0030426
    label: growth cone
  evidence_type: IEA
  original_reference_id: GO_REF:0000120
  review:
    summary: Neuronal growth cone localization
    action: KEEP_AS_NON_CORE
    reason: Tissue-specific or specialized function
- term:
    id: GO:0030672
    label: synaptic vesicle membrane
  evidence_type: IEA
  original_reference_id: GO_REF:0000120
  review:
    summary: Synaptic vesicle localization
    action: KEEP_AS_NON_CORE
    reason: Tissue-specific or specialized function
- term:
    id: GO:0031800
    label: type 3 metabotropic glutamate receptor binding
  evidence_type: IEA
  original_reference_id: GO_REF:0000120
  review:
    summary: mGluR3 binding in neurons
    action: KEEP_AS_NON_CORE
    reason: Tissue-specific or specialized function
- term:
    id: GO:0031966
    label: mitochondrial membrane
  evidence_type: IEA
  original_reference_id: GO_REF:0000120
  review:
    summary: Mitochondrial membrane association
    action: KEEP_AS_NON_CORE
    reason: Tissue-specific or specialized function
- term:
    id: GO:0031982
    label: vesicle
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  review:
    summary: Vesicle association is observed in specialized trafficking or exosome
      contexts.
    action: KEEP_AS_NON_CORE
    reason: Vesicle localization reflects specific cell-type and trafficking contexts
      rather than a defining family-wide localization for the identical calmodulin
      protein.
- term:
    id: GO:0043209
    label: myelin sheath
  evidence_type: IEA
  original_reference_id: GO_REF:0000120
  review:
    summary: Myelin sheath localization
    action: KEEP_AS_NON_CORE
    reason: Tissue-specific or specialized function
- term:
    id: GO:0043548
    label: phosphatidylinositol 3-kinase binding
  evidence_type: IEA
  original_reference_id: GO_REF:0000120
  review:
    summary: PI3K binding for signaling
    action: KEEP_AS_NON_CORE
    reason: Tissue-specific or specialized function
- term:
    id: GO:0044305
    label: calyx of Held
  evidence_type: IEA
  original_reference_id: GO_REF:0000120
  review:
    summary: Calyx of Held synapse localization
    action: KEEP_AS_NON_CORE
    reason: Tissue-specific or specialized function
- term:
    id: GO:0044325
    label: transmembrane transporter binding
  evidence_type: IEA
  original_reference_id: GO_REF:0000120
  review:
    summary: Binds ion channels and transporters
    action: ACCEPT
    reason: Core calmodulin function or localization
- term:
    id: GO:0048306
    label: calcium-dependent protein binding
  evidence_type: IEA
  original_reference_id: GO_REF:0000120
  review:
    summary: Calcium-dependent target protein binding
    action: ACCEPT
    reason: Core calmodulin function or localization
- term:
    id: GO:0050998
    label: nitric-oxide synthase binding
  evidence_type: IEA
  original_reference_id: GO_REF:0000120
  review:
    summary: Binds NOS for activation
    action: ACCEPT
    reason: Core calmodulin function or localization
- term:
    id: GO:0051412
    label: response to corticosterone
  evidence_type: IEA
  original_reference_id: GO_REF:0000120
  review:
    summary: Corticosterone response
    action: KEEP_AS_NON_CORE
    reason: Tissue-specific or specialized function
- term:
    id: GO:0097225
    label: sperm midpiece
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  review:
    summary: Sperm midpiece localization
    action: KEEP_AS_NON_CORE
    reason: Tissue-specific or specialized function
- term:
    id: GO:0098685
    label: Schaffer collateral - CA1 synapse
  evidence_type: IEA
  original_reference_id: GO_REF:0000120
  review:
    summary: Hippocampal synapse localization
    action: KEEP_AS_NON_CORE
    reason: Tissue-specific or specialized function
- term:
    id: GO:0099523
    label: presynaptic cytosol
  evidence_type: IEA
  original_reference_id: GO_REF:0000120
  review:
    summary: Presynaptic localization
    action: KEEP_AS_NON_CORE
    reason: Tissue-specific or specialized function
- term:
    id: GO:0099524
    label: postsynaptic cytosol
  evidence_type: IEA
  original_reference_id: GO_REF:0000120
  review:
    summary: Postsynaptic localization
    action: KEEP_AS_NON_CORE
    reason: Tissue-specific or specialized function
- term:
    id: GO:0140238
    label: presynaptic endocytosis
  evidence_type: IEA
  original_reference_id: GO_REF:0000120
  review:
    summary: Presynaptic vesicle endocytosis
    action: KEEP_AS_NON_CORE
    reason: Tissue-specific or specialized function
- term:
    id: GO:0141110
    label: transporter inhibitor activity
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  review:
    summary: This term is too specific for the available transfer evidence.
    action: MARK_AS_OVER_ANNOTATED
    reason: Calmodulin modulates multiple transporters and channels, but a generic
      transporter inhibitor term overstates a context-dependent regulatory effect.
- term:
    id: GO:1900242
    label: regulation of synaptic vesicle endocytosis
  evidence_type: IEA
  original_reference_id: GO_REF:0000120
  review:
    summary: Synaptic vesicle endocytosis regulation
    action: KEEP_AS_NON_CORE
    reason: Tissue-specific or specialized function
- 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: Negative regulation of calcium export is plausible in channel-regulatory
      contexts but not a core assignment.
    action: KEEP_AS_NON_CORE
    reason: This term reflects a specific downstream physiological setting of calmodulin-dependent
      channel regulation rather than a defining family-wide process.
- term:
    id: GO:2000300
    label: regulation of synaptic vesicle exocytosis
  evidence_type: IEA
  original_reference_id: GO_REF:0000120
  review:
    summary: Synaptic vesicle exocytosis regulation
    action: KEEP_AS_NON_CORE
    reason: Tissue-specific or specialized function
- term:
    id: GO:0005829
    label: cytosol
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-9956602
  review:
    summary: Soluble cytosolic protein
    action: ACCEPT
    reason: Core calmodulin function or localization
- term:
    id: GO:0005829
    label: cytosol
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-9956624
  review:
    summary: Soluble cytosolic protein
    action: ACCEPT
    reason: Core calmodulin function or localization
- term:
    id: GO:0005829
    label: cytosol
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-9956667
  review:
    summary: Soluble cytosolic protein
    action: ACCEPT
    reason: Core calmodulin function or localization
- 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: Cardiac calcium-induced calcium release regulation
    action: ACCEPT
    reason: Core calmodulin function or localization
- 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: Cardiac electrical coupling regulation
    action: KEEP_AS_NON_CORE
    reason: Tissue-specific or specialized function
- term:
    id: GO:0005246
    label: calcium channel regulator activity
  evidence_type: IDA
  original_reference_id: PMID:20226167
  review:
    summary: Regulates L-type calcium channels and ryanodine receptors
    action: ACCEPT
    reason: Core calmodulin function or localization
- 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: Cardiac calcium-induced calcium release regulation
    action: ACCEPT
    reason: Core calmodulin function or localization
- term:
    id: GO:0060291
    label: long-term synaptic potentiation
  evidence_type: TAS
  original_reference_id: PMID:20668654
  review:
    summary: Long-term synaptic potentiation reflects specialized neuronal signaling.
    action: KEEP_AS_NON_CORE
    reason: Calmodulin is important for synaptic plasticity, but this is a tissue-specific
      downstream context and should not be used to distinguish CALM3 from CALM1 or
      CALM2.
- term:
    id: GO:0097720
    label: calcineurin-mediated signaling
  evidence_type: IDA
  original_reference_id: PMID:8631777
  review:
    summary: Activates calcineurin phosphatase for NFAT signaling
    action: ACCEPT
    reason: Core calmodulin function or localization
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:11984006
  review:
    summary: Too general - more specific terms available
    action: MARK_AS_OVER_ANNOTATED
    reason: Too general - more specific terms are available
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:19855925
  review:
    summary: Too general - more specific terms available
    action: MARK_AS_OVER_ANNOTATED
    reason: Too general - more specific terms are available
- term:
    id: GO:0005509
    label: calcium ion binding
  evidence_type: IDA
  original_reference_id: PMID:35568036
  review:
    summary: Core calcium-binding function through 4 EF-hand domains
    action: ACCEPT
    reason: Core calmodulin function or localization
- term:
    id: GO:0043539
    label: protein serine/threonine kinase activator activity
  evidence_type: IDA
  original_reference_id: PMID:35568036
  review:
    summary: Activates CaMKII and other calcium-dependent kinases
    action: ACCEPT
    reason: Core calmodulin function or localization
- term:
    id: GO:0005509
    label: calcium ion binding
  evidence_type: IDA
  original_reference_id: PMID:31454269
  review:
    summary: Core calcium-binding function through 4 EF-hand domains
    action: ACCEPT
    reason: Core calmodulin function or localization
- term:
    id: GO:0098901
    label: regulation of cardiac muscle cell action potential
  evidence_type: IMP
  original_reference_id: PMID:31454269
  review:
    summary: Cardiac action potential regulation
    action: KEEP_AS_NON_CORE
    reason: Tissue-specific or specialized function
- term:
    id: GO:1901842
    label: negative regulation of high voltage-gated calcium channel activity
  evidence_type: IMP
  original_reference_id: PMID:31454269
  review:
    summary: Calcium channel activity regulation
    action: KEEP_AS_NON_CORE
    reason: Tissue-specific or specialized function
- term:
    id: GO:0010856
    label: adenylate cyclase activator activity
  evidence_type: IDA
  original_reference_id: PMID:11807546
  review:
    summary: Activates adenylate cyclase for cAMP signaling
    action: ACCEPT
    reason: Core calmodulin function or localization
- term:
    id: GO:0034704
    label: calcium channel complex
  evidence_type: IDA
  original_reference_id: PMID:23040497
  review:
    summary: Component of calcium channel complexes
    action: ACCEPT
    reason: Core calmodulin function or localization
- term:
    id: GO:0000922
    label: spindle pole
  evidence_type: IDA
  original_reference_id: PMID:16760425
  review:
    summary: Spindle pole localization during mitosis
    action: ACCEPT
    reason: Core calmodulin function or localization
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:10692436
  review:
    summary: Too general - more specific terms available
    action: MARK_AS_OVER_ANNOTATED
    reason: Too general - more specific terms are available
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:15140941
  review:
    summary: Too general - more specific terms available
    action: MARK_AS_OVER_ANNOTATED
    reason: Too general - more specific terms are available
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:15632291
  review:
    summary: Too general - more specific terms available
    action: MARK_AS_OVER_ANNOTATED
    reason: Too general - more specific terms are available
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:16760425
  review:
    summary: Too general - more specific terms available
    action: MARK_AS_OVER_ANNOTATED
    reason: Too general - more specific terms are available
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:21299499
  review:
    summary: Too general - more specific terms available
    action: MARK_AS_OVER_ANNOTATED
    reason: Too general - more specific terms are available
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:3111527
  review:
    summary: Too general - more specific terms available
    action: MARK_AS_OVER_ANNOTATED
    reason: Too general - more specific terms are available
- term:
    id: GO:0005634
    label: nucleus
  evidence_type: HDA
  original_reference_id: PMID:21630459
  review:
    summary: Nuclear localization in some contexts
    action: KEEP_AS_NON_CORE
    reason: Tissue-specific or specialized function
- term:
    id: GO:0005737
    label: cytoplasm
  evidence_type: TAS
  original_reference_id: PMID:10899953
  review:
    summary: Primary cytoplasmic localization
    action: ACCEPT
    reason: Core calmodulin function or localization
- term:
    id: GO:0005813
    label: centrosome
  evidence_type: IDA
  original_reference_id: PMID:16760425
  review:
    summary: Centrosomal localization for cell division
    action: ACCEPT
    reason: Core calmodulin function or localization
- term:
    id: GO:0005876
    label: spindle microtubule
  evidence_type: IDA
  original_reference_id: PMID:16760425
  review:
    summary: Spindle microtubule association
    action: ACCEPT
    reason: Core calmodulin function or localization
- term:
    id: GO:0005886
    label: plasma membrane
  evidence_type: TAS
  original_reference_id: PMID:10899953
  review:
    summary: Plasma membrane association occurs in specific signaling contexts.
    action: KEEP_AS_NON_CORE
    reason: Calmodulin can associate with membrane-proximal receptor and channel complexes,
      but plasma membrane residence is context dependent rather than a defining family-wide
      localization.
- term:
    id: GO:0007186
    label: G protein-coupled receptor signaling pathway
  evidence_type: TAS
  original_reference_id: PMID:10899953
  review:
    summary: Calmodulin modulates selected GPCR signaling pathways in specialized
      contexts.
    action: KEEP_AS_NON_CORE
    reason: This captures a real signaling interaction, but the evidence is receptor-
      and context-specific and should not be treated as a defining CALM3 function
      relative to the other calmodulin paralogs.
- term:
    id: GO:0021762
    label: substantia nigra development
  evidence_type: HEP
  original_reference_id: PMID:22926577
  review:
    summary: Proteomic detection in substantia nigra does not justify a developmental
      annotation.
    action: REMOVE
    reason: The cited evidence is expression/proteomics in diseased tissue, not functional
      evidence for substantia nigra development.
- term:
    id: GO:0031982
    label: vesicle
  evidence_type: HDA
  original_reference_id: PMID:19190083
  review:
    summary: Vesicle association is observed in specialized trafficking or exosome
      contexts.
    action: KEEP_AS_NON_CORE
    reason: Vesicle localization reflects specific cell-type and trafficking contexts
      rather than a defining family-wide localization for the identical calmodulin
      protein.
- term:
    id: GO:0032465
    label: regulation of cytokinesis
  evidence_type: IMP
  original_reference_id: PMID:16760425
  review:
    summary: Cytokinesis regulation with CP110 and centrin
    action: ACCEPT
    reason: Core calmodulin function or localization
- term:
    id: GO:0005509
    label: calcium ion binding
  evidence_type: IDA
  original_reference_id: PMID:11807546
  review:
    summary: Core calcium-binding function through 4 EF-hand domains
    action: ACCEPT
    reason: Core calmodulin function or localization
- term:
    id: GO:0008179
    label: adenylate cyclase binding
  evidence_type: IPI
  original_reference_id: PMID:11807546
  review:
    summary: Direct adenylate cyclase binding is supported, but mainly in host-pathogen
      interaction studies.
    action: KEEP_AS_NON_CORE
    reason: The interaction is real biochemistry for calmodulin, but the cited evidence
      centers on bacterial edema-factor activation rather than a defining endogenous
      CALM3 role.
- term:
    id: GO:0032991
    label: protein-containing complex
  evidence_type: IDA
  original_reference_id: PMID:19855925
  review:
    summary: Too general - more specific terms available
    action: MARK_AS_OVER_ANNOTATED
    reason: Too general - more specific terms are available
- term:
    id: GO:1902494
    label: catalytic complex
  evidence_type: IDA
  original_reference_id: PMID:11807546
  review:
    summary: Part of enzyme complexes
    action: KEEP_AS_NON_CORE
    reason: Tissue-specific or specialized function
- term:
    id: GO:0002027
    label: regulation of heart rate
  evidence_type: IMP
  original_reference_id: PMID:23040497
  review:
    summary: Heart rate regulation through ion channel modulation
    action: ACCEPT
    reason: Core calmodulin function or localization
- term:
    id: GO:0005509
    label: calcium ion binding
  evidence_type: IDA
  original_reference_id: PMID:23040497
  review:
    summary: Core calcium-binding function through 4 EF-hand domains
    action: ACCEPT
    reason: Core calmodulin function or localization
- term:
    id: GO:0005509
    label: calcium ion binding
  evidence_type: IDA
  original_reference_id: PMID:7607248
  review:
    summary: Core calcium-binding function through 4 EF-hand domains
    action: ACCEPT
    reason: Core calmodulin function or localization
- term:
    id: GO:0005509
    label: calcium ion binding
  evidence_type: IDA
  original_reference_id: PMID:8631777
  review:
    summary: Core calcium-binding function through 4 EF-hand domains
    action: ACCEPT
    reason: Core calmodulin function or localization
- term:
    id: GO:0005513
    label: detection of calcium ion
  evidence_type: IMP
  original_reference_id: PMID:23040497
  review:
    summary: Core calcium sensing function
    action: ACCEPT
    reason: Core calmodulin function or localization
- 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: Regulates RyR-mediated calcium release from SR
    action: ACCEPT
    reason: Core calmodulin function or localization
- term:
    id: GO:0019901
    label: protein kinase binding
  evidence_type: IPI
  original_reference_id: PMID:20668654
  review:
    summary: Binds CaMK family and other protein kinases
    action: ACCEPT
    reason: Core calmodulin function or localization
- term:
    id: GO:0030017
    label: sarcomere
  evidence_type: IDA
  original_reference_id: PMID:20226167
  review:
    summary: Sarcomere localization in muscle
    action: KEEP_AS_NON_CORE
    reason: Tissue-specific or specialized function
- term:
    id: GO:0031432
    label: titin binding
  evidence_type: IPI
  original_reference_id: PMID:7607248
  review:
    summary: Titin binding in muscle
    action: KEEP_AS_NON_CORE
    reason: Tissue-specific or specialized function
- term:
    id: GO:0043539
    label: protein serine/threonine kinase activator activity
  evidence_type: TAS
  original_reference_id: PMID:20668654
  review:
    summary: Activates CaMKII and other calcium-dependent kinases
    action: ACCEPT
    reason: Core calmodulin function or localization
- term:
    id: GO:0044325
    label: transmembrane transporter binding
  evidence_type: IPI
  original_reference_id: PMID:21167176
  review:
    summary: Binds ion channels and transporters
    action: ACCEPT
    reason: Core calmodulin function or localization
- term:
    id: GO:0044325
    label: transmembrane transporter binding
  evidence_type: IPI
  original_reference_id: PMID:23040497
  review:
    summary: Binds ion channels and transporters
    action: ACCEPT
    reason: Core calmodulin function or localization
- term:
    id: GO:0051592
    label: response to calcium ion
  evidence_type: IDA
  original_reference_id: PMID:7607248
  review:
    summary: Response to calcium ion
    action: KEEP_AS_NON_CORE
    reason: Tissue-specific or specialized function
- term:
    id: GO:0055117
    label: regulation of cardiac muscle contraction
  evidence_type: IMP
  original_reference_id: PMID:23040497
  review:
    summary: Cardiac contraction through calcium channel regulation
    action: ACCEPT
    reason: Core calmodulin function or localization
- term:
    id: GO:0072542
    label: protein phosphatase activator activity
  evidence_type: IDA
  original_reference_id: PMID:8631777
  review:
    summary: Activates calcineurin (PP2B) phosphatase
    action: ACCEPT
    reason: Core calmodulin function or localization
- term:
    id: GO:0005509
    label: calcium ion binding
  evidence_type: IDA
  original_reference_id: PMID:27516456
  review:
    summary: Core calcium-binding function through 4 EF-hand domains
    action: ACCEPT
    reason: Core calmodulin function or localization
references:
- id: GO_REF:0000033
  title: Annotation inferences using phylogenetic trees
  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:11984006
  title: The Chediak-Higashi protein interacts with SNARE complex and signal transduction
    proteins.
  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: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: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:27516456
  title: Novel CPVT-Associated Calmodulin Mutation in CALM3 (CALM3-A103V) Activates
    Arrhythmogenic Ca Waves and Sparks.
  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: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-9956602
  title: CALM binds bacterial OspC3
  findings: []
- id: Reactome:R-HSA-9956624
  title: OspC3 ADP-riboxanates CASP4
  findings: []
- id: Reactome:R-HSA-9956667
  title: CASP4 binds CALM:OspC3
  findings: []
- id: PMID:9681195
  title: Characterization of the human CALM2 calmodulin gene and comparison of the
    transcriptional activity of CALM1, CALM2 and CALM3.
  findings: []
- id: file:human/CALM3/CALM3-notes.md
  title: Curator notes for CALM3 review
  findings: []
core_functions:
- description: Primary intracellular calcium sensor. CALM3-encoded calmodulin binds
    calcium through four EF-hand motifs and converts calcium fluctuations into target-protein
    regulation.
  molecular_function:
    id: GO:0005509
    label: calcium ion binding
  locations:
  - id: GO:0005737
    label: cytoplasm
  directly_involved_in:
  - id: GO:0005513
    label: detection of calcium ion
  supported_by:
  - reference_id: PMID:27516456
    supporting_text: Humans have 3 CaM genes ( CALM1 , CALM2 , and CALM3 ) encoding
      for a perfectly conserved sequence of amino acids
  - reference_id: PMID:23040497
    supporting_text: Both CALM1 substitutions demonstrated compromised calcium binding
- description: Core calcium-dependent signal-transduction adaptor for kinase and phosphatase
    regulation, especially CaMK and calcineurin pathways.
  molecular_function:
    id: GO:0043539
    label: protein serine/threonine kinase activator activity
  locations:
  - id: GO:0005737
    label: cytoplasm
  directly_involved_in:
  - id: GO:0097720
    label: calcineurin-mediated signaling
  supported_by:
  - reference_id: PMID:20668654
    supporting_text: Structure of the CaMKIIdelta/calmodulin complex reveals the molecular
      mechanism of CaMKII kinase activation.
  - 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
  - reference_id: PMID:8631777
    supporting_text: Blocking the Ca2+-induced conformational transitions in calmodulin
      with disulfide bonds.
- description: Regulator of cardiac and other excitable-cell calcium channels, especially
    RyR2 and high-voltage-gated calcium-channel pathways.
  molecular_function:
    id: GO:0005246
    label: calcium channel regulator activity
  locations:
  - id: GO:0005737
    label: cytoplasm
  directly_involved_in:
  - id: GO:0010880
    label: regulation of release of sequestered calcium ion into cytosol by sarcoplasmic
      reticulum
  supported_by:
  - reference_id: PMID:20226167
    supporting_text: the addition of a high concentration of CaM attenuated the aberrant
      increase of Ca(2+) sparks
  - reference_id: PMID:27516456
    supporting_text: A103V-CaM (100 nmol/L) promoted spontaneous Ca wave and spark
      activity
  - reference_id: PMID:31454269
    supporting_text: Human-induced pluripotent stem cell-derived cardiomyocytes overexpressing
      mutant or wild-type CaM showed that both mutants impaired Ca2+-dependent inactivation
      of L-type Ca2+ channels and prolonged action potential duration
- description: Centrosome-associated regulator of late cytokinesis through CP110/centrin-containing
    cell-division machinery.
  molecular_function:
    id: GO:0019901
    label: protein kinase binding
  locations:
  - id: GO:0005813
    label: centrosome
  - id: GO:0000922
    label: spindle pole
  directly_involved_in:
  - id: GO:0032465
    label: regulation of cytokinesis
  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