Camk2a

UniProt ID: P11798
Organism: Mus musculus
Review Status: COMPLETE
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Gene Description

Calcium/calmodulin-dependent protein kinase type II alpha subunit (CaMKIIΞ±). Functions as a serine/threonine kinase activated by Ca2+/calmodulin binding. Autophosphorylation at Thr-286 confers constitutive Ca2+-independent activity. Critical for synaptic plasticity, learning, and memory in the brain. Regulates NMDA receptor signaling, AMPA receptor trafficking, and dendritic spine development. Also involved in neuronal migration, endocannabinoid signaling, and JAK-STAT pathway activation.

Existing Annotations Review

GO Term Evidence Action Reason
GO:0004683 calcium/calmodulin-dependent protein kinase activity
IBA
GO_REF:0000033
ACCEPT
Summary: Core kinase function
Reason: Essential CaMKII activity
Supporting Evidence:
UniProt:P11798
FUNCTION: Calcium/calmodulin-dependent protein kinase that functions autonomously after Ca(2+)/calmodulin-binding and autophosphorylation
GO:0005737 cytoplasm
IBA
GO_REF:0000033
KEEP AS NON CORE
Summary: cytoplasm
Reason: Specialized cellular process
Supporting Evidence:
UniProt:P11798
SUBCELLULAR LOCATION:
GO:0014069 postsynaptic density
IBA
GO_REF:0000033
ACCEPT
Summary: Synaptic/neuronal function
Reason: Essential for CaMKII function
Supporting Evidence:
UniProt:P11798
GO; GO:0014069; C:postsynaptic density; IDA:MGI.
GO:0048168 regulation of neuronal synaptic plasticity
IBA
GO_REF:0000033
ACCEPT
Summary: Synaptic/neuronal function
Reason: Essential for CaMKII function
Supporting Evidence:
UniProt:P11798
FUNCTION: Calcium/calmodulin-dependent protein kinase that functions autonomously after Ca(2+)/calmodulin-binding and autophosphorylation, and is involved in various processes, such as synaptic plasticity
GO:1903076 regulation of protein localization to plasma membrane
IBA
GO_REF:0000033
KEEP AS NON CORE
Summary: Synaptic/neuronal function
Reason: Important tissue-specific function
GO:0043005 neuron projection
IBA
GO_REF:0000033
KEEP AS NON CORE
Summary: Synaptic/neuronal function
Reason: Important tissue-specific function
GO:0005516 calmodulin binding
IBA
GO_REF:0000033
ACCEPT
Summary: Core kinase function
Reason: Essential CaMKII activity
Supporting Evidence:
UniProt:P11798
GO; GO:0005516; F:calmodulin binding; IDA:CAFA.
GO:0000082 G1/S transition of mitotic cell cycle
IEA
GO_REF:0000117
KEEP AS NON CORE
Summary: G1/S transition of mitotic cell cycle
Reason: Specialized cellular process
GO:0000166 nucleotide binding
IEA
GO_REF:0000043
MARK AS OVER ANNOTATED
Summary: Non-specific term
Reason: Term is too general and uninformative
GO:0004672 protein kinase activity
IEA
GO_REF:0000002
KEEP AS NON CORE
Summary: protein kinase activity
Reason: Specialized cellular process
GO:0004674 protein serine/threonine kinase activity
IEA
GO_REF:0000043
ACCEPT
Summary: Core kinase function
Reason: Essential CaMKII activity
GO:0004683 calcium/calmodulin-dependent protein kinase activity
IEA
GO_REF:0000120
ACCEPT
Summary: Core kinase function
Reason: Essential CaMKII activity
GO:0005516 calmodulin binding
IEA
GO_REF:0000120
ACCEPT
Summary: Core kinase function
Reason: Essential CaMKII activity
GO:0005524 ATP binding
IEA
GO_REF:0000120
ACCEPT
Summary: Core kinase function
Reason: Essential CaMKII activity
Supporting Evidence:
UniProt:P11798
GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
GO:0005737 cytoplasm
IEA
GO_REF:0000044
KEEP AS NON CORE
Summary: cytoplasm
Reason: Specialized cellular process
GO:0006816 calcium ion transport
IEA
GO_REF:0000117
KEEP AS NON CORE
Summary: calcium ion transport
Reason: Specialized cellular process
GO:0014069 postsynaptic density
IEA
GO_REF:0000044
ACCEPT
Summary: Synaptic/neuronal function
Reason: Essential for CaMKII function
GO:0016301 kinase activity
IEA
GO_REF:0000043
ACCEPT
Summary: Core kinase function
Reason: Essential CaMKII activity
GO:0016740 transferase activity
IEA
GO_REF:0000043
ACCEPT
Summary: Core kinase function
Reason: Defines essential CaMKII catalytic activity
GO:0030425 dendrite
IEA
GO_REF:0000044
ACCEPT
Summary: Core neuronal localization/function
Reason: Essential for CaMKIIΞ± neuronal role
Supporting Evidence:
UniProt:P11798
Regulates dendritic spine development (By similarity).
GO:0043197 dendritic spine
IEA
GO_REF:0000044
ACCEPT
Summary: Core neuronal localization/function
Reason: Essential for CaMKIIΞ± neuronal role
Supporting Evidence:
UniProt:P11798
GO; GO:0043197; C:dendritic spine; ISS:UniProtKB.
GO:0043226 organelle
IEA
GO_REF:0000117
MARK AS OVER ANNOTATED
Summary: Non-specific term
Reason: Term is too general and uninformative
GO:0045202 synapse
IEA
GO_REF:0000044
ACCEPT
Summary: Core neuronal localization/function
Reason: Essential for CaMKIIΞ± neuronal role
GO:0046872 metal ion binding
IEA
GO_REF:0000043
MARK AS OVER ANNOTATED
Summary: Non-specific term
Reason: Term is too general and uninformative
GO:0106310 protein serine kinase activity
IEA
GO_REF:0000116
ACCEPT
Summary: Core kinase function
Reason: Defines essential CaMKII catalytic activity
GO:0005515 protein binding
IPI
PMID:10862698
Proteomic analysis of NMDA receptor-adhesion protein signali...
MARK AS OVER ANNOTATED
Summary: Non-specific term
Reason: Term is too general and uninformative
Supporting Evidence:
PMID:10862698
Proteomic analysis of NMDA receptor-adhesion protein signaling complexes.
GO:0005515 protein binding
IPI
PMID:16120608
Multivalent interactions of calcium/calmodulin-dependent pro...
MARK AS OVER ANNOTATED
Summary: Non-specific term
Reason: Term is too general and uninformative
Supporting Evidence:
PMID:16120608
2005 Aug 24. Multivalent interactions of calcium/calmodulin-dependent protein kinase II with the postsynaptic density proteins NR2B, densin-180, and alpha-actinin-2.
GO:0005515 protein binding
IPI
PMID:16710293
NR2B tyrosine phosphorylation modulates fear learning as wel...
MARK AS OVER ANNOTATED
Summary: Non-specific term
Reason: Term is too general and uninformative
Supporting Evidence:
PMID:16710293
May 18. NR2B tyrosine phosphorylation modulates fear learning as well as amygdaloid synaptic plasticity.
GO:0005515 protein binding
IPI
PMID:19455133
Targeted tandem affinity purification of PSD-95 recovers cor...
MARK AS OVER ANNOTATED
Summary: Non-specific term
Reason: Term is too general and uninformative
Supporting Evidence:
PMID:19455133
Targeted tandem affinity purification of PSD-95 recovers core postsynaptic complexes and schizophrenia susceptibility proteins.
GO:0005515 protein binding
IPI
PMID:20141836
DAPK1 interaction with NMDA receptor NR2B subunits mediates ...
MARK AS OVER ANNOTATED
Summary: Non-specific term
Reason: Term is too general and uninformative
Supporting Evidence:
PMID:20141836
DAPK1 interaction with NMDA receptor NR2B subunits mediates brain damage in stroke.
GO:0005515 protein binding
IPI
PMID:22234183
CaMKII binding to GluN2B is critical during memory consolida...
MARK AS OVER ANNOTATED
Summary: Non-specific term
Reason: Term is too general and uninformative
Supporting Evidence:
PMID:22234183
CaMKII binding to GluN2B is critical during memory consolidation.
GO:0005515 protein binding
IPI
PMID:24725413
Activity-dependent p25 generation regulates synaptic plastic...
MARK AS OVER ANNOTATED
Summary: Non-specific term
Reason: Term is too general and uninformative
Supporting Evidence:
PMID:24725413
Activity-dependent p25 generation regulates synaptic plasticity and AΞ²-induced cognitive impairment.
GO:0005515 protein binding
IPI
PMID:28130356
A Novel Human CAMK2A Mutation Disrupts Dendritic Morphology ...
MARK AS OVER ANNOTATED
Summary: Non-specific term
Reason: Term is too general and uninformative
Supporting Evidence:
PMID:28130356
Epub 2017 Jan 27. A Novel Human CAMK2A Mutation Disrupts Dendritic Morphology and Synaptic Transmission, and Causes ASD-Related Behaviors.
GO:0005515 protein binding
IPI
PMID:28671696
Spatiotemporal profile of postsynaptic interactomes integrat...
MARK AS OVER ANNOTATED
Summary: Non-specific term
Reason: Term is too general and uninformative
Supporting Evidence:
PMID:28671696
Spatiotemporal profile of postsynaptic interactomes integrates components of complex brain disorders.
GO:0004674 protein serine/threonine kinase activity
ISO
GO_REF:0000119
ACCEPT
Summary: Core kinase function
Reason: Essential CaMKII activity
GO:0004683 calcium/calmodulin-dependent protein kinase activity
ISO
GO_REF:0000119
ACCEPT
Summary: Core kinase function
Reason: Essential CaMKII activity
GO:0005516 calmodulin binding
ISO
GO_REF:0000119
ACCEPT
Summary: Core kinase function
Reason: Essential CaMKII activity
GO:0005954 calcium- and calmodulin-dependent protein kinase complex
ISO
GO_REF:0000119
ACCEPT
Summary: Core kinase function
Reason: Defines essential CaMKII catalytic activity
GO:0006468 protein phosphorylation
ISO
GO_REF:0000119
ACCEPT
Summary: Core kinase function
Reason: Essential CaMKII activity
GO:0016301 kinase activity
ISO
GO_REF:0000119
ACCEPT
Summary: Core kinase function
Reason: Essential CaMKII activity
GO:0035458 cellular response to interferon-beta
ISO
GO_REF:0000119
KEEP AS NON CORE
Summary: Signaling pathway involvement
Reason: Downstream signaling role
GO:0038166 angiotensin-activated signaling pathway
ISO
GO_REF:0000119
KEEP AS NON CORE
Summary: Signaling pathway involvement
Reason: Downstream signaling role
GO:0042802 identical protein binding
ISO
GO_REF:0000119
MARK AS OVER ANNOTATED
Summary: Non-specific term
Reason: Term is too general and uninformative
GO:0042803 protein homodimerization activity
ISO
GO_REF:0000119
MARK AS OVER ANNOTATED
Summary: Non-specific term
Reason: Term is too general and uninformative
GO:0043197 dendritic spine
ISO
GO_REF:0000119
ACCEPT
Summary: Core neuronal localization/function
Reason: Essential for CaMKIIΞ± neuronal role
GO:0046427 positive regulation of receptor signaling pathway via JAK-STAT
ISO
GO_REF:0000119
KEEP AS NON CORE
Summary: Signaling pathway involvement
Reason: Downstream signaling role
GO:0060996 dendritic spine development
ISO
GO_REF:0000119
ACCEPT
Summary: Core neuronal localization/function
Reason: Essential for CaMKIIΞ± neuronal role
GO:0071346 cellular response to type II interferon
ISO
GO_REF:0000119
KEEP AS NON CORE
Summary: Signaling pathway involvement
Reason: Downstream signaling role
GO:0110076 negative regulation of ferroptosis
ISO
GO_REF:0000119
KEEP AS NON CORE
Summary: negative regulation of ferroptosis
Reason: Specialized cellular process
GO:1990443 peptidyl-threonine autophosphorylation
ISO
GO_REF:0000119
ACCEPT
Summary: Core kinase function
Reason: Defines essential CaMKII catalytic activity
GO:2001222 regulation of neuron migration
ISO
GO_REF:0000119
KEEP AS NON CORE
Summary: Synaptic/neuronal function
Reason: Important tissue-specific function
GO:0004674 protein serine/threonine kinase activity
IMP
PMID:23502535
CaMKII regulates diacylglycerol lipase-Ξ± and striatal endoca...
ACCEPT
Summary: Core kinase function
Reason: Essential CaMKII activity
Supporting Evidence:
PMID:23502535
CaMKII regulates diacylglycerol lipase-Ξ± and striatal endocannabinoid signaling.
GO:0004674 protein serine/threonine kinase activity
IMP
PMID:28130356
A Novel Human CAMK2A Mutation Disrupts Dendritic Morphology ...
ACCEPT
Summary: Core kinase function
Reason: Essential CaMKII activity
Supporting Evidence:
PMID:28130356
Epub 2017 Jan 27. A Novel Human CAMK2A Mutation Disrupts Dendritic Morphology and Synaptic Transmission, and Causes ASD-Related Behaviors.
GO:0006468 protein phosphorylation
ISO
GO_REF:0000096
ACCEPT
Summary: Core kinase function
Reason: Essential CaMKII activity
GO:0018105 peptidyl-serine phosphorylation
ISO
GO_REF:0000096
ACCEPT
Summary: Core kinase function
Reason: Essential CaMKII activity
GO:0046777 protein autophosphorylation
ISO
GO_REF:0000096
ACCEPT
Summary: Core kinase function
Reason: Essential CaMKII activity
GO:0004683 calcium/calmodulin-dependent protein kinase activity
ISO
GO_REF:0000096
ACCEPT
Summary: Core kinase function
Reason: Essential CaMKII activity
GO:0007259 cell surface receptor signaling pathway via JAK-STAT
ISO
GO_REF:0000119
KEEP AS NON CORE
Summary: Signaling pathway involvement
Reason: Downstream signaling role
GO:0014069 postsynaptic density
ISO
GO_REF:0000096
ACCEPT
Summary: Synaptic/neuronal function
Reason: Essential for CaMKII function
ISO
GO_REF:0000096
KEEP AS NON CORE
Summary: Synaptic/neuronal function
Reason: Important tissue-specific function
GO:0030425 dendrite
ISO
GO_REF:0000096
ACCEPT
Summary: Core neuronal localization/function
Reason: Essential for CaMKIIΞ± neuronal role
GO:0032794 GTPase activating protein binding
ISO
GO_REF:0000096
KEEP AS NON CORE
Summary: GTPase activating protein binding
Reason: Specialized cellular process
GO:0032839 dendrite cytoplasm
ISO
GO_REF:0000096
KEEP AS NON CORE
Summary: Synaptic/neuronal function
Reason: Important tissue-specific function
GO:0035235 ionotropic glutamate receptor signaling pathway
ISO
GO_REF:0000096
KEEP AS NON CORE
Summary: Synaptic/neuronal function
Reason: Important tissue-specific function
GO:0043025 neuronal cell body
ISO
GO_REF:0000096
KEEP AS NON CORE
Summary: Synaptic/neuronal function
Reason: Important tissue-specific function
GO:0098696 regulation of neurotransmitter receptor localization to postsynaptic specialization membrane
ISO
GO_REF:0000096
KEEP AS NON CORE
Summary: Synaptic/neuronal function
Reason: Important tissue-specific function
GO:0098877 neurotransmitter receptor transport to plasma membrane
ISO
GO_REF:0000096
KEEP AS NON CORE
Summary: Synaptic/neuronal function
Reason: Important tissue-specific function
GO:0098978 glutamatergic synapse
ISO
GO_REF:0000096
KEEP AS NON CORE
Summary: Synaptic/neuronal function
Reason: Important tissue-specific function
GO:0099523 presynaptic cytosol
ISO
GO_REF:0000096
ACCEPT
Summary: Synaptic/neuronal function
Reason: Essential for CaMKII function
GO:0099524 postsynaptic cytosol
ISO
GO_REF:0000096
KEEP AS NON CORE
Summary: Synaptic/neuronal function
Reason: Important tissue-specific function
GO:1903076 regulation of protein localization to plasma membrane
ISO
GO_REF:0000096
KEEP AS NON CORE
Summary: Synaptic/neuronal function
Reason: Important tissue-specific function
GO:0110076 negative regulation of ferroptosis
ISS
GO_REF:0000024
KEEP AS NON CORE
Summary: negative regulation of ferroptosis
Reason: Specialized cellular process
GO:0098685 Schaffer collateral - CA1 synapse
IMP
PMID:17660813
Kinase activity is not required for alphaCaMKII-dependent pr...
ACCEPT
Summary: Core neuronal localization/function
Reason: Essential for CaMKIIΞ± neuronal role
Supporting Evidence:
PMID:17660813
Kinase activity is not required for alphaCaMKII-dependent presynaptic plasticity at CA3-CA1 synapses.
GO:0098685 Schaffer collateral - CA1 synapse
IDA
PMID:17660813
Kinase activity is not required for alphaCaMKII-dependent pr...
ACCEPT
Summary: Core neuronal localization/function
Reason: Essential for CaMKIIΞ± neuronal role
Supporting Evidence:
PMID:17660813
Kinase activity is not required for alphaCaMKII-dependent presynaptic plasticity at CA3-CA1 synapses.
GO:0099148 regulation of synaptic vesicle docking
IMP
PMID:17660813
Kinase activity is not required for alphaCaMKII-dependent pr...
MODIFY
Summary: Presynaptic, kinase-independent regulation of docked-vesicle number and short-term plasticity at CA3-CA1 synapses; the annotated term is now obsolete.
Reason: GO:0099148 regulation of synaptic vesicle docking was obsoleted (GO release 2026-07-26) because synaptic vesicle docking is now represented as the molecular function GO:0160321 vesicle docking activity. CaMKIIalpha is not itself a docking adaptor; PMID:17660813 shows it regulates the number of docked vesicles and is required for normal short-term presynaptic plasticity through a nonenzymatic role, so the finding is best carried by the live regulatory process GO:0048172 regulation of short-term neuronal synaptic plasticity rather than transferred to the docking-activity MF.
Supporting Evidence:
PMID:17660813
alphaCaMKII regulates the number of docked vesicles independent of its ability to be activated
PMID:17660813
is required for normal short-term presynaptic plasticity
GO:0099148 regulation of synaptic vesicle docking
IDA
PMID:17660813
Kinase activity is not required for alphaCaMKII-dependent pr...
MODIFY
Summary: Presynaptic, kinase-independent regulation of docked-vesicle number and short-term plasticity at CA3-CA1 synapses; the annotated term is now obsolete.
Reason: GO:0099148 regulation of synaptic vesicle docking was obsoleted (GO release 2026-07-26) because synaptic vesicle docking is now represented as the molecular function GO:0160321 vesicle docking activity. CaMKIIalpha is not itself a docking adaptor; PMID:17660813 shows it regulates the number of docked vesicles and is required for normal short-term presynaptic plasticity through a nonenzymatic role, so the finding is best carried by the live regulatory process GO:0048172 regulation of short-term neuronal synaptic plasticity rather than transferred to the docking-activity MF.
Supporting Evidence:
PMID:17660813
alphaCaMKII regulates the number of docked vesicles independent of its ability to be activated
PMID:17660813
is required for normal short-term presynaptic plasticity
GO:0035458 cellular response to interferon-beta
ISS
GO_REF:0000024
KEEP AS NON CORE
Summary: Signaling pathway involvement
Reason: Downstream signaling role
GO:0046427 positive regulation of receptor signaling pathway via JAK-STAT
ISS
GO_REF:0000024
KEEP AS NON CORE
Summary: Signaling pathway involvement
Reason: Downstream signaling role
GO:0045202 synapse
IDA
PMID:28642476
Prevention of long-term memory loss after retrieval by an en...
ACCEPT
Summary: Core neuronal localization/function
Reason: Essential for CaMKIIΞ± neuronal role
Supporting Evidence:
PMID:28642476
Prevention of long-term memory loss after retrieval by an endogenous CaMKII inhibitor.
GO:0048168 regulation of neuronal synaptic plasticity
IMP
PMID:17610578
Alpha-synuclein involvement in hippocampal synaptic plastici...
ACCEPT
Summary: Synaptic/neuronal function
Reason: Essential for CaMKII function
Supporting Evidence:
PMID:17610578
Alpha-synuclein involvement in hippocampal synaptic plasticity: role of NO, cGMP, cGK and CaMKII.
GO:1902108 regulation of mitochondrial membrane permeability involved in apoptotic process
IMP
PMID:23051746
CaMKII determines mitochondrial stress responses in heart.
KEEP AS NON CORE
Summary: regulation of mitochondrial membrane per...
Reason: Specialized cellular process
Supporting Evidence:
PMID:23051746
CaMKII determines mitochondrial stress responses in heart.
GO:0005515 protein binding
IPI
PMID:23502535
CaMKII regulates diacylglycerol lipase-Ξ± and striatal endoca...
MARK AS OVER ANNOTATED
Summary: Non-specific term
Reason: Term is too general and uninformative
Supporting Evidence:
PMID:23502535
CaMKII regulates diacylglycerol lipase-Ξ± and striatal endocannabinoid signaling.
GO:2000124 regulation of endocannabinoid signaling pathway
IMP
PMID:23502535
CaMKII regulates diacylglycerol lipase-Ξ± and striatal endoca...
KEEP AS NON CORE
Summary: Signaling pathway involvement
Reason: Downstream signaling role
Supporting Evidence:
PMID:23502535
CaMKII regulates diacylglycerol lipase-Ξ± and striatal endocannabinoid signaling.
GO:0005954 calcium- and calmodulin-dependent protein kinase complex
ISS
GO_REF:0000024
ACCEPT
Summary: Core kinase function
Reason: Defines essential CaMKII catalytic activity
GO:0043197 dendritic spine
ISS
GO_REF:0000024
ACCEPT
Summary: Core neuronal localization/function
Reason: Essential for CaMKIIΞ± neuronal role
GO:0060996 dendritic spine development
ISS
GO_REF:0000024
ACCEPT
Summary: Core neuronal localization/function
Reason: Essential for CaMKIIΞ± neuronal role
GO:2001222 regulation of neuron migration
ISS
GO_REF:0000024
KEEP AS NON CORE
Summary: Synaptic/neuronal function
Reason: Important tissue-specific function
GO:0005739 mitochondrion
IDA
PMID:23051746
CaMKII determines mitochondrial stress responses in heart.
KEEP AS NON CORE
Summary: mitochondrion
Reason: Specialized cellular process
Supporting Evidence:
PMID:23051746
CaMKII determines mitochondrial stress responses in heart.
GO:0004683 calcium/calmodulin-dependent protein kinase activity
IDA
PMID:15994560
Variable control of Ets-1 DNA binding by multiple phosphates...
ACCEPT
Summary: Core kinase function
Reason: Essential CaMKII activity
Supporting Evidence:
PMID:15994560
Variable control of Ets-1 DNA binding by multiple phosphates in an unstructured region.
GO:0005516 calmodulin binding
IDA
PMID:15994560
Variable control of Ets-1 DNA binding by multiple phosphates...
ACCEPT
Summary: Core kinase function
Reason: Essential CaMKII activity
Supporting Evidence:
PMID:15994560
Variable control of Ets-1 DNA binding by multiple phosphates in an unstructured region.
GO:0005515 protein binding
IPI
PMID:25297099
The schizophrenia susceptibility gene dysbindin regulates de...
MARK AS OVER ANNOTATED
Summary: Non-specific term
Reason: Term is too general and uninformative
Supporting Evidence:
PMID:25297099
The schizophrenia susceptibility gene dysbindin regulates dendritic spine dynamics.
GO:0048813 dendrite morphogenesis
IMP
PMID:25297099
The schizophrenia susceptibility gene dysbindin regulates de...
ACCEPT
Summary: Core neuronal localization/function
Reason: Essential for CaMKIIΞ± neuronal role
Supporting Evidence:
PMID:25297099
The schizophrenia susceptibility gene dysbindin regulates dendritic spine dynamics.
GO:0014069 postsynaptic density
IDA
PMID:17114649
Qualitative and quantitative analyses of protein phosphoryla...
ACCEPT
Summary: Synaptic/neuronal function
Reason: Essential for CaMKII function
Supporting Evidence:
PMID:17114649
Epub 2006 Nov 17. Qualitative and quantitative analyses of protein phosphorylation in naive and stimulated mouse synaptosomal preparations.
GO:0002931 response to ischemia
IMP
PMID:23051746
CaMKII determines mitochondrial stress responses in heart.
UNDECIDED
Summary: The cited heart study supports CaMKII inhibitor/activity effects but does not clearly distinguish Camk2a/CaMKIIalpha-specific biology.
Reason: Evidence is not clearly Camk2a-specific
Supporting Evidence:
PMID:23051746
CaMKII determines mitochondrial stress responses in heart.
GO:0004674 protein serine/threonine kinase activity
IMP
PMID:23051746
CaMKII determines mitochondrial stress responses in heart.
UNDECIDED
Summary: The cited heart study supports CaMKII activity broadly but does not clearly establish Camk2a/CaMKIIalpha-specific kinase activity.
Reason: Evidence is not clearly Camk2a-specific
Supporting Evidence:
PMID:23051746
CaMKII determines mitochondrial stress responses in heart.
GO:0010666 positive regulation of cardiac muscle cell apoptotic process
IMP
PMID:23051746
CaMKII determines mitochondrial stress responses in heart.
UNDECIDED
Summary: Cardiac apoptosis effects are from a broad CaMKII heart context and are not clearly Camk2a/CaMKIIalpha-specific.
Reason: Evidence is not clearly Camk2a-specific
Supporting Evidence:
PMID:23051746
CaMKII determines mitochondrial stress responses in heart.
GO:0018105 peptidyl-serine phosphorylation
IMP
PMID:23051746
CaMKII determines mitochondrial stress responses in heart.
UNDECIDED
Summary: The cited heart study supports CaMKII activity broadly but does not clearly establish Camk2a/CaMKIIalpha-specific serine phosphorylation.
Reason: Evidence is not clearly Camk2a-specific
Supporting Evidence:
PMID:23051746
CaMKII determines mitochondrial stress responses in heart.
GO:0051928 positive regulation of calcium ion transport
IMP
PMID:23051746
CaMKII determines mitochondrial stress responses in heart.
UNDECIDED
Summary: Calcium transport effects are from a broad CaMKII heart context and are not clearly Camk2a/CaMKIIalpha-specific.
Reason: Evidence is not clearly Camk2a-specific
Supporting Evidence:
PMID:23051746
CaMKII determines mitochondrial stress responses in heart.
GO:0004674 protein serine/threonine kinase activity
IDA
PMID:18480293
Phosphorylation of Homer3 by calcium/calmodulin-dependent ki...
ACCEPT
Summary: Core kinase function
Reason: Essential CaMKII activity
Supporting Evidence:
PMID:18480293
Phosphorylation of Homer3 by calcium/calmodulin-dependent kinase II regulates a coupling state of its target molecules in Purkinje cells.
GO:0005515 protein binding
IPI
PMID:15140879
Regulation of the multifunctional Ca2+/calmodulin-dependent ...
MARK AS OVER ANNOTATED
Summary: Non-specific term
Reason: Term is too general and uninformative
Supporting Evidence:
PMID:15140879
2004 Mar 31. Regulation of the multifunctional Ca2+/calmodulin-dependent protein kinase II by the PP2C phosphatase PPM1F in fibroblasts.
GO:0035254 glutamate receptor binding
IPI
PMID:16710293
NR2B tyrosine phosphorylation modulates fear learning as wel...
ACCEPT
Summary: GluN2B/NMDA receptor binding is a central non-catalytic synaptic scaffolding interaction for CaMKIIalpha.
Reason: Core non-catalytic CaMKIIalpha synaptic function
Supporting Evidence:
PMID:16710293
May 18. NR2B tyrosine phosphorylation modulates fear learning as well as amygdaloid synaptic plasticity.
PMID:22234183
CaMKII binding to GluN2B is critical during memory consolidation.
file:mouse/Camk2a/Camk2a-deep-research-falcon.md
Falcon synthesis identifies GluN2B/NMDAR binding as a central CaMKIIalpha structural and scaffolding function.
GO:0005515 protein binding
IPI
PMID:12223541
The cyclin-dependent kinase 5 activators p35 and p39 interac...
MARK AS OVER ANNOTATED
Summary: Non-specific term
Reason: Term is too general and uninformative
Supporting Evidence:
PMID:12223541
The cyclin-dependent kinase 5 activators p35 and p39 interact with the alpha-subunit of Ca2+/calmodulin-dependent protein kinase II and alpha-actinin-1 in a calcium-dependent manner.
GO:0000082 G1/S transition of mitotic cell cycle
IMP
PMID:12660151
Calcineurin-independent regulation of plasma membrane Ca2+ A...
UNDECIDED
Summary: The cited vascular smooth muscle study supports CaMKII activity broadly but does not clearly establish Camk2a/CaMKIIalpha-specific cell-cycle biology.
Reason: Evidence is not clearly Camk2a-specific
Supporting Evidence:
PMID:12660151
Calcineurin-independent regulation of plasma membrane Ca2+ ATPase-4 in the vascular smooth muscle cell cycle.
GO:0004674 protein serine/threonine kinase activity
IMP
PMID:12660151
Calcineurin-independent regulation of plasma membrane Ca2+ A...
UNDECIDED
Summary: The cited vascular smooth muscle study supports CaMKII activity broadly but does not clearly establish Camk2a/CaMKIIalpha-specific kinase activity.
Reason: Evidence is not clearly Camk2a-specific
Supporting Evidence:
PMID:12660151
Calcineurin-independent regulation of plasma membrane Ca2+ ATPase-4 in the vascular smooth muscle cell cycle.
GO:0006816 calcium ion transport
IMP
PMID:12660151
Calcineurin-independent regulation of plasma membrane Ca2+ A...
UNDECIDED
Summary: The cited vascular smooth muscle study is not clear evidence for a Camk2a-specific calcium transport annotation.
Reason: Evidence is not clearly Camk2a-specific
Supporting Evidence:
PMID:12660151
Calcineurin-independent regulation of plasma membrane Ca2+ ATPase-4 in the vascular smooth muscle cell cycle.
GO:0046777 protein autophosphorylation
IMP
PMID:12660151
Calcineurin-independent regulation of plasma membrane Ca2+ A...
UNDECIDED
Summary: The cited vascular smooth muscle study supports CaMKII activity broadly but does not clearly establish Camk2a/CaMKIIalpha-specific autophosphorylation.
Reason: Evidence is not clearly Camk2a-specific
Supporting Evidence:
PMID:12660151
Calcineurin-independent regulation of plasma membrane Ca2+ ATPase-4 in the vascular smooth muscle cell cycle.
GO:0046928 regulation of neurotransmitter secretion
IMP
PMID:12629219
Essential function of alpha-calcium/calmodulin-dependent pro...
ACCEPT
Summary: Synaptic/neuronal function
Reason: Essential for CaMKII function
Supporting Evidence:
PMID:12629219
Essential function of alpha-calcium/calmodulin-dependent protein kinase II in neurotransmitter release at a glutamatergic central synapse.

Core Functions

Phosphorylates serine/threonine residues on target proteins in response to Ca2+/calmodulin activation. Autophosphorylation at Thr-286 switches kinase to constitutively active state.

Supporting Evidence:
  • UniProt:P11798
    Calcium/calmodulin-dependent protein kinase that functions autonomously after Ca2+/calmodulin binding and autophosphorylation.
  • file:mouse/Camk2a/Camk2a-deep-research-falcon.md
    Falcon synthesis supports CaMKIIalpha as a Ca2+/calmodulin-regulated Ser/Thr kinase with T286 autophosphorylation and postsynaptic substrate phosphorylation as central activities.

Binds the NMDA receptor GluN2B subunit at stimulated synapses, providing a non-catalytic scaffold that localizes autonomous CaMKIIalpha activity during early long-term potentiation and memory consolidation.

Supporting Evidence:
  • PMID:22234183
    CaMKII binding to GluN2B is critical during memory consolidation.
  • file:mouse/Camk2a/Camk2a-deep-research-falcon.md
    Falcon synthesis identifies GluN2B/NMDAR binding as a core CaMKIIalpha structural and scaffolding function at excitatory synapses.

Binds Ca2+/calmodulin through the regulatory segment, relieving autoinhibition and enabling kinase activation and T286 trans-autophosphorylation.

Molecular Function:
calmodulin binding
Directly Involved In:
Cellular Locations:
Supporting Evidence:
  • UniProt:P11798
    Calcium/calmodulin-dependent protein kinase that functions autonomously after Ca2+/calmodulin binding and autophosphorylation.
  • file:mouse/Camk2a/Camk2a-deep-research-falcon.md
    Falcon synthesis describes Ca2+/calmodulin binding to the regulatory segment as the activation mechanism for CaMKIIalpha holoenzymes.

References

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Suggested Questions for Experts

Q: GO obsoleted GO:0099148 regulation of synaptic vesicle docking together with GO:0106020/GO:0106021/GO:0106022 (regulation of vesicle docking), leaving no live term for a protein that changes the number of docked vesicles without itself having GO:0160321 vesicle docking activity. PMID:17660813 reports that alphaCaMKII regulates the number of docked vesicles through a nonenzymatic role. Should this be represented as a regulator of GO:0160321 activity (for example a GO-CAM causal link to the docking-activity annoton of a partner protein, or a new MF regulator term), rather than only through GO:0048172 regulation of short-term neuronal synaptic plasticity?

Suggested experts: SynGO curators, Presynaptic physiologists

Deep Research

Falcon

(Camk2a-deep-research-falcon.md)

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πŸ“„ View Raw YAML

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