Camk2a

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 CaMKIIα 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 CaMKIIα 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 CaMKIIα 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 Aβ-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 CaMKIIα 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 CaMKIIα 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-α and striatal endoca...	ACCEPT	Summary: Core kinase function Reason: Essential CaMKII activity Supporting Evidence: PMID:23502535 CaMKII regulates diacylglycerol lipase-α 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
GO:0030424 axon	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 CaMKIIα 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 CaMKIIα 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 CaMKIIα 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...	ACCEPT	Summary: Synaptic/neuronal function Reason: Essential for CaMKII function 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	IDA PMID:17660813 Kinase activity is not required for alphaCaMKII-dependent pr...	ACCEPT	Summary: Synaptic/neuronal function Reason: Essential for CaMKII function Supporting Evidence: PMID:17660813 Kinase activity is not required for alphaCaMKII-dependent presynaptic plasticity at CA3-CA1 synapses.
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 CaMKIIα 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-α 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-α and striatal endocannabinoid signaling.
GO:2000124 regulation of endocannabinoid signaling pathway	IMP PMID:23502535 CaMKII regulates diacylglycerol lipase-α and striatal endoca...	KEEP AS NON CORE	Summary: Signaling pathway involvement Reason: Downstream signaling role Supporting Evidence: PMID:23502535 CaMKII regulates diacylglycerol lipase-α 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 CaMKIIα neuronal role
GO:0060996 dendritic spine development	ISS GO_REF:0000024	ACCEPT	Summary: Core neuronal localization/function Reason: Essential for CaMKIIα 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 CaMKIIα 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.

Molecular Function:

calcium/calmodulin-dependent protein kinase activity

Directly Involved In:

protein phosphorylation peptidyl-serine phosphorylation protein autophosphorylation

Cellular Locations:

synapse postsynaptic density dendritic spine

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.

Molecular Function:

glutamate receptor binding

Directly Involved In:

regulation of neuronal synaptic plasticity

Cellular Locations:

Schaffer collateral - CA1 synapse postsynaptic density

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:

protein phosphorylation

Cellular Locations:

dendritic spine dendrite

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

GO_REF:0000002

Gene Ontology annotation through association of InterPro records with GO terms

GO_REF:0000024

Manual transfer of experimentally-verified manual GO annotation data to orthologs by curator judgment of sequence similarity

GO_REF:0000033

Annotation inferences using phylogenetic trees

GO_REF:0000043

Gene Ontology annotation based on UniProtKB/Swiss-Prot keyword mapping

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:0000096

Automated transfer of experimentally-verified manual GO annotation data to mouse-rat orthologs

UniProt:P11798

UniProt record for Camk2a (P11798)

GO_REF:0000116

Automatic Gene Ontology annotation based on Rhea mapping

GO_REF:0000117

Electronic Gene Ontology annotations created by ARBA machine learning models

GO_REF:0000119

Automated transfer of experimentally-verified manual GO annotation data to mouse-human orthologs

GO_REF:0000120

Combined Automated Annotation using Multiple IEA Methods

PMID:10862698

Proteomic analysis of NMDA receptor-adhesion protein signaling complexes.

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.

PMID:12629219

Essential function of alpha-calcium/calmodulin-dependent protein kinase II in neurotransmitter release at a glutamatergic central synapse.

PMID:12660151

Calcineurin-independent regulation of plasma membrane Ca2+ ATPase-4 in the vascular smooth muscle cell cycle.

PMID:15140879

Regulation of the multifunctional Ca2+/calmodulin-dependent protein kinase II by the PP2C phosphatase PPM1F in fibroblasts.

PMID:15994560

Variable control of Ets-1 DNA binding by multiple phosphates in an unstructured region.

PMID:16120608

Multivalent interactions of calcium/calmodulin-dependent protein kinase II with the postsynaptic density proteins NR2B, densin-180, and alpha-actinin-2.

PMID:16710293

NR2B tyrosine phosphorylation modulates fear learning as well as amygdaloid synaptic plasticity.

PMID:17114649

Qualitative and quantitative analyses of protein phosphorylation in naive and stimulated mouse synaptosomal preparations.

PMID:17610578

Alpha-synuclein involvement in hippocampal synaptic plasticity: role of NO, cGMP, cGK and CaMKII.

PMID:17660813

Kinase activity is not required for alphaCaMKII-dependent presynaptic plasticity at CA3-CA1 synapses.

PMID:18480293

Phosphorylation of Homer3 by calcium/calmodulin-dependent kinase II regulates a coupling state of its target molecules in Purkinje cells.

PMID:19455133

Targeted tandem affinity purification of PSD-95 recovers core postsynaptic complexes and schizophrenia susceptibility proteins.

PMID:20141836

DAPK1 interaction with NMDA receptor NR2B subunits mediates brain damage in stroke.

PMID:22234183

CaMKII binding to GluN2B is critical during memory consolidation.

PMID:23051746

CaMKII determines mitochondrial stress responses in heart.

PMID:23502535

CaMKII regulates diacylglycerol lipase-α and striatal endocannabinoid signaling.

PMID:24725413

Activity-dependent p25 generation regulates synaptic plasticity and Aβ-induced cognitive impairment.

PMID:25297099

The schizophrenia susceptibility gene dysbindin regulates dendritic spine dynamics.

PMID:28130356

A Novel Human CAMK2A Mutation Disrupts Dendritic Morphology and Synaptic Transmission, and Causes ASD-Related Behaviors.

PMID:28642476

Prevention of long-term memory loss after retrieval by an endogenous CaMKII inhibitor.

PMID:28671696

Spatiotemporal profile of postsynaptic interactomes integrates components of complex brain disorders.

file:mouse/Camk2a/Camk2a-deep-research-falcon.md

Falcon deep research summary for mouse Camk2a

CaMKIIalpha is a Ca2+/calmodulin-regulated serine/threonine kinase whose T286 autophosphorylation and substrate phosphorylation support synaptic plasticity.
Falcon synthesis emphasizes GluN2B/NMDA receptor binding as a central non-catalytic scaffolding function at the postsynaptic density.

Deep Research

Falcon

(Camk2a-deep-research-falcon.md)

this with annotations you find in gene/protein databases, but these can be outdated or inaccurate. Falcon Edison Scientific Literature 46 citations 2026-05-03T23:47:34.397184

The research report should be a detailed narrative explaining the function, biological processes, and localization of the gene product. Citations should be given for all claims.

You should prioritize authoritative reviews and primary scientific literature when conducting research. You can supplement
this with annotations you find in gene/protein databases, but these can be outdated or inaccurate.

We are specifically interested in the primary function of the gene - for enzymes, what reaction is catalyzed, and what is the substrate specificity? For transporters, what is the substrate? For structural proteins or adapters, what is the broader structural role? For signaling molecules, what is the role in the pathway.

We are interested in where in or outside the cell the gene product carries out its function.

We are also interested in the signaling or biochemical pathways in which the gene functions. We are less interested in broad pleiotropic effects, except where these elucidate the precise role.

Include evidence where possible. We are interested in both experimental evidence as well as inference from structure, evolution, or bioinformatic analysis. Precise studies should be prioritized over high-throughput, where available.

Research report: Mouse Camk2a (CaMKIIα; UniProt P11798)—functional annotation

0) Target verification (mandatory)

The target gene/protein is mouse Camk2a, encoding calcium/calmodulin-dependent protein kinase II subunit alpha (CaMKIIα); a recent in vivo phosphoproteomics study explicitly maps CAMK2A to UniProt accession P11798 in Mus musculus. (rigter2024simultaneouslossof pages 5-8)

1) Key concepts and definitions (current understanding)

1.1 What CaMKIIα is

CaMKIIα is a Ca(^2+)/calmodulin (CaM)-regulated serine/threonine kinase that functions as both (i) an enzyme that phosphorylates Ser/Thr residues on many neuronal proteins and (ii) a structural/scaffolding hub organizing postsynaptic signaling. (brown2024studyingcamkiitools pages 1-3)

1.2 Domain architecture and holoenzyme organization

Each CaMKIIα subunit contains an N-terminal kinase domain, a regulatory domain (containing the Ca(^2+)/CaM-binding/autoinhibitory segment), a variable linker, and a C-terminal hub/association domain that assembles CaMKII into predominantly 12-mer holoenzymes. (brown2024studyingcamkiitools pages 1-3, brown2024studyingcamkiitools media 3753eb15)

1.3 Enzymatic reaction (primary biochemical function)

CaMKIIα catalyzes ATP-dependent phosphate transfer:

Reaction (general): ATP + protein-Ser/Thr → ADP + protein-Ser(P)/Thr(P)

Mechanistically, binding of Ca(^2+)/CaM relieves autoinhibition and enables substrate access to the active site. (brown2024studyingcamkiitools pages 1-3)

2) Biochemical mechanism, regulation, and substrate specificity

2.1 Ca(^2+)/CaM activation and autonomous activity

Ca(^2+)/CaM binding to the regulatory segment stimulates CaMKII activity by ~1,000-fold, largely by opening access to substrate-binding regions, and exposes the T286 site for inter-subunit trans-autophosphorylation. (brown2024studyingcamkiitools pages 1-3)

After T286 autophosphorylation, CaMKII enters a Ca(^2+)-independent “autonomous” state with approximately ~20–40% of maximal activity. (brown2024studyingcamkiitools pages 1-3)

2.2 Post-translational modifications (PTMs) emphasized in 2023–2024

(a) T286 autophosphorylation
T286 phosphorylation is a canonical route to autonomy and is tightly connected to synaptic plasticity mechanisms. (brown2024studyingcamkiitools pages 1-3, rumian2024ltpexpressionmediated pages 3-5)

(b) Regulatory-domain S-nitrosylation/oxidation (2023 advance)
Rumian et al. generated a nitrosylation/oxidation-incompetent knock-in (CaMKIIΔSNO; C280V/M281V/C289V). This mutation did not alter Ca(^2+)/CaM-stimulated activity or T286-dependent autonomous activity, but produced aging-like deficits in synaptic plasticity and memory. (rumian2023decreasednitrosylationof pages 1-3)

Mechanistically, S-nitrosylation drives basal synaptic accumulation of CaMKII through GluN2B-dependent anchoring: an NO donor (300 μM DEA-NONOate) increased synaptic CaMKII in WT neurons (n=13 control, n=20 NO; ****p<0.0001) but not in ΔSNO neurons (n=22 control, n=19 NO; n.s.) or neurons lacking the CaMKII-binding segment of GluN2B (n=11 control, n=12 NO; n.s.). (rumian2023decreasednitrosylationof pages 20-25)

A key point is specificity: LTP-like stimulation–induced CaMKII translocation (cLTP) occurred similarly in WT and ΔSNO neurons, indicating that nitrosylation is not required for acute LTP-driven movement, but is important for basal synaptic residency and specific plasticity regimes. (rumian2023decreasednitrosylationof pages 20-25)

3) Subcellular localization and pathway roles (synaptic signaling and plasticity)

3.1 Localization: postsynaptic density (PSD) and NMDAR anchoring

CaMKIIα is strongly enriched at excitatory synapses/PSD and is functionally targeted via direct binding to the NMDA receptor subunit GluN2B, aligning CaMKII signaling with Ca(^2+) influx microdomains. (rumian2024ltpexpressionmediated pages 20-24, rumian2024ltpexpressionmediated pages 6-8)

3.2 LTP pathway logic and timing (2024 advance)

Rumian et al. (2024) dissected phase-specific CaMKII requirements in hippocampal LTP:

Induction (≈ first ~5 min): requires structural binding of CaMKII to GluN2B, but not ongoing enzymatic activity during that earliest interval. (rumian2024ltpexpressionmediated pages 6-8)
Expression (≈ within ~15 min): requires enzymatic activity, specifically the autonomous activity of GluN2B-bound CaMKII generated during induction. (rumian2024ltpexpressionmediated pages 20-24)
Maintenance (>~15 min): no longer requires enzymatic CaMKII activity, while structural CaMKII–GluN2B interactions can persist. (rumian2024ltpexpressionmediated pages 20-24)

The 2024 report further connects this to established downstream plasticity effectors: in this framework, the GluN2B-anchored autonomous activity promotes processes such as SynGAP phosphorylation/removal from synapses and TARP phosphorylation that enhances AMPAR accumulation/trapping at potentiated synapses. (rumian2024ltpexpressionmediated pages 20-24)

4) Recent developments and latest research (prioritizing 2023–2024)

4.1 2024: Endogenous in vivo substrate discovery in adult mouse cortex (phosphoproteomics)

Rigter et al. (bioRxiv, Nov 2024) performed TMT phosphoproteomics after inducible adult deletion of Camk2a/Camk2b (CAG-CreESR) and identified a large set of candidate endogenous substrates under basal conditions:

Tamoxifen regimen: 0.1 mg/g i.p. × 4 consecutive days; cortex harvested 21 days after first injection. (rigter2024simultaneouslossof pages 5-8, rigter2024simultaneouslossof pages 3-5)
Depth: 5,830 phosphopeptides corresponding to 2,210 proteins. (rigter2024simultaneouslossof pages 5-8)
Differential phosphosites: 208 phosphopeptides (from 130 proteins) downregulated >1.5-fold; none upregulated. (rigter2024simultaneouslossof pages 5-8)
Protein depletion: CaMK2A and CaMK2B reduced to <10% (western blot); proteomics estimates ~12% (CaMK2A) and ~19% (CaMK2B) remaining. (rigter2024simultaneouslossof pages 5-8, rigter2024simultaneouslossof pages 15-17)

Functional enrichment implicated postsynaptic specialization / glutamatergic synapse / postsynaptic organization, consistent with a primary postsynaptic role. (rigter2024simultaneouslossof pages 10-12)

Examples of candidate endogenous substrates/pathway nodes included SHANK3 (strongest downregulated phosphopeptide; Ser1510 directly phosphorylatable by CaMK2A in vitro), DLGAP family, SYNGAP1, GRIN2A/GRIN2B, channel proteins KCNQ5 and CACNA1B, and synaptic regulators including IQSEC2. (rigter2024simultaneouslossof pages 12-15, rigter2024simultaneouslossof pages 8-10, rigter2024simultaneouslossof pages 10-12)

4.2 2023: S-nitrosylation deficit as a mechanistic explanation for age-like cognitive decline

Rumian et al. (Science Signaling, Jul 2023) linked aging-associated decline in CaMKII nitrosylation to reduced basal synaptic CaMKII and impairments in memory and theta-burst LTP, offering a mechanistic axis that is distinct from classic T286 autonomy alone. (rumian2023decreasednitrosylationof pages 6-7, rumian2023decreasednitrosylationof pages 16-20)

5) Current applications and real-world implementations

5.1 Experimental tools for CaMKIIα research (expert standards, 2024)

Brown & Bayer (Cell Reports, Apr 2024) provide an expert framework for CaMKII experimentation, emphasizing that different inhibitor classes interrogate different mechanistic states:

CaM-competitive inhibitors (KN62/KN93): block Ca(^2+)/CaM-stimulated activation but do not inhibit already autonomous CaMKII; they also have substantial off-targets (e.g., effects on Ca(^2+) and K(^+) channels). (brown2024studyingcamkiitools pages 4-6)
T-site peptide inhibitors (e.g., tatCN21/tatCN19o): can inhibit both stimulated and autonomous states and can disrupt CaMKII interactions at higher concentrations. (brown2024studyingcamkiitools pages 8-9, brown2024studyingcamkiitools pages 6-8)
ATP-competitive inhibitors (e.g., AS283/AS397; ruxolitinib): inhibit catalytic activity, but may not block—and can enhance—GluN2B-like binding. (brown2024studyingcamkiitools pages 4-6)

They recommend multiple inhibitors with distinct mechanisms as controls and note concentration translation issues due to cellular ATP (~4 mM) and CaM levels. (brown2024studyingcamkiitools pages 8-9, brown2024studyingcamkiitools pages 6-8)

A representative image-based schematic and inhibitor summary table are available in this Cell Reports paper (Figure 1 / Table 1). (brown2024studyingcamkiitools media 3753eb15)

5.2 Optogenetic control at single synapses (“local optogenetics,” 2023)

Nagasawa et al. (Jun 2023) describe photoactivatable CaMKII (paCaMKII) created by fusing/inserting the LOV2 domain into CaMKIIα, enabling two-photon activation in single dendritic spines to induce synaptic and structural LTP.

Implementation details include:
- Two-photon activation volume ~1.5 μm (spine-scale). (nagasawa2023lov2basedphotoactivatablecamkii pages 1-2)
- Example stimulation: 820 nm, 30 trains at 0.5 Hz, 80 ms/pulse, 4 mW, targeted to one spine, producing spine enlargement that relaxed to ~150% at 20–30 min and could persist >4 h (structural LTP). (nagasawa2023lov2basedphotoactivatablecamkii pages 6-8)

Brown & Bayer (2024) contextualize paCaMKII and related optogenetic inhibitors (e.g., paAIP2) as part of a standards-driven toolkit and note that paCaMKII can also respond to Ca(^2+)/CaM, requiring careful experimental interpretation. (brown2024studyingcamkiitools pages 24-26)

5.3 Camk2a regulatory elements for neuron-type targeting (Cre and AAV)

While distinct from the molecular function of CaMKIIα protein, Camk2a regulatory elements are widely used to target forebrain excitatory neurons:

In a 2024 Science Advances study, Camk2a-Cre was explicitly described as having Cre expression that starts at 2–3 weeks after birth and is restricted to forebrain excitatory neurons in hippocampus and cortex, enabling postnatal conditional genetics. (liu2024kat6adeficiencyimpairs pages 2-3)
In 2024 Communications Biology, Camk2a-Cre and Camk2a-promoter AAVs were used to target dorsal CA1 pyramidal neurons for receptor overexpression and chemogenetic manipulation (e.g., Camk2a-driven co-expression of hM3D(Gq) and GHS-R1a). (zhang2024increasedghsr1aexpression pages 2-4)

6) Relevant statistics and data highlights (recent studies)

Activation magnitude: Ca(^2+)/CaM increases CaMKII activity by ~1,000-fold; T286 autonomy yields ~20–40% of maximal activity. (brown2024studyingcamkiitools pages 1-3)
NO-driven synaptic localization: 300 μM DEA-NONOate significantly increased synaptic CaMKII in WT (n=13 control, 20 NO; ****p<0.0001) but not in ΔSNO. (rumian2023decreasednitrosylationof pages 20-25)
Behavior in ΔSNO mice (young adults): RAWM long-term memory impairment (n=21 WT, 22 ΔSNO; p=0.012); contextual fear conditioning reduced freezing (p=0.007 young; p=0.0226 middle-aged). (rumian2023decreasednitrosylationof pages 16-20)
Electrophysiology: ΔSNO mice show reduced TBS-LTP (n=8 WT vs 9 ΔSNO; p=0.022) but normal HFS-LTP. (rumian2023decreasednitrosylationof pages 16-20)
In vivo substrate discovery scale: adult cortex phosphoproteomics identified 5,830 phosphopeptides (2,210 proteins) and 208 downregulated phosphopeptides from 130 proteins after Camk2a/b deletion; no upregulated sites. (rigter2024simultaneouslossof pages 5-8)

7) Expert synthesis and interpretation

Recent 2023–2024 work reinforces a view of CaMKIIα as a state-dependent integrator that couples transient Ca(^2+) transients to persistent synaptic change through (i) catalytic phosphorylation, (ii) regulated autonomous activity, and (iii) stable localization to synapses via GluN2B binding. The 2024 LTP-phase dissection indicates that CaMKII catalytic activity is not uniformly required over time; instead, requirement is confined to a specific early post-induction window, while longer maintenance relies more on structural persistence and downstream consolidation mechanisms. (rumian2024ltpexpressionmediated pages 20-24, rumian2024ltpexpressionmediated pages 6-8)

Concurrently, Rumian et al. (2023) highlight that basal synaptic residency is itself a regulated property (e.g., via S-nitrosylation), and that loss of this regulation can yield aging-like cognitive phenotypes even without altering core Ca(^2+)/CaM activation or T286 autonomy. (rumian2023decreasednitrosylationof pages 1-3, rumian2023decreasednitrosylationof pages 16-20)

8) Summary table of findings

The following table compiles key concepts, 2023–2024 developments, quantitative data, and applications into a single evidence map.

Topic (definition/concept)	Key points	2023-2024 evidence highlights	Quantitative/statistics	Primary source(s) with DOI/URL and publication month/year
Enzyme reaction & substrates	Mouse Camk2a encodes CaMKIIα, a Ca(^{2+})/calmodulin-regulated Ser/Thr protein kinase. It phosphorylates Ser/Thr residues on synaptic substrates and also has non-enzymatic structural/scaffolding functions. Recent in vivo substrate work places major targets in postsynaptic organization and glutamatergic signaling, including SHANK3, DLGAP family proteins, SYNGAP1, GRIN2A/GRIN2B, KCNQ5, CACNA1B, IQSEC2, and others. Consensus features include a basic residue at -3, hydrophobic residues at -5/+1, and often an acidic residue at +2, but validated substrates do not always perfectly match the motif. (brown2024studyingcamkiitools pages 1-3, rigter2024simultaneouslossof pages 12-15, rigter2024simultaneouslossof pages 8-10, rigter2024simultaneouslossof pages 10-12)	Adult mouse cortex double Camk2a/Camk2b loss revealed many endogenous candidate substrates not previously assigned to CAMK2, including a strong effect at SHANK3 Ser1510; the study also refined the in vivo motif and showed substrate-dependent contribution of the +2 acidic residue. (rigter2024simultaneouslossof pages 12-15, rigter2024simultaneouslossof pages 10-12)	5,830 phosphopeptides from 2,210 proteins identified; 208 phosphopeptides from 130 proteins downregulated >1.5-fold; ~75% of sites matched at least 3 of 5 consensus positions; 113 novel potential substrates reported. (rigter2024simultaneouslossof pages 5-8, rigter2024simultaneouslossof pages 10-12)	Brown & Bayer, Cell Reports (Apr 2024), doi:10.1016/j.celrep.2024.113982, https://doi.org/10.1016/j.celrep.2024.113982; Rigter et al., bioRxiv (Nov 2024), doi:10.1101/2024.11.17.624016, https://doi.org/10.1101/2024.11.17.624016
Activation mechanism	CaMKIIα subunits contain kinase, regulatory, linker, and hub domains and assemble mainly as 12-mer holoenzymes. Ca(^{2+})/CaM binds the regulatory segment, relieves autoinhibition, exposes the substrate-binding S-site and T-site, and enables neighboring subunits to trans-autophosphorylate T286. (brown2024studyingcamkiitools pages 1-3, brown2024studyingcamkiitools media 3753eb15)	Expert guidance in 2024 emphasizes that activation should be interpreted at the holoenzyme level, with Ca(^{2+})/CaM binding and T286 trans-autophosphorylation as central mechanistic events. Domain architecture and conformational logic are summarized in figure/table resources. (brown2024studyingcamkiitools pages 1-3, brown2024studyingcamkiitools media 3753eb15)	Ca(^{2+})/CaM causes an approximately ~1,000-fold increase in enzymatic activity; T286 autophosphorylation requires two Ca(^{2+})/CaM molecules on neighboring subunits. (brown2024studyingcamkiitools pages 1-3)	Brown & Bayer, Cell Reports (Apr 2024), doi:10.1016/j.celrep.2024.113982, https://doi.org/10.1016/j.celrep.2024.113982
Autonomous activity mechanisms	After activation, CaMKIIα can remain partly active without continued Ca(^{2+})/CaM. Classical autonomy comes from T286 autophosphorylation; additional autonomy can arise from GluN2B binding and from S-nitrosylation-related mechanisms affecting synaptic residency. Autonomous activity is mechanistically distinct from ongoing Ca(^{2+})/CaM-stimulated catalysis. (brown2024studyingcamkiitools pages 1-3, rumian2023decreasednitrosylationof pages 20-25, rumian2024ltpexpressionmediated pages 1-3)	2024 work showed that GluN2B-bound CaMKII provides the autonomous enzymatic activity needed for an early LTP expression phase, whereas CaM-competitive inhibitors do not block this already autonomous state. 2023 work showed that loss of nitrosylation causes aging-like plasticity defects without altering Ca(^{2+})/CaM-stimulated activity or T286-dependent autonomous activity itself. (rumian2023decreasednitrosylationof pages 1-3, rumian2024ltpexpressionmediated pages 1-3, rumian2024ltpexpressionmediated pages 20-24)	T286-generated autonomous activity is ~20-40% of maximal activity. LTP phases resolved in 2024: induction depends on the first ~5 min, expression on ~first 15 min, and maintenance beyond ~15 min no longer requires enzymatic CaMKII activity. (brown2024studyingcamkiitools pages 1-3, rumian2024ltpexpressionmediated pages 1-3, rumian2024ltpexpressionmediated pages 20-24)	Brown & Bayer, Cell Reports (Apr 2024), doi:10.1016/j.celrep.2024.113982, https://doi.org/10.1016/j.celrep.2024.113982; Rumian et al., Science Signaling (Jul 2023), doi:10.1126/scisignal.ade5892, https://doi.org/10.1126/scisignal.ade5892; Rumian et al., Cell Reports (Oct 2024), doi:10.1016/j.celrep.2024.114866, https://doi.org/10.1016/j.celrep.2024.114866
PTMs (T286, nitrosylation)	T286 autophosphorylation is the canonical activating PTM linked to autonomous activity and synaptic plasticity. S-nitrosylation of regulatory-domain cysteines promotes basal synaptic accumulation via GluN2B binding and supports memory/LTP; aging is associated with hypo-nitrosylation. Oxidation appeared minimal in the cited 2023 mouse study. (rumian2023decreasednitrosylationof pages 20-25, rumian2023decreasednitrosylationof pages 6-7, rumian2023decreasednitrosylationof pages 1-3)	2023 mouse knock-in work (CaMKIIΔSNO) showed that abolishing nitrosylation/oxidation-competent cysteines recapitulates aging-like deficits in memory and TBS-LTP and lowers synaptic CaMKII. The 2024 LTP study further separated pT286-dependent induction from GluN2B-bound autonomous activity required for expression. (rumian2023decreasednitrosylationof pages 20-25, rumian2023decreasednitrosylationof pages 16-20, rumian2024ltpexpressionmediated pages 3-5)	~12% of holoenzymes were nitrosylated in young-adult hippocampus; NO donor 300 μM DEA-NONOate increased synaptic CaMKII in WT neurons (n=13 control, 20 NO; ****p<0.0001) but not ΔSNO neurons; TBS-LTP impaired in ΔSNO slices (n=8 WT vs 9 ΔSNO; p=0.022); RAWM p=0.012 and contextual fear p=0.007 in young adults. (rumian2023decreasednitrosylationof pages 20-25, rumian2023decreasednitrosylationof pages 6-7, rumian2023decreasednitrosylationof pages 16-20)	Rumian et al., Science Signaling (Jul 2023), doi:10.1126/scisignal.ade5892, https://doi.org/10.1126/scisignal.ade5892; Rumian et al., Cell Reports (Oct 2024), doi:10.1016/j.celrep.2024.114866, https://doi.org/10.1016/j.celrep.2024.114866
Subcellular localization/complexes (PSD, GluN2B)	CaMKIIα is highly enriched at excitatory synapses and the postsynaptic density (PSD), where it binds the NMDA receptor subunit GluN2B. This anchoring localizes signaling to stimulated synapses and links Ca(^{2+}) entry to AMPAR trapping, SynGAP displacement, and postsynaptic reorganization. (rumian2024ltpexpressionmediated pages 20-24, rumian2024ltpexpressionmediated pages 6-8, rumian2023decreasednitrosylationof pages 13-14)	2024 work showed that GluN2B binding is structurally required for LTP induction and provides the localized autonomous kinase activity used during early expression; beyond ~15 min, structural persistence may be sufficient for maintenance. 2023 work linked nitrosylation to basal synaptic accumulation through the same GluN2B interaction. (rumian2023decreasednitrosylationof pages 20-25, rumian2024ltpexpressionmediated pages 20-24, rumian2024ltpexpressionmediated pages 6-8)	CaMKIIα/β together were previously estimated at roughly ~9% of PSD mass in cited background literature; LTP timing in 2024 was partitioned into ~5 min induction and ~15 min expression windows. (franz2022mechanismandfunctionality pages 28-32, rumian2024ltpexpressionmediated pages 6-8)	Rumian et al., Science Signaling (Jul 2023), doi:10.1126/scisignal.ade5892, https://doi.org/10.1126/scisignal.ade5892; Rumian et al., Cell Reports (Oct 2024), doi:10.1016/j.celrep.2024.114866, https://doi.org/10.1016/j.celrep.2024.114866
In vivo substrate phosphoproteomics	Adult inducible double deletion of Camk2a/Camk2b in cortex provides current in vivo evidence for CAMK2-dependent phosphosite networks under basal conditions. Enriched functions include postsynaptic specialization, glutamatergic synapse, and postsynaptic organization. Strong candidates include SHANK3, SYNGAP1, DLGAPs, GRIN2A/B, PPP3CB, CACNA1B, and KCNQ5. (rigter2024simultaneouslossof pages 12-15, rigter2024simultaneouslossof pages 8-10, rigter2024simultaneouslossof pages 10-12)	This 2024 dataset expands substrate annotation beyond curated databases, with limited overlap to PhosphoSitePlus and many previously unreported candidate substrates. It also shows that not all CAMK2-regulated sites conform tightly to the canonical motif. (rigter2024simultaneouslossof pages 12-15, rigter2024simultaneouslossof pages 10-12)	Tamoxifen 0.1 mg/g for 4 consecutive days; tissues collected 21 days later; CAMK2A/B reduced to <10% by western blot and to ~12%/~19% of control by proteomics; 208 phosphopeptides from 130 proteins downregulated >1.5-fold; T286 and S314 decreased by ~80%, while some sites such as S275/T333 decreased by ~50%. (rigter2024simultaneouslossof pages 5-8, rigter2024simultaneouslossof pages 15-17, rigter2024simultaneouslossof pages 12-15)	Rigter et al., bioRxiv (Nov 2024), doi:10.1101/2024.11.17.624016, https://doi.org/10.1101/2024.11.17.624016
Pharmacological inhibitor classes & caveats	2024 expert consensus distinguishes three major inhibitor classes: CaM-competitive inhibitors (e.g., KN62/KN93), T-site/peptide inhibitors (e.g., tatCN21, tatCN19o, AIP-derived tools), and ATP-competitive inhibitors (e.g., AS283, AS397, ruxolitinib, GS-680). These classes differ in whether they block Ca(^{2+})/CaM-stimulated activity, autonomous activity, or GluN2B binding-related functions. Off-targets and assay context are major concerns. (brown2024studyingcamkiitools pages 6-8, brown2024studyingcamkiitools pages 4-6, brown2024studyingcamkiitools pages 24-26)	2024 LTP work used these mechanistic differences to show that post-induction LTP expression depends on autonomous GluN2B-bound CaMKII activity: KN93 had no post-induction effect, whereas tatCN21 and ATP-competitive inhibitors could reverse LTP in the early post-induction window. Brown & Bayer recommend using multiple inhibitor classes rather than a single pharmacological probe. (rumian2024ltpexpressionmediated pages 3-5, rumian2024ltpexpressionmediated pages 20-24, brown2024studyingcamkiitools pages 6-8)	Suggested starting concentrations in cells/slices: 10 μM KN93, 5 μM tatCN21, 10 μM AS283/AS397/ruxolitinib-class agents; minimum ~2 μM for tatCN19o. 5 μM tatCN21 prevented CaMKII-GluN2B interaction required for LTP induction, whereas 20 μM was needed to disrupt preformed interactions. Cellular ATP is ~4 mM, so biochemical IC50 values may underestimate needed intracellular doses. (brown2024studyingcamkiitools pages 8-9, brown2024studyingcamkiitools pages 6-8)	Brown & Bayer, Cell Reports (Apr 2024), doi:10.1016/j.celrep.2024.113982, https://doi.org/10.1016/j.celrep.2024.113982; Rumian et al., Cell Reports (Oct 2024), doi:10.1016/j.celrep.2024.114866, https://doi.org/10.1016/j.celrep.2024.114866
Optogenetic tools (paCaMKII/paAIP2)	paCaMKII is a LOV2-based photoactivatable CaMKIIα engineered for direct light control of CaMKII signaling at single spines; paAIP2 is a light-gated inhibitory tool that exposes an inhibitory peptide upon illumination. These tools enable high spatial and temporal precision for testing CaMKII sufficiency or necessity in synaptic plasticity. (nagasawa2023lov2basedphotoactivatablecamkii pages 1-2, brown2024studyingcamkiitools pages 11-13, brown2024studyingcamkiitools pages 24-26)	The 2023 review describes “local optogenetics” with paCaMKII in single dendritic spines and in vivo cortex. Brown & Bayer (2024) place paCaMKII and paAIP2 within a broader toolkit for CaMKII measurement/manipulation, noting important caveats such as residual Ca(^{2+})/CaM responsiveness of paCaMKII. (nagasawa2023lov2basedphotoactivatablecamkii pages 6-8, brown2024studyingcamkiitools pages 11-13, brown2024studyingcamkiitools pages 21-24, brown2024studyingcamkiitools pages 24-26)	LOV2 deactivation half-time ~40 s (tunable); two-photon excitation volume ~1.5 μm; example activation protocols include 900 nm, 30 pulses, 1 Hz, 80 ms/pulse, 4 mW or 820 nm, 30 pulses, 0.5 Hz, 80 ms/pulse, 4 mW; spine enlargement relaxed to ~150% at 20-30 min and structural LTP persisted >4 h. (nagasawa2023lov2basedphotoactivatablecamkii pages 1-2, nagasawa2023lov2basedphotoactivatablecamkii pages 6-8, nagasawa2023lov2basedphotoactivatablecamkii pages 4-6)	Nagasawa et al., Biophysics and Physicobiology (Jun 2023), doi:10.2142/biophysico.bppb-v20.0027, https://doi.org/10.2142/biophysico.bppb-v20.0027; Brown & Bayer, Cell Reports (Apr 2024), doi:10.1016/j.celrep.2024.113982, https://doi.org/10.1016/j.celrep.2024.113982
Camk2a-Cre applications	Camk2a promoter/Cre systems are widely used to target forebrain excitatory neurons, especially hippocampal and cortical pyramidal neurons, for conditional genetics, viral expression, imaging, and chemogenetics. This is an application of the Camk2a regulatory program rather than a direct molecular function of CaMKIIα protein. (liu2024kat6adeficiencyimpairs pages 2-3, zhang2024increasedghsr1aexpression pages 2-4, sarrazin2024prefrontalcortexmolecular pages 1-2)	2024 studies used Camk2a-Cre or Camk2a promoter AAVs for postnatal excitatory-neuron gene deletion, dorsal CA1 receptor overexpression, DREADD co-expression, and mPFC molecular clock manipulation. These implementations show Camk2a regulatory elements are practical for neuron-type-restricted functional studies in adult mice. (liu2024kat6adeficiencyimpairs pages 2-3, zhang2024increasedghsr1aexpression pages 2-4, sarrazin2024prefrontalcortexmolecular pages 1-2, zhang2024increasedghsr1aexpression pages 1-2)	One 2024 study explicitly states that Camk2a-Cre expression starts at 2-3 weeks after birth and is restricted to forebrain excitatory neurons in hippocampus and cortex; another assessed AAV-driven expression ~4 weeks after injection in dorsal CA1 pyramidal neurons. (liu2024kat6adeficiencyimpairs pages 2-3, zhang2024increasedghsr1aexpression pages 2-4)	Liu et al., Science Advances (May 2024), doi:10.1126/sciadv.adm9326, https://doi.org/10.1126/sciadv.adm9326; Zhang et al., Communications Biology (Oct 2024), doi:10.1038/s42003-024-06914-y, https://doi.org/10.1038/s42003-024-06914-y; Sarrazin et al., Nature Communications (Aug 2024), doi:10.1038/s41467-024-51716-9, https://doi.org/10.1038/s41467-024-51716-9

Table: This table summarizes the core functional annotation of mouse Camk2a/CaMKIIα (UniProt P11798), integrating mechanism, regulation, localization, recent 2023-2024 findings, applications, and quantitative evidence. It is useful as a compact evidence map for interpreting CaMKIIα biology in mouse neurons.

Key references (URLs and publication dates)

Brown CN, Bayer KU. Studying CaMKII: Tools and standards. Cell Reports Apr 2024. https://doi.org/10.1016/j.celrep.2024.113982 (brown2024studyingcamkiitools pages 1-3)
Rumian NL et al. Decreased nitrosylation of CaMKII causes aging-associated impairments in memory and synaptic plasticity in mice. Science Signaling Jul 2023. https://doi.org/10.1126/scisignal.ade5892 (rumian2023decreasednitrosylationof pages 1-3)
Rumian NL et al. LTP expression mediated by autonomous activity of GluN2B-bound CaMKII. Cell Reports Oct 2024. https://doi.org/10.1016/j.celrep.2024.114866 (rumian2024ltpexpressionmediated pages 1-3)
Rigter PMF et al. Simultaneous loss of CAMK2A and CAMK2B reveals endogenous in vivo substrates. bioRxiv Nov 2024. https://doi.org/10.1101/2024.11.17.624016 (rigter2024simultaneouslossof pages 5-8)
Nagasawa Y et al. LOV2-based photoactivatable CaMKII and its application to single synapses: Local Optogenetics. Biophysics and Physicobiology Jun 2023. https://doi.org/10.2142/biophysico.bppb-v20.0027 (nagasawa2023lov2basedphotoactivatablecamkii pages 1-2)
Liu Y et al. KAT6A deficiency impairs cognitive functions through suppressing RSPO2/Wnt signaling in hippocampal CA3. Science Advances May 2024. https://doi.org/10.1126/sciadv.adm9326 (liu2024kat6adeficiencyimpairs pages 2-3)
Zhang M et al. Increased GHS-R1a expression in the hippocampus impairs memory encoding and contributes to AD-associated memory deficits. Communications Biology Oct 2024. https://doi.org/10.1038/s42003-024-06914-y (zhang2024increasedghsr1aexpression pages 2-4)
Sarrazin DH et al. Prefrontal cortex molecular clock modulates development of depression-like phenotype and rapid antidepressant response in mice. Nature Communications Aug 2024. https://doi.org/10.1038/s41467-024-51716-9 (sarrazin2024prefrontalcortexmolecular pages 1-2)

References

(rigter2024simultaneouslossof pages 5-8): Pomme M.F. Rigter, Karel Bezstarosti, Oguz Can Koc, Tyler L. Perfitt, Jeroen A.A. Demmers, Roger J. Colbran, Margaret Stratton, Ype Elgersma, and Geeske M. van Woerden. Simultaneous loss of camk2a and camk2b reveals endogenous in vivo substrates. bioRxiv, Nov 2024. URL: https://doi.org/10.1101/2024.11.17.624016, doi:10.1101/2024.11.17.624016. This article has 0 citations.
(brown2024studyingcamkiitools pages 1-3): Carolyn Nicole Brown and Karl Ulrich Bayer. Studying camkii: tools and standards. Cell Reports, 43:113982, Apr 2024. URL: https://doi.org/10.1016/j.celrep.2024.113982, doi:10.1016/j.celrep.2024.113982. This article has 39 citations and is from a highest quality peer-reviewed journal.
(brown2024studyingcamkiitools media 3753eb15): Carolyn Nicole Brown and Karl Ulrich Bayer. Studying camkii: tools and standards. Cell Reports, 43:113982, Apr 2024. URL: https://doi.org/10.1016/j.celrep.2024.113982, doi:10.1016/j.celrep.2024.113982. This article has 39 citations and is from a highest quality peer-reviewed journal.
(rumian2024ltpexpressionmediated pages 3-5): Nicole L. Rumian, C. Madison Barker, Matthew E. Larsen, Jonathan E. Tullis, Ronald K. Freund, Amir Taslimi, Steven J. Coultrap, Chandra L. Tucker, Mark L. Dell’Acqua, and K. Ulrich Bayer. Ltp expression mediated by autonomous activity of glun2b-bound camkii. Cell reports, 43:114866-114866, Oct 2024. URL: https://doi.org/10.1016/j.celrep.2024.114866, doi:10.1016/j.celrep.2024.114866. This article has 28 citations and is from a highest quality peer-reviewed journal.
(rumian2023decreasednitrosylationof pages 1-3): Nicole L. Rumian, Ronald K. Freund, Mark L. Dell’Acqua, Steven J. Coultrap, and K. Ulrich Bayer. Decreased nitrosylation of camkii causes aging-associated impairments in memory and synaptic plasticity in mice. Science Signaling, Jul 2023. URL: https://doi.org/10.1126/scisignal.ade5892, doi:10.1126/scisignal.ade5892. This article has 18 citations and is from a domain leading peer-reviewed journal.
(rumian2023decreasednitrosylationof pages 20-25): Nicole L. Rumian, Ronald K. Freund, Mark L. Dell’Acqua, Steven J. Coultrap, and K. Ulrich Bayer. Decreased nitrosylation of camkii causes aging-associated impairments in memory and synaptic plasticity in mice. Science Signaling, Jul 2023. URL: https://doi.org/10.1126/scisignal.ade5892, doi:10.1126/scisignal.ade5892. This article has 18 citations and is from a domain leading peer-reviewed journal.
(rumian2024ltpexpressionmediated pages 20-24): Nicole L. Rumian, C. Madison Barker, Matthew E. Larsen, Jonathan E. Tullis, Ronald K. Freund, Amir Taslimi, Steven J. Coultrap, Chandra L. Tucker, Mark L. Dell’Acqua, and K. Ulrich Bayer. Ltp expression mediated by autonomous activity of glun2b-bound camkii. Cell reports, 43:114866-114866, Oct 2024. URL: https://doi.org/10.1016/j.celrep.2024.114866, doi:10.1016/j.celrep.2024.114866. This article has 28 citations and is from a highest quality peer-reviewed journal.
(rumian2024ltpexpressionmediated pages 6-8): Nicole L. Rumian, C. Madison Barker, Matthew E. Larsen, Jonathan E. Tullis, Ronald K. Freund, Amir Taslimi, Steven J. Coultrap, Chandra L. Tucker, Mark L. Dell’Acqua, and K. Ulrich Bayer. Ltp expression mediated by autonomous activity of glun2b-bound camkii. Cell reports, 43:114866-114866, Oct 2024. URL: https://doi.org/10.1016/j.celrep.2024.114866, doi:10.1016/j.celrep.2024.114866. This article has 28 citations and is from a highest quality peer-reviewed journal.
(rigter2024simultaneouslossof pages 3-5): Pomme M.F. Rigter, Karel Bezstarosti, Oguz Can Koc, Tyler L. Perfitt, Jeroen A.A. Demmers, Roger J. Colbran, Margaret Stratton, Ype Elgersma, and Geeske M. van Woerden. Simultaneous loss of camk2a and camk2b reveals endogenous in vivo substrates. bioRxiv, Nov 2024. URL: https://doi.org/10.1101/2024.11.17.624016, doi:10.1101/2024.11.17.624016. This article has 0 citations.
(rigter2024simultaneouslossof pages 15-17): Pomme M.F. Rigter, Karel Bezstarosti, Oguz Can Koc, Tyler L. Perfitt, Jeroen A.A. Demmers, Roger J. Colbran, Margaret Stratton, Ype Elgersma, and Geeske M. van Woerden. Simultaneous loss of camk2a and camk2b reveals endogenous in vivo substrates. bioRxiv, Nov 2024. URL: https://doi.org/10.1101/2024.11.17.624016, doi:10.1101/2024.11.17.624016. This article has 0 citations.
(rigter2024simultaneouslossof pages 10-12): Pomme M.F. Rigter, Karel Bezstarosti, Oguz Can Koc, Tyler L. Perfitt, Jeroen A.A. Demmers, Roger J. Colbran, Margaret Stratton, Ype Elgersma, and Geeske M. van Woerden. Simultaneous loss of camk2a and camk2b reveals endogenous in vivo substrates. bioRxiv, Nov 2024. URL: https://doi.org/10.1101/2024.11.17.624016, doi:10.1101/2024.11.17.624016. This article has 0 citations.
(rigter2024simultaneouslossof pages 12-15): Pomme M.F. Rigter, Karel Bezstarosti, Oguz Can Koc, Tyler L. Perfitt, Jeroen A.A. Demmers, Roger J. Colbran, Margaret Stratton, Ype Elgersma, and Geeske M. van Woerden. Simultaneous loss of camk2a and camk2b reveals endogenous in vivo substrates. bioRxiv, Nov 2024. URL: https://doi.org/10.1101/2024.11.17.624016, doi:10.1101/2024.11.17.624016. This article has 0 citations.
(rigter2024simultaneouslossof pages 8-10): Pomme M.F. Rigter, Karel Bezstarosti, Oguz Can Koc, Tyler L. Perfitt, Jeroen A.A. Demmers, Roger J. Colbran, Margaret Stratton, Ype Elgersma, and Geeske M. van Woerden. Simultaneous loss of camk2a and camk2b reveals endogenous in vivo substrates. bioRxiv, Nov 2024. URL: https://doi.org/10.1101/2024.11.17.624016, doi:10.1101/2024.11.17.624016. This article has 0 citations.
(rumian2023decreasednitrosylationof pages 6-7): Nicole L. Rumian, Ronald K. Freund, Mark L. Dell’Acqua, Steven J. Coultrap, and K. Ulrich Bayer. Decreased nitrosylation of camkii causes aging-associated impairments in memory and synaptic plasticity in mice. Science Signaling, Jul 2023. URL: https://doi.org/10.1126/scisignal.ade5892, doi:10.1126/scisignal.ade5892. This article has 18 citations and is from a domain leading peer-reviewed journal.
(rumian2023decreasednitrosylationof pages 16-20): Nicole L. Rumian, Ronald K. Freund, Mark L. Dell’Acqua, Steven J. Coultrap, and K. Ulrich Bayer. Decreased nitrosylation of camkii causes aging-associated impairments in memory and synaptic plasticity in mice. Science Signaling, Jul 2023. URL: https://doi.org/10.1126/scisignal.ade5892, doi:10.1126/scisignal.ade5892. This article has 18 citations and is from a domain leading peer-reviewed journal.
(brown2024studyingcamkiitools pages 4-6): Carolyn Nicole Brown and Karl Ulrich Bayer. Studying camkii: tools and standards. Cell Reports, 43:113982, Apr 2024. URL: https://doi.org/10.1016/j.celrep.2024.113982, doi:10.1016/j.celrep.2024.113982. This article has 39 citations and is from a highest quality peer-reviewed journal.
(brown2024studyingcamkiitools pages 8-9): Carolyn Nicole Brown and Karl Ulrich Bayer. Studying camkii: tools and standards. Cell Reports, 43:113982, Apr 2024. URL: https://doi.org/10.1016/j.celrep.2024.113982, doi:10.1016/j.celrep.2024.113982. This article has 39 citations and is from a highest quality peer-reviewed journal.
(brown2024studyingcamkiitools pages 6-8): Carolyn Nicole Brown and Karl Ulrich Bayer. Studying camkii: tools and standards. Cell Reports, 43:113982, Apr 2024. URL: https://doi.org/10.1016/j.celrep.2024.113982, doi:10.1016/j.celrep.2024.113982. This article has 39 citations and is from a highest quality peer-reviewed journal.
(nagasawa2023lov2basedphotoactivatablecamkii pages 1-2): Yutaro Nagasawa, Hiromi H. Ueda, Haruka Kawabata, and Hideji Murakoshi. Lov2-based photoactivatable camkii and its application to single synapses: local optogenetics. Biophysics and Physicobiology, 20:n/a, Jun 2023. URL: https://doi.org/10.2142/biophysico.bppb-v20.0027, doi:10.2142/biophysico.bppb-v20.0027. This article has 3 citations.
(nagasawa2023lov2basedphotoactivatablecamkii pages 6-8): Yutaro Nagasawa, Hiromi H. Ueda, Haruka Kawabata, and Hideji Murakoshi. Lov2-based photoactivatable camkii and its application to single synapses: local optogenetics. Biophysics and Physicobiology, 20:n/a, Jun 2023. URL: https://doi.org/10.2142/biophysico.bppb-v20.0027, doi:10.2142/biophysico.bppb-v20.0027. This article has 3 citations.
(brown2024studyingcamkiitools pages 24-26): Carolyn Nicole Brown and Karl Ulrich Bayer. Studying camkii: tools and standards. Cell Reports, 43:113982, Apr 2024. URL: https://doi.org/10.1016/j.celrep.2024.113982, doi:10.1016/j.celrep.2024.113982. This article has 39 citations and is from a highest quality peer-reviewed journal.
(liu2024kat6adeficiencyimpairs pages 2-3): Yongqing Liu, Minghua Fan, Junhua Yang, Ljubica Mihaljević, Kevin Hong Chen, Yingzhi Ye, Shuying Sun, and Zhaozhu Qiu. Kat6a deficiency impairs cognitive functions through suppressing rspo2/wnt signaling in hippocampal ca3. Science Advances, May 2024. URL: https://doi.org/10.1126/sciadv.adm9326, doi:10.1126/sciadv.adm9326. This article has 16 citations and is from a highest quality peer-reviewed journal.
(zhang2024increasedghsr1aexpression pages 2-4): Meng Zhang, Liu Yang, Jiajia Jia, Fenghua Xu, Shanshan Gao, Fubing Han, Mingru Deng, Jiwei Wang, Vincent Li, Ming Yu, Yuxiang Sun, Haicheng Yuan, Yu Zhou, and Nan Li. Increased ghs-r1a expression in the hippocampus impairs memory encoding and contributes to ad-associated memory deficits. Communications Biology, Oct 2024. URL: https://doi.org/10.1038/s42003-024-06914-y, doi:10.1038/s42003-024-06914-y. This article has 6 citations and is from a peer-reviewed journal.
(rumian2024ltpexpressionmediated pages 1-3): Nicole L. Rumian, C. Madison Barker, Matthew E. Larsen, Jonathan E. Tullis, Ronald K. Freund, Amir Taslimi, Steven J. Coultrap, Chandra L. Tucker, Mark L. Dell’Acqua, and K. Ulrich Bayer. Ltp expression mediated by autonomous activity of glun2b-bound camkii. Cell reports, 43:114866-114866, Oct 2024. URL: https://doi.org/10.1016/j.celrep.2024.114866, doi:10.1016/j.celrep.2024.114866. This article has 28 citations and is from a highest quality peer-reviewed journal.
(rumian2023decreasednitrosylationof pages 13-14): Nicole L. Rumian, Ronald K. Freund, Mark L. Dell’Acqua, Steven J. Coultrap, and K. Ulrich Bayer. Decreased nitrosylation of camkii causes aging-associated impairments in memory and synaptic plasticity in mice. Science Signaling, Jul 2023. URL: https://doi.org/10.1126/scisignal.ade5892, doi:10.1126/scisignal.ade5892. This article has 18 citations and is from a domain leading peer-reviewed journal.
(franz2022mechanismandfunctionality pages 28-32): Andreas Franz. Mechanism and functionality of species-specific camk2ß alternative splicing. Text, Jan 2022. URL: https://doi.org/10.17169/refubium-35214, doi:10.17169/refubium-35214. This article has 0 citations and is from a peer-reviewed journal.
(brown2024studyingcamkiitools pages 11-13): Carolyn Nicole Brown and Karl Ulrich Bayer. Studying camkii: tools and standards. Cell Reports, 43:113982, Apr 2024. URL: https://doi.org/10.1016/j.celrep.2024.113982, doi:10.1016/j.celrep.2024.113982. This article has 39 citations and is from a highest quality peer-reviewed journal.
(brown2024studyingcamkiitools pages 21-24): Carolyn Nicole Brown and Karl Ulrich Bayer. Studying camkii: tools and standards. Cell Reports, 43:113982, Apr 2024. URL: https://doi.org/10.1016/j.celrep.2024.113982, doi:10.1016/j.celrep.2024.113982. This article has 39 citations and is from a highest quality peer-reviewed journal.
(nagasawa2023lov2basedphotoactivatablecamkii pages 4-6): Yutaro Nagasawa, Hiromi H. Ueda, Haruka Kawabata, and Hideji Murakoshi. Lov2-based photoactivatable camkii and its application to single synapses: local optogenetics. Biophysics and Physicobiology, 20:n/a, Jun 2023. URL: https://doi.org/10.2142/biophysico.bppb-v20.0027, doi:10.2142/biophysico.bppb-v20.0027. This article has 3 citations.
(sarrazin2024prefrontalcortexmolecular pages 1-2): David H. Sarrazin, Wilf Gardner, Carole Marchese, Martin Balzinger, Chockalingam Ramanathan, Marion Schott, Stanislav Rozov, Maxime Veleanu, Stefan Vestring, Claus Normann, Tomi Rantamäki, Benedicte Antoine, Michel Barrot, Etienne Challet, Patrice Bourgin, and Tsvetan Serchov. Prefrontal cortex molecular clock modulates development of depression-like phenotype and rapid antidepressant response in mice. Nature Communications, Aug 2024. URL: https://doi.org/10.1038/s41467-024-51716-9, doi:10.1038/s41467-024-51716-9. This article has 40 citations and is from a highest quality peer-reviewed journal.
(zhang2024increasedghsr1aexpression pages 1-2): Meng Zhang, Liu Yang, Jiajia Jia, Fenghua Xu, Shanshan Gao, Fubing Han, Mingru Deng, Jiwei Wang, Vincent Li, Ming Yu, Yuxiang Sun, Haicheng Yuan, Yu Zhou, and Nan Li. Increased ghs-r1a expression in the hippocampus impairs memory encoding and contributes to ad-associated memory deficits. Communications Biology, Oct 2024. URL: https://doi.org/10.1038/s42003-024-06914-y, doi:10.1038/s42003-024-06914-y. This article has 6 citations and is from a peer-reviewed journal.

Citations

rigter2024simultaneouslossof pages 5-8
brown2024studyingcamkiitools pages 1-3
rumian2023decreasednitrosylationof pages 1-3
rumian2023decreasednitrosylationof pages 20-25
rumian2024ltpexpressionmediated pages 6-8
rumian2024ltpexpressionmediated pages 20-24
rigter2024simultaneouslossof pages 10-12
brown2024studyingcamkiitools pages 4-6
brown2024studyingcamkiitools pages 24-26
rumian2023decreasednitrosylationof pages 16-20
rumian2024ltpexpressionmediated pages 1-3
sarrazin2024prefrontalcortexmolecular pages 1-2
rumian2024ltpexpressionmediated pages 3-5
rigter2024simultaneouslossof pages 3-5
rigter2024simultaneouslossof pages 15-17
rigter2024simultaneouslossof pages 12-15
rigter2024simultaneouslossof pages 8-10
rumian2023decreasednitrosylationof pages 6-7
brown2024studyingcamkiitools pages 8-9
brown2024studyingcamkiitools pages 6-8
rumian2023decreasednitrosylationof pages 13-14
franz2022mechanismandfunctionality pages 28-32
brown2024studyingcamkiitools pages 11-13
brown2024studyingcamkiitools pages 21-24
https://doi.org/10.1016/j.celrep.2024.113982;
https://doi.org/10.1101/2024.11.17.624016
https://doi.org/10.1016/j.celrep.2024.113982
https://doi.org/10.1126/scisignal.ade5892;
https://doi.org/10.1016/j.celrep.2024.114866
https://doi.org/10.2142/biophysico.bppb-v20.0027;
https://doi.org/10.1126/sciadv.adm9326;
https://doi.org/10.1038/s42003-024-06914-y;
https://doi.org/10.1038/s41467-024-51716-9
https://doi.org/10.1126/scisignal.ade5892
https://doi.org/10.2142/biophysico.bppb-v20.0027
https://doi.org/10.1126/sciadv.adm9326
https://doi.org/10.1038/s42003-024-06914-y
https://doi.org/10.1101/2024.11.17.624016,
https://doi.org/10.1016/j.celrep.2024.113982,
https://doi.org/10.1016/j.celrep.2024.114866,
https://doi.org/10.1126/scisignal.ade5892,
https://doi.org/10.2142/biophysico.bppb-v20.0027,
https://doi.org/10.1126/sciadv.adm9326,
https://doi.org/10.1038/s42003-024-06914-y,
https://doi.org/10.17169/refubium-35214,
https://doi.org/10.1038/s41467-024-51716-9,

📄 View Raw YAML

id: P11798
gene_symbol: Camk2a
product_type: PROTEIN
status: COMPLETE
taxon:
  id: NCBITaxon:10090
  label: Mus musculus
description: Calcium/calmodulin-dependent protein kinase type II alpha subunit 
  (CaMKIIα). 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:
  - term:
      id: GO:0004683
      label: calcium/calmodulin-dependent protein kinase activity
    evidence_type: IBA
    original_reference_id: GO_REF:0000033
    review:
      summary: Core kinase function
      action: ACCEPT
      reason: Essential CaMKII activity
      supported_by:
        - reference_id: UniProt:P11798
          supporting_text: "FUNCTION: Calcium/calmodulin-dependent protein kinase
            that functions autonomously after Ca(2+)/calmodulin-binding and autophosphorylation"
  - term:
      id: GO:0005737
      label: cytoplasm
    evidence_type: IBA
    original_reference_id: GO_REF:0000033
    review:
      summary: cytoplasm
      action: KEEP_AS_NON_CORE
      reason: Specialized cellular process
      supported_by:
        - reference_id: UniProt:P11798
          supporting_text: "SUBCELLULAR LOCATION:"
  - term:
      id: GO:0014069
      label: postsynaptic density
    evidence_type: IBA
    original_reference_id: GO_REF:0000033
    review:
      summary: Synaptic/neuronal function
      action: ACCEPT
      reason: Essential for CaMKII function
      supported_by:
        - reference_id: UniProt:P11798
          supporting_text: "GO; GO:0014069; C:postsynaptic density; IDA:MGI."
  - term:
      id: GO:0048168
      label: regulation of neuronal synaptic plasticity
    evidence_type: IBA
    original_reference_id: GO_REF:0000033
    review:
      summary: Synaptic/neuronal function
      action: ACCEPT
      reason: Essential for CaMKII function
      supported_by:
        - reference_id: UniProt:P11798
          supporting_text: "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"
  - term:
      id: GO:1903076
      label: regulation of protein localization to plasma membrane
    evidence_type: IBA
    original_reference_id: GO_REF:0000033
    review:
      summary: Synaptic/neuronal function
      action: KEEP_AS_NON_CORE
      reason: Important tissue-specific function
  - term:
      id: GO:0043005
      label: neuron projection
    evidence_type: IBA
    original_reference_id: GO_REF:0000033
    review:
      summary: Synaptic/neuronal function
      action: KEEP_AS_NON_CORE
      reason: Important tissue-specific function
  - term:
      id: GO:0005516
      label: calmodulin binding
    evidence_type: IBA
    original_reference_id: GO_REF:0000033
    review:
      summary: Core kinase function
      action: ACCEPT
      reason: Essential CaMKII activity
      supported_by:
        - reference_id: UniProt:P11798
          supporting_text: "GO; GO:0005516; F:calmodulin binding; IDA:CAFA."
  - term:
      id: GO:0000082
      label: G1/S transition of mitotic cell cycle
    evidence_type: IEA
    original_reference_id: GO_REF:0000117
    review:
      summary: G1/S transition of mitotic cell cycle
      action: KEEP_AS_NON_CORE
      reason: Specialized cellular process
  - term:
      id: GO:0000166
      label: nucleotide binding
    evidence_type: IEA
    original_reference_id: GO_REF:0000043
    review:
      summary: Non-specific term
      action: MARK_AS_OVER_ANNOTATED
      reason: Term is too general and uninformative
  - term:
      id: GO:0004672
      label: protein kinase activity
    evidence_type: IEA
    original_reference_id: GO_REF:0000002
    review:
      summary: protein kinase activity
      action: KEEP_AS_NON_CORE
      reason: Specialized cellular process
  - term:
      id: GO:0004674
      label: protein serine/threonine kinase activity
    evidence_type: IEA
    original_reference_id: GO_REF:0000043
    review:
      summary: Core kinase function
      action: ACCEPT
      reason: Essential CaMKII activity
  - term:
      id: GO:0004683
      label: calcium/calmodulin-dependent protein kinase activity
    evidence_type: IEA
    original_reference_id: GO_REF:0000120
    review:
      summary: Core kinase function
      action: ACCEPT
      reason: Essential CaMKII activity
  - term:
      id: GO:0005516
      label: calmodulin binding
    evidence_type: IEA
    original_reference_id: GO_REF:0000120
    review:
      summary: Core kinase function
      action: ACCEPT
      reason: Essential CaMKII activity
  - term:
      id: GO:0005524
      label: ATP binding
    evidence_type: IEA
    original_reference_id: GO_REF:0000120
    review:
      summary: Core kinase function
      action: ACCEPT
      reason: Essential CaMKII activity
      supported_by:
        - reference_id: UniProt:P11798
          supporting_text: "GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW."
  - term:
      id: GO:0005737
      label: cytoplasm
    evidence_type: IEA
    original_reference_id: GO_REF:0000044
    review:
      summary: cytoplasm
      action: KEEP_AS_NON_CORE
      reason: Specialized cellular process
  - term:
      id: GO:0006816
      label: calcium ion transport
    evidence_type: IEA
    original_reference_id: GO_REF:0000117
    review:
      summary: calcium ion transport
      action: KEEP_AS_NON_CORE
      reason: Specialized cellular process
  - term:
      id: GO:0014069
      label: postsynaptic density
    evidence_type: IEA
    original_reference_id: GO_REF:0000044
    review:
      summary: Synaptic/neuronal function
      action: ACCEPT
      reason: Essential for CaMKII function
  - term:
      id: GO:0016301
      label: kinase activity
    evidence_type: IEA
    original_reference_id: GO_REF:0000043
    review:
      summary: Core kinase function
      action: ACCEPT
      reason: Essential CaMKII activity
  - term:
      id: GO:0016740
      label: transferase activity
    evidence_type: IEA
    original_reference_id: GO_REF:0000043
    review:
      summary: Core kinase function
      action: ACCEPT
      reason: Defines essential CaMKII catalytic activity
  - term:
      id: GO:0030425
      label: dendrite
    evidence_type: IEA
    original_reference_id: GO_REF:0000044
    review:
      summary: Core neuronal localization/function
      action: ACCEPT
      reason: Essential for CaMKIIα neuronal role
      supported_by:
        - reference_id: UniProt:P11798
          supporting_text: Regulates dendritic spine development (By 
            similarity).
  - term:
      id: GO:0043197
      label: dendritic spine
    evidence_type: IEA
    original_reference_id: GO_REF:0000044
    review:
      summary: Core neuronal localization/function
      action: ACCEPT
      reason: Essential for CaMKIIα neuronal role
      supported_by:
        - reference_id: UniProt:P11798
          supporting_text: "GO; GO:0043197; C:dendritic spine; ISS:UniProtKB."
  - term:
      id: GO:0043226
      label: organelle
    evidence_type: IEA
    original_reference_id: GO_REF:0000117
    review:
      summary: Non-specific term
      action: MARK_AS_OVER_ANNOTATED
      reason: Term is too general and uninformative
  - term:
      id: GO:0045202
      label: synapse
    evidence_type: IEA
    original_reference_id: GO_REF:0000044
    review:
      summary: Core neuronal localization/function
      action: ACCEPT
      reason: Essential for CaMKIIα neuronal role
  - term:
      id: GO:0046872
      label: metal ion binding
    evidence_type: IEA
    original_reference_id: GO_REF:0000043
    review:
      summary: Non-specific term
      action: MARK_AS_OVER_ANNOTATED
      reason: Term is too general and uninformative
  - term:
      id: GO:0106310
      label: protein serine kinase activity
    evidence_type: IEA
    original_reference_id: GO_REF:0000116
    review:
      summary: Core kinase function
      action: ACCEPT
      reason: Defines essential CaMKII catalytic activity
  - term:
      id: GO:0005515
      label: protein binding
    evidence_type: IPI
    original_reference_id: PMID:10862698
    review:
      summary: Non-specific term
      action: MARK_AS_OVER_ANNOTATED
      reason: Term is too general and uninformative
      supported_by:
        - reference_id: PMID:10862698
          supporting_text: Proteomic analysis of NMDA receptor-adhesion protein 
            signaling complexes.
  - term:
      id: GO:0005515
      label: protein binding
    evidence_type: IPI
    original_reference_id: PMID:16120608
    review:
      summary: Non-specific term
      action: MARK_AS_OVER_ANNOTATED
      reason: Term is too general and uninformative
      supported_by:
        - reference_id: PMID:16120608
          supporting_text: 2005 Aug 24. Multivalent interactions of 
            calcium/calmodulin-dependent protein kinase II with the postsynaptic
            density proteins NR2B, densin-180, and alpha-actinin-2.
  - term:
      id: GO:0005515
      label: protein binding
    evidence_type: IPI
    original_reference_id: PMID:16710293
    review:
      summary: Non-specific term
      action: MARK_AS_OVER_ANNOTATED
      reason: Term is too general and uninformative
      supported_by:
        - reference_id: PMID:16710293
          supporting_text: May 18. NR2B tyrosine phosphorylation modulates fear 
            learning as well as amygdaloid synaptic plasticity.
  - term:
      id: GO:0005515
      label: protein binding
    evidence_type: IPI
    original_reference_id: PMID:19455133
    review:
      summary: Non-specific term
      action: MARK_AS_OVER_ANNOTATED
      reason: Term is too general and uninformative
      supported_by:
        - reference_id: PMID:19455133
          supporting_text: Targeted tandem affinity purification of PSD-95 
            recovers core postsynaptic complexes and schizophrenia 
            susceptibility proteins.
  - term:
      id: GO:0005515
      label: protein binding
    evidence_type: IPI
    original_reference_id: PMID:20141836
    review:
      summary: Non-specific term
      action: MARK_AS_OVER_ANNOTATED
      reason: Term is too general and uninformative
      supported_by:
        - reference_id: PMID:20141836
          supporting_text: DAPK1 interaction with NMDA receptor NR2B subunits 
            mediates brain damage in stroke.
  - term:
      id: GO:0005515
      label: protein binding
    evidence_type: IPI
    original_reference_id: PMID:22234183
    review:
      summary: Non-specific term
      action: MARK_AS_OVER_ANNOTATED
      reason: Term is too general and uninformative
      supported_by:
        - reference_id: PMID:22234183
          supporting_text: CaMKII binding to GluN2B is critical during memory 
            consolidation.
  - term:
      id: GO:0005515
      label: protein binding
    evidence_type: IPI
    original_reference_id: PMID:24725413
    review:
      summary: Non-specific term
      action: MARK_AS_OVER_ANNOTATED
      reason: Term is too general and uninformative
      supported_by:
        - reference_id: PMID:24725413
          supporting_text: Activity-dependent p25 generation regulates synaptic 
            plasticity and Aβ-induced cognitive impairment.
  - term:
      id: GO:0005515
      label: protein binding
    evidence_type: IPI
    original_reference_id: PMID:28130356
    review:
      summary: Non-specific term
      action: MARK_AS_OVER_ANNOTATED
      reason: Term is too general and uninformative
      supported_by:
        - reference_id: PMID:28130356
          supporting_text: Epub 2017 Jan 27. A Novel Human CAMK2A Mutation 
            Disrupts Dendritic Morphology and Synaptic Transmission, and Causes 
            ASD-Related Behaviors.
  - term:
      id: GO:0005515
      label: protein binding
    evidence_type: IPI
    original_reference_id: PMID:28671696
    review:
      summary: Non-specific term
      action: MARK_AS_OVER_ANNOTATED
      reason: Term is too general and uninformative
      supported_by:
        - reference_id: PMID:28671696
          supporting_text: Spatiotemporal profile of postsynaptic interactomes 
            integrates components of complex brain disorders.
  - term:
      id: GO:0004674
      label: protein serine/threonine kinase activity
    evidence_type: ISO
    original_reference_id: GO_REF:0000119
    review:
      summary: Core kinase function
      action: ACCEPT
      reason: Essential CaMKII activity
  - term:
      id: GO:0004683
      label: calcium/calmodulin-dependent protein kinase activity
    evidence_type: ISO
    original_reference_id: GO_REF:0000119
    review:
      summary: Core kinase function
      action: ACCEPT
      reason: Essential CaMKII activity
  - term:
      id: GO:0005516
      label: calmodulin binding
    evidence_type: ISO
    original_reference_id: GO_REF:0000119
    review:
      summary: Core kinase function
      action: ACCEPT
      reason: Essential CaMKII activity
  - term:
      id: GO:0005954
      label: calcium- and calmodulin-dependent protein kinase complex
    evidence_type: ISO
    original_reference_id: GO_REF:0000119
    review:
      summary: Core kinase function
      action: ACCEPT
      reason: Defines essential CaMKII catalytic activity
  - term:
      id: GO:0006468
      label: protein phosphorylation
    evidence_type: ISO
    original_reference_id: GO_REF:0000119
    review:
      summary: Core kinase function
      action: ACCEPT
      reason: Essential CaMKII activity
  - term:
      id: GO:0016301
      label: kinase activity
    evidence_type: ISO
    original_reference_id: GO_REF:0000119
    review:
      summary: Core kinase function
      action: ACCEPT
      reason: Essential CaMKII activity
  - term:
      id: GO:0035458
      label: cellular response to interferon-beta
    evidence_type: ISO
    original_reference_id: GO_REF:0000119
    review:
      summary: Signaling pathway involvement
      action: KEEP_AS_NON_CORE
      reason: Downstream signaling role
  - term:
      id: GO:0038166
      label: angiotensin-activated signaling pathway
    evidence_type: ISO
    original_reference_id: GO_REF:0000119
    review:
      summary: Signaling pathway involvement
      action: KEEP_AS_NON_CORE
      reason: Downstream signaling role
  - term:
      id: GO:0042802
      label: identical protein binding
    evidence_type: ISO
    original_reference_id: GO_REF:0000119
    review:
      summary: Non-specific term
      action: MARK_AS_OVER_ANNOTATED
      reason: Term is too general and uninformative
  - term:
      id: GO:0042803
      label: protein homodimerization activity
    evidence_type: ISO
    original_reference_id: GO_REF:0000119
    review:
      summary: Non-specific term
      action: MARK_AS_OVER_ANNOTATED
      reason: Term is too general and uninformative
  - term:
      id: GO:0043197
      label: dendritic spine
    evidence_type: ISO
    original_reference_id: GO_REF:0000119
    review:
      summary: Core neuronal localization/function
      action: ACCEPT
      reason: Essential for CaMKIIα neuronal role
  - term:
      id: GO:0046427
      label: positive regulation of receptor signaling pathway via JAK-STAT
    evidence_type: ISO
    original_reference_id: GO_REF:0000119
    review:
      summary: Signaling pathway involvement
      action: KEEP_AS_NON_CORE
      reason: Downstream signaling role
  - term:
      id: GO:0060996
      label: dendritic spine development
    evidence_type: ISO
    original_reference_id: GO_REF:0000119
    review:
      summary: Core neuronal localization/function
      action: ACCEPT
      reason: Essential for CaMKIIα neuronal role
  - term:
      id: GO:0071346
      label: cellular response to type II interferon
    evidence_type: ISO
    original_reference_id: GO_REF:0000119
    review:
      summary: Signaling pathway involvement
      action: KEEP_AS_NON_CORE
      reason: Downstream signaling role
  - term:
      id: GO:0110076
      label: negative regulation of ferroptosis
    evidence_type: ISO
    original_reference_id: GO_REF:0000119
    review:
      summary: negative regulation of ferroptosis
      action: KEEP_AS_NON_CORE
      reason: Specialized cellular process
  - term:
      id: GO:1990443
      label: peptidyl-threonine autophosphorylation
    evidence_type: ISO
    original_reference_id: GO_REF:0000119
    review:
      summary: Core kinase function
      action: ACCEPT
      reason: Defines essential CaMKII catalytic activity
  - term:
      id: GO:2001222
      label: regulation of neuron migration
    evidence_type: ISO
    original_reference_id: GO_REF:0000119
    review:
      summary: Synaptic/neuronal function
      action: KEEP_AS_NON_CORE
      reason: Important tissue-specific function
  - term:
      id: GO:0004674
      label: protein serine/threonine kinase activity
    evidence_type: IMP
    original_reference_id: PMID:23502535
    review:
      summary: Core kinase function
      action: ACCEPT
      reason: Essential CaMKII activity
      supported_by:
        - reference_id: PMID:23502535
          supporting_text: CaMKII regulates diacylglycerol lipase-α and striatal
            endocannabinoid signaling.
  - term:
      id: GO:0004674
      label: protein serine/threonine kinase activity
    evidence_type: IMP
    original_reference_id: PMID:28130356
    review:
      summary: Core kinase function
      action: ACCEPT
      reason: Essential CaMKII activity
      supported_by:
        - reference_id: PMID:28130356
          supporting_text: Epub 2017 Jan 27. A Novel Human CAMK2A Mutation 
            Disrupts Dendritic Morphology and Synaptic Transmission, and Causes 
            ASD-Related Behaviors.
  - term:
      id: GO:0006468
      label: protein phosphorylation
    evidence_type: ISO
    original_reference_id: GO_REF:0000096
    review:
      summary: Core kinase function
      action: ACCEPT
      reason: Essential CaMKII activity
  - term:
      id: GO:0018105
      label: peptidyl-serine phosphorylation
    evidence_type: ISO
    original_reference_id: GO_REF:0000096
    review:
      summary: Core kinase function
      action: ACCEPT
      reason: Essential CaMKII activity
  - term:
      id: GO:0046777
      label: protein autophosphorylation
    evidence_type: ISO
    original_reference_id: GO_REF:0000096
    review:
      summary: Core kinase function
      action: ACCEPT
      reason: Essential CaMKII activity
  - term:
      id: GO:0004683
      label: calcium/calmodulin-dependent protein kinase activity
    evidence_type: ISO
    original_reference_id: GO_REF:0000096
    review:
      summary: Core kinase function
      action: ACCEPT
      reason: Essential CaMKII activity
  - term:
      id: GO:0007259
      label: cell surface receptor signaling pathway via JAK-STAT
    evidence_type: ISO
    original_reference_id: GO_REF:0000119
    review:
      summary: Signaling pathway involvement
      action: KEEP_AS_NON_CORE
      reason: Downstream signaling role
  - term:
      id: GO:0014069
      label: postsynaptic density
    evidence_type: ISO
    original_reference_id: GO_REF:0000096
    review:
      summary: Synaptic/neuronal function
      action: ACCEPT
      reason: Essential for CaMKII function
  - term:
      id: GO:0030424
      label: axon
    evidence_type: ISO
    original_reference_id: GO_REF:0000096
    review:
      summary: Synaptic/neuronal function
      action: KEEP_AS_NON_CORE
      reason: Important tissue-specific function
  - term:
      id: GO:0030425
      label: dendrite
    evidence_type: ISO
    original_reference_id: GO_REF:0000096
    review:
      summary: Core neuronal localization/function
      action: ACCEPT
      reason: Essential for CaMKIIα neuronal role
  - term:
      id: GO:0032794
      label: GTPase activating protein binding
    evidence_type: ISO
    original_reference_id: GO_REF:0000096
    review:
      summary: GTPase activating protein binding
      action: KEEP_AS_NON_CORE
      reason: Specialized cellular process
  - term:
      id: GO:0032839
      label: dendrite cytoplasm
    evidence_type: ISO
    original_reference_id: GO_REF:0000096
    review:
      summary: Synaptic/neuronal function
      action: KEEP_AS_NON_CORE
      reason: Important tissue-specific function
  - term:
      id: GO:0035235
      label: ionotropic glutamate receptor signaling pathway
    evidence_type: ISO
    original_reference_id: GO_REF:0000096
    review:
      summary: Synaptic/neuronal function
      action: KEEP_AS_NON_CORE
      reason: Important tissue-specific function
  - term:
      id: GO:0043025
      label: neuronal cell body
    evidence_type: ISO
    original_reference_id: GO_REF:0000096
    review:
      summary: Synaptic/neuronal function
      action: KEEP_AS_NON_CORE
      reason: Important tissue-specific function
  - term:
      id: GO:0098696
      label: regulation of neurotransmitter receptor localization to 
        postsynaptic specialization membrane
    evidence_type: ISO
    original_reference_id: GO_REF:0000096
    review:
      summary: Synaptic/neuronal function
      action: KEEP_AS_NON_CORE
      reason: Important tissue-specific function
  - term:
      id: GO:0098877
      label: neurotransmitter receptor transport to plasma membrane
    evidence_type: ISO
    original_reference_id: GO_REF:0000096
    review:
      summary: Synaptic/neuronal function
      action: KEEP_AS_NON_CORE
      reason: Important tissue-specific function
  - term:
      id: GO:0098978
      label: glutamatergic synapse
    evidence_type: ISO
    original_reference_id: GO_REF:0000096
    review:
      summary: Synaptic/neuronal function
      action: KEEP_AS_NON_CORE
      reason: Important tissue-specific function
  - term:
      id: GO:0099523
      label: presynaptic cytosol
    evidence_type: ISO
    original_reference_id: GO_REF:0000096
    review:
      summary: Synaptic/neuronal function
      action: ACCEPT
      reason: Essential for CaMKII function
  - term:
      id: GO:0099524
      label: postsynaptic cytosol
    evidence_type: ISO
    original_reference_id: GO_REF:0000096
    review:
      summary: Synaptic/neuronal function
      action: KEEP_AS_NON_CORE
      reason: Important tissue-specific function
  - term:
      id: GO:1903076
      label: regulation of protein localization to plasma membrane
    evidence_type: ISO
    original_reference_id: GO_REF:0000096
    review:
      summary: Synaptic/neuronal function
      action: KEEP_AS_NON_CORE
      reason: Important tissue-specific function
  - term:
      id: GO:0110076
      label: negative regulation of ferroptosis
    evidence_type: ISS
    original_reference_id: GO_REF:0000024
    review:
      summary: negative regulation of ferroptosis
      action: KEEP_AS_NON_CORE
      reason: Specialized cellular process
  - term:
      id: GO:0098685
      label: Schaffer collateral - CA1 synapse
    evidence_type: IMP
    original_reference_id: PMID:17660813
    review:
      summary: Core neuronal localization/function
      action: ACCEPT
      reason: Essential for CaMKIIα neuronal role
      supported_by:
        - reference_id: PMID:17660813
          supporting_text: Kinase activity is not required for 
            alphaCaMKII-dependent presynaptic plasticity at CA3-CA1 synapses.
  - term:
      id: GO:0098685
      label: Schaffer collateral - CA1 synapse
    evidence_type: IDA
    original_reference_id: PMID:17660813
    review:
      summary: Core neuronal localization/function
      action: ACCEPT
      reason: Essential for CaMKIIα neuronal role
      supported_by:
        - reference_id: PMID:17660813
          supporting_text: Kinase activity is not required for 
            alphaCaMKII-dependent presynaptic plasticity at CA3-CA1 synapses.
  - term:
      id: GO:0099148
      label: regulation of synaptic vesicle docking
    evidence_type: IMP
    original_reference_id: PMID:17660813
    review:
      summary: Synaptic/neuronal function
      action: ACCEPT
      reason: Essential for CaMKII function
      supported_by:
        - reference_id: PMID:17660813
          supporting_text: Kinase activity is not required for 
            alphaCaMKII-dependent presynaptic plasticity at CA3-CA1 synapses.
  - term:
      id: GO:0099148
      label: regulation of synaptic vesicle docking
    evidence_type: IDA
    original_reference_id: PMID:17660813
    review:
      summary: Synaptic/neuronal function
      action: ACCEPT
      reason: Essential for CaMKII function
      supported_by:
        - reference_id: PMID:17660813
          supporting_text: Kinase activity is not required for 
            alphaCaMKII-dependent presynaptic plasticity at CA3-CA1 synapses.
  - term:
      id: GO:0035458
      label: cellular response to interferon-beta
    evidence_type: ISS
    original_reference_id: GO_REF:0000024
    review:
      summary: Signaling pathway involvement
      action: KEEP_AS_NON_CORE
      reason: Downstream signaling role
  - term:
      id: GO:0046427
      label: positive regulation of receptor signaling pathway via JAK-STAT
    evidence_type: ISS
    original_reference_id: GO_REF:0000024
    review:
      summary: Signaling pathway involvement
      action: KEEP_AS_NON_CORE
      reason: Downstream signaling role
  - term:
      id: GO:0045202
      label: synapse
    evidence_type: IDA
    original_reference_id: PMID:28642476
    review:
      summary: Core neuronal localization/function
      action: ACCEPT
      reason: Essential for CaMKIIα neuronal role
      supported_by:
        - reference_id: PMID:28642476
          supporting_text: Prevention of long-term memory loss after retrieval 
            by an endogenous CaMKII inhibitor.
  - term:
      id: GO:0048168
      label: regulation of neuronal synaptic plasticity
    evidence_type: IMP
    original_reference_id: PMID:17610578
    review:
      summary: Synaptic/neuronal function
      action: ACCEPT
      reason: Essential for CaMKII function
      supported_by:
        - reference_id: PMID:17610578
          supporting_text: 'Alpha-synuclein involvement in hippocampal synaptic plasticity:
            role of NO, cGMP, cGK and CaMKII.'
  - term:
      id: GO:1902108
      label: regulation of mitochondrial membrane permeability involved in 
        apoptotic process
    evidence_type: IMP
    original_reference_id: PMID:23051746
    review:
      summary: regulation of mitochondrial membrane per...
      action: KEEP_AS_NON_CORE
      reason: Specialized cellular process
      supported_by:
        - reference_id: PMID:23051746
          supporting_text: CaMKII determines mitochondrial stress responses in 
            heart.
  - term:
      id: GO:0005515
      label: protein binding
    evidence_type: IPI
    original_reference_id: PMID:23502535
    review:
      summary: Non-specific term
      action: MARK_AS_OVER_ANNOTATED
      reason: Term is too general and uninformative
      supported_by:
        - reference_id: PMID:23502535
          supporting_text: CaMKII regulates diacylglycerol lipase-α and striatal
            endocannabinoid signaling.
  - term:
      id: GO:2000124
      label: regulation of endocannabinoid signaling pathway
    evidence_type: IMP
    original_reference_id: PMID:23502535
    review:
      summary: Signaling pathway involvement
      action: KEEP_AS_NON_CORE
      reason: Downstream signaling role
      supported_by:
        - reference_id: PMID:23502535
          supporting_text: CaMKII regulates diacylglycerol lipase-α and striatal
            endocannabinoid signaling.
  - term:
      id: GO:0005954
      label: calcium- and calmodulin-dependent protein kinase complex
    evidence_type: ISS
    original_reference_id: GO_REF:0000024
    review:
      summary: Core kinase function
      action: ACCEPT
      reason: Defines essential CaMKII catalytic activity
  - term:
      id: GO:0043197
      label: dendritic spine
    evidence_type: ISS
    original_reference_id: GO_REF:0000024
    review:
      summary: Core neuronal localization/function
      action: ACCEPT
      reason: Essential for CaMKIIα neuronal role
  - term:
      id: GO:0060996
      label: dendritic spine development
    evidence_type: ISS
    original_reference_id: GO_REF:0000024
    review:
      summary: Core neuronal localization/function
      action: ACCEPT
      reason: Essential for CaMKIIα neuronal role
  - term:
      id: GO:2001222
      label: regulation of neuron migration
    evidence_type: ISS
    original_reference_id: GO_REF:0000024
    review:
      summary: Synaptic/neuronal function
      action: KEEP_AS_NON_CORE
      reason: Important tissue-specific function
  - term:
      id: GO:0005739
      label: mitochondrion
    evidence_type: IDA
    original_reference_id: PMID:23051746
    review:
      summary: mitochondrion
      action: KEEP_AS_NON_CORE
      reason: Specialized cellular process
      supported_by:
        - reference_id: PMID:23051746
          supporting_text: CaMKII determines mitochondrial stress responses in 
            heart.
  - term:
      id: GO:0004683
      label: calcium/calmodulin-dependent protein kinase activity
    evidence_type: IDA
    original_reference_id: PMID:15994560
    review:
      summary: Core kinase function
      action: ACCEPT
      reason: Essential CaMKII activity
      supported_by:
        - reference_id: PMID:15994560
          supporting_text: Variable control of Ets-1 DNA binding by multiple 
            phosphates in an unstructured region.
  - term:
      id: GO:0005516
      label: calmodulin binding
    evidence_type: IDA
    original_reference_id: PMID:15994560
    review:
      summary: Core kinase function
      action: ACCEPT
      reason: Essential CaMKII activity
      supported_by:
        - reference_id: PMID:15994560
          supporting_text: Variable control of Ets-1 DNA binding by multiple 
            phosphates in an unstructured region.
  - term:
      id: GO:0005515
      label: protein binding
    evidence_type: IPI
    original_reference_id: PMID:25297099
    review:
      summary: Non-specific term
      action: MARK_AS_OVER_ANNOTATED
      reason: Term is too general and uninformative
      supported_by:
        - reference_id: PMID:25297099
          supporting_text: The schizophrenia susceptibility gene dysbindin 
            regulates dendritic spine dynamics.
  - term:
      id: GO:0048813
      label: dendrite morphogenesis
    evidence_type: IMP
    original_reference_id: PMID:25297099
    review:
      summary: Core neuronal localization/function
      action: ACCEPT
      reason: Essential for CaMKIIα neuronal role
      supported_by:
        - reference_id: PMID:25297099
          supporting_text: The schizophrenia susceptibility gene dysbindin 
            regulates dendritic spine dynamics.
  - term:
      id: GO:0014069
      label: postsynaptic density
    evidence_type: IDA
    original_reference_id: PMID:17114649
    review:
      summary: Synaptic/neuronal function
      action: ACCEPT
      reason: Essential for CaMKII function
      supported_by:
        - reference_id: PMID:17114649
          supporting_text: Epub 2006 Nov 17. Qualitative and quantitative 
            analyses of protein phosphorylation in naive and stimulated mouse 
            synaptosomal preparations.
  - term:
      id: GO:0002931
      label: response to ischemia
    evidence_type: IMP
    original_reference_id: PMID:23051746
    review:
      summary: The cited heart study supports CaMKII inhibitor/activity effects but
        does not clearly distinguish Camk2a/CaMKIIalpha-specific biology.
      action: UNDECIDED
      reason: Evidence is not clearly Camk2a-specific
      supported_by:
        - reference_id: PMID:23051746
          supporting_text: CaMKII determines mitochondrial stress responses in 
            heart.
  - term:
      id: GO:0004674
      label: protein serine/threonine kinase activity
    evidence_type: IMP
    original_reference_id: PMID:23051746
    review:
      summary: The cited heart study supports CaMKII activity broadly but does not
        clearly establish Camk2a/CaMKIIalpha-specific kinase activity.
      action: UNDECIDED
      reason: Evidence is not clearly Camk2a-specific
      supported_by:
        - reference_id: PMID:23051746
          supporting_text: CaMKII determines mitochondrial stress responses in 
            heart.
  - term:
      id: GO:0010666
      label: positive regulation of cardiac muscle cell apoptotic process
    evidence_type: IMP
    original_reference_id: PMID:23051746
    review:
      summary: Cardiac apoptosis effects are from a broad CaMKII heart context and
        are not clearly Camk2a/CaMKIIalpha-specific.
      action: UNDECIDED
      reason: Evidence is not clearly Camk2a-specific
      supported_by:
        - reference_id: PMID:23051746
          supporting_text: CaMKII determines mitochondrial stress responses in 
            heart.
  - term:
      id: GO:0018105
      label: peptidyl-serine phosphorylation
    evidence_type: IMP
    original_reference_id: PMID:23051746
    review:
      summary: The cited heart study supports CaMKII activity broadly but does not
        clearly establish Camk2a/CaMKIIalpha-specific serine phosphorylation.
      action: UNDECIDED
      reason: Evidence is not clearly Camk2a-specific
      supported_by:
        - reference_id: PMID:23051746
          supporting_text: CaMKII determines mitochondrial stress responses in 
            heart.
  - term:
      id: GO:0051928
      label: positive regulation of calcium ion transport
    evidence_type: IMP
    original_reference_id: PMID:23051746
    review:
      summary: Calcium transport effects are from a broad CaMKII heart context and
        are not clearly Camk2a/CaMKIIalpha-specific.
      action: UNDECIDED
      reason: Evidence is not clearly Camk2a-specific
      supported_by:
        - reference_id: PMID:23051746
          supporting_text: CaMKII determines mitochondrial stress responses in 
            heart.
  - term:
      id: GO:0004674
      label: protein serine/threonine kinase activity
    evidence_type: IDA
    original_reference_id: PMID:18480293
    review:
      summary: Core kinase function
      action: ACCEPT
      reason: Essential CaMKII activity
      supported_by:
        - reference_id: PMID:18480293
          supporting_text: Phosphorylation of Homer3 by 
            calcium/calmodulin-dependent kinase II regulates a coupling state of
            its target molecules in Purkinje cells.
  - term:
      id: GO:0005515
      label: protein binding
    evidence_type: IPI
    original_reference_id: PMID:15140879
    review:
      summary: Non-specific term
      action: MARK_AS_OVER_ANNOTATED
      reason: Term is too general and uninformative
      supported_by:
        - reference_id: PMID:15140879
          supporting_text: 2004 Mar 31. Regulation of the multifunctional 
            Ca2+/calmodulin-dependent protein kinase II by the PP2C phosphatase 
            PPM1F in fibroblasts.
  - term:
      id: GO:0035254
      label: glutamate receptor binding
    evidence_type: IPI
    original_reference_id: PMID:16710293
    review:
      summary: GluN2B/NMDA receptor binding is a central non-catalytic synaptic
        scaffolding interaction for CaMKIIalpha.
      action: ACCEPT
      reason: Core non-catalytic CaMKIIalpha synaptic function
      supported_by:
        - reference_id: PMID:16710293
          supporting_text: May 18. NR2B tyrosine phosphorylation modulates fear 
            learning as well as amygdaloid synaptic plasticity.
        - reference_id: PMID:22234183
          supporting_text: CaMKII binding to GluN2B is critical during memory consolidation.
        - reference_id: file:mouse/Camk2a/Camk2a-deep-research-falcon.md
          supporting_text: Falcon synthesis identifies GluN2B/NMDAR binding as a
            central CaMKIIalpha structural and scaffolding function.
  - term:
      id: GO:0005515
      label: protein binding
    evidence_type: IPI
    original_reference_id: PMID:12223541
    review:
      summary: Non-specific term
      action: MARK_AS_OVER_ANNOTATED
      reason: Term is too general and uninformative
      supported_by:
        - reference_id: PMID:12223541
          supporting_text: 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.
  - term:
      id: GO:0000082
      label: G1/S transition of mitotic cell cycle
    evidence_type: IMP
    original_reference_id: PMID:12660151
    review:
      summary: The cited vascular smooth muscle study supports CaMKII activity broadly
        but does not clearly establish Camk2a/CaMKIIalpha-specific cell-cycle biology.
      action: UNDECIDED
      reason: Evidence is not clearly Camk2a-specific
      supported_by:
        - reference_id: PMID:12660151
          supporting_text: Calcineurin-independent regulation of plasma membrane
            Ca2+ ATPase-4 in the vascular smooth muscle cell cycle.
  - term:
      id: GO:0004674
      label: protein serine/threonine kinase activity
    evidence_type: IMP
    original_reference_id: PMID:12660151
    review:
      summary: The cited vascular smooth muscle study supports CaMKII activity broadly
        but does not clearly establish Camk2a/CaMKIIalpha-specific kinase activity.
      action: UNDECIDED
      reason: Evidence is not clearly Camk2a-specific
      supported_by:
        - reference_id: PMID:12660151
          supporting_text: Calcineurin-independent regulation of plasma membrane
            Ca2+ ATPase-4 in the vascular smooth muscle cell cycle.
  - term:
      id: GO:0006816
      label: calcium ion transport
    evidence_type: IMP
    original_reference_id: PMID:12660151
    review:
      summary: The cited vascular smooth muscle study is not clear evidence for a
        Camk2a-specific calcium transport annotation.
      action: UNDECIDED
      reason: Evidence is not clearly Camk2a-specific
      supported_by:
        - reference_id: PMID:12660151
          supporting_text: Calcineurin-independent regulation of plasma membrane
            Ca2+ ATPase-4 in the vascular smooth muscle cell cycle.
  - term:
      id: GO:0046777
      label: protein autophosphorylation
    evidence_type: IMP
    original_reference_id: PMID:12660151
    review:
      summary: The cited vascular smooth muscle study supports CaMKII activity broadly
        but does not clearly establish Camk2a/CaMKIIalpha-specific autophosphorylation.
      action: UNDECIDED
      reason: Evidence is not clearly Camk2a-specific
      supported_by:
        - reference_id: PMID:12660151
          supporting_text: Calcineurin-independent regulation of plasma membrane
            Ca2+ ATPase-4 in the vascular smooth muscle cell cycle.
  - term:
      id: GO:0046928
      label: regulation of neurotransmitter secretion
    evidence_type: IMP
    original_reference_id: PMID:12629219
    review:
      summary: Synaptic/neuronal function
      action: ACCEPT
      reason: Essential for CaMKII function
      supported_by:
        - reference_id: PMID:12629219
          supporting_text: Essential function of 
            alpha-calcium/calmodulin-dependent protein kinase II in 
            neurotransmitter release at a glutamatergic central synapse.
references:
  - id: GO_REF:0000002
    title: Gene Ontology annotation through association of InterPro records with
      GO terms
    findings: []
  - id: GO_REF:0000024
    title: Manual transfer of experimentally-verified manual GO annotation data 
      to orthologs by curator judgment of sequence similarity
    findings: []
  - id: GO_REF:0000033
    title: Annotation inferences using phylogenetic trees
    findings: []
  - id: GO_REF:0000043
    title: Gene Ontology annotation based on UniProtKB/Swiss-Prot keyword 
      mapping
    findings: []
  - id: GO_REF:0000044
    title: Gene Ontology annotation based on UniProtKB/Swiss-Prot Subcellular 
      Location vocabulary mapping, accompanied by conservative changes to GO 
      terms applied by UniProt
    findings: []
  - id: GO_REF:0000096
    title: Automated transfer of experimentally-verified manual GO annotation 
      data to mouse-rat orthologs
    findings: []
  - id: UniProt:P11798
    title: UniProt record for Camk2a (P11798)
    findings: []
  - id: GO_REF:0000116
    title: Automatic Gene Ontology annotation based on Rhea mapping
    findings: []
  - id: GO_REF:0000117
    title: Electronic Gene Ontology annotations created by ARBA machine learning
      models
    findings: []
  - id: GO_REF:0000119
    title: Automated transfer of experimentally-verified manual GO annotation 
      data to mouse-human orthologs
    findings: []
  - id: GO_REF:0000120
    title: Combined Automated Annotation using Multiple IEA Methods
    findings: []
  - id: PMID:10862698
    title: Proteomic analysis of NMDA receptor-adhesion protein signaling 
      complexes.
    findings: []
  - id: PMID:12223541
    title: 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.
    findings: []
  - id: PMID:12629219
    title: Essential function of alpha-calcium/calmodulin-dependent protein 
      kinase II in neurotransmitter release at a glutamatergic central synapse.
    findings: []
  - id: PMID:12660151
    title: Calcineurin-independent regulation of plasma membrane Ca2+ ATPase-4 
      in the vascular smooth muscle cell cycle.
    findings: []
  - id: PMID:15140879
    title: Regulation of the multifunctional Ca2+/calmodulin-dependent protein 
      kinase II by the PP2C phosphatase PPM1F in fibroblasts.
    findings: []
  - id: PMID:15994560
    title: Variable control of Ets-1 DNA binding by multiple phosphates in an 
      unstructured region.
    findings: []
  - id: PMID:16120608
    title: Multivalent interactions of calcium/calmodulin-dependent protein 
      kinase II with the postsynaptic density proteins NR2B, densin-180, and 
      alpha-actinin-2.
    findings: []
  - id: PMID:16710293
    title: NR2B tyrosine phosphorylation modulates fear learning as well as 
      amygdaloid synaptic plasticity.
    findings: []
  - id: PMID:17114649
    title: Qualitative and quantitative analyses of protein phosphorylation in 
      naive and stimulated mouse synaptosomal preparations.
    findings: []
  - id: PMID:17610578
    title: 'Alpha-synuclein involvement in hippocampal synaptic plasticity: role of
      NO, cGMP, cGK and CaMKII.'
    findings: []
  - id: PMID:17660813
    title: Kinase activity is not required for alphaCaMKII-dependent presynaptic
      plasticity at CA3-CA1 synapses.
    findings: []
  - id: PMID:18480293
    title: Phosphorylation of Homer3 by calcium/calmodulin-dependent kinase II 
      regulates a coupling state of its target molecules in Purkinje cells.
    findings: []
  - id: PMID:19455133
    title: Targeted tandem affinity purification of PSD-95 recovers core 
      postsynaptic complexes and schizophrenia susceptibility proteins.
    findings: []
  - id: PMID:20141836
    title: DAPK1 interaction with NMDA receptor NR2B subunits mediates brain 
      damage in stroke.
    findings: []
  - id: PMID:22234183
    title: CaMKII binding to GluN2B is critical during memory consolidation.
    findings: []
  - id: PMID:23051746
    title: CaMKII determines mitochondrial stress responses in heart.
    findings: []
  - id: PMID:23502535
    title: CaMKII regulates diacylglycerol lipase-α and striatal endocannabinoid
      signaling.
    findings: []
  - id: PMID:24725413
    title: Activity-dependent p25 generation regulates synaptic plasticity and 
      Aβ-induced cognitive impairment.
    findings: []
  - id: PMID:25297099
    title: The schizophrenia susceptibility gene dysbindin regulates dendritic 
      spine dynamics.
    findings: []
  - id: PMID:28130356
    title: A Novel Human CAMK2A Mutation Disrupts Dendritic Morphology and 
      Synaptic Transmission, and Causes ASD-Related Behaviors.
    findings: []
  - id: PMID:28642476
    title: Prevention of long-term memory loss after retrieval by an endogenous 
      CaMKII inhibitor.
    findings: []
  - id: PMID:28671696
    title: Spatiotemporal profile of postsynaptic interactomes integrates 
      components of complex brain disorders.
    findings: []
  - id: file:mouse/Camk2a/Camk2a-deep-research-falcon.md
    title: Falcon deep research summary for mouse Camk2a
    findings:
      - statement: CaMKIIalpha is a Ca2+/calmodulin-regulated serine/threonine
          kinase whose T286 autophosphorylation and substrate phosphorylation support
          synaptic plasticity.
      - statement: Falcon synthesis emphasizes GluN2B/NMDA receptor binding as a
          central non-catalytic scaffolding function at the postsynaptic density.
core_functions:
  - molecular_function:
      id: GO:0004683
      label: calcium/calmodulin-dependent protein kinase activity
    description: Phosphorylates serine/threonine residues on target proteins in 
      response to Ca2+/calmodulin activation. Autophosphorylation at Thr-286 
      switches kinase to constitutively active state.
    locations:
      - id: GO:0045202
        label: synapse
      - id: GO:0014069
        label: postsynaptic density
      - id: GO:0043197
        label: dendritic spine
    directly_involved_in:
      - id: GO:0006468
        label: protein phosphorylation
      - id: GO:0018105
        label: peptidyl-serine phosphorylation
      - id: GO:0046777
        label: protein autophosphorylation
    supported_by:
      - reference_id: UniProt:P11798
        supporting_text: Calcium/calmodulin-dependent protein kinase that functions
          autonomously after Ca2+/calmodulin binding and autophosphorylation.
      - reference_id: file:mouse/Camk2a/Camk2a-deep-research-falcon.md
        supporting_text: Falcon synthesis supports CaMKIIalpha as a Ca2+/calmodulin-regulated
          Ser/Thr kinase with T286 autophosphorylation and postsynaptic substrate
          phosphorylation as central activities.
  - molecular_function:
      id: GO:0035254
      label: glutamate receptor binding
    description: 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.
    locations:
      - id: GO:0098685
        label: Schaffer collateral - CA1 synapse
      - id: GO:0014069
        label: postsynaptic density
    directly_involved_in:
      - id: GO:0048168
        label: regulation of neuronal synaptic plasticity
    supported_by:
      - reference_id: PMID:22234183
        supporting_text: CaMKII binding to GluN2B is critical during memory consolidation.
      - reference_id: file:mouse/Camk2a/Camk2a-deep-research-falcon.md
        supporting_text: Falcon synthesis identifies GluN2B/NMDAR binding as a
          core CaMKIIalpha structural and scaffolding function at excitatory synapses.
  - molecular_function:
      id: GO:0005516
      label: calmodulin binding
    description: Binds Ca2+/calmodulin through the regulatory segment, relieving
      autoinhibition and enabling kinase activation and T286 trans-autophosphorylation.
    locations:
      - id: GO:0043197
        label: dendritic spine
      - id: GO:0030425
        label: dendrite
    directly_involved_in:
      - id: GO:0006468
        label: protein phosphorylation
    supported_by:
      - reference_id: UniProt:P11798
        supporting_text: Calcium/calmodulin-dependent protein kinase that functions
          autonomously after Ca2+/calmodulin binding and autophosphorylation.
      - reference_id: file:mouse/Camk2a/Camk2a-deep-research-falcon.md
        supporting_text: Falcon synthesis describes Ca2+/calmodulin binding to the
          regulatory segment as the activation mechanism for CaMKIIalpha holoenzymes.

Gene Description

Existing Annotations Review

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.

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.

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

References

Deep Research

Falcon

Research report: Mouse Camk2a (CaMKIIα; UniProt P11798)—functional annotation

0) Target verification (mandatory)

1) Key concepts and definitions (current understanding)

1.1 What CaMKIIα is

1.2 Domain architecture and holoenzyme organization

1.3 Enzymatic reaction (primary biochemical function)

2) Biochemical mechanism, regulation, and substrate specificity

2.1 Ca(^2+)/CaM activation and autonomous activity

2.2 Post-translational modifications (PTMs) emphasized in 2023–2024

3) Subcellular localization and pathway roles (synaptic signaling and plasticity)

3.1 Localization: postsynaptic density (PSD) and NMDAR anchoring

3.2 LTP pathway logic and timing (2024 advance)

4) Recent developments and latest research (prioritizing 2023–2024)

4.1 2024: Endogenous in vivo substrate discovery in adult mouse cortex (phosphoproteomics)

4.2 2023: S-nitrosylation deficit as a mechanistic explanation for age-like cognitive decline

5) Current applications and real-world implementations

5.1 Experimental tools for CaMKIIα research (expert standards, 2024)

5.2 Optogenetic control at single synapses (“local optogenetics,” 2023)

5.3 Camk2a regulatory elements for neuron-type targeting (Cre and AAV)

6) Relevant statistics and data highlights (recent studies)

7) Expert synthesis and interpretation

8) Summary table of findings

Key references (URLs and publication dates)

Citations

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