CAMK2A

The product of this gene belongs to the serine/threonine protein kinases family, and to the Ca(2+)/calmodulin-dependent protein kinases subfamily. Calcium signaling is crucial for several aspects of plasticity at glutamatergic synapses. This calcium calmodulin-dependent protein kinase is composed of four different chains: alpha, beta, gamma, and delta. The alpha chain encoded by this gene is required for hippocampal long-term potentiation (LTP) and spatial learning. In addition to its calcium-calmodulin (CaM)-dependent activity, this protein can undergo autophosphorylation, resulting in CaM-independent activity. Several transcript variants encoding distinct isoforms have been identified for this gene. [provided by RefSeq, Jun 2018]
Diseases associated with CAMK2A include Intellectual Developmental Disorder, Autosomal Dominant 53 and Intellectual Developmental Disorder, Autosomal Recessive 63. Among its related pathways are Calmodulin induced events and Signaling downstream of RAS mutants. Gene Ontology (GO) annotations related to this gene include protein homodimerization activity and protein kinase activity. An important paralog of this gene is CAMK2D.
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, neurotransmitter release and long-term potentiation (PubMed:14722083).
Member of the NMDAR signaling complex in excitatory synapses, it regulates NMDAR-dependent potentiation of the AMPAR and therefore excitatory synaptic transmission (By similarity).
Regulates dendritic spine development (PubMed:28130356).
Also regulates the migration of developing neurons (PubMed:29100089).
Phosphorylates the transcription factor FOXO3 to activate its transcriptional activity (PubMed:23805378).
Phosphorylates the transcription factor ETS1 in response to calcium signaling, thereby decreasing ETS1 affinity for DNA (By similarity).
In response to interferon-gamma (IFN-gamma) stimulation, catalyzes phosphorylation of STAT1, stimulating the JAK-STAT signaling pathway (PubMed:11972023).
In response to interferon-beta (IFN-beta) stimulation, stimulates the JAK-STAT signaling pathway (PubMed:35568036).
Acts as a negative regulator of 2-arachidonoylglycerol (2-AG)-mediated synaptic signaling via modulation of DAGLA activity (By similarity).
Activated by Ca(2+)/calmodulin.
Binding of calmodulin results in conformational change that relieves intrasteric autoinhibition and allows autophosphorylation of Thr-286 which turns the kinase in a constitutively active form and confers to the kinase a Ca(2+)-independent activity.
rat calcium/calmodulin dependent protein kinase type II chain homolog
Synapse {ECO:0000250 UniProtKB:P11275}
Postsynaptic density {ECO:0000250 UniProtKB:P11275}
Cell projection, dendritic spine {ECO:0000269 PubMed:28130356}
Cell projection, dendrite {ECO:0000269 PubMed:28130356}
Note: Postsynaptic lipid rafts {ECO:0000250 UniProtKB:P11275}
cytosol 5
nucleus{PubMed:21630459}5
Quaternary structure:
There are 4 genes encoding calcium/calmodulin-dependent protein kinase type II chains: CAMK2A, CAMK2B, CAMK2G and CAMK2D.
The corresponding proteins assemble into homo- or heteromultimeric holoenzymes composed of 12 subunits with two hexameric rings stacked one on top of the other (PubMed:14722083, 29784083).
Interacts with BAALC.
Interacts with MPDZ.
Interacts with SYN1.
Interacts with CAMK2N2.
Interacts with SYNGAP1.
Interacts with SYNPO2 (By similarity).
Interacts with SHANK3 (PubMed:28130356).
Interacts with GRIN2B (PubMed:28130356).
Interacts with CACNB2 (PubMed:28130356).
Interacts with LRRC7 (PubMed:28130356).
Interacts with GRM5 (PubMed:28130356).
Interacts with DAGLA (via C-terminal); this interaction is enhanced by autophosphorylation of CAMK2A at Thr-286 (By similarity).
Interacts with CAMK2N1; this interaction requires CAMK2A activation by Ca(2+) (By similarity).