CAMK2A/A0011

CAMK2A, also known as A0011, is the alpha subunit of the calcium/calmodulin-dependent protein kinase II (CaM kinase II).

CAMK2A, also known as A0011, is the alpha subunit of the calcium/calmodulin-dependent protein kinase II (CaM kinase II). This protein is a heteromultimeric holoenzyme composed of 8 to 12 subunits: alpha, beta, gamma or delta in a variable ratio. The two main subunits in the brain are alpha and beta; these subunits form the holoenzymes that constitute 1–2% of total brain protein in rats. It is enriched at synapses and is the main protein of the post-synaptic density region. The catalytic activity of CAMK2A is triggered in a calcium-dependent manner, following auto-phosphorylation that becomes independent of calcium. CAMK2 translocates to synapses and binds directly to the N-methyl-D-aspartate (NMDA) receptor in response to calcium ion entry through this receptor. This protein regulates alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor (AMPAR) properties and the synaptic incorporation of AMPARs in response to synaptic activity. Activity-dependent regulation of AMPAR levels in excitatory synapses is a critical mechanism for changing synaptic strength during NMDA receptor-dependent long-term potentiation (LTP). This is demonstrated by the finding that LTP in hippocampal pyramidal cells is abolished mutant alpha-isoform CAMK2A mice without the autophosphorylation site. These mice also show major defects in tests of spatial learning. Mutant mice lacking the complete subunit CAMK2A also display deficient LTP and specific impairment in spatial learning.