Selected-GenAtlas references SOURCE GeneCards NCBI Gene Swiss-Prot Ensembl
HGNC UniGene Nucleotide OMIM UCSC
Home Page
Symbol CAMK2A contributors: mct/pgu - updated : 01-02-2017
HGNC name calcium/calmodulin-dependent protein kinase II alpha
HGNC id 1460
Corresponding disease
MRD53 Mental retardation, autosomal dominant 53
MRT63 mental retardation, autosomal recessive 63
Location 5q32      Physical location : 149.599.053 - 149.669.403
Synonym name
  • calcium/calmodulin-dependent protein kinase (CaM kinase) II alpha
  • CaM-kinase II alpha chain
  • calcium/calmodulin-dependent protein kinase II alpha-B subunit
  • CaM kinase II alpha subunit
  • calcium/calmodulin-dependent protein kinase type II alpha chain
  • calmodulin kinase II-related anchoring protein
  • Synonym symbol(s) KIAA0968, CAMKA, KCCA, CAMKII, CaMKIINalpha, Alphakap
    TYPE functioning gene
    STRUCTURE 70.35 kb     19 Exon(s)
    10 Kb 5' upstream gene genomic sequence study
    regulatory sequence Promoter
    Binding site   silencer   HRE
    text structure
  • promoter displayed high activity in the neuronal cell lines, while the activity was low in non-neuronal cell lines
  • two RA response elements located between +11 and +136 and -1911 to -593 and a potent silencer at position -179 to -244
  • MAPPING cloned Y linked N status confirmed
    TRANSCRIPTS type messenger
    identificationnb exonstypebpproduct
    ProteinkDaAAspecific expressionYearPubmed
    18 splicing 4885 54 478 - 2008 18305109
  • variant 2 - alpha
  • lacking an in-frame segment of the coding region compared to variant 1
  • 19 splicing 4918 55.2 489 - 2008 18305109
  • variant 1 - alpha B
  • having a 33-bp insertion relative to alpha
    Type restricted
       expressed in (based on citations)
    SystemOrgan level 1Organ level 2Organ level 3Organ level 4LevelPubmedSpeciesStageRna symbol
    Digestivemouthtongue  moderately
    Nervousbrain   specific Homo sapiens
     brainlimbic systemhippocampusdentate gyrushighly Mus musculus
    Reproductivemale systemtestis    Homo sapiens
    SystemTissueTissue level 1Tissue level 2LevelPubmedSpeciesStageRna symbol
    cell lineage
    cell lines
    fluid/secretion blood
    at STAGE
    physiological period fetal
    Text brain
  • a tyrosine kinase catalytic domain
  • conjugated PhosphoP
    mono polymer heteromer , tetramer
    interspecies ortholog to C.elegans unc-43
    ortholog to rattus Camk2a (99.8pc)
    ortholog to murine Camk2a (99.8pc)
    homolog to Drosophila CaMKII (71pc)
  • protein kinase superfamily
  • CAMK Ser/Thr protein kinase family
  • CaMK subfamily
  • CAMK subfamily
  • CATEGORY enzyme , regulatory
    SUBCELLULAR LOCALIZATION     plasma membrane,junction
  • postsynaptic density
  • colocalizes with MPDZ in the acrosomal region of epididymal spermatozoa where the kinase selectively binds to a region encompassing PDZ domains 10-11 of MPDZ
  • translocates to excitatory synapses following strong glutamatergic stimuli that induce NMDA-receptor (NMDAR)-dependent long-term potentiation in CA1 hippocampal neurons
  • basic FUNCTION
  • phosphorylation of numerous synaptic substrates including ion channels, other signaling molecules and scaffolding proteins
  • involved in synaptic plasticity and memory formation in the hippocampus
  • required with Ca2+ and calmodulin for an essential step in initiation of centrosome duplication
  • may function in long-term potentiation and neurotransmitter release
  • may regulate NMDAR-dependent potentiation of the AMPAR and synaptic plasticity
  • plays a critical role in the growth of osteosarcoma
  • regulates CHRM4 efficacy and controls the acetylcholine-dopamine balance in the basal ganglia and also the dynamics of movement
  • its activity is necessary for spine enlargement during long-term potentiation, and it is a critical control point in the determination of spine size
  • CAMK2A-dependent processes control synaptic strength and spine size
  • has a central role in regulating neuronal excitability
  • crucial effector of PKD2 Ca++ that both promotes morphogenesis of the pronephric kidney and stabilizes primary cloacal cilia
  • CAMK2A, CAMK2B act in concert, but with distinct functions, to regulate hippocampal synaptic plasticity and learning
  • central role in the neurotoxicology of Cadmium (Cd), suggesting that manipulation of intracellular Ca(2+) level or CAMK2A activity may be exploited for prevention of Cd-induced neurodegenerative disorders
  • role in maintaining the stability of nicotinic acetylcholine receptors
  • importance of tightly controlled autophosphorylation of CAMK2A for normal neuronal function, suggesting that disruption of this event can impair synaptic plasticity and learning, resulting in neurodevelopmental defects
  • kinase activity of CAMK2A plays a crucial role in the proteasomal degradation of NCOR2
  • is an important decoder of Ca(2+) signals and mediator of synaptic plasticity
  • could decode compartmental dendritic Ca(2+) transients to support remodeling of local synapses
  • CAMK2A activity is a central mechanism for mitochondrial Ca2+ entry
  • is a modulator of mitochondrial Ca2+ homeostasis and a crucial component of a final pathway in heart disease due to ischemia and neurohumoral toxicity
  • acts as a key regulator of osteoblast differentiation
  • plays a key role in N-methyl-D-aspartate (NMDA) receptor-dependent long-term synaptic plasticity
  • is an important nodal point in both acute and chronic modulation of ion channels in both heart and brain
  • CAMK2A, CAMK2B are essential for various forms of synaptic plasticity
  • dual role of CAMK2A as a component of cell-autonomous clockwork and as a synchronizer integrating circadian behavioral activities
  • elevated CAMK2A content promotes a slow-to-fast type fibre shift in regenerating muscle but is not sufficient to stimulate mitochondrial biogenesis in the absence of an endurance stimulus
  • is a regulator of the barrier function of Tight junctions (TJs)
  • CAMK2A controls likely the initiation of the memory reconsolidation process through regulation of the proteasome
  • in addition to MYLK3 contributes to phosphorylation of regulatory light chain in cardiomyocytes
  • plays a previously unappreciated role in autism spectrum disorder(ASD)-related synaptic and behavioral phenotypes
    PHYSIOLOGICAL PROCESS nervous system
    signaling neurotransmission
    neuronal transmission
    a component
  • involved in CAMK2 complex which is composed of four different chains: alpha, beta, gamma, and delta
  • involved in different isoforms assemble into homo- or heteromultimeric holoenzymes composed of 8 to 12 subunits
  • member of the NMDAR signaling complex in excitatory synapses
  • CAMK2A forms stable complexes with voltage-gated calcium channel CACNB1 or CACNB2
  • CAMK2A/NMDAR complex having potentially switch-like properties that are important in the maintenance of synaptic strength
    small molecule nucleotide,
  • ATP
  • protein
  • calmodulin
  • MPDZ
  • interacts with GJD2 (phosphorylate GJD2 in a way similar to phosphorylation of glutamate receptors)
  • directly interacts with CAMK2N1 that effectively inhibits its activity
  • regulating F-actin, which determines the postsynaptic protein binding capacity and thus may act as a synaptic tag that consolidates long-term potentiation
  • binds directly and selectively to one of five mAChR subtypes, CHRM4, at its C-terminal regions of second intracellular loops
  • CAMK2A is crucial for the regulation between NOTCH1 and WNT5A signaling
  • WNT5A inhibited the physical association between RBPJ and NCOR2 suggesting that WNT5A induced CAMK2A activation plays a critical role in the endogenous RBPJ-NCOR2 binding
  • CAMK2A down-regulated the protein stability of NCOR2 through proteasomal degradation
  • SP7 is a novel target of CAMK2A and the activity of Osterix can be modulated by a novel mechanism involving CAMK2A during osteoblast differentiation
  • directly associates with and targets CAMK2A in pancreatic islets
  • OGT-modification of CAMK2A is a novel signalling event in pathways that may contribute critically to cardiac and neuronal pathophysiology in diabetes and other diseases
  • SPTBN4–targeted CAMK2A directly phosphorylates the inwardly-rectifying potassium channel, KCNJ11
  • PLAA is located in caveolae, where it interacts with PDIA3 and CAV1 to initiate rapid signaling via CAMK2A, CAMK2B
  • is an AHCYL1-interacting molecule in the central nervous system (binds to and suppresses CAMK2A kinase activity by inhibiting the binding of calmodulin to CAMK2A)
  • CAMK2A-dependent TNNI3 phosphorylation is involved in frequency-dependent myofilament Ca(2+) desensitization (FDMCD) and the consequent frequency-dependent acceleration of relaxation (FDAR) and CAMK2A inhibition removes this mechanism and thus induces diastolic dysfunction
  • cell & other
    Other autophosphorylation of thr286 allows the switch from a calmodulin-dependent to a calmodulin-independent state
    developmentally regulated
    corresponding disease(s) MRD53 , MRT63
    Other morbid association(s)
    TypeGene ModificationChromosome rearrangementProtein expressionProtein Function
    tumoral     --low  
    in osteosarcoma cell lines and in primary osteosarcoma tissue
    constitutional     --over  
    in patients with heart failure, and elevated CAMK2A expression and activity have been implicated in the transition to heart failure
    constitutional     --low  
    induced excess TJ formation in part by the activation of AMP-activated protein kinase (AMPK) and subsequent phosphorylation of CLDN1, essential for the prevention of chronic inflammatory diseases
    Variant & Polymorphism
    Candidate gene
    Therapy target
    CAMK2A inhibition could be an attractive therapeutic target to combat conventional high-grade osteosarcoma in children
    inhibition of CAMK2A-ERK interaction offers a novel therapeutic approach to limit cardiac hypertrophy
  • required (in mice) for hippocampal long-term potentiation and spatial learning
  • knockout mice