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FLASH GENE
Symbol CAMK2A contributors: mct/pgu - updated : 21-06-2012
HGNC name calcium/calmodulin-dependent protein kinase II alpha
HGNC id 1460
Location 5q33.1      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
    EC.number 2.7.11.17
    DNA
    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
    Physical map
    KIAA1985 LOC255187 5q33.1 hypothetical LOC255187 KIAA0843 FLJ36748 5q33.1 hypothetical protein FLJ36748 GRPEL2 5q33.1 GrpE-like 2, mitochondrial (E. coli) MGC3265 5q33.1 hypothetical protein MGC3265 IL17B 5q32-34 interleukin 17B CSNK1A1 13q13 casein kinase 1, alpha 1 LOC389337 5 similar to hypothetical protein 4933429F08 PERC 5q33.1 similar to hypothetical protein 4933429F08 PDE6A 5q31.3 phosphodiesterase 6A, cGMP-specific, rod, alpha SLC26A2 5q31.3 solute carrier family 26 (sulfate transporter), member 2 TIGD6 5q32 tigger transposable element derived 6 RPS20P4 5q33-qter ribosomal protein S20 pseudogene 4 CSF1R 5q31.3 colony stimulating factor 1 receptor, formerly McDonough feline sarcoma viral (v-fms) oncogene homolog RPL7P 5q33.3 ribosomal protein L7 pseudogene PDGFRB 5q31.3 platelet-derived growth factor receptor, beta polypeptide CDX1 5q31.3 caudal type homeo box transcription factor 1 SLC6A7 5q31-q32 solute carrier family 6 (neurotransmitter transporter, L-proline), member 7 CAMK2A 5q33.2 calcium/calmodulin-dependent protein kinase (CaM kinase) II alpha LOC340075 5q33.1 similar to RIKEN cDNA 9330196J05 TCOF1 5q32-q33.1 Treacher Collins-Franceschetti syndrome 1 CD74 5q31.3 CD74 antigen (invariant polypeptide of major histocompatibility complex, class II antigen-associated) RPS14 5q32 ribosomal protein S14 NDST1 5q31.3-q32 N-deacetylase/N-sulfotransferase (heparan glucosaminyl) 1 SYNPO 5q33.1 synaptopodin MYOZ3 5q33.1 myozenin 3 FLJ10290 5q33.1 hypothetical protein FLJ10290 DCTN4 5q31-q32 dynactin 4 (p62) NID67 5q33.1 putative small membrane protein NID67 LRG47 5q33.1 LRG-47-like protein ZNF300 21 zinc finger protein 300 GPX3 5q23 glutathione peroxidase 3 (plasma) TNIP1 5q32-q33.1 TNFAIP3 interacting protein 1 ANXA6 5q32 annexin A6 DKFZP434C171 5q33.1 DKFZP434C171 protein GM2A 5q32 GM2 ganglioside activator protein SLC36A3 5q33.1 solute carrier family 36 (proton/amino acid symporter), member 3 SLC36A2 5q33.1 solute carrier family 36 (proton/amino acid symporter), member 2 LOC391840 5 similar to Thyroid hormone receptor-associated protein complex 240 kDa component (Trap240) (Activator-recruited cofactor 250 kDa component) (ARC250) LOC391841 5 similar to hypothetical protein DKFZp761H0421 SLC36A1 5q33.1 solute carrier family 36 (proton/amino acid symporter), member 1
    RNA
    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
    		•
    EXPRESSION
    Type restricted
       expressed in (based on citations)
    organ(s)
    SystemOrgan level 1Organ level 2Organ level 3Organ level 4LevelPubmedSpeciesStageRna symbol
    Cardiovascularheart    
    Digestivemouthtongue  moderately
    Nervousbrain   specific Homo sapiens
    Reproductivemale systemtestis    Homo sapiens
    tissue
    SystemTissueTissue level 1Tissue level 2LevelPubmedSpeciesStageRna symbol
    Muscularstriatumskeletal  
    Nervouscentral   
    cell lineage
    cell lines
    fluid/secretion blood
    at STAGE
    physiological period fetal
    Text brain
    PROTEIN
    PHYSICAL PROPERTIES
    STRUCTURE
    motifs/domains
  • a tyrosine kinase catalytic domain
    • conjugated PhosphoP
    mono polymer heteromer , tetramer
    HOMOLOGY
    interspecies ortholog to C.elegans unc-43
    ortholog to rattus Camk2a (99.8pc)
    ortholog to murine Camk2a (99.8pc)
    homolog to Drosophila CaMKII (71pc)
    Homologene
    FAMILY
  • protein kinase superfamily
  • CAMK Ser/Thr protein kinase family
  • CaMK subfamily
  • CAMK subfamily
    • CATEGORY enzyme , regulatory
    SUBCELLULAR LOCALIZATION     plasma membrane,junction
        intracellular
    intracellular,cytoplasm,cytosolic,vesicle
    intracellular,nucleus,nucleoplasm
    text
  • 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
  • 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
    • CELLULAR PROCESS
    PHYSIOLOGICAL PROCESS nervous system
    PATHWAY
    metabolism
    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
    • INTERACTION
    DNA
    RNA
    small molecule nucleotide,
  • ATP
    • protein
  • calmodulin
  • SYNGAP1
  • 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
    • cell & other
    REGULATION
    Other autophosphorylation of thr286 allows the switch from a calmodulin-dependent to a calmodulin-independent state
    developmentally regulated
    ASSOCIATED DISORDERS
    corresponding disease(s)
    Other morbid association(s)
    TypeGene ModificationChromosome rearrangementProtein expressionProtein Function
    tumoral     --low  
    in osteosarcoma cell lines and in primary osteosarcoma tissue
    Susceptibility
    Variant & Polymorphism
    Candidate gene
    Marker
    Therapy target CAMK2A inhibition could be an attractive therapeutic target to combat conventional high-grade osteosarcoma in children
    SystemTypeDisorderPubmed
    cancer  
    CAMK2A inhibition could be an attractive therapeutic target to combat conventional high-grade osteosarcoma in children
    ANIMAL & CELL MODELS
  • required (in mice) for hippocampal long-term potentiation and spatial learning
  • knockout mice