CAMK2A (calcium/calmodulin dependent protein kinase II alpha)

Gene

• Entrez ID: 815
• Gene name: Calcium/calmodulin dependent protein kinase II alpha
• Gene symbol: CAMK2A
• Synonyms: CAMKA, CaMKIINalpha, CaMKIIalpha, MRD53, MRT63
• Chromosome: 5
• Chromosome location: 5q32
• Summary: 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]

SNPs

SNP ID	Visualize variation	Clinical significance	Consequence
rs113331868	C>A,T	Pathogenic	Splice donor variant
rs864309606	G>A	Uncertain-significance, pathogenic	Coding sequence variant, missense variant
rs926027867	G>A,T	Pathogenic	Coding sequence variant, missense variant
rs1287121256	C>G,T	Pathogenic	Missense variant, coding sequence variant, synonymous variant
rs1554119274	G>A	Pathogenic	Coding sequence variant, missense variant
rs1554121872	T>G	Pathogenic	Coding sequence variant, missense variant
rs1554121875	T>C	Pathogenic	Coding sequence variant, missense variant
rs1554121878	C>T	Pathogenic	Splice acceptor variant
rs1554122123	->A	Likely-pathogenic	Splice donor variant
rs1554122129	T>A	Pathogenic	Coding sequence variant, missense variant
rs1554122526	A>G	Pathogenic	Coding sequence variant, missense variant
rs1554123982	C>-	Likely-pathogenic	Coding sequence variant, splice acceptor variant
rs1562164380	C>T	Likely-pathogenic	Stop gained, coding sequence variant
rs1580966945	C>T	Likely-pathogenic	Missense variant, coding sequence variant

miRNA

miRTarBase ID	miRNA	Experiments	Reference
MIRT457373	hsa-miR-4665-5p	PAR-CLIP	23592263
MIRT457374	hsa-miR-1275	PAR-CLIP	23592263
MIRT457375	hsa-miR-4472	PAR-CLIP	23592263
MIRT457376	hsa-miR-4447	PAR-CLIP	23592263
MIRT457377	hsa-miR-92a-2-5p	PAR-CLIP	23592263
MIRT457378	hsa-miR-5010-5p	PAR-CLIP	23592263
MIRT457379	hsa-miR-7111-5p	PAR-CLIP	23592263
MIRT457380	hsa-miR-4525	PAR-CLIP	23592263
MIRT457381	hsa-miR-6870-5p	PAR-CLIP	23592263
MIRT457382	hsa-miR-5698	PAR-CLIP	23592263
MIRT457383	hsa-miR-4723-5p	PAR-CLIP	23592263
MIRT457384	hsa-miR-625-5p	PAR-CLIP	23592263
MIRT457385	hsa-miR-486-3p	PAR-CLIP	23592263
MIRT457386	hsa-miR-6825-5p	PAR-CLIP	23592263
MIRT457387	hsa-miR-6721-5p	PAR-CLIP	23592263
MIRT457388	hsa-miR-6883-5p	PAR-CLIP	23592263
MIRT457389	hsa-miR-6785-5p	PAR-CLIP	23592263
MIRT457390	hsa-miR-4728-5p	PAR-CLIP	23592263
MIRT457391	hsa-miR-149-3p	PAR-CLIP	23592263
MIRT457392	hsa-miR-4736	PAR-CLIP	23592263
MIRT457393	hsa-miR-505-5p	PAR-CLIP	23592263
MIRT457394	hsa-miR-3665	PAR-CLIP	23592263
MIRT457395	hsa-miR-8082	PAR-CLIP	23592263
MIRT457396	hsa-miR-4534	PAR-CLIP	23592263
MIRT457397	hsa-miR-6743-5p	PAR-CLIP	23592263
MIRT457398	hsa-miR-4688	PAR-CLIP	23592263
MIRT529404	hsa-miR-1251-3p	PAR-CLIP	22012620
MIRT529405	hsa-miR-520f-3p	PAR-CLIP	22012620
MIRT529406	hsa-miR-302c-3p	PAR-CLIP	22012620

Gene ontology (GO)

GO ID	Ontology	Definition	Evidence	Reference
GO:0000082	Process	G1/S transition of mitotic cell cycle	ISS
GO:0002931	Process	Response to ischemia	ISS
GO:0004674	Function	Protein serine/threonine kinase activity	IDA	28130356
GO:0004674	Function	Protein serine/threonine kinase activity	ISS
GO:0004683	Function	Calmodulin-dependent protein kinase activity	IBA	21873635
GO:0004683	Function	Calmodulin-dependent protein kinase activity	IMP	18305109
GO:0005515	Function	Protein binding	IPI	17052756, 18305109, 19453375, 20668654, 22939624, 25852190, 27173435, 28130356, 29426014, 31980649, 32296183, 32814053
GO:0005516	Function	Calmodulin binding	IBA	21873635
GO:0005516	Function	Calmodulin binding	IPI	20668654
GO:0005524	Function	ATP binding	IEA
GO:0005634	Component	Nucleus	HDA	21630459
GO:0005654	Component	Nucleoplasm	TAS
GO:0005737	Component	Cytoplasm	IBA	21873635
GO:0005739	Component	Mitochondrion	ISS
GO:0005829	Component	Cytosol	TAS
GO:0005954	Component	Calcium- and calmodulin-dependent protein kinase complex	IDA	20668654, 28130356
GO:0006468	Process	Protein phosphorylation	IDA	17052756
GO:0006468	Process	Protein phosphorylation	IMP	18305109
GO:0006816	Process	Calcium ion transport	ISS
GO:0007223	Process	Wnt signaling pathway, calcium modulating pathway	TAS
GO:0009931	Function	Calcium-dependent protein serine/threonine kinase activity	IMP	18305109
GO:0010666	Process	Positive regulation of cardiac muscle cell apoptotic process	ISS
GO:0014069	Component	Postsynaptic density	IEA
GO:0016301	Function	Kinase activity	IDA	17052756
GO:0018105	Process	Peptidyl-serine phosphorylation	ISS
GO:0030666	Component	Endocytic vesicle membrane	TAS
GO:0035254	Function	Glutamate receptor binding	ISS
GO:0038166	Process	Angiotensin-activated signaling pathway	IDA	20584908
GO:0042802	Function	Identical protein binding	IPI	20668654, 21884935
GO:0042803	Function	Protein homodimerization activity	IPI	20668654
GO:0043005	Component	Neuron projection	IBA	21873635
GO:0043197	Component	Dendritic spine	IDA	28130356
GO:0046777	Process	Protein autophosphorylation	ISS
GO:0046872	Function	Metal ion binding	IEA
GO:0046928	Process	Regulation of neurotransmitter secretion	ISS
GO:0048168	Process	Regulation of neuronal synaptic plasticity	ISS
GO:0051092	Process	Positive regulation of NF-kappaB transcription factor activity	IMP	17052756
GO:0051346	Process	Negative regulation of hydrolase activity	ISS
GO:0051928	Process	Positive regulation of calcium ion transport	ISS
GO:0060333	Process	Interferon-gamma-mediated signaling pathway	TAS
GO:0060996	Process	Dendritic spine development	IMP	28130356
GO:1900034	Process	Regulation of cellular response to heat	TAS
GO:1902108	Process	Regulation of mitochondrial membrane permeability involved in apoptotic process	ISS
GO:1990443	Process	Peptidyl-threonine autophosphorylation	IMP	28130356
GO:2000124	Process	Regulation of endocannabinoid signaling pathway	ISS
GO:2001222	Process	Regulation of neuron migration	IMP	29100089

Other IDs

• MIM: 114078
• HGNC: 1460
• e!Ensembl: ENSG00000070808

Protein

• UniProt ID: Q9UQM7
• Protein name: Calcium/calmodulin-dependent protein kinase type II subunit alpha (CaM kinase II subunit alpha) (CaMK-II subunit alpha) (EC 2.7.11.17)
• Protein function: Calcium/calmodulin-dependent protein kinase that functions autonomously after Ca(2+)/calmodulin-binding and autophosphorylation, and is involved in synaptic plasticity, neurotransmitter release and long-term potentiation. 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). Acts as a negative regulator of 2-arachidonoylglycerol (2-AG)-mediated synaptic signaling via modulation of DAGLA activity (By similarity).
• PDB: 2VZ6, 3SOA, 5IG3, 6OF8, 6VZK, 6W4O, 6W4P, 6X5G, 6X5Q, 6X8V, 6XBP, 6XBX, 6XDL, 6XDU, 6XF0, 6XOE, 7KL0, 7KL1, 7KL2, 7KL4
• Family and domains:

  Pfam

  Accession	ID	Position in sequence	Description	Type
  PF00069	Pkinase	13 → 271	Protein kinase domain	Domain
  PF08332	CaMKII_AD	346 → 473	Calcium/calmodulin dependent protein kinase II association domain	Domain

• Sequence:

  MATITCTRFTEEYQLFEELGKGAFSVVRRCVKVLAGQEYAAKIINTKKLSARDHQKLERE
  ARICRLLKHPNIVRLHDSISEEGHHYLIFDLVTGGELFEDIVAREYYSEADASHCIQQIL
  EAVLHCHQMGVVHRDLKPENLLLASKLKGAAVKLADFGLAIEVEGEQQAWFGFAGTPGYL
  SPEVLRKDPYGKPVDLWACGVILYILLVGYPPFWDEDQHRLYQQIKAGAYDFPSPEWDTV
  TPEAKDLINKMLTINPSKRITAAEALKHPWISHRSTVASCMHRQETVDCLKKFNARRKLK
  GAILTTMLATRNFSGGKSGGNKKSDGVKESSESTNTTIEDEDTKVRKQEIIKVTEQLIEA
  ISNGDFESYTKMCDPGMTAFEPEALGNLVEGLDFHRFYFENLWSRNSKPVHTTILNPHIH
  LMGDESACIAYIRITQYLDAGGIPRTAQSEETRVWHRRDGKWQIVHFHRSGAPSVLPH

• Sequence length: 478