Calcium/calmodulin-dependent protein kinase type II subunit alpha

CAMK2A
Available structures PDB Ortholog search: PDBe RCSB List of PDB id codes 2VZ6, 3SOA, 5IG3
Identifiers
Aliases	CAMK2A, CAMKA, calcium/calmodulin dependent protein kinase II alpha, MRD53, CaMKIINalpha, MRT63, CaMKIIalpha
External IDs	OMIM: 114078; MGI: 88256; HomoloGene: 56577; GeneCards: CAMK2A; OMA:CAMK2A - orthologs
Gene location (Human) Chr. Chromosome 5 (human) Band 5q32 Start 150,219,491 bp End 150,290,093 bp
Gene location (Mouse) Chr. Chromosome 18 (mouse) Band 18 E1|18 34.41 cM Start 61,058,690 bp End 61,121,224 bp
RNA expression pattern Bgee Human Mouse (ortholog) Top expressed in amygdala prefrontal cortex right frontal lobe Region I of hippocampus proper Brodmann area 9 cingulate gyrus anterior cingulate cortex frontal pole orbitofrontal cortex Brodmann area 46 Top expressed in dentate gyrus of hippocampal formation granule cell superior frontal gyrus lateral septal nucleus olfactory tubercle muscle of thigh anterior amygdaloid area piriform cortex subiculum primary visual cortex perirhinal cortex More reference expression data BioGPS n/a
Gene ontology Molecular function transferase activity nucleotide binding protein kinase activity protein homodimerization activity kinase activity protein binding glutamate receptor binding ATP binding metal ion binding protein serine/threonine kinase activity calmodulin binding calmodulin-dependent protein kinase activity calcium-dependent protein serine/threonine kinase activity identical protein binding Cellular component endocytic vesicle membrane cytosol membrane plasma membrane synapse nucleoplasm cell junction presynaptic membrane nucleus cytoplasm mitochondrion postsynaptic density neuron projection calcium- and calmodulin-dependent protein kinase complex dendrite cell projection dendritic spine postsynaptic membrane Schaffer collateral - CA1 synapse Biological process phosphorylation interferon-gamma-mediated signaling pathway G1 phase angiotensin-activated signaling pathway positive regulation of cardiac muscle cell apoptotic process regulation of neurotransmitter secretion regulation of mitochondrial membrane permeability involved in apoptotic process MAPK cascade response to ischemia positive regulation of NF-kappaB transcription factor activity regulation of cellular response to heat regulation of neuronal synaptic plasticity protein autophosphorylation calcium ion transport positive regulation of calcium ion transport dendrite morphogenesis Wnt signaling pathway, calcium modulating pathway nervous system development peptidyl-serine phosphorylation peptidyl-threonine phosphorylation cell differentiation intracellular signal transduction protein phosphorylation G1/S transition of mitotic cell cycle dendritic spine development regulation of synaptic vesicle docking peptidyl-threonine autophosphorylation regulation of neuron migration Sources:Amigo / QuickGO
Orthologs Species Human Mouse Entrez 815 12322 Ensembl ENSG00000070808 ENSMUSG00000024617 UniProt Q9UQM7 P11798 RefSeq (mRNA) NM_171825 NM_015981 NM_001363989 NM_001363990 NM_001369025 NM_001286809 NM_009792 NM_177407 RefSeq (protein) NP_057065 NP_741960 NP_001350918 NP_001350919 NP_001355954 NP_001273738 NP_033922 NP_803126 NP_001390238 NP_001390241 Location (UCSC) Chr 5: 150.22 – 150.29 Mb Chr 18: 61.06 – 61.12 Mb PubMed search
Wikidata
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Calcium/calmodulin-dependent protein kinase type II subunit alpha (CAMKIIα), a.k.a. Ca²⁺/calmodulin-dependent protein kinase II alpha, is one subunit of CamKII, a protein kinase (i.e., an enzyme which phosphorylates proteins) that in humans is encoded by the CAMK2A gene.

Function

The product of the CAMK2A gene is an enzyme that belongs to the serine/threonine-specific protein kinase family, as well as the Ca²⁺/calmodulin-dependent protein kinase II subfamily. Ca²⁺ signaling is crucial for several aspects of synaptic plasticity at glutamatergic synapses. This enzyme 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. Two transcript variants encoding distinct isoforms have been identified for this gene. According to a 2018 study by Bruno Reversade, the recessive mutation of CAMK2A in humans cause a syndrome of severe intellectual disability with growth retardation.

Interactions

CAMK2A has been shown to interact with:

• Actinin alpha 4,
• CDK5R1, and
• DLG1.

Further reading

• Soderling TR (June 2000). "CaM-kinases: modulators of synaptic plasticity". Current Opinion in Neurobiology. 10 (3): 375–80. doi:10.1016/S0959-4388(00)00090-8. PMID 10851169. S2CID 31122499.
• Hook SS, Means AR (2001). "Ca(2+)/CaM-dependent kinases: from activation to function". Annual Review of Pharmacology and Toxicology. 41 (1): 471–505. doi:10.1146/annurev.pharmtox.41.1.471. PMID 11264466.
• Yamamoto H (March 2002). "[Molecular mechanisms of the intracellular localizations of Ca2+/calmodulin-dependent protein kinase II isoforms, and their physiological functions]". Tanpakushitsu Kakusan Koso. Protein, Nucleic Acid, Enzyme. 47 (3): 241–7. PMID 11889801.
• Countaway JL, Nairn AC, Davis RJ (January 1992). "Mechanism of desensitization of the epidermal growth factor receptor protein-tyrosine kinase". The Journal of Biological Chemistry. 267 (2): 1129–40. doi:10.1016/S0021-9258(18)48406-2. PMID 1309762.
• Wegner M, Cao Z, Rosenfeld MG (April 1992). "Calcium-regulated phosphorylation within the leucine zipper of C/EBP beta". Science. 256 (5055): 370–3. Bibcode:1992Sci...256..370W. doi:10.1126/science.256.5055.370. PMID 1314426. S2CID 34818876.
• Omary MB, Baxter GT, Chou CF, Riopel CL, Lin WY, Strulovici B (May 1992). "PKC epsilon-related kinase associates with and phosphorylates cytokeratin 8 and 18". The Journal of Cell Biology. 117 (3): 583–93. doi:10.1083/jcb.117.3.583. PMC 2289443. PMID 1374067.
• Bredt DS, Ferris CD, Snyder SH (June 1992). "Nitric oxide synthase regulatory sites. Phosphorylation by cyclic AMP-dependent protein kinase, protein kinase C, and calcium/calmodulin protein kinase; identification of flavin and calmodulin binding sites". The Journal of Biological Chemistry. 267 (16): 10976–81. doi:10.1016/S0021-9258(19)49862-1. PMID 1375933.
• Tokui T, Yamauchi T, Yano T, Nishi Y, Kusagawa M, Yatani R, Inagaki M (June 1990). "Ca2(+)-calmodulin-dependent protein kinase II phosphorylates various types of non-epithelial intermediate filament proteins". Biochemical and Biophysical Research Communications. 169 (3): 896–904. doi:10.1016/0006-291X(90)91977-Z. PMID 2114109.
• Inagaki M, Gonda Y, Nishizawa K, Kitamura S, Sato C, Ando S, et al. (March 1990). "Phosphorylation sites linked to glial filament disassembly in vitro locate in a non-alpha-helical head domain". The Journal of Biological Chemistry. 265 (8): 4722–9. doi:10.1016/S0021-9258(19)39622-X. PMID 2155236.
• Ohta Y, Ohba T, Miyamoto E (July 1990). "Ca2+/calmodulin-dependent protein kinase II: localization in the interphase nucleus and the mitotic apparatus of mammalian cells". Proceedings of the National Academy of Sciences of the United States of America. 87 (14): 5341–5. Bibcode:1990PNAS...87.5341O. doi:10.1073/pnas.87.14.5341. PMC 54319. PMID 2164678.
• Lee RH, Brown BM, Lolley RN (September 1990). "Protein kinase A phosphorylates retinal phosducin on serine 73 in situ". The Journal of Biological Chemistry. 265 (26): 15860–6. doi:10.1016/S0021-9258(18)55478-8. PMID 2394752.
• Ku NO, Omary MB (October 1994). "Identification of the major physiologic phosphorylation site of human keratin 18: potential kinases and a role in filament reorganization". The Journal of Cell Biology. 127 (1): 161–71. doi:10.1083/jcb.127.1.161. PMC 2120194. PMID 7523419.
• Drewes G, Trinczek B, Illenberger S, Biernat J, Schmitt-Ulms G, Meyer HE, et al. (March 1995). "Microtubule-associated protein/microtubule affinity-regulating kinase (p110mark). A novel protein kinase that regulates tau-microtubule interactions and dynamic instability by phosphorylation at the Alzheimer-specific site serine 262". The Journal of Biological Chemistry. 270 (13): 7679–88. doi:10.1074/jbc.270.13.7679. PMID 7706316. S2CID 2039456.
• Tsujimura K, Tanaka J, Ando S, Matsuoka Y, Kusubata M, Sugiura H, et al. (August 1994). "Identification of phosphorylation sites on glial fibrillary acidic protein for cdc2 kinase and Ca(2+)-calmodulin-dependent protein kinase II". Journal of Biochemistry. 116 (2): 426–34. doi:10.1093/oxfordjournals.jbchem.a124542. PMID 7822264.
• Toyofuku T, Curotto Kurzydlowski K, Narayanan N, MacLennan DH (October 1994). "Identification of Ser38 as the site in cardiac sarcoplasmic reticulum Ca(2+)-ATPase that is phosphorylated by Ca2+/calmodulin-dependent protein kinase". The Journal of Biological Chemistry. 269 (42): 26492–6. doi:10.1016/S0021-9258(18)47221-3. PMID 7929371.
• Rivera VM, Miranti CK, Misra RP, Ginty DD, Chen RH, Blenis J, Greenberg ME (October 1993). "A growth factor-induced kinase phosphorylates the serum response factor at a site that regulates its DNA-binding activity". Molecular and Cellular Biology. 13 (10): 6260–73. doi:10.1128/mcb.13.10.6260. PMC 364685. PMID 8413226.
• Omkumar RV, Kiely MJ, Rosenstein AJ, Min KT, Kennedy MB (December 1996). "Identification of a phosphorylation site for calcium/calmodulindependent protein kinase II in the NR2B subunit of the N-methyl-D-aspartate receptor". The Journal of Biological Chemistry. 271 (49): 31670–8. doi:10.1074/jbc.271.49.31670. PMID 8940188. S2CID 8332020.
• Rotenberg A, Mayford M, Hawkins RD, Kandel ER, Muller RU (December 1996). "Mice expressing activated CaMKII lack low frequency LTP and do not form stable place cells in the CA1 region of the hippocampus". Cell. 87 (7): 1351–61. doi:10.1016/S0092-8674(00)81829-2. PMID 8980240. S2CID 16704390.
• Paudel HK (January 1997). "The regulatory Ser262 of microtubule-associated protein tau is phosphorylated by phosphorylase kinase". The Journal of Biological Chemistry. 272 (3): 1777–85. doi:10.1016/S0021-9258(19)67481-8. PMID 8999860.

External links

• Human CAMK2A genome location and CAMK2A gene details page in the UCSC Genome Browser.