From Wikipedia, the free encyclopedia
Protein-coding gene in the species Homo sapiens
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 .
[5]
[6]
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.[
citation needed ] 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.
[7] 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 .
[8]
Interactions
CAMK2A has been shown to
interact with:
References
^
a
b
c
GRCh38: Ensembl release 89: ENSG00000070808 –
Ensembl , May 2017
^
a
b
c
GRCm38: Ensembl release 89: ENSMUSG00000024617 –
Ensembl , May 2017
^
"Human PubMed Reference:" . National Center for Biotechnology Information, U.S. National Library of Medicine .
^
"Mouse PubMed Reference:" . National Center for Biotechnology Information, U.S. National Library of Medicine .
^ Nagase T, Ishikawa K, Suyama M, Kikuno R, Hirosawa M, Miyajima N, et al. (February 1999).
"Prediction of the coding sequences of unidentified human genes. XIII. The complete sequences of 100 new cDNA clones from brain which code for large proteins in vitro" . DNA Research . 6 (1): 63–70.
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^ Lin CR, Kapiloff MS, Durgerian S, Tatemoto K, Russo AF, Hanson P, et al. (August 1987).
"Molecular cloning of a brain-specific calcium/calmodulin-dependent protein kinase" . Proceedings of the National Academy of Sciences of the United States of America . 84 (16): 5962–6.
Bibcode :
1987PNAS...84.5962L .
doi :
10.1073/pnas.84.16.5962 .
PMC
298983 .
PMID
3475713 .
^
"Entrez Gene: CAMK2A calcium/calmodulin-dependent protein kinase (CaM kinase) II alpha" .
^ Chia PH, Zhong FL, Niwa S, Bonnard C, Utami KH, Zeng R, et al. (May 2018).
"A homozygous loss-of-function CAMK2A mutation causes growth delay, frequent seizures and severe intellectual disability" . eLife . 7 .
doi :
10.7554/eLife.32451 .
PMC
5963920 .
PMID
29784083 .
^ Walikonis RS, Oguni A, Khorosheva EM, Jeng CJ, Asuncion FJ,
Kennedy MB (January 2001).
"Densin-180 forms a ternary complex with the (alpha)-subunit of Ca2+/calmodulin-dependent protein kinase II and (alpha)-actinin" . The Journal of Neuroscience . 21 (2): 423–33.
doi :
10.1523/JNEUROSCI.21-02-00423.2001 .
PMC
6763799 .
PMID
11160423 .
^ Dhavan R, Greer PL, Morabito MA, Orlando LR, Tsai LH (September 2002).
"The cyclin-dependent kinase 5 activators p35 and p39 interact with the alpha-subunit of Ca2+/calmodulin-dependent protein kinase II and alpha-actinin-1 in a calcium-dependent manner" . The Journal of Neuroscience . 22 (18): 7879–91.
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PMC
6758084 .
PMID
12223541 .
^ Gardoni F, Mauceri D, Fiorentini C, Bellone C, Missale C, Cattabeni F, Di Luca M (November 2003).
"CaMKII-dependent phosphorylation regulates SAP97/NR2A interaction" . The Journal of Biological Chemistry . 278 (45): 44745–52.
doi :
10.1074/jbc.M303576200 .
PMID
12933808 .
S2CID
19885326 .
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
Activity Regulation Classification Kinetics Types