KCC2A_MOUSE
ID KCC2A_MOUSE Reviewed; 478 AA.
AC P11798; Q61284; Q6ZWN4;
DT 01-OCT-1989, integrated into UniProtKB/Swiss-Prot.
DT 23-JAN-2007, sequence version 2.
DT 03-AUG-2022, entry version 216.
DE RecName: Full=Calcium/calmodulin-dependent protein kinase type II subunit alpha;
DE Short=CaM kinase II subunit alpha;
DE Short=CaMK-II subunit alpha;
DE EC=2.7.11.17 {ECO:0000269|PubMed:23502535};
GN Name=Camk2a;
OS Mus musculus (Mouse).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Mus; Mus.
OX NCBI_TaxID=10090;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC STRAIN=ICR; TISSUE=Brain;
RX PubMed=2543961; DOI=10.1093/nar/17.10.3992;
RA Hanley R.M., Payne M.E., Cruzalegui F., Christenson M.A., Means A.R.;
RT "Sequence of the cDNA for the alpha subunit of calmodulin kinase II from
RT mouse brain.";
RL Nucleic Acids Res. 17:3992-3992(1989).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM ALPHA KAP), SUBCELLULAR LOCATION
RP (ISOFORM ALPHA KAP), AND TISSUE SPECIFICITY.
RC STRAIN=BALB/cJ; TISSUE=Skeletal muscle;
RX PubMed=8524307; DOI=10.1128/mcb.16.1.29;
RA Bayer K.-U., Loehler J., Harbers K.;
RT "An alternative, nonkinase product of the brain-specifically expressed
RT Ca2+/calmodulin-dependent kinase II alpha isoform gene in skeletal
RT muscle.";
RL Mol. Cell. Biol. 16:29-36(1996).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=C57BL/6J; TISSUE=Hippocampus;
RX PubMed=16141072; DOI=10.1126/science.1112014;
RA Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N.,
RA Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K.,
RA Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J.,
RA Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R.,
RA Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T.,
RA Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A.,
RA Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B.,
RA Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M.,
RA Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S.,
RA Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E.,
RA Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D.,
RA Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M.,
RA Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H.,
RA Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V.,
RA Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S.,
RA Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H.,
RA Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N.,
RA Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F.,
RA Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G.,
RA Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z.,
RA Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C.,
RA Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y.,
RA Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S.,
RA Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K.,
RA Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R.,
RA van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H.,
RA Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M.,
RA Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C.,
RA Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S.,
RA Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K.,
RA Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M.,
RA Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C.,
RA Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A.,
RA Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y.;
RT "The transcriptional landscape of the mammalian genome.";
RL Science 309:1559-1563(2005).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Eye;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [5]
RP PROTEIN SEQUENCE OF 9-21; 33-42; 135-146; 260-267; 301-311; 329-344;
RP 353-371; 397-405; 434-445 AND 470-478, AND IDENTIFICATION BY MASS
RP SPECTROMETRY.
RC STRAIN=OF1; TISSUE=Hippocampus;
RA Lubec G., Sunyer B., Chen W.-Q.;
RL Submitted (JAN-2009) to UniProtKB.
RN [6]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Brain;
RX PubMed=16452087; DOI=10.1074/mcp.t500041-mcp200;
RA Trinidad J.C., Specht C.G., Thalhammer A., Schoepfer R., Burlingame A.L.;
RT "Comprehensive identification of phosphorylation sites in postsynaptic
RT density preparations.";
RL Mol. Cell. Proteomics 5:914-922(2006).
RN [7]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT TYR-13, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Brain;
RX PubMed=18034455; DOI=10.1021/pr0701254;
RA Ballif B.A., Carey G.R., Sunyaev S.R., Gygi S.P.;
RT "Large-scale identification and evolution indexing of tyrosine
RT phosphorylation sites from murine brain.";
RL J. Proteome Res. 7:311-318(2008).
RN [8]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-330; SER-331; SER-333;
RP THR-336; THR-337 AND SER-404, AND IDENTIFICATION BY MASS SPECTROMETRY
RP [LARGE SCALE ANALYSIS].
RC TISSUE=Brain, Heart, Lung, and Spleen;
RX PubMed=21183079; DOI=10.1016/j.cell.2010.12.001;
RA Huttlin E.L., Jedrychowski M.P., Elias J.E., Goswami T., Rad R.,
RA Beausoleil S.A., Villen J., Haas W., Sowa M.E., Gygi S.P.;
RT "A tissue-specific atlas of mouse protein phosphorylation and expression.";
RL Cell 143:1174-1189(2010).
RN [9]
RP FUNCTION, AND MUTAGENESIS OF THR-286.
RX PubMed=23805378; DOI=10.7554/elife.00518;
RA Tao L., Xie Q., Ding Y.H., Li S.T., Peng S., Zhang Y.P., Tan D., Yuan Z.,
RA Dong M.Q.;
RT "CAMKII and Calcineurin regulate the lifespan of Caenorhabditis elegans
RT through the FOXO transcription factor DAF-16.";
RL Elife 2:E00518-E00518(2013).
RN [10]
RP FUNCTION, CATALYTIC ACTIVITY, INTERACTION WITH DAGLA, AND MUTAGENESIS OF
RP THR-286.
RX PubMed=23502535; DOI=10.1038/nn.3353;
RA Shonesy B.C., Wang X., Rose K.L., Ramikie T.S., Cavener V.S., Rentz T.,
RA Baucum A.J. II, Jalan-Sakrikar N., Mackie K., Winder D.G., Patel S.,
RA Colbran R.J.;
RT "CaMKII regulates diacylglycerol lipase-alpha and striatal endocannabinoid
RT signaling.";
RL Nat. Neurosci. 16:456-463(2013).
RN [11]
RP PHOSPHORYLATION AT THR-286, AND MUTAGENESIS OF GLU-183.
RX PubMed=28130356; DOI=10.1523/jneurosci.2068-16.2017;
RA Stephenson J.R., Wang X., Perfitt T.L., Parrish W.P., Shonesy B.C.,
RA Marks C.R., Mortlock D.P., Nakagawa T., Sutcliffe J.S., Colbran R.J.;
RT "Mutation Disrupts Dendritic Morphology and Synaptic Transmission, and
RT Causes ASD-Related Behaviors.";
RL J. Neurosci. 37:2216-2233(2017).
RN [12]
RP SUBCELLULAR LOCATION.
RX PubMed=28642476; DOI=10.1038/s41598-017-04355-8;
RA Vigil F.A., Mizuno K., Lucchesi W., Valls-Comamala V., Giese K.P.;
RT "Prevention of long-term memory loss after retrieval by an endogenous
RT CaMKII inhibitor.";
RL Sci. Rep. 7:4040-4040(2017).
CC -!- FUNCTION: Calcium/calmodulin-dependent protein kinase that functions
CC autonomously after Ca(2+)/calmodulin-binding and autophosphorylation,
CC and is involved in synaptic plasticity, neurotransmitter release and
CC long-term potentiation. Member of the NMDAR signaling complex in
CC excitatory synapses, it regulates NMDAR-dependent potentiation of the
CC AMPAR and therefore excitatory synaptic transmission (By similarity).
CC Regulates dendritic spine development. Also regulates the migration of
CC developing neurons (By similarity). Phosphorylates the transcription
CC factor FOXO3 to activate its transcriptional activity
CC (PubMed:23805378). Acts as a negative regulator of 2-
CC arachidonoylglycerol (2-AG)-mediated synaptic signaling via modulation
CC of DAGLA activity (PubMed:23502535). {ECO:0000250|UniProtKB:P11275,
CC ECO:0000250|UniProtKB:Q9UQM7, ECO:0000269|PubMed:23502535,
CC ECO:0000269|PubMed:23805378}.
CC -!- FUNCTION: [Isoform Alpha KAP]: Has no kinase activity.
CC {ECO:0000269|PubMed:8524307}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=ATP + L-seryl-[protein] = ADP + H(+) + O-phospho-L-seryl-
CC [protein]; Xref=Rhea:RHEA:17989, Rhea:RHEA-COMP:9863, Rhea:RHEA-
CC COMP:11604, ChEBI:CHEBI:15378, ChEBI:CHEBI:29999, ChEBI:CHEBI:30616,
CC ChEBI:CHEBI:83421, ChEBI:CHEBI:456216; EC=2.7.11.17;
CC Evidence={ECO:0000269|PubMed:23502535};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=ATP + L-threonyl-[protein] = ADP + H(+) + O-phospho-L-
CC threonyl-[protein]; Xref=Rhea:RHEA:46608, Rhea:RHEA-COMP:11060,
CC Rhea:RHEA-COMP:11605, ChEBI:CHEBI:15378, ChEBI:CHEBI:30013,
CC ChEBI:CHEBI:30616, ChEBI:CHEBI:61977, ChEBI:CHEBI:456216;
CC EC=2.7.11.17; Evidence={ECO:0000269|PubMed:23502535};
CC -!- COFACTOR:
CC Name=Mg(2+); Xref=ChEBI:CHEBI:18420;
CC Evidence={ECO:0000250|UniProtKB:Q9UQM7};
CC -!- ACTIVITY REGULATION: Activated by Ca(2+)/calmodulin. Binding of
CC calmodulin results in conformational change that relieves intrasteric
CC autoinhibition and allows autophosphorylation of Thr-286 which turns
CC the kinase in a constitutively active form and confers to the kinase a
CC Ca(2+)-independent activity. {ECO:0000250|UniProtKB:Q9UQM7}.
CC -!- SUBUNIT: There are 4 genes encoding calcium/calmodulin-dependent
CC protein kinase type II chains: CAMK2A, CAMK2B, CAMK2G and CAMK2D. The
CC corresponding proteins assemble into homo- or heteromultimeric
CC holoenzymes composed of 12 subunits with two hexameric rings stacked
CC one on top of the other (By similarity). Interacts with BAALC.
CC Interacts with MPDZ. Interacts with SYN1. Interacts with CAMK2N2.
CC Interacts with SYNGAP1. Interacts with SYNPO2 (By similarity).
CC Interacts with SHANK3. Interacts with GRIN2B. Interacts with CACNB2.
CC Interacts with LRRC7. Interacts with GRM5 (By similarity). Interacts
CC with DAGLA (via C-terminal); this interaction is enhanced by
CC autophosphorylation of CAMK2A at Thr-286 (PubMed:23502535). Interacts
CC with CAMK2N1; this interaction requires CAMK2A activation by Ca(2+) (By
CC similarity). {ECO:0000250|UniProtKB:P11275,
CC ECO:0000250|UniProtKB:Q9UQM7, ECO:0000269|PubMed:23502535}.
CC -!- INTERACTION:
CC P11798; Q9JI91: Actn2; NbExp=3; IntAct=EBI-400384, EBI-299169;
CC P11798; Q62108: Dlg4; NbExp=4; IntAct=EBI-400384, EBI-300895;
CC P11798; Q01097: Grin2b; NbExp=5; IntAct=EBI-400384, EBI-400125;
CC P11798; Q00960: Grin2b; Xeno; NbExp=4; IntAct=EBI-400384, EBI-396905;
CC P11798; P70587: Lrrc7; Xeno; NbExp=2; IntAct=EBI-400384, EBI-7798464;
CC P11798-2; Q9Z1R2: Bag6; NbExp=3; IntAct=EBI-400402, EBI-644645;
CC -!- SUBCELLULAR LOCATION: [Isoform Alpha KAP]: Cytoplasm
CC {ECO:0000305|PubMed:8524307}.
CC -!- SUBCELLULAR LOCATION: Synapse {ECO:0000269|PubMed:28642476}.
CC Postsynaptic density {ECO:0000250|UniProtKB:P11275}. Cell projection,
CC dendritic spine {ECO:0000250|UniProtKB:Q9UQM7}. Cell projection,
CC dendrite {ECO:0000250|UniProtKB:Q9UQM7}. Note=Postsynaptic lipid rafts.
CC {ECO:0000250|UniProtKB:P11275}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=Alpha CaMKII;
CC IsoId=P11798-1; Sequence=Displayed;
CC Name=Alpha KAP {ECO:0000303|PubMed:8524307};
CC IsoId=P11798-2; Sequence=VSP_004767, VSP_004768, VSP_004769;
CC -!- TISSUE SPECIFICITY: [Isoform Alpha CaMKII]: Expressed in brain.
CC {ECO:0000269|PubMed:8524307}.
CC -!- TISSUE SPECIFICITY: [Isoform Alpha KAP]: Expressed in skeletal muscle.
CC {ECO:0000269|PubMed:8524307}.
CC -!- PTM: Autophosphorylation of Thr-286 following activation by
CC Ca(2+)/calmodulin. Phosphorylation of Thr-286 locks the kinase into an
CC activated state. {ECO:0000269|PubMed:28130356}.
CC -!- PTM: Palmitoylated. Probably palmitoylated by ZDHHC3 and ZDHHC7.
CC {ECO:0000250|UniProtKB:P11275}.
CC -!- SIMILARITY: Belongs to the protein kinase superfamily. CAMK Ser/Thr
CC protein kinase family. CaMK subfamily. {ECO:0000305}.
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DR EMBL; X14836; CAA32946.1; -; mRNA.
DR EMBL; X87142; CAA60620.1; -; mRNA.
DR EMBL; AK083245; BAC38829.1; -; mRNA.
DR EMBL; BC031745; AAH31745.1; -; mRNA.
DR CCDS; CCDS29276.1; -. [P11798-1]
DR CCDS; CCDS29277.1; -. [P11798-2]
DR PIR; JC6083; JC6083.
DR PIR; S04365; S04365.
DR RefSeq; NP_001273738.1; NM_001286809.1.
DR RefSeq; NP_033922.1; NM_009792.3. [P11798-2]
DR RefSeq; NP_803126.1; NM_177407.4. [P11798-1]
DR PDB; 1HKX; X-ray; 2.65 A; A/B/C/D/E/F/G/H/I/J/K/L/M/N=336-478.
DR PDB; 4X3I; X-ray; 1.80 A; B=309-315.
DR PDB; 6TS3; X-ray; 1.28 A; C/D=294-315.
DR PDBsum; 1HKX; -.
DR PDBsum; 4X3I; -.
DR PDBsum; 6TS3; -.
DR AlphaFoldDB; P11798; -.
DR SMR; P11798; -.
DR BioGRID; 198461; 37.
DR DIP; DIP-31593N; -.
DR IntAct; P11798; 51.
DR MINT; P11798; -.
DR STRING; 10090.ENSMUSP00000099952; -.
DR GuidetoPHARMACOLOGY; 1555; -.
DR iPTMnet; P11798; -.
DR PhosphoSitePlus; P11798; -.
DR SwissPalm; P11798; -.
DR jPOST; P11798; -.
DR MaxQB; P11798; -.
DR PaxDb; P11798; -.
DR PeptideAtlas; P11798; -.
DR PRIDE; P11798; -.
DR ProteomicsDB; 263582; -. [P11798-1]
DR ProteomicsDB; 263583; -. [P11798-2]
DR Antibodypedia; 3814; 903 antibodies from 52 providers.
DR DNASU; 12322; -.
DR Ensembl; ENSMUST00000102888; ENSMUSP00000099952; ENSMUSG00000024617. [P11798-1]
DR Ensembl; ENSMUST00000115295; ENSMUSP00000110950; ENSMUSG00000024617. [P11798-2]
DR GeneID; 12322; -.
DR KEGG; mmu:12322; -.
DR UCSC; uc008fbg.2; mouse. [P11798-1]
DR UCSC; uc008fbh.2; mouse. [P11798-2]
DR CTD; 815; -.
DR MGI; MGI:88256; Camk2a.
DR VEuPathDB; HostDB:ENSMUSG00000024617; -.
DR eggNOG; KOG0033; Eukaryota.
DR GeneTree; ENSGT00940000155150; -.
DR HOGENOM; CLU_000288_71_0_1; -.
DR InParanoid; P11798; -.
DR OMA; SEETCIW; -.
DR OrthoDB; 1391910at2759; -.
DR TreeFam; TF315229; -.
DR BRENDA; 2.7.11.17; 3474.
DR Reactome; R-MMU-3371571; HSF1-dependent transactivation.
DR Reactome; R-MMU-4086398; Ca2+ pathway.
DR Reactome; R-MMU-438066; Unblocking of NMDA receptors, glutamate binding and activation.
DR Reactome; R-MMU-5576892; Phase 0 - rapid depolarisation.
DR Reactome; R-MMU-5578775; Ion homeostasis.
DR Reactome; R-MMU-5673000; RAF activation.
DR Reactome; R-MMU-5673001; RAF/MAP kinase cascade.
DR Reactome; R-MMU-877300; Interferon gamma signaling.
DR Reactome; R-MMU-936837; Ion transport by P-type ATPases.
DR BioGRID-ORCS; 12322; 2 hits in 74 CRISPR screens.
DR ChiTaRS; Camk2a; mouse.
DR EvolutionaryTrace; P11798; -.
DR PRO; PR:P11798; -.
DR Proteomes; UP000000589; Chromosome 18.
DR RNAct; P11798; protein.
DR Bgee; ENSMUSG00000024617; Expressed in dentate gyrus of hippocampal formation granule cell and 174 other tissues.
DR ExpressionAtlas; P11798; baseline and differential.
DR Genevisible; P11798; MM.
DR GO; GO:0070161; C:anchoring junction; IEA:UniProtKB-KW.
DR GO; GO:0030424; C:axon; ISO:MGI.
DR GO; GO:0005954; C:calcium- and calmodulin-dependent protein kinase complex; ISS:UniProtKB.
DR GO; GO:0005737; C:cytoplasm; IBA:GO_Central.
DR GO; GO:0005829; C:cytosol; ISO:MGI.
DR GO; GO:0030425; C:dendrite; ISO:MGI.
DR GO; GO:0032839; C:dendrite cytoplasm; ISO:MGI.
DR GO; GO:0043197; C:dendritic spine; ISS:UniProtKB.
DR GO; GO:0099573; C:glutamatergic postsynaptic density; ISO:MGI.
DR GO; GO:0098978; C:glutamatergic synapse; ISO:MGI.
DR GO; GO:0016020; C:membrane; ISO:MGI.
DR GO; GO:0005739; C:mitochondrion; IDA:BHF-UCL.
DR GO; GO:0043005; C:neuron projection; IBA:GO_Central.
DR GO; GO:0043025; C:neuronal cell body; ISO:MGI.
DR GO; GO:0005634; C:nucleus; ISO:MGI.
DR GO; GO:0099524; C:postsynaptic cytosol; ISO:MGI.
DR GO; GO:0014069; C:postsynaptic density; IDA:MGI.
DR GO; GO:0099634; C:postsynaptic specialization membrane; IEA:GOC.
DR GO; GO:0099523; C:presynaptic cytosol; ISO:MGI.
DR GO; GO:0098685; C:Schaffer collateral - CA1 synapse; IDA:SynGO.
DR GO; GO:0045202; C:synapse; IDA:UniProtKB.
DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
DR GO; GO:0009931; F:calcium-dependent protein serine/threonine kinase activity; IDA:CAFA.
DR GO; GO:0005516; F:calmodulin binding; IDA:CAFA.
DR GO; GO:0004683; F:calmodulin-dependent protein kinase activity; IDA:CAFA.
DR GO; GO:0035254; F:glutamate receptor binding; IPI:MGI.
DR GO; GO:0032794; F:GTPase activating protein binding; ISO:MGI.
DR GO; GO:0042802; F:identical protein binding; ISO:MGI.
DR GO; GO:0016301; F:kinase activity; ISO:MGI.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0042803; F:protein homodimerization activity; ISO:MGI.
DR GO; GO:0106310; F:protein serine kinase activity; IEA:RHEA.
DR GO; GO:0004674; F:protein serine/threonine kinase activity; IDA:MGI.
DR GO; GO:0038166; P:angiotensin-activated signaling pathway; ISO:MGI.
DR GO; GO:0006816; P:calcium ion transport; IMP:MGI.
DR GO; GO:0099004; P:calmodulin dependent kinase signaling pathway; ISO:MGI.
DR GO; GO:0048813; P:dendrite morphogenesis; IMP:MGI.
DR GO; GO:0060996; P:dendritic spine development; ISS:UniProtKB.
DR GO; GO:0000082; P:G1/S transition of mitotic cell cycle; IMP:MGI.
DR GO; GO:0035235; P:ionotropic glutamate receptor signaling pathway; ISO:MGI.
DR GO; GO:0051346; P:negative regulation of hydrolase activity; IMP:UniProtKB.
DR GO; GO:0098989; P:NMDA selective glutamate receptor signaling pathway; ISO:MGI.
DR GO; GO:0018105; P:peptidyl-serine phosphorylation; IDA:CAFA.
DR GO; GO:1990443; P:peptidyl-threonine autophosphorylation; IMP:UniProtKB.
DR GO; GO:0051928; P:positive regulation of calcium ion transport; IMP:MGI.
DR GO; GO:0010666; P:positive regulation of cardiac muscle cell apoptotic process; IMP:MGI.
DR GO; GO:0051092; P:positive regulation of NF-kappaB transcription factor activity; ISO:MGI.
DR GO; GO:0098970; P:postsynaptic neurotransmitter receptor diffusion trapping; ISO:MGI.
DR GO; GO:0046777; P:protein autophosphorylation; IMP:MGI.
DR GO; GO:0006468; P:protein phosphorylation; ISO:MGI.
DR GO; GO:2000124; P:regulation of endocannabinoid signaling pathway; IMP:UniProtKB.
DR GO; GO:1902108; P:regulation of mitochondrial membrane permeability involved in apoptotic process; IMP:MGI.
DR GO; GO:2001222; P:regulation of neuron migration; ISS:UniProtKB.
DR GO; GO:0048168; P:regulation of neuronal synaptic plasticity; IMP:MGI.
DR GO; GO:0098696; P:regulation of neurotransmitter receptor localization to postsynaptic specialization membrane; ISO:MGI.
DR GO; GO:0046928; P:regulation of neurotransmitter secretion; IMP:MGI.
DR GO; GO:1903076; P:regulation of protein localization to plasma membrane; ISO:MGI.
DR GO; GO:0099148; P:regulation of synaptic vesicle docking; IDA:SynGO.
DR GO; GO:0002931; P:response to ischemia; IMP:MGI.
DR InterPro; IPR013543; Ca/CaM-dep_prot_kinase-assoc.
DR InterPro; IPR011009; Kinase-like_dom_sf.
DR InterPro; IPR032710; NTF2-like_dom_sf.
DR InterPro; IPR000719; Prot_kinase_dom.
DR InterPro; IPR017441; Protein_kinase_ATP_BS.
DR InterPro; IPR008271; Ser/Thr_kinase_AS.
DR Pfam; PF08332; CaMKII_AD; 1.
DR Pfam; PF00069; Pkinase; 1.
DR SMART; SM00220; S_TKc; 1.
DR SUPFAM; SSF54427; SSF54427; 1.
DR SUPFAM; SSF56112; SSF56112; 1.
DR PROSITE; PS00107; PROTEIN_KINASE_ATP; 1.
DR PROSITE; PS50011; PROTEIN_KINASE_DOM; 1.
DR PROSITE; PS00108; PROTEIN_KINASE_ST; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Alternative splicing; ATP-binding; Calmodulin-binding;
KW Cell projection; Cytoplasm; Direct protein sequencing; Kinase; Lipoprotein;
KW Magnesium; Metal-binding; Nucleotide-binding; Palmitate; Phosphoprotein;
KW Reference proteome; Serine/threonine-protein kinase; Synapse; Transferase.
FT CHAIN 1..478
FT /note="Calcium/calmodulin-dependent protein kinase type II
FT subunit alpha"
FT /id="PRO_0000086092"
FT DOMAIN 13..271
FT /note="Protein kinase"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT REGION 290..300
FT /note="Calmodulin-binding"
FT REGION 310..320
FT /note="Interaction with BAALC"
FT /evidence="ECO:0000250"
FT REGION 314..341
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 322..341
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT ACT_SITE 135
FT /note="Proton acceptor"
FT BINDING 19..27
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT BINDING 42
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT MOD_RES 13
FT /note="Phosphotyrosine"
FT /evidence="ECO:0007744|PubMed:18034455"
FT MOD_RES 257
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P11275"
FT MOD_RES 286
FT /note="Phosphothreonine; by autocatalysis"
FT /evidence="ECO:0000269|PubMed:28130356"
FT MOD_RES 330
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:21183079"
FT MOD_RES 331
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:21183079"
FT MOD_RES 333
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:21183079"
FT MOD_RES 336
FT /note="Phosphothreonine"
FT /evidence="ECO:0007744|PubMed:21183079"
FT MOD_RES 337
FT /note="Phosphothreonine"
FT /evidence="ECO:0007744|PubMed:21183079"
FT MOD_RES 404
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:21183079"
FT VAR_SEQ 1..289
FT /note="Missing (in isoform Alpha KAP)"
FT /evidence="ECO:0000303|PubMed:8524307"
FT /id="VSP_004767"
FT VAR_SEQ 290..314
FT /note="LKKFNARRKLKGAILTTMLATRNFS -> MLLFLTLWALVPCLVLLTLYFLS
FT ST (in isoform Alpha KAP)"
FT /evidence="ECO:0000303|PubMed:8524307"
FT /id="VSP_004768"
FT VAR_SEQ 328
FT /note="K -> KKRKSSSSVQLM (in isoform Alpha KAP)"
FT /evidence="ECO:0000303|PubMed:8524307"
FT /id="VSP_004769"
FT MUTAGEN 183
FT /note="E->V: Decreased protein abundance. Decreased
FT autophosphorylation. Changed subcellular localization.
FT Homozygous mice for that mutation are hyperactive and
FT display repetitive behaviors. They also display social
FT deficits and decreased exploratory behavior."
FT /evidence="ECO:0000269|PubMed:28130356"
FT MUTAGEN 286
FT /note="T->A: Abolishes autophosphorylation. Loss of FOXO3
FT activation. Reduces association with DAGLA. Enhances DAGLA
FT enzymatic activity with an increase of 2-AG levels in
FT dorsolateral striatal tissue of knockin mice. Inhibition of
FT 2-AG breakdown using JZL-184 decreased locomotor activity
FT in knockin mice."
FT /evidence="ECO:0000269|PubMed:23502535,
FT ECO:0000269|PubMed:23805378"
FT MUTAGEN 286
FT /note="T->D: Phosphomimetic mutant. Enhanced FOXO3
FT activation."
FT /evidence="ECO:0000269|PubMed:23805378"
FT CONFLICT 40
FT /note="A -> P (in Ref. 1; CAA32946)"
FT /evidence="ECO:0000305"
FT CONFLICT 169
FT /note="A -> R (in Ref. 1; CAA32946)"
FT /evidence="ECO:0000305"
FT CONFLICT 228
FT /note="G -> R (in Ref. 1; CAA32946)"
FT /evidence="ECO:0000305"
FT HELIX 295..309
FT /evidence="ECO:0007829|PDB:6TS3"
FT STRAND 310..313
FT /evidence="ECO:0007829|PDB:4X3I"
FT TURN 338..340
FT /evidence="ECO:0007829|PDB:1HKX"
FT HELIX 341..362
FT /evidence="ECO:0007829|PDB:1HKX"
FT HELIX 366..372
FT /evidence="ECO:0007829|PDB:1HKX"
FT STRAND 373..380
FT /evidence="ECO:0007829|PDB:1HKX"
FT HELIX 382..384
FT /evidence="ECO:0007829|PDB:1HKX"
FT STRAND 389..392
FT /evidence="ECO:0007829|PDB:1HKX"
FT HELIX 393..400
FT /evidence="ECO:0007829|PDB:1HKX"
FT HELIX 404..406
FT /evidence="ECO:0007829|PDB:1HKX"
FT STRAND 410..421
FT /evidence="ECO:0007829|PDB:1HKX"
FT STRAND 423..437
FT /evidence="ECO:0007829|PDB:1HKX"
FT STRAND 445..458
FT /evidence="ECO:0007829|PDB:1HKX"
FT STRAND 461..472
FT /evidence="ECO:0007829|PDB:1HKX"
SQ SEQUENCE 478 AA; 54115 MW; 306F416CCE9B5F62 CRC64;
MATITCTRFT EEYQLFEELG KGAFSVVRRC VKVLAGQEYA AKIINTKKLS ARDHQKLERE
ARICRLLKHP NIVRLHDSIS EEGHHYLIFD LVTGGELFED IVAREYYSEA DASHCIQQIL
EAVLHCHQMG VVHRDLKPEN LLLASKLKGA AVKLADFGLA IEVEGEQQAW FGFAGTPGYL
SPEVLRKDPY GKPVDLWACG VILYILLVGY PPFWDEDQHR LYQQIKAGAY DFPSPEWDTV
TPEAKDLINK MLTINPSKRI TAAEALKHPW ISHRSTVASC MHRQETVDCL KKFNARRKLK
GAILTTMLAT RNFSGGKSGG NKKNDGVKES SESTNTTIED EDTKVRKQEI IKVTEQLIEA
ISNGDFESYT KMCDPGMTAF EPEALGNLVE GLDFHRFYFE NLWSRNSKPV HTTILNPHIH
LMGDESACIA YIRITQYLDA GGIPRTAQSE ETRVWHRRDG KWQIVHFHRS GAPSVLPH
