CK2N1_MOUSE
ID CK2N1_MOUSE Reviewed; 78 AA.
AC Q6QWF9;
DT 10-JUN-2008, integrated into UniProtKB/Swiss-Prot.
DT 05-JUL-2004, sequence version 1.
DT 03-AUG-2022, entry version 110.
DE RecName: Full=Calcium/calmodulin-dependent protein kinase II inhibitor 1;
DE AltName: Full=calcium/calmodulin-dependent protein kinase II inhibitor alpha;
DE Short=mCaMKIINalpha;
GN Name=Camk2n1;
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], AND INDUCTION.
RC STRAIN=SWR/J;
RX PubMed=17010311; DOI=10.1016/j.bbrc.2006.09.066;
RA Saha S., Ramanathan A., Rangarajan P.N.;
RT "Regulation of Ca2+/calmodulin kinase II inhibitor alpha (CaMKIINalpha) in
RT virus-infected mouse brain.";
RL Biochem. Biophys. Res. Commun. 350:444-449(2006).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=C57BL/6J;
RX PubMed=19468303; DOI=10.1371/journal.pbio.1000112;
RA Church D.M., Goodstadt L., Hillier L.W., Zody M.C., Goldstein S., She X.,
RA Bult C.J., Agarwala R., Cherry J.L., DiCuccio M., Hlavina W., Kapustin Y.,
RA Meric P., Maglott D., Birtle Z., Marques A.C., Graves T., Zhou S.,
RA Teague B., Potamousis K., Churas C., Place M., Herschleb J., Runnheim R.,
RA Forrest D., Amos-Landgraf J., Schwartz D.C., Cheng Z., Lindblad-Toh K.,
RA Eichler E.E., Ponting C.P.;
RT "Lineage-specific biology revealed by a finished genome assembly of the
RT mouse.";
RL PLoS Biol. 7:E1000112-E1000112(2009).
RN [3]
RP INDUCTION.
RX PubMed=16819996; DOI=10.1111/j.1460-9568.2006.04830.x;
RA Lepicard E.M., Mizuno K., Antunes-Martins A., von Hertzen L.S., Giese K.P.;
RT "An endogenous inhibitor of calcium/calmodulin-dependent kinase II is up-
RT regulated during consolidation of fear memory.";
RL Eur. J. Neurosci. 23:3063-3070(2006).
RN [4]
RP TISSUE SPECIFICITY, AND SUBCELLULAR LOCATION.
RX PubMed=17350603; DOI=10.1016/j.brainres.2007.02.018;
RA Saha S., Datta K., Rangarajan P.;
RT "Characterization of mouse neuronal Ca2+/calmodulin kinase II inhibitor
RT alpha.";
RL Brain Res. 1148:38-42(2007).
RN [5]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Brain;
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 [6]
RP FUNCTION, SUBCELLULAR LOCATION, INDUCTION BY MEMORY RETRIEVAL, AND
RP DISRUPTION PHENOTYPE.
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).
RN [7]
RP FUNCTION.
RX PubMed=31327268; DOI=10.1161/hypertensionaha.118.12409;
RA Alfazema N., Barrier M., de Proce S.M., Menzies R.I., Carter R.,
RA Stewart K., Diaz A.G., Moyon B., Webster Z., Bellamy C.O.C., Arends M.J.,
RA Stimson R.H., Morton N.M., Aitman T.J., Coan P.M.;
RT "Camk2n1 Is a Negative Regulator of Blood Pressure, Left Ventricular Mass,
RT Insulin Sensitivity, and Promotes Adiposity.";
RL Hypertension 74:687-696(2019).
RN [8]
RP FUNCTION, TISSUE SPECIFICITY, AND DISRUPTION PHENOTYPE.
RX PubMed=33746041; DOI=10.1016/j.freeradbiomed.2021.03.014;
RA Wei Z., Fei Y., Wang Q., Hou J., Cai X., Yang Y., Chen T., Xu Q., Wang Y.,
RA Li Y.G.;
RT "Loss of Camk2n1 aggravates cardiac remodeling and malignant ventricular
RT arrhythmia after myocardial infarction in mice via NLRP3 inflammasome
RT activation.";
RL Free Radic. Biol. Med. 167:243-257(2021).
CC -!- FUNCTION: Potent and specific inhibitor of CaM-kinase II (CAMK2) (By
CC similarity). Plays a role in the maintenance of long-term retrieval-
CC induced memory in response to contextual fear (PubMed:28642476).
CC Modulates blood pressure and vascular reactivity via regulation of
CC CAMK2 activity in addition to regulation of left ventricular mass (By
CC similarity). Mediates the NLRP3 inflammasome in cardiomyocytes via
CC acting as an inhibitor of the MAPK14/p38 and MAPK8/JNK pathways,
CC thereby regulating ventricular remodeling and cardiac rhythm post-
CC myocardial infarction (PubMed:33746041). Negatively effects insulin
CC sensitivity and promotes lipid formation in adipose tissues independent
CC of CAMK2 signaling (PubMed:31327268). {ECO:0000250|UniProtKB:Q9JI15,
CC ECO:0000269|PubMed:28642476, ECO:0000269|PubMed:31327268,
CC ECO:0000269|PubMed:33746041}.
CC -!- SUBUNIT: Interacts with CAMK2B; the presence of Ca(2+)/calmodulin
CC increases the interaction but is not essential (By similarity).
CC Interacts with CAMK2A; this interaction requires CAMK2A activation by
CC Ca(2+) (By similarity). {ECO:0000250|UniProtKB:Q9JI15}.
CC -!- SUBCELLULAR LOCATION: Synapse {ECO:0000269|PubMed:17350603,
CC ECO:0000269|PubMed:28642476}. Cell projection, dendrite
CC {ECO:0000250|UniProtKB:Q9JI15}. Postsynaptic density
CC {ECO:0000269|PubMed:17350603}.
CC -!- TISSUE SPECIFICITY: Expressed in the brain (at protein level)
CC (PubMed:17350603). Expressed in cardiomyocytes but not cardiac
CC fibroblasts (at protein level) (PubMed:33746041).
CC {ECO:0000269|PubMed:17350603, ECO:0000269|PubMed:33746041}.
CC -!- INDUCTION: Up-regulated during retrieval and consolidation of fear
CC memory (PubMed:16819996, PubMed:28642476). Down-regulated in brain
CC during Japanese encephalitis virus (JEV) and rabies virus infection
CC (PubMed:17010311). {ECO:0000269|PubMed:16819996,
CC ECO:0000269|PubMed:17010311, ECO:0000269|PubMed:28642476}.
CC -!- DISRUPTION PHENOTYPE: Knockout mice show normal growth rates
CC (PubMed:33746041). Increased expression of inflammatory markers and
CC enhanced recruitment of macrophages to the cardiac infarct border 3
CC days post-myocardial infarction (MI) (PubMed:33746041). Increased
CC infarct size, interstitial fibrosis, and area of cardiac hypertrophy,
CC leading to decreased left ventricular ejection fractions, fractional
CC shortening and increased spontaneous ventricular arrhythmia at 28 days
CC post MI (PubMed:33746041). Overall survival of mice following MI was
CC significantly decreased (PubMed:33746041). In hippocampal knockdown
CC mice, long-term retrieval-induced memory in response to contextual fear
CC is impaired (PubMed:28642476). Increase in Camk2a T-296
CC autophosphorylation and Gria1/GluA1 abundance following conditioning
CC and long-term memory retrieval (PubMed:28642476).
CC {ECO:0000269|PubMed:28642476, ECO:0000269|PubMed:33746041}.
CC -!- SIMILARITY: Belongs to the CAMK2N family. {ECO:0000305}.
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DR EMBL; AY523601; AAS02090.1; -; mRNA.
DR EMBL; AL807249; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR CCDS; CCDS38930.1; -.
DR RefSeq; NP_079727.1; NM_025451.2.
DR AlphaFoldDB; Q6QWF9; -.
DR SMR; Q6QWF9; -.
DR STRING; 10090.ENSMUSP00000060349; -.
DR iPTMnet; Q6QWF9; -.
DR PhosphoSitePlus; Q6QWF9; -.
DR MaxQB; Q6QWF9; -.
DR PaxDb; Q6QWF9; -.
DR PRIDE; Q6QWF9; -.
DR ProteomicsDB; 285453; -.
DR Antibodypedia; 53235; 77 antibodies from 17 providers.
DR Ensembl; ENSMUST00000050918; ENSMUSP00000060349; ENSMUSG00000046447.
DR GeneID; 66259; -.
DR KEGG; mmu:66259; -.
DR UCSC; uc008vkz.2; mouse.
DR CTD; 55450; -.
DR MGI; MGI:1913509; Camk2n1.
DR VEuPathDB; HostDB:ENSMUSG00000046447; -.
DR eggNOG; ENOG502S6QW; Eukaryota.
DR GeneTree; ENSGT00390000004940; -.
DR HOGENOM; CLU_197183_0_0_1; -.
DR InParanoid; Q6QWF9; -.
DR OMA; NEQKNGT; -.
DR OrthoDB; 1637105at2759; -.
DR PhylomeDB; Q6QWF9; -.
DR TreeFam; TF333175; -.
DR BioGRID-ORCS; 66259; 2 hits in 72 CRISPR screens.
DR ChiTaRS; Camk2n1; mouse.
DR PRO; PR:Q6QWF9; -.
DR Proteomes; UP000000589; Chromosome 4.
DR RNAct; Q6QWF9; protein.
DR Bgee; ENSMUSG00000046447; Expressed in prefrontal cortex and 209 other tissues.
DR Genevisible; Q6QWF9; MM.
DR GO; GO:0070161; C:anchoring junction; IEA:UniProtKB-KW.
DR GO; GO:0030425; C:dendrite; ISO:MGI.
DR GO; GO:0043025; C:neuronal cell body; ISO:MGI.
DR GO; GO:0014069; C:postsynaptic density; IDA:MGI.
DR GO; GO:0045202; C:synapse; IDA:UniProtKB.
DR GO; GO:0008427; F:calcium-dependent protein kinase inhibitor activity; ISO:MGI.
DR GO; GO:0019901; F:protein kinase binding; ISO:MGI.
DR GO; GO:0004860; F:protein kinase inhibitor activity; IDA:MGI.
DR GO; GO:0055074; P:calcium ion homeostasis; ISO:MGI.
DR GO; GO:0007616; P:long-term memory; IMP:UniProtKB.
DR GO; GO:0006469; P:negative regulation of protein kinase activity; IBA:GO_Central.
DR GO; GO:0050729; P:positive regulation of inflammatory response; IDA:UniProtKB.
DR GO; GO:0035774; P:positive regulation of insulin secretion involved in cellular response to glucose stimulus; ISO:MGI.
DR GO; GO:0003084; P:positive regulation of systemic arterial blood pressure; ISO:MGI.
DR InterPro; IPR026779; Camk2n.
DR PANTHER; PTHR31007; PTHR31007; 1.
DR Pfam; PF15170; CaM-KIIN; 1.
PE 1: Evidence at protein level;
KW Cell projection; Protein kinase inhibitor; Reference proteome; Synapse.
FT CHAIN 1..78
FT /note="Calcium/calmodulin-dependent protein kinase II
FT inhibitor 1"
FT /id="PRO_0000338394"
FT REGION 41..68
FT /note="CAMK2 inhibitory domain"
FT /evidence="ECO:0000250"
SQ SEQUENCE 78 AA; 8513 MW; A89A9E5DA11B8E61 CRC64;
MSEVLPYGDE KLSPYGDGGD VGQIFSCRLQ DTNNFFGAGQ SKRPPKLGQI GRSKRVVIED
DRIDDVLKTM TDKAPPGV
