CK2N1_RAT
ID CK2N1_RAT Reviewed; 78 AA.
AC Q9JI15;
DT 10-JUN-2008, integrated into UniProtKB/Swiss-Prot.
DT 01-OCT-2000, sequence version 1.
DT 03-AUG-2022, entry version 111.
DE RecName: Full=Calcium/calmodulin-dependent protein kinase II inhibitor 1;
DE AltName: Full=calcium/calmodulin-dependent protein kinase II inhibitor alpha;
DE Short=CaM-KIINalpha;
DE Short=CaMKIINalpha;
GN Name=Camk2n1;
OS Rattus norvegicus (Rat).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Rattus.
OX NCBI_TaxID=10116;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, INTERACTION WITH CAMK2A AND CAMK2B,
RP SUBCELLULAR LOCATION, TISSUE SPECIFICITY, AND MUTAGENESIS OF ARG-43; ILE-58
RP AND 59-LYS--ALA-61.
RX PubMed=11182241; DOI=10.1016/s0306-4522(00)00520-0;
RA Chang B.H., Mukherji S., Soderling T.R.;
RT "Calcium/calmodulin-dependent protein kinase II inhibitor protein:
RT localization of isoforms in rat brain.";
RL Neuroscience 102:767-777(2001).
RN [2]
RP FUNCTION, AND DISRUPTION PHENOTYPE.
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).
CC -!- FUNCTION: Potent and specific inhibitor of CaM-kinase II (CAMK2)
CC (PubMed:11182241). Plays a role in the maintenance of long-term
CC retrieval-induced memory in response to contextual fear (By
CC similarity). Modulates blood pressure and vascular reactivity via
CC regulation of CAMK2 activity in addition to regulation of left
CC ventricular mass (PubMed:31327268). Mediates the NLRP3 inflammasome in
CC cardiomyocytes via acting as an inhibitor of the MAPK14/p38 and
CC MAPK8/JNK pathways, thereby regulating ventricular remodeling and
CC cardiac rhythm post-myocardial infarction (By similarity). Negatively
CC effects insulin sensitivity and promotes lipid formation in adipose
CC tissues independent of CAMK2 signaling (PubMed:31327268).
CC {ECO:0000250|UniProtKB:Q6QWF9, ECO:0000269|PubMed:11182241,
CC ECO:0000269|PubMed:31327268}.
CC -!- SUBUNIT: Interacts with CAMK2B; the presence of Ca(2+)/calmodulin
CC increases the interaction but is not essential (PubMed:11182241).
CC Interacts with CAMK2A; this interaction requires CAMK2A activation by
CC Ca(2+) (PubMed:11182241). {ECO:0000269|PubMed:11182241}.
CC -!- SUBCELLULAR LOCATION: Synapse {ECO:0000250|UniProtKB:Q6QWF9}. Cell
CC projection, dendrite {ECO:0000269|PubMed:11182241}. Postsynaptic
CC density {ECO:0000250|UniProtKB:Q6QWF9}.
CC -!- TISSUE SPECIFICITY: Brain specific (PubMed:11182241). Highly expressed
CC in frontal cortex, hippocampus, olfactory bulb, caudate-putamen and
CC cerebellum (at protein level) (PubMed:11182241).
CC {ECO:0000269|PubMed:11182241}.
CC -!- DISRUPTION PHENOTYPE: Knockout in a spontaneously hypertensive rat
CC model results in decreased blood pressure and vascular reactivity to N-
CC omega-Nitro-L-arginine methyl ester hydrochloride (PubMed:31327268).
CC Increased renal and serum endothelial nitric oxide synthase and serum
CC nitrate levels (PubMed:31327268). Reduced fasting plasma glucose
CC concentrations and a 23% decrease in visceral and brown adipose tissue
CC relative mass, resulting from a decrease in adipocyte number
CC (PubMed:31327268). {ECO:0000269|PubMed:31327268}.
CC -!- SIMILARITY: Belongs to the CAMK2N family. {ECO:0000305}.
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DR EMBL; AF271156; AAF75281.1; -; mRNA.
DR RefSeq; NP_775459.1; NM_173337.1.
DR PDB; 3KL8; X-ray; 3.37 A; B/D/F/H/J=42-58.
DR PDBsum; 3KL8; -.
DR AlphaFoldDB; Q9JI15; -.
DR SMR; Q9JI15; -.
DR BioGRID; 251978; 1.
DR DIP; DIP-58987N; -.
DR IntAct; Q9JI15; 1.
DR STRING; 10116.ENSRNOP00000021864; -.
DR PaxDb; Q9JI15; -.
DR PRIDE; Q9JI15; -.
DR GeneID; 287005; -.
DR KEGG; rno:287005; -.
DR UCSC; RGD:708430; rat.
DR CTD; 55450; -.
DR RGD; 708430; Camk2n1.
DR eggNOG; ENOG502S6QW; Eukaryota.
DR HOGENOM; CLU_197183_0_0_1; -.
DR InParanoid; Q9JI15; -.
DR OMA; NEQKNGT; -.
DR OrthoDB; 1637105at2759; -.
DR PhylomeDB; Q9JI15; -.
DR TreeFam; TF333175; -.
DR EvolutionaryTrace; Q9JI15; -.
DR PRO; PR:Q9JI15; -.
DR Proteomes; UP000002494; Chromosome 5.
DR Bgee; ENSRNOG00000016322; Expressed in frontal cortex and 19 other tissues.
DR Genevisible; Q9JI15; RN.
DR GO; GO:0070161; C:anchoring junction; IEA:UniProtKB-KW.
DR GO; GO:0030425; C:dendrite; IDA:HGNC-UCL.
DR GO; GO:0043025; C:neuronal cell body; IDA:HGNC-UCL.
DR GO; GO:0014069; C:postsynaptic density; ISO:RGD.
DR GO; GO:0045202; C:synapse; ISS:UniProtKB.
DR GO; GO:0008427; F:calcium-dependent protein kinase inhibitor activity; IDA:HGNC-UCL.
DR GO; GO:0019901; F:protein kinase binding; IDA:HGNC-UCL.
DR GO; GO:0004860; F:protein kinase inhibitor activity; ISO:RGD.
DR GO; GO:0055074; P:calcium ion homeostasis; IMP:RGD.
DR GO; GO:0007268; P:chemical synaptic transmission; IC:HGNC-UCL.
DR GO; GO:0007616; P:long-term memory; ISS: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; ISS:UniProtKB.
DR GO; GO:0035774; P:positive regulation of insulin secretion involved in cellular response to glucose stimulus; IMP:RGD.
DR GO; GO:0003084; P:positive regulation of systemic arterial blood pressure; IMP:RGD.
DR InterPro; IPR026779; Camk2n.
DR PANTHER; PTHR31007; PTHR31007; 1.
DR Pfam; PF15170; CaM-KIIN; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Cell projection; Protein kinase inhibitor;
KW Reference proteome; Synapse.
FT CHAIN 1..78
FT /note="Calcium/calmodulin-dependent protein kinase II
FT inhibitor 1"
FT /id="PRO_0000338395"
FT REGION 41..68
FT /note="CAMK2 inhibitory domain"
FT MUTAGEN 43
FT /note="R->P: Reduces at least 100-fold the inhibitory
FT potency; when associated with 59-K--A-61."
FT /evidence="ECO:0000269|PubMed:11182241"
FT MUTAGEN 58
FT /note="I->S: Slightly phosphorylated."
FT /evidence="ECO:0000269|PubMed:11182241"
FT MUTAGEN 59..61
FT /note="EDD->KLA: Reduces at least 100-fold the inhibitory
FT potency; when associated with P-43."
FT /evidence="ECO:0000269|PubMed:11182241"
FT HELIX 47..50
FT /evidence="ECO:0007829|PDB:3KL8"
SQ SEQUENCE 78 AA; 8513 MW; A89A9E5DA11B8E61 CRC64;
MSEVLPYGDE KLSPYGDGGD VGQIFSCRLQ DTNNFFGAGQ SKRPPKLGQI GRSKRVVIED
DRIDDVLKTM TDKAPPGV
