KCC2D_MOUSE
ID KCC2D_MOUSE Reviewed; 499 AA.
AC Q6PHZ2; Q3UF87; Q3UQH9; Q5DTK4; Q8CAC5; Q9CZE2;
DT 20-FEB-2007, integrated into UniProtKB/Swiss-Prot.
DT 05-JUL-2004, sequence version 1.
DT 03-AUG-2022, entry version 169.
DE RecName: Full=Calcium/calmodulin-dependent protein kinase type II subunit delta;
DE Short=CaM kinase II subunit delta;
DE Short=CaMK-II subunit delta;
DE EC=2.7.11.17;
GN Name=Camk2d; Synonyms=Kiaa4163;
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 [LARGE SCALE MRNA] (ISOFORMS 2; 3 AND 4).
RC STRAIN=C57BL/6J; TISSUE=Hypothalamus, Stomach, and Sympathetic ganglion;
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 [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 4).
RC TISSUE=Fetal brain;
RA Okazaki N., Kikuno R.F., Ohara R., Inamoto S., Nagase T., Ohara O.,
RA Koga H.;
RT "Prediction of the coding sequences of mouse homologues of KIAA gene. The
RT complete nucleotide sequences of mouse KIAA-homologous cDNAs identified by
RT screening of terminal sequences of cDNA clones randomly sampled from size-
RT fractionated libraries.";
RL Submitted (FEB-2005) to the EMBL/GenBank/DDBJ databases.
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC STRAIN=C3H/He; TISSUE=Osteoblast;
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 [4]
RP TISSUE SPECIFICITY.
RX PubMed=10967556;
RX DOI=10.1002/1097-4644(20001101)79:2<293::aid-jcb120>3.0.co;2-q;
RA Hoch B., Wobus A.M., Krause E.G., Karczewski P.;
RT "delta-Ca(2+)/calmodulin-dependent protein kinase II expression pattern in
RT adult mouse heart and cardiogenic differentiation of embryonic stem
RT cells.";
RL J. Cell. Biochem. 79:293-300(2000).
RN [5]
RP FUNCTION IN CARDIAC HYPERTROPHY.
RX PubMed=12676814; DOI=10.1161/01.res.0000069686.31472.c5;
RA Zhang T., Maier L.S., Dalton N.D., Miyamoto S., Ross J. Jr., Bers D.M.,
RA Brown J.H.;
RT "The deltaC isoform of CaMKII is activated in cardiac hypertrophy and
RT induces dilated cardiomyopathy and heart failure.";
RL Circ. Res. 92:912-919(2003).
RN [6]
RP FUNCTION IN PHOSPHORYLATION OF POTASSIUM CHANNEL.
RX PubMed=15456698; DOI=10.1152/ajpcell.00293.2004;
RA Sergeant G.P., Ohya S., Reihill J.A., Perrino B.A., Amberg G.C.,
RA Imaizumi Y., Horowitz B., Sanders K.M., Koh S.D.;
RT "Regulation of Kv4.3 currents by Ca2+/calmodulin-dependent protein kinase
RT II.";
RL Am. J. Physiol. 288:C304-C313(2005).
RN [7]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Liver;
RX PubMed=17242355; DOI=10.1073/pnas.0609836104;
RA Villen J., Beausoleil S.A., Gerber S.A., Gygi S.P.;
RT "Large-scale phosphorylation analysis of mouse liver.";
RL Proc. Natl. Acad. Sci. U.S.A. 104:1488-1493(2007).
RN [8]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-330 AND THR-337, AND
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Embryonic fibroblast;
RX PubMed=19131326; DOI=10.1074/mcp.m800451-mcp200;
RA Sweet S.M., Bailey C.M., Cunningham D.L., Heath J.K., Cooper H.J.;
RT "Large scale localization of protein phosphorylation by use of electron
RT capture dissociation mass spectrometry.";
RL Mol. Cell. Proteomics 8:904-912(2009).
RN [9]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-333; THR-336; THR-337 AND
RP SER-494, AND IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Brain, Brown adipose tissue, Heart, Kidney, Liver, Lung, Spleen, and
RC Testis;
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 [10]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT LYS-318, AND IDENTIFICATION BY MASS
RP SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Embryonic fibroblast;
RX PubMed=23806337; DOI=10.1016/j.molcel.2013.06.001;
RA Park J., Chen Y., Tishkoff D.X., Peng C., Tan M., Dai L., Xie Z., Zhang Y.,
RA Zwaans B.M., Skinner M.E., Lombard D.B., Zhao Y.;
RT "SIRT5-mediated lysine desuccinylation impacts diverse metabolic
RT pathways.";
RL Mol. Cell 50:919-930(2013).
RN [11]
RP FUNCTION IN MYOCARDIAL REMODELING.
RX PubMed=15793582; DOI=10.1038/nm1215;
RA Zhang R., Khoo M.S., Wu Y., Yang Y., Grueter C.E., Ni G., Price E.E. Jr.,
RA Thiel W., Guatimosim S., Song L.S., Madu E.C., Shah A.N.,
RA Vishnivetskaya T.A., Atkinson J.B., Gurevich V.V., Salama G., Lederer W.J.,
RA Colbran R.J., Anderson M.E.;
RT "Calmodulin kinase II inhibition protects against structural heart
RT disease.";
RL Nat. Med. 11:409-417(2005).
RN [12]
RP FUNCTION IN PHOSPHORYLATION OF SODIUM CHANNEL.
RX PubMed=17124532; DOI=10.1172/jci26620;
RA Wagner S., Dybkova N., Rasenack E.C., Jacobshagen C., Fabritz L.,
RA Kirchhof P., Maier S.K., Zhang T., Hasenfuss G., Brown J.H., Bers D.M.,
RA Maier L.S.;
RT "Ca2+/calmodulin-dependent protein kinase II regulates cardiac Na+
RT channels.";
RL J. Clin. Invest. 116:3127-3138(2006).
RN [13]
RP FUNCTION IN CARDIAC HYPERTROPHIC CARDIOMYOPATHY.
RX PubMed=19381018; DOI=10.1172/jci38022;
RA Ling H., Zhang T., Pereira L., Means C.K., Cheng H., Gu Y., Dalton N.D.,
RA Peterson K.L., Chen J., Bers D., Heller Brown J.;
RT "Requirement for Ca2+/calmodulin-dependent kinase II in the transition from
RT pressure overload-induced cardiac hypertrophy to heart failure in mice.";
RL J. Clin. Invest. 119:1230-1240(2009).
RN [14]
RP FUNCTION IN CARDIAC HYPERTROPHY AND REMODELING.
RX PubMed=19179290; DOI=10.1073/pnas.0813013106;
RA Backs J., Backs T., Neef S., Kreusser M.M., Lehmann L.H., Patrick D.M.,
RA Grueter C.E., Qi X., Richardson J.A., Hill J.A., Katus H.A.,
RA Bassel-Duby R., Maier L.S., Olson E.N.;
RT "The delta isoform of CaM kinase II is required for pathological cardiac
RT hypertrophy and remodeling after pressure overload.";
RL Proc. Natl. Acad. Sci. U.S.A. 106:2342-2347(2009).
RN [15]
RP FUNCTION IN PHOSPHORYLATION OF L-TYPE CALCIUM CHANNEL, AND INTERACTION WITH
RP CACNB2.
RX PubMed=20194790; DOI=10.1073/pnas.0913760107;
RA Koval O.M., Guan X., Wu Y., Joiner M.L., Gao Z., Chen B., Grumbach I.M.,
RA Luczak E.D., Colbran R.J., Song L.S., Hund T.J., Mohler P.J.,
RA Anderson M.E.;
RT "CaV1.2 beta-subunit coordinates CaMKII-triggered cardiomyocyte death and
RT afterdepolarizations.";
RL Proc. Natl. Acad. Sci. U.S.A. 107:4996-5000(2010).
CC -!- FUNCTION: Calcium/calmodulin-dependent protein kinase involved in the
CC regulation of Ca(2+) homeostatis and excitation-contraction coupling
CC (ECC) in heart by targeting ion channels, transporters and accessory
CC proteins involved in Ca(2+) influx into the myocyte, Ca(2+) release
CC from the sarcoplasmic reticulum (SR), SR Ca(2+) uptake and Na(+) and
CC K(+) channel transport. Targets also transcription factors and
CC signaling molecules to regulate heart function. In its activated form,
CC is involved in the pathogenesis of dilated cardiomyopathy and heart
CC failure. Contributes to cardiac decompensation and heart failure by
CC regulating SR Ca(2+) release via direct phosphorylation of RYR2 Ca(2+)
CC channel on 'Ser-2808'. In the nucleus, phosphorylates the MEF2
CC repressor HDAC4, promoting its nuclear export and binding to 14-3-3
CC protein, and expression of MEF2 and genes involved in the hypertrophic
CC program. Is essential for left ventricular remodeling responses to
CC myocardial infarction. In pathological myocardial remodeling acts
CC downstream of the beta adrenergic receptor signaling cascade to
CC regulate key proteins involved in ECC. Regulates Ca(2+) influx to
CC myocytes by binding and phosphorylating the L-type Ca(2+) channel
CC subunit beta-2 CACNB2. In addition to Ca(2+) channels, can target and
CC regulate the cardiac sarcolemmal Na(+) channel Nav1.5/SCN5A and the K+
CC channel Kv4.3/KCND3, which contribute to arrhythmogenesis in heart
CC failure. Phosphorylates phospholamban (PLN/PLB), an endogenous
CC inhibitor of SERCA2A/ATP2A2, contributing to the enhancement of SR
CC Ca(2+) uptake that may be important in frequency-dependent acceleration
CC of relaxation (FDAR) and maintenance of contractile function during
CC acidosis. May participate in the modulation of skeletal muscle function
CC in response to exercise, by regulating SR Ca(2+) transport through
CC phosphorylation of PLN/PLB and triadin, a ryanodine receptor-coupling
CC factor. {ECO:0000269|PubMed:12676814, ECO:0000269|PubMed:15456698,
CC ECO:0000269|PubMed:15793582, ECO:0000269|PubMed:17124532,
CC ECO:0000269|PubMed:19179290, ECO:0000269|PubMed:19381018,
CC ECO:0000269|PubMed:20194790}.
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 -!- 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;
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-287 which turns
CC the kinase in a constitutively active form and confers to the kinase a
CC Ca(2+)-independent activity.
CC -!- SUBUNIT: CAMK2 is composed of 4 different chains: alpha (CAMK2A), beta
CC (CAMK2B), gamma (CAMK2G), and delta (CAMK2D). The different isoforms
CC assemble into homo- or heteromultimeric holoenzymes composed of 12
CC subunits with two hexameric rings stacked one on top of the other.
CC Interacts with RRAD (By similarity). Interacts with CACNB2.
CC {ECO:0000250, ECO:0000269|PubMed:20194790}.
CC -!- INTERACTION:
CC Q6PHZ2; Q9JJ28: Flii; NbExp=5; IntAct=EBI-2308458, EBI-7996161;
CC Q6PHZ2; E9Q401: Ryr2; NbExp=2; IntAct=EBI-2308458, EBI-643628;
CC -!- SUBCELLULAR LOCATION: Cell membrane, sarcolemma {ECO:0000305};
CC Peripheral membrane protein {ECO:0000305}; Cytoplasmic side
CC {ECO:0000305}. Sarcoplasmic reticulum membrane {ECO:0000305};
CC Peripheral membrane protein {ECO:0000305}; Cytoplasmic side
CC {ECO:0000305}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=4;
CC Name=1; Synonyms=Delta 2;
CC IsoId=Q6PHZ2-1; Sequence=Displayed;
CC Name=2; Synonyms=Delta 6;
CC IsoId=Q6PHZ2-2; Sequence=VSP_023103, VSP_023102;
CC Name=3; Synonyms=Delta 10;
CC IsoId=Q6PHZ2-4; Sequence=VSP_023101, VSP_023103, VSP_023102;
CC Name=4; Synonyms=Delta 5;
CC IsoId=Q6PHZ2-5; Sequence=VSP_023100, VSP_023103, VSP_023102;
CC -!- TISSUE SPECIFICITY: Expressed in cardiac muscle and skeletal muscle.
CC Isoform Delta 2, isoform Delta 6, isoform Delta 6 and isoform Delta 10
CC are expressed in cardiac muscle. Isoform Delta 2 is expressed in
CC skeletal muscle. {ECO:0000269|PubMed:10967556}.
CC -!- DOMAIN: The CAMK2 protein kinases contain a unique C-terminal subunit
CC association domain responsible for oligomerization.
CC -!- PTM: Autophosphorylation of Thr-287 following activation by
CC Ca(2+)/calmodulin. Phosphorylation of Thr-287 locks the kinase into an
CC activated state (By similarity). {ECO:0000250}.
CC -!- MISCELLANEOUS: Mice overexpressing CaMK2D develop a dilated
CC cardiomyopathy, enlarged myocytes with reduced contractility and
CC altered Ca(2+) handling, and die prematurely in PubMed:12676814.
CC -!- SIMILARITY: Belongs to the protein kinase superfamily. CAMK Ser/Thr
CC protein kinase family. CaMK subfamily. {ECO:0000305}.
CC -!- SEQUENCE CAUTION:
CC Sequence=BAD90304.1; Type=Erroneous initiation; Note=Extended N-terminus.; Evidence={ECO:0000305};
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DR EMBL; AK039076; BAC30232.1; -; mRNA.
DR EMBL; AK012702; BAB28422.1; -; mRNA.
DR EMBL; AK142435; BAE25062.1; -; mRNA.
DR EMBL; AK148840; BAE28674.1; -; mRNA.
DR EMBL; AK220516; BAD90304.1; ALT_INIT; mRNA.
DR EMBL; BC052894; AAH52894.1; -; mRNA.
DR CCDS; CCDS17823.1; -. [Q6PHZ2-1]
DR CCDS; CCDS51065.1; -. [Q6PHZ2-2]
DR CCDS; CCDS80015.1; -. [Q6PHZ2-5]
DR CCDS; CCDS80016.1; -. [Q6PHZ2-4]
DR RefSeq; NP_001020609.1; NM_001025438.2. [Q6PHZ2-1]
DR RefSeq; NP_001020610.1; NM_001025439.2.
DR RefSeq; NP_001280592.1; NM_001293663.1. [Q6PHZ2-5]
DR RefSeq; NP_001280593.1; NM_001293664.1. [Q6PHZ2-4]
DR RefSeq; NP_076302.1; NM_023813.4. [Q6PHZ2-2]
DR PDB; 6BAB; X-ray; 1.91 A; A/B/C/D=3-301.
DR PDBsum; 6BAB; -.
DR AlphaFoldDB; Q6PHZ2; -.
DR SMR; Q6PHZ2; -.
DR BioGRID; 223798; 22.
DR DIP; DIP-47638N; -.
DR IntAct; Q6PHZ2; 26.
DR MINT; Q6PHZ2; -.
DR STRING; 10090.ENSMUSP00000102009; -.
DR iPTMnet; Q6PHZ2; -.
DR MetOSite; Q6PHZ2; -.
DR PhosphoSitePlus; Q6PHZ2; -.
DR SwissPalm; Q6PHZ2; -.
DR EPD; Q6PHZ2; -.
DR jPOST; Q6PHZ2; -.
DR MaxQB; Q6PHZ2; -.
DR PeptideAtlas; Q6PHZ2; -.
DR PRIDE; Q6PHZ2; -.
DR ProteomicsDB; 269245; -. [Q6PHZ2-1]
DR ProteomicsDB; 269246; -. [Q6PHZ2-2]
DR ProteomicsDB; 269247; -. [Q6PHZ2-4]
DR ProteomicsDB; 269248; -. [Q6PHZ2-5]
DR DNASU; 108058; -.
DR Ensembl; ENSMUST00000066466; ENSMUSP00000063359; ENSMUSG00000053819. [Q6PHZ2-4]
DR Ensembl; ENSMUST00000106400; ENSMUSP00000102008; ENSMUSG00000053819. [Q6PHZ2-2]
DR Ensembl; ENSMUST00000106402; ENSMUSP00000102010; ENSMUSG00000053819. [Q6PHZ2-5]
DR Ensembl; ENSMUST00000199300; ENSMUSP00000143504; ENSMUSG00000053819. [Q6PHZ2-1]
DR GeneID; 108058; -.
DR KEGG; mmu:108058; -.
DR UCSC; uc008rgh.2; mouse. [Q6PHZ2-1]
DR UCSC; uc008rgl.2; mouse. [Q6PHZ2-2]
DR UCSC; uc008rgn.2; mouse. [Q6PHZ2-5]
DR UCSC; uc008rgo.2; mouse. [Q6PHZ2-4]
DR CTD; 817; -.
DR MGI; MGI:1341265; Camk2d.
DR VEuPathDB; HostDB:ENSMUSG00000053819; -.
DR eggNOG; KOG0033; Eukaryota.
DR GeneTree; ENSGT00940000159769; -.
DR InParanoid; Q6PHZ2; -.
DR PhylomeDB; Q6PHZ2; -.
DR BRENDA; 2.7.11.17; 3474.
DR Reactome; R-MMU-3371571; HSF1-dependent transactivation.
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; 108058; 1 hit in 75 CRISPR screens.
DR ChiTaRS; Camk2d; mouse.
DR PRO; PR:Q6PHZ2; -.
DR Proteomes; UP000000589; Chromosome 3.
DR RNAct; Q6PHZ2; protein.
DR Bgee; ENSMUSG00000053819; Expressed in anterior amygdaloid area and 249 other tissues.
DR ExpressionAtlas; Q6PHZ2; baseline and differential.
DR Genevisible; Q6PHZ2; MM.
DR GO; GO:0043194; C:axon initial segment; IDA:MGI.
DR GO; GO:0005954; C:calcium- and calmodulin-dependent protein kinase complex; ISO:MGI.
DR GO; GO:0005737; C:cytoplasm; IDA:MGI.
DR GO; GO:0005829; C:cytosol; ISO:MGI.
DR GO; GO:0014704; C:intercalated disc; IDA:MGI.
DR GO; GO:0031594; C:neuromuscular junction; IDA:MGI.
DR GO; GO:0043005; C:neuron projection; IBA:GO_Central.
DR GO; GO:0043025; C:neuronal cell body; IDA:MGI.
DR GO; GO:0005634; C:nucleus; IDA:MGI.
DR GO; GO:0048471; C:perinuclear region of cytoplasm; ISO:MGI.
DR GO; GO:0032991; C:protein-containing complex; ISO:MGI.
DR GO; GO:0033017; C:sarcoplasmic reticulum membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0030315; C:T-tubule; IDA:MGI.
DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
DR GO; GO:0005516; F:calmodulin binding; ISO:MGI.
DR GO; GO:0004683; F:calmodulin-dependent protein kinase activity; ISS:BHF-UCL.
DR GO; GO:0042802; F:identical protein binding; ISO:MGI.
DR GO; GO:0050998; F:nitric-oxide synthase binding; ISO:MGI.
DR GO; GO:0042803; F:protein homodimerization activity; ISO:MGI.
DR GO; GO:0004672; F:protein kinase 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:0019871; F:sodium channel inhibitor activity; ISO:MGI.
DR GO; GO:0031432; F:titin binding; ISO:MGI.
DR GO; GO:0044325; F:transmembrane transporter binding; IPI:BHF-UCL.
DR GO; GO:0006816; P:calcium ion transport; IDA:MGI.
DR GO; GO:0086003; P:cardiac muscle cell contraction; ISS:BHF-UCL.
DR GO; GO:0060048; P:cardiac muscle contraction; IDA:MGI.
DR GO; GO:0061049; P:cell growth involved in cardiac muscle cell development; ISO:MGI.
DR GO; GO:0030007; P:cellular potassium ion homeostasis; ISO:MGI.
DR GO; GO:0032469; P:endoplasmic reticulum calcium ion homeostasis; ISO:MGI.
DR GO; GO:0000082; P:G1/S transition of mitotic cell cycle; IMP:MGI.
DR GO; GO:1902306; P:negative regulation of sodium ion transmembrane transport; ISO:MGI.
DR GO; GO:2000650; P:negative regulation of sodium ion transmembrane transporter activity; ISO:MGI.
DR GO; GO:0018105; P:peptidyl-serine phosphorylation; IDA:MGI.
DR GO; GO:0018107; P:peptidyl-threonine phosphorylation; ISS:BHF-UCL.
DR GO; GO:0010666; P:positive regulation of cardiac muscle cell apoptotic process; ISO:MGI.
DR GO; GO:0010613; P:positive regulation of cardiac muscle hypertrophy; ISS:UniProtKB.
DR GO; GO:2000573; P:positive regulation of DNA biosynthetic process; ISO:MGI.
DR GO; GO:0070374; P:positive regulation of ERK1 and ERK2 cascade; ISO:MGI.
DR GO; GO:0010971; P:positive regulation of G2/M transition of mitotic cell cycle; ISO:MGI.
DR GO; GO:0035022; P:positive regulation of Rac protein signal transduction; ISO:MGI.
DR GO; GO:0014911; P:positive regulation of smooth muscle cell migration; ISO:MGI.
DR GO; GO:1904707; P:positive regulation of vascular associated smooth muscle cell proliferation; ISO:MGI.
DR GO; GO:0046777; P:protein autophosphorylation; IMP:MGI.
DR GO; GO:0006468; P:protein phosphorylation; ISS:UniProtKB.
DR GO; GO:1902514; P:regulation of calcium ion transmembrane transport via high voltage-gated calcium channel; ISO:MGI.
DR GO; GO:0098901; P:regulation of cardiac muscle cell action potential; ISO:MGI.
DR GO; GO:0010649; P:regulation of cell communication by electrical coupling; ISO:MGI.
DR GO; GO:0060341; P:regulation of cellular localization; ISS:UniProtKB.
DR GO; GO:0003254; P:regulation of membrane depolarization; ISO:MGI.
DR GO; GO:1903076; P:regulation of protein localization to plasma membrane; ISO:MGI.
DR GO; GO:1901897; P:regulation of relaxation of cardiac muscle; IGI:BHF-UCL.
DR GO; GO:0010880; P:regulation of release of sequestered calcium ion into cytosol by sarcoplasmic reticulum; ISO:MGI.
DR GO; GO:0002028; P:regulation of sodium ion transport; IDA:MGI.
DR GO; GO:0055119; P:relaxation of cardiac muscle; ISS:BHF-UCL.
DR GO; GO:0001666; P:response to hypoxia; ISO: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; Acetylation; Alternative splicing; ATP-binding;
KW Calmodulin-binding; Cell membrane; Kinase; Membrane; Nucleotide-binding;
KW Phosphoprotein; Reference proteome; Sarcoplasmic reticulum;
KW Serine/threonine-protein kinase; Transferase.
FT INIT_MET 1
FT /note="Removed"
FT /evidence="ECO:0000250|UniProtKB:Q13557"
FT CHAIN 2..499
FT /note="Calcium/calmodulin-dependent protein kinase type II
FT subunit delta"
FT /id="PRO_0000277817"
FT DOMAIN 14..272
FT /note="Protein kinase"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT REGION 283..292
FT /note="Autoinhibitory domain"
FT /evidence="ECO:0000250"
FT REGION 291..301
FT /note="Calmodulin-binding"
FT /evidence="ECO:0000250"
FT ACT_SITE 136
FT /note="Proton acceptor"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159,
FT ECO:0000255|PROSITE-ProRule:PRU10027"
FT BINDING 20..28
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT BINDING 43
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT MOD_RES 2
FT /note="N-acetylalanine"
FT /evidence="ECO:0000250|UniProtKB:Q13557"
FT MOD_RES 287
FT /note="Phosphothreonine; by autocatalysis"
FT /evidence="ECO:0000250|UniProtKB:Q13557, ECO:0000305"
FT MOD_RES 306
FT /note="Phosphothreonine; by autocatalysis"
FT /evidence="ECO:0000250"
FT MOD_RES 307
FT /note="Phosphothreonine; by autocatalysis"
FT /evidence="ECO:0000250"
FT MOD_RES 315
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q13557"
FT MOD_RES 318
FT /note="N6-acetyllysine"
FT /evidence="ECO:0007744|PubMed:23806337"
FT MOD_RES 319
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q13557"
FT MOD_RES 330
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:19131326"
FT MOD_RES 331
FT /note="Phosphothreonine"
FT /evidence="ECO:0000250|UniProtKB:Q13557"
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:19131326,
FT ECO:0007744|PubMed:21183079"
FT MOD_RES 404
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q13557"
FT MOD_RES 490
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q13557"
FT MOD_RES 494
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:21183079"
FT VAR_SEQ 328
FT /note="K -> KINNKANVVTSPKENIPTPALEPQTTVIHNPDGNK (in isoform
FT 4)"
FT /evidence="ECO:0000303|PubMed:16141072, ECO:0000303|Ref.2"
FT /id="VSP_023100"
FT VAR_SEQ 329
FT /note="E -> EPQTTVIHNPDGNKE (in isoform 3)"
FT /evidence="ECO:0000303|PubMed:16141072"
FT /id="VSP_023101"
FT VAR_SEQ 478
FT /note="K -> N (in isoform 2, isoform 3 and isoform 4)"
FT /evidence="ECO:0000303|PubMed:16141072, ECO:0000303|Ref.2"
FT /id="VSP_023103"
FT VAR_SEQ 479..499
FT /note="Missing (in isoform 2, isoform 3 and isoform 4)"
FT /evidence="ECO:0000303|PubMed:16141072, ECO:0000303|Ref.2"
FT /id="VSP_023102"
FT CONFLICT 123..125
FT /note="SVN -> AVL (in Ref. 1; BAC30232)"
FT /evidence="ECO:0000305"
FT CONFLICT 129..132
FT /note="LNGI -> QMGV (in Ref. 1; BAC30232)"
FT /evidence="ECO:0000305"
FT CONFLICT 199
FT /note="A -> V (in Ref. 1; BAC30232)"
FT /evidence="ECO:0000305"
FT STRAND 13..23
FT /evidence="ECO:0007829|PDB:6BAB"
FT STRAND 26..33
FT /evidence="ECO:0007829|PDB:6BAB"
FT TURN 34..37
FT /evidence="ECO:0007829|PDB:6BAB"
FT STRAND 38..46
FT /evidence="ECO:0007829|PDB:6BAB"
FT HELIX 54..67
FT /evidence="ECO:0007829|PDB:6BAB"
FT STRAND 76..81
FT /evidence="ECO:0007829|PDB:6BAB"
FT STRAND 83..91
FT /evidence="ECO:0007829|PDB:6BAB"
FT HELIX 98..102
FT /evidence="ECO:0007829|PDB:6BAB"
FT HELIX 110..129
FT /evidence="ECO:0007829|PDB:6BAB"
FT HELIX 139..141
FT /evidence="ECO:0007829|PDB:6BAB"
FT STRAND 142..144
FT /evidence="ECO:0007829|PDB:6BAB"
FT HELIX 147..149
FT /evidence="ECO:0007829|PDB:6BAB"
FT STRAND 153..155
FT /evidence="ECO:0007829|PDB:6BAB"
FT HELIX 178..180
FT /evidence="ECO:0007829|PDB:6BAB"
FT HELIX 183..186
FT /evidence="ECO:0007829|PDB:6BAB"
FT HELIX 194..209
FT /evidence="ECO:0007829|PDB:6BAB"
FT HELIX 219..228
FT /evidence="ECO:0007829|PDB:6BAB"
FT HELIX 237..240
FT /evidence="ECO:0007829|PDB:6BAB"
FT HELIX 243..252
FT /evidence="ECO:0007829|PDB:6BAB"
FT TURN 257..259
FT /evidence="ECO:0007829|PDB:6BAB"
FT HELIX 263..266
FT /evidence="ECO:0007829|PDB:6BAB"
FT HELIX 270..273
FT /evidence="ECO:0007829|PDB:6BAB"
FT HELIX 275..278
FT /evidence="ECO:0007829|PDB:6BAB"
FT HELIX 285..299
FT /evidence="ECO:0007829|PDB:6BAB"
FT CONFLICT Q6PHZ2-2:478
FT /note="N -> K (in Ref. 1; BAE25062)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 499 AA; 56369 MW; 62999FBAB98120CE CRC64;
MASTTTCTRF TDEYQLFEEL GKGAFSVVRR CMKIPTGQEY AAKIINTKKL SARDHQKLER
EARICRLLKH PNIVRLHDSI SEEGFHYLVF DLVTGGELFE DIVAREYYSE ADASHCIQQI
LESVNHCHLN GIVHRDLKPE NLLLASKSKG AAVKLADFGL AIEVQGDQQA WFGFAGTPGY
LSPEVLRKDP YGKPVDMWAC GVILYILLVG YPPFWDEDQH RLYQQIKAGA YDFPSPEWDT
VTPEAKDLIN KMLTINPAKR ITASEALKHP WICQRSTVAS MMHRQETVDC LKKFNARRKL
KGAILTTMLA TRNFSAAKSL LKKPDGVKES TESSNTTIED EDVKARKQEI IKVTEQLIEA
INNGDFEAYT KICDPGLTAF EPEALGNLVE GMDFHRFYFE NALSKSNKPI HTIILNPHVH
LVGDDAACIA YIRLTQYMDG SGMPKTMQSE ETRVWHRRDG KWQNVHFHRS GSPTVPIKPP
CIPNGKENFS GGTSLWQNI
