Full text data of CAMK2G
CAMK2G
(CAMK, CAMK-II, CAMKG)
[Confidence: low (only semi-automatic identification from reviews)]
Calcium/calmodulin-dependent protein kinase type II subunit gamma; CaM kinase II subunit gamma; CaMK-II subunit gamma; 2.7.11.17
Calcium/calmodulin-dependent protein kinase type II subunit gamma; CaM kinase II subunit gamma; CaMK-II subunit gamma; 2.7.11.17
UniProt
Q13555
ID KCC2G_HUMAN Reviewed; 558 AA.
AC Q13555; O00561; O15378; Q13279; Q13282; Q13556; Q5SQZ3; Q5SQZ4;
read moreAC Q5SWX4; Q7KYX5; Q8N4I3; Q8NIA4;
DT 01-NOV-1997, integrated into UniProtKB/Swiss-Prot.
DT 12-APR-2005, sequence version 3.
DT 22-JAN-2014, entry version 140.
DE RecName: Full=Calcium/calmodulin-dependent protein kinase type II subunit gamma;
DE Short=CaM kinase II subunit gamma;
DE Short=CaMK-II subunit gamma;
DE EC=2.7.11.17;
GN Name=CAMK2G; Synonyms=CAMK, CAMK-II, CAMKG;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
OC Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini;
OC Catarrhini; Hominidae; Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=15164054; DOI=10.1038/nature02462;
RA Deloukas P., Earthrowl M.E., Grafham D.V., Rubenfield M., French L.,
RA Steward C.A., Sims S.K., Jones M.C., Searle S., Scott C., Howe K.,
RA Hunt S.E., Andrews T.D., Gilbert J.G.R., Swarbreck D., Ashurst J.L.,
RA Taylor A., Battles J., Bird C.P., Ainscough R., Almeida J.P.,
RA Ashwell R.I.S., Ambrose K.D., Babbage A.K., Bagguley C.L., Bailey J.,
RA Banerjee R., Bates K., Beasley H., Bray-Allen S., Brown A.J.,
RA Brown J.Y., Burford D.C., Burrill W., Burton J., Cahill P., Camire D.,
RA Carter N.P., Chapman J.C., Clark S.Y., Clarke G., Clee C.M., Clegg S.,
RA Corby N., Coulson A., Dhami P., Dutta I., Dunn M., Faulkner L.,
RA Frankish A., Frankland J.A., Garner P., Garnett J., Gribble S.,
RA Griffiths C., Grocock R., Gustafson E., Hammond S., Harley J.L.,
RA Hart E., Heath P.D., Ho T.P., Hopkins B., Horne J., Howden P.J.,
RA Huckle E., Hynds C., Johnson C., Johnson D., Kana A., Kay M.,
RA Kimberley A.M., Kershaw J.K., Kokkinaki M., Laird G.K., Lawlor S.,
RA Lee H.M., Leongamornlert D.A., Laird G., Lloyd C., Lloyd D.M.,
RA Loveland J., Lovell J., McLaren S., McLay K.E., McMurray A.,
RA Mashreghi-Mohammadi M., Matthews L., Milne S., Nickerson T.,
RA Nguyen M., Overton-Larty E., Palmer S.A., Pearce A.V., Peck A.I.,
RA Pelan S., Phillimore B., Porter K., Rice C.M., Rogosin A., Ross M.T.,
RA Sarafidou T., Sehra H.K., Shownkeen R., Skuce C.D., Smith M.,
RA Standring L., Sycamore N., Tester J., Thorpe A., Torcasso W.,
RA Tracey A., Tromans A., Tsolas J., Wall M., Walsh J., Wang H.,
RA Weinstock K., West A.P., Willey D.L., Whitehead S.L., Wilming L.,
RA Wray P.W., Young L., Chen Y., Lovering R.C., Moschonas N.K.,
RA Siebert R., Fechtel K., Bentley D., Durbin R.M., Hubbard T.,
RA Doucette-Stamm L., Beck S., Smith D.R., Rogers J.;
RT "The DNA sequence and comparative analysis of human chromosome 10.";
RL Nature 429:375-381(2004).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA], AND VARIANT PRO-36.
RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L.,
RA Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R.,
RA Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V.,
RA Hannenhalli S., Turner R., Yooseph S., Lu F., Nusskern D.R.,
RA Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H.,
RA Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G.,
RA Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W.,
RA Venter J.C.;
RL Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases.
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 5), AND VARIANT
RP PRO-36.
RC TISSUE=Brain;
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
RT project: the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [4]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 1-315.
RX PubMed=9240463; DOI=10.1006/bbrc.1997.6871;
RA Breen M.A., Ashcroft S.J.;
RT "Human islets of Langerhans express multiple isoforms of
RT calcium/calmodulin-dependent protein kinase II.";
RL Biochem. Biophys. Res. Commun. 236:473-478(1997).
RN [5]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 23-558, AND ALTERNATIVE SPLICING
RP (ISOFORM 6).
RX PubMed=12032636; DOI=10.1007/s00125-002-0779-8;
RA Gloyn A.L., Desai M., Clark A., Levy J.C., Holman R.R., Frayling T.M.,
RA Hattersley A.T., Ashcroft S.J.;
RT "Human calcium/calmodulin-dependent protein kinase II gamma: cloning,
RT genomic structure and detection of variants in subjects with type II
RT diabetes.";
RL Diabetologia 45:580-583(2002).
RN [6]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 66-436 (ISOFORM 10).
RX PubMed=8449910;
RA Nghiem P., Saati S.M., Martens C.L., Gardner P., Schulman H.;
RT "Cloning and analysis of two new isoforms of multifunctional
RT Ca2+/calmodulin-dependent protein kinase. Expression in multiple human
RT tissues.";
RL J. Biol. Chem. 268:5471-5479(1993).
RN [7]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 302-497 (ISOFORMS 2 AND 4).
RX PubMed=9060999; DOI=10.1016/S0167-4889(96)00141-3;
RA Tombes R.M., Krystal G.W.;
RT "Identification of novel human tumor cell-specific CaMK-II variants.";
RL Biochim. Biophys. Acta 1355:281-292(1997).
RN [8]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 326-432 (ISOFORMS 7; 8 AND 9).
RX PubMed=7557101;
RA Kwiatkowski A.P., McGill J.M.;
RT "Human biliary epithelial cell line Mz-ChA-1 expresses new isoforms of
RT calmodulin-dependent protein kinase II.";
RL Gastroenterology 109:1316-1323(1995).
RN [9]
RP ENZYME REGULATION, SUBUNIT, AND AUTOPHOSPHORYLATION.
RX PubMed=14722083; DOI=10.1074/jbc.M313597200;
RA Gaertner T.R., Kolodziej S.J., Wang D., Kobayashi R., Koomen J.M.,
RA Stoops J.K., Waxham M.N.;
RT "Comparative analyses of the three-dimensional structures and
RT enzymatic properties of alpha, beta, gamma and delta isoforms of Ca2+-
RT calmodulin-dependent protein kinase II.";
RL J. Biol. Chem. 279:12484-12494(2004).
RN [10]
RP FUNCTION IN SKELETAL MUSCLE, PHOSPHORYLATION AT THR-287, FUNCTION IN
RP PHOSPHORYLATION OF PLN, TISSUE SPECIFICITY, AND INDUCTION.
RX PubMed=16690701; DOI=10.1113/jphysiol.2006.111757;
RA Rose A.J., Kiens B., Richter E.A.;
RT "Ca2+-calmodulin-dependent protein kinase expression and signalling in
RT skeletal muscle during exercise.";
RL J. Physiol. (Lond.) 574:889-903(2006).
RN [11]
RP REVIEW ON FUNCTION IN SKELETAL MUSCLE.
RX PubMed=15294044; DOI=10.1079/PNS2004335;
RA Chin E.R.;
RT "The role of calcium and calcium/calmodulin-dependent kinases in
RT skeletal muscle plasticity and mitochondrial biogenesis.";
RL Proc. Nutrit. Soc. 63:279-286(2004).
RN [12]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-311; SER-349; SER-352
RP AND SER-419, PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-325
RP (ISOFORMS 10; 2; 3; 5; 6; 7; 8 AND 9), PHOSPHORYLATION [LARGE SCALE
RP ANALYSIS] AT SER-338 (ISOFORM 9), AND MASS SPECTROMETRY.
RC TISSUE=Cervix carcinoma;
RX PubMed=18691976; DOI=10.1016/j.molcel.2008.07.007;
RA Daub H., Olsen J.V., Bairlein M., Gnad F., Oppermann F.S., Korner R.,
RA Greff Z., Keri G., Stemmann O., Mann M.;
RT "Kinase-selective enrichment enables quantitative phosphoproteomics of
RT the kinome across the cell cycle.";
RL Mol. Cell 31:438-448(2008).
RN [13]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=18669648; DOI=10.1073/pnas.0805139105;
RA Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E.,
RA Elledge S.J., Gygi S.P.;
RT "A quantitative atlas of mitotic phosphorylation.";
RL Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008).
RN [14]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-287; SER-311; SER-352
RP AND SER-419, PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-325
RP (ISOFORMS 10; 2; 3; 7; 8 AND 9), AND MASS SPECTROMETRY.
RX PubMed=19369195; DOI=10.1074/mcp.M800588-MCP200;
RA Oppermann F.S., Gnad F., Olsen J.V., Hornberger R., Greff Z., Keri G.,
RA Mann M., Daub H.;
RT "Large-scale proteomics analysis of the human kinome.";
RL Mol. Cell. Proteomics 8:1751-1764(2009).
RN [15]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-311, AND MASS
RP SPECTROMETRY.
RC TISSUE=Cervix carcinoma;
RX PubMed=20068231; DOI=10.1126/scisignal.2000475;
RA Olsen J.V., Vermeulen M., Santamaria A., Kumar C., Miller M.L.,
RA Jensen L.J., Gnad F., Cox J., Jensen T.S., Nigg E.A., Brunak S.,
RA Mann M.;
RT "Quantitative phosphoproteomics reveals widespread full
RT phosphorylation site occupancy during mitosis.";
RL Sci. Signal. 3:RA3-RA3(2010).
RN [16]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=21269460; DOI=10.1186/1752-0509-5-17;
RA Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P.,
RA Buerckstuemmer T., Bennett K.L., Superti-Furga G., Colinge J.;
RT "Initial characterization of the human central proteome.";
RL BMC Syst. Biol. 5:17-17(2011).
RN [17]
RP X-RAY CRYSTALLOGRAPHY (2.25 ANGSTROMS) OF 5-315 AND 426-556 IN COMPLEX
RP WITH INHIBITOR.
RX PubMed=20668654; DOI=10.1371/journal.pbio.1000426;
RA Rellos P., Pike A.C., Niesen F.H., Salah E., Lee W.H., von Delft F.,
RA Knapp S.;
RT "Structure of the CaMKIIdelta/calmodulin complex reveals the molecular
RT mechanism of CaMKII kinase activation.";
RL PLoS Biol. 8:E1000426-E1000426(2010).
RN [18]
RP VARIANT PRO-292.
RX PubMed=23033978; DOI=10.1056/NEJMoa1206524;
RA de Ligt J., Willemsen M.H., van Bon B.W., Kleefstra T., Yntema H.G.,
RA Kroes T., Vulto-van Silfhout A.T., Koolen D.A., de Vries P.,
RA Gilissen C., del Rosario M., Hoischen A., Scheffer H., de Vries B.B.,
RA Brunner H.G., Veltman J.A., Vissers L.E.;
RT "Diagnostic exome sequencing in persons with severe intellectual
RT disability.";
RL N. Engl. J. Med. 367:1921-1929(2012).
CC -!- FUNCTION: Calcium/calmodulin-dependent protein kinase that
CC functions autonomously after Ca(2+)/calmodulin-binding and
CC autophosphorylation, and is involved in sarcoplsamic reticulum
CC Ca(2+) transport in skeletal muscle and may function in dendritic
CC spine and synapse formation and neuronal plasticity. In slow-
CC twitch muscles, is involved in regulation of sarcoplasmic
CC reticulum (SR) Ca(2+) transport and in fast-twitch muscle
CC participates in the control of Ca(2+) release from the SR through
CC phosphorylation of the ryanodine receptor-coupling factor triadin.
CC In neurons, may participate in the promotion of dendritic spine
CC and synapse formation and maintenance of synaptic plasticity which
CC enables long-term potentiation (LTP) and hippocampus-dependent
CC learning.
CC -!- CATALYTIC ACTIVITY: ATP + a protein = ADP + a phosphoprotein.
CC -!- ENZYME REGULATION: Activated by Ca(2+)/calmodulin. Binding of
CC calmodulin results in conformational change that relieves
CC intrasteric autoinhibition and allows autophosphorylation of Thr-
CC 287 which turns the kinase in a constitutively active form and
CC confers to the kinase a Ca(2+)-independent activity.
CC -!- SUBUNIT: CAMK2 is composed of 4 different chains: alpha (CAMK2A),
CC beta (CAMK2B), gamma (CAMK2G), and delta (CAMK2D). The different
CC isoforms assemble into homo- or heteromultimeric holoenzymes
CC composed of 12 subunits with two hexameric rings stacked one on
CC top of the other.
CC -!- INTERACTION:
CC P08238:HSP90AB1; NbExp=2; IntAct=EBI-1383465, EBI-352572;
CC -!- SUBCELLULAR LOCATION: Sarcoplasmic reticulum membrane; Peripheral
CC membrane protein; Cytoplasmic side (Probable).
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=10;
CC Name=1;
CC IsoId=Q13555-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q13555-2; Sequence=VSP_013349;
CC Note=Contains a phosphoserine at position 325;
CC Name=3;
CC IsoId=Q13555-3; Sequence=VSP_013350;
CC Note=Contains a phosphoserine at position 325;
CC Name=4;
CC IsoId=Q13555-4; Sequence=VSP_004778;
CC Name=5;
CC IsoId=Q13555-5; Sequence=VSP_032699, VSP_032700, VSP_004778;
CC Note=Contains a phosphoserine at position 325;
CC Name=6;
CC IsoId=Q13555-6; Sequence=VSP_032699, VSP_035456;
CC Note=Contains a phosphoserine at position 325;
CC Name=7; Synonyms=gamma F;
CC IsoId=Q13555-7; Sequence=VSP_013350, VSP_035456;
CC Note=Contains a phosphoserine at position 325;
CC Name=8; Synonyms=gamma E;
CC IsoId=Q13555-8; Sequence=VSP_013349, VSP_035456;
CC Note=Contains a phosphoserine at position 325;
CC Name=9; Synonyms=gamma D;
CC IsoId=Q13555-9; Sequence=VSP_013349, VSP_036027, VSP_035456;
CC Note=Contains a phosphoserine at position 325. Contains a
CC phosphoserine at position 338;
CC Name=10;
CC IsoId=Q13555-10; Sequence=VSP_013350, VSP_004778;
CC Note=Contains a phosphoserine at position 325;
CC -!- TISSUE SPECIFICITY: Expressed in skeletal muscle.
CC -!- INDUCTION: Activity is induced in skeletal muscle during exercise.
CC -!- DOMAIN: The CAMK2 protein kinases contain a unique C-terminal
CC subunit 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
CC into an activated state.
CC -!- SIMILARITY: Belongs to the protein kinase superfamily. CAMK
CC Ser/Thr protein kinase family. CaMK subfamily.
CC -!- SIMILARITY: Contains 1 protein kinase domain.
CC -!- SEQUENCE CAUTION:
CC Sequence=AAB61379.1; Type=Erroneous initiation; Note=Translation N-terminally extended;
CC -----------------------------------------------------------------------
CC Copyrighted by the UniProt Consortium, see http://www.uniprot.org/terms
CC Distributed under the Creative Commons Attribution-NoDerivs License
CC -----------------------------------------------------------------------
DR EMBL; AL713896; CAI13789.1; -; Genomic_DNA.
DR EMBL; AC022400; CAI13789.1; JOINED; Genomic_DNA.
DR EMBL; AL596247; CAI13789.1; JOINED; Genomic_DNA.
DR EMBL; AL713896; CAI13790.1; -; Genomic_DNA.
DR EMBL; AC022400; CAI13790.1; JOINED; Genomic_DNA.
DR EMBL; AL596247; CAI13790.1; JOINED; Genomic_DNA.
DR EMBL; AL713896; CAI13791.1; -; Genomic_DNA.
DR EMBL; AC022400; CAI13791.1; JOINED; Genomic_DNA.
DR EMBL; AL596247; CAI13791.1; JOINED; Genomic_DNA.
DR EMBL; AL596247; CAI13965.1; -; Genomic_DNA.
DR EMBL; AC022400; CAI13965.1; JOINED; Genomic_DNA.
DR EMBL; AL713896; CAI13965.1; JOINED; Genomic_DNA.
DR EMBL; AL596247; CAI13966.1; -; Genomic_DNA.
DR EMBL; AC022400; CAI13966.1; JOINED; Genomic_DNA.
DR EMBL; AL713896; CAI13966.1; JOINED; Genomic_DNA.
DR EMBL; AL596247; CAI13968.1; -; Genomic_DNA.
DR EMBL; AC022400; CAI13968.1; JOINED; Genomic_DNA.
DR EMBL; AL713896; CAI13968.1; JOINED; Genomic_DNA.
DR EMBL; CH471083; EAW54532.1; -; Genomic_DNA.
DR EMBL; CH471083; EAW54536.1; -; Genomic_DNA.
DR EMBL; BC034044; AAH34044.1; -; mRNA.
DR EMBL; U66064; AAB80848.1; -; mRNA.
DR EMBL; AH011636; AAM33514.1; -; Genomic_DNA.
DR EMBL; L07043; AAB61379.1; ALT_INIT; mRNA.
DR EMBL; U50359; AAB16864.1; -; mRNA.
DR EMBL; U50360; AAB16865.1; -; mRNA.
DR EMBL; U32472; AAA75201.1; -; mRNA.
DR EMBL; U32473; AAA75202.1; -; mRNA.
DR EMBL; U32509; AAA75203.1; -; mRNA.
DR PIR; G01975; G01975.
DR PIR; G01978; G01978.
DR RefSeq; NP_001213.2; NM_001222.3.
DR RefSeq; NP_751909.1; NM_172169.2.
DR RefSeq; NP_751913.1; NM_172173.2.
DR RefSeq; XP_005270258.1; XM_005270201.1.
DR RefSeq; XP_005270259.1; XM_005270202.1.
DR RefSeq; XP_005270260.1; XM_005270203.1.
DR UniGene; Hs.523045; -.
DR PDB; 2UX0; X-ray; 2.46 A; A/B/C/D/E/F=426-556.
DR PDB; 2V7O; X-ray; 2.25 A; A=5-315.
DR PDBsum; 2UX0; -.
DR PDBsum; 2V7O; -.
DR ProteinModelPortal; Q13555; -.
DR SMR; Q13555; 3-302, 387-552.
DR DIP; DIP-51315N; -.
DR IntAct; Q13555; 3.
DR BindingDB; Q13555; -.
DR ChEMBL; CHEMBL2097164; -.
DR GuidetoPHARMACOLOGY; 1557; -.
DR PhosphoSite; Q13555; -.
DR DMDM; 62512173; -.
DR PaxDb; Q13555; -.
DR PRIDE; Q13555; -.
DR DNASU; 818; -.
DR Ensembl; ENST00000305762; ENSP00000307082; ENSG00000148660.
DR Ensembl; ENST00000322635; ENSP00000315599; ENSG00000148660.
DR Ensembl; ENST00000322680; ENSP00000319060; ENSG00000148660.
DR Ensembl; ENST00000351293; ENSP00000277853; ENSG00000148660.
DR Ensembl; ENST00000394762; ENSP00000378243; ENSG00000148660.
DR Ensembl; ENST00000423381; ENSP00000410298; ENSG00000148660.
DR GeneID; 818; -.
DR KEGG; hsa:818; -.
DR CTD; 818; -.
DR GeneCards; GC10M075572; -.
DR HGNC; HGNC:1463; CAMK2G.
DR MIM; 602123; gene.
DR neXtProt; NX_Q13555; -.
DR PharmGKB; PA93; -.
DR eggNOG; COG0515; -.
DR HOVERGEN; HBG108055; -.
DR InParanoid; Q13555; -.
DR KO; K04515; -.
DR OMA; RDCIPSV; -.
DR OrthoDB; EOG7ZD1VM; -.
DR Reactome; REACT_13685; Neuronal System.
DR Reactome; REACT_6900; Immune System.
DR SignaLink; Q13555; -.
DR ChiTaRS; CAMK2G; human.
DR EvolutionaryTrace; Q13555; -.
DR GeneWiki; CAMK2G; -.
DR GenomeRNAi; 818; -.
DR NextBio; 3340; -.
DR PRO; PR:Q13555; -.
DR ArrayExpress; Q13555; -.
DR Bgee; Q13555; -.
DR Genevestigator; Q13555; -.
DR GO; GO:0005954; C:calcium- and calmodulin-dependent protein kinase complex; TAS:UniProtKB.
DR GO; GO:0005829; C:cytosol; TAS:Reactome.
DR GO; GO:0030666; C:endocytic vesicle membrane; TAS:Reactome.
DR GO; GO:0005654; C:nucleoplasm; TAS:Reactome.
DR GO; GO:0005886; C:plasma membrane; TAS:Reactome.
DR GO; GO:0033017; C:sarcoplasmic reticulum membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0005524; F:ATP binding; NAS:UniProtKB.
DR GO; GO:0004723; F:calcium-dependent protein serine/threonine phosphatase activity; NAS:UniProtKB.
DR GO; GO:0005516; F:calmodulin binding; NAS:UniProtKB.
DR GO; GO:0004683; F:calmodulin-dependent protein kinase activity; IEA:UniProtKB-EC.
DR GO; GO:0006816; P:calcium ion transport; IEA:Ensembl.
DR GO; GO:0030154; P:cell differentiation; IEA:UniProtKB-KW.
DR GO; GO:0000082; P:G1/S transition of mitotic cell cycle; IEA:Ensembl.
DR GO; GO:0030073; P:insulin secretion; NAS:UniProtKB.
DR GO; GO:0060333; P:interferon-gamma-mediated signaling pathway; TAS:Reactome.
DR GO; GO:0007399; P:nervous system development; IEA:UniProtKB-KW.
DR GO; GO:0046777; P:protein autophosphorylation; IEA:Ensembl.
DR GO; GO:0006468; P:protein phosphorylation; NAS:UniProtKB.
DR GO; GO:0051924; P:regulation of calcium ion transport; TAS:UniProtKB.
DR GO; GO:0014733; P:regulation of skeletal muscle adaptation; TAS:UniProtKB.
DR GO; GO:0007268; P:synaptic transmission; TAS:Reactome.
DR InterPro; IPR020636; Ca/CaM-dep_Ca-dep_prot_Kinase.
DR InterPro; IPR013543; Ca/CaM-dep_prot_kinase-assoc.
DR InterPro; IPR011009; Kinase-like_dom.
DR InterPro; IPR000719; Prot_kinase_dom.
DR InterPro; IPR017441; Protein_kinase_ATP_BS.
DR InterPro; IPR002290; Ser/Thr_dual-sp_kinase_dom.
DR InterPro; IPR008271; Ser/Thr_kinase_AS.
DR PANTHER; PTHR24347; PTHR24347; 1.
DR Pfam; PF08332; CaMKII_AD; 1.
DR Pfam; PF00069; Pkinase; 1.
DR SMART; SM00220; S_TKc; 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 Complete proteome; Developmental protein; Differentiation; Kinase;
KW Membrane; Neurogenesis; Nucleotide-binding; Phosphoprotein;
KW Polymorphism; Reference proteome; Sarcoplasmic reticulum;
KW Serine/threonine-protein kinase; Transferase.
FT CHAIN 1 558 Calcium/calmodulin-dependent protein
FT kinase type II subunit gamma.
FT /FTId=PRO_0000086101.
FT DOMAIN 14 272 Protein kinase.
FT NP_BIND 20 28 ATP (By similarity).
FT REGION 283 292 Autoinhibitory domain.
FT REGION 291 301 Calmodulin-binding (By similarity).
FT REGION 294 316 Calmodulin-binding.
FT ACT_SITE 136 136 Proton acceptor (By similarity).
FT BINDING 43 43 ATP (By similarity).
FT MOD_RES 287 287 Phosphothreonine; by autocatalysis.
FT MOD_RES 306 306 Phosphothreonine; by autocatalysis (By
FT similarity).
FT MOD_RES 307 307 Phosphothreonine; by autocatalysis
FT (Probable).
FT MOD_RES 311 311 Phosphoserine.
FT MOD_RES 349 349 Phosphoserine.
FT MOD_RES 352 352 Phosphoserine.
FT MOD_RES 419 419 Phosphoserine.
FT VAR_SEQ 315 315 S -> SVGRQSSAPASPAASAAGLAGQ (in isoform 5
FT and isoform 6).
FT /FTId=VSP_032699.
FT VAR_SEQ 331 364 Missing (in isoform 3, isoform 7 and
FT isoform 10).
FT /FTId=VSP_013350.
FT VAR_SEQ 331 341 Missing (in isoform 2, isoform 8 and
FT isoform 9).
FT /FTId=VSP_013349.
FT VAR_SEQ 341 363 Missing (in isoform 5).
FT /FTId=VSP_032700.
FT VAR_SEQ 351 364 Missing (in isoform 9).
FT /FTId=VSP_036027.
FT VAR_SEQ 396 425 ARSPEGRSSRDRTAPSAGMQPQPSLCSSAM -> V (in
FT isoform 4, isoform 5 and isoform 10).
FT /FTId=VSP_004778.
FT VAR_SEQ 397 398 RS -> APLRTGNGSSV (in isoform 6, isoform
FT 7, isoform 8 and isoform 9).
FT /FTId=VSP_035456.
FT VARIANT 36 36 S -> P (in dbSNP:rs17853266).
FT /FTId=VAR_042430.
FT VARIANT 292 292 R -> P (found in a patient with severe
FT mental retardation, myopia, strabismus,
FT low ATP production and decreased
FT oxidation velocities).
FT /FTId=VAR_069390.
FT CONFLICT 230 230 A -> T (in Ref. 6; AAB61379).
FT HELIX 9 13
FT STRAND 14 22
FT STRAND 26 33
FT TURN 34 37
FT STRAND 38 46
FT HELIX 52 67
FT STRAND 76 81
FT STRAND 83 91
FT HELIX 98 103
FT HELIX 110 129
FT HELIX 139 141
FT STRAND 142 145
FT STRAND 153 155
FT HELIX 178 180
FT HELIX 183 187
FT HELIX 194 209
FT HELIX 219 227
FT HELIX 237 240
FT HELIX 243 252
FT TURN 257 259
FT HELIX 263 266
FT HELIX 270 273
FT HELIX 275 278
FT HELIX 285 301
FT HELIX 390 397
FT HELIX 427 443
FT HELIX 446 452
FT STRAND 453 460
FT HELIX 462 464
FT STRAND 468 470
FT HELIX 471 481
FT TURN 482 485
FT STRAND 490 501
FT STRAND 506 518
FT STRAND 524 538
FT STRAND 541 550
SQ SEQUENCE 558 AA; 62609 MW; 38D4112C2FDBD44C CRC64;
MATTATCTRF TDDYQLFEEL GKGAFSVVRR CVKKTSTQEY AAKIINTKKL SARDHQKLER
EARICRLLKH PNIVRLHDSI SEEGFHYLVF DLVTGGELFE DIVAREYYSE ADASHCIHQI
LESVNHIHQH DIVHRDLKPE NLLLASKCKG AAVKLADFGL AIEVQGEQQA WFGFAGTPGY
LSPEVLRKDP YGKPVDIWAC GVILYILLVG YPPFWDEDQH KLYQQIKAGA YDFPSPEWDT
VTPEAKNLIN QMLTINPAKR ITADQALKHP WVCQRSTVAS MMHRQETVEC LRKFNARRKL
KGAILTTMLV SRNFSAAKSL LNKKSDGGVK KRKSSSSVHL MPQSNNKNSL VSPAQEPAPL
QTAMEPQTTV VHNATDGIKG STESCNTTTE DEDLKARSPE GRSSRDRTAP SAGMQPQPSL
CSSAMRKQEI IKITEQLIEA INNGDFEAYT KICDPGLTSF EPEALGNLVE GMDFHKFYFE
NLLSKNSKPI HTTILNPHVH VIGEDAACIA YIRLTQYIDG QGRPRTSQSE ETRVWHRRDG
KWLNVHYHCS GAPAAPLQ
//
ID KCC2G_HUMAN Reviewed; 558 AA.
AC Q13555; O00561; O15378; Q13279; Q13282; Q13556; Q5SQZ3; Q5SQZ4;
read moreAC Q5SWX4; Q7KYX5; Q8N4I3; Q8NIA4;
DT 01-NOV-1997, integrated into UniProtKB/Swiss-Prot.
DT 12-APR-2005, sequence version 3.
DT 22-JAN-2014, entry version 140.
DE RecName: Full=Calcium/calmodulin-dependent protein kinase type II subunit gamma;
DE Short=CaM kinase II subunit gamma;
DE Short=CaMK-II subunit gamma;
DE EC=2.7.11.17;
GN Name=CAMK2G; Synonyms=CAMK, CAMK-II, CAMKG;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
OC Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini;
OC Catarrhini; Hominidae; Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=15164054; DOI=10.1038/nature02462;
RA Deloukas P., Earthrowl M.E., Grafham D.V., Rubenfield M., French L.,
RA Steward C.A., Sims S.K., Jones M.C., Searle S., Scott C., Howe K.,
RA Hunt S.E., Andrews T.D., Gilbert J.G.R., Swarbreck D., Ashurst J.L.,
RA Taylor A., Battles J., Bird C.P., Ainscough R., Almeida J.P.,
RA Ashwell R.I.S., Ambrose K.D., Babbage A.K., Bagguley C.L., Bailey J.,
RA Banerjee R., Bates K., Beasley H., Bray-Allen S., Brown A.J.,
RA Brown J.Y., Burford D.C., Burrill W., Burton J., Cahill P., Camire D.,
RA Carter N.P., Chapman J.C., Clark S.Y., Clarke G., Clee C.M., Clegg S.,
RA Corby N., Coulson A., Dhami P., Dutta I., Dunn M., Faulkner L.,
RA Frankish A., Frankland J.A., Garner P., Garnett J., Gribble S.,
RA Griffiths C., Grocock R., Gustafson E., Hammond S., Harley J.L.,
RA Hart E., Heath P.D., Ho T.P., Hopkins B., Horne J., Howden P.J.,
RA Huckle E., Hynds C., Johnson C., Johnson D., Kana A., Kay M.,
RA Kimberley A.M., Kershaw J.K., Kokkinaki M., Laird G.K., Lawlor S.,
RA Lee H.M., Leongamornlert D.A., Laird G., Lloyd C., Lloyd D.M.,
RA Loveland J., Lovell J., McLaren S., McLay K.E., McMurray A.,
RA Mashreghi-Mohammadi M., Matthews L., Milne S., Nickerson T.,
RA Nguyen M., Overton-Larty E., Palmer S.A., Pearce A.V., Peck A.I.,
RA Pelan S., Phillimore B., Porter K., Rice C.M., Rogosin A., Ross M.T.,
RA Sarafidou T., Sehra H.K., Shownkeen R., Skuce C.D., Smith M.,
RA Standring L., Sycamore N., Tester J., Thorpe A., Torcasso W.,
RA Tracey A., Tromans A., Tsolas J., Wall M., Walsh J., Wang H.,
RA Weinstock K., West A.P., Willey D.L., Whitehead S.L., Wilming L.,
RA Wray P.W., Young L., Chen Y., Lovering R.C., Moschonas N.K.,
RA Siebert R., Fechtel K., Bentley D., Durbin R.M., Hubbard T.,
RA Doucette-Stamm L., Beck S., Smith D.R., Rogers J.;
RT "The DNA sequence and comparative analysis of human chromosome 10.";
RL Nature 429:375-381(2004).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA], AND VARIANT PRO-36.
RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L.,
RA Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R.,
RA Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V.,
RA Hannenhalli S., Turner R., Yooseph S., Lu F., Nusskern D.R.,
RA Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H.,
RA Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G.,
RA Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W.,
RA Venter J.C.;
RL Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases.
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 5), AND VARIANT
RP PRO-36.
RC TISSUE=Brain;
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
RT project: the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [4]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 1-315.
RX PubMed=9240463; DOI=10.1006/bbrc.1997.6871;
RA Breen M.A., Ashcroft S.J.;
RT "Human islets of Langerhans express multiple isoforms of
RT calcium/calmodulin-dependent protein kinase II.";
RL Biochem. Biophys. Res. Commun. 236:473-478(1997).
RN [5]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 23-558, AND ALTERNATIVE SPLICING
RP (ISOFORM 6).
RX PubMed=12032636; DOI=10.1007/s00125-002-0779-8;
RA Gloyn A.L., Desai M., Clark A., Levy J.C., Holman R.R., Frayling T.M.,
RA Hattersley A.T., Ashcroft S.J.;
RT "Human calcium/calmodulin-dependent protein kinase II gamma: cloning,
RT genomic structure and detection of variants in subjects with type II
RT diabetes.";
RL Diabetologia 45:580-583(2002).
RN [6]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 66-436 (ISOFORM 10).
RX PubMed=8449910;
RA Nghiem P., Saati S.M., Martens C.L., Gardner P., Schulman H.;
RT "Cloning and analysis of two new isoforms of multifunctional
RT Ca2+/calmodulin-dependent protein kinase. Expression in multiple human
RT tissues.";
RL J. Biol. Chem. 268:5471-5479(1993).
RN [7]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 302-497 (ISOFORMS 2 AND 4).
RX PubMed=9060999; DOI=10.1016/S0167-4889(96)00141-3;
RA Tombes R.M., Krystal G.W.;
RT "Identification of novel human tumor cell-specific CaMK-II variants.";
RL Biochim. Biophys. Acta 1355:281-292(1997).
RN [8]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 326-432 (ISOFORMS 7; 8 AND 9).
RX PubMed=7557101;
RA Kwiatkowski A.P., McGill J.M.;
RT "Human biliary epithelial cell line Mz-ChA-1 expresses new isoforms of
RT calmodulin-dependent protein kinase II.";
RL Gastroenterology 109:1316-1323(1995).
RN [9]
RP ENZYME REGULATION, SUBUNIT, AND AUTOPHOSPHORYLATION.
RX PubMed=14722083; DOI=10.1074/jbc.M313597200;
RA Gaertner T.R., Kolodziej S.J., Wang D., Kobayashi R., Koomen J.M.,
RA Stoops J.K., Waxham M.N.;
RT "Comparative analyses of the three-dimensional structures and
RT enzymatic properties of alpha, beta, gamma and delta isoforms of Ca2+-
RT calmodulin-dependent protein kinase II.";
RL J. Biol. Chem. 279:12484-12494(2004).
RN [10]
RP FUNCTION IN SKELETAL MUSCLE, PHOSPHORYLATION AT THR-287, FUNCTION IN
RP PHOSPHORYLATION OF PLN, TISSUE SPECIFICITY, AND INDUCTION.
RX PubMed=16690701; DOI=10.1113/jphysiol.2006.111757;
RA Rose A.J., Kiens B., Richter E.A.;
RT "Ca2+-calmodulin-dependent protein kinase expression and signalling in
RT skeletal muscle during exercise.";
RL J. Physiol. (Lond.) 574:889-903(2006).
RN [11]
RP REVIEW ON FUNCTION IN SKELETAL MUSCLE.
RX PubMed=15294044; DOI=10.1079/PNS2004335;
RA Chin E.R.;
RT "The role of calcium and calcium/calmodulin-dependent kinases in
RT skeletal muscle plasticity and mitochondrial biogenesis.";
RL Proc. Nutrit. Soc. 63:279-286(2004).
RN [12]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-311; SER-349; SER-352
RP AND SER-419, PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-325
RP (ISOFORMS 10; 2; 3; 5; 6; 7; 8 AND 9), PHOSPHORYLATION [LARGE SCALE
RP ANALYSIS] AT SER-338 (ISOFORM 9), AND MASS SPECTROMETRY.
RC TISSUE=Cervix carcinoma;
RX PubMed=18691976; DOI=10.1016/j.molcel.2008.07.007;
RA Daub H., Olsen J.V., Bairlein M., Gnad F., Oppermann F.S., Korner R.,
RA Greff Z., Keri G., Stemmann O., Mann M.;
RT "Kinase-selective enrichment enables quantitative phosphoproteomics of
RT the kinome across the cell cycle.";
RL Mol. Cell 31:438-448(2008).
RN [13]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=18669648; DOI=10.1073/pnas.0805139105;
RA Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E.,
RA Elledge S.J., Gygi S.P.;
RT "A quantitative atlas of mitotic phosphorylation.";
RL Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008).
RN [14]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-287; SER-311; SER-352
RP AND SER-419, PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-325
RP (ISOFORMS 10; 2; 3; 7; 8 AND 9), AND MASS SPECTROMETRY.
RX PubMed=19369195; DOI=10.1074/mcp.M800588-MCP200;
RA Oppermann F.S., Gnad F., Olsen J.V., Hornberger R., Greff Z., Keri G.,
RA Mann M., Daub H.;
RT "Large-scale proteomics analysis of the human kinome.";
RL Mol. Cell. Proteomics 8:1751-1764(2009).
RN [15]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-311, AND MASS
RP SPECTROMETRY.
RC TISSUE=Cervix carcinoma;
RX PubMed=20068231; DOI=10.1126/scisignal.2000475;
RA Olsen J.V., Vermeulen M., Santamaria A., Kumar C., Miller M.L.,
RA Jensen L.J., Gnad F., Cox J., Jensen T.S., Nigg E.A., Brunak S.,
RA Mann M.;
RT "Quantitative phosphoproteomics reveals widespread full
RT phosphorylation site occupancy during mitosis.";
RL Sci. Signal. 3:RA3-RA3(2010).
RN [16]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=21269460; DOI=10.1186/1752-0509-5-17;
RA Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P.,
RA Buerckstuemmer T., Bennett K.L., Superti-Furga G., Colinge J.;
RT "Initial characterization of the human central proteome.";
RL BMC Syst. Biol. 5:17-17(2011).
RN [17]
RP X-RAY CRYSTALLOGRAPHY (2.25 ANGSTROMS) OF 5-315 AND 426-556 IN COMPLEX
RP WITH INHIBITOR.
RX PubMed=20668654; DOI=10.1371/journal.pbio.1000426;
RA Rellos P., Pike A.C., Niesen F.H., Salah E., Lee W.H., von Delft F.,
RA Knapp S.;
RT "Structure of the CaMKIIdelta/calmodulin complex reveals the molecular
RT mechanism of CaMKII kinase activation.";
RL PLoS Biol. 8:E1000426-E1000426(2010).
RN [18]
RP VARIANT PRO-292.
RX PubMed=23033978; DOI=10.1056/NEJMoa1206524;
RA de Ligt J., Willemsen M.H., van Bon B.W., Kleefstra T., Yntema H.G.,
RA Kroes T., Vulto-van Silfhout A.T., Koolen D.A., de Vries P.,
RA Gilissen C., del Rosario M., Hoischen A., Scheffer H., de Vries B.B.,
RA Brunner H.G., Veltman J.A., Vissers L.E.;
RT "Diagnostic exome sequencing in persons with severe intellectual
RT disability.";
RL N. Engl. J. Med. 367:1921-1929(2012).
CC -!- FUNCTION: Calcium/calmodulin-dependent protein kinase that
CC functions autonomously after Ca(2+)/calmodulin-binding and
CC autophosphorylation, and is involved in sarcoplsamic reticulum
CC Ca(2+) transport in skeletal muscle and may function in dendritic
CC spine and synapse formation and neuronal plasticity. In slow-
CC twitch muscles, is involved in regulation of sarcoplasmic
CC reticulum (SR) Ca(2+) transport and in fast-twitch muscle
CC participates in the control of Ca(2+) release from the SR through
CC phosphorylation of the ryanodine receptor-coupling factor triadin.
CC In neurons, may participate in the promotion of dendritic spine
CC and synapse formation and maintenance of synaptic plasticity which
CC enables long-term potentiation (LTP) and hippocampus-dependent
CC learning.
CC -!- CATALYTIC ACTIVITY: ATP + a protein = ADP + a phosphoprotein.
CC -!- ENZYME REGULATION: Activated by Ca(2+)/calmodulin. Binding of
CC calmodulin results in conformational change that relieves
CC intrasteric autoinhibition and allows autophosphorylation of Thr-
CC 287 which turns the kinase in a constitutively active form and
CC confers to the kinase a Ca(2+)-independent activity.
CC -!- SUBUNIT: CAMK2 is composed of 4 different chains: alpha (CAMK2A),
CC beta (CAMK2B), gamma (CAMK2G), and delta (CAMK2D). The different
CC isoforms assemble into homo- or heteromultimeric holoenzymes
CC composed of 12 subunits with two hexameric rings stacked one on
CC top of the other.
CC -!- INTERACTION:
CC P08238:HSP90AB1; NbExp=2; IntAct=EBI-1383465, EBI-352572;
CC -!- SUBCELLULAR LOCATION: Sarcoplasmic reticulum membrane; Peripheral
CC membrane protein; Cytoplasmic side (Probable).
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=10;
CC Name=1;
CC IsoId=Q13555-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q13555-2; Sequence=VSP_013349;
CC Note=Contains a phosphoserine at position 325;
CC Name=3;
CC IsoId=Q13555-3; Sequence=VSP_013350;
CC Note=Contains a phosphoserine at position 325;
CC Name=4;
CC IsoId=Q13555-4; Sequence=VSP_004778;
CC Name=5;
CC IsoId=Q13555-5; Sequence=VSP_032699, VSP_032700, VSP_004778;
CC Note=Contains a phosphoserine at position 325;
CC Name=6;
CC IsoId=Q13555-6; Sequence=VSP_032699, VSP_035456;
CC Note=Contains a phosphoserine at position 325;
CC Name=7; Synonyms=gamma F;
CC IsoId=Q13555-7; Sequence=VSP_013350, VSP_035456;
CC Note=Contains a phosphoserine at position 325;
CC Name=8; Synonyms=gamma E;
CC IsoId=Q13555-8; Sequence=VSP_013349, VSP_035456;
CC Note=Contains a phosphoserine at position 325;
CC Name=9; Synonyms=gamma D;
CC IsoId=Q13555-9; Sequence=VSP_013349, VSP_036027, VSP_035456;
CC Note=Contains a phosphoserine at position 325. Contains a
CC phosphoserine at position 338;
CC Name=10;
CC IsoId=Q13555-10; Sequence=VSP_013350, VSP_004778;
CC Note=Contains a phosphoserine at position 325;
CC -!- TISSUE SPECIFICITY: Expressed in skeletal muscle.
CC -!- INDUCTION: Activity is induced in skeletal muscle during exercise.
CC -!- DOMAIN: The CAMK2 protein kinases contain a unique C-terminal
CC subunit 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
CC into an activated state.
CC -!- SIMILARITY: Belongs to the protein kinase superfamily. CAMK
CC Ser/Thr protein kinase family. CaMK subfamily.
CC -!- SIMILARITY: Contains 1 protein kinase domain.
CC -!- SEQUENCE CAUTION:
CC Sequence=AAB61379.1; Type=Erroneous initiation; Note=Translation N-terminally extended;
CC -----------------------------------------------------------------------
CC Copyrighted by the UniProt Consortium, see http://www.uniprot.org/terms
CC Distributed under the Creative Commons Attribution-NoDerivs License
CC -----------------------------------------------------------------------
DR EMBL; AL713896; CAI13789.1; -; Genomic_DNA.
DR EMBL; AC022400; CAI13789.1; JOINED; Genomic_DNA.
DR EMBL; AL596247; CAI13789.1; JOINED; Genomic_DNA.
DR EMBL; AL713896; CAI13790.1; -; Genomic_DNA.
DR EMBL; AC022400; CAI13790.1; JOINED; Genomic_DNA.
DR EMBL; AL596247; CAI13790.1; JOINED; Genomic_DNA.
DR EMBL; AL713896; CAI13791.1; -; Genomic_DNA.
DR EMBL; AC022400; CAI13791.1; JOINED; Genomic_DNA.
DR EMBL; AL596247; CAI13791.1; JOINED; Genomic_DNA.
DR EMBL; AL596247; CAI13965.1; -; Genomic_DNA.
DR EMBL; AC022400; CAI13965.1; JOINED; Genomic_DNA.
DR EMBL; AL713896; CAI13965.1; JOINED; Genomic_DNA.
DR EMBL; AL596247; CAI13966.1; -; Genomic_DNA.
DR EMBL; AC022400; CAI13966.1; JOINED; Genomic_DNA.
DR EMBL; AL713896; CAI13966.1; JOINED; Genomic_DNA.
DR EMBL; AL596247; CAI13968.1; -; Genomic_DNA.
DR EMBL; AC022400; CAI13968.1; JOINED; Genomic_DNA.
DR EMBL; AL713896; CAI13968.1; JOINED; Genomic_DNA.
DR EMBL; CH471083; EAW54532.1; -; Genomic_DNA.
DR EMBL; CH471083; EAW54536.1; -; Genomic_DNA.
DR EMBL; BC034044; AAH34044.1; -; mRNA.
DR EMBL; U66064; AAB80848.1; -; mRNA.
DR EMBL; AH011636; AAM33514.1; -; Genomic_DNA.
DR EMBL; L07043; AAB61379.1; ALT_INIT; mRNA.
DR EMBL; U50359; AAB16864.1; -; mRNA.
DR EMBL; U50360; AAB16865.1; -; mRNA.
DR EMBL; U32472; AAA75201.1; -; mRNA.
DR EMBL; U32473; AAA75202.1; -; mRNA.
DR EMBL; U32509; AAA75203.1; -; mRNA.
DR PIR; G01975; G01975.
DR PIR; G01978; G01978.
DR RefSeq; NP_001213.2; NM_001222.3.
DR RefSeq; NP_751909.1; NM_172169.2.
DR RefSeq; NP_751913.1; NM_172173.2.
DR RefSeq; XP_005270258.1; XM_005270201.1.
DR RefSeq; XP_005270259.1; XM_005270202.1.
DR RefSeq; XP_005270260.1; XM_005270203.1.
DR UniGene; Hs.523045; -.
DR PDB; 2UX0; X-ray; 2.46 A; A/B/C/D/E/F=426-556.
DR PDB; 2V7O; X-ray; 2.25 A; A=5-315.
DR PDBsum; 2UX0; -.
DR PDBsum; 2V7O; -.
DR ProteinModelPortal; Q13555; -.
DR SMR; Q13555; 3-302, 387-552.
DR DIP; DIP-51315N; -.
DR IntAct; Q13555; 3.
DR BindingDB; Q13555; -.
DR ChEMBL; CHEMBL2097164; -.
DR GuidetoPHARMACOLOGY; 1557; -.
DR PhosphoSite; Q13555; -.
DR DMDM; 62512173; -.
DR PaxDb; Q13555; -.
DR PRIDE; Q13555; -.
DR DNASU; 818; -.
DR Ensembl; ENST00000305762; ENSP00000307082; ENSG00000148660.
DR Ensembl; ENST00000322635; ENSP00000315599; ENSG00000148660.
DR Ensembl; ENST00000322680; ENSP00000319060; ENSG00000148660.
DR Ensembl; ENST00000351293; ENSP00000277853; ENSG00000148660.
DR Ensembl; ENST00000394762; ENSP00000378243; ENSG00000148660.
DR Ensembl; ENST00000423381; ENSP00000410298; ENSG00000148660.
DR GeneID; 818; -.
DR KEGG; hsa:818; -.
DR CTD; 818; -.
DR GeneCards; GC10M075572; -.
DR HGNC; HGNC:1463; CAMK2G.
DR MIM; 602123; gene.
DR neXtProt; NX_Q13555; -.
DR PharmGKB; PA93; -.
DR eggNOG; COG0515; -.
DR HOVERGEN; HBG108055; -.
DR InParanoid; Q13555; -.
DR KO; K04515; -.
DR OMA; RDCIPSV; -.
DR OrthoDB; EOG7ZD1VM; -.
DR Reactome; REACT_13685; Neuronal System.
DR Reactome; REACT_6900; Immune System.
DR SignaLink; Q13555; -.
DR ChiTaRS; CAMK2G; human.
DR EvolutionaryTrace; Q13555; -.
DR GeneWiki; CAMK2G; -.
DR GenomeRNAi; 818; -.
DR NextBio; 3340; -.
DR PRO; PR:Q13555; -.
DR ArrayExpress; Q13555; -.
DR Bgee; Q13555; -.
DR Genevestigator; Q13555; -.
DR GO; GO:0005954; C:calcium- and calmodulin-dependent protein kinase complex; TAS:UniProtKB.
DR GO; GO:0005829; C:cytosol; TAS:Reactome.
DR GO; GO:0030666; C:endocytic vesicle membrane; TAS:Reactome.
DR GO; GO:0005654; C:nucleoplasm; TAS:Reactome.
DR GO; GO:0005886; C:plasma membrane; TAS:Reactome.
DR GO; GO:0033017; C:sarcoplasmic reticulum membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0005524; F:ATP binding; NAS:UniProtKB.
DR GO; GO:0004723; F:calcium-dependent protein serine/threonine phosphatase activity; NAS:UniProtKB.
DR GO; GO:0005516; F:calmodulin binding; NAS:UniProtKB.
DR GO; GO:0004683; F:calmodulin-dependent protein kinase activity; IEA:UniProtKB-EC.
DR GO; GO:0006816; P:calcium ion transport; IEA:Ensembl.
DR GO; GO:0030154; P:cell differentiation; IEA:UniProtKB-KW.
DR GO; GO:0000082; P:G1/S transition of mitotic cell cycle; IEA:Ensembl.
DR GO; GO:0030073; P:insulin secretion; NAS:UniProtKB.
DR GO; GO:0060333; P:interferon-gamma-mediated signaling pathway; TAS:Reactome.
DR GO; GO:0007399; P:nervous system development; IEA:UniProtKB-KW.
DR GO; GO:0046777; P:protein autophosphorylation; IEA:Ensembl.
DR GO; GO:0006468; P:protein phosphorylation; NAS:UniProtKB.
DR GO; GO:0051924; P:regulation of calcium ion transport; TAS:UniProtKB.
DR GO; GO:0014733; P:regulation of skeletal muscle adaptation; TAS:UniProtKB.
DR GO; GO:0007268; P:synaptic transmission; TAS:Reactome.
DR InterPro; IPR020636; Ca/CaM-dep_Ca-dep_prot_Kinase.
DR InterPro; IPR013543; Ca/CaM-dep_prot_kinase-assoc.
DR InterPro; IPR011009; Kinase-like_dom.
DR InterPro; IPR000719; Prot_kinase_dom.
DR InterPro; IPR017441; Protein_kinase_ATP_BS.
DR InterPro; IPR002290; Ser/Thr_dual-sp_kinase_dom.
DR InterPro; IPR008271; Ser/Thr_kinase_AS.
DR PANTHER; PTHR24347; PTHR24347; 1.
DR Pfam; PF08332; CaMKII_AD; 1.
DR Pfam; PF00069; Pkinase; 1.
DR SMART; SM00220; S_TKc; 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 Complete proteome; Developmental protein; Differentiation; Kinase;
KW Membrane; Neurogenesis; Nucleotide-binding; Phosphoprotein;
KW Polymorphism; Reference proteome; Sarcoplasmic reticulum;
KW Serine/threonine-protein kinase; Transferase.
FT CHAIN 1 558 Calcium/calmodulin-dependent protein
FT kinase type II subunit gamma.
FT /FTId=PRO_0000086101.
FT DOMAIN 14 272 Protein kinase.
FT NP_BIND 20 28 ATP (By similarity).
FT REGION 283 292 Autoinhibitory domain.
FT REGION 291 301 Calmodulin-binding (By similarity).
FT REGION 294 316 Calmodulin-binding.
FT ACT_SITE 136 136 Proton acceptor (By similarity).
FT BINDING 43 43 ATP (By similarity).
FT MOD_RES 287 287 Phosphothreonine; by autocatalysis.
FT MOD_RES 306 306 Phosphothreonine; by autocatalysis (By
FT similarity).
FT MOD_RES 307 307 Phosphothreonine; by autocatalysis
FT (Probable).
FT MOD_RES 311 311 Phosphoserine.
FT MOD_RES 349 349 Phosphoserine.
FT MOD_RES 352 352 Phosphoserine.
FT MOD_RES 419 419 Phosphoserine.
FT VAR_SEQ 315 315 S -> SVGRQSSAPASPAASAAGLAGQ (in isoform 5
FT and isoform 6).
FT /FTId=VSP_032699.
FT VAR_SEQ 331 364 Missing (in isoform 3, isoform 7 and
FT isoform 10).
FT /FTId=VSP_013350.
FT VAR_SEQ 331 341 Missing (in isoform 2, isoform 8 and
FT isoform 9).
FT /FTId=VSP_013349.
FT VAR_SEQ 341 363 Missing (in isoform 5).
FT /FTId=VSP_032700.
FT VAR_SEQ 351 364 Missing (in isoform 9).
FT /FTId=VSP_036027.
FT VAR_SEQ 396 425 ARSPEGRSSRDRTAPSAGMQPQPSLCSSAM -> V (in
FT isoform 4, isoform 5 and isoform 10).
FT /FTId=VSP_004778.
FT VAR_SEQ 397 398 RS -> APLRTGNGSSV (in isoform 6, isoform
FT 7, isoform 8 and isoform 9).
FT /FTId=VSP_035456.
FT VARIANT 36 36 S -> P (in dbSNP:rs17853266).
FT /FTId=VAR_042430.
FT VARIANT 292 292 R -> P (found in a patient with severe
FT mental retardation, myopia, strabismus,
FT low ATP production and decreased
FT oxidation velocities).
FT /FTId=VAR_069390.
FT CONFLICT 230 230 A -> T (in Ref. 6; AAB61379).
FT HELIX 9 13
FT STRAND 14 22
FT STRAND 26 33
FT TURN 34 37
FT STRAND 38 46
FT HELIX 52 67
FT STRAND 76 81
FT STRAND 83 91
FT HELIX 98 103
FT HELIX 110 129
FT HELIX 139 141
FT STRAND 142 145
FT STRAND 153 155
FT HELIX 178 180
FT HELIX 183 187
FT HELIX 194 209
FT HELIX 219 227
FT HELIX 237 240
FT HELIX 243 252
FT TURN 257 259
FT HELIX 263 266
FT HELIX 270 273
FT HELIX 275 278
FT HELIX 285 301
FT HELIX 390 397
FT HELIX 427 443
FT HELIX 446 452
FT STRAND 453 460
FT HELIX 462 464
FT STRAND 468 470
FT HELIX 471 481
FT TURN 482 485
FT STRAND 490 501
FT STRAND 506 518
FT STRAND 524 538
FT STRAND 541 550
SQ SEQUENCE 558 AA; 62609 MW; 38D4112C2FDBD44C CRC64;
MATTATCTRF TDDYQLFEEL GKGAFSVVRR CVKKTSTQEY AAKIINTKKL SARDHQKLER
EARICRLLKH PNIVRLHDSI SEEGFHYLVF DLVTGGELFE DIVAREYYSE ADASHCIHQI
LESVNHIHQH DIVHRDLKPE NLLLASKCKG AAVKLADFGL AIEVQGEQQA WFGFAGTPGY
LSPEVLRKDP YGKPVDIWAC GVILYILLVG YPPFWDEDQH KLYQQIKAGA YDFPSPEWDT
VTPEAKNLIN QMLTINPAKR ITADQALKHP WVCQRSTVAS MMHRQETVEC LRKFNARRKL
KGAILTTMLV SRNFSAAKSL LNKKSDGGVK KRKSSSSVHL MPQSNNKNSL VSPAQEPAPL
QTAMEPQTTV VHNATDGIKG STESCNTTTE DEDLKARSPE GRSSRDRTAP SAGMQPQPSL
CSSAMRKQEI IKITEQLIEA INNGDFEAYT KICDPGLTSF EPEALGNLVE GMDFHKFYFE
NLLSKNSKPI HTTILNPHVH VIGEDAACIA YIRLTQYIDG QGRPRTSQSE ETRVWHRRDG
KWLNVHYHCS GAPAAPLQ
//
MIM
602123
*RECORD*
*FIELD* NO
602123
*FIELD* TI
*602123 CALCIUM/CALMODULIN-DEPENDENT PROTEIN KINASE II-GAMMA; CAMK2G
;;CaM KINASE II GAMMA SUBUNIT;;
read moreCAMKG
*FIELD* TX
DESCRIPTION
Calcium/calmodulin-dependent protein kinase II (CaM kinase II) is a
ubiquitous serine/threonine protein kinase that has been implicated in
diverse effects of hormones and neurotransmitters that utilize Ca(2+) as
a second messenger. The enzyme is an oligomeric protein composed of
distinct but related subunits, alpha (114078), beta (607707), gamma, and
delta (607708), each encoded by a separate gene. Each subunit has
alternatively spliced variants.
CLONING
Breen and Ashcroft (1997) cloned and sequenced a novel CaM kinase
II-gamma cDNA from human islet cell RNA. This isoform, designated
gamma-SRP by the authors, encodes a truncated gamma CaM kinase II in
which the 3-prime end consists of 804 basepairs of the human SRP72 gene
(602122).
Tombes and Krystal (1997) identified a number of CAMKG variants
expressed by neuronal cells. Two variants were consistently expressed in
nonneuronal cell lines, and another was preferentially expressed in
tumor cells.
MAPPING
Using somatic cell hybrid analysis and fluorescence in situ
hybridization, Li et al. (1994) mapped the CAMK2G gene to human
chromosome 10q22. Ahmed et al. (2001) stated that CAMK2G is 1 of 3 genes
that are nested in the introns of PCDH15 (605514).
GENE FUNCTION
In mouse cardiomyocytes, Zhu et al. (2003) demonstrated that
beta-1-adrenergic receptor (ADRB1; 109630)-induced apoptosis was
resistant to inhibition of PKA (see 176911). Rather, the Adrb1
proapoptotic effect was associated with non-Pka-dependent increases in
intracellular Ca(2+) and Camk2 activity. Blocking the L-type Ca(2+)
channel (see 114205), buffering intracellular Ca(2+), or inhibiting
Camk2 activity fully protected cardiomyocytes against Adrb1-induced
apoptosis; overexpressing the c splice variant of Camk2d markedly
exaggerated the Adrb1 apoptotic effect. Zhu et al. (2003) concluded that
CAMK2 constitutes a PKA-independent linkage of ADRB1 stimulation to
cardiomyocyte apoptosis.
Among 304 Swiss individuals tested and genotyped, de Quervain and
Papassotiropoulos (2006) found a significant association (p = 0.00008)
between short-term episodic memory performance and genetic variations in
a 7-gene cluster consisting of the ADCY8 (103070), PRKACG (176893),
CAMK2G, GRIN2A (138253), GRIN2B (138252), GRM3 (601115), and PRKCA
(176960) genes, all of which have well-established molecular and
biologic functions in animal memory. Functional MRI studies in an
independent set of 32 individuals with similar memory performance showed
a correlation between activation in memory-related brain regions,
including the hippocampus and parahippocampal gyrus, and genetic
variability in the 7-gene cluster. De Quervain and Papassotiropoulos
(2006) concluded that these 7 genes encode proteins of the memory
formation signaling cascade that are important for human memory
function.
MOLECULAR GENETICS
For discussion of mutation in the CAMK2G gene as a possible cause of an
intellectual disability phenotype, see 602123.0001.
ANIMAL MODEL
To study the role of CaMKII in T cells, Bui et al. (2000) generated
transgenic mice expressing a partially calcium-independent mutant form
of CAMKG (thr287 to asp). The size of the thymus was increased 1.5- to
2-fold in these mice, at least in part due to an increase in the life
span of double-positive thymocytes. There was an increase in the number
of T cells in the secondary lymphoid organs that had acquired an
antigen-dependent memory phenotype. These T cells were bona fide memory
cells as assessed by a variety of criteria. In addition, T cells from
wildtype mice acquired calcium-independent CaMKII activity after several
rounds of antigen-stimulated division. The authors proposed that CaMKII
controls a distinct process of activation-induced cellular
differentiation.
Using gene targeting, Zhang et al. (2005) developed a mouse model of
cardiac Camk2 inhibition and demonstrated substantial prevention of
maladaptive remodeling from excessive beta-adrenergic receptor
stimulation and myocardial infarction, and induction of balanced changes
in excitation-contraction coupling that preserved baseline and
beta-adrenergic receptor-stimulated physiologic increases in cardiac
function. Zhang et al. (2005) concluded that CAMK2 is a determinant of
clinically important heart disease phenotypes.
*FIELD* AV
.0001
VARIANT OF UNKNOWN SIGNIFICANCE
CAMK2G, ARG292PRO
This variant is classified as a variant of unknown significance because
its contribution to intellectual disability has not been confirmed.
In a boy with severe intellectual disability with self mutilation,
myopia, strabismus, mitochondrial dysfunction without mitochondrial gene
defects, short stature, flat face with narrow forehead, long palpebral
fissures, arched eyebrows, sacral dimple, short hands, brachydactyly,
and short feet, de Ligt et al. (2012) identified a de novo heterozygous
875G-C transversion resulting in an arg29-to-pro (R29P) substitution.
The patient had normal array and MLL2 testing.
*FIELD* RF
1. Ahmed, Z. M.; Riazuddin, S.; Bernstein, S. L.; Ahmed, Z.; Khan,
S.; Griffith, A. J.; Morell, R. J.; Friedman, T. B.; Riazuddin, S.;
Wilcox, E. R.: Mutations of the protocadherin gene PCDH15 cause Usher
syndrome type 1F. Am. J. Hum. Genet. 69: 25-34, 2001.
2. Breen, M. A.; Ashcroft, S. J. H.: A truncated isoform of Ca(2+)/calmodulin-dependent
protein kinase II expressed in human islets of Langerhans may result
from trans-splicing. FEBS Lett. 409: 375-379, 1997.
3. Bui, J. D.; Calbo, S.; Hayden-Martinez, K.; Kane, L. P.; Gardner,
P.; Hedrick, S. M.: A role for CaMKII in T cell memory. Cell 100:
457-467, 2000.
4. de Ligt, J.; Willemsen, M. H.; van Bon, B. W. M.; Kleefstra, T.;
Yntema, H. G.; Kroes, T.; Vulto-van Silfhout, A. T.; Koolen, D. A.;
de Vries, P.; Gilissen, C.; del Rosario, M.; Hoischen, A.; Scheffer,
H.; de Vries, B. B. A.; Brunner, H. G.; Veltman, J. A.; Vissers, L.
E. L. M.: Diagnostic exome sequencing in persons with severe intellectual
disability. New Eng. J. Med. 367: 1921-1929, 2012.
5. de Quervain, D. J.-F.; Papassotiropoulos, A.: Identification of
a genetic cluster influencing memory performance and hippocampal activity
in humans. Proc. Nat. Acad. Sci. 103: 4270-4274, 2006.
6. Li, X.; Nghiem, P.; Schulman, H.; Francke, U.: Localization of
the CAMKG gene encoding gamma isoforms of multifunctional calcium/calmodulin-dependent
protein kinase (CaM kinase) to human chromosome 10 band q22 and mouse
chromosome 14. Cytogenet. Cell Genet. 66: 113-116, 1994.
7. Tombes, R. M.; Krystal, G. W.: Identification of novel human tumor
cell-specific CaMK-II variants. Biochim. Biophys. Acta 1355: 281-292,
1997.
8. Zhang, R.; Khoo, M. S. C.; Wu, Y.; Yang, Y.; Grueter, C. E.; Ni,
G.; Price, E. E., Jr.; Thiel, W.; Guatimosim, S.; Song, L.-S.; Madu,
E. C.; Shah, A. N.; Vishnivetskaya, T. A.; Atkinson, J. B.; Gurevich,
V. V.; Salama, G.; Lederer, W. J.; Colbran, R. J.; Anderson, M. E.
: Calmodulin kinase II inhibition protects against structural heart
disease. Nature Med. 11: 409-417, 2005.
9. Zhu, W.-Z.; Wang, S.-Q.; Chakir, K.; Yang, D.; Zhang, T.; Brown,
J. H.; Devic, E.; Kobilka, B. K.; Cheng, H.; Xiao, R.-P.: Linkage
of beta-1-adrenergic stimulation to apoptotic heart cell death through
protein kinase A-independent activation of Ca(2+)/calmodulin kinase
II. J. Clin. Invest. 111: 617-625, 2003.
*FIELD* CN
Ada Hamosh - updated: 2/13/2013
Cassandra L. Kniffin - updated: 4/3/2006
Marla J. F. O'Neill - updated: 4/27/2005
Patricia A. Hartz - updated: 4/23/2003
Victor A. McKusick - updated: 8/15/2001
Stylianos E. Antonarakis - updated: 4/5/2000
*FIELD* CD
Jennifer P. Macke: 11/14/1997
*FIELD* ED
carol: 02/13/2013
carol: 2/13/2013
wwang: 4/17/2006
ckniffin: 4/3/2006
wwang: 12/20/2005
terry: 10/12/2005
wwang: 5/13/2005
wwang: 5/2/2005
terry: 4/27/2005
joanna: 4/19/2005
mgross: 4/23/2003
tkritzer: 3/28/2003
cwells: 9/6/2001
cwells: 8/23/2001
terry: 8/15/2001
mgross: 4/5/2000
alopez: 2/22/1999
dholmes: 11/20/1997
dholmes: 11/19/1997
dholmes: 11/14/1997
*RECORD*
*FIELD* NO
602123
*FIELD* TI
*602123 CALCIUM/CALMODULIN-DEPENDENT PROTEIN KINASE II-GAMMA; CAMK2G
;;CaM KINASE II GAMMA SUBUNIT;;
read moreCAMKG
*FIELD* TX
DESCRIPTION
Calcium/calmodulin-dependent protein kinase II (CaM kinase II) is a
ubiquitous serine/threonine protein kinase that has been implicated in
diverse effects of hormones and neurotransmitters that utilize Ca(2+) as
a second messenger. The enzyme is an oligomeric protein composed of
distinct but related subunits, alpha (114078), beta (607707), gamma, and
delta (607708), each encoded by a separate gene. Each subunit has
alternatively spliced variants.
CLONING
Breen and Ashcroft (1997) cloned and sequenced a novel CaM kinase
II-gamma cDNA from human islet cell RNA. This isoform, designated
gamma-SRP by the authors, encodes a truncated gamma CaM kinase II in
which the 3-prime end consists of 804 basepairs of the human SRP72 gene
(602122).
Tombes and Krystal (1997) identified a number of CAMKG variants
expressed by neuronal cells. Two variants were consistently expressed in
nonneuronal cell lines, and another was preferentially expressed in
tumor cells.
MAPPING
Using somatic cell hybrid analysis and fluorescence in situ
hybridization, Li et al. (1994) mapped the CAMK2G gene to human
chromosome 10q22. Ahmed et al. (2001) stated that CAMK2G is 1 of 3 genes
that are nested in the introns of PCDH15 (605514).
GENE FUNCTION
In mouse cardiomyocytes, Zhu et al. (2003) demonstrated that
beta-1-adrenergic receptor (ADRB1; 109630)-induced apoptosis was
resistant to inhibition of PKA (see 176911). Rather, the Adrb1
proapoptotic effect was associated with non-Pka-dependent increases in
intracellular Ca(2+) and Camk2 activity. Blocking the L-type Ca(2+)
channel (see 114205), buffering intracellular Ca(2+), or inhibiting
Camk2 activity fully protected cardiomyocytes against Adrb1-induced
apoptosis; overexpressing the c splice variant of Camk2d markedly
exaggerated the Adrb1 apoptotic effect. Zhu et al. (2003) concluded that
CAMK2 constitutes a PKA-independent linkage of ADRB1 stimulation to
cardiomyocyte apoptosis.
Among 304 Swiss individuals tested and genotyped, de Quervain and
Papassotiropoulos (2006) found a significant association (p = 0.00008)
between short-term episodic memory performance and genetic variations in
a 7-gene cluster consisting of the ADCY8 (103070), PRKACG (176893),
CAMK2G, GRIN2A (138253), GRIN2B (138252), GRM3 (601115), and PRKCA
(176960) genes, all of which have well-established molecular and
biologic functions in animal memory. Functional MRI studies in an
independent set of 32 individuals with similar memory performance showed
a correlation between activation in memory-related brain regions,
including the hippocampus and parahippocampal gyrus, and genetic
variability in the 7-gene cluster. De Quervain and Papassotiropoulos
(2006) concluded that these 7 genes encode proteins of the memory
formation signaling cascade that are important for human memory
function.
MOLECULAR GENETICS
For discussion of mutation in the CAMK2G gene as a possible cause of an
intellectual disability phenotype, see 602123.0001.
ANIMAL MODEL
To study the role of CaMKII in T cells, Bui et al. (2000) generated
transgenic mice expressing a partially calcium-independent mutant form
of CAMKG (thr287 to asp). The size of the thymus was increased 1.5- to
2-fold in these mice, at least in part due to an increase in the life
span of double-positive thymocytes. There was an increase in the number
of T cells in the secondary lymphoid organs that had acquired an
antigen-dependent memory phenotype. These T cells were bona fide memory
cells as assessed by a variety of criteria. In addition, T cells from
wildtype mice acquired calcium-independent CaMKII activity after several
rounds of antigen-stimulated division. The authors proposed that CaMKII
controls a distinct process of activation-induced cellular
differentiation.
Using gene targeting, Zhang et al. (2005) developed a mouse model of
cardiac Camk2 inhibition and demonstrated substantial prevention of
maladaptive remodeling from excessive beta-adrenergic receptor
stimulation and myocardial infarction, and induction of balanced changes
in excitation-contraction coupling that preserved baseline and
beta-adrenergic receptor-stimulated physiologic increases in cardiac
function. Zhang et al. (2005) concluded that CAMK2 is a determinant of
clinically important heart disease phenotypes.
*FIELD* AV
.0001
VARIANT OF UNKNOWN SIGNIFICANCE
CAMK2G, ARG292PRO
This variant is classified as a variant of unknown significance because
its contribution to intellectual disability has not been confirmed.
In a boy with severe intellectual disability with self mutilation,
myopia, strabismus, mitochondrial dysfunction without mitochondrial gene
defects, short stature, flat face with narrow forehead, long palpebral
fissures, arched eyebrows, sacral dimple, short hands, brachydactyly,
and short feet, de Ligt et al. (2012) identified a de novo heterozygous
875G-C transversion resulting in an arg29-to-pro (R29P) substitution.
The patient had normal array and MLL2 testing.
*FIELD* RF
1. Ahmed, Z. M.; Riazuddin, S.; Bernstein, S. L.; Ahmed, Z.; Khan,
S.; Griffith, A. J.; Morell, R. J.; Friedman, T. B.; Riazuddin, S.;
Wilcox, E. R.: Mutations of the protocadherin gene PCDH15 cause Usher
syndrome type 1F. Am. J. Hum. Genet. 69: 25-34, 2001.
2. Breen, M. A.; Ashcroft, S. J. H.: A truncated isoform of Ca(2+)/calmodulin-dependent
protein kinase II expressed in human islets of Langerhans may result
from trans-splicing. FEBS Lett. 409: 375-379, 1997.
3. Bui, J. D.; Calbo, S.; Hayden-Martinez, K.; Kane, L. P.; Gardner,
P.; Hedrick, S. M.: A role for CaMKII in T cell memory. Cell 100:
457-467, 2000.
4. de Ligt, J.; Willemsen, M. H.; van Bon, B. W. M.; Kleefstra, T.;
Yntema, H. G.; Kroes, T.; Vulto-van Silfhout, A. T.; Koolen, D. A.;
de Vries, P.; Gilissen, C.; del Rosario, M.; Hoischen, A.; Scheffer,
H.; de Vries, B. B. A.; Brunner, H. G.; Veltman, J. A.; Vissers, L.
E. L. M.: Diagnostic exome sequencing in persons with severe intellectual
disability. New Eng. J. Med. 367: 1921-1929, 2012.
5. de Quervain, D. J.-F.; Papassotiropoulos, A.: Identification of
a genetic cluster influencing memory performance and hippocampal activity
in humans. Proc. Nat. Acad. Sci. 103: 4270-4274, 2006.
6. Li, X.; Nghiem, P.; Schulman, H.; Francke, U.: Localization of
the CAMKG gene encoding gamma isoforms of multifunctional calcium/calmodulin-dependent
protein kinase (CaM kinase) to human chromosome 10 band q22 and mouse
chromosome 14. Cytogenet. Cell Genet. 66: 113-116, 1994.
7. Tombes, R. M.; Krystal, G. W.: Identification of novel human tumor
cell-specific CaMK-II variants. Biochim. Biophys. Acta 1355: 281-292,
1997.
8. Zhang, R.; Khoo, M. S. C.; Wu, Y.; Yang, Y.; Grueter, C. E.; Ni,
G.; Price, E. E., Jr.; Thiel, W.; Guatimosim, S.; Song, L.-S.; Madu,
E. C.; Shah, A. N.; Vishnivetskaya, T. A.; Atkinson, J. B.; Gurevich,
V. V.; Salama, G.; Lederer, W. J.; Colbran, R. J.; Anderson, M. E.
: Calmodulin kinase II inhibition protects against structural heart
disease. Nature Med. 11: 409-417, 2005.
9. Zhu, W.-Z.; Wang, S.-Q.; Chakir, K.; Yang, D.; Zhang, T.; Brown,
J. H.; Devic, E.; Kobilka, B. K.; Cheng, H.; Xiao, R.-P.: Linkage
of beta-1-adrenergic stimulation to apoptotic heart cell death through
protein kinase A-independent activation of Ca(2+)/calmodulin kinase
II. J. Clin. Invest. 111: 617-625, 2003.
*FIELD* CN
Ada Hamosh - updated: 2/13/2013
Cassandra L. Kniffin - updated: 4/3/2006
Marla J. F. O'Neill - updated: 4/27/2005
Patricia A. Hartz - updated: 4/23/2003
Victor A. McKusick - updated: 8/15/2001
Stylianos E. Antonarakis - updated: 4/5/2000
*FIELD* CD
Jennifer P. Macke: 11/14/1997
*FIELD* ED
carol: 02/13/2013
carol: 2/13/2013
wwang: 4/17/2006
ckniffin: 4/3/2006
wwang: 12/20/2005
terry: 10/12/2005
wwang: 5/13/2005
wwang: 5/2/2005
terry: 4/27/2005
joanna: 4/19/2005
mgross: 4/23/2003
tkritzer: 3/28/2003
cwells: 9/6/2001
cwells: 8/23/2001
terry: 8/15/2001
mgross: 4/5/2000
alopez: 2/22/1999
dholmes: 11/20/1997
dholmes: 11/19/1997
dholmes: 11/14/1997