KCC2G_HUMAN
ID KCC2G_HUMAN Reviewed; 558 AA.
AC Q13555; A0A0A0MS52; A0A0A0MT11; O00561; O15378; Q13279; Q13282; Q13556;
AC Q5SQZ3; Q5SQZ4; Q5SWX4; Q7KYX5; Q8N4I3; Q8NIA4;
DT 01-NOV-1997, integrated into UniProtKB/Swiss-Prot.
DT 28-MAR-2018, sequence version 4.
DT 03-AUG-2022, entry version 213.
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; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC 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., Brown J.Y.,
RA Burford D.C., Burrill W., Burton J., Cahill P., Camire D., Carter N.P.,
RA Chapman J.C., Clark S.Y., Clarke G., Clee C.M., Clegg S., Corby N.,
RA Coulson A., Dhami P., Dutta I., Dunn M., Faulkner L., Frankish A.,
RA Frankland J.A., Garner P., Garnett J., Gribble S., Griffiths C.,
RA Grocock R., Gustafson E., Hammond S., Harley J.L., Hart E., Heath P.D.,
RA Ho T.P., Hopkins B., Horne J., Howden P.J., Huckle E., Hynds C.,
RA Johnson C., Johnson D., Kana A., Kay M., Kimberley A.M., Kershaw J.K.,
RA Kokkinaki M., Laird G.K., Lawlor S., Lee H.M., Leongamornlert D.A.,
RA Laird G., Lloyd C., Lloyd D.M., Loveland J., Lovell J., McLaren S.,
RA McLay K.E., McMurray A., Mashreghi-Mohammadi M., Matthews L., Milne S.,
RA Nickerson T., Nguyen M., Overton-Larty E., Palmer S.A., Pearce A.V.,
RA Peck A.I., Pelan S., Phillimore B., Porter K., Rice C.M., Rogosin A.,
RA Ross M.T., Sarafidou T., Sehra H.K., Shownkeen R., Skuce C.D., Smith M.,
RA Standring L., Sycamore N., Tester J., Thorpe A., Torcasso W., Tracey A.,
RA Tromans A., Tsolas J., Wall M., Walsh J., Wang H., Weinstock K., West A.P.,
RA Willey D.L., Whitehead S.L., Wilming L., Wray P.W., Young L., Chen Y.,
RA Lovering R.C., Moschonas N.K., Siebert R., Fechtel K., Bentley D.,
RA Durbin R.M., Hubbard T., 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., Mobarry C.M.,
RA Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J.,
RA Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S.,
RA Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H.,
RA Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K.,
RA Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D.,
RA Hunkapiller M.W., Myers E.W., 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 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 project:
RT 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; DOI=10.1016/s0021-9258(18)53345-7;
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; DOI=10.1016/0016-5085(95)90594-4;
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 ACTIVITY 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 enzymatic
RT properties of alpha, beta, gamma and delta isoforms of Ca2+-calmodulin-
RT 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 skeletal
RT muscle plasticity and mitochondrial biogenesis.";
RL Proc. Nutr. Soc. 63:279-286(2004).
RN [12]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-311; SER-349; SER-352 AND
RP SER-419, PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-325 (ISOFORMS 10;
RP 11; 2; 3; 5; 6; 7; 8 AND 9), PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT
RP SER-346 (ISOFORM 11), PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-338
RP (ISOFORM 9), AND IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE
RP ANALYSIS].
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 the
RT 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 AND
RP SER-419, PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-325 (ISOFORMS 10; 2;
RP 3; 7; 8 AND 9), PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-346 (ISOFORM
RP 11), AND IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
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 IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
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., Mann M.;
RT "Quantitative phosphoproteomics reveals widespread full phosphorylation
RT 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., Buerckstuemmer T.,
RA 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 PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-287 AND SER-419, AND
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma, and Erythroleukemia;
RX PubMed=23186163; DOI=10.1021/pr300630k;
RA Zhou H., Di Palma S., Preisinger C., Peng M., Polat A.N., Heck A.J.,
RA Mohammed S.;
RT "Toward a comprehensive characterization of a human cancer cell
RT phosphoproteome.";
RL J. Proteome Res. 12:260-271(2013).
RN [18]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-419, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Liver;
RX PubMed=24275569; DOI=10.1016/j.jprot.2013.11.014;
RA Bian Y., Song C., Cheng K., Dong M., Wang F., Huang J., Sun D., Wang L.,
RA Ye M., Zou H.;
RT "An enzyme assisted RP-RPLC approach for in-depth analysis of human liver
RT phosphoproteome.";
RL J. Proteomics 96:253-262(2014).
RN [19]
RP X-RAY CRYSTALLOGRAPHY (2.25 ANGSTROMS) OF 5-315 AND 426-556 IN COMPLEX WITH
RP 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 [20]
RP VARIANT MRD59 PRO-292, AND INVOLVEMENT IN MRD59.
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., Gilissen C.,
RA del Rosario M., Hoischen A., Scheffer H., de Vries B.B., Brunner H.G.,
RA 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).
RN [21]
RP VARIANT MRD59 PRO-292, INVOLVEMENT IN MRD59, FUNCTION, AND CHARACTERIZATION
RP OF VARIANT MRD59 PRO-292.
RX PubMed=30184290; DOI=10.1002/humu.23647;
RA Proietti Onori M., Koopal B., Everman D.B., Worthington J.D., Jones J.R.,
RA Ploeg M.A., Mientjes E., van Bon B.W., Kleefstra T., Schulman H.,
RA Kushner S.A., Kuery S., Elgersma Y., van Woerden G.M.;
RT "The intellectual disability-associated CAMK2G p.Arg292Pro mutation acts as
RT a pathogenic gain-of-function.";
RL Hum. Mutat. 39:2008-2024(2018).
CC -!- FUNCTION: Calcium/calmodulin-dependent protein kinase that functions
CC autonomously after Ca(2+)/calmodulin-binding and autophosphorylation,
CC and is involved in sarcoplasmic reticulum Ca(2+) transport in skeletal
CC muscle and may function in dendritic spine and synapse formation and
CC neuronal plasticity. In slow-twitch muscles, is involved in regulation
CC of sarcoplasmic reticulum (SR) Ca(2+) transport and in fast-twitch
CC muscle participates in the control of Ca(2+) release from the SR
CC through phosphorylation of the ryanodine receptor-coupling factor
CC triadin. In the central nervous system, it is involved in the
CC regulation of neurite formation and arborization (PubMed:30184290). It
CC may participate in the promotion of dendritic spine and synapse
CC formation and maintenance of synaptic plasticity which enables long-
CC term potentiation (LTP) and hippocampus-dependent learning.
CC {ECO:0000269|PubMed:16690701, ECO:0000269|PubMed:30184290}.
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. {ECO:0000269|PubMed:14722083}.
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 {ECO:0000269|PubMed:14722083, ECO:0000269|PubMed:20668654}.
CC -!- INTERACTION:
CC Q13555; Q13557: CAMK2D; NbExp=3; IntAct=EBI-1383465, EBI-351018;
CC Q13555; Q13555: CAMK2G; NbExp=2; IntAct=EBI-1383465, EBI-1383465;
CC Q13555; P08238: HSP90AB1; NbExp=2; IntAct=EBI-1383465, EBI-352572;
CC Q13555-5; Q9UQM7: CAMK2A; NbExp=3; IntAct=EBI-12020154, EBI-1383687;
CC Q13555-5; Q13554-3: CAMK2B; NbExp=3; IntAct=EBI-12020154, EBI-11523526;
CC Q13555-5; Q13557-8: CAMK2D; NbExp=3; IntAct=EBI-12020154, EBI-11534483;
CC Q13555-5; Q16543: CDC37; NbExp=3; IntAct=EBI-12020154, EBI-295634;
CC Q13555-5; Q6P1R4: DUS1L; NbExp=3; IntAct=EBI-12020154, EBI-6660325;
CC Q13555-5; P62508-3: ESRRG; NbExp=3; IntAct=EBI-12020154, EBI-12001340;
CC Q13555-5; Q63ZY3: KANK2; NbExp=3; IntAct=EBI-12020154, EBI-2556193;
CC Q13555-5; Q7Z4W3: KRTAP19-3; NbExp=3; IntAct=EBI-12020154, EBI-12020132;
CC Q13555-5; Q3LI64: KRTAP6-1; NbExp=3; IntAct=EBI-12020154, EBI-12111050;
CC Q13555-5; Q9Y3B7: MRPL11; NbExp=3; IntAct=EBI-12020154, EBI-5453723;
CC Q13555-5; P61970: NUTF2; NbExp=3; IntAct=EBI-12020154, EBI-591778;
CC Q13555-5; Q9UBU9: NXF1; NbExp=3; IntAct=EBI-12020154, EBI-398874;
CC Q13555-5; P20618: PSMB1; NbExp=3; IntAct=EBI-12020154, EBI-372273;
CC Q13555-5; Q96SI9: STRBP; NbExp=3; IntAct=EBI-12020154, EBI-740355;
CC Q13555-5; O14787-2: TNPO2; NbExp=3; IntAct=EBI-12020154, EBI-12076664;
CC Q13555-5; Q9Y5L0: TNPO3; NbExp=3; IntAct=EBI-12020154, EBI-1042571;
CC Q13555-5; Q8N0Z6: TTC5; NbExp=3; IntAct=EBI-12020154, EBI-9526213;
CC Q13555-5; Q7KZS0: UBE2I; NbExp=3; IntAct=EBI-12020154, EBI-10180829;
CC -!- SUBCELLULAR LOCATION: 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=11;
CC Name=1;
CC IsoId=Q13555-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q13555-2; Sequence=VSP_013349;
CC Name=3;
CC IsoId=Q13555-3; Sequence=VSP_013350;
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 Name=6;
CC IsoId=Q13555-6; Sequence=VSP_032699, VSP_035456;
CC Name=7; Synonyms=gamma F;
CC IsoId=Q13555-7; Sequence=VSP_013350, VSP_035456;
CC Name=8; Synonyms=gamma E;
CC IsoId=Q13555-8; Sequence=VSP_013349, VSP_035456;
CC Name=9; Synonyms=gamma D;
CC IsoId=Q13555-9; Sequence=VSP_013349, VSP_036027, VSP_035456;
CC Name=10;
CC IsoId=Q13555-10; Sequence=VSP_013350, VSP_004778;
CC Name=11;
CC IsoId=Q13555-11; Sequence=VSP_059393, VSP_013349, VSP_059394;
CC -!- TISSUE SPECIFICITY: Expressed in skeletal muscle.
CC {ECO:0000269|PubMed:16690701}.
CC -!- INDUCTION: Activity is induced in skeletal muscle during exercise.
CC {ECO:0000269|PubMed:16690701}.
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. {ECO:0000269|PubMed:14722083,
CC ECO:0000269|PubMed:16690701}.
CC -!- DISEASE: Intellectual developmental disorder, autosomal dominant 59
CC (MRD59) [MIM:618522]: An autosomal dominant form of intellectual
CC disability, a disorder characterized by significantly below average
CC general intellectual functioning associated with impairments in
CC adaptive behavior and manifested during the developmental period.
CC {ECO:0000269|PubMed:23033978, ECO:0000269|PubMed:30184290}. Note=The
CC disease may be caused by variants affecting the gene represented in
CC this entry.
CC -!- SIMILARITY: Belongs to the protein kinase superfamily. CAMK Ser/Thr
CC protein kinase family. CaMK subfamily. {ECO:0000305}.
CC -!- SEQUENCE CAUTION:
CC Sequence=AAB61379.1; Type=Erroneous initiation; Note=Truncated N-terminus.; Evidence={ECO:0000305};
CC ---------------------------------------------------------------------------
CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms
CC Distributed under the Creative Commons Attribution (CC BY 4.0) License
CC ---------------------------------------------------------------------------
DR EMBL; AC022400; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AL596247; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AL713896; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; KF455257; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CH471083; EAW54527.1; -; 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 CCDS; CCDS73153.1; -. [Q13555-11]
DR CCDS; CCDS7336.1; -. [Q13555-10]
DR CCDS; CCDS7337.1; -. [Q13555-5]
DR CCDS; CCDS7338.1; -. [Q13555-8]
DR PIR; G01975; G01975.
DR PIR; G01978; G01978.
DR RefSeq; NP_001191421.1; NM_001204492.1. [Q13555-11]
DR RefSeq; NP_001213.2; NM_001222.3. [Q13555-10]
DR RefSeq; NP_001307827.1; NM_001320898.1.
DR RefSeq; NP_751909.1; NM_172169.2. [Q13555-5]
DR RefSeq; NP_751913.1; NM_172173.2.
DR RefSeq; XP_005270260.1; XM_005270203.1.
DR PDB; 2UX0; X-ray; 2.46 A; A/B/C/D/E/F=426-558.
DR PDB; 2V7O; X-ray; 2.25 A; A=5-315.
DR PDBsum; 2UX0; -.
DR PDBsum; 2V7O; -.
DR AlphaFoldDB; Q13555; -.
DR SMR; Q13555; -.
DR BioGRID; 107268; 172.
DR DIP; DIP-51315N; -.
DR IntAct; Q13555; 98.
DR MINT; Q13555; -.
DR STRING; 9606.ENSP00000319060; -.
DR BindingDB; Q13555; -.
DR ChEMBL; CHEMBL3829; -.
DR DrugBank; DB08699; 1-tert-butyl-3-(3-methylbenzyl)-1H-pyrazolo[3,4-d]pyrimidin-4-amine.
DR DrugBank; DB06616; Bosutinib.
DR DrugBank; DB12010; Fostamatinib.
DR DrugCentral; Q13555; -.
DR GuidetoPHARMACOLOGY; 1557; -.
DR TCDB; 8.A.104.1.12; the 5'-amp-activated protein kinase (ampk) family.
DR iPTMnet; Q13555; -.
DR PhosphoSitePlus; Q13555; -.
DR BioMuta; CAMK2G; -.
DR DMDM; 62512173; -.
DR EPD; Q13555; -.
DR jPOST; Q13555; -.
DR MassIVE; Q13555; -.
DR MaxQB; Q13555; -.
DR PaxDb; Q13555; -.
DR PeptideAtlas; Q13555; -.
DR PRIDE; Q13555; -.
DR ProteomicsDB; 59538; -. [Q13555-1]
DR ProteomicsDB; 59539; -. [Q13555-10]
DR ProteomicsDB; 59540; -. [Q13555-2]
DR ProteomicsDB; 59541; -. [Q13555-3]
DR ProteomicsDB; 59542; -. [Q13555-4]
DR ProteomicsDB; 59543; -. [Q13555-5]
DR ProteomicsDB; 59544; -. [Q13555-6]
DR ProteomicsDB; 59545; -. [Q13555-7]
DR ProteomicsDB; 59546; -. [Q13555-8]
DR ProteomicsDB; 59547; -. [Q13555-9]
DR Antibodypedia; 29531; 422 antibodies from 35 providers.
DR DNASU; 818; -.
DR Ensembl; ENST00000305762.11; ENSP00000307082.7; ENSG00000148660.21. [Q13555-4]
DR Ensembl; ENST00000322635.7; ENSP00000315599.3; ENSG00000148660.21. [Q13555-5]
DR Ensembl; ENST00000351293.7; ENSP00000277853.5; ENSG00000148660.21. [Q13555-10]
DR Ensembl; ENST00000680035.1; ENSP00000505103.1; ENSG00000148660.21. [Q13555-11]
DR GeneID; 818; -.
DR KEGG; hsa:818; -.
DR UCSC; uc001jvm.2; human. [Q13555-1]
DR UCSC; uc001jvs.2; human.
DR UCSC; uc057uec.1; human.
DR CTD; 818; -.
DR DisGeNET; 818; -.
DR GeneCards; CAMK2G; -.
DR HGNC; HGNC:1463; CAMK2G.
DR HPA; ENSG00000148660; Tissue enhanced (skeletal).
DR MalaCards; CAMK2G; -.
DR MIM; 602123; gene.
DR MIM; 618522; phenotype.
DR neXtProt; NX_Q13555; -.
DR OpenTargets; ENSG00000148660; -.
DR PharmGKB; PA93; -.
DR VEuPathDB; HostDB:ENSG00000148660; -.
DR eggNOG; KOG0033; Eukaryota.
DR GeneTree; ENSGT00940000156481; -.
DR HOGENOM; CLU_000288_71_0_1; -.
DR InParanoid; Q13555; -.
DR OMA; MANPNRE; -.
DR OrthoDB; 330091at2759; -.
DR PhylomeDB; Q13555; -.
DR TreeFam; TF315229; -.
DR BRENDA; 2.7.11.17; 2681.
DR PathwayCommons; Q13555; -.
DR Reactome; R-HSA-111932; CaMK IV-mediated phosphorylation of CREB.
DR Reactome; R-HSA-3371571; HSF1-dependent transactivation.
DR Reactome; R-HSA-399719; Trafficking of AMPA receptors.
DR Reactome; R-HSA-438066; Unblocking of NMDA receptors, glutamate binding and activation.
DR Reactome; R-HSA-442729; CREB1 phosphorylation through the activation of CaMKII/CaMKK/CaMKIV cascasde.
DR Reactome; R-HSA-442982; Ras activation upon Ca2+ influx through NMDA receptor.
DR Reactome; R-HSA-5576892; Phase 0 - rapid depolarisation.
DR Reactome; R-HSA-5578775; Ion homeostasis.
DR Reactome; R-HSA-5673000; RAF activation.
DR Reactome; R-HSA-5673001; RAF/MAP kinase cascade.
DR Reactome; R-HSA-6802946; Signaling by moderate kinase activity BRAF mutants.
DR Reactome; R-HSA-6802952; Signaling by BRAF and RAF1 fusions.
DR Reactome; R-HSA-6802955; Paradoxical activation of RAF signaling by kinase inactive BRAF.
DR Reactome; R-HSA-877300; Interferon gamma signaling.
DR Reactome; R-HSA-9022692; Regulation of MECP2 expression and activity.
DR Reactome; R-HSA-936837; Ion transport by P-type ATPases.
DR Reactome; R-HSA-9609736; Assembly and cell surface presentation of NMDA receptors.
DR Reactome; R-HSA-9617324; Negative regulation of NMDA receptor-mediated neuronal transmission.
DR Reactome; R-HSA-9620244; Long-term potentiation.
DR Reactome; R-HSA-9649948; Signaling downstream of RAS mutants.
DR Reactome; R-HSA-9656223; Signaling by RAF1 mutants.
DR SignaLink; Q13555; -.
DR SIGNOR; Q13555; -.
DR BioGRID-ORCS; 818; 14 hits in 1116 CRISPR screens.
DR ChiTaRS; CAMK2G; human.
DR EvolutionaryTrace; Q13555; -.
DR GeneWiki; CAMK2G; -.
DR GenomeRNAi; 818; -.
DR Pharos; Q13555; Tchem.
DR PRO; PR:Q13555; -.
DR Proteomes; UP000005640; Chromosome 10.
DR RNAct; Q13555; protein.
DR Bgee; ENSG00000148660; Expressed in frontal pole and 191 other tissues.
DR ExpressionAtlas; Q13555; baseline and differential.
DR Genevisible; Q13555; HS.
DR GO; GO:0005954; C:calcium- and calmodulin-dependent protein kinase complex; IDA:BHF-UCL.
DR GO; GO:0005737; C:cytoplasm; IBA:GO_Central.
DR GO; GO:0005829; C:cytosol; TAS:Reactome.
DR GO; GO:0030666; C:endocytic vesicle membrane; TAS:Reactome.
DR GO; GO:0016020; C:membrane; HDA:UniProtKB.
DR GO; GO:0043005; C:neuron projection; IBA:GO_Central.
DR GO; GO:0005654; C:nucleoplasm; TAS:Reactome.
DR GO; GO:0033017; C:sarcoplasmic reticulum membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
DR GO; GO:0004723; F:calcium-dependent protein serine/threonine phosphatase activity; NAS:UniProtKB.
DR GO; GO:0005516; F:calmodulin binding; IBA:GO_Central.
DR GO; GO:0004683; F:calmodulin-dependent protein kinase activity; IBA:GO_Central.
DR GO; GO:0042802; F:identical protein binding; IPI:IntAct.
DR GO; GO:0042803; F:protein homodimerization activity; IPI:BHF-UCL.
DR GO; GO:0106310; F:protein serine kinase activity; IEA:RHEA.
DR GO; GO:0030154; P:cell differentiation; IEA:UniProtKB-KW.
DR GO; GO:0030073; P:insulin secretion; NAS:UniProtKB.
DR GO; GO:0007399; P:nervous system development; IEA:UniProtKB-KW.
DR GO; GO:0006468; P:protein phosphorylation; IEA:InterPro.
DR GO; GO:0051924; P:regulation of calcium ion transport; TAS:UniProtKB.
DR GO; GO:0010975; P:regulation of neuron projection development; IMP:UniProtKB.
DR GO; GO:0014733; P:regulation of skeletal muscle adaptation; TAS:UniProtKB.
DR InterPro; IPR013543; Ca/CaM-dep_prot_kinase-assoc.
DR InterPro; IPR011009; Kinase-like_dom_sf.
DR InterPro; IPR032710; NTF2-like_dom_sf.
DR InterPro; IPR000719; Prot_kinase_dom.
DR InterPro; IPR017441; Protein_kinase_ATP_BS.
DR InterPro; IPR008271; Ser/Thr_kinase_AS.
DR Pfam; PF08332; CaMKII_AD; 1.
DR Pfam; PF00069; Pkinase; 1.
DR SMART; SM00220; S_TKc; 1.
DR SUPFAM; SSF54427; SSF54427; 1.
DR SUPFAM; SSF56112; SSF56112; 1.
DR PROSITE; PS00107; PROTEIN_KINASE_ATP; 1.
DR PROSITE; PS50011; PROTEIN_KINASE_DOM; 1.
DR PROSITE; PS00108; PROTEIN_KINASE_ST; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Alternative splicing; ATP-binding; Calmodulin-binding;
KW Developmental protein; Differentiation; Intellectual disability; Kinase;
KW Membrane; Neurogenesis; Nucleotide-binding; Phosphoprotein;
KW Reference proteome; Sarcoplasmic reticulum;
KW Serine/threonine-protein kinase; Transferase.
FT CHAIN 1..558
FT /note="Calcium/calmodulin-dependent protein kinase type II
FT subunit gamma"
FT /id="PRO_0000086101"
FT DOMAIN 14..272
FT /note="Protein kinase"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT REGION 283..292
FT /note="Autoinhibitory domain"
FT REGION 291..301
FT /note="Calmodulin-binding"
FT /evidence="ECO:0000250"
FT REGION 294..316
FT /note="Calmodulin-binding"
FT REGION 324..353
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 376..423
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 336..353
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 386..404
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 408..423
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
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 287
FT /note="Phosphothreonine; by autocatalysis"
FT /evidence="ECO:0000269|PubMed:16690701,
FT ECO:0007744|PubMed:19369195, ECO:0007744|PubMed:23186163"
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:0000305"
FT MOD_RES 311
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:18691976,
FT ECO:0007744|PubMed:19369195, ECO:0007744|PubMed:20068231"
FT MOD_RES 334
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P11730"
FT MOD_RES 349
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:18691976"
FT MOD_RES 352
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:18691976,
FT ECO:0007744|PubMed:19369195"
FT MOD_RES 419
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:18691976,
FT ECO:0007744|PubMed:19369195, ECO:0007744|PubMed:23186163,
FT ECO:0007744|PubMed:24275569"
FT MOD_RES 484
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P11730"
FT VAR_SEQ 315
FT /note="S -> SVGRQSSAPASPAASAAGLAGQ (in isoform 5 and
FT isoform 6)"
FT /evidence="ECO:0000303|PubMed:15489334"
FT /id="VSP_032699"
FT VAR_SEQ 316
FT /note="A -> VGRQSSAPASPAASAAGLAGQA (in isoform 11)"
FT /id="VSP_059393"
FT VAR_SEQ 331..364
FT /note="Missing (in isoform 3, isoform 7 and isoform 10)"
FT /evidence="ECO:0000303|PubMed:7557101,
FT ECO:0000303|PubMed:8449910"
FT /id="VSP_013350"
FT VAR_SEQ 331..341
FT /note="Missing (in isoform 2, isoform 8, isoform 9 and
FT isoform 11)"
FT /evidence="ECO:0000303|PubMed:7557101,
FT ECO:0000303|PubMed:9060999"
FT /id="VSP_013349"
FT VAR_SEQ 341..363
FT /note="Missing (in isoform 5)"
FT /evidence="ECO:0000303|PubMed:15489334"
FT /id="VSP_032700"
FT VAR_SEQ 351..364
FT /note="Missing (in isoform 9)"
FT /evidence="ECO:0000303|PubMed:7557101"
FT /id="VSP_036027"
FT VAR_SEQ 396..426
FT /note="GRVPEGRSSRDRTAPSAGMQPQPSLCSSAMR -> VR (in isoform
FT 11)"
FT /id="VSP_059394"
FT VAR_SEQ 396..425
FT /note="GRVPEGRSSRDRTAPSAGMQPQPSLCSSAM -> V (in isoform 4,
FT isoform 5 and isoform 10)"
FT /evidence="ECO:0000303|PubMed:15489334,
FT ECO:0000303|PubMed:8449910, ECO:0000303|PubMed:9060999"
FT /id="VSP_004778"
FT VAR_SEQ 397..398
FT /note="RV -> APLRTGNGSSV (in isoform 6, isoform 7, isoform
FT 8 and isoform 9)"
FT /evidence="ECO:0000303|PubMed:7557101"
FT /id="VSP_035456"
FT VARIANT 36
FT /note="S -> P (in dbSNP:rs17853266)"
FT /evidence="ECO:0000269|PubMed:15489334, ECO:0000269|Ref.2"
FT /id="VAR_042430"
FT VARIANT 292
FT /note="R -> P (in MRD59; gain-of-function variant affecting
FT regulation of neurite formation and arborization; results
FT in constitutive autophosphorylation; dbSNP:rs397514627)"
FT /evidence="ECO:0000269|PubMed:23033978,
FT ECO:0000269|PubMed:30184290"
FT /id="VAR_069390"
FT CONFLICT 230
FT /note="A -> T (in Ref. 6; AAB61379)"
FT /evidence="ECO:0000305"
FT HELIX 9..13
FT /evidence="ECO:0007829|PDB:2V7O"
FT STRAND 14..22
FT /evidence="ECO:0007829|PDB:2V7O"
FT STRAND 26..33
FT /evidence="ECO:0007829|PDB:2V7O"
FT TURN 34..37
FT /evidence="ECO:0007829|PDB:2V7O"
FT STRAND 38..46
FT /evidence="ECO:0007829|PDB:2V7O"
FT HELIX 52..67
FT /evidence="ECO:0007829|PDB:2V7O"
FT STRAND 76..81
FT /evidence="ECO:0007829|PDB:2V7O"
FT STRAND 83..91
FT /evidence="ECO:0007829|PDB:2V7O"
FT HELIX 98..103
FT /evidence="ECO:0007829|PDB:2V7O"
FT HELIX 110..129
FT /evidence="ECO:0007829|PDB:2V7O"
FT HELIX 139..141
FT /evidence="ECO:0007829|PDB:2V7O"
FT STRAND 142..145
FT /evidence="ECO:0007829|PDB:2V7O"
FT STRAND 153..155
FT /evidence="ECO:0007829|PDB:2V7O"
FT HELIX 178..180
FT /evidence="ECO:0007829|PDB:2V7O"
FT HELIX 183..187
FT /evidence="ECO:0007829|PDB:2V7O"
FT HELIX 194..209
FT /evidence="ECO:0007829|PDB:2V7O"
FT HELIX 219..227
FT /evidence="ECO:0007829|PDB:2V7O"
FT HELIX 237..240
FT /evidence="ECO:0007829|PDB:2V7O"
FT HELIX 243..252
FT /evidence="ECO:0007829|PDB:2V7O"
FT TURN 257..259
FT /evidence="ECO:0007829|PDB:2V7O"
FT HELIX 263..266
FT /evidence="ECO:0007829|PDB:2V7O"
FT HELIX 270..273
FT /evidence="ECO:0007829|PDB:2V7O"
FT HELIX 275..278
FT /evidence="ECO:0007829|PDB:2V7O"
FT HELIX 285..301
FT /evidence="ECO:0007829|PDB:2V7O"
FT HELIX 425..443
FT /evidence="ECO:0007829|PDB:2UX0"
FT HELIX 446..452
FT /evidence="ECO:0007829|PDB:2UX0"
FT STRAND 453..460
FT /evidence="ECO:0007829|PDB:2UX0"
FT HELIX 462..464
FT /evidence="ECO:0007829|PDB:2UX0"
FT STRAND 468..470
FT /evidence="ECO:0007829|PDB:2UX0"
FT HELIX 471..481
FT /evidence="ECO:0007829|PDB:2UX0"
FT TURN 482..485
FT /evidence="ECO:0007829|PDB:2UX0"
FT STRAND 490..501
FT /evidence="ECO:0007829|PDB:2UX0"
FT STRAND 506..518
FT /evidence="ECO:0007829|PDB:2UX0"
FT STRAND 524..538
FT /evidence="ECO:0007829|PDB:2UX0"
FT STRAND 541..550
FT /evidence="ECO:0007829|PDB:2UX0"
FT MOD_RES Q13555-2:325
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:18691976,
FT ECO:0007744|PubMed:19369195"
FT MOD_RES Q13555-3:325
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:18691976,
FT ECO:0007744|PubMed:19369195"
FT MOD_RES Q13555-5:325
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:18691976"
FT MOD_RES Q13555-6:325
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:18691976"
FT MOD_RES Q13555-7:325
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:18691976,
FT ECO:0007744|PubMed:19369195"
FT MOD_RES Q13555-8:325
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:18691976,
FT ECO:0007744|PubMed:19369195"
FT MOD_RES Q13555-9:325
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:18691976,
FT ECO:0007744|PubMed:19369195"
FT MOD_RES Q13555-9:338
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:18691976"
FT MOD_RES Q13555-10:325
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:18691976,
FT ECO:0007744|PubMed:19369195"
FT MOD_RES Q13555-11:325
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:18691976"
FT MOD_RES Q13555-11:346
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:18691976,
FT ECO:0007744|PubMed:19369195"
SQ SEQUENCE 558 AA; 62607 MW; 7D61AB799B8F8CEB 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 DEDLKGRVPE GRSSRDRTAP SAGMQPQPSL
CSSAMRKQEI IKITEQLIEA INNGDFEAYT KICDPGLTSF EPEALGNLVE GMDFHKFYFE
NLLSKNSKPI HTTILNPHVH VIGEDAACIA YIRLTQYIDG QGRPRTSQSE ETRVWHRRDG
KWLNVHYHCS GAPAAPLQ
