KCC2G_MOUSE
ID KCC2G_MOUSE Reviewed; 529 AA.
AC Q923T9; Q3U3H3; Q8VED3;
DT 16-APR-2002, integrated into UniProtKB/Swiss-Prot.
DT 01-DEC-2001, sequence version 1.
DT 03-AUG-2022, entry version 192.
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;
OS Mus musculus (Mouse).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Mus; Mus.
OX NCBI_TaxID=10090;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
RC STRAIN=C57BL/6J;
RA Szendro P.I., Cadenas C., Eichele G.;
RT "Identification of a mouse Ca2+/calmodulin-dependent protein kinase II.";
RL Submitted (JUN-2001) to the EMBL/GenBank/DDBJ databases.
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2).
RC STRAIN=NOD; TISSUE=Dendritic cell;
RX PubMed=16141072; DOI=10.1126/science.1112014;
RA Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N.,
RA Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K.,
RA Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J.,
RA Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R.,
RA Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T.,
RA Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A.,
RA Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B.,
RA Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M.,
RA Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S.,
RA Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E.,
RA Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D.,
RA Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M.,
RA Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H.,
RA Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V.,
RA Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S.,
RA Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H.,
RA Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N.,
RA Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F.,
RA Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G.,
RA Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z.,
RA Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C.,
RA Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y.,
RA Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S.,
RA Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K.,
RA Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R.,
RA van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H.,
RA Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M.,
RA Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C.,
RA Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S.,
RA Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K.,
RA Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M.,
RA Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C.,
RA Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A.,
RA Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y.;
RT "The transcriptional landscape of the mammalian genome.";
RL Science 309:1559-1563(2005).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 2 AND 3).
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 PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-287, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Brain;
RX PubMed=16452087; DOI=10.1074/mcp.t500041-mcp200;
RA Trinidad J.C., Specht C.G., Thalhammer A., Schoepfer R., Burlingame A.L.;
RT "Comprehensive identification of phosphorylation sites in postsynaptic
RT density preparations.";
RL Mol. Cell. Proteomics 5:914-922(2006).
RN [5]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Brain cortex;
RX PubMed=17114649; DOI=10.1074/mcp.m600046-mcp200;
RA Munton R.P., Tweedie-Cullen R., Livingstone-Zatchej M., Weinandy F.,
RA Waidelich M., Longo D., Gehrig P., Potthast F., Rutishauser D., Gerrits B.,
RA Panse C., Schlapbach R., Mansuy I.M.;
RT "Qualitative and quantitative analyses of protein phosphorylation in naive
RT and stimulated mouse synaptosomal preparations.";
RL Mol. Cell. Proteomics 6:283-293(2007).
RN [6]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-311, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Brain, Heart, Kidney, and Spleen;
RX PubMed=21183079; DOI=10.1016/j.cell.2010.12.001;
RA Huttlin E.L., Jedrychowski M.P., Elias J.E., Goswami T., Rad R.,
RA Beausoleil S.A., Villen J., Haas W., Sowa M.E., Gygi S.P.;
RT "A tissue-specific atlas of mouse protein phosphorylation and expression.";
RL Cell 143:1174-1189(2010).
RN [7]
RP FUNCTION.
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 (By
CC similarity) (PubMed:30184290). {ECO:0000250,
CC 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.
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 (By
CC similarity). {ECO:0000250}.
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=3;
CC Comment=Additional isoforms seem to exist.;
CC Name=1;
CC IsoId=Q923T9-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q923T9-2; Sequence=VSP_004779;
CC Name=3;
CC IsoId=Q923T9-3; Sequence=VSP_004780;
CC -!- DOMAIN: The CAMK2 protein kinases contain a unique C-terminal subunit
CC association domain responsible for oligomerization.
CC -!- PTM: Autophosphorylation of Thr-287 following activation by
CC Ca(2+)/calmodulin. Phosphorylation of Thr-287 locks the kinase into an
CC activated state (By similarity). {ECO:0000250}.
CC -!- SIMILARITY: Belongs to the protein kinase superfamily. CAMK Ser/Thr
CC protein kinase family. CaMK subfamily. {ECO:0000305}.
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DR EMBL; AF395884; AAK84142.1; -; mRNA.
DR EMBL; AK154764; BAE32813.1; -; mRNA.
DR EMBL; BC019162; AAH19162.1; -; mRNA.
DR EMBL; BC025597; AAH25597.1; -; mRNA.
DR CCDS; CCDS26855.1; -. [Q923T9-2]
DR CCDS; CCDS26856.1; -. [Q923T9-3]
DR CCDS; CCDS26857.1; -. [Q923T9-1]
DR RefSeq; NP_001034227.1; NM_001039138.2. [Q923T9-2]
DR RefSeq; NP_001034228.1; NM_001039139.2. [Q923T9-3]
DR RefSeq; NP_848712.2; NM_178597.5. [Q923T9-1]
DR AlphaFoldDB; Q923T9; -.
DR SMR; Q923T9; -.
DR BioGRID; 198463; 22.
DR IntAct; Q923T9; 11.
DR MINT; Q923T9; -.
DR STRING; 10090.ENSMUSP00000071720; -.
DR iPTMnet; Q923T9; -.
DR PhosphoSitePlus; Q923T9; -.
DR SwissPalm; Q923T9; -.
DR EPD; Q923T9; -.
DR jPOST; Q923T9; -.
DR MaxQB; Q923T9; -.
DR PaxDb; Q923T9; -.
DR PeptideAtlas; Q923T9; -.
DR PRIDE; Q923T9; -.
DR ProteomicsDB; 269183; -. [Q923T9-1]
DR ProteomicsDB; 269184; -. [Q923T9-2]
DR ProteomicsDB; 269185; -. [Q923T9-3]
DR Antibodypedia; 29531; 422 antibodies from 35 providers.
DR DNASU; 12325; -.
DR Ensembl; ENSMUST00000071816; ENSMUSP00000071720; ENSMUSG00000021820. [Q923T9-1]
DR Ensembl; ENSMUST00000080440; ENSMUSP00000079298; ENSMUSG00000021820. [Q923T9-2]
DR Ensembl; ENSMUST00000100837; ENSMUSP00000098398; ENSMUSG00000021820. [Q923T9-3]
DR GeneID; 12325; -.
DR KEGG; mmu:12325; -.
DR UCSC; uc007skt.2; mouse. [Q923T9-1]
DR UCSC; uc007sku.2; mouse. [Q923T9-2]
DR CTD; 818; -.
DR MGI; MGI:88259; Camk2g.
DR VEuPathDB; HostDB:ENSMUSG00000021820; -.
DR eggNOG; KOG0033; Eukaryota.
DR GeneTree; ENSGT00940000156481; -.
DR HOGENOM; CLU_000288_71_0_1; -.
DR InParanoid; Q923T9; -.
DR OrthoDB; 330091at2759; -.
DR PhylomeDB; Q923T9; -.
DR TreeFam; TF315229; -.
DR BRENDA; 2.7.11.17; 3474.
DR Reactome; R-MMU-3371571; HSF1-dependent transactivation.
DR Reactome; R-MMU-438066; Unblocking of NMDA receptors, glutamate binding and activation.
DR Reactome; R-MMU-5576892; Phase 0 - rapid depolarisation.
DR Reactome; R-MMU-5578775; Ion homeostasis.
DR Reactome; R-MMU-5673000; RAF activation.
DR Reactome; R-MMU-5673001; RAF/MAP kinase cascade.
DR Reactome; R-MMU-877300; Interferon gamma signaling.
DR Reactome; R-MMU-936837; Ion transport by P-type ATPases.
DR BioGRID-ORCS; 12325; 2 hits in 76 CRISPR screens.
DR ChiTaRS; Camk2g; mouse.
DR PRO; PR:Q923T9; -.
DR Proteomes; UP000000589; Chromosome 14.
DR RNAct; Q923T9; protein.
DR Bgee; ENSMUSG00000021820; Expressed in animal zygote and 234 other tissues.
DR ExpressionAtlas; Q923T9; baseline and differential.
DR Genevisible; Q923T9; MM.
DR GO; GO:0005954; C:calcium- and calmodulin-dependent protein kinase complex; ISO:MGI.
DR GO; GO:0005737; C:cytoplasm; IBA:GO_Central.
DR GO; GO:0043005; C:neuron projection; IBA:GO_Central.
DR GO; GO:0014069; C:postsynaptic density; IDA:MGI.
DR GO; GO:0033017; C:sarcoplasmic reticulum membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
DR GO; GO:0005516; F:calmodulin binding; IBA:GO_Central.
DR GO; GO:0004683; F:calmodulin-dependent protein kinase activity; ISO:MGI.
DR GO; GO:0042802; F:identical protein binding; ISO:MGI.
DR GO; GO:0042803; F:protein homodimerization activity; ISO:MGI.
DR GO; GO:0106310; F:protein serine kinase activity; IEA:RHEA.
DR GO; GO:0004674; F:protein serine/threonine kinase activity; IMP:MGI.
DR GO; GO:0006816; P:calcium ion transport; IMP:MGI.
DR GO; GO:0030154; P:cell differentiation; IEA:UniProtKB-KW.
DR GO; GO:0000082; P:G1/S transition of mitotic cell cycle; IMP:MGI.
DR GO; GO:0007399; P:nervous system development; IEA:UniProtKB-KW.
DR GO; GO:0046777; P:protein autophosphorylation; IMP:MGI.
DR GO; GO:0010975; P:regulation of neuron projection development; IMP:UniProtKB.
DR GO; GO:1903076; P:regulation of protein localization to plasma membrane; ISO:MGI.
DR GO; GO:1901897; P:regulation of relaxation of cardiac muscle; IGI:BHF-UCL.
DR GO; GO:0001666; P:response to hypoxia; ISO:MGI.
DR GO; GO:0006979; P:response to oxidative stress; ISO:MGI.
DR InterPro; IPR013543; Ca/CaM-dep_prot_kinase-assoc.
DR InterPro; IPR011009; Kinase-like_dom_sf.
DR InterPro; IPR032710; NTF2-like_dom_sf.
DR InterPro; IPR000719; Prot_kinase_dom.
DR InterPro; IPR017441; Protein_kinase_ATP_BS.
DR InterPro; IPR008271; Ser/Thr_kinase_AS.
DR Pfam; PF08332; CaMKII_AD; 1.
DR Pfam; PF00069; Pkinase; 1.
DR SMART; SM00220; S_TKc; 1.
DR SUPFAM; SSF54427; SSF54427; 1.
DR SUPFAM; SSF56112; SSF56112; 1.
DR PROSITE; PS00107; PROTEIN_KINASE_ATP; 1.
DR PROSITE; PS50011; PROTEIN_KINASE_DOM; 1.
DR PROSITE; PS00108; PROTEIN_KINASE_ST; 1.
PE 1: Evidence at protein level;
KW Alternative splicing; ATP-binding; Calmodulin-binding;
KW Developmental protein; Differentiation; Kinase; Membrane; Neurogenesis;
KW Nucleotide-binding; Phosphoprotein; Reference proteome;
KW Sarcoplasmic reticulum; Serine/threonine-protein kinase; Transferase.
FT CHAIN 1..529
FT /note="Calcium/calmodulin-dependent protein kinase type II
FT subunit gamma"
FT /id="PRO_0000086102"
FT DOMAIN 14..272
FT /note="Protein kinase"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT REGION 283..292
FT /note="Autoinhibitory domain"
FT /evidence="ECO:0000250"
FT REGION 291..301
FT /note="Calmodulin-binding"
FT /evidence="ECO:0000250"
FT REGION 324..353
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 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:0007744|PubMed:16452087"
FT MOD_RES 306
FT /note="Phosphothreonine; by autocatalysis"
FT /evidence="ECO:0000250"
FT MOD_RES 307
FT /note="Phosphothreonine; by autocatalysis"
FT /evidence="ECO:0000250"
FT MOD_RES 311
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:21183079"
FT MOD_RES 334
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P11730"
FT MOD_RES 349
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q13555"
FT MOD_RES 352
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q13555"
FT MOD_RES 455
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P11730"
FT VAR_SEQ 331..364
FT /note="Missing (in isoform 3)"
FT /evidence="ECO:0000303|PubMed:15489334"
FT /id="VSP_004780"
FT VAR_SEQ 331..341
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:15489334,
FT ECO:0000303|PubMed:16141072"
FT /id="VSP_004779"
SQ SEQUENCE 529 AA; 59607 MW; EE1D127BBA178544 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 DEDLKVRKQE IIKITEQLIE AINNGDFEAY
TKICDPGLTS FEPEALGNLV EGMDFHKFYF ENLLSKNSKP IHTTILNPHV HVIGEDAACI
AYIRLTQYID GQGRPRTSQS EETRVWHRRD GKWLNVHYHC SGAPAAPLQ
