KCC2G_RAT
ID KCC2G_RAT Reviewed; 527 AA.
AC P11730; Q64003; Q64004;
DT 01-OCT-1989, integrated into UniProtKB/Swiss-Prot.
DT 01-OCT-1989, sequence version 1.
DT 03-AUG-2022, entry version 181.
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 Rattus norvegicus (Rat).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Rattus.
OX NCBI_TaxID=10116;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM A).
RC TISSUE=Brain;
RX PubMed=2846534; DOI=10.1016/s0021-9258(18)37561-6;
RA Tobimatsu T., Kameshita I., Fujisawa H.;
RT "Molecular cloning of the cDNA encoding the third polypeptide (gamma) of
RT brain calmodulin-dependent protein kinase II.";
RL J. Biol. Chem. 263:16082-16086(1988).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS B AND C).
RC TISSUE=Aortic smooth muscle;
RX PubMed=8172610; DOI=10.1042/bj2990489;
RA Zhou Z.L., Ikebe M.;
RT "New isoforms of Ca2+/calmodulin-dependent protein kinase II in smooth
RT muscle.";
RL Biochem. J. 299:489-495(1994).
RN [3]
RP INDUCTION BY COCAINE.
RX PubMed=16891908; DOI=10.1097/01.fjc.0000211796.45281.46;
RA Henning R.J., Cuevas J.;
RT "Cocaine activates calcium/calmodulin kinase II and causes cardiomyocyte
RT hypertrophy.";
RL J. Cardiovasc. Pharmacol. 48:802-813(2006).
RN [4]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-311; SER-321; SER-325;
RP SER-329; SER-355 AND SER-453, AND IDENTIFICATION BY MASS SPECTROMETRY
RP [LARGE SCALE ANALYSIS].
RX PubMed=22673903; DOI=10.1038/ncomms1871;
RA Lundby A., Secher A., Lage K., Nordsborg N.B., Dmytriyev A., Lundby C.,
RA Olsen J.V.;
RT "Quantitative maps of protein phosphorylation sites across 14 different rat
RT organs and tissues.";
RL Nat. Commun. 3:876-876(2012).
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. It may participate in
CC the promotion of dendritic spine and synapse formation and maintenance
CC of synaptic plasticity which enables long-term potentiation (LTP) and
CC hippocampus-dependent learning (By similarity).
CC {ECO:0000250|UniProtKB:Q923T9}.
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=A;
CC IsoId=P11730-1; Sequence=Displayed;
CC Name=B;
CC IsoId=P11730-2; Sequence=VSP_004781, VSP_004782;
CC Name=C;
CC IsoId=P11730-3; Sequence=VSP_004781, VSP_004783;
CC -!- INDUCTION: By cocaine in cardiomyocytes. {ECO:0000269|PubMed:16891908}.
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; J04063; AAA41857.1; -; mRNA.
DR EMBL; S71570; AAB30670.1; -; mRNA.
DR EMBL; S71571; AAB30671.1; -; mRNA.
DR PIR; A31908; A31908.
DR PIR; S43845; S43845.
DR RefSeq; NP_598289.1; NM_133605.1. [P11730-1]
DR RefSeq; XP_008768721.1; XM_008770499.2. [P11730-3]
DR AlphaFoldDB; P11730; -.
DR SMR; P11730; -.
DR BioGRID; 251145; 9.
DR IntAct; P11730; 3.
DR MINT; P11730; -.
DR STRING; 10116.ENSRNOP00000062321; -.
DR BindingDB; P11730; -.
DR ChEMBL; CHEMBL5109; -.
DR iPTMnet; P11730; -.
DR PhosphoSitePlus; P11730; -.
DR jPOST; P11730; -.
DR PaxDb; P11730; -.
DR PRIDE; P11730; -.
DR Ensembl; ENSRNOT00000066163; ENSRNOP00000062321; ENSRNOG00000009783. [P11730-1]
DR GeneID; 171140; -.
DR KEGG; rno:171140; -.
DR UCSC; RGD:621802; rat. [P11730-1]
DR CTD; 818; -.
DR RGD; 621802; Camk2g.
DR eggNOG; KOG0033; Eukaryota.
DR GeneTree; ENSGT00940000156481; -.
DR HOGENOM; CLU_000288_71_3_1; -.
DR InParanoid; P11730; -.
DR OMA; MANPNRE; -.
DR OrthoDB; 330091at2759; -.
DR PhylomeDB; P11730; -.
DR BRENDA; 2.7.11.17; 5301.
DR Reactome; R-RNO-3371571; HSF1-dependent transactivation.
DR Reactome; R-RNO-438066; Unblocking of NMDA receptors, glutamate binding and activation.
DR Reactome; R-RNO-5576892; Phase 0 - rapid depolarisation.
DR Reactome; R-RNO-5578775; Ion homeostasis.
DR Reactome; R-RNO-5673000; RAF activation.
DR Reactome; R-RNO-5673001; RAF/MAP kinase cascade.
DR Reactome; R-RNO-877300; Interferon gamma signaling.
DR Reactome; R-RNO-936837; Ion transport by P-type ATPases.
DR PRO; PR:P11730; -.
DR Proteomes; UP000002494; Chromosome 15.
DR Bgee; ENSRNOG00000009783; Expressed in frontal cortex and 19 other tissues.
DR ExpressionAtlas; P11730; baseline and differential.
DR Genevisible; P11730; RN.
DR GO; GO:0005954; C:calcium- and calmodulin-dependent protein kinase complex; ISO:RGD.
DR GO; GO:0005737; C:cytoplasm; IBA:GO_Central.
DR GO; GO:0005829; C:cytosol; TAS:Reactome.
DR GO; GO:0043005; C:neuron projection; IBA:GO_Central.
DR GO; GO:0005654; C:nucleoplasm; TAS:Reactome.
DR GO; GO:0014069; C:postsynaptic density; ISO:RGD.
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; IDA:RGD.
DR GO; GO:0042802; F:identical protein binding; ISO:RGD.
DR GO; GO:0042803; F:protein homodimerization activity; ISO:RGD.
DR GO; GO:0106310; F:protein serine kinase activity; IEA:RHEA.
DR GO; GO:0004674; F:protein serine/threonine kinase activity; ISO:RGD.
DR GO; GO:0006816; P:calcium ion transport; ISO:RGD.
DR GO; GO:0030154; P:cell differentiation; IEA:UniProtKB-KW.
DR GO; GO:0000082; P:G1/S transition of mitotic cell cycle; ISO:RGD.
DR GO; GO:0007399; P:nervous system development; IEA:UniProtKB-KW.
DR GO; GO:0046777; P:protein autophosphorylation; IDA:RGD.
DR GO; GO:0048169; P:regulation of long-term neuronal synaptic plasticity; TAS:RGD.
DR GO; GO:0010975; P:regulation of neuron projection development; ISO:RGD.
DR GO; GO:1903076; P:regulation of protein localization to plasma membrane; IGI:ARUK-UCL.
DR GO; GO:1901897; P:regulation of relaxation of cardiac muscle; ISO:RGD.
DR GO; GO:0001666; P:response to hypoxia; IDA:RGD.
DR GO; GO:0006979; P:response to oxidative stress; IDA:RGD.
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..527
FT /note="Calcium/calmodulin-dependent protein kinase type II
FT subunit gamma"
FT /id="PRO_0000086103"
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 344..389
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 359..383
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:0000250|UniProtKB:Q13555"
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:22673903"
FT MOD_RES 321
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:22673903"
FT MOD_RES 325
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:22673903"
FT MOD_RES 329
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:22673903"
FT MOD_RES 355
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:22673903"
FT MOD_RES 453
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:22673903"
FT VAR_SEQ 316..336
FT /note="Missing (in isoform B and isoform C)"
FT /evidence="ECO:0000303|PubMed:8172610"
FT /id="VSP_004781"
FT VAR_SEQ 351..361
FT /note="KKRKSSSSVHL -> PEQQQKQSRKPSPRARDPLQTA (in isoform
FT B)"
FT /evidence="ECO:0000303|PubMed:8172610"
FT /id="VSP_004782"
FT VAR_SEQ 352..362
FT /note="Missing (in isoform C)"
FT /evidence="ECO:0000303|PubMed:8172610"
FT /id="VSP_004783"
FT CONFLICT 2
FT /note="A -> E (in Ref. 2; AAB30670/AAB30671)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 527 AA; 59038 MW; 58DBF1B72F64FA31 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 SRNFSVGRQS SAPASPAASA AGLAGQAAKS LLNKKSDGGV KKRKSSSSVH
LMEPQTTVVH NATDGIKGST ESCNTTTEDE DLKVRKQEII KITEQLIEAI NNGDFEAYTK
ICDPGLTSFE PEALGNLVEG MDFHKFYFEN LLSKNSKPIH TTILNPHVHV IGEDAACIAY
IRLTQYIDGQ GRPRTSQSEE TRVWHRRDGK WLNVHYHCSG APAAPLQ
