KCC2B_RAT
ID KCC2B_RAT Reviewed; 542 AA.
AC P08413;
DT 01-AUG-1988, integrated into UniProtKB/Swiss-Prot.
DT 01-AUG-1988, sequence version 1.
DT 03-AUG-2022, entry version 186.
DE RecName: Full=Calcium/calmodulin-dependent protein kinase type II subunit beta;
DE Short=CaM kinase II subunit beta;
DE Short=CaMK-II subunit beta;
DE EC=2.7.11.17;
GN Name=Camk2b;
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].
RC TISSUE=Brain;
RX PubMed=3470758; DOI=10.1073/pnas.84.7.1794;
RA Bennett M.K., Kennedy M.B.;
RT "Deduced primary structure of the beta subunit of brain type II
RT Ca2+/calmodulin-dependent protein kinase determined by molecular cloning.";
RL Proc. Natl. Acad. Sci. U.S.A. 84:1794-1798(1987).
RN [2]
RP SUBCELLULAR LOCATION, AND TISSUE SPECIFICITY.
RX PubMed=9768845; DOI=10.1016/s0896-6273(00)80569-3;
RA Shen K., Teruel M.N., Subramanian K., Meyer T.;
RT "CaMKIIbeta functions as an F-actin targeting module that localizes
RT CaMKIIalpha/beta heterooligomers to dendritic spines.";
RL Neuron 21:593-606(1998).
RN [3]
RP INTERACTION WITH CAMK2N2.
RX PubMed=9724800; DOI=10.1073/pnas.95.18.10890;
RA Chang B.H., Mukherji S., Soderling T.R.;
RT "Characterization of a calmodulin kinase II inhibitor protein in brain.";
RL Proc. Natl. Acad. Sci. U.S.A. 95:10890-10895(1998).
RN [4]
RP INTERACTION WITH CAMK2N1.
RX PubMed=11182241; DOI=10.1016/s0306-4522(00)00520-0;
RA Chang B.H., Mukherji S., Soderling T.R.;
RT "Calcium/calmodulin-dependent protein kinase II inhibitor protein:
RT localization of isoforms in rat brain.";
RL Neuroscience 102:767-777(2001).
RN [5]
RP FUNCTION IN SYNAPSE FORMATION, SUBCELLULAR LOCATION, AND MUTAGENESIS OF
RP LYS-43; THR-287 AND ALA-303.
RX PubMed=12873385; DOI=10.1016/s0896-6273(03)00428-8;
RA Fink C.C., Bayer K.U., Myers J.W., Ferrell J.E. Jr., Schulman H., Meyer T.;
RT "Selective regulation of neurite extension and synapse formation by the
RT beta but not the alpha isoform of CaMKII.";
RL Neuron 39:283-297(2003).
RN [6]
RP INTERACTION WITH SYNGAP1 AND MPDZ, AND FUNCTION.
RX PubMed=15312654; DOI=10.1016/j.neuron.2004.08.003;
RA Krapivinsky G., Medina I., Krapivinsky L., Gapon S., Clapham D.E.;
RT "SynGAP-MUPP1-CaMKII synaptic complexes regulate p38 MAP kinase activity
RT and NMDA receptor-dependent synaptic AMPA receptor potentiation.";
RL Neuron 43:563-574(2004).
RN [7]
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 [8]
RP FUNCTION, INDUCTION, AND PHOSPHORYLATION AT THR-287.
RX PubMed=17272343; DOI=10.1113/jphysiol.2006.127464;
RA Rose A.J., Alsted T.J., Kobberoe J.B., Richter E.A.;
RT "Regulation and function of Ca2+-calmodulin-dependent protein kinase II of
RT fast-twitch rat skeletal muscle.";
RL J. Physiol. (Lond.) 580:993-1005(2007).
RN [9]
RP SUBCELLULAR LOCATION, AND INTERACTION WITH ARC.
RX PubMed=22579289; DOI=10.1016/j.cell.2012.02.062;
RA Okuno H., Akashi K., Ishii Y., Yagishita-Kyo N., Suzuki K., Nonaka M.,
RA Kawashima T., Fujii H., Takemoto-Kimura S., Abe M., Natsume R.,
RA Chowdhury S., Sakimura K., Worley P.F., Bito H.;
RT "Inverse synaptic tagging of inactive synapses via dynamic interaction of
RT Arc/Arg3.1 with CaMKIIbeta.";
RL Cell 149:886-898(2012).
RN [10]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-367; SER-394; SER-397 AND
RP THR-401, AND IDENTIFICATION BY MASS SPECTROMETRY [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 dendritic spine and synapse formation, neuronal
CC plasticity and regulation of sarcoplasmic reticulum Ca(2+) transport in
CC skeletal muscle. In neurons, plays an essential structural role in the
CC reorganization of the actin cytoskeleton during plasticity by binding
CC and bundling actin filaments in a kinase-independent manner. This
CC structural function is required for correct targeting of CaMK2A, which
CC acts downstream of NMDAR to promote dendritic spine and synapse
CC formation and maintain synaptic plasticity which enables long-term
CC potentiation (LTP) and hippocampus-dependent learning. In developing
CC hippocampal neurons, promotes arborization of the dendritic tree and in
CC mature neurons, promotes dendritic remodeling. Also regulates the
CC migration of developing neurons. Participates in the modulation of
CC skeletal muscle function in response to exercise. In slow-twitch
CC muscles, is involved in regulation of sarcoplasmic reticulum (SR)
CC Ca(2+) transport and in fast-twitch muscle participates in the control
CC of Ca(2+) release from the SR through phosphorylation of triadin, a
CC ryanodine receptor-coupling factor, and phospholamban (PLN/PLB), an
CC endogenous inhibitor of SERCA2A/ATP2A2. {ECO:0000250|UniProtKB:Q13554,
CC ECO:0000269|PubMed:12873385, ECO:0000269|PubMed:15312654,
CC ECO:0000269|PubMed:17272343}.
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). Interacts with SYNGAP1, CAMK2N2 and MPDZ (PubMed:9724800,
CC PubMed:15312654). Interacts with FOXO3 (By similarity). Interacts (when
CC in a kinase inactive state not associated with calmodulin) with ARC;
CC leading to target ARC to inactive synapses (PubMed:22579289). Interacts
CC with CAMK2N1; this interaction requires CAMK2B activation by Ca(2+)
CC (PubMed:11182241). {ECO:0000250|UniProtKB:P28652,
CC ECO:0000250|UniProtKB:Q13554, ECO:0000269|PubMed:11182241,
CC ECO:0000269|PubMed:15312654, ECO:0000269|PubMed:22579289,
CC ECO:0000269|PubMed:9724800}.
CC -!- INTERACTION:
CC P08413; Q63053: Arc; NbExp=6; IntAct=EBI-916155, EBI-5275794;
CC P08413; P60709: ACTB; Xeno; NbExp=4; IntAct=EBI-916155, EBI-353944;
CC P08413; P62195: PSMC5; Xeno; NbExp=3; IntAct=EBI-916155, EBI-357745;
CC -!- SUBCELLULAR LOCATION: Sarcoplasmic reticulum membrane {ECO:0000250};
CC Peripheral membrane protein {ECO:0000250}; Cytoplasmic side
CC {ECO:0000250}. Synapse {ECO:0000269|PubMed:22579289}. Cytoplasm,
CC cytoskeleton. Cytoplasm, cytoskeleton, microtubule organizing center,
CC centrosome. Note=Colocalizes with the cortical actin cytoskeleton by
CC binding to F-actin in hippocampal cells.
CC -!- INDUCTION: By cocaine in cardiomyocytes. {ECO:0000269|PubMed:16891908,
CC ECO:0000269|PubMed:17272343}.
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:17272343}.
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; M16112; AAA41866.1; -; mRNA.
DR PIR; A26464; A26464.
DR RefSeq; NP_001035815.1; NM_001042356.1.
DR RefSeq; NP_068507.2; NM_021739.2.
DR PDB; 6HCS; X-ray; 2.00 A; B/D/F/H=291-315.
DR PDBsum; 6HCS; -.
DR AlphaFoldDB; P08413; -.
DR SMR; P08413; -.
DR BioGRID; 246430; 15.
DR CORUM; P08413; -.
DR DIP; DIP-36948N; -.
DR IntAct; P08413; 8.
DR MINT; P08413; -.
DR BindingDB; P08413; -.
DR ChEMBL; CHEMBL2610; -.
DR iPTMnet; P08413; -.
DR PhosphoSitePlus; P08413; -.
DR jPOST; P08413; -.
DR PRIDE; P08413; -.
DR GeneID; 24245; -.
DR KEGG; rno:24245; -.
DR UCSC; RGD:2262; rat.
DR CTD; 816; -.
DR RGD; 2262; Camk2b.
DR InParanoid; P08413; -.
DR PhylomeDB; P08413; -.
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:P08413; -.
DR Proteomes; UP000002494; Unplaced.
DR GO; GO:0070161; C:anchoring junction; IEA:UniProtKB-KW.
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; ISO:RGD.
DR GO; GO:0030425; C:dendrite; IDA:RGD.
DR GO; GO:0098978; C:glutamatergic synapse; IDA:SynGO.
DR GO; GO:0005815; C:microtubule organizing center; IEA:UniProtKB-SubCell.
DR GO; GO:0043005; C:neuron projection; IBA:GO_Central.
DR GO; GO:0043204; C:perikaryon; IDA:RGD.
DR GO; GO:0014069; C:postsynaptic density; IDA:RGD.
DR GO; GO:0033017; C:sarcoplasmic reticulum membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0051233; C:spindle midzone; ISO:RGD.
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:0043274; F:phospholipase binding; IDA:RGD.
DR GO; GO:0042803; F:protein homodimerization activity; ISO:RGD.
DR GO; GO:0019901; F:protein kinase binding; IPI: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:0098973; F:structural constituent of postsynaptic actin cytoskeleton; IDA:SynGO.
DR GO; GO:0060466; P:activation of meiosis involved in egg activation; 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:0048858; P:cell projection morphogenesis; IMP:RGD.
DR GO; GO:1905375; P:cellular response to homocysteine; IEP:RGD.
DR GO; GO:0000082; P:G1/S transition of mitotic cell cycle; ISO:RGD.
DR GO; GO:0110088; P:hippocampal neuron apoptotic process; IEP:RGD.
DR GO; GO:0002030; P:inhibitory G protein-coupled receptor phosphorylation; ISO:RGD.
DR GO; GO:0060291; P:long-term synaptic potentiation; IMP:MGI.
DR GO; GO:0007399; P:nervous system development; IEA:UniProtKB-KW.
DR GO; GO:0050885; P:neuromuscular process controlling balance; ISO:RGD.
DR GO; GO:0018105; P:peptidyl-serine phosphorylation; ISO:RGD.
DR GO; GO:2001235; P:positive regulation of apoptotic signaling pathway; ISO:RGD.
DR GO; GO:0061003; P:positive regulation of dendritic spine morphogenesis; IMP:UniProtKB.
DR GO; GO:0010976; P:positive regulation of neuron projection development; IMP:UniProtKB.
DR GO; GO:0032430; P:positive regulation of phospholipase A2 activity; IDA:RGD.
DR GO; GO:0090129; P:positive regulation of synapse maturation; IMP:UniProtKB.
DR GO; GO:0046777; P:protein autophosphorylation; ISS:UniProtKB.
DR GO; GO:0048169; P:regulation of long-term neuronal synaptic plasticity; ISO:RGD.
DR GO; GO:2001222; P:regulation of neuron migration; ISS:UniProtKB.
DR GO; GO:1903076; P:regulation of protein localization to plasma membrane; IGI:ARUK-UCL.
DR GO; GO:0032222; P:regulation of synaptic transmission, cholinergic; ISO:RGD.
DR GO; GO:0046686; P:response to cadmium ion; ISO:RGD.
DR GO; GO:1990911; P:response to psychosocial stress; IEP: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 3D-structure; ATP-binding; Calmodulin-binding; Cytoplasm; Cytoskeleton;
KW Differentiation; Kinase; Membrane; Neurogenesis; Nucleotide-binding;
KW Phosphoprotein; Reference proteome; Sarcoplasmic reticulum;
KW Serine/threonine-protein kinase; Synapse; Transferase.
FT CHAIN 1..542
FT /note="Calcium/calmodulin-dependent protein kinase type II
FT subunit beta"
FT /id="PRO_0000086098"
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 REGION 349..376
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 350..369
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 17
FT /note="Phosphotyrosine"
FT /evidence="ECO:0000250|UniProtKB:P28652"
FT MOD_RES 287
FT /note="Phosphothreonine; by autocatalysis"
FT /evidence="ECO:0000269|PubMed:17272343"
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 367
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:22673903"
FT MOD_RES 371
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P28652"
FT MOD_RES 394
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:22673903"
FT MOD_RES 397
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:22673903"
FT MOD_RES 400
FT /note="Phosphothreonine"
FT /evidence="ECO:0000250|UniProtKB:P28652"
FT MOD_RES 401
FT /note="Phosphothreonine"
FT /evidence="ECO:0007744|PubMed:22673903"
FT MUTAGEN 43
FT /note="K->R: Catalytically inactive form."
FT /evidence="ECO:0000269|PubMed:12873385"
FT MUTAGEN 287
FT /note="T->D: Constitutively active form."
FT /evidence="ECO:0000269|PubMed:12873385"
FT MUTAGEN 303
FT /note="A->R: Blocks calcium/calmodulin binding."
FT /evidence="ECO:0000269|PubMed:12873385"
FT HELIX 296..310
FT /evidence="ECO:0007829|PDB:6HCS"
SQ SEQUENCE 542 AA; 60402 MW; 8A7962A64AE930D0 CRC64;
MATTVTCTRF TDEYQLYEDI GKGAFSVVRR CVKLCTGHEY AAKIINTKKL SARDHQKLER
EARICRLLKH SNIVRLHDSI SEEGFHYLVF DLVTGGELFE DIVAREYYSE ADASHCIQQI
LEAVLHCHQM GVVHRDLKPE NLLLASKCKG AAVKLADFGL AIEVQGDQQA WFGFAGTPGY
LSPEVLRKEA YGKPVDIWAC GVILYILLVG YPPFWDEDQH KLYQQIKAGA YDFPSPEWDT
VTPEAKNLIN QMLTINPAKR ITAHEALKHP WVCQRSTVAS MMHRQETVEC LKKFNARRKL
KGAILTTMLA TRNFSVGRQT TAPATMSTAA SGTTMGLVEQ AKSLLNKKAD GVKPQTNSTK
NSSAITSPKG SLPPAALEPQ TTVIHNPVDG IKESSDSTNT TIEDEDAKAR KQEIIKTTEQ
LIEAVNNGDF EAYAKICDPG LTSFEPEALG NLVEGMDFHR FYFENLLAKN SKPIHTTILN
PHVHVIGEDA ACIAYIRLTQ YIDGQGRPRT SQSEETRVWH RPDGKWQNVH FHCSGAPVAP
LQ
