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Protein

Calcium/calmodulin-dependent protein kinase type II subunit beta

Gene

Camk2b

Organism
Rattus norvegicus (Rat)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

Calcium/calmodulin-dependent protein kinase that functions autonomously after Ca2+/calmodulin-binding and autophosphorylation, and is involved in dendritic spine and synapse formation, neuronal plasticity and regulation of sarcoplasmic reticulum Ca2+ transport in skeletal muscle. In neurons, plays an essential structural role in the reorganization of the actin cytoskeleton during plasticity by binding and bundling actin filaments in a kinase-independent manner. This structural function is required for correct targeting of CaMK2A, which acts downstream of NMDAR to promote dendritic spine and synapse formation and maintain synaptic plasticity which enables long-term potentiation (LTP) and hippocampus-dependent learning. In developing hippocampal neurons, promotes arborization of the dendritic tree and in mature neurons, promotes dendritic remodeling. Participates in the modulation of skeletal muscle function in response to exercise. In slow-twitch muscles, is involved in regulation of sarcoplasmic reticulum (SR) Ca2+ transport and in fast-twitch muscle participates in the control of Ca2+ release from the SR through phosphorylation of triadin, a ryanodine receptor-coupling factor, and phospholamban (PLN/PLB), an endogenous inhibitor of SERCA2A/ATP2A2.3 Publications

Catalytic activityi

ATP + a protein = ADP + a phosphoprotein.

Enzyme regulationi

Activated by Ca2+/calmodulin. Binding of calmodulin results in conformational change that relieves intrasteric autoinhibition and allows autophosphorylation of Thr-287 which turns the kinase in a constitutively active form and confers to the kinase a Ca2+-independent activity.

Sites

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Binding sitei43 – 431ATPPROSITE-ProRule annotation
Active sitei136 – 1361Proton acceptorPROSITE-ProRule annotation

Regions

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Nucleotide bindingi20 – 289ATPPROSITE-ProRule annotation

GO - Molecular functioni

  • ATP binding Source: UniProtKB-KW
  • calmodulin-dependent protein kinase activity Source: RGD
  • phospholipase binding Source: RGD
  • protein kinase binding Source: RGD

GO - Biological processi

  • cell projection morphogenesis Source: RGD
  • long-term synaptic potentiation Source: MGI
  • positive regulation of dendritic spine morphogenesis Source: UniProtKB
  • positive regulation of neuron projection development Source: UniProtKB
  • positive regulation of phospholipase A2 activity Source: RGD
  • positive regulation of synapse maturation Source: UniProtKB
  • protein autophosphorylation Source: UniProtKB
Complete GO annotation...

Keywords - Molecular functioni

Kinase, Serine/threonine-protein kinase, Transferase

Keywords - Biological processi

Differentiation, Neurogenesis

Keywords - Ligandi

ATP-binding, Calmodulin-binding, Nucleotide-binding

Enzyme and pathway databases

BRENDAi2.7.11.17. 5301.

Names & Taxonomyi

Protein namesi
Recommended name:
Calcium/calmodulin-dependent protein kinase type II subunit beta (EC:2.7.11.17)
Short name:
CaM kinase II subunit beta
Short name:
CaMK-II subunit beta
Gene namesi
Name:Camk2b
OrganismiRattus norvegicus (Rat)
Taxonomic identifieri10116 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeRattus
Proteomesi
  • UP000002494 Componenti: Unplaced

Organism-specific databases

RGDi2262. Camk2b.

Subcellular locationi

GO - Cellular componenti

  • dendrite Source: RGD
  • microtubule organizing center Source: UniProtKB-SubCell
  • perikaryon Source: RGD
  • postsynaptic density Source: RGD
  • sarcoplasmic reticulum membrane Source: UniProtKB-SubCell
Complete GO annotation...

Keywords - Cellular componenti

Cytoplasm, Cytoskeleton, Membrane, Sarcoplasmic reticulum

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Mutagenesisi43 – 431K → R: Catalytically inactive form. 1 Publication
Mutagenesisi287 – 2871T → D: Constitutively active form. 1 Publication
Mutagenesisi303 – 3031A → R: Blocks calcium/calmodulin binding. 1 Publication

Chemistry

ChEMBLiCHEMBL2111382.

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Chaini1 – 542542Calcium/calmodulin-dependent protein kinase type II subunit betaPRO_0000086098Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Modified residuei17 – 171PhosphotyrosineBy similarity
Modified residuei287 – 2871Phosphothreonine; by autocatalysis1 Publication
Modified residuei306 – 3061Phosphothreonine; by autocatalysisBy similarity
Modified residuei307 – 3071Phosphothreonine; by autocatalysisBy similarity
Modified residuei367 – 3671PhosphoserineCombined sources
Modified residuei371 – 3711PhosphoserineBy similarity
Modified residuei394 – 3941PhosphoserineCombined sources
Modified residuei397 – 3971PhosphoserineCombined sources
Modified residuei400 – 4001PhosphothreonineBy similarity
Modified residuei401 – 4011PhosphothreonineCombined sources

Post-translational modificationi

Autophosphorylation of Thr-287 following activation by Ca2+/calmodulin. Phosphorylation of Thr-287 locks the kinase into an activated state.1 Publication

Keywords - PTMi

Phosphoprotein

Proteomic databases

PRIDEiP08413.

PTM databases

iPTMnetiP08413.
PhosphoSiteiP08413.

Expressioni

Inductioni

By cocaine in cardiomyocytes.2 Publications

Interactioni

Subunit structurei

CAMK2 is composed of 4 different chains: alpha (CAMK2A), beta (CAMK2B), gamma (CAMK2G), and delta (CAMK2D). The different isoforms assemble into homo- or heteromultimeric holoenzymes composed of 12 subunits with two hexameric rings stacked one on top of the other. Interacts with SYNGAP1, CAMK2N2 and MPDZ.2 Publications

Binary interactionsi

WithEntry#Exp.IntActNotes
ArcQ630536EBI-916155,EBI-5275794
PSMC5P621953EBI-916155,EBI-357745From a different organism.

GO - Molecular functioni

  • phospholipase binding Source: RGD
  • protein kinase binding Source: RGD

Protein-protein interaction databases

BioGridi246430. 8 interactions.
DIPiDIP-36948N.
IntActiP08413. 4 interactions.

Structurei

3D structure databases

ProteinModelPortaliP08413.
SMRiP08413. Positions 11-301, 403-536.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Domaini14 – 272259Protein kinasePROSITE-ProRule annotationAdd
BLAST

Region

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Regioni283 – 29210Autoinhibitory domainBy similarity
Regioni291 – 30111Calmodulin-bindingAdd
BLAST

Domaini

The CAMK2 protein kinases contain a unique C-terminal subunit association domain responsible for oligomerization.

Sequence similaritiesi

Contains 1 protein kinase domain.PROSITE-ProRule annotation

Phylogenomic databases

HOGENOMiHOG000233016.
HOVERGENiHBG108055.
InParanoidiP08413.
KOiK04515.
PhylomeDBiP08413.

Family and domain databases

Gene3Di3.10.450.50. 1 hit.
InterProiIPR020636. Ca/CaM-dep_Ca-dep_prot_Kinase.
IPR013543. Ca/CaM-dep_prot_kinase-assoc.
IPR011009. Kinase-like_dom.
IPR032710. NTF2-like_dom.
IPR000719. Prot_kinase_dom.
IPR017441. Protein_kinase_ATP_BS.
IPR008271. Ser/Thr_kinase_AS.
[Graphical view]
PANTHERiPTHR24347. PTHR24347. 2 hits.
PfamiPF08332. CaMKII_AD. 1 hit.
PF00069. Pkinase. 1 hit.
[Graphical view]
SMARTiSM00220. S_TKc. 1 hit.
[Graphical view]
SUPFAMiSSF54427. SSF54427. 1 hit.
SSF56112. SSF56112. 1 hit.
PROSITEiPS00107. PROTEIN_KINASE_ATP. 1 hit.
PS50011. PROTEIN_KINASE_DOM. 1 hit.
PS00108. PROTEIN_KINASE_ST. 1 hit.
[Graphical view]

Sequencei

Sequence statusi: Complete.

P08413-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MATTVTCTRF TDEYQLYEDI GKGAFSVVRR CVKLCTGHEY AAKIINTKKL
60 70 80 90 100
SARDHQKLER EARICRLLKH SNIVRLHDSI SEEGFHYLVF DLVTGGELFE
110 120 130 140 150
DIVAREYYSE ADASHCIQQI LEAVLHCHQM GVVHRDLKPE NLLLASKCKG
160 170 180 190 200
AAVKLADFGL AIEVQGDQQA WFGFAGTPGY LSPEVLRKEA YGKPVDIWAC
210 220 230 240 250
GVILYILLVG YPPFWDEDQH KLYQQIKAGA YDFPSPEWDT VTPEAKNLIN
260 270 280 290 300
QMLTINPAKR ITAHEALKHP WVCQRSTVAS MMHRQETVEC LKKFNARRKL
310 320 330 340 350
KGAILTTMLA TRNFSVGRQT TAPATMSTAA SGTTMGLVEQ AKSLLNKKAD
360 370 380 390 400
GVKPQTNSTK NSSAITSPKG SLPPAALEPQ TTVIHNPVDG IKESSDSTNT
410 420 430 440 450
TIEDEDAKAR KQEIIKTTEQ LIEAVNNGDF EAYAKICDPG LTSFEPEALG
460 470 480 490 500
NLVEGMDFHR FYFENLLAKN SKPIHTTILN PHVHVIGEDA ACIAYIRLTQ
510 520 530 540
YIDGQGRPRT SQSEETRVWH RPDGKWQNVH FHCSGAPVAP LQ
Length:542
Mass (Da):60,402
Last modified:August 1, 1988 - v1
Checksum:i8A7962A64AE930D0
GO

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
M16112 mRNA. Translation: AAA41866.1.
PIRiA26464.
RefSeqiNP_001035815.1. NM_001042356.1.
NP_068507.2. NM_021739.2.
UniGeneiRn.9743.

Genome annotation databases

GeneIDi24245.
KEGGirno:24245.
UCSCiRGD:2262. rat.

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
M16112 mRNA. Translation: AAA41866.1.
PIRiA26464.
RefSeqiNP_001035815.1. NM_001042356.1.
NP_068507.2. NM_021739.2.
UniGeneiRn.9743.

3D structure databases

ProteinModelPortaliP08413.
SMRiP08413. Positions 11-301, 403-536.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi246430. 8 interactions.
DIPiDIP-36948N.
IntActiP08413. 4 interactions.

Chemistry

ChEMBLiCHEMBL2111382.

PTM databases

iPTMnetiP08413.
PhosphoSiteiP08413.

Proteomic databases

PRIDEiP08413.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

GeneIDi24245.
KEGGirno:24245.
UCSCiRGD:2262. rat.

Organism-specific databases

CTDi816.
RGDi2262. Camk2b.

Phylogenomic databases

HOGENOMiHOG000233016.
HOVERGENiHBG108055.
InParanoidiP08413.
KOiK04515.
PhylomeDBiP08413.

Enzyme and pathway databases

BRENDAi2.7.11.17. 5301.

Miscellaneous databases

PROiP08413.

Family and domain databases

Gene3Di3.10.450.50. 1 hit.
InterProiIPR020636. Ca/CaM-dep_Ca-dep_prot_Kinase.
IPR013543. Ca/CaM-dep_prot_kinase-assoc.
IPR011009. Kinase-like_dom.
IPR032710. NTF2-like_dom.
IPR000719. Prot_kinase_dom.
IPR017441. Protein_kinase_ATP_BS.
IPR008271. Ser/Thr_kinase_AS.
[Graphical view]
PANTHERiPTHR24347. PTHR24347. 2 hits.
PfamiPF08332. CaMKII_AD. 1 hit.
PF00069. Pkinase. 1 hit.
[Graphical view]
SMARTiSM00220. S_TKc. 1 hit.
[Graphical view]
SUPFAMiSSF54427. SSF54427. 1 hit.
SSF56112. SSF56112. 1 hit.
PROSITEiPS00107. PROTEIN_KINASE_ATP. 1 hit.
PS50011. PROTEIN_KINASE_DOM. 1 hit.
PS00108. PROTEIN_KINASE_ST. 1 hit.
[Graphical view]
ProtoNetiSearch...

Publicationsi

« Hide 'large scale' publications
  1. "Deduced primary structure of the beta subunit of brain type II Ca2+/calmodulin-dependent protein kinase determined by molecular cloning."
    Bennett M.K., Kennedy M.B.
    Proc. Natl. Acad. Sci. U.S.A. 84:1794-1798(1987) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA].
    Tissue: Brain.
  2. "CaMKIIbeta functions as an F-actin targeting module that localizes CaMKIIalpha/beta heterooligomers to dendritic spines."
    Shen K., Teruel M.N., Subramanian K., Meyer T.
    Neuron 21:593-606(1998) [PubMed] [Europe PMC] [Abstract]
    Cited for: SUBCELLULAR LOCATION, TISSUE SPECIFICITY.
  3. "Characterization of a calmodulin kinase II inhibitor protein in brain."
    Chang B.H., Mukherji S., Soderling T.R.
    Proc. Natl. Acad. Sci. U.S.A. 95:10890-10895(1998) [PubMed] [Europe PMC] [Abstract]
    Cited for: INTERACTION WITH CAMK2N2.
  4. "Selective regulation of neurite extension and synapse formation by the beta but not the alpha isoform of CaMKII."
    Fink C.C., Bayer K.U., Myers J.W., Ferrell J.E. Jr., Schulman H., Meyer T.
    Neuron 39:283-297(2003) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION IN SYNAPSE FORMATION, SUBCELLULAR LOCATION, MUTAGENESIS OF LYS-43; THR-287 AND ALA-303.
  5. "SynGAP-MUPP1-CaMKII synaptic complexes regulate p38 MAP kinase activity and NMDA receptor-dependent synaptic AMPA receptor potentiation."
    Krapivinsky G., Medina I., Krapivinsky L., Gapon S., Clapham D.E.
    Neuron 43:563-574(2004) [PubMed] [Europe PMC] [Abstract]
    Cited for: INTERACTION WITH SYNGAP1 AND MPDZ, FUNCTION.
  6. "Cocaine activates calcium/calmodulin kinase II and causes cardiomyocyte hypertrophy."
    Henning R.J., Cuevas J.
    J. Cardiovasc. Pharmacol. 48:802-813(2006) [PubMed] [Europe PMC] [Abstract]
    Cited for: INDUCTION BY COCAINE.
  7. "Regulation and function of Ca2+-calmodulin-dependent protein kinase II of fast-twitch rat skeletal muscle."
    Rose A.J., Alsted T.J., Kobberoe J.B., Richter E.A.
    J. Physiol. (Lond.) 580:993-1005(2007) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION, INDUCTION, PHOSPHORYLATION AT THR-287.
  8. "Quantitative maps of protein phosphorylation sites across 14 different rat organs and tissues."
    Lundby A., Secher A., Lage K., Nordsborg N.B., Dmytriyev A., Lundby C., Olsen J.V.
    Nat. Commun. 3:876-876(2012) [PubMed] [Europe PMC] [Abstract]
    Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-367; SER-394; SER-397 AND THR-401, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].

Entry informationi

Entry nameiKCC2B_RAT
AccessioniPrimary (citable) accession number: P08413
Entry historyi
Integrated into UniProtKB/Swiss-Prot: August 1, 1988
Last sequence update: August 1, 1988
Last modified: June 8, 2016
This is version 146 of the entry and version 1 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. SIMILARITY comments
    Index of protein domains and families

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.