Calcium/calmodulin-dependent protein kinase type II subunit beta

Preferred order of sections

Names and origin

Protein names

Recommended name:
Calcium/calmodulin-dependent protein kinase type II subunit beta
Short name=CaM kinase II subunit beta
Short name=CaMK-II subunit beta
EC=2.7.11.17

Gene names

Name:	Camk2b
Synonyms:	Camk2d

Organism

Mus musculus (Mouse) [Reference proteome]

Taxonomic identifier

10090 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Glires › Rodentia › Sciurognathi › Muroidea › Muridae › Murinae › Mus › Mus

Protein attributes

Sequence length	542 AA.
Sequence status	Complete.
Protein existence	Evidence at protein level

General annotation (Comments)

Function	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. Ref.9
Catalytic activity	ATP + a protein = ADP + a phosphoprotein.
Enzyme regulation	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.
Subunit structure	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 By similarity.
Subcellular location	Cytoplasm › cytoskeleton. Cytoplasm › cytoskeleton › centrosome. Sarcoplasmic reticulum membrane; Peripheral membrane protein; Cytoplasmic side By similarity.
Domain	The CAMK2 protein kinases contain a unique C-terminal subunit association domain responsible for oligomerization.
Post-translational modification	Autophosphorylation of Thr-287 following activation by Ca²⁺/calmodulin. Phosphorylation of Thr-287 locks the kinase into an activated state.
Disruption phenotype	Impaired long-term potentiation (LTP) and hippocampus-dependent learning. Ref.9
Sequence similarities	Belongs to the protein kinase superfamily. CAMK Ser/Thr protein kinase family. CaMK subfamily. Contains 1 protein kinase domain.

Ontologies

Keywords
Biological process	Differentiation Neurogenesis
Cellular component	Cytoplasm Cytoskeleton Membrane Sarcoplasmic reticulum
Ligand	ATP-binding Calmodulin-binding Nucleotide-binding
Molecular function	Kinase Serine/threonine-protein kinase Transferase
PTM	Phosphoprotein
Technical term	Complete proteome Direct protein sequencing Reference proteome
Gene Ontology (GO)
Biological_process	G1/S transition of mitotic cell cycle Inferred from mutant phenotype PubMed 12660151. Source: MGI activation of meiosis involved in egg activation Inferred from mutant phenotype PubMed 9882483. Source: MGI calcium ion transport Inferred from mutant phenotype PubMed 12660151. Source: MGI inhibitory G-protein coupled receptor phosphorylation Inferred from direct assay PubMed 19332541. Source: MGI neuromuscular process controlling balance Inferred from mutant phenotype PubMed 19503086. Source: MGI peptidyl-serine phosphorylation Inferred from direct assay PubMed 19332541. Source: MGI positive regulation of apoptotic signaling pathway Inferred from direct assay PubMed 17367784. Source: MGI positive regulation of dendritic spine morphogenesis Inferred from sequence or structural similarity. Source: UniProtKB positive regulation of neuron projection development Inferred from sequence or structural similarity. Source: UniProtKB positive regulation of synapse maturation Inferred from sequence or structural similarity. Source: UniProtKB protein autophosphorylation Inferred from mutant phenotype PubMed 12660151. Source: MGI regulation of long-term neuronal synaptic plasticity Inferred from mutant phenotype PubMed 19503086. Source: MGI regulation of synaptic transmission, cholinergic Inferred from mutant phenotype PubMed 19332541. Source: MGI response to cadmium ion Inferred from direct assay PubMed 17367784. Source: MGI
Cellular_component	calcium- and calmodulin-dependent protein kinase complex Traceable author statement PubMed 11264466. Source: UniProtKB cytosol Inferred from direct assay PubMed 9882483. Source: MGI microtubule organizing center Inferred from electronic annotation. Source: UniProtKB-SubCell sarcoplasmic reticulum membrane Inferred from electronic annotation. Source: UniProtKB-SubCell spindle midzone Inferred from direct assay PubMed 9882483. Source: MGI
Molecular_function	ATP binding Inferred from electronic annotation. Source: UniProtKB-KW calmodulin-dependent protein kinase activity Inferred from direct assay PubMed 9882483. Source: MGI
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
Arc	Q9WV31	2	EBI-397029,EBI-397779

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Chain

1 – 542

542

Calcium/calmodulin-dependent protein kinase type II subunit beta

PRO_0000086097

Regions

Domain

14 – 272

259

Protein kinase

Nucleotide binding

20 – 28

9

ATP By similarity

Region

283 – 292

10

Autoinhibitory domain By similarity

Region

291 – 301

11

Calmodulin-binding

Sites

Active site

136

1

Proton acceptor By similarity

Binding site

43

1

ATP By similarity

Amino acid modifications

Modified residue

17

1

Phosphotyrosine Ref.7

Modified residue

287

1

Phosphothreonine; by autocatalysis Ref.6 Ref.8

Modified residue

306

1

Phosphothreonine; by autocatalysis By similarity

Modified residue

307

1

Phosphothreonine; by autocatalysis By similarity

Modified residue

315

1

Phosphoserine Ref.5

Modified residue

367

1

Phosphoserine Ref.8

Modified residue

397

1

Phosphoserine Ref.8

Experimental info

Mutagenesis

303

1

A → R: Blocks calcium/calmodulin binding. Ref.9

Sequence conflict

19

1

D → E in CAA45160. Ref.1

Sequences

Sequence

Length

Mass (Da)

Tools

P28652 [UniParc].

Last modified May 2, 2006. Version 2.
Checksum: 8A7962A6495FD0D0
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FASTA

542

60,461

        10         20         30         40         50         60 
MATTVTCTRF TDEYQLYEDI GKGAFSVVRR CVKLCTGHEY AAKIINTKKL SARDHQKLER 

        70         80         90        100        110        120 
EARICRLLKH SNIVRLHDSI SEEGFHYLVF DLVTGGELFE DIVAREYYSE ADASHCIQQI 

       130        140        150        160        170        180 
LEAVLHCHQM GVVHRDLKPE NLLLASKCKG AAVKLADFGL AIEVQGDQQA WFGFAGTPGY 

       190        200        210        220        230        240 
LSPEVLRKEA YGKPVDIWAC GVILYILLVG YPPFWDEDQH KLYQQIKAGA YDFPSPEWDT 

       250        260        270        280        290        300 
VTPEAKNLIN QMLTINPAKR ITAHEALKHP WVCQRSTVAS MMHRQETVEC LKKFNARRKL 

       310        320        330        340        350        360 
KGAILTTMLA TRNFSVGRQT TAPATMSTAA SGTTMGLVEQ AKSLLNKKAD GVKPQTNSTK 

       370        380        390        400        410        420 
NSSAITSPKG SLPPAALEPQ TTVIHNPVDG IKESSDSTNT TIEDEDAKAR KQEIIKTTEQ 

       430        440        450        460        470        480 
LIEAVNNGDF EAYAKICDPG LTSFEPEALG NLVEGMDFHR FYFENLLAKN SKPIHTTILN 

       490        500        510        520        530        540 
PHVHVIGEDA ACIAYIRLTQ YIDGQGRPRT SQSEETRVWH RRDGKWQNVH FHCSGAPVAP 


LQ

« Hide

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Structure, expression, and chromosome location of the gene for the beta subunit of brain-specific Ca2+/calmodulin-dependent protein kinase II identified by transgene integration in an embryonic lethal mouse mutant." Karls U., Mueller U., Gilbert D.J., Copeland N.G., Jenkins N.A., Harbers K. Mol. Cell. Biol. 12:3644-3652(1992) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA]. Strain: BALB/c. Tissue: Brain.
[2]	"The transcriptional landscape of the mammalian genome." Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N., Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K., Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J. Hayashizaki Y. Science 309:1559-1563(2005) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. Strain: C57BL/6J. Tissue: Cerebellum.
[3]	"Lineage-specific biology revealed by a finished genome assembly of the mouse." Church D.M., Goodstadt L., Hillier L.W., Zody M.C., Goldstein S., She X., Bult C.J., Agarwala R., Cherry J.L., DiCuccio M., Hlavina W., Kapustin Y., Meric P., Maglott D., Birtle Z., Marques A.C., Graves T., Zhou S. Ponting C.P. PLoS Biol. 7:E1000112-E1000112(2009) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. Strain: C57BL/6J.
[4]	Lubec G., Sunyer B., Chen W.-Q. Submitted (JAN-2009) to UniProtKB Cited for: PROTEIN SEQUENCE OF 136-147, MASS SPECTROMETRY. Strain: OF1. Tissue: Hippocampus.
[5]	"Proteomic analysis of in vivo phosphorylated synaptic proteins." Collins M.O., Yu L., Coba M.P., Husi H., Campuzano I., Blackstock W.P., Choudhary J.S., Grant S.G. J. Biol. Chem. 280:5972-5982(2005) [PubMed] [Europe PMC] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-315, MASS SPECTROMETRY. Tissue: Forebrain.
[6]	"Comprehensive identification of phosphorylation sites in postsynaptic density preparations." Trinidad J.C., Specht C.G., Thalhammer A., Schoepfer R., Burlingame A.L. Mol. Cell. Proteomics 5:914-922(2006) [PubMed] [Europe PMC] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-287, MASS SPECTROMETRY. Tissue: Brain.
[7]	"Large-scale identification and evolution indexing of tyrosine phosphorylation sites from murine brain." Ballif B.A., Carey G.R., Sunyaev S.R., Gygi S.P. J. Proteome Res. 7:311-318(2008) [PubMed] [Europe PMC] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT TYR-17, MASS SPECTROMETRY. Tissue: Brain.
[8]	"Qualitative and quantitative analyses of protein phosphorylation in naive and stimulated mouse synaptosomal preparations." Munton R.P., Tweedie-Cullen R., Livingstone-Zatchej M., Weinandy F., Waidelich M., Longo D., Gehrig P., Potthast F., Rutishauser D., Gerrits B., Panse C., Schlapbach R., Mansuy I.M. Mol. Cell. Proteomics 6:283-293(2007) [PubMed] [Europe PMC] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-367; THR-287 AND SER-397, MASS SPECTROMETRY. Tissue: Brain cortex.
[9]	"{beta}CaMKII plays a nonenzymatic role in hippocampal synaptic plasticity and learning by targeting {alpha}CaMKII to synapses." Borgesius N.Z., van Woerden G.M., Buitendijk G.H., Keijzer N., Jaarsma D., Hoogenraad C.C., Elgersma Y. J. Neurosci. 31:10141-10148(2011) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION, DISRUPTION PHENOTYPE, MUTAGENESIS OF ALA-303.
+	Additional computationally mapped references.

Cross-references

Sequence databases
EMBL GenBank DDBJ	X63615 mRNA. Translation: CAA45160.1. AK163698 mRNA. Translation: BAE37464.1. AL611926, AL645469 Genomic DNA. Translation: CAI24948.1. AL645469, AL611926 Genomic DNA. Translation: CAI25258.1.
IPI	IPI00474502.
PIR	A45025.
RefSeq	NP_031621.3. NM_007595.5.
UniGene	Mm.439733.
3D structure databases
ProteinModelPortal	P28652.
SMR	P28652. Positions 10-536.
ModBase	Search...
Protein-protein interaction databases
DIP	DIP-31582N.
IntAct	P28652. 10 interactions.
MINT	MINT-136473.
PTM databases
PhosphoSite	P28652.
Proteomic databases
PaxDb	P28652.
PRIDE	P28652.
Protocols and materials databases
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENSMUST00000109813; ENSMUSP00000105438; ENSMUSG00000057897. ENSMUST00000109815; ENSMUSP00000105440; ENSMUSG00000057897.
GeneID	12323.
KEGG	mmu:12323.
Organism-specific databases
CTD	816.
MGI	MGI:88257. Camk2b.
Phylogenomic databases
eggNOG	COG0515.
GeneTree	ENSGT00680000099653.
HOGENOM	HOG000233016.
HOVERGEN	HBG108055.
KO	K04515.
Enzyme and pathway databases
BRENDA	2.7.11.17. 3474.
Gene expression databases
ArrayExpress	P28652.
Bgee	P28652.
Genevestigator	P28652.
GermOnline	ENSMUSG00000057897. Mus musculus.
Family and domain databases
InterPro	IPR020636. Ca/CaM-dep_Ca-dep_prot_Kinase. IPR013543. Ca/CaM-dep_prot_kinase-assoc. IPR011009. Kinase-like_dom. IPR000719. Prot_kinase_cat_dom. IPR017441. Protein_kinase_ATP_BS. IPR002290. Ser/Thr_dual-sp_kinase_dom. IPR008271. Ser/Thr_kinase_AS. [Graphical view]
PANTHER	PTHR24347. PTHR24347. 1 hit.
Pfam	PF08332. CaMKII_AD. 1 hit. PF00069. Pkinase. 1 hit. [Graphical view]
SMART	SM00220. S_TKc. 1 hit. [Graphical view]
SUPFAM	SSF56112. Kinase_like. 1 hit.
PROSITE	PS00107. PROTEIN_KINASE_ATP. 1 hit. PS50011. PROTEIN_KINASE_DOM. 1 hit. PS00108. PROTEIN_KINASE_ST. 1 hit. [Graphical view]
ProtoNet	Search...
Other
BindingDB	P28652.
ChEMBL	CHEMBL4735.
ChiTaRS	CAMK2B. mouse.
NextBio	280904.
SOURCE	Search...

Entry information

Entry name

KCC2B_MOUSE

Accession

Primary (citable) accession number: P28652
Secondary accession number(s): Q5SVH9

Entry history

Integrated into UniProtKB/Swiss-Prot:	December 1, 1992
Last sequence update:	May 2, 2006
Last modified:	May 1, 2013
This is version 134 of the entry and version 2 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program

Relevant documents

Human and mouse protein kinases

Human and mouse protein kinases: classification and index

MGD cross-references

Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot

SIMILARITY comments

Index of protein domains and families

Preferred order of sections

Names and origin

Protein attributes

General annotation (Comments)

Ontologies

Binary interactions

With

Entry

#Exp.

IntAct

Notes

Sequence annotation (Features)

Molecule processing

Regions

Sites

Amino acid modifications

Experimental info

Sequences

References

Cross-references

Sequence databases

3D structure databases

Protein-protein interaction databases

PTM databases

Proteomic databases

Protocols and materials databases

Genome annotation databases

Organism-specific databases

Phylogenomic databases

Enzyme and pathway databases

Gene expression databases

Family and domain databases

Other

Entry information

Relevant documents