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P11275 (KCC2A_RAT) Reviewed, UniProtKB/Swiss-Prot

Last modified July 9, 2014. Version 137. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (2) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Interactions·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Calcium/calmodulin-dependent protein kinase type II subunit alpha

Short name=CaM kinase II subunit alpha
Short name=CaMK-II subunit alpha
EC=2.7.11.17
Gene names
Name:Camk2a
OrganismRattus norvegicus (Rat) [Reference proteome]
Taxonomic identifier10116 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeRattus

Protein attributes

Sequence length478 AA.
Sequence statusComplete.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

CaM-kinase II (CAMK2) is a prominent kinase in the central nervous system that may function in long-term potentiation and neurotransmitter release. Member of the NMDAR signaling complex in excitatory synapses it may regulate NMDAR-dependent potentiation of the AMPAR and synaptic plasticity. Ref.8

Catalytic activity

ATP + a protein = ADP + a phosphoprotein.

Enzyme regulation

Autophosphorylation of Thr-286 allows the kinase to switch from a calmodulin-dependent to a calmodulin-independent state. Ref.6

Subunit structure

CAMK2 is composed of four different chains: alpha, beta, gamma, and delta. The different isoforms assemble into homo- or heteromultimeric holoenzymes composed of 8 to 12 subunits. Interacts with BAALC, MPDZ, SYN1, CAMK2N2 and SYNGAP1. Ref.5 Ref.7 Ref.8 Ref.9

Subcellular location

Cell junctionsynapsepresynaptic cell membrane. Cell junctionsynapse. Note: Postsynaptic lipid rafts. 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
   Cellular componentCell junction
Cell membrane
Membrane
Synapse
   LigandATP-binding
Calmodulin-binding
Nucleotide-binding
   Molecular functionKinase
Serine/threonine-protein kinase
Transferase
   PTMPhosphoprotein
   Technical term3D-structure
Complete proteome
Direct protein sequencing
Reference proteome
Gene Ontology (GO)
   Biological_processionotropic glutamate receptor signaling pathway

Inferred from direct assay PubMed 12223541. Source: UniProtKB

peptidyl-serine phosphorylation

Inferred from direct assay PubMed 12951199. Source: RGD

protein autophosphorylation

Inferred from direct assay PubMed 16095822. Source: RGD

protein phosphorylation

Inferred from direct assay PubMed 12401560. Source: RGD

   Cellular_componentcalcium- and calmodulin-dependent protein kinase complex

Traceable author statement PubMed 11264466. Source: UniProtKB

cell junction

Inferred from electronic annotation. Source: UniProtKB-KW

dendrite

Inferred from direct assay PubMed 12223541. Source: UniProtKB

dendrite cytoplasm

Inferred from direct assay PubMed 1419001. Source: BHF-UCL

presynaptic membrane

Inferred from electronic annotation. Source: UniProtKB-SubCell

   Molecular_functionATP binding

Inferred from electronic annotation. Source: UniProtKB-KW

GTPase activating protein binding

Inferred from physical interaction PubMed 12951199. Source: RGD

calmodulin-dependent protein kinase activity

Inferred from direct assay PubMed 12401560PubMed 12951199PubMed 16095822. Source: RGD

protein binding

Inferred from physical interaction PubMed 16120608PubMed 20178748PubMed 20461055. Source: IntAct

Complete GO annotation...

Binary interactions

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 478478Calcium/calmodulin-dependent protein kinase type II subunit alpha
PRO_0000086094

Regions

Domain13 – 271259Protein kinase
Nucleotide binding19 – 279ATP By similarity
Region290 – 30011Calmodulin-binding
Region310 – 32011Interaction with BAALC

Sites

Active site1351Proton acceptor
Binding site421ATP By similarity

Amino acid modifications

Modified residue131Phosphotyrosine By similarity
Modified residue2861Phosphothreonine; by autocatalysis Ref.6

Experimental info

Mutagenesis432 – 4354IRIT → MGTA: Loss of interaction with MPDZ. Ref.8
Sequence conflict3011G → A in AAA41855. Ref.3

Secondary structure

... 478
Helix Strand Turn

Details...

Sequences

Sequence LengthMass (Da)Tools
P11275 [UniParc].

Last modified July 1, 1989. Version 1.
Checksum: 306F416CCE9B5F62

FASTA47854,115
        10         20         30         40         50         60 
MATITCTRFT EEYQLFEELG KGAFSVVRRC VKVLAGQEYA AKIINTKKLS ARDHQKLERE 

        70         80         90        100        110        120 
ARICRLLKHP NIVRLHDSIS EEGHHYLIFD LVTGGELFED IVAREYYSEA DASHCIQQIL 

       130        140        150        160        170        180 
EAVLHCHQMG VVHRDLKPEN LLLASKLKGA AVKLADFGLA IEVEGEQQAW FGFAGTPGYL 

       190        200        210        220        230        240 
SPEVLRKDPY GKPVDLWACG VILYILLVGY PPFWDEDQHR LYQQIKAGAY DFPSPEWDTV 

       250        260        270        280        290        300 
TPEAKDLINK MLTINPSKRI TAAEALKHPW ISHRSTVASC MHRQETVDCL KKFNARRKLK 

       310        320        330        340        350        360 
GAILTTMLAT RNFSGGKSGG NKKNDGVKES SESTNTTIED EDTKVRKQEI IKVTEQLIEA 

       370        380        390        400        410        420 
ISNGDFESYT KMCDPGMTAF EPEALGNLVE GLDFHRFYFE NLWSRNSKPV HTTILNPHIH 

       430        440        450        460        470 
LMGDESACIA YIRITQYLDA GGIPRTAQSE ETRVWHRRDG KWQIVHFHRS GAPSVLPH 

« Hide

References

[1]"Molecular cloning of a brain-specific calcium/calmodulin-dependent protein kinase."
Lin C.R., Kapiloff M.S., Durgerian S., Tatemoto K., Russo A.F., Hanson P., Schulman H., Rosenfeld M.G.
Proc. Natl. Acad. Sci. U.S.A. 84:5962-5966(1987) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA].
[2]"Conserved and variable regions in the subunits of brain type II Ca2+/calmodulin-dependent protein kinase."
Bulleit R.F., Bennett M.K., Molloy S.S., Hurley J.B., Kennedy M.B.
Neuron 1:63-72(1988) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA].
[3]"Functional analysis of a complementary DNA for the 50-kilodalton subunit of calmodulin kinase II."
Hanley R.M., Means A.R., Ono T., Kemp B.E., Burgin K.E., Waxham N., Kelly P.T.
Science 237:293-297(1987) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 132-327.
[4]"Sequence analysis and DNA-protein interactions within the 5' flanking region of the Ca2+/calmodulin-dependent protein kinase II alpha-subunit gene."
Sunyer T., Sahyoun N.
Proc. Natl. Acad. Sci. U.S.A. 87:278-282(1990) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1-6.
[5]"Synaptic vesicle-associated Ca2+/calmodulin-dependent protein kinase II is a binding protein for synapsin I."
Benfenati F., Valtorta F., Rubenstein J.L., Gorelick F.S., Greengard P., Czernik A.J.
Nature 359:417-420(1992) [PubMed] [Europe PMC] [Abstract]
Cited for: PROTEIN SEQUENCE OF 231-236; 238-246 AND 461-476, INTERACTION WITH SYN1.
[6]"Ca2+/calmodulin-dependent protein kinase II: identification of threonine-286 as the autophosphorylation site in the alpha subunit associated with the generation of Ca2+-independent activity."
Thiel G., Czernik A.J., Gorelick F., Nairn A.C., Greengard P.
Proc. Natl. Acad. Sci. U.S.A. 85:6337-6341(1988) [PubMed] [Europe PMC] [Abstract]
Cited for: PROTEIN SEQUENCE OF 282-299, ENZYME REGULATION, PHOSPHORYLATION AT THR-286.
[7]"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.
[8]"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, MUTAGENESIS OF 432-ILE--THR-435, FUNCTION.
[9]"BAALC 1-6-8 protein is targeted to postsynaptic lipid rafts by its N-terminal miristoylation and palmitoylation, and interacts with a, but not b, subunit of Ca2+/calmodulin-dependent protein kinase II."
Wang X., Tian Q.-B., Okano A., Sakagami H., Moon I.S., Kondo H., Endo S., Suzuki T.
J. Neurochem. 92:647-659(2005) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH BAALC, SUBCELLULAR LOCATION.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
J02942 mRNA. Translation: AAA41870.1.
M16960 mRNA. Translation: AAA41855.1.
M29699 Genomic DNA. Translation: AAA40841.1.
PIRA30355.
RefSeqNP_037052.1. NM_012920.1.
UniGeneRn.107499.

3D structure databases

PDBe
RCSB-PDB
PDBj
EntryMethodResolution (Å)ChainPositionsPDBsum
1CDMX-ray2.00B290-314[»]
1CM1X-ray2.00B290-314[»]
1CM4X-ray2.00B290-314[»]
ProteinModelPortalP11275.
SMRP11275. Positions 7-474.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid247435. 13 interactions.
DIPDIP-29639N.
IntActP11275. 14 interactions.
MINTMINT-153011.
STRING10116.ENSRNOP00000025283.

Chemistry

BindingDBP11275.
ChEMBLCHEMBL2359.

PTM databases

PhosphoSiteP11275.

Proteomic databases

PaxDbP11275.
PRIDEP11275.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

GeneID25400.
KEGGrno:25400.
UCSCRGD:2261. rat.

Organism-specific databases

CTD815.
RGD2261. Camk2a.

Phylogenomic databases

eggNOGCOG0515.
HOVERGENHBG108055.
KOK04515.
PhylomeDBP11275.

Enzyme and pathway databases

BRENDA2.7.11.17. 5301.

Gene expression databases

GenevestigatorP11275.

Family and domain databases

InterProIPR020636. Ca/CaM-dep_Ca-dep_prot_Kinase.
IPR013543. Ca/CaM-dep_prot_kinase-assoc.
IPR011009. Kinase-like_dom.
IPR000719. Prot_kinase_dom.
IPR017441. Protein_kinase_ATP_BS.
IPR002290. Ser/Thr_dual-sp_kinase_dom.
IPR008271. Ser/Thr_kinase_AS.
[Graphical view]
PANTHERPTHR24347. PTHR24347. 1 hit.
PfamPF08332. CaMKII_AD. 1 hit.
PF00069. Pkinase. 1 hit.
[Graphical view]
SMARTSM00220. S_TKc. 1 hit.
[Graphical view]
SUPFAMSSF56112. SSF56112. 1 hit.
PROSITEPS00107. PROTEIN_KINASE_ATP. 1 hit.
PS50011. PROTEIN_KINASE_DOM. 1 hit.
PS00108. PROTEIN_KINASE_ST. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

EvolutionaryTraceP11275.
NextBio606489.
PMAP-CutDBP11275.

Entry information

Entry nameKCC2A_RAT
AccessionPrimary (citable) accession number: P11275
Entry history
Integrated into UniProtKB/Swiss-Prot: July 1, 1989
Last sequence update: July 1, 1989
Last modified: July 9, 2014
This is version 137 of the entry and version 1 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Relevant documents

SIMILARITY comments

Index of protein domains and families

PDB cross-references

Index of Protein Data Bank (PDB) cross-references