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Protein

Calcium/calmodulin-dependent protein kinase type II subunit alpha

Gene

Camk2a

Organism
Mus musculus (Mouse)
Status
Reviewed-Annotation score: -Experimental evidence at protein leveli

Functioni

Calcium/calmodulin-dependent protein kinase that functions autonomously after Ca2+/calmodulin-binding and autophosphorylation, and is involved in synaptic plasticity, neurotransmitter release and long-term potentiation. Member of the NMDAR signaling complex in excitatory synapses, it regulates NMDAR-dependent potentiation of the AMPAR and therefore excitatory synaptic transmission (By similarity). Regulates dendritic spine development. Also regulates the migration of developing neurons (By similarity). Phosphorylates the transcription factor FOXO3 to activate its transcriptional activity (PubMed:23805378).By similarity1 Publication

Catalytic activityi

ATP + a protein = ADP + a phosphoprotein.By similarity

Cofactori

Mg2+By similarity

Activity regulationi

Activated by Ca2+/calmodulin. Binding of calmodulin results in conformational change that relieves intrasteric autoinhibition and allows autophosphorylation of Thr-286 which turns the kinase in a constitutively active form and confers to the kinase a Ca2+-independent activity.By similarity

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Binding sitei42ATPPROSITE-ProRule annotation1
Active sitei135Proton acceptor1

Regions

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Nucleotide bindingi19 – 27ATPPROSITE-ProRule annotation9

GO - Molecular functioni

GO - Biological processi

Keywordsi

Molecular functionCalmodulin-binding, Kinase, Serine/threonine-protein kinase, Transferase
LigandATP-binding, Magnesium, Metal-binding, Nucleotide-binding

Enzyme and pathway databases

BRENDAi2.7.11.17 3474
ReactomeiR-MMU-3371571 HSF1-dependent transactivation
R-MMU-399719 Trafficking of AMPA receptors
R-MMU-4086398 Ca2+ pathway
R-MMU-438066 Unblocking of NMDA receptor, glutamate binding and activation
R-MMU-442729 CREB phosphorylation through the activation of CaMKII
R-MMU-442742 CREB phosphorylation through the activation of Ras
R-MMU-442982 Ras activation upon Ca2+ influx through NMDA receptor
R-MMU-5576892 Phase 0 - rapid depolarisation
R-MMU-5578775 Ion homeostasis
R-MMU-5673001 RAF/MAP kinase cascade
R-MMU-877300 Interferon gamma signaling
R-MMU-936837 Ion transport by P-type ATPases

Names & Taxonomyi

Protein namesi
Recommended name:
Calcium/calmodulin-dependent protein kinase type II subunit alpha (EC:2.7.11.17By similarity)
Short name:
CaM kinase II subunit alpha
Short name:
CaMK-II subunit alpha
Gene namesi
Name:Camk2a
OrganismiMus musculus (Mouse)
Taxonomic identifieri10090 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaMyomorphaMuroideaMuridaeMurinaeMusMus
Proteomesi
  • UP000000589 Componenti: Chromosome 18

Organism-specific databases

MGIiMGI:88256 Camk2a

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

Keywords - Cellular componenti

Cell junction, Cell membrane, Cell projection, Cytoplasm, Membrane, Postsynaptic cell membrane, Synapse

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi183E → V: Decreased protein abundance. Decreased autophosphorylation. Changed subcellular localization. Homozygous mice for that mutation are hyperactive and display repetitive behaviors. They also display social deficits and decreased exploratory behavior. 1 Publication1
Mutagenesisi286T → A: Abolishes autophosphorylation. Loss of FOXO3 activation. 1 Publication1
Mutagenesisi286T → A: Phosphomimetic mutant. Enhanced FOXO3 activation. 1 Publication1

Chemistry databases

GuidetoPHARMACOLOGYi1555

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00000860921 – 478Calcium/calmodulin-dependent protein kinase type II subunit alphaAdd BLAST478

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei13PhosphotyrosineCombined sources1
Modified residuei257PhosphoserineBy similarity1
Modified residuei286Phosphothreonine; by autocatalysis1 Publication1
Modified residuei330PhosphoserineCombined sources1
Modified residuei331PhosphoserineCombined sources1
Modified residuei333PhosphoserineCombined sources1
Modified residuei336PhosphothreonineCombined sources1
Modified residuei337PhosphothreonineCombined sources1
Modified residuei404PhosphoserineCombined sources1

Post-translational modificationi

Autophosphorylation of Thr-286 following activation by Ca2+/calmodulin. Phosphorylation of Thr-286 locks the kinase into an activated state.1 Publication

Keywords - PTMi

Phosphoprotein

Proteomic databases

MaxQBiP11798
PaxDbiP11798
PeptideAtlasiP11798
PRIDEiP11798

PTM databases

iPTMnetiP11798
PhosphoSitePlusiP11798
SwissPalmiP11798

Expressioni

Tissue specificityi

Isoform Alpha CaMKII is expressed in brain while isoform Alpha KAP is expressed in skeletal muscle.1 Publication

Gene expression databases

BgeeiENSMUSG00000024617 Expressed in 187 organ(s), highest expression level in brain
ExpressionAtlasiP11798 baseline and differential
GenevisibleiP11798 MM

Interactioni

Subunit structurei

There are 4 genes encoding calcium/calmodulin-dependent protein kinase type II chains: CAMK2A, CAMK2B, CAMK2G and CAMK2D. The corresponding proteins assemble into homo- or heteromultimeric holoenzymes composed of 12 subunits with two hexameric rings stacked one on top of the other (By similarity). Interacts with BAALC. Interacts with MPDZ. Interacts with SYN1. Interacts with CAMK2N2. Interacts with SYNGAP1. Interacts with SYNPO2 (By similarity). Interacts with SHANK3. Interacts with GRIN2B. Interacts with CACNB2. Interacts with LRRC7. Interacts with GRM5 (By similarity).By similarity

Binary interactionsi

GO - Molecular functioni

Protein-protein interaction databases

BioGridi198461, 27 interactors
DIPiDIP-31593N
IntActiP11798, 49 interactors
MINTiP11798
STRINGi10090.ENSMUSP00000099952

Structurei

Secondary structure

1478
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details

3D structure databases

ProteinModelPortaliP11798
SMRiP11798
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiP11798

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini13 – 271Protein kinasePROSITE-ProRule annotationAdd BLAST259

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni290 – 300Calmodulin-bindingAdd BLAST11
Regioni310 – 320Interaction with BAALCBy similarityAdd BLAST11

Sequence similaritiesi

Phylogenomic databases

eggNOGiKOG0033 Eukaryota
ENOG410XNRX LUCA
GeneTreeiENSGT00760000118944
HOGENOMiHOG000233016
HOVERGENiHBG108055
InParanoidiP11798
KOiK04515
TreeFamiTF315229

Family and domain databases

InterProiView protein in InterPro
IPR013543 Ca/CaM-dep_prot_kinase-assoc
IPR039071 CAMK2
IPR011009 Kinase-like_dom_sf
IPR032710 NTF2-like_dom_sf
IPR000719 Prot_kinase_dom
IPR017441 Protein_kinase_ATP_BS
IPR008271 Ser/Thr_kinase_AS
PANTHERiPTHR43940 PTHR43940, 1 hit
PfamiView protein in Pfam
PF08332 CaMKII_AD, 1 hit
PF00069 Pkinase, 1 hit
SMARTiView protein in SMART
SM00220 S_TKc, 1 hit
SUPFAMiSSF54427 SSF54427, 1 hit
SSF56112 SSF56112, 1 hit
PROSITEiView protein in PROSITE
PS00107 PROTEIN_KINASE_ATP, 1 hit
PS50011 PROTEIN_KINASE_DOM, 1 hit
PS00108 PROTEIN_KINASE_ST, 1 hit

Sequences (2+)i

Sequence statusi: Complete.

This entry describes 2 isoformsi produced by alternative splicing. AlignAdd to basket

This entry has 2 described isoforms and 4 potential isoforms that are computationally mapped.iShow all

Isoform Alpha CaMKII (identifier: P11798-1) [UniParc]FASTAAdd to basket

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

« Hide
        10         20         30         40         50
MATITCTRFT EEYQLFEELG KGAFSVVRRC VKVLAGQEYA AKIINTKKLS
60 70 80 90 100
ARDHQKLERE ARICRLLKHP NIVRLHDSIS EEGHHYLIFD LVTGGELFED
110 120 130 140 150
IVAREYYSEA DASHCIQQIL EAVLHCHQMG VVHRDLKPEN LLLASKLKGA
160 170 180 190 200
AVKLADFGLA IEVEGEQQAW FGFAGTPGYL SPEVLRKDPY GKPVDLWACG
210 220 230 240 250
VILYILLVGY PPFWDEDQHR LYQQIKAGAY DFPSPEWDTV TPEAKDLINK
260 270 280 290 300
MLTINPSKRI TAAEALKHPW ISHRSTVASC MHRQETVDCL KKFNARRKLK
310 320 330 340 350
GAILTTMLAT RNFSGGKSGG NKKNDGVKES SESTNTTIED EDTKVRKQEI
360 370 380 390 400
IKVTEQLIEA ISNGDFESYT KMCDPGMTAF EPEALGNLVE GLDFHRFYFE
410 420 430 440 450
NLWSRNSKPV HTTILNPHIH LMGDESACIA YIRITQYLDA GGIPRTAQSE
460 470
ETRVWHRRDG KWQIVHFHRS GAPSVLPH
Length:478
Mass (Da):54,115
Last modified:January 23, 2007 - v2
Checksum:i306F416CCE9B5F62
GO
Isoform Alpha KAP1 Publication (identifier: P11798-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     1-289: Missing.
     290-314: LKKFNARRKLKGAILTTMLATRNFS → MLLFLTLWALVPCLVLLTLYFLSST
     328-328: K → KKRKSSSSVQLM

Note: Has no kinase activity.1 Publication
Show »
Length:200
Mass (Da):22,584
Checksum:i3FB8D6A5C891CBD4
GO

Computationally mapped potential isoform sequencesi

There are 4 potential isoforms mapped to this entry.BLASTAlignShow allAdd to basket
EntryEntry nameProtein names
Gene namesLengthAnnotation
F8WIS9F8WIS9_MOUSE
Calcium/calmodulin-dependent protei...
Camk2a
489Annotation score:
F8WHB5F8WHB5_MOUSE
Calcium/calmodulin-dependent protei...
Camk2a
189Annotation score:
F6WHR9F6WHR9_MOUSE
Calcium/calmodulin-dependent protei...
Camk2a
177Annotation score:
D3Z7K9D3Z7K9_MOUSE
Calcium/calmodulin-dependent protei...
Camk2a mCG_127781
108Annotation score:

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti40A → P in CAA32946 (PubMed:2543961).Curated1
Sequence conflicti169A → R in CAA32946 (PubMed:2543961).Curated1
Sequence conflicti228G → R in CAA32946 (PubMed:2543961).Curated1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_0047671 – 289Missing in isoform Alpha KAP. 1 PublicationAdd BLAST289
Alternative sequenceiVSP_004768290 – 314LKKFN…TRNFS → MLLFLTLWALVPCLVLLTLY FLSST in isoform Alpha KAP. 1 PublicationAdd BLAST25
Alternative sequenceiVSP_004769328K → KKRKSSSSVQLM in isoform Alpha KAP. 1 Publication1

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
X14836 mRNA Translation: CAA32946.1
X87142 mRNA Translation: CAA60620.1
AK083245 mRNA Translation: BAC38829.1
BC031745 mRNA Translation: AAH31745.1
CCDSiCCDS29276.1 [P11798-1]
CCDS29277.1 [P11798-2]
PIRiJC6083
S04365
RefSeqiNP_001273738.1, NM_001286809.1
NP_033922.1, NM_009792.3 [P11798-2]
NP_803126.1, NM_177407.4 [P11798-1]
UniGeneiMm.131530
Mm.446530

Genome annotation databases

EnsembliENSMUST00000102888; ENSMUSP00000099952; ENSMUSG00000024617 [P11798-1]
ENSMUST00000115295; ENSMUSP00000110950; ENSMUSG00000024617 [P11798-2]
GeneIDi12322
KEGGimmu:12322
UCSCiuc008fbg.2 mouse [P11798-1]
uc008fbh.2 mouse [P11798-2]

Keywords - Coding sequence diversityi

Alternative splicing

Similar proteinsi

Entry informationi

Entry nameiKCC2A_MOUSE
AccessioniPrimary (citable) accession number: P11798
Secondary accession number(s): Q61284, Q6ZWN4
Entry historyiIntegrated into UniProtKB/Swiss-Prot: October 1, 1989
Last sequence update: January 23, 2007
Last modified: September 12, 2018
This is version 194 of the entry and version 2 of the sequence. See complete history.
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

3D-structure, Complete proteome, Direct protein sequencing, Reference proteome
UniProt is an ELIXIR core data resource
Main funding by: National Institutes of Health

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