Calcium/calmodulin-dependent protein kinase type II subunit alpha

Names and origin

Protein attributes

General annotation (Comments)

Ontologies

Binary interactions

Alternative products

Sequence annotation (Features)

Sequences

References

Cross-references

Entry information

Relevant documents

Names and origin

Protein attributes

General annotation (Comments)

Ontologies

Binary interactions

Alternative products

Sequence annotation (Features)

Sequences

References

Cross-references

Entry information

Relevant documents

Molecule processing

Regions

Sites

Amino acid modifications

Natural variations

Experimental info

Secondary structure

Sequence databases

3D structure databases

Protein-protein interaction databases

PTM databases

Proteomic databases

Genome annotation databases

Organism-specific databases

Phylogenomic databases

Enzyme and pathway databases

Gene expression databases

Family and domain databases

Other Resources

With

Entry

#Exp.

IntAct

Notes

Molecule processing

Regions

Sites

Amino acid modifications

Natural variations

Experimental info

Secondary structure

Sequence databases

3D structure databases

Protein-protein interaction databases

PTM databases

Proteomic databases

Genome annotation databases

Organism-specific databases

Phylogenomic databases

Enzyme and pathway databases

Gene expression databases

Family and domain databases

Other Resources

Protein names

Recommended 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

Organism

Mus musculus (Mouse)

Taxonomic identifier

10090 [NCBI]

Taxonomic lineage

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

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Sequence length	478 AA.
Sequence status	Complete.
Protein existence	Evidence at protein level.

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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 By similarity.
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 By similarity.
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 By similarity.
Subcellular location	Isoform Alpha KAP: Cytoplasm Probable. Cell junction › synapse › presynaptic cell membrane By similarity. Cell junction › synapse By similarity. Note: Postsynaptic lipid rafts By similarity.
Tissue specificity	Isoform Alpha CaMKII is expressed in brain while isoform Alpha KAP is expressed in skeletal muscle.
Sequence similarities	Belongs to the protein kinase superfamily. CAMK Ser/Thr protein kinase family. CaMK subfamily. Contains 1 protein kinase domain.

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Keywords
Cellular component	Cell junction Cell membrane Cytoplasm Membrane Synapse
Coding sequence diversity	Alternative splicing
Ligand	ATP-binding Calmodulin-binding Nucleotide-binding
Molecular function	Kinase Serine/threonine-protein kinase Transferase
PTM	Phosphoprotein
Technical term	3D-structure Direct protein sequencing
Gene Ontology (GO)
Biological process	G1/S transition of mitotic cell cycle Inferred from mutant phenotype. Source: MGI calcium ion transport Inferred from mutant phenotype. Source: MGI protein amino acid autophosphorylation Inferred from mutant phenotype. Source: MGI regulation of neuronal synaptic plasticity Inferred from mutant phenotype. Source: MGI regulation of neurotransmitter secretion Inferred from mutant phenotype. Source: MGI
Cellular component	calcium- and calmodulin-dependent protein kinase complex Traceable author statement. Source: UniProtKB cell junction Inferred from electronic annotation. Source: UniProtKB-KW cytoplasm Inferred from electronic annotation. Source: UniProtKB-KW presynaptic membrane Inferred from electronic annotation. Source: UniProtKB-SubCell
Molecular function	ATP binding Inferred from electronic annotation. Source: UniProtKB-KW calmodulin binding Inferred from electronic annotation. Source: UniProtKB-KW calmodulin-dependent protein kinase activity Inferred from electronic annotation. Source: EC glutamate receptor binding Inferred from physical interaction. Source: MGI
Complete GO annotation...

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With	Entry	#Exp.	IntAct
Camk2b	P28652	2	EBI-400402,EBI-397029
Dlg4	Q62108	1	EBI-400384,EBI-300895
Pdcd6ip	Q9WU78	2	EBI-400402,EBI-641897

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Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Chain

1 – 478

478

Calcium/calmodulin-dependent protein kinase type II subunit alpha

PRO_0000086092

Domain

13 – 271

259

Protein kinase

Nucleotide binding

19 – 27

9

ATP By similarity

Region

290 – 300

11

Calmodulin-binding

Region

310 – 320

11

Interaction with BAALC By similarity

Active site

135

1

Proton acceptor

Binding site

42

1

ATP By similarity

Modified residue

13

1

Phosphotyrosine Ref.8

Modified residue

25

1

Phosphoserine Ref.7

Modified residue

275

1

Phosphoserine Ref.9

Modified residue

286

1

Phosphothreonine; by autocatalysis Ref.9

Modified residue

333

1

Phosphoserine Ref.9 Ref.6

Modified residue

334

1

Phosphothreonine Ref.9

Modified residue

337

1

Phosphothreonine Ref.9

Alternative sequence

1 – 289

289

Missing in isoform Alpha KAP.

VSP_004767

Alternative sequence

290 – 314

25

LKKFN…TRNFS → MLLFLTLWALVPCLVLLTLY FLSST in isoform Alpha KAP.

VSP_004768

Alternative sequence

328

1

K → KKRKSSSSVQLM in isoform Alpha KAP.

VSP_004769

Sequence conflict

40

1

A → P in CAA32946. Ref.1

Sequence conflict

169

1

A → R in CAA32946. Ref.1

Sequence conflict

228

1

G → R in CAA32946. Ref.1

1

.

478

Helix Strand Turn

Details...

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Sequence		Length	Mass (Da)
Isoform Alpha CaMKII [UniParc]. Last modified January 23, 2007. Version 2. Checksum: 306F416CCE9B5F62 Show »	FASTA	478	54,115
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
Isoform Alpha KAP. Checksum: 3FB8D6A5C891CBD4 Show »	FASTA	200	22,584
10 20 30 40 50 60 MLLFLTLWAL VPCLVLLTLY FLSSTGGKSG GNKKNDGVKK RKSSSSVQLM ESSESTNTTI 70 80 90 100 110 120 EDEDTKVRKQ EIIKVTEQLI EAISNGDFES YTKMCDPGMT AFEPEALGNL VEGLDFHRFY 130 140 150 160 170 180 FENLWSRNSK PVHTTILNPH IHLMGDESAC IAYIRITQYL DAGGIPRTAQ SEETRVWHRR 190 200 DGKWQIVHFH RSGAPSVLPH « Hide

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	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Sequence of the cDNA for the alpha subunit of calmodulin kinase II from mouse brain." Hanley R.M., Payne M.E., Cruzalegui F., Christenson M.A., Means A.R. Nucleic Acids Res. 17:3992-3992(1989) [PubMed: 2543961] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA]. Strain: ICR. Tissue: Brain.
[2]	"An alternative, nonkinase product of the brain-specifically expressed Ca2+/calmodulin-dependent kinase II alpha isoform gene in skeletal muscle." Bayer K.-U., Loehler J., Harbers K. Mol. Cell. Biol. 16:29-36(1996) [PubMed: 8524307] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM ALPHA KAP). Strain: BALB/c. Tissue: Skeletal muscle.
[3]	"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: 16141072] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. Strain: C57BL/6J. Tissue: Hippocampus.
[4]	"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)." The MGC Project Team Genome Res. 14:2121-2127(2004) [PubMed: 15489334] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. Tissue: Eye.
[5]	Lubec G., Sunyer B., Chen W.-Q. Submitted (JAN-2009) to UniProtKB Cited for: PROTEIN SEQUENCE OF 9-21; 33-42; 135-146; 260-267; 301-311; 329-344; 353-371; 397-405; 434-445 AND 470-478, MASS SPECTROMETRY. Strain: OF1. Tissue: Hippocampus.
[6]	"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: 15572359] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-333, MASS SPECTROMETRY. Tissue: Brain.
[7]	"Quantitative analysis of both protein expression and serine / threonine post-translational modifications through stable isotope labeling with dithiothreitol." Vosseller K., Hansen K.C., Chalkley R.J., Trinidad J.C., Wells L., Hart G.W., Burlingame A.L. Proteomics 5:388-398(2005) [PubMed: 15648052] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-25, MASS SPECTROMETRY. Tissue: Brain.
[8]	"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: 18034455] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT TYR-13, MASS SPECTROMETRY. Tissue: Brain.
[9]	"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: 17114649] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-275; THR-286; SER-333; THR-334 AND THR-337, MASS SPECTROMETRY. Tissue: Brain cortex.
+	Additional computationally mapped references.

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EMBL
GenBank
DDBJ

X14836 mRNA. Translation: CAA32946.1.
X87142 mRNA. Translation: CAA60620.1.
AK083245 mRNA. Translation: BAC38829.1.
BC031745 mRNA. Translation: AAH31745.1.

IPI

IPI00230096.
IPI00621806.

PIR

JC6083.
S04365.

RefSeq

NP_033922.1.
NP_803126.1.

UniGene

Mm.131530

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
1HKX	X-ray	2.65	A/B/C/D/E/F/G/H/I/J/K/L/M/N	336-478	[»]

SMR

P11798. Positions 10-308.

ModBase

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DIP

DIP-31593N.

IntAct

P11798. 19 interactions.

STRING

P11798.

PhosphoSite

P11798.

PRIDE

P11798.

Ensembl

ENSMUST00000102887; ENSMUSP00000099951; ENSMUSG00000024617; Mus musculus. [Genome view]
ENSMUST00000102888; ENSMUSP00000099952; ENSMUSG00000024617; Mus musculus. [Genome view]
ENSMUST00000115295; ENSMUSP00000110950; ENSMUSG00000024617; Mus musculus. [Genome view]

GeneID

12322.

KEGG

mmu:12322.

UCSC

uc008fbg.1. mouse.
uc008fbh.1. mouse.

CTD

12322.

MGI

MGI:88256. Camk2a.

eggNOG

roNOG13785.

HOVERGEN

P11798.

PhylomeDB

P11798.

BRENDA

2.7.11.17. 244.

ArrayExpress

P11798.

Bgee

P11798.

Genevestigator

P11798.

GermOnline

ENSMUSG00000024617. Mus musculus.

InterPro

IPR020636. Ca/CaM-dep_prot_kinase-like.
IPR015742. Ca/CaM-dep_prot_kinase_2.
IPR011009. Kinase-like_dom.
IPR000719. Prot_kinase_cat_dom.
IPR017441. Protein_kinase_ATP_BS.
IPR017442. Se/Thr_prot_kinase-like_dom.
IPR008271. Ser/Thr_prot_kinase_AS.
IPR002290. Ser/Thr_prot_kinase_dom.
[Graphical view]

PANTHER

PTHR22982. Ca/CaM-dep_prot_kinase-like. 1 hit.
PTHR22982:SF64. CaMKII. 1 hit.

Pfam

PF00069. Pkinase. 1 hit.
[Graphical view]

SMART

SM00220. S_TKc. 1 hit.
[Graphical view]

PROSITE

PS00107. PROTEIN_KINASE_ATP. 1 hit.
PS50011. PROTEIN_KINASE_DOM. 1 hit.
PS00108. PROTEIN_KINASE_ST. 1 hit.
[Graphical view]

ProtoNet

Search...

NextBio

280898.

SOURCE

Search...

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Entry name

KCC2A_MOUSE

Accession

Primary (citable) accession number: P11798
Secondary accession number(s): Q61284, Q6ZWN4

Entry history

Integrated into UniProtKB/Swiss-Prot:	October 1, 1989
Last sequence update:	January 23, 2007
Last modified:	February 9, 2010
This is version 116 of the entry and version 2 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation project

HPI (Human Proteome Initiative)

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MGD cross-references

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

PDB cross-references

Index of Protein Data Bank (PDB) cross-references

Human and mouse protein kinases

Human and mouse protein kinases: classification and index

SIMILARITY comments

Index of protein domains and families

This entry describes 2 isoforms produced by alternative splicing. [Align] [Select]

Isoform Alpha CaMKII (identifier: P11798-1)

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.

Isoform Alpha KAP (identifier: P11798-2)

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

Note: Postsynaptic lipid rafts (By similarity). Has no kinase activity.