P11798 (KCC2A_MOUSE) Reviewed, UniProtKB/Swiss-Prot

Names and origin

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) [Reference proteome]

Taxonomic identifier

10090 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Glires › Rodentia › Sciurognathi › Muroidea › Muridae › Murinae › Mus › Mus

Protein attributes

Sequence length	478 AA.
Sequence status	Complete.
Protein existence	Evidence 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 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.

Ontologies

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 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 calcium ion transport Inferred from mutant phenotype PubMed 12660151. Source: MGI positive regulation of NF-kappaB transcription factor activity Inferred from electronic annotation. Source: Compara protein autophosphorylation Inferred from mutant phenotype PubMed 12660151. Source: MGI regulation of neuronal synaptic plasticity Inferred from mutant phenotype PubMed 17610578. Source: MGI regulation of neurotransmitter secretion Inferred from mutant phenotype PubMed 12629219. Source: MGI
Cellular_component	calcium- and calmodulin-dependent protein kinase complex Traceable author statement PubMed 11264466. Source: UniProtKB cell junction Inferred from electronic annotation. Source: UniProtKB-KW cytoplasm Inferred from electronic annotation. Source: UniProtKB-SubCell plasma membrane 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-dependent protein kinase activity Inferred from electronic annotation. Source: EC protein serine/threonine kinase activity Inferred from direct assay PubMed 18480293. Source: MGI
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
Bag6	Q9Z1R2	3	EBI-400402,EBI-644645
Dlg4	Q62108	3	EBI-400384,EBI-300895

Alternative products

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: Has no kinase activity.

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Chain

1 – 478

478

Calcium/calmodulin-dependent protein kinase type II subunit alpha

PRO_0000086092

Regions

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

Sites

Active site

135

1

Proton acceptor

Binding site

42

1

ATP By similarity

Amino acid modifications

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.6 Ref.9

Modified residue

334

1

Phosphothreonine Ref.9

Modified residue

337

1

Phosphothreonine Ref.9

Natural variations

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

Experimental info

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

Secondary structure

1

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

478

Helix Strand Turn

Details...

Turn

338 – 340

3

Helix

341 – 362

22

Helix

366 – 372

7

Beta strand

373 – 380

8

Helix

382 – 384

3

Beta strand

389 – 392

4

Helix

393 – 400

8

Helix

404 – 406

3

Beta strand

410 – 421

12

Beta strand

423 – 437

15

Beta strand

445 – 458

14

Beta strand

461 – 472

12

Sequences

	Sequence		Length	Mass (Da)
	Isoform Alpha CaMKII [UniParc]. Last modified January 23, 2007. Version 2. Checksum: 306F416CCE9B5F62	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
	Isoform Alpha KAP [UniParc]. Checksum: 3FB8D6A5C891CBD4	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

References

	« 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] [Europe PMC] [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] [Europe PMC] [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. , Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R., Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T., Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A., Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B., Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M., Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S., Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E., Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D., Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M., Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H., Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V., Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S., Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H., Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N., Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F., Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G., Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z., Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C., Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y., Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S., Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K., Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R., van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H., Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M., Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C., Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S., Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K., Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M., Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C., Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A., Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y. Science 309:1559-1563(2005) [PubMed] [Europe PMC] [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] [Europe PMC] [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] [Europe PMC] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-333, MASS SPECTROMETRY. Tissue: Forebrain.
[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] [Europe PMC] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-25, MASS SPECTROMETRY. Strain: C57BL/6. 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] [Europe PMC] [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] [Europe PMC] [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.

Cross-references

Sequence databases

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. NM_009792.3.
NP_803126.1. NM_177407.4.

UniGene

Mm.131530.

3D structure databases

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	[»]

ProteinModelPortal

P11798.

SMR

P11798. Positions 7-474.

ModBase

Search...

Protein-protein interaction databases

DIP

DIP-31593N.

IntAct

P11798. 20 interactions.

MINT

MINT-136541.

PTM databases

PhosphoSite

P11798.

Proteomic databases

PaxDb

P11798.

PRIDE

P11798.

Protocols and materials databases

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENSMUST00000102888; ENSMUSP00000099952; ENSMUSG00000024617.
ENSMUST00000115295; ENSMUSP00000110950; ENSMUSG00000024617.

GeneID

12322.

KEGG

mmu:12322.

UCSC

uc008fbh.2. mouse.

Organism-specific databases

CTD

815.

MGI

MGI:88256. Camk2a.

Phylogenomic databases

eggNOG

COG0515.

GeneTree

ENSGT00680000099653.

HOGENOM

HOG000233016.

HOVERGEN

HBG108055.

KO

K04515.

OrthoDB

EOG42JNR7.

Enzyme and pathway databases

BRENDA

2.7.11.17. 3474.

Gene expression databases

ArrayExpress

P11798.

Bgee

P11798.

Genevestigator

P11798.

GermOnline

ENSMUSG00000024617. 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

P11798.

ChEMBL

CHEMBL3347.

ChiTaRS

CAMK2A. mouse.

EvolutionaryTrace

P11798.

NextBio

280898.

SOURCE

Search...

Entry information

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:	April 3, 2013
This is version 144 of the entry and version 2 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program