Reviewed, UniProtKB/Swiss-Prot Q9UQM7 (KCC2A_HUMAN)

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
Synonyms:	CAMKA, KIAA0968

Organism

Homo sapiens (Human) [Complete proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo

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. Ref.3
Subcellular location	Cell junction › synapse › presynaptic cell membrane By similarity. Cell junction › synapse By similarity. Note: Postsynaptic lipid rafts By similarity.
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 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
Gene Ontology (GO)
Biological process	positive regulation of NF-kappaB transcription factor activity Inferred from mutant phenotype. Source: UniProtKB protein amino acid phosphorylation Inferred from direct assay. Source: UniProtKB
Cellular component	cell junction Inferred from electronic annotation. Source: UniProtKB-KW cytosol Inferred from Experiment. Source: Reactome endocytic vesicle membrane Inferred from Experiment. Source: Reactome nucleoplasm Inferred from Experiment. Source: Reactome 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
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
CALM1	P62158	1	EBI-1383687,EBI-397435
CAMK2D	Q13557	1	EBI-1383687,EBI-351018
CHMP5	Q9NZZ3	1	EBI-1383687,EBI-751303
DLG3	Q92796	1	EBI-1383687,EBI-80440

Alternative products

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

Isoform A (identifier: Q9UQM7-1)

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 B (identifier: Q9UQM7-2)

The sequence of this isoform differs from the canonical sequence as follows:
     328-328: K → KKRKSSSSVQLM

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_0000086091

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 By similarity

Binding site

42

1

ATP By similarity

Amino acid modifications

Modified residue

13

1

Phosphotyrosine By similarity

Modified residue

25

1

Phosphoserine By similarity

Modified residue

275

1

Phosphoserine By similarity

Modified residue

286

1

Phosphothreonine; by autocatalysis By similarity

Modified residue

333

1

Phosphoserine By similarity

Modified residue

334

1

Phosphothreonine By similarity

Modified residue

337

1

Phosphothreonine By similarity

Natural variations

Alternative sequence

328

1

K → KKRKSSSSVQLM in isoform B.

VSP_004766

Experimental info

Sequence conflict

365

1

G → D in BAA76812. Ref.2

Secondary structure

1

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478

Helix Strand Turn

Details...

Beta strand

13 – 18

6

Beta strand

26 – 32

7

Beta strand

38 – 44

7

Helix

46 – 48

3

Helix

51 – 66

16

Beta strand

75 – 80

6

Beta strand

85 – 90

6

Helix

97 – 102

6

Helix

109 – 128

20

Helix

138 – 140

3

Beta strand

141 – 144

4

Beta strand

152 – 154

3

Helix

182 – 185

4

Helix

193 – 198

6

Helix

202 – 207

6

Helix

218 – 226

9

Helix

236 – 239

4

Helix

242 – 251

10

Turn

256 – 258

3

Helix

262 – 265

4

Helix

269 – 272

4

Helix

274 – 277

4

Helix

284 – 298

15

Sequences

	Sequence		Length	Mass (Da)
	Isoform A [UniParc]. Last modified May 1, 2000. Version 1. Checksum: 10800A85CAD724BB	FASTA	478	54,030
	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 NKKSDGVKES SESTNTTIED EDTKVRKQEI IKVTEQLIEA 370 380 390 400 410 420 ISNGGFESYT KMCDPGMTAF EPEALGNLVE GLDFHRFYFE NLWSRNSKPV HTTILNPHIH 430 440 450 460 470 LMGDESACIA YIRITQYLDA GGIPRTAQSE ETRVWHRRDG KWQIVHFHRS GAPSVLPH
	Isoform B. Checksum: 71E73338CE86A2F2	FASTA	489	55,262
	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 NKKSDGVKKR KSSSSVQLME SSESTNTTIE DEDTKVRKQE 370 380 390 400 410 420 IIKVTEQLIE AISNGGFESY TKMCDPGMTA FEPEALGNLV EGLDFHRFYF ENLWSRNSKP 430 440 450 460 470 480 VHTTILNPHI HLMGDESACI AYIRITQYLD AGGIPRTAQS EETRVWHRRD GKWQIVHFHR SGAPSVLPH

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Human calcium/calmodulin-dependent protein kinase II: cDNA cloning and gene analysis." Li G.Y., Cooper N.G.F. Submitted (APR-1999) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS A AND B). Tissue: Brain.
[2]	"Prediction of the coding sequences of unidentified human genes. XIII. The complete sequences of 100 new cDNA clones from brain which code for large proteins in vitro." Nagase T., Ishikawa K., Suyama M., Kikuno R., Hirosawa M., Miyajima N., Tanaka A., Kotani H., Nomura N., Ohara O. DNA Res. 6:63-70(1999) [PubMed: 10231032] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. Tissue: Brain.
[3]	"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: 15312654] [Abstract] Cited for: INTERACTION WITH MPDZ.
+	Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ

AF145710 mRNA. Translation: AAD30558.1.
AF145711 mRNA. Translation: AAD30559.1.
AB023185 mRNA. Translation: BAA76812.1. Different initiation.

IPI

IPI00215715.
IPI00550056.

RefSeq

NP_741960.1.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
2VZ6	X-ray	2.30	A/B	13-302	[»]

SMR

Q9UQM7. Positions 336-474.

ModBase

Search...

Protein-protein interaction databases

IntAct

Q9UQM7. 11 interactions.

STRING

Q9UQM7.

PTM databases

PhosphoSite

Q9UQM7.

Proteomic databases

PRIDE

Q9UQM7.

Genome annotation databases

Ensembl

ENST00000348628; ENSP00000261793; ENSG00000070808; Homo sapiens. [Genome view]

GeneID

815.

Organism-specific databases

CTD

815.

GeneCards

GC05M149579.

HGNC

HGNC:1460. CAMK2A.

HPA

CAB004330.

MIM

114078. gene.

PharmGKB

PA90.

HUGE

Search...

GenAtlas

Search...

Phylogenomic databases

HOVERGEN

Q9UQM7.

PhylomeDB

Q9UQM7.

Enzyme and pathway databases

BRENDA

2.7.11.17. 247.

Pathway_Interaction_DB

fgf_pathway. FGF signaling pathway.
ifngpathway. IFN-gamma pathway.
wnt_calcium_pathway. Noncanonical Wnt signaling pathway.
tgfbrpathway. TGF-beta receptor signaling.
pi3kplctrkpathway. Trk receptor signaling mediated by PI3K and PLC-gamma.

Reactome

REACT_13685. Synaptic Transmission.

Gene expression databases

ArrayExpress

Q9UQM7.

Bgee

Q9UQM7.

CleanEx

HS_CAMK2A.

Genevestigator

Q9UQM7.

Family and domain databases

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...

Other Resources

NextBio

3304.

SOURCE

Search...

Entry information

Entry name

KCC2A_HUMAN

Accession

Primary (citable) accession number: Q9UQM7
Secondary accession number(s): Q9UL21, Q9Y2H4, Q9Y352

Entry history

Integrated into UniProtKB/Swiss-Prot:	April 16, 2002
Last sequence update:	May 1, 2000
Last modified:	February 9, 2010
This is version 92 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation project

HPI (Human Proteome Initiative)

Disclaimer

Any medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.