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Q9UQM7 (KCC2A_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified July 9, 2014. Version 136. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (5) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Interactions·Alt products·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
Synonyms:CAMKA, KIAA0968
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

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 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.4

Subcellular location

Cell junctionsynapsepresynaptic cell membrane By similarity. Cell junctionsynapse 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.

Sequence caution

The sequence BAA76812.1 differs from that shown. Reason: Erroneous initiation. Translation N-terminally shortened.

Ontologies

Keywords
   Cellular componentCell junction
Cell membrane
Membrane
Synapse
   Coding sequence diversityAlternative splicing
   LigandATP-binding
Calmodulin-binding
Nucleotide-binding
   Molecular functionKinase
Serine/threonine-protein kinase
Transferase
   PTMPhosphoprotein
   Technical term3D-structure
Complete proteome
Reference proteome
Gene Ontology (GO)
   Biological_processG1/S transition of mitotic cell cycle

Inferred from electronic annotation. Source: Ensembl

calcium ion transport

Inferred from electronic annotation. Source: Ensembl

cytokine-mediated signaling pathway

Traceable author statement. Source: Reactome

interferon-gamma-mediated signaling pathway

Traceable author statement. Source: Reactome

positive regulation of NF-kappaB transcription factor activity

Inferred from mutant phenotype PubMed 17052756. Source: UniProtKB

protein autophosphorylation

Inferred from electronic annotation. Source: Ensembl

protein phosphorylation

Inferred from direct assay PubMed 17052756. Source: UniProtKB

regulation of neuronal synaptic plasticity

Inferred from electronic annotation. Source: Ensembl

regulation of neurotransmitter secretion

Inferred from electronic annotation. Source: Ensembl

synaptic transmission

Traceable author statement. Source: Reactome

   Cellular_componentcell junction

Inferred from electronic annotation. Source: UniProtKB-KW

cytosol

Traceable author statement. Source: Reactome

endocytic vesicle membrane

Traceable author statement. Source: Reactome

nucleoplasm

Traceable author statement. Source: Reactome

nucleus

Inferred from direct assay PubMed 21630459. Source: UniProt

plasma membrane

Traceable author statement. Source: Reactome

presynaptic membrane

Inferred from electronic annotation. Source: UniProtKB-SubCell

   Molecular_functionATP binding

Inferred from electronic annotation. Source: UniProtKB-KW

calmodulin-dependent protein kinase activity

Inferred from electronic annotation. Source: UniProtKB-EC

kinase activity

Inferred from direct assay PubMed 17052756. Source: UniProtKB

protein binding

Inferred from physical interaction PubMed 17052756. Source: UniProtKB

Complete GO annotation...

Binary interactions

With

Entry

#Exp.

IntAct

Notes

GRIN2BQ132243EBI-1383687,EBI-2256942

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 keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 478478Calcium/calmodulin-dependent protein kinase type II subunit alpha
PRO_0000086091

Regions

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

Sites

Active site1351Proton acceptor By similarity
Binding site421ATP By similarity

Amino acid modifications

Modified residue131Phosphotyrosine By similarity
Modified residue2861Phosphothreonine; by autocatalysis By similarity

Natural variations

Alternative sequence3281K → KKRKSSSSVQLM in isoform B.
VSP_004766

Experimental info

Sequence conflict3651D → G in AAD30558. Ref.1
Sequence conflict3651D → G in AAD30559. Ref.1

Secondary structure

.............................................. 478
Helix Strand Turn

Details...

Sequences

Sequence LengthMass (Da)Tools
Isoform A [UniParc].

Last modified May 18, 2010. Version 2.
Checksum: 208143A311BA9262

FASTA47854,088
        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 
ISNGDFESYT KMCDPGMTAF EPEALGNLVE GLDFHRFYFE NLWSRNSKPV HTTILNPHIH 

       430        440        450        460        470 
LMGDESACIA YIRITQYLDA GGIPRTAQSE ETRVWHRRDG KWQIVHFHRS GAPSVLPH 

« Hide

Isoform B [UniParc].

Checksum: 41E67A1E15EB142B
Show »

FASTA48955,320

References

« Hide '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] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
Tissue: Brain.
[3]"The DNA sequence and comparative analysis of human chromosome 5."
Schmutz J., Martin J., Terry A., Couronne O., Grimwood J., Lowry S., Gordon L.A., Scott D., Xie G., Huang W., Hellsten U., Tran-Gyamfi M., She X., Prabhakar S., Aerts A., Altherr M., Bajorek E., Black S. expand/collapse author list , Branscomb E., Caoile C., Challacombe J.F., Chan Y.M., Denys M., Detter J.C., Escobar J., Flowers D., Fotopulos D., Glavina T., Gomez M., Gonzales E., Goodstein D., Grigoriev I., Groza M., Hammon N., Hawkins T., Haydu L., Israni S., Jett J., Kadner K., Kimball H., Kobayashi A., Lopez F., Lou Y., Martinez D., Medina C., Morgan J., Nandkeshwar R., Noonan J.P., Pitluck S., Pollard M., Predki P., Priest J., Ramirez L., Retterer J., Rodriguez A., Rogers S., Salamov A., Salazar A., Thayer N., Tice H., Tsai M., Ustaszewska A., Vo N., Wheeler J., Wu K., Yang J., Dickson M., Cheng J.-F., Eichler E.E., Olsen A., Pennacchio L.A., Rokhsar D.S., Richardson P., Lucas S.M., Myers R.M., Rubin E.M.
Nature 431:268-274(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[4]"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 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.
AC011372 Genomic DNA. No translation available.
CCDSCCDS43386.1. [Q9UQM7-1]
CCDS43387.1. [Q9UQM7-2]
RefSeqNP_741960.1. NM_171825.2. [Q9UQM7-1]
UniGeneHs.743976.

3D structure databases

PDBe
RCSB-PDB
PDBj
EntryMethodResolution (Å)ChainPositionsPDBsum
2VZ6X-ray2.30A/B13-302[»]
3SOAX-ray3.55A1-474[»]
ProteinModelPortalQ9UQM7.
SMRQ9UQM7. Positions 7-474.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid107265. 36 interactions.
DIPDIP-39705N.
IntActQ9UQM7. 7 interactions.
MINTMINT-95446.
STRING9606.ENSP00000381412.

Chemistry

BindingDBQ9UQM7.
ChEMBLCHEMBL2097164.
GuidetoPHARMACOLOGY1555.

PTM databases

PhosphoSiteQ9UQM7.

Polymorphism databases

DMDM296434552.

Proteomic databases

MaxQBQ9UQM7.
PaxDbQ9UQM7.
PRIDEQ9UQM7.

Protocols and materials databases

DNASU815.
StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000348628; ENSP00000261793; ENSG00000070808. [Q9UQM7-1]
ENST00000398376; ENSP00000381412; ENSG00000070808. [Q9UQM7-2]
GeneID815.
KEGGhsa:815.
UCSCuc003lru.2. human. [Q9UQM7-1]

Organism-specific databases

CTD815.
GeneCardsGC05M149579.
HGNCHGNC:1460. CAMK2A.
HPACAB004330.
MIM114078. gene.
neXtProtNX_Q9UQM7.
PharmGKBPA90.
HUGESearch...
GenAtlasSearch...

Phylogenomic databases

eggNOGCOG0515.
HOGENOMHOG000233016.
HOVERGENHBG108055.
KOK04515.
OMAITCTRFS.
OrthoDBEOG7ZD1VM.
PhylomeDBQ9UQM7.
TreeFamTF315229.

Enzyme and pathway databases

BRENDA2.7.11.17. 2681.
ReactomeREACT_111102. Signal Transduction.
REACT_120956. Cellular responses to stress.
REACT_13685. Neuronal System.
REACT_6900. Immune System.
SignaLinkQ9UQM7.

Gene expression databases

ArrayExpressQ9UQM7.
BgeeQ9UQM7.
CleanExHS_CAMK2A.
GenevestigatorQ9UQM7.

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

ChiTaRSCAMK2A. human.
EvolutionaryTraceQ9UQM7.
GeneWikiCAMK2A.
GenomeRNAi815.
NextBio3304.
PROQ9UQM7.
SOURCESearch...

Entry information

Entry nameKCC2A_HUMAN
AccessionPrimary (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 18, 2010
Last modified: July 9, 2014
This is version 136 of the entry and version 2 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny 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.

Relevant documents

SIMILARITY comments

Index of protein domains and families

Human and mouse protein kinases

Human and mouse protein kinases: classification and index

PDB cross-references

Index of Protein Data Bank (PDB) cross-references

MIM cross-references

Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

Human chromosome 5

Human chromosome 5: entries, gene names and cross-references to MIM