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Protein

Calcium/calmodulin-dependent protein kinase type II subunit alpha

Gene

CAMK2A

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: -Experimental evidence at protein leveli

Functioni

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). Phosphorylates transcription factor FOXO3 on 'Ser-298' (PubMed:23805378). Activates FOXO3 transcriptional activity (By similarity).By similarity1 Publication

Catalytic activityi

ATP + a protein = ADP + a phosphoprotein.1 Publication

Cofactori

Mg2+1 Publication

Enzyme regulationi

Autophosphorylation of Thr-286 allows the kinase to switch from a calmodulin-dependent to a calmodulin-independent state.By similarity

Sites

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

Regions

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

GO - Molecular functioni

  • ATP binding Source: UniProtKB-KW
  • calcium-dependent protein serine/threonine kinase activity Source: UniProtKB
  • calmodulin binding Source: BHF-UCL
  • calmodulin-dependent protein kinase activity Source: UniProtKB
  • glutamate receptor binding Source: ParkinsonsUK-UCL
  • identical protein binding Source: IntAct
  • kinase activity Source: UniProtKB
  • metal ion binding Source: UniProtKB-KW
  • protein homodimerization activity Source: BHF-UCL
  • protein serine/threonine kinase activity Source: ParkinsonsUK-UCL
  • Ras guanyl-nucleotide exchange factor activity Source: Reactome

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 2681
ReactomeiR-HSA-3371571 HSF1-dependent transactivation
R-HSA-399719 Trafficking of AMPA receptors
R-HSA-4086398 Ca2+ pathway
R-HSA-438066 Unblocking of NMDA receptor, glutamate binding and activation
R-HSA-442729 CREB phosphorylation through the activation of CaMKII
R-HSA-442742 CREB phosphorylation through the activation of Ras
R-HSA-442982 Ras activation upon Ca2+ influx through NMDA receptor
R-HSA-5576892 Phase 0 - rapid depolarisation
R-HSA-5578775 Ion homeostasis
R-HSA-5673001 RAF/MAP kinase cascade
R-HSA-877300 Interferon gamma signaling
R-HSA-936837 Ion transport by P-type ATPases
SignaLinkiQ9UQM7
SIGNORiQ9UQM7

Names & Taxonomyi

Protein namesi
Recommended name:
Calcium/calmodulin-dependent protein kinase type II subunit alpha (EC:2.7.11.171 Publication)
Short name:
CaM kinase II subunit alpha
Short name:
CaMK-II subunit alpha
Gene namesi
Name:CAMK2A
Synonyms:CAMKA, KIAA0968
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 5

Organism-specific databases

EuPathDBiHostDB:ENSG00000070808.15
HGNCiHGNC:1460 CAMK2A
MIMi114078 gene
neXtProtiNX_Q9UQM7

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, Membrane, Synapse

Pathology & Biotechi

Organism-specific databases

DisGeNETi815
MalaCardsiCAMK2A
OpenTargetsiENSG00000070808
PharmGKBiPA90

Chemistry databases

ChEMBLiCHEMBL4147
DrugBankiDB04119 Hexatantalum Dodecabromide
GuidetoPHARMACOLOGYi1555

Polymorphism and mutation databases

BioMutaiCAMK2A
DMDMi296434552

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00000860911 – 478Calcium/calmodulin-dependent protein kinase type II subunit alphaAdd BLAST478

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei13PhosphotyrosineBy similarity1
Modified residuei257PhosphoserineBy similarity1
Modified residuei286Phosphothreonine; by autocatalysisBy similarity1
Modified residuei330PhosphoserineBy similarity1
Modified residuei331PhosphoserineBy similarity1
Modified residuei333PhosphoserineBy similarity1
Modified residuei336PhosphothreonineBy similarity1
Modified residuei337PhosphothreonineBy similarity1
Modified residuei404PhosphoserineBy similarity1

Keywords - PTMi

Phosphoprotein

Proteomic databases

EPDiQ9UQM7
PaxDbiQ9UQM7
PeptideAtlasiQ9UQM7
PRIDEiQ9UQM7
ProteomicsDBi85559
85560 [Q9UQM7-2]

PTM databases

iPTMnetiQ9UQM7
PhosphoSitePlusiQ9UQM7

Expressioni

Gene expression databases

BgeeiENSG00000070808
CleanExiHS_CAMK2A
ExpressionAtlasiQ9UQM7 baseline and differential
GenevisibleiQ9UQM7 HS

Organism-specific databases

HPAiCAB004330
HPA051783
HPA051785
HPA053973

Interactioni

Subunit structurei

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. Interacts with SYNPO2 (By similarity).By similarity

Binary interactionsi

Show more details

GO - Molecular functioni

  • calmodulin binding Source: BHF-UCL
  • glutamate receptor binding Source: ParkinsonsUK-UCL
  • identical protein binding Source: IntAct
  • protein homodimerization activity Source: BHF-UCL
  • Ras guanyl-nucleotide exchange factor activity Source: Reactome

Protein-protein interaction databases

BioGridi107265, 57 interactors
CORUMiQ9UQM7
DIPiDIP-39705N
IntActiQ9UQM7, 58 interactors
MINTiQ9UQM7
STRINGi9606.ENSP00000381412

Chemistry databases

BindingDBiQ9UQM7

Structurei

Secondary structure

1478
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Helixi9 – 12Combined sources4
Beta strandi13 – 20Combined sources8
Beta strandi26 – 32Combined sources7
Helixi33 – 35Combined sources3
Beta strandi37 – 45Combined sources9
Helixi46 – 48Combined sources3
Helixi51 – 66Combined sources16
Beta strandi75 – 80Combined sources6
Beta strandi82 – 90Combined sources9
Helixi97 – 102Combined sources6
Helixi109 – 128Combined sources20
Helixi138 – 140Combined sources3
Beta strandi141 – 144Combined sources4
Beta strandi152 – 154Combined sources3
Helixi177 – 179Combined sources3
Helixi182 – 185Combined sources4
Helixi193 – 208Combined sources16
Helixi218 – 227Combined sources10
Helixi236 – 239Combined sources4
Helixi242 – 251Combined sources10
Turni256 – 258Combined sources3
Helixi262 – 265Combined sources4
Helixi269 – 272Combined sources4
Helixi274 – 277Combined sources4
Helixi284 – 298Combined sources15
Helixi345 – 362Combined sources18
Helixi366 – 371Combined sources6
Beta strandi373 – 380Combined sources8
Helixi382 – 384Combined sources3
Beta strandi389 – 392Combined sources4
Helixi393 – 400Combined sources8
Helixi402 – 405Combined sources4
Beta strandi411 – 421Combined sources11
Beta strandi426 – 438Combined sources13
Beta strandi440 – 442Combined sources3
Beta strandi444 – 458Combined sources15
Beta strandi461 – 470Combined sources10

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
2VZ6X-ray2.30A/B13-302[»]
3SOAX-ray3.55A1-474[»]
5IG3X-ray2.75A/B/C/D/E/F345-475[»]
ProteinModelPortaliQ9UQM7
SMRiQ9UQM7
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiQ9UQM7

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
InParanoidiQ9UQM7
KOiK04515
OMAiICTRFTE
PhylomeDBiQ9UQM7
TreeFamiTF315229

Family and domain databases

InterProiView protein in InterPro
IPR013543 Ca/CaM-dep_prot_kinase-assoc
IPR011009 Kinase-like_dom_sf
IPR032710 NTF2-like_dom_sf
IPR000719 Prot_kinase_dom
IPR017441 Protein_kinase_ATP_BS
IPR008271 Ser/Thr_kinase_AS
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

Isoform A (identifier: Q9UQM7-1) [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 NKKSDGVKES 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):54,088
Last modified:May 18, 2010 - v2
Checksum:i208143A311BA9262
GO
Isoform B (identifier: Q9UQM7-2) [UniParc]FASTAAdd to basket

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

Show »
Length:489
Mass (Da):55,320
Checksum:i41E67A1E15EB142B
GO

Sequence cautioni

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

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti365D → G in AAD30558 (Ref. 1) Curated1
Sequence conflicti365D → G in AAD30559 (Ref. 1) Curated1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_004766328K → KKRKSSSSVQLM in isoform B. 1 Publication1

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF145710 mRNA Translation: AAD30558.1
AF145711 mRNA Translation: AAD30559.1
AB023185 mRNA Translation: BAA76812.1 Different initiation.
AC011372 Genomic DNA No translation available.
CCDSiCCDS43386.1 [Q9UQM7-1]
CCDS43387.1 [Q9UQM7-2]
RefSeqiNP_741960.1, NM_171825.2 [Q9UQM7-1]
UniGeneiHs.743976

Genome annotation databases

EnsembliENST00000348628; ENSP00000261793; ENSG00000070808 [Q9UQM7-1]
ENST00000398376; ENSP00000381412; ENSG00000070808 [Q9UQM7-2]
GeneIDi815
KEGGihsa:815
UCSCiuc003lrt.3 human [Q9UQM7-1]

Keywords - Coding sequence diversityi

Alternative splicing

Similar proteinsi

Entry informationi

Entry nameiKCC2A_HUMAN
AccessioniPrimary (citable) accession number: Q9UQM7
Secondary accession number(s): Q9UL21, Q9Y2H4, Q9Y352
Entry historyiIntegrated into UniProtKB/Swiss-Prot: April 16, 2002
Last sequence update: May 18, 2010
Last modified: June 20, 2018
This is version 175 of the entry and version 2 of the sequence. See complete history.
Entry statusiReviewed (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.

Miscellaneousi

Keywords - Technical termi

3D-structure, Complete proteome, Reference proteome

Documents

  1. Human chromosome 5
    Human chromosome 5: entries, gene names and cross-references to MIM
  2. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  3. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  4. Human and mouse protein kinases
    Human and mouse protein kinases: classification and index
  5. SIMILARITY comments
    Index of protein domains and families

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