CAMK4 - Calcium/calmodulin-dependent protein kinase type IV - human protein (Function)
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CAMK4 »  Calcium/calmodulin-dependent protein kinase type IV   [ EC ]  (CaMK IV)
Protein also known as:  CaM kinase-GR.
Gene name:  CAMK4
Entry whose protein(s) existence is based on evidence at protein level
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Calcium/calmodulin-dependent protein kinase that operates in the calcium-triggered CaMKK-CaMK4 signaling cascade and regulates, mainly by phosphorylation, the activity of several transcription activators, such as CREB1, MEF2D, JUN and RORA, which play pivotal roles in immune response, inflammation, and memory consolidation. In the thymus, regulates the CD4(+)/CD8(+) double positive thymocytes selection threshold during T-cell ontogeny. In CD4 memory T-cells, is required to link T-cell antigen receptor (TCR) signaling to the production of IL2, IFNG and IL4 (through the regulation of CREB and MEF2). Regulates the differentiation and survival phases of osteoclasts and dendritic cells (DCs). Mediates DCs survival by linking TLR4 and the regulation of temporal expression of BCL2. Phosphorylates the transcription activator CREB1 on 'Ser-133' in hippocampal neuron nuclei and contribute to memory consolidation and long term potentiation (LTP) in the hippocampus. Can activate the MAP kinases MAPK1/ERK2, MAPK8/JNK1 and MAPK14/p38 and stimulate transcription through the phosphorylation of ELK1 and ATF2. Can also phosphorylate in vitro CREBBP, PRM2, MEF2A and STMN1/OP18.  
  • CuratedUniProtKB
GO molecular function 
ATP bindingdefinition[GO:0005524]  
  • IEAUniProtKB KW
Calmodulin bindingdefinition[GO:0005516]  
  • IEAUniProtKB KW
Calmodulin-dependent protein kinase activitydefinition[GO:0004683]  
  • IEAEC 2 GO
GO biological process 
Inflammatory responsedefinition[GO:0006954]  
  • IEAUniProtKB KW
Long-term memorydefinition[GO:0007616]  
  • IGIUniProtKB
Not  Myeloid dendritic cell cytokine productiondefinition[GO:0002372]  
  • IMPUniProtKB
Myeloid dendritic cell differentiationdefinition[GO:0043011]  
  • IMPUniProtKB
Neuron-neuron synaptic transmissiondefinition[GO:0007270] silver  
  • IEAOrtholog Compara
Nucleocytoplasmic transportdefinition[GO:0006913] silver  
  • IEAOrtholog Compara
Positive regulation of protein export from nucleusdefinition[GO:0046827] silver  
  • IEAOrtholog Compara
Positive regulation of transcription, DNA-templateddefinition[GO:0045893]  
  • IDAUniProtKB
Protein phosphorylationdefinition[GO:0006468] silver  
  • IEAOrtholog Compara
Regulation of osteoclast differentiationdefinition[GO:0045670]  
  • TASUniProtKB
Regulation of T cell differentiation in thymusdefinition[GO:0033081]  
  • TASUniProtKB
Enzymatic activity 
This protein acts as an enzyme. It is known to catalyze the following reaction
EC ATP + a protein ADP + a phosphoprotein.  
  • CuratedUniProtKB
It is regulated in the following manner
Activated by Ca(2+)/calmodulin. Binding of calmodulin results in conformational change that relieves intrasteric autoinhibition and allows phosphorylation of Thr-200 within the activation loop by CaMKK1 or CaMKK2. Phosphorylation of Thr-200 results in a 10-20-fold increase in total activity to generate Ca(2+)/calmodulin-independent activity. Autophosphorylation of the N-terminus Ser-12 and Ser-13 is required for full activation. Inactivated by protein phosphatase 2A (PPP2CA/PPP2CB) which dephosphorylates Thr-200, thereby terminating autonomous activity and helping to maintain the enzyme in its autoinhibited state.  
  • CuratedUniProtKB
More information is available from:
According to KEGG, this protein belongs to the following pathways:
Calcium signaling pathway  hsa04020+814  
Cholinergic synapse  hsa04725+814  
Long-term potentiation  hsa04720+814  
Neurotrophin signaling pathway  hsa04722+814  
Osteoclast differentiation  hsa04380+814  
According to Reactome, this protein belongs to the following pathways:
Activation of CaMK IV  REACT_20652  
CaMK IV-mediated phosphorylation of CREB  REACT_15502  
CREB phosphorylation through the activation of CaMKK  REACT_20661  
Transcriptional activation of mitochondrial biogenesis  REACT_200608  


Biological process 
Adaptive immunity  definition   [KW-1064]
Immunity  definition   [KW-0391]
Inflammatory response  definition   [KW-0395]
Molecular function 
Kinase  definition   [KW-0418]
Serine/threonine-protein kinase  definition   [KW-0723]
Transferase  definition   [KW-0808]
Technical term 
Reference proteome  definition   [KW-1185]

Further external links

GeneWiki: CAMK4
GenomeRNAi: 814
PRO: PR:Q16566