Names & Taxonomy
- Uniprot ID:
- Q16566
- Entry Name:
- KCC4_HUMAN
- Status:
- reviewed
- Protein Names:
- Calcium/calmodulin-dependent protein kinase type IV (CaMK IV) (EC 2.7.11.17) (CaM kinase-GR)
- Gene Names:
- CAMK4 CAMK CAMK-GR CAMKIV
- Gene Names Primary:
- CAMK4
- Organism:
- Homo sapiens (Human)
Structure
- Length:
- 473
- Sequence:
- MLKVTVPSCSASSCSSVTASAAPGTASLVPDYWIDGSNRDALSDFFEVESELGRGATSIVYRCKQKGTQKPYALKVLKKTVDKKIVRTEIGVLLRLSHPNIIKLKEIFETPTEISLVLELVTGGELFDRIVEKGYYSERDAADAVKQILEAVAYLHENGIVHRDLKPENLLYATPAPDAPLKIADFGLSKIVEHQVLMKTVCGTPGYCAPEILRGCAYGPEVDMWSVGIITYILLCGFEPFYDERGDQFMFRRILNCEYYFISPWWDEVSLNAKDLVRKLIVLDPKKRLTTFQALQHPWVTGKAANFVHMDTAQKKLQEFNARRKLKAAVKAVVASSRLGSASSSHGSIQESHKASRDPSPIQDGNEDMKAIPEGEKIQGDGAQAAVKGAQAELMKVQALEKVKGADINAEEAPKMVPKAVEDGIKVADLELEEGLAEEKLKTVEEAAAPREGQGSSAVGFEVPQQDVILPEY
- Proteomes:
- UP000005640
Subcellular location
- Subcellular Location:
- Cytoplasm. Nucleus. Note=Localized in hippocampal neuron nuclei. In spermatids, associated with chromatin and nuclear matrix (By similarity).
Function
- Function:
- 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.
- Catalytic Activity:
- ATP + a protein = ADP + a phosphoprotein.
- Enzyme Regulation:
- ENZYME REGULATION: 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.
- Active Site:
- ACT_SITE 164 164 Proton acceptor.
- Gene Ontology Go:
- cytoplasm
cytosol
extracellular exosome
nucleolus
nucleoplasm
ATP binding
calcium-dependent protein serine/threonine kinase activity
calmodulin binding
calmodulin-dependent protein kinase activity
activation of phospholipase C activity
adaptive immune response
epidermal growth factor receptor signaling pathway
fibroblast growth factor receptor signaling pathway
inflammatory response
innate immune response
intracellular signal transduction
long-term memory
myeloid dendritic cell differentiation
neurotrophin TRK receptor signaling pathway
peptidyl-serine phosphorylation
positive regulation of transcription, DNA-templated
protein autophosphorylation
protein phosphorylation
regulation of osteoclast differentiation
regulation of T cell differentiation in thymus
signal transduction
synaptic transmission - Gene Ontology Biological Process:
- activation of phospholipase C activity
adaptive immune response
epidermal growth factor receptor signaling pathway
fibroblast growth factor receptor signaling pathway
inflammatory response
innate immune response
intracellular signal transduction
long-term memory
myeloid dendritic cell differentiation
neurotrophin TRK receptor signaling pathway
peptidyl-serine phosphorylation
positive regulation of transcription, DNA-templated
protein autophosphorylation
protein phosphorylation
regulation of osteoclast differentiation
regulation of T cell differentiation in thymus
signal transduction
synaptic transmission - Gene Ontology Molecular Function:
- ATP binding
calcium-dependent protein serine/threonine kinase activity
calmodulin binding
calmodulin-dependent protein kinase activity - Gene Ontology Cellular Component:
- cytoplasm
cytosol
extracellular exosome
nucleolus
nucleoplasm - Keywords:
- 3D-structure
ATP-binding
Adaptive immunity
Calcium
Calmodulin-binding
Complete proteome
Cytoplasm
Glycoprotein
Immunity
Inflammatory response
Kinase
Nucleotide-binding
Nucleus
Phosphoprotein
Polymorphism
Reference proteome
Serine/threonine-protein kinase
Transferase