CAMK4

The product of this gene belongs to the serine/threonine protein kinase family, and to the Ca(2+)/calmodulin-dependent protein kinase subfamily. This enzyme is a multifunctional serine/threonine protein kinase with limited tissue distribution, that has been implicated in transcriptional regulation in lymphocytes, neurons and male germ cells. [provided by RefSeq, Jul 2008]

Calcium/Calmodulin Dependent Protein Kinase IV

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.

Adaptive immune response Source: UniProtKB-KW
Chemical synaptic transmission Source: Reactome
Inflammatory response Source: UniProtKB-KW
Intracellular signal transduction Source: GO_Central
Long-term memory Source: UniProtKB
Myeloid dendritic cell differentiation Source: UniProtKB
Peptidyl-serine phosphorylation Source: GO_Central
Positive regulation of transcription, DNA-templated Source: UniProtKB
Protein autophosphorylation Source: GO_Central
Protein phosphorylation Source: ProtInc
Regulation of osteoclast differentiation Source: UniProtKB
Regulation of T cell differentiation in thymus Source: UniProtKB
Signal transduction Source: ProtInc

Nucleus; Cytoplasm. Localized in hippocampal neuron nuclei. In spermatids, associated with chromatin and nuclear matrix (By similarity).

Phosphorylated by CaMKK1 and CaMKK2 on Thr-200. Dephosphorylated by protein phosphatase 2A. Autophosphorylated on Ser-12 and Ser-13.
Glycosylation at Ser-189 modulates the phosphorylation of CaMK4 at Thr-200 and negatively regulates its activity toward CREB1 in basal conditions and during early inomycin stimulation.