P08414
uniprot
P08414
canonical
activity_regulation
ACTIVITY REGULATION: Activated by Ca(2+)/calmodulin. Binding of calmodulin results in conformational change that relieves intrasteric autoinhibition and allows phosphorylation of Thr-196 within the activation loop by CaMKK1 or CaMKK2. Phosphorylation of Thr-196 results in a 10-20-fold increase in total activity to generate Ca(2+)/calmodulin-independent activity. Autophosphorylation of the N-terminus Ser-11 and Ser-12 is required for full activation. Inactivated by protein phosphatase 2A (PPP2CA/PPP2CB) which dephosphorylates Thr-196, thereby terminating autonomous activity and helping to maintain the enzyme in its autoinhibited state.
uniprot
proteins
amino_acid_sequence
MLKVTVPSCPSSPCSSVTASTENLVPDYWIDGSNRDPLGDFFEVESELGRGATSIVYRCKQKGTQKPYALKVLKKTVDKKIVRTEIGVLLRLSHPNIIKLKEIFETPTEISLVLELVTGGELFDRIVEKGYYSERDARDAVKQILEAVAYLHENGIVHRDLKPENLLYATPAPDAPLKIADFGLSKIVEHQVLMKTVCGTPGYCAPEILRGCAYGPEVDMWSVGIITYILLCGFEPFYDERGDQFMFRRILNCEYYFISPWWDEVSLNAKDLVKKLIVLDPKKRLTTFQALQHPWVTGKAANFVHMDTAQKKLQEFNARRKLKAAVKAVVASSRLGSASSSHTSIQENHKASSDPPSTQDAKDSTDLLGKKMQEEDQEEDQVEAEASADEMRKLQSEEVEKDAGVKEEETSSMVPQDPEDELETDDPEMKRDSEEKLKSVEEEMDPMTEEEAPDAGLGVPQQDAIQPEY
uniprot
proteins
ec_number
2.7.11.17
uniprot
proteins
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 (By similarity). May be involved in spermatogenesis. {ECO:0000250, ECO:0000269|PubMed:10932193, ECO:0000269|PubMed:11572782, ECO:0000269|PubMed:18829949, ECO:0000269|PubMed:8195196, ECO:0000269|PubMed:9727976}.
uniprot
proteins
mass_dalton
52628
uniprot
proteins
post_translational_modification
PTM: Phosphorylated by CaMKK1 and CaMKK2 on Thr-196. Dephosphorylated by protein phosphatase 2A. Autophosphorylated on Ser-11 and Ser-12 (By similarity). {ECO:0000250}.; PTM: Glycosylation at Ser-185 modulates the phosphorylation of CaMK4 at Thr-196 and negatively regulates its activity toward CREB1 in basal conditions and during early inomycin stimulation. {ECO:0000250}.
uniprot
proteins
protein_family
CAMK Ser/Thr protein kinase family
uniprot
proteins
protein_family
CaMK subfamily
uniprot
proteins
protein_family
Protein kinase superfamily
uniprot
proteins
pubmed
10932193
uniprot
proteins
pubmed
11572782
uniprot
proteins
pubmed
11951046
uniprot
proteins
pubmed
18829949
uniprot
proteins
pubmed
1893997
uniprot
proteins
pubmed
21183079
uniprot
proteins
pubmed
2536634
uniprot
proteins
pubmed
3033675
uniprot
proteins
pubmed
8195196
uniprot
proteins
pubmed
9727976
uniprot
proteins
sequence_length
469
uniprot
proteins
subcellular_location
SUBCELLULAR LOCATION: Cytoplasm {ECO:0000269|PubMed:10932193}. Nucleus {ECO:0000269|PubMed:10932193}. Note=Localized in hippocampal neuron nuclei (By similarity). In spermatids, associated with chromatin and nuclear matrix. {ECO:0000250}.
uniprot
proteins