CAMK4
entrez
814
canonical
uniprot
Q16566
canonical
ensembl
ENSG00000152495
resolver
ensp
ENSP00000282356
resolver
ensp
ENSP00000422634
resolver
ensp
ENSP00000625516
resolver
enst
ENST00000282356
resolver
enst
ENST00000512453
resolver
enst
ENST00000955457
resolver
genesymbol
CAMK4
resolver
genesymbol_syn
CAMK
resolver
genesymbol_syn
CAMK-GR
resolver
genesymbol_syn
CAMKIV
resolver
hgnc
HGNC:1464
resolver
uniprot
D3DSZ7
resolver
uniprot_entry
KCC4_HUMAN
resolver
uniprot_sec
D3DSZ7
resolver
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-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. {ECO:0000269|PubMed:15143065, ECO:0000269|PubMed:15769749, ECO:0000269|PubMed:8702940}.
uniprot
proteins
amino_acid_sequence
MLKVTVPSCSASSCSSVTASAAPGTASLVPDYWIDGSNRDALSDFFEVESELGRGATSIVYRCKQKGTQKPYALKVLKKTVDKKIVRTEIGVLLRLSHPNIIKLKEIFETPTEISLVLELVTGGELFDRIVEKGYYSERDAADAVKQILEAVAYLHENGIVHRDLKPENLLYATPAPDAPLKIADFGLSKIVEHQVLMKTVCGTPGYCAPEILRGCAYGPEVDMWSVGIITYILLCGFEPFYDERGDQFMFRRILNCEYYFISPWWDEVSLNAKDLVRKLIVLDPKKRLTTFQALQHPWVTGKAANFVHMDTAQKKLQEFNARRKLKAAVKAVVASSRLGSASSSHGSIQESHKASRDPSPIQDGNEDMKAIPEGEKIQGDGAQAAVKGAQAELMKVQALEKVKGADINAEEAPKMVPKAVEDGIKVADLELEEGLAEEKLKTVEEAAAPREGQGSSAVGFEVPQQDVILPEY
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. {ECO:0000269|PubMed:10617605, ECO:0000269|PubMed:17909078, ECO:0000269|PubMed:18829949, ECO:0000269|PubMed:7961813, ECO:0000269|PubMed:8065343, ECO:0000269|PubMed:8855261, ECO:0000269|PubMed:8980227, ECO:0000269|PubMed:9154845}.
uniprot
proteins
mass_dalton
51926
uniprot
proteins
mutagenesis
MUTAGEN 12; /note="S->A: Loss of activity."; /evidence="ECO:0000269|PubMed:8702940"; MUTAGEN 13; /note="S->A: Loss of activity."; /evidence="ECO:0000269|PubMed:8702940"; MUTAGEN 57..58; /note="TS->AA: Loss of phosphorylation of CREB1."; /evidence="ECO:0000269|PubMed:19506079"; MUTAGEN 75; /note="K->E: Loss of activity; dominant negative form."; /evidence="ECO:0000269|PubMed:10617605"; MUTAGEN 189; /note="S->A: Increases phosphorylation of CREB1 2-fold. Decreases total O-linked glycosylation 2-fold. Increases ATP-binding affinity."; /evidence="ECO:0000269|PubMed:19506079"; MUTAGEN 200; /note="T->A: Loss of activation by CaMKK1 or CaMKK2."; /evidence="ECO:0000269|PubMed:8855261"; MUTAGEN 309..312; /note="HMDT->DEDD: Fully active Ca2+/CaM-independent kinase; when associated with 320-A-A-321."; /evidence="ECO:0000269|PubMed:7961813"; MUTAGEN 320..321; /note="FN->DD: Fully active Ca2+/CaM-independent kinase; when associated with 309-A--A-312. Loss of interaction with PPP2CA/PPP2CB."; /evidence="ECO:0000269|PubMed:15143065, ECO:0000269|PubMed:7961813
uniprot
proteins
post_translational_modification
PTM: Phosphorylated by CaMKK1 and CaMKK2 on Thr-200. Dephosphorylated by protein phosphatase 2A. Autophosphorylated on Ser-12 and Ser-13. {ECO:0000269|PubMed:15143065, ECO:0000269|PubMed:19506079, ECO:0000269|PubMed:8702940}.; PTM: 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. {ECO:0000269|PubMed:15143065, ECO:0000269|PubMed:19506079, ECO:0000269|PubMed:8702940}.
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
10617605
uniprot
proteins
pubmed
12065094
uniprot
proteins
pubmed
15143065
uniprot
proteins
pubmed
15489334
uniprot
proteins
pubmed
15769749
uniprot
proteins
pubmed
17344846
uniprot
proteins
pubmed
17909078
uniprot
proteins
pubmed
18817731
uniprot
proteins
pubmed
18829949
uniprot
proteins
pubmed
18930438
uniprot
proteins
pubmed
19413330
uniprot
proteins
pubmed
19506079
uniprot
proteins
pubmed
19690332
uniprot
proteins
pubmed
21269460
uniprot
proteins
pubmed
24275569
uniprot
proteins
pubmed
7961813
uniprot
proteins
pubmed
8065343
uniprot
proteins
pubmed
8089075
uniprot
proteins
pubmed
8107230
uniprot
proteins
pubmed
8194751
uniprot
proteins
pubmed
8397199
uniprot
proteins
pubmed
8702940
uniprot
proteins
pubmed
8855261
uniprot
proteins
pubmed
8980227
uniprot
proteins
pubmed
9154845
uniprot
proteins
pubmed
9920409
uniprot
proteins
sequence_length
473
uniprot
proteins
subcellular_location
SUBCELLULAR LOCATION: Cytoplasm. Nucleus. Note=Localized in hippocampal neuron nuclei. In spermatids, associated with chromatin and nuclear matrix (By similarity). {ECO:0000250}.
uniprot
proteins