ID:KCC4_HUMAN DESCRIPTION: RecName: Full=Calcium/calmodulin-dependent protein kinase type IV; Short=CaMK IV; EC=2.7.11.17; AltName: Full=CaM kinase-GR; 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 consodilation. 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 osteolclasts and dendritic cells (DCs). Mediates DCs survival by linking TLR4 and the regulation of temporal expression of BCL2. Phosphrylates 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: 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. SUBUNIT: Monomer (By similarity). Interacts with protein phosphatase 2A (PPP2CA/PPP2CB); the interaction is mutually exclusive with binding to Ca(2+)/calmodulin. SUBCELLULAR LOCATION: Cytoplasm. Nucleus. Note=Localized in hippocampal neuron nuclei. In spermatids, associated with chromatin and nuclear matrix (By similarity). TISSUE SPECIFICITY: Expressed in brain, thymus, CD4 T-cells, testis and epithelial ovarian cancer tissue. DEVELOPMENTAL STAGE: Expressed during differentiation of monocyte- derived dendritic cells (at protein level). DOMAIN: The autoinhibitory domain overlaps with the calmodulin binding region and interacts in the inactive folded state with the catalytic domain as a pseudosubstrate. PTM: Phosphorylated by CaMKK1 and CaMKK2 on Thr-200. Dephosphorylated by protein phosphatase 2A. Autophosphorylated on Ser-12 and Ser-13. 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. SIMILARITY: Belongs to the protein kinase superfamily. CAMK Ser/Thr protein kinase family. CaMK subfamily. SIMILARITY: Contains 1 protein kinase domain. SEQUENCE CAUTION: Sequence=AAH16695.2; Type=Erroneous initiation; Note=Translation N-terminally shortened;
The RNAfold program from the Vienna RNA Package is used to perform the secondary structure predictions and folding calculations. The estimated folding energy is in kcal/mol. The more negative the energy, the more secondary structure the RNA is likely to have.
ModBase Predicted Comparative 3D Structure on Q16566
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Orthologous Genes in Other Species
Orthologies between human, mouse, and rat are computed by taking the best BLASTP hit, and filtering out non-syntenic hits. For more distant species reciprocal-best BLASTP hits are used. Note that the absence of an ortholog in the table below may reflect incomplete annotations in the other species rather than a true absence of the orthologous gene.
LP896353 - Sequence 1217 from Patent EP3253886. L24959 - Human calcium/calmodulin dependent protein kinase mRNA, complete cds. AK311662 - Homo sapiens cDNA, FLJ18704. AK312840 - Homo sapiens cDNA, FLJ93281, highly similar to Homo sapiens calcium/calmodulin-dependent protein kinase IV (CAMK4), mRNA. BC025687 - Homo sapiens calcium/calmodulin-dependent protein kinase IV, mRNA (cDNA clone MGC:36771 IMAGE:5205478), complete cds. BC016695 - Homo sapiens calcium/calmodulin-dependent protein kinase IV, mRNA (cDNA clone IMAGE:4104268), partial cds. D30742 - Homo sapiens mRNA for calmodulin-dependent protein kinase IV, complete cds. L17000 - Homo sapiens calcium/calmodulin-dependent protein kinase mRNA, complete cds. CU677679 - Synthetic construct Homo sapiens gateway clone IMAGE:100019564 5' read CAMK4 mRNA. AB529005 - Synthetic construct DNA, clone: pF1KE0951, Homo sapiens CAMK4 gene for calcium/calmodulin-dependent protein kinase IV, without stop codon, in Flexi system. DQ896523 - Synthetic construct Homo sapiens clone IMAGE:100010983; FLH195151.01L; RZPDo839A0384D calcium/calmodulin-dependent protein kinase IV (CAMK4) gene, encodes complete protein. DQ896524 - Synthetic construct Homo sapiens clone IMAGE:100010984; FLH195152.01L; RZPDo839B0384D calcium/calmodulin-dependent protein kinase IV (CAMK4) gene, encodes complete protein. DQ896525 - Synthetic construct Homo sapiens clone IMAGE:100010985; FLH195153.01L; RZPDo839C0384D calcium/calmodulin-dependent protein kinase IV (CAMK4) gene, encodes complete protein. DQ896526 - Synthetic construct Homo sapiens clone IMAGE:100010986; FLH195154.01L; RZPDo839D0384D calcium/calmodulin-dependent protein kinase IV (CAMK4) gene, encodes complete protein. DQ892902 - Synthetic construct clone IMAGE:100005532; FLH195157.01X; RZPDo839G0384D calcium/calmodulin-dependent protein kinase IV (CAMK4) gene, encodes complete protein. DQ893195 - Synthetic construct clone IMAGE:100005825; FLH195155.01X; RZPDo839E0384D calcium/calmodulin-dependent protein kinase IV (CAMK4) gene, encodes complete protein. DQ893196 - Synthetic construct clone IMAGE:100005826; FLH195156.01X; RZPDo839F0384D calcium/calmodulin-dependent protein kinase IV (CAMK4) gene, encodes complete protein. KJ896535 - Synthetic construct Homo sapiens clone ccsbBroadEn_05929 CAMK4 gene, encodes complete protein. KJ905156 - Synthetic construct Homo sapiens clone ccsbBroadEn_14561 CAMK4 gene, encodes complete protein. AL833368 - Homo sapiens mRNA; cDNA DKFZp667F2314 (from clone DKFZp667F2314). JD447486 - Sequence 428510 from Patent EP1572962. JD345303 - Sequence 326327 from Patent EP1572962. JD507895 - Sequence 488919 from Patent EP1572962. JD167517 - Sequence 148541 from Patent EP1572962. JD517297 - Sequence 498321 from Patent EP1572962.
Biochemical and Signaling Pathways
BioCarta from NCI Cancer Genome Anatomy Project h_pgc1aPathway - Regulation of PGC-1a h_nfatPathway - NFAT and Hypertrophy of the heart (Transcription in the broken heart) h_CaCaMPathway - Ca++/ Calmodulin-dependent Protein Kinase Activation h_stathminPathway - Stathmin and breast cancer resistance to antimicrotubule agents
Reactome (by CSHL, EBI, and GO)
Protein Q16566 (Reactome details) participates in the following event(s):
US Server
Sequence and Links to Tools and Databases 
Common Gene Haplotype Alleles 
