Molecular Target Synopsis
Overview
Domains and Structures
Drugs and Clinical Candidates
Druggability
Chemistry
Ligand Efficiency Plot
Pathways
Family Cladogram
Interaction Network
Gene Expression
Gene Copy Number Variation
RNAi
Mutations
Germline Genetics

CAMK4 (Q16566) - Overview - Molecular Target Synopsis

Protein


CAMK4, Calcium/calmodulin-dependent protein kinase type IV
Enzyme Classification 2.7.11.17
UniProt Q16566

Also Known as KCC4_HUMAN, CAMK4, CAMK, CAMK-GR, CAMKIV

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. Monomer (By similarity). Interacts with protein phosphatase 2A (PPP2CA/PPP2CB); the interaction is mutually exclusive with binding to Ca(2+)/calmodulin.

2W4O
CRYSTAL STRUCTURE OF HUMAN CAMK4 IN COMPLEX WITH 4-AMINO(SULFAMOYL- PHENYLAMINO)-TRIAZOLE-CARBOTHIOIC ACID (2,6-DIFLUORO-PHENYL)-AMIDE)
RCSB/PDB
Inspect Structure
See all 3D Structures for CAMK4

Isoforms / Transcripts (Protein Coding)


Sub-cellular localization


UniProt: CAMK4 is active in the following subcellular-locations: cytoplasm, nucleus.
GO terms: CAMK4 is active in the following subcellular-locations: cytoplasm, cytosol, extracellular exosome, fibrillar center, glutamatergic synapse, nucleoplasm, nucleus, postsynapse.



UniProt
GO terms

Gene Copy Number Variation


In COSMIC - Cell Lines Project CAMK4 has gain in 2 cell-lines, loss in 2 cell-lines and no signal in 1001 cell-lines. (see details)

Gene Expression


In NCI60, the highest expressing cell lines are: SK_MEL_28, SK_MEL_5, BT_549

In Array Express (RNA-seq of 675 commonly used human cancer cell lines), the highest expressing cell lines are: Pfeiffer, Jurkat, Clone E6-1, MHH-PREB-1

In Array Express (RNA-seq of long poly adenylated RNA and long non poly adenylated RNA from ENCODE cell lines), the highest expressing cell lines are: GM12878, SK-N-SH, HSMM

(see details)

RNA Interference


CAMK4 was reported in the following RNAI studies:

Cell - Large Scale Profiling of Kinase Dependencies in Cancer Cell Lines, the highest RNAi cell lines are: MHM, HUO3N1. (see details)

3D Structures


For CAMK4 there are:
1 structures (1 chains) solved
1 are solved in complex with at least one small molecule ligand



(see details)
Molecular Target 3D Synopsis

Screening and Chemistry


CAMK4 has been screened with 934 compounds (1598 bioactivities), 4 compounds have bioactivities that show binding affinity of <= 500nM (5 bioactivities). (see details)