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

MAPKAPK3 (Q16644) - Overview - Molecular Target Synopsis

Protein


MAPKAPK3, MAP kinase-activated protein kinase 3
Enzyme Classification 2.7.11.1
UniProt Q16644

Also Known as MAPK3_HUMAN, MAPKAPK3

Stress-activated serine/threonine-protein kinase involved in cytokines production, endocytosis, cell migration, chromatin remodeling and transcriptional regulation. Following stress, it is phosphorylated and activated by MAP kinase p38-alpha/MAPK14, leading to phosphorylation of substrates. Phosphorylates serine in the peptide sequence, Hyd-X-R-X(2)-S, where Hyd is a large hydrophobic residue. MAPKAPK2 and MAPKAPK3, share the same function and substrate specificity, but MAPKAPK3 kinase activity and level in protein expression are lower compared to MAPKAPK2. Phosphorylates HSP27/HSPB1, KRT18, KRT20, RCSD1, RPS6KA3, TAB3 and TTP/ZFP36. Mediates phosphorylation of HSP27/HSPB1 in response to stress, leading to dissociate HSP27/HSPB1 from large small heat-shock protein (sHsps) oligomers and impair their chaperone activities and ability to protect against oxidative stress effectively. Involved in inflammatory response by regulating tumor necrosis factor (TNF) and IL6 production post-transcriptionally: acts by phosphorylating AU-rich elements (AREs)-binding proteins, such as TTP/ZFP36, leading to regulate the stability and translation of TNF and IL6 mRNAs. Phosphorylation of TTP/ZFP36, a major post-transcriptional regulator of TNF, promotes its binding to 14-3-3 proteins and reduces its ARE mRNA affinity leading to inhibition of dependent degradation of ARE-containing transcript. Involved in toll-like receptor signaling pathway (TLR) in dendritic cells: required for acute TLR-induced macropinocytosis by phosphorylating and activating RPS6KA3. Also acts as a modulator of Polycomb-mediated repression. Heterodimer with p38-alpha/MAPK14. The heterodimer with p38-alpha/MAPK14 forms a stable complex: molecules are positioned 'face to face' so that the ATP-binding sites of both kinases are at the heterodimer interface (By similarity). Interacts with TCF3 and with polycomb proteins, such as PCH2 and BMI1/PCGF4.

3SHE
NOVEL ATP-COMPETITIVE MK2 INHIBITORS WITH POTENT BIOCHEMICAL AND CELL- BASED ACTIVITY THROUGHOUT THE SERIES
RCSB/PDB
Inspect Structure
See all 3D Structures for MAPKAPK3

Isoforms / Transcripts (Protein Coding)


Sub-cellular localization


UniProt: MAPKAPK3 is active in the following subcellular-locations: cytoplasm, nucleus.
GO terms: MAPKAPK3 is active in the following subcellular-locations: cytoplasm, cytosol, nucleoplasm, nucleus.



UniProt
GO terms

Gene Copy Number Variation


In COSMIC - Cell Lines Project MAPKAPK3 has gain in 0 cell-lines, loss in 8 cell-lines and no signal in 997 cell-lines. (see details)

Gene Expression


In NCI60, the highest expressing cell lines are: PC_3, HL_60, 786_0

In Array Express (RNA-seq of 675 commonly used human cancer cell lines), the highest expressing cell lines are: KG-1, HEL, SKM-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: HMEC, HSMM, NHEK

(see details)

RNA Interference


MAPKAPK3 was reported in the following RNAI studies:

Cell - Large Scale Profiling of Kinase Dependencies in Cancer Cell Lines, the highest RNAi cell lines are: NY, HUO9. (see details)

3D Structures


For MAPKAPK3 there are:
4 structures (4 chains) solved
4 are solved in complex with at least one small molecule ligand



(see details)
Molecular Target 3D Synopsis

Screening and Chemistry


MAPKAPK3 has been screened with 790 compounds (1374 bioactivities), 5 compounds have bioactivities that show binding affinity of <= 500nM (6 bioactivities). (see details)