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

MAPKAPK2 (P49137) - Overview - Molecular Target Synopsis

Protein


MAPKAPK2, MAP kinase-activated protein kinase 2
Enzyme Classification 2.7.11.1
UniProt P49137

Also Known as MAPK2_HUMAN, MAPKAPK2

Stress-activated serine/threonine-protein kinase involved in cytokine production, endocytosis, reorganization of the cytoskeleton, cell migration, cell cycle control, chromatin remodeling, DNA damage response 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. Phosphorylates ALOX5, CDC25B, CDC25C, CEP131, ELAVL1, HNRNPA0, HSP27/HSPB1, KRT18, KRT20, LIMK1, LSP1, PABPC1, PARN, PDE4A, RCSD1, RPS6KA3, TAB3 and TTP/ZFP36. Phosphorylates HSF1; leading to the interaction with HSP90 proteins and inhibiting HSF1 homotrimerization, DNA-binding and transactivation activities (PubMed:16278218). Mediates phosphorylation of HSP27/HSPB1 in response to stress, leading to the dissociation of HSP27/HSPB1 from large small heat-shock protein (sHsps) oligomers and impairment of 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 ELAVL1, HNRNPA0, PABPC1 and TTP/ZFP36, leading to the regulation of 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 transcripts. Phosphorylates CEP131 in response to cellular stress induced by ultraviolet irradiation which promotes binding of CEP131 to 14-3-3 proteins and inhibits formation of novel centriolar satellites (PubMed:26616734). Also involved in late G2/M checkpoint following DNA damage through a process of post-transcriptional mRNA stabilization: following DNA damage, relocalizes from nucleus to cytoplasm and phosphorylates HNRNPA0 and PARN, leading to stabilization of GADD45A mRNA. Involved in toll-like receptor signaling pathway (TLR) in dendritic cells: required for acute TLR-induced macropinocytosis by phosphorylating and activating RPS6KA3. Heterodimer with p38-alpha/MAPK14; this heterodimer forms a stable complex: molecules are positioned 'face to face' so that the ATP-binding sites of both kinases are at the heterodimer interface (PubMed:12171911, PubMed:17576063, PubMed:17255097, PubMed:17480064, PubMed:17449059, PubMed:17395714). Interacts with PHC2 (PubMed:15094067). Interacts with HSF1 (PubMed:16278218).

4TYH
TERNARY COMPLEX OF P38 AND MK2 WITH A P38 INHIBITOR
RCSB/PDB
Inspect Structure
See all 3D Structures for MAPKAPK2

Isoforms / Transcripts (Protein Coding)


Protein Length Ensembl Gene Ensembl Transcript Ensembl Protein Uniprot Isoform
400ENSG00000162889ENST00000367103ENSP00000356070P49137-1
370ENSG00000162889ENST00000294981ENSP00000294981P49137-2

Sub-cellular localization


UniProt: MAPKAPK2 is active in the following subcellular-locations: cytoplasm, nucleus.
GO terms: MAPKAPK2 is active in the following subcellular-locations: centrosome, cytoplasm, cytosol, extracellular exosome, nucleoplasm, nucleus.



UniProt
GO terms

Gene Copy Number Variation


In COSMIC - Cell Lines Project MAPKAPK2 has gain in 3 cell-lines, loss in 1 cell-lines and no signal in 1001 cell-lines. (see details)

Gene Expression


In NCI60, the highest expressing cell lines are: SR, MDA_MB_231, HS578T

In Array Express (RNA-seq of 675 commonly used human cancer cell lines), the highest expressing cell lines are: NCI-H929, HCC4011, NCI-H810

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: SK-N-SH, HSMM, NHLF

(see details)

RNA Interference


MAPKAPK2 was reported in the following RNAI studies:

Cell - Large Scale Profiling of Kinase Dependencies in Cancer Cell Lines, the highest RNAi cell lines are: KNS42, SUM149. (see details)

3D Structures


For MAPKAPK2 there are:
25 structures (94 chains) solved
20 are solved in complex with at least one small molecule ligand



(see details)
Molecular Target 3D Synopsis

Screening and Chemistry


MAPKAPK2 has been screened with 2388 compounds (3489 bioactivities), 445 compounds have bioactivities that show binding affinity of <= 500nM (540 bioactivities). (see details)