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

MAPK9 (P45984) - Overview - Molecular Target Synopsis

Protein


MAPK9, Mitogen-activated protein kinase 9
Enzyme Classification 2.7.11.24
UniProt P45984

Also Known as MK09_HUMAN, MAPK9, JNK2, PRKM9, SAPK1A

Serine/threonine-protein kinase involved in various processes such as cell proliferation, differentiation, migration, transformation and programmed cell death. Extracellular stimuli such as proinflammatory cytokines or physical stress stimulate the stress-activated protein kinase/c-Jun N-terminal kinase (SAP/JNK) signaling pathway. In this cascade, two dual specificity kinases MAP2K4/MKK4 and MAP2K7/MKK7 phosphorylate and activate MAPK9/JNK2. In turn, MAPK9/JNK2 phosphorylates a number of transcription factors, primarily components of AP-1 such as JUN and ATF2 and thus regulates AP-1 transcriptional activity. In response to oxidative or ribotoxic stresses, inhibits rRNA synthesis by phosphorylating and inactivating the RNA polymerase 1-specific transcription initiation factor RRN3. Promotes stressed cell apoptosis by phosphorylating key regulatory factors including TP53 and YAP1. In T-cells, MAPK8 and MAPK9 are required for polarized differentiation of T-helper cells into Th1 cells. Upon T-cell receptor (TCR) stimulation, is activated by CARMA1, BCL10, MAP2K7 and MAP3K7/TAK1 to regulate JUN protein levels. Plays an important role in the osmotic stress-induced epithelial tight-junctions disruption. When activated, promotes beta-catenin/CTNNB1 degradation and inhibits the canonical Wnt signaling pathway. Participates also in neurite growth in spiral ganglion neurons. Phosphorylates the CLOCK-ARNTL/BMAL1 heterodimer and plays a role in the regulation of the circadian clock (PubMed:22441692). Phosphorylates POU5F1, which results in the inhibition of POU5F1's transcriptional activity and enhances its proteosomal degradation., MAPK9 isoforms display different binding patterns: alpha-1 and alpha-2 preferentially bind to JUN, whereas beta-1 and beta-2 bind to ATF2. However, there is no correlation between binding and phosphorylation, which is achieved at about the same efficiency by all isoforms. JUNB is not a substrate for JNK2 alpha-2, and JUND binds only weakly to it. Interacts with MECOM (By similarity). Interacts with DCLK2 (By similarity). Binds to at least four scaffolding proteins, MAPK8IP1/JIP-1, MAPK8IP2/JIP-2, MAPK8IP3/JIP-3/JSAP1 and SPAG9/MAPK8IP4/JIP-4. These proteins also bind other components of the JNK signaling pathway (By similarity). Interacts with NFATC4 (PubMed:17875713). Interacts with ATF7; the interaction does not phosphorylate ATF7 but acts as a docking site for ATF7-associated partners such as JUN (PubMed:10376527). Interacts with BCL10 (PubMed:17189706). Interacts with CTNNB1 and GSK3B (PubMed:19675674). Interacts with MAPKBP1 (PubMed:28089251). Interacts with POU5F1; phosphorylates POU5F1 at 'Ser-355'. Found in a complex with SH3RF1, RAC2, MAP3K7/TAK1, MAP2K7/MKK7, MAPK8IP1/JIP1 and MAPK8/JNK1.

3NPC
CRYSTAL STRUCTURE OF JNK2 COMPLEXED WITH BIRB796
RCSB/PDB
Inspect Structure
See all 3D Structures for MAPK9

Isoforms / Transcripts (Protein Coding)


Sub-cellular localization


UniProt: MAPK9 is active in the following subcellular-locations: cytoplasm, nucleus.
GO terms: MAPK9 is active in the following subcellular-locations: cytoplasm, cytosol, mitochondrion, neuron projection, nucleoplasm, nucleus.



UniProt
GO terms

Gene Copy Number Variation


In COSMIC - Cell Lines Project MAPK9 has gain in 3 cell-lines, loss in 2 cell-lines and no signal in 1000 cell-lines. (see details)

Gene Expression


In NCI60, the highest expressing cell lines are: SF_268, HOP_62, NCI_H522

In Array Express (RNA-seq of 675 commonly used human cancer cell lines), the highest expressing cell lines are: HCC1954, SW 1573, CaR-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: HSMM, NHLF, SK-N-SH

(see details)

RNA Interference


MAPK9 was reported in the following RNAI studies:

Cell - Large Scale Profiling of Kinase Dependencies in Cancer Cell Lines, the highest RNAi cell lines are: CAL51, H23. (see details)

3D Structures


For MAPK9 there are:
2 structures (4 chains) solved
2 are solved in complex with at least one small molecule ligand



(see details)
Molecular Target 3D Synopsis

Screening and Chemistry


MAPK9 has been screened with 1967 compounds (2958 bioactivities), 359 compounds have bioactivities that show binding affinity of <= 500nM (443 bioactivities). (see details)