Mitogen-activated protein kinase 9

UniProt P45984 Organism Homo sapiens Gene JNK2, MAPK9, PRKM9, SAPK1A EC 2.7.11.24

Also known as: JNK2, MAPK9, PRKM9, SAPK1A

Function

Serine/threonine-protein kinase involved in various processes such as cell proliferation, differentiation, migration, transformation and programmed cell death. Extracellular stimuli such as pro-inflammatory 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. Also participates in neurite growth in spiral ganglion neurons (By similarity). Phosphorylates the CLOCK-BMAL1 heterodimer and plays a role in the regulation of the circadian clock. Phosphorylates POU5F1, which results in the inhibition of POU5F1's transcriptional activity and enhances its proteasomal degradation (By similarity). Phosphorylates ALKBH5 in response to reactive oxygen species (ROS), promoting ALKBH5 sumoylation and inactivation.

Classification

Family (Pfam): PF00069 Pkinase
InterPro: Kinase-like_dom_sf, MAP_kinase_CS, MAPK, MAPK_JNK, Prot_kinase_dom, Ser/Thr_kinase_AS
Functional cluster: Phosphoribosyltransferases & related

Experimental structures · PDB · 5

3E7O X-ray 2.14A
3NPC X-ray 2.35A
7CML X-ray 2.15A
7N8T X-ray 1.69A
8ELC X-ray 2.07A

A predicted model is available from AlphaFold.

Gene Ontology · 26

Drugs targeting this protein · 3

CC-401 inhibitor
TANZISERTIB inhibitor
BENTAMAPIMOD inhibitor

Related proteins · sequence + function similarity

Co-cited proteins · studied together in the literature

Mitogen-activated protein kinase 10 4 shared papers
RNA polymerase I-specific transcription initiation factor RRN3 1 shared papers
Mitogen-activated protein kinase 8 7 shared papers
WD repeat-containing protein 62 2 shared papers
Mitogen-activated protein kinase-binding protein 1 2 shared papers
Cyclic AMP-dependent transcription factor ATF-7 1 shared papers
Nuclear factor of activated T-cells, cytoplasmic 4 1 shared papers
C-Jun-amino-terminal kinase-interacting protein 4 1 shared papers
RNA demethylase ALKBH5 1 shared papers
Transcription factor Jun 1 shared papers
Transcriptional coactivator YAP1 1 shared papers
Mitogen-activated protein kinase 10 1 shared papers

Literature · 27 cited papers

Post-translational modification of RNA m6A demethylase ALKBH5 regulates ROS-induced DNA damage response. Nucleic Acids Res. · 2021
PMID 28157543 Am. J. Hum. Genet. · 2017
Mutations in MAPKBP1 cause juvenile or late-onset cilia-independent nephronophthisis. Am. J. Hum. Genet. · 2017
JNK regulates the photic response of the mammalian circadian clock. EMBO Rep. · 2012
JNK phosphorylates Yes-associated protein (YAP) to regulate apoptosis. Cell Death Dis. · 2010
Initial characterization of the human central proteome. BMC Syst. Biol. · 2011
Molecular cloning and characterization of novel human JNK2 (MAPK9) transcript variants that show different stimulation activities on AP-1. BMB Rep. · 2010
c-Jun NH2-terminal kinase-2 mediates osmotic stress-induced tight junction disruption in the intestinal epithelium. Am. J. Physiol. · 2010
GSK3beta is involved in JNK2-mediated beta-catenin inhibition. PLoS ONE · 2009
Large-scale proteomics analysis of the human kinome. Mol. Cell. Proteomics · 2009
CARMA1-mediated NF-kappaB and JNK activation in lymphocytes. Immunol. Rev. · 2009
Human protein factory for converting the transcriptome into an in vitro-expressed proteome. Nat. Methods · 2008
… and 15 more in the literature graph

A document in the lmmol reference corpus — open public data (UniProt, GO, PDB, the literature graph) rendered as a single cross-linked page. Hover any link to preview its target.