MAPK9 Gene (Protein Coding)

• The protein encoded by this gene is a member of the MAP kinase family. MAP kinases act as an integration point for multiple biochemical signals, and are involved in a wide variety of cellular processes such as proliferation, differentiation, transcription regulation and development. This kinase targets specific transcription factors, and thus mediates immediate-early gene expression in response to various cell stimuli. It is most closely related to MAPK8, both of which are involved in UV radiation induced apoptosis, thought to be related to the cytochrome c-mediated cell death pathway. This gene and MAPK8 are also known as c-Jun N-terminal kinases. This kinase blocks the ubiquitination of tumor suppressor p53, and thus it increases the stability of p53 in nonstressed cells. Studies of this gene's mouse counterpart suggest a key role in T-cell differentiation. Several alternatively spliced transcript variants encoding distinct isoforms have been reported. [provided by RefSeq, Sep 2008]

MAPK9 (Mitogen-Activated Protein Kinase 9) is a Protein Coding gene. Diseases associated with MAPK9 include Breast Cancer and Pheochromocytoma. Among its related pathways are GDNF-Family Ligands and Receptor Interactions and NGF Pathway. Gene Ontology (GO) annotations related to this gene include transferase activity, transferring phosphorus-containing groups and protein tyrosine kinase activity. An important paralog of this gene is MAPK10.

• 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 (By similarity).

  • MK09_HUMAN,P45984
• 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.

  • MK09_HUMAN,P45984

• JNKs (c-Jun N-terminal kinases) are a group of mitogen-activated protein kinases (MAPKs), originally called stress activated protein kinases (SAPKs), because they are activated by various environmental stresses. They can also be activated by cytokines and growth factors.

• HGNC(6886)
• Entrez Gene(5601)
• Ensembl(ENSG00000050748)
• OMIM(602896)
• UniProtKB(P45984)
• Open Targets Platform(ENSG00000050748)
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• Monarch Initiative
• Search for MAPK9 at DataMed
• Search for MAPK9 at HumanCyc

No data available for CIViC Summary , PharmGKB "VIP" Summary , Rfam classification and piRNA Summary for MAPK9 Gene

No data available for Human Phenotype Ontology , Transcription Factor Targets and HOMER Transcription for MAPK9 Gene

Subcellular locations from UniProtKB/Swiss-Prot for MAPK9 Gene

No data available for Subcellular locations from the Human Protein Atlas (HPA) for MAPK9 Gene

No data available for mRNA expression in embryonic tissues and stem cells from LifeMap Discovery , mRNA differential expression in normal tissues , mRNA Expression by UniProt/SwissProt and Phenotype-based relationships between genes and organs from Gene ORGANizer for MAPK9 Gene

No data available for Polymorphic Variants from UniProtKB/Swiss-Prot for MAPK9 Gene