MAPK8 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 is activated by various cell stimuli, and targets specific transcription factors, and thus mediates immediate-early gene expression in response to cell stimuli. The activation of this kinase by tumor-necrosis factor alpha (TNF-alpha) is found to be required for TNF-alpha induced apoptosis. This kinase is also involved in UV radiation induced apoptosis, which is thought to be related to cytochrom c-mediated cell death pathway. Studies of the mouse counterpart of this gene suggested that this kinase play a key role in T cell proliferation, apoptosis and differentiation. Several alternatively spliced transcript variants encoding distinct isoforms have been reported. [provided by RefSeq, Apr 2016]

MAPK8 (Mitogen-Activated Protein Kinase 8) is a Protein Coding gene. Diseases associated with MAPK8 include Fatty Liver Disease and Hepatitis C. Among its related pathways are ATM Pathway and Association Between Physico-Chemical Features and Toxicity Associated Pathways. 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 MAPK8/JNK1. In turn, MAPK8/JNK1 phosphorylates a number of transcription factors, primarily components of AP-1 such as JUN, JDP2 and ATF2 and thus regulates AP-1 transcriptional activity. Phosphorylates the replication licensing factor CDT1, inhibiting the interaction between CDT1 and the histone H4 acetylase HBO1 to replication origins. Loss of this interaction abrogates the acetylation required for replication initiation. Promotes stressed cell apoptosis by phosphorylating key regulatory factors including p53/TP53 and Yes-associates protein YAP1. In T-cells, MAPK8 and MAPK9 are required for polarized differentiation of T-helper cells into Th1 cells. Contributes to the survival of erythroid cells by phosphorylating the antagonist of cell death BAD upon EPO stimulation. Mediates starvation-induced BCL2 phosphorylation, BCL2 dissociation from BECN1, and thus activation of autophagy. Phosphorylates STMN2 and hence regulates microtubule dynamics, controlling neurite elongation in cortical neurons. In the developing brain, through its cytoplasmic activity on STMN2, negatively regulates the rate of exit from multipolar stage and of radial migration from the ventricular zone. Phosphorylates several other substrates including heat shock factor protein 4 (HSF4), the deacetylase SIRT1, ELK1, or the E3 ligase ITCH. Phosphorylates the CLOCK-ARNTL/BMAL1 heterodimer and plays a role in the regulation of the circadian clock (PubMed:22441692). Phosphorylates the heat shock transcription factor HSF1, suppressing HSF1-induced transcriptional activity (PubMed:10747973). Phosphorylates POU5F1, which results in the inhibition of POU5F1's transcriptional activity and enhances its proteosomal degradation (By similarity). Phosphorylates JUND and this phosphorylation is inhibited in the presence of MEN1 (By similarity). In neurons, phosphorylates SYT4 which captures neuronal dense core vesicles at synapses (By similarity).

  • MK08_HUMAN,P45983
• JNK1 isoforms display different binding patterns: beta-1 preferentially binds to c-Jun, whereas alpha-1, alpha-2, and beta-2 have a similar low level of binding to both c-Jun or ATF2. However, there is no correlation between binding and phosphorylation, which is achieved at about the same efficiency by all isoforms.

  • MK08_HUMAN,P45983

• 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(6881)
• Entrez Gene(5599)
• Ensembl(ENSG00000107643)
• OMIM(601158)
• UniProtKB(P45983)
• Open Targets Platform(ENSG00000107643)
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• Monarch Initiative
• Search for MAPK8 at DataMed
• Search for MAPK8 at HumanCyc

No data available for CIViC Summary , PharmGKB "VIP" Summary , Rfam classification and piRNA Summary for MAPK8 Gene

No data available for Human Phenotype Ontology , Transcription Factor Targets and HOMER Transcription for MAPK8 Gene

Subcellular locations from UniProtKB/Swiss-Prot for MAPK8 Gene

No data available for Subcellular locations from the Human Protein Atlas (HPA) for MAPK8 Gene

No data available for mRNA differential expression in normal tissues , Protein tissue co-expression partners , mRNA Expression by UniProt/SwissProt and Phenotype-based relationships between genes and organs from Gene ORGANizer for MAPK8 Gene

No data available for Polymorphic Variants from UniProtKB/Swiss-Prot for MAPK8 Gene

No data available for UniProtKB/Swiss-Prot and Genatlas for MAPK8 Gene

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